bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-8 Secretion of Cortical Tubular Epithelial Cells Is Directed to the Basolateral Environment and Is Not Enhanced by Apical Exposure toEscherichia coli
Authors: Krüger Sabine , Brandt Ernst , Klinger Matthias , Krüger Stefan , Kreft Burkhard 
Published: May 2009

ABSTRACTIn upper urinary tract infections, tubular epithelial cells (TEC) may play a pivotal role in the initiation of the renal inflammatory response. They exert crucial immunological functions such as processing and presentation of foreign antigen, secretion of proinflammatory cytokines (interleukin-6 [IL-6] and tumor necrosis factor alpha) and chemokines (IL-8, MCP-1, ENA-78, and RANTES). Since monolayer cultures are a limited model for polarized tubular epithelial cells, we studied the side-dependent IL-8 secretion of TEC by using cell culture inserts as a basement membrane imitation. Primary cultures of proximal TEC were stimulated with differently fimbriated mutants ofEscherichia coli,E. coliLPS, S-fimbria isolates, and IL-1α. IL-8 protein was measured by enzyme-linked immunosorbent assay, and IL-8-like biological activity was tested by measuring elastase release from polymorphonuclear cells in supernatants of the upper and lower compartments. IL-8 mRNA was compared by competitive PCR. IL-8 secretion by TEC into the basolateral environment was significantly higher than secretion into the apical compartment, representing the tubular lumen. However, stimulation of IL-8 secretion by TEC was restricted to IL-1α and was not inducible byE. colimutants, S fimbriae, or lipopolysaccharide. With this in vitro model of polarized TEC, we show that luminal contact of TEC with uropathogenicE. colidoes not result in enhanced IL-8 secretion. The basolaterally directed production of the neutrophil chemotactic factor IL-8 by TEC after stimulation with IL-1α might play an important role in the initiation of inflammatory cell influx into the renal parenchyma.
A P5 Peptide That Is Homologous to Peptide 10 of OprF from
Pseudomonas aeruginosa
Enhances Clearance of Nontypeable
Haemophilus influenzae
from Acutely Infected Rat Lung in the Absence of Detectable Peptide-Specific Antibody
Authors: Webb Dianne C. , Cripps Allan W. 
Published: May 2009

ABSTRACT

Nontypeable
Haemophilus influenzae
(NTHi) is an opportunistic pathogen associated with otitis media and the exacerbation of chronic bronchitis. This study reports the vaccine potential of three peptides representing conserved regions of the NTHi P5 outer membrane protein which have been fused to a promiscuous measles virus F protein T-cell eptitope (MVF). The peptides correspond to a region in surface loop one (MVF/L1A), the central region of loop four (MVF/L4), and a C-terminal region homologous to peptide 10 of OprF from
Pseudomonas aeruginosa
(MVF/H3). Immunization of rats with MVF/H3 was the most efficacious in significantly reducing the number of viable NTHi in both the broncho-alveolar lavage fluid (74%) and lung homogenates (70%), compared to control rats. Importantly, despite significantly increased rates of clearance, immunization with MVF/H3 elicited poor antibody responses, suggesting that cell-mediated rather than humoral responses play an important role in the enhanced clearance of NTHi in this model.
DNA Vaccination with Genes EncodingToxoplasma gondiiAntigens GRA1, GRA7, and ROP2 Induces Partially Protective Immunity against Lethal Challenge in Mice
Authors: Vercammen M. , Scorza T. , Huygen K. , De Braekeleer J. , Diet R. , Jacobs D. , Saman E. , Verschueren H. 
Published: May 2009

ABSTRACTC57BL/6, C3H, and BALB/c mice were vaccinated with plasmids encodingToxoplasma gondiiantigens GRA1, GRA7, and ROP2, previously described as strong inducers of immunity. Seroconversion for the relevant antigen was obtained in the majority of the animals.T. gondiilysate stimulated specific T-cell proliferation and secretion of gamma interferon (IFN-γ) in spleen cell cultures from vaccinated BALB/c and C3H mice but not in those from control mice. Although not proliferating, stimulated splenocytes from DNA-vaccinated C57BL/6 mice also produced IFN-γ. No interleukin-4 was detected in the supernatants of lysate-stimulated splenocytes from DNA-vaccinated mice in any of the mouse strains evaluated. As in infected animals, a high ratio of specific immunoglobulin G2a (IgG2a) to IgG1 antibodies was found in DNA-vaccinated C3H mice, suggesting that a Th1-type response had been induced. For BALB/c mice, the isotype ratio of the antibody response to DNA vaccination was less polarized. The protective potential of DNA vaccination was demonstrated in C3H mice. C3H mice vaccinated with plasmid encoding GRA1, GRA7, or ROP2 were partially protected against a lethal oral challenge with cysts of two differentT. gondiistrains: survival rates increased from 10% in controls to at least 70% after vaccination in one case and from 50% to at least 90% in the other. In vaccinated C3H mice challenged with a nonlethalT. gondiidose, the number of brain cysts was significantly lower than in controls. DNA vaccination did not protect BALB/c or C57BL/6 mice. Our results demonstrate for the first time in an animal model a partially protective effect of DNA vaccination againstT. gondii.
Evaluation of
Mycobacterium tuberculosis
Genes Involved in Resistance to Killing by Human Macrophages
Authors: Miller Barbara H. , Shinnick Thomas M. 
Published: May 2009

ABSTRACT

A coinfection assay was developed to examine
Mycobacterium tuberculosis
genes suspected to be involved in resistance to killing by human macrophages. THP-1 macrophages were infected with a mixture of equal numbers of recombinant
Mycobacterium smegmatis
LR222 bacteria expressing an
M. tuberculosis
gene and wild-type
M. smegmatis
LR222 bacteria expressing the
xylE
gene. At various times after infection, the infected macrophages were lysed and the bacteria were plated. The resulting colonies were sprayed with catechol to determine the number of recombinant colonies and the number of
xylE
-expressing colonies.
M. smegmatis
bacteria expressing the
M. tuberculosis
glutamine synthetase A (
glnA
) gene or open reading frame
Rv2962c
or
Rv2958c
demonstrated significantly increased survival rates in THP-1 macrophages relative to those of
xylE
-expressing bacteria.
M. smegmatis
bacteria expressing
M. tuberculosis
genes for phospholipase C (
plcA
and
plcB
) or for high temperature requirement A (
htrA
) did not.
Inhibition of
Borrelia burgdorferi
Migration from the Midgut to the Salivary Glands following Feeding by Ticks on OspC-Immunized Mice
Authors: Gilmore Robert D. , Piesman Joseph 
Published: May 2009

ABSTRACT

Borrelia burgdorferi
-infected ticks were fed on either OspC-immunized mice or normal, nonimmunized mice. After 72 h, the ticks were detached, followed by dissection and subsequent culturing in Barbour-Stoenner-Kelley II medium of the salivary glands from each tick to determine the presence of borreliae. Forty percent (10 of 25) of salivary glands from ticks that had fed on nonimmunized mice were culture positive, while only 7.4% (2 of 27) of salivary glands from ticks that had fed on OspC-immunized mice were culture positive, thus indicating a much reduced borrelial migration from the midgut when the bloodmeal contained anti-OspC antibodies. Fluorescent antibody staining of the corresponding midguts from ticks that had fed on the OspC-immunized mice showed that borreliae were present but did not produce OspC. In contrast, borreliae in midguts from ticks that had fed on normal mice demonstrated substantial
ospC
expression. This study provides evidence that, during tick feeding on an OspC-immunized host, transmission of borreliae from the tick is prevented; it also suggests that OspC functions in a tick-to-host transmission mechanism.
Lymphocyte Function-Associated Antigen 1 Is a Receptor forPasteurella haemolyticaLeukotoxin in Bovine Leukocytes
Authors: Jeyaseelan S. , Hsuan S. L. , Kannan M. S. , Walcheck B. , Wang J. F. , Kehrli M. E. , Lally E. T. , Sieck G. C. , Maheswaran S. K. 
Published: May 2009

ABSTRACTPasteurella (Mannheimia) haemolyticaleukotoxin (Lkt) causes cell type- and species-specific effects in ruminant leukocytes. Recent studies indicate thatP. haemolyticaLkt binds to bovine CD18, the common subunit of all β2 integrins. We designed experiments with the following objectives: to identify which member of the β2 integrins is a receptor for Lkt; to determine whether Lkt binding to the receptor is target cell (bovine leukocytes) specific; to define the relationships between Lkt binding to the receptor, calcium elevation, and cytolysis; and to determine whether a correlation exists between Lkt receptor expression and the magnitude of target cell cytolysis. We compared Lkt-induced cytolysis in neutrophils from control calves and from calves with bovine leukocyte adhesion deficiency (BLAD), because neutrophils from BLAD-homozygous calves exhibit reduced β2 integrin expression. The results demonstrate for the first time that Lkt binds to bovine CD11a and CD18 (lymphocyte function-associated antigen 1 [LFA-1]). The binding was abolished by anti-CD11a or anti-CD18 monoclonal antibody (MAb). Lkt-induced calcium elevation in bovine alveolar macrophages (BAMs) was inhibited by anti-CD11a or anti-CD18 MAb (65 to 94% and 37 to 98%, respectively, at 5 and 50 Lkt units per ml;P< 0.05). Lkt-induced cytolysis in neutrophils and BAMs was also inhibited by anti-CD11a or anti-CD18 MAb in a concentration-dependent manner. Lkt bound to porcine LFA-1 but did not induce calcium elevation or cytolysis. In neutrophils from BLAD calves, Lkt-induced cytolysis was decreased by 44% compared to that of neutrophils from control calves (P< 0.05). These results indicate that LFA-1 is a Lkt receptor, Lkt binding to LFA-1 is not target cell specific, Lkt binding to bovine LFA-1 correlates with calcium elevation and cytolysis, and bovine LFA-1 expression correlates with the magnitude of Lkt-induced target cell cytolysis.
8-Isocyanoamphilecta-11(20),15-diene, a new antimalarial isonitrile diterpene from the sponge Ciocalapata sp.
Authors: Wattanapiromsakul Chatchai , Chanthathamrongsiri Naphatson , Bussarawit Somchai , Yuenyongsawad Supreeya , Plubrukarn Anuchit , Suwanborirux Khanit 
Published: May 2009

A new isonitrile diterpene of the amphilectane family, 8-isocyanoamphilecta-11(20),15-diene (4), was isolated from the sponge Ciocalapata sp., along with three known isonitriles, 8,15-diisocyano-11(20)-amphilectene (1), 7-isocyanoamphilecta-11(20),15-diene (2), and 8-isocyanoamphilecta-11(20),14-diene (3), and two steroidal peroxides, ergosterol peroxide (5) and 5α,9α-epidioxy-8α,14α-epoxy-(22E)-ergosta-6,22-dien-3β-ol (6). The structure of the new isonitrile was elucidated spectroscopically. In addition, anomalous multiplicities in the NMR spectra of some isolated isonitriles were observed and are reported here. The four isonitriles were strongly active against Plasmodium falciparum K1 with IC50 in a range of 0.09–1.07 μmol/L. Except for 1, which was cytotoxic against both MCF-7 and fibroblast cell lines, the other three diterpenes showed no significant cytotoxicity against either targeted cell lines. On the other hand, the steroidal peroxides 5 and 6, which were less active in the antimalarial bioassay (IC50 values of 6.28 and 7.13 µmol/L, respectively), were strongly cytotoxic against MCF-7 (IC50 values of 0.025 and 0.003 µmol/L, respectively), with very little toxicity against human fibroblasts.
Peri-epiphyseal and Overuse Injuries in Adolescent Athletes
Authors: Frush Todd J. , Lindenfeld Thomas N. 
Published: May 2009

Context: Overuse injuries of the musculoskeletal system in immature athletes are commonly seen in medical practice. Evidence Acquisition: An analysis of published clinical, outcome, and biomechanical studies of adolescent epiphyseal and overuse injuries was performed through 2008 to increase recognition and provide treatment recommendations. Results: Adolescent athletes can sustain physeal and bony stress injuries. Recovery and return to play occur more swiftly if such injuries are diagnosed early and immobilized until the patient is pain-free, typically about 4 weeks for apophyseal and epiphyseal overuse injuries. Certain epiphyseal injuries have prolonged symptoms with delayed treatment, including those involving the bones in the hand, elbow, and foot. If such injuries are missed, prolonged healing and significant restrictions in athletic pursuits may occur. Conclusion: Some of these injuries are common to all weightbearing sports and are therefore widely recognized. Several are common in gymnastics but are rarely seen in other athletes. Early recognition and treatment of these conditions lead to quicker recovery and so may prevent season-ending, even career-ending, events from occurring.
Strength Training in Children and Adolescents: Raising the Bar for Young Athletes?
Authors: Dahab Katherine Stabenow , McCambridge Teri Metcalf 
Published: May 2009

Context: Strength training in children, in combination with plyometric and/or agility training, has become an increasingly popular tactic for athletes to gain a competitive edge during the off-season. The present review clarifies some common myths associated with strength training in children, and it outlines the most current recommendations. Evidence Acquisition: Relevant studies on strength training in children and adolescents were reviewed (search results included studies indexed in PubMed and MEDLINE from 1980 through 2008). Also reviewed were recommendations from consensus guidelines and position statements applicable to strength training in youth. Results: Children can improve strength by 30% to 50% after just 8 to 12 weeks of a well-designed strength training program. Youth need to continue to train at least 2 times per week to maintain strength. The case reports of injuries related to strength training, including epiphyseal plate fractures and lower back injuries, are primarily attributed to the misuse of equipment, inappropriate weight, improper technique, or lack of qualified adult supervision. Conclusion: Youth—athletes and nonathletes alike—can successfully and safely improve their strength and overall health by participating in a well-supervised program. Trained fitness professionals play an essential role in ensuring proper technique, form, progression of exercises, and safety in this age group.
Risk Factors for Medical Withdrawals in United States Tennis Association Junior National Tennis Tournaments: A Descriptive Epidemiologic Study
Authors: Jayanthi Neeru A. , O’Boyle Jeff , Durazo-Arvizu Ramon A. 
Published: May 2009

Background: There have been no large-scale epidemiologic studies designed to determine the risk factors related to medical withdrawal in United States Tennis Association junior national tennis tournaments. Hypothesis: Risk of medical withdrawal will increase on the basis of cumulative match volume within a tournament. Methods: A retrospective, cross-sectional analysis was performed of data collected for every match of all 4 United States Tennis Association supernational tournaments (spring, summer, fall, winter) for the boys and girls divisions and for all age divisions (12, 14, 16, 18) during a single year (2005). Logistic regression analysis was performed to determine relative risk of all risk factors. Additional analysis was performed to determine the threshold (ie, match number) at which a player would substantially increase his or her risk of medical withdrawal. Results: A total of 28 336 match exposures were analyzed, with an even distribution with respect to sex and age. The total medical withdrawal rate was 15.6 per 1000 match exposures. Every factor of interest was highly significant in predicting a higher rate of medical withdrawal per 1000 match exposures. The medical withdrawal rate was significantly higher in the fifth match or greater (26.3/1000) versus the first 4 matches (12.7/1000; P < .0001), even when analyzing main draw and singles matches. Conclusion: In United States Tennis Association national junior tennis tournaments, there is a significant increase in risk of medical withdrawals directly related to older age divisions, boys, singles matches, and main draw matches. Specifically, there is a significant increase in medical withdrawal rate beyond the fourth match in the tournament regardless of whether it is a main draw, consolation, or singles match. Clinical Relevance: Recommendations can be made to exercise caution in tournaments that involve boys, older age divisions, and singles. In addition, there may be sufficient evidence to suggest intervention within a tournament when players play beyond their fourth match.
TGF-β induces degradation of TAL1/SCL by the ubiquitin-proteasome pathway through AKT-mediated phosphorylation
Authors: Terme Jean-Michel , Lhermitte Ludovic , Asnafi Vahid , Jalinot Pierre 
Published: May 2009

Abstract
T-cell acute lymphoblastic leukemia 1 (TAL1), also known as stem cell leukemia (SCL), plays important roles in differentiation of hematopoietic and endothelial cells and is deregulated in a high percentage of T-cell acute lymphoblastic leukemia (T-ALL). In this report we show that the intracellular concentration of TAL1 is regulated by transforming growth factor β (TGF-β), which triggers its polyubiquitylation and degradation by the proteasome. This effect is mediated by AKT1, which phosphorylates TAL1 at threonine 90. Immunoprecipitation experiments showed that this event increases association of TAL1 with the E3 ubiquitin ligase CHIP. The E47 heterodimerization partner of TAL1 hinders this association. Our observations indicate that activation of the TGF-β and phosphatidylinositol 3-kinase/AKT pathways might reverse overexpression of TAL1 in leukemic cells by inducing proteolysis of this important oncogene.
High-resolution genomic profiling of childhood T-ALL reveals frequent copy-number alterations affecting the TGF-β and PI3K-AKT pathways and deletions at 6q15-16.1 as a genomic marker for unfavorable early treatment response
Authors: Remke Marc , Pfister Stefan , Kox Corinne , Toedt Grischa , Becker Natalia , Benner Axel , Werft Wiebke , Breit Stephen , Liu Shuangyou , Engel Felix , Wittmann Andrea , Zimmermann Martin , Stanulla Martin , Schrappe Martin , Ludwig Wolf-Dieter , Bartram Claus R. , Radlwimmer Bernhard , Muckenthaler Martina U. , Lichter Peter , Kulozik Andreas E. 
Published: May 2009

Abstract
Precursor T-cell acute lymphoblastic leukemia (T-ALL) in children represents a clinical challenge, because relapses are usually fatal. It is thus necessary to identify high-risk patients as early as possible to effectively individualize treatment. We aimed to define novel molecular risk markers in T-ALL and performed array-based comparative genomic hybridization (array-CGH) and expression analyses in 73 patients. We show that DNA copy-number changes are common in T-ALL and affect 70 of 73 (96%) patients. Notably, genomic imbalances predicted to down-regulate the TGF-β or up-regulate the PI3K-AKT pathways are identified in 25 of 73 (34%) and 21 of 73 (29%) patients, suggesting that these pathways play key roles in T-ALL leukemogenesis. Furthermore, we identified a deletion at 6q15-16.1 in 9 of 73 (12%) of the patients, which predicts poor early treatment response. This deletion includes the CASP8AP2 gene, whose expression is shown to be down-regulated. The interaction of CASP8AP2 with CASP8 plays a crucial role in apoptotic regulation, suggesting a functional link between the clinical effect of the deletion and the molecular mode of action. The data presented here implicate the TGF-β and PI3K-AKT pathways in T-ALL leukemogenesis and identify a subgroup of patients with CASP8AP2 deletions and poor early treatment response.
GM-CSF- and M-CSF-dependent macrophage phenotypes display differential dependence on Type I interferon signaling
Authors: Fleetwood Andrew J , Dinh Hang , Cook Andrew D , Hertzog Paul J , Hamilton John A 
Published: May 2009

Abstract
Type I IFN differentially regulates the phenotype, function and polarization of particular macrophage populations.
M-CSF and GM-CSF are mediators involved in regulating the numbers and function of macrophage lineage populations and have been shown to contribute to macrophage heterogeneity. Type I IFN is an important mediator produced by macrophages and can have profound regulatory effects on their properties. In this study, we compared bone marrow-derived macrophages (BMM) and GM-CSF-induced BMM (GM-BMM) from wild-type and IFNAR1−/− mice to assess the contribution of endogenous type I IFN to the phenotypic differences between BMM and GM-BMM. BMM were capable of higher constitutive IFN-β production, which contributed significantly to their basal transcriptome. Microarray analysis found that of the endogenous type I IFN-regulated genes specific to either BMM or GM-BMM, 488 of these gene alterations were unique to BMM, while only 50 were unique to GM-BMM. Moreover, BMM displayed enhanced basal mRNA levels, relative to GM-BMM, of a number of genes identified as being dependent on type I IFN signaling, including Stat1, Stat2, Irf7, Ccl5, Ccl12, and Cxcl10. As a result of prior type I IFN “priming,” upon LPS stimulation BMM displayed increased activation of the MyD88-independent IRF-3/STAT1 pathways compared with GM-BMM, which correlated with the distinct cytokine/chemokine profiles of the two macrophage subsets. Furthermore, the autocrine type I IFN signaling loop regulated the production of the M1 and M2 signature cytokines, IL-12p70 and IL-10. Collectively, these findings demonstrate that constitutive and LPS-induced type I IFN play significant roles in regulating the differences in phenotype and function between BMM and GM-BMM.
Thymocyte-Synthesized Glucocorticoids Play a Role in Thymocyte Homeostasis and Are Down-Regulated by Adrenocorticotropic Hormone
Authors: Qiao Shengjun , Okret Sam , Jondal Mikael 
Published: May 2009

AbstractThymocytes from adult mice synthesize glucocorticoids (GCs), and some data indicate a role for this hormone production in thymic homeostasis. Here we present further support for this view by showing that the dramatic increase in thymocyte number seen after adrenalectomy (ADX) does not correlate with the decrease in systemic GCs but rather with an ACTH-mediated down-regulation of GC synthesis in thymocytes. High ACTH concentrations caused by ADX in wild-type mice down-regulated CYP11B1 mRNA expression, encoding the last enzyme required for corticosterone synthesis and as a consequence reduced GC synthesis in thymocytes. This was not seen in IL-1β/IL-18 double-knockout mice unable to respond to ADX with high ACTH levels. However, if ADX IL-1β/IL-18 double-knockout mice were treated with ACTH, this led to a down-regulation of CYP11B1 and GC synthesis in thymocytes. In addition, in vivo treatment of mice with the CYP11B1 antagonist metyrapone, without affecting the systemic corticosterone level, increased thymocyte numbers and in vitro treatment of isolated thymocytes prevented thymocyte loss. Furthermore, in vitro experiments showed that both ACTH and its receptor-induced second-messenger molecule cAMP down-regulated mRNA expression of critical enzymes in GC steroidogenesis and GC synthesis in thymocytes. We conclude that thymocyte-produced GCs are important for the homeostasis of adult mouse thymocytes and that high ACTH level, in contrast to stimulating GC synthesis in the adrenal glands, has the opposite effect in thymocytes.