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Biomedical subjects

R M Galbraith

Publications and source records attributed to R M Galbraith.

At least 91 records · Page 5Linked to original sources
PubMed1979

Demonstration of alpha 1-antitrypsin by immunofluorescence on paraffin-embedded hepatic and pancreatic tissue.

Studies were performed in an attempt to improve current immunohistological techniques for the demonstration of alpha 1-antitrypsin (A1AT) in formalin-fixed paraffin-embedded tissues. The unwanted fluorescence (UF) commonly occurring in such procedures was found to be effectively eliminated by immunoadsorption of A1AT antisera with human serum lacking A1AT (Pi-null phenotype) coupled in solid phase to glutaraldehyde-activated aminohexyl-Sepharose 4B. Specificity of the antisera for A1AT was established by subsequent solid phase immunoadsorption against normal human serum bound to AH-Sepharose 4B. Using these techniques, immunoreactive A1AT was demonstrated in the cytoplasm of hepatocytes in liver biopsies obtained from patients with Z and MZ serum phenotypes, and in the cytoplasm of normal pancreatic islet cells.

Animals↗
PubMed1978

Detection of H-Y antigen by fluorescence microscopy.

A rapid and reproducible fluorescence microscopic technique has been devised to demonstrate H-Y antigen on membranes of human peripheral blood mononuclear cells. In 11 male subjects, 20 to 32% of mononuclear cells were positive for H-Y antigen, whereas less than 1% of such cells from 6 female donors were seen to be stained.

Animals↗
PubMed1978

Rheumatic disorders in primary biliary cirrhosis.

Eighty-three patients with primary biliary cirrhosis were investigated to determine the prevalence of rheumatic disorders. 14 had scleroderma, which tended to be mild but in several patients produced severe systemic manifestations. The CRST syndrome (calcinosis, Raynaud's phenomenon, sclerodactyly, telangiectasia) was only identified twice. There was an increased incidence of HLA A1+B8 in those patients with scleroderma. As well as those with scleroderma, 4 patients had a destructive arthropathy resembling avascular necrosis. 4 patients had an inflammatory arthritis, without specific features, but the frequency was no greater than might be expected in the general population.

Adult↗
PubMed1978

A new allele of human alpha1-antitrypsin: PiNhampton.

A new allele of alpha1AT is described. By isoelectric focusing, the microheterogeneous pattern of the variant was similar to but more cathodal than that of Pi N. This allele has therefore been tentatively designated PiNhampton(Nham). Further examination revealed that the minor bands of Nham are indistinguishable from the major bands of Z by isoelectric focusing, and a careful family study was necessary to clearly define the proband's phenotype. Pi Nham was found in association with M1, S, and Z, but to date its possession is not apparently related to clinical disorders or reduced serum levels of alpha1AT.

Adult↗
PubMed1978

A practical method for quantitation of antibody responses to tetanus and diphtheria toxoids in normal young children.

Antibodies to diphtheria and tetanus toxoids were assayed in 46 children from 16 to 33 months of age following vaccination. A reversed rocket immunoelectrophoretic technique was used for antibody determination. This method is simple and consistent, and although the limit of detection for antibodies of both types (about 1 U/ml) is above the normal range for primary immune responses, antibody levels in immunized children five weeks after a second injection of vaccine were within measureable range in all but two of the children studied. Levels more than one standard deviation above the mean were found in one child for both antitetanus and anti-diphtheria and in four children for anti-tetanus toxoid antibody only. All four of the high responders to tetanus toxoid were Black, carrying both Black and Caucasian Gm haplotypes. The two apparent nonresponders were Caucasian. All children had normal immunoglobulin levels, except for one with low IgA, who showed normal antibody responses to both toxoids. The results suggest that measurements of precipitating antibodies to diphtheria and tetanus toxoids provide a practical index of humoral immune function in small children.

Antibodies, Viral↗
PubMed1977

Lymphocyte culture: induction of colonies by conditioned medium from human lymphoid cell lines.

The presence of phytohemagglutinin or pokeweed mitogen in cultures of human peripheral blood mononuclear cells in agar is known to stimulate the formation of lymphoid colonies. We now report that similar colonies can be induced in the absence of plant lectins upon addition of filtered and ultracentrifuged conditioned medium (CM) obtained from certain human lymphoblastoid cell lines. Colony formation required at least 6 X 10(5) mononuclear cells per milliliter, and optimum results were obtained at concentrations of 1 X 10(6) cells/ml in the presence of 20% CM (50-500 colonies per 10(6) cells cultured). Individual cells within colonies displayed uniform morphological characteristics of lymphoid cells, and the majority formed rosettes with sheep erythrocytes, suggesting that they were of T-cell type.

Cell Count↗
PubMed1977

Increased frequency of the MZ phenotype of alpha-1-protease inhibitor in juvenile chronic polyarthritis.

Pi phenotypes of alpha-1-protease inhibitor were determined by isoelectric focusing and print immunofixation in 96 English children suffering from juvenile chronic polyarthritis. A significantly increased frequency of the MZ phenotype (10.41%) was found in comparison with a geographically matched control population (1.6%). The results of this study suggest that the possession of a Z-deficient allele of alpha-1-protease inhibitor could be a predisposing, aggravating, or perpetuating factor in the articular damage occurring in juvenile chronic polyarthritis.

Adolescent↗
PubMed1976

Immune response to HBsAg and the spectrum of liver lesions in HBsAg-positive patients with chronic renal disease.

Evidence of chronic hepatitis was found on histological examination in nine out of 15 patients positive for hepatitis-B surface antigen (HBsAg) who had either chronic renal failure or a functioning renal transplant. Cirrhosis had already developed in three of the patients, who deteriorated rapidly and died. Liver biopsies from the remaining 12 patients showed the features of chronic aggressive hepatitis in two, chronic persistent hepatitis in four, and minor histological lesions in six. The persistence of HBsAg in patients with renal failure or in those receiving immunosuppressive drugs after a transplant must indicate some impairment of the normal immune response to hepatitis-B viral antigens. Nevertheless, cellular or humoral immunity to HBsAg was detected in all eight patients with chronic hepatitis tested compared with only one out of five with minimal liver lesions, which suggests that the severity of the liver damage may be directly related to the degree of immunocompetence.

Adult↗
PubMed1976

Enhanced antibody responses in active chronic hepatitis: relation to HLA-B8 and HLA-B12 and porto-systemic shunting.

Titres of antibodies to rubella, measles, smooth muscle, nuclei, and Escherichia coli were examined in relation to the presence of particular histocompatibility antigens in 57 patients with active chronic hepatitis, 8 of whom were HBsAg positive. With the exception of antibodies to E. Coli, the HBsAg-negative patients with HLA-B8 or HLA-B12 had higher titres than those with neither, and antibody titres were highest in the 7 cases with both these histocompatibility antigens. In contrast, E. coli antibody titres were not related to the presence of particular histocompatibility antigens but correlated closely with the degree of portosystemic shunting. None of the HBsAg-positive patients possessed HLA-B8, and titres of all the antibodies were significantly lower than in the HBsAg-negative cases. The increased antibody response in HBsAg-negative patients is likely to be due to a genetically determined increase in immunological responsiveness for which HLA-B8 and HLA-B12 are markers. The results obtained in healthy family members also suggest that this defect in immunoregulation is under polygenic control.

Antibodies↗
PubMed1976

Detection of HBSAG in fixed liver tissue - use of a modified immunofluorescent technique and comparison with histochemical methods.

A modified immunofluorescent technique was used for the detection of HBSAg in formalin-fixed liver tissue, thereby allowing retrospective examination of paraffin sections and avoiding the need to split the sample at the time of biopsy. Comparison with two other methods, involving either orcein staining or standard haematoxylin and eosin (H and E) preparation for ground glass hepatocytes, showed slightly fewer positive hepatocytes in individual biopsies with the latter stain, but the specificity of both methods was high. In a series of 146 seropositive and 74 seronegative patients with a variety of liver disorders, hepatocytes positive for HBSAg were found in only one of 55 patients with acute hepatitis type B, whereas large numbers of positive cells were seen in all 22 healthy carriers of the surface antigen. In the 69 patients with chronic persistent or chronic aggressive hepatitis, the frequency of positive biopsies was 86% and 85% respectively. The positive cells in these cases were, in comparison with healthy carriers of HBSAg, much fewer in number and were scattered in random fashion throughout the lobule rather than occurring in discrete clumps or sheets. This variation in the intrahepatic expression of HBSAg may reflect differences in the immune response to hepatitis B viral antigens.

Acute Disease↗
PubMed1975

Chronic liver disease developing after outbreak of HBsAG-negative hepatitis in haemodialysis unit.

Chronic liver disease developing after acute hepatitis type B is well documented, but is not thought to occur after acute hepatitis due to other viruses. However, follow-up of 29 patients in a haemodialysis unit who contracted HBsAg-negative acute hepatitis during 1968-70 revealed 8 cases with raised serum-aminotransferase levels dating from that time. Liver biopsy in 7 of these disclosed chronic aggressive hepatitis in 3, of whom 2 had already progressed to advanced cirrhosis. Chronic persistent hepatitis was present in 2 others, and the remaining 2 had non-specific hepatitis in association with massive iron overload. Immunological studies demonstrated a higher frequency of cellular immunity to HBsAg in those who had previously had acute hepatitis than in those who had not, although the prevalence of humoral antibody was similar in the two groups. One possible explanation for these findings is the presence of immunological cross-reaction at a cellular level between the hepatitis B virus and that responsible for the initial outbreak.

Adult↗
PubMed1975

e Antigen-antibody system as indicator of liver damage in patients with hepatitis-B antigen.

The clinical relevance of the e antigen-antibody system was investigated in 61 people persistently positive for hepatitis-B surface antigen, including 22 healthy carriers. The e antigen was not detectable in any of the healthy carriers, whereas it was found in 15 out of 28 patients with chronic aggressive hepatitis and two out of 11 with chronic persistent hepatitis. Its presence therefore indicates chronic liver disease but its absence does not exclude it. It may prove to be a particularly useful prognostic aid in chronic persistent hepatitis, since one of the two patients in whom it was found later developed aggressive hepatitis. In contrast, e antibody is of little diagnostic help, for, though it was found mostly in healthy carriers (18;82%), it was also detectable in 9 (23%) of the patients with chronic hepatitis. In 13 (76%) of the patients positive for e antigen Dane particles were seen on electron microscopy, but these were also present in 5 (19%) of the patients positive for e antibody. These findings are consistent with other evidence suggesting that e antigen is not a surface component of the Dane particle, but rather an independent soluble protein manufactured by the host in response to infection with the hepatitis-B virus.

Antigens↗
PubMed1975

Fulminant hepatic failure in leukaemia and choriocarcinoma related to withdrawal of cytotoxic drug therapy.

In three patients with malignant disease HBsAg was detected in the serum at least 6 months before the development of acute hepatitis type B, which in each case followed a fulminant course to death. It is suggested that suppression of the normal immunological responses to hepatitis-B viral antigens by cytotoxic drug therapy permitted widespread infection of hepatocytes. Subsequently, upon withdrawal of these drugs, recovery of immunocompetence resulted in rapid destruction of all infected hepatocytes and massive liver damage. Screening for HBsAg before cytotoxic drug therapy, careful monitoring of liver function during its withdrawal, and prompt treatment with corticosteroids should abnormalities occur may prevent this unfortunate sequence of events.

Adult↗
PubMed1975

Cellular and humoral immunity to hepatitis-B surface antigen in active chronic hepatitis.

The hepatitis-B surface antigen (HBsAG) may be persistently present in the serum in a few cases of active chronic hepatitis but the cause of the disease in most patients is unknown. In a study of 39 HBsAg-negative cases cell-mediated immunity to HBsAg was observed in 24 (62%), suggesting a high frequency of previous infection with the hepatitis-B virus. Hepatitis-B surface antibody was detectable by radioimmunoassay in six patients, in all of whom complexes of HBsAg were present in the serum on electron microscopy. Out of 12 patients with HBsAg-positive active chronic hepatitis who were also studied eight, including all those untreated at the time, showed a cellular response to the antigen. Evidence of sensitization to a liver-specific cell surface lipoprotein was found with similar frequency in the two groups. These results are consistent with the hypothesis that hepatitis-B virus infection is important in initiating the disease in many cases of active chronic hepatitis and that sensitization to the liver cell membrane antigen is the autoimmune process responsible for the perpetuation of the liver injury.

Antibodies, Viral↗
PubMed1974

Histocompatibility antigens in active chronic hepatitis and primary biliary cirrhosis.

The frequency of antigens HL-A 1 (48%) and HL-A 8 (52%) in 54 patients with active chronic hepatitis from south-east England was significantly higher than in 89 control subjects from the same region (22% and 17% respectively). No correlation could be detected with the age and sex of the patients or with the presence of a particular immunological abnormality but the frequency of HL-A 1 and HL-A 8 was much lower in the nine patients who were positive for HBAg than in the 45 HBAg-negative cases. These results provide further evidence of the importance of genetic factors in active chronic hepatitis. In contrast the frequency of HL-A 1 and HL-A 8 in primary biliary cirrhosis, both in 45 patients from south-east England and in 28 patients from western Scotland, was not significantly different from that found in control groups from the same regions.

Age Factors↗