bluuebunny/crossref_metadata_2025_split huggingface dataset:
Complications Associated With the Arterial Puncture Closure Device—Angio-Seal
Authors: Kadner Alexander , Schmidli Jürg , Schwegler Igor , Dick Florian , Schönhoff Florian , Carrel Thierry , Savolainen Hannu 
Published: January 2008

Background Arterial puncture closure devices (APCD) are frequently used after cardiac catheterization. Here, the diagnosis and therapy of femoral artery complications after the use of the Angio-Seal APCD is reported. Patients and methods The Angio-Seal APCD was deployed in 1600 patients undergoing transfemoral catheterization. Results In 7 of 1600 cases (0.4%) vascular complications occurred following Angio-Seal deployment. Diagnosis was made by duplex sonography. Intraoperative findings consisted of a complete occlusion with dissection of the femoral artery in all patients. In 6 cases, the femoral bifurcation had to be reconstructed after endarterectomy. Follow-up is complete with a mean of 6 months. Conclusion The Angio-Seal device should not be used for closure of the superficial femoral artery and in patients with severe arteriosclerosis. The application of arteriography as well as the use of ultrasound-guided puncture is advisable. In all cases, surgical intervention was successful and an adequate therapy for management of complications.
PEPOP: Computational design of immunogenic peptides
Authors: Moreau Violaine , Fleury Cécile , Piquer Dominique , Nguyen Christophe , Novali Nicolas , Villard Sylvie , Laune Daniel , Granier Claude , Molina Franck 
Published: January 2008

AbstractBackgroundMost methods available to predict protein epitopes are sequence based. There is a need for methods using 3D information for prediction of discontinuous epitopes and derived immunogenic peptides.ResultsPEPOP uses the 3D coordinates of a protein both to predict clusters of surface accessible segments that might correspond to epitopes and to design peptides to be used to raise antibodies that target the cognate antigen at specific sites. To verify the ability of PEPOP to identify epitopes, 13 crystallographically defined epitopes were compared with PEPOP clusters: specificity ranged from 0.75 to 1.00, sensitivity from 0.33 to 1.00, and the positive predictive value from 0.19 to 0.89. Comparison of these results with those obtained with two other prediction algorithms showed comparable specificity and slightly better sensitivity and PPV. To prove the capacity of PEPOP to predict immunogenic peptides that induce protein cross-reactive antibodies, several peptides were designed from the 3D structure of model antigens (IA-2, TPO, and IL8) and chemically synthesized. The reactivity of the resulting anti-peptides antibodies with the cognate antigens was measured. In 80% of the cases (four out of five peptides), the flanking protein sequence process (sequence-based) of PEPOP successfully proposed peptides that elicited antibodies cross-reacting with the parent proteins. Polyclonal antibodies raised against peptides designed from amino acids which are spatially close in the protein, but separated in the sequence, could also be obtained, although they were much less reactive. The capacity of PEPOP to design immunogenic peptides that induce antibodies suitable for a sandwich capture assay was also demonstrated.ConclusionPEPOP has the potential to guide experimentalists that want to localize an epitope or design immunogenic peptides for raising antibodies which target proteins at specific sites. More successful predictions of immunogenic peptides were obtained when a peptide was continuous as compared with peptides corresponding to discontinuous epitopes. PEPOP is available for use athttp://diagtools.sysdiag.cnrs.fr/PEPOP/.
Genome-wide transcriptome analysis reveals that a pleiotropic antibiotic regulator, AfsS, modulates nutritional stress response in Streptomyces coelicolor A3(2)
Authors: Lian Wei , Jayapal Karthik P , Charaniya Salim , Mehra Sarika , Glod Frank , Kyung Yun-Seung , Sherman David H , Hu Wei-Shou 
Published: January 2008

Abstract

Background
A small "sigma-like" protein, AfsS, pleiotropically regulates antibiotic biosynthesis in Streptomyces coelicolor. Overexpression of afsS in S. coelicolor and certain related species causes antibiotic stimulatory effects in the host organism. Although recent studies have uncovered some of the upstream events activating this gene, the mechanisms through which this signal is relayed downstream leading to the eventual induction of antibiotic pathways remain unclear.

Results
In this study, we employed whole-genome DNA microarrays and quantitative PCRs to examine the transcriptome of an afsS disruption mutant that is completely deficient in the production of actinorhodin, a major S. coelicolor antibiotic. The production of undecylprodigiosin, another prominent antibiotic, was, however, perturbed only marginally in the mutant. Principal component analysis of temporal gene expression profiles identified two major gene classes each exhibiting a distinct coordinate differential expression pattern. Surprisingly, nearly 70% of the >117 differentially expressed genes were conspicuously associated with nutrient starvation response, particularly those of phosphate, nitrogen and sulfate. Furthermore, expression profiles of some transcriptional regulators including at least two sigma factors were perturbed in the mutant. In almost every case, the effect of afsS disruption was not observed until the onset of stationary phase.

Conclusion
Our data suggests a comprehensive role for S. coelicolor AfsS as a master regulator of both antibiotic synthesis and nutritional stress response, reminiscent of alternative sigma factors found in several bacteria.
Heme rescues a two-component system Leptospira biflexa mutant
Authors: Louvel Hélène , Betton Jean-Michel , Picardeau Mathieu 
Published: January 2008

Abstract

Background
Heme is typically a major iron source for bacteria, but little is known about how bacteria of the Leptospira genus, composed of both saprophytic and pathogenic species, access heme.

Results
In this study, we analysed a two-component system of the saprophyte Leptospira biflexa. In vitro phosphorylation and site-directed mutagenesis assays showed that Hklep is a histidine kinase which, after autophosphorylation of a conserved histidine, transfers the phosphate to an essential aspartate of the response regulator Rrlep. Hklep/Rrlep two-component system mutants were generated in L. biflexa. The mutants could only grow in medium supplemented with hemin or δ-aminolevulinic acid (ALA). In the pathogen L. interrogans, the hklep and rrlep orthologous genes are located between hemE and hemL genes, which encode proteins involved in heme biosynthesis. The L. biflexa hklep mutant could be complemented with a replicative plasmid harbouring the L. interrogans orthologous gene, suggesting that these two-component systems are functionally similar. By real-time quantitative reverse transcription-PCR, we also observed that this two-component system might influence the expression of heme biosynthetic genes.

Conclusion
These findings demonstrate that the Hklep/Rrlep regulatory system is critical for the in vitro growth of L. biflexa, and suggest that this two-component system is involved in a complex mechanism that regulates the heme biosynthetic pathway.
Complementary or alternative? The use of homeopathic products and antibiotics amongst pre-school children
Authors: Wye Lesley , Hay Alastair D , Northstone Kate , Bishop Jackie , Headley Judith , Thompson Elizabeth 
Published: January 2008

Abstract

Background
Any intervention to reduce the inappropriate use of antibiotics for infections in children has the potential to reduce the selective pressure on antimicrobial resistance and minimise the medicalisation of self-limiting illness. Little is known about whether homeopathic products might be used by some families as an alternative to antibiotics or the characteristics of such families. We used the Avon Longitudinal Study of Parents and Children (ALSPAC) observational dataset to explore the hypothesis that the use of homeopathic products is associated with reduced antibiotic use in pre-school children and to identify characteristics of the families of pre-school children given homeopathic products.

Methods
Questionnaires data were completed by the parents of 9723 children while aged between 3–4.5 years in Bristol UK. Univariable and multivariable analyses were used to explore the relationships between antibiotic and homeopathic product use.

Results
Six percent of children had received one or more homeopathic products and 62% one or more antibiotics between the ages of 3 and 4.5 years. After adjustment for factors associated with antibiotic use, there was no association between homeopathic product and antibiotic use (adjusted OR = 1.02, 95% CI 0.84, 1.24). Factors independently associated with child homeopathic product use were: higher maternal education, maternal use of homeopathic products, maternal lack of confidence in doctors, mothers reporting that they were less likely to see doctor when the child was ill, children being given vitamins, watching less television and suffering from wheeze and food allergies.

Conclusion
In this observational study, the use of homeopathic products was not associated with decreased antibiotic consumption, suggesting the use of homeopathic product complements rather than competes with the use of antibiotics in pre-school children. The characteristics of mothers giving homeopathic products to their children are similar to those associated with adult self-administration.
Importance of TP53 codon 72 and intron 3 duplication 16bppolymorphisms in prediction of susceptibility on breast cancer
Authors: Costa Sandra , Pinto Daniela , Pereira Deolinda , Rodrigues Helena , Cameselle-Teijeiro Jorge , Medeiros Rui , Schmitt Fernando 
Published: January 2008

Abstract

Background

TP53 is one of major tumour suppressor genes being essential in preservation of genome integrity. Two very common polymorphisms have been demonstrated to contribute to cancer susceptibility and tumour behaviour. The purpose of this study was to evaluate the role of Arg72Pro and PIN3 Ins16bp polymorphisms in TP53 gene as genetic susceptibility and predictive markers to breast cancer.

Methods
We analysed DNA samples from 264 breast cancer patients and 440 controls, for TP53 Arg72Pro and PIN3 Ins16bp polymorphisms using PCR-RFLP.

Results
We observed that women with A2A2 genotype have increased risk for developing breast cancer, either in women with or without familial history (FH) of the disease (OR = 4.40, 95% CI 1.60–12.0; p = 0.004; OR = 3.88, 95% CI 1.18–12.8; p = 0.026, respectively). In haplotype analysis, statistically significant differences were found between TP53 Arg-A2 haplotype frequencies and familial breast cancer cases and the respective control group (OR = 2.10, 95% CI 1.08–4.06; p = 0.028). Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases.

Conclusion
Our findings suggest TP53 PIN3 Ins16bp polymorphism as a real risk modifier in breast cancer disease, either in sporadic and familial breast cancer. Furthermore, both TP53 polymorphisms are associated with higher incidence of lymph node metastases.
Fast dynamics perturbation analysis for prediction of protein functional sites
Authors: Ming Dengming , Cohn Judith D , Wall Michael E 
Published: January 2008

Abstract

Background
We present a fast version of the dynamics perturbation analysis (DPA) algorithm to predict functional sites in protein structures. The original DPA algorithm finds regions in proteins where interactions cause a large change in the protein conformational distribution, as measured using the relative entropy D

x
. Such regions are associated with functional sites.

Results
The Fast DPA algorithm, which accelerates DPA calculations, is motivated by an empirical observation that D

x
in a normal-modes model is highly correlated with an entropic term that only depends on the eigenvalues of the normal modes. The eigenvalues are accurately estimated using first-order perturbation theory, resulting in a N-fold reduction in the overall computational requirements of the algorithm, where N is the number of residues in the protein. The performance of the original and Fast DPA algorithms was compared using protein structures from a standard small-molecule docking test set. For nominal implementations of each algorithm, top-ranked Fast DPA predictions overlapped the true binding site 94% of the time, compared to 87% of the time for original DPA. In addition, per-protein recall statistics (fraction of binding-site residues that are among predicted residues) were slightly better for Fast DPA. On the other hand, per-protein precision statistics (fraction of predicted residues that are among binding-site residues) were slightly better using original DPA. Overall, the performance of Fast DPA in predicting ligand-binding-site residues was comparable to that of the original DPA algorithm.

Conclusion
Compared to the original DPA algorithm, the decreased run time with comparable performance makes Fast DPA well-suited for implementation on a web server and for high-throughput analysis.
Malaria in central Vietnam: analysis of risk factors by multivariate analysis and classification tree models
Authors: Thang Ngo Duc , Erhart Annette , Speybroeck Niko , Hung Le Xuan , Thuan Le Khanh , Hung Cong Trinh , Ky Pham Van , Coosemans Marc , D'Alessandro Umberto 
Published: January 2008

Abstract

Background
In Central Vietnam, forest malaria remains difficult to control due to the complex interactions between human, vector and environmental factors.

Methods
Prior to a community-based intervention to assess the efficacy of long-lasting insecticidal hammocks, a complete census (18,646 individuals) and a baseline cross-sectional survey for determining malaria prevalence and related risk factors were carried out. Multivariate analysis using survey logistic regression was combined to a classification tree model (CART) to better define the relative importance and inter-relations between the different risk factors.

Results
The study population was mostly from the Ra-glai ethnic group (88%), with both low education and socio-economic status and engaged mainly in forest activities (58%). The multivariate analysis confirmed forest activity, bed net use, ethnicity, age and education as risk factors for malaria infections, but could not handle multiple interactions. The CART analysis showed that the most important risk factor for malaria was the wealth category, the wealthiest group being much less infected (8.9%) than the lower and medium wealth category (16.6%). In the former, forest activity and bed net use were the most determinant risk factors for malaria, while in the lower and medium wealth category, insecticide treated nets were most important, although the latter were less protective among Ra-glai people.

Conclusion
The combination of CART and multivariate analysis constitute a novel analytical approach, providing an accurate and dynamic picture of the main risk factors for malaria infection. Results show that the control of forest malaria remains an extremely complex task that has to address poverty-related risk factors such as education, ethnicity and housing conditions.
Prostasome-like vesicles stimulate acrosome reaction of pig spermatozoa
Authors: Siciliano Laura , Marcianò Vito , Carpino Amalia 
Published: January 2008

Abstract

Background
The presence of small membranous particles characterizes the male genital fluids of different mammalian species. The influence of semen vesicles, denominated prostasomes, on sperm functional properties has been well documented in humans, but their biological activity is scarcely known in other species. The present work investigated prostasome-like vesicles in pig semen for their ability to interact with spermatozoa and to affect acrosome reaction.

Methods
Prostasome-like vesicles have been isolated from pig seminal plasma by high-speed centrifugation and Sephadex G-200 gel chromatography. Morphology of purified vesicles has been checked by scanning electron microscopy while their protein pattern has been investigated by SDS-PAGE. Then prostasome- like vesicles have been incubated with pig spermatozoa and their ability to interact with sperm has been tested by the aminopeptidase assay. In addition, the efficiency of vesicles to influence the acrosome reaction has been investigated by assessing the sperm acrosomal status by the PI/FITC-PNA (propidium iodide/fluorescein isothiocyanate-labeled peanut agglutinin) stainings.

Results
Purified vesicles revealed a complex protein pattern with the occurrence of bands in the high, medium and low molecular weight range. However, the two major bands were observed at ~90 kDa and ~60 kDa. A vesicle-mediated transfer of aminopeptidase to sperm cells has been also detected. Furthermore, a significant increase of acrosome reaction extent has been revealed in spermatozoa incubated with prostasome-like vesicles in comparison to control sperm.

Conclusion
This is the first report demonstrating that pig prostasome-like vesicles are able, in vitro, to interact with spermatozoa and to stimulate the acrosome reaction. These findings lead to hypothesize a transfer of molecules from vesicles to sperm membrane, thus sensitizing male gametes to undergo the acrosome reaction
Complement anaphylatoxin C5a neuroprotects through regulation of glutamate receptor subunit 2 in vitro and in vivo
Authors: Mukherjee Piali , Thomas Sunil , Pasinetti Giulio Maria 
Published: January 2008

AbstractBackgroundThe complement system is thought to be involved in the pathogenesis of numerous neurological diseases. We previously reported that pre-treatment of murine cortico-hippocampal neuronal cultures with the complement derived anaphylatoxin C5a, protects against glutamate mediated apoptosis. Our present study with C5a receptor knock out (C5aRKO) mice corroborates that the deficiency of C5a renders C5aRKO mouse more susceptible to apoptotic injuryin vivo. In this study we explored potential upstream mechanisms involved in C5a mediated neuroprotectionin vivoandin vitro.MethodsBased on evidence suggesting that reduced expression of glutamate receptor subunit 2 (GluR2) may influence apoptosis in neurons, we studied the effect of human recombinant C5a on GluR2 expression in response to glutamate neurotoxicity. Glutamate analogs were injected into C5aRKO mice or used to treatin vitroneuronal culture and GluR2 expression were assessed in respect with cell death.ResultsIn C5aRKO mice we found that the neurons are more susceptible to excitotoxicity resulting in apoptotic injury in the absence of the C5a receptor compared to WT control mice. Our results suggest that C5a protects against apoptotic pathways in neuronsin vitroandin vivothrough regulation of GluR2 receptor expression.ConclusionComplement C5a neuroprotects through regulation of GluR2 receptor subunit.
Cartilage preservation by inhibition of Janus kinase 3 in two rodent models of rheumatoid arthritis
Authors: Milici Anthony J , Kudlacz Elizabeth M , Audoly Laurent , Zwillich Samuel , Changelian Paul 
Published: January 2008

Abstract
Introduction
CP-690550 is a small molecule inhibitor of Janus kinase 3 (JAK3), a critical enzyme in the signaling pathway of multiple cytokines (interleukin (IL)-2, -7, -15 and -21) that are important in various T cell functions including development, activation and homeostasis. The purpose of this study was to evaluate CP-690550 in murine collagen-induced (CIA) and rat adjuvant-induced (AA) models of rheumatoid arthritis (RA).

Methods
CIA and AA were induced using standard protocols and animals received the JAK3 inhibitor via osmotic mini-pump infusion at doses ranging from 1.5–15 mg/kg/day following disease induction. Arthritis was assessed by clinical scores in the CIA models and paw swelling monitored using a plethysmometer in the AA model until study conclusion, at which time animals were killed and evaluated histologically.

Results
CP-690550 dose-dependently decreased endpoints of disease in both RA models with greater than 90% reduction observed at the highest administered dose. An approximate ED50 of approximately 1.5 mg/kg/day was determined for the compound based upon disease endpoints in both RA models examined and corresponds to CP-690550 serum levels of 5.8 ng/ml in mice (day 28) and 24 ng/ml in rats (day 24). The compound also reduced inflammatory cell influx and joint damage as measured histologically. Animals receiving a CP-690550 dose of 15 mg/k/d showed no histological evidence of disease.

Conclusion
The efficacy observed with CP-690550 in CIA and AA suggests JAK3 inhibition may represent a novel therapeutic target for the treatment of RA.
Phase I and Pharmacokinetic Study of Imatinib Mesylate in Patients With Advanced Malignancies and Varying Degrees of Liver Dysfunction: A Study by the National Cancer Institute Organ Dysfunction Working Group
Authors: Ramanathan Ramesh K. , Egorin Merrill J. , Takimoto Chris H.M. , Remick Scot C. , Doroshow James H. , LoRusso Patricia A. , Mulkerin Daniel L. , Grem Jean L. , Hamilton Anne , Murgo Anthony J. , Potter Douglas M. , Belani Chandra P. , Hayes Michael J. , Peng Bin , Ivy S. Percy 
Published: January 2008

Purpose To develop dosing guidelines and to evaluate the pharmacokinetics of imatinib in patients with liver dysfunction (LD). Patients and Methods Patients (N = 89) with varying solid tumors and liver function were stratified into four groups according to serum total bilirubin and AST and were treated with escalating doses of imatinib. Plasma and urine were assayed for concentrations of imatinib and its active metabolite, CGP74588 . Results In the mild LD group, dose-limiting toxicity, specifically nausea/vomiting and fatigue, occurred in two patients at the 600 mg/d dose level. In the moderate and severe LD groups, the maximal dose evaluated was 300 mg/d. Grade 3 to 4 toxicities consisted primarily of liver function test elevations (24%), nausea/vomiting (10%), fatigue (6%), and edema (5%). After the first imatinib dose, the mean (± SD) dose-normalized areas under the plasma concentration-time curve from time 0 to infinity (AUC0-∞) were 162 ± 155, 171 ± 72, 182 ± 157, and 185 ± 172 (μg/mL × h)/mg for normal, mild, moderate, and severe LD groups, respectively. Renal excretion of imatinib was less than 10% of the total dose in all groups. Conclusion Imatinib exposure (as measured by the dose-normalized AUC) did not differ between patients with normal liver function and those with LD. The maximal recommended dose of imatinib for patients with mild LD is 500 mg/d. Dosing guidelines for patients with moderate and severe LD remain undetermined.