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Biomedical subjects

K Chida

Publications and source records attributed to K Chida.

267 records · Page 15Linked to original sources
PubMed1985

Inhibition of tumor promotion in mouse skin by 1 alpha,25-dihydroxyvitamin D3.

1 alpha,25-Dihydroxyvitamin D3 [1 alpha,25(OH)2D3], a hormonally active form of vitamin D3, was found to inhibit the promotional phase of 7,12-dimethylbenz[a]anthracene-induced skin carcinogenesis in female Sencar mice. Topical application of 1 alpha,25-(OH)2D3 once a week at a dose of 1 micrograms or less, a tolerable dose from hypercalcemia, dose dependently inhibited tumor promotion by 12-O-tetradecanoylphorbol-13-acetate (TPA). When 1 micrograms of 1 alpha,25(OH)2D3 was applied 30 min before 5 micrograms of TPA, the times required for 50 and 100% tumor incidence were delayed about 2.5 and 7 weeks, respectively, and the number of tumors per mouse was decreased by 25-30%. This inhibitory effect was more pronounced when examined by a two-stage promotion protocol, in which a single application of 5 micrograms of TPA (Stage I) was followed by repeated applications of 5 micrograms of mezerein once a week for 19 weeks (Stage II). When 1 alpha,25(OH)2D3 at 1 micrograms was applied at Stage I + II or Stage II, tumor formation was markedly suppressed, resulting in decrease of about 70-80% in the incidence and 87-90% in the number of tumors per mouse. Application of 1 alpha,25(OH)2D3 at Stage I only did not inhibit tumor formation, indicating that 1 alpha,25(OH)2D3 specifically inhibited Stage II promotion. These results are in good agreement with the previous and present findings that 1 alpha,25(OH)2D3 inhibited induction of epidermal ornithine decarboxylase by TPA and mezerein. The possibility that 1 alpha,25(OH)2D3 suppressed tumor promotion by killing initiated cells rather than inhibiting promotion was ruled out by an experiment in which TPA was applied to the 1 alpha,25(OH)2D3 alone-treated animals.

Animals↗
PubMed1984

Inhibition by 1 alpha, 25-dihydroxyvitamin D3 of induction of epidermal ornithine decarboxylase caused by 12-O-tetradecanoylphorbol-13-acetate and teleocidin B.

Topical application of 1 alpha, 25-dihydroxyvitamin D3 [1 alpha, 25-(OH)2D3], an active form of vitamin D3, markedly inhibited induction of ornithine decarboxylase caused by 12-O-tetradecanoylphorbol-13-acetate (TPA) and teleocidin B in mouse skin. The degree of inhibition was dependent on the dose and time of application of 1 alpha, 25(OH)2D3. Application of 1 micrograms 1 alpha, 25(OH)2D3 within 30 min before or after treatment with 10 micrograms TPA caused about 72% inhibition of ODC induction at 4 hr. Similar degrees of inhibition were obtained with dose ratios of 1 alpha, 25(OH)2D3 to TPA of 1:3, 1:10, and 1:30. The dose required for 50% inhibition was 0.063 micrograms, or 0.15 nmol, which is about one-half that of retinoic acid, a known inhibitor of induction of ODC activity by TPA. 1 alpha, 25(OH)2D3 had a specific inhibitory effect, in which 100 times higher doses or more of other derivatives of vitamin D3, such as 1 alpha-hydroxyvitamin D3, 25-hydroxyvitamin D3, 24R,25-dihydroxyvitamin D3, and vitamin D3, were required to inhibit ODC induction by TPA. 1 alpha, 25(OH)2D3 did not inhibit epidermal hyperplasia induced by TPA.

Alkaloids↗
PubMed1984

Inhibition of DNA synthesis and sugar uptake and lack of induction of ornithine decarboxylase in human epidermal cells treated with mouse skin tumor promoters.

The present study was undertaken to investigate the possibility that 12-O-tetradecanoylphorbol-13-acetate (TPA) is active as a tumor promoter in human skin. Human epidermal and dermal cells were isolated from the skin of normal subjects by trypsinization and separation of the epidermis from the dermis. Cells in primary culture were exposed to a wide range of TPA concentrations (0.001 to 1000 ng/ml) for various time intervals, and its effect on DNA synthesis, sugar uptake, and polyamine synthesis was measured. Results obtained using human cells were compared with those for the corresponding cells isolated from Sencar mice. In human epidermal cells, TPA did not stimulate but instead inhibited DNA synthesis and uptake of 2-deoxy-D-glucose (DG), a glucose analogue. Inhibition of DNA synthesis could be detected at a dose of TPA as low as 0.1 ng/ml, while at 10 ng/ml DNA synthesis was 50 to 70% of the control. Inhibition of DG uptake depended on concentration of and length of exposure to TPA. Exposure to TPA (10 ng/ml) for 3 hr resulted in a 35% inhibition of DG uptake. Furthermore, exposure of human epidermal cells to TPA under various conditions, including the use of uncultured, freshly isolated cells and of a low-calcium medium, did not result in induction of ornithine decarboxylase, a key enzyme in the synthesis of polyamine. Teleocidin B, a tumor promoter, structurally unrelated to TPA but with an ornithine decarboxylase inducibility in mouse skin similar to that of TPA, also failed to induce ornithine decarboxylase activity in human epidermal cells. Mouse epidermal cells reacted differently from human epidermal cells on addition of TPA. DNA synthesis, sugar uptake, and polyamine synthesis were all stimulated. DG uptake alone was stimulated in human and mouse dermal cells treated with TPA.

Animals↗
PubMed1983

Participation of the nucleus locus coeruleus in DOCA-salt hypertensive rats.

The locus coeruleus was subjected to biphasic electrical stimulation, and a group of deoxycorticosterone acetate (DOCA)-salt hypertensive rats revealed a greater pressor response than a group of normotensive control rats. The pressor threshold current (i.e. minimum current to raise the arterial pressure by 10 mm Hg) of DOCA-salt hypertensive rats was also lower. The threshold current was low even in the prehypertensive stage of DOCA-salt treated rats. During arterial pressure fall, the pressor threshold current lowered only in normotensive rats and neither group underwent a change during pressure rise. These data indicated that the locus coeruleus had a pressor role and it had been accelerated in DOCA-salt treated rats before hypertension was evident. Following bilateral electrical lesions of the locus coeruleus no significant differences were observed in the arterial pressure changes, while vascular reactivity to norepinephrine did not differ between the two groups. The results suggest that the locus coeruleus may be involved in the development of hypertension but may not be important in the maintenance of it.

Animals↗
PubMed1983

1 alpha,25-Dihydroxyvitamin D3 markedly enhances chemically-induced transformation in BALB 3T3 cells.

1 alpha,25-Dihydroxyvitamin D3, a hormonally active form of vitamin D3, enhanced methylcholanthrene-induced transformation in BALB 3T3 cells to a much greater extent than 12-O-tetradecanoylphorbol-13-acetate. This enhancement was probably mediated by a cytosol receptor for 1 alpha,25-dihydroxyvitamin D3 which has an equilibrium constant of 28.4pM and a maximum binding of 32.6 fmol/mg protein.

Animals↗
PubMed1983

Presence of specific binding sites for phorbol ester tumor promoters in human epidermal and dermal cells in culture but lack of down regulation in epidermal cells.

The presence of specific binding sites for phorbol esters was demonstrated in human epidermal and dermal cells in culture by assay of binding of [3H]phorbol-12,13-dibutyrate (PDBU) to intact cells. The specificity of the binding was shown by displacement of the binding with biologically active tumor promoters, such as 12-O-tetradecanoylphorbol-13-acetate, teleocidin B, and mezerein, but not with inactive derivatives. The equilibrium binding data were analyzed by the Scatchard method and fitted by a straight line to the model of a single class of binding sites. Human epidermal cells bound PDBU with a Kd of 28 nm at 3.7 X 10(6) molecules per cell, while human dermal cells bound PDBU with a Kd of 27 nm at 2.1 X 10(6) molecules per cell. These values were compared with those of epidermal and dermal cells of mice. Although mouse cells showed the same affinity as did human cells, mouse epidermal cells bound one-third as much as human epidermal cells, and mouse dermal cells bound one-fifth as much as human dermal cells. When precultured with unlabeled PDBU for 24 hr, [3H]PDBU binding decreased time dependently in all cells except human epidermal cells. Thus, the binding of phorbol esters to human epidermal cells is unique in that there are a large number of binding sites compared with mouse epidermal cells, and there is no down regulation.

Binding Sites↗
PubMedDate not supplied

Sympathetic dysfunction mediating cardiovascular regulation in alcoholic neuropathy.

We evaluated autonomic function in alcoholic neuropathy by non-invasive hemodynamic studies using servo-plethysmo-manometry and laser Doppler flowmetry. In 16 alcoholics compared with 17 age-matched healthy controls, the extent of AP responses to phase IV of the Valsalva maneuver, cold pressor test and isometric exercise decreased significantly, indicating sympathetic hypofunction. Five patients had paradoxical depressor response to cold pressor test, which was reproducible by submersion of the hand in warm water. The data suggest involvement of the higher autonomic center. Reflex bradycardia in phase IV of the Valsalva maneuver and the variation coefficient of R-R intervals in the electrocardiogram were lower, indicating parasympathetic hypofunction. Cutaneous blood flow response in the foot upon local warming and submersion of the hand in cold water was significantly impaired, but that in the contralateral hand was not. Abnormalities in the autonomic function tests may result from a toxic effect of ethanol on the peripheral and central autonomic nervous system and the cardiovascular system. The results indicate not only parasympathetic (vagal) but sympathetic dysfunction mediating cardiovascular regulation in patients with alcoholic neuropathy.

Adult↗