A. Kappas

Publication List Details

Period

1983 - 1999

Number

115

Co-Authors

Mutagenic activity of the antitumour agent homo-aza-steroidal ester of p-N,N-bis(2-chloroethyl)aminophenoxyacetic acid (NSC 294859) in the Salmonella/microsome assay (1993)

Voutsinas, G., Kappas, A., Demopoulos, N.A., Catsoulacos, P.

The mutagenic activity of the new antitumour agent 3β-hydroxy-13α-amino-13,17-seco-5α-androstan-17-oic-13,17-lactam-p-N,N-bis(2-chloroethyl)aminophenoxyacetate (NSC 294859) was studied in the...

Tallysomycin-induced mitotic aneuploidy and point mutations in Aspergillus nidulans (1986)

Demopoulos, N.A., Kappas, A.

Tallysomycin is an antibiotic compound structurally related to bleomycin, and like bleomycins and phleomycins also shows antitumour activity. We have investigated the genetic activity of tallysomycin...

Genotoxic activity of plant growth-regulating hormones in Aspergillus nidulans (1983)

Kappas, A.

Three plant growth-regulating hormones, indole-3-acetic acid (IAA), indole-3-butyric acid (IBA), and kinetin (6-furfuryl-aminopurine), were tested for their genetic activity in Asper-gillus nidulans...

Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity.

Abraham, N G, Lavrovsky, Y, Schwartzman, M L, Stoltz, R A, Levere, R D, Gerritsen, M E, ...

Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and...

Identification of binding sites for transcription factors NF-kappa B and AP-2 in the promoter region of the human heme oxygenase 1 gene.

Lavrovsky, Y, Schwartzman, M L, Levere, R D, Kappas, A, Abraham, N G

Heme oxygenase (HO) is the rate-limiting enzyme in heme catabolism and its activity is induced by many agents, including its substrate heme, heavy metals, UV radiation, and other injurious oxidant...

The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria.

Nakahashi, Y, Fujita, H, Taketani, S, Ishida, N, Kappas, A, Sassa, S

The molecular basis of an inherited defect of ferrochelatase in a patient with erythropoietic protoporphyria (EPP) was investigated. Ferrochelatase is the terminal enzyme in the heme biosynthetic...

Heme inhibits human immunodeficiency virus 1 replication in cell cultures and enhances the antiviral effect of zidovudine.

Levere, R D, Gong, Y F, Kappas, A, Bucher, D J, Wormser, G P, Abraham, N G

The effects of heme alone and heme administered together with 3'-azido-3'-deoxythymidine (AZT) on human immunodeficiency virus replication in human peripheral blood lymphocytes and in the H9 cell...

Interference of Griseofulvin with the Segregation of Chromosomes at Mitosis in Diploid Aspergillus nidulans

Kappas, A., Georgopoulos, S. G.

Low concentrations of the antibiotic griseofulvin were found to cause increased frequencies of somatic segregation due to chromosome nondisjunction in a diploid strain of Aspergillus nidulans.

Regulation of food intake and body weight by cobalt porphyrins in animals.

Galbraith, R A, Kappas, A

Cobalt-substituted protoporphyrin administered subcutaneously to normal adult rats elicited prompt decreases in food intake and sustained decreases in body weight. Repetitive parenteral...

Dual control mechanism for heme oxygenase: tin(IV)-protoporphyrin potently inhibits enzyme activity while markedly increasing content of enzyme protein in liver.

Sardana, M K, Kappas, A

Tin(IV)-protoporphyrin (Sn-protoporphyrin) potently inhibits heme degradation to bile pigments in vitro and in vivo, a property that confers upon this synthetic compound the ability to suppress a...

Induction of a deficiency of steroid delta 4-5 alpha-reductase activity in liver by a porphyrinogenic drug.

Kappas, A, Bradlow, H L, Bickers, D R, Alvares, A P

The hepatic enzymes that catalyze drug oxidations and the reductive metabolism of steroid hormones to 5alpha-derivatives are localized in membranes of the endoplasmic reticulum. Phenobarbital, which...

The cytochrome P-450-depleted animal: an experimental model for in vivo studies in chemical biology.

Drummond, G S, Kappas, A

An experimental method is described to deplete markedly in vivo the cytochrome P-450 content of liver for prolonged periods of time. The method uses the synthetic metalloporphyrin cobalt-heme (cobalt...

Thyroid hormone regulation of heme oxidation in the liver.

Smith, T J, Drummond, G S, Kourides, I A, Kappas, A

The effects of 3,5,3'-triiodothyronine (T3) on heme oxygenase (EC 1.14.99.3) activity and cytochrome P-450 content in liver were examined in thyroidectomized rats. T3, when administered for 5 days at...

Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation.

Drummond, G S, Kappas, A

The effects of various metalloporphyrins on hepatic heme oxygenase (EC 1.14.99.3) activity were examined in order to identify compounds that could inhibit heme degradation to bile pigment and might...

Radiometric analysis of biological oxidations in man: sex differences in estradiol metabolism.

Fishman, J, Bradlow, H L, Schneider, J, Anderson, K E, Kappas, A

The oxidative metabolism of estradiol was studied in normal men and women by a radiometric procedure that provides information on the totality of the biotransformations concerned. The release of 3H...

Studies in porphyria: functional evidence for a partial deficiency of ferrochelatase activity in mitogen-stimulated lymphocytes from patients with erythropoietic protoporphyria.

Sassa, S, Zalar, G L, Poh-Fitzpatrick, M B, Anderson, K E, Kappas, A

In this paper we show that the ferrochelatase defect in erythropoietic protoporphyria (EPP) can readily be identified in mitogen-stimulated lymphocytes since such cells from patients with EPP...

Metabolism of estradiol in liver cell culture. Differential responses of C-2 and C-16 oxidations to drugs and other chemicals that induce selective species of cytochrome P-450.

Schneider, J, Sassa, S, Kappas, A

The oxidative metabolism of estradiol (the natural estrogen 2,3,5(10)-estratriene-3,17 beta-diol) at positions C-2 and C-16 was examined in primary cultures of chick embryo liver cells using...

Porphyrin-heme biosynthesis in organotypic cultures of mouse dorsal root ganglia. Effects of heme and lead on porphyrin synthesis and peripheral myelin.

Whetsell, W O, Sassa, S, Kappas, A

Well-myelinated cultures of mouse dorsal root ganglia incubated for 48 h with sigma-aminolevulinic acid (ALA) showed intense porphyrin fluorescence localized in myelin sheaths but not in axons or...

A Microassay for Uroporphyrinogen I Synthase, One of Three Abnormal Enzyme Activities in Acute Intermittent Porphyria, and its Application to the Study of the Genetics of this Disease*

Sassa, S., Granick, S., Bickers, D. R., Bradlow, H. L., Kappas, A.

A new spectrofluorometric assay is described for quantitating uroporphyrinogen I synthase (EC 4.3.1.8) activity in volumes of human blood as small as 2 μl. By this sensitive assay the inheritance of...

The liver excretes large amounts of heme into bile when heme oxygenase is inhibited competitively by Sn-protoporphyrin.

Kappas, A, Simionatto, C S, Drummond, G S, Sassa, S, Anderson, K E

TinIV-protoporphyrin IX (Sn-protoporphyrin) potently inhibits heme degradation to bilirubin in vitro and in vivo, and it completely suppresses neonatal hyperbilirubinemia in experimental animals,...

Control of heme metabolism with synthetic metalloporphyrins.

Kappas, A, Drummond, G S

Studies with synthetic metal-porphyrin complexes in which the central iron atom of heme is replaced by other elements indicate that those heme analogues that cannot be enzymatically degraded to bile...

Sn-protoporphyrin rapidly and markedly enhances the heme saturation of hepatic tryptophan pyrrolase. Evidence that this synthetic metalloporphyrin increases the functional content of heme in the liver.

Kappas, A, Drummond, G S, Sardana, M K

Sn-protoporphyrin is a potent competitive inhibitor of heme oxygenase, the rate-limiting enzyme in heme degradation to bile pigment, and has been successfully utilized to suppress hyperbilirubinemia...

Sn-protoporphyrin inhibition of fetal and neonatal brain heme oxygenase. Transplacental passage of the metalloporphyrin and prenatal suppression of hyperbilirubinemia in the newborn animal.

Drummond, G S, Kappas, A

Sn(tin)-protoporphyrin, a potent competitive inhibitor of heme oxygenase, can suppress hyperbilirubinemia in animal neonates and significantly reduce plasma bilirubin levels in animals and man. To...

Studies on the mechanism of Sn-protoporphyrin suppression of hyperbilirubinemia. Inhibition of heme oxidation and bilirubin production.

Simionatto, C S, Anderson, K E, Drummond, G S, Kappas, A

The synthetic heme analogue Sn-protoporphyrin is a potent competitive inhibitor of heme oxygenase, the rate-limiting enzyme in heme degradation to bile pigment, and can entirely suppress...

Sn-protoporphyrin suppresses chemically induced experimental hepatic porphyria. Potential clinical implications.

Galbraith, R A, Drummond, G S, Kappas, A

The ability of Sn(tin)-protoporphyrin to inhibit the induction of hepatic delta-aminolevulinate (ALA) synthase by allylisopropyl acetamide (AIA) was examined in the adult rat. Doses of...

Immunochemical study of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.

Fujita, H, Sassa, S, Toback, A C, Kappas, A

Hepatoerythropoietic porphyria (HEP) is due to a marked deficiency of uroporphyrinogen (URO) decarboxylase, a cytosolic enzyme in the heme biosynthetic pathway. Using a radioimmunoassay method, we...

An experimental model of postnatal jaundice in the suckling rat. Suppression of induced hyperbilirubinemia by Sn-protoporphyrin.

Drummond, G S, Kappas, A

A model of experimental postnatal hyperbilirubinemia in the rat has been developed utilizing the heme precursor delta-aminolevulinic acid (ALA) to produce jaundice during a selective time period...

Assays for Porphyrins, δ-Aminolevulinic-Acid Dehydratase, and Porphyrinogen Synthetase in Microliter Samples of Whole Blood: Applications to Metabolic Defects Involving the Heme Pathway

Granick, S., Sassa, S., Granick, J. L., Levere, R. D., Kappas, A.

Three micromethods are described for the assay of enzymes or products of the heme biosynthetic pathway in blood. A fluorometric method for the assay of protoporphyrin may be applied to the rapid...

Cobalt inhibition of synthesis and induction of delta-aminolevulinate synthase in liver.

Maines, M D, Janousĕk, V, Tomio, J M, Kappas, A

Cobalt has complex actions on the metabolism of heme in the liver. In this organ the metal potently induces heme oxygenase (EC 1.14.99.3), and decreases cellular heme and hemoprotein content. The...

Interactions between nutritional factors and drug biotransformations in man.

Alvares, A P, Anderson, K E, Conney, A H, Kappas, A

This study was undertaken to examine the influence of nutritional factors on the activity of the mixed function oxidase system in man, which is cytochrome P-450 dependent. Three normal volunteers...

Regulation of heme pathway enzymes and cellular glutathione content by metals that do not chelate with tetrapyrroles: blockade of metal effects by thiols.

Maines, M D, Kappas, A

The trace metals nickel and platinum, which are not substrates for ferrochelatase and thus do not form heme in biological systems, were found to act similaryl to cobalt, and heme itself, in...

Selenium regulation of hepatic heme metabolism: induction of delta-aminolevulinate synthase and heme oxygenase.

Maines, M D, Kappas, A

Selenium was found to be a novel regulator of cellular heme methabolism in that the element induced both the mitochondrial enzyme delta-aminolevulinate synthase [succinyl-CoA:glycine...

Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.

Ishida, N, Fujita, H, Fukuda, Y, Noguchi, T, Doss, M, Kappas, A, ...

Cloning and expression of the defective genes for delta-aminolevulinate dehydratase (ALAD) from a patient with inherited ALAD deficiency porphyria (ADP) were carried out. Cloning of cDNAs for the...

Nutrition-endocrine interactions: induction of reciprocal changes in the delta 4-5 alpha-reduction of testosterone and the cytochrome P-450-dependent oxidation of estradiol by dietary macronutrients in man.

Kappas, A, Anderson, K E, Conney, A H, Pantuck, E J, Fishman, J, Bradlow, H L

The in vivo biotransformations of drugs known to be metabolized by enzymes localized in the endoplasmic reticulum of liver can be greatly altered by diet in humans, as we have shown previously....

The role of inorganic metals and metalloporphyrins in the induction of haem oxygenase and heat-shock protein 70 in human hepatoma cells.

Mitani, K, Fujita, H, Fukuda, Y, Kappas, A, Sassa, S

The role of inorganic metals and metalloporphyrins in the induction of mRNAs for haem oxygenase and heat-shock protein 70 (hsp70), the two heat-shock proteins, was examined in human HepG2 and Hep3B...

delta-Aminolaevulinate synthase in human HepG2 hepatoma cells. Repression by haemin and induction by chemicals.

Iwasa, F, Sassa, S, Kappas, A

delta-Aminolaevulinate (ALA) synthase, the rate-limiting enzyme in haem biosynthesis in the normal liver, was examined in human HepG2 hepatoma cells. Haemin, up to 100 microM, had no effect on ALA...

The effects of acute-phase inducers and dimethyl sulphoxide on delta-aminolaevulinate synthase activity in human HepG2 hepatoma cells.

Iwasa, F, Sassa, S, Kappas, A

The effects of acute-phase inducers and dimethyl sulphoxide (Me2SO) on delta-aminolaevulinate (ALA) synthase in HepG2 cells were examined. Treatment of cells with Me2SO resulted in a significant...

Studies of the influence of chloro-substituent sites and conformational energy in polychlorinated biphenyls on uroporphyrin formation in chick-embryo liver cell cultures.

Sassa, S, Sugita, O, Ohnuma, N, Imajo, S, Okumura, T, Noguchi, T, ...

Treatment of cultured chick-embryo liver cells with polychlorinated biphenyls (PCB) results in decreased uroporphyrinogen decarboxylase activity and increased uroporphyrin accumulation. In the...

Induction of haem synthesis in Hep G2 human hepatoma cells by dimethyl sulphoxide. A transcriptionally activated event.

Galbraith, R A, Sassa, S, Kappas, A

Exposure of cultured human hepatoma cells (Hep G2) to medium containing 2% (v/v) dimethyl sulphoxide resulted in an approximate doubling in the activity of delta-aminolaevulinate dehydratase, an...

Effects of polychlorinated biphenyl compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbital and iron on hepatic uroporphyrinogen decarboxylase. Implications for the pathogenesis of porphyria.

De Verneuil, H, Sassa, S, Kappas, A

Treatment of cultured chick embryo hepatocytes with phenobarbital, polychlorinated biphenyl compounds and 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in increased delta-aminolaevulinate synthase and...

Metal induction of haem oxygenase without concurrent degradation of cytochrome P-450. Protective effects of compound SKF 525A on the haem protein.

Drummond, G S, Rosenberg, D W, Kappas, A

The induction of hepatic haem oxygenase (EC 1.14.99.3) by a series of metals, organometals and metalloporphyrins was examined in vivo in the presence of compound SKF 525A, which is known to complex...

Prolonged induction of hepatic haem oxygenase and decreases in cytochrome P-450 content by organotin compounds.

Rosenberg, D W, Drummond, G S, Cornish, H C, Kappas, A

The administration of organotin compounds to rats in single doses causes a significant and prolonged induction of haem oxygenase and a sustained decrease in haemoprotein content in the liver. The...

Metal ion interactions in the control of haem oxygenase induction in liver and kidney.

Drummond, G S, Kappas, A

Mn2+ and Zn2+ exhibit a striking ability to block the induction by Sn2+ and Ni2+ of haem oxygenase (EC 1.14.99.3) in kidney. The blocking effects of Mn2+ and Zn2+ were found to be greatest on...

Differential responses to inducers of delta-aminolaevulinate synthase and haem oxygenase during pregnancy.

Sardana, M K, Sassa, S, Kappas, A

The responses of hepatic delta-aminolaevulinate synthase and microsomal haem oxygenase to inducers were examined in pregnant rats. 2-Allyl-2-isopropylacetamide-mediated induction of...

Studies on the mechanism of induction of haem oxygenase by cobalt and other metal ions.

Maines, M D, Kappas, A

Cobalt ions (Co2+) are potent inducers of haem oxygenase in liver and inhibit microsomal drug oxidation probably by depleting microsomal haem and cytochrome P-450. Complexing of Co2+ ions with...

A heat-inducible nuclear factor that binds to the heat-shock element of the human haem oxygenase gene.

Mitani, K, Fujita, H, Sassa, S, Kappas, A

Haem oxygenase is a heat-shock protein in several rat tissues, as well as in certain human cells such as Hep3B hepatoma cells. In common with other heat-shock-protein genes, both the human and the...

Control of heme and cytochrome P-450 metabolism by inorganic metals, organometals and synthetic metalloporphyrins.

Kappas, A, Drummond, G S

The heme-cytochrome P-450 complexes represent sensitive metabolic systems for examining the biological impact of metals on important cellular functions. Many metals, both in the inorganic form and...

Diagnosis of pseudomembranous colitis.

Kappas, A, Shinagawa, N, Arabi, Y, Thompson, H, Burdon, D, Dimock, F, ...

Twenty-eight patients with histologically proved pseudomembranous colitis have been seen in one hospital since July 1975. All patients with the disease had received antibiotics, six for infections...

Transfection of the human heme oxygenase gene into rabbit coronary microvessel endothelial cells: protective effect against heme and hemoglobin toxicity.

Abraham, N G, Lavrovsky, Y, Schwartzman, M L, Stoltz, R A, Levere, R D, Gerritsen, M E, ...

Heme oxygenase (HO) is a stress protein and has been suggested to participate in defense mechanisms against agents that may induce oxidative injury such as metals, endotoxin, heme/hemoglobin, and...

Identification of binding sites for transcription factors NF-kappa B and AP-2 in the promoter region of the human heme oxygenase 1 gene.

Lavrovsky, Y, Schwartzman, M L, Levere, R D, Kappas, A, Abraham, N G

Heme oxygenase (HO) is the rate-limiting enzyme in heme catabolism and its activity is induced by many agents, including its substrate heme, heavy metals, UV radiation, and other injurious oxidant...

The molecular defect of ferrochelatase in a patient with erythropoietic protoporphyria.

Nakahashi, Y, Fujita, H, Taketani, S, Ishida, N, Kappas, A, Sassa, S

The molecular basis of an inherited defect of ferrochelatase in a patient with erythropoietic protoporphyria (EPP) was investigated. Ferrochelatase is the terminal enzyme in the heme biosynthetic...

Heme inhibits human immunodeficiency virus 1 replication in cell cultures and enhances the antiviral effect of zidovudine.

Levere, R D, Gong, Y F, Kappas, A, Bucher, D J, Wormser, G P, Abraham, N G

The effects of heme alone and heme administered together with 3'-azido-3'-deoxythymidine (AZT) on human immunodeficiency virus replication in human peripheral blood lymphocytes and in the H9 cell...

Interference of Griseofulvin with the Segregation of Chromosomes at Mitosis in Diploid Aspergillus nidulans

Kappas, A., Georgopoulos, S. G.

Low concentrations of the antibiotic griseofulvin were found to cause increased frequencies of somatic segregation due to chromosome nondisjunction in a diploid strain of Aspergillus nidulans.

Regulation of food intake and body weight by cobalt porphyrins in animals.

Galbraith, R A, Kappas, A

Cobalt-substituted protoporphyrin administered subcutaneously to normal adult rats elicited prompt decreases in food intake and sustained decreases in body weight. Repetitive parenteral...

Dual control mechanism for heme oxygenase: tin(IV)-protoporphyrin potently inhibits enzyme activity while markedly increasing content of enzyme protein in liver.

Sardana, M K, Kappas, A

Tin(IV)-protoporphyrin (Sn-protoporphyrin) potently inhibits heme degradation to bile pigments in vitro and in vivo, a property that confers upon this synthetic compound the ability to suppress a...

Induction of a deficiency of steroid delta 4-5 alpha-reductase activity in liver by a porphyrinogenic drug.

Kappas, A, Bradlow, H L, Bickers, D R, Alvares, A P

The hepatic enzymes that catalyze drug oxidations and the reductive metabolism of steroid hormones to 5alpha-derivatives are localized in membranes of the endoplasmic reticulum. Phenobarbital, which...

The cytochrome P-450-depleted animal: an experimental model for in vivo studies in chemical biology.

Drummond, G S, Kappas, A

An experimental method is described to deplete markedly in vivo the cytochrome P-450 content of liver for prolonged periods of time. The method uses the synthetic metalloporphyrin cobalt-heme (cobalt...

Thyroid hormone regulation of heme oxidation in the liver.

Smith, T J, Drummond, G S, Kourides, I A, Kappas, A

The effects of 3,5,3'-triiodothyronine (T3) on heme oxygenase (EC 1.14.99.3) activity and cytochrome P-450 content in liver were examined in thyroidectomized rats. T3, when administered for 5 days at...

Prevention of neonatal hyperbilirubinemia by tin protoporphyrin IX, a potent competitive inhibitor of heme oxidation.

Drummond, G S, Kappas, A

The effects of various metalloporphyrins on hepatic heme oxygenase (EC 1.14.99.3) activity were examined in order to identify compounds that could inhibit heme degradation to bile pigment and might...

Radiometric analysis of biological oxidations in man: sex differences in estradiol metabolism.

Fishman, J, Bradlow, H L, Schneider, J, Anderson, K E, Kappas, A

The oxidative metabolism of estradiol was studied in normal men and women by a radiometric procedure that provides information on the totality of the biotransformations concerned. The release of 3H...

Studies in porphyria: functional evidence for a partial deficiency of ferrochelatase activity in mitogen-stimulated lymphocytes from patients with erythropoietic protoporphyria.

Sassa, S, Zalar, G L, Poh-Fitzpatrick, M B, Anderson, K E, Kappas, A

In this paper we show that the ferrochelatase defect in erythropoietic protoporphyria (EPP) can readily be identified in mitogen-stimulated lymphocytes since such cells from patients with EPP...

Metabolism of estradiol in liver cell culture. Differential responses of C-2 and C-16 oxidations to drugs and other chemicals that induce selective species of cytochrome P-450.

Schneider, J, Sassa, S, Kappas, A

The oxidative metabolism of estradiol (the natural estrogen 2,3,5(10)-estratriene-3,17 beta-diol) at positions C-2 and C-16 was examined in primary cultures of chick embryo liver cells using...

Porphyrin-heme biosynthesis in organotypic cultures of mouse dorsal root ganglia. Effects of heme and lead on porphyrin synthesis and peripheral myelin.

Whetsell, W O, Sassa, S, Kappas, A

Well-myelinated cultures of mouse dorsal root ganglia incubated for 48 h with sigma-aminolevulinic acid (ALA) showed intense porphyrin fluorescence localized in myelin sheaths but not in axons or...

A Microassay for Uroporphyrinogen I Synthase, One of Three Abnormal Enzyme Activities in Acute Intermittent Porphyria, and its Application to the Study of the Genetics of this Disease*

Sassa, S., Granick, S., Bickers, D. R., Bradlow, H. L., Kappas, A.

A new spectrofluorometric assay is described for quantitating uroporphyrinogen I synthase (EC 4.3.1.8) activity in volumes of human blood as small as 2 μl. By this sensitive assay the inheritance of...

The liver excretes large amounts of heme into bile when heme oxygenase is inhibited competitively by Sn-protoporphyrin.

Kappas, A, Simionatto, C S, Drummond, G S, Sassa, S, Anderson, K E

TinIV-protoporphyrin IX (Sn-protoporphyrin) potently inhibits heme degradation to bilirubin in vitro and in vivo, and it completely suppresses neonatal hyperbilirubinemia in experimental animals,...

Control of heme metabolism with synthetic metalloporphyrins.

Kappas, A, Drummond, G S

Studies with synthetic metal-porphyrin complexes in which the central iron atom of heme is replaced by other elements indicate that those heme analogues that cannot be enzymatically degraded to bile...

Sn-protoporphyrin rapidly and markedly enhances the heme saturation of hepatic tryptophan pyrrolase. Evidence that this synthetic metalloporphyrin increases the functional content of heme in the liver.

Kappas, A, Drummond, G S, Sardana, M K

Sn-protoporphyrin is a potent competitive inhibitor of heme oxygenase, the rate-limiting enzyme in heme degradation to bile pigment, and has been successfully utilized to suppress hyperbilirubinemia...

Sn-protoporphyrin inhibition of fetal and neonatal brain heme oxygenase. Transplacental passage of the metalloporphyrin and prenatal suppression of hyperbilirubinemia in the newborn animal.

Drummond, G S, Kappas, A

Sn(tin)-protoporphyrin, a potent competitive inhibitor of heme oxygenase, can suppress hyperbilirubinemia in animal neonates and significantly reduce plasma bilirubin levels in animals and man. To...

Studies on the mechanism of Sn-protoporphyrin suppression of hyperbilirubinemia. Inhibition of heme oxidation and bilirubin production.

Simionatto, C S, Anderson, K E, Drummond, G S, Kappas, A

The synthetic heme analogue Sn-protoporphyrin is a potent competitive inhibitor of heme oxygenase, the rate-limiting enzyme in heme degradation to bile pigment, and can entirely suppress...

Sn-protoporphyrin suppresses chemically induced experimental hepatic porphyria. Potential clinical implications.

Galbraith, R A, Drummond, G S, Kappas, A

The ability of Sn(tin)-protoporphyrin to inhibit the induction of hepatic delta-aminolevulinate (ALA) synthase by allylisopropyl acetamide (AIA) was examined in the adult rat. Doses of...

Immunochemical study of uroporphyrinogen decarboxylase in a patient with mild hepatoerythropoietic porphyria.

Fujita, H, Sassa, S, Toback, A C, Kappas, A

Hepatoerythropoietic porphyria (HEP) is due to a marked deficiency of uroporphyrinogen (URO) decarboxylase, a cytosolic enzyme in the heme biosynthetic pathway. Using a radioimmunoassay method, we...

An experimental model of postnatal jaundice in the suckling rat. Suppression of induced hyperbilirubinemia by Sn-protoporphyrin.

Drummond, G S, Kappas, A

A model of experimental postnatal hyperbilirubinemia in the rat has been developed utilizing the heme precursor delta-aminolevulinic acid (ALA) to produce jaundice during a selective time period...

Assays for Porphyrins, δ-Aminolevulinic-Acid Dehydratase, and Porphyrinogen Synthetase in Microliter Samples of Whole Blood: Applications to Metabolic Defects Involving the Heme Pathway

Granick, S., Sassa, S., Granick, J. L., Levere, R. D., Kappas, A.

Three micromethods are described for the assay of enzymes or products of the heme biosynthetic pathway in blood. A fluorometric method for the assay of protoporphyrin may be applied to the rapid...

Cobalt inhibition of synthesis and induction of delta-aminolevulinate synthase in liver.

Maines, M D, Janousĕk, V, Tomio, J M, Kappas, A

Cobalt has complex actions on the metabolism of heme in the liver. In this organ the metal potently induces heme oxygenase (EC 1.14.99.3), and decreases cellular heme and hemoprotein content. The...

Interactions between nutritional factors and drug biotransformations in man.

Alvares, A P, Anderson, K E, Conney, A H, Kappas, A

This study was undertaken to examine the influence of nutritional factors on the activity of the mixed function oxidase system in man, which is cytochrome P-450 dependent. Three normal volunteers...

Regulation of heme pathway enzymes and cellular glutathione content by metals that do not chelate with tetrapyrroles: blockade of metal effects by thiols.

Maines, M D, Kappas, A

The trace metals nickel and platinum, which are not substrates for ferrochelatase and thus do not form heme in biological systems, were found to act similaryl to cobalt, and heme itself, in...

Selenium regulation of hepatic heme metabolism: induction of delta-aminolevulinate synthase and heme oxygenase.

Maines, M D, Kappas, A

Selenium was found to be a novel regulator of cellular heme methabolism in that the element induced both the mitochondrial enzyme delta-aminolevulinate synthase [succinyl-CoA:glycine...

Cloning and expression of the defective genes from a patient with delta-aminolevulinate dehydratase porphyria.

Ishida, N, Fujita, H, Fukuda, Y, Noguchi, T, Doss, M, Kappas, A, ...

Cloning and expression of the defective genes for delta-aminolevulinate dehydratase (ALAD) from a patient with inherited ALAD deficiency porphyria (ADP) were carried out. Cloning of cDNAs for the...

Nutrition-endocrine interactions: induction of reciprocal changes in the delta 4-5 alpha-reduction of testosterone and the cytochrome P-450-dependent oxidation of estradiol by dietary macronutrients in man.

Kappas, A, Anderson, K E, Conney, A H, Pantuck, E J, Fishman, J, Bradlow, H L

The in vivo biotransformations of drugs known to be metabolized by enzymes localized in the endoplasmic reticulum of liver can be greatly altered by diet in humans, as we have shown previously....

The role of inorganic metals and metalloporphyrins in the induction of haem oxygenase and heat-shock protein 70 in human hepatoma cells.

Mitani, K, Fujita, H, Fukuda, Y, Kappas, A, Sassa, S

The role of inorganic metals and metalloporphyrins in the induction of mRNAs for haem oxygenase and heat-shock protein 70 (hsp70), the two heat-shock proteins, was examined in human HepG2 and Hep3B...

delta-Aminolaevulinate synthase in human HepG2 hepatoma cells. Repression by haemin and induction by chemicals.

Iwasa, F, Sassa, S, Kappas, A

delta-Aminolaevulinate (ALA) synthase, the rate-limiting enzyme in haem biosynthesis in the normal liver, was examined in human HepG2 hepatoma cells. Haemin, up to 100 microM, had no effect on ALA...

The effects of acute-phase inducers and dimethyl sulphoxide on delta-aminolaevulinate synthase activity in human HepG2 hepatoma cells.

Iwasa, F, Sassa, S, Kappas, A

The effects of acute-phase inducers and dimethyl sulphoxide (Me2SO) on delta-aminolaevulinate (ALA) synthase in HepG2 cells were examined. Treatment of cells with Me2SO resulted in a significant...

Studies of the influence of chloro-substituent sites and conformational energy in polychlorinated biphenyls on uroporphyrin formation in chick-embryo liver cell cultures.

Sassa, S, Sugita, O, Ohnuma, N, Imajo, S, Okumura, T, Noguchi, T, ...

Treatment of cultured chick-embryo liver cells with polychlorinated biphenyls (PCB) results in decreased uroporphyrinogen decarboxylase activity and increased uroporphyrin accumulation. In the...

Induction of haem synthesis in Hep G2 human hepatoma cells by dimethyl sulphoxide. A transcriptionally activated event.

Galbraith, R A, Sassa, S, Kappas, A

Exposure of cultured human hepatoma cells (Hep G2) to medium containing 2% (v/v) dimethyl sulphoxide resulted in an approximate doubling in the activity of delta-aminolaevulinate dehydratase, an...

A heat-inducible nuclear factor that binds to the heat-shock element of the human haem oxygenase gene.

Mitani, K, Fujita, H, Sassa, S, Kappas, A

Haem oxygenase is a heat-shock protein in several rat tissues, as well as in certain human cells such as Hep3B hepatoma cells. In common with other heat-shock-protein genes, both the human and the...

Effects of polychlorinated biphenyl compounds, 2,3,7,8-tetrachlorodibenzo-p-dioxin, phenobarbital and iron on hepatic uroporphyrinogen decarboxylase. Implications for the pathogenesis of porphyria.

De Verneuil, H, Sassa, S, Kappas, A

Treatment of cultured chick embryo hepatocytes with phenobarbital, polychlorinated biphenyl compounds and 2,3,7,8-tetrachlorodibenzo-p-dioxin resulted in increased delta-aminolaevulinate synthase and...

Metal induction of haem oxygenase without concurrent degradation of cytochrome P-450. Protective effects of compound SKF 525A on the haem protein.

Drummond, G S, Rosenberg, D W, Kappas, A

The induction of hepatic haem oxygenase (EC 1.14.99.3) by a series of metals, organometals and metalloporphyrins was examined in vivo in the presence of compound SKF 525A, which is known to complex...

Prolonged induction of hepatic haem oxygenase and decreases in cytochrome P-450 content by organotin compounds.

Rosenberg, D W, Drummond, G S, Cornish, H C, Kappas, A

The administration of organotin compounds to rats in single doses causes a significant and prolonged induction of haem oxygenase and a sustained decrease in haemoprotein content in the liver. The...

Metal ion interactions in the control of haem oxygenase induction in liver and kidney.

Drummond, G S, Kappas, A

Mn2+ and Zn2+ exhibit a striking ability to block the induction by Sn2+ and Ni2+ of haem oxygenase (EC 1.14.99.3) in kidney. The blocking effects of Mn2+ and Zn2+ were found to be greatest on...

Differential responses to inducers of delta-aminolaevulinate synthase and haem oxygenase during pregnancy.

Sardana, M K, Sassa, S, Kappas, A

The responses of hepatic delta-aminolaevulinate synthase and microsomal haem oxygenase to inducers were examined in pregnant rats. 2-Allyl-2-isopropylacetamide-mediated induction of...

Studies on the mechanism of induction of haem oxygenase by cobalt and other metal ions.

Maines, M D, Kappas, A

Cobalt ions (Co2+) are potent inducers of haem oxygenase in liver and inhibit microsomal drug oxidation probably by depleting microsomal haem and cytochrome P-450. Complexing of Co2+ ions with...

Control of heme and cytochrome P-450 metabolism by inorganic metals, organometals and synthetic metalloporphyrins.

Kappas, A, Drummond, G S

The heme-cytochrome P-450 complexes represent sensitive metabolic systems for examining the biological impact of metals on important cellular functions. Many metals, both in the inorganic form and...

Diagnosis of pseudomembranous colitis.

Kappas, A, Shinagawa, N, Arabi, Y, Thompson, H, Burdon, D, Dimock, F, ...

Twenty-eight patients with histologically proved pseudomembranous colitis have been seen in one hospital since July 1975. All patients with the disease had received antibiotics, six for infections...

Studies with the haeme oxygenase inhibitor Sn-protoporphyrin in patients with primary biliary cirrhosis and idiopathic haemochromatosis.

Berglund, L, Angelin, B, Hultcrantz, R, Einarsson, K, Emtestam, L, Drummond, G, ...

Sn(tin4+)-protoporphyrin, a potent competitive inhibitor of haeme oxygenase, the rate limiting enzyme in the degradation of haeme to bile pigments, was given intravenously to six patients with...

Heterotopic gastric mucosa together with intestinal metaplasia and moderate dysplasia in the gall bladder: report of two clinically unusual cases with literature review

Xeropotamos, N, Skopelitou, A, Batsis, C., Kappas, A

We report the clinicopathological findings of two patients with ectopic gastric mucosa within the gall ladder. The first patient, a 78 year old man, was asymptomatic. He was admitted to hospital for...

Enzymes of heme metabolism is the kidney. Regulation by trace metals which do not form heme complexes

Maines, MD, Kappas, A

The in vivo regulation by metal ions of the enzymes of heme metabolism in kidney-particularly of ALAS, the rate-limiting enzyme in heine formation- was investigated. Ni(2+) and Pt(4+), metals which...

Potent heme-degrading action of antimony and antimony-containing parasiticidal agents

Drummond, GS, Kappas, A

The ability of antimony and antimony-containing parasiticidal agents to enhance the rate of heme degradation in liver and kidney was investigated. Trivalent antimony was shown to be an extremely...

PLASMA MEMBRANES OF THE RAT LIVER : Isolation and Enzymatic Characterization of a Fraction Rich in Bile Canaliculi

Song, C. S., Rubin, W., Rifkind, A. B., Kappas, A.

A method is described for the rapid isolation of a plasma membrane fraction containing a high concentration of intact bile canaliculi from the rat liver. Isolated bile canaliculi retain most of the...

Sideroblastic anaemia associated with lincomycin therapy.

Kokkini, G., Tsianos, E., Kappas, A.

Sideroblastic anaemia developed after lincomycin therapy in a 58-year-old woman. The anaemia proved completely reversible after termination of lincomycin therapy and the introduction of pyridoxine....