[Chou-Fasman's prediction of the secondary structure of proteins with a hand-held computer].
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Biomedical subjects
Publications and source records attributed to M Tamura.
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Gestational and postnatal changes of microsomal NADH:cytochrome b5 reductase and NADPH:cytochrome c reductase activities were examined in rat brain. The specific activity of NADH:cytochrome b5 reductase was high at 18-19 days of gestational age, decreased to a minimum at 4 to 6 days after birth and increased thereafter. An essentially similar developmental pattern was observed for the specific activity of NADPH:cytochrome c reductase. In contrast, the specific activities of these reductases in liver microsomes were low, did not display a peak during gestation and increased steadily to a maximum at 40-50 days after birth. The rate of incorporation of [2-14C]malonyl-CoA into palmitoyl-CoA in brain microsomes was found to be high in the foetus, sharply decreased to a minimum at the time of birth and increased thereafter. The activity of fatty acid elongation in liver microsomes was much less than that in brain during gestation and increased rapidly after birth to values at 50-60 days 20-fold greater than the foetal activity. NADH and NADPH were equally effective for brain microsomal fatty acid elongation. Regional distribution of cytochrome reductase activities and the activity of fatty acid elongation showed the lowest specific activity in cerebellum. These results suggest that brain microsomal electron transport may be correlated with the developmental alteration in fatty acid elongation.
Islet-activating protein (IAP), pertussis toxin, is an oligomeric protein composed of as A protomer and a B oligomer. IAP and its A protomer were equipotent, on a molar basis, in enhancing GTP-dependent adenylate cyclase activity and in causing ADP-ribosylation of the 41,000 Mr protein when directly added to the cell-free membrane preparation from rat C6 glioma cells. Similar actions of IAP observed upon its addition to intact C6 cells were not mimicked by its A protomer, indicating that the A protomer had to be associated with the B oligomer to become accessible to its site of action on the inner surface of the membrane of intact cells. The A protomer, but not IAP, exhibited NAD-glycohydrolase activity in the reaction mixture lacking cellular components but containing dithiothreitol. Their actions on membranes were not accelerated by dithiothreitol, but markedly suppressed by oxidized glutathione. Thus, C6 cell membranes may possess certain "processing" enzyme(s) responsible for releasing the A protomer from the IAP molecule and for reductive cleavage of an intrachain disulfide bond in the released protomer, thereby producing an active peptide which functions to cause ADP-ribosylation of one of the subunits of guanine nucleotide regulatory protein in the receptor-adenylate cyclase system.
Islet-activating protein (IAP), pertussis toxin, is an oligomeric protein (Tamura, M., Nogimori, K., Murai, S., Yajima, M., Ito, K., Katada, T., Ui, M., and Ishii, S. (1982) Biochemistry 21, 5516-5522), the biggest subunit (Mr = 28,000, referred to as the A-protomer) of which catalyzes transfer of the ADP-ribose moiety of NAD to the membrane Mr = 41,000 protein. The pentamer, termed the B-oligomer, consisting of the residual subunits was the moiety of IAP that was responsible for binding to the cell surface, as revealed by competitive inhibition of the development of the IAP actions on intact rat C6 glioma cells and rat adipocytes. The binding of the B-oligomer to its receptor proteins was divalent via the constituent two dimers; it stimulated mitosis of lymphocytes and caused an insulin-like action to enhance glucose oxidation in adipocytes, just as did concanavalin A, presumably as a result of cross-linking or aggregation of the membrane proteins. The A-promoter displayed its biological action on adipocytes only when the B-oligomer had been bound to the cells. Thus, IAP is a typical A-B toxin in which the B-oligomer is first bound to the cell surface proteins to enable the A-protomer to reach to the site of its action within the cell. Diverse biological actions of pertussis toxin may be accounted for by the mitogenic action of the B-oligomer as well as ADP-ribosyltransferase activity of the A-promoter.
Synthetic double stranded RNA (poly I: poly C) was prepared from polyinosinic acid (poly I) and polycytidylic acid (poly C) by heat-treated followed by gradual cooling, and was used for induction of human leukocyte interferon (IFN). When poly I: poly C solution was heated at 37 - 65 degrees C for 30 minutes, high activity of human IFN (10,000 - 60,000 i. u./ml) was obtained. In this system, the optimum molecular weight of poly I: poly C to induce IFN was 12.6 - 17.6 S. The properties of induced IFN were heat- and acid- stable, and it was neutralized with anti-IFN alpha serum. So, it was confirmed that it was IFN alpha.
Human erythrocytes were divided into age groups according to their density using phthalate esters as separating liquids. The concentration of cytochrome b5 and the activity of NADH-cytochrome b5 reductase decreased exponentially with the age of red cells. The apparent half-life of cytochrome b5 was estimated to be 44 days. The decline of cytochrome b5 seemed to be more rapid than the decline in the activities of glutamate-oxaloacetate transaminase and NADH-cytochrome b5 reductase whose apparent half-lives were 210 and 240 days, respectively. A biphasic decline of cytochrome b5 was observed on storage of erythrocytes at 4 degrees C. It was deduced from the kinetic results that the decrease of cytochrome b5 might be involved in the increase of the concentration of methemoglobin in senescent erythrocytes. Cytochrome b5 may be used as an indicator of mean red cell age.
The stopped flow and flash photolysis methods were applied for the kinetic study of the reaction of carbon monoxide with myoglobin in solution, in an amorphous state, and in crystals. From the flash photolysis data, the reactivity of myoglobin was concluded to be essentially the same in all three states. When the reaction was started with a stopped flow apparatus, the rate became slower as the state of myoglobin was changed from solution to amorphous precipitate, and to crystals. The bigger the crystals, the slower the reaction became. Therefore, the change of the rate could be explained in terms of a diffusion layer formed on the crystals. In the reaction of crystalline myoglobin, the effective concentration of CO was increased locally by about 20 microM after flash photolysis and approached the bulk concentration during the reaction. In contrast, in the reaction of amorphous precipitate of myoglobin, such an increase in the CO concentration was apparently dispersed homogeneously just after flash photolysis.
A case of Hodgkin's disease with amyloidosis in various organs in a 68-year-old Japanese man is reported. The initial sign was dysuria followed by diarrhea, melena, and ileus. There was no history of pulmonary tuberculosis or rheumatoid arthritis. Autopsy findings suggested that Hodgkin's disease may have been the initial disease in development of secondary systemic amyloidosis, followed by dysuria and paralytic ileus.
By measuring the absorbance change due to myoglobin oxygenation in hemoglobin-free isolated perfused rat hearts, we analyzed effects of perfusion pressure and heart rate upon the intracellular oxygen concentration. With Langendorff perfusion, the cardiac tissue was kept normoxic (above 50 microM O2) at aortic pressure above 50 cm H2O, but became hypoxic (8 microM O2) at 30 cm H2O. The increase in cardiac work, expressed as the product of peak systolic pressure and heart rate, increased oxygen consumption at aortic pressure of 50-200 cm H2O. The heart was kept normoxic under these conditions. Lactate release, oxygen consumption, and the oxidation-reduction state of pyridine nucleotide were measured as a function of myoglobin oxygenation under various normoxic and anoxic conditions. Pyridine nucleotide fluorescence and lactate release started to increase as the intracellular oxygen concentration decreased to 6 and 10 microM, respectively. Oxygen consumption was kept constant until the oxygen concentration decreased to 10 microM and slowed down below it. A close relationship between oxygen consumption and lactate release was observed. Infusions of epinephrine and norepinephrine under normoxic perfusion conditions increased cardiac work, oxygen consumption, and lactate release. More than 50% of myoglobin was then deoxygenated even under normoxic perfusion conditions. The increase in lactate release was ascribable to the increase in glycolytic flux caused by hypoxia. The change of pyridine nucleotide fluorescence by epinephrine was also explained by hypoxia in cardiac tissue.
Diffuse panbronchiolitis (DPB) is a disease with chronic inflammation exclusively located in the region of respiratory bronchioles. The pathologic features of the disease are characterized by thickening of the wall of the respiratory bronchiole with infiltration of lymphocytes, plasma cells and histiocytes, and extension of the inflammatory changes toward peribronchiolar tissues. In the advanced stage, secondary ectasia of proximal bronchioli may occur. These changes appear as diffusely disseminated small nodular shadows throughout both lungs on the chest roentgenogram. Obstructive respiratory functional impairment, occasional symptoms of wheezing, and also cough and sputum resemble the feature of emphysema, bronchial asthma, or chronic bronchitis, respectively. In the advanced stage, large amounts of purulent sputum and dilatation of proximal terminal conducting bronchioli resemble bronchiectasis. However, diffuse panbronchiolitis belongs to a distinctly different category from these diseases, and should be distinguished from them, because it may often show rapid progression with fatal outcome. The disease is dominant in males and the onset is unrelated to age. More than 1,000 cases of probable diffuse panbronchiolitis and 82 histologically-confirmed cases have been collected in Japan.
A comparative study was made of ventilatory and airway occlusion pressure (P0.1; a parameter reflecting respiratory center output) responses to carbon dioxide between 11 patients with bronchial asthma and 10 chronic obstructive lung disease (COLD). Increments in ventilatory volume (VE) produced by a rise in end-tidal CO2 pressure (PETCO2), i.e. delta VE/BSA/delta PETCO2, were smaller in 4 patients with hypercapnic COLD than in 6 normal subjects. On the other hand, increments in P0.1 produced by an elevation of PETCO2 (i.e. delta P0.1/delta PETCO2) tended to be diminished in patients with hypercapnic COLD. Higher values for both VE/BSA and P0.1 were observed in 6 patients with normocapnic COLD, but the differences from corresponding control values failed to achieve statistical significance due to a large variance. In 11 patients with bronchial asthma without attack, VE/BSA elevated significantly at PETCO2 levels of 50 and 60 torr, but values of delta VE/BSA/delta PETCO2 were virtually same as those in normal subjects.
The theoretical equations for the CO2 dissociation curve derived by MOCHIZUKI et al. (1983) have made it possible to estimate the CO2 contents in blood at any PCO2 by putting the intra- and extracellular bicarbonate contents at a certain PCO2 into them. Moreover, according to their Haldane effect equation, the carbamate and bicarbonate contributions are evaluated, when the Haldane effect and its plasma component are known along the PCO2 range. In order to accomplish the above calculation the water shifts due to the PCO2 and O2 saturation changes were measured as the changes of hematocrit. The hematocrit of oxygenated blood was linearly correlated to pH with a factor of -0.037, and the difference in hematocrit between oxygenated and deoxygenated bloods was 0.004 in terms of fractional hematocrit. The blood and plasma CO2 contents measured at four different PCO2's were compared with the ones calculated by use of the intra- and extracellular bicarbonate contents at 42 Torr PCO2. The measured and calculated CO2 contents coincided fairly well with each other. Using intra- and extracellular bicarbonate contents in oxygenated blood together with the Haldane effect and its plasma component, the carbamate contribution was then calculated. The carbamate content was about 1.2 mmol/liter blood over a PCO2 range of 20 to 100 Torr, and its ratio to the total Haldane effect decreased from 50 to 40%, as PCO2 was increased. The ratio of the bicarbonate shift to the total bicarbonate change due to the Haldane effect, ranging from 0.82 to 0.66, was significantly greater than that measured by changing PCO2.
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The pharmacokinetics of intravenously administered cefotiam (CTM), using a two-compartment or three-compartment open model, have been investigated in patients undergoing thoracic surgery. Patients (Group 1) given 1 hour drip infusion of 1 g of CTM, had the peak serum level (32.8 micrograms/ml) at 1 hour, and the peak pleural effusion level (8.3 micrograms/ml) was achieved at 2.08 hours. Patients (Group 2) given an one-shot intravenous injection of 1 g of CTM, had the maximum pleural effusion concentration (8.35 micrograms/ml) at 2.67 hours. Patients (Group 3) given 1 hour drip infusion of 1 g of CTM, had the mean concentration (2.3--2.5 micrograms/g) in the pleural tissue for 2 to 3.5 hours. Clinical study comprising 20 patients was performed to evaluate the effects of CTM as a prophylactic antimicrobial agent in the thoracic surgery. Patients received intravenous administration of 4 g/day of CTM for 7--10 days. Each patients was evaluated daily for fever, signs of allergic reaction, and wound infection and so on. No infections occurred in these thoracic surgery except 1, and no serious side effects was observed in this study.
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