Increase in cyclic AMP level and stimulation of catecholamine synthesis in isolated bovine adrenal medullary cells caused by forskolin.
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Biomedical subjects
Publications and source records attributed to J Watanabe.
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Vitamin E is known to be an inhibitor of platelet prostaglandin production and aggregation. The rate of platelet aggregation induced by adenosine diphosphate was significantly increased in diabetics with proliferative retinopathy, and the enhanced production of thromboxane B2, a stable metabolite of thromboxane A2, was demonstrated in those patients. On the other hand, vitamin E was significantly reduced in platelets obtained from diabetics as compared to age matched control subjects. In addition, it was shown that vitamin E content in platelets examined in diabetic and control subjects inversely correlated with both the rate of platelet aggregation and thromboxane B2 production during aggregation. It is suggested that the reduced vitamin E levels in diabetic platelets can contribute to the mechanisms of the enhanced platelet thromboxane A2 production and aggregation which lead to the development of vascular complications.
Platelet aggregation is known to be increased in diabetes mellitus, and the enhanced thromboxane production has been shown to be one of the causes of such abnormal platelet function. To investigate which step is activated in diabetic prostaglandin metabolism, three specific inhibitors of prostaglandin synthetases were used in this study, which were mepacrine, indomethacin and imidazole. Platelet aggregation induced by collagen was significantly increased accompanying enhanced thromboxane production in diabetics with proliferative retinopathy compared with age matched controls. Platelet aggregation in diabetics with proliferative retinopathy was less inhibited by the addition of each inhibitor compared with controls. However, there was no difference in inhibitory pattern of platelet aggregation among the three inhibitors. In addition, thromboxane production during aggregation in diabetics with proliferative retinopathy was significantly greater than that in controls by the addition of each inhibitor. Inhibitory patterns of thromboxane production did not differ among the addition of three inhibitors. It is concluded that enhanced thromboxane production resulting in enhanced platelet aggregation would be related to diabetic vascular complications. This abnormal prostaglandin production can be due to the activation of general steps in prostaglandin metabolism in diabetic platelets, not of a specific enzyme.
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Monoclonal antibodies to membrane antigens of human small cell carcinoma of the lung were produced by fusion of P3X63/Ag8U1 mouse myeloma cells with spleen cells from BALB/c mice immunized against the intact cells of the small cell carcinomas grown in BALB/c nude mice. The hybrids were screened for antibody production using intact cells in a solid-phase radioimmunoassay or in a membrane fluorescence with a fluorescence-activated cell sorter. Four monoclonal antibodies were chosen that demonstrated reactivities with human small cell carcinoma of the lung and not with apparently normal diploid fibroblasts or lymphoblastoid cells. The antibodies designated as TFS-1 and TFS-2 rather demonstrated "pancarcinoma" reactivity, showing binding to the other types of lung cancer (adenocarcinoma, squamous cell carcinoma, and large cell carcinoma) and carcinomas derived from other organs, such as colon, pancreas, or stomach. The monoclonal antibodies TFS-3 and TFS-4 preferentially bound to small cell carcinoma cells and neuroblastoma cells, but not to non-small cell carcinomas (adenocarcinoma, squamous cell, or large cell). Especially, TFS-4 did not bind to a variety of other normal or malignant cells. Immunoprecipitation of the antigens by monoclonal antibodies and sodium dodecyl sulfate:polyacrylamide gel electrophoresis revealed that they had different molecular weights.
The smooth endoplasmic reticulum in hepatocytes of early postnatal and adult ddY male mice injected with phenobarbital was analyzed stereologically. The animals received daily intraperitoneal injections of phenobarbital and were killed about 24 h after the last injection. In early postnatal animals (injected with 35 mg/kg of the drug at days 1 and 2 after birth, or injected with 35 mg/kg at day 2 and with 50 mg/kg at days 3 and 4 after birth), the smooth endoplasmic reticulum proliferated both in perivenular and periportal hepatocytes; there was no significant difference in amount of smooth endoplasmic reticulum between the cells of the two zones. In adult animals, however, proliferation occurred only in perivenular cells after the administration of 35 mg/kg of phenobarbital for 2 days, and predominantly in perivenular cells even after the administration of 150 mg/kg of the drug for 7 days. These results suggest that the conspicuous proliferation of the smooth endoplasmic reticulum in perivenular hepatocytes in response to phenobarbital administration, which is characteristic of adult liver, does not occur in early postnatal mice but becomes manifest during postnatal development.
Male Wistar rats that had received a low dose of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) and sodium taurocholate showed a significantly higher incidence of hyperplastic and neoplastic lesions in the stomach mucosa than did the MNNG-treated controls. The result suggested an enhancing effect of taurocholate in stomach tumorigenesis.
The volume and shape (the axial ratio:length/diameter) of mitochondria in periportal and perihepatic hepatocytes from newborn, 5 days old, 10 days old and adult male ddY mice were analysed by quantitative electron microscopy. In newborn animals, the volume and relative histogram of the axial ratio were not significantly different between periportal and perihepatic cells. Thereafter, the volume did not change significantly in periportal cells, whereas it decreased between 5 days of age and the adult in perihepatic cells. In adult animals, the volume in perihepatic cells was 26% of that in periportal cells. The relative histogram of the axial ratio for periportal cells deviated significantly to smaller values than in that for perihepatic cells in 5 days old, 10 days old and adult animals. Thus, the structural heterogeneity of hepatocyte mitochondria, evident in adult animals, is not present in newborn animals but arises during postnatal development.
Forty-three children and 4 adults with Campylobacter enteritis were studied in the treatment of fosfomycin (FOM). FOM was administered per orally in doses ranging from 50 to 100 mg/kg/day for children and 3 g/day for adults for 5 days. Main symptoms such as diarrhea and fever were disappeared within 2 days on the average. Campylobacter jejuni in stool specimen disappeared within a week in 95% of these patients. The duration of main symptoms and the period of positive stool culture were evidently shortened in FOM-treated group compared with non-treated group. All of the isolated strains were sensitive to FOM by mono-concentration disk method. MIC50 of these strains remained between 1.56 and 3.13 micrograms/ml. None of these MIC was beyond 12.5 micrograms/ml.
No study has been reported of the effects of Goshajinkigan on male infertility. Thirty infertile male patients were orally given Goshajinkigan at a daily dose of 5.0 g for three months or more. Sixteen of these patients showed significant improvement in sperm motility. Ten cases showed effective increase in sperm count. Only one patients became pregnant during the period of administration of this drug. Laboratory examination showed no significant change in serum LH, serum FSH or prostaglandin E in seminal fluid. These results suggest that administration of TSUMURA-Goshajinkigan is effective as therapy for male infertility, but how this drug may be involved in promoting fertility should be investigated in future.
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The carcinogenic or cocarcinogenic effects of bile or bile acid on stomach carcinogenesis were investigated in inbred W rats. Bile or bile acid was introduced into the stomach by choledochogastrostomy or with food after the administration of N-methyl-N'-nitro-N-nitrosoguanidine [(MNNG) CAS: 70-25-7; 1-methyl-3-nitro-1-nitrosoguanidine] in drinking water. The animals that received MNNG and bile or sodium taurocholate (CAS: 145-42-6; N-choloyltaurine sodium salt) had a significantly higher incidence of hyperplastic and neoplastic lesions in the stomach mucosa than did the relevant MNNG-treated controls. The result suggested an enhancing effect of bile and sodium taurocholate in stomach tumorigenesis.
Three cases of renal angiomyolipoma are reported. The first case was a 53-year-old female with the complaint of left flank pain. In both cases selective angiography revealed a renal tumor, and computerized tomography disclosed a renal mass with low density corresponding to the fat tissue. From several examinations these two cases were preoperatively diagnosed as renal angiomyolipoma and nephrectomy was performed. Histopathological diagnosis was renal angiomyolipoma. The third case was a 64-year-old female with the complaints of left flank pain and macrohematuria. In this case computerized tomography revealed a renal mass which did not have a low density area. The possibility of renal cell carcinoma was considered and nephrectomy was performed. Histological diagnosis was renal angiomyolipoma which was primarily composed of smooth muscle cells. The first case had a calcified lesion in the brain. But there was no evidence of tuberous sclerosis in the following two cases. Some problems in diagnosis and treatment of renal angiomyolipoma are presented, and a statistical study is made on 194 reported cases of renal angiomyolipoma in Japan.
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Glucose 6-phosphatase activity is higher in the principal cell than in other cell types in the terminal segment and caudal half of the middle segment of the mouse epididymis. Effect of castration and testosterone replacement on the high enzyme activity in the principal cell was studied in the terminal segment and the caudal half of the middle segment (cytochemical study), and in the whole epididymis (biochemical study). Ten, 20, or 30 days after castration, the abundant amount of reaction product seen in principal cells from intact control animals decreased to the level in basal cells, halo cells, and smooth muscle cells. However, in animals treated with testosterone following castration, the reaction product in principal cells remained abundant. Changes in the biochemical activity after castration or testosterone administration following castration paralleled the cytochemical results. Thus, the high activity in the principal cell is under the control of testosterone.
Distribution of alkaline phosphatase (ALPase) activity on the plasma membrane of rat hepatocytes in primary monolayer culture was observed using the backscattered electron image (BEI) mode. Apparent reaction product was seen in hepatocytes cultured for 48 or 72 hours in a concentration of 8 X 10(5) cells per ml, and those cultured for 72 or 96 hours in a concentration of 6 or 4 X 10(5) cells per ml. The reaction product was observed as scattered fine dots, as spots, and as bands along the cell edge, with high contrast in flattened polyhedral hepatocytes forming cell trabeculae. The deposition of the reaction product was generally more abundant at the periphery of the cell trabeculae. X-ray microanalysis revealed that the reaction product contains both lead and phosphorus as real ALPase reaction product. In transmission electron microscopy, the reaction product was exclusively localized on the external surface of the plasma membrane. However, the plasma membrane adjoining the culture substratum was devoid of the reaction product. Further, the highest biochemical ALPase activity appeared in earlier culture stages when the density of cultured cells was larger. Thus, during a few days of culture, ALPase activity increases on the plasma membrane predominantly at the periphery of the hepatocyte trabeculae. This increase in the activity might be related to the mechanism of preserving the cell shape.
Ultrastructural localization of glucose-6-phosphatase activity was studied in the cells of the pancreas and submandibular gland of the mouse using a incubation medium modified from that of Wachstein & Meisel (1956). In pancreatic acinar cells, the reaction product for the enzyme activity was not found even after 90 min of incubation with three changes of the medium. However, the reaction product was localized in the endoplasmic reticulum and nuclear envelope of all other cell types composing the pancreas and submandibular gland. The reaction product appeared in moderate to abundant amounts in acinar cells and striated duct cells of the submandibular gland, and in the B cells, A and D cells of the pancreatic islet, but it was scarce in other cell types.