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Biomedical subjects

M Minami

Publications and source records attributed to M Minami.

At least 289 records · Page 16Linked to original sources

[Application of heparin-coated percutaneous cardiopulmonary support system to elective cardiac and aortic operations].

Non emergency use of heparin-coated percutaneous cardiopulmonary support (PCPS) in cardiovascular surgery was applied in 4 patients (3 patients with descending aortic aneurysm, and one with aortic valvular stenosis and impaired left ventricular contractility (LVEF = 0.18). In aortic surgery, femoral inflow and outflow cannulae were inserted after introduction of anesthesia, and low flow F F bypass was established with the patient in supine position. Subsequently lateral posture was taken for aortic grafting. Activated clotting time was kept around 200 sec during the whole operative period and F F bypass was continued after the grafting procedure, and the cannulae were removed when the patient posture was returned to supine. With this method cannulation and decannulation were easy, and almost prone position, which was sometimes necessary for dissection of the adhesion of lung to the posterior aspect of the aneurysmal wall, was easily performed. Because of the percutaneous insertion, there was no local hemorrhage in the groin. Heparin coating circuit permitted only low grade systemic anticoagulation during the operative period, which could lead to decreased amount of hemorrhage. Long F F bypass without full heparinization made no harmful effect on patients' coagulability nor their hemodynamic status. For the patient with extremely impaired cardiac contractility, "scheduled PCPS and IABP" was proved to be safe, reliable, and cost-effective: F F bypass was established before sternotomy, and intracardiac procedure with aortic crossclamping was performed under total cardiopulmonary bypass using PCPS. After declamping of the aorta, weaning from the bypass was not tried and total anticoagulation was reversed with protamine. Then the sternum was closed and patient was transferred to ICU with the PCPS and IABP on. After more than 10 hours, when the cardiac contractility recovered from the intraoperative ischemic insult to a considerable degree, weaning from PCPS was successfully accomplished.

Adult↗

[Analysis of the profile of CD4+ cells in Behçet's disease].

The cell-mediated immune response and disorders of the cytokine-producing cells play an important role in the pathogenic mechanisms of Behçet's disease. Recently, CD4+ T helper cells have been categorized into at least two distinct subsets based on their profiles of cytokine production. We analyzed the number of interleukin (IL)-2 producing type 1 helper T (Th1) cells and IL-4 producing Th2 cells from 22 patients (male: 12, female: 10) with Behçet's disease and 19 normal controls (male: 9) by flow cytometric analysis. The patients with Behçet's disease were categorized into two groups by the activity of ocular inflammation; one group comprised the active cases (13 patients) and the other the inactive cases (9 patients). Peripheral blood mononuclear cells (PBMCs) from patients and normal controls were stimulated with immobilized anti-CD3 mAb for 6 hours and immunostained with anti IL-2 and anti IL-4 mAbs followed by fluorescein isothiocyanate (FITC) conjugated 2nd Abs. The number of IL-2 producing CD4+ cells in Behçet's disease patients with active uveoretinitis was significantly higher than that from both inactive cases (p < 0.005) and controls (p < 0.01). In contrast, the number of IL-4 producing CD4+ cells showed no significant difference among the groups. These results may indicate that Th1 cells play an important role in the immunopathogenesis of ocular inflammation of Behçet's disease. Thus, analysis of Th subsets in Behçet's disease may be useful for management of the disease.

Adult↗

Vitamin E ameliorates the renal injury of Dahl salt-sensitive rats.

Recently, hyperlipidemia as well as hypertension has been observed in Dahl salt-sensitive (S) rats. In this study, to investigate whether the lipid abnormality is involved in the renal injury of Dahl S rats, we examined the effect of vitamin E on glomerular sclerosis, as vitamin E is an inhibitor of lipid oxidation. Dahl S rats were given a high salt diet (8% NaCl) containing either normal vitamin E (2 mg/100 g) or high vitamin E (50 mg/100 g) for 4 weeks. Dahl salt-resistant (R) rats were given a high salt and normal vitamin E diet. The blood pressure in the Dahl rats increased and was not suppressed by the vitamin E supplement. Serum cholesterol and triglycerides in Dahl S rats were higher than in Dahl R rats at both 0 and 4 weeks. Vitamin E lowered the serum cholesterol level in Dahl S rats at 4 weeks (126 +/- 5 v 150 +/- 12 mg/dL, P < .01). Urinary protein excretion and serum creatinine increased in Dahl S rats, and vitamin E inhibited the increases significantly (urinary protein, 70.7 +/- 0.9 v 178.0 +/- 8.8 mg/day, P < .01; serum creatinine, 0.45 +/- 0.02 v 0.63 +/- 0.05 mg/dL, P < .01). Serum lipid peroxide (LPO) was higher in Dahl S rats than in Dahl R rats, and vitamin E lowered LPO in Dahl S rats (2.10 +/- 0.03 v 2.70 +/- 0.04 nmol/mL, P < .01). In the histologic study, sclerosing score (SS) of glomeruli, which represents the degree of glomerulosclerosis semiquantitatively, was higher in Dahl S rats than in Dahl R rats. Vitamin E lowered SS (114 +/- 3 v 157 +/- 6, P < .01) and ameliorated arterial injuries such as medial thickness with partial necrosis and severe fibrinoid proliferation with inflammatory cell infiltration. In all rats, SS was strongly correlated with urinary protein (r = 0.93, P < .01), serum cholesterol (r = 0.86, P < .01), and serum LPO (r = 0.89, P < .01). These results suggest that the renal injury in Dahl S rats is caused not only by hypertension but also by hyperlipidemia. Therefore, vitamin E might ameliorate the renal damage by inhibiting the oxidation of lipids.

Animals↗

[Opioid receptors].

Explore the source record for details and available documents.

Adenylyl Cyclases↗

[A clinical evaluation of the Hepcon/HMS: a new device of monitoring hemostasis management during cardiopulmonary bypass].

BACKGROUND: The "Hepcon/HMS", a small, protable console which can instantaneously measure residual whole blood heparin concentration and automatically compute the necessary dose of additional heparin during extracorporeal circulation and also compute the required dose of protamine to reverse the effect of residual heparin. METHOD: This study was performed in 32 consecutive patients undergoing primary elective cardiac operation between March and July 1996. Patients were divided randomly in two groups: control group and "Hepacon/HMS" group. Hematologic factors, total heparin dose, total protamine dose, postoperative bleeding and blood transfusion volume were compared between these two groups. RESULTS: Patients in the "Hepcon/HMS" group received significantly greater doses of heparin (p = 0.01) and lower doses of protamine (p = 0.01) compared with the control patients. CONCLUSION: By using "Hepcon/HMS", smaller amount of protamine to reverse residual heparin was achieved without no hemostatic derangement nor increase in the amount of postoperative bleeding, irrespective of the fact that the greater amount of heparin was administered during extracorporeal circulation as compared with the conventional anticoagulation protocol. It may help prevent the undesirable side effects of administering excessive amount of protamine, including depression of myocardial function, platelet dysfunction, anaphylactic reaction and catastrophic circulatory collapse.

Cardiopulmonary Bypass↗

Inhibition of 5-hydroxytryptamine type 2A receptor-induced currents by n-alcohols and anesthetics.

5-Hydroxytryptamine type 2A receptors (5-HT2A) are G protein-coupled receptors that increase intracellular Ca2+ concentrations via activation of phospholipase C-beta and elevation of myo-inositol-1,4,5-triphosphate levels. In the central nervous system, these receptors are involved in regulating sleep and alertness. We now report that ethanol inhibited (IC50 = 41 mM) 5-HT2A receptor-induced Ca2+-dependent Cl- currents in Xenopus laevis oocytes. Pharmacologically relevant concentrations of other n-alcohols (propanol to octanol) also inhibited 5-HT responses; however, longer-chain alcohols (decanol, undecanol and dodecanol) had little or no effect. The protein kinase C inhibitor GF109203X and the nonspecific protein kinase inhibitor staurosporine abolished the inhibitory effects of ethanol and octanol on 5-HT2A receptors. GF109203X enhanced 5-HT2A receptor function when administered alone. In addition, the volatile anesthetics halothane and 1-chloro-1,2,2-trifluorocyclobutane decreased 5-HT2A responses in a concentration-dependent manner. The inhibitory effects of the volatile anesthetics were also attenuated in oocytes treated with GF109203X. The intravenous anesthetics propofol, ketamine, pentobarbital and etomidate did not affect 5-HT2A receptor function. The modulation of 5-HT2A receptor-dependent current was also investigated using two novel halogenated compounds that do not produce anesthesia. The nonanesthetic compound 2,3-chloro-octafluorobutane had no effects on 5-HT-induced currents; however, the nonanesthetic compound 1,2-dichlorohexafluorocyclobutane had an inhibitory effect at lower concentrations than the predicted anesthetic concentration. Thus, 5-HT2A receptors are inhibited by alcohols and volatile anesthetics, and these actions are dependent on protein kinase C.

Anesthetics↗

[An analysis of type 2 helper T cells in patients with atopic dermatitis].

In order to know the role of type 2 helper T (Th2) cells on patients with atopic dermatitis (AD), peripheral blood mononuclear cells were taken from the patients, stimulated with immobilized anti CD3 monoclonal antibody in the presence of monensin, and stained with fluorescein isothiocyanate-labeled anti IL-2 or IL-4 monoclonal antibody, followed by phycoerythrin labeled-anti CD4 monoclonal antibody. The fluorescent intensity was detected by FACScan. The results showed that the frequency of IL-4 producing CD4+ cells from AD patients was significantly higher than that from the healthy controls, whereas that of IL-2 producing CD4+ cells from patients were the same as healthy controls. The frequency of IL-4 producing cells was well correlated to the clinical severity of the disease, but that of IL-2 producing cells did not show any significance. Neither IL-2 nor IL-4 producing CD4+ cells had any relation to the serum IgE levels and the number of eosinophils in the patients. Our results indicate dominance of IL-4 producing CD4+ cells, which means Th2 cells in the peripheral mononuclear cells in the patients with AD, especially severe cases.

Adult↗

Cyclophosphamide increases 5-hydroxytryptamine release from the isolated ileum of the rat.

We recently reported that chronic administration of cyclophosphamide significantly increased urinary 5-hydroxyindole acetic acid (5-HIAA) excretion in rats indicative of a release of 5-hydroxytryptamine (5-HT) from intestinal enterochromaffin (EC) cells. Cyclophosphamide is considered to be an inactive prodrug and require conversion to active emetic metabolities (e.g. phosphoramide mustard) by hepatic metabolism. However the presence of cytochrome P450 in the intestine raises the possibility of cyclophosphamide metabolism in the wall of the intestine, a site which would have considerable significance for 5-HT release and the emetic effects of cyclophosphamide. The aim of this study was to investigate whether cyclophosphamide could induce the release of 5-HT from the isolated ileum and to examine its mechanism of action. Cyclophosphamide (10(-6)M and 10(-7)M) induced a concentration dependent increase of 5-HT from rat isolated ileum. This cyclophosphamide-induced 5-HT release was significantly reduced by granisetron (10(-6)M and 10(-7)M) or atropine (10(-7)M and 10(-6)M). Tetrodotoxin (10(-6)M completely inhibited the increased 5-HT release induced by cyclophosphamide. These results suggest that cyclophosphamide has the capacity to induce 5-HT release via activation of enteric cholinergic neurons. In addition the in vitro study demonstrate for the first time that cyclophosphamide may be activated to emetic metabolites at extra-hepatic sites (e.g. intestine) and that conversion at these sites could contribute to the mechanism of cyclophosphamide induced emesis.

Animals↗

IFN-gamma induces expression of MHC class I molecules in adult mouse dorsal root ganglion neurones.

The expression of major histocompatibility complex (MHC) class I molecules on adult mouse DRG neurones was analysed using immunofluorescence and reverse transcription-polymerase chain reaction (RT-PCR). MHC class I molecules were not expressed in untreated dorsal root ganglion (DRG) neurones. The molecules, however, were detected on the surface of neurones following IFN-gamma treatment. In addition, expression of the MHC class I beta 2-microglobulin and genes was induced in neurones following IFN-gamma treatment. Expression of Tap-1 and Lmp-2 genes, which are involved in antigen processing and presentation, was also induced by IFN-gamma treatment. These results indicated that DRG neurones are able to express MHC class I molecules following IFN-gamma treatment and suggest that DRG neurones themselves are susceptible to recognition by cytotoxic T cells.

Animals↗

Ectopic expression of CHOP (GADD153) induces apoptosis in M1 myeloblastic leukemia cells.

CHOP (GADD153) is a member of the C/EBP family and a stress-induced protein. To investigate the role of CHOP in cellular growth, we expressed CHOP conditionally in M1 myeloblastic leukemia cells that do not express p53 protein. More than 60% of M1 cells died through apoptosis 72 h after CHOP induction. Site-directed mutagenesis revealed that this process requires leucine zipper domain but neither intact basic region nor trans-activation domain. CHOP-mediated apoptosis accompanied downregulation of bcl-2 mRNA and overexpression of Bcl-2 delayed the process. Our results indicate that CHOP can induce apoptosis in a p53-independent manner.

Animals↗

Pharmacological characterization of KT-90 using cloned mu-, delta- and kappa-opioid receptors.

We analyzed the pharmacological characteristics of (-)-3-acetyl-6 beta-acetylthio-N-cyclopropylmethyl-normorphine (KT-90) using Chinese hamster ovary (CHO) cells expressing cloned rat mu-, delta- and kappa-opioid receptors. KT-90 displaced the specific binding of the following radiolabeled ligands selective to the mu-, delta- and kappa-opioid receptors, [3H][D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO), [3H][D-Pen2,D-Pen5]enkephalin (DPDPE), [3H] (+)-(5 alpha, 7 alpha, 8 beta)-N-methyl-N-[7-(1-pyrrolidinyl) l-oxaspiro-(4,5)dec-8-yl]benzeneacetamide (U69,593), with Ki values of 3.3 +/- 0.7, 22.8 +/- 1.5 and 1.9 +/- 0.3 nM, respectively In CHO cells expressing the mu-, delta- and kappa-opioid receptors, KT-90 inhibited forskolin (10 microM)-induced cyclic AMP accumulation in a concentration-dependent manner with IC50 values of 2337 +/- 750, 17.3 +/- 4.6 and 2.0 +/- 0.1 nM, respectively. The maximal inhibitory effects of KT-90 in the cells expressing mu-, delta- and kappa-opioid receptors were significantly lower than those of the type-selective agonists DAMGO, DPDPE and U69,593, respectively. These results indicated that KT-90 acts as a partial agonist on mu-, delta- and kappa-opioid receptors. KT-90 (10 and 100 nM), when added with morphine, produced a rightward shift of the concentration-response curve of morphine to inhibit the cyclic AMP accumulation in CHO cells expressing mu-, but not delta- or kappa-, opioid receptors. This finding is consistent with the findings that lower doses of KT-90 antagonize morphine analgesia in vivo.

Animals↗

Co-localization of mu opioid receptor is greater with dynorphin than enkephalin in rat striatum.

Using a combination of radioactive and non-radioactive in situ hybridization, the mu opioid receptor mRNA was localized in enkephalin as well as dynorphin neurones of the rat striatum. The proportion of enkephalin neurones showing co-localized mu opioid receptor mRNA was dependent on the rostrocaudal level (17-39% in rostral/intermediate levels vs 0.4-5% caudally) but did not differ between striatal subregions. For dynorphin neurones the reverse was true, with consistently higher levels of co-localization in the caudate-putamen (56-77%) than the nucleus accumbens (15-43%), but no differences along the rostrocaudal axis. Furthermore, the degree of enkephalin/mu co-localization was significantly lower than that of dynorphin/mu. These results suggest a fine-grained topological differentiation of mu receptor modulation of striatal opioid systems.

Animals↗

Interleukin (IL)-1 beta, IL-2, IL-4, IL-6 and transforming growth factor-alpha levels are elevated in ventricular cerebrospinal fluid in juvenile parkinsonism and Parkinson's disease.

Interleukin (IL)-1 beta , IL-2, IL-4, IL-6, epidermal growth factor (EGF), and transforming growth factor (TGF)-alpha were measured for the first time in ventricular cerebrospinal fluid (VCSF) from control non-parkinsonian patients, patients with juvenile parkinsonism (JP) and patients with Parkinson's disease (PD) by highly sensitive sandwich enzyme immunoassays. All cytokines were detectable in VCSF from control and parkinsonian patients, and the concentrations were much higher than those in lumbar CFS. The concentrations of IL-1 beta, IL-2, IL-4 and TGF-alpha in VCSF were higher in JP than those in controls (P < 0.05). In contrast, the concentrations of IL-2 and IL-6 in VCSF from patients with PD were higher than those from control patients (P < 0.05). These results agree with our previous reports, in which the cytokine levels were elevated in the striatal dopaminergic region of the brain from patients with PD. Since VCSF is produced in the ventricles, the alteration of cytokines in VCSF may reflect the changes of cytokines in the brain. Because cytokines play an important role as mitogens and neurotrophic factors in the brain, the increases in cytokines as a compensatory response may occur in the brain of patients of JP or PD during the progress of neurodegeneration. Increase in cytokines may contribute not only as a compensatory response but as a primary initiating trigger for the neurodegeneration.

Adolescent↗

STAT3 activation is a critical step in gp130-mediated terminal differentiation and growth arrest of a myeloid cell line.

Myeloid leukemia M1 cells can be induced for growth arrest and terminal differentiation into macrophages in response to interleukin 6 (IL-6) or leukemia inhibitory factor (LIF). Recently, a large number of cytokines and growth factors have been shown to activate the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) signaling pathway. In the case of IL-6 and LIF, which share a signal transducing receptor gp130, STAT3 is specifically tyrosine-phosphorylated and activated by stimulation with each cytokine in various cell types. To know the role of JAK-STAT pathway in M1 differentiation, we have constructed dominant negative forms of STAT3 and established M1 cell lines that constitutively express them. These M1 cells that overexpressed dominant negative forms showed no induction of differentiation-associated markers including Fc gamma receptors, ferritin light chain, and lysozyme after treatment with IL-6. Expression of either c-myb or c-myc was not downregulated. Furthermore, IL-6- and LIF-mediated growth arrest and apoptosis were completely blocked. Thus these findings demonstrate that STAT3 activation is the critical step in a cascade of events that leads to terminal differentiation of M1 cells.

Acute-Phase Proteins↗

Essential role of Stat6 in IL-4 signalling.

Interleukin-4 (IL-4) is a pleiotropic lymphokine which plays an important role in the immune system. IL-4 activates two distinct signalling pathways through tyrosine phosphorylation of Stat6, a signal transducer and activator of transcription, and of a 170K protein called 4PS. To investigate the functional role of Stat6 in IL-4 signalling, we generated mice deficient in Stat6 by gene targeting. We report here that in the mutant mice, expression of CD23 and major histocompatibility complex (MHC) class II in resting B cells was not enhanced in response to IL-4. IL-4 induced B-cell proliferation costimulated by anti-IgM antibody was abolished. The T-cell proliferative response was also notably reduced. Furthermore, production of Th2 cytokines from T cells as well as IgE and IgG1 responses after nematode infection were profoundly reduced. These findings agreed with those obtained in IL-4 deficient mice or using antibodies to IL-4 and the IL-4 receptor. We conclude that Stat6 plays a central role in exerting IL-4 mediated biological responses.

Animals↗

Biphasic effects of intracerebroventricular interleukin-1 beta on mechanical nociception in the rat.

The effects of interleukin-1 beta on the mechanical nociceptive threshold in rat were examined using the paw-pressure test. An intracerebroventricular (i.c.v.) injection of interleukin-1 beta at doses of 10 and 100 pg/rat caused hyperalgesia to mechanical stimuli. Higher doses of interleukin-1 beta (1 and 10 ng/rat) induced an analgesic effect. The coadministration of the interleukin-1 receptor antagonist completely antagonized the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v. injection of alpha-helical-corticotropin-releasing factor [9-41] 15 min prior to interleukin-1 beta administration completely blocked the hyperalgesic and analgesic effects of interleukin-1 beta. An i.c.v. injection of sodium salicylate 15 min prior to interleukin-1 beta administration inhibited the hyperalgesic effect of interleukin-1 beta, but not the analgesic effect. These results suggest that interleukin-1 beta produces biphasic effects on the mechanical nociceptive threshold through the interleukin-1 receptor in the brain and that a corticotropin-releasing factor-mediated pathway is involved. Furthermore, the hyperalgesic effect of interleukin-1 beta may be mediated by prostaglandins.

Animals↗

Induction of interleukin-1 beta mRNA in the hypothalamus following subcutaneous injections of formalin into the rat hind paws.

The induction of interleukin-1 beta (IL-1 beta) mRNA in the rat brain following subcutaneous injection of formalin into the hind paws was investigated by in situ hydridization. IL-1 beta mRNA was markedly induced in the hypothalamus after the injection of formalin into both hind paws. On the other hand, IL-1 beta mRNA was scarcely observed in the hypothalamus of saline-injected control rats. The type of cells expressing IL-1 beta mRNA was likely glia because their nuclei were densely stained by Cresyl violet and were relatively small. The present results suggest that IL-1 beta mRNA is induced in the glial cells of the hypothalamus by persistent pain which is caused by formalin injection.

Animals↗