Browsing by Author "Byarugaba, Wilson"
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Item B-cell non-Hodgkin lymphomas in Uganda: an immunohistochemical appraisal on tissue microarray(Human pathology, 2008) Tumwine, Lynnette K.; Campidelli, Cristina; Righi, Simona; Neda, Sophia; Byarugaba, Wilson; Pileri, Stefano A.The most common non-Hodgkin lymphomas in Uganda are neoplasms of B-cell derivation. The field of B-cell lymphoma immunophenotype has rapidly progressed because of the increasing availability of markers applicable to routine sections. Although the latter have allowed the identification of distinctive lymphoma entities in the developed countries, such approach has not yet been used in Uganda. One hundred twenty-nine formalin-fixed, paraffin-embedded tissue samples from the Department of Pathology of Makerere University were used for tissue micro-array (TMA) construction. Four-micrometer-thick sections were cut from TMAs and stained with hematoxylin and eosin and Giemsa. Theywere also used for immunohistochemistry and in situ hybridization.According to morphology and immunohistochemistry, lymphoid neoplasms were classified as Burkitt's lymphoma (BL) (95 cases), diffuse large B-cell lymphoma (19 cases), mantle cell lymphoma (4 cases), and B-cell lymphoblastic lymphoma (1 case). In BL, a homogeneous phenotype (CD10+, Bcl-6+, Bcl-2- , MUM1/IRF4-, and Ki-67 ~100%) and a stable Epstein-Barr virus integration were found. A distinctive and unusual feature was the frequent plasma cellular differentiation, along with the positivity for CD30 and CD138 (recorded in 35 and 43 cases, respectively). According to our findings, most non-Hodgkin B-cell tumors in Uganda are endemic BLs followed by diffuse large B-cell lymphomas. The rest consist of rare but clinically important entities such as mantle cell lymphoma and B-cell lymphoblastic lymphoma. The availability of TMAs and immunohistochemistry has enabled us to precisely categorize tumors that have so far been diagnosed in Uganda as “high-grade/aggressive” lymphomas on the basis of cell morphology alone. © 2008 Elsevier Inc. All rights reserved.Item EBV & HHV8 and HIV in B cell non Hodgkin lymphoma in Kampala, Uganda(Uganda Infectious Agents and Cancer, 2010) Tumwine, Lynnette K.; Orem, Jackson; Kerchan, Patrick; Byarugaba, Wilson; Pileri, Stefano A.B cell non Hodgkin lymphomas account for the majority of lymphomas in Uganda. The commonest is endemic Burkitt lymphoma, followed by diffuse large-B-cell lymphoma (DLBCL). There has been an increase in incidence of malignant lymphoma since the onset of the HIV/AIDS pandemic. However, the possible linkages of HHV8 and EBV to the condition of impaired immunity present in AIDS are still not yet very clearly understood.Item Emphasizing the vitality of genomics related research in the area of infectious diseases(Scientific Research and Essays, 2007) Wayengera, Misaki; Byarugaba, WilsonSequencing of the human and other species genomes has generated a downstream of sciences that have taken advantage of this knowledge to generate vital links between diseases and genetic variants. Sub-Saharan Africa and many developing countries form the major epicenters for Infectious diseases. Here, the role that genomics may hold in the area of infectious diseases research is emphasized in five blocks: phenotype evaluation studies, evolutionary trends’ studies across microbial and host genomes, idiopathic association or host susceptibility studies to disease, therapeutics or vaccine research insights, as well as the development of novel molecular diagnostics.Item Harnessing Pharmacogenomics to Tackle Resistance to the “Nucleoside Reverse Trancripatse Inhibitor” Backbone of Highly Active Antiretroviral Therapy in Resource Limited Settings(The open AIDS journal, 2008) Wayengera, Misaki; Kajumbula, Henry; Byarugaba, WilsonThe highest burden of the human immunodeficiency virus (HIV) epidemic is concentrated in the sub-Saharan region. Over 70% of all global HIV infections have been found to occur here [1]. Despite the earlier policy and patent controversies surrounding the use of highly active antiretroviral therapy (HAART) within this setting, HAART has widely gained application here [2]. This access to HAART can be mainly attributed to several advocacy and funding avenues [2-4]. Specifically, the World Bank and its global partners, in particular, with commitment by the G8, have ensured that several countries within this setting can meet the WHO 3’by 5” target of treating 3 million by 2005 [3,4].Item Hypoglycemic and Toxic Effect of Morus mesozygia Leaf Extract on the Liver and Kidneys of Alloxan-Induced Hyperglycemic Wistar Rats(Hindawi, 2019) Tirwomwe, Michael; Echoru, Isaac; Maseruka, Richard; Kimanje, Kyobe Ronald; Byarugaba, WilsonDiabetes mellitus (DM) is one of the leading causes of mortality and morbidity in developed and developing countries. DM is characterized by increased levels of glucose that eventually progress to frequent urination, increased thirst, and increased hunger [1]. According to global estimates of diabetes, in 2013, 382 million people had diabetes; this number is however expected to rise to 592 million by 2035. Majority of the people with diabetes live in low- and middle-income countries and these will experience the greatest increase in cases of diabetes over the next 22 years [2]. In Africa alone, about 12.1 million people lived with diabetes mellitus by 2010 [3, 4], and according to research, there will be an expected increment in the prevalence of DM in Asia and Africa by 2030. )is is because of increased urbanization and lifestyle changes that have changed the indigenous diet to a modern diet [5].Item Identification of restriction endonuclease with potential ability to cleave the HSV-2 genome: inherent potential for biosynthetic versus live recombinant microbicides(Theoretical Biology and Medical Modeling, 2008) Wayengera, Misaki; Kajumbula, Henry; Byarugaba, WilsonHerpes Simplex virus types 1 and 2 are enveloped viruses with a linear dsDNA genome of ~120–200 kb. Genital infection with HSV-2 has been denoted as a major risk factor for acquisition and transmission of HIV-1. Developing biomedical strategies for HSV-2 prevention is thus a central strategy in reducing global HIV-1 prevalence. This paper details the protocol for the isolation of restriction endonucleases (REases) with potent activity against the HSV-2 genome and models two biomedical interventions for preventing HSV-2.Item Immunohistochemical and other prognostic factors in B cell non Hodgkin lymphoma patients, Kampala, Uganda(BMC Clinical Pathology, 2009) Tumwine, Lynnette K.; Agostinelli, Claudio; Campidelli, Cristina; Othieno, Emmanuel; Wabinga, Henry; Righi, Simona; Falini, Brunangelo; Piccaluga, Pier Paolo; Byarugaba, WilsonNon Hodgkin lymphomas are the most common lymphomas in Uganda. Recent studies from developed countries have shown differences in survival for the different immunophenotypes. Such studies are lacking in Africa where diagnosis is largely dependent on morphology alone. We report immunohistochemical and other prognostic factors in B cell non Hodgkin lymphoma patients in Kampala, Uganda. Methods: Non Hodgkin lymphoma tissue blocks from the archives of the Department of Pathology, Makerere University College of Health Sciences, Kampala, Uganda, from 1991-2000, were sub typed using haematoxylin and eosin, Giemsa as well as immunohistochemistry. Using tissue micro array, 119 biopsies were subjected to: CD3, CD5, CD10, CD20, CD23, CD30, CD38, CD79a, CD138, Bcl-6, Bcl-2, IRTA-1, MUM1/IRF4, Bcl-1/cyclin D1, TdT, ALKc, and Ki-67/Mib1. Case notes were retrieved for: disease stage, chemotherapy courses received and retrospective follow up was done for survival.Item In silico evidence for the species-specific conservation of mosquito retroposons: implications as a molecular biomarker(Theoretical Biology and Medical Modelling, 2009) Byarugaba, Wilson; Kajumbula, Henry; Wayengera, MisakiMosquitoes are the transmissive vectors for several infectious pathogens that affect man. However, the control of mosquitoes through insecticide and pesticide spraying has proved difficult in the past. We hypothesized that, by virtue of their reported vertical inheritance among mosquitoes, group II introns – a class of small coding ribonucleic acids (scRNAs) – may form a potential species-specific biomarker. Structurally, introns are a six-moiety complex. Depending on the function of the protein encoded within the IV moiety, the highly mobile class of group II introns or retroposons is sub-divided into two: Restriction Endonuclease (REase)-like and Apurinic aPyramydinic Endonuclease (APE)-like. REase-like retroposons are thought to be the ancestors of APE retroposons. Our aim in this study was to find evidence for the highly species-specific conservation of the APE subclass of mosquito retroposons.Item Monitoring the severity of iodine deficiency disorders in Uganda(African Health Sciences, 2002) Bimenya, Gabriel S.; Okui, Olico; Kaviri, Dentos; Mbona, Nazarius; Byarugaba, WilsonIodine deficiency disorders (IDD) cover a variety of pathological conditions including goitre, mental retardation and perinatal mortality in millions of individuals globally. IDD was initially identified as a problem in 1970 and was confirmed in 1991. In 1993, the Uganda government introduced a policy of Universal Salt Iodization (USI) requiring all household salt to be iodized. After 5 years this study evaluates the USI programme. Objectives: To determine goitre prevalence rate, establish the proportion of household consuming iodized salt and determine the levels of iodine intake in the sample districts. Methods: A sample of 2880 school children aged 6-12 years from 72 Primary schools in 6 districts of Uganda was studied in October 1999. Goitre was established by palpation, salt iodine was analysed by thiosulphate titration, while urinary iodine was analyzed using ICCIDD recommended method F in which iodine is detected colorimetrically at 410nm. Results: The over all total goitre rate was 60.2% down from 74.3 in 1991 and visible goitre was 30% down from 39.2% in 1991. The propotion of households taking adequately iodized salt was 63.8% and the median urinary iodine was 310μg/L. Whereas 36% of 95 urine samples analysed in 1991 had urinary iodine below 50μg/L, only 5% of the 293 urine samples studied in 1999 had the same urine levels. This represents a considerable improvement in iodine intake which is confirmed by the fact that 63.8% of the study households consume adequately iodized salt. If maintained and evenly spread, this will enable Uganda to control IDD. Conclusion: USI has improved iodine intake in Uganda. However, iodine malnutrition is still a severe public health problem because some communities in this study such as in Kisoro still have low iodine consumption, while others such as Luwero now have iodine excess. The latter is likely to predispose to hyperthyroidism.Item A Pepsin-Revealed Material Possibly Related to Chromosomal Banding(Chromosoma, 1978) Byarugaba, WilsonThe enzymes pepsin, c~-chymotrypsin, trypsin, RNase and DNase were applied to preparations of human metaphase chromosomes before staining to study whether dissociable materials related to the formation of G-, Q- and C-bands would be seen. Treatment with active pepsin but not the other enzymes revealed material with ribonucleo-protein properties which dissociated from the chromosomes and formed a halo. - Lateral extensions from the chromatids stretched to the rim of the halo and appeared at positions corresponding to G-bands. A G-band may be defined as a ring of stable chromatid-matrix binding at positions where the chromatids coil to form lateral extensions.Item Solubility tests and the peripheral blood film method for screening for sickle-cell disease: A cost benefit analysis(South African Medical Journal, 2009) Okwi, Andrew Livex; Ocaido, Michael; Byarugaba, Wilson; Magala Ndugwa, Christopher; Parkes, ArthurTo determine the cost benefit of screening for sicklecell disease among infants at district health centres in Uganda using sickling, solubility tests and the peripheral blood film method. Methods. Pilot screening services were established at district health centres. Cost benefit analysis (CBA) was performed in four scenarios: A1 – where there are no sickle-cell screening services at district health centres and all children are referred either to Mulago national referral hospital or A2 – a regional hospital for haemoglobin (Hb) electrophoresis; B1 – when there are screening services at district health centres, only positive samples are taken either to Mulago Hospital or B2 – the regional hospital for confirmation using haemoglobin electrophoresis. Calculations were done in Uganda shillings (USh).Item Targeting wild-type Erythrocyte receptors for Plasmodium falciparum and vivax Merozoites by Zinc Finger Nucleases In- silico: Towards a Genetic Vaccine against Malaria(Genetic Vaccines and Therapy, 2012) Kajumbula, Henry; Byarugaba, Wilson; Wayengera, MisakiMalaria causes immense human morbidity and mortality globally. The plasmodium species vivax and falciparum cause over 75 % clinical malaria cases. Until now, gene-based strategies against malaria have only been applied to plasmodium species and their mosquito-vector. Merozoites of these two respective plasmodium species target and invade red blood cells (RBCs) by using the duffy antigen receptor for chemokines (DARC), and Sialic Acid (SLC4A1) residues of the O-linked glycans of Glycophorin A. RBCs of naturally selected duffy-negative blacks are resistant to P.vivax tropism. We hypothesized that artificial aberration of the host-pathway by target mutagenesis of either RBC –receptors, may abolish or reduce susceptibility of the host to malaria. As a first step towards the experimental actualization of these concepts, we aimed to identify zinc finger arrays (ZFAs) for constructing ZFNs that target genes of either wild-type host-RBC- receptors.Item An up-date on the prevalence of sickle cell trait in Eastern and Western Uganda(BMC Blood Disorders, 2010) Okwi, Andrew L.; Byarugaba, Wilson; Ndugwa, Christopher M.; Parkes, Arthur; Ocaido, Michael; Tumwine, James K.The first survey on sickle cell disease (SCD) done in Uganda in 1949, reported the district of Bundibugyo in Western Uganda to have the highest sickle cell trait (SCT) prevalence (45%). This is believed to be the highest in the whole world. According to the same survey, the prevalence of SCT in the districts of Mbale and Sironko in the East was 20-28%, whilst the districts of Mbarara and Ntungamo in the West had 1-5%. No follow-up surveys have been conducted over the past 60 years. SCA accounts for approximately 16.2% of all pediatric deaths in Uganda. The pattern of SCT inheritance, however, predicts likely changes in the prevalence and distribution of the SCT. The objective of the study therefore was to establish the current prevalence of the SCT in Uganda. Methods: This study was a cross sectional survey which was carried out in the districts of Mbale and Sironko in the Eastern, Mbarara/Ntungamo and Bundibugyo in Western Uganda. The participants were children (6 months-5 yrs). Blood was collected from each subject and analyzed for hemoglobin S using cellulose acetate Hb electrophoresis. Results: The established prevalence of the SCT (As) in Eastern Uganda was 17.5% compared to 13.4% and 3% in Bundibugyo and Mbarara/Ntungamo respectively. 1.7% of the children in Eastern Uganda tested positive for haemoglobin ss relative to 3% in Bundibugyo, giving gene frequencies of 0.105 and 0.097 for the recessive gene respectively. No ss was detected in Mbarara/Ntungamo. Conclusions: A shift in the prevalence of the SCT and ss in Uganda is notable and may be explained by several biological and social factors. This study offers some evidence for the possible outcome of intermarriages in reducing the incidence of the SCT.