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Biomedical subjects

K Kaku

Publications and source records attributed to K Kaku.

At least 127 records · Page 7Linked to original sources

Effect of tolbutamide on fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase in rat liver.

The effects of tolbutamide on the activities of fructose-6-phosphate,2-kinase and fructose-2,6-bisphosphatase were examined using rat hepatocytes. Tolbutamide stimulated fructose-6-phosphate,2-kinase activity and inhibited fructose-2,6-bisphosphatase activity, resulting in an increase of fructose-2,6-bisphosphate level. Changes in the activities of the enzyme by tolbutamide were due to variation in the Km value, but not dependent on alteration of Vmax. Glucagon inhibition of fructose-2,6-bisphosphate formation resulting from an inactivation of fructose-6-phosphate,2-kinase and an activation of fructose-2,6-bisphosphatase was released by tolbutamide. Tolbutamide stimulation of fructose-2,6-bisphosphate formation through regulation of fructose-6-phosphate,2-kinase/fructose-2,6-bisphosphatase may produce enhancement of glycolysis and inhibition of gluconeogenesis in the liver.

Animals↗

Circadian cycles in VIP content and VIP stimulation of cyclic AMP accumulation in the rat pineal gland.

VIP content in the rat pineal gland and cyclic AMP accumulation in response to VIP in the daily light and dark cycle were examined. VIP content in the pineal varied significantly during the day and night; the content decreased during exposure to light and was lowest at the onset of darkness, 6 p.m. (mean +/- SE, 23 +/- 5 pg/pineal), and increased during the night and was highest at the onset of light, 6 a.m. (72 +/- 12 pg/pineal). Response of cyclic AMP accumulation to VIP varied with a periodicity inversely related to the daily light and dark cycle of VIP content; cyclic AMP accumulation in response to 10(-7) M VIP increased in proportion to periods of exposure to light and peaked at 6 p.m., and decreased with the onset of darkness.

Animals↗

Effects of intravenous injection of isosorbide dinitrate on the cardiovascular system.

An assessment of the acute hemodynamic effect of intravenous isosorbide dinitrate (ISDN) was performed with a Mikro-tip angiocatheter in 10 patients during the diagnostic cardiac catheterization. Both left ventricular (LV) systolic pressure (SP) and end-diastolic pressure (EDP) were decreased by 2 mg of ISDN. Cardiac index, stroke work index and heart rate did not change significantly, and neither systemic vascular resistance nor pulmonary arteriolar resistance was reduced. Isovolumic phase and ejection phase indices of contractility were not altered. End-diastolic stress, an accurate index of preload, was reduced significantly (47.0 +/- 27.6 to 28.7 +/- 24.6 g/cm2, p less than 0.01), and mid-systolic stress, an index of afterload, was also reduced (371 +/- 102 to 332 +/- 85 g/cm2, p less than 0.05). No undesirable side effects were noted during this study. We concluded that bolus intravenous (IV) ISDN safely reduced both preload and afterload. As 2 mg of IV ISDN had no significant change on SVR, a larger dose of ISDN bolus injection might be needed for a significant arterial vasodilating effect. Bolus IV ISDN seems to be very effective in cases in which rapid reduction of LV filling pressure is mandatory.

Adult↗

Regulation of muscle fructose 2, 6-bisphosphate levels by sulfonylureas.

We examined the effect of sulfonylureas on the level of fructose 2, 6-bisphosphate (F-2, 6-P2) in muscle using a mouse hindlimb flow-through perfusion system. The F-2, 6-P2 level in muscle was increased by adding glibenclamide or tolbutamide in a dose-dependent manner. The stimulatory potency of each drug on F-2, 6-P2 formation was parallel to its hypoglycemic potency. Sulfonylurea stimulation of muscle F-2, 6-P2 formation is thought to be an important extrapancreatic action improving the deranged carbohydrate metabolism in diabetics.

Animals↗

[Four cases of male breast cancer including one synchronously combined with gastric cancer].

Four men with primary breast cancer were seen between 1972 and 1985 at the Sasebo Municipal Hospital. They were admitted complaining of breast mass and/or bloody nipple discharge. There was no delay between the onset of symptoms and seeking medical advice. They had relatively early stages of disease (three patients had stage I and one had stage II). All patients were treated by modified radical or radical mastectomy. Histopathological study revealed ductal carcinomas and no lymph node metastasis in all patients. Multiple bone metastasis and death occurred in one case. One patient (61 years old) had two separate synchronous primary cancers of the breast and stomach, which is very uncommon.

Adenocarcinoma, Papillary↗

Sulfonylurea stimulates liver fructose-2,6-bisphosphate formation in proportion to its hypoglycemic action.

The effects of 5 sulfonylureas on fructose-2,6-bisphosphate (F-2,6-P2) formation using isolated perfused rat liver were examined. All sulfonylureas examined stimulated dose-dependent formation of the activator in a limited range of the concentration. A maximum effect on F-2,6-P2 formation was observed at the concentration of 10(-3) M of tolbutamide or chlorpropamide, at 10(-4) M of gliclazide or acetohexamide and at 10(-6) M of glibenclamide. These concentrations of sulfonylurea correspond with those in blood when therapeutical doses of the drug are administered orally. Sulfonamide and biguanide did not show any stimulatory effect on F-2,6-P2 level. The results demonstrate that stimulation of liver F-2,6-P2 formation is a common characteristic of sulfonylureas and suggest strongly that one of the extrapancreatic actions of sulfonylurea is stimulation of F-2,6-P2 formation followed by enhancement of glycolysis and inhibition of gluconeogenesis in the liver.

Acetohexamide↗

Vasoactive intestinal peptide binding to specific receptors on rat parotid acinar cells induces amylase secretion accompanied by intracellular accumulation of cyclic adenosine 3'-5'-monophosphate.

Specific binding sites for vasoactive intestinal polypeptide (VIP) were characterized in dispersed rat parotid acini. The binding of [125I]VIP was rapid, saturable, reversible, and temperature dependent. Scatchard analysis indicated two functionally independent classes of receptor sites: 41,000 high affinity-low capacity sites per cell with a dissociation constant (Kd) of 6.4 nM and 420,000 low affinity-high capacity sites per cell with a Kd of 150 nM. A peptide with N-terminal histidine and C-terminal isoleucine and secretin, which are structurally related to VIP, inhibited the tracer binding 30 and 200 times less strongly, respectively, than VIP. Epinephrine and carbachol did not inhibit [125I]VIP binding to parotid acinar cells. VIP stimulated cAMP accumulation in parotid lobules and induced amylase secretion in a dose-dependent manner. A peptide with N-terminal histidine and C-terminal isoleucine and secretin were less potent than VIP regarding cAMP accumulation (1/12 and 1/80 of VIP, respectively) and amylase secretion (1/40 and 1/500 of VIP, respectively). Substance P did not stimulate cAMP accumulation but stimulated amylase secretion more strongly than VIP. These observations clearly demonstrated the presence of VIP receptors coupled to adenylate cyclase system in the rat parotid gland, which plays an important role in the regulation of the amylase secretion. The regulation of parotid function by VIP was independent of the adrenergic or muscarinic regulatory system and of the influence of substance P.

Amylases↗

Light and agonist alter vasoactive intestinal peptide binding and intracellular accumulation of adenosine 3',5'-monophosphate in the rat pineal gland.

We examined the effects of environmental light and prior treatment with an agonist on vasoactive intestinal polypeptide (VIP) binding and VIP stimulation of cAMP accumulation in the rat pineal gland. VIP binding to pinealocytes and cAMP accumulation in response to VIP were significantly increased in animals kept exposed to constant light compared to those in animals experiencing a dark night before the experiments. Scatchard analysis of [125I]VIP binding indicated the presence of two classes of binding sites: high affinity, low capacity sites and low affinity, high capacity sites. The increased VIP binding to pinealocytes in rats maintained in constant light was attributed to an increase in the number of available VIP receptors at both high and low affinity sites. The affinity of VIP binding to cells was not affected by exposure of the animals to light. VIP stimulation of cAMP accumulation was not inhibited by d,l-propranolol. Prior treatment of pinealocytes with VIP decreased [125I]VIP binding by reducing the number of receptors and significantly inhibited subsequent VIP stimulation of cAMP accumulation. Prior treatment with norepinephrine did not alter the number of VIP receptors. Our results strongly suggest that VIP is a neuromodulator of pineal function.

Animals↗

Study on the mitral valve prolapse. I. Incidence in Kobe University students. II. Follow up study.

Incidence of mitral valve prolapse (MVP) in 4517 students of Kobe University, and clinical features in cases with MVP were studied. MVP was detected in 42 cases by two-dimensional echocardiography, and the prevalence of MVP was 0.93 percent (42 of 4517 cases). Among 42 cases with MVP, apparent mitral regurgitation (MR) was noted in one case with severe MVP, ventricular tachycardia was detected in one and ST-T wave abnormalities were detected in 10 respectively. In another follow up study of our hospital, 14 of 85 patients followed more than one year were noted to be deterioration in echocardiographic parameters. Eight of 14 patients had severe prolapse with severe MR, but remaining 6 had mild or moderate prolapse with mild or absent of MR. However, ST-T wave abnormalities, serious arrhythmias, and low response of %FS increase on exercise were found in high incidence in 6 of mild or moderate prolapse as well as in severe prolapse. So these follow up results suggested that not only students with severe MVP but also students with mild or moderate MVP with ST-T wave changes or VPC found in university medical examination must be followed up carefully.

Adolescent↗

Effects of bombesin and gastrin releasing peptide on catecholamine secretion from rat adrenal gland, in vitro.

The effects of bombesin and gastrin releasing peptide (GRP) on the release of catecholamine were investigated by using isolated rat adrenal gland. Bombesin and GRP stimulated an epinephrine (E) release with dose-dependency. A half maximal effect of bombesin was observed at 1.2 X 10(-9) M, and a maximal release of E occurred at 1 X 10(-6) M of bombesin. The stimulatory effect of GRP on the E release was very similar to that of bombesin. Although both these peptides also stimulated a norepinephrine (NE) release, a significant effect was detected at concentrations of bombesin and GRP above 1 X 10(-7) M. Nicotine and pilocarpine stimulated both E and NE releases dose dependently, but the effect of pilocarpine on E and NE release was 1/100 or less potent than that of nicotine. Bombesin-induced catecholamine releases were not inhibited by hexamethonium or atropine that fully impeded the stimulatory effects of nicotine or pilocarpine. In addition, bombesin had additive effects on the nicotine- or pilocarpine-induced E and NE releases. These data strongly suggest that bombesin or GRP plays a physiological role as one of the important regulators in catecholamine secretion in the adrenal gland.

Adrenal Glands↗

[Hypertrophic cardiomyopathy with progressive left ventricular hypertrophy: a case report].

A 64-year-old man was hospitalized in March 1983 for recurrent episodes of dyspnea and palpitation despite medical treatment. At 48 years of age (1967), hypertension was diagnosed, but well controlled by propranolol. At the age of 59 years (1979), his first episode of dyspnea and palpitation was noted, with electrocardiographic (ECG) evidence of left ventricular hypertrophy (LVH), and abnormal Q waves in leads III and a VF. The echocardiogram, however, showed mild LVH with neither asymmetric septal hypertrophy (ASH) nor systolic anterior movement (SAM). On admission (1983), his blood pressure was 130/70 mmHg, and a grade III systolic murmur was heard along the left sternal border and over the apex. On ECG, the left precordial voltage (Sv1 + Rv5) was diminished and the depth of the Q wave in lead III increased compared with that of 1978. On echocardiography, we observed prominent septal hypertrophy (IVST: 20 mm) with ASH (IVST/PWT = 2.0), SAM, an enlarged left atrium, and a diminished left ventricular (LV) cavity. Left ventricular catheterization showed a pressure gradient of 90 mmHg between the LV apex and outflow tract and histological examination of the bi-ventricular endomyocardial biopsy material showed markedly hypertrophied and mildly disarranged myocardial fibers with bizarre nuclei. We considered that this was an interesting case in which ASH and SAM developed in the progression of LVH during the follow-up period.

Cardiac Catheterization↗

[Regional right ventricular hypertrophy in hypertrophic cardiomyopathy and hypertension].

The mode of right ventricular hypertrophy was assessed by two-dimensional echocardiography (2DE) for 24 patients with hypertrophic cardiomyopathy (HCM), and the results were compared with those of 51 patients with hypertension (HT). The patients with HT were categorized in four groups depending on the thickness of the interventricular septum (IVST) and left ventricular posterior wall (PWT): HT-ASH with both left ventricular hypertrophy (LVH) (IVST greater than or equal to 13 mm) and asymmetric septal hypertrophy (ASH) (IVST/PWT greater than or equal to 1.3), severe HT with LVH and without ASH, and mild HT without LVH and ASH. Anterior wall thickness (AWT), posterior wall thickness (PWT), and diaphragmatic wall thickness (DWT) of the right ventricle were obtained from 2DE in the parasternal long-axis view, the short-axis view and subxiphoid view, respectively. These were recorded on video tape, and the measurements were made on the stop frames. Right ventricular hypertrophy (RVH) was estimated by the maximal right ventricular wall thickness (max RVWT), and the ratio of the maximal and minimal thickness (max RVWT/min RVWT) was calculated to evaluate asymmetrical hypertrophy (AH) of the right ventricle (RV). The incidence of RVH (Max RVWT greater than or equal to 5 mm) and asymmetrical hypertrophy (AH) (max RVWT/min RVWT greater than or equal to 1.3) of the RV in HCM, HT-ASH and mild HT were 67% and 41%, 57% and 45%, and 15% and 11%, respectively. The incidence of RVH with AH was more frequent in patients with HCM as well as HT with ASH than in patients with HT without ASH.(ABSTRACT TRUNCATED AT 250 WORDS)

Cardiac Volume↗

Mechanisms of compensation and decompensation in dilated cardiomyopathy.

Left ventricular (LV) function was evaluated in 32 patients with dilated cardiomyopathy (DC) who underwent cardiac catheterization during the past 6 years (group 4), and the results were compared with the data of 30 normal subjects (group 1). The patients were divided into mildly (group 2, 12 patients) and severely symptomatic subgroups (group 3, 20 patients). DC was characterized by dilated and poorly contracting left ventricle with increased muscle mass, reduced cardiac output and elevated systemic vascular resistance. LV volume was larger, ejection fraction was lower, and end-diastolic and end-systolic stresses were higher in group 3 than in groups 1 and 2. No significant differences were seen in LV muscle mass and wall thickness between groups 2 and 3. A significant inverse correlation was seen between ejection fraction and end-systolic stress in patients with DC (Y = -0.05x + 48.7, r = 0.57, p less than 0.01). The slope of the correlation line between end-systolic stress and volume in DC (Y = 1.20x + 135, r = 0.52, p less than 0.02) was less steep than that of normal subjects (Y = 3.68x + 40, r = 0.64, p less than 0.001). These observations indicate that the primary problem of DC is depressed contractility.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗