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Biomedical subjects

M Pollard

Publications and source records attributed to M Pollard.

At least 55 records · Page 3Linked to original sources
PubMed1984

Animal models and treatment of prostate cancer.

Model systems for prostate cancer in rats have been developed and used for investigations on tumor biology and therapy. The "Pollard tumors" provide a combination of in vitro and in vivo attributes by which investigations can be directed at local tumor development and spontaneous metastasis. The evolution and early applications of this model system are reviewed, and the therapeutic benefits of delayed release of cyclophosphamide are presented.

Adenocarcinoma↗
PubMed1984

An assessment of nutritional depletion following major colonic surgery.

This study was undertaken to determine the changes in basic nutritional indices associated with major colonic surgery accompanied by periods of semi-starvation. Changes in weight, serum albumin, nitrogen balance, and maximum exercise capacity were studied. Weight loss was 5.5 +/- 1 per cent, serum albumin decreased 0.20 +/- 0.15 gm per cent. Nitrogen loss was 5.9 +/- 0.9 gm per day and maximum exercise capacity decreased by 13.5 +/- 1.8 per cent. Nitrogen balance improved when amino acids were substituted for glucose as the maintenance regimen, but no corresponding improvement in exercise performance could be demonstrated. It is concluded that major colonic surgery associated with moderate periods of semi-starvation is associated with an average nitrogen loss of 5.9 +/- 0.9 gm per day and a 13.5 +/- 1.8 per cent loss in maximum exercise capacity or effective muscle mass.

Adult↗
PubMed1984

Effect of piroxicam on primary intestinal tumors induced in rats by N-methylnitrosourea.

Piroxicam, a non-steroidal anti-inflammatory agent, was administered in the feed to rats which had been inoculated intra-rectally with N-methylnitrosourea (MNU). When examined 5 months later, the piroxicam-treated rats had a significant reduction of intestinal tumors compared to tumor incidences and tumor numbers in rats which were fed drug-free diet. There was no evidence of toxicity associated with the consumption of piroxicam.

Animals↗
PubMed1984

Visualization of chromatin events associated with repair of ultraviolet light-induced damage by premature chromosome condensation.

The purpose of this study was to characterize a system with which to study chromatin events associated with the repair of u.v. light-induced damage. Quiescent normal human fibroblasts were irradiated with u.v. and the ensuing chromatin events were visualized by inducing premature chromosome condensation in the treated cells. Treatment with u.v. induced the following two types of chromatin changes reflected in the morphology of G1 premature condensed chromosomes (PCC): (i) a generalized elongation of the G1 PCC and (ii) regions of localized elongation or gaps. The degree of chromatin change was dose dependent and could be seen immediately after irradiation. The generalized elongation process continued to increase for 24 h after irradiation, suggesting it represented a cellular reaction to the u.v.-induced damage, rather than a direct physical distortion. The localized decondensation reaction was associated with the site of unscheduled DNA synthesis. Posttreatment incubation of cells in the presence of cytosine arabinoside and hydroxyurea resulted in an accumulation of gaps. The inhibitor novobiocin predominantly inhibited the formation of gap regions, suggesting that a topoisomerase-like reaction might be important in their formation. The presence of cycloheximide after u.v. irradiation had no effect on the chromatin changes, suggesting that no new protein synthesis is required for these chromatin processes associated with repair. These results suggest that the PCC technique is useful in elucidating chromatin changes associated with DNA repair after u.v. treatment and can be used to elucidate chromatin events associated with the repair of other DNA-damaging agents.

Cell Cycle↗
PubMed1984

Inhibition of intestinal tumorigenesis in methylazoxymethanol-treated rats by dietary restriction.

Male Sprague-Dawley rats were inoculated once with methylazoxymethanol (MAM) and groups were fed restricted diets for the following 140 days: Group A or B was fed a 12-g diet daily (25% restricted) from Day 10 or Day 63 after MAM, respectively. Group C or D was fed ad libitum only every other day from Day 8 or Day 31 after MAM, respectively. Control MAM-treated rats were fed the same diet ad libitum. When examined at Day 140, there was a significant reduction of intestinal tumors in Group A on the restricted diet from Day 10; however, among all other groups there were no significant differences in tumor incidences. Later onset of daily dietary restriction or of feeding and fasting every other day did not change the pattern of tumorigenesis from that which developed in control rats fed ad libitum.

Adenocarcinoma↗
PubMed1983

Purification and properties of a plasminogen activator from cultured rat prostate adenocarcinoma cells.

Zymographic analysis of the supernates from confluent cultures of a rat prostate adenocarcinoma cell line, PA-III, revealed the existence of two molecular forms of specific plasminogen activators, one of molecular weight of approximately 80 000 and another of approximate molecular weight of 45 000, in sodium dodecyl sulfate. The low molecular weight form has been purified 364-fold in 66% yield from the culture medium by a combination of gel filtration on Sephacryl S-200 and affinity chromatography on Sepharose 4B-benzamidine. The purified material possessed a specific activity of 192 000 urokinase CTA units mg-1. This enzyme displayed activity toward human Glu1-plasminogen, characterized by a Km of 1.7 +/- 0.2 microM and a Vmax of 0.53 +/- 0.1 pmol of plasmin min-1 unit-1. A synthetic chromogenic substrate, H-D-Ile-Pro-Arg-p-nitroanilide (S-2288), was found for the activator. The enzyme possessed a Km of 0.33 mM and a kcat of 55 s-1 for S-2288. The activator was found to be a serine protease, inhibited by diisopropyl fluorophosphate (iPr2PF). At a concentration of 1 mM iPr2PF, and 30 nM enzyme, the half-time of this inhibition was 3.8 min. The 45 000 molecular weight enzyme was found to be inhibited by rabbit antibodies to human urokinase, thus characterizing the activator as a member of the urokinase class. The 80 000 molecular weight enzyme was not neutralized by anti-human urokinase but was neutralized by rabbit anti-human melanoma activator, likely allowing it to be classified as the tissue activator type.

Adenocarcinoma↗
PubMed1983

The temporary postnatal decline in glucuronidation of certain phenols by rat liver.

A temporary but marked postnatal decline in UDP-glucuronosyltransferase activity occurs in homogenates and microsomes from rat liver. The profile of this trough and its time of occurrence (maximal over 13-16 days) are almost identical with the two substrates 2-aminophenol and 1-naphthol, whose rates of glucuronidation differ 10-fold. The trough is greatest with digitonin-activated preparations, least with fresh latent ('native') enzyme and intermediate when the native enzyme is treated with its specific activator UDP-N-acetylglucosamine (UDP-GlcNAc). Less detailed evidence supports similar conclusions with 4-nitrophenol as substrate. The trough is not due to the presence of an inhibitor of the transferase in rat liver at 15 days of age. Over the whole perinatal period, including the time of the trough, the enzyme in homogenates can be activated by UDP-GlcNAc; the microsomal enzyme is activated to a rather lesser degree perinatally, and evidence suggests this may be due to artefacts introduced during tissue fractionation. When the overall process of glucuronidation is studied in snips of intact liver offered high concentrations of the two different phenols, the trough is again evident over the same period as observed with broken cells, and of equal depth for both substrates. The infant rat is therefore probably less able to glucuronidate hepatically these phenols over the suckling or early weaning period than are the adult, late foetus or newborn, and may be especially incompetent at 13-16 days of age.

Aminophenols↗
PubMed1983

The suppressive effect of piroxicam on autochthonous intestinal tumors in the rat.

Male Lobund strain Sprague--Dawley (SD) rats respond to single doses of methylazoxymethanol acetate (MAM) with high incidence of intestinal tumors within 5 months. Some non-steroidal anti-inflammatory drugs (NSAIDs) can block the synthesis of prostaglandins (PGs) and also interfere with tumor growth. A new class of NSAID, piroxicam, was added to the feed of MAM-treated rats. When examined 150 days later, there was a significant reduction of tumor-bearing rats and of tumors/rat compared to controls on drug-free feed; and there was no evidence of toxicity.

Animals↗
PubMed1983

Prolonged antitumor effect of indomethacin on autochthonous intestinal tumors in rats.

Intestinal tumors were induced in randomly propagated Lobund Sprague-Dawley rats by dimethylhydrazine dihydrochloride and by methylazoxymethanol acetate. At 14, 63, and 77 days after exposure to a carcinogen, rats were fed, ad libitum, indomethacin in the drinking water (20 mg/liter) for 20 and 40 weeks. The development of intestinal tumors was prevented or retarded significantly compared to that of control animals. Among control rats at 20, 40, and 52 weeks, the numbers of tumors per rat were relatively constant, but the individual tumors were increased in size.

Animals↗
PubMed1982

Induction of prostate adenocarcinomas in Lobund Wistar rats by testosterone.

Prostate adenocarcinomas were induced in Lobund Wistar rats following subcutaneous implants of silastic chambers containing testosterone propionate. The tumors resembled those that developed spontaneously in the Lobund Wistar rats. Tumors were not induced in ACI rats by the same treatment schedule.

Adenocarcinoma↗
PubMed1982

The relationship between DNA and chromosome damage after bleomycin treatment: dose-response measurements.

The molecular basis for chromosome aberration formation has been studied using the sensitive techniques of premature chromosome condensation and DNA alkaline elution. The dose response of Chinese hamster ovary cells to bleomycin treatment at the DNA and chromosome levels was compared. Each DNA elution curve showed a 2-component profile, with a more sensitive component apparent at low doses. The chromosome aberration curves also exhibited a 2-component profile when determined in G2-PCC; however, this phenomenon was less apparent when chromosome damage was enumerated in mitotic figures. These results suggest that differential sensitivity to bleomycin exists within the cellular chromatin. The effect of dose rate on aberration formation was examined by administering bleomycin at 2 concentrations that, with different treatment times, yielded equivalent amounts of DNA damage. The chromatid exchange rate was independent of dose rate, suggesting that rapidly repaired DNA lesions are not involved in the formation of exchanges.

Animals↗
PubMed1982

Detection of gamma glutamyl transpeptidase in the livers of germfree and conventional rats.

Germfree and conventional rats, 1-41 months of age, were examined for gamma glutamyl transpeptidase in frozen sections prepared from their livers. This histochemical marker has been associated with early changes which develop following exposure to known carcinogenic agents. Positive gamma glutamyl transpeptidase markers were detected in 86% of germfree rats over 4 months of age, and the gamma glutamyl transpeptidase foci were larger and more numerous as the animals aged, and the foci were prominent in rats with hepatic tumors. Gamma glutamyl transpeptidase foci were observed in 96% of livers from conventional rats at 11-20 months of age. The agents responsible for induction of the gamma glutamyl transpeptidase foci in the liver were not identified.

Aging↗
PubMed1982

Induction and repair of DNA and chromosome damage by neocarzinostatin in quiescent normal human fibroblasts.

In an attempt to understand better the molecular basis of chromosome aberration formation, neocarzinostatin (NCS)-induced damage and repair were compared at the chromosome and DNA levels. Chromosome damage and repair in quiescent normal human fibroblasts (PA2 and DET 550) were assayed by the premature chromosome condensation technique in which the G1 prematurely condensed chromosomes are condensed and easily enumerated. DNA damage was monitored by neutral DNA elution. NCS induced chromosome breaks directly in the G1 cells; thus, its clastogenic action does not require passage of cells through S phase. The dose-response curve for NCS-induced damage suggested a two-hit-type event in the formation of chromosome breaks. The half-time of chromosome repair was approximately 4.5 hr, and all but one of the chromosome breaks were repaired by 46 hr. Neither 1-beta-D-arabinofuranosylcytosine nor cycloheximide blocked the repair of either DNA or chromosome damage induced by NCS in quiescent human cells.

Antibiotics, Antineoplastic↗