研究論文・リンク
1996年以降の、主にメタボローム解析に関する論文を日本疾患メタボローム解析研究所のホームページに公開しました。それ以前は有機酸分析をとおしてわが国の希少疾患の早期発見に貢献しました。有機酸分析の経験と実績をもとに、メタボローム解析という革新的な診断支援を世界で最も早い時期に開始しています。
1996年に発表した下記の論文は最も進んだメタボロームの応用研究として、メタボロームの最前線で世界をリードした著明な海外の研究者の論文で引用されています。下記2論文はドイツのメタボローム研究のメッカ、Max Plank 研究所の論文です。
A new
chemical diagnostic method for inborn errors of metabolism by
mass spectrometry-rapid, practical, and simultaneous urinary
metabolites analysis.
Matsumoto I, Kuhara T.
Mass Spectrom Rev. 1996;15(1):43-57.
Metabolic profiling: a Rosetta Stone for genomics?
RN Trethewey, AJ Krotzky, L Willmitzert- Current Opinion in Plant Biology, 1999 - Elsevier
Man has always aspired to understand the nature of life and the chances of achieving this, at least at the molecular level, have never looked better. As a technology-driven revolution sweeps through the life sciences and we are submerged in an avalanche of new information…Metabolic profiling allows comprehensive phenotyping of genetically or environmentally modified plant systems
U Roessner, A Luedemann, D Brust, O Fiehn… The Plant…, 2001 - Am Soc Plant Biol
Metabolic profiling using gas chromatography?mass spectrometry technologies is a technique whose potential in the field of functional genomics is largely untapped. To demonstrate the general usefulness of this technique, we applied to diverse plant genotypes…
Furthermore
Google Scholar Matsumoto I, Kuhara T：Mass Spectrom Rev.1996
2005年に発表した下記の論文も、米国Food and Drug Administration (FDA) の研究者等のメタボローム研究の最前線で世界をリードする著明な海外の研究者の論文に引用されています。
Gas
chromatographic-mass spectrometric urinary metabolome analysis to
study mutations of inborn errors of metabolism.
Kuhara T.
Mass Spectrom Rev. 2005 Nov-Dec;24(6):814-27.
Global metabolic profiling and its role in systems biology to advance personalized medicine in the 21st century
LK Schnackenberg- Expert Review of Molecular Diagnostics, 2007 - Taylor & Francis
Systems biology attempts to elucidate the complex interaction between genes, proteins and metabolites to provide a mechanistic understanding of cellular function and how this function is affected by disease processes, drug toxicity or drug efficacy effects. Global metabolic …Metabolomic biomarkers: their role in the critical path
LK Schnackenberg, RD Beger- Drug Discovery Today: Technologies, 2007 - Elsevier
Global metabolic profiling is being applied to identify biomarkers of health. Some small molecules are exquisitely sensitive indicators of health status. Metabolic profiling analyses are being used to determine biomarkers of drug safety and effectiveness as well as disease…Mass spectrometry‐based metabolomics
K Dettmer, PA Aronov…Mass spectrometry…, 2007 - Wiley Online Library
This review presents an overview of the dynamically developing field of mass spectrometry-based metabolomics. Metabolomics aims at the comprehensive and quantitative analysis of wide arrays of metabolites in biological samples. These numerous analytes have very …
Furthermore
Google Scholar Kuhara T：Mass Spectrom Rev. 2005
英論文リスト1996以降
A new
chemical diagnostic method for inborn errors of metabolism by
mass spectrometry-rapid, practical, and simultaneous urinary
metabolites analysis.
Matsumoto I, Kuhara T.
Mass Spectrom Rev. 1996;15(1):43-57.
Gas
chromatographic-mass spectrometric metabolic profiling of
patients with fatal infantile mitochondrial myopathy with de Toni-Fanconi-Debré
syndrome.
Ning C, Kuhara T, Inoue Y, Zhang CH, Matsumoto M, Shinka T,
Furumoto T, Yokota K, Matsumoto I.
Acta Paediatr Jpn. 1996 Dec;38(6):661-6.
Mild
form of beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA
thiolase deficiency) in two Japanese siblings: identification of
detectable residual activity and cross-reactive material in EB-transformed
lymphocytes.
Fukao T, Kodama A, Aoyanagi N, Tsukino R, Uemura S, Song XQ,
Watanebe H, Kuhara T, Matsumoto I, Orii T, Kondo N.
Clin Genet. 1996 Oct;50(4):263-6.
Family
study of 2,8-dihydroxyadenine stone formation: report of two
cases of a compound heterozygote for adenine
phosphoribosyltransferase deficiency (APRT*J/APRT*Q0).
Suzuki K, Kobayashi S, Kawamura K, Kuhara T, Tsugawa R.
Int J Urol. 1997 May;4(3):304-6.
Mitochondrial
trifunctional protein deficiency associated with recurrent
myoglobinuria in adolescence.
Miyajima H, Orii KE, Shindo Y, Hashimoto T, Shinka T, Kuhara T,
Matsumoto I, Shimizu H, Kaneko E.
Neurology. 1997 Sep;49(3):833-7.
An
asymptomatic infant with isolated 3-methylcrotonyl-coenzyme: a
carboxylase deficiency detected by newborn screening for maple
syrup urine disease.
Ihara K, Kuromaru R, Inoue Y, Kuhara T, Matsumoto I,
Yoshino M, Fukushige J.
Eur J Pediatr. 1997 Sep;156(9):713-5.
Successful
treatment by direct hemoperfusion of coma possibly resulting from
mitochondrial dysfunction in acute valproate intoxication.
Matsumoto J, Ogawa H, Maeyama R, Okudaira K, Shinka T, Kuhara
T, Matsumoto I.
Epilepsia. 1997 Aug;38(8):950-3.
Pilot
study of gas chromatographic-mass spectrometric screening of
newborn urine for inborn errors of metabolism after treatment
with urease.
Kuhara T, Shinka T, Inoue Y, Ohse M, Zhen-wei X, Yoshida I,
Inokuchi T, Yamaguchi S, Takayanagi M, Matsumoto I.
J Chromatogr B Biomed Sci Appl. 1999 Aug 6;731(1):141-7.
A study
on alpha-ketoadipic aciduria by gas chromatographic-mass
spectrometry.
Xia ZW, Inoue Y, Ohse M, Shinka T, Kuhara T.
World J Gastroenterol. 2000 Oct;6(5):766-769.
Diagnosis
of inborn errors of metabolism using filter paper urine, urease
treatment, isotope dilution and gas chromatography-mass
spectrometry.
Kuhara T.
J Chromatogr B Biomed Sci Appl. 2001 Jul 5;758(1):3-25. Review.
Simple
gas chromatographic-mass spectrometric procedure for diagnosing
pyrimidine degradation defects for prevention of severe
anticancer side effects.
Kuhara T, Ohdoi C, Ohse M.
J Chromatogr B Biomed Sci Appl. 2001 Jul 5;758(1):61-74.
Diagnosis
of Japanese patients with HHH syndrome by molecular genetic
analysis: a common mutation, R179X.
Miyamoto T, Kanazawa N, Kato S, Kawakami M, Inoue Y, Kuhara T,
Inoue T, Takeshita K, Tsujino S.
J Hum Genet. 2001;46(5):260-2.
Diagnosis
and monitoring of inborn errors of metabolism using urease-pretreatment
of urine, isotope dilution, and gas chromatography-mass
spectrometry.
Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Dec 5;781(1-2):497-517.
Screening
and diagnosis of beta-ureidopropionase deficiency by gas
chromatographic/mass spectrometric analysis of urine.
Ohse M, Matsuo M, Ishida A, Kuhara T.
J Mass Spectrom. 2002 Sep;37(9):954-62.
Screening
and diagnosis of beta-ureidopropionase deficiency by gas
chromatographic/mass spectrometric analysis of urine.
Ohse M, Matsuo M, Ishida A, Kuhara T.
J Mass Spectrom. 2002 Sep;37(9):954-62.
Unexpectedly
high prevalence of the mild form of propionic acidemia in Japan:
presence of a common mutation and possible clinical implications.
Yorifuji T, Kawai M, Muroi J, Mamada M, Kurokawa K, Shigematsu Y,
Hirano S, Sakura N, Yoshida I, Kuhara T, Endo F,
Mitsubuchi H, Nakahata T.
Hum Genet. 2002 Aug;111(2):161-5.
Rapid
and sensitive method for prenatal diagnosis of propionic acidemia
using stable isotope dilution gas chromatography-mass
spectrometry and urease pretreatment.
Inoue Y, Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Aug 25;776(1):71-7.
Rapid
and sensitive detection of urinary 4-hydroxybutyric acid and its
related compounds by gas chromatography-mass spectrometry in a
patient with succinic semialdehyde dehydrogenase deficiency.
Shinka T, Inoue Y, Ohse M, Ito A, Ohfu M, Hirose S, Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2002 Aug 25;776(1):57-63.
Gas
chromatographic-mass spectrometric newborn screening for
propionic acidaemia by targeting methylcitrate in dried filter-paper
urine samples.
Kuhara T, Ohse M, Inoue Y, Yorifuji T, Sakura N,
Mitsubuchi H, Endo F, Ishimatu J.
J Inherit Metab Dis. 2002 May;25(2):98-106.
Chemical
diagnosis of Lesch-Nyhan syndrome using gas chromatography-mass
spectrometry detection.
Ohdoi C, Nyhan WL, Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 15;792(1):123-30.
Rapid
gas chromatographic-mass spectrometric diagnosis of
dihydropyrimidine dehydrogenase deficiency and
dihydropyrimidinase deficiency.
Kuhara T, Ohdoi C, Ohse M, van Kuilenburg AB, van Gennip
AH, Sumi S, Ito T, Wada Y, Matsumoto I.
J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 15;792(1):107-15.
Effect
of valproic acid on the urinary metabolic profile of a patient
with succinic semialdehyde dehydrogenase deficiency.
Shinka T, Ohfu M, Hirose S, Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 15;792(1):99-106.
Monitoring
method for pre- and post-liver transplantation in patients with
primary hyperoxaluria type I.
Inoue Y, Masuyama H, Ikawa H, Mitsubuchi H, Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Jul 15;792(1):89-97.
Gas
chromatographic-mass spectrometric urinary metabolome analysis to
study mutations of inborn errors of metabolism.
Kuhara T.
Mass Spectrom Rev. 2005 Nov-Dec;24(6):814-27.
Rapid
and sensitive screening for and chemical diagnosis of Canavan
disease by gas chromatography-mass spectrometry.
Inoue Y, Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2004 Jun 25;806(1):33-9.
Differential
chemical diagnosis of primary hyperoxaluria type II. Highly
sensitive analysis of optical isomers of glyceric acid by GC/MS
as diastereoisomeric derivatives.
Inoue Y, Shinka T, Ohse M, Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Aug 25;823(1):2-6.
Acute
encephalopathy associated with influenza virus infection in a
patient with hyperprolinaemia type II.
Kato Y, Ihara K, Miyako K, Kuhara T, Inoue Y, Hara T.
J Inherit Metab Dis. 2005;28(5):789-90.
Biotin
deficiency in an infant fed with amino acid formula.
Fujimoto W, Inaoki M, Fukui T, Inoue Y, Kuhara T.
J Dermatol. 2005 Apr;32(4):256-61.
Noninvasive
human metabolome analysis for differential diagnosis of inborn
errors of metabolism.
Kuhara T.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Aug;855(1):42-50.
Five
cases of beta-ureidopropionase deficiency detected by GC/MS
analysis of urine metabolome.
Kuhara T, Ohse M, Inoue Y, Shinka T.
J Mass Spectrom. 2009 Feb;44(2):214-21
Quiz
page June 2009: worsening kidney function with a history of
urolithiasis.
Kimura T, Yasuda K, Obi Y, Kobayashi K, Kuhara T, Isaka Y,
Imai E, Rakugi H, Hayashi T.
Am J Kidney Dis. 2009 Jun;53(6):A37-9.
Urinary
metabolic profile of phenylketonuria in patients receiving total
parenteral nutrition and medication.
Kuhara T, Ohse M, Inoue Y, Shinka T, Okano Y, Shintaku H,
Hongou K, Miyawaki T, Morinobu W, Tamai H, Omura K.
Rapid Commun Mass Spectrom. 2009 Oct;23(19):3167-72
Urinary
2-hydroxy-5-oxoproline, the lactam form of α-ketoglutaramate, is
markedly increased in urea cycle disorders.
Kuhara T, Inoue Y, Ohse M, Krasnikov BF, Cooper AJ.
Anal Bioanal Chem. 2011 Jun;400(7):1843-51.
Metabolomic
analysis reveals hepatic metabolite perturbations in citrin/mitochondrial
glycerol-3-phosphate dehydrogenase double-knockout mice, a model
of human citrin deficiency.
Saheki T, Inoue K, Ono H, Tushima A, Katsura N, Yokogawa M,
Yoshidumi Y, Kuhara T, Ohse M, Eto K, Kadowaki T, Sinasac
DS, Kobayashi K.
Mol Genet Metab. 2011 Dec;104(4):492-500.
A GC/MS-based
metabolomic approach for diagnosing citrin deficiency.
Kuhara T, Ohse M, Inoue Y, Cooper AJ.
Anal Bioanal Chem. 2011 Jun;400(7):1881-94.
Contiguous
deletion of SLC6A8 and BAP31 in a patient with severe dystonia
and sensorineural deafness.
Osaka H, Takagi A, Tsuyusaki Y, Wada T, Iai M, Yamashita S,
Shimbo H, Saitsu H, Salomons GS, Jakobs C, Aida N, Toshihiro S, Kuhara
T, Matsumoto N.
Mol Genet Metab. 2012 May;106(1):43-7.
Ethnic
differences in GRHPR mutations in patients with primary
hyperoxaluria type 2.
Takayama T, Takaoka N, Nagata M, Johnin K, Okada Y, Tanaka S,
Kawamura M, Inokuchi T, Ohse M, Kuhara T, Tanioka F,
Yamada H, Sugimura H, Ozono S.
Clin Genet. 2014 Oct;86(4):342-8.
SSADH
deficiency possibly associated with enzyme activity-reducing SNPs.
Akiyama T, Osaka H, Shimbo H, Kuhara T, Shibata T,
Kobayashi K, Kurosawa K, Yoshinaga H.
Brain Dev. 2016 Oct;38(9):871-4.
Calcified
nodules on fingers in primary hyperoxaluria type 2.
Yamanouchi M, Ubara Y, Takayama T, Kuhara T, Takaichi K.
Lancet Diabetes Endocrinol. 2016 May;4(5):468.
A
Japanese case of β-ureidopropionase deficiency with dysmorphic
features.
Akiyama T, Shibata T, Yoshinaga H, Kuhara T, Nakajima Y,
Kato T, Maeda Y, Ohse M, Oka M, Kageyama M, Kobayashi K.
Brain Dev. 2017 Jan;39(1):58-61. doi: 10.1016/j.braindev.2016.08.001.
Epub 2016 Aug 21.
Nit1 is
a metabolite repair enzyme that hydrolyzes deaminated glutathione.
Peracchi A, Veiga-da-Cunha M, Kuhara T, Ellens KW, Paczia
N, Stroobant V, Seliga AK, Marlaire S, Jaisson S, Bommer GT, Sun
J, Huebner K, Linster CL, Cooper AJL, Van Schaftingen E.
Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3233-E3242.
〔研究〕論文発表
〔研究〕 論文発表 Published online before print April 3, 2017
Nit1 is a metabolite repair enzyme that hydrolyzes deaminated glutathione
Alessio Peracchi, Maria Veiga-da-Cunha, Tomiko Kuhara, Arthur J. L. Cooper, and Emile Van Schaftingen
http://www.pnas.org/content/early/2017/03/29/1613736114.abstract
最も魅力的な機能未知遺伝子トップ１０のひとつ、Nit 1に関する論文です。当研究所のメタボロミクスの用途は広く、機能未知遺伝子の機能解明にも役立ちます。本論文のような生命科学の基礎研究や創薬のあらゆる段階での研究に利用できます。
兼六園 新緑