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Biomedical subjects

Hiroshi Mabuchi

Publications and source records attributed to Hiroshi Mabuchi.

At least 55 records · Page 3Linked to original sources
PubMed2005

Risk of colorectal neoplasm in patients with acromegaly and its relationship with serum growth hormone levels.

OBJECTIVES: Acromegalics have been reported to be at an increased risk of colorectal neoplasm. However, the magnitude of the risk is still controversial and the mechanism has not been fully investigated. In this study, we attempted to determine the magnitude of the association between acromegaly and colorectal lesions after taking into account age, gender, smoking status, and treatment status. In addition, we assessed the relationship between colorectal lesions and serum growth hormone (GH) levels in acromegalics. METHODS: We conducted a case-control study by using 19 consecutive untreated patients (male:female = 11:8) who were newly diagnosed with acromegaly between 1990 and 2000. All patients underwent colonoscopy and received a histological diagnosis of colorectal lesions. Prevalence of hyperplastic polyp, adenoma, and carcinoma were compared with the prevalence in 76 controls matched for gender, age, and smoking status. Serum GH levels were compared between acromegalic patients with and without each type of colorectal lesion. RESULTS: The prevalence of hyperplastic polyp, adenoma, and carcinoma were significantly higher in the acromegalic patients compared to the controls (p < 0.05, odds ratios; 8.3, 4.2, and 9.8, respectively). In acromegalics, the presence of hyperplastic polyps and carcinomas were significantly associated with higher serum GH levels after adjusting for the other lesions and age (p < 0.05). CONCLUSIONS: After controlling for age, gender, smoking status, and treatment status, acromegaly was associated with significantly higher prevalence of colorectal hyperplastic polyp, adenoma, and carcinoma. High serum GH levels may be associated with the presence of hyperplastic polyp and carcinoma.

Acromegaly↗
PubMed2005

Large-scale cohort study on the relationship between serum lipid concentrations and risk of cerebrovascular disease under low-dose simvastatin in Japanese patients with hypercholesterolemia: sub-analysis of the Japan Lipid Intervention Trial (J-LIT).

BACKGROUND: The Japan Lipid Intervention Trial was a nationwide cohort study of 52,421 hypercholesterolemic patients treated with open-labeled simvastatin for 6 years under standard clinical practices. Cerebrovascular disease (CVD) is one of the leading causes of death in Japan, but the effect of hypercholesterolemia on CVD has not been well established in Japanese patients. This study aimed to determine the relationship between the risk of CVD and serum lipid concentrations during treatment in Japan. METHODS AND RESULTS: Patients were treated with 5-10 mg/day of simvastatin and all, including those who discontinued simvastatin for any reason, had their lipid concentrations and incidence of CVD monitored for 6 years. Data of 41,088 patients were analyzed in this study, excluding those who had a history of coronary heart disease or CVD. The risk of cerebral infarction was higher in patients whose mean total cholesterol concentrations during treatment were > or = 240 mg/dl, low-density lipoprotein cholesterol concentrations > or = 160 mg/dl, triglycerides > or = 150 mg/dl and high-density lipoprotein cholesterol concentrations <40 mg/dl. There was no obvious correlation between cerebral hemorrhage and serum lipid concentrations. CONCLUSION: Improvement of serum lipid concentrations is important for reducing the incidence of cerebral infarction.

Cerebral Infarction↗
PubMed2005

Gene mutations in adult Japanese patients with dilated cardiomyopathy.

BACKGROUND: Some patients with dilated cardiomyopathy (DCM) have mutations of the genes that encode sarcomeric or cytoskeletal proteins of cardiomyocytes, but the prevalence of these mutations in Japan remains unclear. METHODS AND RESULTS: A group of 99 unrelated adult patients with DCM (familial n=27, sporadic n=72) were screened for the following genes: cardiac beta-myosin heavy chain, cardiac myosin-binding protein C (MYBPC3), regulatory and essential myosin light chains, alpha cardiac actin, alpha tropomyosin, cardiac troponin T, cardiac troponin I, cardiac troponin C, dystrophin, and lamin A/C. A mutation (R820Q) in MYBPC3 was found in an aged patient. In addition, dystrophin mutations were identified in 3 male patients (2 with exon 45-48 deletion and 1 with exon 48-52 deletion). The prevalence of dystrophin mutations in male patients with DCM was 4.4% (3 of 68). No mutations involving amino acid changes were identified in the other genes. CONCLUSIONS: Although cases of adult patients with DCM caused by mutations of the genes encoding sarcomeric or cytoskeletal proteins of cardiomyocytes are infrequent in Japan, it may be advisable to screen older DCM patients for MYBPC3 mutations, and male patients with familial DCM for dystrophin mutations.

Aged↗
PubMed2005

Efficacy of colestimide coadministered with atorvastatin in japanese patients with heterozygous familial hypercholesterolemia (FH).

BACKGROUND: Colestimide, a 2-methylimidazole-epichlorohydrin polymer, is a new bile-acid-sequestering resin, that is 4-fold as powerful at lowering low-density lipoprotein cholesterol (LDL-C) as the conventional resin (cholestyramine). Moreover, colestimide has excellent patient compliance because it is available in tablet form. METHODS AND RESULTS: The clinical efficacy of colestimide coadministered with atorvastatin on lipid and apolipoprotein concentrations was examined in 15 patients (M/F=10/5, mean+/-SE age=54+/-9 years) with heterozygous familial hypercholesterolemia (FH). After a period of wash-out of any lipid-lowering drugs, atorvastatin (20-40 mg) was administered to patients for at least 8 weeks, and then 3 g of colestimide was administered for a further 8 weeks. Total and LDL-C significantly (<0.0001) decreased by 35% from 361 to 233 mg/dl and 41% from 274 to 161 mg/dl, respectively. Addition of colestimide caused a further significant 12% and 20% reduction, respectively, from the initial values to 205 and 129 mg/dl, respectively. Colestimide was also effective in reducing serum LDL-C concentrations in heterozygous FH patients with hypertriglyceridemia (triglycerides>or=150 mg/dl). CONCLUSIONS: When monotherapy with atorvastatin is insufficient to treat severely hypercholesterolemic patients, such as those with heterozygous FH, colestimide acts to reinforce the action of statins.

Anion Exchange Resins↗
PubMed2005

Type III hyperlipoproteinemia exaggerated by Sheehan's syndrome with advanced systemic atherosclerosis: a 28-year clinical course.

A 38-year-old Japanese woman was admitted to hospital for further examination of systemic xanthomas. She had a past history of genital bleeding during her third delivery at the age of 21 years. She was diagnosed with Sheehan's syndrome. Her serum total cholesterol and triglyceride concentrations were 500 and 898 mg/dl, respectively. She was also diagnosed as having type III hyperlipoproteinemia on the basis of the presence of a broad-beta-band on agarose gel electrophoresis and extremely high concentrations of very-low-density lipoprotein cholesterol (310 mg/dl). The diagnosis was later confirmed by her apolipoprotein E isoforms (E2/E2) and genotypes (epsilon2/epsilon2). Thyroid and corticosteroid hormone replacement therapy cured the xanthomas, but also elevated her blood pressure. The serum concentration of intermediate-density lipoprotein cholesterol was consistently high, whereas that of low-density lipoprotein cholesterol was relatively low during the follow-up. Coronary atherosclerosis had already developed by the age of 38 years, and progressed significantly over the following 28 years. Severe stenotic lesions were observed in the bilateral renal arteries and carotid arteries, and in the abdominal aorta when she was 66 years old. These findings suggest that the continuous elevation of intermediate-density lipoprotein cholesterol for a long period contributed to the development of the atherosclerotic lesions.

Adult↗
PubMed2005

Differentiation between patients with takotsubo cardiomyopathy and those with anterior acute myocardial infarction.

BACKGROUND: There has not been a comparison of the electrocardiographic (ECG) finding of ST-segment elevation in the precordial leads in patients with takotsubo cardiomyopathy (TC) and those with anterior acute myocardial infarction (AMI), with regard to the location of the culprit lesion. METHODS AND RESULTS: The present study evaluated 18 patients with TC, and 85 with anterior AMI who were divided into 3 groups: group A had the culprit lesion proximal to both the first septal branch (S1) and the first diagonal branch (D1), group B had the culprit lesion proximal to either S1 or D1, and group C had the culprit lesion distal to both S1 and D1. In patients with TC, reciprocal ST-segment depression in the inferior leads was observed less frequently than in patients in groups A (p<0.0001) and B (p=0.0002), and abnormal Q waves and ST-segment elevation in the inferior leads were observed more frequently than in group A (p=0.0007, p=0.0057, respectively). The ECG findings in TC did not differ from those in group C. CONCLUSION: Electrocardiographic findings may differentiate TC from AMI with a proximal lesion of left anterior descending coronary artery, but not those with distal lesions.

Aged↗
PubMed2005

The risk of cardiovascular events in Japanese hypertensive patients with hypercholesterolemia: sub-analysis of the Japan Lipid Intervention Trial (J-LIT) Study, a large-scale observational cohort study.

Coronary events and stroke are leading causes of death in Japan. However, the effects of hypertension on the risk of coronary events and stroke have not been well established in Japanese hypercholesterolemic patients. This study aimed to determine the relationship between the risk of coronary events or stroke and blood pressure and cholesterol levels during low-dose simvastatin treatment using data from the Japan Lipid Intervention Trial (J-LIT) study (a large scale nationwide cohort study). In the present study, 47,294 hypercholesterolemic patients were treated with open-labeled simvastatin (5 to 10 mg/day) for 6 years by a large number of physicians in a clinical setting. The adjusted incidence rates of coronary events in males and females were 8.9 and 2.3 and those of stroke were 17.6 and 11.3/1000 patients during the 6-year period, respectively. The incidence rate of stroke was higher than that of coronary events in both males and females. An obvious sex difference was observed in terms of the incidence of coronary events. The risk of coronary events, stroke, and total cardiovascular events were increased, with elevations in blood pressure observed in patients treated for hypercholesterolemia. The risk of total cardiovascular events in the groups exhibiting less lipid control increased, with lower blood pressure levels than those of the well-controlled group. For patients with hypercholesterolemia and hypertension, blood pressure should be strictly controlled in order to prevent both coronary events and stroke, and the serum total cholesterol levels should be maintained at low levels as well.

Adult↗
PubMed2005

Reduction of serum ubiquinol-10 and ubiquinone-10 levels by atorvastatin in hypercholesterolemic patients.

Reduction of serum cholesterol levels with statin therapy decreases the risk of coronary heart disease. Inhibition of HMG-CoA reductase by statin results in decreased synthesis of cholesterol and other products downstream of mevalonate, which may produce adverse effects in statin therapy. We studied the reductions of serum ubiquinol-10 and ubiquinone-10 levels in hypercholesterolemic patients treated with atorvastatin. Fourteen patients were treated with 10 mg/day of atorvastatin, and serum lipid, ubiquinol-10 and ubiquinone-10 levels were measured before and after 8 weeks of treatment. Serum total cholesterol and LDL-cholesterol levels decreased significantly. All patients showed definite reductions of serum ubiquinol-10 and ubiquinone-10 levels, and mean levels of serum ubiquinol-10 and ubiquinone-10 levels decreased significantly from 0.81 +/- 0.21 to 0.46 +/- 0.10 microg/ml (p < 0.0001), and from 0.10 +/- 0.06 to 0.06 +/- 0.02 microg/ml (p = 0.0008), respectively. Percent reductions of ubiquinol-10 and those of total cholesterol showed a positive correlation (r = 0.627, p = 0.0165). As atorvastatin reduces serum ubiquinol-10 as well as serum cholesterol levels in all patients, it is imperative that physicians are forewarned about the risks associated with ubiquinol-10 depletion.

Aged↗
PubMed2005

Polymorphisms in four genes related to triglyceride and HDL-cholesterol levels in the general Japanese population in 2000.

We studied the association of six common polymorphisms of four genes related to lipid metabolism with serum lipid levels. We selected single-nucleotide polymorphisms (SNPs) in the genes for cholesteryl ester transfer protein (CETP), lipoprotein lipase (LPL), hepatic lipase (LIPC), and apolipoprotein CIII (APOC3), and studied 2267 individuals randomly selected from the participants of Serum Lipid Survey 2000. There was a significant association of CETP polymorphism (D442G, Int14 +1 G --> A, and TaqIB), LPL polymorphism (S447X), and LIPC polymorphism (-514 --> CT) with HDL-cholesterol levels. We also found a significant association of LPL polymorphism (S447X) and APOC3 polymorphism (SstI) with triglyceride levels. This is the largest database showing the association of common genetic variants in lipid metabolism with serum lipid levels in the general Japanese population. Further study is necessary to elucidate the role of these gene polymorphisms in cardiovascular events.

Apolipoprotein C-III↗
PubMed2005

Cutoff point separating affected and unaffected familial hypercholesterolemic patients validated by LDL-receptor gene mutants.

Familial hypercholesterolemia (FH) results from low-density lipoprotein (LDL) receptor gene mutations. Heterozygotes have twice normal LDL-cholesterol concentrations in early childhood, and experience early myocardial infarction. We demonstrated bimodal cholesterol frequency distributions, independently confirming existence of an identifiable hypercholesterolemic subpopulation. We assayed blood lipids in 181 FH patients genetically diagnosed and 100 unaffected relatives. Receiver operating characteristics curves were constructed. Total cholesterol and LDL-cholesterol concentrations showed bimodality. A total cholesterol cutoff of 225 mg/dl produced results agreeing with DNA testing (specificity, 98.5%; sensitivity, 99.4%). An LDL-cholesterol cutoff of 161-163 mg/dl produced 98.5% specificity and 98.3% sensitivity. Areas under curves were 0.9826 +/- 0.0058 for total cholesterol, and 0.9852 +/- 0.0043 for LDL-cholesterol. In conclusion, we define total cholesterol and LDL-cholesterol levels of 225 and 160 mg/dl, respectively, as cutoff points of normal subjects and FH patients.

Heterozygote↗
PubMed2005

Risk evaluation of coronary heart disease and cerebrovascular disease by the Japan Atherosclerosis Society Guidelines 2002 using the cohort of the Holicos-PAT study.

Our purpose in this study was to evaluate the new JAS guidelines as a risk assessment tool in Japanese patients with hypercholesterolemia, using the cohort of the Holicos-PAT study. The Holicos-PAT study was designed as a prospective observational study. 2039 patients were followed with or without pravastatin for 5 years. We assessed coronary heart disease (CHD) and cerebrovascular disease (CVD) risks by the patient categories described in the JAS guidelines. In the Holicos-PAT study, the primary endpoints were CHD, and the secondary endpoints were CVD and total mortality. CHD event includes onset and worsening of angina pectoris, performing CABG or PTCA, non-fatal and fatal myocardial infarction, and death from CHD including heart death and sudden death. CVD events are onset or recurrence of cerebral infarction, onset of cerebral hemorrhage, and death from cerebral infarction or hemorrhage. The event rates were calculated by the person-years method, and the differences in event rates between category groups were analyzed by chi-square test. The event rates of CHD in Category A, B1, B2, B3, B4 and C, were 1.1, 4.0, 2.8, 5.7, 18.2 and 38.8 per 1,000 person-years. The rates of CHD events in the higher risk category groups, Category B4 group (p = 0.004 in whole patients) and C group (p < 0.001 in whole patients), were significantly higher than that in the combined category groups A + B1 + B2. The event rates of CVD in Category A, B1, B2, B3, B4 and C, were 2.1, 1.8, 1.8, 0.6, 10.8 and 6.4 per 1,000 person-years. The event rates of CHD in men were significantly higher than those in women, in categories B4 (p < 0.001) and C (p < 0.001). From these results, each category classified by accumulation of risk factors, showed increasing event rates of CHD and CVD. The categories in the JAS guidelines are useful to assess CHD and CVD risk in Japanese patients with hypercholesterolemia. However, the risk evaluation by the JAS guideline categories may underestimate the risk in men and overestimate it in women.

Cerebrovascular Disorders↗
PubMed2005

Serum lipid survey and its recent trend in the general Japanese population in 2000.

To determine the recent serum lipid levels and other serum variables in the general Japanese population and trends in their changes over the past 40 years, a nationwide survey of serum lipid levels was conducted in 36 institutes from various districts around Japan in 2000. The total number of subjects was 12,839, aged 4 through 99 years. The mean total cholesterol level was 201 mg/dl; 202 mg/dl in men and 200 mg/dl in women. The mean HDL-cholesterol level was 59 mg/dl; 55 mg/dl in men and 65 mg/dl in women. The mean LDL-cholesterol level was 118 mg/dl; 121 mg/dl in men and 115 mg/dl in women. The mean triglyceride level was 118 mg/dl; 136 mg/dl in men and 92 mg/dl in women. The total cholesterol level slightly increased by 5 mg/dl in 10 years. Although the triglyceride level in women did not change, the triglyceride level in men increased over 10 years, especially in the 30s through 70s age bracket, indicating a possible increase in metabolic syndromes in the future. The present results will become the standard serum lipid level data for the Japanese people, and succeeding 10-year surveys will clarify the trends of lipid levels in this country.

Adolescent↗
PubMed2005

Two novel mutations, L490R and V561X, of the transferrin receptor 2 gene in Japanese patients with hemochromatosis.

BACKGROUND AND OBJECTIVES: The low prevalence of the C282Y mutation of the HFE gene in Japan means that the genetic background of hemochromatosis in Japanese patients remains unclear. In a previous report, we showed that 3 patients from one family had an AVAQ 594-597 deletion of the transferrin receptor (TfR2) gene. This suggests that the TfR2 gene is involved in hemochromatosis in Japanese patients. DESIGN AND METHODS: Nine patients clinically diagnosed with hemochromatosis were included in the study. DNA was extracted from whole blood samples collected with informed consent. The HFE and TfR2 genes were analyzed by sequencing the coding region and splicing sites. RESULTS: There were no mutations in the HFE gene. In the TfR2 gene, 2 novel mutations, 1469T->G (L490R) and 1665delC (V561X), were found in 2 patients. A known variation, 714C-> (I238M), was also found in the patient with L490R. The patient homozygous for both L490R and I238M presented with a mild manifestation of hemochromatosis at the age of 41 years. His liver was cirrhotic with parenchymal iron deposits and the result of a glucose tolerance test was compatible with diabetes mellitus. The patient homozygous for V561X had severe iron overload with the triad of cirrhosis, diabetes mellitus and skin pigmentation at the age of 58 years. INTERPRETATION AND CONCLUSIONS: Taken together with the previous report, 5 of our 12 patients with hemochromatosis manifesting in middle age had mutations in the TfR2 gene. Thus, TfR2 plays a role in the pathogenesis of hemochromatosis in Japan.

Adult↗
PubMed2005

The first reported case of spotted fever in Fukui Prefecture, the northern part of central Japan.

A 53-year-old man visited Mt. Arashima-dake in Fukui Prefecture, and was infested by a tick-like organism. He visited a local clinic on July 12, 2004, complaining of high fever, general fatigue and rash. After several days without definite diagnosis, he was admitted to the Fukui Prefectural Hospital, where he was treated with minocycline hydrochloride for 10 days until recovery. His clinical symptoms on admission were high fever (39.6 degrees C), erythematous eruption, eschar on the right upper arm, and regional lymphoadenopathy. The epidemiological status and some clinical findings strongly suggested spotted fever (SF), and SF was confirmed based on the finding that his sera were reactive only to antigens of the SF group rickettsiae in the indirect immunoperoxidase analysis. This case is the first official report of SF rickettsiosis in Fukui Prefecture, the northern part of central Japan.

Anti-Bacterial Agents↗
PubMed2004

Two novel mutations of PTEN gene in Japanese patients with Cowden syndrome.

Cowden syndrome (CS), also known as multiple hamartoma syndrome, is an autosomal dominant cancer syndrome associated with high risk of breast and thyroid cancer. In three unrelated Japanese CS patients, three PTEN germline mutations were identified, including two novel ones: 589A --> T, resulting in Lys197Stop, and 219-222delAAGA. We also detected a previously reported mutation: 697C --> T, resulting in Arg233Stop. Reports from Western countries have indicated that approximately two-thirds of mutations are found in exons 5, 7, and 8, which is almost the same frequency as found in Japanese CS. No genotype-phenotype correlations have been found in CS patients from 21 Japanese families.

Adult↗
PubMed2004

Detailed analysis of serum lipids and lipoproteins from Japanese type III hyperlipoproteinemia with apolipoprotein E2/2 phenotype.

BACKGROUND: To clarify a detailed profile of serum lipids, lipoproteins and apolipoproteins (apo) in type III hyperlipoproteinemia (HLP) with apolipoprotein E (apo E) phenotype 2/2. METHODS: Nineteen consecutive Japanese type III HLP (9 men, 10 women) were studied. All had hypertriglyceridemia and 74% showed hypercholesterolemia. RESULTS: The degree of hyperlipidemia [total cholesterol (TC) 8.1 +/- 3.2 mmol/l, triglycerides (TG) 5.2 +/- 2.9 mmol/l] was milder than that in type III HLP in western countries. Lipoprotein fractions analyzed by ultracentrifugation showed that very low density lipoprotein cholesterol (VLDL-C) concentrations were considerably increased and that intermediate density lipoprotein cholesterol (IDL-C) concentrations were also increased, whereas low-density lipoprotein cholesterol (LDL-C) concentrations were low. Serum apo A-I, A-II and B concentrations were not increased, while apo C-II, C-III and E concentrations were considerably increased. However, the increase of apo E concentrations in the study subjects was far more pronounced than that of apo C-III, causing the ratio of apo E/C-III to be considerably higher than hyperlipidemia with other apo E phenotypes. CONCLUSION: By using this index apo E/C-III, it is possible to segregate type III HLP with apo E2/2 phenotype from other types of hyperlipidemia.

Apolipoprotein E2↗