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Biomedical subjects

I White

Publications and source records attributed to I White.

At least 19 recordsLinked to original sources

Differential loss of heterozygosity in familial, sporadic, and uremic hyperparathyroidism.

Various genetic loci harboring oncogenes, tumor suppressor genes, and genes for calcium receptors have been implicated in the development of parathyroid tumors. We have carried out loss of heterozygosity (LOH) studies in chromosomes 1p, 1q, 3q, 6q, 11q, 13q, 15q, and X in a total of 89 benign parathyroid tumors. Of these, 28 were sporadic parathyroid adenomas from patients with no family history of the disease, 41 were secondary parathyroid tumors, 5 were from patients with a history of previous irradiation to the neck, 12 were from patients with a family history of hyperparathyroidism, and 3 were parathyroid tumors related to multiple endocrine neoplasia type 1 (MEN1). In addition, we determined the chromosomal localization of a second putative calcium-sensing receptor, CaS, for inclusion in the LOH studies. Based on analysis of somatic cell hybrids and fluorescent in situ hybridization to metaphase chromsomes, the gene for CaS was mapped to chromosomal region 2q21-q22. The following results were obtained from the LOH studies: (1) out of the 24 tumors that showed LOH, only 4 had more than one chromosomal region involved, (2) in the tumors from uremic patients, LOH of chromosome 3q was detected in a subset of the tumors, (3) LOH of the MEN1 region at 11q13 was the most common abnormality found in both MEN1-related and sporadic parathyroid tumours but was not a feature of the other forms of parathyroid tumors, (4) LOH in 1p and 6q was not as frequent as previously reported, and (5) tumor suppressor genes in 1q and X might have played a role, particularly on the X chromosome, in the case of familial parathyroid adenomas. We therefore conclude that the tumorigenesis of familial, sporadic, and uremic hyperparathyroidism involves different genetic triggers in a non-progressive pattern.

Adenoma

Maternal serum screening for Down's syndrome: a survey of midwives' views.

The lack of consensus regarding the implementation of maternal serum screening, has led to a widespread variation in practice. The importance of the role of midwives within the service has been recognised. All maternity units in the Northern region now have a designated 'co-ordinator' in an attempt to improve service delivery, professional liaison and training. This study was designed to obtain midwives' views about maternal serum screening in principle and to assess whether any changes had occurred since the introduction of co-ordinators. Semi-structured, postal questionnaires were sent to all midwives in one health authority for them to complete and return. Within this authority, one maternity unit offered universal screening whereas the other maintained a selective policy. Responses were obtained from 90 out of 133 (67.7%). There was almost unanimous support for the principle of screening 86 out of 90 (95.5%) and most midwives considered the offer of screening should be an NHS service, independent of age 78 out of 90 (86.7%). Half of the respondents 46 out of 90 (51.2%) reported that the introduction of a co-ordinator had been successful in improving staff education but requests for further training and updating were made by 69 out of 90 (76.6%) despite having had this organized training input: although those midwives who were regularly involved with screening made significantly fewer requests 27 out of 45 (60%). These findings confirmed our previous recommendation that ongoing responsibility for such provision would be required. The results of the study provided a useful contribution towards the review of screening policy undertaken by the health authority, as well as evidence upon which to base further development of the role of the co-ordinators in their support of midwives.

Attitude of Health Personnel

Can dietary interventions change diet and cardiovascular risk factors? A meta-analysis of randomized controlled trials.

OBJECTIVES: This study evaluated the effectiveness of dietary advice in primary prevention of chronic disease. METHODS: A meta-analysis was conducted of 17 randomized controlled trials of dietary behavior interventions of at least 3 months' duration. Results were analyzed as changes in reported dietary fat intakes and biomedical measures (serum cholesterol, urinary sodium, systolic and diastolic blood pressure) in the intervention group minus changes in the control group at 3 to 6 months and 9 to 18 months of follow-up. RESULTS: After 3 to 6 months, mean net changes in each of the five outcomes favored intervention. For dietary fat as a percentage of food energy, the change was -2.5% (95% confidence interval [CI] = -3.9%, -1.1%). Mean net changes over 9 to 18 months were as follows: serum cholesterol, -0.22 (95% CI = -0.39, -0.05) mmol/L; urinary sodium, -45.0 (95% CI = -57.1, -32.8) mmol/24 hours; systolic blood pressure, -1.9 (95% CI = -3.0, 0.8) mm Hg; and diastolic blood pressure, -1.2 (95% CI = -2.6, 0.2) mm Hg. CONCLUSIONS: Individual dietary interventions in primary prevention can achieve modest improvements in diet and cardiovascular disease risk status that are maintained for 9 to 18 months.

Cardiovascular Diseases

Audit of maternal serum screening: strategies to augment counselling in response to women's views.

Women's opinion on the maternal serum screening programme offered at one maternity unit in East Northumberland (1991-1992) was evaluated. The responses from 1,774/2,633 women showed a general acceptance of the test but 722/1,774 (40%) wanted more information and a third, more explanation. Recommendations, which included a 'gold standard' protocol, a video to complement revised patient information literature and a coordinator to facilitate interdisciplinary communication and training with support for midwives, were introduced. The audit cycle was completed by a repeat questionnaire survey of 2,489 women from the postnatal ward (1992-1994) with a 67.3% response. An overall improvement in levels of satisfaction with reduction in, but not eradication of, the need for more information and explanation had occurred. These findings have relevance to the current controversy surrounding the counselling implications of maternal serum screening and have led to the formation of a network of professionals to develop the programme in our region.

Down Syndrome

Chromosomal localization of six human forkhead genes, freac-1 (FKHL5), -3 (FKHL7), -4 (FKHL8), -5 (FKHL9), -6 (FKHL10), and -8 (FKHL12).

The forkhead family of transcription factors has been shown to be involved in the regulation of embryonic development in organisms from Drosophila to humans. Genes encoding forkhead proteins are also emerging as a new class of oncogenes with relevance for human cancer. We have used a combination of fluorescence in situ hybridization and somatic cell hybrids to map the chromosomal localizations of five previously cloned human forkhead genes, freac-1, -3, -4, -5, and -6. (HGMW-approved symbols FKHL5, FKHL7, FKHL8, FKHL9 and FKHL10). We also report the sequence and the chromosomal position of a novel human forkhead gene, freac-8 (FKHL12). The freac genes have been localized to the following positions: freac-1, 16q24; freac-3, 6p25; freac-4, 5q12-q13; freac-5, 9 pericen; freac-6, 5q34, and freac-8, 1p32.

Amino Acid Sequence

Localization of the human soluble epoxide hydrolase gene (EPHX2) to chromosomal region 8p21-p12.

Epoxide hydrolases have an important function in organisms in that they catalyze the transformation of potentially toxic or carcinogenic epoxides into the corresponding diols. In this study, the chromosomal localization was determined for the human gene encoding soluble epoxide hydrolase. A polymerase chain reaction fragment corresponding to the C-terminal region of the mouse protein was used to isolate a cosmid clone from a human genomic library. By fluorescence in situ hybridization to metaphase chromosomes, the soluble epoxide hydrolase gene was then localized to chromosomal region 8p21-p12.

Animals

Work characteristics and psychiatric disorder in civil servants in London.

STUDY OBJECTIVE: To describe the association between self reported and externally assessed work characteristics and psychiatric disorder. DESIGN: Analysis of questionnaire data collected from the first phase of the Whitehall II study, a cohort study of an employed population. SETTING: Twenty civil service departments in London. PARTICIPANTS: Altogether 6900 male and 3414 female civil servants aged 35-55 years. MAIN RESULTS: High levels of subjective social support at work, control at work, job variety, and skill use were associated with greater satisfaction and wellbeing and less psychiatric disorder measured by the 30 item general health questionnaire (GHQ). High levels of subjective work pace and conflicting demands were associated with less satisfaction and wellbeing and greater psychiatric disorder. The combined effects of work characteristics were similar to the effects of the work characteristics considered separately, except that for men there was a small interaction between psychological demands and control on the GHQ. There was little overall support for the two factor job strain model. In contrast, objective indices of work were generally not associated with the psychological indices. Findings in men and women were generally comparable and were not significantly influenced by employment grade. CONCLUSIONS: Negative affectivity and a tendency to report negatively about both work and the psychological indices may partly explain the difference in the findings between subjective and objective work characteristics. However, subjective work characteristics were still associated with psychiatric disorder after adjusting for negative affectivity. The potential confounding effects of employment grade did not explain the association between either subjective or objective work characteristics and the psychological indices. While modifications to the work environment may directly reduce certain adverse physical health effects, the influence of work place design and management on psychological wellbeing, satisfaction, and psychiatric disorder may be mediated through subjective perceptions of the work environment.

Adult

A murine replication protein accumulates temporarily in the heterochromatic regions of nuclei prior to initiation of DNA replication.

We have analyzed the expression of the murine P1 gene, the mammalian homologue of the yeast MCM3 protein, during the mitotic cell cycle. The MCM3 protein has previously been shown to be of importance for initiation of DNA replication in Saccharomyces cerevisiae. We found that the murine P1 protein was present in the nuclei of mammalian cells throughout interphase of the cell cycle. This is in contrast to the MCM3 protein, which is located in the nuclei of yeast cells only between the M and the S phase of the cell cycle. Detailed analysis of the intranuclear localization of the P1 protein during the cell cycle revealed that it accumulates transiently in the heterochromatic regions towards the end of G1. The accumulation of the P1 protein in the heterochromatic regions prior to activation of DNA replication suggests that the mammalian P1 protein is also of importance for initiation of DNA replication. The MCM2-3.5 proteins have been suggested to represent yeast equivalents of a hypothetical replication licensing factor initially described in Xenopus. Our data support this model and indicate that the murine P1 protein could function as replication licensing factor. The chromosomal localization of the P1 gene was determined by fluorescence in situ hybridization to region 6p12 in human metaphase chromosomes.

3T3 Cells

Trends in higher qualifications, 1971 to 1991.

This article has highlighted just some key features derived from a brief analysis of a small part of the statistics available from the tables on qualified manpower from the last three censuses. There is scope for wider analysis using the data on employment status, occupation and industry.

Adolescent

The human NOTCH1, 2, and 3 genes are located at chromosome positions 9q34, 1p13-p11, and 19p13.2-p13.1 in regions of neoplasia-associated translocation.

In Drosophila the Notch gene controls differentiation to various cell fates in many tissues. Three mammalian Notch homologs have recently been identified: Notch 1, 2, and 3. All three homologs are very highly conserved relative to the Drosophila Notch gene, which suggests that they are important for cell differentiation in mammals. This notion is supported by the previous finding of a truncated, translocated form of the human NOTCH1 gene (formerly TAN1) in three cases of leukemia. Given this genetic link between NOTCH1 and tumor formation, it is of interest to establish the chromosomal positions of the other two homologs. We report the identification of cosmid clones for the human NOTCH1, 2, and 3 genes. These clones were used as probes in fluorescence in situ hybridization to human metaphase chromosomes, and the results, combined with data from somatic cell hybrid panels, show that the NOTCH2 and 3 genes are located at positions 1p13-p11 and 19p13.2-p13.1, respectively, which are regions of neoplasia-associated translocation.

Amino Acid Sequence

Plagiarism or protecting public health?

Is milk produced using recombinant bovine growth hormone hazardous to animal health? Despite wide publicity, the controversy remains unresolved. Rapid publication of all available data is essential if progress is to be made.

Animals

1991 Census of Great Britain: summary of results.

All the scheduled Topic Statistics Population Statistics reports from the 1991 Census are now published. This article illustrates the Census range of statistics contained in these reports, making some comparisons with results from the 1981 Census for those topics where there are comparable figures.

Adolescent

Predisposition for breast cancer in carriers of constitutional translocation 11q;22q.

A translocation between the long arms of chromosomes 11 and 22, t(11;22)(q23;q11), is the most frequent constitutional reciprocal translocation in man. This chromosome abnormality has not previously been reported to be associated with an increased risk for neoplasia. The observation of one patient with a constitutional translocation t(11q;22q) and breast cancer prompted us to study the relationship between these two conditions. The incidence of breast cancer was determined in carriers of t(11q;22q). The karyotypes were determined by QFQ-banding, and the breakpoints were then further characterized by fluorescent in situ hybridization. Eight families with a total of 22 balanced carriers were found. In five of these families there was one case of breast cancer each. In another family a case of an unknown malignancy was reported in one member. No other malignancies were found among these patients. The number of breast cancer cases was significantly higher than expected among the translocation carriers (P < .001). The chromosomal breakpoints showed the same localization with the markers used, in the seven families studied. The association of constitutional translocation t(11q;22q) and breast cancer identifies a subset of patients with a highly increased risk for breast cancer who would benefit from counseling and screening. It also suggests the involvement of genes on 11q and/or 22q, in the tumorigenesis of breast cancer.

Breast Neoplasms

Gender differences in occupational mobility and structure of employment in the British Civil Service.

In all industrialized societies health status in adults has been found to vary with social position. Attempts to explain this are usually grouped under headings of artefact, material, lifestyle and selective mobility of the healthiest. Such attempts have to date been unsuccessful in fully accounting for this relationship, and whilst they have merit have left unconsidered the effects of the process whereby social stratification occurs. The present study is a prelude to subsequent studies that will endeavour to distinguish between three separate influences on health--the effects of current social position, the long term effects stemming from one's initial class position, and the effects of the processes governing mobility. The purpose of our present investigation is to describe patterns of occupational mobility, that will enable us to identify possible predictors of subsequent mobility and therefore to indicate to what extent mobility might be a process governed by social rules. The work presented in this paper comprises part of the Whitehall II study of occupational, social and lifestyle influences upon health in a Civil Service population. Using multiple regression techniques almost half the variation in mobility is modelled in terms of educational level, fathers' social class, gender, marital status, age on entry into the Civil Service, length of time in Civil Service employment and grade of entry into the Civil Service. Using estimates derived from this model it is suggested that a number of sub-groups within the Civil Service suffer adverse mobility (mobility appears particularly restricted for women and for those entering the Civil Service above 30 years of age). The results obtained suggest that the issue of obstructed opportunity at the workplace could become a focus for fruitful investigation, linking issues of personal autonomy, expectations and control to health. A number of methodological problems in this kind of work are considered together with discussion of how the model can be used to increase our understanding of mobility.

Adult