Search tips
Search criteria

Results 1-6 (6)

Clipboard (0)

Select a Filter Below

Year of Publication
Document Types
author:("Le fevr, A")
1.  Characterization and Interlaboratory Comparison of a Gene Expression Signature for Differentiating Genotoxic Mechanisms 
Toxicological Sciences  2009;110(2):341-352.
The genotoxicity testing battery is highly sensitive for detection of chemical carcinogens. However, it features a low specificity and provides only limited mechanistic information required for risk assessment of positive findings. This is especially important in case of positive findings in the in vitro chromosome damage assays, because chromosome damage may be also induced secondarily to cell death. An increasing body of evidence indicates that toxicogenomic analysis of cellular stress responses provides an insight into mechanisms of action of genotoxicants. To evaluate the utility of such a toxicogenomic analysis we evaluated gene expression profiles of TK6 cells treated with four model genotoxic agents using a targeted high density real-time PCR approach in a multilaboratory project coordinated by the Health and Environmental Sciences Institute Committee on the Application of Genomics in Mechanism-based Risk Assessment. We show that this gene profiling technology produced reproducible data across laboratories allowing us to conclude that expression analysis of a relevant gene set is capable of distinguishing compounds that cause DNA adducts or double strand breaks from those that interfere with mitotic spindle function or that cause chromosome damage as a consequence of cytotoxicity. Furthermore, our data suggest that the gene expression profiles at early time points are most likely to provide information relevant to mechanisms of genotoxic damage and that larger gene expression arrays will likely provide richer information for differentiating molecular mechanisms of action of genotoxicants. Although more compounds need to be tested to identify a robust molecular signature, this study confirms the potential of toxicogenomic analysis for investigation of genotoxic mechanisms.
PMCID: PMC2734310  PMID: 19465456
gene expression; genetic toxicology; risk assessment
2.  Infant morbidity in an Indian slum birth cohort 
Archives of disease in childhood  2007;93(6):479-484.
To establish incidence rates, clinic referrals, hospitalisations, mortality rates and baseline determinants of morbidity among infants in an Indian slum.
A community-based birth cohort with twice-weekly surveillance.
Vellore, South India.
452 newborns recruited over 18 months, followed through infancy.
Main outcome measures
Incidence rates of gastrointestinal illness, respiratory illness, undifferentiated fever, other infections and non-infectious morbidity; rates of community-based diagnoses, clinic visits and hospitalisation; and rate ratios of baseline factors for morbidity.
Infants experienced 12 episodes (95% confidence interval (CI) 11 to 13) of illness, spending about one fifth of their infancy with an illness. Respiratory and gastrointestinal symptoms were most common with incidence rates (95% CI) of 7.4 (6.9 to 7.9) and 3.6 (3.3 to 3.9) episodes per child-year. Factors independently associated with a higher incidence of respiratory and gastrointestinal illness were age (3-5 months), male sex, cold/wet season and household involved in beedi work. The rate (95% CI) of hospitalisation, mainly for respiratory and gastrointestinal illness, was 0.28 (0.22 to 0.35) per child-year.
The morbidity burden due to respiratory and gastrointestinal illness is high in a South Indian urban slum, with children ill for approximately one fifth of infancy, mainly with respiratory and gastrointestinal illnesses. The risk factors identified were younger age, male sex, cold/wet season and household involvement in beedi work.
PMCID: PMC2682775  PMID: 17916587
3.  Neonatal Infection with G10P[11] Rotavirus Did Not Confer Protection against Subsequent Rotavirus Infection in a Community Cohort in Vellore, South India 
The Journal of infectious diseases  2007;195(5):625-632.
Various observational studies have suggested that neonatal rotavirus infection confers protection against diarrhea due to subsequent rotavirus infection. We examined the incidence of rotavirus infection and diarrhea during the first 2 years of life among children infected with the G10P[11] rotavirus strain during the neonatal period and those not infected with rotavirus.
Children were recruited at birth and were followed up at least twice weekly. Stool samples, collected every 2 weeks for surveillance and at each episode of diarrhea, were screened by enzyme-linked immunosorbent assay and were genotyped by polymerase chain reaction.
Among 33 children infected neonatally with G10P[11] and 300 children not infected with rotavirus, there was no significant difference in the rates of rotavirus-positive diarrhea (rate ratio [RR], 1.05 [95% confidence interval {CI}, 0.61–1.79]), moderate or severe rotavirus-positive diarrhea (RR, 1.42 [95% CI, 0.73–2.78]), or asymptomatic rotavirus shedding (RR, 1.25 [95% CI, 0.85–1.83]).
Neonatal G10P[11] infection with a strain resembling a vaccine candidate did not confer protection against subsequent rotavirus infection or diarrhea of any severity in this setting.
PMCID: PMC2483790  PMID: 17262703
4.  Geographic Information Systems and Genotyping in Identification of Rotavirus G12 Infections in Residents of an Urban Slum with Subsequent Detection in Hospitalized Children: Emergence of G12 Genotype in South India▿  
Journal of Clinical Microbiology  2006;45(2):432-437.
Rotavirus infections by G12 strains in several countries have recently been described. In this study, we report the emergence of G12 strains in south India. Fourteen cases of G12 infection were identified between June and September 2005. G12 was seen in combination with P[6], P[8], or nontypeable P type. Nine cases, including five symptomatic infections and four asymptomatic infections, were identified as part of routine surveillance for rotavirus infections in a birth cohort in the community between June and July 2005. Significant temporal and time-space clustering of eight of these cases represents a possible recent introduction of a new rotavirus VP7 genotype. Previous rotavirus infections had been documented for six of the nine children in the community. In the following 2 months, five cases of G12 infection were identified among children presenting to a referral hospital with diarrhea. This is the first description of symptomatic and asymptomatic G12 infections in children in the community. The detection of G12 strains from different parts of the world in recent years suggests the possibility of its emergence as an important global genotype. Monitoring of cocirculating rotavirus strains and detection of emerging strains is important in the context of the availability of rotavirus vaccines.
PMCID: PMC1829045  PMID: 17135437
5.  Herd-level risk factors associated with tuberculosis breakdowns among cattle herds in England before the 2001 foot‐and‐mouth disease epidemic 
Biology Letters  2005;1(1):53-56.
A case–control study of the factors associated with the risk of a bovine tuberculosis (TB) breakdown in cattle herds was undertaken within the randomized badger culling trial (RBCT). TB breakdowns occurring prior to the 2001 foot-and-mouth disease epidemic in three RBCT triplets were eligible to be cases; controls were selected from the same RBCT area. Data from 151 case farms and 117 control farms were analysed using logistic regression. The strongest factors associated with an increased TB risk were movement of cattle onto the farm from markets or farm sales, operating a farm over multiple premises and the use of either covered yard or ‘other’ housing types. Spreading artificial fertilizers or farmyard manure on grazing land were both associated with decreased risk. These first case–control results from the RBCT will be followed by similar analyses as more data become available.
PMCID: PMC1629052  PMID: 17148126
bovine tuberculosis; case–control study; cattle movement; randomized badger culling trial; TB99
6.  Aerobic exercise in the adjunctive treatment of depression: a randomized controlled trial. 
Two clinical trials have been conducted in a sample of depressed patients to determine whether the addition of an aerobic exercise programme to their usual treatment improved outcome after 12 weeks. In the first trial, an aerobic exercise group had a superior outcome compared with a control group in terms of trait anxiety and a standard psychiatric interview. A second trial was then conducted to compare an aerobic exercise programme with low intensity exercise. Both groups showed improvement but there were no significant differences between the groups. In neither trial was there any correlation between the extent of change in the subjects' physical fitness due to aerobic exercise and the extent of the improvement of psychiatric scores.
PMCID: PMC1293641  PMID: 1433121

Results 1-6 (6)