bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health-related quality of life is associated with COPD severity: a comparison between the GOLD staging and the BODE index
Authors: Medinas Amorós M , Mas-Tous C , Renom-Sotorra F , Rubí-Ponseti M , Centeno-Flores MJ , Gorriz-Dolz MT 
Published: May 2009

Chronic obstructive pulmonary disease (COPD) is a highly prevalent disease. Currently, severity Global initiative for chronic Obstructive Lung Disease (GOLD) criteria are used to diagnose the severity of COPD, but a new grading system, the body mass index, bronchial obstruction, dyspnea, exercise (BODE) index, was recently proposed to provide useful prognostic information. The objective of this study is to evaluate the association between health-related quality of life (HRQOL) and COPD severity assessed by two criteria: the GOLD classification and the BODE index. Sixty-four patients with COPD were examined with lung function tests and specific and generic HRQOL questionnaires (St. George’s Respiratory Questionnaire [SGRQ], Nottingham Health Profile [NHP]). Participants were divided into four severity groups using the GOLD guidelines and the BODE index quartiles. The association between NHP and SGRQ subscales, and the BODE index was significant ( P < 0.01). However, the GOLD classification shows a correlation only with SGRQ total score ( P < 0.05) but not with NHP or SGRQ subscales. There was an association of the SGRQ total score between the severity groups of BODE ( P = 0.0001), but there was no difference in the SGRQ total score between the severity groups of GOLD classification ( P = 0.244). The present study suggests that COPD severity assessed by the BODE index can be more directly related with HRQOL.
Cervical Spine Alignment During On-Field Management of Potential Catastrophic Spine Injuries
Authors: Swartz Erik E. , Rossi Gianluca Del 
Published: May 2009

Context: When cervical spine injuries are suspected, the cervical spine should be immobilized in a neutral position and neck motion controlled in preparation for transport to an emergency facility. Protocols for emergency transport utilizing common devices (cervical collars) and methods (transfer techniques) during these procedures are not entirely evidence based. Evidence Acquisition: The medical literature search covered the time period of January 1966 to June 2008 using the following keywords, either alone or in combination: extrication collars, cervical collars, spine orthoses, spinal immobilization, spine board, spinal board, transfer techniques, and back board. Biomedical databases searched included Medline, Web of Science, and Cumulative Index to Nursing and Allied Health Literature (CINAHL [1982 to 2008]). The reference lists of all trials identified were also searched for additional trials. Methods: Only trials that directly compared the efficacy or safety of transfer methods and/or immobilization devices were included. Studies that measured voluntary head movement after the fitting of the cervical orthoses and those that did not evaluate motion across individual spinal segments were not included. Results: A lift-and-slide transfer method with a full body immobilization device creates less motion than a log-roll maneuver. Extrication-type cervical immobilization collars are limited in their ability to control neck motion in the injured cadaveric model. Conclusion: Allied health professionals responsible for the management of the cervical spine–injured patient should become familiar with and employ a lift-and-slide transfer technique in appropriate situations and should not rely exclusively on extrication-type collars to immobilize the neck.
Low Back Pain in Young Athletes
Authors: Purcell Laura , Micheli Lyle 
Published: May 2009

Context: Low back pain in young athletes is a common complaint and should be taken seriously. It frequently results from a structural injury that requires a high degree of suspicion to diagnose and treat appropriately. Evidence Acquisition: A Medline search was conducted from 1996 to May 2008 using the search terms “low back pain in children” and “low back pain in athletes.” Known texts on injuries in young athletes were also reviewed. References in retrieved articles were additionally searched for relevant articles. Sources were included if they contained information regarding diagnosis and treatment of causes of low back pain in children. Results: Low back pain is associated with sports involving repetitive extension, flexion, and rotation, such as gymnastics, dance, and soccer. Both acute and overuse injuries occur, although overuse injuries are more common. Young athletes who present with low back pain have a high incidence of structural injuries such as spondylolysis and other injuries to the posterior elements of the spine. Disc-related pathology is much less common. Simple muscle strains are much less likely in this population and should be a diagnosis of exclusion only. Conclusion: Young athletes who present with low back pain are more likely to have structural injuries and therefore should be investigated fully. Muscle strain should be a diagnosis of exclusion. Treatment should address flexibility and muscle imbalances. Injuries can be prevented by recognizing and addressing risk factors. Return to sport should be a gradual process once the pain has resolved and the athlete has regained full strength.
Weight Management in Amateur Wrestling
Authors: Gibbs Aimee E. , Pickerman Joel , Sekiya Jon K. 
Published: May 2009

Context: Unhealthy weight loss practices continue to plague amateur wrestling. The National Collegiate Athletic Association weight loss guidelines are beneficial but have not solved the problem. Evidence Acquisition: All relevant databases through 2008 were searched using PubMed. The references of relevant articles were then searched for additional publications. Study Type: Clinical review. Results: New rules approved by the National Collegiate Athletic Association have been implemented in an attempt to prevent drastic weight loss practices in wrestlers. Although some are effective, such as establishing a minimum wrestling weight and decreasing the period between weigh-ins and actual wrestling, unsafe weight loss practices still occur. Conclusion: The attempts made by the National Collegiate Athletic Association to prevent drastic weight loss in wrestling have been effective to some degree. The mind-set of athletes, coaches, and clinicians needs to change if further improvements are to be made.
PAF-acetylhydrolase expressed during megakaryocyte differentiation inactivates PAF-like lipids
Authors: Foulks Jason M. , Marathe Gopal K. , Michetti Noemi , Stafforini Diana M. , Zimmerman Guy A. , McIntyre Thomas M. , Weyrich Andrew S. 
Published: April 2009

AbstractPlatelet activating factor (PAF) and PAF-like lipids induce inflammatory responses in target cells. These lipid mediators are inactivated by PAF-acetylhydrolase (PAF-AH). The PAF signaling system affects the growth of hematopoietic CD34+ cells, but roles for PAF-AH in this process are unknown. Here, we investigated PAF-AH function during megakaryopoiesis and found that human CD34+ cells accumulate this enzymatic activity as they differentiate toward megakaryocytes, consistent with the expression of mRNA and protein for the plasma PAF-AH isoform. Inhibition of endogenous PAF-AH activity in differentiated megakaryocytes increased formation of lipid mediators that signaled the PAF receptor (PAFR) in fully differentiated human cells such as neutrophils, as well as megakaryocytes themselves. PAF-AH also controlled megakaryocyte αIIbβ3-dependent adhesion, cell spreading, and mobility that relied on signaling through the PAFR. Together these data suggest that megakaryocytes generate PAF-AH to modulate the accumulation of intracellular phospholipid mediators that may detrimentally affect megakaryocyte development and function.
Vδ1 T lymphocytes producing IFN-γ and IL-17 are expanded in HIV-1–infected patients and respond to Candida albicans
Authors: Fenoglio Daniela , Poggi Alessandro , Catellani Silvia , Battaglia Florinda , Ferrera Alessandra , Setti Maurizio , Murdaca Giuseppe , Zocchi Maria Raffaella 
Published: April 2009

AbstractIn early HIV-1 infection, Vδ1 T lymphocytes are increased in peripheral blood and this is related to chemokine receptor expression, chemokine response, and recirculation. Herein we show that, at variance with healthy donors, in HIV-1–infected patients ex vivo–isolated Vδ1 T cells display cytoplasmic interferon-γ (IFN-γ). Interestingly, these cells coexpress cytoplasmic interleukin-17 (IL-17), and bear the CD27 surface marker of the memory T-cell subset. Vδ1 T cells, isolated from either patients or healthy donors, can proliferate and produce IFN-γ and IL-17 in response to Candida albicans in vitro, whereas Vδ2 T cells respond with proliferation and IFN-γ/IL-17 production to mycobacterial or phosphate antigens. These IFN-γ/IL-17 double-producer γδ T cells express the Th17 RORC and the Th1 TXB21 transcription factors and bear the CCR7 homing receptor and the CD161 molecule that are involved in γδ T-cell transendothelial migration. Moreover, Vδ1 T cells responding to C albicans express the chemokine receptors CCR4 and CCR6. This specifically equipped circulating memory γδ T-cell population might play an important role in the control of HIV-1 spreading and in the defense against opportunistic infections, possibly contributing to compensate for the impairment of CD4+ T cells.
NK cell–mediated killing of target cells triggers robust antigen-specific T cell–mediated and humoral responses
Authors: Krebs Philippe , Barnes Michael J. , Lampe Kristin , Whitley Karen , Bahjat Keith S. , Beutler Bruce , Janssen Edith , Hoebe Kasper 
Published: May 2009

AbstractPrevious work showed that administration of antigen-expressing apoptotic cells in vivo results in antigen-specific CD8+ T-cell responses independent of Toll-like receptor signaling. We report here that natural killer (NK) cells can serve a function directly upstream of this pathway and initiate robust adaptive immune responses via killing of antigen-expressing target cells. This pathway is highly sensitive, in that administration of as few as 104 target cells induced detectable antigen-specific CD8+ T-cell responses. Importantly, NK cell–mediated cytotoxicity of target cells could also induce robust antigen-specific CD4+ T-cell responses, which were critical for subsequent CD8+ T-cell priming and IgG responses. Unlike adaptive immune responses induced by gamma-irradiated cells, the NK-cell pathway required myeloid differentiating factor 88 (MyD88) and Toll/interleukin-1 receptor domain–containing adapter-inducinginterferon-β (Trif) signaling. NK cells have previously been shown to detect and kill pathogen-infected host cells, as well as neoplastic cells and tissue allografts. The present data provide further evidence that they also discharge a strong tie with their relatives in the adaptive immune system. We think that the recognition and killing of target cells by NK cells represents an important pathway for the generation of robust CD8+ T and humoral responses that may be exploited for vaccine development.
Discordance of MLL-rearranged (MLL-R) infant acute lymphoblastic leukemia in monozygotic twins with spontaneous clearance of preleukemic clone in unaffected twin
Authors: Chuk Meredith K. , McIntyre Emily , Small Donald , Brown Patrick 
Published: May 2009

Abstract
Concordance of MLL-rearranged acute leukemia in infant monozygotic twins is thought to be 100% with a very short latency period, suggesting that either the MLL fusion itself is sufficient to cause leukemia or that it promotes the rapid acquisition of additional oncogenic events that result in overt disease. We report the first case of discordance in an infant monozygotic twin pair. Twin A presented at age 9 months with MLL-ENL+ acute lymphoblastic leukemia and twin B remains healthy 3 years later. The presence and eventual clearance of a clonal population of MLL-ENL+ cells was shown in the bone marrow and peripheral blood of twin B. Clearance of this clone was temporally associated with viral-induced cytopenias, suggesting an immune-mediated clearance of the clone before the development of leukemia. Thus, concordance of MLL-rearranged acute leukemia in infant monozygotic twins is not universal. The implications of this case for MLL-rearranged leukemogenesis are discussed.
Involvement of TLR2 and TLR4 in inflammatory immune responses induced by fine and coarse ambient air particulate matter
Authors: Shoenfelt Joanna , Mitkus Robert J , Zeisler Rolf , Spatz Rabia O , Powell Jan , Fenton Matthew J , Squibb Katherine A , Medvedev Andrei E 
Published: May 2009

Abstract
Fine and coarse air pollution particles signal macrophage activation via differential utilization of Toll-like receptors (TLR) 2 and TLR4 but shared use of the MyD88 signaling pathway.
Induction of proinflammatory mediators by alveolar macrophages exposed to ambient air particulate matter has been suggested to be a key factor in the pathogenesis of inflammatory and allergic diseases in the lungs. However, receptors and mechanisms underlying these responses have not been fully elucidated. In this study, we examined whether TLR2, TLR4, and the key adaptor protein, MyD88, mediate the expression of proinflammatory cytokines and chemokines by mouse peritoneal macrophages exposed to fine and coarse PM. TLR2 deficiency blunted macrophage TNF-α and IL-6 expression in response to fine (PM2.5), while not affecting cytokine-inducing ability of coarse NIST Standard Reference Material (SRM 1648) particles. In contrast, TLR4−/− macrophages showed inhibited cytokine expression upon stimulation with NIST SRM 1648 but exhibited normal responses to PM2.5. Preincubation with polymyxin B markedly suppressed the capacity of NIST SRM 1648 to elicit TNF-α and IL-6, indicating endotoxin as a principal inducer of cytokine responses. Overexpression of TLR2 in TLR2/4-deficient human embryonic kidney 293 cells imparted PM2.5 sensitivity, as judged by IL-8 gene expression, whereas NIST SRM 1648, but not PM2.5 elicited IL-8 expression in 293/TLR4/MD-2 transfectants. Engagement of TLR4 by NIST SRM 1648 induced MyD88-independent expression of the chemokine RANTES, while TLR2-reactive NIST IRM PM2.5 failed to up-regulate this response. Consistent with the shared use of MyD88 by TLR2 and TLR4, cytokine responses of MyD88−/− macrophages to both types of air PM were significantly reduced. These data indicate differential utilization of TLR2 and TLR4 but shared use of MyD88 by fine and coarse air pollution particles.
Liver X receptor agonist regulation of Th17 lymphocyte function in autoimmunity
Authors: Xu Jihong , Wagoner Gail , Douglas James C , Drew Paul D 
Published: May 2009

Abstract
LXR agonists alter Th17 cell function and suppress EAE.
CD4+ Th17 cells are believed to play an important role in the development of a variety of autoimmune diseases including EAE, an animal model of MS. Previously, we and others demonstrated that LXR agonists suppressed the activation of primary glial cells and blocked the development of EAE. The present studies demonstrated that the LXR agonist T0901317 suppressed IL-17A expression from splenocytes derived from Vα2.3/Vβ8.2 TCR transgenic mice and from MOG35–55-immunized C57BL/6 mice. Furthermore, in vitro treatment with IL-23 alone or in combination with MOG35–55 induced IL-17A expression from splenocytes derived from MOG35–55-immunized mice, and T0901317 blocked this induction. In vitro treatment with the LXR agonist suppressed IL-23R expression by splenocytes. In addition, in vivo treatment with the LXR agonist suppressed IL-17A and IL-23R mRNA and protein expression in EAE mice. These studies suggest that LXR agonists suppress EAE, at least in part by suppressing IL-23 signaling. Recent studies indicate that the cytokines IL-21 and IL-22 are produced by Th17 cells and modulate immune responses. Our studies demonstrate that the LXR agonist T0901317 suppressed MOG35–55-induced expression of IL-21 and IL-22 mRNA in splenocytes derived from MOG35–55-immunized mice. Finally, we demonstrate that the LXR agonist T0901317 suppressed the development of EAE in an experimental paradigm involving treatment of established EAE. Collectively, these studies suggest that LXR agonists may be effective in the treatment of MS.
Functional implication of BAFF synthesis and release in gangliosides-stimulated microglia
Authors: Kim Kwang Soo , Park Ji-Young , Jou Ilo , Park Sang Myun 
Published: May 2009

Abstract
BAFF and BAFF receptors, which are expressed in microglia, may play an important role in CNS inflammation.
BAFF is a recently identified member of the TNF ligand superfamily that plays a critical role in B cell differentiation, survival, and regulation of Ig production. In the present study, we examined whether BAFF is expressed in microglia, and the expression and release of BAFF are regulated by gangliosides. The results showed that BAFF was expressed and released in rat primary microglia as well as in BV-2 cells. Furthermore, its expression and release were increased by gangliosides stimulation and regulated by JAK-STAT, especially the STAT1- and STAT3-dependent signaling pathways. It was of particular interest to observe that SP600125 and SB203580, specific inhibitors of JNK and p38, did not inhibit BAFF synthesis but inhibited the release of sBAFF in gangliosides-treated cells by regulating furin expression, suggesting that the JNK and p38 signaling pathways regulate the release but not the synthesis of BAFF. Moreover, BV-2 cells expressed BAFF-R on their cell surface, and rat primary microglia expressed BAFF-R and TACI on their cell surface. rBAFF increased the release of cytokines, especially IL-6, TNF-α, and IL-10, in rat primary microglia as well as in BV-2 cells. These findings imply that BAFF secreted by microglia may play important roles in CNS inflammation by regulating microglia as well as infiltrated B cells.
Inverse correlation between HPSE gene single nucleotide polymorphisms and heparanase expression: possibility of multiple levels of heparanase regulation
Authors: Ostrovsky Olga , Korostishevsky Michael , Shafat Itay , Mayorov Margarita , Ilan Neta , Vlodavsky Israel , Nagler Arnon 
Published: May 2009

Abstract
Combination of two HPSE gene single nucleotide polymorphisms predicts heparanase expression levels and possibly disease outcome.
Heparanase is an endo-β-glucuronidase that specifically cleaves the saccharide chains of heparan sulfate proteoglycans. Heparanase plays important roles in processes such as angiogenesis, tumor metastasis, tissue repair and remodeling, inflammation and autoimmunity. Genetic variations of the heparanase gene (HPSE) have been associated with heparanase transcription level. The present study was undertaken to identify haplotype or single nucleotide polymorphisms (SNPs) genotype combinations that correlate with heparanase expression both at the mRNA and protein levels. For this purpose, 11 HPSE gene SNPs were genotyped among 108 healthy individuals. Five out of the eleven polymorphisms revealed an association between the SNPs and heparanase expression. SNP rs4693608 exhibited a strong evidence of association. Analysis of haplotypes distribution revealed that the combination of two SNPs (rs4693608 and rs4364254) disclosed the most significant result. This approach allowed segregation of possible genotype combinations to three groups that correlate with low (LR: GG-CC, GG-CT, GG-TT, GA-CC), intermediate (MR: GA-CT, GA-TT) and high (HR: AA-TT, AA-CT) heparanase expression. Unexpectedly, LR genotype combinations were associated with low mRNA expressions level and high heparanase concentration in plasma, while HR genotype combinations were associated with high expression of mRNA and low plasma protein level. Because the main site of activity of secreted active heparanase is the extracellular matrix and cell surface, the origin and functional significance of plasma heparanase remain to be investigated. The current study indicates that rs4693608 and rs4364254 SNPs are involved in the regulation of heparanase expression and provides the basis for further studies on the association between HPSE gene SNPs and disease outcome.
Hemopexin down-regulates LPS-induced proinflammatory cytokines from macrophages
Authors: Liang Xueya , Lin Tian , Sun Guangjie , Beasley-Topliffe Laura , Cavaillon Jean-Marc , Warren H Shaw 
Published: April 2009

Abstract
The heme-binding protein hemopexin limits TLR4 and TLR2 agonist-induced macrophage cytokine production through a mechanism distinct from heme oxygenase-1.
Detection of LPS in tissues is an integral component of innate immunity that acts to protect against invasion by Gram-negative bacteria. Plasma down-regulates LPS-induced cytokine production from macrophages, thereby limiting systemic inflammation in blood and distant tissues. To identify the protein(s) involved in this process, we used classical biochemical chromatographic techniques to identify fractions of mouse sera that suppress LPS-induced TNF from bone marrow-derived macrophages (BMDMs). Fractionation yielded microgram quantities of a protein that was identified by MS to be hemopexin (Hx). Mouse Hx purified on hemin-agarose beads and rhHx decreased the production of cytokines from BMDMs and peritoneal macrophages induced by LPS. Preincubation of LPS with Hx did not affect the activity of LPS on LAL, whereas preincubation of Hx with macrophages followed by washing resulted in decreased activity of these cells in response to LPS, suggesting that Hx acts on macrophages rather than LPS. Heme-free Hx did not stimulate HO-1 in the macrophages. Purified Hx also decreased TNF and IL-6 from macrophages induced by the synthetic TLR2 agonist Pam3Cys. Our data suggest that Hx, which is an acute-phase protein that increases during inflammation, limits TLR4 and TLR2 agonist-induced macrophage cytokine production directly through a mechanism distinct from HO-1.
Immune-based therapy for chronic hepatitis C
Authors: Chang Dong-Yeop , Shin Eui-Cheol 
Published: April 2009

AbstractDevelopment of novel therapies for chronic hepatitis C by modulating innate and adaptive immune responses are reviewed.Chronic, persistent HCV infection is a public health issue. It often progresses to life-threatening complications, including liver cirrhosis and hepatocellular carcinoma. The current standard therapy is a combination of pegylated IFN-α and ribavirin. This therapy results in a sustained virologic response in only 50% of patients infected with HCV genotype 1 and is often accompanied with substantial side-effects. Therefore, it is imperative to develop novel therapies with higher efficacy and less substantial side-effects. Impaired immune responses to HCV are key features of chronic HCV infection; thus, intervention strategies typically involve boosting the immune responses against HCV. These immune-based therapies for chronic HCV infection include therapeutic vaccines, antagonists of T cell inhibitory factors, anti-HCV neutralizing antibodies, cytokines, and agonists for TLRs. Currently, various types of immune-based therapies are under development that might be used as a monotherapy or in combination with other antiviral drugs for the treatment of chronic HCV infection.