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Biomedical subjects

R C Graham

Publications and source records attributed to R C Graham.

At least 55 records · Page 3Linked to original sources
PubMed1974

Fibrinogen Cleveland II. An abnormal fibrinogen with defective release of fibrinopeptide A.

An abnormal fibrinogen (fibrinogen Cleveland II) was detected in the plasma of a 23-yr-old white man with a mild bleeding diathesis. The one-stage prothrombin time, thrombin time, and Reptilase time were all prolonged. 16 of 24 tested relatives had the defect, which appeared to be transmitted as an autosomal dominant characteristic. The thrombin time of normal plasma was slightly inhibited by the proband's plasma. The abnormally long thrombin time of fibrinogen Cleveland II was partially corrected by addition of calcium ions. Fibrinogen Cleveland II was indistinguishable from normal fibrinogen by immunoelectrophoresis, DEAE-cellulose column chromatography, or polyacrylamide gel electrophoresis of reduced fibrinogen in sodium dodecyl sulfate. The major defect detected appeared to be impaired release of fibrinopeptide A when fibrinogen Cleveland II was incubated with thrombin. This defect was localized to the NH(2)-terminal disulfide knot portion of the molecule. An abnormality of polymerization of fibrin monomers was also present, but the abnormal fibrin demonstrated relatively normal crosslinking. Despite these defects, fibrinogen Cleveland II achieved a degree of coagulability similar to normal fibrinogen and appeared to incorporate some molecules of fibrin with intact fibrinopeptide A into the clot. The fibrin clot that was formed appeared to be abnormal by electron microscopy. These functional defects and other descriptive characteristics appear to distinguish fibrinogen Cleveland II from other inherited abnormal fibrinogens.

Adult↗
PubMed1974

Normal peritoneal lymphocytes: A population with increased capacity for endocytosis.

The existence of lymphocyte to macrophage transformation among normal peritoneal lymphocytes (NPLs) was considered. We described the conditions under which pinocytosis of the enzyme tracer horseradish peroxidase (HRP) and phagocytosis of latex particles by NPLs occurred and compared these data with results obtained with splenic lymphocytes (SpLs), a better characterized source of lymphocytes. In the presence of relatively large concentrations (200 mug/ml to 1 mg/ml) of HRP, at least three times as many NPLs took up the protein by pinocytosis as did corresponding SpLs. Also, on the average, NPLs took up about twice as much HRP per cell than did SpLs. The uptake was rapid, and pinocytotic vesicles containing HRP were seen as early as 15 minutes after exposure to the tracer in NPLs but not in SpLs. In contrast to peritoneal macrophages, NPLs retained HRP in a variety of cytoplasmic vesicles and vacuoles in relatively undegraded form for at least 24 hours. Finally, if NPLs, which were nonphagocytic when freshly isolated, were cultured for 24 hours, both erythrophagocytosis and phagocytosis of latex spheres were observed. The cells which had taken up the latex were nonadherent to plastic, resembled lymphocytes ultrastructurally and were peroxidase negative. We concluded that under these culture conditions, NPLs had not transformed into morphologic macrophages, but phagocytic lymphocytes.

Animals↗
PubMed1973

Peroxidase arthritis. 3. Sequential changes in cellular composition of the developing inflammatory infiltrate.

Repeated daily injections of horseradish peroxidase into rabbit knee joints lead to a characteristic sequence of cellular events. Early transient infiltration with polymorphonuclear leukocytes was followed by a progressive increase in the number of macrophages. This appeared to represent, at least in part, a consequence of increased emigration of monocytes. Subsequently, increasing numbers of lymphocytes appeared. Many of the lymphocytes had frequent cytoplasmic polyribosomes. By the eighth or ninth day, immunoblasts, plasmablasts and immature plasma cells were observed; cytochemical evidence of local specific antibody synthesis first was demonstrated in such cells at this stage. These results demonstrate the sequential cellular events in an immunologic inflammatory response to local antigen. Questions remain concerning the stimulus for early monocyte emigration and macrophage accumulation, and the site of initial sensitization of lymphocytes; these problems are discussed.

Animals↗
PubMed1972

Peroxidase arthritis. I. An immunologically mediated inflammatory response with ultrastructural cytochemical localization of antigen and specific antibody.

Synovitis was produced in rabbits by daily intra-articular injections of the heterologous antigen horseradish peroxidase. The resulting "peroxidase arthritis" resembled rheumatoid arthritis histologically. Many of the subsynovial plasma cells, plasmablasts and immunoblasts contained specific antibody to horseradish peroxidase; the remainder appeared to contain immunoglobulins of other specificities. Peroxidase arthritis has unique advantages for the study of the cellular and subcellular events in the pathogenesis of the local immune inflammatory response to heterologous antigen. Antigen and specific antibody can be localized precisely by ultrastructural cytochemical technics. The reaction can be terminated at any stage, permitting observation of the early events in its pathogenesis.

Albumins↗
PubMed1972

Peroxidase arthritis. II. Lymphoid cell-endothelial interactions during a developing immunologic inflammatory response.

The interaction of lymphoid cells with vascular endothelium was studied during the development of immunologic synovitis in response to repeated intraarticular injections of a heterologous protein antigen. Lymphoid cells emigrated in venules and small veins, both by penetrating the endothelial cytoplasm and by traversing intercellular junctions. Frequent endothelial mitoses were coincident with lymphoid cell emigration. Endothelial cells in the involved vessels increased in number and bulged prominently into the vascular lumen. Endothelial nuclei contained dispersed chromatin and prominent nucleoli; the cytoplasm contained many vacuoles and abundant polyribosomes and rough-surfaced endoplasmic reticulum. Intercellular junctions were numerous and complex. These phenomena were prominent in rabbits studied after 12 to 16 daily injections; they then receded, despite continued antigenic stimulation. In animals studied after 35 or 37 daily injections, the venules appeared relatively normal, and lymphoid cell emigration was observed infrequently. Growth of new vessels was prominent at this stage. The present data do not establish whether the endothelial changes were the cause or the result of lymphoid cell emigration, although the latter seems more likely. Further studies are needed to elucidate the exact nature of these interactions.

Animals↗
PubMed1971

Spectrum and possible mechanism of carrageenan cytotoxicity.

Carrageenan, a sulfated polygalactose which suppresses established delayed hypersensitivity in vivo, is shown to be cytotoxic to macrophages but not to lymphocytes in vitro. This cytotoxicity depends on the carrageenan concentration and degree of lysosomal differentiation but is independent of serum. Survival of macrophages in the presence of carrageenan can be enhanced temporarily by corticosteroids. Ultrastructural studies reveal that carrageenan is readily taken up by macrophages and stored in lysosomes, which subsequently swell and rupture, apparently resulting in cell death. The presence of corticosteroids temporarily retards lysosome swelling. It is suggested that carrageenan may exert its cytotoxic effect by causing osmotic rupture of lysosomes. The possible immunologic significance of these findings is discussed.

Animals↗