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Biomedical subjects

L M Brown

Publications and source records attributed to L M Brown.

At least 19 recordsLinked to original sources

Pesticides and other agricultural risk factors for non-Hodgkin's lymphoma among men in Iowa and Minnesota.

Data from an in-person interview study of 622 white men with newly diagnosed non-Hodgkin's lymphoma and 1245 population-based controls in Iowa and Minnesota were used to measure the risk associated with farming occupation and specific agricultural exposures. Men who ever farmed were at slightly elevated risk of non-Hodgkin's lymphoma (odds ratio = 1.2, 95% confidence interval = 1.0-1.5) that was not linked to specific crops or particular animals. Elevated risks were found, with odds ratio generally 1.5-fold or greater, for personal handling, mixing, or application of several pesticide groups and for individual insecticides, including carbaryl, chlordane, dichlorodiphenyltrichloroethane, diazinon, dichlorvos, lindane, malathion, nicotine, and toxaphene. Associations were generally stronger for first use prior to 1965 than more recently, and when protective clothing or equipment was not used. Small risks were associated with the use of the phenoxyacetic acid herbicide 2,4-dichlorophenoxyacetic acid, but the risks did not increase with latency or failure to use protective equipment. Exposure to numerous pesticides poses problems of interpreting risk associated with a particular chemical, and multiple comparisons increase the chances of false-positive findings. In contrast, nondifferential exposure misclassification due to inaccurate recall can bias risk estimates toward the null and mask positive associations. In the face of these methodological and statistical issues, the consistency of several findings, both within this study and with observations of others, suggests an important role for several insecticides in the etiology of non-Hodgkin's lymphoma among farmers.

Adult

Smoking and risk of leukemia.

The relation between tobacco use and leukemia was evaluated in a population-based case-control study of 578 white men with leukemia and 820 controls conducted in Iowa and Minnesota during 1981-1984. Risks were significantly elevated for all leukemia (odds ratio (OR) = 1.4) and chronic lymphocytic leukemia (OR = 1.6) for both tobacco users and cigarette smokers. There were significantly elevated risks for cigarette smokers of longest duration for all leukemia (OR = 1.6), chronic myelogenous leukemia (OR = 3.3), and chronic lymphocytic leukemia (OR = 1.6). Thus, the findings of this study provide additional support for an association between smoking and the risk of several types of leukemia.

Adult

Smoking and risk of non-Hodgkin's lymphoma and multiple myeloma.

Population-based case-control interview studies of 622 White men with non-Hodgkin's lymphoma and 820 controls from Iowa and Minnesota (United States) and 173 White men with multiple myeloma and 452 controls from Iowa offered the opportunity to investigate the relationship of these cancers with smoking. Risks were significantly elevated for all lymphoma (odds ratio [OR] = 1.4), high-grade lymphoma (OR = 2.3), and unclassified lymphoma (OR = 2.8) for cigarette smokers. Dose-response gradients were not seen with intensity of cigarette use, but risks for these subtypes were greatest for cigarette smokers of longest duration. Similar elevations in risks were seen for tobacco users. The risk of multiple myeloma was not significantly elevated for either tobacco users or cigarette smokers. The findings from this study confirm the lack of an association between smoking and multiple myeloma and provide some support for an association between tobacco use and certain subtypes of non-Hodgkin's lymphoma.

Case-Control Studies

Alcohol consumption and risk of leukemia, non-Hodgkin's lymphoma, and multiple myeloma.

Population-based case-control interview studies of white men, 578 with leukemia, 622 with non-Hodgkin's lymphoma, and 820 controls from Iowa and Minnesota and 173 with multiple myeloma and 452 controls from Iowa, offered the opportunity to investigate the relationship of these cancers with alcohol consumption. Although drinkers had non-significantly elevated risks for specific subtypes of leukemia (acute lymphocytic leukemia (OR = 3.0), myelodysplasia (OR = 1.6), and other leukemia (OR = 1.5)) and multiple myeloma (OR = 1.3), there were no statistically significant findings and no dose-response gradients with amount of alcohol consumed. Thus, these data suggest that alcohol is not an important contributor to the etiology of lymphatic and hematopoietic tumors.

Alcohol Drinking

Hair dye use and multiple myeloma in white men.

In recent reports, multiple myeloma has been linked to use of hair coloring products containing mutagenic and carcinogenic chemicals. A population-based case-control study in Iowa of 173 White men with multiple myeloma and 650 controls obtained information on hair dye use. Risk of multiple myeloma was significantly elevated (OR = 1.9) among hair dye users and was greatest among those using hair dyes at least once a month for a year or more (OR = 4.3). These data, along with results from other studies, suggest that use of hair dyes contributes to the development of multiple myeloma.

Adult

Stimulation of N-methyl-D-aspartate receptor-mediated calcium entry into dissociated neurons by reduced and oxidized glutathione.

The effects of GSH (gamma-glutamylcysteinylglycine) and GSSG on intracellular calcium levels ([Ca2+]i) were investigated using fura-2-loaded dissociated brain cells from newborn rat pups. Both produced concentration-dependent increases in [Ca2+]i (EC50 values of 914.3 +/- 190.5 and 583.0 +/- 97.2 microM for GSH and GSSG, respectively), similar to that observed with N-methyl-D-aspartate (NMDA) and other agonists at the NMDA receptor. Maximum response (expressed as percentage change in [Ca2+]i relative to basal) was significantly greater for GSSG (37.5 +/- 1.6%) than for GSH (25.3 +/- 1.6%). The response to both agents was prevented or reversed by competitive (100 microM) (-)-2-amino-5- phosphonovalerate and noncompetitive (400 nM) MK-801 or 1.0 mM Mg2+ antagonists of NMDA receptor-mediated calcium entry, even at concentrations of GSH and GSSG normally producing maximal response. The idea that these effects are mediated, at least in part, by interaction with the NMDA receptor was supported by the effects of GSH and GSSG on the binding of the NMDA receptor ligand [3H]CGP-39653 to membranes isolated from hippocampal and cortical homogenates. Both GSH and GSSG displaced bound [3H]CGP-39653, with IC50 values of 0.93 +/- 0.18 and 11.02 +/- 1.22 microM, respectively, and produced an increase in the apparent Kd of binding (control, 8.92 +/- 0.83 nM, and GSH, 13.31 +/- 1.19 nM; control, 11.59 +/- 0.35 nM, and GSSG, 18.73 +/- 0.66 nM). However, both also produced modest reductions in Bmax (control, 1265 +/- 69 fmol/mg of protein, and GSH, 901 +/- 73 fmol/mg of protein; control, 1068 +/- 30 fmol/mg of protein, and GSSG, 730 +/- 18 fmol/mg of protein) and Hill slopes (GSH, 0.66 +/- 0.02; GSSG, 0.62 +/- 0.04). This suggests complex kinetics for the interaction of GSH and GSSG with the NMDA receptor. Taken together, the results suggest the potential for modulation of the NMDA receptor complex by GSH and GSSG.

2-Amino-5-phosphonovalerate

Comparability of data obtained from farmers and surrogate respondents on use of agricultural pesticides.

Information from surrogates is increasingly being used in case-control studies to evaluate cancer risks from pesticides; however, little is known about the quality of this type of information. To address this concern, the authors compared interview data collected in 1987 from 95 male Iowa farmers and their wives or other surrogates on the use of specific agricultural pesticides. Agreement between direct and surrogate interviews was excellent (83-100%) for responses to dichotomous (yes/no) questions regarding past agricultural use of specific pesticides. Although there were more discrepancies for detailed questions (e.g., the number of days per year on which each pesticide was handled), responses from spouses appear to be adequate for epidemiologic studies of pesticides and cancer.

Adult

The effects of chronic ethanol exposure on N-methyl-D-aspartate-stimulated overflow of [3H]catecholamines from rat brain.

The effects of acute and chronic ethanol administration on N-methyl-D-aspartate-stimulated catecholamine overflow were examined. Three groups of male Sprague-Dawley rats were used. The first group received a chronic liquid diet containing ethanol (37%) for 3 weeks. The second group was pair-fed a liquid diet with dextrin substituted for ethanol isocalorically. The third group received Purina rat lab chow and water ad libitum. N-methyl-D-aspartate-stimulated [3H]catecholamine overflow from brain tissue slices was determined. N-methyl-D-aspartate (50-2000 microM) produced a concentration-dependent increase in [3H]norepinephrine overflow from cortical and hippocampal slices with no significant alteration of the response following chronic ethanol treatment. [3H]Dopamine overflow from striatal slices of the chronic ethanol group was significantly different at 1000 microM N-methyl-D-aspartate. The response of the chronic ethanol-treated group at the 1000 microM N-methyl-D-aspartate concentration was 30% and 40% lower than the pair-fed and ad libitum controls, respectively. Ethanol when added in vitro (30-200 mM) produced a concentration-dependent inhibition of N-methyl-D-aspartate (150 microM) stimulated efflux in all brain regions, and chronic ethanol treatment did not alter the inhibitory response. These results indicate an apparant lack of adaptation in N-methyl-D-aspartate-stimulated transmitter release following chronic ethanol treatment in this particular paradigm.

Animals

Testicular cancer in young men and parental occupational exposure.

To investigate whether parental occupation, especially during the 12 month period before birth, could be responsible for elevated rates of testicular cancer in young men, we used data from a case-control study of 223 cases and 212 controls conducted in the Washington, DC area. For all histologic types of testicular cancer combined, no significant associations were found for specific occupations, nor for the broad occupational categories of professional, other white collar, or blue collar workers. However, for cases with seminomas, excess risks were seen for those with parents employed in the following occupations: mothers in health-related occupations, O.R. = 4.6 (1.1-19.1), and fathers working in automobile service stations, O.R. = 4.0 (0.6-24.5), manufacturing industries, O.R. = 2.2 (1.0-4.2), and aircraft production and maintenance, O.R. = 5.3 (0.7-24.1). Although these findings for seminoma are intriguing, they do not explain the increase of testicular cancer in young men.

Adolescent

Cryopreservation and long-term liquid nitrogen storage of peripheral blood mononuclear cells for flow cytometry analysis: effects on cell subset proportions and fluorescence intensity.

The effect of cryopreservation and long-term liquid nitrogen storage on peripheral blood mononuclear cell (PBMC) subsets was prospectively analyzed using monoclonal antibodies and flow cytometry. Brief cryopreservation did not significantly alter the proportion of positively stained cells for CD3+, CD4+, CD8+, CD14+, CD16+, and CD19+ cells. A small but statistically significant increase in the proportion of positive cells was observed for HLA-DR+ and HLe-1+ cells. Brief cryopreservation was associated with a decrease in the mean fluorescence intensity (MFI) values for CD3+, CD4+, and CD8+ cells; an increase in MFI values for CD14+ and HLA-DR+ cells; and no change for CD16+, CD19+, and HLe-1+ cells. There was no significant change in the proportion of CD3+, CD4+, or CD16+ cells during 20 months of storage in liquid nitrogen. Small but statistically significant decreases in the proportion of CD8+ and CD19+ cells were observed over the same interval, and the proportion of CD14+ cells (monocytes) was highly variable. Chronologic changes in fluorescence intensity during long-term storage were observed for all cell subsets except CD16+ and CD19+ cells. Cryopreservation is a valuable technique for long-term storage of viable cells. For many laboratory applications, the small changes noted in the present study will have no practical importance. However, for clinical and epidemiological investigations encompassing large numbers of samples, statistical techniques to adjust for small changes during storage should be considered.

Antigens, CD

Some observations on variations in filament overlap in tetanized muscle fibres and fibres stretched during a tetanus, detected in the electron microscope after rapid fixation.

Anomalous tension development which would not be predicted from the descending limb of the length-tension curve occurs during prolonged tetani and after stretch during a tetanus. Variations in filament overlap might account for all or part of the tension enhancement. Fibres isolated from frog skeletal muscle were rapidly fixed during a tetanus with mercuric chloride in ethanol and chloroform so that the correct alignment of the filaments in the overlap zones was preserved. The fibres were examined in polarized light with compensation, and in the electron microscope. There were variations in striation spacing along the length of the fibres, and severe shortening with contraction bands near the tendon insertions, confirming observations made by others on live fibres. Many variations in filament overlap which would not be detectable by light microscopy or laser diffraction were seen in the electron microscope. In a pilot study we measured differences in the width of the overlap zones between half-sarcomeres in a small area and within individual half-sarcomeres. In the latter case the variations were greater in a fibre which developed creep of tension and one which did not. Even greater variations were seen in three fibres stretched during a tetanus, and, in two of these, there were some grossly elongated half-sarcomeres in which the filaments had pulled out of the overlap zones, leaving gaps.

Animals

T cell subsets in healthy black smokers and nonsmokers. Evidence for ethnic group as an important response modifier.

The influence of cigarette smoking on T cell subsets has been studied in white subjects, but comparable data are not available for blacks. We analyzed peripheral blood mononuclear cell subsets in a population-based, stratified, random sample of healthy black adults using monoclonal antibodies and flow cytometry. The study population consisted of 94 men and 79 women, including 73 smokers (CS) and 100 nonsmokers (NS). Cigarette smoking was associated with a significant elevation in leukocyte (WBC) count (CS 7,270 +/- 230 cells/mm3 versus NS 6,260 +/- 160 cells/mm3; p = 0.001), although WBC counts for both groups were substantially lower than those reported for white smokers and nonsmokers. Smokers had a significantly lower proportion of CD4+ cells than nonsmokers (CS 55.4 +/- 0.9% versus NS 58.7 +/- 0.9; p = 0.01), adjusting for age and gender. No significant smoking-related changes were observed for CD8+ cells, the CD4/CD8 ratio, or total T cells (CD3+), monocytes (CD14+), or natural killer cells (CD16+). Among black smokers, a significant dose-related decrease in CD4+ cells was observed as the number of cigarettes smoked per day increased. Among black exsmokers, the level of WBC and CD4+ cells returned to the level observed in never smokers within 2 to 5 yr after smoking cessation. These results contrast sharply with the previously reported increase in CD4+ cells and decrease in natural killer cells associated with cigarette smoking in whites. The data suggest that the immunologic effects of cigarette smoking may be significantly modified by ethnic characteristics.

Adult

Intake of tapwater and total water by pregnant and lactating women.

BACKGROUND: Despite theoretically higher requirements for water due to physiologic demands of pregnancy and lactation, little is known of actual ranges of intake in pregnant and lactating women. METHODS: Population-based estimates of total water and tapwater intake in women of reproductive age were derived using data from the 1977-78 USDA Nationwide Food Consumption Survey. Three-day average intakes were calculated for 188 pregnant women, 77 lactating women, and 6,201 non-pregnant, non-lactating control women. RESULTS: Total water intake (mean +/- SD) was 1,940 +/- 686 g/day (median 1,835) for control women, 2,076 +/- 743 g/day (median 1,928) for pregnant women and 2,242 +/- 658 g/day (median 2,164) for lactating women. Tapwater intake was 1,157 +/- 635 g/day (median 1,065) for control women, 1,189 +/- 699 g/day (median 1,063) for pregnant women, and 1,310 +/- 591 g/day (median 1,330) for lactating women. Total water intake was equal to or greater than 3,000 g/day among 7 percent of control women, 11 percent of pregnant women, and 13 percent of lactating women. Tapwater intake was equal to or greater than 2,000 g/day among 10 percent of control women, 15 percent of pregnant women, and 8 percent of lactating women. CONCLUSIONS: These results should be useful in estimating amounts of nutrients and toxic substances that women of reproductive age obtain through the water supply.

Adolescent

Magnetoencephalographic localization of interictal spike sources. Case report.

The reliability of localization of interictal spike sources using magnetoencephalography (MEG) was examined by repeated measurements in a patient with temporal lobe epilepsy. During two preoperative recording sessions, the estimated sources, projected onto magnetic resonance images of the patient's brain, were found to lie less than 1 cm apart within the area subsequently resected. The MEG localization was in close agreement with intraoperative cortical recordings.

Adult

Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and Minnesota.

Mortality surveys and death certificate studies have suggested an association between leukemia and farming. To investigate whether exposure to carcinogens in an agricultural setting is related to risk of leukemia, the authors conducted a population-based case-control interview study of 578 white men with leukemia and 1245 controls living in Iowa and Minnesota. Consistent with recent mortality studies, there were slight, but significant, elevations in risk for all leukemia [odds ratio (OR) 1.2] and chronic lymphocytic leukemia (OR 1.4) for farmers compared to nonfarmers. There were no significant associations with leukemia for exposure to specific fungicides, herbicides (including 2,4-D and 2,4,5-T), or crop insecticides. However, significantly elevated risks for leukemia of greater than or equal to 2.0 were seen for exposure to specific animal insecticides including the organophosphates crotoxyphos (OR 11.1), dichlorvos (OR 2.0), and famphur (OR 2.2) and the natural product pyrethrins (OR 3.7) and the chlorinated hydrocarbon methoxychlor (OR 2.2). There were also smaller, but significant, risks associated with exposure to nicotine (OR 1.6) and DDT (OR 1.3). This finding of elevated risks for insecticides used on animals deserves further evaluation.

Agricultural Workers' Diseases

Amorphisation of MgO single crystal specimens prepared by ion milling for transmission electron microscopy studies.

Single crystal MgO specimens having low load Vickers indentations were thinned in an ion milling machine employing a single ion gun, and their characteristics were investigated with optical microscopy and high voltage electron microscopy (HVEM). It was found that the state of cleanliness of the specimen chamber of the ion milling machine had a very marked influence on the quality of the thinned specimens. If the specimen chamber was not well cleaned before ion milling a fresh specimen, the latter tended to show amorphisation due to the deposition on the specimen of the debris left in the chamber from the previously ion-milled specimens. Such observations were made from MgO specimens ion milled in several different types of commercial ion milling machine employing a single gun. It is proposed that to obtain good-quality ion milled TEM specimens, it is important to clean the specimen chamber thoroughly prior to milling.

Magnesium Oxide

T-cell subsets in healthy teenagers: transition to the adult phenotype.

Little is known about the normal range and variability of T-cell subsets in older children. We analyzed peripheral blood mononuclear cell subsets in 112 healthy children, ages 12-19 years (mean +/- SD: 15.4 +/- 1.9 years), using monoclonal antibodies and flow cytometry. The study population included 28 blacks and 84 whites, with 59 boys and 53 girls. The mean +/- SD cell subset values were: CD3+ T cells, 74.0 +/- 7.8%; CD4+ helper-inducer T cells, 46.8 +/- 6.9%; CD8+ suppressor-cytotoxic T cells, 27.3 +/- 5.7%; CD4:CD8 helper:suppressor ratio, 1.81 +/- 0.57; CD16+ natural killer cells, 4.4 +/- 3.1%; CD19+ B cells, 10.0 +/- 5.3%; CD14+ monocytes, 20.0 +/- 6.5%; and HLA-DR cells, 15.4 +/- 4.8%. Overall, boys had a higher proportion of HLA-DR+ cells than girls, attributable to an increase in CD19+ B cells. Blacks tended to have a higher proportion of HLA-DR+ cells than whites, apparently due to an increase in activated T cells. Detailed analysis by age group revealed a striking transition in the pattern of CD4+ and CD8+ cell populations. The CD4:CD8 ratio, higher in boys than girls for ages 12-16, was reversed to the "adult" pattern in 17-19 year olds, with a higher CD4:CD8 ratio in girls. These data provide important baseline values for healthy children and stress the importance of establishing normative ranges for pediatric subjects separately from adults.

Adolescent