Biomedical subjects
Publications and source records attributed to M Kurata.
1. Postprandial variation in blood viscosity was studied in beagle dogs. 2. Blood viscosity increased following feeding. This change was caused by haematocrit elevation, which resulted mainly from splenic contraction. 3. Haemoconcentration, plasma viscosity and erythrocyte deformability did not contribute to the postprandial increment in blood viscosity.
1. Erythrocyte antioxidant systems--superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and glutathione reductase (GR)--were discussed in relation to life-spans in some mammalian species. 2. The erythrocyte life-span of different mammals was found to be correlated with the levels of SOD, GSH-Px and GSH. 3. Data reviewed indicates that the erythrocyte life-span of each species is governed by both the oxygen radical formation and the efficiency of intrinsic antioxidant systems.
1. The levels of erythrocyte glutathione and the activities of its metabolizing enzymes--glutathione peroxidase (GSH-Px), glutathione S-transferase (GST) and glutathione reductase (GR)--were measured in four species of primates: human, rhesus monkey, common marmoset and common tree shrew. 2. There were marked differences in GSH-Px and GST activities among the primates, while GR activity and glutathione level were much less variable.
1. Effects of ATP level on GSH regeneration were studied in the rabbit and guinea-pig erythrocytes. 2. There was a species difference in the efficacy of adenine, inosine and glucose as substrates for ATP recovery in the erythrocytes. 3. Erythrocytes GSH regeneration rate was found to be dependent on the cellular level of ATP in both the species.
1. Phenol compounds (ellagic acid, quercetin and purpurogallin), glutathione analogues (S-hexylglutathione and S-octylglutathione) and a diuretic drug (ethacrynic acid) were compared for their inhibitory effects on glutathione S-transferase (GST), glutathione reductase (GR) and glutathione peroxidase (GSH-Px) in the canine erythrocytes. 2. All these compounds inhibited GST activity; quercetin was found to be the most potent inhibitor. 3. Ellagic acid, purpurogallin, quercetin and ethacrynic acid inhibited GR activity; S-hexylglutathione and S-octylglutathione had no effect on GR and GSH-Px activities. 4. Quercetin and purpurogallin inhibited GST non-competitively toward glutathione, whereas ellagic acid showed a competitive inhibition. Ellagic acid and purpurogallin inhibited GR non-competitively toward oxidized glutathione.
Fresh lamprey (F-La) or sardine (F-Sa) oil is known to contain a large amount of n-3 polyunsaturated fatty acids such as eicosapentaenoic (EPA) and docosahexaenoic (DHA) acids. When F-La or F-Sa was deodorized with steam at 280 degrees C under 1 mmHg for 1 h (H-La and H-Sa, respectively), the contents of EPA and DHA were reduced and unidentified peaks were newly detected by gas-liquid chromatography. To know the biological influences of these high-temperature deodorized oils, the sterilizing function of the macrophage against Listeria monocytogenes was investigated in male ddY mice fed H-La or H-Sa. One week feeding of H-La or H-Sa lowered the LD50 values of the bacteria injected intravenously. Numbers of the viable bacteria on the day 3 after intravenous injection were about 10 times higher in the liver and 5 times higher in the spleen of mice fed H-La or H-Sa as compared with those of the control group. These results suggest that the sterilizing function of fixed macrophages both in the liver and the spleen was suppressed in mice fed H-La or H-Sa.
Two ester-type prostaglandin oligomeric compounds were synthesized, one from prostaglandin E1 (termed MR-356) and the other from prostaglandin B2 (termed OC-5186). Using in vivo [31P]MRS, the protective effects of these oligomers on forebrain ischemia (15 min) were evaluated in a rat model. Forebrain ischemia caused a decrease in intracellular high energy phosphates and intracellular pH (pHi) in the control and compounds-treated groups, but changes of these values in the OC-5186-treated group were significantly smaller than those in the control group. Moreover, the cerebral energy metabolism of the OC-5186-treated group returned to the preischemia level more rapidly than in the control group after forebrain ischemia. MR-356 had some effects, but the differences were not significant.
We treated 41 chronic hepatitis C patients with recombinant interferon alpha 2a, 6 X 10(6) IU/day, for three weeks daily followed by intermittent therapy, 3 X 10(6) IU/day, three times weekly for 6 months and more. After 6 months of intermittent therapy, serum aminotransferases (AST, ALT) decreased to normal or nearly normal levels in 29 of 41 patients (70.7%) with histological improvement. The HCV (C100-3) antibody disappeared during and after IFN therapy in 7 of 34 HCV antibody positive patients (20.6%). Serum aminotransferases levels of all such patients were normalized or nearly normalized. The IFN antibody was detected in 8 of 41 patients (19.5%) including one whose IFN antibody was already present before starting IFN therapy. IFN treatment was discontinued in 22 of 41 patients (53.7%) because they responded completely or nearly completely to IFN therapy. All of the 22 patients have been maintaining normal aminotransferase levels for 1 to 24 months (mean, 12 months) after the treatment period. We conclude that long-term IFN therapy is greatly beneficial in controlling hepatic inflammatory changes in chronic hepatitis C.
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The effect of human thrombomodulin (TM) on the inactivation of thrombin by human antithrombin III (ATIII) was evaluated in comparison with that produced from rabbits. Human TM did not accelerate the thrombin inhibition by ATIII but rabbit TM enhanced the activity of ATIII. Also inclusion of human TM at increasing concentration suppressed the thrombin inhibitory activity of ATIII. The intensity of ATIII activity in the presence of heparin (0.01U/ml) was also diminished by the human TM. However, this ATIII- heparin cofactor activity recovered with the addition of a 10-fold amount of heparin (0.1U/ml). In SDS-polyacrylamide gel electrophoresis and immunoblotting analysis, we found a complex formation of ATIII with both human and rabbit TM (and further confirmed their presence with isoelectrofocusing electrophoresis- data not shown). These results indicate that human TM is substantially different from rabbit TM. Our results suggest that human TM show the crucial role on protein C activation system via thrombin.
The optimal time of intravenous lidocaine for attenuation of pressor responses to laryngoscopy and endotracheal intubation was evaluated in fifty adult patients and the correlation between plasma lidocaine level and its clinical effects were also studied. The plasma lidocaine levels were highest 0.5 min after administration of lidocaine 1.5 mg.kg(-1) intravenously. However, endotracheal intubation 0.5 min after lidocaine administration caused significant increase in mean arterial pressure (MAP) and heart rate (HR). Mean arterial pressure and HR increased with endotracheal intubation following 1, 2 and 3 min after lidocaine administration, but the magnitude of increase was not statistically significant. There were no significant differences in MAP changes among these three groups. It was concluded that the plasma lidocaine levels did not correlate with its suppressive effect on circulatory responses due to laryngoscopy and endotracheal intubation. Laryngoscopy and endotracheal intubation should be carried out at least 1 min after intravenous lidocaine administration.
1. Serum cholesterol levels in Japan were unrelated to total fat intake and its quality. 2. A significant positive correlation was found between serum cholesterol level and BMI, and the total energy intake was significantly higher in hypercholesterolemic group than in normocholesterolemic group. 3. Hypercholesterolemia seems to occur in the background of accumulation of body fat due to relative excess of energy intake in Japan.
The present study dealt with two objects; the first object was to examine whether or not lithium uptake in thyroid is modified by the thyroid state and how the intrathyroidal Li affects iodide uptake by the thyroid. Male and female mice were given lithium carbonate (Li) with propylthiouracil (PTU) or thyroxine (T4). Li was measured by a flameless atomic absorption spectrometry. The total Li content in thyroid was unaffected with PTU or T4, however, Li concentration per unit mass was reduced by PTU but unaffected by T4. The thyroid: serum ratio (T/S) of 125I resulted that the T/S became higher when Li concentration per unit mass was lower and vice versa, suggesting that Li uptake is controlled by thyroid states and Li in the gland interferes with the iodide uptake. Serum triiodothyronine (T3) and T4 by radioimmunoassay showed that PTU alone and in combination with Li lowered serum T4, while a high level of T4 by its supplement was suppressed by co-administration of Li. T3 level was lowered by Li alone, but not severely affected by other drugs. The results suggest that Li enhances T4 clearance without T4-T3 conversion. The second object was to examine the effect of combined psychotropic drugs on thyroid function. Carbamazepine (CBZ), haloperidol (HLP) and imipramine (IPA) were given singly or in combination with Li to examine their effects on the T/S of 125I. Only CBZ reduced the T/S but CBZ plus Li had no summative effect. Neither HLP nor IPA affected the T/S, singly or in combination with Li, suggesting that HLP or IPA does not interfere with an iodide pumping machinery. No distinct sex difference was observed in drug effects.
It is known that antithrombin III (ATIII) activity is inhibited by tissue thromboplastin (TP) in the presence of heparin. In our study on the mechanism of the inhibition, however, TP was found to inhibit ATIII activity even in the absence of heparin, indicating an interaction between ATIII and TP. We then studied effect of ATIII on the interaction between factor VII (FVII) and TP using FVII-depleted human plasma. When the mixture of FVII + ATIII + TP was incubated at 37 degrees C and mixed with FVII-depleted plasma, the interaction between FVII and TP was inhibited. Possible complex formation was examined by electrophoretic techniques. In the immunoelectrophoresis, ATIII shifted toward the cathode in the presence of TP and the substance which had changed the mobility of ATIII showed TP activity after zone electrophoresis. The results indicated that TP had shifted toward the anode due to ATIII while ATIII had shifted toward the cathode due to TP. In the immunoblotting analysis, ATIII was separated into several bands in the presence of TP. ATIII antigenicity was altered in the presence of both heparin and TP but not in the presence of TP alone. Our results strongly suggest that TP modulates ATIII activity in the initiation of the TP-mediated coagulation cascade and that in progressing coagulation ATIII participates in the inhibition of the coagulation cascade by blocking not only thrombin activity but also the interaction between TP and FVII.
The synergistic effect of antithrombin III (ATIII), activated protein C (APC) and heparin on the tissue thromboplastin (TP)-mediated coagulation cascade was studied. APC prolonged the activated partial thromboplastin time of human plasma with increasing APC concentration but affected the prothrombin time only slightly. Neither ATIII nor heparin prolonged the prothrombin time by itself, while a mixture of APC and heparin strongly inhibited the coagulation. When the effects of APC, heparin and ATIII on the TP-mediated coagulation were examined with a solution consisting of prothrombin, factor V, factor VII, factor X and fibrinogen at physiological concentrations, the coagulation time was prolonged only slightly by the APC-heparin or ATIII-heparin mixture. However, the coagulation time was prolonged markedly by simultaneous addition of APC, ATIII and heparin to the solution. Inhibition of thrombin activity by the ATIII-APC-heparin mixture was weak as compared with that by the ATIII-heparin mixture after a 1-min incubation, but after a 2-min incubation the inhibitory activities were equal. Suppression of thrombin activity by the ATIII-APC-heparin mixture was supposed to be due to the inhibition of the interaction between ATIII and heparin on thrombin by APC because the APC-ATIII-heparin complex was detected by crossed immuno-electrophoresis but not by sodium dodecyl sulfate (SDS)-polyacrylamide electrophoresis. When the inhibitory effect of APC alone or the APC-heparin mixture on the platelet prothrombin converting activity (PPCA) was examined, heparin accelerated the PPCA inhibition by APC.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of continuous prostaglandin E1 (PGE1) infusion 0.03 micrograms.kg-1.min-1 on hemodynamics, body temperature and urine output during cardiopulmonary bypass (CPB) were studied. Systemic vascular resistance was kept significantly lower in PGE1 administration group than control group. Differences between core and peripheral temperature decreased faster in the PGE1 administration group than the control group. Mean arterial pressure was stable at 40mmHg during CPB in the PGE1 group and 60mmHg in the control group. However, there were no significant differences in urine output between the PGE1 administration group (10.8ml.kg-1.h-1) and the control group (9.4ml.kg-1.h-1). This study indicates that continuous PGE1 infusion (0.03 micrograms.kg-1.min-1) is a method of choice for vasodilation and improvement of peripheral perfusion during hypothermia of CPB.
Since the preliminary analyses of the glycolipids of small cell carcinomas of the lung showed an increase of GM2 ganglioside, we generated new murine monoclonal antibodies directed to GM2 to identify the molecular species of the glycolipid. The monoclonal antibodies MK2-34 and MK1-16 (both IgM), which specifically detect N-glycolyl GM2 and N-acetyl GM2, respectively, were generated by immunizing mice with liposomes containing monophosphoryl lipid A, trehalose dimycolate, and the antigenic ganglioside. Among the glycolipid preparations extracted from the cancer tissues of 39 patients with lung cancer, a significant amount of N-acetyl GM2 was detected with MK1-16 antibody in 70% of the squamous cell carcinoma cases, 50% of the lung adenocarcinoma cases, 33% of the large cell carcinoma cases, and 100% of the cases of small cell carcinoma of the lung. On the other hand, N-glycolyl GM2 which was defined by the monoclonal MK2-34 was not found in any of the glycolipid fractions prepared from the lung cancer tissues examined in this study. Immunohistochemical studies of the lung cancer tissues with the MK1-16 antibody showed that the N-acetyl GM2 was present not only in small cell carcinoma tissues as one of the antigens related to tumors of neuroectodermal origin, but also in the squamous cell carcinoma and adenocarcinoma of the lung with a comparable frequency. The appearance of the N-acetyl GM2 antigen correlated well with the degree of differentiation of the cancer cells in patients with squamous cell carcinoma and adenocarcinoma of the lung.
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