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Biomedical subjects

T Suda

Publications and source records attributed to T Suda.

At least 919 records · Page 51Linked to original sources

Differentiation of mouse myeloid leukemia cells induced by 1 alpha,25-dihydroxyvitamin D3.

Mouse myeloid leukemia cells can be induced to differentiate into macrophages in vitro by 1 alpha,25-dihydroxyvitamin D3, the active form of vitamin D3. The minimal concentration of 1 alpha,25-dihydroxyvitamin D3 to induce the cell differentiation was 0.12 nM. The degree of cell differentiation in various markers induced by 12 nM 1 alpha,25-dihydroxyvitamin D3 was nearly equivalent to that induced by 1 microM dexamethasone, the most potent known stimulator. Among several markers of the differentiation by 1 alpha,25-dihydroxyvitamin D3, phagocytic activity was induced within 24 hr, and this was followed by induction of lysozyme and locomotive activities. Similar changes were also induced by 0.01-1 microM 1 alpha-hydroxyvitamin D3. 25-Hydroxyvitamin D3 and 24R,25-dihydroxyvitamin D3 showed only weak inducing activity. These results suggest the possibility that, in addition to its wellknown biological activities in enhancing intestinal calcium transport and bone mineral mobilization, 1 alpha, 25-dihydroxyvitamin D3 is involved in the differentiation of bone marrow cells.

Animals↗

Effect of hydrocortisone on long-term human marrow cultures.

In human long-term marrow cultures a relatively high concentration of hydrocortisone (10(-6) M or more) is necessary for the development and subsequent maintenance of some cellular components in the adherent cell layer. However, such concentrations of hydrocortisone seem to be inhibitory for the production of granulocyte/macrophage progenitor cells (GM-CFC). In further attempts to improve these cultures, therefore, it is important to maintain a balance between a concentration of hydrocortisone which is necessary for the development of a competent adherent layer and the concentration which is inhibitory to the production of GM-CFC.

Bone Marrow↗

Suppression of in vitro granulocyte-macrophage colony formation by the peripheral mononuclear phagocytic cells of patients with idiopathic aplastic anaemia.

To investigate whether phagocytic cells play a role in the pathogenesis of aplastic anaemia, we studied the effect of the mononuclear phagocytic cells in the peripheral blood from patients with idiopathic aplastic anaemia on granulocyte-macrophage colony (GM-colony) formation. There was no apparent infection in the studied patients. In nine out of 20 cases the mononuclear cells suppressed the formation of GM-colonies by normal bone marrow. Removal of the phagocytic cells by carbonyl iron powder caused a loss of this suppressive effect. These results suggest the requirement for phagocytic cells in this suppressive effect and the possible involvement of phagocyte-mediated immunological mechanism in the pathogenesis of some cases of idiopathic aplastic anaemia.

Adult↗

Plasma pituitary hormone responses to the synthetic enkephalin analog (FK 33-824) in normal subjects and patients with pituitary diseases.

D-Ala, Mephe, Met, enkephalin (Sandoz FK 33-824) is a stable long acting analog of methionine-enkephalin. FK 33-824 (0.5 or 1.0 mg), elicited plasma GH and PRL responses in normal subjects. In 23 patients with pituitary dwarfism, the response of plasma GH was markedly impaired, while PRL responded to a variable degree. In patients with acromegaly, there was little or no increase in GH and PRL after FK 33-824. Plasma GH increased to a variable degree after FK 33-824 in patients with hyperprolactinemia, with little change in plasma PRL. FK 33-824 decreased plasma cortisol in normal subjects and patients with pituitary disease. These results show that patients with acromegaly and hyperprolactinemia due to pituitary adenomas and patients with pituitary dwarfism do not respond well to FK 33-824, presumably because of hypothalamic or pituitary derangement.

Acromegaly↗

Failure to demonstrate the stimulative effect of calcitonin on cyclic AMP accumulation in avian bone in vitro.

The effect of calcitonin on the metabolism of calcium and cyclic AMP in the avian bone was examined in vitro. In the chick embryonic cortical bone, calcitonin affected neither the level of cyclic AMP nor the parathyroid hormone-induced stimulation of calcium release from bone. Also, the level of cyclic AMP in the cortical or medullary bone of Japanese quails was not increased by calcitonin. The medullary bone did not respond to calcitonin either in freshly prepared tissue or in tissue cultured for 48 hr in the absence of calcitonin. The activity of renal adenylate cyclase of Japanese quails was also calcitonin-insensitive. The inability of calcitonin to increase the level of cyclic AMP and to antagonize the parathyroid hormone-induced stimulation of calcium release from bone may account for the lack of hypocalcemic effect of calcitonin in birds as reported by other investigators.

Adenylyl Cyclases↗

Effect of DL-alpha-tocopherol (vitamin E) on the differentiation of mouse myeloid leukemia cell.

The effect of DL-alpha-tocopherol on the differentiation of the mouse myeloid leukemia cell line (M1) was investigated using fluorometry. The reliability of the fluorometric determination was verified by the mutual overlapping of the curves of disappearance of the radioactivity recovered as alpha-tocopherol and the loss of its fluorescence. alpha-Tocopherol solubilized into the culture medium was relatively stable (t1/2 = 147-168 hr). In corporation of alpha-tocopherol into M1 cells was time- and dose-dependent. Proliferation of M1 cells was never inhibited, but was slightly enhanced by treatment with alpha-tocopherol. alpha-Tocopherol caused a twofold increase in acid-phosphatase activity and slightly inhibited both the spontaneous- and dexamethasone-induced differentiation with respect to adhesion on glass and cell surface-rosette formation. alpha-Tocopherol also induced morphological change, making the shape of M1 cells rounder.

Animals↗

Regulation and its refractoriness of 25-hydroxyvitamin D3 metabolism in vitamin D deficiency.

The time course of change in plasma calcium levels and renal metabolism of 25-hydroxyvitamin D3 [25(OH)D3] was investigated in chicks maintained on a vitamin D-deficient diet for 4 weeks. Plasma calcium concentrations dropped sharply between the 7th and 14th day of the feeding period. Renal 25(OH)D3-1 alpha-hydroxylase activity was reciprocally enhanced concurrently with the decrease in plasma calcium levels. The elevated activity of 1 alpha-hydroxylase had declined significantly by the 21st and 28th days in spite of the more severe hypocalcemia. When graded amounts of vitamin D3 were administered to the chicks maintained on this diet for 14 or 28 days, there were considerable differences in the change of plasma calcium levels and 25(OH)D3 metabolism induced by vitamin D3 administration between the 14-day and 28-day birds. The minimal dose levels of vitamin D3 to completely suppress renal 1 alpha-hydroxylase activity were 25 micrograms in the 14-day, and 2.5 mg in the 28-day birds. These differences were not observed between the 14-day and 28-day birds when 1 alpha-hydroxyvitamin D3 [1 alpha(OH)D3] was administered. Renal adenylate cyclase activity induced by parathyroid hormone (PTH) was much lower in the 28-day chicks than that in 1-day-old and the 14-day birds. These results are explained by the hypersecretion of PTH and the subsequent refractoriness of the target organs in severe vitamin D deficiency. Plasma calcium levels per se did not appear to be a major factor in the regulation of 25(OH)D3 metabolism.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗

The production of putative osteoclasts in tissue culture - ultrastructure, formation and behavior.

A system for culture of cat bone marrow produces multinucleate cells (50-100 nuclei) of large proportions (300 micrometer diameter). Scanning and transmission electron microscopy indicates that these cells (not virally induced syncytia) are true osteoclasts, which exhibit ultrastructural aspects of bone resorption (ruffled border and clear zones in TEM section, active spatulate cytoplasmic extensions in the SEM) even after 6 weeks culture on a plastic substratum. Observations have also been made regarding the formation of the multinucleate cells from apparently specific mononuclear precursors, and the behaviour of these cells on various substrata is also reported.

Animals↗

A high-affinity cytosol binding protein for 1 alpha,25-dihydroxycholecalciferol in the uterus of Japanese quail.

Cytosol fractions prepared from the uterine mucosa of egg-laying Japanese Quail were analysed for binding of the metabolites of cholecalciferol. When the uterus was incubated at 37 degrees C with various radioactive metabolites of cholecalciferol, the nuclear fraction incorporated only 1 alpha,25-dihydroxy[3H]cholecalciferol. When the uterus was incubated at 0 degree C with 1 alpha,25-dihydroxy[3H]cholecalciferol, most of the radioactivity was found in the cytosol. Translocation of 1 alpha,25-dihydroxy[3H]cholecalciferol from the cytosol to the nucleus was temperature-dependent. The addition of 100-fold excess amounts of unlabelled 1 alpha-25-dihydroxycholecalciferol significantly diminished the nuclear binding of 1 alpha,25-dihydroxy[3H]cholecalciferol. The cytosol fraction contained a 3.5 S macromolecule that specifically binds 1 alpha,25-dihydroxy[3H]cholecalciferol. The dissociation constant was 0.39 nM and the maximal binding was 55 fmol/mg of protein. These results strongly suggest that the uterus in egg-laying birds is a target organ or 1 alpha,25-dihydroxycholecalciferol.

Animals↗