bluuebunny/crossref_metadata_2025_split huggingface dataset:
Epidemiology of severe cervical spinal trauma in the north area of São Paulo City: a 10-year prospective study
Authors: Santos Egmond Alves Silva , Filho Wenner Jorzino Santos , Possatti Lucas Loss , Bittencourt Lia Rita Azeredo , Fontoura Emílio Afonso França , Botelho Ricardo Vieira 
Published: July 2009

Object
The main objective was to study the epidemiological data obtained in patients with cervical spinal trauma (CST) in the north area of São Paulo City between 1997 and 2006.

Methods
All patients with severe CST in the north area of São Paulo City were studied. The data analyzed were age, sex, incidence, causes of trauma, level of trauma, morbidity, deaths, and complications. Analytical tests were performed to study risks of trauma and complications. The chi-square and analysis of variance tests were used for analytical data (significance level p < 0.05).

Results
The study population consisted of 217 patients who were hospitalized for CST. The average incidence rate was 21.6 cases annually or 1.8 cases monthly. The mean patient age was 36.75 years. The 20–40-year-old age bracket was found to be most highly represented, corresponding to 52.6% of total patients. Patients were predominantly male; 191 patients (88.01%) were male compared with only 26 female patients (11.99%). The ratio of men to women was 7.35:1. Injuries in the craniocervical region corresponded to 43 (19.8%) of the cases; injuries in the cervical subaxial region corresponded to 174 (80.2%) of the cases and were associated with worse neurological lesions. Additionally, 40.6% of patients presented with complications in other organs and systems; several patients presented with multiple complications, and 33 patients (15.02%) died. During the hospitalization period, 4 patients presenting as Grade A on the American Spinal Injury Association (ASIA) Scale evolved to Grade C, 1 patient presenting as ASIA Grade A evolved to Grade B, and 2 patients evolved to Grade E. Two patients who had been admitted without neurological lesions evolved to ASIA Grade C (1 patient postsurgery and 1 patient post-traction). Two patients presenting initially as ASIA Grade E evolved to Grade D, and another to central cord syndrome. On average, patients with incomplete lesions improved 1 grade in ASIA classification during hospitalization.

Conclusions
Data from severe CST observed in the current study suggest many differences in the characteristics described in the majority of published epidemiological studies and those found in patients in the north area of São Paulo City. It is likely that these differences reflect the urban and cultural habits and behaviors of the population specific to this area.
Decoding movement-related cortical potentials from electrocorticography
Authors: Reddy Chandan G. , Reddy Goutam G. , Kawasaki Hiroto , Oya Hiroyuki , Miller Lee E. , Howard Matthew A. 
Published: July 2009

Object
Control signals for brain-machine interfaces may be obtained from a variety of sources, each with their own relative merits. Electrocorticography (ECoG) provides better spatial and spectral resolution than scalp electroencephalography and does not include the risks attendant upon penetration of the brain parenchyma associated with single and multiunit recordings. For these reasons, subdural electrode recordings have been proposed as useful primary or adjunctive control signals for brain-machine interfaces. The goal of the present study was to determine if 2D control signals could be decoded from ECoG.

Methods
Six patients undergoing invasive monitoring for medically intractable epilepsy using subdural grid electrodes were asked to perform a motor task involving moving a joystick in 1 of 4 cardinal directions (up, down, left, or right) and a fifth condition (“trigger”). Evoked activity was synchronized to joystick movement and analyzed in the theta, alpha, beta, gamma, and high-gamma frequency bands.

Results
Movement-related cortical potentials could be accurately differentiated from rest with very high accuracy (83–96%). Further distinguishing the movement direction (up, down, left, or right) could also be resolved with high accuracy (58–86%) using information only from the high-gamma range, whereas distinguishing the trigger condition from the remaining directions provided better accuracy.

Conclusions
Two-dimensional control signals can be derived from ECoG. Local field potentials as measured by ECoG from subdural grids will be useful as control signals for a brain-machine interface.
Evidence for Genetic Association and Interaction Between the TYK2 and IRF5 Genes in Systemic Lupus Erythematosus
Authors: HELLQUIST ANNA , JÄRVINEN TIINA M. , KOSKENMIES SARI , ZUCCHELLI MARCO , ORSMARK-PIETRAS CHRISTINA , BERGLIND LINDA , PANELIUS JAANA , HASAN TAINA , JULKUNEN HEIKKI , D’AMATO MAURO , SAARIALHO-KERE ULPU , KERE JUHA 
Published: July 2009

Objective.Several candidate genes have been implicated in susceptibility for systemic lupus erythematosus (SLE), a complex autoimmune disease. The proposed genes include members of the type I interferon (IFN) pathway and genes involved in immunological defense functions. Our aim was to systematically replicate 6 such genes, TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2.Methods.Single-nucleotide polymorphisms in TYK2, IRF5, CTLA4, PDCD1, FCGR2A, and NOD2 were genotyped in 277 SLE patients and 356 healthy controls from Finland, giving a power of 42%–70% for different genes at published allele frequencies.Results.Significant association was seen for rs2304256 (p = 0.0001) and rs12720270 (p = 0.0031) in TYK2 and rs10954213 (p = 0.0043) in IRF5 in our samples, but not for the other genes. We found evidence for genetic interaction (p = 0.014) between rs2304256 in TYK2 and rs10954213 in IRF5, both members of the type I IFN pathway, strengthening the role of the type I IFN pathway in the pathogenesis of SLE.Conclusion.The IFN pathway genes IRF5 and TYK2 may act epistatically in increasing risk for SLE, but our lack of replication does not exclude effects of the other genes studied.
Mechanisms of Opioid-Mediated Inhibition of Human T Cell Receptor Signaling
Authors: Börner Christine , Warnick Beate , Smida Michal , Hartig Roland , Lindquist Jonathan A. , Schraven Burkhart , Höllt Volker , Kraus Jürgen 
Published: June 2009

AbstractOpioids are widely used for the treatment of severe pain. However, it is also known that opioids, in particular morphine, cause immunosuppression. Therefore, their use may complicate treatment of persons with an already impaired immune system, e.g., patients suffering from cancer or AIDS. We investigated the mechanisms of opioid-induced immunosuppression in primary human T lymphocytes and the human T cell line Jurkat. We demonstrated that morphine and the endogenous opioid β-endorphin inhibited the transcription of IL-2 in activated human T lymphocytes as well as the activation of the transcription factors AP-1, NFAT, and NF-κB, which transactivate IL-2. In addition, the TCR-induced calcium flux and MAPK activation were inhibited by the opioids, as well as proximal signaling events, such as the phosphorylation of the linker for activation of T cells and Zap70. A more detailed characterization of the mechanism revealed that incubation of T cells with the opioids caused a marked increase in cAMP. This in turn activated protein kinase A, which augmented the kinase activity of C-terminal Src kinase bound to phosphoprotein associated with glycosphingolipid-enrich microdomains, resulting in a further enhancement of the tonic inhibition of the leukocyte-specific protein tyrosine kinase Lck, thereby blocking the initiation of TCR signaling. These effects were mediated by μ opioid receptors. Our findings contribute to the understanding of immunosuppressive side effects of morphine. Since β-endorphin is expressed and secreted by immune effector cells, including T cells, and up-regulated in these cells by various stimuli, our data also suggest an inhibitory role for β-endorphin in the physiological regulation of T cell activation.
Focal Adhesion Kinase Regulates Pathogen-Killing Capability and Life Span of Neutrophils via Mediating Both Adhesion-Dependent and -Independent Cellular Signals
Authors: Kasorn Anongnard , Alcaide Pilar , Jia Yonghui , Subramanian Kulandayan K. , Sarraj Bara , Li Yitang , Loison Fabien , Hattori Hidenori , Silberstein Leslie E. , Luscinskas William F. , Luo Hongbo R. 
Published: June 2009

Abstract
Various neutrophil functions such as phagocytosis, superoxide production, and survival are regulated by integrin signaling. Despite the essential role of focal adhesion kinase (FAK) in mediating this signaling pathway, its exact function in neutrophils is ill defined. In this study, we investigated the role of FAK in neutrophils using a myeloid-specific conditional FAK knockout mouse. As reported in many other cell types, FAK is required for regulation of focal adhesion dynamics when neutrophils adhere to fibronectin or ICAM-1. Adhesion on VCAM-1-coated surfaces and chemotaxis after adhesion were not altered in FAK null neutrophils. In addition, we observed significant reduction in NADPH oxidase-mediated superoxide production and complement-mediated phagocytosis in FAK null neutrophils. As a result, these neutrophils displayed decreased pathogen killing capability both in vitro and in vivo in a mouse peritonitis model. In adherent cells, the defects associated with FAK deficiency are likely due to suppression of phosphatidylinositol (3,4,5)-trisphosphate (PtdIns(3,4,5)P3) signaling and chemoattractant-elicited calcium signaling. Disruption of FAK also reduced chemoattractant-elicited superoxide production in suspended neutrophils in the absence of cell adhesion. This may be solely caused by suppression of PtdIns(3,4,5)P3 signaling in these cells, because the fMLP-elicited calcium signal was not altered. Consistent with decreased PtdIns(3,4,5)P3/Akt signaling in FAK null neutrophils, we also observed accelerated spontaneous death in these cells. Taken together, our results revealed previously unrecognized roles of FAK in neutrophil function and provided a potential therapeutic target for treatment of a variety of infectious and inflammatory diseases.
The Opposite Effects of Acute and Chronic Alcohol on Lipopolysaccharide-Induced Inflammation Are Linked to IRAK-M in Human Monocytes
Authors: Mandrekar Pranoti , Bala Shashi , Catalano Donna , Kodys Karen , Szabo Gyongyi 
Published: June 2009

Abstract
Impaired host defense after alcohol use is linked to altered cytokine production, however, acute and chronic alcohol differently modulate monocyte/macrophage activation. We hypothesized that in human monocytes, acute alcohol induces hyporesponsiveness to LPS, resulting in decreased TNF-α, whereas chronic alcohol increases TNF-α by sensitization to LPS. We found that acute alcohol increased IL-1R-associated kinase-monocyte (IRAK-M), a negative regulator of IRAK-1, in human monocytes. This was associated with decreased IκBα kinase activity, NFκB DNA binding, and NFκB-driven reporter activity after LPS stimulation. In contrast, chronic alcohol decreased IRAK-M expression but increased IRAK-1 and IKK kinase activities, NFκB DNA binding, and NFκB-reporter activity. Inhibition of IRAK-M in acute alcohol-exposed monocytes using small interfering RNA restored the LPS-induced TNF-α production whereas over-expression of IRAK-M in chronic alcohol macrophages prevented the increase in TNF-α production. Addition of inhibitors of alcohol metabolism did not alter LPS signaling and TNF-α production during chronic alcohol exposure. IRAK-1 activation induces MAPKs that play an important role in TNF-α induction. We determined that acute alcohol decreased but chronic alcohol increased activation of ERK in monocytes and ERK inhibitor, PD98059, prevented the chronic alcohol-induced increase in TNF-α. In summary, inhibition of LPS-induced NFκB and ERK activation by acute alcohol leads to hyporesponsiveness of monocytes to LPS due to increased IRAK-M. In contrast, chronic alcohol sensitizes monocytes to LPS through decreased IRAK-M expression and activation of NFκB and ERK kinases. Our data indicate that IRAK-M is a central player in the opposite regulation of LPS signaling by different lengths of alcohol exposure in monocytes.
Autocrine IL-10 Induces Hallmarks of Alternative Activation in Macrophages and Suppresses Antituberculosis Effector Mechanisms without Compromising T Cell Immunity
Authors: Schreiber Tanja , Ehlers Stefan , Heitmann Lisa , Rausch Alexandra , Mages Jörg , Murray Peter J. , Lang Roland , Hölscher Christoph 
Published: June 2009

Abstract
Elevated IL-10 has been implicated in reactivation tuberculosis (TB). Since macrophages rather than T cells were reported to be the major source of IL-10 in TB, we analyzed the consequences of a macrophage-specific overexpression of IL-10 in transgenic mice (macIL-10-transgenic) after aerosol infection with Mycobacterium tuberculosis (Mtb). MacIL-10 transgenic mice were more susceptible to chronic Mtb infection than nontransgenic littermates, exhibiting higher bacterial loads in the lung after 12 wk of infection and dying significantly earlier than controls. The differentiation, recruitment, and activation of Th1 cells as well as the induction of IFN-γ-dependent effector genes against Mtb were not affected by macrophage-derived IL-10. However, microarray analysis of pulmonary gene expression revealed patterns characteristic of alternative macrophage activation that were overrepresented in Mtb-infected macIL-10 transgenic mice. Importantly, arginase-1 gene expression and activity were strikingly enhanced in transgenic mice accompanied by a reduced production of reactive nitrogen intermediates. Moreover, IL-10-dependent arginase-1 induction diminished antimycobacterial effector mechanisms in macrophages. Taken together, macrophage-derived IL-10 triggers aspects of alternative macrophage activation and promotes Mtb recrudescence independent of overt effects on anti-TB T cell immunity.
Lethal Effect of CD3-Specific Antibody in Mice Deficient in TGF-β1 by Uncontrolled Flu-Like Syndrome
Authors: Perruche Sylvain , Zhang Pin , Maruyama Takashi , Bluestone Jeffrey A. , Saas Philippe , Chen WanJun 
Published: June 2009

Abstract
CD3-specific Ab therapy results in a transient, self-limiting, cytokine-associated, flu-like syndrome in experimental animals and in patients, but the underlying mechanism for this spontaneous resolution remains elusive. By using an in vivo model of CD3-specific Ab-induced flu-like syndrome, we show in this paper that a single injection of sublethal dose of the Ab killed all TGF-β1−/− mice. The death of TGF-β1−/− mice was associated with occurrence of this uncontrolled flu-like syndrome, as demonstrated by a sustained storm of systemic inflammatory TNF and IFN-γ cytokines. We present evidence that deficiency of professional phagocytes to produce TGF-β1 after apoptotic T cell clearance may be responsible, together with hypersensitivity of T cells to both activation and apoptosis, for the uncontrolled inflammation. These findings indicate a key role for TGF-β1 and phagocytes in protecting the recipients from lethal inflammation and resolving the flu-like syndrome after CD3-specific Ab treatment. The study may also provide a novel molecular mechanism explaining the early death in TGF-β1−/− mice.
Heat Shock Protein 60, via MyD88 Innate Signaling, Protects B Cells from Apoptosis, Spontaneous and Induced
Authors: Cohen-Sfady Michal , Pevsner-Fischer Meirav , Margalit Raanan , Cohen Irun R. 
Published: June 2009

Abstract
We recently reported that heat shock protein 60 (HSP60) via TLR4 signaling activates B cells and induces them to proliferate and secrete IL-10. We now report that HSP60 inhibits mouse B cell apoptosis, spontaneous or induced by dexamethasone or anti-IgM activation. Unlike HSP60 enhancement of B cell proliferation and IL-10 secretion, TLR4 signaling was not required for the inhibition of apoptosis by HSP60; nevertheless, MyD88 was essential. Inhibition of apoptosis by HSP60 was associated with up-regulation of the antiapoptotic molecules Bcl-2, Bcl-xL, and survivin, maintenance of the mitochondrial transmembrane potential, and inhibition of caspase-3 activation. Moreover, B cells incubated with HSP60 manifested prolonged survival following transfer into recipient mice. These results extend the varied role of HSP60 in the innate regulation of the adaptive immune response.
Activation of the Akt-NF-κB Pathway by Subtilase Cytotoxin through the ATF6 Branch of the Unfolded Protein Response
Authors: Yamazaki Hiroaki , Hiramatsu Nobuhiko , Hayakawa Kunihiro , Tagawa Yasuhiro , Okamura Maro , Ogata Ryouji , Huang Tao , Nakajima Shotaro , Yao Jian , Paton Adrienne W. , Paton James C. , Kitamura Masanori 
Published: June 2009

Abstract
Shiga toxin has the potential to induce expression of inflammation-associated genes, although the underlying mechanisms are not well understood. We examined the effects of subtilase cytotoxin (SubAB), an AB5 toxin produced by some Shiga toxigenic Escherichia coli, on the activation of NF-κB. SubAB is known to be a protease which selectively degrades GRP78/Bip. Treatment of NRK-52E cells with SubAB caused rapid cleavage of GRP78. Following the degradation of GRP78, transient activation of NF-κB was observed with a peak at 6–12 h; the activation subsided within 24 h despite the continuous absence of intact GRP78. The activation of NF-κB was preceded by transient phosphorylation of Akt. Treatment of the cells with a selective inhibitor of Akt1/2 or an inhibitor of PI3K attenuated SubAB-induced NF-κB activation, suggesting that activation of Akt is an event upstream of NF-κB. Degradation of GRP78 caused the unfolded protein response (UPR), and inducers of the UPR mimicked the stimulatory effects of SubAB on Akt and NF-κB. SubAB triggered the three major branches of the UPR including the IRE1-XBP1, PERK, and ATF6 pathways. Dominant-negative inhibition of IRE1α, XBP1, or PERK did not attenuate activation of NF-κB by SubAB. In contrast, genetic and pharmacological inhibition of ATF6 significantly suppressed SubAB-triggered Akt phosphorylation and NF-κB activation. These results suggested that loss of GRP78 by SubAB leads to transient phosphorylation of Akt and consequent activation of NF-κB through the ATF6 branch of the UPR.
Patent Filarial Infection Modulates Malaria-Specific Type 1 Cytokine Responses in an IL-10-Dependent Manner in a Filaria/Malaria-Coinfected Population
Authors: Metenou Simon , Dembélé Benoit , Konate Siaka , Dolo Housseini , Coulibaly Siaka Y. , Coulibaly Yaya I. , Diallo Abdallah A. , Soumaoro Lamine , Coulibaly Michel E. , Sanogo Dramane , Doumbia Salif S. , Wagner Marissa , Traoré Sekou F. , Klion Amy , Mahanty Siddhartha , Nutman Thomas B. 
Published: June 2009

Abstract
The effect of filarial infections on malaria-specific immune responses was investigated in Malian villages coendemic for filariasis (Fil) and malaria. Cytokines were measured from plasma and Ag-stimulated whole blood from individuals with Wuchereria bancrofti and/or Mansonella perstans infections (Fil+; n = 19) and those without evidence of filarial infection (Fil−; n = 19). Plasma levels of IL-10 (geometric mean [GM], 22.8 vs 10.4) were higher in Fil+ compared with Fil−, whereas levels of IFN-inducible protein (IP)-10 were lower in Fil+ (GM, 66.3 vs 110.0). Fil+ had higher levels of spontaneously secreted IL-10 (GM, 59.3 vs 6.8 pg/ml) and lower levels of IL-2 (1.0 vs 1.2 pg/ml) than did Fil−. Although there were no differences in levels of Staphylococcus aureus enterotoxin B-induced cytokines between the two groups, Fil+ mounted lower IL-12p70 (GM, 1.11 vs 3.83 pg/ml; p = 0.007), IFN-γ (GM, 5.44 vs 23.41 pg/ml; p = 0.009), and IP-10 (GM, 29.43 vs 281.7 pg/ml; p = 0.007) responses following malaria Ag (MalAg) stimulation compared with Fil−. In contrast, Fil+ individuals had a higher MalAg-specific IL-10 response (GM, 7318 pg/ml vs 3029 pg/ml; p = 0.006) compared with those without filarial infection. Neutralizing Ab to IL-10 (but not to TGFβ) reversed the down-regulated MalAg-specific IFN-γ and IP-10 (p &lt; 0.001) responses in Fil+. Together, these data demonstrate that filarial infections modulate the Plasmodium falciparum-specific IL-12p70/IFN-γ secretion pathways known to play a key role in resistance to malaria and that they do so in an IL-10-dependent manner.
T Cell Responses in the Absence of IFN-γ Exacerbate Uterine Infection with Chlamydia trachomatis
Authors: Gondek David C. , Roan Nadia R. , Starnbach Michael N. 
Published: June 2009

Abstract
Infection with the obligate intracellular bacterium Chlamydia trachomatis is controlled primarily by IFN-γ and Th1 immunity. In this study, we used cells from a Chlamydia-specific CD4+ TCR-transgenic mouse to assess the role of IFN-γ in development of Th1 immunity. We show that secretion of host IFN-γ or the ability of host cells to respond to secreted IFN-γ is not required to initiate a Th1 immune response. Additionally, we found that Ag-specific CD4+ cells that were preskewed toward Th1 confer protection, whereas cells preskewed toward Th2 cause a previously unreported exacerbation of disease leading to higher bacterial load. Chlamydia-specific Th1 cells transferred into an IFN-γ−/− recipient mouse demonstrate protective effects, but the same cells exacerbate bacterial burden when transferred into IFN-γR−/− mice. Thus, we demonstrate that the secretion of IFN-γ is necessary for protection against C. trachomatis and that in the absence of host cell IFN-γR expression, both Th1 and Th2 cells lead to increased burden of C. trachomatis.
Role of MAPK Kinase 6 in Arthritis: Distinct Mechanism of Action in Inflammation and Cytokine Expression
Authors: Yoshizawa Toshio , Hammaker Deepa , Boyle David L. , Corr Maripat , Flavell Richard , Davis Roger , Schett Georg , Firestein Gary S. 
Published: June 2009

Abstract
Development of p38α inhibitors for rheumatoid arthritis has been hindered by toxicity and limited efficacy. Therefore, we evaluated whether MKK6, an upstream kinase that regulates multiple p38 isoforms, might be an alternative therapeutic target in inflammatory arthritis. Wild-type (WT), MKK6−/−, and MKK3−/− mice were administered K/B×N serum to induce arthritis. Articular expression of activated kinases and cytokines was determined by Western blot, qPCR, ELISA, and multiplex analysis. Immunoprecipitation and confocal microscopy experiments were performed to determine the subcellular location of MKK6, P-p38, and MAPKAPK2 (MK2). Arthritis scores were significantly lower in MKK6−/− mice compared with WT mice. Joint destruction and osteoclast differentiation were lower in MKK6−/−, as were articular IL-6 and matrix metalloproteinase-3 expression. Phospho-p38 levels were modestly decreased in the joints of arthritic MKK6−/− mice compared with WT but were significantly higher than MKK3−/− mice. P-MK2 was low in MKK6−/− and MKK3−/− mice. Uncoupled p38 and MK2 activation was also observed in cultured, MKK6−/− FLS and confirmed using kinase assays. Immunoprecipitation assays and confocal microscopy showed that P-p38 and MK2 colocalized in activated WT but not MKK6−/− FLS. Distinct patterns of cytokine production were observed in MKK6−/− and MKK3−/− cells. MKK6 deficiency suppresses inflammatory arthritis and joint destruction, suggesting it might be a therapeutic target for inflammation. Although MKK3 and MKK6 activate the p38 pathway, they regulate distinct subsets of proinflammatory cytokines. MKK6 appears mainly to facilitate p38 and MK2 colocalization in the nucleus rather than to phosphorylate p38.