研究者詳細 - 塚原　宏一

論文 - 塚原　宏一

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Local and Systemic Immune Responses to Influenza A Virus Infection in Pneumonia and Encephalitis Mouse Models. 国際誌

Yoshiharu Nagaoka, Nobuyuki Nosaka, Mutsuko Yamada, Masato Yashiro, Yosuke Washio, Kenji Baba, Tsuneo Morishima, Hirokazu Tsukahara

Disease markers 2017 2594231 - 2594231 2017年

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVE: To compare local and systemic profiles between different disease pathologies (pneumonia and encephalitis) induced by influenza A virus (IAV). METHODS: An IAV pneumonia model was created by intranasal inoculation of C57BL/6 mice with influenza A/WSN/33 (H1N1) virus. Lung lavage and blood collection were performed on day 3 after IAV inoculation. Similarly, an IAV encephalitis mouse model was created by direct intracranial IAV inoculation. Cerebrospinal fluid (CSF) and blood collection were conducted according to the same schedule. Cytokine/chemokine profiles were produced for each collected sample. Then the data were compared visually using radar charts. RESULTS: Serum cytokine profiles were similar in pneumonia and encephalitis models, but local responses between the bronchoalveolar lavage fluid (BALF) in the pneumonia model and CSF in the encephalitis model differed. Moreover, to varying degrees, the profiles of local cytokines/chemokines differed from those of serum in both the pneumonia and encephalitis models. CONCLUSION: Investigating local samples such as BALF and CSF is important for evaluating local immune responses, providing insight into pathology at the primary loci of infection. Serum data alone might be insufficient to elucidate local immune responses and might not enable clinicians to devise the most appropriate treatment strategies.

DOI： 10.1155/2017/2594231

Fontan手術後に発症する蛋白漏出性胃腸症の予後に関する検討

栗田佳彦, 馬場健児, 近藤麻衣子, 栄徳隆裕, 塚原宏一, 佐野俊二, 笠原真悟, 岩崎達雄, 佐藤修平, 大月審一

日本小児循環器学会雑誌 33 ( 3 ) 202 - 210 2017年

記述言語：日本語出版者・発行元：特定非営利活動法人日本小児循環器学会

<p>背景：複雑先天性心疾患におけるFontan手術後に発症する蛋白漏出性胃腸症は発症すると難治・治療困難な病態であり生命予後を規定する．本研究の目的は当院でのPLE症例の予後と治療方針の検討である．</p><p>方法：1991～2014年に岡山大学病院でFontan手術後PLEの診断・治療を行った23例を対象にし，転帰の調査と死亡症例の傾向について検討を行った．</p><p>結果：Fontan手術施行401例中の23例（5.7％）に発症．フォローアップ期間は0.8～13年（中央値4.7年）．生存率は5年68％，10年54％．死亡原因は敗血症（2例），PLE増悪による多臓器不全（2例），心不全（1例），頭蓋内出血（1例）．死亡症例はPLE診断年齢が高くFontan手術から診断までの期間が長期であった．血行動態評価では治療前後の心係数（CI）と主心室駆出率（vEF），治療後の中心静脈圧（mCVP）に有意差を認めた．治療後CI＜2.8 L/min/mm, vEF＜50％，mCVP≧15 mmHgの症例は死亡率が高かった．</p><p>結論：PLEに対する治療は一定の有用性を認めたが，予後は満足できるものではない．血行動態的な治療の目標はCI，vEFの改善とCVPを低下させることと思われる．</p>

DOI： 10.9794/jspccs.33.202

Urinary Cross-linked N-terminal Telopeptide of Type I Collagen Levels of Infants with Osteogenesis Imperfecta and Healthy Infants.

Miho Yamashita, Kosei Hasegawa, Yousuke Higuchi, Takayuki Miyai, Ayumi Okada, Hiroyuki Tanaka, Hirokazu Tsukahara

Acta medica Okayama 70 ( 6 ) 435 - 439 2016年12月

記述言語：英語掲載種別：研究論文（学術雑誌）

The urinary cross-linked N-terminal telopeptide of type I collagen (uNTx) levels in infantile osteogenesis imperfecta (OI) have not been well studied. Here we investigated the levels of uNTx in infants with OI and healthy infants. We collected spot urine samples from 30 infants with OI (male/female, 14/16; Sillence classification, I/II/III/IV: 15/3/6/6; age, 5.2±4.4 months) and 120 healthy infants (male/female, 75/45; age, 5.1±4.1 months) for the measurement of uNTx levels. The uNTx levels of the OI infants were significantly lower than those of the healthy infants (mean±SD, 1,363.7±530.1 vs. 2,622.2±1,202.6 nmol BCE/mmol Cr; p＜0.001). The uNTx levels of the infants with type I OI were significantly lower than those of the age-matched healthy infants, although an overlap was observed between the 2 groups. Among the 1-month-old infants, the uNTx levels of the infants with types I, III or IV OI were significantly lower than those of the healthy infants, without overlap (1,622.5±235.8 vs. 3,781.0±1,027.1 nmol BCE/mmol Cr; p＜0.001). These results indicate that uNTx levels are significantly lower in infants with OI than in healthy infants, and they suggest that uNTx might be useful as a reference for diagnosing OI.

【周産期医学必修知識第8版】新生児編未熟児くる病

塚原宏一, 鷲尾洋介, 吉本順子

周産期医学 46 ( 増刊 ) 896 - 899 2016年12月

Development of a Japanese scale for assessment of paediatric normal weight. 国際誌

Nobuyuki Nosaka, Takashi Yorifuji, Emily Knaup, Takashi Muguruma, Ayumi Okada, Hirokazu Tsukahara, Hiroyuki Doi

Resuscitation 105 e11-2 2016年8月

Validity of Mothers' Reports of Children's Weight in Japan.

Nobuyuki Nosaka, Takeo Fujiwara, Emily Knaup, Ayumi Okada, Hirokazu Tsukahara

Acta medica Okayama 70 ( 4 ) 255 - 9 2016年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Estimation methods for pediatric weight have not been evaluated for Japanese children. This study aimed to assess the accuracy of mothers' reports of their children's weight in Japan. We also evaluated potential alternatives to the estimation of weight, including the Broselow tape (BT), Advanced Pediatric Life Support (APLS), and Park's formulae. We prospectively collected cross-sectional data on a convenience sample of 237 children aged less than 10 years who presented to a general pediatric outpatient clinic with their mothers. Each weight estimation method was evaluated using Bland- Altman plots and by calculating the proportion within 10% and 20% of the measured weight. Mothers' reports of weight were the most accurate method, with 94.9% within 10% of the measured weight, the lowest mean difference (0.27kg), and the shortest 95% limit of agreement (－1.4 to 1.9kg). The BT was the most reliable alternative, followed by APLS and Park's formulae. Mothers' reports of their children 's weight are more accurate than other weight estimation methods. When no report of a child's weight by the mother is available, BT is the best alternative. When an aged-based formula is the only option, the APLS formula is preferred.

Breastfeeding and Risk of Kawasaki Disease: A Nationwide Longitudinal Survey in Japan. 国際誌

Takashi Yorifuji, Hirokazu Tsukahara, Hiroyuki Doi

Pediatrics 137 ( 6 ) 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND OBJECTIVES: Kawasaki disease (KD) is the most common cause of childhood-acquired heart disease in developed countries. However, the etiology of KD is not known. Aberrant immune responses are considered to play key roles in disease initiation and breastfeeding can mature immune system in infants. We thus examined the association between breastfeeding and the development of KD. METHODS: We used a nationwide population-based longitudinal survey ongoing since 2010 and restricted participants to a total of 37 630 children who had data on their feeding during infancy. Infant feeding practice was queried at 6 to 7 months of age, and responses to questions about hospital admission for KD during the period from 6 to 30 months of age were used as outcome. We conducted logistic regression analyses controlling for child and maternal factors with formula feeding without colostrum as our reference group. RESULTS: A total of 232 hospital admissions were observed. Children who were breastfed exclusively or partially were less likely to be hospitalized for KD compared with those who were formula fed without colostrum; odds ratios for hospitalization were 0.26 (95% confidence interval: 0.12-0.55) for exclusive breastfeeding and 0.27 (95% confidence interval: 0.13-0.55) for partial breastfeeding. Although the risk reduction was not statistically significant, feeding colostrum only also provided a protective effect. CONCLUSIONS: We observed protective effects of breastfeeding on the development of KD during the period from 6 to 30 months of age in a nationwide, population-based, longitudinal survey in Japan, the country in which KD is most common.

DOI： 10.1542/peds.2015-3919

Adults with germline CBL mutation complicated with juvenile myelomonocytic leukemia at infancy. 国際誌

Michiko Muraoka, Chiho Okuma, Kiichiro Kanamitsu, Hisashi Ishida, Yui Kanazawa, Kana Washio, Masafumi Seki, Motohiro Kato, Junko Takita, Yusuke Sato, Seishi Ogawa, Hirokazu Tsukahara, Megumi Oda, Akira Shimada

Journal of human genetics 61 ( 6 ) 523 - 6 2016年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

Juvenile myelomonocytic leukemia (JMML) appears to be a life-threatening disease and showed poor prognosis even after hematopoietic stem cell transplantation (HSCT) because of high relapse rate. On the other hand, recent molecular analysis revealed the heterogeneity of JMML. Here we report that two JMML patients survived >20 years without HSCT and both patients had uniparental disomy of 11q23 where CBL is located without the phenomenon found in neither Noonan syndrome nor Noonan syndrome-like disorder. We think that some JMML patients with CBL mutation might show the good prognosis in later life after remission of JMML.

DOI： 10.1038/jhg.2016.8

Letter to the Editor regarding the paper by Sun G et al: Elevated serum levels of neutrophil elastase in patients with influenza virus-associated encephalopathy. J Neuro Sci 2015;349:190-195. 国際誌

Nobuyuki Nosaka, Kazuki Hatayama, Yousuke Fujii, Masato Yashiro, Hirokazu Tsukahara, Tsuneo Morishima

Journal of the neurological sciences 364 188 - 188 2016年5月

A novel mutation p.Ser348Cys in FGFR3 causes achondroplasia. 国際誌

Kosei Hasegawa, Rie Fukuhara, Tadashi Moriwake, Hiroyuki Tanaka, Yousuke Higuchi, Miho Yamashita, Hirokazu Tsukahara

American journal of medical genetics. Part A 170A ( 5 ) 1370 - 2 2016年5月

Changes in facial appearance from neonate to adult in 3-M syndrome patient with novel CUL7 gene mutations. 査読国際誌

Kosei Hasegawa, Hiroyuki Tanaka, Yousuke Higuchi, Miho Yamashita, Hirokazu Tsukahara

Journal of pediatric endocrinology & metabolism : JPEM 29 ( 2 ) 241 - 6 2016年2月

記述言語：英語掲載種別：研究論文（学術雑誌）出版者・発行元：WALTER DE GRUYTER GMBH

3-M syndrome (OMIM #273750, #612921, and #614205) is a rare autosomal recessive growth disorder that is characterized by pre- and postnatal growth retardation, normal intelligence, and characteristic faces. This syndrome also has characteristic radiological features, such as slender long bones and tall vertebral bodies. Three genes, cullin 7 (CUL7), coiled-coil domain containing 8, and obscurin-like 1 are genetic candidates of 3-M syndrome. Patients with 3-M syndrome have a characteristic facial appearance, including a triangular face, frontal bossing, an anteverted nose, dolichocephaly, and a long philtrum. However, information on adult 3-M syndrome patients, including facial appearance, is scarce. We report an adult female with 3-M syndrome that was caused by novel compound heterozygous mutations (c.4023-1 G>A in splice acceptor site of exon 22 and c.4359_4363dupGGCTG in exon 23) in the CUL7 gene. We also report the growth chart and changes in facial appearance of this patient from the neonate to adult.

DOI： 10.1515/jpem-2015-0272

HDR syndrome in a Japanese girl with biliary atresia: a case report. 国際誌

Yousuke Higuchi, Kosei Hasegawa, Miho Yamashita, Yousuke Fujii, Hiroyuki Tanaka, Hirokazu Tsukahara

BMC pediatrics 16 14 - 14 2016年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Hypoparathyroidism, sensorineural deafness, and renal dysplasia (HDR) syndrome is an autosomal dominant disorder. We report the first detailed case of hypoparathyroidism complicated by biliary atresia. CASE PRESENTATION: A 1-year-old Japanese girl was admitted to our hospital for living donor liver transplantation. She suffered from obstructive jaundice owing to biliary atresia. She also had persistent hypocalcemia. Despite oral calcium and abundant vitamin D supplementation, a laboratory test showed hypocalcemia (1.4 mmol/l) and hyperphosphatemia (2.6 mmol/l). The intact parathyroid hormone level was normal (66 ng/l) with severe vitamin D deficiency (25-hydroxy vitamin D: undetectable levels). There were no rachitic changes in metaphysis on X-rays. Her family history showed that her mother had sensorineural deafness, a low serum calcium level (2.1 mmol/l), hypoplastic left kidney, and a past history of an operation for right vesicoureteral reflux. We suspected that this patient and her mother have hypoparathyroidism, sensorineural deafness, and renal dysplasia syndrome. A heterozygous GATA3 gene mutation (c.736delGinsAT) was found in this patient and her mother, but not in her father. CONCLUSION: This familial case confirms the importance of family history in the diagnosis of HDR syndrome. Regardless of marked vitamin D deficiency, the complication of hypoparathyroidism prevented the onset of vitamin D deficiency rickets in our patient.

DOI： 10.1186/s12887-016-0550-9

Evaluation of rapid immunochromatographic tests for norovirus in neonatal and infant faecal specimens. 国際誌

Nobumasa Takahashi, Ikuko Nojima, Tooru Araki, Mizue Takasugi, Tomoko Sakane, Aya Kodera, Masanori Ikeda, Hirokazu Tsukahara

The Journal of international medical research 43 ( 5 ) 648 - 52 2015年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

OBJECTIVES: To compare the diagnostic performance of two norovirus rapid immunochromatographic kits (QuickNavi(®)-Norovirus [QN] and QuickNavi®-Norovirus 2 [QN2]; Denka Seiken, Niigata, Japan) for neonatal and infant faecal specimens. METHODS: Monthly faecal samples were collected from infants from birth to 12 months of age, and tested for norovirus using QN and QN2. Real-time reverse transcription polymerase chain reaction (RT-PCR) was used as the gold standard for norovirus detection. The diagnostic performance of the kits was calculated. RESULTS: A total of 343 specimens from 81 infants were analysed. In all samples, the specificity of QN and QN2 was 80% (275/343) and 99% (339/343), respectively. In infants aged <1 month, the specificity of QN was 33% (23/70), increasing to 93% at 4 months of age. Specificity of QN2 was ≥94% in infants between 0 and 12 months of age. CONCLUSIONS: QN2 offers improved performance and is more useful than QN for the diagnosis of norovirus infection in the neonatal and infant period.

DOI： 10.1177/0300060515592902

Anti-high mobility group box-1 monoclonal antibody treatment provides protection against influenza A virus (H1N1)-induced pneumonia in mice. 国際誌

Nobuyuki Nosaka, Masato Yashiro, Mutsuko Yamada, Yosuke Fujii, Hirokazu Tsukahara, Keyue Liu, Masahiro Nishibori, Akihiro Matsukawa, Tsuneo Morishima

Critical care (London, England) 19 ( 1 ) 249 - 249 2015年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

INTRODUCTION: Provision for the emergence of an influenza pandemic is an urgent issue. The discovery of a novel anti-influenza therapeutic approach would increase the effectiveness of traditional virus-based strategies. This study was undertaken to evaluate the therapeutic effects of anti-high mobility group box-1 (HMGB1) monoclonal antibody (mAb) treatment on influenza A virus (H1N1)-induced pneumonia in mice. METHODS: Nine-week-old male C57BL/6 mice were inoculated with H1N1, then anti-HMGB1 mAb or control mAb were administered intravenously at 1, 24 and 48 hours after H1N1 inoculation and the survival rate was analyzed. Lung lavage and histopathological analysis were performed on days 3, 5, 7 and 10 after inoculation. RESULTS: Anti-HMGB1 mAb significantly improved the survival rate of H1N1-inoculated mice (1 out of 15 versus 8 out of 15 deaths in the anti-HMGB1 mAb-treated group versus the control mAb-treated group, p < 0.01), although the treatment did not affect virus propagation in the lungs. The treatment also significantly attenuated histological changes and neutrophil infiltration in the lungs of H1N1-inoculated mice. This was associated with inhibition of HMGB1 and suppression of inflammatory cytokine/chemokine expression and oxidative stress enhancement, which were observed in H1N1-inoculated mice. The expression of receptor for advanced glycation end products and nuclear factor κB was attenuated by the treatment. CONCLUSIONS: Anti-HMGB1 mAb may provide a novel and effective pharmacological strategy for severe influenza virus infection in humans by reducing the inflammatory responses induced by HMGB1.

DOI： 10.1186/s13054-015-0983-9

Inhibitory Effects of Edaravone, a Free Radical Scavenger, on Cytokine-induced Hyperpermeability of Human Pulmonary Microvascular Endothelial Cells:A Comparison with Dexamethasone and Nitric Oxide Synthase Inhibitor.

Yukie Saito, Yousuke Fujii, Masato Yashiro, Mitsuru Tsuge, Nobuyuki Nosaka, Nobuko Yamashita, Mutsuko Yamada, Hirokazu Tsukahara, Tsuneo Morishima

Acta medica Okayama 69 ( 5 ) 279 - 90 2015年

記述言語：英語掲載種別：研究論文（学術雑誌）

Lung hyperpermeability affects the development of acute respiratory distress syndrome (ARDS), but therapeutic strategies for the control of microvascular permeability have not been established. We examined the effects of edaravone, dexamethasone, and N-monomethyl-L-arginine (L-NMMA) on permeability changes in human pulmonary microvascular endothelial cells (PMVEC) under a hypercytokinemic state. Human PMVEC were seeded in a Boyden chamber. After monolayer confluence was achieved, the culture media were replaced respectively by culture media containing edaravone, dexamethasone, and L-NMMA. After 24-h incubation, the monolayer was stimulated with tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β). Fluorescein-labeled dextran was added. Then the trans-human PMVEC leak was measured. Expressions of vascular endothelial-cadherin (VE-cadherin) and zonula occludens-1 protein (ZO-1) were evaluated using real-time quantitative polymerase chain reaction and immunofluorescence microscopy. The results showed that TNF-α＋IL-1β markedly increased pulmonary microvascular permeability. Pretreatment with edaravone, dexamethasone, or L-NMMA attenuated the hyperpermeability and inhibited the cytokine-induced reduction of VE-cadherin expression on immunofluorescence staining. Edaravone and dexamethasone increased the expression of ZO-1 at both the mRNA and protein levels. Edaravone and dexamethasone inhibited the permeability changes of human PMVEC, at least partly through an enhancement of VE-cadherin. Collectively, these results suggest a potential therapeutic approach for intervention in patients with ARDS.

Changes of lipoproteins in phenylalanine hydroxylase-deficient children during the first year of life. 査読国際誌

Hironori Nagasaka, Hirokazu Tsukahara, Yoshiyuki Okano, Ken-ichi Hirano, Toshihiro Sakurai, Shu-Ping Hui, Toshihiro Ohura, Hiromi Usui, Tohru Yorifuji, Satoshi Hirayama, Akira Ohtake, Takashi Miida

Clinica chimica acta; international journal of clinical chemistry 433 1 - 4 2014年6月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Influence of hyperphenylalaninemia on lipoproteins in early life remains unclear. METHODS: We enrolled 24 phenylalanine hydroxylase (PAH)-deficient children who were classified into a phenylketonuria (PKU) group (n=12) lacking PAH activity and a benign hyperphenylalaninemia (HPA) group (n=12) having partial PAH activity, and their 11 non-affected siblings. We measured serum total-cholesterol, low-density lipoprotein (LDL)-cholesterol, and high-density lipoprotein (HDL)-cholesterol levels together with apolipoproteins for the first year of life, and compared them with those of 30 age-matched healthy controls. RESULTS: The affected groups invariably had lower cholesterol levels than non-affected groups. At birth, HDL-cholesterol decrease was greatest and predominated over the LDL-cholesterol decrease: total cholesterol, 28/36% decrease to the control level in HPA/PKU; HDL-cholesterol, 33/51%; LDL-cholesterol, 20/28%. At 3months, the opposite changes were observed: total cholesterol, 16/28%; HDL-cholesterol, 13/23%; LDL-cholesterol, 16/33%. At 12months, LDL were still significantly lower in both groups (8/18%, p<.05 and .001), although HDL was significantly decreased only in the PKU group (15%, p<.05). Apolipoprotein A-I/A-II and B changed respectively in accordance with HDL-cholesterol and LDL-cholesterol changes. Despite similar phenylalanine levels, the PKU group invariably had lower cholesterol concentrations than the HPA group had. CONCLUSION: Irrespective of phenylalanine concentrations, lipoprotein synthesis in PAH-deficient children, particularly in PKU children, was suppressed in early life.

DOI： 10.1016/j.cca.2014.02.020

Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. 国際誌

Mitsuru Tsuge, Takashi Oka, Nobuko Yamashita, Yukie Saito, Yosuke Fujii, Yoshiharu Nagaoka, Masato Yashiro, Hirokazu Tsukahara, Tsuneo Morishima

Journal of neurovirology 20 ( 1 ) 73 - 84 2014年2月

記述言語：英語掲載種別：研究論文（学術雑誌）

Viral infections have been implicated as a cause of complex seizures in children. The pathogenic differences in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis remain unclear. This study analyzed the gene expression profiles in the peripheral whole blood from pediatric patients with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. The gene expression profiles of ten patients (five with seizures and five without) with influenza A(H1N1)pdm09 and six patients (three with seizures and three without) with rotavirus gastroenteritis were examined. Gene expression profiles in the whole blood were different in complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis. Transcripts related to the immune response were significantly differentially expressed in complex seizures with influenza A(H1N1)pdm09, and transcripts related to the stress response were significantly differentially expressed in complex seizures with rotavirus gastroenteritis. Pathway analysis showed that the mitogen-activated protein kinases in the T cell receptor signaling pathway were activated in complex seizures due to influenza A(H1N1)pdm09. Dysregulation of the genes related to immune response or stress response could contribute to the pathogenic differences of the complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.

DOI： 10.1007/s13365-013-0231-5

気管支肺異形成症の早期予測におけるカルボキシヘモグロビンの有用性

徳力周子, 奥野貴士, 巨田元礼, 大嶋勇成, 塚原宏一

日本未熟児新生児学会雑誌 25 ( 3 ) 470 - 470 2013年11月

Pathogenic mechanisms of influenza A(H1N1)pdm09 infection elucidated on gene expression profiling. 国際誌

Nobuko Yamashita, Hirokazu Tsukahara, Mitsuru Tsuge, Yoshiharu Nagaoka, Masato Yashiro, Yukie Saito, Yosuke Fujii, Takashi Oka, Tsuneo Morishima

Pediatrics international : official journal of the Japan Pediatric Society 55 ( 5 ) 572 - 7 2013年10月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The pathogenic mechanisms underlying influenza A(H1N1)pdm09-associated central nervous system (CNS) manifestations and pneumonia remain unclear. This study examined A(H1N1)pdm09 host responses using gene expression profiles of patients' peripheral blood. METHODS: Sixteen A(H1N1)pdm09-infected children in three groups were examined: a CNS group, with convulsion and altered consciousness (n = 6); a pneumonia (Pneu) group (n = 5); and a group of infected control patients (n = 5). The signal ratios of the acute to recovery phases in CNS or Pneu were analyzed versus those of the control. RESULTS: The CNS (619 transcripts) and Pneu (656 transcripts) groups had significantly increased signal ratios compared to the control group. Regarding the increased ratios of transcripts shown by multiple probes, contactin-associated protein-like 3 transcripts, oleoyl-ACP hydrolase transcripts, and interleukin 1 type 1 receptor were observed in CNS and Pneu. Increased ratios of prostaglandin-endoperoxide synthase 2 and α-synuclein were characteristic of CNS. Alkaline phosphatase and the Fc fragment of IgA receptor were characteristic of Pneu. Regarding enriched gene ontology terms, 'response to lipopolysaccharide', 'innate immune response', and 'intrinsic to membrane' were observed commonly in CNS and Pneu. Enriched gene ontology terms related to 'hemoglobin' and 'hemostasis' were, respectively, characteristic of CNS and Pneu. CONCLUSION: These symptom-associated transcripts might be some clues to the pathogenesis of the A(H1N1)pdm09 infection.

DOI： 10.1111/ped.12139

Prognostic value of brain injury biomarkers in acute encephalitis/encephalopathy. 国際誌

Hirokazu Tsukahara, Yosuke Fujii, Kousaku Matsubara, Mutsuko Yamada, Yoshiharu Nagaoka, Yukie Saito, Masato Yashiro, Mitsuru Tsuge, Shinichiro Goto, Tetsuro Kitamura, Atsuko Hata, Takashi Ichiyama, Tsuneo Morishima

Pediatrics international : official journal of the Japan Pediatric Society 55 ( 4 ) 461 - 4 2013年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Acute encephalitis/encephalopathy (AEE) is a devastating cause of severe neurodevelopmental sequelae or death in children. Assessing ongoing brain injury and predicting outcomes using bedside point-of-care testing is expected to be extremely valuable. METHODS: For this study, three brain injury markers, S-100B, glial fibrillary acidic protein (GFAP), and tau protein, were measured in early cerebrospinal fluid samples of children with AEE. Subjects comprised three groups: Group 1 (non-AEE control, n = 27); Group 2 (AEE with normal resolution or mild sequelae, n = 13); and Group 3 (AEE with severe sequelae or death, i.e. "poor outcome," n = 10). RESULTS: All marker levels were significantly higher in Group 3 than in Group 1 or 2. In Group 3, only S-100B was significantly higher in non-survivors than in survivors. For scoring assessment (range: 0-3 points), the predictive accuracies of 3 points for poor outcomes in children with AEE (i.e. Group 2 and 3, n = 23) were 91% (21/23) for S-100B, 74% (17/23) for GFAP, and 78% (18/23) for tau. When the scores were summed up for S-100B, GFAP, and tau (range: 0-9 points), and for S-100B and tau (range: 0-6 points), the patients with poor outcomes were identified more accurately using the respective thresholds of 6 points and 4 points (96% [22/23] and 100% [23/23], respectively). CONCLUSION: Our findings suggest that combined measurement and scoring assessment of the markers, especially S-100B and tau, show promise as predictors of clinical outcomes in children with AEE.

DOI： 10.1111/ped.12094

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