bluuebunny/crossref_metadata_2025_split huggingface dataset:
Impairment of Dilator Responses of Cerebral Arterioles During Diabetes Mellitus
Authors: Kitayama Jiro , Faraci Frank M. , Gunnett Carol A. , Heistad Donald D. 
Published: June 2006

Background and Purpose—During diabetes, expression of inducible nitric oxide synthase (iNOS) plays an important role in the development of endothelial dysfunction in extracranial blood vessels. Progression of vascular dysfunction after the onset of diabetes differs among vascular beds. In this study, the effects of hyperglycemia/diabetes on vasomotor function were examined in cerebral arterioles at 2 different times in control and iNOS-deficient mice and compared with the effects on carotid arteries.Methods—Streptozotocin (150 mg/kg IP) was given to induce diabetes. The diameter of cerebral arterioles was measured through a cranial window in diabetic and nondiabetic mice in vivo. Vasomotor function of the carotid artery was examined in vitro.Results—In diabetic mice, responses of the cerebral arterioles to acetylcholine (1 μmol/L) were normal after 3 weeks of diabetes but were significantly impaired after 5 to 6 weeks of diabetes (4±1% [mean±SEM] increase in diameter) compared with control mice (14±1;P=0.0002). Responses to sodium nitroprusside were similar in diabetic and nondiabetic mice at both time points. In contrast, the vasomotor function of the carotid artery was not affected after 5 to 6 weeks of diabetes. In diabetic iNOS-deficient mice, cerebral arteriolar vasomotor function was not impaired, even after 4 months of diabetes.Conclusions—During diabetes, endothelial dysfunction of cerebral arterioles requires expression of iNOS and develops earlier than in carotid arteries.
The Unintended Consequences of a Standardized Knowledge Base in Advancing Educational Leadership Preparation
Authors: English Fenwick W. 
Published: June 2006

Background: The quest for a “knowledge base” in educational administration resulting in the construction of national standards for preparing school leaders has brought with it an unexpected downside. Purpose: It is argued that instead of raising the bar for preparing educational leaders, the standards have lowered them, first by embracing only a limited set of the actual responsibilities of school leaders, resulting in programmatic reductionism, and permitting the licensing of school leaders at sites outside the purview of the university, by definition a form of deprofessionalization. The standards also assume the existence of a static knowledge base tied to a static social system. Current skill sets contained in the standards are in their essence antichange and antidemocratic. Conclusions: The major assumption that must be questioned is the notion or requirement of a stable knowledge base that is a political necessity in accreditation and licensing practices but the hallmark of a dead field of studies empirically.
Catastrophic Cervical Spine Injuries in High School and College Football Players
Authors: Boden Barry P. , Tacchetti Robin L. , Cantu Robert C. , Knowles Sarah B. , Mueller Frederick O. 
Published: July 2006

Background Catastrophic cervical spine injuries in football are rare but tragic events. Purpose To update the incidence of catastrophic cervical injuries in scholastic football players and identify new injury patterns. Study Design Descriptive epidemiology study. Methods The authors retrospectively reviewed 196 incidents of catastrophic high school and collegiate football injuries reported to the National Center for Catastrophic Sports Injury Research during 13 academic years (September 1989 through June 2002). Results There were 15.08 direct catastrophic cervical spine injuries in scholastic football participants per year, an incidence of 1.10 and 4.72 injuries per 100 000 high school and 100 000 college participants, respectively. Seventy-six athletes had quadriplegia (5.85 per year), 0.50 per 100 000 high school players and 0.82 per 100 000 college players. Spear tackling by players on defense continued to be the predominant mechanism of injury causing quadriplegia. Five athletes had a Brown-Séquard–like syndrome; only 1 made a full recovery. One athlete with Brown-Séquard–like syndrome and permanent neurologic symptoms reported a cervical cord neurapraxia event before the study period. Forty-three athletes (3.31 per year) had diagnosed cervical cord neurapraxia. In addition to hyperflexion and hyperextension injuries, axial forces were found to cause cervical cord neurapraxia. Sixteen of the 43 athletes returned to football after a cervical cord neurapraxia episode, and none of the 16 suffered a permanent quadriplegic event. Nine athletes sustained an isolated injury at the C1 or C2 level, and 7 sustained a combined injury at the C1, or C2 level and at a subaxial level. Conclusion The total number of quadriplegic events for high school and college football players is approximately 6 per year, with a higher incidence at the college level. Cervical cord neurapraxia can be caused by hyperflexion, hyperextension, and axial compression forces. Upper level cervical injuries involving the atlas and axis can occur in football players and may be associated with noncontiguous subaxial injuries.
Translation and Validation of the Dutch Version of the International Knee Documentation Committee Subjective Knee Form
Authors: Haverkamp Daniël , Sierevelt Inger N. , Breugem Stefan J. M. , Lohuis Kim , Blankevoort Leendert , van Dijk C. Niek 
Published: July 2006

Background For knee-related surgery, there is a great demand for internationally useable subjective scoring systems. Before such measurements can be used, they should be translated and validated for the population they are used on. For the Dutch population, only the Western Ontario and McMaster Universities Osteoarthritis Index and Oxford 12 Questionnaire have been validated. However, these scores can only be used regarding osteoarthritis of the knee. In 2001, the International Knee Documentation Committee presented the Subjective Knee Form, which is a knee-specific rather than a disease-specific questionnaire. Study Design Cohort study (diagnosis/symptom prevalence); Level of evidence, 2. Methods The authors describe the translation procedure and validation of the Dutch Subjective Knee Form. After a forward backward translation protocol, the reliability, validity, and content validity were tested. The responses of 145 consecutive knee patients on 2 questionnaires containing the Short Form–36, Western Ontario and McMaster Universities Osteoarthritis Index, Oxford 12 Questionnaire score, a visual analog scale, and the Dutch International Knee Documentation Committee Subjective Knee Form were used. Reliability was tested by measuring the test-retest reliability and internal consistency. Validity was tested by correlating the questionnaire to the other outcome measurements, and content validity was tested by measuring the floor and ceiling effects. Results The reliability proved excellent with an intraclass coefficient of 0.96 for test-retest. Internal consistency was strong (Cronbach [.alpha],. 92). The construct, convergent, and divergent validities were good. The content validity was good; no floor or ceiling effect occurred. Conclusion The validation procedure shows that the Dutch International Knee Documentation Committee Subjective Knee Form is an excellent evaluation instrument for Dutch patients with knee-related injuries.
The Role of the Medial Collateral Ligament and Posteromedial Capsule in Controlling Knee Laxity
Authors: Robinson James R. , Bull Anthony M. J. , deW. Thomas Rhidian R. , Amis Andrew A. 
Published: July 2006

Background The medial aspect of the knee has a complex capsular structure; the biomechanical roles of specific structures are not well understood. Hypothesis The 3 strong stabilizing structures, the superficial and deep medial collateral ligaments and the posteromedial capsule, make distinct contributions to controlling tibiofemoral laxity. Study Design Controlled laboratory study. Methods Changes in knee laxity under anterior-posterior drawer, valgus, and internal-external rotation loads were found by sequential cutting in 18 cadaveric knees. Three cutting sequences allowed the roles of the 3 structures to be seen in isolation and in combination. Some force contributions were also calculated. Results The posteromedial capsule controlled valgus, internal rotation, and posterior drawer in extension, resisting 42% of a 150-N drawer force when the tibia was in internal rotation. The superficial collateral ligament controlled valgus at all angles and was dominant from 30° to 90° of flexion, plus internal rotation in flexion. The deep collateral ligament controlled tibial anterior drawer of the flexed and externally rotated knee and was a secondary restraint to valgus. Conclusion Distinct roles in controlling tibiofemoral laxity have been found for these structures that vary according to knee flexion and tibial rotation. Clinical Relevance The restraining functions demonstrated provide new information about knee stabilization, which may allow better evaluation of structural damage at the medial aspect of the knee.
Induction of antigen-specific tolerance by intrathymic injection of lentiviral vectors
Authors: Marodon Gilles , Fisson Sylvain , Levacher Béatrice , Fabre Monique , Salomon Benoît L. , Klatzmann David 
Published: June 2006

AbstractImmune tolerance to self-antigens is established during lymphocyte differentiation in the thymus, but a simple means to induce antigen-specific tolerance in the thymus is still elusive. We show here that intrathymic injection of a lentiviral vector expressing the hemagglutinin antigen (HA) in TCR-HA transgenic mice resulted in negative selection of HA-specific effector T cells and sustained positive selection of HA-specific regulatory T cells (Tregs). This positive selection increased the number of HA-specific Tregs 10-fold and was comparable with the one observed in TCR-HA transgenic mice crossed with transgenic mice expressing HA under the control of the insulin promoter (Ins-HA). HA expression by radioresistant thymic epithelial cells was sufficient to drive Treg generation. Intrathymic injection of the lentiviral vector also resulted in an enrichment of HA-specific Tregs in peripheral lymphoid organs, which prevented diabetes induced in Ins-HA mice by transfer of HA-specific effector T cells. In this model, HA-specific Tregs inhibited effector T-cell division in pancreatic lymph nodes. Finally, we show that intrathymic injection of a lentiviral vector expressing preproinsulin-2 could reduce the occurrence of spontaneous diabetes in nonobese diabetic mice. Intrathymic gene transfer using lentiviral vectors thus offers new means to manipulate antigen-specific tolerance.
Development of a macrophage-based nanoparticle platform for antiretroviral drug delivery
Authors: Dou Huanyu , Destache Christopher J. , Morehead Justin R. , Mosley R. Lee , Boska Michael D. , Kingsley Jeffrey , Gorantla Santhi , Poluektova Larisa , Nelson Jay A. , Chaubal Mahesh , Werling Jane , Kipp James , Rabinow Barrett E. , Gendelman Howard E. 
Published: June 2006

AbstractComplex dosing regimens, costs, side effects, biodistribution limitations, and variable drug pharmacokinetic patterns have affected the long-term efficacy of antiretroviral medicines. To address these problems, a nanoparticle indinavir (NP-IDV) formulation packaged into carrier bone marrow-derived macrophages (BMMs) was developed. Drug distribution and disease outcomes were assessed in immune-competent and human immunodeficiency virus type 1 (HIV-1)-infected humanized immune-deficient mice, respectively. In the former, NP-IDV formulation contained within BMMs was adoptively transferred. After a single administration, single-photon emission computed tomography, histology, and reverse-phase-high-performance liquid chromatography (RP-HPLC) demonstrated robust lung, liver, and spleen BMMs and drug distribution. Tissue and sera IDV levels were greater than or equal to 50 μM for 2 weeks. NP-IDV-BMMs administered to HIV-1-challenged humanized mice revealed reduced numbers of virus-infected cells in plasma, lymph nodes, spleen, liver, and lung, as well as, CD4+ T-cell protection. We conclude that a single dose of NP-IDV, using BMMs as a carrier, is effective and warrants consideration for human testing.
BCL11B participates in the activation of IL2 gene expression in CD4+ T lymphocytes
Authors: Cismasiu Valeriu B. , Ghanta Sailaja , Duque Javier , Albu Diana I. , Chen Hong-Mei , Kasturi Rohini , Avram Dorina 
Published: June 2006

AbstractBCL11A and BCL11B are transcriptional regulators important for lymphopoiesis and previously associated with hematopoietic malignancies. Ablation of the mouse Bcl11b locus results in failure to generate double-positive thymocytes, implicating a critical role of Bcl11b in T-cell development. However, BCL11B is also expressed in CD4+ T lymphocytes, both in resting and activated states. Here we show both in transformed and primary CD4+ T cells that BCL11B participates in the control of the interleukin-2 (IL2) gene expression following activation through T-cell receptor (TCR). BCL11B augments expression from the IL2 promoter through direct binding to the US1 site. In addition, BCL11B associates with the p300 coactivator in CD4+ T cells activated through TCR, which may account for its transcriptional activation function. These results provide the first evidence that BCL11B, originally described as a transcriptional repressor, activates transcription of a target gene in the context of T-cell activation.
Dyspnoea and hypoxaemia after lung surgery: the role of interatrial right-to-left shunt
Authors: Marini C. , Miniati M. , Ambrosino N. , Formichi B. , Tonelli L. , Di Ricco G. , Michelassi C. , Giusti S. , Spadoni I. 
Published: July 2006

After lung surgery, some patients complain of unexplained increased dyspnoea associated with hypoxaemia. This clinical presentation may be due to an interatrial right-to-left shunt despite normal right heart pressure. Some of these patients show postural dependency of hypoxaemia, whereas others do not.In this article, the pathogenesis and mechanisms involved in this post-surgical complication are discussed, and the techniques used for confirmation and localisation of shunt are reported.An invasive technique, such as right heart catheterisation with angiography, was often used in the past as the diagnostic procedure for the visualisation of interatrial shunt. As to noninvasive techniques, a perfusion lung scan may be used as the first approach as it may detect the effect of the right-to-left shunt by visualising an extrapulmonary distribution of the radioactive tracer. The 100% oxygen breathing test could also be used to quantify the amount of right-to-left shunt. Particular emphasis is given to newer imaging modalities, such as transoesophageal echocardiography, which is minimally invasive but highly sensitive in clearly visualising the atrial septum anatomy.Finally, the approch to closure of the foramen ovale or atrial septal defect is discussed. Open thoracotomy was the traditional approach in the past. Percutaneous closure has now become the most used and effective technique for the repair of the interatrial anatomical malformation.
Place of cryotherapy, brachytherapy and photodynamic therapy in therapeutic bronchoscopy of lung cancers
Authors: Vergnon J-M. , Huber R. M. , Moghissi K. 
Published: July 2006

Cryotherapy, brachytherapy and photodynamic therapy (PDT) are three different methods proposed in the endoluminal treatment of lung cancers. The current article presents an overview of the specific indications and limits of each technique.These three methods were first proposed with palliative intent in inoperable patients with centrally located lung cancers. Now, the best indication is a curative intent in early stage lung cancers.Of the three, cryotherapy is the cheapest method. It induces cell necrosis in a 3-mm radius around the probe, and is suitable for treatment of superficial tumours. However, clinical trials are limited. In contrast, many clinical studies have confirmed the efficacy of PDT in treatment of superficial lung cancers. Brachytherapy can cure more aggressive tumours with deeper invasion into the bronchial wall. Unfortunately, no comparative studies have been published. Each of these methods induces a delayed tumour necrosis, and thus neither is indicated in the treatment of obstructive tumours with acute dyspnoea. In many situations, these methods should be complementary, particularly cryotherapy and brachytherapy or PDT and brachytherapy.The combination of these endoscopic methods with chemotherapy should be widely tested to promote the adjuvant role of the endoscopic methods in the treatment of lung cancers.
Oxidative stress and redox regulation of lung inflammation in COPD
Authors: Rahman I. , Adcock I. M. 
Published: July 2006

Reactive oxygen species, either directly orviathe formation of lipid peroxidation products, may play a role in enhancing inflammation through the activation of stress kinases (c-Jun activated kinase, extracellular signal-regulated kinase, p38) and redox-sensitive transcription factors, such as nuclear factor (NF)-κB and activator protein-1. This results in increased expression of a battery of distinct pro-inflammatory mediators. Oxidative stress activates NF-κB-mediated transcription of pro-inflammatory mediators either through activation of its activating inhibitor of κB-α kinase or the enhanced recruitment and activation of transcriptional co-activators. Enhanced NF-κB-co-activator complex formation results in targeted increases in histone modifications, such as acetylation leading to inflammatory gene expression.Emerging evidence suggests the glutathione redox couple may entail dynamic regulation of protein function by reversible disulphide bond formation on kinases, phosphatases and transcription factors. Oxidative stress also inhibits histone deacetylase activity and in doing so further enhances inflammatory gene expression and may attenuate glucocorticoid sensitivity.The antioxidant/anti-inflammatory effects of thiol molecules (glutathione,N-acetyl-L-cysteine andN-acystelyn, erdosteine), dietary polyphenols (curcumin-diferuloylmethane, cathechins/quercetin and reserveratol), specific spin traps, such as α-phenyl-N-tert-butyl nitrone, a catalytic antioxidant (extracellular superoxide dismutase (SOD) mimetic, SOD mimetic M40419 and SOD, and catalase manganic salen compound, eukarion-8), porphyrins (AEOL 10150 and AEOL 10113) and theophylline have all been shown to play a role in either controlling NF-κB activation or affecting histone modifications with subsequent effects on inflammatory gene expression in lung epithelial cells.Thus, oxidative stress regulates both key signal transduction pathways and histone modifications involved in lung inflammation. Various approaches to enhance lung antioxidant capacity and clinical trials of antioxidant compounds in chronic obstructive pulmonary disease are also discussed.
Positional hyperventilation-induced hypoxaemia in pectus excavatum
Authors: Wallaert B. , Cavestri B. , Fournier C. , Nevière R. , Aguilaniu B. 
Published: July 2006

The presented case is of a young male (aged 19 yrs) with a pectus excavatum who showed significant exercise intolerance, despite normal pulmonary function at rest, including carbon monoxide diffusing capacity. Clinical exercise testing led to a strong suspicion of a right-to-left shunt due to an abnormally wide alveolo–arterial oxygen gradient (26.4 kPa) at peak oxygen uptake, with severe arterial hypoxaemia (arterial oxygen tension 12.54 kPa).A right-to-left shunt was confirmed by transoesophageal echocardiography demonstrating a permeable foramen ovale, despite normal right heart pressures. The right-to-left venous flow was mainly dependent on the upright body position and the deep inspiration. Indeed,i.v.dobutamine infusion to selectively affect cardiac output and hyperventilation induced by tidal volume expansion at constant breathing rate in the supine position did not result in arterial oxygen desaturation or shunting. Closure of the foramen ovale through atrial umbrella placement dramatically improved clinical and physiological abnormalities.This observation demonstrates that a hyperventilatory manoeuvre in the upright position is able to detect a permeable foramen ovale favouring flow in the inferior vena cava in the direction of the abnormal pre-existing atrial channel in a patient with a pectus excavatum.
Pharmacological strategies for self-management of asthma exacerbations: Table 1—
Authors: Reddel H. K. , Barnes D. J. 
Published: July 2006

Written action plans are effective within asthma self-management, but there are few guidelines about the specific medication adjustments which can be recommended for self-treatment of exacerbations.This review examines pharmacological strategies for self-management of asthma exacerbations in adults, including those for inhaled corticosteroid/long-acting β2-agonist (ICS/LABA) users.Oral corticosteroids are well-established in clinical practice and clinical trials for the treatment of severe exacerbations, including during combination therapy. Evidence supports 7–10 days treatment, with no need to taper except to reduce side-effects. Doubling the dose of ICS is not effective. Several studies have shown benefit from high-dose ICS (2,400–4,000 µg beclomethasone equivalent) for 1–2 weeks. This may be achieved by adding a high-dose ICS inhaler to maintenance ICS or ICS/LABA therapy. There is inconclusive evidence about acutely increasing the dose of maintenance budesonide/formoterol for exacerbations, and no studies of this approach with fluticasone/salmeterol. For patients taking maintenance budesonide/formoterol, use of the same medication as-needed reduces exacerbations. Short-acting β2-agonists are still effective in producing bronchodilation during combination therapy; however, a higher dose may be required.There is a need for further studies to clarify remaining issues about self-management of asthma exacerbations, particularly with regard to side-effects of treatment and patient acceptability.
Dendritic cell derived-exosomes: biology and clinical implementations
Authors: Chaput Nathalie , Flament Caroline , Viaud Sophie , Taieb Julien , Roux Stephan , Spatz Alain , André Fabrice , LePecq Jean-Bernard , Boussac Muriel , Garin Jérôme , Amigorena Sebastian , Théry Clotilde , Zitvogel Laurence 
Published: June 2006

Abstract
Exosomes are nanometer-sized membrane vesicles invaginating from multivesicular bodies and secreted from different cell types. They represent an “in vitro” discovery, but vesicles with the hallmarks of exosomes are present in vivo in germinal centers and biological fluids. Their protein and lipid composition is unique and could account for their expanding functions such as eradication of obsolete proteins, antigen presentation, or “Trojan horses” for viruses or prions. The potential of dendritic cell-derived exosomes (Dex) as cell-free cancer vaccines is addressed in this review. Lessons learned from the pioneering clinical trials allowed reassessment of the priming capacities of Dex in preclinical models, optimizing clinical protocols, and delineating novel, biological features of Dex in cancer patients.