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ID PMID Title PublicationDate abstract
11710548 Borage oil reduction of rheumatoid arthritis activity may be mediated by increased cAMP th 2001 Nov Recent double blind studies have shown some benefit of borage oil in treatment of rheumatoid arthritis. Tumor necrosis factor-alpha has been shown to be a central mediator of inflammatory and joint destructive processes in rheumatoid arthritis. In this paper, evidence from published research is reviewed that indicates gamma linolenic acid component of borage oil increases prostaglandin E levels that increase cAMP levels that in turn suppress tumor necrosis factor-alpha synthesis. If this biochemical path of borage oil is correct then (1) concomitant non-steroidal anti-inflammatory drug use would tend to undermine borage oil effects, and (2) borage oil would be contraindicated in pregnancy given the teratogenic and labor inducing effects of prostaglandin E agonists.
9592864 Pathological significance of elevated soluble CD14 production in rheumatoid arthritis: in 1998 In order to establish what contributes to elevated levels of soluble CD14 (sCD14) in rheumatoid arthritis (RA) plasma, levels of sCD14 were compared in RA-paired plasma and synovial fluids and, further, in the culture supernatants of monocyte-rich fractions from patients with RA and healthy donors, and macrophage-rich fractions from RA synovial tissues. The results showed elevated sCD14 in RA synovial fluid in 9 of 16 paired samples and in RA macrophage-rich fractions, suggesting that elevated sCD14 in RA plasma might be due to the sCD14 production by RA synovial macrophages. From the molecular analysis of elevated sCD14, the proteolytic cleavage of membranous CD14 (mCD14) was important in accelerated sCD14 production. Lipopolysaccharides (LPS) at low concentrations and sCD14 increased the ICAM-1 expression on RA synovial fibroblasts. This result implies that in vivo RA synovial fibroblasts may be sensitive to LPS in the presence of sCD14 and LPS-binding protein (LBP).
9458210 Distribution of HLA-DRB1 alleles of patients with polymyalgia rheumatica and giant cell ar 1998 Jan OBJECTIVE: To evaluate HLA-DRB1 associations in polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) compared to rheumatoid arthritis (RA). METHODS: One hundred twenty-one patients were included and oligotyped: 79 with PMR alone and 42 with GCA (14 also had PMR). We also genotyped 1609 healthy controls and 433 patients with RA. Statistical analysis included Fisher's exact test and calculation of the odds ratio (95% CI). RESULTS: Compared to controls, the DRB1*04 phenotype was increased in PMR (39.2%; OR = 2.4, p = 0.0005) and GCA (45.2%; OR = 3.1, p = 0.0005). This association was weaker than in RA (p = 0.01). DRB1*07 was more frequent in GCA (31.0%) than in PMR (13.4%; p = 0.03), but the difference was not significant in comparison to controls. The distribution of DRB1*04 subtypes was similar in PMR and GCA, but different from RA and controls. However, the frequency of 0402 and 0403 subtypes could not be distinguished from that in patients with RA. Double occurrence of RA associated alleles was less frequent in PMR and GCA (9.9%; p = 0.005) than in patients with RA (20.8%). There was no significant relationship between markers of disease activity/severity and HLA-DRB1 genes in PMR or GCA. CONCLUSION: PMR and GCA were associated with HLA-DRB1*04, but more weakly than RA. Nevertheless, these data suggest that HLA-DRB1* genes are closely related to susceptibility in PMR, GCA, and RA and do not support the hypothesis of a different linkage to the 3rd hypervariable region of DRB1 alleles. By contrast with RA, HLA-DRB1* genes do not appear to be indicators of disease severity in PMR and GCA.
10496313 Synovial PMN show a coordinated up-regulation of CD66 molecules. 1999 Sep Changes in the expression of various activation-dependent surface markers have been reported for polymorphonuclear neutrophils (PMN) isolated from synovial fluid of patients with inflammatory joint diseases. We extend these findings to the expression of CD66 molecules and several other surface markers. Three members of the CD66 family, namely CD66a, CD66b, and CD66c, showed an up to fourfold up-regulation on synovial fluid PMN compared with peripheral blood PMN (PBG) of the same patients; CD59 was increased twofold, the expression of CD16 did not change, whereas CD62L was reduced by more than 50% on synovial fluid PMN. It is interesting that CD66a, CD66b, and CD66c showed a coordinated expression on PBG of patients and controls and a coordinated up-regulation on synovial neutrophils. In contrast, after in vitro stimulation of peripheral blood PMN with phorbol myristate acetate, CD66c was much less up-regulated compared with CD66a and CD66b. All samples of synovial fluid PMN exhibited an additional increase in the expression of CD66a, CD66b, and CD66c when stimulated with phorbol myristate acetate in vitro. Prostaglandins are known to inhibit various responses of neutrophils to inflammatory stimuli. We could show that prostaglandins inhibit N-formyl-methionyl-leucyl-phenylalanine-induced up-regulation of CD66 on peripheral blood PMN in a concentration-dependent manner.
10545483 Gamma-glutamyl transpeptidase is up-regulated on memory T lymphocytes. 1999 Nov The ectoenzyme gamma-glutamyl transpeptidase (GGT) hydrolyzes glutathione (GSH), is required for the maintenance of normal intracellular GSH levels and modifies the activity of GSH-containing adducts. Previous data suggested that this enzyme was present on mitogen-activated T lymphocytes. However, the level of GGT protein expression on human mononuclear cell subsets has not been determined. A novel mAb to human GGT, 3A8, was developed. 3A8 was used to show that the expression of GGT is, in fact, highest on resting T cells that express markers of the memory phenotype, specifically CD45RO and decreased expression of CD45RB. The peripheral blood of patients with rheumatoid arthritis was found to have expanded numbers of T cells expressing levels of GGT up to 10-fold higher than controls. In addition, the CD4(+) T cell subset with the capacity to migrate across a human endothelial cell monolayer expresses high GGT levels. GGT expression was up-regulated on peripheral blood T cells following activation in vitro by either superantigen, phorbol ester, or IL-15, a stimulatory cytokine synthesized in rheumatoid synovium. Resting peripheral blood T cells that express GGT have higher levels of intracellular thiols than those that do not. These observations suggest that GGT may play an important role in the regulation of lymphocytes that are at a particular developmental stage.
11454644 Tumour necrosis factor microsatellites and HLA-DRB1*, HLA-DQA1*, and HLA-DQB1* alleles in 2001 Aug OBJECTIVE: To study the association between rheumatoid arthritis (RA) and HLA and tumour necrosis factor (TNF) polymorphism in Peruvian mestizo patients in comparison with ethnically similar controls. METHODS: Seventy nine patients with RA and 65 ethnically matched healthy controls were genotyped for HLA-DRB1, HLA-DQA1, HLA-DQB1, and TNFalpha and TNFbeta alleles using PCR amplification. Clinical severity was assessed as mild, moderate, or severe in 35 of the patients. RESULTS: TNFalpha6 showed the strongest association with disease susceptibility. The TNFalpha6 allele was more common in patients than in controls (p<0.0076) and the proportion of patients with at least one copy of this allele was greater (p<0.015, relative risk 2.35). Among the HLA-DRB1* alleles with the shared epitope sequence, only the DRB1*1402 allele was significantly increased in patients compared with controls (p<0.0311), as was the proportion of patients with at least one copy of this allele (p<0.0232, relative risk 2.74). In contrast, the overall frequency of alleles with the shared epitope was not different in patients and controls. The haplotype HLA-DRB1*1402-DQB1*0301-DQA1*0401 was significantly more common in patients. TNFalpha6 was more common in patients whether or not they had this haplotype. None of the 11 patients lacking the TNFalpha6 allele had severe disease. CONCLUSIONS: This study shows for the first time that TNF gene polymorphism is associated with susceptibility to RA in a non-white population. TNFalpha6 and HLA-DRB1*1402 independently conferred significantly increased risk in Peruvian mestizo patients.
9227327 Neutrophils from the synovial fluid of patients with rheumatoid arthritis express the high 1997 Jun Neutrophils isolated from the synovial fluid of 16/24 patients with rheumatoid arthritis expressed Fc gamma RI (CD64), the high-affinity receptor for monomeric immunoglobulin G (IgG), on their cell surface. Receptor expression ranged from 17% to 168% of the level of expression obtained after incubation of control blood neutrophils with 100 U/ml interferon-gamma (IFN-gamma) for 24 hr in vitro. Similarly, mRNA for Fc gamma RI was detected in synovial fluid neutrophils from 12/15 patients and transcript levels ranged from 5% to 200% of the values obtained after treatment of blood neutrophils with IFN-gamma for 4 hr in vitro. No surface expression nor mRNA were detected in freshly isolated blood neutrophils from either patients or from healthy controls. Addition of cell-free synovial fluid to control blood neutrophils induced both mRNA and surface expression of Fc gamma RI to levels that were comparable to those achieved after addition of IFN-gamma. Neither soluble nor insoluble immune complexes appeared to be involved in induction of Fc gamma RI expression in spite of the ability of these complexes to induce protein biosynthesis. Synovial fluid-induced expression of Fc gamma RI was partially blocked by incubation with neutralizing IFN-gamma antibodies, whilst neutralizing interleukin (IL)-6 antibodies had little effect. Levels of IFN-gamma measured within these synovial fluids ranged from 0 to 2.7 U/ml, well within the range known to induce neutrophil Fc gamma RI expression. These data thus indicate that gene expression in synovial fluid neutrophils is selectively activated as the cells enter the diseased joint. Furthermore, these data indicate that induced expression of Fc gamma RI may alter the ability of infiltrating neutrophils to respond to IgG-containing immune complexes present in these joints.
11890354 Oprelvekin. Genetics Institute. 2001 Oct Genetics Institute has developed and launched oprelvekin (rhIL-11; Neumega), a recombinant form of human IL-11. In November 1997, the FDA cleared oprelvekin for the prevention of severe thrombocytopenia and the reduction of the need for platelet transfusions following myelosuppressive chemotherapy in susceptible patients with non-myeloid malignancies 12703021. The product was launched at the end of 1997 [312556]. By December 1999, phase III trials for Crohn's disease (CD) were underway [363007]. Genetics Institute had commenced a 150-patient phase II trial for mild-to-moderate CD and mucositis and the company planned to file regulatory procedures for the indication of CD in 1999 [271210]. An oral formulation for this indication has been developed. Oprelvekin is also undergoing phase I clinical trials for colitis [396157], phase II clinical trials for rheumatoid arthritis [413835] and clinical trials for psoriasis [299644]. In March 1997, Wyeth-Ayerst became the licensee for Europe, Africa, Latin America and Asia (with the exception of Japan). Genetics Institute holds marketing rights for North America [239273]. In Japan, oprelvekin is being developed by Genetics Institute and Yamanouchi; phase III trials have commenced [295049] and were ongoing in May 2001 [411763]. In April 1996, analysts at Yamaichi estimated launch in 2001 and maximum annual sales of over yen 10 billion [215896]. In January 1998, Morgan Stanley Dean Witter predicted Yamanouchi's share of sales to be yen 1 billion in 2001, rising to yen 2 billion in 2002 [315458]. Sales of oprelvekin were US $34 million for Genetics institute in fiscal 2000 while, in July 2001, Credit Suisse First Boston estimated that this figure will be US $30 million and US $34 million in 2001 and 2002, respectively [416883].
10504381 Serum amyloid A, the major vertebrate acute-phase reactant. 1999 Oct The serum amyloid A (SAA) family comprises a number of differentially expressed apolipoproteins, acute-phase SAAs (A-SAAs) and constitutive SAAs (C-SAAs). A-SAAs are major acute-phase reactants, the in vivo concentrations of which increase by as much as 1000-fold during inflammation. A-SAA mRNAs or proteins have been identified in all vertebrates investigated to date and are highly conserved. In contrast, C-SAAs are induced minimally, if at all, during the acute-phase response and have only been found in human and mouse. Although the liver is the primary site of synthesis of both A-SAA and C-SAA, extrahepatic production has been reported for most family members in most of the mammalian species studied. In vitro, the dramatic induction of A-SAA mRNA in response to pro-inflammatory stimuli is due largely to the synergistic effects of cytokine signaling pathways, principally those of the interleukin-1 and interleukin-6 type cytokines. This induction can be enhanced by glucocorticoids. Studies of the A-SAA promoters in several mammalian species have identified a range of transcription factors that are variously involved in defining both cytokine responsiveness and cell specificity. These include NF-kappaB, C/EBP, YY1, AP-2, SAF and Sp1. A-SAA is also post-transcriptionally regulated. Although the precise role of A-SAA in host defense during inflammation has not been defined, many potential clinically important functions have been proposed for individual SAA family members. These include involvement in lipid metabolism/transport, induction of extracellular-matrix-degrading enzymes, and chemotactic recruitment of inflammatory cells to sites of inflammation. A-SAA is potentially involved in the pathogenesis of several chronic inflammatory diseases: it is the precursor of the amyloid A protein deposited in amyloid A amyloidosis, and it has also been implicated in the pathogenesis of atheroscelerosis and rheumatoid arthritis.
10441838 The effects of NSAID on the matrix of human articular cartilages. 1999 Jun The present paper presents data obtained over a 12 year period, on the matrix synthesis and turnover in some 650 arthritic and 180 non-arthritic (N) human cartilages using a standardised in vitro method. When the relative metabolic (synthetic/repair activity) of these human cartilages was compared, it was demonstrated that in osteoarthritis (OA) and rheumatoid arthritis (RA) cartilages synthetic activity was diminished by approximately 50% as compared with N cartilages. However, the turnover rate of matrix was not significantly different between Non-arthritic and OA, but was very substantially increased in RA cartilages compatible with the activity of inflammatory cells and proteolytic enzymes released from pannus. The action of 13 NSAIDs was compared in terms of their effect on cartilage GAG synthesis. 3 of these NSAIDs were also studied in terms of their effect on cartilage collagen synthesis. Consideration of the results in this study and from published material, led to the suggestion that NSAIDs may be divided into 3 categories in respect of their in vitro action on the extracellular matrix of human arthritic cartilages: 1. Those such as Aceclofenac, Tenidap and Tolmetin which can stimulate matrix synthesis 2. Those such as Piroxicam, Tiaprofenic Acid and Aspirin which appear to be without significant effect on matrix synthesis and, 3. Those like Naproxen, Ibuprofen, Indomethacin, Nimezulide which significantly inhibit matrix synthesis. It is suggested that the stimulatory action of group 1 NSAID is due to inhibition of locally produced IL1 and consequent expression of growth factor activity. Other NSAIDs may also inhibit IL1 synthesis or release, but probably do not have a beneficial effect on chondrocyte synthetic activity as they have toxic effects on cartilage metabolism. These experiments led to the suggestion that NSAIDs such as Aceclofenac would be appropriate for long-term treatment of arthritic conditions provided that one is prepared to extrapolate between in vitro experiments on human cartilage and what may be happening in vivo.
11564773 Bm1-Bm5 classification of peripheral blood B cells reveals circulating germinal center fou 2001 Oct 1 Analyses of B cells in the bone marrow and secondary lymphoid tissues have revealed a broad range of cell surface markers defining B cell subpopulations, but only a few of these have been used to analyze B cell subpopulations in peripheral blood (PB). We report here the delineation of circulating PB B cell subpopulations by staining for CD19, CD38, and IgD in combination with CD10, CD44, CD77, CD95, CD23, IgM, and the B cell memory marker CD27. The utility of this approach is shown by the demonstration of disturbances of circulating B cell subpopulations in patients with autoimmune disease. Five mature B cell (Bm) subpopulations were identified in normal PB that were comparable with the tonsillar Bm1, Bm2, early Bm5, Bm5 subpopulations and, surprisingly, to the germinal center (GC) founder cell subpopulation (Bm2' and Bm3delta-4delta), suggesting that some GC founder cells are circulating. No PB B cells resembled the Bm3 and Bm4 GC cells. Remarkably, some cells with the CD38-IgD+ phenotype, previously known as naive Bm1 cells, expressed CD27. The CD38-IgD+ subpopulation therefore includes both naive Bm1 cells and IgD+ memory B cells. This new classification of B cell developmental stages reveals disturbances in the proportions of B cell subpopulations in primary Sjögren's syndrome (pSS) patients compared with healthy donors and rheumatoid arthritis patients. Patients with pSS contained a significantly higher percentage of B cells in two activated stages, which might reflect a disturbance in B cell trafficking and/or alteration in B cell differentiation. These findings could be of diagnostic significance for pSS.
11454648 Prevalence of TTV DNA and GBV-C RNA in patients with systemic sclerosis, rheumatoid arthri 2001 Aug OBJECTIVE: To determine the prevalence of GB virus-C (GBV-C) RNA and TT virus (TTV) DNA in patients with systemic sclerosis (SSc), rheumatoid arthritis (RA), and osteoarthritis (OA) as well as to compare the autoantibody pattern in patients with SSc with and without evidence of viral infection. PATIENTS AND METHODS: The study included 168 patients (84 SSc, 41 RA, and 43 OA) diagnosed according to the American College of Rheumatology criteria and 122 volunteer blood donors. The presence of GBV-C RNA and TTV DNA in serum was assessed by nested reverse transcriptase-polymerase chain reaction (RT-PCR) and semi-nested PCR, respectively. Autoantibodies in patients with SSc were determined by enzyme linked immunosorbent assay (ELISA) and Hep-2 immunofluorescence. RESULTS: TTV-DNA was detected in 10/84 (12%) patients with SSc, 9/41 (22%) patients with RA, 3/43 (7%) patients with OA, and 16/122 (13%) blood donors. GBV-C RNA was present in 4/84 (5%) patients with SSc, 2/43 (5%) patients with OA, and 5/122 (4%) blood donors. No patient with RA was positive for GBV-C RNA. One patient with SSc and one patient with OA showed a double infection with GBV-C and TTV. 74/84 (88%) patients with SSc were positive for at least one autoantibody species tested: 18/84 (21%) showed anticentromeric autoantibodies, 55/84 (66%) a speckled (36/84 (43%) fine, 19/84 (23%) coarse), and 20/84 (24%) a homogeneous nuclear Hep-2 pattern, and 21/84 (25%) had antinucleolar autoantibodies. Anti-Scl-70 antibodies were found in 31/84 (37%) and anti-RNP antibodies in 5/84 (6%) patients with SSc. No differences in the autoantibody pattern in patients with SSc with or without viral infection could be detected. CONCLUSION: The prevalence of GBV-C RNA and TTV DNA in serum samples from patients with SSc, RA, and OA was low and comparable with that in blood donors. A continuing infection with TTV and or GBV-C was not associated with a significant change in the autoantibody pattern in patients with SSc. These data provide no evidence for an association between GBV-C and/or TTV infections and SSc and/or arthritis (RA and OA).
9775069 [RS3PE: a clinical diagnosis, a prognosis more simple than its name]. 1998 Aug INTRODUCTION: RS3PE syndrome (remittive symmetrical seronegative synovitis with pitting edema) was first described by MacCarthy in 1985. It is a rare type of seronegative polyarthritis occurring in the elderly. METHODS: Retrospective report of 13 cases (including eight male and five female patients; mean age 76.7 +/- 3.7 years) and search for previously reported cases, using the Medline database. RESULTS: Pitting edema was present at onset of disease in nine cases. Joint arthritis was bilateral, occurring in the wrist (13 cases), shoulder (six cases), elbow (six cases), knee (six cases), ankle (four cases), metacarpophalangeal (four cases) and hip (one case). Radiographies were normal. Mean erythrocyte sedimentation rate was 62 +/- 19 mm at the first hour and mean C-reactive protein level was 73 +/- 35 mg/L. Mild cholestasis was present in four of the seven patients for whom data were available. HLA B7 was present in five out of 12 cases (42%). Improvement was favorable, occurring over 7 months. Mean follow-up was 22.2 months. Fifty-nine other cases have been described in the literature. This syndrome, which affects the elderly, appears to be rare. Its clinical presentation is quite constant, with sudden onset, symmetrical polyarthritis and pitting edema. Its evolution, often long, is favorable. Rheumatoid arthritis and polymyalgia rheumatica are the main differential diagnoses. CONCLUSION: Due to its favorable outcome and the usefulness of a mild corticotherapy, this syndrome, though rare, should be diagnosed where necessary in elderly patients.
9416848 Ribozyme-based gene cleavage approach to chronic arthritis associated with human T cell le 1997 Dec OBJECTIVE: To develop gene therapy for patients with human T cell leukemia virus type I (HTLV-I)-associated arthropathy (HAAP), we investigated the effects of ribozyme-mediated cleavage of HTLV-I tax/rex messenger RNA (mRNA) on synovial overgrowth. METHODS: We introduced 2 hammerhead ribozymes targeted against HTLV-I tax/rex mRNA into synovial cells obtained from patients with HAAP and from patients with HTLV-I-negative rheumatoid arthritis (RA) and examined the ribozyme-mediated ablation of Tax expression. Using standard methods, we also determined the cells' ability to stop proliferating and to undergo apoptosis. RESULTS: The ribozymes successfully cleaved tax/rex mRNA in HAAP patient synoviocytes. Both tax mRNA expression and Tax protein synthesis were inhibited significantly, resulting in inhibition of synovial cell growth and induction of apoptosis. In contrast, synovial cells from RA patients were not affected. CONCLUSION: In vitro results suggest that ribozyme-mediated gene therapy can inhibit the growth of HTLV-I-infected synovial cells, which is maintained by Tax protein, in HTLV-I-related diseases including HAAP.
10404054 Increased expression of down-regulatory CTLA-4 molecule on T lymphocytes from rheumatoid s 1999 Jul Since the CTLA-4 molecule expressed on activated T lymphocytes has recently been suggested to be an important negative regulator in autoimmune diseases, this study was undertaken to investigate the expression and function of CTLA-4 on synovial T cells from patients with rheumatoid arthritis. CTLA-4-expressing T cells were detected using a dual fluorescence flow cytometric method. Only a small percentage of peripheral blood T cells from patients with rheumatoid arthritis had detectable surface CTLA-4 expression (mean +/- SD, 1. 89 +/- 1.92%). However, the levels of CTLA-4-positive T cells was increased significantly in rheumatoid synovial fluids (5.44 +/- 4. 96%) and synovial membranes (28.76 +/- 14.30%). To explore the role of CTLA-4 molecule in the inflammation of rheumatoid joints, CTLA-4 was blocked with anti-CTLA-4 antibody to assess its effects on the production of tumour necrosis factor alpha and interleukin 1beta in synovial fluid mononuclear cell culture. The addition of anti-CTLA-4 antibody enhanced the production of tumour necrosis factor alpha and interleukin 1beta in a dose-dependent manner. The data suggest that the expression of CTLA-4 plays a down-regulatory role in rheumatoid articular inflammation. We thus concluded that CTLA-4 was up-regulated on synovial T cells from patients with RA, and the increased CTLA-4 expression might exert a down-regulation effect on tumour necrosis factor alpha and interleukin 1beta production.
10405519 Specific cyclooxygenase-2 (COX-2) inhibitors. 1999 Jun Nonsteroidal anti-inflammatory drugs (NSAIDs) are currently among the most widely prescribed drugs worldwide. Their therapeutic benefits and their side effects in the gastrointestinal tract and kidney, as well as in hemostasis, are of great importance in modern medicine. Within the past decade, new insights into how NSAIDs produce both their therapeutic benefits and their serious side effects have been discovered. It is now known that there are two froms of the cyclooxygenase (COX) enzyme that metabolize arachidonic acid into prostaglandins. Drugs that specifically inhibit the COX-2 enzyme were formulated and put into clinical trials during the past 5 years. These drugs are now available to treat patients in the United States. Specific COX-2 inhibitors offer the benefit of being able to treat the pain and inflammation of arthritis with potentially little risk of serious gastrointestinal injury.
9228120 Expression of vascular endothelial growth factor in synovial fibroblasts is induced by hyp 1997 Jul OBJECTIVE: To study the mechanism by which hypoxia and inflammatory cytokines mediate angiogenesis in the rheumatoid pannus through their effects on the fibroblast-like type B synoviocyte, the major cell type of normal synovia. METHODS: Fibroblasts were prepared from synovial tissue of healthy and diseased individuals, and cultured in the presence of various stimuli. The expression of vascular endothelial growth factor (VEGF) was assessed by ELISA and reverse transcription polymerase chain reaction. RESULTS: Unlike normal fibroblasts, synovial fibroblasts from rheumatoid arthritis (RA) and osteoarthritis constitutively secreted significant levels of VEGF, which is known to act directly on endothelial cells. VEGF secretion was further inducible by both hypoxia and interleukin 1beta (IL-1beta) and these increases were additive. In contrast, tumor necrosis factor alpha was unable to induce VEGF expression. CONCLUSION: Under hypoxia or IL-1 stimulation, conditions common to the inflamed synovium, type B synoviocytes secrete increased levels of VEGF, which is likely to act on nearby endothelia, promoting angiogenesis. The constitutive expression of VEGF in rheumatoid synovial fibroblasts may reflect an altered phenotype involved in the pathology of RA.
11805414 Is reduced quality of life in men with lower urinary tract symptoms due to concomitant dis 2001 Dec OBJECTIVES: To establish the effect of lower urinary tract symptoms (LUTS) on general health in an unselected male population in Finland using a reduction in general health as outcome. A further special focus was on the question of whether the effects can be accounted for by other concomitant health problems or solely by LUTS. METHODS: A population-based questionnaire study among 50-, 60- and 70-year-old men was conducted. The subjects were divided into 5 different groups according to the severity of the LUTS. Odds ratios (ORs) of reduced general health with 95% confidence intervals (CIs) were counted for every group and the effects of age and diseases were controlled. The population etiologic fraction was determined. RESULTS: The crude relative risks of reduced general health increased with any of the LUTS compared to men not having LUTS. Adjustment for age and concomitant diseases reduced the ORs, but the associations remained similar. Relatively the effect of adjustment was greatest in men with several and serious symptoms, i.e. in men with the highest scores (OR 11.1 vs. 6.9). CONCLUSIONS: LUTS and perceived general health are strongly correlated. About half of the association was accounted for by age and concomitant diseases, but the other half of the crude effect would appear to be independent of these factors. Severe LUTS severely affects the general health.
11184349 Rural beneficiaries with chronic conditions: does prevalence pose a risk to Medicare manag 2000 Summer One of several possible barriers to the growth of Medicare managed care in rural areas is the fear of adverse selection (i.e., the perception that rural beneficiaries are less healthy and have pent-up demand for services). Using 1993 Medicare Current Beneficiary Survey data, we conclude that specific chronic conditions common among the elderly are not more prevalent among rural than urban beneficiaries. Medicare reimbursements for beneficiaries with chronic conditions are generally lower in rural counties. However, the difference between actual Medicare reimbursements and projected capitated payments to managed care organizations is similar in magnitude for rural and urban beneficiaries with these conditions.
9165996 Absence of peripheral blood T cell responses to "shared epitope' containing peptides in re 1997 Apr OBJECTIVES: To determine if peptides containing the 'shared epitope' sequence, QKRAA, from either endogenous, HLA-DR beta 1 (0401), or exogenous, Escherichia coli dnaJ, sources activate T cells in recent onset rheumatoid arthritis (RA). METHODS: Peripheral blood mononuclear cell (PBMC) proliferative and whole blood cytokine responses to shared epitope containing peptides from DR beta 1 (0401) and E coli dnaJ, to control peptides from DR beta 1 (0402) and hsp40 and to the recall antigen, tetanus toxoid, were tested in 20 untreated, recent onset RA subjects, 20 HLA, age, and sex matched healthy controls and 18 other subjects with inflammatory arthritis. PBMC proliferative responses to a second E coli dnaJ peptide (with the shared epitope at the N-terminus) and two peptides from type II collagen with high affinity for DR4(0401) were tested in a further 16 recent onset RA and 17 control subjects. RESULTS: PBMC proliferation and whole blood interferon gamma or interleukin 10 production in response to the shared epitope containing and control peptides were not different between the disease and control groups. On the other hand, compared with controls, RA subjects had significantly higher proliferation to a collagen II (aa 1307-1319) peptide, but significantly lower proliferation and interferon gamma production to tetanus toxoid. CONCLUSION: Recent onset RA subjects had no demonstrable increase in peripheral blood T cell reactivity to shared epitope containing peptides. However, a proportion had increased T cell reactivity to a peptide of similar length from a candidate RA autoantigen, collagen type II. Their impaired responses to tetanus are in keeping with evidence for general T cell hyporesponsiveness in RA.