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Biomedical subjects

Y Kumahara

Publications and source records attributed to Y Kumahara.

At least 19 recordsLinked to original sources
PubMed1992

Clinical and basic aspects of an anorexiant, mazindol, as an antiobesity agent in Japan.

The Japanese Mazindol study group investigated the action of an anorexiant, mazindol, and found that it reduced food intake by directly suppressing neurons in the lateral hypothalamus, inhibited gastric acid secretion, increased motor activity, decreased glucose absorption, and inhibited insulin secretion. It thus appears that the main effect of mazindol is to decrease food intake through suppressing feeding centers in the hypothalamus. A multicenter open study of mazindol in Japan revealed that loss of body weight and relative body weight in 14 wk were 4.6 kg and 9.2%, respectively, with suppression of appetite in the majority of obese patients. A multicenter double-blind study demonstrated that mazindol was superior to the placebo in the treatment of simple obesity. We also suggest that mazindol is effective in the maintenance of reduced body weight after obesity therapy and in the treatment of obesity-related diseases such as diabetes, hypertension, or hyperlipidemia.

Animals↗
PubMed1992

Analysis of the apolipoprotein B3' hypervariable region in patients with essential hypertension.

1. The typing of the apolipoprotein B 3' hypervariable region was investigated in hypertensive and normotensive subjects using rapid typing of a variable number of tandemly repeated short DNA sequences (VNTR) by the polymerase chain reaction. 2. In the DNA samples of 89 normotensive and 99 hypertensive patients, 13 different-sized alleles were detected. The most frequent allele has 35 repeat units in both groups with frequencies of 0.624 and 0.596 in normotensive and hypertensive patients, respectively. Frequency distribution of 13 alleles was similar in both groups. 3. These results demonstrate no association between the apolipoprotein B gene polymorphism and essential hypertension.

Aged↗
PubMed1991

Clinical evaluation of delapril in Japan. Report from the Japan Study Group on Delapril.

Delapril, a new angiotensin converting enzyme (ACE) inhibitor discovered in the laboratory of Takeda Chemical Industries, Ltd., is the result of drug design based on the structure-activity relationships of ACE inhibitors. Delapril is an antihypertensive agent with a relatively long duration of action and no SH moiety in its structure. Following administration, it is converted into two active metabolites. Delapril effectively lowered blood pressure in 73% of 1,008 patients with hypertension during clinical trials in Japan. Efficacy rates were 73% for essential hypertension, 85% for renal hypertension, and 80% for renovascular hypertension. Excellent hypotensive response was observed in all age groups, from young to elderly patients. Side effects during administration of delapril, based on subjective evidence, were reported in 80 out of the 1,008 cases (7.9%). The main symptoms included orthostatic dizziness (1.7%), dizziness (1.3%), and nausea (1.1%). Dry cough, which has attracted attention in recent years as a side effect of ACE inhibitors, was reported at a low incidence of 1.1%. In a double-blind, controlled study in patients with mild to moderate essential hypertension in which captopril served as a positive control, delapril showed superior hypotensive effect and greater safety. Data derived from the Japan Study Group on Delapril indicate that this ACE inhibitor has excellent hypotensive effects and a high level of safety. It is suitable as a first-line drug in both monotherapy and combined therapy.

Adolescent↗
PubMed1990

Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients.

The frequency of spontaneous 6-thioguanine (TG)-resistant peripheral blood lymphocytes in five unrelated Werner syndrome (WS) patients was determined using an autoradiographic labeling assay. The average frequency of TG-resistant lymphocytes was eightfold higher in WS patients than in sex- and age-matched normal control donors. This finding and previous identification of increased spontaneous chromosomal rearrangements and deletions in WS cells or cell lines suggest that WS is a human genomic instability or mutator syndrome.

Adult↗
PubMed1990

[Calcitonin].

Explore the source record for details and available documents.

Adenylyl Cyclases↗
PubMed1989

Effects of very-low-calorie diet weight reduction on glucose tolerance, insulin secretion, and insulin resistance in obese non-insulin-dependent diabetics.

We put 12 obese subjects on a very-low-calorie diet (VLCD) and observed how their weight loss affected their glucose tolerance. Seven had non-insulin-dependent diabetes and five did not. They consumed 1000 kcal/day for at least 1 week, then 420 kcal/day for 4 weeks, and 1000 kcal/day thereafter. VLCD improved glucose tolerance and insulin response to a glucose load in the diabetics and did not affect these parameters in the non-diabetics. It did not change insulin responsiveness to intravenous glucagon in either group. Both groups showed improved insulin resistance, as measured by an insulin suppression test. Regression analysis showed that insulin resistance correlates well with obesity and glycemic control. Weight reduction did not change hepatic insulin extraction. Thus, the improvement in glucose tolerance by some of the diabetics seems to have arisen from improvements in their insulin resistance and insulin response to a glucose load. Insulin resistance improved because of weight reduction and subsequent improvements in glycemic control.

Adult↗
PubMed1989

Effects of the kallikrein-kinin system on phasic coronary vasospasm in dogs.

It is well known that kinins are liberated from kininogen in blood during angina attack to maintain blood flow in coronary artery. We examined the effects of bradykinin, one of kinins, on the coronary artery other than vasodilation. The isolated canine coronary artery ring was suspended in gassed (95% O2, 5% CO2) Krebs-Henseleit buffer at 37 degrees C in vitro. The experimental phasic contraction of coronary artery was induced by 6 x 10(-4)M of 3,4-diaminopyridine which decreases K conductance (Y. Uchida, Jpn. Circ. J: 49, 128, 1985). The effect of bradykinin and other substances on the cycle length of contraction (CL), the peak tension of contraction phase (PT) and the tension during relaxation phase (RT) were observed. The phasic contraction was eliminated by 10(-7)M nifedipine and 10(-6)M diltiazem which block voltage dependent Ca channels. These Ca blockers reduced PT, but slightly increased CL, and weakly reduced RT. The phasic contraction was also eliminated by 10(-6)M bradykinin. However, bradykinin, unlike Ca blockers, did not reduce PT, but markedly prolonged CL and decreased RT significantly. This inhibition mode was very similar to those of nicorandil which increases K conductance. These data suggest that bradykinin plays a protective role in coronary vasospasm, and this antivasospasm effect may be mediated through the increase in K conductance.

Animals↗
PubMed1989

Remarkable effect of endocrine therapy on brain metastasis from prostatic carcinoma.

The brain metastasis of prostatic carcinoma is rare and is distinguished by its poor prognosis in cases which are not surgically resectable. Herein we report on a case of brain metastasis of prostatic carcinoma which showed a dramatic regression through bilateral orchiectomy and doses of diethylstilbestrol diphosphate and estramustine phosphate. Neurologic and psychiatric symptoms diminished within three months, and the patient is alive and well without any subjective symptoms after twelve months.

Adenocarcinoma↗
PubMed1989

Renal interaction of atrial natriuretic peptide with angiotensin II: glomerular and tubular effects.

1. The possible interactions between the renal effects of atrial natriuretic peptide (ANP) and angiotensin II (AII) were studied in normal sodium-replete human subjects. Recent investigations have suggested that ANP inhibits the pressor and volume-retaining effects of activation of the renin-angiotensin system. Thus, ANP may attenuate the effects of AII on renal haemodynamics or tubular transport. 2. ANP (0.1 micrograms/kg per min, 60 min) was intravenously infused into eight normal human subjects with and without pretreatment with enalapril (20 mg, per oral), an inhibitor of the converting enzyme, and during infusion of AII (10 mg/kg per min). 3. ANP infusion alone caused increases in the urine volume (from 96 +/- 23 to 229 +/- 44 mL/h, P less than 0.05) and urinary sodium excretion (from 11.5 +/- 1.6 to 20.9 +/- 4.2 mEq/h, P less than 0.05). These changes were accompanied by an increase in the glomerular filtration rate (from 127 +/- 9 to 158 +/- 9 mL/min, P less than 0.05). ANP infusion after enalapril administration lowered the mean blood pressure (from 76 +/- 2 to 71 +/- 3 mmHg, P less than 0.05) to a level similar to that observed during ANP infusion alone (from 84 +/- 2 to 74 +/- 2 mmHg, P less than 0.01), but did not result in a significant diuresis (from 139 +/- 23 to 174 +/- 51 mL/h) or natriuresis (from 19.7 +/- 2.5 to 14.3 +/- 3.4 mEq/h, P less than 0.05). This combined treatment with a converting enzyme inhibitor and ANP reduced both the glomerular filtration rate (160 +/- 9 to 141 +/- 10 mL/min) and the renal plasma flow (from 775 +/- 49 to 570 +/- 45 mL/min, P less than 0.01). 4. The antinatriuretic effects of exogenous AII were reversed by superimposed ANP infusion (urinary sodium excretion: from 4.8 +/- 1.0 to 24.3 +/- 5.2 mEq/h, P less than 0.01). Under these conditions, the glomerular filtration rate increased (from 114 +/- 6 to 156 +/- 7 mL/min, P less than 0.05) to levels similar to those observed with ANP infusion alone. In addition the increased tubular sodium reabsorption induced by AII was inhibited by concomitant ANP infusion (fractional proximal tubular sodium reabsorption: from 90.7 +/- 3.5 to 80.3 +/- 16.6%, P less than 0.05, fractional post-proximal tubular sodium reabsorption: from 91.5 +/- 9.8 to 87.6 +/- 8.8%, P less than 0.05).(ABSTRACT TRUNCATED AT 400 WORDS)

Adult↗
PubMed1989

Synergism of intraventricular NaCl infusion and subpressor angiotensins in rats.

The effect of selective salt infusion to the central nervous system on the blood pressure (BP) regulation was examined in male Wistar rats. Hypertonic NaCl (0.8 M, 1 microliter/h) was infused into the lateral ventricle concomitantly with intravenous infusion of a subpressor dose (5.4 pmol.kg-1.min-1) of angiotensin II (ANG II) or its analogues for 7 days using osmotic minipumps. The BP was not increased by intracerebroventricular infusion of NaCl alone at this dose but was significantly and consistently increased by concomitant intravenous infusion of ANG II or its analogues. The increases in the BP over the base-line values on day 7 in groups on infusions of ANG II, ANG III, and pentasarcosyl-ANG II [(Sar)5ANG II] were 29 +/- 5 mmHg (n = 9, P less than 0.05), 8 +/- 2 mmHg (n = 8, P less than 0.05), and 19 +/- 3 mmHg (n = 6, P less than 0.05), respectively. The responses to hexamethonium, prazosin, and antagonists of arginine vasopressin and ANG II were examined in separate sets of conscious and unrestrained animals that had received intracerebroventricular infusion of NaCl and intravenous infusion of ANG II for the preceding 6 days. These animals showed significantly greater depressor responses only to hexamethonium and prazosin than control. These results indicate that the pressor effect of continuous and concomitant administration of intracerebroventricular NaCl and intravenous ANG II is mainly due to activation of the sympathetic nerve function. Synergism of the effects of selective central sodium administration and a subpressor dose of ANG II in the central nervous system is suggested.

Angiotensins↗
PubMed1989

Renin inhibitor and converting enzyme inhibitors suppress vascular angiotensin II.

The direct effects of a renin inhibitor, N-acetyl-pepstatin and five angiotensin converting enzyme inhibitors, captopril and the active diacid forms of enalapril, ramipril, cilazapril, and CS-622, on the vascular renin-angiotensin system were examined in isolated perfused rat mesenteric arteries. Vascular renin activity and angiotensin II (Ang II) released into the perfusate were determined. Infusion of N-acetyl-pepstatin (5 X 10(-8)-5 X 10(-6) M) suppressed vascular renin activity and Ang II release dose dependently. Isoproterenol (10(-6) M) induced a 135 +/- 30% increase in Ang II release from the basal value. N-Acetyl-pepstatin (5 X 10(-6) M) suppressed isoproterenol-induced Ang II release. Infusions of 5 X 10(-6) M captopril and the diacid forms of enalapril, ramipril, cilazapril, and CS-622 by themselves had little effect on Ang II release, but concomitant infusion of isoproterenol with these angiotensin converting enzyme inhibitors significantly decreased Ang II release (71 +/- 21%, 51 +/- 40%, 8 +/- 21%, 69 +/- 24%, and 44 +/- 29% increase, respectively, from the basal values). These results indicate that N-acetyl-pepstatin suppresses the vascular renin-angiotensin system. This effect may in part contribute to the hypotensive actions of renin inhibitors. Although angiotensin converting enzyme inhibitors also suppress locally generated Ang II, the mechanism and physiological significance still remain to be clarified.

Angiotensin II↗
PubMed1989

Contribution of the baroreflex afferent nerves to the production of vasoconstricted hypertension in volume-expanded dogs.

Dextran in lactated Ringer's solution (20 ml/kg) was infused for 1 hour into anesthetized dogs with sinoaortic denervation and vagotomy (deafferentation; n = 10) and dogs treated with hexamethonium (de-efferentation; n = 13) to compare with our previous observation in dogs with an intact autonomic nervous system (control, n = 34). During the infusion, increase in blood pressure associated with increase in cardiac output was observed in all three groups. The increases in blood pressure were larger in the two groups with an impaired autonomic nervous system. In the recovery period, the control dogs and the hexamethonium-treated dogs showed gradual increases in total peripheral resistance and in vasoconstricted hypertension 3 hours after stopping the infusion. In contrast, the dogs with sinoaortic denervation and vagotomy did not show any increase in total peripheral resistance. The vasoconstricted groups showed peaks of natriuresis soon after the infusion, not 3 hours after the infusion when vasoconstriction was observed, although the dogs with deafferentation did not show a significant increase in natriuresis. Norepinephrine (0.5 micrograms/kg) was administered intravenously before and after volume expansion, and the pressor responses in the three groups after volume expansion were enhanced similarly (143%, 128%, and 136%, respectively). These results indicate that the afferent signals from peripheral vessels to the brain contribute to the production of vasoconstricted hypertension after acute volume expansion and that the vasoconstriction is independent of pressor hypersensitivity and is dissociated in time from the natriuresis.

Afferent Pathways↗
PubMed1989

Effect of atrial natriuretic peptide on catecholamine release from human pheochromocytoma.

The effect of synthetic alpha human atrial natriuretic peptide on catecholamine release from human pheochromocytomas was studied both in vivo and in vitro. Iv infusion of atrial natriuretic peptide at a rate of 0.1 microgram.kg-1.min-1 for 60 min into two normotensive patients with pheochromocytoma caused a small decrease in the mean blood pressure, increase in the heart rate, and marked increase in the plasma level of norepinephrine (2.08 to 6.83 nmol/l, and 1.15 to 2.83 nmol/l, respectively) compared with 0.60 +/- 0.10 to 1.19 +/- 0.20 nmol/l in normal subjects. Treatment with atrial natriuretic peptide also increased the plasma epinephrine level from 0.34 to 1.27 nmol/l, and from 0.67 to 0.79 nmol/l in the patients with pheochromocytoma, but not in the normal subjects (0.05 +/- 0.01 to 0.05 +/- 0.01 nmol/l). After removal of the tumour, the responses of the plasma norepinephrine and epinephrine to atrial natriuretic peptide infusion were normalized. There was no significant effect of 10(-8) to 10(-5) mol/l atrial natriuretic peptide on the basal release of catecholamines from isolated superfused pheochromocytoma tissue. Atrial natriuretic peptide (10(-7) mol/l) did not affect the increase in catecholamine release induced by glucagon (10(-5) mol/l). These results suggest that the exaggerated responses of plasma catecholamines to atrial natriuretic peptide in patients with pheochromocytoma may be due to a washout effect resulting from change in blood flow in the vessels feeding the tumour rather than increased sympathetic nerve activity induced by hypotension and hypovolemia. The results also suggest that atrial natriuretic peptide dose not have any direct action on pheochromocytoma tissue causing catecholamine release.

Adrenal Gland Neoplasms↗
PubMed1989

Role of angiotensin II in the renal response to atrial natriuretic peptide in normal subjects.

Atrial natriuretic peptide (ANP) has been shown to inhibit angiotensin II (Ang II)-induced steroidogenesis and vasoconstriction. To investigate the role of Ang II in the renal response to ANP, a synthetic ANP (0.1 micron/kg/min, 60 min) was infused for 1 h in eight subjects with or without pretreatment with an inhibitor of the converting enzyme, enalapril (20 mg, p.o.), or Ang II (10 ng/kg/min). ANP infusion alone caused increases in urinary volume, urinary sodium excretion, and glomerular filtration rate (GFR). However, enalapril treatment abolished these diuretic and natriuretic effects of ANP. In this group, GFR was decreased and no tubular effects, which was estimated by urinary excretion of sodium and phosphate, were observed. The anti-natriuretic effects of exogenous Ang II were reversed by concomitant ANP infusion, which inhibited both proximal and postproximal sodium reabsorption induced by Ang II without changing the GFR. These results indicate that endogenous Ang II plays an obligatory role in the natriuretic response to ANP and also suggested that ANP inhibits Ang II-stimulated tubular reabsorption of sodium.

Adult↗
PubMed1989

Tubular dysfunction in the early stage of diabetic nephropathy.

Renal tubular function was investigated in 98 non-insulin-dependent and 18 insulin-dependent diabetics under conditions of standard glycemic control. Mean urinary excretion of lysozyme, beta 2-microglobulin and N-acetyl-beta-D-glucosaminidase (NAG) in both Albustix-negative and positive patients were significantly elevated above the control range. The increased excretion of lysozyme, beta 2-microglobulin and NAG was found in 21, 55 and 62% of the normoalbuminuric patients, and in 40, 57 and 74% of the microalbuminuric patients, respectively. Besides the parameters cited above, urinary acid-soluble glycoprotein (ASP) was measured to assess its potential as an indicator of early renal dysfunction. Mean urinary ASP excretion was also elevated in both Albustix-negative and positive patients. The albumin/ASP ratio increased as nephropathy advanced. Such a mode of excretion was similar to those of low-molecular-weight proteins (lysozyme and beta 2-microglobulin). The results of multiple regression analysis showed that serum creatinine most highly correlated with the excretion of the urinary proteins except for NAG.

Acetylglucosaminidase↗