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1.
Ansong D Asante KP Vekemans J Owusu SK Owusu R Brobby NA Dosoo D Osei-Akoto A Osei-Kwakye K Asafo-Adjei E Boahen KO Sylverken J Adjei G Sambian D Apanga S Kayan K Janssens MH Lievens MJ Olivier AC Jongert E Dubois P Savarese BM Cohen J Antwi S Greenwood BM Evans JA Agbenyega T Moris PJ Owusu-Agyei S 《PloS one》2011,6(4):e18891
Background
The Plasmodium falciparum pre-erythrocytic stage candidate vaccine RTS,S is being developed for protection of young children against malaria in sub-Saharan Africa. RTS,S formulated with the liposome based adjuvant AS01E or the oil-in-water based adjuvant AS02D induces P. falciparum circumsporozoite (CSP) antigen-specific antibody and T cell responses which have been associated with protection in the experimental malaria challenge model in adults.Methods
This study was designed to evaluate the safety and immunogenicity induced over a 19 month period by three vaccination schedules (0,1-, 0,1,2- and 0,1,7-month) of RTS,S/AS01E and RTS,S/AS02D in children aged 5–17 months in two research centers in Ghana. Control Rabies vaccine using the 0,1,2-month schedule was used in one of two study sites.Results
Whole blood antigen stimulation followed by intra-cellular cytokine staining showed RTS,S/AS01E induced CSP specific CD4 T cells producing IL-2, TNF-α, and IFN-γ. Higher T cell responses were induced by a 0,1,7-month immunization schedule as compared with a 0,1- or 0,1,2-month schedule. RTS,S/AS01E induced higher CD4 T cell responses as compared to RTS,S/AS02D when given on a 0,1,7-month schedule.Conclusions
These findings support further Phase III evaluation of RTS,S/AS01E. The role of immune effectors and immunization schedules on vaccine protection are currently under evaluation.Trial Registration
ClinicalTrials.gov NCT00360230相似文献2.
3.
Dennis Adu-Gyasi Kwaku Poku Asante Sam Newton David Dosoo Sabastina Amoako George Adjei Nicholas Amoako Love Ankrah Samuel Kofi Tchum Emmanuel Mahama Veronica Agyemang Kingsley Kayan Seth Owusu-Agyei 《PloS one》2015,10(4)
Background
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most widespread enzyme defect that can result in red cell breakdown under oxidative stress when exposed to certain medicines including antimalarials. We evaluated the diagnostic accuracy of CareStart G6PD deficiency Rapid Diagnostic Test (RDT) as a point-of-care tool for screening G6PD deficiency.Methods
A cross-sectional study was conducted among 206 randomly selected and consented participants from a group with known G6PD deficiency status between February 2013 and June 2013. A maximum of 1.6ml of capillary blood samples were used for G6PD deficiency screening using CareStart G6PD RDT and Trinity qualitative with Trinity quantitative methods as the “gold standard”. Samples were also screened for the presence of malaria parasites. Data entry and analysis were done using Microsoft Access 2010 and Stata Software version 12. Kintampo Health Research Centre Institutional Ethics Committee granted ethical approval.Results
The sensitivity (SE) and specificity (SP) of CareStart G6PD deficiency RDT was 100% and 72.1% compared to Trinity quantitative method respectively and was 98.9% and 96.2% compared to Trinity qualitative method. Malaria infection status had no significant (P=0.199) change on the performance of the G6PD RDT test kit compared to the “gold standard”.Conclusions
The outcome of this study suggests that the diagnostic performance of the CareStart G6PD deficiency RDT kit was high and it is acceptable at determining the G6PD deficiency status in a high malaria endemic area in Ghana. The RDT kit presents as an attractive tool for point-of-care G6PD deficiency for rapid testing in areas with high temperatures and less expertise. The CareStart G6PD deficiency RDT kit could be used to screen malaria patients before administration of the fixed dose primaquine with artemisinin-based combination therapy. 相似文献4.
Spontaneous homologous recombination is induced by collapsed replication forks that are caused by endogenous DNA single-strand breaks 总被引:1,自引:0,他引:1 下载免费PDF全文
Saleh-Gohari N Bryant HE Schultz N Parker KM Cassel TN Helleday T 《Molecular and cellular biology》2005,25(16):7158-7169
Homologous recombination is vital to repair fatal DNA damage during DNA replication. However, very little is known about the substrates or repair pathways for homologous recombination in mammalian cells. Here, we have compared the recombination products produced spontaneously with those produced following induction of DNA double-strand breaks (DSBs) with the I-SceI restriction endonuclease or after stalling or collapsing replication forks following treatment with thymidine or camptothecin, respectively. We show that each lesion produces different spectra of recombinants, suggesting differential use of homologous recombination pathways in repair of these lesions. The spontaneous spectrum most resembled the spectra produced at collapsed replication forks formed when a replication fork runs into camptothecin-stabilized DNA single-strand breaks (SSBs) within the topoisomerase I cleavage complex. We found that camptothecin-induced DSBs and the resulting recombination repair require replication, showing that a collapsed fork is the substrate for camptothecin-induced recombination. An SSB repair-defective cell line, EM9 with an XRCC1 mutation, has an increased number of spontaneous gammaH2Ax and RAD51 foci, suggesting that endogenous SSBs collapse replication forks, triggering recombination repair. Furthermore, we show that gammaH2Ax, DSBs, and RAD51 foci are synergistically induced in EM9 cells with camptothecin, suggesting that lack of SSB repair in EM9 causes more collapsed forks and more recombination repair. Furthermore, our results suggest that two-ended DSBs are rare substrates for spontaneous homologous recombination in a mammalian fibroblast cell line. Interestingly, all spectra showed evidence of multiple homologous recombination events in 8 to 16% of clones. However, there was no increase in homologous recombination genomewide in these clones nor were the events dependent on each other; rather, we suggest that a first homologous recombination event frequently triggers a second event at the same locus in mammalian cells. 相似文献
5.
Nermin Biricik Cezmi Kayan Zhaofu Fei Paul J. Dyson ?smail Özdemir 《Inorganica chimica acta》2010,363(5):1039-1047
Four new bis(phosphino)amine ligands (Ph2P)2N-C6H3-R, where R = 3,5-OMe (1), 2,5-OMe (2), 2,4-OMe (3) or 3,4-OMe (4), were prepared via aminolysis of the corresponding dimethoxyanilines with 2 equiv. of diphenylphosphine chloride in the presence of triethyl amine. Oxidation of these ligands with aqueous H2O2, elemental S8 or Se powder afforded the corresponding chalcogen oxides 1a-4a, sulfides 1b-4b and selenides 1c-4c in good yields. Reaction of 1-4 with [MCl2(cod)] (M = Pt, Pd; cod = cycloocta-1,5-diene) in equimolar ratios afforded cis-[MCl2{(Ph2P)2N-C6H3-R}] (M = Pt; R = 3,5-OMe 1d, R = 2,5-OMe 2d, R = 2,4-OMe 3d, and R = 3,4-OMe 4d. M = Pd; R = 3,5-OMe 1e, R = 2,5-OMe 2e, R = 2,4-OMe 3e, and R = 3,4-OMe 4e). Similarly, reaction of [Cu(CH3CN)4]PF6 with the 1-4 in 1:2 ratio gave [Cu{(Ph2P)2N-C6H3-R}2]PF6 (R = 3,5-OMe 1f, 2,5-OMe 2f, 2,4-OMe 3f and 3,4-OMe 4f). All new compounds were fully characterized by spectroscopy and elemental analysis and the molecular structures of seven representative compounds were determined by single-crystal X-ray crystallography. In addition, the palladium complexes were investigated as pre-catalysts in C-C coupling reactions. 相似文献
6.
Validation of microsatellite multiplexes for parentage analysis and species discrimination in two hybridizing species of coral reef fish (Plectropomus spp., Serranidae) 下载免费PDF全文
Hugo B. Harrison Kevin A. Feldheim Geoffrey P. Jones Kayan Ma Hicham Mansour Sadhasivam Perumal David H. Williamson Michael L. Berumen 《Ecology and evolution》2014,4(11):2046-2057
Microsatellites are often considered ideal markers to investigate ecological processes in animal populations. They are regularly used as genetic barcodes to identify species, individuals, and infer familial relationships. However, such applications are highly sensitive the number and diversity of microsatellite markers, which are also prone to error. Here, we propose a novel framework to assess the suitability of microsatellite datasets for parentage analysis and species discrimination in two closely related species of coral reef fish, Plectropomus leopardus and P. maculatus (Serranidae). Coral trout are important fisheries species throughout the Indo‐Pacific region and have been shown to hybridize in parts of the Great Barrier Reef, Australia. We first describe the development of 25 microsatellite loci and their integration to three multiplex PCRs that co‐amplify in both species. Using simulations, we demonstrate that the complete suite of markers provides appropriate power to discriminate between species, detect hybrid individuals, and resolve parent–offspring relationships in natural populations, with over 99.6% accuracy in parent–offspring assignments. The markers were also tested on seven additional species within the Plectropomus genus with polymorphism in 28–96% of loci. The multiplex PCRs developed here provide a reliable and cost‐effective strategy to investigate evolutionary and ecological dynamics and will be broadly applicable in studies of wild populations and aquaculture brood stocks for these closely related fish species. 相似文献
7.
Haematological and biochemical reference values for healthy adults in the middle belt of Ghana 总被引:1,自引:0,他引:1
Dosoo DK Kayan K Adu-Gyasi D Kwara E Ocran J Osei-Kwakye K Mahama E Amenga-Etego S Bilson P Asante KP Koram KA Owusu-Agyei S 《PloS one》2012,7(4):e36308
Background
Reference values are very important in clinical management of patients, screening participants for enrolment into clinical trials and for monitoring the onset of adverse events during these trials. The aim of this was to establish gender-specific haematological and biochemical reference values for healthy adults in the central part of Ghana.Methods
A total of 691 adults between 18 and 59 years resident in the Kintampo North Municipality and South District in the central part of Ghana were randomly selected using the Kintampo Health and Demographic Surveillance System and enrolled in this cross-sectional survey. Out of these, 625 adults made up of 316 males and 309 females were assessed by a clinician to be healthy. Median values and nonparametric 95% reference values for 16 haematology and 22 biochemistry parameters were determined for this population based on the Clinical Laboratory and Standards Institute guidelines. Values established in this study were compared with the Caucasian values being used currently by our laboratory as reference values and also with data from other African and western countries.Results
Reference values established include: haemoglobin 113–164 g/L for males and 88–144 g/L for females; total white blood cell count 3.4–9.2×109/L; platelet count 88–352×109/L for males and 89–403×109/L for females; alanine aminotransferase 8–54 U/L for males and 6–51 U/L for females; creatinine 56–119 µmol/L for males and 53–106 µmol/L for females. Using the haematological reference values based on the package inserts would have screened out up to 53% of potential trial participants and up to 25% of the population using the biochemical parameters.Conclusion
We have established a panel of locally relevant reference parameters for commonly used haematological and biochemical tests. This is important as it will help in the interpretation of laboratory results both for clinical management of patients and safety monitoring during a trial. 相似文献8.
Mustafa Kayan Mustafa Naz?ro?lu ?shak Suat ?vey Mehmet Aykur Abdülhadi Cihangir U?uz Vedat Ali Yürekli 《The Journal of membrane biology》2012,245(12):833-840
Non-ionic contrast media (CM) can induce tissue kidney injury via activation of phagocytosis and oxidative stress, although the mechanisms of injury via neutrophils are not clear. We investigated the effects of CM on oxidative stress and Ca2+ concentrations in serum and neutrophils of humans. Ten migraine patients were used in the study. Serum and neutrophil samples from patients?? peripheral blood were obtained before (control) and 30?min after non-ionic (iopromide) CM injection. The neutrophils were incubated with non specific transient receptor potential 2 (TRPM2) channel blocker, 2-aminoethoxydiphenyl borate (2-APB), and voltage gated Ca2+ channel blockers, verapamil plus diltiazem. Serum and neutrophil lipid peroxidation, apoptosis and intracellular Ca2+ concentrations levels were higher in the CM group than in controls. The neutrophilic reduced glutathione (GSH) and glutathione peroxidase (GSH-Px) levels as well as serum vitamin E and ??-carotene concentrations were lower in the CM group than in controls. Neutrophil lipid peroxidation levels were lower in the CM+2-APB and CM+verapamil-diltiazem groups than in the CM group, although GSH, GSH-Px and intracellular Ca2+ values increased in the CM+2-APB and CM+verapamil-diltiazem groups. However, caspase-3, caspase-9, vitamin A and vitamin C values were unaltered by CM treatment. In conclusion, we observed that CM induced oxidative stress and Ca2+ influx by decreasing vitamin E, ??-carotene and Ca2+ release levels in human serum and neutrophils. However, we observed protective effects of Ca2+ channel blockers on Ca2+ influx in neutrophils. 相似文献
9.
X-ray radiation is detrimental to human cells and may lead to development of life-threatening diseases. Cigarette paper and
cigarette smoke contain toxic elements, whereas vitamins C and E (VCE) may have regulator effects on the elements. We investigated
effects of VCE administration on X-ray-induced element changes in blood of smoker and nonsmoker X-ray technicians. Twenty
technicians and 30 healthy age-matched control subjects were used in the study. Ten of the X-ray technicians and 15 of the
control were smokers. Blood serum samples were taken from the control. Oral vitamins C (500 mg) and E (150 mg) were supplemented
daily to the smoker and nonsmoker X-ray technicians for 5 weeks. Serum samples were taken from the X-ray technicians before
and after 5 weeks. Copper, zinc, selenium, aluminum, iron, magnesium, and calcium levels were investigated in control and
X-ray technicians, both smokers and nonsmokers. Copper, zinc, and selenium levels were lower in the total X-ray group and
smoker X-ray group than in control and nonsmoker X-ray group, although iron, magnesium, and calcium levels were higher in
X-ray group than in control. The copper, zinc, selenium, and aluminum levels were higher in the VCE treatment group than those
in X-ray group, although magnesium and calcium levels were decreased by the treatment. The serum zinc, copper, selenium, and
magnesium levels were lower in smoker control group when compared to nonsmoker control group. The serum zinc levels were lower
in smoker X-ray group than nonsmoker X-ray group, although iron level was higher in smoker X-ray group than in nonsmoker X-ray
group. VCE prevents the smoke and X-ray-induced selenium, zinc, magnesium, and copper decrease to strengthen the antioxidant
trace element levels in the serum of the technicians. 相似文献
10.