Asian Science Citation Index is committed to provide an authoritative, trusted and significant information by the coverage of the most important and influential journals to meet the needs of the global scientific community.  
ASCI Database
308-Lasani Town,
Sargodha Road,
Faisalabad, Pakistan
Fax: +92-41-8815544
Contact Via Web
Suggest a Journal
Articles by M Kato
Total Records ( 6 ) for M Kato
  K Ogino , M Kato , Y Furuse , Y Kinugasa , K Ishida , S Osaki , T Kinugawa , O Igawa , I Hisatome , C Shigemasa , S. D Anker and W. Doehner

Background— Hyperuricemia is common in chronic heart failure (CHF), and it is a strong independent marker of prognosis. Upregulated xanthine oxidase (XO) activity and impaired renal excretion have been shown to account for increased serum uric acid (UA) levels in CHF. Therapeutic interventions with allopurinol to reduce UA levels by XO inhibition have been shown to be beneficial. Discussions are ongoing whether UA itself is actively involved or it is a mere marker of upregulated XO activity within CHF pathophysiology. Therefore, the aim of this study was to test the effect of lowering UA by uricosuric treatment without XO inhibition on hemodynamic and metabolic characteristics of CHF. Impaired renal excretion of UA was taken into account.

Methods and Results— Serum UA (SUA), urinary UA (uUA) excretion, and renal clearance test for UA (ClUA) were measured in 82 patients with CHF. SUA was significantly increased compared with controls of similar age (control, 5.45±0.70 mg/dL; New York Heart Association I, 6.48±1.70 mg/dL; New York Heart Association II, 7.34±1.94 mg/dL; New York Heart Association III, 7.61±2.11 mg/dL; P<0.01). Patients with CHF showed lower uUA excretion and ClUA. On multivariate analysis, insulin, brain natriuretic peptide (P<0.01), and creatinine levels (P=0.05) showed independent correlation with SUA. The treatment effect of the uricosuric agent benzbromarone was tested in 14 patients with CHF with hyperuricemia in a double-blind, placebo-controlled, randomized crossover study design. Benzbromarone significantly decreased SUA (P<0.01). Brain natriuretic peptide, left ventricular ejection fraction, and dimensions in echocardiographic assessment did not change after benzbromarone therapy. In contrast, fasting insulin (placebo, 18.8±8.9 µU/mL; benzbromarone, 11.0±6.2 µU/mL; P<0.05), homeostasis model assessment of insulin resistance index (placebo, 5.4±2.6; benzbromarone, 3.0±1.7; P<0.05), and tumor necrosis factor- (placebo, 2.59±0.63 pg/mL; benzbromarone, 2.14±0.51 pg/mL; P<0.05) improved after benzbromarone, and the changes in tumor necrosis factor- levels were correlated with reduction of SUA (P<0.05).

Conclusions— These results show that UA lowering without XO inhibition may not have an effect on hemodynamic impairment in CHF pathophysiology. To the extent that these data are correct, this finding suggests that upregulated XO activity rather than UA itself is actively involved in hemodynamic impairment in CHF.

Clinical Trial Registration— clinical Identifier: NCT00422318.

  N Hosono , M Kato , K Kiyotani , T Mushiroda , S Takata , H Sato , H Amitani , Y Tsuchiya , K Yamazaki , T Tsunoda , H Zembutsu , Y Nakamura and M. Kubo

Background: Cytochrome P450 2D6 (CYP2D6), one of the most important drug-metabolizing enzymes, has been reported to possess variation in the encoding CYP2D6 gene (cytochrome P450, family 2, subfamily D, polypeptide 6) that affects enzymatic activity. For the pharmacogenetic study of CYP2D6, accurate measurement of the dosage of the functional gene is essential; however, current genotyping techniques are insufficient because of their inability to provide the exact copy number of functional CYP2D6 genes.

Methods: We developed 3 quantitative real-time PCR (qPCR) assays for estimating the total copy number of the CYP2D6 gene, as well as 24-multiplex PCR-based real-time Invader assays (mPCR-RETINAs) for estimating the allele ratio at each variation locus. After determining the allele copy number at each locus, we estimated the frequencies of CYP2D6 alleles in a population and the diplotype in each individual by a CNVphaser (copy number variation phaser). The qPCR assays and RETINAs used for HapMap Japanese and Chinese samples were applied to 455 Japanese individuals.

Results: Forty-two individuals (9.2%) had one CYP2D6 gene copy, 207 (45.5%) had 2 copies, 161 (35.4%) had 3 copies, 40 (8.8%) had 4 copies, and 5 (1.1%) had 5 copies of the CYP2D6 gene. We found 16 different CYP2D6 alleles, with frequencies similar to those described in previous reports. In the diplotype analysis, we observed that CYP2D6*1/*1 and *1/*10-*36 were the most common diplotypes (approximately 20%) in our population.

Conclusions: Our method is the first to determine the exact number of functional CYP2D6 gene copies. We believe our method will facilitate and accelerate the detailed pharmacogenetic analysis of CYP2D6.

  M Kato , L Arce and R. Natarajan

MicroRNAs (miRs) are a family of short non-coding RNAs. These endogenously produced factors have been shown to play important roles in gene regulation. The discovery of miRs has greatly expanded our knowledge of gene regulation at the posttranscriptional level. miRs inhibit target gene expression by blocking protein translation or by inducing mRNA degradation and therefore have the potential to modulate physiologic and pathologic processes. The imperative need to determine their cellular targets and disease relevance has sparked an unprecedented explosion of research in the miR field. Recent findings have revealed critical functions for specific miRs in cellular events such as proliferation, differentiation, development, and immune responses and in the regulation of genes relevant to human diseases. Of particular interest to renal researchers are recent reports that key miRs are highly expressed in the kidney and can act as effectors of TGF-β actions and high glucose in diabetic kidney disease. Moreover, podocyte-specific deletion of Dicer, a key enzyme involved in miR biogenesis, led to proteinuria and severe renal dysfunction in mice. Hence, studies aimed at determining the in vitro and in vivo functions of miRs in the kidney could determine their value as therapeutic targets for progressive renal glomerular and tubular diseases. Translational approaches could be facilitated by the development of effective inhibitors of specific miRs and methods for optimal delivery of anti-miRs to the kidney. The major goal of this review is to highlight key functions of these miRs and their relationships to human diseases, with special emphasis on diabetic kidney disease.

  M Kato and Y. Honjo

This article explores the persistence of market leadership in Japanese manufacturing industries over the period 1975–2004. By applying survival data techniques, we examine how long market leadership persists and how the duration of market leadership varies according to industry-specific characteristics. Our findings indicate that market leaders maintain their leadership positions for, on average, 20 years from 1975 in Japanese manufacturing industries. We provide evidence that market leadership tends to persist in capital-intensive and legally cartelized industries, whereas it is less likely to persist in demand-volatile, R&D-intensive, and import-intensive industries.

  N Adachi , N Akanuma , M Ito , M Kato , T Hara , Y Oana , M Matsuura , Y Okubo and T. Onuma


Age at the first psychotic episode and an interval between the onset of epilepsy and that of psychosis reflect developmental processes of interictal psychosis. However, factors relating to these indices remain unknown.


To identify clinical variables that are associated with the timing of the development of interictal psychosis.


In 285 adults with epilepsy with interictal psychosis, effects of epileptic (epilepsy type), organic (intellectual functioning) and genetic (family history of psychosis) variables on timing of the development of psychosis were examined.


The mean interval between the onset of epilepsy and that of psychosis was 14.4 years. Some psychosis occurred within a few years of the first seizure. Generalised epilepsy, normal intellectual function and a positive family history of psychosis were associated with early onset of psychosis.


Early development of interictal psychosis in people with epilepsy may reflect other individual vulnerabilities to psychosis rather than epilepsy-related damage.

  I Helfrich , I Scheffrahn , S Bartling , J Weis , V von Felbert , M Middleton , M Kato , S Ergun and D. Schadendorf

Angiogenesis is not only dependent on endothelial cell invasion and proliferation, it also requires pericyte coverage of vascular sprouts for stabilization of vascular walls. Clinical efficacy of angiogenesis inhibitors targeting the vascular endothelial growth factor (VEGF) signaling pathway is still limited to date. We hypothesized that the level of vessel maturation is critically involved in the response to antiangiogenic therapies. To test this hypothesis, we evaluated the vascular network in spontaneously developing melanomas of MT/ret transgenic mice after using PTK787/ZK222584 for anti-VEGF therapy but also analyzed human melanoma metastases taken at clinical relapse in patients undergoing adjuvant treatment using bevacizumab. Both experimental settings showed that tumor vessels, which are resistant to anti-VEGF therapy, are characterized by enhanced vessel diameter and normalization of the vascular bed by coverage of mature pericytes and immunoreactivity for desmin, NG-2, platelet-derived growth factor receptor β, and the late-stage maturity marker smooth muscle actin. Our findings emphasize that the level of mural cell differentiation and stabilization of the vascular wall significantly contribute to the response toward antiangiogenic therapy in melanoma. This study may be useful in paving the way toward a more rational development of second generation antiangiogenic combination therapies and in providing, for the first time, a murine model to study this.

Copyright   |   Desclaimer   |    Privacy Policy   |   Browsers   |   Accessibility