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Biomedical subjects

Y Nishii

Publications and source records attributed to Y Nishii.

At least 127 records · Page 7Linked to original sources
PubMed1982

1 alpha,25-Dihydroxycholecalciferol and a human myeloid leukaemia cell line (HL-60).

Human promyelocytic leukaemia cells (HL-60) can be induced to differentiate into mature granulocytes in vitro by 1 alpha,25-dihydroxycholecalciferol [1 alpha,25(OH)2D3], the active form of cholecalciferol. The differentiation-associated properties, such as phagocytosis and C3 rosette formation, were induced by as little as 0.12 nM-1 alpha,25(OH)2D3, and, at 12 nM, about half of the cells exhibited differentiation on day 3 of incubation. Concomitantly the viable cell number was decreased to less than half of the control. Among various derivatives of cholecalciferol examined, 1 alpha,25(OH)2D3 and 1 alpha,24R-dihydroxycholecalciferol were the most potent in inducing differentiation, followed successively by 1 alpha,24S-dihydroxycholecalciferol, 1 alpha-hydroxycholecalciferol, 25-hydroxycholecalciferol and 24R,25-dihydroxycholecalciferol. A cytosol protein specifically bound to 1 alpha,25 (OH)2D3 was found in HL-60 cells. Its physical properties closely resembled those found in such target tissues as intestine and parathyroid glands. 1 alpha,25(OH)2D3 bound to the cytosol receptor was transferred quantitatively to the chromatin fraction. The specificity of various derivatives of cholecalciferol in inducing differentiation was well correlated with that of their association with the cytosol receptor. These results are compatible with the hypothesis that the active form of cholecalciferol induces differentiation of human myeloid leukaemia cells by a mechanism similar to that proposed for the classical concept of steroid hormone action.

Binding Sites↗
PubMed1982

Chemical synthesis, biological activity, and metabolism of 25-hydroxy-24-oxovitamin D3.

25-Hydroxy-24-oxovitamin D3 (25(OH)24-oxo-D3), a metabolite of 25-hydroxyvitamin D3, has been chemically synthesized. The ultraviolet, mass, infrared, and proton nuclear magnetic resonance spectra of the 25(OH)24-oxo-D3 were identical with those of the natural product isolated from chick kidney incubates. The oxo compound showed biological activity similar to 24,25-dihydroxyvitamin D3 (24,25(OH)2D3) in vitamin D-deficient chicks in enhancing intestinal calcium transport and bone calcium mobilization activities. Although 25(OH)24-oxo-D3 partially restored the impaired eggshell weights of Japanese quails fed a vitamin D-deficient diet, it was much less potent than 25-hydroxyvitamin D3 or 1 alpha, 25-dihydroxyvitamin D3. In addition, there was no effect on the calcification of medullary bone. When 25(OH)24-oxo[3H]D3 was incubated with kidney homogenates from vitamin D-deficient chicks, it was metabolized to [3H]1 alpha, 24,25-trihydroxyvitamin D3 and a metabolite which was eluted in a region between authentic 24R,25(OH)2D3 and 1 alpha, 25-dihydroxyvitamin D3 on high pressure liquid chromatography. In the incubates of kidney homogenates from vitamin D-supplemented chicks, those metabolites were not detected. In vitamin D-supplemented chicks, the recovery of radioactivity in the chloroform phase extracted by the method of Bligh and Dyer was only 50%, while that in vitamin D-deficient chicks was 87%. Moreover, the radioactivity eluted in the 25(OH)24-oxo-D3 fraction from vitamin D-supplemented chicks was only one-fifth of that from vitamin D-deficient birds. The present results indicate that the 24-oxidation of 24,25(OH)2D3 may be a route of inactivation of vitamin D3.

Animals↗
PubMed1982

Distribution of ornithine decarboxylase activity induced by 1 alpha,25-dihydroxyvitamin D3 in chick duodenal villus mucosa.

The distribution of enzymes involved in polyamine synthesis and that of the polyamine levels were investigated in the duodenal mucosa of vitamin D-deficient chicks and those supplemented with 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25-(OH)2D3]. Duodenal epithelial cells were isolated sequentially from the villus tip to the crypt region using a nonenzymatic method. In vitamin D-deficient chicks, the activities of ornithine decarboxylase (ODC) and S-adenosylmethionine decarboxylase were markedly higher in the crypt cells than in the villus cells. Similar gradients were observed in the distribution of putrescine and spermidine. Six hours after iv administration of 625 ng 1 alpha,25-(OH)2D3, ODC activity and putrescine levels markedly increased both in the villus and crypt region. The rate of the increase in ODC activity and putrescine levels, however, was much higher in the villus than in the crypt region. Neither S-adenosylmethionine decarboxylase activity nor spermidine levels were affected by the treatment with 1 alpha,25-(OH)2D3. To investigate differential uptake of 1 alpha,25-(OH)2D3 in the duodenal mucosa, 0.1 nmol 1 alpha,25-(OH)2[3H]D3 with or without a 200-fold excess of unlabeled 1 alpha,25-(OH)2D3 was injected into rachitic chicks, and epithelial cells were sequentially isolated 2 h later. The radioactivity specifically incorporated in the nuclear fraction was distributed uniformly from the villus tip to crypt cells. The cytoplasmic receptor for 1 alpha,25-(OH)2D3 was similarly distributed in the crypt and villus cells. These results suggest that 1 alpha,25-(OH)2D3 plays a physiological role in cellular activities not only in the villus but also in the crypt region through polyamine biosynthesis.

Adenosylmethionine Decarboxylase↗
PubMed1981

Ornithine decarboxylase activity in chick duodenum induced by 1 alpha, 25-dihydroxycholecalciferol.

The effect of cholecalciferol and its metabolites on ornithine decarboxylase activity was investigated in the duodenal mucosa of vitamin D-deficient chicks. The duodenal ornithine decarboxylase activity decreased in animals fed a vitamin D-deficient diet and its retarded activity was increased dose-dependently by a single injection of cholecalciferol. Among various metabolites of cholecalciferol tested, 1 alpha, 25-dihydroxycholecalciferol [ 1 alpha, 25 (OH)2D3] was the most potent stimulator. Stimulation of the enzyme activity was detected as early as 2h after intravenous administration of 1 alpha, 25 (OH)2D3 and a maximal value was attained at 6 h. The maximal value was 27 times higher than the control. In addition, treatment with 1 alpha 25 (OH)2D3 affected the duodenal content of polyamines. The content of putrescine increased to a value of three times that of the control 6 h after the hormone administration. The spermidine content did not change appreciably. The enhancement of duodenal ornithine decarboxylase activity by 1 alpha, 25 (OH)2D3 occurred in parallel with the enhancement of calcium absorption, which was first detected 3 h after the hormone administration. The enhancement appeared to be tissue-specific. It was observed in every intestinal segment, but was highest in the duodenum. Enzyme activity in other tissues was not influenced appreciably by 1 alpha, 25 (OH)2D3. These results clearly indicate that the duodenal biosynthesis of polyamines is regulated by 1 alpha, 25 (OH)2D3, suggesting the possibility that duodenal ornithine decarboxylase may be involved in the calcium absorption mechanism.

Animals↗
PubMed1981

Isolation, identification, and biological activity of 25-hydroxy-24-oxovitamin D3: a new metabolite of vitamin D3 generated by in vitro incubations with kidney homogenates.

A metabolite of 25-hydroxyvitamin D3 has been isolated in pure form from incubation mixtures containing kidney homogenates of chicks given large doses of vitamin D3. The isolation involved methanol--chloroform extraction and six steps of column chromatography. The metabolite was identified as 25-hydroxy-24-oxovitamin D3 by means of ultraviolet absorption spectrometry, mass spectrometry, infrared spectrometry, nuclear magnetic resonance spectrometry, and specific chemical reactions. Use of a sensitive in situ technique revealed that 25-hydroxy-24-oxovitamin D3 enhances intestinal calcium transport in rats approximately as effectively as 24,25-dihydroxyvitamin D3 does. In contrast, 25-hydroxy-24-oxovitamin D3 appeared to be less active than 24,25-dihydroxyvitamin D3 in chicks 24 h after intravenous injection.

Animals↗
PubMed1981

A survey of impatient alcoholics in Okayama and Kochi Prefectures.

A survey of inpatient alcoholics was conducted in Okayama and Kochi prefectures in 1977 and 1979. The total number of inpatient alcoholics was 230 in Okayama and 401 in Kochi, Corresponding to 5.5% and 10.7% of the total number of inpatients in psychiatric hospitals, respectively. The percentage of female alcoholics was 6.6% in Okayama and 6.5% in Kochi. By age distribution, the percentage of elderly alcoholics was high, but young alcoholics in their 20s were extremely few. As for the marital state, the spouseless situation showed a high percentage. Regarding the defrayment of medical expenses, half of the patients were on relief. Alcoholics staying in hospital for a year or longer accounted for nearly one-half of the cases. Classification of the subtypes of alcoholism revealed that the problem drinking group accounted for the majority with over 60%, indicating that many cases of social problems were brought to the hospital.

Adult↗
PubMed1980

Metabolites of 24,25-dihydroxyvitamin D3 made in the kidney of chicks supplemented with vitamin D3.

Metabolism of 25-hydroxyvitamin D3 (25-OH-D3) was examined in chicks supplemented with vitamin D3. Kidney homogenates metabolized in vitro [3H]-25-OH-D3 to 3 new metabolites (peaks A, C and E) by way of 24,25-dihydroxyvitamin D3. The enzymes responsible for the synthesis of these metabolites appeared to be induced by 1 alpha,25-dihydroxyvitamin D3. Production of these metabolites was increased in parallel with the increase of the supplemented levels of vitamin D3, while recovery of the radioactivity in the chloroform phase was sharply decreased. The production of peak C was considered to be closely related to the transfer of the radioactive metabolites to the water-soluble phase. These results may indicate that 24-hydroxylation is a degradation step in the 25-OH-D3 metabolism.

24,25-Dihydroxyvitamin D 3↗
PubMed1980

Vitamin D and parathyroid hormone degradation by the kidney.

Parathyroid function is controlled by the regulation of hormone secretion as well as degradation, through the action of calcium and vitamin D derivatives. In order to clarify the relationship between vitamin D metabolism and parathyroid degradation system, parathyroid hormone (PTH)-degrading activities of the kidney were measured in vitamin D repleted and depleted rats given various derivatives of vitamin D. Kidney calcium content rose markedly in animals given 10 microgram/kg 1 alpha(OH) vitamin D3 and 1,000 microgram/kg dihydrotachysterol and PTH-degrading activity rose only in these animals, indicating a parallelism between kidney calcium content and PTH-degrading activity of the kidney tissue. These vitamin D derivatives also increased the PTH-degrading activity of kidney tissue when they were added in vitro.

Animals↗
PubMed1980

Vitamin D and vitamin D dependency.

Administration of large doses of vitamin D2 brought about a marked increase of 25-hydroxyvitamin D in both the patients with vitamin D dependency and hypophosphatemic vitamin D-resistant rickets. During the administration of vitamin D2, increment of 1,25-dihydroxyvitamin D was marked in hypophosphatemic vitamin D-resistant rickets, but far smaller in vitamin D dependency. In the latter, however, the 1,25-dihydroxyvitamin D reached the level close to the normal adult values. 1 alpha-hydroxyvitamin D3 was found 50 approximately 100 times as effective as vitamin D2 in 2 patients with vitamin D dependency (optimum maintenance dose: 0.05 micrograms/kg/day). It was concluded that 1 alpha-hydroxylation in the renal tubules is markedly defective in the patients with vitamin D dependency, but that a large dose of vitamin D2 is able to cause a definite increase in serum concentration of 1,25-dihydroxyvitamin D resulting in improvement of the rickets.

Alkaline Phosphatase↗
PubMed1980

Osseous changes and abnormalities of mineral metabolism in rats with glycopeptide-induced nephritis.

A laboratory model of renal osteodystrophy was developed in rats by a single injection of glycopeptide isolated from renal cortical tissues of rats according to the method used by Shibata et al. to induce glomerulonephritis. Approximately 60-70 days after injection, severe proteinuria appeared and continued for at least 170 days at a rate of more than 1 g/day. Morphological changes in the kidney were typical of chronic glomerulonephritis. The plasma calcium concentration was lowered transiently by the 96th day after injection, but was restored to the normal range thereafter. Plasma parathyroid hormone levels, however, continued to rise in parallel with the degree of proteinuria. Marked secondary hyperparathyroidism was induced which led to severe bone atrophy. Histological examinations showed a marked increase of resorbing cavities, with a quantitatively larger number of osteoclasts in cortical bone tissues compared with the control animals. No spontaneous remission was observed. It is emphasized that all of the biochemical and morphological changes reported here were induced by a single injection of homologous renal glycopeptide, and they were highly reproducible.

Animals↗
PubMed1980

Comparative therapeutic effects of vitamin D3 and its derivatives on experimental renal osteodystrophy.

The comparative effectiveness of vitamin D3 and its derivatives in curing hyperparathyroidism and osteodystrophic bone lesions was examined in a laboratory model of renal osteodystrophy associated with marked secondary hyperparathyroidism in rats. The experimental model was prepared by a single injection of homologous glycopeptide. Plasma levels of 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] appeared to decrease in the rats receiving glycopeptide. Various doses of vitamin D3 derivatives [2 or 10 microgram/kg D3, 2 microgram/kg 25-hydroxyvitamin D3 (25OHD3), 0.1 microgram/kg 1 alpha,25(OH)2D3, and 0.1 or 0.2 microgram/kg 1 alpha-hydroxyvitamin D3 (1 alpha OHD3)] were daily administered orally to the nephritic rats for 23 days before sacrifice. 1 alpha,25(OH)2D3 and 1 alpha OHD3 were much more potent than 25OHD3 and D3 in reducing the hyperplasia of parathyroir glands. The potency of 1 alpha OHD3 in curing the histological changes of osteodystrophy appeared to be greater than that of 1 alpha,25(OH)2D3. The same dose level of 1 alpha OHD3 was more effective than 1 alpha,25(OH)2D3 in enhancing plasma 1 alpha,25(OH)2D3 levels.

Animals↗
PubMed1978

Anxiety symptoms of the patients with aortic arch syndrome.

We reported six cases of the aortic arch syndrome with brain symptoms. Two could be explained directly as an organic impairment of the brain. In the remaining four cases, however, the mental symptoms were considered to have a basis of "anxiety." They were easily precipitated by iatrogenic and other various environmental factors. The hyperventilation syndrome had a high incidence occurring in three out of the four cases of anxiety. Thus, it seems appropriate to interpret their symptoms psychosomatically. The production of brain symptoms may be due to psychosomatic mechanisms in many cases of the aortic arch syndrome.

Adult↗