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Biomedical subjects

R S Tedder

Publications and source records attributed to R S Tedder.

At least 91 records · Page 5Linked to original sources

Hepatitis C antibody profile and viraemia prevalence in adults with severe haemophilia.

Sera from 21 patients who had received large amounts of unheated factor VIII concentrate were tested for antibodies to the hepatitis C virus (HCV) by both commercial (Ortho C100) and 'in house' ELISAs. 'In house' assays utilized recombinant structural (core) or non-structural (replicase) HCV proteins generated by a baculovirus expression system. Antibodies to HCV were detected in 100% of the sera by the core protein based ELISA but in only 62% and 19% by the C100 and replicase based ELISAs, respectively. Hepatitis C viraemia was demonstrated in 90% of the patients by in vitro amplification of the 5' non-coding region of the HCV genome. Amplification with primer sets from two other regions of the genome proved less efficient at detecting viraemia. We conclude that the prevalence of hepatitis C infection in haemophiliacs may have been underestimated previously and that almost all HCV-infected patients have evidence of on-going viral replication.

Adult↗

Demonstration of viraemia patterns in haemophiliacs treated with hepatitis-C-virus-contaminated factor VIII concentrates.

Sequential serum samples from previously untreated haemophiliacs in whom non-A, non-B hepatitis (NANBH) developed after they received factor VIII concentrate contaminated with hepatitis C virus (HCV) were tested by a commercial assay for the presence of antibodies to the C100 protein of HCV (anti-C100) and by "nested" PCR for the presence of HCV RNA sequences. Three temporal patterns of viraemia were observed: transient viraemia in acute resolving NANBH; viraemia lasting for several years in chronic NANBH; and intermittent viraemia in chronic NANBH, with an initial transient phase followed by recurrence after many months. In three of five cases the initial detection of serum HCV RNA was made before the onset of liver function test abnormality, many weeks or months before anti-C100 seroconversion. Diagnosis of acute HCV infection may therefore be possible much earlier by PCR than by existing serological techniques, but the timing of samples may be critical.

Acute Disease↗

Adult T-cell leukaemia/lymphoma in Brazil and its relation to HTLV-I.

In a series of fourteen patients with adult T-cell lymphoma-leukaemia (ATLL) in Brazil the main features were lymphadenopathy, hepatosplenomegaly, hypercalcaemia, and high leucocyte counts, with abnormal lymphoid cells which had irregular nuclei. The series included the youngest patient with ATLL so far (18 months). Analysis with monoclonal antibodies showed a mature T-cell phenotype (CD4+, CD8-). Antibodies to HTLV-I and/or integration of HTLV-I proviral DNA were found in eleven patients. In the other three HTLV-I DNA could not be demonstrated even by means of the polymerase chain reaction; they therefore had HTLV-I-negative ATLL. This report of ATLL in Brazil corroborates serological reports that HTLV-I may be endemic in some parts of that country. Follow-up studies are required to identify precisely the main route of transmission of HTLV-I in South America and the risk factors for the development of ATLL in carriers.

Adult↗

Human herpesvirus 6 in salivary glands.

In an investigation of the role of saliva in the transmission of human herpesvirus 6 (HHV6) sections of salivary gland tissue were screened for HHV6-specific DNA by in-situ hybridisation and for HHV6-specific protein by immunohistochemical staining with monoclonal antibodies against the virus. All of nine submandibular glands and one of four parotid glands showed the presence of HHV6 genome and expressed protein by these techniques. The findings are consistent with transmission of HHV6 by saliva and suggest that salivary gland tissue is a site of replication of the virus and a potential site for HHV6 persistence.

DNA, Viral↗

Detection of hepatitis C viral sequences in blood donations by "nested" polymerase chain reaction and prediction of infectivity.

Of 1100 blood donations tested during a prospective study of post-transfusion non-A, non-B hepatitis (NANBH), 6 (0.55%) were repeatedly reactive in a commercial assay for antibodies to the C100 protein of hepatitis C virus. Only 1 of the 6 donations (17%) transmitted NANBH to a recipient. Hepatitis C virus RNA sequences were detected in the serum of the transmitting donor by an assay which used the polymerase chain reaction (PCR) and non-radioisotopic detection. No such sequences were detected in the other 5 donors positive for anti-C100. Stored serum samples from blood donors who had been involved in three episodes of post-transfusion NANBH in 1981 also contained hepatitis C viral sequences. Although the PCR assay in its present form is not suitable for mass donor screening, the presence of hepatitis C viral sequences detected by PCR in blood donations seems a better predictor of infectivity than the presence of anti-C100 alone.

Antigens, Viral↗

Prevalence of maternal HIV infection based on unlinked anonymous testing of newborn babies.

This pilot study established that unlinked anonymous testing of dried blood spots routinely collected on Guthrie cards for neonatal screening is a feasible method for monitoring HIV prevalence in women at the time of delivery. The method was sensitive, specific, and less expensive than more conventional ELISAs. 114,515 dried blood spots taken from cards collected in three Thames regions were tested for antibody to HIV-1. 28 samples were confirmed to be antibody positive by western blot (seroprevalence 0.24 per 1000). Unlinked anonymous screening of newborn babies should be extended to monitor the spread of HIV infection in the heterosexual population and to target preventive strategies and provision of health care.

Agglutination Tests↗

Detection of hepatitis B virus antigens in liver tissue. A relation to viral replication and histology in chronic hepatitis B infection.

The expression of hepatitis B virus antigens was studied by double staining liver tissue with appropriate antisera and correlated with serum hepatitis B viral DNA and histology in 28 patients with disease related to chronic hepatitis B virus infection. The cellular localization of hepatitis B core and hepatitis B e antigens generally coincided, but there were important differences at a subcellular level. Thus, hepatitis B e antigen was detected in nuclei and/or cytoplasm but strong cytoplasmic hepatitis B e antigen was associated with a high serum hepatitis B viral DNA (P = 0.0017) but not with active liver disease. Hepatitis B core antigen could also be detected in nuclei and/or cytoplasm, but strong cytoplasmic hepatitis B core antigen expression, exceeding that of hepatitis B e antigen, was associated with active liver disease (P = 0.041) and not with serum hepatitis B virus DNA. The proportion of hepatocytes expressing hepatitis B surface antigen correlated inversely with the serum titer (P = 0.0017), whereas hepatitis B surface and nucleocapsid antigens were usually expressed independently. The data support the hypothesis that cytoplasmic hepatitis B core antigen and not hepatitis B e antigen is the target for immune system-mediated cytolysis of hepatocytes. Cytoplasmic hepatitis B e antigen is not associated with liver damage but is instead associated with high levels of hepatitis B virus replication.

Antibodies, Monoclonal↗

Production of IgM antibody to HHV6 in reactivation and primary infection.

The cross-reaction of HHV6 antibody with that to the other herpesviruses was studied in 96 blood donors whose sera were tested for IgG antibody to human herpesvirus type 6 (HHV6), cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella zostervirus (VZV) and herpes simplex virus (HSV). No correlation was found between IgG antibody to HHV6 and that to any of the other herpesviruses in these individuals. Antibodies to HHV6 and CMV were measured in patients undergoing documented serological responses to HHV6. Eleven cases of primary HHV6 infection associated with roseola infantum in babies, 1 of whom suffered from gastroenteritis as well as pyrexia and rash, are reported. Three cases of HHV6 reactivation, 1 in a 3-year-old child and 2 in adults, 1 of whom simultaneously underwent a primary CMV infection are also reported. Our results suggest that indirect immunofluorescence is a specific way of measuring HHV6 antibody, that HHV6 IgG and IgM can be detected in the absence of antibody to CMV and that HHV6 IgM is present both in primary HHV6 infections and in reactivations.

Adult↗

Response of serum p24 antigen and antibody to p24 antigen in patients with AIDS and AIDS-related complex treated with zidovudine.

In an open study of the treatment of patients with AIDS-related complex (ARC) and AIDS with zidovudine, we evaluated the response of serum p24 antigen (p24Ag) and antibody to p24Ag (anti-p24) levels. Before treatment, serum from 49 out of 73 (67%) patients was p24Ag-positive, and of these patients 42 received zidovudine 800-1200 mg daily for greater than 4 weeks and had a baseline mean serum level of p24Ag of 119 pg/ml (s.e. 15.7). On zidovudine there was a reduction of p24Ag to 21.12% (s.e. 4.76) of pretreatment values at 3 months; however, there was a subsequent trend for levels after 6 months to increase to greater than 50% of pretreatment levels at 12 months. Serum levels of anti-p24 were measured in 26 patients. Of 16 patients whose serum contained p24Ag and 10 whose serum did not, four and nine, respectively, had detectable levels of anti-p24. There was no significant change in the serum anti-p24 with zidovudine therapy.

AIDS-Related Complex↗

Cytomegalovirus and human herpesvirus-6 in sudden infant death syndrome: an in situ hybridization study.

Thirty lung, spleen, and thymus sections and four lymph node sections from 40 sudden infant death syndrome (SIDS) cases were probed with biotinylated DNA probes specific for human herpesvirus-6 (HHV-6) and cytomegalovirus (CMV). Control material gave a strong, distinct signal with little or no background staining and no cross-reactivity. No staining was found with the SIDS material. We find no evidence to implicate an overwhelming infection by either virus in SIDS.

Cytomegalovirus Infections↗

Human immunodeficiency viruses in patients attending a sexually transmitted disease clinic in London, 1982-7.

OBJECTIVE: To determine the prevalence of infection with the human immunodeficiency virus (HIV) in all patients attending a London sexually transmitted disease clinic over four weeks at the end of 1987 and to see how it varied from that in similar samples studied between 1982 and 1986. DESIGN: Anonymous testing of serum samples from consecutive heterosexual and homosexual patients having routine serological investigations for syphilis. Testing was for anti-HIV-I, anti-HIV-II, and hepatitis B core antibody (anti-HBc) and P24 antigen. Age, nationality, sexual orientation, and past sexually transmitted diseases were recorded for each patient. Gonorrhoea rates by quarters were analysed among homosexual and bisexual men and heterosexual men and women from 1981 to 1987. SETTING: Outpatient department of genitourinary medicine. PATIENTS: A total of 1074 patients attending consecutively for syphilis serology. Thirty five homosexual and bisexual men were excluded (these were regular attenders as part of a prospective study of the natural course of HIV infection). MEASUREMENTS AND MAIN RESULTS: The prevalence of anti-HIV-I in homosexual and bisexual men in 1987 was 25.6% (64/250). Results in the same clinic population between 1982 and 1984 had shown a rise in prevalence, which flattened out in 1985-6 and continued at that level. Among heterosexual attenders in 1987 the prevalence of anti-HIV-I was 1% (women 4/412; men 4/377), which contrasted with a prevalence of 0.5% (women 2/395; men 3/757) in January 1986. One homosexual man was seropositive for anti-HIV-II and seronegative for anti-HIV-I. Among homosexual and bisexual men the rate of gonorrhoea had declined by an average of 2.7% a year since 1981, such that by 1987--and for the first time in the clinic--there was no significant difference in the rates between these men and heterosexual men and women. CONCLUSIONS: The appearance of HIV-I infection among heterosexuals indicates a need for more aggressive education programmes and intervention strategies along the lines adopted for homosexual men. Surveillance for HIV-II infection is needed to provide information for future policy in national screening programmes.

Acquired Immunodeficiency Syndrome↗

Epitope location of 13 anti-gag HIV-1 monoclonal antibodies using oligopeptides and their cross reactivity with HIV-2.

A series of 15-mer oligopeptides which overlapped by five amino acids (AA) across the p24 of HIV-1SF2 and a similar series across the p18 of HIV-1SF2 were used to identify the locations of 13 anti-gag monoclonal antibodies (MAbs). Three anti-p24 MAbs recognized sequences within the first 50 AA of the amino-terminal. Another anti-p24 recognized a conformational epitope in the centre of the protein and this MAb cross-reacted with two HIV-2 isolates suggesting conservation of this epitope between HIV-1 and HIV-2. One anti-p24 MAb recognized a linear sequence in the carboxy-terminal 100 AA and one p24 antibody was assumed to recognize a truly conformational epitope as it did not react with any of the linear peptides. Four anti-p18 MAbs were located at the carboxy-terminus of p18 with another MAb mapping slightly inwards from the carboxy-terminus and one anti-p18 MAb failed to bind to the p18 peptides. The carboxy-terminal distribution of the p18 MAbs indicated a highly immunogenic nature for this region in mice. None of the anti-p18 MAbs showed cross-reactivity with HIV-2 isolates, confirming the greater sequence variability of p18 over p24.

Amino Acid Sequence↗