摘要:

AbstractWe studied the effect of the intravenous administration of the bisphosphonate APD in 9 patients with Paget's bone disease. The medication was given in a daily dose of 25 mg for 7 days in 0.9% saline infusion over 2 hours. At the end of treatment a significant fall of serum calcium and phosphate was observed. The urinary excretion of calcium decreased markedly and the serum levels of the mid‐molecule PTH fragment increased from (mean ± SE) 85 ± 11 to 122 ± 16 pg/ml (p<0.05). A marked and rapid decline in the hydroxyprolinuria was observed from 297 ± 61 mg/24 h to 194 ± 51 mg/24 h (p<0.01); meanwhile the serum alkaline phosphatase decreased from 102 ± 22 to 84 ± 21 KAU (p<0.05). The effect of ADP on suppression of hydroxyprolinuria varied markedly from +1 to ‐81% and was negatively related to the basal hydroxyprolinuria (r= ‐0.90;p<0.001). The duration of the bone turnover suppression was short. A relapse greater than 30% in hydroxyprolinuria was observed in 6 of 8 patients 2 to 3 months after APD withdrawal.The short‐term intravenous administration of ADP is a useful means to rapidly suppress the activity of Paget's bone disease. However, further studies should determine the optimum dose, the length of treatment, and the need to associate oral therapy to induce a prolo

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020402

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractWe studied the effects of the intravenous or oral administration of aminohexane diphosphonate (AHDP) in 42 patients with active Paget's disease of bone. Treatment of mouth (400 mg daily for 1 month) or intravenously (25 mg or 50 mg daily for 5 days) induced marked suppression of biochemical indices of disease activity. Urinary excretion of hydroxyproline fell to 39 and 42% of pretreatment values (oral and IV treatments respectively), and was followed by a similar decrease in the serum activity of alkaline phosphatase. In both groups of patients, disease activity remained suppressed for the 6 months of followup, and pain improved in 34 out of 37 patients who had bone pain attributed to Paget's disease. Both biopsies indicated that osteoblast and osteoclast numbers decreased with no adverse effects on mineralization. Neither regime was associated with significant side effects. We conclude that short courses of AHDP provide a promising treatment for the long‐term control of Paget's diseas

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020403

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractThe calcium/phosphatidylserine (PS)‐stimulated phosphorylation of endogenous proteins in the 100,000 ×gparticulate fraction from neonatal mouse calvaria was investigated. EGTA selectively inhibited the phosphorylation of a 20K protein. The phosphorylation of this 20K protein was stimulated by calcium and by PS. The combination of calcium plus PS increased the phosphorylation of the 20K protein more markedly than either calcium or PS alone. Parathyroid hormone (PTH) (100nM) treatment of calvaria rapidly altered the phosphorylation of the 20K protein in a time‐dependent manner. The PTH treatment time course demonstrated that after 5 minutes thein vitrophosphorylation of the 20K protein was markedly enhanced, after 15 minutes the 20K protein was not as heavily phosphorylated, and after 30 minutes thein vitrophosphorylation of the 20K was less than control. Our results demonstrate the presence of calcium/PS‐stimulated phosphorylation in bone tissue and a rapid effect of PTH on this phosphory

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020404

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractStudies of the effects of acidosis and dietary calcium on 25‐hydroxyvitamin D3(25OHD3) metabolism were conducted utilizing assays of mitochondrial 1‐hydroxylase and 24‐hydroxylase activity following 96 hours of acid loading. The results showed decreased 1‐hydroxylase (206 ± 6 vs. 132 ± 22 fmol min−1mg/mitochondrial protein−1,p<0.01), augmented 24‐hydroxylase (48 ± 14 vs. 180 ± 30 fmol min−1mg−1,p<0.001) and increments in plasma calcium and phosphate following acidosis. High calcium diet also increased 24‐hydroxylase activity (48 ± 14 vs. 160 ± 24 fmol min−1mg−1,p<0.001) and plasma calcium, but decreased plasma phosphate. The extramitochondrial concentrations of calcium, potassium, and phosphate which maximally stimulated the hydroxylasesin vitrowere not altered by thein vivodietary perturbations. The increments in 1‐hydroxylase and 24‐hydroxylase resulting from the presence of calcium, potassium, or phosphate in optimal concentrations (10−5M, 100mM, and 100mM, respectively) were changed by both acid loading and high calcium diet, decreasing in the case of 1‐hydroxylase and increasing in that of 24‐hydroxylase. The data indicate that the suppression of 1‐hydroxylase and augmentation of 24‐hydroxylase following these dietary perturbations may depend on both changed total enzyme capacity and altered enzyme sensitivity to extramitochondrial ions and are consistent with medi

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020405

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractTransforming growth factors (TGFs) have been implicated in the pathogenesis of the hypercalcemia in malignancy (HM). In order to evaluate the role of these growth factors (epidermal growth factor (EGF) and TGF‐α acting via the EGF receptor) in the development of HM, we studied the effect of 2 doses of EGF (0.1 and 0.3 μg/g/day) given for 7 days as a continuous infusion on serum and urine calcium in athymic mice. These infusions had no effect on serum and urine Ca values in this study. In order to assess the biological activity of the infused EGF, other known effects on gastric and pancreatic weights were evaluated. EGF‐infused animals had significantly greater gastric and pancreatic weights than controls. Thus, EGF infusion into mice in doses which elicited known biological effects failed to have an effect on serum and urine Ca. An infusion of bovine parathyroid hormone 1–34 at the dose of 0.1 μg/g/day resulted in significant hyper

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020406

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractThein vitromitotic response of rat thymic lymphocytes to hPTH(1–34), hPTH (1–38), and 8,18 NIe hPTH(1–34) exhibits a dependency upon extracellular calcium. Removal of extracellular calcium or the addition of Verapamil (5 μg/ml) or trifluoroperazine (10 μM) abrogated the mitotic response. Mitogenic concentrations of 8,18 NIe hPTH(1–34) increased calcium 45 uptake from 4.49 ± 0.25 to 8.23 ± 0.75 pMol/106cells/min. The intracellular calcium concentration, measured by Quin 2 fluorescence, also increased after addition of 8,18 NIe hPTH(1–34).Parathyroid hormone‐induced activation could not be demonstrated in an otherwise responsive thymocyte membrane adenylate cyclase. In intact cells mitogenic levels of 8,18 NIe hPTH(1–34) decreased intracellular cyclic AMP content. This response was blocked by both 3‐isobutyl 1‐methyl xanthine and trifluoroperazine, and may indicate activation of calcium‐dependent phosphodiesterase.We conclude that PTH stimulates thymic lymphocyte proliferation independently of cyclic AMP, and that changes in cellular calcium homeostasis are intimately involved in the action of PTH. In all of the assays employed, the hitherto antagonistic analogue 8,18 NIe 34 Tyr bPTH(3–34)amide proved to be an agonist. We postulate that the receptor utilized for this PTH action may not exhibit classical PTH structu

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020407

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractIt is unknown if osteoclasts derived from animals at different developmental stages differ. To study this question, we used a long‐term baboon marrow culture system in which osteoclast‐like multinucleated cells (MNC) are formed. Fetal, newborn, or adult baboon marrow cultures were tested to determine if they differ in their responsiveness to osteotropic hormones. In fetal and newborn marrow cultures 1,25‐dihydroxyvitamin D3(1,25D3) at 10−10Msignificantly increased MNC formation with a maximal effect seen at 10−9M.Higher concentrations of 1,25D3progressively decreased MNC formation. In contrast, in adult baboon marrow cultures, 10−9M1,25D3was required to significantly increase MNC formation, with a maximal affect at 10−8M1,25D3. Calcitonin (25–200 ng/ml) inhibited MNC formation in fetal, newborn, or adult baboon marrow cultures treated with 1,25D3in an identical manner. The effects of 1,25D3on granulocyte‐macrophage progenitor cells (CFU‐GM), the probable precursors of MNC, were identical in fetal and adult baboon marrow cultures, with a significant inhibition of CFU‐GM colony formation at 10−8M1,25D3. These results suggest that 1) osteoclast precursors are more sensitive to some osteotropic hormones during the fetal and newborn periods, and 2) differences in the 1,25D3sensitivity of osteoclast‐like MNC formation in fetal, newborn, and adult baboon marrow cultures are not due to effects on early proliferating precursors but may result from effects of 1,25D3on fusion of

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020408

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractA newly developed calcium‐sensitive dye, Fura‐2, was employed in dispersed bovine parathyroid cells to study the effects of extracellular calcium and magnesium on cytosolic calcium concentration and parathyroid hormone (PTH) release. In comparison with control cells, Fura‐2‐loaded parathyroid cells showed the same maximal rate of PTH release, set‐point for extracellular Ca++(the calcium concentration producing half of the maximal inhibition of PTH release), and maximal inhibition of PTH release (71.6%) by high extracellular Ca++. At an extracellular Mg++concentration of 0.5mM, raising extracellular Ca++in a stepwise fashion from 0.5mMto 2.0mMproduced a dose‐dependent, statistically significant (p<0.01) increase in cytosolic Ca++from 198 ± 24nM(0.5mMCa++) to 411 ± 21nM(2.0mMCa++) which closely paralleled the concomitant decrease in PTH release. An elevation of extracellular Mg++from 0.5mMto 5mM, at an extracellular Ca++of 0.5mM, resulted in a transient spike of cytosolic Ca++which lasted for approximately 30 seconds, followed by a small but stable increase in the cytosolic Ca++concentration (174 ± 7nMvs. 237 ± 10nM, n= 4,p<0.01). Prior removal of extracellular calcium by addition of an excess of EGTA did not abolish the transient spike induced by high extracellular magnesium concentrations in Fura‐2‐loaded cells, suggesting that this rapid increase in cytosolic Ca++arises, at least in part, from intracellular stores of Ca++. This is supported by the observation that pretreating cells with ionomycin resulted in disappearance of the magnesium‐induced spike. In parallel experiments, the values for cytosolic calcium concentration at high and low extracellular calcium and magnesium concentrations in cells loaded with Fura‐2 were comparable to those in cells loaded with Quin‐2. These results show that Fura‐2 may be employed to measure the cytosolic Ca++concentration in dispersed bovine parathyroid cells and that extracellular Ca++and Mg++produced sustained increases in cytosolic Ca++in cells loaded with this dye which are comparable to those seen with Quin‐2‐loaded cells. In addition, however, probably because of the lower loading concentrations possible with Fura‐2, cells loaded with this dye show Mg++‐induced spikes in intracellular Ca++, resulting, in part, from release of intracellular Ca++. These Ca++transients support other data suggesting the possibility of an extracellular divalent cation receptor on parathyroid cells, which may produce some of its effects on parathyroid functi

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020409

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractIn this study we investigated whether parathyroid hormone (PTH) can produce relaxation of gastrointestinal (GI) smooth muscle as it has been reported to do for vascular and uterine smooth muscle. Muscle tissue preparations from rat stomach, duodenum, ileum, or colon were mounted in a 37°C tissue bath and perfused with oxygenated medium. Changes in isometric tension were recorded with a force‐displacement transducer connected to a polygraph. Decreases in either resting tension or agonist‐induced tension (0.5–1.0 μMacetylcholine or carbachol) were observed within 1–2 min of PTH addition and were reversible upon removal of the peptide. All GI regions tested were responsive to PTH. Synthetic rPTH‐(1–34) (0.1–100nM) produced a dose‐dependent relaxation of both fundic (ED50= 5.2nM) and colonic (ED50= 2.5nM) muscle strips. At 100nM, a 90% decrease in fundic tension and a 70% decrease in colonic tension were seen. At 100nM, bPTH‐(1–34), but not bPTH‐(7–34) or rat calcitonin gene‐related peptide, also was effective in relaxing fundic or colonic muscle. Similarly, in the fundic muscle, 500nMbPTH‐(3–34) alone was ineffective, but it inhibited the effect of 5nMrPTH‐(1–34) when both peptides were tested in combination. Likewise, 100nMbPTH‐(3–34) also inhibited the relaxation induced by 5, 10, or 100nMbPTH‐(1–34). The results show PTH to be highly effective in nanomolar concentrations in causing relaxation of GI smooth muscle. The findings suggests that rat GI smooth muscle possesses receptors for PTH and indicate a potential role for

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020410

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY

摘要:

AbstractBone γ‐carboxyglutamic acid (Gla)‐containing protein (BGP or osteocalcin) and 44 kDa bone phosphoprotein (44K BPP, also called Sialoprotein I or osteopontin) have been localized at the ultrastructural level in osteoblasts from woven bones of newborn rats. Frozen, undecalcified sections of periodate‐lysine‐paraformal‐dehyde fixed specimens were incubated with affinity purified, monospecific antibodies against BGP or 44K BPP. The sites of the antigen‐antibody reaction were demonstrated by the avidin‐biotin‐peroxidase complex method using the Hanker‐Yates reagent as a peroxidase substrate. In some cases immunostaining could only be achieved after detergent treatment. The immunostained sections were then flat‐embedded in Epon 812 and processed for electron microscopy. Strong specific intracellular labeling was obtained with both antibodies, but the patterns of staining differed significantly: BGP antigenicity was mainly located in the endoplasmic reticulum (ER), whereas 44K BPP behaved as a Golgi‐specific antigen. In both cases, however, we found no evidence for immunostained secretory vesicles. There was no correlation between the expression of BGP by osteoblasts and the morphological aspect of these cells, their apparent degree of polarization with respect to the bone matrix, or their relation with

ISSN:0884-0431    

DOI:10.1002/jbmr.5650020411

出版商:John Wiley and Sons and The American Society for Bone and Mineral Research (ASBMR)    

年代:1987

数据来源: WILEY