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Biomedical subjects

H Toshima

Publications and source records attributed to H Toshima.

At least 19 recordsLinked to original sources

Adult coronary artery disease probably due to childhood Kawasaki disease.

We have surveyed adult survivors of childhood Kawasaki disease (KD) who had coronary artery disease that could be ascribed to KD. In response to questionnaires sent to cardiologists throughout Japan, 21 patients (17 men, 4 women, aged 20-63 years) with coronary lesions and a definite (2) or suspected (19) history of KD were reported. 5 patients had presented with acute myocardial infarction, 6 previous myocardial infarction, 9 angina pectoris, and 1 dilated cardiomyopathy. 16 patients had obstructions in two or more coronary arteries. 3 had died and 18 were alive with serious sequelae (mitral regurgitation, arrhythmias, congestive heart failure). Childhood KD should be included in the differential diagnosis of coronary artery disease in young adults.

Adult

Novel missense mutation in cardiac beta myosin heavy chain gene found in a Japanese patient with hypertrophic cardiomyopathy.

We have analyzed the exon 9, 13, 14, 15, and 16 of cardiac beta myosin heavy chain gene in 96 Japanese patients with hypertrophic cardiomyopathy by using PCR-DNA conformation polymorphism analysis. The analysis revealed a sequence variation of the exon 16 in one patient. The sequence variation of a G to C transversion with replacement of Asn by Lys at the codon 615 was confirmed by sequencing and by dot-blot hybridization with an allele-specific oligonucleotide probe. Because the missense mutation was found at the residue conserved through birds to humans, this mutation was suggested to be a cause of hypertrophic cardiomyopathy in the patient. This is the first report of a mutant cardiac beta myosin heavy chain gene in the Japanese population.

Amino Acid Sequence

Point mutations in mitochondrial DNA in patients with hypertrophic cardiomyopathy.

Recent advances suggest that mutations in nuclear DNA are involved in the etiology of autosomal dominant hypertrophic cardiomyopathy. Mitochondria have their own DNA, and mutations in mitochondrial DNA have been shown to contribute to the genesis of various diseases. In this study, we developed rapid sequencing methods with the use of a fluorescence-based sequencing system and analyzed total mitochondrial DNA of seven patients with nonautosomal dominant hypertrophic cardiomyopathy. Multiple point mutations were observed in all patients with hypertrophic cardiomyopathy, although some of them were common among the subjects examined and the others are unique to each subject. Point mutations in transfer RNA genes were observed in five of the seven patients, and point mutations that replaced conserved amino acids were also observed. These mutations may result in the impairment of mitochondrial function. According to these results, mutations in mitochondrial DNA may contribute to the genesis of some cases of nonautosomal dominant hypertrophic cardiomyopathy, and our methods may be useful for the detection of point mutations in mitochondrial DNA.

Adult

Therapeutic effect of oral dipyridamole on myocardial perfusion and cardiac performance in patients with hypertrophic cardiomyopathy.

Recent studies have indicated that myocardial ischemia could occur and could play an important role in the pathophysiology of patients with hypertrophic cardiomyopathy (HCM). We therefore investigated whether or not dipyridamole--a selective coronary vasodilating agent--could favorably modify myocardial perfusion and the clinical manifestations in 20 patients with HCM (19 nonobstructive and one mildly obstructive) with an average age of 50 years. Oral dipyridamole, 150 mg/day for 2 weeks, prevented reversible perfusion defects initially observed in six patients on baseline exercise thallium-201 (201TI) scintigraphy and significantly increased the 201TI clearance (40 +/- 13% to 44 +/- 12%), while one patient developed new reversible perfusion defects. There were significant increases in echocardiographic fractional shortening and treadmill exercise time and reductions in cardiac size and supraventricular arrhythmias with dipyridamole therapy. These observations suggest that coronary vasodilation with dipyridamole may improve myocardial perfusion and cardiac function in patients with HCM.

Administration, Oral

Beneficial antiarrhythmic effect of beta-blockade in patients with dilated cardiomyopathy.

Antiarrhythmic effects of beta-blockade (BB) in patients with dilated cardiomyopathy were compared with those of various antiarrhythmic agents using ambulatory Holter monitoring. The BB therapy effectively suppressed ventricular extrasystoles (VEs) in 85% of patients, as evidenced by improvement in Lown's grade or a reduction in the number of the highest grade VEs greater than 50%. In contrast, conventional antiarrhythmic agents, except flecainaid and amiodarone, were poorly effective in suppressing VEs. BB therapy gradually increased left ventricular fractional shortening (16 +/- 6% to 22 +/- 12%) and improved 12-month survival rates as compared with those receiving conventional therapy (93 vs 69%). This antiarrhythmic potency seemed to be an additional therapeutic efficacy of BB in the management of patients with dilated cardiomyopathy, which frequently associated with serious VEs.

Adrenergic beta-Antagonists

Postoperative erythroderma after cardiac operations. The possible role of depressed cell-mediated immunity.

Erythroderma as a manifestation of graft-versus-host disease after cardiac operations with blood transfusion may occur more frequently in Japan than in other countries. We have seen this problem in five patients who, after heart operations, died with symptoms and signs characteristic of graft-versus-host disease: cutaneous eruption, fever, diarrhea, leukopenia associated with agranulocytosis, and liver dysfunction. In the three patients seen most recently, skin biopsy showed findings similar to those of graft-versus-host disease after bone marrow transplantation. In addition, immunologic investigation showed remarkable differences in the findings in these patients and in those who did not have a graft-versus-host disease-like syndrome after cardiac operations. In particular, interleukin-2 production in response to mitogen stimulation was markedly diminished after operation in our patients, and the ratio of OKT4+ cells to OKT8+ cells in peripheral blood was low, reflecting increased numbers of OKT8+ cells after the occurrence of symptoms. The results raise the possibility that transient depression of cellular immunity after cardiac operations with blood transfusion may contribute to the occurrence of postoperative acute graft-versus-host disease.

Aged

Vitamin E deficiency has a pathological role in myocytolysis in cardiomyopathic Syrian hamster (BIO14.6).

This study revealed the occurrence of vitamin E deficiency in the myocardium of 60-day-old Syrian cardiomyopathic hamsters (BIO14.6), and that this deficiency might be related to the increase in lipid peroxide. Vitamin E administration for ten days effectively restored creatininekinase activity and decreased the lipid peroxide content in the myocardium, returning these to normal control levels (F1b). These results indicate that vitamin E deficiency, possibly combined with oxidative stress in the early cardiomyopathic stage plays an important role in initiating the pathogenesis of myocardial lesions.

Animals

New noninvasive assessment of regional left ventricular function by digital subtraction angiography without the use of contrast medium.

We have developed a new noninvasive method to evaluate regional left ventricular (LV) function by digital subtraction angiography (DSA) without the use of contrast medium. DSA images of the left ventricle with and without contrast medium were obtained from 35 patients with anterior myocardial infarction (MI) and from 35 control subjects. Using an image-processing computer, regional LV time-density curves were constructed for one cardiac cycle. Regional LV time-density curves obtained from DSA without the use of contrast medium presented a pattern similar to those from intravenous DSA. The amplitude of regional LV time-density curves in patients with MI decreased along with increasing severity of regional wall motion abnormality assessed by conventional left ventriculography. In attempting semi-quantitative evaluation by DSA without the use of contrast medium, the regional wall motion index (RWI) in the 6 segments of the left ventricle was calculated by normalizing segmental density changes to the maximal segmental density changes. When compared with control subjects, patients with MI have significantly lower RWIs in the anterolateral and apical regions. RWI showed a good correlation with the regional ejection fraction (REF) obtained from intravenous contrast DSA (r = 0.83). RWI decreased with increasing severity of regional wall motion abnormality by qualitative analysis in conventional left ventriculography, being consistent with REF. The diagnostic accuracy of RWI therefore seemed to be comparable to that of REF derived from intravenous contrast DSA. These results indicate that computerized analysis of DSA without the use of contrast medium is a valuable noninvasive method for semi-quantitative assessment of regional LV function.

Adult

Norepinephrine inhibits human natural killer cell activity in vitro.

The effect of norepinephrine on human NK cell activity was investigated using a flow cytometry assay. NK cell activity was found to be inhibited by direct addition of norepinephrine to lymphocyte/target cell mixtures in a dose-dependent fashion. This inhibitory effect of norepinephrine was blocked by propranolol but not by atenolol. The results suggest that norepinephrine has a negative influence on NK cell activity and that the effect of norepinephrine is mediated via beta 2-adrenoceptors.

Atenolol

[Cardiac mast cells in myocardial diseases].

Mast cells play a role in inflammation and immunological reactions. Cardiac mast cells with their granules are demonstrated easily by toluidine blue staining. We evaluated cardiac mast cells in endomyocardial biopsy specimens in patients with acute myocarditis (n = 17), idiopathic dilated cardiomyopathy (n = 17), idiopathic hypertrophic cardiomyopathy (n = 17) and control subjects (n = 12). Cardiac mast cells increase to an extreme degree in patients with acute myocarditis (2.4 counts/mm2) and increase relatively in patients with idiopathic dilated cardiomyopathy (1.4 counts/mm2). Patients with idiopathic hypertrophic cardiomyopathy (0.4 counts/mm2) were similar to control subjects (0.5 counts/mm2). Cardiac mast cells increased in accord with the severity of cellular infiltration and of interstitial fibrosis except for some cases with very severe fibrosis. In the acute myocarditis group, cardiac mast cells were well demonstrated in the early stage of the illness. But degranulations of mast cells did not give us any significant information in this study. Evaluation of cardiac mast cells will provide us with a new aspect in studying primary myocardial diseases.

Adolescent

[Quantitative analysis of myocardial fibrosis in myocardial biopsies--a comparison between computer analysis and point counting method].

To select an appropriate method to analyze quantitatively myocardial fibrosis in myocardial biopsies, two methods, the computer analysis and the point-counting method observed at magnifications of x200 and x400, were compared. Our targeted points of examination were the accuracy and reproducibility of these methods. Twenty patients (10 with dilated cardiomyopathy and 10 with hypertrophic cardiomyopathy) were randomly selected, and the percent area of myocardial fibrosis in myocardial biopsies obtained from the right ventricular septum was measured by both the computer analysis and the point-counting method. Two observers measured the same area twice on the different days, independently. In the area of analysis, the endocardium was excluded to avoid the observer's bias. By comparing the data obtained from two observers, it was shown that the point-counting method tended to give a larger mean value and standard deviation than the computer analysis method, but that the latter indicated better reproducibility than the former. Our result showed that the degree of myocardial fibrosis varied according to methods of analysis and observer's experiences. It is recommended that the comparison of myocardial fibrosis should be made only when the methods of analysis of fibrosis are identical.

Cardiomyopathy, Dilated

Decreased coronary vasodilatory capacity in hypertrophic cardiomyopathy determined by split-dose thallium-dipyridamole myocardial scintigraphy.

Split-dose thallium-dipyridamole myocardial scintigraphy was performed in patients with nonobstructive hypertrophic cardiomyopathy (HC) who had angiographically normal coronary arteries. The dipyridamole-induced increases in thallium-201 uptake, calculated to evaluate coronary vasodilatory capacity, were significantly lower in 30 patients with HC than in 13 control subjects (177 +/- 58 vs 281 +/- 46%) and the reductions were observed in both the septal and lateral segments. The reductions of the septal segment in HC patients were significantly greater than those in 10 hypertensive patients with comparable degrees of septal hypertrophy. Of patients with HC, 16 had increases in thallium uptake well below the normal range. Compared with those having normal increases, these patients had significantly lower exercise duration (11 vs 15 minutes), with 33% having ST depression develop at a workload less than or equal to 80 watts. These data indicate that approximately one-half of patients with HC have impaired coronary vasodilatory capacity that could be an important pathophysiologic abnormality of HC resulting in the development of myocardial ischemia and the impairment of cardiac performance during exercise.

Adolescent