bluuebunny/crossref_metadata_2025_split huggingface dataset:
Attachment of Osteocyte Cell Processes to the Bone Matrix
Authors: McNamara L.M. , Majeska R.J. , Weinbaum S. , Friedrich V. , Schaffler M.B. 
Published: February 2009

AbstractIn order for osteocytes to perceive mechanical information and regulate bone remodeling accordingly they must be anchored to their extracellular matrix (ECM). To date the nature of this attachment is not understood. Osteocytes are embedded in mineralized bone matrix, but maintain a pericellular space (50–80 nm) to facilitate fluid flow and transport of metabolites. This provides a spatial limit for their attachment to bone matrix. Integrins are cell adhesion proteins that may play a role in osteocyte attachment. However, integrin attachments require proximity between the ECM, cell membrane, and cytoskeleton, which conflicts with the osteocytes requirement for a pericellular fluid space. In this study, we hypothesize that the challenge for osteocytes to attach to surrounding bone matrix, while also maintaining fluid‐filled pericellular space, requires different “engineering” solutions than in other tissues that are not similarly constrained. Using novel rapid fixation techniques, to improve cell membrane and matrix protein preservation, and transmission electron microscopy, the attachment of osteocyte processes to their canalicular boundaries are quantified. We report that the canalicular wall is wave‐like with periodic conical protrusions extending into the pericellular space. By immunohistochemistry we identify that the integrin αvβ3 may play a role in attachment at these complexes; a punctate pattern of staining of β3 along the canalicular wall was consistent with observations of periodic protrusions extending into the pericellular space. We propose that during osteocyte attachment the pericellular space is periodically interrupted by underlying collagen fibrils that attach directly to the cell process membrane via integrin‐attachments. Anat Rec, 292:355–363, 2009. © 2009 Wiley‐Liss, Inc.
Expressing pain and fatigue: A new method of analysis to explore differences in osteoarthritis experience
Authors: Gooberman‐Hill Rachael , French Melissa , Dieppe Paul , Hawker Gillian 
Published: February 2009

AbstractObjectiveTo apply a new method of analysis to 2 large qualitative datasets in order to examine differences in osteoarthritis (OA) experience according to the affected joint (knee or hip) and sex.MethodsA secondary analysis of qualitative data from 2 studies was conducted. Study 1 comprised 28 focus groups with 50 men and 80 women (ages 47–92 years). Study 2 comprised 14 focus groups with 32 men and 56 women (ages 56–91 years). All participants had symptomatic OA. In Study 1, secondary analysis using comparative keyword analysis (CKA) compared relative frequencies of words uttered by participants experiencing knee pain with words used by participants experiencing hip pain. In Study 2, CKA compared words used by men with words used by women. Subsequent analysis explored the contexts in which participants used key words.ResultsAll participants in Study 1 described concerns with their bodies, activity limitations, and pain management, but details of their concerns differed. People with knee pain focused on stairs, weight, and stiffness, while those with hip pain were concerned with sidedness and groin pain. In Study 2, both men and women discussed activity and interaction with spouses. However, men used more factual words, especially relating to enumeration, while women offered more explanation without prompting from others.ConclusionCKA provides productive inroads into qualitative datasets. Understanding the different ways that affected joints are discussed, and sex differences in descriptions of OA, may lead to improvements in clinical assessment tools, better targeting of interventions, and enhanced communication between health care professionals and patients.
Perception of improvement in patients with rheumatoid arthritis varies with disease activity levels at baseline
Authors: Aletaha D. , Funovits J. , Ward M. M. , Smolen J. S. , Kvien T. K. 
Published: February 2009

AbstractObjectiveTo analyze the minimum clinically important improvement (MCII) of disease activity measures in rheumatoid arthritis (RA) using patient‐derived anchors, and to assess whether criteria for improvement differ with baseline disease activity.MethodsWe used data from a Norwegian observational database comprising 1,050 patients (73% women, 65% rheumatoid factor‐positive, mean duration of RA 7.7 years). At 3 months after initiation of therapy, patients indicated whether their condition had improved, had considerably improved, was unchanged, had worsened, or had considerably worsened. We used receiver operating characteristic curve analysis to determine the MCII for the Disease Activity Score based on the assessment of 28 joints (DAS28), the Simplified Disease Activity Index (SDAI), and the Clinical Disease Activity Index (CDAI), and analyzed the effects of different levels of baseline disease activity on the MCII.ResultsOn average, patients started with high disease activity and improved significantly during treatment (American College of Rheumatology 20%, 50%, and 70% improvement criteria responses were 37%, 17%, and 5%, respectively). The overall mean (95% confidence interval [95% CI]) thresholds for MCII after 3 months for the DAS28, SDAI, and CDAI were 1.20 (95% CI 1.18–1.22), 10.95 (95% CI 10.69–11.20), and 10.76 (95% CI 10.49–11.04), respectively, and the mean (95% CI) thresholds for major responses were 1.82 (95% CI 1.80–1.83), 15.82 (95% CI 15.65–16.00), and 15.00 (95% CI 14.82–15.18), respectively. With increasing disease activity, much higher changes in disease activity were needed to achieve MCII according to patient judgment.ConclusionThe perception of improvement of disease activity of patients with RA is considerably different depending on the disease activity level at which they start.
Pneumocystis jiroveci pneumonia in patients with rheumatoid arthritis treated with infliximab: A retrospective review and case–control study of 21 patients
Authors: Komano Yukiko , Harigai Masayoshi , Koike Ryuji , Sugiyama Haruhito , Ogawa Jun , Saito Kazuyoshi , Sekiguchi Naoya , Inoo Masayuki , Onishi Ikuko , Ohashi Hiroyuki , Amamoto Fujio , Miyata Masayuki , Ohtsubo Hideo , Hiramatsu Kazuko , Iwamoto Masahiro , Minota Seiji , Matsuoka Naoki , Kageyama Goichi , Imaizumi Kazuyoshi , Tokuda Hitoshi , Okochi Yasumi , Kudo Koichiro , Tanaka Yoshiya , Takeuchi Tsutomu , Miyasaka Nobuyuki 
Published: February 2009

AbstractObjectiveTo establish proper management of Pneumocystis jiroveci pneumonia (PCP) in rheumatoid arthritis (RA) patients treated with infliximab. PCP has been observed in 0.4% of patients with RA treated with infliximab in Japan.MethodsData from patients with RA (n = 21) who were diagnosed with PCP during infliximab treatment and from 102 patients with RA who did not develop PCP during infliximab therapy were collected from 14 rheumatology referral centers in Japan. A retrospective review of these patients and a case–control study to compare patients with and without PCP were performed.ResultsThe median length of time from the first infliximab infusion to the development of PCP was 8.5 weeks. At the onset of PCP, the median dosages of prednisolone and methotrexate were 7.5 mg/day and 8 mg/week, respectively. Pneumocystis jiroveci was microscopically identified in only 2 patients, although the polymerase chain reaction test for the organism was positive in 20 patients. The patients with PCP had significantly lower serum albumin levels (P < 0.001) and lower serum IgG levels (P < 0.001) than the patients without PCP. Computed tomography of the chest in all patients with PCP revealed ground‐glass opacity either with sharp demarcation by interlobular septa or without interlobular septal boundaries. Sixteen of the 21 patients with PCP developed acute respiratory failure, but all survived.ConclusionPCP is a serious complication that may occur early in the course of infliximab therapy in patients with RA. For the proper clinical management of this infectious disease, physicians need to be aware of the possibility of PCP developing during infliximab therapy.
Developmental and osteoarthritic changes in Col6a1‐knockout mice: Biomechanics of type VI collagen in the cartilage pericellular matrix
Authors: Alexopoulos Leonidas G. , Youn Inchan , Bonaldo Paolo , Guilak Farshid 
Published: February 2009

AbstractObjectiveChondrocytes, the sole cell type in articular cartilage, maintain the extracellular matrix (ECM) through a homeostatic balance of anabolic and catabolic activities that are influenced by genetic factors, soluble mediators, and biophysical factors such as mechanical stress. Chondrocytes are encapsulated by a narrow tissue region termed the “pericellular matrix” (PCM), which in normal cartilage is defined by the exclusive presence of type VI collagen. Because the PCM completely surrounds each cell, it has been hypothesized that it serves as a filter or transducer for biochemical and/or biomechanical signals from the cartilage ECM. The present study was undertaken to investigate whether lack of type VI collagen may affect the development and biomechanical function of the PCM and alter the mechanical environment of chondrocytes during joint loading.MethodsCol6a1−/− mice, which lack type VI collagen in their organs, were generated for use in these studies. At ages 1, 3, 6, and 11 months, bone mineral density (BMD) was measured, and osteoarthritic (OA) and developmental changes in the femoral head were evaluated histomorphometrically. Mechanical properties of articular cartilage from the hip joints of 1‐month‐old Col6a1−/−, Col6a1+/−, and Col6a1+/+ mice were assessed using an electromechanical test system, and mechanical properties of the PCM were measured using the micropipette aspiration technique.ResultsIn Col6a1−/− and Col6a1+/− mice the PCM was structurally intact, but exhibited significantly reduced mechanical properties as compared with wild‐type controls. With age, Col6a1−/− mice showed accelerated development of OA joint degeneration, as well as other musculoskeletal abnormalities such as delayed secondary ossification and reduced BMD.ConclusionThese findings suggest that type VI collagen has an important role in regulating the physiology of the synovial joint and provide indirect evidence that alterations in the mechanical environment of chondrocytes, due to either loss of PCM properties or Col6a1−/−‐derived joint laxity, can lead to progression of OA.
Triggering of proteinase‐activated receptor 4 leads to joint pain and inflammation in mice
Authors: McDougall Jason J. , Zhang Chunfen , Cellars Laurie , Joubert Eva , Dixon Chantelle M. , Vergnolle Nathalie 
Published: February 2009

AbstractObjectiveTo investigate the role of proteinase‐activated receptor 4 (PAR‐4) in mediating joint inflammation and pain in mice.MethodsKnee joint blood flow, edema, and pain sensitivity (as induced by thermal and mechanical stimuli) were assessed in C57BL/6 mice following intraarticular injection of either the selective PAR‐4 agonist AYPGKF‐NH2 or the inactive control peptide YAPGKF‐NH2. The mechanism of action of AYPGKF‐NH2 was examined by pretreatment of each mouse with either the PAR‐4 antagonist pepducin P4pal‐10 or the bradykinin antagonist HOE 140. Finally, the role of PAR‐4 in mediating joint inflammation was tested by pretreating mice with acutely inflamed knees with pepducin P4pal‐10.ResultsPAR‐4 activation caused a long‐lasting increase in joint blood flow and edema formation, which was not seen following injection of the control peptide. The PAR‐4–activating peptide was also found to be pronociceptive in the joint, where it enhanced sensitivity to a noxious thermal stimulus and caused mechanical allodynia and hyperalgesia. The proinflammatory and pronociceptive effects of AYPGKF‐NH2 could be inhibited by pepducin P4pal‐10 and HOE 140. Finally, pepducin P4pal‐10 ameliorated the clinical and physiologic signs of acute joint inflammation.ConclusionThis study demonstrates that local activation of PAR‐4 leads to proinflammatory changes in the knee joint that are dependent on the kallikrein–kinin system. We also show for the first time that PARs are involved in the modulation of joint pain, with PAR‐4 being pronociceptive in this tissue. Thus, blockade of articular PAR‐4 may be a useful means of controlling joint inflammation and pain.
Stromal cell–derived factor 1/CXCR4 signaling is critical for the recruitment of mesenchymal stem cells to the fracture site during skeletal repair in a mouse model
Authors: Kitaori Toshiyuki , Ito Hiromu , Schwarz Edward M. , Tsutsumi Ryosuke , Yoshitomi Hiroyuki , Oishi Shinya , Nakano Masakazu , Fujii Nobutaka , Nagasawa Takashi , Nakamura Takashi 
Published: February 2009

AbstractObjectiveStromal cell–derived factor 1 (SDF‐1; CXCL12/pre–B cell growth‐stimulating factor) is a dominant chemokine in bone marrow and is known to be involved in inflammatory diseases, including rheumatoid arthritis. However, its role in bone repair remains unknown. The purpose of this study was to investigate the role of SDF‐1 and its receptor, CXCR4, in bone healing.MethodsThe expression of SDF‐1 during the repair of a murine structural femoral bone graft was examined by real‐time polymerase chain reaction and immunohistochemical analysis. The bone graft model was treated with anti–SDF‐1 neutralizing antibody or TF14016, an antagonist for CXCR4, and evaluated by histomorphometry. The functional effect of SDF‐1 on primary mesenchymal stem cells was determined by in vitro and in vivo migration assays. New bone formation in an exchanging‐graft model was compared with that in the autograft models, using mice partially lacking SDF‐1 (SDF‐1+/−) or CXCR4 (CXCR4+/−).ResultsThe expression of SDF1 messenger RNA was increased during the healing of live bone grafts but was not increased in dead grafts. High expression of SDF‐1 protein was observed in the periosteum of the live graft. New bone formation was inhibited by the administration of anti–SDF‐1 antibody or TF14016. SDF‐1 increased mesenchymal stem cell chemotaxis in vitro in a dose‐dependent manner. The in vivo migration study demonstrated that mesenchymal stem cells recruited by SDF‐1 participate in endochondral bone repair. Bone formation was decreased in SDF‐1+/− and CXCR4+/− mice and was restored by the graft bones from CXCR4+/− mice transplanted into the SDF‐1+/− femur, but not vice versa.ConclusionSDF‐1 is induced in the periosteum of injured bone and promotes endochondral bone repair by recruiting mesenchymal stem cells to the site of injury.
Scleroderma prevalence: Demographic variations in a population‐based sample
Authors: Bernatsky S. , Joseph L. , Pineau C. A. , Belisle P. , Hudson M. , Clarke A. E. 
Published: February 2009

AbstractObjectiveTo estimate the prevalence of systemic sclerosis (SSc) using population‐based administrative data, and to assess the sensitivity of case ascertainment approaches.MethodsWe ascertained SSc cases from Quebec physician billing and hospitalization databases (covering ∼7.5 million individuals). Three case definition algorithms were compared, and statistical methods accounting for imperfect case ascertainment were used to estimate SSc prevalence and case ascertainment sensitivity. A hierarchical Bayesian latent class regression model that accounted for possible between‐test dependence conditional on disease status estimated the effect of patient characteristics on SSc prevalence and the sensitivity of the 3 ascertainment algorithms.ResultsAccounting for error inherent in both the billing and the hospitalization data, we estimated SSc prevalence in 2003 at 74.4 cases per 100,000 women (95% credible interval [95% CrI] 69.3–79.7) and 13.3 cases per 100,000 men (95% CrI 11.1–16.1). Prevalence was higher for older individuals, particularly in urban women (161.2 cases per 100,000, 95% CrI 148.6–175.0). Prevalence was lowest in young men (in rural areas, as low as 2.8 cases per 100,000, 95% CrI 1.4–4.8). In general, no single algorithm was very sensitive, with point estimates for sensitivity ranging from 20–73%.ConclusionWe found marked differences in SSc prevalence according to age, sex, and region. In general, no single case ascertainment approach was very sensitive for SSc. Therefore, using data from multiple sources, with adjustment for the imperfect nature of each, is an important strategy in population‐based studies of SSc and similar conditions.
Work disability in systemic lupus erythematosus
Authors: Dhanhani Ali M. Al , Gignac Monique A. M. , Su Jiandong , Fortin Paul R. 
Published: February 2009

AbstractObjectiveTo determine the prevalence, accrual over time, and risk factors of work disability in patients with systemic lupus erythematosus (SLE).MethodsWe studied 432 patients from an inception cohort. Work disability was measured from a single self‐report question. Data were prospectively collected and included sociodemographic information, clinical lupus features including activity (Systemic Lupus Erythematosus Disease Activity Index 2000 update [SLEDAI‐2K]), damage (Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index), and organ involvement, as well as health status (Short Form 36 [SF‐36]), comorbidity, and medication use. Student's t‐test and Wilcoxon's rank sum test were used to compare continuous variables and chi‐square tests were used for dichotomous variables. Descriptive survival curves of time to work disability were presented. Bivariate and multivariate logistic regressions were used to describe the relationships between clinically relevant factors and work disability.ResultsOf 432 patients, 88% were women and 73% were white. Within the first year of diagnosis, 47% of patients were employed, 7% had a disability, and 7% were on sick leave. Overall, work disability was found in 98 (23%) patients. Risk factors for work disability found in the multivariate regression analysis were younger age at diagnosis, less education, fibromyalgia, hypertension, higher first‐visit SLEDAI‐2K score, and lower first‐visit SF‐36 score.ConclusionWork disability is frequent in patients with SLE, with a cumulative prevalence of 23%. Work disability was associated with a complex array of health factors, including comorbidity, physical and mental health limitations, and clinical features of lupus, that warrant increased attention in future research.
Meniscal tear in knees without surgery and the development of radiographic osteoarthritis among middle‐aged and elderly persons: The multicenter osteoarthritis study
Authors: Englund Martin , Guermazi Ali , Roemer Frank W. , Aliabadi Piran , Yang Mei , Lewis Cora E. , Torner James , Nevitt Michael C. , Sack Burton , Felson David T. 
Published: February 2009

AbstractObjectiveAlthough partial meniscectomy is a risk factor for the development of knee osteoarthritis (OA), there is a lack of evidence that meniscal damage that is not treated with surgery would also lead to OA, suggesting that surgery itself may cause joint damage. Furthermore, meniscal damage is common. The aim of this study was to evaluate the association between meniscal damage in knees without surgery and the development of radiographic tibiofemoral OA.MethodsWe conducted a prospective case–control study nested within the observational Multicenter Osteoarthritis Study, which included a sample of men and women ages 50–79 years at high risk of knee OA who were recruited from the community. Patients who had no baseline radiographic knee OA but in whom tibiofemoral OA developed during the 30‐month followup period were cases (n = 121). Control subjects (n = 294) were drawn randomly from the same source population as cases but had no knee OA after 30 months of followup. Individuals whose knees had previously undergone surgery were excluded. Meniscal damage was defined as the presence of any medial or lateral meniscal tearing, maceration, or destruction.ResultsMeniscal damage at baseline was more common in case knees than in control knees (54% versus 18%; P < 0.001). The model comparing any meniscal damage with no meniscal damage (adjusted for baseline age, sex, body mass index, physical activity, and mechanical knee alignment) yielded an odds ratio of 5.7 (95% confidence interval 3.4–9.4).ConclusionIn knees without surgery, meniscal damage is a potent risk factor for the development of radiographic OA. These results highlight the need for better understanding, prevention, and treatment of meniscal damage.
Disease control and health‐related quality of life in juvenile idiopathic arthritis
Authors: Seid Michael , Opipari Lisa , Huang Bin , Brunner Hermine I. , Lovell Daniel J. 
Published: February 2009

AbstractObjectiveTo examine variability in health‐related quality of life (HRQOL) in children with juvenile idiopathic arthritis (JIA) experiencing no or minimal clinical symptoms, and in a subgroup with polyarticular JIA treated with biologic agents for 12 months.MethodsWe defined 3 samples using a database of patients ages 2–18 years with JIA (n = 524; patient visits [PV] = 2,354): visits (PV = 2,155) with no or minimal clinical symptoms on at least 1 of 4 measures (active joint count, pain, physician global disease rating, Childhood Health Assessment Questionnaire); visits (PV = 941) with no or minimal symptoms on all 4 measures; and children (n = 31) with polyarticular JIA treated with biologic agents for 12 months. HRQOL was measured using the Pediatric Quality of Life Inventory (PedsQL) and the percentage of patients with suboptimal HRQOL was determined.ResultsIn PV with a PedsQL score, suboptimal HRQOL by self‐report occurred in 362 (20.6%) PV with at least 1 indicator of minimal symptoms, and in 64 (7.9%) PV with all 4 measures indicating minimal symptoms (519 [25.7%] and 95 [10.7%], respectively, by parent report). For children with polyarticular JIA treated for 12 months with biologic agents, 7 (25.9%) patients by self‐report and 10 (35.7%) patients by parent report were in the suboptimal range of HRQOL.ConclusionA substantial percentage of patients with JIA who report no or mild clinical symptoms experience suboptimal HRQOL. This is also true for patients with polyarticular JIA treated with biologic agents for 12 months. Although disease activity and clinical symptoms are related to HRQOL, considerable unexplained variation in HRQOL exists. HRQOL needs to be assessed independently regardless of clinical status.