Mitochondrial DNA damage in non-melanoma skin cancer

Mitochondrial DNA (mtDNA) damage, predominantly encompassing point mutations, has been reported in a variety of cancers. Here we present in human skin, the first detailed study of the distribution of multiple forms of mtDNA damage in nonmelanoma skin cancer (NMSC) compared to histologically normal perilesional dermis and epidermis. We present the first entire spectrum of deletions found between different types of skin tumours and perilesional skin. In addition, we provide the first quantitative data for the incidence of the common deletion as well as the first report of specific tandem duplications in tumours from any tissue. Importantly, this work shows that there are clear differences in the distribution of deletions between the tumour and the histologically normal perilesional skin. Furthermore, DNA sequencing of four mutation 'hotspot' regions of the mitochondrial genome identified a previously unreported somatic heteroplasmic mutation in an SCC patient. In addition, 81 unreported and reported homoplasmic single base changes were identified in the other NMSC patients. Unlike the distribution of deletions and the heteroplasmic mutation, these homoplasmic mutations were present in both tumour and perilesional skin, which suggests that for some genetic studies the traditional use of histologically normal perilesional skin from NMSC patients may be limited. Currently, it is unclear whether mtDNA damage has a direct link to skin cancer or it may simply reflect an underlying nuclear DNA instability.     

The effects of antibodies to heat shock protein 70 in fertilization and embryo development

The role of heat shock proteins in shielding organisms from environmental stress is illustrated by the large-scale synthesis of these proteins by the organisms studied to date. However, recent evidence also suggests an important role for heat shock proteins in fertilization and early development of mammalian embryos. We found that the presence of anti-HSP70 antibody significantly reduced tight binding of spermatozoa to the zona pellucida of bovine oocytes and interrupted completion of meiosis II and pronuclear formation. Furthermore, the presence of anti-HSP70 in culture medium from day 3 to day 9 of development increased apoptosis and significantly reduced the number of embryos reaching the blastocyst stage. We further observed that the proportion of apoptotic cells in bovine blastocysts was significantly lower after in-vitro culture with a prior exposure to increased temperature. However, nuclear localization of the p53 protein, which is thought to be essential for the up-regulation of genes involved in apoptosis and cell cycle arrest, was detected in the majority of nuclei in blastocysts exposed to increased temperature, whereas in their untreated (control) counterparts, p53 protein was only detected in the cytoplasm. The decrease in apoptosis after exposure of blastocysts to increased temperature may be attributed to cell cycle arrest resulting from nuclear localization of the p53 protein and/or to an increase in heat shock protein synthesis. We propose that HSP70 plays a critical role in fertilization and early embryonic development.     

Exposure information in European industry: implications for future occupational research

A survey has been carried out among European industry to investigate the collection and retention of records which might be used for epidemiological research. Exposure information results are reported. Approximately 1,000 questionnaires focusing on exposure information were sent to seven countries, with a 42 percent response rate. Eighty-two percent of companies reported that exposure measurements were taken to comply with legal requirements. Measurements were most often made for noise (84%), with 48% of companies measuring chemicals, 48 percent particulates but only 10 percent vibration. Measurements were most often taken for specific locations (73%), rather than for particular jobs (54%) or individual workers (50%). Eighty percent recorded location, sampling date, agents measured, and units of measurement, with about 70 percent recording job being sampled, sampling method, and duration and plant process, but less than 60 percent recording environmental conditions or worker details. Overall, only 10 percent of companies kept their exposure information forever, and 71 percent kept it for 10 years or less. Legislative requirements were most often cited as the reason for retention of records. The variation in the quantity and quality of measurements and the early destruction of records poses considerable problems for European research. Inaccuracy and misclassification of exposure limits the ability to establish causal relationships between effect and disease. Records should uniquely identify an individual worker and facilitate linkage to exposure and health effects information. Their format should be accessible, linkable, and secure. Data should be kept by an identifiable organization and there should be a secure chain of custody if a company goes out of business. Unless industry can be motivated to follow these guidelines the future of research into occupational causes of ill health, and in particular, the evaluation of exposure, will be limited.     

Assessment of Ilizarov correction of club-foot deformity using pedobarography. A preliminary report

Relapsed congenital talipes equinovarus is difficult to assess and treat. Pedobarography provides dynamic measurement of the pressures under the foot, and may be used in the assessment of these patients both before and after operation. Our findings showed a statistically significant difference in the distribution of pressure across the foot after treatment by the Ilizarov technique.     

Prevalence of risk factors for cardiovascular disease in Canadians 55 to 74 years of age: results from the Canadian Heart Health Surveys, 1986-1992

BACKGROUND: By 2016, the proportion of Canadians older than 65 years of age will increase to 16%, and there will be an increase in the absolute number of cases of cardiovascular disease in older Canadians. The Canadian Heart Health Surveys database provides information about this population upon which health policy related to cardiovascular disease can be based. This paper presents for the first time population-based data on the risk factors for cardiovascular disease in older Canadians. METHODS: Canadians from all 10 provinces participated in surveys of cardiovascular risk factors; health insurance registries were used as sampling frames. In each province, probability samples of 2200 adults 18 to 74 years old not living in institutions, on reserves or in military camps were asked to participate in interviews and to undergo testing at clinics for major risk factors for cardiovascular disease. RESULTS: A total of 2739 men (response rate 70%) and 2617 women (response rate 66%) aged 55 to 74 years participated in the survey and also provided follow-up clinical measurements at the clinic. Overall, 52% of participants were hypertensive, 26% had isolated systolic hypertension, and 30% had a total blood cholesterol level of 6.2 mmol/L or greater. Rates of current smoking were lower in women than men (17% v. 22%). Overall, 87% of men and 78% of women who were current smokers smoked at least 10 cigarettes per day. Only slightly more than half of participants exercised at least once a week for at least 15 minutes, and almost half had a body mass index of 27 or greater. In only 4% was no major risk factor for cardiovascular disease detected. INTERPRETATION: Significant numbers of older Canadians have one or more major risk factors for cardiovascular disease. Many of these risk factors are amenable to modification.     

Precise intraoperative location of gastrointestinal bleeding with a hand-held counter. Work in progress

The nuclear medicine bleeding scan is frequently insufficient to locate sites of bleeding precisely, in spite of its great sensitivity. A small, hand-held Geiger-Müller counter, placed directly on exposed intestine in the operating room, enables precise location of the probable bleeding site. In three patients, the technique allowed a minimal amount of intestine to be resected, distinguished between large- and small-intestinal hemorrhage, and eliminated other foci as sites of bleeding.