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R M Galbraith

Publications and source records attributed to R M Galbraith.

102 records · Page 6Linked to original sources
PubMedDate not supplied

Decreased serum group-specific component protein levels and complexes with actin in fulminant hepatic necrosis.

Monomeric G-actin has recently been shown to form high-affinity complexes with group-specific component protein (Gc), and this process might be expected to occur in vivo when hepatocyte necrosis with release of actin takes place. We therefore measured serum Gc levels and searched for evidence of actin-containing complexes of Gc in 147 sera from 21 normal subjects and 126 patients with acute and chronic liver diseases. Sera were examined for Gc concentration using an ELISA with purified Gc as standard. Gc levels were greatly diminished (less than 10 mg per dl) in 5 of 37 patients with acute hepatitis and 1 of 3 patients with subacute hepatic necrosis, and the mean values for these groups overall as well as those for chronic active hepatitis patients were significantly less than that observed in the normal controls (mean, 35.5 mg per dl). No significant alteration in Gc level was observed in the chronic disease categories studied. In contrast, Gc concentrations less than 10 mg per dl were found in 12 of 14 patients with fulminant hepatic necrosis, and the mean for this group (9.7) was significantly reduced (p less than 0.001). Sequential studies in 12 patients with acute hepatitis of moderate to marked severity but without a fulminant phase showed significant diminutions in initial Gc levels when these were compared with Gc levels obtained during recovery. Using analytical isoelectric focusing with print immunofixation, variable amounts of Gc:G-actin complexes could be demonstrated in virtually all sera examined, but the proportion of total Gc present as complex with G-actin appeared greater in fulminant hepatic necrosis sera.(ABSTRACT TRUNCATED AT 250 WORDS)

Actins↗
PubMedDate not supplied

Diminished serum Gc (vitamin D-binding protein) levels and increased Gc:G-actin complexes in a hamster model of fulminant hepatic necrosis.

Evidence for increased plasma levels of complexes containing Gc (vitamin D-binding protein) and cellular actin has been previously reported during fulminant hepatic necrosis in man. In order to study this process in more detail, we produced liver injury in hamsters using increasing doses of acetaminophen, with serial collection of sera for up to 168 hr after acetaminophen injection. Hamster Gc was purified using a three-step procedure and was shown to resemble closely human Gc. Polyclonal antihamster Gc was prepared and used in rocket immunoelectrophoresis and radial immunodiffusion studies for quantitation of total serum Gc and the percentage of Gc complexed with actin. Serum Gc levels were depressed in animals having liver damage, and the extent of depression 42 hr after acetaminophen correlated with the extent of elevation of AST. The proportion of the total Gc that was present in the complexed form increased in relation to the severity of the liver disease. In serial studies, diminution in Gc level preceded the rise in AST and increase in the percent complexed. These changes closely resemble observations in man and suggest that the hamster-acetaminophen hepatotoxicity model may be of value in further study of interactions of Gc with intracellular actin components and its role in actin homeostasis in conditions of massive tissue necrosis.

Acetaminophen↗
PubMedDate not supplied

Antibodies to polymerized human serum albumin in acute and chronic liver disease.

Since antibodies to polyalbumin have been noted to occur in patients with hepatitis or cirrhosis, we investigated sera from 219 patients with a variety of acute and chronic liver diseases with and without HBsAg using an ELISA. The prevalence of circulating polyalbumin antibodies was shown to be significantly increased over that of healthy controls (6.7%) in patients with autoimmune chronic active hepatitis (67%), acute viral hepatitis (41%) and fulminant hepatic necrosis (38%), but such antibodies were absent in chronic hepatitis B patients and other liver diseases. Serial studies in acute hepatitis showed evidence of antibodies early in the course of illness with disappearance prior to full recovery. In acute hepatitis B, the presence of polyalbumin antibodies was significantly associated with female sex (p less than 0.01), 3-fold higher transaminase levels and shorter duration of clinical illness (less than 4 weeks in all cases). Polyalbumin antibodies appear to be associated with diseases characterized by active hepatocyte necrosis. Since they are evident early in acute hepatitis B when complexes of polyalbumin and virus are likely, these antibodies may play an adjunctive role to other hepatitis B-related antibodies in the clearance of hepatitis B virus infection.

Antibodies↗
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Immunological studies of transferrin and transferrin receptors of human placental trophoblast.

In primate pregnancy, fetal iron is derived from maternal transferrin; however, the mechanisms by which iron is taken up by the human placenta have not yet been established. In the present study, transferrin was demonstrated on the microvillous surface of human trophoblast in immunohistological studies of 130 mature and immature placentae from both normal and abnormal pregnancies. Similar results were found for baboon placentae. Upon short-term culture of placental tissue, the amount of trophoblast transferrin decreased and no incorporation of 14C lysine into transferrin could be detected by radioimmunoelectrophoresis. Thus this transferrin apparently was not synthesized by the placenta. When transferrin was removed from cryostat sections of placenta by treatment with chaotropic agents, subsequently added transferrin bound in an identical distribution. The specificity of this reaction was confirmed by the lack of binding of other serum proteins and by displacement procedures in which trophoblast transferrin was shown to be dislodged by transferrin added in vitro. These findings suggest that placental iron transport is predicated by binding of transferrin to specific receptors on trophoblast.

Animals↗
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Native alpha 2-macroglobulin binds to a surface component of human placental trophoblast.

Immunofluorescence and radiobinding studies have shown that native human alpha 2-macroglobulin (alpha 2M), but not alpha 2M-trypsin complexes, binds to isolated human placental syncytiotrophoblast microvillous plasma membrane vesicles. Inhibition studies have indicated that alpha 2M may bind to a trophoblast surface protease. This interaction is of significance for the control of trophoblast invasiveness and haemostasis within the placental bed.

Cell Membrane↗
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Linkage between surface immunoglobulin and cytoskeleton of B lymphocytes may involve Gc protein.

The membrane immunoglobulin (MIg) of B lymphocytes is thought to have an important role in antigen recognition and cellular activation. In common with many membrane glycoproteins, MIg moves extensively in the lipid bilayer, and after binding of specific antisera displays lateral mobility with patch and cap formation. This phenomenon appears to involve the cytoskeleton, particularly the actin that is present in the cell membrane of B lymphocytes and aggregates beneath capped immunoglobulin. Recently, it has been reported that the isolation of MIg results in co-purification of actin and an unknown protein of molecular weight (MW) approximately 56,000 (refs 7, 8). We now demonstrate that this component displays physicochemical and immunological properties indistinguishable from those of Gc (group-specific component). In addition, evidence is presented which suggests that this vitamin D3-binding protein is involved in the linkage between MIg and actin, and may therefore be important in signal transduction.

Actins↗
PubMedDate not supplied

Studies of the normal human placental syncytiotrophoblast membrane: a combined immunological and physiochemical approach.

In view of the importance of the syncytiotrophoblast in the immunobiology of human pregnancy, the composition of this interface between fetus and mother was further studied by a combination of physicochemical and immunological approaches. Trophoblast membranes were solubilized using three classes of detergents: zwitterionic (sulfobetaine14), non-ionic (Triton X-100), and anionic (deoxycholate). Quantitative studies of protein released demonstrated the importance of dispersion of membranes into detergent, and optimum solubilization was then obtained at detergent:protein ratios of 1.3:1 for sulfobetaine, 2.5:1 for Triton X-100, and 4.4:1 for deoxycholate. Analysis of chaotrope-treated detergent-solubilized membrane components was performed by preparative isoelectric focusing followed by combined physiocochemical and immunological methods. The results revealed three major proteins which were identified as placental alkaline phosphatase, albumin, and transferrin. Certain additional low molecular weight proteins were also evident; one of these components displayed physicochemical properties similar to those of actin, but none appeared to be recognized by conventional heteroantisera raised to trophoblast membrane. These findings and the results of further immunological analysis by affinity chromatography are consistent with the concept that human trophoblast may express limited immunogenicity due in part to the presence of large amounts of absorbed maternal serum components and limited expression of fetal proteins.

Albumins↗
PubMedDate not supplied

Inhibition of lymphocyte activation by antisera to embryonic antigens shared with human placental trophoblast.

In order to further examine the inhibition of lymphocyte activation reported with conventional antisera to human trophoblast membranes, we studied their effects on cells stimulated by antigen in mixed lymphocyte culture (MLC) and by the mitogen phytohemagglutinin. The results were compared with the effects of antisera known to recognize intrinsic membrane determinants on activated T cells (DR antigens and placental alkaline phosphatase) and with those of antisera to normal human serum components such as transferrin which may bind to the activated lymphocyte membrane. The results indicated that antibodies to placental alkaline phosphatase, which constitutes the predominant specificity of conventional trophoblast membrane antisera, caused inhibition both of MLC response and, to a lesser extent, of activation induced by mitogen. Similar inhibition was obtained with antisera to human DR antigens, while antisera to normal human serum and transferrin were not suppressive. These findings, together with time course studies and immunocytochemical studies of the homologous antigens, suggest that these antisera mediate their inhibitory effects in part through binding to antigens which appear on cells as they undergo activation.

Alkaline Phosphatase↗
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Group specific component (Gc) and HIV diseases.

A previous report suggested a relationship between particular phenotypes of group specific component (Gc), and susceptibility or resistance to HIV infection, whereas other recent investigations failed to corroborate this finding. The present study demonstrated that Gc allele frequencies in white homosexual men corresponded to those expected, regardless of HIV serology and related disease. Assignment of phenotype was not influenced by Gc complexing secondary to tissue damage, or the process of infection per se. However, Gc allele frequencies in black patients with AIDS were significantly different from those in black control subjects, suggesting that the previously observed results might be in part explicable on the basis of gene admixture in ethnically mixed populations.

Acquired Immunodeficiency Syndrome↗
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Common variable immune deficiency syndrome associated with lupus anticoagulant.

A patient with an acquired immune deficiency syndrome developed a lupus anticoagulant in which the inhibitory activity was manifested only as a prolongation of the partial thromboplastin time. Contrary to previous reports, the substitution of platelets or platelet sonicates for phospholipid in this coagulant assay failed to correct the abnormality and the inhibitor did not exhibit immunoreactivity against phospholipids. The possible mechanisms of action of these inhibitors are discussed.

Adult↗