Publications by authors named "Houghton M"

This pilot study was designed to establish the effect of long term alpha interferon treatment in haemophilia patients with chronic hepatitis C. Overall, three of eight (37.5%) patients showed a complete response, three of eight (37.

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We have noticed that suboptimal specimen processing and storage conditions may cause false-negative results in the detection of hepatitis C virus (HCV) RNA in plasma or serum. To establish the influence of specimen handling in a serological laboratory on the rate of detection of HCV RNA by the cDNA polymerase chain reaction (cDNA-PCR), we tested routine serum samples and fresh-frozen plasma samples from the same bleeding from confirmed anti-HCV-positive blood donors. When primers from the NS3/NS4 region were used, HCV RNA was detected in fresh-frozen plasma from 67% of the donors, whereas positive results were obtained with only 50% of the serum samples that had been subjected to routine serological procedures.

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Hepatitis C virus (HCV) is a distant relative of pestiviruses and flaviviruses, but it has a 5' untranslated region (UTR) with some features structurally similar to that of picornaviruses. In order to test the role of the 5' UTR in controlling the expression of the HCV polyprotein, we fused full-length or deleted versions of the 5' UTR of HCV-1 RNA to chloramphenicol acetyl transferase (CAT) mRNA to monitor CAT activity in vivo. We found: (1) the full-length 5' UTR of HCV-1 RNA is translationally inactive while 5' deletions which mimic a 5' subgenomic RNA detected in vivo are active, (2) an efficient cis-acting element which represses translation is found at the 5' terminus, (3) a putative element which enhances translation is found near the 3' terminus of the 5' UTR, (4) additional cis-acting elements including small open reading frames (ORFs) upstream from the putative enhancer element downregulate translation.

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Hepatitis C virus (HCV) is a major cause of post-transfusion and sporadic hepatitis worldwide, leading to chronic liver disease in at least 50% of infected individuals. The pathogenic mechanisms that result in chronic hepatitis are unknown. Lymphocytes are typically observed within the hepatic parenchyma, but the functional characteristics of these cells have not been defined.

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We have previously described a subline of L1210 murine leukemia cells (LL1) selected in a low level of 5-formyltetrahydrofolate which overexpresses a membrane-bound folate-binding protein (FBP1) and exhibits a rearrangement at the locus encoding this protein. Genomic clones containing the entire FBP1-encoding DNA from both L1210 and LL1 were isolated and characterized. Sequence analysis indicates that, with exception of the 5'-region, the FBP1-encoding locus in both cell lines is identical.

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Hepatitis C virus (HCV) antigen was detected immunohistochemically using fluorescein isothiocyanate-labeled immunoglobulin G fractions from chimpanzee and human sera strongly reactive with recombinant hepatitis C virus structural and non-structural proteins. The antigen was localized in the cytoplasm of hepatocytes in all 9 chimpanzees with acute hepatitis C, in 5 of 10 chimpanzees with chronic HCV infection, and in 11 of 12 patients with chronic hepatitis C. The specificity of the hepatocellular HCV and FITC-labeled probes for HCV was ascertained by blocking studies with paired serum samples obtained from 8 infected and uninfected chimpanzees or from 14 patients during the acute and chronic phases of HCV infection.

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A variety of methods exists for measuring individual particle dimensions as a means of characterizing particle size, size distribution, and shape. The equipment described in this report belongs to the class of semiautomatic non-TV-interfaced analyzers. Unlike many existing image analysis systems, three-dimensional form measurements and texture data for the calculation of particle size and shape parameters can be determined easily and directly from each particle profile using this system.

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Objectives: To determine the prevalence and management of hearing loss and hearing handicap among non-demented nursing home residents.

Design: Descriptive study of total population of two nursing homes.

Participants: All 121 eligible residents.

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Many cases of chronic hepatitis and cirrhosis cannot be attributed to a known cause and are collectively referred to as cryptogenic chronic liver disease. We have evaluated the role of the hepatitis C virus in the pathogenesis of this condition in a retrospective serum analysis for antibody to hepatitis C virus in 129 patients with cryptogenic liver disease. Other causes of chronic hepatitis and cirrhosis were ruled out by clinical, serum biochemical and serological techniques.

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A second generation ELISA for combined detection of antibodies to three hepatitis C virus (HCV) recombinant proteins, i.e. C100, C33c and core, was compared with a first generation anti-HCV ELISA in which only antibodies to C100 are detected.

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To establish the effect of interferon alpha-2B (IFN-alpha) treatment on hepatitis C virus (HCV) viremia, rather than monitor the alanine aminotransferase (ALAT) values we measured HCV-RNA by cDNA-polymerase chain reaction (cDNA-PCR) in plasma before and during IFN-alpha treatment. Eight hemophilia patients with chronic hepatitis C were treated with IFN-alpha for 24 weeks: 5 MU daily for 2 weeks, 2.5 MU daily for 4 weeks, and 1.

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Detection of early antibody to hepatitis C virus (HCV) by a new second-generation C200/C22 anti-HCV enzyme-linked immunosorbent assay (ELISA) and a four-antigen recombinant immunoblot assay (4-RIBA) was compared with the first-generation anti-HCV C100 ELISA using sequential serum samples of 9 recipients who were infected with HCV, as detected by polymerase chain reaction after transfusion of blood products. Within 26 weeks after transfusion, 9/9 (100%) recipients seroconverted with C200/22 ELISA, and 6/9 (67%) seroconverted with C100 ELISA. Compared with C100 ELISA, C200/C22 ELISA seroconversion occurred simultaneously in 3 cases, 5-6 weeks earlier in 3 other cases, and 20 weeks earlier in 1 case.

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The nucleic acid sequence of the putative 5'-untranslated (5PUT) region of hepatitis C virus (HCV), determined for samples obtained from a variety of geographic origins, was found to be over 98% conserved among all isolates. On the basis of this signature sequence for HCV, a viral RNA assay was developed by using cDNA synthesis with reverse transcriptase, followed by polymerase chain reaction (PCR). The new assay was compared with the Ortho-Chiron C100-3 HCV enzyme-linked immunosorbent assay to research radioimmunoassays for antibodies to the C33c and C22 HCV antigens and to the first reported set of HCV PCR primers designed from the NS3 domain.

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Hepatitis C virus antibodies were measured in 213 patients who had acute (n = 122) and chronic (n = 91) non-A, non-B hepatitis. In acute infection, anti-hepatitis C virus was detected in 61% of IV drug abusers, in 33% of patients with transfusion-associated hepatitis, and in 22% of patients with sporadic infections (P less than 0.0005, drug abusers vs.

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L1210 murine leukemic cells grown under conditions of continuous low folate concentrations acquire increased levels of a high affinity/low capacity folate-binding protein (FBP). Using an oligonucleotide probe complementary to the human FBP, we have cloned and sequenced two murine FBP cDNAs isolated from a library constructed using a L1210 subline adapted for growth on low levels of 5-formyltetrahydrofolate. The encoding proteins, designated FBP1 and FBP2, have predicted Mr values of 29,415 and 28,821, respectively.

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To assess the contribution of the recently identified hepatitis C virus to chronic liver diseases of unknown cause and chronic hepatitis attributed by exclusion to non-A, non-B hepatitis, we tested for antibody to hepatitis C in hepatitis B surface antigen-negative patients with a spectrum of chronic liver diseases. Antibody to hepatitis C virus, a marker of hepatitis C infection, was detected with a first-generation radioimmunoassay at the following frequencies in the following patient groups: 69% of transfusion-associated non-A, non-B hepatitis; 53% of non-transfusion-associated non-A, non-B hepatitis; 26% of hepatitis B surface antigen-negative hepatocellular carcinoma; 8% of cryptogenic cirrhosis; 5% to 7% of autoimmune chronic liver diseases; 19% of patients with miscellaneous types of chronic liver disease; and 0.67% of healthy controls.

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Hepatitis C virus (HCV) is the major etiologic agent of parenterally transmitted non-A, non-B hepatitis. To determine whether there is a relationship between this virus agent and hepatocellular carcinoma (HCC), the sera of patients with HCC and chronic hepatitis were assessed using a sensitive immunoassay for HCV antibody. Anti-HCV was detected in 65% of 132 patients with HCC, without any relationship with the presence of the hepatitis B surface antigen (HBsAg).

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There is evidence that hepatitis C virus (HCV) may be vertically transmitted from infected mothers to their children. To test this hypothesis, we prospectively studied 10 pregnant women at high risk from parenterally or sexually transmitted diseases with the polymerase chain reaction. HCV RNA was found in 8 newborn babies delivered by women who were anti-HCV seropositive, and persisted for 2-19 months of follow-up.

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Although hepatocellular carcinoma is a relatively uncommon tumor in the United States, it is quite common in sub-Saharan Africa and the Far East, where most cases are associated with infection with the hepatitis B virus. We have studied 99 American patients with hepatocellular carcinoma for evidence of hepatitis B or hepatitis C viral infection and compared these findings to those in a group of matched controls with other cancers. The two groups differed in proportion, with hepatitis B surface antigen in serum being significantly higher in patients with hepatocellular carcinoma (7% vs.

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We have determined the nucleotide sequence at the extreme 5' and 3' termini of the hepatitis C virus (HCV) genome. Our analyses of these sequences show (i) the nucleotide sequence in the 5' untranslated region is highly conserved among HCV isolates of widely varying geographical origin, (ii) within this region, there are blocks of nucleotide sequence homology with pestiviruses but not with other viruses, (iii) the relative position of short open reading frames present in the same region of the HCV genome is similar to that of the pestiviral genome, (iv) RNAs truncated at the 5' and 3' ends are found, but the origin and functions of these RNAs are unknown, and (v) poly(A) tails appear to be present on 3' subgenomic RNAs. These data differentiate HCV from the flaviviruses and indicate a closer evolutionary relationship of HCV with the pestiviruses.

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Based on the flavi- and pestivirus model of genome organization for the hepatitis C virus (HCV) (1-5), the nucleotide and deduced amino acid sequences of the putative envelope (E1) and the junction between the E1 and NS1/envelope 2 (E2) region from six different human isolates of HCV were compared with the nucleotide and predicted amino acid sequences of the prototype hepatitis C virus (HCV-1) (5). The overall percentage of nucleotide and amino acid changes among all six isolates, including HCV-1, from nucleotide 713 to 1630 (amino acid 129 to 437) was between 3 and 7%, which is comparable to that seen in some flaviviruses (6-8). An analysis of the number of nucleotide and deduced amino acid sequence changes among all six isolates and HCV-1 revealed a moderately variable domain of approximately 40 amino acids in the E1 region and a hypervariable domain (Region V) of approximately 28 amino acids, which is directly downstream from a putative signal peptide sequence, in the junction between E1 and NS1/E2.

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