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Biomedical subjects

S M Hunt

Publications and source records attributed to S M Hunt.

At least 19 recordsLinked to original sources
PubMed1999

Coexpression of alternatively spliced estrogen and progesterone receptor transcripts in human breast cancer.

Primary transcripts of the human estrogen receptor (ER) and progesterone receptor (PR) are subject to a number of alternative splicing events resulting in a range of variant messenger ribonucleic acid species in receptor-positive tissues. Despite in vitro demonstrations of a possible role for some of these variants in hormonal sensitivity, the clinical significance of this process is uncertain. In this study the coexpression of variant ER and PR transcripts has been documented by RT-PCR and Southern blot analysis in a series of receptor-positive breast tumors. In 35 ER-positive tumors, a common profile of variant ER transcripts was present, with all tumors containing the delta2ER and delta7ER, 94% containing the delta4ER, and 83% containing the delta5ER. In 25 of these cases, which were also PR positive, the most highly expressed PR variants, the delta4PR, delta6PR, and delta(4/2)PR, a transcript from which a 126-bp portion of PR exon 4 was deleted, were detected in over 90% of the cases. The alternatively spliced ER variants were expressed at higher relative levels than the PR species, which had mean levels of expression less than 10% that of wild-type PR. The most abundant species was the delta7ER, which was present at levels ranging from 29-83% of the wild type. There was no relationship between the level of delta7ER in individual tumors and the pattern of expression of the estrogen-responsive proteins PR and pS2. The common profile of alternatively spliced ER and PR transcripts in breast tumors means that this feature cannot be used as a discriminator of hormone responsiveness or other clinical end points. Further, the low level of expression of the majority of variant species calls into question their potential for impacting significantly on receptor function.

Adult↗
PubMed1998

Characterization of a truncated progesterone receptor protein in breast tumors.

The progesterone receptor (PR) mediates the actions of progesterone in the normal and malignant breast. PR is expressed as two proteins, PR B and PR A, which are expressed in normal progesterone target tissues and in breast cancers. A significant proportion of breast cancers contain, in addition, a smaller PR protein of molecular mass 78 kDa (PR78 kDa). The significance of PR78 kDa expression is unknown, and in particular, there are no data on whether PR78 kDa is able to bind ligand and therefore potentially exhibit transcriptional activity. If this smaller PR species exhibits similar differences in function as have been evidenced in vitro for PR A relative to PR B, it is possible that this PR species may be an important component in determination of progesterone response in breast cancer. The purpose of this study was to determine whether the PR78 kDa protein in breast tumors is able to bind ligand and to determine whether posttranscriptional mechanisms contribute to its formation in breast cancers. There was no evidence that PR78 kDa was derived from proteolytic activity of either PR B or PR A. Similarly, although exon-deleted PR transcripts were detected (which could, if translated, give rise to a PR protein similar in size to PR78 kDa), neither the abundance of such transcripts nor their relationship to levels of expressed PR78 kDa protein supported a role for exon deletion in formation of this truncated PR protein. PR78 kDa was not recognized by an antibody specific for PR B, indicating that, like PR A, it lacks the N-terminal portion of PR. PR78 kDa was able to bind the progestin ligand, indicating that it may have transcriptional activity. In summary, this study has shown that a truncated PR protein, found in breast cancers, is ligand-binding and seems to be derived from PR A, indicating that it may have a role in progesterone signaling, although a deeper understanding of its role, if any, in breast cancer remains to be established.

Breast Neoplasms↗
PubMed1997

Quality of life claims in trials of anti-hypertensive therapy.

The increasing use of so-called quality of life assessments in clinical trials can be seen as a laudable attempt to gather information about the impact of treatment on patients which goes beyond the purely clinical. However, there is a growing tendency for pharmaceutical companies to use quality of life claims in marketing strategies. The varying protocols and study populations, together with multicentre and multicountry trials and the variety of implied definitions of quality of life raise serious issues concerning the scientific credibility of conclusions about quality of life as an endpoint. This paper reviews reports of randomized controlled trials of anti-hypertensive therapy which used 'quality of life', assessed by patient-completed questionnaires, as one of the outcome variables. Criteria referring to definitions of quality of life, the validity and reliability of the measures used, administration procedures, treatment of data, adequacy of discussion of alternative explanations of the findings and the legitimacy of the findings are spelled out. It is concluded that none of the studies reviewed were justified in the claims made concerning differential effects of therapies on 'quality of life'.

Antihypertensive Agents↗
PubMed1996

Processing of mutated human proinsulin to mature insulin in the non-endocrine cell line, CHO.

Heterologous genes encoding proproteins, including proinsulin, generally produce mature protein when expressed in endocrine cells while unprocessed or partially processed protein is produced in non-endocrine cells. Proproteins, which are normally processed in the regulated pathway restricted to endocrine cells, do not always contain the recognition sequence for cleavage by furin, the endoprotease specific to the constitutive pathway, the principal protein processing pathway in non-endocrine cells. Human proinsulin consists of B-Chain-C-peptide-A-Chain and cleavage at the B/C and C/A junctions is required for processing. The B/C, but not the C/A junction, is recognised and cleaved in the constitute pathway. We expressed a human proinsulin and a mutated proinsulin gene with an engineered furin recognition sequence at the C/A junction and compared the processing efficiency of the mutant and native proinsulin in Chinese Hamster Ovary cells. The processing efficiency of the mutant proinsulin was 56% relative to 0.7% for native proinsulin. However, despite similar levels of mRNA being expressed in both cell lines, the absolute levels of immunoreactive insulin, normalized against mRNA levels, were 18-fold lower in the mutant proinsulin-expressing cells. As a result, there was only a marginal increase in absolute levels of insulin produced by these cells. This unexpected finding may result from preferential degradation of insulin in non-endocrine cells which lack the protection offered by the secretory granules found in endocrine cells.

Animals↗
PubMed1996

Housing conditions and mental health in a disadvantaged area in Scotland.

OBJECTIVE: To examine the mental health impact of different aspects of poor housing. DESIGN: This was a post hoc analysis of data from a household interview survey. SETTING: A public sector housing estate on the outskirts of Glasgow. SUBJECTS: These comprised 114 men and 333 women aged between 17 and 65 from 451 households. MEASURES: Dependent variable: scoring > or = 5 on the 30 item general health questionnaire (GHQ30). INDEPENDENT VARIABLES: self reported data on household composition, whether ill health was a factor in the move to the current dwelling, length of time at address, household income, whether the respondent was employed, chronic illness, and 6 problems with the dwelling. RESULTS: Reporting a problem with dampness was significantly and independently associated with scores of > or = 5 on the GHQ30 after controlling for possible confounding variables. CONCLUSION: Initiatives to tackle housing dampness may be important in developing a strategy to improve mental health for the study area. More research on the mental health impact of different aspects of poor housing is required.

Adolescent↗
PubMed1995

Measuring psychological well-being. The adapted General Well-Being Index in a primary care setting: a test of validity.

The measurement of health outcomes is central to the development of health services. Many acute and chronic illnesses and health interventions have implications for mental health. This study tests the validity of a 22 item measure of psychological well-being, the adapted general well-being index (AGWBI). A postal health survey, including the AGWBI, was sent to a 10% random sample of patients aged 16 or over drawn from the computerized list of one general practice. Two hundred and sixty-six respondents returned questionnaires (a response rate of 76%). The AGWBI was fully completed by 94% (249) of the respondents who returned their questionnaires. Only respondents who fully completed the AGWBI are included in the analysis. The AGWBI significantly discriminated people with a limiting long term illness, those reporting suffering from anxiety, depression or bad nerves, users of general practitioner services over the previous two weeks and respondents reporting taking anti-depressants, tranquillizers or sleeping tablets. It was also able to discriminate respondents with psychosocial difficulties in a small sub-sample who reported that they were in excellent health and did not have a limiting long term health problem or psychological illness. The results are broadly supportive of the validity of the AGWBI and suggest it may be appropriate for use in the evaluation of several developing areas of primary care. Further research is needed to test concurrent validity, responsiveness and to establish population norms.

Adolescent↗
PubMed1994

A measure of family disruption for use in chickenpox and other childhood illnesses.

A search of the literature showed the lack of a suitable measure for assessing the impact of minor illness on children and their families. Such illness can lead to considerable disruption within the family and particularly to the parent primarily responsible for the care of the ill child. Discussion groups were run with parents who had a child who had had chickenpox within the previous 6 months. Analysis of the transcripts from the groups produced items indicating three types of disruption; parents' distress, changes in the behaviour of the ill child and general disruption to family arrangements. Items from the transcripts were formed into a questionnaire which was then used in a study of 61 families in which a child had become ill with chickenpox within the previous 7 days. The principal carer completed the measure every evening for a fortnight. The results of the study showed considerable disruption over the first few days of the child's illness, followed by a steady reduction over the whole 2-week period.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1993

Childhood chickenpox: its impact on child and family.

Sixty-nine parents took part in nine discussion groups designed to explore the effect of childhood chickenpox on the behaviour of the affected child, on family routines and on the parents themselves. Although most parents thought of chickenpox as a relatively trivial illness, it was found that there was considerable disruption to family organization and plans and, often, great strain was imposed on a parent, usually the mother. Some families incurred extra financial burdens in terms of time taken from work, the purchase of over the counter preparations, childminders and special treats for the sick child. It was apparent that parents needed more information and reassurance about the nature and course of the illness.

Adolescent↗
PubMed1993

Preliminary report on the development of a disease-specific instrument for assessing quality of life of adults with growth hormone deficiency.

It is notable that many of the feelings described by the people in the sample are similar to those experienced at times by people who do not suffer from GHD, that is, lapses of memory, feeling drained of energy, loss of temper, loss of motivation, difficulty in concentrating, forgetfulness and having a tendency to gain weight. Adults with GHD, however, appear to suffer these problems more frequently and to a more extreme degree than other people. It is clear that the range of problems that afflict people with GHD is great, and that the repercussions affect virtually all aspects of their lives. The results from these interviews will form the basis of a measure designed specifically to assess the quality of life of patients with GHD, and to determine the changes in quality of life after treatment with GH.

Adult↗
PubMed1992

The QLDS: a scale for the measurement of quality of life in depression.

It has been apparent for some time that utilisation of health services is more influenced by how people feel than by their 'objective' symptoms. Research has also shown that compliance with treatment regimens is dependent on the impact of that treatment on the patient's well-being. Such findings highlight the need to assess the patient's view of his or her progress through the health care system. This has led to a growing interest in quality of life assessment and, in particular, to the impact of illness and its treatment on the quality of life of the patient. Perhaps surprisingly, interest in quality of life measures for outcome assessment in Psychiatry has been slower to develop than in other specialties. While a number of clinician- and patient-completed measures of the severity of depressive symptoms exist, no measure of the quality of life of depressed patients is available. This paper describes the development and testing of the Quality of Life in Depression Scale (QLDS), a new measure designed to fill this gap. The theoretical basis for the instrument is that life gains its quality from the ability and capacity of the individual to satisfy his or her needs. The items included in the QLDS were derived from 30 qualitative interviews with depressed or recently recovered patients. Further interviews were held with depressed patients to establish the face and content validity of the instrument. Respondents had little trouble completing the questionnaire and found the content to be relevant to their experience of depression. The QLDS represents an important advance in our ability to understand the impact of depression on quality of life.

Depression↗
PubMed1992

A new measure of quality of life in depression: testing the reliability and construct validity of the QLDS.

Our previous paper described the development of a new quality of life scale for use with people suffering from depression; the Quality of Life in Depression Scale (QLDS). This paper reports on the testing of the scale for reliability and construct validity. Reliability was assessed by giving the questionnaire to the same set of patients on two occasions 2 weeks apart. This test-retest technique yielded a correlation of 0.94, with high internal consistency at both time 1 and time 2. A test of split-half reliability also indicated very high reliability. Construct validity was measured by comparing scores on the QLDS with those on an established scale of well-being from the same group of patients. The results gave a correlation between the two measures of 0.79, giving a satisfactory validity. It is concluded that the QLDS is a reliable and valid measure which is easy to use and acceptable to patients. Further tests of discriminative, concurrent and criterion validity are planned.

Depression↗
PubMed1992

Induced expression of a Drosophila hsp70 promoter-fusion transgene is reduced after repeated heat shocks.

Levels of transcripts produced by a heat shock protein 70 (hsp70)-antisense white transgene in Drosophila were measured after single and multiple heat shocks to determine whether the hsp70 promoter could produce sustained high levels of transgene transcripts. A single heat shock resulted in typical highly inducible levels of RNA, but the amount of antisense RNA was substantially reduced after multiple heat shocks. Endogenous hsp70 mRNA levels were also less abundant after multiple heat shocks as compared to a single heat shock. The hsp70 promoter is unsuitable for use in fusion gene constructs for long term expression studies where repeated heat shocks are required.

Animals↗
PubMed1991

Cross-cultural adaptation of health measures. European Group for Health Management and Quality of Life Assessment.

There is increasing interest throughout Europe in measuring health needs in the general population and in the 'quality of life' of patients. This has led to a demand for questionnaires capable of measuring health status in a reliable and valid manner. Most existing measures have, however, been standardised only in the U.S.A. and, to a lesser extent, in the U.K. The issue of translation and retesting of questionnaires prepared in the English language for use in other countries has received surprisingly little attention. This paper describes some of the technical, linguistic and conceptual issues raised by translation and the processes involved in producing acceptable country-specific versions of the Nottingham Health Profile according to a systematic method.

Cross-Cultural Comparison↗