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Biomedical subjects

H Hayashi

Publications and source records attributed to H Hayashi.

At least 469 records · Page 26Linked to original sources
PubMed1998

An essential role of myosin light-chain kinase in the regulation of agonist- and fluid flow-stimulated Ca2+ influx in endothelial cells.

Cytosolic Ca2+ ([Ca2+]i) plays an important role in endothelial cell signaling. Although it has been suggested that the influx of Ca2+ can be triggered by depletion of intracellular Ca2+ stores, the mechanism (or mechanisms) underlying this phenomenon needs further elaboration. In the present study, involvement of myosin light-chain kinase (MLCK) in the regulation of Ca2+ signaling was investigated in agonist- and fluid flow-stimulated endothelial cells loaded with Ca2+-sensitive dyes. Bradykinin (BK) and thapsigargin caused an increase in [Ca2+]i followed by a sustained rise due to Ca2+ influx from extracellular space and shifted total myosin light-chain (MLC) from the unphosphorylated to the diphosphorylated form. ML-9 (100 microM), an inhibitor of MLCK, abolished Ca2+ influx and prevented MLC diphosphorylation in BK- and thapsigargin-treated cells, but did not affect Ca2+ mobilization from internal stores. Fluid flow stimulation (shear stress=5 dynes/cm2) increased [Ca2+]i and enhanced MLC phosphorylation. ML-9 also inhibited Ca2+ response and MLC phosphorylation in fluid flow-stimulated cells. The Ca2+ influx in response to BK was linearly correlated with the diphosphorylation of MLC in ML-9 treated cells. Effects of ML-5 and ML-7, analogs of ML-9, to inhibit Ca2+ influx paralleled their potencies to inhibit MLCK activity. These findings demonstrate that MLCK plays an essential role in regulating the plasmalemmal Ca2+ influx in agonist- and fluid flow-stimulated endothelial cells. This study is the first to report the close relationship between Ca2+ influx and MLC diphosphorylation.

Animals↗
PubMed1998

Features of early gastric cancer detected by modern diagnostic technique.

To ascertain how the clinicopathologic features of early gastric cancer detected by current diagnostic tools had changed clinical features, we compared 711 early gastric cancer patients with 933 advanced gastric cancer patients regarding age, sex, and tumor location. We found that the proportion of early gastric cancer cases did not change according to age. However, the proportion of early gastric cancer cases in the proximal part was significantly lower than that observed in the distal part (p < 0.01). We conclude that recent diagnostic improvements have rendered age no longer a major deterrent for early detection of gastric cancer. However, a careful examination of the proximal stomach is called for because it is so hard to detect small lesions in that area.

Adult↗
PubMed1998

Different effects of class Ic and III antiarrhythmic drugs on vagotonic atrial fibrillation in the canine heart.

Effects of class Ic drug pilsicainide and class III drug MS-551 were determined in the canine model of atrial fibrillation (AF) induced under vagal stimulation. Pilsicainide injected intravenously at a dose of 1.0 mg/kg over 3 min terminated AF in six of six dogs. After pilsicainide injection, the effective refractory period (ERP) of the right atrium (RA) increased (104 +/- 22 to 122 +/- 31 ms; p < 0.05), and intraatrial conduction time (CT) increased (24%; p < 0.05) in the RA during vagal stimulation. Wavelength index (WLI; ERP/CT), an estimate of the wavelength for reentry, was decreased slightly but significantly (-2%; p < 0.05) in the RA after pilsicainide. MS-551 injected intravenously at a dose of 0.5 mg/kg over a 3-min period terminated AF in three of eight dogs. An additional dose of 0.5 mg/kg of MS-551 terminated AF in three of the remaining five dogs. After MS-551 injection, ERP increased (100 +/- 30 to 143 +/- 28 ms; p < 0.05), but CT remained unchanged in the RA, and therefore WLI was increased significantly (48%; p < 0.01). Immediately before termination of AF with test drugs, mean AF intervals (FF intervals) increased, whereas the standard deviation of FF intervals did not change significantly. In conclusion, both pilsicainide and MS-551 effectively terminated vagotonic AF after an increase in FF intervals. However, changes in WLI were different between the two test drugs. Vagotonic AF could, therefore, be terminated either by prolongation of ERP or suppression of conduction with antiarrhythmic drugs.

Animals↗
PubMed1998

Effect of GR144053, a fibrinogen-receptor antagonist, on thrombus formation and vascular patency after thrombolysis by tPA in the injured carotid artery of the hamster.

The antithrombotic effect of GR144053, which inhibits platelet aggregation by binding to the fibrinogen receptor (glycoprotein IIb/IIIa), was investigated in vitro and in vivo by using hamsters. This compound inhibited the platelet aggregation induced by adenosine diphosphate (ADP; 2.5 microM) with a mean inhibitory concentration (IC50) value of 2.2 +/- 0.4 x 10(-5) M. Vascular injury was inflicted in one carotid artery by using a modified catheter to produce endothelial denudation. In the control group, arterial blood flow was interrupted 4.4 +/- 2.3 min (n = 12) after the injury. When GR144053 continuously infused intravenously at doses of 0 (saline) 0.1, 0.3, and 1.0 mg/kg/h (n = 8, each), the time that elapsed before the vessel became completely obstructed was prolonged in a dose-dependent manner. In separate experiments, reperfusion could be obtained by continuous infusion of tissue-type plasminogen activator (tPA; 0.52 mg/kg) starting 30 min after the initiation of thrombus formation. When GR144053 (0.3 and 1.0 mg/kg/h) was infused in addition to tPA, the incidence of reperfusion and the later patency of the reperfused artery were much improved as compared with tPA alone. The bleeding time at the end of tPA infusion was significantly prolonged in the presence of the highest dose of GR144053. Next, neointima formation was evaluated 2 weeks after the vascular injury. When GR144053 (0.3 mg/kg/h) was continuously infused i.v. by an implanted osmotic pump for 14 days, the neointimal area was significantly reduced. In separate hamsters, the proliferating index of smooth muscle cells (SMCs) by using bromodeoxyuridine (BrdU) was investigated, and treatment with both tPA and GR144053 significantly decreased the SMC proliferation index in vivo. However, in the in vitro experiments using a hamster SMC line, GR144053 did not have an inhibitory effect on SMC proliferation. These findings suggest that GR144053 inhibits platelet activation on the injured artery and improves vascular patency after thrombolysis with tPA, which furthermore results in suppression of neointima formation.

Animals↗
PubMed1998

Vitrectomy for diabetic retinopathy in patients undergoing hemodialysis for associated end-stage renal failure.

PURPOSE: Candidates for diabetic vitrectomy often have concurrent renal dysfunction and have undergone hemodialysis. The influence of hemodialysis on the surgical outcome of vitrectomy was investigated. METHODS: Vitrectomy was performed on 76 eyes with proliferative diabetic retinopathy in 66 patients with end-stage renal failure who had undergone hemodialysis. Follow-up was longer than 1 year. RESULTS: No uncontrollable hemorrhage occurred either during or immediately after the surgery. Final visual acuity after surgery was the same as preoperative visual acuity in 31.5% of the eyes; improvement was seen in 60.5% of the eyes. A final visual acuity of 0.2 or better was observed in 57.6% of the eyes. Major postoperative complications included recurrent vitreous hemorrhage, rhegmatogenous retinal detachment, fibrin clot formation, neovascular glaucoma, flat anterior chamber, and a transient rise in intraocular pressure. CONCLUSION: Renal failure and hemodialysis do not appear to have a deteriorative influence on the outcome of vitrectomy for proliferative diabetic retinopathy. A flat anterior chamber seems to be a rare and perhaps unique postoperative complication of gas-filled eyes in patients who have undergone hemodialysis.

Diabetic Retinopathy↗
PubMed1998

Inhibition of enhanced toxin production by Clostridium difficile in biotin-limited conditions.

Production of toxins A and B by Clostridium difficile is enhanced in a defined medium with biotin-limited conditions. In the present study compounds inhibitory to enhanced toxin production by a C. difficile strain were examined. Increases in biotin concentration from 0.05 nM to 50 nM accelerated growth and inhibited enhanced toxin production. Asparagine, glutamic acid and glutamine (10 mM) showed an effect on growth and toxin production similar to that of biotin. Lysine (10 mM) suppressed growth and inhibited toxin production. Addition of these toxin-inhibitory compounds within an incubation period of 2 days inhibited the enhanced toxin production, but later addition showed only slight inhibition of toxin production. Amino acids contained in the defined medium under the biotin-limited conditions were actively utilised in the presence of the three toxin-inhibitory amino acids, but in the presence of lysine, amino-acid utilisation was suppressed. Different mechanisms of action of these toxin-inhibitory molecules, which may be divided into excess biotin, asparagine-glutamic acid-glutamine group, and lysine, are discussed.

Amino Acids↗
PubMed1998

High rate of induction of human autologous cytotoxic T lymphocytes against renal carcinoma cells cultured with an interleukin cocktail.

A high rate of induction (9 of 10 cases) of human autologous cytotoxic T lymphocytes (CTL) was achieved in vitro from peripheral blood mononuclear cells of renal carcinoma patients by applying an interleukin (IL)-cocktail consisting of IL-1, -2, -4, and -6. The CTL specifically lysed their own target carcinoma cells within 24 h but did not kill neighboring autologous normal kidney cells or allogeneic renal cancer cell lines. In the case of TUHR4TKB, for which autologous CTL were not induced, no expression of MHC class-I molecules was observed on the surface of these carcinoma cells, although they were sensitive to autologous natural killer cells. The results imply that adoptive immunotherapy for metastasized renal carcinoma will be feasible with autologous CTL in combination with natural killer cells.

Cell Survival↗
PubMed1998

Cryoglobulinaemia among maintenance haemodialysis patients and its relation to hepatitis C infection.

It has been shown that hepatitis C virus (HCV) infection is closely associated with mixed type cryoglobulinaemia. It is also known that HCV infection is rampant among chronic haemodialysis patients. We studied 531 renal failure patients on maintenance dialysis including 170 with positive HCV antibodies for cryoglobulinaemia, and its incidence was compared with controls which consisted of 242 chronic hepatitis C patients without renal failure and 183 healthy adults. Cryoglobulinaemia was present in 30.6% of dialysis patients with HCV infection, 10.8% of dialysis patients without HCV infection, 29.8% of patients with chronic hepatitis C without renal failure, and 0% of healthy adults. Among the 30 new renal failure patients who were started on dialysis within 6 months, four were positive for HCV antibodies, and one of them had cryoglobulinaemia; of the 26 HCV-negative patients, four (15%) were cryoglobulinaemic. The cryocrit values among dialysis patients were much lower than those of the control cases and other reports on non-dialysis cases. Patients with cryoglobulinaemia were generally younger compared with patients negative for this condition. There was no correlation between cryoglobulinaemia and past blood transfusion, underlying disease or length of dialysis. Cryoglobulinaemic patients seem to develop renal failure at relatively young ages and a considerable proportion of cryoglobulinaemic dialysis patients may have already had cryoglobulinaemia at the time of the start of haemodialysis. There was no indication that the presence of cryoglobulin in serum adversely affects the liver disease nor increases serum virus load in HCV-infected dialysis patients. Thus, it was concluded that although HCV infection has a certain role in the development of cryoglobulinaemia in dialysis patients, they develop cryoglobulinaemia less frequently and produce cryoglobulin to a lesser degree in the presence of HCV infection as compared with non-dialysis patients.

Adult↗
PubMed1998

Acute hepatitis C among renal failure patients on chronic haemodialysis.

Hepatitis C virus (HCV) infection is common in haemodialysis units, yet little information is available about the clinical feature of acute hepatitis C among renal failure patients. The present study is based on 49 cases of acute hepatitis C seen at a haemodialysis centre where sporadic nosocomial infection was occurring up to June 1993. Liver function tests were done at 4 weekly intervals on all dialysis patients, anti-HCV antibodies were tested by the C-100 and second generation tests and serum HCV-RNA was determined by the branched DNA and Amplicore tests. Diagnosis of acute hepatitis C was made on the basis of an acute rise in alanine aminotransferase (ALT) and seroconversion to positive anti-HCV antibodies. Clinical presentation of acute hepatitis was generally mild with rare overt jaundice and the diagnosis was possible only from increased ALT, which was generally low. Spontaneous resolution of acute hepatitis within 8 months with clearance of viral RNA occurred in only four cases, 91.8% of patients developing chronic hepatitis. Biopsy in 12 cases with high ALT levels showed mild to moderate inflammatory activities. In conclusion, the clinical presentation of acute hepatitis C is generally mild in chronic haemodialysis patients, but spontaneous resolution is infrequent. A longer follow-up period is required for defining the long-term prognosis.

Acute Disease↗
PubMed1998

Anterior capsule contraction and intraocular lens dislocation in eyes with pseudoexfoliation syndrome.

AIMS: To examine the extent of anterior capsule contraction as well as intraocular lens (IOL) decentration and tilt following implant surgery in eyes with pseudoexfoliation syndrome (PE). METHODS: 53 eyes from 53 patients with PE and 53 control eyes from 53 age matched patients, undergoing phacoemulsification and implant surgery, were recruited. The anterior capsule opening area and the amounts of IOL decentration and tilt after undergoing continuous curvilinear capsulorhexis were measured using the Scheimpflug videophotography system at 1 week and 1, 3, 6, 9, and 12 months postoperatively. RESULTS: The mean area of the anterior capsule opening in the PE group was significantly smaller than that in the control group at 1 month postoperatively and later. The percentage reductions in the PE group were approximately 25%, while they were less than 10% in the control group. The degree of IOL tilt was also larger in the PE group than in the control group. Five eyes (9.4%) in the PE group underwent a neodymium: YAG laser anterior capsulotomy, but none in the control group underwent a capsulotomy. CONCLUSIONS: The contraction of the anterior capsule opening was more extensive in the PE eyes than in the control eyes, thus resulting in a high Nd:YAG laser anterior capsulotomy rate. The IOL tilt was also greater in the PE eyes than in the control eyes.

Aged↗
PubMed1998

Comparison of decentration and tilt between one piece and three piece polymethyl methacrylate intraocular lenses.

BACKGROUND: The extent of the decentration and tilt was prospectively compared between one piece polymethyl methacrylate (PMMA) and three piece PMMA intraocular lenses (IOLs) which were implanted in the capsular bag after performing continuous curvilinear capsulorhexis. METHODS: 91 patients underwent a one piece PMMA IOL implantation in one eye as well as the implantation of the three piece PMMA IOL with polyvinylidene fluoride loops in the opposite eye. The length of the lens decentration and the angle of the tilt were quantitated using the anterior eye segment analysis system (EAS-1000) at 1 week as well as 1, 3, and 6 months postoperatively. RESULTS: The mean length of the decentration in the one piece IOL was smaller than that in the three piece IOL at 1 week (p = 0.0092), 1 month (p = 0.0044), 3 months (p = 0.0069), and 6 months (p = 0.0010) postoperatively. However, no significant difference was found in the degree of the tilt between the two types of IOLs throughout the observation periods. CONCLUSION: These results clarified that the one piece PMMA IOL with rigid PMMA haptics implanted in the capsular bag provides a better centration than the three piece PMMA IOL with flexible haptics, whereas the tilt was the same between the two types of IOLs.

Aged↗
PubMed1998

Impact of preoperative serum carcinoembryonic antigen, CA 19-9 and alpha fetoprotein levels in gastric cancer patients.

The relationship between preoperative serum carcinoembryonic antigen (CEA), CA 19-9 and alpha-fetoprotein (AFP) levels and their clinicopathological features were evaluated in gastric cancer patients. The positive rates of CEA, CA 19-9 and AFP were 24.8, 27.6 and 12.7%, respectively. Gastric cancer with deeper tumor invasion was significantly more common among patients positive for these tumor markers. Patients with positive CEA or CA 19-9 values had a significantly high risk of lymph node metastases (p = 0.045 and p = 0.002, respectively). Synchronous liver metastases was more commonly found in patients with a positive CA 19-9 value. A significant difference (p < 0.001) in survival rate was found between patients with positive CA 19-9 values and those with negative values. CA 19-9 is useful for the prognosis of gastric cancer patients, whereas CEA, although unsuitable for prognosis, contributes to the prediction of cancer invasion.

Adult↗
PubMed1998

Staged reperfusion preserves the coronary flow reserve, especially in the regions not severely damaged by ischemic injury in the canine heart.

The objective of this study was to determine the effects of staged reperfusion on the progressive reduction in coronary blood flow (CBF) and coronary flow reserve during reperfusion and on the infarct size in the canine heart. Fifteen dogs underwent 90 min of left circumflex coronary artery occlusion and 3 hr of reperfusion. In the abrupt reperfusion group, the occluder was released completely at the initiation of reperfusion. In the staged reperfusion group, CBF was maintained at 20% of preocclusion values for 10 min after initiation of reperfusion, then gradually released, and completely released 20 min after initiation of reperfusion. There was no significant difference in CBF between the staged (n = seven) and abrupt (n = eight) groups after 3 hr of reperfusion. The repayment of flow debt in the staged reperfusion group was significantly greater than in the abrupt reperfusion group after 3 hr of reperfusion (260+/-120% vs 100+/-60%, staged vs abrupt at 3 hr, p < 0.03). The ratio of peak reactive hyperemic flow to resting flow in the staged reperfusion group was significantly greater than in the abrupt reperfusion group throughout the reperfusion phase (4.4+/-1.0 vs 2.6+/-0.6 at 3 hr, p < 0.001), and had returned to the preocclusion values after 3 hr of reperfusion. This preservation of the coronary flow reserve in the staged reperfusion group was observed in the epicardium (4.1+/-0.6 vs 2.8+/-0.7, staged vs abrupt at 3 hr, p < 0.01), but not in the endocardium or midmyocardium. Infarct size did not differ significantly between the two groups. Staged reperfusion in this study did not appear to attenuate the reduction of CBF, or to reduce infarct size, however preserved the coronary flow reserve, especially in the regions not severely damaged by ischemic injury.

Animals↗
PubMed1998

Comparison of the effects of gemfibrozil and clofibric acid on peroxisomal enzymes and cholesterol synthesis of rat hepatocytes.

We studied whether the peroxisomal proliferation, induction of 3-hydroxy-3-methylglutaryl-CoA reductase (HMG-CoA reductase) and activation of cholesterol synthesis by gemfibrozil shown in whole body (Hashimoto F., Ishikawa T., Hamada S. and Hayashi H., Biochemical. Pharm., 49, 1213-1221 (1995)) is also detected at a culture cell level, and we made a comparative analysis of the effects of clofibric acid. Gemfibrozil at 0.25 mM increased the activity of some peroxisomal enzymes (catalase and the cyanide-insensitive fatty acyl-CoA oxidizing system) after incubation for 72 h. However, contrary to whole body experiments, gemfibrozil decreased the activity of HMG-CoA reductase and cholesterol synthesis from [14C]acetate. At 1 mM, gemfibrozil decreased not only the activity of HMG-CoA reductase and cholesterol synthesis, but also the protein content of the cells and peroxisomal enzyme activity, indicating nonspecific inhibition at this concentration. Clofibric acid (0.25 and 1 mM) increased the activity of peroxisomal enzymes, but decreased the activity of HMG-CoA reductase and cholesterol synthesis. With respect to the direct effect on HMG-CoA reductase in the cell homogenate, gemfibrozil at 0.25 mm did not affect the activity, but it clearly inhibited the activity at 2 mM and above. Clofibric acid at 2 mM hardly affected the activity, but it clearly decreased the activity at 5 mM and over. That is, gemfibrozil directly inhibited the activity more strongly than clofibric acid. The direct inhibition of the enzyme itself required higher concentrations of both agents than did inhibition at the culture cell level. These results suggest that the cytotoxicity of gemfibrozil is greater than that of clofibric acid, and that gemfibrozil, as well as clofibric acid, can induce peroxisomal enzymes in the culture cell level. In contrast to whole body results, gemfibrozil may suppress cholesterol synthesis from [14C]acetate through the inhibition of HMG-CoA reductase at the culture cell level. The decreases in the reductase activity caused by gemfibrozil and clofibric acid at the culture cell level may not be caused by the direct inhibition of the enzyme.

Animals↗
PubMed1998

Phylogenetic relationship of Glycyrrhiza plants based on rbcL sequences.

The nucleotide sequences of the ribulose-1,5-bisphosphate carboxylase/oxygenase large subunit gene (rbcL) of Glycyrrhiza glabra, G. uralensis, G. inflata, G. echinata, and G. pallidiflora have been determined to construct the phylogenetic tree. In the phylogenetic tree based on the rbcL sequences, the five Glycyrrhiza species were divided into two groups: the three glycyrrhizin-producing species G. glabra, G. uralensis, and G. inflata; and the two glycyrrhizin-nonproducing species G. echinata and G. pallidiflora. Among the three glycyrrhizin-producing species, only two nucleotide substitutions were observed between the rbcL sequence of G. glabra and G. uralensis, and the sequence of G. uralensis was identical to that of G. inflata, indicating that the three glycyrrhizin-producing species are closely related.

DNA, Plant↗
PubMed1998

Seasonal variation of glycyrrhizin and isoliquiritigenin glycosides in the root of Glycyrrhiza glabra L.

The time courses of the glycyrrhizin and isoliquiritigenin glycoside contents in the thickening roots of licorice, Glycyrrhiza glabra L., have been determined. The glycyrrhizin content in 1-year-old roots rapidly increased from October to November, whereas the isoliquiritigenin glycoside content increased up to October. In 3-year-old plants, although the isoliquiritigenin glycoside content rapidly increased from June to July, the glycyrrhizin content did not show any significant increase from May to August. The glycyrrhizin content increased during the senescence of the aerial parts as well as during the early stage of shoot elongation. The incorporation of [14C]mevalonic acid into the glycyrrhizin fraction by the root segments was high in May, June and September, and low in August and winter. These results indicated that the biosynthesis of glycyrrhizin is differently regulated from that of isoliquiritigenin glycoside in the thickening root of G. glabra.

Carbon Radioisotopes↗