Biomedical subjects

G Corson

Publications and source records attributed to G Corson.

3 recordsLinked to original sources

PubMed2001

Selective intracellular retention of extracellular matrix proteins and chaperones associated with pseudoachondroplasia.

Mutations in the cartilage oligomeric matrix protein (COMP) gene result in pseudoachondroplasia (PSACH), which is a chondrodysplasia characterized by early-onset osteoarthritis and short stature. COMP is a secreted pentameric glycoprotein that belongs to the thrombospondin family of proteins. We have identified a novel missense mutation which substitutes a glycine for an aspartic acid residue in the thrombospondin (TSP) type 3 calcium-binding domain of COMP in a patient diagnosed with PSACH. Immunohistochemistry and immunoelectron microscopy both show abnormal retention of COMP within characteristically enlarged rER inclusions of PSACH chondrocytes, as well as retention of fibromodulin, decorin and types IX, XI and XII collagen. Aggrecan and types II and VI collagen were not retained intracellularly within the same cells. In addition to selective extracellular matrix components, the chaperones HSP47, protein disulfide isomerase (PDI) and calnexin were localized at elevated levels within the rER vesicles of PSACH chondrocytes, suggesting that they may play a role in the cellular retention of mutant COMP molecules. Whether the aberrant rER inclusions in PSACH chondrocytes are a direct consequence of chaperone-mediated retention of mutant COMP or are otherwise due to selective intracellular protein interactions, which may in turn lead to aggregation within the rER, is unclear. However, our data demonstrate that retention of mutant COMP molecules results in the selective retention of ECM molecules and molecular chaperones, indicating the existence of distinct secretory pathways or ER-sorting mechanisms for matrix molecules, a process mediated by their association with various molecular chaperones.

Aggrecans↗

PubMed1994

Elastin exhibits a distinctive temporal and spatial pattern of distribution in the developing chick limb in association with the establishment of the cartilaginous skeleton.

In this work we have analyzed the presence of elastic components in the extracellular matrices of the developing chick leg bud. The distributions of elastin and fibrillin were studied immunohistochemically in whole-mount preparations using confocal laser microscopy. The association of these constituents of the elastic matrix with other components of the extracellular matrix was also studied, using several additional antibodies. Our results reveal the transient presence of an elastin-rich scaffold of extracellular matrix fibrillar material in association with the establishment of the cartilaginous skeleton of the leg bud. The scaffold consisted of elastin-positive fibers extending from the ectodermal surface of the limb to the central cartilage-forming regions and between adjacent cartilages. Fibrillin immunolabeling was negative in this fibrillar scaffold while other components of the extracellular matrix including: tenascin, laminin and collagens type I, type III and type VI; appeared codistributed with elastin in some regions of the scaffold. Progressive changes in the spatial pattern of distribution of the elastin-positive scaffold were detected in explant cultures in which one expects a modification in the mechanical stresses of the tissues related to growth. A scaffold of elastin comparable to that found in vivo was also observed in high-density micromass cultures of isolated limb mesodermal cells. In this case the elastic fibers are observed filling the spaces located between the cartilaginous nodules. The fibers become reoriented and attach to the ectodermal basal surface when an ectodermal fragment is located at the top of the growing micromass. Our results suggest that the formation of the cartilaginous skeleton of the limb involves the segregation of the undifferentiated limb mesenchyme into chondrogenic and elastogenic cell lineages. Further, a role for the elastic fiber scaffold in coordinating the size and the spatial location of the cartilaginous skeletal elements within the limb bud is also suggested from our observations.

Animals↗

PubMed1984

Identification and localization of creatine kinase B and M in normal, ischemic and necrotic myocardium. An immunohistochemical study.

We utilized immunoperoxidase methods to study the distribution of CK-B and CK-M in normal, ischemic and necrotic myocardium. Human myocardium was obtained from autopsy (n = 10) and surgery (n = 16). Cardiac tissue from 22 dogs with experimental myocardial infarction induced by closed-chest coronary balloon occlusion and four dogs with myocardial ischemia without necrosis induced by a 50% reduction in left main coronary artery blood flow for 3 h were studied. Duration of occlusion was 45 min (n = 2), 3 h (n = 8), 5 to 6 h (n = 7), 15 to 24 h (n = 5). Highly purified anti-CK-B and M were prepared in our laboratory and obtained commercially. In all cases, control experiments were performed. Microscopically normal human and dog myocardium uniformly stained for CK-B and CK-M. Necrotic myocardium from patients with acute infarcts (10 to 24 h old) showed markedly reduced immunostaining. In dogs with 3 to 24 h occlusion immunostaining was significantly reduced for both CK-B and CK-M in regions confirmed to be necrotic by triphenyl tetrazolium chloride (TTC) and H & E staining. Myocardial necrosis was confirmed in the 3-h infarcts by electron microscopy (EM). In the four dogs with a 50% reduction in left main flow for 3 h, ischemia was demonstrated by glycogen loss in periodic acid-Schiff stained-sections; but there was no evidence of necrosis by EM or TTC, and there was no loss of immunostaining evident for CK-B and CK-M. Thus, using immunoperoxidase techniques, CK-B and CK-M were visualized in normal and ischemic myocardium, with decreased staining in necrotic tissue. These findings indicate that cell death is necessary for the demonstration of CK-M and CK-B loss from the myocardium by this technique.

Animals↗