Aspirin intolerance.
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Biomedical subjects
Publications and source records attributed to J Karsh.
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The relation between the percentage of circulating CD5+ CD20+ B cells and the ability to synthesize IgM and IgM rheumatoid factor (RF) in vitro in response to pokeweed mitogen (PWM) and Staphylococcus aureus Cowan I (SAC) was assessed in 21 healthy controls. CD5+ CD20+ cells ranged from 7.3 to 19.9% of total CD20+ B cells. By Spearman's rank correlation, there was an inverse relation between the percentage of CD5+ CD20+ B cells and IgM production in response to PWM (rs = -0.452, p less than 0.05) and a direct correlation with RF production in response to SAC (rs = 0.450, P less than 0.05). The percentage of CD5+ CD20+ B cells was not related to any serologic HLA-A, B, C or D antigen. Healthy individuals may be predisposed to producing IgM or autoantibodies based on the percentage of circulating CD5+ Cd20+ B cells.
Thirty-five patients with definite or classic rheumatoid arthritis (RA) entered a prospective, double blind, randomized study of 26 weeks duration. All patients had active RA that was unresponsive to greater than or equal to 2 nonsteroidal antiinflammatory medications and/or antimalarials. Eighteen patients were randomized to receive methotrexate (MTX) 12.5 mg weekly (oral and noncycled) + placebo, and 17 patients to gold sodium thiomalate (GSTM) 50 mg IM weekly + placebo (schedule I) after initial test dose of 10 and 25 mg. Dose reductions from Schedule I to Schedule II (i.e. MTX 5.0 mg and GSTM 25 mg) were permitted at Weeks 6 and 12. The GSTM group showed statistically significant improvement at Week 26 compared with baseline status in all of the clinical efficacy variables and the MTX group in 7. There were no statistically significant differences in these outcome variables between the 2 groups at Week 26. However, this small sample size may not have detected a clinically significant difference between treatment groups (alpha = 0.05, beta = 0.20). Two of the 18 patients treated with MTX and 6 of the 17 patients treated with gold withdrew because of drug toxicity, but this difference was not statistically significant. In conclusion, GSTM and MTX are similarly efficacious in the short term treatment of RA.
Interstitial pulmonary fibrosis is a serious complication of inflammatory muscle disease associated with significant morbidity and mortality. We describe 3 consecutive cases complicating dermatomyositis (1 case, anti-Jo-1 antibody negative) and polymyositis (2 cases, anti-Jo-1 antibody positive) in which cyclophosphamide was added to prednisone therapy with favorable outcomes.
In evaluating hypoimmunoglobulinemia in a patient with nonsecretory myeloma, studies of in vitro immunoglobulin synthesis were performed during a 3-year period. Impaired polyclonal response to mitogen stimulation associated with excessive suppressor activity was demonstrable at diagnosis. Despite successful chemotherapy, serum immunoglobulin levels remained depressed with a persistent impairment in polyclonal immunoglobulin synthesis but without evidence for excessive suppression. In nonsecretory myeloma, as in secretory myeloma, a defective B-cell response to differentiation signals may be a contributory mechanism in the hypoimmunoglobulinemia seen in this disease.
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To evaluate the possibility of antigenic modulation in vivo, we studied the expression of the CD7 antigen on the surface of peripheral blood and intrasynovial lymphocytes from patients with rheumatoid arthritis (RA). This disease is noted for features predicting changes in CD7: (1) increased expression related to activation during an immune response through possible contact with 'disease associated antigens' and (2) decreased expression associated with lymphocytes moving through tissue. We found a highly significant decrease of CD7 on RA T cells in vivo (P less than 10(-4] that was not related to disease activity, drug ingestion, or abnormalities in the ability of RA T cells to express or modulate the antigen in vitro. Similar decreased expression was observed on many intrasynovial T cells that were nevertheless activated as measured by expression of activation markers such as Act I (a late lymphocyte activation antigen) and Act II (the transferrin receptor). Decreased expression of CD7 occurs naturally in vivo in RA; this observation may have future significance in better understanding the immunopathogenesis of this disease.
Staphylococcus aureus Cowan I (SAC) is a potent stimulus of B cell proliferation and differentiation, the latter being T cell-dependent. It has been suggested that immunoglobulin and IgM rheumatoid factor (RF) production in response to SAC involves radiosensitive T helper cells. We studied normal peripheral blood mononuclear cell (PBMC) cultures to assess the roles of radiosensitive T cells and Leu-2 positive suppressor cells in the cellular control of SAC-stimulated IgM and IgM RF responses. Depletion of Leu-2 positive T cells from reconstituted autologous PBMC cultures resulted in an increase in SAC-stimulated IgM production in the majority of individuals, implying the involvement of Leu-2 positive suppressor T cells in this system. Suppression by Leu-2 positive cells is less evident in the SAC-induced IgM RF response, suggesting qualitative differences between IgM and IgM RF SAC-stimulated responses in PBMC cultures from the same normal individuals. Irradiation (1000 rads) of the T cell-enriched subpopulation, either with or without Leu-2 positive cell depletion, resulted in statistically significant decreases in IgM and IgM RF production in response to SAC in reconstituted autologous cultures, providing further evidence of a Leu-2 negative radiosensitive sheep-cell rosetting cell active in in vitro SAC responses. In contrast, PWM-stimulated PBMC cultures showed almost exclusively increases in total IgM and IgM RF production when T cells were irradiated (1000 rads) before culture, consistent with the radiosensitive T suppressor cell involved in the in vitro immunoglobulin responses to PWM. The same five out of nine individuals produced IgM RF, under different culture conditions, in response to PWM and SAC, suggesting that the ability of an individual to produce IgM RF lies intrinsically within the B cell.
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A patient with longstanding Mollaret's meningitis had an increased number of circulating natural killer cells during an acute attack, as evidenced by 73% large granular lymphocytes and 80% Leu-11a-positive peripheral mononuclear cells. Numbers of large granular lymphocytes and Leu-11a-positive cells returned to normal by three months after the attack. Similarity of the morphological features of the Mollaret's cell to those of large granular lymphocytes is noted.
Peripheral blood mononuclear cells from 20 healthy adults were tested in vitro for the production of IgM rheumatoid factor (RF) in response to Staphylococcus aureus Cowan I (SAC) or pokeweed mitogen. Fifteen of the 20 normal subjects produced greater than or equal to 4 ng/ml IgM-RF (mean +/- SD 46 +/- 55 ng/ml) in response to SAC, compared with only 2 of 20 who produced greater than or equal to 4 ng/ml IgM-RF (mean +/- SD 2 +/- 4 ng/ml) in response to pokeweed mitogen (P = 0.0001). Separation and reconstitution of autologous T and B cell-enriched fractions, with and without prior T cell irradiation, provided evidence for a radiosensitive T helper/inducer cell involved in the IgM-RF response to SAC in 70% of the normal subjects studied. SAC appears to be a potent stimulus of IgM-RF production, with a cellular mechanism distinct from that of other in vitro systems.
Polyarteritis nodosa was diagnosed in a patient one year after an episode of severe serous otitis media and 2 1/2 years after initiation of a 23 month course of hyposensitization therapy for nonseasonal rhinitis. Relationships among immunotherapy, otitis media and polyarteritis nodosa merit emphasis because their recognition may lead to early diagnosis.
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Fibronectin (Fn) was detected in 12/14 2.5% polyethylene glycol precipitates of rheumatoid serum positive for rheumatoid factor (RF). This association led to an investigation of the capacity of Fn to interact with IgM RF and heat aggregated human IgG. Our data suggest that Fn can interact directly with both of these substances at a site in the Fc fragment of the immunoglobulin molecule. The exact cite of the interaction is still to be defined but evidence indicates that it is probably distinct from sites binding staphylococcal protein A and complement.
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Immunogenicity of 14 valent pneumococcal vaccine was evaluated in a placebo controlled, double blind, randomized study involving 77 patients with systemic lupus erythematosus (SLE). Antibodies to 12 type specific capsular antigens were measured prior to and one and 6 months post injection. In 17 patients treated with prednisone plus cyclophosphamide and/or azathioprine, mean body concentrations (ng antibody nitrogen/ml serum) increased from 528 to 1328 and 852, respectively, in vaccinated patients compared to 307, 308 and 344 following placebo. In 60 patients not receiving immunosuppressives, mean antibody concentrations were 355, 1361 and 920 post vaccine and 401, 473 and 377 post placebo. Our study demonstrates that antibody responses to pneumococcal vaccine in SLE patients is unaffected by these immunosuppressive agents.
Joint mobility was assessed in 80 consecutive adult noninsulin-dependent diabetic (NIDD) patients and 47 nondiabetic controls matched for age and sex. Impairment of mobility was observed in 36 NIDD patients but only 7 controls (p less than 0.01). There was no significant differences between diabetic patients with and without impaired mobility with regards to age, duration of diabetes, mean daily insulin dose, or overall diabetic control as assessed by the measurement of glycosylated haemoglobin (HbA1C). However, NIDD patients with impaired joint mobility had a significantly increased frequency of microvascular disease, as shown by retinopathy and/or nephropathy (42% versus 22%, p less than 0.05), were more often on insulin treatment (86% versus 63%, p less than 0.05) and more frequently had additional rheumatic disorders such as Dupuytren's contracture and osteoarthritis (36% versus 18%, p less than 0.05). In addition tight waxy skin over the phalanges was commonly associated with impaired mobility (58% versus 22%, p less than 0.01). Limitation of joint mobility was most prominent in the hands but caused no functional impairment. This finding may be an additional marker of microvascular disease in the adult diabetic patient.