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Biomedical subjects

R B Zurier

Publications and source records attributed to R B Zurier.

At least 37 records · Page 2Linked to original sources
PubMed1994

Suppression of acute inflammation with liposome associated prostaglandin E1.

Prostaglandin E1 (PGE1) suppresses leucocyte effector function and reduces inflammation in several animal models of acute and chronic inflammation. A drawback to its use as a therapeutic agent is the relatively high doses needed to suppress inflammation. We present evidence in this report that liposome associated PGE1 (LAP) reduces markedly acute inflammation induced in a subcutaneous air pouch by monosodium urate crystals, and by the polypeptide mediators, interleukin 1-beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha). A single dose of 12 micrograms/kg LAP given intravenously 2 hr after inflammation was induced, reduced accumulation of cells and exudate by 31-49%.

Acute Disease↗
PubMed1994

Treatment of rheumatoid arthritis with blackcurrant seed oil.

The objective of this study was to assess the clinical efficacy and side effects of blackcurrant seed oil (BCSO), in a randomized, double-blind, placebo controlled, 24-week trial in patients with RA and active synovitis. BCSO is rich in gammalinolenic acid (GLA) and alphalinolenic acid (ALA). Both GLA and eicosapentaenoic acid which derives from ALA suppress inflammation and joint tissue injury in animal models. Treatment with BCSO resulted in reduction in signs and symptoms of disease activity in patients with RA (P < 0.05). In contrast, patients given a placebo showed no change in disease. Overall clinical responses (significant change in four measures) were no better in the treatment group than in the placebo group. No patients withdrew from BCSO treatment because of adverse reactions. However, many patients withdrew because BCSO and its placebo had to be administered in 15 large capsules daily. Nonetheless, the study indicates that BCSO is a potentially effective treatment for active RA. However, means must be found to reduce the size and number of capsules taken, so that larger studies of longer duration in RA patients can be done.

Adult↗
PubMed1993

Treatment of rheumatoid arthritis with gammalinolenic acid.

OBJECTIVE: To assess the clinical efficacy and side effects of gammalinolenic acid, a plant-seed-derived essential fatty acid that suppresses inflammation and joint tissue injury in animal models. DESIGN: A randomized, double-blind, placebo-controlled, 24-week trial. SETTING: Rheumatology clinic of a university hospital. PATIENTS: Thirty-seven patients with rheumatoid arthritis and active synovitis. INTERVENTION: Treatment with 1.4 g/d gammalinolenic acid in borage seed oil or cotton seed oil (placebo). MEASUREMENTS: Physicians' and patients' global assessment of disease activity; joint tenderness, joint swelling, morning stiffness, grip strength, and ability to do daily activities. RESULTS: Treatment with gammalinolenic acid resulted in clinically important reduction in the signs and symptoms of disease activity in patients with rheumatoid arthritis (P < 0.05). In contrast, patients given a placebo showed no change or showed worsening of disease. Gammalinolenic acid reduced the number of tender joints by 36%, the tender joint score by 45%, swollen joint count by 28%, and the swollen joint score by 41%, whereas the placebo group did not show significant improvement in any measure. Overall clinical responses (significant change in four measures) were also better in the treatment group (P < 0.05). No patients withdrew from gammalinolenic acid treatment because of adverse reactions. CONCLUSION: Gammalinolenic acid in doses used in this study is a well-tolerated and effective treatment for active rheumatoid arthritis. Gammalinolenic acid is available worldwide as a component of evening primrose and borage seed oils. It is usually taken in far lower doses than used in this trial. It is not approved in the United States for the treatment of any condition and should not be viewed as therapy for any disease. Further controlled studies of its use in rheumatoid arthritis are warranted.

Adult↗
PubMed1993

Fatty acids, inflammation and immune responses.

Evidence obtained from experiments in vitro and in vivo suggests that certain unsaturated fatty acids (FA) may be safe and effective antiinflammatory and immunomodulatory agents. Generation of a unique eicosanoid profile with different biological effects by administration of FA precursors other than arachidonic acid is one approach under investigation. In addition to their role as eicosanoid precursors, FA are of major importance in maintaining cell membrane structure, are key determinants of membrane bound enzyme activity and receptor expression. FA can exert these functions directly and therefore may themselves be important regulators of immune responses. For example, certain FA influence cytokine production and proliferation of human T lymphocytes in a manner that is direct and not due to their conversion to eicosanoids. The observations indicate that FA can modulate immune responses by acting directly on T-cells and suggest that alteration of cellular FA may be a worthwhile approach to control of inflammation.

8,11,14-Eicosatrienoic Acid↗
PubMed1992

Molecular diagnosis of Ureaplasma urealyticum septic arthritis in a patient with hypogammaglobulinemia.

OBJECTIVE: We report a hypogammaglobulinemic patient with a destructive oligoarticular arthritis, whose synovial fluid cultures were repeatedly sterile. METHODS AND RESULTS: We identified a Ureaplasma urealyticum infection in his affected joints, using a polymerase chain reaction (PCR) assay. CONCLUSION: The PCR technique promises to be extremely valuable in the rapid and specific diagnosis of infectious arthritis.

Adult↗
PubMed1992

Effects of polyunsaturated fatty acids on interleukin-2-dependent T cell growth.

Cellular membranes, in addition to serving as structural constituents of cells, also provide precursors for a number of chemical messengers involved in intracellular signal transduction. This includes the eicosanoids (prostaglandins and leukotrienes) and diacylglycerol, and activator of protein kinase C (PKC). Changes induced in the fatty acid profile of lymphocytes can influence vital metabolic processes in cells. Such changes, independent of the function of fatty acids as prostaglandin and leukotriene precursors, can alter the development and regulation of immune responses. In this report we study the effects of the polyunsaturated fatty acids (PUFA) on proliferation and signal transduction in the interleukin-2 (IL-2)-dependent murine T cell line CTL.L-2. Culture of CTL.L-2 cells in the presence of specific PUFA resulted in their incorporation into the cellular phospholipids. IL-2-induced proliferation of CTL.L-2 cells was markedly suppressed in a dose-dependent fashion by incubation in media supplemented with dihomogammalinolenic acid (an n-6 PUFA) slightly inhibited proliferation, while eicosapentaenoic acid (an n-3 PUFA) had no effect. Neither indomethacin (a cyclooxygenase inhibitor) nor nordihydroguaiaretic acid (NDGA, a lipoxygenase inhibitor) reversed the effect of DGLA. In contrast, phorbol 12-myristate 13-acetate (a phorbol ester and activator of PKC), blocked, in a dose-dependent manner, the antiproliferative effect of DGLA. This study presents evidence that PUFA alter signal transduction in cells in a manner which is separate from their function as eicosanoid precursors. The botanical lipid-derived DGLA has a potent suppressive effect on IL-2-driven T cell proliferation and may alter signal transduction by modification of second messenger or PKC activity.

Animals↗
PubMed1992

Restricted heterogeneity of T cell receptor transcripts in rheumatoid synovium.

RA is characterized by massive proliferation of synovial tissue, accompanying infiltration of the tissue with CD4+ T lymphocytes, and a genetic linkage to the MHC antigen HLA-DR4. Since T cells are restricted by class II MHC molecules such as DR4, this suggests a direct role for these CD4+ cells in pathogenesis. To investigate T cell receptor (TCR) usage in RA, we used oligonucleotide primers specific for each of the major alpha and beta TCR subfamilies to amplify cDNA derived from whole synovium or synovial tissue T cell lines in a family-specific manner. Detection of amplified DNA was facilitated by utilizing oligonucleotide probes derived from the constant regions of the TCRs. The TCR repertoire present in the synovial T cell lines was quite heterogeneous, with an average of 15 alpha chains and 15.8 beta chains detected. When synovial tissue was analyzed, the predominant TCR subfamilies detected tended to be more restricted, with an average of 4.6 alpha chains and 8.6 beta chains detected. This compared with an average of six alpha chains and 12 beta chains in nonrheumatoid synovial samples. The average percentage of synovia positive per TCR beta family was significantly lower for RA versus non-RA specimens (46.1 vs 65.6%, P = 0.034). These findings indicate that while a polyclonal population of T cells is present in RA synovium, the predominant patterns of TCR transcript expression may be somewhat more restricted, suggesting that TCR-based therapy of RA is possible.

Arthritis, Rheumatoid↗
PubMed1991

Interleukin-1 induced gene expression of neutrophil activating protein (interleukin-8) and monocyte chemotactic peptide in human synovial cells.

We report here that human synovial cells stimulated by interleukin-1 alpha and interleukin-1 beta express mRNA for both IL-8 (neutrophil chemotactic peptide) and monocyte chemotactic protein. IL-1 stimulated synovial cells from both osteoarthritis and rheumatoid arthritis patients exhibited similar mRNA expression of interleukin-8 and monocyte chemotactic protein. A capacity to produce factors selectively chemotactic for neutrophils, lymphocytes and monocytes provides a mechanism whereby synovial cells can facilitate inflammatory arthritis.

Blotting, Northern↗
PubMed1991

Treatment of rheumatoid arthritis.

Rheumatoid arthritis is a chronic inflammatory disease that results in progressive disability and increased mortality. New therapeutic strategies are being recommended to initiate, earlier than in the past, more aggressive use of disease-modifying drugs in an effort to reduce joint destruction. In this article, the results of recent clinical trials with nonsteroidal anti-inflammatory drugs, intravenous "pulse" corticosteroids, and standard disease-modifying drugs are reviewed. In addition, preliminary results of trials with new experimental therapies, such as botanical and marine lipids, interferon-gamma, and monoclonal antibodies directed against leukocyte cell surface markers are discussed.

Adrenal Cortex Hormones↗
PubMed1991

Botanical lipids: potential role in modulation of immunologic responses and inflammatory reactions.

Enrichment of cells with fatty acids of particular botanical lipids alters cell function in vitro (for example, suppression of human synovial cell and T lymphocyte proliferation) in a manner that suggests that administration of these botanical lipids may be a useful therapeutic strategy for patients with diseases characterized by disordered immune responses and chronic inflammation. Treatment of animal models with certain plant seed oils suppresses inflammation and joint tissue injury. Controlled trials in patients with rheumatoid arthritis are in an early stage, but offer encouragement. The mechanisms whereby these novel lipids influence host defense include alteration of arachidonic acid oxygenation products and direct effects on cells independent of fatty acid metabolism.

Animals↗
PubMed1990

Alteration of the cellular fatty acid profile and the production of eicosanoids in human monocytes by gamma-linolenic acid.

We administered borage seed oil (9 capsules/day) for 12 weeks to 7 normal controls and to 7 patients with active rheumatoid arthritis. The therapy provided 1.1 gm/day of gamma-linolenic acid (GLA). GLA administration resulted in increased proportions of its first metabolite, dihomo-gamma-linolenic acid (DGLA), in circulating mononuclear cells. The ratios of DGLA to arachidonic acid and DGLA to stearic acid increased significantly in these cells. Significant reductions in prostaglandin E2, leukotriene B4, and leukotriene C4 produced by stimulated monocytes were seen after 12 weeks of GLA supplementation. The antiinflammatory effects of GLA administration observed in animal models, and the apparent clinical improvement experienced by 6 or 7 rheumatoid arthritis patients given borage seed oil in this open, uncontrolled study may be due in part to reduced generation of arachidonic acid oxygenation products.

Administration, Oral↗
PubMed1990

Suppression of interleukin 2-dependent human T cell growth in vitro by prostaglandin E (PGE) and their precursor fatty acids. Evidence for a PGE-independent mechanism of inhibition by the fatty acids.

PGE represent oxygenation products of polyunsaturated essential fatty acids and are important regulators of cell-mediated immune responses. Because oils enriched in such fatty acids reduce inflammation and tissue injury in vivo, we examined the effects of these PGE precursors on IL-2-driven growth of human T lymphocytes. Dihomogamma linoleic acid (DGLA), AA, and their metabolites (PGE1 and PGE2, respectively) strongly inhibited short- and long-term growth of IL-2-dependent T cell cultures; EPA was much less inhibitory and its product, PGE3, failed to suppress IL-2 responses. Short-term pretreatment of the cells with DGLA or AA and removal of the fatty acids before the proliferation assay resulted in a smaller reduction in [3H]TdR incorporation. PGE and fatty acids did not alter the number of high affinity IL-2 binding sites on the T cell cultures but reduced the percentage of cells expressing CD25 and HLA class II molecules. No PGE was detected in supernatants from the fatty acid-treated cultures. Moreover, indomethacin, a cyclooxygenase inhibitor, did not reverse the antiproliferative effects of the fatty acids. Together, these findings indicate that fatty acids can inhibit IL-2-driven T cell growth via a PGE-independent mechanism and might be relevant to inflammatory diseases associated with persistent T cell activation.

Antigens, CD↗
PubMed1990

Antinuclear antibody in pericardial fluid from a patient with primary cardiac lymphoma.

Pericarditis may be the initial manifestation of systemic lupus erythematosus. Although it is known that antinuclear antibody can be detected in the serum of patients with a wide variety of diseases, it has been proposed that the detection of antinuclear antibody in serosal fluid is a sensitive and specific test for determining that effusions are due to systemic lupus erythematosus. A case is presented in which antinuclear antibody in high titer was identified in the pericardial fluid of a patient who was found at autopsy to have a primary cardiac lymphoma. The case indicates that antinuclear antibody detected in serosal effusions should not be considered pathognomonic for systemic lupus erythematosus.

Aged↗
PubMed1989

Prostaglandin E precursor fatty acids inhibit human IL-2 production by a prostaglandin E-independent mechanism.

Essential fatty acids, from which PG derive, can participate in development and regulation of immune responses and have been shown to suppress inflammation and tissue injury in animal models. In this report, we investigate the effects of the immediate (DGLA, precursor to PGE1), arachidonic acid (AA, PGE precursors, dihomogamma linolenic acid (DGLA, precursor to PGE1), arachidonic acid (AA, precursor to PGE2), and eicosapentaenoic acid (EPA, precursor to PGE3) on IL-2 production by PHA-stimulated human PBMC. DGLA and AA inhibited IL-2 production in a dose-dependent manner: half-maximal inhibition was obtained by using the fatty acids at the dose of 10 micrograms/ml without significant effects on cell viability. EPA inhibited IL-2 production by PBMC of only some donors. Incubation of cells in the presence of oleic, stearic, and palmitic acids, which are not PG precursors, did not affect mitogen-induced IL-2 production. A progressive increase in incorporation of DGLA into cellular lipids was observed over a 48-h incubation period. IL-2 production was reduced also when PBMC were pretreated overnight with DGLA or AA and washed before exposure to PHA. Whereas addition of the cyclo-oxygenase inhibitor, indomethacin, at the time of mitogenic stimulation led to increased IL-2 production and prevented mitogen- and fatty acid-induced increases in PGE release, it had no significant effect on the capacity of the fatty acids to suppress IL-2 production. Time course experiments showed that DGLA and AA inhibited IL-2 production even at times of minimal or no PGE release by the treated cultures. Moreover, DGLA and AA inhibited IL-2 production by the human leukemia T cell line Jurkat which, when appropriately induced, is able to release high levels of IL-2 in the absence of accessory cells and measurable PGE production. Taken together, these data indicate that essential fatty acids inhibit IL-2 production directly without conversion into their cyclo-oxygenase pathway products, and suggest that human lymphocyte function may be altered profoundly by small changes in their fatty acid profile.

Arachidonic Acid↗