|Shouichi Ohga||Last modified date：2021.07.15|
Professor / Department of Clinical Medicine / Faculty of Medical Sciences
|Shouichi Ohga||Last modified date：2021.07.15|
|1.||Ryoji Taira, Hirosuke Inoue, Toru Sawano, Junko Fujiyoshi, Yuko Ichimiya, Michiko Torio, Masafumi Sanefuji, Masayuki Ochiai, Yasunari Sakai, Shouichi Ohga, Management of apnea in infants with trisomy 18., Developmental medicine and child neurology, 10.1111/dmcn.14403, 62, 7, 874-878, 2020.07, This case series aimed to characterize the clinical features, management, and outcomes of apnea in infants with trisomy 18. Participants in this study were infants with trisomy 18 who were born alive and admitted to the neonatal intensive care unit in Kyushu University Hospital from 2000 to 2018. Retrospective analysis was performed on clinical data recorded in our department. Twenty-seven infants with trisomy 18 were admitted to our hospital during the study period, of which 25 (nine males, 16 females) were enrolled as eligible participants in this study. Among them, 14 started presenting with apnea from median 3.5 days of age (range 0-47d). In these infants with apnea, eight received respiratory support of positive pressure ventilation (PPV). The 1-year survival rate of infants in the PPV group was higher than that of non-PPV-supported infants (5 out of 8 vs 0 out of 6 infants). Five PPV-supported infants received a diagnosis of epilepsy, which was controlled by antiepileptic drugs. Postnatal respiratory intervention provides better prognosis in infants with trisomy 18. Improved survival leads to accurate diagnosis and treatment of apneic events in association with epilepsy. WHAT THIS PAPER ADDS: Respiratory support is effective against apnea in infants with trisomy 18. Intervention with ventilation provides a higher chance of prolonged survival. Improved survival leads to the accurate diagnosis and treatment of epilepsy-associated apnea..|
|2.||Tsuyoshi Iwanaka, Takayoshi Yamaza, Soichiro Sonoda, Koichiro Yoshimaru, Toshiharu Matsuura, Haruyoshi Yamaza, Shouichi Ohga, Yoshinao Oda, Tomoaki Taguchi, A model study for the manufacture and validation of clinical-grade deciduous dental pulp stem cells for chronic liver fibrosis treatment, Stem Cell Research and Therapy, 10.1186/s13287-020-01630-w, 11, 1, 2020.03, Background: Human deciduous pulp stem cells (hDPSCs) have remarkable stem cell potency associated with cell proliferation, mesenchymal multipotency, and immunosuppressive function and have shown beneficial effects in a variety of animal disease models. Recent studies demonstrated that hDPSCs exhibited in vivo anti-fibrotic and anti-inflammatory action and in vivo hepatogenic-associated liver regeneration, suggesting that hDPSCs may offer a promising source with great clinical demand for treating liver diseases. However, how to manufacture ex vivo large-scale clinical-grade hDPSCs with the appropriate quality, safety, and preclinical efficacy assurances remains unclear. Methods: We isolated hDPSCs from human deciduous dental pulp tissues formed by the colony-forming unit-fibroblast (CFU-F) method and expanded them under a xenogeneic-free and serum-free (XF/SF) condition; hDPSC products were subsequently stored by two-step banking including a master cell bank (MCB) and a working cell bank (WCB). The final products were directly thawed hDPSCs from the WCB. We tested the safety and quality check, stem cell properties, and preclinical potentials of final hDPSC products and hDPSC products in the MCB and WCB. Results: We optimized manufacturing procedures to isolate and expand hDPSC products under a XF/SF culture condition and established the MCB and the WCB. The final hDPSC products and hDPSC products in the MCB and WCB were validated the safety and quality including population doubling ability, chromosome stability, microorganism safety, and stem cell properties including morphology, cell surface marker expression, and multipotency. We also evaluated the in vivo immunogenicity and tumorigenicity and validated in vivo therapeutic efficacy for liver regeneration in a CCl4-induced chronic liver fibrosis mouse model in the final hDPSC products and hDPSC products in the WCB. Conclusion: The manufacture and quality control results indicated that the present procedure could produce sufficient numbers of clinical-grade hDPSC products from a tiny deciduous dental pulp tissue to enhance clinical application of hDPSC products in chronic liver fibrosis..|
|3.||Yasunori Iida, Hiroki Yasudo, Reiji Fukano, Yoshihiro Azuma, Takuya Ichimura, Shouichi Ohga, Shunji Hasegawa, Surge of serum interleukin-2 level in a Japanese patient with cytarabine syndrome, Pediatric Blood and Cancer, 10.1002/pbc.28131, 67, 3, 2020.03.|
|4.||Hirofumi Inoue, Takeshi Matsushige, Takashi Ichiyama, Alato Okuno, Osamu Takikawa, Shozo Tomonaga, Banu Anlar, Deniz Yüksel, Yasushi Otsuka, Fumitaka Kohno, Madoka Hoshide, Shouichi Ohga, Shunji Hasegawa, Elevated quinolinic acid levels in cerebrospinal fluid in subacute sclerosing panencephalitis, Journal of Neuroimmunology, 10.1016/j.jneuroim.2019.577088, 339, 2020.02, Subacute sclerosing panencephalitis (SSPE) is a rare neurodegenerative disorder caused by a persistent infection with aberrant measles virus. Indoleamine-2, 3-dioxygenase (IDO) initiates the increased production of kynurenine pathway (KP) metabolites quinolinic acid (QUIN), which has an excitotoxic effect for neurons. We measured serum IDO activity and cerebrospinal fluid (CSF) levels of QUIN. The CSF QUIN levels were significantly higher in SSPE patients than in controls, and increased according as neurological disability in a patient studied. Elevation of CSF QUIN and progression of SSPE indicate a pathological role of KP metabolism in the inflammatory neurodestruction..|
|5.||Ken Fukuda, Hiroki Yasudo, Naoki Ohta, Hiroko Narumi, Nozomi Abe, Shunsuke Tarumoto, Hiroshi Yamashita, Kiyoshi Ichihara, Shouichi Ohga, Shunji Hasegawa, Time-Course Evaluation of Body Mass Index in Japanese Children With Obstructive Sleep Apnea Syndrome After Adenotonsillectomy
A Three-Years Follow-Up Study, Frontiers in Pediatrics, 10.3389/fped.2020.00022, 8, 2020.02, Delayed physical growth is a common complication of pediatric obstructive sleep apnea syndrome (OSAS). Adenotonsillectomy (AT) is the first-line treatment for pediatric OSAS. Only a few studies have performed time-course BMI evaluation in pediatric OSAS patients post-operatively. Thus, we aimed to evaluate the time-course changes in pediatric OSAS patients after AT. Thirty-three children with OSAS who underwent AT were included and divided into two groups on the basis of their BMI z-scores (delayed physical growth group, n = 15; non-delayed physical growth group, n = 18). Clinical records of height and weight were collected before AT and at 6, 12, 24, and 36 months after AT. Changes in the mean BMI z-scores of the two groups were assessed up to 36 months. The mean BMI z-score was significantly increased in the delayed physical growth group at 6 months after AT. In contrast, the increase in mean BMI z-score was not observed in the non-delayed physical growth group. Growth improvement was noted in pediatric OSAS patients with delayed physical growth after AT. Our results suggest that AT is a promising therapy for improving the physical growth of pediatric OSAS patients with such problems..
|6.||Masayuki Ochiai, Hiroaki Kurata, Hirosuke Inoue, Masako Ichiyama, Junko Fujiyoshi, Shinichi Watabe, Takehiko Hiroma, Tomohiko Nakamura, Shouichi Ohga, Transcutaneous blood gas monitoring among neonatal intensive care units in Japan, Pediatrics International, 10.1111/ped.14107, 62, 2, 169-174, 2020.02, Background: This study aimed to investigate the utility of transcutaneous (tc) measurements of partial pressure of oxygen (tcPO2) and carbon dioxide (tcPCO2) monitoring in neonatal intensive care units (NICUs) in Japan. Methods: At the end of 2016,we sent a survey questionnaire on tc monitoring to all 106 NICUs registered with the Japanese Neonatologist Association. The questions included usage, subjects, methods, management, and the practical usefulness of tc monitoring. Results: The questionnaire was returned by 69 NICUs (65.1% of response rate). Seventeen institutions (24.6%) measured both tcPCO2 and tcPO2, and 42 (60.9%) measured tcPCO2 alone. Transcutaneous PCO2 or tcPO2 monitoring was applied for “pre-viable” infants born at 22–23 weeks’ gestational age (18.6% vs 23.5%), and infants of <500 g birthweight (30.5% vs 17.6%). The tcPCO2 and tcPO2 monitoring was started at birth in 49.2% and 70.6% of the newborn infants, respectively. The temperature of the sensor was set at <38°C for tcPCO2 in 54.3% and >42°C for tcPO2 in 58.9% of NICUs. The accuracy for tcPO2 was rated as good in 35.3% or moderate in 64.7%, of institutions but or for tcPCO2 as 1.7% or 93.2%of institutions, respectively. Conclusion: Transcutaneous monitoring was widely, but limitedly, used for preterm infants. The lower temperature of the tcPCO2 sensor compared to that reported in other developed countries might compromise the accuracy but increase the feasibility of tc monitoring in Japan..|
|7.||Takashi Imai, Akira Shiraishi, Kei Nishiyama, Masataka Ishimura, Shouichi Ohga, Lipopolysaccharide-induced monocyte death in a novel ZnF7 domain mutation of TNFAIP3, Journal of Allergy and Clinical Immunology: In Practice, 10.1016/j.jaip.2020.01.026, 2020.01.|
|8.||Noriko Oyama, Kanako Kojima-Ishii, Naoko Toda, Terumichi Matsuo, Vlad Tocan, Kazuhiro Ohkubo, Utako Oba, Yuhki Koga, Nokitaka Setsu, Yuichi Yamada, Kenichi Kohashi, Yasuharu Nakashima, Yoshinao Oda, Kenji Ihara, Shouichi Ohga, Malignant transformation of phosphaturic mesenchymal tumor
A case report and literature review, Clinical Pediatric Endocrinology, 10.1297/cpe.29.69, 29, 2, 69-75, 2020.01, Phosphaturic mesenchymal tumor, mixed connective tissue variant (PMT-MCT) causes tumor-induced osteomalacia (TIO). Most cases follow a benign clinical course, with rare occurrences of malignant transformation. We report a case of malignant PMT-MCT and review previous malignant cases to identify predictive factors for transformation. A 13-yr-old female, who presented with hypophosphatemic rickets, elevated serum intact fibroblast growth factor 23 (FGF23) levels, and a nodule in the back, received a diagnosis of TIO because of the benign PMT histopathology. After resection of the primary tumor, regular imaging analyses did not indicate any relapse. At 17 years of age, a tumor developed in the left leg and increased in size. The resected tumor showed a histopathology of pleomorphic sarcoma positive for the TP53 mutation. Despite amputation of the affected leg, the patient died due to multiple metastases at 18 years of age. A literature review revealed that 14 out of 15 reported malignant PMT-MCT tumors occurred in adults, and found no predictive factors for malignant transformation and treatment outcome. Changes in size or number of the tumors along with intact FGF23 levels have been considered as the only sign of malignant transformation. This pediatric case report and literature review indicate the need for prolonged regular monitoring for PMT-MCT..
|9.||, Kazuko Kudo, Miho Maeda, Nobuhiro Suzuki, Hirokazu Kanegane, Shouichi Ohga, Eiichi Ishii, Yoko Shioda, Toshihiko Imamura, Shinsaku Imashuku, Yukiko Tsunematsu, Mikiya Endo, Akira Shimada, Yuuki Koga, Yoshiko Hashii, Maiko Noguchi, Masami Inoue, Ken Tabuchi, Akira Morimoto, Nationwide retrospective review of hematopoietic stem cell transplantation in children with refractory Langerhans cell histiocytosis, International journal of hematology, 10.1007/s12185-019-02760-5, 111, 1, 137-148, 2020.01, The efficacy of and indications for hematopoietic stem cell transplantation (HSCT) in pediatric Langerhans cell histiocytosis (LCH) remain undetermined. This retrospective study analyzed 30 children with refractory LCH who underwent HSCT in Japan between 1996 and 2014. Eleven patients received a myeloablative conditioning (MAC) regimen, while 19 patients received a reduced-intensity conditioning (RIC) regimen. Among the 26 patients with complete data, 23 patients had risk organ (RO) involvement during clinical course. Disease status at HSCT was no active disease (NAD) (4), active disease-regression (AD-r) (2), active disease-stable (AD-s) (4), and active disease-progressive (AD-p) (16). Seventeen of the 30 patients (57%) were alive with a median follow-up of 433 days (range 9–5307) after HSCT. Death occurred within 3 months after HSCT in eight of 13 patients. RIC and MAC patients were similar in both overall survival (OS) (56.8% vs. 63.6%, respectively, p = 0.789) and failure-free survival (56.8% vs. 54.6%, respectively, p = 0.938). Regarding disease status at HSCT, the six patients with NAD/AD-r experienced better outcomes than the 20 with AD-s/AD-p (5-year OS, 100% vs. 54.5%, respectively, p = 0.040). Disease state at the time of HSCT was the most important prognostic factor..|
|10.||Mitsuru Arima, Masato Akiyama, Kohta Fujiwara, Yujiro Mori, Hirosuke Inoue, Eiko Seki, Takahito Nakama, Shoko Tsukamoto, Masayuki Ochiai, Shouichi Ohga, Koh Hei Sonoda, Neurodevelopmental outcomes following intravitreal bevacizumab injection in Japanese preterm infants with type 1 retinopathy of prematurity, PloS one, 10.1371/journal.pone.0230678, 15, 3, 2020.01, Purpose The purpose of this study was to evaluate neurodevelopmental outcomes in 18-month old (corrected age) preterm infants who received an intravitreal bevacizumab (IVB) injection for the treatment of type 1 retinopathy of prematurity (ROP). Methods In this ten-year retrospective study, we reviewed the medical records of patients who underwent ROP screening at Kyushu University Hospital. Among the patients who received IVB or laser photocoagulation (LPC) for the treatment of type 1 ROP, we included infants whose neurodevelopmental examination (the Kyoto Scale of Psychological Development [KSPD]) results at 18 months corrected age were available. Then, the effect of IVB on the developmental quotient (DQ) in each KSPD domain (Postural-Movement, Cognitive-Adaptive, or Language-Social domain) or the overall DQ was investigated by performing linear regression analysis. Results Out of the 513 patients reviewed, 53 were included in the study. IVB and LPC were performed for 14 and 39 patients, respectively. Administration of IVB was significantly associated with neurodevelopmental delay in the Language-Social domain (p = 0.01). The observed association remained even after adjusting for gestational age and birth weight (p = 0.03). Conclusions Administration of IVB may introduce a risk of developmental impairment of interpersonal relationships, socializations, and/or verbal abilities of preterm children. We recommended that preterm infants who received IVB undergo a neurodevelopmental reassessment during their school years or in adulthood..|
|11.||Motoshi Sonoda, Masataka Ishimura, Katsuhide Eguchi, Akira Shiraishi, Shunsuke Kanno, Noriyuki Kaku, Hirosuke Inoue, Yoshitomo Motomura, Masayuki Ochiai, Yasunari Sakai, Manabu Nakayama, Osamu Ohara, Shouichi Ohga, Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis, International journal of hematology, 10.1007/s12185-019-02738-3, 111, 1, 131-136, 2020.01, Hemophagocytic lymphohistiocytosis (HLH) occurs in neonates with disseminated infection of herpes simplex virus (HSV). Little has been reported on the control of rapid HLH progression. We studied the cytokine profile and genetic basis of two index cases with divergent outcomes after early treatment of type 2 HSV infection. One survivor had fever and elevated serum levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ at diagnosis. The other neonate had no fever or TNF-α production, but significant IL-6 or IFN responses during the treatment course, and died 19 days after birth. Among 16 reported cases of neonatal HSV-HLH including index cases, eight deceased neonates experienced significantly less fever at presentation (p = 0.028), lower platelet counts (p = 0.019), and lower ratios of soluble IL-2 receptor (sIL-2R) to ferritin levels (p = 0.044) than eight survivors. The 100-day overall survival rates were significantly higher in patients with fever (p = 0.004), > 100 × 109/L of platelet counts (p = 0.035) or > 20 of sIL-2R/ferritin ratio at diagnosis (p = 0.004). The first febrile and cytokine responses to HSV infection predict the early outcome of neonatal HSV-HLH..|
|12.||Kenji Murata, Takayuki Hoshina, Sagano Onoyama, Tamami Tanaka, Shunsuke Kanno, Masataka Ishimura, Yuhki Koga, Hideki Nakayama, Shouichi Ohga, Reduction in the number of varicella-zoster virus-specifit-cells in immunocompromised children with varicella, Tohoku Journal of Experimental Medicine, 10.1620/tjem.250.181, 250, 3, 181-190, 2020.01, Varicella zoster virus (VZV) causes a life-threatening infection in immunocompromised hosts. The immune response to VZV of healthy subjects has been rigorously assessed, but little is known about that of immunocompromised individuals. This study aimed to clarify the primary response to VZV infection in immunocompromised children. This prospective study enrolled six immunocompromised children (median age, 33 months; range, 20-62) receiving steroids or immunosuppressants, and 10 immunocompetent children (median age, 32 months; range, 15-81) with varicella. The immunocompromised children were three patients with acute lymphoblastic leukemia, two recipients with liver transplantation and one patient with juvenile idiopathic arthritis. Interferon-γ-producing CD69+ T-cells produced by VZV stimulation (VZV-specific T-cells) were studied during the acute or convalescent phase. To further address the direct effect of immunosuppressants, we analyzed the number of VZV-specific T-cells after stimulating peripheral bl ood mononucl ear cel l s obtai ned from heal thy adul ts wi th l i ve-attenuated VZV wi th or wi thout prednisolone, cyclosporine-A, or tacrolimus. The circulating numbers of lymphocytes in the convalescent stage but not acute stage were lower in immunocompromised children compared with immunocompetent children. In the acute stage, immunocompromised patients showed lower VZV-specific CD8+T-cell counts than immunocompetent subjects. In contrast, in the convalescent phase, immunocompromised patients had lower VZV-specific CD4+T-cell counts than immunocompetent hosts. The in vitro culture of activated lymphocytes with prednisolone or immunosuppressants significantly decreased the proportion of VZV-specific CD4+ T-cells. In conclusion, the decreased numbers of VZV-specific CD8+ T-cells during the acute phase and VZV-specific CD4+ T-cells during the convalescent phase of disease may account for severe varicella in immunocompromised children..|
|13.||Tamaki Ueda, Yuhki Koga, Hiroshi Yoshikawa, Mika Tanabe, Kanako Yamana, Utako Oba, Kentaro Nakashima, Hiroaki Ono, Takuya Ichimura, Shunji Hasegawa, Wakako Kato, Tetsuko Kobayashi, Hideki Nakayama, Yasunari Sakai, Tadamasa Yoshitake, Saiji Ohga, Yoshinao Oda, Shigenobu Suzuki, Koh Hei Sonoda, Shouichi Ohga, Survival and ocular preservation in a long-term cohort of Japanese patients with retinoblastoma, BMC Pediatrics, 10.1186/s12887-020-1923-7, 20, 1, 2020.01, Background: Retinoblastoma is an ocular tumor in infants with cancer predisposition. Treatment of the rare tumor needs to be optimized for ocular preserved survival without second primary malignancy (SPM). Methods: We studied the outcomes of all patients with retinoblastoma at a tertiary center in 1984-2016, when preservation method changed from radiotherapy (1984-2001) to systemic chemotherapy (2002-2016). Results: One-hundred sixteen infants developed unilateral- (n = 77), bilateral- (n = 38), or trilateral-onset (n = 1) tumor. Ten (8.6%) had a positive family history, despite a few studies on RB1 gene. Contralateral disease occurred in one unilateral-onset case. One-hundred eight of 155 eyes (70%) were enucleated. Nine binocular survivors were from 5 bilateral- and 4 unilateral-onset cases. Two survivors received bilateral enucleation. Six deaths occurred; brain involvement (including 3 trilateral diseases) in 4 bilateral-onset, systemic invasion in a unilateral-onset, and SPM (osteosarcoma) in a bilateral-onset case(s). Two others survived SPM of osteosarcoma or lymphoma. The 10-year overall survival (OS: 98.5% vs. 91.3%, p = 0.068) and binocular survivors (13.2% vs. 5.2%, p = 0.154) between bilateral- and unilateral-onsets did not differ statistically. The 10-year OS and cancer (retinoblastoma/SPM)-free survival (CFS) rates of all patients were 94.9 and 88.5%, respectively. The proportion of preserved eyes did not differ between radiotherapy and chemotherapy eras. The CFS rate of bilateral-onset cases in systemic chemotherapy era was higher than that in radiotherapy era (p = 0.042). The CFS rates of bilateral-onset patients with neoadjuvant chemotherapy (upfront systemic therapy for preservation) was higher than those without it (p = 0.030). Conclusions: Systemic chemotherapy and local therapy raised OS and binocular survival rates of bilateral-onset patients similarly to those of unilateral-onset patients. All but one death was associated with a probable germline defect of the RB1 gene. Neoadjuvant stratified chemotherapy may support the long-term binocular life with minimized risk of SPM..|
|14.||Kazuko Kudo, Miho Maeda, Nobuhiro Suzuki, Hirokazu Kanegane, Shouichi Ohga, Eiichi Ishii, Yoko Shioda, Toshihiko Imamura, Shinsaku Imashuku, Yukiko Tsunematsu, Mikiya Endo, Akira Shimada, Yuuki Koga, Yoshiko Hashii, Maiko Noguchi, Masami Inoue, Ken Tabuchi, Akira Morimoto, Nationwide retrospective review of hematopoietic stem cell transplantation in children with refractory Langerhans cell histiocytosis., Int. J. Hematol., 10.1007/s12185-019-02760-5, 111, 1, 137-148, 2020.01, The efficacy of and indications for hematopoietic stem cell transplantation (HSCT) in pediatric Langerhans cell histiocytosis (LCH) remain undetermined. This retrospective study analyzed 30 children with refractory LCH who underwent HSCT in Japan between 1996 and 2014. Eleven patients received a myeloablative conditioning (MAC) regimen, while 19 patients received a reduced-intensity conditioning (RIC) regimen. Among the 26 patients with complete data, 23 patients had risk organ (RO) involvement during clinical course. Disease status at HSCT was no active disease (NAD) (4), active disease-regression (AD-r) (2), active disease-stable (AD-s) (4), and active disease-progressive (AD-p) (16). Seventeen of the 30 patients (57%) were alive with a median follow-up of 433 days (range 9-5307) after HSCT. Death occurred within 3 months after HSCT in eight of 13 patients. RIC and MAC patients were similar in both overall survival (OS) (56.8% vs. 63.6%, respectively, p = 0.789) and failure-free survival (56.8% vs. 54.6%, respectively, p = 0.938). Regarding disease status at HSCT, the six patients with NAD/AD-r experienced better outcomes than the 20 with AD-s/AD-p (5-year OS, 100% vs. 5.|
|15.||Prognostic factors for survival of herpes simplex virus-associated hemophagocytic lymphohistiocytosis..|
|16.||Junko Fujiyoshi, Haruyoshi Yamaza, Soichiro Sonoda, Ratih Yuniartha, Kenji Ihara, Kazuaki Nonaka, Tomoaki Taguchi, Shouichi Ohga, Takayoshi Yamaza, Therapeutic potential of hepatocyte-like-cells converted from stem cells from human exfoliated deciduous teeth in fulminant Wilson’s disease, Scientific reports, 10.1038/s41598-018-38275-y, 9, 1, 2019.12, Wilson’s disease (WD) is an inherited metabolic disease arising from ATPase copper transporting beta gene (ATP7B) mutation. Orthotoropic liver transplantation is the only radical treatment of fulminant WD, although appropriate donors are lacking at the onset of emergency. Given the hepatogenic capacity and tissue-integration/reconstruction ability in the liver of stem cells from human exfoliated deciduous teeth (SHED), SHED have been proposed as a source for curing liver diseases. We hypothesized the therapeutic potential of SHED and SHED-converted hepatocyte-like- cells (SHED-Heps) for fulminant WD. SHED and SHED-Heps were transplanted into WD model Atp7b-mutated Long-Evans Cinnamon (LEC) rats received copper overloading to induce a lethal fulminant liver failure. Due to the superior copper tolerance via ATP7B, SHED-Hep transplantation gave more prolonged life-span of fulminant LEC rats than SHED transplantation. The integrated ATP7B-expressing SHED-Heps showed more therapeutic effects on to restoring the hepatic dysfunction and tissue damages in the recipient liver than the integrated naïve SHED without ATP7B expression. Moreover, SHED-Heps could reduce copper-induced oxidative stress via ATP7B- independent stanniocalcin 1 secretion in the fulminant LEC rats, suggesting a possible role for paracrine effect of the integrated SHED-Heps. Taken together, SHED-Heps offer a potential of functional restoring, bridging, and preventive approaches for treating fulminant WD..|
|17.||De novo p.G696S mutation in COL4A1 causes intracranial calcification and late-onset cerebral hemorrhage: A case report and review of the literature..|
|18.||, Yuki Matsushita, Yasunari Sakai, Michiko Torio, Hirosuke Inoue, Masayuki Ochiai, Kazuaki Yasuoka, Hiroaki Kurata, Junko Fujiyoshi, Masako Ichiyama, Tomoaki Taguchi, Kiyoko Kato, Shouichi Ohga, Association of perinatal factors of epilepsy in very low birth weight infants, using a nationwide database in Japan, Journal of Perinatology, 10.1038/s41372-019-0494-7, 39, 11, 1472-1479, 2019.11, Objective: To determine clinical features of very low birth weight infants (VLBWIs) who had developed epilepsy by age 3 years. Study design: Multicenter cohort study using the Neonatal Research Network of Japan database. We analyzed clinical variables of 8431 VLBWIs who had recorded data of neurological sequelae at age 3 years. Logistic regression identified the association between variables and development of epilepsy. Result: One hundred and forty-three (1.7%) infants developed epilepsy, 683 (8.1%) showed cerebral palsy (CP), and 1114 (13.2%) had psychomotor delay. Epilepsy was associated with history of sepsis [adjusted odds ratio (AOR) 3.23], severe intraventricular hemorrhage (IVH; AOR 5.13), and cystic periventricular leukomalacia (PVL; AOR 12.7). Severe IVH and cystic PVL were also frequently associated with CP and psychomotor delay. Conclusion: Severe IVH and cystic PVL are strongly associated with development of epilepsy, as well as other neurological sequelae, and are potential critical therapeutic targets..|
|19.||Ken ichiro Konishi, Tatsuki Mizuochi, Tadahiro Yanagi, Yoriko Watanabe, Kazuhiro Ohkubo, Shouichi Ohga, Hidehiko Maruyama, Ichiro Takeuchi, Yuji Sekine, Kei Masuda, Nobuyuki Kikuchi, Yuka Yotsumoto, Yasufumi Ohtsuka, Hidenori Tanaka, Takahiro Kudo, Atsuko Noguchi, Kazumasa Fuwa, Sotaro Mushiake, Shinobu Ida, Jun Fujishiro, Yushiro Yamashita, Tomoaki Taguchi, Ken Yamamoto, Clinical Features, Molecular Genetics, and Long-Term Outcome in Congenital Chloride Diarrhea
A Nationwide Study in Japan, Journal of Pediatrics, 10.1016/j.jpeds.2019.07.039, 214, 151-157.e6, 2019.11, Objective: To clarify clinical and genetic features of Japanese children with congenital chloride diarrhea (CCD). Study design: This was a multi-institutional, retrospective survey of 616 pediatric centers in Japan with identified patients with CCD between 2014 and 2018. Mutations involving SLC26A3 were detected by Sanger sequencing. Results: Thirteen patients met all entry criteria including mutations in SLC26A3, and 14 patients satisfied clinical diagnostic criteria. Homozygous or compound heterozygous mutations in SLC26A3, including 6 novel mutations, were identified in 13 of these 14 patients (93%). The most common (detected in 7 of 13) was c.2063-1g>t. Median age at diagnosis was 1 day. Nine of the patients meeting all criteria were diagnosed as neonates (69%). Median follow-up duration was 10 years. When studied, 8 patients had <5 stools daily (62%), and all had fewer than in infancy. Only 1 patient had nephrocalcinosis, and 3 (23%) had mild chronic kidney disease. Neurodevelopment was generally good; only 1 patient required special education. Five patients (38%) received long-term sodium, potassium, and chloride supplementation. Conclusions: Early fetal ultrasound diagnosis and prompt long-term sodium, potassium, and chloride supplementation were common management features. Genetic analysis of SLC26A3 provided definitive diagnosis of CCD. In contrast with previously reported localities, c.2063-1g>t might be a founder mutation in East Asia..
|20.||Takuya Oda, Hazumu Nagata, Yasutaka Nakashima, Etsuro Nanishi, Yui Takada, Manao Nishimura, Eiji Kubo, Ken Hatae, Shouichi Ohga, Clinical Utility of Highly Purified 10% Liquid Intravenous Immunoglobulin in Kawasaki Disease, Journal of Pediatrics, 10.1016/j.jpeds.2019.06.018, 214, 227-230, 2019.11, Compared with a 5% intravenous immunoglobulin, a 10% intravenous immunoglobulin as the first-line treatment of Kawasaki disease significantly reduced the fever duration (10 vs 13 hours, P = .022) among the responders, and the interval to adjunctive therapy for nonresponders (47 vs 49 hours, P = .035). There were no severe adverse events..|
|21.||C. Matsuguma, H. Wakiguchi, Y. Suzuki, S. Okada, T. Furuta, Y. Ohnishi, Y. Azuma, S. Ohga, S. Hasegawa, Dynamics of immunocyte activation during intravenous immunoglobulin treatment in Kawasaki disease, Scandinavian Journal of Rheumatology, 10.1080/03009742.2019.1604992, 48, 6, 491-496, 2019.11, Objectives: Kawasaki disease (KD) is a systemic vasculitis of early childhood. Intravenous immunoglobulin (IVIG) is the standard treatment for KD. However, IVIG is not effective in approximately 15% of children with KD, and the mechanisms for this are unclear. We investigated changes in monocyte and T-cell activation from pre- to post-IVIG in IVIG-effective and IVIG-resistant KD. Method: We analysed peripheral CD14+CD16+ cells and human leucocyte antigen-DR (HLA-DR) expression on CD4+ and CD8+ cells in 46 children with KD who were admitted to Yamaguchi University Hospital between January 2011 and May 2016. We compared the kinetics in the absolute numbers of CD14+CD16+ cells, CD4+HLA-DR+ cells, and CD8+HLA-DR+ cells before and after IVIG treatment between IVIG-effective and IVIG-resistant groups. Results: Among the 46 subjects, 30 had IVIG-effective KD and 16 had IVIG-resistant KD. The absolute number of CD14+CD16+ cells in the IVIG-effective group decreased significantly after IVIG, while that in the IVIG-resistant group showed no change after IVIG. The absolute number of CD4+HLA-DR+ cells increased significantly after IVIG in both groups. The absolute number of CD8+HLA-DR+ cells before IVIG was low and significantly increased after IVIG in the IVIG-resistant group, while that in the IVIG-effective group showed no change after IVIG. Conclusions: Our results suggest that insufficient control of monocyte suppression and T-cell activation, especially in terms of the CD8-related immune system, are associated with IVIG resistance. The restoration of T-cell suppression may be important for KD recovery. These findings provide insight into the mechanism of IVIG resistance..|
|22.||Nozomi Abe, Hiroki Yasudo, Reiji Fukano, Tamaki Nakamura, Seigo Okada, Hiroyuki Wakiguchi, Fumiko Okazaki, Komei Shirabe, Shoichi Toda, Reiko Okamoto, Kazunobu Ouchi, Shouichi Ohga, Shunji Hasegawa, Multi-season analyses of causative pathogens in children hospitalized with asthma exacerbation, Pediatric Allergy and Immunology, 10.1111/pai.13102, 30, 7, 724-731, 2019.11, Background: Respiratory viral and mycoplasma infections are associated with childhood asthma exacerbations. Here, we explored epidemiologic profile of causative pathogens and possible factors for exacerbation in a single center over a three-year period. Methods: Hospitalized asthmatic children with attack aged 6 months-17 years were recruited between 2012 and 2015 (n = 216). Nasopharyngeal mucosa cell samples were collected from the participants and examined by reverse transcription-polymerase chain reaction to detect rhinovirus (RV), respiratory syncytial virus (RSV), enterovirus (EV), parainfluenza virus (PIV), Mycoplasma pneumoniae, and others. Clinical features, laboratory data, asthma exacerbation intensity, and asthma severity were compared among participants. Epidemiologic profile of causative pathogens and possible factors for exacerbation were explored. Results: Viruses and/or Mycoplasma pneumoniae were detected in 75% of the participants. Rhinovirus (48%) was the most commonly detected virus in the participants with single infection, followed by RSV (6%). The median age at admission in the RV group was significantly higher than that in the RSV group. Insufficient asthma control and allergen sensitization were significantly related to RV-associated asthma exacerbation. There was no seasonality of pathogen types associated with asthma exacerbation although a sporadic prevalence of EV-D68 was observehinovirud. Rhinovirus were repeatedly detected in multiple admission cases. Conclusion: Our three-year analysis revealed that patients with RV infection were significantly prone to repeated RV infection in the subsequent exacerbation and good asthma control could prevent RV-associated asthma development and exacerbation. Multiple-year monitoring allowed us to comprehend the profile of virus- and/or mycoplasma-induced asthma exacerbation..|
|23.||Hidetoshi Mezawa, Sayaka Aoki, Shoji F. Nakayama, Hiroshi Nitta, Natsuha Ikeda, Keiko Kato, Satoshi Tamai, Makoto Takekoh, Masafumi Sanefuji, Shouichi Ohga, Masako Oda, Hiroshi Mitsubuchi, Ayako Senju, Koichi Kusuhara, Mari Kuwajima, Tatsuya Koeda, Yukihiro Ohya, Keiji Hashimoto, Psychometric profile of the Ages and Stages Questionnaires, Japanese translation, Pediatrics International, 10.1111/ped.13990, 61, 11, 1086-1095, 2019.11, Background: This study assessed the psychometric profile of 10 questionnaires (every 6 months, from 6 to 60 months) from the Japanese translation of the Ages and Stages Questionnaires, third edition (J-ASQ-3). Methods: Data from 439 children in a birth cohort were used to identify the J-ASQ-3 score distribution, establish cut-off scores, and calculate the instrument's internal consistency. Data were also collected from 491 outpatients to examine J-ASQ-3 test–retest reliability and concurrent validity, which was examined using the Kyoto Scale of Psychological Development (KSPD) and the Japanese version of the Denver Developmental Screening Test II (J-Denver II). Both the original and the alternative screening criteria of the ASQ-3 were used (failure in at least one and at least two domains, respectively). Results: Cronbach's alpha for each J-ASQ-3 subscale on each questionnaire ranged from 0.45 to 0.89. Test–retest reliability was >0.75 for the subscales on almost all questionnaires. Concurrent validity was also adequate. In comparison with the screening results of the KSPD, the overall sensitivity and specificity were 96.0% and 48.8%, respectively, when the ASQ-3 original criterion was used, and 92.1% and 74.9%, respectively, when the alternative criterion was used. In comparison with the screening results of the J-Denver II, the overall sensitivity and specificity were 75.6% and 74.7%, respectively, when the ASQ-3 original criterion was used, and 56.3% and 93.0%, respectively, when the alternative criterion was used. Conclusions: This study quantified the psychometric profiles of the Japanese translations of 10 ASQ-3 questionnaires. We demonstrated the validity of the J-ASQ-3 and determined new cut-off scores. Further studies with larger samples from a greater range of locations are required to clarify the suitability of this tool for all Japanese children..|
|24.||Kazufumi Kunimura, Daiji Sakata, Xin Tun, Takehito Uruno, Miho Ushijima, Tomoya Katakai, Akira Shiraishi, Ryosuke Aihara, Yasuhisa Kamikaseda, Keisuke Matsubara, Hirokazu Kanegane, Shinichiro Sawa, Gérard Eberl, Shouichi Ohga, Yasunobu Yoshikai, Yoshinori Fukui, S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches, Cell Reports, 10.1016/j.celrep.2019.10.091, 29, 9, 2823-2834.e7, 2019.11, Intestinal microfold cells (M cells) in Peyer's patches are a special subset of epithelial cells that initiate mucosal immune responses through uptake of luminal antigens. Although the cytokine receptor activator of nuclear factor-κB ligand (RANKL) expressed on mesenchymal cells triggers differentiation into M cells, other environmental cues remain unknown. Here, we show that the metastasis-promoting protein S100A4 is required for development of mature M cells. S100A4-producing cells are a heterogenous cell population including lysozyme-expressing dendritic cells and group 3 innate lymphoid cells. We found that in the absence of DOCK8, a Cdc42 activator critical for interstitial leukocyte migration, S100A4-producing cells are reduced in the subepithelial dome, resulting in a maturation defect of M cells. While S100A4 promotes differentiation into mature M cells in organoid culture, genetic inactivation of S100a4 prevents the development of mature M cells in mice. Thus, S100A4 is a key environmental cue that regulates M cell differentiation in collaboration with RANKL..|
|25.||Yuki Matsushita, Yasunari Sakai, Michiko Torio, Hirosuke Inoue, Masayuki Ochiai, Kazuaki Yasuoka, Hiroaki Kurata, Junko Fujiyoshi, Masako Ichiyama, Tomoaki Taguchi, Kiyoko Kato, Shouichi Ohga, Association of perinatal factors of epilepsy in very low birth weight infants, using a nationwide database in Japan., Journal of perinatology : official journal of the California Perinatal Association, 10.1038/s41372-019-0494-7, 39, 11, 1472-1479, 2019.11, OBJECTIVE: To determine clinical features of very low birth weight infants (VLBWIs) who had developed epilepsy by age 3 years. STUDY DESIGN: Multicenter cohort study using the Neonatal Research Network of Japan database. We analyzed clinical variables of 8431 VLBWIs who had recorded data of neurological sequelae at age 3 years. Logistic regression identified the association between variables and development of epilepsy. RESULT: One hundred and forty-three (1.7%) infants developed epilepsy, 683 (8.1%) showed cerebral palsy (CP), and 1114 (13.2%) had psychomotor delay. Epilepsy was associated with history of sepsis [adjusted odds ratio (AOR) 3.23], severe intraventricular hemorrhage (IVH; AOR 5.13), and cystic periventricular leukomalacia (PVL; AOR 12.7). Severe IVH and cystic PVL were also frequently associated with CP and psychomotor delay. CONCLUSION: Severe IVH and cystic PVL are strongly associated with development of epilepsy, as well as other neurological sequelae, and are potential critical therapeutic targets..|
|26.||Matsuguma C, Wakiguchi H, Suzuki Y, Okada S, Furuta T, Ohnishi Y, Azuma Y, Ohga S, Hasegawa S, Dynamics of immunocyte activation during intravenous immunoglobulin treatment in Kawasaki disease., Scandinavian journal of rheumatology, 10.1080/03009742.2019.1604992, 48, 6, 491-496, 2019.11.|
|27.||Yasutaka Nakashima, Yasunari Sakai, Yumi Mizuno, Kenji Furuno, Keiichi Hirono, Shinichi Takatsuki, Hiroyuki Suzuki, Yoshihiro Onouchi, Tohru Kobayashi, Kazuhiro Tanabe, Kenji Hamase, Tomofumi Miyamoto, Ryohei Aoyagi, Makoto Arita, Kenichiro Yamamura, Tamami Tanaka, Hisanori Nishio, Hidetoshi Takada, Shouichi Ohga, Toshiro Hara, Lipidomics links oxidized phosphatidylcholines and coronary arteritis in Kawasaki disease., Cardiovascular research, 10.1093/cvr/cvz305, 2019.11, AIMS: Coronary arteritis is a life-threatening complication that may arise in the acute stage of Kawasaki disease (KD), the leading cause of systemic vasculitis in childhood. Various microorganisms and molecular pathogens have been reported to cause KD. However, little is known about the key molecules that contribute to the development of coronary arteritis in KD. METHODS AND RESULTS: To identify causative molecules for coronary arteritis in KD, we prospectively recruited 105 patients with KD and 65 disease controls in 4 different parts of Japan from 2015 to 2018. During this period, we conducted lipidomics analyses of their sera using liquid chromatography (LC)-mass spectrometry (MS). The comprehensive LC-MS system detected a total of 27,776 molecules harboring the unique retention time and m/z values. In the first cohort of 57 KD patients, we found that a fraction of these molecules showed enrichment patterns that varied with the sampling region and season. Among them, 28 molecules were recurrently identified in KD patients, but not in controls. The second and third cohorts of 48 more patients with KD revealed that these molecules were correlated with inflammatory markers (leukocyte counts and C-reactive proteins) in the acute stage. Notably, two of these molecules (m/z values: 822.55 and 834.59) were significantly associated with the development of coronary arteritis in the acute stage of KD. Their fragmentation patterns in the tandem MS/MS analysis were consistent with those of oxidized phosphatidylcholines. Further LC-MS/MS analysis supported the concept that reactive oxygen species caused the non-selective oxidization of phosphatidylcholines in KD patients. In addition, the concentrations of LOX-1 ligand containing apolipoprotein B in the plasma of KD patients were significantly higher than in controls. CONCLUSION: These data suggest that inflammatory signals activated by oxidized phospholipids are involved in the pathogenesis of coronary arteritis in KD. Because the present study recruited only Japanese patients, further examinations are required to determine whether oxidized phosphatidylcholines might be useful biomarkers for the development of coronary arteritis in broad populations of KD..|
|28.||Abe N, Yasudo H, Fukano R, Nakamura T, Okada S, Wakiguchi H, Okazaki F, Shirabe K, Toda S, Okamoto R, Ouchi K, Ohga S, Hasegawa S, Multi-season analyses of causative pathogens in children hospitalized with asthma exacerbation., Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology, 10.1111/pai.13102, 30, 7, 724-731, 2019.11.|
|29.||S100A4 Protein Is Essential for the Development of Mature Microfold Cells in Peyer's Patches..|
|30.||Yuji Ohnishi, Hiroki Yasudo, Yasuo Suzuki, Takashi Furuta, Chie Matsuguma, Yoshihiro Azuma, Akiko Miyake, Seigo Okada, Kiyoshi Ichihara, Shouichi Ohga, Shunji Hasegawa, Circulating endothelial glycocalyx components as a predictive marker of coronary artery lesions in Kawasaki disease, International Journal of Cardiology, 10.1016/j.ijcard.2019.05.045, 292, 236-240, 2019.10, Background: Kawasaki disease (KD) is acute and self-limited vasculitis caused by unknown origin, and the critical complication in KD patients is coronary artery lesions (CALs). The endothelial glycocalyx is a network of membranes luminally covering the endothelium. This study aimed to evaluate the clinical utility of serum glycocalyx components as biomarkers of predicting the onset CALs in KD. Methods: Seventy subjects with complete type KD, 18 subjects as febrile control (FC), and 15 subjects as afebrile controls (AC) were enrolled. Medical, demographic, echocardiography, and laboratory data from the medical records were retrospectively analyzed. Serum syndecan-1 and hyaluronan levels prior to intravenous immunoglobulin (IVIG) therapy were measured at the acute phase, immediately after IVIG, the subacute phase, and the time of discharge at the convalescent phase. Results: Serum syndecan-1 and hyaluronan levels were higher in the KD group than in the AC and FC groups at all three phases. Further, these levels were compared between KD patients with and without the development of CALs. Serum syndecan-1 and hyaluronan levels at the acute phase were significantly elevated in KD patients with the CALs than in those without CALs. Serum hyaluronan, not syndecan-1, was determined as the most contributory parameter to predict CALs by a multiple logistic analysis. Conclusions: Circulating syndecan-1 and hyaluronan can be useful biomarkers to predict the development of CALs in KD..|
|31.||Circulating endothelial glycocalyx components as a predictive marker of coronary artery lesions in Kawasaki disease..|
|32.||Hiroki Hamano, Takeshi Matsushige, Hirofumi Inoue, Madoka Hoshide, Hikaru Kobayashi, Fumitaka Kohno, Momoko Oka, Takashi Ichiyama, Shouichi Ohga, Kazunobu Ouchi, Shunji Hasegawa, A case of acute encephalophathy with residual neurological sequelae induced by immunoglobulin A vasculitis, Journal of Clinical Neuroscience, 10.1016/j.jocn.2019.05.061, 67, 270-271, 2019.09, Immunoglobulin A vasculitis (IgAV) occasionally induces central nervous system (CNS) involvement, which is usually transient with no sequelae except for hemorrhagic stroke. It is thought to be useful to measure serum and cerebrospinal fluid (CSF) cytokine levels for better understanding the pathological condition in encephalopathy, but there have been no reports in acute encephalopathy with IgAV. We describe an 8-year-old boy with IgAV who had neurological sequelae after complication of acute encephalopathy, focusing on the cytokine profiles and unique biphasic findings of magnetic resonance imaging. He presented with status epilepticus and mildly intensified area in the occipital lobe on the fluid-attenuated inversion recovery view. Arterial spin labeling (ASL) revealed the reduction of cerebral blood flow in the left hemisphere. On day 5 of illness, these abnormal findings disappeared, but delayed hyperintensity lesions on diffusion-weighted images newly emerged. Furthermore, CSF interleukin (IL)-6 levels markedly increased without elevated levels of IL-10 during the acute phase of disease. He suffered from long-lasting hemiparesis and intellectual impairment. In conclusion, acute encephalopathy with IgAV could cause neurological sequelae by prolonged seizure, and elevated IL-6 in CSF and laterality of cerebral blood flow in ASL might be useful to predict the prognosis of CNS dysfunction of IgAV..|
|33.||Kazuaki Yasuoka, Hirosuke Inoue, N. Egami, Masayuki Ochiai, Koichi Tanaka, Toru Sawano, Hiroaki Kurata, Masako Ichiyama, J. Fujiyoshi, Yuki Matsushita, Yasunari Sakai, Shouichi Ohga, Late-Onset Circulatory Collapse and Risk of Cerebral Palsy in Extremely Preterm Infants, Journal of Pediatrics, 10.1016/j.jpeds.2019.05.033, 212, 117-123.e4, 2019.09, Objective: To investigate whether the development of postnatal, late-onset refractory hypotension, referred to as late-onset circulatory collapse, was associated with an increased risk of developing cerebral palsy (CP) at 3 years of age in extremely preterm infants. Methods: In this historical cohort study, infants who were born at 22-27 weeks of gestation from 2008 to 2012 in the Neonatal Research Network of Japan were eligible. The study sample consisted of 3474 infants (45.6% of 7613 potentially eligible infants) who were evaluated at 36-42 months of age. Late-onset circulatory collapse was defined as a clinical diagnosis of late-onset circulatory collapse requiring treatment with corticosteroids. We compared the neurodevelopmental outcomes between infants with and without late-onset circulatory collapse. Results: Late-onset circulatory collapse was diagnosed in 666 of the infants studied. Infants with late-onset circulatory collapse had a higher incidence of CP than those without late-onset circulatory collapse (18.0% vs 9.8%; P < .01). In multivariable logistic analysis, late-onset circulatory collapse was independently associated with CP (aOR, 1.52; 95% CI, 1.13-2.04) and developmental quotient score of <50 (OR, 1.83; 95% CI, 1.23-2.72). Conclusions: Late-onset circulatory collapse may be a relatively common event occurring in extremely preterm infants and an independent risk factor for CP at 3 years of age..|
|34.||Sayo Mori, Hazumu Nagata, Ichiro Sakamoto, Keiji Oi, Shouichi Ohga, Successful stent implantation for acute take-off left coronary artery stenosis, Pediatrics International, 10.1111/ped.13942, 61, 9, 933-935, 2019.09.|
|35.||Kazuaki Yasuoka, Hirosuke Inoue, Naoki Egami, Masayuki Ochiai, Koichi Tanaka, Toru Sawano, Hiroaki Kurata, Masako Ichiyama, Junko Fujiyoshi, Yuki Matsushita, Yasunari Sakai, Shouichi Ohga, Late-Onset Circulatory Collapse and Risk of Cerebral Palsy in Extremely Preterm Infants., The Journal of pediatrics, 10.1016/j.jpeds.2019.05.033, 212, 117-123, 2019.09, OBJECTIVE: To investigate whether the development of postnatal, late-onset refractory hypotension, referred to as late-onset circulatory collapse, was associated with an increased risk of developing cerebral palsy (CP) at 3 years of age in extremely preterm infants. METHODS: In this historical cohort study, infants who were born at 22-27 weeks of gestation from 2008 to 2012 in the Neonatal Research Network of Japan were eligible. The study sample consisted of 3474 infants (45.6% of 7613 potentially eligible infants) who were evaluated at 36-42 months of age. Late-onset circulatory collapse was defined as a clinical diagnosis of late-onset circulatory collapse requiring treatment with corticosteroids. We compared the neurodevelopmental outcomes between infants with and without late-onset circulatory collapse. RESULTS: Late-onset circulatory collapse was diagnosed in 666 of the infants studied. Infants with late-onset circulatory collapse had a higher incidence of CP than those without late-onset circulatory collapse (18.0% vs 9.8%; P < .01). In multivariable logistic analysis, late-onset circulatory collapse was independently associated with CP (aOR, 1.52; 95% CI, 1.13-2.04) and developmental quotient score of <50 (OR, 1.83; 95% CI, 1.23-2.72). CONCLUSIONS: Late-onset circulatory collapse may be a relatively common event occurring in extremely preterm infants and an independent risk factor for CP at 3 years of age..|
|36.||Tadamune Kinjo, Hirosuke Inoue, Takeshi Kusuda, J. Fujiyoshi, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Y. Koga, Toshiro Hara, Shouichi Ohga, Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis, Pediatrics and Neonatology, 10.1016/j.pedneo.2018.09.005, 60, 4, 382-388, 2019.08, Background: Transient abnormal myelopoiesis (TAM) is a neonatal preleukemic syndrome that occurs exclusively in neonates with Down syndrome (DS). Most affected infants spontaneously resolve, although some patients culminate in hepatic failure despite the hematological remission. It is impossible to determine the patients who are at high risk of progressive liver disease and leukemic transformation. The objective is to search for biomarkers predicting the development of hepatic failure in DS infants with TAM. Methods: Among 60 newborn infants with DS consecutively admitted to our institutions from 2003 to 2016, 41 infants with or without TAM were enrolled for the study. Twenty-two TAM-patients were classified into “progression group” (n = 7) that required any therapy and “spontaneous resolution group” (n = 15). Serum concentrations of chemokines (CXCL8, CXCL9, CXCL10, CCL2 and CCL5) and transforming growth factor (TGF)-β1 were measured at diagnosis of TAM for assessing the outcome of progressive disease. Results: Three patients developed leukemia during the study period (median, 1147 days; range, 33–3753). Three died of hepatic failure. All patients in the progression group were preterm birth <37 weeks of gestational age and were earlier than those in the spontaneous resolution group (median, 34.7 vs. 37.0 weeks, p < 0.01). The leukocyte counts and CXCL8 and CCL2 levels at diagnosis in the progression group were higher than those in the spontaneous resolution group (leukocyte: median, 81.60 vs. 27.30 × 109/L, p = 0.01; CXCL8: 173.8 vs. 34.3 pg/ml, p < 0.01; CCL2: 790.3 vs. 209.8 pg/mL, p < 0.01). Multivariate analyses indicated that an increased CCL2 value was independently associated with the progression and CXCL8 with the death of liver failure, respectively (CCL2: standardized coefficient [sc], 0.43, p < 0.01; CXCL8: sc = −0.46, p = 0.02). Conclusion: High levels of circulating CXCL8 and CCL2 at diagnosis of TAM may predict progressive hepatic failure in DS infants..|
|37.||Momoko Sasazuki, Yasunari Sakai, Ryutaro Kira, Naoko Toda, Yuko Ichimiya, Satoshi Akamine, Michiko Torio, Yoshito Ishizaki, Masafumi Sanefuji, Miho Narama, Koichiro Itai, Toshiro Hara, Hidetoshi Takada, Yoshiyuki Kizawa, Shouichi Ohga, Decision-making dilemmas of paediatricians
A qualitative study in Japan, BMJ open, 10.1136/bmjopen-2018-026579, 9, 8, 2019.08, Objective To delineate the critical decision-making processes that paediatricians apply when treating children with life-threatening conditions and the psychosocial experience of paediatricians involved in such care. Design We conducted semistructured, individual face-to-face interviews for each participant from 2014 to 2015. The content of each interview was subjected to a comprehensive qualitative analysis. The categories of dilemma were extracted from a second-round content analysis. Participants Participants were board-certified paediatricians with sufficient experience in making decisions in relation to children with severe illnesses or disabilities. We repeated purposive sampling and analyses until we reached saturation of the category data. Results We performed interviews with 15 paediatricians. They each reported both unique and overlapping categories of dilemmas that they encountered when making critical decisions. The dilemmas included five types of causal elements: (1) paediatricians' convictions; (2) the quest for the best interests of patients; (3) the quest for medically appropriate plans; (4) confronting parents and families and (5) socioenvironmental issues. Dilemmas occurred and developed as conflicting interactions among these five elements. We further categorised these five elements into three principal domains: the decision-maker (decider); consensus making among families, colleagues and society (process) and the consequential output of the decision (consequence). Conclusions This is the first qualitative study to demonstrate the framework of paediatricians' decision-making processes and the complex structures of dilemmas they face. Our data indicate the necessity of establishing and implementing an effective support system for paediatricians, such as structured professional education and arguments for creating social consensus that assist them to reach the best plan for the management of severely ill children..
|38.||Naoki Ohta, Hiroki Yasudo, Makoto Mizutani, Takeshi Matsushige, Reiji Fukano, Setsuaki Kittaka, Kenji Maehara, Kiyoshi Ichihara, Shouichi Ohga, Shunji Hasegawa, Serum soluble ST2 as a marker of renal scar in pediatric upper urinary tract infection, Cytokine, 10.1016/j.cyto.2019.05.006, 120, 258-263, 2019.08, Background and objectives: Upper urinary tract infection is the most common serious bacterial infection in childhood. Patients with upper urinary tract infection have a risk for renal scarring with subsequent complications including hypertension, proteinuria, and progressive renal failure. However, the predictive biomarkers of renal scarring in children with upper urinary tract infection are still unknown. In this study, we evaluated whether soluble ST2 levels can be biomarkers of subsequent renal scarring in patients with upper urinary tract infection. Design, setting, participants, and measurements: We retrospectively studied pediatric patients with upper urinary tract infection at a tertiary center. Twenty-eight children had an upper urinary tract infection with (n = 14) and without (n = 14) renal scarring and underwent 99mtechnetium dimercaptosuccinic acid imaging. In addition, 13 control subjects were enrolled. The clinical data and serum cytokine levels, including soluble ST2 levels, were compared between those with and without renal scars. Results: Serum soluble ST2 levels were significantly higher in the scar group than in the non-scar group, whereas there was no difference in the levels of serum interferon-γ, interleukin-6, interleukin-10, soluble tumor necrosis factor receptor 1, and transforming growth factor-β between the scar and non-scar groups. The area under the curve for differentiating between the non-scar and scar groups on the basis of measurements of serum soluble ST2 was 0.79, with a sensitivity and specificity of 92.9% and 64.3%, respectively. Conclusion: These results suggest that serum soluble ST2 levels on admission could be a useful biomarker of subsequent renal scarring in pediatric patients with upper urinary tract infection..|
|39.||Soichi Mizuguchi, Yoshitomo Motomura, Jun Maki, Rieko Baba, Yuko Ichimiya, Kentaro Tokuda, Noriyuki Kaku, Hidetoshi Takada, Yoshihiko Maehara, Shouichi Ohga, Tracheal Size and Morphology on the Reconstructed CT Imaging, Pediatric Critical Care Medicine, 10.1097/PCC.0000000000001996, 20, 8, E366-E371, 2019.08, Objectives: To characterize the real size and morphology of tracheas in childhood for the optimal selection of endotracheal tube. Design: A retrospective cohort study of pediatric patients who received CT scan of the cervical spine from July 2011 to March 2018. Cross-sectional CT images vertical to trachea were reconstructed and the accurate tracheal diameters were measured. The validity of the traditional age-based formula for predicting the endotracheal tube size was assessed for the best fit to trachea. Setting: Tertiary Emergency and Critical Care Center of Kyushu University Hospital. Patients: Children, who are 1 month to 15 years old, received CT scan of the cervical spine. Interventions: None. Measurements and Main Results: We enrolled 86 children with median age of 53 months. The cross-sectional shape of pediatric trachea was circular at the cricoid level and elliptical at the infraglottic level. The narrowest part of pediatric trachea was the transverse diameter at the infraglottic level at any age. Significant positive correlation between age and the narrowest diameter was observed. When compared the transverse diameter at the infraglottic level with the outer diameter of endotracheal tubes, uncuffed endotracheal tubes selection based on the traditional age-based formula ran a significant risk of oversized endotracheal intubation until 10 years old compared with cuffed endotracheal tubes selection (60.0% vs 23.8%; p < 0.05). Conclusions: These findings indicate the safety and efficacy of cuffed endotracheal tubes in infants and children and the reconsideration for the airway management in pediatric anesthesia and intensive care..|
|40.||Masayuki Ochiai, Hazumu Nagata, Koichi Tanaka, Kenji Ihara, Shouichi Ohga, Critical association of Pallister-Hall syndrome and congenital heart disease., Pediatrics international : official journal of the Japan Pediatric Society, 10.1111/ped.13945, 61, 8, 827-828, 2019.08.|
|41.||Momoko Sasazuki, Yasunari Sakai, Ryutaro Kira, Naoko Toda, Yuko Ichimiya, Satoshi Akamine, Michiko Torio, Yoshito Ishizaki, Masafumi Sanefuji, Miho Narama, Koichiro Itai, Toshiro Hara, Hidetoshi Takada, Yoshiyuki Kizawa, Shouichi Ohga, Decision-making dilemmas of paediatricians: a qualitative study in Japan., BMJ open, 10.1136/bmjopen-2018-026579, 9, 8, e026579, 2019.08, OBJECTIVE: To delineate the critical decision-making processes that paediatricians apply when treating children with life-threatening conditions and the psychosocial experience of paediatricians involved in such care. DESIGN: We conducted semistructured, individual face-to-face interviews for each participant from 2014 to 2015. The content of each interview was subjected to a comprehensive qualitative analysis. The categories of dilemma were extracted from a second-round content analysis. PARTICIPANTS: Participants were board-certified paediatricians with sufficient experience in making decisions in relation to children with severe illnesses or disabilities. We repeated purposive sampling and analyses until we reached saturation of the category data. RESULTS: We performed interviews with 15 paediatricians. They each reported both unique and overlapping categories of dilemmas that they encountered when making critical decisions. The dilemmas included five types of causal elements: (1) paediatricians' convictions; (2) the quest for the best interests of patients; (3) the quest for medically appropriate plans; (4) confronting parents and families and (5) socioenvironmental issues. Dilemmas occurred and developed as conflicting interactions among these five elements. We further categorised these five elements into three principal domains: the decision-maker (decider); consensus making among families, colleagues and society (process) and the consequential output of the decision (consequence). CONCLUSIONS: This is the first qualitative study to demonstrate the framework of paediatricians' decision-making processes and the complex structures of dilemmas they face. Our data indicate the necessity of establishing and implementing an effective support system for paediatricians, such as structured professional education and arguments for creating social consensus that assist them to reach the best plan for the management of severely ill children..|
|42.||Hiroshi Kitazawa, Kiwako Yamamoto-Hanada, Mayako Saito-Abe, Tadayuki Ayabe, Hidetoshi Mezawa, Kazue Ishitsuka, Mizuho Konishi, Shoji F. Nakayama, Takehiro Michikawa, Ayako Senju, Mayumi Tsuji, Koichi Kusuhara, Masafumi Sanefuji, Shouichi Ohga, Masako Oda, Hiroshi Mitsubuchi, Takahiko Katoh, Akihiko Ikegami, Natan Mise, Kenji Matsumoto, Hirohisa Saito, Yukihiro Ohya, Egg antigen was more abundant than mite antigen in children's bedding
Findings of the pilot study of the Japan Environment and Children's Study (JECS), Allergology International, 10.1016/j.alit.2019.02.005, 68, 3, 391-393, 2019.07.
|43.||Kenichiro Yamamura, Ichiro Sakamoto, Eiji Morihana, Yuichiro Hirata, Hazumu Nagata, Yuzo Yamasaki, Yukihiko Okumura, Kenichi Kohashi, Kazuhiro Koto, Hiroyuki Tsutsui, Shouichi Ohga, Elevated non-invasive liver fibrosis markers and risk of liver carcinoma in adult patients after repair of tetralogy of Fallot, International Journal of Cardiology, 10.1016/j.ijcard.2019.04.032, 287, 121-126, 2019.07, Background: Congestive hepatopathy and hepatocellular carcinoma is a serious complication after Fontan procedure. Liver fibrosis due to hepatic congestion could occur also in adult patients after repair of tetralogy of Fallot (rTOF). However, the incidence and severity remain unclear. Methods: A total of 111 patients with adult congenital heart disease between 2009 and 2016 were enrolled. Liver fibrosis markers and hemodynamic parameters assessed by cardiac magnetic resonance imaging and catheterization were analyzed in 50 rTOF patients having significant pulmonary regurgitation and/or stenosis, 50 Fontan patients and 11 controls. Results: Liver fibrosis markers in patients with rTOF were significantly higher than controls, and tended to be lower than Fontan patients (median, hyaluronic acid: 25.8 vs. 15.9 vs. 40.8, type IV collagen: 129 vs. 113 vs. 166, ng/mL, p < 0.05, respectively). Patients with rTOF showed abnormal hyaluronic acid levels more frequently than controls, and less frequently than Fontan patients (22% vs. 0% vs. 38%, respectively, p < 0.05). Multivariate analyses indicated a positive association of right atrial pressure with type IV-collagen or hyaluronic acid levels (each, p < 0.001, p = 0.003). Abdominal ultrasonography revealed hepatic congestion in 50% of rTOF patients tested. Liver biopsy of the two rTOF patients with highest hyaluronic acid levels showed pathological evidence of moderate and severe (F2 and F3)liver fibrosis and one had combined hepatocellular and cholangiocarcinoma. Conclusions: We first demonstrated elevated liver fibrosis markers in adult patients with rTOF. These levels may help to predict the progressive liver disease as well as consider the timing of pulmonary valve replacement..|
|44.||Wakako Kato, Miki Nishio, Yoko To, Hideru Togashi, Tak Wah Mak, Hidetoshi Takada, Shouichi Ohga, Tomohiko Maehama, Akira Suzuki, MOB1 regulates thymocyte egress and T-cell survival in mice in a YAP1-independent manner, Genes to Cells, 10.1111/gtc.12704, 24, 7, 485-495, 2019.07, Mammalian STE20-like protein kinase 1/2 (MST1/2) and nuclear Dbf2-related kinase 1/2 (NDR1/2) are core components of Hippo signaling that are also known to be important regulators of lymphocyte trafficking. However, little is understood about the roles of other Hippo pathway molecules in these cells. Here, we present the first analysis of the function of Mps one binder kinase activator-1 (MOB1) in T lymphocytes in vivo. T-cell-specific double knockout (DKO) of MOB1A/B in mice [tMob1 DKO mice] reduces the number of naïve T cells in both the circulation and secondary lymphoid organs, but leads to an accumulation of CD4+CD8− and CD4−CD8+ single-positive (SP) cells in the thymus. In vitro, naïve MOB1A/B-deficient T cells show increased apoptosis and display impaired trafficking capacity in response to the chemokine CCL19. These defects are linked to suppression of the activation of MST and NDR kinases, but are independent of the downstream transcriptional co-activator Yes-associated protein 1 (YAP1). Thus, MOB1 proteins play an important role in thymic egress and T-cell survival that is mediated by a pathway other than conventional Hippo-YAP1 signaling..|
|45.||T. Nakano, R. Yasumatsu, R. Kogo, K. Hashimoto, K. Asai, S. Ohga, H. Yamamoto, T. Nakashima, T. Nakagawa, Parotid gland carcinoma
32 years' experience from a single institute, Journal of Laryngology and Otology, 10.1017/S0022215119001130, 133, 7, 604-609, 2019.07, Background Parotid gland carcinoma is a rare and complicated histopathological classification. Therefore, assembling a sufficient number of cases with long-term outcomes in a single institute can present a challenge.Method The medical records of 108 parotid gland carcinoma patients who were treated at Kyushu University Hospital, Fukuoka, Japan, between 1983 and 2014 were reviewed. The survival outcomes were analysed according to clinicopathological findings.Results Forty-six patients had low clinical stage tumours (I-II), and 62 patients had high clinical stage tumours (III-IV). Fifty-two, 10 and 46 patients had low-, intermediate-and high-grade tumours, respectively. Twenty-seven of 65 cases had positive surgical margins. In high clinical stage and intermediate-to high-grade tumours, adjuvant radiation therapy was correlated with local recurrence-free survival (p = 0.0244). Intermediate-to high-grade tumours and positive surgical margins were significantly associated with disease-specific survival in multivariate analysis (p = 0.0002 and p = 0.0058).Conclusion The results of this study show that adjuvant radiation therapy is useful for improved local control in patients with high clinical stage and intermediate-to high-grade tumours..
|46.||Kato W, Nishio M, To Y, Togashi H, Mak TW, Takada H, Ohga S, Maehama T, Suzuki A, MOB1 regulates thymocyte egress and T-cell survival in mice in a YAP1-independent manner., Genes to cells : devoted to molecular & cellular mechanisms, 10.1111/gtc.12704, 24, 7, 485-495, 2019.07.|
|47.||Etsuro Nanishi, Takayuki Hoshina, Masafumi Sanefuji, Ryo Kadoya, Katsuhiko Kitazawa, Yukie Arahata, Tetsuya Sato, Yoshimichi Hirayama, Katsuki Hirai, Masaaki Yanai, Kaori Nikaido, Akihiko Maeda, Hiroyuki Torisu, Kenji Okada, Yasunari Sakai, Shouichi Ohga, A Nationwide Survey of Pediatric-onset Japanese Encephalitis in Japan, Clinical Infectious Diseases, 10.1093/cid/ciy816, 68, 12, 2099-2104, 2019.06, Background: Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children. Methods: A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles. Results: Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005-15 than that during 1995-2004 (4.3 × 10-3 vs 1.1 × 10-3 per 100000, respectively; P =. 04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis. Conclusions: Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area..|
|48.||Yuri Sonoda, Kenichiro Yamamura, Kanako Ishii, Kazuhiro Ohkubo, Kenji Ihara, Yasunari Sakai, Shouichi Ohga, A child with prostaglandin I2-associated thyrotoxicosis
Case report, JCRPE Journal of Clinical Research in Pediatric Endocrinology, 10.4274/jcrpe.galenos.2018.2018.0169, 11, 2, 207-210, 2019.06, Prostaglandin I2 (PGI2) causes hyperthyroidism, a critical complication in patients with pulmonary arterial hypertension (PAH). However, it remains unknown whether PGI2 may have unfavorable effects on thyroid function in children with congenital portosystemic venous shunt syndrome (CPSVS). We present a boy with CPSVS who developed PAH at seven years of age. During ongoing PGI2 therapy, he experienced thyrotoxicosis at 17 years of age. The literature review showed that the reported 12 patients with PAH (median 11 years of age) developed hyperthyroidism during between one and 11 years of PGI2 treatment. Only one patient survived the acute PAH crisis due to hyperthyroidism. These data provide evidence that prophylactic intervention for hyperthyroidism is indicated for children with CPSVS during PGI2 treatment..
|49.||Kenichi Ogiwara, Keiji Nogami, Kuniyoshi Mizumachi, Takashi Nakagawa, Nozomi Noda, Shouichi Ohga, Midori Shima, Hemostatic assessment of combined anticoagulant therapy using warfarin and prothrombin complex concentrates in a case of severe protein C deficiency, International journal of hematology, 10.1007/s12185-019-02645-7, 109, 6, 650-656, 2019.06, Patients with severe congenital protein (P)C deficiency require long-term anticoagulant management. Recombinant PC concentrates for prophylactic use are not available in Japan; prothrombin complex concentrates (PCC), containing factors (F)II, VII, IX, X, and PC (PPSB-HT®), have been used ‘off-label’ in a few patients. We investigated the combined use of prophylactic PCC and Warfarin (VKA; PT-INR 2.0–2.5) in a severely PC-deficient patient in whom VKA alone did not prevent recurrent purpura. Plasma VKA-dependent factor levels and global PC function (Thrombopath®) were assessed. Plasma activity levels of FII/FVII/FIX/FX post-infusion of PCC (6.3 unit/kg) increased 35/27/27/35 (initial level) to 59/60/38/83 IU/dl, respectively. FVII:C and FIX:C rapidly returned to baseline levels 12–24 h post-infusion, but FII:C and FX:C returned more slowly. PC antigen (< 5%) increased to ~ 15%, followed by return to baseline levels 24 h post-infusion. Global PC function was very low (%PiCi 24%), but improved post-PCC infusion. This potential was slightly detectable even at an undetectable PC level. At day 3, high levels of d-dimer and FDP were observed without thrombotic event, but these improved post-infusion. Although PCC restored VKA-dependent coagulation factors, PC contained in PCC significantly improved global anticoagulation, and was clinically beneficial in this severely deficient patient..|
|50.||Shinya Iwasawa, Kumiko Yanagi, Atsuo Kikuchi, Yasuko Kobayashi, Kazuhiro Haginoya, Hiroshi Matsumoto, Kenji Kurosawa, Masayuki Ochiai, Yasunari Sakai, Atsushi Fujita, Noriko Miyake, Tetsuya Niihori, Matsuyuki Shirota, Ryo Funayama, Shigeaki Nonoyama, Shouichi Ohga, Hiroshi Kawame, Keiko Nakayama, Yoko Aoki, Naomichi Matsumoto, Tadashi Kaname, Yoichi Matsubara, Wataru Shoji, Shigeo Kure, Recurrent de novo MAPK8IP3 variants cause neurological phenotypes, Annals of Neurology, 10.1002/ana.25481, 85, 6, 927-933, 2019.06, c-Jun-amino-terminal kinase-interacting protein 3 (JIP3), encoded by MAPK8IP3, is an adaptor protein of the kinesin-1 complex and essential for axonal transport in neurons. However, an association between MAPK8IP3 variants and human disease has not been established. We identified 5 individuals from four families with recurrent de novo variants c.1732C>T (p.Arg578Cys) and c.3436C>T (p.Arg1146Cys) in MAPK8IP3. The core phenotype includes spastic diplegia, intellectual disability, cerebral atrophy, and corpus callosum hypoplasia. Zebrafish embryos overexpressing human mutant JIP3 showed axon varicosities of the posterior lateral line nerve, suggesting an adverse effect on the developing axons. Our results suggest that MAPK8IP3 variants cause a neurodevelopmental disease. ANN NEUROL 2019;85:927–933..|
|51.||Positive effect of exogenous brain-derived neurotrophic factor on impaired neurite development and mitochondrial function in dopaminergic neurons derived from dental pulp stem cells from children with attention deficit hyperactivity disorder.|
|52.||Ryu Yanagisawa, Kazuyuki Matsuda, Shouichi Ohga, Hirokazu Kanegane, Akira Morimoto, Yasuhiro Okamoto, Akira Ohara, Keitaro Fukushima, Manabu Sotomatsu, Keiko Nomura, Akiko M. Saito, Keizo Horibe, Eiichi Ishii, Yozo Nakazawa, Correction to
Factors predicting the recurrence of Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children after treatment using the HLH-2004 protocol (International Journal of Hematology, (2019), 109, 5, (612-617), 10.1007/s12185-019-02612-2), International journal of hematology, 10.1007/s12185-019-02641-x, 109, 5, 2019.05, The correct name of the first author should be ‘‘Ryu Yanagisawa’’, and not ‘‘Ryu Yanagaisawa’’ as given in the original publication of the article..
|53.||Ryu Yanagaisawa, Kazuyuki Matsuda, Shouichi Ohga, Hirokazu Kanegane, Akira Morimoto, Yasuhiro Okamoto, Akira Ohara, Keitaro Fukushima, Manabu Sotomatsu, Keiko Nomura, Akiko M. Saito, Keizo Horibe, Eiichi Ishii, Yozo Nakazawa, Factors predicting the recurrence of Epstein–Barr virus-associated hemophagocytic lymphohistiocytosis in children after treatment using the HLH-2004 protocol, International journal of hematology, 10.1007/s12185-019-02612-2, 109, 5, 612-617, 2019.05, Epstein–Barr virus (EBV)-associated hemophagocytic lymphohistiocytosis (HLH) is highly prevalent in Japan. To date, no standard treatment for EBV–HLH has been established owing to the diversity in treatment response and the difficulty in assessing prognostic factors. The present prospective study recruited 27 children with EBV–HLH who were also part of the HLH-2004 study. EBV load in the peripheral blood was monitored at diagnosis and 2, 4, and 8 weeks after treatment initiation. Additionally, T-cell receptor (TCR) clonality and other laboratory data were evaluated. TCR clonality was positive in 14 patients at diagnosis. Seven of 27 patients experienced recurrences after treatment. No correlation was noted among any clinical data at diagnosis of patients with and without recurrence. However, the recurrence rate was significantly higher in patients aged < 2 years and/or those with a high plasma EBV load of > 103 copies/mL 2 weeks after treatment than that in patients without these factors. These findings suggest that a younger age or a high EBV load in plasma at the early phase of treatment is a factor predicting a recurrence and helps guide the intensity of subsequent treatment phases for children with EBV–HLH..|
|54.||Ryuichi Takemoto, Yoshitomo Motomura, Noriyuki Kaku, Yuko Ichimiya, Mamoru Muraoka, Shunsuke Kanno, Tamami Tanaka, Yasunari Sakai, Yoshihiko Maehara, Shouichi Ohga, Late-onset sepsis and encephalopathy after bicycle-spoke injury
A case report, BMC Infectious Diseases, 10.1186/s12879-019-4082-4, 19, 1, 2019.05, Background: Bicycle-spoke injuries rarely cause late complications of infection, including sepsis and sepsis-associated encephalopathy, with appropriate treatments. Case presentation: We experienced a 2-year-old girl who developed the signs of encephalopathy with fever 6 months after a spoke-injury. On admission, the injured skin was inflamed with cellulitis. The blood culture was positive for methicillin-sensitive Staphylococcus aureus. Electroencephalogram showed diffuse slow-wave activity. Diffusion-weighted magnetic resonance imaging detected a high-intensity lesion with decreased diffusivity at the right frontal cortex. She received immunoglobulin and combined antibiotics treatments in the intensive care unit, and successfully overcame the sepsis-associated encephalopathy without neurological impairments. Conclusion: This is the first report demonstrating that sepsis and its associated encephalopathy occurs in a remote period after the bicycle-spoke injury..
|55.||Ryota Souzaki, Naonori Kawakubo, Toshiharu Matsuura, Koichiro Yoshimaru, Yuhki Koga, Junkichi Takemoto, Yuichi Shibui, Kenichi Kohashi, Makoto Hayashida, Yoshinao Oda, Shouichi Ohga, Tomoaki Taguchi, Navigation surgery using indocyanine green fluorescent imaging for hepatoblastoma patients, Pediatric surgery international, 10.1007/s00383-019-04458-5, 35, 5, 551-557, 2019.05, Background: Technology for detecting liver tumors and identifying the bile ducts using indocyanine green (ICG) has recently been developed. However, the usefulness and limitations of ICG navigation surgery for hepatoblastoma (HB) have not been fully clarified. We herein report our experiences with surgical navigation using ICG for in HB patients. Methods: In 5 HB patients, 10 ICG navigation surgeries were performed using a 10-mm infrared fluorescence imaging scope after the injection of 0.5 mg/kg ICG intravenously. The surgical and clinical features were collected retrospectively. Results: Navigation surgery using ICG was performed for primary liver tumors in 4 cases, and the timing of ICG injection was 90.5 ± 33.7 h before the operation. All tumors exhibited intense fluorescence from the liver surface. ICG navigation for the primary liver tumor was useful for detecting the residual tumor at the stump and invasion to the diaphragm during surgery. Six lung surgeries using ICG navigation were performed. The timing of ICG injection was 21.8 ± 3.4 h before the operation. The size of the metastatic tumor was 7.4 ± 4.1 mm (1.2–15 mm). Of 11 metastatic tumors detected by computed tomography (CT), 10—including the smallest tumor (1.2 mm)—were able to be detected by ICG from the lung surface. The depth of the 10 ICG-positive tumors from the lung surface was 0.9 ± 1.9 mm (0–6 mm), and the depth of the single ICG-negative tumor was 12 mm. One lesion not detected by CT showed ICG false positivity. Conclusion: Navigation surgery using ICG for patients with HB was useful for identifying tumors and confirming complete resection. However, in ICG navigation surgery, we must be aware of the limitations with regard to the tumor size and the depth from the surface..|
|56.||Ryu Yanagisawa, Kazuyuki Matsuda, Shouichi Ohga, Hirokazu Kanegane, Akira Morimoto, Yasuhiro Okamoto, Akira Ohara, Keitaro Fukushima, Manabu Sotomatsu, Keiko Nomura, Akiko M Saito, Keizo Horibe, Eiichi Ishii, Yozo Nakazawa, Correction to: Factors predicting the recurrence of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in children after treatment using the HLH-2004 protocol., Int. J. Hematol., 10.1007/s12185-019-02641-x, 109, 5, 629, 2019.05, The correct name of the first author should be ''Ryu Yanagisawa'', and not ''Ryu Yanagaisawa'' as given in the original publication of the article..|
|57.||Kohara Hiroshi, Utsugisawa Taiju, Sakamoto Chika, Hirose Lisa, Ogawa Yoshie, Ogura Hiromi, Sugawara Ai, Liao Jiyuan, Aoki Takako, Iwasaki Takuya, Asai Takayoshi, Doisaki Sayoko, Okuno Yusuke, Muramatsu Hideki, Abe Takaaki, Kurita Ryo, Miyamoto Shohei, Sakuma Tetsushi, Shiba Masayuki, Yamamoto Takashi, Ohga Shouichi, Yoshida Kenichi, Ogawa Seishi, Ito Etsuro, Kojima Seiji, Kanno Hitoshi, Tani Kenzaburo, KLF1 mutation E325K induces cell cycle arrest in erythroid cells differentiated from congenital dyserythropoietic anemia patient-specific induced pluripotent stem cells, EXPERIMENTAL HEMATOLOGY, 10.1016/j.exphem.2019.03.001, 73, 25-37, 2019.05.|
|58.||Momoe Ohta, Yuko Noda, Mami Miyazono, Yuhki Koga, Miho Kifune, Masami Hamada, Tomoaki Taguchi, Shouichi Ohga, A survey on the status of countermeasures against anticancer drug exposure for families-focus on pediatric cancer hospitals, Japanese Journal of Cancer and Chemotherapy, 46, 4, 673-677, 2019.04, Safety measures against occupational exposure to anticancer drugs are practiced in line with guidelines; however, countermeasures against exposure for families in pediatric areas have not yet been considered. We investigated the recognition and practice of anticancer drug exposure measures for children and families by nurses working in pediatric cancer hospitals (15 facilities in total). The results suggest that the current situation of anticancer drug exposure measures, including family guidance, are not practiced adequately..|
|59.||Sayaka Okuzono, Ryoko Fukai, Marie Noda, Noriko Miyake, Sooyoung Lee, Noriyuki Kaku, Masafumi Sanefuji, Satoshi Akamine, Shunsuke Kanno, Yoshito Ishizaki, Hiroyuki Torisu, Ryutaro Kira, Naomichi Matsumoto, Yasunari Sakai, Shouichi Ohga, An acute encephalopathy with reduced diffusion in BRAF-associated cardio-facio-cutaneous syndrome, Brain and Development, 10.1016/j.braindev.2018.10.012, 41, 4, 378-381, 2019.04, Background: Cardio-facio-cutaneous syndrome (CFCS) is a rare genetic disorder characterized by cardiovascular anomalies, dysmorphic faces, ectodermal abnormalities and developmental delays. Mutations in BRAF and other RAS-MAPK pathway-associated genes are commonly identified in patients with CFCS. While this molecular pathway is known to be associated with neuro-inflammatory conditions, only one case with CFCS has been reported thus far to develop acute encephalopathy in childhood. Case report: A 3-year-old boy with dysmorphic features and mild psychomotor delay developed acute encephalopathy. After a 45-min long, generalized seizure, the magnetic resonance imaging revealed that the restricted diffusion signals spread to the bilateral subcortical white matters on day 1 of illness. Despite the 14 days of intensive care, the acute symptoms of encephalopathy left him intractable epilepsy and severe neurocognitive impairments. The whole-exome sequencing analysis identified a de novo heterozygous mutation of BRAF (NM_004333:p.Thr241Met) in this case. Conclusion: The present case suggests that the hyperactive condition of ERK signals might augment the development of acute encephalopathy and post-encephalopathic epilepsy in childhood..|
|60.||Tomoaki Taguchi, Yusuke Yanagi, Koichiro Yoshimaru, Xiu Ying Zhang, Toshiharu Matsuura, Koichi Nakayama, Eiji Kobayashi, Haruyoshi Yamaza, Kazuaki Nonaka, Shouichi Ohga, Takayoshi Yamaza, Regenerative medicine using stem cells from human exfoliated deciduous teeth (SHED)
a promising new treatment in pediatric surgery, Surgery today, 10.1007/s00595-019-01783-z, 49, 4, 316-322, 2019.04, Stem cells from human exfoliated deciduous teeth (SHEDs), being a type of mesenchymal stem cell, are an ideal cell source for regenerative medicine. They have minimal risk of oncogenesis, high proliferative capacity, high multipotency, and immunosuppressive ability. Stem cell transplantation using SHED has been found to have an anti-fibrotic effect on liver fibrosis in mice. SHED transplantation and the bio 3D printer, which can create scaffold-free 3-D images of the liver and diaphragm, provide a new innovative treatment modality for intractable pediatric surgical diseases such as biliary atresia and diaphragmatic hernia..
|61.||Naonori Kawakubo, Yoshiaki Kinoshita, Ryota Souzaki, Yuhki Koga, Utako Oba, Shouichi Ohga, Tomoaki Taguchi, The Influence of Sarcopenia on High-Risk Neuroblastoma, Journal of Surgical Research, 10.1016/j.jss.2018.10.048, 236, 101-105, 2019.04, Purpose: Sarcopenia is a syndrome that is defined by the loss of skeletal muscle mass, quality, and strength. In adult patients with malignancies, the presence of sarcopenia is known to be correlated with a poor prognosis; however, there have been no reports on the influence of sarcopenia on malignant tumors in pediatric patients. In the present study, we investigated whether or not sarcopenia affects the prognosis of high-risk neuroblastoma. Materials and methods: Thirteen patients with high-risk neuroblastoma who were treated according to the standard protocol at our hospital from 2007 to 2016 were divided into a progression-free survival group (n = 8) and a relapse/death group (n = 5). The rate of change in sarcopenia was calculated by comparing the psoas muscle area (PMA) of the L3-level lumbar spine on computed tomography before and after treatment with the standard protocol. The rate of change in the PMA, Kaup index, and serum albumin level were compared. Furthermore, we determined the cutoff rate of change in the PMA and compared the overall and progression-free survival. Results: The rates of change in the PMA were 1.24 and 0.84 in the progression-free survival and relapse/death groups, respectively (P = 0.0472). There were no significant differences in the rates of change in the Kaup index or the serum albumin level of the two groups. The patients whose rate of change in the PMA was >1.00 showed a prolonged overall (P = 0.0078) and progression-free survival (P = 0.006). Conclusions: A decrease in the skeletal muscle mass was suggested to be a significant prognostic factor for high-risk neuroblastoma..|
|62.||Yasunori Iida, Hiroyuki Wakiguchi, Fumiko Okazaki, Tamaki Nakamura, Hiroki Yasudo, Makoto Kubo, Kazuma Sugahara, Hiroshi Yamashita, Yutaka Suehiro, Naoko Okayama, Kunio Hashimoto, Naoki Iwamoto, Atsushi Kawakami, Yoshiharu Aoki, Hidetoshi Takada, Shoichi Ohga, Shunji Hasegawa, Early canakinumab therapy for the sensorineural deafness in a family with Muckle-Wells syndrome due to a novel mutation of NLRP3 gene, Clinical Rheumatology, 10.1007/s10067-018-4331-8, 38, 3, 943-948, 2019.03, Cryopyrin-associated periodic syndrome (CAPS) is one of the autoinflammatory disorders caused by mutations in NLRP3 gene. The over-production of interleukin (IL)-1β induced by NLRP3 gene mutations plays an important role in the pathophysiology of CAPS. We diagnosed 3 patients with CAPS, who were lineal family members having a novel mutation of NLRP3 gene. The objective of this report is to compare the characteristics of symptoms and differences in the therapeutic responses of them, who had the same mutation. In addition, we aimed to examine the usefulness of cytokine measurement for diagnosis or determination of treatment effect of CAPS. A 5-year-old Japanese boy (proband) came to our hospital because of short stature, reached the diagnosis of Muckle-Wells syndrome (MWS) due to a mutation in NLRP3 gene, which had not been reported so far (p.G328E, c.G983A). His mother and grandmother harbored the same mutation of NLRP3. We measured serum concentrations of cytokines in the proband assessed by flow-cytometric bead array. All of them had episodic skin eruptions with conjunctivitis, hearing loss, and arthralgia, but not periodic fever, cold-triggered episodes, and chronic aseptic meningitis. Only the proband had short stature. Canakinumab therapy led to a prompt relief of symptoms and normalized laboratory data in all patients. Audiograms demonstrated an improved hearing level in the proband, but not two others despite of the same mutation. All cytokines did not show any characteristic findings. Sensorineural hearing loss and itchless rash but not serum cytokine profile deserved attention to the diagnosis and treatment start of CAPS. The early intervention of IL-1β blockade may reduce the chance of complete deafness in patients with CAPS..|
|63.||Yasuaki Hagio, Akira Shiraishi, masataka ishimura, Motoshi Sonoda, Katsuhide Eguchi, Hidetaka Yamamoto, Yoshinao Oda, Shoichi Ohga, Posttransplant recipient-derived CD4
T-cell lymphoproliferative disease in X-linked hyper-IgM syndrome, Pediatric Blood and Cancer, 10.1002/pbc.27529, 66, 3, 2019.03.
|64.||Regenerative medicine using stem cells from human exfoliated deciduous teeth (SHED): a promising new treatment in pediatric surgery..|
|65.||Masako Ichiyama, Hirosuke Inoue, Masayuki Ochiai, masataka ishimura, Akira Shiraishi, Junko Fujiyoshi, Hironori Yamashita, Kazuo Sato, Shinya Matsumoto, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Shoichi Ohga, Diagnostic challenge of the newborn patients with heritable protein C deficiency, Journal of Perinatology, 10.1038/s41372-018-0262-0, 39, 2, 212-219, 2019.02, Objective: The diagnosis of neonatal-onset protein C (PC) deficiency is challenging. This study aimed to establish the neonatal screening of heritable PC deficiency in Japan. Study design: We determined the changes in plasma activity levels of PC and protein S (PS) in healthy neonates, and studied newborn patients with PROC mutation in the Japanese registry. Result: Physiological PC and PS levels increased with wide range. The PC/PS-activity ratios converged after birth. The PC/PS-activity ratios of 19 patients with biallelic mutations, but not, 9 with monoallelic mutation, were lower than those of 13 without mutation. The logistic regression analyses established a formula including two significant variables of PC activity (cut-off < 10%, odds ratio = 30.0) and PC/PS-activity ratio (cut-off < 0.35, odds ratio = 22.7), with 93% sensitivity and 44% specificity for determining patients with mutation(s). Conclusion: The PC/PS-activity ratio is an effective parameter for the genetic screening of neonatal-onset PC-deficiency in Japanese population..|
|66.||, Ryu Yanagisawa, Yozo Nakazawa, Kazuyuki Matsuda, Takahiro Yasumi, Hirokazu Kanegane, Shouichi Ohga, Akira Morimoto, Shoichi Ohga, Masue Imaizumi, Yasuhiro Okamoto, Akiko M. Saito, Keizo Horibe, Eiichi Ishii, Outcomes in children with hemophagocytic lymphohistiocytosis treated using HLH-2004 protocol in Japan, International journal of hematology, 10.1007/s12185-018-02572-z, 109, 2, 206-213, 2019.02, Recent advances in intensive chemo- and immunotherapy have contributed to the outcome of hemophagocytic lymphohistiocytosis (HLH); however, the prognosis of HLH in children differs by HLH subtype. In Japan, secondary HLH, particularly Epstein–Barr virus-associated HLH (EBV-HLH), is the most common HLH subtype. The prognosis of HLH has improved in recent years. We here conducted a prospective study of 73 patients who were treated with HLH-2004 protocol in Japan. EBV-HLH, familial HLH (FHL), and HLH of unknown etiology were seen in 41, 9, and 23 patients, respectively. Patients with resistant or relapsed disease after HLH-2004 treatment and those with FHL received hematopoietic stem cell transplantation (HSCT). The induction rate after initial therapy was 58.9%, and the 3-year overall survival (OS) rate of all patients was 73.9% and differed significantly among those with EBV-HLH, FHL, and HLH of unknown etiology. Of the 17 patients who received HSCT, the 3-year OS rates of those with and without complete resolution before HSCT were 83.3% and 54.5%, respectively. Outcomes in children with HLH who were treated with the same protocol differed among HLH subtypes. Appropriate strategy for each subtype should be established in future studies..|
|67.||Yasutaka Nakashima, Etsuro Nanishi, Kenichiro Yamamura, Kiyoshi Uike, Eiko Terashi, Yuichiro Hirata, Hazumu Nagata, Eiji Morihana, Tamami Tanaka, Satoshi Honjo, Hidetoshi Takada, Shoichi Ohga, Procalcitonin levels predicting the infliximab response of immunoglobulin resistant Kawasaki disease, Cytokine, 10.1016/j.cyto.2018.11.025, 114, 26-31, 2019.02, Objective: To search the predictive factors of infliximab resistance in intravenous immunoglobulin (IVIG)-resistant Kawasaki disease (KD) patients. Study design. Twenty-seven patients with KD who received infliximab after 4–5 g/kg of IVIG therapy from 2013 to 2015 were consecutively recruited in this study. They were divided into two groups: patients who responded to infliximab (infliximab-responsive group, n = 15) and patients who required additional therapy for the disease control (infliximab-resistant group, n = 12). We analyzed the clinical and laboratory parameters just before the infliximab treatment including serum levels of procalcitonin and cytokines with respect to the infliximab response. Results: Serum procalcitonin concentration (P = 0.017), neutrophils to lymphocytes ratio (P = 0.013), and % neutrophils (P = 0.004) were higher, and serum sodium concentration (P = 0.017) was lower in infliximab-resistant group than those of infliximab-responsive group, respectively. Multivariate logistic regression analyses indicated that higher procalcitonin concentration (odds ratio [OR] 1.48, 95% confidence interval [CI] 1.00–5.00, P = 0.046) and lower sodium levels (OR 0.64, 95% CI 0.32–1.00, P = 0.047), but not other variables, were associated with infliximab-resistance. Serum procalcitonin concentrations positively correlated with the serum levels of interleukin-6, soluble tumor necrosis factor receptor type 1 and type 2, respectively. Analyses of the receiver operating characteristic (ROC) curve showed that the cut-off value of procalcitonin 2.0 ng/ml had 58.3% of sensitivity and 93.3% of specificity. ROC analysis yielded an area under the curve (AUC) of 0.739 to predict infliximab-resistance. Conclusion: Serum procalcitonin might be an effective biomarker to predict infliximab resistance in severe KD patients who are refractory to IVIG treatment..|
|68.||Takahiro Kawahara, Junichiro Tezuka, Takahito Ninomiya, Satoshi Honjo, Natsuko Masumoto, Makiko Nanishi, Hideki Nakayama, Shoichi Ohga, Risk prediction of severe reaction to oral challenge test of cow’s milk, European Journal of Pediatrics, 10.1007/s00431-018-3274-z, 178, 2, 181-188, 2019.02, Cow’s milk is one of the most common food allergens among children. Oral food challenge tests determine the threshold dose of allergens, but have not been standardized. To reduce the severe reactions, we developed a practical model of the test. We studied 111 high-risk patients who underwent a first milk oral food challenge on the risk-stratified dose between 2011 and 2017 for predicting the severe reaction risk. Severe reactions were defined as showing > 3 of Sampson’s classification grade. Twenty-eight patients (25%) showed severe reactions without death. Prior to oral food challenge, severe reaction patients experienced milk avoidance (71% vs. 45%, p = 0.02) or bronchial asthma (61% vs. 28%, p = 0.003) more frequently and showed higher milk-specific IgE levels (median 28.3 vs. 7.7 U A /mL, p < 0.0001) than non-severe reaction patients. Multivariate logistic regression analyses established a formula including severe reaction-associated factors; increased levels of milk-specific IgE (odds ratio 11.61, p = 0.001), milk avoidance (odds ratio 3.88, p = 0.02), and bronchial asthma (odds ratio 3.75, p = 0.02). This model had 86% sensitivity and 56% specificity (cut-off 0.25) for risk. Five patients with < 25% probability developed severe reactions, which started in > 3 grade dyspnea up to 20 mL of challenge. Conclusion: This model could effectively reduce the severe reaction development on the first milk oral food challenge test according to the individual needs.What is Known:•Higher levels of milk-specific IgE values, bronchial asthma, and complete milk avoidance are independent risk factors of severe reactions during the cow’s milk oral food challenge.What is New:•Statistical analyses of our milk oral food challenge records for 111 patients helped us develop a model formula predicting severe reactions at the first test with high specificity and sensitivity.•This simple risk-stratified protocol is useful for minimizing the adverse events in the first milk challenge..|
|69.||Masako Ichiyama, Hirosuke Inoue, Masayuki Ochiai, Masataka Ishimura, Akira Shiraishi, Junko Fujiyoshi, Hironori Yamashita, Kazuo Sato, Shinya Matsumoto, Taeko Hotta, Takeshi Uchiumi, Dongchon Kang, Shouichi Ohga, Diagnostic challenge of the newborn patients with heritable protein C deficiency., Journal of perinatology : official journal of the California Perinatal Association, 10.1038/s41372-018-0262-0, 39, 2, 212-219, 2019.02, ABSTARCT: OBJECTIVE: The diagnosis of neonatal-onset protein C (PC) deficiency is challenging. This study aimed to establish the neonatal screening of heritable PC deficiency in Japan. STUDY DESIGN: We determined the changes in plasma activity levels of PC and protein S (PS) in healthy neonates, and studied newborn patients with PROC mutation in the Japanese registry. RESULT: Physiological PC and PS levels increased with wide range. The PC/PS-activity ratios converged after birth. The PC/PS-activity ratios of 19 patients with biallelic mutations, but not, 9 with monoallelic mutation, were lower than those of 13 without mutation. The logistic regression analyses established a formula including two significant variables of PC activity (cut-off < 10%, odds ratio = 30.0) and PC/PS-activity ratio (cut-off < 0.35, odds ratio = 22.7), with 93% sensitivity and 44% specificity for determining patients with mutation(s). CONCLUSION: The PC/PS-activity ratio is an effective parameter for the genetic screening of neonatal-onset PC-deficiency in Japanese population..|
|70.||, Hiroaki Kurata, Masayuki Ochiai, Hirosuke Inoue, Masako Ichiyama, Kazuaki Yasuoka, Junko Fujiyoshi, Yuki Matsushita, Satoshi Honjo, Yasunari Sakai, Shoichi Ohga, A nationwide survey on tracheostomy for very-low-birth-weight infants in Japan, Pediatric Pulmonology, 10.1002/ppul.24200, 54, 1, 53-60, 2019.01, Objectives: Tracheostomy is indicated for very-low-birth-weight infants (VLBWIs) with prolonged respiratory problems during the perinatal period. The objective of this study is to clarify the epidemiology and risk factors in VLBWIs with tracheostomy after birth in Japan. Methods: A total of 40 806 VLBWIs were registered in the Neonatal Research Network of Japan database from 2003 to 2012. Among them, 34 674 infants (85%) survived over 28 days after birth and were subjected to this study. The clinical variables at birth, outcomes at hospital discharge and associated factors for tracheostomy were examined. Results: The proportion of VLBWIs with tracheostomy did not increase during the study period (mean 36 cases per year, 0.93%). The rate of in-hospital death over 28 days after birth did not differ between tracheostomized and non-tracheostomized infants (2/324, 0.6% vs 314/34 350, 0.9%). Tracheostomized infants more frequently had severe or moderate bronchopulmonary dysplasia (BPD) (75.5% vs 26.0%, P < 0.01) and longer hospitalization (229 days vs 83 days, P < 0.01) than non-tracheostomized infants. Tracheostomized patients showed higher comorbidities with hypoxic ischemic encephalopathy (odds ratio [OR] 10.98, P < 0.01), muscular disease (OR 10.95, P < 0.01), severe or moderate BPD (OR 7.79, P < 0.01), chromosomal abnormality (OR 4.43, P < 0.01) or sepsis (OR 1.78, P < 0.05) at hospital discharge than non-tracheostomized patients. Conclusion: We demonstrated the non-increasing rate in tracheostomy for VLBWIs and such cases were associated with an excellent survival in Japan. These data provide evidence that more attentive care must be practiced in order to reduce the pulmonary and neuromuscular burdens of VLBWIs at birth..|
|71.||Kousuke Yonemoto, Yuko Shono, Masafumi Sanefuji, Noriyuki Kaku, Ayumi Sakata, Rieko Baba, Fumiya Yamashita, Satoshi Akamine, Michiko Torio, Yoshito Ishizaki, Yoshihiko Maehara, Yasunari Sakai, Shoichi Ohga, Early Intervention With Adrenocorticotropin for Acute Encephalopathy-Associated Epileptic Spasms
Report of Two Cases, Clinical EEG and Neuroscience, 10.1177/1550059418786381, 50, 1, 51-55, 2019.01, Purpose. Acute encephalopathy with biphasic seizures and reduced diffusion (AESD) is a leading cause of childhood-onset encephalopathy in Japan. Children with AESD frequently develop intractable epilepsy, whereas their treatment options remain to be determined. Method. We present 2 unrelated girls, who developed AESD at 25 months (case 1) and 12 months of age (case 2). Both cases underwent intensive cares from the first day of illness, whereas severe neurological impairments were left on discharge. They showed repeated signs of epileptic spasms at 2 months (case 1) and 8 months (case 2) after the onset of AESD. Video-monitoring electroencephalograms (EEG) detected the recurrent attacks accompanying slow-wave bursts and transient suppressions of the precedent epileptiform discharges, as typically observed in epileptic spasms. Results. Intramuscular injection of adrenocorticotropic hormone (ACTH, 0.0125 mg/kg/d) was introduced within 1 month from the onset of epileptic spasms and continued for 2 weeks. The ACTH treatment disrupted the paroxysmal activity in EEG, and it has relieved these patients from epileptic seizures for more than 1 year. Conclusion. This report illustrates the potential efficacy of ACTH for a group of children with epileptic spasms after AESD..
|72.||Kay Tanita, Akihiro Hoshino, Ken Ichi Imadome, Takahiro Kamiya, Kento Inoue, Tsubasa Okano, Tzu wen Yeh, Masakatsu Yanagimachi, Akira Shiraishi, masataka ishimura, Tilmann Schober, Meino Rohlfs, Masatoshi Takagi, Kohsuke Imai, Hidetoshi Takada, Shoichi Ohga, Christoph Klein, Tomohiro Morio, Hirokazu Kanegane, Epstein-Barr virus-associated γδ T-cell lymphoproliferative disorder associated with hypomorphic IL2RG mutation, Frontiers in Pediatrics, 10.3389/fped.2019.00015, 7, FEB, 2019.01, Chronic active Epstein-Barr virus (EBV) infection (CAEBV) is an EBV-associated lymphoproliferative disease characterized by repeated or sustainable infectious mononucleosis (IM)-like symptoms. EBV is usually detected in B cells in patients who have IM or Burkitt's lymphoma and even in patients with X-linked lymphoproliferative syndrome, which is confirmed to have vulnerability to EBV infection. In contrast, EBV infects T cells (CD4+ T, CD8+ T, and γδT) or NK cells mono- or oligoclonally in CAEBV patients. It is known that the CAEBV phenotypes differ depending on which cells are infected with EBV. CAEBV is postulated to be associated with a genetic immunological abnormality, although its cause remains undefined. Here we describe a case of EBV-related γδT-cell proliferation with underlying hypomorphic IL2RG mutation. The immunological phenotype consisted of γδT-cell proliferation in the peripheral blood. A presence of EBV-infected B cells and γδT cells mimicked γδT-cell-type CAEBV. Although the patient had normal expression of CD132 (common γ chain), the phosphorylation of STAT was partially defective, indicating impaired activation of the downstream signal of the JAK/STAT pathway. Although the patient was not diagnosed as having CAEBV, this observation shows that CAEBV might be associated with immunological abnormality..|
|73.||Yuko Shono, Motoshi Sonoda, masataka ishimura, Shunsuke Kanno, Shoichi Ohga, Hemorrhagic Pneumonia as the First Manifestation of Anhidrotic Ectodermal Dysplasia with Immunodeficiency, Journal of Clinical Immunology, 10.1007/s10875-019-00626-3, 2019.01.|
|74.||Hazumu Nagata, Eiko Terashi, Mamoru Muraoka, Kiyoshi Uike, Yuichiro Hirata, Hideki Tatewaki, Yasuyuki Fujita, Kenichiro Yamamura, Shoichi Ohga, High incidence of ductal closure or narrowing at birth in patients with right ventricular outflow tract obstruction with normal orientation of the ductus arteriosus, Cardiology in the Young, 10.1017/S1047951118001798, 29, 1, 54-58, 2019.01, Background Ductal patency is mandatory to manage patients with ductal-dependent pulmonary circulation. The aim of this study is to elucidate the morphological and haemodynamic features of ductus arteriosus with right ventricular outflow tract obstruction, and investigate the appropriate perinatal management.Patients and methods Patients with prenatal diagnosis of right ventricular outflow tract obstruction at our institution between 2010 and 2015 were included in the study. Reverse orientation of the ductus arteriosus is defined as an inferior angle of 90° at the aortic junction, and normal orientation of the ductus arteriosus as an angle of >90°. We retrospectively reviewed the shape and flow pattern of ductus arteriosus and the clinical characteristics of the cases.Results A total of 39 patients were enrolled. The shape was divided into normal orientation (n=15) and reverse orientation (n=24) of the ductus arteriosus. There was no significant difference in the type of oxygen saturation at birth and age at shunt operation between both the groups. However, the median narrowest diameter of ductus arteriosus in the normal orientation group was significantly smaller than that in the reverse orientation group (2.0 [1.0-5.4] versus 3.0 [1.3-4.4] mm, p0.05). In two patients of the normal orientation group, ductus arteriosus had closed at birth, and one of whom died because of severe cyanosis.Conclusions Normal orientation pattern might have high incidence of an early narrowing or closure of ductus arteriosus at birth. The critical patients need careful evaluation by repeated foetal echocardiography and further maternal interventions..|
|75.||Huong Thi Nguyen Nguyen, Hiroki Kato, Hiroshi Sato, Haruyoshi Yamaza, Yasunari Sakai, Shoichi Ohga, Kazuaki Nonaka, Keiji Masuda, Positive effect of exogenous brain-derived neurotrophic factor on impaired neurite development and mitochondrial function in dopaminergic neurons derived from dental pulp stem cells from children with attention deficit hyperactivity disorder, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2019.04.084, 2019.01, Attention deficit hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders and is characterized by impaired attention, hyperactivity, and impulsivity. While multiple etiologies are implicated in ADHD, its underlying mechanism(s) remain unclear. Although previous studies have suggested dysregulation of dopaminergic signals, mitochondria, and brain-derived neurotrophic factor (BDNF) in ADHD, few studies have reported these associations directly. Stem cells from human exfoliated deciduous teeth (SHED) can efficiently differentiate into dopaminergic neurons (DNs) and are thus a useful disease-specific cellular model for the study of neurodevelopmental disorders associated with DN dysfunction. This study aimed to elucidate the relationships between DNs, mitochondria, and BDNF in ADHD by analyzing DNs differentiated from SHED obtained from three boys with ADHD and comparing them to those from three typically developing boys. In the absence of exogenous BDNF in the cell culture media, DNs derived from boys with ADHD (ADHD-DNs) exhibited impaired neurite outgrowth and branching, decreased mitochondrial mass in neurites, and abnormal intracellular ATP levels. In addition, BDNF mRNA was significantly decreased in ADHD-DNs. Supplementation with BDNF, however, significantly improved neurite development and mitochondrial function in ADHD-DNs. These results suggest that ADHD-DNs may have impaired neurite development and mitochondrial function associated with insufficient production of BDNF, which may be improved by exogenous BDNF supplementation. Findings such as these, from patient-derived SHED, may contribute to the future development of treatment strategies for aberrant dopaminergic signaling, mitochondrial functioning, and BDNF levels implicated in ADHD pathogenesis..|
|76.||Masafumi Sanefuji, Hiroshi Yamashita, Michiko Torio, Daisuke Katsuki, Satoshi Akamine, Yoshito Ishizaki, Junji Kishimoto, Yasunari Sakai, Hidetoshi Takada, Keiko Yoshida, Shoichi Ohga, A rightward saccade to an unexpected stimulus as a marker for lateralised visuospatial attention /631/378/2649/1310 /631/378/2617/1795 /631/477/2811 article, Scientific reports, 10.1038/s41598-018-25890-y, 8, 1, 2018.12, The human brain is lateralised to the right for visuospatial attention, particularly when reorienting attention to unexpected stimuli. However, the developmental characteristics of lateralisation remain unclear. To address this question, we devised a saccade task applicable for both adults and children. To assess the utility of this system, we investigated the correlation between line bisection test performance and the saccade task for 54 healthy adult volunteers. Participants followed a visual target that jumped 10 times, alternating between two fixed positions across the midline with a constant pace. In both the rightward and leftward directions, saccadic reaction time (RT) to the target jump decreased and reached a plateau from the first to the tenth jumps. Furthermore, we obtained the time required for reorienting in the contralateral hemisphere using the corrected value of the first RT. We found that longer corrected RTs in the rightward saccade were associated with greater deviation to the left in the line bisection task. This correlation was not observed for leftward saccades. Thus, corrected RTs in rightward saccades reflected the strength of individual hemispheric lateralisation. In conclusion, the rightward saccade task provides a suitable marker for lateralised visuospatial attention, and for investigating the development of lateralisation..|
|77.||Huong Thi Nguyen Nguyen, Hiroki Kato, Keiji Masuda, Haruyoshi Yamaza, Yuta Hirofuji, Hiroshi Sato, Thanh Thi Mai Pham, Fumiko Takayama, Yasunari Sakai, Shoichi Ohga, Tomoaki Taguchi, Kazuaki Nonaka, Impaired neurite development associated with mitochondrial dysfunction in dopaminergic neurons differentiated from exfoliated deciduous tooth-derived pulp stem cells of children with autism spectrum disorder, Biochemistry and Biophysics Reports, 10.1016/j.bbrep.2018.09.004, 16, 24-31, 2018.12, Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder characterized by impaired social interactions, restrictive interests, and repetitive stereotypic behaviors. Among the various mechanisms underlying the pathogenesis of ASD, dysfunctions of dopaminergic signaling and mitochondria have been hypothesized to explain the core symptoms of children with ASD. However, only a few studies focusing on the pathological association between dopaminergic neurons (DN) and mitochondria in ASD have been performed using patient-derived stem cells and in vitro differentiated neurons. Stem cells from human exfoliated deciduous teeth (SHED) are neural crest-derived mesenchymal stem cells present in the dental pulp of exfoliated deciduous teeth; these cells can differentiate into dopaminergic neurons (DN) in vitro. This study aimed to investigate the pathological association between development of DN and mitochondria in ASD by using SHED as a disease- or patient-specific cellular model. The SHED obtained from three children with ASD and three typically developing children were differentiated into DN, and the neurobiology of these cells was examined. The DN derived from children with ASD showed impaired neurite outgrowth and branching, associated with decreased mitochondrial membrane potential, ATP production, number of mitochondria within the neurites, amount of mitochondria per cell area and intracellular calcium level. In addition, impaired neurite outgrowth and branching of ASD-derived DN were not improved by brain-derived neurotrophic factor (BDNF), suggesting impairment of the BDNF signaling pathway in ASD. These results imply that intracerebral dopamine production may have decreased in these children. The earliest age at which deciduous teeth spontaneously exfoliate in humans, and SHED can be noninvasively collected, is approximately 6 years. Our results suggest that in vitro analysis of SHED-derived DN obtained from children with ASD provides neurobiological information that may be useful in determining treatment strategies in the early stages of ASD..|
|78.||Hirosuke Inoue, Masayuki Ochiai, Yasunari Sakai, Kazuaki Yasuoka, Koichi Tanaka, Masako Ichiyama, Hiroaki Kurata, Junko Fujiyoshi, Yuki Matsushita, Satoshi Honjo, Kazuaki Nonaka, Tomoaki Taguchi, Kiyoko Kato, Shoichi Ohga, Neurodevelopmental outcomes in infants with birth weight ≤500 g at 3 years of age, Pediatrics, 10.1542/peds.2017-4286, 142, 6, 2018.12, OBJECTIVES: To determine neurodevelopmental outcomes at 3 years of age in children born with a birth weight (BW) of ≤500 g. METHODS: Infants who were born with a BW of ≤500 g from 2003 to 2012 in the Neonatal Research Network of Japan and survived to discharge from the NICU were eligible in this study. The study population consisted of 460 children (56.7% of 811 surviving infants) who were evaluated at 36 to 42 months of age. Neurodevelopmental impairment (NDI) was defined as having cerebral palsy, visual impairment, hearing impairment, or a developmental quotient score of <70. RESULTS: The overall proportion of NDI was 59.1% (95% confidence interval [CI]: 54.6%-63.5%). The trend revealed no significant change during the study period. In a multivariate modified Poisson regression analysis, NDI was associated with severe intraventricular hemorrhage (adjusted risk ratio [RR]: 1.42; 95% CI: 1.19-1.68; P <.01), cystic periventricular leukomalacia (adjusted RR: 1.40; 95% CI: 1.13-1.73; P <.01), severe necrotizing enterocolitis (adjusted RR: 1.31; 95% CI: 1.07-1.60; P <.01), surgical ligation for patent ductus arteriosus (adjusted RR: 1.29; 95% CI: 1.09-1.54; P <.01), and male sex (adjusted RR: 1.19; 95% CI: 1.01-2.40; P =.04). CONCLUSIONS: This cohort showed that neurodevelopmental outcomes of infants with a BW of ≤500 g have not improved from 2003 to 2012. Multivariate analysis revealed that severe intracranial hemorrhage and cystic periventricular leukomalacia were the strongest risk factors for NDIs. Our data suggested that measures aimed at reducing neurologic morbidities will be important for improving outcomes of infants with a BW of ≤500 g..|
|79.||Seiichi Morokuma, Takehiro Michikawa, Kiyoko Kato, Masafumi Sanefuji, Eiji Shibata, Mayumi Tsuji, Ayako Senju, Toshihiro Kawamoto, Shoichi Ohga, Koichi Kusuhara, Non-reassuring foetal status and neonatal irritability in the Japan Environment and Children’s Study
A cohort study, Scientific reports, 10.1038/s41598-018-34231-y, 8, 1, 2018.12, The aim of this study was to investigate whether non-reassuring foetal status (NRFS) affected an infant’s temperament, or if the temperament formed prenatally resulted in an excessive heart rate reaction that was diagnosed as NRFS. We examined the correlation between NRFS and difficulty in holding a baby, and the amount of crying in the one month after birth, which was considered an indicator of the newborn’s temperament. We divided the cases with NRFS into positive NRFS and false positive NRFS. NRFS was associated with bad mood, frequent crying for a long duration, and intense crying. After adjustment for other covariates, NRFS was associated with bad mood (odds ratio, OR = 1.15, 95% confidence interval, CI = 1.00–1.33), and intense crying (1.12, 1.02–1.24). In the multi-variable model, positive and false positive NRFS were not clearly associated with neonatal irritability. When stratified by parity, NRFS and false positive NRFS were likely to be positively associated with neonatal irritability in parous women. The clear association between NRFS and intense crying was observed in parous women (multi-variable adjusted OR = 1.46, 95% CI = 1.16–1.83), but not in nulliparae (1.01, 0.91–1.12) (p for effect modification <0.01). Similarly, increased odds of intense crying associated with false positive NRFS were only found in parous women (multi-variable adjusted OR = 1.40, 95% CI = 1.09–1.81) (p for effect modification = 0.03). There was no association observed between positive NRFS and irritability; therefore, NRFS has no effect on an infant’s temperament..
|80.||Naho Morisaki, Chie Nagata, Shinobu Yasuo, Seiichi Morokuma, Kiyoko Kato, Masafumi Sanefuji, Eiji Shibata, Mayumi Tsuji, Ayako Senju, Toshihiro Kawamoto, Shoichi Ohga, Koichi Kusuhara, Optimal protein intake during pregnancy for reducing the risk of fetal growth restriction
The Japan Environment and Children's Study, British Journal of Nutrition, 10.1017/S000711451800291X, 120, 12, 1432-1440, 2018.12, Clinical trials show that protein supplement increases infant size in malnourished populations; however, epidemiological studies in high-income countries have reported mixed results. Although these findings suggest a non-linear relationship between maternal macronutrient intake and fetal growth, this relationship has not been closely examined. We assessed the association between maternal protein intake and fetal growth among 91 637 Japanese women with singletons in a nation-wide cohort study using validated FFQ. The respondents answered the FFQ twice, once during early pregnancy (FFQ1; 16·3 (sd 6·0) weeks), and second during mid-pregnancy (FFQ2, 28·1 (sd 4·1) weeks). Daily energy intake and percentage energy from protein, fats and carbohydrates were 7477 (sd 2577) kJ and 13·5 (sd 2·0), 29·5 (sd 6·5) and 55·3 (sd 7·8) %, respectively, for FFQ1, and 7184 (sd 2506) kJ and 13·6 (sd 2·1), 29·8 (sd 6·6) and 55·3 (sd 7·9) %, respectively, for FFQ2. The average birth weight was 3028 (sd 406) g, and 6350 infants (6·9 %) were small for gestational age (SGA). In both phases of the survey, birth weight was highest and the risk of SGA was lowest when the percentage energy from protein was 12 %, regardless of whether isoenergetic replacement was with fat or carbohydrates. Furthermore, when protein density in the maternal diet was held constant, birth weight was highest when 25 % of energy intake came from fat and 61 % came from carbohydrates during early pregnancy. We found maternal protein intake to have an inverse U-curve relationship with fetal growth. Our results strongly suggest that the effect of protein on birth weight is non-linear, and that a balanced diet fulfilling the minimum requirement for all macronutrients was ideal for avoiding fetal growth restriction..
|81.||Yuka Matsunaga, masataka ishimura, Hazumu Nagata, Kiyoshi Uike, Tadamune Kinjo, Masayuki Ochiai, Kenichiro Yamamura, Hidetoshi Takada, Yoshihisa Tanoue, Masaki Hayakawa, Masanori Matsumoto, Toshiro Hara, Shoichi Ohga, Thrombotic microangiopathy in a very young infant with mitral valvuloplasty, Pediatrics and Neonatology, 10.1016/j.pedneo.2018.02.002, 59, 6, 595-599, 2018.12, Background: Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by systemic or intrarenal platelet aggregation, thrombocytopenia, and red cell fragmentation. Post-operative TMA mostly occurs in adult patients with cardiovascular surgery, with the distinct pathophysiology from classical thrombotic thrombocytopenic purpura (TTP) although the exact pathophysiology remains unclear. Case presentation: A one-month-old infant developed TMA after the initial surgery of double outlet right ventricle. ADAM metallopeptidase with thrombospondin type 1 motif 13 (ADAMTS13) activity was sustained (64%) with the undetectable inhibitor. Von Willebrand factor (VWF) multimer analyses showed absent high-molecular weight multimers. Echocardiography disclosed severe mitral regurgitation. The mitral valve repair 32 days after the initial valvuloplasty led to prompt resolution of TMA. These suggested that TMA occurred in association with valvulopathy-triggered turbulent shear flow, mechanical hemolysis and endothelial damage. The consumption of large VWF multimers might account for the vascular high shear stress shown in Heyde syndrome. Conclusion: The youngest case of post-operative TMA underscores the critical coagulopathy after the first surgical intervention for congenital heart disease..|
|82.||Masafumi Sanefuji, Yuko Shono, Noriyuki Kaku, Momoko Sasazuki, Kosuke Yonemoto, Michiko Torio, Soichi Mizuguchi, Yoshitomo Motomura, Mamoru Muraoka, Sooyoung Lee, Haruhisa Baba, Kazuhiro Okubo, Yuri Sonoda, Yoshito Ishizaki, Yasunari Sakai, Shoichi Ohga, Vascular pathomechanism in acute encephalopathy with biphasic seizures and late reduced diffusion, Journal of the Neurological Sciences, 10.1016/j.jns.2018.10.007, 395, 141-146, 2018.12, Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a childhood-onset encephalopathy, but the precise pathophysiology remains unclear. We encountered a child with Moyamoya syndrome and AESD. He exhibited left-predominant stenosis of the middle cerebral artery (MCA), and later developed broad lesions in the left hemisphere, raising the possibility that insufficient blood supply relates to formation of the lesions. To test the hypothesis, we investigated the relationship between MCA volume and lesion extent in seven AESD children without preexisting diseases. The MCA volume and lesion extent were quantified with time of flight images for construction of magnetic resonance angiography and apparent diffusion coefficient maps, respectively. Lateralization indices ([right − left]/[right + left]) of the MCA volume and lesion extent were calculated. We found that the lateralization indices were negatively correlated (r = −0.786, p =.036), that is, when the MCA volume was smaller in one side than the other side, the lesions were likely to develop more extensively in the ipsilateral side than the contralateral side. This indicates the association of insufficient blood supply with the lesions. The present study provides the first observation to suggest the involvement of vascular mechanism in AESD and has potential implications for novel therapeutic approach..|
|83.||Masafumi Sanefuji, Hiroshi Yamashita, Michiko Torio, Daisuke Katsuki, Satoshi Akamine, Yoshito Ishizaki, Junji Kishimoto, Yasunari Sakai, Hidetoshi Takada, Keiko Yoshida, Shouichi Ohga, A rightward saccade to an unexpected stimulus as a marker for lateralised visuospatial attention /631/378/2649/1310 /631/378/2617/1795 /631/477/2811 article, Scientific Reports, 10.1038/s41598-018-25890-y, 8, 1, 2018.12, The human brain is lateralised to the right for visuospatial attention, particularly when reorienting attention to unexpected stimuli. However, the developmental characteristics of lateralisation remain unclear. To address this question, we devised a saccade task applicable for both adults and children. To assess the utility of this system, we investigated the correlation between line bisection test performance and the saccade task for 54 healthy adult volunteers. Participants followed a visual target that jumped 10 times, alternating between two fixed positions across the midline with a constant pace. In both the rightward and leftward directions, saccadic reaction time (RT) to the target jump decreased and reached a plateau from the first to the tenth jumps. Furthermore, we obtained the time required for reorienting in the contralateral hemisphere using the corrected value of the first RT. We found that longer corrected RTs in the rightward saccade were associated with greater deviation to the left in the line bisection task. This correlation was not observed for leftward saccades. Thus, corrected RTs in rightward saccades reflected the strength of individual hemispheric lateralisation. In conclusion, the rightward saccade task provides a suitable marker for lateralised visuospatial attention, and for investigating the development of lateralisation..|
|84.||Impaired neurite development associated with mitochondrial dysfunction in dopaminergic neurons differentiated from exfoliated deciduous tooth-derived pulp stem cells of children with autism spectrum disorder..|
|85.||Hirosuke Inoue, Masayuki Ochiai, Yasunari Sakai, Kazuaki Yasuoka, Koichi Tanaka, Masako Ichiyama, Hiroaki Kurata, Junko Fujiyoshi, Yuki Matsushita, Satoshi Honjo, Kazuaki Nonaka, Tomoaki Taguchi, Kiyoko Kato, Shouichi Ohga, Neurodevelopmental Outcomes in Infants With Birth Weight ≤500 g at 3 Years of Age., Pediatrics, 10.1542/peds.2017-4286, 142, 6, 2018.12, OBJECTIVES: To determine neurodevelopmental outcomes at 3 years of age in children born with a birth weight (BW) of ≤500 g. METHODS: Infants who were born with a BW of ≤500 g from 2003 to 2012 in the Neonatal Research Network of Japan and survived to discharge from the NICU were eligible in this study. The study population consisted of 460 children (56.7% of 811 surviving infants) who were evaluated at 36 to 42 months of age. Neurodevelopmental impairment (NDI) was defined as having cerebral palsy, visual impairment, hearing impairment, or a developmental quotient score of <70. RESULTS: The overall proportion of NDI was 59.1% (95% confidence interval [CI]: 54.6%-63.5%). The trend revealed no significant change during the study period. In a multivariate modified Poisson regression analysis, NDI was associated with severe intraventricular hemorrhage (adjusted risk ratio [RR]: 1.42; 95% CI: 1.19-1.68; P < .01), cystic periventricular leukomalacia (adjusted RR: 1.40; 95% CI: 1.13-1.73; P < .01), severe necrotizing enterocolitis (adjusted RR: 1.31; 95% CI: 1.07-1.60; P < .01), surgical ligation for patent ductus arteriosus (adjusted RR: 1.29; 95% CI: 1.09-1.54; P < .01), and male sex (adjusted RR: 1.19; 95% CI: 1.01-2.40; P = .04). CONCLUSIONS: This cohort showed that neurodevelopmental outcomes of infants with a BW of ≤500 g have not improved from 2003 to 2012. Multivariate analysis revealed that severe intracranial hemorrhage and cystic periventricular leukomalacia were the strongest risk factors for NDIs. Our data suggested that measures aimed at reducing neurologic morbidities will be important for improving outcomes of infants with a BW of ≤500 g..|
|86.||Takashi Furuta, Shunji Hasegawa, Makoto Mizutani, Takashi Iwai, Noriko Ohbuchi, Shoji Kawano, Norimichi Tashiro, Masashi Uchida, Masanari Hasegawa, Masashi Motoyama, Takaomi Sekino, Kenji Nakatsuka, Kiyoshi Ichihara, Komei Shirabe, Shoichi Ohga, Burden of Human Metapneumovirus and Respiratory Syncytial Virus Infections in Asthmatic Children, The Pediatric infectious disease journal, 10.1097/INF.0000000000002038, 37, 11, 1107-1111, 2018.11, BACKGROUND: Human metapneumovirus (hMPV) and respiratory syncytial virus (RSV) are the leading causes of acute respiratory illness in children. Clinical burden of each infection on the respiratory distress in asthmatic patients remains unclear. The purpose of the study was to clarify the effect of these infections on the severity of asthmatic children in the seasonal outbreaks.
METHODS: A total of 1,217 pediatric inpatients with hMPV (n = 114) or RSV (n = 1,103) infection in Yamaguchi prefecture, Japan, between 2011 and 2014 were enrolled. Bronchial asthma was defined as having more than 3 episodes of wheezing illness over 1 year of age. Infection was determined by the positive antigen test for each virus in the nasal specimens.
RESULTS: The number of patients peaked at age 12-15 months in hMPV infection and at age 0-3 months in RSV infection. The proportion of hypoxic patients (40-50%) did not differ at any age between hMPV-infected and RSV-infected children. In the analysis of date from > 1 year old patients with hypoxia, hMPV-infection group was older (P = 0.036), and more frequently had history of asthma (P = 0.015) or abnormal chest roentgenogram (P < 0.001) than RSV-infection group. Multivariate analysis indicated that the hypoxia-associated factors were history of asthma in both hMPV (odds ratio [OR]: 15.8; P < 0.001) and RSV infections (OR, 2.2; P = 0.005), higher body temperature in hMPV infection (OR, 2.2; P = 0.009), and younger age in RSV infection (OR, 1.4; P = 0.004).
CONCLUSIONS: Outbreaks of hMPV, rather than, RSV infection may have a greater impact on the development of hypoxic respiratory illness in asthmatic children..
|87.||Yusaku Nagatomo, Jun Muneuchi, Yasutaka Nakashima, Etsuro Nanishi, Hiromitsu Shirozu, Mamie Watanabe, Kiyoshi Uike, Hazumu Nagata, Yuichiro Hirata, Kenichiro Yamamura, Yasuhiko Takahashi, Seigo Okada, Yasuo Suzuki, Shunji Hasegawa, Shoichi Ohga, Effective infliximab therapy for the early regression of coronary artery aneurysm in Kawasaki disease, International Journal of Cardiology, 10.1016/j.ijcard.2018.04.062, 271, 317-321, 2018.11, Background: There is limited information available regarding the role of infliximab (IFX) following the acute phase of Kawasaki disease (KD). We aimed to evaluate whether IFX is associated with coronary artery aneurysm (CAA) regression. Methods: Between 2005 and 2016, we identified 971 consecutive patients with KD from 3 tertiary institutions, and 49 (5%) with CAAs were enrolled in our study. Patients were divided into 2 groups: 27 who received IFX and 22 who did not. The persistence rate of CAAs was compared between the groups. Results: Age, sex, and duration of the febrile period did not significantly differ between the groups. The maximum value of C-reactive protein was higher in the IFX- than in the non-IFX group. The maximum z-score of CAAs did not differ between the groups. The 2-, 4- and 6-year cumulative persistence rate of CAA was 24%, 24% and 24% in IFX-group, whereas 67%, 52% and 33% in non-IFX group, respectively (P = 0.03). The median duration of CAA regression was 1.1 vs. 4.6 years. Among those who developed medium- or large-sized CAAs, the 2-, 4- and 6-year cumulative persistence rate of CAA was 33%, 33% and 33% in IFX group, whereas 77%, 51% and 48% in non-IFX group, respectively (P = 0.047). Multivariate logistic regression analysis indicated that the maximum z-score (hazard ratio 0.72, p < 0.001) and response to IFX (hazard ratio 4.56, p = 0.017) were independently related to regression. Conclusion: IFX therapy was observed to be effective for the early improvement of CAAs in patients with intravenous immunoglobulin-resistant KD..|
|88.||Takashi Imai, Takayuki Matsumura, Sabine Mayer-Lambertz, Christine A. Wells, Eri Ishikawa, Suzanne K. Butcher, Timothy C. Barnett, Mark J. Walker, Akihiro Imamura, Hideharu Ishida, Tadayoshi Ikebe, Tomofumi Miyamoto, Manabu Ato, Shoichi Ohga, Bernd Lepenies, Nina M. Van Sorge, Sho Yamasaki, Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection, Proceedings of the National Academy of Sciences of the United States of America, 10.1073/pnas.1809100115, 115, 45, E10662-E10671, 2018.11, Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes a range of diseases, including fatal invasive infections. However, the mechanisms by which the innate immune system recognizes GAS are not well understood. We herein report that the C-type lectin receptor macrophage inducible C-type lectin (Mincle) recognizes GAS and initiates antibacterial immunity. Gene expression analysis of myeloid cells upon GAS stimulation revealed the contribution of the caspase recruitment domain-containing protein 9 (CARD9) pathway to the antibacterial responses. Among receptors signaling through CARD9, Mincle induced the production of inflammatory cytokines, inducible nitric oxide synthase, and reactive oxygen species upon recognition of the anchor of lipoteichoic acid, monoglucosyldiacylglycerol (MGDG), produced by GAS. Upon GAS infection, Mincle-deficient mice exhibited impaired production of proinflammatory cytokines, severe bacteremia, and rapid lethality. GAS also possesses another Mincle ligand, diglucosyldiacylglycerol; however, this glycolipid interfered with MGDG-induced activation. These results indicate that Mincle plays a central role in protective immunity against acute GAS infection..|
|89.||Kentaro Nakashima, Yuhki Koga, Yasunari Sakai, Hidetoshi Takada, Katsumi Harimaya, Ohga Saiji, Tomoaki Taguchi, Yoshinao Oda, Hiroshi Honda, Shoichi Ohga, Radiotherapy for Langerhans cell histiocytosis with paraplegia
A rare oncologic emergency case report in infancy and literature review, Brain and Development, 10.1016/j.braindev.2018.05.016, 40, 10, 952-955, 2018.11, Background: Langerhans cell histiocytosis (LCH) is a clonal disease with focal or disseminated lesions that may compress the surrounding tissues, including the spinal cord. Because few reports have described the spinal symptoms as the first manifestation of pediatric LCH, the long-term neurological outcomes remain unclear. Case report and literature review: We report a 21-month-old boy who presented with sudden-onset paraplegia. Imaging analyses revealed that osteolytic lesions and epidural tumors compressing the spinal cord at the T7-9 vertebrae. Twelve days after he developed leg weakness, emergency radiotherapy was started after a tumor biopsy. During the course of radiotherapy, paralysis steadily ameliorated. After we excluded infections and determined the pathological diagnosis of LCH, multi-drug chemotherapy was started. Apparent improvement in his complete paraplegia was observed after a total 15 Gy of radiotherapy and subsequent chemotherapy, leaving no neurological sequelae at 4 years of age. Through a literature search of studies published from 1980 to 2017, we found that children with LCH showed a generally favorable recovery from neurological dysfunction after the acute phase of spinal symptoms. Conclusion: This report underscores the utility of emergency radiotherapy for the neurological recovery of spinal LCH in infants. Our long-term observation further denotes the value of this treatment in terms of the intact survival with preserved motor functions and physical growth..
|90.||Hiroe Itami, Shigeo Hara, Masanori Matsumoto, Shin Imamura, Rie Kanai, Kei Nishiyama, masataka ishimura, Shoichi Ohga, Makiko Yoshida, Ryojiro Tanaka, Yoshiyuki Ogawa, Yujiro Asada, Yoko Sekita-Hatakeyama, Kinta Hatakeyama, Chiho Ohbayashi, Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome, Thrombosis Research, 10.1016/j.thromres.2018.08.020, 170, 148-155, 2018.10, Introduction: Upshaw-Schulman syndrome (USS) is a congenital form of thrombotic thrombocytopenic purpura (TTP) associated with loss-of-function mutations in the ADAMTS13 gene, possibly leading to aberrant complement activation and vascular injury. However, USS is extremely rare, and there have been no systematic studies correlating histopathological severity with local ADAMTS13 expression and complement activation. Materials and methods: Here, we compared histopathological features, ADAMTS13 immunoreactivity, and immunoreactivity of complement proteins C4d and C5b-9 among renal biopsy tissues from five USS cases, ten acquired TTP cases, and eleven controls. Results: Pathological analysis revealed chronic glomerular sclerotic changes in the majority of USS cases (4 of 5), with minor glomerular pathology in the remaining case. In two of these four severe cases, more than half of the glomerular segmental sclerosis area was localized in the perihilar region. The average number of ADAMTS13-positive cells per glomerulus was significantly lower in USS cases than controls (p < 0.05). Conversely, C4d staining was significantly more prevalent in the glomerular capillary walls of USS cases than controls (p < 0.05), while C5b-9 staining did not differ significantly among groups. Conclusions: These findings suggest that the severity of glomerular injury in USS is associated with deficient ADAMTS13 expression and local complement activation, particularly in vascular regions with higher endothelial shear stress. We suggest that C4d immunostaining provides evidence for complement-mediated glomerular damage in USS..|
|91.||Noriyuki Kaku, Kenji Ihara, Yuichiro Hirata, Kenji Yamada, Sooyoung Lee, Hikaru Kanemasa, Yoshitomo Motomura, Haruhisa Baba, Tamami Tanaka, Yasunari Sakai, Yoshihiko Maehara, Shoichi Ohga, Diagnostic potential of stored dried blood spots for inborn errors of metabolism
A metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency, Journal of Clinical Pathology, 10.1136/jclinpath-2017-204962, 71, 10, 885-889, 2018.10, Aim It is estimated that 1-5% of sudden infant death syndrome (SIDS) cases might be caused by undiagnosed inborn errors of metabolism (IEMs); however, the postmortem identification of IEMs remains difficult. This study aimed to evaluate the usefulness of dried blood spots (DBSs) stored after newborn screening tests as a metabolic autopsy to determine the causes of death in infants and children who died suddenly and unexpectedly. Methods Infants or toddlers who had suddenly died without a definite diagnosis between July 2008 and December 2012 at Kyushu University Hospital in Japan were enrolled in this study. Their Guthrie cards, which had been stored for several years at 4-8°C, were used for an acylcarnitine analysis by tandem mass spectrometry to identify inborn errors of metabolism. Results Fifteen infants and children who died at less than 2 years of age and for whom the cause of death was unknown were enrolled for the study. After correcting the C0 and C8 values assuming the hydrolysation of acylcarnitine in the stored DBSs, the corrected C8 value of one case just exceeded the cut-off level for medium-chain acyl-CoA dehydrogenase (MCAD) deficiency screening. Genetic and biochemical analyses confirmed this patient to have MCAD deficiency. Conclusion DBSs stored after newborn screening tests are a promising tool for metabolic autopsy. The appropriate compensation of acylcarnitine data and subsequent genetic and biochemical analyses are essential for the postmortem diagnosis of inborn errors of metabolism..
|92.||Hiroki Ono, Ryo Ohta, Yuri Kawasaki, Akira Niwa, Hidetoshi Takada, Tatsutoshi Nakahata, Shoichi Ohga, Megumu K. Saito, Lysosomal membrane permeabilization causes secretion of IL-1β in human vascular smooth muscle cells, Inflammation Research, 10.1007/s00011-018-1178-z, 67, 10, 879-889, 2018.10, Objective: IL-1β secretion by the inflammasome is strictly controlled and requires two sequential signals: a priming signal and an activating signal. Lysosomal membrane permeabilization (LMP) plays a critical role in the regulation of NLRP3 inflammasome, and generally acts as an activating signal. However, the role of LMP controlling NLRP3 inflammasome activation in human vascular smooth muscle cells (hVSMCs) is not well defined. Methods: LMP was induced in hVSMCs by Leu-Leu-O-methyl ester. Cathepsin B was inhibited by CA-074 Me. Cytokine release, mRNA, and protein were quantified by enzyme-linked immunosorbent assay, quantitative PCR, and Western blot, respectively. NF-κB activity was analyzed by immunostaining of the NF-κB p65 nuclear translocation and using the dual-luciferase reporter assay system. Results: LMP had both priming and activating roles, causing an upregulation of proIL-1β and NLRP3 and the secretion of mature IL-1β from unprimed hVSMCs. LMP activated the canonical NF-κB pathway. The priming effect of LMP was inhibited by CA-074 Me, indicating an upstream role of cathepsin B. Conclusions: These data support a novel role of LMP as a single stimulus for the secretion of IL-1β from hVSMCs, implying the possibility that hVSMCs are an important initiator of the sterile inflammatory response caused by lysosomal disintegration..|
|93.||Mitsuru Arima, Shouko Tsukamoto, Rumi Akiyama, Kei Nishiyama, Ri ichiro Kohno, Takashi Tachibana, Akira Hayashida, Miwa Murayama, Toshio Hisatomi, Kandai Nozu, Kazumoto Iijima, Shoichi Ohga, Kohei Sonoda, Ocular findings in a case of Pierson syndrome with a novel mutation in laminin ß2 gene, Journal of AAPOS, 10.1016/j.jaapos.2018.03.016, 22, 5, 401-403.e1, 2018.10, Pierson syndrome, an autosomal recessive disorder caused by a mutation in laminin ß2 (LAMB2) gene, is characterized by congenital nephrotic syndrome and various ocular abnormalities. The ocular findings in Pierson syndrome are not well understood, because the incidence of this syndrome is very rare. We report ocular findings in a 5-month-old boy with Pierson syndrome with a novel mutation in LAMB2. We performed a pupilloplasty for his microcoria. Ophthalmic examinations after surgery revealed that he had cataract, severe retinal degeneration, and high myopia. Optical coherence tomography showed the collapse of retinal layer structures and a marked decrease of choroidal thickness. Immunohistochemistry and electron microscopy examinations revealed abnormal iris differentiation and thinning or defect of basal membranes. These results suggest that the development of the iris, lens, retina, and choroid are affected in this type of mutation..|
|94.||A pediatric case with prostaglandin I2-associated thyrotoxicosis: Case report and the literature review..|
|95.||Diagnostic potential of stored dried blood spots for inborn errors of metabolism: a metabolic autopsy of medium-chain acyl-CoA dehydrogenase deficiency..|
|96.||Ono H, Ohta R, Kawasaki Y, Niwa A, Takada H, Nakahata T, Ohga S, Saito MK, Lysosomal membrane permeabilization causes secretion of IL-1β in human vascular smooth muscle cells., Inflammation research : official journal of the European Histamine Research Society ... [et al.], 10.1007/s00011-018-1178-z, 67, 10, 879-889, 2018.10.|
|97.||Tsutomu Toki, Kenichi Yoshida, Ru Nan Wang, Sou Nakamura, Takanobu Maekawa, Kumiko Goi, Megumi C. Katoh, Seiya Mizuno, Fumihiro Sugiyama, Rika Kanezaki, Tamayo Uechi, Yukari Nakajima, Yusuke Sato, Yusuke Okuno, Aiko Sato-Otsubo, Yusuke Shiozawa, Keisuke Kataoka, Yuichi Shiraishi, Masashi Sanada, Kenichi Chiba, Hiroko Tanaka, Kiminori Terui, Tomohiko Sato, Takuya Kamio, Hirotoshi Sakaguchi, Shoichi Ohga, Madoka Kuramitsu, Isao Hamaguchi, Akira Ohara, Hitoshi Kanno, Satoru Miyano, Seiji Kojima, Akira Ishiguro, Kanji Sugita, Naoya Kenmochi, Satoru Takahashi, Koji Eto, Seishi Ogawa, Etsuro Ito, De Novo Mutations Activating Germline TP53 in an Inherited Bone-Marrow-Failure Syndrome, American journal of human genetics, 10.1016/j.ajhg.2018.07.020, 103, 3, 440-447, 2018.09, Inherited bone-marrow-failure syndromes (IBMFSs) include heterogeneous genetic disorders characterized by bone-marrow failure, congenital anomalies, and an increased risk of malignancy. Many lines of evidence have suggested that p53 activation might be central to the pathogenesis of IBMFSs, including Diamond-Blackfan anemia (DBA) and dyskeratosis congenita (DC). However, the exact role of p53 activation in each clinical feature remains unknown. Here, we report unique de novo TP53 germline variants found in two individuals with an IBMFS accompanied by hypogammaglobulinemia, growth retardation, and microcephaly mimicking DBA and DC. TP53 is a tumor-suppressor gene most frequently mutated in human cancers, and occasional germline variants occur in Li-Fraumeni cancer-predisposition syndrome. Most of these mutations affect the core DNA-binding domain, leading to compromised transcriptional activities. In contrast, the variants found in the two individuals studied here caused the same truncation of the protein, resulting in the loss of 32 residues from the C-terminal domain (CTD). Unexpectedly, the p53 mutant had augmented transcriptional activities, an observation not previously described in humans. When we expressed this mutant in zebrafish and human-induced pluripotent stem cells, we observed impaired erythrocyte production. These findings together with close similarities to published knock-in mouse models of TP53 lacking the CTD demonstrate that the CTD-truncation mutations of TP53 cause IBMFS, providing important insights into the previously postulated connection between p53 and IBMFSs..|
|98.||Pin Fee Chong, Yasunari Sakai, Hiroyuki Torisu, Tamami Tanaka, Kenji Furuno, Yumi Mizuno, Shoichi Ohga, Toshiro Hara, Ryutaro Kira, Leucine-rich alpha-2 glycoprotein in the cerebrospinal fluid is a potential inflammatory biomarker for meningitis, Journal of the Neurological Sciences, 10.1016/j.jns.2018.07.006, 392, 51-55, 2018.09, Background: Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for inflammatory diseases. We evaluated the levels of LRG, interleukin (IL)-6, and tumor necrosis factor (TNF)-α in the cerebrospinal fluid (CSF) of children with meningitis. Methods: CSF samples from 10 patients with bacterial meningitis (BM) and 10 with aseptic meningitis (AM) were evaluated. Samples from 10 patients with febrile status (FS) were used as controls. LRG levels were measured using a two-site enzyme immunoassay. IL-6 and TNF-α levels were measured using a multiplex bead-based assay. CSF examination of patients with BM at the convalescent stage was also conducted. Results: LRG and TNF-α levels in patients with BM, and IL-6 levels in patients with BM and AM showed significant increase compared with those in FS. Patients with BM at the convalescent stage showed significantly diminished LRG and IL-6 levels. LRG and IL-6 levels in CSF were indicated to be effective predictors for BM (LRG, AUC = 0.91; IL-6, AUC = 0.85). Only LRG levels showed a significant difference between patients with BM and AM (AUC = 0.78, P = 0.034). Conclusions: LRG level could be a sensitive inflammatory biomarker for inflammatory diseases of the central nervous system, comparable with IL-6 level..|
|99.||K. Nogami, M. Taki, T. Matsushita, Shoichi Ohga, T. Oka, Y. Horikoshi, K. Amano, M. Shima, The Japanese Immune Tolerance Induction (J-ITI) study in haemophilia patients with inhibitor
Outcomes and successful predictors of ITI treatment, Haemophilia, 10.1111/hae.13531, 24, 5, e328-e337, 2018.09, Introduction: Immune tolerance induction (ITI) was the primary therapeutic approach to eradicate inhibitors in haemophilia patients. Several large ITI registries had been reported, but successful predictors of ITI outcome are still debated. No reports are available on large ITI studies in non-caucasian countries. Aim: We designed a retrospective cohort study of ITI in Japanese haemophilia patients with inhibitor. Methods: Retrospective data were collected from 155 haemophilia (H)A (140 severe-type) and 7 HB (7 severe-type) patients treated at 45 institutions. ITI outcome was centrally reviewed. We defined “success” as undetectable inhibitor after 2 consecutive measurements. Results: The ITI success rate was 71.2% for HA and 83.3% for HB. Cumulated success rates for HA achieving 50% and 75% were 0.7 and 2 years after treatment, respectively. Significant successful predictors in HA were low-responding inhibitors compared to high-responding inhibitors, shorter time to the start of ITI, and lower historical and treatment peak titres of inhibitor. Dose regimen (high dose; ≥90 IU/kg every day, low dose; ≤75 IU/kg, 3 d/wk) and the type of therapeutic product did not affect outcomes. The success rate of salvage ITI using von Willebrand factor-containing factor VIII was 50% (n = 6/12), and patient age at the start of salvage ITI was a significant predictor. The inhibitor recurred in 6 HA cases (3.9%). Conclusion: The results provided potentially important information for improving future success rates for ITI in inhibitor patients..
|100.||Nanishi E, Hoshina T, Sanefuji M, Kadoya R, Katsuhiko K, Arahata Y, Sato T, Hirayama Y, Hirai K, Yanai M, Nikaido K, Maeda A, Torisu H, Okada K, Sakai Y, Ohga S., A nationwide survey of pediatric-onset Japanese encephalitis in Japan, Clin Infect Dis, 10.1093/cid/ciy816., 2018.09, BACKGROUND: Japanese encephalitis (JE) is the leading cause of viral encephalitis with high mortality and morbidity in Asia. In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis. We aimed to determine the recent incidence of childhood-onset JE after the domestic change of vaccination policy in Japan, and to analyze the clinical features of affected children.
METHODS: A retrospective nationwide survey was conducted for pediatric patients with JE in Japan from 1995 to 2015. The national surveillance system was used to identify the pediatric patients with JE. Follow-up questionnaires were sent to analyze their clinical and neuroimaging profiles.
RESULTS: Among a total of 109 patients registered to the national surveillance, 10 (9%) were less than age 15 years. The annual incidence rate of childhood-onset JE was higher during 2005-15 than that during 1995-2004 (4.3 × 10-3 vs 1.1 × 10-3 per 100000, respectively; P = .04). Endemic regions overlapped with prefectures that farmed pigs harboring antibodies against JE virus with high prevalence. Detailed clinical data were collected from 9 patients. None of them died, but 5 of 9 patients (56%) had neurological sequelae after recovery. One patient who was partially vaccinated with 2 doses of JE vaccine fully recovered from a coma. The age of 3 years or less was associated with unfavorable neurological prognosis.
CONCLUSIONS: Our data provide evidence for the importance and prophylactic effect of the JE vaccine in young children in the endemic area..
|101.||A nationwide survey of pediatric-onset Japanese encephalitis in Japan..|
|102.||原 寿郎, Chemokine levels predict progressive liver disease in Down syndrome patients with transient abnormal myelopoiesis., Pediatr Neonatol, https://doi.org/10.1016/j.pedn, 2018.09.|
|103.||Complement activation associated with ADAMTS13 deficiency may contribute to the characteristic glomerular manifestations in Upshaw-Schulman syndrome..|
|104.||Tsutomu Toki, Kenichi Yoshida, RuNan Wang, Sou Nakamura, Takanobu Maekawa, Kumiko Goi, Megumi C Katoh, Seiya Mizuno, Fumihiro Sugiyama, Rika Kanezaki, Tamayo Uechi, Yukari Nakajima, Yusuke Sato, Yusuke Okuno, Aiko Sato-Otsubo, Yusuke Shiozawa, Keisuke Kataoka, Yuichi Shiraishi, Masashi Sanada, Kenichi Chiba, Hiroko Tanaka, Kiminori Terui, Tomohiko Sato, Takuya Kamio, Hirotoshi Sakaguchi, Shouichi Ohga, Madoka Kuramitsu, Isao Hamaguchi, Akira Ohara, Hitoshi Kanno, Satoru Miyano, Seiji Kojima, Akira Ishiguro, Kanji Sugita, Naoya Kenmochi, Satoru Takahashi, Koji Eto, Seishi Ogawa, Etsuro Ito, De Novo Mutations Activating Germline TP53 in an Inherited Bone-Marrow-Failure Syndrome., American journal of human genetics, 10.1016/j.ajhg.2018.07.020, 103, 3, 440-447, 2018.09, Inherited bone-marrow-failure syndromes (IBMFSs) include heterogeneous genetic disorders characterized by bone-marrow failure, congenital anomalies, and an increased risk of malignancy. Many lines of evidence have suggested that p53 activation might be central to the pathogenesis of IBMFSs, including Diamond-Blackfan anemia (DBA) and dyskeratosis congenita (DC). However, the exact role of p53 activation in each clinical feature remains unknown. Here, we report unique de novo TP53 germline variants found in two individuals with an IBMFS accompanied by hypogammaglobulinemia, growth retardation, and microcephaly mimicking DBA and DC. TP53 is a tumor-suppressor gene most frequently mutated in human cancers, and occasional germline variants occur in Li-Fraumeni cancer-predisposition syndrome. Most of these mutations affect the core DNA-binding domain, leading to compromised transcriptional activities. In contrast, the variants found in the two individuals studied here caused the same truncation of the protein, resulting in the loss of 32 residues from the C-terminal domain (CTD). Unexpectedly, the p53 mutant had augmented transcriptional activities, an observation not previously described in humans. When we expressed this mutant in zebrafish and human-induced pluripotent stem cells, we observed impaired erythrocyte production. These findings together with close similarities to published knock-in mouse models of TP53 lacking the CTD demonstrate that the CTD-truncation mutations of TP53 cause IBMFS, providing important insights into the previously postulated connection between p53 and IBMFSs..|
|105.||Pin Fee Chong, Yasunari Sakai, Hiroyuki Torisu, Tamami Tanaka, Kenji Furuno, Yumi Mizuno, Shouichi Ohga, Toshiro Hara, Ryutaro Kira, Leucine-rich alpha-2 glycoprotein in the cerebrospinal fluid is a potential inflammatory biomarker for meningitis., Journal of the neurological sciences, 10.1016/j.jns.2018.07.006, 392, 51-55, 2018.09, BACKGROUND: Leucine-rich alpha-2 glycoprotein (LRG) is a novel biomarker for inflammatory diseases. We evaluated the levels of LRG, interleukin (IL)-6, and tumor necrosis factor (TNF)-α in the cerebrospinal fluid (CSF) of children with meningitis. METHODS: CSF samples from 10 patients with bacterial meningitis (BM) and 10 with aseptic meningitis (AM) were evaluated. Samples from 10 patients with febrile status (FS) were used as controls. LRG levels were measured using a two-site enzyme immunoassay. IL-6 and TNF-α levels were measured using a multiplex bead-based assay. CSF examination of patients with BM at the convalescent stage was also conducted. RESULTS: LRG and TNF-α levels in patients with BM, and IL-6 levels in patients with BM and AM showed significant increase compared with those in FS. Patients with BM at the convalescent stage showed significantly diminished LRG and IL-6 levels. LRG and IL-6 levels in CSF were indicated to be effective predictors for BM (LRG, AUC = 0.91; IL-6, AUC = 0.85). Only LRG levels showed a significant difference between patients with BM and AM (AUC = 0.78, P = 0.034). CONCLUSIONS: LRG level could be a sensitive inflammatory biomarker for inflammatory diseases of the central nervous system, comparable with IL-6 level..|
|106.||Satoshi Akamine, Yoshito Ishizaki, Yasunari Sakai, Hiroyuki Torisu, Ryoko Fukai, Noriko Miyake, Kazuhiro Okubo, Hiroshi Koga, Masafumi Sanefuji, Ayumi Sakata, Masahiko Kimura, Seiji Yamaguchi, Osamu Sakamoto, Toshiro Hara, Hirotomo Saitsu, Naomichi Matsumoto, Shoichi Ohga, A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia, European Journal of Medical Genetics, 10.1016/j.ejmg.2018.03.003, 61, 8, 451-454, 2018.08, Mutations in the X-linked gene CDKL5 cause early-onset epileptic encephalopathy and severe developmental delay. Because this disorder predominantly affects females, the full clinical spectrum of male patients remains elusive. We herein report a 16-year-old boy, who suffered from intractable seizures 20 days after birth. Serial electroencephalograms detected recurrent focal epileptiform discharges from age 4 months, which evolved to hypsarrhythmia later in infancy. Mass-spectrometric analyses revealed increase in urinary excretion of methylmalonic acid without perturbed concentrations of propionic acid, homocystein and methionine. Whole-exome sequencing identified a de novo, truncating mutation in CDKL5 (NM_003159.2:c.419dupA, p.Asn140Lysfs*8). Targeted sequencing excluded concomitant mutations in methylmalonic academia-associated genes. No methylmalonic acidemia has been reported in children with CDKL5 disorder. Extensive analyses on organic acid metabolism for males with CDKL5 mutations will gain more insight into their biochemical profiles in infancy..|
|107.||Motoshi Sonoda, masataka ishimura, Yuko Shono, Eiko Terashi, Katsuhide Eguchi, Yasunari Sakai, Hidetoshi Takada, Asahito Hama, Hitoshi Kanno, Tsutomu Toki, Etsuro Ito, Shoichi Ohga, Atypical erythroblastosis in a patient with Diamond–Blackfan anemia who developed del(20q) myelodysplasia, International journal of hematology, 10.1007/s12185-018-2424-4, 108, 2, 228-231, 2018.08, Diamond–Blackfan anemia (DBA) is a congenital red cell aplasia arising from ribosomal protein (RP) defects. Affected patients present with neonatal anemia, occasional dysmorphism, and cancer predisposition. An anemic newborn was diagnosed with DBA due to RPL5 mutation (c.473_474del, p.K158SfsX26). Refractory anemia required regular transfusions and iron chelation therapy. Pancytopenia occurred at age 16 years. Bone-marrow studies showed myelodysplasia, erythroblastosis, and clonal evolution of del(20)(q11.2q13.3). Severe anemia required transfusions. Del(20q), including the L3MBTL1 gene, is reported to be relevant to the hematological phenotype of Shwachman–Diamond syndrome. A combined defect of RPL5 and L3MBTL1 may contribute to the aberrant erythropoiesis in the present case..|
|108.||Motoshi Sonoda, masataka ishimura, Yuko Shono, Eiko Terashi, Katsuhide Eguchi, Yasunari Sakai, Hidetoshi Takada, Asahito Hama, Hitoshi Kanno, Tsutomu Toki, Etsuro Ito, Shoichi Ohga, Correction to
Atypical erythroblastosis in a patient with Diamond–Blackfan anemia who developed del(20q) myelodysplasia (International Journal of Hematology, (2018), 108, 2, (228-231), 10.1007/s12185-018-2424-4), International journal of hematology, 10.1007/s12185-018-2493-4, 108, 2, 2018.08, The corresponding author should be ‘‘Masataka Ishimura’’, and not ‘‘Motoshi Sonoda’’ as given in the original publication of the article..
|109.||Kenichiro Yamamura, Shoichi Ohga, Letter to ‘Pregnancy and delivery outcomes from patients with repaired anomalous origin of the left coronary artery from the pulmonary artery’, Journal of Obstetrics and Gynaecology Research, 10.1111/jog.13673, 44, 8, 2018.08.|
|110.||Tomohiro Okuda, Nobuhiro Hata, Satoshi Suzuki, Koji Yoshimoto, Koichi Arimura, Takeo Amemiya, Yojiro Akagi, Daisuke Kuga, Utako Oba, Yuhki Koga, Shoichi Ohga, Toru Iwaki, Koji Iihara, Pediatric ganglioglioma with an H3 K27M mutation arising from the cervical spinal cord, Neuropathology, 10.1111/neup.12471, 38, 4, 422-427, 2018.08, The 2016 edition of the World Health Organization Classification of Tumors of the Central Nervous System introduced “diffuse midline glioma H3 K27M mutant” as a new diagnostic entity. These tumors predominately affect pediatric patients and arise from midline structures such as the brainstem, thalamus and spinal cord. Here, we report a rare patient with spinal ganglioglioma carrying an H3 K27M mutation. A 10-year-old boy presented with an intramedullary tumor in the cervical spinal cord. The lesion was partially removed and histologically diagnosed as ganglioglioma. After the remnant tumor grew within 3 months after surgery, the patient underwent radiotherapy. Genetic analyses revealed an H3F3A K27M mutation but no other genetic alterations such as IDH and BRAF mutations. This case may point to pathological heterogeneity in gliomas with H3 K27M mutations..|
|111.||Vlad Tocan, Kazuhiro Okubo, Kanako Higashi, Naoko Toda, Kanako Kojima-Ishii, Kei Nishiyama, masataka ishimura, Hidetoshi Takada, Osamu Sakamoto, Fusako Sasaki, Kazuko Yoshimura, Shinichi Hirose, Shoichi Ohga, Reappraising newborn screening for cobalamin C disorder, Pediatrics and Neonatology, 10.1016/j.pedneo.2017.11.002, 59, 4, 415-417, 2018.08.|
|112.||Koichiro Yoshimaru, Toshiharu Matsuura, Yoshiaki Takahashi, Yusuke Yanagi, Hazumu Nagata, Shoichi Ohga, Tomoaki Taguchi, The efficacy of serum brain natriuretic peptide for the early detection of portopulmonary hypertension in biliary atresia patients before liver transplantation, Pediatric Transplantation, 10.1111/petr.13203, 22, 5, 2018.08, Severe portopulmonary hypertension (POPH) is a contraindication for liver transplantation (LT) because of the high risk of postoperative heart failure. The early detection of POPH is important for patients with biliary atresia (BA). Brain natriuretic peptide (BNP) is known to be correlated with liver fibrosis in patients with liver cirrhosis. The aim of this study was to elucidate the efficacy of BNP measurement for the follow-up of patients with BA. Thirty-two patients with BA were identified from September 2011 to December 2016. As indices of liver fibrosis/cirrhosis, APRI (P <.0001), FIB-4 (P <.0001), Child-Pugh score (P <.0001), IV collagen (P =.0005), and hyaluronic acid (P =.0291) had high or moderate correlations with BNP. Patients with splenomegaly, esophageal varices, liver fibrosis, and collateral veins had significantly higher BNP levels than those without. Patients diagnosed with POPH had significantly higher BNP levels in comparison with those patients without (P =.0068). In contrast, PELD/MELD scores showed an almost negligible correlation with the BNP level. LT was successful in 3 asymptomatic BA patients with POPH who had high BNP levels despite the low PELD/MELD scores. In conclusion, routine serum BNP surveillance can be easy to predict asymptomatic POPH. This may help to identify POPH before it reaches a stage that would contraindicate LT..|
|113.||Atypical erythroblastosis in a patient with Diamond-Blackfan anemia who developed del(20q) myelodysplasia..|
|114.||Correction to: Atypical erythroblastosis in a patient with Diamond-Blackfan anemia who developed del(20q) myelodysplasia..|
|115.||Ocular findings in a case of Pierson syndrome with a novel mutation in laminin ß2 gene..|
|116.||Sayaka Okuzono, masataka ishimura, Shunsuke Kanno, Motoshi Sonoda, Noriyuki Kaku, Yoshitomo Motomura, Hisanori Nishio, Utako Oba, Masuo Hanada, Jun-Ichi Fukushi, Michiyo Urata, Dongchon Kang, Hidetoshi Takada, Shoichi Ohga, Streptococcus pyogenes-purpura fulminans as an invasive form of group A streptococcal infection, Annals of Clinical Microbiology and Antimicrobials, 10.1186/s12941-018-0282-9, 17, 1, 2018.07, Background: Streptococcus pyogenes is an uncommon pathogen of purpura fulminans, and the pathogenesis of S. pyogenes-purpura fulminans remains unclear because of paucity of cases. We reported a pediatric case of S. pyogenes-purpura fulminans with literature review of the disease. Case presentation: A 3-year-old boy showed limping, lethargy and acral gangrene within 24 h. A diagnosis of S. pyogenes-purpura fulminans was made for bacterial isolation from throat and peripheral blood. Intensive therapy led to a survival with amputation of the left distal metatarsal bone, and normal development. The isolated M12 carried no mutation of csrS/R or rgg. Thrombophilia or immunodeficiency was excluded. Discussion: Twelve-reported cases (9 pediatric and 3 elderly) of S. pyogenes-purpura fulminans started with shock and coagulopathy. Five patients age < 8 years had no underlying disease and survived. One youngest and two immunocompromised patients died. Conclusion:Streptococcus pyogenes-acute infectious purpura fulminans is a distinctive rare form of aggressive GAS infections..|
|117.||Hideto Teranishi, Yuhki Koga, Kentaro Nakashima, Eiji Morihana, Kanako Ishii, Yasunari Sakai, Tomoaki Taguchi, Yoshinao Oda, Noriko Miyake, Naomichi Matsumoto, Shoichi Ohga, Cancer management in kabuki syndrome
The first case of wilms tumor and a literature review, Journal of Pediatric Hematology/Oncology, 10.1097/MPH.0000000000001111, 40, 5, 391-394, 2018.07, A 3-year-old Japanese girl treated for hypoplastic left heart syndrome and Dandy-Walker syndrome was diagnosed with Kabuki syndrome (KS) with a mutation of KMT2D; c.13285C>T:p.Q4429∗. Concurrently, macrohematuria portended the diagnosis of Wilms tumor. Postoperative chemotherapy has achieved complete remission despite a prolonged and reduced regimen due to liver dysfunction and convulsions. Cancer predisposition has been suggested for KS due to oncogenic mutations in KMT2D or KDM6A. The first case of nephroblastoma exemplified the treatability of malignancies in KS patients, as shown in the 9 cases reviewed. Active screening and intervention are recommended for the cure of malignancy in KS children..
|118.||Katsuhide Eguchi, masataka ishimura, Motoshi Sonoda, Hiroki Ono, Akira Shiraishi, Shunsuke Kanno, Yuhki Koga, Hidetoshi Takada, Shoichi Ohga, Nontuberculous mycobacteria-associated hemophagocytic lymphohistiocytosis in MonoMAC syndrome, Pediatric Blood and Cancer, 10.1002/pbc.27017, 65, 7, 2018.07.|
|119.||Yuko Shono, Noriyuki Kaku, Masafumi Sanefuji, Michiko Torio, Soichi Mizuguchi, Yoshitomo Motomura, Mamoru Muraoka, Sooyoung Lee, Haruhisa Baba, Yuri Sonoda, Yoshito Ishizaki, Momoko Sasazuki, Yasunari Sakai, Yoshihiko Maehara, Shoichi Ohga, Predictive indicators for the development of epilepsy after acute encephalopathy with biphasic seizures and late reduced diffusion, Epilepsy Research, 10.1016/j.eplepsyres.2018.04.006, 143, 70-74, 2018.07, Acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) is a newly defined clinicoradiologic syndrome characterized by biphasic seizures and altered consciousness followed by restricted diffusion in the white matter on magnetic resonance imaging in acute phase. Intractable epilepsy commonly occurs as the late complication. This study aimed to search predisposing factors to the development of epilepsy after AESD. Consecutively treated 22 patients with AESD in our institution from 2006 to 2016 were grouped into those with post-encephalopathic epilepsy (PEE, n = 10) or without PEE (n = 12). There was no difference between two groups in age at the onset of AESD, duration of the initial seizures, or the follow-up periods after discharge. PEE group patients more frequently showed coma or involuntary movements during the course of AESD than non-PEE group patients (36% vs. 8%, p = 0.008). The quantitative analysis of apparent diffusion coefficient (ADC) map revealed that PEE group showed broader areas with reduced diffusion in the posterior lobes at the onsets of AESD than non-PEE group (0.113 vs. 0.013, p = 0.035). On the other hand, the atrophy on day 30-ADC map did not correlate with the development or control of epilepsy. These results suggest that the clinical severity and ADC profiles in acute phase, rather than the brain atrophy in convalescent phase, may predict the development of post-AESD epilepsy..|
|120.||Cancer Management in Kabuki Syndrome: The First Case of Wilms Tumor and a Literature Review..|
|121.||Streptococcus pyogenes-purpura fulminans as an invasive form of group A streptococcal infection..|
|122.||Yuko Noda, Yuhki Koga, Momoe Ohta, Mami Miyazono, Yoko Wakasugi, Yukie Funakoshi, Yuki Urabe, Miho Kifune, Tamaki Ueda, Utako Oba, Kentaro Nakashima, Ryota Sozaki, Yoshiaki Kinoshita, Tomoaki Taguchi, Shoichi Ohga, Survey of anticancer drug exposure to attendant families in pediatric medical centers, Japanese Journal of Cancer and Chemotherapy, 45, 6, 945-948, 2018.06, The occupational exposure to hazardous drugs (HD) has already been investigated; however, the actual exposure of the attendant family members of patients with childhood cancer has remained unknown. Here, we analyzed cyclophosphamide (CPM) exposure in attendant family members and the environment after the administration of CPM to patients with pediatric cancer. CPM of 320 (8.39-1, 510) ng from infant-families and 0 (0-58.4) ng from adolescent-families were detected (p= 0.01). The exposure of infant-families was significantly greater than those of adolescent-families. In addition, CPM were detected in the hot water after bathing the infant, underwear, and sheets. We elucidated that the exposures take place through body fluid and excretions of the children. In the field of childhood cancer, HD exposure measures should be taken according to the age of the child to minimize health damage to medical personnel, family members, and other children who share the room. Nurses are recommended to educate the patients and their family members about preventing exposure to HD in pediatric medical centers..|
|123.||[Survey of Anticancer Drug Exposure to Attendant Families in Pediatric Medical Centers]..|
|124.||Kiyoshi Uike, Hazumu Nagata, Yuichiro Hirata, Kenichiro Yamamura, Eiko Terashi, Toshiharu Matsuura, Eiji Morihana, Kazuhiro Okubo, Kanako Ishii, Yasunari Sakai, Tomoaki Taguchi, Shoichi Ohga, Effective shunt closure for pulmonary hypertension and liver dysfunction in congenital portosystemic venous shunt, Pediatric Pulmonology, 10.1002/ppul.23944, 53, 4, 505-511, 2018.04, Objective: Congenital portosystemic venous shunt (CPSVS) is a rare vascular malformation with a high risk of mortality from pulmonary arterial hypertension (PAH), but the treatment outcome of CPSVS closure remains elusive. Our aim was to investigate the clinical features and establish the optimal management of CPSVS with or without PAH. Methods: Twenty-four patients with CPSVS treated in Kyushu University Hospital between 1990 and 2015 were enrolled in this study. The patients were divided into a PAH group (n = 9) and a non-PAH group (n = 15). Clinical characteristics and outcomes were evaluated. Results: The first manifestation of CPSVS at diagnosis (28.5 [1-216] months) was hypergalactosemia in 13 (54%) or PAH in six (25%) patients. PAH was the cause of all three deaths. The PAH group had higher levels of serum total bile acid, manganese, and total bilirubin, along with higher pulmonary vascular resistance index (PVRI) than the non-PAH group (7.2 [5.1-38.1] vs 1.2 [0.5-3.3] unit/m 2 , P < 0.001). Five of nine PAH patients underwent CPSVS closure at a median of 38 months (range 21-118) after PAH diagnosis. Pulmonary artery pressure improved after CPSVS closure with PAH-specific therapy, but normal range was not achieved. CPSVS closure improved the hepatic synthetic function of four PAH patients. Eight of 15 non-PAH patients who received CPSVS closure did not develop PAH for a median of 34.5 months (range 6-164) after the procedure. Conclusions: CPSVS closure with PAH-specific therapy successfully controlled PAH. Early CPSVS closure may prevent the occurrence and progression of PAH with CPSVS...|
|125.||Saki Hirofuji, Yuta Hirofuji, Hiroki Kato, Keiji Masuda, Haruyoshi Yamaza, Hiroshi Sato, Fumiko Takayama, Michiko Torio, Yasunari Sakai, Shoichi Ohga, Tomoaki Taguchi, Kazuaki Nonaka, Mitochondrial dysfunction in dopaminergic neurons differentiated from exfoliated deciduous tooth-derived pulp stem cells of a child with Rett syndrome, Biochemical and Biophysical Research Communications, 10.1016/j.bbrc.2018.03.077, 498, 4, 898-904, 2018.04, Rett syndrome is an X-linked neurodevelopmental disorder associated with psychomotor impairments, autonomic dysfunctions and autism. Patients with Rett syndrome have loss-of-function mutations in MECP2, the gene encoding methyl-CpG-binding protein 2 (MeCP2). Abnormal biogenic amine signaling and mitochondrial function have been found in patients with Rett syndrome; however, few studies have analyzed the association between these factors. This study investigated the functional relationships between mitochondria and the neuronal differentiation of the MeCP2-deficient stem cells from the exfoliated deciduous teeth of a child with Rett syndrome. An enrolled subject in this study was a 5-year-old girl carrying a large deletion that included the methyl-CpG-binding domain, transcriptional repression domain, and nuclear localization signal of MECP2. Using the single-cell isolation technique, we found that the two populations of MeCP2-expressing and MeCP2-deficient stem cells kept their MECP2 expression profiles throughout the stages of cell proliferation and neuronal differentiation in vitro. Neurite outgrowth and branching were attenuated in MeCP2-deficient dopaminergic neurons. MeCP2-deficient cells showed reduced mitochondrial membrane potential, ATP production, restricted mitochondrial distribution in neurites, and lower expression of a central mitochondrial fission factor, dynamin-related protein 1 than MeCP2-expressing cells. These data indicated that MeCP2-deficiency dysregulates the expression of mitochondrial factors required for the maturation of dopaminergic neurons. This study also provides insight into the pathogenic mechanism underlying dysfunction of the intracerebral dopaminergic signaling pathway in Rett syndrome..|
|126.||Eiji Morihana, Kenichiro Yamamura, Yuichiro Sugitani, Hideaki Kado, Yasushi Takahata, Toshihide Nakano, Yasutaka Nakashima, Naoki Fusazaki, Shoichi Ohga, Prolonged PR Interval at Birth Predicting the High Occurrence of Fatal Atrioventricular Block in Hypoplastic Left Heart Syndrome, Pediatric Cardiology, 10.1007/s00246-018-1815-x, 39, 4, 749-756, 2018.04, Infants with hypoplastic left heart syndrome (HLHS) are at high mortality especially when they are associated with bradyarrhythmias. However, the risk factor of developing high-grade atrioventricular block (HAVB) is still unclear. Seventy-three patients with HLHS in our institutions from 2002 to 2011 were enrolled. The survival rate was assessed by the anatomical types, treatments, occurrence of HAVB, severe tricuspid regurgitation (TR), and restrictive atrial septal defect (ASD) along with electrocardiogram findings at birth. There were 23 (32%) cardiogenic and 7 (10%) non-cardiogenic deaths. The occurrence rate of HAVB but not severe TR or restrictive ASD was higher in 30 deceased patients than in 43 survived patients [7 (23%) vs. 1 (2.3%), p = 0.0038]. The overall mortality rate was higher in patients with HAVB than in those without it (p = 0.0002). Of 7 deceased patients with HAVB, 6 HAVB occurred within 10 days post-surgery, and 3 HAVB led to the early death. The mortality rate of patients with prolonged PR (≥ 0.15 s) but not wide QRS (> 0.08 s) or prolonged QTc (> 0.43 s) at birth was higher than each without it (p = 0.0106). Multivariate analysis indicated that prolonged PR but no other variables was independently associated with the mortality (hazard ratio: 2.948, p = 0.0104). Prolonged PR at birth in HLHS infants predicts the development of fatal HAVB..|
|127.||Fever and Skin Involvement at Diagnosis Predicting the Intractable Langerhans Cell Histiocytosis: 40 Case-Series in a Single Center..|
|128.||Mitochondrial dysfunction in dopaminergic neurons differentiated from exfoliated deciduous tooth-derived pulp stem cells of a child with Rett syndrome.|
|129.||A male case with CDKL5-associated encephalopathy manifesting transient methylmalonic acidemia..|
|130.||Early-onset epileptic encephalopathy and severe developmental delay in an association with de novo double mutations in NF1 and MAGEL2..|
|131.||Yuichi Yamada, Izumi Kinoshita, Kohashi Kenichi, Hidetaka Yamamoto, Takeshi Iwasaki, Hiroshi Otsuka, Masato Yoshimoto, Shin Ishihara, Yu Toda, Yuki Kuma, Nokitaka Setsu, Yuki Koga, Yumi Honda, Takeshi Inoue, Hiroyuki Yanai, Kyoko Yamashita, Ichiro Ito, Mitsuru Takahashi, Shouichi Ohga, Masutaka Furue, Yasuharu Nakashima, Yoshinao Oda, Histopathological and genetic review of phosphaturic mesenchymal tumours, mixed connective tissue variant., Histopathology, 10.1111/his.13377, 72, 3, 460-471, 2018.02, AIMS: Phosphaturic mesenchymal tumour, mixed connective tissue variant (PMT-MCT), is a tumour of uncertain differentiation, characterised by 'smudgy/grungy' calcification and vitamin D-resistant phosphaturic osteomalacia. Fibroblast growth factor (FGF)23 is recognised as a reliable marker of PMT-MCT, but quantitative evaluation has never been performed. We reviewed cases of tumour-associated osteomalacia or histologically definitive PMT-MCT without osteomalacia using histological, immunohistochemical and genetic methods and evaluated the diagnostic significance of these findings. METHODS AND RESULTS: A total of 19 tumours from 14 cases diagnosed previously as PMT-MCT were retrieved, on which immunohistochemical staining, reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in-situ hybridisation (FISH) analysis were performed. Histologically, fibrous capsule, calcification and giant cell reaction tended to be observed in soft-tissue PMT-MCT, while PMT-MCT of bone and multiple PMT-MCT showed an infiltrative growth pattern. The immunohistochemical results were as follows: the tumour cells were positive for FGF23 (nine of 12, 75%), FGFR1 (11 of 11, 100%), CD56 (12 of 14, 85.7%) and E26 oncogene homologue (ERG) (5 of 13, 38.4%). The sole malignant tumour was positive for p53. FGF23 mRNA was detected in seven of 14 formalin-fixed paraffin-embedded (FFPE) specimens and all five frozen specimens by RT-PCR. The level of FGF23 mRNA, which was determined by real-time PCR, varied among the phosphaturic cases. Two of 17 tumours were positive for FGFR1 gene rearrangement. CONCLUSIONS: It was considered that PMT-MCT is a histopathological entity with or without phosphaturia, with varying levels of FGF23 mRNA, and with or without fibronectin 1 (FN1)-FGFR1 fusion gene. The authors propose that the histology of PMT-MCT differs depending on its location, such as bone or soft tissue, which could complicate the differential diagnosis..|
|132.||Thrombotic microangiopathy in a very young infant with mitral valvuloplasty..|
|133.||Makoto Mizutani, Shunji Hasegawa, Takeshi Matsushige, Naoki Ohta, Setsuaki Kittaka, Madoka Hoshide, Takeshi Kusuda, Kazumasa Takahashi, Kiyoshi Ichihara, Shouichi Ohga, Distinctive inflammatory profile between acute focal bacterial nephritis and acute pyelonephritis in children, CYTOKINE, 10.1016/j.cyto.2017.06.012, 99, 24-29, 2017.11, Background: Acute focal bacterial nephritis (AFBN) is a severe form of upper urinary tract infection (UTI) with neurological manifestations and focal renal mass lesions on computed tomography (CT). Prolonged antibiotic therapy may improve the renal outcome, but the early differential diagnosis of AFBN from acute pyelonephritis (APN) is challenging. We searched for effective biomarkers of AFBN based on the pathophysiology of upper UTIs.
Methods: Of 52 upper UTI cases treated at Yamaguchi University between 2009 and 2016, 38 pediatric patients with AFBN (n = 17) or APN (n = 21) who underwent ultrasonography and/or CT were enrolled. The clinical data and serum cytokine concentrations were analyzed to differentiate AFBN from APN.
Results: AFBN patients tended to be older, and have a higher body temperature, longer febrile period, more frequent neurological symptoms, higher immature neutrophil count, lower lymphocyte count, higher procalcitonin and urine beta(2)-microglobulin levels. AFBN patients showed higher serum levels of IFN-gamma, IL-6, IL-10 and soluble TNF-receptor 1 (sTNFR1) (all p < 0.05). Although the cytokine levels were variably correlated among each other, multiple logistic regression analysis revealed that combination of IFN-gamma and IL-6 levels were most relevant for distinguishing AFBN from APN. The discriminant power of the logistic equation was 0.86 in terms of the area under the curve by the ROC analysis.
Conclusions: Circulating 4 out of 7 cytokines in AFBN patients were at higher levels compared with those in APN patients. IFN-gamma and IL-6 levels might most effectively distinguish AFBN from APN..
|134.||Hirosuke Inoue, Masayuki Ochiai, Kazuaki Yasuoka, Koichi Tanaka, Hiroaki Kurata, Junko Fujiyoshi, Yuki Matsushita, Shutaro Suga, Kazuaki Nonaka, Tomoaki Taguchi, Kiyoko Kato, Shouichi Ohga, Early Mortality and Morbidity in Infants with Birth Weight of 500 Grams or Less in Japan, JOURNAL OF PEDIATRICS, 10.1016/j.jpeds.2017.05.017, 190, 112-+, 2017.11, Objective To assess the short-term prognosis of Japanese infants with a birth weight (BW) of <= 500 g.
Study design Demographic and clinical data were reviewed for 1473 live born infants with a BW <= 500 g at gestational age >= 22 weeks who were treated in the 204 affiliated hospitals of the Neonatal Research Network of Japan between 2003 and 2012.
Results Survival to hospital discharge occurred in 811 of 1473 infants (55%; 95% CI 53%-58%). The survival rates of BW = 300 g, 301-400 g, and 401-500 g were 18% (95% CI 10%-31%), 41% (95% CI 36%-47%), and 60% (95% CI 57%-63%), respectively. In a multivariable Cox proportional hazards analysis, antenatal corticosteroid use (adjusted hazard ratio: 0.68; 95% CI 0.58-0.81; P < .01), cesarean delivery (0.69; 95% CI 0.56-0.85; P < .01), advanced gestational age per week (0.94; 95% CI 0.89-0.99; P = .02), BW per 100-g increase (0.55; 95% CI 0.49-0.64; P < .01), Apgar score >= 4 at 5 minutes (0.51; 95% CI 0.43-0.61; P <.01), and no major congenital abnormalities (0.38; 95% CI 0.29-0.51; P <.01) were associated with survival to discharge. Despite the improved survival rate over the 10-year study period (from 40% in 2003 [95% CI 30%-51%] to 68% in 2012 [95% CI 61%-75%]), at least 1 severe morbidity was present in 81%-89% of the survivors.
Conclusions Improvements in perinatal-neonatal medicine have improved the survival, but not the rate of major morbidities, of infants with a BW <= 500 g in Japan..
|135.||K. Murata, Y. Motomura, T. Tanaka, S. Kanno, T. Yano, M. Onimaru, A. Shimoyama, H. Nishio, Y. Sakai, M. Oh-Hora, H. Hara, K. Fukase, H. Takada, S. Masuda, S. Ohga, S. Yamasaki, T. Hara, Calcineurin inhibitors exacerbate coronary arteritis via the MyD88 signalling pathway in a murine model of Kawasaki disease, CLINICAL AND EXPERIMENTAL IMMUNOLOGY, 10.1111/cei.13002, 190, 1, 54-67, 2017.10, Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)(-/-) and myeloid differentiation primary response gene 88 (MyD88)(-/-) mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9(-/-) mice but not in MyD88(-/-) mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD..|
|136.||Noriaki Sagata, Takahiro A. Kato, Shin-ichi Kano, Masahiro Ohgidani, Norihiro Shimokawa, Mina Sato-Kasai, Kohei Hayakawa, Nobuki Kuwano, Ashley M. Wilson, Koko Ishizuka, Shiori Kato, Takeshi Nakahara, Makiko Nakahara-Kido, Daiki Setoyama, Yasunari Sakai, Shouichi Ohga, Masutaka Furue, Akira Sawa, Shigenobu Kanba, Dysregulated gene expressions of MEX3D, FOS and BCL2 in human induced-neuronal (iN) cells from NF1 patients: a pilot study, SCIENTIFIC REPORTS, 10.1038/s41598-017-14440-7, 7, 1, 13905, 2017.10, Direct conversion technique to produce induced-neuronal (iN) cells from human fibroblasts within 2 weeks is expected to discover unknown neuronal phenotypes of neuropsychiatric disorders. Here, we present unique gene expression profiles in iN cells from patients with neurofibromatosis type 1 (NF1), a single-gene multifaceted disorder with comparatively high co-occurrence of autism spectrum disorder (ASD). Microarray-based transcriptomic analysis on iN cells from male healthy controls and male NF1 patients (NF1-iN cells) revealed that 149 genes expressions were significantly different (110 upregulated and 39 downregulated). We validated that mRNA of MEX3D (mex-3 RNA binding family member D) was lower in NF1-iN cells by real-time PCR with 12 sex-mixed samples. In NF1-iN cells on day 14, higher expression of FOS mRNA was observed with lower expression of MEX3D mRNA. Interestingly, BCL2 mRNA was higher in NF1-iN cells on day 5 (early-period) but not on day 14. Our data suggest that aberrant molecular signals due to NF1 mutations may disturb gene expressions, a subset of which defines continuum of the neuronal phenotypes of NF1 with ASD. Further translational studies using induced pluripotent stem (iPS) cell-derived neuronal cells are needed to validate our preliminary findings especially confirming meanings of analysis using early-period iN cells..|
|137.||Yui Takada, Yasunari Sakai, Yuki Matsushita, Kazuhiro Ohkubo, Yuhki Koga, Satoshi Akamine, Michiko Torio, Yoshito Ishizaki, Masafumi Sanefuji, Hiroyuki Torisu, Chad A. Shaw, Masayo Kagami, Toshiro Hara, Shouichi Ohga, Sustained endocrine profiles of a girl with WAGR syndrome, BMC MEDICAL GENETICS, 10.1186/s12881-017-0477-5, 18, 1, 117-117, 2017.10, Background: Wilms tumor, aniridia, genitourinary anomalies and mental retardation (WAGR) syndrome is a rare genetic disorder caused by heterozygous deletions of WT1 and PAX6 at chromosome 11p13. Deletion of BDNF is known eto be associated with hyperphagia and obesity in both humans and animal models; however, neuroendocrine and epigenetic profiles of individuals with WAGR syndrome remain to be determined.
Case presentation: We report a 5-year-old girl with the typical phenotype of WAGR syndrome. She showed profound delays in physical growth, motor and cognitive development without signs of obesity. Array comparative genome hybridization (CGH) revealed that she carried a 14.4 Mb deletion at 11p14.3p12, encompassing the WT1, PAX6 and BDNF genes. She experienced recurrent hypoglycemic episodes at 5 years of age. Insulin tolerance and hormonal loading tests showed normal hypothalamic responses to the hypoglycemic condition and other stimulations. Methylation analysis for freshly prepared DNA from peripheral lymphocytes using the pyro-sequencing-based system showed normal patterns of methylation at known imprinting control regions.
Conclusions: Children with WAGR syndrome may manifest profound delay in postnatal growth through unknown mechanisms. Epigenetic factors and growth-associated genes in WAGR syndrome remain to be characterized..
|138.||Pulmonary inflammation and cytokine dynamics of bronchoalveolar lavage fluid from a mouse model of bronchial asthma during A(H1N1)pdm09 influenza infection..|
|139.||Utako Oba, Hiroshi Yamada, So-ichi Suenobu, Yusuke Nakamura, Akiko Ito, Yutaka Hatano, Nobuyoshi Itonaga, Kouichi Ohshima, Yuhki Koga, Shouichi Ohga, Kenji Ihara, Toxic epidermal necrolysis in a child 6 months post-hematopoietic stem cell transplantation, PEDIATRIC TRANSPLANTATION, 10.1111/petr.12931, 21, 5, 2017.08, TEN is a rare and critical disease mostly caused by drugs. It is mediated by activated CD8+ T cells that cause keratinocyte apoptosis with the assistance of cytokines/chemokines. We herein report a pediatric case of TEN after allogeneic HSCT with precursor B-cell acute lymphoblastic leukemia (pre-B-ALL) in second complete remission. Although we did not evaluate the T-cell subpopulation in blood or skin lesion of the patient, an imbalanced immune reconstitution after HSCT might additively contribute to the development of TEN..|
|140.||Yuko Ichimiya, Noriyuki Kaku, Yasunari Sakai, Fumiya Yamashita, Wakato Matsuoka, Mamoru Muraoka, Satoshi Akamine, Soiai Mizuguchi, Michiko Torio, Yoshitomo Motomura, Yuichiro Hirata, Yoshito Ishizaki, Masafumi Sanefuji, Hiroyuki Torisu, Hidetoshi Takada, Yoshihiko Maehara, Shouichi Ohga, Transient dysautonomia in an acute phase of encephalopathy with biphasic seizures and late reduced diffusion, BRAIN & DEVELOPMENT, 10.1016/j.braindev.2017.03.023, 39, 7, 621-624, 2017.08, Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48 h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3 days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD. (C) 2017 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved..|
|141.||Shouichi Ohga, The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene, PEDIATRIC BLOOD & CANCER, 10.1002/pbc.26404, 64, 7, 2017.07, Protein C異常症の遺伝子型と表現型の解析から、両アレル変異の発症例を見いだした。.|
|142.||Akihiro Hoshino, Satoshi Okada, Kenichi Yoshida, Naonori Nishida, Yusuke Okuno, Hiroo Ueno, Motoi Yamashita, Tsubasa Okano, Miyuki Tsumura, Shiho Nishimura, Sonoko Sakata, Masao Kobayashi, Haruna Nakamura, Junji Kamizono, Kanako Mitsui-Sekinaka, Takuya Ichimura, Shouichi Ohga, Yozo Nakazawa, Masatoshi Takagi, Kohsuke Imai, Yuichi Shiraishi, Kenichi Chiba, Hiroko Tanaka, Satoru Miyano, Seishi Ogawa, Seiji Kojima, Shigeaki Nonoyama, Tomohiro Morio, Hirokazu Kanegane, Abnormal hematopoiesis and autoimmunity in human subjects with germline IKZF1 mutations, JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY, 10.1016/j.jaci.2016.09.029, 140, 1, 223-231, 2017.07, Background: Ikaros, which is encoded by IKZF1, is a transcriptional factor that play a critical role in hematopoiesis. Somatic IKZF1 alterations are known to be involved in the pathogenesis of leukemia in human subjects. Recently, immunodeficiency caused by germline IKZF1 mutation has been described.
Objective: We sought to describe the clinical and immunologic phenotypes of Japanese patients with heterozygous IKZF1 mutations.
Methods: We performed whole-exome sequencing in patients from a dysgammaglobulinemia or autoimmune disease cohort and used a candidate gene approach in 4 patients. Functional and laboratory studies, including detailed lymphopoiesis/hematopoiesis analysis in the bone marrow, were performed.
Results: Nine patients from 6 unrelated families were identified to have heterozygous germline mutations in IKZF1. Age of onset was 0 to 20 years (mean, 7.4 years). Eight of 9 patients presented with dysgammaglobulinemia accompanied by B-cell deficiency. Four of 9 patients had autoimmune disease, including immune thrombocytopenic purpura, IgA vasculitis, and systemic lupus erythematosus. Nonautoimmune pancytopenia was observed in 1 patient. All of the mutant Ikaros protein demonstrated impaired DNA binding to the target sequence and abnormal diffuse nuclear localization. Flow cytometric analysis of bone marrow revealed reduced levels of common lymphoid progenitors and normal development of pro-B to pre-B cells.
Conclusions: Germline heterozygous IKZF1 mutations cause dysgammaglobulinemia; hematologic abnormalities, including B-cell defect; and autoimmune diseases..
|143.||Hideki Muramatsu, Yusuke Okuno, Kenichi Yoshida, Yuichi Shiraishi, Sayoko Doisaki, Atsushi Narita, Hirotoshi Sakaguchi, Nozomu Kawashima, Xinan Wang, Yinyan Xu, Kenichi Chiba, Hiroko Tanaka, Asahito Hama, Masashi Sanada, Yoshiyuki Takahashi, Hitoshi Kanno, Hiroki Yamaguchi, Shouichi Ohga, Atsushi Manabe, Hideo Harigae, Shinji Kunishima, Eiichi Ishii, Masao Kobayashi, Kenichi Koike, Kenichiro Watanabe, Etsuro Ito, Minoru Takata, Miharu Yabe, Seishi Ogawa, Satoru Miyano, Seiji Kojima, Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes, GENETICS IN MEDICINE, 10.1038/gim.2016.197, 19, 7, 796-802, 2017.07, Purpose: Precise genetic diagnosis of inherited bone marrow failure syndromes (IBMFS), a heterogeneous group of genetic disorders, is challenging but essential for precise clinical decision making.
Methods: We analyzed 121 IBMFS patients using a targeted sequencing covering 184 associated genes and 250 IBMFS patients using whole-exome sequencing (WES).
Results: We achieved successful genetic diagnoses for 53 of 121 patients (44%) using targeted sequencing and for 68 of 250 patients (27%) using WES. In the majority of cases (targeted sequencing: 45/53, 85%; WES: 63/68, 93%), the detected variants were concordant with, and therefore supported, the clinical diagnoses. However, in the remaining 13 cases (8 patients by target sequencing and 5 patients by WES), the clinical diagnoses were incompatible with the detected variants.
Conclusion: Our approach utilizing targeted sequencing and WES achieved satisfactory diagnostic rates and supported the efficacy of massive parallel sequencing as a diagnostic tool for IBMFS..
|144.||Hirofumi Inoue, Shin-ichi Terachi, Takeshi Uchiumi, Tetsuji Sato, Michiyo Urata, Masataka Ishimura, Yui Koga, Taeko Hotta, Toshiro Hara, Dongchon Kang, Shouichi Ohga, The clinical presentation and genotype of protein C deficiency with double mutations of the protein C gene, PEDIATRIC BLOOD & CANCER, 10.1002/pbc.26404, 64, 7, 2017.07, BackgroundSevere protein C (PC) deficiency is a rare heritable thrombophilia leading to thromboembolic events during the neonatal period. It remains unclear how individuals with complete PC gene (PROC) defects develop or escape neonatal stroke or purpura fulminans (PF).
ProcedureWe studied the onset of disease and the genotype of 22 PC-deficient patients with double mutations in PROC based on our cohort (n = 12) and the previous reports (n = 10) in Japan.
ResultsTwenty-two patients in 20 unrelated families had 4 homozygous and 18 compound heterozygous mutations. Sixteen newborns presented with PF (n = 11, 69%), intracranial thromboembolism and hemorrhage (n = 13, 81%), or both (n = 8, 50%), with most showing a plasma PC activity of <10%. Six others first developed overt thromboembolism when they were over 15 years of age, showing a median PC activity of 31% (range: 19-52%). Fifteen of the 22 patients (68%) had the five major mutations (G423VfsX82, V339M, R211W, M406I, and F181V) or two others (E68K and K193del) that have been reported in Japan. Three of the six late-onset cases, but none of the 16 neonatal cases, had the K193del mutation, which has been reported to be the most common variant of Chinese thrombophilia. A novel mutation of A309V was determined in a family of two patients with late onset.
ConclusionsThe genotype of double-PROC mutants might show less diversity than heterozygous mutants in terms of the timing of the onset of thrombophilia (newborn onset or late onset)..
|145.||Shouichi Ohga, Diagnostic challenge of Diamond-Blackfan anemia in mothers and children by whole-exome sequencing, INTERNATIONAL JOURNAL OF HEMATOLOGY, 10.1007/s12185-016-2151-7, 105, 4, 515-520, 2017.04.|
|146.||Diagnostic challenge of Diamond-Blackfan anemia in mothers and children by whole-exome sequencing..|
|147.||Intractable Back Pain After Coil Embolization of Giant Veno-Venous Collaterals in a Patient With Fontan Circulation..|
|148.||Etsuro Nanishi, Takayuki Hoshina, Hisanori Nishio, Murasaki Aman, Akio Sakamoto, Shouichi Ohga, Toshiro Hara, Intramuscular Venous Malformation in an Infant Masquerading as Recurrent Gonarthritis, PEDIATRICS AND NEONATOLOGY, 10.1016/j.pedneo.2015.10.013, 58, 2, 185-186, 2017.04.|
|149.||Shouichi Ohga, Exome sequencing identified RPS15A as a novel causative gene for Diamond-Blackfan anemia, HAEMATOLOGICA, 10.3324/haematol.2016.153932, 102, 3, E93-E96, 2017.03.|
|150.||Fumika Ikeda, Kenichi Yoshida, Tsutomu Toki, Tamayo Uechi, Shiori Ishida, Yukari Nakajima, Yoji Sasahara, Yusuke Okuno, Rika Kanezaki, Kiminori Terui, Takuya Kamio, Akie Kobayashi, Takashi Fujita, Aiko Sato-Otsubo, Yuichi Shiraishi, Hiroko Tanaka, Kenichi Chiba, Hideki Muramatsu, Hitoshi Kanno, Shouichi Ohga, Akira Ohara, Seiji Kojima, Naoya Kenmochi, Satoru Miyano, Seishi Ogawa, Etsuro Ito, Exome sequencing identified RPS15A as a novel causative gene for Diamond-Blackfan anemia, HAEMATOLOGICA, 10.3324/haematol.2016.153932, 102, 3, E93-E96, 2017.03.|
|151.||Activated phosphoinositide 3-kinase δ syndrome presenting with gut-associated T-cell lymphoproliferative disease..|
|152.||Shouichi Ohga, Involuntary movements and coma as the prognostic marker for acute encephalopathy with biphasic seizures and late reduced diffusion, JOURNAL OF THE NEUROLOGICAL SCIENCES, 10.1016/j.jns.2016.09.018, 370, 39-43, 2016.11.|
|153.||Involuntary movements and coma as the prognostic marker for acute encephalopathy with biphasic seizures and late reduced diffusion..|
|154.||Two infants with tuberculid associated with Kawasaki disease..|
|155.||A nationwide survey of common viral infections in childhood among patients with primary immunodeficiency diseases..|
|156.||Shouichi Ohga, Blood Reference Intervals for Preterm Low-Birth-Weight Infants: A Multicenter Cohort Study in Japan, PLOS ONE, 10.1371/journal.pone.0161439, 11, 8, 2016.08.|
|157.||Shouichi Ohga, JAK2, MPL, and CALR mutations in children with essential thrombocythemia, INTERNATIONAL JOURNAL OF HEMATOLOGY, 10.1007/s12185-016-2022-2, 104, 2, 266-267, 2016.08.|
|158.||Shouichi Ohga, Blood Reference Intervals for Preterm Low-Birth-Weight Infants: A Multicenter Cohort Study in Japan, PLOS ONE, 10.1371/journal.pone.0161439, 11, 8, 2016.08.|
|159.||Sekiya Y, Okuno Y, Muramatsu H, Ismael O, Kawashima N, Narita A, Wang X, Xu Y, Hama A, Fujisaki H, Imamura T, Hasegawa D, Kosaka Y, Sunami S, Ohtsuka Y, Ohga S, Takahashi Y, Kojima S, Shimada A, JAK2, MPL, and CALR mutations in children with essential thrombocythemia., International journal of hematology, 10.1007/s12185-016-2022-2, 104, 2, 266-7, 2016.08.|
|160.||Shouichi Ohga, SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7, NATURE GENETICS, 10.1038/ng.3569, 48, 7, 792-+, 2016.07, Adrenal hypoplasia is a rare, life-threatening congenital disorder. Here we define a new form of syndromic adrenal hypoplasia, which we propose to term MIRAGE (myelodysplasia, infection, restriction of growth, adrenal hypoplasia, genital phenotypes, and enteropathy) syndrome. By exome sequencing and follow-up studies, we identified 11 patients with adrenal hypoplasia and common extra-adrenal features harboring mutations in SAMD9. Expression of the wild-type SAMD9 protein, a facilitator of endosome fusion, caused mild growth restriction in cultured cells, whereas expression of mutants caused profound growth inhibition. Patient-derived fibroblasts had restricted growth, decreased plasma membrane EGFR expression, increased size of early endosomes, and intracellular accumulation of giant vesicles carrying a late endosome marker. Of interest, two patients developed myelodysplasitc syndrome (MDS) that was accompanied by loss of the chromosome 7 carrying the SAMD9 mutation. Considering the potent growth-restricting activity of the SAMD9 mutants, the loss of chromosome 7 presumably occurred as an adaptation to the growth-restricting condition..|
|161.||Coronary artery lesions and the increasing incidence of Kawasaki disease resistant to initial immunoglobulin..|
|162.||Erythrocyte glutathione is a novel biomarker of Diamond-Blackfan anemia..|
|163.||SAMD9 mutations cause a novel multisystem disorder, MIRAGE syndrome, and are associated with loss of chromosome 7..|
|164.||ATP11C is a major flippase in human erythrocytes and its defect causes congenital hemolytic anemia..|
|165.||Adjunct cyclosporine therapy for refractory Kawasaki disease in a very young infant..|
|166.||Shouichi Ohga, Memory B-Cell Pools Predict the Immune Response to Pneumococcal Conjugate Vaccine in Immunocompromised Children., THE JOURNAL OF INFECTIOUS DISEASES, 10.1093/infdis/jiv469, 213, 5, 848-855, 2016.03.|
|167.||A Sporadic Neonatal Case of Epidermolysis Bullosa Simplex Generalized Intermediate with KRT5 and KRT14 Gene Mutations..|
|168.||Masako Ichiyama, Shouichi Ohga, Masayuki Ochiai, Kotaro Fukushima, Masataka Ishimura, Michiko Torio, Michiyo Urata, Taeko Hotta, Dongchon Kang, Toshiro Hara, Fetal hydrocephalus and neonatal stroke as the first presentation of protein C deficiency, BRAIN & DEVELOPMENT, 10.1016/j.braindev.2015.07.004, 38, 2, 253-256, 2016.02, Severe protein C-deficiency is a rare heritable thrombophilia of the newborn. Infants with biallelic PROC mutations present purpura fulminans and intracranial thromboembolism, while the prenatal onset of mutated heterozygotes remains unclear. We herewith present the first case of fetal ventriculomegaly and neonatal stroke associated with heterozygous PROC mutation. The infant was born to a healthy mother at 38 gestational weeks. The fetal growth had been normal, but the routine ultrasound screening had indicated mild hydrocephalus at 28 weeks of gestation. He developed convulsions two days after birth. Computed tomography of the brain revealed multiple hemorrhagic infarctions and ventriculomegaly. Dissociated levels of the plasma activity between protein C (21%) and protein S (42%) reached to determine the heterozygote of PROC c.574_576delAAG, a common thrombophilic predisposition in Asian ancestries. PC-mutant heterozygotes may have a limited high risk of cerebral thromboembolism during the perinatal course. (C) 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved..|
|169.||ALDH2 polymorphism in patients with Diamond-Blackfan anemia in Japan..|
|170.||Masako Ichiyama, Shouichi Ohga, Masayuki Ochiai, Koichi Tanaka, Yuka Matsunaga, Takeshi Kusuda, Hirosuke Inoue, Masataka Ishimura, Tomohito Takimoto, Yui Koga, Taeko Hotta, Dongchon Kang, Toshiro Hara, Age-specific onset and distribution of the natural anticoagulant deficiency in pediatric thromboembolism, PEDIATRIC RESEARCH, 10.1038/pr.2015.180, 79, 1, 81-86, 2016.01, BACKGROUND: The early diagnosis of inherited thrombophilia in children is challenging because of the rarity and hemostatic maturation.
METHODS: We explored protein C (PC), protein S (PS), and antithrombin (AT) deficiencies in 306 thromboembolic patients aged <= 20 y using the screening of plasma activity and genetic analysis.
RESULTS: Reduced activities were determined in 122 patients (40%). Low PC patients were most frequently found in the lowest age group (0-2 y, 45%), while low PS or low AT patients were found in the highest age group (16-20 y; PS: 30% and AT: 20%). Genetic study was completed in 62 patients having no other causes of thromboembolism. Mutations were determined in 18 patients (8 PC, 8 PS, and 2 AT genes). Six of eight patients with PC gene mutation were found in age 0-2 y (75%), while six of eight patients with PS gene mutation were in 7-20 y. Two AT gene-mutated patients were older than 4 y. Four PC-deficient and two PS-deficient patients carried compound heterozygous mutations. All but one PC gene-mutated patient suffered from intracranial thromboembolism, while PS/AT gene-mutated patients mostly developed extracranial venous thromboembolism.
CONCLUSION: Stroke in low PC infants and deep vein thrombosis in low PS/AT school age children could be targeted for genetic screening of pediatric thrombophilias..
|171.||Erratum to: Long-term liposteroid therapy for idiopathic pulmonary hemosiderosis..|
|172.||Comparison of long-term outcomes between children with aplastic anemia and refractory cytopenia of childhood who received immunosuppressive therapy with antithymocyte globulin and cyclosporine..|
|173.||Successful control of juvenile dermatomyositis-associated macrophage activation syndrome and interstitial pneumonia: distinct kinetics of interleukin-6 and -18 levels..|
|174.||Remission of autoimmune neutropenia after development of Kawasaki disease..|
|175.||In vivo hepatogenic capacity and therapeutic potential of stem cells from human exfoliated deciduous teeth in liver fibrosis in mice..|
|176.||Takayuki Hoshina, Shouichi Ohga, Junko Fujiyoshi, Etsuro Nanishi, Tomoko Takimoto, Shunsuke Kanno, Hisanori Nishio, Mitsumasa Saito, Yukihiro Akeda, Kazunori Oishi, Toshiro Hara, Memory B-Cell Pools Predict the Immune Response to Pneumococcal Conjugate Vaccine in Immunocompromised Children, The Journal of Infectious Diseases, 10.1093/infdis/jiv469, 213, 848-855, 2015.09.|
|177.||Narita A, Muramatsu H, Sekiya Y, Okuno Y, Sakaguchi H, Nishio N, Yoshida N, Wang X, Xu Y, Kawashima N, Doisaki S, Hama A, Takahashi Y, Kudo K, Moritake H, Kobayashi M, Kobayashi R, Ito E, Yabe H, Ohga S, Ohara A, Kojima S, Paroxysmal nocturnal hemoglobinuria and telomere length predicts response to immunosuppressive therapy in pediatric aplastic anemia., Haematologica, 10.3324/haematol.2015.132530, 2015.08.|
|178.||Sasagu Kimura, Shunji Hasegawa, Masashi Yanagihara, Hirofumi Inoue, Takeshi Matsushige, Hidehiro Tsuneoka, Takashi Ichiyama, Shouichi Ohga, Cat-scratch disease with severe pleuritis in a 6-year-old girl, PEDIATRICS INTERNATIONAL, 10.1111/ped.12680, 57, 3, 501-503, 2015.06, We present the case of a 6-year-old girl with cat-scratch disease (CSD), who developed severe pleuritis without lymphadenitis. Bartonella henselae DNA was detected on real-time polymerase chain reaction (PCR) analysis of whole blood. This is the first report of CSD diagnosed on real-time PCR using whole blood..|
|179.||Acute pericardial effusion representing the TNF-α-mediated severe inflammation but not the coronary artery outcome of Kawasaki disease..|
|180.||Loss of function mutations in RPL27 and RPS27 identified by whole-exome sequencing in Diamond-Blackfan anaemia..|
|181.||Etsuro Nanishi, Takayuki Hoshina, Shouichi Ohga, Hisanori Nishio, Toshiro Hara, Drug reaction with eosinophilia and systemic symptoms during primary Epstein-Barr virus infection, JOURNAL OF MICROBIOLOGY IMMUNOLOGY AND INFECTION, 10.1016/j.jmii.2014.06.012, 48, 1, 109-112, 2015.02, We report a drug reaction with eosinophilia and systemic symptoms case of primary Epstein-Barr virus (EBV) infection, in which the diagnosis was first confirmed by lymphocyte transformation tests (LTT). LTTs were positive for cefditoren-pivoxil and acetaminophen. LTT, EBV load, and anti-EBV antibodies could allow early diagnosis of drug reaction with eosinophilia and systemic symptoms, which masquerades with the clinical features of infectious mononucleosis. Copyright (C) 2014, Taiwan Society of Microbiology. Published by Elsevier Taiwan LLC. All rights reserved..|
|182.||Kenichiro Yamamura, Hidetoshi Takada, Kiyoshi Uike, Yasutaka Nakashima, Yuichiro Hirata, Hazumu Nagata, Tomohito Takimoto, Masataka Ishimura, Eiji Morihana, Shouichi Ohga, Toshiro Hara, Early progression of atherosclerosis in children with chronic infantile neurological cutaneous and articular syndrome, RHEUMATOLOGY, 10.1093/rheumatology/keu180, 53, 10, 1783-1787, 2014.10, Objective. Chronic inflammation plays a key role in the development of atherosclerosis. Early progression of atherosclerosis has been reported in patients with RA. Cryopyrin-associated periodic syndromes (CAPS) are autosomal dominant autoinflammatory disorders caused by heterozygous NLRP3 gene mutations. Chronic infantile neurological cutaneous and articular (CINCA) syndrome is the most severe form of CAPS and patients display early onset of rash, fever, uveitis and joint manifestations. However, there has been no previous report on atherosclerosis in patients with CAPS. The objective of this study is to assess the development of atherosclerosis in patients with CINCA syndrome.
Methods. Intima-media thickness (IMT) of the carotid arteries, stiffness parameter beta, ankle brachial index (ABI) and pressure wave velocity (PWV) were evaluated by ultrasonography in 3 patients with CINCA syndrome [mean age 9.0 years (S. D. 5.3)] and 19 age-matched healthy controls [9.3 years (S. D. 4.3)].
Results. The levels of carotid IMT, stiffness parameter b and PWV in CINCA syndrome patients were significantly higher than those in healthy controls [0.51 mm (S. D. 0.05) vs 0.44 (0.04), P = 0.0021; 6.1 (S. D. 1.7) vs 3.9 (1.0), P = 0.0018; 1203 cm/s (S. D. 328) vs 855 (114), P = 0.017, respectively].
Conclusion. Patients with CINCA syndrome showed signs of atherosclerosis from their early childhood. The results of this study emphasize the importance of chronic inflammation in the development of atherosclerosis. Further analysis on atherosclerosis in young patients with CINCA syndrome may provide more insights into the pathogenesis of cardiovascular disease..
|183.||Yuhki Koga, Hidetoshi Takada, Aiko Suminoe, Shouichi Ohga, Toshiro Hara, Successful treatment of non-Hodgkin's lymphoma using R-CHOP in a patient with Wiskott-Aldrich syndrome followed by a reduced-intensity stem cell transplant, PEDIATRIC TRANSPLANTATION, 10.1111/petr.12297, 18, 6, E208-E211, 2014.09, WAS is an X-linked primary immunodeficiency characterized by microthrombocytopenia, eczema, recurrent infections, and increased incidence of autoimmunity and malignancy. HSCT is the only curative treatment for WAS. Herein, we report the case of a 17-yr-old boy with WAS who received an unrelated HSCT while in complete remission of diffuse large B-cell lymphoma after chemotherapy. Pretransplant conditioning consisted of fludarabine, busulfan, and total body irradiation (4 Gy). GvHD prophylaxis consisted of tacrolimus and short-course methotrexate. Following HSCT, rapid and stable engraftment was observed. Platelet count gradually increased, and the generalized eczema improved. The patient developed grade II acute GvHD and limited chronic GvHD on days 30 and 210, respectively, which resolved with immunosuppressive treatment. Symptoms caused by the reactivation of human herpes virus-6, BK virus, and VZV were observed from days 21, 60, and 96, respectively; they were resolved after conservative treatment and acyclovir administration. No other regimen-related toxicity was observed. Complete donor bone marrow chimerism was achieved one month after transplantation. RIST is an effective therapeutic option for older children with WAS accompanied by malignant lymphoma..|
|184.||Peripheral blood lymphocyte telomere length as a predictor of response to immunosuppressive therapy in childhood aplastic anemia..|
|185.||Staphylococcal endocarditis as the first manifestation of heritable protein S deficiency in childhood..|
|186.||Mitsuharu Fukazawa, Takayuki Hoshina, Etsuro Nanishi, Hisanori Nishio, Takehiko Doi, Shouichi Ohga, Toshiro Hara, Neonatal hemophagocytic lymphohistiocytosis associated with a vertical transmission of coxsackievirus B1, JOURNAL OF INFECTION AND CHEMOTHERAPY, 10.1007/s10156-013-0629-2, 19, 6, 1210-1213, 2013.12, Hemophagocytic lymphohistiocytosis (HLH) is a life-threatening syndrome characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy with the background of hypercytokinemia. Early diagnosis and etoposide therapy are not established for affected newborns. An afebrile infant suffered from apnea 4 days after birth, showing leukocytosis, thrombocytopenia, coagulopathy, and cerebrospinal fluid pleocytosis. Serum levels of ferritin and sIL-2R were high. Bone marrow studies revealed activated/hemophagocytosing macrophages. Coxsackievirus B1 (CB1) was isolated from the throat and stool. Serum anti-CB1 antibody titers were elevated in the patient (4 -> 16; 6 -> 43 days after birth) and mother (128; 10 days after delivery). Normal expressions of perforin and CD107a precluded inherited HLH. The vertically transmitted CB1-HLH was successfully treated without administration of corticosteroid, cyclosporine, or etoposide. Serum cytokine levels showed dominant expression of monokines (IL-1 beta/6/8, and TNF-alpha) but not IFN-gamma, which is the central player of inherited HLH. The cytokine profile might represent a unique pathophysiology of enterovirus-driven neonatal HLH..|
|187.||Long-term liposteroid therapy for idiopathic pulmonary hemosiderosis..|
|188.||Clinical characteristics and outcomes of chédiak-Higashi syndrome: a nationwide survey of Japan..|
|189.||Limited renal prophylaxis in regular plasmatherapy for heritable ADAMTS13 deficiency..|
|190.||Kenichiro Yamamura, Kunitaka Joo, Shouichi Ohga, Hazumu Nagata, Kazuyuki Ikeda, Jun Muneuchi, Mamie Watanabe, Toshiro Hara, Thrombocytosis in asplenia syndrome with congenital heart disease: A previously unrecognized risk factor for thromboembolism, INTERNATIONAL JOURNAL OF CARDIOLOGY, 10.1016/j.ijcard.2012.06.009, 167, 5, 2259-2263, 2013.09, Background: Thrombocytosis and thromboembolic complications occur after splenectomy. However, there is no previous report investigating the presence of thrombocytosis and its association with thromboembolic events in patients having asplenia syndrome with congenital heart disease.
Methods: Enrolled were 161 consecutive patients with functionally single ventricle who underwent cardiac catheterization between 1997 and 2010. They were divided into two groups: patients having asplenia (Group A, n = 46) and patients having no asplenia (Group B, n = 115). Aspirin therapy was employed in all patients after surgical interventions except for pulmonary artery banding. We retrospectively reviewed the platelet counts at each seven stage of cardiac catheterization (for pre- and postoperative evaluation of the first palliation, Glenn operation, and Fontan operation, and for late evaluation after Fontan operation), incidence of thromboembolic events, and other possible risk factors for thromboembolism.
Results: The median platelet counts in Group A were consistently higher than those in Group B at any of the seven stages of cardiac catheterizations (p<0.002). The incidence of thromboembolic complications was also higher in Group A than that in Group B (28% vs. 10%, p = 0.030). Univariate and multivariate logistic regression analyses showed that a platelet count of more than 550x10(9)/L at the first cardiac catheterization was associated with thromboembolic complications (Odds ratio 3.17; p = 0.046).
Conclusions: Persistent thrombocytosis is present in patients with asplenia syndrome. It may greatly contribute to the development of thromboembolism during the management of congenital heart disease than expected. (C) 2012 Elsevier Ireland Ltd. All rights reserved..
|191.||Bilateral stenosis of carotid siphon in Hutchinson-Gilford progeria syndrome..|
|192.||Akihisa Sawada, Shouichi Ohga, Eiichi Ishii, Masami Inoue, Keiko Okada, Jiro Inagaki, Hiroaki Goto, Nobuhiro Suzuki, Kazutoshi Koike, Yoshiko Atsuta, Ritsuro Suzuki, Hiromasa Yabe, Keisei Kawa, Koji Kato, Koji Yasutomo, Feasibility of reduced-intensity conditioning followed by unrelated cord blood transplantation for primary hemophagocytic lymphohistiocytosis: a nationwide retrospective analysis in Japan, INTERNATIONAL JOURNAL OF HEMATOLOGY, 10.1007/s12185-013-1391-z, 98, 2, 223-230, 2013.08, A nationwide retrospective analysis was performed on patients who received allogeneic hematopoietic stem cell transplantation for primary or familial hemophagocytic lymphohistiocytosis (HLH) in Japan. The present analysis investigated whether reduced-intensity conditioning (RIC) followed by cord blood transplantation (CBT) (RIC-CBT) is feasible, compared to the outcomes of myeloablative conditioning and bone marrow transplantation. Based on the JSHCT data, 53 patients were analyzed. The overall survival rate (OS) was 65.4 +/- A 6.6 %. RIC-CBT (n = 13) was not inferior to other methods. Patients with a performance status of PS 4 (ECOG scale) with HLH-associated severe organ dysfunction during the initiation of conditioning had extremely poor outcomes. The OS rate in the RIC-CBT patients, excluding those with a performance status 4, was 80.0 +/- A 12.6 %. RIC may reduce treatment-related mortality; in addition, patients with engraftment failure, which is the main adverse event following RIC-CBT, were successfully rescued with secondary CBT. Unrelated cord blood may represent an alternative source if a patient has no related donor. As a RIC regimen for CBT, 140 mg/m(2) melphalan with fludarabine and anti-lymphocyte globulin or anti-thymocyte globulin may be feasible, but further dosage optimization should be performed in controlled clinical trials..|
|193.||Masataka Ishimura, Hiroyuki Yamamoto, Yumi Mizuno, Hidetoshi Takada, Motohiro Goto, Takehiko Doi, Takayuki Hoshina, Shouichi Ohga, Koichi Ohshima, Toshiro Hara, A Non-invasive Diagnosis of Histiocytic Necrotizing Lymphadenitis by Means of Gene Expression Profile Analysis of Peripheral Blood Mononuclear Cells, JOURNAL OF CLINICAL IMMUNOLOGY, 10.1007/s10875-013-9897-y, 33, 5, 1018-1026, 2013.07, Histiocytic necrotizing lymphadenitis (HNL), also called Kikuchi-Fujimoto disease, is a benign, self-limiting inflammatory disease with fever and painful cervical lymphadenopathy of unknown etiology. A lymph node biopsy is required for the definitive diagnosis because of no specific symptoms or laboratory findings for HNL. To establish the rapid non-invasive diagnostic method for this disease, we investigated genes specifically expressed in the patients by analyzing whole transcriptome using microarray analysis of peripheral blood mononuclear cells (PBMC). The top five upregulated genes (IFI44L, CXCL10, GBP1, EPSTI1 and IFI27) in HNL were interferon-induced genes (ISGs). The expression levels of the up-regulated genes by microarray were verified by quantitative PCR. High levels of serum CXCL10 concentration were confirmed at the symptomatic phase of HNL patients. The expression levels of these 5 genes positively correlated with each other (r(2)=0.28-0.60). The genes were also highly expressed in HNL lymph nodes. The discriminant analysis using the expression levels of these five genes distinguished HNL with 84 % accuracy. The combination of upregulated ISGs in HNL seemed to be a specific response induced by viral infections or autoantigens. An analysis of the gene expression profile of PBMC may provide a rapid non-invasive diagnosis of HNL..|
|194.||Protein C deficiency as the major cause of thrombophilias in childhood..|
|195.||Hirosuke Inoue, Shouichi Ohga, Takeshi Kusuda, Junko Kitajima, Tadamune Kinjo, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Toshiro Hara, Serum neutrophil gelatinase-associated lipocalin as a predictor of the development of bronchopulmonary dysplasia in preterm infants., Early human development, 10.1016/j.earlhumdev.2012.12.011, 89, 6, 425-9, 2013.06, BACKGROUND: Bronchopulmonary dysplasia (BPD) is a chronic lung disease mostly occurring in preterm infants. The pathogenesis of BPD involves early inflammation and remodeling of the premature lung. AIM: To search for the novel predictive marker of BPD development, we studied serum levels of neutrophil gelatinase-associated lipocalin (NGAL), an innate immune mediator, in preterm infants. METHODS: Serum NGAL concentrations at birth were measured by enzyme-linked immunosorbent assay. The reference levels were determined in 52 infants having no anomalies or inherited diseases. The levels and clinical variables were assessed in association with BPD. RESULTS: Geometric means (95%CI) of serum NGAL levels at birth of infants having no underlying diseases were 32.4 (22.1-47.5), 58.6 (47.9-71.8), and 126.2 (99.0-168.7) ng/mL for <31, 31-36 and >36 gestational weeks (GW), respectively (p<0.001). These levels positively correlated with neutrophil (p<0.0001) or monocyte counts (p<0.0001). The median NGAL levels (307.8 ng/mL) and neutrophil counts (4141/μL) at birth of 16 preterm infants (<31 GW) who developed BPD were higher than those (42.9 ng/mL and 1357/μL) of 20 infants (<31 GW) who did not (p<0.0001 and p=0.012), respectively. In multivariable analysis for 36 infants born less than 31 GW, higher NGAL levels (≥ 82 ng/mL) but not neutrophil counts at birth had a significant association with developing BPD (gestational-age adjusted odds ratio [OR]=37.45 [3.08-455.49], p<0.01). CONCLUSIONS: High serum levels of NGAL at birth could be an early sensitive marker for BPD in preterm infants, because their levels were physiologically low..|
|196.||Paediatric presentation and outcome of congenital protein C deficiency in Japan..|
|197.||Rabbit antithymocyte globulin and cyclosporine as first-line therapy for children with acquired aplastic anemia..|
|198.||Immunosuppressive Therapy with Antithymocyte Globulin and Cyclosporine for Fulminant Aplastic Anemia.|
|199.||Hypothyroidism and levothyroxine-responsive liver dysfunction in a patient with ring chromosome 18 syndrome..|
|200.||Akira Shiraishi, Shouichi Ohga, Takehiko Doi, Masataka Ishimura, Tomohito Takimoto, Hidetoshi Takada, Toshihiro Miyamoto, Yasunobu Abe, Toshiro Hara, Treatment choice of immunotherapy or further chemotherapy for Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis, PEDIATRIC BLOOD & CANCER, 10.1002/pbc.24039, 59, 2, 265-270, 2012.08, Background EpsteinBarr virus-associated hemophagocytic lymphohistiocytosis (EBV-HLH) leads to an aggressive and often fatal course without appropriate treatment. Etoposide therapy is crucial for the better prognosis, although it remains unknown what patients need cytotoxic agents. Since we have complied with step-up strategy in a tertiary center, treatment outcomes were studied to search predictors for disease course. Methods The study enrolled 22 EBV-HLH patients treated between 1999 and 2010 in Kyushu University. Immunotherapy, chemotherapy and stem cell transplantation (SCT) proceeded in stages unless patients attained a consecutive >21 days-afebrile remission. Clinical and laboratory data and outcomes were retrospectively analyzed. Results Median age of 9 males and 13 females was 5 years (range: 9 months41 years). Sixteen patients (73%) presented at age <15 years. Two patients remitted spontaneously, 12 attained remissions after immunotherapy, 5 after chemotherapy, and 1 after successful SCT. The remaining two patients died after chemotherapy and SCT, respectively. Median EBV load was 1 x 105?copies/ml of peripheral blood (range: 2005 x 107). T-cells were exclusively targeted (94%; 15/16 examined) often with EBV/T-cell receptor clonality. EBV status indicated 19 primary infections and 3 reactivations. Either death occurred in EBV-reactivated patients who underwent chemotherapy +/- SCT. Age at primary infection in pediatric patients increased in the last 5 years. Patients having prolonged fever (P?=?0.017) or high soluble CD25 levels (P?=?0.017) at diagnosis were at higher risk for requiring chemotherapy assessed by multivariate analyses. Conclusions No cytotoxic agents were needed for >60% of EBV-HLH patients. Early immunotherapy may modulate T-cell activation and reduce the chance of unnecessary chemotherapy. Pediatr Blood Cancer 2012;59:265270. (c) 2011 Wiley Periodicals, Inc..|
|201.||Takeshi Asano, Kazuhiro Kogawa, Akira Morimoto, Yasushi Ishida, Nobuhiro Suzuki, Shouichi Ohga, Kazuko Kudo, Shigeru Ohta, Hiroshi Wakiguchi, Ken Tabuchi, Shunichi Kato, Eiichi Ishii, Hemophagocytic lymphohistiocytosis after hematopoietic stem cell transplantation in children: A nationwide survey in Japan, Pediatric Blood and Cancer, 10.1002/pbc.23384, 59, 1, 110-114, 2012.07, Background: Hemophagocytic lymphohistiocytosis (HLH) is associated with hypercytokinemia in children. Although HLH can be also observed after hematopoietic stem cell transplantation (HSCT), the incidence and clinical features of HLH after HSCT remain obscure. Procedure: The clinical features of HLH after HSCT (post-HSCT HLH) were investigated in children with malignancies, immune deficiencies, or aplastic anemia. The HLH/Langerhans Cell Histiocytosis (LCH) Committee of the Japanese Society of Pediatric Hematology (JSPH) sent questionnaires to hospitals with JPSH members asking for details of cases in which HLH occurred after HSCT between 1998 and 2008. Results: Among 42 children who were diagnosed with post-HSCT HLH between 1998 and 2008 in Japan, 37 fulfilled our inclusion criteria
of these, 26 were classified as early-onset (onset <
30 days after HSCT) and 11 were classified as late-onset (onset >
30 days after HSCT). In the early-onset group, the presence of respiratory symptoms, high levels of total bilirubin, and triglycerides at onset and the lack of control of GVHD with tacrolimus were significantly associated with non-resolution of HLH (P<
0.05). The survival rate was significantly higher in patients with resolution of HLH than in those without resolution (59% vs. 14%, P<
0.05). Conclusions: These findings suggest that early-onset post-HSCT HLH is a specific entity of HLH, and appropriate diagnosis and prompt management need to be established. © 2011 Wiley Periodicals, Inc..
|202.||Masanori Nishi, Ryosei Nishimura, Nobuhiro Suzuki, Akihisa Sawada, Takayuki Okamura, Naoto Fujita, Rie Kanai, Jun Yano, Souichi Adachi, Takahiro Yasumi, Emiko Sato, Koji Yasutomo, Eiichi Ishii, Shouichi Ohga, Reduced-intensity conditioning in unrelated donor cord blood transplantation for familial hemophagocytic lymphohistiocytosis, AMERICAN JOURNAL OF HEMATOLOGY, 10.1002/ajh.23190, 87, 6, 637-639, 2012.06, Familial hemophagocytic lymphohistiocytosis (FHL) is a disorder of immune homeostasis characterized by fever, cytopenias, hepatosplenomegaly, and coagulopathy. We studied the outcomes of 13 FHL patients who underwent the first unrelated cord blood transplantation (UCBT) after non-myeloablative conditionings. The major regimen consisted of fludarabine (FLU; n = 12)+melphalan (MEL; n = 11)+/- low-dose total body irradiation (TBI 2-4 Gy; n = 6). The median age at presentation and period to UCBT were 6 and 5 months, respectively. Central nervous system (CNS) disease developed in one infant at diagnosis, and in two others until UCBT. HLH activity was controlled in all but one at the time of UCBT. Ten patients had early engraftment on median day 21 with no grade >2 treatment-related toxicity and two controllable grade >2 acute GVHD. Two patients with early rejection successfully underwent subsequent UCBT after myeloablative conditioning. Two others had late graft failure following mixed donor chimerism. Two deaths occurred from HLH; early liver failure and late CNS disease. Of 11 FLU+MEL-conditioned patients, the frequency of disease-free complete engraftment was higher for MEL (=120 mg/m2)+TBI, or high-dose MEL (180 mg/m2) than for others (83% vs. 25%, p = 0.036). The FLU+MEL-based non-myeloablative regimen was acceptable for FHL infants undergoing UCBT, although further studies will be needed for confirmation. Am. J. Hematol. 87:637639, 2012. (c) 2012 Wiley Periodicals, Inc..|
|203.||Tracheal aspirate gene expression in preterm newborns and development of bronchopulmonary dysplasia..|
|204.||Junko Kitajima, Hirosuke Inoue, Shouichi Ohga, Tadamune Kinjo, Masayuki Ochiai, Takahisa Yoshida, Koichi Kusuhara, Toshiro Hara, Differential Transmission and Postnatal Outcomes in Triplets with Intrauterine Cytomegalovirus Infection, PEDIATRIC AND DEVELOPMENTAL PATHOLOGY, 10.2350/11-05-1034-CR.1, 15, 2, 151-155, 2012.03, We present a case of triplets with intrauterine cytomegalovirus (CMV) infection, each of whom showed differential transmission, placental pathology, and postnatal outcome. The first-and second-born infants were both vigorous and asymptomatic at birth, although the first-, but not the second-born, triplet had a high copy number of CMV DNA in the peripheral blood (1.2 x 10(3) copy/mL). The third-born triplet suffered from symptomatic CMV infection with a high viral load (6.0 x 10(6) copy/mL). The triamniotic-trichorionic placentas were not fused to each other. The histopathologic analysis showed that CMV-positive cells were frequently found in the decidua, villi, and amnion of the third-born triplet's placenta but were limited and scattered in the decidua or villi but not amnion of the other 2 placentas. The third-born triplet underwent ganciclovir therapy. None of the infants had physical or auditory problems at 4 years of age, whereas the third-born triplet had been diagnosed with an autistic disorder. This observation exemplifies the preventive roles of the individual placentas of triplets with regard to virus infection, thus suggesting that developing CMV disease largely depends on the placental function..|
|205.||A neonate with inherited protein C deficiency first suspected of having gluteal hemangioma and Kasabach-Merritt syndrome.|
|206.||Antithymocyte Globulin (ATG), Cyclosporine (CyA), and Danazol Versus ATG and CyA As Treatment for Children with Aplastic Anemia: Result of Matched-Pair Analysis.|
|207.||Imadome K, Yajima M, Arai A, Nakagawa-Nakazawa A, Kawano F, Ichikawa S, Shimizu N, Yamamoto N, Morio T, Ohga S, Nakamura H, Ito M, Miura O, Komano J, Fujiwara S, CD4+T cells have a critical role in the proliferation of EBV-infected T and NK cells, PLOS Pathogen, 7, 10, e1002326, 2011.10.|
|208.||Ken-Ichi Imadome, Misako Yajima, Ayako Arai, Atsuko Nakazawa, Fuyuko Kawano, Sayumi Ichikawa, Norio Shimizu, Naoki Yamamoto, Tomohiro Morio, Shouichi Ohga, Hiroyuki Nakamura, Mamoru Ito, Osamu Miura, Jun Komano, Shigeyoshi Fujiwara, Novel mouse xenograft models reveal a critical role of CD4 + T cells in the proliferation of ebv-infected T and NK cells, PLoS Pathogens, 10.1371/journal.ppat.1002326, 7, 10, 2011.10, Epstein-Barr virus (EBV), a ubiquitous B-lymphotropic herpesvirus, ectopically infects T or NK cells to cause severe diseases of unknown pathogenesis, including chronic active EBV infection (CAEBV) and EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH). We developed xenograft models of CAEBV and EBV-HLH by transplanting patients' PBMC to immunodeficient mice of the NOD/Shi-scid/IL-2Rγ null strain. In these models, EBV-infected T, NK, or B cells proliferated systemically and reproduced histological characteristics of the two diseases. Analysis of the TCR repertoire expression revealed that identical predominant EBV-infected T-cell clones proliferated in patients and corresponding mice transplanted with their PBMC. Expression of the EBV nuclear antigen 1 (EBNA1), the latent membrane protein 1 (LMP1), and LMP2, but not EBNA2, in the engrafted cells is consistent with the latency II program of EBV gene expression known in CAEBV. High levels of human cytokines, including IL-8, IFN-γ, and RANTES, were detected in the peripheral blood of the model mice, mirroring hypercytokinemia characteristic to both CAEBV and EBV-HLH. Transplantation of individual immunophenotypic subsets isolated from patients' PBMC as well as that of various combinations of these subsets revealed a critical role of CD4 + T cells in the engraftment of EBV-infected T and NK cells. In accordance with this finding, in vivo depletion of CD4 + T cells by the administration of the OKT4 antibody following transplantation of PBMC prevented the engraftment of EBV-infected T and NK cells. This is the first report of animal models of CAEBV and EBV-HLH that are expected to be useful tools in the development of novel therapeutic strategies for the treatment of the diseases. © 2011 Imadome et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..|
|209.||Yamamura K, Ohga S, Nishiyama K, Doi T, Tsutsumi Y, Ikeda K, Fujishima A, Takada H, Hara T
, Recurrent atrial fibrillation after high-dose methylprednisolone therapy in a girl with lupus-associated hemophagocytic syndrome
, Lupus 2011 (in press) , 2011.07.
|210.||Ohga S, Ishimura M, Yoshimoto G, Miyamoto T, Takada H, Tanaka T, Ohshima K, Ogawa Y, Imadome K, Abe Y, Akashi K, Hara T, Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood
, J Clin Virol 51(1):31-7, 2011, 2011.07.
|211.||Kamio T, Ito E, Ohara A, Kosaka Y, Tsuchida M, Yagasaki H, Mugishima H, Yabe H, Morimoto A, Ohga S, Muramatsu H, Hama A, Kaneko T, Nagasawa M, Kikuta A, Osugi Y, Bessho F, Nakahata T, Tsukimoto I, Kojima S
, Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group:
, Haematologica 2011 (in press), 2011.07.
|212.||Eljaafari FM, Takada H, Tanaka T, Doi T, Ohga S, Hara T
, Potent induction of IFN-γ production from cord blood NK cells by the stimulation with single-strand RNA
, J Clin Immunol 2011 (in press), 2011.07.
|213.||K. Yamamura, S. Ohga, K. Nishiyama, T. Doi, Y. Tsutsumi, K. Ikeda, A. Fujishima, H. Takada, T. Hara, Recurrent atrial fibrillation after high-dose methylprednisolone therapy in a girl with lupus-associated hemophagocytic syndrome, LUPUS, 10.1177/0961203310392429, 20, 8, 871-875, 2011.07, Hemophagocytic syndrome (HPS) is a serious complication of systemic lupus erythematosus (SLE). A 15-year-old female with lupus-nephritis developed HPS. Bone marrow study showed florid thrombophagocytosis. There was no associated infection. High-dose methylprednisolone therapy ameliorated HPS. However, atrial fibrillation (Af) repeated after the infusion and required direct-current cardioversion. No underlying diseases were found in the heart and endocrine system. Chest roentgenogram and echocardiography were normal. Electrocardiogram showed slightly prolonged PR interval in sinus rhythm. Af occurred at high circulating levels of interferon-gamma and interleukin (IL)-10, but not IL-6, IL-2, tumor necrosis factor-alpha, C-reactive protein or catecholamines. This is the first observation that high-dose corticosteroid induced Af in a case of lupus-HPS. Af is unusual in SLE children without cardiac disease, while conduction defect occurs associated with lupus-myocarditis. Lupus-HPS may be an aggressive SLE subset with cardiac involvement. High-dose corticosteroid infusion controls lupus activity, but could disclose the cardiac stress in lupus-HPS patients. Lupus (2011) 20, 871-875..|
|214.||Kinjo T, Ohga S, Ochiai M, Honjo S, Tanaka T, Takahata Y, Ihara K, Hara T, Serum chemokine levels and developmental outcome in preterm infants, Early Human Development 6(87):439-43, 2011, 2011.06.|
|215.||Takuya Kamio, Etsuro Ito, Akira Ohara, Yoshiyuki Kosaka, Masahiro Tsuchida, Hiroshi Yagasaki, Hideo Mugishima, Hiromasa Yabe, Akira Morimoto, Shouichi Ohga, Hideki Muramatsu, Asahito Hama, Takashi Kaneko, Masayuki Nagasawa, Atsushi Kikuta, Yuko Osugi, Fumio Bessho, Tatsutoshi Nakahata, Ichiro Tsukimoto, Seiji Kojima, Relapse of aplastic anemia in children after immunosuppressive therapy: a report from the Japan Childhood Aplastic Anemia Study Group, HAEMATOLOGICA-THE HEMATOLOGY JOURNAL, 10.3324/haematol.2010.035600, 96, 6, 814-819, 2011.06, Background
Although the therapeutic outcome of acquired aplastic anemia has improved markedly with the introduction of immunosuppressive therapy using antithymocyte globulin and cyclosporine, a significant proportion of patients subsequently relapse and require second-line therapy. However, detailed analyses of relapses in aplastic anemia children are limited.
Design and Methods
We previously conducted two prospective multicenter trials of immunosuppressive therapy for children with aplastic anemia: AA-92 and AA-97, which began in 1992 and 1997, respectively. In this study, we assessed the relapse rate, risk factors for relapse, and the response to second-line treatment in children with aplastic anemia treated with antithymocyte globulin and cyclosporine.
From 1992 to 2007, we treated 441 children with aplastic anemia with standard immunosuppressive therapy. Among the 264 patients who responded to immunosuppressive therapy, 42 (15.9%) relapsed. The cumulative incidence of relapse was 11.9% at 10 years. Multivariate analysis revealed that relapse risk was significantly associated with an immunosuppressive therapy regimen using danazol (relative risk, 3.15; P=0.001) and non-severe aplastic anemia (relative risk, 2.51; P=0.02). Seventeen relapsed patients received additional immunosuppressive therapy with antithymocyte globulin and cyclosporine. Eight patients responded within 6 months. Seven of nine non-responders to second immunosuppressive therapy received hematopoietic stem cell transplantation and five are alive. Eleven patients underwent hematopoietic stem cell transplantation directly and seven are alive.
In the present study, the cumulative incidence of relapse at 10 years was relatively low compared to that in other studies mainly involving adult patients. A multicenter prospective study is warranted to establish optimal therapy for children with aplastic anemia..
|216.||Serum chemokine levels and developmental outcome in preterm infants..|
|217.||Clonal origin of Epstein-Barr virus (EBV)-infected T/NK-cell subpopulations in EBV-positive T/NK-cell lymphoproliferative disorders of childhood..|
|218.||Kusuda T, Hikino S, Ohga S, Kinjo T, Ochiai M, Takahata Y, Tokunaga S, Ihara K, Hata Y, Hara T, Genetic variation of vascular endothelial growth factor pathway does not correlate with the severity of retinopathy of prematurity, J Perinatol 31(4):246-50, 2011, 31(4):, 246-50, 2011.04.|
|219.||Kitajima J, Ohga S, Kinjo T, Ochiai M, Takahata Y, Honjo S, Hara T, Serum prohepcidin concentrations at birth and one month after birth in premature infants, Pediatric Blood & Cancer, 10.1002/pbc.22773. Epub 2010 Sep 9., 56, (2), 267-72, 2011.02.|
|220.||Junko Kitajima, Shouichi Ohga, Tadamune Kinjo, Masayuki Ochiai, Yasushi Takahata, Satoshi Honjo, Toshiro Hara, Serum Prohepcidin Concentrations at Birth and 1 Month After Birth in Premature Infants, PEDIATRIC BLOOD & CANCER, 10.1002/pbc.22773, 56, 2, 267-272, 2011.02, Background. Premature newborns are vulnerable to iron imbalance, although the iron homeostasis during the perinatal period remains unclear. To clarify the iron metabolism of premature infants, we measured serum prohepcidin concentrations of preterm infants, and analyzed the association with iron parameters. Methods. Seventy-one (61 preterm and 10 term) infants were enrolled for the study, that had no underlying diseases including asphyxia, bleedings, infection, and anomalies. Serum concentrations of prohepcidin at birth and 1 month after birth were determined by enzyme-linked immunosorbent assay. Results. Prohepcidin levels at birth but not 1 month postnatal age positively correlated with gestational age (correlation coefficient [CC]:0.334, P=0.005) and birth weight (CC: 0.367, P=0.002). The levels at birth of preterm infants (median: 29.93 ng/ml, range: 4.0-110.6) were lower than those of full-term infants, and increased thereafter. On the other hand, the levels in small-for-gestational age infants were not associated with gestational age or birth weight. Prohepcidin levels at birth correlated positively with red cell counts (CC = 0.487, P=0.025), unsaturated iron binding capacity (CC = 0.755, P=0.001), total protein (CC = 0.624, P=0.005), and serum albumin levels (CC = 0.500, P = 0.025), and negatively with serum iron levels (CC = -0.688, P = 0.003), but not ferritin levels. Multivariate analyses indicated that prohepcidin levels at birth were lower in infants with pregnancy-induced hypertension (P = 0.03) or premature rupture of membrane (P = 0.01). Conclusions. Prohepcidin production was physiologically low at birth of preterm infants according to the gestational age, and the levels might be susceptible to the in utero stress. The postnatal increase might reflect the maturation and/or adaptation of iron homeostasis. Pediatr Blood Cancer 2011;56:267-272. (C) 2010 Wiley-Liss, Inc..|
|221.||Kudo K, Ohga S, Morimoto A, Ishida Y, Suzuki N, Hasegawa D, Nagatoshi Y, Kato S, Ishii E., Improved outcome of refractory Langerhans cell histiocytosis in children with hematopoietic stem cell transplantation in Japan., Bone Marrow Transplant 45(5):901-906, 2010, 45, 5, 901-906, 2010.12.|
|222.||H. Takada, A. Nomura, M. Ishimura, M. Ichiyama, S. Ohga, T. Hara, NEMO mutation as a cause of familial occurrence of Behcet's disease in female patients, CLINICAL GENETICS, 10.1111/j.1399-0004.2010.01432.x, 78, 6, 575-579, 2010.12, Behcet's disease is a chronic, relapsing, multisystem inflammatory disease of unknown etiology. Nuclear factor kappa B (NF-kappa B) essential modulator (NEMO) that is required for the activation of NF-kappa B plays an important role in inflammation. To investigate the role of NEMO in the pathogenesis of Behc, et's disease, we analyzed NEMO gene and its expression pattern in tissues in a family with Behc, et's disease. We found a heterozygous mutation (1217A>T, D406V) in a 6-year-old girl and her mother. Skewed X-chromosome inactivation was not observed in the peripheral blood mononuclear cells as well as in oral and intestinal mucosa of the patients. Accordingly, there was a significant proportion of peripheral blood monocytes that did not produce sufficient intracellular tumor necrosis factor-alpha with the stimulation of lipopolysaccharide. Heterozygous NEMO mutation is a cause of familial occurrence of Behc, et's disease in female patients..|
|223.||Michiko Torio, Masataka Ishimura, Shouichi Ohga, Takehiko Doi, Rina Utsunomiya, Kazuhiro Ohkubo, Naohiro Suga, Katsunori Tatsugami, Takayuki Matsumoto, Hidetoshi Takada, Toshiro Hara, Nephrolithiasis as an extra-intestinal presentation of pediatric inflammatory bowel disease unclassified, JOURNAL OF CROHNS & COLITIS, 10.1016/j.crohns.2010.05.012, 4, 6, 674-678, 2010.12, Urolithiasis is quite rare in pediatric inflammatory bowel disease (IBD) compared with the incidence at 9-18% in adult cases. The diagnosis and treatment of pediatric IBD is challenging. Indeterminate colitis (IC), originally proposed as a subgroup of fulminant IBD, has also been used for patients when the diagnosis of either UC or CD cannot be made with certainty. Such patients should be diagnosed as having "IBD unclassified" based on evidence including mucosal biopsy samples. We report herewith a 9-year-old boy with isolated colitis that reached a diagnosis of IBD unclassified. Infliximab therapy led to a successful remission after the refractory course. However, urolithiases were impacted in the urethral valves and vesico-ureteral junction. Microhematuria was noticed from the onset of colitis. Renal calculi were detected on the X-ray films during the first line treatment. Transurethrally crushed stones consisted of calcium oxalate. Renal calculi are more closely associated with CD than ulcerative colitis in adult patients for the ileal involvement. The oxalate stones and treatment response indicated a CD-like pathophysiology. Nephrolithiasis might be a rare but noticeable extra-intestinal presentation of pediatric IBD. Infliximab therapy could be an option in pediatric refractory colitis to change the critical steroid dependency. (C) 2010 European Crohn's and Colitis Organisation. Published by Elsevier B.V. All rights reserved..|
|224.||Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia..|
|225.||Torio M, Ishimura M, Ohga S, Doi T, Utsunomiya R, Ohkubo K, Suga N, Tatsugami K, Matsumoto T, Takada H, Hara T, Nephrolithiasis as an extra-intestinal presentation of pediatric inflammatory bowel disease unclassified, J Crohns Colitis 4(6):674-678, 2010, 2010.07.|
|226.||Ohga S, Kudo K, Ishii E, Honjo S, Morimoto A, Osugi Y, Sawada A, Tabuchi T, Suzuki N, Ishida Y, Imashuku S, Kato S, Hara T, for The HLH/LCH and SCT Committees in the Japanese Society of Pediatric Hematology:, Hematopoietic stem cell transplantation for familial hemophagocytic lymphohistiocytosis and Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in Japan., Pediatric Blood & Cancer 54(2):299-306, 2010, 2010.05.|
|227.||K. Kudo, S. Ohga, A. Morimoto, Y. Ishida, N. Suzuki, D. Hasegawa, Y. Nagatoshi, S. Kato, E. Ishii, Improved outcome of refractory Langerhans cell histiocytosis in children with hematopoietic stem cell transplantation in Japan, BONE MARROW TRANSPLANTATION, 10.1038/bmt.2009.245, 45, 5, 901-906, 2010.05, Langerhans cell histiocytosis (LCH) that is refractory to conventional chemotherapy has a poor outcome. Hematopoietic stem cell transplanta tion (SCT) is a promising approach for refractory LCH because of its immunomodulatory effect. In this study, the outcomes of children with refractory LCH undergoing SCT in Japan were analyzed. Between November 1995 and March 2007, 15 children younger than 15 years (9 males, 6 females) with refractory LCH underwent SCT. The patients' median age at diagnosis was 8 months (range, 28 days to 28 months), and all had failed conventional chemotherapy. The median age at SCT was 23 months (range, 13-178 months). Nine had risk organ involvement at diagnosis, including liver (n = 6), spleen (n = 5), lung (n = 5), and/or hematopoietic system (n = 4). For SCT, a myeloablative regimen was used for 10 patients, and a reduced-intensity conditioning regimen (RIC) was used for five. The donor source varied among the patients, but allogeneic cord blood was primarily used (n = 10). Subsequently, 11 of 15 patients have survived with no evidence of disease, with a 10-year overall survival (OS) rate (median +/- standard error) of 73.3 +/- 11.4%. The 10-year OS rate of nine patients with risk organ involvement at diagnosis was 55.6 +/- 16.6%, whereas six without risk organ involvement have all survived with no evidence of disease (P = 0.07). These results indicate that SCT is promising as a salvage approach for children with refractory LCH. Bone Marrow Transplantation (2010) 45, 901-906; doi: 10.1038/bmt.2009.245; published online 21 September 2009.|
|228.||Konno Y, Toki T, Tandai S, Xu G, Wang R, Terui K, Ohga S, Hara T, Hama A, Kojima S, Hasegawa D, Kosaka Y, Yanagisawa R, Koike K, Kanai R, Imai T, Hongo T, Park MJ, Sugita K, Ito E., Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia., Haematologica 95(8):1293-9, 2010, 2010.04.|
|229.||Takada H, Nomura A, Ishimura M, Ichiyama M, Ohga S, Hara T., NEMO mutation as a cause of familial occurrence of Behçet's disease in female patients., Clin Genet 78(6):575-9, 2010, 2010.03.|
|230.||Morimoto A, Ishida Y, Suzuki N, Ohga S, Shioda Y, Okimoto Y, Kudo K, Ishii E, Nationwide survey of single-system single site Langerhans cell histiocytosis in Japan., Pediatric Blood & Cancer, 54, 1, 98-102, 2010.01.|
|231.||Ishimura M, Ohga S, Ichiyama M, Kusuhara K, Takada H, Hara T, Takahashi M, Okamoto H., Hepatitis-associated aplastic anemia during a primary infection of genotype 1a torque teno virus., Eur J Pediatr 169(7): 899-902, 2010, 2009.12.|
|232.||Ohnishi K, Shioyama Y, Nomoto S, Sasaki T, Ohga S, Yoshitake T, Toba T, Atsumi K, Shiinoki T, Terashima H, Honda H, Spontaneous pneumothorax after stereotactic radiotherapy for non-small-cell lung cancer, Jpn J Radiol, 10.1007/s11604-009-0333-4, 27, 7, 264-274, 2009.08.|
|233.||Disseminated Bacillus Calmette-Guérin lymphadenitis in a patient with gp91phox- chronic granulomatous disease 25 years after vaccination..|
|234.||Fulminant sepsis/meningitis due to Haemophilus influenzae in a protein C-deficient heterozygote treated with activated protein C therapy..|
|235.||Kusuhara K, Ohga S, Hoshina T, Saito M, Sasaki Y, Ishimura M, Takada H, Fujita M, Hara T, Disseminated Bacillus Calmette-Guérin lymphadenitis in a patient with gp91phox (-) chronic granulomatous disease 25 years after vaccination., Eur J Pediatr 168(6): 745-747, 2009, 2009.05.|
|236.||Katsuragi S, Ohga S, Horiuchi H, Hara T, Terao K, Ikeda T., Neonatal onset hemophagocytic lymphohistiocytosis in a premature infant., Pediatr Blood Cancer 53(2): 244-245, 2009, 2009.05.|
|237.||Suzuki N, Morimoto A, Ohga S, Kudo K, Ishida Y, Ishii E; HLH/LCH Committee of the Japanese Society of Pediatric Hematology:, Characteristics of hemophagocytic lymphohistiocytosis in neonates: a nationwide survey in Japan., J Pediatr 155(2):235-238, 2009, 2009.05.|
|238.||Muneuchi J, Ohga S, Ishimura M, Ikeda K, Yamaguchi K, Nomura A, Takada H, Abe Y, Hara T, Cardiovascular complications associated with chronic active epstein-barr virus infection., Pediatr Cardiol. 2009 Apr;30(3):274-81, 2009.04.|
|239.||Ohga S, Sanefuji M, Ishimura M, Nomura A, Torisu H, Kira R, Takada H, Mizuno Y, Kazuyama Y, Hara T., Epstein-Barr virus load in cerebrospinal fluid of patients with chronic active Epstein-Barr virus infection., Pediatr Infect Dis J. 2008 Nov;27(11):1027-30., 2008.11.|
|240.||Epstein-Barr virus load in cerebrospinal fluid of patients with chronic active Epstein-Barr virus infection..|
|241.||Relapse of Children with Aplastic Anemia after Immunosuppressive Therapy.|
|242.||Sato E, Ohga S, Kuroda H, Yoshiba F, Nishimura M, Nagasawa M, Inoue M, Kawa K., Allogeneic hematopoietic stem cell transplantation for Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan., Am J Hematol. 2008 Sep;83(9):721-7, 2008.09.|
|243.||Sanefuji M, Ohga S, Kira R, Nomura A, Torisu H, Takada H, Kusuhara K, Hara T., Epstein-Barr virus-associated meningoencephalomyelitis: intrathecal reactivation of the virus in an immunocompetent child., J Child Neurol. 2008 Sep;23(9):1072-7., 2008.09.|
|244.||Emiko Sato, Shouichi Ohga, Hiroshi Kuroda, Fumiaki Yoshiba, Miki Nishimura, Masayuki Nagasawa, Masami Inoue, Keisei Kawa, Allogeneic hematopoletic stem cell transplantation for Epstein-Barr virus-associated T/natural killer-cell lymphoproliferative disease in Japan, AMERICAN JOURNAL OF HEMATOLOGY, 10.1002/ajh.21247, 83, 9, 721-727, 2008.09, Epstein-Barr virus (EBV)-associated T/NK-cell lymphoproliferative disease (LPD) has been linked to several different disorders. Its prognosis is generally poor and a treatment strategy has yet to be established. There are reports, however, that hematopoietic stem cell transplantation (HSCT) can cure this disease. To clarify the current situation regarding allogeneic hematopoietic stem cell transplantation (allo-HSCT) for EBV-associated T/NK-LPD, a nationwide survey was performed in Japan. Data for 74 patients were collected. There were 42 cases of chronic active EBV infection (CAEBV), 10 cases of EBV-associated hemophagocytic lymphohistiocytosis (EBV-HLH), and 22 cases of EBV-associated lymphoma/leukemia (EBV-lymphoma/leukemia). Of those with CAEBV, 54% had the EBV-infected T-cell type and 59% with EBV-lymphoma/leukemia had the EBV-infected NK-cell type. Most patients with EBV-HLH and EBV-lymphoma/leukemia received allo-HSCT within 1 year after onset compared to only 14% of patients with CAEBV. The event-free survival (EFS) rate following allo-HSCT was 0.561 +/- 0.086 for CAEBV, 0.614 +/- 0.186 for EBV-HLH, and 0.309 +/- 0.107 for EBV-lymphoma/leukemia. The EFS of allo-HSCT with conventional conditioning was 0.488 +/- 0.074 and with reduced-intensity conditioning was 0.563 +/- 0.124. Thus, in a substantial number of cases, EBV-associated T/NK-LPD can be cured by either allogeneic conventional stem cell transplantation or reduced-intensity stem cell transplantation..|
|245.||Epstein-Barr virus-associated meningoencephalomyelitis: intrathecal reactivation of the virus in an immunocompetent child..|
|246.||Ochiai M, Nakayama H, Sato K, Iida K, Hikino S, Ohga S, Tsukimori K, Wake N, Masumoto K, Taguchi T, Hara T, Head circumference and long-term outcome in small-for-gestational age infants., J Perinat Med. 2008;36(4):341-7., 2008.08.|
|247.||Ohga S, Ideguchi H, Kato J, Ishimura M, Takada H, Harada N, Kawanaka H, Hattori Y, Kang D, Hamasaki N, Hara T., Thromboembolic complications in splenectomized patients with dominantly inherited beta-thalassemia., Acta Haematol. 2008;120(1):31-5., 2008.08.|
|248.||Takada H, Ishimura M, Inada H, Ohga S, Kusuhara K, Moroi Y, Furue M, Hara T, Lipopolysaccharide-induced monocytic cell death for the diagnosis of mild neonatal-onset multisystem inflammatory disease, J Pediatr. 2008 Jun;152(6):885-7, 2008.06.|
|249.||Hidetoshi Takada, Masataka Ishimura, Hiroko Inada, Shouichi Ohga, Koichi Kusuhara, Yoichi Moroi, Masutaka Furue, Toshiro Hara, Lipopolysaccharide-Induced Monocytic Cell Death for the Diagnosis of Mild Neonatal-Onset Multisystem Inflammatory Disease, Journal of Pediatrics, 10.1016/j.jpeds.2008.01.038, 152, 6, 885-e1, 2008.06, In this report, we describe a boy who showed mild symptoms of neonatal-onset multisystem inflammatory disease. Although his symptoms and laboratory findings were similar to those of systemic juvenile idiopathic arthritis, further examinations revealed papilledema, meningitis, and a NLRP3 mutation. His peripheral blood monocytes died within 24 hours after lipopolysaccharide stimulation, a test that may be useful for diagnosis even in mild cases. © 2008 Mosby, Inc. All rights reserved..|
|250.||Hoshina T, Yamaguchi Y, Ohga S, Kira R, Ishimura M, Takada H, Tanaka T, Hara T, Sjogren's syndrome-associated meningoencephalomyelitis: cerebrospinal fluid cytokine levels and therapeutic utility of tacrolimus, J Neurol Sci. 2008 Apr 15;267(1-2):182-6., 2008.04.|
|251.||Nagatomo T, Muta K, Ohga S, Ochiai M, Ohshima K, Hara T, Insulin-like growth factor-II: a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors, Exp Hematol. 2008 Apr;36(4):401-11, 2008.04.|
|252.||Taro Nagatomo, Koichiro Muta, Shouichi Ohga, Masayuki Ochiai, Koichi Ohshima, Toshiro Hara, Insulin-like growth factor-II: a novel autocrine growth factor modulating the apoptosis and maturation of umbilical cord blood erythroid progenitors, EXPERIMENTAL HEMATOLOGY, 10.1016/j.exphem.2007.12.009, 36, 4, 401-411, 2008.04, Objective. To search a novel function of erythroid progenitor cells circulating as the major nucleated cell population in umbilical cord blood (CB) cells.
Materials and Methods. Human CB-derived CD36(+) erythroid progenitors were subjected to cDNA microarray. Gene expression and biological property of CB-erythroid progenitors and adult peripheral blood (PB)-erythroid progenitors were compared by using real-time polymerase chain reaction (PCR) and serum-free culture system with erythropoietin (EPO).
Results. The microarray revealed 124-fold higher levels of insulin-like growth factor-II (IGF-II)gene expression in CB-CD36(+) erythroid progenitors than in stimulated lymphocytes of adult PB. Real-time PCR verified that IGF-II mRNA levels were highest in CB-CD36(+) erythroid progenitors compared to other CB- or adult PB-fractionated cells. When CB-CD36(+) erythroid progenitors were cultured with EPO in serum-free medium, anti-IGF-II-antibody (Ab) reduced the number of erythroid colonies. When CB- and adult PB-derived erythroid colony-forming cells (ECFCs) were cultured with interleukin-3, stem cell factor, and EPO, mRNA levels per cells of IGF-II peaked on day 12, but those of type 1 and type 2 receptors did not increase with ECFCs maturation. The maturation rate by IGF-II was higher in CB-ECFCs than in adult PB-ECFCs. The majority of CB-ECFCs expressed IGF-II protein. Anti-IGF-II-Ab, but not anti-IGF-I-Ab, reduced the number of CB-ECFCs in liquid culture with EPO. Anti-IGF-II-Ab accelerated apoptosis of ECFCs, assessed by dimethylthiazole tetrazolium bromide, bromodeoxyuridine, and flow cytometric analyses. ECFCs failed to attain full maturity in the presence of anti-IGF-II-Ab.
Conclusions. These results suggest that IGF-II is produced by erythroid progenitors themselves, and has a crucial role in fetal erythropoiesis by modulating apoptosis and maturation in an autocrine fashion. (C) 2008 ISEH - Society for Hematology and Stem Cells. Published by Elsevier Inc..
|253.||Sjogren's syndrome-associated meningoencephalomyelitis: cerebrospinal fluid cytokine levels and therapeutic utility of tacrolimus..|
|254.||Early-onset sarcoidosis mimicking refractory cutaneous histiocytosis..|
|255.||Kosaka Y, Yagasaki H, Sano K, Kobayashi R, Ayukawa H, Kaneko T, Yabe H, Tsuchida M, Mugishima H, Ohara A, Morimoto A, Otsuka Y, Ohga S, Bessho F, Nakahata T, Tsukimoto I, Kojima S; Japan Childhood Aplastic Anemia Study Group., Prospective multicenter trial comparing repeated immunosuppressive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia., Blood. 2008 Feb 1;111(3):1054-9., 2008.02.|
|256.||Yoshiyuki Kosaka, Hiroshi Yagasaki, Kimihiko Sano, Ryoji Kobayashi, Hiroshi Ayukawa, Takashi Kaneko, Hiromasa Yabe, Masahiro Tsuchida, Hideo Mugishima, Akira Hara, Akira Morimoto, Yoshitoshi Otsuka, Shouichi Ohga, Fumio Bessho, Tatsutoshi Nakahata, Ichiro Tsukimoto, Seiji Kojima, Prospective multicenter trial comparing repeated immunosuppressive therapy with stem-cell transplantation from an alternative donor as second-line treatment for children with severe and very severe aplastic anemia, BLOOD, 10.1182/blood-2007-08-099168, 111, 3, 1054-1059, 2008.02, We conducted a prospective multicenter study to compare the efficacy of repeated immunosuppressive therapy (IST) with stem-cell transplantation (SCT) from an alternative donor in children with acquired aplastic anemia (AA) who failed to respond to an initial course of IST. Patients with severe (n = 86) and very severe disease (n = 119) received initial IST consisting of antithymocyte globulin (ATG) and cyclosporine. Sixty patients failed to respond to IST after 6 months from the initial IST and were eligible for second-line treatment. Among them, 21 patients lacking suitable donors received a second course of IST. Three patients developed an anaphylactoid reaction to ATG and could not complete the second IST. A trilineage response was seen in only 2 of 18 (11%) evaluable patients after 6 months. Thirty-one patients received SCT from an alternative donor. At 5 years from the initiation of second-line therapy, the estimated failure- free survival (FFS), defined as survival with response, was 83.9% (+/- 16.1%, SD) in the SCT group compared with 9.5% (+/- 9.0%) in the IST group (P =.001). These results suggest that SCT from an alternative donor offers a better chance of IFFS than a second IST in patients not responding to an initial IST..|
|257.||Ochiai M, Hikino S, Yabuuchi H, Nakayama H, Sato K, Ohga S, Hara T, A new scoring system for computed tomography of the chest for assessing the clinical status of bronchopulmonary dysplasia, J Pediatr. 2008 Jan;152(1):90-5, 2008.01.|
|258.||Ishimura M, Ohga S, Nagatoshi Y, Okamura J, Tajiri T, Kohashi K, Oda Y, Takada H, Hara T, Malignant hepatic tumor occurring 10 yrs after a histocompatible sibling donor bone marrow transplantation for severe aplastic anemia., Pediatr Transplant. 2007 Dec;11(8):945-9., 2007.12.|
|259.||Hayashida M, Ogita K, Matsuura T, Takahashi Y, Nishimoto Y, Ohga S, Hara T, Soejima Y, Taketomi A, Maehara Y, Kohashi K, Tsuneyoshi M, Taguchi T:, Successful prolonged rituximab treatment for post-transplant lymphoproliferative disorder following living donor liver transplantation in a child.
, Pediatr Transplant. 2007 Sep;11(6):671-5., 2007.09.
|260.||Makoto Hayashida, Keiko Ogita, Toshiharu Matsuura, Yukiko Takahashi, Yuko Nishimotol, Shouichi Ohga, Toshiro Hara, Yuji Soejima, Akinobu Taketorni, Yoshihiko Maehara, Kenichi Kohash, Masazumi Tsuneyosh, Tornoaki Taguchi, Successful prolonged rituximab treatment for post-transplant lymphoproliferative disorder following living donor liver transplantation in a child, PEDIATRIC TRANSPLANTATION, 10.1111/j.1399-3046.2007.00714.x, 11, 6, 671-675, 2007.09, PTLD is a serious complication of immunosuppression in solid organ transplant recipients. The incidence of PTLD is significantly higher in pediatric recipients than in adult because children are often EBV-seronegative and they may develop primary EBV infection after transplantation. We herein describe a case of GI-PTLD who achieved a complete remission by prolonged rituximab, a chimeric monoclonal antibody against CD20, mono-therapy. A one-yr-old female underwent a LDLT for liver failure after having previously undergone the Kasai procedure for billary atresia. At sixty days following the transplantation. GI-PTLD developed. Withdrawal of immunosuppression and a Surgical resection were thus performed. A histopathological examination of tumor revealed atypical medium to large cell lymphoid proliferation with strong CD20 immunopositivity indicating their B-cell origin. Polymorphic PTLD was diagnosed. Rituximab was administered at a dose of 375 mg/m(2) once a week, and the monotherapy resulted in a complete remission after 34 administrations. Based on this case, rituximab appears to be beneficial as a first-line therapy for PTLD..|
|261.||Nationwide survey of hemophagocytic lymphohistiocytosis in Japan..|
|262.||Perforin gene mutations in adult-onset hemophagocytic lymphohistiocytosis..|
|263.||Ishii E, Ohga S, Imashuku S, Yasukawa M, Tsuda H, Miura I, Yamamoto K, Horiuchi H, Takada K, Ohshima K, Nakamura S, Kinukawa N, Oshimi K, Kawa K:, Nation-wide survey analysis of hemophagocytic lymphohistiocytosis (HLH) in Japan
, Int J Hematol 2007 (in press) , 2007.01.
|264.||Nagafuji K, Nonami A, Kumano T, Kikushige Y, Yoshimoto G, Takenaka K, Shimoda K, Ohga S, Yasukawa M, Horiuchi H, Ishii E, Harada M:, Perforin gene mutations in hemophagocytic lymphohistiocytosis with late-life onset
, Hematologica 2007 (in press) , 2007.01.
|265.||Hideki Nakayama, Shouichi Ohga, Eiichi Ishii, Takeshi Inamitsu, Kunio Kishida, A four-year-old girl with cough, haemoptysis and anaemia, ACTA PAEDIATRICA, 10.1080/08035250600796620, 95, 12, 1707-1709, 2006.12.|
|266.||S Ohga, K Ichino, K Goto, S Hattori, A Nomura, H Takada, K Nakamura, T Hara, Unrelated donor cord blood transplantation for childhood severe aplastic anemia after a modified conditioning, PEDIATRIC TRANSPLANTATION, 10.1111/j.1399-3046.2006.00486.x, 10, 4, 497-500, 2006.06, Treatment of severe aplastic anemia (SAA) patients who lack human leukocyte antigen (HLA)-matched donors and failed immunosuppressive therapy (IST) is challenging. Recently, umbilical cord blood transplantation (CBT) after non-myeloablative therapy has been reported in adult but not in childhood SAA. However, most cases resulted in mixed donor chimerism and incomplete hematological recovery. We reported an 11-yr-old girl with recurred SAA 5 yr after IST who underwent unrelated donor CBT after a modified regimen. This patient had renal and cardiac dysfunction, and lacked suitable bone marrow donors. The 3.9 x 10(7)/kg CB cells from an HLA one-locus mismatched unrelated donor were infused after conditioning with total body irradiation (5 Gy), melphalan (120 mg/m(2)), and fludarabin (120 mg/m(2)). Hematological recovery was favorable in complete chimerism. A major complication was only skin graft-versus-host disease (grade I). CB could be an alternate stem cell source for childhood SAA after modified preparative regimen..|
|267.||Ueda, I, E Ishii, A Morimoto, S Ohga, M Sako, S Imashuku, Correlation between phenotypic heterogeneity and gene mutational characteristics in familial hemophagocytic lymphohistiocytosis (FHL), PEDIATRIC BLOOD & CANCER, 10.1002/pbc.20511, 46, 4, 482-488, 2006.04, Background. Classification of familial hemophagocytic lympho-histiocytosis (FHL) into FHL2, FHL3, and other subtypes based on genetic abnormalities has recently become possible. We studied the phenotypic differences among these subtypes in Japan. Methods. Forty patients clinically diagnosed with FHL were analyzed. Perform abnormality was screened by flow cytometric analysis and/or DNA sequencing in these patients, and those without perform abnormalities were further examined for the presence of mutations in the Munc`13-4 gene by DNA sequencing. The correlation between clinical features and genetic subtypes was investigated. Results. Of the 40 HLH patients, 11 showed perform gene mutations (classified as FHL2) and ten had Munc13-4 gene mutations (FHL3), but neither mutation was noted in 19 patients (non-FHL2/3). Although the majority of the patients developed the disease before the age of 1 year, the onset in three FHL2 patients with missense mutations was late (7, 11, and 12 years). Incidence of deficient natural killer cell activity was higher in FHL2 patients (9/9 FHL2, 4/9 FHL3, and 6/17 non-FHL2/3; P=0.005). The serum levels of ferritin and soluble interleukin-2 receptor were significantly higher in FHL2 patients with nonsense perform mutations compared to other subgroups (P < 0.05). Epstein-Barr virus infection was involved in 8 of the 40 HLH patients: one FHL2, one FHL3, and six non-THI-2/3. Conclusions. Although clinical features of FHL3 appear to be homogeneous, the heterogeneous clinical features of FHL2 depend upon the nature of perforin gene mutations. Characterization of the non-FHL2/3 group with regard to FHL1 or other novel gene mutations remains to be conducted. Pediatr Blood Cancer 2006;46:482-488. (c) 2005 Wiley-Liss, Inc..|
|268.||Hara T, Ohga S, Hattori S, Hatano M, Kaku N, Nomura A, Takada H, Kokuba N, Hara T, Prolonged severe pancytopenia as the first manifestation of systemic juvenile xanthogranuloma, Pediatr Blood Cancer 47:103-106, 2006, 2006.01.|
|269.||Matsuura T, Sonoda K, Ohga S, Ishibashi T, A case of chronic recurrent uveitis associated with chronic granulomatous disease, Jap J Ophthalmol 50:287-289, 2006., 2006.01.|
|270.||Ueda I, Ishii E, Morimoto A, Ohga S, Sako M, Imashuku S, Phenotypic heterogeneity of familial hemophagocytic lymphohistiocytosis (FHL) in relation to gene mutational characteristics, Pediatr Blood & Cancer 46:482-488, 2006, 2006.01.|
|271.||Kanaya Y, Ohga S, Ikeda K, Furuno K, Ohno T, Takada H, Kinukawa N, Hara T:, Maturational alterations of peripheral T cell subsets and cytokine gene expression in chromosome 22q11.2 deletion syndrome.
, Clin Exp Immunol 144:85-89, 2006 , 2006.01.
|272.||Hikino S, Ohga S, Kanda T, Nakashima T, Yamamoto J, Nakayama H, Nakano H, Hara T:, Long -term outcome in twin -to-twin transfusion syndrome.
, Fetal Diag Ther 22:68-74, 2006 , 2006.01.
|273.||Koga Y, Ohga S, Nomura A, Takada H, Hara T:, Reduced gene expression of clustered ribosomal proteins in Diamond-Blackfan anemia patients without RPS19 gene mutations.
, J Pediatr Hematol Oncol 28:355-361, 2006, 2006.01.
|274.||Kobayashi R, Yabe H, Hara J, Morimoto A, Tsuchida M, Mugishima H, Ohara A, Tsukimoto I, Kato K, Kigasawa H, Tabuchi K, Nakahata T, Ohga S, Kojima S; the Japan Childhood Aplastic Anemia Study Group., Preceding immunosuppressive therapy with antithymocyte globulin and ciclosporin increases the incidence of graft rejection in children with aplastic anaemia who underwent allogeneic bone marrow transplantation from HLA-identical siblings.
, Br J Haematol 135:693-696, 2006, 2006.01.
|275.||Hatano M, Takada H, Nomura A, Ohga S, Ohshima K, Saeki I, Tajiri T, Taguchi T, Suita S, Hara T:, Epstein-Barr virus associated broncial leiomyoma in a boy with a cellular immunodeficiency.
, Pediatr Pulmonology 41:371-373, 2006 , 2006.01.
|276.||Ohga S, Ichino K, Goto K, Hattori S, Nomura A, Takada H, Nakamura K, Hara T:, Unrelated cord blood donor transplantation for childhood severe aplastic anemia after a modified conditioning.
, Pediatr Transplant 10:497-500, 2006 , 2006.01.
|277.||Toubo T, Ohga S, Takada H, Suga N, Nomura A, Ohno T, Hara T:, Rheumatic fever-mimicking carditis as a first presentation of chronic active Epstein-Barr virus infection., Acta Paediatr 95:614-618, 2006, 95:614-618, 2006, 2006.01.|
|278.||Nagata H, Ohga S, Hattori S, Masumoto K, Taguchi T, Matsumoto T, Hara T:, Barium-associated appendicitis in a childhood case with Crohn's disease.
, Acta Paediatr 95:889-890, 2006, 95:889-890, 2006
|279.||Nakayama H, Ohga S, Ishii E, Inamitsu T, Kishida K:, A four-year-old girl with cough, hemoptysis and anemia.
, Atca Paediatr 95:1707-1709, 2006, 95:1707-1709, 2006, 2006.01.
|280.||Ohga S, Nomura A, Takada H, Suga N, Hara T:, Successful self-infusion of activated prothrombin complex concentrate for prophylaxis in a child with a factor VIII inhibitor.
, Am J Hematol 82:145-149, 2007, 82:145-149, 2007, 2006.01.
|281.||M Ochiai, S Hikino, H Nakayama, S Ohga, T Taguchi, T Hara, Nonimmune hydrops fetalis due to generalized lymphatic dysplasia in an infant with Robertsonian trisomy 21, AMERICAN JOURNAL OF PERINATOLOGY, 10.1055/s-2005-918892, 23, 1, 63-66, 2006.01, We report the first case of generalized lymphatic dysplasia and trisomy 21 presenting with nonimmune hydrops fetalis. This infant showed intractable chylothorax, chylous ascites, and periodic bouts of edema. A karyotype analysis revealed Robertsonian trisomy 21: 46,XY,t(14q21q)(q10;q10) +21. This patient died of multiple organ failure at 400 days of life, despite the management of chylous effusions. The lymphoscintigraphy and histopathological findings led to the final diagnosis of generalized lymphatic dysplasia, which might also contribute to the development of hydrops. Refractory chylothorax in trisomy 21 patients may emphasize the need for intensive scrutiny of lymphatic disorders..|
|282.||Nomura A, Takada H, Ohga S, Ishii N, Inoue T, Hara T, T-cell-depleted CD34+ cell transplantation from an HLA-mismatched donor in a low-birth weight infant with X-linked severe combined immunodeficiency, J Pediatr Hematol Oncol 27:80-84, 2005, 10.1097/01.mph.0000152859.59880.54, 27, 2, 80-84, 27:80-84, 2005, 2005.01.|
|283.||Ishimura M, Ohga S, Nomura A, Toubo T, Morihana E, Saito Y, Nishio H, Ide M, Takada H, Hara T, Successful umbilical cord blood transplantation for severe chronic active Epstein-Barr virus infection after double failures of hematopoietic stem cell transplantation, Am J Haematol 80:204-206, 2005, 10.1002/ajh.20430, 80, 3, 207-212, 2005.01.|
|284.||Sanefuji M, Ohga S, Kira R, Yoshiura T, Hara T, Moyamoya syndrome in a splenectomized patient with β-thalassemia intermedia, J Child Neurol 21:75-77, 2006, 10.2310/7010.2006.00006, 21, 1, 75-77, 2005.01.|
|285.||Takada H, Saito Y, Nomura A, Ohga S, Nakashima N, Aishima S, Tsuru N, Hara T, Bronchiolitis obliterance organizing pneumonia as an initial manifestation in systemic lupus erythematosus, Pediatr Pulmonol 40:257-260, 2005, 10.1002/ppul.20224, 40, 3, 257-260, 40:257-260, 2005, 2005.01.|
|286.||Takada H, Kusuhara K, Nomura A, Ohga S, Hayashi M, Furue M, Hara T, A novel CIAS1mutation in a Japanese patient with chronic infantile neurological cutaneous and articular syndrome, Eur J Pediatr 164:785-786, 2005, 10.1007/s00431-005-1750-8, 164, 12, 785-786, 2005.01.|
|287.||Yamamoto K, Ishii E, Horiuchi H, Ueda I, Ohga S, Nishi M, Ogata Y, Zaitsu M, Morimoto A, Hara T, Imashuku S, Sasazuki T, Yasukawa M, Mutations of syntaxin 11 and SNAP23 genes as causes of familial hemophagocytic lymphohistiocytosis were not found in Japanese people, J Human Genet 50:600-603, 2005, 10.1007/s10038-005-0293-1, 50, 11, 600-603, 2005.01.|
|288.||Nagatomo T, Ohga S, Takada H, Nomura A, Hikino S, Imura M, Ohshima K, Hara T:, Microarray analysis of human milk cells: Persistent high expression of osteopontin during the lactating period., Clin Exp Immunol 138:47-53, 2004, 10.1111/j.1365-2249.2004.02549.x, 138, 1, 47-53, 2004.01.|
|289.||Yamamoto K, Ishii E, Sako M, Ohga S, Furuno K, Suzuki N, Ueda I, Imayoshi M, Yamamoto S, Morimoto A, Takada H, Hara T, Imashuku S, Sasazuki T, Yasukawa M:, MUNC13-4 mutations and cytotoxic function of MUNC13-4-deficient-T lymphocytes in familial hemophagocytic lymphohistiocytosis., J Med Genet 41:763-767, 2004, 41:763-767, 2004, 2004.01.|
|290.||Suzuki K, Ohshima K, Karube K, Suzumiya J, Ohga S, Ishihara S, Tamura K, Kikuchi M:, Clinicopathological states of Epstein-Barr virus-associated T/NK-cell lymphoproliferative disorders (severe chronic active EBV infection) of children and young adults., Int J Oncol 24:1165-74, 2004, 24, 5, 1165-1174, 24:1165-74, 2004, 2004.01.|
|291.||Takahata Y, Nomura A, Takada H, Ohga S, Hikino S, Nakayama H, Sakaguchi S, Hara T:, Human cord blood CD25+CD4+ T cells: a novel immunoregulatory population with naive phenotype., Exp Hematol 32:622-629, 2004, 2004.01.|
|292.||Ohga S, Nomura A, Takada H, Tanaka T, Furuno K, Takahata Y, Kinukawa N, Imai S, Hara T:, Dominant expression of interleukin-10 and transforming growth factor-β genes in activated T-cells of chronic active Epstein-Barr virus infection., J Med Virol 74:449-458, 2004, 10.1002/jmv.20197, 74, 3, 449-458, 74:449-458, 2004, 2004.01.|
|293.||Takada H, Ohga S, Mizuno Y, Nomura A, Hara T:, Increased IL-16 levels in hemophagocytic lymphohistiocytosis., J Pediatr Hematol/Oncol 26:567-573, 2004, 10.1097/01.mph.0000134465.86671.2e, 26, 9, 567-573, 26:567-573, 2004, 2004.01.|
|294.||Toubo T, Suga N, Ohga S, Nomura A, Onoe Y, Takada H, Morihana E, Hara T:, Successful unrelated cord blood transplantation for Epstein-Barr virus-associated lymphoproliferative disease with hemophagocytic syndrome., Int J Hematol 80:458-62, 2004, 10.1532/IJH97.04081, 80, 5, 458-462, 2004.01.|
|295.||S Ohga, A Nomura, H Takada, J Kato, H Ideguchi, Y Hattori, M Suda, S Suita, T Hara, Dominant beta-thalassemia with hemoglobin Hradec Kralove: Enhanced hemolysis in the spleen, INTERNATIONAL JOURNAL OF HEMATOLOGY, 78, 4, 329-334, 2003.11, We describe a 6-year-old girl and her mother with dominant beta-thalassemia due to hemoglobin Hradec Kralove (Hb HK). Both patients presented microcytic anemia, jaundice, splenomegaly, cholelithiasis, and recurrent hemolytic bouts. Osmotic resistance tests using saline and coiled planet centrifugation revealed the increased fragility of the red cell membrane. On the other hand, the glycerol lysing time was prolonged, and results of the isopropanol test were weakly positive. Despite mimicking the features of hereditary spherocytosis, the results of the genetic analyses verified the second reported family with Hb HK (codon 115, G (C) under barC [Ala]-->G (A) under barC [Asp]). Splenectomy was effective for the amelioration of hemolysis. Of 7 reported patients with Hb variants at beta-globin codon 115 (Hb Madrid and Hb HK), 5 underwent splenectomy. Because of the variable augmentation of extramedullary hemolysis in dominant beta-thalassemias, genotyping is necessary for determining the clinical indication of splenectomy. (C) 2003 The Japanese Society of Hematology..|
|296.||S Ohga, A Nomura, K Ihara, Y Takahata, N Suga, H Akeda, R Shibata, J Okamura, N Kinukawa, T Hara, Cytokine imbalance in hyper-IgE syndrome: reduced expression of transforming growth factor beta and interferon gamma genes in circulating activated T cells, BRITISH JOURNAL OF HAEMATOLOGY, 121, 2, 324-331, 2003.04, Hyper-IgE syndrome (HIES) is a primary immunodeficiency disease characterized by recurrent infections and marked immunoglobulin (Ig)E elevation. To assess the proper T-cell defects of HIES, the cytokine profile of naturally activated T cells was compared between HIES, atopic dermatitis and chronic granulomatous disease (CGD). Intracellular flow cytometric analysis after in vitro stimulation showed no difference in the proportion of interferon (IFN)gamma- or interleukin 4 (IL-4)-producing T cells among these diseases. Quantitative polymerase chain reaction (PCR) for the cytokine genes was performed using circulating highly fractionated HLA-DR+ and HLA-DR- T cells. The IFNgamma/IL-4 or IFNgamma/IL-10 ratios were lower in HLA-DR+ T cells of HIES than in CGD (P = 0.0106, 0.0445), but did not differ between HIES and atopy. The transforming growth factor-beta (TGFbeta)/IL-4 ratio in HLA-DR+ T cells of HIES was lower than that of atopy (0.0106) or CGD (0.0062). The TGFbeta/IL-4 ratio in HLA-DR- T cells of HIES was also lower than that of atopy (0.0285). Stepwise logistic regression analysis identified TGFbeta/IL-4 ratios in HLA-DR+ (0.0001) or HLA-DR- (0.0086) T cells as the most powerful parameters to distinguish HIES from atopy and/or CGD. Serum IgE levels negatively correlated with IFNgamma/IL-4 (0.0108), IFNgamma/IL-10 (0.0254), or TGFbeta/IL-4 (0.0163) ratios in HLA-DR+ , but not HLA-DR- , T cells. These results suggested that the in vivo activated T cells of HIES did not sufficiently express the IFNgamma and TGFbeta genes, which could affect IL-4-dependent IgE production. The reduced TGFbeta expression may involve the indigenous T-cell defects of HIES..|
|297.||Ohga S, Nomura A, Ihara K, Takahata Y, Akeda H, Shibata R, Okamura J, Kinukawa N, Hara T:, Cytokine imbalance in hyper-IgE syndrome: reduced expression of transforming growth factor-beta and interferon-gamma genes in circulating activated T cells, Br J Haematol 121:324-331, 2003, 10.1046/j.1365-2141.2003.04267.x, 121, 2, 324-331, 2003.01.|
|298.||Ohshima K, Karube K, Hamasaki M, Tutiya T, Yamaguchi T, Suefuji H, Suzuki K, Suzumiya J, Ohga S, Kikuchi M:, Differential chemokine, chemokine receptor and cytokine expression in Epstein-Barr virus-associated lymphoproliferative diseases, Leuk Lymphoma 44:1367-1378, 2003, 10.1080/1042819031000082984, 44, 8, 1367-1378, 2003.01.|
|299.||Ohga S, Nomura A, Takada H, Kato J, Ideguchi H, Hattori Y, Suda M, Suita S, Hara T:, Dominant beta-thalassemia with Hb Hradec Kralove: enhanced hemolysis in the spleen, Int J Hematol 78:329-334, 2003, 10.1007/BF02983557, 78, 4, 329-334, 2003.01.|
|300.||Takada H, Takahata Y, Nomura A, Ohga S, Mizuno Y, Hara T:, Increased serum levels of interferon-gamma-inducible protein 10 and monokine induced by gamma interferon in patients with hemophagocytic lymphohistiocytosis, Clin Exp Immunol 133:448-453, 2003, 10.1046/j.1365-2249.2003.02237.x, 133, 3, 448-453, 2003.01.|
|301.||Kimura H, Morishima T, Kanegane H, Ohga S, Hoshino Y, Maeda A, Imai S, Okano M, Morio T, Yokota S, Tsuchiya S, Yachie A, Imashuku S, Kawa K, Wakiguchi H, and Members of the Japanese Association for Research on Epstein-Barr Virus and related Diseases:, Prognostic factors for chronic active Epstein-Barr virus infection, J Infect Dis 187:527-533, 2003, 10.1086/367988, 187, 4, 527-533, 2003.01.|
|302.||Ishizaki Y, Tezuka J, Ohga S, Nomura N, Suga N, Kuromaru R, Kusuhara K, Mizuno Y, Kasuga N, Hara T:, Quantification of circulating varicella zoster virus-DNA for the early diagnosis of visceral varicella, J Infect 47:133-138, 2003, 10.1016/S0163-4453(03)00004-5, 47, 2, 133-138, 2003.01.|
|303.||Ohga S, Takada H, Nomura A, Hara T:, Lymphoproliferative Disease in Childhood: Clinical and biological role of cytokines, Research Advances in Blood by GLOBAL RESEARCH NETWORK, 27-37, 2003 , 2003.01.|
|304.||Ohga S, Nomura A, Takahata Y, Ihara K, Takada H, Wakiguchi H, Kudo Y, Hara T, Dominant expression of interleukin 10 but not interferon gamma in CD4(-)CD8(-)alphabetaT cells of autoimmune lymphoproliferative syndrome., British journal of haematology, 10.1046/j.1365-2141.2002.03848.x, 119, 2, 535-538, 2002.11.|
|305.||Distinct clinical phenotype and immunoreactivity in Japanese siblings with autoimmune polyglandular syndrome type 1 (APS-1) associated with compound heterozygous novel AIRE gene mutations..|
|306.||N Suga, H Takada, A Nomura, S Ohga, E Ishii, K Ihara, K Ohshima, T Hara, Perforin defects of primary haemophagocytic lymphohistiocytosis in Japan, BRITISH JOURNAL OF HAEMATOLOGY, 116, 2, 346-349, 2002.02, The perform gene was analysed in 15 Japanese patients with primary haemophagocytic lymphohistiocytosis (HLH). Perforin gene defects were found in two out of eight patients with familial IRE (FHL), and one out of seven without affected siblings. Four novel mutations were identified. Compound heterozygous mutations (one FHL and one sporadic HLH) and only one allele mutation (one FHL) were defined. Flow cytometry revealed no perform expression in CD8(+) or CD56(+) cells from a surviving patient with a mutation. The frequency of mutation was at least 20% of FHL in Japan. Flow cytometry for intracellular perforin may be useful for the screening of FHL2..|
|307.||Tsutsumi S, Ohga S, Nomura A, Takada H, Sakai S, Ohshima K, Sumimoto K, Hara T:, CD4-CD8- T-cell polymyositis in a patient with chronic active Epstein-Barr virus infection, Am J Hematol 71:211-215, 2002, 10.1002/ajh.10207, 71, 3, 211-215, 2002.01.|
|308.||Ohga S, Nomura A, Takahata Y, Ihara K, Takada H, Wakiguchi H, Kudo Y, Hara T:, Dominant expression of IL-10 but not IFN-gamma in CD4- CD8- alpha/beta T cells of autoimmune lymphoproliferative syndrome, Br J Haematol 119:535-538, 2002, 10.1046/j.1365-2141.2002.03848.x, 119, 2, 535-538, 2002.01.|
|309.||Ohga S, Nomura A, Takada H, Hara T:, Epstein-Barr virus associated diseases in childhood.-Immunological aspects of Epstein-Barr virus infection, Crit Rev Oncol Hematol 44:203-215, 2002, 2002.01.|
|310.||Ohga S, Nomura A, Takada H, Terao H, Harada N, Hara T:, Expansion of trisomy 8 and Sweet syndrome in a prolonged course of childhood aplastic anemia, J Pediatr Hematol/Oncol 24:64-68, 2002, 10.1097/00043426-200201000-00017, 24, 1, 64-68, 2002.01.|
|311.||Yamamoto M, Ohga S, Ohnishi Y, Inomata H:, Optic disk vasculitis associated with chronic active epstein-barr virus infection, Ophthalmologica 216:221-225, 2002, 10.1159/000059638, 216, 3, 221-225, 2002.01.|
|312.||Kogawa K, Kudoh J, Nagafuchi S, Katsuta H, Ohga S, Tamiya S, Sakai Y, Harada M, Hara T, Shimizu N:, Phenotype of autoimmune polyglandular syndrome type 1 and genotype of AIRE gene in a Japanese family, Clin Immunol 103:277-283, 2002, 2002.01.|
|313.||Ohga S, Ohara A, Hibi S, Kojima S, Bessho F, Tsuchiya S, Ohshima Y, Yoshida N, Kashii Y, Nishimura S, Kawakami K, Nishikawa K, Tsukimoto I for the Aplastic Anemia Committee of the Japanese Society of Pediatric Hematology:, Treatment responses of childhood aplastic anemia with chromosomal aberrations at diagnosis, Br J Haematol 118:313-319, 2002, 10.1046/j.1365-2141.2002.03582.x, 118, 1, 313-319, 2002.01.|
|314.||Ohga S, Nomura A, Takada H, Ihara K, Kawakami K, Yanai F, Takahata Y, Tanaka T, Kasuga N, Hara T:, Epstein-Barr virus (EBV) load and cytokine gene expression in activated T cells of chronic active EBV infection, J Infect Dis 183:1-7, 2001, 10.1086/317653, 183, 1, 1-7, 2001.01.|
|315.||Nomura A, Takada H, Jin C, Tanaka T, Ohga S, Hara T:, Functional analyses of cord blood natural killer cells and T cells. a distinctive interleukin-18 response, Exp Hematol 29:1169-1176, 2001, 10.1016/S0301-472X(01)00689-0, 29, 10, 1169-1176, 2001.01.|
|316.||Saito M, Ohga S, Endoh M, Nakayama H, Hara T, Yoshida S:, H2O2 nonproduction as a phenotype in Streptococcus pyogenes strains: its relation to stationary-phase survival and resistance to intracellular killing by granulocytes of chronic granulomatous disease patients, Microbiology 147:2469-2477, 2001, 2001.01.|
|317.||Takada H, Nomura A, Ohga S, Hara T:, IL-18 in hemophagocytic lymphohistiocytosis, Leuk & Lymphoma 42:21-28, 2001, 2001.01.|
|318.||Yamaguchi T, Ihara K, Matsumoto T, Tsutsumi Y, Nomura A, Ohga S, Hara T:, Inflammatory bowel disease-like colitis in glycogen storage disease type 1b, Inflamm Bowel Dis 7:128-132, 2001, 10.1097/00054725-200105000-00008, 7, 2, 128-132, 2001.01.|
|319.||Tokunaga Y, Ohga S, Suita S, Matsushima T, Hara T:, Moyamoya syndrome with spherocytosis: Effect of splenectomy on strokes, Pediatr Neurology 25:75-77, 2001, 10.1016/S0887-8994(01)00283-1, 25, 1, 75-77, 2001.01.|
|320.||Ohga S, Matsumoto N, Takada H, Nomura A, Matsuda T, Hara T:, Progressive vascular calcification in autoimmune polyglandular syndrome type I, Pediatric Radiology 31:213-214, 2001, 10.1007/s002470000403, 31, 3, 213-214, 2001.01.|
|321.||Ohga S, Kubo E, Nomura A, Takada H, Suga N, Ishii E, Suminoe A, Inamitsu T, Matsuzaki A, Kasuga N, Hara T:, Quantitative monitoring of circulating Epstein-Barr virus DNA for predicting the development of posttransplantation lymphoproliferative disease, Int J Haematol 73:323-326, 2001, 10.1007/BF02981956, 73, 3, 323-326, 2001.01.|
|322.||Ohga S, Kanaya Y, Maki H, Takada H, Ohshima K, Kanda M, Nomura A, Suminoe A, Matsuzaki A, Hara T:, Epstein-Barr virus-associated lymphoproliferative disease after a cord blood transplant for Diamond-Blackfan anemia, Bone Marrow Transplant 25:209-212, 2000, 10.1038/sj.bmt.1702138, 25, 2, 209-212, 2000.01.|
|323.||Ohga S, Ryu A, Nagatomo T, Takada H, Ihara K, Kawamoto K, Kai T, Hara T:, Inflammatory Bowel Disease in Anhidrotic Ectodermal Dysplasia: the lethal complication in two cases, Am J Gastroenterol 95:3651-3652, 2000, 2000.01.|
|324.||Kira R, Ohga S, Takada H, Gondo K, Mihara F, Hara T:, MR choroid plexus sign of iron overload in secondary hemochromatosis, Neurology 55:1340, 2000, 2000.01.|
|325.||Honda K, Ohga S, Takada H, Ohshima K, Kinukawa N, Nomura A, Hara T:, Neuron specific enolase in hemophagocytic lymphohistiocytosis: a potential indicator for macrophage activation?, Int J Hematol 72:55-60, 2000, 72, 1, 55-60, 2000.01.|
|326.||Mizuno Y, Takada H, Uragami K, Ihara K, Kira R, Suminoe A, Ohga S, Aoki T, Hara T:, Neurotropin-3 levels in cerebrospinal fluid from children with bacterial meningitis, viral meningitis, or encephalitis, J Child Neurol 15:19-21, 2000, 10.1177/088307380001500104, 15, 1, 19-21, 2000.01.|
|327.||Nomura A, Ohga S, Asaka Y, Takada H, Nakao F, Kusuhara K, Hara T:, Pneumocystis carinii pneumonia in Diamond-Blackfan anemia: the necessity of chemoprophylaxis for young infant, Int J Pediatr Hematol/Oncol 7:7-11, 2000, 7, 1, 7-11, 2000.01.|
|328.||Honda K, Takada H, Nagatoshi Y, Akazawa K, Ohga S, Ishii E, Okamura J, Hara T:, Thymus-independent expansion of T lymphocytes in children after allogeneic bone marrow transplantation, Bone Marrow Transplant 25:647-652, 2000, 10.1038/sj.bmt.1702198, 25, 6, 647-652, 2000.01.|
|329.||Ohshima K, Suzumiya J, Sugihara M, Nagafuchi S, Ohga S, Kikuchi M:, CD95 (Fas) ligand expression of Epstein-Barr virus (EBV)-infected lymphocytes: a possible mechanism of immune evasion in chronic active EBV infection, Pathol International 49:9-13, 1999, 10.1046/j.1440-1827.1999.00816.x, 49, 1, 9-13, 1999.01.|
|330.||Ohga S, Takada H, Honda K, Inamura T, Gondo K, Ohshima K, Yamamoto M, Hara T:, Central nervous system T-lymphoproliferative disorder in chronic active Epstein-Barr virus infection, J Pediatr Hematol/Oncol 21:42-46, 1999, 10.1097/00043426-199901000-00011, 21, 1, 42-46, 1999.01.|
|331.||Ohga S, Gondo K, Nomura A, Onoe Y, Matsuzaki A, Hara T:, Cerebrospinal fluid cytokine concentrations in a patient with lupus meningoencephalitis: differences from cytokine profiles in central nervous system infections, Br J Rheumatol 37:111-112, 1998, 37, 1, 111-112, 1999.01.|
|332.||Ohga S, Okada K, Ueda K, Takada H, Ohta M, Aoki T, Kinukawa N, Miyazaki S, Hara T:, Cerebrospinal fluid cytokine levels and dexamethasone therapy in bacterial meningitis, J Infect 39;55-60, 1999, 10.1016/S0163-4453(99)90103-2, 39, 1, 55-60, 1999.01.|
|333.||Takada H, Ohga S, Mizuno Y, Suminoe A, Matsuzaki A, Ihara K, Kinukawa N, Ohshima K, Kohno K, Kurimoto M, Hara T:, Oversecretion of interleukin-18 in hemophagocytic lymphohistiocytosis: a novel marker of disease activity, Br J Hematol 106:182-189, 1999, 10.1046/j.1365-2141.1999.01504.x, 106, 1, 182-189, 1999.01.|
|334.||Ohga S, Kimura N, Takada H, Nagano M, Ohshima K, Nomura A, Muraoka M, Take H, Yamamori S, Hara T:, Restricted diversification of T-cells in chronic active Epstein-Barr virus infection: Potential inclination to T-lymphoproliferative disease, Am J Hematol 61:26-33, 1999, 10.1002/(SICI)1096-8652(199905)61:1<26::AID-AJH6>3.0.CO;2-R, 61, 1, 26-33, 1999.01.|
|335.||Nagatomo T, Ohga S, Saito M, Takada H, Sasaki Y, Okada K, Inamura T, Hara T:, Streptococcus intermedius-brain abscess in chronic granulomatous disease, Eur J Pediatr 158:872-873, 1999, 10.1007/s004310051231, 158, 10, 872-873, 1999.01.|
|336.||Sakai Y, Nakayama H, Matsuzaki A, Nagatoshi Y, Suminoe A, Honda K, Inamitsu T, Ohga S, Hara T:, Trisomy 10 in a child with acute nonlymphocytic leukemia followed by relapse with a different clone, Cancer Genet Cytogenet 115:47-51, 1999, 10.1016/S0165-4608(99)00087-4, 115, 1, 47-51, 1999.01.|
|337.||Kajiwara M, Nonoyama S, Eguchi M, Morio T, Imai K, Okawa H, Kaneko M, Sako M, Ohga S, Maeda M, Hibi S, Hashimito H, Shibuya A, Ochs HD, Nakahata T, Yata J:, WASP is involved in proliferation and differentiation of human haematopoietic progenitors in vitro, Br J Haematol 107:254-262, 1999, 10.1046/j.1365-2141.1999.01694.x, 107, 2, 254-262, 1999.01.|
|338.||Watanabe I, Horiuchi T, Hatta N, Matsumoto M, Koike K, Kojima S, Ohga S, Fujita S:, Analysis of neurofibromatosis type 1 gene mutation in juvenile chronic myelogenous leukemia, Acta Hematologica 100:22-25, 1998, 10.1159/000040858, 100, 1, 22-25, 1998.01.|
|339.||Ishii E, Ohga S, Tanimura M, Mizutani S, Sako M, Imashuku S, Miyazaki S:, Clinical and epidemiological studies of familial erythrophagocytic lymphohistiocytosis in Japan, Med Pediatr Oncol 30:276-283, 1998, 10.1002/(SICI)1096-911X(199805)30:5<276::AID-MPO3>3.0.CO;2-C, 30, 5, 276-283, 1998.01.|
|340.||Ohshima K, Suzumiya J, Sugihara M, Nagafuchi S, Ohga S, Kikuchi M:, Clinicopathological study of severe chronic active Epstein-Barr virus infection that developed in association with lymphoproliferative disorder and/or hemophagocytic syndrome, Pathol International 48:934-943, 1998, 10.1111/j.1440-1827.1998.tb03864.x, 48, 12, 934-943, 1998.01.|
|341.||Sakai Y, Ohga S, Tonegawa Y, Takada H, Nakao F, Nakayama H, Aoki T, Yamamori S, Hara T:, Interferon-a therapy for chronic active Epstein-Barr virus infection : Potential effect on the development of T-lymphoproliferative disease, J Pediatr Hematol/Oncol 20:342-346, 1998, 10.1097/00043426-199807000-00013, 20, 4, 342-346, 1998.01.|
|342.||Kuroiwa M, Gondo H, Ashida K, Kamimura T, Miyamoto T, Niho Y, Tsukimori K, Nakano H, Ohga S:, Interferon-a therapy for chronic myelogenous leukemia during pregnancy, Am J Hematol 59:101-102, 1998, 10.1002/(SICI)1096-8652(199809)59:1<101::AID-AJH23>3.0.CO;2-D, 59, 1, 101-102, 1998.01.|
|343.||S Ohga, A Nomura, T Kai, A Matsuzaki, S Inaba, M Suda, K Ueda, Prolonged resolution of hemophagocytic lymphohistiocytosis following myeloablative chemotherapy and subsequent autologous peripheral blood stem cell transplantation, BONE MARROW TRANSPLANTATION, 19, 6, 633-635, 1997.03, A 30-month-old boy with hemophagocytic lymphohistiocytosis (HLH) received an autologous peripheral blood stem cell transplant (PBSCT) following high-dose chemotherapy. He presented with hemophagocytic syndrome (HPS) at 6 months of age, but relapsed despite the repeated administration of prednisolone, VP-16, cyclosporin A (CsA), and other cytotoxic agents, PBSC were obtained using combination chemotherapy with etoposide (VP16, 450 mg/m(2)), doxorubicin (70 mg/m(2)), vincristine (2 mg/m(2)) and cyclophosphamide (CY, 1200 mg/m(2)), 2.7 x 10(5)/kg CFU-GM PBSC were transplanted after similar high-dose VP16 preconditioning used for allogeneic BMT for HLH, The boy continues to remain in complete remission 30 months after PBSCT while receiving low-dose PSL/CsA therapy, High-dose chemotherapy followed by PBSCT may be an optional therapeutic approach for patients with HLH..|
|344.||Ishii E, Hara T, Ohga S, Ueda K, Suda M, Nakamura J, Yanagi T, Tsuji Y:, Familial erythrophagocytic lymphohistiocytosis: surface marker analysis using monoclonal antibodies, Eur J Haematol 38:63-66, 1987, 38, 1, 63-66, 1997.01.|
|345.||Ohga S, Nakao F, Narazaki O, Fusazaki N, Aoki T, Kamesaki K, Hara T:, Hypogammaglobulinemia in a patient with ring chromosome 21, Arch Dis Childh 77:252-254, 1997, 77, 3, 252-254, 1997.01.|
|346.||Ohga S, Miyazaki S:, Idiopathic pulmonary hemosiderosis: current diagnosis and management, Int J Pediatr Hematol/Oncol 4:161-170, 1997, 1997.01.|
|347.||Ohshima K, Suzumiya J, Ohga S, Ohgami A, Kikuchi M:, Integrated Epstein-Barr virus (EBV) and chromosomal abnormality in chronic active EBV infection, Int J Cancer 71:943-947, 1997, 1997.01.|
|348.||Ohga S, Ikeuchi K, Kadoya K, Okada K, Miyazaki C, Suita S, Ueda K:, Intrapulmonary Mycobacterium avium infection as the first manifestation of chronic granulomatous disease: a case report, J Infect 34:147-150, 1997, 10.1016/S0163-4453(97)92509-3, 34, 2, 147-150, 1997.01.|
|349.||Ohga S, Matsuzaki A, Kai T, Nomura A, Inaba S, Suda M, Ueda K:, Prolonged resolution of hemophagocytic lymphohistiocytosis after high dose chemotherapy followed by autologous peripheral blood stem cell transplantation, Bone Marrow Transplant 19:633-635, 1997, 10.1038/sj.bmt.1700702, 19, 6, 633-635, 1997.01.|
|350.||Ohga S, Kai T, Honda K, Nomura A, Inamitsu T, Ueda K:, What are the essential symptoms in the Hoyeraal Hreidarsson syndrome ?, Eur J Pediatr 156:80-81, 1997, 156, 1, 80-81, 1997.01.|
|351.||Nakayama H, Inamitsu T, Ohga S, Kai T, Suda M, Matsuzaki A, Ueda K:, Chronic myelomonocytic leukemia with t(8;9)(p11;q34) in childhood: an example of the 8p11 myeloproliferative disorder ?, Br J Haematol 92:692-695, 1996, 10.1046/j.1365-2141.1996.00386.x, 92, 3, 692-695, 1996.01.|
|352.||Nomura A, Ohga S, Matsuzaki A, Kai T, Suda M, Inaba S, Ueda K:, Granulocyte transfusion: stimulation of low dose granulocyte-colony stimulating factor in donors for leukapheresis, Acta Pediatr Jpn 38:317-321, 1996, 38, 4, 317-321, 1996.01.|
|353.||Kanno H, Fujii H, Hirono A, Ishida S, Ohga S, Fukumoto K, Matsuzawa K, Ogawa S, Miwa S:, Molecular analysis of glucose phosphate isomerase deficiency associated with hereditary hemolytic anemia, Blood 88:2321-2325, 1996, 88, 6, 2321-2325, 1996.01.|
|354.||Kamura T, Tsuda H, Yae Y, Hattori S, Ohga S, Shibata Y, Kawabata S, Hamasaki N:, An abnormal fibrinogen Fukuoka II (Bβ15Gly→Cys) characterized by defective fibrin lateral association and mixed disulfide formation, J Biol Chem 270:29392-29399, 1995, 270, 49, 29392-29399, 1995.01.|
|355.||Nakayama H, Kukita J, Ohga S, Ueda K:, Granulocyte-colony stimulating factor levels in cord blood and neonatal peripheral blood, Acta Paediatr Jpn 37:1-3, 1995, 1995.01.|
|356.||Ohga S, Higashi E, Nomura A, Matsuzaki A, Hirono A, Miwa S, Fujii H, Ueda K:, Haptoglobin therapy for acute favism: a Japanese boy with glucose-6-phosphate dehydrogenase Guadalajara, Br J Haematol 89:421-423, 1995, 10.1111/j.1365-2141.1995.tb03322.x, 89, 2, 421-423, 1995.01.|
|357.||Matsuzaki A, Kai T, Ohga S, Nomura A, Inaba S, Harada M, Ishii E, Ueda K:, Hematologic recovery after marrow-ablative chemotherapy and peripheral blood stem cell transplantation in children, Pediatr Hematol/Oncol 12:201-204, 1995, 10.3109/08880019509029556, 12, 2, 201-204, 1995.01.|
|358.||Nakayama H, Okamura J, Ohga S, Miyazaki C, Matsuzaki A, Ikuno Y, Ueda K, Tasaka H:, Herpes zoster in children with bone marrow transplantation: report from a single institution, Acta Paediatr Jpn 37:302-307, 1995, 1995.01.|
|359.||Ohga S, Ooshima A, Fukushige J, Ueda K:, Histiocytic hemophagocytosis in Kawasaki disease: changes in the hypercytokinemic state, Eur J Pediatr 154:539-541, 1995, 10.1007/BF02074830, 154, 7, 539-541, 1995.01.|
|360.||Ohga S, Takahashi K, Miyazaki S, Kato H, Ueda K:, Idiopathic pulmonary hemosiderosis in Japan: 39 possible cases from a survey questionnaire, Eur J Pediatr 154:994-998, 1995, 10.1007/BF01958645, 154, 12, 994-995, 1995.01.|
|361.||Ohga S, Okamura J, Nakayama H, Nagatoshi Y, Ueda K:, Interferon-gamma therapy for infection control in chronic granulomatous disease, Acta Paediatr Jpn 37:315-320, 1995, 1995.01.|
|362.||Ohga S, Okada K, Asahi T, Ueda K, Sakiyama Y, Matsumoto S:, Recurrent pneumococcal meningitis in a patient with transient IgG subclass deficiency, Acta Paediatr Jpn 37:196-200, 1995, 1995.01.|
|363.||Matsuzaki A, Okamura J, Nagatoshi Y, Kai T, Ohga S, Gondo H, Inaba S, Ueda K:, Treatment of young relapsed Hodgkin's disease patients with high-dose chemotherapy followed by peripheral blood stem cell transplantation, Leuk Lymphoma 18:503-509, 1995, 10.3109/10428199509059652, 18, 5-6, 505-509, 1995.01.|
|364.||Matsuzaki A, Inamitsu T, Watanabe T, Ohga S, Ishii E, Nagatoshi Y, Tasaka H, Suda M, Ueda K:, Acute promyelocytic leukemia in a patient treated with etoposide for Langerhans cell histiocytosis, Br J Haematol 86:887-889, 1994, 10.1111/j.1365-2141.1994.tb04851.x, 86, 4, 887-889, 1994.01.|
|365.||Ohga S, Nishizaki M, Nagashima T, Ueda K:, Association between serum interleukin-6 levels and fever in children with group A beta-hemolytic streptococcal infection, J Thermal Biol 19:91-96, 1994, 1994.01.|
|366.||Ohga S, Aoki T, Okada K, Akeda H, Fujioka K, Ohshima A, Mori T, Minamishima I, Ueda K:, Cerebrospinal fluid concentrations of interleukin-1β, tumor necrosis factor-α, and interferon-gamma in bacterial meningitis, Arch Dis Childh 70:123-125, 1994, 70, 2, 123-125, 1994.01.|
|367.||Iwata M, Nunoi H, Yamazaki H, Nakano T, Niwa H, Tsuruta S, Ohga S, Ohmi S, Kanegasaki S, Matsuda I:, Homologous dinucleotide (GT or TG) deletion in Japanese patients with chronic granulomatous disease with p47-phox deficiency, Bioch Bioph Res Commun 199:1372-1377, 1994, 10.1006/bbrc.1994.1382, 199, 3, 1372-1377, 1994.01.|
|368.||Matsuzaki A, Ohga S, Ueda K, Okamura S:, Induction of CD33-positive blasts by granulocyte colony-stimulating factor in a child with common acute lymphoblastic leukemia, Int J Pediatr Hematol/Oncol 1:339-341, 1994, 1994.01.|
|369.||Ohga S, Nomura A, Suga N, Hikino S, Kira R, Matsuzaki A, Masuda K, Ueda K:, Liposteroid against refractory pulmonary hemorrhage in idiopathic pulmonary hemosiderosis, Eur J Pediatr 153:687-690, 1994, 10.1007/BF02190693, 153, 9, 687-690, 1994.01.|
|370.||Wakamatsu C, Ichinose M, Manabe J, Fucharoen S, Sawada H, Ohga S, Nishimura J, Nukina H, Harada T, Shirahata S, Moriwaki Y, Uike N, Kozuru M, Ohi N, Mineta M, Nomiyama M, Fukumaki Y:, Molecular basis ofβ-thelassemia in Japan: heterogeneity and origins of mutation, Wakamatsu C, Ichinose M, Manabe J, Fucharoen S, Sawada H, Ohga S, Nishimura Acta Haematol 91:136-143, 1994, 1994.01.|
|371.||Yamashita H, Kukita J, Ohga S, Nakayama H, Akazawa K, Ueda K:, Serum erythropoietin levels in term and preterm infants during the first year of life, Am J Pediatr Hematol/Oncol 16:213-218, 1994, 16, 3, 213-218, 1994.01.|
|372.||Ohga S, Nagashima T, Nishizaki M, Hirabaru C, Inoue T, Ise K, Hara T, Ueda K:, Severe aplastic anemia in a patient with primary immunodeficiency, Acta Paediatr Jpn 36:212-216, 1994, 1994.01.|
|373.||GUILAN, X, Y KISHIMOTO, M DATE, T KATSURADA, Y YAMAMOTO, H TANIGUCHI, K HAMAMOTO, T NAGANO, S OHGA, H KITAJIMA, M FUJIMOTO, T KIMURA, H FUJITAKE, ULTRASTRUCTURAL-LOCALIZATION OF MYELOPEROXIDASE ACTIVITY IN ACUTE MONOBLASTIC LEUKEMIA, INTERNATIONAL JOURNAL OF HEMATOLOGY, 59, 1, 17-23, 1993.12, In five patients with acute monoblastic leukemia (AMoL), the ultrastructural localization of myeloperoxidase (MPO) activity was investigated by two methods, one generally used for the detection of MPO and the other for the detection of platelet peroxidase. The MPO-positive rate achieved was lower with the former method than with the latter, indicating that MPO is degraded during the fixation of AMoL cells for electron microscopy. If the ultrastructural MPO positivity of leukemic cells varies when different detection methods are used, the possibility of monocytic leukemia should be considered..|
|374.||Ohga S, Saito M, Matsuzaki A, Kai T, Ueda K:, Disseminated intravascular coagulation in a patient with hemophilia B during Factor IX replacement therapy, Br J Hematol 84:343-345, 1993, 10.1111/j.1365-2141.1993.tb03078.x, 84, 2, 343-345, 1993.01.|
|375.||Shimoda K, Okamura S, Takamatsu Y, Inaba S, Okamura T, Ohga S, Ueda K, Niho Y:, Granulocyte colony-stimulating factor and platelet aggregation, Lancet 341:633, 1993, 10.1016/0140-6736(93)90394-V, 341, 8845, 633-633, 1993.01.|
|376.||Ohga S, Matsuzaki A, Nishizaki M, Nagashima T, Kai T, Suda M, Ueda K:, Inflammatory cytokines in virus-associated hemophagocytic syndrome: interferon-gamma as a sensitive indicator of disease activity, Am J Pediatr Hematol/Oncol 15:291-298, 1993, 15, 3, 291-298, 1993.01.|
|377.||Hara T, Matsumoto T, Mizuno Y, Nishizaki M, Ueda K, Motooka M, Kimura N, Oshimi K, Ohga S, Yoshikai Y:, Peripheral expansion of gd T cell receptor-positive cells in a patient with Crohn's disease, Acta Paediatr Jpn 35:45-48, 1993, 1993.01.|
|378.||Minamishima I, Ohga S, Ishii E, Matsuzaki A, Kai T, Akazawa K, Ueda K:, Serum interleukin-6 and fever at diagnosis in children with acute leukemia, Am J Pediatr Hematol/Oncol 15:239-244, 1993, 15, 2, 239-244, 1993.01.|
|379.||Inaba S, Takamatsu Y, Yamamoto A, Shimoda K, Fukuda T, Ohga S, Hamaguchi K, Ueda K:, The use of recombinant granulocyte-colony-stimulating factor for granulocyte harvest, Transfusion 32:690-691, 1993, 10.1046/j.1537-2995.1992.32792391049.x, 32, 7, 690-691, 1993.01.|
|380.||Hiromatsu K, Yoshikai Y, Matsuzaki G, Ohga S, Muramori K, Matsumoto K, Bluestone JA, Nomoto K:, A protective role of gd T cells in primary infection with Listeria monocytogenes in mice, J Exp Med 175:49-56, 1992, 10.1084/jem.175.1.49, 175, 1, 49-56, 1992.01.|
|381.||Ohga S, Okada K, Mitsui K, Aoki T, Ueda K:, Outbreaks of group A beta-hemolytic streptococcal pharyngitis in children: correlation of serotype T4 with scarlet fever, Scand J Infect Dis 24:599-605, 1992, 10.3109/00365549209054645, 24, 5, 599-605, 1992.01.|
|382.||Ohga S, Miyazaki C, Okada K, Akazawa K, Ueda K:, The inflammatory cytokines in measles: correlation between serum interferon-g levels and lymphocyte subpopulation, Eur J Pediatr 151:492-496, 1992, 10.1007/BF01957751, 151, 7, 492-496, 1992.01.|
|383.||Ohga S, Okada K, Miyazaki C, Akazawa K, Ueda K:, The measles outbreak in Chikuhou-district, Fukuoka Japan 1990: correlation between herd immunity level and outbreak size, Acta Paediatr Jpn 34:447-453, 1992, 1992.01.|
|384.||S NOMURA, H NAGATA, M SUZUKI, K KONDO, S OHGA, T KAWAKATSU, H KIDO, T FUKUROI, K YAMAGUCHI, K IWATA, M YANABU, T SOGA, T KOKAWA, K YASUNAGA, MICROPARTICLE GENERATION DURING INVITRO PLATELET ACTIVATION BY ANTI-CD9 MURINE MONOCLONAL-ANTIBODIES, THROMBOSIS RESEARCH, 62, 5, 429-439, 1991.06, We used flow cytometry and two anti-CD9 murine monoclonal antibodies (NNKY1-19, MALL13) to investigate the glycoprotein composition and the potential functions of microparticles (MP) released by platelets exposed to these antibodies in vitro. NNKY1-19 produced aggregation with characteristics similar to those noted in previous reports. The action of MALL13 on platelets in platelet-rich plasma (PRP), however, differs from that of other anti-CD9 antibodies. The normal fluctuation in the MALL13-induced change in optical density disappeared when complement was present. MALL13-induced effect for platelet in PRP was not inhibited by preincubation with monoclonal anti-GPIIb/IIIa antibody, but was inhibited in washed platelets (WP). Furthermore, following MALL13 stimulation in PRP platelets, the amount of buffer LDH markedly increased and electron microscopy findings showed vacuoles appearing inside the platelets. These results suggest that MALL13 has at least two effects on platelets that differ for PRP platelets and WP. The number of MP released was increased by the addition of anti-CD9 antibodies. MP surfaces were found to be rich in CD9 protein. MALL13 stimulation lead to a significant increase in the binding of C1q and C3 to platelets and caused the production of MP to occur more rapidly than it did the exposure of fibrinogen binding sites in the presence of complement. The analysis of the relationship of MP to anti-CD9 monoclonal antibody may be useful in the investigation of the relationship between platelet function and coagulation regulation..|
|385.||Minamishima I, Ohga S, Ishii E, Miyazaki C, Hamada K, Akazawa K, Ueda K:, Aseptic meningitis in children: correlation between fever and interferon-gamma level, Eur J Pediatr 150:722-725, 1991, 10.1007/BF01958764, 150, 10, 722-725, 1991.01.|
|386.||Ohga S, Ueda K, Yoshikai Y, Takeda K, Hiromatsu K, Nomoto K:, Kinetics of fever and its related cytokines in mice after intraperitoneal infection with Listeria monocytogenes, J Thermal Biol 16:103-107, 1991, 10.1016/0306-4565(91)90006-N, 16, 2, 103-107, 1991.01.|
|387.||Ishii E, Ohga S, Aoki T, Yamada S, Sako M, Tasaka H, Kuwano A, Sasaki M, Ueda K:, Prognosis of virus-associated hemophagocytic syndrome and malignant histiocytosis in children: correlation with serum interleukin-1 and tumor necrosis factor activity, Acta Haematol 85:93-99, 1991, 1991.01.|
|388.||Ishii E, Ohga S, Ueda K, Akazawa K:, Serum interleukin-1 and tumor necrosis factor activities in febrile children with acute leukemia, Int J Hematol 54:79-84, 1991, 54, 1, 79-84, 1991.01.|
|389.||Ishii E, Ohga S, Murao I, Kobayashi M, Kimura K, Eguchi H, Akazawa K, Ueda K:, Tumor necrosis factor in the cerebrospinal fluid of children with central nervous system leukemia, Leuk Res 15:143-147, 1991, 10.1016/0145-2126(91)90095-B, 15, 2-3, 143-147, 1991.01.|
|390.||Takeda Y, Yoshikai Y, Ohga S, Nomoto K:, Augmentation of host defense against bacterial infection pretreated intraperitonealy with an alpha-glucan RBS in mice, Immunopharmacol Immunotoxicol 12:457-477, 1990, 10.3109/08923979009006473, 12, 3, 457-477, 1990.01.|
|391.||Ogimoto M, Yoshikai Y, Matsuzaki G, Ohga S, Nomoto K:, Clonal deletion of self-Mls-reactive thymocytes at the early stage in H-2 compatible but Mls-disparate radiation chimeras, Immunol 69:482-486, 1990, 69, 3, 482-486, 1990.01.|
|392.||Ogimoto M, Yoshikai Y, Matsuzaki G, Ohga S, Nomoto K:, Deletion of self-reactive T cells in the donor-derived-T cells but not in the host-derived T cells in allogeneic radiation chimeras, Thymus 17:11-22, 1991, 17, 1, 11-22, 1990.01.|
|393.||Ohga S, Yoshikai Y, Kishihara K, Matsuzaki G, Ogimoto M, Nomoto K:, Different expression of T-cell receptor b-chain variable region genes in lymph nodes of lpr mice with different alleles of major histocompatibility complex, Immunol 70:216-222, 1990, 70, 2, 216-222, 1990.01.|
|394.||Yoshikai Y, Ohga S, Takeda Y, Nomoto K:, Effects of stimulated or immunologically activated macrophages on the induction of immune responses to Listeria monocytogenes, Immunobiol 180:124-137, 1990, 180, 2-3, 124-137, 1990.01.|
|395.||Hara T, Mizuno Y, Nagata M, Okabe Y, Taniguchi S, Harada M, Niho Y, Oshimi K, Ohga S, Yoshikai Y, Nomoto K, Yumura K, Kawa-Ha K, Ueda K:, Human gamma/delta T cell receptor-positive cell-mediated inhibition of erythropoiesis in vitro in a patient with type I autoimmune polyglandular syndrome and pure red cell aplasia, Blood 75:941-950, 1990, 75, 4, 941-950, 1990.01.|
|396.||Ohga S, Yoshikai Y, Takeda Y, Hiromatsu K, Nomoto K:, Sequential appearance of T cell receptor g/d and a/b-bearing T cells in the peritoneal cavity during an intraperitoneal infection with Listeria monocytogenes, Eur J Immunol 20:533-538, 1990, 1990.01.|
|397.||Ishii E, Ohga S, Ueda K:, Tumor necrosis factor and fever at initial diagnosis in children with solid tumors, Pediatr Hematol Oncol 7:253-257, 1990, 10.3109/08880019009033400, 7, 3, 253-257, 1990.01.|
|398.||Ohga S, Yoshikai Y, Kishihara K, Matsuzaki G, Nomoto K:, Abnormal rearrangements of T-cell receptor genes occur in long-term cultured bone marrow cells of lpr/lpr mice, Immunol 67:543-546, 1989, 67, 4, 543-546, 1989.01.|
|399.||Ohga S, Yoshikai Y, Kishihara K, Matsuzaki G, Asano T, Nomoto K:, Expression and sequences of T cell receptor b-chain variable genes in the enlarged lymph nodes of C57BL/6-lpr/lpr mice, Clin Exp Immunol 77:130-136, 1989, 77, 1, 130-136, 1989.01.|
|400.||Yoshikai Y, Takeda Y, Ohga S, Kishihara K, Matsuzaki G, Nomoto K:, Rearrangements of T cell antigen receptor g and d chain genes are detected in the long-term cultured bone marrow cells of athymic nude mice but not in those of euthymic mice, Immunol 66:512-516, 1989, 66, 4, 512-516, 1989.01.|
|401.||Yoshikai Y, Matsuzaki G, Takeda Y, Ohga S, Kishihara K, Yuuki H, Nomoto K:, Functional T cell receptor delta chain gene messages in athymic nude mice, Eur J Immunol 18:1039-1043, 1988, 10.1002/eji.1830180711, 18, 7, 1039-1043, 1988.01.|
|402.||Ohga S, Kajiwara M, Toubo Y, Takeuchi T, Ohtsuka M, Sano M, Ishii E, Ueda K:, Neonatal hemophilia B with intracranial hemorrhage: case report, Am J Pediatr Hematol/Oncolol 10:244-248, 1988, 10, 3, 244-248, 1988.01.|
|403.||Ohga S, Ishii E, Fujioka K, Ueda K:, Inversion of chromosome 16 with abnormal marrow eosinophils in acute myelomonocytic leukemia: a case report of 9-month-old infant, Ohga S, Ishii E, Fujioka K, Ueda K: Acta Hematol Jpn 50:114-118, 1987, 50, 1, 114-118, 1987.01.|