Wiley
0004-3591
1529-0131
Cơ quản chủ quản: N/A
Lĩnh vực:
Các bài báo tiêu biểu
High mobility group box chromosomal protein 1, a DNA binding cytokine, induces arthritis Abstract Objective To examine the potential role of high mobility group box chromosomal protein 1 (HMGB‐1) in the pathogenesis of arthritis. Methods Mice were injected intraarticularly with 1 μg or 5 μg of HMGB‐1. Joints were dissected on days 4, 7, and 28 after injection and were evaluated histopathologically and immunohistochemically. To investigate the importance of different white blood cell populations for the development of arthritis, in vivo cell depletion procedures were performed. In addition, spleen cells were cultured in the presence of HMGB‐1, and nuclear factor κB (NF‐κB) activation was detected by electrophoretic mobility shift assay. Results Injection of recombinant HMGB‐1 (rHMGB‐1) into different mouse strains resulted in an overall frequency of arthritis in 80% of the animals. The inflammation was characterized by mild to moderate synovitis and lasted for at least 28 days. The majority of cells found in the inflamed synovium were Mac‐1+ macrophages, whereas only a few CD4+ lymphocytes were detected. Pannus formation was observed in some cases 7 and 28 days after HMGB‐1 injection. No significant differences were found with respect to incidence and severity of arthritis between mice depleted of monocytes, granulocytes, or lacking T/B lymphocytes. However, combined removal of monocytes and neutrophils resulted in a 43% lower incidence of arthritis. Mice rendered deficient in the interleukin‐1 (IL‐1) receptor did not develop inflammation upon challenge with HMGB‐1. In vitro data corroborate this finding, showing that rHMGB‐1 activated NF‐κB, a major pathway leading to IL‐1 production. Conclusion Our results indicate that HMGB‐1 is not a mere expression of inflammatory responses, but on its own, it triggers joint inflammation by activating macrophages and inducing production of IL‐1 via NF‐κB activation.
Tập 48 Số 6 - Trang 1693-1700 - 2003
Special article the economic cost and social and psychological impact of musculoskeletal conditions Abstract Objective. To provide an indication of the economic, social, and psychological impact of musculoskeletal conditions in the United States.Methods. Review of the literature combined with estimates of data concerning health care utilization and acute and chronic disability due to musculoskeletal conditions, from the 1990–1992 National Health Interview Survey.Results. The cost of musculoskeletal conditions was $149.4 billion in 1992, of which 48% was due to direct medical care costs and the remainder was due to indirect costs resulting from wage losses. This amount translates to ˜2.5% of the Gross National Product, a sharp rise since the prior studies, even if part of the increase is an artifact of improved accounting methods. Each year, persons with musculoskeletal conditions make 315 million physician visits, have more than 8 million hospital admissions, and experience ˜1.5 billion days of restricted activity. Approximately 42% of persons with musculoskeletal conditions–more than 17 million in all–are limited in their activities.Conclusion. The economic and social costs of musculoskeletal conditions are substantial. These conditions are responsible for a sizable amount of health care use and disability, and they significantly affect the psychological status of the individuals with the conditions as well as their families.
Tập 38 Số 10 - Trang 1351-1362 - 1995
Predictors of survival in systemic sclerosis (Scleroderma) Abstract We conducted followup of 264 patients with definite systemic sclerosis (SSc) who were entered into the multicenter Scleroderma Criteria Cooperative Study (SCCS) during 1973–1977. At the end of the study (average 5.2 years of followup), 38% were known to be alive, 50% were dead (68% of these deaths definitely related to SSc), and 12% were lost to followup. Survival analyses of 484 demographic, clinical, and laboratory items recorded at entry into the SCCS (within 2 years of physician diagnosis of SSc) were performed. Survival declined linearly, and the cumulative survival rate was <80% at 2 years, 50% at 8.5 years, and 30% at 12 years after entry. Analysis using combinations of entry variables identifying organ system involvement confirmed that renal, cardiac, pulmonary, and gastrointestinal involvement in SSc predicted reduced survival; however, data on organ system involvement at study entry could not be used to consistently predict which organ system would ultimately be involved as the primary cause of death. By survival tree analysis, the individual entry variables best predicting reduced survival included older age (>64 years), reduced renal function (blood urea nitrogen >16 mg/dl), anemia (hemoglobin ≤11 gm/dl), reduced pulmonary diffusing capacity for carbon monoxide (≤50% of predicted), reduced total serum protein level (≤6 gm/dl), and reduced pulmonary reserve (forced vital capacity <80% with hemoglobin >14 gm/dl or forced vital capacity <65% with hemoglobin ≤14 gm/dl). Cox proportional hazards model analysis confirmed these results. Different combinations of variables led to markedly different survival rates. The poorest prospects for survival were in patients with SSc who were ≤64 years old with a hemoglobin level ≤11 gm/dl, and in those >64 years old with a blood urea nitrogen level >16 mg/dl. These results may be useful in predicting individual patients at risk for shortened survival.
Tập 34 Số 4 - Trang 403-413 - 1991
Isolated diffusing capacity reduction in systemic sclerosis Abstract Objective. To determine the long‐term outcome of patients with systemic sclerosis (SSc) and an isolated reduction in the diffusing capacity for carbon monoxide (DLco) at the time of initial evaluation.Methods. Patients with an isolated reduction in DLco (i.e., normal forced vital capacity [FVC] and normal ratio of the forced expiratory volume in one second [FEV1 ] to the FVC) on initial evaluation were identified from among 815 patients with SSc who were carefully followed up throughout their illness. We requested that patients have repeat pulmonary function testing (PFT), and the outcomes of these tests, as well as cardiopulmonary and survival outcomes, were determined.Results. An isolated reduction in DLco, with a normal FVC was detected in 152 (19%) of the 815 patients. A subset of those with an isolated reduction in DLco (11%) developed isolated pulmonary hypertension and had severely reduced survival rates. Pulmonary hypertension was strongly associated with an initial DLco of < 55% of predicted normal and a FVC (% predicted)/DLco (% predicted) ratio of > 1.4. Among all patients in whom this ratio was > 1.4, 22% developed isolated pulmonary hypertension, compared with only 2% of those whose ratio was <1.4 (P < 0.01). Of the 152 patients with isolated DLco reduction, 73 (48%) underwent PFTs a mean of 5.4 years (range 2.0–13.2) after the initial PFT. Only 6 (8%) of these 73 patients ever had serious pulmonary disease: 5 had isolated pulmonary hypertension, and 1 had severe pulmonary fibrosis. Half of the patients with a low initial DLco demonstrated a significant improvement (>20%) at followup testing that could not be explained by the demographic, clinical, or laboratory findings at the first visit.Conclusion. Isolated reduction in DLco is a frequent abnormality in SSc. Overall, it is associated with a good prognosis for survival and for pulmonary morbidity. A small subset of patients (11%) who have a very low DLco (<55% of predicted) have developed isolated pulmonary hypertension, all of whom had limited scleroderma.
Tập 35 Số 7 - Trang 765-770 - 1992
Pulmonary hypertension in the crest syndrome variant of systemic sclerosis Abstract Pulmonary hypertension (PHT) occurred in 59 (9%) of 673 systemic sclerosis patients seen between 1963 and 1983. In 30 patients, all with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, telangiectasias), the pulmonary hypertension was isolated, i.e., independent of other pulmonary or cardiac conditions. In 20 patients, isolated PHT was demonstrated by cardiac catheterization. All had normal or only mildly decreased lung volumes, and mild or no pulmonary interstitial fibrosis on chest roentgenogram. In comparison with 287 CREST syndrome patients without PHT, these 20 patients had markedly reduced diffusing capacity for carbon monoxide (DLco) (mean 39% of predicted normal). In 6 patients, the low DLco antedated clinical evidence of PHT by 1–6 years. At autopsy there was marked intimal fibrosis with hyalinization and smooth muscle hypertrophy in the small‐ and medium‐sized arteries, without significant parenchymal fibrosis or inflammation. Patients with isolated PHT did not respond favorably to vasodilators and had a very poor prognosis, with a 2‐year cumulative survival rate of 40%. A DLco < 45% of predicted in the absence of pulmonary interstitial fibrosis may be an important predictor of the subsequent development of isolated PHT.
Tập 29 Số 4 - Trang 515-524 - 1986
Pulmonary involvement in systemic sclerosis (scleroderma) Abstract One hundred sixty‐five nonsmoking systemic sclerosis patients were evaluated by pulmonary function testing. Restrictive lung disease and an isolated reduction of the diffusing capacity of carbon monoxide were the most frequent abnormalities. Patients with the CREST syndrome (calcinosis, Raynaud's phenomenon, esophageal dysmotility, sclerodactyly, and telangiectasias) had a similar frequency and severity of pulmonary involvement compared with the patients who had diffuse scleroderma. CREST syndrome patients with restrictive lung disease rarely had the anticentromere antibody and had more skin and joint involvement of their hands, compared with other CREST syndrome patients. Dyspnea and rales were most commonly found in patients with restrictive lung disease. Fibrosis, shown on chest radiograph, and pulmonary function abnormalities correlated poorly with each other. Dyspnea was associated with restrictive disease, and rales were more commonly found in patients with fibrosis. Patients with a restrictive abnormality had the worst prognosis, with a 5‐year survival rate of 58%, although death from pulmonary causes was uncommon. Comparison of these nonsmoking patients with 137 scleroderma patients who smoked, seen during the same time period, revealed more frequent and severe obstructive changes in smokers. Smoking patients with restrictive lung disease had more severe disease than nonsmoking patients. The single breath diffusing capacity for carbon monoxide was significantly decreased in the patients who smoked compared with the nonsmokers. These data confirm that pulmonary function abnormalities are common in patients with systemic sclerosis including CREST syndrome. Smoking appears to have an additive deleterious effect on pulmonary function and should be strongly discouraged.
Tập 28 Số 7 - Trang 759-767 - 1985
Normotensive renal failure in systemic sclerosis Abstract Of 140 patients with “scleroderma renal crisis” encountered during a 33‐year period, 15 of 131 (11%) whose blood pressures were recorded were normotensive during this complication. In comparison with 116 patients with hypertension, the normotensive patients significantly more often had microangiopathic hemolytic anemia (90% versus 38%) and thrombocytopenia (83% versus 21%). Pulmonary hemorrhage occurred in 6 normotensive patients. More normotensive patients had received high doses of corticosteroids (prednisone gE;30 mg/day) during the 2 months immediately preceding renal crisis (64% versus 16%). A role for corticosteroids in precipitating renal crisis is suggested. The 12‐month survival was significantly reduced in the normotensive patients (13% versus 35%).
Tập 32 Số 9 - Trang 1128-1134 - 1989
Close relationship between systemic lupus erythematosus and thrombotic thrombocytopenic purpura in childhood: Comment on the article by Brunner et al
Tập 46 Số 5 - Trang 1410-1410 - 2002
Intraarticular injection of platelet‐rich plasma reduces inflammation in a pig model of rheumatoid arthritis of the knee joint Abstract Objective Treatment options for rheumatoid arthritis range from symptomatic approaches to modern molecular interventions such as inhibition of inflammatory mediators. Inhibition of inflammation by platelet‐rich plasma (PRP) has been proposed as a treatment for tendinitis and osteoarthritis. The present study was undertaken to investigate the effect of PRP on antigen‐induced arthritis (AIA) of the knee joint in a large animal model. Methods Six‐month‐old pigs (n = 10) were systemically immunized by bovine serum albumin (BSA) injection, and arthritis was induced by intraarticular BSA injection. PRP was injected into the knee joints of 5 of the animals after 2 weeks. An additional 5 animals received no systemic immunization (controls). Signs of arthritis were documented by plain histologic analysis, Safranin O staining, and immunohistochemistry analysis for type II collagen (CII), interleukin‐6 (IL‐6), and vascular endothelial growth factor (VEGF). Interleukin‐1β (IL‐1β), IL‐6, tumor necrosis factor α (TNFα), VEGF, and insulin‐like growth factor 1 (IGF‐1) protein content was measured by Luminex assay. Results In the pigs with AIA, plain histologic analysis revealed severe arthritic changes in the synovium. Safranin O and CII staining showed decreased proteoglycan and CII content in cartilage. Immunohistochemistry analysis revealed increased levels of IL‐6 and VEGF in synovium and cartilage, and protein concentrations of IL‐6, VEGF, IL‐1β, and IGF‐1 in synovium and cartilage were elevated as well; in addition, TNFα protein was increased in cartilage. Treatment with PRP led to attenuation of these arthritic changes in the synovium and cartilage. Conclusion We have described a porcine model of AIA. Experiments using this model demonstrated that PRP can attenuate arthritic changes as assessed histologically and based on protein synthesis of typical inflammatory mediators in the synovial membrane and cartilage.
Tập 63 Số 11 - Trang 3344-3353 - 2011
Antiinflammatory and chondroprotective effects of intraarticular injection of adipose‐derived stem cells in experimental osteoarthritis Abstract Objective In experimental collagenase‐induced osteoarthritis (OA) in the mouse, synovial lining macrophages are crucial in mediating joint destruction. It was recently shown that adipose‐derived stem cells (ASCs) express immunosuppressive characteristics. This study was undertaken to explore the effect of intraarticular injection of ASCs on synovial lining thickness and its relation to joint pathology in experimental mouse OA. Methods ASCs were isolated from fat surrounding the inguinal lymph nodes and cultured for 2 weeks. Experimental OA was induced by injection of collagenase into the knee joints of C57BL/6 mice. OA phenotypes were measured within 8 weeks after induction. Histologic analysis was performed, and synovial thickening, enthesophyte formation, and cartilage destruction were measured in the knee joint. Results ASCs were injected into the knee joints of mice 7 days after the induction of collagenase‐induced OA. On day 1, green fluorescent protein–labeled ASCs were attached to the lining layer in close contact with macrophages. Thickening of the synovial lining, formation of enthesophytes associated with medial collateral ligaments, and formation of enthesophytes associated with cruciate ligaments were significantly inhibited on day 42 after ASC treatment, by 31%, 89%, and 44%, respectively. Destruction of cartilage was inhibited on day 14 (65%) and day 42 (35%). In contrast to early treatment, injection of ASCs on day 14 after OA induction showed no significant effect on synovial activation or joint pathology on day 42. Conclusion These findings indicate that a single injection of ASCs into the knee joints of mice with early‐stage collagenase‐induced OA inhibits synovial thickening, formation of enthesophytes associated with ligaments, and cartilage destruction.
Tập 64 Số 11 - Trang 3604-3613 - 2012