Health status of users of hormone replacement therapy by hysterectomy status in Western Australia.

STUDY OBJECTIVES: To compare the demographic, behavioural, and biological correlates of use of hormone replacement therapy (HRT) in women with an intact uterus and women who have undergone hysterectomy. DESIGN: Cross sectional analysis of data from the Busselton Health Study and the 1994 Healthway-National Heart Foundation Risk Factor Survey. SETTING: Busselton and Perth, Western Australia, 1994. PARTICIPANTS: 2540 women aged 35-79 years. MAIN OUTCOME MEASURES: Demographic, behavioural, and biological correlates of use of HRT by hysterectomy status. RESULTS: In women with an intact uterus, after adjustment for age and place of residence, current use of HRT was significantly associated with having a professional level of occupation, ever use of alcohol, having a history of smoking, and a lower body mass index. Current users of HRT had significantly lower levels of total cholesterol and higher levels of triglycerides than non-users. In women who had undergone hysterectomy, the only non-biological characteristic associated with use of HRT was having a history of smoking. Current users of HRT had lower levels of systolic blood pressure, lower levels of LDL cholesterol, higher levels of HDL cholesterol, and higher levels of triglycerides. The association between use of HRT and participation in exercise, level of systolic blood pressure, level of HDL cholesterol, and total/HDL cholesterol ratio varied significantly by hysterectomy status. After adjustment for age and place of residence, the mean levels of systolic and diastolic blood pressure, body mass index, waist/hip ratio, LDL cholesterol, and total/HDL cholesterol ratio were highest in women who had undergone hysterectomy and were not using HRT. CONCLUSIONS: Demographic/behavioural and biological correlates of use of HRT varied depending on hysterectomy status. Demographic and behavioural characteristics were more important as selection factors for use of HRT in women with an intact uterus than in women who had undergone hysterectomy. Women who had undergone hysterectomy and were not using HRT had a significantly worse profile for CHD than did women with an intact uterus. These results indicate that any bias in estimates of the protective effect of HRT on risk of CHD in observational studies is likely to depend on the prevalence of hysterectomy within the study population. Hysterectomy status needs to be taken into account in any studies that investigate the effect of HRT on risk of CHD.

Flipping a genetic switch by subunit exchange.

The bacteriophage T4 AsiA protein is a multifunctional protein that simultaneously acts as both a repressor and activator of gene expression during the phage life cycle. These dual roles with opposing transcriptional consequences are achieved by modification of the host RNA polymerase in which AsiA binds to conserved region 4 (SR4) of sigma(70), altering the pathway of promoter selection by the holoenzyme. The mechanism by which AsiA flips this genetic switch has now been revealed, in part, from the three-dimensional structure of AsiA and the elucidation of its interaction with SR4. The structure of AsiA is that of a novel homodimer in which each monomer is constructed as a seven-helix bundle arranged in four overlapping helix-loop-helix elements. Identification of the protein interfaces for both the AsiA homodimer and the AsiA-sigma(70) complex reveals that these interfaces are coincident. Thus, the AsiA interaction with sigma(70) necessitates that the AsiA homodimer dissociate to form an AsiA-SR4 heterodimer, exchanging one protein subunit for another to alter promoter choice by RNA polymerase.

Uniform 13C/15N-labeling of DNA by tandem repeat amplification.

An optimized procedure has been described for the large-scale production of stable isotopeenriched duplex oligonucleotides of designed sequence. Large-scale production of labeled nucleotide triphosphates can be produced in this procedure simultaneously with labeled proteins, thereby providing synthetic dNMP precursors at no additional cost. The procedure is robust, with a minimum product:template yield of 800:1 overall, and produces > 99% single-length product. Tandem repeat PCR amplification is a general approach to large scale synthesis of duplex oligonucleotides and may have applications to both NMR and X-ray methods, particularly for product lengths in excess of 25 base pairs where failed sequences from solid-phase synthesis can be difficult to remove chromatographically. A drawback of the present approach is that the product is a duplex of two equal-length strands, making single-stranded products more difficult to prepare. For this reason, it could be preferable to produce single-stranded products by the [figure: see text] method of Zimmer and Crothers. Although a single base type can be selectively enriched in this approach, chemical synthesis will provide greater flexibility for labeled DNAs requiring site-specific labels at only one or a small number of nucleotide positions in the sequence. Therefore, maximum flexibility in labeling patterns can be realized by judicious choice of labeling method appropriate to the type of DNA product and extent of isotopic enrichment desired.

Development and validation of the Curtin Back Screening Questionnaire (CBSQ): a discriminative disability measure.

Disability accompanying occupational low back pain (LBP) can include a wide range of incapacitating symptoms which, for the practitioner, can be time-consuming and difficult to identify systematically. A questionnaire designed for case-finding and assessment could assist in both the early recognition of disability and in planning management. A suitable questionnaire for clinical use could not be found in the literature. The Curtin Back Screening Questionnaire (CBSQ) was developed, therefore, as a discriminative screening instrument to serve this purpose. The methods and results of the development and validation of the CBSQ are presented herein. Development of the questionnaire followed the principles of Kirschner and Guyatt (1985) employing data from 74 subjects with at least moderately severe work-related LBP. The research design for the validation was multiple-group repeated-measures with a study population of 150 subjects. The screening function of the questionnaire was developed through selecting 8 questions from the whole questionnaire using regression analysis. The questionnaire includes 79 items based on the subjects' perceived health status. The response structure of the CBSQ has been adapted from that of the General Health Questionnaire (GHQ) and some items in the CBSQ have been developed from items in the Sickness Impact Profile (SIP) and GHQ. The questionnaire discriminates effectively between subjects with different degrees of disability, it correlates quite well with the SIP, test-retest reliability for the whole questionnaire is 0.98, the receiver-operating characteristics are more favourable than those for the SIP, and the CBSQ screening score provides an index of severity which correlates with work incapacity.(ABSTRACT TRUNCATED AT 250 WORDS)