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Biomedical subjects

Y Sakai

Publications and source records attributed to Y Sakai.

At least 613 records · Page 34Linked to original sources
PubMed1991

Contractile responses and calcium mobilization in renal arteries of diabetic rats.

The causes of diabetes-associated change of renal artery vasomotion have not been established. We investigated both contractile responses to KCl and norepinephrine (NE) in renal arteries of rats with streptozotocin-induced diabetes and age-matched controls and the effects on Ca2+ mobilization. Renal arteries from diabetics had greater maximum contractile responses to KCl and NE, but the threshold concentrations and EC50 values of KCl and NE were similar in controls and diabetics. The concentration-response for Bay K 8644, a dihydropyridine Ca2+ channel agonist in the presence of 20 mM KCl was significantly greater in diabetics than in controls. The maximum contractile responses to Ca2+ in the presence of 10(-6) M NE were significantly (P less than 0.05) greater in diabetics than in controls. The increased contractile response at low concentrations of Ca2+ (0.01-0.05 mM) was inhibited in both preparations by 10(-6) M nifedipine, but at high concentrations of Ca2+ (0.1-2.5 mM) the inhibition by nifedipine was significantly less in diabetics than in the controls. 45Ca2+ uptake had significantly greater resting levels in diabetics than in controls. The uptake of 45Ca2+ induced by 10(-5) M NE was significantly greater in diabetics than in controls, and 10(-7) M prazosin diminished both responses. The results suggest hyperreactivity of contractile responses to KCl or NE, and hyperpermeability of renal artery smooth muscle membrane to Ca2+ in streptozotocin-induced diabetics.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1991

Endogenous angiotensin II receptors in Xenopus oocytes and eggs.

Angiotensin II (AII) induced strongly desensitizing oscillatory Cl- inward currents in both follicle-enclosed and collagenase-treated Xenopus oocytes. The AII response was abolished by EGTA and attenuated by pertussis toxin. Treatment of oocytes with collagenase transiently reduced both the ratio of oocytes responsive to AII and the amplitude of AII responses, followed by restoration to original levels in 3-4 days. The response to adrenaline, which is mediated by endogenous beta-adrenoceptors in follicle cells, however, was irreversibly abolished by collagenase treatment. These results suggest that endogenous current-mediating AII receptors in oocytes are coupled with phosphatidylinositol hydrolysis and localized in the oocyte or in a cellular structure distinct from that for endogenous beta-adrenoceptors. Progesterone-matured Xenopus eggs also responded to AII, and this AII-induced depolarization resembled the fertilization potential in the eggs, suggesting a possible role of AII receptors in processes of fertilization or growth of the eggs.

Acetylcholine↗
PubMed1991

Desensitization of endogenous angiotensin II receptors in Xenopus oocytes: a role of protein kinase C.

The inward chloride current induced by angiotensin II (AII) in Xenopus oocytes shows strong and homologous desensitization, and was suggested to be mediated by phosphatidylinositol (PI) hydrolysis (Sakuta et al., 1991, Eur. J. Pharmacol. Mol. Pharmacol. 208, 31). As a model of agonist-induced desensitization of receptors coupled with PI hydrolysis, the mechanism of the desensitization of endogenous AII receptors in oocytes was investigated. Incubation of collagenase-treated oocytes with staurosporine significantly augmented the peak amplitude of AII responses, prolonged their duration, and increased the ratio of oocytes responsive to AII. Moreover, staurosporine-pretreatment made oocytes be consistently responsive to every application of AII. These effects of staurosporine were inhibited by incubation of staurosporine-treated oocytes with 12-O-tetradecanoylphorbol 13-acetate (TPA) but not with dibutyryl cAMP. TPA also attenuated AII responses in staurosporine-untreated control oocytes. These results suggest that staurosporine suppresses the desensitization of endogenous AII receptors in oocytes by blocking protein kinase C (PKC), and the desensitization is likely to be due to phosphorylation by PKC of the receptors or the molecules comprising an AII receptor complex.

Acetylcholine↗
PubMed1991

Sodium pump activity and contraction of renal artery from spontaneously hypertensive rats.

We investigated the hypertensive changes in renal arteries isolated from 21-week-old spontaneously hypertensive rats (SHR), and from age-matched normotensive Wistar-Kyoto rats (WKY). The maximum contraction of renal arteries from SHR in response to norepinephrine (NE), serotonin (5-HT) and KCl was greater than that of arteries from WKY. The threshold and EC50 concentrations of NE, 5-HT and KCl were not significantly different between SHR and WKY. Contraction induced by removal of K+ was inhibited by 10(-8) M prazosin. Less than 10(-7) M NE in K(+)-free solution did not cause contraction. Addition of 5.9 mM KCl to K(+)-free solution in the presence of 10(-5) M NE induced relaxation, which was followed by contraction to about the same level as that before KCl addition. The duration of the K(+)-induced relaxation in SHR (22.4 +/- 0.9 min) was slightly, but significantly shorter than that in WKY (26.6 +/- 0.8 min) arteries. In K(+)-free solution with reduced Na+, the duration of the relaxation induced by KCl was shorter than that in the normal solution, for both SHR (13.8 +/- 0.3 min) and WKY (14.1 +/- 0.5 min). Such differences could be caused by increased influx and decreased efflux of Ca2+, which depend on the Na+ concentration and are related to the Na(+)-Ca2+ exchange. The results suggest that enhanced renal vascular reactivity in hypertension may depend on structural changes and increased Na+ pump activity.

Animals↗
PubMed1991

Factors associated with high density lipoprotein cholesterol in Japanese and American telephone executives.

The association of plasma high density lipoprotein cholesterol (HDL cholesterol) with several factors was examined in a cross-sectional study of Japanese and American telephone executives. Mean HDL cholesterol levels were similar in both groups of men and were negatively associated with body mass index, smoking, and serum uric acid and positively associated with alcohol and exercise. These associations did not differ between the Japanese and the American men. The mean HDL cholesterol level was 4.2 mg/dl lower in the Japanese than in the American men after adjusting for age, body mass index, alcohol, smoking, exercise, and serum uric acid. The difference in HDL cholesterol between Japanese and American men in this study is inconsistent with the much lower coronary heart disease mortality in Japan and with previous comparison studies of these two populations. Most previous studies have not adjusted for important confounders, but the selective nature of our study groups may have also contributed to this inconsistency. These racial differences in HDL cholesterol may also be due to either genetic or unmeasured environmental and cultural differences. Given the similarity in HDL cholesterol levels between these two groups, our results suggest that HDL cholesterol does not play an important role in the lower coronary heart disease mortality in Japanese men.

Adult↗
PubMed1991

Cloning and sequence analysis of a cDNA encoding human non-selective type of endothelin receptor.

A cDNA encoding non-selective type (ETB) of endothelin receptor was isolated from a human liver cDNA library. The cDNA had an open reading frame encoding a protein of 442 amino acid residues with a relative Mr of 49,643. The deduced amino acid sequence of human ETB receptor was 88% and 64% identical to those of rat lung ETB receptor and bovine lung ET-1-specific (ETA) receptor, respectively, and contained a relatively long and proline-rich extracellular N-terminal region in addition to a significant similarity with the G protein-coupled receptor super-family with seven transmembrane segments.

Adult↗
PubMed1991

Left ventricular diastolic filling in patients with coronary artery disease without myocardial infarction.

Left ventricular diastolic dysfunction at rest was studied in 24 patients with coronary artery disease but no evidence of previous myocardial infarction. Seven patients with normal coronary arteries were studied as control. Diastolic filling was analyzed by the serial left ventricular volume and 14 radial axes from the gravity point of the left ventricle with cine left ventriculography. There were no differences in the systolic function between coronary artery disease and the normal control. Peak filling rate was decreased significantly in the groups with left anterior descending artery disease (LAD, p less than 0.05) and multivessel disease (MVD, p less than 0.05), but not in the group with right coronary artery disease (RCA). Time to peak filling rate was prolonged in each group of LAD (p less than 0.05), RCA (p less than 0.05), and MVD (p less than 0.001), compared with controls. The time-volume curve showed disturbed rapid filling in the LAD and RCA groups, and also both depressed rapid and slow filling in the MVD group. In the LAD group, the filling fraction was decreased significantly at the time of 25% of the diastolic period (p less than 0.001) and radial distension to the anterior wall was decreased at the time of 25%, 50%, and 75% of the diastolic period, compared with controls. In the RCA group, the filling fraction (p less than 0.001) and radial distension to the posterior wall were decreased only at the time of 25% of the diastolic period. In the MVD group, filling fraction and radial distension to the most wall were decreased at 25%, 50%, and 75% of the diastolic period.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1991

Serial passage of embryonic human astrocytes in serum-free, hormone-supplemented medium.

We applied serum-free cell culture methods that allow extended proliferation of mouse astrocyte precursor cells to the multipassage culture of embryonic human brain cells. Cells were cultured in nutrient medium supplemented with insulin, transferrin, epidermal growth factor, fibroblast growth factor, heparin, high-density lipoprotein, and fibronectin. Cultures were maintained for a maximum of 70 population doublings before proliferation ceased. The cells synthesized glial fibrillary acidic protein, an astrocyte marker, and expression of this protein was increased by incubation of the cells with transforming growth factor beta or serum. These results identify extracellular factors important for proliferation and differentiation of embryonic human astrocytes and provide a controlled system for multipassage culture.

Astrocytes↗
PubMed1991

A molecular genetic linkage map of mouse chromosome 19, including the lpr, Ly-44, and Tdt genes.

The mouse lpr gene, which is an autosomal recessive gene causing autoimmune disease with features of human systemic lupus erythematosus and eventually death from severe immune-complex glomerulonephritis, has been mapped on chromosome 19. To determine its exact chromosomal location, a three-point backcross was carried out by mating (MRL/MpJ-lpr/lpr x MOL-MIT)F1 x MRL/MpJ-lpr/lpr using the genes Ly-44 (lymphocyte differentiation antigen-44) and Tdt (terminal deoxynucleotidyl transferase) as markers. The following order of genes is proposed, with the distances between genes given in parentheses: centromere-Ly-44 (19.3 cM)-lpr (6.1 cM)-Tdt-telomere. The Ly-44a and Tdta alleles are found in all laboratory strains and in the wild Western European subspecies, domesticus and brevirostris. In contrast, the Ly-44b and Tdtb alleles are found in some Asian subspecies, Chinese mice of wild origin, yamashinai and molossinus. Furthermore the third Tdt allele, Tdtc, is detected in castaneus.

Animals↗
PubMed1991

A molecular genetic linkage map of mouse chromosome 18, including spm, Grl-1, Fim-2/c-fms, and Mbp.

Restriction endonuclease fragment length variations (RFLV) were detected in mice with DNA probes for myelin basic protein (Mbp), glucocorticoid receptor-1 (Grl-1), and Friend MuLV integration site-2 (Fim-2). RFLV of the Mbp gene were found in SacI restriction patterns, RFLV of the Grl-1 gene were found in EcoRV patterns, and RFLV of the Fim-2 were found in BglII patterns. A three-point backcross was carried out by the backcross mating (C57BL/KsJ-spm/spm x MOL-MIT)F1 males x C57BL/KsJ-spm/spm; spm is an autosomal recessive gene causing sphingomyelinosis. From the results, spm, Grl-1, Fim-2, and Mbp loci were mapped on chromosome 18, and the following order of genes is proposed, with distances between genes in parentheses: centromere--spm--(7.8 cM)--Grl-1--(7.8 cM)--Fim-2--(39.1 cM)--Mbp--telomere. All laboratory strains and two European subspecies (Mus mus domesticus and M. m. brevirostris) carry the Grl-1a, Fim-2a, and Mbpa alleles. In contrast, another wild subspecies from Europe (M. m. musculus) and some Asian subspecies (M. m. molossinus, Chinese mice of wild origin, and M. m. yamashinai) carry the Grl-1b, Fim-2b, and Mbpb alleles. Only castaneus strains carry the intermediate combination of the Grl-1b, Fim-2a, and Mbpb alleles.

Animals↗
PubMed1991

The diagnostic value of serum pancreatic phospholipase A2 (PLA2) in pancreatic diseases.

The diagnostic significance of serum immunoreactive pancreatic phospholipase A2 (PLA2) was studied in 119 patients with pancreatic disease, 200 with various non-pancreatic disease, and 203 healthy controls using radioimmunoassay (RIA) specific to human pancreatic PLA2. This newly developed RIA using monoclonal antibody was satisfactorily sensitive and reliable. Serum PLA2 was elevated in all six patients with acute pancreatitis. Frequency of abnormal serum PLA2 levels was 60% in chronic pancreatitis (n = 52) and 67% in pancreatic cancer (n = 61). Serum PLA2 levels were low in chronic pancreatitis with severe exocrine insufficiency and advanced pancreatic cancer. In chronic pancreatitis, patients with low serum PLA2 level showed lower enzyme output in secretin test than patients with normal or high serum PLA2 level. Frequency of abnormal PLA2 levels was 27% in non-pancreatic disease and, in particular, patients with renal failure showed high PLA2 levels. Sensitivity (62%) and efficiency (69%) of serum PLA2 assay in pancreatic disease were superior to those of amylase. In conclusion, serum PLA2 determination using RIA was useful for the diagnosis of acute pancreatitis by high serum PLA2 levels and the diagnosis of severe exocrine pancreatic insufficiency by low serum PLA2 levels.

Amylases↗
PubMed1991

Aberrant pancreas is not susceptible to alcoholic pancreatitis.

Three cases of chronic alcoholic pancreatitis associated with aberrant pancreas are reported. All three patients underwent laparotomy, and an aberrant pancreas was found in the jejunum of each of the three patients. Microscopic examination of the aberrant pancreas did not show any changes suggestive of chronic pancreatitis, despite severe chronic pancreatitis in the main pancreas.

Adult↗
PubMed1991

Relations between contractile responses and beta-adrenoceptors in gastric fundus of diabetic rats.

Contractile responses to norepinephrine (NE), and the population of beta-adrenoceptors, were determined in gastric fundus smooth muscle from rats with diabetes induced by streptozotocin (STZ), and age-matched controls. Relaxation and/or contraction of fundus strips of controls and diabetics were induced by 10(-5)M NE. Responses to NE were mainly relaxation in gastric fundus isolated from controls, and contraction in fundus isolated from diabetics. Contraction was blocked by 10(-8) M prazosin and relaxation was blocked by 10(-6) M propranolol. Relaxation by isoproterenol of contraction induced by 10(-6) M acetylcholine was significantly less in fundus from diabetics than in that from controls. The number of beta-adrenoceptors, measured with [125I] iodocyanopindolol as a ligand, was significantly less in gastric fundus membrane isolated from diabetics than in that from controls, but affinity was no different. The level of plasma catecholamine was higher in diabetics than in controls. Results suggest that depression of gastric fundus relaxation and increase of contraction by NE in diabetics could be due to fewer beta-adrenoceptor binding sites caused by down-regulation by higher catecholamine level in diabetic rats.

Animals↗