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Biomedical subjects

S L Teitelbaum

Publications and source records attributed to S L Teitelbaum.

At least 181 records · Page 10Linked to original sources
PubMed1982

Cystic parathyroid gland hyperplasia--hyperparathyroidism presenting as a neck mass.

Hyperparathyroidism may occasionally present as a neck mass resulting from cystic change in a parathyroid adenoma. We report an unusual instance of hyperparathyroidism presenting as a palpable, but asymptomatic hyperplastic parathyroid gland cyst. We conclude that hyperplastic parathyroid glands may undergo cystic degeneration resulting in a palpable neck mass; and that all functional parathyroid gland cysts are not necessarily adenomas. Therefore, during parathyroidectomy procedures, biopsy material from at least one additional parathyroid gland should be obtained.

Aged↗
PubMed1982

Calcium homeostasis in chronic streptozotocin-induced diabetes mellitus in the rat.

Calcium homeostasis was studied in freely fed control, streptozotocin diabetic, long-term and short-term insulin-treated diabetic rats 7 wk after the induction of diabetes. In contrast to the short-term (5-12 day) diabetic rat model, intestinal absorption of calcium was markedly enhanced in chronically insulin-deficient animals. Moreover, conventional balance studies showed that these animals were in positive calcium balance despite severe hypercalciuria. Intestinal hyperabsorption of calcium in long-standing diabetic rats occurred despite low levels of circulating 1,25-dihydroxyvitamin D and hypercorticosteronism and was attended by hypercalcemia and suppression of both plasma parathyroid hormone (PTH) and urinary cyclic 3',5'-AMP (cAMP). Long-term insulin replacement completely normalized the intestinal hyperabsorption of calcium, corrected the plasma calcium, and significantly increased circulating PTH and urinary cAMP excretion. Insulin therapy also corrected the decreased plasma 1,25-dihydroxyvitamin D observed in untreated diabetic animals. Intestinal hyperabsorption of calcium appeared to be only partially corrected by short-term insulin therapy. The accumulated results reveal decided differences in calcium homeostasis and hormonal response between the rats with long-standing diabetes and those with diabetes of short duration.

Animals↗
PubMed1982

Differential action of the bisphosphonates (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and disodium dichloromethylidene bisphosphonate (Cl2MDP) on rat macrophage-mediated bone resorption in vitro.

The bisphosphonates (3-amino-1-hydroxypropylidene)-1,1-bisphosphonate (APD) and disodium dichloromethylidene bisphosphonate (Cl(2)MDP) effectively inhibit the accelerated bone resorption associated with some skeletal disorders, e.g., Paget's disease. However, it has not been established whether these compounds exert their inhibitory effect by rendering the bone mineral more resistant to degradation, by diminishing the activity of resorbing cells, or through some combination of both activities. In this study, we have tested these possibilities using an in vitro resorption assay system consisting of elicited rat peritoneal macrophages co-cultured with particles of (45)Ca-labeled, devitalized rat bone. This assay system permits the quantitative assessment of the action of APD and Cl(2)MDP on the two major phases of bone resorption (cell-substrate attachment and osteolysis) under circumstances where the drugs are present continuously or, most importantly for the issues in question, after the separate pretreatment of the particles or the resorbing cells. Our data indicate that (a) Both APD and Cl(2)MDP at concentrations >/=5 x 10(-6) M diminish macrophage-mediated (45)Ca release (i.e., bone resorption) in a log dose-dependent fashion. (b) A 10-min pretreatment of bone particles with either bisphosphonate (P-C-P) similarly inhibits resorptive activity, but is most pronounced with Cl(2)MDP. However, only APD is effective in reducing resorption when cells are preincubated (for 24 h) with P-C-P. (c) In cultures containing both labeled and unlabeled bone, significant inhibition occurs only when the labeled particles are coated with P-C-P (indicating that the action of P-C-P-treated bone is highly localized). (d) P-C-P does not diminish cell-bone particle attachment, an essential step in the resorptive process. On the other hand, delaying the addition of P-C-P until after cell-bone attachment is completed significantly reduces the resorption-inhibiting effect of these compounds. (e) Cl(2)MDP reduces culture DNA content in proportion to its inhibitory effect on resorption, and both the inhibitory and cytotoxic actions of this P-C-P are dependent upon the presence of bone. On the other hand, APD is cytotoxic only at very high concentrations (10(-4) M), acts independently of the presence of bone, and inhibits resorption without killing cells. We conclude that the mechanisms of action of APD and Cl(2)MDP are markedly different. Cl(2)MDP is a potent cytotoxin in the presence of bone and apparently exerts its inhibitory effect in this manner. APD is noncytotoxic at levels adequate to suppress resorption and, therefore, must inhibit macrophage activity by some other mechanism. Neither P-C-P appears to limit resorption by decreasing the solubility of mineralized bone matrix.

Animals↗
PubMed1982

The relationship of monocytic cells to the differentiation and resorption of bone.

Osteogenesis in the developing limb is, as elsewhere, the result of two functionally integrated processes, bone matrix synthesis and matrix degradation. The latter process is a manifestation of the resorptive activity of osteoclasts (OCs), multinucleated giant cells which arise by fusion of mononuclear, blood-borne precursors. For the past several years, we have focused our efforts on several different aspects of OC development and differentiation. These efforts have included observations on patients with osteopetrosis, an analysis of monocyte (OC precursor) chemotaxis in response to bone matrix proteins, and the use of histochemical and bone grafting techniques to establish the lineage and expression of the osteoclast phenotype in the avian embryonic limb. Here, we (1) briefly review the evidence establishing the hematopoietic and probable monocytic origin of OCs, (2) present new data on the role of L-gamma-carboxyglutamic acid in osteocalcin-evoked chemotaxis and (3) describe the time course and likely developmental relationships between the appearance of circulating OC precursor cells, osteoclast differentiation, and the formation of mineralized bone matrix in the chick embryo. The results of the latter study indicate that OC differentiation is initiated by contact between precursor cells and mineralized bone, and suggest that the expression of the OC phenotype is dependent upon proteins or glycoproteins closely associated with bone mineral. We note that osteocalcin is one such protein.

Acid Phosphatase↗
PubMed1981

Ultrastructure of the rat epiphyseal growth plate following chronic ethanol ingestion.

We have previously demonstrated that ethanol has a direct toxic effect on the rat skeleton characterized by decreased trabecular bone volume. In the present study, we examined the ultrastructure of the distal radial epiphyseal growth plates in these same animals. Eight weeks of ethanol administration to 12 male rats results in serum alcohol levels of 140 mg/dl but did not alter the width or light microscopic appearance of the radial growth plate. Quantitative electron microscopy failed to demonstrate morphologic evidence of toxicity in the skeletal cells. We conclude that although ethanol appears to have a direct effect on rat bone characterized by enhanced resorption, toxicity is not attended by ultrastructural changes in the skeletal cells.

Animals↗
PubMed1981

Axial osteomalacia. Clinical, laboratory and genetic investigation of an affected mother and son.

Axial osteomalacia--a rare osteosclerotic bone disorder characterized by axial skeleton pain, coarsening of the trabecular bone pattern on radiographs of the axial but not appendicular skeleton, and osteomalacia on biopsy of a rib or iliac crest--has been reported in 10 apparently sporadic cases, all of which were in middle-aged or elderly Caucasian men. The etiology is unknown but has been postulated to be a bone cell defect. We describe the clinical, laboratory, pathologic and family study of a black mother and son with axial osteomalacia associated with polycystic liver and kidney disease. Investigation of the son suggested that radiographic osteosclerosis can be detected in early adulthood. Limited skeletal survey of his three children revealed no abnormalities. Examination of undecalcified iliac crest bone after in vivo tetracycline labeling revealed severe osteomalacia in the son despite normal circulating calcium, inorganic phosphate and vitamin D metabolite levels and persistently elevated alkaline phosphatase activity. Although osteoblasts appeared flat and inactive, histochemical studies showed intense alkaline phosphatase activity in the osteoblasts along most trabecular bone surfaces. Electron microscopy revealed intact matrix vesicles within unmineralized osteoid. The presence also of unexplained myopathy in the son--characterized by proximal muscle weakness, persistently elevated circulating creatine phosphokinase levels and pathogenic changes of myopathy on biopsy of quadriceps muscle--together with impaired bone mineralization, suggests that a disorder of vitamin D action may be involved in the pathogenesis of this unusual condition. Axial osteomalacia affects blacks as well as Caucasians, women as well as men, may be familial, and may perhaps be a developmental abnormality inherited in association with polycystic kidney and liver disease.

Adolescent↗
PubMed1981

Alkaline phosphatase activity in chronic streptozotocin-induced insulin deficiency in the rat: effect of insulin replacement.

Alterations in circulating alkaline phosphatase have been described in both man and the experimental animal with chronic insulin deficiency. We evaluated plasma and tissue alkaline phosphatase levels in freely-fed control, streptozotocin-induced diabetic and insulin-treated diabetic rats, seven weeks after the induction of diabetes. Circulating alkaline phosphatase activity was markedly elevated in the insulin deficient animal (p less than 0.001) and completely normalized following insulin administration. The elevated plasma alkaline phosphatase activity observed in the insulin deficient animals was heat-resistant and phenylalanine-sensitive, a pattern typical of the intestinal isoenzyme. Small intestinal alkaline phosphatase activity was significantly higher (p less than 0.01) in the diabetic animals, but comparable in the insulin-replaced and control rats. The intestinal isoenzyme activity was found to be strikingly insulin-sensitive; withholding insulin therapy for 36 hr prior to sacrifice resulted in an abrupt rise in both plasma and intestinal alkaline phosphatase values comparable to those observed in the insulin-deficient state. In contrast to these observations, skeletal alkaline phosphatase activity was decreased in the insulin deficient animal (p less than 0.01) and this abnormality was corrected by insulin replacement. Neither insulin deficiency nor insulin replacement resulted in any significant changes in the hepatic alkaline phosphatase isoenzyme.

Alkaline Phosphatase↗
PubMed1981

Skeletal sarcoidosis with osteopenia.

Diffuse osteopenia is not generally recognized as a radiological manifestation of skeletal sarcoidosis. Furthermore, the pathologic correlates of the skeletal abnormalities in sarcoidosis are poorly characterized. We quantitated the histomorphometric parameters of bone formation and resorption in a transiliac crest biopsy specimen from a patient with sarcoidosis, diffuse osteopenia, hypercalcemia, and hypercalciuria, who was treated only intermittently with corticosteroids and thiazides. Peritrabecular granulomas were associated with the histologic features of accelerated bone remodeling, namely: excess osteoid; increased numbers of osteoclasts and osteoblasts; increased osteoclastic resorbing surfaces; and increased bone formation rate. We conclude that the peritrabecular granulomas of skeletal sarcoidosis may result in rapid bone turnover with diffuse osteopenia which may contribute to the abnormalities of mineral metabolism.

Adult↗
PubMed1981

Malignant osteopetrosis: a disease of abnormal osteoclast proliferation.

Bone biopsies were obtained from two infants with the malignant form of congenital osteopetrosis. Non-decalcified histological sections of each biopsy contained vast numbers of osteoclasts occupying virtually the entire residual marrow space. Despite the apparent failure of normal bone resorption in both patients, the osteoclasts of one appeared histologically and ultrastructurally normal, exhibiting ruffled membrane formation and evidence of acid phosphatase synthesis and secretion. In contrast, the osteoclasts of the second patient were unusually shaped, abnormally large and contained no ruffled membranes. It is concluded that the bone marrow failure which appears in the malignant, as compared to the benign form of osteopetrosis, is at least in part due to replacement of hematopoietic precursors by osteoclasts. Furthermore, the different cytological appearance of the osteoclasts of each patient suggests that a spectrum of pathogenetic mechanisms may be responsible for the development of the disease. Finally, ruffled membrane formation by the osteoclasts of one patient calls into question the assumption that this morphological feature is invariably associated with bone resorption.

Biopsy↗
PubMed1981

Systemic mastocytosis associated with generalized osteopenia. Histopathological characterization of the skeletal lesion using undecalcified bone from two patients.

Although mast cell proliferation in the bone marrow frequently occurs in systemic mastocytosis and is often associated with radiographically detectable bone lesions, the pathologic correlates of the skeletal abnormalities are poorly characterized. We therefore examined three nondecalcified transiliac crest biopsy specimens from two patients with systemic mastocytosis and diffuse osteopenia with vertebral crush fractures. Marrow involvement included unusual mast cell aggregates, as revealed by metachromatic staining, that mimicked granulomas. Histomorphometric analysis or trabecular bone revealed accelerated bone remodeling or "turn over" characterized by osteoidosis, peritrabecular fibrosis, increased numbers of osteoblasts and osteoclasts, and an increase in osteoclastic resorbing surfaces. Our observations and review of the literature suggest that with the recent development of techniques for assessing undecalcified bone biopsy specimens, mastocytosis will probably be shown to be a more common etiology in "osteoporosis" than previously recognized. Metachromatic staining of the biopsy specimen should be a routine procedure in the investigation of any patient who undergoes diagnostic bone biopsy.

Adult↗
PubMed1981

Altered metabolic rhythm of rabbit osteoblasts by tetracycline.

To establish whether there are single or multiple pools of osteoblasts in rabbit bone, animals were injected with tetracycline on various schedules for 1-3 days. Metabolic restraints predicted that a multiple pool model would be feasible only if the percent labeled surfaces of trabecular bone (tibia) doubled when animals were injected on days 1 and 2, 1 and 3, or on days 1, 2, and 3. A single population would be indicated if the extent of labeled surfaces failed to double. Herein, 41.9 +2- 8.1% of bone surfaces labeled after a single injection, and only 60-68% of surfaces labeled after injections on the other schedules. The data inferred tht serial pulse tetracycline injections at 24h intervals caused a shift in the activities of a single population of osteoblasts and their progenitor cells.

Animals↗
PubMed1981

Glucocorticoid enhancement of bone resorption by rat peritoneal macrophages in vitro.

The issue of the direct action of glucocorticoids on bone resorption was addressed in a model system consisting of a pure (99%) population of putative osteoclast precursors, namely thioglycollate-elicited rat macrophages cocultured in vitro in devitalized rat bone particles which had been prelabeled in vivo with 45Ca. After 4 days in culture, these macrophages mobilized a net 20-30% 45Ca from bone. The addition of cortisol in physiological concentrations (10(-8) M) elicited significant (P less than 0.001) increases in isotope mobilization; optimal enhancement occurred at 10(-6) M and approximated the circulating level achieved with high dose glucocorticoid therapy. Other steroids, specifically aldosterone, 17 alpha- and beta-estradiol, 11-deoxycortisol, and progesterone, did not enhance the resorptive process. The augmentation of bone 45Ca mobilization by cortisol-treated macrophages was not due to protracted cell viability in culture or the increased avidity with which treated cells bind to bone. On the other hand, cortisol treatment was associated with stimulated protein and RNA synthesis, as evidenced by enhancement (P less than 0.001) of both [3H]leucine and [3H]uridine incorporation into treated cells. This association was also underscored by the observation that increased protein and RNA synthesis and enhanced mineral mobilization were inducible phenomena, i.e. phenomena that could be observed 48-72 h after cells were pretreated with cortisol. We conclude, therefore, that glucocorticoids can directly modify both the metabolism and the mineral-mobilizing activity of bone-resorbing cells.

Animals↗
PubMed1981

Isolated skeletal involvement in Cushing's syndrome: response to therapy.

A 38-yr-old male presented with severe symptomatic osteopenia secondary to adrenal hyperfunction without any clinical expression of Cushing's syndrome. The predominantly axial distribution of his osteopenia and the presence of rib fractures healing with abundant callus formation, despite insignificant elevations in serum alkaline phosphatase, were characteristic of glucocorticoid excess syndromes. The histological features of the pretreatment bone biopsy were typical of those associated with excess glucocorticoids, namely decreased quantities of nonmineralized bone matrix, reflecting sites of bone formation, and an increase in the number of osteoclasts, indicating enhanced bone resorption. Six weeks after adrenalectomy, repeat bone biopsy revealed a marked increase in bone matrix synthesis and a significant decrease in bone resorption. These observations suggest that stimulators of skeletal turnover, like sodium fluoride, may be inappropriate in the initial treatment of steroid-induced osteopenia after surgical cure and that vitamin D and calcium therapy offers a more rational approach. Furthermore, the importance of the routine evaluation of adrenal function in any patient presenting with osteopenia is stressed, as well as the fact that relatively isolated skeletal involvement, classically described in micronodular adrenal disease, is not necessarily peculiar to a specific subset of the syndrome but may potentially attend any cause of glucocorticoid excess.

Adrenal Cortex Function Tests↗