bluuebunny/crossref_metadata_2025_split huggingface dataset:
Lysophosphatidic Acid Receptors LPA1and LPA3Promote CXCL12-Mediated Smooth Muscle Progenitor Cell Recruitment in Neointima Formation
Authors: Subramanian Pallavi , Karshovska Ela , Reinhard Patricia , Megens Remco T.A. , Zhou Zhe , Akhtar Shamima , Schumann Uwe , Li Xiaofeng , van Zandvoort Marc , Ludin Christian , Weber Christian , Schober Andreas 
Published: April 2010

Rationale:The chemokine CXCL12 (CXC motif ligand 12) and its receptor CXCR 4 (CXC motif receptor 4) direct the recruitment of smooth muscle progenitor cells (SPCs) in neointima formation after vascular injury. Lysophosphatidic acid (LPA) induces CXCL12 and neointimal accumulation of smooth muscle cells (SMCs) in uninjured arteries. Thus, we hypothesize that LPA may regulate CXCL12-mediated vascular remodelling.Objectives:We evaluated the role of LPA receptors in initiating CXCL12-dependent vascular repair by SPCs.Methods and Results:Wire-induced carotid injury was performed in apolipoprotein E−/−mice on western-type diet. LPA receptor expression was studied by immunostaining and quantitative RT-PCR. LPA receptors LPA1and LPA3were detected in the media of uninjured arteries and in the injury-induced neointima. LPA3mRNA was upregulated and LPA1mRNA downregulated at one week after injury. The LPA1/3antagonist Ki16425 inhibited neointima formation by 71% and reduced both relative neointimal SMCs and the macrophage content. Additionally, neointimal hypoxia-inducible factor-1α and CXCL12 expression, the injury-induced peripheral stem cell antigen-1 (Sca-1)+/Lin−SPC mobilization, and the neointimal recruitment of Sca-1+SMCs were inhibited by Ki16425. In wild type mice, LPA20:4 increased CXCL12 and hypoxia-inducible factor-1α expression in carotid arteries as early as 1 day following short-term endoluminal incubation. LPA20:4-induced SPC mobilization and neointima formation were blocked by Ki16425, LPA1- and LPA3-specific small interfering (si)RNA, and the CXCR4 antagonist POL5551. Ki16425 reduced LPA20:4-mediated neointimal recruitment of SPC as demonstrated by 2-photon microscopy in bone marrow chimeric mice after repopulation with SM22-LacZ transgenic, hematopoietic cells. Moreover, POL5551 decreased the neointimal accumulation of CXCR4+SMCs.Conclusions:LPA1and LPA3promote neointima formation through activation of CXCL12-mediated mobilization and recruitment of SPCs.
Preservation of GABAAReceptor Function by PTEN Inhibition Protects Against Neuronal Death in Ischemic Stroke
Authors: Liu Baosong , Li Lijun , Zhang Quanguang , Chang Ning , Wang Dianshi , Shan Yuexin , Li Lei , Wang Hanbin , Feng Hua , Zhang Liang , Brann Darrell W. , Wan Qi 
Published: April 2010

Background and Purpose—Downregulation of the tumor suppressor, phosphatase and tensin homolog deleted on chromosome 10 (PTEN), is thought to be a novel neuroprotective strategy in ischemic stroke, but the underlying mechanisms remain unclear. In this study, we aimed to validate the use of PTEN regulation of γ-aminobutyric acid subtype A receptors (GABAARs) as a molecular target for the treatment of ischemic stroke. Because suppression of GABAARs contributes to ischemic neuron death, describing the intracellular signaling that interacts with GABAARs in ischemic neurons would provide a molecular basis for novel stroke therapies.Methods—We measured surface GABAAR expression by immunocytochemical labeling and surface protein biotinylation assay. Knockdown and overexpression approaches were used to test the effects of PTEN on the expression and function of GABAARs. Neuronal death was detected in both in vitro and in vivo stroke models.Results—The knockdown and overexpression approaches provided the first evidence that PTEN negatively regulated membrane expression and function of GABAARs in rat hippocampal neurons. Importantly, we demonstrated that a PTEN inhibitor prevented the reduction of surface GABAARs in injured hippocampal neurons subjected to oxygen-glucose deprivation, an in vitro insult that mimics ischemic injury, whereas a GABAAR antagonist significantly reduced this PTEN inhibitor–induced neuroprotection in both the in vitro and in vivo ischemic stroke models.Conclusions—Our study provides direct evidence that downregulation of PTEN protects against ischemic neuron death by preserving GABAAR function. Targeting this pathway may be an effective strategy for development of selective, potent stroke treatments.
Hospital psychiatric comorbidity and its role in heroin dependence treatment outcomes using naltrexone implant or methadone maintenance
Authors: Ngo Hanh TT , Tait Robert J , Hulse Gary K 
Published: April 2010

Our objectives were to (i) estimate lifetime prevalence of psychiatric comorbidity in heroin users and (ii) evaluate psychiatric comorbidity as a predictor of drug-related hospitalization following either (a) methadone maintenance or (b) naltrexone implant treatment. Our method consisted of retrospective, longitudinal follow-up using prospectively collected, state-wide hospital data on two cohorts of heroin-dependent persons (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition), first time treated with naltrexone implant ( n = 317) or methadone ( n = 521) between January 2001 and December 2002. Outcome measures were: (i) prevalence of comorbidity and (ii) changes in risk for drug-related hospitalization – categorized as ‘opioid drugs’, ‘non-opioid drugs’, and ‘any drug’ – to 3.5 years post-treatment. Nearly 32% had psychiatric comorbidity. In both cohorts, comorbid patients generally had significantly greater odds of drug-related hospitalization pre-treatment compared with non-comorbid counterparts. These differences generally reduced in magnitude post-treatment. Comorbid naltrexone-treated patients had less ‘opioid’ and ‘any drug’ related hospitalizations post-treatment. Similarly, comorbid methadone-treated patients had reduced hospitalization risk for ‘non-opioid’ and ‘any drug’ related hospitalization post-treatment. Treatment of persons without depression, anxiety, or personality disorder with naltrexone implant was associated with increased risk of ‘non-opioid’ drug-related hospitalization, while methadone treatment was associated with increased risk of ‘opioid’ drug-related hospitalization. Although comorbid heroin users entered treatment with significantly higher risk of drug-related hospitalization than non-comorbid users, substantial reductions in drug-related hospitalization were generally observed post-treatment. This challenges the view that comorbidity predicts poor drug treatment outcomes. Differences in research methodology were noted; recommendation for rigorous analytical methodology in future research on assessing treatment outcomes was accordingly offered.
Menstrual and nonmenstrual migraines differ in women with menstrually-related migraine
Authors: Pinkerman Brenda , Holroyd Kenneth 
Published: April 2010

Introduction: We compared migraine features and acute therapy response in menstrually-related migraines (MRMs) and non-menstrually-related migraines (NMRMs).Methods: Women with frequent, disabling migraines were prospectively diagnosed with MRM according to the International Classification of Headache Disorders (ICHD-II; N = 107) criteria using a daily electronic headache dairy. Participants received individualized acute therapy while free of prophylactic migraine medications.Results: Repeated measures logistic regression revealed MRMs were longer (23.4 vs. 16.1 hours, odds ratio [OR] = 1.01, confidence interval [CI] 1.01, 1.02) and more likely associated with disability (85.6% vs. 75.6%, OR = 1.82, CI 1.27, 2.58) than NMRMs. MRMs were also less responsive to acute therapy (two-hour pain-free response = 6.7% vs. 13.4%, OR = .45, CI .26, .80) and reoccurred more frequently within 24 hours after a four-hour pain-free response (36.0% vs. 19.6%, OR = 2.12, CI 1.27, 3.53) than NMRMs.Discussion: These results support the proposed ICHD-II classification of MRMs and suggest that MRMs may require a treatment approach different from that for NMRMs.
A Biomechanical Analysis of Anterior Bankart Repair Using Suture Anchors
Authors: Nho Shane J. , Frank Rachel M. , Van Thiel Geoffrey S. , Wang Fan Chia , Wang Vincent M. , Provencher Matthew T. , Verma Nikhil N. 
Published: April 2010

Background: Arthroscopic repair of anterior Bankart lesions is typically done with single-loaded suture anchors tied with simple stitch configuration. Hypothesis: The knotless suture anchor will have similar biomechanical properties compared with two types of conventional suture anchors. Study Design: Controlled laboratory study. Methods: Fresh-frozen shoulders were dissected and an anteroinferior Bankart lesion was created. For phase 1, specimens were randomized into either simple stitch (SSA) or knotless suture anchors (KSA) and loaded to failure. For phase 2, specimens were randomized into 1 of 4 repair techniques and cyclically loaded then loaded to failure: (1) SSA, (2) suture anchor with horizontal mattress configuration, (3) double-loaded suture anchor with simple stitch configuration, or (4) KSA. Data recorded included mode of failure, ultimate load to failure, load at 2 mm of displacement, as well as displacement during cyclical loading. Results: For phase 1, the load required to 2 mm displacement of the repair construct was significantly greater in SSA (66.5 ± 21.7 N) than KSA (35.0 ± 12.5 N, P = .02). For phase 2, there was a statistically significant difference in ultimate load to failure among the 4groups, with both the single-loaded suture anchor with simple stitch (184.0 ± 64.5 N), horizontal mattress stitch (189.0 ± 65.3N), and double-loaded suture anchor with simple stitch (216.7 ± 61.7 N) groups having significantly ( P < .05) higher loads than the knotless group (103.9 ± 52.8 N). There was no statistically significant difference ( P > .05) among the 4 groups in displacement after cyclical loading or load at 2 mm of displacement. Conclusion: Both knotless and simple anchor configurations demonstrated similar single loads to failure (without cycling); however, the knotless device required less single load to displace 2 mm. All repair stitches, including simple, horizontal, and double-loaded performed similarly. Clinical Relevance: The findings may suggest that with cyclical loading up to 25 N there is no difference in gapping greater than 2mm, but a macrotraumatic event may demonstrate a difference in fixation during the initial postoperative period. Additional in vivo studies are needed to determine whether these differences affect the integrity of the repair construct and, ultimately, the clinical outcome.
Clinical Experiences With Autologous Osteochondral Mosaicplasty in an Athletic Population
Authors: Hangody László , Dobos Jozsef , Baló Eszter , Pánics Gergely , Hangody Laszlo Rudolf , Berkes Istvan 
Published: April 2010

Background: Several methods are used to treat focal chondral and osteochondral defects on the weightbearing surfaces of synovial joints. Autologous osteochondral grafting is 1 option used to replace hyaline cartilage in the defect. Hypothesis: Mosaicplasty is effective in returning elite athletes to participation in sports. Study Design: Case series; Level of evidence, 4. Methods: In 3 institutes, 354 of 383 patients were followed from 2 to 17 years (average, 9.6 years). The results of mosaicplasty were prospectively evaluated at 6 weeks, 3 months, 6 months, and yearly with patient-reported outcomes measures and radiographs. Results: Slight or moderate degenerative changes (Fairbank grade I or II) were detected preoperatively in 27% of the cases and in 36% of the cases at follow-up. Fairbank grade III changes were observed in 5 cases. An average radiographic deterioration of 0.32 on the Fairbank scale was detected (preoperative, 0.34; postoperative, 0.66). Good to excellent results were found in 91% of femoral mosaicplasties, 86% of tibial, and 74% of patellofemoral; 92% of talar mosaicplasties had similar results (Hannover ankle scoring system). Patellofemoral pain related to graft harvest was observed in 5% of cases. Second-look arthroscopies revealed good, congruent, gliding surfaces of the transplants and acceptable fibrocartilage coverage of donor sites in 16 patients and degenerative changes of the transplants in 5 cases. Histological evaluation revealed good graft incorporation in all 11 cases. Two infections and 3 deep venous thromboses occurred. Conclusion: Despite a higher rate of preoperative osteoarthritic changes in the athletic patients, clinical outcomes of mosaicplasty in this group demonstrated a success rate similar to that of less athletic patients. Higher motivation resulted in better subjective evaluation. Slight deterioration in results occurred during the 9.6-year follow-up; thus, autologous osteochondral mosaicplasty may be a useful alternative for the treatment of 1.0- to 4.0-cm2 focal chondral and osteochondral lesions in competitive athletes.
Effect of Electron Beam Irradiation on Biomechanical Properties of Patellar Tendon Allografts in Anterior Cruciate Ligament Reconstruction
Authors: Hoburg Arnd T. , Keshlaf Salahedeen , Schmidt Tanja , Smith Mark , Gohs Uwe , Perka Carsten , Pruss Axel , Scheffler Sven 
Published: April 2010

Background: Sterilization of anterior cruciate ligament (ACL) allografts is an important prerequisite to prevent disease transmission. However, mechanical tissue properties are compromised by most current sterilization procedures, so that uncompromised sterilization of allografts is difficult to achieve. Hypothesis/Purpose: The aim of this study was to evaluate the effect of the novel electron beam sterilization procedure on the biomechanical properties of human patellar tendon allografts at various irradiation dosages. Electron beam sterilization may be an appropriate alternative to gamma sterilization. Study Design: Controlled laboratory study. Methods: Thirty-two human 10-mm wide bone-patellar tendon-bone grafts were randomized into 4 groups of sterilization with 15, 25, or 34 kGy of electron beam irradiation, respectively. The grafts’ biomechanical properties were evaluated at time zero. Unsterilized grafts functioned as controls. Biomechanical properties were analyzed during cyclic and load-to-failure testing. Results: Strain and cyclic elongation response showed no significant differences between the groups. Electron beam irradiation had no significant effect on stiffness and failure load with the exception of 34 kGy, which resulted in a significant decrease in failure load (1300.6 ± 229.2 N) compared with unsterilized grafts (1630.5 ± 331.1 N). Conclusion: This study showed that electron beam might be an appropriate alternative in sterilization of patellar tendon allografts with minimal effect on mechanical properties of tendon grafts in vitro. Future studies will have to evaluate the effect of the process on the biological properties of allografts in vitro and in vivo. Clinical Relevance: Terminal sterilization of patellar tendon allografts with electron beam irradiation can ensure higher safety of transplanted grafts and hence improve patient safety and acceptance.
Dynamic Radiologic Evaluation of Horizontal Instability in Acute Acromioclavicular Joint Dislocations
Authors: Tauber Mark , Koller Heiko , Hitzl Wolfgang , Resch Herbert 
Published: April 2010

Background: Biplane radiologic evaluation is indispensable for the correct diagnosis of acute acromioclavicular (AC) joint injuries. Thus far, no functional radiographic techniques have been quantified to evaluate horizontal instability in acute AC joint dislocations. Hypothesis: Supine dynamic axillary lateral shoulder views detect horizontal instability of the distal clavicle in patients with acute AC joint dislocations. Study Design: Cohort study (Diagnosis); Level of evidence, 2. Methods: Twenty-five consecutive patients with a mean age of 39 ± 14 years with acute AC joint injury underwent biplane radiologic evaluation, including a conventional Zanca view and an axillary lateral view in a sitting position. In addition, supine axillary lateral views with the arm in 90° of abduction and 60° of flexion and extension were taken to evaluate the horizontal dynamics of the distal clavicle. The gleno-acromio-clavicular angle (GACA) was introduced and used to quantify the horizontal clavicular dynamics in terms of angle differences. The unaffected shoulders served as the control group. Results: Superior dislocation of the lateral clavicle in the Zanca view was classified as Rockwood type II in 7 patients, type III in 15, and type V in 3. The axillary lateral view in a sitting position showed posterior dislocation of the distal clavicle in 8 patients (Rockwood type IV injury). Dynamic radiologic evaluation revealed an average GACA difference between the neutral and anterior position of the arm of 7.1° ± 5.5° for the unaffected shoulder. In the injured AC joints, 11 patients showed no radiologic evidence of horizontal instability (group A) with a GACA difference of 7.1° ± 4.8°. Increased anteroposterior translation was evident in 14 patients (group B) with a GACA difference of 30.3° ± 14.3° ( P < .001). Conclusion: Functional axillary radiologic evaluation seems to represent a simple imaging tool to reveal dynamic horizontal instability. Clinical Relevance: Horizontal instability of the distal clavicle in acute AC joint injuries represents an indication for surgical treatment. Dynamic axillary radiologic evaluation may detect previously missed unstable injuries. This evaluation might be relevant when deciding on surgical AC joint stabilization.
Exploiting the mevalonate pathway to distinguish statin-sensitive multiple myeloma
Authors: Clendening James W. , Pandyra Aleksandra , Li Zhihua , Boutros Paul C. , Martirosyan Anna , Lehner Richard , Jurisica Igor , Trudel Suzanne , Penn Linda Z. 
Published: April 2010

AbstractStatin inhibitors, used to control hypercholesterolemia, trigger apoptosis of hematologic tumor cells and therefore have immediate potential as anticancer agents. Evaluations of statins in acute myelogenous leukemia and multiple myeloma have shown that statin efficacy is mixed, with only a subset of tumor cells being highly responsive. Our goal was to distinguish molecular features of statin-sensitive and -insensitive myeloma cells and gain insight into potential predictive markers. We show that dysregulation of the mevalonate pathway is a key determinant of sensitivity to statin-induced apoptosis in multiple myeloma. In sensitive cells, the classic feedback response to statin exposure is lost. This results in deficient up-regulation of 2 isoforms of hydroxymethylglutaryl coenzyme A reductase: the rate-limiting enzyme of the mevalonate pathway and hydroxymethylglutaryl coenzyme A synthase 1. To ascertain the clinical utility of these findings, we demonstrate that a subset of primary myeloma cells is sensitive to statins and that monitoring dysregulation of the mevalonate pathway may distinguish these cancers. We also show statins are highly effective and well tolerated in an orthotopic model of myeloma using cells harboring this dysregulation. This determinant of sensitivity further provides molecular rationale for the significant therapeutic index of statins on these tumor cells.
Deletion of proapoptotic Puma selectively protects hematopoietic stem and progenitor cells against high-dose radiation
Authors: Shao Lijian , Sun Yan , Zhang Zhonghui , Feng Wei , Gao Yongxing , Cai Zailong , Wang Zack Z. , Look A. Thomas , Wu Wen-Shu 
Published: April 2010

Abstract
Bone marrow injury is a major adverse side effect of radiation and chemotherapy. Attempts to limit such damage are warranted, but their success requires a better understanding of how radiation and anticancer drugs harm the bone marrow. Here, we report one pivotal role of the BH3-only protein Puma in the radiosensitivity of hematopoietic stem cells (HSCs) and hematopoietic progenitor cells (HPCs). Puma deficiency in mice confers resistance to high-dose radiation in a hematopoietic cell–autonomous manner. Unexpectedly, loss of one Puma allele is sufficient to confer mice radioresistance. Interestingly, null mutation in Puma protects both primitive and differentiated hematopoietic cells from damage caused by low-dose radiation but selectively protects HSCs and HPCs against high-dose radiation, thereby accelerating hematopoietic regeneration. Consistent with these findings, Puma is required for radiation-induced apoptosis in HSCs and HPCs, and Puma is selectively induced by irradiation in primitive hematopoietic cells, and this induction is impaired in Puma-heterozygous cells. Together, our data indicate that selective targeting of p53 downstream apoptotic targets may represent a novel strategy to protecting HSCs and HPCs in patients undergoing intensive cancer radiotherapy and chemotherapy.
Platelets regulate lymphatic vascular development through CLEC-2–SLP-76 signaling
Authors: Bertozzi Cara C. , Schmaier Alec A. , Mericko Patricia , Hess Paul R. , Zou Zhiying , Chen Mei , Chen Chiu-Yu , Xu Bin , Lu Min-min , Zhou Diane , Sebzda Eric , Santore Matthew T. , Merianos Demetri J. , Stadtfeld Matthias , Flake Alan W. , Graf Thomas , Skoda Radek , Maltzman Jonathan S. , Koretzky Gary A. , Kahn Mark L. 
Published: April 2010

AbstractAlthough platelets appear by embryonic day 10.5 in the developing mouse, an embryonic role for these cells has not been identified. The SYK–SLP-76 signaling pathway is required in blood cells to regulate embryonic blood-lymphatic vascular separation, but the cell type and molecular mechanism underlying this regulatory pathway are not known. In the present study we demonstrate that platelets regulate lymphatic vascular development by directly interacting with lymphatic endothelial cells through C-type lectin-like receptor 2 (CLEC-2) receptors. PODOPLANIN (PDPN), a transmembrane protein expressed on the surface of lymphatic endothelial cells, is required in nonhematopoietic cells for blood-lymphatic separation. Genetic loss of the PDPN receptor CLEC-2 ablates PDPN binding by platelets and confers embryonic lymphatic vascular defects like those seen in animals lacking PDPN or SLP-76. Platelet factor 4-Cre–mediated deletion of Slp-76 is sufficient to confer lymphatic vascular defects, identifying platelets as the cell type in which SLP-76 signaling is required to regulate lymphatic vascular development. Consistent with these genetic findings, we observe SLP-76–dependent platelet aggregate formation on the surface of lymphatic endothelial cells in vivo and ex vivo. These studies identify a nonhemostatic pathway in which platelet CLEC-2 receptors bind lymphatic endothelial PDPN and activate SLP-76 signaling to regulate embryonic vascular development.