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Biomedical subjects

H Mabuchi

Publications and source records attributed to H Mabuchi.

At least 145 records · Page 8Linked to original sources
PubMed1996

Clinical features of prognosis of Japanese patients with anomalous origin of the coronary artery.

Anomalous origin of the coronary artery can lead to angina pectoris, acute myocardial infarction or even sudden death in the absence of atherosclerosis. However, in Japan, this anomaly is usually treated medically rather than surgically. To clarify the clinical features of anomalous origin of the coronary artery in Japanese and the prognosis of such patients who are treated medically, we reviewed 56 patients with anomalous origin of the coronary arteries. The mean age of these patients was 55.9 +/- 11.5 years. Anomalous origin of the right coronary artery from the left sinus of Valsalva was seen most frequently (78.6%). In contrast, we found no cases of anomalous origin of the left coronary artery from the right sinus of Valsalva traversing between the aorta and the pulmonary trunk. A history of syncope (14.3%) and aorta regurgitation (21.4%) was frequent and serious complications during exercise stress testing occurred in 5 patients. These patients were treated medically, such as by limiting exercise or by the oral administration of medicine. During the follow up period (mean 5.6 +/- 4.2 years), death directly related to anomalous origin of the coronary artery was not found despite the lack of surgical treatment. Our results suggest that the prognosis of these middle-aged-to-elderly patients without atherosclerosis is relatively good, despite the lack of surgical treatment.

Adult↗
PubMed1996

[Cholesteryl ester transfer protein (CETP) deficiency and increased HDL cholesterol levels (hyperalphalipoproteinemia)].

Four different CETP gene mutations have been identified as causes of increased levels of HDL cholesterol by us and other investigators; two splice donor site mutations involving intron 14, one missense mutation of D442G in exon 15, and one nonsense mutation of Q309X in exon 10. Two splice donor site mutations are G(+1)-to-A transition (Int14A) and T insertion at +3 position (Int14T), and both mutations result in null phenotype as well as a nonsense mutation. By contrast, the D442G mutation is partially defective in plasma CETP activity. Both Int14A and D442G are common mutations in the general Japanese population with high frequencies of the heterozygotes of 1% and 7%, respectively. Heterozygous CETP deficiency is sufficiently common to explain 5% of the variation in HDL-C level in the general Japanese population, in addition to well-known environmental factors. CETP common mutations may be useful for risk-assessment of coronary heart disease, as a negative and genetic risk factor.

Carrier Proteins↗
PubMed1995

Noninvasive prediction of coronary atherosclerosis by quantification of coronary artery calcification using electron beam computed tomography: comparison with electrocardiographic and thallium exercise stress test results.

OBJECTIVES: This study was designed to compare the usefulness of electron beam computed tomography for prediction of coronary stenosis with that of electrocardiographic (ECG) and thallium exercise tests. BACKGROUND: Electron beam computed tomography can quantify coronary calcifications; however, its clinical value has yet to be established. METHODS: Using the volume mode of electron beam computed tomography, we studied 251 consecutive patients who underwent elective coronary angiography because of suspected coronary artery disease and compared the results with those of ECG and thallium exercise tests. The total coronary calcification score was calculated by multiplying the area ( > or = 2 pixels) of calcification (peak density > or = 130 Hounsfield units) by an arbitrarily weighted density score (0 to 4) based on its peak density. The mean of two scans was log transformed. RESULTS: Calcification was first noted in women in the 4th decade of life, approximately 10 years later than its occurrence in men. Among patients with advanced atherosclerosis (two- and three-vessel disease), calcification scores were uniformly high in women but ranged widely in men. Nine percent of patients with significant stenoses ( > or = 75% by densitometry) had no calcification. The calcification scores of patients with significant stenosis in at least one vessel were significantly higher than those of patients without significant stenosis in the study group as a whole and in most patient subgroups classified according to age and gender. A cutoff calcification score for prediction of significant stenosis, determined by receiver operating characteristic curve analysis, showed high sensitivity (0.77) and specificity (0.86) in all study patients; sensitivity was similarly high even in older patients ( > or = 70 years) and was enhanced in middle-aged patients (40 to < or = 60 years). The difference in specificity between calcification scores and ECG exercise test results had borderline significance (p = 0.058) and that between calcification scores and thallium test results was significant (p = 0.001). The latter difference became small but remained significant (p = 0.01) even after the reevaluation of thallium test results in light of each subject's clinical data. CONCLUSIONS: Quantification of coronary artery calcification with electron beam computed tomography noninvasively predicted angiographically confirmed coronary stenosis. Results obtained with this method were at least as useful and potentially better in some patient groups than those obtained with thallium and ECG exercise testing.

Adolescent↗
PubMed1995

Mutations causing high basal level transcription that is independent of transcriptional activators but dependent on chromosomal position in Saccharomyces cerevisiae.

Two single (bel2 and bel4) and two double (bel3 bel7 and bel5 be16) mutations causing enhanced transcription of a gene fusion, consisting of the open reading frame of PHO5 connected to the HIS5 promoter (HIS5p) integrated at the ura3 or leu2 locus, were isolated from a gcn4-disrupted mutant of Saccharomyces cerevisiae. The PHO5 gene, encoding repressible acid phosphatase, in the HIS5p-PHO5 construct was derepressed under amino acid starved conditions by the action of the transcriptional activator Gcn4p. The bel mutants showed temperature-sensitive cell growth and/or cell aggregation. All the mutants except bel4 also showed high levels of transcription of an intact PHO5 DNA integrated at the URA3 locus in the absence of the cognate transcriptional activator, Pho4p, and in the absence of upstream activating sequences of PHO5. The HIS5 and PHO5 genes at their original chromosomal positions were, however, not affected by the bel2 mutation. The BEL2 gene was found to be identical with SIN4/TSF3, mutations in which cause high levels of transcription of the HO and GAL genes in the absence of their respective transcriptional activators, Swi5p and Gal4p. The effect of the bel2/sin4/tsf3 mutation on PHO5 transcription was additive with the Pho4p function. Thus the effect of the bel2/sin4/tsf3 mutation is dependent on the position of PHO5 in the chromosome and independent of Pho4p and Gen4p activation.

Alleles↗
PubMed1995

Coronary artery bypass grafting in familial hypercholesterolemia.

Familial hypercholesterolemia is an autosomal dominant disorder caused by a mutation of the gene for the low-density lipoprotein receptor and is characterized by rapidly progressing coronary atherosclerosis. We assessed the long-term results of coronary artery bypass grafting performed during the past 13 years in 62 patients with heterozygous familial hypercholesterolemia, whose mean plasma total and low-density lipoprotein cholesterol level was 327 mg/dl, respectively. The patients had severe coronary atherosclerosis, with coronary stenosis index of 19.7, and the prevalence of extracoronary atherosclerotic lesions was 27%. Sixty-one patients underwent successful coronary artery bypass operation, with an average of 2.5 grafts, and the coronary stenosis index decreased to 7.1. After operation, all patients consumed a cholesterol-lowering diet and received drug therapy with pravastatin, probucol, or cholestyramine. Seven patients who were resistant to drug therapy were treated with plasma low-density lipoprotein apheresis. The cholesterol-lowering therapy reduced plasma total cholesterol level by 37%, low-density lipoprotein cholesterol level by 42%, and low-density lipoprotein/high-density lipoprotein cholesterol ratio by 37% (p < 0.001). During the follow-up period (mean, 52 months; range, 10 to 157 months), there was no cardiac death, but three patients died of malignant disease. The actuarial survival rate was 95% at 5 years and 89% at 12 years after operation. The actuarial freedom from recurrent angina was 90% at 5 years and 53% at 11 years after operation. Four patients underwent reoperation, an average of 8 years postoperatively, because of vein graft atherosclerosis. In spite of severe coronary atherosclerosis, these patients with familial hypercholesterolemia showed good long-term outcome after coronary artery bypass operation. The present findings suggest that aggressive use of arterial grafts, intensive cholesterol-lowering drug therapy, and low-density lipoprotein apheresis may be useful in patients with familial hypercholesterolemia.

Actuarial Analysis↗
PubMed1995

Effects of angiotensin-converting enzyme inhibitor and aldosterone antagonist on myocardial collagen in cardiomyopathic hamsters.

To examine the effects of angiotensin-converting enzyme (ACE) inhibitor and aldosterone antagonist on myocardial collagen in the cardiomyopathic hamster, the collagen concentration was measured by determining the hydroxyproline concentration, and the ratio of type I to type III collagen (type I/III ratio) was measured by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Five-week-old Bio14.6 cardiomyopathic hamsters were treated with the ACE inhibitor captopril (20 mg/kg per day) or the aldosterone antagonist K-canrenoate (20 mg/kg per day) in drinking water for 20 weeks, and the collagen concentration and type I/III ratio at 25 weeks were compared with those in 25-week-old untreated Bio14.6 and normal F1b hamsters. The collagen concentration markedly increased and the type I/III ratio significantly decreased (ie, type III collagen dominant) in untreated Bio14.6 compared with F1b at 25 weeks. Captopril and K-canrenoate treatment significantly reduced the collagen concentration and reversed the changes in the type I/III ratio in cardiomyopathic hamster. These results suggest that ACE inhibitor and aldosterone antagonist improve myocardial collagen in the cardiomyopathic hamster, not only quantitatively but also qualitatively, and that the mechanism of this improvement may be related to the cardiac renin-angiotensin-aldosterone system.

Aging↗
PubMed1995

Ultrafast computed tomography in the diagnosis and evaluation of anomalous origin of the right coronary artery.

Anomalous origin of the right coronary artery may lead to myocardial ischemia despite the absence of atherosclerosis. We report the case of a 52-year-old man who was admitted to our hospital with exertional chest discomfort and palpitations. An anomalous origin of the right coronary artery was demonstrated by coronary angiography. There was no evidence of atherosclerosis in either the left or right coronary arteries. However, detailed information regarding the proximal portion of the anomalous artery was not acquired by coronary angiography. In this patient, ultrafast computed tomography (UFT) revealed an acute angle takeoff of the anomalous right coronary artery from the aorta. Furthermore, the proximal portion of the right coronary artery traversed the aorta and pulmonary trunk. This case illustrates that UFT is useful for detecting an anomalous origin of the coronary arteries and evaluating the mechanism of myocardial ischemia in patients with anomalous origin of the coronary arteries.

Coronary Angiography↗
PubMed1995

[Carbon-11 labeled diacylglycerol for signal transduction imaging by positron CT: evaluation of the quality and safety for clinical use].

To elucidate the synaptic transmission in the neural system, we have been developing fundamental studies for intracellular signaling. For clinical application of carbon-11 labeled diacylglycerol (1-[1-11C]butyryl-2-palmitoyl-rac-glycerol: 11C-DAG) using positron emission computed tomography (PET), we evaluated the quality and the safety of 11C-DAG as the solution for injection. As a result, 11C-DAG was synthesized within 50 minutes, including the preparation step for injection. The half life time and energy spectrum of 11C-DAG were the same as the physical character of carbon-11, and other radioisotopes were not detected. In the quality control, 11C-DAG solution was negative in the examination of bacterial contamination and the pyrogen test in three successive synthesis procedures. In the acute toxicity test by administration of 11C-DAG and 100 mumol/kg of non-radioactive DAG to the rat intravenously, the systemic condition of the rat was not changed and no abnormalities were found in any organ 24 hours after administration. These findings indicated the safety of 11C-DAG solution. Clinical application of 11C-DAG using positron emission tomography may be useful to elucidate the dysfunction of intracellular signaling in disorders of higher cortical function such as Alzheimer disease.

Animals↗
PubMed1995

[Molecular genetics of cholesterol transport and cholesterol reverse transport disorders (familial hypercholesterolemia and CETP deficiency), and coronary heart disease].

Familial hypercholesterolemia (FH) is a disorder of LDL receptor abnormalities, and the resultant high-LDL-cholesterolemia produces atherosclerosis. More than 150 different mutations in the LDL receptor gene have been reported in the world. Seven variants of the LDL receptor gene have been identified in our laboratory. These seven mutants in 85 patients from 31 families accounted for only 15.5% of the FH cases. LDL receptor gene abnormalities are highly heterogenous in Japan, and the variation of the LDL receptor mutant may determine the severity of hypercholesterolemia and coronary heart disease in FH. A serum HDL above 60 mg/dl is a negative risk factor for coronary atherosclerosis. We found that familial hyperalphalipoproteinemia can be produced by CETP deficiency due to a CETP gene. Two common mutants of the CETP gene produce a CETP deficiency and resultant antiatherogenic lipoprotein pattern (i.e. hyper-HDL-cholesterolemia and hypo-LDL-cholesterolemia), and the frequency of the mutant allele is more than 1 in 10 subjects in Japan. Finally, we found unique patients with double heterozygotes of FH and CETP deficiency. We found 16 double heterozygotes of the LDL receptor gene and CETP gene. Four of the 16 patients showed myocardial infarction and 4 showed angina pectoris. These findings suggest that the atherogenicity of hyper-LDL-cholesterolemia in FH is more powerful than antiatherogenicity of hyper-HDL-cholesterolemia in CETP deficiency.

Carrier Proteins↗
PubMed1995

[A quantitative evaluation of coronary steal phenomenon in coronary artery-pulmonary artery fistula: case report].

A 67-year-old woman was admitted to our hospital with a complaint of anterior chest pain on exertion. Auscultation disclosed a continuous murmur and exercise electrocardiography revealed positive ischemic ST change. Coronary angiography showed a large left coronary fistula and a small right coronary fistula into the main pulmonary artery. To evaluate the influence of the fistula on coronary circulation, we measured blood flow in the left anterior descending artery (LAD) and in the fistula artery using a 0.014 inch Doppler guide wire. Before surgery, blood flow in the LAD decreased during rapid atrial pacing (130 bpm) but that in the fistula remained constant. After the surgery, there was no remarkable decrease in blood flow in the LAD during rapid atrial pacing (130 bpm), and the preoperative reduction ratio was calculated as 24% compared with postoperatively. These findings suggest that coronary steal phenomenon was involved in myocardial ischemia in this patient.

Aged↗
PubMed1995

[EBER-1 expression in salivary glands of Sjögren's syndrome].

EB virus-encoded small nuclear RNAs (EBERs) which present in large numbers during persistent infection, are known to stably bind to SSB/La antigen, leading to speculation that EBV may be involved in the pathogenesis of primary Sjögren's syndrome (1 degree SjS). Although studied by many investigators serologically, immunohistochemically and molecular biologically, this remains controversial. In situ hybridization study for EBER-1 showed positive hybridization in ductal epithelial cells in nine of eighteen salivary glands (SGs). Hybridization was more intense in ducts surrounded by infiltrating mononuclear cells (MNCs). Positive hybridization was also seen in infiltrating MNCs in eight 1 degree SjS SGs. These results indicate that EBV plays some pathogenic roles in some cases of 1 degree SjS through induction of SSB/La antibody and impairment of lymphocytes.

Autoantigens↗