Search PubMed⌕ Search

Biomedical subjects

A Horwitz

Publications and source records attributed to A Horwitz.

At least 37 records · Page 2Linked to original sources
PubMed1986

Phosphorylation of the fibronectin receptor complex in cells transformed by oncogenes that encode tyrosine kinases.

The fibronectin (FN) receptor in avian cells has been characterized previously as a complex of three membrane glycoproteins of about Mr 160,000, Mr 140,000, and Mr 120,000 (simply termed protein band 1, band 2, and band 3, respectively). Monoclonal antibodies to the band 3 protein of the complex prevent FN and laminin binding both in vivo and in vitro and enable the detection of the receptor proteins in the plasma membrane and in adhesion plaques. Association of the FN receptor proteins with the adhesion-plaque protein talin also has been reported. We now find that the band 2 and band 3 proteins in the complex are phosphorylated in Rous sarcoma virus-transformed chicken cells but not in normal chicken cells. Phosphorylation occurs predominantly on tyrosine and is accompanied by a reorganization of the receptor complex in the membrane of the transformed cells. Whereas normal cells contain the FN receptor in focal contacts and cellular processes between cells, v-src-transformed cells exhibit a more diffuse distribution of this receptor. In addition to the viral v-src oncogene, cells transformed by other avian oncogenes that also encode tyrosine kinases (v-fps, v-erbB, and v-yes) also express the receptor complex proteins in the phosphorylated state regardless of whether the transforming protein is detectable in adhesion plaques. These results suggest that the altered FN and laminin receptor proteins may contribute to the transformed phenotype, but their significance and role in the transformed state remain to be established.

Animals↗
PubMed1986

An application of three deviance theories to adolescent substance use.

This study tests the applicability of aspects of three theories of deviance--differential association, control, and strain--to the use of alcohol and drugs among a representative cross-section of 12-, 15-, and 18-year-olds. Regression analyses are conducted separately on each theory as well as on an overall model combining aspects of all three perspectives. Results show that differential association theory is a far more powerful predictor of adolescent alcohol and drug use than either the control or strain theories. The predictive power of the overall model is dependent upon the type of substance used as well as the age of the subject; however, the model is invariant between males and females.

Adolescent↗
PubMed1985

The cell substrate attachment (CSAT) antigen has properties of a receptor for laminin and fibronectin.

The cell substrate attachment (CSAT) antigen is an integral membrane glycoprotein complex that participates in the adhesion of cells to extracellular molecules. The CSAT monoclonal antibody, directed against this complex, inhibited adhesion of cardiac and tendon fibroblasts and skeletal myoblasts to both laminin and fibronectin, thus implicating the CSAT antigen in adhesion to these extracellular molecules. Equilibrium gel filtration was used to explore the hypothesis that the CSAT antigen functions as a cell surface receptor for both laminin and fibronectin. In this technique, designed for rapidly exchanging equilibria, the gel filtration column is pre-equilibrated with extracellular ligand to ensure receptor occupancy during its journey through the column. Both laminin and fibronectin formed complexes with the CSAT antigen. The association with laminin was inhibited by the CSAT monoclonal antibody; the associations with both fibronectin and laminin were inhibited by synthetic peptides containing the fibronectin cell-binding sequence. Estimates of the dissociation constants by equilibrium gel filtration agree well with those available from other measurements. This suggests that these associations are biologically significant. SDS PAGE showed that all three glycoproteins comprising the CSAT antigen were present in the antigen-ligand complexes. Gel filtration and velocity sedimentation were used to show that the three bands comprise and oligomeric complex, which provides an explanation for their functional association. The inhibition of adhesion by the CSAT monoclonal antibody and the association of the purified antigen with extracellular ligands are interpreted as strongly implicating the CSAT antigen as a receptor for both fibronectin and laminin and perhaps for other extracellular molecules as well.

Animals↗
PubMed1984

The kinetics of myoblast fusion.

The kinetics of myoblast fusion were estimated using two complementary assays. Both utilized suspensions of fusion-competent cells, i.e. 48-52-h cultures of chick pectoral muscle grown in a low-calcium medium, thus minimizing contributions arising from cellular migration. One assay, designed to measure the onset of membrane contiguity, relies on the transfer of a lipid dye, diI-C18-[3], from labelled to unlabelled cells. The other assay, designed to estimate the kinetics of appearance of morphologically distinct multinucleate cells in suspension (myoballs), relies on enzymic dissociation of cellular aggregates followed by nuclear staining. The assays demonstrate significant membrane contiguity within 20-30 min after initiating the fusion process; however, the multinucleate myoball morphology does not appear for at least one additional hour.

Animals↗
PubMed1984

Adhesive multiplicity in the interaction of embryonic fibroblasts and myoblasts with extracellular matrices.

Neff et al. (1982, J. Cell Biol., 95:654-666) have described a monoclonal antibody, CSAT, directed against a cell surface antigen that participates in the adhesion of skeletal muscle to extracellular matrices. We used the same antibody to compare and parse the determinants of adhesion and morphology on myogenic and fibrogenic cells. We report here that the antigen is present on skeletal and cardiac muscle and on tendon, skeletal, dermal, and cardiac fibroblasts; however, its contribution to their morphology and adhesion is different. The antibody produces large alterations in the morphology and adhesion of skeletal myoblasts and tendon fibroblasts; in contrast, its effects on the cardiac fibroblasts are not readily detected. The effects of CSAT on the other cell types, i.e., dermal and skeletal fibroblasts, cardiac muscle, 5-bromodeoxyuridine-treated skeletal muscle, lie between these extremes. The effects of CSAT on the skeletal myoblasts depends on the calcium concentration in the growth medium and on the culture age. We interpret these differential responses to CSAT as revealing differences in the adhesion of the various cells to extracellular matrices. This interpretation is supported by parallel studies using quantitative assays of cell-matrix adhesion. The likely origin of these adhesive differences is the progressive display of different kinds of adhesion-related molecules and their organizational complexes on increasingly adhesive cells. The antigen to which CSAT is directed is present on all of the above cells and thus appears to be a lowest common denominator of their adhesion to extracellular matrices.

Animals↗
PubMed1984

Separation of precursor myogenic and chondrogenic cells in early limb bud mesenchyme by a monoclonal antibody.

We have addressed the problem of the segregation of cell lineages during the development of cartilage and muscle in the chick limb bud. The following experiments demonstrate that early limb buds consist of at least two independent subpopulations of committed precursor cells--those in (a) the myogenic and (b) the chondrogenic lineage--which can be physically separated. Cells obtained from stage 20, 21, and 22 limb buds were cultured for 5 h in the presence of a monoclonal antibody that was originally isolated for its ability to detach preferentially myogenic cells from extracellular matrices. The detached limb bud cells were collected and replated in normal medium. Within 2 d nearly all of the replated cells had differentiated into myoblasts and myotubes; no chondroblasts differentiated in these cultures. In contrast, the original adherent population that remained after the antibody-induced detachment of the myogenic cells differentiated largely into cartilage and was devoid of muscle. Rearing the antibody-detached cells (i.e., replicating myogenic precursors and postmitotic myoblasts) in medium known to promote chondrogenesis did not induce these cells to chondrify. Conversely, rearing the attached precursor cells (i.e., chondrogenic precursors) in medium known to promote myogenesis did not induce these cells to undergo myogenesis. The definitive mononucleated myoblasts and multinucleated myotubes were identified by muscle-specific antibodies against light meromyosin or desmin, whereas the definitive chondroblasts were identified by a monoclonal antibody against the keratan sulfate chains of the cartilage-specific sulfated proteoglycan. These findings are interpreted as supporting the lineage hypothesis in which the differentiation program of a cell is determined by means of transit through compartments of a lineage.

Animals↗
PubMed1978

Congenital tyrosinemia.

Explore the source record for details and available documents.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

[Urological problems and genesis of the abdominal musculature aplasia syndrome].

Judging according to the frequent description of the syndrome of aplasia of the abdominal muscle above all in paediatric literature (up to now more than 250 cases), the knowledge of the symptomocomplex (aplasia of the abdominal muscle, malformations of the kidneys and the urinary tracts, cryptorchism) might be of particular interest for the urologist, since the urologic malformations decisively determine the prognosis quoad vitam of these patients. On the basis of three own cases the importance of the removal of infravesical obstruction is emphasized, whereas the reconstructive intervention for dilatation of upper urinary tracts is seldom mandatory.

Abdominal Muscles↗