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Biomedical subjects

A Wyllie

Publications and source records attributed to A Wyllie.

At least 19 recordsLinked to original sources
PubMed2000

NF-kappaB inhibits apoptosis in murine mammary epithelia.

The transcription factor NF-kappaB is a key modulator of apoptosis in a variety of cell types, but to date this specific function of NF-kappaB has not been demonstrated in epithelia. Here, we describe the activation of NF-kappaB during post-lactational involution of the mouse mammary gland, a period of extensive apoptosis of luminal epithelial cells. Significantly, active NF-kappaB localized exclusively to nonapoptotic epithelial cells both in vivo and in the mammary epithelial cell line, KIM-2, transduced with an NF-kappaB-dependent green fluorescent protein reporter. Activation of NF-kappaB in vitro coincided with a decrease in the cytosolic repressor, IkappaBalpha. Furthermore, induction of NF-kappaB either by extracellular ligands or, more specifically, by inhibition of the IkappaB repressor with adenoviral constructs expressing antisense mRNA, resulted in enhanced survival of KIM-2 cells. Therefore, although coincident with induction of apoptosis both in vivo and in vitro, NF-kappaB appeared to exert a selective survival function in epithelial cells. This study highlights for the first time a role for NF-kappaB in modulating apoptosis in epithelium.

Adenoviridae↗
PubMed2000

Risk functions for frequency of alcohol-related negative consequences: New Zealand survey data.

AIMS: To examine the dose-response relationship between self-reported alcohol consumption and levels of self-reported negative consequences of drinking. DESIGN: Data from 10 general population random sample surveys over the years 1990-1997 were combined and responses were plotted and subjected to regression analysis. SETTING: Auckland, a city of approximately 1 million people in the North Island of New Zealand. Participants were interviewed in their homes using a computer-assisted telephone interviewing system. PARTICIPANTS: General population sample of 11,817 aged 14-65 years, representative of the Auckland population. MEASUREMENTS: Frequency of experience of 14 negative consequences; annual volume of alcohol consumed; frequency of drinking larger quantities of alcohol. RESULTS: Three different patterns of relationship between consequences and consumption were found for different consequences. These differed between the prevalence and the frequency of consequences but were similar for two different measures of consumption, annual volume and larger quantity drinking. Analysis of the frequency of experienced consequences found that the risk curves for the most common consequences approximated a straight line and the effects at low volume intake were due to those drinking larger quantities. Three less common consequences clearly showed a concave curve suggesting a threshold effect, with effects beginning at about 20 litres per annum of absolute alcohol. CONCLUSION: The different relationships between consumption and consequences imply that some consequences occur only once a very heavy volume of drinking is reached, while others show a direct relationship with consumption, reflecting that volume of alcohol consumed is closely related to the quantities consumed.

Adolescent↗
PubMed1999

Somatic frameshift mutations in the MBD4 gene of sporadic colon cancers with mismatch repair deficiency.

Defects of mismatch repair are thought to be responsible for carcinogenesis in hereditary non-polyposis colorectal cancer and about 15% of sporadic colon cancers. The phenotype is seen as microsatellite instability and is known to be caused either by mutations in mismatch repair genes or by aberrant methylation of these genes stabilizing their downregulation. Lack of repair of microsatellite sequence errors, created during replication, leads to a mutation-prone phenotype. Where mutations occur within mononucleotide tracts within exons they cause translation frameshifts, premature cessation of translation and abnormal protein expression. Such mutations have been observed in the TGFbetaRII, BAX, IGFIIR, MSH3 and MSH6 genes in colon and other cancers. We describe here frameshift mutations affecting the gene for the methyl-CpG binding thymine glycosylase, MBD4, in over 40% of microsatellite unstable sporadic colon cancers. The mutations all appear heterozygous but their location would ensure truncation of the protein between the methyl-CpG binding and glycosylase domains, thus potentially generating a dominant negative effect. It is thus possible that such mutations enhance mutation frequency at other sites in these tumours. A suggestion has been made that MBD4 (MED1) mutations may lead to an increased rate of microsatellite instability but this mechanism appears unlikely due to the nature of mutations we have found.

Base Pair Mismatch↗
PubMed1999

Apoptosis: the germs of death.

From the initial recognition that programmed cell suicide existed, to the elucidation of the underlying death and survival pathways at the molecular level, the story of apoptosis has unfolded rapidly. But much still remains to be discovered.

Animals↗
PubMed1999

The extent and nature of televised food advertising to New Zealand children and adolescents.

OBJECTIVE: There has been international concern over the balance of television advertising for healthy and less-healthy foods to which children and adolescents are exposed. This study examined the extent to which 9-17 year old New Zealanders were exposed to advertising for different food groups over a year and compared New Zealand rates of advertising with a 13-country study. METHOD: 'People meter' data collected over three months--May and September 1995 and February 1996--and food advertising from a sample week of television during hours when children were likely to be watching were also examined. Comparison was made with a similar 1989 South Australian study and an international study covering 13 countries. RESULTS: Both the exposure estimated for a year and the opportunities for exposure during the sample week were highest for sweet snacks, drinks, fast food/takeaways and breakfast cereals. There were very low levels for fruit, vegetables, and meat/fish/eggs. Water was not advertised in any sample month. Comparisons with the 13-country study showed New Zealand had the third-highest rate of food advertising, the highest rate of confectionery and drinks advertising, and the second-highest rate of restaurant advertising which included fast food restaurants. CONCLUSION: Current patterns of food advertising pose a conflict of interest between public health and commercial interests. Regulation of food advertising may be needed to address this in order to improve future health.

Adolescent↗
PubMed1998

Responses to televised alcohol advertisements associated with drinking behaviour of 10-17-year-olds.

AIMS: To examine the nature of the relationships between 10-17-year-old New Zealanders' responses to alcohol advertisements and their drinking behaviour and future drinking expectations, with consideration also being given to the role of positive and negative beliefs about drinking. DESIGN: Survey involving 500 face-to-face interviews, with selection based on random cluster sampling. SETTING: In respondents' homes in New Zealand's three largest urban areas. PARTICIPANTS: Ten-17-year-old New Zealanders. MEASUREMENTS: Response to specific alcohol advertisements was measured by recalled exposure (how often they recalled having seen the advertisements) and liking (a measure of positive response). FINDINGS: An exploratory structural equation model provided tentative support for the theory-based hypothesis that positive responses to beer advertisements increased the frequency of current drinking and expected future drinking, among this age group. There was no evidence for the hypothesized reciprocal effects; the frequency of drinking (including non-drinking) did not significantly affect the respondent's liking of beer advertisements. There was also no support for a hypothesis that linking of the beer advertisements was a product of a general liking for alcohol. Many of the young people themselves felt that alcohol advertising encouraged teenagers to drink. This was especially the case among 10-13-year-old males, who were the most likely to accept the portrayals in alcohol advertising as realistic. CONCLUSIONS: Although there are limitations on the confidence with which conclusions can be drawn, the findings are consistent with qualitative and quantitative research and different theoretical perspectives on advertising processes which suggest alcohol advertising is likely to have some influence on young people.

Adolescent↗
PubMed1998

Positive responses to televised beer advertisements associated with drinking and problems reported by 18 to 29-year-olds.

AIMS: To examine the nature of the relationships between responses to alcohol advertisements and drinking behaviour and related problems. To examine the role of positive and negative beliefs about drinking as intervening variables. DESIGN: Survey utilizing a CATI (computer-assisted telephone interviewing) system, involving interviews with 1012 randomly selected respondents. SETTING: Respondents were randomly selected from throughout New Zealand. PARTICIPANTS: Eighteen to twenty-nine-year-old New Zealanders. MEASUREMENTS: Response to specific alcohol advertisements was measured by recalled exposure (how often they recalled having seen the advertisements) and liking (a measure of positive response). FINDINGS: An exploratory non-recursive structural equation model, based on 791 drinkers provided tentative support for the hypothesis that positive responses to televised beer advertisements (as measured by liking) contributed to the quantity of alcohol consumed on drinking occasions, which in turn contributed to the level of alcohol-related problems. The model, which provided a good fit to the data, was consistent with the hypothesis that liking of beer advertisements had both a direct influence on quantities of alcohol consumed and an indirect influence, via its influence on positive beliefs. These effects were present after controlling for reciprocal effects, none of which were significant. The data did not support the hypothesis that the quantities of alcohol consumed would influence the respondent's liking of beer advertisements. Recalled exposure was not a significant influence on the quantities consumed. CONCLUSIONS: The results are consistent with a number of theoretical perspectives and with a growing body of research that are suggestive of alcohol advertising having some influence on the consumption of younger people.

Adolescent↗
PubMed1997

p53 is not required for regulation of apoptosis or radioprotection by interleukin-3.

Primary interleukin-3 (IL-3)-dependent mast cell cultures from bone marrow of p53-null mice and littermate controls were established. Both p53-null and wild-type cells entered apoptosis on IL-3 removal, showing that p53 is not required for entry into apoptosis after factor deprivation. After X-irradiation, a lower proportion of the p53-null than wild-type cells underwent G2 arrest, but their radiosensitivity was similar. An IL-3-dependent cell line expressing wild-type p53 was used to show that cells die at a fixed time after X-irradiation rather than from a specific cell cycle point.

Animals↗
PubMed1997

"Becoming a mother'--developing a new theory of early motherhood.

This paper explains the methods used in a grounded theory analysis of the experience of 55 first-time mothers in Australia, presented in the first of this series of two papers. The categories identified in the research are realising, readiness, drained, aloneness, loss and working it out, encompassed in the core category becoming a mother. Specifically, this paper extends the analysis and explains the application of a 'paradigm model' and the identification of a Basic Social Process (BSP). The paper links the analysis to the literature on early motherhood from nursing, midwifery, feminist, and sociological research. A substantive theory is proposed to explain women's experience in becoming mothers that demonstrates how, when responsive to the needs of those researched, a grounded theory analysis can provide a framework for nursing and midwifery care.

Adaptation, Psychological↗
PubMed1997

Becoming a mother--an analysis of women's experience of early motherhood.

This paper presents the results of a qualitative study conducted by midwife researchers into women's experience of new motherhood. Data were collected using focus groups involving 55 first-time mothers and analysed using grounded theory method. The analysis produced six categories: 'realizing', 'unready', 'drained', 'aloneness', 'loss' and 'working it out'. The core category, 'becoming a mother', integrates all other categories and encapsulates the process of change experienced by women. Also explained are factors mediating the often distressing experience of becoming a mother. The analysis provides a conceptualization of early motherhood enabling the development of strategies for midwives, nurses and other helping women negotiate this challenge.

Adaptation, Psychological↗
PubMed1996

Analysis of mismatch repair genes in hereditary non-polyposis colorectal cancer patients.

Hereditary non-polyposis colorectal cancer (HNPCC) is an autosomal dominant disorder characterized by the early onset of colorectal cancer and linked to germline defects in at least four mismatch repair genes. Although much has been learned about the molecular pathogenesis of this disease, questions related to effective presymptomatic diagnosis are largely unanswered because of its genetic complexity. In this study, we evaluated tumors from 74 HNPCC kindreds for genomic instability characteristic of a mismatch repair deficiency and found such instability in 92% of the kindreds. The entire coding regions of the five known human mismatch repair genes were evaluated in 48 kindreds with instability, and mutations were identified in 70%. This study demonstrates that a combination of techniques can be used to genetically diagnose tumor susceptibility in the majority of HNPCC kindreds and lays the foundation for genetic testing of this relatively common disease.

Base Sequence↗
PubMed1995

Induction of apoptosis in NIH3T3 cells after serum deprivation by overexpression of rho-p21, a GTPase protein of the ras superfamily.

Oncogenes appear to influence apoptosis in two ways. Some activate cells from a growth-arrested state to one in which both apoptosis and entry to S-phase become possible, the choice between them being determined by a second signal, such as cytokine or growth factor. Cells in this state are often sensitive to apoptosis induced by a wide variety of agents, including several drugs used in cancer chemotherapy. Other oncogenes prevent activation of the apoptosis effector pathway, even in the presence of a death stimulus, the affected cells therefore being resistant to chemotherapeutic agents. In rodent fibroblasts, c-myc or the adenovirus oncogene E1A effect the first type of change, whereas bcl-2, v-abl, E1B or activated ras effect the second. Here we study in rodent fibroblast the effect of expression of rho genes, members of the ras superfamily which we have previously shown to be tumorigenic when highly expressed in this cell type. We show that expression of wild-type rho from Aplysia californica stimulates apoptosis in cultured cell lines and that the apoptotic index in tumors generated by these cell lines is similar to those induced by E1A-transformed cells. In contrast, mutated rho, activated by Val14 substitution in the GTP binding site, it less potent as a stimulator of apoptosis, generating a phenotype more similar to that obtained with activated ras. Thus, rho genes may play a critical role in the regulation of apoptosis.

3T3 Cells↗
PubMed1994

Comparison of six alcohol consumption measures from survey data.

Data were collected from a national sample of 1680 New Zealanders that allowed comparison of six different alcohol consumption measures. A measure based on reports of typical frequency and the amount typically consumed in 15 specified drinking locations produced the highest estimate of consumption. This measure and three others showed a particularly high degree of correlation, these being: a measure based on typical frequency and typical occasion amount; a variation of the Finnish period estimate; and a New Zealand variation of the period estimate that incorporated a typical frequency measure. The four measures just described, together with a last 7 days measure, showed generally consistent results when data were examined at the level of the total population and age, gender and socio-economic sub-groups. A measure based on the last two drinking occasions showed the least consistency with the other measures. The high degree of consistency found in the present study is similar to that found in a previous Finnish study and gives confidence that different ways of obtaining information about alcohol consumption, including relatively quick methods, can lead to similar conclusions about the comparative drinking of population sub-groups.

Adult↗
PubMed1993

The importance of amount and location of drinking for the experience of alcohol-related problems.

People's self report of a variety of alcohol-related problems was collected as part of a national survey carried out in New Zealand in 1988. These problems included self perception of adverse effects of drinking on a number of life areas such as health, friendships and financial position; items covering tangible consequences of alcohol use and items suggestive of alcohol dependence. The experience of these problems was predicted from a number of socio-demographic variables and respondent's reports of their typical drinking behaviour. Of the socio-demographic variables only age was found to relate strongly to experience of problems. The overall frequency of drinking relatively large amounts and the typical quantity drunk in certain licensed premises (hotels, taverns and clubs) and the typical quantity drunk in others' homes predicted the experience of problems. These findings are similar to research from other countries using different methodologies and support the likely effectiveness of prevention strategies which reduce the access of young people to alcohol and which aim to influence the amounts consumed in drinking sessions on licensed premises.

Adolescent↗