The relationship of strain, sex, and body weight to survival following sublethal whole-body x-irradiation.
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Biomedical subjects
Publications and source records attributed to T J Mitchell.
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The frequency of ethyl methanesulfonate (EMS)-induced mutations to 6-thioguanine resistance in a Chinese hamster ovary cells clone K1-BH4 was studied at many EMS doses including the minimally lethal range (0-100 microng/ml) as well as the exponential killing portion (100-800 microng/ml) of the survival curve. The mutation frequency increases approximately in proportion with increasing EMS concentration at a fixed treatment time. The pooled data for the observed mutation frequency, f(X), as a function of EMS dose X, is adequately described by a linear function f(X)=10(-6)(8.73+3.45 X), where 0 less than or equal to X less than or equal to 800 microng/ml. One interpretation of the linear dose-response is that, as a result of EMS treatment, ethylation of cellular constituents occurs, which is directly responsible for the mutation. Biochemical analyses demonstrate that most of the randomly isolated 6-thioguanine-resistant variants possess a highly reduced or undetectable level of HGPRT activity suggesting that the EMS-induced mutations to 6-thioguanine resistance affect primarily, if not exclusively, the HGPRT locus.
Exposure of Chinese hamster ovary (CHO) cells clone K1BH4 to ultraviolet (UV) light at doses up to 86 ergs/mm2 did not significantly reduce cell survival, but UV doses of 86-648 ergs/mm2 produced an exponential cell killing. Observed mutation frequency ro 6-thioguannine resistance induced by UV increases approximately in proportion to increasing doses up to 260 ergs/mm2 in a range of 5-648 ergs/mm2 examined. The pooled data of mutation frequency f(X) as a function of dose X from 0-260 ergs/mm2 is adequately described by f(X)=10(-6) (13.6 + 2.04 X). That the UV-induced mutations to 6-thioguanine resistance affects the hypoxanthine-guanine phosphoribosyl transferase (HGPRT) locus is supported by the observation that all randomly isolated drug-resistant colonies contained highly reduced or undetectable HGPRT activity.
The carcinogenic and cocarcinogenic activity of synthetic smog, ferric oxide (Fe2O3) dust, and a mixture of the two air contaminants was determined in a long-term inhalation study with Syrian hamsters. Inhaled Fe2O3 particles definitely enhanced diethylnitrosamine tumorigenicity in the peripheral lung. Synthetic smog did not. When tested at a concentration of 40 ppm methane equivalents or 40 mg/m3, respectively, neither air pollutant by itself appeared carcinogenic. Fe2O3 caused pulmonary fibrosis and synthetic smog caused alveolar bronchiolization in many of the exposed animals.
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This paper presents a computer program for analyzing disease prevalence data from animal survival experiments in which there may also be some serial sacrifice. The method has been described in Biometrics 35 (1979) 221-234. The user is interrogated about the details of particular models he wishes to fit. Then a generalized EM algorithm is used to compute maximum likelihood estimates of various quantities of interest concerning the effects of treatment, time and presence of other diseases on the prevalences and lethalities of specific diseases of interest.
Streptococcus pneumoniae is a major pathogen of man causing diseases such as pneumonia, meningitis and otitis media. The mechanisms by which this organism causes these diseases are still largely unknown. The use of molecular approaches to identifying and studying putative virulence factors in combination with the application of animal models has allowed some of the mechanisms of the disease process to be defined.
Three years of field data, classical linear reservoir theory, and a new dissolution model confirm the hypothesis that residual chloride from highway deicing applications dissolves into precipitation throughout the year. The measured input includes 52 storm hyetographs and logs of salt and premix applications on an access road with a closed drainage system subject to runoff, interflow, and baseflow. The output data feature discharge and conductivity in an outlet weir measured continuously from February 1998 to May 2000. Individual storm hydrographs and pollutographs yield calibrated first flush dissolved chloride concentrations and residual solid chloride loads that persist at appreciable levels over the entire period of record. The storm calibrations imply a source strength w of 2.01 x 10(-6) s(-1) that accurately models chloride dissolution kinetics through three salt seasons on the access road. This w rests on physically plausible values for the depression storage depth zeta (3 mm) and porosity n (0.40) that store the residual chloride.
To relate the immunochemical specificity of three murine monoclonal antibodies directed against the octapeptide hormone angiotensin II (AII) to their primary structure, we have sequenced mRNA for the variable regions of their heavy and light chains. Comparison of the sequences indicates that each of the antibodies utilize very closely related V genes in both heavy and light chains. Two of these antibodies, ICH2 and ICA10, display an epitope preference for the carboxy terminus of AII. A third monoclonal antibody, KAA8, displays a lesser specificity for the carboxy terminus of AII than either ICH2 or ICA10. This antibody differs in sequence from the others mainly in the light chain complementarity determining regions (CDR) 1 and 3 and in CDR 3 (D region) on the heavy chain. We interpret these sequence differences as the basis for the observed specificity preferences.
This paper discusses some of the statistical and biological problems that are likely to be encountered when an indirect or ecological approach is used to assess the possible public health impact of general population exposures to environmental agents. For purposes of illustration, the potential association between various site-specific cancer mortality rates and chloroform levels in public drinking water supplies was considered. The analyses that were performed demonstrated that, for the data sets under consideration, there were some definite associations between chloroform levels and cancer mortality for specific sites such as the rectum-intestine and bladder. However, the marked extent to which these results were dependent on (1) the weighting scheme adopted in the analysis, (2) the presumed appropriateness of the data, and (3) the characteristics of the statistical model was also clearly illustrated. Because of these dependencies the quantitative, causal interpretation of results generated from an indirect study would appear to be a very tenuous and questionable practice in most instances.
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