論文 - 津川　毅

Longitudinal analysis of VP7 gene of group A human rotavirus G2P[4] strains circulating in the pre-vaccine era in Sapporo, Japan from 1991 to 2011.

Masatoshi Tatsumi, Yoshinobu Nagaoka, Takeshi Tsugawa, Yuko Yoto, Tsukasa Hori, Hiroyuki Tsutsumi

Microbiology and immunology ( WILEY-BLACKWELL )  58 ( 9 ) 540 - 4  2014年09月  [査読有り]  [国際誌]

　概要を見る

Sequence analysis of the VP7 gene in 23 group A human rotavirus G2P[4] strains obtained during 1991-2011, that is, the pre-vaccine era, in Sapporo, Japan showed considerable genetic diversity, mainly in variable regions. Recent G2P[4] epidemic strains were located in sublineage IVa with a distinctive substitution of D96N. This study provides background data on the genetic variability of G2P[4] rotavirus-VP7 gene prior to the widespread use of rotavirus vaccines in Japan.

DOI PubMed

Rhabdomyolysis associated with human parvovirus B19 infection in a patient with Fukuyama-type congenital muscular dystrophy.

Aki Ishikawa, Yuko Yoto, Kazuhiro Ohya, Takeshi Tsugawa, Hiroyuki Tsutsumi

Journal of child neurology ( SAGE PUBLICATIONS INC )  29 ( 7 ) 977 - 9  2014年07月  [査読有り]  [国際誌]

　概要を見る

Patients with Fukuyama-type congenital muscular dystrophy sometimes experience transient exacerbations of muscle weakness. We took care of a 9-year-old boy with Fukuyama-type congenital muscular dystrophy who presented with acute respiratory failure and decreased exercise ability with marked elevation of serum creatine kinase indicating rhabdomyolysis. At that time, his younger sister suffered from erythema infectiosum. Although he had no particular symptoms, he was tested and proven to have acute human parvovirus B19 infection based on detection of anti-B19 IgM and parvovirus B19 DNA in his serum. His acute rhabdomyolysis was possibly triggered by human parvovirus B19 infection.

DOI PubMed

trisomy8が診断の一助となった小児期発症腸管Behcet病の1例

木澤 敏毅, 津川 毅, 竹内 孝子, 鎌崎 穂高, 要藤 裕孝, 五十嵐 敬太, 山本 雅樹, 堀 司, 畠山 直樹, 斉藤 淳人, 東海林 黎吉, 堤 裕幸

小児リウマチ ( (一社)日本小児リウマチ学会 )  5 ( 1 ) 52 - 56  2014年06月  [査読有り]

　概要を見る

腸管Behcet病と診断した12歳男児を経験した。児は幼少時より非周期的に反復する発熱、口腔内アフタを呈し、血液検査では炎症反応の上昇を認めていたが各種培養は陰性であった。不明熱、周期性発熱としてCT、MRI、シンチグラムに加え、骨髄穿刺を施行したところ、染色体検査でtrisomy 8と判明した。trisomy 8の存在から腸管Behcet病を疑い内視鏡検査を実施したところ、食道下部及び回盲部に円形の潰瘍を複数個所に認めたため、trisomy 8に伴う腸管Behcet病と診断した。trisomy 8に伴う骨髄異形成症候群(myelodysplastic syndrome:MDS)の報告が散見されているが、血球系には異常を認めなかった。不明熱の診断過程にて骨髄染色体の異常が診断につながった希有な症例であり、腸管Behcet病の発症機序を考えるうえで非常に興味深い症例と考えられた。(著者抄録)

Virulence-associated genome mutations of murine rotavirus identified by alternating serial passages in mice and cell cultures.

Takeshi Tsugawa, Masatoshi Tatsumi, Hiroyuki Tsutsumi

Journal of virology ( AMER SOC MICROBIOLOGY )  88 ( 10 ) 5543 - 58  2014年05月  [査読有り]  [国際誌]

担当区分：   筆頭著者  , 責任著者

　概要を見る

UNLABELLED: Although significant clinical efficacy and safety of rotavirus vaccines were recently revealed in many countries, the mechanism of their attenuation is not well understood. We passaged serially a cell culture-adapted murine rotavirus EB strain in mouse pups or in cell cultures alternately and repeatedly and fully sequenced all 11 genes of 21 virus samples passaged in mice or in cell cultures. Sequence analysis revealed that mouse-passaged viruses that regained virulence almost consistently acquired four kinds of amino acid (aa) substitutions in VP4 and substitution in aa 37 (Val to Ala) in NSP4. In addition, they gained and invariably conserved the 3' consensus sequence in NSP1. The molecular changes occurred along with the acquisition of virulence during passages in mice and then disappeared following passages in cell cultures. Intraperitoneal injection of recombinant NSP4 proteins confirmed the aa 37 site as important for its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence. IMPORTANCE: Serial passage of a virulent wild-type virus in vitro often results in loss of virulence of the virus in an original animal host, while serial passage of a cell culture-adapted avirulent virus in vivo often gains virulence in an animal host. Actually, live attenuated virus vaccines were originally produced by serial passage in cell cultures. Although clinical efficacy and safety of rotavirus vaccines were recently revealed, the mechanism of their attenuation is not well understood. We passaged serially a murine rotavirus by alternating switch of host (mice or cell cultures) repeatedly and sequenced the eleven genes of the passaged viruses to identify mutations associated with the emergence or disappearance of virulence. Sequence analysis revealed that changes in three genes (VP4, NSP1, and NSP4) were associated with virulence in mice. Intraperitoneal injection of recombinant NSP4 proteins confirmed its diarrheagenic activity in mice. These genome changes are likely to be correlated with rotavirus virulence.

DOI PubMed

【小児内分泌学の進歩2015】カルシウム代謝 副甲状腺腫の確定までに長期間を要した原発性副甲状腺機能亢進症の1例

竹内 孝子, 鎌崎 穂高, 津川 毅, 要藤 裕孝, 近藤 敦, 山 直也, 荻野 次郎, 堤 裕幸

ホルモンと臨床 ( (有)医学の世界社 )  62 ( 5 ) 431 - 434  2014年05月  [査読有り]

Characterization of the NSP4 gene of group A human rotavirus G1P[8] strains circulating in Sapporo, Japan from 1987 to 2000.

Masatoshi Tatsumi, Yoshinobu Nagaoka, Takeshi Tsugawa, Yuko Yoto, Tsukasa Hori, Hiroyuki Tsutsumi

Journal of medical virology ( WILEY-BLACKWELL )  86 ( 2 ) 354 - 9  2014年02月  [査読有り]  [国際誌]

　概要を見る

The genetic diversity of the NSP4 gene of rotavirus G1P[8] strains obtained in Sapporo was analyzed, Japan from 1987 to 2000. Sixty-four strains, which were distributed across the whole study period, were included. All G1P[8] NSP4 genes detected in this study belonged to genotype E1, which divided into at least three lineages. The Sapporo rotavirus G1P[8] isolates were found in each lineage. The mean estimated substitution rate was 1.40 × 10(-3) nucleotide substitutions per site per year, which was comparable to that of the G1P[8] VP7 gene. Comparison of the deduced NSP4 amino acid sequences showed genetic diversity at the center of antigenic site II, but not in the enterotoxic domain. This report represents the first investigation of the genetic diversity and evolution of group A rotavirus NSP4 genes in Asia.

DOI PubMed

Phylogenetic and computational structural analysis of VP7 gene of group a human rotavirus G1P[8] strains obtained in Sapporo, Japan from 1987 to 2000.

Yoshinobu Nagaoka, Masatoshi Tatsumi, Takeshi Tsugawa, Yuko Yoto, Hiroyuki Tsutsumi

Journal of medical virology ( WILEY-BLACKWELL )  84 ( 5 ) 832 - 8  2012年05月  [査読有り]  [国際誌]

　概要を見る

Many studies indicate that G1P[8] genotypes are the most prevalent rotavirus strains worldwide. Although two vaccines have been licensed and their value proven in many countries, continuous surveillance for genetic evolution of circulating rotavirus strains before and after the introduction of the vaccines is desirable. G and P typing were carried out on all field strains isolated during 1987-2000 in Sapporo, Japan. Phylogenetic analysis for the VP7 gene of rotavirus G1P[8] strains was performed. Amino acid substitutions were mapped on the predicted three-dimensional VP7 protein image. G1P[8] genotype predominated. One hundred thirteen strains with G1P[8] genotype were analyzed. Phylogenetic studies of the VP7 gene classified these strains into three lineages. The mean estimated substitution rate was 7.25 × 10(-4) nucleotide substitutions per site per year. One predominant lineage contained the mutant strains which had VP7 amino acid substitutions at residue 91 and 212 that is in the neutralization domains. They were estimated to locate in or near intersubunit boundary of VP7 trimer. It is suggested that the most prevalent G1P[8] lineage strains in Sapporo obtained some survival advantages by changing the neutralization domains of VP7.

DOI PubMed

Detection of enteric viruses in rectal swabs from children with acute gastroenteritis attending the pediatric outpatient clinics in Sapporo, Japan.

Kaori Nakanishi, Takeshi Tsugawa, Shinjiro Honma, Shuji Nakata, Masatoshi Tatsumi, Yuko Yoto, Hiroyuki Tsutsumi

Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology ( ELSEVIER SCIENCE BV )  46 ( 1 ) 94 - 7  2009年09月  [査読有り]  [国際誌]

　概要を見る

BACKGROUND: Gastroenteritis is a world-wide disorder. Numerous studies to identify causative viral agents have been reported for hospitalized patients but there are only a few for outpatients with mild symptoms who are usually managed in the outpatient clinics. OBJECTIVES: Our aim was to clarify the epidemiological and clinical characteristics of acute gastroenteritis in children who visited the outpatient clinics with various complaints suggestive of gastroenteritis. STUDY DESIGN: From December 2003 to December 2005, 877 rectal swabs were collected from patients attending outpatient clinics in Sapporo, Japan. Viral genomes of major five enteric viruses (rotavirus, norovirus, adenovirus, astrovirus and sapovirus) and bocavirus were investigated by RT-PCR or PCR. RESULTS: At least one viral agent was found in 326 (37.2%) cases of the 877 studied. Rotaviruses were the most prevalent and were detected in 143 (16.3%) followed by norovirus in 116 (13.2%), adenovirus in 42 (4.8%), astrovirus in 40 (4.6%) and sapovirus in 15 (1.7%) cases. Bocavirus was detected in only 4 (0.5%) cases. Frequent diarrhea and frequent vomiting were prominent in rotavirus and norovirus infection, respectively. CONCLUSIONS: The prevalence of each enteric virus in outpatients resembled that previously estimated in hospitalized patients, although the detection rate of rotavirus was slightly low. The contribution of bocavirus appears to be small.

DOI PubMed

Guillain-Barre syndrome with meningoencephalitis after Campylobacter jejuni infection.

Takeshi Tsugawa, Koki Nikaido, Toshiaki Doi, Michiaki Koga, Keiichiro Susuki, Tomoki Kubota, Hiroyuki Tsutsumi

The Pediatric infectious disease journal ( LIPPINCOTT WILLIAMS & WILKINS )  23 ( 10 ) 966 - 8  2004年10月  [査読有り]  [国際誌]

担当区分：   筆頭著者

　概要を見る

A 14-year-old boy presented with progressive ascending muscle weakness, urinary retention and disturbed consciousness. Initially his cerebrospinal fluid showed pleocytosis, and protein-cellular dissociation developed later. Campylobacter jejuni was isolated from his stool and serum anti-ganglioside antibodies were positive. Our case suggests that coexistence of meningoencephalitis at an early stage of illness does not necessarily exclude the diagnosis of Guillain-Barre syndrome.

DOI PubMed

急速に脳ヘルニアに陥り,死亡した劇症型急性散在性脳脊髄炎の1例

二階堂 弘輝, 津川 毅, 土井 俊明, 堤 裕幸, 菊地 成佳, 関 公平, 平木 雅久

小児科臨床 ( (株)総合医学社 )  57 ( 6 ) 1194 - 1198  2004年06月  [査読有り]

　概要を見る

4歳4ヵ月男児.発熱を主訴に近医を受診,急性気道炎の診断で加療されたが,発症から3日目に頭痛が出現して再診時に1分間の顔色不良・意識減損,項部硬直を認めたため髄膜炎を疑われ紹介入院となった.入院時,髄液蛋白の異常高値を認め,頭部MRIのT2強調像で両側小脳皮質と大脳白質部に多発性の高信号域を認めたことから,急性散在性脳脊髄炎と診断してメチルプレドニゾロンのパルス療法を開始した.しかし,薬剤抵抗性のけいれん重積状態が続き,脳ヘルニアと考えられる呼吸不全に陥り,免疫グロブリン大量療法や脳低温療法を施行したが効果なく,発症1週間後に死亡した.剖検は得られなかったが,MRI所見やCT像の経時的変化から一番症状の激しかった小脳病変または大脳白質部病変の増悪,あるいはその両方によって生じた脳ヘルニアが脳血流低下を引き起こして大脳組織の壊死が起こったものと推測された

Intracranial hypertension in a boy with Mycoplasma pneumoniae infection: the first report.

Sari Masutani, Rumiko Takayama, Takeshi Tsugawa, Koki Nikaido, Toshiaki Doi, Hiroyuki Tsutsumi

Scandinavian journal of infectious diseases ( TAYLOR & FRANCIS AS )  36 ( 9 ) 700 - 1  2004年  [査読有り]  [国際誌]

　概要を見る

We describe a 7-y-old boy who developed idiopathic intracranial hypertension (IIH) during the convalescent phase of Mycoplasma pneumoniae (M. pneumoniae) infection. Anti-M. pneumoniae antibody and cold hemagglutinin titer were extremely high during his course, and corticosteroid administration was noticeably effective. It supports an immunopathological mechanism for his intracranial hypertension.

DOI PubMed