PubMed Health⌕ Search

Biomedical subjects

I R Mackay

Publications and source records attributed to I R Mackay.

At least 235 records · Page 13Linked to original sources
PubMed1984

Survival and tissue localization of xenogeneic human lymphocytes in hypothymic nude mice: observations in normal subjects and multiple sclerosis.

The feasibility of using the hypothymic nude mouse as a transfer system for the study of cellular autoimmunity, by injection and tracing of 51chromium (Cr) or fluorescein labelled lymphocytes from humans, allogeneic or syngeneic mice was investigated. The localization of the injected cells was studied by radioisotopic counting or microscopy. For mouse cells there was better survival of syngeneic than allogeneic cells, and the pattern of distribution of injected mouse lymphocytes differed markedly from that of xenogeneic human lymphocytes. Thus, the lymph nodes and spleen were the predominant sites of localization of transferred syngeneic (BALB/c) lymphocytes, indicative of long recirculation of these cells, whereas the liver was the predominant site of localization of transferred human lymphocytes, and there was no evidence for recirculation of these cells. In studies on patients with multiple sclerosis, lymphocytes did not localize in neural tissue. The data indicate that the nude mouse is unlikely to be useful for the study of the tissue distribution of dispersed xenogeneic (human) lymphocytes.

Adult↗
PubMed1984

Genetics of carbon tetrachloride-induced liver injury in mice. II. Multigenic regulation.

Mice from many different congenic inbred strains were given an intramuscular injection of carbon tetrachloride (CCl4) in olive oil to determine the genetic influences on induction of, and recovery from, liver damage. Liver and blood samples were taken at days 1, 4 and 7. The degree of necrosis and lymphoid infiltration appeared to be controlled, qualitatively and quantitatively, by both H-2-linked and Ah-linked genes. Strain differences were noted in the patterns of hepatocellular necrosis and the proportions of lymphoid, monocytic and other inflammatory cells which characterized the infiltrating population. Kinetic studies of F1 hybrids from matings between the susceptible BALB/cJ male parent and the resistant SJL/J female parent suggested that two dominant genetic influences play a major role in CCl4-induced liver damage. The gene contributed from the BALB/cJ parent affects the extent of liver necrosis and a second gene from SJL/J augments recovery. These results suggest, therefore, that the CCl4-induced liver damage and subsequent recovery are under multigenic control by H-2, Ah and possibly other genes.

Animals↗
PubMed1984

Antinucleolar autoantibodies demonstrated by monolayers of human fibroblasts in sera from patients with systemic lupus erythematosus, progressive systemic sclerosis and chronic active hepatitis.

Antinucleolar antibody (ANoAb) was tested for in sera from 25 patients with systemic lupus erythematosus (SLE), 61 with progressive systemic sclerosis (PSS), 22 with chronic active hepatitis (CAH) and 28 healthy persons, using immunofluorescence reactivity with acetone-fixed monolayers of cultured human fibroblasts, and a procedure to reveal ANoAb when other antinuclear antibodies were concurrently present. ANoAb was found on direct testing in sera from 6 patients with SLE, 15 with PSS and 7 with CAH, but not in any of 28 sera from healthy persons; homogeneously reactive antinuclear antibody was also present in the serum of these 6 cases of SLE, in 6 of the 15 with PSS and in 3 of the 7 with CAH and, in SLE specifically, pre-treatment of fibroblast monolayers with DNase "unmasked" the presence of ANoAb in a further 7 sera which had shown only homogeneous nuclear staining in fibroblasts. ANoAb belonged to the IgG, IgM and IgA class in sera from cases of SLE and PSS, and to only the IgG and IgM class in sera from cases of CAH. ANoAb titres were highest in patients with PSS. ANoAb were sensitive to RNase in 5 cases, to RNase and DNase in 6, and were sensitive to combinations of RNase, DNase, NaC1, and trypsin in the remaining cases. We conclude that (i) fibroblast monolayers are a suitable substrate for the demonstration of ANoAb, (ii) homogeneous staining of cell nuclei may mask ANoAb, so that the incidence of ANoAb becomes higher in SLE than in PSS, (iii) low-titre ANoAb in CAH not visualized in frozen tissue sections may be detected on fibroblast monolayers, and (iv) nucleolar antigens probably include RNA, RNA bound to DNA, and RNA bound to proteins.

Autoantibodies↗
PubMed1983

A rapid micromethod for evaluating T cell subsets in blood using monoclonal antisera.

A simple accurate method is described for enumerating T cell subsets in whole blood. The method, which depends on indirect immunofluorescence using biotin-coupled monoclonal antisera and fluorescein-coupled avidin, and propidium iodide for nuclear counterstaining, was compared with the conventional method based on initial separation of lymphocytes by density flotation and exposure to monoclonal antisera. Accurate identification of mononuclear cells in whole blood by nuclear staining with propidium iodide was established. The whole blood method gave numbers for T cell subpopulations generally comparable with those obtained by the conventional method, but slightly higher numbers of Leu2a+ cells were found by the whole blood method, and shown to be higher because of selective loss of Leu2a+ plastic-adherent cells in the conventional method. The whole blood method is quicker, uses only 0.5 ml blood and is economical in use of monoclonal reagents.

Antibodies, Monoclonal↗
PubMed1983

Effect on natural killer and antibody-dependent cellular cytotoxicity of adjuvant cytotoxic chemotherapy including melphalan in breast cancer.

Natural killer (NK) cell activity and antibody-dependent (K) cell activity were studied sequentially in 30 patients with early node-positive breast cancer entered into an adjuvant chemotherapy trial. The drugs used were melphalan, and melphalan with methotrexate, given for 12 months. Estimations were made 3-monthly during chemotherapy, and then at 15 and 24 months to assess recovery. Mean values for NK-cell activity during chemotherapy were significantly lower than the mean pre-chemotherapy baseline value at all time-points from 3 to 15 months, but there was recovery by 24 months. Mean values for K-cell activity during chemotherapy did not appear to differ from the mean pre-chemotherapy value, but variability in individual values was high. Over a 4-year follow-up period, a comparison of 16 patients who did not develop recurrent breast cancer with 14 who did showed that NK-cell activity was significantly lower in the latter group 12 months after the start of chemotherapy.

Antibody-Dependent Cell Cytotoxicity↗
PubMed1983

Transfer of murine experimental autoimmune encephalomyelitis and cell-mediated immunity to myelin protein is effected by Lyt-1 cells.

Cellular transfer of experimental autoimmune encephalomyelitis (EAE) was effected in mice with lymph node cells (LNC) from appropriately immunized donors. Pretreatment of LNC with anti-Lyt-1 and Lyt-2,3 antibodies indicated that the transfer of both EAE and a cell-mediated immune response in vitro to MBP was dependent on a subpopulation of T lymphocytes expressing the phenotype associated with the helper and cell-mediated delayed hypersensitivity functions, Lyt-1+, 2-.

Animals↗
PubMed1983

Human natural killer cells, activated lymphocyte killer cells, and monocytes possess similar cytotoxic mechanisms.

The relationship between the killing mechanisms of human natural killer (NK) cells, mitogen- and mixed-lymphocyte-culture-induced activated lymphocyte killer (ALK) cells, and monocytes was investigated with a monoclonal antibody. The IgG2 antibody 9.1C3 was prepared from mice immunized with purified human large granular lymphocytes and selected from clones that inhibited NK cell killing. The 9.1C3 antibody bound to all mononuclear cells but not to granulocytes or K562 cells, and it selectively blocked killing of K562 targets by both NK and ALK cells without affecting the binding of effector to target cells. The antibody blocked killing when present from time zero and it still inhibited partially even when added 1 hr after initiation of the lytic reaction. Killing of Epstein-Barr virus-transformed B lymphoblasts by classical cytotoxic T lymphocytes was not inhibited. Of interest, 9.1C3 did block the killing of K562 target cells by cultured peripheral blood monocytes. Other monoclonal antibodies that bound to monocytes did not block killing, and a nonspecific effect of the antibody on monocytes was excluded. These data suggest that NK cells, ALK cells, and monocytes can kill tumor cell targets by using similar lytic mechanisms.

Animals↗
PubMed1983

HLA and Gm genes in systemic lupus erythematosus.

HLA and Gm phenotypes were compared in 53 patients with unequivocal systemic lupus erythematosus (SLE) and in 180 healthy subjects. SLE was associated with HLA-B8 (relative risk (RR) = 3.5, P less than 0.001) and with HLA-DR3 (RR = 2.8, P less than 0.01). There was an increased risk of SLE with HLA-B8/B27 (RR = 27.6) and with HLA-B15/B35 (RR greater than 13) and, in contrast, the risk was decreased in subjects with HLA-B40 (RR = 0.3). The risk of SLE in subjects who were heterozygous for the Gm phenotypes a,f,x; b,g was increased (RR = 2.0, P = 0.03) relative to the risk in subjects who were homozygous for these Gm phenotypes. These findings suggest that susceptibility to SLE is influenced by one or more genes in linkage disequilibrium with the HLA-B8-DR3 haplotype, by "augmentor" or "protector" genes associated with other HLA antigens and by separate genes, possibly VH genes, in linkage disequilibrium with the Gm (CH allotype) locus.

Genes, MHC Class II↗
PubMed1983

Autoantibodies to small nuclear ribonucleoproteins. A strong association between anti-SS-B(La), HLA-B8, and Sjögren's syndrome.

The heterogeneity within multisystem autoimmune disease was evaluated according to the presence of antinuclear antibodies to ribonucleoproteins and the HLA-A1, B8, DR3 phenotype. Patients with various multisystem autoimmune diseases were tested by a highly sensitive radioimmunoassay for autoantibodies to the small nuclear ribonucleoproteins known as SS-B (La) and ribonucleoprotein (RNP), and HLA phenotypes were determined. The 210 patients included 64 with systemic lupus erythematosus (SLE), 11 with "atypical SLE", 41 with Sjögren's syndrome, 22 with mixed connective tissue disease (MCTD), 21 with rheumatoid arthritis (RA), 16 with primary biliary cirrhosis (PBC) and 35 with autoimmune chronic active hepatitis (A-CAH). Anti-SS-B (La) was present in high frequency in Sjögren's syndrome and was strongly associated with HLA-A1, B8, DR3. Anti-RNP was detected predominantly in MCTD and had no association with HLA-A1, B8, DR3. There were sharply defined serological and genetic differences between primary Sjögren's syndrome and Sjögren's syndrome associated with RA. Anti-SS-B (La) was present in 70% of patients with primary Sjögren's syndrome but in none with Sjögren's syndrome with RA, and the respective frequencies of HLA-A1, B8, and DR3 were 88%, 94% and 75% in the former compared with 38%, 29% and 14% in the latter. Thus primary Sjögren's syndrome differs immunogenetically from Sjögren's syndrome with RA. There was a notable absence of anti-SS-B (La) in PBC, an autoimmune disease associated with the Sjögren's syndrome. These findings illustrate the value of studying immunological and genetic markers in detecting heterogeneity within groups of diseases whose symptoms cannot be distinguished clinically.

Antibodies, Antinuclear↗
PubMed1983

Hepatocellular carcinoma in a patient with sarcoidosis-associated chronic active hepatitis and the MZ alpha-1-antitrypsin phenotype.

A case of primary hepatocellular carcinoma is described in a patient with long-standing sarcoidosis of the liver associated with chronic active hepatitis, and the MZ alpha-1-antitrypsin phenotype. This association appears to be unique. The respective roles of alpha-1-antitrypsin deficiency, sarcoidosis and chronic active hepatitis in the development of hepatocellular carcinoma in this case are uncertain.

Adult↗
PubMed1983

Chronic active hepatitis in alcoholic patients.

The histologic appearances characteristic of chronic active hepatitis (CAH) were observed in liver biopsies of seven patients among whom alcohol abuse was the only identifiable determinant of liver disease. Clinical, hematologic, biochemical and histologic features in these patients were contrasted with those of 20 patients with typical alcoholic hepatitis. For the CAH group, the liver was less enlarged below the costal margin, a palpable spleen was more frequent, the mean neutrophil count was lower, and there was a lower mean level of transaminase enzymes. In both groups there was minimal evidence of the serologic markers of autoimmune CAH or antecedent hepatitis B virus (HBV) infection. Histologically, all liver biopsies in the CAH group showed perilobular "piecemeal" necrosis, "rosette" formation and dense portal and septal lymphoid infiltrates, in contrast to the fatty change, Mallory bodies and intralobular neutrophil clusters of the alcoholic hepatitis group. In the CAH group, a second liver biopsy was assessed after a period during which alcohol consumption was known; histologic improvement or deterioration correlated with abstinence or continuation of drinking. Thus "alcoholic" CAH has some clinical and histologic features distinct from those of typical alcoholic hepatitis, but the two types were similar in other respects including dependence of the course of disease on continuing use of alcohol.

Adult↗
PubMed1983

Chronic hepatitis after successive halothane anesthetics.

A woman with cancer of the cervix had over a 4-week period three anesthetics with halogenated anesthetic agents, halothane, enflurane and halothane. 1 day after the third halothane anesthetic she developed fever and jaundice with biochemical evidence of severe hepatitis. Liver biopsy 10 days after the onset of jaundice showed features of acute hepatitis with bridging necrosis and piecemeal necrosis. A second biopsy after 10 months showed quiescent cirrhosis with residual piecemeal necrosis. The case is reported as a further example of halothane hepatitis evolving to cirrhosis of the liver.

Anesthesia, Inhalation↗
PubMed1983

In vitro growth of B lymphocytes infiltrating human melanoma tissue by transformation with EBV: evidence for secretion of anti-melanoma antibodies by some transformed cells.

Epstein Barr virus was used to transform the B lymphocytes infiltrating metastatic tumor tissue from seven patients with melanoma. In this way it was possible to establish continuously growing B lymphoblastoid cell lines (LCL) derived from the tumor-infiltrating B lymphocytes from each of the seven patients. Antibody production of up to 50 micrograms/ml could be achieved by such cultures, and the lymphoblastoid cells could be cloned readily by limit dilution on a feeder layer of irradiated fetal fibroblasts. Preliminary analysis of the antibodies produced by lymphoblastoid cell lines established from tumors from two of the patients indicated that most were of IgM type and bound to a panel of melanoma cell target cells, as well as to some nonmelanoma tumor cell lines. Cloned LCL were produced from the tumor-infiltrating B cells from one of the patients, and of 100 such clones tested, 9% secreted antibody that bound to autologous tumor cells, and one of these clones produced antibody that appeared to be melanoma specific.

Animals↗
PubMed1983

ELISA assay for IgG autoantibody to G-actin: comparison of chronic active hepatitis and acute viral hepatitis.

An ELISA was developed to test for IgG autoantibody to rabbit skeletal muscle G-actin in liver disease. To express results of the ELISA, we used a single reference serum with known high anti-actin activity, and assessed binding of test sera as a percentage of that displayed by the reference antiserum. Antibody to G-actin was measured in 40 sera from patients with chronic active hepatitis (CAH), 39 from acute viral hepatitis A (Hep A), 46 from acute viral hepatitis B (Hep B), 23 from non-A, non-B hepatitis (Hep non-A, non-B), 31 from systemic lupus erythematosus (SLE), 21 from scleroderma and 93 from normal persons. The results were compared with those obtained using indirect immunofluorescence tests with frozen sections of rodent stomach or fibroblast monolayers as substrates. Anti-G-actin activity of serum was significantly higher (P less than 0.001) in CAH (mean 63% +/- 23, range 18-110) than in controls (mean 15% +/- 12, range 0-51), systemic lupus erythematosus (mean 25% +/- 16, range 8-76), scleroderma (mean 23% +/- 13, range 3-59), Hep A (mean 24% +/- 11, range 6-25), Hep B (17% +/- 8, range 2-36), or Hep non-A, non-B (mean 23% +/- 11, range 7-53). There was no significant difference (P greater than 0.05) in the occurrence of anti-G-actin activity of serum in Hep A, Hep B or non-A, non-B compared with controls. At an ELISA reading of greater than or equal to 40% (mean + 2 s.d. of controls) the assay detected autoantibodies to G-actin in 85% of CAH, compared to 80% on fibroblast monolayers and 70% on rodent stomach. The ELISA described in the present study is a simple, sensitive and quantitative assay for autoantibody to G-actin. It should prove useful in assessing subspecificities of actin antibodies in liver diseases, and in differential diagnosis, particularly CAH from acute viral hepatitis.

Actins↗
PubMed1983

The oligodendroglial cell: biology and immunology and relationship to multiple sclerosis.

Myelin is elaborated and maintained in the central nervous system by the oligodendrocyte. The interaction between the oligodendrocyte and the neuron which initiates myelin formation is of major importance, and modern immunological technology using monoclonal antibodies and the fluorescence activated cell sorter have provided the means by which purified homogeneous populations of oligodendrocytes and neurons can be studied in vitro. The oligodendrocyte appears to have limited capacity to divide in situ which may contribute to the vulnerability of such cells in disease states; however it has been found that under certain culture conditions oligodendrocytes can proliferate in vitro. Multiple sclerosis (MS) is associated with loss of oligodendrocytes within the lesions and the intractability of the disease compared to other demyelinating conditions, both experimental and clinical, suggests, that the oligodendrocyte is the primary target of this disease. The cause of oligodendrocyte destruction is as yet uncertain although an immunological response may be in part responsible. The possible mechanism of immune recognition and cytolysis are discussed with regard to the unique nature of the nervous system.

Autoantibodies↗
PubMed1983

Antibodies to liver membrane antigens in chronic active hepatitis (CAH). II. Specificity for autoimmune CAH.

An immunoradiometric assay for IgG class autoantibody to liver membrane antigens, based on serum binding to glutaraldehyde treated monkey hepatocytes, was used to examine sera from patients with chronic active hepatitis (CAH) and other acute and chronic liver diseases. All sera from normals and patients showed binding, up to a titre of 1/2,048. For comparison of assays, results were normalized by selecting two reference sera, one with a high degree of binding, and one from a healthy subject with a low degree of binding: at a dilution of 1/2,048, these sera were given binding values of 100% and 0%. The values for the binding of unknown sera at the same dilution were calculated from these two reference values. For 26 patients with autoimmune CAH, the mean (+/- s.d.) percentage binding value (70 +/- 33%) was significantly higher than the mean value for 26 healthy subjects (10 +/- 15%), and high binding values were significantly associated with biochemically active hepatitis. The mean percentage binding value was moderately increased for eight patients with HBsAg associated CAH (42 +/- 12%), 13 patients with alcoholic hepatitis with cirrhosis (37 +/- 25%) and 45 patients with acute viral hepatitis A (40 +/- 27%) or B (52 +/- 37%). At a cut-off binding value of 65%, the assay as a single diagnostic procedure was shown to have a 70% sensitivity and a 95% specificity for the diagnosis of autoimmune CAH. Better understanding of the pathogenetic significance of antibodies to liver membrane antigens in CAH and other liver diseases will depend upon biochemical analysis of the presumably multiple antigenic determinants on the hepatocyte membrane.

Antigens, Surface↗