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Biomedical subjects

W L Irving

Publications and source records attributed to W L Irving.

At least 55 records · Page 3Linked to original sources

Use of anti-GOR testing in the screening of blood donors for hepatitis C virus infection.

Sera from 12/1,155 (1%) anti-HCV-negative (Elisa) UK blood donors were found to be anti-GOR positive. None out of 12 of those sera were positive for HCV RNA by the reverse transcriptase/polymerase chain reaction (RT/PCR). In a cohort of 316 anti-HCV Elisa-positive sera, 27/57 RIBA-positive, and 1/188 RIBA-negative sera were anti-GOR positive, resulting in a sensitivity of 47% and a specificity of 99.5% for anti-GOR as a marker for RIBA-confirmed HCV infection. Four out of 71 (6%) of RIBA-indeterminate sera were anti-GOR positive. Donors with anti-GOR reactivity were more likely to have antibodies against each of the individual HCV antigens represented in the RIBA, and those antibodies were of greater intensity, when compared to the anti-GOR negative cohort. Twenty out of 36 (55.6%) of RT/PCR-positive sera were anti-GOR positive, compared to 1/7 (14.3%) of RT/PCR-negative sera (p = 0.09). The usefulness of anti-GOR testing of UK blood donors is discussed in the light of these results.

Autoantibodies↗

Detection of immunoglobulin M antibodies to glycoprotein G-2 by western blot (immunoblot) for diagnosis of initial herpes simplex virus type 2 genital infections.

Western blots (immunoblots) for the detection of immunoglobulin M (IgM) antibodies specific for herpes simplex virus type 1 (HSV-1) and HSV-2 in patients' sera were developed. The locations of the type-specific glycoprotein G (gpG-2) of HSV-2 (92- and 140-kDa forms) and glycoprotein C of HSV-1 (gpC-1), which carries mostly type-specific antigenic epitopes, were checked with specific monoclonal antibodies. Western blot assays for IgM antibody to gpC-1 or gpG-2 were performed after depletion of IgG by precipitation with anti-human IgG. In patients with primary HSV-2 genital infections, seroconversion of IgM and IgG antibodies to both the 92- and 140-kDa forms of gpG-2 was observed, although both antibodies appeared in convalescent-phase serum after the first week. IgM and IgG antibodies to low-molecular-size polypeptides (40 to 65 kDa) were the first antibodies observed in patients with primary infection, but these antibodies were cross-reactive with HSV-1 and HSV-2. However, in patients with recurrent HSV-2 infections, IgG antibodies to both forms of gpG-2 and the low-molecular-size polypeptides were found no matter how early after onset the patient was bled, and IgM to gpG-2 did not appear. In patients with nonprimary initial genital HSV-2 infections, IgG antibody to HSV-1 was demonstrated in the first serum specimen, and HSV-2-specific IgM was found in 39% of the serum specimens. Hence, the Western blot assay can be used to test for IgM antibody to gpG-2, allowing for the retrospective diagnosis of inital HSV-2 infections and its use as a supplementary test to the gpG-2 IgG enzyme-linked immunosorbent assays developed elsewhere. In contrast, IgM antibody to gpG-2 is not usually detected in patients with recurrent HSV-2 infections.

Adult↗

Idiopathic pulmonary fibrosis and hepatitis C virus infection.

A possible role for hepatitis C virus (HCV) infection in the pathogenesis of idiopathic pulmonary fibrosis (IPF) has recently been suggested on the basis of an unusually high seroprevalence rate of anti-HCV in such patients from Japan. In an attempt to confirm these findings, we tested sera from 62 patients with IPF by two second-generation anti-HCV ELISAs. Only one serum was reactive. Serum from this patient gave an indeterminate result when tested by four-antigen RIBA (c22 band only), and it was negative for the presence of HCV RNA when tested by the reverse transcriptase polymerase chain reaction assay. HCV infection is thus no more prevalent in patients with IPF from the UK than in the general population.

Aged↗

The reliability of serological tests for the diagnosis of genital herpes: a critique.

The reliability and limitations of the currently used routine tests for herpes simplex virus type 2 (HSV-2) antibody in Australia are reviewed. Six case reports illustrate the clinical dangers of overinterpretation of the currently available kits and the need for a readily available specific HSV-2 antibody test. In Sydney, HSV-2 causes approximately 85% of primary genital herpes and > 95% of recurrent genital herpes. Due to the extensive serological cross-reactivity between HSV-1 and HSV-2, currently available "type specific" commercial assays cannot reliably distinguish between the 2. Isolation of herpes simplex virus (HSV) or detection of HSV antigen in vesicle fluid is the preferred diagnostic test but may be overlooked or patients may have no visible lesions. The only accurate techniques for detecting HSV-2 specific antibody are the Western blot assay and an enzymatic immunoassay using glycoprotein G (gG-2), a component of the HSV-2 envelope. These tests, which still are restricted to research laboratories can be used to accurately identify people with previous exposure to HSV-2 (IgG) or to diagnose primary infection where virus isolation has not been performed or is impossible. Current commercially available antibody tests may have extensive cross-reactivity.

Adolescent↗

Serological diagnosis of infection with human herpesvirus type 6.

OBJECTIVE: To identify clinical consequences of acute human herpesvirus type 6 infection by hypothesising that the virus will induce similar clinical syndromes to cytomegalovirus. DESIGN: Examination of consecutive serum samples from patients with illnesses compatible with acute cytomegalovirus infection or exanthem subitum by indirect immunofluorescence for the presence of antibodies to human herpesvirus type 6. An IgG absorption step was included to avoid false positive and negative results for IgM. The criterion standard for diagnosis of human herpesvirus type 6 infection was the presence of IgM human herpesvirus type 6 antibody (titre greater than 20) and a rising titre of IgG human herpesvirus type 6 antibody without serological evidence of alternative infection. SETTING: Routine viral diagnostic and reference laboratory in the largest teaching hospital in Sydney. PATIENTS: 341 Consecutive serum samples were analysed from patients with hepatitis (147 samples); infectious mononucleosis-like illness (106); screens for toxoplasma, other viruses, rubella, cytomegalovirus, and herpesvirus (38); fever in an immunocompromised patient (eight); unusual neurological (nine) or haematological syndromes (14); splenomegaly (six); and rash in a child (13). RESULTS: Three cases of acute human herpesvirus type 6 infection were identified: in one patient aged 65 with a previous diagnosis of acute non-A non-B hepatitis, one aged 25 with a glandular fever-like illness, and one aged 6 with a glandular fever-like illness. All three illnesses resolved completely. 15 Further serum samples were positive for human herpesvirus type 6 antibody but were also diagnostic for acute infection with other viruses (cytomegalovirus (nine), Epstein-Barr virus (three), and HIV (one] or had a titre of IgM human herpesvirus type 6 antibody less than 20 (two). CONCLUSIONS: Acute human herpesvirus type 6 infection in immunocompetent patients may result in a mononucleosis-like illness or an acute but self limiting hepatitis.

Adult↗

Dual antibody rises to cytomegalovirus and human herpesvirus type 6: frequency of occurrence in CMV infections and evidence for genuine reactivity to both viruses.

The frequency of high (greater than 256) IgG anti-human herpesvirus type 6 (HHV-6) titers in sera known to be positive for IgM anti-cytomegalovirus (CMV) or IgM anti-Epstein Barr virus (EBV) was significantly greater than in sera from healthy controls or from a group of ill patients who were CMV and EBV IgM-negative (15/25 and 17/25 vs. 1/25 and 2/25, respectively, P less than .001). There was serologic evidence of simultaneous HHV-6 infection or reactivation (a rise in IgG anti-HHV-6 titer or the presence of IgM anti-HHV-6) in sera from 14 of 17 primary CMV infections. In 5 of the 10 patients with concurrent rises in IgG titers to both viruses, the rise in IgG anti-HHV-6 preceded that of IgG anti-CMV. Complete removal of IgG anti-CMV reactivity from 5 sera from patients who had a primary CMV infection with a rise in IgG anti-HHV-6 titer had no effect on the IgG anti-HHV-6 titer of those sera, demonstrating that the rise in HHV-6 IgG titer was not a consequence of anti-CMV antibodies cross-reacting in the HHV-6 IgG assay.

Adult↗

Roseola infantum and other syndromes associated with acute HHV6 infection.

Eight cases of acute human herpesvirus type 6 (HHV6) infection in infants were diagnosed serologically by the demonstration of IgM anti-HHV6 (8/8) and a significant change in total anti-HHV6 antibody titre (6/8). Four infants were sufficiently ill to require admission to hospital and further investigations: one with encephalitis and three with gross hepatosplenomegaly, two of whom had evidence of simultaneous infection with another herpes-virus. The remaining four infants had an illness compatible with roseola infantum, although this diagnosis had not been made clinically. Sera from two of those infants with rash had been sent for analysis to exclude rubella because the infants' mothers were pregnant. The other two had received antibiotics when febrile, and the subsequent appearance of the roseola rash had raised the possibility of antibiotic allergy. The data suggest that there are clinical syndromes in addition to roseola infantum associated with the presence of IgM anti-HHV6, in which serological screening for evidence of acute HHV6 infection may be useful.

Antibodies, Viral↗

In situ hybridization studies of adenoviral infections of the lung and their relationship to follicular bronchiectasis.

We have used a probe against the adenovirus genome to study cultured epithelial cells specifically infected with various types of adenovirus and Graham 293 cells, which contain few copy numbers of a fraction of the adenovirus genome. We have also examined lung tissue obtained from three cases of acute adenovirus pneumonia, two cases of adenovirus pneumonia that had passed through the acute phase, and nine cases of follicular bronchiectasis. Our purpose was to determine whether the probe was effective in detecting a wide variety of adenovirus types, to determine whether it could detect adenovirus in lung tissue that had been fixed and stored in paraffin blocks for several years, and to test the hypothesis that adenovirus was an important cause of follicular bronchiectasis. The results show that the probe was able to detect adenovirus from Genera B1, B2, C, D, and E with a sensitivity of 5 to 10 copies/cell. The probe also detected adenovirus in 14 of 14 slides from three cases of acute disease, but failed to obtain a positive result in the cases examined after an acute infection or in any of the cases of follicular bronchiectasis. We conclude that the in situ hybridization technique is useful in the investigation of active adenovirus infection of the lung. The failure to show that the virus persisted in the chronic respiratory disease that follows adenovirus infection, or that it was present in cases of follicular bronchiectasis could be due to either a true absence, or to its presence in a latent form that is below the level of sensitivity of this technique.

Adenoviridae Infections↗

The effects of cyclosporin A on the early responses of B and T cells to Epstein-Barr virus infection.

The immunosuppressive properties of the fungal metabolite Cyclosporin A (CsA) on the human lymphocyte response to the polyclonal B cell activator Epstein-Barr virus (EBV) in vitro were assessed. CsA showed both stimulatory and inhibitory effects on EBV-induced IgM secretion, the net effect being dependent on the dose of virus used. T cells were required for both these effects to occur. A model is proposed to account for the complex interactions of CsA in this system.

Antibody Formation↗