Search PubMed⌕ Search

Biomedical subjects

K C Chu

Publications and source records attributed to K C Chu.

At least 73 records · Page 4Linked to original sources
PubMed1983

A new method for the analysis of cohort studies: implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure.

Implications of the multistage theory of carcinogenesis for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different patterns of excess risk related to duration of exposure, age at initial exposure, and follow-up time since exposure stopped, depending upon which stage of the carcinogenic process is affected by the carcinogen, i.e., action at an early stage or a late stage. New statistical methodologies are proposed to examine these patterns and are applied to the lung cancer mortality experience from a cohort study of smelter workers exposed to arsenic. Under this multistage hypothesis, the results indicate that arsenic exerts a definite late stage effect though an additional effect at the initial stage cannot be ruled out. The possibilities of biased conclusions resulting from incomplete exposure histories and lack of smoking information are also discussed as well as implications of these results to experimental animal studies.

Arsenic↗
PubMed1983

Coxsackievirus B4 hepatitis in monkeys.

Hepatitis was produced by Coxsackievirus B4, an agent highly infectious to man, in 3 of 9 experimentally infected squirrel monkeys. Although the virus could not be isolated from the livers of these monkeys, viral antigen was found in the liver cells of one monkey with severe hepatitis by direct immunofluorescent antibody staining, and a virus crystal was found in the kidney of this monkey by electron microscopy. These and previous studies strongly suggest that the Coxsackievirus can exist in the liver and other tissues in a dormant or slow viral state.

Animals↗
PubMed1983

Implications of the multistage theory of carcinogenesis applied to occupational arsenic exposure.

The multistage theory of carcinogenesis and its implications for evaluating the effect of exposure to carcinogens in the workplace are described. This theory predicts different relationships between excess carcinogenic risk and duration of exposure, age at initial exposure, and follow-up time since exposure stopped. These relationships are shown to depend on the stage of the carcinogenic process affected by the carcinogen, i.e., action at an early stage or a later stage. The patterns of excess lung cancer mortality were examined for a cohort of copper smelter workers exposed to atmospheric arsenic and other contaminants. Under this multistage hypothesis, the results indicate that arsenic appears to exert a definite effect on a late stage of the carcinogenic process, although an additional effect at the initial stage cannot be conclusively ruled out. Other factors, such as exposure to sulfur dioxide in the environment, calendar year at start of employment, and the potential bias resulting from incomplete exposure histories are also discussed as well as the implications of these results to experimental animal studies.

Adult↗
PubMed1982

Coxsackievirus B4 nephritis in the squirrel monkey.

Seventeen squirrel monkeys (Saimiri sciureus) were experimentally infected with Coxsackievirus B4, and the kidneys, as well as other organs, were studied for pathological changes induced by the virus. Seven (41%) of these monkeys developed renal lesions--interstitial and glomerular. The Coxsackievirus was identified in 4 of these 7 monkeys (by isolation from the renal tissue in 2, by immunofluorescence staining of viral antigen in 1, and by electron microscopic finding of viral particles in 1). The renal lesions produced by Coxsackieviral infection described in this report resemble those seen in renal disease in man. These findings support the concept that viruses can produce glomerular and interstitial renal disease. This report also describes a good animal model for the study of viral disease of the kidney.

Animals↗
PubMed1982

Experimental viral arthritis.

An early, acute arthritis was observed in 8 of 22 mice experimentally infected with respiratory syncytial virus. No abnormalities were found in the joints of the 12 control mice. The pathological changes in joints of the infected animals included pannus formation and erosion, resembling changes that occur in arthritis in man, including rheumatoid arthritis. It is proposed, therefore, that viruses may play an aetiological role in acute and chronic arthritis in man. These investigations provide a model for studying pathology of arthritis in mice produced by a virus which also infects man.

Animals↗
PubMed1981

Evaluating statistical analyses and reproducibility of microbial mutagenicity assays.

The NCI/NTP has completed the first phase of a 4-laboratory study on the reproducibility of testing chemicals for mutagenicity in the Salmonella/microsome assay. This paper is a report of the statistical analysis of some of that data. This analysis involved (1) identifying and removing spurious data; (2) determining the adequacy of the remaining data in making a decision on the mutagenicity of the test chemical; (3) performing the statistical tests; and (4) interpreting the results. Using this procedure, 7 approaches were used to determine the mutagenicity of a test. These approaches were the (1) 2-fold rule, (20 modified 2-fold rule, (3) one-way analysis of variance (homogeneity test), (4) test for linear trend, (5) combination of 3 and 4, (6) 97.5th percentile threshold rule and (7) confidence interval threshold rule. The conclusions drawn by each rule were compared to the microbiologists' interpretation, and the results of these comparisons were presented. In addition, the strengths and weakness of each rule were discussed. The reproducibility of the assay in this study was examined, and a discussion of the significance of these results was presented.

Histidine↗
PubMed1981

Variability in the rates of some common naturally occurring tumors in Fischer 344 rats and (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice.

Variability inthe incidence rates of some common naturally occurring tumors for 72 inbred F344 rat and 54 (C57BL/6N x C3H/HeN)F1 (B6C3F1) mouse control groups used in carcinogenesis bioassays was evaluated. Significant heterogeneity of control rates was observed in at least two of six laboratories for lymphomas-leukemias, liver tumors, and pituitary tumors in the male rat and for pituitary tumors and endometrial stromal polyps in the female rat. Significant interlaboratory heterogeneity was observed for several tumor types in the F344 rat. In contrast, control incidence rates for tumors of the lung and liver and lymphomas-leukemias in B6C3F1 mice were relatively homogeneous within four of five laboratories. Significant interlaboratory heterogeneity was observed, however, for these mouse tumors. The causes of significant heterogeneity in naturally occurring tumor incidence rates within and among laboratories are unknown. Although the most appropriate and important comparison of an experimental group is with its matched control, there may be instances in which the historical control rates provide relevant data needed to clearly interpret carcinogenesis bioassay results. With the use of data from bioassays of 4-chloro-m-phenylenediamine and nitrilotriacetic acid, two examples are presented to demonstrate the usefulness of the historical control data.

Adrenal Gland Neoplasms↗
PubMed1981

Review of experimental carcinogenesis by compounds related to vinyl chloride.

The experimental carcinogenesis results in six compounds related to vinyl chloride are reported. Vinylidene chloride, given by inhalation, was carcinogenic in male CD-1 mice, male CD rats, Sprague-Dawley rats and male Swiss mice. Trichloroethylene, given by gavage and inhalation, was carcinogenic in the B6C3F1 mice. When given by gavage, perchloroethylene was carcinogenic in the B6C3F1 mice, and dichloroethane was carcinogenic in Osborne-Mendel rats and B6C3F1 mice. Dibromoethane, given by gavage and inhalation, was carcinogenic in B6C3F1 mice, F344 rats and Osborne-Mendel rats. Finally, epichlorohydrin was carcinogenic in male Sprague-Dawley rats and B6C3F1 mice.

Aerosols↗
PubMed1979

Neoplastic and nonneoplastic lesions in aging (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice.

Neoplastic and nonneoplastic lesions in untreated (C57BL/6N x C3H/HeN)F1 (B6C3F1) mice used as controls in carcinogenesis tests were tabulated and evaluated. The most common neoplasms in 2,543 male mice were hepatocellular adenomas and carcinomas. In 2,522 female mice, common tumors were lymphomas, leukemias, pulmonary adenomas and carcinomas, hepatocellular adenomas and carcinomas, and pituitary adenomas. The risk of developing most neoplasms increased with the age of the mouse. Hepatocellular carcinomas metastasized in 12% of the animals with these tumors. Other than lymphomas and leukemias, few other tumors metastasized. Nonneoplastic lesions included cystic hyperplasia of the uterus, nephritis, ovarian and uterine cysts, inflammatory lesions of the lung, mineralization in the brain, and focal hyperplasias in several tissues. The focal hyperplasias in lung and pituitary, adrenal, and thyroid glands were suggestive of the early stages of neoplasia. Comparative aspects of lesions in aging mice and their interpretation in carcinogenesis tests are discussed.

Age Factors↗
PubMed1979

Statistical issues in interpretation of chronic bioassay tests for carcinogenicity.

The interpretation of chronic bioassay tests for carcinogenicity requires that the data be appropriately recorded. A "case history" for each animal links the pathology data for each organ of each animal to the length of its life. This information can be used in interpretation of the tumor incidences in light of the survival information. The role of historical controls was discussed, and the use of significance tests in a multidisciplinary approach to the assessment of the pattern of tumor response was suggested. Multiple comparison methods valid for the interpretation of continuous (or measurement) data do not apply to the discrete data analyses used in these studies. The ideas and methods of these studies were applied to an animal study of chloroform.

Animals↗
PubMed1977

False-positive and false-negative rates for carcinogenicity screens.

The implementation of a number of chemical carcinogen screening programs has been accompanied by the observation that some screens might have high false-positive error rates. With designs presently used at the National Cancer Institute and historical spontaneous tumor rates based upon control animals in previous experiments, we compute upper bounds on the false-positive error rates for several screening strategies. False-positive results are much less likely to occur at tissue sites with low spontaneous tumor rates; hence the site at which a significant tumor increase occurs is important. There is danger in relying solely upon the finding of statistical significance without incorporating biological knowledge and corroborative evidence such as the presence of a dose-response relationship or experimentally consistent results in different species or sexes. A report by the National Cancer Institute Carcinogenesis Program demonstrates these concepts.

Animals↗