bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Vaccine Candidate
Vibrio cholerae
638 Is Protective against Cholera in Healthy Volunteers
Authors: García Luis , Jidy Manuel Díaz , García Hilda , Rodríguez Boris L. , Fernández Roberto , Año Gemma , Cedré Bárbara , Valmaseda Tania , Suzarte Edith , Ramírez Margarita , Pino Yadira , Campos Javier , Menéndez Jorge , Valera Rodrigo , González Daniel , González Irma , Pérez Oliver , Serrano Teresita , Lastre Miriam , Miralles Fernando , del Campo Judith , Maestre Jorge Luis , Pérez José Luis , Talavera Arturo , Pérez Antonio , Marrero Karen , Ledón Talena , Fando Rafael 
Published: April 2005

ABSTRACT

Vibrio cholerae
638 is a living candidate cholera vaccine strain attenuated by deletion of the CTXΦ prophage from C7258 (O1, El Tor Ogawa) and by insertion of the
Clostridium thermocellum
endoglucanase A gene into the hemagglutinin/protease coding sequence. This vaccine candidate was previously found to be well tolerated and immunogenic in volunteers. This article reports a randomized, double-blind, placebo-controlled trial conducted to test short-term protection conferred by 638 against subsequent
V. cholerae
infection and disease in volunteers in Cuba. A total of 45 subjects were enrolled and assigned to receive vaccine or placebo. The vaccine contained 10
9
CFU of freshly harvested 638 buffered with 1.3% NaHCO
3
, while the placebo was buffer alone. After vaccine but not after placebo intake, 96% of volunteers had at least a fourfold increase in vibriocidal antibody titers, and 50% showed a doubling of at least the lipopolysaccharide-specific immunoglobulin A titers in serum. At 1 month after vaccination, five volunteers from the vaccine group and five from the placebo group underwent an exploratory challenge study with 10
9
CFU of ΔCTXΦ attenuated mutant strain
V. cholerae
81. Only two volunteers from the vaccine group shed strain 81 in their feces, but none of them experienced diarrhea; in the placebo group, all volunteers excreted the challenge strain, and three had reactogenic diarrhea. An additional 12 vaccinees and 9 placebo recipients underwent challenge with 7 × 10
5
CFU of virulent strain
V. cholerae
3008 freshly harvested from a brain heart infusion agar plate and buffered with 1.3% NaHCO
3
. Three volunteers (25%) from the vaccine group and all from the placebo group shed the challenge agent in their feces. None of the 12 vaccinees but 7 volunteers from the placebo group had diarrhea, and 2 of the latter exhibited severe cholera (>5,000 g of diarrheal stool). These results indicate that at 1 month after ingestion of a single oral dose (10
9
CFU) of strain 638, volunteers remained protected against cholera infection and disease provoked by the wild-type challenge agent
V. cholerae
3008. We recommend that additional vaccine lots of 638 be prepared under good manufacturing practices for further evaluation.
Cytolethal Distending Toxin (CDT)-Negative
Campylobacter jejuni
Strains and Anti-CDT Neutralizing Antibodies Are Induced during Human Infection but Not during Colonization in Chickens
Authors: AbuOun Manal , Manning Georgina , Cawthraw Shaun A. , Ridley Anne , Ahmed If H. , Wassenaar Trudy M. , Newell Diane G. 
Published: April 2005

ABSTRACT

The cytolethal distending toxin (CDT) of
Campylobacter jejuni
was detectable, using an in vitro assay, in most but not all of 24 strains tested. The reason for the absence of toxin activity in these naturally occurring CDT-negative
C. jejuni
strains was then investigated at the genetic level. CDT is encoded by three highly conserved genes,
cdtA
,
-B
, and -
C
. In the CDT-negative strains, two types of mutation were identified. The CDT activities of
C. jejuni
strains possessing both types of mutation were successfully complemented with the functional genes of
C. jejuni
11168. The first type of mutation comprised a 667-bp deletion across
cdtA
and
cdtB
and considerable degeneration in the remainder of the
cdt
locus. Using a PCR technique to screen for this deletion, this mutation occurred in fewer than 3% of 147 human, veterinary, and environmental strains tested. The second type of mutation involved at least four nonsynonymous nucleotide changes, but only the replacement of proline with serine at CdtB position 95 was considered important for CDT activity. This was confirmed by site-directed mutagenesis. This type of mutation also occurred in fewer than 3% of strains as determined using a LightCycler biprobe assay. The detection of two CDT-negative clinical isolates raised questions about the role of CDT in some cases of human campylobacteriosis. To determine if anti-CDT antibodies are produced in human infection, a toxin neutralization assay was developed and validated using rabbit antisera. Pooled human sera from infected patients neutralized the toxin, indicating expression and immunogenicity during infection. However, no neutralizing antibodies were detected in colonized chickens despite the expression of CDT in the avian gut as indicated by reverse transcription-PCR.
Small-Molecule Inhibitors Specifically Targeting Type III Secretion
Authors: Nordfelth R. , Kauppi A. M. , Norberg H. A. , Wolf-Watz H. , Elofsson M. 
Published: April 2005

ABSTRACT

The type III secretion (TTS) system is used by several animal and plant pathogens to deliver effector proteins into the cytosol of the eukaryotic target cell as a strategy to evade the defense reactions elicited by the infected organism. The fact that these systems are highly homologous implies that novel antibacterial agents that chemically attenuate the pathogens via a specific interaction with the type III secretion mechanism can be identified. A number of small organic molecules having this potential have recently been identified (A. M. Kauppi, R. Nordfelth, H. Uvell, H. Wolf-Watz, and M. Elofsson, Chem. Biol. 10:241-249, 2003). Using different reporter gene constructs, we showed that compounds that belong to a class of acylated hydrazones of different salicylaldehydes target the TTS system of
Yersinia pseudotuberculosis
. One of these compounds, compound 1, was studied in detail and was found to specifically block Yop effector secretion under in vitro conditions by targeting the TTS system. In this respect the drug mimics the well-known effect of calcium on Yop secretion. In addition, compound 1 inhibits Yop effector translocation after infection of HeLa cells without affecting the eukaryotic cells or the bacteria. A HeLa cell model that mimics in vivo conditions showed that compound 1 chemically attenuates the pathogen to the advantage of the eukaryotic cell. Thus, our results show proof of concept, i.e., that small compounds targeting the TTS system can be identified, and they point to the possible use of TTS inhibitors as a novel class of antibacterial agents.
CD40 Signaling in Macrophages Induces Activity against an Intracellular Pathogen Independently of Gamma Interferon and Reactive Nitrogen Intermediates
Authors: Andrade Rosa M. , Portillo Jose-Andres C. , Wessendarp Matthew , Subauste Carlos S. 
Published: April 2005

ABSTRACTGamma interferon (IFN-γ) is the major inducer of classical activation of macrophages. Classically activated mouse macrophages acquire antimicrobial activity that is largely dependent on the production of reactive nitrogen intermediates. However, protection against important intracellular pathogens can take place in the absence of IFN-γ and nitric oxide synthase 2 (NOS2). UsingToxoplasma gondiias a model, we investigated if CD40 signaling generates mouse macrophages with effector function against an intracellular pathogen despite the absence of priming with IFN-γ and lack of production of reactive nitrogen intermediates. CD40-stimulated macrophages acquired anti-T. gondiiactivity that was not inhibited by a neutralizing anti-IFN-γ monoclonal antibody but was ablated by the neutralization of tumor necrosis factor alpha (TNF-α). Moreover, while the induction of anti-T. gondiiactivity in response to CD40 stimulation was unimpaired in macrophages from IFN-γ−/−mice, macrophages from TNF receptor 1/2−/−mice failed to respond to CD40 engagement. In contrast to IFN-γ-lipopolysaccharide, CD40 stimulation did not induce NOS2 expression and did not trigger production of reactive nitrogen intermediates. NeitherNG-monomethyl-l-arginine nor diphenyleneiodonium chloride affected the induction of anti-T. gondiiactivity in response to CD40. Finally, macrophages from NOS2−/−mice acquired anti-T. gondiiactivity in response to CD40 stimulation that was similar to that of macrophages from wild-type mice. These results demonstrate that CD40 induces the antimicrobial activity of macrophages against an intracellular pathogen despite the lack of two central features of classically activated macrophages: priming with IFN-γ and production of reactive nitrogen intermediates.
TheBartonella vinsoniisubsp.arupensisImmunodominant Surface Antigen BrpA Gene, Encoding a 382-Kilodalton Protein Composed of Repetitive Sequences, Is a Member of a Multigene Family Conserved amongBartonellaSpecies
Authors: Gilmore Robert D. , Bellville Travis M. , Sviat Steven L. , Frace Michael 
Published: April 2005

ABSTRACTBartonellaproteins that elicit an antibody response during an infection are poorly defined; therefore, to characterize antigens recognized by the host, aBartonellagenomic expression library was screened with serum from an infected mouse. This process led to the discovery of aBartonella vinsoniisubsp.arupensisgene encoding a 382-kDa protein, part of a gene family encoding large proteins, each containing multiple regions of repetitive segments. The genes were termedbrpAto-C(bartonellarepeatprotein) and bore significant similarity to genes encoding the BadA adhesin protein and members of the variably expressed outer membrane protein family of proteins fromBartonella henselaeandBartonella quintana, respectively.
A Hypothetical Protein of
Streptococcus mutans
Is Critical for Biofilm Formation
Authors: Brown Thomas A. , Ahn Sang-Joon , Frank Roslyn N. , Chen Yi-Ywan M. , Lemos José A. , Burne Robert A. 
Published: April 2005

ABSTRACT

Inactivation of the Smu0630 gene of
Streptococcus mutans
resulted in dramatic decreases in biofilm formation, regardless of the carbohydrate source. The Smu0630 protein contained numerous interesting features, including a possible signal sequence and two conserved regions of repeated sequences. Smu0630 may represent a potential target for novel therapeutics.
Requirement of MgtC for
Brucella suis
Intramacrophage Growth: a Potential Mechanism Shared by
Salmonella enterica
and
Mycobacterium tuberculosis
for Adaptation to a Low-Mg
2+
Environment
Authors: Lavigne Jean-Philippe , O'Callaghan David , Blanc-Potard Anne-Béatrice 
Published: April 2005

ABSTRACT

A
Brucella suis mgtC
mutant is defective for growth within macrophages and in low-Mg
2+
medium. These phenotypes are strikingly similar to those observed with
mgtC
mutants from
Salmonella enterica
and
Mycobacterium tuberculosis
, two other pathogens that proliferate within phagosomes. MgtC appears as a remarkable virulence factor that would have been acquired by distantly related intracellular pathogens to contribute to the adaptation to a low-Mg
2+
environment in the phagosome.
Interleukin-15 Enhances Innate and Adaptive Immune Responses to Blood-Stage Malaria Infection in Mice
Authors: Ing Rebecca , Gros Philippe , Stevenson Mary M. 
Published: April 2005

ABSTRACTCompared to C57BL/6 wild-type mice, interleukin-15−/−(IL-15−/−) mice showed delayed clearance ofPlasmodium chabaudiAS infection, lower type 1 cytokine production, impaired dendritic cell and NK cell functions, and lower titers of malaria-specific antibodies. Thus, IL-15 supports early control and timely resolution of blood-stage malaria through promotion of Th1-dependent innate and adaptive immune responses.
Conversion of
Staphylococcus epidermidis
Strains from Commensal to Invasive by Expression of the
ica
Locus Encoding Production of Biofilm Exopolysaccharide
Authors: Li Hualin , Xu Lin , Wang Jianping , Wen Yumei , Vuong Cuong , Otto Michael , Gao Qian 
Published: April 2005

ABSTRACT

To test if biofilm formation in
Staphylococcus epidermidis
is dependent on the polysaccharide intercellular adhesin, whose biosynthesis is driven by the
ica
locus, a plasmid containing the
ica
locus was transferred to three
ica
-negative strains. Using in vitro biofilm assays and a rat central venous catheter infection model, we confirmed the importance of the
ica
locus for biofilm production and pathogenesis of
S. epidermidis
.
Clinically diagnosed childhood asthma and follow-up of symptoms in a Swedish case control study
Authors: Roel Eduardo , Faresjö Åshild , Zetterström Olle , Trell Erik , Faresjö Tomas 
Published: April 2005

Abstract
Background
Childhood asthma has risen dramatically not only in the western societies and now forms a major and still increasing public health problem. The aims of this study were to follow up at the age of ten the patterns of asthma symptoms and associations among children with a clinically diagnosed asthma in a sizeable urban-rural community and to in compare them with demographic controls using a standardised questionnaire.

Methods
In a defined region in Sweden with a population of about 150 000 inhabitants, all children (n = 2 104) born in 1990 were recorded. At the age of seven all primary care and hospital records of the 1 752 children still living in the community were examined, and a group of children (n = 191) was defined with a well-documented and medically confirmed asthma diagnosis. At the age of ten, 86 % of these cases (n = 158) and controls (n = 171) completed an ISAAC questionnaire concerning asthma history, symptoms and related conditions.

Results
Different types of asthma symptoms were highly and significantly over-represented in the cases. Reported asthma heredity was significantly higher among the cases. No significant difference in reported allergic rhinitis or eczema as a child was found between cases and controls. No significant difference concerning social factors or environmental exposure was found between case and controls. Among the control group 4.7 % of the parents reported that their child actually had asthma. These are likely to be new asthma cases between the age of seven and ten and give an estimated asthma prevalence rate at the age of ten of 15.1 % in the studied cohort.

Conclusion
A combination of medical verified asthma diagnosis through medical records and the use of self-reported symptom through the ISAAC questionnaire seem to be valid and reliable measures to follow-up childhood asthma in the local community. The asthma prevalence at the age of ten in the studied birth cohort is considerably higher than previous reports for Sweden. Both the high prevalence figure and allowing the three-year lag phase for further settling of events in the community point at the complementary roles of both hospital and primary care in the comprehensive coverage and control of childhood asthma in the community.
Compulsory and recommended vaccination in Italy: evaluation of coverage and non-compliance between 1998-2002 in Northern Italy
Authors: Stampi Serena , Ricci Rita , Ruffilli Isa , Zanetti Franca 
Published: April 2005

Abstract

Background
Since vaccinations are an effective prevention tool for maintaining the health of society, the monitoring of immunization coverage allows us to identify areas where disease outbreaks are likely to occur, and possibly assist us in predicting future outbreaks. The aim of this study is the investigation of the coverage achieved for compulsory (diphtheria, tetanus, polio, hepatitis B,) and recommended (pertussis, Haemophilus influenzae, measles-mumps-rubella) vaccinations between 1998 and 2002 in the municipality of Bologna and the identification of the subjects not complying with compulsory and recommended vaccinations.

Methods
The statistics regarding vaccinal coverage were elaborated from the data supplied by the Bologna vaccinal registration system (1998–2000) and the IPV4 program (2001–2002). To calculate the coverage for compulsory vaccinations and cases of non-compliance reference was made to the protocol drawn up by the Emilia Romagna Regional Administration. The reasons for non-compliance were divided into various categories

Results
In Bologna the levels of immunization for the four compulsory vaccinations are satisfactory: over 95% children completed the vaccinal cycle, receiving the booster for anti-polio foreseen in their 3rd year and for anti-dyphteria, tetanus, pertussis at 6 years. The frequency of subjects with total non-compliance (i.e. those who have not begun any compulsory vaccinations by the age of one year) is generally higher in Bologna than in the region, with a slight increase in 2002 (2.52% and 1.06% in the city and the region respectively). The frequency of the anti-measles vaccination is higher than that of mumps and rubella, which means that the single vaccine, as opposed to the combined MMR (measles-mumps-rubella) was still being used in the period in question.
The most common reason for non compliance is objection of parents and is probably due to reduction of certain diseases or anxiety about the possible risks.

Conclusion
In Bologna the frequency of children aged 12 and 24 months who have achieved compulsory vaccination varied, in 2002, between 95% and 98%. As regards recommended vaccinations the percentage of coverage against Haemophilus influenzae is 93.3%, while the levels for measles, mumps and pertussis range from 84% to approx. 92%. Although these percentages are higher if compared to those obtained by other Italian regions, every effort should be made to strengthen the aspects that lead to a successful vaccinal strategy.
Relationship of patients' age to histopathological features of breast tumours in BRCA1 and BRCA2and mutation-negative breast cancer families
Authors: Eerola Hannaleena , Heikkilä Päivi , Tamminen Anitta , Aittomäki Kristiina , Blomqvist Carl , Nevanlinna Heli 
Published: April 2005

Abstract
Introduction
Our aim was to evaluate the relationship of patients' age to histopathological features of hereditary breast tumours in a series of breast cancer families not selected for age at diagnosis. In sporadic breast cancer, tumours from premenopausal patients have been shown to differ from those of postmenopausal patients, but this phenomenon has been little studied among familial patients.

Methods
Representative areas of all available breast cancer tissue specimens (n = 262) from 25 BRCA1, 20 BRCA2, and 74 non-BRCA1/2 breast cancer families were punched into a tissue microarray. Immunohistochemical staining of oestrogen receptor, progesterone receptor, ERBB2, and p53 as well as the histology and grade of tumours in these three groups of families were studied in different age groups and compared with each other.

Results
We found that only breast cancers from young (<50 years) BRCA1+ patients represent features documented as being typical of BRCA1-associated cancers, such as high tumour grade, negativity for oestrogen and progesterone receptors, and overexpression of p53. Among the BRCA2 families, the opposite was found, with a significantly higher frequency of tumours negative for oestrogen and progesterone receptors among the older patients than among the other groups, but no distinctive tumour characteristics among the younger BRCA2 patients.

Conclusion
Tumours of BRCA1 and BRCA2 carriers aged 50 years or more differed significantly from those of younger carriers. This difference may reflect different biological behaviour and pathways of tumour development among the older and the younger BRCA1 and BRCA2 patients, with impact also on prognosis and survival.
Treatment and partner notification outcomes for gonorrhoea: effect of ethnicity and gender
Authors: Apoola Ade , Mantella Isabelle , Wotton Mari , Radcliffe Keith 
Published: April 2005

We assessed if gender and ethnicity were associated with differences in the number of patients satisfactorily treated and number of partners successfully treated for genital gonococcal infection by reviewing 400 cases. There were no differences in the rates of satisfactory treatment of gonorrhoea between men and women and the different ethnic groups. There was no difference in satisfactory partner treatment rates by ethnic origin; however, men were less likely to have their contacts satisfactorily treated within 28 days of diagnosis (odds ratio=0.05, 95% confidence interval 0.3–0.7). This inequality may lead to difficulties in reducing the number of new gonorrhoea cases. More research is needed to find out why men behave differently from women regarding partner notification for genital gonorrhoea infection.
Sociodemography of genital co-infection with Neisseria gonorrhoeae and Chlamydia trachomatis in Coventry, UK
Authors: Das Satyajit , Sabin Caroline , Wade Abdel , Allan Sriskandab 
Published: April 2005

While genital co-infection with Neisseria gonorrhoeae and Chlamydia trachomatis in the same individual is relatively common, little is known about the characteristics of individuals co-infected with both pathogens. We describe the sociodemographic and geographic characteristics of those with genital co-infection with N. gonorrhoeae and C. trachomatis. We reviewed the case-notes of all patients presenting with co-infection between March 1989 and February 2000. Incidence rates were calculated for those aged 15–64 living in the 18 different electoral wards of the city and subjects were assigned a Townsend deprivation score based on residence. A total of 332 cases of co-infection were included over the study period (overall mean annual incidence rate 16.1 [95% confidence interval [CI] 9.9–22.3]/100,000). The infection rate was significantly higher in those of black ethnicity (rate: 82.6/105, relative rate 5.81, 95% CI [4.03–8.38], P=0.0001) than in those of other ethnicities. The highest incidence was noted in men aged 20–24 ( n=81, 45.6%) and in women aged 15–19 ( n=66, 45.2%) years, living in the most deprived area of the city. After controlling for year of diagnosis, those aged 25–64 years had significantly lower incidence rates (0.13 [0.10–0.17], P=0.0001, Poisson regression) than those aged <20 years. Increased incidence rates were also associated with high deprivation scores. There is a complex interaction between age, sex, ethnicity, geographic distribution, social deprivation and the risk of acquiring genital co-infection with N. gonorrhoeae and C. trachomatis. This study may help to identify the geographic areas of high incidence of sexually transmitted diseases in Coventry, and could be used as the baseline to measure the need for subsequent interventions.
How Do We Move Forward?
Authors: Eaton Kenneth 
Published: April 2005

In March 2004, a keynote national conference on the topic of ‘Reflection and Moving Forward’ was held in Manchester, as part of the national programme for primary dental care research and development (R&D). The conference was reported1 in the July 2004 edition of Primary Dental Care. It considered what had been achieved during the national research and development (R&D) programme, which had been targeted at primary dental care, and looked to the future. Abstracts of all the 47 completed projects, funded during the programme, were published at the time of the conference.2 The report in Primary Dental Care1 ended with the words, ‘it is hoped that the full proceedings of the day will be published later on this year’. On 25 January 2005, Professor Raman Bedi, Chief Dental Officer (CDO) for England, convened a meeting, held at the British Medical Association's London headquarters, to announce that the proceedings of the ‘Reflection and Moving Forward’ conference3 were now available and to discuss how to develop the capacity for research in primary oral healthcare in the future. Nineteen people ( Appendix 1) were invited to and attended the meeting. They included the Dean of the FGDP(UK) and the Editor of this journal. This article reports the meeting.