bluuebunny/crossref_metadata_2025_split huggingface dataset:
InactivatedFrancisella tularensisLive Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion
Authors: Baron Shawn D. , Singh Rajendra , Metzger Dennis W. 
Published: February 2007

ABSTRACTFrancisella tularensisis a gram-negative intracellular bacterium that is considered to be a potential category A biological weapon due to its extreme virulence. Although vaccination with the attenuated live vaccine strain (LVS) ofF. tularensiscan protect against lethal challenge, use of inactivated or subunit forms as vaccine candidates for induction of protective antibody responses has not been fully evaluated. In the present study, we examined whether immune protection in the lung could be stimulated by intranasal administration of inactivated LVS together with interleukin-12 (IL-12) as an adjuvant. LVS was inactivated by heat, paraformaldehyde treatment, or exposure to UV, and inactivation of the preparations was confirmed by assessing bacterial growth and the survival of mice after direct inoculation. We found that mucosal vaccination with inactivated LVS provided 90 to 100% protection in mice after lethal intranasal challenge with 104CFU of LVS, and this protection was dependent on inclusion of exogenous IL-12 during vaccine administration. Survival of vaccinated mice after live bacterial challenge was correlated with reduced bacterial burden, decreased pulmonary inflammation, increased serum antibody titers, and lower levels of gamma interferon (IFN-γ), tumor necrosis factor alpha, and IL-6 in the lungs, livers, and spleens. Whereas NK cells were primarily responsible for the production of IFN-γ in unvaccinated, challenged animals, vaccinated mice had increased levels of lung IFN-γ+CD4+T cells after challenge. Significantly, mice genetically deficient in immunoglobulin A (IgA) expression were unable to survive lethal challenge after vaccination. These results are the first results to demonstrate that IgA-mediated protection against lethal respiratory tularemia occurs after mucosal vaccination with inactivatedF. tularensisLVS.
Physiological Osmotic Induction of
Leptospira interrogans
Adhesion: LigA and LigB Bind Extracellular Matrix Proteins and Fibrinogen
Authors: Choy Henry A. , Kelley Melissa M. , Chen Tammy L. , Møller Annette K. , Matsunaga James , Haake David A. 
Published: February 2007

ABSTRACT

Transmission of leptospirosis occurs through contact of mucous membranes and abraded skin with freshwater contaminated by pathogenic
Leptospira
spp. Exposure to physiological osmolarity induces leptospires to express high levels of the Lig surface proteins containing imperfect immunoglobulin-like repeats that are shared or differ between LigA and LigB. We report that osmotic induction of Lig is accompanied by 1.6- to 2.5-fold increases in leptospiral adhesion to immobilized extracellular matrix and plasma proteins, including collagens I and IV, laminin, and especially fibronectin and fibrinogen. Recombinant LigA-unique and LigB-unique repeat proteins bind to these same host ligands. We found that the avidity of LigB in binding fibronectin is comparable to that of the
Staphylococcus aureus
FnBPA D repeats. Both LigA- and LigB-unique repeats interact with the amino-terminal fibrin- and gelatin-binding domains of fibronectin, which are also recognized by fibronectin-binding proteins mediating the adhesion of other microbial pathogens. In contrast, repeats common to both LigA and LigB do not bind these host proteins, and nonrepeat sequences in the carboxy-terminal domain of LigB show only weak interaction with fibronectin and fibrinogen. A functional role for the binding activity of LigA and LigB is suggested by the ability of the recombinants to inhibit leptospiral adhesion to fibronectin by 28% and 21%, respectively. The binding of LigA and LigB to multiple ligands present in different tissues suggests that these adhesins may be involved in the initial colonization and dissemination stages of leptospirosis. The characterization of the Lig adhesin function should aid the design of Lig-based vaccines and serodiagnostic tests.
Nasal Immunization withBurkholderia multivoransOuter Membrane Proteins and the Mucosal Adjuvant Adamantylamide Dipeptide Confers Efficient Protection against Experimental Lung Infections withB. multivoransandB. cenocepacia
Authors: Bertot Gustavo M. , Restelli Marcela A. , Galanternik Laura , Aranibar Urey Rene C. , Valvano Miguel A. , Grinstein Saúl 
Published: February 2007

ABSTRACTChronic lung infection by opportunistic pathogens, such asPseudomonas aeruginosaand members of theBurkholderia cepaciacomplex, is a major cause of morbidity and mortality in patients with cystic fibrosis. Outer membrane proteins (OMPs) of gram-negative bacteria are promising vaccine antigen candidates. In this study, we evaluated the immunogenicity, protection, and cross-protection conferred by intranasal vaccination of mice with OMPs fromB. multivoransplus the mucosal adjuvant adamantylamide dipeptide (AdDP). Robust mucosal and systemic immune responses were stimulated by vaccination of naive animals with OMPs fromB. multivoransandB. cenocepaciaplus AdDP. Using a mouse model of chronic pulmonary infection, we observed enhanced clearance ofB. multivoransfrom the lungs of vaccinated animals, which correlated with OMP-specific secretory immunoglobulin A responses. Furthermore, OMP-immunized mice showed rapid resolution of the pulmonary infection with virtually no lung pathology after bacterial challenge withB. multivorans. In addition, we demonstrated that administration ofB. multivoransOMP vaccine conferred protection againstB. cenocepaciachallenge in this mouse infection model, suggesting that OMPs provide cross-protection against theB. cepaciacomplex. Therefore, we concluded that mucosal immunity toB. multivoranselicited by intranasal vaccination with OMPs plus AdDP could prevent early steps of colonization and infection withB. multivoransand also ameliorate lung tissue damage, while eliciting cross-protection againstB. cenocepacia. These results support the notion that therapies leading to increased mucosal immunity in the airways may help patients with cystic fibrosis.
Immunization of Pigs To Prevent Disease in Humans: Construction and Protective Efficacy of a
Salmonella enterica
Serovar Typhimurium Live Negative-Marker Vaccine
Authors: Selke Martin , Meens Jochen , Springer Sven , Frank Ronald , Gerlach Gerald-F. 
Published: February 2007

ABSTRACT

Zoonotic infections caused by
Salmonella enterica
serovar Typhimurium pose a constant threat to consumer health, with the pig being a particularly major source of multidrug-resistant isolates. Vaccination, as a promising approach to reduce colonization and shedding, has been scarcely used, as it interferes with current control programs relying on serology as a means of herd classification. In order to overcome this problem, we set out to develop a negative-marker vaccine allowing the differentiation of infected from vaccinated animals (DIVA). Applying an immunoproteomic approach with two-dimensional gel electrophoresis, Western blot, and quadrupole time-of-flight tandem mass spectrometry, we identified the OmpD protein as a suitable negative marker. Using allelic exchange, we generated an isogenic mutant of the licensed live vaccine strain Salmoporc and showed that virulence of Salmoporc and that of the mutant strain, SalmoporcΔ
ompD
, were indistinguishable in BALB/c mice. In a pig infection experiment including two oral immunizations with SalmoporcΔ
ompD
and challenge with a multiresistant
S. enterica
serovar Typhimurium DT104 clinical isolate, we confirmed the protective efficacy of SalmoporcΔ
ompD
in pigs, showing a significant reduction of both clinical symptoms and colonization of lymph nodes and intestinal tract. OmpD immunogenic epitopes were determined by peptide spot array analyses. Upon testing of several 9-mer peptides, each including an immunogenic epitope, one peptide (positions F
100
to Y
108
) that facilitated the detection of infected animals independent of their vaccination status (DIVA function) was identified. The approach described overcomes the problems currently limiting the use of bacterial live vaccines and holds considerable potential for future developments in the field.
Cryoglobulinaemic vasculitis: classification and clinical and therapeutic aspects
Authors: Braun Gerald S , Horster Sophia , Wagner Katrin S , Ihrler Stephan , Schmid Holger 
Published: February 2007

Abstract
Cryoglobulinaemia may cause cutaneous vasculitis and glomerulonephritis, potentially leading to end stage renal failure. An important proportion of cryoglobulinaemias are secondary to hepatitis C virus infection. Emerging antiviral treatment options offer a chance for causal therapy of these cases of cryoglobulinaemia. This review summarises the classification and clinical and therapeutic aspects of cryoglobulinaemic vasculitis and glomerulonephritis.
Media advocacy, tobacco control policy change and teen smoking in Florida
Authors: Niederdeppe Jeff , Farrelly Matthew C , Wenter Dana 
Published: February 2007

Objective:To assess whether media advocacy activities implemented by the Florida Tobacco Control Program contributed to increased news coverage, policy changes and reductions in youth smoking.Methods:A content analysis of news coverage appearing in Florida newspapers between 22 April 1998 and 31 December 2001 was conducted, and patterns of coverage before and after the implementation of media advocacy efforts to promote tobacco product placement ordinances were compared. Event history analysis was used to assess whether news coverage increased the probability of enacting these ordinances in 23 of 67 Florida counties and ordinary least square (OLS) regression was used to gauge the effect of these policies on changes in youth smoking prevalence.Results:The volume of programme-related news coverage decreased after the onset of media advocacy efforts, but the ratio of coverage about Students Working Against Tobacco (the Florida Tobacco Control Program’s youth advocacy organisation) relative to other topics increased. News coverage contributed to the passage of tobacco product placement ordinances in Florida counties, but these ordinances did not lead to reduced youth smoking.Conclusion:This study adds to the growing literature supporting the use of media advocacy as a tool to change health-related policies. However, results suggest caution in choosing policy goals that may or may not influence health behaviour.
Revising the machine smoking regime for cigarette emissions: implications for tobacco control policy
Authors: Hammond David , Wiebel Friedrich , Kozlowski Lynn T , Borland Ron , Cummings K Michael , O’Connor Richard J , McNeill Ann , Connolly Greg N , Arnott Deborah , Fong Geoffrey T 
Published: February 2007

Background:The WHO Framework Convenion on Tobacco Control includes provisions for testing and regulating cigarette emissions. However, the current international standard for generating cigarette emissions—the ISO machine smoking regime—is widely acknowledged to be inappropriate for purposes of setting regulatory restrictions.Objective:To review alternatives to the ISO machine smoking regime and the extent to which they: 1) Represent human smoking behaviour, 2) Reduce the potential for industry exploitation, particularly in the area of risk communication, and 3) Serve as suitable measures for product regulation.Methods:Emissions data from 238 Canadian cigarette brands tested under the ISO and “Canadian Intense” machine smoking regimes.Results:None of the alternative smoking regimes, including the Canadian Intense method, are more “representative” of human smoking behaviour and none provide better predictors of human exposure.Conclusions:Given that alternatives such as the Canadian Intense regime are subject to the same fundamental limitations as the ISO regime, key questions need to be addressed before any smoking regime should be used to set regulatory limits on smoke emissions. In the meantime, regulators should remove quantitative emission values from cigarette packages and more work should be done on alternative machine smoking methods.
“The law was actually drafted by us but the Government is to be congratulated on its wise actions”: British American Tobacco and public policy in Kenya: Table 1
Authors: Patel Preeti , Collin Jeff , Gilmore Anna B 
Published: February 2007

Background and objective:British American Tobacco (BAT) has historically enjoyed a monopoly position in Kenya. Analysis of recent tobacco control debates and a case study of BAT’s response to the emergence of competition in Kenya are used to explore the company’s ability to shape public policy and its treatment of tobacco farmers.Design:Analysis of internal industry documents from BAT’s Guildford depository, other relevant data and interviews with key informants.Results:BAT enjoys extensive high-level political connections in Kenya, including close relationships with successive Kenyan presidents. Such links seems to have been used to influence public policy. Health legislation has been diluted and delayed, and when a competitor emerged in the market, BAT used its contacts to have the government pass legislation drafted by BAT that compelled farmers to sell tobacco to BAT rather than to its competitor. BAT was already paying farmers less than any other African leaf-growing company, and the legislation entrenched poor pay and a quasi-feudal relationship. BAT’s public relation’s response to the threat of competition and the ministers’ public statements extolling the economic importance of tobacco growing suggest that BAT has manipulated tobacco farming as a political issue.Conclusions:The extent of BAT’s influence over public policy is consistent with the observations that, despite ratifying the Framework Convention on Tobacco Control, progress in implementing tobacco control measures in Kenya has been limited. The benefits of tobacco farming seem to be deliberately exaggerated, and an analysis of its true cost benefits is urgently needed. Tobacco farmers must be protected against BAT’s predatory practices and fully informed about its activities to help them have an informed role in policy debates. As image, particularly around the importance of tobacco farming, seems key to BAT’s ability to influence policy, the truth about its treatment of farmers must be publicised.
Economic effect of a smoke-free law in a tobacco-growing community: Table 1
Authors: Pyles Mark K , Mullineaux Donald J , Okoli Chizimuzo T C , Hahn Ellen J 
Published: February 2007

Objective:To determine whether Lexington, Kentucky’s smoke-free law affected employment and business closures in restaurants and bars. On 27 April 2004, Lexington-Fayette County implemented a comprehensive ordinance prohibiting smoking in all public buildings, including bars and restaurants. Lexington is located in a major tobacco-growing state that has the highest smoking rate in the US and was the first Kentucky community to become smoke-free.Design:A fixed-effects time series design to estimate the effect of the smoke-free law on employment and ordinary least squares to estimate the effect on business openings and closings.Subjects and settings:All restaurants and bars in Lexington-Fayette County, Kentucky and the six contiguous counties.Main outcome measures:ES-202 employment data from the Kentucky Workforce Cabinet; Business opening/closings data from the Lexington-Fayette County Health Department, Environmental Division.Results:A positive and significant relationship was observed between the smoke-free legislation and restaurant employment, but no significant relationship was observed with bar employment. No relationship was observed between the law’s implementation and employment in contiguous counties nor between the smoke-free law and business openings or closures in alcohol-serving and or non-alcohol-serving businesses.Conclusions:No important economic harm stemmed from the smoke-free legislation over the period studied, despite the fact that Lexington is located in a tobacco-producing state with higher-than-average smoking rates.
Five in a row—reactions of smokers to tobacco tax increases: population-based cross-sectional studies in Germany 2001–2006
Authors: Hanewinkel Reiner , Isensee Barbara 
Published: February 2007

Objective:To assess reactions of smokers to five waves of tobacco tax increases in Germany.Design:A 10-wave cross-sectional study, with assessments before and after the tax increases.Setting:General population of Germany.Participants and methods:10 representative samples from the general population with a total number of 27 608 people aged ⩾14 years, including 8548 smokers (31% of the total sample), were interviewed.Outcome measures:Reflection on smoking behaviour, and smoking behaviour (quitting, reducing, switching to a cheaper brand or no change) before and after tobacco tax increases.Results:Before the tax increases, one third to more than half of the smokers reflected on their smoking behaviour, 9.7–13.9% intended to quit, 23.4–34.7% intended to reduce smoking and 10.8–16.4% intended to switch to cheaper tobacco products, whereas 36.1–52.1% did not intend any change at all. After the tax increases, one fourth to more than one third reported to have reflected on their smoking behaviour, 4.0–7.9% quit smoking owing to the increase, 11.5–16.6% reduced consumption and 11.0–19.9% switched to cheaper products. Significant associations were found between the height of the price increase and the intentions and reactions of smokers.Conclusions:Price increases lead to a substantial reflection on smoking and intended and realised behaviour changes such as reduced consumption and switching to cheaper tobacco products. These effects are more pronounced the more the price rises. Therefore, taxation policy will lead to quitting and reducing smoking. However, complementary measures should also be taken to prevent smokers switching to cheaper tobacco products, which would reduce the effectiveness of taxation policy.
Death at a discount: how the tobacco industry thwarted tobacco control policies in US military commissaries
Authors: Smith Elizabeth A , Blackman Viginia S , Malone Ruth E 
Published: February 2007

Background:The US military is perhaps the only retailer consistently losing money on tobacco. Military stores (commissaries and exchanges) have long sold discount-priced cigarettes, while the Department of Defense (DoD) pays directly for tobacco-related healthcare costs of many current and former customers. Tobacco use also impairs short-term troop readiness.Objective:To examine the long struggle to raise commissary tobacco prices and the tobacco industry’s role in this policy effort.Methods:Analysis of internal tobacco industry documents, searches of government and military websites and newspaper databases, and interviews with key informants identified in the documents.Results:Efforts to raise commissary tobacco prices began in the mid-1980s. Opposition quickly emerged. Some military officials viewed tobacco use as a “right” and low prices as a “benefit”. Others raised issues of authority, and some saw the change as threatening the stores. The tobacco industry successfully exploited complex relationships among the Congress, the DoD, commissaries, exchanges and private industry, obstructing change for over a decade. Leadership from the Secretary and Assistant Secretaries of Defense, presidential support and procedural manoeuvring finally resulted in a modest price increase in 1996, but even then, high-level military officials were apparently threatened with retaliation from pro-tobacco Congressmen.Conclusions:The longstanding military tradition of cheap cigarettes persists because of the politics of the military sales system, the perception within the military of tobacco use as a right, and tobacco industry pressures. Against its own best interests, the US military still makes tobacco available to service members at prices below those in the civilian sector.
Tobacco-related disease mortality among men who switched from cigarettes to spit tobacco
Authors: Henley S Jane , Connell Cari J , Richter Patricia , Husten Corinne , Pechacek Terry , Calle Eugenia E , Thun Michael J 
Published: February 2007

Background:Although several epidemiological studies have examined the mortality among users of spit tobacco, none have compared mortality of former cigarette smokers who substitute spit tobacco for cigarette smoking (“switchers”) and smokers who quit using tobacco entirely.Methods:A cohort of 116 395 men were identified as switchers (n = 4443) or cigarette smokers who quit using tobacco entirely (n = 111 952) when enrolled in the ongoing US American Cancer Society Cancer Prevention Study II. From 1982 to 31 December 2002, 44 374 of these men died. The mortality hazard ratios (HR) of tobacco-related diseases, including lung cancer, coronary heart disease, stroke and chronic obstructive pulmonary disease, were estimated using Cox proportional hazards regression modelling adjusted for age and other demographic variables, as well as variables associated with smoking history, including number of years smoked, number of cigarettes smoked and age at quitting.Results:After 20 years of follow-up, switchers had a higher rate of death from any cause (HR 1.08, 95% confidence interval (CI) 1.01 to 1.15), lung cancer (HR 1.46, 95% CI 1.24 to 1.73), coronary heart disease (HR 1.13, 95% CI 1.00 to 1.29) and stroke (HR 1.24, 95% CI 1.01 to 1.53) than those who quit using tobacco entirely.Conclusion:The risks of dying from major tobacco-related diseases were higher among former cigarette smokers who switched to spit tobacco after they stopped smoking than among those who quit using tobacco entirely.
Extensive Immunoglobulin Production Sensitizes Myeloma Cells for Proteasome Inhibition
Authors: Meister Silke , Schubert Ulrich , Neubert Kirsten , Herrmann Kai , Burger Renate , Gramatzki Martin , Hahn Sabine , Schreiber Sandra , Wilhelm Sabine , Herrmann Martin , Jäck Hans-Martin , Voll Reinhard E. 
Published: February 2007

AbstractMultiple myeloma is an incurable plasma cell neoplasia characterized by the production of large amounts of monoclonal immunoglobulins. The proteasome inhibitor bortezomib (PS-341, Velcade) induces apoptosis in various malignant cells and has been approved for treatment of refractory multiple myeloma. Inhibition of the antiapoptotic transcription factor nuclear factor-κB (NF-κB) apparently contributes to the antitumor effects of bortezomib; however, this mechanism cannot fully explain the exceptional sensitivity of myeloma cells. Extensive protein synthesis as in myeloma cells is inherently accompanied by unfolded proteins, including defective ribosomal products (DRiPs), which need to be degraded by the ubiquitin-proteasome system. Therefore, we hypothesized that the proapoptotic effect of bortezomib in multiple myeloma is mainly due to the accumulation of unfolded proteins in cells with high protein biosynthesis. Using the IgG-secreting human myeloma cell line JK-6L and murine μH-chain–transfected Ag8.H myeloma cells, apoptosis induction upon proteasome inhibition was clearly correlated with the amount of immunoglobulin production. Preferentially in immunoglobulin-high myeloma cells, bortezomib triggered activation of caspases and induction of proapoptotic CHOP, a component of the terminal unfolded protein response induced by endoplasmic reticulum (ER) stress. In immunoglobulin-high cells, bortezomib increased the levels of proapoptotic Bax while reducing antiapoptotic Bcl-2. Finally, IgG-DRiPs were detected in proteasome inhibitor–treated cells. Hence, proteasome inhibitors induce apoptosis preferentially in cells with high synthesis rate of immunoglobulin associated with accumulation of unfolded proteins/DRiPs inducing ER stress. These findings further elucidate the antitumor activities of proteasome inhibitors and have important implications for optimizing clinical applications. [Cancer Res 2007;67(4):1783–92]