bluuebunny/crossref_metadata_2025_split huggingface dataset:
B Cell Infection and Activation by Rabies Virus-Based Vaccines
Authors: Lytle Andrew G. , Norton James E. , Dorfmeier Corin L. , Shen Shixue , McGettigan James P. 
Published: June 2013

ABSTRACTReplication-deficient rabies viruses (RABV) are promising rabies postexposure vaccines due to their prompt and potent stimulation of protective virus neutralizing antibody titers, which are produced in mice by both T-dependent and T-independent mechanisms. To promote such early and robust B cell stimulation, we hypothesized that live RABV-based vaccines directly infect B cells, thereby activating a large pool of antigen-presenting cells (APCs) capable of providing early priming and costimulation to CD4+T cells. In this report, we show that live RABV-based vaccine vectors efficiently infect naive primary murine and human B cellsex vivo. Infection of B cells resulted in the significant upregulation of early markers of B cell activation and antigen presentation, including CD69, major histocompatibility complex class II (MHC-II), and CD40 in murine B cells or HLA-DR and CD40 in human B cells compared to mock-infected cells or cells treated with an inactivated RABV-based vaccine. Furthermore, primary B cells infected with a live RABV expressing ovalbumin were able to prime and stimulate naive CD4+OT-II T cells to proliferate and to secrete interleukin-2 (IL-2), demonstrating a functional consequence of B cell infection and activation by live RABV-based vaccine vectors. We propose that this direct B cell stimulation by live RABV-based vaccines is a potential mechanism underlying their induction of early protective T cell-dependent B cell responses, and that designing live RABV-based vaccines to infect and activate B cells represents a promising strategy to develop a single-dose postexposure rabies vaccine where the generation of early protective antibody titers is critical.
Merkel Cell Polyomavirus Large T Antigen Disrupts Host Genomic Integrity and Inhibits Cellular Proliferation
Authors: Li Jing , Wang Xin , Diaz Jason , Tsang Sabrina H. , Buck Christopher B. , You Jianxin 
Published: June 2013

ABSTRACT
Clonal integration of Merkel cell polyomavirus (MCV) DNA into the host genome has been observed in at least 80% of Merkel cell carcinoma (MCC). The integrated viral genome typically carries mutations that truncate the C-terminal DNA binding and helicase domains of the MCV large T antigen (LT), suggesting a selective pressure to remove this MCV LT region during tumor development. In this study, we show that MCV infection leads to the activation of host DNA damage responses (DDR). This activity was mapped to the C-terminal helicase-containing region of the MCV LT. The MCV LT-activated DNA damage kinases, in turn, led to enhanced p53 phosphorylation, upregulation of p53 downstream target genes, and cell cycle arrest. Compared to the N-terminal MCV LT fragment that is usually preserved in mutants isolated from MCC tumors, full-length MCV LT shows a decreased potential to support cellular proliferation, focus formation, and anchorage-independent cell growth. These apparently antitumorigenic effects can be reversed by a dominant-negative p53 inhibitor. Our results demonstrate that MCV LT-induced DDR activates p53 pathway, leading to the inhibition of cellular proliferation. This study reveals a key difference between MCV LT and simian vacuolating virus 40 LT, which activates a DDR but inhibits p53 function. This study also explains, in part, why truncation mutations that remove the MCV LT C-terminal region are necessary for the oncogenic progression of MCV-associated cancers.
Utility of the Pentax-AWS in performing tracheal intubation while wearing chemical, biological, radiation and nuclear personal protective equipment: a randomised crossover trial using a manikin
Authors: Shin Dong Hyuk , Choi Pil Cho , Na Ji Ung , Cho Jun Hwi , Han Sang Kuk 
Published: June 2013

IntroductionFollowing a chemical, biological, radiation and nuclear (CBRN) incident, prompt establishment of an advanced airway is required for patients with respiratory failure within the warm zone, while wearing personal protective equipment (PPE). Previous studies reported that intubation attempts were prolonged, and incidence of esophageal intubation was increased with conventional Macintosh laryngoscope (McL), while wearing CBRN-PPE. Pentax-AWS (AWS), a recently introduced portable video laryngoscope, was compared with the McL to test its utility for tracheal intubation while wearing CBRN-PPE.Methods31 participants performed unsuited and suited intubations on an advanced life support simulator. The sequence of intubating devices and PPE wearing were randomised. Time to complete tracheal intubation (primary end point), time to see the vocal cords, overall success rate, percentage of glottic opening, dental compression and ease of intubation were measured.ResultsSuited intubations required significantly longer time to complete intubation than unsuited intubations, in both McL and AWS (22.2 vs 26.4 s, 14.2 vs 18.2 s, respectively). However, suited AWS intubations required shorter time to complete tracheal intubation than unsuited McL intubations (18.2 vs 22.2 s). In secondary outcomes, moreover, suited intubations using the AWS compared favourably with unsuited intubations using the McL.ConclusionsAlthough the CBRN-PPE adversely affected time required to complete tracheal intubation with the AWS, suited intubations using the AWS were even superior to unsuited intubations using the McL. The AWS should be a promising device to perform tracheal intubation while wearing the CBRN-PPE.
BARRIERS AND BENEFITS TO LEARNING IN NATURAL ENVIRONMENTS: TOWARDS A RECONCEPTUALISATION OF THE POSSIBILITIES FOR CHANGE
Authors: DILLON JUSTIN 
Published: June 2013

Policies designed to increase public engagement with biodiversity advocate increased education across a range of educational contexts. Evidence of the benefits of learning in natural environments (LINE) continues to be amassed. LINE affords direct benefits as diverse as educational, health and psychological and indirect benefits ranging from social to financial. Research into the value of LINE has failed to address the full range of benefits. Instead, there has been a narrow focus on easily measurable outcomes and a desire to seek answers to simplistic questions such as "does LINE raise standards more than learning in the classroom?" An attempt is made to outline the full range of benefits which are available to all school students. The outcomes include: benefits to individual participants (knowledge and understanding; skills; attitudes and behaviours; health and well-being; self-efficacy and self-worth); benefits to teachers, schools and the wider community, and benefits to the natural environment sector.Several barriers exist to the effective delivery of LINE. These barriers can be grouped into those that challenge the natural environment sector and those that challenge schools. The challenges facing the sector include a lack of a coordinated effective approach to working with schools at a local level. The challenges facing schools include those frequently mentioned such as the risk of accidents, cost and curriculum pressures. However, another set of challenges exists, at local, institutional and personal levels. These challenges include teachers' confidence, self-efficacy and their access to training in using natural environments close to the school and further afield.
Soluble Inter‐Cellular Adhesion Molecule‐1 in Urban Asian North Indians: Relationships with Anthropometric and Metabolic Covariates
Authors: Sethi Astha , Misra Anoop , Pandey Ravindra Mohan , Luthra Kalpana , Devi J. Rama , Sharma Rekha , Khanna Nidhi , Dwivedi Manjari , Vikram Naval Kishore 
Published: June 2013

Background: High prevalence of diabetes, obesity, and dyslipidemias in people belonging to poor socio‐economic strata in urban slums of northern India has been recorded recently. To assess whether this population has high levels of soluble intercellular adhesion molecule‐1 (sICAM‐1), a cytokine involved in the pathogenesis of atherosclerosis, we investigated subjects belonging to poor socio‐economic strata in urban slums and compared them to healthy control subjects from non‐slum urban areas of New Delhi.Design: Cross‐sectional study.Methods: Subjects from a previously carried out cross‐sectional study, Delhi Urban Slum Project (DUSP) were divided into two groups: Group‐1 (n = 56) included subjects dwelling in slum area, having at least one risk factor (hypertension, hyperglycemia, hypertriglyceridemia and hypercholesterolemia), while group‐2 (n = 60) consisted of subjects without any risk factor dwelling in the slum area. A third group (n = 29) of non‐obese subjects without any risk factor living in non‐slum urban area was included for comparison. Measurements included; body mass index (BMI), waist‐hip ratio (W‐HR), four skinfolds, percentage body fat, fasting plasma glucose (FPG), serum lipids, and serum levels of sICAM‐1.Results: Though statistically not significant, mean level of sICAM‐1 was higher in group‐1 (718.5 ± 232.8 ng/ml) as compared to the other groups. Of note, 35% of subjects in group‐1 (p < 0.05 as compared to other two groups), and 25.3% of all subjects had levels of sICAM‐1 in uppermost quartile (>850 ng/ml). Partial correlation coefficients (R) of sICAM‐1 levels with various parameters adjusted for age were statistically significant for BMI (R = 0.27, p < 0.05) in group‐1; W‐HR (R = 0.26, p < 0.05) and BMI (R = 0.19, p < 0.05) for group‐2; and FPG (R = 0.17, p < 0.05) for all the subjects considered together. For females, the levels of sICAM‐1 were significantly higher in the following: BMI ≥ 25 kg/m2 (p = 0.04) and FPG >7 mmol/l (p < 0.05). Multiple linear regression analysis suggests that an increment in BMI by one kg/m2 would correspond to an increase in the levels of sICAM‐1 by 8.5 units controlling for the influence of age and W‐HR in the pooled data of all subjects.Conclusions: High percentage of subjects had levels of sICAM‐1 in the upper quartile in the study, particularly those dwelling in the slum area and having coronary risk factor (s). The levels of sICAM‐1 strongly correlated to the anthropometric and metabolic parameters, particularly in females. These observations are of potential importance for the pathogenesis of atherosclerosis in this population, though further studies are needed to predict those prone to the complications of atherosclerosis, based on sICAM‐1 levels, as has been observed in other ethnic groups.
GSTT1 Gene Deletion Is Associated with Lung Cancer in Mexican Patients
Authors: Gallegos-Arreola M. P. , Gómez-Meda B. C. , Morgan-Villela G. , Arechavaleta-Granell M. R. , Arnaud-López L. , Beltrán-Jaramillo T. J. , Gaxiola R. , Zúñiga-González G. 
Published: June 2013

Glutathione S‐transferase (GST) is a dimeric detoxifying isoenzyme, involved in the deactivation of carcinogens, several tobacco‐derived carcinogens, and xenobiotics. It catalyzes the reduction of glutathione to its thioester; thus, deficiency in GST activity due to homozygous deletion of the GSTT1 gene (null genotype) may play a role in the induction of lung cancer by smoking.We studied the distribution of GSTT1 gene deletion in peripheral blood DNA samples from 178 healthy controls (41 nonsmokers, 63 passive smokers and 74 smokers) and 52 lung cancer patients. Comparisons between groups showed that there was an increased lung cancer risk for individuals with the GSTT1 null genotype. Cancer patients showed significant differences when compared with controls: nonsmokers, passive smokers, and smokers. Twenty‐one percent of lung cancer patients carried the deletion versus 2% among nonsmokers not exposed to passive smoking, 6% among passive smokers, and 5% among smokers. Thus, there is a significant association between this genotype and the possibility to risk of developing lung cancer.
CYP1A1 Genetic Polymorphisms in Ecuador, South America
Authors: Paz-y-Miño César , Arévalo Melissa , Muñoz G. María José , Leone Paola. E. 
Published: June 2013

A total of 108 individuals from the Ecuadorian population from rural and urban places were analyzed for two CYP1A1 gene polymorphisms. The frequency of the val allele at codon 462 was 0.50, while the frequency of the Msp I restriction site, m2 allele at the T6235C position was 0.70. These polymorphisms in Ecuador have higher frequencies if we compare with others around the world, with the exception of some South American population in Brazil and Chile.Erratum to “CYP1A1 Genetic Polymorphisms in Ecuador, South America” dx.doi.org/10.1155/2005/231396
Age‐Dependent Decrease in Serum Transforming Growth Factor (TGF)‐Beta 1 in Healthy Japanese Individuals; Population Study of Serum TGF‐Beta 1 Level in Japanese
Authors: Okamoto Yoshihiro , Gotoh Yoshimitsu , Uemura Osamu , Tanaka Soichi , Ando Tsunesaburo , Nishida Mikio 
Published: June 2013

Transforming growth factor‐beta1 (TGF‐β1), a multi‐functional cytokine, is involved in regulating a variety of cellular activities and the serum/plasma TGF‐β1 level is altered with various diseases. However, most published reports have described adult patients, and so we investigated the clinical significance of serum TGF‐β1 level in pediatric patients. The diagnostic application of the measurement of serum TGF‐β1 level depends critically on the control value, however, there is no information on the control value of serum TGF‐β1 for children.In the present study, we determined the serum TGF‐β1 level of healthy Japanese children as a control value with enzyme‐linked immunosorbent assay (ELISA). The serum TGF‐β1 level of children (0–14 years old) was significantly higher than that of adults (over 15 years old) (p < 0.01). Thus, it is recommended that when the serum TGF‐β1 levels of patients are evaluated, they should be compared with those of age‐matched controls.
Complete Mutation Screening and Haplotype Characterization of the BRCA1 Gene in 61 Familial Breast Cancer Patients from Norway
Authors: Frost Petter , Jugessur Astanand , Apold Jaran , Heimdal Ketil , Aloysius Thomas , Eliassen Aud K. , Fauske Lars , Matre Guri , Eiken Hans Geir 
Published: June 2013

Mutations in the Breast-Cancer-1 (BRCA1) gene are the major cause of familial breast/ovarian cancer. Among familial breast cancer only, 15–20% have been suggested to have a deleterious mutation in BRCA1. A highly sensitive method (REF‐SSCP) was applied to screen the open reading frame and the 5’UTRs of BRCA1 for mutations. The patient cohort comprised 61 unrelated moderate to high risk breast cancer patients from Western‐Norway.Only one known deleterious BRCA1 mutation (c.816‐817delGT) was found in two of the 61 patients (3.3%). Four haplotypes were established based on nine known single nucleotide polymorphisms. Two patients had a novel deletion (c.‐33_‐29delAAAAA) in the 5’UTR, and a novel amino acid substitution (L523W) was found in one patient. Size variations analysis in the 5’UTR was repeated in a cohort of 159 unrelated familial breast/ovarian cancer patients and 94 healthy blood donors. Two patients were identified with 5’UTR (c.‐30 to ‐60) variations (CAAAA)5 and (CAAAA)7, instead of the (CAAAA)6‐repeat. All of the identified 5’UTR size variations were localized between the start codon and the most stable secondary structures previously proposed for the exon 1b transcript. No such alterations were found among the healthy blood donors but association studies of the 5′UTR variations within the respective families were not conclusive.
Serum Levels of Platelet Released CD40 Ligand Are Increased in Early Onset Occlusive Carotid Artery Disease
Authors: Balla József , Magyar Mária Tünde , Bereczki Dániel , Valikovics Attila , Nagy Emöke , Barna Erika , Pál András , Balla György , Csiba László , Blaskó György 
Published: June 2013

Objective: Soluble CD40 ligand (sCD40L) has been suggested as a key mediator between inflammation and atherosclerosis, and the CD40‐CD40L interaction has a role in atherosclerotic lesion progression. We evaluated if platelet released serum sCD40L and sCD40 levels differ between patients with early onset occlusive carotid artery disease and age‐matched controls.Methods: sCD40L and sCD40 levels were measured in serum samples of 60 patients with occlusive carotid artery disease and 30 age‐matched controls using ELISA. Degree of stenosis of the internal carotid artery (ICA), and intima‐media thickness (IMT) in the common carotid artery were measured by high resolution ultrasound. Values are given as mean ± SD.Results: Mean age was 50.9 ± 3.5 and 50.1 ± 3.5 years in the patient and control groups. IMT was significantly thicker in patients than in controls (0.89 ± 0.14 vs. 0.78 ±0.12 mm, p = 0.0003). Serum levels of sCD40L were significantly higher (6.9 ± 5 vs. 4.5 ± 3.0 ng/mL, p = 0.038) in patients, whereas sCD40 did not differ significantly between patients and controls (85 ± 56.9 vs. 79.3 ± 18.7 pg/mL, p = 0.34). IMT did not correlate with sCD40L or sCD40 levels (R = −0.03, p = 0.77; and R = 0.109, p = 0.308, respectively).Conclusions: sCD40L but not sCD40 levels are significantly higher in patients with occlusive carotid artery disease. Platelet derived sCD40L may be a key mediator among inflammation, thrombosis and atherosclerosis.
Glycosylation Changes on Serum Glycoproteins in Ovarian Cancer May Contribute to Disease Pathogenesis
Authors: Saldova Radka , Wormald Mark R. , Dwek Raymond A. , Rudd Pauline M. 
Published: June 2013

Ovarian cancer is the most lethal of all gynaecological cancers among women. Serum CA125 is the only biomarker that is used routinely and there is a need for further complementary biomarkers both in terms of sensitivity and specificity.N‐glycosylation changes in ovarian cancer serum glycoproteins include a decrease in galactosylation of IgG and an increase in sialyl Lewis X (SLex) on haptoglobin β‐chain, α1‐acid glycoprotein and α1‐antichymotrypsin. These changes are also present in chronic inflammation but not in malignant melanoma, where there are low levels of inflammatory processes. Acute phase proteins carrying increased amounts of SLex have an increased half‐life. Sialylation of acute phase proteins also decreases apoptosis favouring survival of cancer cells. Cancer cells produce inflammatory cytokines which influence glycosylation processing in liver parenchymal cells. Altered glycosylation of the acute phase protein transferrin plays an important role in iron homeostasis. Glycosylated transferrin and its glycans have anti‐apoptotic properties and many transferrin receptors in carcinoma could play a role in development of anaemia. Decreased galactosylation and sialylation of IgG increases the cytotoxicity of natural killer cells and complement activation via mannose‐binding lectin (MBL). Altered glycosylation of acute phase proteins and IgG suggests that cancer regulates certain pathways favouring cancer cells survival.
Human Neutrophil Peptides 1‐3 – Early Markers in Development of Colorectal Adenomas and Carcinomas
Authors: Mothes Henning , Melle Christian , Ernst Günther , Kaufmann Roland , von Eggeling Ferdinand , Settmacher Utz 
Published: June 2013

Expression of Human Neutrophil Peptides (HNP) 1–3 was recently found to be associated with development of colorectal cancer. Raised defensin‐expression in tumours is believed to stem from increased infiltration of neutrophils into tumour environment.To further specify the role of α‐defensins in tumourigenesis and progression, HNP1–3 were analyzed in colorectal adenomas and carcinomas of 87 patients and quantified in relation to cancer stage and grading. Using the ProteinChip arrays, HNP1–3 were found upregulated in both colorectal adenomas and carcinomas. By combining the array with Laser capture microscopy we were able to confirm that HNP1–3 are expressed by tumour cells but not by neutrophils or other tumour invading cells. These findings suggest that α‐defensins are more likely to contribute to tumour growth than they are to mount an effective host anti‐tumour response. However, the amount of HNP‐expression was not found to be related to tumour stage, grading, and serological tumour markers.
Circulating VEGF As a Biological Marker in Patients with Rheumatoid Arthritis? Preanalytical and Biological Variability in Healthy Persons and in Patients
Authors: Hetland Merete Lund , Christensen Ib Jarle , Lottenburger Tine , Johansen Julia Sidenius , Svendsen Mads Nordahl , Hørslev-Petersen Kim , Nielsen Lone , Jørgen Nielsen Hans 
Published: June 2013

Background: Soluble vascular endothelial growth factor (VEGF) is a promising biomarker in monitoring rheumatoid arthritis (RA), but studies of pre‐analytical and biologic variability are few.Methods: VEGF was measured by ELISA methods in serum and plasma from healthy persons and RA patients. Pre‐analytical factors were investigated. A reference interval for VEGF was established in serum and plasma from 306 healthy persons. Diurnal, day‐to‐day, week‐to‐week, long‐term variability, and impact of exercise were evaluated.Results: Delayed processing time, room temperature, low centrifugal force and contamination of plasma with cellular elements lead to significant increases in VEGF levels, whereas storage for up to 2 years at −80°C or up to 10 freeze/thaw cycles did not affect VEGF levels. Serum VEGF levels were 7–10 fold higher than plasma VEGF levels. Reference intervals for VEGF (plasma: 45 pg/ml (range: non‐detectable to 352); serum: 328 pg/ml (53–1791)) were independent of gender and age. Short‐ and long‐term biologic variability included diurnal variation (sampling should take place after 7 AM) and impact of exercise (increased VEGF immediately after bicycling normalised within 1 hour).Conclusions: Pre‐analytical factors and biologic variability including diurnal variation and impact of exercise should be accounted for in future studies that include circulating VEGF as a biological marker.
Protective Effect of R Allele of PON1 Gene on the Coronary Artery Disease in the Presence of Specific Genetic Background
Authors: Balcerzyk Anna , Zak Iwona , Krauze Jolanta 
Published: June 2013

Background: Genetic susceptibility to CAD may be determined by polymorphic variants of genes encoding isoforms involved in the processes important in the pathogenesis of atherosclerosis, including lipids disorders. Participation of single polymorphic variants is relatively small, however its significance may increase in the presence of specific genetic or environmental background.Aim: The aim of the study was an evaluation a possible association between single polymorphic variants of PON1, APOE, ABCA1 and PPARA genes and CAD and looking for specific multigene genotype patterns which differentiate study groups.Materials and methods: We studied 358 subjects:178 patients with angiographically confirmed CAD and 180 blood donors without history of CAD. Polymorphisms were genotyped using PCR‐RFLP method.Results: We observed statistically significant differences in the frequencies of R allele and R allele carriers of PON1 gene between CAD and controls. The distribution of genotypes and alleles of other analyzed genes did not differentiate the study groups, however the presence of specific genotypes (APOE– ɛ3ɛ3, ɛ3ɛ2, ABCA1 – AG, PPARA – GG) increased the protective effect of R allele.Conclusion: The present study revealed an independent protective association between carrier‐state of PON1 R allele and CAD. This protective effect was especially strong in the presence of specific genotype arrangements of other analyzed genes.