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Biomedical subjects

G C Sharp

Publications and source records attributed to G C Sharp.

At least 109 records · Page 6Linked to original sources
PubMed1979

Characterization of a distinct nuclear acidic protein antigen (MA) and clinical findings in systemic lupus erythematosus patients with MA antibodies.

Circulating antibodies against certain nuclear acidic protein antigens have been shown to have diagnostic and prognostic importance in connective tissue disease. We describe a new precipitin system found in the sera of patients with systemic lupus erythematosus. The antigen, called MA, was prepared from calf thymus nuclei, and was shown to be distinct from other nuclear acidic protein antigens by physicochemical and immunologic techniques. MA antibodies were detected in the serum of 12 of 66 lupus patients and in none of 554 sera from normal controls or patients with other rheumatic diseases. Lupus patients having MA antibodies had more severe disease than did lupus patients with Sm or native DNA antibodies, manifested by recalcitrant skin rashes and a significantly greater incidence of hypocomplementemia, serious renal disease, hypertension, hepatosplenomegaly, lymphadenopathy, and neurological disease (P values range from 0.025 to 0.005). The presence of circulating MA antigen was demonstrated in three lupus patients immediately before a flare of nephritis. These data suggest that MA is a nuclear acidic protein antigen that may identify a subset of lupus patients with very severe disease. The presence of the antigen in the circulation before clinical flares suggests a possible biologic role for the MA system in an immune complex nephritis.

Antibodies, Antinuclear↗
PubMed1978

Antibodies to nuclear antigens in patients with renal failure.

Nuclear material, presumably from damaged leukocytes, adheres to hemodialysis membranes. Previous studies have shown an increased prevalence of antibodies to nuclear antigens in chronic dialysis patients. Present studies verify the increased prevalence of antibodies to nuclear antigens in 52 of 243 chronic dialysis patients (21.4%). Because antibodies are present only intermittently, prevalence increases with repetitive blood sampling. In patients tested every 3 months over several years on chronic dialysis, the prevalence of antinuclear antibodies approaches 100%. The present studies also demonstrate, however, that the prevalence of antibodies is increased in patients with renal failure who have never undergone hemodialysis (10 of 86, 11.6%). Thus the tendency to form antibodies to nuclear antigens may be associated with renal failure rather than dialysis per se. Higher prevalences with increased time on dialysis and transplantation failure may accordingly reflect the greater duration of renal failure. The prevalence of antibodies to nuclear antigens was not significantly influenced by age, sex, type of kidney disease, major blood group, HLA tissue type, or coil reuse. Significantly lower hematocrits and white blood counts were noted when antibodies were present.

Adult↗
PubMed1977

Antinuclear antibody with distinct specificity for polymyositis.

In the course of studying antinuclear antibodies in the rheumatic diseases, a new precipitin reaction (provisionally referred to as PM-1) was observed between calf thymus nuclear extract and polymyositis sera. Objectives of this study were to further define the immunologic nature of this reaction and to determine its specificity for polymyositis. Immunodiffusion studies using calf thymus nuclear extract revealed the PM-1 precipitin line in 17 of 28 patients with polymyositis. This reaction was not produced by sera of 460 patients with other diseases. Enzyme and heat treatments of the nuclear extract showed that PM-1 was distinct from native DNA, ribonucleoprotein, and Sm antigens. Fractionation of PM-1-positive serum by 30% ammonium sulphate and Sephadex G-200 chromatography revealed that the factor producing the PM-1 precipitin reaction was in a serum fraction which showed only IgG by immunoelectrphoresis against anti-whole human serum. Because of the apparent strong specificity, the PM-1 system may represent a marker antibody for polymyositis.

Antibodies, Antinuclear↗
PubMed1976

Association of antibodies to ribonucleoprotein and Sm antigens with mixed connective-tissue disease, systematic lupus erythematosus and other rheumatic diseases.

Extractable nuclear antigen contains ribo-nuclease-sensitive (ribonucleoprotein) and ribonuclease-resistant (Sm) components. To determine the diagnostic usefulness of antibodies to these antigens, a multicenter study was undertaken in which serums were analyzed for these antibodies and the findings compared with clinical and other laboratory characteristics of the patients. Of 100 patients with hemagglutinating antibodies to ribonuclease-sensitive extractable nuclear antigen, and only the same antibodies by immunodiffusion, 74 per cent had typical features of mixed connective-tissue disease; 12 features of systemic lupus erythematosus, eight those of scleroderma and six an undifferentiated mild connective-tissue disease. Of 27 patients with hemagglutinating antibodies to ribonuclease-resistant extractable nuclear antigen (and Sm antibodies by immunodiffusion), 85 per cent had typical systemic lupus. Thus, antibodies to nuclear ribonucleoprotein and Sm are of diagnostic use; if the serum contains only ribonucleoprotein antibody in high titer, it is likely that the patient has mixed connective-tissue disease.

Adolescent↗
PubMed1976

Antibodies to nuclear antigens in patients undergoing long-term hemodialysis.

Free nuclei of damaged leukocytes adhere to hemodialysis membranes. To see if the incidence of antibodies to nuclear antigens is increased in patients receiving hemodialysis, serums from 77 patients undergoing long-term dialysis for one to 66 months were assayed for antibodies to extractable nuclear antigen and native deoxyribonucleic acid (DNA) by hemagglutination technics. Serums from 300 other hospital patients (who did not have diseases known to be associated with antibodies to nuclear antigens) were assayed concurrently. Of the 77 dialysis patients, serums from 19 (25 per cent) were positive for one or both antibodies. Serums from only three (1 per cent) of the 300 other patients had detectable antibodies. The incidence was significantly higher (p less than 0.001) in dialysis patients suggesting the possibility of sensitization to nuclear antigens during hemodialysis.

Adolescent↗
PubMed1976

Reproductive performance and fertility testing in strain 13 and Hartley guinea pigs.

A study to test the effects of certain experimental manipulation on the reproductive capacity of male guinea pigs required verifying the fertility of the male guinea pigs before and after manipulation. Methods of testing fertility were evaluated, and normal reproductive data from preexperimental and control groups were tabulated and analyzed. No data from the actual experiments were included. Virgin and proven fertile males were mated with 1 (1:1) or 2 (2:1) virgin or proven fertile females. Inbred (13/N Umm) and conventional (Mfi:CFDH-ML (DH) ) guinea pigs were used. Ninety-five percent of both groups of males were fertile. Eighty-four percent of both groups of females were fertile. Male guinea pigs previously proven fertile had the same subsequent fertility rate as virgin males. Over one-third of the conceptions did not take place during the first estrus cycle (16 da) during which the males and females were mated. Strain 13 and Hartley females had litters of approximately the same size (3.1 vs 3.0), but the neonatal mortality was statistically lower (P less than 0.001) in the Hartley stock (9.3%) than in the Strain 13 guinea pigs (28.4%).

Animals↗
PubMed1975

Extractable nuclear antigen effect on the DNA anti-DNA reaction and NZB/NZW mouse nephritis.

Extractable nuclear antigen (ENA) is composed of at least two components, one a ribonucleo-protein sensitive to ribonuclease or heat and the other a protein. Antibodies to ENA are associated with a relatively benign clinical course in patients with systemic lupus erythematosus (SLE) in which DNA anti DNA complexes are thought pathogenic. The effect of ENA and anti-ENA on DNA anti-DNA reactions in vitro was studied. ENA effectively inhibited an anti-DNA hemagglutination reaction but no effect was found on binding of radioactive DNA or on the anti-hemocyanin hemagglutination reaction. The inhibitory effect was not abolished by yeast ribonuclease (RNase), heating, or DNase. Anti-ENA HAD NO EFFECT ON ANTI-DNA hemagglutination. In vivo, ENA altered the NZB/NZW mouse nephritis thought to be a model for human SLE nephritis. These results suggest the possiblity of a role for ENA in alteration of diseases due to pathogenic DNA anti-DNA complexes.

Animals↗
PubMed1975

Differential susceptibility of strain 2 and strain 13 guinea pigs to induction of experimental autoimmune thyroiditis.

Twenty-seven of 30 Strain 2 guinea pigs immunized with 100 mug guinea pig thyroglobulin (GPTG) prepared either from Hartley (H) or Strain 13 (13) thyroids developed experimental autoimmune thyroiditis (EAT) whereas only 1 of 39 similarly immunized Strain 13 guinea pigs developed EAT. F1 hybrids behaved like the Strain 2 parent in that 16 of 20 developed EAT. The susceptible Strain 2 and F1 guinea pigs had higher hemagglutinating antibody titers to GPTG than the Strain 13 guinea pigs whereas all three strains had similar delayed skin reactivity to GPTG. The results suggest that susceptibility of guinea pigs to thyroiditis is genetically controlled and that production of antithyroglobulin antibody may be important in determining disease susceptibility.

Animals↗