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Biomedical subjects

R S Panush

Publications and source records attributed to R S Panush.

At least 109 records · Page 6Linked to original sources

Diet therapy for rheumatoid arthritis.

Although diet therapy for arthritis has received considerable publicity, there is little objective information about its efficacy. We undertook a 10-week, controlled, double-blind, randomized trial of patients with active rheumatoid arthritis (RA). Twenty-six patients completed the study; 11 were on an experimental diet (a specific popular diet free of additives, preservatives, fruit, red meat, herbs, and dairy products) and 15 were on a "placebo" diet. Of 183 variables analyzed, there were no clinically important differences among rheumatologic, laboratory, immunologic, radiologic, or nutritional findings between patients on experimental and placebo diets. Six RA patients on the placebo and 5 on the experimental diet improved by objective criteria. Improvement averaged 29% for patients on placebo and 32% for patients on experimental diets. Two patients on the experimental diet improved notably, elected to remain on the experimental diet following the study period, have continued to improve, and noted exacerbations of disease upon consuming nonexperimental diet foods. Our study failed to provide evidence of objective overall clinical benefit of this diet as followed by a group of patients with longstanding, progressive, active RA. However, our data are not inconsistent with the possibility that individualized dietary manipulations might be beneficial for selected patients with rheumatic disease.

Arthritis, Rheumatoid↗

Modulation of human mononuclear cell responses by neutrophil-derived factors. II. Partial characterization of a neutrophil-derived lymphocyte-enhancing factor (N-LEF).

We previously reported that neutrophil (PMN)-derived factors modulated human mononuclear cell (MNC) responses. These interactions are important in understanding MNC localization, growth, and activation in inflammatory events such as occur in the rheumatoid synovium. We have partially identified and characterized a human neutrophil-derived, lymphocyte-enhancing factor (N-LEF). Highly purified PMN, devoid of MNC or platelets, were obtained by density gradient sedimentation. Supernatants (spt) were prepared from PMN phagocytosis of complement-coated zymosan particles. N-LEF was determined by [3H]TdR uptake or Ig secretion by stimulated MNC of cell lines. Neutral protease activity was quantitated by digestion of 125I-labeled Hb. Sodium dodecylsulfate (SDS) polyacrylamide gel electropheresis (PAGE) was carried out in 15% gels. We found (1) N-LEF biologic activity was cold stable, heat labile, nondialyzable, and diminished at acid pH (less than 4) or alkaline pH (greater than 10); (2) N-LEF biologic activity was abrogated by human plasma; (3) spt contained neutral protease and granule-associated but not cytoplasmic enzyme activities; (4) protease activities (for Hb, fibrin, ATEE, and Ac-Phe-BNa) were recovered from aprotinin-sepharose affinity columns and contained approximately 25,000 and approximately 28,000 molecular weight material on SDS-PAGE; (5) absorbtion of N-LEF spt on aprotinin-sepharose diminished both protease and biologic activities; and (6) N-LEF biologic activity and nonelastase neutral protease activity were found in approximately 13,000 mol wt fractions of Sephadex G100 (where cathepsin G chromatographs). Our observations suggest that phagocytosis of immune complexes by PMN induces release of a mononuclear cell enhancing factor, N-LEF, which may be an important mediator of inflammation, promoting transition from an acute to a chronic inflammatory response. Biologic properties of N-LEF are those of cathepsin G.

Antimicrobial Cationic Peptides↗

Rheumatoid vasculitis: diagnostic and therapeutic decisions.

Rheumatoid vasculitis is an uncommon but potentially catastrophic complication of RA. There are few extensive experiences recorded in the current literature and there is no consensus regarding the clinical features, laboratory findings, histologic pattern, prognosis, or appropriate management of this syndrome. We therefore surveyed 1,947 North American ARA members for their perceptions of rheumatoid vasculitis. Four hundred twenty-eight surveys were returned, of which 290 were suitable for analysis. The majority of respondents were within 10 years of fellowships and were evenly distributed among private practice, and part-time and full-time academic positions. The respondents saw 15-50 rheumatoid arthritis (RA) patients weekly and less than five RA vasculitis patients annually. The majority correctly diagnosed two actual and complex case histories from patients with and without autopsy-proven vasculitis. Respondents associated the following features most strongly with rheumatoid vasculitis - mononeuritis multiplex, digital gangrene, digital ischemic lesions, nailfold ischemic lesions, non-healing leg ulcers, palpable purpura, fingertip nodules, sensory neuropathy, scleromalacia perforans, high titer rheumatoid factor, positive visceral angiography, cryoglobulinemia, hypocomplementemia, circulating immune complexes, and histologic necrotizing vasculitis or vascular transmural neutrophilia. Digital lesions or sensory neuropathy alone were not viewed as portending an ominous prognosis by most respondents and would have been treated with nonsteroidal anti-inflammatory drugs, antimalarials, gold salts, or D-penicillamine. Other clinical manifestations considered as reflecting rheumatoid vasculitis (gangrene, mononeuritis multiplex, ulcers) were thought to worsen prognosis and would have been managed more often with corticosteroids, D-penicillamine, cytotoxic agents or plasmapheresis. Rheumatoid vasculitis is viewed as a heterogeneous group of syndromes with varying clinical and histopathologic features,which have different prognostic implications, and therefore should be managed differently. While these dta do not substitute for an extensive recorded series of patients, they provide useful information about community perceptions of an uncommon but difficult clinical problem. They identify the need for additional data to examine the validity of these attitudes.

Arthritis, Rheumatoid↗

In vitro immunoglobulin production by mononuclear cells in rheumatoid arthritis.

Since patients with rheumatoid arthritis (RA) exhibit serum hypergammaglobulinemia and autoantibody (rheumatoid factor) production, we compared elaboration and control of in vitro RA mononuclear cell (MNC), Ig assayed by enzyme-linked immunoassays or by hemolytic plaque formation, in 37 RA patients and 17 normal subjects. We found (1) RA spontaneous plaque-forming cells were significantly reduced (RA 344 vs normal 627 PFC/10(6) MNC, P less than 0.002); (2) RA spontaneous IgG and IgM (but not IgA) elaboration was significantly diminished (IgG RA 339, normal 776; IgM RA 255, normal 869 ng/ml, P less than 0.001; IgA RA 87, normal 124); (3) RA stimulated IgG and IgM production (but not IgA) was also decreased (IgG RA 2434, normal 3862, P less than 0.06; IgM RA, 1676, normal 3323, P less than 0.005; IgA RA 1859, normal 2315); (4) reduced RA Ig elaboration was not clearly due to altered numbers of T or non-T cells, age, medications, clinical features of disease, or response kinetics; (5) relative improvement of RA in vitro IgG, but not usually IgM, secretion followed removal of adherent cells, addition of indomethacin or addition of mitomycin C-treated T cells; (6) MNC from synovial fluids, but not bone marrows, exhibited spontaneous Ig production in excess of stimulated synovial fluid cellular or peripheral blood Ig elaboration. These observations indicate selective impairment of peripheral blood MNC IgG and, particularly, IgM secretion in RA. This defect appears to reflect accessory cell influences which differ from normal as well as the sequestration of primed or activated cells in the synovial fluid.

Adult↗

Viral arthritis.

Explore the source record for details and available documents.

Adolescent↗

An enzyme-linked immunoassay for detection of IgG- and C3-containing circulating immune complexes: comparison with a radioimmunoassay and quantitation in patients with rheumatic diseases.

We developed a simplified, relatively rapid, inexpensive, antigen-nonspecific, enzyme-linked immunosorbent assay (ELISA) for immunoglobulin G (IgG)- and C3-containing circulating immune complexes (CICs), adapted from a solid-phase anti-C3 radioimmunoassay (RIA). Standards (containing purified, heat-aggregated IgG and fresh human serum) or samples were allowed to react with goat F(ab')2 antihuman C3 bound to the matrix of microtiter plates. Then alkaline phosphatase conjugated to goat IgG fraction antihuman IgG was added, followed by p-nitrophenylphosphate, optical densities determined, and concentrations of CICs calculated. We found excellent correlations between serum and plasma CIC levels by either ELISA (r = 0.95, p less than 0.01) or RIA (r = 0.89, p less than 0.01). Furthermore, ELISA quantitation of CICs correlated well with RIA (serum, n = 75, r = 0.64, p less than 0.01; plasma, n = 101, r = 0.56, p less than 0.01). By ELISA we found 32 normal subjects had 38 +/- 12 micrograms CIC/ml in serum and 34 +/- 10 micrograms CIC/ml in plasma. Patients with systemic lupus erythematosus (39% of 27 patients, p less than 0.05) had significantly elevated CIC levels compared with normal (serum, 157 +/- 50 micrograms/ml, p less than 0.01; plasma, 89 +/- 23 micrograms/ml, p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Antibody Complex↗

Assessment of the diet of patients with rheumatoid arthritis and osteoarthritis.

There have been many and divergent thoughts expressed both in the scientific and in the lay literature regarding diets for patients with arthritis (1-8). However, few experimental observations pertain to either the nutritional status of arthritis patients or the clinical value of putative nutritional therapies (1-8). Until such time as the notion that dietary manipulation can alleviate particular symptoms for selected patients is proved, it is prudent to advise patients to maintain sound nutritional practices in accordance with contemporary standards (4-8, 13-16). Our data indicate that many arthritis patients are at least marginally inadequate in selected nutrients, some of which (vitamin E and zinc) might relate to immunologic events important in perpetuating the disease. These observations provide a basis for nutritional counseling of arthritis patients.

Adolescent↗

Nonspecific suppressor function in rheumatoid arthritis.

Patients with rheumatoid arthritis (RA) have diminished peripheral blood cellular immune responses in vivo and in vitro. To determine whether these changes reflected excessive peripheral blood suppressor function, we compared suppressor function in 52 patients with RA with 57 normal subjects. We examined suppressor cell function for (i) preincubation sensitivity, (ii) glass adherence, (iii) indomethacin sensitivity, (iv) concanavalin (con) A inducibility, (v) aggregated IgG inducibility and (vi) quantitated Tmu and Tgamma cell populations. Con A-generated suppressor cell function was further studied by evaluating unseparated-, T-cell, glass adherent-, indomethacin sensitive-, radiosensitive-, and radioresistant-suppressor cell effects upon mitogen-stimulated allogeneic and autologous unseparated, T-cell, B-cell and IM9 lymphoblastoid cell line responses, the latter representing a newly devised and simplified assay system. We found that patients with RA exhibited: (i) significantly increased incubation-sensitive suppressor function; (ii) generally normal nonspecific suppression function in other assays, although individual patients were strikingly abnormal; and (iii) significantly increased sensitivity of B-cell proliferation to aggregated-IgG-induced T-cell suppressor function.

Arthritis, Rheumatoid↗

A new, simplified assay for suppressor cell function.

A simplified, sensitive assay has been devised to examine suppressor cell function in normal persons and patients with rheumatic and atopic diseases. Cultured human lymphoblastoid (IM9) cells were used as responders. Induced suppressor cells were treated initially with mitomycin (mit) C, to prevent DNA synthesis, then incubated with concanavalin (con) A in microtiter plates for 40 hr. Responder cells were added directly to suppressor cells in plates. Suppression was determined by comparing effects of con A-induced with noninduced (control) cells on responder 3H-thymidine (3HTdR) uptake. This assay is simple and conserves time, reagents, and cells and uses standardized, available responder cells. It also obviates problems of con A in cultures with responder cells and autologous or allogeneic mixed-lymphocyte types of reactions and reduces needs for blood donation. Moreover, IM9 cells proved suitable for detecting spontaneous, con A-generated, glass-adherent, or prostaglandin-secreting (indomethacin-sensitive) suppressor cells.

Arthritis, Rheumatoid↗

Modulation of lymphocyte proliferative responses to mitogens and antigens by complement components C1, C4 and C2.

Recent data have shown a definite relationship between complement and lymphocytes. Genetic studies have demonstrated close linkage between the genes controlling synthesis of complement components C4 and C2 and the major histocompatibility complex. Working in a complement-free environment, we studied the effect of purified human complement components, individually and in various combinations, upon in vitro proliferative responses of human lymphocytes to mitogens and antigens. It was found that the early complement components C1, C4 and C2, together, modulate lymphocyte responses to these various stimuli. In general, doses up to 1,000 effective molecules of each component per lymphocyte enhanced the cells' responses to both mitogens and antigens. Higher doses, up to 3,000 effective molecules of each per lymphocyte, progressively inhibited the cells' responses to the mitogens whereas responses to the antigens showed continued enhancement. This effect was removed by prior heat-inactivation of the complement. It persisted when the cells were exposed to C1, C4 and C2 for 1 hr, then washed and cultured with mitogen. It required active C1 in the fluid-phase prior to addition of C4 and C2. It correlated with the amount of activated C2 to which the cells were exposed. Enriched populations of T and B cells were affected equally.

Antigens↗

Abnormal natural killer cell activity in systemic lupus erythematosus: an intrinsic defect in the lytic event.

The natural killer (NK) cell activity in fifteen systemic lupus erythematosus (SLE) patients was investigated by employing 51-chromium- (51Cr) release microcytotoxicity and single cell cytotoxicity assays against K562 target cells. Although the SLE patients as a group had depressed NK function in the 51Cr-release assay compared to normal subjects (p less than 0.005), those with clinically active disease displayed the greatest impairment in this activity (p less than 0.001). Active SLE patients were deficient in overall NK activity (Vmax) (p less than 0.005) but had normal percentages of potentially cytotoxic target binding cells (TBC). These TBC, however, were unable to normally kill bound target cells (p less than 0.01), which is indicative of a deficiency of "active" NK cells (p less than 0.005). Those NK cells with intact cytotoxic capabilities could "recycle" and repeat the lytic sequence normally. Exposure of normal lymphocytes to SLE sera did not impair any phase of NK function. These studies indicate that defective NK activity in SLE is secondary to an abnormality in the lytic event itself and is not due to a deficiency of NK cells, an abnormality in target binding, or an inability of NK cells to lyse multiple targets. Additionally, serum factors do not appear to play a major etiologic role in the cytotoxic abnormalities of these patients.

Adolescent↗

Modulation of human lymphocyte responses by neutrophil-derived factors: effects of neutrophils and neutrophil-derived factos.

Lymphocytes and polymorphonuclear neutrophils (PMNs) occur together in inflammatory sites. We have examined the possibility that PMNs, or PMN-derived factors, might influence human peripheral blood lymphocyte (PBL) functions. PBL were cultured with or without antigen or phytomitogen, and with or without purified PMNs, PMN lysates or supernatants (SPTs) from PMNs that had phagocytized zymosan-complement complexes. PMN-derived enhancing and inhibitory activities were identified. Studies indicated: (1) PMNs exhibited concentration-dependent enhancement or inhibition of PVL methyl-3H-thymidine uptake; (2) lysates of PMNs similarly inhibited PBLs at high concentrations, enhanced with dilution, and inhibited with further dilution; (3) SPTs from PMN that had phagocytized zymosan-complement also exhibited concentration-dependent enhancement and inhibition; (4) inhibition did not result from (a) mitogen binding or inactivation, (b) exhaustion of in vitro nutrients, (c) change of expected kinetics of responses, (d) alterations of cell numbers or viability; (5) enhancement and inhibition of PBL persisted after exposure to PMN SPT and washing before stimulation; and (6) PMN SPTs increased PBL ability to rosette with sheep erythrocytes. These observations identified two or more PMN-derived factors that may be important in modulating lymphocyte responses in acute and chronic inflammation.

B-Lymphocytes↗

Suppressor cell function in atopic diseases.

Atopic diseases are often characterized by high IgE levels and impaired cellular immune function. Defects in regulatory immune mechanisms have been identified in many other immunologic diseases. The authors examined non-specific spontaneous and concanavalin A generated suppressor function in 15 atopic patients using a new, simplified assay for suppressor cell function. Although three patients exhibited high spontaneous but little con A induced suppressor cell activity, there was no over-all difference in suppression between the atopic and normal control groups.

Adult↗