bluuebunny/crossref_metadata_2025_split huggingface dataset:
Morphometric analysis of the uterine endometrium of swine on days 12 and 16 postestrus
Authors: Blackwell Dianna M. , Speth Robert C. , Mirando Mark A. 
Published: December 2002

AbstractThe uterine endometrium of swine is comprised of luminal epithelial, glandular epithelial, and stromal cells that secrete the luteolysin, prostaglandin F2α (PGF2α), during late diestrus. However, which of these cells contribute the most to luteolytic PGF2α secretion is unknown because the cellular composition of the endometrium has not been quantified. Therefore, this study quantified the cellular composition of the endometrium on days 12 and 16 postestrus by histologic and morphometric analyses. On day 12, the endometrium consisted predominantly of stromal cells (47% of total cell quantity) and glandular epithelial cells (37%), whereas luminal epithelial cells represented only 16% of the total of the three cell types. The number of glandular epithelial cells tended to increase (P < 0.10) between days 12 and 16, such that they comprised 45% of the endometrium by day 16, while the number of stromal and luminal cells did not change and accounted for 45% and 10% of the cells, respectively. Luminal epithelial cells had a 58% greater cross‐sectional area (P < 0.001) than glandular epithelial cells, whereas glandular epithelial cells had a 22% greater area (P < 0.001) than stromal cells. Glandular epithelial cells decreased (P < 0.001) in cross‐sectional area between days 12 and 16, whereas the area of luminal epithelial and stromal cells remained unchanged. These results indicate that the porcine endometrium is comprised predominantly of stromal and glandular epithelial cells that are likely to contribute substantially to endometrial PGF2α secretion during luteolysis. The contribution of glandular epithelium to luteolytic PGF2α secretion probably increases during diestrus as the number of these cells increases. Anat Rec Part A 270A:59–66, 2003. © 2003 Wiley‐Liss, Inc.
Management of glucocorticoid‐induced osteoporosis in patients with rheumatoid arthritis: Rates and predictors of care in an academic rheumatology practice
Authors: Solomon Daniel H. , Katz Jeffrey N. , Jacobs Jonathan P. , La Tourette Alison M. , Coblyn Jonathan 
Published: December 2002

AbstractObjectiveTo examine rheumatologists' management practices for patients with rheumatoid arthritis (RA) taking glucocorticoids seen at one academic medical rheumatology practice.MethodsAll patients diagnosed with RA making at least 2 visits to the practice who were noted to be taking glucocorticoids on an index visit in January or February 1999 were included in a retrospective chart review.ResultsOf the 623 eligible patients identified with RA, 236 patients were taking glucocorticoids at their index visit and were included in this study. The mean daily dosage of prednisone (or its equivalent) was 8.8 mg and the mean duration of use during the 2‐year chart review was 15.4 months. Twenty‐three percent of the study population underwent bone densitometry, and 42% were prescribed a medication that reduces bone loss (not including calcium and/or vitamin D). Calcium and/or vitamin D were noted on the medication lists of 25% of patients. Factors associated with not undergoing bone densitometry in adjusted logistic models included male patient sex and premenopausal status in women. No physician factors were significantly related to performing bone densitometry. Variables associated with not receiving prescription treatment of osteoporosis were male patient sex, premenopausal status, and having at least 1 comorbid condition.ConclusionPatients with RA taking oral glucocorticoids did not routinely undergo bone densitometry and/or receive prescription medications for osteoporosis. Men and premenopausal women were less likely to undergo bone densitometry and to receive a prescription medication for osteoporosis than postmenopausal women. Interventions to improve detection and prevention of glucocorticoid‐induced osteoporosis are necessary.
Therapeutic benefit of blocking interleukin‐6 activity with an anti–interleukin‐6 receptor monoclonal antibody in rheumatoid arthritis: A randomized, double‐blind, placebo‐controlled, dose‐escalation trial
Authors: Choy E. H. S. , Isenberg D. A. , Garrood T. , Farrow S. , Ioannou Y. , Bird H. , Cheung N. , Williams B. , Hazleman B. , Price R. , Yoshizaki K. , Nishimoto N. , Kishimoto T. , Panayi G. S. 
Published: December 2002

AbstractObjectiveTo investigate the safety and efficacy of MRA, a recombinant human anti–interleukin‐6 (anti–IL‐6) receptor monoclonal antibody of the IgG1 subclass that inhibits the function of IL‐6, in patients with established rheumatoid arthritis (RA).MethodsA randomized, double‐blind, placebo‐controlled, dose‐escalation trial was conducted in 45 patients with active RA, as defined by the American College of Rheumatology (ACR) revised criteria. Patients were sequentially allocated to receive a single intravenous dose of either 0.1, 1, 5, or 10 mg/kg of MRA or placebo. The primary efficacy end point was meeting the ACR 20% response criteria at week 2 after treatment.ResultsDemographic features were similar between treatment groups. At week 2, a significant treatment difference was observed between the 5 mg/kg of MRA and placebo, with 5 patients (55.6%) in the MRA cohort and none in the placebo cohort achieving ACR 20% improvement. There was no statistically significant difference in the ACR 20% response between the other 3 MRA cohorts and placebo at week 2. The mean disease activity score at week 2 in those who received 5 mg/kg and 10 mg/kg of MRA was 4.8 and 4.7 (P < 0.001 and P < 0.001 by analysis of variance), respectively. These mean scores were statistically significantly lower than those in the 0.1‐ and 1‐mg/kg MRA and the placebo cohorts (6.4, 6.2, and 7.0, respectively). The erythrocyte sedimentation rate and C‐reactive protein values fell significantly in the 5‐ and 10‐mg/kg MRA cohorts and normalized 2 weeks after treatment. Seventeen patients (5, 4, 6, 2, and 0 patients in the placebo, 0.1‐, 1‐, 5‐, and 10‐mg/kg MRA cohorts, respectively) required corticosteroid or disease‐modifying antirheumatic drug treatment because of active disease before study end. They were regarded as nonresponders from the time they received these treatments. Diarrhea was the most common adverse event, occurring in 8% of patients. Seven patients (15.6%) reported a severe adverse event (3, 1, 2, and 2 patients in the placebo, 0.1‐, 1‐, and 10‐mg/kg MRA cohorts). There were no serious adverse events that were thought to be related to the study drug.ConclusionThis is the first randomized controlled trial showing that inhibition of IL‐6 significantly improved the signs and symptoms of RA and normalized the acute‐phase reactants. Further research with multiple dosing is necessary to define the most appropriate therapeutic regimen of MRA in RA.
Induction of advanced glycation end products and alterations of the tensile properties of articular cartilage
Authors: Chen Albert C. , Temple Michele M. , Ng Darren M. , Verzijl Nicole , DeGroot Jeroen , TeKoppele Johan M. , Sah Robert L. 
Published: December 2002

AbstractObjectiveTo determine whether increasing advanced glycation end products (AGEs) in bovine articular cartilage to levels present in aged human cartilage modulates the tensile biomechanical properties of the tissue.MethodsAdult bovine articular cartilage samples were incubated in a buffer solution with ribose to induce the formation of AGEs or in a control solution. Portions of cartilage samples were assayed for biochemical indices of AGEs and tested to assess their tensile biomechanical properties, including stiffness, strength, and elongation at failure.ResultsRibose treatment of cartilage induced increases in tissue fluorescence, absorbance, and pentosidine content (P < 0.001 for each comparison) by amounts similar to those that occur during aging in humans. Ribose treatment of cartilage also induced an increase in dynamic modulus (60% increase) and strength (35% increase), and a decrease (25% decrease) in strain (P < 0.001 for each comparison).ConclusionThe concomitant increase in AGEs and alteration of tensile properties of cartilage after ribose treatment suggest that aging‐associated changes in AGEs have functional consequences for this tissue. The AGE‐associated increases in strength and stiffness of cartilage may be beneficial by counteracting the decreases in these properties that are associated with degeneration. Conversely, the AGE‐associated decrease in failure length, or increase in brittleness, together with increased stiffness may predispose cartilage to increased stress concentration, fracture, and aging‐associated biomechanical dysfunction.
Evidence for increased bone resorption in patients with progressive knee osteoarthritis: Longitudinal results from the Chingford study
Authors: Bettica Paolo , Cline Gary , Hart Deborah J. , Meyer Joan , Spector Tim D. 
Published: December 2002

AbstractObjectiveSeveral studies have suggested that increased subchondral bone turnover is a determinant of progression of osteoarthritis (OA). To test this hypothesis, the level of urinary N‐terminal type I collagen telopeptides (NTx) and C‐terminal type I collagen telopeptides (CTx), which are validated markers of bone resorption, was measured at 3 different time points in a subset of patients from the Chingford study.MethodsThe original Chingford study population comprised 1,003 women. From this group, postmenopausal women not receiving any bone‐modifying medication who had a baseline knee radiograph and a repeat radiograph 4 years later, and for whom a baseline lumbar spine bone mineral density (BMD) measurement was available, were identified and separated into 4 groups as follows: controls (n = 50), progressive OA (n = 71), nonprogressive OA (n = 36), and osteoporosis (n = 59). NTx and CTx were measured in urine samples collected at baseline, year 1, and year 2.ResultsPatient age and years since menopause were similar among groups at baseline. As expected, both body mass index (BMI) and BMD were lowest in patients with osteoporosis. Median resorption marker levels over the 3 time points were 31–87% higher in patients with either progressive OA or osteoporosis than in controls and patients with nonprogressive OA (P < 0.01, except for levels of CTx in patients with progressive OA versus nonprogressive OA). Levels of NTx and CTx did not differ significantly between women with progressive OA (defined either by the presence of osteophytes or by joint space narrowing) and those with osteoporosis or between controls and women with nonprogressive OA. Results were essentially unchanged after adjustment for age, BMI, BMD, and past use of hormone replacement therapy, or when NTx and CTx values at each time point were analyzed separately.ConclusionOur data demonstrate that bone resorption is increased in patients with progressive knee OA and is not increased in those with nonprogressive knee OA. The increase in bone resorption seen in patients with progressive knee OA is similar to that observed in patients with osteoporosis. Altered bone turnover may be a diagnostic or therapeutic target in patients with progressive OA.
Timing of total joint replacement affects clinical outcomes among patients with osteoarthritis of the hip or knee
Authors: Fortin Paul R. , Penrod John R. , Clarke Ann E. , St‐Pierre Yvan , Joseph Lawrence , Bélisle Patrick , Liang Matthew H. , Ferland Diane , Phillips Charlotte B. , Mahomed Nizar , Tanzer Michael , Sledge Clement , Fossel Anne H. , Katz Jeffrey N. 
Published: December 2002

AbstractObjectiveTo determine the predictors of outcome in patients with osteoarthritis 2 years after receiving total hip or knee replacement.MethodsA prospective cohort study of 222 osteoarthritis patients undergoing total hip or knee replacement in Boston and Montreal was done. Their postoperative outcomes at 6 months were previously reported. This followup reports on the outcomes after 2 years among the 165 patients (74%) who remained. The subjects were divided into 2 groups according to the median value of their preoperative Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function score. The Short Form 36‐item physical function subscale and the WOMAC pain and function subscale scores were collected at baseline and at 3, 6, and 24 months postoperatively. Clinical outcomes were analyzed at 2 years, using descriptive and multiple regression analyses.ResultsImprovements in pain and function at 2 years were similar to those observed at 6 months. Those subjects with the worst function and pain at the time of surgery (baseline) had comparatively worse function 2 years after surgery.ConclusionIn this comparison, the poor outcomes observed at 6 months following total joint replacement in patients with worse baseline functional status persisted after 2 years. Although there are no validated indications for when a patient should optimally have total joint replacement, these data suggest that timing of surgery may be more important than previously realized and, specifically, that performing surgery earlier in the course of functional decline may be associated with better outcome.
Up‐regulated expression of cartilage intermediate‐layer protein and ANK in articular hyaline cartilage from patients with calcium pyrophosphate dihydrate crystal deposition disease
Authors: Hirose Jun , Ryan Lawrence M. , Masuda Ikuko 
Published: December 2002

AbstractObjectiveExcess accumulation of extracellular inorganic pyrophosphate (ePPi) in aged human cartilage is crucial in calcium pyrophosphate dihydrate (CPPD) crystal formation in cartilage matrix. Two sources of ePPi are ePPi‐generating ectoenzymes (NTPPPH) and extracellular transport of intracellular PPi by ANK. This study was undertaken to evaluate the role of NTPPPH and ANK in ePPi elaboration, by investigating expression of NTPPPH enzymes (cartilage intermediate‐layer protein [CILP] and plasma cell membrane glycoprotein 1 [PC‐1]) and ANK in human chondrocytes from osteoarthritic (OA) articular cartilage containing CPPD crystals and without crystals.MethodsChondrocytes were harvested from knee cartilage at the time of arthroplasty (OA with CPPD crystals [CPPD], n = 8; OA without crystals [OA], n = 10). Normal adult human chondrocytes (n = 1) were used as a control. Chondrocytes were cultured with transforming growth factor β1 (TGFβ1), which stimulates ePPi elaboration, and/or insulin‐like growth factor 1 (IGF‐1), which inhibits ePPi elaboration. NTPPPH and ePPi were measured in the media at 48 hours. Media CILP, PC‐1, and ANK were determined by dot‐immunoblot analysis. Chondrocyte messenger RNA (mRNA) was extracted for reverse transcriptase–polymerase chain reaction to study expression of mRNA for CILP, PC‐1, and ANK. NTPPPH and ANK mRNA and protein were also studied in fresh frozen cartilage.ResultsBasal ePPi elaboration and NTPPPH activity in conditioned media from CPPD chondrocytes were elevated compared with normal chondrocytes, and tended to be higher compared with OA chondrocytes. Basal expression of mRNA for CILP (chondrocytes) and ANK (cartilage) was higher in both CPPD chondrocytes and CPPD cartilage extract than in OA or normal samples. PC‐1 mRNA was less abundant in CPPD chondrocytes and cartilage extract than in OA chondrocytes and extract, although the difference was not significant. CILP, PC‐1, and ANK protein levels were similar in CPPD, OA, and normal chondrocytes or cartilage extracts. Both CILP and ANK mRNA expression and ePPi elaboration were stimulated by TGFβ1 and inhibited by IGF‐1 in chondrocytes from all sources.ConclusionCILP and ANK mRNA expression correlates with chondrocyte ePPi accumulation around CPPD and OA chondrocytes, and all respond similarly to growth factor stimulation. These findings suggest that up‐regulated CILP and ANK expression contributes to higher ePPi accumulation from CPPD crystal–forming cartilage.
Effects of β2‐glycoprotein I and monoclonal anticardiolipin antibodies in platelet interaction with subendothelium under flow conditions
Authors: Font Josep , Espinosa Gerard , Tàssies Dolors , Pino Marc , Khamashta Munther A. , Gallart Teresa , Cervera Ricard , Escolar Ginés , Hughes Graham R. V. , Ingelmo Miguel , Ordinas Antoni , Reverter Joan‐Carles 
Published: December 2002

AbstractObjectiveTo evaluate whether the effect of human monoclonal anticardiolipin antibodies (aCL) on platelet interaction with the subendothelium under flow conditions is dependent on β2‐glycoprotein I (β2GPI).MethodsThree monoclonal IgM aCL with anti‐β2GPI activity (TM1B3, GR1D5, and EY2C9) obtained from patients with antiphospholipid syndrome, a monoclonal aCL with lupus anticoagulant activity but without anti‐β2GPI activity (FRO) obtained from a patient with a splenic lymphoma, and a control monoclonal IgM without aCL activity were used. TM1B3, GR1D5, EY2C9, FRO, and control IgM (30 μg/ml) were added to reconstituted blood containing gel‐filtered platelets (200 × 109/liter), factor VIII (100 units/dl), and fibrinogen (1.5 gm/liter). Samples were perfused (wall‐shear rate 800 seconds−1), with and without the addition of purified β2GPI (20 μg/ml), through annular chambers containing collagen‐rich denuded vascular segments, and the percentages of surface covered by platelets and by thrombi were evaluated.ResultsNo differences in the percentages of surface covered by platelets and by thrombi were observed among samples with TM1B3, GR1D5, EY2C9, FRO, and control IgM added when reconstituted blood samples without β2GPI were used. However, a significant increase in the percentage of surface covered by platelets was observed in the presence of TM1B3, GR1D5, and EY2C9 but not in the presence of FRO when samples containing β2GPI were used. Increased thrombi formation was induced by TM1B3 and GR1D5 but not by EY2C9 or FRO in samples with added β2GPI.ConclusionMonoclonal aCL require anti‐β2GPI activity to promote platelet interaction with the subendothelium under flow conditions.
Inhibition of adjuvant‐induced arthritis by systemic tissue inhibitor of metalloproteinases 4 gene delivery
Authors: Çeliker Mahmut Y. , Ramamurthy Nungavaram , Xu Jin‐Wen , Wang Mingsheng , Jiang Yangfu , Greenwald Robert , Shi Y. Eric 
Published: December 2002

AbstractObjectiveAn imbalance in the matrix metalloproteinase:tissue inhibitor of metalloproteinases (MMP:TIMP) ratio in favor of MMP appears to be an important determinant of tissue damage in arthritis. We undertook this study to explore whether reversal of this imbalance in favor of TIMP would alter this process and to examine the mechanism of this alteration.MethodsWe administered human TIMP‐4 by electroporation‐mediated intramuscular injection of naked DNA using the rat adjuvant‐induced arthritis (AIA) model.ResultsIntramuscular naked TIMP‐4 gene administration resulted in high circulating TIMP‐4 levels and completely abolished arthritis development in the rat AIA model. This inhibition was associated with significantly decreased MMP activity in the joint tissue as well as with significantly decreased serum and tissue tumor necrosis factor α levels and serum interleukin‐1α levels compared with animals with arthritis. The mutation of cysteine at position 1 of TIMP‐4 failed to block the development of AIA.ConclusionOur data indicate that TIMP‐4 is a potent antiinflammatory agent, and that its antiarthritis function may be mediated by MMPs. Arthritis‐inhibiting effects of TIMP‐4 may suggest a unique application of this gene therapy method for arthritis.
Nonrandom evolution of end‐stage osteoarthritis of the lower limbs
Authors: Shakoor Najia , Block Joel A. , Shott Susan , Case John P. 
Published: December 2002

AbstractObjectivePatients with unilateral hip or knee replacements for end‐stage osteoarthritis (OA) are at high risk for future progression of OA in other joints of the lower extremities, often requiring additional joint replacements. Although the risks of future surgery in the contralateral cognate joints (i.e., contralateral hip replacement after an initial hip replacement) have been evaluated, the evolution of end‐stage hip OA to OA involving the knee joints, and vice versa (i.e., noncognate progression) has not been investigated. Because characterization of OA progression in noncognate joints may shed light on the pathogenesis of multijoint OA, we investigated the pattern of evolution of end‐stage lower extremity OA in a large, clinical cohort.MethodsTotal joint replacement (TJR) was selected as a marker of end‐stage OA, and a database comprising all lower extremity TJRs performed at a large referral center between 1981 and 2001 was accessed. Of the 5,894 patients identified, 486 patients with idiopathic OA who underwent hip replacement and 414 who underwent initial knee replacement were analyzed to determine the relative likelihood of subsequent TJRs. Patients with the systemic inflammatory arthropathy, rheumatoid arthritis (RA), were evaluated as a control population because RA progression is not considered to be a primarily mechanically mediated process.ResultsThe contralateral cognate joint was the most common second joint to undergo replacement in both the OA and the RA groups. However, in OA patients for whom the second TJR was in a noncognate joint, that joint was >2‐fold more likely to be on the contralateral limb than on the ipsilateral limb (hip to knee P < 0.001; knee to hip P = 0.013). In contrast, among the RA cohort, the evolution was random and no laterality for noncognate TJR was observed at either the hip or the knee (P = 0.782).ConclusionThis characterization of end‐stage lower extremity OA demonstrates that the disease evolves nonrandomly; after 1 joint is replaced, the contralateral limb is significantly more likely to show progression of OA than is the ipsilateral limb. Thus, OA in 1 weight‐bearing joint appears to influence the evolution of OA in other joints. The absence of such laterality in RA suggests that OA progression may be mediated by extrinsic factors such as altered joint loading.
Growth‐related oncogene α induction of apoptosis in osteoarthritis chondrocytes
Authors: Borzi Rosa Maria , Mazzetti Ilaria , Magagnoli Giorgia , Paoletti Samantha , Uguccioni Mariagrazia , Gatti Rita , Orlandini Guido , Cattini Luca , Facchini Andrea 
Published: December 2002

AbstractObjectiveTo evaluate the apoptotic effect of the chemokine growth‐related oncogene α (GROα), which we recently reported to be up‐regulated in osteoarthritis (OA) chondrocytes. Chondrocyte apoptosis is considered to be a major determinant of cartilage damage in OA, a disease resulting from the aberrant production of inflammatory mediators (cytokines and chemokines) and effectors (matrix metalloproteinases and reactive oxygen and nitrogen species) by chondrocytes.MethodsWe investigated the apoptotic effect of GROα on isolated human cells and on in vitro–cultured cartilage explants by conventional methods (morphology, detection of DNA fragmentation in situ and in solution, exposure of phosphatidylserine) and by analysis of “early” biochemical events (plasma membrane depolarization, activation of caspase 3, and phosphorylation of c‐Jun N‐terminal kinase/stress‐activated protein kinase).ResultsWe clearly demonstrated that GROα was able to initiate a series of morphologic, biochemical, and molecular changes that led to chondrocyte apoptosis. Moreover, we found that additional signals delivered from the extracellular matrix (ECM) were essential in the control of chondrocyte susceptibility to GROα‐induced apoptosis, since cell death was detected only when cells were stimulated after reestablishment of their proper interactions with the ECM, or in cartilage explant samples with reduced ECM, as indicated by decreased Safranin O staining.ConclusionGROα can induce apoptosis in articular chondrocytes, and the induction is dependent upon additional signals from the ECM. These findings are relevant to understanding the pathogenesis of OA, in view of the availability of the GROα chemokine in the joint space in the course of this rheumatic disease.