The tight interallelic positional coincidence that distinguishes T-cell receptor Jalpha usage does not result from homologous chromosomal pairing during ValphaJalpha rearrangement.

The T-cell receptor (TCR) alpha locus is thought to undergo multiple cycles of secondary rearrangements that maximize the generation of alphabeta T cells. Taking advantage of the nucleotide sequence of the human Valpha and Jalpha segments, we undertook a locus-wide analysis of TCRalpha gene rearrangements in human alphabeta T-cell clones. In most clones, ValphaJalpha rearrangements occurred on both homologous chromosomes and, remarkably, resulted in the use of two neighboring Jalpha segments. No such interallelic coincidence was found for the position of the two rearranged Valpha segments, and there was only a loose correlation between the 5' or 3' chromosomal position of the Valpha and Jalpha segments used in a given rearrangement. These observations question the occurrence of extensive rounds of secondary Valpha-->Jalpha rearrangements and of a coordinated and polarized usage of the Valpha and Jalpha libraries. Fluorescence in situ hybridization analysis of developing T cells in which TCRalpha rearrangements are taking place showed that the interallelic positional coincidence in Jalpha usage cannot be explained by the stable juxtaposition of homologous Jalpha clusters.

Clinical relevance of direct quantification of pp65 antigenemia using flow cytometry in solid organ and stem cell transplant recipients.

A total of 1,305 blood samples from 85 solid organ transplant (SOT) recipients and 25 stem cell transplant (SCT) recipients at risk for cytomegalovirus (CMV) infection were prospectively collected and tested using the shell vial assay (SVA) and a leukocytic qualitative PCR (q-PCR). Of these, 462 specimens were further tested by direct quantification of CMV antigenemia by flow cytometry (FC-Ag), 125 were tested with a quantitative competitive PCR, and 200 were tested for pp65 antigenemia using the slide method (S-Ag). Laboratory data were statistically analyzed according to the presence of CMV-related symptoms. In SOT and SCT recipients, active CMV infection occurred in 63.5 and 36%, respectively, and CMV disease occurred in 53 and 24%, respectively. FC-Ag results correlated better with q-PCR and S-Ag than with SVA. The first test found to be positive during follow-up was FC-Ag in 73% of cases. In SOT recipients, FC-Ag showed the highest sensitivity and negative predictive value for the diagnosis of any grade of CMV disease. For FC-Ag, the threshold beyond which CMV disease was highly probable seemed to lie at 0.20% positive polymorphonuclear leukocytes. FC-Ag appears to be a useful test for the early detection of CMV infection and the prediction of CMV disease.

Associations between heart rate and other risk factors in a large French population.

OBJECTIVES: In a large general French population of 100,000 subjects, the relationship of resting heart rate with age, gender, demographic parameters, physical activity and classical risk factors was evaluated. POPULATION AND METHODS: A population composed of all the subjects who had a free health check-up at the IPC Centre between 1992 and 1995 (62,353 men and 35,371 women) was analysed. Heart rate was considered either as a continuous parameter or as a qualitative parameter. The study population was divided into four heart rate classes: < 65, 65-74, 75-84 and > or = 85 beats/min. RESULTS: Women had significantly higher heart rate values than men, and this gender difference was constant in the different age groups. In both genders, heart rate was positively associated with blood pressure, triglycerides, glycaemia and physical inactivity, and negatively with body height Heart rate was also correlated with total cholesterol but only in men. The only factor having opposite effects on heart rate in men and women was tobacco smoking (positive in men and negative in women). Among untreated hypertensive men, 21.3% had a heart rate > or = 85 beats/min compared with only 4.0% among normotensive men. In women, these percentages were 23.6 and 7.6%, respectively. Subjects with untreated mild hypertension or uncontrolled treated hypertension also showed increased rates of tachycardia compared to normotensives. CONCLUSIONS: The present analysis, performed in a large French population, shows that high heart rate is associated with several other risk factors, especially hypertension, suggesting that tachycardic subjects have a high risk profile.

Sinonasal cancer and occupational exposure to textile dust.

Data from a case-control study conducted at 27 hospitals in France in 1986-88 were analyzed to examine the association between exposure to textile dust and sinonasal cancer. The study included 207 cases and 409 controls. Detailed information on occupational history and other potential risk factors for sinonasal cancer was collected. Exposure to textile dust (probability and level of exposure, type of textile fiber) was assessed by an expert in industrial hygiene. Among women, exposure to textile dust was associated with an elevated risk of squamous cell carcinoma (odds ratio (OR) = 2.45, 95% confidence interval (CI) = 0.85-7.06, nine exposed cases) and adenocarcinoma (OR = 3.70, 95% CI = 0.56-24.4, three exposed cases). For squamous cell carcinomas, the risk increased with the duration and the level of exposure (P < 0.05): the ORs for the low, medium, and high level of cumulative exposure were 1.00 (95% CI = 0.10-9.43), 2.43 (95% CI = 0.54-11.1), and 3.57 (95% CI = 0.92-13.8), respectively. There was also a limited evidence of an excess risk of squamous cell carcinomas among men exposed to high levels of textile dust (OR = 2.18, 95% CI = 0.65-7.30, four exposed cases). Because of the strong association between wood-dust exposure and adenocarcinoma, an independent effect of textile dust on this type of cancer could not be studied among men. The risks associated with the different types of textile fibers (cotton, wool, and synthetic fibers) were similar and the results did not permit to incriminate a particular type of textile.

Laryngeal and hypopharyngeal cancer and occupation: results of a case control-study.

OBJECTIVES: To ascertain whether certain occupations are associated with laryngeal or hypopharyngeal cancer. METHODS: A hospital based case-control study was carried out in 15 hospitals in France. It included 528 male cases diagnosed between January 1989 and April 1991, and 305 male controls with various other types of cancer. Interviews were carried out to obtain lifetime job histories and information on potential confounders. Logistic regression was used to compute the odds ratios (OR) for each of about 80 occupations and industries. RESULTS: There was an excess risk of laryngeal and hypopharyngeal cancer among service workers (OR 2.2, 95% confidence interval (95% CI) 1.3 to 3.9), agricultural and animal husbandry workers (OR 1.6, 95% CI 0.9 to 2.8), miners and quarrymen (OR 2.0, 95% CI 0.9 to 4.3), plumbers and pipe fitters (OR 2.6, 95% CI 0.8 to 8.1), glass formers and potters (OR 4.3, 95% CI 1.0 to 18) transport equipment operators (OR 1.5, 95% CI 1.0 to 2.5), and unskilled workers (OR 1.7, 95% CI 1.0 to 2.9). Analysis by industrial branch showed an excess risk for coal mining (OR 2.1, 95% CI 1.1 to 4.1), manufacture of metal products (OR 1.9, 95% CI 1.0 to 3.3), and administration and sanitary services (OR 1.7, 95% CI 1.1 to 2.5). CONCLUSION: These results suggest that occupational exposure might have a role in generating laryngeal and hypopharyngeal cancer, and indicate the need for further evaluation of these findings, an for the identification of the carcinogens which might account for the excess risks found for certain occupations.

Sinonasal cancer and occupation. Results from the reanalysis of twelve case-control studies.

A pooled reanalysis of twelve case-control studies on sinonasal cancer and occupation from seven countries was conducted in order to study associations with occupations other than wood- and leather-related occupations. The pooled data set included a total of 930 cases (680 men and 250 women) and 3,136 controls (2,349 men and 787 women). All the studies included a detailed occupational history for cases and controls. Each job was coded using the same classifications for occupation and industry. Two approaches were used in the analysis: systematic analysis of occupations; a priori analysis using a preestablished list of occupations and industries. The results confirmed associations observed in several studies not included in this analysis. For agricultural workers, significant excesses were observed for squamous cell carcinoma among women (OR = 1.69) and men (OR = 3.72 for ten years or more of employment as an orchard worker), and adenocarcinomas among men (OR = 2.98 for ten years or more of employment). Associations with textile occupations were observed for adenocarcinoma among women (OR = 2.60) and squamous cell carcinoma among men (OR = 5.09 for fiber preparers, 3.01 for bleachers). Elevated risks for both histologic types were observed among men employed in food manufacturing (OR = 3.25, adenocarcinoma), or as food preservers (OR = 13.9, squamous cell carcinoma), and among men employed as cooks (OR = 1.99, squamous cell carcinoma). A positive association with squamous cell carcinoma was observed for male transport equipment operators (OR = 1.21), and also with adenocarcinoma for male motor-vehicle drivers (OR = 2.50). A number of other associations were observed in the systematic analysis.

Sinonasal cancer and occupational exposure to formaldehyde and other substances.

A case-control study of cancer of the nose and paranasal sinuses was conducted in France to determine whether occupational exposure to formaldehyde was associated with an increased risk of sinonasal cancer. Exposures to 14 other substances or groups of substances were also studied (wood dust, leather dust, textile dust, flour dust, sugar dust, coal/coke dust, nickel compounds, chromium compounds, chromium VI, welding fumes, soldering fumes, cutting oils, paints and lacquers, glues and adhesives). Cases (n = 207) and controls (n = 409) were interviewed to obtain detailed information on job history and other potential risk factors for sinonasal cancer. In addition, a questionnaire specially designed for this study was used to help assess exposures to formaldehyde and other substances of interest. The questionnaires were translated into history of occupational exposure by an expert in industrial hygiene, without knowledge of case-control status. Several exposure variables (lifetime average level, duration, cumulative level) were used to describe the risk related to exposure to formaldehyde. Potential confounding factors (occupational and non-occupational) were examined and adjusted for when necessary. No significant association was found between exposure to formaldehyde and squamous-cell carcinomas of the sinonasal cavities. Because of the strong association between exposure to wood dust and nasal adenocarcinoma, it was not possible to assess an independent effect of formaldehyde on this type of cancer. However, among males exposed to medium or high levels of wood dust, the risk of adenocarcinoma associated with formaldehyde was significantly elevated for the highest exposure categories for average level (OR = 5.3, 95% confidence interval = 1.3-22.2), cumulative level (OR = 6.9, 95% CI = 1.7-28.2) and duration of exposure (OR = 6.9, 95% CI = 1.7-27.8). Although a residual confounding effect of wood dust could not be excluded, this study suggests that exposure to both formaldehyde and wood dust may increase the risk of nasal adenocarcinoma, by comparison with the risk due to wood dust alone. This study also indicated an increased risk among males who had been exposed to glues and adhesives, for all histologic types, which was not explained by a confounding effect of paints and lacquers, wood dust or formaldehyde. No other significant association was observed.

Low-back pain in commercial travelers.

The role of occupational environment in the occurrence of low-back pain was analyzed for 1719 commercial travelers (1376 men and 343 women). At the beginning of the study (T0) the group was interviewed to determine current lifestyle and occupational factors associated with low-back pain during the previous 12 months. Twelve months later (at T1), a subsample of 1118 persons (893 men, 225 women) was reinterviewed to study the association between the incidence of low-back pain during the year of follow-up and the risk factors at T0. At T0 low-back pain was significantly related with time spent driving a car at work, comfort of the car seat, carrying loads during work, standing for long periods at work, smoking, and psychosomatic factors. At T1 driving 10 h/week or more, seat comfort, and psychosomatic factors were associated with first occurrence of low-back pain.

Occupational risk factors for sinonasal cancer: a case-control study in France.

A case-control study was conducted in France to examine occupational risk factors for sinonasal cancer; 207 cases and 409 controls were included in the study. Detailed information was collected on occupational history and other potential risk factors for nasal cancer. Results are presented for three histologic types: adenocarcinoma, squamous cell carcinoma, and others. Among males, the risk of adenocarcinoma was significantly elevated for cabinetmakers (odds-ratio = 35.4, 95% confidence interval = 18.1-69.3), carpenters and joiners (OR = 25.2, 95% CI = 14.6-43.6), and wood-working machine operators (OR = 7.4, 95% CI = 3.4-15.8), whereas the odds-ratios were less than 1 for loggers and wood preparation workers. Odds-ratios associated with cabinetmakers (OR = 11.2, 95% CI = 2.7-45.9)) and carpenters and joiners (OR = 5.8, 95% CI = 1.8-18.6) were also significantly elevated for the other-histologic-types category. Significant excesses in risk of squamous cell cancer were noted for "bakers, pastry cooks, grain millers" (OR = 3.9, 1.2-12.8), construction workers (OR = 3.7, 95% CI = 1.7-8.0), and carpenters and joiners having worked for at least 15 years in the wood manufacturing industry (OR = 8.1, 95% CI = 1.3-50.3). Among females, a significant increase in risk of squamous cell carcinoma (OR = 9.5, 95% CI = 1.7-54.1) and a moderate increase in risk of adenocarcinoma (OR = 4.0, 95% CI = 0.7-23.5) was observed for textile workers. Elevated risks of squamous cell cancer were noted for farm workers of both sexes (males: OR = 2.2, 95% CI = 1.1-4.4; females: OR = 4.9, 95% CI = 1.0-24.9).