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Biomedical subjects

G T Bryan

Publications and source records attributed to G T Bryan.

At least 73 records · Page 4Linked to original sources
PubMed1981

Protective effect of nicotinamide on bracken fern induced carcinogenicity in rats.

Albino noninbred weanling male and female rats were fed a basic grain diet (Group 1), a basic diet supplemented with 0.5% nicotinamide (Group 2), a basic diet containing 33% bracken fern (BF) (Group 3), or a basic diet supplemented with 33% BF and 0.5% nicotinamide (Group 4) for 58 weeks. Dietary nicotinamide decreased the BF-induced incidence of both intestinal and bladder tumorigenesis by about 40%. The inhibitory effect of nicotinamide on the BF-induced intestinal and bladder tumors was significant at p less than 0.05 and p less than 0.01, respectively.

Animals↗
PubMed1981

Mutagenicity, carcinogenicity, distribution, and nitroreduction of 4-(5-nitro-2-furyl)thiazole in the rat.

Albino noninbred weanling female Sprague-Dawley rats were fed a powdered basic grain diet (Group 1) or a basic diet supplemented with 1540 ppm of 4-(5-nitro-2-furyl)thiazole (NFT) (Group 2). Group 2 rats consumed an estimated mean NFT cumulative dose of 42 mmol/rat, exhibited significant growth retardation and hepatomegaly, and displayed 46 neoplasms (24 multiple mammary fibroadenomas, 19 forestomach squamous cell carcinomas, and 3 other malignant tumors) in 31 of 35 rats histologically evaluated. Six of 36 control rats had solitary, benign mammary fibroadenomas. After p.o. administration of NFT, extraction of urine with chloroform:diethyl ether followed by gas chromatography provided a major peak with a retention time of about 4 min. Catalytic hydrogenation of NFT with palladium on activated carbon afforded a product with the same retention time. The isolated urinary metabolite of NFT exhibited mass spectral fragmentation patterns and gas and high-pressure liquid chromatographic retention times similar to those of the chemical reduction product. These data demonstrate the identical chemical characteristics of the in vivo urinary metabolite of NFT and the compound obtained by chemical reduction of NFT. Spectroscopic analyses established the structural identity of this reduced product as 1-(4-thiazolyl)-3-cyano-1-propanone. Forty-eight hr after the intragastric administration of [14C]NFT, 32% of radioactivity was recovered in urine, 57% was recovered in gastrointestinal contents and feces, and 5.5% was recovered in expired 14CO2. About 2% of the urinary radioactivity was extracted in chloroform:diethyl ether, suggesting that 1-(4-thiazolyl)-3-cyano-1-propanone is quantitatively a minor urinary metabolite of NFT. 1-(4-Thiazolyl)-3-cyano-1-propanone was 1.1 x 10(4)-fold less active than was NFT in the Ames mutagenicity assay with Salmonella typhimurium TA 100.

Animals↗
PubMed1981

Early induction of rat colonic epithelial ornithine and S-adenosyl-L-methionine decarboxylase activities by N-methyl-N'-nitro-N-nitrosoguanidine or bile salts.

The responses of male noninbred rat colonic epithelial ornithine decarboxylase (EC 4.1.1.17) (ODC) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) (SAMD) activities following topical administration of N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) or bile salts were studied. A single intrarectal installation of 13 mumol of MNNG resulted in a significant (p < 0.001) 20-fold peak ODC activity after 4 hr, with a prompt return to control levels by 12 hr. Stimulation of SAMD activity was less pronounced but significant (p < 0.01), with a broad 2-fold peak over controls. No significant responses of colonic epithelial enzyme activities were detected following a single intrarectal instillation of N-methyl-N'-nitroguanidine, a noncarcinogenic and nonmutagenic metabolite of MNNG, at a dose equimolar to that of MNNG. Bile salts significantly (p < 0.001) induced ODC with almost the same kinetic pattern as that observed after MNNG administration in the following order: sodium deoxycholate > sodium chenodeoxycholate > sodium cholate. Activations of SAMD were similar for these 3 bile salts. Glycine- or taurine-conjugated deoxycholate showed ODC and SAMD enzyme activations similar to that of nonconjugated deoxycholate. No significant enzyme response was seen after sodium dehydrocholate treatment. Stimulation of activities of both enzymes was directly dependent on bile salt dose. Induced ODC and SAMD activities were principally localized in colonic epithelium. Deoxycholate-stimulated enzyme activities were significantly inhibited by cycloheximide. Enzyme stimulations by active compounds were accompanied by morphological changes such as mucosal cell degeneration, mucus depletion, submucosal congestion, and punctate hemorrhage, followed by submucosal leukocytic cellular infiltration. These data support the concept that initiating and promoting events may be involved in colon carcinogenesis.

Adenosylmethionine Decarboxylase↗
PubMed1980

Role of N-acetyltransferase phenotype in human susceptibility to bladder carcinogenic arylamines.

N-acetyltransferase activity is species-specific and in animal experiments a determinant of the susceptibility of each species to arylamine bladder carcinogens. The effect of N-acetylation is that of inactivation. In humans, N-acetyltransferase activity is also genetically determined so that two N-acetyltransferase phenotypes exist, a rapid acetylator phenotype and a slow acetylator phenotype. N-acetyltransferase phenotype was determined in 71 bladder cancer patients and in 74 control subjects from Copenhagen. The distribution of the slow acetylator phenotype among the bladder cancer patients was 65% in control to 51% among the control subjects, indicating that the N-acetyltransferase phenotype also in humans may be a determinant of the susceptibility of each individual to arylamine carcinogens. In addition, this finding indicates that carcinogenic arylamines also play a role in bladder carcinogenesis in Copenhagen. Such studies may identify risk groups in a population and may reveal geographical areas with arylamine induced bladder cancer.

Acetylation↗
PubMed1980

Carcinogenicity of tannin and tannin-free extracts of bracken fern (Pteridium aquilinum) in rats.

F344 inbred and Sprague-Dawley noninbred rats were fed a basic diet (groups 1 and 7) or a basic diet supplemented with 0.1% (later, 0.2 and 0.4%) tannin (group 2) isolated from bracken fern (Pteridium aquilinum) (BF), 33% BF (groups 3 and 6), 2% chloroform fraction of BF (group 4), or 4% tannin-free fraction of BF (group 5). The following incidences of intestinal or bladder tumors were observed: group 1, intestinal and bladder, 0/16; group 2, 0/21; group 7, 0/16; groups 4 and 5, intestinal, 7/15, bladder, 0/15; group 3, intestinal, 19/20, bladder, 12/20; and group 6, intestinal, 22/30, bladder, 15/30. The chloroform-methanol fraction prepared from urine of rats fed BF, chloroform fraction of BF, or tannin-free fraction of BF demonstrated mutagenicity for Salmonella typhimurium TA 100 but not for TA 98. No mutagenicity was detected in other prepared fractions. F344 rats in group 8 received weekly sc injections of tannin solution (0.1 g/kg body wt) for 38 weeks, and 16/20 developed palpable tumors that were malignant fibrous histiocytomas at the injection site. No tumor was present in any rat of control group 9.

Animals↗
PubMed1980

Early induction of mouse urinary bladder ornithine decarboxylase activity by rodent vesical carcinogens.

The responses of mouse urinary bladder ornithine decarboxylase (EC 4.1.1.17) and S-adenosyl-L-methionine decarboxylase (EC 4.1.1.50) activities were studied following topical intravesical administration of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide (FANFT) or 2-amino-4-(5-nitro-2-furyl)thiazole (ANFT), potent rodent bladder carcinogens. A single bladder topical application of ANFT or FANFT resulted in a significant increase over controls of ornithine decarboxylase activity within 5 hr, with a return to control levels by 10 hr. S-Adenosyl-L-methionine decarboxylase activity demonstrated a lesser response to topical ANFT or FANFT, achieving a level 2 or 3 times that of controls at 5 to 8 hr, followed by a gradual decline to control levels. Stimulation of activities of both enzymes was dose dependent over a range of 4.6 to 460 nmol of ANFT. ANFT-induced ornithine decarboxylase activity was principally localized in the bladder epithelium and was inhibited in a linear dose-response relationship by the synthetic retinoid, 13-cis-retinoic acid. Mice given FANFT p.o. demonstrated a significant increase over controls in ornithine decarboxylase activity within 12 hr, followed by a gradual decline to control levels by 72 hr.

Adenosylmethionine Decarboxylase↗
PubMed1980

Quercetin, a rat intestinal and bladder carcinogen present in bracken fern (Pteridium aquilinum).

Albino noninbred weanling male and female rats were fed a basic grain diet (Group 1) or a basic diet supplemented with 33% bracken fern [BF (Group 2)] or 0.1% quercetin [purity, > 99% (Group 3)] for 58 weeks. The quantities of quercetin and kaempferol (a close structural analog) in BF as glycosides were determined to be 0.57 and 1.1 g, respectively, per kg of dried BF. Estimated mean total cumulative doses (mmol) per rat were: Group 1, quercetin, males and females < 0.03; kaempferol, males and females < 0.03; Group 2, quercetin, males 5.8, females 5.2; kaempferol, males 11.9, females 10.8; and Group 3, quercetin, males 27.8, females 25.3; kaempferol, males and females < 0.03. Growth of rats fed BF or quercetin was comparable but significantly (p < 0.01) slower after 24 weeks than that of Group 1. Mean survivals (weeks) of rats of all groups were: Group 1, 58 +/- 7 (S.D.); Group 2, 51 +/- 13; and Group 3, 56 +/- 8. They were not significantly different, although rats fed BF tended to die earlier secondary to intestinal tumor-induced intussusception and obstruction. The following incidences of intestinal or bladder neoplasms in male or female rats, respectively, were observed: Group 1, intestinal and bladder, males, 0 of 9, females, 0 of 10; Group 2, intestinal, males, 7 of 8, females, 10 of 11; bladder, males, 6 of 8, females 8 of 11; Group 3, intestinal, males, 6 of 7, females, 14 of 18; bladder, males, 2 of 7, females, 3 of 18. The histopathology of neoplasms of the 2 target organs was identical for rats of Groups 2 and 3. Multiple ileal intestinal neoplasms of rats fed quercetin included: adenoma, 4; fibroadenoma, 7; and adenocarcinoma, 9 (with mesenteric metastases, 3). The 5 bladder tumors were papillary or sessile transitional cell carcinomas.

Adenocarcinoma↗
PubMed1979

The use of plasma androstenedione in monitoring therapy of patients with congenital adrenal hyperplasia.

Therapy of congenital adrenal hyperplasia tranditionally is monitored by the amount of urinary 17-KS. However, 24-hour urine collections are difficult to obtain and are often unreliable. Measurement of the plasma concentrations of androgens, such as delta or T, would therefore be a more convenient way to determine the efficacy of treatment. Over a period of 2 to 24 months, 23 patients were periodically assessed by clinical examination, bone age, and determinations of plasma delta, plasma T, and 24-hour urinary 17-KS. Plasma T concentration correlated well with clinical control in females and in preadolescent males, but not in infant and pubertal males. By contrast, plasma delta concentration correlated well with clinical control in either sex, regardless of stage of puberty. The present study suggests that monitoring plasma delta concentration is useful in the long-term management of patients with CAH.

17-Ketosteroids↗
PubMed1979

Hypertension in children: endocrine aspects.

Hypertension in children is a rare disorder with reliable estimates of annual incidence that do not exceed 0.1%. At least one third of these cases have no definable etiology when all of the presently available diagnostic studies are used. Major invasive or expensive evaluations are indicated when hypertension is sustained or severe, and should be directed toward the renal and renovascular areas. Serum potassium and calcium estimates are essential in every case, but the more extensive evaluations of thyroid, parathyroid, adrenal cortical and adrenal medullary hormones should be reserved for patients with specific indications of malfunction in those systems.

Adrenal Gland Diseases↗
PubMed1979

N-acetyltransferase phenotype and risk in urinary bladder cancer: approaches in molecular epidemiology. Preliminary results in Sweden and Denmark.

A variable but often significant proportion of urinary bladder cancer in urban areas can be attributed to occupational and cultural (cigarette smoking) situations associated with exposures to various arylamines. The variable N-acetylation of carcinogenic arylamines by human hepatic enzyme systems, the known genetic regulation and polymorphic distribution of this enzyme activity in humans, and the known enhanced susceptibility of individuals with the genetically-distinct "slow acetylator" phenotype to various arylamine toxicities, has prompted examination of possible correlations between N-acetyltransferase phenotype and urinary bladder cancer risk in rural and urban populations. In this context, N-acetylation is viewed as a component of detoxication pathways with respect to arylamine bladder carcinogenesis. In preliminary utilizations of this approach, a population of urban urinary bladder cancer patients from Copenhagen, Denmark displayed a 13% excess (p = 0.065) of individuals with the slow acetylator phenotype (46/71 = 64.8%) when compared to a Danish control population (38/74 = 51.4%). These data are consistent with the possibility that arylamines may play an etiological role in bladder cancer in this locale and that slow acetylator individuals may be at higher relative risk (1.74) than rapid acetylator individuals. As 95% of patients reported histories of smoking, it was not possible to isolate and examine smoking factors. In contrast, a population of rural urinary bladder cancer patients from Lund, Sweden, where bladder cancer incidence (20/100,000) (1971) is lower than in Copenhagen (43.8/100,000) (1968-72), no difference in slow acetylator distribution was observed between bladder cancer (80/115 = 69.6%) and Swedish control (79/118 = 66.9%) populations, indicating a relative lack of involvement of arylamines in the etiology of rural bladder cancer. Populations of "spontaneous" bladder cancer patients would be expected to contain variable portions of disease related to arylamine exposure and would be less likely to display a detectable correlation than would an industrial population with documentable arylamine exposure. Consequently, confirmation of this hypothesis is being pursued by examination of industrial populations in an effort to obtain an empirical estimate of relative risk for slow and rapid acetylator phenotypes. These studies involve exposure-matched workmen both with and without bladder cancer.

Acetyltransferases↗