Biomedical subjects

M Fukase

Publications and source records attributed to M Fukase.

At least 91 records · Page 5Linked to original sources

PubMed1991

Role of increase in intracellular calcium in PTH-induced homologous desensitization in UMR-106 cells.

Effects of increase in intracellular calcium on PTH-induced homologous desensitization were investigated using calcium ionophores. Pretreatment of UMR-106 cells (rat osteoblast like osteosarcoma cell line) with calcium ionophores (A23187 or ionomycin) for 6h resulted in approximately 50% decrease of PTH-stimulated cAMP production. PTH receptor binding, assessed with 125I-[Nle8,Nle18,Tyr34]PTH-(1-34) as radioligand, was significantly decreased in 10(-6) M calcium ionophore-pretreated (for 6h) cells without affecting the dissociation constant (Kd) for PTH. Minimal effective treatment period was 2h and similar inhibitory effect was observed in 12h-treated cells. These data suggest that increase in intracellular calcium might also act on PTH receptor in the similar manner as protein kinase C activation to induce desensitization.

Animals↗

PubMed1991

Phorbol ester induces desensitization of PTH-stimulated cyclic AMP production by decreasing the PTH receptor binding in UMR-106 cells.

Pretreatment of UMR-106 cells (rat osteoblast like osteosarcoma cell line) with the protein kinase C(PK-C) activating phorbol ester, phorbol 12-myristate 13-acetate (PMA) results in a time dependent (1-12h) desensitization of PTH-stimulated cAMP production. Compared to controls, PMA-treated cells showed 50% decrease of PTH-stimulated cAMP production. PK-C inhibitor, H-7 significantly blocked this PMA-induced desensitization. PTH receptor binding, assessed with 125I-[Nle8,Nle18,Tyr34]PTH-(1-34) as radioligand, was decreased by about 20% in PMA-treated cells. H-7 treatment completely restored receptor binding in PMA-treated cells. These data suggest that PK-C might act directly on PTH receptor which is coupling to adenylate cyclase, and induce desensitization.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1991

Platelet-derived growth factor B chain homodimer enhances chemotaxis and DNA synthesis in normal osteoblast-like cells (MC3T3-E1).

We demonstrate that recombinant platelet-derived growth factor B chain homodimer (PDGF-BB) could induce both the chemotactic activity and the DNA synthesis in a normal osteoblast-like cell line (MC3T3-E1). Cell migration toward recombinant human PDGF-BB was observed with the modified Boyden chamber technique. Maximum chemotaxis was exhibited at 25 ng/ml of PDGF-BB. DNA synthesis as indicated by [3H]-thymidine incorporation was also enhanced about 4-fold at 25-100 ng/ml PDGF-BB. Our results suggested that PDGF might be one of the candidates among local coupling factors for bone remodeling.

Animals↗

PubMed1991

Immunohistologic evaluation of parathyroid hormone-related protein in human lung cancer and normal tissue with newly developed monoclonal antibody.

With a newly developed monoclonal anti-PTHrP antibody, 4B3, the immunohistochemical localization of the parathyroid hormone-related protein (PTHrP) was studied on the formalin-fixed and paraffin-embedded sections of normal human tissues and various subtypes of lung cancer. Among normal epithelial tissues, keratinocytes in squamous epithelia, transitional and bronchial epithelia with squamous metaplasia, meningoepithelial cells, and mammary ductal cells with lactating changes showed positive immunoreactivity. Also, among endocrine tissues, cells in the parathyroid gland, pancreatic islets, adrenal cortex, pituitary gland, and testis were sporadically positive for PTHrP. These distribution patterns suggested that in a physiologic condition, PTHrP was closely related to keratinization and local secretion and/or the metabolism of calcium in specifically differentiated tissues. In lung cancer, however, PTHrP was detected in all cases of well-differentiated and moderately differentiated squamous cell carcinoma and in most cases of small cell carcinoma, irrespective of the patients' serum calcium level. However, PTHrP was not detected in two of five cases of poorly differentiated squamous cell carcinoma and in all cases of adenocarcinoma. Consequently, it was found that PTHrP was commonly produced by squamous cell carcinomas of the differentiated type, and that humoral hypercalcemia of malignancy could be induced when the PTHrP transgressed the homeostatic mechanisms.

Adenocarcinoma↗

PubMed1991

Correlates of cortical bone mass among premenopausal and postmenopausal Japanese women.

Few studies have examined the multifactorial risk factors of bone mass in Asian populations. This cross-sectional study was designed to explore relationships between bone mass and environmental variables, including dietary and life-style factors, in Japanese women living in Japan. A total of 178 Japanese women completed the study: 89 premenopausal, ages 35-40, and 89 postmenopausal, ages 55-60. Midradial bone mineral content (MBMC) and bone mineral content per unit area, referred to as bone density (MBMD), were measured using single-photon absorptiometry. The major results of this investigation were the following: (1) The postmenopausal women differed significantly from the premenopausal women in having lower radial bone parameters, lower mean height, later age of menarche, and higher dietary intakes of carbohydrates, vegetables, and milk with a lower intake of caffeine. (2) Current protein intake was a positive correlate of MBMC in both groups. (3) Intake of vegetables (leafy green, yellow, orange, and white) and current milk intake were positively associated with MBMC in the postmenopausal women. (4) For the premenopausal women, irregular menstrual cycles was a negative correlate of MBMC, and for the postmenopausal women, years of menopause was negatively associated with MBMC and MBMD. Longitudinal studies are needed to establish more conclusively associations among diet, life-style, and reproductive history and bone mass of Japanese women.

Adult↗

PubMed1991

Bone histomorphometric analysis for the cause of osteopenia in vitamin C-deficient rat (ODS rat).

A particular strain of rat, the osteogenic disorder rat (ODS rat), was established in 1973. Phenotypic expression of od/od in ODS rat develops signs characteristics of a vitamin C-deficient animal, with bleeding tendencies and limb fractures. We investigated the bone histomorphometry to clarify the pathogenesis of osteopathy found in ODS rat. Bone histomorphometry revealed that static parameters reflecting bone formation were found to be remarkably decreased in od/od rats. These observations were more prominent in the metaphysis of distal femurs of od/od rats than those in the tail vertebrae. Parameters reflecting bone resorption in od/od rats were reduced in the distal femoral metaphysis, but were similar to those of controls in the tail vertebrae. These parameters were restored to control levels after ascorbic acid supplementation to pair-fed od/od rats. The mineral appositional rate in od/od rats was not significantly different from that in controls. Although body weight gain in pair-fed controls was significantly reduced compared to those fed ad libitum, histomorphometric parameters, on the contrary, were unaltered between these groups. Our present study provides evidence that the cause of osteopenia found in od/od rat is attributable to an imbalance between the total amounts of resorption and formation, and the pathogenesis of osteopathy could be due to ascorbic acid deficiency itself rather than malnutrition.

Alkaline Phosphatase↗

PubMed1991

Two cases of gastric antral vascular ectasia--response to medical treatment.

Two patients with severe iron deficiency anemia and gastric antral vascular ectasia (GAVE) are reported. The anemia caused by the chronic blood loss from the abnormally dilated mucosal and submucosal capillary veins in the gastric antrum was unresponsive to oral iron supplementation. However, one of the patients was successfully treated with intramuscular injection of (Asu1,7) eel calcitonin. The other one was treated by oral prednisolone with resulting improvement iron deficiency anemia. The possible mechanisms of successful calcitonin and prednisolone treatments on chronic blood loss from GAVE is discussed.

Aged↗

PubMed1991

Effects of continuous infusion of parathyroid hormone and parathyroid hormone-related peptide on rat bone in vivo: comparative study by histomorphometry.

We have investigated the actions of parathyroid hormone (PTH) and PTH-related peptide (PTHrP) on the bones of parathyroidectomized (PTX) rats by histomorphometric analysis. Miniosmotic pumps filled with either human PTH (hPTH)(1-34), hPTHrP(1-34) or vehicle were subcutaneously implanted on the backs of the rats. The peptides were continuously infused for 6 days at a rate of 15 nmole/kg/day. PTH and PTHrP exhibited similar hypercalcemic and hypophosphatemic actions on these PTX rats. No significant differences were noted in bone weight or calcium and phosphorus contents of the ashed bone among the 3 groups. By quantitative histomorphometric analysis, hPTH(1-34) and hPTHrP(1-34) were found similarly to enhance both bone formation and resorption. Peritrabecular fibrosis was observed only in the PTH-infused animals. PTHrP thus mimics the actions of PTH, but is not as effective in promoting mesenchymal cell proliferation along the bone trabeculae.

Animals↗

PubMed1991

Calcium treatment of essential hypertension in elderly patients evaluated by 24 H monitoring.

We used 24-h monitoring of blood pressure (BP) to evaluate the effect of calcium supplementation on mild to moderate essential hypertension in elderly hospitalized patients for the first time in a controlled crossover study. The mean systolic and diastolic BP over a period of 24 h declined by 13.6 mm Hg (P less than .005) and 5.0 mm Hg (P less than .05) respectively in patients whose diet was supplemented with 1 g of elemental calcium in the form of oystershell electrolysate (AA calcium). Serum ionized calcium and urinary calcium and sodium excretion increased (serum Ca2+ 0.16 +/- 0.03 mEq/L, P less than .05; FECa 0.5 +/- 0.2%, P less than .05; FENa 0.4 +/- 0.1%, P less than .05) and plasma parathyroid hormone was suppressed (12.2 +/- 2.3 pg/mL, P less than .005). These data suggest that supplementation of dietary calcium may contribute to a reduction of BP in elderly patients with essential hypertension.

Aged↗

PubMed1991

Role of endogenous endothelin in the development of hypertension in rats.

To further elucidate the pathophysiologic role of endogenous endothelin (ET), we have studied the chronic effect of anti-ET gamma-globulin on the development of hypertension in spontaneously hypertensive rats (SHR) and stroke prone SHR (SHR-SP) for three weeks. In neither SHR nor SHR-SP did repetitive bolus injection of anti-ET gamma-globulin suppress the rise in blood pressure. The present data suggest that endogenous ET is not likely to play a key role in the development of hypertension, although ET may induce a local vasoconstriction at the injured vascular wall.

Animals↗

PubMed1991

Protein kinase C is involved in PTH-induced homologous desensitization by directly affecting PTH receptor in the osteoblastic osteosarcoma cells.

We have investigated mechanisms of PTH-induced homologous desensitization reflected in the refractoriness of cAMP response to the second exposure to PTH in the clonal rat osteosarcoma cell line, UMR-106. Preincubation with 10(-7) M rat (r) PTH-(1-34) for 6 h caused the desensitization, resulting in a 65% decrease in cAMP accumulation in response to further exposure to rPTH. This desensitization was apparent at 10(-10) M rPTH and maximal at 10(-7) M rPTH. UMR-106 cells treated with protein kinase C (PK-C) activating phorbol ester, phorbol 12-myristate 13-acetate (PMA, 10(-6) M) for 6 h also induced desensitization manifested by a loss of rPTH-stimulated cAMP accumulation to 50% of that in the control cells. On the other hand, 4 alpha-phorbol 12,13-didecanoate, incapable of activating PK-C, failed to induce desensitization. Fifty micromolar H-7 (PK-C inhibitor) significantly blocked both rPTH- and PMA-induced desensitization. Thus, PK-C seemed to play a major role in rPTH-induced desensitization. Pretreatment with neither rPTH nor PMA changed the cAMP responsiveness to 10 micrograms/ml cholera toxin or 100 microM forskolin. Islet activating protein failed to influence the desensitization in this cell line. PTH receptor binding, assessed by using 125I-labeled [Nle8,Nle18,Tyr34]PTH-(1-34) as a radioligand, was decreased along with PTH receptor numbers by pretreatment with rPTH or PMA. These data indicate that rPTH-induced homologous desensitization occurs at least in part through the activation of PK-C and that PK-C directly affects PTH receptor in UMR-106 cells.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1991

[Immunohistochemical study of parathyroid hormone related protein (PTHrP) in renal cell carcinoma].

Parathyroid hormone related protein (PTHrP) is the main factor of humoral hypercalcemia of malignancy (HHM). Using anti-PTHrP monoclonal antibody 4B3, we investigated the immunohistochemical localization of PTHrP in human normal renal tissues and renal cell carcinomas. Among normal renal tissues, distal tubules and collecting ducts showed positive immunostaining. Among 36 cases of renal cell carcinoma, PTHrP was detected in 30 cases (83%), and there was no significant correlation between the degree of the immunostaining and the serum calcium levels of the patients. As for the histopathological types of the renal cell carcinomas, granular cell subtypes tended to be more strongly positive than clear cell ones. In conclusion, it was not uncommon that PTHrP was commonly presented by renal cell carcinoma, and HHM occurred when the PTHrP transgressed the homeostatic mechanisms.

Adult↗

PubMed1990

The effect of 1,25-dihydroxyvitamin D3 on human osteoblast-like osteosarcoma cell: modification of response to PTH.

The influence of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] on adenylate cyclase responsiveness in cultured osteoblastic cells was studied using a human osteosarcoma cell line SaOS-2. 1,25(OH)2D3 treatment had no effect on cell growth, cell protein and alkaline phosphatase activity. 1,25(OH)2D3 did not alter the basal production of cyclic AMP (cAMP) in intact cells, but the cAMP formation in response to parathyroid hormone (PTH), isoproterenol (ISO) and cholera toxin was attenuated by 1,25(OH)2D3. The response to forskolin, however, was unaffected by 1,25(OH)2D3 treatment. Islet activating protein failed to modify these 1,25(OH)2D3 effect. In cell free experiments, 1,25(OH)2D3 showed similar effect--that is, PTH and ISO-stimulated adenylate cyclase activity were attenuated, but forskolin-stimulated adenylate cyclase was unaffected. 1,25(OH)2D3 treatment had no effect on the kinetics of PTH binding to PTH receptor and on the ADP ribosylation of GTP stimulatory binding protein (Gs) in SaOS-2 cells. According to these results, 1,25(OH)2D3 appeared to change the coupling of Gs with adenylate cyclase, but does not affect receptor, Gs and adenylate cyclase themselves, nor GTP inhibitory binding protein.

Adenylyl Cyclases↗

PubMed1990

Autocrine effect of endothelin on DNA synthesis in human vascular endothelial cells.

To elucidate the role of endogenous endothelin on DNA synthesis in endothelial cells, we have investigated the effects of rabbit anti-ET gamma globulin on DNA synthesis in cultured human vascular endothelial cells. DNA synthesis was markedly inhibited by anti-ET gamma globulin in a concentration dependent manner in the presence of fetal calf serum(FCS) (x5000;34%, x2500;54%, x1000;70%), but not in the absence of FCS. These data suggest that endogenous ET modulates FCS-stimulated DNA synthesis in an autocrine fashion.

Animals↗

PubMed1990

Rapid Ca2+ refilling system of intracellular store(s) in human vascular endothelial cells.

Using a fura-2 method, cytosolic Ca2+ concentration [( Ca2+]i) was measured in endothelial cell monolayers from human umbilical vein. In the presence of 1.5 mM Ca2+, bradykinin (BK) induced a rapid (within 15 sec) and dose-dependent (10(-8)-10(-6) M) increase in [Ca2+]i, consisting of an initial peak and a subsequent sustained phase. The pretreatment with 3 mM EGTA for 1 min caused a significant reduction in [Ca2+]i levels both of the basal (p less than 0.05) and BK-stimulated initial peak (p less than 0.001). However, the BK-stimulated initial peak was retained in magnitude for at least 5 min under the treatment with EGTA. In contrast, the sustained phase was completely abolished by EGTA treatment. The BK-stimulated Ca2+ transient, once having been completely inhibited by ionomycin (10(-6) M) in the presence of EGTA, was rapidly (within 2 min) recovered to the untreated level by replacing it with fresh medium containing 1.5 mM Ca2+. The present results indicated that BK mobilized Ca2+ from both intracellular and extracellular space(s) and suggest the presence of an extracellular Ca2(+)-dependent rapid refilling system of intracellular Ca2+ store(s) in human vascular endothelial cells.

Benzofurans↗

PubMed1990

Quantitative bone histomorphometry and circulating T lymphocyte subsets in postmenopausal osteoporosis.

To explore the influence of the immune system on the development of osteoporosis, 19 untreated postmenopausal women with osteoporosis were studied by means of quantitative histomorphometry of the ilium and an analysis of T lymphocyte subsets in the peripheral blood. Osteoporotic women had lower OKT3+ and OKT8+ counts and a higher OKT4+/OKT8+ ratio than nonosteoporotic control subjects. Linear regression analyses disclosed that the age of subjects correlated with bone mineral density (BMD; r = -0.634, p less than 0.01) and some of the histomorphometric parameters for bone formation (r = -0.694 to -0.467, p less than 0.01-0.05). The number of OKT4+ cells showed weak but significant negative correlation with the parameters for bone resorption (r = -0.549 to -0.462, p less than 0.05). In a multiple regression analysis, the advanced age, the increase in OKT3+, and the decrease in OKT4+ and OKT8+ counts were shown to be significant predictors for the decrease in BMD (R = 0.882, p less than 0.01). According to the regression formula obtained from the analysis, the parameters for bone formation were related only to the age of subjects whereas those for bone resorption were tightly associated with the number of OKT4+ and OKT8+ cells but not with the age of subjects. These results indicated that, in addition to the age factor, abnormalities of the peripheral T lymphocyte subsets, especially those of OKT4+ and OKT8+ cells, are closely associated with the decrease in bone mass in postmenopausal osteoporosis, supporting the causal relationship between T lymphocyte functions and the development of postmenopausal osteoporosis.

Aged↗

PubMed1990

Human PTH-(3-34) inhibited the effects of human parathyroid hormone-related protein on phosphate uptake in a cultured renal cell line (OK cells).

The action mechanism of hPTH and hPTHrP-(1-34) on phosphate uptake in opossum kidney (OK) cells was studied using [Nle8,18Tyr34]hPTH-(3-34)-NH2, a potent competivie inhibitor of adenylate cyclase-coupled PTH receptor. We examined the effects of hPTH-(1-34), hPTHrP-(1-34), and hPTH-(3-34) separately or in combination on the change in renal cyclic AMP production and phosphate uptake in OK cells. Both hPTH-(1-34) and hPTHrP-(1-34) stimulated intracellular cyclic AMP production to the same degree at concentrations between 10(-10) and 10(-7) M and inhibited phosphate uptake equipotently on a molar basis (27.5 +/- 2.0 and 33.2 +/- 1.2% inhibition at 10(-7) M, respectively). Both exogenous addition of (Bu)2cAMP and endogenous stimulation of cAMP by forskolin inhibited phosphate uptake in a dose-dependent manner. Cyclic AMP production induced by either hPTH-(1-34) or hPTHrP-(1-34) was inhibited by both [Nle8,18Tyr34]-hPTH-(3-34)-NH2 and [Tyr34]-hPTH-(7-34)-NH2. However, [Nle8,18Tyr34]hPTH-(3-34)-NH2 and [Tyr34]-hPTH-(7-34)-NH2 inhibited hPTH-induced cAMP production more strongly. The inhibitory action of phosphate uptake by hPTH-(1-34) and hPTHrP-(1-34) was prevented in the presence of a 100-fold greater concentration of [Nle8,18Tyr34]hPTH-(3-34)-NH2. The antagonistic action of [Nle8,18Tyr34]hPTH-(3-34)-NH2 on the inhibition of phosphate uptake induced by hPTH-(1-34) and hPTHrP-(1-34) became weaker with time (0-120 minutes), and [Nle8,18Tyr34]hPTH-(3-34)-NH2 did not antagonize the inhibition of phosphate uptake induced by hPTHrP-(1-34) at 120 minutes of incubation.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1990

Increase of bone mineral density by calcium supplement with oyster shell electrolysate.

The effect of calcium supplementation, in patients with osteoporosis is still a matter of controversy. Oyster shell electrolysate (OSE) was reported to raise serum calcium and increase urinary calcium excretion in vitamin D-deficient states more readily than calcium carbonate. Since the effect of calcium salts on osteoporosis depends heavily on its bioavailability, the effect of 900 mg/day calcium as OSE was tested in 12 elderly osteoporotic females, using radial bone mineral density measured by single photon absorptiometry and spinal trabecular bone density measured by quantitative computed tomography (QCT) as indicated, in comparison with 21 untreated controls in the same geriatric hospital. Radial bone mineral density significantly increased from the pre-test value after 12 and 24 months in subjects given OSE by paired t-test, whereas it fell significantly in the controls. The spinal QCT value on OSE did not change significantly in either the subjects under treatment with OSE, or the controls. Thus OSE may favorably influence osteoporosis by providing a readily available source of calcium.

Aged↗