記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Annals of Allergy, Asthma and Immunology  

DOI： 10.1016/j.anai.2023.10.013

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical and Translational Immunology  

Objectives: The objectives of this study were to investigate the pathophysiology of Kawasaki disease (KD) from immunological and oxidative stress perspectives, and to identify real-time biomarkers linked to innate immunity and oxidative stress in KD. Methods: We prospectively enrolled 85 patients with KD and 135 patients with diverse conditions including immune, infectious and non-infectious diseases for this investigation. Flow cytometry was used to analyse the surface expression of CD14, CD38 and CD62L on monocytes, along with a quantitative assessment of CD14 down-modulation. Additionally, oxidative stress levels were evaluated using derivatives of reactive oxygen metabolites (d-ROMs) and antioxidant capacity measured by a free radical elective evaluator system. Results: During the acute phase of KD, we observed a prominent CD14 down-modulation on monocytes, reflecting the indirect detection of circulating innate immune molecular patterns. Moreover, patients with KD showed a significantly higher CD14 down-modulation compared with infectious and non-infectious disease controls. Notably, the surface expression of CD14 on monocytes was restored concurrently with responses to intravenous immunoglobulin and infliximab treatment in KD. Furthermore, d-ROM levels in patients with KD were significantly elevated compared with patients with infectious and non-infectious diseases. Following intravenous immunoglobulin treatment, oxidative stress levels decreased in patients with KD. Conclusion: Monitoring CD14 down-modulation on monocytes in real-time is a valuable strategy for assessing treatment response, distinguishing KD relapse from concomitant infections and selecting second-line therapy after IVIG treatment in KD patients. The interplay between inflammation and oxidative stress likely plays a crucial role in the development of KD.

DOI： 10.1002/cti2.1482

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pediatric Infectious Disease Journal  

DOI： 10.1097/INF.0000000000004230

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Early Human Development  

INTRODUCTION: To establish actionable neonatal screening during the first month of life, we investigated critical diseases in seemingly healthy newborns discharged from birth hospitals. METHODS: This retrospective study enrolled previously healthy full-term infants who visited our hospital, a tertiary hospital in Japan, from home between 5 and 28 days after birth from 2009 to 2018. Infants with known perinatal or congenital diseases, positive newborn screening results, or accidental injuries were excluded. Data were collected from electronic medical records, including principal diagnosis, clinical details, and prognosis at 18 months of age. RESULTS: Ninety-seven (58 %) of 168 eligible neonates were admitted to the hospital, and 71 (42 %) were not. The median admission rate in patients with disease onset at ≤14 days after birth (80 %) was significantly higher than that in patients with disease onset at ≥15 days (42 %). Among 45 patients who received intensive medical care, 5 died and 10 developed neurodevelopmental sequelae. Four of 5 patients died by 100 days. Among 25 diseases treated in intensive care unit, 17 (68 %) diseases had a prevalence of <1 per 2000 live births. The commonly used diagnostic methods were imaging (n = 58, 35 %) and physical examination (n = 34, 20 %). CONCLUSION: Critical diseases due to rare and heterogeneous causes in ostensibly healthy newborns occurred predominantly in the first two weeks of life. Optimal newborn screening and health check-up protocols may benefit from the wide spectrum of life-threatening diseases occurring in home after birth.

DOI： 10.1016/j.earlhumdev.2023.105869

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Haematologica  

Non-tuberculous mycobacterial infection (NTM) is rare in healthy children, with lymphadenitis being the most common presentation. Immunocompromised populations are known to be at high risk, but the clinical picture of NTM infection in pediatric hematology/oncology patients is unclear. In this nationwide retrospective analysis of patients under the age of 40 treated in Japanese pediatric hematology/oncology departments who developed NTM infection between January 2010 and December 2020, 36 patients (21 patients with hematopoietic stem cell transplantation (HSCT) and 15 nontransplant patients) were identified. Post-transplant patients were infected with NTM at 24 sites, including the lungs (n = 12), skin and soft tissues (n = 6), bloodstream (n = 4), and others (n = 2). Nine of twelve patients with pulmonary NTM infection had a history of pulmonary graft-versus-host disease (GVHD), and rapid-growing mycobacteria (RGM) were isolated from five of them. In nontransplant patients, the primary diseases were acute lymphoblastic leukemia (ALL; n = 5), inborn errors of immunity (IEI; n = 6), and others (n = 4). All cases of ALL had bloodstream infections with RGM, whereas all cases of IEI were infected with slow-growing mycobacteria (SGM). In summary, three typical clinical scenarios for pediatric hematology/oncology patients have been established: RGM-induced pulmonary disease in patients with pulmonary GVHD, RGM bloodstream infection in patients with ALL, and SGM infection in patients with IEI. Our findings suggest that NTM must be regarded as a pathogen for infections in these high-risk patients, especially those with pulmonary GVHD, who may require active screening for NTM.

DOI： 10.3324/haematol.2023.283636

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Clinical Immunology  

Microglia play versatile roles in progression of and protection against neuroinflammatory diseases. Little is known, however, about the mechanisms underlying the diverse reactivity of microglia to inflammatory conditions. We investigated how human induced microglia-like (iMG) cells respond to innate immune ligands. Quantitative PCR showed that poly-I:C and lipopolysaccharide (LPS) activated the expression of IL1B and TNF. Immunoreactivity of iMG did not differ between controls (n = 11) and patients with neuroinflammatory diseases (n = 24). Flow cytometry revealed that CD14high cells expressed interleukin (IL) -1β after LPS treatment. Immunoblotting showed that poly-I:C and LPS differentially activated inflammatory pathways but commonly induced mitochondrial instability and the expression of pyruvate kinase isoform M2 (PKM2). Furthermore, a potent stimulator of PKM2 (DASA-58) alleviated IL-1β production after LPS treatment. These data indicate that heterogeneous cell populations and mitochondrial stability underlie the divergent immunoreactivity of human iMG in environments.

DOI： 10.1016/j.clim.2023.109756

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記述言語：英語   出版者・発行元：エルゼビア・ジャパン(株)  

マウスの生後早期の視床機能の発達におけるShank3a/bアイソフォームの役割について検討した。WTマウスとShank3a/bノックアウトを使用した。評価項目は脳の各領域における定量PCR、カイニン酸治療、免疫蛍光染色、ウェスタンブロット法などとした。その結果、マウスShank3スプライシングアイソフォームShank3a/bは視床核で特異的に発現し、生後2～4週間でピークに達することが示された。また、Shank3a/bノックアウトマウスでは視床核のパルブアルブミンが低かった。一貫して、Shank3a/bノックアウトマウスは、カイニン酸処理後、WTマウスと比較して全般発作を起こしやすいことが示された。以上から、Shank3a/bのNT-Ankドメインは、マウス生後早期において、視床皮質ニューロンを過剰興奮から守る分子経路を制御していることが示された。

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Neuroscience Research  

Epileptic seizures are distinct but frequent comorbidities in children with autism spectrum disorder (ASD). The hyperexcitability of cortical and subcortical neurons appears to be involved in both phenotypes. However, little information is available concerning which genes are involved and how they regulate the excitability of the thalamocortical network. In this study, we investigate whether an ASD-associated gene, SH3 and multiple ankyrin repeat domains 3 (Shank3), plays a unique role in the postnatal development of thalamocortical neurons. We herein report that Shank3a/b, the splicing isoforms of mouse Shank3, were uniquely expressed in the thalamic nuclei, peaking from two to four weeks after birth. Shank3a/b-knockout mice showed lower parvalbumin signals in the thalamic nuclei. Consistently, Shank3a/b-knockout mice were more susceptible to generalized seizures than wild-type mice after kainic acid treatments. Together, these data indicate that NT-Ank domain of Shank3a/b regulates molecular pathways that protect thalamocortical neurons from hyperexcitability during the early postnatal period of mice.

DOI： 10.1016/j.neures.2023.03.001

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記述言語：英語   出版者・発行元：エルゼビア・ジャパン(株)  

症例は12歳男児で、慢性肉芽腫性疾患の治癒を目的とした臍帯血移植を受けるために当院に入院した。ブスルファンとフルダラビンの移植前処置後に臍帯血を用いた同種造血幹細胞移植を施行した。移植後4日目から発熱性好中球減少症を発症し、23日目に胸痛を発症した。移植前に明らかな感染症はなかった。画像診断で播種性肺膿瘍および脳膿瘍が認められた。ボリコナゾール投与を行い、生着後、症状は改善した。ボリコナゾールの慢性投与により、脳膿瘍の治療効果も良好であった。患者の吐き出した菌球の一部を培養したところ、糸状菌が発生した。28S rRNA遺伝子の解析によりSchizophyllum commune(スエヒロタケ)を同定した。カタラーゼテストはS.communeに陽性であり、S.communeが本症例に病原性を有することが示された。S.communeに対する特異的IgGの評価から、定着は否定されなかったが、移植での周術期感染が示唆された。

記述言語：英語  

INTRODUCTION: Williamsia muralis is an environmental bacterium first detected in 1999. Infections with W. muralis isolated have been reported in two elderly patients, and were associated with the surgical intervention of artificial objects. We present a case of bacteraemia caused by W. muralis following haematopoietic cell transplantation (HCT). CASE PRESENTATION: A 10-year-old Japanese boy presented with fever and the swelling of the left cheek 8 days after HCT for the treatment of Fanconi anaemia. Gram-positive, rod-shaped bacteria were isolated from the blood cultures after 5 days incubation. 16S rRNA sequencing, but not mass spectrometry, identified a strain of W. muralis (1 414 bp, %ID 100 %). The phlegmon did not respond to antimicrobial therapy, but remitted with defervescence after a successful engraftment with teicoplanin and meropenem therapy on day 16 after HCT. The patient experienced recurrence of the bacteraemia, leading to central venous catheter (CVC) line removal. The same strain of W. muralis was isolated from the cultured tip of the CVC. To our knowledge, this is the first reported case of W. muralis bacteraemia and was complicated by CVC infection after HCT. CONCLUSION: W. muralis bacteraemia developed in an immunocompromised child. Introduction of artificial objects into the body raises a risk of rare infection with slowly growing environmental bacteria.

DOI： 10.1099/acmi.0.000679.v3

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記述言語：日本語  

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記述言語：日本語   出版者・発行元：(一社)日本小児感染症学会  

アメーバ赤痢はEntamoeba histolyticaによる感染症で,血便を呈する疾患の一つである.主に途上国で不衛生による水系感染をきたすが,日本では海外渡航歴のないアメーバ赤痢の小児例はまれである.今回われわれは,持続する血便を呈し,診断確定までに1年間要した海外渡航歴のないアメーバ赤痢の1歳児例を経験したので報告する.症例は1歳5ヵ月から鮮血便が持続し,便培養で有意菌は検出されなかった.下部消化管内視鏡で上行結腸から直腸に連続するリンパ濾胞様の隆起と多発するアフタ様びらんおよび潰瘍を認めた.食物蛋白誘発胃腸炎,超早期発症型炎症性腸疾患などを念頭に精査を進めたが診断に至らなかった.他に随伴症状はなく全身状態良好であったが,血便は持続し,貧血と低ガンマグロブリン血症を合併した.発症1年後に再検した下部消化管の生検病理でアメーバ赤痢と診断し,メトロニダゾール内服が奏効した.海外渡航歴や家族内感染はなく,感染経路は特定できなかった.アメーバ赤痢は日本人の乳幼児にはまれであり,診断に有用な検査は容易ではなく保険収載の問題もあり診断に難渋した.(著者抄録)

記述言語：英語   出版者・発行元：Journal of Infection and Chemotherapy  

Schizophyllum commune is a widely distributed basidiomycete fungus that occasionally causes sinusitis or allergic bronchopulmonary mycosis. The invasive infection mostly occurs in immunocompromised adults. The number of reports on S. commune infection have increased in this decade due to the expansion of diagnostic techniques and awareness in clinical practice. However, S.commune infection in patients with primary immunodeficiencies has not been reported yet. Here, we described S. commune-abscesses developed in the brain and lung of a boy with chronic granulomatous disease (CGD) after allogenic hematopoietic cell transplantation (HCT). A 12-year-old CGD patient developed febrile neutropenia from day 4 after HCT, followed by chest pain on day 23. He had no obvious infection before HCT. Diagnostic imaging revealed disseminated lung and brain abscesses. He received administration of voriconazole, and his symptoms improved after engraftment. Chronic administration of voriconazole had also a favorable therapeutic response to brain lesion. A part of the fungus ball exhaled by the patient was cultured to develop a filamentous fungus. S. commune was identified by the analysis of the 28S rRNA gene. The catalase test was positive for S. commune, indicating that S. commune had virulence in this patient with CGD. The assessment of specific-IgG to S. commune suggested peri-transplant infection, although colonization was not excluded. This rare pediatric case of S. commune infection highlights that CGD patients are vulnerable to invasive infection, especially when undergoing HCT.

DOI： 10.1016/j.jiac.2022.10.015

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記述言語：英語   出版者・発行元：Pediatric Allergy and Immunology  

DOI： 10.1111/pai.13686

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記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Pediatrics International  

BACKGROUND: In November 2011, rotavirus (RV) vaccine was launched in Japan as a voluntary vaccination to prevent RV-associated gastroenterocolitis. We examined the characteristics of intussusception following RV vaccination in our two centers. METHODS: We investigated intussusception patients <16 years old from January 2006 to September 2020. Patients were categorized according to the period (before [Group A] or after the introduction of arbitrary RV vaccination [Group B]). The patient characteristics and treatment of intussusception were retrospectively investigated. RESULTS: During the study period, 560 patients (group A, n = 233; group B, n = 327) were identified. The distribution of patients who were 0-6 months old was not significantly different between the groups (group A, n = 12, 5.2%; group B, n = 18, 5.5%). Among these 18 patients in Group B, 7 were vaccinated against RV, and 10 were not. One patient was excluded due to incomplete data. On comparing patients with and without RV vaccination, the mean age at the onset of intussusception was 3.3 ± 0.4 versus 4.0 ± 0.3 months (P = 0.19), the mean interval from the onset to treatment was 7.5 ± 2.4 versus 16.0 ± 2.2 h (P = 0.03), the time of the contrast enema for treatment was 9.1 ± 3.3 versus 7.7 ± 2.8 min (P = 0.76), and the final pressure of the contrast enema was 92.5 ± 4.4 versus 92.2 ± 4.4 cmH2 O (P = 0.97). CONCLUSIONS: Arbitrary RV vaccination did not influence the age distribution of intussusception, and the interval from the onset to treatment was significantly shorter in the patients with RV vaccination than in those without it. Recognizing the presence of intussusception following RV vaccination enables accurate treatment.

DOI： 10.1111/ped.15332

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記述言語：英語   出版者・発行元：John Wiley & Sons Australia, Ltd  

ロタウイルス(RV)ワクチン接種と腸重積症の関連を評価するため、RVワクチン任意接種導入後の腸重積症の発生率と特徴について検討した。2006年1月～2020年9月に2施設において腸重積症と診断された16歳未満の患児560例を、診断時期によりRVワクチン任意接種導入前(233例、グループA)と導入後(327例、グループB)へ分類した。早期発症型(生後6ヵ月未満)の患児はグループA 12例(5.2%)、グループB 18例(5.5%)と有意差はなく、RVワクチン任意接種は腸重積症の年齢分布に影響を及ぼさないことが示された。グループBの早期発症型患児18例のうち、データが不完全であった1例を除外し、RVワクチン接種を行った7例と行わなかった10例を比較した。その結果、腸重積症発症時の平均月齢はそれぞれ3.3±0.4ヵ月、4.0±0.3ヵ月(P=0.19)、発症から治療までの平均時間はそれぞれ7.5±2.4時間、16.0±2.2時間とワクチン接種例で有意に短く(P=0.03)、注腸整復の所要時間はそれぞれ9.1±3.3分、7.7±2.8分(P=0.76)、整復圧はそれぞれ92.5±4.4cmH2O、92.2±4.4cmH2O(P=0.97)であった。

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Malnutrition and vitamin deficiency are growing concerns in the clinical management of children with autism spectrum disorder (ASD). This case report presents a boy with ASD who developed vitamin A deficiency during follow-up. CASE REPORT: A 7-y-old boy had been diagnosed with ASD and developmental delay at age 18 mo. He developed convulsions associated with hypocalcemia and vitamin D deficiency at 3 y of age. Although vitamin D supplementation was continued, he was only able to eat rice, green tea, and fried potatoes from 3 y of age to age 7 y. He had started rubbing his eyes and had refused to open his eyes 9 mo before. An ophthalmologic examination showed bilateral corneal ulcers and right corneal perforation. Vitamin A was immediately supplemented with a nasogastric tube; however, his right eye was surgically enucleated against the persistent infection. LITERATURE REVIEW: A search of the relevant literature from 1993 to 2020 identified 11 cases of patients with ASD (5-17 y of age) who developed vitamin A deficiency owing to malnutrition. Only 4 cases (36&#37;) had a full recovery in visual acuity. CONCLUSION: Vitamin A deficiency frequently causes irreversible visual impairment in children with ASD. Vigilant monitoring of vitamin levels prevents unfavorable outcomes in children with ASD and difficulty in food intake.

DOI： 10.1016/j.nut.2021.111275

記述言語：英語   掲載種別：研究論文（学術雑誌）   出版者・発行元：Therapeutic Drug Monitoring  

BACKGROUND: Teicoplanin is a glycopeptide antibiotic used for the treatment of methicillin-resistant Staphylococcus aureus infections. To ensure successful target attainment, therapeutic drug monitoring-informed dosage adjustment is recommended. However, it relies on the experience of the clinician and the frequency of drug measurements. This study aimed to design a new optimal dosing regimen of teicoplanin with a maintenance dosing strategy for neonates and children based on their physiological characteristics. METHODS: Data from teicoplanin-treated patients (n = 214) were collected from electronic medical records. Covariate analyses were performed using population pharmacokinetic (PK) modeling with 399 serum teicoplanin concentrations from 48 neonates and 166 children. Multiple PK simulations were conducted to explore optimal dosing regimens that would allow control of the trough concentration to the target of 15-30 mg/L quicker than the current standard regimen. RESULTS: Allometrically scaled body weight, postmenstrual age (PMA), renal function, and serum albumin were implemented as substantial covariates for teicoplanin clearance in a two-compartment PK model. Covariate analyses and comprehensive simulation assessments recommended the following modifications to the current regimen: 1) decreased dose for premature babies (PMA ≤ 28 weeks), 2) decreased dose for children with renal dysfunction, and 3) increased dose for children (0.5-11 years) with an estimated glomerular filtration rate of ≥90 mL/min/1.73 m2. CONCLUSIONS: This study leverages real-world clinical information and proposes new optimal dosing regimens for teicoplanin in neonates and children through PK modeling and simulation analyses, taking into account the age, including PMA, and renal function of patients.

DOI： 10.1097/FTD.0000000000000930

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記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Primary brain tumor is a leading cause of death in cancer-bearing children. Acutely progressive patterns of electroencephalography (EEG) remain to be investigated for children with rapidly growing brain tumors. CASE REPORT: A 14-month-old boy was transferred to our department for prolonged seizures and unrecovered consciousness on his fifth day of illness. The EEG recording on admission showed highly disorganized background activity with high-voltage rhythmic delta waves. Serial EEG monitoring revealed a rapid transition of the background activity to the suppression-burst pattern, and then to generalized suppression of cortical activity within a few hours after admission. Magnetic resonance imaging detected a midline tumor at the pineal gland extending to the midbrain and pons. The tumor was pathologically confirmed as atypical teratoid/rhabdoid tumor (AT/RT) with absent expression of SMARCB1. He died of tumor progression on the 20th day after admission. CONCLUSION: AT/RT is an additional category of brain tumors that cause the clinically and electro-physiologically critical condition in a few days after the onset.

DOI： 10.1016/j.clineuro.2021.106922

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Subacute sclerosing panencephalitis (SSPE) is a slow virus infection associated with mutant measles virus (MeV). The long-term outcome of antiviral treatments remains to be determined. We herein present a Japanese boy who was diagnosed with SSPE at 10 years of age. Intraventricular infusions of interferon-α effectively prevented the progress of symptoms during 14 years of follow-up period. Flow-cytometric analysis demonstrated higher proportion of T helper 17 cells (Th17, 18.2&#37;) than healthy controls (4.8-14.5&#37;) despite the normal subpopulation of peripheral lymphocytes. These data suggest that a group of patients with SSPE may show favorable responses to intraventricular infusions of interferon-α.

DOI： 10.1016/j.jneuroim.2021.577656

記述言語：英語   掲載種別：研究論文（学術雑誌）  

CD71+ erythroid cells (CECs) are recognized to have an immunoregulatory function via direct cell-cell interaction and soluble mediators. Circulating CECs appear in newborns or patients with hemolytic and cardiopulmonary disorders. To assess the biological role of CECs in systemic inflammation, we studied the gene expression and function in systemic-onset juvenile idiopathic arthritis (SoJIA). Peripheral blood mononuclear cells of SoJIA patients expressed upregulated erythropoiesis-related genes. It represented the largest expansion of CECs during active phase SoJIA among other inflammatory diseases. Despite the opposing roles of erythropoietin and hepcidin in erythropoiesis, both serum levels were in concert with the amounts of SoJIA-driven CECs. Circulating CECs counts in inflammatory diseases were positively correlated with the levels of C-reactive protein, IL-6, IL-18, or soluble TNF receptors. Co-culture with active SoJIA-driven CECs suppressed secretions of IL-1β, IL-6, and IL-8 from healthy donor monocytes. The top upregulated gene in SoJIA-driven CECs was ARG2 compared with CECs from cord blood controls, although cytokine production from monocytes was suppressed by co-culture, even with an arginase inhibitor. CECs are driven to the periphery during the acute phase of SoJIA at higher levels than other inflammatory diseases. Circulating CECs may control excessive inflammation via the immunoregulatory pathways, partly involving arginase-2.

DOI： 10.1038/s41598-021-93831-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Predicting outcomes of children after cardiac arrest (CA) remains challenging. To identify useful prognostic markers for pediatric CA, we retrospectively analyzed the early findings of head computed tomography (CT) of patients. Subjects were non-traumatic, out-of-hospital CA patients < 16 years of age who underwent the first head CT within 24 h in our institute from 2006 to 2018 (n = 70, median age: 4 months, range 0-163). Of the 24 patients with return of spontaneous circulation, 14 survived up to 30 days after CA. The degree of brain damage was quantitatively measured with modified methods of the Alberta Stroke Program Early CT Score (mASPECTS) and simplified gray-matter-attenuation-to-white-matter-attenuation ratio (sGWR). The 14 survivors showed higher mASPECTS values than the 56 non-survivors (p = 0.035). All 3 patients with mASPECTS scores ≥ 20 survived, while an sGWR ≥ 1.14 indicated a higher chance of survival than an sGWR < 1.14 (54.5&#37; vs. 13.6&#37;). Follow-up magnetic resonance imaging for survivors validated the correlation of the mASPECTS < 15 with severe brain damage. Thus, low mASPECTS scores were associated with unfavorable neurological outcomes on the Pediatric Cerebral Performance Category scale. A quantitative analysis of early head CT findings might provide clues for predicting survival of pediatric CA.

DOI： 10.1038/s41598-021-91628-y

記述言語：日本語  

記述言語：日本語  

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Importance: The development of Kawasaki disease (KD) has been suggested to be associated with droplet- or contact-transmitted infection; however, its triggers and transmission modes remain to be determined. Under an epidemic of SARS-CoV-2, the COVID-19 state of emergency in Japan served as a nationwide social experiment to investigate the impact of quarantine or isolation on the incidence of KD. Objective: To assess the role of droplet or contact transmission in the etiopathogenesis of KD. Design, Setting, and Participants: This multicenter, longitudinal, cross-sectional study was conducted from 2015 to 2020 at Fukuoka Children's Hospital and 5 adjacent general hospitals. The number of admissions for KD and infectious diseases were analyzed. Participants were pediatric patients admitted to the participating hospitals for KD or infectious diseases. Exposures: Quarantine and isolation owing to the COVID-19 state of emergency. Main Outcomes and Measures: The primary end points were the ratios of patients with KD to patients with respiratory tract or gastrointestinal infections admitted from April to May in 2015 to 2019 and 2020. A Poisson regression model was used to analyze them. Results: The study participants included 1649 patients with KD (median [interquartile range] age, 25 [13-43] months; 901 boys [54.6&#37;]) and 15 586 patients with infectious disease (data on age and sex were not available for these patients). The number of admissions for KD showed no significant change between April and May in 2015 to 2019 vs the same months in 2020 (mean [SD], 24.8 [5.6] vs 18.0 [4.0] admissions per month; 27.4&#37; decrease; adjusted incidence rate ratio [aIRR], 0.73; 95&#37; CI, 0.48-1.10; P = .12). However, the number of admissions for droplet-transmitted or contact-transmitted respiratory tract infections (mean [SD], 157.6 [14.4] vs 39.0 [15.0] admissions per month; 75.3&#37; decrease; aIRR, 0.25; 95&#37; CI, 0.17-0.35; P < .001) and gastrointestinal infections (mean [SD], 43.8 [12.9] vs 6.0 [2.0] admissions per month; 86.3&#37; decrease; aIRR, 0.14; 95&#37; CI, 0.04-0.43; P < .001) showed significant decreases between April and May in 2015 to 2019 vs the same months in 2020 (total, 12 254 infections). Thus, the ratio of KD to droplet- or contact-transmitted respiratory tract and gastrointestinal infections incidence in April and May 2020 was significantly increased (ratio, 0.40 vs 0.12; χ21 = 22.76; P < .001). Conclusions and Relevance: In this study, the significantly increased incidence of KD compared with respiratory tract and gastrointestinal infections during the COVID-19 state of emergency suggests that contact or droplet transmission is not a major route for KD development and that KD may be associated with airborne infections in most cases.

DOI： 10.1001/jamanetworkopen.2021.4475

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Aspergillus is a widespread fungus in the environment, usually invades through the respiratory tract. Invasive aspergillosis is a fatal disseminated infection in immunocompromised hosts. Appendicitis occurs scarcely in patients with leukemia. We report a case of Aspergillus appendicitis that underwent an urgent appendectomy. An 11-year-old boy received the diagnosis of acute myeloid leukemia, because of the bone pain and results of the bone marrow study. He obtained a complete remission after cancer chemotherapy and received peripheral blood stem cell transplantation from a histocompatible sibling. Leukemia relapsed 5 months post-transplant. Induction therapy with etoposide, cytarabine and mitoxantrone was started on Candida prophylaxis. Fifteen days after the end of chemotherapy, he presented with febrile neutropenia and abdominal pain, that did not respond to broad-spectrum antibiotics. Serum levels of C-reactive protein, β-D-glucan and procalcitonin were unremarkable. Computed tomography scan revealed a swollen appendix and the adjacent tissue inflammation. An urgent appendectomy led to a tentative diagnosis of Aspergillus appendicitis based on the histopathological findings of many fungal hyphal forms. Panfungal polymerase chain reaction using DNA extracted from the lesion determined the pathogen of Aspergillus niger. There was no evidence of invasive aspergillosis. During the prolonged anti-fungal therapy, he achieved a remission of leukemia and underwent the second hematopoietic cell transplantation. To our knowledge, Aspergillus appendicitis was reported to occur in 5 leukemia patients. Four of them survived after appendectomy and one died from intestinal perforation. Early surgical intervention is mandatory for a cure of Aspergillus appendicitis in neutropenic patients on Candida prophylaxis.

DOI： 10.1016/j.jiac.2020.07.016

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Human parvovirus B19 (B19V) causes glomerulopathy or microangiopathy, but not tubulopathy. We experienced an 11-year-old girl with spherocytosis who developed acute kidney injury on a primary infection of B19V. She presented with anuria, encephalopathy, thrombocytopenia, and coagulopathy, along with no apparent aplastic crisis. METHODS: Continuous hemodiafiltration, immunoglobulin, and intensive therapies led to a cure. RESULTS: A kidney biopsy resulted in a histopathological diagnosis of tubulointerstitial nephritis without immune deposits. The virus capsid protein was limitedly expressed in the tubular epithelial cells with infiltrating CD8-positive cells. CONCLUSIONS: Viral and histopathological analyses first demonstrated B19-infected tubulointerstitial nephritis due to the aberrant viremia with hereditary spherocytosis.

DOI： 10.1093/ofid/ofaa288

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Hemophagocytic lymphohistiocytosis (HLH) occurs in neonates with disseminated infection of herpes simplex virus (HSV). Little has been reported on the control of rapid HLH progression. We studied the cytokine profile and genetic basis of two index cases with divergent outcomes after early treatment of type 2 HSV infection. One survivor had fever and elevated serum levels of tumor necrosis factor (TNF)-α, interleukin-6 (IL-6), interferon (IFN)-β, and IFN-γ at diagnosis. The other neonate had no fever or TNF-α production, but significant IL-6 or IFN responses during the treatment course, and died 19 days after birth. Among 16 reported cases of neonatal HSV-HLH including index cases, eight deceased neonates experienced significantly less fever at presentation (p = 0.028), lower platelet counts (p = 0.019), and lower ratios of soluble IL-2 receptor (sIL-2R) to ferritin levels (p = 0.044) than eight survivors. The 100-day overall survival rates were significantly higher in patients with fever (p = 0.004), > 100 × 109/L of platelet counts (p = 0.035) or > 20 of sIL-2R/ferritin ratio at diagnosis (p = 0.004). The first febrile and cytokine responses to HSV infection predict the early outcome of neonatal HSV-HLH.

DOI： 10.1007/s12185-019-02738-3

記述言語：英語   掲載種別：研究論文（学術雑誌）  

OBJECTIVES: To characterize the real size and morphology of tracheas in childhood for the optimal selection of endotracheal tube. DESIGN: A retrospective cohort study of pediatric patients who received CT scan of the cervical spine from July 2011 to March 2018. Cross-sectional CT images vertical to trachea were reconstructed and the accurate tracheal diameters were measured. The validity of the traditional age-based formula for predicting the endotracheal tube size was assessed for the best fit to trachea. SETTING: Tertiary Emergency and Critical Care Center of Kyushu University Hospital. PATIENTS: Children, who are 1 month to 15 years old, received CT scan of the cervical spine. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We enrolled 86 children with median age of 53 months. The cross-sectional shape of pediatric trachea was circular at the cricoid level and elliptical at the infraglottic level. The narrowest part of pediatric trachea was the transverse diameter at the infraglottic level at any age. Significant positive correlation between age and the narrowest diameter was observed. When compared the transverse diameter at the infraglottic level with the outer diameter of endotracheal tubes, uncuffed endotracheal tubes selection based on the traditional age-based formula ran a significant risk of oversized endotracheal intubation until 10 years old compared with cuffed endotracheal tubes selection (60.0&#37; vs 23.8&#37;; p < 0.05). CONCLUSIONS: These findings indicate the safety and efficacy of cuffed endotracheal tubes in infants and children and the reconsideration for the airway management in pediatric anesthesia and intensive care.

DOI： 10.1097/PCC.0000000000001996

記述言語：英語   掲載種別：研究論文（学術雑誌）  

BACKGROUND: Bicycle-spoke injuries rarely cause late complications of infection, including sepsis and sepsis-associated encephalopathy, with appropriate treatments. CASE PRESENTATION: We experienced a 2-year-old girl who developed the signs of encephalopathy with fever 6 months after a spoke-injury. On admission, the injured skin was inflamed with cellulitis. The blood culture was positive for methicillin-sensitive Staphylococcus aureus. Electroencephalogram showed diffuse slow-wave activity. Diffusion-weighted magnetic resonance imaging detected a high-intensity lesion with decreased diffusivity at the right frontal cortex. She received immunoglobulin and combined antibiotics treatments in the intensive care unit, and successfully overcame the sepsis-associated encephalopathy without neurological impairments. CONCLUSION: This is the first report demonstrating that sepsis and its associated encephalopathy occurs in a remote period after the bicycle-spoke injury.

DOI： 10.1186/s12879-019-4082-4

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1016/j.jns.2018.10.007

記述言語：英語   掲載種別：研究論文（学術雑誌）  

AIM: It is estimated that 1-5&#37; 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.

DOI： 10.1136/jclinpath-2017-204962

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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&#37; vs. 8&#37;, 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.

DOI： 10.1016/j.eplepsyres.2018.04.006

記述言語：英語   掲載種別：研究論文（学術雑誌）  

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.

DOI： 10.1186/s12941-018-0282-9

記述言語：その他   掲載種別：研究論文（学術雑誌）  

Summary

Calcineurin inhibitors (CNIs) have been used off-label for the treatment of refractory Kawasaki disease (KD). However, it remains unknown whether CNIs show protective effects against the development of coronary artery lesions in KD patients. To investigate the effects of CNIs on coronary arteries and the mechanisms of their actions on coronary arteritis in a mouse model of KD, we performed experiments with FK565, a ligand of nucleotide-binding oligomerization domain-containing protein 1 (NOD1) in wild-type, severe combined immunodeficiency (SCID), caspase-associated recruitment domain 9 (CARD9)–/– and myeloid differentiation primary response gene 88 (MyD88)–/– mice. We also performed in-vitro studies with vascular and monocytic cells and vascular tissues. A histopathological analysis showed that both cyclosporin A and tacrolimus exacerbated the NOD1-mediated coronary arteritis in a dose-dependent manner. Cyclosporin A induced the exacerbation of coronary arteritis in mice only in high doses, while tacrolimus exacerbated it within the therapeutic range in humans. Similar effects were obtained in SCID and CARD9–/– mice but not in MyD88–/– mice. CNIs enhanced the expression of adhesion molecules by endothelial cells and the cytokine secretion by monocytic cells in our KD model. These data indicated that both vascular and monocytic cells were involved in the exacerbation of coronary arteritis. Activation of MyD88-dependent inflammatory signals in both vascular cells and macrophages appears to contribute to their adverse effects. Particular attention should be paid to the development of coronary artery lesions when using CNIs to treat refractory KD.

DOI： 10.1111/cei.13002

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Paroxysmal sympathetic hyperactivity (PSH) is a dysautonomic condition that is associated with various types of acquired brain injuries. Traumatic brain lesions have been documented as the leading cause of PSH. However, detailed clinical features of pediatric PSH caused by intrinsic brain lesions remain to be elusive. We present a 3-year-old boy, who had been diagnosed as having cerebral palsy, developmental delay and epilepsy after perinatal hypoxia-induced brain injury. He developed status epilepticus with fever on the third day of respiratory infection. Whereas the seizure was terminated by systemic infusion of midazolam, consciousness remained disturbed for the next 48h. Serial magnetic resonance imaging studies revealed that acute encephalopathy with biphasic seizures and late reduced diffusion (AESD) evolved on 3days after the seizure. Therapeutic hypothermia was immediately introduced, however, the brain lesion extended to the whole subcortical white matters on day 8. The intermittent bilateral dilation of pupils with increased blood pressure and tachycardia were observed until day 12. Real-time monitoring of electroencephalograms ruled out the recurrent attacks of seizures. The abnormal signs of autonomic nervous system gradually ceased and never relapsed after recovery from the hypothermia. PSH or a transient condition of dysautonomia may emerge and persist during the acute phase of AESD.

DOI： 10.1016/j.braindev.2017.03.023

記述言語：日本語   掲載種別：研究論文（学術雑誌）  

C-Type Lectin Receptor DCAR Recognizes Mycobacterial Phosphatidyl-Inositol Mannosides to Promote a Th1 Response during Infection.
Phosphatidyl-inositol mannosides (PIM) are glycolipids unique to mycobacteria and other related bacteria that stimulate host immune responses and are implicated in mycobacteria pathogenicity. Here, we found that the FcRγ-coupled C-type lectin receptor DCAR (dendritic cell immunoactivating receptor; gene symbol Clec4b1) is a direct receptor for PIM. Mycobacteria activated reporter cells expressing DCAR, and delipidation of mycobacteria abolished this activity. Acylated PIMs purified from mycobacteria were identified as ligands for DCAR. DCAR was predominantly expressed in small peritoneal macrophages and monocyte-derived inflammatory cells in lungs and spleen. These cells produced monocyte chemoattractant protein-1 (MCP-1) upon PIM treatment, and absence of DCAR or FcRγ abrogated MCP-1 production. Upon mycobacterial infection, Clec4b1-deficient mice showed reduced numbers of monocyte-derived inflammatory cells at the infection site, impaired IFNγ production by T cells, and an increased bacterial load. Thus, DCAR is a critical receptor for PIM that functions to promote T cell responses against mycobacteria.

DOI： 10.1016/j.immuni.2016.10.012

記述言語：英語  

Kawasaki disease (KD) is an acute systemic vasculitis of childhood that does not have a known cause or aetiology. The epidemiological features (existence of epidemics, community outbreaks and seasonality), unique age distribution and clinical symptoms and signs of KD suggest that the disease is caused by one or more infectious environmental triggers. However, KD is not transmitted person-to-person and does not occur in clusters within households, schools or nurseries. KD is a self-limited illness that is not associated with the production of autoantibodies or the deposition of immune complexes, and it rarely recurs. Regarding the underlying pathophysiology of KD, innate immune activity (the inflammasome) is believed to play a role in the development of KD vasculitis, based on the results of studies with animal models and the clinical and laboratory findings of KD patients. Animal studies have demonstrated that innate immune pathogen-associated molecular patterns (PAMPs) can cause vasculitis independently of acquired immunity and have provided valuable insights regarding the underlying mechanisms of this phenomenon. To validate this concept, we recently searched for KD-specific PAMPs and identified such molecules with high specificity and sensitivity. These molecules have structures similar to those of microbe-associated molecular patterns (MAMPs), as shown by liquid chromatography-tandem mass spectrometry. We propose herein that KD is an innate immune disorder resulting from the exposure of a genetically predisposed individual to microbe-derived innate immune stimulants and that it is not a typical infectious disease.

DOI： 10.1111/cei.12832

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Objective - Nod1 is an intracellular pattern recognition receptor for bacterial peptidoglycan fragments. We previously reported that a synthetic Nod1 ligand, FK565, induced acute coronary arteritis in mice similar to that of Kawasaki disease. However, the molecular mechanisms underlying this characteristic inflammation have remained elusive. Approach and Results - We found that CD11c MHC class II cells accumulated in the heart of FK565-treated mice before arteritis development. Morphological features and gene expression signatures of the cardiac CD11c MHC class II cells suggested that this population is closely related to macrophages, and thus, we designated them cardiac CD11c macrophages. Nod1 in nonhematopoietic cells, rather than hematopoietic cells, was required for the increase of cardiac CD11c macrophages and arteritis development. Among nonhematopoietic cells, cardiac endothelial cells produced a large amount of chemokines in response to FK565. Endothelial cell-specific blockade of Nod1 signaling suppressed FK565-induced expression of these chemokines, accumulation of cardiac CD11c macrophages, and subsequent coronary arteritis development. We also found that CCR2 Ly6C inflammatory monocytes in peripheral blood supplied precursors of cardiac CD11c macrophages. CCR2-deficient mice or pertussis toxin-treated mice exhibited decreased numbers of cardiac CD11c macrophages and reduced arteritis. Conclusions - These results suggest that Ly6C monocytes are recruited to FK565-activated endothelial cells to generate cardiac CD11c macrophages, which play a pivotal role in the pathogenesis of acute coronary arteritis. + + + + + + + + hi + + hi +

DOI： 10.1161/ATVBAHA.114.304846

記述言語：英語   掲載種別：研究論文（学術雑誌）  

Atherosclerosis is essentially a vascular inflammatory process in the presence of an excess amount of lipid. We have recently reported that oral administration of a nucleotide-binding oligomerization domain (Nod)-1 ligand, FK565, induced vascular inflammation in vivo. No studies, however, have proven the association between Nod1 and atherosclerosis in vivo. To investigate a potential role of NOD1 in atherogenesis, we orally administered FK565 to apolipoprotein E knockout (Apoe(-/-)) mice for 4 wk intermittently and performed quantification of atherosclerotic lesions in aortic roots and aortas, immunohistochemical analyses, and microarray-based gene expression profiling of aortic roots. FK565 administration accelerated the development of atherosclerosis in Apoe(-/-) mice, and the effect was dependent on Nod1 in non-bone marrow origin cells by bone marrow transplantation experiments. Immunohistochemical studies revealed the increases in the accumulation of macrophages and CD3 T cells within the plaques in aortic roots. Gene expression analyses of aortic roots demonstrated a marked upregulation of the Ccl5 gene during early stage of atherogenesis, and the treatment with Ccl5 antagonist significantly inhibited the acceleration of atherosclerosis in FK565-administered Apoe(-/-) mice. Additionally, as compared with Apoe(-/-) mice, Apoe and Nod1 double-knockout mice showed reduced development of atherosclerotic lesions from the early stage as well as their delayed progression and a significant reduction in Ccl5 mRNA levels at 9 wk of age. Data in the present study show that the Nod1 signaling pathway in non-bone marrow-derived cells contributes to the development of atherosclerosis.

DOI： 10.4049/jimmunol.1302841

開催年月日： 2021年10月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：web   国名：日本国  

開催年月日： 2021年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：web   国名：日本国  

開催年月日： 2020年11月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：web   国名：日本国  

開催年月日： 2020年11月

記述言語：日本語  

開催地：web   国名：日本国  

開催年月日： 2020年11月

記述言語：日本語  

開催地：web   国名：日本国  

開催年月日： 2020年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：旭川   国名：日本国  

開催年月日： 2018年11月

記述言語：日本語   会議種別：シンポジウム・ワークショップ パネル（公募）  

開催地：Fukuoka   国名：日本国  

開催年月日： 2018年10月

記述言語：日本語  

国名：日本国  

開催年月日： 2018年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2018年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：Honolulu, Hawaii   国名：アメリカ合衆国  

開催年月日： 2018年7月

記述言語：日本語  

開催地：Sorrent, Italy   国名：イタリア共和国  

開催年月日： 2018年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：大阪   国名：日本国  

開催年月日： 2018年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：横浜   国名：日本国  

開催年月日： 2018年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：東京   国名：日本国  

開催年月日： 2018年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

開催年月日： 2018年7月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

開催年月日： 2018年3月

記述言語：日本語  

開催地：東京   国名：日本国  

開催年月日： 2018年3月

記述言語：日本語   会議種別：口頭発表（一般）  

開催地：福岡   国名：日本国  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

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記述言語：日本語  

4ヵ月女児、咳嗽、多呼吸を主訴とした。咳嗽、鼻汁、喘鳴の増悪にて前医救急外来を受診し、百日咳の疑いで加療されるも呼吸状態の改善は乏しかった。3ヵ月時からコロナウイルス感染症2019の流行拡大があり、医療機関の受診を自粛したため、定期予防接種は全て未接種であった。入院時には呼吸性アシドーシスを呈し、喀痰のPCR検査から百日咳と診断して人工呼吸管理と抗菌薬投与を行い、抜管後、前医へ再転院した。喀痰の細菌培養検査で百日咳菌、肺炎球菌、インフルエンザ菌が検出され、ワクチン接種の遅れにより乳児百日咳に肺炎球菌、インフルエンザ菌の二次感染を合併して肺炎が重症化したと考えられた。

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

川崎病は,主に乳幼児が罹患する中型血管炎を特徴とする全身性の血管炎である。また,冠動脈瘤を形成することによって予後不良となりうる疾患である。症例は心肺停止にて搬送された6ヵ月,男児。病理解剖の結果,全身の広範な血管炎および冠動脈瘤を認め,川崎病血管炎による突然死と診断した。急激な経過をたどった川崎病血管炎の一剖検例を経験したので報告する。(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

＜文献概要＞RSウイルスは主に冬季に流行する乳幼児の下気道感染症の主要な原因ウイルスである.臨床症状や疫学的状況からRSウイルス感染症を疑うが,他の気道感染を起こすウイルスでも類似した症候を示すため,鑑別には病原体診断が必要となる.病原体診断には,ウイルス分離,抗原検査,遺伝子定量検査等がある.遺伝子定量検査のリアルタイムPCR法は現在の検査のなかでは最も感度が高いが,簡便性と迅速性という点ではウイルス抗原検出法を用いた迅速キットのほうに分がある.本稿では,RSウイルス感染症の病原体診断および細菌との共感染やヒトメタニューモウイルス感染症との鑑別について検討し記述する.

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

マクロファージは,生体内で発生した死細胞を速やかに貪食し,恒常性の維持に寄与している.発生の過程や外界からのさまざまなストレスなどにより,つねに死細胞は生成されるが,マクロファージによる死細胞の認識・貪食および,その後の炎症誘導・抑制の反応のメカニズムがつぎつぎに明らかとなってきている.マクロファージが初期アポトーシス細胞を認識・貪食すると抗炎症性サイトカインが産生され,炎症抑制に働く.一方で,ネクローシス細胞から放出されるdamage-associated molecular patterns(DAMPs)を認識すると,炎症性サイトカイン・ケモカインの産生が誘導され,炎症反応が惹起される.死細胞が認識される際の受容体やリガンドにより貪食,炎症誘導または抑制などの反応が異なることが明らかとなってきている.本稿では,死細胞の貪食にかかわる受容体およびDAMPs受容体について概説する.(著者抄録)

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：英語  

記述言語：英語  

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

C型レクチン受容体(CLR)は、カルシウムイオンの存在下に特定の糖鎖を認識して結合する蛋白質で、自然免疫系レセプターファミリーとして注目されている。その一つであるMincleは、主にマクロファージにおいて様々なストレスにより発現が誘導される分子として同定され、ITAM(免疫受容活性化チロシンモチーフ)を介して炎症性シグナルを誘導する。Mincleによるdanger signalおよびpathogenの認識について概説し、アレルギー炎症におけるMincleの役割について述べた。

記述言語：英語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語  

記述言語：日本語