bluuebunny/crossref_metadata_2025_split huggingface dataset:
Species-Specific Inhibition of Foamy Viruses from South American Monkeys by New World Monkey TRIM5α Proteins
Authors: Pacheco Beatriz , Finzi Andrés , McGee-Estrada Kathleen , Sodroski Joseph 
Published: February 2010

ABSTRACT
Foamy virus evolution closely parallels that of the host species, indicating virus-host coadaptation. We studied simian foamy viruses (SFVs) from common marmosets, spider monkeys, and squirrel monkeys, New World monkey (NWM) species that share geographic ranges. The TRIM5α protein from each of these NWM species inhibited the replication of at least one of the SFVs associated with the other two species but did not affect the replication of its own SFV. Thus, TRIM5α has potentially shaped the evolution of SFVs in NWM hosts. Conversely, SFVs may have influenced the evolution of TRIM5 variants in New World primates.
Skeletal age determination in adolescents involved in judicial procedures: from evidence-based principles to medical practice
Authors: Pruvost Marie-Odile , Boraud Cyril , Chariot Patrick 
Published: February 2010

BackgroundThe ideal basis of age estimation is considered to be a combination of clinical, skeletal and dental examinations. It is not easy to determine how forensic physicians take account of evidence-based data obtained from medical journals in their medical decision-making. The question of what is an ethically acceptable probability that adolescents are incorrectly considered to be over 18 has not been answered.MethodsIn a retrospective study over 1 year (2007), 498 files (for 141 female subjects and 357 male subjects) regarding age assessment requested by the public prosecutor's office for purposes of criminal or asylum proceedings were reviewed. Chronological age was estimated from a combination of physical examination, radiographic examination of the left hand and determination of dental status.ResultsEstimates of chronological age in 498 subjects claiming to be 9–14 years old were incompatible with the alleged age in 356 (71%) when made by the forensic physician but in only 17 (3%) when based on data from published studies on age estimation in adolescents.ConclusionsThe present study suggests that in most cases the forensic physician ignores the adolescent's word. Medical mission and ethics imply a need to listen to the claims of persons in custody, whatever the risk of false claims. This situation should prompt forensic physicians to keep up with published data on estimating the age of adolescents.
Clopidogrel non-responsiveness and risk of cardiovascular morbidity
Authors: Marcucci Rossella , Gori Anna Maria , Giusti Betti , Abbate Rosanna , Gensini Gian Franco , Sofi Francesco 
Published: February 2010

SummaryWe performed this meta-analysis to update the clinical evidences on the relation between clopidogrel non-responsiveness and clinical outcomes in patients with coronary artery disease (CAD) who underwent percutaneous coronary intervention. An electronic literature search through MEDLINE, EMBASE, Web of Science, and the Cochrane Library and bibliographies of retrieved articles up to January, 2009 was conducted. Studies were included if they had a cohort prospective design, if they analysed clopidogrel responsiveness in CAD patients in relation to death and/or occurrence of adverse coronary events during follow-up, and if they reported an adequate statistical analysis. Fourteen studies, totalling 4,564 CAD patients followed for a time ranging from 14 days to one year, were included. The cumulative analysis reported that residual platelet reactivity despite clopidogrel treatment was significantly associated with an increased risk of death and/or thrombotic recurrences (odds ratio [OR] 5.67, 95% confidence interval [CI] 2.97 to 10.84; p<0.00001). However, four studies contributed to a consistent heterogeneity of the model and evidenced a significant risk of publication bias, so were excluded from the analysis. This exclusion, however, did not influence the overall result, by confirming the increased risk of cardiovascular recurrences for patients with a poor response to clopidogrel treatment (OR 3.58, 95%CI 2.54 to 5.05; p<0.00001). The present updated meta-analysis documents a significant association between residual platelet reactivity under clopidogrel treatment and recurrent cardiovascular events, so suggesting the relevance of ongoing interventional studies aimed at tailoring the antithrombotic therapy in CAD patients.
Neuroserpin, a thrombolytic serine protease inhibitor (serpin), blocks transplant vasculopathy with associated modification of T-helper cell subsets
Authors: Munuswamy-Ramanujam Ganesh , Dai Erbin , Liu Liying , Shnabel Mira , Sun Yun Ming , Bartee Mee , Lomas David , Lucas Alexandra 
Published: February 2010

SummaryThrombolytic serine proteases not only initiate fibrinolysis, but also are up-regulated in vascular disease and acute inflammatory responses. Although the serine protease inhibitor (serpin) plasminogen activator inhibitor-1 (PAI-1) is considered a main regulator of thrombolysis, PAI-1 is also associated with vascular inflammation. The role of other serpins that target thrombolytic proteases, PAI-2, PAI-3, and neuroserpin (NSP), in vascular inflammation is, however, less well defined. NSP is a mammalian serpin that, similar to PAI-1, inhibits urokinase- and tissue-type plasminogen activators (uPA and tPA, respectively) and has been most closely associated with the nervous system, with a demonstrated protective role after cerebral infarction in mouse models. However, the role of NSP in systemic arterial inflammation and plaque growth is not known. Serp-1 is a myxoma viral serpin that also inhibits tPA and uPA, as well as additionally inhibiting plasmin and factor Xa (fXa). Serp-1 has proven highly potent anti-inflammatory and anti-atherogenic activity. Here we assess the effects of NSP treatment on plaque growth and T-helper (Th) lymphocyte activity in a mouse aortic allograft transplant model, with comparison to Serp-1. NSP and Serp-1 both significantly reduced plaque growth and T-cell invasion. T-bet (a Th1 differentiation marker) was significantly reduced in transplanted aorta with associated reductions in Th1 and Th17, but not Th2, in splenocytes. NSP had additional Th modifying activity in non-transplanted mice. In summary, this is the first report that NSP possesses anti-inflammatory activity in systemic arteries, modifying Th cell responses and significantly reducing plaque growth in mouse aortic allografts.
Prognostic value of plasma von Willebrand factor-cleaving protease (ADAMTS13) antigen levels in patients with coronary artery disease
Authors: Kaikita Koichi , Matsukawa Masakazu , Soejima Kenji , Fuchigami Shunichiro , Miyazaki Yuji , Ono Takamichi , Uemura Takashi , Tsujita Kenichi , Hokimoto Seiji , Sumida Hitoshi , Matsui Kunihiko , Yamabe Hiroshige , Ogawa Hisao , Miura Mitsutoshi 
Published: February 2010

SummaryHigh plasma level of von Willebrand factor (VWF) is a marker of future cardiovascular events in patients at high risk of coronary artery disease (CAD). The purpose of this study was to examine the changes and the prognostic value of plasma VWF-cleaving protease (ADAMTS13) levels in patients with CAD. Plasma VWF and ADAMTS13 levels were measured in 225 patients with CAD (152 men and 73 women, age, 70.3 ± 8.9 years, mean ± SD) and 100 patients without CAD who were ageand gender-matched to the CAD patients (60 men and 40 women, age, 68.6 ± 8.9 years). The CAD patients had higher VWF and lower ADAMTS13 antigen levels compared to patients without CAD. During 22.3 ± 10.4 months follow-up period, 20 major adverse cardiac and cerebrovascular events (MACCE) occurred in 222 patients with CAD who could be followed up. Kaplan-Meier analysis demonstrated that CAD patients with high plasma VWF antigen levels were significantly more likely to develop MACCE. Furthermore, eight cardiac and cerebrovascular thrombotic events [acute coronary syndrome (n=4) and cerebral infarction (n=4)] occurred in CAD patients with both high plasma VWF and low ADAMTS13 antigen levels. Multivariate Cox hazards regression analysis identified high plasma VWF and low ADAMTS13 antigen levels as significant and independent predictors of future MACCE and thrombotic events during the follow-up period in CAD patients. Our findings suggest that low plasma ADAMTS13 as well as high VWF level is a useful predictor of cardiac and cerebrovascular events in CAD patients.
Assessment of Parent-Adolescent Partnership in Diabetes Care
Authors: Beléndez Marina , de Wit Maartje , Snoek Frank J. 
Published: February 2010

Purpose To identify and evaluate psychometric properties of available measures to assess dimensions of parent-adolescent partnership in diabetes care, including parent-adolescent responsibility in diabetes management, parental monitoring, diabetes family conflict, and parental involvement. Methods A literature review that included searches of electronic databases from 1990 to April 2009 was conducted. Instruments were reviewed extracting information about aim, target population, and psychometric properties. Results Eight instruments were identified. Study samples appear to be large enough for psychometric validation but with a small proportion of fathers. The instruments have been designed and evaluated with adolescents and parents in the United States. Most of the instruments have adequate reliability, both for adolescents’ and parents’ forms. Regarding construct validity, factor structure of most of the instruments was evaluated either with exploratory factor analysis or confirmatory factor analysis. In addition, some measures have significant relationships with age in the direction expected or with other outcomes such as adherence or quality of life. Finally, all the reviewed studies are cross-sectional and have not yet addressed predictive validity or instrument responsiveness. Conclusions Valid measures tapping into aspects of diabetes-related adolescent-parent partnership are available, but longitudinal studies are needed to determine if the instruments are able to detect clinically significant change (eg, impact on metabolic control, adherence, quality of life). Rather than develop new measures, refinement and further validation of existing instruments is suggested.
1H and hyperpolarized 3He magnetic resonance imaging clearly detect the preventative effect of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo
Authors: Olsson Lars E. , Smailagic Amir , Önnervik Per-Ola , Lindén Anders , Hockings Paul D. 
Published: February 2010

Introduction: Proton (1H) magnetic resonance imaging (MRI) can be utilized to quantify pulmonary edema in endotoxin-induced pulmonary inflammation and hyperpolarized (HP) 3He MRI can assess pulmonary ventilation. Neither of the methods has been applied to assess the impact of a drug on endotoxin-induced pulmonary inflammation in vivo. The aim of the current study was to evaluate the capability of 1H and HP 3He MRI to assess the effects of a glucocorticoid on endotoxin-induced pulmonary inflammation in vivo. Materials and Methods: Mice were exposed to an aerosol of either saline or endotoxin (5 mg/ml) for 10 min. Half of the endotoxin-exposed mice were pretreated with a glucocorticoid (budesonide 3 mg/kg; 2 times/day) and the other half with vehicle p.o. The first budesonide treatment was administered 1 h prior to the aerosol inhalation. Forty-eight hours after the aerosol exposure, the mice were anaesthetized for subsequent imaging. Hyperpolarized 3He was administered and axial MR images of the lungs obtained. Matching 1H MR images were then acquired. The mice were sacrificed and broncho-alveolar lavage (BAL) samples were harvested to determine total and cell differential counts. Results: The lesion volume on both 1H and 3He MRI, were markedly increased by endotoxin exposure (P<0.001). Budesonide strongly reduced lesion volume ( P<0.001). The BAL cell count correlated strongly with both 3He ( P<0.001; r = 0.96) and 1H lesion volumes ( P<0.001; r = 0.97). Conclusions: Hyperpolarized 3He MRI and 1H MRI clearly visualized the preventative effect of budesonide on the impact of endotoxin on pulmonary ventilation and edema, respectively. The fact that ventilation defects on 3He MRI corresponded to findings from conventional 1H MRI, as well as to counts of BAL inflammatory cells suggests that these imaging techniques constitute promising tools for non-invasive monitoring of pulmonary inflammation in vivo.
The post sepsis-induced expansion and enhanced function of regulatory T cells create an environment to potentiate tumor growth
Authors: Cavassani Karen A. , Carson William F. , Moreira Ana Paula , Wen Haitao , Schaller Matthew A. , Ishii Makoto , Lindell Dennis M. , Dou Yali , Lukacs Nicholas W. , Keshamouni Venkateshwar G. , Hogaboam Cory M. , Kunkel Steven L. 
Published: February 2010

AbstractOne of the more insidious outcomes of patients who survive severe sepsis is profound immunosuppression. In this study, we addressed the hypothesis that post septic immune defects were due, in part, to the presence and/or expansion of regulatory T cells (Tregs). After recovery from severe sepsis, mice exhibited significantly higher numbers of Tregs, which exerted greater in vitro suppressive activity compared with controls. The expansion of Tregs was not limited to CD25+ cells, because Foxp3 expression was also detected in CD25− cells from post septic mice. This latter group exhibited a significant increase of chromatin remodeling at the Foxp3 promoter, because a marked increase in acetylation at H3K9 was associated with an increase in Foxp3 transcription. Post septic splenic dendritic cells promoted Treg conversion in vitro. Using a solid tumor model to explore the function of Tregs in an in vivo setting, we found post septic mice showed an increase in tumor growth compared with sham-treated mice with a syngeneic tumor model. This observation could mechanistically be related to the ability of post septic Tregs to impair the antitumor response mediated by CD8+ T cells. Together, these data show that the post septic immune system obstructs tumor immunosurveillance, in part, by augmented Treg expansion and function.
The role of tumor histogenesis, FDG-PET, and short-course EPOCH with dose-dense rituximab (SC-EPOCH-RR) in HIV-associated diffuse large B-cell lymphoma
Authors: Dunleavy Kieron , Little Richard F. , Pittaluga Stefania , Grant Nicole , Wayne Alan S. , Carrasquillo Jorge A. , Steinberg Seth M. , Yarchoan Robert , Jaffe Elaine S. , Wilson Wyndham H. 
Published: February 2010

AbstractThis is a phase 2 study to assess the role of tumor histogenesis (subtype), fluorodeoxyglucose positron emission tomography (FDG-PET), and short-course etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin with dose-dense rituximab (SC-EPOCH-RR) in newly diagnosed HIV-associated CD20+ diffuse large B-cell lymphoma. Patients received a minimum of 3 and a maximum of 6 cycles with 1 cycle beyond stable radiographic and FDG-PET scans. Overall, 79% of patients received 3 cycles. Combination antiretroviral therapy was suspended before and resumed after therapy. Thirty-three enrolled patients had a median age of 42 years (range, 9-61 years), and 76% had a high-intermediate or high age-adjusted international prognostic index. At 5 years median follow-up, progression-free and overall survival were 84% and 68%, respectively. There were no treatment-related deaths or new opportunistic infections during treatment, and patients had sustained CD4 cell count recovery and HIV viral control after treatment. FDG-PET after 2 cycles had an excellent negative but poor positive predictive value. Tumor histogenesis was the only characteristic associated with lymphoma-specific outcome with 95% of germinal center B-cell (GCB) versus 44% of non-GCB diffuse large B-cell lymphoma (DLBCL) progression-free at 5 years. SC-EPOCH-RR is highly effective and less immunosuppressive with shorter duration therapy compared with standard strategies. However, new therapeutic advances are needed for non-GCB DLBCL, which remains the important cause of lymphoma-specific death. This trial was registered at www.clinicaltrials.gov as NCT000019253.
Targeting human telomerase reverse transcriptase with recombinant lentivector is highly effective to stimulate antitumor CD8 T-cell immunity in vivo
Authors: Adotévi Olivier , Mollier Karine , Neuveut Christine , Dosset Magalie , Ravel Patrice , Fridman Wolf-Hervé , Tartour Eric , Charneau Pierre , Wain-Hobson Simon , Langlade-Demoyen Pierre 
Published: February 2010

AbstractThe success of active immunotherapy is based on the vaccine's ability to overcome immune tolerance through recalibrating the immune system so that it is able to recognize tumor antigens as foreign rather than self. In this study, we used a lentiviral vector system to target human telomerase reverse transcriptase (lv-hTERT), a widely expressed tumor antigen. Immunization of HLA-A*0201 transgenic HHD mice with recombinant lv-hTERT vector induces potent and diversified cytotoxic T lymphocyte responses that recognize in vitro murine tumor cells, which overexpress telomerase. Compared with peptide-based vaccinations, the lv-hTERT vector triggers better and more sustained CD8+ T-cell response against self/TERT epitope in vivo. The study found that the additional use of a heterologous boosted vaccination drastically improves self/TERT-specific CD8 responses in lv-hTERT primed mice. Both primary and long-lasting self/TERT-specific CD8+ T-cell responses induced with Iv-hTERT vector required the presence of CD4 T cells in vivo. This lv-hTERT–based active immunotherapy efficiently inhibits the growth of telomerase expressing tumors (B16/HLA-A2.1 murine melanoma) in HHD mice. These data show that targeting hTERT with lentivector is highly effective in stimulating a broad range of CD8 T-cell immunity that can be exploited for cancer immunotherapy.
Caldesmon regulates the motility of vascular smooth muscle cells by modulating the actin cytoskeleton stability
Authors: Jiang Qifeng , Huang Renjian , Cai Shaoxi , Wang Chih-Lueh A 
Published: February 2010

Abstract

Background
Migration of vascular smooth muscle cells (SMCs) from the media to intima constitutes a critical step in the development of proliferative vascular diseases. To elucidate the regulatory mechanism of vacular SMC motility, the roles of caldesmon (CaD) and its phosphorylation were investigated.

Methods
We have performed Transwell migration assays, immunofluorescence microscopy, traction microscopy and cell rounding assays using A7r5 cells transfected with EGFP (control), EGFP-wtCaD or phosphomimetic CaD mutants, including EGFP-A1A2 (the two PAK sites Ser452 and Ser482 converted to Ala), EGFP-A3A4 (the two Erk sites Ser497 and Ser527 converted to Ala), EGFP-A1234 (both PAK- and Erk-sites converted to Ala) and EGFP-D1234 (both PAK- and Erk-sites converted to Asp).

Results
We found that cells transfected with wtCaD, A1A2 or A3A4 mutants of CaD migrated at a rate approximately 50% more slowly than those EGFP-transfected cells. The migration activity for A1234 cells was only about 13% of control cells. Thus it seems both MAPK and PAK contribute to the motility of A7r5 cells and the effects are comparable and additive. The A1234 mutant also gave rise to highest strain energy and lowest rate of cell rounding. The migratory and contractile properties of these cells are consistent with stabilized actin cytoskeletal structures. Indeed, the A1234 mutant cells exhibited most robust stress fibers, whereas cells transfected with wtCaD or A3A4 (and A1A2) had moderately reinforced actin cytoskeleton. The control cells (transfected with EGFP alone) exhibited actin cytoskeleton that was similar to that in untransfected cells, and also migrated at about the same speed as the untransfected cells.

Conclusions
These results suggest that both the expression level and the level of MAPK- and/or PAK-mediated phosphorylation of CaD play key roles in regulating the cell motility by modulating the actin cytoskeleton stability in dedifferentiated vascular SMCs such as A7r5.
Seatbelt syndrome associated with an isolated rectal injury: case report
Authors: Hefny Ashraf F , Al-Ashaal Yousef I , Bani-Hashem Ahmed M , Abu-Zidan Fikri M 
Published: February 2010

AbstractSeatbelt syndrome is defined as a seatbelt sign associated with a lumbar spine fracture and a bowel perforation. An isolated rectal perforation due to seatbelt syndrome is extremely rare. There is only one case reported in the Danish literature and non in the English literature. A 48-year old front seat restrained passenger was involved in a head-on collision. He had lower abdominal pain and back pain. Seatbelt mark was seen across the lower abdomen. Initial trauma CT scan was normal except for a burst fracture of L5 vertebra which was operated on by internal fixation on the same day. The patient continued to have abdominal pain. A repeated abdominal CT scan on the third day has shown free intraperitoneal air. Laparotomy has revealed a perforation of the proximal part of the rectum below the recto sigmoid junction. Hartmann's procedure was performed. The abdomen was left open. Gradual closure of the abdominal fascia over a period of two weeks was performed. Postoperatively, the patient had temporary urinary retention due to quada equina injury which resolved 10 months after surgery. The presence of a seatbelt sign and a lumbar fracture should raise the possibility of a bowel injury.
Scanning mutagenesis of the I-II loop of the Cav2.2 calcium channel identifies residues Arginine 376 and Valine 416 as molecular determinants of voltage dependent G protein inhibition
Authors: Tedford Hugo W , Kisilevsky Alexandra E , Vieira Lucienne B , Varela Diego , Chen Lina , Zamponi Gerald W 
Published: February 2010

AbstractDirect interaction with the β subunit of the heterotrimeric G protein complex causes voltage-dependent inhibition of N-type calcium channels. To further characterize the molecular determinants of this interaction, we performed scanning mutagenesis of residues 372-387 and 410-428 of the N-type channel α1subunit, in which individual residues were replaced by either alanine or cysteine. We coexpressed wild type Gβ1γ2subunits with either wild type or point mutant N-type calcium channels, and voltage-dependent, G protein-mediated inhibition of the channels (VDI) was assessed using patch clamp recordings. The resulting data indicate that Arg376and Val416of the α1subunit, residues which are surface-exposed in the presence of the calcium channel β subunit, contribute significantly to the functional inhibition by Gβ1. To further characterize the roles of Arg376and Val416in this interaction, we performed secondary mutagenesis of these residues, coexpressing the resulting mutants with wild type Gβ1γ2subunits and with several isoforms of the auxiliary β subunit of the N-type channel, again assessing VDI using patch clamp recordings. The results confirm the importance of Arg376for G protein-mediated inhibition and show that a single amino acid substitution to phenylalanine drastically alters the abilities of auxiliary calcium channel subunits to regulate G protein inhibition of the channel.