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Biomedical subjects

R S Tedder

Publications and source records attributed to R S Tedder.

At least 127 records · Page 7Linked to original sources

How sensitive are the commercial assays for anti-HTLV III/LAV?

The sensitivity of nine commercial assays, Western blot, and a newly developed monoclonal antibody-based assay for antibody to human T lymphotropic virus type III/lymphadenopathy associated virus (anti-HTLV III/LAV) were evaluated using a panel of mainly weak-positive sera. In tests on 20 sera three commercial assays and a monoclonal-based assay, representing two different solid-phase methodologies, were found to be more sensitive than Western blot. Our findings suggest that Western blot cannot be depended upon as the sole confirmatory test for anti-HTLV III/LAV. The continued use of the more sensitive enzyme-linked immunosorbent assays (ELISAs), particularly those of dissimilar methodology, would be a more valid approach to confirmatory testing.

Acquired Immunodeficiency Syndrome↗

Human immunodeficiency virus (HIV) infection in the regular sexual partners of homosexual men with AIDS and persistent generalised lymphadenopathy.

Thirty-five homosexual men who had been the regular sexual partners (for at least 6 months) of anti-HIV-positive patients with AIDS (N = 18) or PGL (N = 17) were studied. Twenty-one (60%) were seropositive, but 14 (40%) were consistently anti-HIV-negative. The duration of relationship with the index case was not statistically different in seropositive compared to seronegative partners; median 26 months (range 7-60) vs 30 months (range 7-60). However, seropositive partners had a significantly higher monthly number of other sexual partners and sexually transmitted diseases and a higher frequency of insertive and receptive anal intercourse in the preceding five years. The risk of acquiring HIV infection was significantly increased by frequent receptive anal intercourse when the frequency of insertive was controlled for but not the converse. Seronegative partners had undetectable antibodies by live and fixed cell immunofluorescence and by radioimmunoprecipitation and were repeatedly negative by competitive enzyme immunoassay. Furthermore, the sera of seronegative partners lacked HIV neutralising activity. Peripheral blood mononuclear cells (PBMCs) from seronegative partners, stained with monoclonal antibodies to seven different CD4 epitopes, revealed no differences when compared to those from heterosexual controls and no qualitative differences from cells from seropositive individuals. In addition, PBMCs from seronegative partners could be productively infected by HIV in vitro. If resistance to infection in seronegative partners exists, then it is likely that mechanisms other than a specific humoral immunity or CD4 polymorphisms are involved.

AIDS-Related Complex↗

Characterization of monoclonal antibodies against the human immunodeficiency virus (HIV) gag products and their use in monitoring HIV isolate variation.

Monoclonal antibodies were raised against the gag proteins of a British isolate of the human immunodeficiency virus (HIV), CBL-1. Seven of the monoclonal antibodies recognized HIV gag-coded proteins of 55,000 mol. wt. (p55) and 24,000 mol. wt. (p24), three recognized p55/p18 and three p18 alone. Cross-competition assays suggested that at least two independent epitopes exist on the p24 cleaved from the p55 precursor, whereas a cluster of closely related epitopes was recognized by the p55/p18 and p18 antibodies. The panel of monoclonal antibodies was then used to compare by immunofluorescence the expression of gag-encoded antigenic determinants on HIV isolates from different geographical locations. Minor changes in epitope expression were observed in isolates from the U.S.A. and Haiti with the most notable changes being detected in isolates from Zaire, Tanzania and Uganda.

Africa↗

Retrovirus infections among patients treated in Britain with various clotting factors.

At the end of 1984 a collaborative survey was carried out to determine the prevalence of infection with human T cell lymphotropic virus type III/lymphadenopathy associated virus (HTLV-III/LAV) and HTLV-I among 584 recipients of various blood products in Britain at that time. In 204 cases yearly point prevalence figures for infection were also obtained for 1978 to 1983. In 1984, 215 of 315 patients (68%) who had received commercial concentrate for haemophilia A were identified as positive for anti-HTLV-III/LAV as compared with only 18 of 166 patients (11%) given British concentrate alone for this disease. This difference was further emphasised by the yearly point prevalence rates: seroconversion began in 1980 among recipients of commercial concentrate, but not until 1983 did such an instance occur among recipients of British concentrate. Any conclusions must remain speculative, but possibly seropositivity among haemophiliacs may not carry so grave a prognosis as previously thought.

Blood Coagulation Factors↗

Human and monoclonal antibodies to hepatitis B core antigen recognise a single immunodominant epitope.

Monoclonal antibodies were raised against hepatitis B core antigen (HBcAg) synthesized in Escherichia coli. They identified a single immunodominant determinant on both liver-derived and E. coli-derived HBcAg. Cross-inhibition studies demonstrated that HBsAg-containing human sera which contained antibodies to HBcAg (anti-HBc) together with either hepatitis B e antigen (HBeAg) or its antibody (anti-HBe) essentially only recognised the same single determinant as the murine antibodies. The identification of a single dominant HBcAg determinant may be important if future hepatitis B virus vaccines contain HBcAg.

Animals↗

A pilot study of BW A515U (6-deoxyacyclovir) in chronic hepatitis B virus infection.

BW A515U (6-Deoxyacyclovir) is a pro-drug of acyclovir and almost 100% is absorbed orally. 250 mg orally 6-hourly for 10 days was given to 4 hepatitis B surface antigen/e antigen-positive carriers. No consistent effect on productive viral replication, as determined by serum DNA polymerase and DNA levels was observed. The changes that occurred in these markers and transaminases in 1 patient were attributed to a spontaneous depression of productive viral replication.

Acyclovir↗

HTLV-III antibody and T-cell subset ratios in haemophiliacs and their spouses.

44% of 63 British patients with either haemophilia A or B were HTLV-III antibody positive (HTLV-VIII+). HTLV-III+ was more frequent in high factor VIII concentrate users and 75% of severely affected haemophilia A patients were HTLV-III+. All eight patients who were exposed to factor IX concentrate were HTLV-III-. 17 haemophilia A patients who received only British made factor VIII concentrate (average 12,000 units/year) were HTLV-III-. Two of 63 patients had evidence of a pre-AIDS type symptom complex and both were HTLV-III+. Information from a cohort of 21 Liverpool haemophiliacs suggests that HTLV-III was first introduced into this country in 1981. OKT4/T8 ratios were abnormal in 52% of 21 patients studied but this finding was not confined to either HTLV-III+ or HTLV-III- individuals. The spouses of 14 HTLV-III+ haemophiliacs were all HTLV-III-.

Adolescent↗

Acute encephalopathy coincident with seroconversion for anti-HTLV-III.

Acute encephalopathy was associated with the appearance of antibodies to human T-lymphotropic virus (HTLV-III) in two patients. A third patient showed seroconversion for anti-HTLV-III, but the temporal association was not established so precisely. The illness was characterised by a prodromal period of up to 2 weeks, characterised by pyrexia, general malaise, and changes of mood. The encephalopathy culminated in epileptiform seizures in two of the patients. Electroencephalographic changes were compatible with viral encephalitis, and cerebrospinal-fluid pleocytosis was minimal. Neurological signs and symptoms resolved quickly in all patients, and no residual central-nervous-system sequelae were apparent.

Acquired Immunodeficiency Syndrome↗

Slim disease: a new disease in Uganda and its association with HTLV-III infection.

A new disease has recently been recognised in rural Uganda. Because the major symptoms are weight loss and diarrhoea, it is known locally as slim disease. It is strongly associated with HTLV-III infection (63 out of 71 patients) and affects females nearly as frequently as males. The clinical features are similar to those of enteropathic acquired immunodeficiency syndrome as seen in neighbouring Zaire. However, the syndrome is rarely associated with Kaposi's sarcoma (KS), although KS is endemic in this area of Uganda. Slim disease occurs predominantly in the heterosexually promiscuous population and there is no clear evidence to implicate other possible means of transmission, such as by insect vectors or re-used injection needles. The site and timing of the first reported cases suggest that the disease arose in Tanzania.

Acquired Immunodeficiency Syndrome↗

Human T-lymphotropic virus type III (HTLV-III) infection in seronegative haemophiliacs after transfusion of factor VIII.

Fifteen haemophiliac patients acquired antibodies to human T-lymphotropic virus type III during 1984. One batch of factor VIII concentrate given to all these patients is presumed to be the cause of the seroconversion. A further eighteen patients who received the same batch did not seroconvert and one other patient became seropositive but had not received this batch. Before transfusion of the implicated batch the patients had low T-helper-cell numbers and T-helper/suppressor ratios; neither changed in those who seroconverted. The probability of seroconversion was independently related to the pre-existing low T-helper/suppressor ratio, the number of vials of the implicated batch transfused, and the total annual factor VIII consumption. Ten other patients received a batch of factor IX concentrate from the same donor plasma; none of these patients seroconverted.

Acquired Immunodeficiency Syndrome↗

HTLV-III serology distinguishes atypical and endemic Kaposi's sarcoma in Africa.

Serum samples from African patients with Kaposi's sarcoma and acquired-immuno-deficiency-syndrome-related (AIDS-related) disorders and from normal subjects in Uganda and Zambia were tested for antibodies to the human T-lymphotropic retroviruses (HTLV) types I, II, and III. Nearly 90% of patients with AIDS-related disorders or with atypical, aggressive Kaposi's sarcoma were seropositive for HTLV-III in both countries, whereas only 17% of patients with classic endemic Kaposi's sarcoma were seropositive. Among the controls 20% were seropositive for HTLV-III in Uganda but only 2% in Zambia. None of the subjects tested had antibodies to HTLV-I or HTLV-II. These results are further evidence of the emergence of a clinically atypical form of Kaposi's sarcoma in Africans, which resembles that seen in American patients with AIDS, and which is associated with HTLV-III infection. The low frequency of antibodies to HTLV-III in the normal Zambian population together with the first appearance of HTLV-III-associated diseases during the past 2 years suggests that this virus is new to Zambia, although it may have been present in Uganda for longer.

Acquired Immunodeficiency Syndrome↗

Detection of both hepatitis B e antigen and antibody in a single assay using monoclonal reagents.

Monoclonal antibodies raised against HBeAg were used to develop a HBeAg and anti-HBe detection assay. Monoclones containing anti-HBe were used both for the coating of the solid phase and for the fluid phase label in a sandwich type assay. The percentage binding of 125I-labelled anti-HBe to serum HBeAg was much greater than that seen in a similar assay using only polyclonal reagents. Therefore it was possible to add a small quantity of HBeAg for neutralising any anti-HBe present in a test serum without affecting HBeAg detection. This small amount of serum HBeAg was incorporated into each test sample thus allowing the determination of the e status of a patient using only one aliquot of test serum. This single test assay could be performed either as a radioimmunoassay or as an ELISA. The sensitivity of these assays was found to be greater than the conventional polyclonal assay particularly with regard to sera containing anti-HBe.

Animals↗