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Biomedical subjects

A Blair

Publications and source records attributed to A Blair.

At least 55 records · Page 3Linked to original sources

Increased lymphocyte replicative index following 2,4-dichlorophenoxyacetic acid herbicide exposure.

OBJECTIVE: Evaluate peripheral blood lymphocyte proliferation (replicative index:RI) and micronuclei frequency (MF) among 2,4-D herbicide applicators. METHODS: Twelve applicators spraying only 2,4-D provided a blood and urine specimen upon enrollment, several urine samples during the spraying season, and a blood specimen at the study's end. Nine controls provided blood and urine specimens upon enrollment and at the study's end. Gas chromatography/tandem mass spectroscopy determined urinary 2,4-D levels and standard in-vitro assays determined RI and MF scores. Applicator RI and MF were compared before and after spraying and with controls. RESULTS: Applicators contributed 45 urine specimens with concentrations ranging from 1.0 to 1700 (microg 2,4-D/g creatinine/L urine) that logarithmically (In) increased as spraying time increased. Applicator RI increased after spraying (p = 0.016), independent of tobacco and alcohol use, and demonstrated a weak dose-response with increasing urinary 2,4-D levels (p = 0.15). Among 2,4-D applicators, pre-exposure complete blood counts and lymphocyte immunophenotypes were not significantly different from post-exposure measurements. CONCLUSION: Urinary 2,4-D concentration, an exposure biomarker, may be associated with lymphocyte replicative index, a cell proliferation biomarker.

2,4-Dichlorophenoxyacetic Acid↗

Employment as butcher and cancer risk in a record-linkage study from Sweden.

OBJECTIVE: To investigate the risk of cancer among butchers and other meat workers in a large record-linkage study from Sweden. METHODS: The Swedish Cancer Environment Register III contains nationwide data on cancer incidence during 1971-1989 for all residents, by occupation and industry of employment as reported at the 1960 and 1970 censuses. We identified 25,049 men classified as butchers or meat workers at either census. We used as a comparison group the remaining part of the active male population, after exclusion of workers with direct contact with animals. RESULTS: Butchers in the meat industry had a slight increase in the risk of cancer (relative risk [RR] 1.1, 95% confidence interval [CI] 1.0-1.3), which was due to an increased risk of cancers of the oral cavity and pharynx (RR 1.6, 95% CI 1.0-2.7), stomach (RR 1.6, 95% CI 1.1-2.7), larynx (RR 1.4, 95% CI 0.6-3.4), and lung (RR 1.4, 95% CI 1.1-1.9). The risk of stomach cancer was highest during the first 5 years of the study, and among butchers from urban areas. No temporal or geographic variations were seen for lung cancer risk, with elevations restricted to squamous cell carcinoma. An increased risk of stomach, laryngeal and lung cancers was present in butchers and meat workers outside the meat industry. There was no clear indication of an increased risk of other neoplasms. CONCLUSIONS: The increased risk of oral, laryngeal, lung and stomach cancers among Swedish butchers may be at least partly due to confounding by tobacco smoking, alcohol drinking, and other lifestyle factors. However, exposures in the meat industry (e.g., viruses, nitrosamines, polycyclic aromatic hydrocarbons) may contribute the elevated cancer risks.

Adolescent↗

High-resolution HLA class I typing in the CEPH families: analysis of linkage disequilibrium among HLA loci.

The HLA region on the short arm of chromosome 6 (6p21.3) contains the most polymorphic coding sequences in the human genome. High-resolution DNA-based HLA typing of population samples of the polymorphic class I loci, HLA-A, -B, and -C has only recently become feasible. Here, we report molecular HLA typing on family-based samples of European origin (the CEPH repository), which demonstrated very high polymorphism, with 20 A alleles, 38 B alleles and 19 C alleles in the sample of 248 independent haplotypes. In general, allele frequency distributions are consistently more even (lower observed homozygosity statistic) than expected from a past of selective neutrality suggesting a history of balancing selection. This was also true for the class II loci, DRB1, DQA1 and DQB1 in these samples, but not for the DPA1 and DPB1 loci, whose allelic frequency distributions were more skewed (higher observed homozygosity statistic) than expected under a neutral model. Although linkage disequilibrium is a prominent feature across the HLA region, only 19% of the eight locus haplotypes were sampled more than once. The relative age of some of the B alleles could be inferred from the pattern of B-C haplotypic associations. We suggest that the observed patterns of linkage disequilibrium reflect the operation of selection on nearly all HLA alleles.

Alleles↗

Impact on T-cell depletion and CD34+ cell recovery using humanised CD52 monoclonal antibody (CAMPATH-1H) in BM and PSBC collections; comparison with CAMPATH-1M and CAMPATH-1G.

BACKGROUND: Ex vivo T-cell depletion of allogeneic BM (BM) grafts can effectively reduce graft versus host disease (GvHD) and may also apply to transplantation of allogeneic peripheral blood stem cell (PBSC) transplants. METHODS: Here we have evaluated T-cell depletion and progenitor cell recovery by antibody-mediated cells lysis using three CD52 monoclonal antibodies (MAbs) at different concentrations and cell densities. RESULTS: CAMPATH-1M was superior to CAMPATH-1H for T-cell depletion of BM samples. Treatment with CAMPATH-1M resulted in up to 2.55 log depletion of CD3+ cells, with recoveries of >or=45% CD34+ cells, >or=67% CFU-GM and >or=65% BFU-E. CAMPATH-1H treatment resulted in up to 1.64 log depletion of CD3+ cells and similar recoveries of CD34+ cells, CFU-GM and BFU-E as seen with CAMPATH-1M. Depletion of CD19+ cells was similar to that observed for CD3+ cells while natural killer (NK) cells were relatively spared compared with the T and B cell populations. Log depletions of T cells from PBSC, as determined by immunofluorescence studies and limiting dilution analyses, were similar using CAMPATH-1M, -1H, and -1G. There were also no differences in the depletion of CD19+ cells or NK cells using the three MAbs. Similar results were obtained for recoveries of CD34+ cells, CFU-GM and BFU-E using all three MAbs, although the recovery of CD34+ cells using the highest concentration of MAbs was significantly greater in CAMPATH-1H treated samples. Increasing the number of PBSC treated with CAMPATH-1H and -1M had no effect on the log depletion of T, B or NK cells and there were no major differences in the log depletions achieved with CAMPATH-1H or -1M. Likewise, the higher PBSC density had no effect on the recoveries of CD34+ cells or committed progenitors and once again CAMPATH-1H gave similar recoveries to those obtained using CAMPATH-1M. DISCUSSION: Although CAMPATH-1M resulted in greater ex vivo T-cell depletion of BM than CAMPATH-1H, in all other respects, the humanised CAMPATH-1H was just as effective as CAMPATH-1M and -1G.

Alemtuzumab↗

Comparison of industrial hygienists' exposure evaluations for an epidemiologic study.

OBJECTIVES: A study was conducted to determine what level of information is required by industrial hygienists before they can develop exposure estimates comparable with those developed from a more in-depth evaluation. METHODS: Three industrial hygienists evaluated formaldehyde exposures of 300 jobs selected from an earlier epidemiologic study. The jobs were evaluated over the following 6 cycles: (i) job title and industry; (ii) job title, industry, dates; (iii) job and department title and industry; (iv) cycle 3 information with dates; (v) cycle 3 information with a plant report; and (vi) job and department title, industry, dates, and the report. Each hygienist assigned jobs to 1 of 4 exposure categories, which were compared with the categories in the original epidemiologic study. RESULTS: Overall, the mean differences between the hygienists' evaluations and the standard, although small, changed little over the cycles. The kappa statistic was poor to moderate for all the cycles, but the agreement was greater than expected due to chance. There was moderate improvement in overall agreement over the cycles using the weighted kappa statistic, but little improvement in the intraclass correlation coefficients of the hygienists' evaluations, which ranged from 0.4 to 0.5. Department information improved the agreement with the standard by 5--10%, but dates did not the improve agreement. There were some differences by type of plant, job function, exposure level, and date of the estimate. Using a hypothetical exposure-response scenario, this level of misclassification would have resulted in missing an association. CONCLUSIONS: Although there was slight improvement with increasing levels of information, these findings suggest that the subjective categorical assessment of exposures by industrial hygienists will not produce exposure estimates comparable to more in-depth evaluations of exposure.

Epidemiologic Methods↗

Oxidized low density lipoprotein displaces endothelial nitric-oxide synthase (eNOS) from plasmalemmal caveolae and impairs eNOS activation.

Hypercholesterolemia-induced vascular disease and atherosclerosis are characterized by a decrease in the bioavailability of endothelium-derived nitric oxide. Endothelial nitric-oxide synthase (eNOS) associates with caveolae and is directly regulated by the caveola protein, caveolin. In the present study, we examined the effects of oxidized low density lipoprotein (oxLDL) on the subcellular location of eNOS, on eNOS activation, and on caveola cholesterol in endothelial cells. We found that treatment with 10 microgram/ml oxLDL for 60 min caused greater than 90% of eNOS and caveolin to leave caveolae. Treatment with oxLDL also inhibited acetylcholine-induced activation of eNOS but not prostacyclin production. oxLDL did not affect total cellular eNOS abundance. Oxidized LDL also did not affect the palmitoylation, myristoylation or phosphorylation of eNOS. Oxidized LDL, but not native LDL, or HDL depleted caveolae of cholesterol by serving as an acceptor for cholesterol. Cyclodextrin also depleted caveolae of cholesterol and caused eNOS and caveolin to translocate from caveolae. Furthermore, removal of oxLDL allowed eNOS and caveolin to return to caveolae. We conclude that oxLDL-induced depletion of caveola cholesterol causes eNOS to leave caveolae and inhibits acetylcholine-induced activation of the enzyme. This process may be an important mechanism in the early pathogenesis of atherosclerosis.

Animals↗

Occupation and pancreatic cancer risk in Shanghai, China.

BACKGROUND: Any association between occupation and pancreatic cancer risk has not been conclusively demonstrated. A population-based case-control study was conducted to examine occupational risks of pancreatic cancer in Shanghai, China. METHODS: The study included 451 pancreatic cancer patients newly diagnosed in 1990-1993 and 1,552 controls randomly selected from Shanghai residents. Information on a lifetime job history and other factors was obtained in a face-to-face interview. RESULTS: Among men, an increased risk of pancreatic cancer was associated with employment as an electrician (OR = 7.5, CI = 2.6-21.8), and a positive trend in risk with increasing duration of employment was apparent (P for trend = 0.0003). Exposure to electric magnetic fields (EMF) as measured by a job exposure matrix also was associated with an increased risk among electricians. Threefold risks were observed for men with the highest level of intensity and for those with the highest probability of EMF exposure, although women with heavy EMF exposure did not experience increased risk. Among men, elevated risks also were found for metal workers (OR = 2.1, CI = 1.0-4.8); toolmakers (OR = 3.4, CI = 14-7.1); plumbers and welders (OR = 3.0, CI = 1.2-7.5); and glass manufacturers, potters, painters, and construction workers (OR = 2.6, CI = 1.1-6.3). Among women, textile workers experienced an increased risk (OR = 1.4, CI = 0.8-2.6). CONCLUSIONS: Our results suggest that occupations associated with exposures to metal and textile dusts or certain chemicals may increase the risk of pancreatic cancer. The elevated risk among electricians may warrant further study to evaluate the possible role of EMF or other exposures.

Aged↗

Risk of premenopausal breast cancer and patterns of established breast cancer risk factors among teachers and nurses.

BACKGROUND: Contrasting results have been published regarding the risk of breast cancer among teachers and nurses. Confounding by reproductive factors may explain the increased risk observed among women in these occupations as information on those factors were not available in most studies. METHODS: We examined the risk of premenopausal breast cancer among teachers and nurses using occupational histories in a case-control study where information on established risk factors was available. RESULTS: Having ever held a teaching job was not related to breast cancer (OR = 0.74, 95% CI = 0.44-1.28) and women who worked for 10 years or less in this occupation had a non-significant deficit of risk (OR = 0.52, 95% CI = 0.27-1.02). No elevation in risk was found in association with having ever been a nurse (OR = 0.85, 95% CI = 0.45-1.61) or with duration of nursing. Although direct comparison of established risk factors among teachers and nurses and other women in the study showed some evidence of differential distribution, especially when comparing teachers to other women, adjustment for reproductive variables and other breast cancer risk factors did not change the results of this study. CONCLUSION: These findings suggest that teachers and nurses are not at an increased risk of breast cancer. This study also suggests that established risk factors for premenopausal breast cancer may not explain the elevation of risk found in other studies of teachers and nurses. However, this conclusion is limited by the fact that in the present study teachers and nurses had lower than expected breast cancer risk with or without adjustment for established risk factors. Limitations of this study such as low response rates and limited statistical power should be considered in the interpretation of these findings.

Adult↗

Occupational cancer among women: research status and methodologic considerations.

Occupational causes of cancer have not been well-evaluated among women. An increase in the number of women in the work force in jobs with potentially hazardous exposures during the past few decades raises the question as to whether there is a need to enhance our efforts in this area. The inability to evaluate occupational causes of female gynecologic tumors in studies of men, plus the potential for variation in outcome responses between men and women because of gender-based exposure and susceptibility differences, underscore the need for investigations specifically focused on women. Investigations of occupational exposures and cancer risk among women may require design considerations that differ somewhat from studies of men. Issues to consider include the impact of studying outcomes with high survival (e.g., breast cancer), gender-specific exposure patterns and toxicokinetic processing of some chemicals, special limitations in the use of the general population as the referent, and the need to control for established risk factors for gynecologic tumors.

Cohort Studies↗

Characteristics of persons who self-reported a high pesticide exposure event in the Agricultural Health Study.

Characteristics of persons who report high pesticide exposure events (HPEE) were studied in a large cohort of licensed pesticide applicators from Iowa and North Carolina who enrolled in the Agricultural Health Study between December 1993 and December 1995. Fourteen percent reported having "an incident or experience while using any pesticide which caused an unusually high personal exposure. " After taking into account total number of applications made and education, females (OR=0.76), applicators from NC (OR=0.65), and privately licensed applicators (OR=0.65) were less likely to have reported an HPEE. Work practices more common among both private and commercial applicators with an HPEE included delay in changing clothing or washing after pesticide application, mixing pesticide application clothing with the family wash, washing up inside the house after application, applying pesticides within 50 yards of their well, and storing pesticides in the home. Job characteristics more common among those with an HPEE included self-repair of application equipment and first pesticide use more than 10 years in the past. These job characteristics explained much of the difference in reported HPEE between males and females, but not between IA and NC subjects or between commercial or private applicators.

Adult↗

Characteristics of pesticide use in a pesticide applicator cohort: the Agricultural Health Study.

Data on recent and historic pesticide use, pesticide application methods, and farm characteristics were collected from 35,879 restricted-use pesticide applicators in the first 2 years of the Agricultural Health Study, a prospective study of a large cohort of private and commercial licensed pesticide applicators that is being conducted in Iowa and North Carolina. (In Iowa, applicators are actually "certified," while in North Carolina they are "licensed"; for ease of reference the term license will be used for both states in this paper.) Commercial applicators (studied in Iowa only) apply pesticides more days per year than private applicators in either state. When the types of pesticides being used by different groups are compared using the Spearman coefficient of determination (r2), we find that Iowa private and Iowa commercial applicators tend to use the same type of pesticides (r2=0.88). White and nonwhite private applicators tended to use the same type of pesticides (North Carolina r2=0.89), as did male and female private applicators (Iowa r2=0.85 and North Carolina r2=0.84). There was less similarity (r2=0. 50) between the types of pesticides being used by Iowa and North Carolina private applicators. A greater portion of Iowa private applicators use personal protective equipment than do North Carolina private applicators, and pesticide application methods varied by state. This heterogeneity in potential exposures to pesticides between states should be useful for subsequent epidemiologic analyses using internal comparison groups.

Agriculture↗

The adipose tissue to serum dichlorodiphenyldichloroethane (DDE) ratio: some methodological considerations.

Dichlorodiphenyldichloroethane (DDE) adipose tissue level has been regarded as a preferred indicator of accumulated human exposure to DDT; however, blood sera are more feasible to obtain and analyze than adipose tissue samples. Inconsistent and scarce information exists in relation to the adipose tissue/serum DDE ratio. As a part of a hospital-based case-control study performed in Mexico City from 1994 to 1996, 198 paired serum and adipose tissue samples were obtained from 72 women with histologically confirmed breast cancer and 126 women with benign breast disease. Both adipose tissue and serum DDE levels were determined by gas-liquid chromatography and reported as ppb lipid weight (ng/g) as well as wet basis (ng/ml). Results showed that the adipose tissue/serum DDE ratio (ADSE) varies according to the type of information (lipid vs wet basis, arithmetic vs geometric means) used for its estimation. ADSE gets a value near 1 (1.1) only when the geometric DDE levels in lipid basis are used for its estimation. The correlation between DDE serum and adipose tissue levels was found (r=0.364, P<0.001). The ADSE did not vary by disease status, nor was it altered by parity, history of breast-feeding, and other reproductive characteristics. We endorse the use of venipuncture instead of biopsy as a way to estimate DDT body burden levels in further research.

Adipose Tissue↗

Quality control (Part 2). Communication: implementation of the Resident Assessment Instrument (RAI): the benefits of a structured communication plan.

Following a government mandate to use the assessment portion of the Resident Assessment Instrument, S&WCHSC began to integrate the RAI into the care of its Aging Program residents. S&WCHSC have used this as an opportunity to provide a structure for assessment and care planning within the existing philosophy of Patient Focused Care. Implementation of the RAI required the development and implementation of a Communication Plan. An adaptation of a framework, "Effective Strategic Planning for Communications" provided guidelines for assessment of key stakeholders' communication needs.

Aged↗

Expression of HOX genes, HOX cofactors, and MLL in phenotypically and functionally defined subpopulations of leukemic and normal human hematopoietic cells.

To explore the possibility that deregulated HOX gene expression might commonly occur during leukemic hematopoiesis, we compared the relative levels of expression of these and related genes in phenotypically and functionally defined subpopulations of AML blasts and normal hematopoietic cells. Initially, a semi-quantitative RT-PCR technique was used to amplify total cDNA from total leukemic blast cell populations from 20 AML patients and light density cells from four normal bone marrows. Expression of HOX genes (A9, A10, B3 and B4), MEIS1 and MLL was easily detected in the majority of AML samples with the exception of two samples from patients with AML subtype M3 (which expressed only MLL). Low levels of HOXA9 and A10 but not B3 or B4 were seen in normal marrow while MLL was easily detected. PBX1a was difficult to detect in any AML sample but was seen in three of four normal marrows. Cells from nine AML patients and five normal bone marrows were FACS-sorted into CD34+CD38-, CD34+CD38+ and CD34-subpopulations, analyzed for their functional properties in long-term culture (LTC) and colony assays, and for gene expression using RT-PCR. 93 +/- 14% of AML LTC-initiating cells, 92 +/- 14% AML colony-forming cells, and >99% of normal LTC-IC and CFC were CD34+. The relative level of expression of the four HOX genes in amplified cDNA from CD34- as compared to CD34+CD38- normal cells was reduced >10-fold. However, in AML samples this down-regulation in HOX expression in CD34- as compared to CD34+CD38- cells was not seen (P < 0.05 for comparison between AML and normal). A similar difference between normal and AML subpopulations was seen when the relative levels of expression of MEIS1, and to a lesser extent MLL, were compared in CD34+ and CD34- cells (P < 0.05). In contrast, while some evidence of down-regulation of PBX1a was found in comparing CD34- to CD34+ normal cells it was difficult to detect expression of this gene in any subpopulation from most AML samples. Thus, the down-regulation of HOX, MEIS1 and to some extent MLL which occurs with normal hematopoietic differentiation is not seen in AML cells with similar functional and phenotypic properties.

ADP-ribosyl Cyclase↗

Occupational physical activity and non-Hodgkin's lymphoma.

PURPOSE: The purpose of this study was to evaluate the role of physical activity in the development of non-Hodgkin's lymphoma (NHL). METHODS: Incident NHL cases and population-based controls were identified from three case-control studies conducted in four midwestern states: Iowa, Kansas, Minnesota, and Nebraska. A total of 1177 cases (993 men, 184 women) and 3625 controls (2918 men, 707 women) were interviewed. Usual occupation (all states) and lifetime occupational histories (Iowa and Minnesota only), obtained from interviews, were classified for energy expenditure (EE) and sitting time. Odds ratios (OR) and 95% confidence intervals were calculated comparing moderate and high activity levels with sedentary levels. RESULTS: There was no evidence of an association between NHL and occupational physical activity measured either by EE or sitting time. Among men, the OR associated with usual occupation moderate and high EE were 1.1 and 1.0, respectively. For sitting time, the OR were also 1.1 and 1.0 for moderate and high activity, respectively. Among women, slight nonsignificant elevations in risk of NHL were observed among the high energy level and high activity sitting categories. The trends were not significant. There was no evidence of confounding or effect modification by vital status, hair dye use, or solvent exposure. Among subjects with lifetime occupational histories, there were no significant increases or trends for cumulative or average EE or sitting time. There was no association between occupational physical activity and NHL. CONCLUSION: Research on nonoccupational physical activity, which in the U.S. is likely the more important component of daily activity than occupational activity, may still be warranted given the laboratory evidence linking physical activity and immune function, an important factor in the etiology of NHL.

Adult↗

Exposure of farmers to phosmet, a swine insecticide.

OBJECTIVES: The goal of this study was to measure dermal and inhalation exposures to phosmet during application to animals and to identify what determinants of exposure influence the exposure levels. METHODS: Ten farmers were monitored using dermal patches, gloves, and air sampling media during normal activities of applying phosmet to pigs for insect control. Exposures were measured on the clothing (outer), under the clothing (inner), on the hands, and in the air. Possible exposure determinants were identified, and a questionnaire on work practices was administered. RESULTS: The geometric mean of the outer exposure measurements was 79 microg/h, whereas the geometric mean of the inner exposure measurements was 6 microg/h. The geometric mean for hand exposure was 534 microg/h, and the mean air concentration was 0.2 microg/m3. Glove use was associated with the hand and total dermal exposure levels, but no other determinant was associated with any of the exposure measures. The average penetration through the clothing was 54%, which dropped to 8% when the farmers wearing short sleeves were excluded. The farmers reported an average of 40 hours a year performing insecticide-related tasks. CONCLUSIONS: Farmers who applied phosmet to animals had measurable exposures, but the levels were lower than what has been seen in other pesticide applications. Inhalation exposures were insignificant when compared with dermal exposures, which came primarily from the hands. Clothing, particularly gloves, provided substantial protection from exposures. No other exposure determinant was identified.

Animal Husbandry↗

Occupational cancer epidemiology in the coming decades.

Occupational studies have identified many of the established chemical carcinogens. Studies in the next millennium will be needed to identify the hazardous agents in occupations known to have high cancer rates, to assess human risks from animal carcinogens that have not been well evaluated epidemiologically, to provide information on women and minorities, to evaluate interactions with genetic factors and other risk factors, to contribute to our understanding of risks from the spread of chemicals from the workplace to the general environment, and to identify mechanisms of cancer. The traditional retrospective cohort design will be insufficient to meet these needs. Population-based case-control, nested case-control, prospective cohorts, and cross-sectional designs will assume more important roles because of the need to collect information on nonoccupational risk factors and biological tissues. Improvement in the assessment of quantitative exposures is needed for the efficient evaluation of interactions between occupational exposures, genetic factors, and nonoccupational exposures.

Carcinogens↗