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Biomedical subjects

K Yasuda

Publications and source records attributed to K Yasuda.

At least 577 records · Page 32Linked to original sources
PubMed1995

Hepatitis C virus genotypes and development of hepatocellular carcinoma.

BACKGROUND: Among several genotypes of hepatitis C virus (HCV), genotypes 1b (or II) and 2a (or III) are predominant in Japan. Although it has been shown that the efficacy of interferon treatment of patients with chronic hepatitis C varies with the HCV genotype, the relationship between HCV genotype and the development of hepatocellular carcinoma (HCC) has not been well described. METHODS: The genotypes and serum levels were determined for HCV-RNA in 72 patients with HCC and 131 patients without HCC, all of whom were positive for second-generation HCV antibody and HCV-RNA. In addition, clinical data from 34 patients with HCC who each had a history of blood transfusion were analyzed. RESULTS: Fifty-seven (79.2%) of 72 patients with HCC had genotype 1b HCV, whereas 101 (77.1%) of 131 patients without HCC had genotype 1b, indicating that there was no significant difference in the prevalence of genotype 1b HCV between the patients with and without HCC. Furthermore, comparison of patients with HCC with genotype 1b HCV with those with genotype 2a who had a history of blood transfusion did not differ significantly in the number of years from blood transfusion to diagnosis of HCC. Levels of HCV-RNA were not significantly different among patients with liver diseases of various stages. CONCLUSIONS: Hepatocellular carcinoma develops in patients with either genotype 2a HCV or genotype 1b HCV. A difference in genotype is not likely to be responsible for the difference in development of HCC.

Carcinoma, Hepatocellular↗
PubMed1995

A mutation in the beta 3-adrenergic receptor gene is associated with obesity and hyperinsulinemia in Japanese subjects.

The Trp 64 Arg mutation in the beta 3-adrenergic receptor (beta 3AR) gene was investigated in 350 Japanese subjects. This mutation was not associated with non-insulin-dependent diabetes mellitus (NIDDM). In 191 subjects without NIDDM, body mass index (BMI) was significantly higher in subjects homozygous for this mutation than in those homozygous for the normal allele (24.7 +/- 1.4 vs 22.1 +/- 0.2 kg/m2, p = 0.009). Moreover, the frequency of the mutant allele in obese subjects (BMI > 26.4) was significantly higher than that in non-obese subjects (BMI < 22) (0.37 vs 0.15, p = 0.009). The presence of this mutation was also accompanied by significantly higher fasting (p = 0.000) and 2 hrs (p = 0.018) serum insulin levels during an oral glucose tolerance test. The beta 3AR may be one of the loci contributing to obesity and hyperinsulinemia/insulin resistance in Japanese subjects.

Adult↗
PubMed1995

No evidence for mutations in a putative subunit of the beta-cell ATP-sensitive potassium channel (K-ATP channel) in Japanese NIDDM patients.

The ATP-sensitive K channel (K-ATP channel) in pancreatic beta cells is believed to play a crucial role in glucose-stimulated insulin release. We investigated whether defects in the recently cloned gene for a putative subunit of this channel (KATP-2) could be a cause of diabetes in Japanese patients. The coding region of this beta-cell type channel gene was investigated in 192 diabetics with a family history of the disorder by single-stranded conformational polymorphism (SSCP) analysis. Two silent polymorphisms were found and confirmed by sequencing, but no missense or nonsense mutations were detected. The allele frequency of the polymorphisms was compared with 96 control subjects without a family history of the disease, and no clear difference was found. These results indicate that genetic defects of the KATP-2 channel may not be a major cause of diabetes in Japan.

Adult↗
PubMed1995

Micturitional disturbance in myotonic dystrophy.

Micturitional disturbance has attracted little attention in myotonic dystrophy, but detailed micturitional histories revealed that two out of six patients (33%) had micturitional symptoms. One had difficulty urinating and the other had urinary frequency, urgency and stress incontinence. Urodynamic studies were performed in all patients and the results were as follows: Two had low maximum urethral closure pressure, two had large and three had small bladder capacities, one had detrusor hyperreflexia and one had atonic cystometrogram. Urethral sphincter electromyography revealed a decreased bulbocavernosus reflex in one, and an absent anal reflex in two. Motor unit analysis of external sphincter was performed with one patient and showed polyphasic potentials. Dystrophic changes of the lower urinary tract muscles, as well as supranuclear type of pelvic nerve dysfunction, could cause micturitional disturbance in patients with myotonic dystrophy.

Adult↗
PubMed1995

Molecular biology of somatostatin receptors.

The diverse physiological effects of somatostatin are mediated by a family of cell surface receptors that bind somatostatin selectively and with high affinity. The somatostatin receptors are members of the seven transmembrane segment receptor superfamily and molecular cloning studies have identified five types, designated sstr1-5. The human somatostatin receptors vary in size from 364 (sstr5) to 418 (sstr3) amino acids with 46-61% amino acid identity between receptors, and 105 amino acids are invariant. The sequences of the seven putative alpha-helical membrane-spanning domains are more highly conserved than those of the extracellular N- and intracellular C-terminal domains. Two forms of sstr2 have been identified in the mouse, sstr2A and sstr2B, which differ in size and sequence of the intracellular C-terminal domain. These two forms of sstr2 are products of a common gene and are generated by alternative splicing with sstr2A and sstr2B being the products of the unspliced and spliced forms, respectively, of sstr2 mRNA. Thus, functional diversity within the somatostatin receptor family may result from the expression of multiple types as well as from alternative splicing. The five somatostatin receptors have distinct patterns of expression in the central nervous system and peripheral tissues. They have also been expressed in vitro and shown to have different pharmacological properties. Somatostatin analogues selective for sstr2, sstr3 and sstr5 have been identified which will facilitate in vivo studies of the functions of these somatostatin receptors. Such studies to date suggest that sstr2 mediates inhibition of growth hormone secretion and sstr5 mediates inhibition of insulin secretion. The molecular cloning and functional characterization of the somatostatin receptor family is a first step in elucidating the diverse effects of somatostatin on cellular functions.

Amino Acid Sequence↗
PubMed1995

Dominant replication of either virus in dual infection with hepatitis viruses B and C.

To characterize the state of dual infection with hepatitis B virus (HBV) and hepatitis C virus (HCV), HBV-DNA and HCV-RNA levels were determined by spot hybridization or polymerase chain reaction in the sera of patients who were positive for both hepatitis B surface antigen and HCV antibody. Among 27 patients who showed evidence of double infection, 21 (77.8%) had detectable levels of only either HBV or HCV genome in their sera, 2 (7.4%) showed none of the viral genomes, and 4 (14.8%) had both HBV-DNA and HCV-RNA. In the 4 patients with both HBV-DNA and HCV-RNA, the titers of HCV-RNA or HBV-DNA were lower than those in the patients with HCV-RNA or HBV-DNA alone. In some patients with chronic hepatitis, the viruses appeared to replicate in turn in the course of the disease. These results indicate that the viruses show alternating dominance in replication in most of the patients who have dual infection with HBV and HCV, probably due to interference of the viruses.

Adolescent↗
PubMed1995

A subtype of diabetes mellitus associated with a mutation in the mitochondrial gene.

Recently, in patients with diabetes and deafness, researchers have identified an A to G transition at position 3243 in transfer ribonucleic acid(Leu)(UUR) [3243 base-pair (bp) mutation], originally found in patients with mitochondrial myopathy, encephalopathy, lactic acidosis, and strokelike episodes. To determine the prevalence of diabetic patients with this mutation in Japan, we screened selected cohorts of diabetic patients based upon type of diabetes, family history of diabetes, and age of onset; also screened were 550 unselected cohorts of diabetic patients, without prior information. We identified 5 patients with the 3243-bp mutation, suggesting that approximately 0.9% of diabetic patients have it. However, there were none with this mutation in 250 controls with normal glucose tolerance. We also studied the clinical characteristics and insulin secretory characteristics of diabetic patients with 3243-bp mutation. We propose that diabetes mellitus with 3243-bp mutation is a novel subtype of diabetes mellitus, maternally inherited diabetes, and deafness (MIDD).

Adult↗
PubMed1995

Alterations in coagulation and fibrinolysis after surgery for aortic aneurysm.

We investigated the alterations in the coagulation and fibrinolysis systems after aortic aneurysm surgery under cardiopulmonary bypass (CPB) while using newly developed "molecular markers". Fibrinogen and antithrombin III (AT-III) decreased after surgery but returned to normal values within three days. The thrombin-antithrombin III complex (TAT) and plasmin-alpha-2-plasmin inhibitor complex (PIC) both showed increased values even preoperatively, which indicated that coagulation and fibrinolysis were activated in some patients with an aortic aneurysm. Both markers maintained a high level for at least 14 days after surgery. The fibrin degradation product (FDP) also showed an increased value before and after surgery. These results apparently showed that coagulation/fibrinolysis had already been activated in some patients and maintained such a state for at least 14 days after surgery. The relation of activated system and postoperative organ dysfunction as well as the means to suppress such activation are also discussed.

Aged↗
PubMed1995

Preoperative disseminated intravascular coagulation (DIC) associated with aortic aneurysm--does it need to be corrected before surgery?

Disseminated intravascular coagulation (DIC) is one of the complications accompanying aortic aneurysm. We herein report four patients with aortic aneurysm who had DIC preoperatively. In all four cases, DIC was corrected immediately after surgery; however, in two cases, DIC could not be corrected preoperatively. This prompted us to reconsider the importance of correcting DIC before surgery. Of the four cases reported in this paper, DIC existed even at the time of surgery in two cases, in spite of meticulous treatment with heparin and/or protease inhibitor; however, the DIC could be removed postoperatively even in these two cases. Surgeons should not waste time with intensive DIC treatment preoperatively. If the DIC cannot be corrected within more than 2 weeks of meticulous treatment, surgeons should then perform surgery on the patient. In addition, it is also essential to ensure that the DIC is due to the aneurysm itself and that no other disease processes have been overlooked.

Aged↗
PubMed1995

Detection of anti-cord factor antibodies in intestinal tuberculosis for its differential diagnosis from Crohn's disease and ulcerative colitis.

We have developed a diagnostic method for pulmonary tuberculosis by detecting antibody to cord factor using enzyme-linked immunosorbent assay (ELISA). This study was to evaluate the usefulness of our method for a diagnosis of intestinal tuberculosis, and especially its ability to differentiate this disease from other inflammatory bowel diseases. Antibodies of the immunoglobulin G class against cord factor (trehalose-6,6'-dimycolate) from 27 patients with intestinal tuberculosis, 16 patients with Crohn's disease (CD), and 27 patients with ulcerative colitis (UC) were tested by ELISA with cord factor purified from Mycobacterium tuberculosis H37Rv as the antigen. Twenty-three of the 27 patients with intestinal tuberculosis (85%) showed elevated values distinct from healthy controls. None of the patients with CD showed an elevation of antibody titers. Of the 27 patients with UC, 26 (96%) did not show any anti-cord factor antibody elevation. We conclude that this method is simple and results are reproducible. The results of our study justify undertaking the detection of anti-cord factor antibodies to diagnose intestinal tuberculosis.

Adult↗
PubMed1995

Hyperresponse in calcium-induced insulin release from electrically permeabilized pancreatic islets of diabetics GK rats and its defective augmentation by glucose.

In spontaneously diabetic GK rats, insulin secretion from pancreatic beta cells in response to glucose is selectively impaired, probably due to deficient intracellular metabolism of glucose and impaired closure of KATP channels during glucose stimulation. By using electrically permeabilized islets of GK rats, we explored the functional modulations in exocytotic steps distal to the rise in [Ca2+]i in the diabetic condition. At 30 nmol/l Ca2+ (basal conditions) insulin release was similar between GK and non-diabetic control Wistar rats. In response to 3.0 mumol/l Ca2+ (maximum stimulatory conditions), insulin release was significantly augmented in permeabilized GK islets (p < 0.01). Raising glucose concentrations from 2.8 to 16.7 mmol/l further augmented insulin release induced by 3.0 mumol/l Ca2+ from permeabilized control islets (p < 0.001), but had no effect on that from permeabilized GK islets. The stimulatory effect of glucose on insulin release from permeabilized control islets was partly inhibited by 2,4-dinitrophenol, an inhibitor of mitochondrial oxidative phosphorylation (p < 0.01). The hyperresponse to Ca2+ in GK islets may play a physiologically compensatory role on the putative functional impairment both in [Ca2+]i rise and energy state in response to glucose in diabetic beta cells, and may explain the relative preservation of insulin release induced by non-glucose depolarizing stimuli, such as arginine, from pancreatic islets in non-insulin-dependent diabetes mellitus.

2,4-Dinitrophenol↗
PubMed1995

Hypoaminotransferasemia in patients undergoing long-term hemodialysis: clinical and biochemical appraisal.

BACKGROUND & AIMS: It has been reported that patients with chronic renal failure have low serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels as a result of vitamin B6 deficiency. Chronic hepatitis C is common among patients undergoing hemodialysis, and low aminotransferase levels cause diagnostic problems. The aim of this study was to determine the cause of hypoaminotransferasemia. METHODS: Serum levels of vitamin B6 and its coenzyme were reassessed in relation to AST and ALT levels in patients undergoing long-term hemodialysis using high-performance liquid chromatography. RESULTS: The mean (+/- SD) serum AST and ALT levels in 304 patients negative for hepatitis B surface antigen and anti-hepatitis C virus were 9.2 +/- 2.4 and 7.4 +/- 1.7 IU/L, respectively. In 556 normal adults, they were 22.7 +/- 5.4 and 18.0 +/- 4.0 IU/L, respectively (P < 0.001). Mean serum vitamin B6 and pyridoxal-5'-phosphate levels in patients undergoing dialysis were not reduced compared with the control, although occasionally patients had low levels. The AST and ALT assay reagents in Japan do not contain added pyridoxal-5'-phosphate; addition of pyridoxal-5'-phosphate (0.1 mmol/L) to the reagent significantly increased measurements to similar extents in both groups. CONCLUSIONS: Serum AST and ALT levels in patients undergoing dialysis are very low, but they are not a result of vitamin B6 deficiency. The upper normal limits of AST and ALT levels in patients undergoing dialysis should be reduced considerably, and these levels should be interpreted with caution in the diagnosis of liver disease.

Adult↗
PubMed1995

Effect of dexamethasone and prednisolone on insulin-induced activation of protein kinase C in rat adipocytes and soleus muscles.

We examined the effect of glucocorticoids on [3H]2-deoxyglucose ([3H]2-DOG) uptake, [125I]insulin binding, tyrosine kinase activity, and protein kinase C (PKC) activity in rat adipocytes and soleus muscles. In adipocytes, insulin-stimulated [3H]2-DOG uptake was decreased by prior 60-minute treatment with dexamethasone (DEX) or prednisolone (PSL), whereas [125I]insulin binding, insulin (INS) receptor autophosphorylation, and tyrosine kinase activity, as measured using exogenous substrate of poly(Glu80-Tyr20), were not significantly changed. Cytosolic PKC activity decreased and membrane-associated PKC activity increased during a 60-minute treatment of adipocytes and soleus muscles with DEX or PSL, indicating that both DEX and PSL stimulate the translocation and activation of PKC. However, pretreatment of adipocytes and soleus muscles with glucocorticoids resulted in reduced INS-stimulated translocation of PKC from cytosol to membrane. INS-induced decreases in cytosolic PKC activity (50% +/- 7% v 10% +/- 8% and 20% +/- 7%, P < .05 to .01, for nonpretreated [control], DEX pretreated, and PSL pretreated cells) and increases in membrane PKC (100% +/- 10% v 50% +/- 9% and 20% +/- 9%, P < .01, for control, DEX pretreated, and PSL pretreated cells) were larger in nonpretreated adipocytes than in adipocytes pretreated with glucocorticoids. These results raise the possibility that glucocorticoids, namely, DEX and PSL, stimulate the translocation and subsequent degradative downregulation of PKC, and that this may be pertinent to their inhibitory effects on INS-stimulated glucose transport.

Adipose Tissue↗
PubMed1995

Formation of 6 beta-OH-deoxycorticosterone from deoxycorticosterone by A6 cells.

We have investigated the metabolism of deoxycorticosterone in A6 cells, a continuous cell line derived from the kidney of Xenopus laevis. A6 cells at confluence were incubated with serum-free culture media containing 2.5 microM [3H] deoxycorticosterone. When radioactive compounds in incubation media were separated by reverse-phase high-pressure liquid chromatography, the formation of polar metabolites was observed. One component of polar metabolites cochromatographed with 6 beta-hydroxydeoxycorticosterone. In order to identify this component more rigorously, large scale cultures were performed and this compound was separated and purified by reverse-phase high-pressure liquid chromatography. The purified material was analyzed by gas chromatography-mass spectrometry, secondary ion mass spectrometry, and nuclear magnetic resonance spectroscopy. These procedures revealed that this material was 6 beta-hydroxydeoxycorticosterone.

Animals↗
PubMed1995

Neutrophil-independent myocardial dysfunction during an early stage of global ischemia and reperfusion of isolated hearts.

The effect of global ischemia and reperfusion on the expression of cytokine genes and cell adhesion molecules by myocardial tissues and neutrophils was studied by using the Langendorff model. Although cardiac function deteriorated after reperfusion of ischemic hearts, there was no evidence of inflammation and myocardial degeneration, which is in contrast to previous findings that neutrophil-mediated inflammation is a critical step in post-ischemic reperfusion injury in regional ischemia. Flow cytometry analysis demonstrated that the global ischemia and reperfusion did not affect the expression of adhesion molecules on neutrophils. We also examined the expression of various cytokines which are involved in inflammatory responses. Only interleukin 1 alpha was induced after the reperfusion of the ischemic hearts. These results suggest that neutrophils barely contribute to the myocardial dysfunction and IL-1 alpha may play a role in post-ischemic myocardial dysfunction during the early stage of reperfusion.

Animals↗
PubMed1995

Effects of wortmannin on glucose uptake and protein kinase C activity in rat adipocytes.

Wortmannin is known to be an inhibitor of myosin light chain kinase and phosphatidylinositol 3-kinase (PI 3-kinase) (J. Biol. Chem. 268, 25846, 1993). We studied the effects of wortmannin on insulin- and 12-O-tetradecanoylphorbol 13-acetate (TPA)-induced glucose uptake, purified PKC activity and in vitro 80 kDa protein phosphorylation to elucidate the relationship between insulin-induced PI 3-kinase and PKC activations. Pretreatment with 10(-12)-10(-6) M wortmannin for 60 min resulted in a dose-responsive reduction of 10 nM insulin-stimulated glucose uptake in rat adipocytes. Pretreatment with 10(-6) M wortmannin resulted in 80% and 20% decreases of glucose uptake stimulated by insulin and TPA, respectively. Partially purified rat brain PKC activity and 80 kDa protein in vitro phosphorylation of rat adipocyte cytosol by addition of Ca2+ and phospholipid were dose-dependently decreased by 10(-8)-10(-6) M wortmannin; 20% decrease of PKC activity and 50% decrease of 80 kDa protein phosphorylation by 10(-6) M wortmannin were observed. These results suggest that wortmannin has a potent inhibitory effect on PI 3-kinase and a weak inhibitory effect on PKC activity, and both effects cause a significant inhibition of insulin-stimulated glucose uptake in rat adipocytes.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗
PubMed1995

Balloon angioplasty before Wheat's operation in a patient with Turner's syndrome.

The case of a 19-year-old woman with Turner's syndrome, dissecting aneurysm of the ascending aorta, coarctation of the aorta and bicuspid aortic valve stenosis is presented. Balloon angioplasty was performed before surgery to relieve the pressure gradient caused by coarctation of the aorta. Successful surgical treatment was carried out using Wheat's method. Four-year follow-up has revealed no signs of complications such as restenosis or aneurysm formation.

Adult↗