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Biomedical subjects

G A McCarty

Publications and source records attributed to G A McCarty.

34 records · Page 2Linked to original sources

Speckled pattern antinuclear antibodies resembling anticentromere antibodies.

Two distinct nuclear antigens, designated NSpI and NSpII, have been characterized and differentiated from the centromeric antigen that reacts with sera from patients with the CREST syndrome. Both NSpI and NSpII produce a speckled pattern of indirect immunofluorescence on HEp-2 cells that resembles the pattern seen with anticentromere antibodies (ACA). They are differentiated from the ACA staining pattern by the absence of metaphase chromatin staining by NSpI antisera and by the absence of a discrete speckled pattern of staining by NSpII. Further, both NSpI and NSpII stain predominantly the peritubular nuclei of mouse kidney cryostat sections. NSpII is sensitive to trypsin, proteinase K, and HCI extraction, suggesting that it is a relatively soluble nuclear protein. NSpI was also sensitive to protease treatment but was not extracted with 0.1N HCl, suggesting that it is a tightly bound nuclear protein.

Antibodies↗

NuMA protein is a human autoantigen.

Routine examination of sera from patients with suspected or confirmed connective tissue disease has revealed the presence of autoantibodies directed against an unusual nuclear antigen. As characterized by immunofluorescence studies, the antigen is found exclusively in the nuclei of interphase cells, but appears to be part of the spindle pole in mitotic cells. Similar distributions in interphase and mitotic cells have been reported for the recently discovered nuclear mitotic apparatus (NuMA) protein. Using immunoblot analysis we have demonstrated that the autoantibodies that decorate the mitotic spindle poles are specific for the NuMA protein. Therefore, we conclude that the NuMA protein is a human autoantigen.

Antibodies↗

Autoantibodies to nuclear, cytoplasmic, and cytoskeletal antigens in renal allograft rejection.

Autoantibodies (AA) detected by indirect immunofluorescence on HEp-2 cells and lymphocyte panel reactive antibodies (PRA) were measured pretransplant and within 2 weeks after transplant nephrectomy in a group of 21 consecutive renal allograft recipients with irreversible graft rejection. No patient had clinical evidence or history of autoimmune disease. Although 43% of patients had AA and 29% had a positive PRA pretransplant, 90% had AA and 100% had a positive PRA post-transplant nephrectomy (P less than 0.0032, 0.00001, respectively). Analysis of AA detected following graft failure revealed that all were of IgG class, and more than half the patients had multiple patterns including speckled nuclear, cytoplasmic, perinuclear, mitotic spindle apparatus, and smooth muscle staining. Of 11 patients retested up to one year later, all showed a persistence of previously detected AA in both pattern and titer, although none of the patients had any other signs or symptoms of autoimmune disease. A control group of 21 transplant recipients with functioning grafts was similarly tested revealing that 35% had AA and 29% had positive PRA pretransplant, but only 14% had AA and 14% positive PRA posttransplant. The presence of post-transplant AA or PRA was not associated with antecedent delayed graft function (ATN), rejection episodes, treatment with antithymocyte globulin, the interval posttransplantation, or subsequent graft outcome. However, pretransplant AA and PRA in both groups were associated with prior graft loss, but not with other variables examined. These findings indicate that serologically detectable sensitization to lymphocyte (HLA) antigens and the presence of persistent, multiple autoantibodies to nuclear, cytoplasmic, and cytoskeletal antigens is a frequent occurrence following graft loss. Furthermore, the development of AA following graft rejection appears to be unrelated to the prior presence or subsequent development of clinical autoimmune disease.

Adolescent↗

Antibody to the mitotic spindle apparatus: immunologic characteristics and cytologic studies.

A naturally occurring autoantibody directed at the mitotic spindle polar apparatus (MSA) was detected in sera from 18 patients with defined or evolving connective tissue diseases by routine indirect immunofluorescence on a tissue culture cell. This IgG antibody stained the mitotic spindle poles of dividing tissue culture and tissue section substrates, with staining most prominent on substrates of human origin. With some sera, and cell lines, interphase cells showed isolated nuclear staining. Cytoplasmic staining was not apparent in any sera on any substrate. This specificity was shown to be distinct from tubulin by double fluorescence labeling studies. Patient sera exhibiting only this specificity did not precipitate antigens in rabbit or calf thymus nuclear extracts. However, several patients with systemic lupus erythematosus exhibited anti-MSA in combination with other autoantibodies. This autoantibody may be a useful probe for spindle pole-related structures.

Arthritis, Rheumatoid↗

Anticentromere antibody. Clinical Correlations and association with favorable prognosis in patients with scleroderma variants.

The presence of antibody to the chromosomal centromere appears to be associated with a subset of patients with the limited CREST form of scleroderma. To further define the prognostic value of this autoantibody, 27 patients, who were identified as having anticentromere antibody by screening antinuclear antibody tests using HEp-2 cell substrates, were followed clinically and serologically for 2 years. The presence of anticentromere antibody is common in the limited CREST forms of systemic sclerosis, and it is often the only autoantibody specificity present in the sera of patients with the CREST variant. When compared with other patients who exhibit speckled or nucleolar antinuclear antibody patterns, those with anticentromere antibody had significantly less major organ system involvement.

Adult↗

Clinical features of patients with antibodies directed against proliferating cell nuclear antigen.

The clinical and serologic features of 7 patients whose sera contained antibodies directed against proliferating cell nuclear antigen (anti-PCNA) were studied. Five of the patients had systemic lupus erythematosus (SLE), 1 had idiopathic diffuse proliferative glomerulonephritis, and 1 had seronegative arthritis. In a study of various rheumatic diseases, anti-PCNA was found in 2% of SLE sera but was not found in the sera of 100 rheumatoid arthritis patients, 20 mixed connective tissue disease patients, or 50 diffuse scleroderma patients. Patients with anti-PCNA had no history of hemolytic anemia, leukopenia, thrombocytopenia, or pleuro-pericarditis. Evidence that the production of anti-PCNA antibodies is sensitive to corticosteroid therapy is also presented.

Adult↗

Lymphocytic lymphoma and systemic lupus erythematosus: their coexistence with antibody to the Sm antigen.

The serologic and clinical features of a 32-year-old women with coexistent systemic lupus erythematosus and lymphoma were studied. A cervical node biopsy specimen demonstrated nodular, poorly differentiated lymphocytic lymphoma; subsequent development of polyarthralgias prompted evaluation for connective-tissue disease, and a high titer of antinuclear antibody was found. Immunochemical studies proved that this antibody was directed to the Sm antigen, a serologic finding highly specific for systemic lupus erythematosus. This antibody has been maintained throughout the course of the patient's disease, characterized by persistent lymphadenopathy, pleuropericarditis, arthritis, hypocomplementemia, hyperglobulinemia, and a slight elevation of titers of anti-DNA antibody. The course of the lymphoproliferative disorder has been consistent with that of an indolent non-Hodgkin's lymphoma. In sera from other patients with lymphoproliferative disorders, anti-Sm antibody was not found. These findings emphasize the importance of establishing the antigenic specificity of antinuclear antibodies detected in the sera of patients with neoplasia.

Adult↗

Mechanisms of autoantibody production in autoimmune MRL mice.

The quantitative expression of anti-DNA and anti-Sm antibodies has been investigated in autoimmune MRL-lpr/lpr and MRL-+/+ mice. Anti-Sm antibodies were detected in sera from 21/23 lpr/lpr and 10/16 +/+ mice, with individual animals showing striking variation in the time-course and magnitude of this autoantibody response. The peak antibody levels of the responding animals of each substrain did not differ significantly. For anti-DNA antibody, a different pattern of responsiveness was observed. Individual animals of each substrain produced very similar responses in terms of the magnitude and time-course of serum anti-DNA antibody. The differences in the peak levels of the two substrains were highly significant, with lpr/lpr mice demonstrating a much greater anti-DNA antibody response than +/+ mice. In lpr/lpr mice tested for both autoantibody systems, serum anti-DNA and anti-Sm antibodies showed distinct time-courses. These studies indicate that anti-DNA and anti-Sm antibodies are expressed independently in MRL mice, with the expression of anti-DNA, but not anti-Sm antibody markedly influenced by the presence of the 1pr gene. A fundamental difference in the mechanisms involved in the generation of anti-DNA and anti-Sm antibodies is suggested by the quantitative pattern of the two responses.

Animals↗

Deficiency of the fifth component of complement in human subjects. Clinical, genetic and immunologic studies in a large kindred.

The discovery of a large kindred with a heritable deficiency of the fifth component of complement (C5) has permitted the accumulation of new clinical, genetic and immunologic data concerning the role of C5 in human subjects. The proband, who has had nine episodes of disseminated gonococcal infection, has a hemolytic C5 level of approximately 0.5 per cent of normal. No C5 protein was detectable, but low levels of functional C5 activity could be found using a sensitive bactericidal assay. The proband's twin as well as another sister also had extremely low levels of hemolytic C5(approximately 0.5 per cent normal), but both these subjects have been healthy. Hemolytic complement and bacteriolytic activity could be restored by the addition of purified C5. No chemotactic activity for polymorphonuclear leukocytes could be generated in the C5-deficient serums upon activation of either the classic or alternative pathways, again demonstrating the importance of C5 in human subjects for the production of chemotactic factors. The chemotactic responsiveness of the patients' polymorphonuclear leukocytes and monocytes to preformed chemotactic factors was not depressed. Twenty-two of 32 other family members from three generations had depressed whole hemolytic complement levels. In 19 of 30 family members, levels of hemolytic C5 ranged from 13 to 64 per cent of normal. No linkage for C5 deficiency and the A or B loci of the major histocompatibility complex could be found. These data suggest an autosomal codominant mode of inheritance of C5 deficiency. Deficiency of C5 is compatible with good health, but it can be associated with repeated disseminated gonococcal infection.

Adult↗

Articulatory effects of monaural and binaural masking in normal speaking adults wearing palatal appliances.

Ten normal speaking adults (five male, five female) performed three speaking tasks during conditions of monaural and binaural masking with and without complete palatal appliances. Significant effects on the subjects' articulation were found for the factors of masking type, palatal appliance and speaking task. No significant effects were found for monaural right- versus monaural left-ear masking or sex of the speakers. The findings are similar to previous results using binaural masking and indicate that the disruptive effect of monaural masking on the articulation of adult subjects is approximately midway between the effects of no masking and binaural masking. It is suggested that the lack of a significant effect for right-ear versus left-ear monaural masking may be due to the high degree of automatization which subjects possessed for the stimuli used in the speaking tasks.

Adult↗

Intraoral infrared color photography of radiotherapy patients.

A clinical screening study was performed in which head-and-neck radiotherapy patients were photographed intraorally using infrared "false color" film and Ektachrome color film. These photographs were compared to determine if differences existed in appearance between the intraoral tissues within the field of radiation and those intraoral tissues not in the field of radiation. No differences could be detected with either the "false color" film or with Ektachrome color film. Further investigations in the use of infrared color photography as applied to the radiotherapy patient could be undertaken by using a light source that transmits infrared rays only and a lens filter that passes only infrared rays. This method would produce a film that shows only the reflected infrared rays. Both color and black-and-white film should be used in this study.

Color↗

Scleroderma: DR antigens, autoantibodies and clinical manifestations.

The relationship between anticentromere antibodies (ACA), antitopoisomerase I or Scleroderma 70 (Scl-70) antibodies, HLA-DR antigens, and clinical manifestations of scleroderma were examined in 51 patients defined by ARA criteria. No association between a given HLA-DR antigen and either ACA or anti-Scl-70 was found. Statistically significant associations were noted for patients with ACA who had a lower frequency of arthritis and longer disease duration; anti-Scl-70 patients were more likely to be males with a higher frequency of pulmonary, cardiac and sicca symptoms.

Adult↗

Independent expression of autoantibodies in systemic lupus erythematosus.

Antibodies to components of the cell nucleus have been viewed as specific serological markers of systemic lupus erythematosus (SLE). To determine whether these autoantibodies exhibit common regulation of their expression, antibody levels have been quantitatively assessed in serial samples from patients producing at least 2 different antibody specificities. In a comparison of the peak antibody levels as a measure of immune responsiveness, the magnitude of the antiDNA response varied independently of either the antiSm or the antiRNP responses. Serial analysis with selected patients demonstrated that antiDNA levels fluctuated according to a pattern related to disease activity. In the same patients, however, antiSm and antiRNP antibodies showed little variation in level, with no consistent relationship to disease activity. Furthermore, following therapy, antiDNA levels fell while neither antiSm nor antiRNP levels showed significant alteration. These results suggest that in SLE, autoantibodies may arise from distinct immunoregulatory disturbances, each characterized by a unique relationship to disease activity and response to therapy.

Antibodies, Antinuclear↗

Characterization and comparison of commercially available antinuclear antibody kits using single pattern index sera.

The wide variety of commercial kits used to test antinuclear antibodies (ANA) by indirect immunofluorescence (IIF) makes comparison of data from different laboratories difficult. Data comparing the sensitivity and feasibility of the various kits are not available. Eight different methods using tissue section and monolayer substrates for evaluating serum ANA by IIF were compared using single pattern ANA-positive sera. A rationale for selection among these kits and guidelines for interlaboratory comparison is presented.

Amnion↗