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Biomedical subjects

M Fukuda

Publications and source records attributed to M Fukuda.

At least 1,207 records · Page 67Linked to original sources

Positive and negative regulation of specific gene expression by the tumor promoter TPA in human erythroleukemic K562 cells.

The potent tumor promoter 12-O-tetradecanyl-phorbol-13-acetate (TPA) has been shown to have profound effects on many mammalian cell types grown in tissue culture. In the human erythroleukemic cell line K562, TPA causes inhibition of cell growth, attachment to plastic dishes and a flat, irregular cell morphology. Accompanying these changes is a reduction in the expression of two cell surface glycoproteins, Gp-105 and glycophorin, which are specific to intermediate and late stages of erythroid cell development (Fukuda 1981). In this study, we found that TPA treatment leads to a reduction in the incorporation of [35S]-methionine into glycophorin which suggests that regulation occurs at the level of de novo biosynthesis. We also examined the effect of TPA on the biosynthesis of other cellular proteins. We found that TPA treatment leads to a de novo induction of two cytoskeletal proteins, vimentin and actin. To further examine the mechanism of action of TPA, we isolated RNA from K562 cells, translated it in vitro, and examined the products by immunoprecipitation. TPA was found to rapidly reduce the level of glycophorin mRNA activity; a 5-fold reduction was noted as early as 1 hour after TPA treatment. Concurrently, the level of vimentin mRNA activity increased. By hybridization of a human actin cDNA probe to K562 RNA, we also found that TPA treatment leads to a rapid induction of actin mRNA. These results suggest that some of the effects of TPA, including possibly tumor promotion, may be due to both positive and negative transcriptional regulation of specific genes.

Actins↗

Hormone-dependent changes of blood vessels in DMBA-induced rat mammary carcinoma and its regression studied by 3H-thymidine autoradiography.

Using DMBA-induced rat breast cancer, the changes in the histology and proliferative activity underlying the phenomenon of tumor regression by hormone therapy were studied by 3H-thymidine autoradiography. The control tumor was found to essentially consist of two histologically different areas, medullary (A area) and tubular or cystic (B area). The cancer cells in the A area were homogeneously proliferating with a cell cycle time of 51h, and among those in the B area, 65% were proliferating with a cell cycle time of 81h while 35% were non-proliferating. Among the various-kinds of hormone therapies, ovariectomy plus male sex hormone administration was most effective in inducing tumor regression. In the regressed tumor, the A area was greatly diminished due to central necrosis and replaced by cystic B area. In the remaining A area, the cell cycle time was lengthened to 97h, and that for the proliferating cells in the B area was as long as 118h. The most striking histological change after ovariectomy plus male sex hormone administration was the diffuse necrosis of the capillary endothelial cell within 24h, followed by hemorrhage, central necrosis in the A area (1W), and final stage of fibrosis (2W). The tumor administered with female sex hormone after ovariectomy showed a rebound growth from the regression, due to the initial reactivation of the endothelial cell proliferation and following stimulation of cancer cell mitotic activity. From these observations, it is concluded that the capillary endothelial cells in DMBA-induced rat breast cancer are estrogen dependent, and that the tumor regression induced by decreased estrogen-level is attributable to the massive necrosis from capillary insufficiency and anoxia.

9,10-Dimethyl-1,2-benzanthracene↗

[46, XX true hermaphroditism: a case report with a review of 37 cases reported in Japan].

The patient was a 17-year-old male who had undergone chordectomy at the age of 5 years. The patient visited us with the chief complaint of ectopic urethral opening and breast growth at the end of May, 1980. Urethrography revealed a well developed vagina and a unicordial uterine. The upper portion of bilateral gonads were cystic and nodular by palpation. Sex chromatin examination using buccal smear revealed X chromatin positive and Y chromatin negative. Chromosomal constitution was 46, XX karyotype and H-Y antigen was positive. Since the patient hoped to remain as male, he received gonadectomy, hysterectomy and implantation of thesis prosthesis into his scrotum. Histopathologically, bilateral gonads were ovotestes and neither vas nor fallopian tube was present. Postoperatively, he received supplement therapy with testosterone with successful results concerning his secondary sexual characters.

Adolescent↗

[A case of embryonal rhabdomyosarcoma of the kidney].

A case of embryonal rhabdomyosarcoma of the left kidney is reported. A 16-year-old boy was admitted with the complaint of left abdominal pain and fever on January 6, 1983. Radiological examination showed a tumor of the left kidney; and, nephrectomy was performed. Histopathologically the entire tumor was composed of undifferentiated round cells. Diagnosis of embryonal rhabdomyosarcoma was made on the basis of special stains including immunohistochemical study with nervous tissue specific enolase. Although radiation and chemotherapy were performed postoperatively, the tumor recurred and the patient died on October 22, 1983. The problems of differential diagnosis of embryonal rhabdomyosarcoma from sarcomatous types of nephroblastoma, particularly rhabdoid tumor and other undifferentiated renal tumors were discussed. Fifteen rhabdomyosarcoma of the kidney including our case have been reported in the Japanese literature.

Adolescent↗

Computer analysis of sub-parameters of depurination and depolymerization rate constants in Feulgen DNA hydrolysis.

Feulgen DNA hydrolysis curves derived from cytofluorometry at various temperatures and HCl concentrations were computer analyzed with least squares fit to Bateman function. By comparing the depurination (k1) and depolymerization (k2) rate constants at different hydrolysis conditions, it was found that the two parameters of temperature and HCl concentration can be expressed as k = AN2 X exp (-B/T), where A and B are constants, N is the HCl concentrations, and T is the absolute temperature. From the analysis of Feulgen hydrolysis curves with 2N HCl at various temperatures, it was calculated that A = 5.3590 X 10(14) and B = 12133.543, for k1, and A = 6.2401 X 10(14) and B = 12181.660, for k2 for mouse 4C hepatocytes fixed with absolute methanol. Computer generated theoretical hydrolysis curves using the above k1 and k2 values were compared with experimental curves at various temperatures and HCl-concentrations. The two types of hydrolysis curves coincided with each other when 1-3 N HCl was used at temperatures between 30-40 degrees C. The peak times of hydrolysis curves at different conditions determined by experimental analysis and theoretical estimations also coincided reasonably well with each other. The physico-chemical phenomena underlying the equation designating k1 and k2 values are discussed.

Animals↗

The effects of feeding and rewarding brain stimulation on lateral hypothalamic unit activity in freely moving rats.

In some medial forebrain bundle (MFB) sites, self-stimulation is often modulated by hunger or satiety. With electrodes in the nucleus accumbens (NAC) such modulation rarely occurs. The influence of food deprivation on MFB self-stimulation is the main basis for the hypothesis that electrical stimulation of the MFB can mimic the rewarding effect of food for hungry animals. To investigate this hypothesis, unit activity was recorded from the lateral hypothalamic area (LHA) of freely moving rats during rewarding stimulation at loci in both MFB and NAC, and during food ingestion. Of 63 neurons tested during MFB stimulation, 41 were inhibited, 19 were activated, and 3 were not influenced. NAC stimulation suppressed 8 of the 31 neurons tested, excited 16, and elicited no response in the remaining 7. During ingestion, 29 of the 63 neurons tested were inhibited and one was facilitated. Of 29 neurons suppressed by food, 20 were also inhibited by rewarding MFB stimulation, but 10 of 13 neurons inhibited by food were excited by rewarding NAC stimulation. Thus, most LHA neurons inhibited during feeding were also inhibited by rewarding MFB stimulation. Rewarding NAC stimulation, however, does not inhibit most LHA neurons that are inhibited by food. This result suggests that LHA neurons which are inhibited by food might be involved in mediation of the rewarding effect of electrical stimulation at some sites in the MFB. Nevertheless, self-stimulation may occur by activating reward processes other than those related to food, because rewarding NAC stimulation does not inhibit LHA neurons which are suppressed by food.

Action Potentials↗