169,872 research outputs found
Different levels of variability in subtypes 1b and 4a of hepatitis C viruses
No full textWe performed genetic and phenic analyses to evaluate nucleotide and amino-acid sequences of the amino-terminus of the E1 protein of HCV genotype 1b (extracted from databank) and 4a (characterised in this study). The non-synonymous (ka) mutation analysis demonstrated that the genome of genotype 1b was not saturated by variations, with a rate of transition/transversion (s/v) of 1.5, which is similar to the expected ratio (i.e., 2.0). The s/v ratio in genotype 4a isolates was lower (0.98), indicating saturation due long-term variability. Moreover, the genotype 1b sequences showed a higher number of ka mutations (s+v) (mean of 2.8 per sequence) than genotype 4a (mean of 1.5). The introduction of ka mutations resulted in a higher degree of amino acid variability in genotype 4a. In the genome of genotype 1b, each nucleotide mutation introduced new amino acids, with a Granthan distance of 3.35-42.5, whereas for genotype 4a the distances ranged from 48.8 to 102.1. The phenic analysis also indicated different and complex patterns of amino-acid substitution. Finally, diverse isoelectric points and hydrophobicity were predicted for the two genotypes, with a higher acidity for genotype 4a E1 proteins
Pattern of recurrence and survival of c-Ia NSCLC diagnosed by transpleural methods
No full textAim. The aim of this study was to evaluate if transpleural diagnostic methods as percutaneous fineneedle aspiration biopsy (FNAB) or tumour wedge resection by video-assisted thoracoscopic surgery (VATS) impact on local recurrence and long term survival of patients affected by non-small cell lung cancer (NSCLC). Methods. Records concerning 179 patients with peripheral c-Ia NSCLC who underwent complete resection from 1994 to 2000 have been reviewed. Patients were randomized into two groups according to the diagnostic method employed, as follows: in group I (N.=63) diagnosis was obtained by bronchoscopy; in group II (N.=116) diagnosis was obtained by FNAB (N.=59) or tumour wedge resection by VATS (N.=57) after a negative bronchoscopy. Survival curves were compared using log-rank test. Distribution of frequencies was analyzed with Chi-square and Fisher's exact test. Results. The two groups of patients did not significantly differ in terms of age, gender, forced expiratory volume in 1 second, comorbidities, histological type and tumour size; pathologic stage IIb was more frequent in group I. At a median follow-up of 48 months, (range 2-108 months), local recurrence was found in 9.5% (N.=6) of the patients in group I and in 12.5% (N.=15) of patients in group II (P=NS); distant metastasis were found in 28.6% (N.=18) of patients in group I and in 13.8% (N.=16) in group II (P=0.03). Patients in group II had a statistically better five-year survival rate than patients in group I (70% and 55% respectively P=0.016). Conclusion. FNAB and tumour wedge resection by VATS represent valuable diagnostic methods for lung cancers, since they do not seem to increase the risk of local recurrence. On the other hand, tumours diagnosed by bronchoscopy have a worse prognosis, that may be related to their higher metastatic potential rather than to diagnostic procedure itself
Molecular epidemiology of hepatitis C virus genotype 4 isolates in Egypt and analysis of the variability of envelope proteins E1 and E2 in patients with chronic hepatitis
No full textWe analyzed hepatitis C virus (HCV) genotype 4 isolates circulating in the Alexandria District (Egypt) in terms of genetic divergence and the presence of different subtypes. Hypervariable region 1 (HVR1) and the NH2 region of the E2 protein were characterized, and the heterogeneity of subtype 4a isolates was evaluated by analyzing epitope frequencies, immunoproteasome prediction, and possible glycosylation patterns. The heterogeneity of the nucleotide sequences was greater than that found in previous studies, which reported only subtype 4a. Subtype 4a was most common (78% of cases), yet four new subtypes were found, with subtype 4m representing 11% of the cases and the other three subtypes representing another 11%. Substantial heterogeneity was also found when the intrasubtype 4a sequences were analyzed. Differences in the probability of glycosylation and in the positions of the different sites were also observed. The analysis of the predicted cytotoxic T-lymphocyte epitopes showed differences in both the potential proteosome cleavage and the prediction score. The Egyptian isolates in our study also showed high variability in terms of the HVR1 neutralization epitope. Five of these isolates showed amino acid substitutions never previously observed (a total of six positions). Four of these residues (in four different isolates) were in positions involved in anchoring to the E2 glycoprotein core and in maintaining the HVR1 conformation. The results of this study indicate that HCV genotype 4 in Egypt is extremely variable, not only in terms of sequence, but also in terms of functional and immunological determinants. These data should be taken into account in planning the development of vaccine trials in Egypt
Viral determinants and host immune responses in the pathogenesis of HBV infection
No full textHepatitis B virus (HBV) is a virus that infects about 350,000,000 people worldwide with a clinical spectrum of acute hepatitis, the healthy carrier state, cirrhosis and hepatocellular carcinoma (HCC). The outcome of HBV infection is the result of complicated viral-host interactions. As in other infections with non-cythopatic viruses, the immune response is thought to play a crucial role in disease pathogenesis but there is increasing evidence that a variety of viral mechanisms, some depending on the function of virally encoded proteins, have a profound impact on the infected hepatocytes, the liver microenvironment, and host anti-viral responses. Indeed, the virus has evolved multiple mechanisms to ensure its success in infecting a susceptible host. The essential aspects of the life cycle of HBV and the host immune response are reviewed and recent new developments in the molecular virology of HBV, including experimental animal models, in the role of accessory viral proteins in disease pathogenesis and HCC development and in the characterisation of the T cell response in the control of HBV infection, are highlighted. (C) 2002 Wiley-Liss, Inc
Hepatitis C virus infection in Italian kidney graft recipients. Changing risk factors and hepatitis C virus genotypes
No full textThe risk for hepatitis C virus infection in kidney transplant recipients has been reduced by the introduction of accurate diagnostic tests. Little is known, however, of the current risk factors and the molecular genetics of hepatitis C virus infection in Italy
GB virus C/hepatitis G virus exposure in Italian pediatric and young adult thalassemic patients
No full textRelationship between virological evolution and acute exacerbation of chronic hepatitis C (A-E-CHC) and during the natural history of infection
No full textLung cancer with chest wall involvement: Predictive factors of long-term survival after surgical resection
No full textMultimodal management of lung cancer extending to chest wall and type of surgical procedure to be performed are still debated. The aim of this retrospective analysis was to analyze the predictive factors of long-term survival after surgery, focusing on depth of infiltration, type of surgical intervention and possible role of preoperative therapies, comparing survival of these patients with that of a group of patients affected by a Pancoast tumour and surgical treated in the same period. Materials and methods: We reviewed records of 83 consecutive patients with NSCLC in stage T3 (owing to direct extension to chest wall), who underwent surgical resection in our Thoracic Surgery Unit between January 1994 and December 2003. Patients were classified in two groups: pancoast tumours (PT) or chest wall extending tumours (CW): survival and prognostic factors of each category were analyzed. Results: In the CW group we had 68 patients: 45 were in stage IIB (pT3N0), 23 in stage IIIA (pT3-N1-2). Histology revealed adenocarcinoma in 23 cases, squamous cell carcinoma in 34, large cells anaplastic carcinoma in 8, adenosquamous carcinoma in 3. An involvement of chest wall tissues beyond the endothoracic fascia was found in 21 patients, while in the remaining 47 the invasion of chest wall tissues was confined to the parietal pleura. An extrapleural dissection was performed in 48 patients while combined pulmonary and chest wall en bloc resection was required in 20 patients. Resection was incomplete in three cases. In the PT group we had 15 patients: 11 were in stage IIB and 4 in stage IIIA. Histological type was adenocarcinoma in 10 cases, squamous cell carcinoma in 4 and adenosquamous carcinoma in 1. A univariate analysis performed in the CW group showed that survival was significantly affected by nodal status, stage, extension of chest wall invasion, type of lung resection and residual disease. In a multivariate analysis we found that nodal status, completeness of resection and extension of chest wall involvement maintained a significant prognostic value. There was no difference between the survival curve of CW and PT group: considering the two subset of CW patients, on the basis of depth of infiltration, survival of PT patients was significantly better than that of CW patients with involvement of muscular tissues and ribs (p = 0.02). Conclusion: Nodal status, radical resection and depth of chest wall infiltration are the main predictive factors affecting long-term survival, while surgical procedure does not impact on it if margins of resection are free from disease. The better survival observed in PT patients let us to hypothesize that an induction chemo-radiation therapy, as routinely administered to PT patients, could have a potential benefit in survival of patients with CW tumour extending beyond parietal pleura. © 2006 Elsevier Ireland Ltd. All rights reserved
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