Department of Medical Biochemistry
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Item Glucose-6-phosphate dehydrogenase deficiency genotypes and allele frequencies in the Kavango and Zambezi regions of northern Namibia(Transactions of the Royal Society of Tropical Medicine and Hygiene, 2019-04-09) Ababio, G; Haiyambo, D.H.; Ilunga, A.; Nangombe, R.; Hatuikulipi, T.; Aleksenko, L.; Misihairabgwi, J.; Uusiku, P.; Pernica, J.M.; Greco, B.; Quaye, I.K.Background: Namibia has made significant gains in the fight against malaria, with a target of elimination by 2023. We examined the genotype and allele frequencies of glucose-6-phosphate dehydrogenase (G6PD) deficiency to inform decisions on primaquine use, as we recently detected clusters of Plasmodium ovale curtisi in Kavango. Methods: A multistaged cross-sectional sampling method was used to enrol 212 children 2–9 y of age from schools and clinics in the Okavango and Zambezi regions of northern Namibia. Genotypes for the 202 G→A and 376 A→G mutations were assigned by polymerase chain reaction restriction fragment length polymorphism. Results: Of the 212 subjects enrolled, genotypes were available for 210, made up of 61 males and 149 females. G6PD-deficient males (hemizygotes) and females (homozygotes) constituted 3.27% (2/61) and 0.0% (0/149), respectively. Female heterozygotes (AA− and BA−) constituted 10.07% (15/149), while G6PD wild-type males (with A or B haplotype) and females (with AA, BB or AB haplotypes) consisted of 96.72% (59/61) and 89.93% (134/149), respectively. The A−, A and B allele frequencies were 0.0474, 0.3036 and 0.6490, respectively. Hardy–Weinberg equilibrium tests for female genotype frequencies did not show deviation (p=0.29). Conclusions: The frequency of G6PD deficiency alleles in males in the Kavango and Zambezi regions of northern Namibia constitute 3.27%, a first report to inform policy on primaquine role out.Item A model for height and sex prediction from percutaneous lengths of forearm bones(Australian Journal of Forensic Sciences, 2019) Okai, I.; Pianim, A.A.; Arko-Boham, B.; Acheampong, E.Estimating the probable height, sex and age of unknown human remains is not uncommon to forensic experts. Applying mathematical formula derived from metric data of a population is accepted as an alternative when anatomical methods are not feasible during this process of identification. Although each population has to generate their own formulae because of differences in the genetic, environmental and racial attributes of populations, little is known of Ghanaians. Thus, we attempted to derive equations for height and sex prediction, by measuring the ulna and radial lengths of 300 Ghanaian subjects, composed of 160 males and 140 females, with a spreading calliper and a tape measure, and their heights with a stadiometer. Regressions and discriminant function analysis were applied to the variables in SPSS to generate formulae for height and sex prediction respectively. The mean height, ulna length and radial length for sampled individuals were 167.4, 28.6 and 25.9 cm respectively. Height exhibited a strong and significant positive correlation with ulna length (r = 0.720, p < 0.0001) and radial length (r = 0.664, p < 0.0001). However, for our data, ulna length is a better predictor of height and sex than radial length. Overall accuracy of sex determination based on radial or ulna length alone was 75.3% and 82.3% respectively. © 2018, © 2018 Australian Academy of Forensic Sciences.Item Antioxidant activity of solvent fractions of taraxacum officinale (dandelion) leaves(Journal of Herbs, Spices and Medicinal Plants, 2014-05) Tettey, C.O.; Ocloo, A.; Nagajyothi, P.C.; Lee, K.D.Methanolic crude extract of dandelion (Taraxacum officinale) leaves was fractionated in solvents and antioxidant activity evaluated. The ethyl acetate and butanol fractions showed high antioxidant activities in all the assays. Methylene chloride and water fractions demonstrated moderate activity, whereas the hexane fraction had relatively lower activity. Copyright © Taylor & Francis Group, LLC.Item Identification of fluorinases from streptomyces sp MA37, norcardia brasiliensis, and actinoplanes sp N902-109 by genome mining(ChemBioChem, 2014) Deng, H.; Ma, L.; Bandaranayaka, N.; Qin, Z.; Mann, G.; Kyeremeh, K.; Yu, Y.; Shepherd, T.; Naismith, J.H.; O'Hagan, D.The fluorinase is an enzyme that catalyses the combination of S-adenosyl-L-methionine (SAM) and a fluoride ion to generate 5′-fluorodeoxy adenosine (FDA) and L-methionine through a nucleophilic substitution reaction with a fluoride ion as the nucleophile. It is the only native fluorination enzyme that has been characterised. The fluorinase was isolated in 2002 from Streptomyces cattleya, and, to date, this has been the only source of the fluorinase enzyme. Herein, we report three new fluorinase isolates that have been identified by genome mining. The novel fluorinases from Streptomyces sp. MA37, Nocardia brasiliensis, and an Actinoplanes sp. have high homology (80-87 % identity) to the original S. cattleya enzyme. They all possess a characteristic 21-residue loop. The three newly identified genes were overexpressed in E. coli and shown to be fluorination enzymes. An X-ray crystallographic study of the Streptomyces sp. MA37 enzyme demonstrated that it is almost identical in structure to the original fluorinase. Culturing of the Streptomyces sp. MA37 strain demonstrated that it not only also elaborates the fluorometabolites, fluoroacetate and 4-fluorothreonine, similar to S. cattleya, but this strain also produces a range of unidentified fluorometabolites. These are the first new fluorinases to be reported since the first isolate, over a decade ago, and their identification extends the range of fluorination genes available for fluorination biotechnology. Get on the fluor! The fluorinase enzyme from Streptomyces cattleya was identified in 2002 as the only fluorination enzyme known in biochemistry. Three additional fluorinases expressed through bacterial genome mining are now reported. These new fluorinases extend the range of genes available for developing fluorination biotechnology. Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.Item HIV-1 CRF 02 AG polymerase genes in southern Ghana are mosaics of different 02 AG strains and the protease gene cannot infer subtypes.(2009) Sagoe, K.W.; Dwidar, M.; Adiku, T.K.; Arens, M.Q.Background. Little is known about the detailed phylogeny relationships of CRF 02-AG HIV-1 polymerase genes in Ghana. The use of the protease gene of HIV-1 for subtyping has shown conflicting results. Methods. The partial polymerase gene sequences of 25 HIV-1 strains obtained with Viroseq reagents were aligned with reference subtypes and alignments trimmed to a 300 bp protease, 661 bp and 1005 reverse transcriptase sequence alignments. Phylogenetic relationships of these alignments were determined with the Neighbour-Joining method using 1000 replicates and recombination patterns determined for the sequences with RIP 3.0 in the HIV sequence database. Results. Unlike the other alignments, the protease gene had nodes with bootstrap values < 100% for repeat control sequences. Majority of the CRF 02-AG sequences from Ghana were made up of fragments of several strains of CRF 02-AG/AG strains. The protease gene alone is not suitable for phylogenetic analysis. Conclusion. The polymerase genes of HIV-1 strains from Ghana are made up of recombinants of several CRF 02-AG strains from Ghana, Senegal and Cameroon, but the clinical implications are unknown. Using the HIV-1 protease gene for subtyping will not infer subtypes correctly.Item Understanding the effect of side groups in ionic liquids on carbon-capture properties: a combined experimental and theoretical effort.(2013-03-07) Yan, F.; Lartey, M.; Damodaran, K.; Albenze, E.; Thompson, R.L.; Kim, J.; Haranczyk, M.; Nulwala, H.B.; Luebke, D.R.; Smit, B.Ionic liquids are an emerging class of materials with applications in a variety of fields. Steady progress has been made in the creation of ionic liquids tailored to specific applications. However, the understanding of the underlying structure-property relationships has been slower to develop. As a step in the effort to alleviate this deficiency, the influence of side groups on ionic liquid properties has been studied through an integrated approach utilizing synthesis, experimental determination of properties, and simulation techniques. To achieve this goal, a classical force field in the framework of OPLS/Amber force fields has been developed to predict ionic liquid properties accurately. Cu(I)-catalyzed click chemistry was employed to synthesize triazolium-based ionic liquids with diverse side groups. Values of densities were predicted within 3% of experimental values, whereas self-diffusion coefficients were underestimated by about an order of magnitude though the trends were in excellent agreement, the activation energy calculated in simulation correlates well with experimental values. The predicted Henry coefficient for CO(2) solubility reproduced the experimentally observed trends. This study highlights the importance of integrating experimental and computational approaches in property prediction and materials development, which is not only useful in the development of ionic liquids for CO(2) capture but has application in many technological fields.Item Low HDL-cholesterol with normal triglyceride levels is the most common lipid pattern in West Africans and African Americans with metabolic syndrome: Implications for cardiovascular disease prevention(CVD Prevention and Control, 2010-09) Sumner, A.E.; Zhou, J.; Doumatey, A.; Imoisili, O.E.; Amoah, A.; Acheampong, J.; Oli, J.; Johnson, T.; Adebamowo, C.; Rotimi, C.N.Background: Although designed to predict cardiovascular disease and type 2 diabetes mellitus, the Metabolic Syndrome (MetSyn) under-predicts these conditions in African Americans (AA). Failure of MetSyn in AA is often attributed to their relative absence of hypertriglyceridemia. It is unknown if the African experience with MetSyn will be similar or different to that in AA. Focusing on the lipid profile, our goal was to determine in West Africans (WA) and AA the pattern of variables that leads to the diagnosis of the MetSyn. Methods: Cross-sectional analysis of 1296 subjects (364 WA, 44% male, 932 AA, 46% male). WA were from urban centers in Nigeria and Ghana and enrolled in the Africa America Diabetes Mellitus Study. AA lived in Washington, DC and participated in the Howard University Family Study. Results: The prevalence of MetSyn was different in WA women and men: 42% vs.19%, P < 0.001, and in AA women and men: 25% vs.17%, P < 0.01. The three variables that most often led to the diagnosis of MetSyn in WA and AA were: low HDL-C, central obesity and hypertension. Less than 40% of AA and less than 25% of WA with the MetSyn had hypertriglyceridemia. Conclusions: Elevated triglyceride levels were uncommon in both WA and AA with MetSyn. As the relative absence of hypertriglyceridemia is associated with a lack of efficacy of MetSyn in AA, caution is warranted in diagnosing MetSyn in WA, the ancestral population of AA. Prospective studies are necessary to determine if an ethnic-specific reformulation of the MetSyn scoring system for lipids might optimize risk identification in black populations.Item In search of susceptibility genes for type 2 diabetes in west africa: The design and results of the first phase of the AADM study(Annals of Epidemiology, 2001) Rotimi, C.N.; Dunston, G.M.; Berg, K.; Akinsete, O.; Amoah, A.; Owusu, S.; Acheampong, J.; Boateng, K.; Oli, J.; Okafor, G.; Onyenekwe, B.; Osotimehin, B.; Abbiyesuku, F.; Johnson, T.; Fasanmade, O.; Furbert-Harris, P.; Kittles, R.; Vekich, M.; Adegoke, O.; Bonney, G.; Collins, F.PURPOSE: The purpose of this study is to map type 2 diabetes susceptibility genes in West African ancestral populations of African-Americans, through an international collaboration between West African and US investigators. DESIGN AND METHODS: Affected sib-pairs (ASP) along with unaffected spouse controls are being enrolled and examined in West Africa, with two sites established in Ghana (Accra and Kumasi) and three in Nigeria (Enugu, Ibadan, and Lagos). Eligible participants are invited to study clinics to obtain detailed epidemiologic, family, and medical history information. Blood samples are drawn from each participant to measure glucose, insulin, C-peptide, total cholesterol, LDL, HDL, triglycerides, albumin, creatinine, urea, uric acid, total calcium and to detect autoantibodies to glutamic acid decarboxylase (GAD). DNA is isolated from frozen white blood cells obtained from 20 ml of EDTA whole blood samples. RESULTS: With full informed consent, 162 individuals from 78 families have been enrolled and examined since the Africa America Diabetes Mellitus (AADM) study began in June of 1997. Logistics of field examinations and specimen shipping have been successfully established. At the end of the third year of field activity (September 2000) the AADM study will have enrolled and performed comprehensive examination on 400 ASP with type 2 diabetes, for a minimum of 800 cases and 200 controls from Ghana and Nigeria. At the current participation rate, the goal of 400 sib-pairs and 200 controls will be met before the scheduled closing date. CONCLUSIONS: The AADM study will create a comprehensive epidemiologic and genetic resource that will facilitate a powerful genome-wide search for West African susceptibility genes to type 2 diabetes.Item Prevalence and determinants of diabetic retinopathy and cataracts in west african type 2 diabetes patients(Ethnicity and Disease, 2003-06) Rotimi, C.; Daniel, H.; Zhou, J.; Obisesan, A.; Chen, G.; Chen, Y.; Amoah, A.; Opoku, V.; Acheampong, J.; Agyenim-Boateng, K.; Eghan Jr., B.A.; Oli, J.; Okafor, G.; Ofeogbu, E.; Osotimehin, B.; Abbiyesuku, F.; Johnson, T.; Fasanmade, O.; Doumatey, A.; Aje, T.; Collins, F.; Dunston, G.Objective: To quantify the prevalence of, and risk factors for, diabetic retinopathy and cataracts in patients with type 2 diabetes, and their spouse controls, enrolled from 5 centers in 2 West African countries (Ghana and Nigeria). Method: The analysis cohort was made up of 840 subjects with type 2 diabetes, and their 191 unaffected spouse controls, who were enrolled and examined in Lagos, Enugu, and Ibadan, in Nigeria, and in Accra and Kumasi, in Ghana. A diagnosis of diabetic retinopathy was made only where a participant had a minimum of one microaneurysm in any field, as well as exhibiting hemorrhages (dot, blot, or flame shaped), and maculopathy (with or without clinically significant edema). Results: Average duration of diabetes was 7.0 years, and mean age at diagnosis was 46.5 years. Prevalence of diabetic retinopathy was 17.9%. Cataracts were present in 44.9% of the patients with type 2 diabetes, and in 18.3% of spouse controls. The risk of developing retinopathy increased more than 3-fold for patients at the highest fasting plasma glucose (FPG) level (OR=3.4; 95% CI, 1.8-6.3), compared to patients at the lowest FPG level. The odds ratios for persons with diabetes for 10 years or more, compared to persons with diabetes for less than 5 years, was 7.3 (95% CI, 4.3-12.3) for retinopathy, and 2.6 (95% CI, 1.5-4.5) for cataracts. Conclusions: Cataracts were a more important cause of vision impairment than was diabetic retinopathy in this cohort. The prevalence of cataracts in patients with diabetes was more than twice that of their spouse controls, indicating that type 2 diabetes is an important risk factor for cataract formation. Individuals who developed type 2 diabetes at an earlier age were more likely to develop both diabetic retinopathy and cataracts. A strong positive association was observed between FPG level, duration of diabetes, and risk of retinopathy and cataracts. The low prevalence of retinopathy and cataracts observed within the first 5 years of diagnosis of diabetes in this cohort, suggests that intensive blood glucose control may reduce the risk of the development and progression of retinopathy and cataracts. In this regard, early eye examination, preferably at first presentation of elevated blood glucose, is highly recommended.Item The drakensberg declaration on the control of rheumatic fever and rheumatic heart disease in africa(South African Medical Journal, 2006-03) Mayosi, B.; Robertson, K.; Volmink, J.; Adebo, W.; Akinyore, K.; Amoah, A.; Bannerman, C.; Biesman-Simons, S.; Carpetis, J.; Cilliers, A.; Commerford, P.; Croasdale, A.; Damasceno, A.; Dean, J.; Dean, M.; De-Souza, R.; Filipe, A.; Hugo-Hamman, C.; Jurgens-Clur, S.A.; Kombila-Koumba, P.; Kotzenberg, C.; Lawrenson, J.; Manga, P.; Matenga, J.; Mathivha, T.; Mntla, P.; Mocumbi, A.; Mokone, T.; Ogola, E.; Omokhodion, S.; Palweni, C.; Pearce, A.; Salo, A.; Thomas, B.; Walker, K.; Wiysonge, C.; Zaher, S.