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Biomedical subjects

H Ishihara

Publications and source records attributed to H Ishihara.

At least 145 records · Page 8Linked to original sources
PubMed1999

Relaxant effect of propofol on the airway in dogs.

Propofol has been suggested to produce airway relaxant effects in vivo, although the mechanism is unclear. We have evaluated the bronchodilating effect of propofol using a direct visualization method with a superfine fibreoptic bronchoscope. We studied 21 mongrel dogs anaesthetized with pentobarbital 30 mg kg-1 i.v. and pancuronium 0.2 mg kg-1 h-1. The animals were allocated randomly to one of three groups (n = 7 in each): propofol group, atropine-propofol group and histamine-propofol group. The trachea was intubated using a tracheal tube that had a second lumen for insertion of the bronchoscope to monitor continuously bronchial cross-sectional area (BCA). BCA was measured using the NIH Image program. In the propofol group, dogs were given the following doses of propofol at 10-min intervals: 0 (saline), 0.2, 2.0 and 20 mg kg-1 i.v. In the atropine-propofol group, saline, atropine 0.2 mg kg-1 and propofol 20 mg kg-1 were given at 10-min intervals. In the histamine-propofol group, bronchoconstriction was elicited with histamine 10 micrograms kg-1 and 500 micrograms kg-1 h-1 until the end of the experiment. Thirty minutes after the start of infusion of histamine, propofol (0, 0.2, 2.0 and 20 mg kg-1) was administered. Changes in BCA were expressed as percentage of basal area. Histamine decreased BCA by 39.2 (SEM 5.4%). Propofol increased significantly basal and histamine-decreased BCA in a dose-dependent manner by 18.4 (4.5%) and 15.8 (4.9%), respectively after 20 mg kg-1 i.v. However, propofol following atropine i.v. did not increase BCA (129.9 (8.2)% after atropine vs 125.7 (8.9)% after propofol). Therefore, the relaxant effect of propofol may be a result of reduction in vagal tone.

Anesthetics, Intravenous↗
PubMed1999

Relaxant effect of magnesium and zinc on histamine-induced bronchoconstriction in dogs.

OBJECTIVE: Magnesium sulfate (MgSO4) has been reported to produce bronchodilation in asthmatic patients. In vitro studies have suggested that divalent cations inhibit L-type voltage-sensitive calcium ion (Ca2+) channels in cardiac and smooth muscles. In this study, we evaluated the in vitro and in vivo effects of magnesium ion (Mg2+) and zinc ion (Zn2+) on the airway contracted by histamine. SETTING: A university research laboratory. SUBJECTS IN VITRO: Tracheal smooth muscle from guinea pigs. IN VIVO: Mongrel dogs. MEASUREMENTS AND MAIN RESULTS IN VITRO STUDY: The tension of isolated guinea pig tracheal strips was measured isometrically with a force displacement transducer. The specimen was contracted with histamine (10 microM). Then, MgSO4 (n = 6), zinc sulfate (ZnSO4, n = 6), or sodium sulfate (Na2SO4, n = 6) was cumulatively added to the organ bath. IN VIVO STUDY: The bronchial cross-sectional area of mongrel dogs was measured by a direct visualization method demonstrated previously. The dogs were randomly assigned to three groups: group Mg (n = 7), group Zn (n = 7), and group Na (n = 7). Bronchoconstriction was elicited with histamine (10 microg/kg plus 500 microg/kg/hr iv). Thirty minutes after the start of histamine infusion, 0 (saline), 1, 10, and 100 micromol/kg ZnSO4 or 1, 10, 100, and 1000 micromol/kg MgSO4 or Na2SO4 were administered intravenously in group Zn, Mg, or Na, respectively. The bronchial cross-sectional area was assessed before (basal) and 30 mins after the start of histamine infusion and 5 mins after each dose of ZnSO4, MgSO4, or Na2SO4. Arterial blood was also obtained to measure plasma levels of epinephrine and norepinephrine by gas chromatography-mass spectrometry. All data are expressed as mean +/- SEM. The doses of the divalent cations that reversed histamine-induced contraction by 50% were calculated by GraphPad Prism. MgSO4 and ZnSO4 (9.38+/-0.28 and 1.84+/-0.30 mM, respectively) relaxed histamine-contracted tracheal strip in a concentration-dependent manner, whereas Na2SO4 did not. Similarly, the in vivo study showed that MgSO4 and ZnSO4 dose-dependently reversed histamine-induced bronchoconstriction (potency, ZnSO4 > MgSO4), whereas Na2SO4 did not. In groups Mg and Zn, the plasma catecholamine levels also dose-dependently increased except when 1000 micromol/kg MgSO4 was administered. CONCLUSION: Because the divalent cations tested produced a spasmolytic effect on the contracted airway, infusion of divalent cations might be effective against asthmatic attack. However, high concentrations of these cations produce significant toxicity, so dosage will be an important concern in development of these agents.

Animals↗
PubMed1999

Prostaglandin E1 produces spasmolytic effects on histamine-induced bronchoconstriction in dogs.

OBJECTIVE: In this study, we evaluated the spasmolytic effect of intravenous prostaglandin (PG) E1 on histamine-induced bronchoconstriction with a direct visualization method using a superfine fiberoptic bronchoscope. SETTING: A university research laboratory. SUBJECTS: Mongrel dogs. INTERVENTIONS: The bronchial cross-sectional area (BCA) of mongrel dogs was measured by a direct visualization method using a superfine fiberoptic bronchoscope. Bronchoconstriction was elicited with histamine (H) infusion: 10 microg/kg iv bolus + 500 microg/kg/h continuous iv. The first protocol (n = 7) was designed to determine the effects of intravenous bolus of PGE1: 0 (saline), 0.01, 0.1, 1.0 and 10 microg/kg on H-induced bronchoconstriction. BCA was assessed before and 30 min after starting the H infusion and 5 min after each dose of intravenous PGE1. The second protocol was designed to determine whether continuous intravenous infusion of PGE1 reverses H-induced bronchoconstriction. In the PG group (n = 6), PGE1 was continuously infused at 0.1 microg/kg/min (20 mL/hr). In the control group (n = 6), saline was administered at a rate of 20 mL/hr iv. BCA was assessed before and 30 min after starting the H-infusion and at 5, 10, 30 and 60 min after commencing the PGE1 or saline infusion. Arterial blood was obtained simultaneously for measurement of plasma concentrations of epinephrine and norepinephrine by gas chromatography mass spectrometry. MEASUREMENTS AND MAIN RESULTS: In the first protocol, PGE1 produced a dose-dependent increase in the percentage of BCA and 10 microg/kg of PGE1 almost fully reversed the H-induced bronchoconstriction. Plasma catecholamines did not change significantly. In the second protocol, continuous infusion of PGE1 produced a time-dependent reversal of H-induced bronchoconstriction (percentage of BCA increased to 80.0+/-9.0% 60 min after the start of PGE1 infusion), whereas saline infusion did not reverse the bronchoconstriction. Plasma catecholamines did not change significantly in either group. CONCLUSIONS: Both intravenous bolus and continuous intravenous infusion of PGE1 reversed the H-induced bronchoconstriction. PGE1 may be used safely for patients with the hyperreactive airway and might be useful as a therapeutic agent for these patients.

Alprostadil↗
PubMed1999

Coadministration of basic fibroblast growth factor and sucrose octasulfate (sucralfate) facilitates the rat dorsal flap survival and viability.

The effective use of local growth factors and cytokines may replace the lengthy staged surgical delay process. We tested the efficacy of basic fibroblast growth factor (bFGF) coadministered with sucralfate (sucrose octasulfate) on the rat dorsal flap model. A total of 76 male Wistar rats were used in this experiment. Four groups of the animals were divided. Group 1 (n = 5) was the vehicle control (saline soaked), group 2 (n = 5) was sucrose octasulfate soaked (100 microg/ml, 1 ml), group 3 (n = 5) was bFGF soaked (1 microg/ml, 1 ml), and group 4 (n = 5) was both bFGF and sucrose octasulfate soaked. All agents were soaked equally in Gelfoam. The flap survival measured by the quantitative computer-assisted morphologic analysis was significantly improved by day 5 postoperatively in the combined administration group compared with the vehicle control (81 and 53 percent, respectively; p < 0.05). In lead oxide-gelatin microangiography, there was enhanced pedicle vessel formation observed as well as the extended vessel sprouting up to very close to the distal end in combined group on day 5. The endogenous bFGF mRNA expressions shown by reverse transcriptase-polymerase chain reaction were detected in all four groups. The angiogenesis indicated by alpha-smooth muscle actin immunopositivity was significantly more enhanced in the combined group than the vehicle control (37.3 and 19.4, respectively; p < 0.01). In the combined group, there was stronger immunopositivity for bFGF in epidermis and hair follicles observed, and more notably bFGF-immunopositive dermal fibroblasts were evident. Thus, coadministration of bFGF and sucralfate markedly facilitates the rat dorsal flap survivability by enhancing the bFGF expression and angiogenesis.

Actins↗
PubMed1999

Pituitary-adrenal and parasympathetic function in chronic schizophrenic patients with postoperative ileus or hypotension.

We studied the relationship between parasympathetic, sympathetic and pituitary-adrenal functions in chronic schizophrenic patients with complications such as postoperative paralytic ileus and hypotension during anaesthesia. Plasma epinephrine, norepinephrine (NE), adrenocorticotropin (ACTH), cortisol and the coefficient of variation (CV) of the R-R intervals on the electrocardiogram (ECG) as parasympathetic parameter were measured in schizophrenic and control patients. The CV value of the R-R interval on the ECG before the start of anaesthesia was significantly decreased to 2.3 +/- 0.2 in the schizophrenic patients as compared with 3.5 +/- 0.3 of the control patients. The CV value of the R-R interval on the ECG in schizophrenic patients with postoperative paralytic ileus was more diminished to 1.6 +/- 0.2. The CV values in schizophrenic patients with and without hypotension during anaesthesia were similar and we could not find any significant difference. Chronic schizophrenic patients developed a decrease in NE, ACTH and cortisol responses to surgical stress, while there were no significant differences in these hormonal changes between those patients with and without paralytic ileus and hypotension during anaesthesia. In conclusion, the CV value of the ECG R-R interval may be correlated inversely with the expectancy of postoperative ileus in chronic schizophrenic patients. Their suppressed pituitary-adrenal function and sympathetic system may be indirectly associated with the paralytic ileus and hypotension.

Adrenocorticotropic Hormone↗
PubMed1999

Protease-activated receptors 1 and 4 mediate activation of human platelets by thrombin.

Because of the role of thrombin and platelets in myocardial infarction and other pathological processes, identifying and blocking the receptors by which thrombin activates platelets has been an important goal. Three protease-activated receptors (PARs) for thrombin -- PAR1, PAR3, and PAR4 -- are now known. PAR1 functions in human platelets, and the recent observation that a PAR4-activating peptide activates human platelets suggests that PAR4 also acts in these cells. Whether PAR1 and PAR4 account for activation of human platelets by thrombin, or whether PAR3 or still other receptors contribute, is unknown. We have examined the roles of PAR1, PAR3, and PAR4 in platelets. PAR1 and PAR4 mRNA and protein were detected in human platelets. Activation of either receptor was sufficient to trigger platelet secretion and aggregation. Inhibition of PAR1 alone by antagonist, blocking antibody, or desensitization blocked platelet activation by 1 nM thrombin but only modestly attenuated platelet activation by 30 nM thrombin. Inhibition of PAR4 alone using a blocking antibody had little effect at either thrombin concentration. Strikingly, simultaneous inhibition of both PAR1 and PAR4 virtually ablated platelet secretion and aggregation, even at 30 nM thrombin. These observations suggest that PAR1 and PAR4 account for most, if not all, thrombin signaling in platelets and that antagonists that block these receptors might be useful antithrombotic agents.

Adenosine Triphosphate↗
PubMed1999

Overexpression of monocarboxylate transporter and lactate dehydrogenase alters insulin secretory responses to pyruvate and lactate in beta cells.

Previous investigations revealed low activities of lactate dehydrogenase (LDH) and plasma membrane monocarboxylate transporters (MCT) in the pancreatic beta cell. In this study the significance of these characteristics was explored by overexpressing type A LDH (LDH-A) and/or type 1 MCT (MCT-1) in the clonal INS-1 beta cells and isolated rat islets. Inducible overexpression of LDH-A resulted in an 87-fold increase in LDH activity in INS-1 cells. Adenovirus-mediated overexpression of MCT-1 increased lactate transport activity 3.7-fold in INS-1 cells. Although overexpression of LDH-A, and/or MCT-1 did not affect glucose-stimulated insulin secretion, LDH-A overexpression resulted in stimulation of insulin secretion even at a low lactate concentration with a concomitant increase in its oxidation in INS-1 cells regardless of MCT-1 co-overexpression. Adenovirus-mediated overexpression of MCT-1 caused an increase in pyruvate oxidation and conferred pyruvate-stimulated insulin release to isolated rat islets. Although lactate did not stimulate insulin secretion from control or MCT-1-overexpressing islets, co-overexpression of LDH-A and MCT-1 evoked lactate-stimulated insulin secretion with a concomitant increase in lactate oxidation in rat islets. These results suggest that low expression of MCT and LDH is requisite to the specificity of glucose in insulin secretion, protecting the organism from undesired hypoglycemic actions of pyruvate and lactate during exercise and other catabolic states.

Adenoviridae↗
PubMed1999

Role of the Src homology 2 (SH2) domain and C-terminus tyrosine phosphorylation sites of SH2-containing inositol phosphatase (SHIP) in the regulation of insulin-induced mitogenesis.

To examine the role of SHIP in insulin-induced mitogenic signaling, we used a truncated SHIP lacking the SH2 domain (deltaSH2-SHIP) and a Y917/1020F-SHIP (2F-SHIP) in which two tyrosines contributing to Shc binding were mutated to phenylalanine. Wild-type (WT)-, deltaSH2-, and 2F-SHIP were transiently transfected into Rat1 fibroblasts overexpressing insulin receptors (HIRc). Insulin-stimulated tyrosine phosphorylation of WT-SHIP and deltaSH2-SHIP, whereas tyrosine phosphorylation of 2F-SHIP was not detectable, indicating that 917/1020-Tyr are key phosphorylation sites on SHIP. Although SHIP can bind via its 917/1020-Tyr residues and SH2 domain to Shc PTB domain and 317-Tyr residue, respectively, insulin-induced SHIP association with Shc was more greatly decreased in 2F-SHIP cells than that in deltaSH2-SHIP cells. Insulin stimulation of Shc association with Grb2, which is important for p21ras-MAP kinase activation, was decreased by overexpression of WT- and 2F-SHIP. Importantly, insulin-induced Shc x Grb2 association was not detectably reduced in deltaSH2-SHIP cells. In accordance with the extent of Shc association with Grb2, insulin-induced MAP kinase activation was relatively decreased in both WT-SHIP and 2F-SHIP cells, but not in deltaSH2-SHIP cells. To examine the functional role of SHIP in insulin's biological action, insulin-induced mitogenesis was compared among these transfected cells. Insulin stimulation of thymidine incorporation and bromodeoxyuridine incorporation was decreased in WT-SHIP cells compared with that of control HIRc cells. Expression of 2F-SHIP also significantly reduced insulin-induced mitogenesis, whereas it was only slightly affected by overexpression of deltaSH2-SHIP. Furthermore, the reduction of insulin-induced mitogenesis in WT-SHIP cells was partly compensated by coexpression of Shc. These results indicate that SHIP plays a negative regulatory role in insulin-induced mitogenesis and that the SH2 domain of SHIP is important for its negative regulatory function.

Adaptor Proteins, Signal Transducing↗
PubMed1999

Synergistic role of the phosphatidylinositol 3-kinase and mitogen-activated protein kinase cascade in the regulation of insulin receptor trafficking.

To examine the molecular mechanism of insulin receptor trafficking, we investigated the intracellular signaling molecules that regulate this process in Rat1 fibroblasts overexpressing insulin receptors. Cellular localization of insulin receptors was assessed by confocal laser microscopy with indirect immunofluorescence staining. Insulin receptors were visualized diffusely in the basal state. Insulin treatment induced the change of insulin receptor localization to perinuclear compartment. This insulin-induced insulin receptor trafficking was not affected by treatment of the cells with PI3-kinase inhibitor (wortmannin), whereas treatment with MEK [mitogen-activated protein (MAP) kinase-Erk kinase] inhibitor (PD98059) partly inhibited the process in a dose-dependent manner. Interestingly, treatment with both wortmannin and PD98059 almost completely inhibited insulin receptor trafficking. The functional importance of PI3-kinase and MAP kinase in the trafficking process was directly assessed by using single cell microinjection analysis. Microinjection of p85-SH2 and/or catalytically inactive MAP kinase ([K71A]Erk1) GST fusion protein gave the same results as treatment with wortmannin and PD98059. Furthermore, to determine the crucial step for the requirement of PI3-kinase and MAP kinase pathways, the effect of wortmannin and PD98059 on insulin receptor endocytosis was studied. Insulin internalization from the plasma membrane and subsequent insulin degradation were not affected by treatment with wortmannin and PD98059. In contrast, insulin receptor down-regulation from the cell surface and insulin receptor degradation, after prolonged incubation with insulin, were markedly impaired by the treatment. These results suggest that PI3-kinase and MAP kinase pathways synergistically regulate insulin receptor trafficking at a step subsequent to the receptor internalization.

Androstadienes↗
PubMed1999

Subcutaneous phaeohyphomycosis caused by Phaeoacremonium rubrigenum in an immunosuppressed patient.

BACKGROUND: Phaeohyphomycosis refers to infection by dematiaceous fungi with pigmented hyphae or yeast-like cells in the tissue. In humans, this disease is usually considered to be an opportunistic infection. The causal agents of phaeohyphomycosis include numerous species belonging to different genera and they are increasing as a result of the development of intensive medical therapy. OBSERVATION: We report the case of a 61-year-old Japanese female under corticosteroid treatment for malignant rheumatoid arthritis. An asymptomatic subcutaneous tumor developed on the back of her left foot. Histological examination of the excised material revealed mixed cell granuloma (H&E) and the presence of branched hyphal elements (periodic acid-Schiff). A fungus grown in pure culture was identified as Phaeoacremonium rubrigenum. CONCLUSION: The hyphomycete genus, Phaeoacremonium, was proposed in 1996 by Crous et al. Three species belonging to this genus have been isolated from clinical specimens: P. inflatipes, from a human toenail, human synovial fluid and human mycetoma of the foot, P. parasiticum, from a subcutaneous lesion on a kidney transplant patient and several other sources, and P. rubrigenum, from a human patient with pneumonia. To our knowledge, however, this is the first report of phaeohyphomycosis caused by Phaeoacremonium rubrigenum.

Female↗
PubMed1999

Axial symptoms after en bloc cervical laminoplasty.

Eighty-two patients were evaluated after cervical laminoplasty to explore measures that could minimize future postoperative axial complaints. Patients were divided into two groups: Group A--severe postoperative axial symptoms, and Group B--mild axial complaints. Japanese Orthopaedic Association outcomes scores were similar for the two groups. Radiologic studies demonstrated greater restriction of range of motion in Group A patients who had undergone longer and more extensive surgical procedures.

Adult↗
PubMed1998

Relative involvement of Shc tyrosine 239/240 and tyrosine 317 on insulin induced mitogenic signaling in rat1 fibroblasts expressing insulin receptors.

Shc is phosphorylated on Tyr-239/240 and/or Tyr-317, which serves as a docking site for Grb2. To clarify the relative involvement of Shc Tyr-239/240 and Tyr-317 in insulin-induced mitogenesis, we generated expression vectors for Y317F (1F)-Shc, Y239/240F (2F)-Shc, and Y239/240/317F (3F)-Shc, and stably transfected them into Rat1 fibroblasts expressing insulin receptors (HIRc). Insulin-induced Shc phosphorylation and subsequent association with Grb2 was enhanced in wild-type (WT)-Shc cell. In contrast, insulin-stimulated Shc phosphorylation and Shc.Grb2 association were significantly decreased in 1F-Shc and 3F-Shc cells, while these were only slightly affected and almost comparable in 2F cells compared with those in parental HIRc cells. The kinetics of MAP kinase activation closely paralleled the kinetics of Shc phosphorylation and Shc.Grb2 association. Thus, insulin stimulation of MAP kinase activation occurred more rapidly in WT-Shc cells, and the activation was delayed in 1F-Shc and 3F-Shc cells, while it was comparable in 2F-Shc cells compared with that in HIRc cells. Furthermore, WT-Shc cells displayed enhanced sensitivity to insulin stimulation of thymidine incorporation. Importantly, the sensitivity was significantly decreased in 1F-Shc and 3F-Shc cells, while it was almost comparable in 2F-Shc cells compared with that in HIRc cells. These results indicate that Shc Tyr-317 is more predominant insulin-induced phosphorylation site than Tyr-239/240 for coupling with Grb2 leading to MAP kinase activation and mitogenesis in Rat1 fibroblasts.

Adaptor Proteins, Signal Transducing↗
PubMed1998

Evidence for mRNA expression of vascular endothelial growth factor by X-ray irradiation in a lung squamous carcinoma cell line.

Vascular endothelial growth factor (VEGF) is a multipotent cytokine which plays an important role in various angiogenic conditions as well as in some tumor behaviors. Here we examined the induction of VEGF mRNA by X-ray irradiation in a lung squamous cell carcinoma cell line (RERF-LC-AI). Irradiating the cells with 15 Gy X-rays significantly increased the mRNA expression up to 2.5-fold of control at a post-irradiation time of 16-24 h. The induction of VEGF mRNA by X-ray irradiation was completely blocked by treating cells with either genistein (Src tyrosine kinase inhibitor) or H7 (protein kinase C inhibitor). This suggests that the mechanism of induction might be concerned with the pathway which triggers Src tyrosine kinase of the cell surface and the protein kinase C pathway.

Antineoplastic Agents↗
PubMed1998

4-Benzylamino-1-chloro-6-substituted phthalazines: synthesis and inhibitory activity toward phosphodiesterase 5.

We synthesized various 4-benzylamino-1-chloro-6-substituted phthalazines (15) and 4-benzylamino-1-chloro-7-substituted phthalazines (16) and evaluated their inhibitory activity toward phosphodiesterase 5 (PDE5) purified from porcine platelets. The PDE5-inhibitory activities of 15 were greater than those of the isomers (16). The preferred substituent at the 4-position of phthalazine was a (3-chloro-4-methoxybenzyl)amino group, and those at the 6-position were cyano, nitro, and trifluoromethyl groups. Compounds 15a (IC50 = 4.8 nM), 15f (3.5 nM), and 15i (5.3 nM) were more potent inhibitors than E4021 (8.6 nM). Compounds 15a and 15f also showed vasorelaxant activity in isolated porcine coronary arteries precontracted with prostaglandin F2alpha (10(-5) M). The EC50 values for vasorelaxant action of 15a, 15f, and E4021 were 150, 160, and 980 nM, respectively. These results show that novel PDE5 inhibitors possessing a potent vasorelaxant effect may exist among phthalazine derivatives.

3',5'-Cyclic-GMP Phosphodiesterases↗
PubMed1998

The clinical significance of u-FCC, an antigen of anti-fucosylceramide antibody found in urine, in patients with gastric and colorectal carcinoma.

BACKGROUND: It has already been shown that the production of fucosylceramide, an aberrant glycolipid, is associated with neoplastic changes in human tissues. The authors of this study designed a sandwich radioimmunoassay (RIA) using a mouse monoclonal anti-fucosylceramide antibody, PC47H, designated as PC/PC RIA, and measured the level of u-FCC, an antigen of PC47H, in the urine of cancer patients. METHODS: The cohort comprised 41 patients with gastric carcinoma, 35 with colorectal carcinoma, 34 with other malignancies, 14 with cholelithiasis, 18 with gastric ulcer, and 110 healthy individuals. The u-FCC was quantified by PC/PC RIA. The cutoff value of u-FCC was obtained from the 110 healthy individuals, and the rates of positivity for gastric and colorectal carcinoma patients were evaluated. RESULTS: The rates of u-FCC positivity were 63% for patients with gastric carcinoma and 69% for colorectal carcinoma patients. The rate was only 1% (1/110) for the healthy individuals. The u-FCC value did not correlate with the values of either CA 19-9 or carcinoembryonic antigen (CEA). In a combination assay of u-FCC with CA 19-9 and CEA, the positivity rates were 84% for gastric carcinoma patients and 85% for colorectal carcinoma patients. CONCLUSIONS: Gastric and colorectal carcinoma patients have significantly high levels of u-FCC in their urine compared with normal individuals.

Animals↗