Mothers tended to rate social support as more important than health service support. Health service support was described unfavourably with emphasis on time pressures, lack of availability of healthcare professionals or guidance, promotion of unhelpful practices and conflicting advice. Changes are required within the health services to address the needs of both mothers and staff.

We have analyzed the promoter region of the human BRCA1 gene in detail and demonstrate that the expression of the BRCA1 gene is under complex regulation. First, its transcription is under the control of two promoters generating two distinct transcripts ␣ and ␤, and second, promoter ␣ is shared with the adjacent NBR2 gene and is bi-directional. Both promoter ␣ and promoter ␤ are responsive to estrogen stimulation. We also discerned that there are striking differences in both the genomic organization and immediate cis-control elements of the BRCA1 gene between humans and mice.Since its isolation in 1994 (1), much effort has been devoted toward unraveling the biological function of the breast and ovarian cancer susceptibility gene, BRCA1. The fact that many germline mutations have been found has firmly established the involvement of the BRCA1 gene in familial breast and/or ovarian cancer (2). However, unlike the precedent of other tumor suppressor genes where mutant forms of the gene products are responsible for both the inherited and sporadic forms of the same type of cancer, no sporadic breast cancers and only a handful of sporadic ovarian cancers have been found to harbor BRCA1 mutations (3-5). It is thus postulated that either BRCA1 is involved only in the etiology of inherited breast cancer or that BRCA1 disruption in sporadic cancer occurs by mechanisms other than mutations in the coding region. A few lines of evidence are consistent with the latter hypothesis: in sporadic breast cancer the BRCA1 mRNA levels are decreased (6), while in familial breast cancer inferred regulatory mutations are present (2). Therefore, studies aimed at determining the regulation of the BRCA1 gene will be critical in helping to resolve this enigma as well as to understand the normal function of the gene product.We have previously established a comprehensive map of approximately 50-kilobase pair genomic DNA encompassing not only the 5Ј end of the BRCA1 gene but also the nearby NBR1 gene (previously named 1A1-3B) (7), which was isolated as a candidate for the ovarian cancer marker CA125 (8). The 5Ј ends of both genes are duplicated with a partial copy of the BRCA1 gene lying head to head with the NBR1 gene and a partial copy of the NBR1 gene lying head to head with the BRCA1 gene ( Fig. 1) (7). Further analysis of the expression of the partial copies of both genes showed that the partial copy of the NBR1 5Ј exons is in fact part of a new gene, NBR2 (9). The fact that the transcription start sites of the BRCA1 and NBR2 genes are only 218 bp 1 apart suggests that the intergenic region may function as a bi-directional promoter. In addition, we have previously identified two distinct BRCA1 transcripts differing by the alternative use of the first exons, predicting that the BRCA1 gene is regulated by two promoters (10). This study is therefore aimed at unravelling the regulation of the BRCA1 gene by functional analysis of the BRCA1 promoters. EXPERIMENTAL PROCEDURESConstruction of Plasmids-Plasmid p3ba containing the 5Ј region of both BR...

In order to examine the onset of the cystic fibrosis (CF) disease process, the expression of the cystic fibrosis gene (CFTR) has been examined in mid-trimester human foetal tissues by in situ hybridization. CFTR mRNA was detected in the epithelia of pancreatic ducts, small intestine, colon, genital ducts, lung and trachea. The majority of these sites of CFTR expression in the foetus are similar to those seen in adult tissues. However, epithelia of the lung, that contain very little CFTR mRNA in the adult, express high levels of CFTR mRNA in the foetus. Since the lung is the major site of pathology and morbidity in CF these findings have implications for treatment.

A simple, brief intervention increased medication adherence in stroke survivors, over and above any effect of increased patient contact or mere measurement.

Using primer extension and 5' RACE, we have mapped the 5' end of the BRCA1 gene and identified a new 5' exon. Two distinct BRCA1 transcripts differing by the first exons were found; these transcripts were generated by the alternative use of dual promoters and alternative splicing. The expression of the distinct transcripts was examined in four primary tissues (placenta, mammary gland, testis and thymus), six normal or cancer cell lines, four primary breast tumor tissues and four primary ovary tumour tissues. Both transcripts were detected in all the samples studied, with the exon 1a transcript being the major expressed form in mammary gland and the exon 1b transcript in placenta. This suggests that the two transcripts may be expressed in a tissue-specific fashion. The 5' flanking regions of both BRCA1 transcripts were analysed, neither contains a TATA box. Initiator elements, which have been proposed to mediate transcription in TATA-less promoters, were found at the transcription initiation sites. Transcription factor binding sites such as Sp1, PEA3, C/EBP, CREB, E4F1 and Pu boxes were identified in the 5' flanking regions of the exon 1a transcript, and Sp1, NF-kB and PEA3 binding sites in the 5' flanking region of the exon 1b transcript. The interactions of these DNA elements with trans-acting factors are likely to modulate the alternative use of the distinct transcription start sites and the expression of the BRCA1 gene.

Our findings suggest that appropriate medication and illness beliefs coupled with a stable medication routine are helpful in achieving optimal medication adherence in stroke patients. Interventions designed to target both intentional and non-intentional adherence may help maximize medication adherence in stroke patients.

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The results suggest that successful weight maintainers, irrespective of current weight band, adopt a staged behavioural approach to weight management that allows them to maintain a fairly stable weight. Encouraging the use of such strategies in those who typically regain weight after dieting may aid them in maintaining weight loss.