bluuebunny/crossref_metadata_2025_split huggingface dataset:
Reinvestigating the Role of IgM in Rabies Virus Postexposure Vaccination
Authors: Dorfmeier Corin L. , Shen Shixue , Tzvetkov Evgeni P. , McGettigan James P. 
Published: June 2013

ABSTRACTB cells secreting IgG antibodies, but not IgM, are thought to be solely responsible for vaccine-induced protection against rabies virus (RABV) infections in postexposure settings. In this report, we reinvestigated the potential for IgM to mediate protection in a mouse model of RABV vaccination. Immunocompetent mice immunized with an experimental live replication-deficient RABV-based vaccine produced virus neutralizing antibodies (VNAs) within 3 days of vaccination. However, mice unable to produce soluble IgM (sIgM−/−) did not produce VNAs until 7 days postimmunization. Furthermore, sIgM−/−mice were not protected against RABV infection when challenged 3 days postimmunization, while all wild-type mice survived challenge. Consistent with the lack of protection against pathogenic RABV challenge, approximately 50- to 100-fold higher viral loads of challenge virus were detected in the muscle, spinal cord, and brain of immunized sIgM−/−mice compared to control mice. In addition, IgG antibody titers in vaccinated wild-type and sIgM−/−mice were similar at all time points postimmunization, suggesting that protection against RABV challenge is due to the direct effects of IgM and not the influence of IgM on the development of effective IgG antibody titers. In all, early vaccine-induced IgM can limit dissemination of pathogenic RABV to the central nervous system and mediate protection against pathogenic RABV challenge. Considering the importance for the rapid induction of VNAs to protect against RABV infections in postexposure prophylaxis settings, these findings may help guide the development of a single-dose human rabies vaccine.
Characterization of a Critical Interaction between the Coronavirus Nucleocapsid Protein and Nonstructural Protein 3 of the Viral Replicase-Transcriptase Complex
Authors: Hurst Kelley R. , Koetzner Cheri A. , Masters Paul S. 
Published: June 2013

ABSTRACTThe coronavirus nucleocapsid protein (N) plays an essential structural role in virions through a network of interactions with positive-strand viral genomic RNA, the envelope membrane protein (M), and other N molecules. Additionally, N protein participates in at least one stage of the complex mechanism of coronavirus RNA synthesis. We previously uncovered an unanticipated interaction between N and the largest subunit of the viral replicase-transcriptase complex, nonstructural protein 3 (nsp3). This was found through analysis of revertants of a severely defective mutant of murine hepatitis virus (MHV) in which the N gene was replaced with that of its close relative, bovine coronavirus (BCoV). In the work reported here, we constructed BCoV chimeras and other mutants of MHV nsp3 and obtained complementary genetic evidence for its association with N protein. We found that the N-nsp3 interaction maps to the amino-terminal ubiquitin-like domain of nsp3, which is essential for the virus. The interaction does not require the adjacent acidic domain of nsp3, which is dispensable. In addition, we demonstrated a complete correspondence between N-nsp3 genetic interactions and the ability of N protein to enhance the infectivity of transfected coronavirus genomic RNA. The latter function of N was shown to depend on both of the RNA-binding domains of N, as well as on the serine- and arginine-rich central region of N, which binds nsp3. Our results support a model in which the N-nsp3 interaction serves to tether the genome to the newly translated replicase-transcriptase complex at a very early stage of infection.
A pilot study of an Enhanced Mental Health Assessment during routine and discharge medicals in the British Armed Forces
Authors: Aguirre Marcela , Greenberg N , Sharpley J , Simpson R , Wall C 
Published: June 2013

ObjectivesA pilot study to assess the practicality of introducing an enhanced mental health assessment (EMHA) into all routine and discharge medicals of the UK Armed Forces in order to facilitate treatment prior to and on return to civilian life.MethodsA pilot study was conducted using an EMHA questionnaire with questions about depression, anxiety, post-traumatic stress disorder, alcohol use, sleep and anger/irritability. At pilot sites, the EMHA was completed during all routine and discharge medicals between May 2011 and July 2011. At the end of the study period, qualitative data were collected from participating medical officers and practice managers regarding their opinions about the pilot study.ResultsThe quantitative data revealed an average pick-up rate for mental health (MH) problems. Out of the four military medical centres who participated and the 325 questionnaires collected, one referral to a Department of Community Mental Health was made. 26 (8%) patients were categorised as ‘some concern and patient offered advice and/or reassurance’. The vast majority of patients were found to have no evidence of MH problems. However, using a validated alcohol screening tool, 64% of service personnel were found to have a score indicating ‘higher risk drinking’. Analysis of the qualitative data suggests that the EMHA is an easy tool to implement with minimal additional time and resources needed. The interviewees pointed out a number of limitations and suggestions for possible further studies.ConclusionsThe pilot study successfully demonstrated that the EMHA questionnaire is easy to administer, does not take up a large amount of additional resources or manpower and provides a useful check of MH status. The study picked up an average number of MH cases and the questions on alcohol consumption highlighted that military personnel may be at a ‘higher risk of drinking’.
Mechanical Spectral Signatures of Malignant Disease? A Small‐Sample, Comparative Study of Continuum vs. Nano‐Biomechanical Data Analyses
Authors: Liu Jun , Ferrari Mauro 
Published: June 2013

Thin sections from human breast biopsies were employed to perform a differential analysis of the ultrasound spectral responses from invasive ductal carcinoma and normal tissue. A non‐destructive testing methodology was employed, yielding the reflection coefficients as function of frequency in the clinical ultrasound range. The spectral responses were simulated both in the context of continuum and nano‐biomechanics, with the objective of quantifying the physical properties that determine the differences in the spectral signature of normal vs. malignant tissue. The properties that were employed for the theoretical reconstruction of the spectra were: the density, the continuum and the nanomechanical elastic constants, and the nanomechanical theory internodal distance. The latter is a measure of the depth‐of‐penetration of mechanical actions between contiguous tissue elements. Together with vectorial descriptors of the tissue spatial arrangement, the internodal distance variable affords the quantitative incorporation of tissue architectural data in the theoretical model.In this paper, the validity of the nanomechanical approach to tissue characterization is discussed, and its potential extensions to biomolecular marker‐based cancer diagnostics and therapeutics are considered.
Endostatin Polymorphism 4349G/A(D104N) is not Associated with Aggressiveness of Disease in Postate Cancer
Authors: Li He Cheng , Cai Qiu Yin , Shinohara Eric T. , Cai Hui , Cao Carolyn , Fei Wang Zuo , Teng Ming , Zheng Wei , Lu Bo 
Published: June 2013

Endostatin is an important inhibitory molecule which mediates the sequential steps involved in angiogenesis. Lower level or impaired function of endostatin is associated with a higher risk of developing malignant solid tumors and with a worse prognosis of the disease. The endostatin N104 polymorphism might be associated with an impaired ability to inhibit angiogenesis. We analyzed the tissues from 98 Caucasian prostate cancer patients for the presence of D104N polymorphism. The frequencies of homozygous 4349G/G(104D/D), and heterozygous 4349G/A(104D/N) were 83.67%(82/98) and 16.33%(16/98), respectively; no individuals were homozygous 4349A/A(104N/N). With the Fisher’s exact test we found the genotype of D104N was not significantly related to age, tumor grade, PSA and clinical stage (P > 0.05). There was no difference in relapse free survival(RFS) or overall survival(OS) between patients with 104D/N and those with 104D/D (P = 0.8283, 0.3713 respectively). We concluded that endostatin polymorphism was not associated with the aggressiveness of prostate cancer in Caucasian patients.Erratum of “Endostatin Polymorphism 4349G/A(D104N) Is Not Associated with Aggressiveness of Disease in Postate Cancer” dx.doi.org/10.1155/2005/318394
TLR‐4 and CD14 Polymorphisms in Respiratory Syncytial Virus Associated Disease
Authors: Puthothu Beena , Forster Johannes , Heinzmann Andrea , Krueger Marcus 
Published: June 2013

Respiratory syncytial virus (RSV) is the most common viral respiratory pathogen during infancy world wide. It induces innate and adaptive immune response in host cells. The toll like receptor 4 (TLR4)/CD14 complex is particularly important for the initiation of an innate immune response to RSV. Thus we were interested whether an association exists between severe RSV associated diseases and polymorphisms within TLR4 and CD14.We genotyped the CD14 promotor polymorphism ‐C159T and the two common TLR4 amino acid variants (D259G, and T359I) in 131 infants with severe RSV associated diseases and 270 controls. Statistical analyses of single polymorphisms made use of the Armitage’s trend test, haplotypes were calculated by FAMHAP, FASTEHPLUS and Arlequin.All polymorphisms were in Hardy Weinberg Equilibrium. We found marginal association between amino acid exchange D259G in TLR4 with RSV infection p = 0.0545). Furthermore, haplotypes analysis of the two TLR4 polymorphisms by three independent programs revealed association of haplotypes with severe RSV infection (p ≤ 0.0010). In contrast, the promotor polymorphism within CD14 was not associated with susceptibility to RSV disease. We conclude from our study, that TLR4 polymorphisms, and particularly the haplotypes, may influence the genetic predisposition to severe RSV infection.
Apolipoprotein E in Temporal Lobe Epilepsy: A Case‐Control Study
Authors: Kumar Amit , Tripathi Manjari , Pandey Ravindra M. , Ramakrishnan Lakshmy , Srinivas M. , Luthra Kalpana 
Published: June 2013

Purpose: To investigate the relationship of apolipoprotein E (apoE) genotype, plasma levels of apoE and lipids in temporal lobe epilepsy (TLE) patients in Asian Indians. Status of plasma levels of Apo E in epilepsy patients has not been reported till date.Methods: ApoE gene polymorphism was analyzed in 58 patients with temporal lobe epilepsy (TLE) and 57 age and sex approximated controls using Polymerase chain reaction‐ restriction fragment length polymorphism (PCR‐RFLP). Levels of plasma apoE and lipids were measured using ELISA and enzymatic kits respectively.Results: The distribution of ApoE genotype in epilepsy patients and controls was comparable. Higher levels of plasma ApoE were observed in TLE patients as compared to controls (p = 0.0001). Individuals with plasma levels of apoE > 190 mg/L were at 20 times higher odds (95%CI = 2.46–163.34, p = 0.005), while those with levels of apoE between 150–190 mg/L were at 4.9 times higher odds (95% CI = 1.85–13.9, p = 0.001), to develop TLE.Conclusions: We have observed for the first time, high levels of plasma apoE in epilepsy patients. The findings of this case‐control study suggest that apolipoprotein E may play an important role in epilepsy.
Matrix Metalloproteinase Expression Patterns in Luminal A Type Breast Carcinomas
Authors: Decock J. , Hendrickx W. , Drijkoningen M. , Wildiers H. , Neven P. , Smeets A. , Paridaens R. 
Published: June 2013

Objective: Aberrant expression of individual matrix metalloproteinases has been associated with poor prognosis in various human carcinomas. The current study aimed at defining an RNA expression profile of various MMPs in breast cancer and correlating their expression with clinicopathological parameters.Methods: The RNA expression patterns of 6 MMPs (MMP2, MMP8, MMP9, MMP10, MMP11, MMP13) were determined in 25 breast carcinomas using quantitative RT‐PCR and correlated with clinicopathological parameters, including menopausal status, tumor size and grade, and lymph node involvement.Results: We observed high MMP2 levels more frequently in premenopausal than in postmenopausal women (p = 0.02). Analysis of luminal A type invasive ductal carcinomas (19/25), revealed an even stronger association of MMP2 with menopausal status (p = 0.005). Within this subgroup, we also found a correlation between MMP11 and menopausal status (p = 0.02). No correlation was found between MMP expressions and other clinicopathological parameters. In co‐expression analyses MMP2‐MMP10 and MMP8‐MMP9 showed a weak correlation of their expression.Conclusions: Although this is a pilot study, our findings indicate that luminal A invasive ductal carcinomas commonly express high MMP2 and MMP11 levels in premenopausal breast cancer patients and suggest a co‐regulation of MMP2‐MMP10 and MMP8‐MMP9.
Overexpression of Fascin‐1 in Advanced Colorectal Adenocarcinoma: Tissue Microarray Analysis of Immunostaining Scores with Clinicopathological Parameters
Authors: Tsai Wen-Chiuan , Chao You-Chen , Sheu Lai-Fa , Chang Junn-Liang , Nieh Shin , Jin Jong-Shiaw 
Published: June 2013

Objective: Fascin‐1 is an actin‐binding protein that promotes cell proliferation, adhesion and motility. We tested the hypothesis that fascin‐1 expression correlates with clinicopathological parameters of colorectal adenocarcinomas.Methods: Immunohistochemical analysis of fascin‐1 was performed in tissue microarrays of 91 surgical specimens, including 32 well, 33 moderately, and 26 poorly differentiated colorectal adenocarcinomas; and in 22 specimens from colorectal adenomas with dysplasia.Results: Scattered fascin‐1 expression was demonstrated in 9 control specimens of normal colonic glandular epithelia. Higher fascin‐1 immunostaining scores were significantly associated with advanced dysplasia in colorectal adenomas (mild 4.2 ± 1.3, moderate 13.5 ± 5.3, and severe 22.5 ± 6.7) and high‐grade histopathological differentiation of colorectal adenocarcinomas (grade I 88.6 ± 9, grade II 101 ± 11, and grade III 144 ± 13). Higher immunostaining scores of fascin‐1 were also significantly associated with advanced T stage (T1: 42 ± 10, T2: 60 ± 12, T3: 108 ± 12, and T4: 142 ± 15). Higher fascin‐1 scores were related with more advanced M and N stages of colorectal carcinomas, but not significant correlation.Conclusions: Higher expression of fascin‐1 correlates significantly with tumor grades and TNM stages in colorectal adenocarcinomas and also with levels of dysplastic change in colorectal adenomas.
Low Plasma Levels of FGF‐2 and PDGF‐BB Are Associated with Cardiovascular Events in Type II Diabetes Mellitus (Diabetes Heart Study)
Authors: Yeboah Joseph , Sane David C. , Crouse John R. , Herrington David M. , Bowden Donald W. 
Published: June 2013

Objective: We tested associations of the growth factors VEGF, FGF‐2, HGF and PDGF‐BB with coronary artery calcium scores and cardiovascular events (CVD) in type 2 diabetes mellitus (T2DM).Methods: A cross‐sectional study selected 40 frequency matched (by age, gender and race) subjects with T2DM from the first (0–111) and the third (> 1400) coronary artery calcium (CAC) score tertiles in the Diabetes Heart Study (DHS), in which 36 were with and 41 were without history of CVD events. Plasma levels of VEGF, FGF‐2, HGF and PDGF‐BB were measured in all subjects.Results: None of the growth factors was significantly different between the first and third CAC score tertiles. Mean plasma FGF‐2 and PDGF‐BB levels were significantly higher in the group without prior CVD events compared with the group with prior CVD events [mean(95%CI): 219.20 (194.42–247.15) vs. 152.93 (135.64–172.43) pg/ml, p = 0.03] and [mean(95%CI): 106.70 (89.12–127.74) vs. 61.56 (50.91–74.44) pg/ml, p = 0.03], respectively. Subgroup analysis in the first CAC tertile showed a significantly higher PDGF‐BB levels in those without compared with those with CVD events [mean (95%CI): 208.36 (190.57–228.15) vs. 102.93 (80.64–125.21) pg/ml, p = 0.004].Conclusion: Plasma growth factor levels were not significantly different between the extremes of CAC scores in T2DM. However, low plasma levels of PDGF‐BB and FGF‐2 are associated with prior cardiovascular events in T2DM. Studies are needed to confirm our results and also to establish temporality of this association.
Analysis of Crohn’s Disease‐Related CARD15 Polymorphisms in Spanish Patients with Idiopathic Uveitis
Authors: Rodríguez-Pérez N. , Aguinaga-Barrilero A. , Gorroño-Echebarría Marina B. , Pérez-Blas Mercedes , Martín-Villa J. M. 
Published: June 2013

We wished to analyse the frequency of Crohn’s disease‐linked CARD15 polymorphisms (P268S, R702W, G908R and 1007fs) in a group of Spanish patients with idiopathic uveitis. To this aim, DNA samples were obtained from 111 unrelated patients. P268S, R702W and G908R polymorphisms were detected using TaqMan Genotyping kits (Applied Biosystems), and the 1007fs variation by direct DNA sequencing. Control group consisted of 105 healthy subjects.None of the polymorphisms studied revealed a significant increase in the groups of patients, when compared to the control group. Thus, P268S is found in 50% of patients (gene frequency 0.284) vs 44% of control individuals (gene frequency 0.245); R702W in 7% of patients (0.036) vs 7% (0.033); G908R in 2% of patients (0.009) vs 4% (0.019) and, finally, 1007fs in 2% of uveitis patients (0.008) vs 4% (0.021). Moreover, DNA sequencing has allowed us to define two new intronic polymorphisms in phase, in the 5′ and 3′ boundaries of the exon 11 (GenBank accession number #DQ 869189).Altogether, our results suggest that the Crohn’s disease‐linked CARD15 polymorphisms do not seem to predispose to idiopathic uveitis in the Spanish population.
Erythrocyte Aggregation As an Early Biomarker in Patients with Asymptomatic Carotid Stenosis
Authors: Assayag Einor Ben , Bova Irena , Kesler Anat , Berliner Shlomo , Shapira Itzhak , Bornstein Natan M. 
Published: June 2013

Background: Atherosclerosis is a chronic inflammatory disease.Design: We have evaluated the degree of erythrocyte aggregation (EA) as a microinflammatory biomarker in a cohort of hospital‐based, neurologically asymptomatic outpatients.Methods: The degree of EA and carotid artery stenosis was evaluated in 510 individuals by using a simple slide test and image analysis.Results: Four hundred and sixteen individuals had minimal carotid stenosis (< 30%); 47 had mild to moderate stenosis (30–69%)
and 47 had severe stenosis (>70%). A significant correlation was noted between the degree of carotid stenosis and the erythrocyte sedimentation rate (ESR), white blood cell count (WBCC) and fibrinogen (r=0.160, p=0.005;r=0.191, p=0.001 andr=0.126, p=0.026, respectively). The significant correlation was noted between the degree of carotid stenosis and EA (r=0.209, p < 0.001). The subjects with severe stenosis differed significantly from the other groups in their ESR, WBCC and EA.
High sensitivity C‐reactive protein (hs‐CRP) concentrations did not discriminate between the presence and absence of significant
carotid atherosclerotic disease.Conclusions: Inflammatory biomarkers such as ESR and the EA test are more sensitive than hs‐CRP to the presence of a significant atherosclerotic carotid burden. These biomarkers might aid in the detection and quantification of microinflammation in individuals with carotid atherosclerosis.
Association of Interleukin‐10 Gene Promoter Polymorphisms in Saudi Patients with Vitiligo
Authors: Abanmi Abdullah , Al Harthi Fahad , Zouman Abdulrahman , Kudwah Aida , Jamal Mohammed Al , Arfin Misbahul , Tariq Mohammad 
Published: June 2013

The promoter region of human Interleukin −10 gene is highly polymorphic and has been associated with numerous autoimmune diseases. Recent studies have linked vitiligo with defective autoimmune system. This study is aimed to explore a possible association between IL‐10 gene polymorphism and vitiligo in Saudi population. This case control study consisted of 184 Saudi subjects including 83 vitiligo patients (40 males, 43 females mean age 27.85 ± 12.43 years) and 101 matched controls. Genomic DNA was extracted from the blood samples of healthy controls and Vitiligo patients visiting out patient clinic of Department of Dermatology, Riyadh Armed Forces Hospital, using QIA ampR DNA mini kit (Qiagen CA, USA). Interleukin‐10 gene was amplified by polymerase chain reaction (PCR) using Arms primers to detect any polymorphism involved at positions −592, −819 and −1082.The frequencies of GG genotype at −1082, and CC genotype at positions −592 and 819 were significantly higher in vitiligo patients compared to healthy subjects suggesting that GG and CC genotypes might be susceptible to vitiligo in Saudis. On the other hand genotypes −1082 GA, −819 CT, and −592 CA of IL‐10 were more prevalent in healthy controls suggesting protective effects of GA, CT and CA genotypes against vitiligo. This study indicates that the IL‐10 gene may play a significant role in the etiology of vitiligo among Saudis.
The oxidation ratio of LDL: A Predictor for Coronary Artery Disease
Authors: Huang Huiling , Mai Weiyi , Liu Dan , Hao Yuantao , Tao Jun , Dong Yugang 
Published: June 2013

Objective: Oxidized LDL cholesterol (ox‐LDL‐C) is considered to be a key factor of initiating and accelerating atherosclerosis (AS). The purpose of this study is to elucidate the sensitivity and specificity of ox‐LDL and oxidation ratio of LDL in the diagnosis of coronary artery disease (CAD). For the first time, we investigated the ratio of ox‐LDL to ALB(ox‐LDL/ALB).Methods and results: Blood ox‐LDL, total cholesterol (TC), high density lipoprotein cholesterol (HDL‐C), low density lipoprotein cholesterol (LDL‐C), triglyceride (TG) and albumin (ALB) were measured in patients with acute myocardial infarction (AMI, n = 80), unstable angina pectoris (UAP, n = 80), stable angina pectoris (SAP, n = 80), normal control (n = 60), and dyslipidemia control (n = 60). Ox‐LDL was measured by competitive ELISA. The level of ox‐LDL and oxidation ratio of LDL(ox‐LDL/TC, ox‐LDL/HDL‐C, ox‐LDL/ LDL‐C and ox‐LDL/ALB) were significantly higher in each diseased group than controls (P < 0.001). In CAD group, ox‐LDL and oxidation ratio of LDL in subjects complicated with hypertension (HT) and/or diabetes mellitus (DM) increased further (P < 0.001). Ox‐LDL/ALB in the AMI group was 7 times higher than normal control group (0.068 ± 0.017 vs 0.009 ± 0.007, P < 0.001). The area under the curve (AUC) of receiver operating characteristic curve (ROC curve) is a criterium to evaluate the accuracy of diagnosing a disease. The AUC of ROC curve of ox‐LDL/TC, ox‐LDL/HDL‐C, ox‐LDL, ox‐LDL/ALB and ox‐LDL/ LDL‐C for diagnosing CAD were 0.975, 0.975, 0.966, 0.966, 0.957 respectively (P < 0.001). When ox‐LDL/TC = 0.175, the sensitivity and specificity of diagnosing CAD were 0.917 and 0.925, which were almost equal to each other, indicating that the rates of missed diagnosis and misdiagnosis for CAD were the lowest.Conclusions: The level of ox‐LDL and the ratio of ox‐LDL/TC, ox‐LDL/LDL‐C, ox‐LDL/HDL‐C and ox‐LDL/ALB are better biomarkers than TC, TG, HDL‐C and LDL‐C for discriminating between patients with coronary artery disease and healthy subjects. And patients who have a high ratio of ox‐LDL /TC may have a higher risk for CAD.