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Biomedical subjects

S Britton

Publications and source records attributed to S Britton.

At least 19 recordsLinked to original sources
PubMed1992

Response of Ethiopian human immunodeficiency virus type 1 isolates to antiviral compounds.

Human immunodeficiency virus type 1 (HIV-1) isolates of 8 Ethiopian and 8 Swedish untreated AIDS-patients were examined for their sensitivity to 3'-azido-3'-deoxythymidine (AZT), 2',3'-dideoxyinosine (ddI) and leukocyte-derived interferon-alpha (IFN-alpha). No significant difference in drug sensitivity was found between Ethiopian and Swedish isolates, which all were sensitive to AZT, ddI and IFN-alpha except for one Swedish isolate. This isolate exhibited a mutation at amino acid position 215. These results suggest that it should be possible to perform clinical trials in Ethiopia using the same dose regimens as in Sweden.

Acquired Immunodeficiency Syndrome↗
PubMed1992

Relationship between cell-free viraemia, antigenaemia and antibody levels in HIV-1-infected Ethiopian patients.

OBJECTIVE: To determine the relationship and occurrence of cell-free viraemia, free or immune-complexed p24-antigen and p24-antibody levels in blood from HIV-1-infected patients in Ethiopia. METHODS: Peripheral blood was obtained from 66 Ethiopian and 137 Swedish HIV-1-seropositive patients. Blood samples were analysed for free or immune-complex bound p24 antigen by enzyme-linked immunosorbent assay before and after acid hydrolysis of immune complexes for infectious virus in plasma and peripheral blood mononuclear cells (PBMC), and for p24-antibody levels. We compared the kinetics of viral replication of Ethiopian with Swedish isolates in vitro. RESULTS: Infectious virus was isolated from PBMC in 95% and from plasma in 81% of Ethiopian AIDS patients. In contrast, p24 antigen was detected in only 5% of AIDS patients from Ethiopia, compared with 76% of those from Sweden. p24-antibody levels were much higher and more persistent in Ethiopian than in Swedish subjects. The ratio between reverse transcriptase activity and p24 antigen was significantly higher in Ethiopian isolate culture than in those of the Swedish isolates. CONCLUSIONS: Our results show that relationships between viraemia, p24 antigenaemia and p24-antibody levels in HIV-1-infected Ethiopian patients differ from those found in comparable Swedish patients. This pattern may partly explain the differences seen in the natural course of HIV-1 infection in Ethiopia and Sweden.

Adult↗
PubMed1992

High HIV seroprevalence and increased HIV-associated mortality among hospitalized patients with deep bacterial infections in Dar es Salaam, Tanzania.

OBJECTIVES: To correlate deep bacterial infections with HIV infection and evaluate the influence of HIV on clinical picture and outcome in patients with meningitis, pneumonia or pyomyositis. DESIGN: Case-control comparison of HIV seroprevalence between patients and an age- and sex-matched control group in a prospective cross-sectional study of hospitalized patients. PARTICIPANTS: One hundred and sixty-five patients admitted to hospital with either purulent meningitis, pneumonia or pyomyositis and 165 age- and sex-matched controls from orthopaedic/trauma wards. SETTING: University Hospital, Dar es Salaam, Tanzania. OUTCOME MEASURES: Differences in HIV seroprevalence and mortality. RESULTS: Of 78 patients with purulent meningitis, 19 (24%) were HIV-seropositive, compared with 13 (17%) in the control group (P = 0.345). Of 36 patients with meningitis seen before a meningococcal epidemic affected Dar es Salaam, there was a statistically significant association with HIV infection (P = 0.013). Ten out of 19 (53%) HIV-seropositives died, compared with nine out of 59 (15%) seronegatives (P = 0.028). Of patients with pneumococcal meningitis, five out of six (83%) seropositives died, compared with two out of 12 (17%) seronegatives (P = 0.013). Fifteen out of 45 (33%) patients with pneumonia were HIV-seropositive, compared with four (9%) in the control group (P = 0.001). There was no difference in mortality between seropositive and seronegative patients with pneumonia. HIV seroprevalence was 62% among 42 patients with pyomyositis and 12% among 42 controls (P less than 0.0001). Eighteen out of 25 (72%) seropositive patients with pyomyositis fulfilled the World Health Organization (WHO) clinical case definition for AIDS. Response to recommended antibiotic treatment was satisfactory among patients with pneumonia and pyomyositis. CONCLUSIONS: These results show a strong association between pyomyositis, pneumonia and HIV infection. They also indicate an increased mortality associated with HIV infection in patients with pyogenic meningitis, especially pneumococcal meningitis. Pyomyositis should be considered an indicator of stage III HIV disease in the proposed WHO clinical staging system.

AIDS-Related Opportunistic Infections↗
PubMed1991

HIV-1 in Ethiopia: phylogenetic divergence from other HIV-1 strains.

Phylogenetic tree analysis was performed on selected polymerase chain reaction (PCR)-amplified and sequenced regions of the gag and env reading frames of several Ethiopian and Swedish human immunodeficiency virus type 1 (HIV-1) strains. These regions are considered to be conserved parts of the HIV-1 genome and correspond to the p7 of the core (gag) and part of the carboxy terminal of the gp41 protein of env respectively. Comparisons were made with all available HIV-1 sequences. The tree analysis showed that gag sequences from nine and env sequences from four Ethiopian strains all grouped together in separate branches distinct from all other sequenced European, North American, and African HIV-1 isolates. Thus, the Ethiopian strains seem to represent a highly divergent group of HIV-1, which might have developed during a relatively early stage of HIV-1 evolution.

Base Sequence↗
PubMed1991

Intracellular metabolism of 3'-azidothymidine in isolated human peripheral blood mononuclear cells.

Azidothymidine (AZT) inhibits the replication of human immunodeficiency virus and it is the only drug so far licensed for treatment of acquired immunodeficiency syndrome (AIDS). A prerequisite for its antiviral activity is phosphorylation by cellular nucleoside kinases to the mono-, di-, and triphosphate levels. This study determined the capacity of isolated peripheral blood mononuclear cells (PBMC), resting or mitogen stimulated, from 36 different people of whom 5 were HIV+, to phosphorylate and accumulate intracellular AZT nucleotides. We found a large variation in the amount of products formed between PBMC treated at different times from the same individual as well as between the PBMC from different individuals. Resting PBMC showed the largest interindividual variation and their levels of AZT nucleotides were about 60-150-fold lower than in activated PBMC. The intracellular half lives of azidothymidine mono-, di-, and triphosphates, constituting, on the average, 96-99.2, 0.7-1.8, and 0.4-2.7% of total nucleotides at 0.08-1.6 microM AZT, respectively, were also determined. In mitogen-stimulated PBMC it was approximately 2.5 +/- 0.6 h for all the azidothymidine metabolites. The half-life for intracellular azidothymidine monophosphate in resting PBMC from two individuals was determined to 1.5 +/- 0.2 h. There appeared to be no significant difference in the AZT metabolism in PBMC from HIV-positive or-negative persons. A relative decrease in the intracellular formation of AZTDP and AZTTP from AZTMP was observed at concentrations of AZTMP above 1 microM. This fact may explain why lowering the doses of AZT still gives therapeutically efficient levels of the active metabolite AZTTP.

Adult↗
PubMed1991

A hospital-wide outcome study.

Table 3 shows the summary of activity since the programme began in August 1990. Of the 8.4% of inpatients who were screened by the programme, 9% initiated some action. In the A&E Department, 1.1% of patients were screened and 10% of these resulted in action.

Hospital Bed Capacity, 100 to 299↗
PubMed1991

Prevalence of HIV-1 infection and symptomatology of AIDS in severely malnourished children in Dar Es Salaam, Tanzania.

In Dar es Salaam, Tanzania, 200 children with severe malnutrition and controls matched for age, sex, and area of residence were screened for serological evidence of infection with the human immunodeficiency virus type 1 (HIV-1) over 5 months in 1988. The prevalence of HIV-1 antibodies in the malnourished group was 25.5% (51 of 200) compared with 1.5% (three of 200) in the controls. The seroprevalence rate was equally high in malnourished children above the age of 18 months (26 of 102; 25.5%), as in those below this age (25 of 98; 25.5%). The prevalence rate was higher in children with marasmus (38.2%) as compared to children with marasmic-kwashiorkor (12.3%) or kwashiorkor (12.2%). The prevalence of clinical features known to be associated with AIDS was higher in the HIV seropositive malnourished children as compared to the seronegative children. The modified World Health Organization clinical case definition of AIDS in children was also evaluated and found to have a low sensitivity and positive predictive value (62.8 and 57.1%, respectively) but a fairly high specificity (83.9%). It is recommended to routinely rule out HIV infection in malnourished children, especially those with marasmus.

Acquired Immunodeficiency Syndrome↗
PubMed1990

Immune responses to fractionated cytomegalovirus (CMV) antigens after HIV infection. Loss of cellular and humoral reactivity to antigens recognized by HIV-, CMV+ individuals.

In order to delineate the molecular pathogenesis of the increased susceptibility to CMV disease in HIV infection, the patterns of antigen responsiveness in HIV-infected and non-infected individuals were investigated. CMV was fractionated by SDS-PAGE and electroblotted onto nitrocellulose. Lymphoproliferative responses of healthy HIV-, CMV+ individuals and HIV+, CMV+ asymptomatic patients to a whole CMV antigen preparation and to 20 fractions of nitrocellulose-bound CMV were then compared. Three fractions of approximate molecular weight of 130-165, 65-75, and 55-65 kD appeared to contain the major T cell stimulating antigens for HIV-, CMV+ individuals. A statistically significant depression of responses to fractions containing antigens in the ranges of 130-165 kD and 55-65 kD but not to whole CMV was seen in HIV+ individuals compared with controls. In healthy controls, the sum of the proliferative responses as measured by 3H-thymidine uptake to these three major fractions was approximately equal to the response to a whole CMV antigen preparation, whereas it was less than half of this response in five out of six HIV+ subjects. When antibody activities to CMV antigens were analysed by immunoblotting of sera from the two subject groups and also sera of ARC and AIDS patients, a selective loss of reactivity was revealed in 10 out of 19 HIV+ subjects to a band of 26-28 kD whereas all 15 HIV-, CMV+ controls recognized this band. Serum IgG and IgM values were both significantly higher in HIV+ individuals than in controls. These findings suggest that specific lesions in the repertoire of immune responsiveness to CMV antigens occur in HIV+ individuals.

Antibodies, Viral↗
PubMed1990

Serum antibody specificities to Leishmania aethiopica antigens in patients with localized and diffuse cutaneous leishmaniasis.

In order to characterize the antigenic determinants of Leishmania aethiopica, we have analysed by immunoblotting the antibody reactivity of leishmaniasis patients with either the localized (LCL) or diffuse (DCL) clinical forms of disease. In this study we have compared the reactivity of antibodies from eight LCL and DCL patients to parasites isolated from each individual, or the parasite isolates of the other LCL and DCL patients studied. The immunoblot profiles of antibodies from LCL patients differed from the antibody profiles of DCL patients. Serum antibodies from LCL patients showed limited recognition of somatic antigens of less than Mr 50,000 which were recognized by antibodies present in DCL patients. A direct comparison of individual LCL and DCL patient derived promastigotes determined that the lack of antibody to these antigens in LCL patients was not due to the differential expression of these determinants by the LCL and DCL derived promastigotes. The results of this study suggest that although either LCL or DCL derived promastigotes express a wide variety of antigenic moieties which are potentially reactive with antibodies, only a subset of antibodies against these specificities develop in any individual patient, during active infection.

Adolescent↗
PubMed1990

Differences in PCR reactivity between HIV proviruses from individuals in Ethiopia and Sweden.

The polymerase chain reaction (PCR), using primer pairs in the gag, pol, and env regions, was used in a comparative study of HIV-1 DNA in peripheral mononuclear blood cells from HIV-1-seropositive individuals in Ethiopia and Sweden. Although all Swedish samples were positive by PCR, the reactivity was more pronounced in samples from late stages than in those from early stages of infection. Six of nine Ethiopian samples from HIV-1-seropositive patients were positive by PCR, but the reactions were much weaker than those observed for Swedish samples, and in most cases seen with one primer pair only. These results suggest that the burden of HIV-1 DNA in peripheral mononuclear blood cells increases with advancing disease. PCR using primer pairs designed to detect HIV-1 infection in Europe and North America is not always suitable for the detection of HIV-1 infection in Ethiopia. The differences in PCR reactivity could possibly be a consequence of differences regarding host responses to the virus in the two countries, but more likely due to genomic differences between HIV-1 strains prevalent in Ethiopia and Sweden.

AIDS-Related Complex↗
PubMed1989

Persistent productive HIV infection in EBV-transformed B lymphocytes.

The susceptibility to HIV infection of 14 B-cell lines established from five healthy HIV seronegative and from six HIV seropositive subjects by lymphocyte transformation with EBV and/or by lymphocyte cultivation with cyclosporin A was studied. Although the cell lines contained different proportions of CD4-positive cells, as shown by flow cytometry, all of them could be infected with the SF-2 strain of HIV. Infection was blocked by a monoclonal antibody directed against the viral attachment site of the CD4 molecule, even in a line that lacked demonstrable CD4 receptors. B-cell lines with high proportions of CD4-expressing cells produced HIV p24 antigen more rapidly and at higher concentrations than cell lines with low CD4 expression. Although HIV infection resulted in some cytopathic effects, it was possible to cultivate the infected cells for more than 8 months without refeeding the cultures with uninfected cells. Even in long-term cultures, there was a continuous production of infectious HIV, as detected by transfer of culture supernatants to other susceptible cell lines. The production of viral antigens was consistently more pronounced in the B-cell line with the highest CD4 positivity than it was in a permissive T-cell line (HUT-78) infected in the same manner. These results indicate that HIV can chronically and productively infect transformed B cells via interaction with CD4 molecules. Thus it is possible that B cells may constitute a source of infectious virus in HIV-infected EBV-positive individuals.

Antigens, Differentiation, T-Lymphocyte↗
PubMed1989

Detection of cell-free human immunodeficiency virus in cerebrospinal fluid by using immune scanning electron microscopy.

The cerebrospinal fluid of 52 patients with human immunodeficiency virus type 1 (HIV-1) infection was incubated with polystyrene microspheres coated with monoclonal antibodies specific for HIV-1 core or envelope antigens. The beads were then collected on a filter surface and inspected by scanning electron microscopy (SEM). In 37 of 51 samples from subjects with chronic HIV-1 infection and from all three patients with primary HIV-1 infection, with or without neurologic symptoms, particles of 50-75 nm and 100-125 nm were visualized on beads coated with antibodies to HIV-1 core and envelope antigens, respectively. No such binding of particles was detected in the controls. Findings using immune SEM, which was found to be as sensitive as virus isolation, indicate that HIV-1 can replicate in the central nervous system (CNS) of patients with primary or chronic HIV-1 infection without causing neurologic symptoms. Production of cell-free virus seems to occur in the CNS of the majority of HIV-1-infected patients.

Acquired Immunodeficiency Syndrome↗
PubMed1988

Differential recognition of Leishmania aethiopica antigens by lymphocytes from patients with local and diffuse cutaneous leishmaniasis. Evidence for antigen-induced immune suppression.

Data are presented to suggest that differential Ag expression by parasites derived from diffuse (DCL) vs local (LCL) cutaneous leishmaniasis patients may be responsible for the Ag-specific anergy seen in DCL patients. The evidence suggests that promastigotes derived from DCL patients express epitopes which preferentially stimulate suppressor activities in DCL patients. These determinants appear to be expressed less, if at all by promastigotes derived from LCL patients. The Ag-specific suppression or nonresponsiveness which dominates the immune response in DCL patients during an active infection can be abrogated by drug treatment or removal of live DCL parasites, which suggests that Ag-induced regulatory cells, probably of T cell lineage, are most likely responsible for the nonresponsiveness seen in untreated DCL patients. Thus the mechanisms of immune regulation operating in this disease differ from that of lepromatous leprosy where the specific unresponsiveness (anergy) is irreversible even after successful treatment.

Animals↗
PubMed1988

Psychological factors influence the success of coronary artery surgery.

Thirty-six patients with angina were investigated by treadmill exercise testing and coronary angiography prior to coronary artery surgery. Severity of angina was judged by interview and self-assessment visual analogue scale and all patients were psychiatrically assessed. Further physical and psychiatric assessments were made at 3 and 6 months postoperatively. Eleven patients (31%) had significant psychiatric morbidity preoperatively and these had worse symptom scores and exercise tolerance compared with non-psychiatric cases, despite equivalent coronary angiographic findings and left ventricular function. Post-operatively, exercise tolerance improved equally in both groups but psychiatric cases remained significantly more symptomatic. Psychiatric morbidity remained unchanged throughout the study. We conclude that almost one third of patients with severe angina have psychiatric morbidity which is associated with a poor symptomatic response to coronary artery surgery, despite objective improvement in exercise tolerance. Ways of improving the symptomatic response to surgery in patients with coexisting psychiatric morbidity should be studied.

Adult↗