A continuum approach to blood flow.
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Biomedical subjects
Publications and source records attributed to S J Allen.
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Cellular immune responses to the Plasmodium falciparum circumsporozoite (CS) protein were measured by proliferation and interferon-gamma production in a cohort of children aged 3 to 8 years, living in The Gambia. Anti-CS antibody titres, malariometric indices and sickle cell status were also determined. Malaria morbidity in the ensuing malaria transmission season was monitored by weekly health questionnaire, axillary temperature measurements and examination of blood films. Exposure to malaria was inferred from entomological data collected during the transmission season. Immunological and parasitological measurements were repeated at the end of the rainy season. Immunological findings were compared between children who experienced clinical malaria or asymptomatic infection and children who had no evidence of infection. No association was found between cellular immune responses to the CS protein at the beginning of the transmission season and subsequent susceptibility to infection except among children with high titres of antibody to (NANP)40. Seropositive children who did not become infected had a higher mean proliferative response to the Th3R epitope than seropositive children who did become infected. High titres of anti-(NANP)40 antibodies alone were not protective. Responses to the Th2R epitope were significantly higher at the end of the rainy season than at the beginning in children who experienced an asymptomatic infection. Responses to variant sequences of the 2 epitopes were highly correlated at an individual level but there was no correlation between proliferative and interferon responses to a particular epitope.
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A seroepidemiological and clinical study was performed in an area of West Africa (The Gambia) where Plasmodium falciparum is endemic with seasonal transmission. Plasma samples were tested by intermediate gel immunoelectrophoresis for antibodies against 7 soluble P. falciparum antigens. There were marked differences in the age-related pattern of antibody response to the different antigens. Antibodies to 4 of the antigens were acquired slowly with a maximum prevalence reached after 25-35 years of age. Antibodies against the 3 remaining antigens, including the endotoxin-like antigen, Ag7, were acquired earlier with a plateau of maximum prevalence reached after 5-11 years, i.e. at the time when morbidity due to malaria decreased. Children who had not appeared to be infected with malaria during the preceding transmission season had lower levels of antibodies to soluble antigens than did children who had had a documented attack of clinical malaria or parasitaemia. There was no difference in antibody profiles to soluble antigens between children with sickle cell trait and children with normal haemoglobin.
We have measured cellular and humoral immune responses to short synthetic peptides representing epitopes of the malaria vaccine candidate antigen Pf155/RESA in a longitudinal, prospective study of clinical immunity to Plasmodium falciparum malaria in a cohort of 354 Gambian children aged 3-8 years. A significant association was observed between presence of antibodies to the 3' repeat region peptide (EENV)6 and resistance to clinical malaria. The prevalence of protective antipeptide antibodies varied significantly between different ethnic groups, suggesting that immune recognition of some Pf155/RESA epitopes may be genetically regulated. There was no obvious association between proliferative or interferon gamma responses to T cell epitopes of Pf155/RESA and resistance to malaria infection or disease. At an individual level, the presence of peptide-binding antibodies was associated with the induction of interleukin 4 messenger ribonucleic acid expression in T cells activated with the overlapping T cell epitope EENVEHDA(EENV)2. This suggests that measurement of interleukin 4 production by T cells may represent a functional assay for T helper activity.
Morbidity from Plasmodium falciparum malaria and humoral and in vitro cellular immune responses to defined malaria antigens were measured in rural Gambian children with haemoglobin phenotype AS (HbAS) and in those with a normal haemoglobin (HbAA). In a survey undertaken during the dry season, HbAS children had a higher parasite rate than HbAA children but a lower prevalence of parasitaemia at a level of 500/microliters or greater. Malariometric indices measured during a rainy season survey were similar in the 2 groups of children. During the rainy season, the incidence of infection with P. falciparum did not vary with haemoglobin phenotype. However, in children aged 6 years or less, a significantly smaller proportion of HbAS children who acquired infection developed clinical symptoms than did HbAA children. During both the dry season and rainy season surveys, humoral and in vitro cellular immune responses to defined antigens from the sporozoite and merozoite stages of P. falciparum were similar in the 2 groups of children. Thus, despite the differences in parasite indices and morbidity from malaria between the 2 groups of children, we found no evidence of an enhanced immune response to malaria infection amongst HbAS children compared with normal children.
Aflatoxin-albumin adduct levels were measured in serum samples obtained from a group of Gambian children. The relationships between exposure to aflatoxin and the prevalence of malaria, between exposure and humoral and cellular responses in vitro to defined malaria antigens and, amongst children with evidence of exposure to hepatitis B infection, between aflatoxin and carriage of the hepatitis B surface antigen (HBsAg), were assessed. Aflatoxin-albumin adduct was found in nearly all serum samples collected during a survey performed at the end of the dry season and levels of adduct were generally high (up to 720 pg aflatoxin-lysine equivalent/mg albumin). Higher levels of aflatoxin-albumin adduct were detected in Wollof children than in children of other ethnic groups and marked variation in mean adduct levels between villages was observed. Aflatoxin-albumin adduct levels were higher in children who were HbsAg positive and in children with Plasmodium falciparum parasitaemia than in controls. However, levels of adduct had no consistent effect on either malaria-specific antibody responses, lymphoproliferative responses in vitro, or morbidity from malaria during the subsequent rainy season. Much lower levels of aflatoxin-albumin adduct were detected in repeat samples obtained at the end of the rainy season. There was poor correlation between dry and rainy season levels of adduct in individual children. We have shown that Gambian children are exposed to high levels of aflatoxin. The seasonal variation of aflatoxin-albumin adduct and marked fluctuation of adduct with time in individual children need to be considered in the future planning of epidemiological studies using this marker of exposure.(ABSTRACT TRUNCATED AT 250 WORDS)
The protective effect of alpha thalassaemia (-alpha/alpha alpha) against morbidity from falciparum malaria was assessed in a prospective study of rural Gambian children. The gene frequency for single alpha-globin gene deletions was 0.12. Malariometric indices measured during cross-sectional surveys and morbidity from malaria determined by weekly surveillance were similar in children with alpha thalassaemia and in those with a normal alpha-globin genotype. However, the small number of children who carried both alpha thalassaemia and the sickle cell trait had fewer clinical episodes of malaria than children with the sickle cell trait alone. Specific antibody responses and cell-mediated immune responses in vitro to defined Plasmodium falciparum antigens were measured in children participating in the study. In general, there was no evidence of an increased prevalence or intensity of humoral or cell-mediated immune responses to the malaria antigens studied in children heterozygous for alpha thalassaemia compared with children with a normal alpha-globin genotype.
Human leucocyte antigen (HLA) class I and class II typing was performed on 177 children in a rural area of The Gambia who were followed for 2 years in a longitudinal study of malaria morbidity. A comparison was made between those who experienced an episode of clinical malaria in one or both years and those who showed no evidence of infection in either year. No convincing association was found between morbidity and class I phenotype. An overall association of morbidity with the distribution of class II haplotypes was seen, but association with individual DR-DQ haplotypes were not conclusive.
Gambian children who had received malaria chemoprophylaxis for a variable period of time during their first 5 years of life were followed to determine whether they experienced a rebound in mortality or in morbidity from malaria during the period after chemoprophylaxis was stopped. The risk of dying between the ages of 5 years, when chemoprophylaxis was stopped, and 10 years was no higher among children who had received chemoprophylaxis with Maloprim (pyrimethamine plus dapsone) for some period during their first 5 years of life than among children who had received placebo (21 vs. 24 deaths) and the beneficial effect of chemoprophylaxis on mortality observed during the first 5 years of life was sustained. The incidence of clinical attacks of malaria during the year after medication was stopped was significantly higher among children who had previously received Maloprim for several years than among children who had previously received placebo. However, at the end of this year, there was no significant difference in spleen rate, parasite rate or packed cell volume between the 2 groups of children. Thus, stopping chemoprophylaxis after a period of several years increased the risk of clinical malaria but did not result in a rebound in mortality in Gambian children. However, the number of deaths recorded was small, so a modest effect on mortality cannot be excluded.
Free-Electron Lasers (FELs) collectively operate from the terahertz through the ultraviolet range and via intracavity Compton backscattering into the X-ray and gamma-ray regimes. FELs are continuously tunable and can provide optical powers, pulse structures and polarizations that are not matched by conventional lasers. Representative research in the biological and biomedical sciences and condensed matter and material research are described to illustrate the breadth and impact of FEL applications. These include terahertz dynamics in materials far from equilibrium, infrared nonlinear vibrational spectroscopy to investigate dynamical processes in condensed-phase systems, infrared resonant-enhanced multiphoton ionization for gas-phase spectroscopy and spectrometry, infrared matrix-assisted laser-desorption-ionization and infrared matrix-assisted pulsed laser evaporation for analysis and processing of organic materials, human neurosurgery and ophthalmic surgery using a medical infrared FEL and ultraviolet photoemission electron microscopy for nanoscale characterization of materials and nanoscale phenomena. The ongoing development of ultraviolet and X-ray FELs are discussed in terms of future opportunities for applications research.
The focus of this study was to determine the optimum type of peat for application as a medium to capture dissolved metals from aqueous solution. Seventeen media were examined, including eleven Irish peat samples from various locations and stages in processing, a Northern Ireland lignite, peat and lignite chars, a commercial-grade bone char, and two commercial-grade granular activated carbons. Considerable variation in sorption capacity was found with a ratio of 20:1 between the best-performing (bone char) and the poorest-performing (peat char) samples. Among the 14 varieties of peat, the best-performing sample outperformed the commonly investigated sphagnum moss by a ratio of 4:1. A correlation has been established between cation exchange capacity, the presence of adsorbed calcium, and the uptake capacity of different peats. This correlation will be a valuable tool in choosing peat type for filter media for metals removal applications.
Seventeen patients with chemotherapy-resistant metastatic sarcoma were treated with whole body hyperthermia (WBH) combined simultaneously with 1-3-Bis(2-chloroethyl)-1-nitrosourea (BCNU). All of the patients had chemotherapy resistant metastases to major organ sites. Patients were heated to 41.8-42.0 degrees C for 2 h using an insulated blanket heating technique. Two patients (12%) experienced partial responses (PR). In addition, four objective tumour responses (OR) lasting more than 4 months were documented. One patient with previously rapidly growing chondrosarcoma pulmonary metastases experienced stable disease (SD) for 38 months from the onset of treatment. Median survival of seven patients with responding tumours (PR, OR and SD) compared with 10 patients with progressive disease was 15 versus 2 months, respectively. Cumulative thrombocytopenia was a therapy-limiting toxicity of the combined treatment, and occurred in six of seven patients. Acute toxicities attributable to WBH alone included transient thrombocytopenia in all patients, non-cardiogenic pulmonary oedema in two patients, and mild hypotension in five patients. Acute granulocytosis was observed in all patients. No treatment related deaths occurred. These data suggest that WBH combined with chemotherapy is associated with disease response in patients with chemotherapy-resistant, widely disseminated sarcoma metastases.
This work is an investigation on the use of manganese oxides-modified diatomite (MOMD) for the removal of color from textile wastewaters. The modification of the diatomite was carried out by treatment with manganese oxides; delta-bimessite type resulted. The surface area, pH(ZPC), Fourier transform infrared (FTIR), and scanning electron microscopy of MOMD were studied. The influence of concentration, pH, particle size, and temperature on the adsorption capacities of methylene blue (MB) and hydrolyzed reactive black (RB) and reactive yellow (RY) was investigated. Key thermodynamic parameters such as deltaH degrees, deltaS degrees, and deltaG degrees were also determined. The deltaH degrees of MB and hydrolyzed RB and RY was +94.64, -143.1, and -38.78 kJ/mol, respectively, whereas the deltaG degrees values of -17.68, -27.93, and -23.26 kJ/mol were obtained, indicating a spontaneous process with low activation-energy requirements. The findings further indicated that coulomb interaction, molecular size, and orientation of the dye and its surface charge played an important role in the adsorption and attachment of the dyes to the bimessite layers of MOMD.