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Biomedical subjects

S Murata

Publications and source records attributed to S Murata.

At least 91 records · Page 5Linked to original sources

Left ventricular volume predicts postoperative course in patients with ischemic cardiomyopathy.

BACKGROUND: The left ventricular end-systolic volume index (LVESVI) helps to predict postoperative left ventricular function in patients with ischemic cardiomyopathy. METHODS: We retrospectively assessed the ability of preoperative variables to predict death and the development of postoperative congestive heart failure in 41 patients with a preoperative ejection fraction of less than 0.30. RESULTS: A preoperative LVESVI of greater than 100 mL/m2 was identified as an independent predictor of death by Cox's proportional hazards model. Diabetes and a preoperative LVESVI of greater than 100 mL/m2 were independent predictive risk factors for the development of postoperative congestive heart failure. Postoperative congestive heart failure developed in 2 of the 23 patients (8.7%) who had a preoperative LVESVI of less than 100 mL/m2 and in 10 of the 16 patients (62.5%) who had a preoperative LVESVI of greater than 100 mL/m2. The actuarial survival rate during follow-up in patients who had a preoperative LVESVI of less than 100 mL/m2 was significantly greater than that in patients who had a preoperative LVESVI of greater than 100 mL/m2. The actuarial rate of freedom from congestive heart failure during the follow-up period also was greater in patients who had a preoperative LVESVI of less than 100 mL/m2. CONCLUSIONS: Our results suggest that the preoperative LVESVI predicts the development of postoperative congestive heart failure and the actuarial survival rate in patients with ischemic cardiomyopathy.

Aged↗

Alpha1-adrenoceptor subtypes and two receptor systems in vascular tissues.

The subtypes of alpha1-adrenoceptor are coexpressed in many tissues. We examined the relationship between coexpressed alpha1-adrenoceptor subtypes and their functions in blood vessels. Rat and rabbit aortas coexpressed three subtypes (alpha1A, alpha1B, alpha1D) and four subtypes (alpha1A, alpha1B, alpha1D, alpha1L), respectively. In rat aorta however, noradrenaline-induced contraction was mediated predominantly through the alpha1D subtype, and oxymetazoline produced alpha1B-mediated contraction. In rabbit aorta, concentration-response curves for noradrenaline were composed of two components (alpha1B and alpha1L-mediated), while oxymetazoline produced alpha1L-mediated contraction. Therefore, the inhibitory actions of some antagonists varied markedly among tissues and agonists. These results demonstrate diversity of the two receptor systems and suggest that the heterogeneity of physiological responses reflects the differences in functional subtypes among tissues and in their sensitivities to agonists and antagonists.

Adrenergic alpha-Agonists↗

Malignant schwannoma-derived cells support human skin mast cell survival in vitro.

We have recently observed mast cell infiltration in malignant schwannoma (MS) arising in the patient with von Recklinghausen's disease. To determine the cell to cell interactions between human skin mast cell (HSMC) and MS cell, we investigated the HSMC survival and the morphological changes when cultured with MS-derived cells isolated from the patient. Partially purified HSMCs obtained from normal adult skin and cutaneous neurofibroma by enzymatic digestion were cocultured with MS-derived cells on the coverslips. The number of HSMCs stained with crystal violet were directly counted by light microscope. HSMCs cocultured with MS-derived cell feeder layer revealed significantly increased HSMC survival compared to that with normal human skin fibroblast layer at 1 and 2 weeks. Conditioned medium of cultured MS-derived cell did not influence HSMC survival. In the morphology HSMCs cultured with MS-derived cells demonstrated spindle form in close contact with the adjacent MS-derived cells, suggesting cell to cell interactions. We failed to detect stem cell factor (SCF) mRNA in cultured MS-derived cell by RT-PCR. These results suggest that MS-derived cell is capable of supporting HSMC survival in vitro. Some factor(s) other than SCF, which is associated with direct contact between HSMCs and MS-derived cells, might relate to these observations.

Cell Survival↗

Cloning of hamster preproendothelin-1 cDNA and its expression in the heart.

To elucidate the pathophysiologic roles of endothelin-1 (ET-1) in the heart, we first cloned and sequenced a part of hamster preproET-1 cDNA from the heart of the CHF146 hamsters. The amino acid sequence has 89% homology to that of rat preproET-1 in the cloned part. The deduced hamster 21-residue mature ET-1 is identical to human, rat, canine, and mouse ET-1. In the next step we investigated the expression of preproET-1 mRNA in the failing heart of CHF146 hamsters. For this purpose, we used 46-week-old CHF146 hamsters and age-matched control healthy hamsters. Left ventricular (LV) + dP/dtmax was significantly lower in CHF146 hamsters than in control hamsters. LV end-diastolic pressure was significantly higher in CHF146 hamsters than in control hamsters, as was central venous pressure. These results suggested that the CHF146 hamsters developed congestive heart failure. The expression of preproET-1 mRNA was greatly enhanced in the LV of the CHF146 hamsters. Because it has been reported that ET-1 induces cardiac hypertrophy and injury to cardiac myocytes in addition to its potent positive inotropic and chronotropic actions, the present findings suggest that endogenous ET-1 plays pathophysiologic roles in the failing heart of CHF146 hamsters.

Amino Acid Sequence↗

Cardiovascular effect of a new 1,5-benzothiazepine derivative TA-993 in anesthetized dogs.

TA-993 is a new 1,5-benzothiazepine derivative having l-cis configuration and shows a potent antiplatelet aggregating action. We studied its cardiovascular effect in anesthetized dogs by using diltiazem as a reference compound. TA-993 (> or = 10 microg/kg, i.v.) significantly increased blood flows of common carotid, brachial, and femoral arteries. The peak of its effect was observed approximately 60 min after the administration, and the peak level was maintained until > or = 300 min after the administration. TA-993 (100 microg/kg, i.v.) slightly increased cardiac output in the same manner. However, TA-993 did not cause any persistent effects on arterial pressure, LVdP/dtmax, or vertebral, coronary, superior mesenteric, and renal blood flows. TA-993 caused concentration-dependent vasorelaxation in the isolated canine femoral artery contracted with 40 mM K+, but its potency was approximately 1/20 that of diltiazem. The increasing action of TA-993 on femoral blood flow was completely inhibited by pretreatment with hexamethonium in anesthetized dogs. These results indicate that TA-993 has a selective increasing action on common carotid, brachial, and femoral blood flows and suggest that the action is mediated by the autonomic nervous system.

Animals↗

Antithrombotic action of TA-993, a new 1,5-benzothiazepine derivative, in a canine model of femoral arterial thrombosis.

TA-993 is a novel 1,5-benzothiazepine derivative of l-cis configuration, having a potent antiplatelet action and an increasing action on femoral blood flow. We evaluated the antithrombotic effect of TA-993 in a canine model of femoral arterial thrombosis. Thrombus was induced by both application of direct anodal current to the femoral artery and partial occlusion of the artery. The partial occlusion by placing an adjustable occluder on the artery and the current application were carried out 40 and 60 min after the intraduodenal administration of drugs, respectively. In control dogs, complete sustained occlusion of the femoral artery due to thrombus occurred 55.4 +/- 9.2 min after the onset of current application. TA-993 (3 and 10 mg/kg) dose-dependently prolonged the time for occlusion. Aspirin (30 mg/kg) also prolonged it. TA-993, 10 mg/kg, significantly inhibited whole-blood aggregation 60 min after the administration with a weaker potency than that of aspirin (30 mg/kg), whereas 3 mg/kg of TA-993 did not. The inhibitory effect of TA-993 (10 mg/kg) on platelet aggregation was maintained for >7 h. Moreover, TA-993 (10 mg/kg) increased femoral blood flow in spite of the partially occluded condition. These results indicate that TA-993 has an antithrombotic effect on femoral arterial thrombosis and suggest that an increasing action on femoral blood flow of TA-993 is more relevant than its antiplatelet action to the antithrombotic effect in this model.

Animals↗

Pharmacologic profile of TA-606, a novel angiotensin II-receptor antagonist in the rat.

This study was carried out to characterize a novel angiotensin II-receptor antagonist, TA-606, (3-pentyloxy) carbonyloxymethyl-5-acetyl-2-n-propyl-3-[2'(1H-tetrazole-5-yl) biphenyl-4-yl]methyl-4,5,6,7-tetrahydro imidazo [4,5-c] pyridine-4-carboxylate hydrochloride, which is a newly synthesized prodrug of 606A. In anesthetized rats, 606A inhibited angiotensin II-induced pressor response with a median inhibitory concentration (IC50) of 6 microg/kg, i.v., and was 8 times more potent than EXP3174, an active metabolite of losartan. Bioavailability of TA-606 was 11 times higher than that of 606A in Sprague-Dawley rats, with consistent hypotensive potencies in spontaneously hypertensive rats (SHRs). In conscious renal hypertensive rats (RHRs) and conscious SHRs, TA-606 lowered the blood pressure without any effects on the heart rate, and its effective dose for 30 mm Hg (ED30) values were 0.14 and 0.21 mg/kg, p.o., respectively. The effect of TA-606 lasted > 10 h in both models. Moreover, the effect of TA-606 was approximately 30 and 10 times more potent than those of losartan in RHRs and SHRs, respectively. TA-606 did not affect the blood pressure in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. TA-606 given for 12 weeks attenuated the development of hypertension in stroke-prone SHRs. These results indicate that TA-606 is a potent angiotensin II-receptor antagonist with antihypertensive efficacy. Thus TA-606 is suggested to be a possible useful agent in the treatment of hypertension.

Angiotensin Receptor Antagonists↗

Detection of diaphragmatic defect as the cause of severe hepatic hydrothorax with magnetic resonance imaging.

Severe right-sided hepatic hydrothorax occurred in an 83-yr-old Japanese woman with a 7-yr history of cryptogenic liver cirrhosis. Transdiaphragmatic communication was indirectly suggested by rapid migration of dye (indocyanine green) from the peritoneal to the pleural space. Magnetic resonance imaging studies also demonstrated a diaphragmatic defect as a characteristic hypointense jet flow across the diaphragm on both T1- and T2-weighted sagittal scans. Although no firm treatment for hepatic hydrothorax has been established and direct demonstration of diaphragmatic defect with noninvasive imaging is extremely rare, testing for diaphragmatic integrity is meaningful to provide a radical or less invasive treatment. Magnetic resonance imaging, as well as color Doppler ultrasonography, may be useful for the detection of diaphragmatic defects as the cause of hepatic hydrothorax.

Aged↗

Transcatheter embolization of celiac artery pseudoaneurysm following pancreatico-duodenectomy for pancreatic cancer. A case report.

A case of transcatheter embolization of a celiac artery pseudoaneurysm in a 70-year-old man is reported. The pseudoaneurysm was considered to be the result of pancreatic anastomotic leakage and an intra-abdominal abscess following pancreaticoduodenectomy with irradiation of 66 Gy for pancreatic carcinoma. To avoid recanalization of the pseudoaneurysm due to retrograde blood flow, first all branches of the celiac artery were embolized with metallic coils, and then the celiac trunk was also occluded. Hepatic arterial flow was preserved by the right hepatic artery arising from the superior mesenteric artery. After the procedure, the patient had no noticeable complications associated with the embolization nor any recurrence of the pancreatic cancer, and he achieved a 2-year survival.

Aged↗

[HLA antigens are associated in seronegativity to cytomegalovirus(CMV)].

Cytomegalovirus(CMV) is ubiquitous in the world, but the rate of CMV antibody positivity (seropositivity) in adults varies geographically. In Japan, CMV seropositivity in adults in 90% and we perceived seronegative adults tend to remain seronegative in 10 years follow up study. We have performed HLA typing 125 seronegative healthy donors of 28 years and up (28-57, Ave.35), and the results were compared with those of healthy donors in same area and whole Japan (data from 10th HLA workshop). Incidence of HLA-A33 and HLA-Cw4 were significantly higher in seronegatives than control groups. This report suggests possible involvement of HLA type in CMV negativity.

Adult↗

[Intraoperative assessment of the ascending aorta by echogram during the CABG operation for the prevention of cerebral infarction].

While coronary artery bypass grafting operations (CABG), we started to use the echogram to evaluate the ascending aorta intraoperatively from December 1993. During a period from January, 1990, to June, 1995, 379 patients were treated with CABG. Intraoperative echogram was used in 127 cases (group I) and 252 cases unused (group II). The sites of the aorta for evaluation were following: site of cannulation, aortic clamping, and proximal anastomosis respectively. Depending on the echographical findings the operative procedures were changed as required. The incidence of postoperative cerebral embolism in group I was 0.8% (one patient) and in group II, 2.4% (6 patients). Although no significant difference was found in the cohort, rate of incidence in the group II was high. There were 4 cases who had significant atheromatous lesions clearly evaluated by echogram, which were not detected by palpation. We conclude that the intraoperative assessment of the ascending aorta by echogram is beneficial in prevention of cerebral infarction.

Aged↗

[Detection of apolipoproteins E5 and E7 by a widely used commercial ApoE IFE kit--evidence provided by genotyping].

The purpose of this study is to examine a possibility to detect apolipoprotein (apo) E5 and E7 isoproteins with a commercial kit widely used (Phenotyping Apo E IFE System, Jokoh Co. LTD., Tokyo) and to clarify the frequency of the rare alleles in Central Japan. A total of 1,445 subjects living in Central Japan (1,030 hemodialysis patients and 415 apparently healthy individuals) was phenotyped for apo E isoproteins with the kit using isoelectric focusing with immunoblotting. In 23 subjects, unique apo E4 isoproteins, which migrate more basically than apo E4 isoprotein, were found. These unique isoproteins were proved to be apo E5 or E7 isoproteins by PCR with restriction fragment length polymorphism and with amplification refractory mutation systems, respectively. No significant differences in the frequencies of apo E5 or apo E7 alleles were observed between healthy individuals and hemodialysis patients (0.011 vs. 0.018, NS). The frequencies of apo E5 and E7 alleles were 0.001 and 0.005, respectively, in healthy individuals, and 0.003 and 0.005, respectively, in hemodialysis patients. These data in Central Japan were consistent with those in Western Japan (Matsunaga, et al, Clin Genet, 1995). These results indicate that the commercial kit is applicable to detect the rare alleles, apo E5 and E7 alleles and that the frequencies of the rare alleles in Central Japan are similar to those in Western Japan.

Adult↗

Pharmacological profile of T-0201, a highly potent and orally active endothelin receptor antagonist.

The authors studied the pharmacological properties of N-(6-(2-(5-bromopyrimidin-4-yl)-4-(2-hydroxy-1, 1-dimethylethyl)benzensulfonamide sodium salt sesquihydrate (T-0201), a new nonpeptide endothelin (ET) receptor antagonist, in vitro and in vivo. In binding studies, T-0201 competitively antagonized the specific binding of [125I]-ET-1 to human cloned ETA receptors (the Ki value was 0.015 +/- 0.004 nM). T-0201 weakly inhibited [125I]-ET-1-binding to human cloned ETB receptors; the Ki value was 41 +/- 21 nM. T-0201 shifted the concentration-response curve of ET-1-induced contraction of the isolated rat aorta (ETA receptors) to the right (pA2 = 9.0 +/- 0.2). In the isolated rat trachea, a selective ETB agonist sarafotoxin S6c-induced contraction was inhibited by T-0201 (pA2 = 6.8 +/- 0.3). T-0201 also caused the inhibition of ET-1-induced contraction of the isolated rabbit pulmonary artery (pA2 = 5.7 +/- 0.3). In anesthetized rats, T-0201 (0.01-1 mg/kg) inhibited the pressor response to exogenous big ET-1 (1 nmol/kg i.v.), after both i.v. and p.o. administration, in a dose-dependent manner. The significant inhibitory effect of orally administered T-0201 on big ET-1-induced pressor response lasted for 4 hr at 0.1 mg/kg and for 8 hr at 1 mg/kg. Thus the present study demonstrates that T-0201 is a highly potent, long-lasting, orally active and selective ETA receptor antagonist.

Animals↗

[Postoperative follow-up of acute aortic dissection and the result of second operations].

Between January 1990 and March 1998, surgical treatment was performed in 75 patients with acute aortic dissection at Omiya Medical Center. Seventy-three patients (97%) of them were classified type A aortic dissection. Thirteen of them died due to hemorrhage (5 cases), cardiac failure (3 cases), visceral ischemia (3 cases) and others (2 cases) after the operation. Hospital mortality rate was 17.3%. Sixty-two survivors were followed up to 8 years. During the follow up period, five patients died due to pneumonia, gastric cancer, cardiac failure, brain hemorrhage and unknown event. Five-year survival rate including hospital death was 77% evaluated by Kaplan-Meier method. Second operations for the enlargement of residual false lumen with the entry were performed in 4 patients (6.5%) of 62 survivors. Second operations were also performed in other 6 patients referred to us from other hospitals because of the enlargement of false lumen. Nine of them survived (90%) and returned to their daily life.

Acute Disease↗

[Concomitant cardiac and pulmonary operation, the profits of not using cardio-pulmonary bypass].

We performed off pump CABG (coronary artery bypass grafting) and right upper lobectomy with R2a lymph nodes dissection on the patient suffered from both lung cancer in the right S1 and stenotic lesion in the left anterior descending artery. Because the coronary lesion was long-segmented one, it was not suitable for percutaneous transluminal coronary angioplasty. To perform absolutely curative operation for the lung cancer, CABG was undergone simultaneously under off pump condition. It is generally feared that the cardiovascular surgery under CPB may have adverse effect for the patient with malignant lesion. Off pump CABG is expected to avoid such disadvantage of CPB, and thought to be suitable method for such a patient as we present above.

Adenocarcinoma↗

KMD-3213, a novel alpha1A-adrenoceptor antagonist, potently inhibits the functional alpha1-adrenoceptor in human prostate.

KMD-3213, (-)-(R)-1-(3-hydroxypropyl)-5-[2-[[2-[2-(2,2,2-trifluoroethoxy)phe noxy]ethyl]amino]propyl]indoline-7-carboxamide, is a novel and selective alpha1A-adrenoceptor antagonist. The potency of this drug to antagonize functional alpha1-adrenoceptor-mediated contraction in human prostatic smooth muscle was evaluated and compared with that of other alpha1-adrenoceptor antagonists. KMD-3213 inhibited noradrenaline-induced contractions with an apparent pK(B) value of 9.45 +/- 0.039, indicating a potency similar to that of tamsulosin. The affinity of prazosin for prostatic alpha1-adrenoceptors is given as potency for the alpha1L-adrenoceptor with an estimated pA2 value of 8.84 +/- 0.044. The data obtained in this study suggest that KMD-3213, an alpha1A-adrenoceptor-selective antagonist, has strong affinity for the alpha1L-adrenoceptor in the human prostate.

Adrenergic alpha-1 Receptor Antagonists↗