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Biomedical subjects

R R Cook

Publications and source records attributed to R R Cook.

70 records · Page 4Linked to original sources
PubMed1984

Kinetics of hydrolysis of peptide thioester derivatives of arginine by human and bovine thrombins.

Several peptide thioester substrates have been synthesized and tested with human thrombins (alpha, gamma, and nitrated), bovine thrombin, trypsin, and Factor X alpha beta. The substrates include various thioalkyl esters, thiobenzyl esters with substitution in the 4-position, substrates containing additional residues on the amino-terminal side of the scissile bond (P extended substrates) and one substrate containing additional residues on the carboxyl-terminal side (P' extended substrate). Neither the P nor the P' extensions resulted in significantly increased specificity; however, with one P extended substrate, D-Phe-Pro-Arg-SBzl, the KM with bovine thrombin (0.72 microM) was the second lowest KM yet reported. The results of this study underscore the importance of P vs. P' extension for thrombin substrates. The kinetic constants of the thiobenzyl esters were found to be little affected by the 4-position substitutions. A comparison of gamma-thrombin and nitrothrombin shows them to be quite similar kinetically, while both are significantly less reactive than alpha-thrombin. With these substrates, trypsin, bovine thrombin, and Factor X alpha beta have kcat/KM values in the approximate ratio of 35:10:1, respectively. The results presented here should be of value in the future design of reactive yet specific substrates for thrombin. The comparisons between the various enzymes could be helpful in clarifying the nature of their active sites.

Animals↗
PubMed1983

Benzyl p-guanidinothiobenzoate hydrochloride, a new active-site titrant for trypsin and trypsin-like enzymes.

Benzyl p-guanidinothiobenzoate hydrochloride was synthesized and demonstrated to be useful for active-site titration of bovine trypsin, bovine thrombin, human lung tryptase, bovine activated protein C, human Factor XIIa fragment and bovine Factor Xa beta. The titration is based on rapid formation of a stable acyl-enzyme with a stoichiometric release of benzyl thiol. Thiol production is measured quantitatively by including 4,4'-dithiodipyridine in the reaction mixture and measuring the increase in absorbance at 324 nm. Ellman's reagent has also been successfully employed, allowing measurement at 410 nm. Unlike p-nitrophenyl p'-guanidinobenzoate, the thioester titrant reacts slowly with chymotrypsin A alpha thus eliminating interference by this enzyme in most titrations. Advantages of this reagent as a titrant include: flexibility in detection of the released thiol, selectivity between trypsin and chymotrypsin-like enzymes, minimal pH-dependence of the epsilon of the absorbing species, relative stability of the reagent under titration conditions, and high epsilon at pH 7.2 with either 4,4'-dithiodipyridine or Ellman's reagent. The reagent should prove useful as an alternative to p-nitrophenyl p'-guanidinobenzoate hydrochloride for the determination of active-site concentrations of the enzymes employed, as well as of other related enzymes.

Animals↗
PubMed1983

Medical and morbidity surveillance findings among employees potentially exposed to TCDD.

Available medical and morbidity surveillance findings from 1976 to 1978 for two employee cohorts potentially exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) were compared with those of matched unexposed employees. The medical surveillance findings were derived from a screening programme offered to all active employees and included an analysis of various medical history questions and blood chemistry results. Group medical insurance claims served as the source of morbidity surveillance data and the period prevalence of selected diseases was analysed. Few significant differences between the exposed and unexposed were detected. Among the cohort of employees potentially exposed during the manufacture of 2,4,5-trichlorophenoxyacetic acid (2,4,5,-T), a significantly greater frequency of x-ray proved ulcer was reported and significantly more members of this group had diseases of the digestive system diagnosed. Such findings were absent in the more highly TCDD-exposed cohort engaged in 2,4,5-trichlorophenol production, making it unlikely that dioxin was a cause.

2,4,5-Trichlorophenoxyacetic Acid↗
PubMed1983

A case-control study of brain tumor mortality at a Texas Chemical plant.

A plant-based case-control study was undertaken to investigate a possible excess of brain tumor mortality identified at a Texas Chemical plant from a sample-based cohort study. Work histories and presumptive exposures of 28 former employees who had died of primary intracranial neoplasms were contrasted with those of two matched comparison groups in an effort to identify a possible etiologic agent. Because the sample-based cohort study suggested they might be at increased risk, those employees hired prior to 1945, those employed from one to four years and those employed for 20 or more years were studied separately. No statistically significant associations were found, although an elevated risk was suggested for employment in the machine shop prior to 1945 based on three exposed cases.

Adult↗
PubMed1983

An investigation of brain tumors among chemical plant employees using a sample-based cohort method.

Using a modification of the traditional cohort mortality methodology, risk estimates of death due to brain tumors were calculated for production and nonproduction employees of Dow Chemical U.S.A., Texas Division. A total of 25 malignant, benign and unspecified brain tumors were identified using a geographically limited record-linkage process. Expected deaths were extrapolated from 1,666 white males in a 5% sample of the 1940 through 1977 total workforce. The resulting sample-based standardized mortality ratios (which were not evaluated for statistical significance) suggest, at most, only a slight increased risk of mortality from brain tumors for the overall time period. There was, however, a probable elevated risk associated with first employment prior to 1945. To date, diminished risk has been noted for those hired during subsequent years.

Adult↗
PubMed1982

Survey of reproductive events of wives of employees exposed to chlorinated dioxins.

To determine whether paternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) or other polychlorinated dioxins might be associated with adverse pregnancy outcomes, an interviewer-administered questionnaire survey was conducted among wives of Dow Michigan Division employees in the Midland, Michigan, area who had been potentially exposed to dioxins. A control group consisted of wives of employees who had no dioxins exposure and whose hire dates were comparable to those of the men in the exposed group. A total of 737 conceptions, which resulted in 637 live births and 10 stillbirths and spontaneous abortions, were identified as having paternal exposure; 2031 conceptions, resulting in 1785 live births and 246 stillbirths and spontaneous abortions, were identified as having no paternal exposure to any isomer of dioxin. Odds ratios were calculated for dependent variables consisting of spontaneous abortions, stillbirths, infant deaths and several categories of congenital malformations. Trend analysis was performed for duration-of-paternal-exposure of 12 months or less, or more than 12 months. Overall, no statistically significant associations were found between any exposure and pregnancy outcome, either before or after stratification by pertinent sets of up to nine covariables.

Abnormalities, Drug-Induced↗
PubMed1982

Case-control study of brain tumor deaths among employees at a chemical manufacturing plant.

Recent studies have reported an increased risk of death from primary intracranial neoplasms among employees in the petrochemical industry. One of them, a NIOSH/OSHA county-based case-control study, suggested a twofold risk for having ever been employed at the Texas Division of Dow Chemical U.S.A. Using the case-control approach, we compared 24 brain tumor cases among employees at this large, diverse chemical plant in Texas with two sets of age-, race-, and sex-matched controls to determine if a risk could be associated with job assignment in a particular process area, with presumptive exposure to a major process chemical, or with a number of other occupationally related and unrelated variables. Results implicated no specific area or chemical. The only significant findings were an elevated odds for being hired prior to 1950 and a negative correlation with employment greater than 10 years. Further, preliminary calculations of expected deaths from primary intracranial neoplasms among the employee cohort suggested there was no excessive risk.

Adult↗
PubMed1980

Mortality experience of employees exposed to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

This study describes the mortality experience of a cohort of 61 males involved in a 1964 chloracne incident. Presumably as a result of skin absorption of the process contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin), 49 of these trichlorophenol production workers developed the skin condition. Within the limitations posed by cohort size and length of follow-up, TCDD does not appear to have adversely affected mortality experience. Overall, four deaths occurred and 7.8 were expected. Of these, one death was due to cardiovascular disease (3.8 expected) and three deaths were attributed to cancer (1.6 expected). None of the findings were statistically significant at alpha = 0.05. Further follow-up is contemplated.

Acne Vulgaris↗
PubMedDate not supplied

A cross-sectional study of ethylene glycol monomethyl ether process employees.

Human exposures to ethylene glycol monomethyl ether have been associated with hematological and neurological abnormalities. Recent animal toxicology studies have also reported testicular atrophy. To determine whether employees potentially exposed to ethylene glycol monomethyl ether during manufacturing and packaging had a higher prevalence of anemia, leukopenia, or sterility than an in-plant comparison group, a cross-sectional study was conducted at the Michigan Division of Dow Chemical U.S.A. Blood samples on 65 of 97 potentially exposed and control white males, and semen samples from a subset of 15 were analyzed. With the possible exception of smaller testicular size, no gross abnormalities or clinically meaningful differences in hematological or fertility indices were noted. Results of regression modeling suggested that white blood cells and hemoglobin might be decreased at higher exposure levels.

Adult↗
PubMedDate not supplied

Mortality experience of employees with occupational exposure to DBCP.

Concern about the carcinogenic potential of 1,2-dibromo-3-chloropropane(DBCP) has arisen recently, focusing on six organ sites: stomach, liver, kidney, lung, testes, and skin. To examine the mortality experience of persons potentially exposed, a cohort of 550 employees involved in production and formulation from 1957 to 1976 was defined. A total of 35 deaths was observed through 1979 (39.2 expected). No statistically significant excess was observed for any cause of death. No cancer deaths were noted for five of the hypothesized sites. For the lung cancer category, five deaths were observed (2.7 expected, P greater than .135), two of which occurred in a subgroup directly exposed for at least 1 yr (0.5 expected, P greater than .077). Aside from arsenicals exposure, potential confounding resulting from smoking or multiple chemical exposures could not be evaluated.

Antinematodal Agents↗