Search

Purpose: Use of antiepileptic drugs in pregnancy is associated with congenital malformations and developmental delay. Previous studies have suggested that women who have had one child with a congenital malformation are at increased risk of having other children with malformations. We sought to confirm the magnitude of risk in a large cohort drawn from the United Kingdom Epilepsy and Pregnancy Register. Methods: The United Kingdom Epilepsy and Pregnancy Register is a prospective, observational registration and follow-up study set up to determine the relative safety of antiepileptic drugs in pregnancy. We have extracted data for those women who prospectively registered more than one pregnancy and calculated the recurrence risks for fetal malformations. Key Findings: Outcome data were available for 1,534 pregnancies born to 719 mothers. For women whose first child had a congenital malformation there was a 16.8% risk of having another child with a congenital malformation, compared with 9.8% for women whose first child did not have a malformation (relative risk 1.73, 95% confidence interval [CI] 1.01-2.96). The risk for recurrence was 50% for women who had had two previous children with a congenital malformation. There was a trend toward a higher risk for recurrent malformations in pregnancies exposed to valproate (21.9%, relative risk 1.47, 95% CI 0.68-3.20) and topiramate (50%, relative risk 4.50, 95% CI 0.97-20.82), but not for other drugs such as carbamazepine and lamotrigine. Recurrence risks were also higher for pregnancies exposed to polytherapy regimens and for those where the dose of antiepileptic drug treatment had been increased after the first pregnancy. Significance: Women who have had a child with a malformation are at increased risk of having other children with malformations. This is in keeping with previous reports that have suggested that genetic influences may be one of the factors determining the teratogenic risk of antiepileptic drugs. [ABSTRACT FROM AUTHOR]

The article discusses the portrayal of writers within children's literature. The authors analyzed the books by searching for themes, keywords, recurring motifs, and purposeful content analysis which means comparing, contrasting and characterizing data, according to the article. Why the story's character writes is explored. The different ways characters benefit from their writing include helping them to cope with life experiences, documenting their experience, building relationships and validating their identity as a writer. What effect the character's writing had on an audience was analyzed.

The inhA and kasA genes of Mycobacterium tuberculosis have each been proposed to encode the primary target of the antibiotic isoniazid (INH). Previous studies investigating whether overexpressed inhA or kasA could confer resistance to INH yielded disparate results. In this work, multicopy plasmids expressing either inhA or kasA genes were transformed into M. smegmatis, M. bovis BCG and three different M. tuberculosis strains. The resulting transformants, as well as previously published M. tuberculosis strains with multicopy inhA or kasAB plasmids, were tested for their resistance to INH, ethionamide (ETH) or thiolactomycin (TLM). Mycobacteria containing inhA plasmids uniformly exhibited 20-fold or greater increased resistance to INH and 10-fold or greater increased resistance to ETH. In contrast, the kasA plasmid conferred no increased resistance to INH or ETH in any of the five strains, but it did confer resistance to thiolactomycin, a known KasA inhibitor. INH is known to increase the expression of kasA in INHsusceptible M. tuberculosis strains. Using molecular beacons, quantified inhA and kasA mRNA levels showed that increased inhA mRNA levels correlated with INH resistance, whereas kasA mRNA levels did not. In summary, analysis of strains harbouring inhA or kasA plasmids yielded the same conclusion: overexpressed inhA, but not kasA, confers INH and ETH resistance to M. smegmatis, M. bovis BCG and M. tuberculosis. Therefore, InhA is the primary target of action of INH and ETH in all three species. [ABSTRACT FROM AUTHOR]

Describes a naturally occuring conjugation system present in Mycobacterium smegmatis. Mechanisms of gene transfer in the system; Evidence of conjugal transfer in the system; Differences between conjugation, transformation and transduction; Extent of DNA transfer.

The amdR (intA) regulatory gene of Aspergillus nidulans encodes a 765-amino-acid polypeptide which determines the omega-amino acid induction of at least five structural genes. The AmdR polypeptide contains a potential Zn(ll)2Cys6 DNA-binding motif which has been shown to be present in the N-terminal region of a large number of fungal activator proteins. In vitro mutagenesis of the fourth cysteine of this motif abolishes AmdR function as shown by loss of complementation of an amdR- mutation and by the AmdR- phenotype of a mutant gene replacement strain. Studies using constructs in which the proposed AmdR DNA-binding motif is replaced with that from another activator, FacB, shows that induction is independent of DNA-binding specificity and that sequences in the C-terminal region of AmdR are activation domains. Sequencing of several amdR mutant alleles which affect activation and/or induction, together with studies of deletion constructs indicate that changes in the conformation of the protein determines its activity and that this is modulated by inducers. [ABSTRACT FROM AUTHOR]

Showing that ethanol added in vitro increased the fluidity of mouse erythrocyte and synaptosomal membranes and that the same membranes Isolated from mice after chronic treatment with ethanol had increased cholesterol and were resistant to ethanol in vitro, the study suggests that the animals had adapted to the chronic presence of the drug by changing their membrane lipid composition to offset the fluidizing effects of ethanol. [ABSTRACT FROM AUTHOR]

This article presents information related to epilepsy and pregnancy group in Great Britain. The Epilepsy and Pregnancy Register in Great Britain is a prospective, observational registration and follow-up study established in 1996 by J.I. Morrow in response to uncertainty regarding the relative safety in pregnancy of recently licensed antiepileptic drugs (AED). Members of the study scientific committee include the study coordinator, four epileptologists, a clinical geneticist, obstetrician general practitioner and specialist epilepsy nurses. The study has full ethical approval for a multicentre Great Britain study.