bluuebunny/crossref_metadata_2025_split huggingface dataset:
Direct Inhibition of T-Lymphocyte Activation by Anthrax Toxins In Vivo
Authors: Comer Jason E. , Chopra Ashok K. , Peterson Johnny W. , König Rolf 
Published: November 2005

ABSTRACTThe causative agent of anthrax,Bacillus anthracis, produces two toxins that contribute in part to its virulence. Lethal toxin is a metalloprotease that cleaves upstream mitogen-activated protein kinase kinases. Edema toxin is a calmodulin-dependent adenylate cyclase. Previous studies demonstrated that the anthrax toxins are important immunomodulators that promote immune evasion of the bacterium by suppressing activation of macrophages and dendritic cells. Here we showed that injection of sublethal doses of either lethal or edema toxin into mice directly inhibited the subsequent activation of T lymphocytes by T-cell receptor-mediated stimulation. Lymphocytes were isolated from toxin-injected mice after 1 or 4 days and stimulated with antibodies against CD3 and CD28. Treatment with either toxin inhibited the proliferation of T cells. Injection of lethal toxin also potently inhibited cytokine secretion by stimulated T cells. The effects of edema toxin on cytokine secretion were more complex and were dependent on the length of time between the injection of edema toxin and the isolation of lymphocytes. Treatment with lethal toxin blocked multiple kinase signaling pathways important for T-cell receptor-mediated activation of T cells. Phosphorylation of the extracellular signal-regulated kinase and the stress-activated kinase p38 was significantly decreased. In addition, phosphorylation of the serine/threonine kinase AKT and of glycogen synthase kinase 3 was inhibited in T cells from lethal toxin-injected mice. Thus, anthrax toxins directly act on T lymphocytes in a mouse model. These findings are important for future anthrax vaccine development and treatment.
Pseudomonas aeruginosa
Acquires Biofilm-Like Properties within Airway Epithelial Cells
Authors: Garcia-Medina Raquel , Dunne W. Michael , Singh Pradeep K. , Brody Steven L. 
Published: November 2005

ABSTRACT

Pseudomonas aeruginosa
can notably cause both acute and chronic infection. While several virulence factors are implicated in the acute phase of infection, advances in understanding bacterial pathogenesis suggest that chronic
P. aeruginosa
infection is related to biofilm formation. However, the relationship between these two forms of disease is not well understood. Accumulating evidence indicates that, during acute infection,
P. aeruginosa
enters epithelial cells, a process viewed as either a host-mediated defense response or a pathogenic mechanism to avoid host-mediated killing. We investigated the possibility that epithelial cell entry during early
P. aeruginosa-
epithelial cell contact favors bacterial survival and is linked to chronic infection. Using electron microscopy and confocal microscopy to analyze primary culture airway epithelial cells infected with
P. aeruginosa
, we found that epithelial cells developed pod-like clusters of intracellular bacteria with regional variation in protein expression. Extracellular gentamicin added to the medium after acute infection led to the persistence of intracellular
P. aeruginosa
for at least 3 days. Importantly, compared to bacterial culture under planktonic conditions, the intracellular bacteria were insensitive to growth inhibition or killing by antibiotics that were capable of intraepithelial cell penetration. These findings suggest that
P. aeruginosa
can use airway epithelial cells as a sanctuary for persistence and develop a reversible antibiotic resistance phenotype characteristic of biofilm physiology that can contribute to development of chronic infection.
Whole-Genome Analyses of Speciation Events in Pathogenic Brucellae
Authors: Chain Patrick S. G. , Comerci Diego J. , Tolmasky Marcelo E. , Larimer Frank W. , Malfatti Stephanie A. , Vergez Lisa M. , Aguero Fernan , Land Miriam L. , Ugalde Rodolfo A. , Garcia Emilio 
Published: November 2005

ABSTRACT

Despite their high DNA identity and a proposal to group classical
Brucella
species as biovars of
Brucella melitensis
, the commonly recognized
Brucella
species can be distinguished by distinct biochemical and fatty acid characters, as well as by a marked host range (e.g.,
Brucella suis
for swine,
B. melitensis
for sheep and goats, and
Brucella abortus
for cattle). Here we present the genome of
B. abortus
2308, the virulent prototype biovar 1 strain, and its comparison to the two other human pathogenic
Brucella
species and to
B. abortus
field isolate 9-941. The global distribution of pseudogenes, deletions, and insertions supports previous indications that
B. abortus
and
B. melitensis
share a common ancestor that diverged from
B. suis
. With the exception of a dozen genes, the genetic complements of both
B. abortus
strains are identical, whereas the three species differ in gene content and pseudogenes. The pattern of species-specific gene inactivations affecting transcriptional regulators and outer membrane proteins suggests that these inactivations may play an important role in the establishment of host specificity and may have been a primary driver of speciation in the genus
Brucella
. Despite being nonmotile, the brucellae contain flagellum gene clusters and display species-specific flagellar gene inactivations, which lead to the putative generation of different versions of flagellum-derived structures and may contribute to differences in host specificity and virulence. Metabolic changes such as the lack of complete metabolic pathways for the synthesis of numerous compounds (e.g., glycogen, biotin, NAD, and choline) are consistent with adaptation of brucellae to an intracellular life-style.
Passive Protection against Anthrax by Using a High-Affinity Antitoxin Antibody Fragment Lacking an Fc Region
Authors: Mabry Robert , Rani Mridula , Geiger Robert , Hubbard Gene B. , Carrion Ricardo , Brasky Kathleen , Patterson Jean L. , Georgiou George , Iverson B. L. 
Published: November 2005

ABSTRACT

Passive immunization has been successfully employed for protection against bacterial and viral infections for over 100 years. Immunoglobulin Fc regions play a critical role in the clearance of bacterial pathogens by mediating antibody-dependent and complement-dependent cytotoxicity. Here we show that antibody fragments engineered to recognize the protective antigen component of the
B. anthracis
exotoxin with high affinity and conjugated to polyethylene glycol (PEG) for prolonged circulation half-life confer significant protection against inhalation anthrax despite their lack of Fc regions. The speed and lower manufacturing cost of bacterially expressed PEGylated antibody fragments could provide decisive advantages for anthrax prophylaxis. Importantly, our results suggest that PEGylated antibody fragments may represent a unique approach for mounting a rapid therapeutic response to emerging pathogen infections.
Reduction of Cell Surface Glycosylphosphatidylinositol Conjugates inEntamoeba histolyticaby Antisense Blocking ofE. histolyticaGlcNAc-Phosphatidylinositol Deacetylase Expression: Effect on Cell Proliferation, Endocytosis, and Adhesion to Target Cells
Authors: Vats Divya , Vishwakarma Ram A. , Bhattacharya Sudha , Bhattacharya Alok 
Published: November 2005

ABSTRACTGlycosylphosphatidylinositol (GPI)-anchored molecules such as cell surface Gal/GalNAc lectin and proteophosphoglycans of the protozoan parasiteEntamoeba histolyticaare thought to be involved in pathogenesis. Here, we report the identification of genes that may be involved in the GPI biosynthetic pathway ofE. histolyticaby use of bioinformatic tools applied to the recently published genome sequence. Of the genes identified, one of the early genes, GlcNAc-phosphatidylinositol deacetylase (PIG-L), was partially characterized. Cell lines deficient inE. histolyticaPIG-L (EhPL-AS) or overproducing it (EhPL-S) were generated by expressing the gene in the antisense or sense orientation, respectively, in a tetracycline-inducible system. The overexpressing cells showed higher EhPIG-L activity and increased production of GlcN-PI. Conversely, cells expressing the antisense RNA displayed reduced GlcN-PI production. The total number of GPI-containing molecules was also reduced in these cells, as demonstrated by Alexa 488 fluorescently labeled proaerolysin labeling. The distribution of GPI-linked PPG and Gal/GalNAc lectin was altered in the tetracycline-induced EhPL-AS cell lines. Further, the antisense-blocked cells showed 36% suppression of cell growth, 50 to 60% inhibition of fluid phase endocytosis, and about 50% inhibition of adhesion to target cells. Therefore, our data suggest the importance of GPI anchors in regulating some of the events in amoebic pathogenesis. They also demonstrated the use of antisense RNA-mediated inhibition of GPI biosynthetic enzymes as an approach to decrease the amount of GPI conjugates inE. histolytica.
Intrapulmonary, Adenovirus-Mediated Overexpression of KARAP/DAP12 Enhances Fungal Clearance during Invasive Aspergillosis
Authors: Carpenter Kristin J. , Buckland Karen F. , Xing Zhou , Hogaboam Cory M. 
Published: November 2005

ABSTRACTHerein, we report that the intrapulmonary delivery of an adenovirus vector expressing KARAP/DAP12, an adaptor protein expressed in granulocytes and mononuclear cells, enhanced fungal clearance during experimental invasive pulmonary aspergillosis in neutropenic mice.
Clostridium perfringens
Enterotoxin Damages the Human Intestine In Vitro
Authors: Fernández Miyakawa M. E. , Pistone Creydt V. , Uzal F. A. , McClane B. A. , Ibarra C. 
Published: November 2005

ABSTRACT

In vitro,
Clostridium perfringens
enterotoxin (CPE) binds to human ileal epithelium and induces morphological damage concurrently with reduced short-circuit current, transepithelial resistance, and net water absorption. CPE also binds to the human colon in vitro but causes only slight morphological and transport changes that are not statistically significant.
High Susceptibility of Human Dendritic Cells to Invasion by the Intracellular PathogensBrucella suis, B. abortus, andB. melitensis
Authors: Billard Elisabeth , Cazevieille Chantal , Dornand Jacques , Gross Antoine 
Published: November 2005

ABSTRACTBacteria from theBrucellagenus are able to survive and proliferate within macrophages. Because they are phylogenetically closely related to macrophages, myeloid dendritic cells (DCs) constitute potential targets forBrucellabacteria. Here we report that DCs display a great susceptibility toBrucellainfection. Therefore, DCs might serve as a reservoir and be important for the development ofBrucellabacteria within their host.
Eosinophils, but Not Eosinophil Peroxidase or Major Basic Protein, Are Important for Host Protection in ExperimentalBrugia pahangiInfection
Authors: Ramalingam Thirumalai , Porte Patricia , Lee James , Rajan T. V. 
Published: November 2005

ABSTRACTThe attenuation of eosinophilia by the administration of monoclonal antibodies to CCR3 consistently correlates with impairment in worm elimination following primary intraperitonealBrugia pahangiinfections in mice. Host protection was unimpaired in mice deficient in eosinophil peroxidase (EPO) or major basic protein 1 (MBP-1), suggesting that eosinophils are essential in host protection but that neither EPO nor MBP-1 alone is.
Azurin of Pathogenic
Neisseria
spp. Is Involved in Defense against Hydrogen Peroxide and Survival within Cervical Epithelial Cells
Authors: Wu Hsing-Ju , Seib Kate L. , Edwards Jennifer L. , Apicella Michael A. , McEwan Alastair G. , Jennings Michael P. 
Published: November 2005

ABSTRACT

Laz, a lipid-modified azurin of the human pathogens
Neisseria gonorrhoeae
and
Neisseria meningitidis
, is involved in defense against oxidative stress and copper toxicity;
laz
mutant strains are hypersensitive to hydrogen peroxide and copper. The
N. gonorrhoeae laz
mutant also has decreased survival in an ex vivo primary human ectocervical epithelial assay.
Different
Helicobacter hepaticus
Strains with Variable Genomic Content Induce Various Degrees of Hepatitis
Authors: Boutin Samuel R. , Shen Zeli , Rogers Arlin B. , Feng Yan , Ge Zhongming , Xu Sandy , Sterzenbach Torsten , Josenhans Christine , Schauer David B. , Suerbaum Sebastian , Fox James G. 
Published: November 2005

ABSTRACT

A 70-kb genomic island (HHGI1) in
Helicobacter hepaticus
strain ATCC 51449 is a putative pathogenicity island (PAI). To determine the in vivo relevance of this PAI, we inoculated A/JCr mice with one of three strains of
H. hepaticus
: type strain Hh3B1, which contains the complete PAI, and strains HhNET and HhG, which lack all or large parts of HHGI1, respectively. Mice infected with HhG and HhNET developed less-severe hepatitis than male A/JCr mice infected with Hh3B1.
Associations between ambient, personal, and indoor exposure to fine particulate matter constituents in Dutch and Finnish panels of cardiovascular patients
Authors: Janssen N A H , Lanki T , Hoek G , Vallius M , de Hartog J J , Van Grieken R , Pekkanen J , Brunekreef B 
Published: November 2005

Aims:To assess the relation between ambient, indoor, and personal levels of PM2.5and its elemental composition for elderly subjects with cardiovascular disease.Methods:In the framework of a European Union funded study, panel studies were conducted in Amsterdam, the Netherlands and Helsinki, Finland. Outdoor PM2.5concentrations were measured at a fixed site. Each subject’s indoor and personal PM2.5exposure was measured biweekly for six months, during the 24 hour period preceding intensive health measurements. The absorbance of PM2.5filters was measured as a marker for diesel exhaust. The elemental content of more than 50% of the personal and indoor samples and all corresponding outdoor samples was measured using energy dispersivexray fluorescence.Results:For Amsterdam and Helsinki respectively, a total of 225 and 238 personal, and 220 and 233 indoor measurements, were analysed from 36 and 46 subjects. For most elements, personal and indoor concentrations were lower than and highly correlated with outdoor concentrations. The highest correlations (medianr>0.9) were found for sulfur and particle absorbance, which both represent fine mode particles from outdoor origin. Low correlations were observed for elements that represent the coarser part of the PM2.5particles (Ca, Cu, Si, Cl).Conclusions:The findings of this study provide support for using fixed site measurements as a measure of exposure to particulate matter in time series studies linking the day to day variation in particulate matter to the day to day variation in health endpoints, especially for components of particulate matter that are generally associated with fine particles and have few indoor sources. The high correlation for absorbance of PM2.5documents that this applies to particulate matter from combustion sources, such as diesel vehicles, as well.
An updated study of mortality among North American synthetic rubber industry workers
Authors: Sathiakumar N , Graff J , Macaluso M , Maldonado G , Matthews R , Delzell E 
Published: November 2005

Aim:This study evaluated the mortality experience of workers from the styrene-butadiene industry.Methods:The authors added seven years of follow up to a previous investigation of mortality among 17 924 men employed in the North American synthetic rubber industry. Analyses used the standardised mortality ratios (SMRs) to compare styrene-butadiene rubber workers’ cause specific mortality (1943–98) with those of the United States and the Ontario general populations.Results:Overall, the observed/expected numbers of deaths were 6237/7242 for all causes (SMR = 86, 95% CI 84 to 88) and 1608/1741 for all cancers combined (SMR = 92, 95% CI 88 to 97), 71/61 for leukaemia, 53/53 for non-Hodgkin’s lymphoma, and 26/27 for multiple myeloma. The 16% leukaemia increase was concentrated in hourly paid subjects with 20–29 years since hire and 10 or more years of employment in the industry (19/7.4, SMR = 258, 95% CI 156 to 403) and in subjects employed in polymerisation (18/8.8, SMR = 204, 95% CI 121 to 322), maintenance labour (15/7.4, SMR = 326, 95% CI 178 to 456), and laboratory operations (14/4.3, SMR = 326, 95% CI 178–546).Conclusion:The study found that some subgroups of synthetic rubber workers had an excess of mortality from leukaemia that was not limited to a particular form of leukaemia. Uncertainty remains about the specific agent(s) that might be responsible for the observed excesses and about the role of unidentified confounding factors. The study did not find any clear relation between employment in the industry and other forms of lymphohaematopoietic cancer. Some subgroups of subjects had more than expected deaths from colorectal and prostate cancers. These increases did not appear to be related to occupational exposure in the industry.
Incidence by occupation and industry of acute work related respiratory diseases in the UK, 1992–2001
Authors: McDonald J C , Chen Y , Zekveld C , Cherry N M 
Published: November 2005

Aims:To summarise incidence rates and epidemiological characteristics of new cases of work related respiratory disease reported by specialist physicians in thoracic and occupational medicine, with particular reference to occupation, industry, and causal agents for asthma, inhalation accidents, and allergic alveolitis.Methods:Cases reported 1992–2001 to the SWORD and OPRA national surveillance schemes, in which almost all UK chest and occupational physicians participate, were analysed by age, sex, cause, occupation, and industry, with incidence rates calculated against appropriate denominators.Results:Excluding diseases of long latency, infrequently seen by occupational physicians, the distribution of diagnoses in the two specialties was similar, but with rates generally much higher in occupational than chest physicians. Occupational asthma was responsible for about 25% of cases overall, affecting mainly craft related occupations and machinists, and most often attributed to isocyanates, metals, grains, wood dusts, solders, and welding fume. These same occupations were those at highest risk from inhalation injuries, most frequently caused by irritant gases, vapours, and fume. Among medical technicians and nurses, however, glutaraldehyde and latex were the main causes of occupational asthma. Allergic alveolitis was seldom reported, with almost all cases in agriculture, forestry, and fishing.Conclusion:During the 10 year period studied, there were few changes in level of reported incidence, apart from some decline in occupational asthma and inhalation injuries. These results and their implications should be distinguished from much higher estimates of asthma made worse by work derived from population surveys, based on prevalence rather than incidence, and self-reported symptoms rather than diagnoses made by specialist physicians. Even so, the reported incidence of new cases of acute respiratory illness caused by work remains substantial.
Prevention of work related eye injuries: long term assessment of the effectiveness of a multicomponent intervention among metal workers
Authors: Mancini G , Baldasseroni A , Laffi G , Curti S , Mattioli S , Violante F S 
Published: November 2005

Background:Systematic assessments of the effectiveness of interventions to prevent work related eye injuries are needed.Aim:To investigate the long term effectiveness of a multicomponent prevention campaign.Methods:The campaign (conducted in collaboration with the local Employers’ Association and Trade Unions) targeted all 237 metal-ware factories in the district of Imola, Italy. Based on preliminary inspections, the main intervention included distribution to all factories of specific educational brochures and broadcasting/publication of television/radio programmes and local newspaper articles containing expert advice on the subject. This was followed by a four year “post-intervention reinforcement” period of unannounced official inspections. Main outcome measures analysed were eye injury rates (versus non-eye injury rates) among metal workers during “pre-intervention” (1988–90), “peri-intervention” (1991–92), “post-intervention reinforcement” (1993–96), “late post-intervention” (1997–2000), and “very late post-intervention” (2001–03) periods with respect to two comparison sectors (construction and wood/ceramics).Results:A Poisson regression in which the eye injury rates were modelled for each sector, period, and interaction, adjusting for non-eye injury rates, was chosen. The periods did not by themselves determine an overall reduction in eye injuries. The period/sector interaction terms were related to significant reductions for the metal sector when crossed with the “post-intervention reinforcement” (IRR = 0.77, 95% CI 0.61 to 0.97; % decline = 23.4), the “late post-intervention” (IRR = 0.63, 95% CI 0.50 to 0.79; % decline = 37.4), and the “very late post-intervention” (IRR =  0.58, 95% CI 0.43 to 0.77; % decline = 42.4) periods, suggesting a sustained reduction in eye injury risk following the main intervention.Conclusion:Results suggest that a carefully coordinated, extensive, multicomponent intervention can lead to lasting reductions in the burden of eye injuries.
Long driving time is associated with haematological markers of increased cardiovascular risk in taxi drivers
Authors: Chen J-C , Chen Y-J , Chang W P , Christiani D C 
Published: November 2005

Aims:To examine the association between driving time and changes in haematological markers of increased risks for cardiovascular diseases (CVD).Methods:The authors conducted a cross sectional analysis of baseline data from the Taxi Drivers’ Health Study cohort in Taipei, Taiwan. They retrieved information on comorbidity, laboratory tests, age, and anthropometric measures from medical records of 1157 subjects (mean age 44.6 (SD 8.6) years). Whole blood cell (WBC) count was used as the primary haematological marker for increased CVD risk, and platelet count and haematocrit as the secondary markers. Standardised questionnaires were implemented to collect information on demographics, lifestyle, work related physical and psychosocial factors, and driving time profiles. Multiple regression was used to estimate the adjusted effects of driving time on three haematological markers.Results:The mean measured hematological marker was 6656 (SD 1656) cells ×106/l for WBC, 47.2 (SD 3.5) % for hematocrit, and 243 (SD 52) cells ×109/l for platelets. The driving time was 264 (SD 76) hours/month. Compared with drivers who drove ⩽208 hours/month (1st quartile cut off), drivers who drove >208 hours/month had a higher WBC count (by 317 ×106/l; 95% CI 99 to 535), haematocrit (by 0.8%; 95% CI 0.3 to 1.2), and platelets (7.9 ×109/l; 95% CI 1.0 to 14.8). After adjusting for conventional CVD risk factors (age, sex, smoking, hypertension, diabetes, and hypercholesterolaemia), obesity, alcohol drinking, regular exercise, and sociodemographics (education, marital status, income, and so on), long driving time was still associated with significant increases in WBC and platelets, whereas the effect on haematocrit was diminished and became statistically non-significant. Additional controls for physical workload, self-perceived job stress, and job dissatisfaction did not alter the associations with increased WBC and platelets.Conclusions:Longitudinal studies are needed to confirm the observed cross sectional association and to further examine the specific occupational exposures accountable for the association between driving time and haematological markers of systemic inflammation and haemostatic alteration.