[Hepatitis A. An eradicable disease?].
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Biomedical subjects
Publications and source records attributed to R Esteban.
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Most yeast strains carry a cytoplasmic double-stranded RNA (dsRNA) molecule called W, of 2.5 kb in size. We have cloned and sequenced most of W genome (1), and we proposed that W (+) strands were identical to 20S RNA, a single-stranded RNA (ssRNA) species, whose copy number is highly induced under stress conditions. Recently it was proposed that 20S RNA was circular (2). In this paper, however, we demonstrate that both W dsRNA and 20S RNA are linear. Linearity of W dsRNA is shown by the stoichiometric labelling of both strands of W with 32P-pCp and T4 RNA ligase. The last 3' end nucleotide of both strands is about 70 to 80% C and 20 to 30% A. Linearity of 20S RNA is directly demonstrated by a site-specific cleavage of 20S RNA with RNase H, using an oligodeoxynucleotide complementary to an internal site of 20S RNA. The cleavage produced not one but two RNA fragments expected from the linearity of 20S RNA.
Some strains of the yeast Saccharomyces cerevisiae harbor a double-stranded RNA (dsRNA) molecule, called T. We obtained T cDNA clones by random priming of denatured T dsRNA followed by reverse transcription. Sequence data of T show that only one strand ((+)-strand) has coding capacity for a protein with 940 amino acids which spans almost the entire length of the molecule (2.9 kilobases). Within this protein we found a sequence pattern characteristic of RNA-dependent RNA polymerases of (+)-strand and double-stranded RNA viruses. Although T has no homology with other dsRNAs found in S. cerevisiae, such as L-A, L-BC, M1, or W, the T-encoded protein shows a high degree of conservation with the W-encoded protein. This conservation extends beyond a region that contains the consensus sequences for RNA-dependent RNA polymerases, suggesting that both T and W are evolutionarily related. With a (+)-strand-specific probe for T we identified 23 S RNA, a new single-stranded RNA (ssRNA) species with a sedimentation coefficient of 23 S. T and 23 S RNA have the same mobility under denaturing conditions with glyoxal, suggesting that 23 S RNA is, in fact, the (+)-single-stranded RNA form of T dsRNA. 23 S RNA synthesis is induced under stress conditions such as heat shock and starvation. The relationship between T and 23 S RNA clearly resembles the one between W and its single-stranded derivative form, 20 S RNA. Thus T and W dsRNAs (and their respective single-stranded species) constitute a new RNA family in S. cerevisiae.
To assess the efficacy of interferon-alpha in acute hepatitis C, 28 patients with acute posttransfusion hepatitis were randomized to receive 3 million units of recombinant interferon-alpha three times weekly for 12 wk or no treatment. Biochemical, histological and serological parameters were monitored during 1 yr of follow-up. Serum ALT levels were normal at the end of therapy in 73% of treated patients and only in 38% of control patients (p = 0.06); these differences disappeared at 6 and 12 mo of follow-up. Anti-hepatitis C virus seroconversion occurred later and at a lower rate in the group of patients who received interferon-alpha. Treated patients had a trend toward less severe hepatic lesions with lower histological activity as compared with the control group, but no statistical differences were observed. No severe side effects of interferon-alpha were detected during the study. In summary, a 3-mo course of interferon-alpha in acute hepatitis C is safe and might have some effect in diminishing disease activity only during the treatment period; however, and probably because of a small sample size, no benefit of interferon-alpha in the long-term outcome of this disease was demonstrated.
Of 30,231 donors tested, 368 (1.2%) were anti-HCV positive. Of these, 254 have been evaluated, with the following results: only 25% have a history of parenteral risk, seroprevalence increases with age and approximately 80% of those that are anti-HCV positive in our population are probably infected with HCV. In addition, an unexpectedly large number of these persons have chronic and/or severe liver disease and will require combined diagnostic approaches for accurate evaluation.
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Sequencing of multiple recombinant clones generated from polymerase chain reaction-amplified products demonstrated that the degree of heterogeneity of two well-conserved regions of the hepatitis C virus (HCV) genome within individual plasma samples from a single patient was consistent with a quasispecies structure of HCV genomic RNA. About half of circulating RNA molecules were identical, while the remaining consisted of a spectrum of mutants differing from each other in one to four nucleotides. Mutant sequence diversity ranged from silent mutations to appearance of in-frame stop codons and included both conservative and nonconservative amino acid substitutions. From the relative proportion of essentially defective sequences, we estimated that most circulating particles should contain defective genomes. These observations might have important implications in the physiopathology of HCV infection and underline the need for a population-based approach when one is analyzing HCV genomes.
Although the efficacy of hepatitis B vaccines in patients under chronic hemodialysis treatment has been well documented, the persistence of immunity in this population remains largely unknown. In this study we have followed 60 hemodialysis patients up to 3 years after primary hepatitis B vaccination (four doses of recombinant hepatitis B vaccine; Engerix B, 20 mg/dose) to evaluate the persistence of immunity (as indicated by serum levels of antibody to hepatitis B surface antigen-anti-HBs-higher than or equal to 10 mIU/ml). Fourty-four (73%) patients developed anti-HBs levels above 10 mIU/ml after vaccination; the remaining 16 (27%) vaccinees were considered nonresponders and were given a booster dose that again failed to elicit an immunoresponse. After 3 years of follow-up, 18 out of 44 (41%) responders had no detectable anti-HBs levels in the serum (antibody loss occurring within 8 and 12 months in 3 cases, within 1 and 2 years in 13, and within 2 and 3 years in 2 other cases). When compared with the responders that lost their antibodies during the follow-up period, those who remained immunoreactive 3 years after vaccination was initiated were younger and had higher anti-HBs levels at 8 months of follow-up. Two hepatitis B virus infections were detected among nonresponders during the follow-up period. Based on these data, we conclude that patients undergoing chronic hemodialysis therapy not only have lower response rates to hepatitis B vaccination than healthy adults, but also that these are frequently transient.(ABSTRACT TRUNCATED AT 250 WORDS)
The clinical case of a 56 year old patient who developed a grafted hepatic tumoration on a year after diagnosis of liver cirrhosis of alcoholic etiology is reported. Diagnosis of the mass was made by fine needle aspiration punction ecographically guided obtaining a cellular block which, upon anatomopathological study, revealed the presence of a malignant mesenchymal tumor; a leiomyosarcoma. Not only is this type of primary hepatic tumor rare but its appearance on a liver of alcoholic cirrhosis is also of interest. It is much more common to find primary hepatic tumors of epithelial origin, concretely hepatocarcinomas. The value of this finding is discussed with the importance of the ecographically guided punction enabling the establishment of a precise histological diagnosis being underlined. The prognosis of malignant hepatic mesenchymal tumors is commented upon as well as the long survival associated to the same, which, in this case, was longer than 18 months.
Most strains of the yeast Saccharomyces cerevisiae harbor a double-stranded RNA (dsRNA) molecule, called W. We obtained W cDNA clones by random priming of denatured W dsRNA followed by reverse transcription. Sequence data of W shows that only one strand ((+)-strand) has coding capacity for a protein with 829 amino acids which spans almost the entire length of the molecule (2.5 kilobases). Within this protein we found a sequence pattern characteristic of RNA dependent RNA polymerases of (+)-strand and double-stranded RNA viruses. W has no homology with other dsRNAs found in S. cerevisiae, such as L-A, L-BC or M1. However, a (+)-strand-specific probe for W hybridized with 20-S RNA. Furthermore, W (+)-strands comigrated with 20 S RNA in strand separation gels. These results suggest that 20 S RNA is a (+)-single-stranded RNA form of W dsRNA itself or a closely related molecule.
Separation of 7-8 S and 19 S forms of serum IgM antibodies to the hepatitis delta virus by rate-zonal centrifugation was carried out on serum from 24 patients with hepatitis delta virus infection: 4 patients with acute, self-limited hepatitis; 5 patients with hepatitis delta virus superinfection progressing to chronicity; and 15 patients with chronic hepatitis delta virus. The high molecular weight IgM form (19 S) was predominantly detected in acute hepatitis delta virus cases, whereas the low molecular weight (7 S) form was found in chronic hepatitis delta virus cases. The serological profile of these two forms of IgM antibody to hepatitis delta virus was investigated in serial samples from five patients with acute hepatitis delta virus superinfection that evolved to chronic hepatitis delta virus. We found that, in the acute stage of the disease, the 19 S form was predominant, whereas 6 mo later a predominance of 7-8 S IgM was observed. These results suggest that IgM antibody to hepatitis delta virus antibody forms are different in acute and chronic hepatitis delta virus infection and that their detection only helps in differentiating an acute infection from a chronic infection but not a hepatitis delta virus-hepatitis B virus-HBV coinfection from hepatitis delta virus superinfection in the acute stage of the disease.
Four cases with Obstructive Sleep Apnoea Syndrome (OSAS) are presented. They consisted of two cases with TMJ ankylosis with micrognathia, one case with Treacher Collins Syndrome, and one case with the Long Face Syndrome. Standard and specific cephalometric parameters were obtained to detect the site of the obstruction. Polysomnographic studies yielded information regarding the patient's sleep-wake state, respiratory and cardiac functioning, pre- and post-operatively. A temporary tracheostomy corrected the symptoms in one patient but the syndrome recurred when it was closed. Surgical correction of the maxillofacial anomalies will re-establish normal sleep patterns preventing OSAS.
To determine whether the abnormalities of cell-mediated immunity described in chronic D hepatitis are associated with hepatitis D virus (HDV) infection or concomitant human immunodeficiency virus (HIV) infection, serologic and tissue hepatitis B virus (HBV) and HDV markers and T lymphocyte subsets were studied in serum samples from 38 patients with chronic D hepatitis, 26 of whom had HIV infection. Patients with chronic D hepatitis and HIV infection had significantly lower peripheral blood T4:T8 ratios resulting from a significant increase in T8+ (suppressor/cytotoxic) cells, while numbers of T lymphocyte subsets were normal in cases with chronic D hepatitis only. HIV+ patients showed an increase in HBV replication (identified by hepatitis B core antigen in liver and hepatitis B e antigen and HBV DNA in serum) and in HDV replication (tissue D antigen and HDV RNA) without evidence of more active liver disease. Probably the immunologic disturbances detected in chronic D hepatitis are secondary to HIV infection, do not contribute to the pathogenesis of liver injury, and are associated with increased viral B and D replication.
The sensitivity and specificity of two non-radioactive spot hybridization assays for hepatitis B virus DNA (HBV-DNA) using biotin and digoxygenin-labelled DNA probes were investigated in parallel in 122 serum samples from patients with chronic hepatitis B and 50 controls. The results were compared with an isotopic technique using a 32P-labelled probe. HBV-DNA was detected in 56 (80%) out of 70 hepatitis B "e" antigen (HBeAg)-positive cases and in 4 (8%) out of 52 antibody to hepatitis B "e" antigen (anti-HBe)-positive cases using the digoxygenin or 32P-labelled probes. No false positives were found with either method. Using the biotin-labelled probe, 16% of sera gave discordant results, which were considered to be false positive. The time required for detection of serum HBV-DNA was 2 hours for the non-radioactive probes and 16 hours for the isotopic probes. This study suggests that the digoxygenin-labelled probe for detection of HBV-DNA is the most rapid and sensitive method for routine diagnosis of viral replication in clinical laboratories.
Familial amyloid polyneuropathy type 1 or Corino Andrade's disease (FAP 1) is classified amongst the hereditary systemic amyloidosis, being autosomically dominant and preferably affecting the peripheral nervous system. Our country is the fourth world focus with regard to incidence, preceded only by Portugal, Japan, and Sweden. Amyloid involvement is rare, generally following primary forms. There are only three cases described of these hereditary forms, none of which is of the FAP type 1. Our goal is to present a patient diagnosed of FAP type 1 who developed hemoptysis during the course of her disease, observing an amyloid bronchial infiltrate in the samples obtained by bronchoscopy. This is the first case described of pulmonary involvement in this type of amyloidosis according to the literature reviewed.
232 asymptomatic HBsAg carriers were controlled between May/1986 and May/1990. The were detected in our blood bank between 1974 and 1976 or during pregnancy or delivery period after 1981. 23 of 232 (10%) became negative during the follow-up, this happening more frequently in carriers after 5 years of follow-up. Only 2 of 209 carriers with HBsAg were HBeAg positive and 1 of these was also DNA-VHB positive. None of the HBeAg negative carriers showed DNA-VHB; only 5 had increased transaminases. 7 were anti-VHC positive, these individuals experiencing more frequent increases in transaminases. The results of this study suggests that the determination of transaminases, viral activity markers, anti-HD, anti-VHC in HBsAg carriers are enough to identify those with hepatic disease.
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