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Biomedical subjects

R Bertoni

Publications and source records attributed to R Bertoni.

At least 19 recordsLinked to original sources
PubMed2002

FISH mapping of 18S-28S and 5S ribosomal DNA, (GATA)n and (TTAGGG)n telomeric repeats in the periwinkle Melarhaphe neritoides (Prosobranchia, Gastropoda, Caenogastropoda).

Spermatocyte chromosomes of Melarhaphe neritoides (Mollusca, Prosobranchia, Caenogastropoda) were studied using fluorescent in situ hybridization (FISH) with four repetitive DNA probes (18S rDNA, 5S rDNA, (TTAGGG)n and (GATA)n). Single-colour FISH consistently mapped one chromosome pair per spread using either 18S or 5S rDNA as probes. The telomeric sequence (TTAGGG)n hybridized with termini of all chromosomes whereas the (GATA)n probe did not label any areas. Simultaneous 18S-5S rDNA and 18S-(TTAGGG)n FISH demonstrated that repeated units of the three multicopy families are closely associated on the same chromosome pair.

Animals↗
PubMed1999

Conserved hepatitis C virus sequences are highly immunogenic for CD4(+) T cells: implications for vaccine development.

The HLA class II-restricted T-cell response to hepatitis C virus (HCV) antigens is believed to influence the final outcome of hepatitis C, because it is vigorous in patients who recover from acute hepatitis C, but it is weak in those who develop a chronic infection. For this reason, exogenous stimulation of T-cell responses in chronic HCV infection may represent a strategy to cure patients with chronic hepatitis C by approximating the vigor of their T-cell reactivity to that of patients who succeed in recovering from hepatitis. It may also be a preventive approach to avoid spread of the virus by facilitating the development of a vigorous protective response at the very early stages of infection. T-cell-based vaccines composed of immunodominant, promiscuous, and conserved T-cell epitopes may represent a powerful tool to achieve optimal stimulation of the T-cell reactivity. To identify HLA class II-restricted T-cell epitopes useful for this purpose, 22 subjects with acute HCV infection were studied and followed for an average time of 29 months. Eight of them recovered from hepatitis, and 14 developed a chronic infection. Overlapping 20-mer peptides covering the entire core and NS4 antigens and a panel of peptides representing highly conserved regions of core, NS3, NS4, and NS5 were used. By direct peripheral blood T-cell stimulation and by fine-specificity analysis of HCV-specific T-cell lines and clones, highly immunogenic T-cell epitopes were identified within core, NS3, and NS4. All these epitopes are immunodominant and highly conserved among the known HCV isolates. Moreover, they are promiscuous, because they can be presented to T cells by different HLA class II molecules. Immunodominance, sequence conservation, and promiscuity make these epitopes ideal components of preventive or therapeutic T-cell-based vaccines against HCV.

Acute Disease↗
PubMed1998

Human class I supertypes and CTL repertoires extend to chimpanzees.

Using an in vitro peptide stimulation strategy, two chimpanzees that were acutely infected by the hepatitis B virus (HBV) produced peripheral blood CTL responses to several HBV-encoded epitopes that are known to be recognized by class I-restricted CTL in acutely infected humans. One animal responded to three HBV peptides that, in humans, are restricted by HLA-A2; the other animal responded to three peptides that are restricted by HLA-B35 and HLA-B51, members of the HLA-B7 supertype in man. The peptides recognized by each chimp corresponded with the ability of its class I molecules to bind peptides containing the HLA-A2 and HLA-B7 supermotifs. Similar, apparently class I-restricted CTL responses to some of these peptides were also detected in occasional HBV-uninfected chimps. These results demonstrate that the CTL repertoire overlaps in humans and chimps and that the HLA-A2 and HLA-B7 supertypes extend to the chimpanzee. Based on these results, the immunogenicity and efficacy of vaccines designed to induce CTL responses to human HLA-restricted viral epitopes may be testable in chimpanzees.

Amino Acid Sequence↗
PubMed1998

Antiviral cell-mediated immune responses during hepatitis B and hepatitis C virus infections.

Cell-mediated immune responses to hepatitis B (HBV) and hepatitis C virus (HCV) antigens are vigorous and multispecific in acute, self-limited infections. Moreover, the prevalent cytokine pattern of circulating virus-specific T cells from patients who recover spontaneously from acute hepatitis is Th1-like. Longitudinal analysis of the T cell response to HCV antigens from the early stages of HCV infection in patients who recover from hepatitis and those who do not indicates that weaker responses and a prevalent Th2 pattern of cytokine production is associated with viral persistence and chronic evolution of disease. Although similar sequential studies are missing in hepatitis B, the observation that HBV-specific T cell responses are very weak or totally undetectable in the peripheral blood of patients with long-lasting chronic hepatitis B suggests that strength and quality of virus-specific T cell responses at the early stages of infection may influence the final outcome of both hepatitis B and C. While T cell hyporesponsiveness seems to be an important determinant for HBV persistence once chronic hepatitis has developed, this mechanism appears to be less critical in chronic HCV infection, because the vigor and quality of HCV-specific T cell responses seem to improve as a function of the duration of infection. This is shown by the finding that HCV-specific CD4- and CD8-mediated responses are easily detectable in the peripheral blood of patients with long-lasting chronic hepatitis C and that production of Th1 cytokines predominates within their livers. HCV therefore seems to be able to persist even in the face of an active T cell response and to acquire the capacity to survive within a host environment apparently unfavorable to its persistence. The high variability of HCV may explain its efficiency in escaping immune surveillance.

Hepatitis B↗
PubMed1997

Human histocompatibility leukocyte antigen-binding supermotifs predict broadly cross-reactive cytotoxic T lymphocyte responses in patients with acute hepatitis.

The present study was designed to determine if highly conserved hepatitis B virus (HBV)-derived peptides that bind multiple HLA class I alleles with high affinity are recognized as cytotoxic T lymphocyte (CTL) epitopes in acutely infected patients. Peripheral blood mononuclear cells from 67 patients with acute hepatitis B, and 12 patients convalescent from acute hepatitis B, were stimulated with three panels of peptides, each of which bind with high affinity to several class I alleles from the HLA-A2-, HLA-A3-, or HLA-B7-supertypes. In these patients, 8 of the 19 peptides tested were found to represent CTL epitopes recognized by two or more alleles in each supertype. Two sets of nested peptides were recognized in the context of alleles with completely unrelated peptide binding specificities. Finally, promiscuous recognition by the same CTL of a given peptide presented by target cells expressing different A2 subtypes was also commonly observed. In conclusion, several HBV-specific CTL epitopes, recognized by acutely infected or convalescent patients in the context of a wide range of HLA alleles have been identified. These results demonstrate the functional relevance of the supertype grouping of HLA class I molecules in a human viral disease setting. Furthermore, they represent a significant advance in the development of a totally synthetic vaccine to terminate chronic HBV infection and support the feasibility of a systematic approach to development of similar vaccines for prevention and treatment of other chronic viral infections.

Acute Disease↗
PubMed1997

Effects of interferon treatment on the antiviral T-cell response in hepatitis C virus genotype 1b- and genotype 2c-infected patients.

The viral genotype may influence the response to interferon (IFN) treatment in chronic hepatitis C virus (HCV) infection. To characterize potential mechanisms responsible for this effect, we assessed whether IFN modulation of HCV-specific T-cell responses differs in patients infected by different genotypes. The T-cell response to HCV core protein was sequentially analyzed before and during IFN treatment in two groups of patients chronically infected with HCV genotype 1b (eight patients) or 2c (eight patients). Overlapping 20 mer peptides corresponding to the amino acid sequence of the prevalent viral population identified in the serum of each patient were used for the analysis of the T-cell proliferative response to avoid possible problems caused by amino acid differences between infecting virus and HCV proteins used in vitro. Recombinant HCV core antigen was used in parallel. The level of viremia was monitored by competitive polymerase chain reaction (PCR). The T-cell response to HCV peptides and recombinant core protein detected throughout the follow-up was significantly more vigorous in genotype 2c- than in genotype 1b-infected patients. This difference was the result of a greater enhancement of the T-cell response caused by IFN treatment in genotype 2c- compared with genotype 1b-infected patients. The different IFN modulatory effect on T cells from genotype 1b- and genotype 2c-infected patients illustrates an aspect of the virus-host interaction, which may contribute toward the explanation of why different genotypes differ in responsiveness to IFN treatment.

Adult↗
PubMed1996

Different clinical behaviors of acute hepatitis C virus infection are associated with different vigor of the anti-viral cell-mediated immune response.

The anti-viral T cell response is believed to play a central role in the pathogenesis of hepatitis C virus infection. Since chronic evolution occurs in > 50% of HCV infections, the sequential analysis of the T cell response from the early clinical stages of disease may contribute to define the features of the T cell response associated with recovery or chronic viral persistence. For this purpose, 21 subjects with acute hepatitis C virus infection were sequentially followed for an average time of 44 wk. Twelve patients normalized transaminase values that remained normal throughout the follow-up period; all but two cleared hepatitis C virus-RNA from serum. The remaining nine patients showed persistent viremia and elevated transaminases. Analysis of the peripheral blood T cell proliferative response to core, E1, E2, NS3, NS4, and NS5 recombinant antigens and synthetic peptides showed that responses to all hepatitis C virus antigens, except E1, were significantly more vigorous and more frequently detectable in patients who normalized transaminase levels than in those who did not. By sequential evaluation of the T cell response, a difference between the two groups of patients was already detectable at the very early stages of acute infection and then maintained throughout the follow-up period. The results suggest that the vigor of the T cell response during the early stages of infection may be a critical determinant of disease resolution and control of infection.

Acute Disease↗
PubMed1984

Comparison of the effects of polyglycolic acid and monofilament nylon sutures in the common bile duct of pigs.

The tissue reaction and involvement of cells in the common bile duct of young pigs after surgery with two suture materials, polyglycolic acid and monofilament nylon, have been described. By comparing the different tissue reactions to the suture materials the authors observe that the use of non-absorbable polymer sutures and their long lasting presence in living tissues, may interfere with the healing process, since the sutures tend to migrate within the common duct wall and be expelled into the lumen owing perhaps to the delayed immuno-allergic reaction which develops in the common duct wall. In contrast polyglycolic acid seems to be biologically well tolerated and well integrated as a suture material, which is reabsorbed with the help of cell enzymes producing a complete restitutio ad integrum of the wall.

Animals↗