Biomedical subjects

F Diaz-Gonzalez

Publications and source records attributed to F Diaz-Gonzalez.

5 recordsLinked to original sources

PubMed1997

Analysis of the tetraspanin CD9-integrin alphaIIbbeta3 (GPIIb-IIIa) complex in platelet membranes and transfected cells.

The platelet integrin, alphaIIbbeta3 (GPIIb-IIIa), and the tetraspanin, CD9, are integral membrane proteins that are abundant in platelet membranes. We have identified several proteins, including CD9, which were co-precipitated by anti-alphaIIbbeta3 antibody from untreated, resting platelets that were solubilized with the poly(oxyethylene) non-ionic detergent, Brij-35. Immunoblot and quantitative immunoprecipitation showed that the association of alphaIIbbeta3 with CD9 is specific and stoichiometric. The interaction between CD9 and alphaIIbbeta3 is probably hydrophobic, as Triton X-100 and hydrophobic detergents of the Brij series completely dissociated the CD9-alphaIIbbeta3 complex. Recombinant CD9 and alphaIIbbeta3 can associate after transfection into Chinese hamster ovary cells, as seen by co-immunoprecipitation and co-localization in the periphery of spreading cells and in the lamellipodia of cells plated on fibrinogen. This co-localization is absent from focal adhesions. Furthermore, anti-CD9-coated latex beads clustered alphaIIbbeta3 with CD9. This work indicates that the tetraspanin, CD9, is associated with beta3 integrins in resting platelets and transfected cells.

Animals↗

PubMed1996

Breaking the integrin hinge. A defined structural constraint regulates integrin signaling.

Integrins are heterodimeric (alpha, beta) cell adhesion receptors. We demonstrate that point mutations in the cytoplasmic domains of both the alpha and beta subunits promote constitutive signaling by the integrin alphaIIbbeta3. By generating charge reversal mutations, we show these "activating" mutations may act by disrupting a potential salt bridge between the membrane-proximal portions of the alpha and beta subunit cytoplasmic domains. Thus, the modulation of specific interactions between the alpha and beta subunit cytoplasmic domains may regulate transmembrane signaling through integrins. In addition, these activating mutations induce dominant alterations in cellular behavior, such as the assembly of the extracellular matrix. Consequently, somatic mutations in integrin cytoplasmic domains could have profound effects in vivo on integrin-dependent functions such as matrix assembly, cell migration, and anchorage-dependent cell growth and survival.

Amino Acid Sequence↗

PubMed1995

Beta 3 integrin-mediated fibrin clot retraction by nucleated cells: differing behavior of alpha IIb beta 3 and alpha v beta 3.

Fibrin clot retraction may be important in resolution of thrombi and, in platelets, is mediated by integrin alpha IIb beta 3 (GPIIb-IIIa). Nucleated cells that lack alpha IIb beta 3 can retract fibrin clots, and we now report that integrin alpha v beta 3 can support this process. In addition, we compared the capacities of recombinant beta 3 integrins to mediate clot retraction in Chinese hamster ovary and M21 melanoma cells. We found that alpha v beta 3, but not alpha IIb beta 3, could spontaneously support retraction. Transferring the cytoplasmic domain of alpha v to alpha IIb enabled the resulting chimeric alpha IIb beta 3 to support clot retraction. The capacity of the alpha v cytoplasmic domain to support clot retraction was not caused by activation of the ligand binding function of alpha IIb beta 3 or by enhancement of alpha IIb beta 3's capacity to stimulate the formation of focal adhesions or the tyrosine phosphorylation of pp125FAK. These experiments define requirements for alpha IIb beta 3-mediating clot retraction, establish the capacity of alpha v beta 3 to mediate this process, and suggest differing functional roles of the alpha v and alpha IIb cytoplasmic domains.

Animals↗

PubMed1994

Nontropical pyomyositis in adults.

Pyomyositis (PMS) is a primary infection of striated muscle. Recent scanty reports suggest that non-tropical PMS may differ from classical tropical PMS. To address this question, 12 cases of nontropical PMS seen at two hospitals between 1976 and 1992 were reviewed and an English-literature search of similar cases was conducted. Both the series and reported cases are pooled together and herein reported. The age distribution of the 97 patients showed 30-50 and 60-70-year peaks, with a 3:1 (male-female) ratio. Fever, high erythrocyte sedimentation rate, and muscle stiffness or inflammation were present in more than 75% of patients. Muscles of the thigh (54%), back (13%), buttock (11%), arm (9%), or chest wall (4%) were involved. Staphylococci (61%), gram-negative bacilli (16%), streptococci (12%), and fungi (2%) were isolated from muscle specimens. Human immunodeficiency virus infection, diabetes mellitus, hemopoietic disorders, and other conditions with defective neutrophil function were present in 64 patients (66%). Drainage of pus and antibiotic therapy were the standard treatments. The mortality rate reached 10%. Analysis of patients classified by the comorbid condition showed differences in age, causative microorganisms, clinical features, and death rate. It is concluded that several clinical presentations of nontropical PMS are at variance with that of tropical PMS.

Adult↗

PubMed1992

Increased binding of synovial T lymphocytes from rheumatoid arthritis to endothelial-leukocyte adhesion molecule-1 (ELAM-1) and vascular cell adhesion molecule-1 (VCAM-1).

The infiltration of the synovial membrane (SM) by mononuclear cells, mostly T cells, is a typical histopathological feature associated with rheumatoid arthritis (RA). The entry of T lymphocytes into the SM is believed to be mediated by a number of molecules in the endothelium that are induced in response to a series of inflammatory mediators. In this study, we have investigated the adhesion of synovial T cells from RA patients to two endothelial ligands: endothelial-leukocyte adhesion molecule-1 (ELAM-1), the only selectin known to function as a vascular addressin for T cells, and vascular cell adhesion molecule-1 (VCAM-1), the cellular ligand of VLA-4. Our results clearly demonstrate that synovial T cells isolated from both SM and synovial fluid (SF), bearing an activated and memory phenotype, displayed an enhanced capacity to interact with these two endothelial molecules as compared with T cells from peripheral blood (PB) either of the same RA patients or healthy donors. A further enhancement of VLA-4-mediated T cell binding to VCAM-1 and fibronectin could be observed when already in vivo-activated synovial T cells were stimulated in vitro with phorbol esters, suggesting the existence of several cellular affinity levels for both very late activation-4 (VLA-4) ligands. Moreover, both PB and synovial T cells from RA patients exhibited strong proliferative responses when they were cultured with either fibronectin or VCAM-1 in combination with submitogenic doses of anti-CD3 mAb. This increased endothelial binding ability of synovial T lymphocytes together with their proliferation in response to the interaction with VCAM-1 and fibronectin may represent important mechanisms in the regulation of T cell penetration and persistence in the chronically inflamed SM of RA.

Antigens, CD↗