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G C Sharp

Publications and source records attributed to G C Sharp.

At least 91 records · Page 5Linked to original sources
PubMed1984

Characterization of the autoimmune antigenic determinant for ribonucleoprotein (RNP) antibody.

Small nuclear ribonucleoprotein complexes are antigens in various autoimmune diseases. The serological pattern of high titers of circulating antibody to nuclear ribonucleoprotein (RNP) antigen is a diagnostic marker for mixed connective tissue disease (MCTD); whereas antibody to Sm is prevalent in systemic lupus erythematosus (SLE). Both calf thymus and rabbit thymus are commonly used, excellent sources for preparation of the corresponding antigens RNP and Sm in clinical and research laboratories (A. M. Boak et al., accompanying paper). Thus, biochemical and structural characterization of the minimal antigenic determinant in these preparations is important for its use in the laboratory, as well as significant for understanding MCTD, SLE, and other examples of autoimmunity. Purification and biochemical analyses of immunologically active RNP from many different preparations of calf thymus extract has revealed that the majority of antibody in monospecific MCTD patient sera recognizes an antigen composed of the 165 nucleotide RNA, U1 RNA, and five peptides. Calf thymus U1 RNA was found to be identical in sequence to that of man. A sequence of 55 nucleotides within the 165 nucleotide RNA was the minimal RNA fragment found in RNP particles that were still immunologically active. Two of the RNP peptides react with patient sera monospecific for RNP and thus, are presumably the antigenic peptides complexed with the 55 nucleotide RNA sequence.

Animals↗
PubMed1984

Clinical relevance of PM-1 antibody and physiochemical characterization of PM-1 antigen.

Using an improved immunodiffusion test with partially purified antigen, PM-1 antibody was identified in the serum of 18 patients. In 67% this system was associated with a polymyositis-scleroderma overlap, it occurred less frequently in polymyositis, dermatomyositis and scleroderma, and was not detected in other rheumatic diseases. The predominant clinical features of PM-1 positive patients were muscle weakness, sclerodactyly, Raynaud's phenomenon and pulmonary disease; widespread sclerodermatous features with infrequent. Characterization of the PM-1 antigen showed it to be a heat sensitive, trypsin sensitive acidic protein associated with the cell nucleus and possibly with nucleoli.

Antibodies, Antinuclear↗
PubMed1983

Adoptive transfer of experimental autoimmune thyroiditis (EAT) in guinea pigs: requirement for Ia-positive antigen-presenting cells for in vitro activation of effector T cells.

Lymph node T cells from guinea pigs sensitized in vivo with guinea pig thyroglobulin (GPTG) could transfer experimental autoimmune thyroiditis (EAT) to normal syngeneic recipients after in vitro culture with GPTG or GPTG-pulsed peritoneal exudate cells (PEC). Although EAT effector T cells have been shown previously to be Ia negative at the time of transfer, the addition of specific anti-Ia serum to the cultures inhibited effector cell activation. The inhibitory effect of anti-Ia on effector-T-cell activation was shown to be due to inhibition of the function of antigen-presenting PEC rather than to an effect on the sensitized T cell. Moreover, only Ia-positive PEC could present antigen in this system and Ia matching between the PEC and the T cell was required for effective T-cell activation. GPTG-pulsed Strain 2 (EAT susceptible) and Strain 13 (EAT resistant) PEC could both present antigen to T cells from 2 X 13 F1 guinea pigs although Strain 2 PEC were more effective, suggesting that defective antigen presentation by macrophages may at least partially explain the relative resistance to EAT of Strain 13 guinea pigs. These results indicate that interaction between Ia-positive PEC and sensitized T cells in vitro is necessary for the development of active effector T cells that can transfer EAT.

Animals↗
PubMed1983

Effect of guinea pig thyroglobulin in incomplete Freund's adjuvant on experimental autoimmune thyroiditis induced by in vitro-activated lymph node cells.

Guinea pigs injected with guinea pig thyroglobulin (GPTG) in incomplete Freund's adjuvant (IFA) have been shown to be unresponsive to challenge with GPTG in complete Freund's adjuvant (CFA). However, effector cells which transfer experimental autoimmune thyroiditis (EAT) can be demonstrated in cultured lymph node cells (LNC) of unresponsive animals, indicating that GPTG in IFA does not suppress the initial sensitization of EAT effector cells. LNC from unresponsive animals were unable to suppress the in vitro activation of effector LNC or to suppress EAT when cotransferred with effector cells. When GPTG in IFA was given to animals which were used as recipients of effector cells, the production of EAT was markedly suppressed. These results suggest that GPTG in IFA can suppress EAT either by preventing effector cells from interacting with the thyroid or by interfering with the function of a cell in the normal recipient which may interact with effector cells to result in the lesions of EAT.

Animals↗
PubMed1983

AI/RHEUM. A consultant system for rheumatology.

A knowledge-based computer consultant system in the medical specialty area of rheumatology is described. The system, called AI/RHEUM, uses artificial intelligence techniques to provide nonrheumatologist physicians with diagnostic assistance in this specialty area. AI/RHEUM contains in a structured knowledge base formal criteria for 26 rheumatologic diseases. The system has been retrospectively tested against 384 clinical cases, with an overall correct diagnostic performance of 94%.

Computers↗
PubMed1983

Cardiovascular manifestations of mixed connective tissue disease in adults.

To assess the nature and distribution of cardiovascular abnormalities associated with mixed connective tissue disease, we studied 38 patients with overlapping clinical manifestations of systemic lupus erythematosus, progressive systemic sclerosis and polymyositis, and circulating antibodies to nuclear ribonucleoprotein. The protocol included taking a medical history and a physical echocardiogram, and pulmonary function tests. Cardiac catheterization was performed on 17 patients. Postmortem examination was performed on four of the five patients who died during follow-up. Acute pericarditis and/or pericardial effusion was detected in 11 patients (29%) and mitral valve prolapse was identified in 10 patients (26%). Marked intimal hyperplasia of coronary arteries was observed in all four hearts that were autopsied and perivascular and myocardial leukocytic aggregates were present in two hearts. Pulmonary vascular resistance was elevated in 11 of the 17 patients who underwent cardiac catheterization. In summary, cardiovascular abnormalities associated with mixed connective tissue disease include acute pericarditis and/or effusion, mitral valve prolapse, intimal hyperplasia of coronary arteries, perivascular and myocardial leukocytic infiltrates, and pulmonary hypertension.

Adolescent↗
PubMed1983

Liver disease in mixed connective tissue disease.

Previous descriptions of mixed connective tissue disease (MCTD) have not included evidence of hepatic involvement. A patient who had MCTD also had severe chronic active hepatitis. Retrospective review of all of our cases of MCTD confirms that liver disease is an uncommon occurrence in MCTD.

Adult↗
PubMed1981

Adoptive transfer of experimental autoimmune thyroiditis (EAT) with in vitro activated lymph node cells from thyroglobulin-sensitized guinea pigs: characterization of the cell that transfers EAT.

Relatively low numbers of lymph node cells (LNC) from Strain 2 or Strain 13 guinea pigs sensitized with guinea pig thyroglobulin (GPTG) could transfer experimental autoimmune thyroiditis (EAT) to normal syngeneic recipients after in vitro culture with GPTG. The EAT induced in recipients of cultured LNC was similar in incidence and severity to EAT induced by active immunization with GPTG in complete Freund's adjuvant. The cells that were effective in transferring EAT were shown to be immunoglobulin-negative, nylon wool nonadherent, and Ia-negative. The effector cells were sensitive to irradiation after in vitro activation, indicating that cell proliferation in the recipient is required for development of EAT. Recipient animals often developed moderate to severe lesions of EAT yet none had detectable delayed hypersensitivity to GPTG and the majority also had no detectable anti-GPTG antibody.

Animals↗
PubMed1980

Diagnostic potential of in vivo capillary microscopy in scleroderma and related disorders.

The prevalence of scleroderma-type capillary abnormalities, as observed by in vivo microscopy, was determined in 173 patients from three rheumatic disease centers. The patients had a variety of connective tissue diseases: scleroderma (systemic sclerosis) 50; systemic lupus erythematosus 60; mixed connective disease 26; Raynaud's disease 11; other rheumatic disorders 26. Enlarged and deformed capillary loops surrounded by relatively avascular areas, most prominently in the nail-folds, were found in 82% of patients with scleroderma and in 54% with mixed connective tissue disease. The rarity of these abnormalities in systemic lupus erythematosus (2%) despite the presence of Raynaud's phenomenon suggests that they are not an expression of the Raynaud's phenomenon frequently associated with scleroderma and mixed connective tissue disease. The single patient with Raynaud's disease and sclerodermatype capillary changes subsequently developed scleroderma.

Adolescent↗
PubMed1980

Current concepts in the classification of connective tissue diseases. Overlap syndromes and mixed connective tissue disease (MCTD).

New principles are discussed for the classification of the diffuse collagen diseases, particularly the mixed connective tissue disease (MCTD), with clinical and historical explanation. Emphasis in classification has shifted from a concern with tissue pathology to serologic anomalies, which may involve eleven different antigens, many from human cell nuclei. New serologic tests, such as the ribonucleoprotein (RNP) antibody test, may be superior to the well-known fluorescent antinuclear antibody (ANA) studies for diagnosis and follow-up of diffuse collagen diseases. Functional clinical studies, such as esophageal motility, gas exchange in the lung, and major joint mobility, which may appear early in MCTD, are more important to diagnosis than anatomic studies of late-developing lesions.

Connective Tissue Diseases↗
PubMed1980

Purification and biochemical characterization of nuclear ribonucleoprotein antigen using purified antibody from serum of a patient with mixed connective tissue disease.

We have achieved a high degree of purification of nuclear ribonucleoprotein antigen from calf thymus nuclear extract through antibody affinity chromatography. Antibody to nuclear ribonucleoprotein was purified from the serum of a patient with mixed connective tissue disease and Sepharose 4B was covalently coupled with the purified human antibody. The sodium thiocyanate eluate from the affinity column contained active ribonucleoprotein antigen and the specific activity of the antigen in this eluate was 488 times higher than the original nuclear extract. The protein component of the eluate consisted of six polypeptides determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Two of them were shown to be antigenic by a hemagglutination inhibition test. The molecular weights of these two peptides were approximately 13,000 and those of the other four were 13,000, 13,000, 30,000, and 65,000. The ribonucleic acid component of the eluate was shown by urea-polyacrylamide gel electrophoresis to contain five polynucleotides. Two of the five, estimated to contain 40 and 60 nucleosides, had antigenic activity. The other three polynucleotides which had more than 77 nucleosides had no antigenic activity. No modified nucleosides were found in these ribonucleic acid molecules. Even in this highly purified ribonucleoprotein antigen, Sm antigen was detected by immunodiffusion. This evidence indicated that there are some molecular associations between ribonucleoprotein and Sm antigens as has previously been suggested.

Amino Acids↗
PubMed1979

Identification of a clinical subset of systemic lupus erythematosus by antibodies to the SM antigen.

The clinical and renal histologic attributes of 135 systemic lupus erythematosus (SLE) patients with DNA and/or Sm antibodies were compared to determine if the presence of the Sm antibodies served as a marker for a specific subset of SLE. Although Raynaud's phenomenon was more frequent in patients with Sm antibodies (P less than 0.005), serious central nervous system disease was over three times as common in patients with DNA antibodies (P less than 0.005). Only one of 23 patients with Sm antibodies had diffuse proliferative glomerulonephritis on renal biopsy, whereas 6 of 14 patients with only DNA antibodies had this histologic finding (P = 0.01). The Sm antibody system may therefore identify a subset of SLE patients with milder central nervous system and renal disease.

Antibodies, Antinuclear↗