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Biomedical subjects

E C Keystone

Publications and source records attributed to E C Keystone.

At least 37 records · Page 2Linked to original sources

Origin of defective T lymphocyte-suppressor activating factor interaction in patients with rheumatoid arthritis.

We previously examined the generation of T cell released suppressor activity (TRSA) from peripheral blood T cells from patients with rheumatoid arthritis (RA) in response to a soluble suppressor activating factor (SAF) produced by a 6-thioguanine resistant mutant of the human T cell line CEM. We reported (Lau et al., 1985 Clin. exp. Immunol. 61, 481) that T cells from a substantial proportion of RA patients exhibited impaired TRSA release. To delineate further the TRSA abnormality observed in patients with active RA, we evaluated the kinetics of SAF activation, precursor frequency of SAF reactive cells and quantity of activated SAF released on a per cell basis. The results showed that a lower precursor frequency of SAF reactive cells accounted for defective TRSA release in a majority of RA patients, while TRSA release on a per cell basis was normal. The defective TRSA response to SAF could not be explained by abnormal dose kinetics of SAF, time kinetics of TRSA release or prior in vivo lymphocyte activation of the RA T cells.

Adult

Lymphocytotoxins in vasculitis. Correlation with clinical manifestations and laboratory variables.

Twenty-eight of 53 patients with various types of vasculitis were found to have cold reacting lymphocytotoxins (LCT). LCT were cytotoxic to both peripheral blood B and T cells as well as to OKT4 and OKT8 subpopulations. The interaction with the B cells was more pronounced than with the T cells as shown by reactivity with the former at higher serum dilutions than with the latter. Similar results were obtained with eluates from the unseparated lymphocytes and from B or from T cells. Partial purification of LCT demonstrated that they belong to the IgM class. LCT correlated with the level of circulating immune complexes as determined by the fluid phase C1q binding assay, but they did not correlate with the level of immunoglobulins, complement or antinuclear factors. The presence of LCT correlated significantly with the activity but not with the disease duration or the number of involved organs. Correlation of LCT with the activity of vasculitis implies that these cytotoxins may have a pathogenetic role and perhaps may serve as a marker for disease activity.

Antigen-Antibody Complex

In vivo activation of lymphocytes in rheumatoid arthritis.

Spontaneous in vivo proliferation of peripheral blood mononuclear cells (PBM) and T and B lymphocytes from 28 patients with rheumatoid arthritis (RA), 20 healthy individuals and 13 patients with psoriatic arthritis was evaluated. PBM, T (E+) and non-T (E-) cells from patients with active RA proliferated significantly more than the same populations from healthy individuals and patients with inactive RA. In contrast, only E+ cells from PSA patients showed a trend to increased proliferation relative to healthy individuals. AET treated sheep red blood cells (SRBC) inhibited 3HTdR incorporation of highly profilerating PBM of active RA patients. The data suggest in vivo activation of both B and T cells in patients with clinically active RA.

Adult

Enhanced interleukin 1 generation by monocytes in vitro is temporally linked to an early event in the onset or exacerbation of rheumatoid arthritis.

Twenty-one patients with rheumatoid arthritis (RA) and 12 age and sex matched healthy controls were examined for the ability of their monocytes (adherent cells, AC) to spontaneously secrete interleukin 1 (IL-1) and for their peripheral blood mononuclear cells (PBMC) to secrete interleukin 2 (IL-2) induced by Staphylococcal Protein A (SPA). All RA patients had PBMC which secreted normal amounts of mitogen induced IL-2 regardless of disease activity or disease history. However, AC from RA patients who had a recent (less than 6 months) onset of their disease, or exacerbation of existing RA, had enhanced spontaneous IL-1 secretion. AC from patients with equally active RA but with historically stable disease generated normal amounts of IL-1. Enhanced in vitro IL-1 generation by circulating monocytes is temporally linked to an early event in the onset of exacerbation of RA.

Acute Disease

Interleukin 1 and interleukin 2 generation by peripheral blood cells from patients with ankylosing spondylitis.

We examined the spontaneous secretion of interleukin 1 (IL-1) from peripheral blood monocytes and staphylococcal protein A (SPA) induced secretion of interleukin 2 (IL-2) from peripheral blood mononuclear cells from 13 patients with active ankylosing spondylitis and 10 healthy controls. IL-1 and IL-2 secretion in the patient group was not measurably different from controls (p greater than 0.05). We also examined IL-1 and IL-2 generation in 7 patients before and 2 months after therapy with a nonsteroidal antiinflammatory agent, piroxicam. A variable effect of piroxicam was observed on IL-1 and IL-2 generation despite the efficacy of piroxicam in reducing the clinical activity of the disease. Our results suggest the absence of an intrinsic aberration in IL generation from peripheral blood cells from patients with ankylosing spondylitis.

Adult

Nifedipine in the treatment of idiopathic Raynaud's syndrome.

Thirty-nine patients with idiopathic Raynaud's syndrome were randomized into a double-blind controlled trial comparing nifedipine 10 mg TID to placebo during the winter months between November, 1981 and March, 1983. The pills were doubled at 5 weeks in the absence of subjective improvement. Frequency and severity of vasospastic attacks were recorded in a diary. Over the 10-week treatment period, there was a 48.2% reduction in frequency of attacks in the nifedipine group compared to a 24.6% reduction in the placebo group (p less than 0.05). Treatment reduced the frequency of attacks by at least 30% in 10 of 15 patients. The severity of attacks was also significantly improved. Further, analysis suggests a trend towards diminished effectiveness over time. Side effects occurred in all patients taking nifedipine but were usually mild and well tolerated. Nifedipine is effective in reducing the frequency and severity of vasospastic attacks in idiopathic Raynaud's syndrome over a 10-week period.

Adult

Digital blood flow and nailfold capillary microscopy in Raynaud's phenomenon.

Digital blood flow was assessed by photoplethysmography, ultrasonic arterial flow tracing and measurement of systolic blood pressure, and compared to nailfold capillary microscopy in 20 normal controls, 16 patients with primary Raynaud's phenomenon, 40 with undifferentiated connective tissue disease and 30 with systemic sclerosis. All 4 measurements showed significant differences between controls, Raynaud's phenomenon and systemic sclerosis but only capillaroscopy (mean number of enlarged capillary loops and avascular score) was able to differentiate between primary Raynauds and undifferentiated connective tissue disease. Capillaroscopy (mean numbers of enlarged capillary loops) was the most sensitive (100%) and specific (81%) test with a positive predictive value of 90% for systemic sclerosis.

Adult

Impaired release of a T-cell specific suppressor factor in rheumatoid arthritis.

Peripheral blood T cells from patients with rheumatoid arthritis (RA) and scleroderma (PSS) were assessed for their ability to release T-cell-specific suppressor activity (TRSA) upon incubation with a suppressor activating factor (SAF) derived from a human lymphoblastoid cell line (CEM). T cells from 11/20 (55%) RA patients exhibited impaired TRSA release in contrast to 1/12 (8%) of PSS patients. RA patients demonstrating impaired TRSA release exhibited more active arthritis than patients demonstrating normal TRSA release.

Adult

Serologically active clinically quiescent systemic lupus erythematosus: a discordance between clinical and serologic features.

The significance of abnormal serologic tests in systemic lupus erythematosus (SLE) in the absence of active clinical disease is unclear. In this report we describe a group of 14 patients with SLE in whom a discordance between clinical and serologic features was apparent. These patients had persistently positive lupus erythematosus preparations and antinuclear antibody tests, low serum complement levels and high levels of DNA binding. Their lymphocyte response to concanavalin A (Con A) mitogen was suppressed. They have been asymptomatic and have remained untreated for a mean of four and a quarter years.

Adult

Leucapheresis in severe rheumatoid arthritis.

Two patients with severe seropositive rheumatoid arthritis previously unresponsive to conventional therapy have been treated with leucapheresis. This technique involves continuous cell separation daily to remove primarily lymphocytes. Clinical improvement was recorded with the use of standard rheumatological measures of inflammation. It is concluded that leucapheresis may help in the management of severely active rheumatoid arthritis when conventional therapy has been unsuccessful.

Adult

Effects of lymecycline on Mycoplasma pulmonis-induced arthritis in mice.

The effect of lymecycline treatment on arthritis in C3H mice produced 5 months previously by i.v. inoculation of Mycoplasma pulmonis was examined. Treatment had little effect on the severity of the clinical disease. However, there was a marked reduction the severity of the histopathological inflammatory reaction in joints from lymecycline-treated mice when compared with untreated controls. This reduction was associated with eradication of viable mycoplasmas from the joints. The findings suggest that persistent arthritis in C3H mice is due to the continued presence of viable M. pulmonis organisms in the joint tissues.

Animals

Inhibition of mitogen mediated lymphocyte blastogenesis by adenosine.

The effect of adenosine on the proliferative response of human peripheral circulating lymphocytes to stimulation by concanavalin A, phytohemagglutinin and pokeweed mitogen was evaluated. Increasing concentrations of adenosine substantially inhibited mitogen mediated lymphocyte blastogenesis. Erythro-9(2-hydroxyl-3-nonyl) adenine. HCl enhanced the inhibitory effect of adenosine. Inosine, the deamination product of adenosine, had an inhibitory effect which was less than that of adenosine. Inhibition by adenosine may be relevant to the normal regulation of immune function and may account in part for the pathophysiological relationship between severe combined immunodeficiency disease and adenosine deaminase deficiency.

Adenine

Mixed leukocyte reaction in rheumatoid arthritis.

The mixed leukocyte reaction (MLR) responses of 29 patients with classic rheumatoid arthritis (RA) were compared with those of 24 age- and sex-matched healthy controls. Pools of stimulating cells were selected to include the major cross-reacting HL-A specificities. In pooled human serum the MLR response of the RA lymphocytes was significantly enhanced relative to the response controls (P less than 0.05). In autologous serum there was suppression of the MLR response in patients with RA which correlated with disease activity. The data suggest the presence of an intrinsically enhanced cellular reactivity of RA lymphocytes suppressed by serologic factor(s). The mechanisms of this enhancement of suppression are discussed.

Adult

Zymosan-induced arthritis: a model of chronic proliferative arthritis following activation of the alternative pathway of complement.

Zymosan particles, which are able to activate complement by the alternative pathway and to induce enzyme secretion from macrophages, were injected into knee joints of mice. After various time intervals, synovia were assessed histologically for various markers of inflammation. Within 7 days after intraarticular injection of zymosan, a chronic inflammatory arthritis with mononuclear cell infiltration, synovial hypertrophy and pannus formation was observed. Latex particles, which do not activate complement or macrophages, produced only mild, transient inflammatory reactions.

Animals

Malignant pyoderma.

A patient with malignant pyoderma brought into complete remission with immunosuppressive cyclophosphamide treatment after the failure of multiple other therapies is reported. The entity of malignant pyoderma with its clinical characteristics, laboratory and biopsy findings, complications, and modalities of therapy is reviewed.

Adult