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Biomedical subjects

E M Tan

Publications and source records attributed to E M Tan.

At least 235 records · Page 13Linked to original sources

The incidence of Sjögren's sicca complex in a population of patients with keratoconjunctivitis sicca.

A prospective study was performed on patients who came to a university ophthalmology outpatient clinic with the complaint of dry eyes and who were documented to have keratoconjunctivitis sicca (KCS). Of 45 patients studied 1 had primary amyloidosis, and another 10 had KCS with a previously diagnosed connective tissue disease. Of the remaining 34 patients, 19 had KCS alone without xerostomia, and the remaining 15 had KCS in association with subjective or objective xerostomia. Eight of these 15 patients were subsequently shown to have clinical Sjögren's syndrome--sicca complex, and for the majority, serologic and biopsy findings supported this diagnosis.

Adult↗

The 1982 revised criteria for the classification of systemic lupus erythematosus.

The 1971 preliminary criteria for the classification of systemic lupus erythematosus (SLE) were revised and updated to incorporate new immunologic knowledge and improve disease classification. The 1982 revised criteria include fluorescence antinuclear antibody and antibody to native DNA and Sm antigen. Some criteria involving the same organ systems were aggregated into single criteria. Raynaud's phenomenon and alopecia were not included in the 1982 revised criteria because of low sensitivity and specificity. The new criteria were 96% sensitive and 96% specific when tested with SLE and control patient data gathered from 18 participating clinics. When compared with the 1971 criteria, the 1982 revised criteria showed gains in sensitivity and specificity.

Arthritis↗

Assay of collagenase activity by a rapid, sensitive, and specific method.

A new method for the assay of collagenase activity has been developed, whereby the collagen cleavage products, after initial collagenase digestion, are degraded further by a mixture of trypsin and alpha-chymotrypsin. The degradation products are soluble in TCA and can be conveniently separated from the remaining uncleaved collagen substrate by rapid filtration. The enzyme assay is shown to be reproducible and sensitive, and it lends itself to a convenient and rapid determination of collagenase activity in relatively large numbers of samples. The applicability of this method is demonstrated by the detection of increased collagenase activity in skin fibroblast cultures derived from a patient with recessive dystrophic epidermolysis bullosa.

Bacteria↗

Inhibition of collagen accumulation in fibrotic processes: review of pharmacologic agents and new approaches with amino acids and their analogues.

Accumulation of collagen is the major pathologic feature in a variety of fibrotic processes, including dermal fibrosis in progressive systemic sclerosis, morphea, familial cutaneous collagenoma, connective tissue nevi of the collagen type and in keloids. Recent advances in the biochemistry of collagen have allowed us to define specific levels of collagen biosynthesis and degradation at which a pharmacologic intervention can lead to reduced collagen deposition. In this review, we are discussing the mechanisms of action by some of the therapeutic agents currently in use. We further present some new developments involving amino acids and their analogues which could potentially provide us with novel means to reduce the excessive accumulation of collagen in dermal fibrotic processes.

Amino Acids↗

A solid-phase radioimmunoassay for anti-histone antibodies in human sera: comparison with an immunofluorescence assay.

A solid-phase assay for anti-histone antibodies is described, in which antibodies bound to calf thymus total histones, specific histone classes, or chromatin were detected by radioactive anti-human IgG, IgA or IgM. The reactivity of human sera from various rheumatic diseases was analyses by this assay and compared with results obtained from an indirect immunofluorescence assay (FANA) previously described. Sera that were positive in the FANA assay were usually positive in the solid-phase assay when total histones were the solid-phase antigen. However, many sera had IgM antibodies to total histones in the solid-phase assay but gave no detectable reaction in the FANA assay. Results from the solid-phase assay, using individual histones and chromatin, showed that the anti-histone antibodies in these sera were predominantly reactive with histones H3-H4 and did not bind well to histones complexed to DNA in the form of chromatin.

Animals↗

Association of antinuclear and antinucleolar antibodies in progressive systemic sclerosis.

Antinuclear and/or antinucleolar antibodies were demonstrated in the sera of 74 of 76 patients (97%) with progressive systemic sclerosis, using tissue culture cells (HEp-2) as substrate in the indirect immunofluorescent method. Six patterns of nuclear staining and three nucleolar patterns were recognized. The nuclear patterns were centromere, fine speckles, coarse speckles, diffusely grainy, homogeneous and nuclear dots. The nucleolar patterns were speckled, homogeneous and clumpy. The results of digestion studies with ribonuclease, deoxyribonuclease and trypsin suggested that the nuclear antigens are proteins, some of which may be associated with chromatin. The nucleolar antigens appeared to be nucleic acid in nature. Certain characteristic serologic and clinical features associated with staining patterns were observed. The diffusely grainy pattern was seen only in sera containing antibody to Scl-70 antigen. Centromere staining was confirmed to be highly selective for the CREST (Calcinosis, Raynaud's phenomenon, esophageal involvement, sclerodactyly and telangiectasis) variant of progressive systemic sclerosis with rheumatoid factor titres higher in these patients with anti-centromere antibodies.

Adult↗

A nuclear antigen associated with cell proliferation and blast transformation.

A nuclear antigen associated with cell proliferation (proliferating cell nuclear antigen-PCNA) and blast transformation is recognized by autoantibodies in the sera of some patients with systemic lupus erythematosus. This autoantibody is a precipitating antibody and also reacts in immunofluorescence, staining the nucleoplasm of proliferating and blast-transformed cells. The autoantibody was used as a reagent to determine the distribution of PCNA in a synchronized continuous B lymphoid cell line (WiL-2) and in mitogen-induced blast-transformed lymphocytes. In WiL-2 cells, PCNA was detected as speckled nucleoplasmic staining in G1, S, and G2 phases of the cell cycle. In addition, during late G1 and early S phases, PCNA was also detected in the nucleolus. During mitogen-induced blast transformation of lymphocytes, PCNA was noticed in the nucleolus before the initiation of DNA synthesis and later became nucleoplasmic with disappearance of nucleolar staining. These studies demonstrate that the relationship of PCNA to proliferation and blast transformation may be associated with events related to DNA synthesis in these cells.

Animals↗

Serologic studies in patients with keratoconjunctivitis sicca.

Thirty-two patients with keratoconjunctivitis sicca (KCS) were screened for the presence of antinuclear antibodies, rheumatoid factor, and autoantibodies associated with Sjögren's syndrome (designated SS-A and SS-B). None of these patients had or were found to have clinical evidence of connective-tissue disease. The conditions of 19 (59%) patients were antinuclear-antibody-positive and 18 (56%) were rheumatoid-factor-positive. We found SS-A and/or SS-B autoantibodies in ten (31%) patients. There seems to be a high incidence of serologic abnormalities in patients with KCS, even when those patients with connective-tissue disease are excluded. Serologic testing seems to be a useful adjunct in the early diagnosis of primary Sjögren's syndrome. The presence of SS-A and SS-B autoantibodies correlated well with the clinical diagnosis of Sjögren's syndrome and seemed to identify the conditions of patients who may have a higher incidence of systemic complications with KCS.

Adult↗

The role of histones as nuclear autoantigens in drug-related lupus erythematosus.

Patients with drug-related lupus erythematosus produce antibodies to nuclear histones which can be detected by a three-step indirect immunofluorescence technique. Procainamide-related antinuclear antibodies were detected by this technique, but hydralazine-related antinuclear antibodies were not. Certain evidence suggests that antibodies induced by the two drugs are reactive with different subclasses of histones. Hydralazine was shown to interact with a soluble DNA-histone complex, and the resulting interaction rendered the histone moiety resistant to trypsin digestion. This mechanism may help to maintain DNA-histone complexes in a potentially immunogenic form and result in the production of autoantibodies.

Animals↗

A radial diffusion assay for plasma and serum deoxyribonuclease I.

A simple radial diffusion technique is described for assaying deoxyribonuclease I (DNase I) activity in whole human plasma and serum. Enzymatic activity was calculated from a standard curve constructed from the studies on the hydrolysis of calf thymus DNA by bovine pancreatic DNase of known concentrations. The assay was shown to be specific for nucleases which are active at neutral pH and require magnesium ions for activation. There was no significant difference in DNase I activity in plasma compared with that in serum from normal individuals (P greater than 0.05). The DNase I activity of 35 normal human sera was 26.1 +/- 9.2 ng/ml and ranged from 10.8-48.5 ng/ml. This technique may prove useful for the evaluation of DNase I activity in crude biological fluids and is not affected by the presence of enzymatic inhibitors and/or activators.

Adult↗

Serum deoxyribonuclease I and clinical activity in systemic lupus erythematosus.

Serum deoxyribonuclease I (DNase I) activity in systemic lupus erythematosus (SLE) patients was shown to be lower than that of healthy laboratory personnel, rheumatoid arthritis, and scleroderma patients (P less than 0.001). The decrease in DNase I activity in SLE sera was not due to the effect of various autoantibodies or to heat labile DNase I inhibitor. A relationship between serum DNase I activity and active SLE was demonstrated. Patients with active lupus nephritis had the lowest levels of enzymatic activity.

Adult↗

Serologic studies in a family with heterozygous C2 deficiency.

Twelve family members of a patient with systemic lupus erythematosus (SLE) and heterozygous deficiency of the second component of complement (C2) were studied. Histocompatibility (HLA) typing was determined for A, B, and DR and MB antigens. Serum samples were tested for a variety of antinuclear antibodies (ANA), lymphocytotoxic antibodies and rheumatoid factors, and C2 levels were determined by hemolytic titration. Inheritance of C2D, the gene coding for C2, was limited to the haplotype HLA-A25, B18, DR2. Low but significant titers of ANA, rheumatoid arthritis nuclear antigen (RANA) and/or rheumatoid factors were found in eight of the nine adult family members without association with HLA haplotype. The sister of the proband had persistently strongly positive LE cell preparations for more than a decade and had joint pains while taking sulfa drugs. The son of the proband had leukemia. All other family members were healthy. We conclude that the increased incidence of rheumatic disease in persons with C2D deficiency is multifactorial and requires environmental factors or other hereditary factors unrelated to the HLA-A25, B18, DR2 haplotype. The C2D gene is clearly not associated with positive ANA tests or immunoprecipitins to RANA.

Adult↗