Biomedical subjects

M K Drezner

Publications and source records attributed to M K Drezner.

99 records · Page 6Linked to original sources

PubMed1977

Osteomalacia due to 1alpha,25-dihydroxycholecalciferol deficiency. Association with a giant cell tumor of bone.

Oncogenic osteomalacia is a syndrome in which unexplained osteomalacia remits after resection of a coexisting mesenchymal tumor. We have investigated the mechanism by which a giant cell tumor of bone caused biopsy-proved osteomalacia in a 42-yr-old woman. The biochemical abnormalities were: hypophosphatemia; decreased renal tubular maximum for the reabsorption of phosphate per liter of glomerular filtrate; negative calcium and phosphorus balance; hyperaminoaciduria; and subnormal calcemic response to exogenously administered parathyroid hormone. Malabsorption, hypophosphatasia, fluorosis, and acidosis were excluded as causes of the osteomalacia. Serum 25-hydroxycholecalciferol was normal (27+/-1 ng/ml). However, the serum concentration of 1alpha,25-dihydroxycholecalciferol was low (1.6+/-0.1 ng/100 ml). Oral administration of physiological amounts of 1alpha,25-dihydroxycholecalciferol resulted in resolution of the biochemical abnormalities of the syndrome and healing of the bone pathology. We suggest that tumor-induced inhibition of 1alpha,25-dihydroxycholecalciferol synthesis caused the osteomalacia. The causal role of the tumor was proved by demonstrating that resection was accompanied by roentgenographic evidence of bone healing and maintenance of normal serum phosphorus; renal tubular maximum for the reabsorption of phosphate; calcium and phosphorus balance; aminoaciduria; and calcemic response to exogenous parathyroid hormone.

Adult↗

PubMed1977

Hypoparathyroidism: a possible cause of osteomalacia .

A 17 year old man with longstanding hypocalcemia and hyperphosphatemia presented with incapacitating bone pain and progressive weakness nad bowing of the legs. The serum abnormalities were due to idiopathic hypoparathyroidism as evidenced by a decreased serum concentration of parathyroid hormone and an appropriate rise in urinary cyclic AMP and phosphate excretion, and serum calcium concentration, in response to exogenously administered parathyroid extract. The serum concentration of 1,25-dihydroxycholecalciferol was appropriately decreased. The bone findings were due to osteomalacia as documented by physical findings, bone roentgenograms, and bone biopsy. Normal renal tubular function, blood pH, and serum concentration of 25-hydroxycholecalciferol and elevated serum alkaline phosphatase excluded the common causes of osteomalacia. The data are consistent with the hypothsis that lack of parathyroid hormone causes both hypocalcemia and a decreased serum concentration of 1,25-dihydroxycholecalciferol which, in turn, limit the availability of calcium and cause defective synthesis of bone matrix resulting in abnormal mineralization.

Adolescent↗

PubMed1976

Stimulation of cartilage macromolecule synthesis by adenosine 3',5'-monophosphate.

The role of cyclic AMP in the regulation of cartilage macromolecule synthesis in vitro was studied in pelvic cartilage from 10-12 day chick embryos. Incubation of cartilages in medium containing 0.5 mM cyclic AMP resulted in a 30% inhibition of 35SO4-2, [3H]leucine and [3H]uridine incorporation into proteoglycan, total protein and RNA, respectively. Higher concentrations of cyclic AMP had no greater effects. In contrast, butyrylated cyclic AMP derivatives (0.5-5.0 mM) added to the incubation medium stimulated (50-100%) the incorporation of these radiolabeled precursors into cartilage macromolecules. Theophylline, in concentrations (0.1-0.5 mM) which raise intracellular cyclic AMP, also increases the incorporation of radiolabeled precursors into macromolecules. The data indicate that exogenous cyclic AMP and butyrylated cyclic AMP derivatives have paradoxical effects on cartilage macromolecule synthesis. Butyrylated cyclic AMP derivatives, not exogenous cyclic AMP, mimic the effects of intracellular cyclic AMP. Incubation of embryonic chicken cartilage with exogenous cyclic AMP results in the extracellular degradation of the cyclic AMP to adenosine. Adenosine (0.125 mM) inhibits precursor incorporation into cartilage macromolecules. The metabolism of exogenous cyclic AMP generates sufficient adenosine to account for the observed inhibitory effects of exogenous cyclic AMP on cartilage macromolecule synthesis. Butyrylated cyclic AMP derivatives are not degraded during incubation with cartilage. The data indicate that cartilage is a tissue in which the effect of cyclic AMP is to stimulate anabolic processes.

Animals↗

PubMed1976

Renal cyclic adenosine monophosphate: an accurate index of parathyroid function.

Measurement of total urine cyclic 3':5'-adenosine monophosphate (cyclic AMP) only incompletely discriminates between normal, hyperparathyroid, and nonparathyroid hypercalcemic patients. Only a fraction of total urine cyclic AMP is contributed by parathyroid hormone (PTH) action on the proximal nephron (renal cyclic AMP); the remainder is derived from plasma by glomerular filtration. We dtermined total urine and plasma cyclic AMP and PTH (by carboxy-terminal specific radioimmunoassay) in control, hyperparathyroid, nonparathyroid hypercalcemic, and surgically hypoparathyroid patients. Renal cyclic AMP was calculated as total urine cyclic AMP minus the filtered component. Of these determinations, only renal cyclic AMP segregated normal from hyperparathyroid, and hyperparathyroid from nonparathyroid hypercalcemic patients with complete accuracy. These data suggest that measurement of renal cyclic AMP provides an accurate index of parathyroid activity and allows clinical discrimination and appropriate treatment of the sub-groups of patients with malignancy and nonparathyroid hypercalcemia from those with hyperparathyroidism.

Adult↗

PubMed1976

1,25-Dihydroxycholecalciferol deficiency: the probable cause of hypocalcemia and metabolic bone disease in pseudohypoparathyroidism.

Pseudohypoparathyroidism (PsH) is a genetic disease characterized by hypocalcemia, hyperphosphatemia, and metabolic unresponsiveness to parathyroid hormone (PTH). The administration of PTH elicits neither a significant rise in serum calcium (calcemic response) nor a decrease in the renal tubule reabsorption of phosphorus (phosphaturic response). The diminished phosphaturic response is due to an inability of PTH to generate cyclic AMP in renal tubule cells. We investigated the question of whether hypocalcemia and deficient calcemic response to PTH are due to a similar cyclic AMP defect in bone or to an acquired vitamin D deficiency. Four patients were studied. The active form of vitamin D (1,25-dihydroxycholecalciferol) was measured in 3 and was low. Treatment with vitamin D2 restored the serum calcium and the calcemic response to PTH to normal without changing the impaired renal response. Bone biopsy was performed in 2 patients and showed morphologic evidence of increased osteoclastic activity and osteomalacia. The data indicate that the hypocalcemia and bone disease in PsH are due to active vitamin D deficiency, possibly resulting from the genetic renal lesion.

Adult↗

PubMed1975

Stimulation of cartilage amino acid uptake by growth hormone-dependent factors in serum. Mediation by adenosine 3':5'-monophosphate.

The effects of growth hormone-dependent serum factors on amino acid transport and on cartilage cyclic AMP levels in embryonic chicken cartilage were studied in vitro. Cartilages incubated in medium containing rat serum showed a significantly greater uptake of alpha-amino [1-14C] isobutyrate or [1-14C] cycloleucine than control cartilages incubated in medium alone. Normal rat serum (5%) added to the incubation medium also caused an increase in cartilage cyclic AMP content (from as little as 23% to as much as 109%). The factors in serum which increase cartilage cyclic AMP and amino acid uptake are growth hormone dependent, since neither growth hormone itself nor serum from hypophysectomized rats restores these serum factors. Studies comparing the ability of sera with varying amounts of growth hormone-dependent factors to stimulate amino-aminoisobutyrate transport and to increase cartilage cyclic AMP show a striking linear correlation between the two effects (r=0.977). Theophylline and prostaglandin E1, WHICH RAISE CARTILAGE CYCLIC AMP also increase amino-aminoisobutyrate transport. Exogenous cyclic AMP, N6-monobutyryl cyclic AMP and n6, 02'-dibutyryl cyclic AMP increase cartilage amino-aminoisobutyrate transport. The data are compatible with the thesis that growth hormone-dependent serum factors increase cartilage amino acid transport by elevating cartilage cyclic AMP.

Amino Acids↗

PubMed1975

Inhibition of chondromucoprotein synthesis: an extraneuronal effect of nerve growth factor.

Nerve growth factor (NGF) is probably made by many extraneural tissues and some mesenchymal tumors. The present study investigated the effects of NGF on the in vitro synthesis of macromolecules by embryonic chicken cartilage. Cartilage deoxyribonucleic acid and ribonucleic acid synthesis as estimated by radioactive thymidine and uridine incorporation were unaltered by NGF. Chondromucoprotein synthesis as determined by 35SO4 incorporation into cartilage proteins was significantly inhibited by as little as 2 mug/ml of NGF and markedly inhibited (65-82 percent) by 20 mug/ml. Total cartilage protein synthesis as indicated by the incorporation of radioactive leucine was slightly (14 percent) but significantly inhibited by NGF. Fractionation of cartilage proteins into collagen-rich and chondromucoprotein-rich fractions and further purification by polyacrylamide gel electrophoresis demonstrated that all of the inhibition of leucine incorporation was due to the inhibition of chondromucoprotein synthesis. Thus NGF causes a selective and unique inhibition of cartilage chondromucoprotein synthesis.

Animals↗

PubMedDate not supplied

Newer knowledge of vitamin D and its metabolites in health and disease.

Renewed interest in vitamin D, over the past several years, has resulted in increased knowledge of (1) the metabolic pathways which result in production of an active metabolite, (2) the role of its various metabolities at target tissues, and (3) its interaction with other control systems in the maintenance of calcium/phosphorus homeostasis. Presently, a role for 1, 25-(OH)2 D3 can be identified in the regulation of (1) calcium and phosphorus absorption from the intestine, (2) PTH production, and (3) calcium mobilization from bone (in conjunction with PTH). Several other actions at the kidney, muscle and other organs have been suggested but not proven. In contrast, the actual process of bone mineralization may be dependent, in part, on 25-(OH) D3. Despite these major advances in our knowledge, many gaps remain and controversial data continues unresolved. However, application of this new information to analysis of a wide variety of disease states has resulted in remarkable progress in appreciation of the pathogenesis and appropriate treatment for these diseases. Nonetheless, continued research promises further advances and more precise definition of disease states as well as delineation of the therapeutic role of Vitamin D metabolites in their treatment.

Bone and Bones↗

PubMedDate not supplied

Vitamin D and prostate cancer: a prediagnostic study with stored sera.

This study evaluates the risk of prostate cancer in relation to serum levels of the major vitamin D metabolites, 25-hydroxyvitamin D (25-D3) and 1,25-dihydroxyvitamin D (1,25-D). Between 1964 and 1971, more than 250,000 serum samples were collected from members of the Kaiser Permanente Medical Care Plan in Oakland and San Francisco and stored for future use. Levels of 25-D and 1,25-D were measured in samples from 90 black and 91 white men diagnosed with prostate cancer before December 31, 1987 and controls individually matched on age, race, and day of serum storage. Mean serum 1,25-D was 1.81 pg/ml lower in cases than in matched controls (P = 0.002). Risk of prostate cancer decreased with higher levels of 1,25-D especially in men with low levels of 25-D. However, mean 25-D was not significantly different in cases and controls. The association of lower 1,25-D with prostate cancer was found in men above the median age of 57 years at serum storage but not younger men and was similar in black and white men. In men > or = 57 years of age, 1,25-D was an important predictor of risk for palpable and anaplastic tumors but not for tumors incidentally discovered during surgery to treat the symptoms of benign prostatic hyperplasia or well differentiated tumors.

Adult↗