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Biomedical subjects

I R Mackay

Publications and source records attributed to I R Mackay.

At least 199 records · Page 11Linked to original sources

Association between anorectal dysplasia, human papillomavirus, and human immunodeficiency virus infection in homosexual men.

Cells from the anorectal mucosa of 61 homosexual men were examined microscopically for evidence of papillomavirus infection and dysplastic changes. There was cytological evidence of dysplasia with concomitant features of human papillomavirus (HPV) infection on at least one occasion in 24 men and of papillomavirus infection without dysplasia on at least one occasion in a further 26: dysplasia was present for over one year in 9 of 14 men who were re-examined. Dysplasia was associated with a history of anal warts, frequent receptive anal intercourse, presence of serum antibody to human immunodeficiency virus (HIV), and immune dysfunction as judged by a low CD4/CD8 ratio, but not with the lifetime number of sexual partners. The association of longlasting dysplasia with anti-HIV was independent of the association with immune dysfunction. Thus infection of anorectal mucosal cells with papillomavirus seems to be frequent among homosexual men and may predispose to dysplasia.

Acquired Immunodeficiency Syndrome↗

Collagen antibodies in rheumatoid arthritis. Significance of antibodies to denatured collagen and their association with HLA-DR4.

The frequency, specificity, and HLA associations of antibodies to collagen were examined in 54 patients with severe rheumatoid arthritis (RA) and in 67 control subjects, using native and denatured bovine type II collagen as reactants in a solid-phase radioimmunoassay. Reactivity to denatured collagen was significantly higher in the RA patients than in the controls (P = 0.004). Reactivity to native collagen was substantially lower than reactivity to denatured collagen and was similar in RA patients and controls. DR4 positive RA patients had significantly greater reactivity to denatured collagen compared with DR4 negative RA patients (P = 0.03), but levels of antibody to native collagen were similar among DR4 positive and DR4 negative patients. These data lend support to the idea that denatured collagen is an important secondary reactant in immune-mediated perpetuation of RA.

Animals↗

Intestinal perforation in Wegener's granulomatosis.

Wegener's granulomatosis is a disease characterised by a necrotising vasculitis and granulomatous inflammation. The localised form involves the upper and/or lower respiratory tracts while in the commoner generalised form there is a widespread necrotising vasculitis and renal involvement. Intestinal involvement, which may be severe, has been detected at necropsy in 24% of cases. Gastrointestinal symptoms are uncommon, however, none being mentioned in a recent series of 87 cases. There has been only one reported case of intestinal perforation secondary to Wegener's granulomatosis. We report a case of small and large bowel perforations in a patient with Wegener's granulomatosis.

Colonic Diseases↗

Myocardial infarction in a young man with systemic lupus erythematosus, deep vein thrombosis, and antibodies to phospholipid.

From the age of 17 a young man had recurrent venous thrombosis, with pulmonary embolism on two occasions. Laboratory investigations showed increased DNA binding, thrombocytopenia, positive antinuclear antibodies, and immunoglobulin A deficiency. A plasminogen activator deficiency was suspected because the euglobulin lysis time was considerably prolonged. Variant lupus was diagnosed. He had a severe myocardial infarct at the age of 20 and subsequent investigations showed the presence in serum of the lupus anticoagulant and antibodies to cardiolipin. The presence of these antiphospholipid antibodies explains the features of his illness and establishes that this case fits into a subset of systemic lupus erythematosus characterised by thrombotic events.

Adolescent↗

'Acute' autoimmune hepatitis.

A previously well young woman presented with an acute hepatitis resembling viral hepatitis and a liver biopsy after 5 weeks showed features of acute hepatitis. Infection with identifiable viruses or other organisms known to cause hepatitis was excluded. Evidence for autoimmune chronic active hepatitis ab initio included prolonged fever, lymphadenopathy, urticaria, arthralgia, Coombs' positive hemolytic anemia, lymphopenia, a markedly raised level of immunoglobulin G and a positive antinuclear antibody test. Liver biopsies after 4 and 28 months showed typical histologic features of autoimmune chronic active hepatitis and the subsequent clinical course was typical, being marked by relapses and remissions responsive to prednisolone. Thus, described here is a woman in whom an acute onset of autoimmune chronic active hepatitis was clinically and histologically identified.

Adult↗

Cell-mediated immunity to hepatitis B virus antigens in mice: correlation of in vivo and in vitro assays.

Cell mediated immunity (CMI) to hepatitis B viral antigens was studied in BALB/mice after immunization with purified hepatitis B surface antigen (HBsAg), or core antigen (HBcAg), with adjuvants. The two in vitro assays for cell-mediated immunity (CMI), utilizing lymph node cells, were release of interferon after exposure to antigen, and blast transformation of lymphocytes, and the in vivo assay was ear swelling at 24 h after local injection of antigen. Immunization with HBsAg or HBcAg with adjuvants induced antigen-specific cutaneous reactivity; if no adjuvants were given, immunization with HBcAg, but not HBsAg, induced cutaneous reactivity. CMI could be adoptively transferred by lymph node cells, but for only a limited period after immunization with HbsAg or HBcAg. The ability of lymph node cells from mice immunized with HBV antigens to transfer adoptively CMI correlated well with their production of interferon after challenge with antigen in vitro, but less well with blastogenesis after challenge with antigen in vitro, or with cutaneous reactivity to antigen in the donor mouse. Reliable antigen-specific lymphokine release assays, rather than blast transformation of lymphocytes or cutaneous reactivity after antigen challenge, are required to assess CMI to HBV antigens in the mouse and, by inference, in man.

Adjuvants, Immunologic↗

Immunological abnormalities in asymptomatic homosexual men: correlation with antibody to HTLV-III and sequential changes over two years.

A prospective study on 100 homosexual male volunteers was designed to examine immunological function in relation to sexual activity and infection with the human T cell lymphotropic virus Type III (HTLV-III). Complete data were available for 71 men. In a comparison with 100 age-matched heterosexual men, the study group of 100 men had a significantly higher mean serum IgG level (12.1 +/- SD 2.7 g/l vs. 10.9 +/- 2.4 g/l, p less than 0.01) and a significantly lower mean number of CD4 (T4) cells (845 +/- 310 X 10(-6)/l vs. 1128 +/- 375; p less than 0.01). For the study group, seropositivity for anti-HTLV-III was present initially in 22 per cent and was associated with a higher mean level of serum IgG and lower mean number of CD4 cells. Among seropositive homosexual men a low CD4/8 ratio was attributable to low numbers of CD4 cells in those without lymphadenopathy and to high numbers of CD8 cells in those with lymphadenopathy. For the seronegative homosexual men, a low CD4/8 ratio as a result of an increased CD8 cell count was present in 12 of 60, and was associated with numerous sexual partners and semen culture positive for cytomegalovirus. In two seropositive subjects a low CD4/8 ratio due to a decrease in the CD4 cell count was predictive of the development of AIDS by some two years. For the 71 men with complete data over two years, indices of cell-mediated immunity, including mean counts of CD4 cells, the CD4/8 ratio, and score for recall of cutaneous delayed type hypersensitivity increased during the first year but not during the second year in both seropositive and seronegative subjects. These increases occurred in association with changes in sexual practices and activity, but could not be attributed to any one particular factor.

AIDS-Related Complex↗

Social correlates of advanced alcoholism and effect of counselling. A paired controlled analysis of 50 patients with a contrast group.

Fifty patients with advanced alcoholism and physical disease were investigated in a paired control study to determine some social indices particular to subjects with their condition. Also assessed was the usefulness of confrontation as a counseling procedure and whether patients with alcoholism in this study accepted referral to, or derived benefit from an outside agency specializing in the rehabilitation of subjects with alcoholism. Social indices which differed significantly between the experimental group and the control group were the number of siblings, marital history, the types of accommodation and a subjective estimate of pleasure derived from life. Indices which did not differ included country of origin, broken home, education, number of children and income. Confrontational counseling and attempts at referral seemed ineffective. It is suggested that the low success rate in the treatment of patients with alcoholism in this study may have been due to the selection of subjects with advanced alcohol-related physical diseases.

Adult↗

Antibody to G-actin in different categories of alcoholic liver disease: quantification by an ELISA and significance for alcoholic cirrhosis.

Autoantibodies to smooth muscle (ASMA), and to actin which is a major determinant of such reactivity, were measured in the serum of 94 patients with three defined categories of alcoholic liver disease, fatty liver, alcoholic hepatitis, and alcoholic cirrhosis, and in controls matched individually by age and sex with the patients. Autoantibody to monomeric G-actin was detected by an ELISA and autoantibody to polymeric F-actin by immunofluorescence staining of fibroblast stress fibers in cultured cells. Values for the ELISA were expressed as a percentage of the value for a strongly reactive standard serum. The mean value for antibody to G-actin in 40 patients with alcoholic cirrhosis (70 +/- 33%) was significantly greater than that for the matched controls (28 +/- 18%), but the mean value for the 30 patients with alcoholic hepatitis (46 +/- 16%) and the 24 with fatty liver (42 +/- 24%) did not differ significantly from the controls. High levels of reactivity with G-actin correlated significantly with HLA B7. ASMA was demonstrable to low titer in 11 of the 94 sera, and positive ASMA reactions by immunofluorescence correlated with high binding values to G-actin in the ELISA. Antibody to F-actin was found in only one serum and no controls. Thus in different liver diseases the reactivity of antibodies to monomeric G-actin and polymeric F-actin may differ, presumably because of specificity for different determinants of the actin molecule. Reactivity to G-actin may distinguish a group of alcoholic subjects in whom a predisposition to autoimmune reactivity is one of the determinants of progression of liver damage to cirrhosis.

Actins↗

Assessment of delayed-type hypersensitivity in man: a comparison of the "Multitest" and conventional intradermal injection of six antigens.

Recall of delayed type hypersensitivity (DTH) as a test for cell-mediated immune competence was assessed in 254 subjects using the Multitest device which delivers seven skin-test antigens intradermally; 77 subjects were tested concurrently by Multitest and a conventional panel of six antigens. Similar results were obtained with Multitest and the conventional panel (R = 0.65). Reproducibility of Multitest between three observers, who independently assessed the aggregate size of reactions (the reaction score) in 45 subjects, was high (R = 0.89). Twenty-four subjects were tested twice 3 months apart; the correlation for the reaction score was high (R = 0.88), demonstrating the suitability of Multitest for serial studies of immune function. Anergy was infrequent (1%) among 110 healthy male controls but was more frequent (8%) among a group of 101 healthy male homosexuals (P less than 0.05). The response rate to particular test antigens differed for the three Australian groups tested and a previously studied French group. Hence there is a need to establish normal profiles of DTH responsiveness for different geographic areas, as well as among subjects of known age and sex, when assessing cell-mediated immunity by the level of DTH responsiveness to multiple skin test antigens.

Adolescent↗

The cellular infiltrate in the liver in auto-immune chronic active hepatitis: analysis with monoclonal antibodies.

The mononuclear cell infiltrate in the liver was analyzed, using a panel of monoclonal antibodies (MAbs) of known specificity, in 10 patients with auto-immune chronic active hepatitis and, for contrast, in 14 with other types of chronic parenchymal liver diseases. In all cases, the mononuclear cell (MNC) infiltrate in the liver consisted mostly of T lymphocytes. Helper (Th) cells were more frequent than suppressor/cytotoxic T cells (Tsc) in the portal tracts and cirrhotic scar tissue, while Tsc were more common in the hepatic parenchyma. The number of Tsc cells in the parenchyma was greatest in patients with histologically active CAH and least in patients with quiescent cirrhosis. "Plasmacytoid" cells with the morphology of plasma cells, a hallmark of the MNC infiltrate in auto-immune CAH, were more frequent in histologically active CAH than in quiescent cirrhosis. These plasmacytoid cells were T200 + ve, and hence of bone marrow origin, but the majority expressed neither membrane nor cytoplasmic immunoglobulin nor any lineage-specific marker antigens, and hence did not fulfil criteria for B lymphocytes; however, these cells were positive for OKT10 and HLA DR. No difference was evident between the MNC infiltrate in the liver in auto-immune CAH and that in the other acute or chronic liver diseases studied, including HBV-associated CAH; hence immunohistological studies do not point to any pathological processes uniquely responsible for the pattern of hepatocyte damage seen in auto-immune CAH.

Antibodies, Monoclonal↗

Another immune-mediated disease associated with hairy cell leukemia: chronic active hepatitis.

This report describes a case of hairy cell leukemia (HCL) occurring with autoimmune chronic active hepatitis (CAH). A 74-year-old woman presented with typical clinical and histologic features of HCL for which splenectomy was performed. 2 years later she developed abnormal liver function tests due to auto-immune CAH. The liver function tests improved promptly after prednisolone therapy. HCL has been reported to occur with several immune-mediated diseases including polyarteritis nodosa, rheumatoid arthritis, hemolytic anemia, cutaneous vasculitis and monoclonal gammopathy with amyloidosis. This report adds a further example of HCL coexisting with an immune-mediated disease, in this case autoimmune CAH.

Aged↗

A graphical presentation of counts of T lymphocyte subpopulations and Th-Ts ratios.

A method is described for the graphical display of the absolute number of two major subpopulations of blood T lymphocytes, the helper (Th) and the suppressor/cytotoxic (Ts) cells, and their ratio, the Th/Ts ratio. Such a display permits distinction between patients with a low Th/Ts ratio due to decreased numbers of Th cells, which correlates with in vivo tests for immunodeficiency and is seen in the acquired immune deficiency syndrome (AIDS), and patients with a low Th/Ts ratio due to increased numbers of Ts cells but no immunodeficiency by in vivo tests, as seen in some homosexual men who have had recurrent infections.

Humans↗