bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimization ofSalmonella entericaSerovar Typhi ΔaroCΔssaVDerivatives as Vehicles for Delivering Heterologous Antigens by Chromosomal Integration and In Vivo Inducible Promoters
Authors: Stratford Richard , McKelvie Nicola D. , Hughes Nicky J. , Aldred Emma , Wiseman Claire , Curtis Johanna , Bellaby Trevor , Bentley Matt , Hindle Zoë , Brennan Frank R. , Chatfield Steven N. , Dougan Gordon , Khan Shahid A. 
Published: December 2004

ABSTRACTNovel candidate live oral vaccines based on aSalmonella entericaserovar Typhi ZH9 (Ty2 ΔaroCΔssaV) derivative that directed the expression of either the B subunit ofEscherichia coliheat-labile toxin or hepatitis B virus core antigen from the bacterial chromosome using the in vivo induciblessaGpromoter were constructed. The levels of attenuation of the twoS. entericaserovar Typhi ZH9 derivatives were similar to that of the parent as assessed by measuring the replication of bacteria within human macrophage-like U937 cells. The expression of heterologous antigen in the respectiveS. entericaserovar Typhi ZH9 derivatives was up-regulated significantly within U937 cells compared to similarS. entericaserovar Typhi ZH9 derivative bacteria grown in modified Luria-Bertani broth supplemented with aromatic amino acids. Immunization of mice with theseS. entericaserovar Typhi ZH9 derivatives stimulated potent antigen-specific serum immunoglobulin G responses to the heterologous antigens.
Use of Phage Display To Identify Potential
Pseudomonas aeruginosa
Gene Products Relevant to Early Cystic Fibrosis Airway Infections
Authors: Beckmann Christiane , Brittnacher Mitchell , Ernst Robert , Mayer-Hamblett Nicole , Miller Samuel I. , Burns Jane L. 
Published: December 2004

ABSTRACT

Pseudomonas aeruginosa
airway infections are a major cause of morbidity and mortality in patients with cystic fibrosis. Treatment of established infections is difficult, even with microbiologically active agents. Thus, prevention of infection is an important goal of management. Isolates from cystic fibrosis patients appear to originate from the environment but adapt to the milieu of the airway of the cystic fibrosis patient and evolve toward a common phenotype. Identification of the antigens expressed early in infection may lead to novel targets for vaccine development. Immunogenic peptides were identified in a J404 random nonapeptide phage display library with serum from cystic fibrosis patients obtained within the first year of
P. aeruginosa
infection. One hundred sixty-five reactive clones were verified by plaque lift assays, and their inserts were sequenced. The sequenced nonapeptides were compared with the published sequence of strain PAO1, identifying homologies to 76 genes encoding outer membrane and secreted proteins. The majority of these were proteins involved in small-molecule transport, membrane structural proteins, and secreted factors. An in silico analysis was performed that suggested that the occurrence of multiple matches to predominantly outer membrane and secreted proteins was not attributable to random chance. Finally, gene expression array data from early isolates of
P. aeruginosa
from cystic fibrosis patients was compared with the results from phage display analysis. Eleven outer membrane and secreted proteins were common between the two data sets. These included genes involved in iron acquisition, antibiotic efflux, fimbrial biogenesis, and pyocin synthesis. These results demonstrate the feasibility and validity of this novel approach and suggest potential targets for future development.
Abundant Secretion of Bioactive Interleukin-1β by Human Macrophages Induced byActinobacillus actinomycetemcomitansLeukotoxin
Authors: Kelk P. , Claesson R. , Hänström L. , Lerner U. H. , Kalfas S. , Johansson A. 
Published: December 2004

ABSTRACTActinobacillus actinomycetemcomitansproduces a leukotoxin that selectively kills human leukocytes. Recently, we reported that macrophages are highly sensitive to leukotoxin and that their lysis involves activation of caspase 1. In this study, we show that leukotoxin also induces the production and release of proinflammatory cytokines from human macrophages. The macrophages were challenged with leukotoxin or lipopolysaccharide (LPS) fromA. actinomycetemcomitansor LPS fromEscherichia coli, and the production and secretion of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α) were determined at the mRNA and protein levels by reverse transcription-PCR and enzyme-linked immunosorbent assay, respectively. Leukotoxin (1 to 30 ng/ml) induced abundant production and secretion of IL-1β, while the effects on IL-6 and TNF-α production were limited. Leukotoxin (1 ng/ml) caused a 10-times-higher release of IL-1β than did LPS (100 ng/ml). The secreted IL-1β was mainly the bioactive 17-kDa protein. At higher concentrations (>30 ng/ml), leukotoxin caused secretion of mainly inactive cytokine, the 31-kDa pro-IL-1β. The presence of specific antibodies to IL-1β or of a caspase 1 inhibitor blocked the secretion and production of the cytokine. Supernatants of leukotoxin-challenged macrophages stimulated bone resorption when tested in a mouse calvarial model. The activity could be blocked by an IL-1 receptor antagonist or specific antibodies to IL-1β. We concluded thatA. actinomycetemcomitansleukotoxin can trigger abundant production and secretion of bioactive IL-1β by human macrophages, which is mediated by activation of caspase 1.
Functional Regions of thePseudomonas aeruginosaCytotoxin ExoU
Authors: Rabin Shira D. P. , Hauser Alan R. 
Published: December 2004

ABSTRACTExoU, a potent patatin-like phospholipase, causes rapid cell death following its injection into host cells by thePseudomonas aeruginosatype III secretion system. To better define regions of ExoU required for cytotoxicity, transposon-based linker insertion mutagenesis followed by site-directed mutagenesis of individual residues was employed by using aSaccharomyces cerevisiaemodel system. Random insertion of five amino acids identified multiple regions within ExoU that are required for cell killing. Five regions were chosen for further characterization: three corresponded to the oxyanion hole, hydrolase motif, and catalytic aspartate motif of the patatin-like domain within the N-terminal half of ExoU; one corresponded to an uncharacterized part of the patatin-like domain; and one corresponded to a region near the C terminus. Specific individual amino acid substitutions in each of the four N-terminal regions prevented killing of yeast and significantly reduced phospholipase activity. Whereas five amino acid insertions in the fifth region near the C terminus markedly reduced cytotoxicity and phospholipase activity, substitution of individual amino acids did not abolish either activity. To determine whether each of the five identified regions of ExoU was also essential for cytotoxicity in human cells, representative mutant forms of ExoU fused to green fluorescent protein were expressed in HeLa cells. These variants of ExoU were readily visualized and caused minimal cytotoxicity to HeLa cells, while wild-type ExoU fused to green fluorescent protein induced significant cell lysis and no detectable fluorescence. Thus, a minimum of five regions, including one which is well removed from the patatin-like domain, are required for the cytotoxicity and phospholipase activity of ExoU.
Characterization of an ExoS Type III Translocation-Resistant Cell Line
Authors: Rucks Elizabeth A. , Olson Joan C. 
Published: December 2004

ABSTRACTPseudomonas aeruginosaExoS is a type III-secreted type III-secreted, bifunctional protein that causes diverse effects on eukaryotic cell function. The coculture ofP. aeruginosastrains expressing ExoS with HL-60 myeloid cells revealed the cell line to be resistant to the toxic effects of ExoS. Differentiation of HL-60 cells with phorbol 12-myristate 13-acetate (TPA) rendered the cell line sensitive to ExoS. To understand the cellular basis for the alteration in sensitivity, undifferentiated and TPA-differentiated HL-60 cells were compared for differences in bacterial adherence, type III secretion induction, and ExoS translocation. These comparisons found that ExoS was translocated more efficiently in TPA-differentiated HL-60 cells than in undifferentiated cells. The studies support the ability of eukaryotic cells to influenceP. aeruginosaTTS at the level of membrane translocation.
Reduced Local Growth and Spread but Preserved Pathogenicity of a Δ
purC Mycobacterium tuberculosis
Auxotrophic Mutant in Gamma Interferon Receptor-Deficient Mice after Aerosol Infection
Authors: Brown Najmeeyah , Jacobs Muazzam , Parida Shreemanta K. , Botha Tania , Santos Aldina , Fick Lizette , Gicquel Brigitte , Jackson Mary , Quesniaux Valerie , Ryffel Bernhard 
Published: December 2004

ABSTRACT

We compared the growth levels and pathogenicities of the
Mycobacterium tuberculosis
MT103 clinical strain with those of the Δ
purC
mutant strain MYC1551, which is auxotrophic for purine in wild-type and gamma interferon receptor (IFN-γR)-deficient mice. The Δ
purC
strain MYC1551 grew initially in both wild-type and IFN-γR-deficient mice upon aerosol infection, but it grew much less than strain MT103 did. Despite the comparable bacterial burdens of the mice, IFN-γR-deficient mice succumbed to infection with Δ
purC
strain MYC1551 from necrotic pneumonia within 6 weeks of those infected with MT103. In conclusion, the Δ
purC
mutant MYC1551 displays reduced growth but retains pathogenicity. Therefore, the use of mutant strains of
M. tuberculosis
as live vaccines may not be recommended.
Neutralizing Antibodies Elicited by Immunization of Monkeys with DNA Plasmids and Recombinant Adenoviral Vectors Expressing Human Immunodeficiency Virus Type 1 Proteins
Authors: Mascola John R. , Sambor Anna , Beaudry Kristin , Santra Sampa , Welcher Brent , Louder Mark K. , VanCott Thomas C. , Huang Yue , Chakrabarti Bimal K. , Kong Wing-Pui , Yang Zhi-Yong , Xu Ling , Montefiori David C. , Nabel Gary J. , Letvin Norman L. 
Published: December 2004

ABSTRACT
Immunization with recombinant serotype 5 adenoviral (rAd5) vectors or a combination of DNA plasmid priming and rAd5 boosting is known to elicit potent immune responses. However, little data exist regarding these immunization strategies and the development of anti-human immunodeficiency virus type 1 (HIV-1) neutralizing antibodies. We used DNA plasmids and rAd5 vectors encoding the HIV-1 89.6P or chimeric HxB2/BaL envelope glycoprotein to immunize macaque monkeys. A single rAd5 immunization elicited anti-Env antibody responses, but there was little boosting with subsequent rAd5 immunizations. In contrast, rAd5 boosting of DNA-primed monkeys resulted in a rapid rise in antibody titers, including the development of anti-HIV-1 neutralizing antibodies. The potency and breadth of neutralization were evaluated by testing plasma against a panel of 14 clade B primary isolates. Moderate levels of plasma neutralizing activity were detected against about one-third of the viruses tested, and immunoglobulin G fractionation demonstrated that virus neutralization was antibody mediated. After a challenge with a chimeric simian-human immunodeficiency virus (SHIV89.6P), an anamnestic neutralizing antibody response was observed, although the breadth of the response was limited to the subset of viruses that were neutralized after the primary immunization. These data are the first detailed description of the anti-HIV-1 neutralizing antibody response in nonhuman primates elicited by DNA and rAd5 immunization. In addition to the well-established ability of DNA priming and rAd5 boosting to elicit potent anti-HIV-1 cellular immune responses, this immunization strategy elicits anti-HIV-1 neutralizing antibodies and therefore can be used to study novel Env immunogens designed to elicit more potent neutralizing antibodies.
Quantification of the Effects on Viral DNA Synthesis of Reverse Transcriptase Mutations Conferring Human Immunodeficiency Virus Type 1 Resistance to Nucleoside Analogues
Authors: Bouchonnet Francine , Dam Elisabeth , Mammano Fabrizio , de Soultrait Vaea , Henneré Gaëlle , Benech Henri , Clavel François , Hance Allan J. 
Published: December 2004

ABSTRACT
Human immunodeficiency virus type I (HIV-1) reverse transcriptase (RT) resistance mutations reduce the susceptibility of the virus to nucleoside analogues but may also impair viral DNA synthesis. To further characterize the effect of nucleoside analogue resistance mutations on the efficiency and kinetics of HIV-1 DNA synthesis and to evaluate the impact of the depletion of deoxynucleoside triphosphates (dNTP) on this process, DNA synthesis was evaluated by allowing DNA synthesis to proceed with natural HIV-1 templates and primers, either within permeabilized viral particles or in newly infected cells, and quantifying the products by real-time PCR. Three recombinant viruses derived from three pNL4-3 molecular clones expressing mutations associated with resistance to zidovudine: a clone expressing RT mutation M184V, a clone expressing mutations M41L plus T215Y (M41L+T215Y), and clinical isolate BV34 (carrying seven resistance mutations). Following infection of P4 cells, the BV34 mutant, but not viruses expressing the M184V mutation or M41L+T215Y, exhibited a defect in DNA synthesis. Importantly, however, for mutants carrying the M184V mutation or M41L+T215Y mutations, a defect could be detected by using target cells in which dATP pools had been reduced by pretreatment with hydroxyurea. Based on these observations, we developed a recombinant-virus assay to assess the effects of hydroxyurea pretreatment on infectivity of viruses carrying plasma-derived RT sequences from patients with nucleoside resistance. Using this assay, we found that many, but not all, viruses carrying RT resistance mutations display an increased sensitivity to hydroxyurea, suggesting that the impact of RT resistance mutations on viral replication may be more profound in cell populations characterized by smaller dNTP pools.
Does oral contraceptive use affect maximum force production in women?
Authors: Elliott K J , Cable N T , Reilly T 
Published: December 2004

Objective:To examine the effects of oral contraceptive use on maximum force production in young women.Methods:In the study, 21 female subjects (14 pill users and seven eumenorrheic controls) took part. All pill using subjects had been taking a combined, monophasic oral contraceptive pill for at least 6 months. Maximum dynamic and isometric leg strength, maximum isometric strength of the first dorsal interosseus (FDI) muscle, and plasma concentrations of oestradiol and progesterone were measured on days 7 and 14 of pill consumption and day 5 of pill withdrawal. The eumenorrheic group was tested (FDI strength and hormone concentrations) on days 2 and 21 of the menstrual cycle.Results:There were no significant changes in the concentration of endogenous oestradiol or progesterone or any measure of muscle strength between pill phases (p<0.05). The pill group did not significantly differ from the eumenorrheic group (p<0.05), despite a significant increase in the concentration of progesterone and oestradiol on day 21 of the menstrual cycle compared with day 2 of the menstrual cycle and pill consumption and withdrawal (p<0.05).Conclusions:These data suggest that oral contraceptive use does not significantly affect muscle strength. Moreover, oral contraceptive users were not stronger or weaker than their eumenorrheic counterparts.
Models and Managers: The Concept of a Decision Calculus
Authors: Little John D. C. 
Published: December 2004

(This article originally appeared in Management Science, April 1970, Volume 16, Number 8, pp. B-466–B-485, published by The Institute of Management Sciences.) A manager tries to put together the various resources under his control into an activity that achieves his objectives. A model of his operation can assist him but probably will not unless it meets certain requirements. A model that is to be used by a manager should be simple, robust, easy to control, adaptive, as complete as possible, and easy to communicate with. By simple is meant easy to understand; by robust, hard to get absurd answers from; by easy to control, that the user knows what input data would be required to produce desired output answers; adaptive means that the model can be adjusted as new information is acquired; completeness implies that important phenomena will be included even if they require judgmental estimates of their effect; and, finally, easy to communicate with means that the manager can quickly and easily change inputs and obtain and understand the outputs. Such a model consists of a set of numerical procedures for processing data and judgments to assist managerial decision making and so will be called a decision calculus. An example from marketing is described. It is an on-line model for use by product managers on advertising budgeting questions. The model is currently in trial use by several product managers.
Book Reviews
Authors: Katz Naomi , McCuckin Eric , Marie Small Linda , Simon Scott , Zimmer Richard 
Published: December 2004

Sister Jamaica:. Study of Women, Work and Household in Kingston. A. Lynn Bolles. Lanham, MD: University Press of America, 1996.ReORIENT: Global Economy in the Asian Age. Andre Gunder Frank. Berkeley: University of California Press, 1998.Laboring in the Fields of the Lord: Spanish Missions and Southeastern Indians. Jerald T. Milamch. Washington, DC: Smithsonian Institution Press, 1999.The Trading Crowd: An Ethnography of the Shanghai Stock Market. Ellen Hertz. Cambridge: Cambridge University Press, 1998.Analysing Community Work: Its Theory and Practice. Keith Popple. Buckingham, UK, and Philadelphia: Open University Press, 1995.
A concept for the clinical implementation of sentinel lymph node biopsy in patients with breast carcinoma with special regard to quality assurance
Authors: Kuehn Thorsten , Bembenek Andreas , Decker Thomas , Munz Dieter Ludwig , Sautter‐Bihl Marie‐Luise , Untch Michael , Wallwiener Diethelm ,   For the Consensus Committee of the German Society of Senology
Published: December 2004

AbstractThe development of standardized and reproducible clinical pathways is an important precondition for quality assurance in medicine, especially if a new method has not yet been ultimately validated. Sentinel lymph node biopsy (SLNB) is a widely accepted new surgical procedure in the treatment of early breast carcinoma. However, numerous steps of the method and details of the technique are not standardized and, thus, hamper quality assurance for SLNB. The German Society of Senology appointed an interdisciplinary consensus committee to work out guidelines for the standardized performance and quality‐assured implementation of SLNB on a nationwide, homogeneous standard. The committee consisted of surgeons, gynecologists, radiooncologists, nuclear physicians, oncologists, and pathologists. Relevant questions related to patient selection, lymphatic mapping, surgery, histopathologic work‐up, further local and systemic treatment decisions, patient information, training, and follow‐up were evaluated with respect to clinical evidence, objectivity, and reproducibility. Clinical pathways were developed on the basis of this analysis. Requirements to the performing institutions and surgeons were defined. Cancer 2005. © 2004 American Cancer Society.
Racial treatment trends in localized/regional prostate carcinoma: 1992–1999
Authors: Underwood Willie , Jackson James , Wei John T. , Dunn Rodney , Baker Edmond , DeMonner Sonya , Wood David P. 
Published: December 2004

AbstractBACKGROUNDAfrican‐American men have a greater incidence of and mortality from prostate carcinoma compared with white men, and they are less likely to receive definitive therapy (radical prostatectomy or external beam radiation therapy). During the 1990s, the use of brachytherapy increased; however, its influence on racial and ethnic prostate carcinoma treatment trends remains unclear. The objective of this study was to describe treatment trends over the period 1992–1999 for localized/regional prostate carcinoma among white, Hispanic, and African‐American men.METHODSUsing the Surveillance, Epidemiology, and End Results (SEER) registry data from 1992 through 1999, logistic regression models were used to determine whether the odds of receiving a specific treatment modality differed by racial and ethnic group and whether the differences changed over time when the models were adjusted for age, marital status, tumor grade, and SEER site (geography).RESULTSThe authors identified 142,340 men, including white men (81.6%), Hispanic men (6.4%), and African‐American men (12.0%). Racial and ethnic differences in the rates of use of androgen‐deprivation therapy/expectant management were noted; however, these differences appeared to lessen over time (P < 0.001). The rate of utilization of radical prostatectomy increased for Hispanic men, remained flat for African‐American men, and decreased for white men. The utilization of brachytherapy and combination therapy increased for all three groups; however, the greatest increase in utilization was among white men.CONCLUSIONSFurther research will be required to determine the patient‐level and provider‐level variables that influence racial and ethnic treatment differences in localized/regional prostate cancer. Cancer 2005. © 2005 American Cancer Society.
Multicenter determination of optimal interobserver agreement using the Fuhrman grading system for renal cell carcinoma
Authors: Lang Hervé , Lindner Véronique , de Fromont Marc , Molinié Vincent , Letourneux Hervé , Meyer Nicolas , Martin Mael , Jacqmin Didier 
Published: December 2004

AbstractBACKGROUNDThe Fuhrman system is the most widely used nuclear grading system for renal cell carcinoma (RCC). Although Fuhrman nuclear grade is widely accepted as a significant prognostic factor, its reproducibility, as reported in the limited number of series available in the literature, appears to be low.METHODSBetween 1980 and 1990, 255 cases of RCC (pT1–3bN0M0) were treated with radical nephrectomy at the Department of Urology, University Hospital, Strasbourg, France. In a retrospective multicenter study, 3 pathologists independently classified 241 of these 255 cases according to the Fuhrman grading system. The authors searched for optimal interobserver agreement by collapsing the grading system to a three‐tiered scheme and then to a two‐tiered scheme. In addition, overall survival curves were generated according to the classic four‐tiered scheme and also according to the best collapsed scheme. The kappa index was used to assess the level of agreement between each pair of observers, and the Cox model was used for multivariate survival analyses.RESULTSThe mean interobserver κ value was 0.22 (range, 0.09–0.36). The best concordance was obtained by collapsing to a system in which low‐grade (Grade 1–2) disease was compared with high‐grade (Grade 3–4) disease. Doing so improved the mean interobserver κ value to 0.44 (range, 0.32–0.55). Fuhrman grade was an independent prognostic factor for all 3 pathologists (P = 0.01, P < 0.0001, and P = 0.004, respectively), and nuclear grade continued to have independent prognostic value after the optimal collapsing algorithm was performed (P = 0.004, P = 0.0003, and P = 0.005).CONCLUSIONSCollapsing of the Fuhrman grading system to a two‐tiered scheme led to an improvement in interobserver agreement while preserving the independent prognostic value of nuclear grade. Cancer 2005. © 2004 American Cancer Society.