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Eng M. Tan

Bio: Eng M. Tan is an academic researcher from Scripps Research Institute. The author has contributed to research in topics: Antigen & Autoantibody. The author has an hindex of 47, co-authored 71 publications receiving 30110 citations. Previous affiliations of Eng M. Tan include University of Pittsburgh & University of Vermont.


Papers
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Journal ArticleDOI
TL;DR: The cooccurrence of autoantibodies to centromere proteins and HP1 in certain autoimmune diseases might be a reflection of coordinated immune responses to these closely associated sets of proteins.
Abstract: Some autoimmune sera containing anticentromere autoantibodies also recognize a doublet of Mr 23 000 (p23) and 25 000 (p25) in addition to CENP (centromere protein)-A (Mr 19 000), -B (Mr 80 000), and -C (Mr 140 000). A p25 antigen (HP1Hsα) has been shown to be a human homolog of Drosophila HP1 (heterochromatin protein 1). We have isolated a cDNA clone encoding another form of p25 (HP1Hsβor p25β) from a λZap HepG2 library using human autoimmune serum. The deduced amino acid sequence of the clone contained a conserved chromodomain (chromatin modifier domain) in the N-terminal region and a heterochromatin binding domain in the C-terminal region. In immunofluorescence experiments, only affinity purified antibodies reactive with the C-terminal (amino acids 70–185) domain showed nucleoplasmic and heterochromatin staining, whereas N-terminal (amino acids 1–115) specific antibodies were nonreactive. In metaphase chromosome spreads, the C-terminal domain antibody was also localized to the centromeric regions of chromosomes. Association with centromeres was most prominent at anaphase and changed to a more generalized association with whole chromosomes in telophase. The cooccurrence of autoantibodies to centromere proteins and HP1 in certain autoimmune diseases might be a reflection of coordinated immune responses to these closely associated sets of proteins.

67 citations

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TL;DR: Cytoplasmic p90 autoantigen was recently cloned from a cDNA expression library using serum antibody from a cancer patient and the humoral immune response to p90 in prostate cancer and benign prostatic hyperplasia was examined.
Abstract: BACKGROUND Cytoplasmic p90 autoantigen was recently cloned from a cDNA expression library using serum antibody from a cancer patient. The humoral immune response to p90 in prostate cancer and benign prostatic hyperplasia (BPH) was examined. METHODS An antigenic fragment of recombinant p90 protein and several other tumor-associated antigens (TAAs) were used in ELISA and Western blotting to detect antibodies in sera from patients with prostate cancer, BPH, and other controls. RESULTS Autoantibodies to p90 were detected in 30.8% of 133 prostate cancer patients versus 1.5% in 68 BPH patients. When a selected panel of six TAAs including p90 were used for immunoscreening, the cumulative positive reactions in prostate cancer sera reached 92.5%, significantly higher than in BPH and other control sera. Antibodies to p90 showed the highest frequency in prostate cancer (30.8%), followed by antibodies to p62 (22.6%). CONCLUSIONS A panel of six selected TAAs was shown to have high sensitivity and specificity as immunodiagnostic markers in prostate cancer. © 2004 Wiley-Liss, Inc.

61 citations

Journal ArticleDOI
TL;DR: The presence of a specific immune response against an enzyme that has been associated with various immunodeficiency syndromes raises intriguing possibilities concerning the relationship between DNA damage, immunodficiency, and autoimmunity.
Abstract: The chromatin-bound enzyme poly(ADP-ribose) polymerase (ADPRP) is strongly stimulated by DNA with single- or double-stranded breaks, and transfers the ADP-ribose moiety of NAD to nuclear proteins. The activation of ADPRP is important for DNA repair and replication, and also has been postulated to play a role in the pathogenesis of lymphocyte dysfunction associated with chronic inflammatory diseases, and inborn errors of nucleoside metabolism. We have detected high titers of IgG autoantibodies to the ADPRP protein in six patients with rheumatic complaints. No other autoantibodies were detected in any of the six sera. The specificity of the anti-enzyme antibodies was established by (a) immunoprecipitation of ADPRP activity, (b) immunoprecipitation and immunoblotting of both the native 116-kD enzyme and its proteolytic digestion products. ADPRP was purified from human thymus and calf thymus. The autoantibodies reacted equivalently with both enzymes. The anti-ADPRP antibodies had a distinctive immunofluorescent pattern with HEp-2 cells, reacting intensely with nucleoli and metaphase chromosomes, and diffusely with the nucleus. Autoantibodies to ADPRP have not been described previously. The presence of a specific immune response against an enzyme that has been associated with various immunodeficiency syndromes raises intriguing possibilities concerning the relationship between DNA damage, immunodeficiency, and autoimmunity.

60 citations

Journal ArticleDOI
TL;DR: These studies have revealed several key features of the nature of the ANA response that support the hypothesis that ANAs are driven by subcellular particles such as organelles or macromolecular complexes which might be in an activated or functional state, which leads to the central question of how endogenous sub cellular particles that are normally sequestered can be released from cells and exposed to the immune system in a manner that renders them capable of driving a sustained AnA response.
Abstract: Studies of antinuclear autoantibodies (ANAs) associated with systemic autoimmune diseases and their target autoantigens have revealed several key features of the nature of the ANA response. First, each systemic autoimmune disease has a characteristic ANA spectrum, suggesting that specific inciting antigens must be associated with each disease. Second, ANAs are directed against components of functionally important subcellular particles. Third, ANAs recognize highly conserved, conformation-dependent epitopes associated with active regions of the targeted subcellular particle. Fourth, ANAs often target autoantigens associated with active cell division or proliferation. These features support the hypothesis that ANAs are driven by subcellular particles such as organelles or macromolecular complexes which might be in an activated or functional state. This hypothesis leads to the central question of how endogenous subcellular particles that are normally sequestered can be released from cells and exposed to the immune system in a manner that renders them capable of driving a sustained ANA response. An emerging view is that apoptosis could be a mechanism by which potentially immunostimulatory self-antigens might be released from cells. Unregulated cell death or aberrant phagocytic clearance and presentation of debris from dying cells might facilitate the exposure to the immune system of excessive amounts of intracellular material which could potentially induce and maintain, by repeated stimulation, an ANA response.

58 citations

Journal ArticleDOI
TL;DR: The hypothesis that autoimmunity to p330d/CENP-F could be related to events involving increased or abnormal cell proliferation is pointed to.

56 citations


Cited by
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TL;DR: A method has been devised for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets that results in quantitative transfer of ribosomal proteins from gels containing urea.
Abstract: A method has been devised for the electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets. The method results in quantitative transfer of ribosomal proteins from gels containing urea. For sodium dodecyl sulfate gels, the original band pattern was obtained with no loss of resolution, but the transfer was not quantitative. The method allows detection of proteins by autoradiography and is simpler than conventional procedures. The immobilized proteins were detectable by immunological procedures. All additional binding capacity on the nitrocellulose was blocked with excess protein; then a specific antibody was bound and, finally, a second antibody directed against the first antibody. The second antibody was either radioactively labeled or conjugated to fluorescein or to peroxidase. The specific protein was then detected by either autoradiography, under UV light, or by the peroxidase reaction product, respectively. In the latter case, as little as 100 pg of protein was clearly detectable. It is anticipated that the procedure will be applicable to analysis of a wide variety of proteins with specific reactions or ligands.

53,030 citations

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TL;DR: In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries, and the presence and clinical associations or antiphospholipid antibodies in patients with SLE was suggested.
Abstract: In 1982, the Diagnostic and Therapeutic Criteria Committee of the American College of Rheumatology (ACR)published revised criteria for the classification of systemiclupus erythematosus (SLE) (1). During the ensuing decade several investigators, including Drs. Graham Hughes and Donato Alarcon-Segovia, among others, have described the presence and clinical associations or antiphospholipid antibodies in patients with SLE, as well as the occurrence of theprimary antiphospholipid syndrome (2-5). In 1992, Piette and colleagues suggested that the ACR revised criteria be reevaluated in light of the above discoveries (6).

9,999 citations

Journal ArticleDOI
TL;DR: Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes and these proposed criteria utilize classification trees, or algorithms.
Abstract: For the purposes of classification, it should be specified whether osteoarthritis (OA) of the knee is of unknown origin (idiopathic, primary) or is related to a known medical condition or event (secondary). Clinical criteria for the classification of idiopathic OA of the knee were developed through a multicenter study group. Comparison diagnoses included rheumatoid arthritis and other painful conditions of the knee, exclusive of referred or para-articular pain. Variables from the medical history, physical examination, laboratory tests, and radiographs were used to develop sets of criteria that serve different investigative purposes. In contrast to prior criteria, these proposed criteria utilize classification trees, or algorithms.

6,160 citations

Journal ArticleDOI
TL;DR: The study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice, and substitution of the Rome pain criterion for the New York pain criterion is proposed.
Abstract: The New York and the Rome diagnostic criteria for ankylosing spondylitis (AS) and the clinical history screening test for AS were evaluated in relatives of AS patients and in population control subjects. The New York criterion of pain in the (dorso) lumbar spine lacks specificity, and the chest expansion criterion is too insensitive. The Rome criterion of low back pain for more than 3 months is very useful. Our study showed the clinical history screening test for AS to be moderately sensitive, but it might be better in clinical practice. As a modification of the New York criteria, substitution of the Rome pain criterion for the New York pain criterion is proposed.

5,143 citations