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Biomedical subjects

R A Arend

Publications and source records attributed to R A Arend.

11 recordsLinked to original sources
PubMed1995

Tryptophan metabolism in chronic inflammatory lung disease.

Induction of indoleamine 2,3-dioxygenase (IDO), an enzyme expressed by mononuclear phagocytes and some fibroblast cell lines in response to interferon-gamma, leads to enhanced degradation of tryptophan to kynurenine. Because inflammatory lung diseases are generally associated with activation of pulmonary macrophages, we investigated tryptophan metabolism in patients with interstitial lung disease by measuring circulating levels of tryptophan and kynurenine in peripheral blood and by measuring the IDO activity of bronchoalveolar cells. IDO activities were increased for bronchoalveolar lavage (BAL) cells obtained from patients with interstitial lung disease (115.4 +/- 30.4, n = 37) when compared with BAL cells from normal subjects (15.2 +/- 7.4, n = 14; p < 0.05), and messenger RNA for IDO was present in BAL cells from patients with interstitial disease but was not present in BAL cells from normal volunteer subjects. Patients with inflammatory lung disease also had decreased tryptophan and increased kynurenine concentrations in serum. The ratio of serum tryptophan levels to serum kynurenine levels was significantly depressed for patients with idiopathic pulmonary fibrosis (18.4 +/- 1.7, n = 29; p < 0.0001), patients with fibrosing alveolitis associated with collagen vascular disease (13.1 +/- 1.6, n = 18; p < 0.0001), or patients with sarcoidosis (21.0 +/- 1.1, n = 50; p < 0.0001), as compared with the ratio for normal subjects (31.8 +/- 2.3, n = 18). Patients with fibrotic disease had the highest levels of BAL cell IDO activity, and patients with collagen vascular disease associated fibrosing alveolitis had the most depressed levels of serum tryptophan and the greatest elevations in serum kynurenine. Measurement of tryptophan and kynurenine concentrations in serum may provide a useful measure of disease activity in chronic inflammatory parenchymal lung diseases such as sarcoidosis and idiopathic pulmonary fibrosis.

Actins↗
PubMed1994

Interferon gamma induced production of indoleamine 2,3 dioxygenase in cultured human synovial cells.

OBJECTIVE: Synovial membrane cells from inflamed joints share morphological and functional properties with malignant mesenchymal cells. Interferon gamma (IFN-gamma) has antitumor cell activity related to stimulation of 2,3 indoleamine dioxygenase (IDO), a widely distributed tryptophan catabolizing enzyme. Our objective was to measure synoviocyte IDO production to determine if the varied clinical and in vitro effects of IFN-gamma on nonmalignant immunocompetent cells might involve a similar mechanism. METHODS: Using an established radioenzymatic assay, we measured IDO activity in suspensions of freshly isolated cells obtained by enzymatic dispersion of human synovial membrane, and in fresh and longterm (> or = 2 months) cultures of these cells in response to varying concentrations of recombinant human interferons alpha 2a, beta ser, or gamma. RESULTS: In fresh and in > or = 2 month-old cultures, IFN-gamma strongly stimulated IDO activity, a corresponding fall in supernatant tryptophan levels, and an elevation in the supernatant concentration of kynurenine, tryptophan's principal metabolite, mRNA for IDO was likewise markedly increased in cells after 4 days' incubation with IFN-gamma. Staining studies indicated that the IDO producing cells in synovium were not typical macrophages. Interferon beta ser had weak IDO stimulatory activity that was in a few cases additive to that of IFN-gamma. In no case did interferon beta ser abrogate IFN-gamma induced IDO activity increases. Interferon alpha 2a also had weak stimulatory activity. CONCLUSIONS: IFN-gamma stimulates IDO production and tryptophan metabolism in cultured human synovial cells, and therefore may contribute to this cytokine's in vitro and clinical effects in arthritis and inflammation.

Cells, Cultured↗
PubMed1986

beta-Glucuronidase and hyperbilirubinaemia in breast-fed and formula-fed babies.

Breast milk or formula milk and serum samples from 34 breast-fed babies, 15 formula-fed babies, and their mothers were examined at 3 and 21 days of neonatal age. Infant faecal samples were obtained on day 21 only. At both ages serum total bilirubin concentrations were significantly higher in breast-fed than in formula-fed infants. Beta-glucuronidase activity in formula milk was negligible while that in human milk was considerable. Day 21 faecal beta-glucuronidase was higher in the breast-fed babies. In the breast-fed babies, serum bilirubin levels were related to concentrations of beta-glucuronidase in breast milk on both days 3 and 21 and to levels of faecal beta-glucuronidase on day 21. In 4 additional babies whose feeds were temporarily changed from breast milk to formula milk because of hyperbilirubinaemia there was a striking decrease in faecal beta-glucuronidase activity coincident with a fall in serum bilirubin. Breast milk beta-glucuronidase seems to be an important factor in the neonatal hyperbilirubinaemia of breast-fed babies.

Adult↗
PubMed1980

The kynurenine load test, an adjunct to the tryptophan load test.

The kynurenine load test was introduced to distinguish, in vivo, between abnormal tryptophan metabolism caused by induction of tryptophan oxygenase or by impaired kynureninase function. This test was carried out by giving a loading dose of 700 mumol L-kynurenine sulphate followed by determination of urinary metabolites of the tryptophan-nicotinic acid ribonucleotide pathway. The results of the kynurenine load test in a group of healthy post-menopausal female subjects show a consistant increase in urinary excretion of some metabolites of the tryptophan-nicotinic acid ribonucleotide pathway (kynurenine, 3-hydroxy-kynurenine, and 3-hydroxyanthranilic acid) of a magnitude comparable to the increase seen after a loading dose of 9800 mumol L-tryptophan (the tryptophan load test).

3-Hydroxyanthranilic Acid↗
PubMed1980

Effect of natural oestrogens on tryptophan metabolism: evidence for interference of oestrogens with kynureninase.

Urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway, urinary excretion of 4-pyridoxic acid and blood concentrations of oestradiol and pyridoxal phosphate were studied in groups of post-menopausal women before or during treatment with natural oestrogens, i.e. oestradiol and oestriol, before and after loading doses of 9800 mumol L-tryptophan or 700 mumol L-kynurenine sulphate. Natural oestrogens induced abnormalities of tryptophan metabolism similar to those induced by synthetic oestrogens, and there was a dose related increase in urinary excretion of metabolites of the tryptophan-nicotinic acid ribonucleotide pathway before the kynureninase step. The increase in urinary excretion of these metabolites also after a loading dose of 700 mumol L-kynurenine indicates an inhibitory effect of oestrogens on kynureninase in vivo. Evidence is presented that this inhibition is an effect mediated through decreased availability of vitamin B6, the coenzyme of kynureninase, although the possibility of a direct effect of oestrogens on kynureninase can not be excluded.

Aged↗
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↗
PubMedDate not supplied

Effects of anesthetic agents on bile pigment excretion in the rat.

Anesthesia-induced alterations in bilirubin conjugation were studied. Rats were fitted with bile duct and jugular vein catheters while anesthetized with diethyl ether, ketamine or pentobarbital. As anesthesia abated, bile was collected for the next 5 hr and analyzed for flow rate, total bilirubin excretion and bilirubin glucuronide composition. The high-performance liquid chromatography method used allowed direct analysis of bile without derivatization or extraction. Ether anesthesia was associated with a reversible suppression of diglucuronide formation and total bilirubin excretion, with reciprocal monoglucuronide changes. Bile flow and pigment excretion were variable with ketamine. Pentobarbital provided the most uniform excretion data, although the ratio of C-8:C-12 monoglucuronide varied with all drugs. These data are consistent with recently reported drug-induced alterations in hepatic uridine diphosphoglucuronic acid concentration and support the hypothesis that alterations in this substrate concentration are capable of influencing rates of hepatic glucuronide formation.

Anesthetics↗