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ID PMID Title PublicationDate abstract
11096446 Adeno-associated virus production of soluble tumor necrosis factor receptor neutralizes tu 2000 Nov 20 The major limitation of adenovirus is its association with induction of an inflammatory response and relatively short-term production of the gene therapy transgene product. Adeno-associated virus (AAV) is a 4.68-kb single-strand DNA virus that contains ITRs for viral replication and a packaging signal, and also has been engineered to contain therapeutic genes up to 5 kb in length. Transduction of recombinant AAV (rAAV) results in low inflammatory response and long-term expression. We have cloned a low-immunogenic form of human sTNFRI (sTNFRI2.6D) into AAV (rAAVsTNFRI). This vector was analyzed for its ability to transfect and neutralize the effect of TNF-alpha on primary rheumatoid arthritis synovial fibroblast (RASFs). The rAAVsTNFRI was transduced into the cells at 1.8 x 10(1), 1.8 x 10(2), and 1.8 x 10(3) viral particles per cell. There was greater than 90% neutralization of TNF-alpha at 1.8 x 10(3) viral particles/cell. There was a significant decrease in the synovial cell hyperplasia and cartilage and bone destruction in human TNF-alpha transgenic mice treated intraarticularly with rAAVsTNFRI. These results indicate that the low-immunogenic and long-term expressing vector, rAAVsTNFRI, can be used to deliver the soluble TNF-alpha in vitro and in vivo and effectively reduce the severity of arthritis.
9755773 The triceps preserving approach to total elbow arthroplasty. 1998 Sep Elbow arthroplasty most commonly is performed through a posterior approach by detaching or reflecting the triceps off the olecranon. Surgical approaches to the elbow joint that dissociate the triceps from the olecranon have distinct disadvantages. Triceps avulsion, triceps weakness, and wound healing problems have been reported. Such complications necessitate more surgery and predispose the joint to an infection. To avoid these complications a modified posterior approach to the elbow joint that preserves the triceps muscle insertion on the olecranon was used in 10 consecutive elbow arthroplasties. This method provides adequate exposure, allows early rehabilitation, and avoids triceps weakness.
9226412 Aceclofenac blocks prostaglandin E2 production following its intracellular conversion into 1997 Jun 25 Aceclofenac, 2-[(2,6-dichlorophenyl) amino] phenylacetoxyacetic acid, is a novel non-steroidal anti-inflammatory drug. We investigated the effects of aceclofenac on prostaglandin E2 production by several kinds of human cells. Aceclofenac inhibited interleukin-1beta-induced prostaglandin E2 production by human rheumatoid synovial cells, but had no inhibitory effect on cyclooxygenase-1 or cyclooxygenase-2 activities by itself. We also observed that part of the aceclofenac was converted into diclofenac, the cyclooxygenase-1 and cyclooxygenase-2 inhibitor, when aceclofenac was incubated with human rheumatoid synovial cells. Aceclofenac was also converted into diclofenac and 4'-hydroxy diclofenac by human polymorphonuclear leukocytes and monocytes. 4'-Hydroxy diclofenac suppressed prostaglandin E2 production specifically by blocking cyclooxygenase-2 activity. These findings suggested that aceclofenac can be metabolized to cyclooxygenase inhibitors (diclofenac and/or 4'-hydroxy diclofenac) by these inflammatory cells. Although detailed examinations in non-inflammatory cells remain to be studied, we concluded that aceclofenac is shown to be a new type of non-steroidal anti-inflammatory drug which is intracellulary converted into active metabolites that inhibit the prostaglandin E2 production.
11141640 Sjögren syndrome. 2000 Dec Sjögren syndrome is a chronic systemic disease characterized by polyglandular tissue destruction leading to keratoconjunctivitis sicca (KCS) and xerostomia. Patients with primary Sjögren syndrome show evidence of KCS and xerostomia, whereas patients with secondary Sjögren syndrome suffer from KCS, xerostomia, and an autoimmune disease, most commonly rheumatoid arthritis. Certain factors cause autoimmune dysregulation leading to destruction of the acinar cells and ductal epithelia with subsequent dry eyes and dry mouth. Activated lymphocytes in patients with autoimmune diseases appear to have selective homing into the lacrimal and salivary glands leading to tissue damage. Understanding the factors involved in the immune dysregulation may improve our diagnostic and therapeutic approaches in Sjögren syndrome. Current therapeutic measures include means to increase secretion, relieve symptoms, and repair damage of the ocular surface.
11160154 Fibroblast-like synoviocytes support B-cell pseudoemperipolesis via a stromal cell-derived 2001 Feb B-cell accumulation and formation of ectopic germinal centers are characteristic changes in the diseased joints of patients with rheumatoid arthritis (RA). Earlier studies suggested that interactions between B lymphocytes and specialized synovial "nurse-like" cells peculiar to the RA synovium may be responsible for the homing and sustained survival of B cells in the synovium. However, in this study, we found that B cells spontaneously migrate beneath ordinary fibroblast-like synoviocytes (FLSs) and then experience prolonged survival. FLSs isolated from joints of patients with osteoarthritis also supported this activity, termed B-cell pseudoemperipolesis. We found that FLSs constitutively expressed the chemokine stromal cell-derived factor-1 (SDF-1), and that pertussis toxin or antibodies to the SDF-1 receptor (CXCR4) could inhibit B-cell pseudoemperipolesis. However, expression of SDF-1 is not sufficient, as dermal fibroblasts also expressed this chemokine but were unable to support B-cell pseudoemperipolesis unless previously stimulated with IL-4 to express CD106 (VCAM-1), a ligand for the alpha(4)beta(1) integrin, very-late-antigen-4 (VLA-4 or CD49d). Furthermore, mAb's specific for CD49d and CD106, or the synthetic CS1 fibronectin peptide, could inhibit B-cell pseudoemperipolesis. We conclude that ordinary FLSs can support B-cell pseudoemperipolesis via a mechanism dependent upon fibroblast expression of SDF-1 and CD106.
10660143 Blood levels of CD11b+ memory T lymphocytes are selectively upregulated in patients with a 1999 Dec The adhesion molecules CD11b (a beta2-integrin component) and CD54 (ICAM-1) on blood leukocytes were studied by flow cytometry in patients with rheumatoid arthritis (RA). The fractions of CD4+ cells co-expressing CD11b were elevated in 16 patients with active RA compared with those in 16 RA patients who improved during therapy and 8 healthy controls: 0.8+/-0.12% (mean+/-SEM) versus 0.3+/-0.06% (p<0.002) and 0.3+/-0.06% (p<0.005), respectively. Increased levels of CD11b+CD45R0+ cells were observed in patients with active RA compared to those with improved RA and controls: 12.6+/-3.9% versus 4.8+/-2.7% (p<0.002) and 6.1+/-1.2% (p<0.003), respectively. Disease activity, determined by C-reactive protein, correlated with the numbers of CD11b+CD45R0+ cells: r=0.62 (p<0.001). Seven patients were followed during induction of remission with methotrexate and glucocorticoids. The numbers of CD11b+CD4+ and CD11b+CD45R0+ cells fell significantly after clinical improvement. The levels of CD11b+CD14+ cells (monocytes) did not differ between the groups. The number of CD11b+CD15+ cells (neutrophils) was elevated in patients with RA irrespective of disease activity. The levels of CD54+ cells were not different between the RA and control groups. We conclude that the increased numbers of CD11b+ memory T cells may arise from exposure to stimuli outside the synovial compartment.
11669151 Anti-Human type II collagen CD19+ B cells are present in patients with rheumatoid arthriti 2001 Oct OBJECTIVE: To determine the frequency and repertoire of CD19+ B cells capable of producing antibodies reactive to type II collagen (CII) in synovial fluid (SF) and peripheral blood (PB) of patients with rheumatoid arthritis (RA) and PB of healthy control individuals. METHODS: CD19+ B cells were isolated and activated to secrete immunoglobulins (Ig) by CD4+ T cells. Frequencies of anti-CII B cells were determined by limiting dilution analysis. The isotype and cross-reactivity of the antibodies produced were determined by ELISA. RESULTS: SF and PB from 5 patients and PB from 4 healthy controls were analyzed. Anti-CII CD19+ B cells were identified in all samples tested. In the RA SF, the percentage of activated B cells reactive to human CII was significantly higher than in the PB of patients with RA (p < 0.05) or controls (p < 0.01). A majority of anti-human CII B cells from patients' SF secreted IgG isotype, whereas most anti-human CII B cells in PB of patients and controls secreted IgM. The anti-CII B cells, regardless of source, are usually reactive to both native and denatured human CII, to different types of human collagens, and to type II collagens from different species. CONCLUSION: Anti-CII CD19+ B cells responsive to activated helper T cells are present in both patients with RA and healthy individuals. However, these B cells, especially those secreting the IgG isotype, accumulate in the inflamed joints of RA patients.
10447928 Interleukin-8, interleukin-10, intercellular adhesion molecule-1 and vascular cell adhesio 1999 Aug The aim of this work was to determine differences in pro- and anti-inflammatory cytokine and adhesion molecule expression in synovial tissue from patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Synovial tissue samples were obtained from patients with RA and OA, and from healthy individuals. The expression of mRNA of interleukin (IL)-1beta, IL-4, IL-6, IL-8, IL-10, IL-13, tumour necrosis factor-alpha (TNF-alpha) and transforming growth-factor-beta1 (TGF-beta1) was evaluated by the polymerase chain reaction (PCR). In addition, IL-8 and IL-10 transcripts were measured by quantitative PCR. The expression of IL-8 and IL-10 proteins was determined by immunoperoxidase staining. To evaluate the inflammatory stage of synovial tissue, vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) protein expression was also determined. RA patients were found to display higher levels of adhesion molecules than patients with OA. PCR analysis showed a similar profile of cytokine transcripts between the OA and RA groups. Gene expression of IL-4 and IL-13 in synovium was undetectable. In contrast, IL-1beta, IL-6, IL-8, IL-10, TNF-alpha and TGF-beta1 transcripts were expressed by both groups. Increased levels of IL-8 and IL-10 transcripts and their proteins were observed in synovium from RA patients when compared to patients with OA and healthy controls. Thus, our data show that IL-8, IL-10, ICAM-1 and VCAM-1 expression levels are higher in synovial tissue from patients with RA than in similar tissue from patients with OA.
9861513 Usage analysis of a primary care medical resource on the Internet. 1998 Sep Physicians and patients need convenient access to quality medical information. This study's goal was to place a medical resource on the World-Wide Web (WWW), allow access to it through a simple to use interface, and analyze the usage of such a resource. The Family Practice Handbook (TFPH) was digitized and placed onto the WWW. Usage data was obtained from June 1995-June 1996. 118,804 individuals accessed TFPH viewing 409,711 pages of information. A broad spectrum of topics was accessed. TFPH proved to be an extremely popular resource, servicing the broad information needs of an international audience. These preliminary findings suggest the future promise of Internet medical resources.
10340640 Clinical usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase activi 1999 This study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant fluoride-sensitive acid phosphatase (TrFsACP) activity using 2,6-dichloro-4-acetylphenyl phosphate as substrate at pH 6.2 in metabolic bone diseases. The mean Z-scores of TrFsACP activity in patients on hemodialysis were higher than in healthy subjects (male: 2.04+/-1.98, n = 49, P < .05; female: 1.49+/-2.43, n = 39, P < .05) and increased with duration of hemodialysis (r = .516, P < .01). Bone alkaline phosphatase also was found to be significantly higher in hemodialysis patients (male: 0.93+/-1.49, P < .05; female: 1.66+/-2.42, P < .05) compared with normal subjects: but had lower correlation with duration of hemodialysis than TrFsACP (r = .277, P < .05). Ulcerative colitis (1.37+/-2.21, n = 15) in males showed a significantly higher Z-score of TrFsACP compared with control subjects (P < .05). The relationship of TrFsACP activity and ultrasound findings (stiffness; speed of sound [SOS]; broadband ultra sound attenuation [BUA]) in healthy women aged 30-75 years (n = 95) were inversely and significantly correlated with stiffness (r = -.465, P < .01 ), SOS (r = -.484, P < .01), and BUA (r = -.366, P < .01), but were age dependent. TrFsACP activity significantly correlated with stiffness (r = -.521, P < .05) and SOS (r = -.527, P < .05) only in the age group of 46-55 years. BUA (r = -.313, P > .05) did not correlate significantly in any subject in the present study. We conclude that serum TrFsACP activity is useful in the diagnosis and monitoring of bone turnover.
9228910 Clinical trials of interactive computerized patient education: implications for family pra 1997 Jul A systematic review of randomized clinical trials was conducted to evaluate the acceptability and usefulness of computerized patient education interventions. The Columbia Registry, MEDLINE, Health, BIOSIS, and CINAHL bibliographic databases were searched. Selection was based on the following criteria: (1) randomized controlled clinical trials, (2) educational patient-computer interaction, and (3) effect measured on the process or outcome of care. Twenty-two studies met the selection criteria. Of these, 13 (59%) used instructional programs for educational intervention. Five studies (22.7%) tested information support networks, and four (18%) evaluated systems for health assessment and history-taking. The most frequently targeted clinical application area was diabetes mellitus (n = 7). All studies, except one on the treatment of alcoholism, reported positive results for interactive educational intervention. All diabetes education studies, in particular, reported decreased blood glucose levels among patients exposed to this intervention. Computerized educational interventions can lead to improved health status in several major areas of care, and appear not to be a substitute for, but a valuable supplement to, face-to-face time with physicians.
9144766 Interleukin-6: structure-function relationships. 1997 May Interleukin-6 (IL-6) is a multifunctional cytokine that plays a central role in host defense due to its wide range of immune and hematopoietic activities and its potent ability to induce the acute phase response. Overexpression of IL-6 has been implicated in the pathology of a number of diseases including multiple myeloma, rheumatoid arthritis, Castleman's disease, psoriasis, and post-menopausal osteoporosis. Hence, selective antagonists of IL-6 action may offer therapeutic benefits. IL-6 is a member of the family of cytokines that includes interleukin-11, leukemia inhibitory factor, oncostatin M, cardiotrophin-1, and ciliary neurotrophic factor. Like the other members of this family, IL-6 induces growth or differentiation via a receptor-system that involves a specific receptor and the use of a shared signaling subunit, gp130. Identification of the regions of IL-6 that are involved in the interactions with the IL-6 receptor, and gp130 is an important first step in the rational manipulation of the effects of this cytokine for therapeutic benefit. In this review, we focus on the sites on IL-6 which interact with its low-affinity specific receptor, the IL-6 receptor, and the high-affinity converter gp130. A tentative model for the IL-6 hexameric receptor ligand complex is presented and discussed with respect to the mechanism of action of the other members of the IL-6 family of cytokines.
9717979 Differential use of immunoglobulin light chain genes and B lymphocyte expansion at sites o 1998 Aug The presence of germinal centre-like structures and clonotypic expansion of lymphocytes in RA synovia may indicate a site-specific immune response to local antigens, rather than passively entrapped immune cells, that sustains synovial inflammation. In this study we compare the nature of immunoglobulin light chain variable region gene use in the synovium of RA patients with peripheral B cells to determine the nature of the synovial immune response. Using Vlambda and Vkappa gene fingerprinting, which relies on differences in CDR3 length, we demonstrate differences in the pattern of Vlambda and Vkappa use and clonotypic expansion of B cells between the synovium and peripheral blood of RA patients. Further, we show that some synovial rearrangements with long CDR3 are selectively expanded. These longer than usual CDR3 were generated by a number of mechanisms including N-additions. However, the observed differences were not uniform in different patients. These observations suggest that local synovial antigens drive significant numbers of T and B lymphocytes selected from an existing repertoire shaped by genetic and environmental factors. Further, the data argue against passive retention of most B cells in the synovium of RA patients.
11439155 Switch in chemokine receptor phenotype on memory T cells without a change in the cytokine 2001 Jul Th1 and Th2 cells as defined by their cytokine profile are associated with the expression of the chemokine receptors CCR5 and CCR3, respectively. In committed human memory Th1 cells the cytokine profile is irreversibly expressed. However, it is not known if the chemokine receptor phenotypes of Th1 and Th2 cells are permanently associated to the cytokine profile or if it can be changed. To analyze the possibility of inducing a switch in chemokine receptor phenotype on memory Th cells we used differentiated memory Th cells isolated from synovial tissue (ST) samples of patients with rheumatoid arthritis (RA). Freshly isolated T cells, T-cell lines and T-cell clones from these tissues were manipulated with Th1 (interleukin (IL)-12 + anti IL-4) or Th2 (IL-4 + anti IL-12) inducing conditions. The surface expression of CCR5 and CCR3 was analyzed by flowcytometry and interferon (IFN)-gamma and IL-4 production by ELISA. A Th1-inducing cytokine environment increased the expression of CCR5 in Th1 cells and induced the expression of CCR5 in Th2 cells as compared to culture condition with only IL-2. Induction of CCR5 expression on Th2 clones was associated with secretion of some IFN-gamma. Moreover, the Th2-associated chemokine receptor CCR3 could be expressed on both Th1-dominant cell lines, and clones of Th1 and Th0 type after culture conditions with IL-4. This expression of CCR3 was associated with a reduced IFN-gamma production, but no IL-4 production could be induced. The IL-4-treated Th1 clones had a reduced migratory capacity against chemokines produced by ST cells compared to nonmanipulated T-cell clones. In contrast, the same IL-12-treated Th1 clones showed an increased migratory potential. Induction of the Th2-associated marker CCR3 on memory Th1 cells demonstrates that a change in chemokine receptor phenotype related to the Th2 type can be induced on terminally differentiated Th1 cells, without a change in the cytokine profile.
9649197 Abnormal T cell responses to bacterial superantigens in Behçet's disease (BD). 1998 May This study examines the nature of T cell hypersensitivity in BD. Highly purified T cells from 32 BD patients, from 29 rheumatoid arthritis (RA) patients and from 14 healthy individuals were cultured with various concentrations of Staphylococcal enterotoxins (SE) B and C1 in the presence of monocytes for 5 days, after which the production of interferon-gamma (IFN-gamma) was assessed. High concentrations of SE (1 ng/ml) stimulated BD T cells as well as control T cells to produce comparably high amounts of IFN-gamma, whereas low concentrations of SE (1 pg/ml) stimulated BD T cells much more effectively than normal or RA T cells. The hypersensitivity of BD T cells to low concentrations of SEC1 was restored with RA monocytes instead of BD monocytes, whereas BD monocytes could not elicit the SEC1-induced IFN-gamma production of RA T cells. Moreover, there were no significant differences between BD T cells and RA T cells in monocyte-independent IFN-gamma production stimulated with low or high concentrations of immobilized anti-CD3, or in the monocyte-mediated enhancement of IFN-gamma production stimulated with a low concentration of immobilized anti-CD3. These results confirm that T cell hypersensitivity is not confined to certain specific antigens in BD. More importantly, the data strongly suggest that abnormalities in signal transduction triggered by perturbation of T cell receptors, but not in that induced by cross-linking of CD3 molecules nor in that delivered through costimulation molecules, play an important role in the pathogenesis of BD.
9596551 Diclofenac/misoprostol: the European clinical experience. 1998 May OBJECTIVE: The fixed combination of diclofenac sodium and misoprostol (Arthrotec) is the only nonsteroidal antiinflammatory drug (NSAID) that contains a gastroprotective component and is available in 2 formulations:(1) an enteric coated core of diclofenac sodium 50 mg surrounded by a mantle of misoprostol 200 microg, and (2) a 75 mg enteric coated diclofenac core also surrounded by a 200 microg mantle of misoprostol. This article reviews the European clinical experience with both formulations in patients with arthritis. METHODS: Three randomized, blinded, multicenter studies, including one in general practice, evaluated the efficacy of combination diclofenac/misoprostol versus diclofenac or ibuprofen in a total of 1824 patients with rheumatoid arthritis (RA) or osteoarthritis (OA). Four additional studies assessed antiarthritic efficacy and employed endoscopy to compare the gastroduodenal safety of combined diclofenac50/misoprostol with that of diclofenac, naproxen, piroxicam, or indomethacin in 1459 patients with RA, OA, or ankylosing spondylitis. The gastroduodenal safety and antiarthritic efficacy of diclofenac75/misoprostol was compared with that of diclofenac in one endoscopy study involving 514 patients with RA or OA. RESULTS: The efficacy and safety data obtained from these European clinical trials show that both formulations diclofenac50/misoprostol and diclofenac75/misoprostol are effective antiinflammatory drugs, with clinical efficacy equivalent to that of diclofenac. Diclofenac50/misoprostol is at least as effective as naproxen, piroxicam, indomethacin, and ibuprofen. Both formulations of the combination were associated with significantly fewer gastroduodenal ulcers compared with diclofenac. In separate studies, the tolerability of diclofenac50/misoprostol (as determined by withdrawal rates) was shown to be equivalent to that of diclofenac, naproxen, piroxicam, and ibuprofen, and the tolerability of diclofenac75/misoprostol was shown to be equivalent to that of diclofenac. The diclofenac50/misoprostol was associated with fewer decreases in hemoglobin concentration compared with diclofenac in the general practice study as well as in hospital patients. CONCLUSION: Diclofenac50/misoprostol and diclofenac75/misoprostol are effective in treating the signs and symptoms of RA and OA and are well tolerated by the majority of patients. Both of these formulations achieve a significant reduction in the incidence of both gastric and duodenal ulcers compared with other NSAID.
9493987 Granuloma annulare, nodular type--a subcutaneous pseudorheumatoid lesion in children. 1997 Dec Five cases of patients aged between 2 years 8 months and 5 years 6 months with subcutaneous nodular granuloma annulare are reported. Histologically the lesions resembled rheumatoid nodules, consisting of acellular central areas surrounded by palisading histiocytes. Complete or partial excisions were done for diagnosis. Initially the granulomata were not associated with any symptoms of systemic illness, but one patient with IgG deficiency developed subsequent polyarthritis. Antistreptolysin O, antinuclear antibodies and latex fixation test for rheumatoid arthritis were negative except for one patient with additional erythema nodosum and elevated antistreptolysin level. In the other patients the laboratory data were uncharacteristic. The clinical course may be characterized by spontaneous regression and frequent recurrence. In asymptomatic patients further treatment is not necessary. Patients with progressive disease or elevated inflammatory activity were treated with nonsteroidal antirheumatics. The development of subsequent rheumatoid disease in primarily asymptomatic patients is unlikely, but we recommend further observation by an experienced pediatrician.
9717978 Substance P enhances cytokine-induced vascular cell adhesion molecule-1 (VCAM-1) expressio 1998 Aug Rheumatoid arthritis (RA) is an autoimmune disease characterized by inflammation of the synovial membrane of multiple joints. This inflammatory microenvironment allows fibroblast-like synoviocytes (FLS) to express or enhance several adhesion or costimulatory molecules. This phenotypic shift, under proinflammatory cytokines, seems to be related to functional consequences for antigen presentation to T cells. The sensory neuropeptide substance P (SP), present at high levels, is able to act on FLS proliferation and enzyme secretion. These data led us to investigate whether SP could also provoke a phenotypic change of FLS. Using flow cytometry and a three-step cellular ELISA method, we determined whether SP has an influence on the expression of MHC class II, intercellular adhesion molecule-1 (ICAM-1), VCAM-1, LFA-3, CD40, B7.1 or B7.2 molecules on RA FLS incubated with interferon-gamma (IFN-gamma) or IL-1beta or tumour necrosis factor-alpha (TNF-alpha) with or without SP. Our results indicate that SP potentiates the effect of proinflammatory cytokines on the expression of VCAM-1 on RA FLS. We verified the presence of specific SP (NK1) receptor mRNA. Using reverse transcription-polymerase chain reaction, we showed that RA FLS of patients express NK1 receptor mRNA. These results suggest that SP increase of cytokine-induced VCAM-1 expression acts via this specific SP receptor. Thus, during chronic inflammation RA FLS are at the interface between the immune and the nervous systems.
10094932 Decreased expression and activity of G-protein-coupled receptor kinases in peripheral bloo 1999 Apr Beta2-Adrenergic and chemokine receptor antagonists delay the onset and reduce the severity of joint injury in rheumatoid arthritis. beta2-Adrenergic and chemokine receptors belong to the G-protein-coupled receptor family whose responsiveness is turned off by the G-protein-coupled receptor kinase family (GRK-1 to 6). GRKs phosphorylate receptors in an agonist-dependent manner resulting in receptor/G-protein uncoupling via subsequent binding of arrestin proteins. We assessed the activity of GRKs in lymphocytes of rheumatoid arthritis (RA) patients by rhodopsin phosphorylation. We found a significant decrease in GRK activity in RA subjects that is mirrored by a decrease in GRK-2 protein expression. Moreover, GRK-6 protein expression is reduced in RA patients whereas GRK-5 protein levels were unchanged. In search of an underlying mechanism, we demonstrated that proinflammatory cytokines induce a decrease in GRK-2 protein levels in leukocytes from healthy donors. Since proinflammatory cytokines are abundantly expressed in RA, it may provide an explanation for the decrease in GRK-2 expression and activity in patients. No changes in beta2-adrenergic receptor number and Kd were detected. However, RA patients showed a significantly increased cAMP production and inhibition of TNF-alpha production by beta2-adrenergic stimulation, suggesting that reduced GRK activity is associated with increased sensitivity to beta2-adrenergic activation.
10388281 [LGL syndrome can imitate Felty's syndrome. The diagnosis can be established by a simple t 1999 May 26 The article consists in a discussion of neutropenia caused by large granular lymphocytes (LGLs), illustrated by a review of the literature and case reports of five patients with LGL syndrome and one patient whose clinical characteristics were more consistent with classic Felty's syndrome. Recent years have witnessed advances in our knowledge of clonal expansions of suppressor-type T-cells and their capacity to induce neutropenia. The phenotypes of such cells are CD3+, CD8+ and CD57+. The syndrome is often seen in patients with rheumatoid arthritis, and if they also manifest splenomegaly it may be confused with Felty's syndrome. Appropriate evaluation and treatment of the condition are also discussed, and an attempt made to clarify the confusing terminology.