bluuebunny/crossref_metadata_2025_split huggingface dataset:
Characterization and Serologic Analysis of theTreponema pallidumProteome
Authors: McGill Melanie A. , Edmondson Diane G. , Carroll James A. , Cook Richard G. , Orkiszewski Ralph S. , Norris Steven J. 
Published: April 2010

ABSTRACTTreponema pallidumsubsp. pallidumis the causative agent of syphilis, a sexually transmitted disease characterized by widespread tissue dissemination and chronic infection. In this study, we analyzed the proteome ofT. pallidumby the isoelectric focusing (IEF) and nonequilibrating pH gel electrophoresis (NEPHGE) forms of two-dimensional gel electrophoresis (2DGE), coupled with matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) analysis. We determined the identity of 148T. pallidumprotein spots, representing 88T. pallidumpolypeptides; 63 of these polypeptides had not been identified previously at the protein level. To examine which of these proteins are important in the antibody response to syphilis, we performed immunoblot analysis using infected rabbit sera or human sera from patients at different stages of syphilis infection. Twenty-nine previously described antigens (predominantly lipoproteins) were detected, as were a number of previously unidentified antigens. The reactivity patterns obtained with sera from infected rabbits and humans were similar; these patterns included a subset of antigens reactive with all serum samples tested, including CfpA, MglB-2, TmpA, TmpB, flagellins, and the 47-kDa, 17-kDa, and 15-kDa lipoproteins. A unique group of antigens specifically reactive with infected human serum was also identified and included the previously described antigen TpF1 and the hypothetical proteins TP0584, TP0608, and TP0965. This combined proteomic and serologic analysis further delineates the antigens potentially useful as vaccine candidates or diagnostic markers and may provide insight into the host-pathogen interactions that occur duringT. palliduminfection.
Milestones in Progression of Primary Pneumonic Plague in Cynomolgus Macaques
Authors: Koster Frederick , Perlin David S. , Park Steven , Brasel Trevor , Gigliotti Andrew , Barr Edward , Myers Leslie , Layton Robert C. , Sherwood Robert , Lyons C. R. 
Published: April 2010

ABSTRACT

Vaccines against primary pneumonic plague, a potential bioweapon, must be tested for efficacy in well-characterized nonhuman primate models. Telemetered cynomolgus macaques (
Macaca fascicularis
) were challenged by the aerosol route with doses equivalent to approximately 100 50% effective doses of
Yersinia pestis
strain CO92 and necropsied at 24-h intervals postexposure (p.e.). Data for telemetered heart rates, respiratory rates, and increases in the temperature greater than the diurnal baseline values identified the onset of the systemic response at 55 to 60 h p.e. in all animals observed for at least 70 h p.e. Bacteremia was detected at 72 h p.e. by a
Yersinia
16S rRNA-specific quantitative reverse transcription-PCR and was detected later by the culture method at the time of moribund necropsy. By 72 h p.e. multilobar pneumonia with diffuse septal inflammation consistent with early bacteremia was established, and all lung tissues had a high bacterial burden. The levels of cytokines or chemokines in serum were not significantly elevated at any time, and only the interleukin-1β, CCL2, and CCL3 levels were elevated in lung tissue. Inhalational plague in the cynomolgus macaque inoculated by the aerosol route produces most clinical features of the human disease, and in addition the disease progression mimics the disease progression from the anti-inflammatory phase to the proinflammatory phase described for the murine model. Defined milestones of disease progression, particularly the onset of fever, tachypnea, and bacteremia, should be useful for evaluating the efficacy of candidate vaccines.
Virulence Gene Regulation by CvfA, a Putative RNase: the CvfA-Enolase Complex inStreptococcus pyogenesLinks Nutritional Stress, Growth-Phase Control, and Virulence Gene Expression
Authors: Kang Song Ok , Caparon Michael G. , Cho Kyu Hong 
Published: April 2010

ABSTRACTStreptococcus pyogenes, a multiple-auxotrophic human pathogen, regulates virulence gene expression according to nutritional availability during various stages in the infection process or in different infection sites. We discovered that CvfA influenced the expression of virulence genes according to growth phase and nutritional status. The influence of CvfA in C medium, rich in peptides and poor in carbohydrates, was most pronounced at the stationary phase. Under these conditions, up to 30% of the transcriptome exhibited altered expression; the levels of expression of multiple virulence genes were altered, including the genes encoding streptokinase, CAMP factor, streptolysin O, M protein (more abundant in the CvfA−mutant), SpeB, mitogenic factor, and streptolysin S (less abundant). The increase of carbohydrates or peptides in media restored the levels of expression of the virulence genes in the CvfA−mutant to wild-type levels (emm,ska, andcfaby carbohydrates;speBby peptides). Even though the regulation of gene expression dependent on nutritional stress is commonly linked to the stringent response, the levels of ppGpp were not altered by deletion ofcvfA. Instead, CvfA interacted with enolase, implying that CvfA, a putative RNase, controls the transcript decay rates of virulence factors or their regulators according to nutritional status. The virulence of CvfA−mutants was highly attenuated in murine models, indicating that CvfA-mediated gene regulation is necessary for the pathogenesis ofS. pyogenes. Taken together, the CvfA-enolase complex inS. pyogenesis involved in the regulation of virulence gene expression by controlling RNA degradation according to nutritional stress.
Role of Lipid A Acylation in
Yersinia enterocolitica
Virulence
Authors: Pérez-Gutiérrez Camino , Llobet Enrique , Llompart Catalina M. , Reinés Mar , Bengoechea José A. 
Published: April 2010

ABSTRACT

Yersinia enterocolitica
is an important human pathogen.
Y. enterocolitica
must adapt to the host environment, and temperature is an important cue regulating the expression of most
Yersinia
virulence factors. Here, we report that
Y. enterocolitica
8081 serotype O:8 synthesized tetra-acylated lipid A at 37°C but that hexa-acylated lipid A predominated at 21°C. By mass spectrometry and genetic methods, we have shown that the
Y. enterocolitica msbB
,
htrB
, and
lpxP
homologues encode the acyltransferases responsible for the addition of C
12
, C
14
and C
16:1
, respectively, to lipid A. The expression levels of the acyltransferases were temperature regulated. Levels of expression of
msbB
and
lpxP
were higher at 21°C than at 37°C, whereas the level of expression of
htrB
was higher at 37°C. At 21°C, an
lpxP
mutant was the strain most susceptible to polymyxin B, whereas at 37°C, an
htrB
mutant was the most susceptible. We present evidence that the lipid A acylation status affects the expression of
Yersinia
virulence factors. Thus, expression of
flhDC
, the flagellar master regulatory operon, was downregulated in
msbB
and
lpxP
mutants, with a concomitant decrease in motility. Expression of the phospholipase
yplA
was also downregulated in both mutants.
inv
expression was downregulated in
msbB
and
htrB
mutants, and consistent with this finding, invasion of HeLa cells was diminished. However, the expression of
rovA
, the positive regulator of
inv
, was not affected in the mutants. The levels of pYV-encoded virulence factors Yops and YadA in the acyltransferase mutants were not affected. Finally, we show that only the
htrB
mutant was attenuated
in vivo
.
Implementation of SintromacWeb®, a new internet-based tool for oral anticoagulation therapy telecontrol: Study on system consistency and patient satisfaction
Authors: Mira Yolanda , Contreras María Teresa , Aguado Cristina , Aznar José Antonio , Ferrando Fernando 
Published: April 2010

SummaryMost computer- or internet-assisted systems for oral anticoagulation therapy (OAT) telemanagement have limitations when it comes to implementation within a healthcare center. It was the objective of this study to evaluate convenience and patient satisfaction with the use of SintromacWeb→, a new OAT telecontrol system, compared with the conventional control. SintromacWeb® consists of a point-of-care device for patient international normalized ratio (INR) self-testing and software that allows internet mediated interaction with physicians. Patients initiated the use of SintromacWeb→ and were followed up during a three-month period. A score-based questionnaire was completed in three controlled visits, and data were subsequently analysed. A total of 102 patients were enrolled. At first visit, 55.7% of the patients had their INR within normal range, and 64.9% at the final visit. Internal consistency of the questionnaire was good (Cronbach‘s α: 0.79). Scores in the questionnaire were independent of patient’s age, education level, working status and INR value. The most valued features of SintromacWeb® were: fewer visits to the hospital, simplicity and convenience of the system, and time administration for control tasks (86.7%, 82.7% and 77.6% of very satisfied patients, respectively). Also, patients showed indifference or were dissatisfied with the conventional system. At the final visit, 99% of patients declared that they were satisfied with their OAT control. Moreover, all patients continued using Sintrom -acWeb→ after completion of the study. In conclusion, SintromacWeb→ telecontrol is a new model for management of anticoagulated patients. It was highly accepted and can be used by all patients regardless of their sociodemographic characteristics.
The majority of circulating platelet-derived microparticles fail to bind annexin V, lack phospholipid-dependent procoagulant activity and demonstrate greater expression of glycoprotein Ib
Authors: Exner Thomas , Ma David Dang Fung , Joseph Joanne Emily , Connor David Ewan 
Published: April 2010

SummaryIt has been widely accepted that microparticles expose phosphatidylserine which in turn binds annexin V. It was the objective of this study to compare the antigenic characteristics and phospholipid-dependent procoagulant activity of annexin V positive and -negative subpopulations of platelet-derived microparticles. Annexin V positive and -negative microparticles were identified and characterised using flow cytometry and procoagulant activity was measured by a phospholipid-dependent assay (XACT). In unstimulated platelet-poor plasma, 80% of platelet-derived microparticles failed to bind annexin V. Varying the assay constituents (buffer, calcium and annexin V concentration) did not alter annexin V binding. The proportion of microparticles that bound annexin V was dependent upon the agonist, with physiological agonists such as collagen resulting in fewer annexin V binding microparticles than non-physiological agonists such as ionophore. CD42b (glycoprotein Ib) expression was significantly decreased and CD62p and CD63 expression were significantly increased in annexin V positive compared to annexin V negative subpopulations. There was no significant difference in CD41, CD61, CD42a and CD40L expression between annexin V positive and -negative subpopulations. A significant correlation between annexin V binding and XACT was found (p=0.033). Annexin V inhibited greater than 95% of phospholipid activity, suggesting that annexin V binding was a true reflection of procoagulant activity. The majority of platelet-derived microparticles in unstimulated plasma failed to bind annexin V and showed significantly increased levels of CD42b compared to annexin V positive events. Phospholipid-dependent procoagulant activity is limited to the annexin V positive subpopulation and is agonist-dependent. The significance of annexin V negative microparticles is unclear, however, it is possible that they possess other activities aside from procoagulant phospholipid activity.
Thrombophilic risk factors and peripheral arterial disease severity
Authors: Favaretto Elisabetta , Legnani Cristina , Cini Michela , Conti Eleonora , Amato Alfio , Palareti Gualtiero , Sartori Michelangelo 
Published: April 2010

SummaryFew data are available on thrombophilic risk factors and progression of atherosclerotic peripheral arterial disease (PAD). Thrombophilic alterations can be an aggravating factor when arterial stenoses are present. In a cross-sectional study, we evaluated the presence of the thrombophilic factors fibrinogen, homocysteine, factor (F)VIII, lupus anticoagulant (LAC), FII G20210A, and FV R506Q mutations in 181 patients with PAD at Fontaine’s stage II (claudication), in 110 patients with critical limb ischaemia (CLI), and in 210 controls. Fibrinogen was higher in patients with CLI vs. those with claudication and controls (427.9 ± 10.5 vs. 373.1 ± 5.2 vs. 348.9 ± 7.0 p=0.001, respectively). Homocysteine and FVIII were higher in patients with PAD than in controls, but were similar in patients with CLI and claudication. The prevalence of LAC increased in patients with CLI vs. those with claudication and controls (21.4% vs. 7.8% vs. 5.2% p<0.001, respectively). The prevalence of FII 20210A allele was higher in patients with CLI vs. those with claudication and controls. Using a logistic model, FII G20210A mutation (odds ratio [OR] 19.8, confidence interval [CI] 4.5–87.1, p=0.001), LAC (OR 2.7, CI1.1–6.5, p=0.032), and fibrinogen (OR 1.01, CI 1.00–1.01, p=0.001) were associated with CLI, whereas homocysteine, FVIII, and FV R506Q mutation were not. CLI risk increased according to the number of thrombophilic alterations. In conclusion, altered levels of some important thrombophilic risk factors are independently associated with PAD severity. These data suggest that the presence of two or more thrombophilic risk factors raise the likelihood of PAD being more severe, justifying the need for larger longitudinal studies.
Prolonged effect of GlycoPEGylated rFVIIa (40k-PEG-rFVIIa) in rabbits correlates to activity in plasma
Authors: Bjørn Søren E. , Agersø Henrik , Thorup Inger , Hermit Mette B. , Sørensen Brit B. , Stennicke Henning R. , Ezban Mirella , Tranholm Mikael , Johansen Peter B. 
Published: April 2010

SummaryThe pharmacokinetics and pharmacodynamics of 40k-PEG-rFVIIa, a GlycoPEGylated derivative of recombinant wild-type FVIIa, were compared with rFVIIa in rabbits. The procoagulant effect was determined as the weight of the clot formed in a defined segment of a facial vein. A time course study was conducted where ligation was made 10 minutes, 12 or 24 hours after i.v. injection of equimolar doses of 40k-PEG-FVIIa or rFVIIa (2 mg/kg). This dose was selected based on a dose response study and a duration of effect study with rFVIIa. The clot weight increased with increasing doses of rFVIIa, and the duration of effect correlated with the plasma FVIIa clot activity. The plasma half-life of 40k-PEG-rFVIIa measured as FVIIa clot activity was found to be 25 hours, which was 5–6 times longer than rFVIIa. The aPTT and PT were reduced, and the measured increase in thrombin-antithrombin correlated to the effect on clot formation. Thus, the effect was similar at ligation 10 minutes after administration of 40k-PEG-rFVIIa or rFVIIa. At 12 hours, the effect of rFVIIa was absent while significant effect was seen 12 and 24 hours post dosing with 40k-PEG-rFVIIa. No consumption of platelets or fibrinogen was found and no thrombi formation was seen in histological examination of various organs. In conclusion, 40k-PEG-rFVIIa has shown prolonged duration of effect that correlated to various plasma markers and FVIIa clot activity. In perspective, the data support further clinical development of 40k-PEG-rFVIIa to potentially become a long-acting recombinant treatment option for prophylaxis in haemophilia patients with inhibitors.
Islam: the test of globalization
Authors: Char Abdelmajid 
Published: April 2010

Globalization has consequences for the religious sphere, but it does not constitute a break with the previous situation. It constitutes rather an acceleration of a process begun with the birth of nation-states. The impact of the values of modernity is general, since even those in power, whatever their tendency, invoke values of democracy, progress, freedom and justice, whereas submission is what was required of subjects. Nevertheless, people today look to religion for fixed reference points, because of the brutal transition from the Middle Ages to the 20th and 21st centuries, and because modernity is not a endogenous phenomenon. Islam then is playing the role of bulwark against western hegemony. It is also instrumentalized both by the powers that be and by the oppositions, all of whom give themselves over to displays of one-upmanship over fidelity to Islam. Does Islam then maintain its relevance in the context of globalization? The fact is that the bases on which social relations are now founded no longer permit discrimination on the ground of sex or religion, and that there is a loosening of the grip of traditional ritualism and that more and more Muslims are looking for an understanding of the faith that is freed from old-fashioned dogmas. These new givens are being demonstrated particularly when it comes to the exercise of power and the condition of women. As a result, traditional conceptions are destined to evolve, particularly concerning the status of the Koran, the growing awareness of the historical process that made the Koran into a juridical code, the archetype that has been stuck to the person of the Prophet, and the alienation that consists in the sacralization of every human act.
The Clinical Use of Human Culture–Expanded Autologous Bone Marrow Mesenchymal Stem Cells Transplanted on Platelet-Rich Fibrin Glue in the Treatment of Articular Cartilage Defects
Authors: Haleem Amgad M. , Singergy Abdel Aziz El , Sabry Dina , Atta Hazem M. , Rashed Laila A. , Chu Constance R. , Shewy Mohammed T. El , Azzam Akram , Aziz Mohammed T. Abdel 
Published: April 2010

Objective: To test the hypothesis that platelet-rich fibrin glue (PR-FG) can be used clinically as a scaffold to deliver autologous culture-expanded bone marrow mesenchymal stem cells (BM-MSCs) for cartilage repair and to report clinical results 1 y after implantation of MSCs PR-FG. Patients and Methods: Autologous BM-MSCs were culture expanded, placed on PR-FG intraoperatively, and then transplanted into 5 full-thickness cartilage defects of femoral condyles of 5 patients and covered with an autologous periosteal flap. Patients were evaluated clinically at 6 and 12 mo by the Lysholm and Revised Hospital for Special Surgery Knee (RHSSK) scores and radiographically by x-rays and magnetic resonance imaging (MRI) at the same time points. Repair tissue in 2 patients was rated arthroscopically after 12 mo using the International Cartilage Repair Society (ICRS) Arthroscopic Score. Study Design: Case series; level of evidence 4. Results: All patients’ symptoms improved over the follow-up period of 12 mo. Average Lysholm and RHSSK scores for all patients showed statistically significant improvement at 6 and 12 mo postoperatively ( P < 0.05). There was no statistically significant difference between the 6 and 12 mo postoperative clinical scores ( P = 0.18). ICRS arthroscopic scores were 8/12 and 11/12 (nearly normal) for the 2 patients who consented to arthroscopy. MRI of 3 patients at 12 mo postoperatively revealed complete defect fill and complete surface congruity with native cartilage, whereas that of 2 patients showed incomplete congruity. Conclusion: Autologous BM-MSC transplantation on PR-FG as a cell scaffold may be an effective approach to promote the repair of articular cartilage defects of the knee in human patients.
Lentiviral gene therapy of murine hematopoietic stem cells ameliorates the Pompe disease phenotype
Authors: van Til Niek P. , Stok Merel , Aerts Kaya Fatima S. F. , de Waard Monique C. , Farahbakhshian Elnaz , Visser Trudi P. , Kroos Marian A. , Jacobs Edwin H. , Willart Monique A. , van der Wegen Pascal , Scholte Bob J. , Lambrecht Bart N. , Duncker Dirk J. , van der Ploeg Ans T. , Reuser Arnold J. J. , Verstegen Monique M. , Wagemaker Gerard 
Published: April 2010

AbstractPompe disease (acid α-glucosidase deficiency) is a lysosomal glycogen storage disorder characterized in its most severe early-onset form by rapidly progressive muscle weakness and mortality within the first year of life due to cardiac and respiratory failure. Enzyme replacement therapy prolongs the life of affected infants and supports the condition of older children and adults but entails lifelong treatment and can be counteracted by immune responses to the recombinant enzyme. We have explored the potential of lentiviral vector–mediated expression of human acid α-glucosidase in hematopoietic stem cells (HSCs) in a Pompe mouse model. After mild conditioning, transplantation of genetically engineered HSCs resulted in stable chimerism of approximately 35% hematopoietic cells that overexpress acid α-glucosidase and in major clearance of glycogen in heart, diaphragm, spleen, and liver. Cardiac remodeling was reversed, and respiratory function, skeletal muscle strength, and motor performance improved. Overexpression of acid α-glucosidase did not affect overall hematopoietic cell function and led to immune tolerance as shown by challenge with the human recombinant protein. On the basis of the prominent and sustained therapeutic efficacy without adverse events in mice we conclude that ex vivo HSC gene therapy is a treatment option worthwhile to pursue.
Human leukocyte antigen class I and II alleles in non-Hodgkin lymphoma etiology
Authors: Wang Sophia S. , Abdou Amr M. , Morton Lindsay M. , Thomas Rasmi , Cerhan James R. , Gao Xiaojiang , Cozen Wendy , Rothman Nathaniel , Davis Scott , Severson Richard K. , Bernstein Leslie , Hartge Patricia , Carrington Mary 
Published: April 2010

AbstractGenome-wide association and candidate gene studies implicate different genetic variants within the 6p21 chromosomal region with different non-Hodgkin lymphoma (NHL) subtypes. Complementing these efforts, we conducted human leukocyte antigen (HLA) class I and class II genotyping among 610 NHL cases and 555 controls of non-Hispanic white descent from a US multicenter study. Allele-disease associations were assessed by logistic regression for NHL and its subtypes. Statistically significant associations between HLA and NHL subtypes include HLA-DRB1*0101 for follicular lymphoma (odds ratio [OR] = 2.14, P < .001), HLA-DRB1*0401 for diffuse large B-cell lymphoma (DLBCL; OR = 0.45, P = .006), and HLA-DRB1*13 and follicular lymphoma (OR = 0.48, P = .008). We further observed significant heterozygote advantage for HLA class I alleles and NHL, and particularly DLBCL (P trend = .01 for elevated risk with increasing number of homozygous alleles). Our results support a role for HLA in the etiology of NHL and its subtypes.