1993 年度実績報告書

単一遺伝子病の分子・細胞生物学的研究、疾患発症の分子機構の解明

研究課題

研究課題/領域番号	04260102
研究機関	熊本大学
研究代表者	松田一郎熊本大学, 医学部, 教授 (10000986)
研究分担者	衛藤義勝東京慈恵会医科大学, 医学部, 助教授 (50056909) 岡田伸太郎大阪大学, 医学部, 教授 (30028609) 折居忠夫岐阜大学, 医学部, 教授 (20045339) 北川照男日本大学, 医学部, 教授 (50058765) 成澤邦明東北大学, 医学部, 教授 (90004647)
キーワード	先天代謝異常 / 遺伝子解析 / モデル動物 / レセプター異常 / 細胞小器官異常 / 遺伝子導入 / 遺伝子発現
研究概要	1.新しい遺伝子の単離・同定とその変異解析ホロカルボキシラーゼ合成酵素(成沢)、ガラクトセレブロシダーゼ、クラベ病病因酵素(岡田)、フマリルアセト酢酸分解酵素、高チロジン血症I型病因酵素(松田)、betaヒドロキシフェニルピルビン酸酸化酵素、高チロジン血症III型病因酵素(松田)などの遺伝子が世界に先駆けて単離・同定された。ホモカルボキシラーゼ合成酵素欠損症、高チロジン血症I型については変異遺伝子が同定された。また高チロジン血症III型についてはモデル動物でexon 7のスキップが見出された。ムコ多糖体症(折居)のII,IVA,VIIの各型についての責任遺伝子の単離・同定、さらに変異遺伝子の解析が行われた。いずれも世界最初である、IVA型の変異遺伝子の中には日本人、欧米人に共通してdouble gene deletionがあることを見い出した。 2.新しい酵素異常症の責任遺伝子の単離・同定極長鎖アシルCoAデヒドロゲナーゼ欠損症を、11例の患者で確認し、さらにその責任遺伝子、変異遺伝子を単離・同定した(橋本)。 3.遺伝子治療を目標とした基礎研究 Gaucher病、metachromatic leukodystrophyの変異遺伝子解析を日本人患者について行い、それぞれ60%,50%に特定の変異遺伝子が見出された。さらに、マウス骨髄細胞を目標細胞に選びそれぞれの遺伝子(cDNA)をレトロウイルスベクターを用いて遺伝子導入を試み、成功した。 4.糖尿病の遺伝子解析ミトコンドリア遺伝子tRNA^<LEU(UUR)>の3243A→Gの変異について、母子共にIDDMの300家系をスクリーニングし、4家系にそれをみつけた。またslowly progressive IDDMの患者27名中3名にも同じ変異遺伝子をみつけた(岡)。NIDDMの患者について、グリコーゲン合成酵素遺伝子多型を解析し、一部の患者で特定の遺伝子多型との間に有意の相関を見出した(北川)。 5.トランスジェニックマウスを用いた研究疾患モデル動物の作製に際して、遺伝子の相関組み換え率を高めるため、ベクターの安定性について検討した(島田)、その結果、3′末端部位を修飾することで、その目的を達することができることが判明した。 6.哺乳類発生異常の遺伝解析マウスMHCのK領域の近くに胎生致死をおこすt^<w5>変異が存在することも見出し、その変異遺伝子の単離同定を試みた(阿部)。また同定に成功していないが、有力な候補者を見出し研究を続けている。

研究成果
(62件)

すべてその他

すべて文献書誌 (62件)

[文献書誌] Horie K,et al.: "Structure of replacement vectors for efficient gene targeting." J.Biochem.(Tokyo). (in press).
[文献書誌] Nomura M.,et al.: "Isolation and characterization of retinoic acid inducible cDNA clones in F9 cells:One of the early inducible clones encodes oa novel protein sharing several highly homologus regions with a Drosophila polyhomcotic protein" Differentiation. (in press).
[文献書誌] Horie K.,et al.: "Gene targeting by vector with hairpin-shaped oligonucleotide caps." Biochem.Mol.Bio.Internatl.(in press).
[文献書誌] Katagiri H.,et al: "Mitochondrial trifunctional diabetes mellitus:prevalence and clinical characterization of diabetes due to mitochondrial tRNA_<ICU(UUR)> gene mutation in Japanese." Diabetologia. (in press).
[文献書誌] Kamijo T.,et al.: "Mitochodrial protein deficiency:catalytic heterogeneity of the mutant enzyme in two patients." J.Clin.Invest.(in press).
[文献書誌] Tokoro T.,et al.: "Molphological features in hybridmice between two Niemann-Pick disease model mice." Int.J.Dev.Neurosci.(in press).
[文献書誌] Chiba Y.m et al.: "Purufucation and properties of liver holocarboxylase synthetase." Arch.Biochem.Biophys.(in press).
[文献書誌] Yamamoto T.,et al.: "The attenuated elevation of cytoplasmic calcium concentration following low density lipoprotein up take in type C Niemann-Pick fibroblasts." Biochem.Biophys.Research Com.198(2). 438-444 (1994)
[文献書誌] Nakashima.,et al: "Mucopolysaccharidosis IVA:molecular cloning of the human N-acetylgalactosamine 6 sulfatase (GALNS) gene and analysis of the 5′-franking region." Genomics. 20. 99-104 (1994)
[文献書誌] Suzuki et al.: "Novel subtype of peroxisomal acyl-oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein:identification by means of complementation amalvsis." Am.J.Hum.Genet.54. 36-43 (1994)
[文献書誌] Uchiyama A.,et al.: "Identification of a nonsense mutation in ALD protein cDNA from a patient with adrenolikodystrophy." BBRC. 198. 632-636 (1994)
[文献書誌] Yamaguchi S.,et al.: "Biochemical and immunological stydy of seven familiees with 3-ketotiolase deficiency:diagnosis of heterozygotes using immunochemical detetmination of the ratio of mitochondrial acetoacetyl-CoA thiolase protein." Prdiatric Research. 33. 429-433 (1994)
[文献書誌] Sakai N.,et al.: "Krabbe disease:isolation and characterization of a full-length cDNA for human galactocerebrosidase." Biochem.Biophys.Res.Commun.198. 485-491 (1994)
[文献書誌] Kamijo T.,et al.: "Mokecular cloning of the cDNAs for the subunits of rat mitochondrial fatty acid beta-oxidation multienzyme complex.Structural and functional relationships to other mitochondrial and peroxisomal beta-oxidation enzvmes." J.Biol.Chem.268. 26452-26460 (1994)
[文献書誌] 北川照男他: "ゴーシェ病I型6例に対する修飾型フルコセレブロシダーゼ(JCO192)静注療法の多施設治験成績" 小児科臨床. 47. 157-180 (1994)
[文献書誌] Ishihara H.,et al.: "Overexpression of hexokinase I but not GLUT1 glucose transporter alters concentration-dependency of glucose-stimulated insulin secretion in pancrestic b-cell line MLNG." J.Biol.Chem.269. 3081-3087 (1994)
[文献書誌] Ando A.,et al.: "Cloning of a new kinesin-related gene located at Mre centromeric end of Mre human MHC region." Immunogenetics. 39. 194-200 (1994)
[文献書誌] Toyonaga T.,et al.: "Chronic active hepatitis in transgenic mice expressing interferon-gamma in Mre liver." Proc.Natl.Acad.Sci.USA. 91. 614-618 (1994)
[文献書誌] Nobukuni Y.,et al.: "Heterogeneity of mutations in maple syrup urine disease(MSUD):Screening and identification of affected E_1alpha and E_1beta subunits of branched-chain alpha keto acid dehydroxygenase multienzyme complex." Biochem.Biophys.Acta.1225. 64-70 (1993)
[文献書誌] Hoshide R.,et al.: "A specificity of PCR-SSCP for detection of the mutant ornithine transcarbamylase (OTC) gene in patients with OTC deficiency." J.Inher.Metab.Dis.16. 857-862 (1993)
[文献書誌] Hoshide K.,et al.: "Carbamyl phosphate synthetase I deficiency;one base substitution in exon of the CPSI gene causes a 9bp deletion due to aberrant splicing." J.Clin.Invest.91. 1884-1887 (1993)
[文献書誌] Matsuura T.,er al.: "Four novel gene mutation in five Japanese male patients with neonatal or late onset OTC deficiency:Application of PCR-SSCP for all exons and adjacent introns." Human Genet.92. 49-56 (1993)
[文献書誌] Matsuura T.,et al.: "Prenatal monitaring of ornithine transcarbamylase deficiency in two families by DNA analysis." J.Inh.Metab.Dis.16. 31-38 (1993)
[文献書誌] Nakazato H.,et al.: "Identification of a single base insertion in COL4A5 gene in alport syndrome." Kidney Internat.44. 1091-1096 (1993)
[文献書誌] Ohura T.,et al: "The molecular defict in propionic acidemia : exon skipping caused by an 8-bp deletion from an intron tn the PCCB allele." Human Genet.92. 397-402 (1993)
[文献書誌] Aoki M.,et al.: "Mild amyotrophic lateral sclerosis in Japan associated with novel SOD mutation." Nature Genet.5. 323-324 (1993)
[文献書誌] Ida H.,et al.: "Neurotoxity of psychosine in neural cell cultures-thepathogenesi of Krabbe's disease." Jikeikai Med.J.40. 171-179 (1993)
[文献書誌] Ida H.,et al.: "Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme in active." J.Biochem.114. 15-20 (1993)
[文献書誌] Ohashi T.,et al.: "Correction of enzyme deficiency in metachromatic leukodystrophy by retroviral-mediated transfer of the human arylsulfatase A gene." J.Inher.Metab.Dis.16. 881-885 (1993)
[文献書誌] Kawame H.,et al.: "Molecular analysis of Japanese gaucher disease" Human Mutation. 2. 362-367 (1993)
[文献書誌] Hasegawa Y.,et al.: "Mutations in the arylsulfatase A gene of Japanese patients with metachromatic leukodystrophy." DNA and Cell Biology. 12. 493-498 (1993)
[文献書誌] Masuno M.,et al.: "Mucopolysaccharidosis IVA : assignment of the human N acetylgalactosamine 6 sulfate sulfatase (GALNS) gene to chromosome 16q24" Genomics. 16. 777-778 (1993)
[文献書誌] Yamada Y.,et al.: "Mucopolysaccharidosis type II (Hunter desease):13 gene mutations in 52 Japanese patients and carrier detection in four families." Human Genetics. 92. 110-114 (1993)
[文献書誌] Yamaguchi S.,et al.: "Identification of very long chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long chain acyl-CoA dehydrogenase deficiency." Pediatric Research. 34. 111-113 (1993)
[文献書誌] Shimozawa N.,et al.: "Standardization of complememtation grouping of peroxisome-deficient disorders and the second Zellwegerpatient with peroxisomal assembly factor-1(PAF-1)defect." Am.J.Hum.Genet.52. 843-843 (1993)
[文献書誌] Fukao T.,et al.: "Molecular studies of mitochondrial acetoacetyl coenzyme A thiolase deficiency in the two original families." Human Mutation. 2. 214-220 (1993)
[文献書誌] Suzuki Y.,et al.: "Quantative analysis of amniotic fluid pyrimidines for the pronatal diagnosis of hereditary orotic aciduria." J.Inher.Metab.Dis.16. 872-875 (1993)
[文献書誌] Shimozawa N.,et al.: "Prenatal diagnosis of Zwellweger syndrome using DNA analysis." Prenatal diagnosis. 13. 149-149 (1993)
[文献書誌] Toyooka K.,et al.: "Nephrosialidosis : ultrastructural and lectin histochemical study." Acta Neuropathol.86. 198-205 (1993)
[文献書誌] Yamamoto H.,et al.: "Bone marrow-derived osteoclast-like cells from a patient withcraniometaphyseal dysplasialack expression of octeoclast-reactive vacuolar proton pump." J.Clin.Invest.91. 362-367 (1993)
[文献書誌] Tsukamoto H.,et al.: "Different clinical features in monozygotic twins : a case of 7q-syndrome." Clin.Genet.43. 139-142 (1993)
[文献書誌] Kawa-Ha K.,et al.: "Isolation of human herpesvirus 7 from a child with symptoms mimicking chronic Epstein-Barr virus infection." British J.Haemotology.84. 545-548 (1993)
[文献書誌] Tsukamoto H.et al.: "Case of ring chromosome 7 : the first report of neuropathological findings." Am.J.Med.Genet.46. 632-635 (1993)
[文献書誌] 北川照男: "遺伝性代謝病の研究" 学術月報. 46. 521-527 (1993)
[文献書誌] 大和田操他: "先天代謝異常:酵素補充療法(Gauchee病を中心に)" 小児科診療. 56. 49-51 (1993)
[文献書誌] 大和田操他: "テトラヒドロビオプテリン欠乏症の定義と病態" 特殊ミルク情報第26号. 49-51 (1993)
[文献書誌] 大和田操他: "天然性テトラヒドロビオプテリン製剤-ビオプテン顆粒" Molecular Medicine. 30. 512-517 (1993)
[文献書誌] Tsuda M.,et al.: "Molecular analysis of two Japanese cases of denys-drash syndrome." J.Inher.Metab.Dis.16. 876-880 (1993)
[文献書誌] Oka Y.,et al.: "Mitochondrial gene mutation in isler cell antibody-positive diabetics who were initially non-insulin-dependent." Lancet. 342. 527-528 (1993)
[文献書誌] Ishihara H.,et al.: "Pancreatic b-cell line MIN6 exhibits characteriztics of glucose metabolism and glucose-stimulated in secretion similar to those of normal islets." Diabetologia. 36. 1139-1145 (1993)
[文献書誌] Katagiri H.,et al.: "Glucokinase-defictive NIDDM." Lancet. 341. 961-962 (1993)
[文献書誌] Episkopou V.,et al.: "Disruption of the transthyretin gene results in mice with depressed levels of plasma retinal and thyroid hormone." Proc.Natl.Acad.Sci.USA. 90. 2375-2379 (1993)
[文献書誌] Aoyama T.,et al.: "A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase." Biochem.Biophys.Res.Commun. 191. 1369-1372 (1993)
[文献書誌] Yamaguchi S.,et al.: "Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency." Pediatr.Res.34. 111-113 (1993)
[文献書誌] Kanazawa M.,et al.: "Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase." Enzyme Protein. 47. 9-13 (1993)
[文献書誌] Yamamura K.,et al.: "Transgenic mouse model for human genetic diseases." Molec.Reproduc.Develop.36. 248-250 (1993)
[文献書誌] Mausuura T.,et al.: "Four novel gene mutations in five Japanese male patients with neonatal or late onset OTC deficiency : Application of PCR-single-strand conformation polymorphisms for all exons and adjacent introns." Hum.Genet.92. 49-56 (1993)
[文献書誌] 北川照男他: "小児科必修アトラス" 南江堂, 313 (1994)
[文献書誌] 岡田伸太郎: "医学の進歩と社会:脳と発達" 診断と治療社, 1 (1993)
[文献書誌] 乾幸治他: "肝型グリコーゲン病の分子遺伝学:日本臨床" 日本臨床社, 5 (1993)
[文献書誌] 島田和典他: "「分子病理学-疾病の分子機構」杉山武敏編" 文光堂, 5 (1993)
[文献書誌] 前田秀一郎他: "「遺伝子病入門」高久史麿他編" 南江堂, 17 (1993)

1993 年度 実績報告書

単一遺伝子病の分子・細胞生物学的研究、疾患発症の分子機構の解明

研究代表者

松田 一郎 熊本大学, 医学部, 教授 (10000986)

研究成果

[文献書誌] Horie K,et al.: "Structure of replacement vectors for efficient gene targeting." J.Biochem.(Tokyo). (in press).

[文献書誌] Nomura M.,et al.: "Isolation and characterization of retinoic acid inducible cDNA clones in F9 cells:One of the early inducible clones encodes oa novel protein sharing several highly homologus regions with a Drosophila polyhomcotic protein" Differentiation. (in press).

[文献書誌] Horie K.,et al.: "Gene targeting by vector with hairpin-shaped oligonucleotide caps." Biochem.Mol.Bio.Internatl.(in press).

[文献書誌] Katagiri H.,et al: "Mitochondrial trifunctional diabetes mellitus:prevalence and clinical characterization of diabetes due to mitochondrial tRNA_<ICU(UUR)> gene mutation in Japanese." Diabetologia. (in press).

[文献書誌] Kamijo T.,et al.: "Mitochodrial protein deficiency:catalytic heterogeneity of the mutant enzyme in two patients." J.Clin.Invest.(in press).

[文献書誌] Tokoro T.,et al.: "Molphological features in hybridmice between two Niemann-Pick disease model mice." Int.J.Dev.Neurosci.(in press).

[文献書誌] Chiba Y.m et al.: "Purufucation and properties of liver holocarboxylase synthetase." Arch.Biochem.Biophys.(in press).

[文献書誌] Yamamoto T.,et al.: "The attenuated elevation of cytoplasmic calcium concentration following low density lipoprotein up take in type C Niemann-Pick fibroblasts." Biochem.Biophys.Research Com.198(2). 438-444 (1994)

[文献書誌] Nakashima.,et al: "Mucopolysaccharidosis IVA:molecular cloning of the human N-acetylgalactosamine 6 sulfatase (GALNS) gene and analysis of the 5′-franking region." Genomics. 20. 99-104 (1994)

[文献書誌] Suzuki et al.: "Novel subtype of peroxisomal acyl-oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein:identification by means of complementation amalvsis." Am.J.Hum.Genet.54. 36-43 (1994)

[文献書誌] Uchiyama A.,et al.: "Identification of a nonsense mutation in ALD protein cDNA from a patient with adrenolikodystrophy." BBRC. 198. 632-636 (1994)

[文献書誌] Yamaguchi S.,et al.: "Biochemical and immunological stydy of seven familiees with 3-ketotiolase deficiency:diagnosis of heterozygotes using immunochemical detetmination of the ratio of mitochondrial acetoacetyl-CoA thiolase protein." Prdiatric Research. 33. 429-433 (1994)

[文献書誌] Sakai N.,et al.: "Krabbe disease:isolation and characterization of a full-length cDNA for human galactocerebrosidase." Biochem.Biophys.Res.Commun.198. 485-491 (1994)

[文献書誌] Kamijo T.,et al.: "Mokecular cloning of the cDNAs for the subunits of rat mitochondrial fatty acid beta-oxidation multienzyme complex.Structural and functional relationships to other mitochondrial and peroxisomal beta-oxidation enzvmes." J.Biol.Chem.268. 26452-26460 (1994)

[文献書誌] 北川照男 他: "ゴーシェ病I型6例に対する修飾型フルコセレブロシダーゼ(JCO192)静注療法の多施設治験成績" 小児科臨床. 47. 157-180 (1994)

[文献書誌] Ishihara H.,et al.: "Overexpression of hexokinase I but not GLUT1 glucose transporter alters concentration-dependency of glucose-stimulated insulin secretion in pancrestic b-cell line MLNG." J.Biol.Chem.269. 3081-3087 (1994)

[文献書誌] Ando A.,et al.: "Cloning of a new kinesin-related gene located at Mre centromeric end of Mre human MHC region." Immunogenetics. 39. 194-200 (1994)

[文献書誌] Toyonaga T.,et al.: "Chronic active hepatitis in transgenic mice expressing interferon-gamma in Mre liver." Proc.Natl.Acad.Sci.USA. 91. 614-618 (1994)

[文献書誌] Nobukuni Y.,et al.: "Heterogeneity of mutations in maple syrup urine disease(MSUD):Screening and identification of affected E_1alpha and E_1beta subunits of branched-chain alpha keto acid dehydroxygenase multienzyme complex." Biochem.Biophys.Acta.1225. 64-70 (1993)

[文献書誌] Hoshide R.,et al.: "A specificity of PCR-SSCP for detection of the mutant ornithine transcarbamylase (OTC) gene in patients with OTC deficiency." J.Inher.Metab.Dis.16. 857-862 (1993)

[文献書誌] Hoshide K.,et al.: "Carbamyl phosphate synthetase I deficiency;one base substitution in exon of the CPSI gene causes a 9bp deletion due to aberrant splicing." J.Clin.Invest.91. 1884-1887 (1993)

[文献書誌] Matsuura T.,er al.: "Four novel gene mutation in five Japanese male patients with neonatal or late onset OTC deficiency:Application of PCR-SSCP for all exons and adjacent introns." Human Genet.92. 49-56 (1993)

[文献書誌] Matsuura T.,et al.: "Prenatal monitaring of ornithine transcarbamylase deficiency in two families by DNA analysis." J.Inh.Metab.Dis.16. 31-38 (1993)

[文献書誌] Nakazato H.,et al.: "Identification of a single base insertion in COL4A5 gene in alport syndrome." Kidney Internat.44. 1091-1096 (1993)

[文献書誌] Ohura T.,et al: "The molecular defict in propionic acidemia : exon skipping caused by an 8-bp deletion from an intron tn the PCCB allele." Human Genet.92. 397-402 (1993)

[文献書誌] Aoki M.,et al.: "Mild amyotrophic lateral sclerosis in Japan associated with novel SOD mutation." Nature Genet.5. 323-324 (1993)

[文献書誌] Ida H.,et al.: "Neurotoxity of psychosine in neural cell cultures-thepathogenesi of Krabbe's disease." Jikeikai Med.J.40. 171-179 (1993)

[文献書誌] Ida H.,et al.: "Cloning of a human acid sphingomyelinase cDNA with a new mutation that renders the enzyme in active." J.Biochem.114. 15-20 (1993)

[文献書誌] Ohashi T.,et al.: "Correction of enzyme deficiency in metachromatic leukodystrophy by retroviral-mediated transfer of the human arylsulfatase A gene." J.Inher.Metab.Dis.16. 881-885 (1993)

[文献書誌] Kawame H.,et al.: "Molecular analysis of Japanese gaucher disease" Human Mutation. 2. 362-367 (1993)

[文献書誌] Hasegawa Y.,et al.: "Mutations in the arylsulfatase A gene of Japanese patients with metachromatic leukodystrophy." DNA and Cell Biology. 12. 493-498 (1993)

[文献書誌] Masuno M.,et al.: "Mucopolysaccharidosis IVA : assignment of the human N acetylgalactosamine 6 sulfate sulfatase (GALNS) gene to chromosome 16q24" Genomics. 16. 777-778 (1993)

[文献書誌] Yamada Y.,et al.: "Mucopolysaccharidosis type II (Hunter desease):13 gene mutations in 52 Japanese patients and carrier detection in four families." Human Genetics. 92. 110-114 (1993)

[文献書誌] Yamaguchi S.,et al.: "Identification of very long chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long chain acyl-CoA dehydrogenase deficiency." Pediatric Research. 34. 111-113 (1993)

[文献書誌] Shimozawa N.,et al.: "Standardization of complememtation grouping of peroxisome-deficient disorders and the second Zellwegerpatient with peroxisomal assembly factor-1(PAF-1)defect." Am.J.Hum.Genet.52. 843-843 (1993)

[文献書誌] Fukao T.,et al.: "Molecular studies of mitochondrial acetoacetyl coenzyme A thiolase deficiency in the two original families." Human Mutation. 2. 214-220 (1993)

[文献書誌] Suzuki Y.,et al.: "Quantative analysis of amniotic fluid pyrimidines for the pronatal diagnosis of hereditary orotic aciduria." J.Inher.Metab.Dis.16. 872-875 (1993)

[文献書誌] Shimozawa N.,et al.: "Prenatal diagnosis of Zwellweger syndrome using DNA analysis." Prenatal diagnosis. 13. 149-149 (1993)

[文献書誌] Toyooka K.,et al.: "Nephrosialidosis : ultrastructural and lectin histochemical study." Acta Neuropathol.86. 198-205 (1993)

[文献書誌] Yamamoto H.,et al.: "Bone marrow-derived osteoclast-like cells from a patient withcraniometaphyseal dysplasialack expression of octeoclast-reactive vacuolar proton pump." J.Clin.Invest.91. 362-367 (1993)

[文献書誌] Tsukamoto H.,et al.: "Different clinical features in monozygotic twins : a case of 7q-syndrome." Clin.Genet.43. 139-142 (1993)

[文献書誌] Kawa-Ha K.,et al.: "Isolation of human herpesvirus 7 from a child with symptoms mimicking chronic Epstein-Barr virus infection." British J.Haemotology.84. 545-548 (1993)

[文献書誌] Tsukamoto H.et al.: "Case of ring chromosome 7 : the first report of neuropathological findings." Am.J.Med.Genet.46. 632-635 (1993)

[文献書誌] 北川照男: "遺伝性代謝病の研究" 学術月報. 46. 521-527 (1993)

[文献書誌] 大和田操 他: "先天代謝異常:酵素補充療法(Gauchee病を中心に)" 小児科診療. 56. 49-51 (1993)

[文献書誌] 大和田操 他: "テトラヒドロビオプテリン欠乏症の定義と病態" 特殊ミルク情報第26号. 49-51 (1993)

[文献書誌] 大和田操 他: "天然性テトラヒドロビオプテリン製剤-ビオプテン顆粒" Molecular Medicine. 30. 512-517 (1993)

[文献書誌] Tsuda M.,et al.: "Molecular analysis of two Japanese cases of denys-drash syndrome." J.Inher.Metab.Dis.16. 876-880 (1993)

[文献書誌] Oka Y.,et al.: "Mitochondrial gene mutation in isler cell antibody-positive diabetics who were initially non-insulin-dependent." Lancet. 342. 527-528 (1993)

[文献書誌] Ishihara H.,et al.: "Pancreatic b-cell line MIN6 exhibits characteriztics of glucose metabolism and glucose-stimulated in secretion similar to those of normal islets." Diabetologia. 36. 1139-1145 (1993)

[文献書誌] Katagiri H.,et al.: "Glucokinase-defictive NIDDM." Lancet. 341. 961-962 (1993)

[文献書誌] Episkopou V.,et al.: "Disruption of the transthyretin gene results in mice with depressed levels of plasma retinal and thyroid hormone." Proc.Natl.Acad.Sci.USA. 90. 2375-2379 (1993)

[文献書誌] Aoyama T.,et al.: "A novel disease with deficiency of mitochondrial very-long-chain acyl-CoA dehydrogenase." Biochem.Biophys.Res.Commun. 191. 1369-1372 (1993)

[文献書誌] Yamaguchi S.,et al.: "Identification of very-long-chain acyl-CoA dehydrogenase deficiency in three patients previously diagnosed with long-chain acyl-CoA dehydrogenase deficiency." Pediatr.Res.34. 111-113 (1993)

[文献書誌] Kanazawa M.,et al.: "Molecular cloning and sequence analysis of the cDNA for human mitochondrial short-chain enoyl-CoA hydratase." Enzyme Protein. 47. 9-13 (1993)

[文献書誌] Yamamura K.,et al.: "Transgenic mouse model for human genetic diseases." Molec.Reproduc.Develop.36. 248-250 (1993)

[文献書誌] Mausuura T.,et al.: "Four novel gene mutations in five Japanese male patients with neonatal or late onset OTC deficiency : Application of PCR-single-strand conformation polymorphisms for all exons and adjacent introns." Hum.Genet.92. 49-56 (1993)

[文献書誌] 北川照男 他: "小児科必修アトラス" 南江堂, 313 (1994)

[文献書誌] 岡田伸太郎: "医学の進歩と社会:脳と発達" 診断と治療社, 1 (1993)

[文献書誌] 乾幸治 他: "肝型グリコーゲン病の分子遺伝学:日本臨床" 日本臨床社, 5 (1993)

[文献書誌] 島田和典 他: "「分子病理学-疾病の分子機構」 杉山武敏編" 文光堂, 5 (1993)

[文献書誌] 前田秀一郎 他: "「遺伝子病入門」高久史麿 他 編" 南江堂, 17 (1993)

1993 年度実績報告書

松田一郎熊本大学, 医学部, 教授 (10000986)

[文献書誌] 北川照男他: "ゴーシェ病I型6例に対する修飾型フルコセレブロシダーゼ(JCO192)静注療法の多施設治験成績" 小児科臨床. 47. 157-180 (1994)

[文献書誌] 大和田操他: "先天代謝異常:酵素補充療法(Gauchee病を中心に)" 小児科診療. 56. 49-51 (1993)

[文献書誌] 大和田操他: "テトラヒドロビオプテリン欠乏症の定義と病態" 特殊ミルク情報第26号. 49-51 (1993)

[文献書誌] 大和田操他: "天然性テトラヒドロビオプテリン製剤-ビオプテン顆粒" Molecular Medicine. 30. 512-517 (1993)

[文献書誌] 北川照男他: "小児科必修アトラス" 南江堂, 313 (1994)

[文献書誌] 乾幸治他: "肝型グリコーゲン病の分子遺伝学:日本臨床" 日本臨床社, 5 (1993)

[文献書誌] 島田和典他: "「分子病理学-疾病の分子機構」杉山武敏編" 文光堂, 5 (1993)

[文献書誌] 前田秀一郎他: "「遺伝子病入門」高久史麿他編" 南江堂, 17 (1993)