bluuebunny/crossref_metadata_2025_split huggingface dataset:
Work and Vocational Psychology: Theory, Research, and Applications
Authors: Fouad Nadya A. 
Published: August 2006

Abstract Work is integral to human functioning, and all psychologists need to understand the role of work in people's lives. Understanding factors influencing work choices and helping individuals effectively make career decisions is the focus of vocational psychologists. However, external changes, such as shifts in the economy and labor force, as well as initiatives within the field are challenging the assumptions within vocational psychology. This chapter reviews the empirical work since 1995 in four areas: (a) what factors influence career choices, (b) how people make career decisions, (c) how context influences career choices, and (d) effective interventions for help with the first three questions. The review focuses first on vocational psychology's rich tradition of theoretically driven research, and then discusses research in career development that crosses a number of theoretical approaches, and finally identifies the assumptions in the field and questions for future examination.
Induction of Monocytic Tissue Factor Expression After Rewarming From Hypothermia In Vivo Is Counteracted by Heat Shock in c-Jun–Dependent Manner
Authors: Egorina Elena M. , Sovershaev Mikhail A. , Kondratiev Timofei V. , Olsen Jan O. , Tveita Torkjel , Østerud Bjarne 
Published: August 2006

Objective—Triggering of tissue factor (TF)-mediated blood coagulation leads to the development of disseminated intravascular coagulation during rewarming from hypothermia. We studied post-rewarming TF levels, activity, and surface redistribution, along with the regulation of TF gene transcription in mononuclear cells (MNCs) obtained from an in vivo rat model.Methods and Results—Rewarming after a 5-hour episode of 15°C hypothermia caused an increase in TF activity, protein levels, and externalization of TF antigen in rat MNCs. This was accompanied by a dramatic elevation of c-Jun and JNK phosphorylation, and the absence of EGR-1 and NF-κB activation. To search for a stimulus to counteract c-Jun–mediated induction of TF activity in MNCs from rewarmed rats, we applied heat shock pretreatment one day before the hypothermia/rewarming experiment. This restored post-rewarming TF activity, protein levels, and surface-to-total TF ratio in rat MNCs to normothermic levels. Furthermore, in heat shock-pretreated animals, rewarming failed to increase phosphorylated c-Jun and JNK levels. We attribute this to the profound overexpression of heat shock protein 70 and inhibition of JNK.Conclusions—MNCs respond to rewarming from hypothermia by an induction of active TF antigen. This effect is dependent on c-Jun activation and is abolished by heat shock pretreatment.
Interaction of Arch Type and Footwear on Running Mechanics
Authors: Butler Robert J. , Davis Irene S. , Hamill Joseph 
Published: August 2006

Background Running shoes are designed to accommodate various arch types to reduce the risk of lower extremity injuries sustained during running. Yet little is known about the biomechanical changes of running in the recommended footwear that may allow for a reduction in injuries. Purpose To evaluate the effects of motion control and cushion trainer shoes on running mechanics in low-and high-arched runners. Study Design Controlled laboratory study. Methods Twenty high-arched and 20 low-arched recreational runners (&gt;10 miles per week) were recruited for the study. Three-dimensional kinematic and kinetics were collected as subjects ran at 3.5 ms-1 ± 5% along a 25-m runway. The motion control shoe evaluated was the New Balance 1122, and the cushioning shoe evaluated was the New Balance 1022. Repeated-measures analyses of variance were used to determine if low- and high-arched runners responded differently to motion control and cushion trainer shoes. Results A significant interaction was observed in the instantaneous loading rate such that the low-arched runners had a lower instantaneous loading rate in the motion control condition, and the high-arched runners had a lower instantaneous loading rate in the cushion trainer condition. Significant main effects for shoe were observed for peak positive tibial acceleration, peak-to-peak tibial acceleration, mean loading rate, peak eversion, and eversion excursion. Conclusion These results suggest that motion control shoes control rearfoot motion better than do cushion trainer shoes. In addition, cushion trainer shoes attenuate shock better than motion control shoes do. However, with the exception of instantaneous loading rate, these benefits do not differ between arch type. Clinical Relevance Running footwear recommendations should be based on an individual's running mechanics. If a mechanical analysis is not available, footwear recommendations can be based empirically on the individual's arch type.
Corticosteroids Reduce the Tensile Strength of Isolated Collagen Fascicles
Authors: Haraldsson Bjarki Thor , Langberg Henning , Aagaard Per , Zuurmond Anne-Marie , van El Benno , DeGroot Jeroen , Kjær Michael , Magnusson S. Peter 
Published: August 2006

Background Overuse tendon injuries are frequent. Corticosteroid injections are commonly used as treatment, although their direct effects on the material properties of the tendon are poorly understood. Purpose To examine the influence of corticosteroids on the tensile strength of isolated collagen fascicles. Study Design Controlled laboratory study. Methods Single strands (300-500 [.mu]m) of rat-tail collagen fascicles were incubated in either high (1 mL of 40 mgmL-1 mixed with 0.5 mL saline 9%) or low (1 mL of 40 mgmL-1 mixed with 2 mL saline 9%) concentration of methylprednisolone acetate (Depomedrol) for 3 or 7 days, while the control segment from the same fascicle was kept in saline (N = 64). After the incubation period, the fascicles underwent displacement to failure in a mechanical test rig at 0.13 mm/s, and thereafter hydroxylysyl pyridinoline and lysyl pyridinoline cross-link content was evaluated in a high-performance liquid chromatography system. Data for each group were analyzed with a 2-way analysis of variance (time × incubation) for ultimate stress (mean ± standard deviation). Results In the high-concentration groups, strength was reduced after 3 (16.6 ± 4.6 MPa) and 7 (8.6 ± 1.7 MPa) days compared to the controls (30.2 ± 5.0 MPa and 25.6 ± 4.6 MPa, respectively; P <. 05). In the low-concentration groups, strength was reduced after 3 (12.0 ± 3.1 MPa) and 7 days (10.9 ± 2.5 MPa) compared to the controls (31.5 ± 5.0 MPa and 32.4 ± 5.6 MPa, respectively; P <. 05). The amount of cross-linking was unaffected by the intervention. Conclusion Data show that the tensile strength of isolated fascicles is markedly reduced after 3-and 7-day incubation in both high and low concentration of corticosteroids, although the observed effect on whole tendon remains unknown. Clinical Relevance Corticosteroids may weaken specific regions of the injected tendon and leave it more prone to rupture. This weakening effect is manifested in the individual collagen fascicles that constitute the tendon.
Long–term Results of Arthroscopic Bankart Repair with a Bioabsorbable Tack
Authors: Marquardt Björn , Witt Kai–Axel , Götze Christian , Liem Dennis , Steinbeck Jörn , Pötzl Wolfgang 
Published: August 2006

Background Short-term to midterm data are available on arthroscopic shoulder stabilization using bioabsorbable tacks or suture anchors. It remains unknown whether these techniques can equal the success of open Bankart repair in the long term. Purpose To assess the long-term outcome of arthroscopic Bankart repair using bioabsorbable tacks in patients with traumatic anterior shoulder instability with a minimum follow-up of 7 years. Study Design Case series; Level of evidence, 4. Methods Treatment outcomes were determined prospectively according to the Rowe score and retrospectively according to the Constant and American Shoulder and Elbow Surgeons scores. Included in this study were 18 consecutive patients with a mean age of 26.8 years (range, 16-62 years) who underwent arthroscopic Bankart repair using bioabsorbable tacks for traumatic anterior shoulder instability. The study group consisted of 14 male and 4 female patients. The mean follow-up was 8.7 years (range, 7.0-9.8 years). Results One patient had recurrent dislocations requiring further surgery, for an overall failure rate of 5.6%. An additional patient had 1 traumatic subluxation episode within the first postoperative year that did not recur. According to the Rowe score, which increased to 90.3 (17.8) from 32.8 (8.3) points preoperatively, 15 patients (83.3%) achieved a good or excellent result. The mean Constant score was 91.3 (SD, 6.9) points, and the mean American Shoulder and Elbow Surgeons score was 92.1 (SD, 6.9) points postoperatively. A return to the preinjury level of sports competition was reported by 64% of patients. No signs of synovitis occurred in any patient postoperatively. Conclusion Arthroscopic Bankart repair for the treatment of recurrent traumatic anterior shoulder instability repair using bioabsorbable tacks offers reliable results with respect to failure rate, range of motion, and shoulder function during a minimum follow- up of 7.0 years. In contrast to previous reports on arthroscopic Bankart repair, results did not deteriorate during follow-up.
Medial Ulnar Collateral Ligament Reconstruction of the Elbow in Throwing Athletes
Authors: Dodson Christopher C. , Thomas Adrian , Dines Joshua S. , Nho Shane J. , Williams Riley J. , Altchek David W. 
Published: August 2006

Background Medial ulnar collateral ligament insufficiency of the elbow can be a devastating injury in the throwing athlete. Reconstruction of the medial ulnar collateral ligament was initially described by Jobe and associates; good clinical results have been described after this procedure. The authors' experience with this technique raised several concerns, and thus the “docking” procedure was developed as an alternative method for medial ulnar collateral ligament reconstruction of the elbow. The early results of the docking technique were good. The authors wish to investigate the intermediate-term clinical results of this method in a large group of athletes. Hypothesis The docking technique can return overhead-throwing athletes to sport with minimal perioperative morbidity. Study Design Case series; Level of evidence, 4. Methods During a 3-year period, 100 consecutive overhead-throwing athletes were treated with surgical reconstruction using the docking technique. The inclusion criteria were as follows: (1) a history of medial elbow pain that prevented throwing, (2) a preoperative standard noncontrast magnetic resonance image demonstrating medial ulnar collateral ligament injury, (3) clinically apparent medial ulnar collateral ligament insufficiency, and (4) an overhead-throwing athlete. At the time of surgery, all patients underwent routine arthroscopic assessment. The ulnar nerve was transposed in 22 cases. The mean follow-up was 36 months (range, 24-60 months). Results Ninety of 100 (90%) patients were able to compete at the same or a higher level than before medial ulnar collateral ligament injury for more than 12 months as noted at the follow-up interval; 7 patients were able to compete at a lower level. Only 3 patients suffered postoperative complications. Conclusion The docking technique reliably returns athletes to competitive throwing with a low perioperative morbidity.
Cis and trans regulation of hepcidin expression by upstream stimulatory factor
Authors: Bayele Henry K. , McArdle Harry , Srai Surjit K.S. 
Published: August 2006

AbstractHepcidin is the presumed negative regulator of systemic iron levels; its expression is induced in iron overload, infection, and inflammation, and by cytokines, but is suppressed in hypoxia and anemia. Although the gene is exquisitely sensitive to changes in iron status in vivo, its mRNA is devoid of prototypical iron-response elements, and it is therefore not obvious how it may be regulated by iron flux. The multiplicity of effectors of its expression also suggests that the transcriptional circuitry controlling the gene may be very complex indeed. In delineating enhancer elements within both the human and mouse hepcidin gene promoters, we show here that members of the basic helix-loop-helix leucine zipper (bHLH-ZIP) family of transcriptional regulators control hepcidin expression. The upstream stimulatory factor 2 (USF2), previously linked to hepcidin through gene ablation in inbred mice, appears to exert a polar or cis-acting effect, while USF1 may act in trans to control hepcidin expression. In mice, we found variation in expression of both hepcidin genes, driven by these transcription factors. In addition, c-Myc and Max synergize to control the expression of this hormone, supporting previous findings for the role of this couple in regulating iron metabolism. Transcriptional activation by both USF1/USF2 and c-Myc/Max heterodimers occurs through E-boxes within the promoter. Site-directed mutagenesis of these elements rendered the promoter unresponsive to USF1/USF2 or c-Myc/Max. Dominant-negative mutants of USF1 and USF2 reciprocally attenuated promoter transactivation by both wild-type USF1 and USF2. Promoter occupancy by the transcription factors was confirmed by DNA-binding and chromatin immunoprecipitation assays. Taken together, it would appear that synergy between these members of the bHLH-ZIP family of transcriptional regulators may subserve an important role in iron metabolism as well as other pathways in which hepcidin may be involved.
Growth factor receptors as regulators of hematopoiesis
Authors: Weinreich Michael A. , Lintmaer Ingrid , Wang Linlin , Liggitt H. Denny , Harkey Michael A. , Blau C. Anthony 
Published: August 2006

AbstractNearly 15 years have elapsed since the US Food and Drug Administration last approved a major new hematopoietic cytokine. Promiscuous binding to multiple receptors, or to receptors expressed by multiple tissues, reduces growth factor specificity and promotes side effects. Here we show that hematopoiesis can be differentially regulated using receptors rather than ligands. Conditional derivatives of both fibroblast growth factor receptor-1 (F36VFGFR1) and the thrombopoietin receptor (F36VMpl) induced a sustained expansion of mouse marrow cells ex vivo, and erythroid cells in vivo. Only F36VFGFR1 could support the ex vivo expansion of short-term repopulating hematopoietic stem cells (HSCs), the ex vivo survival of long-term repopulating HSCs, and the prolonged in vivo expansion of granulocytes, monocytes, and platelets. Only F36VMpl induced a response sufficiently rapid to accelerate recovery from radiation-induced anemia. These results establish receptors as a new class of hematopoietic regulators possessing activities unobtainable with growth factors.
Phase 1 clinical results with tandutinib (MLN518), a novel FLT3 antagonist, in patients with acute myelogenous leukemia or high-risk myelodysplastic syndrome: safety, pharmacokinetics, and pharmacodynamics
Authors: DeAngelo Daniel J. , Stone Richard M. , Heaney Mark L. , Nimer Stephen D. , Paquette Ronald L. , Klisovic Rebecca B. , Caligiuri Michael A. , Cooper Michael R. , Lecerf Jean-Michel , Karol Michael D. , Sheng Shihong , Holford Nick , Curtin Peter T. , Druker Brian J. , Heinrich Michael C. 
Published: August 2006

AbstractTandutinib (MLN518/CT53518) is a novel quinazoline-based inhibitor of the type III receptor tyrosine kinases: FMS-like tyrosine kinase 3 (FLT3), platelet-derived growth factor receptor (PDGFR), and KIT. Because of the correlation between FLT3 internal tandem duplication (ITD) mutations and poor prognosis in acute myelogenous leukemia (AML), we conducted a phase 1 trial of tandutinib in 40 patients with either AML or high-risk myelodysplastic syndrome (MDS). Tandutinib was given orally in doses ranging from 50 mg to 700 mg twice daily The principal dose-limiting toxicity (DLT) of tandutinib was reversible generalized muscular weakness, fatigue, or both, occurring at doses of 525 mg and 700 mg twice daily. Tandutinib's pharmacokinetics were characterized by slow elimination, with achievement of steady-state plasma concentrations requiring greater than 1 week of dosing. Western blotting showed that tandutinib inhibited phosphorylation of FLT3 in circulating leukemic blasts. Eight patients had FLT3-ITD mutations; 5 of these were evaluable for assessment of tandutinib's antileukemic effect. Two of the 5 patients, treated at 525 mg and 700 mg twice daily, showed evidence of antileukemic activity, with decreases in both peripheral and bone marrow blasts. Tandutinib at the MTD (525 mg twice daily) should be evaluated more extensively in patients with AML with FLT3-ITD mutations to better define its antileukemic activity.
The tryptophan catabolite l-kynurenine inhibits the surface expression of NKp46- and NKG2D-activating receptors and regulates NK-cell function
Authors: Chiesa Mariella Della , Carlomagno Simona , Frumento Guido , Balsamo Mirna , Cantoni Claudia , Conte Romana , Moretta Lorenzo , Moretta Alessandro , Vitale Massimo 
Published: August 2006

AbstractTryptophan (Trp) catabolism mediated by indoleamine 2,3-dioxygenase (IDO) plays a central role in the regulation of T-cell–mediated immune responses. In this study, we also demonstrate that natural killer (NK)–cell function can be influenced by IDO. Indeed, l-kynurenine, a Trp-derived catabolite resulting from IDO activity, was found to prevent the cytokine-mediated up-regulation of the expression and function of specific triggering receptors responsible for the induction of NK-cell–mediated killing. The effect of l-kynurenine appears to be restricted to NKp46 and NKG2D, while it does not affect other surface receptors such as NKp30 or CD16. As a consequence, l-kynurenine–treated NK cells display impaired ability to kill target cells recognized via NKp46 and NKG2D. Instead, they maintain the ability to kill targets, such as dendritic cells (DCs), that are mainly recognized via the NKp30 receptor. The effect of l-kynurenine, which is effective at both the transcriptional and the protein level, can be reverted, since NK cells were found to recover their functional competence after washing.
Cytotoxic T cells generated against heteroclitic peptides kill primary tumor cells independent of the binding affinity of the native tumor antigen peptide
Authors: Zirlik Katja Mauerer , Zahrieh David , Neuberg Donna , Gribben John G. 
Published: August 2006

AbstractHeteroclitic peptide modifications increase immunogenicity, allowing generation of cytotoxic T lymphocytes (CTLs) against weakly immunogenic tumor-associated antigens (TAAs). A critical issue is whether T cells generated against heteroclitic peptides retain the ability to recognize and kill tumor cells expressing the original weak TAAs, and whether there is a lower threshold of binding affinity of the native peptides, below which such CTLs can still kill primary tumor cells. To examine this we used a model examining the ability of native and heteroclitic immunoglobulin (Ig)–derived peptides to generate CTLs that can kill chronic lymphocytic leukemia (CLL) cells. We demonstrate that CTLs generated against heteroclitic peptides have enhanced killing of CD40-activated B cells pulsed with either heteroclitic (P < .001) or native peptide (P = .04) and primary CLL cells (P = .01). The novel finding reported here is that the rate-limiting factor appears to be the ability to generate CTLs and that once generated, CTL lysis of primary tumor cells is independent of the binding affinity of the native peptide. These findings have implications for vaccination strategies in malignancies and are currently being further examined in vivo in murine models.
The mutational spectrum of type 1 von Willebrand disease: results from a Canadian cohort study
Authors: James Paula D. , Notley Colleen , Hegadorn Carol , Leggo Jayne , Tuttle Angie , Tinlin Shawn , Brown Christine , Andrews Chandler , Labelle Andrea , Chirinian Yvette , O'Brien Lee , Othman Maha , Rivard Georges , Rapson Dilys , Hough Christine , Lillicrap David ,   for the Association of Hemophilia Clinic Directors of Canada
Published: August 2006

AbstractIn order to evaluate the changes within the VWF gene that might contribute to the pathogenesis of type 1 von Willebrand disease (VWD), a large multicenter Canadian study was undertaken. We present data from the sequence analysis of the VWF gene in 123 type 1 VWD index cases and their families. We have identified putative mutations within the VWF gene in 63% (n = 78) of index cases, leaving 37% (n = 45) with no identified changes. These changes comprise 50 different putative mutations: 31 (62%) missense mutations, 8 (16%) changes involving the VWF transcriptional regulatory region, 5 (10%) small deletions/insertions, 5 (10%) splicing consensus sequence mutations, and 1 nonsense mutation. Twenty-one of the index cases had more than one putative VWF mutation identified. We were somewhat more likely to identify putative mutations in cases with lower VWF levels, and the contribution of other factors, such as ABO blood group, seems more important in milder cases. Taken as a whole, our data support a complex spectrum of molecular pathology resulting in type 1 VWD. In more severe cases, genetic changes are common within the VWF gene and are highly penetrant. In milder cases, the genetic determinants are more complex and involve factors outside of the VWF gene.
Immunologic and functional evidence for anti–Siglec-9 autoantibodies in intravenous immunoglobulin preparations
Authors: von Gunten Stephan , Schaub Alexander , Vogel Monique , Stadler Beda M. , Miescher Sylvia , Simon Hans-Uwe 
Published: August 2006

AbstractHuman intravenous immunoglobulin (IVIg) preparations are increasingly used for the treatment of autoimmune diseases. Earlier work demonstrated the presence of autoantibodies against Fas in IVIg, suggesting that IVIg might be able to induce caspase-dependent cell death in Fas-sensitive cells. In this study, we demonstrate that sialic acid–binding Ig-like lectin 9 (Siglec) represents a surface molecule on neutrophils that is activated by IVIg, resulting in caspase-dependent and caspase-independent forms of cell death. Neutrophil death was mediated by naturally occurring anti–Siglec-9 autoantibodies present in IVIg. Moreover, the efficacy of IVIg-mediated neutrophil killing was enhanced by the proinflammatory cytokines granulocyte/macrophage colony-stimulating factor (GM-CSF) and interferon-γ (IFN–γ), and this additional cell death required reactive oxygen species (ROSs) but not caspases. Anti– Siglec-9 autoantibody–depleted IVIg failed to induce this caspase-independent neutrophil death. These findings contribute to our understanding of how IVIg preparations exert their immunoregulatory effects under pathologic conditions and may provide a possible explanation for the neutropenia that is sometimes seen in association with IVIg therapy.