Simultaneous evaluations of 1,25-dihydroxyvitamin D3 receptors in fresh layers of epidermis and dermis from normal rat skin--separation of the two sheets by dispase treatment.
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Biomedical subjects
Publications and source records attributed to S Imanaka.
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The effect of estrogens on the renal responsiveness to parathyroid hormone (PTH) was examined by PTH loading tests with synthetic human-PTH (1-34) in 8 normal elderly females (mean +/- SD age, 81.0 +/- 7.1 yr) before and after administration of estrogen (Premarin 1.25 mg/day for 4 weeks). Basal urinary adenosine cyclic 3', 5'-monophosphate (cAMP) excretion showed a tendency to increase after estrogen administration (5.47 +/- 1.68 vs 6.60 +/- 2.67 nmol/100 ml GFR) and the theoretical renal phosphorous threshold showed a tendency to decrease from 3.22 +/- 0.98 to 2.73 +/- 0.56 mg/dl. The blood ionized calcium concentration did not change after estrogen administration (4.44 +/- 0.16 vs 4.32 +/- 0.20 mg/dl) and serum phosphorous (P) decreased significantly (3.65 +/- 0.47 vs 3.01 +/- 0.42 mg/dl, p less than 0.05). There was no increase in mean serum immunoreactive PTH (0.34 +/- 0.10 vs 0.34 +/- 0.05 ngeq/ml). The urinary excretions of cAMP in response to PTH loading [100 U of human-PTH (1-34), intravenously] significantly (p less than 0.05) increased (94.8 +/- 57.0 vs 196.7 +/- 118.3 nmol/100 ml GFR/h) after estrogen administration. Moreover the changes in urinary excretion of cAMP (r = 0.698, p less than 0.01) and P (r = 0.555, p less than 0.05) induced by the PTH loading were positively correlated with serum estradiol in elderly females, assessed as groups before and after estrogen administration. These results suggest that estrogens may enhance the renal responsiveness to exogenous PTH administration.
A male patient with hypogonadotropic hypogonadism has been treated by pulsatile administration lf luteinizing hormone-releasing hormone (LHRH) (20-25 micrograms, every 2 hours, sc) for 4 years 6 months. His plasma testosterone (T) concentration began to increase after 4 weeks of treatment and reached the normal range in week 5. He showed complete secondary sexual development after 1 year of treatment. His sperm count was normalized after 1 year of treatment. He was married after 29 months of therapy, and has a healthy male child. Blood type tests showed his paternity of the child. During the long duration of pulsatile LHRH therapy, his gonadotropin secretion has been stimulated by LHRH and his T level has been maintained with no observable side effects. There are no other reports of patients treated by pulsatile LHRH injection for such a long duration, but finding in this patient indicated that long-term pulsatile LHRH therapy is a useful and safe method for treatment of hypothalamic hypogonadotropic hypogonadism.
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The influence of nicorandil, a potent antianginal drug, on cellular calcium in vascular smooth muscle cells (VSMC) was investigated by studying its effects on the cytosolic free calcium concentration ([Ca2+]i) and calcium-stimulated magnesium-dependent ATPase [(Ca2+ + Mg2+)-ATPase] in the cells. VSMC were prepared from rat aorta, and their [Ca2+]i level was determined by measuring the fluorescence of the free calcium indicator, fura 2. Preincubation with nicorandil for 5 min significantly decreased the rise in [Ca2+]i evoked by addition of either angiotensin II in control solution or prostaglandin F2 alpha, the latter in either the presence or absence of extracellular calcium. The effect of nicorandil on (Ca2+ + Mg2+)-ATPase activity in the microsomal fraction of porcine coronary artery smooth muscle, which is rich in plasma membranes and sarcoplasmic reticulum, was also investigated. Nicorandil at concentrations of 10(-6) and 10(-5) M increased the activity of (Ca2+ + Mg2+)-ATPase significantly at a free calcium concentration of 0.3 microM. At 10(-6) M, nicorandil significantly decreased the Kd for calcium of this enzyme without significantly changing its Vmax. These data suggest that nicorandil suppressed increase of [Ca2+]i, possibly by stimulating (Ca2+ + Mg2+)-ATPase, thereby inhibiting contraction of vascular smooth muscle.
Parathyroid hormone is reported to be a possible causal factor of abnormalities of electroencephalograms of patients with renal failure. In this study, the parathyroid hormone levels were compared in the circulation and cerebrospinal fluid of seven normal subjects and 22 patients with renal failure including those who showed abnormal electroencephalograms. The circulating levels of both C-terminal and N-terminal parathyroid hormone in the subjects studied showed a positive correlation (C-terminal, r = 0.58, P less than 0.01; N-terminal, r = 0.61, P less than 0.01) with the grade of abnormality of the electroencephalogram. However, the levels of C-terminal and N-terminal parathyroid hormone in the cerebrospinal fluid of both normal subjects and patients with renal failure were below the detectable limit (C-terminal, less than 0.1 ng/ml; N-terminal, less than 2.3 pg/ml). These data suggest that in patients with renal failure, the effect of parathyroid hormone on the central nervous system is mediated in some other way than via the cerebrospinal fluid.
The effects of prostaglandin (PG) F2 alpha and 9,11-epithio-11,12-methanothromboxane A2 (STA2), a stable analogue of thromboxane A2, on the cytosolic free calcium concentration ([Ca2+]i) in vascular smooth muscle cells were studied with a new fluorescent Ca2+ indicator fura 2. PGF2 alpha and STA2, which are strong vasoconstrictors, caused rapid phasic and subsequent tonic increases in [Ca2+]i. PGF2 alpha caused dose-dependent elevation of [Ca2+]i not only in control solution but also in the calcium-free solution. A first stimulation with PGF2 alpha caused dose-dependent decrease in the response of [Ca2+]i to a second stimulation with PGF2 alpha. Pretreatment with 13-Azaprostanoic acid, a receptor level antagonist of thromboxane A2 inhibited the increase of [Ca2+]i induced by STA2. These results suggest that PGF2 alpha induces calcium mobilization followed by smooth muscle contraction through its specific receptors.
In an open-design study 1 alpha-hydroxyvitamin D3 was administered orally to 17 patients with psoriasis vulgaris at a dose of 1.0 micrograms/day for 6 months. More than moderate improvement was observed in 13 (76%) of the 17 patients from 2.7 +/- 0.6 months (mean +/- SD) after the start of treatment. No side effects of the treatment were observed. The mechanism of the effect of 1 alpha-hydroxyvitamin D3 requires study, but these data suggest that its oral administration is effective for treatment of psoriasis vulgaris.
We carried out a clinical trial of 1 alpha-hydroxycholecalciferol [1 alpha(OH)D3] at a dose of 1.0 microgram a day on 7 patients with psoriasis vulgaris. These patients had been treated by topical applications of corticosteroids before this study without improvement, and during the clinical trial, treatment of topical corticosteroids was continued on 6 of the 7 patients. Four of 7 patients showed complete remission and marked improvement and 2 additional patients showed minimal improvement of their skin lesions during and after the treatment with 1 alpha(OH)D3. No adverse reactions were noted during the treatment period. The mechanism of the phenomenon we observed has yet to be elucidated. Controlled trials of large numbers of patients with psoriasis vulgaris treated with 1 alpha(OH)D3 are under way.
The effects of topical administration of 1,25-dihydroxyvitamin D3, as 0.1 and 0.5 microgram per g base, and control base applied to contralateral skin lesions in five patients with persistent psoriasis were compared. In all five, definite and in some cases remarkable improvement of the lesions was seen when 1,25-dihydroxyvitamin D3 at concentration of 0.5 microgram per g base was applied for two to five weeks. No local or systemic toxicity was detected in any patient. Although the mechanism of the improvement is yet to be elucidated, these results show the possible effectiveness of topical 1,25-dihydroxyvitamin D3 on psoriatic skin lesions.
The effects of synthetic [Asu1,7]-eel calcitonin (0.5 MRC unit/kg body weight intravenously for 30 min) on circulating levels of human calcitonin, calcium and gastrin were investigated in five patients with medullary carcinoma of the thyroid. Blood samples were obtained before and 15, 30, 60, 90, 120 and 180 min after commencement of infusion of [Asu1,7]-eel calcitonin. Plasma levels of human calcitonin were measured by radioimmunoassay. Cross-reactivity with [Asu1,7]-eel calcitonin in this assay was negligible. On infusion of [Asu1,7]-eel calcitonin, the mean plasma level of human calcitonin decreased significantly to 71.0 +/- 8.7% of the basal level (mean +/- SEM, P less than 0.05) after 30 min and 68.4 +/- 25.4% of the basal level (P less than 0.05) after 60 min. The serum calcium level also decreased significantly, but lagged behind the decrease of human calcitonin, being 95.1 +/- 0.7% of the basal level (P less than 0.01) at 120 min and 94.8 +/- 0.6% of the basal level (P less than 0.02) at 180 min. The mean plasma gastrin level did not change significantly on infusion of [Asu1,7]-eel calcitonin. In pooled data for all times, the percentage change in human calcitonin was not significantly correlated with either the percentage change in calcium (r = -0.25, P greater than 0.1) or the percentage change in gastrin (r = -0.38, P greater than 0.1).
Active forms of vitamin D3, 1 alpha-hydroxyvitamin D3 and 1 alpha,25-dihydroxyvitamin D3, were administered in an open-design study to 40 patients with psoriasis vulgaris in three ways: to 17 patients 1 alpha-hydroxyvitamin D3 was given orally at a dose of 1.0 micrograms/day for 6 months, to four patients 1 alpha,25-dihydroxyvitamin D3 was given orally at a dose of 0.5 microgram/day for 6 months, and 19 patients were given 1 alpha,25-dihydroxyvitamin D3 applied topically at concentration of 0.5 microgram/g of base for 8 weeks. Improvement was observed at the end of the individual study periods in 13 (76%) patients in Group 1 with a mean period of treatment (+/- SD) of 2.7 +/- 0.6 months, in one patient in Group 2 at 3 months after the start of treatment, and in 16 (84%) patients in Group 3 when the chemical was applied for 3.3 +/- 1.2 weeks. No side-effects were observed in any of these trials. These data suggest that psoriasis may respond to active metabolites of vitamin D3 and that abnormalities in vitamin D metabolism or in responsiveness of the skin cells to active metabolites of vitamin D may be involved in the pathogenesis of this skin disease.
Calcitonin-like immunoreactivity levels were determined in urine specimens in 585 normal subjects of various ages. Urine calcitonin-like immunoreactivity (uCTi) was measured by the midportion-specific radioimmunoassay after extraction of urine by gel chromatography on a 0.8 X 20 cm column of Bio Gel P-2. In 197 males and 169 females below 20 years old, significant negative correlations between the age and uCTi were observed (male: r = -0.684, female: r = -0.690). In 75 males and 80 females above 41 years, however, no significant correlation was observed between age and uCTi. The high level of uCTi in children could be explained by high levels of circulating calcitonin, associated with rapid bone growth; however the uCTi level in the elderly may not reflect the physiological significance of calcitonin for them because of a suspected age-related decrease in renal clearance of uCTi in the elderly.
This report describes a 78-year-old woman with insulinoma, treated with a combination of diphenylhydantoin and a calcium antagonist. The effectiveness of 200 mg of diphenylhydantoin and 180 mg of diltiazem was evaluated by measuring the levels of plasma glucose, immunoreactive insulin and immunoreactive insulin/plasma glucose after fasting or by the oral glucose tolerance test, and by the appearance of hypoglycemic symptoms. The mean concentration of fasting plasma glucose increased significantly during the treatment. The levels of immunoreactive insulin/plasma glucose and C-peptide immunoreactivity/plasma glucose significantly decreased. Symptomatically, no episode of hypoglycemia was noted during the combined treatment.
A parathyroid hormone (PTH) loading test with synthetic human PTH(1-34) was performed in 7 young and 6 elderly normal males. The elderly subjects had significantly higher mean basal levels of serum PTH than the young subjects (0.262 +/- 0.035(SE) vs 0.097 +/- 0.012 ng Eq/ml, P less than 0.001). When human PTH(1-34) at a dose of 100 U was administered to these subjects, the mean increases in urinary excretions of adenosine cyclic 3',5'-monophosphate(cAMP) and inorganic phosphorus (Pi), expressed as increases in absolute amounts per unit time, were significantly lower in the elderly subjects. (3.65 +/- 1.02 vs 7.41 +/- 1.05 mumol/h, P less than 0.05 for cAMP and 14.7 +/- 6.3 vs 41.8 +/- 8.6 mg/2h, P less than 0.05 for Pi) and an inverse correlation was found between the serum PTH levels and the increases in urinary cAMP excretion (mumol/hr; r = -0.63, P less than 0.05). However, when corrected for the glomerular filtration rate (GFR) and the units of PTH administered per kg body weight, the increases were not significantly different in the two groups (elderly 52.1 +/- 7.5 vs young 60.0 +/- 19.2 nmol . kg/100 ml GFR . U . h for cAMP and 0.315 +/- 0.061 vs 0.186 +/- 0.044 mg . kg/100 ml GFR . U . 2 h respectively for Pi).(ABSTRACT TRUNCATED AT 250 WORDS)
Patients with chronic renal failure showed the existence of phosphate retention, secondary hyperparathyroidism, and reduced production of 1,25-(OH)2D. In order to determine the effect of correction of hyperphosphatemia on secondary hyperparathyroidism and vitamin D metabolism in those patients, 7 nondialyzed patients with chronic renal failure were treated with large doses of A1(OH)3 (15-18 g/day) to correct their high levels of serum phosphate. After treatment with A1(OH)3, serum phosphate fell significantly (p less than 0.005) from 6.3 +/- 1.3 (mean +/- SD) to 3.7 +/- 0.5 mg/dl. Serum parathyroid hormone decreased significantly (p less than 0.02) from 2.87 +/- 1.64 to 1.85 +/- 1.26 ngEq/ml. Serum 1,25-(OH)2D was low compared to the normal mean level before A1(OH)3 administration and decreased significantly (p greater than 0.02) from 19.4 +/- 6.1 to 11.4 +/- 4.3 pg/ml after the treatment. Aluminum levels increased significantly (p greater than 0.02) from 1.7 +/- 1.0 to 3.6 +/- 1.5 micrograms/dl. Serum calcium, calcitonin, and 25-(OH)D showed no significant change. Our data suggested that the suppression of secondary hyperparathyroidism by A1(OH)3 treatment results in a decrease of the 1,25-(OH)2D level in patients with chronic renal failure, even though their hyperphosphatemia has been corrected. We speculate that aluminum loading might play a role in diminishing the secretion of parathyroid hormone and the production of 1,25-(OH)2D in humans.