Pure red cell aplasia caused by chlormadinone.
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Biomedical subjects
Publications and source records attributed to K Fukuda.
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We examined the distribution of alpha-, beta I-, beta II- and gamma-subspecies of protein kinase C (PKC) in the monkey visual pathway, including the retina, the lateral geniculate nucleus (LGN) and the visual cortex (area 17). In the retina, alpha-PKC immunoreactivity was found in cone photoreceptor and in bipolar cells. beta I-PKC immunoreactivity was present in the ganglion cell layer and the optic nerve fibers. The beta II- and gamma-PKCs were not found in the retina. In the LGN, intense gamma-PKC immunoreactivity was found in a part of magno and parvo cells. The LGN was negative for the alpha-, beta I- and beta II-PKC. All four PKC subspecies were present in the visual cortex but the distribution was distinct. The beta I-PKC immunoreactive cells were scattered in all layers, while the alpha-PKC immunoreactive cells were prominent in layers II, III, IVb, IVc and VI, and the beta II-PKC immunoreactive cells were found in layers II, III, IVb and VI. The intense gamma-PKC immunoreactivity was present in the neuropils in layers I, IVa, IVc and VI and also in soma and dendrites in layers II and VI. It thus seems likely that each subspecies plays a specific role in neuronal transmission in the visual pathway.
Protein kinase C (PKC) has attracted wide attention as a key enzyme for the expression of long-term potentiation in the hippocampus, a basic model for memory. It is of interest to study the detailed localization of PKC subspecies in the monkey hippocampus. We used immunocytochemistry to examine the localization of PKC subspecies in the hippocampus of the monkey, Macaca mulatta. Subspecies of PKC in the monkey could be separated by hydroxyapatite chromatography and the elution profile proved to be similar to that of the rat. Antibodies against each alpha, beta II and gamma-subspecies of the rat specifically reacted with the respective subspecies of monkey PKC. The alpha-, beta II- and gamma-subspecies were distinctly distributed in the hippocampus. The beta I-subspecies was not evident in the hippocampus. While both the alpha- and gamma-subspecies immunoreactive pyramidal cells were distributed throughout the hippocampus (CA1-CA3), the beta II-subspecies immunoreactive cells were scattered only in the CA1 region. The gamma-subspecies was found in granule cells and dendrites in the dentate gyrus, in mossy fibers and in their terminals in the CA3 region. The alpha-subspecies was also present in granule cells and in the dendrites but not in the mossy fibers. Glial cells did not stain with any of the antibodies used. Electron microscopy clearly showed that the gamma-subspecies was localized in both presynaptic terminals and post-synaptic dendrites. These observations suggest that subspecies of PKC in the monkey hippocampus may be involved in distinct functions and that the gamma-subspecies of PKC may act pre- and post-synaptically in pyramidal cells of the hippocampus.
From December, 1990 to July, 1992 we investigated the relationship between the time after oral food intake and nausea and vomiting caused by the intravenous injection of iodinated contrast media in 2,414 patients who underwent contrast enhanced CT. The contrast media used were as follows: amidotrizoic acid (high-osmolality contrast medium, HOCM, iodine 292 mg/ml) in 1173 patients, iopamidol (low-osmolality contrast medium, LOCM, iodine 300m g/ml) in 641 patients, and iohexol (LOCM, iodine 300 mg/ml) in 600 patients. All the patients had an intravenous injection of 100ml in volume. The overall incidence of nausea and vomiting was 3.8% (96/2412 patients). The incidence was 6. 7% (79/1173 patients) in the HOCM group and 1.4% (17/1241 patients) in the LOCM group. The incidence of nausea and vomiting increased with the interval between the oral intake of food and the intravenous injection of contrast medium. It is concluded that fasting before contrast-enhanced CT enhances the adverse effect of nausea and vomiting.
We have cloned a cDNA for a novel member of the opioid receptor family, designated as ROR-C, from the rat cerebrum cDNA library using the probe derived from the delta-opioid receptor subtype cDNA. The deduced amino acid sequence of ROR-C shows high homology with those of ROR-A (rat delta-opioid receptor subtype), ROR-B (rat mu-subtype) and ROR-D (rat kappa-subtype). RNA blot hybridization and in situ hybridization analysis revealed that ROR-C mRNA is expressed in discrete regions of the rat central nervous system.
Platelets activated by various agonists produce vesicles (microparticles; MPs) from the plasma membrane. However, the mechanism of this MP formation remains to be elucidated. To investigate the possible involvement of protein phosphorylation and cytoskeletal reorganization in MP formation, the effects of various inhibitors on MP formation were investigated. Flow cytometry was employed to detect the amount of MP formation by using monoclonal antibodies against glycoprotein (GP) IIb-IIIa (NNKY 1-32) or GPIIb (Tab). The relationship between changes in cytoskeletal architecture and MP formation in the platelets activated by thrombin plus collagen was observed by scanning electron microscopy (SEM). MPs were observed in the vicinity of the terminals of pseudopods, suggesting that MPs may be related by budding of the pseudopods. Cytochalasin D (10 microM) inhibited MP formation from the activated platelets almost completely. Moreover, SEM of the cytochalasin D-treated platelets revealed the absence of shape change, pseudopod formation and MPs. These findings suggest that cytoskeletal reorganization is necessary for MP formation. Since cytoskeletal reorganization is considered to be regulated by a dynamic phosphorylation-dephosphorylation process, we investigated the effects of the protein phosphatase inhibitors, calyculin A (CLA) and okadaic acid (OA), on MP formation. Flow cytometry showed that these two inhibitors doubled MP formation in activated platelets. SEM of the platelets treated with CLA or OA demonstrated more prominent shape change and pseudopod formation in these platelets than in those without inhibitor. From these results, we conclude that cytoskeletal reorganization, which is controlled by phosphorylation, is involved in MP formation.
Water-soluble ingredients of the herbal medicine sho-saiko-to dose-dependently inhibited the proliferation of a human hepatocellular carcinoma cell line (KIM-1) and a cholangiocarcinoma cell line (KMC-1). Fifty % effective doses on day 3 of exposure to sho-saiko-to were 353.5 +/- 32.4 micrograms/ml for KIM-1 and 236.3 +/- 26.5 micrograms/ml for KMC-1. However, almost no suppressive effects were detected in normal human peripheral blood lymphocytes or normal rat hepatocytes. Sho-saiko-to suppressed the proliferation of the carcinoma cell lines significantly more strongly than did each of its major ingredients, i.e., saikosaponin a, c, and d, ginsenoside Rb1 and Rg1, glycyrrhizin, baicalin, baicalein, and wogonin, or another herbal medicine, juzen-taiho-to (P < 0.05 or 0.005). Because such ingredients are barely soluble in water, there could be synergistic or additive effects of the ingredients in sho-saiko-to. Morphological, DNA, and cell cycle analyses revealed two possible modes of action of sho-saiko-to to suppress the proliferation of carcinoma cells; (a) it induces apoptosis in the early period of exposure and (b) it induces arrest at the G0/G1 phase in the late period of exposure.
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Close correlation between tissue transglutaminase (tTG) induction and growth regulation and/or cell death processes has been suggested in many cell lineages. In this study, the regulation of the tTG levels by various growth and differentiation factors and its relation to growth rate and cell death processes were investigated in two rat hepatoma cell lines, McA-RH7777 and McA-RH8994, using a monoclonal antibody against liver tTG. Transforming growth factor-beta 1 (TGF-beta 1) and retinoic acid (RA) each increased tTG to the level of 8- to 32-fold above that of control cultures in both cell lines after 72-h treatment. Dexamethasone (DEX) induced a 16- to 32-fold of tTG in McA-RH8994 cells while it did not change the enzyme level in McA-RH7777 cells. Simultaneous addition of DEX and RA increased the tTG level to more than 50-fold in McA-RH7777 cells as well as McA-RH8994 cells. Other factors, such as TGF-alpha, hepatocyte growth factor, dimethyl sulfoxide, and protein kinase C activator, did not show significant increases of the tTG levels. Although tTG induction by TGF-beta 1 or DEX appeared to be correlated with their growth suppressive effects, RA increased the tTG level without suppressing the growth rate of hepatoma cells. TGF-beta 1 was also shown to induce cell death in both cell lines. Our results demonstrate that RA and DEX are capable of modulating the TGF-beta 1-induced cell death processes independent of the tTG levels. We present evidence here that tTG induction by itself is not the direct cause of growth suppression and cell death in these hepatoma cells.
Human papillomavirus (HPV) types 16 and 18 are most prevalent in cervical carcinomas and are also present in metastatic sites. Thirty-six patients with lymph node metastases were examined for the possible presence of HPV 16 and 18 DNA sequences in the primary tumors as well as in metastatic lymph nodes. Polymerase chain reaction (PCR) analysis revealed the presence of the genome of HPV type 16 (HPV 16) in 17 tumors (47%) and that of HPV type 18 (HPV 18) in 2 tumors (6%), while 17 tumors (47%) were negative for both types. Of the 17 HPV 16-positive patients, 15 metastatic lymph nodes were also positive and 2 were negative. In 2 patients positive for HPV 18, the metastatic sites were negative. All the 17 patients negative for HPV in the primary tumors were also negative for HPV 16 and HPV 18 in the metastatic lymph nodes. These data confirmed the positive correlation of HPV DNA status between primary and metastatic tumors. However, the discrepancy in 11% of cases was attributed to presence of heterogeneous clones in the primary tumor.
The Kluyveromyces linear plasmids pGKL1 and pGKL2, encoding killer activity, were efficiently cured by UV irradiation. This event was investigated in more detail by the use of the terminal protein (TP)-associated cytoplasmic linear plasmids, pJKL1 and pRKL2, with a selectable marker LEU2. This observation was compared with the UV effect on the nuclear plasmids pLS1 (telomere-associated linear form) and YCp121 (centromere-integrated circular form), indicating that the UV hypersensitivity was specific to the cytoplasmic plasmids. Using rad4 and wild-type strains of S. cerevisiae, both pJKL1 and the nuclear plasmids were found to respond not only to photoreactivation repair but also to excision repair of UV-induced DNA damage. Thus these DNA repair systems were functional for both the nuclear and cytoplasmic plasmids in yeast, and it was suggested that the UV hypersensitivity of cytoplasmic plasmids might have been caused by a defect in other repair systems or in the TP-primed replication. Possibly TP-associated Debaryomyces linear plasmids were also UV hypersensitive.
Glucagon, a potent inducer of urea cycle enzymes, was administered subcutaneously, at a dose of 0.5 mg once a day, for 7 days to two citrullinemic patients. During this period, plasma NH3 levels in case 1 decreased significantly (P < 0.05 compared to levels before administration) and daily urinary excretion of urea N increased significantly (P < 0.05). For 1 week after the cessation of administration, the daily urinary excretion of urea N was significantly higher than the level before administration (P < 0.05), the plasma citrulline level during glucagon administration was lower than that before administration. In case 2, glucagon administration also decreased the plasma NH3 level (although the decrease was not statistically significant), and significantly increased daily urinary excretion of urea N (P < 0.05 compared to levels before administration). For 1 week after the cessation of glucagon administration the plasma citrulline level was significantly lower than that before administration (P < 0.05). These results indicate that glucagon significantly increases the urinary excretion of urea in the late onset form of argininosuccinate synthetase deficiency and that it may also decrease plasma NH3 levels in some patients with the deficiency.
Interleukin-1 (IL-1) is a key mediator in the pathogenesis of cartilage destruction in arthritis-related disorders. Human recombinant superoxide dismutase (SOD) blocked IL-1-mediated cartilage destruction but had no effect on IL-1-mediated changes in glycosaminoglycan and prostaglandin E2 synthesis. These data suggest that superoxide anions may be one factor of IL-1-mediated cartilage destruction.
The present study was conducted to evaluate the effect of potential risk factors--such as driving without a license, alcohol use, speed, seat belt, and helmet--use on fatality in motor vehicle traffic accidents. Unconditional multiple logistic regression analysis was employed to take these factors and age into account, simultaneously. The effect of driving without a license was not significant after controlling for other factors. The deleterious effect of alcohol use remained significant for male motorcar drivers after controlling for speed and seat belt use. Magnitude of the risk due to speed was slightly reduced after controlling for alcohol use and seat belt use, but the striking effect remained highly significant. Speed was the strongest risk factor of fatality for both motorcycles and motorcars and for both sexes and seemed to be more critical for motorcyclists than motorcar drivers. The protective effect of seat belt use was unchanged after adjustment for alcohol and speed, and the effectiveness of seat belt use was demonstrated for motorcar drivers. The effectiveness of helmet use for male motorcyclists was dependent upon speed at the time of the accidents, suggesting an interaction between helmet use and speed. Helmet use was definitely protective at a low speed of < or = 50 km/h, but ineffective at high speeds of over 50 km/h.
BACKGROUND/AIMS: To clarify the mechanism causing fatty liver in adult-type citrullinemia, the effect of fasting on blood levels of free fatty acids, triglycerides, and ketone bodies was investigated in two cases. METHODS: Blood and urine samples were collected from two patients and healthy volunteers 12, 15, 17, 21.5, and 24 hours after their last meal. RESULTS: During 24-hour fasting free fatty acid concentrations increased in both cases to the concentrations found in the healthy volunteers. The levels of blood ketone bodies (beta-hydroxybutyrate and acetoacetate) were markedly suppressed throughout the fasting test without any increase in urinary excretion of ketone bodies or organic acids in both cases when plasma citrulline concentrations were more than 10-fold higher than in controls. Serum triglyceride concentrations in case 1 paradoxically increased from 185 mg/dL to 294 mg/dL during 24-hour fasting when the citrulline concentration was extremely high. When hemodialysis was performed and plasma citrulline consequently decreased to near the normal level in case 1, levels of both serum triglycerides and blood ketone bodies responded normally to 24-hour fasting. CONCLUSIONS: These data suggest that ketogenesis was impaired in adult-type citrullinemia.
By in situ hybridization with digoxigenin-labeled RNA probes, distinct expression of mu opioid receptor mRNA was found in rat medullary preganglionic neurons for vagal parasympathetic outflow. Two days or more following unilateral vagotomy, the expression was almost completely abolished on the operated side. The results, taken together with previous findings indicating proximodistal axonal transport of radioligand-labeled opioid receptors, suggest that the medullary preganglionic neurons thus identified are the source for mu opioid receptor acting in cardiorespiratory and gastrointestinal tissues.
The frequency of occurrence and the characteristics of vascular mineralization in the brains of cows were studied. Mineralized lesions were found in the pallidal arteries in eight of 13 cows. They appeared as basophilic deposits in the arterial walls, were sheath-like or tubular in shape, and were accompanied by intimal oedema or fibrous thickening. The deposits were positive for periodic acid-Schiff, von Kossa's, alizarin red and Berlin blue stains. Elemental analysis revealed the presence of large amounts of phosphorus, calcium and zinc, as well as small amounts of iron, copper and sodium.
The renal mRNA expression of Na+/H+ exchanger (NHE) and the effects of NHE inhibitor, amiloride, on renal injury were investigated in adriamycin (ADR)-induced glomerulosclerosis model in rats, which progressively developed extensive glomerulosclerosis and interstitial fibrosis. NHE-1 mRNA from the cortex of the ADR rats progressively increased at weeks 4 and 8 and then peaked at week 16, which paralleled with the degree of glomerular sclerosis and interstitial fibrosis. The interstitial fibrosis in the ADR-rats was prevented by a daily administration of amiloride. A simultaneous analysis of the effects of a high salt diet on NHE-1 mRNA expression or renal injury was performed in the ADR rats at weeks 2 and 8. Renal or glomerular hypertrophy was observed in the control or ADR rats fed an 8% NaCl diet at week 2 and 8 compared to a 1% NaCl diet, while the NHE-1 mRNA expression was not up-regulated by an 8% NaCl diet at week 2. At week 8, the NHE-1 mRNA expression or glomerulosclerosis and interstitial fibrosis were enhanced in the ADR rats fed an 8% NaCl diet compared to a 1% NaCl diet. This histological aggravation by an 8% NaCl diet was prevented by a daily administration of amiloride but not by furosemide. In conclusion, the increased NHE-1 mRNA expression and the preventive effects of amiloride on the renal lesions suggest a potential importance of NHE in the progressive process of ADR-nephropathy. The high salt diet had a hypertrophic and destructive effect on kidney or glomeruli in the ADR rats.(ABSTRACT TRUNCATED AT 250 WORDS)