bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tendon degeneration is not mediated by regulation of Toll‐like receptors 2 and 4 in human tenocytes
Authors: de Mos Marieke , Joosten Leo A.B. , Oppers‐Walgreen Birgitte , van Schie Johannes T.M. , Jahr Holger , van Osch Gerjo J.V.M. , Verhaar Jan A.N. 
Published: January 2009

AbstractWe hypothesized that expression of Toll‐like receptors (TLRs) 2 and 4 by tenocytes is involved in the catabolic processes of tendon degeneration. We investigated TLR2 and TLR4 expression by tenocytes in healthy and tendinotic Achilles tendons. We also investigated whether TLR2 and TLR4 could be upregulated in tendon explants using proinflammatory cytokines interleukin (IL)‐1β and tumor necrosis factor alphpa (TNFα). Peroperatively harvested healthy (n = 5) and tendinotic (n = 13) Achilles tendon samples were examined by real‐time RT‐PCR and immunohistochemical staining for TLR2 and TLR4. In addition, the catabolic process in tendinopathy was analyzed by real‐time RT‐PCR for matrix metalloproteinases MMP1, MMP3, MMP9, and MMP13. Furthermore, healthy tendon explants were cultured in the presence of 20 ng/ml IL‐1β (n = 10) or 10 ng/mL TNFα (n = 8) for 4, 24, 48, and 72 h before analysis of TLR and MMP expression levels. Although mRNA levels for both TLR2 and TLR4 were detected in healthy and tendinotic Achilles tendons, we could not confirm expression of these receptors by immunohistochemical staining in either healthy or tendinotic tendon samples. Both receptors did not show significant transcriptional regulation in tendinopathy, although MMP3 was downregulated and MMP9 was upregulated in tendinopathy. In tendon explant cultures TLR2 mRNA was upregulated by TNFα (p < 0.05) and IL‐1β (not significant). TLR4 gene expression was not altered by addition of IL‐1β or TNFα. Tendon tissue can be stimulated to increase TLR2 gene expression by addition of catabolic factors TNFα or IL‐1β. However, the catabolic processes in Achilles tendinopathy cannot be attributed to regulation of TLR2 and TLR4 by tenocytes. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1043–1047, 2009
Total knees designed for normal kinematics evaluated in an up‐and‐down crouching machine
Authors: Yildirim Gokce , Walker Peter S. , Boyer Jason 
Published: January 2009

AbstractWe constructed a crouching machine to study the motion of the knee joint, in which a motor was used to wind the quadriceps tendon so as to move the knee from high flexion to extension and back into flexion, while springs simulated hamstrings forces. Seven human cadaveric knees were tested intact and then after anterior cruciate ligament (ACL) resection. Motions of the femur, tibia, and patella were recorded by an optical tracking system. We then inserted plastic models representing commonly used total condylar and posterior stabilized knee replacement designs. Femoral motion was described by successive positions of the transverse axis of the femur projected onto the tibial surface. In the knee replacements, motions were similar to that of an ACL‐deficient knee. We then tested two new designs with features intended to prevent anterior paradoxical sliding and to promote a medial pivot motion with femoral rollback primarily on the lateral side. The motion path more closely followed that of the normal intact knee. We concluded that motion guiding features in a total knee replacement could reproduce a normal neutral path that might result in functional improvements for the patient. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1022–1027, 2009
Fixation of hydroxyapatite‐coated revision implants is improved by the surgical technique of cracking the sclerotic bone rim
Authors: Elmengaard Brian , Bechtold Joan E. , Chen Xinqian , Søballe Kjeld 
Published: January 2009

AbstractRevision joint replacement has poorer outcomes that have been associated with poorer mechanical fixation. We investigate a new bone‐sparing surgical technique that locally cracks the sclerotic bone rim formed during aseptic loosening. We inserted 16 hydroxyapatite‐coated implants bilaterally in the distal femur of eight dogs, using a controlled weight‐bearing experimental model that replicates important features of a typical revision setting. At 8 weeks, a control revision procedure and a crack revision procedure were performed on contralateral implants. The crack procedure used a splined tool to perform a systematic local perforation of the sclerotic bone rim of the revision cavity. After 4 weeks, the hydroxyapatite‐coated implants were evaluated for mechanical fixation by a push‐out test and for tissue distribution by histomorphometry. The cracking revision procedure resulted in significantly improved mechanical fixation, significantly more bone ongrowth and bone volume in the gap, and reduced fibrous tissue compared to the control revision procedure. The study demonstrates that the sclerotic bone rim prevents bone ingrowth and promotes fixation by fibrous tissue. The effect of the cracking technique may be due to improved access to the vascular compartment of the bone. The cracking technique is a simple surgical method that potentially can improve the fixation of revision implants in sclerotic regions important for obtaining the fixation critical for overall implant stability. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 996–1001, 2009
The proximal hip joint capsule and the zona orbicularis contribute to hip joint stability in distraction
Authors: Ito Hiroshi , Song Yongnam , Lindsey Derek P. , Safran Marc R. , Giori Nicholas J. 
Published: January 2009

AbstractThe structure and function of the proximal hip joint capsule and the zona orbicularis are poorly understood. We hypothesized that the zona orbicularis is an important contributor to hip stability in distraction. In seven cadaveric hip specimens from seven male donors we distracted the femur from the acetabulum in a direction parallel to the femoral shaft with the hip in the neutral position. Eight sequential conditions were assessed: (1) intact specimen (muscle and skin removed), (2) capsule vented, (3) incised iliofemoral ligament, (4) circumferentially incised capsule, (5) partially resected capsule (distal to the zona orbicularis), (6) completely resected capsule, (7) radially incised labrum, and (8) completely resected labrum. The reduction of the distraction load was greatest between the partially resected capsule phase and completely resected capsule phase at 1, 3, and 5 mm joint distraction (p = 0.018). The proximal to middle part of the capsule, which includes the zona orbicularis, appears grossly and biomechanically to act as a locking ring wrapping around the neck of the femur and is a key structure for hip stability in distraction. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 989–995, 2009
Binding Energetics of Lysozyme to Copolymers of N‐Isopropylacrylamide with Sodium Sulfonated Styrene
Authors: Burova Tatiana V. , Grinberg Natalia V. , Grinberg Valerij Ya. , Tang Yecang , Zhang Guangzhao , Khokhlov Alexei R. 
Published: January 2009

AbstractInterpolyelectrolyte complexes of lysozyme with thermosensitive N‐isopropylacrylamide–sodium sulfonated styrene copolymers of different charge density were investigated by high‐sensitivity differential scanning calorimetry (HS‐DSC) at pH 4.6–7.2 and low ionic strength. A general property of the complexes for all copolymers investigated was a decrease in the conformational stability of the bound protein. This suggested the preferential binding of the unfolded protein to the polymer matrix. The isotherms of lysozyme binding to the copolymers were derived from the HS‐DSC data. They indicate that the binding is irreversible and charge stoichiometric.magnified image
Liquid‐Glassy Polymer Interphases: Diffusion Kinetics in Conditions of Unlimited Liquid Supply
Authors: Tomba J. Pablo , Carella José M. , Pérez Claudio J. , Pastor José M. 
Published: January 2009

AbstractWe investigate evidences of diffusion controlled by mechanical relaxation of the glassy matrix, i.e. Case‐II mechanism, in a series of liquid/glassy interphases formed by PS and PPO as liquid and glassy components, respectively. Diffusion experiments were performed in conditions of unlimited supply of the liquid polymer, parallel to those in which Case‐II has been effectively verified. Interphase profiles were obtained via optical sectioning with confocal Raman microspectroscopy (CRM). We observed that interphase diffusion kinetics were markedly Fickean, in contrast with interpretations from other authors that invoke Case‐II to explain the mechanisms that rule interphase evolution in these systems.magnified image
Metabolism of anandamide by COX‐2 is necessary for endocannabinoid‐induced cell death in tumorigenic keratinocytes
Authors: Van Dross Rukiyah T. 
Published: January 2009

AbstractNonmelanoma skin cancer is the most prevalent cancer in the United States with ∼1.25 million new cases diagnosed each year. Cyclooxygenase‐2 (COX‐2) expression is commonly elevated in these and other epithelial tumors. Cyclooxygenases metabolize arachidonic acid to prostaglandins, which promote growth and survival of tumor cells. COX‐2 also metabolizes endocannabinoids forming prostaglandin‐ethanolamides (PG‐EA); however, the role of these lipid molecules in tumor cell survival is unclear. The goal of this research is to determine if the metabolic products of COX‐2 contribute to endocannabinoid‐induced cell death. Anandamide [also known as arachidonyl ethanolamide (AEA)] induced cell death in the COX‐2 overexpressing squamous carcinoma cell line JWF2. In contrast, AEA did not initiate cell death in HaCaT keratinocytes, which express low basal levels of COX‐2. Resistance to AEA‐mediated cell death in HaCaT cells was reversed by overexpressing COX‐2 in these cells. Next, ELISA assays were carried out to identify prostaglandins involved in AEA‐mediated cell death. D‐type prostaglandins were predominantly formed in AEA‐exposed JWF2 cells although significant increases in E‐ and F‐type prostaglandins were also seen. Cells were then treated with various prostaglandins or PG‐EA to determine the contribution of each to AEA‐induced cell death. PGD2 and PGD2‐EA were found to be cytotoxic to JWF2 keratinocytes and the PGD2 dehydration products, PGJ2 and 15‐deoxy Δ12,14 PGJ2, were also potent inducers of cell death. These results suggest that AEA selectively induces cell death in tumorigenic keratinocytes due to COX‐2 overexpression and the resulting metabolism of AEA to cytotoxic prostaglandins. © 2009 Wiley‐Liss, Inc.
Association of variants in the interleukin‐27 and interleukin‐12 gene with nasopharyngeal carcinoma
Authors: Wei Ye‐Sheng , Lan Yan , Luo Bin , Lu Dong , Nong Hong‐Bing 
Published: January 2009

AbstractNasopharyngeal carcinoma (NPC) is multifactorial, and the genetic background may be a crucial etiologic factor. Interleukin‐12 (IL‐12) is a multifunctional cytokine that induces interferon (IFN)‐gamma secretion and plays an important role in antitumor immunity. Interleukin‐27 (IL‐27) is a novel IL‐12 family member, the present studies demonstrate that IL‐27 mediates potent antitumor activity. Variations in the DNA sequence in the IL‐12 and IL‐27 gene may lead to altered cytokines production and/or activity, and so this can modulate an individual's susceptibility to NPC. To test this hypothesis, we investigated the relationship of IL‐12 and IL‐27 gene polymorphisms and NPC in a Chinese population. We analyzed single nucleotide polymorphisms (SNPs) of IL‐12 gene 16974 A/C and IL‐27 gene −964 A/G, 2905 T/G, 4730 T/C in 302 patients with NPC and 310 age‐ and sex‐matched controls, using polymerase chain reaction–restriction fragment length polymorphism (PCR–RFLP) and DNA sequencing methods. There were significant differences in the genotype and allele distribution of 16974 A/C polymorphism of the IL‐12 gene among cases and controls. The 16974 CC and AC genotypes were associated with a significantly increased risk of NPC as compared with the 16974 AA genotypes (OR = 2.225, 95% CI 1.395–3.549, P = 0.001 and OR = 1.834, 95% CI 1.239–2.716, P = 0.002, respectively). The 16974 C allele was associated with a significantly increased risk of NPC as compared with the 16974 A allele (OR = 1.334, 95% CI 1.065–1.670, P = 0.012). However, genotype and allele frequencies of the IL‐27 gene −964 A/G, 2905 T/G, 4730 T/C polymorphisms in NPC patients were not significantly different than that in healthy controls (P > 0.05). Our data suggest that IL‐12 gene may play a role in the development of NPC. © 2009 Wiley‐Liss, Inc.
Legendre multiscaling functions for solving the one‐dimensional parabolic inverse problem
Authors: Yousefi S.A. , Dehghan Mehdi 
Published: January 2009

AbstractAn inverse problem concerning diffusion equation with a source control parameter is investigated. The approximation of the problem is based on the Legendre multiscaling basis. The properties of Legendre multiscaling functions are first presented. These properties together with Galerkin method are then utilized to reduce the inverse problem to the solution of algebraic equations. Illustrative examples are included to demonstrate the validity and applicability of the new technique. © 2009 Wiley Periodicals, Inc. Numer Methods Partial Differential Eq, 2009
Relapses of optic pathway tumors after first‐line chemotherapy
Authors: de Haas Valérie , Grill Jacques , Raquin Marie‐Anne , Couanet Dominique , Habrand Jean‐Louis , Sainte‐Rose Christian , Laithier Véronique , Kieffer Virginie , Kalifa Chantal 
Published: January 2009

AbstractBackgroundChemotherapy is accepted as first‐line conservative treatment of optic pathway tumors in patients younger than 5. Limited data are available on the outcome of patients with recurrence/progression after initial chemotherapy.ProcedureData on 68 children with Optic Pathway Tumors (OPT) treated with first‐line Baby Brain (BBSFOP) chemotherapy at the Gustave Roussy Institute in Villejuif between 1990 and 2005 were reviewed.ResultsDuring a median follow‐up of 6 years, 44 (65%) patients were diagnosed with one or more relapses. Most of the relapses occurred during the first 6 years of life. Overall and progression‐free survival rates at 5 years after first relapse were 64% and 14%, respectively. First relapse was treated with chemotherapy, radiotherapy or surgery in 28, 9, and 6 patients, respectively. Best response to second‐line chemotherapy was partial response in 10, stable disease in 10, and progressive disease in 8 patients. Patients with objective radiologic response to first‐line chemotherapy, had a greater chance to respond again to second‐line chemotherapy (RR = 90% vs. 15%, P = 0.003). Median time to progression after first relapse was 1.7, 2.5, and 3.1 years after surgery, chemotherapy and radiotherapy, respectively. Finally, 25 (37%) patients received radiotherapy at a median age of 6.7 years.ConclusionsSecond‐line chemotherapy can be effective in the treatment of relapses after first‐line chemotherapy and delay further the need for RT, especially in patients whose tumor initially responded to chemotherapy. Despite the desire to avoid irradiation in treatment of young patients with OPT, radiotherapy was used for 37% of patients, usually before the age of 10. Pediatr Blood Cancer 2009;52:575–580. © 2009 Wiley‐Liss, Inc.
Tacrolimus as an alternative to cyclosporine in the maintenance phase of immunosuppressive therapy for severe aplastic anemia in children
Authors: Alsultan Abdulrahman , Goldenberg Neil A. , Kaiser Nicole , Graham Douglas K. , Hays Taru 
Published: January 2009

AbstractObjectiveGiven the paucity of data on the use of agents other than cyclosporine (CsA) in the maintenance phase of immunosuppressive therapy (IST) for severe aplastic anemia (SAA) in children, we sought to describe our experience with tacrolimus in pediatric SAA, and to compare outcomes with a preceding series of patients who received CsA.MethodsEight patients with SAA diagnosed between 2003 and 2008 for whom no human leukocyte antigen (HLA)‐matched sibling donor was identified underwent tacrolimus‐based IST. These children were compared with a previously described series of 13 patients who had undergone CsA‐based IST at our institution between 1990 and 2003. All patients initially received equine antithymocyte globulin (ATG) and corticosteroids.ResultsComplete response (CR) rate was 88% for tacrolimus and 85% for CsA. Median time to CR was approximately 7 months in both groups. Median follow‐up duration was 2.4 years for tacrolimus and 8.4 years for CsA. Among responders with de novo SAA, relapse rate was 25% (n = 1) at 2 years for tacrolimus and 0% at 2 years and 23% (n = 3) at 5 years for CsA; no significant difference in relapse‐free survival was detected between the two groups (P = 0.07). Paroxysmal nocturnal hemoglobinuria was seen in one patient on tacrolimus who had relapsed after CsA‐based IST. Tacrolimus‐based IST was well‐tolerated.ConclusionThese data provide evidence that tacrolimus may be a suitable alternative to CsA as part of an IST regimen for SAA in children who lack an HLA‐matched sibling and may have a more favorable profile of side effects than CsA. Pediatr Blood Cancer 2009;52:626–630. © 2009 Wiley‐Liss, Inc.
Reduced risk of secondary leukemia with fewer cycles of dose‐intensive induction chemotherapy in patients with neuroblastoma
Authors: Kushner Brian H. , Kramer Kim , Modak Shakeel , Qin Li‐Xuan , Yataghena Karima , Jhanwar Suresh C. , Cheung Nai‐Kong V. 
Published: January 2009

AbstractBackgroundWe report a prospective study of secondary leukemia (SL)/myelodysplastic syndrome (MDS) in neuroblastoma (NB) patients treated with ≥5 cycles of dose‐intensive chemotherapy.ProcedureNB patients received induction with high‐dose cyclophosphamide (4,200 mg/m2)‐doxorubicin (75 mg/m2)‐vincristine (cycles 1, 2, 4, 6, 8), and high‐dose cisplatin (200 mg/m2)‐etoposide (600 mg/m2) (cycles 3, 5, 7). Bone marrow was examined every 1–3 months for ≥36 months, with inclusion of extensive chromosomal studies 1‐3 months post‐induction and 1–2×/year thereafter.ResultsOne hundred eight four patients received 5 (n = 76), 6 (n = 45), 7 (n = 59), or 8 (n = 4) cycles. Eight patients developed SL/MDS (only one each in the 5‐ and 6‐cycle groups), at 12–50 months, including two cases detected in surveillance studies. Among 108 patients who received ≥6 cycles, the 5‐year cumulative incidence was 7.1% (95% CI: 2%, 12.2%), versus 0% among 54 patients who received 5 cycles without maintenance oral etoposide. Five‐year cumulative incidences were 1.46%, 2.28%, and 8.47% among patients in the 5‐, 6‐, and 7‐cycle groups, with fewer cycles having a significantly lower risk (P = 0.048). There was no significant association of risk with potentially leukemogenic consolidative treatments (targeted radiotherapy, myeloablative therapy, and oral etoposide).ConclusionsReducing the number of dose‐intensive cycles significantly decreases the risk of SL/MDS, yielding 5‐year rates matching the low range (0.4–2.2%) reported for moderate‐dose combination chemotherapy regimens used against other pediatric solid tumors. Pediatr Blood Cancer 2009;53:17–22. © 2009 Wiley‐Liss, Inc.
Evaluation of risk factors for elevated tricyclic antidepressant plasma concentrations
Authors: Billups Sarah J. , Delate Thomas , Dugan Daniel 
Published: January 2009

AbstractPurposeTo quantify the effect of clinical and demographic factors on the risk of elevated and toxic tricyclic antidepressant (TCA) plasma concentrations (Cp) and to describe the rates of elevated and toxic TCA Cp.MethodsThis matched, case‐control study was conducted among adult patients enrolled in a group model HMO who had a TCA Cp laboratory measurement and purchased at least one TCA prescription for either amitriptyline or nortriptyline during the 70 days preceding the TCA Cp measurement. Predictive models of experiencing an elevated or toxic Cp were created using multivariate conditional logistic regression.ResultsAt least one Cp was drawn in 1057 unique patients with a TCA purchase. Of these, 18.4% (194/1057) patients (cases) had an elevated TCA Cp and were matched to 716 non‐elevated Cp patients. Additionally, 27.3% (53/194) of the cases (matched to 196 controls) experienced a toxic TCA Cp. The best fitting model of an elevated TCA Cp included TCA dose category (daily doses ≥150 mg, OR = 4.08; doses of 50 to <100 mg, OR = 0.36; and doses <50 mg, OR = 0.18, p < 0.05 for all comparisons), female gender (OR = 1.78, p < 0.05) and concurrent use of fluoxetine or paroxetine (OR = 1.75, p < 0.05). The best fitting predictive model of a toxic TCA Cp included the same factors as for the predictive model of an elevated TCA Cp.ConclusionsRecognizing and monitoring predictors of elevated or toxic TCA Cps, including increasing TCA dose, female gender, and concurrent use of fluoxetine or paroxetine, may reduce serious adverse drug reactions and deaths in the TCA‐receiving patient population. Copyright © 2009 John Wiley & Sons, Ltd.
Early adverse drug event signal detection within population‐based health networks using sequential methods: key methodologic considerations
Authors: Brown Jeffrey S. , Kulldorff Martin , Petronis Kenneth R. , Reynolds Robert , Chan K. Arnold , Davis Robert L. , Graham David , Andrade Susan E , Raebel Marsha A. , Herrinton Lisa , Roblin Douglas , Boudreau Denise , Smith David , Gurwitz Jerry H. , Gunter Margaret J. , Platt Richard 
Published: January 2009

AbstractPurposeActive surveillance of population‐based health networks may improve the timeliness of detection of adverse events (AEs). Our objective was to expand our previous signal detection work by investigating the effect on signal detection of alternative study specifications.MethodsWe compared the signal detection performance under various study specifications using historical data from nine health plans involved in the HMO Research Network's Center for Education and Research on Therapeutics (CERT). Five drug‐event pairs representing generally accepted associations with an AE and two pairs representing “negative controls” were analyzed. Alternative study specifications related to the definition of incident users and incident AEs were assessed and compared to our previous findings.ResultsRelaxing the incident AE exclusion criteria by (1) including members with prior outpatient diagnoses of interest and (2) halving (to 90 days) the time window specified to define incident exposure and diagnoses increased the number of members under surveillance and as a consequence increased the number of exposed days and diagnoses by about 10–20%. The alternative specifications tend to result in earlier signal detection by 10–16 months, a likely consequence of more exposures and events entering the analysis.ConclusionsThis paper provides additional preliminary information related to conducting prospective safety monitoring using health plan data and sequential analytic methods. Our findings support continued investigation of using health plan data and sequential analytic methods as a potentially important contribution to active drug safety surveillance. Copyright © 2009 John Wiley & Sons, Ltd.