Kensuke Takatsuki

Aggravation of subclinical diabetes insipidus during pregnancy.

Abstract Background. Transient polyuria and polydip-sia during pregnancy are rare, and their cause is not en-tirely clear. Possible explanations include the exacerba-tion of preexisting abnormalities in the secretion or action of vasopressin and abnormally large increases in plasma vasopressinase activity. Methods. We studied two women in whom overt poly-uria and polydipsia developed during the third trimester of pregnancy and disappeared after delivery. The secretion and action of vasopressin were studied both when the women had polyuria and polydipsia and later, when their water intake and urine volume were normal. Results. One patient had partial nephrogenic diabetes insipidus. She had little increase in urine osmolality in re-sponse to water deprivation, hypertonic-saline infusion, and vasopressin injection and no response to desmopres-sin acetate (1-deamino-8-D-arginine vasopressin) during the immediate postpartum period. Her basal and stimulat-ed plasma vasopressin concentrations were high (16.5 to ...

Effect of the opioid kappa-receptor agonist U50488H on the secretion of arginine vasopressin. Study on the mechanism of U50488H-induced diuresis.

The effect of U50488H, a potent opioid kappa-receptor agonist, was investigated on the urine volume and on the secretion of arginine vasopressin (AVP) in response to dehydration or hyperosmolar or hypovolemic stimulation in conscious rats. This agonist markedly increased the urine volume in normally hydrated rats and suppressed plasma AVP in a dose-dependent manner in rats given hyperosmolar saline. This suppression of plasma AVP was completely reversed by concurrent injection of naloxone. U50488H also inhibited the release of AVP in dehydrated or hypovolemic rats. These findings indicate that the diuresis induced by U50488H is mainly caused by the suppression of plasma AVP. They also suggest that the kappa-opioid receptor plays an important role in regulating the secretion of AVP.

Association of HLA-DR Phenotypes and T-Lymphocyte–Receptor β-Chain–Region RFLP With IDDM in Japanese

Fifty Japanese patients with insulin-dependent diabetes mellitus (IDDM) and 94 normal subjects were genotyped for Bg/II restriction-fragment-length polymorphism (RFLP) of the T-lymphocyte-receptor β-chain (TLRβ)-region gene and analyzed in relation to HLA-DR phenotypes. The antigen frequencies of DR4 and DR9 in the IDDM population were significantly higher than those in the normal population, with relative risks of 1.87 (P < .02) and 2.42 (P < .01), respectively. Hybridization of digested DNA with the TLRβ probe revealed two alleles of 9.3 and 8.6 kilobases (kb). The allele frequency of 8.6 kb in patients with IDDM (79%) was significantly (P < .05) higher than that in normal subjects (64%). When TLRβ-region RFLP in IDDM was further analyzed with respect to the HLA-DR phenotypes, the frequency of 8.6 kb was significantly increased in patients with DR4 but not DR9 (DR4/X) and those with DR9 but not DR4 (DR9/X) compared with the frequency found in normal subjects (P < .05); the relative risks of 8.6 kb in DR4/X and DR9/X were 2.77 and 4.98, respectively. Although the frequencies of HLA-DR phenotypes and of TLRβ-region RFLP in IDDM and normal subjects were apparently different from those reported for Caucasians, this population-association study indicates that in the Japanese, genes conferring susceptibility to IDDM exist near or at the HLA-DR and the TLRβ loci, as has been demonstrated in Caucasians.

Effects of hypergravity on proliferation and differentiation of osteoblast-like cells

We investigated the effects of hypergravity on DNA synthesis and alkaline phosphatase (ALP) activity in cloned osteoblast-like cells, MC3T3-E1. Hypergravity (5 x g) stimulated DNA synthesis in these cells in a time-dependent manner and increased it approximately up to 150% of that of the control (1 x g). 12-O-Tetra-decanoylphorbol-13-acetate (TPA), a protein kinase C activator, and insulin-like growth factor I (IGF-I) enhanced DNA synthesis additively with hypergravity (5 x g). An increase in ALP activity induced by 10% fetal calf serum (FCS) was suppressed by hypergravity (2 x g, 5 x g). Five x g completely suppressed the increase in ALP activity. TPA and hypergravity (2 x g) suppressed the increase in ALP activity induced by FCS additively. Hypergravity (5 x g) showed no significant effect on cAMP nor cGMP production in these cells, but increased prostaglandin E2 (PGE2) production. Exogenous PGE2 stimulated DNA synthesis in these cells but had little effect on 10% FCS-induced ALP activity. These results suggest that hypergravity stimulates proliferation but suppresses differentiation of osteoblast-like cells through a pathway independent of the activation of protein kinase C and the production of cyclic nucleotides, and that hypergravity and IGF-I stimulate proliferation of these cells through an independent signal transduction pathway. Moreover, our data strongly suggest that PGE2 mediates the signalling of hypergravity on the proliferation of osteoblast-like cells.

Insulin-like growth factor-I stimulates45Ca-accumulation in cultures of osteoblast-like cells

SummaryThe effect of insulin-like growth factor-I (IGF-I) on calcification in cloned osteoblast-like MC3T3-E1 cells was studied by measuring accumulation of45Ca into sodium dodecyl sulfate-insoluble, EDTA-extractable structure that appeared after 2 weeks of culture. The accumulation of45Ca was markedly enhanced by incubating cells with IGF-I after 6 weeks of culture. The enhancement was dose-dependent in a range between 0.1 nM and 100 nM. IGF-I stimulated alkaline phosphatase activity in the cells cultured for 7 weeks dose-dependently between 0.1 nM and 100 nM. DNA synthesis examined in the cells cultured for 7 weeks was not influenced by 100 nM IGF-I. These results suggest that IGF-I stimulates Ca-accumulation in osteoblast-like cells without stimulating their proliferation.

Effect of Porcine Calcitonin in Primary Hyperparathyroidism

parathyroid adenoma. Fasting blood specimens were drawn at 8: 00 a.m. every other day and 24 hour urine samples were collected through out control and test days. To examine the acute effect of CT, blood and urine were checked several times until 8 hours after the first injection. A fall in the fasting serum calcium level observed in 5 patients during the repeated administrations of CT, as well as that observed in 6 patients within 6 hours after the first injection, showed a significant correlation with the initial serum calcium level. Serum

Aggravation of subclinical diabetes insipidus during pregnancy

BACKGROUND Transient polyuria and polydipsia during pregnancy are rare, and their cause is not entirely clear. Possible explanations include the exacerbation of preexisting abnormalities in the secretion or action of vasopressin and abnormally large increases in plasma vasopressinase activity. METHODS We studied two women in whom overt polyuria and polydipsia developed during the third trimester of pregnancy and disappeared after delivery. The secretion and action of vasopressin were studied both when the women had polyuria and polydipsia and later, when their water intake and urine volume were normal. RESULTS One patient had partial nephrogenic diabetes insipidus. She had little increase in urine osmolality in response to water deprivation, hypertonic-saline infusion, and vasopressin injection and no response to desmopressin acetate (1-deamino-8-D-arginine vasopressin) during the immediate postpartum period. Her basal and stimulated plasma vasopressin concentrations were high (16.5 to 203.4 pmol per liter) before and during hypertonic-saline infusion 30 months post partum. The other patient had partial neurogenic diabetes insipidus. She had subnormal basal plasma vasopressin concentrations, a subnormal increase in the plasma vasopressin level and a subnormal decrease in urine flow in response to the administration of vasopressin, and a normal response to desmopressin. After pregnancy, when her urine volume was normal, she had no increase in plasma vasopressin in response to hypertonic-saline infusion, but she had a normal rise in the plasma vasopressin level and a normal renal response to vasopressin administration. CONCLUSIONS Pregnancy may unmask subclinical forms of both nephrogenic and neurogenic diabetes insipidus. This exacerbation may result from both increased vasopressinase activity and diminished renal responsiveness to vasopressin.

Development of Simple and Sensitive System for Detection of Bone Seeking Substances Employing Chick Embryo Tibiae

Hypercalcemia is one of the most common complications of malignant diseases. Besides metastatic bone lesions, systemic bone resorption mediated by humoral factors which are produced by tumors causes hypercalcemia. Among many factors attributed to the “humoral hypercalcemia of malignancy”, the adenylate cyclase stimulating factor (ACSF), first described by Stewert et al. (1) in 1980, has been most extensively studied. Recently an ACSF isolated from a lung carcinoma was purified by Martin et al. (2). It is a polypeptide of 18,000 daltons having a remarkable homology with human parathyroid hormone (hPTH). However, ACSFs with different molecular weight have been reported by other investigators, suggesting that there may be multiple ACSF species.

Determination of enolase isozymes in various adrenal gland tumours

Enolase isozymes (α enolase and γ enolase) in the extracts of adrenal tumours (phaeochromocytoma, adenoma of primary aldosteronism and Cushings syndrome, and neurinoma) were determined by means of enzyme immunoassay systems. The mean ± SEM, respectively, of α and γ enolase levels were 2.5 ± 0.37 μg/mg protein and 3‐2 ± 0–69 μg/mg protein for 9 phaeochromocytomas, 15.2 + 3.1 μg/mg protein and 0.65 ± 0.18 μg/mg protein for three adenomas with primary aldosteronism, 10.8 ± 3.0 μg/mg protein and 0.23 ± 0.02 μg/mg protein for five adenomas causing Cushings syndrome, and 3.8 ± 0.88 μg/mg protein and 0.30 ± 0.15 μg/mg protein for three neurinomas. Thus, the γ enolase concentration in the extract of phaeochromocytoma was higher than that of other adrenal tumours. The serum level of γ enolase was determined in 36 patients with adrenal tumours and 26 normal controls by radioimmunoassay. The mean + SEM of γ enolase level was 5.4 ± 0.3 ng/ml in normal controls, 91 ± 0.9 ng/ml for 10 patients with phaeochromocytoma, 6.3 ± 0.3 ng/ml for 11 with primary aldosteronism, 5.5 ± 0.4 ng/ml for 11 with Cushings syndrome, and 5.1 ± 0.7 ng/ml for four with neurinoma. Thus, patients with phaeochromocytoma had a significantly higher serum γ enolase levels than did those with tumours derived from adrenal cortex and normal controls. In patients with phaeochromocytoma, serum γ enolase levels showed a significant positive correlation with urinary adrenaline levels (P<0.05), and after resection the elevated level of γ enolase fell significantly (P<0.05) and returned to normal. These results indicate that γ enolase in serum may be a useful marker for the differential diagnosis of adrenal tumours and therapeutic monitoring of phaeochromocytoma.