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ID PMID Title PublicationDate abstract
7657832 Apoptosis in rheumatoid arthritis synovium. 1995 Sep RA synovial tissue (ST) was studied to determine if and where apoptosis occurs in situ. Genomic DNA was extracted from 5 RA and 1 osteoarthritis ST samples. Agarose gel electrophoresis demonstrated DNA ladders characteristic for apoptosis from each tissue. In situ and labeling (ISEL) was used to identify DNA strand breaks consistent with apoptosis in frozen sections. 12 RA and 4 osteoarthritis ST were studied by ISEL and all were positive, but only 2 of 4 normal tissues were positive. The primary location of apopotic cells was the synovial lining. Some sublining cells were also positive, but lymphoid aggregate staining was conspicuously absent. Immunohistochemistry and ISEL were combined and showed that the lining cells with DNA strand breaks were mainly macrophages, although some fibroblastlike cells were also labeled. Sublining cells with fragmented DNA included macrophages and fibroblasts, but T cells in lymphoid aggregates, which expressed large amounts of bcl-2, were spared. DNA strand breaks in cultured fibroblastlike synoviocytes was assessed using ISEL. Apoptosis could be induced by actinomycin D, anti-fas antibody, IL-1, and TNF-alpha but not by IFN-gamma. Fas expression was also detected on fibroblast-like synoviocytes using flow cytometry. Therefore, DNA strand breaks occur in synovium of patients with arthritis. Cytokines regulate this process, and the cytokine profile in RA (high IL-1/TNF; low IFN-gamma) along with local oxidant injury might favor induction of apoptosis.
8332151 Maternal-fetal disparity in HLA class II alloantigens and the pregnancy-induced ameliorati 1993 Aug 12 BACKGROUND: Rheumatoid arthritis frequently remits during pregnancy, for unknown reasons. Since an immune response to paternally inherited fetal HLA can occur during normal pregnancy and since rheumatoid arthritis is an autoimmune disorder with a known HLA class II antigen association, we tested the hypothesis that maternal-fetal disparity in HLA alloantigens might be associated with the pregnancy-induced remission of rheumatoid arthritis. METHODS: We studied 57 pregnancies of 41 women with rheumatoid arthritis, 18 prospectively and 39 retrospectively. Serologic and DNA techniques were used to study HLA class I and II antigens. For newborns, typing was performed from cord-blood samples obtained at delivery. For four young children, typing was performed from DNA extracted from hair samples. RESULTS: We found significantly more maternal-fetal disparity in HLA-DR and DQ antigens in pregnancies characterized by the remission or improvement of rheumatoid arthritis than in pregnancies characterized by active disease. Further studies using DNA-typing techniques to define allelic variants of HLA-DR and DQ antigens confirmed this observation. Maternal-fetal disparity in alleles of HLA- DRB1, DQA, and DQB occurred in 26 of 34 pregnancies characterized by remission or improvement (76 percent), as compared with 3 of 12 pregnancies characterized by active arthritis (25 percent) (odds ratio, 9.7; P = 0.003). The difference between the two groups was most marked for alleles of HLA-DQA. CONCLUSIONS: Amelioration of rheumatoid arthritis during pregnancy is associated with a disparity in HLA class II antigens between mother and fetus. These findings suggest that the maternal immune response to paternal HLA antigens may have a role in the pregnancy-induced remission of rheumatoid arthritis.
7702413 Electron spin resonance spectroscopic demonstration of the generation of reactive oxygen s 1995 Feb OBJECTIVE: To apply an electron spin resonance (ESR) spectroscopic technique as a means of determining the oxidising capacity of reactive oxygen species produced during hypoxia and reoxygenation of diseased human synovial tissue. METHODS: Twenty four specimens of fresh synovial tissue were obtained from patients undergoing primary total knee joint replacement and graded according to the degree of inflammation present. Tissue samples were subjected to an ex vivo hypoxia-reoxygenation cycle in the presence of the nitroso based spin trap, 3,5-dibromo-4-nitrosobenzene sulphonate. The degree of oxidation of the spin trap to a stable free radical was determined and followed with time. Control samples were subjected to hypoxia only. RESULTS: The results indicate that the oxidising capacity of reactive oxygen species produced by human synovial tissue varies with the degree of inflammation present. Only the more inflamed specimens, from both rheumatoid arthritis and osteoarthritis patients, demonstrated increased production of reactive oxygen species when subjected to a hypoxia-reoxygenation cycle. This change was reduced by both competitive and non-competitive inhibitors of the endothelial based enzyme xanthine oxidase. The relative concentration of reactive oxygen species generated by the synovial tissue samples correlated with the mean capillary density of the specimens. CONCLUSION: This study supports the hypothesis of movement induced hypoxicreperfusion injury of the chronically inflamed joint by demonstrating the generation of reactive oxygen species within inflamed human synovium following an ex vivo hypoxia-reoxygenation cycle. Evidence is presented that the microvascular endothelial based enzyme xanthine oxidase is the predominant source of ESR detectable oxidising species in inflamed synovial specimens exposed to hypoxia-reoxygenation.
7561064 Contribution of IL-1, CD14, and CD13 in the increased IL-6 production induced by in vitro 1995 Oct 1 Rheumatoid synovitis is characterized by an infiltration of mononuclear cells and by the proliferation of synoviocytes. Monocytes and synoviocytes are major producers of cytokines, growth factors, and enzymes that contribute to the rheumatoid arthritis (RA) process. Since they are in close contact in vivo, we engaged in an in vitro study of the functional consequences of their interactions. Coculture of unstimulated elutriated normal blood monocytes over RA synoviocytes resulted in a synergistic increase of the production of IL-6, granulocyte-macrophage colony-stimulating factor (GM-CSF), leukemia inhibitory factor (LIF), and IL-8, when compared with their respective production in culture alone. In contrast, cytokines such as IL-10, IL-1 beta, IL-1 alpha, and TNF-alpha could not be detected. The IL-6 production in coculture was further increased by the addition of IL-1 beta, GM-CSF, IFN-gamma, or TNF-alpha, but was inhibited by the addition of IL-10, IL-4, IL-13, or IL-1Ra, an effect reverted by the addition of IL-1 beta. Moreover, an inhibition was also observed with anti-CD14 mAb and newly raised mAbs directed against RA synoviocytes. Under reducing conditions, the mAb SY12 precipitated a 150-kDa surface membrane protein, identified as amino-peptidase N (CD13/AP-N). Collectively, these results indicate that 1) monocytes and synoviocytes interact with each other to produce proinflammatory cytokines, 2) pro- and antiinflammatory cytokines have opposite effects on IL-6 production, and 3) molecules such as IL-1, CD14, and CD13 are involved.
8675695 Paradoxical effects of a synthetic metalloproteinase inhibitor that blocks both p55 and p7 1996 Jun 15 We have previously hypothesized that the pro-inflammatory cytokine TNF alpha has a pivotal role in the pathogenesis of rheumatoid arthritis (RA). It mediates its effects by cross-linking surface p55 TNF receptors (TNF-R), which can be proteolytically cleaved to yield soluble fragments. Upon binding TNF alpha soluble TNF-R (sTNF-R) can inhibit its function. We investigated the enzymatic nature of the proteases involved in TNF-R cleavage, and found that this process is blocked by a synthetic inhibitor of matrix metallo-proteinase activity (MMP), BB-2275. Inhibition of TNF-R cleavage was observed in a number of different cell types, as detected by retention of surface bound TNF receptor and by less sTNF-R released into the cell supernatant. The augmentation of surface TNF-R expression was of biological relevance as TNF alpha-mediated necrosis of human KYM.1D4 rhabdosarcoma cells was enhanced approximately 15-fold in the presence of BB-2275. The addition of BB-2275 to rheumatoid synovial membrane cell cultures totally inhibited MMP activity and also significantly reduced the levels of soluble TNF alpha (P < 0.006), p55 sTNF-R (P < 0.006), and p75 sTNF-R (P < 0.004). Paradoxically, despite the reduction in soluble TNF alpha levels, the production of IL-1 beta, IL-6, and IL-8, cytokines whose production was previously demonstrated to be inhibited by the addition of neutralizing anti-TNF alpha antibody were not down-regulated by BB-2275. These results raise the interesting possibility that a close relationship exits between the enzyme(s) which process membrane-bound TNF alpha, and those involved in surface TNF-R cleavage. Furthermore our observations suggest that hydroxamate inhibitors of MMP activity which block TNF alpha secretion and TNF-R cleavage may not modulate down-stream effects of TNA alpha, and as such suggest that the precise specificity of these compounds will be highly relevant to their clinical efficacy in inflammatory diseases.
8205398 Interleukin-8 secretion and 15-lipoxygenase activity in rheumatoid arthritis: in vitro ant 1994 Jun We have examined the ability of interleukin-4 (IL-4), interleukin-10 (IL-10) and interleukin-1 receptor antagonist protein (IL-1ra) to regulate spontaneous interleukin-8 (IL-8) production in cultured SF mononuclear cells (SFMC) from RA. Furthermore, we examined whether IL-4, IL-10, or IL-1ra could influence the production of the arachidonic acid products leukotriene B4 (LTB4), 12-hydroxy-eicosatetraenoic acid (12-HETE) and 15-hydroxy-eicosatetraenoic acid (15-HETE). IL-4 induced a maximal suppression of 75% in the IL-8 secretion in SFMC from 10.0 ng/ml down to 2.5 ng/ml after 24 h and from 17.2 ng/ml to 4.2 ng/ml after 72 h of culture. IL-10 induced a 55% inhibition of the IL-8 secretion at 24 h and a 40% inhibition at 72 h. IL-1ra did not change the spontaneous IL-8 secretion from rheumatoid SFMC. We also examined, whether addition of IL-4, IL-10 or IL-1ra was able to modulate formation of the arachidonic acid products LTB4, 12-HETE and 15-HETE in cultured SF cells, stimulated with the calcium ionophore A23187. 15-HETE was not detected in untreated cultures, nor in IL-10 or IL-1ra treated cultures. IL-4, however, stimulated the formation of the anti-inflammatory mediator; 15-HETE (23 ng/10(6) cells). These results suggest that IL-4 or IL-10, could have beneficial anti-inflammatory effects in RA.
7556576 The distribution of TM-316-associated surface antigen on polymorphonuclear leucocytes: an 1995 Sep 29 It has been established that MoAb TM-316 recognizes an epitope on leucocytes and specifically inhibits the chemotactic behavior of leucocytes. In the present paper, the distribution of this epitope on the cell surface and in intracellular organelles was studied by immunoelectron microscopy. Leucocytes separated from the blood of healthy men and from synovial fluid from patients suffering from rheumatoid arthritis were used. They were fixed with a mixture containing paraformaldehyde, glutaraldehyde and picric acid. As the second antibody, goat anti-mouse IgM conjugated to 10 nm gold colloids was employed. In normal specimens, the epitope was found to some extent on the cytoplasmic membrane of neutrophilic leucocytes, but it was only sparsely distributed on eosinophilic and basophilic leucocytes. On activated neutrophilic leucocytes, obtained from the synovial fluid of rheumatoid arthritis patients, the immunolabeling was markedly increased. The number of sites where the epitope occurs on the surface of leucocytes is thus associated with the cell type, and also with the level of activation of the leucocytes. In order to investigate the processing of the antigen, the intracellular localization of the epitope in the neutrophilic leucocytes was also studied. The epitope recognized by TM-316 was also detected in/on the characteristic granules and Golgi stacks.
1532354 Low blood and synovial fluid levels of sulpho-conjugated steroids in rheumatoid arthritis. 1992 Jan Using radioimmunoassays (RIA) we measured the concentrations of prolactin, cortisol, dehydroepiandrosterone sulphate (DHEAS), pregnenolone sulphate (5-PS) and testosterone sulphate (TS) in peripheral blood and synovial fluid (SF) from 50 patients with arthritis of the knee associated with different diagnoses. These included RA (25 cases); and psoriasis, ankylosing spondylitis, reactive arthritis, post-traumatic arthritis, unspecified polyarthritis, polyarthritis and sacroilitis, and regional enteritis (25 cases). Fifty-six healthy subjects (age 19 to 60 years) were used as controls. No significant difference was found between the blood prolactin levels in patients and controls. The mean levels of cortisol, 5-PS, DHEAS and TS were significantly reduced in the patients with RA (mean 133 vs 286 nmol/l cortisol, 26 vs 80 nmol/l 5-PS, 930 vs 3290 nmol/l DHEAS and 25 vs 40 nmol/l TS; p less than 0.001 for cortisol, 5-PS and DHEAS, and p less than 0.05 for TS). The reduction was more marked in the DHEAS levels in patients with positive rheumatoid factor (RF) reactivity. Patients with diagnoses other than RA had normal levels of the various steroids except patients on steroid treatment, who also exhibited reduced levels. The 5 hormones measured in the SF were found in relatively high concentrations, parallelling those in the blood. The ratios (SF/blood) varied from 0.66 for 5-PS to 1.1 for cortisol, and the correlation coefficients between 0.66 for 5-PS and 0.94 for DHEAS (p less than 0.001). Low blood and SF levels of sulpho-conjugated steroids, particularly DHEAS, are a permanent disorder in patients with RA and positive RF reactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
7774103 Modified expression of c-Fos and c-Jun proteins and production of interleukin-1 beta in pa 1995 Jan OBJECTIVE: To examine the relationship between the expression of c-Fos and c-Jun proteins and the METHODS: The expression of c-Fos and c-Jun proteins and the production of IL-1 beta in the PBMC of 11 patients with active RA was determine by Western blots and ELISA techniques, respectively. RESULTS: The spontaneous expression of c-Fos protein and the production of IL-1 beta was higher in RA patients. Under LPS treatment, the PBMC of both RA patients and healthy subjects produced similar high levels of IL-1 beta without any significant changes in the expression of c-Fos and c-Jun proteins. By contrast, PMA-induced production of IL-1 beta was impaired in RA patients and was preceded by the disregulated expression of c-Fos and c-Jun proteins when compared with healthy donors. CONCLUSION: It can be postulated that in some RA patients the spontaneously high production of IL-1 beta may be associated with the up-regulated expression of c-Fos protein in PBMC. On the other hand the impairment of IL-1 beta production in RA induced by the PKC-dependent pathway, may be related to disturbances in c-Fos and c-Jun protein expression. This dysfunction seems to be compensated by some unknown mechanisms implicated in LPS signalling, which is known to involve not only the PKC-mediated pathway.
8484693 Early phenotypic activation of circulating helper memory T cells in scleroderma: correlati 1993 Apr OBJECTIVES: The differential expression of several accessory/activation molecules (CD26, CD29, CD45RA, CD25, MLR4, HLA-DR) on peripheral blood CD4+ and CD8+ T lymphocytes in patients with scleroderma was compared with that in controls and patients with other connective systemic diseases to look for evidence of the involvement of T cells in the disease process of scleroderma. METHODS: The two colour expression of surface molecules by circulating T cells was analysed with a panel of monoclonal antibodies and flow cytometry in 17 patients with scleroderma, 10 patients with systemic lupus erythematosus, and five patients with rheumatoid arthritis, and the results compared with those for 10 normal controls. The two colour T CD4+ phenotype was further compared between patients with active and quiescent disease in these patients with scleroderma. The coexpression of surface molecules by CD4+ T cells was also analysed by three colour flow cytometry in eight patients with scleroderma. RESULTS: Patients with scleroderma showed increased CD4+CD26+ and CD4+CD25+ percentages and absolute numbers and decreased CD8+CD29+ percentages compared with controls. Moreover, a significant correlation between the higher CD4+CD26+ T cell percentage and absolute cell numbers with disease activity was observed. Most of the CD4+ peripheral blood T cells from patients with scleroderma showed the CD26+CD45RA- phenotype by three colour flow cytometry analysis. CONCLUSIONS: The distinctive pattern of early helper memory T cell activation in these patients with rapidly evolving scleroderma supports the role of a T cell mediated mechanism in the progression of scleroderma.
8961381 Relationship between interleukin-8 and neutrophil adhesion molecules in rheumatoid arthrit 1996 To evaluate the role of interleukin-8 (IL-8) on the activation of neutrophils in rheumatoid arthritis (RA), we measured IL-8 and the adhesion molecules, L-selectin (CD62L), CD1 1b and CD18, on neutrophils in paired peripheral blood and synovial fluid of RA patients. Synovial fluid IL-8 levels were significantly increased compared to peripheral blood. L-selectin was split off and CD1 1b and CD 18 were upregulated on neutrophils in the synovial fluid. A positive correlation occurred between the IL-8 concentration and CD18 or CD1 1b densities on neutrophils in the synovial fluid (r = 0.75, P < 0.005 and r = 0.60, P < 0.05, respectively). Peripheral blood neutrophils of the patients were desensitised with IL-8 in vivo, as shown by the significantly lower L-selectin shedding after in vitro IL-8 stimulation: 1.6 times decrease for patients vs 3.2 for controls (P < 0.05). In conclusion, these results add further evidence for the role of IL-8 in the activation of neutrophils in RA.
8946814 Cyclophosphamide-induced acute liver failure requiring transplantation in a patient with g 1996 Nov Severe liver damage can occur after treatment with cyclophosphamide. The possible linkage to genetically deficient drug metabolic capacity is unknown. A 58-year-old woman with rheumatoid arthritis was treated with oral cyclophosphamide 50 mg twice daily for 2 months. Due to poor response the dose was doubled and liver failure requiring transplantation developed within weeks. After surgery PCR amplification using DNA from leukocytes showed that she was homozygous for the mutated allele CYP2D6B, which is predictive of the poor metaboliser phenotype for debrisoquine, occurring in 7% of Caucasians. Our patient may have accumulated high levels of the hepatotoxic 4-hydroxylated cyclophosphamide metabolite. Pharmacogenetic methods can help in exploring mechanisms of unexpected severe adverse effects.
1512759 Synoviocyte derived granulocyte macrophage colony stimulating factor mediates the survival 1992 Jul Synoviocytes have been shown to be effector cells capable of synthesizing and secreting a variety of cytokines and growth factors. We demonstrate here that synoviocyte derived conditioned medium has immunoregulatory properties as it enhances human peripheral blood lymphocyte survival in a dose dependent manner in vitro. The effect elicited by synoviocyte derived conditioned medium from patients with rheumatoid arthritis (RA) was greater than that induced by synoviocyte derived conditioned medium from patients with osteoarthritis. Granulocyte-macrophage colony stimulating factor (GM-CSF) was found in synoviocyte derived conditioned medium with significantly higher levels present in synoviocyte derived conditioned medium from patients with RA. Recombinant human GM-CSF induced survival of human lymphocytes in vitro and a monoclonal antibody to human GM-CSF fully abrogated synoviocyte derived conditioned medium induced survival. Our results demonstrate that synoviocyte derived GM-CSF may be important in the retention of lymphocytes, which is a central pathological characteristic of the rheumatoid joint.
7632088 Cellular immunity to cartilage link protein in patients with inflammatory arthritis and no 1995 Jun OBJECTIVES: To determine if increased T cell responses to articular cartilage link protein have any correlation with rheumatoid arthritis (RA), and if RA patients with increased responses to link protein also respond to a 17 amino acid peptide covering the 'arthritogenic' epitope in mycobacterial hsp65 which is homologous with link protein. METHODS: The reactivity of T cells from both peripheral blood and synovial fluid, to highly purified human cartilage link protein, hsp65, the 17 amino acid peptide, and bovine type II collagen was determined in patients with RA and nonarthritic controls, by measuring the rate of mononuclear cell proliferation in the presence and absence of antigen. RESULTS: Using peripheral blood mononuclear cells (PBMC), significant reactivity (stimulation index (SI) > 1.5) to link protein was found in 12 of 46 RA patients (26%), but in only four of 44 controls (9%). A greater proportion of RA patients (eight of 17:47%) were reactive to link protein when mononuclear cells from synovial fluid were tested. SI values, however, were generally low (0.5-3.1) and only one patient showed a PBMC response above a reference range of values calculated from the logarithmic values of the normal control population. No reactivity was observed against a 17 amino acid synthetic peptide including the arthritogenic epitope from the mycobacterial hsp65 to which T cell clones isolated from rats in the adjuvant arthritis model react. However, eight of nine RA patients and all of seven controls reacted to the intact hsp65. CONCLUSION: It remains unclear if T cell responses to link protein are involved in the pathogenesis of RA, but it is unlikely that T cells specific for the sequence homologous with the arthritogenic epitope in hsp65 are present in RA patients.
8898376 The repertoire of CD4+ CD28- T cells in rheumatoid arthritis. 1996 Sep BACKGROUND: While oligoclonality of circulating CD4- CD8 and of CD8+ T cells is not uncommon, clonal dominance within the CD4 compartment is not frequently found in healthy individuals. In contrast, the majority of patients with rheumatoid arthritis (RA) have clonally expanded CD4+ T cell populations. Previous studies have demonstrated that these clonogenic CD4+ T cells do not express the CD28 molecule. To examine the correlation between CD28 expression and clonal proliferation, we have analyzed the T cell receptor (TCR) diversity of CD4+ CD28- T cells in normal individuals and in RA patients. MATERIAL AND METHODS: The size of the peripheral blood CD4+ CD28- compartment was determined in 30 healthy individuals and 30 RA patients by two-color FACS analysis. In 10 RA patients and five controls with more than 2.5% CD4+ CD28- T cells, TCR BV gene segment usage was analyzed with 19 BV-specific antibodies. Oligoclonality was assessed in sorted CD4+ CD28+ and CD28- T cells using TCR BV-BC-specific polymerase chain reaction and size fractionation. Clonal dominance was confirmed by direct sequencing. RESULTS: The CD4+ CD28- T cell compartment was expanded to more than 2.5% in 70% of the RA patients and 30% of the normal individuals. Compared with the CD4+ CD28+ T cells, the TCR BV gene segment usage among CD4+ CD28- cells was grossly skewed with the dominance of single BV elements. Molecular TCR analysis provided evidence for oligoclonality in 17 of 21 expanded BV elements. In two unrelated RA patients who shared both HLA-DRB1 alleles, the TCR beta-chain sequences of dominant clonotypes were highly conserved. CONCLUSIONS: Oligoclonality is a characteristic feature of CD4+ CD28- T cells which are expanded in some healthy individuals and in the majority of RA patients. The lack of CD28 expression is a common denominator of CD4+, CD8+, and CD4- CD8- T cells prone to develop clonal dominance. The limited TCR diversity of clonal CD4+ CD28- populations in RA patients suggests that these T cells recognize a limited spectrum of antigens. The fact that the majority of individuals with marked expansions and oligoclonality of CD4+ CD28- T cells are RA patients suggests a role for these unusual lymphocytes in the pathogenetic events leading to RA.
8090577 [Interleukin-4: from B-lymphocyte to fibroblast]. 1994 Mar Interleukin-4 (IL-4) has been characterized in 1982 by its ability to induce the proliferation of anti-IgM stimulated B-lymphocytes and IgG1 secretion by these same cells after activation by lipopolysaccharide. It's activity on B-cells explain that it received the former names of B-Cell Growth Factor-1 (BCGF-1) or B-Cell Stimulatory Factor-1 (BSF-1). More recent works have shown that IL-4 exerts pleiotropic effects on a large number of cells. Particularly, it is able to activate the production of extracellular matrix components by fibroblasts. The aim of the present paper is to review main data about this cytokine, with a particular emphasis on its role on the regulation of connective tissue cell activities and on its possible implication in pathophysiological events such as fibrosis, wound healing, and tumor invasion.
7734365 Epinephrine test and plasma elastase as diagnostic tools in a patient with CD3+ large gran 1995 Mar Large granular lymphocytes (LGL) proliferation is characterized by expansion of cytotoxic lymphocytes and associated with neutropenia. In a case of CD3+ LGL-proliferation the epinephrine stimulation test (EST) induced a striking elevation of CD3+, CD8+, CD57+ LGL in peripheral blood from 2.7 x 10(9)/l to 20 x 10(9)/l and might be an additional diagnostic tool in patients with normal or low absolute numbers of circulating LGL. After treatment with steroids, plasma elastase--a marker of neutrophil destruction--decreased from 162 to 40 micrograms/l (normal < 47 micrograms/l) which correlated well with a simultaneous increase in peripheral neutrophil counts from 0.14 to 1.0 x 10(9)/l. This finding supports the hypothesis that neutropenia in CD3+ LGL proliferation is due to neutrophil destruction, possibly mediated by LGL.
1642224 A prospective randomized study of the injurious effects of aspirin and naproxen on the gas 1992 Aug A prospective double-blind randomized placebo-controlled study was conducted to compare the injurious effects of aspirin and naproxen on the gastroduodenal mucosa. Patients with rheumatoid arthritis attending the immunology clinic of a tertiary care center were included in the study. Ninety consecutive patients were randomized to receive aspirin, naproxen, or placebo. Clinical evaluation was done every 2 wk. Upper gastrointestinal endoscopy, biopsies from the gastric antrum and duodenum for histological examination, and Helicobacter pylori studies were done at entry and after 2 months. The number of patients with dyspeptic symptoms was similar in the aspirin (12) and naproxen (9) groups. In both cases, however, it was higher (p less than 0.01) than in the placebo group (none). Naproxen was associated with a higher score of endoscopic abnormalities in the gastric body (0.6 +/- 1.3) than aspirin (0.2 +/- 0.6) or placebo (0.03 +/- 0.18). H. pylori was present in a similar proportion of patients in the three groups (33-43%). A greater fall in hemoglobin was observed with aspirin (0.35 +/- 0.48 g%) and naproxen (0.44 +/- 0.53 g%) than with placebo (0.09 +/- 0.4 g%). The present study suggests that aspirin and naproxen produce a similar degree of injury to the gastroduodenal mucosa.
8235291 Immunoglobulin G and serum albumin isolated from the articular cartilage of patients with 1993 The present study was undertaken to identify the cartilage matrix molecules that are bound with intermolecular disulfide bonds to IgG and serum albumin molecules recovered from the articular cartilage of patients with rheumatoid arthritis (RA) or osteoarthritis (OA). The cartilage specimens were extracted sequentially with three changes of neutral buffer, three changes of 6 M guanidine hydrochloride and then partially degraded with bacterial collagenase. The extracted IgG and albumin, along with matrix molecules bound to these proteins, were isolated with affinity chromatography using antibodies to IgG or human serum albumin conjugated to agarose beads. The isolated materials were characterized with sodium dodecyl sulfate polyacrylamide gel electrophoresis and transfer blotting, using specific antibodies to IgG, albumin, and proteoglycans. In the isolated materials, heteropolymers with IgG or albumin were identified. These polymers contained keratan sulfate and less frequently chondroitin-4-sulfate and chondroitin-6-sulfate. These findings identified the keratan sulfate rich proteoglycans, prevalent at the surface of joint cartilage, as the most common cartilage matrix molecules that are covalently bound to IgG or to serum albumin by disulfide bonds in the articular cartilage of patients with RA or OA.
8463577 Tension band arthrodesis of small joints in the hand. 1993 Mar Two-hundred three patients underwent 290 tension band arthrodeses of the metacarpophalangeal and proximal interphalangeal joints of the hand. Nine patients (3%) failed to achieve bony union, four had painless pseudarthroses, and one patient had a small finger amputation. Twenty-five fusions (9%) required hardware removal. There were 10 superficial infections (all responded to oral antibiotic therapy), and three fusions were malrotated. Tension band arthrodesis is our choice for fusion of the metacarpophalangeal and proximal interphalangeal joints. It is reliable and provides stable fixation, pins do not protrude, and external splinting is unnecessary in the cooperative patient.