Impact of Blood Pressure Variability on Cardiac and Cerebrovascular Complications in Hypertension

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Mutagenesis of hepatitis C virus E1 protein affects its membrane-permeabilizing activity

The E1 glycoprotein of hepatitis C virus is a transmembrane glycoprotein with a C-terminal anchor domain. When expressed inEscherichia coli, E1 induces a change in membrane permeability that is toxic to the bacterial cell. The C-terminal hydrophobic region (aa 331–383) of E1 is mainly responsible for membrane association and for inducing changes in membrane permeability. These observed changes are similar to those produced inE. coliby influenza virus M2, human immunodeficiency virus gp41 and poliovirus 3AB proteins, whose hydrophobic domains are thought to cause pore formation in biological membranes. To further characterize the activity of E1 at a molecular level, the membrane-permeabilizing ability of a second internal hydrophobic region (aa 262–291) was examined by expressing different deletion mutants of E1 in anE. colisystem that is widely used for analysing membrane-active proteins from other animal viruses. Moreover, highly conserved amino acids in the C-terminal hydrophobic region were mutated to identify residues that are critical for inducing changes in membrane permeability. Analysis of cell growth curves of recombinant cultures and membrane-permeability assays revealed that synthesis of this fragment increased the flux of small compounds through the membrane and caused progressive cell lysis, suggesting that this domain has membrane-active properties. Furthermore, analysis of C-terminal mutants indicated that the conserved amino acids Arg339, Trp368and Lys370play a critical role in protein function, as both cell lysis and changes in membrane permeability induced by the wild-type clone could be blocked by substitutions in these positions

Modulation of RANTES expression by HCV core protein in liver derived cell lines

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus (HCV) infection is associated with high percentage of chronicity which implies the ability of the virus to evade or modulate host cell immune system. Modulation of chemokines, such as RANTES may be part of the virus induced pathogenicity. We examined the effect of core and structural proteins of HCV on RANTES expression in two liver derived cell lines, HepG2 and Chang Liver (CHL).</p> <p>Methods</p> <p>HepG2 and Chang Liver (CHL) cell lines were established and selected for constitutive expression of HCV core and structural genes. Flow cytometry and quantitative RT-PCR analysis were performed to examine the effect of HCV core protein on RANTES expression. Luciferase analysis after RANTES-Luc-promoter transfection of established cell lines was assayed by luminometer measurements (RLU) of RANTES promoter activity. IRF-1 and IRF-7 expression was then examined by immunoblotting analysis.</p> <p>Results</p> <p>Results of flow cytometry and RT-PCR analysis indicated that RANTES is differentially regulated by HCV core protein in the two cell lines examined as its expression was inhibited in HepG2 cells, by a reduction of RANTES promoter activity. Conversely, RANTES protein and mRNA were induced by the core protein in CHL cells, through the induction of the promoter.</p> <p>Since HCV genome modulates IRF-1 and IRF-7 in replicon system and IRF-1, IRF-3 and IRF-7 have been reported to regulate RANTES promoter in various cell systems, analysis of the mechanism underlying RANTES modulation by the core protein revealed that IRF-1 expression was induced in HepG2 cells by the core protein, whereas in CHL cells it was expressed at a very low level that was not influenced by transfection with the core protein construct. This suggested that IRF-1 level may mediate the expression of RANTES in cell lines of liver origin. The effect of the core protein on RANTES promoter was countered by co-transfection with NF90, a double-stranded-RNA binding protein that activates some interferon response genes and acts as a component of cell defense against viral infection.</p> <p>Conclusion</p> <p>HCV core protein have opposite effects on the expression of RANTES in different cell types <it>in vitro</it>, possibly reflecting a similar scenario in different microenvironments <it>in vivo</it>.</p

Un criterio di determinazione delle condizioni di credibilita' di effetto Domino tra impianti soggetti a rischio di incidente rilevante in uno stabilimento industriale complesso

Consiglio Nazionale delle Ricerche - Biblioteca Centrale - P.le Aldo Moro, 7, Rome / CNR - Consiglio Nazionale delle RichercheSIGLEITItal

Neoadjuvant chemotherapy for Non-Small-Cell lung cancer: Does it really impact on postoperative outcome after lung resection?

BACKGROUND Although some studies seem to indicate a positive prognostic value of induction chemotherapy in patients with locally advanced Non-Small-Cell Lung Cancer (NSCLC), its impact on postoperative mortality and morbidity is not well established. MATERIALS AND METHODS We reviewed the records of 83 consecutive patients who underwent thoracotomy after induction therapy between 1996 and 2007 (Group 1). Results were compared to those of a control group of 166 patients surgically treated in the same period without prior neoadjuvant therapy (Group 2). RESULTS The two groups were matched for age, sex, histology, comorbidity, respiratory function, and surgical procedure. There was no hospital mortality. Cumulative incidence of major complications was 32% in Group 1 and 37% in Group 2 (p=0.18). The incidence of each complication considered did not significantly differ between the two groups. A higher percentage of patients in Group 1 required blood transfusions (21.7% vs 4.2%, p&lt;0.0001). Multiple logistic regression analysis showed forced expiratory volume in 1 s (FEV1)&lt;75% of predicted (p=0.018) and blood transfusions (p=0.006) to be independent risk factors for major postoperative events in Group 1. DISCUSSION Preoperative chemotherapy did not seem to affect overall morbidity and mortality. Patients with a FEV1B75% of predicted or requiring blood transfusions resulted at increased risk of developing major complications

eComment. Surgery for isolated adrenal metastasis from non-small-cell lung cancer: the role of preoperative PET/CT scan"

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