bluuebunny/crossref_metadata_2025_split huggingface dataset:
Alcohol Consumption and Male Erectile Dysfunction: An Unfounded Reputation for Risk?
Authors: Chew Kew-Kim , Bremner Alexandra , Stuckey Bronwyn , Earle Carolyn , Jamrozik Konrad 
Published: January 2009

ABSTRACT

Introduction
Alcohol consumption is a contentious social topic and is often assumed to have deleterious effects on sexual performance. There is a lack of consensus on whether alcohol consumption may in fact be beneficial to erectile function.

Aim
We examined the data from a population-based cross-sectional study of men’s health to assess the association between usual alcohol consumption and erectile dysfunction (ED).

Method
Reply-paid questionnaires were posted to a randomly selected age-stratified male population sample obtained from the Western Australian (WA) Electoral Roll.

Main Outcome Measures
The survey questionnaire included sociodemographic details, self-reported clinical information, and drinking habits. The 5-item International Index of Erectile Function (IIEF-5) was used to assess erectile function.

Results
Most (87%) participants were current alcohol drinkers, with binge drinking, as defined by the Australian National Health and Medical Research Council (NHMRC), reported by 20% of drinkers. Compared with never-drinkers, the age-adjusted odds of ED were lower among current, weekend, and binge drinkers and higher among ex-drinkers. Among current drinkers, the odds were lowest for consumption within the NHMRC guidelines of between 1 and 20 standard drinks a week. On further adjustment for cardiovascular disease (CVD) or for cigarette smoking, age-adjusted odds of ED were reduced by 25–30% among alcohol drinkers.

Conclusions
Our findings suggest a modest negative association between alcohol consumption and ED and confounding of the association by CVD and cigarette smoking. The Western Australia Men’s Health Study certainly provides no justification for advising men with ED whose drinking habits are consistent with NHMRC guidelines that they should cease or reduce their consumption of alcohol.
Testosterone Replacement Therapy in Naturally and Surgically Menopausal Women (CME)
Authors: Panzer Claudia , Guay André 
Published: January 2009

ABSTRACT

Introduction
Testosterone replacement therapy in naturally and surgically menopausal women is a complex and currently highly debated topic. Opposing guidelines for the use of testosterone exist, which create a therapeutic dilemma for clinicians confronted by severely distressed women who experience a decrease in sexual desire after surgical or natural menopause.

Aim
In this review, we will address the current knowledge on androgen physiology, conditions associated with a low androgen state, and risks and benefits of androgen therapy.

Methods
An English-language Medline review was performed.

Main Outcome Measure
Review of available literature.

Results
A review of normal androgen physiology in women is summarized and a brief review of prior use of androgens over the last six decades is included. The data on the use of androgen replacement in pre- and postmenopausal women is evaluated, especially its relationship to sexual functioning. Special concerns about the effect of androgens on cardiovascular disease, breast, and endometrial tissue are discussed. The balance of evidence seems to show that androgens have more of a positive effect than a negative effect in women if used properly.

Conclusions
Testosterone replacement therapy for surgically and naturally menopausal women with low sexual desire can be accomplished physiologically and effectively after ruling out other medical conditions leading to low sexual desire and after proper information of the patient that testosterone therapy is not an FDA-approved medication in the United States. The majority of available data suggests that testosterone replacement in women can be used safely without increased risk of endometrial or breast cancer.
Aspects of Sexual Satisfaction in Men with Erectile Dysfunction: A Factor Analytic and Logistic Regression Approach
Authors: Fugl-Meyer Axel , Althof Stanley , Buvat Jacques , Paget Marie-Ange , Sotomayor Mariano , Stothard Diane 
Published: January 2009

ABSTRACT

Introduction
The International Index of Erectile Function (IIEF), Sexual Encounter Profile (SEP), and Erectile Dysfunction Inventory of Treatment Satisfaction (EDITS) assess efficacy of phosphodiesterase type 5 (PDE5) inhibitor treatment of erectile dysfunction (ED).

Aims
To determine the degree that multiplicity of satisfaction questions in ED treatment evaluation instruments are congruent, to better understand the concept of sexual “satisfaction,” and to identify factors that correlate with improvement.

Methods
Questionnaire data from 4,174 placebo- or tadalafil-treated patients with ED were analyzed. Principal component analysis (PCA) was performed on IIEF and SEP satisfaction questions. Spearman correlation coefficients were determined. Data from 431 of the 4,174 patients who completed EDITS questionnaires were analyzed. Logistic regression was used to investigate improvement of each IIEF satisfaction question.

Results
PCA rotated on three factors explained 91% of total variance and separated IIEF Q6 (intercourse frequency) from a SEP and a remaining IIEF factor. All correlations between and among questions were close (ρ = 0.62–0.98; P &lt; 0.0001), except for those with IIEF Q6 (ρ = 0.28–0.34; P &lt; 0.0001). In a sub-sample, PCA of five IIEF, two SEP, and three EDITS questions identified four factors that explained 90% of all variance: EDITS questions, IIEF questions except Q6, SEP questions, and IIEF Q6. Greater improvement in IIEF-EF domain score was consistently and positively associated with satisfaction measures (P &lt; 0.0001).

Conclusions
Factor analysis detected close relationships among satisfaction questions in IIEF, SEP, and EDITS instruments, each of which, apart from IIEF Q6 (intercourse frequency), appeared to be an independent measure of satisfaction. Cultural differences may explain different satisfaction correlations with baseline ED severity in different regions. Clinicians may make use of the correlation between intercourse frequency (Q6) and satisfaction when prescribing a PDE5 inhibitor for ED, by explaining that the inhibitor should enable more frequent intercourse.
Comparison of Intracellular Cytokine Flow Cytometry and an Enzyme Immunoassay for Evaluation of Cellular Immune Response to Active Tuberculosis
Authors: Leung Wai Lin , Law Kai Leung , Leung Veronica Sui Shan , Yip Chi Wai , Leung Chi Chiu , Tam Cheuk Ming , Kam Kai Man 
Published: January 2009

ABSTRACT

A prospective cross-sectional blinded study of 28 patients (21 male and 7 female patients; mean age, 44 years) with suspected active tuberculosis (TB) attending a TB and chest clinic is described. Blood was taken for immune cell enumeration, a whole-blood enzyme-linked immunosorbent assay (ELISA) for the detection of gamma interferon (IFN-γ) by the QuantiFERON-TB Gold (QFT-G) assay, and intracellular cytokine flow cytometry (ICC) analysis; and sputum was simultaneously taken for bacteriological culture for
Mycobacterium tuberculosis
. Twelve healthy subjects were included as controls. The performance characteristics of the QFT-G and ICC assays for the detection of active TB were compared. Among the patients with active TB, we found (i) normal to slightly elevated peripheral CD4
+
and CD8
+
T-cell counts but a significant reduction in the number of NK cells; (ii) CD4
+
T cells were the major cell type producing IFN-γ, a type 1 cytokine; (iii) small percentages of CD8
+
T cells were also primed for IFN-γ production; (iv) the production of interleukin-4 (IL-4), a type 2 cytokine, was not prominent; and (v) the sensitivity and the specificity of the QFT-G assay were 88.2% and 18%, respectively, and those of the ICC assay were 94.1% and 36.4%, respectively. The specificities of the blood tests were likely underestimated due to cross-reaction to a non-
M. tuberculosis
mycobacterial infection and the lack of a confirmatory test that could be used to diagnose latent
M. tuberculosis
infection. Flow cytometry accurately locates the pool of immunological effector cells responsible for cytokine production during active TB. The ICC assay is an additional useful tool for the diagnosis of active TB.
Serological Diagnosis of Human Herpes Simplex Virus Type 1 and 2 Infections by Luciferase Immunoprecipitation System Assay
Authors: Burbelo Peter D. , Hoshino Yo , Leahy Hannah , Krogmann Tammy , Hornung Ronald L. , Iadarola Michael J. , Cohen Jeffrey I. 
Published: January 2009

ABSTRACT

Highly quantitative and high-throughput serological tests for evaluation of humoral responses to herpes simplex virus 1 (HSV-1) and HSV-2 are not available. The efficacy of luciferase immunoprecipitation system (LIPS) assays for antibody profiling and serologic diagnosis of HSV-1 and HSV-2 infection was investigated using a panel of five recombinant HSV antigens. Plasma samples from subjects seropositive for HSV-1 and/or HSV-2 or seronegative for HSV-1 and HSV-2 that had previously been analyzed by Western blotting and the Focus Plexus immunoassay were evaluated. The LIPS test measuring anti-gG1 antibody titers was 96% sensitive and 96% specific for detecting HSV-1 infection, compared with the Focus immunoassay, and was 92% sensitive and 96% specific, compared with Western blotting. The results for the anti-gG2 LIPS test for HSV-2 precisely matched those for Western blotting, with 100% sensitivity and 100% specificity, and showed robust antibody titers in all the HSV-2-infected samples that were over 1,000 times higher than those in HSV-2-negative or HSV-1-positive samples. Antibodies to three additional HSV-2 proteins, gB, gD, and ICP8, were detected in many of the HSV-1- and/or HSV-2-infected plasma samples and showed preferentially higher immunoreactivity in HSV-2-infected plasma. The titers of antibodies to these three HSV-2 antigens also significantly correlated with each other (
R
= 0.75 to 0.81;
P
< 0.0001). These studies indicate that the robust anti-gG1 and anti-gG2 antibody responses detected by LIPS assays are useful for HSV-1 and HSV-2 detection and suggest that profiling of antibody responses to a panel of HSV proteins may be useful for characterizing individual humoral responses to infection and for monitoring responses to vaccines.
Simultaneous Detection of
Haemophilus influenzae
Type b Polysaccharide-Specific Antibodies and
Neisseria meningitidis
Serogroup A, C, Y, and W-135 Polysaccharide-Specific Antibodies in a Fluorescent-Bead-Based Multiplex Immunoassay
Authors: de Voer Richarda M. , Schepp Rutger M. , Versteegh Florens G. A. , van der Klis Fiona R. M. , Berbers Guy A. M. 
Published: January 2009

ABSTRACT

We expanded the meningococcal serogroup A, C, Y, and W-135 multiplex immunoassay (MIA) to simultaneously detect immunoglobulin type G antibodies directed toward
Haemophilus influenzae
type b polysaccharide (HibPS). The monoplex HibPS assay was compared to a HibPS-specific competitive enzyme-linked immunosorbent assay and showed a good correlation (
R
= 0.96). Furthermore, no cross-reactivity between HibPS and the four meningococcal serogroups was detected. This pentaplex meningococcal Hib MIA is a useful tool to investigate serological responses toward different childhood PS vaccines.
Generation of Herpesvirus Entry Mediator (HVEM)-Restricted Herpes Simplex Virus Type 1 Mutant Viruses: Resistance of HVEM-Expressing Cells and Identification of Mutations That Rescue Nectin-1 Recognition
Authors: Uchida Hiroaki , Shah Waris A. , Ozuer Ali , Frampton Arthur R. , Goins William F. , Grandi Paola , Cohen Justus B. , Glorioso Joseph C. 
Published: January 2009

ABSTRACT
Both initial infection and cell-to-cell spread by herpes simplex virus type 1 (HSV-1) require the interaction of the viral glycoprotein D (gD) with an entry receptor on the cell surface. The two major HSV entry receptors, herpesvirus entry mediator (HVEM) and nectin-1, mediate infection independently but are coexpressed on a variety of cells. To determine if both receptors are active in these instances, we have established mutant viruses that are selectively impaired for recognition of one or the other receptor. In plaque assays, these viruses showed approximately 1,000-fold selectivity for the matched receptor over the mismatched receptor. Separate assays showed that each virus is impaired for both infection and spread through the mismatched receptor. We tested several human tumor cell lines for susceptibility to these viruses and observed that HT29 colon carcinoma cells are susceptible to infection by nectin-1-restricted virus but are highly resistant to HVEM-restricted virus infection, despite readily detectable HVEM expression on the cell surface. HVEM cDNA isolated from HT29 cells rendered HSV-resistant cells permissive for infection by the HVEM-restricted virus, suggesting that HT29 cells lack a cofactor for HVEM-mediated infection or express an HVEM-specific inhibitory factor. Passaging of HVEM-restricted virus on nectin-1-expressing cells yielded a set of gD missense mutations that each restored functional recognition of nectin-1. These mutations identify residues that likely play a role in shaping the nectin-1 binding site of gD. Our findings illustrate the utility of these receptor-restricted viruses in studying the early events in HSV infection.
P64, a Novel Major Virion DNA-Binding Protein Potentially Involved in Condensing the
Spodoptera frugiperda Ascovirus 1a
Genome
Authors: Tan Yeping , Spears Tatsinda , Bideshi Dennis K. , Johnson Jeffrey J. , Hice Robert , Bigot Yves , Federici Brian A. 
Published: January 2009

ABSTRACT

We recently identified 21 structural proteins in the virion of
Spodoptera frugiperda ascovirus 1a
(SfAV1a), a virus with a large, double-stranded DNA genome of 157 kbp, which attacks species of the lepidopteran family Noctuidae. The two most abundant virion proteins were the major capsid protein and a novel protein (P64) of 64 kDa that contained two distinct domains not known previously to occur together. The amino-terminal half of P64 (residues 1 to 263) contained four repeats (a recently recognized motif with an unknown function) of a virus-specific two-cysteine adaptor. Adjoined to this, the carboxy-terminal half of P64 (residues 279 to 455) contained 14 copies of a highly basic, tandemly repeated motif rich in arginine and serine, having an 11- to 13-amino-acid consensus sequence, SPSQRRSTS(V/K)(A/S)RR, yielding a predicted isoelectric point of 12.2 for this protein. In the present study, we demonstrate by Southwestern analysis that SfAV1a P64 was the only virion structural protein that bound DNA. Additional electrophoretic mobility shift assays showed that P64 bound SfAV1a as well as non-SfAV1a DNA. Furthermore, we show through immunogold labeling of ultrathin sections that P64 is a component of virogenic stroma and appears to be progressively incorporated into the SfAV1a DNA core during virion assembly. As no other virion structural protein bound DNA and no basic DNA-binding proteins of lower mass are encoded by the SfAV1a genome or were identified by proteomic analysis, our results suggest that P64's function is to condense the large genome of this virus and assist in packaging this genome into its virion.
Internal Initiation Stimulates Production of p8 Minicore, a Member of a Newly Discovered Family of Hepatitis C Virus Core Protein Isoforms
Authors: Eng Francis J. , Walewski Jose L. , Klepper Arielle L. , Fishman Sarah L. , Desai Suresh M. , McMullan Laura K. , Evans Matthew J. , Rice Charles M. , Branch Andrea D. 
Published: January 2009

ABSTRACT

The hepatitis C virus (HCV)
core
gene is more conserved at the nucleic acid level than is necessary to preserve the sequence of the core protein, suggesting that it contains information for additional functions. We used a battery of anticore antibodies to test the hypothesis that the
core
gene directs the synthesis of core protein isoforms. Infectious viruses, replicons, and RNA transcripts expressed a p8 minicore containing the C-terminal portion of the p21 core protein and lacking the N-terminal portion. An interferon resistance mutation, U271A, which creates an AUG at codon 91, upregulated p8 expression in Con1 replicons, suggesting that p8 is produced by an internal initiation event and that 91-AUG is the preferred, but not the required, initiation codon. Synthesis of p8 was independent of p21, as shown by the abundant production of p8 from transcripts containing an UAG stop codon that blocked p21 production. Three infectious viruses, JFH-1 (2a
core
), J6/JFH (2a
core
), and H77/JFH (1a
core
), and a bicistronic construct, Bi-H77/JFH, all expressed both p8 and larger isoforms. The family of minicores ranges in size from 8 to 14 kDa. All lack the N-terminal portion of the p21 core. In conclusion, the
core
gene contains an internal signal that stimulates the initiation of protein synthesis at or near codon 91, leading to the production of p8. Infectious viruses of both genotype 1 and 2 HCV express a family of larger isoforms, in addition to p8. Minicores lack significant portions of the RNA binding domain of p21 core. Studies are under way to determine their functions.
An HLA-A2-Restricted T-Cell Epitope Mapped to the BNLF2a Immune Evasion Protein of Epstein-Barr Virus That Inhibits TAP
Authors: Bell Melissa J. , Abbott Rachel J. M. , Croft Nathan P. , Hislop Andrew D. , Burrows Scott R. 
Published: January 2009

ABSTRACTThe early lytic cycle protein of Epstein-Barr virus (EBV), BNLF2a, has recently been shown to play a critical role in immune evasion by inhibiting the peptide transporter associated with antigen processing (TAP), thereby blocking antigen-specific CD8+T-cell recognition of many lytic cycle antigens. Surprisingly, we now show that a peptide (50VLFGLLCLL58) from the hydrophobic C-terminal region of this small (60-amino-acid) EBV protein is efficiently presented by the common class I allele HLA-A2 for recognition by cytotoxic T lymphocytes. The mechanism for this unexpected finding was revealed by experiments showing that this epitope is processed and presented independently of TAP.
Reovirus FAST Protein Transmembrane Domains Function in a Modular, Primary Sequence-Independent Manner To Mediate Cell-Cell Membrane Fusion
Authors: Clancy Eileen K. , Duncan Roy 
Published: January 2009

ABSTRACTThe FAST proteins are a unique family of virus-encoded cell-cell membrane fusion proteins. In the absence of a cleavable N-terminal signal peptide, a single-pass transmembrane domain (TMD) functions as a reverse signal-anchor to direct the FAST proteins into the plasma membrane in an Nexo/Ccyttopology. There is little information available on the role of the FAST protein TMD in the cell-cell membrane fusion reaction. We show that in the absence of conservation in the length or primary amino acid sequence, the p14 TMD can be functionally exchanged with the TMDs of the p10 and p15 FAST proteins. This is not the case for chimeric p14 proteins containing the TMDs of two different enveloped viral fusion proteins or a cellular membrane protein; such chimeric proteins were defective for both pore formation and syncytiogenesis. TMD structural features that are conserved within members of the FAST protein family presumably play direct roles in the fusion reaction. Molecular modeling suggests that the funnel-shaped architecture of the FAST protein TMDs may represent such a conserved structural and functional motif. Interestingly, although heterologous TMDs exert diverse influences on the trafficking of the p14 FAST protein, these TMDs are capable of functioning as reverse signal-anchor sequences to direct p14 into lipid rafts in the correct membrane topology. The FAST protein TMDs are therefore not primary determinants of type III protein topology, but they do play a direct, sequence-independent role in the membrane fusion reaction.
Modified Vaccinia Virus Ankara Triggers Chemotaxis of Monocytes and Early Respiratory Immigration of Leukocytes by Induction of CCL2 Expression
Authors: Lehmann Michael H. , Kastenmuller Wolfgang , Kandemir Judith D. , Brandt Florian , Suezer Yasemin , Sutter Gerd 
Published: January 2009

ABSTRACTOrthopoxviruses commonly enter into humans and animals via the respiratory tract. Herein, we show that immigration of leukocytes into the lung is triggered via intranasal infection of mice with modified vaccinia virus Ankara (MVA) and not with the vaccinia virus (VACV) Elstree, Wyeth, or Western Reserve (WR) strain. Immigrating cells were identified as monocytes, neutrophils, and CD4+lymphocytes by flow cytometry and could be detected 24 h and 48 h postinfection. Using an in vitro chemotaxis assay, we confirmed that infection with MVA induces the expression of a soluble chemotactic factor for monocytes, identified as CCL2 (monocyte chemotactic protein-1 [MCP-1]). In contrast to infection with several other VACV strains, MVA induced the expression of CCL2, CCL3, CCL4, and CXCL10 in the human monocytic cell line THP-1 as well as in primary human monocytes. Thus, MVA, and not the VACV Elstree, Wyeth, or WR strain, consistently triggered the expression of a panel of chemokines, including CCL2, in the murine lung, correlating considerably with the immigration of leukocytes. Using CCL2-deficient mice, we demonstrate that CCL2 plays a key role in MVA-triggered respiratory immigration of leukocytes. Moreover, UV irradiation of MVA prevented CCL2 expression in vitro and in vivo as well as respiratory immigration of leukocytes, demonstrating the requirement for an activated molecular viral life cycle. We propose that MVA-triggered chemokine expression causes early immigration of leukocytes to the site of infection, a feature that is important for rapid immunization and its safety and efficiency as a viral vector.
E4orf1
Limits the Oncolytic Potential of the
E1B
-
55K
Deletion Mutant Adenovirus
Authors: Thomas Michael A. , Broughton Robin S. , Goodrum Felicia D. , Ornelles David A. 
Published: January 2009

ABSTRACT

Clinical trials have shown oncolytic adenoviruses to be tumor selective with minimal toxicity toward normal tissue. The virus ONYX-015, in which the gene encoding the early region 1B 55-kDa (
E1B
-
55K
) protein is deleted, has been most effective when used in combination with either chemotherapy or radiation therapy. Therefore, improving the oncolytic nature of tumor-selective adenoviruses remains an important objective for improving this form of cancer therapy. Cells infected during the G
1
phase of the cell cycle with the
E1B
-
55K
deletion mutant virus exhibit a reduced rate of viral late protein synthesis, produce fewer viral progeny, and are less efficiently killed than cells infected during the S phase. Here we demonstrate that the G
1
restriction imposed on the
E1B
-
55K
deletion mutant virus is due to the viral oncogene encoded by open reading frame 1 of early region 4 (
E4orf1
).
E4orf1
has been reported to signal through the phosphatidylinositol 3′-kinase pathway leading to the activation of Akt, mTOR, and p70 S6K. Evidence presented here shows that
E4orf1
may also induce the phosphorylation of Akt and p70 S6K in a manner that depends on Rac1 and its guanine nucleotide exchange factor Tiam1. Accordingly, agents that have been reported to disrupt the Tiam1-Rac1 interaction or to prevent phosphorylation of the ribosomal S6 kinase partially alleviated the
E4orf1
restriction to late viral protein synthesis and enhanced tumor cell killing by the
E1B
-
55K
mutant virus. These results demonstrate that
E4orf1
limits the oncolytic nature of a conditionally replicating adenovirus such as ONYX-015. The therapeutic value of similar oncolytic adenoviruses may be improved by abrogating
E4orf1
function.