Gravitational effects on mammalian cells.
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Biomedical subjects
Publications and source records attributed to Y Kumei.
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With the aim of studying the mechanism by which peripherally injected interleukin-1 increases the serum levels of insulin in conscious rats, the effects of indomethacin, a cyclooxygenase inhibitor, on interleukin-1-induced hyperinsulinemia were examined using male Wistar rats implanted with intra-atrial cannulas. The i.v. injection of interleukin-1 (1 microgram/rat) into conscious rats resulted in a significant increase in serum insulin levels with the peak response being observed 10 min after injection. It was also found that this insulin response to interleukin-1 was dose-related. Pretreatment with indomethacin (3 mg/kg body weight), however, completely blocked the interleukin-1-induced stimulation of insulin secretion. These findings suggest that i.v. injected interleukin-1 stimulates insulin release from the endocrine pancreas by a mechanism involving the prostaglandin system.
We have shown that hypergravity (35g) stimulates production of inositol 1,4,5-trisphosphate (IP3) and decreases adenosine 3',5'-cyclic monophosphate (cAMP) levels in HeLa cells. IP3 production rapidly increased 1.5- and 2.1-fold greater (P less than 0.05) than the control after 2- and 5-min exposures to 35g, respectively. The intracellular cAMP levels, determined in the presence of isobutylmethylxanthine, were decreased by 11% (P less than 0.05) and 16% (P less than 0.01) relative to the control after 10- and 20-min exposures to 35g, respectively. The phosphorylation of proteins which were immunoprecipitated by antibodies recognizing microtubule-associated proteins (ipMAPs) was also apparent after exposure of these cells to hypergravity. In the detergent-insoluble fraction, phosphorylation of a 115-kDa protein was significantly enhanced compared to the control after a 5-min exposure to 35g. In the detergent-soluble fraction, phosphorylation of a 200-kDa protein was observed served after a 20-min exposure to 35g. Our study suggests that IP3 and cAMP may act as second messengers in hypergravity signal transduction. Phosphorylation of ipMAPs in both the detergent-soluble and -insoluble fractions suggests that cytoskeletal structures may be influenced by gravity.
We have found that hypergravity stimulates the proliferation of HeLa cells through reduction of the G1 phase duration, concomitant with enhancement of c-myc gene expression. HeLa cells were grown in monolayer in culture flasks that were centrifuged to generate a constant 18, 35 or 70 g at 37 degrees C for up to 4 days. The cell proliferation was enhanced at 18, 35 and 70 g, most notably at 35 g. Cell cycle analyses with [3H]thymidine (TdR)-colcemid treatment showed that the cell generation time in the 35 g culture was reduced by 17% as compared to the control, which was attributed to a 26% reduction of the G1 phase duration. No differences were observed in the duration of the S, G2 and M phases or in the [3H]TdR incorporation per S phase cell between the 35 g culture and the control. The induction of c-myc gene expression was investigated by RNA blot hybridization during a 15-360 min exposure of cells to 18, 35 and 70 g. Elevated levels of c-myc mRNA were observed after a 15-min exposure, and maintained after a 360-min exposure at all hypergravities examined. The highest induction rate of c-myc mRNA was 3.8-fold higher than the control after a 120-min exposure to 35 g. The 35 g condition was the most effective hypergravity for stimulating both cell proliferation and c-myc gene expression. Our study suggests that the appropriate level of hypergravity stimulates HeLa cell proliferation by reducing the G1 phase duration without affecting DNA synthesis rate, mediated through induction of c-myc gene expression.
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A 39 year-old-man and a 44 year-old-woman who was his elder sister were admitted to our hospital for study and treatment of goiter and hypothyroidism. Both had giant goiters. When he was about 3 years old goiter was first noticed since then the goiter slowly increased in size until the time of admission, while her goiter increased in size from when she was about 30 years old. Though both cases were already recognized as cretinism, they had not been treated. Perchlorate discharge test showed impaired iodide organification in both cases. Their serum thyroglobulin concentration was extremely high (1800 ng/ml). To our knowledge, there have been no case reports of goiterous cretinism due to impaired iodide organification with hyperthyroglobulinemia except the report by Hirota, Y. et al.
Serum amylase isozyme was determined in 2 cases with normal urinary amylase but persistantly high serum amylase. Both cases showed dominant S-type amylase associated with tailing findings that was characteristic of macroamylasemia. Moreover, using the immunofixation method, the serum amylase was found to be bound with IgG (K) in case 1 and with IgA (L) in case 2.
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An investigation was made to determine the effects of the addition of selenium to the silver-tin amalgam alloy. The addition of 0.2 wt% to 0.6 wt% selenium in the alloy completely eliminated the cytotoxicity, evaluated by the 51Cr release assay and morphology, of the silver amalgam on the L cells and JTC-12 cells. The physical properties of the amalgam containing 0.2 wt% selenium in the alloy were tested according to the American Dental Association Specification No. 1 for Alloy for Dental Amalgam and were found to meet the requirements.
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