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Biomedical subjects

K Kaku

Publications and source records attributed to K Kaku.

At least 91 records · Page 5Linked to original sources

Antihypertensive and metabolic effects of long-term treatment with amosulalol in non-insulin dependent diabetics.

In this open study, 41 hypertensive patients with non-insulin dependent diabetes mellitus were treated with the combined alpha- and beta-adrenoceptor blocker amosulalol hydrochloride for 24 weeks, either alone or added to existing antihypertensive therapy. The effects on blood pressure, glucose and lipid metabolism were examined. Daily administration of 20 to 60 mg amosulalol caused a significant reduction in both systolic and diastolic blood pressure within 2 weeks. This effect was stable, lasting for the entire trial period. The mean systolic and diastolic blood pressure decreased from 174 +/- 13/92 +/- 9 mmHg at the beginning to 148 +/- 16/80 +/- 11 mmHg at the end of the trial. Heart rate was not affected. Plasma glucose and haemoglobin Alc levels showed a tendency to decrease without any statistical significance. Total and HDL-cholesterol and triglyceride levels also remained unchanged. Although 3 patients had complained of dizziness, all were easily manageable. The results indicate that amosulalol is effective in the treatment of hypertension in non-insulin dependent diabetics and does not affect glucose and lipid metabolism.

Adult↗

Tolbutamide inhibits cAMP-dependent phosphorylation of liver 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase.

The activity of a bifunctional enzyme, liver 6-phosphofructo-2-kinase (PFK-2)/fructose-2,6-bisphosphatase (F-2,6-Pase), which regulates the level of liver fructose-2,6-bisphosphate (F-2,6-P2), the most potent activator of PFK, is modulated by its phosphorylation rate mainly catalyzed by cAMP-dependent protein kinase A (PKA). To elucidate the action mechanism of sulfonylurea on liver F-2,6-P2 production, effects of tolbutamide on PKA-dependent phosphorylation of purified liver PFK-2/F-2,6-Phase protein and on kinase and phosphatase activities of the purified enzyme were examined in vitro. The purified enzyme was phosphorylated in the presence of the catalytic subunit of PKA, and tolbutamide inhibited the enzyme phosphorylation catalyzed by PKA in a dose-dependent manner. By adding the same dosages of tolbutamide used in the phosphorylation experiment, reduced activity of PFK-2 and increased activity of F-2,6-Pase in the presence of PKA were restored to the levels observed in the absence of PKA. On the other hand, carboxytolbutamide, an inactive metabolite of tolbutamide, had little effect on enzyme phosphorylation and activity. Our results indicate that tolbutamide inhibits a phosphorylation of the liver PFK-2/F-2,6-Pase catalyzed by PKA along with an activation of PFK-2 and an inactivation of F-2,6-Pase, leading to liver F-2,6-P2 production.

Animals↗

Effect of erythroid differentiation factor on megakaryocytic differentiation of L8057, a murine megakaryoblastic leukemia cell line.

To assess the potent effect of erythroid differentiation factor (EDF) on megakaryocytopoiesis, effect of EDF on megakaryocytic differentiation of L8057, a murine megakaryoblastic cell line, was examined. EDF potentiated AchE induction of L8057 in a dose dependent manner. The potency of EDF on megakaryocytic differentiation is comparable to that on erythroid differentiation reported previously. The present results suggest that EDF may play a regulatory role in megakaryocytopoiesis as well as in erythropoiesis.

Acetylcholinesterase↗

Possible mechanism of proteolysis for the extrapancreatic action of tolbutamide.

In order to assess the mode of the extrapancreatic action of the sulfonylureas, we evaluated the contribution of a proteolytic mechanism for sulfonylurea action by analyzing the effects of a protease inhibitor on insulin- or tolbutamide-stimulated liver fructose-2,6-bisphosphate (F-2,6-P2) formation using isolated rat hepatocytes. The F-2,6-P2 level in hepatocytes was significantly increased by the addition of insulin or tolbutamide. The stimulatory effect of insulin on the F-2,6-P2 formation was most significant when its level was reduced by the addition of 2 microM of forskolin. Insulin action on F-2,6-P2 formation was inhibited by the addition of a protease inhibitor, p-tosyl-L-arginine methyl ester hydrochloride (TAME). Tolbutamide (2 mM) significantly increased hepatocyte F-2,6-P2 level (P less than 0.01 vs the control level). In the presence of TAME, the stimulatory effect of tolbutamide was also suppressed. The present data suggest that a proteolytic mechanism is important in both insulin and tolbutamide action on the F-2,6-P2 formation, and it may be hypothesized that, like insulin, the chemical mediator of tolbutamide action is formed proteolytically.

Animals↗

Sulfonylurea enhances insulin-induced acetyl coenzyme A carboxylase activity in rat adipocytes.

The effect of sulfonylurea on the activity of acetyl-coenzyme A carboxylase, a rate limiting enzyme of lipogenesis, was investigated using isolated rat adipocytes. Insulin significantly increased the enzyme activity by 170% of the control level, while glucagon and epinephrine decreased the activity of the enzyme by 53% and 64% of the control, respectively. In the presence of tolbutamide (10(-3) M) or glibenclamide (10(-6) M), a significant potentiation of insulin action was found in adipocytes. In addition, sulfonylurea restored the activity of acetyl-CoA carboxylase reduced by glucagon or epinephrine to the control level. Sulfonylurea enhancement of the acetyl-CoA carboxylase activity may offer one possible explanation for a mechanism of antilipolytic action of the drug in adipocytes.

Acetyl-CoA Carboxylase↗

[VAD regimen for multiple myeloma--the effectiveness as first line therapy].

VAD regimen, combining vincristine, doxorubicin, and dexamethasone was given to 6 previously untreated and 4 treated patients with multiple myeloma. The response rate was obtained in 67% of previously untreated patients and in 50% of previously treated patients. In responders, a rapid improvement of clinical symptoms accompanied with a significant decrease in M-protein was observed. Patients with response to VAD therapy were received melphalan and prednisolone as maintenance. Response duration ranged between 4 months and 38 months. The infectious episodes were occurred in 36.8% patients but none of these was serious. The present results suggest that VAD regimen is useful as primary treatment for multiple myeloma when rapid control of disease is necessary.

Adult↗

Square root sign of left ventricular diastolic pressure curve in atrial septal defect.

The square root (dip and plateau) sign was observed in 7 of 21 adult patients with atrial septal defect (ASD). This study evaluated left ventricular (LV) diastolic filling dynamics and hemodynamic findings in 7 patients (Group 1) with, and 14 patients (Group 2) without the square root sign; 10 normal subjects (Group 3) served as controls. No significant differences were observed in LV end-diastolic and end-systolic volumes, ejection fraction, or left to right shunt. In Group 1, 77% of LV filling was completed in the first half of diastole; this percentage was 49% and 53% in Groups 2 and 3, respectively (both p less than 0.01 versus Group 1). Early diastolic filling velocity (at 20% of diastole) in Group 1 was significantly greater, and late diastolic filling velocity (at 80% and 90% of diastole) was reduced in Group 1 compared to those in Groups 2 and 3 (all p less than 0.05). The average values for right and left ventricular end-diastolic pressures were significantly higher in Group 1 (11 +/- 2 and 10 +/- 4 mmHg, p less than 0.05) than Group 2 (7 +/- 2 and 7 +/- 2 mmHg, p less than 0.05). It is suggested that a constrictive pathophysiology due to 4 chambers interaction or right ventricular constraint may play a role in the genesis of the square root sign in ASD.

Adolescent↗

An in vitro evaluation of adrenergic action on rat pancreatic amylase secretion: lack of stimulatory effect.

To assess direct evidence of adrenergic stimulation in pancreatic amylase secretion, effects of catecholamines on amylase release and intracellular cyclic AMP accumulation were examined with rat dispersed pancreatic acini. We first carried out control studies with CCK-8 and carbamylcholine to evaluate the usefulness of the material for the examination of amylase secretion, and examined VIP-induced cyclic AMP accumulation to assess the agonist evoked intracellular response. As a result, significant effects of CCK-8, carbamylcholine and VIP were observed, which confirmed that dispersed pancreatic acini used in this study were useful in examining exocrine pancreatic secretion. However, catecholamines failed to stimulate amylase release from pancreatic acini, although a significant increase in intracellular cyclic AMP accumulation was observed. Thus the present study strongly suggests that direct involvement of catecholamine is unlikely in pancreatic amylase secretion, in contrast to results reported previously.

1-Methyl-3-isobutylxanthine↗

Polymorphisms of HepG2/erythrocyte glucose-transporter gene. Linkage relationships and implications for genetic analysis of NIDDM.

To assess the contribution of the HepG2/erythrocyte glucose-transporter (HepG2 GT) gene to the inherited susceptibility to non-insulin-dependent diabetes mellitus (NIDDM), cDNA and genomic probes were used to search for restriction-endonuclease polymorphisms at this locus. Analysis of DNA from 16 unrelated Black American individuals with 19 enzymes and as many as six different probes, defined four polymorphisms over a 45-kilobase region. Nucleotide diversity (pi = 0.006) was low relative to that at other loci, with an average of 1 in 1700 base pairs different between two chromosomes at this locus. The observed combined heterozygosity for these four sites was 0.69, which indicates that the markers at this locus could be useful for linkage analysis in families. Linkage-disequilibrium values between the four polymorphisms were evaluated by pairwise analysis and extended haplotypes. Calculating pairwise associations by the disequilibrium statistic delta or by another measure of disequilibrium, D' (the maximum likelihood of disequilibrium, which is less dependent on frequency), significant linkage disequilibrium could not be demonstrated. However, the frequencies of the observed extended haplotypes were shown to differ (chi 2 = 9.1, df = 2, P less than 0.025) from predicted frequencies if the sites were in linkage equilibrium in Blacks. The frequencies of these four polymorphisms were determined in Black nondiabetic (n = 44) and NIDDM (n = 63) subjects. Neither the allelic nor genotypic frequencies of the polymorphisms differed between the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Black People↗

[Intrapericardial bronchogenic cyst--a report of two surgical cases].

Two cases of intrapericardial bronchogenic cyst are reported. Case 1 was a 58-year-old man with a complaint of exertional dyspnea. A chest X-ray film showed a right hilar mass shadow. Echocardiographically the mass showed cystic pattern in the pericardium. A pulmonary angiogram revealed a mass displacing the right pulmonary artery superiolaterally and left atrium and pulmonary vein inferiorly. The preoperative diagnosis was intrapericardial cyst. Subtotal resection of intrapericardial cyst was performed via right thoracotomy. Histological diagnosis was bronchogenic cyst. The postoperative course was uneventful. Case 2 was a 41-year-old man. A displacement of the esophagus and duodenal ulcer was pointed out in the upper gastrointestinal series. A chest X-ray film showed a right hilar mass shadow. Since echocardiogram and pulmonary angiogram revealed similar findings to those in case 1, intrapericardial bronchogenic cyst was suspected preoperatively. Complete resection of the intrapericardial cyst was made via right thoracotomy. Histological diagnosis was bronchogenic cyst. The postoperative course was uneventful.

Adult↗

[Clinical experience with chemotherapy using sulbactam/cefoperazone for severe infections accompanying malignant hematological disorders].

Clinical and bacteriological efficacies of sulbactam/cefoperazone (SBT/CPZ) were studied in 44 patients with serious infections associated with hematological malignancy. 1. SBT/CPZ was clinically effective in 33 cases (76.7%). Excellent effects were obtained in 23 cases, good effects in 10 cases and fairly good effects in 7 cases. Clinical effectiveness of SBT/CPZ was not dependent on neutrophil number in peripheral blood. 2. Bacteriologically SBT/CPZ was effective against all of the isolated organisms from 21 cases. 3. Adverse reactions were not significant except one case with eruption, 2 cases with abnormalities in hepatic function tests and 3 cases with abnormalities in renal function tests.

Adolescent↗

[Non-Hodgkin's lymphoma arising from the wall of old tuberculous empyema--a surgical case report].

A 71-year-old male underwent therapeutic pneumothorax for left pulmonary tuberculosis 42 years ago. He visited our hospital in February 1988 with a complaint of hemosputum. In October, cytology of sputum revealed malignant cells, and the patient was admitted to our hospital for further examination. Because malignant cells were found by the left bronchial lavage, pan-pleuropneumonectomy was performed on January 12, 1989 under the diagnosis of left lung cancer. The tumor was partially left unremoved. Histological diagnosis was diffuse large cell type, B cell non-Hodgkin's lymphoma. Postoperatively, 2 courses of cyclophosphamide, adriamycin, vincristine, prednisone, etoposide (CHOP and VP-16) therapy were performed. However, the patient died of respiratory insufficiency on the 125th postoperative day. Recently, cases of malignant lymphoma involving the pleura after the old tuberculous empyema and therapeutic pneumothorax have been increased. Therefore, prompt diagnosis and treatment are recommended when tumor shadow is suspected as a result of imaging examination.

Aged↗