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Biomedical subjects

R N MacSween

Publications and source records attributed to R N MacSween.

At least 55 records · Page 3Linked to original sources

Correlation between high-molecular-weight Fc gamma-receptor-blocking factors in serum and renal allograft survival.

In this study, we have demonstrated the occurrence of IgG class noncytotoxic, lymphocyte Fc gamma-receptor-blocking antibodies in a proportion of sera obtained from transfused uremic patients. The presence of these antibodies was not found to correlate with subsequent renal allograft survival. Serum fractionation studies did however reveal a striking correlation between graft survival and Fc gamma-receptor blocking mediated by a serum factor(s) with a sedimentation coefficient of greater than 19S. The precise nature of this factor remains to be clarified.

Blood Proteins↗

Unusual variant of primary sclerosing cholangitis.

Two cases of primary sclerosing cholangitis are described, in which the characteristic bile duct lesions were unusual because there was an exuberant and exaggerated fibrous replacement of the ducts which produced dense fibrotic scars in portal tracts.

Adult↗

Expression of tissue polypeptide antigen (TPA) in fetal and adult liver: changes in liver disease.

The distribution of tissue polypeptide antigen (40 kD molecular weight) in normal adult and fetal liver, and in liver disease was investigated and compared with the distribution of low and high molecular weight cytokeratins. In normal liver tissue polypeptide antigen was found only in bile duct epithelium; this distribution is similar to that of high molecular weight cytokeratin, but differs from that of low molecular weight cytokeratins. In liver disease it was found in areas of ductular transformation; in Mallory's bodies; and in alcoholic liver disease and primary biliary cirrhosis in some hepatocytes that did not contain Mallory's bodies.

Adult↗

In vivo and in vitro blocking of human lymphocyte Fc gamma-receptors by intravenous gammaglobulin.

Lymphocyte subpopulations were measured in patients with idiopathic thrombocytopenic purpura before and immediately after high dose intravenous gammaglobulin (IV-IgG) therapy. A significant relative and absolute reduction in the Fc gamma-receptor bearing lymphocyte subpopulation was observed in 5 out of 7 patients tested. In vivo modulation of lymphocyte Fc gamma-receptors therefore probably occurs: an effect which may be attributable to the Fc gamma R-blocking anti-lymphocytic antibodies found in IV-IgG preparations. In vitro studies showed that IV-IgG preparations also contain antibodies with the capacity to block Fc gamma-receptors on human monocytes and polymorphs and that these antibodies can inhibit the T cell response to phytohaemagglutinin. These anti-lymphocyte antibodies may be important in the mode of action of high dose IV-IgG therapy.

Aged↗

Interstitial nephritis and primary biliary cirrhosis: a new association?

Interstitial nephritis may be associated with a variety of auto-immune disorders, but there have been no reports among these of primary biliary cirrhosis. A patient presenting with sodium- and potassium-losing nephropathy due to interstitial nephritis was discovered to have primary biliary cirrhosis which was asymptomatic. Correction of the electrolyte abnormalities with sodium and potassium supplements had no effect on renal function, but creatinine clearance increased from 28 to 68 ml/minute during a seven-week course of prednisolone. The occurrence in primary biliary cirrhosis of other forms of renal tubular dysfunction, the frequent presence in both interstitial nephritis and primary biliary cirrhosis of multi-system involvement and the close temporal relationship in this patient, suggest that the two conditions were related.

Biopsy↗

Desmin-containing stellate cells in rat liver; distribution in normal animals and response to experimental acute liver injury.

Using immunohistochemical methods, we have confirmed that the perisinusoidal cells in rat liver express the intermediate filament protein, desmin, and we have used this marker for identification of the cells on light microscopy. The study has been extended to quantify the response of perisinusoidal cells to acute liver injury induced by carbon tetrachloride. A significant increase in desmin-positive cells was observed in areas of necrosis as early as 48 h following the administration of a single bolus of carbon tetrachloride. This reached a peak at 72 h, with a five-fold increase in desmin-positive cells in areas of necrosis. These observations are consistent with the hypothesis that perisinusoidal cells are involved in the response to acute liver injury. Anti-desmin antibodies are of potential value in further characterizing the functional role of perisinusoidal cells in normal and diseased liver.

Animals↗

Hepatic vein lesions in alcoholic liver disease: retrospective biopsy and necropsy study.

Obliteration of the terminal hepatic venules with perivenular fibrosis (phlebosclerosis) is a well recognised feature in alcoholic liver disease. Veno-occlusive lesions with intimal obliteration of hepatic veins and a lymphocytic phlebitis of hepatic veins may also be present. We looked for these lesions in 256 liver biopsies and 50 livers obtained at necropsy from patients with alcoholic liver disease. Phlebosclerosis was a universal finding in alcoholic hepatitis and cirrhosis and showed increasing severity with progressive liver injury. Veno-occlusive lesions, however, were found in only 25 of 256 (9.8%) of biopsies and 11 of 50 (22%) of livers obtained at necropsy, showing alcoholic hepatitis or cirrhosis: lymphocytic phlebitis was found in 10 of 256 (3.9%) and two of 50 (4%), respectively. Moreover, veno-occlusive lesions were generally mild. The prevalence of veno-occlusive lesions and lymphocytic phlebitis was considerably less than has been previously documented. Phlebosclerosis may have a different mechanism and be a more important contributory factor in progressive liver injury.

Adult↗

Immunosuppression following alloantigen exposure: a role for lymphocyte Fc gamma-receptor blocking antibodies.

In this study we have shown that IgG class, noncytotoxic, Fc gamma-receptor blocking antilymphocyte antibodies can de detected in a high proportion of patients who have previously been exposed to alloantigens, i.e. multiple transfused uraemic patients, haemophiliacs and male homosexuals. These antilymphocyte antibodies appear to cross-react with human spermatozoa. Monomeric IgG preparations from these patients were also found to significantly impair T-cell responsiveness in vitro. Depression of cell mediated immunity by these antibodies may contribute to prolonged graft survival in uraemic patients but may also predispose to infection.

Acquired Immunodeficiency Syndrome↗

Transfusion-induced, Fc gamma-receptor-blocking antibodies: spectrum of cellular reactivity.

In this study we have shown that transfusion-induced Fc gamma R-blocking antibodies have the capacity to react with various cell types which are known to possess this receptor i.e., lymphocytes (T and B cells), polymorphs and platelets. In contrast we were unable to demonstrate any reactivity with K (or NK) lymphocytes or with monocytes. The spectrum of cellular reactivity exhibited by these antibodies suggests that their effect on the immune system may be complex.

Adolescent↗

Breast cancer in women with primary biliary cirrhosis.

The occurrence of extrahepatic malignancy was studied in 195 unselected patients who satisfied predetermined biochemical, immunological, and histological criteria for the diagnosis of primary biliary cirrhosis. The incidence of breast cancer in women with primary biliary cirrhosis was found to be significantly higher than in an age and sex matched control population from the same well defined geographical area (p less than 0.0015). The association of breast cancer and primary biliary cirrhosis remains unexplained, though diminished immunological surveillance, fat soluble vitamin deficiency, or endocrine dysfunction may play a part.

Aged↗

Biosynthesis of complement components by cultured rat hepatocytes.

Hepatocytes which had been isolated from the livers of Charles River rats were cultured in vitro. The cells were shown to synthesize albumin and the complement components C4, C2, C3 and B. Pulse-label studies with [35S]methionine showed that C4 and C3 were synthesized as single polypeptide chains. Pro-C4 did not appear to be converted into the plasma form of C4 intracellularly, whereas cell lysates contained the alpha- and beta-chains of plasma C3 as well as pro-C3. It is concluded that culture of rat hepatocytes in vitro provides a useful technique for studies of the synthesis of complement components.

Albumins↗

Isolation of labile Fcgamma-receptors from human peripheral blood lymphocytes and production of an antiserum.

In this study, we have isolated membranelabile Fcgamma-receptors (i.e. FcgammaR I) from normal human peripheral blood lymphocytes and have produced a rabbit antiserum to this protein. Using this antiserum, we have shown that membrane-labile and membrane-stable (i.e. FcgammaR II) Fcgamma-receptors are antigenically distinct and that these two forms of the receptors probably coexist on the same lymphocyte subpopulation. Moreover, it was apparent that lymphocyte FcgammaR Is are distinct from FcgammaRs expressed on other cell types (e.g. monocytes, polymorphs and spermatozoa). Preliminary evidence does suggest, however, that human platelets express an FcgammaR which is antigenically similar to human lymphocyte FcgammaR I.

Animals↗

Serum Fc gamma-receptor-like molecules in primary biliary cirrhosis: a possible immunoregulatory mechanism.

Functionally active Fc gamma-receptor-like molecules were isolated from normal human serum by affinity chromatography and shown to have an apparent molecular weight (MW) of approximately 60,000 as assessed by SDS-polyacrylamide gel electrophoresis. These low MW Fc gamma-receptor-like molecules were found to be significantly reduced in whole serum, and in all of six serum fractions, obtained from patients with primary biliary cirrhosis (PBC). A high MW IgG-binding factor, with partial Fc gamma-receptor-like activity, was also found in PBC serum. This factor was also observed to a lesser extent in normal serum. Detailed analysis of this factor suggests that it is a large macromolecule consisting of antigen (unknown). IgG class antibody and 60K Fc gamma-receptor-like molecules. Binding of serum Fc gamma R-like molecules to immune complexes may account for the apparent reduction in Fc gamma-receptor-like activity observed in whole PBC serum. These macromolecules may play an important role in immunoregulation.

Adult↗

Comparison of Fc gamma-receptors isolated from normal human serum and peripheral blood lymphocytes.

In this study, Fc gamma-receptors were isolated from normal human peripheral blood lymphocytes by prolonged incubation at 37 degrees C and purified by affinity chromatography using Sepharose 4B combined with heat-aggregated IgG. These labile Fc gamma R-receptors were shown to be functionally active with an apparent molecular weight of 60 K. Serum Fc gamma-receptor like molecules were also isolated and were shown to be of similar molecular weight. In addition, a high molecular weight (greater than 19S) serum IgG-binding protein was found. The basic sub-unit structure of this molecule was also 60K suggesting that the Fc gamma-receptor may exist in a polymeric or complexed form in normal human serum.

Humans↗