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Biomedical subjects

A J Kahn

Publications and source records attributed to A J Kahn.

At least 73 records · Page 4Linked to original sources
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↗
PubMed1982

A generational drift in rate of development of aversion to ethanol: associated shift in the sensitive period.

In prior studies with CF1 mice obtained from a commercial source, the development of aversion to ethanol was accelerated by providing 5% sucrose (w/v) as only liquid source during age 4 to 8 weeks, but not when pretreatment was begun at age 12 weeks. In repeat studies the effect was not found consistently. The data suggested that this was due to changes in timing of the sensitive period associated with differences in the rate of development of aversion to ethanol. To keep breeding and rearing conditions as constant as possible, a mating colony was started with mice obtained from the commercial source. Successive generations of this line were studied. A spontaneous drift in the rate of development of aversion to ethanol, with increasing rates in successive generations, was observed. The sensitive period for the effect of 5% sucrose on this parameter was at age 8 to 12 weeks in the earlier more slowly developing generations; and gradually shifted to 0 to 4 weeks in later generations with a more rapid development of aversion to ethanol.

Alcohol Drinking↗
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

Early membrane injury in lethally irradiated salivary gland cells.

The early manifestations of radiation injury in salivary glands were investigated in the rat. The animals received a single X-ray dose in the range of 200-2000 rad to their neck area. Glandular changes during the first 24 hours were studied by light and electron microscopy and by measuring serum amylase activity. The amount of cell necrosis was quantitated and expressed as necrosis index (NI), Parotid NI and serum amylase activity 24 hours following irradiation were directly proportional to the X-ray dose. The submandibular gland cells were radioresistant and so were the mucous cells of the sublingual gland. The major increase in parotid acinar cell necrosis occurred between 12 and 24 hours after irradiation. However, more than 100 per cent increase in serum amylase level was detected prior to the onset of any significant cell necrosis. As early as two hours following irradiation signs of cell membrane injury were demonstrable in the parotid by electron microscopy and consisted of intracellular oedema, sequestered degenerative cell membranes, and an accumulation of intramitochondrial particles. None of these changes was detectable in the submandibular gland. The implication of membrane injury in the lethal effects of radiation on parotid cells is discussed.

Amylases↗
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

Development of aversive behavior to ethanol in mice; alterability of the progression of this parameter.

The rate of development of aversion to ethanol was measured by the proportion of mice highly aversive to a 3% solution at age 24 weeks. Groups of C3H mice were exposed to either 0.5% or 5.0% ethanol during gestation or age 1 to 2 weeks, and for 1 week or 3 weeks at age 15 weeks. Male subjects only were studied. At age 24 weeks the groups exposed to 0.5% ethanol during gestation or age 1 to 2 weeks had significantly lower proportions of highly aversives to 3% ethanol than controls (38% and 46% versus 83%). Groups so exposed to 5.0% ethanol at an early age were not affected, nor were any group exposed to 0.5% or 5.0% ethanol at age 15 weeks. Groups of CF1 males were provided with 5.0% sucrose (w/v) as their only liquid source for one week beginning at age 4 weeks or 12 weeks. At age 24 weeks the group pretreated at age 4 weeks had a significantly greater proportion of subjects highly aversive to 3% ethanol than controls (63% versus 13%). The group pretreated at age 12 weeks was not significantly different from controls. Thus the rate of development of aversion to ethanol can be significantly decreased by exposure to 0.5% ethanol during a sensitive period, or significantly increased by exposure to 5% sucrose during a sensitive period.

Aging↗
PubMed1980

Normal osteoclast number and function in rat pups lacking parathyroid hormone.

In parathyroidectomized suckling rats, bone modeling and the number and activity of cells in the osteoclast population are normal. These findings are at variance with observations in older animals and suggest that factors other than parathyroid hormone influence osteoclast formation and function in the neonate.

Animals↗
PubMed1980

Successful bone-marrow transplantation for infantile malignant osteopetrosis.

A five-month-old girl with autosomal-recessive osteopetrosis received a bone-marrow transplant from her five-year-old HLA-MLC-identical brother after preparation with cyclophosphamide and modified total-body irradiation. Engraftment was documented by chromosomal analysis. Anemia, thrombocytopenia, and leukoerythroblastosis corrected within 12 weeks of transplantation. Low serum calcium and elevated serum alkaline and acid phosphatase levels became normal. Serial x-ray studies revealed bony remodeling and new nonsclerotic bone formation. A pretransplantation bone biopsy revealed small marrow spaces, rare marrow elements, increased osteoclasts, and no bony resorption. After transplantation, osteoclasts were actively resorbing bone, and medullary cavities contained normal bone marrow. Fluorescent Y-body analysis after transplantation revealed donor (male) osteoclasts and recipient (female) osteoblasts. Monocyte bactericidal activity, markedly decreased before transplantation, became normal. Vision, hearing, growth, and development were progressively improving 16 months after transplantation. Allogeneic bone-marrow transplantation appears to be the treatment of choice in this fatal disorder.

Blood Bactericidal Activity↗
PubMed1980

Intra-allantoic implantation: an alternative to the classical chorioallantoic membrane grafting technique.

A grafting method is described wherein donor tissue is partially inserted into a small slit cut into the proximal portion of the allantoic membrane of chick embryos aged 3.5-5.5 days. Cartilaginous bone rudiments handled in this manner readily vascularize, grow significantly, and begin osteogenesis within a 3-day incubation period. Compared to traditional chorioallantoic membrane grafting, usually done with hosts aged 9-12 days, the proposed intra-allantoic technique (1) greatly increased the period in which grafted materials are in residence (potentially up to 15 days) and (2) permits assessment of the host response of relatively young embryos.

Allantois↗