bluuebunny/crossref_metadata_2025_split huggingface dataset:
Interleukin-15 Increases Vaccine Efficacy through a Mechanism Linked to Dendritic Cell Maturation and Enhanced Antibody Titers
Authors: Saikh Kamal U. , Kissner Teri L. , Nystrom Steven , Ruthel Gordon , Ulrich Robert G. 
Published: November 2007

ABSTRACTInterleukin-15 (IL-15) is generally considered to sustain T-cell memory and to be a growth factor for natural killer cells. Previous data from our laboratory demonstrated that IL-15 is also an important factor for developing human dendritic cells. For this study, we investigated the effects of IL-15 on antibody responses in mice to a recombinant staphylococcal enterotoxin B (SEB) vaccine (STEBVax) in a preclinical model of toxic shock syndrome induced by SEB. We observed that mouse spleen cells treated with IL-15 in ex vivo culture gained a dendritic cell-like phenotype. Administration of IL-15 to mice also resulted in an increased number of mature CD11c+dendritic cells in mouse spleens. A significant, IL-15 dose-dependent increase in antigen-specific antibody was observed after coadministration with the vaccine and an aluminum-based adjuvant (alhydrogel). Furthermore, the coadministration of IL-15 with STEBVax and alhydrogel also protected mice from lethal toxic shock above the levels that obtained without IL-15. Thus, the vaccine response enhanced by IL-15 appears to be mediated by mature dendritic cells and results in prevalent seroconversion to Th2-dependent antibodies. This suggests a potential use of IL-15 as an adjuvant for antibody-dependent responses to vaccines.
Gamma/Delta T-Cell Functional Responses Differ after Pathogenic Human Immunodeficiency Virus and Nonpathogenic Simian Immunodeficiency Virus Infections
Authors: Kosub David A. , Lehrman Ginger , Milush Jeffrey M. , Zhou Dejiang , Chacko Elizabeth , Leone Amanda , Gordon Shari , Silvestri Guido , Else James G. , Keiser Philip , Jain Mamta K. , Sodora Donald L. 
Published: November 2007

ABSTRACTThe objective of this study was to functionally assess gamma/delta (γδ) T cells following pathogenic human immunodeficiency virus (HIV) infection of humans and nonpathogenic simian immunodeficiency virus (SIV) infection of sooty mangabeys. γδ T cells were obtained from peripheral blood samples from patients and sooty mangabeys that exhibited either a CD4-healthy (>200 CD4+T cells/μl blood) or CD4-low (<200 CD4 cells/μl blood) phenotype. Cytokine flow cytometry was utilized to assess production of Th1 cytokines tumor necrosis factor alpha and gamma interferon following ex vivo stimulation with either phorbol myristate acetate/ionomycin or the Vδ2 γδ T-cell receptor agonist isopentenyl pyrophosphate. Sooty mangabeys were observed to have higher percentages of γδ T cells in their peripheral blood than humans did. Following stimulation, γδ T cells from SIV-positive (SIV+) mangabeys maintained or increased their ability to express the Th1 cytokines regardless of CD4+T-cell levels. In contrast, HIV-positive (HIV+) patients exhibited a decreased percentage of γδ T cells expressing Th1 cytokines following stimulation. This dysfunction is primarily within the Vδ2+γδ T-cell subset which incurred both a decreased overall level in the blood and a reduced Th1 cytokine production. Patients treated with highly active antiretroviral therapy exhibited a partial restoration in their γδ T-cell Th1 cytokine response that was intermediate between the responses of the uninfected and HIV+patients. The SIV+sooty mangabey natural hosts, which do not proceed to clinical AIDS, provide evidence that γδ T-cell dysfunction occurs in HIV+patients and may contribute to HIV disease progression.
Pathogenesis and Immune Responses in Gnotobiotic Calves after Infection with the Genogroup II.4-HS66 Strain of Human Norovirus
Authors: Souza M. , Azevedo M. S. P. , Jung K. , Cheetham S. , Saif L. J. 
Published: November 2007

ABSTRACTWe previously characterized the pathogenesis of two host-specific bovine enteric caliciviruses (BEC), the GIII.2 norovirus (NoV) strain CV186-OH and the phylogenetically unassigned NB strain, in gnotobiotic (Gn) calves. In this study we evaluated the Gn calf as an alternative animal model to study the pathogenesis and host immune responses to the human norovirus (HuNoV) strain GII.4-HS66. The HuNoV HS66 strain caused diarrhea (five/five calves) and intestinal lesions (one/two calves tested) in the proximal small intestine (duodenum and jejunum) of Gn calves, with lesions similar to, but less severe than, those described for the Newbury agent 2 (NA-2) and NB BEC. Viral capsid antigen was also detected in the jejunum of the proximal small intestine of one of two calves tested by immunohistochemistry. All inoculated calves shed virus in feces (five/five calves), and one/five had viremia. Antibodies and cytokine (proinflammatory, tumor necrosis factor alpha [TNF-α]; Th1, interleukin-12 [IL-12] and gamma interferon [IFN-γ]; Th2, IL-4; Th2/T-regulatory, IL-10) profiles were determined in serum, feces, and intestinal contents (IC) of the HuNoV-HS66-inoculated calves (n= 5) and controls (n= 4) by enzyme-linked immunosorbent assay in the acute (postinoculation day 3 [PID 3]) and convalescent (PID 28) stages of infection. The HuNoV-HS66-specific antibody and cytokine-secreting cells (CSCs) were quantitated by ELISPOT in mononuclear cells of local and systemic tissues at PID 28. Sixty-seven percent of the HuNoV-HS66-inoculated calves seroconverted, and 100% coproconverted with immunoglobulin A (IgA) and/or IgG antibodies to HuNoV-HS66, at low titers. The highest numbers of antibody-secreting cells (ASC), both IgA and IgG, were detected locally in intestine, but systemic IgA and IgG ASC responses also occurred in the HuNoV-HS66-inoculated calves. In serum, HuNoV-HS66 induced higher peaks of TNF-α and IFN-γ at PIDs 2, 7, and 10; of IL-4 and IL-10 at PID 4; and of IL-12 at PIDs 7 and 10, compared to controls. In feces, cytokines increased earlier (PID 1) than in serum and TNF-α and IL-10 were elevated acutely in the IC of the HS66-inoculated calves. Compared to controls, at PID 28 higher numbers of IFN-γ and TNF-α CSCs were detected in mesenteric lymph nodes (MLN) or spleen and Th2 (IL-4) CSCs were elevated in intestine; IL-10 CSCs were highest in spleen. Our study provides new data confirming HuNoV-HS66 replication and enteropathogenicity in Gn calves and reveals important and comprehensive aspects of the host's local (intestine and MLN) and systemic (spleen and blood) immune responses to HuNoV-HS66.
Foot-and-Mouth Disease Virus Forms a Highly Stable, EDTA-Resistant Complex with Its Principal Receptor, Integrin αvβ6: Implications for Infectiousness
Authors: DiCara Danielle , Burman Alison , Clark Stuart , Berryman Stephen , Howard Mark J. , Hart Ian R. , Marshall John F. , Jackson Terry 
Published: November 2007

ABSTRACTThe initial stage of foot-and-mouth disease virus (FMDV) infection is virus binding to cell surface integrins via the RGD motif in the GH loop of the VP1 capsid protein. As for all ligand/integrin interactions, the initial contact between FMDV and its integrin receptors is cation dependent and hence inhibited by EDTA. We have investigated this binding process with RGD-containing peptides derived from the VP1 capsid protein of FMDV and discovered that, upon binding, some of these peptides form highly stable, EDTA-resistant associations with integrin αvβ6. Peptides containing specific substitutions show that this stable binding is dependent on a helical structure immediately C terminal to the RGD and, specifically, two leucine residues at positions RGD +1 and RGD +4. These observations have a biological consequence, as we show further that stable, EDTA-resistant binding to αvβ6 is a property also exhibited by FMDV particles. Thus, the integrin-binding loop of FMDV appears to have evolved to form very stable complexes with the principal receptor of FMDV, integrin αvβ6. An ability to induce such stable complexes with its cellular receptor is likely to contribute significantly to the high infectiousness of FMDV.
Differential Targeting of Nuclear Pore Complex Proteins in Poliovirus-Infected Cells
Authors: Park Nogi , Katikaneni Pavan , Skern Tim , Gustin Kurt E. 
Published: November 2007

ABSTRACT

Poliovirus disrupts nucleocytoplasmic trafficking and results in the cleavage of two nuclear pore complex (NPC) proteins, Nup153 and Nup62. The NPC is a 125-MDa complex composed of multiple copies of 30 different proteins. Here we have extended the analysis of the NPC in infected cells by examining the status of Nup98, an interferon-induced NPC protein with a major role in mRNA export. Our results indicate that Nup98 is targeted for cleavage after infection but that this occurs much more rapidly than it does for Nup153 and Nup62. In addition, we find that cleavage of these NPC proteins displays differential sensitivity to the viral RNA synthesis inhibitor guanidine hydrochloride. Inhibition of nuclear import and relocalization of host nuclear proteins to the cytoplasm were only apparent at later times after infection when all three nucleoporins (Nups) were cleaved. Surprisingly, analysis of the distribution of mRNA in infected cells revealed that proteolysis of Nup98 did not result in an inhibition of mRNA export. Cleavage of Nup98 could be reconstituted by the addition of purified rhinovirus type 2 2A
pro
to whole-cell lysates prepared from uninfected cells, suggesting that the 2A protease has a role in this process in vivo. These results indicate that poliovirus differentially targets subsets of NPC proteins at early and late times postinfection. In addition, targeting of interferon-inducible NPC proteins, such as Nup98, may be an additional weapon in the arsenal of poliovirus and perhaps other picornaviruses to overcome host defense mechanisms.
Integrin α
V
β
3
Binds to the RGD Motif of Glycoprotein B of Kaposi's Sarcoma-Associated Herpesvirus and Functions as an RGD-Dependent Entry Receptor
Authors: Garrigues H. Jacques , Rubinchikova Yelena E. , DiPersio C. Michael , Rose Timothy M. 
Published: November 2007

ABSTRACT

Kaposi's sarcoma-associated herpesvirus (KSHV) envelope-associated glycoprotein B (gB) is involved in the initial steps of binding to host cells during KSHV infection. gB contains an RGD motif reported to bind the integrin α
3
β
1
during virus entry. Although the ligand specificity of α
3
β
1
has been controversial, current literature indicates that α
3
β
1
ligand recognition is independent of RGD. We compared α
3
β
1
to the RGD-binding integrin, α
V
β
3
, for binding to envelope-associated gB and a gB(RGD) peptide. Adhesion assays demonstrated that β
3
-CHO cells overexpressing α
V
β
3
specifically bound gB(RGD), whereas α
3
-CHO cells overexpressing α
3
β
1
did not. Function-blocking antibodies to α
V
β
3
inhibited the adhesion of HT1080 fibrosarcoma cells to gB(RGD), while antibodies to α
3
β
1
did not. Using affinity-purified integrins and confocal microscopy, α
V
β
3
bound to gB(RGD) and KSHV virions, demonstrating direct receptor-ligand interactions. Specific α
V
β
3
antagonists, including cyclic and dicyclic RGD peptides and α
V
β
3
function-blocking antibodies, inhibited KSHV infection by 70 to 80%. Keratinocytes from α
3
-null mice lacking α
3
β
1
were fully competent for infection by KSHV, and reconstitution of α
3
β
1
function by transfection with α
3
cDNA reduced KSHV infectivity from 74% to 55%. Additional inhibitory effects of α
3
β
1
on the cell surface expression of α
V
β
3
and on α
V
β
3
-mediated adhesion of α
3
-CHO cells overexpressing α
3
β
1
were detected, consistent with previous reports of transdominant inhibition of α
V
β
3
function by α
3
β
1
. These observations may explain previous reports of an inhibition of KSHV infection by soluble α
3
β
1
. Our studies demonstrate that α
V
β
3
is a cellular receptor mediating both the cell adhesion and entry of KSHV into target cells through binding the virion-associated gB(RGD).
Cell Factors Stimulate Human Immunodeficiency Virus Type 1 Reverse Transcription In Vitro
Authors: Warrilow David , Meredith Luke , Davis Adam , Burrell Christopher , Li Peng , Harrich David 
Published: November 2007

ABSTRACT
After fusion of the human immunodeficiency virus type 1 (HIV-1) envelope with the host cell membrane, the HIV-1 core enters the cell cytoplasm. Core components are then restructured to form the reverse transcription complex (RTC); the biochemical details of this process are currently unclear. To investigate early RTC formation, we characterized the endogenous reverse transcription activity of virions, which was less efficient than reverse transcription during cell infection and suggested a requirement for a cell factor. The addition of detergent to virions released reverse transcriptase and capsid, and reverse transcription products became susceptible to the action of exogenous nucleases, indicating virion disruption. Disruption was coincident with the loss of the endogenous reverse transcription activity of virions, particularly late reverse transcription products. Consistent with this observation, the use of a modified “spin thru” method, which uses brief detergent exposure, also disrupted virions. The addition of lysates made from mammalian cell lines (Jurkat, HEK293T, and NIH 3T3 cells) to virions delipidated by detergent stimulated late reverse transcription efficiency. A complex with reverse transcription activity that was slower sedimenting than virions on a velocity gradient was greatly stimulated to generate full-length reverse transcription products and was associated with only relatively small amounts of capsid. These experiments suggest that cell factors are required for efficient reverse transcription of HIV-1.
Establishment of Canine RNA Polymerase I-Driven Reverse Genetics for Influenza A Virus: Its Application for H5N1 Vaccine Production
Authors: Murakami Shin , Horimoto Taisuke , Yamada Shinya , Kakugawa Satoshi , Goto Hideo , Kawaoka Yoshihiro 
Published: November 2007

ABSTRACT
In the event of a new influenza pandemic, vaccines whose antigenicities match those of circulating strains must be rapidly produced. Here, we established an alternative reverse genetics system for influenza virus using the canine polymerase I (PolI) promoter sequence that works efficiently in the Madin-Darby canine kidney cell line, a cell line approved for human vaccine production. Using this system, we were able to generate H5N1 vaccine seed viruses more efficiently than can be achieved with the current system that uses the human PolI promoter in African green monkey Vero cells, thus improving pandemic vaccine production.
Work in the textile industry in Spain and bladder cancer
Authors: Serra C , Kogevinas M , Silverman D T , Turuguet D , Tardon A , Garcia-Closas R , Carrato A , Castaño-Vinyals G , Fernandez F , Stewart P , Benavides F G , Gonzalez S , Serra A , Rothman N , Malats N , Dosemeci M 
Published: November 2007

Background/objective:Textile manufacturing is a complex industry that has frequently been associated with bladder cancer. However, results have not been consistent. This study investigated the risk of bladder cancer in Spanish textile workers.Methods:We analysed data from a multicentre hospital-based case-control study carried out in Spain (1998–2001) including 1219 cases of bladder cancer and 1271 controls. Of those, 126 cases and 122 controls reported a history of employment in the textile industry. Lifetime occupational history was obtained using a computer-assisted personal interview. Occupations, locations and materials used in the textile industry were assessed using a detailed questionnaire and expert assessment.Results:Overall, no increased risk of bladder cancer was found for textile workers, including duration of employment analysis. Increased risks were observed for weavers (OR  = 1.82, 95% CI 0.95 to 3.47), for workers in winding/warping/sizing (OR 4.11, 95% CI 1.58 to 10.71) and for those exposed to synthetic materials (OR 1.89, 95% CI 1.00 to 3.56). Working for more than 10 years appeared to be associated with an increased risk for weavers (OR 2.27, 95% CI 0.97 to 5.34), for those who had ever worked in winding/warping/sizing (OR 11.03, 95% CI 1.37, 88.89), for workers in the weaving room (OR 2.94, 95% CI 1.24 to 7.01) and for those exposed to synthetic (OR 2.62, 95% CI 1.14 to 6.01) or cotton (OR 2.00, 95% CI 1.04 to 3.87) materials. Statistically significant higher risks were also found for specific combinations of occupations or locations with exposure to synthetics and cotton.Conclusions:There was no overall increased risk for textile workers, but increased risks were found for specific groups of workers. Our findings indicate that observed risks in previous studies may be better evaluated by analysis of materials used or section worked within the industry and occupation.
Smoking cessation attempts among adolescent smokers: a systematic review of prevalence studies
Authors: Bancej Christina , O’Loughlin Jennifer , Platt Robert W , Paradis Gilles , Gervais André 
Published: November 2007

Objective:To synthesise estimates of the prevalence of cessation attempts among adolescent smokers generally, and according to age and level of cigarette consumption.Data sources:PubMed, ERIC, and PsychInfo databases and Internet searches of central data collection agencies.Study selection:National population-based studies published in English between 1990 and 2005 reporting the prevalence, frequency and/or duration of cessation attempts among smokers aged ⩾10 to <20 years.Data extraction:Five reviewers determined inclusion criteria for full-text reports. One reviewer extracted data on the design, population characteristics and results from the reports.Data synthesis:In total, 52 studies conformed to the inclusion criteria. The marked heterogeneity that characterised the study populations and survey questions precluded a meta-analysis. Among adolescent current smokers, the median 6-month, 12-month and lifetime cessation attempt prevalence was 58% (range: 22–73%), 68% (range 43–92%) and 71% (range 28–84%), respectively. More than half had made multiple attempts. Among smokers who had attempted cessation, the median prevalence of relapse was 34, 56, 89 and 92% within 1 week, 1 month, 6 months, and 1 year, respectively, following the longest attempt. Younger (age<16 years) and non-daily smokers experienced a similar or higher prevalence of cessation attempts compared with older (age ⩾16 years) or daily smokers. Moreover, the prevalence of relapse by 6 months following the longest cessation attempt was similar across age and smoking frequency.Conclusions:The high prevalence of cessation attempts and relapse among adolescent smokers extends to young adolescents and non-daily smokers. Cessation surveillance, research and program development should be more inclusive of these subgroups.
“I always thought they were all pure tobacco”: American smokers’ perceptions of “natural” cigarettes and tobacco industry advertising strategies
Authors: McDaniel Patricia A , Malone Ruth E 
Published: November 2007

Objective:To examine how the US tobacco industry markets cigarettes as “natural” and American smokers’ views of the “naturalness” (or unnaturalness) of cigarettes.Methods:Internal tobacco industry documents, the Pollay 20th Century Tobacco Ad Collection, and newspaper sources were reviewed, themes and strategies were categorised, and the findings were summarised.Results:Cigarette advertisements have used the term “natural” since at least 1910, but it was not until the 1950s that “natural” referred to a core element of brand identity, used to describe specific product attributes (filter, menthol, tobacco leaf). The term “additive-free”, introduced in the 1980s, is now commonly used to define natural cigarettes. Tobacco company market research, available from 1970 to 1998, consistently revealed that within focus group sessions, smokers initially had difficulty interpreting the term “natural” in relation to cigarettes; however, after discussion of cigarette ingredients, smokers viewed “natural” cigarettes as healthier. Tobacco companies regarded the implied health benefits of natural cigarettes as their key selling point, but hesitated to market them because doing so might raise doubts about the composition of their highly profitable “regular” brands.Conclusion:Although our findings support the idea advanced by some tobacco control advocates that informing smokers of conventional cigarettes’ chemical ingredients could promote cessation, they also suggest that such a measure could increase the ubiquity and popularity of “natural” cigarettes. A more effective approach may be to “denaturalise” smoking.
Is a statewide tobacco quitline an appropriate service for specific populations?
Authors: Maher Julie E , Rohde Kristen , Dent Clyde W , Stark Michael J , Pizacani Barbara , Boysun Michael J , Dilley Julia A , Yepassis-Zembrou Patricia L 
Published: November 2007

Objective:To assess whether smoking quit rates and satisfaction with the Washington State tobacco quitline (QL) services varied by race/ethnicity, socioeconomic status, area of residence (that is, urban versus non-urban), or sex of Washington QL callers.Methods:From October 2004 into October 2005, we conducted telephone surveys of Washington QL callers about three months after their initial call to the QL. Analyses compared 7-day quit rates and satisfaction measures by race/ethnicity, education level, area of residence and sex (using α = 0.05).Results:We surveyed half (n = 1312) of the 2638 adult smokers we attempted to contact. The 7-day quit rate among survey participants at the 3-month follow-up was 31% (CI: 27.1% to 34.2%), 92% (CI: 89.9% to 94.1%) were somewhat/very satisfied overall with the QL programme, 97% (CI: 95.5% to 98.2%) indicated that they would probably/for sure suggest the QL to others and 95% (CI: 92.9% to 96.4%) were somewhat/very satisfied with the QL specialist. Quit rate did not vary significantly by race/ethnicity, education level, area of residence or sex. Satisfaction levels were high across subpopulations. Almost all participants (99%) agreed that they were always treated respectfully during interactions with QL staff.Conclusions:The Washington QL appeared effective and well received by callers from the specific populations studied. States choosing to promote their QL more aggressively should feel confident that a tobacco QL can be an effective and well received cessation service for smokers who call from a broad range of communities.
The association between advertising and calls to a tobacco quitline
Authors: Mosbaek Craig H , Austin Donald F , Stark Michael J , Lambert Lori C 
Published: November 2007

Objective:This study assessed the cost effectiveness of different types of television and radio advertisements and the time of day in which advertisements were placed in generating calls to the Oregon tobacco quitline.Design:Cost effectiveness was measured by cost per call, calculated as the cost of advertising divided by the number of quitline calls generated by that advertising. Advertising was bought in one-week or two-week blocks and included 27 daytime television buys, 22 evening television buys and 31 radio buys.Results:Cost effectiveness varied widely by medium, time of day and advertisement used. Daytime television was seven times more cost effective than evening television and also more cost effective than radio. The most effective advertisements at generating quitline calls were real life testimonials by people who lost family members to tobacco and advertisements that deal practically with how to quit.Conclusions:Placement of television advertisements during the day versus the evening can increase an advertisement’s effectiveness in generating calls to a quitline. Some advertising messages were more effective than others in generating calls to a quitline. Quitline providers can apply findings from previous research when planning media campaigns. In addition, call volume should be monitored in order to assess the cost effectiveness of different strategies to promote use of the quitline.