bluuebunny/crossref_metadata_2025_split huggingface dataset:
Analyzing Location‐Based Accessibility to Dental Services: An Ohio Case Study
Authors: Horner Mark W. , Mascarenhas Ana Karina 
Published: May 2007

AbstractOral health is important to overall health. Therefore, dental services should be available and accessible in order for patients to receive care.Objective: This study aims to identify regional inequities in dental provider location and suggest an innovative methodology that could be useful in establishing new dental facilities that are geographically accessible.Methods: Using a census of dentist locations for the state of Ohio in 1998, geographical accessibility to dental care was analyzed. A geographic information systems (GIS)‐based model to evaluate the regional distribution of dentists was developed. In this article, it is applied to estimate the number of new dental facilities needed based on the geographical proximity or distance to nearest dentist or dental facility. Results are interactively displayed and mapped with GIS for visualization.Results: Four hundred thirteen of 1,008 zip codes in Ohio did not have dentists. Using a service standard of S=5 (all zip codes without dentists must be within 5 miles of a zip code with a dentist), 307 zip codes were not served by dentists. With a standard of S=10, only 45 zip codes in Ohio were not served by dentists, with only 24 additional offices needed to be located to allow accessibility to a dentist within 10 miles.Conclusions: Using GIS and geographical techniques to reveal and solve the potential locational inequities in accessibility to dental care, this work links oral health policy with geographical techniques.
Functional and Specific Antibody Responses in Adult Volunteers in New Zealand Who Were Given One of Two Different Meningococcal Serogroup B Outer Membrane Vesicle Vaccines
Authors: Wedege E. , Bolstad K. , Aase A. , Herstad T. K. , McCallum L. , Rosenqvist E. , Oster P. , Martin D. 
Published: May 2007

ABSTRACT

This study presents detailed analyses of total and specific serum antibody levels among 26 and 24 adult volunteers before vaccination and after the third dose of the meningococcal serogroup B outer membrane vesicle (OMV) vaccines MeNZB and MenBvac, respectively, in a clinical trial in New Zealand (V. Thornton, D. Lennon, K. Rasanathan, J. O'Hallahan, P. Oster, J. Stewart, S. Tilman, I. Aaberge, B. Feiring, H. Nokleby, E. Rosenqvist, K. White, S. Reid, K. Mulholland, M. J. Wakefield, and D. Martin, Vaccine 24:1395-1400, 2006). With the homologous vaccine strains as targets, both vaccines induced significant increases in serum bactericidal and opsonophagocytic activities and in the levels of immunoglobulin G (IgG) to OMV antigens in an enzyme-linked immunosorbent assay (ELISA) and to live meningococci by flow cytometry. They also induced high levels of activity against the heterologous strains, particularly in terms of opsonophagocytic activity and IgG binding to live bacteria. The antibody levels with the homologous and heterologous strains in the four assays showed high and significant positive correlations. Specific IgG binding to 10 major OMV antigens in each vaccine was measured by scanning of immunoblots; ELISAs for two antigens, lipopolysaccharide and
Neisseria
surface protein A (NspA), were also performed. Both vaccines elicited significant increases in IgG binding to all homologous and heterologous OMV antigens except NspA. The total IgG band intensity on the blots correlated significantly with the IgG levels determined by the OMV ELISA and flow cytometry. In conclusion, the results of the various immunological assays showed that both OMV vaccines gave rise to high levels of specific and cross-reacting antibodies.
Lipopolysaccharide Analogs Improve Efficacy of Acellular Pertussis Vaccine and Reduce Type I Hypersensitivity in Mice
Authors: Geurtsen Jeroen , Banus H. Alexander , Gremmer Eric R. , Ferguson Henke , de la Fonteyne-Blankestijn Liset J. J. , Vermeulen Jolanda P. , Dormans Jan A. M. A. , Tommassen Jan , van der Ley Peter , Mooi Frits R. , Vandebriel Rob J. 
Published: May 2007

ABSTRACT

Pertussis is an infectious disease of the respiratory tract that is caused by the gram-negative bacterium
Bordetella pertussis
. Although acellular pertussis (aP) vaccines are safe, they are not fully effective and thus require improvement. In contrast to whole-cell pertussis (wP) vaccines, aP vaccines do not contain lipopolysaccharide (LPS). Monophosphoryl lipid A (MPL) and
Neisseria meningitidis
LpxL2 LPS have been shown to display immune-stimulating activity while exerting little endotoxin activity. Therefore, we evaluated whether these LPS analogs could increase the efficacy of the aP vaccine. Mice were vaccinated with diphtheria-tetanus-aP vaccine with aluminum, MPL, or LpxL2 LPS adjuvant before intranasal challenge with
B. pertussis
. Compared to vaccination with the aluminum adjuvant, vaccination with either LPS analog resulted in lower colonization and a higher pertussis toxin-specific serum immunoglobulin G level, indicating increased efficacy. Vaccination with either LPS analog resulted in reduced lung eosinophilia, reduced eosinophil numbers in the bronchoalveolar lavage fluid, and the ex vivo production of interleukin-4 (IL-4) by bronchial lymph node cells and IL-5 by spleen cells, suggesting reduced type I hypersensitivity. Vaccination with either LPS analog increased serum IL-6 levels, although these levels remained well below the level induced by wP, suggesting that supplementation with LPS analogs may induce some reactogenicity but reactogenicity considerably less than that induced by the wP vaccine. In conclusion, these results indicate that supplementation with LPS analogs forms a promising strategy that can be used to improve aP vaccines.
Use of CultureSwab Plus Swabs with Amies Gel Agar for Testing of Naris Specimens with the GeneOhm MRSA Assay
Authors: Bourbeau P. P. , Riley J. A. , Shoemaker B. C. , Jones K. S. 
Published: May 2007

ABSTRACT

The GeneOhm MRSA assay detects nasal colonization with methicillin-resistant
Staphylococcus aureus
(MRSA). We compared the use of seeded swabs with liquid Stuart's medium and that of seeded swabs with Amies gel for the assay. Overall, the swabs with liquid Stuart's medium detected significantly greater numbers of MRSA than the swabs with Amies gel (
P
= 0.0003).
Comparison of the Digene Hybrid Capture 2 Assay and Roche AMPLICOR and LINEAR ARRAY Human Papillomavirus (HPV) Tests in Detecting High-Risk HPV Genotypes in Specimens from Women with Previous Abnormal Pap Smear Results
Authors: Stevens Matthew P. , Garland Suzanne M. , Rudland Elice , Tan Jeffrey , Quinn Michael A. , Tabrizi Sepehr N. 
Published: May 2007

ABSTRACT

The development of cervical cancer is strongly associated with the presence of persistent high-risk (HR) human papillomavirus (HPV) infection. Recently, the commercially manufactured PCR-based Roche AMPLICOR (AMP) and LINEAR ARRAY (LA) HPV tests have become available for HPV detection. However, knowledge of their clinical performance compared to the U.S. Food and Drug Administration-approved Hybrid Capture 2 (HC2) assay is limited. This study evaluated the concordance between the HC2, AMP, and LA tests in detecting HR-HPV among a cohort of 1,679 women with previous abnormal Pap smear results. Overall, 1,393 specimens (81.3%) generated concordant results for HR-HPV presence or absence by the three assays. The concordance levels were substantial between the HC2 and AMP tests (84.4%, κ = 0.6419) and between the HC2 and LA tests (84.0%, κ = 0.6341) and nearly perfect between the AMP and LA tests (97.8%, κ = 0.9441). HR-HPV prevalence, as detected by the AMP or LA tests, was significantly higher among women with cytological or histological high-grade disease (CIN2 or greater) than that detected by HC2 (
P
< 0.0001). The AMP and LA tests exhibited greater sensitivity, but lower specificity, than HC2 for detecting HR-HPV among this cohort of women with underlying cervical abnormalities, particularly among subjects with histologically proven high-grade disease. Both PCR-based HPV tests may be valuable in the management of care for women with underlying cervical abnormalities, in predicting treatment success, and in studying the clearance or acquisition of new infections.
Protracted Course of Lymphocytic Choriomeningitis Virus WE Infection in Early Life: Induction but Limited Expansion of CD8+Effector T Cells and Absence of Memory CD8+T Cells
Authors: Belnoue Elodie , Fontannaz-Bozzotti Paola , Grillet Stéphane , Lambert Paul-Henri , Siegrist Claire-Anne 
Published: May 2007

ABSTRACTViral infections in human infants frequently follow a protracted course, with higher viral loads and delayed viral clearance compared to viral infections in older children. To identify the mechanisms responsible for this protracted pattern of infection, we developed an infant infection murine model using the well-characterized lymphocytic choriomeningitis virus (LCMV) WE strain in 2-week-old BALB/c mice. In contrast to adult mice, in which viral clearance occurred as expected 8 days after infection, LCMV titers persisted for several weeks after infection of infant mice. LCMV-specific effector CD8+T cells were elicited in infant mice and fully functional on day 7 but rapidly waned and could not be recovered from day 12 onwards. We show here that this results from the failure of LCMV-specific CD8+T cells to expand and the absence of protective LCMV-specific memory CD8+T cells. Under these early life conditions, viral control and clearance are eventually achieved only through LCMV-specific B cells that contribute to protect infant mice from early death or chronic infection.
Investigation of Adenovirus Occurrence in Pediatric Tumor Entities
Authors: Kosulin Karin , Haberler Christine , Hainfellner Johannes A. , Amann Gabriele , Lang Susanna , Lion Thomas 
Published: May 2007

ABSTRACTAdenoviruses (AdVs) contain genes coding for proteins with transforming potential, and certain AdV serotypes have been shown to induce tumors in rodents. However, data on the possible oncogenicity of AdVs in humans are scarce. We have therefore employed a real-time quantitative PCR (RQ-PCR) assay permitting highly sensitive detection of all 51 currently known human AdV serotypes to screen more than 500 tumor specimens derived from 17 different childhood cancer entities including leukemias, lymphomas, and solid tumors. Most tumor entities analyzed showed no evidence for the presence of AdV sequences, but AdV DNA was detected by RQ-PCR in different brain tumors including 25/30 glioblastomas, 22/30 oligodendrogliomas, and 20/30 ependymomas. Nonmalignant counterparts of AdV-positive brain tumors, including specimens of ependymal cells, plexus choroideus, and periventricular white matter, were screened for control purposes and revealed the presence of AdV DNA in most specimens tested. Identification of the AdV types present in positive malignant and nonmalignant brain tissue specimens revealed predominantly representatives of species B and D and, less commonly, C. To exclude contamination as a possible cause of false-positive results, specimens with AdV sequences detectable by PCR were subsequently analyzed by in situ hybridization, which confirmed the PCR findings in all instances. The central nervous system appears to represent a common site of AdV infection with virus persistence, thus providing the first evidence for the possible contribution of AdVs to the multistep process of tumor pathogenesis in brain tissue.
Analysis of Ribavirin Mutagenicity in Human Hepatitis C Virus Infection
Authors: Chevaliez Stéphane , Brillet Rozenn , Lázaro Ester , Hézode Christophe , Pawlotsky Jean-Michel 
Published: May 2007

ABSTRACTThe addition of ribavirin to alpha interferon therapy significantly increases response rates for patients with chronic hepatitis C virus (HCV) infection, but ribavirin's antiviral mechanisms are unknown. Ribavirin has been suggested to have mutagenic potential in vitro that would lead to “error catastrophe,” i.e., the generation of nonviable viral quasispecies due to the increment in the number of mutant genomes, which prevents the transmission of meaningful genetic information. We used extensive sequence-based analysis of two independent genomic regions in order to test in vivo the hypothesis that ribavirin administration accelerates the accumulation of mutations in the viral genome and that this acceleration occurs only when HCV replication is profoundly inhibited by coadministered alpha interferon. The rate of variation of the consensus sequence, the frequency of mutation, the error generation rate, and the between-sample genetic distance were measured for patients receiving ribavirin monotherapy, a combination of alpha interferon three times per week plus ribavirin, or a combination of alpha interferon daily plus ribavirin. Ribavirin monotherapy did not increase the rate of variation of the consensus sequence, the mutation frequency, the error generation rate, or the between-sample genetic distance. The accumulation of nucleotide substitutions did not accelerate, relative to the pretreatment period, during combination therapy with ribavirin and alpha interferon, even when viral replication was profoundly inhibited by alpha interferon. This study strongly undermines the hypothesis whereby ribavirin acts as an HCV mutagen in vivo.
CD163 Expression Confers Susceptibility to Porcine Reproductive and Respiratory Syndrome Viruses
Authors: Calvert Jay G. , Slade David E. , Shields Shelly L. , Jolie Rika , Mannan Ramasamy M. , Ankenbauer Robert G. , Welch Siao-Kun W. 
Published: May 2007

ABSTRACT

Direct functional screening of a cDNA expression library derived from primary porcine alveolar macrophages (PAM) revealed that CD163 is capable of conferring a porcine reproductive and respiratory syndrome virus (PRRSV)-permissive phenotype when introduced into nonpermissive cells. Transient-transfection experiments showed that full-length CD163 cDNAs from PAM, human U937 cells (histiocytic lymphoma), African green monkey kidney cells (MARC-145 and Vero), primary mouse peritoneal macrophages, and canine DH82 (histocytosis) cells encode functional virus receptors. In contrast, CD163 splice variants without the C-terminal transmembrane anchor domain do not provide PRRSV receptor function. We established several stable cell lines expressing CD163 cDNAs from pig, human, and monkey, using porcine kidney (PK 032495), feline kidney (NLFK), or baby hamster kidney (BHK-21) as the parental cell lines. These stable cell lines were susceptible to PRRSV infection and yielded high titers of progeny virus. Cell lines were phenotypically stable over 80 cell passages, and PRRSV could be serially passed at least 60 times, yielding in excess of 10
5
50% tissue culture infective doses/ml.
Induction of MxA Gene Expression by Influenza A Virus Requires Type I or Type III Interferon Signaling
Authors: Holzinger Dirk , Jorns Carl , Stertz Silke , Boisson-Dupuis Stéphanie , Thimme Robert , Weidmann Manfred , Casanova Jean-Laurent , Haller Otto , Kochs Georg 
Published: May 2007

ABSTRACTThe human MxA gene belongs to the class of interferon (IFN)-stimulated genes (ISGs) involved in antiviral resistance against influenza viruses. Here, we studied the requirements for MxA induction by influenza A virus infection. MxA is transcriptionally upregulated by type I (alpha and beta) and type III (lambda) IFNs. Therefore, MxA is widely used in gene expression studies as a reliable marker for IFN bioactivity. It is not known, however, whether viruses can directly activate MxA expression in the absence of secreted IFN. By using an NS1-deficient influenza A virus and human cells with defects in IFN production or the STAT1 gene, we studied the induction profile of MxA by real-time reverse transcriptase PCR. The NS1-deficient virus is known to be a strong activator of the IFN system because NS1 acts as a viral IFN-antagonistic protein. Nevertheless, MxA gene expression was not inducible by this virus upon infection of IFN nonproducer cells and STAT1-null cells. Likewise, neither IFN-α nor IFN-λ had a sizeable effect on the STAT1-null cells, indicating that MxA expression requires STAT1 signaling and cannot be triggered directly by virus infection. In contrast, the expression of the IFN-stimulated gene ISG56 was induced by influenza virus in these cells, confirming that ISG56 differs from MxA in being directly inducible by viral triggers in an IFN-independent way. In summary, our study reveals that MxA is a unique marker for the detection of type I and type III IFN activity during virus infections and IFN therapy.
Recognition of a Defined Region within p24 Gag by CD8+T Cells during Primary Human Immunodeficiency Virus Type 1 Infection in Individuals Expressing Protective HLA Class I Alleles
Authors: Streeck Hendrik , Lichterfeld Mathias , Alter Galit , Meier Angela , Teigen Nickolas , Yassine-Diab Bader , Sidhu Harlyn K. , Little Susan , Kelleher Anthony , Routy Jean-Pierre , Rosenberg Eric S. , Sekaly Rafick-Pierre , Walker Bruce D. , Altfeld Marcus 
Published: May 2007

ABSTRACTHuman immunodeficiency virus type 1 (HIV-1)-specific immune responses during primary HIV-1 infection appear to play a critical role in determining the ultimate speed of disease progression, but little is known about the specificity of the initial HIV-1-specific CD8+T-cell responses in individuals expressing protective HLA class I alleles. Here we compared HIV-1-specific T-cell responses between subjects expressing the protective allele HLA-B27 or -B57 and subjects expressing nonprotective HLA alleles using a cohort of over 290 subjects identified during primary HIV-1 infection. CD8+T cells of individuals expressing HLA-B27 or -B57 targeted a defined region within HIV-1 p24 Gag (amino acids 240 to 272) early in infection, and responses against this region contributed over 35% to the total HIV-1-specific T-cell responses in these individuals. In contrast, this region was rarely recognized in individuals expressing HLA-B35, an HLA allele associated with rapid disease progression, or in subjects expressing neither HLA-B57/B27 nor HLA-B35 (P< 0.0001). The identification of this highly conserved region in p24 Gag targeted in primary infection specifically in individuals expressing HLA class I alleles associated with slower HIV-1 disease progression provides a rationale for vaccine design aimed at inducing responses to this region restricted by other, more common HLA class I alleles.
Peptide-Mediated Interference with Influenza A Virus Polymerase
Authors: Ghanem Alexander , Mayer Daniel , Chase Geoffrey , Tegge Werner , Frank Ronald , Kochs Georg , García-Sastre Adolfo , Schwemmle Martin 
Published: May 2007

ABSTRACT
The assembly of the polymerase complex of influenza A virus from the three viral polymerase subunits PB1, PB2, and PA is required for viral RNA synthesis. We show that peptides which specifically bind to the protein-protein interaction domains in the subunits responsible for complex formation interfere with polymerase complex assembly and inhibit viral replication. Specifically, we provide evidence that a 25-amino-acid peptide corresponding to the PA-binding domain of PB1 blocks the polymerase activity of influenza A virus and inhibits viral spread. Targeting polymerase subunit interactions therefore provides a novel strategy to develop antiviral compounds against influenza A virus or other viruses.
Truncated Form of the Epstein-Barr Virus Protein EBNA-LP Protects against Caspase-Dependent Apoptosis by Inhibiting Protein Phosphatase 2A
Authors: Garibal Julie , Hollville Émilie , Bell Andrew I. , Kelly Gemma L. , Renouf Benjamin , Kawaguchi Yasushi , Rickinson Alan B. , Wiels Joëlle 
Published: May 2007

ABSTRACT
The Epstein-Barr virus (EBV)-encoded leader protein, EBNA-LP, strongly activates the EBNA2-mediated transcriptional activation of cellular and viral genes and is therefore important for EBV-induced B-cell transformation. However, a truncated form of EBNA-LP is produced in cells infected with variant EBV strains lacking EBNA2 due to a genetic deletion. The function of this truncated form is unknown. We show here that some Burkitt's lymphoma cells harboring defective EBV strains are specifically resistant to the caspase-dependent apoptosis induced by verotoxin 1 (VT-1) or staurosporine. These cells produced low-molecular-weight Y1Y2-truncated isoforms of EBNA-LP, which were partly localized in the cytoplasm. The transfection of sensitive cells with constructs encoding truncated EBNA-LP isoforms, but not full-length EBNA-LP, induced resistance to caspase-mediated apoptosis. Furthermore, VT-1 induced protein phosphatase 2A (PP2A) activation in sensitive cells but not in resistant cells, in which the truncated EBNA-LP interacted with this protein. Thus, the resistance to apoptosis observed in cells harboring defective EBV strains most probably results from the inactivation of PP2A via interactions with low-molecular-weight Y1Y2-truncated EBNA-LP isoforms.
Function of the Respiratory Syncytial Virus Small Hydrophobic Protein
Authors: Fuentes Sandra , Tran Kim C. , Luthra Priya , Teng Michael N. , He Biao 
Published: May 2007

ABSTRACT

Respiratory syncytial virus (RSV), a member of the
Paramyxoviridae
family, encodes a small hydrophobic (SH) protein of unknown function. Parainfluenza virus 5 (PIV5), a prototypical paramyxovirus, also encodes an SH protein, which inhibits tumor necrosis factor alpha (TNF-α) signaling. In this study, recombinant PIV5 viruses without their own SH but containing RSV SH (from RSV strain A2 or B1) in its place (PIV5ΔSH-RSV SH) and RSV lacking its own SH (RSVΔSH) were generated and analyzed. The results indicate that the SH protein of RSV has a function similar to that of PIV5 SH and that it can inhibit TNF-α signaling.
Small Interfering RNA Profiling Reveals Key Role of Clathrin-Mediated Endocytosis and Early Endosome Formation for Infection by Respiratory Syncytial Virus
Authors: Kolokoltsov Andrey A. , Deniger Drew , Fleming Elisa H. , Roberts Norbert J. , Karpilow Jon M. , Davey Robert A. 
Published: May 2007

ABSTRACT
Respiratory syncytial virus (RSV) is a common cause of respiratory tract infections in infants and the elderly. Like many other pH-independent enveloped viruses, RSV is thought to enter at the cell surface, independently of common endocytic pathways. We have used a targeted small interfering RNA (siRNA) library to identify key cellular genes involved in cytoskeletal dynamics and endosome trafficking that are important for RSV infection. Surprisingly, RSV infection was potently inhibited by siRNAs targeting genes associated with clathrin-mediated endocytosis, including clathrin light chain. The important role of clathrin-mediated endocytosis was confirmed by the expression of well-characterized dominant-negative mutants of genes in this pathway and by using the clathrin endocytosis inhibitor chlorpromazine. We conclude that, while RSV may be competent to enter at the cell surface, clathrin function and endocytosis are a necessary and important part of a productive RSV infection, even though infection is strictly independent of pH. These findings raise the possibility that other pH-independent viruses may share a similar dependence on endocytosis for infection and provide a new potential avenue for treatment of infection.