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Biomedical subjects

I R Mackay

Publications and source records attributed to I R Mackay.

At least 253 records · Page 14Linked to original sources
PubMed1983

Strain differences in mice in carbon tetrachloride-induced liver injury.

A study was made in inbred mice of genetic determinants of toxic liver cell injury, and the subsequent occurrence of autoantibodies to mouse liver-specific protein (M-LSP). Carbon tetrachloride was injected s.c. in sublethal doses to induce liver cell damage in 4 strains of mice, BALB/c, C3H, C57BL/6 and SJL/J. The degree of liver cell damage was assessed by blood cholylglycine levels and by semiquantitative histological analysis 1, 4, 7, 14, 21 and 45 days after dosing. Striking differences were observed among the 4 strains in degrees of liver necrosis, cellular infiltration and rate of removal of the necrotic tissue. BALB/c was the strain most susceptible to the necrotizing effects of CCl4. These mice showed confluent areas of hepatocellular necrosis from Day 1 and histological recovery was protracted up to 3 weeks, and was accompanied by pronounced macrophage activity and a cellular inflammatory response. Mice of the SJL/J strain were the least susceptible and showed minor hepatocellular necrosis, which resolved by Day 7, and a slight histiocytic response. C3H and C57BL/6 showed lesions which were intermediate between the other 2 strains. The autoantibody response to LSP was weak, transient and detected only in C57BL/6 mice. This study indicates the presence of genetic control, either H-2 or non-H-2 linked, over the degree of liver cell necrosis resulting from toxic liver injury, and the ensuing cellular infiltrate and rate of removal of the necrotic tissue.

Animals↗
PubMed1983

Association of increased immune complexes, platelet IgG and serum IgG in chronic active hepatitis.

Platelet associated IgG (PA-IgG), serum IgG and immune complexes (IC) were measured and correlated with the degree of thrombocytopenia in 32 patients with chronic active hepatitis (CAH), classified as of autoimmune type in 24 and cryptogenic in eight. Of the 32 patients, 24 had raised PA-IgG and 18 of these were thrombocytopenic (greater than 150 X 10(9) platelets/1); in only two thrombocytopenic patients was the level of PA-IgG not increased. Platelet counts showed a significant inverse logarithmic correlation with PA-IgG levels (r = 0.456, P less than 0.01). Twelve patients had raised levels in serum of ICs, 11 of these also had raised PA-IgG and 10 of these 11 were thrombocytopenic. Serum IgG was raised in 10 patients and correlated with PA-IgG (r = 0.489, P less than 0.01). Of the 24 patients with autoimmune CAH, 13 had low platelet counts and 10 had raised levels of PA-IgG whereas of the eight patients with cryptogenic CAH, seven had raised PA-IgG and all were thrombocytopenic. These results for patients with CAH show that raised levels of circulating ICs are associated both with thrombocytopenia and with raised PA-IgG, and support the hypothesis that serum IgG and/or ICs may influence amounts of PA-IgG.

Antigen-Antibody Complex↗
PubMed1982

Rapid replicate reverse haemolytic plaque assay directly in microwells used for tissue culture.

The reverse haemolytic plaque assay was adapted as a micromethod using microwells of flat-bottomed microtitre trays. To microwells containing the lymphocytes under test were added protein A-coupled ox erythrocytes, developing antisera directed against any class of immunoglobulin, and guinea pig complement absorbed with protein A-coupled erythrocytes. Plaques were scored by counting with a stereoscan microscope. The method is applicable both to spontaneous and mitogen-induced plaque formation and, as a further development of the technique to differentiated B cells in pokeweed mitogen-driven cultures, plaques were enumerated directly in the same wells of the microtitre tray as were employed for culture of the B cells. The method allows for several hundred plaque assays at one sitting.

Antibody-Producing Cells↗
PubMed1982

HLA and alcoholic cirrhosis.

In fifty-seven patients with alcoholic cirrhosis the frequency of HLA-DR2 was found to be 47.4%, in contrast to 26.1% in 119 normal subjects and 14.0% in 43 cases of autoimmune-type chronic active hepatitis (CAH). The frequencies of HLA-DR3 in the three respective groups also differed, being 24.6%, 31.9% and 74.4%. The greatly differing HLA-DR profiles in alcoholic cirrhosis and CAH point to immunogenetic differences in predisposition to these two liver diseases.

Autoimmune Diseases↗
PubMed1982

Use of tetanus toxoid for testing cell-mediated immunity.

Tetanus toxoid was assessed as a skin test antigen for the measurement of cutaneous delayed-type hypersensitivity (DTH) by comparing the responses to intradermal injections of aqueous tetanus toxoid and an extract of Candida albicans in 50 randomly selected healthy adults and 10 adults with immunodeficiency. Of 42 healthy subjects previously immunised with tetanus toxoid, 33 (79%) reacted to tetanus toxoid and 33 (79%) reacted to Candida albicans. Of eight non-immunised subjects, none reacted to tetanus toxoid although five reacted to Candida albicans. Ten immunodeficient adults previously shown to be anergic to a standard panel of five skin test antigens including Candida albicans, and who had received primary immunisation and booster doses of tetanus toxoid, were anergic on current testing with tetanus toxoid and Candida albicans. Tetanus toxoid in previously immunised subjects has certain advantages as a "recall" DTH test antigen over the standard skin test antigens candidin, mumps, trichophyton, tuberculin and streptokinase-streptodornase used to diagnose cell-mediated immuno-deficiency. It is a sensitive measurement of DTH, it recalls a defined immunological event, it has a low incidence of side effects, and it produces a slight but beneficial boosting of serum antibody to tetanus toxoid.

Adenocarcinoma↗
PubMed1982

Intrahepatic synthesis of immunoglobulin in liver disease.

Patterns of intrahepatic immunoglobulin production were investigated by an in vitro biosynthetic labelling technique which measured the rate of Ig production in liver biopsy fragments. This technique depends on the incorporation of 3H-leucine into proteins synthesized by cells in the biopsy fragment and subsequently released into the culture medium, and precipitation of Ig with monospecific antisera. Intrahepatic Ig production was expressed as counts of radioactivity precipitated/g of liver tissue/24 h. Mean values were high in various inflammatory diseases of the liver, including alcoholic hepatitis (AH) (17 cases), IgG, 87.8, IgA, 105.6 and IgM, 14.7, chronic active hepatitis (CAH) (19 cases), IgG, 86.0, IgA, 56.1 and IgM, 12.6, and acute viral hepatitis (3 cases), IgG, 116.0, IgA, 61.0 and IgM, 32.0, but low in histologically normal livers (6 cases), IgG, 4.5, IgA, 4.8 and IgM, 4.7, alcoholic fatty liver (11 cases), IgG, 9.4, IgA, 11.4 and IgM, 7.1, and miscellaneous non-inflammatory conditions (10 cases), IgG, 8.7, IgA, 11.1 and IgM, 5.0. Photomicrographs were used to measure the density of plasma cells, expressed as cells/mm2 of liver biopsy tissue: mean counts were for AH 5.1, CAH 16.2 and normal liver 0.0. Intrahepatic Ig production in vitro did not correlate with the density of plasma cells in biopsy samples from cases of AH or CAH, nor with serum Ig levels.

Adolescent↗
PubMed1982

Detection of antibodies to tetanus toxoid: comparison of a direct haemagglutination method with a radioimmunoassay.

Two methods of detecting antibodies to tetanus toxoid were compared, a radioimmunoassay (RIA) employing radiolabelled staphylococcal protein A and a direct haemagglutination (HA) method employing sheep erythrocytes coupled to tetanus toxoid with chromic chloride. These were shown to have a similarly high specificity with the HA method showing slightly higher sensitivity. Haemagglutination offers several additional advantages in terms of simplicity, low cost and less requirement for specialised equipment. The assays were also used to demonstrate a transient IgM response after repeated booster injections with absorbed toxin given to seropositive individuals, and these antibodies were found to be protective in biological tests.

Antibodies↗
PubMed1982

Cerebellar cortical degeneration with ovarian carcinoma.

A case is described of progressive cerebellar degeneration in association with ovarian carcinoma, with nearly 4 years elapsing between the onset of neurological illness and the discovery of the carcinoma. Neither treatment with prednisolone nor surgical removal of the tumour effected any improvement, CAT scanning late in the illness showed marked cerebellar atrophy. Histology at post-mortem showed complete loss of cerebellar Purkinje cells. The cerebrospinal fluid gave weak binding to multiple neural components in a solid-phase radio-immuno-assay.

Atrophy↗
PubMed1982

Suppressor cells in stable dialysis and transplant patients.

Assays for suppressor cells were used to investigate the immunological status of uraemic patients (39) and transplant patients (66), and results were compared with those for normal controls (52). The functional assays were depletion of suppressor activity by preincubation (suppressor index) and the concanavalin-A-inducible suppressor assay and, in the uraemic patients, T gamma, T mu, and T0 cells were enumerated. The results of these assays were discordant, supporting previous suggestions that they measure different suppressor cell populations. The level of concanavalin-A-inducible suppressor cell activity was significantly below normal in both uraemic and transplant patients. The number of T mu cells in uraemia was significantly reduced. The findings do not support the possibility that suppressor cells are involved in the immunodeficiency of uraemia or the maintenance of renal transplants. Moreover, it could be suggested that uraemic toxaemia depresses both helper and suppressor modalities with the net effect being a 'pan-deficiency' of immune function.

Cell Division↗
PubMed1982

T lymphocyte subpopulations defined by two sets of monoclonal antibodies in chronic active hepatitis and systemic lupus erythematosus.

Lymphocyte subpopulations were enumerated in human peripheral blood using murine monoclonal antibodies with specificity for all peripheral blood T lymphocytes (OKT3, alpha-Leu 1) and for the helper subset (OKT4, alpha Leu 3a) and suppressor/cytotoxic subset (OKT8, alpha Leu 2a). Patients with chronic active hepatitis (CAH) (23) or systemic lupus erythematosus (SLE) (10), compared with healthy subjects (20), had a lower mean T lymphocyte count. Patients with CAH had normal numbers of suppressor/cytotoxic (TSC) cells, but fewer helper (TH) cells than healthy subjects (0 . 96 +/- 0 . 11 X 10(9)/1 versus 1 . 45 +/- 0 . 15 X 10(9)/1), and those with SLE also had fewer TH cells (0 . 93 +/- 0 . 11 X 10(9)/1). Patients with CAH receiving azathioprine (n = 8) had significantly fewer TSC cells, and a higher TH/TSC ratio (2 . 69 +/- 0 . 35) than those (n = 15) not on this therapy (1 . 85 +/- 0 . 15). When patients taking azathioprine were excluded, no correlation was found between disease activity and the TH/TSC ratio for either disease.

Adult↗
PubMed1982

Segregation of autoantibody to cytoskeletal filaments, actin and intermediate filaments with two types of chronic active hepatitis.

Regional differences in serological features of chronic active hepatitis (CAH) were assessed from study of unselected patients with CAH, 53 from Zagreb, Yugoslavia and 53 from Melbourne, Australia. A group of 29 patients from Zagreb with chronic persistent hepatitis (CPH) was also included. The serological marker studied was immunofluorescence reactivity to cytoskeletal components, actin cables (AC) and intermediate filaments (IF), these being mostly responsible for the smooth muscle antibody reactivity which occurs in CAH. The Zagreb cases of CAH differed from the Melbourne cases by having a significantly lower frequency of anti-AC (8% vs 55%) and a significantly higher frequency of anti-IF (34% vs 15%), and correspondingly had a higher frequency of markers of hepatitis B virus (HBV) infection (HBsAg, 53% vs 8% and anti-HBc, 72% vs 34%), and a differing HLA profile, with HLA BW35 higher (38% vs 14%) and B8 lower (18% vs 56%). This study illustrates the differences among populations in expression of CAH, in that HBsAg is held to specify the HBV-associated type, and antibody to actin is held to specify the autoimmune type. These differences would be determined in part by environmental influences, notably HBV, and genetic influences, notably HLA, and are reflected by the differing patterns of immunofluorescence reactivity with the cellular cytoskeleton.

Actins↗
PubMed1982

Autoantibodies to liver antigens in chronic liver disease. I. A radioimmunoassay for antibody to liver membrane antigens.

A radioimmunoassay using a single cell suspension of glutaraldehyde-treated monkey hepatocytes was developed to measure antibody in human serum to liver membrane antigens. Hepatocytes were exposed to doubling dilutions of test sera in microtitre trays and binding of serum IgG was determined by exposure of the washed cells to 125I-labelled staphylococcal protein A. Specificity of binding was established according to several criteria including use of non-hepatic cells such as monkey kidney cells and various cell lines, IgG depletion of serum, absorption of binding activity by pre-exposure of serum to liver cells, and demonstration that binding was mediated by the F(ab) rather than Fc portions of immunoglobulin molecules. This radioimmunoassay distinguished autoimmune-type chronic active hepatitis (CAH) from other categories of liver disease. It should prove useful for diagnosis and classification of cases of CAH, and could facilitate identification of a liver-specific membrane antigen relevant to pathogenesis of autoimmune hepatitis.

Animals↗
PubMed1981

Issues in immunologically-mediated hepatic injury.

Chronic infection with hepatitis B virus is widespread, and there are other forms of chronic hepatitis in which the host's immune response is pathogenic. A conference study group report assessed faulty immune effector mechanisms. The immune pathways considered were effector cell recruitment and cytolytic mechanisms, including hepatocyte killing by antigen-specific T lymphocytes, non-antigen-specific cells (K and NK cells, macrophages), and antibody plus complement. Also considered were "modulating" effects of surface-located antibody which could result in reduction of killing by T cells of virus-infected hepatocytes which could facilitate chronicity. Evidence for participation of these immune effector processes has not yet been convincing in human chronic hepatitis. Future research must be directed to defining the type and specificity of cytolytic effector systems and circumstances under which host antibody diminishes or augments the activity of such systems, delineating putative auto-antigens, and developing suitable animals models.

Animals↗
PubMed1981

Detection of antibodies to central nervous system antigens by solid phase radioimmunoassay.

A solid phase radioimmunoassay is described which employs 125I-protein-A to detect the presence of antibodies against a panel of cellular and soluble central nervous system (CNS) specific antigens coated onto polyvinylchloride Microtiter plates. Serum antibodies from rabbits immunized against myelin, myelin basic protein (MBP), glial acidic fibrillary protein (GFAP), astroglioma cells, and cerebellar cells were easily detected, and high specificity for each antiserum and antigen was also demonstrable. The assay is applicable to cerebrospinal fluid (CSF) from patients with neurological diseases to detect antibodies against CNS-specific antigens. The assay should be useful for examining cell lines derived from CNS tissue for the presence of brain proteins.

Adolescent↗