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Yoshio Goto

Publications and source records attributed to Yoshio Goto.

6 recordsLinked to original sources
PubMed2006

Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial.

BACKGROUND: Evidence-based treatment for hypercholesterolaemia in Japan has been hindered by the lack of direct evidence in this population. Our aim was to assess whether evidence for treatment with statins derived from western populations can be extrapolated to the Japanese population. METHODS: In this prospective, randomised, open-labelled, blinded study, patients with hypercholesterolaemia (total cholesterol 5.69-6.98 mmol/L) and no history of coronary heart disease or stroke were randomly assigned diet or diet plus 10-20 mg pravastatin daily. The primary endpoint was the first occurrence of coronary heart disease. Statistical analyses were done by intention to treat. This trial is registered at ClinicalTrials.gov, number NCT00211705. FINDINGS: 3966 patients were randomly assigned to the diet group and 3866 to the diet plus pravastatin group. Mean follow-up was 5.3 years. At the end of study, 471 and 522 patients had withdrawn, died, or been lost to follow-up in the diet and diet plus pravastatin groups, respectively. Mean total cholesterol was reduced by 2.1% (from 6.27 mmol/L to 6.13 mmol/L) and 11.5% (from 6.27 mmol/L to 5.55 mmol/L) and mean LDL cholesterol by 3.2% (from 4.05 mmol/L to 3.90 mmol/L) and 18.0% (from 4.05 mmol/L to 3.31 mmol/L) in the diet and the diet plus pravastatin groups, respectively. Coronary heart disease was significantly lower in the diet plus pravastatin group than in the diet alone group (66 events vs 101 events; HR 0.67, 95% CI 0.49-0.91; p=0.01). There was no difference in the incidence of malignant neoplasms or other serious adverse events between the two groups. INTERPRETATION: Treatment with a low dose of pravastatin reduces the risk of coronary heart disease in Japan by much the same amount as higher doses have shown in Europe and the USA.

Adult↗
PubMed2006

[JATOS].

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Aged↗
PubMed2002

Binding of dioxygen to non-metal sites in proteins: exploration of the importance of binding site size versus hydrophobicity in the copper amine oxidase from Hansenula polymorpha.

Copper amine oxidases (CAOs) contain 2,4,5-trihydroxyphenylalanyl quinone (TPQ) and a copper ion in their active sites, catalyzing amine oxidation to aldehyde and ammonia concomitant with the reduction of molecular oxygen to hydrogen peroxide. Kinetic studies on the CAO from bovine serum (BSAO) [Su and Klinman (1999) Biochemistry 37, 12513-12525] and the recent reports on the cobalt substituted form of the enzyme from Hansenula polymorpha (HPAO) [Mills and Klinman (2000) J. Am. Chem. Soc. 122, 9897-9904, and Mills et al. (2002) Biochemistry, 41, 10577-10584] support pre-binding of molecular oxygen prior to a rate-limiting electron transfer from the reduced form of TPQ (p-aminohydroquinone form) to dioxygen. Although there is significant sequence homology between BSAO and HPAO, k(cat)/K(m)(O2) for BSAO under the optimal condition is one order of magnitude lower than that for HPAO. From a comparison of amino acid sequences for BSAO and HPAO, together with the X-ray crystal structure of HPAO, a plausible dioxygen pre-binding site has been identified that involves Y407, L425, and M634 in HPAO; the latter two residues are altered in BSAO to A490 and T695. To determine which of these residues plays a greater role in dioxygen chemistry, k(cat)/K(m)(O2) was determined in HPAO for the M634 --> T and L425 --> A mutants. The L425 --> A mutation does not alter k(cat)/K(m)(O2) to a large extent, whereas the M634 --> T decreased k(cat)/K(m)(O2) by one order of a magnitude, creating a catalyst that is similar to BSAO. A series of mutants at M634 (to F, L, and Q) were, therefore, prepared in HPAO and characterized with regard to k(cat)/K(m)(O2) as a function of pH. Structure reactivity correlations show a linear relationship of rate with side chain volume, rather than hydrophobicity, indicating that dioxygen reactivity increases with the bulk of the residue at position 634. This site also shows specificity for O2, in relation to the co-gas N2, since substitution of the inert gas N2 by either Ar or He has no effect on measured rates. In particular, He gas is expected to have little affinity for protein at 1 atmospheric pressure, implying little or no binding by N2 as well.

Amine Oxidase (Copper-Containing)↗
PubMed2002

Mechanistic comparison of the cobalt-substituted and wild-type copper amine oxidase from Hansenula polymorpha.

A recent report by Mills and Klinman [Mills, S. A., and Klinman, J. P. (2000) J. Am. Chem. Soc. 122, 9897-9904] described the preparation and initial characterization of a cobalt-substituted form of the copper amine oxidase from Hansenula polymorpha (HPAO). This enzyme was found to be fully catalytically active at saturating substrate concentrations, but with a K(m) for O(2) approximately 70-fold higher than that of the copper-containing, wild-type enzyme. Herein, we report a detailed analysis of the mechanism of catalysis for the wild-type and the cobalt-substituted forms of HPAO. Both forms of enzyme are concluded to utilize the same mechanism for oxygen reduction, involving initial, rate-limiting electron transfer from the reduced cofactor of the enzyme to prebound dioxygen. Superoxide formed in this manner is stabilized by the active site metal, facilitating the transfer of a second electron and two protons to form the product hydrogen peroxide. The elevated K(m) for O(2) at the dioxygen binding site in Co-substituted HPAO, relative to that of wild-type HPAO, is proposed to be due to a change in the net charge at the adjacent metal site from +1 (cupric hydroxide) in wild-type enzyme to +2 (cobaltous H(2)O) in cobalt-substituted HPAO.

Amine Oxidase (Copper-Containing)↗