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Biomedical subjects

E M Tan

Publications and source records attributed to E M Tan.

342 records · Page 19Linked to original sources
PubMedDate not supplied

Serum antibody in rheumatoid arthritis reactive with a cell-associated antigen. Demonstration by precipitation and immunofluorescence.

A cell-free extract of human diploid B lymphocytes (Wil2) in continuous culture was used as the source of antigen in immunodiffusion to detect a precipitating antibody referred to as rheumatoid arthritis precipitin (RAP) in sera of patients with rheumatoid arthritis (RA). The prevalence of RAP was determined in various arthritides and other connective tissue diseases. It was found in 67% of patients with seropositive RA and in 62% of patients with Sjögren's syndrome associated with RA. But its frequency was lower in many other connective tissue diseases, including seronegative RA and Sjögren's syndrome without associated RA. Matching sera and synovial fluids from patients with seropositive RA were also studied. Differences in serum and synovial fluid RAP titers were demonstrated, but generally when RAP was present in serum, it was also present in synovial fluid and vice versa. Indirect immunofluorescence (IF) with Wil2 cells as substrate was used to demonstrate RAP and to determine morphologically the nature of the reactive cellular antigen. When cells were treated with commonly used fixatives, little or no staining with RAP positive sera was observed. This outcome was shown to be the result of the extreme solubility of the cellular antigen reactive with RAP. The antigen was retained best in a reactive form in Wil2 cells after fixation of cells with dry heat at 37 degrees C for 30 minutes, and it was demonstrated by IF staining as small round granules distributed in the nucleus and cytoplasm. IF was also employed to demonstrate that RAP is immunoglobulin belonging to IgG and IgM classes and not to IgA or IgD.

Antibodies↗
PubMedDate not supplied

Differentiation and characterization of autoantibodies and their antigens in Sjögren's syndrome.

Autoantibodies in Sjögren's syndrome (SS) were identified by their precipitin reactions with tissue antigens in immunodiffusion. The source of antigens was a sonicated extract of human lymphoid cells (WiI2) grown in tissue culture. Three distinct precipitin systems were identified and referred to as precipitins SS-A and SS-B, and rheumatoid arthritis precipitin. These studies show that precipitins SS-A and SS-B are present in high frequency in sera of patients with SS without associated rheuamtoid arthritis (RA) and are absent or present in low frequency in many other connective tissue diseases. On the other hand patients with SS who also had clinical features compatible with RA (SS-RA) did not have precipitins SS-A and SS-B but had rheumatoid arthritis precipitin (RAP). The latter precipitin was also present in RA patients in a similar order of frequency as in SS-RA. All three precipitin systems were shown to be reactions betweeen immunoglobulins and cellular antigens. The origin of SS-A and SS-B antigens was demonstrated by immunofluorescence to be primarily from the nucleus but the origin of RAP in the cell has not been established.

Antigen-Antibody Reactions↗
PubMedDate not supplied

Identification of antibodies to nuclear acidic antigens by counterimmunoelectrophoresis.

Saline extracts of rabbit thymus were found to contain many nuclear antigens that reacted with antibodies in the sera of patients with systemic rheumatic diseases. Counterimmunoelectrophoresis (CIE) was used to detect antibodies to nuclear acidic protein (Sm), nuclear ribonucleoprotein (RNP), and antibody to nuclear antigen B, which was reported previously in Sjögren's syndrome. All these nuclear antigens behaved as anions with different mobilities in CIE and could be distinguished from one another by the locations of the precipitin lines. They could also be distinguished by the facts that the nuclear RNP precipitin lines were abolished by digestion with ribonuclease whereas others were unaffected, and that Sm precipitin lines developed later than other precipitin lines. With this technique antibody to nuclear RNP was detected in 46% of patients with systemic lupus erythematosus (SLE) compared to 26% detected by the hemagglutination technique. Similarly the increased sensitivity of the CIE technique was able to show that antibody to B antigen was present in 12% of SLE patients, whereas this antibody was not detectable in the same group of patients by immunodiffusion. This study shows that CIE is a rapid and sensitive technique for detecting precipitating antibodies to a number of nuclear acidic antigens. Methods are described to identify the immunochemical specificities of the precipitin lines by the use of standard reference sera.

Antibodies, Antinuclear↗
PubMedDate not supplied

Association between the nucleolus and the coiled body.

By means of light and electron microscopic immunocytochemistry, we have localized p80-coilin, a specific protein marker for coiled bodies, in mammalian cell lines as well as in primary rat neuron cultures. p80-coilin-stained nuclear bodies, which also contained fibrillarin, could be subsequently silver stained by a method specific for the visualization of nucleolar organizer regions. In cycling cells, most coiled bodies were not associated with nucleoli, whereas in rat neurons such as association was frequent. The treatment of cycling cells with actinomycin D or 5,6-dichloro-1-beta-D-ribo furanosyl-benzimidazole led to nucleolar segregation and/or disintegration, and to an association of p80-coilin staining structures with nucleoli. p80-coilin-positive structures contained fibrillarin in both untreated and treated cells. These results support the opinion that there might be a special association between coiled bodies and nucleoli, particularly in neuronal cells.

Animals↗
PubMedDate not supplied

The possible role of Epstein-Barr virus in rheumatoid arthritis.

The sera of patients with rheumatoid arthritis form a precipitate with an antigen present in the sonicate of a human B (bone marrow-derived) lymphoid cell line (WiL2). The antibody is distinct from rheumatoid factor. The antigen can be demonstrated by an immunofluorescence technique to be distributed within the nucleus of the WiL2 cell and shows a discrete speckled pattern of nuclear staining. The nuclear antigen is not detectable in organ extracts from many animal species or in human T (thymus-derived) lymphoid cell lines. The current evidence suggests that the nuclear antigen is detectable only in human B lymphoid cells infected with Epstein-Barr virus. It is not clear at present whether the nuclear antigen is a viral protein or a cell protein induced by the Epstein-Barr virus as a result of polyclonal B cell activation.

Antibodies, Antinuclear↗
PubMedDate not supplied

Steroid-induced dermal atrophy: effects of glucocorticosteroids on collagen metabolism in human skin fibroblast cultures.

Collagen production by human skin fibroblast cultures was studied by incubation with [3H] proline and several glucocorticosteroids known to produce dermal atrophy in vivo. Collagen production was measured as formation of [3H]hydroxyproline or collagenase-digestible 3H-polypeptides, and the values were corrected for changes in cell number in the same cultures. The steroids, in a wide concentration range, failed to elicit any consistent alterations in collagen production. Review of the literature dealing with corticosteroid-induced changes in collagen production by human skin fibroblasts indicate conflicting results even under apparently similar incubation conditions. Consequently, no unifying hypothesis for steroid-induced dermal atrophy can be developed presently based on the in vitro data.

Cell Count↗
PubMedDate not supplied

Autoantibodies in scleroderma.

In scleroderma a profusion of circulating autoantibodies have now been defined. They include autoantibodies to Scl-70 or DNA topoisomerase 1, and to centromere/kinetochore proteins of 17.80 and 140 kilodaltons. In addition, there are several antigens which are resident primarily in the nucleolus and they are RNA polymerase 1, PM-Scl, fibrillarin and 7-2 ribonucleoprotein. Antibody to Scl-70 has been found primarily in the diffuse form of scleroderma and antibody to the centromere/kinetochore proteins in the CREST (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly and telangiectasia) subset of scleroderma. Autoantibodies to the nucleolar antigens RNA polymerase 1, PM-Scl, fibrillarin and 7-2 RNP have been detected in at least 10% of all patients with scleroderma. For several reasons which are discussed, it appears that the autoantibody response in scleroderma is antigen-driven and further that the autoantigens involved in this disease are present at some time in the nucleolus. These observations may be providing clues to some of the basic mechanisms initiating autoimmunity.

Autoantibodies↗
PubMedDate not supplied

Microvascular abnormalities as possible predictors of disease subsets in Raynaud phenomenon and early connective tissue disease.

In vivo capillary examination was performed on 80 patients included in a prospective study of Raynaud phenomenon (RP): 40 RP only (RPO), 20 undifferentiated connective tissue disease (UCTD) and 20 systemic scleroderma (SD) of less than 5 years' duration. On initial examination, SD-pattern capillary abnormalities were found in 7/40 patients with RP alone, 18/20 with UCTD and 19/20 with SD. On follow-up a change of diagnosis into a definite connective tissue disease occurred in 4 patients with UCTD; one patient with RP alone died with symptoms of myositis and fulminant pulmonary vasculitis. All five showed SD-pattern capillary abnormalities of the "active" type on initial examination. A significant correlation between the "slow" capillary pattern and the presence of anticentromere antibodies was also observed. Only one patient of 25 RPO with normal capillaries available for follow-up showed any change in clinical status.

Antibodies, Antinuclear↗
PubMedDate not supplied

Autoantibody-defined epitopes on nuclear antigens are conserved, conformation-dependent and active site regions.

Antinuclear antibodies in the systemic rheumatic diseases have been powerful reagents for identifying and characterizing nuclear antigens and for elucidating immune mechanisms which drive the autoimmune response. Concepts which have emerged from these studies include the following: the autoimmune response is antigen driven, autoantigens are components of subcellular particles, autoantigens are involved in important biosynthetic functions and epitopes recognized by autoantibodies are active sites or functional domain regions. PCNA (proliferating cell nuclear antigen) is a nuclear protein of 36 kDa and autoantibodies are present in patients with systemic lupus erythematosus. PCNA is a component of the DNA replication complex and is associated with DNA polymerase delta in continuous strand DNA synthesis at the replication fork. Studies have shown that epitopes on PCNA recognized by lupus antibodies are conformation-dependent. Composite peptides synthesized by joining discontinuous linear sequences were used to immunize rabbits and one such composite peptide induced antibodies with properties strikingly similar to human autoantibodies. Immunogens in the systemic autoimmune diseases are likely to be intranuclear or other intracellular particles composed of protein-protein or protein-nucleic acid complexes which are involved in cellular biosynthetic functions.

Antigens, Nuclear↗