Yuichi Kumahara

An open study of vitamin D3 treatment in psoriasis vulgaris.

Active forms of vitamin D3, 1α‐hydroxyvitamin D3 and 1α, 25‐dihydroxyvitamin D3, were administered in an open‐design study to 40 patients with psoriasis vulgaris in three ways: (i)to 17 patients 1α, hydroxyvitamin D3 was given orally at a dose of 1.0μ/day for 6 months, (2) to four patients 1α, 25‐dihydroxyvitamin D3 was given orally at a dose of 0.5μ/day for 6 months, and (3)19 patients were given 1α, 25‐dihydroxyvitamin D3, was applied topically at a concentration of 0.5μ/g of base for 8 weeks. Improvement was observed at the end of the individual study periods in 13 (76%) patients in Group I 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.

The Seasonal Variation of Blood Pressure in Patients with Essential Hypertension

We examined the role of dietary electrolytes and humoral factors in causing seasonal changes in blood pressure. Normal subjects had no seasonal difference in blood pressure, although urinary sodium and norepinephrine were significantly higher in winter than in summer. In patients with essential hypertension blood pressure, urinary sodium and norepinephrine excretion and plasma norepinephrine concentration were significantly higher in winter. Plasma renin activity, plasma and urinary aldosterone and urinary kallikrein excretion were not significantly different between the two seasons in both normal subjects and hypertensive patients. In conclusions, the blood pressure of patients with essential hypertension has a seasonal variation with higher pressures in the winter than in the summer. Increased sympathetic nervous activity and an increased load of sodium presented to the kidney for excretion may be contributing factors in the rise in blood pressure in winter in patients with essential hypertension.

Correlation Between Minimal Secretory Capacity of Pancreatic β-Cells and Stability of Diabetic Control

The significance of the minimal secretory capacity of pancreatic β-cells for the stability of the plasma glucose level was studied in 20 patients with insulin-dependent diabetes mellitus. Changes in plasma concentrations of major counterregulatory hormones in response to hypoglycemia were also investigated in these patients to clarify their contribution to diabetic brittleness. β-Cell function was evaluated on the basis of elevation of plasma C-peptide immunoreactivity (CPR) during the intravenous glucagon test with a highly sensitive assay for plasma CPR that could detect as little as 0.03 ng/ml. After stimulation with glucagon, a significant increase in plasma CPR was observed in 10 of the patients whose β-cell function had been evaluated as completely depleted by a conventional assay for plasma CPR. A clear inverse correlation was found between the secretory capacity of pancreatic β-cells measured in this way and the degree of glycemic instability (r = −.74, P < .01). Infusion of insulin at a rate of 0.15 U.kg−1.h−1 for 60 min caused a continuous decrease in the plasma glucose level, resulting in neuroglycopenia in 7 of the 10 CPR nonresponders but only 2 of the CPR responders. During insulin-induced hypoglycemia, plasma glucagon immunoreactivity did not increase in the CPR nonresponders but increased significantly in the CPR responders. A positive correlation was found between the minimal residual β-cell capacity and the responsiveness of α-cells to hypoglycemia (r = .65, P < .01).In contrast to the difference in the responses of their pancreatic α-cells to hypoglycemia, the two groups showed more or less the same responses of plasma epinephrine, norepinephrine, growth hormone, and cortisol to hypoglycemia. Total lack of insulinogenic reserve inevitably results in loss of automatic regulation of the circulating insulin level and seems to be a major factor in causing hyperlability of diabetic control. The lack of β-cell function may be related causally to pancreatic α-cell dysfunction, which also contributes in part to metabolic variability in brittle diabetes.

Relation of doubling time of plasma calcitonin levels to prognosis and recurrence of medullary thyroid carcinoma.

Plasma calcitonin (CT) levels were measured serially in 54 patients surgically treated for medullary thyroid carcinoma. Patients with postoperative basal CT levels higher than 1 ng/ml measured within 1 month after surgery had a higher recurrence rate than those with lower CT levels (p < 0.002). Patients with postoperative basal CT levels higher than 2 ng/ml had a lower survival rate than those with lower CT levels (p < 0.01). However, pre-operative basal CT levels had no significant correlation with life expectancy or recurrence during the present observation period. Serial measurements in 23 patients with elevated postoperative CT levels showed exponential increases in basal CT levels in 19 patients (p < 0.05 in nine patients, 0.05 < p < 0.1 in four patients) and slight decreases in four (p < 0.05 in one patient). Doubling time of CT levels calculated from the regression line in each patient showed the highest correlation with 3-year survival, recurrence within 5 years, and time interval between surgery and clinical recurrence of the tumor, allowing quantitative prediction of the prognosis.

Genetic complementation groups in cockayne syndrome

Skin fibroblasts from patients with Cockayne syndrome (CS cells) exhibited marked ultraviolet (UV) sensitivity as measured by colony-forming ability. Further, recovery of semiconservative DNA synthesis following UV irradiation was absent in CS cells, as it is in xeroderma pigmentosum cells. We found that the rate of semiconservative DNA synthesis measured at 12 h after 12 J/m2 of UV irradiation had recovered to nearly normal levels in binuclear cells obtained by the fusion of CS strains CS3BE (GM1856) and CS7SE (GM1428) and of CS3BE (GM1856) and CS1BE (GM1629), but not of CS7SE (GM1428) and CS1BE (GM1629). These results indicate that there are at least two genetic complementation groups in CS.

Increased frequency of 6-thioguanine-resistant peripheral blood lymphocytes in Werner syndrome patients.

SummaryThe frequency of spontaneous 6-thioguanine (TG)-resistant peripheral blood lymphocytes in five unrelated Werner syndrome (WS) patients was determined using an autoradiographic labeling assay. The average frequency of TG-resistant lymphocytes was eightfold higher in WS patients than in sex- and age-matched normal control donors. This finding and previous identification of increased spontaneous chromosomal rearrangements and deletions in WS cells or cell lines suggest that WS is a human genomic instability or mutator syndrome.

Familial Isolated Thyrotropin Deficiency with Cretinism

Abstract Two sisters with nongoitrous cretinism, offspring of a consanguineous marriage, were found to have isolated thyrotropin (TSH) deficiency. Growth hormone, ACTH and gonadotropin secretion we...

The effect of oestrogens on human calcitonin secretion after calcium infusion in elderly female subjects.

The effect of oestrogen administration (4–6 weeks) on the response of human calcitonin (hCT) secretion to 5 min calcium infusions was studied in ten elderly women. There was no significant difference in mean basal plasma hCT levels before and after oestrogen administration. However, the mean increment in plasma hCT in response to calcium infusion (ΔhCT) increased significantly (P < 0·001) from 21·9±6·6 (mean ±SE) before treatment, to 79·6±15·5 ng/l after oestrogen administration. Mean serum calcium levels decreased significantly (P < 0·001) from 2·42 ±0·06 before to 2·19·0±07 mmol/l after oestrogen treatment. Mean plasma immunoreactive PTH (iPTH) levels increased significantly (P < 0·05) from 521·41 before to 696·96 ng/l after oestrogen treatment. To exclude out the possibility that the decreased serum calcium level itself might have influenced ΔhCT, 1α‐hydroxycholecalciferol (1α‐OH‐D3) was administered with oestrogens. While this resulted in a slight increase in serum calcium level, there was no significant difference in ΔhCT in response to calcium infusion following oestrogen treatment alone, and after combination therapy of oestrogen and 1 α‐OH‐D3. The primary action of administered oestrogen may be in stimulating hCT secretion which results in a decrease in plasma calcium concentration and an increase in plasma iPTH level.

Topical administration of 1,25-dihydroxyvitamin D 3 for proriasis: Report of five cases

SummaryThe effects of topical administration of 1,25-dihydroxyvitamin D3, as 0.1 and 0.5 μg per g base, and control base applied to contralateral skin lesions in five patients with persistant 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 μg 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.

Effects of prostaglandins on the cytosolic free calcium concentration in vascular smooth muscle cells.

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.