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Biomedical subjects

T D Clark

Publications and source records attributed to T D Clark.

At least 37 records · Page 2Linked to original sources
PubMed1991

Effect of dietary calcium on colon carcinogenesis induced by a single injection of 1,2-dimethylhydrazine in rats.

The purpose of this study was to determine if high levels of dietary calcium could inhibit the induction of colon tumors in rats injected with a single dose of 1,2-dimethylhydrazine (DMH). Rats were given a single subcutaneous injection of DMH (200 mg/kg body weight) 2 wk before they were fed purified diets containing 5% fat and four different levels of calcium (as calcium gluconate). After 8 mo, the following incidences of colon tumors (total) were seen: 0.2% Ca, 56%; 0.5% Ca [National Academy of Sciences/National Research Council (NAS/NRC) recommended level], 75%; 1.0% Ca, 61%; 2.0% Ca, 41%. Thus, rats fed calcium at levels above or below the NAS/NRC recommendation had lower tumor incidences. The total tumor incidence and the incidence of adenocarcinomas (with or without invasion) were not significantly affected by calcium, but the incidences of benign adenomatous polyps and of distal colon tumors were significantly affected. Autoradiographic examination of [3H]thymidine-treated rats revealed that the level of calcium did not significantly alter the cell kinetic indices in the distal colon. In the proximal colon, however, the 0.2% Ca group had a significantly larger proliferative zone, with significantly more labeled cells present at the bottom of the colon crypt. Mineral analysis of tibias and serum samples revealed that rats fed higher levels of calcium had lower bone Fe and serum Mg contents, but no significant trends were seen for Ca, P, Zn or Cu. Therefore, increasing or decreasing the calcium content above or below the NAS/NRC recommendation (supplemented to low fat diets) during the promotional phase of colon carcinogenesis altered the tumor incidence, but the effect was confined to the distal colon and to benign adenomatous polyps.

1,2-Dimethylhydrazine↗
PubMed1990

Effect of dietary vitamin E on the development of altered hepatic foci and hepatic tumors induced by the peroxisome proliferator ciprofibrate.

The purpose of this study was to determine the effect of the dietary antioxidant vitamin E on hepatocarcinogenesis by peroxisome proliferators which, it is hypothesized, induce tumors by increased production of hydrogen peroxide or other oxygen radicals. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (10, 50, or 500 ppm) of alpha-tocopheryl acetate for 6 months or 21 months. The incidence of hepatic tumors and the number and volume of gamma-glutamyl-transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci were quantified. No tumors or altered hepatic foci were seen at 6 months, but at 21 months the incidence of hepatic tumors and the number and volume of altered hepatic foci were increased in rats fed higher levels of vitamin E. Indices of oxidative damage--concentrations of malonaldehyde, conjugated dienes, and lipid-soluble fluorescence products--were not affected or were lower in rats fed higher amounts of vitamin E; the enhancing effect of vitamin E on the development of altered hepatic foci and hepatic tumors, therefore, was not related to the induction of cellular oxidative damage. Hepatic peroxisomal fatty acid beta-oxidation and vitamin C concentrations were not affected by vitamin E, whereas the glutathione concentration was decreased in rats fed higher amounts of vitamin E. This study shows that increasing the vitamin E content of the diet enhances ciprofibrate-induced hepatocarcinogenesis, but the mechanism of this effect is unclear.

Adenosine Triphosphatases↗
PubMed1990

Effect of dietary selenium on the induction of altered hepatic foci and hepatic tumors by the peroxisome proliferator ciprofibrate.

The purpose of this study was to determine if the dietary antioxidant selenium could inhibit hepatocarcinogenesis induced by peroxisome proliferators, which are hypothesized to induce tumors by increased production of hydrogen peroxide or other reactive oxygen species. Rats were fed diets containing the peroxisome proliferator ciprofibrate and one of three concentrations (0.04, 0.2, or 1.0 ppm) of selenium for 6 or 21 months. The incidence of hepatic tumors and the number and volume of gamma-glutamyl transpeptidase-positive, ATPase-negative, glucose-6-phosphatase-negative, and glucose-6-phosphatase-positive foci at 21 months were lower in rats fed higher levels of selenium (no foci or tumors were seen at 6 mo). Indices of oxidative damage in the liver (thiobarbituric acid reactants, conjugated dienes, and lipid-soluble fluorescence products), however, were not decreased in rats fed the high-selenium diet. Therefore, selenium was protective against ciprofibrate-induced hepatocarcinogenesis, but not by reducing the degree of oxidative damage. The liver selenium and glutathione concentrations, and liver selenium-dependent glutathione peroxidase activity, increased as dietary selenium increased. Therefore, inhibition of carcinogenesis by selenium was correlated with increased levels of glutathione and glutathione peroxidase, but these did not inhibit the indices of oxidative damage. Peroxisomal beta-oxidation also increased with the dietary selenium content; it therefore does not appear to be a factor in the inhibition of hepatocarcinogenesis in rats fed higher levels of selenium.

Analysis of Variance↗
PubMed1989

Lack of initiating activity of the peroxisome proliferator ciprofibrate in two-stage hepatocarcinogenesis.

The peroxisome proliferator ciprofibrate was examined for its ability to initiate hepatocarcinogenesis in rats. Ciprofibrate was fed in the diet at levels of 0%, 0.01% and 0.025% for 2 weeks in order to induce steady-state peroxisome proliferation. Rats were then subjected to partial hepatectomy and then maintained for 6 months on a basal diet or one containing 0.05% phenobarbital. Ciprofibrate treatment did not increase the number or volume of altered hepatic foci (putative preneoplastic lesions). However, ciprofibrate treatment increased liver weights in a dose-dependent manner in rats which did not receive phenobarbital. It is concluded that ciprofibrate-induced peroxisome proliferation is not sufficient to induce initiation, but that a permanent change is produced which results in an increased liver weight.

Animals↗
PubMed1987

Nuclear roundness factor: a quantitative approach to grading in prostatic carcinoma, reliability of needle biopsy tissue, and the effect of tumor stage on usefulness.

Morphometric analysis and histologic grading were performed on case material from 26 patients. Relative nuclear roundness factor (RNRF) was calculated and correlated with clinical course in 14 patients undergoing prostatectomy for stage A or B prostatic carcinoma. The only patients with progression of disease were two with RNRF of 1.10. RNRF in cases without progression ranged from 0.98 to 1.07. Histologic grading by the methods of Gleason or the M.D. Anderson system failed to discriminate between the progressing and nonprogressing groups. However, when RNRF was measured in tumors initially diagnosed as stage C or D, four of eight were below 1.10, within the range of the nonprogressing low-stage cases. Thus, the usefulness of morphometry and RNRF may be limited to low-stage disease. It was additionally found that RNRF could not be reliably measured in needle biopsy specimens.

Biopsy, Needle↗
PubMed1987

Androgen receptors detected by autoradiography in prostatic carcinoma and benign prostatic hyperplastic tissue.

Androgen receptor (AR) content in prostatic tissues from patients with either cancer or benign prostatic hyperplasia (BPH) is of interest from at least two standpoints: receptors may be a feature of the pathogenesis of these conditions, and they may be important to the management and prognosis of prostatic cancer patients. For these reasons, a quantitative autoradiographic assay for AR content in prostatic tissues has been developed. Application of autoradiography to rodent tissues yielded results that were highly correlated with those from biochemical assays. Thus, the autoradiographic analyses with human tissues reported in this paper were undertaken. Average AR content in 22 prostatic carcinomas was lower than that in tissues from 14 patients with BPH; the median values of the affinity index, the quantitative estimate of receptor content, were 7.0 and 12.0, respectively. For the cancer tissues, a trend of declining receptor content with advancing stage of disease appeared but was not statistically significant. No association between receptor content and degree of tumor aggressiveness as measured by Gleason score and MD Anderson score was evident. Patient age and race were not related to receptor content in either type of tissue.

Aged↗
PubMed1987

Serum hormone levels among patients with prostatic carcinoma or benign prostatic hyperplasia and clinic controls.

This study sought to identify differences in serum hormone levels between prostatic cancer (CaP) patients, benign prostatic hyperplasia (BPH) patients, and clinic controls (CC). Serum testosterone, estradiol, and prolactin values were obtained from 35 CaP, 42 BPH, and 161 CC patients attending a single medical center between January 1984 and April 1985. Relative risk estimates adjusted for age and race were calculated to compare hormone values between each case group and the CC. The distributions of hormone values and the testosterone to estradiol (T/E) ratios were grouped into thirds with the lowest third forming the reference category. The relative risk estimates for BPH in the middle and high thirds of testosterone were greater than unity (1.26 and 2.10, respectively), whereas the relative risk estimates in the middle and high thirds of estradiol were less than unity (0.63 and 0.35, respectively). For the middle and high thirds of the T/E ratio, the relative risk estimates for BPH showed statistically significant three- to fourfold increases. Modest depression of serum testosterone and estradiol was noted for CaP patients compared to CC, although the differences were not statistically significant. This depression was interpreted to be a likely result of the malignant process rather than a cause of it, whereas the development of clinically evident BPH was felt to be a biologically plausible response to an elevated T/E ratio.

Age Factors↗
PubMed1983

Immunohistochemical demonstration of blood group antigens in neoplastic and normal human urothelium: a comparison with standard red cell adherence.

The specific red cell adherence test as a method to detect blood group antigen deletion in urothelial malignancy has been reported to yield approximately 40 per cent false negative results in 0 blood group patients. Our study of multiple sections of 8 normal ureters from blood group 0 patients and more than 220 specimens of transitional cell cancer taken from 48 patients reveals that the immunoperoxidase technique is more specific than the specific red cell adherence method in predicting subsequent invasion in blood group O(H) patients presenting with superficial transitional cell carcinomas (71 compared to 29 per cent) but is no more specific for tumors containing A or B antigens. However, immunoperoxidase staining does improve discernment of underlying histologic detail and, thereby, facilitates recognition of false positive antigen testing associated with squamous and adenomatous metaplasia. Areas of squamous and adenomatous metaplasia in specimens we tested were frequently antigen positive in invasive tumors. Therefore, we believe that these areas must be disregarded in determining antigen deletion in transitional cell carcinomas.

ABO Blood-Group System↗
PubMed1983

A comparison of clinical course with blood group antigen testing by specific red cell adherence and immunoperoxidase in ureteral and renal pelvic tumors.

Specimens of transitional cell carcinoma of the ureter and renal pelvis from 20 patients were tested for blood group antigenicity using immunoperoxidase and specific red cell adherence methods. The results of antigen testing were correlated with tumor stage and grade as well as the subsequent clinical course of the patients. The specific red cell adherence test was negative in 80 per cent and the immunoperoxidase test was negative in 40 per cent of all tumors. Of the 4 patients with positive specific red cell adherence tests 3 had high grade (II to III), invasive tumors as did 7 of 12 with tumors that were positive by immunoperoxidase testing. Blood group antigen testing did not prove helpful in predicting the clinical course of our patients. In addition, a careful review of previously published data does not support the conclusion that blood group antigen testing is a valuable predictor of upper tract tumor aggressiveness.

Adult↗
PubMed1977

Effects of streptovaricins and their degradation products on RNA-directed DNA polymerase of Rauscher leukemia virus.

The activities of streptovaricin complexes, streptovaricins, streptovals, and streptovarinic degradation products were elevated against RNA-directed DNA polymerases of Rauscher leukemia virus, DNA-dependent DNA polymerase of bacterial and mammalian cells, and DNA-dependent RNA polymerases of mammalian origin. The activities of streptovaricins were also listed for comparison purposes. The effects of streptovaricin complexes on viral DNA polymerases varied significantly from lot to lot, and streptovaricin complex lot 7 was the most active. All the streptovals and streptovaricin degradation products except varicinal A showed a marked improvement (twofold to tenfold) in activity against the viral enzyme over the parent streptovaricins. None of these compounds, however, displayed any significant effect on either the DNA polymerase of L1210 leukemia cells and Escherichia coli or the RNA polymerase of isolated nuclei of mouse liver. As a result of tests in these systems, some specific inhibitors of RNA-directed DNA polymerases of Rauscher leukemia virus were selected.

Chemical Phenomena↗
PubMed1977

Effects of streptovaricins and their degradation products on infectivity of Rauscher leukemia virus.

The virucidal effects of streptovaricin (Sv) A, SvC, SvD, streptoval (Sval) C, Sval Fc, and streptovarone were evaluated by incubation of the drug with Rauscher leukemia virus (RLV) at 37 degrees C for 60 minutes prior to dillution and addition to cells (in vitro assay) or before ip injection into animals (in vivo assay). The in vitro and in vivo assays were plaque formation and splenomegaly, respectively. A dose-related effect was observed with all six compounds with the in vitro assay. On an equimolar basis, the Sv degradation products, i.e., Sval C, Sval Fc, and streptovarone were most inhibitory, followed by SvD; SvA and SvC were least active. At 0.0625 mumoles, the three Sv degradation products inactivated over 90% of the RLV. Similar results were obtained through the in vivo assay. At 0.06 mumoles, streptovarone, Sval C, and SvD showed 78,62, and 29% inhibition of splenomegaly, respectively; SvA and SvC were essentially inactive. A direct relationship was observed between inhibition on RNA-directed DNA polymrase of RLV by these compounds and their virucidal effects. No drug given at the time of injection, however, showed any significant effect on virus infective processes in vitro or in vivo. The reason for the lack of therapeutic effects of these compounds is discussed.

Animals↗
PubMed1968

Preservation of influenza virus infectivity by lyophilization.

A method of lyophilizing influenza virus in allantoic fluid with retention of high-titer of egg infectivity is described. Five strains of virus were lyophilized, and all were much more stable than fluid virus preparations, retaining 2 to 3 logs of infectivity after storage at 37 C for 60 to 95 days. Statistical analysis of an accelerated storage test by extrapolation of viral degradation indicates that the lyophilized viruses are stable indefinitely at or below room temperature.

Animals↗