|Shouichi Ohga||Last modified date：2019.06.19|
Professor / Department of Clinical Medicine / Faculty of Medical Sciences
|Shouichi Ohga||Last modified date：2019.06.19|
|1.||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 In Japan, however, the active recommendation of JE vaccine was retracted in 2005 because of the potential risk of acute disseminated encephalomyelitis.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..
|2.||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..|
|3.||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.|
|4.||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..
|5.||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..|
|6.||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.|
|7.||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..|
|8.||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.|
|9.||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..
|10.||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..|
|11.||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..|
|12.||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..
|13.||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..|
|14.||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..|
|15.||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..|
|16.||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..|
|17.||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..
|18.||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..|
|19.||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..
|20.||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..|
|21.||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..|
|22.||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..
|23.||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..|
|24.||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..|
|25.||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..
|26.||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..
|27.||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..|
|28.||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..|
|29.||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..|
|30.||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..|
|31.||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..|
|32.||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.|
|33.||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..|
|34.||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..
|35.||, 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..|
|36.||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..|
|37.||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..|
|38.||, 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..|
|39.||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..|
|40.||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.
|41.||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..|
|42.||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..|
|43.||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..|
|44.||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...|
|45.||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..|
|46.||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..|
|47.||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.|
|48.||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.|
|49.||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..|
|50.||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.|
|51.||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.|
|52.||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.|
|53.||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.|
|54.||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。.|
|55.||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.|
|56.||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.|
|57.||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.|
|58.||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.
|59.||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.
|60.||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.|
|61.||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.
|62.||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.
|63.||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.|
|64.||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.|
|65.||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.|
|66.||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.|
|67.||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.|
|68.||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.|
|69.||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.|
|70.||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.|
|71.||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.|
|72.||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.|
|73.||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.|
|74.||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.|
|75.||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.|
|76.||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.|
|77.||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.|
|78.||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.|
|79.||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.|
|80.||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.|
|81.||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.|
|82.||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.|
|83.||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.|
|84.||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.|
|85.||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.|
|86.||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.
|87.||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.
|88.||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.
|89.||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
|90.||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.|
|91.||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.
|92.||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.
|93.||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.
|94.||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.
|95.||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.
|96.||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.
|97.||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.
|98.||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.
|99.||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.|
|100.||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.|
|101.||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.|
|102.||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.|
|103.||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.|
|104.||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.|
|105.||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.|
|106.||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.|
|107.||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.|
|108.||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.|
|109.||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.|
|110.||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.|
|111.||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.|
|112.||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.|
|113.||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.|
|114.||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.|
|115.||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.|
|116.||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.|
|117.||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.|
|118.||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.|
|119.||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.|
|120.||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.|
|121.||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.|
|122.||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.|
|123.||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.|
|124.||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.|
|125.||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.|
|126.||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.|
|127.||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.|
|128.||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.|
|129.||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.|
|130.||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.|
|131.||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.|
|132.||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.|
|133.||Takada H, Nomura A, Ohga S, Hara T:, IL-18 in hemophagocytic lymphohistiocytosis, Leuk & Lymphoma 42:21-28, 2001, 2001.01.|
|134.||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.|
|135.||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.|
|136.||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.|
|137.||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.|
|138.||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.|
|139.||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.|
|140.||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.|
|141.||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.|
|142.||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.|
|143.||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.|
|144.||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.|
|145.||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.|
|146.||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.|
|147.||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.|
|148.||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.|
|149.||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.|
|150.||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.|
|151.||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.|
|152.||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.|
|153.||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.|
|154.||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.|
|155.||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.|
|156.||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.|
|157.||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.|
|158.||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.|
|159.||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.|
|160.||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.|
|161.||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.|
|162.||Ohga S, Miyazaki S:, Idiopathic pulmonary hemosiderosis: current diagnosis and management, Int J Pediatr Hematol/Oncol 4:161-170, 1997, 1997.01.|
|163.||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.|
|164.||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.|
|165.||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.|
|166.||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.|
|167.||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.|
|168.||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.|
|169.||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.|
|170.||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.|
|171.||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.|
|172.||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.|
|173.||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.|
|174.||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.|
|175.||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.|
|176.||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.|
|177.||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.|
|178.||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.|
|179.||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.|
|180.||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.|
|181.||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.|
|182.||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.|
|183.||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.|
|184.||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.|
|185.||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.|
|186.||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.|
|187.||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.|
|188.||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.|
|189.||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.|
|190.||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.|
|191.||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.|
|192.||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.|
|193.||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.|
|194.||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.|
|195.||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.|
|196.||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.|
|197.||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.|
|198.||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.|
|199.||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.|
|200.||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.|
|201.||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.|
|202.||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.|
|203.||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.|
|204.||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.|
|205.||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.|
|206.||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.|
|207.||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.|
|208.||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.|
|209.||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.|
|210.||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.|
|211.||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.|
|212.||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.|
|213.||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.|
|214.||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.|
|215.||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.|