Investigation of rheumatic and connective tissue diseases.
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Biomedical subjects
Publications and source records attributed to J V Wells.
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The data indicates that Papuans with the Austronesian haplotype Gmf,a;b produce significantly higher levels of tetanus specific antibody, than Papuans without this haplotype, suggesting that response to tetanus toxoid in man is associated with the Gm phenotype of the individual. Km (1) status was not related to response.
In vivo anti-nuclear antibody (ANA) was observed by direct immunofluorescence microscopy in epithelial cell nuclei in forty-four biopsies from thirty-three patients. The tissue containing the ANA was macroscopically normal in twenty-seven patients. The thirty-three patients with in vivo biopsy ANA included twenty-three with SLE, three with mixed connective tissue disease, two each with multi-system Sjögren's syndrome, dermatomyositis, and progressive systemic sclerosis, and one with rheumatoid arthritis. Features of sicca syndrome were noted in seventeen patients. The patterns of the in vivo biopsy ANA in the thirty-three patients were speckled (21), homogeneous (6), nodular (2), and both speckled and homogeneous (4). Complement was not detected in the epithelial cell nuclei. Immunoglobulin(s) and/or complement were deposited along the dermoepidermal junction in thirty-two of the forty-four biopsies, and in dermal blood vessels in twenty-two biopsies. Each patient had serum ANA against rat liver substrate; twenty-seven had high titre ANA (1 in 1000 or greater). Elevated levels of DNA-binding were found in twenty patients (61%), but the level of DNA-binding did not correlate with the intensity of in vitro biopsy ANA staining. Serum antibody to ribonucleoprotein (RNP) was present in eight of the twenty-three patients tested (35%), all eight patients having clinical features of sicca syndrome. Hypocomplementaemia was found in thirteen patients (40%), all of whom had active SLE. In vivo biopsy ANA appears to be a real phenomenon of unknown aetiology, and not an artifact, which is found in some patients with active multisystem autoimmune disease, especially SLE.
IgA secretion and intracellular IgA synthesis by PWM-stimulated peripheral blood lymphocytes from normal and IgA deficient subjects were measured by radioimmunoassay. Cultured lymphocytes from eleven out of twelve IgA deficient subjects had impaired or undetectable IgA production. Measurement of intracellular IgA showed that the defect was more basic than simply defective secretion by IgA plasma cells. Co-culture of lymphocytes from IgA deficient and normal subjects revealed defects in both the B and T cell populations of IgA deficient subjects. In one subject the defect was in the T cells, in another the B cells, and in two others both T and B cells were defective.
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This study was designed to answer the question, do molecules with carcinoembryonic antigen (CEA) activity from colon, breast, and ovarian cancer differ? Extracts of two breast and three ovarian cancers with CEA activity were compared to three colon cancer CEA preparations and to the related antigen, colon carcinoma antigen-III, in terms of lectin- and antiserum-binding properties. With the use of Farr-type radioimmunoassays with the lectins, concanavalin A and wheat germ agglutinin, the iodinated colon CEA and CEA-like preparations from breast and ovarian cancer all showed distinctly different patterns of binding. Specificity of binding was confirmed by inhibition studies with the relevant monosaccharides. Similarly, with antisera prepared against colon CEA, colon carcinoma antigen-III, or breast CEA, it was shown that, although all preparations shared some antigens, unique antigenic determinants were also present on all preparations. These data are consistent with the concept of a series of closely related CEA and CEA-like molecules with distinct characteristics for each tissue source of CEA.
Several antibodies have been reported in selective IgA deficiency and we have detected antibodies to human IgM and native human collagen in 35 and 34%, respectively, of 60 such subjects (compared to 1.6 and 2.0%, respectively, in normal controls). The anti-IgM isoantibodies are clearly distinguishable from antibodies to ruminant proteins and there was no statistically significant association between different antibodies and clinical features in individual patients. The etiology of the antibodies remains unknown.