bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of integrative cartilage repair by proteoglycan 4 in synovial fluid
Authors: Englert Carsten , McGowan Kevin B. , Klein Travis J. , Giurea Alexander , Schumacher Barbara L. , Sah Robert L. 
Published: April 2005

AbstractObjectiveTo determine the effects of the articular cartilage surface, as well as synovial fluid (SF) and its components, specifically proteoglycan 4 (PRG4) and hyaluronic acid (HA), on integrative cartilage repair in vitro.MethodsBlocks of calf articular cartilage were harvested, some with the articular surface intact and others without. Some of the latter types of blocks were pretreated with trypsin, and then with bovine serum albumin, SF, PRG4, or HA. Immunolocalization of PRG4 on cartilage surfaces was performed after treatment. Pairs of similarly treated cartilage blocks were incubated in partial apposition for 2 weeks in medium supplemented with serum and 3H‐proline. Following culture, mechanical integration between apposed cartilage blocks was assessed by measuring adhesive strength, and protein biosynthesis and deposition were determined by incorporated 3H‐proline.ResultsSamples with articular surfaces in apposition exhibited little integrative repair compared with samples with cut surfaces in apposition. PRG4 was immunolocalized at the articular cartilage surface, but not in deeper, cut surfaces (without treatment). Cartilage samples treated with trypsin and then with SF or PRG4 exhibited an inhibition of integrative repair and positive immunostaining for PRG4 at treated surfaces compared with normal cut cartilage samples, while samples treated with HA exhibited neither inhibited integrative repair nor PRG4 at the tissue surfaces. Deposition of newly synthesized protein was relatively similar under conditions in which integration differed significantly.ConclusionThese results support the concept that PRG4 in SF, which normally contributes to cartilage lubrication, can inhibit integrative cartilage repair. This has the desirable effect of preventing fusion of apposing surfaces of articulating cartilage, but has the undesirable effect of inhibiting integrative repair.
Prophylactic adenovirus‐mediated human kallistatin gene therapy suppresses rat arthritis by inhibiting angiogenesis and inflammation
Authors: Wang Chrong‐Reen , Chen Shih‐Yao , Wu Chao‐Liang , Liu Ming‐Fei , Jin Ying‐Tai , Chao Lee , Chao Julie 
Published: April 2005

AbstractObjectiveKallistatin has been shown to be an angiogenesis inhibitor. In this study, we investigated whether adenovirus‐mediated kallistatin gene delivery has a prophylactic effect in a rat arthritis model.MethodsAdenovirus containing the human kallistatin gene (AdHKBP) was injected intraarticularly into ankle joints before the onset of arthritis in a rat model. The effect of kallistatin gene transfer on endothelial cell proliferation in joint extracts was assayed. The response to kallistatin treatment was determined according to clinical parameters, including ankle circumference, articular index, and radiographic scores. Hematoxylin and eosin staining was performed in order to score joint tissues and count neutrophil numbers. In addition, small vessels were quantified by identification of von Willebrand factor–positive endothelial cells. The inflammatory responses were determined by measuring tumor necrosis factor α (TNFα) and interleukin‐1β (IL‐1β) levels in ankle homogenates.ResultsThe expression of recombinant human kallistatin in rat ankle joints after gene transfer was identified by immunohistochemical analysis and Western blotting. Significant reductions in the ankle circumference, articular index, and radiographic score were observed in AdHKBP‐treated rats compared with control rats treated with the adenoviral plasmid carrying green fluorescent protein. Kallistatin gene transfer also significantly ameliorated the histologic scores in ankle joints and reduced vessel density and neutrophil numbers. The inhibitory effect of kallistatin on the accumulation of inflammatory cells in ankle joints was accompanied by reduced TNFα and IL‐1β levels in joint homogenates. Furthermore, an in vitro experiment showed that the proliferation of endothelial cells was markedly inhibited by the addition of AdHKBP‐treated joint extract to the culture media, supporting a role of kallistatin in inhibiting angiogenesis.ConclusionThis study demonstrates that kallistatin gene therapy has a prophylactic effect in inhibiting arthritis in the rat ankle. Kallistatin inhibits arthritis through its antiangiogenesis and antiinflammation activities. These results implicate potential therapeutic applications for suppression of arthritis by kallistatin gene therapy.
Association of the frizzled‐related protein gene with symptomatic osteoarthritis at multiple sites
Authors: Min J. L. , Meulenbelt I. , Riyazi N. , Kloppenburg M. , Houwing‐Duistermaat J. J. , Seymour A. B. , Pols H. A. , van Duijn C. M. , Slagboom P. E. 
Published: April 2005

AbstractObjectiveTo confirm the association of 2 variants of the Frizzled‐related protein gene (FRZB) with osteoarthritis (OA) of the hip, and to investigate whether these variants also associate with other heritable generalized OA phenotypes.MethodsAn association analysis of 2 variants (R200W and R324G) of FRZB was performed in a random sample of 1,369 subjects (ages 55–70 years) from a population‐based cohort (the Rotterdam Study) scored for radiographic characteristics of OA in the hip, hand, spine, and knee and in a patient population of Caucasian probands (ages 40–70 years) and their siblings selected for the presence of primary symptomatic OA at multiple sites.ResultsThe allele frequency of the 2 variants was not significantly different between subjects with hip radiographic OA (ROA) and controls. The frequency of the G allele of the R324G variant was significantly increased in subjects with generalized ROA from the Rotterdam Study (0.10) and in subjects from the Genetics, osteoARthritis and Progression study (0.11) compared with that in controls from the Rotterdam Study (0.08). Carriers of this G allele had increased susceptibility for generalized ROA (odds ratio [OR] 1.4, 95% confidence interval [95% CI] 0.9–1.9, P = 0.10) or familial symptomatic OA at multiple sites (OR 1.6, 95% CI 1.1–2.3, P = 0.02).ConclusionOur results confirm that the R324G variant of the FRZB gene is involved in OA and indicate a role of this variant in several generalized OA phenotypes. A more extended OA phenotype may indeed be expected from genetic variation in an essential pathway of skeletal development such as Wnt signaling.
Bilateral subchondral insufficiency fracture of the femoral head after renal transplantation: A case report
Authors: Ikemura Satoshi , Yamamoto Takuaki , Nakashima Yasuharu , Shuto Toshihide , Jingushi Seiya , Iwamoto Yukihide 
Published: April 2005

AbstractThis report describes the case of a 47‐year‐old woman who was found to have subchondral insufficiency fractures in both femoral heads after renal transplantation. Initially, plain radiographs showed no obvious changes, but magnetic resonance imaging (MRI) revealed an irregular, discontinuous, low‐intensity band on the T1‐weighted image of both hips. The patient was treated nonsurgically. Ten months after onset, the pain in both hips disappeared, and plain radiographs and MRI showed no abnormalities. Subchondral insufficiency fracture should be considered in the diagnosis of patients who have hip pain after renal transplantation.
Association of Epstein‐Barr virus with systemic lupus erythematosus: Effect modification by race, age, and cytotoxic T lymphocyte–associated antigen 4 genotype
Authors: Parks Christine G. , Cooper Glinda S. , Hudson Lori L. , Dooley Mary Anne , Treadwell Edward L. , St.Clair E. W. , Gilkeson Gary S. , Pandey Janardan P. 
Published: April 2005

AbstractObjectiveEpstein‐Barr virus (EBV) is hypothesized to play a role in the development of systemic lupus erythematosus (SLE). Cytotoxic T lymphocyte–associated antigen 4 (CTLA‐4) is important in regulating T cell–mediated immunity, encompassing the first line of response to viral infections, and genetic variation in CTLA‐4 has been associated with SLE. This study examined the seroprevalence of EBV in a population‐based study of SLE patients from the southeastern United States, and potential interactions with CTLA‐4 polymorphisms were assessed.MethodsCases comprised 230 subjects recently diagnosed as having SLE (144 African American and 86 white) from university and community‐based clinics, and controls comprised 276 age‐, sex‐, and state‐matched subjects (72 African American and 204 white) recruited from driver's license registries. Antibodies to EBV capsid antigen were determined by enzyme‐linked immunosorbent assay, with results expressed as positive or negative using the international standardized ratio (ISR) (a ratio of the sample absorbance to a known standard). CTLA‐4 genotypes were identified by polymerase chain reaction–based methods.ResultsIn African Americans, EBV‐IgA seroprevalence was strongly associated with SLE (odds ratio [OR] 5.6, 95% confidence interval [95% CI] 3.0–10.6). In whites, the modest association of SLE with EBV‐IgA (OR 1.6) was modified by age, in that the strongest association was observed in those older than age 50 years (OR 4.1, 95% CI 1.6–10.4). The seroprevalence of EBV‐IgM and that of EBV‐IgG were not associated with SLE. Higher EBV‐IgG absorbance ratios were observed in SLE patients, with a significant dose response across units of the ISR in African Americans (P < 0.0001). Allelic variation in the CTLA‐4 gene promoter (−1661A/G) significantly modified the association between SLE and EBV‐IgA (P = 0.03), with a stronger association among those with the −1661AA genotype.ConclusionThese findings suggest that repeated or reactivated EBV infection, which results in increased EBV‐IgA seroprevalence and higher IgG antibody titers, may be associated with SLE, and that the CTLA‐4 genotype influences immune responsiveness to EBV in SLE patients. The observed patterns of effect modification by race, age, and CTLA‐4 genotype should be examined in other studies and may help frame new hypotheses regarding the role of EBV in SLE etiology.
Elevated expression of the Brn‐3a and Brn‐3b transcription factors in systemic lupus erythematosus correlates with antibodies to Brn‐3 and overexpression of Hsp90
Authors: Ripley B. J. M. , Rahman M. A. , Isenberg D. A. , Latchman D. S. 
Published: April 2005

AbstractObjectiveImportant developmental and antiapoptotic roles have been described for the Brn‐3 family of transcription factors in mammalian cells. Following a report of pathogenic autoantibody‐inducing T cell reactivity to the Brn‐3 transcription factors in murine lupus, we undertook this study to investigate serum levels of antibodies to Brn‐3 and levels of expression of Brn‐3 in peripheral blood mononuclear cells (PBMCs) of patients with systemic lupus erythematosus (SLE).MethodsSerum and PBMC samples were obtained from 87 SLE patients and 30 normal control subjects. Serum antibodies to the Brn‐3a and Brn‐3b transcription factors were measured by enzyme‐linked immunosorbent assay. Levels of Brn‐3a and Brn‐3b messenger RNA (mRNA) in PBMCs were measured by reverse transcription and real‐time quantitative polymerase chain reaction.ResultsElevated serum levels of antibodies to Brn‐3a and Brn‐3b were found in 43% and 32%, respectively, of SLE patients. This elevation paralleled enhanced expression of Brn‐3a and Brn‐3b in PBMCs of 44% and 31%, respectively, of SLE patients. Furthermore, we observed a significant correlation (P = 0.002) between elevated levels of anti–Brn‐3b antibodies and elevated levels of Brn‐3b mRNA in individual patients. A preliminary analysis of possible target genes for Brn‐3a and Brn‐3b revealed a significant correlation (P = 0.01) between the level of Brn‐3a mRNA and the level of Hsp90 protein (90‐kd heat‐shock protein, which is overexpressed in SLE) in PBMCs of SLE patients. In addition, we observed that overexpression of Brn‐3a and Brn‐3b in cultured cells enhanced expression of Hsp90 protein and transcription of Hsp90 promoter–reporter constructs. Finally, we observed an association between elevated levels of Brn‐3a mRNA and active SLE (P = 0.002).ConclusionExpression of both Brn‐3a and Brn‐3b was found to be enhanced in SLE, and this correlated with enhanced levels of autoantibodies to these proteins and with the previously reported overexpression of Hsp90, which was shown to be a novel gene regulated by Brn‐3a and Brn‐3b. The overexpression of Brn‐3a correlated with active disease, suggesting that it may play a role in the disease process via its targeting by the immune system and its ability to induce the expression of specific genes.
Anaerobic exercise capacity in patients with juvenile‐onset idiopathic inflammatory myopathies
Authors: Takken Tim , van der Net Janjaap , Helders Paul J. M. 
Published: April 2005

AbstractObjectiveTo 1) report the feasibility of an “all‐out” 30‐second cycling exercise test (Wingate Anaerobic Exercise Test [WAnT]) in juvenile‐onset idiopathic inflammatory myopathy (JIIM) patients, 2) describe the anaerobic exercise capacity in juvenile dermatomyositis patients, and 3) determine if the anaerobic exercise capacity could be related to disease duration or disease phase.MethodsTwenty patients (age 14.13 ± 5.4 years) with JIIM participated in this study. All patients were able to perform the WAnT without adverse events.ResultsComparison with healthy controls revealed a −29.3 ± 26.58% (P = 0.001) and −27.6 ± 25.7% (P = 0.002) impairment in mean power and peak power on the WAnT, respectively. The WAnT correlated with disease phase and with knee extensor muscle strength.ConclusionThe WAnT might be a valuable adjunct next to other assessment tools in the followup of JIIM patients.
Remitting seronegative symmetrical synovitis with pitting edema of the hands: Ultrasound, color doppler ultrasound, and magnetic resonance imaging findings
Authors: Klauser Andrea , Frauscher Ferdinand , Halpern Ethan J. , Mur Erich , Springer Peter , Judmaier Werner , Schirmer Michael 
Published: April 2005

AbstractObjectiveTo assess the value of gray‐scale ultrasound (US), color Doppler ultrasound (CDUS), contrast‐enhanced CDUS, and magnetic resonance imaging (MRI) in the diagnostic evaluation of the hands in patients with remitting seronegative symmetrical synovitis with pitting edema (RS3PE).MethodsEight patients (5 men, 3 women; mean ± SD age 69.3 ± 7.2 years) with clinical diagnosis of RS3PE syndrome underwent US, CDUS, contrast‐enhanced CDUS, and MRI. US was performed with a linear array transducer operating at 12 MHz. The US contrast agent (SHU 508; Levovist, Schering, Germany) was intravenously infused in a concentration of 300 mg/ml at a rate of 1 ml/minute.ResultsAll patients showed symmetric subcutaneous edema and synovitis of tendons and finger joints on both US and MRI. Vascularity was detected subcutaneously in tendon sheaths and in the joint synovia on CDUS and MRI. Detection of increased vascularity was improved after contrast administration compared with unenhanced CDUS (P < 0.01).ConclusionUltrasound, CDUS, contrast‐enhanced CDUS, and MRI are valuable tools in the diagnostic evaluation of involved anatomic structures in patients with RS3PE. Contrast‐enhanced CDUS is superior to CDUS in assessment of inflammatory edema, effusion, and synovitis.
History of infection before the onset of juvenile dermatomyositis: Results from the National Institute of Arthritis and Musculoskeletal and Skin Diseases Research Registry
Authors: Pachman Lauren M. , Lipton Rebecca , Ramsey‐Goldman Rosalind , Shamiyeh Eli , Abbott Kathy , Mendez Eduardo P. , Dyer Alan , Curdy Deborah Mc , Vogler Larry , Reed Ann , Cawkwell Gail , Zemel Lawrence , Sandborg Christy , Rivas‐Chacon Rafael , Hom Christine , Ilowite Norman , Gedalia Abraham , Gitlin Jonathan , Borzy Michael 
Published: April 2005

AbstractObjectiveTo obtain data concerning a history of infection occurring in the 3 months before recognition of the typical weakness and rash associated with juvenile dermatomyositis (JDM).MethodsParents or caretakers of children within 6 months of JDM diagnosis were interviewed by the registry study nurse concerning their child's symptoms, environment, family background, and illness history. Physician medical records were reviewed, confirming the JDM diagnosis.ResultsChildren for which both a parent interview and physician medical records at diagnosis were available (n = 286) were included. Diagnoses were as follows: definite/probable JDM (n = 234, 82%), possible JDM (n = 43, 15%), or rash only (n = 9, 3%). The group was predominantly white (71%) and had a girl:boy ratio of 2:1. Although the mean age at onset was 6.7 years for girls and 7.3 years for boys, 25% of the children were ≤4 years old at disease onset. In the 3 months before onset, 57% of the children had respiratory complaints, 30% had gastrointestinal symptoms, and 63% of children with these symptoms of infection were given antibiotics.ConclusionThis study provides evidence that JDM affects young children. The symptoms of the typical rash and weakness often follow a history of respiratory or gastrointestinal complaints. These data suggest that the response to an infectious process may be implicated in JDM disease pathogenesis.
Two major spondylarthropathy phenotypes are distinguished by pattern analysis in multiplex families
Authors: Porcher Raphaël , Said‐Nahal Roula , D'Agostino Maria‐Antonietta , Miceli‐Richard Corinne , Dougados Maxime , Breban Maxime 
Published: April 2005

AbstractObjectiveTo examine whether spondylarthropathy (SpA) disease manifestations would combine in any ordered pattern among patients from SpA multiplex families.MethodsSpA patients (n = 540) belonging to 190 multiplex families were thoroughly investigated. Clinical data was collected, systematic pelvic radiographs were taken, and HLA–B27 status was determined. The patterns of SpA manifestations were examined by several methods, including multiple correspondence analysis, nonhierarchical and hierarchical clustering, and discriminant analysis.ResultsThe nonhierarchical cluster analysis allowed us to classify patients, independent of disease duration, into 2 major groups of comparable size. Group A contained a majority of the women, whereas group B predominantly consisted of men. The 2 groups were very similar regarding axial symptoms, radiographic sacroiliitis, and uveitis. Group B was characterized by a younger age at onset and a higher frequency of clinical enthesitis, peripheral arthritis, dactylitis, psoriasis, and inflammatory bowel disease than group A. Patients belonging to those groups exhibited some degree of familial aggregation, thereby supporting their intrinsic validity.ConclusionPattern analysis of SpA manifestations among familial SpA allowed us to recognize 2 main clusters independent of disease duration. Furthermore, there was a trend toward aggregation by cluster among families, suggesting that they are determined by specific genetic factors. These clusters may indeed correspond to different severity patterns.
Risk factors for visual loss in an Italian population‐based cohort of patients with giant cell arteritis
Authors: Salvarani Carlo , Cimino Luca , Macchioni Pierluigi , Consonni Dario , Cantini Fabrizio , Bajocchi Gianluigi , Pipitone Nicolò , Catanoso Maria Grazia , Boiardi Luigi 
Published: April 2005

AbstractObjectiveTo evaluate the frequency of visual manifestations at presentation in an Italian population‐based cohort of patients with biopsy‐proven giant cell arteritis (GCA), and to investigate predictors for the development of permanent visual loss.MethodsWe identified 136 Reggio Emilia (Italy) residents with biopsy‐proven GCA diagnosed between 1986 and 2002. Medical records of these 136 patients were reviewed, and demographic, clinical, and laboratory data were collected.Multivariate analysis with multiple logistic regression models was performed to identify the best predictors of visual loss.ResultsVisual manifestations developed in 41 patients (30.1%). Partial or total visual loss was observed in 26 patients (19.1%). Anterior ischemic optic neuropathy was seen in 24 patients, and 2 patients had central retinal artery occlusion. Unilateral vision loss occurred in 19 patients, and bilateral visual loss in 7. In 25 patients, visual loss developed before glucocorticoid therapy for GCA was started. The age at disease onset was significantly higher in patients with permanent visual loss compared with those without it. The frequency of systemic signs/symptoms and erythrocyte sedimentation rate (ESR) and C‐reactive protein values at diagnosis were significantly lower in patients with permanent visual loss. By multivariate logistic regression, the only statistically significant predictor for the development of permanent visual loss was the absence of high levels of ESR at diagnosis (tertile 2: Odds ratio [OR] 0.08; tertile 3: OR 0.11). Other predictors included in the model were the absence of systemic manifestations (OR 0.24), an older age at disease diagnosis (quintile 5: OR 5.60), and the presence of an elevated platelet count at diagnosis (OR 4.99), however they were only of borderline statistical significance.ConclusionThe proportion of Italian patients with GCA that developed visual loss was similar to that reported from other countries. The patients with low inflammatory response had a higher risk of visual loss.
Clinical academic rheumatology: Getting more than you pay for
Authors: Wickersham Pendleton , Golz Diane , West Sterling G. 
Published: April 2005

AbstractObjectiveRheumatology is among the least compensated specialties in medicine today. This is a significant problem for clinical rheumatologists in academic medicine who are often expected to earn their salaries through clinical practice alone. Additionally, academic rheumatologists usually cannot generate revenue through office laboratory monitoring, radiographs, or bone densitometry to supplement their income (i.e., downstream income). The purpose of our study was to examine revenue generated from downstream income to a university by a clinical‐academic rheumatologist.MethodsConsecutive outpatients (n = 127) seen predominately by one academic rheumatologist over one month of clinic were followed for 18 months. The total physician compensation for patient visits was calculated and compared with the revenue generated from laboratory tests, radiologic studies, consultations, and specific rheumatologic treatments and procedures performed or ordered. Medicare reimbursement rates for 2003 were used as compensation standards for all charges.ResultsPhysician office visit billing generated $36,297 from 730 office visits. The total amount of downstream income from these office visits was $363,813 ($47,386 from laboratory tests, $35,582 from radiologic studies, $8,159 from rheumatologic procedures, $261,584 from rheumatologic infusions, and $11,101 from initial consultations). Therefore, $10.02 of downstream revenue was generated for every $1.00 of office visit compensation applied to the academic rheumatologist's salary.ConclusionAlthough academic rheumatologists struggle to bill their salaries through seeing more patients, they are clearly a bargain for a university hospital because they generate >$10.00 for every $1.00 they receive for an office visit.