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Biomedical subjects

W L Irving

Publications and source records attributed to W L Irving.

At least 37 records · Page 2Linked to original sources
PubMed1998

Hepatitis G infection: role in cryptogenic chronic liver disease and primary liver cell cancer in the UK. Trent Hepatitis C virus Study Group.

Hepatitis G virus (HGV) is a flavivirus that can cause acute hepatitis and persistent infection but its role in chronic liver disease or primary liver cancer is unproven. In this study we have examined the prevalence of HGV RNA in the serum of patients with hepatitis C virus (HCV) infection and in patients with cryptogenic chronic liver disease, including non-alcoholic steatohepatitis (NASH), and in patients with HCV-related hepatocellular carcinoma (HCC) and HCC arising in patients with cryptogenic liver disease. One-hundred and thirty patients who were positive for antibody to HCV (anti-HCV), 54 patients with cryptogenic chronic liver disease (including 17 patients with NASH) and 46 patients with hepatitis C-related (n = 27) or cryptogenic liver disease-related HCC (n = 19) were studied. HGV RNA was detected using nested reverse transcriptase-polymerase chain reaction (RT-PCR) and was found in 16.1% of patients with HCV infection. HGV RNA was not detected in any patient with cryptogenic liver disease. In patients with HCC, 7/34 samples were positive for HGV RNA and six out of seven HGV-positive subjects also had HCV infection. Only one patient with HCC in cryptogenic liver disease was positive for HGV RNA. Hence, cryptogenic liver disease in the UK is not caused by HGV/GBVc infection. It seems unlikely that HGV plays a significant role in hepatocarcinogenesis.

Carcinoma, Hepatocellular↗
PubMed1998

Association between MHC class II alleles and clearance of circulating hepatitis C virus. Members of the Trent Hepatitis C Virus Study Group.

The frequencies of HLA class I antigens and class II haplotypes were compared in subjects with previous (polymerase chain reaction [PCR]-negative) or with persistent (PCR-positive) hepatitis C virus (HCV) infection and in HCV patients with mild versus severe histologic activity scores on liver biopsy. The DRB1*11 allele group was found in 11 (31.4%) of 35 subjects with previous infection and in 11 (8.2%) of 135 subjects with persistent infection (P < .001). The DQB1*0301 allele was found in 18 (51.4%) of 35 subjects with previous infection and in 33 (24.4%) of 135 patients with persistent infection (P < .002). Both observations remained significant after correction for multiple testing. No significant association was shown between severity of disease and any HLA class I or II type. Thus, the HLA class II alleles DRB1*11 and DQB1*0301 are associated with clearance of circulating HCV.

Adult↗
PubMed1998

Effect of genotypes on the quantification of hepatitis C virus (HCV) RNA in clinical samples using the Amplicor HCV Monitor Test and the Quantiplex HCV RNA 2.0 assay (bDNA).

The Amplicor HCV Monitor test and the Quantiplex HCV RNA 2.0 (bDNA) assay are two commercially available assays for the quantification of hepatitis C virus (HCV) RNA in clinical samples. A direct comparison of the two assays was carried out using sera frozen previously from patients known to be chronically infected with HCV. Overall, 61 samples from 51 patients were tested simultaneously by the two methods: 67% (28/42) of the patients were infected by HCV genotype/serotype 1, 10% (4/42) with type 2, and 24% (10/42) with type 3. When the absolute value from each assay was examined, the Quantiplex assay gave a consistently higher reading and the mean logarithmic difference between the two assays was 1.4 (1.0 in type 1, 2.0 in type 2, and 2.2 in type 3). When analyzed according to genotype, strong correlation was observed between the two assays for type 1 (r = 0.83, 95% CI 0.63-0.93, P < 0.01), but not for nontype 1 samples. Despite the difference in absolute level reported by the two assays, there was a consistent trend of change in HCV RNA concentration by both assays in patients whose consecutive samples were analyzed and the differences between the two assays in consecutive samples were within 0.4 log of each other. The results suggested that with samples containing genotype 1, the Amplicor assay was more sensitive than the Quantiplex assay by about one log. However, the sensitivities of the two assays with nontype 1 samples were much closer probably due to the failure of the Amplicor assay to quantify nontype 1 genotypes effectively.

Adolescent↗
PubMed1996

Serum HCV RNA levels assessed by quantitative NASBA: stability of viral load over time, and lack of correlation with liver disease. The Trent HCV Study Group.

BACKGROUND/AIMS: We used the hepatitis C virus quantitative NASBA technique to evaluate the stability of viral load within individuals with chronic hepatitis C, to determine the range of viraemic load between individuals, and to assess the usefulness of hepatitis C virus RNA quantitation in predicting the severity of underlying hepatitis C virus-induced liver disease. METHODS: Hepatitis C virus RNA was determined, using the quantitative NASBA assay, in multiple serum samples from 11 individuals with chronic hepatitis C over an average time period of 11 months (range = 3-23 months), and in single serum samples from a further 10 individuals. RESULTS: In 10/11 individuals the hepatitis C virus RNA titres were within one log10 copies/ml of each other during this time period. In the eleventh, there was a rise of 1.36 log10 copies/ml in two serum samples taken 8 months apart. The viraemic load varied by 2.79 log10 copies/ml serum between individuals. There were no correlations between mean RNA levels and total biopsy scores (either Knodell or Sheffield scores), or the individual components of the biopsy scoring systems, except the sinusoidal infiltration component of the Sheffield score. There was also no difference in viral RNA levels between those infected with type 1 as compared to type 3 virus, with a mean level in both groups of 7.2 log10 copies/ml. CONCLUSIONS: Hepatitis C virus serum RNA level is stable within individuals within the studied time period. Viral load varies between infected individuals but is not a useful prognostic indicator of the severity of virus-induced liver disease.

Adult↗
PubMed1996

The presence of rheumatoid factor in sera from anti-HCV positive blood donors interferes with the detection of HCV-specific IgM. Trent HCV Study Group.

BACKGROUND/AIMS: IgM anti-HCV has been reported as a useful marker of disease activity and of likely response to interferon therapy in patients with chronic hepatitis C virus infection. Sera from patients with hepatitis C virus infection may contain rheumatoid factor. This study was designed to investigate the possible effect of rheumatoid factor in an IgM anti-HCV assay. METHODS: Sera from 75 blood donors with chronic hepatitis C virus infection were tested for the presence of IgM anti-HCV using a core-derived peptide as antigen, before and after removal of IgG. These sera and appropriate control sera were also tested for the presence of rheumatoid factor. RESULTS: Removal of IgG prior to IgM testing resulted in a significant loss of reactivity in the IgM anti-HCV assay in 30/41 sera that were positive in this assay when tested untreated. Seventy per cent of anti-HCV positive sera were also positive for rheumatoid factor. CONCLUSIONS: Rheumatoid factor causes significant false positive reactivity in IgM anti-HCV detection assays. The results of assays that do not account for this interference should be viewed with caution.

Antibody Specificity↗
PubMed1996

Studies to show that with podophyllotoxin the early replicative stages of herpes simplex virus type 1 depend upon functional cytoplasmic microtubules.

The antiviral activity of podophyllotoxin against herpes simplex type 1 virus (HSV-1) grown in Vero cells was studied by a simple microtitration assay. Antiviral effects were induced at similar concentrations as direct cellular toxicity, as characterised by a time-dependent loss of cell monolayer. Podophyllotoxin-mediated toxicity arises from cytoplasmic microtubular, and hence cytoskeletal, decay. Some degree of selectivity was seen for inhibition of virus replication over direct cellular toxicity. Podophyllotoxin acted against an early viral process, as an antiviral effect was still seen if drug was removed 2 h after infection. Similar effects were seen with colchicine, a classical tubulin-binding compound, but not with bromovinyldeoxyuridine. Podophyllotoxin was capable of inducing a cytoprotective effect in Vero cells, as pre-treatment of cells abrogated virus growth for up to 90 min after removal of drug. This is coincident with the repolymerisation of cellular microtubules and re-formation of the cytoskeleton. We conclude that HSV-1 relies upon a functional cellular cytoskeleton for efficient completion of an early replicative event. Such a process may be the transport of viral material to the nucleus or inhibition of the formation of intranuclear viral 'replication factories', bodies containing cytoskeletal fragments constructed after viral infection.

Animals↗
PubMed1995

Enhanced expression of MHC class I molecules on cultured human thyroid follicular cells infected with reovirus through induction of type 1 interferons.

Certain viruses are known to modulate the cellular expression of MHC molecules. We have investigated whether reovirus types 1 or 3 can alter the normal MHC molecule expression on cultured human thyroid follicular cells (TFC). Primary TFC cultures were established from eight human thyroid donors and MHC class I and II expression was assessed by indirect immunofluorescence microscopy. Both types of reovirus enhanced MHC class I expression on TFC from all thyroid donors. Class II MHC protein was strongly induced by type 1 reovirus on TFC from one donor, while weak induction of expression, by either reo-1 or reo-3 virus, was noted on the TFC of five other donors. Studies on the mechanism(s) of MHC class I hyperexpression showed that mouse MoAb against the type 3 reovirus haemagglutinin (anti-HA3) reduced the ability of the virus to induce hyperexpression of class I MHC molecules on TFC. However, supernatant harvested from type 3 reovirus-infected TFC cultures maintained its ability to enhance class I expression after incubation with anti-HA3. Moreover, adding rabbit anti-sera to interferon-alpha (IFN-alpha) or IFN-beta inhibited the increased class I MHC expression on TFC by both types of reovirus. These data suggest that reoviruses (types 1 and 3) can enhance MHC class I on cultured TFC. The mechanism of MHC class I enhancement is most probably through the release of IFN-alpha and IFN-beta.

Antibodies, Monoclonal↗
PubMed1993

Interaction of hepatitis B and hepatitis C infection in haemophilia.

The management of haemophilia has been greatly complicated by the clinical sequelae of viral infection acquired through contaminated blood products. Many haemophiliacs have been infected by several viruses and the interaction between these viruses may be complex. In a cohort of 42 anti-HCV positive haemophiliacs, five were also found to be positive for HBsAg. All five were HCV reverse transcriptase/PCR negative compared to the 4/37 (11%) anti-HCV positive haemophiliacs who were HBsAg negative (P = 0.0001). We have identified a striking interaction between hepatitis C (HCV) and hepatitis B (HBV) in haemophiliacs co-infected by these agents, suggestive of the phenomenon of viral interference.

Cohort Studies↗