[A case of autoimmune hemolytic anemia, interstitial pneumonia and liver injury occurred during one month's medication of small dose of alpha-methyldopa].
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Aged↗
Biomedical subjects
M Ueda
Publications and source records attributed to M Ueda.
Effects of divalent cations on the regulation of insulin-sensitive glucose transport and cAMP phosphodiesterase in adipocytes. Insulin-like effects of divalent cations.
Effects of divalent cations on the regulation of glucose transport and cAMP phosphodiesterase in isolated rat epididymal adipocytes were studied. EDTA (5 mM) moderately inhibited the binding of insulin to adipocytes in Krebs-Henseleit Hepes buffer. In the same buffer, A-23187 (an ionophore specific for divalent cations; 50 microM) plus EDTA (5 mM) almost completely blocked the insulin- or hydrogen peroxide-dependent stimulation of phosphodiesterase. This inhibition was not secondary to the loss of ATP. When cells that had been treated with A-23187 plus EDTA were washed and then exposed to 1-10 mM of divalent cations, the cellular phosphodiesterase activity was elevated. Mn2+ was most stimulatory, Mg2+ was next, and Ca2+ was least effective. The stimulatory effects were enhanced by insulin. In the presence of insulin, Mn2+ at 10 mM was less stimulatory than that at 1 mM. In regular Krebs-Henseleit Hepes buffer, Mn2+ greatly stimulated phosphodiesterase if cells were first exposed to A-23187. The Mn2+-dependent stimulation was blocked by treatment of cells with 2,4-dinitrophenol. Results essentially parallel to those described above were also obtained when the rate of glucose transport was determined. The above results indicate that divalent cations mildly support the extracellular binding of insulin to its receptor, facilitate the physiological actions of insulin, and mimic the hormone actions, presumably by stimulating an intracellular enzyme.
2,4-Dinitrophenol↗
Isolation of human erythropoietin with monoclonal antibodies.
Human erythropoietin was isolated from urine of aplastic anemic patients in a high yield with a simple purification procedure using an immunoadsorbent column of monoclonal antibodies and a Sephadex G-100 column. About 6 mg of erythropoietin was isolated from 700 liters of urine and the specific activity was estimated to be 81,600 units/mg of protein with an in vivo 59Fe incorporation assay method, using starved rats. Activity measurement of the extracts from sliced gels after sodium dodecyl sulfate-polyacrylamide gel electrophoresis and the Western blotting technique revealed heterogeneity of the isolated erythropoietin, which is probably caused by variable amounts of carbohydrates attached to the polypeptide chain. Thirty amino acids in the NH2-terminal portion of the isolated hormone were sequenced.
Anemia, Aplastic↗
Characterization of peroxisomal and mitochondrial carnitine acetyltransferases purified from alkane-grown Candida tropicalis.
Properties of peroxisomal and mitochondrial carnitine acetyltransferases purified from an alkane-grown yeast, Candida tropicalis, were compared each other. The molecular weight of both enzymes was estimated to be about 420 000 by analytical ultracentrifugation and gel filtration chromatography with Sepharose 6B. However, each enzyme gave two subunits on the polyacrylamide slab gel electrophoresis in the presence of sodium dodecyl sulfate: the peroxisomal enzyme (64 000 and 57 000) and the mitochondrial enzyme (64 000 and 52 000). The subcellularly distinct enzymes gave a similar amino acid composition except for the contents of some amino acids: glycine, valine, glutamic acid and aspartic acid. Their isoelectric point was somewhat different: 5.11 for the peroxisomal enzyme and 5.22 for the mitochondrial enzyme. Both enzymes had the same amino-terminal residue (glutamic acid or glutamine) and the heat stability, and was indistinguishable immunochemically. These results suggest that peroxisomal and mitochondrial carnitine acetyltransferases of C. tropicalis cells may be products of the same nuclear gene. Differences in the molecular weight of the subunits of the enzymes would result from modification or processing of the common protein in the step of distribution to the respective organelles, that is, so-called post-translational modification.
Acetyltransferases↗
Synthesis in vitro of precursor-type carnitine acetyltransferase with messenger RNA from Candida tropicalis.
Carnitine acetyltransferase was synthesized in vitro in the mRNA-dependent reticulocyte system with mRNA from alkane-grown or propionate-grown cells of Candida tropicalis. The protein synthesized in vitro was isolated by immunoprecipitation with antibody against peroxisomal or mitochondrial carnitine acetyltransferase and was compared with peroxisomal carnitine acetyltransferase (Mr of subunits, 64 000 and 57 000) and the mitochondrial enzyme (Mr of subunits, 64 000 and 52 000) of C. tropicalis by electrophoresis in the presence of sodium dodecyl sulfate. Nascent carnitine acetyltransferase prepared in vitro showed a hetero-oligomeric property, like the peroxisomal and mitochondrial enzymes isolated from C. tropicalis. The molecular weights of the subunits of nascent carnitine acetyltransferase were estimated to be 71 000 and 57 000, indicating the existence of the precursor form of the enzyme. By sucrose density gradient centrifugation of total mRNA, these two subunit proteins were shown to be synthesized with respective mRNAs of different sizes. The same precursor-type of carnitine acetyltransferase was obtained with the mRNAs from the alkane-grown cells and the propionate-grown cells. The results obtained suggest that a common precursor will be post-translationally modified to form the peroxisomal and mitochondrial enzymes.
Acetyltransferases↗
Relation of clinical activity of rheumatoid arthritis to immune complexes, complement components and anti-immunoglobulins.
Circulating immune complexes by fluid phase Clq binding assay, complement components and anti-immunoglobulin levels were studied in sera of 35 patients with rheumatoid arthritis (RA). In 23 of the 35 sera (65.7%), circulating immune complexes were positive, and the mean +/- SD of Clq binding activity (ClqBA), 44.5 +/- 19.4%, was significantly high compared to that of healthy persons, 17.4 +/- 8.2%. Antigenic determination of complement components revealed that Clq, C3, C5, C9, factor B and Cl esterase inhibitor (ClINH) were significantly high in sera of RA, but C4 and properdin were not. The disease activity correlated with ClqBA, IgG- and IgM-anti-immunoglobulins, C9 and serum IgG. On the other hand, ClqBA correlated with both IgG- and IgM-anti-immunoglobulin levels but not with complement components.
Adolescent↗
C3b receptor (CR1) on erythrocytes in various diseases.
Complement receptor for C3b (CR1) on erythrocytes was investigated in various diseases by immune adherence hemagglutination (IAHA) using aggregated human IgG. In normal controls, 21 out of 312 (6%) revealed defective CR1 reactivity, and there was no difference in the prevalence of defective CR1 reactivity between female (11/157, 7%) and male (10/155, 6%). Among diseases examined significantly high prevalence of defective reactivity of CR1 on erythrocytes was seen in systemic lupus erythematosus (SLE) (22/30, 73%) and malignancy of hematopoietic system, especially in acute myelogenous leukemia (AML)(6/11, 55%).
Connective Tissue Diseases↗
Effects of irradiation of skin flaps.
The reaction of skin flaps to irradiation and the optimum postoperative time for irradiation was studied in the rat. Flaps showed different reactions depending on the time of irradiation. There was a correlation between the radiosensitivity and the vascularity of the flap. Those flaps in the marginal hypovascular stage of revascularization showed reactions similar to normal skin. However, severe adverse reactions were observed in the marginal hypervascular stage.
Angiography↗
Experimental study of dermal grafts for reconstruction of oral mucosa.
Mucosal defects in the oral cavities of 35 dogs were repaired with reversed dermal grafts, full-thickness skin grafts, and dermal grafts. Comparative observations were made for up to two years to analyze the healing processes. The reversed dermal grafts were covered by surrounding mucosal epithelium and formed normal mucosal tissue that maintained its characteristics for two years. Histologic and scanning electron microscopic examination revealed that the epithelial appendages underwent degeneration, presumably through being embedded by the grafting of the dermis inside out. Epithelialization of the dermal grafts occurred from both surrounding mucosal epithelium and ancillary skin appendages. The full-thickness skin grafts maintained their original structure and function over the two-year observation period. It appears from this investigation that the reversed dermal graft method has definite advantages over full-thickness skin grafting and dermal grafting.
Animals↗
Dynamic vascular changes in free skin grafts.
Vascular changes in full-thickness skin grafts in rats were examined at various intervals after grafting using microangiography. The grafted skin and its bed showed dynamic vascular changes that were considered to be related to release of an " angiogenetic factor" produced by the skin under oxygen-deficient conditions such as ischemia. The first filling of contrast medium in the grafts was observed 24 hours after grafting. Both primary and secondary revascularization were observed.
Angiography↗
Synthesis and antiarrhythmic activity of new 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1 H-imidazoles and related compounds.
Various 1-[1-[2-[3-(alkylamino)-2-hydroxypropoxy]phenyl]vinyl]-1 H-azoles were synthesized and investigated for beta-adrenoceptor-blocking and antiarrhythmic activities. Although no compounds showed more potent beta-blocking effects than propranolol in the isolated guinea pig right atria, many compounds exhibited significant antiarrhythmic effects against aconitine or ischemic arrhythmia in mice or dogs. 1-[2,5-Dichloro-6-[1-(1H-imidazol-1-yl)-ethenyl] phenoxy]-3-[(1-methylethyl)amino]-2-propanol hydrochloride (48) (711389-S) was selected as a candidate for clinical evaluation in man, since its antiarrhythmic effects were superior to those of quinidine, disopyramide, or propranolol. Asymmetric synthesis of (R)-(+)- and (S)-(-)-48 is described, and it is proven that there is no stereospecificity in the antiarrhythmic effect of 48.
Adrenergic beta-Antagonists↗
T lymphocyte reconstitution in long-term survivors after allogeneic and autologous marrow transplantation.
T cell subsets and their immune reactivities were studied in long-term survivors after bone marrow transplantation and the results of autotransplanted and allotransplanted patients were compared. These two groups of patients (4 autotransplants and 4 allotransplants) were roughly comparable in terms of their underlying diseases, pretransplant conditioning regimens, supportive care, and posttransplant sampling days for immunological studies. Significant differences were observed between autologous and allogeneic marrow recipients in the total number of OKT3-, OKT4-, OKT8-, and OKIa1 -positive cells. Similar differences were observed between transplant patients and normal controls. Decreased OKT4 cells and increased OKT8 cells resulted in inversion of the OKT4:OKT8 ratio, which was significantly lower in allotransplanted compared with autotransplanted patients, and both groups of transplant patients showed depressed responses in comparison with normal controls. In contrast, there were no significant differences in MLR reactivities between transplanted patients and normal controls. When mitogenic responses were analyzed in relation to T cell subsets, phytohemagglutinin responsiveness showed a significant correlation with OKT4:OKT8 ratios (P less than 0.01) and the proportions of cultured OKT4 cells (P less than 0.01). These observations suggest that T lymphocyte reconstitution is still incomplete or abnormal in long-term survivors regardless of the type of graft. Furthermore, abnormalities observed in these long-term survivors were characterized by an imbalance of T cell subsets that was more profound in allotransplanted than in autotransplanted patients.
Adolescent↗
Physiological characterization of influenza virus temperature-sensitive mutants defective in the haemagglutinin gene.
We have characterized the physiological defect in two temperature-sensitive mutants of the WSN strain of influenza virus which possessed a lesion in the haemagglutinin (HA) gene. In mutant virus-infected cells at the non-permissive temperature, the precursor HA polypeptide containing predominantly mannose-rich carbohydrate chains was not converted to the mature, functional HA polypeptide. Immunofluorescence showed that the HA polypeptide did not appear on the cell surface but was confined largely to the Golgi apparatus. It was concluded that the major physiological defect of these mutants was a block in the transport of the HA polypeptide beyond the Golgi apparatus. The block could be reversed, however, by lowering the temperature to 34 degrees C, resulting in normal processing of the precursor polypeptide and emergence of infectious progeny virus within 30 min. The HA activity of the two mutants, but not wild-type virus, was rapidly inactivated at 51 degrees C. Most, but not all, revertants derived from these mutants had HA with the heat stability of wild-type virus, suggesting that the temperature sensitivity and the heat lability of HA were two pleiotropic manifestations of a single lesion in the HA gene.
Animals↗
[Analysis of chronic subdural hematoma based on CT (Part III). Clinical stage classification based on CT findings].
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Adult↗
[Pharmacological studies of a new sleep-inducer, 1H-1,2,4-triazolyl benzophenone derivative (450191-S) (V). General pharmacological activities].
General pharmacological activities of 450191-S were studied in various species of animals and compared with those of reference benzodiazepines (BDZ). 450191-S at doses of 10 mg/kg slightly decreased (-5 degrees C) the rectal temperature of rabbits. 450191-S decreased respiratory and heart rates in anesthetized cats, but the effects were less than those of diazepam or triazolam. 450191-S increased respiratory and heart rates in conscious dogs, but had no effect on the blood pressure, electrocardiogram and autonomic nervous system in cats and dogs. The drug displayed a slight spasmolytic activity in the small intestine of guinea pigs and a slight inhibitory effect on isolated non-pregnant and pregnant uteri of rats. These effects were less than those of diazepam or nitrazepam. Below doses of 25 mg/kg, 450191-S did not affect urinary volume and electrolyte excretions in rats. It also decreased brain norepinephrine (NE) turnover rates in rats, but decreased NE and dopamine turnover rates in mice. These effects of 450191-S were less than those of nitrazepam. 450191-S was found to be minimally irritating to the ocular mucosa in rabbits and did not irritate the stomach and small intestine in rats. These effects were also compared with those of active metabolites of 450191-S, M-1, M-2, M-A, M-3 and M-4, and the superiority of the mother compound over its metabolites was clarified.
Animals↗
[Peplomycin sensitivity of various types of human gynecological cultured tumor cells].
Various types of human gynecological cultured tumor cells were tested for the sensitivity to Peplomycin (PEP), an effective antitumor antibiotic for squamous cell carcinomas, by the regrowth assay method together with morphological observation. Bleomycin-hydrolase activity of these cell lines was also compared in cell-free extracts by assaying the conversion of Bleomycin into its deamidated from (HPLC method). SKG-I, SKG-II, SKG-IIIb cells derived from squamous cell carcinoma of the cervix and RKN cells derived from myosarcoma of the ovary were much more sensitive to PEP than other cell lines. PEP was found to be mainly a time-dependent drug, but also concentration dependent. The effect of PEP on cell morphology was characterized by the appearance of enlarged cells and swelling nuclei. The specific activities of Bleomycin-hydrolase in SKG-I, SKG-II, SKG-IIIb cells were shown to be relatively lower than that in other cell lines. These results suggested that cervical squamous carcinoma cells and ovarian myosarcoma cells were sensitive to PEP and Bleomycin-hydrolase activity was one of factors which decided the PEP sensitivity of human cultured tumor cells.
Antibiotics, Antineoplastic↗
Effect of activated lymphocytes on the regulation of hematopoiesis: suppression of in vitro granulopoiesis by OKT8+Ia+T cells induced by alloantigen stimulation.
We studied the effects of alloantigen-stimulated lymphocytes in the regulation of hematopoiesis. Alloantigen-stimulated lymphocytes were harvested on days 2 to 3, days 6 to 7, or days 9 to 10 of MLC and were tested for their effects on granulocyte/macrophage progenitor cells (CFU-C). Dose-dependent suppression of CFU-C was observed when alloantigen-stimulated lymphocytes from days 6 to 7 and days 9 to 10 MLC were added to the cultures of autologous or allogeneic bone marrow cells for CFU-C assays. Suppressive activity was detected in the T cell fraction but not in the non-T cell fraction. For further characterization of these CFU-C/suppressor cells, alloantigen-stimulated lymphocytes were treated with radiation (2000 rad) or with monoclonal antibodies against T cell subsets and complement (C) before culture. Suppressive activity was completely abolished by treatment with OKT8 or OKIa1 antibodies and C whereas suppression was retained after radiation treatment. These observations suggest that CFU-C/suppressor cells can be induced by alloantigen stimulation in MLC and that they are radioresistant OKT8+ and Ia+ T cells.
Antibodies, Monoclonal↗
[Plasminogen activator inhibitor activity of cultured normal human fibroblasts].
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Cells, Cultured↗