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Biomedical subjects

I R Mackay

Publications and source records attributed to I R Mackay.

At least 217 records · Page 12Linked to original sources
PubMed1985

Primary Sjögren's syndrome after infectious mononucleosis.

A healthy young woman developed primary Sjögren's syndrome after protracted infectious mononucleosis. The diagnosis of primary Sjögren's syndrome was supported by histologic evidence of sialadenitis in labial salivary glands, rheumatoid factor, hypergammaglobulinemia, the HLA-B8 phenotype, and a high titer antibody to the anti-La (SS-B) nucleoprotein that co-precipitated the small ribonucleic acids encoded by Epstein-Barr virus, EBER 1 and EBER 2, as well as "host" RNA. There was strong humoral immunity to the Epstein-Barr nuclear and capsid antigens, but weak T-lymphocyte-mediated cytotoxicity to Epstein-Barr-transformed lymphoblasts, anergy to antigens used to elicit delayed-type hypersensitivity, and a low T-helper/T-suppressor cell ratio. The series of events initiated by infectious mononucleosis was attributed to a genetic defect in the immune response. Association of viral RNA with the La nucleoprotein resulted in a break in immunologic tolerance via a T-cell bypass effect with induction of anti-La (SS-B) by polyclonally activated B lymphocytes leading to autoimmune sialadenitis.

Adult↗
PubMed1985

Reactivity of anti-mitochondrial autoantibodies in primary biliary cirrhosis: definition of two novel mitochondrial polypeptide autoantigens.

Sera that contained autoantibodies to mitochondria (AMA) by immunofluorescence were examined by immunoblotting for reactivity with mitochondrial polypeptides from various mammalian species, yeast, and E. coli. Mitochondrial polypeptides were separated by polyacrylamide gel electrophoresis, were immobilized on nitrocellulose, and were exposed to sera. The sera tested included 18 AMA-positive sera from patients with primary biliary cirrhosis (PBC), two AMA-positive sera from patients without PBC, and 53 AMA-negative sera. All AMA-positive sera reacted with either one or the other, or usually both of two human mitochondrial polypeptides of 70 kilodalton (kD) and 45 kD. The 53 AMA-negative sera were not reactive with the 70 kD polypeptide, but six reacted with the 45 kD polypeptide. The reactivity of the 70 kD and the 45 kD polypeptide was destroyed by brief exposure to trypsin. The counterpart of the 70 kD reactive polypeptide in human mitochondria was a 65 to 70 kD polypeptide in rat and mouse mitochondria, and a 55 kD polypeptide in yeast and in E. coli. The apparent 45 kD polypeptide was similar in all mitochondrial preparations tested, but no counterpart could be identified in E. coli. Beef heart mitochondria were used to show that the reactive polypeptides were present in a semipurified preparation of the F1 portion of mitochondrial H+ ATPase; however, sera did not react with the beta subunit of ATPase, proposed as a candidate mitochondrial autoantigen. The present molecular characterization of two particular antigens should lead to the more precise identification of these antigens, and also to a clearer insight into the pathogenesis of PBC.

Antibody Specificity↗
PubMed1985

Absence of autoimmune serological reactions in chronic non A, non B viral hepatitis.

In 18 cases of chronic liver disease due to non-A, non-B hepatitis virus(es) in which the diagnosis was established by transmission, including chimpanzee inoculation in nine, sera were tested for the autoantibodies characteristically associated with autoimmune chronic active hepatitis. The frequency of autoantibodies to nuclear, smooth muscle, cytofilament, mitochondrial and liver membrane antigens was low, being not greater than that recorded for a normal population, and the few positive reactions obtained were at very low titre. These findings suggest that among cases of 'HBsAg negative' chronic hepatitis, those due to NANB infection are distinguishable from those due to autoimmune chronic hepatitis by negative serological tests for autoantibodies.

Actins↗
PubMed1984

Antibody to human T cell leukaemia virus type III in Australian homosexual men with lymphadenopathy.

Sera from Australian homosexual men with idiopathic lymphadenopathy syndrome (ILS), a disease related to the acquired immune deficiency syndrome (AIDS), were tested for antibodies to two serotypes of human T leukaemia virus (HTLV), types I and III; type III is the type recently recognized in the USA as being associated with AIDS. Sera were tested also from other homosexual men and heterosexual controls. Antibody to high titre to HTLV-III was present in the serum of all six subjects with ILS. In contrast, antibody to low titre was present in only one of six healthy homosexual men and in one of five homosexual men with immunodeficiency but no lymphadenopathy. Antibody to HTLV-III was not detected in serum in the one subject with AIDS who was tested, but was detected in his healthy sexual partner. Antibody to HTLV-I, earlier believed to be related to AIDS, was lacking in all subjects. These results suggest, in an Australian setting, that infection with HTLV-III is the cause of ILS and, by inference, may also be the cause of AIDS. We suggest that there are as yet undetermined factors associated with male homosexual practices which cause immunodeficiency which, in turn, increases susceptibility to HTLV-III, the actual causal agent of ILS and, probably, AIDS.

Acquired Immunodeficiency Syndrome↗
PubMed1984

Effect on immunologic and other indices of adjuvant cytotoxic chemotherapy including melphalan in breast cancer.

Thirty patients with histologically proven node-positive early breast cancer (Stage II) were treated by total mastectomy and axillary clearance and adjuvant chemotherapy regimens including melphalan for 1 year. These patients were studied sequentially, at 3-month intervals, for up to 2 years to assess effects of cytotoxic drugs on immune function, and to determine whether any changes in immune function were related to recurrence. All indices were in the normal range before chemotherapy. The most marked and long-lasting effects of chemotherapy were on numbers of circulating T-cells and B-cells. Mean counts +/- one standard error (X 10(6)/ml) for T-cells before and 12 months after stopping chemotherapy were 1.537 +/- 0.118 and 0.874 +/- 0.120 (P less than 0.01), and for B-cells 0.345 +/- 0.060 and 0.207 +/- 0.030 (P less than 0.01). Functional indices of T-cell and B-cell competence were less compromised than values for cell counts and, in contrast, recovery occurred either during or within 3 months of stopping chemotherapy. This held for both T-cell function measured by delayed-type hypersensitivity (DTH) responsiveness to five recall antigens and mitogenic responsiveness to phytohemagglutinin, and for B-cell function measured by titration of blood group isohemagglutinins. After 4 years the 30 subjects were divided into groups according to whether there was recurrence of cancer (14) or no recurrence (16); the only index predictive of recurrence was depression of DTH to recall antigens. Thus it was found that cytotoxic chemotherapy with melphalan appears to cause long-lasting depression of cell counts but only short-lasting depression of functional indices of immunocompetence, and that levels of immunologic indices during chemotherapy are mostly nonpredictive of recurrence of cancer. The results prompt some caution in the use of adjuvant chemotherapy, at least with melphalan.

Adult↗
PubMed1984

Transfer of human nasal papilloma into nude mice.

We transferred tumor tissue from two inverted schneiderian nasal papillomas to hypothymic nude mice. Tissue from one tumor, which later underwent malignant change, was transferred three times. Forty days lapsed before growth was evident, with a subsequent period of rapid growth. Histologic appearances of the primary tumor and xenografts were similar. Although the data are derived from only two cases, our findings suggest that the capacity of these tumors to grow in nude mice may be an index of their malignant potential.

Adolescent↗
PubMed1984

A strong association between the antinuclear antibody anti-La (SS-B) and the kappa chain allotype Km(1).

The distribution of immunoglobulin allotypes of the Gm and Km systems was examined in 51 patients with antinuclear antibodies (ANA), which reacted with two saline-extractable non-DNA nuclear antigens, anti-La (SS-B) and anti-RNP, which characterize certain multisystem autoimmune diseases. Forty-six percent of the 26 patients with anti-La were positive for the Km(1) allotype compared with 14% of the 35 with anti-RNP and 16% of 1204 of healthy subjects (corrected P value less than 0.005). The high frequencies of the Km(1) allotype (46%), female sex (100%), and the HLA-B8, DR3 phenotype (greater than 90%) in patients with anti-La are indicative of a substantial inherited predisposition to the development or expression of this autoantibody. The strong association between the Km(1) allotype and the anti-La response may be due to linkage disequilibrium between genes coding for the constant region of immunoglobulin kappa light chains and genes coding for the variable regions of kappa light chains which confer antibody specificity for the special configuration of the ribonucleoprotein known as La.

Antibodies, Antinuclear↗
PubMed1984

Elicitation of experimental allergic encephalomyelitis (EAE) in mice with the aid of pertussigen.

Pertussigen, one of the biologically active proteins from Bordetella pertussis, was found highly active as an adjuvant to promote the induction of experimental allergic encephalomyelitis (EAE) in (SJL X BALB/c)F1 mice that had received at the same time an injection of mouse spinal cord (MSC) homogenized in complete Freund's adjuvant containing 4 mg of Mycobacterium tuberculosis H37RA per milliliter (CFA-H37). In this system 2 mg of MSC induced EAE, but a dose of 4 mg was more effective. As little as 250 ng of pertussigen facilitated induction of EAE, and 400 ng uniformly did so. Pertussigen was most effective when given iv from 1 day before to 5 days after administration of MSC homogenized in CFA-H37, when a uniform and severe disease was induced 11-13 days after immunization. Pertussigen given as late as 20 days after MSC-CFA-H37 still precipitated a mild form of EAE which appeared 8-12 days after the injection of pertussigen. When pertussigen was given 5 days after immunization, a chronic, nonfatal type of EAE was induced, and this persisted for the entire 74 days of observation. Histologic findings in the brain and spinal cord 15 days after sensitization in mice which received pertussigen and developed EAE showed perivascular infiltrates consisting mainly of mononuclear cells.

Animals↗
PubMed1984

Adoptive transfer of experimental allergic encephalomyelitis in mice with the aid of pertussigen from Bordetella pertussis.

Adoptive transfer of experimental allergic encephalomyelitis (EAE) in (SJL X BALB/c)F1 mice was accomplished by an iv injection of 2.4 to 4.7 X 10(7) lymph node cells (LNC) from mice immunized with mouse spinal cord emulsified in complete Freund's adjuvant when both donors and recipients had been treated iv with 400 ng of pertussigen at the time of immunization for the donors and on transfer of cells for the recipients. Pertussigen was essential in both donors and recipients for development of frank EAE. Signs of EAE in recipients were delayed, appearing 21-23 days after cell transfer; the maximum response at about Day 27 is considerably delayed in comparison with other reported studies on passive transfer of EAE. Histologically, recipient mice with paralysis due to EAE had typical perivascular infiltrates of mononuclear cells in the brain and spinal cord. The mechanisms by which pertussigen promotes the development of EAE after adoptive transfer of sensitized LNC are uncertain.

Animals↗
PubMed1984

Production of experimental allergic encephalomyelitis with the aid of pertussigen in mouse strains considered genetically resistant.

Strains of mice (BALB/c An Bradley/Wehi, C57B1/10J, CBA/ca H Wehi, DBA/2 Wf, A/J Wehi), thought to be genetically resistant to experimental allergic encephalomyelitis (EAE) and known to be resistant to becoming hypersensitive to histamine after administration of pertussis vaccine were tested for their ability to develop EAE when purified pertussigen was included in the immunization. It was found that C57B1/10J, CBA/ca H Wehi, BALB/c An Bradley/Wehi and DBA/2 Wf developed typical signs and histologic evidence of EAE. The A/J Wehi and the B10D2/n Sn (not previously tested) strains developed only mild signs of EAE, while the known susceptible (SJL/J X BALB/c An Bradley/Wehi) F1 hybrids developed severe EAE. Histologic evidence of EAE was lacking in A/J Wehi mice and was minimal in B10D2/n Sn mice. These results suggest that neither the H-2 complex nor the gene controlling susceptibility to sensitization to histamine by administration of pertussigen are wholly responsible for susceptibility to EAE.

Animals↗
PubMed1984

Autoantibodies reactive with small ribonucleoprotein antigens: a convergence of molecular biology and clinical immunology.

Autoantibodies to nuclear antigens (ANA) occur in patients with systemic lupus erythematosus (SLE) and other multisystem autoimmune diseases. Although heterogeneous, there are 2 major groups, autoantibodies to DNA and autoantibodies to non-DNA antigens, the latter including ANAs to the soluble or "extractable nuclear antigens" (ENA). This review discusses those ENAs which are ribonucleoproteins (RNPs) consisting of small RNA molecules (80-400 nucleotides) attached to non-histone proteins: these are called small nuclear (sn) or small cytoplasmic (sc) ribonucleoproteins according to their location in the cell and at least some are known to play an important role in nuclear metabolism. ENAs can be immunoprecipitated from crude preparations of nuclei by sera from patients with multisystem autoimmune diseases and, after removal of the associated proteins, the RNA components can be analyzed by gel electrophoresis. This shows 3 main categories of small RNAs: the U group comprising U1-U6 snRNAs, the Ro group comprising small nucleocytoplasmic RNAs, and the La group comprising several species of cellular snRNAs as well as the Ro scRNAs. La, in addition, includes small RNAs encoded by adenovirus (VA I, VA II), Epstein-Barr virus (EBER 1, EBER 2) and vesicular stomatitis virus (leader RNA). In the case of each group, the RNAs themselves are not antigenic but become so when associated with proteins, most of which are uncharacterized. The U snRNAs, located in the nucleus, are transcribed by RNA polymerase II and appear to be involved in the splicing of introns from mRNA. Sera from patients with mixed connective tissue disease (MCTD) react with RNPs containing U1 RNA and sera from patients with SLE react with U RNPs containing U1, U2, U4, U5 and U6 RNAs, collectively known as the Sm antigen. The Ro RNAs are transcribed by RNA polymerase III and have no known function. Sera from patients with primary Sjögren's syndrome and some cases of SLE react with Ro scRNPs. The La RNAs are also transcribed by RNA polymerase III and are located mostly in the nucleus; functionally the protein associated with the La RNAs appears to be important in RNA polymerase III transcription. Sera from patients with primary Sjögren's syndrome react with the heterogeneous group of both cellular and viral RNAs which constitute the La RNP antigen. Sera of patients with SLE, scleroderma, polymyositis and dermatomyositis also react with RNPs relevant to nuclear metabolism and further definition of these RNPs is awaited. Many advances can be expected from the convergence of molecular biology and clinical immunology exemplified by the current studies on ENAs.(ABSTRACT TRUNCATED AT 400 WORDS)

Antibodies, Antinuclear↗
PubMed1984

Activated lymphocyte killer cells derived from melanoma tissue or peripheral blood.

Lymphoid cells infiltrating metastatic melanomas were grown directly from cell suspensions of tumour tissue by the addition of T cell growth factor. Lymphoid cells grew out at the expense of tumour cells in six of seven freshly excised tumours, and cells from two cultures were expanded for in vitro testing of cytolytic function against different target cells. Early in culture the tumour derived lymphocytes killed fresh autologous melanoma cells and, particularly later in culture, were highly and non-specifically cytolytic for cultured melanoma and non-melanoma cells. Cultured peripheral blood lymphocytes from patients with melanoma, and from normal subjects, were cytolytic to the same degree as tumour derived lymphocytes, and also resembled cells grown from tumour tissue in possessing acid phosphatase activity which was resistant to tartrate. Cultured lymphoblasts from both tumour and peripheral blood had a T cell phenotype when analysed with monoclonal antibodies. An in vitro co-culture system was employed to study the kinetics and the precursors of these non-specific killer cells among blood mononuclear cells. Blood mononuclear cells cultured with irradiated B lymphoblasts led to the generation of non-specific cytolytic cells, referred to as activated lymphocyte killer (ALK) cells, after 7-10 days of culture and the progenitors of these ALK cells were demonstrated to be distinct from those of specific cytolytic T cells.

Cells, Cultured↗
PubMed1984

Effects of the oestrogen antagonist tamoxifen on disease indices in systemic lupus erythematosus.

Sex hormones are possible determinants of systemic lupus erythematosus (SLE). Hence treatment with tamoxifen, which competes for oestrogen receptors, was assessed in 11 female patients with stable SLE in a double-blind crossover trial. The indices used included clinical signs of SLE, renal function, leucocyte counts, serum antinuclear and anti-DNA activity, and serum levels of complement and immune complexes. No patient improved on tamoxifen and two deteriorated. Significant side effects were encountered. The trial yielded no evidence that tamoxifen had an ameliorative effect on clinical or laboratory indices of activity of SLE.

Adult↗
PubMed1984

Antibodies to liver cell membrane antigens in chronic active hepatitis (CAH). III. Partial characterization of the liver cell membrane antigens and comparison of reactivities in sera from patients with various liver diseases.

The reactivity of sera in liver diseases was investigated by an immunoradiometric assay for antibody to liver membrane antigens (LMAg). Serum reactivity was similar using glutaraldehyde treated hepatocytes from man and several animals, but the reactivity with human hepatocellular carcinoma cell lines was weak and irregular. F(ab)2 fragments from reactive sera were used in competitive inhibition experiments to ascertain whether anti-LMAg from different liver diseases reacted with the same or different antigenic determinants of the liver membrane. Sera from different patients with autoimmune CAH reacted predominantly with the same membrane components, as did sera from hepatitis B virus associated CAH (CAH-B); however sera from acute viral hepatitis A did not and, since such sera were reactive to LMAg in the assay, other membrane antigens are presumably involved. Enzymatic treatment of viable hepatocytes was performed to determine the nature of the reactive antigen(s): proteases or periodate resulted in reduced binding of reactive sera, but neuraminidase did not, suggesting that the LMAg recognized by CAH sera comprises species non-specific membrane glycoproteins. We conclude, on the basis of quantitative data from a immunoradiometric assay, that antibody to LMAg is more probably reactive than pathogenic, and that assessment of the antigenicity of specific membrane components is necessary.

Actins↗