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Biomedical subjects

P C Whitehead

Publications and source records attributed to P C Whitehead.

At least 19 recordsLinked to original sources
PubMed1998

Structure of an XRCC1 BRCT domain: a new protein-protein interaction module.

The BRCT domain (BRCA1 C-terminus), first identified in the breast cancer suppressor protein BRCA1, is an evolutionarily conserved protein-protein interaction region of approximately 95 amino acids found in a large number of proteins involved in DNA repair, recombination and cell cycle control. Here we describe the first three-dimensional structure and fold of a BRCT domain determined by X-ray crystallography at 3.2 A resolution. The structure has been obtained from the C-terminal region of the human DNA repair protein XRCC1, and comprises a four-stranded parallel beta-sheet surrounded by three alpha-helices, which form an autonomously folded domain. The compact XRCC1 structure explains the observed sequence homology between different BRCT motifs and provides a framework for modelling other BRCT domains. Furthermore, the established structure of an XRCC1 BRCT homodimer suggests potential protein-protein interaction sites for the complementary BRCT domain in DNA ligase III, since these two domains form a stable heterodimeric complex. Based on the XRCC1 BRCT structure, we have constructed a model for the C-terminal BRCT domain of BRCA1, which frequently is mutated in familial breast and ovarian cancer. The model allows insights into the effects of such mutations on the fold of the BRCT domain.

Amino Acid Sequence↗
PubMed1994

Biochemical characterisation of purified human wild-type p53 overexpressed in insect cells.

Conditions for the overexpression of human wild-type p53 using a baculovirus construct were optimised in insect cells which produced up to 20 mg p53/1 culture. Milligram amounts of p53 were purified to apparent homogeneity using chromatography on double-stranded DNA-cellulose (approximately 58% yield) followed by immunoaffinity chromatography with an epitope elution step (up to 48% yields) at 4 degrees C. The M(r) of extracted p53 both from insect cell lysates and after purification was 54,000 by SDS/PAGE. Isoelectric focusing showed recombinant p53 to be an acidic protein, focusing at pI 6.0 under non-denaturing conditions. Expressed p53 at all stages of purification reacted by immunoblotting with specific p53 monoclonal antibodies, indicating the presence of intact epitopes at the C-terminus, N-terminus and central region of the protein. From ultracentrifugation studies, pure p53 exhibited significant oligomerisation, and sedimented broadly within the 7-12-S region of sucrose gradients. Pure p53 slowly precipitated out of solution at concentrations between 1-6 mg/ml even in the presence of 1% detergent. Using metal affinity chromatography, we have established that pure p53 binds the immobilised divalent ions Zn2+, Ni2+ and Co2+ with high affinity.

Animals↗
PubMed1993

Validity and reliability of self-reported drinking behavior: dealing with the problem of response bias.

This work assesses the validity and reliability of self-reported survey data on drinking behavior. There is evidence to suggest that data are adversely affected by bias from underreporting. This bias affects the validity of measures of consumption of alcohol and can have deleterious effects on the results of some forms of statistical estimation. Data for this study were collected at an isolated military base. The remoteness of this site and the fact that it is a military station made it possible to estimate the actual level of consumption of alcohol for the population by assessing apparent consumption through officially recorded sales of alcohol. The results of eight measures of consumption of alcohol were compared with apparent consumption, as established by documented sales, and the validity and reliability of the various measures were determined using the classical correlational approach. The validity and reliability of the data generated by the self-report survey were also analyzed using LISREL, the measurement model in particular. The results indicate that various instruments used to assess the consumption of alcohol produce very different outcomes in terms of their validity and reliability, some questions being considerably more valid and reliable than others. Two of the more salient characteristics of questions that affect validity and reliability were isolated, namely a question's ability to aid recall and its ability to mitigate the effects of persons providing socially desirable responses. The LISREL results show that these are two underlying factors for the measurement of the consumption of alcohol. It is concluded that questions that produce valid and reliable responses do so for identifiable reasons, and measurement instruments can be improved by incorporating particular features.

Alcohol Drinking↗
PubMed1991

Advertising and alcohol sales: a legal impact study.

According to the single distribution theory increases in the availability of alcoholic beverages in the general population are associated with increases in average consumption and increases in alcohol-related damage. If it can be demonstrated that advertising contributes to availability, perhaps in the form of what has been called social or subjective availability, then advertising could be considered an appropriate target of prevention. A 58-year ban on advertising of alcoholic beverages was lifted in Saskatchewan in 1983. Data on monthly sales of beer, wine and distilled spirits were examined for the years 1981 to 1987. Box-Jenkins time series techniques were used to estimate the statistical relationship between the policy change and volume of sales of alcoholic beverages. The results revealed that sales of beer increased and sales of spirits decreased following the change in legislation that permitted alcohol advertising in Saskatchewan. The main finding is that there was no impact on wine and total alcohol sales from the introduction of alcohol advertising. Alcohol advertising may have produced a substitution effect with respect to beer and spirits, but this was not predicted. This evaluation suggests that alcohol advertising is not a contributory force that influences the overall level of alcohol consumption. The place of advertising in the single distribution theory remains not proven, and the place of advertising as an instrument of public policy with respect to the prevention of alcohol-related damage remains in question.

Advertising↗
PubMed1990

Expression of beta human chorionic gonadotrophin by non-trophoblastic non-endocrine 'normal' and malignant epithelial cells.

Expression of hCG and its free subunits by non-trophoblastic tumours is well recognised. Previously we reported hCG secretion by normal and malignant bladder epithelial cells in vitro. Here we examined culture medium from 83 different cell lines derived mainly from common epithelial tumours. Thirty-two of the cell lines were found to secrete hCG-like material into their culture media. Partial immunochemical characterisation showed that of these only choriocarcinoma and fetal tissue cell lines produced intact hCG and alpha subunit. The remaining 28 hCG-expressing epithelial cell lines, which are of mucosal origin, only secreted free beta subunit. Expression of free beta hCG by non-trophoblastic nonendocrine cells would appear to be especially characteristic of mucosal epithelia from the genitourinary and oral/respiratory tracts. Furthermore, this phenomenon may be characteristic of epithelium with transitional and/or squamous cell-like properties.

Carcinoma↗
PubMed1990

Epidermolysis bullosa acquisita antigen and the carboxy terminus of type VII collagen have a common immunolocalization to anchoring fibrils and lamina densa of basement membrane.

In this study a variety of immunoelectron microscopic methods were used to define the precise ultrastructural binding site of epidermolysis bullosa acquisita antibodies (EBA-Ab). We used two EBA sera which immunoblotted with the same skin-extracted protein as that labelled by a monoclonal antibody (LH7.2) which is known to react with the carboxy terminus of type VII collagen. Gold-conjugated antibodies were used in two different immunoelectron microscopic procedures to compare the labelling characteristics of EBA-Ab and LH7.2 in normal human skin. Antibody incubations were performed using ultra-thin cryosections of unfixed skin and thin slices of fresh skin (en bloc technique) before conventional fixation and embedding in Epon. Both methods showed similar labelling features for both EBA-Ab and LH7.2. With ultra-thin cryosections there was labelling of the lamina densa and an undefined component of the sublamina densa region. With the en bloc technique, labelling of dermal ends of anchoring fibrils and of amorphous material recently defined as 'anchoring plaques' was evident. There was no labelling of the central banded portions of anchoring fibrils. We conclude that EBA-Ag is localized to the dermal ends of anchoring fibrils in addition to the lamina densa and possibly anchoring plaques, and thus has the same distribution as the carboxy terminus of type VII collagen.

Antibodies, Monoclonal↗
PubMed1989

Identification of the epidermolysis bullosa acquisita antigen by LH 7.2 monoclonal antibody: use in diagnosis.

The sera from two patients with epidermolysis bullosa acquisita were blotted against dermal extracts in comparison with the mouse monoclonal antibody LH 7.2. This antibody reacts with carboxy terminal region of type VII collagen. The epidermolysis bullosa acquisita antisera showed binding to the same molecular weight protein as LH 7.2 confirming that the target antigen for epidermolysis bullosa acquisita antibodies is the carboxy terminal region of type VII collagen. This newly described collagen forms the major component of anchoring fibrils. These findings are consistent with established ultrastructural data which have shown that the epidermolysis bullosa acquisita antigen is located within and below the lamina densa. The monoclonal antibody LH 7.2 provides an internal standard for epidermolysis bullosa acquisita autoantisera activity. The use of immunoblotting of epidermolysis bullosa autoantisera in comparison with the monoclonal antibody LH 7.2 provides definitive investigation for the diagnosis of this disorder.

Adult↗
PubMed1987

Strains toward convergence in the consumption of alcoholic beverages: the Canadian case and implications for public health.

Sulkunen's observations that international trends in the consumption of alcoholic beverages involve quantitative as well as qualitative homogenization of drinking practices are tested against the experience of Canada and its provinces from the mid 1960s to late 1970s. Per capita consumption of spirits, beer, and wine, and the contribution of each of these types of alcoholic beverages to total consumption are examined for each province for the fiscal years 1966, 1972, and 1978. On the whole, the findings are consistent with worldwide trends. Per capita consumption is increasing generally and there is a trend toward greater similarity in per capita consumption across the provinces (quantitative homogenization). Consumption of different types of beverages is becoming more similar (qualitative homogenization) and increases in the beverage with the lowest share of the market (i.e., wine) appear to be additive to overall consumption. The observation that increases in consumption of the traditional types of beverages have the most impact on overall consumption is not observed for beer, but is observed in the case of spirits. Implications for public health and social policy are discussed.

Alcohol Drinking↗
PubMed1986

Drinking and the prevention of coronary heart disease: findings, issues and public health policy.

Claims that the moderate consumption of alcoholic beverages prevents coronary heart disease are reviewed in an analysis of recent literature. Reports of such claims in the mass media are found to be exaggerated and based on research that is less conclusive than is often suggested. The review of original research reveals evidence that certain levels of consumption bestow some benefits under some circumstances when compared with other levels of consumption, including abstinence. A number of methodological issues are raised, and suggestions are made for testing competing hypotheses that may explain the association between moderate drinking and lower rates of coronary heart disease. The investigators discuss the implications of these findings for public health policy and conclude that, on the strength of the available evidence, it would be unwise to alter either the scientific or public focus on the damage caused by alcohol or to support changes in policy that might make drinking more socially acceptable and thereby encourage higher levels of consumption.

Alcohol Drinking↗
PubMed1985

Employment, marital status and alcohol consumption of young Canadian men.

This article focuses on heavy alcohol consumption among young Canadian men drinkers aged 15-29 and examines how employment status and marital status interact with age. The study found that the highest percentages of heavy drinkers occurred in men over the age of 18 who are single (divorced, separated or never married) and in the labor force, whether employed or unemployed. This study, based on cohort data, generated hypotheses that need to be tested with longitudinal data in order to better understand developmental differences and other factors that affect drinking practices.

Adolescent↗
PubMed1985

Research and treatment: the need for a combined effort.

Institutional, ideological, practical, and logistical constraints have impeded treatment research efforts in the substance abuse fields. There is a need for innovation in the design and conduct of treatment research studies, including studies that are less restrictive of therapists' judgments and more sensitive to individual client differences. Among the advantages of a greater collaboration between clinicians and researchers are the facilitation of research on the matching of clients to treatments and the enhanced impact of research findings on clinical practice.

Humans↗
PubMed1983

Values of adolescent drug abusers.

Values of adolescent drug abusers are measured with the Rokeach Value Survey and compared with the values of the parents and peers of drug abusers. Relatively few significant differences are found between groups, and there is a marked level of concordance between pairs of groups: .86 to .96. There is, however, a relatively low level of agreement within groups (.16 to .36), and the suggestion is made that focusing on the differences between value systems of users and their significant others may be of limited programmatic utility.

Adult↗
PubMed1982

The ecology of self-injury: a multivariate approach.

In an ecological study of the distribution of self-injury in London, Canada, the authors found that self-injury occurred more frequently in the central areas of the city. Multivariate analysis revealed that living arrangements, such as high density of housing and single-person households, are closely associated with inflated rates on self-injury. Low socio-economic status is also related to self-injury but neither family status nor mobility are significant predictors. Ecological relationships such as these suggest directions for future research on individuals and may also be of direct use to planners who wish to locate treatment services advantageously.

Humans↗
PubMed1978

Acupuncture in the treatment of addiction: a review and analysis.

Many claims have been made about the usefulness of acupuncture as an analgesic and in the cure of certain conditions. The background of some of these claims is examined as are alternative hypotheses for some of the observations that have been reported. The studies that have served as the basis of much of what has been said and written about the use of acupuncture in the management of addictions are reviewed and found to fall seriously short of adequate clinical trials. The utility of acupuncture remains unproven, and some directions for future research are suggested.

Acupuncture Therapy↗