Biomedical subjects

M Artini

Publications and source records attributed to M Artini.

At least 19 recordsLinked to original sources

PubMed2004

Presence of the ica operon in clinical isolates of Staphylococcus epidermidis and its role in biofilm production.

Staphylococcus epidermidis is an important cause of catheter-associated infections, which are attributed to its ability to form a multilayered biofilm on polymeric surfaces. This ability depends, in part, on the activity of the icaADBC locus and the icaR gene, which are involved in the production of the polysaccharide intercellular adhesin (PIA) that is functionally necessary for cell-to-cell adhesion and biofilm accumulation. The present study determined: (1) the prevalence of the icaADBC operon in S. epidermidis isolates from catheter-related and other nosocomial infections; (2) the correlation between the presence of this operon, biofilm production and resistance to antibiotics; (3) the expression of ica genes and biofilm production; and (4) the genetic relatedness of the isolates. The results showed that icaRADBC was present in 45% of the isolates included in the study, and that such isolates were significantly more resistant to the main antibiotics tested than were ica-negative isolates. The presence of the entire cluster did not always correlate with biofilm production, determined under different culture conditions, but there was evidence to suggest a correlation when at least two genes (icaAD) were co-transcribed. Eight of 18 ica-positive isolates had the entire operon in the same restriction fragment after pulsed-field gel electrophoresis, but the isolates were not clonal. Estimation of genetic relatedness indicated that ica-positive S. epidermidis isolates belonged to different lineages, distributed in only one of two major clusters, with a genetic distance of c. 0.12.

Bacterial Adhesion↗

PubMed2002

Prevalence and genomic variability of transfusion transmitted virus in Italian cryptogenic chronic liver disease and healthy blood donors.

BACKGROUND: Infection with transfusion transmitted virus, a new member of the Parvoviridae family, has been found in patients both with chronic and fulminant post-transfusion cryptogenic hepatitis. AIM: To evaluate the prevalence and clinical impact of transfusion transmitted virus infection in Italy. PATIENTS AND METHODS: Studies were carried out on 256 patients and control subjects from three centres from Northern, Central and Southern Italy (92 nonA-nonC chronic hepatitis, 10 acute non fulminant cryptogenic hepatitis, 41 hepatitis C virus-related chronic hepatitis and 113 blood donors). Serum transfusion transmitted virus was detected by nested polymerase chain reaction using two overlapping sets of primers. RESULTS: A total of 52 of the 92 patients (54.3%) with chronic cryptogenic liver disease and 17 of the 41 hepatitis C virus chronic hepatitis patients (41.4%) were transfusion transmitted virus-DNA positive. Transfusion transmitted virus co-infection in hepatitis C virus patients was not associated with either a higher severity of liver histology or higher alanine transaminase levels or signs of cholestasis, transfusion transmitted virus was found in 48 out of 113 (42.4%) blood donors. In the majority of samples, transfusion transmitted virus DNA was detected with only one of the two sets of primers used. Genotyping and phylogenetic analysis performed on 21 randomly selected viral isolates showed the presence of both type 1 and type 2 transfusion transmitted virus and allowed identification of two isolates with high homology to genotype 6, described, so far, mostly in Japan. CONCLUSIONS: Transfusion transmitted virus type 1 and 2 infection is common among blood donors and patients with liver disease in Italy. The pathogenic potential of transfusion transmitted virus type 1 and 2 in nonA-nonC hepatitis patients is unlikely but further studies are needed to evaluate the epidemiological and clinical impact of other transfusion transmitted virus subtypes.

Adolescent↗

PubMed2001

Immunotherapy with interferon-alpha in patients affected by chronic hepatitis C induces an intercorrelated stimulation of the cytokine network and an increase in depressive and anxiety symptoms.

Immunotherapy with interferon-alpha (IFNalpha) may induce depressive symptoms, anxiety and major depression when administered for at least 1-3 months at a dose of 3-10 MUI daily, twice or three times a week. Previously, it has been shown that immunotherapy with interleukin-2 (IL-2) significantly induces the cytokine network, as measured by increases in serum IL-6, IL-10 and the IL-2 receptor (IL-2R), and that the immunotherapy-induced changes in the cytokine network are significantly correlated with the increases in depression ratings. The main aim of this study was to examine the effects of immunotherapy with IFNalpha on the cytokine network in relation to changes in depression and anxiety ratings. Fourteen patients, affected by chronic active C-hepatitis, were treated with IFNalpha (3-6 MUI s.c. three/six times a week for 6 months) and had measurements of serum IFN-gamma (IFNgamma), IL-2, IL-6, IL-6R, IL-8 and IL-10 before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFNalpha. Severity of depression and anxiety were measured with the Montgomery-Asberg Depression Rating Scale (MADRS) and the Hamilton Anxiety Rating Scale (HAM-A), respectively. Repeated measure (RM) design ANOVAs showed significantly higher MADRS and HAM-A scores 2-4 weeks and 4-6 months after starting IFNalpha-based immunotherapy than at baseline. RM design ANOVAs showed significantly higher serum IL-6 and IL-8 levels 2-4 weeks after starting IFNalpha-based immunotherapy and higher serum IL-10 levels 2-4 weeks and 4-6 months after starting therapy than at baseline. There were significant relationships between the IFNalpha-induced changes in serum IL-6 or IL-8 and the depression and anxiety scores. The findings show that IFNalpha-based immunotherapy induces the cytokine network and that IFNalpha-induced increases in IL-6 predicts the development of depressive symptoms. Depressive symptoms following IFNalpha treatment may be secondary to cytokine induction, including that of IL-6.

Adult↗

PubMed2001

Hepatitis C virus (HCV) RNA determination after two weeks of induction interferon treatment is an accurate predictor of nonresponse: comparison of two treatment schedules.

The aim of this study was to analyze of HCV kinetics during interferon treatment administered daily or three times weekly. Seventy-seven naive patients were randomized to two treatment courses starting with four weeks of high-dose interferon administered daily or three times weekly. Twenty-two patients (28.6%) achieved end-of-treatment response and nine (11.7%, four of whom received daily induction) sustained response. The initial decline of viral load was sharper in patients receiving daily induction, but the rates of early RNA clearance were independent of treatment schedule, being higher in patients with genotype non-1. Detectable HCV RNA during treatment predicted nonresponse more significantly than high pretreatment viral load or genotype 1. HCV RNA at week 2 was the best predictor (100% sensitivity in patients receiving daily induction). In conclusion, daily induction increased the HCV decline slope, but not the rate of virological response. HCV RNA at week 2 reliably identified nonresponders.

Alanine Transaminase↗

PubMed2001

Treatment with interferon-alpha (IFN alpha) of hepatitis C patients induces lower serum dipeptidyl peptidase IV activity, which is related to IFN alpha-induced depressive and anxiety symptoms and immune activation.

We have shown that treatment with interleukin-2 (IL-2) or interferon-alpha (IFN alpha) may induce depressive symptoms and activation of the cytokine network and that IL-2 treatment may diminish serum dipeptidyl pepdidase IV (DPP IV) activity. DPP IV (EC 3.4.14.5) is a membrane bound serine protease which catalyzes the cleavage of some cytokines and neuroactive peptides which modulate T cell activity. The aims of the present study were to examine the effects of IFN alpha-based immunotherapy on serum DPP IV activity in relation to induction of the inflammatory response system. In 18 patients with chronic active hepatitis C, we determined the Montgomery and Asberg Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HAM-A), serum DPP IV activity, the kynurenine/tryptophan (K/T) quotient, which is an indicator of cytokine (in particular IFN)-induced catabolism of tryptophan, and serum interleukin-8 (IL-8) before starting therapy and 2, 4, 16 and 24 weeks after immunotherapy with IFN alpha. IFN alpha-immunotherapy significantly suppressed serum DPP IV 2--4 weeks and 16--24 weeks after starting IFN alpha-based immunotherapy. The reduction in serum DPP IV activity was more pronounced 16--24 weeks after starting immunotherapy than after 2--4 weeks. The IFN alpha-induced suppression of serum DPP IV activity was significantly correlated to IFN alpha-induced increases in the MADRS and HAM-A and increases in the K/T quotient and serum IL-8. In conclusion, long-term immunotherapy with IFN alpha suppresses serum DPP IV activity and the immunotherapy-induced changes in DPP IV are related to increases in severity of depression, anxiety and activation of the inflammatory response system.

Adult↗

PubMed1999

Presence of effector CD8+ T cells in hepatitis C virus-exposed healthy seronegative donors.

CTL responses against multiple hepatitis C virus (HCV) epitopes were detected in 7 of 29 (24.1%) healthy family members (HFM) persistently exposed to chronically HCV-infected patients (HCV-HFM). These precursor CTL were at very low or undetectable frequencies, as determined by limiting dilution analysis. However, when HCV-specific effector CD8+ T cells, freshly isolated from PBMC of HCV-HFM, were assessed by a sensitive enzyme-linked immunospot assay, their frequencies were severalfold higher than those of precursor CTL. These results indicate that the two assays detect two functionally distinct T cell populations and that the effector cells are not assayed by the 51Cr-release assay. Furthermore, the combination of cell depletion and enzyme-linked immunospot analyses showed that the effector cells were confined into a CD8+ CD45RO+ CD28- population. The persistence of effector CD8+ T cells specific for both the structural and nonstructural viral proteins in uninfected HCV-HFM, suggest that: 1) an immunological memory is established upon a subclinical infection without any evidence of hepatitis, in a large cohort of HCV-exposed individuals; 2) because these cells required neither restimulation nor the addition of particular cytokines in vitro for differentiating in effectors, they should be capable of prompt HCV-specific effector function in vivo, possibly providing antiviral protection; and 3) the maintenance of effector T cell responses may be sustained by persisting low-level stimulation induced by inapparent infections.

Adolescent↗

PubMed1999

Nonsteroidal anti-inflammatory drug metabolism potentiates interferon alfa signaling by increasing STAT1 phosphorylation.

A sustained response to standard interferon therapy for chronic hepatitis C has been demonstrated in no more than 25% of patients. To improve interferon alfa (IFN-alpha) antiviral effect, a number of combination therapies with IFNs plus other drugs have been proposed for both relapser and nonresponder hepatitis C virus (HCV)-infected patients. Although the causes of IFN resistance in subsets of HCV-infected patients are unknown, both viral and host factors have been involved, including defects in IFN signal transduction and IFN-alpha/beta receptor down-regulation. Here, we report that nonsteroidal anti-inflammatory drugs (NSAIDs), which have been proposed for IFN-alpha combination therapy in nonresponders, potentiate IFN-alpha signaling. We found that, in the hepatoma cell lines, CCL13/Chang and HepG2, indomethacin, a selective cyclo-oxygenase 1 and 2 (COX-1 and COX-2) inhibitor, increases IFN-alpha stimulation of interferon-stimulated response element (ISRE)-dependent transcription in a dose-dependent manner. Interestingly, maximal potentiation was observed with suboptimal IFN-alpha concentrations. Indomethacin exerts its effects by synergizing with IFN-alpha in inducing STAT1 activation by phosphorylation, without affecting concurrent Jak1 phosphorylation. Our data indicate that blockade of arachidonic acid (AA) metabolism by indomethacin activates a signaling pathway that converges on STAT1 activation to potentiate IFN-alpha-dependent gene activation.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed1999

Long-term response to interferon alpha is unrelated to "interferon sensitivity determining region" variability in patients with chronic hepatitis C virus-1b infection.

BACKGROUND/AIMS: Contradictory data have been reported about the predictive value of the variability in interferon sensitivity determining region (ISDR) of hepatitis C virus (HCV) genotype-1b on response to interferon-alpha (IFN-alpha) therapy. The aim of this study was to examine this issue in a series of patients with long-term response to IFN treatment. METHODS: We retrospectively analyzed 24 patients with chronic HCV genotype-1b infection treated with IFN-alpha (total dose median 677, range 216-1350 MU) selected in 6 Italian Liver Units. These patients were defined as true long-term responders (LTR) since they showed persisting biochemical and virological responses to IFN treatment (mean follow-up 38 months). HCV genomes from pretreatment serum samples were amplified and directly sequenced. The ISDR amino-acid sequences obtained were aligned and compared with the published sequence of HCV-J. RESULTS: Amino-acid substitutions were found in 23 of the 24 patients, and 22 of them showed an H to R amino-acid change at codon 2218. Fourteen patients showed only one mutation (at codon 2218), two had 2, five had 3, one had 4 and one had 5 mutations. When we compared the ISDR sequences from the 24 LTR with those of non-responders (NR), we found no significant correlation between the number of mutations and the response to therapy. CONCLUSIONS: Our results demonstrate that the persisting efficacy of IFN treatment in patients with chronic HCV is not related to the number of ISDR amino acid substitutions of the infecting viruses. Further studies are needed to verify whether other NS5A sequences outside the ISDR might be involved in the mechanisms of IFN resistance.

Adult↗

PubMed1999

Viral and host factors in determining response of relapsers with chronic hepatitis C to retreatment with interferon.

In chronic hepatitis C the rate of relapse after an end-of-treatment response to interferon may exceed 50%. The usefulness of retreatment of relapsers with interferon in obtaining a complete sustained response and the role of clinical, virological and immunological features in determining long-term efficacy of retreatment are unclear. We aimed to assess the efficacy of interferon retreatment in obtaining a complete sustained response, to evaluate whether increasing the dose may enhance responsiveness, and to identify possible predictors of sustained response. We enrolled 42 patients with biopsy-proven chronic hepatitis C without cirrhosis who had previously responded to a six-month course of Interferon-alpha2b (total dose: group A, 22 patients, 234 MU; group B, 20 patients, 468 MU) and then relapsed. All, except one, were HCV-RNA negative at the end of first cycle of interferon; most (31/42, 74%) were infected by HCV 1b. Subjects were randomly allocated to receive another cycle of interferon either at the original dose (group A1: 234 MU, 11 patients; group B1 468 MU, 10 patient) or twice the original dose (group A2: 468 MU, 11 patients; group B2: 936 MU, 10 patients). At the end of the second cycle of interferon, 24 subjects (57%) had normal ALT and were HCV-RNA negative, and 16 (39%) had normal ALT, but were HCV-RNA positive. A complete sustained response was obtained in eight patients (19%), at a similar rate in all treatment groups. Complete sustained responders were different from the other patients in terms of age (35.9 +/- 10.4 vs 44.1 +/- 8.8, P = 0.027), rate of infection with non-1b HCV (6/8 vs 5/34, P = 0.0005), serum HCV-RNA (74,016 vs 321,428 median copies/ml, P = 0.037) and serum levels of 90K/MAC-2 BP (5.76 +/- 3.01 vs 10.25 +/- 5.16 units/ml, P = 0.02), an N-glycoprotein implicated in cellular defense functions. Multivariate logistic analysis validated age and HCV genotype as independent predictors of CSR. Among noncirrhotic relapsers who received a total interferon dose > or = 234 MU in the first cycle, retreatment usually induced end-of-treatment response. A complete sustained response was obtained in only one of every five subjects. Increasing the dose of interferon above that of the first cycle did not enhance the rate of sustained response. In conclusion we might assert that young subjects infected by non-1b HCV and with low levels of HCV-RNA and of 90K/MAC-2 BP are the best candidates for retreatment.

Adult↗

PubMed1999

Chronic cryptogenic hepatitis in childhood is unrelated to hepatitis G virus.

OBJECTIVES: The aim of this study was to define the features of chronic cryptogenic hepatitis (CCH) in childhood and to investigate whether it is related to hepatitis G virus infection. METHODS: Forty-six children (24 males; age range, 1.5 to 17 years) with CCH were studied. CCH was diagnosed when serum alanine aminotransferase concentrations were more than 1.5 times normal for longer than 6 months without any apparent cause of liver disease. RESULTS: No patient had acute symptomatic onset or had received a blood transfusion. Three had undergone minor surgical procedures. All appeared to be healthy during follow-up (median, 4.2 years; range, 1 to 10 years). Hypertransaminasemia was the only aberrant liver function test. Elevated serum alanine aminotransferase values alternated with normal values in 40 children (86.9%). Five children (10.8%) had a spontaneous sustained (>12 months) remission of hypertransaminasemia. Twelve (26%) had laboratory signs of autoimmunity, but none fulfilled the criteria for autoimmune hepatitis. Of 20 children who underwent liver biopsy, 13 (65%) had minimal chronic hepatitis, 4 (20%) had mild chronic hepatitis and 3 (15%) had moderate chronic hepatitis. Serum hepatitis G virus RNA was detected in 2 girls (4%) whose risk factor was a hepatitis G virus-infected mother and a minor surgical procedure, respectively. In 12 families at least 1 other member had chronic liver disease. CONCLUSIONS: Childhood CCH seems to be a symptomless disease characterized by isolated hypertransaminasemia with onset during the first 4 years of life and mild to moderate histologic liver lesions. Although the frequency of spontaneous remissions is low, childhood CCH seems, in the short run, to be a nonprogressive disease. Hepatitis G virus does not play a major role in CCH.

Adolescent↗

PubMed1998

Expression of co-stimulatory molecules by Kupffer cells in chronic hepatitis of hepatitis C virus etiology.

In this paper we show that in viral hepatitis most Kupffer cells (KCs) are activated and express high levels of CD80, CD40, and class-II MHC molecules, thus acquiring the phenotype of professional antigen presenting cells (APCs). Activated KCs display a close contact with CD4+ T lymphocytes and form KCs-T lymphocyte clusters. Clusters are found within the sinusoids, across the sinusoid wall, and within the liver parenchyma as well, as a consequence of transendothelial migration (TEM). The positivity of activated KCs for hepatitis C virus (HCV) antigens, which likely reflects phagocytosis of infected hepatocytes, suggests that KCs-T cell clusters represent the morphological expression of the functional interaction between KCs acting as professional APCs and antigen-experienced CD4+ T lymphocytes within the liver. These phenotypic and morphological changes are distinct features of livers in chronic hepatitis patients compared with controls.

Adult↗

PubMed1998

Extranodal lymphomas associated with hepatitis C virus infection.

Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma. We describe eight cases of B-cell extranodal non-Hodgkin's lymphoma occurring during the course of chronic HCV-related hepatic disease (low-grade of mucosa-associated lymphoid tissue [MALT]-type; diffuse large cell; Burkitt; diffuse small cell). Some were localized to the liver (2), liver and spleen (1), spleen (1), peritoneal cavity (1), parotid gland (1); others manifested in the nasopharynx (1) and eyelid (1) but were accompanied by nodal disease. Four lymphomatous specimens available for molecular analysis exhibited clonal immunoglobulin gene rearrangements, lacked bcl-2, bcl-6, c-myc genes and p53 alterations, and did not contain replicative intermediate HCV RNA, as documented by a strand-specific reverse transcriptase-polymerase chain reaction. Low levels of positive-strand HCV RNA were detected in a single hepatic lymphoma, suggesting the presence of the virus in residual hepatocytes. The antigen-driven properties of HCV-associated B-cell malignant neoplasms may be considered for hepatic MALT-type lymphoma, which probably originated from lymphoid tissue acquired during long-standing HCV infection.

Adult↗

PubMed1997

Primary effusion Burkitt's lymphoma with t(8;22) in a patient with hepatitis C virus-related cirrhosis.

Hepatitis C virus (HCV) infection may be complicated by non-Hodgkin's lymphoma through yet unknown pathogenetic mechanisms. We describe the case of a patient with HCV-related cirrhosis who developed a primary effusion lymphoma (PEL) of Burkitt's type confined to the peritoneal cavity, in the absence of immunodeficiency or autoimmunity. Paracentesis followed by immunophenotyping, karyotyping, and molecular studies allowed us to diagnose a small noncleaved B-cell lymphoma (CD20+, CD24+, CD10+, CD5-, CD23-, lambda+) with the t(8;22) (q24;q11) translocation and clonal rearrangement of the immunoglobulin heavy chain gene. HCV-RNA, Epstein-Barr virus and Kaposi's sarcoma-associated herpesvirus were not identified within lymphoma cells. The finding of HCV-RNA in the ascitic fluid suggests a link between HCV and development of lymphoma with HCV playing the role of persistent antigenic stimulation to intraperitoneal B-cell clonal expansion(s).

Ascitic Fluid↗

PubMed1996

Long-lasting memory T cell responses following self-limited acute hepatitis B.

The molecular and cellular basis of long-term T cell memory against viral antigens is still largely undefined. To characterize anti-viral protection by memory T cells against non-cytopathic viruses able to cause acute self-limited and chronic infections, such as the hepatitis B virus (HBV), we studied HLA class II restricted responses against HBV structural antigens in 17 patients with acute hepatitis B, during the acute stage of infection and 2.2 to 13 yr after clinical resolution of disease. Results indicate that: (a) significant T cell proliferative responses to HBV nucleocapsid antigens were detectable in all patients during the acute phase of infection and in 14/17 also 2-13 yr after clinical resolution of disease; b) long-lasting T cell responses were sustained by CD45RO+T cells, predominantly expressing the phenotype of recently activated cells; c) limiting dilution analysis showed that in some patients the frequency of HBV-specific T cells was comparable to that observed in the acute stage of infection and, usually, higher than in patients with chronic HBV infection; d) the same amino acid sequences were recognized by T cells in the acute and recovery phases of infection; and e) HBV-DNA was detectable by nested-PCR in approximately half of the subjects. to conclusion, our results show that vigorous anti-viral T cell responses are detectable in vitro several years after clinical recovery from acute hepatitis B. Detection of minute amounts of virus in some recovered subjects suggests that long-term maintenance of an active anti-viral T cell response could be important not only for protection against reinfection but also for keeping the persisting virus under tight control.

Acute Disease↗

PubMed1996

Elevated serum levels of 90K/MAC-2 BP predict unresponsiveness to alpha-interferon therapy in chronic HCV hepatitis patients.

BACKGROUND: The clinical outcome of hepatitis virus infections is though to depend on the complex interplay between the host immune response profile and virus factors. 90K/MAC-2 BP is a novel member of the Scavenger Receptor Cysteine Rich protein superfamily that functions as a molecular alarm signal for the cellular immune system against both cancer cells and virus infections. METHODS: To assess the significance and the potential clinical usefulness of testing for serum levels of 90K/MAC-2 BP in chronic viral hepatitis patients we studied 115 consecutive patients with chronic HCV hepatitis, 28 HBsAg chronic hepatitis patients, 12 asymptomatic HCV carriers and 11 asymptomatic HBV carriers. 103 out of the 115 HCV patients have been treated with recombinant alpha 2a-interferon at the dose of 3 Mega Units (MU) t.i.w. for 6 months followed by 1.5 MU t.i.w. for 6 months, and have been followed up for a further 12 months. Serum levels of 90K/MAC-2 BP were measured by an immunoradiometric assay based on the specific SP-2 monoclonal antibody. RESULTS AND CONCLUSIONS: Serum 90K/MAC-2 BP levels are increased in chronic viral hepatitis patients, being significantly higher in HCV than in HBV patients. In chronic HCV hepatitis, serum 90K/MAC-2 BP levels are related to both the degree of disease severity and duration of infection. Moreover, elevated 90K/MAC-2 BP serum levels are an independent predictor of failure to respond to alpha-interferon treatment in a cohort of community-acquired chronic hepatitis C patients.

Adult↗

PubMed1996

Hepatitis B virus pX activates NF-kappa B-dependent transcription through a Raf-independent pathway.

In this study, we characterized the molecular events involved in the activation of the ubiquitous transcription factor NF-kappa B by the viral transactivator pX. pX expression in HeLa cells determines a manyfold increase in NF-kappa B-dependent transcription, which is associated with an increase in p50/p65 heterodimer DNA-binding activity. Since the I kappa B-alpha inhibitory subunit proteolytic degradation, which follows its phosphorylation/modification, is a key event in NF-kappa B activation by different stimuli (such as growth factors, phorbol esters, tumor necrosis factor, UV irradiation, and oxygen radicals), we investigated pX effects on I kappa B-alpha, as well as the possible involvement of known signalling pathways in pX-induced NF-kappa B-dependent transcription. We observed that although pX had no direct effect on p50 or p65, it was able to restore the I kappa B-alpha-suppressed p50/p65 activity. More directly, the stable expression of pX in HeLa cells resulted in reduced levels of I kappa B-alpha in the cytoplasm. Pretreatment of the cells with H7, calphostin C, tyrphostin 25, or N-acetylcysteine did not impair the effects of pX on NF-kappa B, thus ruling out the involvement of protein kinase C, tyrosine kinases, and oxygen radicals. Finally, while most of the known NF-kappa B-activating agents converge on Raf-1 protein kinase, when Raf-1 activity is blocked by overexpression of a dominant negative mutant, the effects of pX on NF-kappa B are not impaired. Thus, we suggest that although pX is able to activate the Ras/Raf-1-signalling pathway, it triggers NF-kappa B activation by an as yet unidentified Raf-1-independent pathway.

Base Sequence↗

PubMed1995

Infection of circulating and liver infiltrating T cells by hepatitis C virus of different subtypes.

Hepatitis C virus (HCV) infection display a very high rate of progression to chronicity and, like many other viruses causing persistent infections, it displays a tropism for the cells of the immune system. Peripheral blood mononuclear cells (PBMCs) from 21 HCV chronic carriers and long-term T cell clones derived from circulating or liver infiltrating T lymphocytes were tested by cDNA "nested" PCR for positive and negative strand HCV-RNA. The presence of HCV genomes in PBMCs is a frequent, although not constant, finding and can be accompanied by active viral replication, as suggested by the coexistence of negative strand HCV-RNA. Infected T cells are more represented in livers than in periphery, as indicated by comparing HCV-RNA detection in T cell clones isolated from both the compartments. Sequencing of viral genomes present in PBMCs and liver infiltrating lymphocytes showed that all the three major HCV genotypes present in our population of chronic carriers can infect lymphoid cells. Although each clonal population of T cells is infected by a single strain of HCV, in the same patient lymphoid cells can harbor different viral populations, different from those circulating at that moment in the serum.

Adult↗

PubMed1995

Distribution of three major hepatitis C virus genotypes in Italy. A multicentre study of 495 patients with chronic hepatitis C.

Different genotypes of hepatitis C virus (HCV) have been shown to have distinct geographical distribution and to associate with variable clinical features. To evaluate their role in chronic hepatitis in Italian patients, we studied 495 consecutive cases with chronic hepatitis C seen in nine sentinel centres homogeneously distributed over Italy. HCV genotyping was carried out using a dot-blot hybridization assay with genotype-specific probes. Four hundred and eleven patients were viraemic and could be evaluated: 57% were found to be infected with HCV-1, 31% with HCV-2, 8% with HCV-3, 1% showed mixed infection and 3% were ascribed to HCV-2b or HCV-4 by direct sequencing. Geographical distribution showed discrete territorial variations. A history of drug addiction was commoner in patients infected with HCV-3. There were no significant differences in activity of liver disease among different HCV genotypes but the response to interferon therapy was reduced in patients infected with HCV-1 compared to HCV-2 or HCV-3.

Adult↗