Research Papers

Publications and cited

Until 1995, we contributed to early detection of rare diseases in Japan through organic acid analysis using gas chromatography-mass spectrometry. Based on that experience, we have launched innovative diagnostic support called metabolomics earliest in the world.

Mass Spectrom Rev. 1996; 15: 43-57 is cited as the most advanced application of metabolomics, in papers written by remarkable overseas researchers who lead the world at the forefront of metabolomics.

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

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

English Research Papers List 1996 or later

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.

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.