76 results on '"Polli C."'
Search Results
52. Jacalin-Activated Macrophages Exhibit an Antitumor Phenotype.
- Author
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Danella Polli C, Pereira Ruas L, Chain Veronez L, Herrero Geraldino T, Rossetto de Morais F, Roque-Barreira MC, and Pereira-da-Silva G
- Subjects
- Breast Neoplasms genetics, Breast Neoplasms pathology, Colonic Neoplasms genetics, Colonic Neoplasms pathology, Female, Gene Expression Regulation, Neoplastic, HT29 Cells, Humans, MCF-7 Cells, Macrophages metabolism, NF-kappa B genetics, Nitric Oxide Synthase Type II biosynthesis, Nitric Oxide Synthase Type II genetics, RNA, Messenger biosynthesis, Signal Transduction drug effects, Tumor Microenvironment drug effects, Tumor Microenvironment genetics, Breast Neoplasms drug therapy, Colonic Neoplasms drug therapy, Macrophages drug effects, Plant Lectins administration & dosage
- Abstract
Tumor-associated macrophages (TAMs) have an ambiguous and complex role in the carcinogenic process, since these cells can be polarized into different phenotypes (proinflammatory, antitumor cells or anti-inflammatory, protumor cells) by the tumor microenvironment. Given that the interactions between tumor cells and TAMs involve several players, a better understanding of the function and regulation of TAMs is crucial to interfere with their differentiation in attempts to skew TAM polarization into cells with a proinflammatory antitumor phenotype. In this study, we investigated the modulation of macrophage tumoricidal activities by the lectin jacalin. Jacalin bound to macrophage surface and induced the expression and/or release of mainly proinflammatory cytokines via NF-κB signaling, as well as increased iNOS mRNA expression, suggesting that the lectin polarizes macrophages toward the antitumor phenotype. Therefore, tumoricidal activities of jacalin-stimulated macrophages were evaluated. High rates of tumor cell (human colon, HT-29, and breast, MCF-7, cells) apoptosis were observed upon incubation with supernatants from jacalin-stimulated macrophages. Taken together, these results indicate that jacalin, by exerting a proinflammatory activity, can direct macrophages to an antitumor phenotype. Deep knowledge of the regulation of TAM functions is essential for the development of innovative anticancer strategies.
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- 2016
- Full Text
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53. Monocyte Migration Driven by Galectin-3 Occurs through Distinct Mechanisms Involving Selective Interactions with the Extracellular Matrix.
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Danella Polli C, Alves Toledo K, Franco LH, Sammartino Mariano V, de Oliveira LL, Soares Bernardes E, Roque-Barreira MC, and Pereira-da-Silva G
- Abstract
Monocyte migration into tissues, an important event in inflammation, requires an intricate interplay between determinants on cell surfaces and extracellular matrix (ECM). Galectin-3 is able to modulate cell-ECM interactions and is an important mediator of inflammation. In this study, we sought to investigate whether interactions established between galectin-3 and ECM glycoproteins are involved in monocyte migration, given that the mechanisms by which monocytes move across the endothelium and through the extravascular tissue are poorly understood. Using the in vitro transwell system, we demonstrated that monocyte migration was potentiated in the presence of galectin-3 plus laminin or fibronectin, but not vitronectin, and was dependent on the carbohydrate recognition domain of the lectin. Only galectin-3-fibronectin combinations potentiated the migration of monocyte-derived macrophages. In binding assays, galectin-3 did not bind to fibronectin, whereas both the full-length and the truncated forms of the lectin, which retains carbohydrate binding ability, were able to bind to laminin. Our results show that monocytes migrate through distinct mechanisms and selective interactions with the extracellular matrix driven by galectin-3. We suggest that the lectin may bridge monocytes to laminin and may also activate these cells, resulting in the positive regulation of other adhesion molecules and cell adhesion to fibronectin.
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- 2013
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54. Circulating tumour cells in locally advanced head and neck cancer: preliminary report about their possible role in predicting response to non-surgical treatment and survival.
- Author
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Buglione M, Grisanti S, Almici C, Mangoni M, Polli C, Consoli F, Verardi R, Costa L, Paiar F, Pasinetti N, Bolzoni A, Marini M, Simoncini E, Nicolai P, Biti G, and Magrini SM
- Subjects
- Antibodies, Monoclonal, Humanized, Cetuximab, Chi-Square Distribution, Disease Progression, Female, Head and Neck Neoplasms mortality, Head and Neck Neoplasms pathology, Humans, Italy, Male, Neoplasm Grading, Neoplasm Staging, Predictive Value of Tests, Prospective Studies, Risk Assessment, Risk Factors, Survival Analysis, Time Factors, Treatment Outcome, Antibodies, Monoclonal therapeutic use, Antineoplastic Agents therapeutic use, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Chemoradiotherapy, Head and Neck Neoplasms therapy, Neoplastic Cells, Circulating pathology
- Abstract
Background and Purpose: The mechanism of dissemination of locally advanced head and neck cancer (LAHNC) is far to be resolved. Circulating tumour cells (CTC) have been identified as a prognostic factor in metastatic breast and prostate cancer. This prospective multi-centric analysis studied the possible role of CTC identification in LAHNC., Materials and Methods: CTC were searched in 73 patients with LAHNC (oropharynx, n=39; nasopharynx, n=10; larynx, n=10; paranasal sinuses, n=6, of whom 3 with sinonasal undifferentiated carcinoma, SNUC; hypopharynx, n=5; oral cavity, n=3). All of them (apart from SNUC) had squamous cell cancers. The relationship between CTC positivity and other clinical prognostic factors has been investigated. Response to treatment and survival has been related with changes in CTC number during the treatment., Results: CTC were frequently identified in oro- and hypopharyngeal cancer and in SNUC. They were more frequent in stage IV than in stages I-III disease (18% versus 6%, p=NS (not significant)). Partial or complete response (CR) was related with the absence or disappearance of CTC during treatment (p=0.017). A decrease in the CTC number or their absence throughout the treatment seems also related with non-progressive disease, after both complete or incomplete remission and with the proportion of patients alive and NED (no evidence of disease) (p=0.009)., Conclusions: These preliminary data suggest a possible role of CTC determination in head and neck cancer. Additional and longer follow up data need to be collected to confirm these findings., (Copyright © 2012 Elsevier Ltd. All rights reserved.)
- Published
- 2012
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55. Identification of a novel Wilson disease gene mutation frequent in Upper Austria: a genetic and clinical study.
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Hofer H, Willheim-Polli C, Knoflach P, Gabriel C, Vogel W, Trauner M, Müller T, and Ferenci P
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- Adolescent, Adult, Austria, Child, Child, Preschool, Copper-Transporting ATPases, Female, Genotype, Humans, Male, Middle Aged, Pedigree, Young Adult, Adenosine Triphosphatases genetics, Cation Transport Proteins genetics, Hepatolenticular Degeneration diagnosis, Hepatolenticular Degeneration genetics, Mutation Rate
- Abstract
Wilson disease (WD), a disorder of copper metabolism is caused by mutations in the ATP7B gene, a copper transporting ATPase. In the present study we describe a novel mutation in exon 9 of the ATP7B gene. The ATP7B gene was analyzed for mutations by denaturing HPLC and direct sequencing. DNA from 100 healthy blood donors from the same geographic area was examined as control. Sixteen (7.4%) out of the 216 patients diagnosed with WD in Austria carried the newly identified R816S(c.2448G>T) point mutation in exon 9 (4 male, age: 19 (6-30) years, median (range)). One patient was homozygous for R816S(c.2448G>T). Thirteen patients were compound heterozygotes (p.H1069Q(c.3207C>A)/R816S(c.2448G>T) (N=6), P539L/R816S(c.2448G>T) (N=3), each one G710S/R816S(c.2448G>T), P767P(2299insC)/R816S(c.2448G>T), W779G/R816S(c.2448G>T), T1220M/R816S(c.2448G>T)). In two patients no second mutation was identified. Interestingly, all but three of the patients originated within a distinct geographical area in Austria. Eleven patients presented with hepatic disease, 3 patients with neurological disease and 2 were asymptomatic sisters of an index case. A liver biopsy was available in 14 patients. Three patients showed advanced liver disease with liver transplantation for acute hepatic failure in two. The remaining patients had only mild histological changes, most commonly steatosis. Chronic hepatitis was described in five patients. Kayser-Fleischer ring was present in five patients. None of the 100 healthy controls carried the mutation. We describe a novel mutation in the ATP7B gene, occurring in patients originated from a distinct geographical area in Austria associated with a variable course of the disease.
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- 2012
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56. M-ficolin and leukosialin (CD43): new partners in neutrophil adhesion.
- Author
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Moreno-Amaral AN, Gout E, Danella-Polli C, Tabarin F, Lesavre P, Pereira-da-Silva G, Thielens NM, and Halbwachs-Mecarelli L
- Subjects
- Complement Activation physiology, Humans, Lectins immunology, N-Acetylneuraminic Acid metabolism, Neutrophils immunology, Protein Binding, Protein Transport, Ficolins, Cell Adhesion immunology, Lectins metabolism, Leukosialin metabolism, Neutrophils metabolism
- Abstract
M-ficolin specificity for sialylated ligands prompted us to investigate its interactions with the main membrane sialoprotein of human neutrophils, CD43. rM-ficolin bound CD43 and prevented the access of anti-CD43 mAb. Moreover, rM-ficolin reacted exclusively with CD43 on Western blots of neutrophil lysate. We confirmed that M-ficolin is secreted by fMLP-activated neutrophils, and this endogenous M-ficolin also binds to CD43 and competes with anti-CD43 mAb. Anti-CD43 antibody cross-linking or fMLP resulted in M-ficolin and CD43 colocalization on polarized neutrophils. The binding of rM-ficolin to resting neutrophils induced cell polarization, adhesion, and homotypic aggregation as anti-CD43 mAb. The M-ficolin Y271F mutant, unable to bind sialic acid, neither reacted with neutrophils nor modulated their functions. Finally, rM-ficolin activated the lectin complement pathway on neutrophils. These results emphasize a new function of M-ficolin, different from ficolin pathogen recognition, i.e., a participation to neutrophil adhesion potentially important in early inflammation, as nanomolar agonist concentrations are sufficient to mobilize M-ficolin to the neutrophil surface. This multivalent lectin could then endow the antiadhesive CD43, essentially designed to prevent leukocyte aggregation in the blood flow, with new adhesive properties and explain, at least in part, dual-adhesive/antiadhesive roles of CD43 in neutrophil recruitment.
- Published
- 2012
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57. Association between single nucleotide polymorphisms in the XRCC1 and RAD51 genes and clinical radiosensitivity in head and neck cancer.
- Author
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Pratesi N, Mangoni M, Mancini I, Paiar F, Simi L, Livi L, Cassani S, Buglione M, Grisanti S, Almici C, Polli C, Saieva C, Magrini SM, Biti G, Pazzagli M, and Orlando C
- Subjects
- Adult, Alleles, Chi-Square Distribution, DNA Repair, Female, Gene Frequency, Genotype, Glutathione S-Transferase pi genetics, Humans, Male, Proportional Hazards Models, Radiation Injuries genetics, Radiotherapy Dosage, Reactive Oxygen Species, Risk Factors, X-ray Repair Cross Complementing Protein 1, Carcinoma, Squamous Cell genetics, Carcinoma, Squamous Cell radiotherapy, DNA-Binding Proteins genetics, Head and Neck Neoplasms genetics, Head and Neck Neoplasms radiotherapy, Polymorphism, Single Nucleotide, Rad51 Recombinase genetics, Radiation Tolerance genetics
- Abstract
Purpose: Individual variability in radiosensitivity is large in cancer patients. Single nucleotide polymorphisms (SNPs) in genes involved in DNA repair and in protection against reactive oxygen species (ROS) could be responsible for such cases of radiosensitivity. We investigated the association between the occurrence of acute reactions in 101 patients with squamous cell carcinoma of the head and neck (SCCHN) after radiotherapy (RT) and five genetic polymorphisms: XRCC1 c.1196A>G, XRCC3 c.722C>T, RAD51 (c.-3429G>C, c.-3392G>T), and GSTP1 c.313A>G., Materials and Methods: Genetic polymorphisms were detected by high resolution melting analysis (HRMA). The development of acute reactions (oral mucositis, skin erythema and dysphagia) associated with genetic polymorphisms was modeled using Cox proportional hazards, accounting for biologically effective dose (BED)., Results: Development of grade ≥2 mucositis was increased in all patients (chemo-radiotherapy and radiotherapy alone) with XRCC1-399Gln allele (HR=1.72). The likelihood of developing grade ≥2 dysphagia was higher in carriers of RAD51 c.-3429 CC/GC genotypes (HR=4.00). The presence of at least one SNP or the co-presence of both SNPs in XRCC1 p.Gln399Arg /RAD51 c.-3429 G>C status were associated to higher likelihood of occurrence of acute toxicities (HR=2.03)., Conclusions: Our findings showed an association between genetic polymorphisms, XRCC1 c.1196A>G and RAD51 c.-3429 G>C, and the development of radiation-induced toxicities in SCCHN patients., (Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.)
- Published
- 2011
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58. Cone beam CT image guidance for intracranial stereotactic treatments: comparison with a frame guided set-up.
- Author
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Masi L, Casamassima F, Polli C, Menichelli C, Bonucci I, and Cavedon C
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- Humans, Reproducibility of Results, Sensitivity and Specificity, Brain Neoplasms diagnostic imaging, Brain Neoplasms radiotherapy, Cone-Beam Computed Tomography methods, Imaging, Three-Dimensional methods, Immobilization methods, Radiosurgery methods, Surgery, Computer-Assisted methods
- Abstract
Purpose: An analysis is performed of the setup errors measured by a kV cone beam computed tomography (CBCT) for intracranial stereotactic radiotherapy (SRT) patients immobilized by a thermoplastic mask and a bite-block and positioned using stereotactic coordinates. We evaluated the overall positioning precision and accuracy of the immobilizing and localizing systems. The potential of image-guided radiotherapy to replace stereotactic methods is discussed., Methods and Materials: Fifty-seven patients received brain SRT. After a frame-guided setup, before each fraction (131 fractions), a CBCT was acquired and the detected displacements corrected online. Translational and rotational errors were analyzed calculating overall mean and standard deviation. A separate analysis was performed for bite-block (in conjunction with mask) and for simple thermoplastic mask. Interobserver variability for CBCT three-dimensional registration was assessed. The residual error after correction and intrafractional motion were calculated., Results: The mean module of the three-dimensional displacement vector was 3.0 +/- 1.4 mm. Setup errors for bite block and mask were smaller (2.9 +/- 1.3 mm) than those for thermoplastic mask alone (3.2 +/- 1.5 mm), but statistical significance was not reached (p = 0.15). Interobserver variability was negligible. The maximum margin calculated for residual errors and intra fraction motion was small but not negligible (1.57 mm)., Conclusions: Considering the detected setup errors, daily image guidance is essential for the efficacy of SRT treatments when mask immobilization is used, and even when a bite-block is used in conjunction. The frame setup is still used as a starting point for the opportunity of rotational corrections. Residual margins after on-line corrections must be evaluated.
- Published
- 2008
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59. Relevance of biologically equivalent dose values in outcome evaluation of stereotactic radiotherapy for lung nodules.
- Author
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Casamassima F, Masi L, Bonucci I, Polli C, Menichelli C, Gulisano M, Pacini S, Aterini S, and Cavedon C
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- Aged, Carcinoma, Non-Small-Cell Lung diagnostic imaging, Carcinoma, Non-Small-Cell Lung mortality, Carcinoma, Non-Small-Cell Lung pathology, Dose Fractionation, Radiation, Female, Follow-Up Studies, Humans, Lung Neoplasms diagnostic imaging, Lung Neoplasms mortality, Lung Neoplasms pathology, Male, Radiography, Relative Biological Effectiveness, Solitary Pulmonary Nodule diagnostic imaging, Solitary Pulmonary Nodule mortality, Solitary Pulmonary Nodule pathology, Survival Rate, Treatment Outcome, Carcinoma, Non-Small-Cell Lung surgery, Lung Neoplasms surgery, Radiosurgery, Solitary Pulmonary Nodule surgery
- Abstract
Purpose: Different biologically equivalent dose (BED) values associated with stereotactic radiotherapy (SRT) of patients with primary and metastatic pulmonary nodules were studied. The BED values were calculated for tumoral tissue and low alpha/beta ratio, assuming that better local response could be obtained by using stereotactic high-BED treatment., Methods and Materials: Fifty-eight patients with T1-T3 N0 non-small-cell lung cancer and 46 patients with metastatic lung nodules were treated with SRT. The BED was calculated for alpha/beta ratios of 3 and 10. Overall survival (OS) was assessed according to Kaplan-Meier and appraised as a function of three BED levels: low (30-50 Gy), medium (50-70 Gy), and high (70-98 Gy; alpha/beta = 10)., Results: The OS rates for all 104 patients at 12, 24, and 36 months were 73%, 48.3%, and 35.8%, respectively. Local response greater than 50% for low, medium, and high BED values was observed in 54%, 47%, and 73%, respectively. In the high-BED treated group, OS rates at 12, 24, and 36 months (80.9%, 70%, and 53.6%, respectively) were significantly improved compared with low- (69%, 46.1%, and 30.7%, respectively) and medium-BED (67%, 28%, and 21%, respectively) treated patients. Results are also discussed in terms of BED calculated on alpha/beta 3 Gy characteristic of the microcapillary bed. No acute toxicity higher than Grade 1 was observed., Conclusions: Radioablation of pulmonary neoplastic nodules may be achieved with SRT delivered by using a high-dose fraction with high BED value.
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- 2008
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60. Evolution of Crohn's disease-associated Nod2 mutations.
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Gasche C, Nemeth M, Grundtner P, Willheim-Polli C, Ferenci P, and Schwarzenbacher R
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- Alleles, Crohn Disease epidemiology, DNA Mutational Analysis, Evolution, Molecular, Exons, Genetic Variation, Humans, Polymorphism, Single Nucleotide genetics, Crohn Disease genetics, Genetics, Population, Mutation genetics, Nod2 Signaling Adaptor Protein genetics, Selection, Genetic
- Abstract
Several lines of evidence have confirmed the importance of Nod2 mutations for disease susceptibility in Crohn's disease. For tracing Nod2 evolution, exons 4a, 4e, 8, and 12 mutations were screened in a collection of 1,064 DNA samples from 52 worldwide populations. The overall allele frequency was 7.5% for single nucleotide polymorphism (SNP)5, 0.2% for SNP8, 0.3% for SNP12, and 0.4% for SNP13. Nod2 mutations are mainly Caucasian alleles with strong distribution dissimilarity between single populations and major geographical regions. This regional diversity of Nod2 mutations within Europe points to the regional existence of selection pressure (possibly through dairy-associated bacterial infections within Neolithic cattle farming populations). The SNP5 gradient between Africa and the Middle East and its absence in Asian and Native American populations indicate that the evolution of this variant occurred in the Middle East. As mutations in exons 4e, 8, and 12 were only found in association with SNP5, this variant may have allowed selection pressure to arise.
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- 2008
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61. On-line image guidance for frameless stereotactic radiotherapy of lung malignancies by cone beam CT: comparison between target localization and alignment on bony anatomy.
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Masi L, Casamassima F, Menichelli C, Pasciuti K, Doro R, Polli C, D'imporzano E, and Bonucci I
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- Bone and Bones diagnostic imaging, Humans, Lung Neoplasms diagnostic imaging, Movement, Observer Variation, Radiosurgery, Respiration, Cone-Beam Computed Tomography, Lung Neoplasms surgery, Online Systems
- Abstract
Introduction: Free-breathing stereotactic radiotherapy for lung malignancies requires reliable prediction of respiratory motion and accurate target localization. A protocol was adopted for reproducibility and reduction of respiratory motion and for target localization by CBCT image guidance. Tumor respiratory displacements and tumor positioning errors relative to bony anatomy alignment are analyzed., Materials and Method: Image guided SRT was performed for 99 lung malignancies. Two groups of patients were considered: group A did not perform any breathing control; group B controlled visually their respiratory cycle and volumes on an Active Breathing Coordinator (ABC) monitor during the acquisition of simulation CT and CBCT, and treatment delivery. GTV on end inhale and exhale CT data sets were fused in an ITV and the extent of tumor motion evaluated between these 2 phases. A pre-treatment CBCT was acquired and aligned to the reference CT using bony anatomy; for tumor positioning the ITV contour on the reference CT was matched to the visible tumor on CBCT. Interobserver variability of tumor positioning was evaluated. ITV and CBCT tumor dimensions were compared., Results: 3D tumor breathing displacement (mean+/-SD) was significantly higher for group A (14.7+/-9.9 mm) than for group B (4.7+/-3.1 mm). The detected differences between tumor and bony structure alignment below 3 mm were 68% for group B and 45% for group A, reaching statistical significance. Interobserver variability was 1.7+/-1.1 mm (mean+/-SD). Dimensions of tumor image on CBCT were consistent with ITV dimensions for group B (max difference 14%)., Conclusions: The adopted protocol seems effective in reducing respiratory internal movements and margin. Tumor positioning errors relative to bony anatomy are also reduced. However bony anatomy as a surrogate of the target may still lead to some relevant positioning errors. Target visualization on CBCT is essential for an accurate localization in lung SRT.
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- 2008
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62. In situ investigation of the oxidative addition in homogeneous Pd catalysts by synchronised time resolved UV-Vis/EXAFS.
- Author
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Guilera G, Newton MA, Polli C, Pascarelli S, Guinó M, and Hii KK
- Abstract
Simultaneous structuro-kinetic information obtained via time resolved stopped-flow/UV-Vis spectroscopy/dispersive EXAFS (EDE) experiments elucidated a two-step process for the addition of iodobenzene to [(Ph3P)2Pd(dba)].
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- 2006
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63. Late treatment-related complications in 214 patients with extremity soft-tissue sarcoma treated by surgery and postoperative radiation therapy.
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Livi L, Santoni R, Paiar F, Bastiani P, Beltrami G, Caldora P, Capanna R, De Biase P, Detti B, Fondelli S, Meldolesi E, Pertici M, Polli C, Simontacchi G, and Biti G
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- Adult, Aged, Brachytherapy, Combined Modality Therapy, Extremities, Female, Fibrosis etiology, Follow-Up Studies, Humans, Male, Middle Aged, Peripheral Nervous System Diseases etiology, Sarcoma radiotherapy, Sarcoma surgery, Soft Tissue Neoplasms radiotherapy, Soft Tissue Neoplasms surgery, Fractures, Bone etiology, Sarcoma therapy, Soft Tissue Neoplasms therapy
- Abstract
Background: We assessed the occurrence of long-bone fracture and other side effects in a group of 214 consecutive patients who underwent radical excision for soft-tissue sarcoma of the limb followed by postoperative irradiation., Methods: Two hundred fourteen patients underwent postoperative irradiation after radical excision of soft-tissue sarcoma of the limb; 156 (73%) received postoperative brachytherapy (BRT) plus external-beam radiation therapy (EBRT), and 58 (27%) underwent postoperative EBRT only. All patients were followed-up for a median time of 4.5 years (range 3 months to 10 years)., Results: Seven patients developed bone fracture, which is considered severe morbidity; time between surgery and occurrence of fracture ranged between 10 and 72 months (average 31). Severe sclerosis with impairment of limb function was diagnosed in 5 and peripheral nerve damage in 3 patients. Wound complications were detected in 8 patients., Conclusions: In our series, no statistically significant correlation between bone fracture and clinical features or "technical" parameters was found, but all of the patients who experienced bone fracture (7 of 7) were postmenopausal women >55 years old.
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- 2006
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64. Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. I. The case of T1N0 disease.
- Author
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Cellai E, Frata P, Magrini SM, Paiar F, Barca R, Fondelli S, Polli C, Livi L, Bonetti B, Vitali E, De Stefani A, Buglione M, and Biti G
- Subjects
- Adult, Aged, Aged, 80 and over, Analysis of Variance, Carcinoma, Squamous Cell pathology, Female, Humans, Italy, Laryngeal Neoplasms pathology, Male, Middle Aged, Neoplasms, Second Primary etiology, Proportional Hazards Models, Radiation Injuries pathology, Radiotherapy Dosage, Retrospective Studies, Sex Factors, Treatment Outcome, Carcinoma, Squamous Cell radiotherapy, Glottis pathology, Laryngeal Neoplasms radiotherapy
- Abstract
Purpose: To retrospectively evaluate local control rates, late damage incidence, functional results, and second tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T1 glottic cancer., Methods and Materials: A total of 831 T1 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia-Istituto del Radio "O. Alberti" (BS) were studied. Actuarial cumulative local control probability (LC), disease-specific (DSS), and overall survival (OS) rates have been calculated and compared in the different clinical and therapeutic subgroups with both univariate and multivariate analysis. Types of relapse and their surgical salvage have been evaluated, along with the functional results of treatment. Late damage incidence and second tumor cumulative probability (STP) have been also calculated., Results: In the entire series, 3-, 5-, and 10-year OS was equal to 86%, 77%, and 57%, respectively. Corresponding values for LC were 86%, 84%, and 83% and for DSS 96%, 95%, and 93%, taking into account surgical salvage of relapsed cases. Eighty-seven percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were: male gender, earlier treatment period, larger tumor extent, anterior commissure involvement, and the use of Cobalt 60. At multivariate analysis, only gender, tumor extent, anterior commissure involvement, and beam type retained statistical significance. Higher total doses and larger field sizes are significantly related (logistic regression) with a higher late damage incidence. Scatterplot analysis of various combinations of field dimensions and total dose showed that field dimensions >35 and <49 cm2, together with doses of >65 Gy, offer the best local control results together with an acceptably low late damage incidence. Twenty-year STP was equal to 23%, with second tumor deaths being more frequent than larynx cancer deaths (67 of 831 vs. 46/831)., Conclusion: The results of this study support the opinion, suggested by some international guidelines, that radiotherapy is standard treatment for T1 glottic cancer. Better results are obtained in patients with less extended disease and with 4-6 MV photon beams. The use of doses in excess of 65 Gy and of field sizes of 36-49 cm2 is probably the best technical choice available. Late damage is infrequent, but careful follow-up is warranted to detect early not only relapses (because conservative salvage surgery is feasible), but also second malignant tumors, which constitute the main cause of death in these patients and are potentially curable.
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- 2005
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65. Radical radiotherapy for early glottic cancer: Results in a series of 1087 patients from two Italian radiation oncology centers. II. The case of T2N0 disease.
- Author
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Frata P, Cellai E, Magrini SM, Bonetti B, Vitali E, Tonoli S, Buglione M, Paiar F, Barca R, Fondelli S, Polli C, Livi L, and Biti G
- Subjects
- Adult, Aged, Aged, 80 and over, Analysis of Variance, Carcinoma, Squamous Cell pathology, Carcinoma, Squamous Cell surgery, Female, Humans, Italy, Laryngeal Neoplasms pathology, Laryngeal Neoplasms surgery, Male, Middle Aged, Neoplasms, Second Primary etiology, Radiation Injuries pathology, Radiotherapy Dosage, Retrospective Studies, Salvage Therapy, Carcinoma, Squamous Cell radiotherapy, Glottis, Laryngeal Neoplasms radiotherapy
- Abstract
Purpose: To retrospectively evaluate local control rates, late damage incidence, functional results, and second-tumor occurrence according to the different patient, tumor, and treatment features in a large bi-institutional series of T2 glottic cancer., Methods and Materials: A total of 256 T2 glottic cancer cases treated consecutively with radical intent at the Florence University Radiation Oncology Department (FLO) and at the Radiation Oncology Department of the University of Brescia, Istituto del Radio "O. Alberti" (BS) were studied. Cumulative probability of local control (LC), disease-specific survival (DSS), and overall survival (OS) rates were calculated and compared in the different clinical and therapeutic subgroups by both univariate and multivariate analysis. Types of relapse and their surgical salvage were evaluated, along with the functional results of treatment. Late-damage incidence and second-tumor cumulative probability (STP) were also calculated., Results: In the entire series, 3-year, 5-year, and 10-year OS rates were, respectively, 73%, 59%, and 37%. Corresponding values for cumulative LC probability were 73%, 73%, and 70% and for DSS, 89%, 86%, and 85%, taking into account surgical salvage of relapsed cases. Seventy-three percent of the patients were cured with function preserved. Main determinants of a worse LC at univariate analysis were larger tumor extent and impaired cord mobility. At multivariate analysis, the same factors retained statistical significance. Twenty-year STP was 23%, with second-tumor deaths less frequent than larynx cancer deaths (20 of 256 vs. 30 of 256). Incidence of late damage was higher in the first decade of accrual (22%) than in the last decade (10%, p = 0.03); the same was true for severe late damage (9% vs. 1.8%)., Conclusion: Present-day radical radiotherapy can be considered a standard treatment for T2 glottic cancer. Better results are obtained in patients with less extended disease. Late damage is relatively infrequent, but a careful follow-up is warranted for early detection not only of relapses (because salvage surgery is feasible) but also of second malignant tumors, which constitute a relevant but not the leading cause of death in these patients and are potentially curable.
- Published
- 2005
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66. Toll-like receptor 4 and NOD2/CARD15 mutations in Hungarian patients with Crohn's disease: phenotype-genotype correlations.
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Lakatos PL, Lakatos L, Szalay F, Willheim-Polli C, Osterreicher C, Tulassay Z, Molnar T, Reinisch W, Papp J, Mozsik G, and Ferenci P
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- Adult, Female, Genotype, Humans, Hungary, Male, Middle Aged, Nod2 Signaling Adaptor Protein, Toll-Like Receptor 4, Toll-Like Receptors, Crohn Disease genetics, Intracellular Signaling Peptides and Proteins genetics, Membrane Glycoproteins genetics, Mutation, Phenotype, Receptors, Cell Surface genetics
- Abstract
Aim: To determine common NOD2/CARD15 mutations and TLR4 D299G polymorphism in Hungarian patients with CD., Methods: A total of 527 unrelated patients with CD (male/female: 265/262, age: 37.1 (SD 7.6) years) and 200 healthy subjects were included. DNA was screened for possible NOD2/CARD15 mutations by denaturing high-performance liquid chromatography (confirmed by direct sequencing). TLR4 D299G was tested by PCR-RFLP., Results: NOD2/CARD15 mutations were found in 185 patients (35.1%) and in 33 controls (16.5%, P<0.0001). SNP8/R702W (10.8% vs 6%, P = 0.02), SNP13/3020insC (19.4% vs 5%, P<0.0001) and exon4 R703C (2.1% vs 0%, P = 0.02) mutations were more frequent in CD, while the frequency of SNP12/G908R was not increased. The frequency of TLR4 D299G was not different (CD: 9.9% vs controls: 12.0%). Variant NOD2/CARD15 allele was associated with an increased risk for CD (OR(het) = 1.71, 95%CI = 1.12-2.6, P = 0.0001, OR(two-risk alleles) = 25.2, 95%CI = 4.37-8, P<0.0001), early disease onset (carrier: 26.4 years vs non-carrier: 29.8 years, P = 0.0006), ileal disease (81.9% vs 69.5%, OR = 1.99, 95%CI = 1.29-3.08, P = 0.02, presence of NOD2/CARD15 and TLR4: 86.7% vs 64.8%), stricturing behavior (OR = 1.69, 95%CI = 1.13-2.55, P = 0.026) and increased need for resection (OR=1.71, 95%CI: 1.13-2.62, P = 0.01), but not with duration, extra-intestinal manifestations, familial disease or smoking. TLR4 exhibited a modifier effect: age of onset in wt/TLR4 D299G carriers: 27.4 years vs NOD2mut/TLR D299G: 23 years (P = 0.06), in NOD2mut/wt: 26.7 years., Conclusion: These results confirm that variant NOD2/CARD15 (R702W, R703C and 3020insC) alleles are associated with earlier disease onset, ileal disease, stricturing disease behavior in Hungarian CD patients. In contrast, although the frequency of TLR4 D299G polymorphism was not different from controls, NOD2/TLR4 mutation carriers tended to present at earlier age.
- Published
- 2005
- Full Text
- View/download PDF
67. [NOD2/CARD15 mutations and genotype-phenotype correlations in patients with Crohn's disease. Hungarian multicenter study].
- Author
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Lakatos L, Lakatos PL, Willheim-Polli C, Reinisch W, Ferenci P, Tulassay Z, Molnár T, Kovács A, Papp J, and Szalay F
- Subjects
- Adult, Arthritis etiology, Case-Control Studies, Cholangitis, Sclerosing etiology, Eye Diseases etiology, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Hungary epidemiology, Male, Nod2 Signaling Adaptor Protein, Phenotype, Sequence Analysis, DNA, Skin Diseases etiology, Smoking epidemiology, Carrier Proteins genetics, Crohn Disease complications, Crohn Disease genetics, Intracellular Signaling Peptides and Proteins, Mutation
- Abstract
Unlabelled: Recently mutations of the NOD2/CARD15 gene were identified as genetic markers for Crohn's disease (CD). It has also been suggested that the presence of mutation may influence the phenotype of the disease. The aim of this study was to determine the frequency of common NOD2/CARD15 mutations in Hungarian Crohn's patients., Patients and Methods: DNA was obtained from 142 pts with Crohn's disease (70 male and 72 female, mean age: 36.2 yrs) and of 115 healthy subjects. Clinical data were obtained by filling in a questionnaire by the physician. DNA was screened for possible mutations by denaturing HPLC (WAVE Nucleic acid fragment analysis systems, Cheshire, UK) using published primers (Lesage et al, Am J Hum Gen 2002) for SNP's 8, 12, and 13. Mutations were then confirmed by direct sequencing on a ABI Prism 310 Genetic Analyzer (Perkin Elmer; Norwalk, USA)., Results: Mutations of NOD2/CARD15 were significantly more frequent in patients (n = 42, 29.6%) than in controls (11.3%, p = 0.0007, OR = 3.3, 95% CI = 1.7-6.5). R702W and 3020insC mutations were significantly more common in IBD compared to controls (4.3% and 2.6%); 18 patients had the R702W mutation (12.7%, p = 0.001, 13 homozygous, one homozygous for R703C) and 22 the 3020insC (15.9%, p = 0.001, 4 homozygous). 7 patients (4.9%) were heterozygous for the G908R, which was not different from the controls (4.3%). 5 patients were compound heterozygous. The allele frequency of R702W (11.6% vs. 4.3%, p = 0.0026, OR = 5.9, 95% CI: 2.3-14.9) and 3020insC (9.1% vs. 2.6% p = 0.004, OR = 7.6, 95% CI = 2.4-24.0) was significantly higher in Crohn's disease compared to the controls. Age at presentation was not different between carriers and non-carriers (26.7 +/- [SD] 10.3 yrs vs. 27.7 +/- 11.8 yrs). There was a tendency of ileal location to be more common in carriers of the mutation (40.5% vs. 29.0%), while colonic location was less frequent (16.7% vs. 44%). The presence of the mutation did not affect disease behaviour (carrier: inflammatory: 30.9%, stenosing: 26.2%, penetrating: 42.9%, non-carrier: inflammatory: 36%, stenosing: 27%, penetrating: 37%). Among the extraintestinal manifestations arthritis (30.1% vs. 47%, p = 0.05) and primary sclerosing cholangitis (0% vs. 9%, p = 0.047%) was significantly less frequent in carriers of the mutation., Conclusions: In concordance with European data we found a high number of NOD2/CARD15 R702W and 3020insC mutations in Hungarian patients with Crohn's disease. The G908R mutation was uncommon in Hungarian Crohn's patients. The presence of the mutation was associated with ileal but not with fibrostenosing disease and extraintestinal manifestations were less common in carriers of the mutation.
- Published
- 2004
68. Representation of two geometric features of the environment in the domestic chick ( Gallus gallus).
- Author
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Tommasi L and Polli C
- Subjects
- Animals, Male, Chickens physiology, Cues, Feeding Behavior physiology, Pattern Recognition, Visual physiology
- Abstract
We report experiments based on a novel test in domestic chicks ( Gallus gallus), designed to examine the encoding of two different geometric features of an enclosed environment: relative lengths of the walls and amplitude of the corners. Chicks were trained to search for a food reward located in one corner of a parallelogram-shaped enclosure. Between trials, chicks were passively disoriented and the enclosure was rotated, making reorientation possible only on the basis of the internal spatial structure of the enclosure. In order to reorient, chicks could rely on two sources of information: the relative lengths of the walls of the enclosure (associated to their left-right sense order) and the angles subtended by walls at corners. Chicks learned the task choosing equally often the reinforced corner and its rotational equivalent. Results of tests carried out in novel enclosures, the shapes of which were chosen ad hoc (1) to induce reorientation based only on the ratio of walls lengths plus sense (rectangular enclosure), or (2) to induce reorientation based only on corner angles (rhombus-shaped enclosure), suggested that chicks encoded both features of the environment. In a third test, in which chicks faced a conflict between these geometric features (mirror parallelogram-shaped enclosure), reorientation seemed to depend on the salience of corner angles. These results shed light on the elements of the environmental geometry which control spatial reorientation, and broaden the knowledge on the geometric representation of space in animals.
- Published
- 2004
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69. Mutations of the HFE gene in patients with hepatocellular carcinoma.
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Cauza E, Peck-Radosavljevic M, Ulrich-Pur H, Datz C, Gschwantler M, Schöniger-Hekele M, Hackl F, Polli C, Rasoul-Rockenschaub S, Müller C, Wrba F, Gangl A, and Ferenci P
- Subjects
- Arthralgia genetics, Female, Gene Frequency, Hemochromatosis Protein, Hepatitis C, Chronic genetics, Heterozygote, Homozygote, Humans, Liver Cirrhosis genetics, Male, Carcinoma, Hepatocellular genetics, Hemochromatosis genetics, Histocompatibility Antigens Class I genetics, Liver Neoplasms genetics, Membrane Proteins genetics, Mutation, Missense
- Abstract
Objective: Hepatocellular carcinoma (HCC) is a late consequence of severe liver disease. Patients with genetic hemochromatosis may be at risk for HCC, but limited information is available on the relationship of HCC and heterozygosity for the HFE gene mutations., Methods: HFE mutations (C282Y and H63D) were assessed in 162 consecutive patients (131 men/31 women) with HCC. A total of 159 patients had cirrhosis. The most common etiologies of cirrhosis were chronic viral hepatitis (hepatitis C 39%, hepatitis B 9%) and alcoholic liver disease (36%)., Results: Five patients were C282Y homozygotes, four C282Y/H63D compound heterozygotes, and three H63D homozygotes. The C282Y and H63D allele frequencies in HCC were 8.3 (95% confidence limit = 5.3-11.3) and 11.1 (7.8-14.6), respectively, and not different from previously published data in healthy subjects or patients with chronic hepatitis C in Austria. Furthermore, there was no difference in the age at diagnosis in patients with or without HFE gene mutations. C282Y homozygotes had a 19-fold increased risk to develop HCC. In contrast, all other HFE allele constellations were not associated with such a risk., Conclusions: Except for C282Y homozygotes, HFE gene mutations do not increase the risk to develop HCC in patients with cirrhosis.
- Published
- 2003
- Full Text
- View/download PDF
70. Liver pathology in compound heterozygous patients for hemochromatosis mutations.
- Author
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Schöniger-Hekele M, Müller C, Polli C, Wrba F, Penner E, and Ferenci P
- Subjects
- Adolescent, Adult, Aged, DNA Mutational Analysis, Electrophoresis, Polyacrylamide Gel, Female, Ferritins blood, Hemochromatosis complications, Hemochromatosis genetics, Humans, Liver Diseases etiology, Liver Diseases genetics, Male, Middle Aged, Mutation, Polymerase Chain Reaction, Transferrin analysis, Hemochromatosis pathology, Heterozygote, Liver pathology, Liver Diseases pathology
- Abstract
Background: While hepatic pathology of homozygous carriers of the C282Y mutation of the HFE haemochromatosis gene is well defined, the impact of the C282Y/H63D compound heterozygous carrier state is unknown., Aims: To evaluate the range of hepatic pathology in C282Y/H63D compound heterozygous patients., Patients: 25 C282Y/H63D compound heterozygous patients with and without known underlying liver disease underwent liver biopsies for evaluation or abnormal liver tests. Eleven cadaveric liver donors with HFE wild type served as controls., Methods: Mutations in the HFE gene were detected by polyacrylamide gel electrophoresis (PAGE) separation of digested polymerase chain reaction (PCR)-amplificates. The extent of light microscopic changes of liver architecture were studied on haematoxylin, eosin (H. E.) stains. In addition, the extent and the distribution of iron deposition was graded on Prussian blue-stained sections and hepatic iron was quantified by atom absorption spectroscopy. Serum ferritin concentration and the transferrin saturation index were measured using routine laboratory methods., Results: Patients without underlying liver disease (n = 15): Hepatic inflammation was seen in only 8% but fibrosis was found in 36% of compound heterozygous patients. Eighty six percent of those patients had stainable iron predominantly found in Rappaport's zone 1 and 2, but all had a liver iron-index < 1.9. Transferrin saturation was found elevated in 36% of compound heterozygous patients. Patients with liver fibrosis showed significantly higher ferritin levels than patients without liver fibrosis (1110 ng/mL versus 307 ng/mL, p < 0.05). Patients with underlying disease (n = 10): In compound heterozygous patients, 77% had hepatic inflammation and 88% fibrosis. Stainable iron (44%) was less frequently found than in patients without underlying liver disease. Hepatic iron-index in patients with underlying liver disease was always below 1.17; transferrin saturation was elevated in only 22% of the compound heterozygous patients. Histologic hepatic iron-index was significantly lower in patients with underlying disease (median 0.047) as compared to patients without underlying liver disease (median 0.274, P < 0.05)., Conclusions: The underlying liver disease determines the extent of hepatic pathology seen in livers of compound heterozygous patients. However, considerable histologic fibrosis can also be found in compound heterozygous patients without underlying liver disease.
- Published
- 2002
- Full Text
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71. Common mutations of ATP7B in Wilson disease patients from Hungary.
- Author
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Firneisz G, Lakatos PL, Szalay F, Polli C, Glant TT, and Ferenci P
- Subjects
- Adult, Base Sequence, Copper-Transporting ATPases, DNA Mutational Analysis, Female, Gene Frequency, Haplotypes, Humans, Hungary, Male, Microsatellite Repeats, Adenosine Triphosphatases genetics, Cation Transport Proteins genetics, Hepatolenticular Degeneration genetics, Mutation
- Abstract
Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The H1069Q mutation in exon 14 of ATP7B is far the most frequent in Wilson patients of European origin. Mutations in exon 8 and 15 are also common among the over 150 described mutations in the WD gene. The aim was to investigate the frequency of these common WD gene mutations in Hungarian patients. A total of 42 patients with WD from 39 Hungarian families were examined. The H1069Q mutation was assessed by a seminested polymerase chain reaction (PCR)-based restriction fragment length polymorphism (RFLP) assay, while mutations in exons 8, 13, 15, and 18 of WD gene were identified by sequencing. In addition, haplotype analysis was performed using three common microsatellite markers (D13S314, D13S301, D13S316). The H1069Q mutation was found in 27 patients (64.3%). Nine patients were H1069Q homozygous. Eighteen patients were H1069Q compound heterozygous, two of them had H1069Q/P969Q and one patient H1069Q/3400delC genotype. In two of the 15 H1069Q-negative patients a novel mutation in exon 13 (T977M) was detected. One H1069Q-negative patient had a mutation in exon 8 (G710S). None of the studied mutations was detected in 12 WD patients. H1069Q-positive patients from various European countries had the same haplotype pattern. The H1069Q point mutation is frequent in Hungarian patients with WD and appears to have originated from a single founder in Eastern Europe. In contrast, mutations in exons 8, 13, 15, and 18 are uncommon in Hungarian WD patients., (Copyright 2002 Wiley-Liss, Inc.)
- Published
- 2002
- Full Text
- View/download PDF
72. Distribution of patients with Wilson disease carrying the H1069Q mutation in Austria.
- Author
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Cauza E, Ulrich-Pur H, Polli C, Gangl A, and Ferenci P
- Subjects
- Amino Acid Substitution, Austria epidemiology, Emigration and Immigration, Europe, Eastern epidemiology, Exons, Female, Humans, Male, Population Surveillance, Prevalence, Surveys and Questionnaires, Hepatolenticular Degeneration epidemiology, Hepatolenticular Degeneration genetics, Histidine genetics, Mutation
- Abstract
Background/aims: More than 100 different mutations of the Wilson disease (WD) gene have been reported so far, but only the H1069Q mutation is frequently found in patients of North and East European origin. We wanted to know if there is a connection between the migration pattern in Central Europe and the geographical distribution of this mutation in Austria., Methods: One hundred and nine patients (91 index patients and 18 asymptomatic siblings) with WD diagnosed in Austria were included in this study. Eighty-one of the 91 index patients were born in Austria. Evaluation criteria included the place of birth of each member of the study group, as well as of his parents and grandparents., Results: Out of the 81 index patients born in Austria, 72 were tested for the H1069Q mutation. Twelve (16.7%) were homozygous carriers of the H1069Q mutation, 29 (40.3%) were compound heterozygous and 31 (43.0%) had an unknown mutation on both chromosomes. Eight of the twelve H1069Q homozygotes were born close to the northeastern border of Austria (neighboring the Czech Republic, Slovakia and Hungary). Compound heterozygous patients showed a more variable geographical distribution with respect to their birthplace. The patients with unknown mutation were scattered all over Austria., Conclusion: These data provide further evidence that the H1069Q mutation originates from Eastern Europe. In patients from these countries the PCR-based testing for this mutation may be useful for differential diagnosis and family studies.
- Published
- 2000
73. The impact of apolipoprotein E genotypes on age at onset of symptoms and phenotypic expression in Wilson's disease.
- Author
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Schiefermeier M, Kollegger H, Madl C, Polli C, Oder W, Kühn H, Berr F, and Ferenci P
- Subjects
- Adolescent, Adult, Age of Onset, Apolipoprotein E2, Apolipoprotein E3, Apolipoprotein E4, Cholesterol, LDL genetics, Female, Genotype, Homozygote, Humans, Male, Mutation, Phenotype, Apolipoproteins E genetics, Hepatolenticular Degeneration genetics
- Abstract
Wilson's disease is a disorder of biliary copper excretion that may result in severe neurological symptoms and advanced liver disease. The wide variation of phenotypic disease expression cannot be fully explained by the different mutations of the Wilson disease gene. In neurological disorders, such as Alzheimer's disease, temporal lobe epilepsy and cerebral trauma, the presence of the apolipoprotein E (ApoE) allele epsilon4 is associated with an increased vulnerability of the brain to the effects of the disease, whereas the presence of the ApoE genotype epsilon3/3 appears to provide moderate neuroprotection. We examined whether this hypothesis holds true for the development of neurological symptoms in patients with Wilson's disease. The ApoE genotype and the H1069Q mutation (the most common in Wilson's disease) status were determined by polymerase chain reaction-based mutation assays in 121 well-characterized, symptomatic index patients with Wilson's disease. An investigation profile was established in which the patients were grouped according to the clinical symptoms at presentation, the ApoE genotypes and the status of the H1069Q mutation. Fifty-nine per cent of the 121 patients had the allele combination ApoE epsilon3/3 (21% ApoE epsilon3/4, 19% ApoE epsilon3/2, 1% ApoE epsilon4/2). The distribution of ApoE genotypes did not deviate from known distributions in healthy European subjects. Within the group of 40 H1069Q-homozygous patients, the onset of symptoms was significantly delayed in patients with the ApoE epsilon3/3 genotype (25 +/- 6 years at presentation) compared with patients with the ApoE epsilon3/4 genotype (20 +/- 3 years at presentation). In this study, the ApoE genotype was established as an important factor delaying the onset of neurological and hepatic symptoms, but not modifying phenotypic disease expression in a homogeneous group of patients with Wilson's disease (all H1069Q-homozygotes, similar genetic background). The presence of ApoE epsilon3/3 attenuates clinical manifestations in Wilson's disease by mechanisms which might involve the antioxidant and membrane-stabilizing properties of the ApoE 3 protein.
- Published
- 2000
- Full Text
- View/download PDF
74. The relation of iron status and hemochromatosis gene mutations in patients with chronic hepatitis C.
- Author
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Kazemi-Shirazi L, Datz C, Maier-Dobersberger T, Kaserer K, Hackl F, Polli C, Steindl PE, Penner E, and Ferenci P
- Subjects
- Adolescent, Adult, Aged, Austria, Female, Gene Frequency, Hemochromatosis complications, Hepatitis C, Chronic complications, Hepatitis C, Chronic enzymology, Hepatitis C, Chronic pathology, Homozygote, Humans, Iron Overload complications, Iron Overload metabolism, Liver enzymology, Liver metabolism, Liver pathology, Male, Middle Aged, Mutation, Missense, Polymerase Chain Reaction, Hemochromatosis genetics, Hepatitis C, Chronic metabolism, Iron metabolism
- Abstract
Background & Aims: Elevated hepatic iron concentration may affect the response to antiviral therapy in chronic hepatitis C. This study explored the contribution of genetic hemochromatosis to iron accumulation in chronic hepatitis C., Methods: HFE mutations (C282Y and H63D) were assessed in 184 patients with chronic hepatitis C virus and 487 controls. Liver biopsy specimens were available in 149 patients. Hepatic iron content was measured in 114 patients by atom-absorption spectrophotometry., Results: The C282Y and H63D allele frequencies were 7.06 and 11.6 in patients and 4.83 and 11.09 in controls, respectively. Eight patients were homozygotes (5 C282Y [2.7%] and 3 H63D [1.6%]), 2 compound heterozygotes (1%), and 49 heterozygotes (14 C282Y [7.6%] and 35 H63D [19%]). Biochemical evidence of iron overload was more common in patients with HFE mutations (28 of 47) than in those without (34 of 102; P = 0.0045). Histological iron grading and hepatic iron content overlapped among patients with or without mutations. A hepatic iron index of >1.9 was observed only in 1 of the 4 C282Y homozygotes and 1 of the 3 H63D homozygotes., Conclusions: HFE mutations contribute to but do not fully explain hepatic iron accumulation in chronic hepatitis C. Furthermore, C282Y or H63D homozygosity in chronic hepatitis C is not necessarily associated with a high hepatic iron content.
- Published
- 1999
- Full Text
- View/download PDF
75. Detection of the His1069Gln mutation in Wilson disease by rapid polymerase chain reaction.
- Author
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Maier-Dobersberger T, Ferenci P, Polli C, Balać P, Dienes HP, Kaserer K, Datz C, Vogel W, and Gangl A
- Subjects
- Adolescent, Adult, Austria, Female, Genetic Linkage, Hepatolenticular Degeneration diagnosis, Hepatolenticular Degeneration pathology, Heterozygote, Homozygote, Humans, Liver pathology, Male, Pedigree, Hepatolenticular Degeneration genetics, Point Mutation, Polymerase Chain Reaction methods
- Abstract
Background: Most known mutations in the gene associated with Wilson disease are rare. Only the His1069Gln mutation is found often in patients of Northern or Eastern European origin., Objective: To examine the frequency of the His1069Gln mutation in Austrian patients with Wilson disease and their families by using a new, rapid polymerase chain reaction (PCR) test., Design: Cross-sectional study., Setting: University medical center., Patients: 83 patients from 72 families and 98 relatives of 11 homozygous index patients., Measurements: Results of a semi-nested PCR-based assay to detect the His1069Gln mutation in Wilson disease, clinical symptoms, and liver histologic findings., Results: 20 patients, including 5 siblings, were homozygous for the His1069Gln mutation. Thirty-three patients, including 4 siblings, were compound heterozygotes. The mutation was not detected in 30 patients, including 2 siblings. Homozygotes were older at onset of symptoms (mean age, 24 +/- 6 years) than compound heterozygotes (17 +/- 6 years [95% CI, 3.3 to 10.7 years]; P = 0.0135) and patients with other mutations (18 +/- 8 years [CI, 1.8 to 10.2 years]; P = 0.117). Homozygotes were more often female (73.3%) than were compound heterozygotes (48% [CI, 0.94% to 2.46%]) and patients with other mutations (50% [CI, 0.91% to 2.37%]) (P = 0.05). Four of 98 asymptomatic relatives of 11 homozygous index patients were also homozygotes. Heterozygosity was confirmed in 46 relatives (19 parents, 11 children, and 16 distant relatives)., Conclusion: The His1069Gln mutation was detected in 61% of Austrian patients with Wilson disease. Polymerase chain reaction may be useful for diagnosis and screening of family members of homozygous index patients, even if first-degree relatives are not available for examination.
- Published
- 1997
- Full Text
- View/download PDF
76. [ON THE INCIDENCE OF KETONE REDUCTASES IN MICROORGANISMS].
- Author
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POLLI C, DIEKMANN H, KIS Z, and ETTLINGER L
- Subjects
- Incidence, Alcohol Oxidoreductases, Mucor, Oxidoreductases
- Published
- 1965
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