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Articles by S Goto
Total Records ( 8 ) for S Goto
  R Roussel , F Travert , B Pasquet , P. W. F Wilson , S. C Smith , S Goto , P Ravaud , M Marre , A Porath , D. L Bhatt , P. G Steg and for the Reduction of Atherothrombosis for Continued Health (REACH) Registry Investigators
 

Background  Metformin is recommended in type 2 diabetes mellitus because it reduced mortality among overweight participants in the United Kingdom Prospective Diabetes Study when used mainly as a means of primary prevention. However, metformin is often not considered in patients with cardiovascular conditions because of concerns about its safety.

Methods  We assessed whether metformin use was associated with a difference in mortality among patients with atherothrombosis. The study sample comprised 19 691 patients having diabetes with established atherothrombosis participating in the Reduction of Atherothrombosis for Continued Health (REACH) Registry between December 1, 2003, and December 31, 2004, treated with or without metformin. Multivariable adjustment and propensity score were used to account for baseline differences. The main outcome measure was 2-year mortality.

Results  The mortality rates were 6.3% (95% confidence interval [CI], 5.2%-7.4%) with metformin and 9.8% 8.4%-11.2%) without metformin; the adjusted hazard ratio (HR) was 0.76 (0.65-0.89; P < .001). Association with lower mortality was consistent among subgroups, noticeably in patients with a history of congestive heart failure (HR, 0.69; 95% CI, 0.54-0.90; P = .006), patients older than 65 years (0.77; 0.62-0.95; P = .02), and patients with an estimated creatinine clearance of 30 to 60 mL/min/1.73 m2 (0.64; 95% CI, 0.48-0.86; P = .003) (to convert creatinine clearance to mL/s/m2, multiply by 0.0167).

Conclusions  Metformin use may decrease mortality among patients with diabetes when used as a means of secondary prevention, including subsets of patients in whom metformin use is not now recommended. Metformin use should be tested prospectively in this population to confirm its effect on survival.

  Y Yamanishi , M Hattori , M Kotera , S Goto and M. Kanehisa
 

Motivation: The IUBMB's Enzyme Nomenclature system, commonly known as the Enzyme Commission (EC) numbers, plays key roles in classifying enzymatic reactions and in linking the enzyme genes or proteins to reactions in metabolic pathways. There are numerous reactions known to be present in various pathways but without any official EC numbers, most of which have no hope to be given ones because of the lack of the published articles on enzyme assays.

Results: In this article we propose a new method to predict the potential EC numbers to given reactant pairs (substrates and products) or uncharacterized reactions, and a web-server named E-zyme as an application. This technology is based on our original biochemical transformation pattern which we call an ‘RDM pattern’, and consists of three steps: (i) graph alignment of a query reactant pair (substrates and products) for computing the query RDM pattern, (ii) multi-layered partial template matching by comparing the query RDM pattern with template patterns related with known EC numbers and (iii) weighted major voting scheme for selecting appropriate EC numbers. As the result, cross-validation experiments show that the proposed method achieves both high coverage and high prediction accuracy at a practical level, and consistently outperforms the previous method.

Availability: The E-zyme system is available at http://www.genome.jp/tools/e-zyme/

Contact: kanehisa@kuicr.kyoto-u.ac.jp

  L Folkersen , D Diez , C. E Wheelock , J. Z Haeggstrom , S Goto , P Eriksson and A. Gabrielsen
 

Summary: Whole-genome microarrays allow us to interrogate the entire transcriptome of a cell. Affymetrix microarrays are constructed using several probes that match to different regions of a gene and a summarization step reduces this complexity into a single value, representing the expression level of the gene or the expression level of an exon in the case of exon arrays. However, this simplification eliminates information that might be useful when focusing on specific genes of interest. To address these limitations, we present a software package for the R platform that allows detailed analysis of expression at the probe level. The package matches the probe sequences against a target gene sequence (either mRNA or DNA) and shows the expression levels of each probe along the gene. It also features functions to fit a linear regression based on several genetic models that enables study of the relationship between gene expression and genotype.

  S Goto , H Fujii , Y Matsui and M. Fukagawa
 

A 59-year-old female who was on dialysis due to diabetic nephropathy was referred to our hospital for severe hyperparathyroidism refractory to intravenous vitamin D receptor activator treatment. With subsequent cinacalcet hydrochloride treatment, parathyroid hormone (PTH) levels were only slightly suppressed. However, progressive increases were observed in serum alkaline phosphatase (ALP) and bone-specific alkaline phosphatase (BAP) levels with mild hypocalcaemia. A bone biopsy, obtained immediately before surgical parathyroidectomy after 3 months of cinacalcet treatment, revealed no disappearance of osteoclasts. These data suggest that cinacalcet hydrochloride treatment may induce a marked promotion of bone formation by mechanisms distinct from hungry bone syndrome that usually develops after parathyroidectomy.

  S Goto , M Yamadori , N Igaki , J. I Kim and M. Fukagawa
 

Ascites, oliguria and increasing serum creatinine levels are often noted in patients with acute kidney injury. However, these presentations are also observed in patients with intraperitoneal urinary leakage. Bladder perforation without obvious trauma is sometimes mistaken for acute kidney injury. We report two cases of bladder perforation resembling acute kidney injury. The first case was a 37-year-old woman with delayed intraperitoneal urinary leakage following total abdominal hysterectomy, and the second was a 70-year-old woman with spontaneous bladder perforation. Although the initial diagnosis in both cases was acute kidney injury, rupture of the urinary bladder was later identified.

  H Fujii , F Nishijima , S Goto , M Sugano , H Yamato , R Kitazawa , S Kitazawa and M. Fukagawa
 

Background. Chronic kidney disease (CKD) is an important risk factor for cardiovascular disease (CVD). Increased oxidative stress plays a role in the pathogenesis of CVD in CKD patients. The oral charcoal adsorbent AST-120 attenuates the progression of CKD possibly by removing uraemic toxins such as indoxyl sulfate (IS), and reduces oxidative stress. We investigated the relationship between oxidative stress and cardiac damage in CKD and its prevention by AST-120.

Methods. Male Lewis rats were administered adriamycin at 8 weeks of age, and the right kidney was removed at 12 weeks of age. From 14 weeks of age, the rats were treated daily with AST-120 (n = 8) or were untreated (control group, n = 8). At 34 weeks of age, the rats were killed and urinary and blood biochemical tests as well as cardiac histological analyses were performed.

Results. At 14 weeks of age, there were no significant differences in blood pressure, renal function (creatinine clearance: 1.54 ± 0.28 mL/min versus 1.60 ± 0.22 mL/min), oxidative stress markers or other biochemical data between the control and AST-120 groups. At 34 weeks, despite similar blood pressure and renal function (creatinine clearance: 0.78 ± 0.46 mL/min versus 0.75 ± 0.54 mL/min), serum concentrations of IS and urinary excretion of 8-hydroxydeoxyguanosine (8-OHdG), acrolein and IS were significantly lower in the AST-120 group than in the control group. Heart volume, left ventricular volume and cardiac fibrosis were significantly smaller in the experimental AST-120 group than in the control group. Immunohistological analysis revealed that the numbers of 8-OHdG- and acrolein-positive cardiomyocytes and the degrees of myocardial and perivascular fibrosis were ameliorated by AST-120 administration. The myocardial fibrosis score was significantly associated with the 8-OHdG- (r = 0.848, P < 0.001) and acrolein-positive (r = 0.812, P < 0.001) cell scores. The perivascular fibrosis score was also significantly associated with the 8-OHdG- (r = 0.906, P < 0.0001) and acrolein-positive (r = 0.789, P < 0.001) cell scores.

Conclusions. Oxidative stress is suggested to play a key role in the development of cardiac hypertrophy and fibrosis in CKD. AST-120 may suppress oxidative stress and reduce cardiac damage in CKD.

 
 
 
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