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Biomedical subjects

Y Hara

Publications and source records attributed to Y Hara.

At least 325 records · Page 18Linked to original sources
PubMed1996

Endothelin-1 partially inhibits ATP-sensitive K+ current in guinea pig ventricular cells.

To clarify the pathophysiological significance of endothelin (ET) in the ischemic myocardium, we examined the effect of endothelin-1 (ET-1) on the ATP-sensitive K+ current (IK.ATP) and compared it with that of ET-3 in guinea pig ventricular cells using conventional microelectrode and patch clamp techniques. In isolated guinea pig papillary muscles, ET-1 (30 nM) markedly increased developed tension (DT), with little influence on action potential duration (APD), whereas ET-3 at the same concentration failed to affect DT or APD. Both nicorandil (1 mM) and cromakalim (30 microM) markedly shortened APD and decreased DT in papillary muscles. ET-1, but not ET-3, partially reversed the nicorandil-induced decreases in APD and DT in a concentration-dependent manner. ET-1 also attenuated the cromakalim-induced decreases in APD and DT. In single ventricular myocytes, both nicorandil and cromakalim increased a steady-state outward current, which was sensitive to 1 microM glibenclamide, suggesting that these drugs activate IK.ATP. ET-1 (30 nM) significantly inhibited the IK.ATP, whereas ET-3 failed to affect it. The ET-1 induced inhibition of IK.ATP was abolished by BQ-485 (100 nM), an ETA receptor-selective antagonist. Neither the protein kinase C (PKC) inhibitor staurosporine (20 nM) nor the calmodulin antagonist W-7 (50 microM) affected the inhibitory action of ET-1 on the nicorandil-induced IK.ATP. In pertussis toxin (PTX)-treated cells, the inhibitory action of ET-1 on IK.ATP was augmented rather than attenuated. These results suggest that ET-1 partially inhibits the IK.ATP through the activation of ETA receptors, although the precise intracellular mechanism remains to be clarified. Because activation of the ATP-sensitive K+ channels is considered to protect the ischemic myocardium, the partial inhibition of IK.ATP by ET-1 may lead to the aggravation of myocardial injury, potentially due to an increase in transmembrane Ca2+ influx.

Action Potentials↗
PubMed1996

alpha 1-Adrenoceptor stimulation partially inhibits ATP-sensitive K+ current in guinea pig ventricular cells: attenuation of the action potential shortening induced by hypoxia and K+ channel openers.

Effects of alpha 1-adrenoceptor stimulation on the action potential shortening produced by K+ channel openers (KCOs) or hypoxia and on the ATP-sensitive K+ current (IK.ATP) activated by KCOs were examined in guinea-pig ventricular cells by using conventional microelectrode and patch-clamp techniques. In papillary muscles, nicorandil (1 mM) or cromakalim (30 microM) markedly shortened the action potential duration (APD) (to 51 +/- 2% and 40 +/- 5% of each control value). Addition of 100 microM methoxamine, an alpha 1-adrenoceptor agonist, partially but significantly reversed the KCOs-induced APD shortening (to 69 +/- 3% and 50 +/- 4% of each control value). The APD-prolonging effect of methoxamine was antagonized by 1 microM prazosin (alpha 1-antagonist) and 100 nM WB4101 (alpha 1A-antagonist) but not by 10 microM chloroethylclonidine (alpha 1B-antagonist). In papillary muscles exposed to a hypoxic, glucose-free solution, APD declined gradually. In the presence of 100 microM methoxamine or 10 microM glibenclamide, the hypoxia-induced action potential shortening was significantly inhibited. In single ventricular myocytes, the KCOs increased a steady-state outward current that was abolished by glibenclamide (1 microM), thereby suggesting that these KCOs activate IK.ATP. Methoxamine (100 microM) significantly inhibited the nicorandil-induced IK.ATP by 18 +/- 5% and the cromakalim-induced IK.ATP by 16 +/- 2%. 4 beta-Phorbol 12-myristate 13-acetate (100 nM), a protein kinase C activator, failed to mimic the alpha 1-adrenoceptor-mediated inhibition of the nicorandil-induced outward current. Staurosporine (30 nM), a protein kinase C inhibitor, also failed to affect the partial inhibition of IK.ATP by methoxamine. Neither intracellular loading of heparin (100 micrograms/ml), an inositol 1,4,5-trisphosphate (IP3)-dependent Ca2+ release inhibitor, nor IP3 (20 microM) plus inositol 1,3,4,5-tetrakisphosphate (IP4 5 microM) could affect the inhibitory action of methoxamine. In conclusion, alpha 1A-adrenergic stimulation partially inhibits IK.ATP in cardiac cells. Neither protein kinase C activation nor IP3 formation appears to be involved in the partial inhibition of IK.ATP. The alpha 1A-adrenoceptor-mediated inhibition of IK.ATP may be deleterious for ischemic myocardium and partly offset the cardioprotective effect of KCOs because attenuation of action potential shortening may potentially increase Ca2+ influx in ischemic cells.

Action Potentials↗
PubMed1996

Inhibitory effects of tea catechins, black tea extract and oolong tea extract on hepatocarcinogenesis in rat.

Inhibitory effects of individual tea catechins ((--)-epicatechin, (--)-epigallocatechin, (--)-epicatechin gallate, (--)-epigallocatechin gallate), black tea extract and oolong tea extract on hepatocarcinogenesis were investigated. Male F344 rats received a single dose of diethylnitrosamine (200 mg/kg, i.p.), and thereafter phenobarbital (0.05%) was administered in the drinking water for a period of 6 weeks. Tea catechins, black tea extract or oolong tea extract were given during the entire experimental period, during only the initiation period or during only the promotion period. All four tea catechins, black tea extract and oolong tea extract (0.05 or 0.1%) significantly decreased the number and area of preneoplastic glutathione S-transferase placental form-positive foci in the liver. These results suggest that tea catechins, black tea extract and oolong tea extract have a chemopreventive action against hepatocarcinogenesis.

Animals↗
PubMed1996

Thermoregulatory response in female patients during lower abdominal surgery in the head-down tilt position.

BACKGROUND: The head-down tilt (HDT) position suppresses sympathetic nervous activity. We investigated the effect on thermoregulation of the HDT position during lower abdominal surgery under general anaesthesia. METHODS: Tympanic membrane temperature was measured to assess core temperature, and forearm-fingertip and calf-toe temperature gradients were used to assess peripheral vasoconstriction in 30 female patients less than 60 years of age. RESULTS: During surgery in the HDT position (n = 10), the tympanic membrane temperature was similar to that of patients in the supine position (n = 10) (36.2 degrees C and 36.2 degrees C), but in patients operated in the HDT position and premedicated with an angiotensin converting enzyme inhibitor (5 mg of enalapril, n = 10) it was reduced (35.7 degrees C, P < 0.05). In both groups of patients operated in the HDT position, forearm and calf skin-surface temperature gradients were lower by 2.3 degrees C than those in patients operated in the supine position (P < 0.05). CONCLUSIONS: During lower abdominal surgery the head-down tilt position does not augment core hypothermia in spite of suppressed peripheral vasoconstriction, and the renin-angiotensin system may be of importance for thermoregulation.

Adult↗
PubMed1996

Case report: mucin-producing cystic neoplasm of the pancreas with onset in childhood.

Mucin-producing tumours of the pancreas have been recently reported with increasing frequency and most cases have occurred in middle-aged and elderly people. In the present report, a case of a 21-year-old man with mucinous cystadenoma of the pancreas is reported. He had a long history of recurrent pancreatitis from the age of 8. When he was aged 10, the first branch of the main pancreatic duct was shown to be enlarged on endoscopic retrograde pancreaticography (ERP). A series of ERP studies and computed tomography scans performed over a period of 11 years demonstrated continuing growth of this enlargement of the pancreatic duct. Pancreaticoduodenectomy was performed and the patient has been well without further episodes of acute pancreatitis and has been free of recurrent tumour for 1 year.

Adult↗
PubMed1996

Isolation of alkaline phosphatase-positive gingival fibroblasts from patients with chronic inflammatory periodontal disease.

We have reported recently that increased expression of membrane alkaline phosphatase (ALP) activity is a phenotypical characteristic of gingival fibroblasts located in chronic inflammatory periodontal lesions. To understand the cellular properties of these cells, we isolated ALP-positive gingival fibroblasts from patients with adult periodontitis and evaluated their proliferative potential. Using an enzymatic digestion procedure, we prepared gingival cell suspensions containing ALP-positive fibroblasts without affecting their ALP activities. These cell suspensions were then subjected to 1 g sedimentation, followed by allowing cells to adhere to substrata. Using this procedure, 71.9% of isolated cells were ALP-positive. Dissociation of ALP-positive fibroblasts and contamination by non-fibroblastic cells were examined by cytochemical and immunocytochemical analyses. The proliferative capacity of ALP-positive fibroblasts in culture was assessed by monitoring the proportion of ALP-positive cells after repeated subculture passages and by labelling DNA-synthesizing cells with bromodeoxyuridine (BrdU). The proportion of ALP-positive fibroblasts decreased during cell culture passages without an apparent change in the ALP-positive phenotype. The percentage of BrdU-positive cells was significantly lower among ALP-positive than among ALP-negative fibroblasts. These results indicate that ALP-positive fibroblasts in chronic inflammatory periodontal lesions have low growth potential. We suggest that their reduced capacity to grow in vitro reflects a more differentiated state induced under inflammatory conditions in vivo.

Adult↗
PubMed1996

Effects of T cell adoptive transfer into nude mice on alveolar bone resorption induced by endotoxin.

Using the method of reconstitution of nude mice with T cells, we examined the effects of T cell on alveolar bone resorption induced by repeated injections of Escherichia coli endotoxin into periodontal tissue. Three mice groups (normal, nude and T cell reconstituted nude mice) were used. Endotoxin derived from E coli was repeatedly injected into the gingiva of the mice left mandibles every 48 h and the mice were killed on the day after the 1st, 4th, 7th, 10th, 13th and 20th injections of endotoxin. Alveolar bone resorption was examined histopathologically and histomorphometrically. Bone surfaces in contact with the osteoclast were defined as the site of active resorption and the ratios of active resorption were compared among the 3 mice groups. Consequently, no active resorption was found after the first injection of endotoxin in any group. After the 4th injection, active resorption was found in normal mice and T cell reconstituted nude mice and gradually rose with the increase in the injection frequency. In contrast, few osteoclasts were found even after the 10th injection in the nude mice. In addition, there were statistically significant differences between the normal mice and nude mice after the 4th and 10th injections (p < 0.05). These findings suggested that T cell influences periodontal bone destruction induced by local administration of endotoxin during the early phases.

Adoptive Transfer↗
PubMed1996

Serum rheumatoid factor induced by intraperitoneal administration of periodontopathic bacterial lipopolysaccharide in mice.

Serum rheumatoid factor (RF) level and peritoneal and splenic CD5+B (B-1) cells in mice were examined after intraperitoneal administration of purified lipopoly-saccharides (LPS) from oral periodontopathic bacteria; Porphyromonas gingivalis, Actinobacillus actinomycetemcomitans, Fusobacterium nucleatum and Capnocytophaga ochracea. F. nucleatum and C. ochracea LPS induced higher levels of serum IgM- and IgG-RF, while P. gingivalis LPS showed the least induction. In addition, wet weights of spleen and serum IgM and IgG concentration were markedly increased in F. nucleatum LPS injected group. On the other hand, the proportion of CD5+ B cells to lymphocytes in the peritoneal cavity and spleen did not increase. The reason for this was not clear but conventional B cells (CD5- B cells) might increase more rapidly with splenic enlargement than CD5+ B cells. These results suggested that RF induced by bacterial LPS may modulate immune responses against bacteria and plays an important role for defence and destruction of periodontal tissue.

Aggregatibacter actinomycetemcomitans↗
PubMed1996

Cloning and expression of a putative alcohol dehydrogenase gene of Entamoeba histolytica and its application to immunological examination.

To clone and express the genes encoding major antigens of Entamoeba histolytica, we constructed a lambda gt11 cDNA library for E. histolytica HM1:IMSS and screened it with pooled sera from patients with amoebiasis. A 1,223-bp cDNA was cloned (clone 1223), and its nucleotide sequence was determined. The amino acid sequence predicted to be encoded by the open reading frame of clone 1223 consisted of 396 residues and showed 32.5 and 32.3% homology to the NADH-dependent butanol dehydrogenases I and II (bdhA and bdhB) of Clostridium acetobutylicum, respectively. In addition, 29 of the 34 consensus positions of bdhA and bdhB were also well conserved in clone 1223. The recombinant protein expressed from clone 1223 had an estimated molecular mass of 43.5 kDa as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The antigenicity and specificity of the recombinant protein were evaluated by an enzyme-linked immunosorbent assay using sera obtained from two clinical groups of patients with amoebiasis and a group of healthy controls. The recombinant protein had potent and specific antigenicity. In all, 53 serum samples (88.3%) from 60 patients with amoebiasis were positive for immunoglobulin G antibody against the recombinant protein, with a mean optical density value of 0.42. In contrast, 53 of 54 healthy control serum samples were negative, with only 1 positive serum sample showing the lower optical density value. These results suggested that clone 1223 is promising in terms of providing a useful antigen for the accurate serodiagnosis of amoebiasis and that the gene encodes a putative alcohol dehydrogenase of E. histolytica.

Alcohol Dehydrogenase↗
PubMed1996

Insulin resistance as an independent risk factor for carotid wall thickening.

It has been reported that insulin resistance is associated with essential hypertension and that an aggregation of risk factors-hypertension, dyslipidemia, and glucose intolerance-together with insulin resistance leads to the more frequent appearance of coronary artery disease. We examined the relation between early asymptomatic atherosclerosis and these risk factors in 72 nondiabetic subjects with essential hypertension (41 men, 31 women) aged 50 to 59 years. Intima-media thickness and plaque formation of the carotid artery were assessed by B-mode ultrasonography, and insulin sensitivity was measured by the steady-state plasma glucose method. Lipoprotein profile was analyzed by ultracentrifugation. The intima-media thickness of the common carotid artery significantly correlated with systolic pressure; mean blood pressure; steady-state plasma glucose, indicating insulin resistance; fasting insulin; area under the curve of plasma insulin and glucose; body mass index; apolipoprotein B; apolipoprotein B in low-density lipoprotein; lower ratio of cholesterol to apolipoprotein B of low-density lipoprotein; and decreased high-density lipoprotein cholesterol. By multiple regression analysis, steady-state plasma glucose was the strongest risk, followed by lower high-density lipoprotein and systolic pressure. These three factors accounted for 54.9% of all the risk for increased intima-media thickness of the common carotid artery. In conclusion, insulin resistance was the strongest risk factor for carotid intima-media thickness, followed by lower high-density lipoprotein cholesterol and hypertension. An effort to maintain normal insulin sensitivity is essential for the prevention of early atheromatous lesions in essential hypertension.

Arteriosclerosis↗
PubMed1996

Absorption of tea catechins into rat portal vein.

Following the oral administration of tea catechins, (-)-epicatechin, (-)-epigallocatechin, (-)-epicatechin gallate and (-)-epigallocatechin gallate, respectively, to rats, the presence of these catechins in the portal blood was examined. It was confirmed by HPLC and mass spectrometry analysis that each of the administered catechins was present in the blood. These results clearly indicate that four predominant catechins in fresh tea leaves are absorbed, at least in part, into the rat portal vein.

Absorption↗
PubMed1996

Clinical impact of insulin resistance syndrome in cardiovascular diseases and its therapeutic approach.

In subjects with coronary artery diseases (obstructive and vasospastic angina pectoris (AP)) who have no diabetes, hypertension, obesity and physical inactivity, insulin sensitivity was significantly reduced with compensated hyperinsulinemia on OGTT. Insulin resistance significantly correlated with coronary atherosclerosis score. In vasospastic AP (VAP), those who fulfilled more than 3 risk factors out of 5 (hyperinsulinemia, obesity, glucose intolerance, hypertension, dyslipidemia) consist of 70 and 40% for smokers and nonsmokers respectively. Insulin resistance syndrome who fulfilled all the criteria was 9-10% for VAP. In atherothrombotic brain infarction (ATTI) with the same exclusion criteria, the similar insulin resistance and hyperinsulinemia have been observed, but not in embolic (cardiac origin) or lacunar infarction. In ATTI, high TG and apo B with low HDL-chol were noted in blood. In essential hypertension without diabetes and obesity, hyperinsulinemia was noted in 25-35% and insulin resistance in 56-88%. Reduction of blood pressure with alpha blocker (bunazosin), ACE inhibitor (cilazapril), long-acting Ca++ blocker (amlodipine) significantly improved lowered insulin sensitivity. Insulin resistance rather than hyperinsulinemia is more closely associated with blood pressure. Cardiovascular diseases (vasospastic and obstructive AP, brain cortical artery diseases) are prone to develop diabetes because of insulin resistance and also promote the generation of cumulative risk factors resulting in a vicious cycle. Efforts to alleviate insulin resistance is crucial for the primary and secondary prevention of cardiovascular diseases.

Adrenergic alpha-Antagonists↗
PubMed1996

Quantitative and qualitative derangement of apolipoprotein B-containing lipoproteins as a risk factor for diabetic macroangiopathy in nonobese NIDDM subjects.

Cholesterol, triglyceride (TG), and apolipoprotein (apo) B were determined in plasma and in lipoprotein subfractions (VLDL, intermediate-density lipoproteins [IDL], LDL, and HDL) in nonobese NIDDM subjects, who were classified into well-controlled, fairly controlled, or poorly controlled states with or without macrovascular complications (macroangiopathy [MA]). The same analyses were also performed on subjects who had coronary artery disease (CAD) with stable angina pectoris (SA) or unstable angina pectoris (UA) and acute myocardial infarction, cerebrovascular disease (CVD) with atherothrombotic or lacunar infarction, and arteriosclerosis obliterans (ASO). In nonobese NIDDM subjects, the number of apoB-containing lipoproteins (VLDL, IDL, and LDL) increased. This alteration was more prominent in subjects with poorly or fairly controlled disease as well as in subjects with MA, but not in those with well-controlled NIDDM. Cholesterol/apoB in LDL decreased in subjects with poorly or fairly controlled diabetes or with MA and was correlated with low HDL cholesterol. The disorder is characterized by hyperbetalipoproteinemia with elevated LDL cholesterol and small dense LDL. In obese NIDDM subjects, the similar disorder was more pronounced. Glycemic control had less effect and hyperinsulinemia, if present, aggravated the lipid disorder. In those with CAD, the number of IDLs increased and the LDL fraction had the properties of small dense LDL. HDL cholesterol decreased. In those with UA, the LDL number increased without elevation of LDL cholesterol, indicating typical hyperbetalipoproteinemia. The subjects with atherothrombotic brain infarction, an increased number of small-sized LDLs was noted. In those with ASO, the number of VLDL and IDL increased with small LDL. HDL cholesterol decreased in those with CAD, cerebrovascular disease, and ASO. Since similar quantitative and qualitative alterations of apoB-containing lipoprotein have been observed in NIDDM patients as well as in those with macrovascular diseases, diabetic patients are thought to be more susceptible to the initiation and progression of atheromatous lesions in coronary, brain, and peripheral arteries.

Adult↗
PubMed1996

Mechanism and clinical implication of insulin resistance syndrome.

The insulin resistance syndrome has been noted as an interesting and important new risk factor for coronary artery disease. The syndrome consists of hypertension, glucose intolerance, and dyslipidemia, all of which are likely to be derived from insulin insensitivity. In subjects with nonobese and nondiabetic essential hypertension, steady-state plasma glucose (SSPG) was higher than in normotensive subjects during an insulin sensitivity test, indicating reduced insulin sensitivity to glucose metabolism in the hypertensive group. SSPG correlated with the percentage decrease of branched chain amino acids, free fatty acids, and serum potassium during the insulin sensitivity test. With a 2-h insulin infusion, serum norepinephrine, epinephrine, plasminogen activator inhibitor 1, and intraplatelet Ca2+ decreased significantly, but 6-keto-prostaglandin (PG) F1 alpha and PGE2 did not change. Insulin resistance decreased by using antihypertensive treatments with bunazosin, cilazapril, amlodipine, and benidipine in hypertensive subjects. Diagnostic criteria for the insulin resistance syndrome, including clinical values for each risk factor, were developed. Lowered insulin sensitivity and hyperinsulinemia were demonstrated in subjects with both vasospastic and coronary artery stenotic angina. The insulin resistance syndrome together with hyperinsulinemia is likely to induce atherosclerotic changes, possibly through reduced rather than excessive action of insulin.

Angina Pectoris↗
PubMed1996

Demonstration of insulin resistance in coronary artery disease documented with angiography.

OBJECTIVE: To evaluate the relation between insulin resistance and coronary atherosclerosis, insulin sensitivity in lean nondiabetic, normotensive subjects with and without obstructive coronary artery disease (CAD). The correlation between insulin resistance and degree of coronary stenosis was also investigated. RESEARCH DESIGN AND METHODS: Four groups were studied: 1) nine subjects with normal glucose tolerance (NGT) without CAD, 2) 10 subjects with NGT with CAD, 3) nine subjects with impaired glucose tolerance (IGT) without CAD, and 4) 10 subjects with IGT with CAD. Insulin sensitivity was determined by the steady-state plasma glucose (SSPG) method using Sandostatin. Coronary angiography was performed in all study subjects, and the severity of coronary artery atherosclerosis was quantified in a modified Gensini score. RESULTS: The SSPG (millimoles per liter) levels were significantly higher in the patients with CAD compared with control subjects (control vs. patient group: 4.8 +/- 0.5 vs. 7.9 +/- 0.9 with NGT, P < 0.05; 5.6 +/- 0.5 vs. 11.1 +/- 0.8 with IGT, P < 0.001), indicating the presence of insulin resistance in patients with CAD. The coronary atherosclerosis score (CAS) was significantly and positively correlated with SSPG (r = 0.74, P < 0.05) and 2-h insulin area (r = 0.78, P < 0.01) in NGT subjects with CAD. On the other hand, the percentage fall of plasma free fatty acid (0-30 min) during an insulin sensitivity test was significantly decreased in the subjects with CAD and was inversely correlated with the CAS (r = -0.43, P < 0.05), especially in NGT subjects with CAD. CONCLUSIONS: These data suggest that in patients with CAD, insulin-mediated glucose metabolism is significantly impaired, and a significant correlation was noted between insulin resistance and severity of CAD. Therefore, the hyperinsulinemia often observed in patients with CAD is attributable to the compensatory mechanism of the beta-cell to the inadequate action of insulin for glucose metabolism. Hyperinsulinemia in the presence of insulin resistance aggravates dyslipidemia and may stimulate the atheromatous process by an as-yet-unknown mechanism.

Adult↗