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Biomedical subjects

W C Cooper

Publications and source records attributed to W C Cooper.

At least 19 recordsLinked to original sources

Acquired and R-gene-mediated resistance against the potato aphid in tomato.

We examined the effects of three forms of host plant resistance in tomato, Lycopersicon esculentum, on the potato aphid, Macrosiphum euphorbiae. Mi-1.2, a resistance gene (R-gene) in tomato that deters aphid feeding, reduced the population growth of both potato aphid isolates tested, although it appeared to have a greater impact on isolate WU11 than on isolate WU12. The results suggest that there may be quantitative differences in virulence between these two aphid isolates. We also examined two distinct forms of acquired resistance in tomato, jasmonic acid (JA)-dependent and salicylic acid (SA)-dependent induced defenses. Exogenous foliar application of JA triggered expression of a JA-inducible proteinase inhibitor in tomato cultivars with and without Mi-1.2, although the effects of treatment on aphid performance differed between these cultivars. JA-treatment reduced aphid population growth on a susceptible tomato cultivar that lacks Mi-1.2, but did not significantly enhance or inhibit aphid control on a near-isogenic resistant tomato cultivar that carries this gene. Foliar application of an SA analog, benzothiadiazole (BTH), was used to induce SA-dependent defenses. BTH treatment reduced the population growth of both aphid isolates on a susceptible tomato cultivar, and also enhanced aphid control on a resistant cultivar. The results indicate that both SA- and JA-dependent acquired resistance in tomato have a direct negative effect on a phloem-feeding insect. Furthermore, this study demonstrates that acquired resistance and R-gene-mediated resistance can interact for enhanced suppression of insect herbivores.

Animals↗

Detection of fluorescently labeled actin-bound cross-bridges in actively contracting myofibrils.

Myosin subfragment 1 (S1) can be specifically modified at Lys-553 with the fluorescent probe FHS (6-[fluorescein-5(and 6)-carboxamido]hexanoic acid succinimidyl ester) (Bertrand, R., J. Derancourt, and R. Kassab. 1995. Biochemistry. 34:9500-9507), and solvent quenching of FHS-S1 with iodide has been shown to be sensitive to actin binding at low ionic strength (MacLean, Chrin, and Berger, 2000. Biophys. J. 000-000). In order to extend these results and examine the fraction of actin-bound myosin heads within the myofilament lattice during calcium activation, we have modified skeletal muscle myofibrils, mildly cross-linked with EDC (1-ethyl-3-[3-(dimethylamino)propyl]carbodiimide) to prevent shortening, with FHS. The myosin heavy chain appears to be the predominant site of labeling, and the iodide quenching patterns are consistent with those obtained for myosin S1 in solution, suggesting that Lys-553 is indeed the primary site of FHS incorporation in skeletal muscle myofibrils. The iodide quenching results from calcium-activated FHS-myofibrils indicate that during isometric contraction 29% of the myosin heads are strongly bound to actin within the myofilament lattice at low ionic strength. These results suggest that myosin can be specifically modified with FHS in more complex and physiologically relevant preparations, allowing the real time examination of cross-bridge interactions with actin in in vitro motility assays and during isometric and isotonic contractions within single muscle fibers.

Actins↗

An updated study of taconite miners and millers exposed to silica and non-asbestiform amphiboles.

This is the second update of a study of 3,444 taconite miners and millers who were first exposed to taconite, with associated exposures to silica and nonasbestiform amphiboles, in the period 1947 through 1958. Previous analyses of deaths through 1977, and again through 1983, showed no significant excess deaths from any specific causes. The present study continues the follow-up through 1988, adding 14,748 person-years of observation and 261 death certificates for analysis. The population, reduced to 3,431 because of the detection of 13 earlier duplications, has now been observed for 101,055 person-years, with 1,058 deaths and 1,039 death certificates. Death certificates were obtained for 98.2% of those known to be dead. The total number of deaths was significantly fewer than expected. Based on US rates, the standardized mortality ratio (SMR) was 83 (ie, 83% of expected). Based on Minnesota death rates, it was 91. With both US and Minnesota death rates, the SMRs for malignant neoplasms, cancer of the respiratory tract, cancer of the digestive system, heart disease, nonmalignant respiratory disease, and cirrhosis of the liver were all below 100. Slightly elevated SMRs were found for cancer of the colon, cancer of the kidney, and lymphopoietic cancer. These elevations were not statistically significant. Separate analyses were made of total deaths, lung cancer deaths, and kidney cancer deaths in men who had worked with taconite for time periods of less than 1 year, 1-5 years, 5-10 years, and over 10 years, during observation periods less than 10 years, 10-20 years, and over 20 years.(ABSTRACT TRUNCATED AT 250 WORDS)

Dust↗

Deaths from chronic renal disease in U.S. battery and lead production workers.

This report is based on an analysis of deaths in 4519 battery plant workers and 2300 lead production or smelter workers during the years 1947 to 1980. Causes were coded to the seventh (1955) revision of the International Classification of Diseases. There were significant excess deaths for "other hypertensive disease" (444-447) and "chronic nephritis" (592-594) in both cohorts, the standardized mortality ratios (SMRs) being 320 and 475, respectively, for the former causes and 222 and 265 for the latter. Proportionate mortality analysis, which adjusted for race, also showed elevated ratios, 241 and 388 for the former causes and 296 and 186 for the latter. Deaths from other hypertension-related diseases did not show comparable excesses. Renal cancer deaths were fewer than expected, SMRs being 41 and 74, respectively.

Humans↗

Mortality of workers in two Minnesota taconite mining and milling operations.

Mortality during the years 1947 to 1983 was studied in 3,444 men employed for at least 3 months in Minnesota taconite mining operations during the years 1947 to 1958. During 86,307 person-years of observation, there were 801 deaths for a standardized mortality ratio (SMR) of 88 (US white male rates) or 98 (Minnesota rates). The 41 deaths from respiratory cancer were fewer than expected, the SMR being 61 (P less than or equal to .01) (US rates) and 85 (Minnesota rates). There were 25 respiratory cancers 20 or more years after first taconite employment, for an SMR of 57 (P less than or equal to .01) (US rates). SMRs for colon cancer, kidney cancer, and lymphopoietic cancer were elevated, but below the level of statistical significance. There was one death from pleural mesothelioma, 11 years after first taconite employment, in a man with long prior employment as a locomotive operator. The pattern of deaths did not suggest asbestos-related disease in taconite miners and millers.

Asbestos↗

Study of chest radiographs and pulmonary ventilatory function in perlite workers.

A review of chest films from 152 workers who had been employed five or more years in perlite mining or processing showed none with small opacities of profusion 1/0 or higher. There were 14 films with doubtful changes (0/1), but these showed no correlation with type or duration of employment. Pulmonary function was measured in 122 current employees from the same plants. Multiple regression analysis showed no significant association between years of employment in perlite and either forced vital capacity (FVC) or forced expiratory volume (FEV1). There was a significant association between pack-years of cigarettes and both measurements. In 66 workers tested in 1975 and again in 1983, there was an average annual decrease in FVC of 32 mL, with 26 mL predicted by the Knudson formula, which is based on nonsmokers. The average annual decrease in FEV1 was 24 mL with 26 mL predicted. Comparison of groups with differing smoking patterns showed that the decreases in both FVC and FEV1 were associated with smoking. The 28 men who had added four or more pack-years in the interval between tests showed decreases in FVC and FEV1 of 44 mL/year and 31 mL/year, respectively, with 26 mL/year predicted for both groups. Those with less than four added pack-years (which included 26 nonsmokers) had decreases in FVC and FEV1 of 23 mL/year and 19 mL/year with 26 mL/year and 27 mL/year predicted.

Adult↗

Mortality among employees of lead battery plants and lead-producing plants, 1947-1980.

Two cohorts of male lead workers, 4 519 battery plant workers and 2 300 lead production workers, all of whom had been employed for at least one year during the period 1 January 1946 through 31 December 1970, were observed for mortality during the 34 years from 1 January 1947 through 31 December 1980. Vital status as of the closing date was determined for 94.7% of the former group and 91.6% of the latter. There were 1 718 deaths in the first cohort and 621 in the second. Mortality from all causes combined was significantly greater than expected in each cohort, the standardized mortality ratio (SMR) being 107 and 113, respectively. Among the battery plant workers the greater than expected mortality rate resulted in large part from a significant number of excess deaths from malignant neoplasms (SMR 113), other hypertensive disease (mainly renal) (SMR 320), chronic nephritis (SMR 222), and a group of ill-defined conditions (SMR 355). Among the lead production workers the pattern was similar, with a significant number of excess deaths from other hypertensive disease (SMR 475), hypertensive heart disease (SMR 203), chronic nephritis (SMR 265), and ill-defined conditions (SMR 214). There was also a significant excess of deaths from external causes (SMR 143). The SMR for total malignancies was 113, but this value was not significantly elevated at the 5% level. In neither cohort were deaths from cerebrovascular disease in significant excess, the SMR being 93 and 132, respectively. A proportionate mortality analysis showed that the excess deaths from cerebrovascular disease and from hypertensive heart disease among smelter workers were in part due to the high proportion of nonwhites in the smelter populations. The stomach, liver, and lungs were the sites responsible for most excess cancer deaths in both cohorts, but the elevated SMR values were statistically significant only for gastric and lung cancers in battery plant workers. There were no excess deaths from malignancies of the kidney, brain, or lymphopoietic system in either cohort. It is impossible to relate the observed mortality to levels of lead exposure; because of meager quantitative information prior to 1960. It is known that past exposures had been very high. Ethnicity, diet, alcohol, and cigarette smoking could not be ruled out as possible confounding etiologic factors for the cancer deaths.

Humans↗

A method for volume determination of the orbit and its contents by high resolution axial tomography and quantitative digital image analysis.

The various congenital and acquired conditions which alter orbital volume are reviewed. Previous investigative work to determine orbital capacity is summarized. Since these studies were confined to postmortem evaluations, the need for a technique to measure orbital volume in the living state is presented. A method for volume determination of the orbit and its contents by high-resolution axial tomography and quantitative digital image analysis is reported. This procedure has proven to be accurate (the discrepancy between direct and computed measurements ranged from 0.2% to 4%) and reproducible (greater than 98%). The application of this method to representative clinical problems is presented and discussed. The establishment of a diagnostic system versatile enough to expand the usefulness of computerized axial tomography and polytomography should add a new dimension to ophthalmic investigation and treatment.

Adult↗

The health implications of increased manganese in the environment resulting from the combustion of fuel additives: a review of the literature.

Methylcyclopentadienyl manganese tricarbonyl (MMT) is effective in raising the octane level of gasoline and is currently used in Canada for that purpose in a maximal concentration of 18 mg Mn/l (slightly less than 0.07 g Mn/U.S. gal). It has been estimated that if MMT were used in all U.S. gasoline in these amounts, the median increase of Mn in ambient air would be not more than 0.05 microgram Mn/m3, with increments generally less than 0.5 microgram Mn/m3 along urban corridors. The scientific literature was reviewed to determine how the increases in environmental manganese predicted from MMT use would relate to the amounts in the natural environment and necessary to life and to the concentrations associated with toxic effects. Even with additional manganese from the use of fuel additives, total Mn intakes would remain within the range of average amounts absorbed from food and water. Respirable manganese in ambient air due to MMT combustion would be many order of magnitude below the concentrations associated with occupational manganism and respiratory problems and also below those reported in isolated episodes of respiratory symptoms in communities near ferromanganese plants. Evidence was reviewed on the possibilities of: (1) increased absorption of inhaled manganese compared with ingested manganese; (2) hypersusceptibility of infants and persons of advanced age; and (3) increased absorption associated with iron deficiency. While relevant to high levels of exposure, these factors would not be expected to lead to toxic effects from the very low concentrations of Mn resulting from MMT use. Experimental animals that inhaled the combustion products of MMT in concentrations of approximately 10, 100, and 1000 micrograms Mn/m3 for 9 mo did not show toxic effects, although there was temporary elevation of tissue levels of Mn. Rhesus monkeys, susceptible to the neurologic effects of Mn, showed no symptoms after inhaling the combustion products of MMT in concentrations of 100 micrograms Mn/m3 for up to 66 wk. Monkeys exposed to 5000 microgram Mn/m3 also showed no symptoms. There is thus a wide margin of safety between the intakes of Mn essential to health and the high concentrations that have been associated with toxic effects. The small amounts of manganese added to the environment by the combustion of MMT used as a fuel additive would be comparable to the normal background and should not create health problems.

Aging↗

A 26-year radiographic follow-up of workers in a diatomite mine and mill.

Chest roentgenograms of 473 employees of a California diatomite plant were reviewed as part of periodic reevaluation of the efficacy of the dust control program. The plant's processing of diatomite included flux-calcination, which provided opportunities for exposure to cristobalite. The films examined were those of workers with at least five years of service. Only 11 films were interpreted as showing changes consistent with pneumoconiosis, i.e., small opacities of profusion categorized as 1/1 or greater. Only six were classified as 1/2 or more. All who developed categories 1/1 or higher during their employment had more than 25 years of service. No large opacities were reported. The low prevalence of abnormalities and the absence of definite pneumoconiosis in employees with fewer than 25 years of service was in striking contrast with findings in 1953. At that time more than 25% of those with five or more years of employment had roentgenographic evidence of pneumoconiosis and over 10% had confluent changes producing large opacities.

Adult↗

Epidemiologic study of vinyl chloride workers: mortality through December 31, 1972.

A population of 10,173 men, employed in 37 plants, was identified as having worked for at least one year in jobs involving probable exposure to vinyl chloride monomer (VCM) prior to January 1, 1973. Of the 9677 men whose vital status was determined, 707 were known to have died. For 699, death certificates were obtained. The standardized mortality ratio (SMR) for all causes was 89, that for all malignancies was 104. The only type of malignancy found in significant excess was in the category of malignant neoplasms of the brain and other parts of the nervous system; 12 deaths occurred where 5.9 were expected, for an adjusted SMR of 203. There were slight but inconclusive upward trends in all malignancies, and for malignancies of the respiratory tract, digestive tract, and central nervous system associated with reported levels of maximum exposure to VCM. When groups in whom less than 20 years had elapsed from the first exposure were compared with those with 20 or more elapsed years, and 25 or more elapsed years, no significantly different SMR's were detected for major primary sites of malignancy. Plans for an updated study of mortality, to include deaths in the period 1973-1979 are briefly discussed.

Brain Neoplasms↗

Combined surgery and cryotherapy for diffuse malignant melanoma of the conjunctiva.

Two patients who had refused exenteration for widespread conjunctival melanoma were treated by a combination of cryotherapy and surgical excisions. Cryotherapy was delivered only to the extensive areas of flat intraepithelial melanocytic proliferation (precancerous melanosis), while the surgical excisions were performed on the focal nodules, representing localized invasive melanoma. In our two patients, the invasive nodules measured, respectively, 1.2 and 1.5 mm in greatest thickness, placing them in a low to borderline risk group for metastasis. Repeated cryoapplicatons were required to control the widespread flat intraepithelial disease. The conjunctiva tolerated these procedures well because the substantia propria is not sacrificed as it must be in surgical conjunctivectomy, allowing comparatively normal reepithelialization to occur from adjacent zones, after the treated epithelium containing the melanocytes sloughs. No evidence of invasive melanoma (cancerous melanosis) has developed in any of the cryotreated areas of intraepithelial disease (precancerous melanosis); sequential biopsies have established that the atypical melanocytes have disappeared from the epithelium.

Adult↗

Flunisolide metabolism and dynamics of a metabolite.

Flunisolide (6 alpha-fluoro-11 beta,16 alpha,17 alpha,21-tetrahydroxypregna-1,4-diene-3,20-dione 16,17-acetonide) is a potent corticoid used clinically in topical formulations. Three men were given single 2-mg intravenous and oral doses of 14C-labeled flunisolide and plasma and urine concentrations of flunisolide and a major metabolite, 6 beta,11 beta,16 alpha,17 alpha,21-penta-hydroxypregna-1,4-diene-3,20-dione 16,17-acetonide (6 beta-OH metabolite) were determined. Oral flunisolide was metabolized rapidly and extensively to the 6 beta-OH metabolite and to conjugates; comparison in the intravenous dose kinetics suggested significant first-pass metabolism. In a separate study in 12 normal subjects, flunisolide in plasma was quantitated by radioimmunoassay (RIA); average systemic availability was 20%. The apparent volume of distribution (Vd beta) of flunisolide was large and systemic clearance and apparent oral clearance values were high. The 6 beta-OH metabolite had corticoid activities no more than 3 times that of hydrocortisone in rats as measured by thymolytic, anti-inflammatory, and adrenal-suppressive assays, whereas flunisolide had 180 to 550 times the activity of hydrocortisone. These data offer a metabolic explanation for the clinical observation that flunisolide can be administered intranasally and by inhalation in therapeutically effective doses without causing significant reduction in adrenal function.

Administration, Oral↗

Chrysotile asbestos in a California recreational area.

Dustfall along roads and trails being used recreationally in the Clear Creek area of San Benito County, California, located in the New Idria serpentinite, was found to be 90 percent or more chrysotile asbestos. Personal samplers worn by motorcyclists using one of the trails showed concentrations of airborne fibers ranging from 0.3 to 5.3 fibers per milliliter, according to methods prescribed for monitoring occupational exposures. The present workplace standard for brief exposures to asbestos is 10 fibers per milliliter; 5 fibers per milliliter is the proposed standard. The average total dust concentration estimated from personal samplers was approximately 20 milligrams per cubic meter of roughly 90 percent chrysotile. To our knowledge, this is the first demonstration of asbestos exposures of this magnitude, in size ranges known to be pathogenic, resulting from natural deposits not associated with mining, milling, or industrial use.

Air Pollutants↗