PubMed Health⌕ Search

Biomedical subjects

I R Mackay

Publications and source records attributed to I R Mackay.

At least 181 records · Page 10Linked to original sources
PubMed1987

Molecular cloning of the liver-specific rat F antigen.

F antigen is a 43-kDa widely conserved liver protein that has been intensively used in studies of immunogenicity and tolerance; two murine allotypes have been identified. Immunization of specific responder inbred strains with liver homogenates from the opposite allotype leads to precipitating antibody and cell-mediated immunity against F. The antibodies produced are autoantibodies as they react equally well with self. We have identified a cDNA clone from rat liver that reacts with alloantisera to F. The fused polypeptide produced by the clone was shown to correspond to F by several experiments. First, alloantisera to F antigen reacted with the cloned fused polypeptide, but not control recombinant clones. Second, mice immunized with the fused polypeptide generate an antibody response that reacts specifically with the 43-kDa protein of mouse liver homogenates and with highly purified F antigen. Finally, both anti-F allosera and sera from mice immunized with the fused polypeptide react with the same 43-kDa liver protein on two-dimensional immunoblots. The nucleotide and deduced amino acid sequence of the clone are presented and the sequence was found to have a significant homology with L28, an Escherichia coli ribosomal protein. The availability of recombinant F antigen will allow definitive questions to be addressed with respect to epitopes and specifically the identification of the T cell epitope which allows for autoimmune responses.

Amino Acid Sequence↗
PubMed1987

Identification and specificity of a cDNA encoding the 70 kd mitochondrial antigen recognized in primary biliary cirrhosis.

Mitochondrial autoantibodies are characteristic of the disease primary biliary cirrhosis (PBC), but the immunoreactive mitochondrial antigens have not been defined. We used a rat liver cDNA library in lambda gt 11-Amp3 to clone a 1370-base pair insert that coded for a polypeptide reactive with PBC sera. This insert was subcloned for expression into pBTA224, a plasmid vector in the same reading frame as lambda-Amp3. A positive clone, designated pRMIT, that expressed a fused polypeptide of 160 kd, was recognized by 25 of 25 sera from patients with PBC and none of 96 sera from normal persons or patients with systemic lupus erythematosus, rheumatoid arthritis, or chronic active hepatitis. This fused polypeptide was shown to correspond with the 70 kd mitochondrial autoantigen by several experiments. First, lysates of pRMIT in J101 absorbed out the 70 kd reactivity of PBC sera when probed against fractionated placental mitochondria. Second, affinity-purified antisera reactive with the fused polypeptide also reacted with the 70 kd mitochondrial antigen. Third, such affinity-purified antisera produced the characteristic anti-mitochondrial pattern of immunofluorescence on tissue sections. Finally, immunization of BALB/c mice with the fused polypeptide elicited antibodies to mitochondria. These murine antibodies reacted with the 70 kd mitochondrial protein and also produced typical mitochondrial immunofluorescence on tissue sections. The nucleotide and amino acid sequence of the recombinant protein, which encodes for approximately a 48 kd protein, showed no significant homologies with known proteins, and there were no homologies with mitochondrial genomic DNA. The availability of a recombinant form of the 70 kd mitochondrial autoantigen will allow several definitive questions to be addressed in PBC, including identification of B cell epitopes, T cell recognition, and a model of PBC in mice.

Amino Acid Sequence↗
PubMed1987

Treatment of chronic active hepatitis and other liver diseases with corticosteroid agents.

The term chronic active hepatitis covers aetiologically different conditions with similar histological features. Autoimmune chronic active hepatitis - the type that was described originally - is the only type which responds well to prednisolone therapy. Autoimmune chronic active hepatitis can be differentiated from other types by serological and other markers. Treatment with prednisolone should be given for at least two years, with adjustment of dosage according to the serum levels of aspartate transaminase; maintenance does should be 8-12 mg a day. Azathioprine (50-100 mg a day) may be given concurrently as a corticosteroid-sparing agent. Prednisolone therapy in patients with autoimmune chronic active hepatitis enhances the quality of life and survival is prolonged greatly; currently the survival rate after 10 years for prednisolone-treated cases is at least 70%. Prednisolone is not effective in hepatitis B-associated chronic active hepatitis and may be deleterious. In cryptogenic chronic active hepatitis, in which markers of autoimmunity or hepatitis B viral infection are lacking, a trial of prednisolone therapy may be given for three months, and continued only if the indices of disease activity indicate a response. Corticosteroid agents have not proved of benefit in other liver diseases, including alcoholic hepatitis and acute liver failure, and a beneficial effect in primary biliary cirrhosis is yet to be established.

Adrenal Cortex Hormones↗
PubMed1987

Intramuscular versus low-dose intradermal hepatitis B vaccine. Assessment by humoral and cellular immune response to hepatitis B surface antigen.

The capacity of hepatitis B surface antigen (HBsAg) vaccine (which was administered by the conventional intramuscular route or as a one-tenth dose by the intradermal route) to elicit an antibody or delayed-type hypersensitivity response to HBsAg was compared for 40 paired healthy subjects, 20 per group, of whom 38 completed the vaccination protocol. The 40 subjects were allocated at random to receive three doses of 20 micrograms of vaccine intramuscularly, or three doses of 2 micrograms of vaccine intradermally. Titres of antibody to HBsAg (anti-HBs) were expressed in a radioimmunoassay by sample ratio (signal-to-noise) units (SRU). The maximal mean levels of anti-HBs (maximal one month after the third injection) were 108 SRU for the intramuscular group and 51 SRU for the intradermal group, and the levels for the intramuscular group were significantly higher at all other time-points. The levels of anti-HBs declined equally with time over 18 months in both groups. More subjects in the intramuscular group (17 of 19 subjects) showed a response to anti-HBs than in the intradermal group (14 of 19 subjects). Non-respondents in either group responded with similar frequency to further intramuscularly-administered vaccine. The frequency of delayed-type hypersensitivity to HBsAg was similar for both groups. Thus, immunization with HBsAg, when administered intradermally in a dose that is one-tenth of that recommended for intramuscular administration, induces an immune response in healthy subjects. However, since the level of antibody is lower than that after intramuscular injection, revaccination might be needed at more frequent intervals.

Adult↗
PubMed1987

Fluctuations in the expression of a glycolipid antigen associated with differentiation of melanoma cells monitored by a monoclonal antibody, Leo Mel 3.

A monoclonal antibody, Leo Mel 3, raised against a melanoma cell line (LiBr), binds to a carbohydrate determinant of cell surface gangliosides, the simplest of which is GD3. This monoclonal antibody was screened for by its capacity to block the recognition and lysis of the melanoma cells by cytotoxic T-lymphocytes with anomalous killer cell function, illustrating a novel approach for identifying monoclonal antibody to biologically relevant tumor-associated antigens. Leo Mel 3 reacted selectively with melanoma cells by indirect immunofluorescent and immunoperoxidase staining; it reacted with tissue from all primary and metastatic melanoma tested, and it bound to cells from all but one of six cultured melanoma cell lines. Leo Mel 3 did not react with a variety of carcinomas, lymphomas, leukemias, and other neuroectodermal tumors, nor with adult or fetal tissues, except fetal liver. Very weak staining of cutaneous basal melanocytes was noted in a minority of skin sections, and 50 to 80% of melanocytes in four of seven benign nevi showed weak to moderate reactivity. The antibody was relatively specific for human adherent melanoma cells, since it did not bind to the adherent murine B16 melanoma line nor to a nonadherent human melanoma cell line (PMC-22). Expression of the Leo Mel 3-defined antigen was unrelated to changes in cell cycle. When cells from an adherent melanoma cell line were detached and maintained briefly in suspension culture, the cells became markedly less reactive with Leo Mel 3 and, after readherence to plastic, they rapidly reexpressed higher levels of the ganglioside antigen; since Leo Mel 3 prevented attachment and growth of melanoma cells in vitro, a functional role for the ganglioside is suggested in cell adhesion and metastasis. Differentiation of melanoma cells with dimethyl sulfoxide, retinoic acid, and theophylline resulted in a marked and selective increase in the amount of Leo Mel 3-defined antigen, together with an increase in the target cell binding ability of these cells, assessed by cold target competition assays using anomalous killer cells.

Antibodies, Monoclonal↗
PubMed1987

Deficiency of the suppressor inducer subset of T lymphocytes in rheumatoid arthritis.

New monoclonal antibodies allow CD4 lymphocytes to be categorized into helper/inducer (HI) CD4+ 4B4+, and suppressor inducer (SI) CD4+ 2H4+ subpopulations. Blood and synovial lymphocytes from 30 patients with rheumatoid arthritis (RA), 13 patients with other articular diseases, and 24 control subjects were exposed to these monoclonal antibodies and analyzed by flow cytometry. CD4:CD8 ratios were similar for the 3 groups. In RA patients, there was a depletion of SI cells in blood and synovial fluid, and the ratio of HI cells to SI cells was elevated, particularly in the synovial lymphocytes. These data provide new evidence for T cell dysregulation in the perpetuation of RA.

Adult↗
PubMed1987

Evidence for local synthesis of antibodies to denatured collagen in the synovium in rheumatoid arthritis.

Synovial fluid samples from 36 patients with rheumatoid arthritis (RA) and 31 patients with other articular diseases (OAD) were examined for the presence of antibodies to denatured or native human type II collagen. Levels of IgG antibodies to denatured or native human type II collagen, rheumatoid factor, immunoglobulins, and total proteins were assessed in paired samples of serum and synovial fluid from 21 patients with RA and from 14 patients with OAD. Solid-phase radioimmunoassay showed that levels of antibodies to denatured collagen in synovial fluid were significantly higher in RA patients than in OAD patients (median 3,270, range 44-16,816 versus median 919, range 119-5,814; P less than 0.001). These antibody levels were higher in synovial fluid than in the serum of RA patients, but not in patients with OAD. Paired serum and synovial fluid samples showed no correlation between the level of antibodies to denatured collagen and levels of either IgG, IgA, IgM, or rheumatoid factor. Synovial fluid antibodies to native collagen were higher in RA patients. Antibodies to collagen may be synthesized preferentially in synovial tissues and, hence, participate in the perpetuation of RA.

Adult↗
PubMed1987

Familial hairy cell leukemia.

A mother and son are reported who both developed hairy cell leukemia. The mother aged 74 presented with pancytopenia and responded well to splenectomy. Four years later her son aged 48 presented with pancytopenia; splenectomy was less effective but he improved after treatment with interferon-alpha. Histological examination of the splenic tissue in both cases showed changes characteristic of hairy cell leukemia. This is the third report of this rare disease occurring in family members.

Aged↗
PubMed1987

Epstein-Barr virus as an etiological agent in primary Sjögren's syndrome.

It is proposed that the initiating event in primary Sjögren's syndrome is infection with Epstein-Barr virus (EBV), and that the autoimmune exocrinopathy that progresses to keratoconjunctivitis sicca and xerostomia is a sequel to this. Our hypothesis is based on the findings that the antinuclear antibody, anti-La(SS-B), is a marker of primary Sjögren's syndrome, and that anti-La reacts with a ribonucleoprotein, the La autoantigen, to which bind not only all cellular RNAs transcribed by RNA polymerase III, but also the viral RNAs, EBER 1 and EBER 2, encoded by the Epstein-Barr virus (EBV). It is proposed that during EBV infection, there are multiple copies of the EBERs available to bind to the La ribonucleoprotein and when infection occurs in subjects who have an impaired T cell-mediated response to EBV, and who are genetically predisposed to autoimmunity, there is loss of immunological tolerance to La with production of anti-La (SS-B). Thus the inflammatory process in exocrine glands which culminates in the sicca syndrome is due to the combined effects of chronic EBV infection and autoimmunity. Two patients are briefly described in whom primary Sjögren's syndrome appeared to be a direct consequence of EBV infection. The hypothesis engages the question of the respective roles of virus infection, specific immunodeficiency to virus, immunogenetic constitutive influences and an autoimmune response to a ribonucleoprotein antigen in the genesis of a particular organ-specific inflammatory reaction.

Antibodies, Viral↗
PubMed1987

Paraproteinemias in homosexual men with HIV infection. Lack of association with abnormal clinical or immunologic findings.

During a prospective immunologic study of 130 homosexual men, the authors looked for the presence of paraprotein bands in serum by electrophoresis. Antibody to the human immunodeficiency virus (HIV) was present in 65 of the 130 men, the lymphadenopathy syndrome (LAS) in 26, and the acquired immune deficiency syndrome (AIDS) in 3. Abnormal bands were detected in the serum of six men, as single paraproteins in four and as oligoclonal bands in two. All six were seropositive for anti-HIV; one has LAS, two had persistent but minor lymphadenopathy, and three were apparently normal. There was no significant difference between the T-cell subsets or ratios between those seropositive men with or without paraproteins. This high incidence of paraproteins is another accompaniment of B-cell hyperactivation in persons infected with HIV.

AIDS-Related Complex↗
PubMed1987

Acute scleroderma in stable mixed connective tissue disease: treatment by plasmapheresis.

This report describes a case of stable mixed connective tissue disease (MCTD) with development of acute scleroderma with hypertension, oliguric renal failure, microangiopathic hemolytic anemia, and pulmonary infiltrates. The renal histology in the acute episode was that of scleroderma with intimal sclerosis and 'onion skinning' of vessels and glomerular ischemic injury but with no evidence of damage by immune complexes either histologically or by immunofluorescence. improvement occurred after treatment with plasmapheresis, cyclophosphamide, and captopril with return of near normal renal function.

Acute Disease↗
PubMed1987

Autoantibody to aldolase in acute and chronic hepatitis.

Sera from 82 patients with acute or chronic hepatitis and 40 chronic carriers of hepatitis B were examined by ELISA and immunoblotting for reactivity with the glycolytic enzyme aldolase. The results of the ELISA tests, expressed as a percentage of a positive control, were compared to those obtained with sera from 39 patients with rubella, 11 with cytomegalovirus infection and 74 healthy subjects. The ELISA reaction with sera, expressed as mean +/- standard deviation was, for 15 patients with hepatitis A, 58.3 +/- 20.5%; 15 with hepatitis B, 59.5 +/- 42.18; 23 with hepatitis non-A, non-B 51.1 +/- 34.4%; 11 with HBsAg positive chronic active hepatitis, 70.1 +/- 31.5%; and 17 with autoimmune chronic active hepatitis, 66.8 +/- 21.4%. All values were significantly (p less than 0.05-p - less than 0.001) higher than those obtained with sera from carriers of hepatitis B surface antigen, 25.6 +/- 27.2%; rubella, 21.1 +/- 20.0%; cytomegalovirus infection, 19.2 +/- 27.8%; or healthy subjects, 20.9 +/- 16.2%. In two randomly selected sera, reactivity with aldolase by ELISA was neutralized by absorption with the enzyme. Selected sera showing reactivity by ELISA reacted by immunoblotting with aldolase. The findings suggest that acute or chronic liver damage may provoke the production of autoantibodies to aldolase.

Acute Disease↗
PubMed1987

Potentiation of delayed-type hypersensitivity by pertussigen or cyclophosphamide with release of different lymphokines.

The effects of lymphokine production of two agents known to potentiate delayed-type hypersensitivity (DTH), pertussigen (pertussis toxin) (PT) and cyclophosphamide (CY) have been investigated. These two agents were administered to immunized mice. Subsequently, lymph nodes and spleen cells were exposed to specific antigen in vitro. The resulting culture supernatants were assayed for the presence of lymphokines. Only supernatants of cells from the mice given PT contained appreciable quantities of interferon-gamma (IFN-gamma) and stimulated cells of the monocyte-like WEHI-265 cell line to produce procoagulant activator and plasminogen activator. On the other hand, CY was more effective than PT on the production of interleukin-3 (IL-3). Both adjuvants had small enhancing effects on the production of interleukin-2 (IL-2). With either adjuvant, the cell populations induced had a similarly enhanced capacity to transfer DTH. These results demonstrate that the capacity of cells to transfer DTH does not necessarily correlate with their release of particular lymphokines. The potentiation of DTH by cyclophosphamide did not depend on significantly enhanced generation of IFN-gamma, procoagulant activator, or plasminogen activator. The amount of IFN-gamma in the culture supernatants correlated with their capacity to produce procoagulant activator and plasminogen activator, whereas the amount of IL-2 and IL-3 did not.

Adjuvants, Immunologic↗
PubMed1986

Pertussigen in vivo enhances antigen-specific production in vitro of lymphokine that stimulates macrophage procoagulant activity and plasminogen activator.

Pertussigen is a protein toxin of Bordetella pertussis that acts as a powerful stimulator of the intensity and duration of delayed-type hypersensitivity (DTH) in mice. This study describes the potent in vivo effect of pertussigen on the levels of antigen-specific macrophage-activating lymphokine(s); lymphokine(s) was measured by the stimulation of macrophage procoagulant activity (mPCA), or plasminogen activator (PA) activity. Lymphoid cells were removed from immunized animals and cultured with specific antigen, keyhole limpet hemocyanin, ovalbumin, or human gamma-globulin. The culture supernatants were then incubated with the monocyte-like cell line WEHI-265 to measure mPCA or with WEHI-265 or resident peritoneal macrophages to measure PA activity. Mice were given pertussigen at the time of immunization, and the subsequent generation by lymphocyte supernatants of both of these macrophage activities proved to be greatly enhanced; the effect of pertussigen was antigen specific. Pertussigen thus induces an increase in lymphokine(s) production responsible for the in vitro increase in macrophage mPCA and PA activity and which may be responsible for some of the potent immune effects of this agent in vivo.

Animals↗