17 results on '"Annella, T"'
Search Results
2. Presence of CuZnsuperoxide dismutase in human serum lipoproteins
- Author
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MONDOLA, PAOLO, BIFULCO M., SERU\' R., ANNELLA T., CIRIOLO M. R., SANTILLO, MARIAROSARIA, Mondola, Paolo, Bifulco, M., Seru\', R., Annella, T., Ciriolo, M. R., and Santillo, Mariarosaria
- Published
- 2000
3. EVIDENCE FOR SECRETION OF CYTOSOLIC CuZnSOD BY HEPG2 CELLS AND HUMAN FIBROBLASTS
- Author
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MONDOLA, PAOLO, ANNELLA T., SANTILLO, MARIAROSARIA, SANTANGELO F., Mondola, Paolo, Annella, T., Santillo, Mariarosaria, and Santangelo, F.
- Published
- 1996
4. Hepatitis B virus DNA in chronic HBsAg carriers: correlation with HBeAg/anti-HBe status, anti-HD and liver histology
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Stroffolini T, Evangelista Sagnelli, Rapicetta M, Fm, Felaco, Filippini P, Annella T, Petruzziello A, Chionne P, Sarrecchia B, Piccinino F, Stroffolini, T, Sagnelli, E, Rapicetta, M, Felaco, Fm, Filippini, Pietro, Annella, T, Petruzziello, A, Chionne, P, Sarrecchia, B, and Piccinino, F.
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Adult ,Male ,Hepatitis B virus ,Hepatitis B Surface Antigens ,Adolescent ,Radioimmunoassay ,Nucleic Acid Hybridization ,Middle Aged ,Hepatitis B ,Liver ,Child, Preschool ,Carrier State ,Chronic Disease ,DNA, Viral ,Humans ,Female ,Hepatitis Antibodies ,Hepatitis B e Antigens ,Hepatitis Delta Virus ,Child - Abstract
Hepatitis B virus DNA was determined in the sera of 198 chronic hepatitis B surface antigen (HBsAg) carriers by the spot hybridization technique. The results were correlated with hepatitis Be antigen (HBeAg) and antibody (anti-HBe), delta antibody (anti-HD) and liver histology. All subjects had a liver biopsy. The prevalence of HBV DNA was 63% in HBeAg-positive subjects and 8.8% in anti-HBe positives. HBV DNA was not found more frequently in chronic HBsAg carriers who had histological evidence of liver disease than in carriers without such evidence. Anti-HD was detected in 48.5% of subjects, with an increasing trend (p less than 0.001) according to the severity of liver disease. Among patients with more severe liver disease (CAH and cirrhosis), HBV DNA and HBeAg were detected less frequently in anti-HD-positive than in anti-HD-negative subjects (7% vs. 42.3%, p less than 0.001 and 7% vs. 34.4%, p less than 0.005, respectively). These findings indicate that HDV infection jointly affects both HBeAg status and HBV DNA.
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- 1992
5. Opposite functions of Ki and Ha ras genes in the regulation of redox signals
- Author
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Santillo, M, Mondola, P, Ser, R, Annella, T, Cassano, S, Ciullo, I, Tecce, Mario Felice, Iacomino, G, Damiano, S, Cuda, G, Patern, R, Martignetti, V, Mele, E, Feliciello, A, and Avvedimento, E. V.
- Published
- 2001
6. Hepatitis B virus DNA in chronic HBsAg carriers: Correlation with HBeAg/Anti-HBe status, Anti-HD and liver histology
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Stroffolini, T., Sagnelli, E., Rapicetta, M., Felaco, F. M., Pietro Filippini, Annella, T., Petruzziello, A., Chionne, P., Sarrecchia, B., Piccinino, F., and Giusti, G.
7. Free fatty acids modulate LDL receptor activity in BHK-21 cells
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Maurizio Bifulco, Daniela Lattero, Paolo Mondola, Rosalba Vitelli, Tiziana Annella, Rosalba Serù, Cecilia Bucci, Mariarosaria Santillo, Bucci, Cecilia, Serù, R, Annella, T, Vitelli, R, Lattero, D, Bifulco, M, Mondola, P, Santillo, M., Bucci, C., Seru, R., Annella, T., Vitelli, R., Lattero, D., Bifulco, M., Mondola, Paolo, and Santillo, Mariarosaria
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medicine.medical_specialty ,Linoleic acid ,Blotting, Western ,Biology ,Fatty Acids, Nonesterified ,Kidney ,Cell Line ,Fatty Acids, Monounsaturated ,chemistry.chemical_compound ,Internal medicine ,Cricetinae ,medicine ,Animals ,Lovastatin ,Cells, Cultured ,chemistry.chemical_classification ,L-Lactate Dehydrogenase ,Fatty acid ,Fibroblasts ,Elaidic acid ,Hydroxycholesterols ,Oleic acid ,Endocrinology ,chemistry ,Biochemistry ,Receptors, LDL ,LDL receptor ,Free fatty acid receptor ,Fatty Acids, Unsaturated ,Arachidonic acid ,lipids (amino acids, peptides, and proteins) ,Hydroxymethylglutaryl-CoA Reductase Inhibitors ,Cardiology and Cardiovascular Medicine ,Polyunsaturated fatty acid - Abstract
It has been shown that dietary fatty acids affect serum low density lipoprotein (LDL) levels, but the mechanism responsible for this effect is still under debate. Here we investigate the effect of different free fatty acids on LDL receptor activity in BHK-21 cells. These cells possess a classical LDL receptor strongly regulated by substances like 25-OH-cholesterol or lovastatin. Preincubation of cells for 24 h with both oleic (cis 18:1) and its trans counterpart, elaidic acid, enhanced I-125-LDL binding, internalization and degradation, being oleic acid more effective than elaidic acid. Among polyunsaturated fatty acids (PUFA) of the n-6 series arachidonic acid (20:4) enhanced LDL receptor activity more than linoleic acid (18:2), and among PUFA of the n-3 series docosahexaenoic (22:6) and eicosapentaenoic acids (20:5) were more effective compared to a-linolenic acid (18:3). Conversely, preincubation of cells with saturated fatty acids, palmitic (16:0) and stearic (18:0) acids, decreased binding, internalization and degradation of I-125-LDL. Scatchard analysis of binding data obtained with palmitic and oleic acids showed that these two fatty acids affect LDL receptor number without altering receptor affinity. The regulatory effect of free fatty acids on LDL receptor activity in BHK-21 cells is consistent with the hypothesis that the ability of fatty acids to modulate LDL-cholesterol levels in vivo is mediated, at least in part, by an action on receptor-dependent uptake of LDL. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.
- Published
- 1998
8. ANIMAL-MODELS FOR LYSOSOMAL STORAGE DISEASES - A NEW CASE OF FELINE MUCOPOLYSACCHARIDOSIS-VI
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G. Spagnuolo, R. Cerundolo, Tiziana Annella, Aurora Daniele, Angelo Elio Gravino, P. Di Natale, D. de Caprariis, DI NATALE, P, Annella, T, Daniele, Aurora, Spagnuolo, G, Cerundolo, R, DE CAPRARIIS, D, Gravino, Ae, DI NATALE, P., Annella, T., Daniele, A., Spagnuolo, G., Gravino, ANGELO ELIO, Cerundolo, R., DE CAPRARIIS, D., Natale, P. D., and Caprariis, D. d.
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medicine.medical_specialty ,Pathology ,Mucopolysaccharidosis I ,Mucopolysaccharidosis ,Urine ,Biology ,Bone and Bones ,Glycosaminoglycan ,Animal, Female, Glycosaminoglycan ,Chondro-4-Sulfatase ,Internal medicine ,Genetics ,Paralysis ,medicine ,Lysosomal storage disease ,Animals ,Humans ,Genetics (clinical) ,Glycosaminoglycans ,Animals, Bone and Bone ,CATS ,pathology/urine/veterinary ,Mucopolysaccharidosis VI ,medicine.disease ,Disease Models, Animal ,Endocrinology ,urine, Humans, Mucopolysaccharidosis I ,Cats ,Female ,abnormalities, Cats, Chondro-4-Sulfatase ,medicine.symptom ,deficiency/genetics, Disease Model ,Intracellular - Abstract
Two long-haired Siamese cats are reported with clinical manifestations of human mucopolysaccharidosis VI (Maroteaux-Lamy disease): facial dysmorphia, dysostosis multiplex, paralysis. Urine of the two affected animals contained a high concentration of glycosaminoglycans, as detected by the dimethylmethylene blue test. Qualitative analysis, performed by thin-layer chromatography of the cetylpyridinium chloride-precipitable material, showed dermatan sulphate. Excessive incorporation of [35S]sulphate in the intracellular mucopolysaccharide of cultured fibroblasts and deficiency of arylsulphatase B in such cells indicate that these cats are affected by Maroteaux-Lamy disease. They should thus be considered the first European case of feline mucopolysaccharidosis VI. © 1992 SSIEM and Kluwer Academic Publishers.
- Published
- 1992
9. Presence of CuZn superoxide dismutase in human serum lipoproteins
- Author
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Mariarosaria Santillo, Maurizio Bifulco, Rosalba Serù, Maria Rosa Ciriolo, Paolo Mondola, Tiziana Annella, Mondola, Paolo, Bifulco, M., Serù, R., Annella, T., Ciriolo, M. R., and Santillo, Mariarosaria
- Subjects
Adult ,Male ,Lipoproteins ,Blotting, Western ,Biophysics ,Blood lipids ,Enzyme-Linked Immunosorbent Assay ,Biochemistry ,Superoxide dismutase ,chemistry.chemical_compound ,Structural Biology ,Genetics ,Humans ,Bovine serum albumin ,Lipoprotein ,Xanthine oxidase ,Molecular Biology ,biology ,Superoxide Dismutase ,Cholesterol ,Biological Transport ,CuZn-superoxide dismutase ,Cell Biology ,Middle Aged ,Xanthine ,Molecular biology ,Lipoproteins, LDL ,Biophysic ,chemistry ,biology.protein ,Emulsions ,Female ,lipids (amino acids, peptides, and proteins) ,Dismutase ,Carrier Proteins ,Lipoproteins, HDL ,Ultracentrifugation ,Protein Binding - Abstract
It has previously been demonstrated that CuZn-superoxide dismutase (SOD) is secreted by several human cell lines. This suggests that the circulating enzyme derives from both hemolysis and peripheral tissues as a result of cellular secretion. In the present report, we evaluated the presence of CuZn-SOD in human serum lipoproteins by both enzyme-linked immunosorbent assay and Western blot analysis of immunoprecipitated lipoprotein samples. The distribution of CuZn-SOD activity among the different lipoprotein fractions was also determined by the xanthine/xanthine oxidase method. The results demonstrated that CuZn-SOD is noticeably present in serum lipoproteins and mainly in low and high density lipoproteins (LDL and HDL). Moreover, experiments performed by incubating CuZn-SOD with a lipid emulsion and subsequent separation of the lipid fraction by ultracentrifugation showed that this enzyme associates in a saturable manner with lipids. The CuZn-SOD bound to LDL and HDL could exert a physiological protective role against oxidative damage of these lipoprotein classes that carry out a crucial role in the cholesterol transport.
- Published
- 2000
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10. Inhibitors of Ras Farnesylation Revert the Increased Resistance to Oxidative Stress in K-rasTransformed NIH 3T3 Cells
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Mariarosaria Santillo, Tiziana Annella, Rosalba Serù, Mario Vitale, S. Iossa, Paolo Mondola, Maurizio Bifulco, Anna Gioielli, Santillo, Mariarosaria, Mondola, Paolo, Gioielli, A., Seru, R., Iossa, S., Annella, T., Vitale, M., Bifulco, M., Serù, R., and Vitale, Mario
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Mutant ,Organophosphonates ,Protein Prenylation ,Biophysics ,Cancer therapy ,Antineoplastic Agents ,medicine.disease_cause ,Biochemistry ,3T3 cells ,Mice ,Prenylation ,medicine ,Animals ,Lovastatin ,Molecular Biology ,chemistry.chemical_classification ,Reactive oxygen species ,Lipid peroxide ,Chemistry ,3T3 Cells ,Cell Biology ,Molecular biology ,Oxidative Stress ,Cell Transformation, Neoplastic ,Genes, ras ,medicine.anatomical_structure ,lipids (amino acids, peptides, and proteins) ,Oxidative stress ,medicine.drug - Abstract
Tumor resistance to oxidative stress prevents the efficacy of cancer therapy based upon a free radical-mediated mechanism. K-ras transformed NIH 3T3 cells (E32-4-2) showed, under oxidative stress, reactive oxygen species (ROS) levels 10-fold lower and lipid peroxide levels 56% lower, compared to their nontransformed counterpart. Since p21(ras) activity depends upon farnesylation, we tested the effect of the inhibitors of farnesylation lovastatin and (alpha-hydroxyfarnesyl) phosphonic acid on susceptibility to oxidative stress in these cells. Preincubation of cells for 24 h with 10 mu M lovastatin resulted in a 10-fold increase of ROS levels and a 50% increase of lipid peroxide levels measured under pro-oxidant conditions. Similarly, preincubation of cells with 100 mu M (alpha-hydroxyfarnesyl) phosphonic acid fur 24 h enhanced stress-induced levels of either ROS (7.5-fold) or lipid peroxides (33%). The effect of lovastatin and (alpha-hydroxyfarnesyl) phosphonic acid is specifically due to their ability to inhibit p21(ras) activity. In fact, inhibition of p21(ras) by transfecting E32-4-2 cells with the transdominant negative mutant of H-ras (L61,S186) led, analogously to lovastatin or (alpha-hydroxyfarnesyl) phosphonic acid treatment, to a strong increase of stress-induced ROS levels. These results suggest that farnesylation inhibitors could be used as an adjuvant therapy to improve the tumoricidal effect of cancer treatment based upon free-radical production in ms-dependent tumors. (C) 1996 Academic Press
- Published
- 1996
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11. Biochemical diagnosis of mucopolysaccharidoses: Experience of 297 diagnoses in a 15-year period (1977–1991)
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Rita Pallini, Tiziana Annella, T De Luca, G. Spagnuolo, P. Rosario, E. Morabito, Aurora Daniele, P. Di Natale, DI NATALE, P, Annella, T, Daniele, Aurora, DE LUCA, T, Morabito, E, Pallini, R, Rosario, P, and Spagnuolo, G.
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Adult ,Heterozygote ,medicine.medical_specialty ,Pathology ,Adolescent ,Period (gene) ,Mucopolysaccharidosis ,Reference Values ,Internal medicine ,Genotype ,Genetics ,Humans ,Medicine ,Lymphocytes ,Medical diagnosis ,Child ,Gene ,Genetics (clinical) ,business.industry ,Homozygote ,Infant ,Heterozygote advantage ,Fibroblasts ,Mucopolysaccharidoses ,medicine.disease ,Human genetics ,Enzymes ,genomic DNA ,Italy ,Child, Preschool ,Lysosomes ,business - Abstract
We report the results over 15 years (1977-1991) for biochemical diagnoses of patients referred from throughout Italy and suspected of having a mucopolysaccharidosis. Of these, 147 patients were diagnosed as being homozygous or hemizygous for a specific lysosomal enzyme deficiency; 74 pregnancies at risk were monitored in their families; 76 heterozygote diagnoses were performed on their relatives, with a total of 48 positive diagnoses. We also report the analysis of genomic DNA from 11 unrelated Italian Hunter patients, using pc2S15 probe. DNA from two patients, digested with Pst-I, showed a variant pattern of hybridization caused by deletion or rearrangement of the gene. © 1993 Society for the Study of Inborn Errors of Metabolism and Kluwer Academic Publishers.
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- 1993
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12. SECRETION AND INCREASE OF INTRACELLULAR CuZn SUPEROXIDE DISMUTASE CONTENT IN HUMAN NEUROBLASTOMA SK-N-BE CELLS SUBJECTED TO OXIDATIVE STRESS
- Author
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Mariarosaria Santillo, Tiziana Annella, Anna Gioielli, S. Iossa, Rosalba Serù, Paolo Mondola, Santangelo F, Mondola, P., Annella, T., Seru', R., Iossa, S., and Santillo, M.
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Free Radicals ,Ascorbic Acid ,medicine.disease_cause ,Thiobarbituric Acid Reactive Substances ,Superoxide dismutase ,Neuroblastoma ,chemistry.chemical_compound ,Western blot ,Malondialdehyde ,Tumor Cells, Cultured ,medicine ,Humans ,Secretion ,Ferrous Compounds ,L-Lactate Dehydrogenase ,biology ,medicine.diagnostic_test ,Superoxide Dismutase ,Chemistry ,General Neuroscience ,Ascorbic acid ,Molecular biology ,Kinetics ,Oxidative Stress ,Cell culture ,biology.protein ,Intracellular ,Oxidative stress - Abstract
CuZn superoxide dismutase (SOD) secretion was detected in media of [S-35]cysteine-labeled human neuroblastoma SK-N-BE cells precipitated with antihuman CuZn SOD antibodies. The ability of Fe2+/ascorbate oxidative stress to induce CuZn SOD in SK-N-BE cells was evaluated by Western blot analysis. The results showed that, like human hepatocarcinoma cells and human fibroblasts, SK-N-BE cells secrete CuZn SOD. In addition, the CuZn SOD concentration was higher in cells subjected to oxidative stress than in unstressed cells. The secretion of CuZn SOD and the ability of Fe2+/ascorbate to increase its protein content in SK-N-BE cells indicates that this enzyme protects the brain from damage induced by oxidative stress. (C) 1998 Elsevier Science Inc.
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- 1998
13. Heterogeneity of DNA and RNA in Hunter patients
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Tiziana Annella, Aurora Daniele, P. Di Natale, Annella, T, Daniele, Aurora, and DI NATALE, P.
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Iduronate Sulfatase ,Biology ,Genetics ,medicine ,Humans ,Northern blot ,Lymphocytes ,Gene ,Genetics (clinical) ,Southern blot ,Mucopolysaccharidosis II ,Chromosome Aberrations ,Gene Rearrangement ,RNA ,Hunter syndrome ,Gene rearrangement ,DNA ,medicine.disease ,Blotting, Northern ,Molecular biology ,Blot ,genomic DNA ,Blotting, Southern ,Chromosome Deletion - Abstract
Genomic DNA and total RNA from lymphoblasts of nine unrelated Italian patients affected with Hunter syndrome were analyzed using a human cDNA clone coding for the lysosomal enzyme iduronate-2-sulphatase (IDS). Southern blot analysis resulted in patterns similar to the normal control for seven of the patients analyzed; an aberrant pattern was observed in two patients (F.N. and P.D.), suggesting deletions/rearrangement in the IDS gene. Northern blot analysis showed in seven patients, a pattern similar to the normal control; for patients F.N. and P.D. the pattern was atypical, i.e., normal RNA species were absent whereas two different transcripts occurred. These data confirm the heterogeneity of the molecular defects causing Hunter disease. © 1993 Springer-Verlag.
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- 1993
14. Cell-to-cell contact between normal fibroblasts and lymphoblasts deficient in lysosomal enzymes
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Paola Di Natale, Rossella Negri, Lucio Nitsch, Tiziana Annella, Aurora Daniele, DI NATALE, P, Annella, T, Daniele, Aurora, Negri, R, Nitsch, L., T., Annella, P., DI NATALE, Daniele, A, and Nitsch, Lucio
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Cell type ,Cell ,Cell Communication ,Iduronate Sulfatase ,Biology ,Cell–cell interaction ,Acetylglucosaminidase ,medicine ,Cell-cell interaction ,Humans ,Lymphocytes ,Lymphoblast ,Fibroblast ,Molecular Biology ,Mucopolysaccharidosis II ,chemistry.chemical_classification ,Fibroblasts ,Mucopolysaccharidoses ,Cell Transformation, Viral ,Lysosomal enzyme ,Enzyme assay ,Cell biology ,Apposition ,Microscopy, Electron ,Enzyme ,medicine.anatomical_structure ,Biochemistry ,chemistry ,biology.protein ,Molecular Medicine - Abstract
Human lymphoblasts deficient in iduronate sulfatase or in α-N-acetylglucosaminidase acquire discrete levels of enzyme activity after co-culture with human normal skin fibroblasts. This occurs by direct cell-to-cell contact and not by uptake of secreted fibroblast enzyme. The process is dependent on time and on the number of fibroblasts used. Electron-microscopic examination of the co-culture of the two cell types reveals extensive region of intimate contact. Fibroblastic projections appear frequently in close apposition witt lymphoblast invaginations; a diffuse micropinocytotic activity is evident only in fibroblastic cells.
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- 1992
15. Isolation, characterization and chromosomal localization of the gene encoding the mouse iduronate sulfatase
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DANIELE, Aurora, G. HERMANN, T. ANNELLA, P. DI NATALE, A. BALLABIO, Daniele, A, Hermann, G., Annella, T., DI NATALE, P., Ballabio, A., Daniele, Aurora, G., Hermann, T., Annella, P., DI NATALE, and A., Ballabio
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- 1992
16. Interaction between HDV and HBV infection in HBsAg-chronic carriers
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Evangelista Sagnelli, F. M. Felaco, A. Petruzziello, T. Annella, G. Pasauale, P. Filippini, P. Peinetti, L. Aprea, G. Giusti, F. Piccinino, M. Rapicetta, T. Stroffolini, P. Chionne, B. Sarrechia, Sagnelli, E, Felaco, Fm, Rapicetta, M, Stroffolini, T, Petruzziello, A, Annella, T, Chionne, P, Pasquale, Giuseppe, Filippini, Pietro, and Peinetti, P.
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Microbiology (medical) ,DNA Replication ,HBsAg ,Hepatitis B virus ,Cirrhosis ,Virus Replication ,medicine ,Humans ,Hepatitis, Chronic ,Hepatitis ,Hepatitis B Surface Antigens ,Chronic Active ,business.industry ,virus diseases ,General Medicine ,medicine.disease ,Hepatitis B ,digestive system diseases ,Hepatitis D ,HBcAg ,Infectious Diseases ,HBeAg ,Liver ,Immunology ,Viral disease ,Hepatitis Delta Virus ,business ,Asymptomatic carrier - Abstract
We studied the interaction between HBV and HDV infection in 149 consecutive subjects with HBsAg positive chronic hepatitis and in 22 chronic HBsAg healthy carriers. Liver HBcAg was detected in 52 (30.4%) of the 171 subjects. Of these 52, 35 were HBV-DNA and HBeAg positive, 11 HBV-DNA positive only; two HBeAg positive only and four were negative for both HBeAg and HBV-DNA. None of the 119 HBcAg-negative subjects had detectable HBV-DNA in serum. HD-Ag in hepatocytes was detected in 31 of the 171 subjects (18%); it was detectable in none of the 22 HBsAg healthy carriers, in four of the 56 patients with chronic persistent hepatitis (7.2%), in six of the 24 patients with chronic lobular hepatitis (25%), in 16 of the 40 patients with chronic active hepatitis (40%) and in five of the 29 with cirrhosis (17%). A presence of anti-HD in serum in the absence of liver HD-Ag was found in 54 of the 171 subjects (32%). This condition was observed not only in patients with a progressive disease (37.7% of chronic active hepatitis or cirrhosis and 33% of chronic lobular hepatitis), but also in healthy carriers (36%) and in chronic persistent hepatitis patients (21.4%). Liver HBcAg was detected in 6.4% of the 31 HD-Ag-positive patients, in 12.9% of the 54 HD-Ag-negative/anti-HD positive, but in 50% of the 86 with no marker of HDV infection. HDV appears to inhibit HBV genome and such inhibition may persist even when anti-HD is the only HDV marker detectable.
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- 1991
17. Opposing functions of Ki- and Ha-Ras genes in the regulation of redox signals
- Author
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Roberto Paternò, Ilaria Ciullo, Giovanni Cuda, Simona Damiano, Mariarosaria Santillo, Enrico V. Avvedimento, Giuseppe Iacomino, Rosalba Serù, Tiziana Annella, Antonio Feliciello, Evelina Mele, Mario Felice Tecce, Paolo Mondola, Silvana Cassano, Valeria Martignetti, Santillo, Mariarosaria, Mondola, Paolo, Seru', R, Annella, T, Cassano, S, Ciullo, I, Tecce, Mf, Iacomino, G, Damiano, S, Cuda, G, Paterno', Roberto, Martignetti, V, Mele, E, Feliciello, A, and Avvedimento, VITTORIO ENRICO
- Subjects
EXPRESSION ,PROTEINS ,Lysine ,Biology ,General Biochemistry, Genetics and Molecular Biology ,Cell Line ,Proto-Oncogene Proteins p21(ras) ,Mice ,Phosphatidylinositol 3-Kinases ,N-RAS ,Transcription (biology) ,Chlorocebus aethiops ,Animals ,SUPEROXIDE-DISMUTASE ,ras ,Phosphoinositide-3 Kinase Inhibitors ,Mitogen-Activated Protein Kinase 1 ,chemistry.chemical_classification ,Alanine ,Reactive oxygen species ,Mitogen-Activated Protein Kinase 3 ,DNA synthesis ,Agricultural and Biological Sciences(all) ,Superoxide Dismutase ,Biochemistry, Genetics and Molecular Biology(all) ,3T3 Cells ,Glutamic acid ,P21RAS ,Rats ,CAAX MOTIF ,APOPTOSIS ,Genes, ras ,Enzyme ,chemistry ,Biochemistry ,redox ,COS Cells ,PLASMA-MEMBRANE ,CELLS ,Mitogen-Activated Protein Kinases ,signaling ,Reactive Oxygen Species ,General Agricultural and Biological Sciences ,Oxidation-Reduction ,Signal Transduction ,Cysteine - Abstract
Ras p21 signaling is involved in multiple aspects of growth, differentiation, and stress response [1–2]. There is evidence pointing to superoxides as relays of Ras signaling messages. Chemicals with antioxidant activity suppress Ras-induced DNA synthesis. The inhibition of Ras significantly reduces the production of superoxides by the NADPH-oxidase complex [3]. Kirsten and Harvey are nonallelic Ras cellular genes that share a high degree of structural and functional homology. The sequences of Ki- and Ha-Ras proteins are almost identical. They diverge only in the 20-amino acid hypervariable domain at the COOH termini. To date, their functions remain indistinguishable [4]. We show that Ki- and Ha-Ras genes differently regulate the redox state of the cell. Ha-Ras-expressing cells produce high levels of reactive oxygen species (ROS) by inducing the NADPH-oxidase system. Ki-Ras, on the other hand, stimulates the scavenging of ROS by activating posttranscriptionally the mitochondrial antioxidant enzyme, Mn-superoxide dismutase (Mn-SOD), via an ERK1/2-dependent pathway. Glutamic acid substitution of the four lysine residues in the polybasic stretch at the COOH terminus of Ki-Ras completely abolishes the activation of Mn-SOD, although it does not inhibit ERK1/2-induced transcription. In contrast, an alanine substitution of the cysteine of the CAAX box has very little effect on Mn-SOD activity but eliminates ERK1/2- dependent transcription.
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