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Biomedical subjects

N Horiuchi

Publications and source records attributed to N Horiuchi.

At least 91 records · Page 5Linked to original sources
PubMed1985

The mechanism of end-organ resistance to 1 alpha,25-dihydroxycholecalciferol in the common marmoset.

The common marmoset, a New World monkey, requires a large amount of cholecalciferol (110 i.u./day per 100g body wt.) to maintain its normal growth. In a previous report, we demonstrated that the circulating levels of 1 alpha, 25-dihydroxycholecalciferol [1 alpha,25(OH)2D3] in the marmosets are much higher than those in rhesus monkeys and humans, but the marmosets are not hypercalcaemic [Shinki, Shiina, Takahashi, Tanioka, Koizumi & Suda (1983) Biochem. Biophys. Res. Commun. 14, 452-457]. To compare the effect of the daily intake of cholecalciferol, two rhesus monkeys were given a large amount of cholecalciferol (900 i.u./day per 100g body wt). Their serum levels of calcium, 25-hydroxycholecalciferol and 24R,25-dihydroxycholecalciferol were markedly elevated, but the serum 1 alpha,25(OH)2D3 levels remained within a range similar to those in the rhesus monkeys fed the normal diet (intake of cholecalciferol 5 i.u./day per 100g body wt). Intestinal cytosols prepared from both monkeys contained similar 3.5 S macromolecules to which 1 alpha,25(OH)2D3 was bound specifically. However, the cytosols from the marmosets contained only one-sixth as many 1 alpha,25(OH)2D3 receptors as those from the rhesus monkeys. Furthermore, the activity of the 1 alpha,25(OH)2D3-receptor complex in binding to DNA-cellulose was very low in the marmosets. These results suggest that the marmoset possesses an end-organ resistance to 1 alpha,25(OH)2D3 and is a useful animal model for studying the mechanism of vitamin D-dependent rickets, type II.

Animals↗
PubMed1985

1 alpha,25-dihydroxyvitamin D3 receptors and their action in embryonic chick chondrocytes.

The role of vitamin D in the maturation of epiphyseal chondrocytes was investigated in the developing chick embryo. Cartilage tissues were divided into two parts: resting cartilage and growth cartilage. A cytosol component to which 1 alpha,25-dihydroxyvitamin D3 (1 alpha,25(OH)2D3) is specifically bound first appeared in the growth cartilage on day 15, rapidly increased, and attained a maximum on day 19. The calcium content of the growth cartilage also began to increase on day 15 and continued to increase in parallel with the 1 alpha,25(OH)2D3 receptor levels. Glycosaminoglycan (GAG) synthesis by the growth cartilage cells increased from day 11-17 and rapidly declined thereafter reciprocally with the increase in calcium and receptor levels. In the resting cartilage, no cytosol receptor for 1 alpha,25(OH)2D3 was detected up to hatching time. The calcium content and GAG synthesis in the resting cartilage were very low and did not change appreciably throughout development. No receptor-like macromolecule for 24R,25-dihydroxyvitamin D3 (24R,25(OH)2D3) was recognized in either the resting or growth cartilage. 1 alpha,25(OH)2D3 added to the culture of chondrocytes from the epiphyseal growth cartilage inhibited GAG synthesis and stimulated its release from the cell layer into the medium in a dose-dependent manner. These in vitro effects of 1 alpha,25(OH)2D3 were not observed in chondrocytes obtained from 13-day-old growth cartilage and 19-day-old resting cartilage. 25-Hydroxyvitamin D3 and 24R,25(OH)2D3 had no effect on chondrocytes in any of the preparations. These results suggest that 1 alpha, 25 (OH)2D3 is directly involved in the maturation of chondrocytes and possibly in the calcification of growth cartilage.

Animals↗
PubMed1985

Causes of death in Japanese diabetics. A 20-year study of death certificates.

Death certificates filed between 1960 and 1979 in Osaka, Japan were analyzed to study causes of death in diabetic patients. It was observed that diseases of the circulatory system increased continuously from 15.2% in 1960-1964 to 27.2% in 1975-1979. Cerebrovascular disease and disease of heart were the leading causes of death throughout the study period. The rate of increase was much faster for disease of heart than for cerebrovascular disease, and there was only a small difference between them as cause of death in diabetic patients at the end of the observation period. Malignant neoplasms, cirrhosis of the liver, and pneumonia and bronchitis increased, whereas tuberculosis decreased sharply according to age-adjusted mortality rate during the 20-year period. Analysis based on O/E ratios suggested higher risk of dying from ischemic heart disease, tuberculosis and cirrhosis of the liver in Japanese diabetics than in the general population in this country.

Aged↗
PubMed1985

Differences in the side-chain metabolism of vitamin D3 between chickens and rats.

In vitro metabolism of 25-hydroxy-24-oxovitamin D3 was studied in kidney homogenates from vitamin D-supplemented chickens and rats. In chicken homogenates, 25-hydroxy-24-oxovitamin D3 was converted predominantly to 23,25-dihydroxy-24-oxovitamin D3, 24,25-dihydroxyvitamin D3, and 23,24,25-trihydroxyvitamin D3. In rat homogenates, 25-hydroxy-24-oxovitamin D3 was not converted to either 24,25-dihydroxyvitamin D3 or 23,24,25-trihydroxyvitamin D3, but it was converted to 23,25-dihydroxy-24-oxovitamin D3 and 23-hydroxy-24,25,26,27-tetranorvitamin D3. The latter metabolite was not produced by the chicken preparations. The stereochemical configuration at C-24 of the 24,25-dihydroxyvitamin D3 produced by chicken homogenates was determined to be S. This contrasts with the R configuration of 24,25-dihydroxyvitamin D3 produced by 24-hydroxylation of 25-hydroxyvitamin D3. These results suggest that chickens have an enzyme that can reduce the 24-oxo group to 24S-hydroxyl group, whereas rats do not.

Animals↗
PubMed1985

Detection and developmental changes of the 1,25-(OH)2-D3 receptor concentration in mouse skin and intestine.

We investigated [3H]1,25-dihydroxyvitamin D3-specific binding activity in fetal, neonatal, and adult mouse skin to determine (a) during which stage in development the skin develops the capacity to respond to this hormone and (b) whether the hormone binding activity changed during development and maturation. A macromolecule with properties similar to those of the chick intestinal 1,25-dihydroxyvitamin D3 receptor was detected in the skin and intestine of mouse pups at 17 days of fetal life. 1,25-Dihydroxyvitamin D3-specific binding activity from both tissues sedimented on linear sucrose gradients at 3.5-3.7S and eluted from DNA cellulose at 0.22 M KCl. At earlier stages of fetal life (12-14 days) receptor-like activity was detected in cytosols prepared from whole-mouse fetuses. 1,25-Dihydroxyvitamin D3-specific binding activity was quantitated in the skin and intestine throughout development using a chromatin binding assay. Scatchard analysis of saturation binding data showed that the concentration of binding activity in skin increased rapidly after birth and reached a maximum when the mice were 10-19 days old. By contrast, the binding activity that was detected in the fetal and neonatal whole intestine remained low until the mice were weaned. The affinity (Kd) of the binding activity was similar in skin and intestine at all ages studied. It is concluded that 1,25-dihydroxyvitamin D3-specific binding activity appears in both skin and intestine of the mouse prior to birth and increases in these two tissues during different stages in development.

Animals↗
PubMed1985

Diabetic osteopenia in central Japan.

A large scale study of diabetic osteopenia was conducted in central Japan. The degree of bone mass loss was measured in 1267 diabetic patients and 646 control subjects. Based on six indices obtained by microdensitometry, the bone mass of 21.1% of the diabetic patients was found to be markedly decreased and that of 8.2% was found to be severely decreased, while only 7.9% of the control group showed bone mass loss. The prevalence of diabetic osteopenia in female patients was significantly higher than in males, but a positive correlation between the degree of bone mass loss and age was observed in both the male and female patients. Patients requiring oral agents or insulin had significantly more bone mass loss than those on dietary therapy alone.

Adolescent↗
PubMed1984

A rapid and sensitive in vitro assay of 25-hydroxyvitamin D3-1 alpha-hydroxylase and 24-hydroxylase using rat kidney homogenates.

A sensitive and rapid in vitro assay of 25-hydroxyvitamin D3 [25-(OH)D3]-1 alpha- and 24-hydroxylase activities was developed using rat kidney homogenates. A potent inhibitor of the enzymes in rat plasma was removed by thoroughly perfusing rats with saline. Kidney homogenates prepared from vitamin D-deficient rats preferentially produced tritiated 1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] from 25(OH) [3H]D3. Addition of 10 microliter or more of rat plasma to 3 ml of 10% kidney homogenates suppressed 1 alpha-hydroxylase activity dose-dependently. Thyroparathyroidectomy (TPTX) of vitamin D-deficient rats greatly abolished 1 alpha-hydroxylase activity. Administration of parathyroid hormone to the TPTX rats increased 1 alpha-hydroxylase activity and that of 1 alpha,25(OH)2D3 enhanced 24-hydroxylase markedly. Since this assay is technically simple, rapid and sensitive, it will be useful in studying the regulatory mechanism in the renal metabolism of 25(OH)D3 in mammals.

25-Hydroxyvitamin D3 1-alpha-Hydroxylase↗
PubMed1983

A parathyroid hormone inhibitor in vivo: design and biological evaluation of a hormone analog.

A synthetic analog of bovine parathyroid hormone (bPTH), [tyrosine-34] bPTH-(7-34)NH2, was found to inhibit parathyroid hormone action in vivo. When the analog and parathyroid hormone were infused simultaneously to rats at a molar ratio of 200 to 1, the analog inhibited the excretion of urinary phosphate and adenosine 3',5'-monophosphate. When infused alone at the same dose rate, the analog was devoid of agonist activity. The compound was prepared by following design principles developed for inhibitors of parathyroid hormone, and is believed to be the first antagonist of parathyroid hormone that is effective in vivo.

Amino Acid Sequence↗
PubMed1983

A long-term follow-up study of Japanese diabetic patients: mortality and causes of death.

A systematic 20-year follow-up study of 1,221 diabetic patients was carried out in Osaka, Japan. The mean annual mortality rates were 2.55% for men and 1.64% for women. The ratios of observed to expected numbers of deaths were 1.50 for men and 1.39 for women, indicating an excess mortality for diabetic patients of both sexes, and higher mortality in men than in women. Factors that predisposed diabetic patients to premature death were early age of onset, albuminuria, diabetic retinopathy and fasting glucose level greater than 11.1 mmol/l at the initial examination. Insulin dependence was also associated with poor prognosis. Cerebro-cardiovascular and renal diseases were the major causes of death in the diabetic patients; heart disease was the cause of death in 16.9%, cerebrovascular disease in 16.4% and renal disease in 11.9%. The relatively high incidence of renal disease as cause of death in diabetic patients was striking. Malignant neoplasms of liver and of pancreas and cirrhosis were also associated with increased ratio of observed to expected number of deaths in the patients.

Age Factors↗
PubMed1983

The role of vitamin D in the medullary bone formation in egg-laying Japanese quail and in immature male chicks treated with sex hormones.

The effect of vitamin D3 on medullary bone formation was investigated in egg-laying Japanese quail and in immature male chicks treated with sex hormones. When laying quail were fed a vitamin D-deficient diet for 16 days, their eggshell weights and egg production rate were markedly reduced in a time-dependent manner with a significant decrease in plasma calcium and 25-hydroxyvitamin D3 levels. The calcium content of the medullary bone of femurs decreased markedly with the progress of vitamin D deficiency, whereas that of the cortical bone remained unchanged. Quantitative histological examination also showed that the area of the mineralized portion of medullary bone in quail that were fed the vitamin D-deficient diet markedly decreased compared with that in the control laying quail, whereas the total area of the mineralized and unmineralized portions of medullary bone in the bone marrow cavity increased moderately. Daily administration of vitamin D3 (0.75 microgram/day) to the vitamin D-deficient quail increased the mineralization of medullary bone as early as day 4. Daily administration of both estradiol (0.3 mg/day) and testosterone (0.9 mg/day) for 3 weeks to immature male chicks induced an apparent hypercalcemia and matrix formation of medullary bone, regardless of the vitamin D status of the chicks. Mineralization of medullary bone was observed only when vitamin D3 was administered together with the sex hormones. These results suggest that vitamin D3 is directly involved in the mineralization of medullary bone in birds.

Animals↗
PubMed1983

A multiresponse parathyroid hormone assay: an inhibitor has agonist properties in vivo.

Vitamin D-deficient rats subjected to thyroparathyroidectomy (TPTX) were used to evaluate in vivo the biological properties of native bovine parathyroid hormone (bPTH) and chemically synthesized fragments and analogues of the hormone on several parameters of hormone action: calcium and phosphorus fluxes, generation of cyclic adenosine 3',5'-monophosphate (cAMP), and the metabolism of 25-hydroxyvitamin D3 [25(OH)D3]. Vitamin D-deficient rats, after TPTX or sham operation, were intravenously infused with a nutrient containing 7.5 mM CaCl2 for 30 h. During the last 7 h, PTH or one of its analogues was infused intravenously at rates between 0.04 and 20 nmol/h. One hour after the start of the peptide infusion, tritiated 25(OH)D3 was injected. Urine was collected hourly for phosphate and cAMP determinations and, at the end of the experiment, blood was obtained to determine the relative accumulation of tritiated 1,25-dihydroxyvitamin D3 ([3H]1,25(OH)2D3). Infusion of bPTH-(1--84), bPTH-(1--34), human (h)PTH-(1--34), or [Nle8, Nle18, Tyr34]bPTH-(1--34) amide was accompanied by a comparable dose-dependent decrease in plasma phosphate and a dose-dependent increase in plasma calcium and [3H]-1,25(OH)2D3, and urinary excretion of phosphate and cAMP. An evaluation of [Nle8, Nle18, Tyr34]bPTH-(3--34) amide, a potent inhibitor of PTH action in vitro in the renal adenylate cyclase assay, revealed that the analogue possessed weak agonist properties in vivo. The analogue increased excretion of both cAMP and phosphate in the urine, decreased plasma phosphate levels, and increased the accumulation of [3H]-1,25(OH)2D3 in the plasma. This multiparameter model system should aid in the elucidation of the in vivo biological effects of PTH and its analogues.

Animals↗
PubMed1983

A long-term follow-up study of diabetic patients in Osaka, Japan: mortality and causes of death.

A long-term follow-up study of diabetic patients was carried out in Osaka, Japan. The subjects were 1,850 diabetics, who were first seen at our hospital between 1960-1979, and they were followed up until the end of 1980. Both the mean annual mortality rate and the O/E ratio indicated an excess mortality in diabetic patients compared to the general population, and a higher mortality in males than in females. Factors related to the prognosis of the subjects were elevated systolic blood pressure, albuminuria and elevated fasting glucose levels at the baseline, and poor metabolic control and insulin treatment during the follow-up period. Cerebrocardiovascular and renal diseases accounted for nearly half of all deaths. When compared to the expected death rate, the increase in the number of deaths due to renal disease was remarkable. Malignant neoplasms also exhibited an increase in the O/E ratio, and were responsible for one quarter of all deaths. In particular, an increase in cancer of the liver and of the pancreas was noted. In addition, an increased O/E ratio was observed for cirrhosis of the liver.

Aged↗