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Biomedical subjects

H Toshima

Publications and source records attributed to H Toshima.

At least 37 records · Page 2Linked to original sources
PubMed1996

Xanthine oxidase mediates cyclic flow variations in a canine model of coronary arterial thrombosis.

We investigated the hypothesis that xanthine oxidase (XO) mediates platelet aggregation and cyclic flow variations (CFVs) in stenosed canine coronary arteries. CFVs were produced by an external constrictor placed at the site of the coronary artery with the injured endothelium. The severity of CFVs was evaluated by a pulsed Doppler flow probe. If CFVs developed, dogs intravenously received allopurinol, a specific XO inhibitor. The transcardiac gradient (difference between coronary vein and left atrium) of purine metabolites was determined during CFVs and after allopurinol administration. Allopurinol significantly reduced CFVs (from 8 +/- 1 to 1 +/- 1 cycles/h, P < 0.01, n = 14), whereas saline did not (from 8 +/- 1 to 7 +/- 1 cycles/h, n = 7). In seven dogs with CFVs, the transcardiac gradient of xanthine and uric acid concentrations significantly increased after the establishment of CFVs and significantly decreased after the administration of allopurinol. In vitro platelet studies showed that XO enhanced (from 30.9 +/- 2.0 to 47.6 +/- 1.5%, P < 0.0001, n = 10) and allopurinol inhibited ADP-induced platelet aggregation (from 48.3 +/- 1.3 to 24.8 +/- 1.5%, P < 0.0001, n = 10). Our results indicate that allopurinol inhibits platelet aggregation in vitro and provides a protection against CFVs in vivo. Thus XO may be an important mediator in this model.

Allopurinol↗
PubMed1996

Chronic L-arginine administration attenuates cardiac hypertrophy in spontaneously hypertensive rats.

Nitric oxide inhibits proliferation and migration of vascular smooth muscle cells and contractility of cardiomyocytes in vitro. In spontaneously hypertensive rats (SHR), evidence suggests intrinsic abnormalities of the L-arginine-nitric oxide axis, such as low cGMP-dependent protein kinase in the heart and abnormal L-arginine metabolism. To investigate the in vivo effect of L-arginine on cardiac hypertrophy, 30 SHR and 30 Wistar-Kyoto rats (WKY) were randomly grouped to receive L-arginine (7.5 g/L in drinking water) or vehicle for 12 weeks. L-Arginine treatment did not affect body weight or arterial pressure in either strain. In vehicle-treated animals, the heart/body weight ratio was significantly higher in SHR than in WKY (P < .01). L-Arginine treatment decreased the heart/body weight ratio in SHR (P < .05) but did not affect it in WKY. Expression of skeletal alpha-actin mRNA, known to be expressed in the hypertrophied myocardium, was attenuated in L-arginine-treated SHR compared with vehicle-treated SHR. Cardiac cGMP content and nitrate/nitrite content were less in SHR than WKY. L-Arginine treatment increased these levels only in SHR, suggesting enhanced nitric oxide production. Thus, chronic L-arginine administration attenuated cardiac hypertrophy independently of blood pressure and increased myocardial content of cGMP and nitrate/nitrite. Our results suggest that abnormality of the cardiac L-arginine-nitric oxide axis may play an important role in the pathogenesis of cardiac hypertrophy in SHR.

Actins↗
PubMed1996

Twenty-five-year prediction of stroke deaths in the seven countries study: the role of blood pressure and its changes.

BACKGROUND AND PURPOSE: This report explores the prediction of long-term stroke mortality in cohorts of the Seven Countries Study. METHODS: Sixteen cohorts of men aged 40 to 59 years at entry were examined at years 0, 5, and 10, with mortality follow-up through 25 years. RESULTS: Stroke death rates in 25 years were high in rural Serbia, Croatia, and Japan; intermediate in Italy, Greece, and urban Serbia; and low in Finland, the Netherlands, and the United States. Age and blood pressure were powerful predictors of 25-year stroke mortality in almost all cohorts and countries. Proportional hazards regression coefficients were .0232 increase in stroke death hazard per millimeter of mercury (t=14.60) for systolic blood pressure and .0409 (t=13.41) for diastolic blood pressure. Moderate blood pressure increases from low usual levels were associated with lower stroke mortality rates in years 10 to 25. Increases of blood pressure starting from high usual levels were associated with increased rates of stroke mortality. Systolic blood pressure was associated with stroke mortality at given levels of diastolic pressure, but diastolic blood pressure was not predictive of stroke mortality at given levels of systolic blood pressure. CONCLUSIONS: Associations of systolic and diastolic blood pressure with stroke mortality were similar in cultures with different stroke mortality rates. Increases in blood pressure were associated with subsequent excess stroke mortality only in those who started from high usual levels; this study finds lower stroke risk in those men whose blood pressure increased moderately from low usual levels. Diastolic blood pressure is not independently associated with stroke risk in these populations.

Adult↗
PubMed1996

Induction of DNA breaks in cardiac myoblast cells by norepinephrine.

We measured DNA single strand breaks (SSB) in cardiac myoblast cells in response to norepinephrine (NE) stimulation. Rat cardiac myoblast cells (H9c2) were stimulated with concentrations of 100 microMs to 1 mM NE for 2, 3, 4, and 12 hours after prior incubation with control solution, bunazosin, propranolol, verapamil, or captopril for 30 min. The DNA damage was measured by fluorometric alkaline elution. The strand scission factor, an index of the severity of SSB, increased slightly after stimulation with 200 microMs NE for 12 hours and with 1 mM NE for 4 hours. This increase was prevented by catalase or superoxide dismutase, which prevent production or accumulation of active oxygen radicals, during the stimulation, but not by pretreatment with a alpha-receptor antagonist, a beta-adrenergic receptor antagonist, a Ca2+ antagonist, or an angiotensin converting enzyme inhibitor. Thus, DNA SSB were induced by NE in cardiac myoblast cells. Certain active oxygen species may contribute to the DNA damage induced by NE.

Adrenergic alpha-Agonists↗
PubMed1996

Comparison of multivariate predictive power of major risk factors for coronary heart diseases in different countries: results from eight nations of the Seven Countries Study, 25-year follow-up.

BACKGROUND: It was hypothesized that among eight national groups of men aged 40-59 years enrolled in the Seven Countries Study, the multivariate coefficients of major risk factors predicting coronary heart disease mortality over 25 years would be relatively similar. MATERIALS AND METHODS: Sixteen cohorts were located in eight nations and pooled, comprising one cohort in the USA, two in Finland, one in the Netherlands, three in Italy, two in Croatia (former Yugoslavia), three in Serbia (Yugoslavia), two in Greece and two in Japan, for a total of over 12000 subjects at entry. Coronary heart disease (CHD) mortality was defined as fatal myocardial infarction or sudden coronary death, and proportional hazard models were solved, for each country, with age, serum cholesterol level, systolic blood pressure and cigarette consumption as covariates. RESULTS: The relationships between risk factors and CHD mortality were statistically significant for all risk factors and for all countries, except for age in Croatia and Japan, cholesterol in Croatia and Japan, systolic blood pressure in Serbia and Greece, and cigarette-smoking in the Netherlands, Croatia, Serbia and Greece. When comparing all pairs of coefficients (28 comparisons for each factor) significant differences were found on four occasions for age, on six occasions for cholesterol, on no occasion for blood pressure and on four occasions for cigarette-smoking. Other tests suggested a substantial homogeneity among multivariate coefficients. Estimates for pooled coefficients were: age, in years, 0.0570 (95% confidence limits 0.0465 and 0.0673); relative risk for 5 years 1.33 (95% confidence limits 1.26 and 1.40); serum cholesterol level in mg/dl, 0.0057 (95% confidence limits 0.0045 and 0.0069); relative risk for 40 mg/dl 1.31 (95% confidence limits 1.20 and 1.31); systolic blood pressure in mmHg, 0.0160, (95% confidence limits 0.0134 and 0.0185), relative risk for 20 mmHg 1.38 (95% confidence limits 1.31 and 1.45); cigarettes per day, 0.0220 (95% confidence limits 0.0170 and 0.0272); relative risk for 10 cigarettes per day 1.25 (95% confidence limits 1.18 and 1.31). CONCLUSIONS: Great similarities were found in the multivariate coefficients of major coronary risk factors to CHD risk derived from population samples varying in CHD frequency.

Adult↗
PubMed1995

A myosin missense mutation, not a null allele, causes familial hypertrophic cardiomyopathy.

BACKGROUND: Hypertrophic cardiomyopathy (HCM) is characterized by myocardial hypertrophy of unknown etiology. Missense mutations of the cardiac beta-myosin-heavy-chain (beta-MHC) gene that may be responsible for cardiac hypertrophy have been detected in patients with HCM. On the other hand, gross structural abnormalities in the cardiac beta-MHC gene, ie, an alpha/beta hybrid gene and partial deletion of the gene, have also been reported. The direct correlation between gross abnormalities and development of HCM is not well understood. METHODS AND RESULTS: We analyzed the structure of the cardiac beta-MHC gene from patients with HCM by using polymerase chain reaction-DNA conformation polymorphism analysis and found two sequence variations in exons 3 and 22 in one patient. These sequence variations at codon 54 (exon 3; nonsense mutation) and codon 870 (exon 22; Arg-to-His mutation) were identified by direct sequencing and dot-blot hybridization with allele-specific oligonucleotide probes. Relatives of this patient were examined for the mutations. It was revealed that the missense mutation was inherited from the affected father and the nonsense mutation from the unaffected grandmother through the unaffected mother. In addition, the missense mutation was also found in seven other patients from two other unrelated multiplex HCM families. CONCLUSIONS: The Arg870His mutation was suggested to cause HCM. In contrast, the gene with the nonsense mutation would encode for a cardiac beta-MHC protein of only 53 amino acid residues, which may be too short to be incorporated into the thick filament assembly of cardiac myosin chains and showed no dominant phenotype of heart disease. This is the first report of a nonsense mutation in the human cardiac beta-MHC gene.

Base Sequence↗
PubMed1995

Indium-111 antimyosin monoclonal antibody Fab imaging in patients with cardiomyopathy.

Six patients with cardiomyopathy were imaged following intravenous injection of an indium-111 labeled monoclonal antibody directed against the heavy chain of cardiac myosin. Two patients had hypertrophic non-obstructive cardiomyopathy (HNCM), two patients had dilated cardiomyopathy (DCM), and two patients had specific heart muscle disease. One of 2 patients with HNCM and one of 2 patients with DCM had a positive antimyosin scan. The 2 patients with specific heart muscle disease manifested persistent blood pool activity of the antibody, thereby precluding interpretation of the images. The present report demonstrates that antimyosin antibody imaging may provide evidence of myocardial injury, or necrosis in some patients with cardiomyopathy.

Adolescent↗
PubMed1995

Disappearance of giant negative T waves in patients with the Japanese form of apical hypertrophy.

OBJECTIVES: The present study investigated the long-term changes in the electrocardiographic (ECG) hallmarks of the Japanese form of apical hypertrophy. BACKGROUND: Giant negative T waves and tall R waves in the left precordial leads are the ECG hallmarks of the Japanese form of apical hypertrophy. However, the long-term course is largely unknown. METHODS: Twenty-nine patients with apical hypertrophy (26 men, 3 women, mean age +/- SD 50.4 +/- 8.2 years) who showed left precordial giant negative T waves (< or = -10 mm) and tall R waves (> or = 26 mm) and spade configuration in the left ventriculogram were followed up for 10.9 +/- 3.7 years. RESULTS: The intermediate follow-up ECGs (5 to 9 years) showed disappearance of giant negative T waves in 31% and of tall R waves in lead V5 in 6%. At the long-term follow-up study (> or = 10 years), loss of giant negative T waves increased to 71%, with average T wave negativity in lead V4 or V5 decreasing from -16.5 +/- 5.1 to -6.9 +/- 4.2 mm. These T wave changes were associated with decreases in R wave amplitude in lead V5 from 40.7 +/- 9.6 to 26.1 +/- 13.8 mm, with loss of tall R waves in lead V5 in 38% of patients and development of abnormal Q waves in two patients. CONCLUSIONS: During the long-term follow-up of the Japanese form of apical hypertrophy, giant negative T waves disappeared in association with decreases in R wave amplitude in lead V5, indicating that these ECG hallmarks are clinical features that evolve progressively during the natural course of the disease.

Adult↗
PubMed1995

DNA typing of HLA class II genes in Japanese patients with dilated cardiomyopathy.

HLA class II genes (DRB, DQA, DQB, DPA, and DPB) were typed at the DNA level using polymerase chain reaction/sequence-specific oligonucleotide probe analysis in 78 unrelated patients with DCM and 336 unrelated healthy controls to elucidate the HLA alleles or HLA haplotypes associated with DCM. The frequencies of DRB1*1401 (15.4% v 4.5%, RR = 3.90, P < 0.0005, Pc < 0.03), DQB1*0503 (14.1% v 5.4%, RR = 2.93, P < 0.007) and DRB1*1401-DQB1*0503 haplotype (11.5% v 1.5%, RR = 8.24, P < 0.00001, Pc < 0.01) were increased in the DCM patients. The frequency of HLA-DRB1*1101 (9.0% v 3.0%, RR = 3.26, P < 0.02) also was increased in the patients. In addition, the frequencies of DQB1*0604 and DPB1*0401 were increased in the DRB1*1401 and DRB1*1101 negative patients. In contrast, the frequencies of DQB1*0303 (19.2% v 30.7%, RR = 0.55, P < 0.05) and DRB1*0901-DQB1*0303 haplotype (16.7% v 29.8%, RR = 0.49, P < 0.02) were decreased in the DCM group. Disease susceptibility to DCM in the Japanese population, thus, may be controlled in part by a gene (or genes) in close linkage disequilibrium with DRB1*1401-DQB1*0503, DRB1*1101-DQB1*0301, and DQB1*0604-DPB1*0401 haplotypes, while the resistance to DCM may be associated with the DRB1*0901-DQB1*0303 haplotype.

Adolescent↗
PubMed1995

Follow-up of 2,733 Japanese patients with myocardial infarction.

Two thousand, seven hundred and thirty-three patients with acute myocardial infarction (AMI) who were admitted to our 11 institutions between 1983 and 1988, examined by coronary arteriography and discharged alive, were followed for an average of 2.9 years. During the follow-up period, 212 patients (7.6%) died. The factors that governed the prognosis of myocardial infarction after discharge were advanced age, female gender, obesity, previous infarction, angina pectoris more than 1 month before the onset of AMI, post-infarction angina, multiple-vessel diseases, advanced stage by Killip's and/or Forrester's classification on admission, elevated pulmonary capillary arterial pressure, decreased cardiac index, decreased left ventricular ejection fraction, increased left ventricular end-diastolic volume and left ventricular aneurysm before hospital discharge. Patients with ventricular tachycardia or ventricular fibrillation during hospitalization showed a poor prognosis. In contrast, patients who received intracoronary thrombolysis, or emergent and/or elective percutaneous transluminal coronary angioplasty showed a favorable prognosis.

Adult↗
PubMed1995

Factors governing re-infarction in patients with myocardial infarction in Japan.

The subjects consisted of 2,733 patients with acute myocardial infarction (AMI) who were admitted to our 11 institutions between 1983 and 1988, examined by coronary arteriography, and discharged alive. The patients were followed for an average of 2.9 years after discharge. During the follow-up period, re-infarction occurred in 172 patients (6.3%). The factors associated with re-infarction were total cholesterol of more than 250 mg/dl, HDL-cholesterol of less than 35 mg/dl and diabetes mellitus. The rate of re-infarction was also high in patients who had had a previous infarction before admission, angina pectoris before or after the onset of AMI or multiple-vessel disease. In contrast, intracoronary thrombolysis reduced the rate of re-infarction.

Angina Pectoris↗
PubMed1995

The seven countries study in Japan. Twenty-five-year experience in cardiovascular and all-causes deaths.

Within the Seven Countries Study two Japanese cohorts of men aged 40-59 were enrolled, one from the farming village of Tanushimaru (n = 508) and the other from the fishing village of Ushibuka (n = 502), both located in Kyushu. Cardiovascular risk factors were measured at entry and 10 years later in the survivors. The 25-year death rate for all causes was 30% higher in Ushibuka than in Tanushimaru (p < 0.001) and higher also from specific causes except for violence. Baseline differences in the levels of age, blood pressure, serum cholesterol, smoking habits, body mass index and heart rate explained only 19% of the difference in all-cause mortality between the two towns. Multivariate models from data of the pooled cohorts showed that age was a significant predictor of coronary heart disease, stroke, cancer, all other causes and all-cause mortality. Cigarette smoking predicted coronary heart disease, cancer and all-cause mortality. Systolic blood pressure predicted coronary heart disease, stroke and all-cause mortality. Serum cholesterol, body mass index and heart rate predicted none of these five causes of death. Changes in systolic blood pressure during the first 10 years of follow-up were directly related to deaths between 10 and 25 years of follow-up, significantly improving the predictive power of the multivariate model. Changes in the other risk factors did not contribute, however, to improved prediction.

Adult↗
PubMed1995

Association of hyperinsulinemia and serum free fatty acids with serum high density lipoprotein-cholesterol.

A total of 155 Japanese subjects (79 men and 76 women) who were classified as having normal or borderline glucose tolerance, according to the criteria for the 50-g oral glucose tolerance test (GTT) of the Japanese Diabetes Society, were analyzed for factors related to serum high density lipoprotein (HDL)-cholesterol concentration, especially the responses of insulin and free fatty acid (FFA) after a glucose challenge. In men, significant negative univariate correlations were observed with body mass index (P < 0.01), the summed values of triceps and subscapular skin-folds (P < 0.01), serum insulin concentration at all time intervals, and serum FFA at 30 and 60 min of GTT. Serum insulin at 60, 120, and 180 min, sum insulin, and FFA at 30 and 60 min of GTT were significantly related to serum HDL-cholesterol after adjustment for body mass index and triglyceride concentration. Multiple linear regression analysis with the step-forward method showed that sum insulin (P < 0.01), FFA at 60 min of GTT (P < 0.001), and alcohol consumption (P < 0.01) were independently related to serum HDL-cholesterol concentration. Only the triglyceride concentration was inversely correlated (P < 0.05) with HDL-cholesterol concentration in women. These data indicate that both insulin and FFA concentration, as markers of insulin resistance, apparently influence on HDL kinetics in men, but not in women. The lack of this association in women was appeared to related to the degree of obesity.

Adult↗
PubMed1994

Possible gene dose effect of a mutant cardiac beta-myosin heavy chain gene on the clinical expression of familial hypertrophic cardiomyopathy.

We have examined for a mutation in the cardiac beta myosin heavy chain gene from Japanese patients with familial hypertrophic cardiomyopathy. A missense mutation due to a G to A transition in codon 935, leading to a replacement of Glu with Lys, was found in one patient. Family members of this patient were then examined. It was revealed that both the proband and his elder brother, who was also a symptomatic patient, were homozygous for the mutation. The proband eventually died of intractable heart failure, and his brother died suddenly in their thirties. On the other hand, his parents, who were first cousins and heterozygous for the mutation, had cardiac hypertrophy without clinical symptoms. His elder sister was also heterozygous for the mutation, however, she did not manifest with cardiac hypertrophy. These observations suggest a gene-dose-like effect of the mutant cardiac beta myosin heavy chain gene on the clinical manifestation of familial hypertrophic cardiomyopathy.

Adenine↗
PubMed1994

Therapeutic management of dilated cardiomyopathy.

The therapeutic approach to dilated cardiomyopathy (DCM) still remains nonspecific and symptomatic, since no specific etiology is identified. Nevertheless, the recent introduction of angiotensin converting enzyme (ACE) inhibitors and beta-blockers greatly improved the treatment of DCM. The poor prognosis of patients with DCM encourages maximal aggressive attempts to prevent progression of ventricular dysfunction rather than to wait for treatable symptoms. To achieve this goal, vasodilators, particularly ACE inhibitors, now appear to be essential for the treatment of DCM. Digitalis is added unless contraindicated by adverse effects. Diuretics should be used only to relieve congestive symptoms. In the presence of sinus tachycardia or ventricular arrhythmias, beta-blockers are the next choice in our practice. When congestive symptoms or low output state are not controlled with vasodilators, diuretics, and digitalis, inotropic agents are indicated, with or without mechanical assist devices. For severely ill patients unresponsive to maximal medical management, heart transplantation is needed.

Adrenergic beta-Antagonists↗
PubMed1994

Nonsurgical correction for thrombosis of a St. Jude Medical tricuspid prosthesis: report of a case.

A 43-year-old woman with rheumatic heart disease underwent replacement of the aortic, mitral, and tricuspid valves using three SJM prostheses. Despite adequate warfarin therapy, routine cineradiography performed on the 40th postoperative day showed one of the leaflets of the tricuspid prosthesis to be "stuck" in the semiclosing position. A thrombosis of the tricuspid prosthesis was successfully treated with a urokinase infusion and mechanical thrombolysis using a pacemaker, following which normal valve function was restored.

Adult↗