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Biomedical subjects

R R Brown

Publications and source records attributed to R R Brown.

At least 109 records · Page 6Linked to original sources
PubMed1979

Tryptophan metabolism in bladder cancer patients from Copenhagen.

Urinary excretion before and after a loading dose of tryptophan, plasma pyridoxal phosphate concentration and urinary excretion of 4-pyridoxic acid was studied in 44 male bladder cancer patients from Copenhagen. Six patients (14%) had abnormal tryptophan metabolism, decreased plasma pyridoxal phosphate concentration and in most cases low urinary excretion of 4-pyridoxic acid indicating decreased availability of vitamin B6 or decreased formation of pyridoxal phosphate from vitamin B6. It is concluded that abnormal tryptophan metabolism only plays a minor role for bladder cancer carcinogenesis in Copenhagen. It is, however, stressed that such studies do not rule out the possibility that the aromatic degradation products of tryptophan may be cocarcinogens or promotors as other studies have indicated.

Denmark↗
PubMed1977

Vitamin B6 deficiency in cancer patients.

The plasma pyridoxal phosphate concentration was determined in 30 cases of early breast cancer, 21 patients with locally recurrent disease, and 43 patients with systemic metastases. The two groups of advanced breast cancer had significantly lower plasma pyridoxal phosphate levels than 36 healthy women of similar age. Urinary 4-pyridoxic acid excretion was normal in breast cancer. Plasma pyridoxal phosphate concentrations were also reduced in 34 women with widespread cancer derived from primary sites other than breast, but were normal in 39 with early disease.

Adult↗
PubMed1977

Metabolism of methionine in oral contraceptive users and control women receiving controlled intakes of vitamin B6.

The metabolism of methionine was studied in 10 control and in 14 women using estrogen-containing oral contraceptives during 28 days of vitamin B6 deficiency and then for another 28 days while ingesting the same diet with daily supplements of 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride. Urinary cystathionine excretion after a 3-g load of L-methionine increased promptly in both groups and continued to increase throughout the 28 days of vitamin B6 depletion; there was no significant difference in the amount excreted by controls and oral contraceptive users. Two milligrams of pyridoxine-HCl restored the cystathionine excretion to predepletion levels within three to four weeks for both control and oral contraceptive users. Daily supplements of 0.8 mg of pyridoxine-HCl for as long as four weeks failed to restore cystathionine excretion to normal levels for either controls or contraceptive users; supplements of 2.0 mg met the vitamin B6 requirements for both groups. Urinary methionine, cysteine sulfinic acid, and taurine excretion did not differ significantly between the two groups at any time. The data indicate that oral contraceptive users are not generally different from non-users with respect to vitamin B6 requirements as evidenced by methionine metabolism.

Adult↗
PubMed1977

Effects of vitamin B-6 deficiency and tryptophan loading on urinary excretion of tryptophan metabolites in mammals.

The effect of vitamin B-6 deficiency on excretion of tryptophan metabolites was compared in rats, guinea pigs, hamsters, and humans. With adequate vitamin B-6 intake, a high percentage of the tryptophan administered was excreted as kynurenic acid and quinolinic acid in rat urine, and as acetylkynurenine and kynurenine in hamster urine. None of the tryptophan metabolites measured in normal guinea pig urine or human urine accounted for more than 1% to 2% of the tryptophan administered. During vitamin B-6 deficiency, the percentages of the tryptophan load excreted as xanthurenic acid, kynurenine, and o-hydroxykynurenine, (which precede the 3-hydroxykynureninase step in the kynurenine pathway) were increased in all four species. However, the percentages excreted as 3-hydroxyanthranilic acid and quinolinic acid, which are beyond the 3-hydroxy-kynureninase step, responded differently. The 3-hydroxyanthranilic acid percentage was not changed in rat urine, but was increased in human and guinea pig urines. The quinolinic acid percentage was decreased in rat urine, unchanged in guinea pig and hamster urine, and increased in human urine. In rats, depression of 3-hydroxykynureninase activity was apparently the major factor causing a change in the pattern. However, in hamsters, kynurenine hydroxylase and o-hydroxykynureninanse activities apparently were depressed. In humans, 3-hydroxykynureninase activity also was apparently depressed and the total amount of administered tryptophan accounted fro in the urine as metabolites of the kynurenine pathway was increased. Levels of urinary metabolites reached a maximum in guinea pigs after only 1 week of consuming the vitamin B-6 deficient diet, suggesting that the vitamin deficiency developed very rapidly in this species.

Adult↗
PubMed1977

Effect of tryptophan and nicotinamide loads on urinary excretion of RNA metabolites by bladder cancer patients.

In a comparative study of tryptophan metabolism and urinary excretion of nucleic acid derivatives (including beta-aminoisobutyric acid, 7-methylguanine, pseudouridine, and urate) in 12 male bladder cancer patients, the excretion of pseudouridine and 7-methylguanine decreased significantly after an oral dose of 2 g L-tryptophan. A similar decrease occurred after an oral nicotinamide load of 50 mg four times a day, which indicated a possible common mode of action of tryptophan and nicotinamide. No definite resolution could be made as to the causal mechanism for the observed descrase in RNA turnover.

Aminoisobutyric Acids↗
PubMed1976

Effect of oral contraceptives and vitamin B6 supplements on alanine and glycine metabolism.

Plasma alanine or glycine concentrations and blood pyruvate were studied before and after oral administration of the two amino acids to women using estrogen-containing oral contraceptives and to a control group of women. Thirty oral contraceptive users and 14 controls received alanine loads (200 mg/kg of body weight). The two groups had similar fasting plasma alanine levels, but the fasting blood pyruvate was elevated in the contraceptive steroid-treated women. After alanine ingestion, the increases in plasma alanine were significantly lower in the oral contraceptive users. Both groups showed a rise in blood pyruvate; there were no differences in the increments above fasting values. Treatment with pyridoxine hydrochloride, 25 mg for 4 weeks, had not effect on the responses of 11 oral contraceptive users to alanine loading. Twenty-four oral contraceptive users and 14 controls were studied before and after a glycine load (140 mg/kg of body weight). The fasting plasma glycine levels were similar, but lesser increases after ingestion of the amino acid occurred in the oral contraceptive-treated group. Blood pyruvate concentrations in both oral contraceptive users and controls were unaffected by oral glycine loads.

Adult↗
PubMed1976

Experimental biharzial bladder cancer: tryptophan metabolism in nonhuman primates experimentally infected with Schistosoma haematobium.

A nonhuman primate species infected with Schistosoma haematobium provided a model system for controlled studies on biharzial bladder cancer. Urinary excretion of tryptophan metabolites by capuchin monkeys (Cebus apella) was similar to that of humans when expressed per g creatinine. Liver tryptophan oxygenase activity of the capuchin monkeys was comparable to that of humans. Excretion of 3-hydroxykynurenine and 3-hydroxyanthranilic acid was elevated above control levels in capuchin monkeys infected experimentally with S. haematobium. The capuchin-S. haematobium system closely resembles the human biharziasis system and offers a reproducible laboratory model system for the controlled study of the parasitology, pathogenesis, and biochemistry of biharzial bladder cancer.

3-Hydroxyanthranilic Acid↗
PubMed1976

Abnormal tryptophan metabolism in a family with a history of bladder cancer.

Tryptophan metabolism was studied in a family in which a sister and brother had bladder cancer. Urinary tryptophan metabolites after administration of 2 g L-tryptophan were measured in 4 sisters and 1 brother, all free of disease when studied. One sister with and 2 without histories of bladder cancer had significantly elevated levels of kynurenine, acetylkynurenine, and 3-hydroxykynurenine. Administration of 100 mg pyridoxine hydrochloride returned the tryptophan metabolism to normal in these 3 individuals. One brother with a 1 sister without bladder cancer had normal metabolism. A repeat study 2 years later confirmed the abnormal metabolism in the 3 sisters. Two sisters with abnormal tryptophan metabolism were given 200 mg L-kynurenine sulfate orally to bypass the effects of tryptophan oxygenase activity. Both excreted elevated levels of kynurenine and 1 excreted elevated levels of 3-hydroxykynurenine.

Aged↗
PubMed1975

Urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and erythrocyte aminotransferase levels in oral contraceptive users receiving controlled intakes of vitamin B6.

Fifteen women who had used combination type oral contraceptives (estrogen plus progestogen) and 9 control women who had never used these agents were given a diet deficient in vitamin B6. After 1 month, this diet was supplemented daily with 0.8, 2.0 or 20.0 mg of pyridoxine hydrocholride for an additional month. At weekly intervals, measurements were made of urinary 4-pyridoxic acid, plasma pyridoxal phosphate, and erythocyte alanine and aspartate aminotransterases. No significan differences were observed between oral contraceptive users and controls in any of the above measured indices. The data suggest that if the use of oral contraceptives of the combined estrogen-progestogen type does alter the requirement for vitamin B6, the effect is a mild one and of doubtful clinical significance to the majority of women taking these steroid preparations. The amount of vitamin B6 (as pyridoxine) needed to maintain normal levels of the above indices of vitamin B6 nutrition in these subjects were between 0.8 and 2.0 mg/day.

Adult↗
PubMed1975

Vitamin B6 requirements of women using oral contraceptives.

Fifteen women who used combined estrogen-progestogen oral contraceptives and nine control women were given a vitamin B6-deficient diet for 4 weeks and the same diet supplemented with 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride for an additional 4 weeks. At weekly intervals a variety of indices of vitamin B6 nutrition were measured to determine rates of depletion and repletion. The tryptophan load test (2.0 g) was significantly different in the contraceptive users. However, other indices, including urinary cystathionine (3.0 g L-methionine load), urinary 4-pyridoxic acid, plasma phosphate, and erythrocyte alanine and aspartate aminotransferases, were not significantly different. Since altered tryptophan metabolism persisted in contraceptive users even when other indices of vitamin B6 nutrition were normal, we suggest that the use of oral contraceptives specifically affects tryptophan metabolism by some means other than through a vitamin B6 deficiency.

Adult↗
PubMed1975

Effect of oral contraceptives and vitamin B6 deficiency on carbohydrate metabolism.

Oral glucose tolerance, urinary xanthurenic acid excretion, and plasma pyridoxal phosphate concentrations were determined in nine women taking oral contraceptives and in four controls. The tests were repeated after 4 weeks ingestion of a vitamin B6-deficient diet, and again after pyridoxine supplementation. Vitamin B6 deficiency, as judged by an increased xanthurenic acid excretion and reduced plasma pyridoxal phosphate, was associated with a deterioration in the glucose tolerance of the contraceptive steroid-treated group despite normal or elevated plasma insulin levels. This abnormality was reversed by pyridoxine. There was no change in the glucose tolerance of the vitamin B6-deficient controls. The observed pyridoxine-responsive alteration in carbohydrate metabolism may involve the complexing of insulin with xanthurenic acid with a consequent loss of biological activity. In addition, oral contraceptives may enhance gluconeogensis.

Adult↗
PubMed1975

Studies on tryptophan metabolism in Danish bladder cancer patients.

Urinary excretion of metabolites of the kynurenine pathway before and after a loading dose of 2 g L-tryptophan was studied in 31 bladder cancer patients from the Copenhagen area. Only 2 patients (6 per cent) showed abnormal tryptophan metabolism, and both patients excreted increased amounts of only 3-hydroxykynurenine after a loading dose of 2 g L-tryptophan. The percentage of bladder cancer patients with abnormal tryptophan metabolism is compared with the percentage found in other parts of the world. It is suggested that these findings may indicate that tryptophan metabolites do not play a major role in the genesis of bladder cancer among bladder cancer patients from the Copenhagen area. Other etiologic factors should be looked for.

Denmark↗
PubMed1975

Effects of oral contraceptives on tryptophan metabolism and vitamin B6 requirements in women.

To evaluate the effect of oral contraceptive usage on the nutritional requirement for vitamin B6, control women and oral contraceptive users were depleted of vitamin B6 for 1 month followed by a month of repletion with 0.8, 2.0, or 20.0 mg of pyridoxine hydrochloride per day. At weekly intervals a number of indices of vitamin B6 nutrition were measured. Marked elevation in excretion of tryptophan metabolites occurred in oral contraceptive users after tryptophan loads. However, other indices of vitamin B6 nutritional state, including urinary 4-pyridoxic acid excretion, urinary cystathionine excretion, plasma pyridoxal phosphate concentrations, and erythrocyte aspartate and alanine aminotransferases were not different between controls and oral contraceptive users. The excretion of metabolites after oral loading doses of L-kynurenine (which bypasses tryptophan oxygenase) was elevated in oral contraceptive users indicating that abnormal metabolism of tryptophan was not due only to induced tryptophan oxygenase. The data indicate that use of oral contraceptives does not generally change the requirement for vitamin B6 but rather produces a specific change in activity of enzymes beyond kynurenine in the pathway of tryptophan metabolism.

Adult↗