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Biomedical subjects

R B Franklin

Publications and source records attributed to R B Franklin.

At least 91 records · Page 5Linked to original sources
PubMed1982

Development of a transplantable model of pancreatic duct adenocarcinoma.

We report here the first development of a continuous cell line in tissue culture of an animal pancreatic duct adenocarcinoma that is histologically similar to human pancreatic duct adenocarcinoma. A primary pancreatic duct adenocarcinoma, induced in a male Syrian golden hamster after 23 weeks of weekly subcutaneous injection of N-nitrobis (2-hydroxypropyl)amine, was minced and injected subcutaneously into three hamsters. After 8 weeks, a single tumor was apparent. Subsequent passages of fragments into the cheek pouches were performed at 3- to 4-week intervals. After five passages, minced fragments of a tumor were placed in tissue culture. Colonies appeared by 7 days; an epitheloid cell line, without fibroblasts, was established by 60 days. Single-cell suspensions, injected into hamster cheek pouches or subcutaneously, produced tumors in a dose-dependent fashion. Spent culture medium of tissue culture cells and saline extracts of freshly excised tumors contained pancreatic oncofetal antigen-like activity.

Adenocarcinoma↗
PubMed1981

Alterations in hepatic mixed-function oxidase activity of rainbow trout after acute treatment with polybrominated biphenyl isomers and FireMaster BP-6.

The effects of FireMaster BP-6 and several pure isomers on hepatic microsomal mixed-function oxidase (MFO) activity in rainbow trout have been investigated. After one parenteral injection of these agents at 150 mg/kg and sacrifice 5 d later, there was no elevation of hepatic cytochrome P-450. The noncoplanar isomers 2,4,5,2',4',5'-hexa and 2,3,4,5,2',4',5'-heptabromobiphenyl did not increase any MFO activity generally associated with an increase in cytochrome P-450 levels, including the dealkylations of ethoxycoumarin and benzphetamine. The coplanar isomer 3,4,5,3',4',5'-hexabromobiphenyl produced an increase in O-deethylation of both ethoxycoumarin and ethoxyresorufin, suggesting enhancement of cytochrome P-448 associated activity, but produced no increase in benzphetamine N-dealkylation. The "mixed inducer" 2,4,5,3',4',5'-hexabromobiphenyl, produced a small but insignificant elevation of cytochrome P-448 associated MFO activities and no increase in cytochrome P-450 associated activities. At both 150 and 500 mg/kg, the commercial mixture of polybrominated biphenyls FireMaster BP-6 produced marked elevations of both ethoxycoumarin and ethoxy-resorufin dealkylations but had no effect on demethylation of benzphetamine. When microsomes from rainbow trout treated with FireMaster BP-6 were examined electrophoretically, A coomassie Blue-staining band at 57,000 daltons was intensified, as seen after treatment of fish with the cytochrome P-448 inducer beta-naphthoflavone. It is concluded that coplanar polybrominated isomers produce an induction of hepatic cytochrome P-448 associated activity, while noncoplanar isomers are ineffective as inducers of cytochrome P-450 related MFO activities in rainbow trout.

Animals↗
PubMed1981

Aconitase activity, citrate oxidation, and zinc inhibition in rat ventral prostate.

Aconitase activity and citrate oxidation were determined in mitochondrial preparations from rat ventral prostate. Aconitase activity in prostate mitochondria was approximately 10% of the activity observed in kidney preparations. The prostate aconitase activity was completely inhibited by the addition of 1.0 mmol/l zinc and kidney aconitase was inhibited by approximately 50%. The presence of 1.0 mmol/l zinc also markedly inhibited the formation of isocitrate from cis-aconitate. The reduction of NADP by citrate was markedly inhibited (approx. 95%) by 1.0 mmol/l zinc as compared with a 70 and 40% inhibition of aconitate--and isocitrate--stimulated reduction, respectively. These results indicate that zinc might be a strong inhibitor of aconitase activity with an inhibitory effect on isocitrate dehydrogenase also. The effect of 1.0 mmol/l zinc on citrate oxidation was studied by determining 14CO2 production from 6-14C-citrate. 14CO2 was significantly inhibited by zinc. These results further corroborate the conclusion that citrate accumulation in prostate might be the result of limited citrate oxidation which results from a combination of low aconitase activity and possibly zinc inhibition.

Aconitate Hydratase↗
PubMed1980

Citrate synthesis from fatty acids and amino acids in rat ventral prostate.

The source of the remarkably high citrate level of prostate was investigated in prostate fragments. L-Aspartate and alpha-keto-glutarate formed oxaloacetate through transamination. Neither pyruvate nor acetate was as effective as palmitate in increasing the citrate level. The result suggested that the source of citrate in rat ventral prostate is oxaloacetate from amino acid transamination and acetyl CoA from fatty acid oxidation. Furthermore, the result indicated that carbohydrates contribute little to citrate production in ventral prostate.

Acetyl Coenzyme A↗
PubMed1980

Comparative aspects of the disposition and metabolism of xenobiotics in fish and mammals.

The number of studies in aquatic toxicology has rapidly increased due to the importance of fish as a food source and also because of the increasing awareness of long-term health hazards of aquatic pollution of humans as well as to aquatic flora and fauna. The bioaccumulation and persistence of certain chemicals in fish have been studied for some time but with the characterization of an active hepatic mixed function oxidase system, comparable in many respects to that found in mammals, the role of metabolism in the disposition, toxicity, and persistence of certain chemicals can be studied. The recent observation that rainbow trout and their eggs are very sensitive to aflatoxin B1, a carcinogen that apparently must be activated to a chemically reactive intermediate to exert its effect, has led to the development of fish being considered appropriate animal models for toxicity testing. Since most predictive toxicology in the past has been restricted to nonaquatic species, this review has attempted to describe some of the similarities and dissimilarities between mammals and fish in terms of absorption, distribution, metabolism, and excretion of xenobiotics.

Animals↗
PubMed1978

Effect of aminoglutethimide on blood pressure and steroid secretion in patients with low renin essential hypertension.

An inhibitor of adrenal steroid biosynthesis, aminoglutethimide, was administered to seven patients with low renin essential hypertension, and the antihypertensive action of the drug was compared with its effects on adrenal steroid production. In all patients aldosterone concentrations in plasma and urine were within normal limits before the study. Mean arterial pressure was reduced from a pretreatment value of 117+/-2 (mean+/-SE) mm Hg to 108+/-3 mm Hg after 4 days of aminoglutethimide therapy and further to 99+/-3 mm Hg when drug administration was stopped (usually 21 days). Body weight was also reduced from 81.6+/-7.2 kg in the control period to 80.6+/-7.0 kg after 4 days of drug treatment and to 80.1+/-6.7 kg at the termination of therapy. Plasma renin activity was not significantly increased after 4 days of treatment but had risen to the normal range by the termination of aminoglutethimide therapy. Mean plasma concentrations of deoxycorticosterone and cortisol were unchanged during aminoglutethimide treatment whereas those of 18-hydroxydeoxycorticosterone, progesterone, 17alpha-hydroxyprogesterone, and 11-deoxycortisol were increased as compared to pretreatment values. In contrast, aminoglutethimide treatment reduced mean plasma aldosterone concentrations to about 30% of control values. Excretion rates of 16beta-hydroxydehydroepiandrosterone, 16-oxo-androstenediol, 17-hydroxycorticosteroids and 17-ketosteroids, and the secretion rate of 16beta-hydroxydehydroepiandrosterone were not significantly altered by aminoglutethimide treatment whereas the excretion rate of aldosterone was reduced from 3.62+/-0.5 (mean+/-SE) in the control period to 0.9+/-0.2 mug/24 h after 4 days and to 1.1+/-0.3 mug/24 h at the termination of aminoglutethimide treatment. The gradual lowering of blood pressure and body weight during aminoglutethimide therapy is consistent with the view that the antihypertensive effect of the drug is mediated through a reduction in the patients' extracellular fluid volume, probably secondary to the persistent decrease in aldosterone production. The observation that chronic administration of aminoglutethimide lowered blood pressure in these patients and elevated their plasma renin activity to the normal range without decreasing production of the adrenal steroids, deoxycorticosterone, 18-hydroxydeoxycorticosterone, and 16beta-hydroxydehydroepiandrosterone, makes it unlikely that these steroids are responsible either for the decreased renin or the elevated blood pressure in patients with low renin essential hypertension.

18-Hydroxydesoxycorticosterone↗
PubMed1978

Isocitrate uptake and citrate production by rat ventral prostate fragments.

Prostatic aconitase was investigated utilizing fragments of rat ventral prostate. The rate of citrate formation from isocitrate was used as an index of aconitase activity. Inhibition of citrate formation from isocitrate by fluorocitrate indicated that aconitase activity was being measured. The results indicated that whereas both kidney and prostate formed citrate from isocitrate, the aconitase activity of prostate was independent of both medium isocitrate and citrate concentration. In addition the aconitase activity of prostate seemed to favor citrate formation to a much greater degree than kidney. The results showed that the aconitase catalyzed conversion of citrate to isocitrate is limited in prostate and suggested that the deficient citrate oxidation observed in prostate is the result of a unique aconitase activity.

Aconitate Hydratase↗
PubMed1977

Citrate uptake and oxidation by fragments of rat ventral prostate.

Citrate oxidation was studied utilizing an in vitro preparation of rat ventral prostate which was very similar, with respect to citrate metabolish, to the intact prostate. The rate of citrate oxidation was very slow in comparison to kidney, although citrate entered prostatic tissue and accumulated intracellularly. Citrate was converted to isocitrate at a rate which resulted in a constant citrate/isocitrate ratio over a 10-fold variation in medium citrate concentration. The prostate oxidized significantly more alpha-ketoglutarate and malate than citrate. These results suggested that limited citrate oxidation could account for the accumulation of high prostatic citrate levels.

Animals↗
PubMed1977

Comparative metabolism of the amphetamine drugs of dependence in man and monkeys.

The use of animal models to study drug dependence and tolerance requires that the species used metabolizes the drugs like man, a condition frequently not fulfilled by non-primate species. The metabolic fate of several amphetamine drugs, namely amphetamine, norephedrine, chlorphentermine and phenmetrazine, in the rhesus monkey and the tamarin and two non-primate species has been investigated and compared to that found for man. The findings show that the two primate species metabolize these drugs in a manner similar to that in man.

Amphetamines↗