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Biomedical subjects

C G Teo

Publications and source records attributed to C G Teo.

At least 37 records · Page 2Linked to original sources

Effect of human immunodeficiency virus-1 protease inhibitors on the clearance of human herpesvirus 8 from blood of human immunodeficiency virus-1-infected patients.

The effect of human immunodeficiency virus-1 protease inhibitors on the frequency of human herpesvirus 8 DNA detection from peripheral blood of human immunodeficiency virus-positive persons was evaluated. Thirty-three human immunodeficiency virus-seropositive male patients were studied longitudinally. DNA from open reading frame 26 of the human herpesvirus 8 genome was amplified by the polymerase chain reaction from the CD45+ fraction of peripheral blood before and after the introduction of protease inhibitor therapy. Human herpesvirus 8 IgG status, CD4+ cell counts, and human immunodeficiency virus-1 plasma viral load were also assessed before and after therapy. When both reverse transcriptase inhibitor and protease inhibitor treatment were introduced at the same time, there was an increase in CD4+ T cell counts (P=0.0041), a decrease in human immunodeficiency virus plasma load (P=0.0584), and a decrease in the detection rate of human herpesvirus 8 DNA (P=0.0077). Introducing protease inhibitor to patients already receiving reverse transcriptase inhibitor treatment was associated with an increase in CD4+ T cell counts (P=0.0003), a decrease in human immunodeficiency virus plasma viral load (P=0.0911), and a decrease in the human herpesvirus 8 detection rate (P=0.0412). No significant changes in the titters of anti-human herpesvirus 8 IgG were observed. Treatment with human immunodeficiency virus-1 protease inhibitors is therefore associated with the clearance of human herpesvirus 8 DNA from peripheral blood of human immunodeficiency virus-infected patients. The concomitant decrease in the human immunodeficiency virus plasma load and increase in the peripheral CD4+ cell count suggest that an amelioration in the immune defect following reduction in the burden of human immunodeficiency virus-1 infection is responsible for the clearance of human herpesvirus 8 by protease inhibitors.

Adult↗

The prevalence and genetic diversity of hepatitis C infection in antenatal clinic attenders in two regions of England.

The prevalence and genetic diversity of hepatitis C infection in women attending antenatal clinics in two regions of England was investigated to inform future surveillance and control measures. Women booking into antenatal care are routinely offered a test for immunity to rubella. Serum residues from these tests were unlinked, anonymized and archived as part of the Unlinked Anonymous Prevalence Monitoring Programme (UAPMP). The serum specimens were tested for anti-HCV using a cost-effective pooling strategy. After taking into account differential sampling from the UAPMP serum archive, the adjusted overall prevalence of anti-HCV was 0.43% (95% CI: 0.32-0.53) in London and 0.21% (95% CI: 0.14-0.28) in the Northern and Yorkshire region. Restriction fragment length polymorphism of amplified HCV RNA identified type 3a as the most common HCV genotype in these antenatal women. The prevalence of anti-HCV in antenatal women in the UK is low and consistent with that expected from injecting drug use.

Adolescent↗

Hepatitis C virus-associated oral lichen planus: no influence from hepatitis G virus co-infection.

There is a variable geographic distribution in the prevalence of hepatitis C virus (HCV)-related oral lichen planus (OLP), which appears unrelated to either HCV genotype or HCV epidemiology. The present study investigated whether hepatitis G virus (HGV) co-infection may be a feature of patients with HCV-related OLP, which might explain these phenomena. HGV co-infection was detected in 6 of 39 Italian patients with HCV-related OLP, but the presence of HGV did not influence the clinical presentation of OLP. It is concluded that HGV co-infection is unlikely to influence the clinical detection of HCV-related OLP.

Adult↗

Selective transmission of hepatitis B virus after percutaneous exposure.

In 3 clusters of postsurgical hepatitis B virus (HBV) infection, HBV DNA sequence mismatches were observed between the transmitting surgeons and the patients whom they infected. Sequence analysis of clones amplified from the C gene of HBV suggested that the mismatches were due to transmission of a minority variant in the circulation of each surgeon. Compared with 5 other transmitters from whom transmission of the dominant variant was demonstrated, the 3 surgeons who transmitted minority variants carried significantly more heterogeneous HBV populations. Transmission of minority variants was not correlated with the transmitters' hepatitis B antigen status, the presence of the position 1896 precore mutant, or the level of HBV viremia. In 1 cluster, a variant comprising <10% of the HBV population circulating in the transmitting surgeon established infection in all 3 patients who acquired HBV through him, which substantiates the phenomenon of true selection.

Base Sequence↗

Characterization of a highly divergent TT virus genome.

A novel TT virus (TTV)-like DNA sequence was detected in the serum of a patient (PM) with acute non-A-E hepatitis. The full-length genome sequence, referred to here as PM virus (PMV), was obtained and its relationship to other full or near full-length TTV sequences examined. Although it shares a common genomic arrangement and short conserved regions, the majority of the genome is extremely divergent, displaying an average genetic distance of 0.60 from all other TTV sequences. By comparing PMV with TTV genomes representing the most divergent types so far described, six major groups can be distinguished. The level of genetic diversity seen between these genomes is higher than would be expected within a single virus species. Indeed, PMV could be considered the prototype of an independent taxonomic group within the Circoviridae: family. A genoprevalence study of sera from blood donors and patients with acute hepatitis suggests that PMV is rare.

DNA Virus Infections↗

The most prevalent hepatitis C virus genotypes in England and Wales are 3a and 1a.

Hepatitis C virus (HCV) genotypes were assigned to 567 individuals by restriction fragment length polymorphism analysis of the 5' noncoding region of the HCV genome following reverse transcription-polymerase chain reaction. The groups of individuals in this study included hemophilia patients, injecting drug users (IDUs), blood donors, antenatal patients, those attending genitourinary medicine (GUM) clinics, and patients with chronic liver disease, all from England and Wales. The majority of HCV infections were types 1a (32%), 1b (15%), or 3a (37%). The genotype distribution in individual groups was similar to the overall genotype distribution except for hemophilia patients, in whom the frequencies were 1a (39%), 1b (23%), and 3a (21%). With the exception of hemophilia patients, subpopulations in England and Wales appear to share common modes of HCV transmission. There is a need for continued surveillance to monitor the spread of possibly more virulent or drug-resistant HCV genotypes.

5' Untranslated Regions↗

Natural and iatrogenic variation in hepatitis B virus.

The existence of HBV as quasispecies is thought to be favoured by the infidelity of HBV RT, which would account for the emergence of the many natural mutants with point substitutions. RT infidelity may also underlie the hypermutation phenomenon. Indeed, the oft-reported point mutation in the preC gene that leads to failure of HBeAg synthesis may be driven by a hypermutation-related mechanism. The presence of mutants with deletions and insertions involving single nucleotides and oligonucleotides at specific positions in the genome, and of mutants with deletions of even longer stretches particularly in the C gene, suggests that other mutagenic mechanisms operate. Candidates include slippage during mispairing between template and progeny DNA strand, the action of cellular topoisomerase I, and gene splicing using alternative donor and acceptor sites. Natural substitutions, deletions or insertions involving the Cp/ENII locus in the X gene can significantly alter the extent of viral replicative activity. Similar mutations occurring at other locations of Cp/ENII, and at B-cell epitope sites of the S gene are associated with failure to detect serological markers of HBV infection. HBV variation can also arise from recombination between coinfecting strains. S gene mutations that become evident following HBIG administration and HBV vaccination are all point substitutions, as are mutations in functional RT domains of the P gene after treatment with viral RT-inhibitory drugs. Widespread and long-term use of prophylactic and therapeutic agents may potentially generate serologically occult HBV variants that might become difficult to eradicate.

Amino Acid Sequence↗

Tissue distribution of Epstein-Barr virus genotypes in hosts coinfected by HIV.

BACKGROUND: In healthy people, oral and pharyngeal epithelium preferentially carries Epstein-Barr virus (EBV) belonging to a genotype that possesses three copies of a 29 base-pair repeat in the first intron of the BZLF-1 gene, while peripheral blood mostly carries a genotype that bears two copies. Whether EBV shows differential tropism in HIV-1-coinfected hosts, who are prone to develop oral hairy leukoplakia, has not been studied. METHODS: Tongue scrapings and CD45+-enriched peripheral blood cells of 20 HIV1-infected patients and 40 healthy controls were examined. EBV-specific DNA was amplified from segments in the first intron of the BZLF-1 gene, in exon C of the LMP-1 gene, and the type A/B-specifying domain of the EBNA-3C gene. Size polymorphisms of these amplicons were assessed by agarose gel electrophoresis, and DNA sequence differences among BZLF-1 gene amplicons by single-strand conformation polymorphism analysis. RESULTS: The predominant EBV genotype in peripheral blood as well as tongue carried two copies of the BZLF-1 repeat. In controls, although the BZLF-1 genotype with two copies was exclusively detected in the blood, the genotype with three copies predominated in the tongue. The findings could not be correlated with EBV genotyped according size polymorphisms in the EBNA-3C or LMP-1 genes. DNA sequences of a proportion or all of the clones derived from the BZLF-1 amplicons in the tongues of HIV-1-infected patients were identical to those in the blood. CONCLUSIONS: These findings are consistent with EBV haematogenous superinfection of the tongue of HIV-positive individuals. Such superinfection may precede or lead to the development of oral hairy leukoplakia.

Blood Cells↗

No evidence of HCV infection or liver disease in British patients with oral lichen planus.

An association between chronic hepatic disease and/or hepatitis C (HCV) infection and lichen planus (LP) has been described in patients from Italy, Japan and Spain. There are no data on the frequency of the association with HCV in British patients. In the present investigation, the HCV seropositivity and liver function status of 55 British patients with oral LP were assessed and compared with these parameters in 110 healthy control subjects. None of the patients with LP or control subjects had serum IgG antibodies to HCV or had abnormal liver function. It was concluded that while LP may be associated with HCV infection and liver disease in some southern European and other patients, such a co-occurrence was not detected in British patients.

Adult↗

Hepatitis C in blood transfusion recipients identified at the Oxford Blood Centre in the national HCV look-back programme.

After the introduction in September 1991 of donor screening for hepatitis C, 95 potentially infectious blood donors who had given blood before this date were identified at the Oxford blood centre. Three hundred and ninety-nine blood components issued previously from these donors were identified in the course of the national HCV look-back programme. Of 399 questionnaires sent to hospital blood banks 392 were returned, identifying 290 recipients of whom 177 (61%) had died, and 113 (39%) were still alive 4-13 years after transfusion. One hundred and four recipients were traced and tested. Forty-nine recipients were not HCV infected. Forty-four of 58 (76%) recipients who received blood from donors found to be HCV RNA positive after September 1991 gave positive test results for HCV RNA. Eleven of 58 showed only antibody (anti-HCV), and 3/58 who had apparently received infectious blood showed no sign of past infection. The 11 who showed anti-HCV only, together with the three who showed no sign of past infection despite strong evidence of receiving HCV RNA-positive blood, had a mean age at transfusion of 27 years, compared with mean age at transfusion of 46 years in the 44 recipients with persistent HCV infection. Virus genotyping in 33/44 HCV RNA-positive recipients revealed five different genotypes. These did not seem to influence the outcome. Virus genotypes in 31 donor-recipient pairs showed complete concordance. Liver biopsies in 23/44 RNA-positive recipients showed minimal inflammation in four, mild in eight and moderate in 11. Liver fibrosis, Ishak grades 1-3, was present in 16/23 recipients. One other male recipient, not subjected to a liver biopsy, developed a hepatocellular carcinoma which caused his death at the age of 71, 8 years after transfusion.

Adolescent↗

Failed postnatal immunoprophylaxis for hepatitis B: characteristics of maternal hepatitis B virus as risk factors.

A retrospective case-control study was conducted to determine why some infants born full-term without obstetric intervention to hepatitis B e antigen (HBeAg)-seropositive mothers become infected by hepatitis B virus (HBV) despite having received passive-active immunoprophylaxis. Cases and controls comprised 12 hepatitis B surface antigen (HBsAg)-seropositive infants and 22 HBsAg-seronegative infants, respectively. Infants infected by putative vaccine-escape mutants were excluded. Risk factors, after adjustment for the level of maternal viremia, were the following allelic base changes in maternal HBV:C158, A328, G365, and A479 (P = .017, .005, .003, and .005, respectively). High-level maternal viremia (i.e., > or = 10(8) genome equivalents/mL) was a significant factor only after adjustment for G365 (P = .027). HBV DNA sequences recovered from one of the cases, the case's mother, and three infected contacts all had the high-risk mutations. Specific allelic mutations in maternal HBV and level of maternal viremia are potential predictors of vertical breakthrough infection.

Case-Control Studies↗

Diversity of naturally occurring Epstein-Barr virus revealed by nucleotide sequence polymorphism in hypervariable domains in the BamHI K and N subgenomic regions.

The extent of nucleotide sequence microheterogeneity varies among subgenomic regions of Epstein-Barr virus (EBV). We examined, in EBV-carrying lymphoid cell lines, the extent of polymorphism in EBV DNA fragments amplified from the BamHI E, K, N and Z regions, and then investigated the diversity of the more hypervariable regions in tissues and body fluids. In cell lines, sequence dissimilarities in a genotype-specifying fragment of the EBNA-3C gene varied from < 1-4% within each genotype; dissimilarities in the first intron of the BZLF- 1 gene were < 2% within each genotype. By contrast, dissimilarities in a C-terminal unique domain of the EBNA-1 gene, and in a fragment that encompasses and is upstream of the LMP-1 start codon, varied between 2 and 7% and were not genotype-specific. The sequence diversity in BamHI K and N regions was then examined in tissues and body fluids by single-strand conformation polymorphism (SSCP) analysis and cycle sequencing. Extensive inter-host diversity was observed, whether the host was co-infected by human immunodeficiency virus (HIV) or not. In the oral cavity of HIV-infected patients, inter-compartmental EBV diversity could be demonstrated, even between sites that were anatomically proximate. Studies of BamHI K clones derived from EBV in oral lesions revealed infection by multiple variants. Identification of hypermutable loci within the EBV genome such as those located in the BamHI K and N regions should permit fine discrimination of individual EBV variants.

Amino Acid Sequence↗

Fatal outcome of transmission of hepatitis B from an e antigen negative surgeon.

Investigation of the death of a 77 year old woman from acute hepatitis B infection revealed that she had undergone orthopaedic surgery two and a half months earlier. The surgeon was found to be a hepatitis B surface antigen carrier, hepatitis B e antigen (HBeAg)negative, but with antibodies to HBeAg. Viruses from the surgeon and the patient were identical, apart from a single nucleotide substitution. Both had a precore mutation, which prevents expression of e antigen. A look back exercise was undertaken on the patients operated on by the surgeon during the previous year. The surgeon had performed exposure prone procedures on 253 patients, 188 of whom provided blood specimens. No HBsAg carriers were detected, and no serological markers of recent transmission were found.

Aged↗

Human herpesvirus 8 variants in sarcoid tissues.

BACKGROUND: The cause of sarcoidosis is unknown, although mycobacteria have been implicated. We examined sarcoid tissues for human herpesvirus 8 (HHV-8) in addition to mycobacterial genomic sequences. METHODS: Biopsy samples from 17 patients with sarcoidosis were studied (eight transbronchial, 27 lymph node, two skin, and two oral mucosa). We used tissues (n = 137) from 96 patients without sarcoidosis as negative controls. A nested PCR was applied to amplify a segment of open reading frame (ORF) 26 of the HHV-8 genome, and a heminested PCR was to amplify a segment of ORF 25 of HHV-8 and of the 16 S rRNA gene of mycobacteria. Differences in base sequences of the amplified fragments were resolved with single-strand conformation polymorphism and dideoxy sequencing. FINDINGS: HHV-8 ORF 26 DNA was detected in significantly higher proportions of sarcoid than of non-sarcoid tissue samples from lung (8/8 vs 0/54; p < 0.0001), lymph nodes (26/27 vs 6/29; p < 0.0001), skin (2/2 vs 0/17; p = 0.006), and oral tissues (2/2 vs 1/13; p = 0.029). 31 (82%) of the 38 ORF 26 DNA-positive sarcoid specimens were also positive for ORF 25 DNA. For mycobacteria-like 16 S rRNA DNA, the proportion positive was significantly higher in sarcoid than non-sarcoid tissues for lymph node samples (11/27 vs 2/29; p = 0.003) but not for other tissues (lung 3/8 vs 22/54; skin 2/2 vs 15/17; and oral tissues 1/2 vs 0/13). Overall, the prevalence of HHV-8 ORF 26 sequences was higher in sarcoid tissues than in non-sarcoid tissues (p < 0.0001). When patients whose tissues were included in a masked phase of the study were treated as units of analysis, eight of eight sarcoidosis patients were positive for HHV-8 ORF 26 DNA, compared with three of 56 control patients (p < 0.0001); for mycobacteria-like sequences, three of eight sarcoidosis patients were positive, compared with four of 56 controls (p = 0.0464). The HHV-8 ORF 26 sequences, ten of which were unique, could be segregated into four groups according to peptide motifs. In seven of nine patients from whom biopsy samples were taken from various sites, different sequences were recovered. The mycobacterial sequences amplified from sarcoid tissues were also varied, but none was homologous to those of known species. INTERPRETATION: Variant HHV-8 DNA sequences are found in a wide range of sarcoid but not non-sarcoid tissues. Mycobacteria-like 16 S rRNA sequences are more frequently present in sarcoid lymph nodes and not in other tissue types, but do not indicate infection by a particular mycobacterial species.

Adult↗

Prevalence of HCV infection in health care workers of a UK dental hospital.

OBJECTIVE: To determine the prevalence of hepatitis C virus (HCV) antibodies in a group of dental health care workers (DHCW). DESIGN: Retrospective cross sectional study. SETTING: A UK dental hospital. SUBJECTS AND METHODS: The sera of 167 unselected DHCW were tested for the presence of IgG antibodies to HCV using two, third-generation enzyme-linked immunosorbent assays (ELISA). HCV viremia was determined by reverse transcription polymerase chain reaction (RT-PCR) analysis. RESULTS: Two (1.2%) of the serum samples were found to be anti-HCV positive; one was also viremic. The two antibody-positive subjects were a qualified dental nurse and a student dental nurse, both females, without any known risk factor for HCV acquisition. No dentist was HCV seropositive. CONCLUSIONS: Since the prevalence of HCV infection in the UK general population varies between 0.08% and 0.55%, these results suggest that DHCW, and auxiliary staff in particularly, may have a slightly increased risk of HCV infection.

Adolescent↗

Hepatitis B virus genomic heterogeneity: variation between quasispecies may confound molecular epidemiological analyses of transmission incidents.

Nucleotide sequence variability studies were conducted on a 263-base pair fragment of the core-coding genomic region of hepatitis B virus (HBV), amplified by the polymerase chain reaction (PCR) from three surgeons with varying circulating levels of HBV, all of whom were thought to have transmitted HBV to their patients post-surgically. DNA sequencing was applied to amplicons obtained directly from serum and those cloned into plasmid vectors, and from single HBV molecules in serum separated by a limiting dilution procedure. In one surgeon, who had a titre of approximately 3 x 10(5) genome equivalents ml-1, the direct sequence was identical to none of 29 other sequences and differed by one base substitution from the sequence amplified from the single patient he infected. In another surgeon, who had a titre of approximately 2 x 10(6) genome equivalents ml-1, the direct sequence was identical to 17 of 36 (47%) sequences; however, the sequence common to all three infected patients was identical to a unique sequence in the surgeon that differed by three base substitutions from the direct sequence. By contrast, the direct sequence in the third surgeon, who had a titre of approximately 4 x 10(7) genome equivalents ml-1, was identical to 25 of 38 (66%) sequences, and to the sequence common to all 11 infected patients. Assessment of HBV DNA sequences directly amplified from clinical specimens may not be appropriate to studies of transmission in which the source of infection harbours a relatively dilute, heterogeneous mix of viral variants.

Amino Acid Sequence↗