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Biomedical subjects

R A Joske

Publications and source records attributed to R A Joske.

At least 19 recordsLinked to original sources
PubMed1990

Autoantibodies to isolated human hepatocyte plasma membranes in chronic active hepatitis. II. Specificity of antibodies.

The fine specificity of autoantibodies to human hepatocyte plasma membranes in autoimmune chronic active hepatitis was determined by one-dimensional immunoblotting. Sera from 12 patients with "classical" autoimmune chronic active hepatitis contained autoantibodies recognizing many human hepatocyte plasma membrane polypeptides in the 15 to 220 kD range. Many of these autoantibodies titrated beyond 1:80,000 and some may be potentially "pathological." In particular, one band with an apparent molecular weight of 60 kD was a dominant and consistent finding in all patients with autoimmune chronic active hepatitis by immunoblotting. Serum absorption studies showed this band to be predominantly liver-specific. Control sera from patients with chronic persistent hepatitis, nonhepatic autoimmune disease and normal healthy subjects possessed low titer reactivity that most likely represented "natural" autoantibodies. Anti-human hepatocyte plasma membranes in autoimmune chronic active hepatitis consisted of all three immunoglobulin isotypes (G,M and A) and their presence was not caused by nonspecific reactions as a consequence of hypergammaglobulinemia. Autoantibodies were shown to be specific by virtue of their absorption and exhaustion on titration. Many were directed at species nonspecific determinants, however, some autoantibodies recognized human-specific polypeptides. The majority of anti-human hepatocyte plasma membranes appeared to be organ-specific as sera from patients with autoimmune chronic active hepatitis reacted only weakly with polypeptides of kidney plasma membranes. Of the activity detected, few bands corresponded with those obtained using polypeptides of human hepatocyte plasma membranes. Our results show that patients with autoimmune chronic active hepatitis possess an array of liver-specific autoantibodies to polypeptide subunits of human hepatocyte plasma membranes.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1989

Autoantibodies to isolated human hepatocyte plasma membranes in liver disease. I. Specificity for chronic active hepatitis.

Circulating autoantibodies reacting with human hepatocyte plasma membranes (HHPM) were quantitated in acute and chronic liver disease using an enzyme-linked immunosorbent assay (ELISA). Anti-HHPM were found most frequently in patients with chronic active hepatitis (CAH), a disease postulated to result from autoimmune processes directed at organ-specific antigens on the surface of hepatocytes. The high incidence of anti-HHPM in CAH (75%) contrasted significantly with all other groups assayed, including primary biliary cirrhosis (44%), alcoholic liver disease (21%), acute viral hepatitis (17%), and chronic persistent hepatitis (8%). The titers of anti-HHPM in CAH were significantly greater than in other liver disease and control groups. Anti-HHPM quantitated by ELISA correlated with hepatocellular membrane staining by indirect immunofluorescence. Autoantibodies to HHPM were found with an equivalent frequency in three etiological subgroups of CAH: autoimmune CAH, hepatitis B virus (HBV)-related CAH, and CAH associated with excess alcohol consumption. Anti-HHPM of the IgG and IgA isotypes were found in the highest frequency. There was a trend for patients with a histologically more severe disease to have higher titers of anti-HHPM. Immunoblots of SDS-PAGE-separated HHPM showed antibodies to react with a number of polypeptides, some of which appeared human specific. These data suggest that isolated HHPM are a source of relevant hepatocellular membrane antigens. Further studies of the different antigenic specificities of anti-HHPM are required to define which of these may be of pathogenetic importance in chronic active hepatitis.

Autoantibodies↗
PubMed1988

Esophageal cancer in a young woman after treatment for osteosarcoma.

Five years after completing adjuvant chemotherapy for osteosarcoma of the fibula, a 20-year-old woman developed an esophageal carcinoma. The association between prior chemotherapy and radiation exposure, and the significance of genetic factors and family history are discussed. This case exemplifies the importance of continued follow-up of the long-term survivors of tumor management.

Adult↗
PubMed1986

Angiocentric pulmonary granulomas in tuberculosis.

An open-lung biopsy performed in a 15-year-old girl because of left sided pulmonary nodules revealed striking angiocentric necrotising granulomas. No acid fast bacilli (AFB) were cultured or demonstrated in tissue sections, however, the diagnosis of tuberculosis was suggested. Anti-tuberculous therapy resulted in both clinical and radiological cure within 12 months. The differential diagnosis of this type of lesion should include pulmonary tuberculosis as well as the non-infective angiocentric granulomas such as lymphomatoid granulomatosis and has major therapeutic implications.

Adolescent↗
PubMed1985

An enzyme-linked immunosorbent assay for the detection of hepatocyte plasma membrane antibodies.

An enzyme-linked immunosorbent assay (ELISA) using plates coated with hepatocyte plasma membranes (HPM) was developed for the measurement of antibodies directed at hepatocyte surface antigens. Precoating ELISA plates with poly-L-lysine (PLL) provided firm attachment for the adsorption of HPM. The use of HPM, in preference to whole hepatocytes, excludes pathologically irrelevant cytoplasmic antigens. In addition, there is no necessity for glutaraldehyde fixation which is commonly used in cellular assays to maintain cellular integrity and which may result in loss or alteration in antigenic specificities. The assay was used to study loss of tolerance to mouse HPM in mice immunized with rat HPM. Three mouse strains were immunized, each strain developed antibodies to rat HPM and autoantibodies to mouse HPM with autoantibody levels reaching a peak 6-10 weeks after commencement of immunization. The correlation between ELISA and indirect immunofluorescence for the measurement of HPM autoantibodies was 0.79 (P less than 0.001) within the serum titration range of 1:25 to 1:200. Antibody to control kidney plasma membrane (KPM) was also measured by ELISA, after elimination of endogenous alkaline phosphatase activity using levamisole. Immunization with rat HPM elicited organ-non-specific autoantibodies to KPM, but these were at lower levels than autoantibodies to HPM.

Alkaline Phosphatase↗
PubMed1984

Autoantibody to liver-specific lipoprotein in the mouse: regulation by naturally occurring autoantigen specific suppressor cells.

Indirect and direct evidence is presented that normal, non-immune mice have cells which suppress antibody production to murine liver specific lipoprotein (LSP) autoantigens with little or no effect on the response to a closely related foreign antigen complex, rabbit LSP. Suppressor control mechanisms were suggested in low responder BALB/c mice which produced LSP autoantibody only after exposure to low dose X-irradiation or treatment with cyclophosphamide. Adoptive transfer experiments in X-irradiated BALB/c mice and untreated C57BL/6 mice showed that cells from normal mouse spleen prevented LSP autoantibody production when put into the circulation of mice prior to immunization with foreign rabbit LSP. This suppressor activity was destroyed by treatment with antisera to T cells and by low dose X-irradiation. The normal spleen cells were ineffective as suppressors if given after primary immunization with rabbit LSP had commenced. It is suggested that the adoptive transfer of normal spleen cells prior to immunization with foreign LSP supplements homeostatic mechanisms in favour of tolerance to LSP autoantigen. It is argued that the LSP autoantibody response in the mouse is a unique model for the study of autoantigen specific naturally occurring suppression.

Animals↗
PubMed1983

Autoantibodies to liver-specific lipoprotein following hepatitis induced by mouse cytomegalovirus.

Autoantibodies to liver specific lipoprotein (LSP) are produced following acute non-fatal hepatitis in murine cytomegalovirus (MCMV) infected mice. Both C57B1 and BALB/c mice produced a transient LSP autoantibody response demonstrated by passive haemagglutination and enzyme linked immunosorbent assay. C57Bl mice produced both IgM and IgG LSP autoantibody and BALB/c mice produced only IgM autoantibody. The autoantibody was species non-specific, reacting with both mouse and rabbit LSP. Plasma containing LSP autoantibody reacted with the surface of normal mouse hepatocytes by immunofluorescence. This model provides an opportunity for study of LSP autoantibody production during viral hepatitis.

Animals↗
PubMed1981

Autoantibody responses to liver-specific lipoprotein in mice.

Autoantibody to the hepatocyte membrane antigen, liver-specific lipoprotein (LSP) was induced in mice by immunization with LSP-containing protein preparations from human, rat, rabbit and mouse liver and also with purified allogeneic LSP. Each of the strains of mice used (C57B1, BALB/c, C3H) showed the capacity to produce high titre autoantibody to LSP. Autoantibody to LSP demonstrated by passive haemagglutination was absorbed by normal mouse hepatocytes but not by kidney or spleen cells and reacted with the cell membrane of normal mouse hepatocytes by immunofluorescence. The liver was examined histologically in all mice and where inflammation was found it was attributable to the Freund's complete adjuvant used in immunization rather than liver protein immunogen. The demonstration of high titre autoantibody to LSP in mice without associated hepatitis contrasts with chronic hepatitis in man and experimental chronic hepatitis in rabbits where autoantibodies to LSP have been implicated in the pathogenesis of the disease.

Animals↗
PubMed1980

Epidemiology of chronic hepatitis in Perth, Western Australia.

A survey was made on 50 patients with active chronic hepatitis (ACH) seen in Perth, Western Australia. The aetiology varied: three cases followed metabolic disease, 8 drugs or alcohol, 12 were due to hepatitis B and no cause in 27. There was a male preponderance in the first three groups and a female preponderance in the idiopathic group. The drug dependent group had a greater mean age than the other groups. Autoantibodies were present in 40 of the cases--the most frequent were antismooth muscle antibody in 24 cases and antinuclear factor in 13 cases. Six patients (12%) improved and are well following discontinuation of therapy. Seven (14%) have died. The rest (74%) remain on treatment.

Adolescent↗
PubMed1979

Incidence and etiology of primary liver cancer in the Pacific Basin.

The incidence of PLC in the Pacific Basin varies from 0.9/100,000 (age-standardized) in women in New South Wales, Australia, to 34.2/100,000 in Singapore Chinese men. Proportional incidence data suggest that other areas of the Pacific Basin, such as Hong Kong, Taiwan, Indonesia, and Papua New Guinea, may have PLC incidence rates as high or higher than those in Singapore Chinese. Infection with hepatitis-B virus has been associated with PLC in some areas, and aflatoxin contamination of food has also been demonstrated. The extent to which these or other factors explain the geographical variation in liver cancer rates in the Pacific Basin is uncertain.

Adolescent↗
PubMed1978

Occurrence of large proximal splenic artery aneurysms in chronic liver disease.

Two cases are reported of large pre-splenic aneurysms of the splenic artery in patients with chronic liver disease, and three others cited from the literature. Four of the five died from rupture of the aneurysm. All patients were parous females with chronic liver disease, and in four of the five this was known to be present before pregnancy. It is suggested that proximal splenic artery aneurysms in such patients are due to both haemodynamic changes of portal hypertension and the endocrine changes of pregnancy. This concept may lead to early recognition of these lesions, although there are as yet no certain indications for investigation or surgical intervention in asymptomatic patients.

Adult↗
PubMed1976

Serum IgE levels in patients with liver disease.

IgE (reaginic antibody) levels have been estimated on 160 occasions in 120 patients with liver disease. IgE levels were significantly raised in patients with untreated active chronic hepatitis, and returned towards normal with steroid or immunosuppressive therapy. They were also increased in patients with liver disease associated with alcoholism. There were no significant alterations in IgE levels in other types of acute or chronic liver disease. There were no significant correlations between IgE levels and the age or sex of the patients and the results of other laboratory tests carried out.

Acute Disease↗