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Biomedical subjects

C G Teo

Publications and source records attributed to C G Teo.

At least 55 records · Page 3Linked to original sources

Low detection rate and maternal provenance of hepatitis B virus S gene mutants in cases of failed postnatal immunoprophylaxis in England and Wales.

Hepatitis B virus (HBV) infection occurred despite full passive-active immunoprophylaxis in 20 of 321 infants born to mothers seropositive for hepatitis B e antigen. In 2 (12%) of 17 infected infants, mother-infant DNA sequence mismatches were found in a segment of the HBV S gene coding for antigenic determinants of the HBV surface antigen (HBsAg) amplified from sera by polymerase chain reaction (PCR). Point substitutions occurred in codons 120, 134, and 144 of the HBsAg polypeptide in the variant sequence of 1 infant and in codon 126 in the other; all were missense mutations. Mutant sequences could not be recovered from maternal sera by PCR cloning but were selectively generated using an amplification refractory mutation system. The frequency of potential vaccine escape mutants is therefore low, and these preexist maternally as minor variants.

Amino Acid Sequence↗

Oral hairy leukoplakia: clinicopathologic features, pathogenesis, diagnosis, and clinical significance.

Oral hairy leukoplakia (OHL) is a lesion frequently, although not exclusively, observed in patients infected by human immunodeficiency viruses (HIV). OHL is clinically characterized by bilateral, often elevated, white patches of the lateral borders and dorsum of the tongue. Histologically, there is profound acanthosis, sometimes with koilocytic changes, and a lack of a notable inflammatory infiltrate. The koilocytic changes are due to intense replication of Epstein-Barr virus (EBV), while epithelial hyperplasia and acanthosis are likely to result from the combined action of the EBV-encoded proteins, latent membrane protein-1, and antiapoptotic BHRF1. How OHL is initiated and whether it develops after EBV reactivation from latency or superinfection remain unresolved; nevertheless, definitive diagnosis requires the demonstration of EBV replicating vegetatively in histological or cytological specimens. In patients with HIV infection, the development of OHL may herald severe HIV disease and the rapid onset of AIDS, but despite its title, OHL is not regarded as premalignant and is unlikely to give rise to oral squamous cell carcinoma.

HIV↗

Presence of human herpesvirus 8 variants in the oral tissues of human immunodeficiency virus-infected persons.

A 210-bp DNA segment specific to the human herpesvirus 8 (HHV-8) genome was amplified by nested polymerase chain reaction from 10 of 14 archived oral biopsy samples of HIV-positive patients in London who had no evidence of oral Kaposi's sarcoma (KS). Various oral sites were represented. Oral tissues from 20 general dental patients not known to be HIV-infected were negative. When DNA sequences of these products were compared with sequences derived from 5 oral KS tissues of AIDS patients in London and 10 skin biopsies of Italian patients with Mediterranean KS (total number of positive tissues = 25), 11 were found to be unique. DNA and predicted peptide motifs of these sequences were also different from those in 28 of 36 HHV-8-positive lesions previously reported from American and African patients. HHV-8 is tropic for the oral mucosa of HIV-infected persons, and HHV-8 variants, though diverse, may be geographically restricted.

Amino Acid Sequence↗

HCV genotypes in Italian patients with HCV-related oral lichen planus.

Hepatitis C virus (HCV) has high genomic variability and since its discovery, six different "types" and an increasing number of "subtypes" have been reported. HCV genotype may influence viral replication, natural history of disease and response to therapy. Recently, an association between lichen planus (LP) and HCV infection has been suggested, as there is an increased frequency of HCV infection among some groups of patients with LP, in particular from Italy and Japan. These results have not been confirmed by other reports from different geographical areas. Since HCV genotypes have a heterogeneous geographical distribution, we have determined by restriction fragment length polymorphism the genotypes of 39 HCV-seropositive Italian patients with oral LP in order to establish whether the association between LP and HCV infection is influenced by HCV subtype. Of the 33 (84.6%) viraemic patients, 17 (51%) were infected by HCV subtype 1b, 9 (27%) were infected by HCV subtype 2a, 2 by subtype 1a and 1 by subtype 2b. In four cases the gel patterns were uninterpretable. This distribution of HCV genotypes is similar to that reported in recent studies of Italian HCV-seropositive patients of unknown LP status. It is concluded from this small sample that the association of lichen planus with HCV infection and its differential geographic distribution is unlikely to be due to infection by a particular HCV genotype.

Adult↗

Detection of human herpesvirus-8 DNA in oral ulcer tissues of HIV-infected individuals.

OBJECTIVE: To determine the frequency of detection of human herpesvirus-8 (HHV-8) in HIV-related oral ulcers. DESIGN: Analysis of archived biopsy material. METHODS: Nested polymerase chain reaction of DNA extracts. RESULTS: HHV-8 DNA was detected in six of 10 oral ulcers of HIV-positive patients without oral Kaposi's sarcoma (KS) lesions and five of 11 oral KS lesions. The positive non-KS samples were derived from various oral sites. CONCLUSIONS: In HIV-positive people, HHV-8 can infect oral tissues that are not affected by KS.

AIDS-Related Opportunistic Infections↗

Risk factors associated with Epstein-Barr virus replication in oral epithelial cells of HIV-infected individuals.

OBJECTIVE: To examine risk factors associated with Epstein-Barr virus (EBV) replication in the oral epithelium of an HIV-infected cohort. DESIGN: Longitudinal study of behavioural, medication and immunological parameters of HIV-1-seropositive outpatients attending a genitourinary clinic. Outcome measure was EBV DNA positivity in curetted oral squames, as detected by in situ hybridization. Logistic regression for repeated observations of the same individuals was used to analyse how risk changed over time. RESULTS: Fifty six individuals were studied; 158 patient-visits were made in total (mean, 2.8). Of 137 samples curetted from the tongue, 36 were positive for EBV DNA. Recreational drug use, oral sexual practices, therapy with zidovudine and aciclovir, and changes in CD4 and total lymphocyte counts were not associated with changes in risk. Alcohol drinking, elevated CD8 lymphocyte counts and fluconazole therapy were associated with a decreased risk, and cigarette smoking with increased risk. CONCLUSION: Behavioural and HIV-specific immunological changes may play important roles in promoting and affecting the course of oral EBV replication. Rigorous anticandidal therapy and avoidance of cigarette smoking may retard the development of oral hairy leukoplakia.

AIDS-Related Opportunistic Infections↗

Measurement of antibody avidity for hepatitis C virus distinguishes primary antibody responses from passively acquired antibody.

A new IgG antibody avidity test for hepatitis C virus (HCV) has been developed and was validated using sera from 12 renal dialysis patients infected with HCV. In primary HCV infection low avidity antibody (mean avidity index 24%) was detected within 50 days of seroconversion whereas in long-term infection (at least 300 days after seroconversion), the mean avidity index was high (88%); in five patients, the avidity index was shown to increase rapidly as time elapsed after primary infection, whereas immunosuppressive therapy was found to delay maturation of the immune response in two further patients. The assay was then employed to confirm that a spurious outbreak of primary HCV infection in eight bone marrow transplant patients was explicable by passive acquisition of high avidity anti-HCV after intravenous immunoglobulin therapy. It is concluded that this avidity test will have an important role in the investigation of HCV infection in patients.

Antibody Affinity↗

Transmission of hepatitis B virus analyzed by conformation-dependent polymorphisms of single-stranded viral DNA.

Hepatitis B virus (HBV) DNA from regions coding for surface and core antigens were amplified and radiolabeled from hepatitis B surface antigen (HBsAg)-positive serum samples by polymerase chain reaction, heat-denatured, and analyzed for conformation-dependent polymorphisms by gel electrophoresis under nondenaturation conditions. Analysis of serum samples representative of diverse and identical HBsAg subtypes showed a wide range of autoradiographic banding patterns, each unique to the specimen. Serial samples of a long-term carrier showed relative stability of banding patterns over time. Epidemiologic analyses using this procedure showed banding patterns of case subjects to be identical to those of persons implicated as the source. This facile and discriminatory approach to the differentiation of viral strains should be useful in the study of HBV transmission.

Adult↗

Peptide based enzyme immunoassays for detecting hepatitis C antibodies in sera of people at high risk.

AIM: To evaluate the performance of three newly introduced enzyme immunoassays (EIAs) for hepatitis C virus (HCV) antibodies, based on synthetic oligopeptides as antigens. METHODS: Referred serum samples (n = 173) from people representing groups at high risk of HCV infection were studied. An EIA based on second generation recombinant polypeptide antigens was used for comparison. EIA reactivities were validated by testing repeatedly reactive samples in two recombinant antigen based immunoblot assays. RESULTS: In samples from patients with liver dysfunction and those with bleeding disorders sensitivity of the three peptide based EIAs, manufactured by Innogenetics NV, Biokit SA, and United Biomedical Inc., were all 93%; specificity and efficiency were all greater than 95%. In samples from blood donors (previously tested as positive by the Ortho and Abbott Second Generation EIA) specificity, sensitivity, and efficiency were 95% or greater in all three peptide assays. Sensitivity, specificity, and efficiency of the recombinant antigen based Ortho Second Generation EIA were 100%, 89%, and 93%, respectively, in sera of patients with liver disease and those with bleeding disorders; and 100%, 43%, and 83%, respectively, in prescreened samples from blood donors. CONCLUSION: The peptide EIAs are more specific but less sensitive than the Ortho EIA. Peptide based EIAs should be useful in validating the specificity of Ortho EIA reactivities.

Hepacivirus↗

The virology and serology of hepatitis: an overview.

At least five viruses are recognised as causes of acute hepatitis which, in some instances, can develop into chronic disease. The viruses of hepatitis A (HAV) and hepatitis E (HEV) are spread predominantly by the faecal-oral route, whereas hepatitis B, C and D viruses (HBV, HCV and HDV) are spread by blood and other body fluids. The incubation period ranges from about four weeks for HAV to three months for HBV. The diagnosis mainly depends on the detection of various serological markers. The control of infection in the United Kingdom has been facilitated by the introduction of vaccines for HAV and HBV and screening blood for HBV and HCV. Good hygiene and sanitation, the availability of sterile equipment, and measures to modify the behaviour of high-risk groups such as injecting drug users, are also important in the prevention and control of viral hepatitis.

Biomarkers↗

Confirmation of second generation anti-hepatitis C virus enzyme immunoassays by antigenic cross-validation.

AIM: To determine if a scheme for validating enzyme immunoassay (EIA) results could be devised that did not require costly and methodically elaborate supplemental assays. METHODS: Samples (n = 525) from patients with haemophilia A, leukaemia, and chronic liver disease and at increased risk of hepatitis C virus infection were tested by EIA-1 (Ortho Diagnostics), an assay which uses recombinant HCV fusion proteins as antigens, and by EIA-2 (United Biomedical), an assay based on synthetic HCV oligopeptide antigens. RESULTS: Samples (n = 193) were repeatedly reactive in both EIAs. Of these, 190 (98%) yielded reactivities in both of two supplemental assays used, one an immunoblot assay (RIBA) using recombinant HCV polypeptides similar to EIA-1 antigens, and the other a neutralisation EIA (EIA-2N) based on antigenic competition with HCV peptides similar to EIA-2 antigens. The three samples not reactive in supplemental tests exhibited low EIA optical density (OD) values (signal/cutoff ratios of less than 3). Hence, all specimens reactive and yielding high OD values in both EIAs were also reactive in supplemental assays. Twenty four samples were reactive in EIA-1 only and nine (38%) of these were reactive in RIBA. Fourteen of the 15 (93%) specimens reactive in EIA-1 but not RIBA were derived from patients with chronic liver dysfunction. Two samples were reactive in EIA-2 only, of which one was reactive in EIA-2N and none in RIBA. CONCLUSIONS: Compared with EIA-2, EIA-1 yielded more validated reactive samples and resulted in more non-validated reactivities. It is therefore suggested that for clinical diagnosis: (i) EIA-1 be used for anti-HCV testing and EIA-2 for validation of EIA-1 reactivities; (ii) samples concordantly reactive in EIA-1 and EIA-2 and displaying high OD readings be considered HCV antibody positive without supplemental testing; (iii) supplemental testing by RIBA be limited to samples reactive in EIA-1 but equivocal or unreactive in EIA-2 and those concordantly reactive but exhibiting low absorbance readings.

Hemophilia A↗

Epstein-Barr virus receptors but not viral DNA are present in normal and malignant oral epithelium.

The presence and distribution of Epstein-Barr Virus receptors (EBVR's) on a range of normal (n = 18), dysplastic (n = 10) and malignant (n = 20) oral mucosa were studied by immunocytochemical methods using the monoclonal antibodies (MAb's) HB5 and B2. EBVR's were demonstrated as membrane staining of the spinous layers of normal non- and parakeratinized epithelium, indicating that EBVR's are differentiation-linked. This distribution was retained in dysplastic epithelium. Tissue from oral squamous cell carcinomas (SCC's) showed variable reactivity of only a few cells scattered randomly within the samples. Furthermore, a sensitive in situ hybridization (ISH) technique was used to determine if Epstein-Barr virus (EBV) was present in normal (n = 15) and oral squamous cell carcinoma tissue (n = 20). No EBV DNA was demonstrated within either normal or malignant epithelium, suggesting that the virus does not persist in normal oral stratified squamous epithelium nor is there any evidence for a role in oral carcinogenesis.

Adult↗