bluuebunny/crossref_metadata_2025_split huggingface dataset:
Antineutrophil cytoplasmic antibody–associated vasculitides: Could geographic patterns be explained by ambient ultraviolet radiation?
Authors: Gatenby Paul A. , Lucas Robyn M. , Engelsen Ola , Ponsonby Anne‐Louise , Clements Mark 
Published: September 2009

AbstractObjectiveThis ecological study describes and quantifies the association between ambient ultraviolet (UV) radiation levels, including daily winter vitamin D effective UV radiation levels and the incidence of the 3 antineutrophil cytoplasmic antibody–associated vasculitides (AAVs): Wegener's granulomatosis (WG), microscopic polyangiitis (MPA), and Churg‐Strauss syndrome (CSS). Latitudinal variation in occurrence of the AAVs, especially WG, has been previously reported. For other autoimmune diseases such as multiple sclerosis and type 1 diabetes mellitus, inverse associations with latitude are hypothesized to indicate a causative role for low UV radiation exposure, possibly acting via vitamin D status.MethodsPublished epidemiologic studies provided data on incident cases, total population of study regions, age‐specific incidence rates, and study location. From these data and online age‐specific population data, we calculated crude incidence rates, the expected number of cases (to control for possible age confounding), and measures of ambient UV radiation. Negative binomial regression models were used to calculate the incidence rate ratio (IRR) for a 1,000 joules/m2 increase in ambient UV radiation.ResultsThe incidence of WG and CSS increased with increasing latitude and decreasing ambient UV radiation, with a stronger and more consistent effect across different UV radiation measures for WG, e.g., for average daily ambient clear sky erythemal UV radiation (WG: IRR 0.64 [95% confidence interval (95% CI) 0.44–0.94], P = 0.02; CSS: IRR 0.67 [95% CI 0.43–1.05], P = 0.08; MPA: IRR 1.16 [95% CI 0.92–1.47], P = 0.22). There was no apparent latitudinal variation in MPA incidence.ConclusionOur findings are consistent with a protective immunomodulatory effect of ambient UV radiation on the onset of WG and CSS. We discuss possible mechanisms, including the effect of vitamin D on the immune system.
Abnormal function of high‐density lipoprotein is associated with poor disease control and an altered protein cargo in rheumatoid arthritis
Authors: Charles‐Schoeman Christina , Watanabe Junji , Lee Yuen Yin , Furst Daniel E. , Amjadi Sogol , Elashoff David , Park Grace , McMahon Maureen , Paulus Harold E. , Fogelman Alan M. , Reddy Srinivasa T. 
Published: September 2009

AbstractObjectiveTo characterize the antiinflammatory function of high‐density lipoprotein (HDL) in patients with rheumatoid arthritis (RA) and to identify specific differences in HDL‐associated proteins and enzymes that distinguish proinflammatory HDL from normal, antiinflammatory HDL.MethodsWe studied 132 RA patients. The antiinflammatory function of HDL was assessed by a cell‐free assay, and proinflammatory HDL was defined by an HDL inflammatory index ≥1. Plasma and HDL‐associated protein levels of apolipoprotein A‐I (Apo A‐I), haptoglobin, hemopexin, hemoglobin, and myeloperoxidase (MPO) were measured by direct and sandwich enzyme‐linked immunosorbent assays, respectively. Lecithin:cholesterol acyltransferase (LCAT) activity was measured by a commercially available assay.ResultsAge, disease activity, the presence of erosive disease, non‐Caucasian race, and smoking were significantly associated with proinflammatory HDL on multivariate analysis. Patients with proinflammatory HDL had higher measures of systemic inflammation, and a significant correlation was observed between RA disease activity (using the Disease Activity Score in 28 joints) and the HDL inflammatory index (r = 0.54, P < 0.0001). Compared with patients with antiinflammatory HDL, patients with proinflammatory HDL had significantly higher levels of haptoglobin, hemoglobin, Apo A‐I, and MPO associated with HDL (P < 0.05 for all comparisons except MPO, which was P = 0.05). LCAT activity was lowest in patients with proinflammatory HDL, but was also significantly reduced in RA patients with antiinflammatory HDL as compared with healthy controls (P = 0.001).ConclusionProinflammatory HDL in this RA patient cohort was associated with active disease and an altered protein cargo as compared with antiinflammatory HDL in RA patients and in healthy controls. The antiinflammatory function of HDL was inversely correlated with systemic inflammation in RA patients and may warrant further investigation as a mechanism by which active RA increases cardiovascular morbidity and mortality.
Induction of bovine articular chondrocyte senescence with oxidized low‐density lipoprotein through lectin‐like oxidized low‐density lipoprotein receptor 1
Authors: Zushi Satoshi , Akagi Masao , Kishimoto Hideki , Teramura Takeshi , Sawamura Tatsuya , Hamanishi Chiaki 
Published: September 2009

AbstractObjectiveFindings of recent in vivo and in vitro studies suggest that oxidized low‐density lipoprotein (ox‐LDL) plays a role in the degeneration of cartilage. The purpose of this study was to determine whether ox‐LDL induces chondrocyte senescence through binding to lectin‐like ox‐LDL receptor 1 (LOX‐1).MethodsThe effects of ox‐LDL on senescence of cultured bovine articular chondrocytes (BACs) were investigated by observing senescence‐associated (SA) β‐galactosidase (β‐gal) activity, cell proliferation activity, and telomerase activity. Telomerase activity was measured after adding LY294002 (a specific inhibitor of phosphatidylinositol 3‐kinase [PI3K]) or after adding insulin‐like growth factor 1 (IGF‐1; an activator of PI3K) plus ox‐LDL to the culture medium to elucidate the involvement of the PI3K/Akt pathway. Immunoblot analysis was used to investigate whether ox‐LDL affects the phosphorylation of Akt. To ascertain whether these effects were attributable to ox‐LDL binding to LOX‐1, BACs were preincubated with TS‐20, an anti‐bovine LOX‐1 blocking antibody.ResultsThe activity of SA β‐gal was increased and the incorporation of bromodeoxyuridine into BACs was decreased by ox‐LDL in a dose‐dependent manner. The telomerase activity of BACs was suppressed by the addition of ox‐LDL in a time‐ and dose‐dependent manner. LY294002 suppressed the telomerase activity of BACs, and IGF‐1 reversed the ox‐LDL–induced suppression of telomerase activity. In addition, ox‐LDL rapidly decreased the amount of phosphorylated Akt in BACs. Pretreatment of cultured BACs with TS‐20 recovered these effects.ConclusionThese data show that ox‐LDL binding to LOX‐1 induces stress‐induced premature senescence of chondrocytes and results in suppression of telomerase activity by inactivating the PI3K/Akt pathway. Oxidized LDL may play an important role in the pathogenesis of osteoarthritis by inducing chondrocyte senescence.
Induction of an antiinflammatory effect and prevention of cartilage damage in rat knee osteoarthritis by CF101 treatment
Authors: Bar‐Yehuda S. , Rath‐Wolfson L. , Del Valle L. , Ochaion A. , Cohen S. , Patoka R. , Zozulya G. , Barer F. , Atar E. , Piña‐Oviedo S. , Perez‐Liz G. , Castel D. , Fishman P. 
Published: September 2009

AbstractObjectiveStudies have suggested that rheumatoid arthritis (RA) and osteoarthritis (OA) share common characteristics. The highly selective A3 adenosine receptor agonist CF101 was recently defined as a potent antiinflammatory agent for the treatment of RA. The purpose of this study was to examine the effects of CF101 on the clinical and pathologic manifestations of OA in an experimental animal model.MethodsOA was induced in rats by monosodium iodoacetate, and upon disease onset, oral treatment with CF101 (100 μg/kg given twice daily) was initiated. The A3 adenosine receptor antagonist MRS1220 (100 μg/kg given twice daily) was administered orally, 30 minutes before CF101 treatment. The OA clinical score was monitored by knee diameter measurements and by radiographic analyses. Histologic analyses were performed following staining with hematoxylin and eosin, Safranin O–fast green, or toluidine blue, and histologic changes were scored according to a modified Mankin system. Signaling proteins were assayed by Western blotting; apoptosis was detected via immunohistochemistry and TUNEL analyses.ResultsCF101 induced a marked decrease in knee diameter and improved the changes noted on radiographs. Administration of MRS1220 counteracted the effects of CF101. CF101 prevented cartilage damage, osteoclast/osteophyte formation, and bone destruction. In addition, CF101 markedly reduced pannus formation and lymphocyte infiltration. Mechanistically, CF101 induced deregulation of the NF‐κB signaling pathway, resulting in down‐regulation of tumor necrosis factor α. Consequently, CF101 induced apoptosis of inflammatory cells that had infiltrated the knee joints; however, it prevented apoptosis of chondrocytes.ConclusionCF101 deregulated the NF‐κB signaling pathway involved in the pathogenesis of OA. CF101 induced apoptosis of inflammatory cells and acted as a cartilage protective agent, which suggests that it would be a suitable candidate drug for the treatment of OA.
Plasmin immunization preferentially induces potentially prothrombotic IgG anticardiolipin antibodies in MRL/MpJ mice
Authors: Ede Kaleo , Hwang Kwan‐Ki , Wu Chen‐Ching , Wu Meifang , Yang Yao‐Hsu , Lin Wei‐Shiang , Chien Daniel , Chen Pei‐Chih , Tsao Betty P. , McCurdy Deborah K. , Chen Pojen P. 
Published: September 2009

AbstractObjectiveTo test the hypothesis, utilizing 2 experimental mouse models, that plasmin is an important autoantigen that drives the production of certain IgG anticardiolipin (aCL) antibodies in patients with the antiphospholipid syndrome.MethodsBALB/cJ and MRL/MpJ mice were immunized with Freund's complete adjuvant in the presence or absence of human plasmin. The mouse sera were analyzed for production of IgG antiplasmin, IgG aCL, and IgG anti–β2‐glycoprotein I (anti‐β2GPI) antibodies. IgG monoclonal antibodies (mAb) were generated from the plasmin‐immunized MRL/MpJ mice with high titers of aCL, and these 10 mAb were studied for their binding properties and functional activity in vitro.ResultsPlasmin‐immunized BALB/cJ mice produced high titers of IgG antiplasmin only, while plasmin‐immunized MRL/MpJ mice produced high titers of IgG antiplasmin, IgG aCL, and IgG anti‐β2GPI. Both strains of mice immunized with the adjuvant alone did not develop IgG antiplasmin or IgG aCL. All 10 of the IgG mAb bound to human plasmin and cardiolipin, while 4 of 10 bound to β2GPI, 3 of 10 bound to thrombin, and 4 of 10 bound to the activated coagulation factor X (FXa). Functionally, 4 of the 10 IgG mAb inhibited plasmin activity, 1 of 10 hindered inactivation of thrombin by antithrombin III, and 2 of 10 inhibited inactivation of FXa by antithrombin III.ConclusionPlasmin immunization leads to production of IgG antiplasmin, aCL, and anti‐β2GPI in MRL/MpJ mice, but leads to production of only IgG antiplasmin in BALB/cJ mice. IgG mAb generated from plasmin‐immunized MRL/MpJ mice bind to various antigens and exhibit procoagulant activity in vitro. These results suggest that plasmin may drive potentially prothrombotic aCL in genetically susceptible individuals.
Skeletal health among African Americans with recent‐onset rheumatoid arthritis
Authors: Curtis J. R. , Arora T. , Donaldson M. , Alarcón G. S. , Callahan L. F. , Moreland L. W. , Bridges S. L. , Mikuls T. R. 
Published: September 2009

AbstractObjectiveAfrican Americans with rheumatoid arthritis (RA) may be at increased fracture risk. We applied the World Health Organization (WHO) Fracture Risk Assessment Tool (FRAX) and National Osteoporosis Foundation (NOF) guidelines to a cohort of African Americans with early RA to identify which patients were recommended for osteoporosis treatment.MethodsRisk factors and bone mineral density (BMD) were assessed in a cohort of African Americans with RA. The WHO FRAX tool estimated 10‐year fracture risk. Patients were risk stratified using FRAX without BMD to identify which individuals might be most efficiently targeted for BMD testing.ResultsParticipants (n = 324) had a mean age of 51 years and included 81% women. There were no associations of RA disease characteristics with BMD. The proportion of patients recommended for osteoporosis treatment varied from 3–86%, depending on age and body mass index (BMI). Ten‐year fracture risk calculated with BMI only was generally the same or higher than fracture risk calculated with BMD; adding BMD data provided the most incremental value to risk assessment in patients 55–69 years of age with low/normal BMI, and in those ≥70 years of age with BMI ≥30 kg/m2.ConclusionA high proportion of African Americans with RA were recommended for treatment under the 2008 NOF guidelines. FRAX without BMD identified low‐risk patients accurately. Systematic application of FRAX to screen high‐risk groups such as patients with RA may be used to target individuals for BMD testing and reduce the use of unnecessary tests and treatments.
CCR5 is involved in resolution of inflammation in proteoglycan‐induced arthritis
Authors: Doodes Paul D. , Cao Yanxia , Hamel Keith M. , Wang Yumei , Rodeghero Rachel L. , Kobezda Tamas , Finnegan Alison 
Published: September 2009

AbstractObjectiveCCR5 and its ligands (CCL3, CCL4, and CCL5) may play a role in inflammatory cell recruitment into the joint. However, it was recently reported that CCR5 on T cells and neutrophils acts as a decoy receptor for CCL3 and CCL5 to assist in the resolution of inflammation. The aim of this study was to determine whether CCR5 functions as a proinflammatory or antiinflammatory mediator in arthritis, by examining the role of CCR5 in proteoglycan (PG)–induced arthritis (PGIA).MethodsArthritis was induced by immunizing wild‐type (WT) and CCR5‐deficient (CCR5−/−) BALB/c mice with human PG in adjuvant. The onset and severity of PGIA were monitored over time. Met‐RANTES was used to block CCR5 in vivo. Arthritis was transferred to SCID mice, using spleen cells from arthritic WT and CCR5−/− mice. The expression of cytokines and chemokines was measured by enzyme‐linked immunosorbent assay.ResultsIn CCR5−/− mice and WT mice treated with the CCR5 inhibitor Met‐RANTES, exacerbated arthritis developed late in the disease course. The increase in arthritis severity in CCR5−/− mice correlated with elevated serum levels of CCL5. However, exacerbated arthritis was not intrinsic to the CCR5−/− lymphoid cells, because the arthritis that developed in SCID mouse recipients was similar to that in WT and CCR5−/− mice. CCR5 expression in the SCID mouse was sufficient to clear CCL5, because serum levels of CCL5 were the same in SCID mouse recipients receiving cells from either WT or CCR5−/− mice.ConclusionThese data demonstrate that CCR5 is a key player in controlling the resolution of inflammation in experimental arthritis.
Parathyroid hormone 1–34 inhibits terminal differentiation of human articular chondrocytes and osteoarthritis progression in rats
Authors: Chang Je‐Ken , Chang Ling‐Hwa , Hung Shao‐Hung , Wu Shun‐Cheng , Lee Hsin‐Yi , Lin Yi‐Shan , Chen Chung‐Hwan , Fu Yin‐Chih , Wang Gwo‐Jaw , Ho Mei‐Ling 
Published: September 2009

AbstractObjectiveParathyroid hormone 1–34 (PTH[1–34]), a parathyroid hormone analog, shares the same receptor, PTH receptor 1, with parathyroid hormone–related peptide (PTHrP). This study was undertaken to address the hypothesis that PTH(1–34) inhibits terminal differentiation of articular chondrocytes and in turn suppresses the progression of osteoarthritis (OA).MethodsWe studied the effect of PTH(1–34) on human articular chondrocytes with azacytidine (azaC)–induced terminal differentiation in vitro and on papain‐induced OA in the knee joints of rats. In the in vitro study, we measured the levels of messenger RNA for SOX9, aggrecan, type II collagen, type X collagen, alkaline phosphatase (AP), Indian hedgehog (IHH), Bcl‐2, and Bax by real‐time polymerase chain reaction, levels of glycosaminoglycan (GAG) by dimethylmethylene blue assay, and rate of apoptosis by TUNEL staining. In the in vivo study, we evaluated the histologic changes in GAG, type II collagen, type X collagen, and chondrocyte apoptosis in the articular cartilage of rat knees.ResultsAzaC induced terminal differentiation of human chondrocytes, including down‐regulation of aggrecan, type II collagen, and GAG and up‐regulation of type X collagen, alkaline phosphatase, and IHH. Apoptosis was reversed by 3–10 days of treatment with 10 nM PTH(1–34). SOX9 expression was not changed by either azaC or PTH(1–34) treatment. Bcl‐2 and Bax were up‐regulated on day 10 and day 14, respectively, after azaC induction of terminal differentiation, but PTH(1–34) treatment did not reverse this effect. Furthermore, PTH(1–34) treatment reversed papain‐induced OA changes (decreasing GAG and type II collagen, and increasing type X collagen and chondrocyte apoptosis) in the knee joints of rats.ConclusionOur findings indicate that PTH(1–34) inhibits the terminal differentiation of human articular chondrocytes in vitro and inhibits progression of OA in rats in vivo, and may be used to treat OA.
Human inflammatory synovial fibroblasts induce enhanced myeloid cell recruitment and angiogenesis through a hypoxia‐inducible transcription factor 1α/vascular endothelial growth factor–mediated pathway in immunodeficient mice
Authors: del Rey Manuel J. , Izquierdo Elena , Caja Sergio , Usategui Alicia , Santiago Begoña , Galindo María , Pablos José L. 
Published: September 2009

AbstractObjectiveHyperplasia and phenotypic changes in fibroblasts are often observed in chronic inflammatory lesions, and yet the autonomous pathogenic contribution of these changes is uncertain. The purpose of this study was to analyze the intrinsic ability of fibroblasts from chronically inflamed synovial tissue to drive cell recruitment and angiogenesis.MethodsFibroblasts from patients with rheumatoid arthritis (RA) or osteoarthritis (OA), as well as fibroblasts from healthy synovial tissue and healthy skin, were cultured and subcutaneously engrafted into immunodeficient mice. Cell infiltration and angiogenesis were analyzed in the grafts by immunohistochemical studies. The role of vascular endothelial growth factor (VEGF), CXCL12, and hypoxia‐inducible transcription factor 1α (HIF‐1α) in these processes was investigated using specific antagonists or small interfering RNA (siRNA)–mediated down‐regulation of HIF‐1α in fibroblasts.ResultsInflammatory (OA and RA) synovial fibroblasts, compared with healthy dermal or synovial tissue fibroblasts, induced a significant enhancement in myeloid cell infiltration and angiogenesis in immunodeficient mice. These activities were associated with increased constitutive and hypoxia‐induced expression of VEGF, but not CXCL12, in inflammatory fibroblasts compared with healthy fibroblasts. VEGF and CXCL12 antagonists significantly reduced myeloid cell infiltration and angiogenesis. Furthermore, targeting of HIF‐1α expression by siRNA or of HIF‐1α transcriptional activity by the small molecule chetomin in RA fibroblasts significantly reduced both responses.ConclusionThese results demonstrate that chronic synovial inflammation is associated with stable fibroblast changes that, under hypoxic conditions, are sufficient to induce inflammatory cell recruitment and angiogenesis, both of which are processes relevant to the perpetuation of chronic inflammation.
Prognostic factors in nonoperative therapy for chronic symptomatic calcific tendinitis of the shoulder
Authors: Ogon P. , Suedkamp N. P. , Jaeger M. , Izadpanah K. , Koestler W. , Maier D. 
Published: September 2009

AbstractObjectiveTo define prognostic factors in chronically symptomatic patients with calcific tendinitis of the shoulder.MethodsWe evaluated 420 patients (488 shoulders) in the context of a prospective cohort study. Epidemiologic data were assessed. The radiographic and sonographic appearance of the calcific deposits was classified. The mean period of nonoperative therapy was 4.4 years (range 0.5–13.7 years). After referral to our institution, standardized nonoperative therapy was continued for a minimum of 3 months. Failure of nonoperative therapy was defined as the persistence of symptomatic calcific tendinitis of the shoulder after a minimum of 6 months. Prognostic factors (determined at P < 0.05 by chi‐square test) were analyzed by logistic regression.ResultsOf the 420 patients, 269 (64%) were women, 151 (36%) were men. The mean age of the patients was 51.3 years (range 28–84 years). Occurrence of calcific tendinitis of the shoulder was unilateral in 84% and bilateral in 16%. Gärtner type I calcific deposits were found in 37%, type II in 32%, and type III in 31%. Failure of nonoperative therapy was observed in 114 patients (27%). Negative prognostic factors were bilateral occurrence of calcific tendinitis of the shoulder, localization to the anterior portion of the acromion, medial (subacromial) extension, and high volume of the calcific deposit. Positive prognostic factors were a Gärtner type III deposit and a lack of sonographic sound extinction of the calcific deposit.ConclusionOur findings demonstrate the existence of prognostic factors in the nonoperative treatment of chronic symptomatic calcific tendinitis of the shoulder. Guidelines for optimal treatment can be implemented according to these factors to avoid a long‐term symptomatic disease course.
18F‐fluorodeoxyglucose–positron emission tomography scanning is more useful in followup than in the initial assessment of patients with Erdheim‐Chester disease
Authors: Arnaud Laurent , Malek Zoulikha , Archambaud Frédérique , Kas Aurélie , Toledano Dan , Drier Aurélie , Zeitoun Delphine , Cluzel Philippe , Grenier Philippe A. , Chiras Jacques , Piette Jean‐Charles , Amoura Zahir , Haroche Julien 
Published: September 2009

AbstractObjectiveErdheim‐Chester disease (ECD) is a rare form of non–Langerhans' cell histiocytosis. The aim of this study was to assess the value of whole‐body scanning with 18F‐fluorodeoxyglucose–positron emission tomography (FDG‐PET) in a large cohort of ECD patients from a single center.MethodsWe retrospectively reviewed all PET scans performed on 31 patients with ECD who were referred to our department between 2005 and 2008. PET images were reviewed by 2 independent nuclear medicine specialist physicians and were compared with other imaging modalities performed within 15 days of each PET scan.ResultsThirty‐one patients (10 women and 21 men; median age 59.5 years) underwent a total of 65 PET scans. Twenty‐three patients (74%) were untreated at the time of the initial PET scan, whereas 30 of the 34 followup PET scans (88%) were performed in patients who were undergoing immunomodulatory therapy. Comparison of the initial and followup PET scans with other imaging modalities revealed that the sensitivity of PET scanning varied greatly among the different organs studied (range 4.3–100%), while the specificity remained high (range 69.2–100%). Followup PET scans were particularly helpful in assessing central nervous system (CNS) involvement, since the PET scan was able to detect an early therapeutic response of CNS lesions, even before magnetic resonance imaging showed a decrease in their size. PET scanning was also very helpful in evaluating the cardiovascular system, which is a major prognostic factor in ECD, by assessing the heart and the entire vascular tree during a single session.ConclusionThe results of our large, single‐center, retrospective study suggest that the findings of a FDG‐PET scan may be interesting in the initial assessment of patients with ECD, but its greater contribution is in followup of these patients.