Infection of B cells with hepatitis C virus for the development of lymphoproliferative disorders in patients with chronic hepatitis C
ABSTRACT Infection with hepatitis C virus (HCV) is associated with lymphoproliferative disorders, represented by essential mixed cryoglobulinemia and B-cell non-Hodgkin's lymphoma, but the pathogenic mechanism remains obscure. HCV may infect B cells or interact with their cell surface receptors, and induce lymphoproliferation. The influence of HCV infection of B cells on the development of lymphoproliferative disorders was evaluated in 75 patients with persistent HCV infection. HCV infection was more prevalent (63% vs. 16%, 14%, or 17% P < 0.05 for each), and HCV RNA levels were higher (3.35 +/- 3.85 vs. 1.75 +/- 2.52, 2.15 +/- 2.94 or 2.10 +/- 2.90 log copies/100 ng, P < 0.01 for each) in B cells than CD4(+), CD8(+) T cells or other cells. Negative-strand HCV RNA, as a marker of viral replication, was detected in B cells from four of the 75 (5%) patients. Markers for lymphoproliferative disorders were more frequent in the 50 patients with chronic hepatitis C than the 32 with chronic hepatitis B, including cryoglobulinemia (26% vs. 0%, P < 0.001), low CH(50) levels (48% vs. 3%, P = 0.012), and the clonality of B cells (12% vs. 0%, P < 0.01). By multivariate analysis, HCV RNA in B cells was an independent factor associated with the presence of at least one marker for lymphoproliferation (odds ratio: 1.98 [95% confidence interval: 1.36-7.24], P = 0.027). Based on the results obtained, the infection of B cells with HCV would play an important role in the development of lymphoproliferative disorders.
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ABSTRACT: Our recent study indicated that peripheral B cells in chronic hepatitis C (CHC) patients were infected with hepatitis C virus (HCV). It was also demonstrated that the frequency of CD27(+) B cells, i.e. memory phenotype, was significantly reduced in the peripheral blood of CHC patients. An assumption was made by these findings that the CD27(+) B cells are susceptible to apoptosis when infected with HCV. Therefore, in this study, the susceptibility of CD27(+) B cells to apoptosis in CHC patients was analyzed. Contrary to our assumption, it was found that CD27(+) B cells are more resistant to apoptosis than the counterpart subset, i.e. CD27(-) B cells. The rationale for this finding is discussed with regard to the possible role for memory B cells as an HCV reservoir for persistent infection in CHC patients.Virus Research 09/2010; 155(1):349-51. DOI:10.1016/j.virusres.2010.09.017 · 2.83 Impact Factor
Conference Paper: Inherent DCM operation of the asymmetrical interleaved dual buck-boost[Show abstract] [Hide abstract]
ABSTRACT: A fifth order DC/DC converter based on the asymmetric connection of two buck-boost cells with complementary activation of their switches is presented. In steady state, the new converter inherently operates in discontinuous conduction mode (DCM). With a duty cycle greater than 38%, the asymmetrical interleaved dual buck-boost (AIDBB) behaves like an inverting boost converter. The AIDBB exhibits some benefits of interleaving cells without the need for specific control strategies to distribute the input current between the buck-boost cells. Mainly, the converter input current and output voltage ripples are significantly smaller than their average values. Due to the DCM operation, the system presents three operation intervals whose duration is independent of the converter parameters.IECON 02 [Industrial Electronics Society, IEEE 2002 28th Annual Conference of the]; 12/2002
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ABSTRACT: Over the past 2 decades considerable evidence has accumulated on the association between hepatitis C virus (HCV) and hepatitis B virus (HBV) and several hematologic malignancies, most notably B-cell non-Hodgkin lymphoma (NHL). In this review we summarize this evidence, address possible mechanisms whereby hepatitis viruses may contribute to lymphomagenesis, and discuss the therapeutic fallouts from this knowledge. Most of this evidence is on HCV, and this is the main focus of the review. Moreover, we mainly address the association with NHL, the most prevalent hematologic malignancy, and the most extensively investigated with regard to an association with hepatitis viruses. Available evidence on the association with other hematologic malignancies is also addressed briefly.Blood 10/2010; 117(6):1792-8. DOI:10.1182/blood-2010-06-275818 · 10.43 Impact Factor