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Biomedical subjects

S Bennett

Publications and source records attributed to S Bennett.

At least 145 records · Page 8Linked to original sources
PubMed1993

Immunoglobulin M and G antibody responses to Plasmodium falciparum glutamate-rich protein: correlation with clinical immunity in Gambian children.

The aims of the present study were to describe the age-related immunoglobulin M (IgM) and IgG response to part of a 220-kDa glutamate-rich protein (GLURP) from Plasmodium falciparum and to determine possible correlations of possession of these antibodies with malaria morbidity. IgM and IgG levels were measured with a recombinant fusion protein consisting of the carboxy-terminal 783 amino acids of the GLURP. Samples for the study were obtained during a longitudinal malaria morbidity survey performed in The Gambia; cross-sectional surveys were performed at the beginning of the transmission season in May and in October. Seropositivity rates increased with age to a maximum of 77% for IgM and 95% for IgG in adults. High prevalences of seropositivity were associated with certain human leukocyte antigen class II alleles (DRw8, DR9, DR7, DR4, DQw7, and DQw2) or haplotypes. The relationship between anti-GLURP489-1271 antibodies and clinical immunity is not clear; asymptomatically infected children aged 5 to 8 years had significantly higher levels of IgG than clinically ill children of the same age, suggesting that antibodies to the carboxy-terminal part of the GLURP may contribute to immunity to P. falciparum. However, this was not significant for younger children.

Adolescent↗
PubMed1993

Within-person variation in urinary sodium, potassium and creatinine concentrations, and their relationship to changes in the blood pressure of adult male Gambians.

Variation in urinary electrolyte and creatinine concentrations was studied in untimed, casual specimens obtained from 65 adult Gambian males over a 15-month period during which up to nine specimens were obtained from each subject. Measurements of blood pressure were made at the times when specimens were collected. The within-person variation in urinary creatinine, sodium and potassium concentrations were all found to be larger than that between persons. Within individual subjects, the sodium concentration tended to be comparatively low, and the potassium concentration high, in specimens in which the creatinine concentration was high. This suggests that the excretion of sodium was reduced at times of relative dehydration while the excretion of potassium may have been unrelated to the urine flow. The data also suggest that changes in the state of hydration were associated with changes in blood pressure since an individual subject's pressure was inversely related to the creatinine concentration. The negative relationship of the sodium:potassium ratio with creatinine concentration casts doubt on the simple use of this ratio as an indicator of dietary intake. After adjusting for creatinine concentration by multiple regression, changes in systolic pressure were shown to be positively correlated with changes in sodium concentration. These observations show the importance of replicating measurements of urinary electrolyte concentrations. The demonstration of complex inter-relationships between blood pressure and urinary concentrations of creatinine, sodium and potassium emphasizes the need for care in the interpretation of findings from causal, untimed urine specimens.

Adult↗
PubMed1992

Monocyte proliferation in a cytokine-free, serum-free system.

The aim of this study was to establish a cytokine-free, serum-free system which would enable the long-term survival and proliferation of human peripheral blood monocytes. Monocytes were isolated from peripheral blood mononuclear cells (PBMC) by adherence to untreated plastic petri dishes and maintained up to 6 weeks in serum-free medium (SFM) consisting of IMEM, insulin, transferrin, sodium selenite and BSA. Maximal cell proliferation occurred during the first 2 weeks of culture and corresponded to the appearance of large numbers of pure, nonadherent culture-derived macrophages. Monocyte maturation was characterised by the modulation of specific cell surface antigens. The percentage of cells staining for the transferrin receptor increased with time, whereas the percentages of cells expressing CD11b, CD11c and HLA-DR remained greater than 60% for the 15 days studied. The mean fluorescent intensities (MFI) of all these antibodies increased significantly with time. The only differences found between the adherent and nonadherent cells, using the above antibodies, were with the MFI for CD11b and CD11c. In both cases, the intensity of staining was significantly greater in the adherent cells. Estimation of cytokine production by cells maintained for 5 weeks in SFM found that they constitutively produced large amounts of macrophage colony-stimulating factor (M-CSF) in the absence of any exogenous stimuli. These cells were also found to secrete high levels of tumor necrosis factor-alpha (TNF-alpha) and interleukin-6 (IL-6) during the 1st week and granulocyte macrophage colony-stimulating factor (GM-CSF) during the 3rd week. However, the addition of exogenous GM-CSF (5 U/ml, S5) was found to significantly inhibit monocyte proliferation up to 17 days. This is the first report of proliferation associated with long-term survival of culture derived macrophages in a serum-free, cytokine-free system.

Antigens, Surface↗
PubMed1992

The statistical analysis of data from immunoepidemiological studies.

Immune responses encountered in human populations display a higher level of heterogeneity than is typically seen with laboratory animals, and the expected clear distinction between responders and non-responders to particular antigens may not be apparent. In such a situation, the methods of statistical analysis traditionally used in laboratory studies may no longer be appropriate, and there is no consensus among immunologists about how such data should be analysed. Using data from a large study of lymphocyte proliferation responses to candidate antigens for a vaccine against Plasmodium falciparum malaria, we discuss questions such as the appropriateness of logarithmic transformation of the data, the use of the stimulation index versus delta--cpm, the use of the proportion of responders for comparing two groups of individuals, and the choice of threshold for defining such a responder.

Animals↗
PubMed1992

Adjustments to the Mantel-Haenszel test for data from stratified multistage surveys.

The usual form of the Mantel-Haenszel test statistic assumes independent observations. This is inappropriate for data from a stratified multistage survey. Two alternative adjustments to the test statistic are developed to deal with this: (a) a modification of the effective sample size for each row of each table, using the design effects, extending a method proposed by Donald and Donner for familial aggregation studies; (b) a Taylor series approximation to the variance of the square root of the numerator of the Mantel-Haenszel statistic. Both methods are evaluated by application to both simulated and real data. The two methods perform equally well, and offer a considerable improvement over the unadjusted test statistic when observations from the same cluster are highly correlated. A simplified adjustment is also considered, as is the need for correction to the variance of the odds ratio estimator.

Chi-Square Distribution↗
PubMed1992

MHC and malaria: the relationship between HLA class II alleles and immune responses to Plasmodium falciparum.

In mice, immune responses to subunits of defined malaria antigens are regulated by genes mapping within the MHC and it has been suggested that such genetic restriction will be a major obstacle in the development of a human malaria vaccine. The relationship between class II human leukocyte antigen (HLA) genes and immune recognition of three candidate antigens for a vaccine against Plasmodium falciparum malaria has been investigated in a human population living in a malaria endemic area of West Africa. The study population was shown to be extremely heterogeneous for HLA class II alleles and marked differences in allelic frequency were detected between members of different ethnic groups. One class II DQA-DQB combination (serological specificity DQw2) was particularly common among members of the Fula ethnic group. This haplotype was significantly associated with higher than average levels of antibody to a peptide epitope, (EENV)6, of the malaria antigen Pf155/RESA. There was little evidence of association between HLA class II genotype and cellular proliferative or interferon gamma responses to the antigens tested. Overall, the number of significant associations between immune responses and specific HLA class II haplotypes was greater than would be expected by chance but less than would be expected if class II-dependent genetic restriction were a major factor governing human immune responses to malaria antigens. Thus, although some qualitative variation in the immune response to vaccine antigens may occur in ethnically different target populations, widespread HLA-associated nonresponsiveness to a multivalent subunit malaria vaccine is unlikely.

Adolescent↗
PubMed1992

Naturally acquired cellular and humoral immune responses to the major merozoite surface antigen (PfMSP1) of Plasmodium falciparum are associated with reduced malaria morbidity.

We have investigated the pattern of acquired immune responses to the major surface protein of Plasmodium falciparum merozoites (gp 190, PfMSP1) in a malaria endemic population in West Africa. A prospective longitudinal study in 3- to 8-year-old children was conducted to examine the relationship between naturally acquired immune responses to PfMSP1 and subsequent susceptibility to malaria infection and clinical disease. A population cross-sectional survey was performed to investigate changes in immune response with age. The prevalence and concentration of antibodies to all regions of the molecule increased with age with the highest prevalence of antibodies being detected against regions of the molecule which are highly conserved between parasite isolates. In vitro lympho-proliferation and interferon-gamma production in response to recombinant proteins representing polymorphic regions of the molecule also increased with age. Interestingly, proliferative responses to some regions of the molecule, including some highly conserved sequences, were highest in young children and decreased markedly with increasing age. Significant associations were observed between antibody and lymphoproliferative responses to proteins from the C terminus of the molecule and resistance to episodes of fever associated with high parasitaemia in partially immune children. In addition, high concentrations of antibodies to a conserved region close to the N terminus of PfMSP1 were also significantly associated with protection.

Africa, Western↗
PubMed1992

Shyness and education: the relationship between shyness, social class and personality variables in adolescents.

The study considers the relationship between shyness, some related personality variables and socio-economic status. Adolescent shyness levels are examined using two self-report questionnaires which cover the spectrum of inherent, emotional and situational shyness. These findings were correlated with individual levels of anxiety, neuroticism and also with socio-economic status. The educational implications of these results are discussed and the problem of the definition of shyness is addressed. The sample comprised 650 adolescents in the age range 11-18 years, drawn at random from two secondary schools, the number of boys being 300 and the number of girls 350. The results indicate that high levels of both situational and inherent shyness are related significantly to high levels of anxiety and neuroticism. Inherent shyness and situational shyness correlate only moderately with one another. Low levels of situational and inherent shyness are related positively and significantly to high levels of self-esteem and extraversion. Similar patterns of relationships occur for the other variables considered. The stability coefficients of correlations for each type of shyness were high after an interval of six months. Furthermore, shyness is related significantly to the socio-economic class of adolescents: a relatively higher percentage of shyness occurs among adolescents of lower socio-economic class.

Achievement↗
PubMed1992

Reproducibility of measurements of blood pressure in a tropical environment.

The reproducibility of measurements of the blood pressure of 65 adult male Gambians was investigated to assess the role that replication of measurements may have in epidemiological studies in a tropical environment. Observations were made at approximately seven week intervals over a period of 15 months and measurements were repeated three times on each occasion a subject was seen. The magnitude of the variation of an individual subject's BP between occasions, and between readings on the same occasion, was comparable with those which have been observed in studies in developed countries in temperate climates. The variation between occasions was greater than that between readings on the same occasion. There was a significant fall in systolic pressure between the first and third occasions, and a more gradual fall in diastolic pressure. The observations suggest that an individual subject's BP level would be better characterized by making a second reading on another occasion than by making three or more readings on the same occasion. These results have implications for the design of epidemiological studies and for the diagnosis of hypertension in the tropics.

Adult↗
PubMed1992

An investigation of some risk factors for severe leptospirosis on Barbados.

Between November 1979 and the end of December 1986 (7.17 years), 248 cases of leptospirosis were confirmed among hospital patients on Barbados (mean 35 per year; range 25-57). Considering the 235 who were greater than or equal to 15 years of age, the annual incidence of leptospirosis was 19.2/100,000 population (14.0 for all age groups). There were 173 males and 62 females, and for cases aged 15-34 leptospirosis was 9.6 times more common in men than women. Among men, incidence increased fairly steadily with age, and an even steadier increase was apparent in women up to age 64, with some decline in later years. The incidence of disease was much higher among agricultural than other workers and the non-employed. Highest case numbers were recorded in the parishes of St Michael (65 or 28%) and Christ Church (36 or 15%), though the incidence was lowest in these two parishes (13.1/100,000 and 17.4/100,000, respectively). The highest incidence rates were in St Andrew and St Joseph (50.2 and 36.1/100,000, respectively). The incidence in areas with rainfall greater than or equal to 1600 mm (32.6/100,000) was nearly twice that in areas with rainfall less than 1600 mm (17.3/100,000). There is a clear link between cases of severe disease and recent rainfall. Using 134 patients greater than or equal to 15 years of age with fever due to other illnesses as controls, a higher proportion of cases than controls came from rural areas. The risk of contracting leptospirosis was increased for all categories of manual workers relative to the group at lowest risk (non-manual indoor workers). Sugar-cane workers were five times more likely to contract leptospirosis than were non-manual indoor workers, while those whose families minded livestock were 2.5 times more likely, and those with rodents in their garden/yard were 1.8 times more likely to do so. Other risk factors examined did not show significant associations with the disease. Despite increasing mechanization and the use of more protective clothing, agricultural workers are still at high risk from leptospirosis. The annual range of cases is likely to stay much as it is in the foreseeable future.

Adolescent↗