[Polyneuropathy: familial dysautonomia].
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Biomedical subjects
Publications and source records attributed to M Kurata.
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Effects of organochlorine pesticides on the metabolic cooperation in the hypoxanthine-guanine-phosphoribosyl-transferase system using wild-type 6-thioguanine-sensitive V79 cells and variant 6-thioguanine-resistant cells were surveyed. The metabolic cooperation was inhibited by 1,1,1-trichloro-2,2-bis(p-chlorophenyl)ethane (DDT), 1,1-dichloro-2,2-bis(p-chlorophenyl)ethane (TDE), 1,1,1-trichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDT), 1,1,1-trichloro-2,2-bis(p-methoxyphenyl)ethane (methoxychlor), aldrin, dieldrin, endrin, heptachlor, alpha-isomer of benzene hexachloride (alpha-BHC), and gamma-BHC, but not beta-BHC. The present results suggest that the pesticides which inhibited the metabolic cooperation may be tumor promoters.
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Twenty patients with primary breast cancer were treated with tamoxifen (10 mg p.o. twice a day) for 1 to 4 weeks. Before and after the tamoxifen administration, tumor specimens were obtained and assayed for estrogen receptors and progesterone receptors (PGR). Total cytosol estrogen receptor (ERC) and occupied nuclear estrogen receptor (ERN) were measured by hydroxylapatite assay, and unoccupied PGR was measured by the dextran-coated charcoal assay. ERC, ERN, and PGR were detectable in 11, 8, and 6 tumors, respectively, before tamoxifen administration. After tamoxifen treatment, ERC decreased in 10 of 11 ERC-positive tumors. Occupied ERN increased in three of five ERN-positive tumors treated with tamoxifen for a short period (1 to 2 weeks), but they decreased in all of three ERN-positive tumors after longer administration (3 to 4 weeks). PGR increased in three of five ERN-positive tumors after short-term tamoxifen treatment, but they decreased in all of three tumors treated by the drug for a longer period. Increased PGR responses were accompanied by an increase of ERN in two of three ERN-positive tumors. These results suggest that tamoxifen interacts with the estrogen receptor system in human breast cancer tissue and may be estrogenic during short treatment, while longer treatment results in an antiestrogenic response.
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The interaction between [131I]-thyroglobulin liposomes and thyroidal lysosomes was used as an in vitro model system for analyzing the relation of colloid droplets to lysosomes in follicular cells. The rates of hydrolysis of [131I]-thyroglobulin in a liposome-lysosome system (Lipo-Lyso system) and a thyroglobulin-lysosome system (TG-Lyso system) were compared. Hydrolysis of thyroglobulin in the Lipo-Lyso system increased hyperbolically and was greater than that in the TG-Lyso system for about 10 h. Liposomal thyroglobulin was not degraded by the 20,000 X g supernatant obtained on disruption of the lysosomal fraction. On varying the pH of the incubation medium, the highest activity was observed under acidic conditions in both systems. Under neutral or weakly alkaline conditions, the Lipo-Lyso system still showed 50% of the maximal hydrolytic activity, while the TG-Lyso system showed no activity. ATP and anaerobic conditions had no effect on either system. Cysteine (5 X 10-2M) and p-chloromercuribenzene sulfonic acid (PCMBS, 10-3 M) had not influence on hydrolysis in the Lipo-Lyso system, but in the TG-Lyso system cysteine greatly increased, and PCMBS significantly reduced the rate of hydrolysis. Dibutyryl cyclic AMP had no effect. Chlorpromazine (Cpz) decreased liposomal thyroglobulin hydrolysis in a concentration-dependent manner. In the TG-Lyso system, concentrations of 10-4M Cpz had no effect. These results strongly suggest that liposomes rapidly fused with lysosomes, providing optimal conditions for hydrolysis of thyroglobulin.
The concentration of IgE in the serum of Sprague-Dawley rats increased after infection with Nippostrongylus brasiliensis (NB). The IgE concentration in normal rats was less than 1 mug/ml. After re-infection with NB, the concentration increased in 100 to 300 mug/ml. Mast cells were purified from peritoneal cells of both normal and NB-infected animals. Purified mast cells from the infected animals released histamine upon exposure to NB antigen. The antibody specific for IgE released histamine from purified mast cells of both normal and infected animals. Dose-reponse curves of histamine release suggested that mast cells from NB-infected animals bear more IgE molecules than normal mast cells. Binding of 125I-labeled rat E myeloma protein with normal mast cells was demonstrated by autoradiography. Under the same experimental conditions, mast cells of infected animals were not labeled with 125I-IgE. Mast cells from both normal and infected animals failed to combine 125I-labeled IgG. The number of IgE molecules bound per mast cell was determined by incubating 125I-labeled IgE with purified mast cells. When mast cells were incubated incubated in 0.6 to 2 mug/ml of IgE, the number of IgE molecules combined with the mast cells from infected animals was about 10% of that bound with normal mast cells. The results indicated that a large proportion of IgE receptors on mast cells of infected animals was occupied by their own IgE. No significant difference was observed between normal mast cells and those of infected animals with respect to histamine content and intracellular levels of cyclic nucleotides.
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