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Biomedical subjects

T S Edgington

Publications and source records attributed to T S Edgington.

At least 217 records · Page 12Linked to original sources

Determination of the von Willebrand's disease antigen (factor VIII-related antigen) in plasma by quantitative immunoelectrophoresis.

Measurement of the von Willebrand's disease antigen (factor viii-related antigen) has become an increasingly useful tool in the differential diagnosis of those disorders of hemostasis characterized by an abnormality of factor viii procoagulant activity. Optimal conditions for assay of the von Willebrand's disease antigen in plasma by the quantitive immunoelectrophoretic technique are described. Potential sources ofsystematic error have been evaluated and a dilution effect has been identified.

Animals↗

Laboratory tests for diagnosis of autoimmune diseases.

1. Antimitochondrial antibody titers of 1:160 are practically diagnostic of primary biliary cirrhosis [71]. Serum antimitochondrial antibody titers of less than 1:16 are seen in 10% of cases of primary biliary cirrhosis. The antimitochondrial antibodies are usually absent in jaundiced patients with extrahepatic obstruction, drug sensitivity, and viral hepatitis. 2. Anti-smooth-muscle antibodies are noted in the various autoimmune liver disorders, viral hepatitis, infectious mononucleosis, malignancy, and intrinsic bronchial asthma. The smooth muscle antibody test helps in the differential diagnosis of lupoid hepatitis vs. systemic lupus erythematosus. The anti-smooth-muscle antibodies are usually absent in systemic lupus erythematosus. 3. The antinuclear antibody is frequently positive in the autoimmune liver diseases. In cases of chronic aggressive hepatitis associated with a high titer of antinuclear antibody the prognosis is usually grave. 4. The presence of antimicrosomal liver and kidney antibody is indicative of chronic aggressive liver disease, which is different from the classic lupoid hepatitis [95, 97]. 5. Hepatitis-B-antigen assay should be performed routinely to exclude viral hepatitis, type B. Heterophile antibody tests should done when the possibility of infectious mononucleosis must be considered. 6. Serum immunoglobulin determinations are of secondary importance in the laboratory diagnosis of autoimmune liver disorders. There is usually a polyclonal elevation of the major immunoglobulin in most chronic parenchymal liver diseases[48].

Age Factors↗

Human T lymphocyte "E" rosette function. I. A process modulated by intracellular cyclic AMP.

The capacity of normal human T lymphocytes to form rosettes with sheep red blood cells can be inhibited by drugs or agents which induce elevations in intracellular levels of cyclic AMP. The effect is early in the presence of agents which elicit rapid elevations in intracellular cyclic AMP (isoproterenol, aminophylline) and occurs later in the presence of cholera toxin which induces a dalayed increase in endogenous cyclic AMP. Dibutyryl cyclic AMP is inhibitory, and the effects of dibutyryl cyclic AMP and the adenyl cyclase stimulators are potentiated by inhibition of phosphodiesterase. These data provide substantial evidence that elevation of intracellular cyclic AMP diminishes E rosette function of lymphocytes.

Aminophylline↗

The number of D and E regions in the fibrinogen molecule.

The regional structure of fibrinogen was considered in reference to the terminal plasmin-cleavage fragments, D and E. By two independent approaches, a yield of two D and two E fragments was determined and this established the presence of two D and two E regions in each fibrinogen molecule. Immunochemically, it was shown that the expression of native fibrinogen determinants by the D:E complex was fully reconstituted by an equimolar mixture of D and E fragments, while other recombinant ratios failed to yield optimal reconstitution. Utilizing the cleavage-associated neoantigen of fibrinogen, fg-D(neo), as a quantitative immunochemical marker, it was determined that complete digestion of fibrinogen by plasmin yielded two D fragments. Since the D:E complex appeared to consist of an equal number of D and E fragments, the presence of two E regions and two D regions in fibrinogen was indicated. In polyacrylamide gel electrophoresis, the linear relationship between the concentration of the D or E fragment and its densitometric area in the gel was utilized to quantitate the yield of D and E fragments in terminal digests. The yield of two D and two E fragments was demonstrated and it was also shown that the yield of fragments was independent of the plasmin concentration and of the length of exposure of the D and E fragments to the enzyme. Thus, it appears that fibrinogen is a highly symmetrical molecule consisting of two E regions as well as two D regions.

Densitometry↗

Glomerular complement components in human glomerulonephritis.

154 of 255 individual human renal biopsies studied by immunofluorescence contained varying combinations of immunoglobulins (Ig), complement (C) components C1q, C3, C4, C5, C6, C8, C3 proactivator (C3PA), and/or properdin. 10 patients had linear deposits of Ig in glomeruli characteristic of antiglomerular basement membrane (GBM) antibodies; nine patients had C3 deposits (minimal in three) with generally lesser amounts of C1q, C4, C5, C6, and/or C8. 118 of the patients had granular deposits of Ig, suggesting immune complex glomerulonephritis; 114 of these had deposits of C3, usually accompanied by C1q, C4, C5, and/or C6. These observations indicate that the entire C sequence is deposited in glomeruli in most Ig-mediated glomerulonephritides. However, certain cases of anti-GBM glomerulonephritis with few or no C deposits may utilize pathways of injury independent of C.21 patients had granular C3 deposits without detectable Ig. C5, C6, and C8 were present in the majority of these patients while C1q was absent and scant C4 was observed in only two patients. The presence of only late-acting C components in the absence of Ig, C1q, and C4 suggests selective, possible nonimmune activation of the alternate C pathway. Finally, five patients had granular deposits of C3, C5, C6, and/or C8 diffusely in all or most glomeruli with a lesser number of glomeruli having additional focal granular deposits of Ig, C1q, and C4. This observation suggests that at least two patterns of C activation can occur simulatenously, possibly triggered by antecedent immune complex deposition and then perpetuated by an as yet undetermined mechanism.

Adult↗

Factor VIII coagulant activity and factor VIII-like antigen: independent molecular entities.

Factor VIII coagulant activity (VIII(C)) and the von Willebrand's disease antigen (Factor VIII-like antigen, vW-Ag) are biologically linked, and it has been suggested that they reside on the same molecule. However, insolubilized human isoantibody to VIII(C) and rabbit antiserum containing antibodies to VIII(C) and vW-Ag differentially bind and remove these entities from plasma, thus physically segregating one from the other. These findings indicate that Factor VIII coagulant activity resides on a molecule distinct from that expressing the von Willebrand's antigen.

Antigen-Antibody Reactions↗

Discriminating neoantigenic differences between fibrinogen and fibrin derivatives.

Discrimination between the physiological cleavage fragments of fibrinogen and fibrin offers an approach to differentiation between fibrinogenolytic processes and fibrinolysis after coagulation. By use of the cleavage-associated neoantigen of fibrinogen (fg-D(neo)) as a molecular marker, characteristic differences between the D regions of fibrinogen derivatives and fibrin derivatives can be demonstrated. The expression of fg-D(neo) by X, Y, D:E complex, and D-fragments of fibrinogen or fibrin is shown to be quantitative and unitary. Characteristic differences between fg-D(neo) sites present on fibrinogen cleavage fragments, as contrasted to fibrin cleavage fragments, are indicated by different competitive inhibition slopes, and appear to reflect differential binding affinity of selected anti-fg-D(neo) antibodies for the specific molecular site. There is a linear relationship between the slope of quantitative competitive inhibition and the relative molar ratio of fibrinogen and fibrin derivatives. Identical immunochemical expressions are observed in vitro and in vivo, and support the thesis that cleavage in vivo is produced by plasmin. The differential immunochemical features of fg-D(neo) expression may be the result of stable conformational and/or subtle structural differences between the D region of fibrinogen and fibrin cleavage fragments and suggest that precise changes in the D region are associated with the fibrin transition. These molecular features not only provide additional insight into the molecular immunology and structure of fibrinogen, but also appear to offer a new molecular approach to discrimination between fibrinogenolytic mechanisms as contrasted to fibrinolysis secondary to coagulation.

Abruptio Placentae↗

Immunobiology of fibrinogen. Emergence of neoantigenic expressions during physiologic cleavage in vitro and in vivo.

Physiological degradation of fibrinogen by plasmin leads to a recognized series of intermediate and stable terminal cleavage fragments and is associated with complex modulation and progressive loss of native antigenic expressions. Early in association with progressive plasmin cleavage, a stable cleavage-associated neoantigen, present in the D-fragment region of the molecule, is exposed in vitro and can be recognized by competitive inhibition radioimmunoassay with specific antiserum. It is demonstrated that there is an approximate equimolar expression of the cleavage-associated neoantigen. fg-D(neo), on the X-, Y-, and D-fragments and no recognizable (< 10(-3)) expression by fibrinogen or by the E-fragment. The X-fragment contains two D regions in respect to total D-fragment-associated antigenic expressions but unitary expression of fg-D(neo) is observed. The Y-fragment appears to contain one D-fragment region in respect to total D-fragment-associated antigens and exhibits close to unitary expression of fg-D(neo). Terminal cleavage digests containing the D- and E-fragments exhibit more than 10-fold greater native fibrinogen antigenic expression than the sum of the constituent fragments. This suggests the presence of a non-covalently associated native complex of the D- and E-fragments, and implies contiguity of the D- and E-fragments in the native fibrinogen molecule. The cleavage-associated neoantigen, fg-D(neo), is also generated in vivo and is generically demonstrable in the plasma of patients with various forms of in vivo fibrinolysis. These studies offer a precise immunochemical system, based upon defined molecular events, for the investigation of physiological and pathophysiological cleavage of fibrinogen. By contrast with other approaches to the assay of in vitro or in vivo cleavage of fibrinogen, assay of the cleavage-associated neoantigen fg-D(neo) is specific, sensitive, directly yields the molar concentration of all cleavage fragments except E, and is directly applicable to plasma.

Animals↗