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T Miyauchi

Publications and source records attributed to T Miyauchi.

At least 91 records · Page 5Linked to original sources
PubMed1998

Endothelin-converting enzyme and angiotensin-converting enzyme in failing hearts of rats with myocardial infarction.

We have previously reported that production of endothelin (ET)-1 is markedly increased in failing hearts of rats with chronic heart failure (CHF). It was also reported that the production of angiotensin II (Ang II) is increased in the failing heart. In this study we investigated both converting enzymes of the ET-1 system and the angiotensin system. We used left coronary artery-ligated rats as a model of CHF. The peptide level of ET-1 in the left ventricle (LV) was markedly higher in CHF rats than in control rats. In the LV, expression of preproET-1 mRNA was also markedly higher in CHF rats than in controls. The expression of endothelin-converting enzyme (ECE)-1 mRNA in the rats with CHF was similar to that in controls. Therefore, we believed that the increase in ET-1 production in the failing heart originated from an increase in preproET-1 production rather than increase in ECE. The expression of angiotensin-converting enzyme (ACE) mRNA in failing hearts of CHF rats was significantly higher than that of the sham-operated rats. The expression of angiotensinogen mRNA in failing hearts of these CHF rats was slightly higher than that of the sham-operated rats. This study suggests that there is a difference in the role of peptide synthesis between the ECE system and the ACE system in rats with CHF.

Angiotensinogen↗
PubMed1998

Prolonged exercise causes an increase in endothelin-1 production in the heart in rats.

Cardiac myocytes produce endothelin-1 (ET-1). ET-1 has potent positive inotropic and chronotropic effects. We investigated whether production of ET-1 in the heart is altered by prolonged exercise in rats. Rats ran on a treadmill for 45 min. Immediately after this exercise the heart and lungs were quickly removed. Control rats remained at rest during this 45-min period. Expression of preproET-1 mRNA in the heart was markedly higher in the exercised than in the control rats. The peptide level of ET-1 in the heart was also markedly higher in the exercised rats. Expression of endothelin type A- and type B-receptor mRNA and endothelin-converting enzyme mRNA in the heart did not differ between the groups. The peptide level of ET-1 and the preproET-1 mRNA level in the lungs of the exercised rats did not differ from those in the control rats. The present results show that production of ET-1 is markedly increased tissue specifically in the heart by exercise without appreciable changes in endothelin-converting enzyme and endothelin receptor expression. The present study suggests that myocardial ET-1 may participate in modulation of cardiac function during exercise.

Animals↗
PubMed1998

Exercise causes tissue-specific enhancement of endothelin-1 mRNA expression in internal organs.

Endothelin-1 (ET-1) is a potent vasoconstrictor peptide, which also potentiates contractions to norepinephrine in human internal mammary and coronary vessels. Exercise causes a redistribution of blood flow, i.e., the increase in working muscles that is partly attributable to a decrease in visceral blood flow. We hypothesized that exercise causes a tissue-specific increase in ET-1 expression in internal organs. We studied whether exercise affects expression of preproET-1 mRNA in the kidneys and lungs. The rats performed treadmill running (0% grade) for 45 min at a speed of 25 m/min. The plasma concentrations of ET-1, epinephrine, and norepinephrine were greater in the exercise rats than in the sedentary control rats. The expression of preproET-1 mRNA in the kidneys was markedly higher in the exercise rats than in the sedentary control rats, whereas that in the lungs did not differ between the two groups. Therefore, the present study provides a possibility that the exercise-induced increase in production of ET-1 in the kidneys causes vasoconstriction and hence decreases blood flow in the kidneys through its direct vasoconstrictive action and/or its indirect effect of enhancing vasoconstrictions to norepinephrine.

Animals↗
PubMed1998

Hypotensive effects of an angiotensin II type 1 receptor antagonist differ between exercised and sedentary rats aged from 4 to 19 weeks.

The hypotensive effects of an angiotensin II type 1 receptor antagonist TCV-116 were accelerated by swimming training in the early period of chronic administration in young rats. In the latter period, however, a severe decrease in blood pressure that appeared during long-term administration of TCV-116 was prevented by swimming training. Therefore exercise may contribute to the stabilization of blood pressure in young rats treated with TCV-116.

Angiotensin Receptor Antagonists↗
PubMed1998

Midcourse thallium-201 scintigraphy to predict tumor response in bone and soft-tissue tumors.

UNLABELLED: The purpose of this study was to assess the predictive power of 201TI scintigraphy in the midcourse of chemotherapy for the final tumor response to chemotherapy in malignant bone and soft-tissue tumors. METHODS: The 21 patients studied with 201TI scintigraphy were 14 males and 7 females (average age 39.8+/-22.1 yr; age range 8-74 yr). Planar scintigraphy was performed 15 min after injection of 111 MBq 201TI before chemotherapy, after the third chemotherapy cycle (midcourse) in all 21 patients and after the final chemotherapy cycle but before surgery in 11 patients. The 201TI uptake ratio was calculated by dividing the count density of the lesion by that of the contralateral normal area. The percent reduction of the 201TI uptake ratio calculated by 100 x [(prechemotherapy ratio - postchemotherapy ratio)/prechemotherapy ratio] in the midcourse was compared with that after the final course of chemotherapy, and it also was compared with the histologic response. RESULTS: In patients with histologically complete response [(CR), n=6] and with partial response [(PR), n=5], the percent reduction in 201TI uptake ratio after three cycles of chemotherapy was 64.1%+/-14.4% and 50.9% +/-10.5%, respectively. In patients with histologically no change [(NC), n=10], the percent reduction was 0.40%+/-18.2% after the third cycle; -5.3%+/-20.9% in four patients with full courses of chemotherapy (p < 0.0001 and p < 0.005 compared with the CR and PR groups, respectively). After the final cycle of chemotherapy, the percent reduction in 201TI uptake ratio was 68.6%+/-14.7%, 56.2%+/-6.1% and -0.3%+/-17.2% in the CR, PR and NC groups, respectively (NC versus CR, p < 0.0005; NC versus PR, p < 0.005). CONCLUSION: Thallium-201 scintigraphy performed in the midcourse of chemotherapy is predictive of the final response to chemotherapy that can be demonstrated histologically. Serial 201TI scintigraphy in the midcourse of chemotherapy is useful in assessing final chemotherapeutic response in the early stage of chemotherapy, and it helps clinicians when choosing the most appropriate treatment strategies in patients with bone and soft-tissue tumors.

Adolescent↗
PubMed1998

[Pryce type I interlobar pulmonary sequestration with anomalous return to the left inferior pulmonary vein].

A 50-year-old woman was examined because of chest discomfort. Chest X-ray films disclosed a tumorous shadow behind the heart. Chest computed tomography (CT) scans revealed a mass connected to the descending aorta, with increased blood flow in the left basal segment. The patient was admitted for further examination. Chest CT scans and cardioscintigrams were very useful as diagnostic tools, but the final diagnosis was made on the basis of angiography. An anomalous tortuous artery ran from the descending aorta into the left basal segment and returned to the left inferior pulmonary vein. The left pulmonary arterial trunk had no basal branch (A8-A10). A loop corresponding to the superior vein (V6) ran beneath the anomalous tortuous artery. To our knowledge, this is the second case of Pryce type-I interlobar pulmonary sequestration with anomalous return to the left inferior pulmonary vein to be reported in Japan. A left inferior lobectomy was performed. Histological finding from the excised tissues showed prominent interstitial fibrosis, atypical adenomatous hyperplasia, and atherosclerosis. Following surgery, the patient's PaO2 increased from 80.4 Torr to 95.8 Torr, suggesting that left inferior lobectomy was an appropriate treatment.

Bronchopulmonary Sequestration↗
PubMed1997

Abnormalities of sensory and memory functions in mice lacking Bsg gene.

Basigin is a highly glycosylated transmembrane protein belonging to the immunoglobulin superfamily. We used mutant mice lacking the basigin gene (Bsg) to investigate its involvement in learning and memory. Mutations were generated by the gene targeting method. Various kinds of learning and memory tasks were performed in mutant, hetero and wild type mice. The mutant mice showed worse performance than the wild and hetero mice in the Y-maze task, which assesses short-term memory, and in the water finding task, which examines latent learning, without any motor dysfunction. Moreover, the mutant mice showed less acclimation in the habituation task compared with the wild-type mice. The mutant mice were also more sensitive to electric foot-shock. These findings are consistent with the expression profile of basigin in the central nervous system. Thus, basigin may play an important role in learning and memory as well as in the sensory functions.

Animals↗
PubMed1997

Acetaminophen absorption test as a marker of small bowel transplant rejection.

We recently evaluated the acetaminophen absorption test as a marker of graft rejection for small bowel transplantation(SBTX). Randomly bred male Wistar rats were used as recipients and donors. Rats (n=45) received heterotopic small intestinal transplants and were divided into three groups (n=15 for each group). In group A, a 10-cm segment of jejunum of was exteriorized as a Thiry-Vella loop. In group B, immunosuppression was not given after SBTX. In group C, rats were treated with FK506 after SBTX (0.3 mg/kg body weight, 0-6 postoperative days). Serum acetaminophen concentrations were measured 15 min after instillation of 0.15 g/kg acetaminophen into the intestinal loop on postoperative days 1, 3, and 7 (n=5 for each group). Blood flow and histology of the graft were also evaluated. In the SBTX group only, the grafts showed the histological change after acute rejection. On day 3, plasma acetaminophen concentrations in this group showed a significant decrease, which correlated with the mild histological changes of graft rejection. Graft blood flow of the SBTX group decreased significantly on day 7, following the severe graft destruction of advanced rejection. No remarkable changes were observed in the other two groups. The acetaminophen absorption test appears to be useful for the early detection of SBTX graft rejection.

Absorption↗
PubMed1997

Metanestin, a glycoprotein with metastasis-associated expression in transitional cell carcinoma of the urinary bladder.

A 60-kDa glycoprotein named metanestin was identified by molecular cloning. The glycoprotein had a twice-repeated motif of Pro-Gly-Pro-Gly and carried metastasis-associated carbohydrate epitopes. The antibody to the protein portion of metanestin strongly reacted with lymph-node metastasis of transitional-cell carcinoma of the urinary bladder, but the reactivity to the primary tumor was generally weaker and the normal urothelium was scarcely reactive. Thus both metanestin and the carbohydrate on it showed metastasis-associated expression. In addition, we identified a 100-kDa glycoprotein with a 4-times-repeated motif of Pro-Ala-Pro-Ala. The antibody to the 100-kDa glycoprotein showed reactivity similar to that to metanestin.

Amino Acid Sequence↗
PubMed1997

Differences in the change in the time course of plasma endothelin-1 and endothelin-3 levels after exercise in humans. The response to exercise of endothelin-3 is more rapid than that of endothelin-1.

Several studies have indicated that endothelin-1 (ET-1) and endothelin-3 (ET-3) are produced by different cells. Although ET-1 is produced by vascular endothelial cells, these cells do not produce ET-3. The presence of ET-3 in the brain of several species suggests that ET-3 is a novel neuropeptide. It is unclear whether there are differences in the release of ET-1 and ET-3 under various physiological conditions in humans. In the present study, we measured the plasma concentrations of both ET-1 and ET-3 before and after endurance exercise on a cycle ergometer. Male athletes exercised on a cycle ergometer for 30 min at intensity of 130% of their individual ventilatory threshold (VT), which is intense exercise. Plasma ET-1 and ET-3 were greatly elevated by exercise, but there was a marked difference in the time-course of the change in plasma concentration between the two peptides. The level of ET-1 peaked 30 min after exercise, whereas that of ET-3 peaked immediately after exercise. Thus, plasma ET-3 increased faster than plasma ET-1 after exercise. The exercise-induced change in the time course in plasma ET-3, but not in ET-1, is similar to that in plasma norepinephrine which is a neurotransmitter, suggesting that the rapid elevation in plasma ET-3 is partly attributable to the neuronal response to exercise. The observed difference in the change in the time course of plasma ET-1 and ET-3 levels suggests that the mechanisms by which exercise alters the release and/or synthesis of these two peptides differ.

Adolescent↗
PubMed1997

Pregnancy increases ET-1-induced contraction and changes receptor subtypes in uterine smooth muscle in humans.

The purpose of the present study was to investigate whether pregnancy affects endothelin (ET)-1-induced contraction, the density ofET receptors, and the ratio of receptor subtypes (ET(A) and ET(B)) in uterine smooth muscle in humans. We also investigated which ET receptor subtypes mediate ET-1-induced contraction in the human uterus. In uterine membrane preparations, (125)I-labeled ET-1 ((125)I-ET-1) binding sites (Bmax) in pregnant women did not differ from those in age-matched nonpregnant women (596.2 +/- 107.1 vs. 512.1 +/- 167.7 fmol/mg protein). The dissociation constant (Kd) in pregnant women did not differ from that in nonpregnant women. Competitive displacement experiments with (125)I-ET-1 binding to the membranes using BQ-123 (ET(A) receptor antagonist) showed that the percentage of ET(A) receptors in uterine muscle was significantly higher in pregnant women than in nonpregnant women (P < 0.01). The calculated ratios of ET(A) to ET(B) receptors in pregnant and nonpregnant uteri were 92:8 and 68:32, respectively. Combination treatment with BQ-788 (ET(B) receptor antagonist) completely inhibited the BQ-123-resistant component of (125)I-ET-1 specific binding. ET-1 caused dose-dependent contractions in isolated human uteri from both pregnant and nonpregnant women. The maximum response was markedly greater in pregnant women than in nonpregnant women, whereas pD2 (-log[EC50]) values did not differ between pregnant and nonpregnant uteri. In pregnant human uterus, BQ-123 (10(-6) M) significantly shifted the dose-dependent curve of ET-1 response to the right, whereas BQ-3020 (ET(B) receptor agonist) did not cause contraction. These results suggested that ET-1-induced contraction of the human uterus is mediated through only ET(A) receptors and that ET-1-induced uterine contraction in humans is markedly increased during pregnancy. In addition, the present study suggests that, although (125)I-ET-1 Bmax are not altered during pregnancy, the proportion of ET(A) receptors is increased and that of ET(B) receptors is decreased in the pregnant human uterus.

Adult↗
PubMed1997

Does endothelin-1 participate in the exercise-induced changes of blood flow distribution of muscles in humans?

Endothelin-1 (ET-1) is an endothelium-derived potent vasoconstrictor peptide that potentiates contractions to norepinephrine in human vessels. We previously reported that the circulating plasma concentration of ET-1 is significantly increased after exercise (S. Maeda, T. Miyauchi, K. Goto, and M. Matsuda. J. Appl. Physiol. 77: 1399-1402, 1994). To study the roles of ET-1 during and after exercise, we investigated whether endurance exercise affects the production of ET-1 in the circulation of working muscles and nonworking muscles. Male athletes performed one-leg cycle ergometer exercise of 30-min duration at intensity of 110% of their individual ventilatory threshold. Plasma concentrations of ET-1 in both sides of femoral veins (veins in the working leg and nonworking leg) and in the femoral artery (artery in the nonworking leg) were measured before and after exercise. The plasma ET-1 concentration in the femoral vein in the nonworking leg was significantly increased after exercise, whereas that in femoral vein in the working leg was not changed. The arteriovenous difference in ET-1 concentration was significantly increased after exercise in the circulation of the nonworking leg but not of the working leg, which suggests that the production of ET-1 was increased in the circulation of the nonworking leg by exercise. The present study also demonstrated that the plasma norepinephrine concentrations were elevated by exercise in the femoral veins of both the working and nonworking legs, suggesting that the sympathetic nerve activity was augmented in both legs during exercise. Therefore, the present study demonstrates the possibility that the increase in production of ET-1 in nonworking muscles may cause vasoconstriction and hence decrease blood flow in nonworking muscles through its direct vasoconstrictive action or through an indirect effect of ET-1 to enhance vasoconstrictions to norepinephrine and that these responses may be helpful in increasing blood flow in working muscles. We propose that endogenous ET-1 contributes to the exercise-induced redistribution of blood flow in muscles.

Adolescent↗
PubMed1997

Multiple brain gas embolism after ingestion of concentrated hydrogen peroxide.

We present a 63-year-old man who developed multiple brain infarction after ingesting a 35% hydrogen peroxide solution. Neurologic examination revealed left hemiparesis, primarily affecting the lower limb, and mild weakness of the right lower limb. Gadolinium-enhanced MRI revealed patchy bilateral brain lesions. Oxygen gas embolization is the likely cause of the brain infarctions.

Accidents↗
PubMed1996

Inhibition of myocardial endothelin pathway improves long-term survival in heart failure.

Occlusion of the diseased coronary artery in humans causes acute myocardial infarction, survivors of which have a high risk for the development of chronic heart failure. Cardiac myocytes and vascular endothelial cells produce endothelin-1 (refs 2-4), which increases the contractility of cardiac muscle and of vascular smooth muscle cells. Endothelin-1 also exerts long-term effects such as myocardial hypertrophy, and causes cellular injury in cardiac myocytes. Production of endothelin-1 is markedly increased in the myocardium of rats with heart failure, and acute application of an endothelin-receptor antagonist decreases myocardial contractility in such rats, indicating that myocardial endothelin-1 may help to support contractility of the failing heart. But we report here that the upregulated myocardial endothelin system may contribute to the progression of chronic heart failure, because long-term treatment with an endothelin-receptor antagonist greatly improved the survival of rats with chronic heart failure. This beneficial effect was accompanied by significant amelioration of left ventricular dysfunction and prevention of ventricular remodelling, in which there is usually an increase in the ventricular mass and cavity enlargement of the ventricle.

Animals↗
PubMed1996

Pulmonary hypertension caused by congestive heart failure is ameliorated by long-term application of an endothelin receptor antagonist. Increased expression of endothelin-1 messenger ribonucleic acid and endothelin-1-like immunoreactivity in the lung in congestive heart failure in rats.

OBJECTIVES: The purpose of this study was to investigate whether 1) endothelin-1, a potent vasoconstrictor peptide, is involved in progression of pulmonary hypertension caused by congestive heart failure (CHF); and 2) whether long-term treatment with BQ-123, an endothelin receptor antagonist, ameliorates pulmonary hypertension caused by CHF. BACKGROUND: Congestive heart failure accompanies pulmonary hypertension, and the severity of pulmonary hypertension is an important determinant of prognosis. Although we reported that production of endothelin-1 is increased in the failing heart in rats with CHF, it is not known whether production of endothelin-1 in the lung is altered by CHF. METHODS: Congestive heart failure was induced by coronary artery ligation in rats. Expression of preproendothelin-1 messenger ribonucleic acid (mRNA) in the lung and kidney was determined. Endothelin-1 staining (immunoreactivity) in the lung was studied by immunohistochemical analysis. Effects of long-term BQ-123 treatment on the rats were studied. RESULTS: Two weeks postoperatively, CHF accompanied by pulmonary hypertension developed in the rats (CHF rats). Expression of preproendothelin-1 mRNA in the lung was markedly higher in the CHF rats than in the sham-operated rats, whereas that in the kidney did not differ between the two groups. Endothelin-1 staining on the pulmonary vascular endothelial cells was more intense in the CHF rats. BQ-123 treatment over a 2-week period in the CHF rats greatly reduced right ventricular systolic pressure and central venous pressure, but it did not affect blood pressure or left ventricular contractility (peak positive first derivative of left ventricular pressure) in these rats. CONCLUSIONS: Long-term BQ-123 treatment greatly ameliorated pulmonary hypertension in the CHF rats. The present study suggests that endothelin-1 plays an important role in the progression of pulmonary hypertension caused by CHF and that an endothelin receptor antagonist may be a new therapeutic agent for CHF-induced pulmonary hypertension.

Animals↗
PubMed1996

Roles of basigin, a member of the immunoglobulin superfamily, in behavior as to an irritating odor, lymphocyte response, and blood-brain barrier.

Basigin is a transmembrane glycoprotein belonging to the immunoglobulin superfamily. Using the knockout mouse lacking the basigin gene (Bsg), we analyzed the function of basigin in adult mice lacking the gene [Bsg (-1-)]. Although histochemical studies on the localization of basigin (also called HT7 and neurothelin) strongly indicated that it is involved in the function of the blood-brain barrier, basigin knockout mice showed only a little difference, if any, to wild-type mice in the function of the blood brain-barrier. The mitogenic response of lymphocytes upon mixed lymphocyte reaction was greater in Bsg (-1-) mice. Finally, Bsg (-1-) mice repeatedly visited filter paper impregnated with acetic acid or isozine, indicating an abnormality in either reception of the odor or behavior as to it.

Animals↗