Biomedical subjects
Publications and source records attributed to J Kato.
The specific binding of R5020 to the 7S cortical progestin receptors was markedly inhibited by unsaturated long chain fatty acids, such as oleic acid, arachidonic acid, and docosahexaenoic acid. The inhibitory effect of docosahexaenoic acid was dose-dependent in the range of 1.5 X 10(-6) M to 1.5 X 10(-4) M.
The externalization of transferrin receptors was found in established human tumor cell lines at the rate of 10-35 ng/hour/10(6) cells, when they were incubated with transferrin at 37 degrees C. This externalization is inhibited by lowering the incubation temperature to 4 degrees C or eliminating the ligand from the culture medium. Metabolic inhibitors such as sodium azide, colchicine, cytochalasin B and chloroquine also decreased the rate of externalization. Almost 95% of released transferrin receptors were precipitated by centrifugation at 100,000 x g for 30 min, suggesting that transferrin receptor is externalized into the medium as a vesicular form.
Among components alpha, beta, and gamma of penicillin-binding protein 1b, the alpha and gamma components were confirmed to represent the primary gene products by agreement of their N-terminal amino acid sequences with those predicted from the nucleotide sequence of the ponB (penicillin-binding protein 1b) gene with exclusion of the first methionine in each component. The generation of beta occurred primarily after cell disruption, and the simultaneous loss of alpha suggested the conversion of alpha to beta. The N-terminal amino acid sequence analyzed for beta showed that the conversion was due to the removal of 24 amino acids from the N terminus of alpha.
Although synthetic atrial natriuretic peptide is known to increase urinary volume and sodium excretion and to reduce arterial blood pressure, the physiological role of endogenous atrial natriuretic peptide is still unclear. We investigated the effects of specific rabbit antiserum against alpha-rat atrial natriuretic peptide on hemodynamics, diuresis, and natriuresis in anesthetized rats. A significant rise in mean blood pressure lasted for about 60 minutes after intravenous administration of the antiserum, with the maximal increment being approximately 7%. Similarly, a significant increase in cardiac output was obtained 20 minutes after injection at an increment of approximately 11%. Heart rate, however, remained unchanged. On the other hand, significant reductions in urine output and urinary sodium and potassium excretion lasted for about 20 minutes after administration of the antiserum, with maximal decrements being 63%, 63%, and 60%, respectively. No significant effects on hemodynamics, diuresis, and natriuresis were observed following injection of normal rabbit serum. These results indicate that endogenous atrial natriuretic peptide has an important physiological role in the regulation of hemodynamics and water-electrolyte balance.
The clinical significance of radioreceptor assay for transferrin receptors of human cancerous tissues was evaluated. Fresh surgical specimens from various carcinoma tissues were solubilized with 1% Triton X-100 and the extracts were mixed with 125I-labelled diferric transferrin. The free transferrin and the receptor-bound transferrin were separated by 15% polyethylene glycol precipitation. The % specific transferrin binding to gastric, colonic, lung and mammary carcinoma tissues ranged between 3.9 and 13.9%, whereas those for normal stomach and colon were less than 2%. The concentrations of transferrin receptors in these cancerous tissues ranged between 3.7 and 28.3 pmole/g tissues. It was concluded that the amounts of transferrin receptors were significantly increased in all of the tumor tissue extracts examined and may thereby provide a useful marker for the diagnosis of malignancies.
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The major structural difference between p60c-src and p60v-src resides in the carboxy-terminal region. We introduced substitution, replacement and deletion into the carboxy-terminal region of chicken p60c-src and examined the effects on its biochemical and biological properties in chicken embryo fibroblasts. The replacement of the carboxy-terminal region after amino acid position 515 of p60c-src with the corresponding region of p60v-src converted p60c-src to a transforming protein with elevated kinase activity. The substitution of Tyr527, which is a major tyrosine phosphorylation site of p60c-src, with phenylalanine resulted in an increase of kinase activity and in transforming ability. On the other hand, a deletion after position 515 abolished the kinase activity. These results revealed the structural features of the carboxy terminus of p60c-src that are required for the regulation of its intrinsic protein kinase activity.
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A case of perforated early gastric cancer and a collective review of the relevant Japanese literature is reported. A 83-year-old woman with free air discovered by an abdominal X-ray, was referred to our hospital. On operating, a perforated ulcer was found within and lesions, indicative of a IIc + III type early gastric cancer. Macroscopically, there was an elevated lesion at the antrum of the stomach as well. Histologically, these lesions were connected and moderately differentiated adenocarcinoma. Another lesion was also found at the anterior wall and diagnosed as IIb type gastric cancer.
Tamoxifen is a nonsteroidal antiestrogen whose mode of action is, as yet, unclear. The purpose of this report is to investigate the effects of Tamoxifen on endometrial adenocarcinoma ultrastructurally. Five patients with endometrial adenocarcinoma, 3 cases well differentiated and the others undifferentiated, were treated with 20mg Tamoxifen per os a day for 7 days, and the following changes were observed: The cells became roundish and slightly swollen. Development of cytoplasmic organelles was observed. In the cytoplasm, glycogen granules did not increase. These results suggest that an anti-cancer effect is brought about by the induction of the tissue toward functional differentiation as well as inhibition of glycogen metabolism in tumor cells.
The results of treatment of 40 cases of primary malignant tumor of the small intestine are reported. The malignant tumors included 14 leiomyosarcoma, 12 malignant lymphoma and 14 adenocarcinoma. Our standard treatment for these tumors was segmental resection of the small intestine with its mesentery including the regional lymph nodes and we used additional adjuvant chemotherapy for some cases of malignant lymphoma and adenocarcinoma. Curative resection was performed in 57.1% of leiomyosarcoma, 50.0% of malignant lymphoma and 61.5% of adenocarcinoma. Cumulative 5-year survival rates were leiomyosarcoma 21.4%, malignant lymphoma 53.0% and adenocarcinoma 43.3% respectively. Serosal infiltration, lymph node metastasis and operative curability proved to be the prognostic factors. In particular, the 5-year survival rate of patients on whom curative resection could be performed was significantly better for each tumor type than that of patients for whom this was not possible, the figures being leiomyosarcoma 40.0%, malignant lymphoma 83.3% and adenocarcinoma 83.3%.
Serum transferrin receptors were measured by a sandwich radioimmunoassay procedure in patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia. The mean circulating transferrin receptor concentration of normal subjects and patients with iron deficiency anemia, autoimmune hemolytic anemia and aplastic anemia are 253 +/- 82 ng/mL, 730 +/- 391 ng/mL, 1,426 +/- 1,079 ng/mL, and 182 +/- 39 ng/mL, respectively. The values for those with iron deficiency anemia and autoimmune hemolytic anemia were significantly higher than that of normal controls and the values for those with aplastic anemia were lower than that of normal controls. After iron supplementation in iron deficiency anemia, the serum transferrin receptor values increased twofold over those of pretreatment values. This increase parallels an increase in peripheral reticulocytes. Therefore, the number of circulating transferrin receptors in anemic patients may reflect the level of bone marrow erythropoiesis and is a potentially useful new index for red cell production.
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To investigate the time course effect of sodium intake on release and synthesis of atrial natriuretic polypeptide (ANP), plasma and atrial content of ANP were measured in rats which had been fed either a high or a low salt diet for 1, 3, 7, 14 and 35 days. Plasma ANP in rats fed the high salt diet for one day was significantly higher than in those fed the low salt diet. However, there were no significant differences between the groups fed either the high or the low salt diet for 3 days or more. In contrast to the direction of change in plasma ANP, atrial content of ANP in rats fed the high salt diet for one day tended to be lower and was significantly lower in those fed for 3 and 7 days than in the low salt diet group, while there were no significant differences between both groups that were fed for 14 and 35 days. These results suggest that ANP is rapidly released into the circulation when sodium is loaded, however, the atrial storage of ANP remains depleted for about one week.
To investigate the releasing mechanisms of atrial natriuretic polypeptide (ANP), identical amounts of 5% glucose solution, isotonic (0.9%) or hypertonic (5%) saline were infused intravenously for 5 min (2 ml/min) in anesthetized rats. At the same time, plasma immunoreactive ANP (ir-ANP) was measured using a direct radioimmunoassay. Plasma ir-ANP increased after infusion of 5% glucose solution (P less than 0.01) and isotonic saline (P less than 0.05), and returned rapidly to the basal levels in the recovery period. Plasma ir-ANP increased to a greater degree in the group infused with hypertonic saline than in the other two groups. The major immunoreactive component of increased ir-ANP was identified as alpha-rat ANP, a 28 amino acid residue, by using reverse phase high-performance liquid chromatography. These results suggest that sodium ions may be a stimulating factor of ANP release as well as volume expansion.
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