A comparison of the in vivo biochemical responses to exogenous parathyroid hormone-(1-34) [PTH-(1-34)] and PTH-related peptide-(1-34) in man.

PTH-related peptide (PTHrP) is one of the etiological factors associated with hypercalcemia of malignancy in humans and rodents. In both in vivo and in vitro animal systems its actions mimic those of PTH; however, its bioactivity in humans has not previously been assessed. Therefore, we compared the actions of the synthetic human (h) analogs hPTHrP-(1-34) and hPTH-(1-34) when given by iv infusion to 15 healthy subjects, aged 25 +/- 3 yr. Three 12-h test infusions were given to each subject in the order: hPTH-(1-34) at a dose of 8 pmol/kg.h, an equimolar dose (8 pmol/kg.h) of PTHrP-(1-34) (low dose), and a 10-fold higher dose (80 pmol/kg.h) of hPTHrP-(1-34) (high dose). PTH infusion resulted in significant increases from basal values in serum total ionized calcium, urinary phosphate and cAMP, and serum 1,25-dihydroxyvitamin D3 [1,25-(OH)2d3]. No significant increases from basal values in any of these variables were observed during low dose PTHrP infusion. However, a 10-fold higher dose of PTHrP significantly increased serum calcium from 2.36 +/- 0.07 to 2.63 +/- 0.16 mmol/L (P less than 0.003), ionized calcium from 1.22 +/- 0.03 to 1.39 +/- 0.09 mmol/L (P less than 0.003), urinary phosphate from 0.21 +/- 0.19 to 0.31 +/- 0.16 mmol/L glomerular filtrate (P less than 0.05), urinary cAMP from 37 +/- 18 to 53 +/- 28 nmol/L glomerular filtrate (P less than 0.01), and serum 1,25-(OH)2D3 from 29.8 +/- 12.1 to 46.0 +/- 20.3 pmol/L (P less than 0.01). For each variable these changes were statistically equivalent to the increases observed during PTH infusion. The molar concentrations of circulating immunoreactive PTH-(1-34) and PTHrP-(1-34) (at the higher dose) achieved during infusion were at a ratio of 1:3. These results suggest that the in vivo actions of synthetic hPTHrP-(1-34) are comparable to those of hPTH-(1-34), but its biological activity after infusion may be less than that of hPTH-(1-34). Moreover, the increased concentrations of serum 1,25-(OH)2D3 observed with administration of hPTHrP-(1-34) are unlike the changes seen in hypercalcemia of malignancy in which levels of this vitamin D metabolite are frequently depressed.     

Chronic acidosis with metabolic bone disease: Effect of alkali on bone morphology and vitamin D metabolism

Chronic metabolic acidosis and osteomalacia developed in two patients following urinary diversion. Good clinical, biochemical, and histologic responses were seen following treatment with alkali alone (vitamin D was not given), despite the presence of markedly impaired glomerular filtration in one of the patients. Plasma 25-hydroxy vitamin D and 1α,25-dihydroxyvitamin D concentrations were normal before and during treatment in one of the patients and in the other were low before and normal during treatment. The results show that successful treatment of the osteomalacia of chronic acidosis is not necessarily accompanied by changes in the plasma levels of vitamin D metabolites and that even when marked glomerular dysfunction coexists with acidosis and osteomalacia, treatment with alkali may be more appropriate than the administration of vitamin D analogues.     

Fractionated total-body irradiation and high-dose etoposide as a preparatory regimen for bone marrow transplantation for 94 patients with chronic myelogenous leukemia in chronic phase

Ninety-four consecutive patients with chronic myelogenous leukemia in first clinical chronic phase, median age of 34.0 years (range, 6.8 to 52.4 years), with a histocompatible sibling donor, were treated with fractionated total body irradiation (1,320 cGy) and high-dose etoposide (60 mg/kg) followed by allogeneic bone marrow transplantation (BMT). The median time from diagnosis to BMT was 7.0 months (range, 2.3 to 72.0 months). Sixty patients were treated before BMT with hydroxyurea alone, four patients with busulfan alone, one patient with interferon alone, and the other 29 patients were treated with various combinations of these drugs. Cumulative probabilities of overall survival, event- free survival, and relapse at 5 years were 73%, 64%, and 14%, respectively. The median follow-up time for surviving patients was 38 months, ranging from 12 to 88 months. By stepwise Cox regression analysis, significant prognostic variables were age at transplant, acute graft-versus-host disease > or = grade II, cytomegalovirus- associated interstitial pneumonitis, and years from diagnosis to BMT.     

分枝桿菌(Mycobacterium sp.M12)降解甾醇侧链的研究

分枝杆菌(Mycobacterium sp.M12)能将胆固醇,3β-乙酰氧基胆固醇,谷甾醇以及3β-乙酰氧基谷甾醇降解成△³-雄甾烯-3,17-二酮(4AD)及少量的△^1.4-雄甾烯-3,17-二酮(ADD)。4AD的收率分别为69%,70%,26%,22%。对该菌株降解胆固醇侧链的最适条件进行了研究。     

Selective damage to erythroblasts by 55-Fe

The low energy and short range of 55-Fe Auger electrons were utilized in mice to deliver lethal intracellular radiation to iron-incorporating erythropoietic precursors with minimal radiation damage to other bone marrow cells. The ensuing intramedullary, selective erythropoietic death was demonstrated by absolute and differential bone marrow cell counts and by decreased blood uptake of 59-Fe. The decreased number of colony-forming units in spleen colony assay and the decreased ability of tranplanted bone marrow to protect fatally irradiated mice shows that the bone marrow was partially depleted of pluripotent stem cells. These data are interpreted to indicate an increased pluripotent stem cell utilization in response to increased demand for differentiation of stem cells along the erythropoietic pathway.     

Certain vitamin D metabolites potentiate the expression of parathyroid hormone bioactivity

With the development of a sensitive bioassay for the skeletal effects of parathyroid hormone (PTH), it has become possible to investigate the possible interaction between PTH and vitamin D3 metabolites. This assay is based on the stimulation of glucose-6-phosphate dehydrogenase (G6PD) activity in either the hypertrophic chondrocytes of the growth plate or the osteoblasts lining the metaphyseal trabeculae of rat metatarsals. The response to PTH is paralleled by the activity of dibutyryl cAMP. None of the vitamin D3 metabolites tested had any effect on enzyme activity when tested by themselves. However, both 1,25(OH)2D3 and 25(OH)D3 caused a dose-related potentiation of the response to PTH. Neither 1,24,25(OH)3D3 nor 1,25(OH)2D3 26,23-lactone potentiated the response to PTH. Because this potentiation of the response to PTH occurs after only 8 minutes, it is suggested that it represents a nongenomic response to the vitamin D3 metabolites.