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Biomedical subjects

J Karsh

Publications and source records attributed to J Karsh.

At least 19 recordsLinked to original sources
PubMed1992

CD7- T cells in rheumatoid arthritis.

OBJECTIVE: Rheumatoid arthritis (RA) is characterized by decreased expression of CD7 in the peripheral blood and in the synovium. The present study was designed to identify the basis for and functional consequences of this decreased expression. METHODS: Peripheral blood lymphocytes from normal controls and from patients with RA or systemic lupus erythematosus (SLE), and T cell lines derived from rheumatoid synovium, were evaluated using 3-color fluorescence-activated cell sorter analysis. RESULTS: Normal subjects and most SLE patients expressed homogeneous, bright CD7 on CD4+, CD45RA+ cells, whereas RA patients demonstrated a significantly increased proportion of CD7- cells. T cell lines derived from rheumatoid synovium demonstrated a striking deficiency of CD7 on CD4+, CD45RA- cells. CD4+, CD45RA+ cells from RA patients changed phenotype after in vitro activation to CD45RA negativity, with up-regulation of CD7. CD7-, CD4+, CD45RA- cells were assessed for their ability to induce pokeweed mitogen-driven IgM and IgM-rheumatoid factor synthesis, and they were found to be potent helper/inducer cells. An increased population of CD7-, CD4+ cells in peripheral blood was found to predict a low response to recall antigens. CONCLUSION: The low expression of CD7 in RA may explain some of the immune abnormalities which may contribute to the pathogenesis of this disease.

Adult↗
PubMed1992

Inhibition of alloreactivity in vitro by monoclonal antibodies directed against restricted isoforms of the leukocyte-common antigen (CD45).

The leukocyte common antigen (LCA) is a protein tyrosine phosphatase and is identified by the CD45 cluster of monoclonal antibodies. CD45 is expressed in high-density on cells of hematopoietic lineage and generally is immunoprecipitated as 4 bands (220, 205, 190, and 180 KDa). Genetic studies have shown that a single gene produces additional forms of the molecule by alternate splicing including CD45RA (220, 205), CD45RO (180), and CD45RB (220, 205, 190). We have prepared a CD45RB Mab termed "MT3" that binds to a sialic acid dependent epitope. Since the LCA is one of the major targets of antilymphocyte globulin, we assessed a panel of CD45 and CD45R Mab for their ability to inhibit alloreactivity in vitro. MT3 (CD45RB) inhibits the allogeneic MLR and inhibits CD4+ T cells from expressing interleukin 2 receptors, and prevents CD4+ CD45RA- T cells from entering the proliferative phase of the cell cycle. Mem 93 (CD45RA) inhibits the generation of cytotoxic T cells. These data suggest that the CD45RB and CD45RA isoforms of the LCA may be appropriate targets for in vivo immunotherapy.

Antibodies, Monoclonal↗
PubMed1992

Studies of the HLA class II alleles involved in human responses to ragweed allergens Ambrosia artemisiifolia V (Ra5S) and Ambrosia trifida V (Ra5G)

Previous studies have associated skin test sensitivity and specific IgE response to Ambrosia artemisiifolia V (Amb a V) with HLA-DR2, and to Ambrosia trifida V (Amb t V) with HLA-DRw52 haplotypes in atopic individuals. Using HLA class II typing by restriction fragment length polymorphism (RFLP) analysis with DRB, DQB and DQA DNA probes to define the HLA-D alleles, we have demonstrated the association of the DQw6 in 16 out of 16 (100%) Amb a V-responsive individuals, compared to 3 out of 18 (17%) ragweed-sensitive but Amb a V-nonresponsive individuals (p = 5.7 x 10(-6), RR greater than 75). We suggest that the DQw6 association with Amb a V sensitivity may be a reflection of an association with the DQA*0102 allele. This suggests an association of a particular HLA class II allele with an immune response to a well-characterized antigen (Amb a V). The HLA-DRw52 haplotypes in the Amb t V-sensitive individuals are not of one particular subtype. The HLA-DRw52 association with Amb t V sensitivity may reside in homologous DRB1 alleles linked on HLA-DRw52-bearing haplotypes.

Alleles↗
PubMed1992

Naproxen induced ulcerative esophagitis.

Only 4% of upper gastrointestinal bleeding in the elderly is due to ulcerative esophagitis, and only rarely has nonsteroidal antiinflammatory drug (NSAID) related esophageal bleeding been reported. We describe a case of NSAID induced ulcerative esophagitis in an 87-year-old woman with documented esophageal dysmotility.

Aged↗
PubMed1991

Methotrexate-induced asthma.

A patient with rheumatoid arthritis developed pulmonary symptoms and function test abnormalities consistent with asthma during methotrexate therapy. Assessments of airway responsiveness to methacholine during therapy revealed airway hyperreactivity that reverted to normal when the methotrexate was stopped. An extension of the methotrexate dosage interval from 7 to 10 days resulted in an abolition of the asthma, which remained in remission despite a return to a weekly cycle after a 3-month period of 10-day cycles.

Asthma↗
PubMed1989

Aspirin intolerance.

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Anti-Inflammatory Agents, Non-Steroidal↗
PubMed1989

In vitro IgM and IgM rheumatoid factor production in response to Staphylococcus aureus Cowan I and pokeweed mitogen: the contribution of CD5+ (Leu 1) B cells.

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.

Antigens, CD20↗
PubMed1989

Gold sodium thiomalate compared to low dose methotrexate in the treatment of rheumatoid arthritis--a randomized, double blind 26-week trial.

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.

Activities of Daily Living↗
PubMed1989

Cyclophosphamide treatment of interstitial pulmonary fibrosis in polymyositis/dermatomyositis.

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.

Adult↗
PubMed1988

Nonsecretory myeloma: a study on hypoimmunoglobulinemia.

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.

Agammaglobulinemia↗
PubMed1988

Decreased expression of CD7 occurs in rheumatoid arthritis.

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.

Adult↗
PubMed1987

In vitro IgM and IgM rheumatoid factor production in response to Staphylococcus aureus Cowan I: evidence for the role of Leu-2-positive T suppressor cells and radiosensitive T helper cells.

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.

Adult↗
PubMed1986

In vitro synthesis of IgM rheumatoid factor in response to Staphylococcus aureus, by lymphocytes from healthy adults.

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.

Adult↗