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Biomedical subjects

M Fukase

Publications and source records attributed to M Fukase.

At least 145 records · Page 8Linked to original sources
PubMed1986

Degrading activity for human parathyroid hormone [PTH-(1-84)] in rat osteoblast-like osteosarcoma cell line UMR106.

The degrading activity for human parathyroid hormone [hPTH-(1-84)] was studied in a rat osteoblast-like osteosarcoma cell line UMR106. At 37 C,UMR106 cells degraded hPTH-(1-84) into fragments in a time-dependent manner, which was shown by a radioimmunoassay with the use of antibody recognizing the C-terminal and middle regions of PTH molecule, whereas the degradation was completely suppressed at 4 C and failed to occur in the absence of the cells. The Lineweaver-Burk plot of this degrading activity at 37 C showed a fairly good linearity and gave a Km value of 5.1 X 10(-7) M. Reverse-phase high-performance liquid chromatography (HPLC) analysis of immunoreactive PTH fragments in the medium disclosed two peaks aside from intact PTH, indicating a limited PTH-hydrolyzing activity of UMR106 cells cleaving the molecule between at least two separate positions. This study suggests the possible involvement of osteoblasts on the metabolism of intact PTH.

Animals↗
PubMed1986

Phorbol esters stimulate phosphate accumulation synergistically with A23187 in cultured renal tubular cells.

The effects of phorbol esters and diacylglycerol on phosphate accumulation in the cultured mouse kidney cells were investigated to assess the possible role of Ca2+-activated, phospholipid dependent protein kinase (protein kinase C) on the renal phosphate handling. 12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulated phosphate accumulation dose-dependently. TPA-induced phosphate accumulation was synergistically enhanced with A23187. 4 alpha-phorbol 12,13-didecanoate did not stimulate the phosphate accumulation, while 4 beta-phorbol 12,13-didecanoate stimulated it. Additionally, 1-oleoyl-2-acetyl-glycerol exhibited a stimulatory effect on phosphate accumulation. These data indicated that protein kinase C is one of possible regulators of phosphate transport at the renal tubules.

Animals↗
PubMed1986

Characteristics of parathyroid hormone-specific cyclic changes of glucose-6-phosphate dehydrogenase activity in the distal convoluted tubule of the guinea pig.

The effect of parathyroid hormone (PTH) on the time course of glucose-6-phosphate dehydrogenase (G6PD) activity in the distal convoluted tubule of a vitamin D-depleted guinea pig was determined using quantitative cytochemistry. G6PD activity decreased to the stable basal level 5 hrs after the initiation of the kidney segment maintenance cultures. The exposure of the tissues to 1 pg/ml of bovine PTH-(1-84) induced a cyclic change of G6PD activity, whereas neither carboxyl-terminal PTH nor other hormones tested showed such activity. After a 16-min exposure to bovine PTH-(1-84), the peak height of each cycle began to decrease until it disappeared at 34 min. The second exposure to this hormone at 46 min reinduced a similar cyclic change with a similar peak, indicating full viability of the cells. When bovine PTH-(1-84) was incubated with an excess amount of anti-bovine PTH antibody, the PTH-induced G6PD activity was completely abolished. Throughout a 14-min exposure to either human PTH-(1-84), human PTH-(1-34) or bovine PTH-(1-84), similar cyclic changes were observed with the constant peak height regardless of the dose (10(-16)-10(-12) M), although the cycle length shortened progressively as the dose was increased. They were equipotent on a molar basis between the concentrations of 10(-16) and 10(-13) M at 6 min of hormone exposure. The present data demonstrate that the cytochemical bioassay of PTH in a vitamin D-depleted animal is based on a dose-dependent difference in the time course of G6PD activity.

Animals↗
PubMed1986

Effects of ascorbic acid on alkaline phosphatase activity and hormone responsiveness in the osteoblastic osteosarcoma cell line UMR-106.

L-ascorbic acid at physiological concentrations (10 micrograms/ml) increased alkaline phosphatase activity in the osteoblastlike rat osteosarcoma cell line, UMR-106. The increase was dose-dependent and detectable at 6 hours after the addition of 100 micrograms/ml ascorbic acid to the medium. Treatment of the cells with 100 micrograms/ml ascorbic acid potentiated the response of cAMP to both PTH and PGE1, while cell growth was inhibited. Furthermore, the number of colonies formed by the cells grown in the soft agar was significantly reduced by increasing concentrations of ascorbic acid. These results indicate that ascorbic acid might play some role in the differentiation of osteoblasts.

Alkaline Phosphatase↗
PubMed1986

Altered parathyroid hormone- or calcitonin-stimulated adenosine 3', 5'-monophosphate release by isolated perfused bone from glucocorticoid-treated rats.

The present studies were designed to examine in vivo effects of glucocorticoid on PTH-or calcitonin (CT)-stimulated adenosine 3',5'-monophosphate (cAMP) release from the isolated perfused bone of rat and to test whether the duration of glucocorticoid administration influenced such effects. We assessed the ability of acute (24 hour) or chronic (2 week) dexamethasone administration to modulate the cAMP response to 5 micrograms human PTH-(1-34) or 1 micrograms eel CT. Acute treatment with dexamethasone (1 mg/100 g body wt) increased the cAMP response to PTH, but decreased the response to CT. This enhanced effect on PTH-stimulated cAMP release was not apparent in the presence of phosphodiesterase inhibitor 3-isobutyl-1-methyl-xanthine (IBMX, ImM). In contrast, chronic dexamethasone treatment (0.2 mg daily for 2 weeks) led to a decrease in both PTH- and CT-stimulated cAMP release. Such impaired response of the dexamethasone-treated bones to PTH was also found in rats that underwent parathyroidectomy 24 hours before sacrifice. These data indicate that 1) the duration of glucocorticoid administration may influence the effect of PTH on bone and 2) glucocorticoid may decrease cAMP-mediated CT function, regardless of the duration of treatment.

1-Methyl-3-isobutylxanthine↗
PubMed1986

Impaired parathyroid hormone-stimulated adenosine 3',5'-monophosphate release by isolated perfused bones obtained from vitamin D-deficient rats.

The present studies were designed to explore the mechanism underlying skeletal refractoriness to PTH in a vitamin D-deficient animal by assessment of PTH-stimulated cAMP release from isolated perfused bone. In vitamin D-deficient (-D) rats both basal and PTH-stimulated cAMP release were markedly diminished, compared with that in vitamin D-replete (+D) rats. Isolated perfused bones from -D rats that had undergone parathyroidectomy 2 days before death still showed reduced cAMP release in response to PTH, compared with +D bones. To investigate which factors in terms of Ca, endogenous PTH, or vitamin D might primarily be responsible for the impaired PTH-stimulated cAMP release from -D bones, some -D rats were switched to a diet identical to the vitamin D-deficient diet but with high Ca content (4%) for 2 or 5 weeks before death. This schedule maintained normocalcemia despite vitamin D deficiency. PTH-stimulated cAMP release in these rats was increased to a level intermediate between that in -D rats and +D rats, indicating partial restoration of the impaired response to PTH in -D rats. These data indicate that skeletal refractoriness to PTH in vitamin D-deficient animals might, in part, be due to the impaired activation of adenylate cyclase, which cannot be explained entirely by hypocalcemia or associated secondary hyperparathyroidism. Vitamin D deficiency per se, therefore, may play a key role in the impaired cAMP response to PTH.

Animals↗
PubMed1986

Calcitonin gene-related peptide stimulates somatostatin release from isolated perfused rat stomach.

Effect of calcitonin gene-related peptide (CGRP) on somatostatin release was investigated on the isolated perfused rat stomach. Perfusion with CGRP (0.1 nM-100 nM) caused a significant and dose-dependent increase in effluent somatostatin levels. The somatostatin response to CGRP was rapid in onset and reversible immediately after the cessation of CGRP infusion. These findings suggest that CGRP stimulates the release of gastric somatostatin, thereby modulating gastric functions in rat.

Animals↗
PubMed1986

Establishment of a parathyroid hormone-responsive phosphate transport system in vitro using cultured renal cells.

A new system was established using primary cultured mouse kidney epithelial cells to study the effect of PTH on renal tubular phosphate transport. The cells used in our study had alkaline phosphatase activity. They showed increased cAMP content in response to PTH, calcitonin, and vasopressin. Thus, these cells were thought to be a mixture of cells originating from the proximal and distal renal tubules. To explore the mechanism of phosphate handling in these cells, the accumulation of radioactive phosphate from the medium into the cells and the spaces between the cell layer and culture plate (submonolayer spaces) was measured. The accumulation of phosphate by the cells was a sodium-dependent, energy-dependent process, which was demonstrated by inhibition both in the absence of sodium and in the presence of ouabain or 2,4-dinitrophenol. Furthermore, phosphate accumulation was decreased significantly by PTH presumably acting through cAMP. PTH inhibited phosphate accumulation not by affecting the efflux process, but by affecting the uptake process through the apical membrane of the cultured cells without altering the compartmental mental distribution of the accumulated phosphate. These characteristics of phosphate accumulation resemble those of renal tubular phosphate transport.

2,4-Dinitrophenol↗
PubMed1986

Identification of parathyroid hormone messenger ribonucleic acid in an apparently nonfunctioning parathyroid carcinoma transformed from a parathyroid carcinoma with hyperparathyroidism.

mRNA coding for pre-pro-PTH, a precursor of PTH, was sought in an apparently nonfunctioning parathyroid carcinoma that had transformed from one that was previously functioning. Total poly(A+) RNA was prepared by phenol-chloroform-isoamyl alcohol extraction and oligo-dT-cellulose affinity chromatography from the tumor tissue and bovine parathyroid glands. In the rabbit reticulocyte lysate cell-free translation system, total poly(A+) RNA from the tumor as well as that from bovine parathyroid glands directed the translation of a product which was specifically precipitated by an anti-PTH serum and which migrated at the same position as pre-pro-PTH on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. These results indicated the presence of mRNA coding for pre-pro-PTH (PTH mRNA) in an apparently nonfunctioning parathyroid carcinoma, suggesting that PTH synthesis is not always absent in parathyroid carcinomas which are not accompanied by hyperparathyroidism.

Animals↗
PubMed1986

Effect of ipriflavone on bone changes induced by calcium restricted, vitamin D deficient diet in rats.

The preventive effect of ipriflavone, 7-isopropoxy-isoflavone, on the development of experimental osteopenia in rats was studied. Male Wistar rats (4 weeks old) on a calcium restricted, vitamin D deficient diet were given a daily oral administration of ipriflavone. The administration of ipriflavone (100 mg/kg BW/day) for 40 days significantly inhibited a decrease in the cortical thickness (14.0 +/- 1.6 vs. 17.1 +/- 2.9%, mean +/- SD, p less than 0.05) and bone calcium content (62 +/- 4 vs. 67 +/- 2 mg, p less than 0.05) in the femora of rats induced by a mild calcium restricted (0.3%), vitamin D deficient diet. This compound did not affect serum calcium levels in this condition. But a dose of 20 mg/kg BW/day of ipriflavone was insufficient to inhibit a decrease in bone calcium content. In rats fed on a more severe calcium restricted (0.03%), vitamin D deficient diet, the administration of ipriflavone (100 mg/kg BW/day) did not significantly affect the cortical thickness or calcium content. Intestinal calcium absorption measured by the in situ loop method was not significantly different between rats fed with a severe calcium restricted (0.03%), D deficient diet with or without ipriflavone (20 or 100 mg/kg BW/day) These results demonstrate that the new compound, ipriflavone, partially prevents bone calcium loss induced by a mild calcium restricted (0.3%), vitamin D deficient diet in rats. However, the precise mechanism of action of this compound remains unknown.

Animals↗
PubMed1986

Effect of aldosterone on dome formation by MDCK mono-layer.

Effect of aldosterone on the dome formation in the reconstructed MDCK cell epithelia was studied. MDCK cells derived from dog kidney are assumed to be originated from distal tubules or collecting ducts. When cultured to a confluency, these cells formed a epithelial layer with many domes which contained fluid transported from the apical to the basolateral surface through this layer. Aldosterone at a concentration of 10(-8) to 10(-6) M increased the number of domes dose-dependently, probably through a receptor mediated process, since the dome formation induced by this hormone was completely abolished in the presence of spironolactone. This study primarily disclosed that the dome formation in MDCK cells was stimulated by aldosterone, probably through a receptor mediated mechanism.

Aldosterone↗
PubMed1986

Effect of 1 alpha (OH)-vitamin D3 on insulin secretion in diabetes mellitus.

Fourteen non-insulin-dependent diabetic subjects were placed on a balanced diet for 2-3 weeks followed by the same balanced diet alone (group I: control, n = 7) or daily administration of 1 alpha (OH)-vitamin D3 (1 alpha (OH)D3) (group II: 2 micrograms/day, n = 7) additionally for the next 3 weeks. A 75 g oral glucose loading test was conducted before and after the experiment and the plasma insulin response was compared along with the metabolic parameters including serum calcium, phosphorus and serum lipids. The following results were obtained. (1) Total insulin secretion in response to 75 g glucose loading was significantly increased in group II (16.3 +/- 3.9 microU/2 h/ml versus 22.7 +/- 4.9 microU/2 h/ml; P less than 0.05), though no difference was demonstrated in group I. (2) Mean serum calcium level was significantly increased from 9.4 +/- 0.1 mg/dl to 9.6 +/- 0.1 mg/dl (P less than 0.05) and serum free fatty acid level was decreased from 0.80 +/- 0.07 mEq/l to 0.53 +/- 0.07 mEq/l (P less than 0.05) in group II, but not in group I. (3) However, there was no direct correlation between total insulin secretion during a 75 g oral glucose loading test and serum calcium or free fatty acid level. The findings that 1 alpha (OH)D3 enhances insulin secretion and reduces the levels of serum free fatty acid in non-insulin-dependent diabetics provide us with the possibility that vitamin D may play some role in the regulation of insulin secretion.

Adult↗
PubMed1985

12-O-tetradecanoyl phorbol-13-acetate (TPA) stimulates somatostatin release from isolated perfused rat stomach.

Effect of TPA (12-O-tetradecanoyl phorbol-13-acetate), a potent tumor promoter, on immunoreactive somatostatin release was investigated using the isolated perfused rat stomach. TPA at the concentration as low as 20nM significantly stimulated the somatostatin release from isolated perfused rat stomach. The integrated net output of somatostatin induced by TPA was dose-dependent in a range of 5 - 50nM TPA. Since TPA is known to activate C-kinase specifically at a low dose (less than 20nM), these findings suggest that C-kinase system may be involved in the regulation of somatostatin release in rat stomach.

Animals↗
PubMed1985

Phorbol ester stimulates calcitonin secretion synergistically with A23187, and additively with dibutyryl cyclic AMP in a rat C-cell line.

The mechanism of action of 12-O-tetradecanoyl phorbol-13-acetate (TPA) on calcitonin secretion was studied in a rat C-cell line, rMTC 6-23. TPA stimulated calcitonin secretion at the concentration of 16nM. This effect was synergistically enhanced with calcium ionophore, A23187. Synthetic diacylglycerol, 1-oleoyl-2-acetyl-glycerol (OAG), also showed a synergism with A23187 on calcitonin secretion. When dibutyryl cyclic AMP was added with TPA, an additive effect was obtained. These data suggest that C-kinase might be a possible regulator of calcitonin secretion in addition to the cyclic AMP-mediated pathway.

Animals↗
PubMed1985

Effect of calcium channel agonist Bay K 8644 on calcitonin secretion from a rat C-cell line.

Bay K 8644, a novel dihydropyridine, stimulates calcitonin secretion in a dose-dependent manner from a rat medullary thyroid carcinoma cell line, rMTC 6-23, and causes an increase in cytosolic free calcium concentration, as measured by quin-2. These effects are competitively inhibited by nifedipine, and completely abolished in the absence of extracellular calcium. These data suggest that calcium influx via voltage-dependent calcium channels plays a crucial role in the regulation of cytosolic free calcium concentration and calcitonin secretion.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1985

Significance of preoperative use of ultrasonography in parathyroid neoplasms: comparison of sonographic textures with histologic findings.

The sonographic textures of 10 parathyroid tumors in nine patients were examined and compared with their histologic features, particularly with the amount of fibrous trabeculae. The carcinomas containing a large amount of fibrous trabeculae, which is the most frequent finding in parathyroid cancer, were very echogenic. On the other hand, the adenomas without fibrous trabeculae showed a low echogenicity. These data suggest that the possibility of malignancy is high when the parathyroid tumor is found to be very echogenic.

Adenoma↗
PubMed1985

Cystinosis with marked atrophy of the kidneys and thyroid. Histological and ultrastructural studies in an autopsy case.

The eldest autopsied case (a 23-year-old man) of infantile form of cystinosis with uremia and myxoedema was reported. The cystine content per gram wet tissue of various organs was arranged as follows: the thyroid (4.61 mg), kidney (1.71 mg), eye (0.75 mg), spleen (0.65 mg), liver (0.49 mg), and brain (0.016 mg). In polarized light microscopy, cystine crystals were detected in the epithelial cells and epithelial lumina of both kidneys by Wollaston test, and foam cells with cystine crystals were histologically found in the reticuloendothelial and other organs, especially in the bone marrows. Moreover, electron microscopic findings revealed square, rectangular or lozenge-shaped small cystine crystal profiles in osmophilic dense bodies of the histiocytic cells and in the cytoplasm of the foam cells. In some of them, positive reaction for acid phosphatase activity was specifically localized at the periphery of the cystine crystal profiles.

Adult↗