『古新聖経』の研究 [論文要旨及び審査の要旨]

関西大

Senataxin, defective in ataxia oculomotor apraxia type 2, is involved in the defense against oxidative DNA damage.

A defective response to DNA damage is observed in several human autosomal recessive ataxias with oculomotor apraxia, including ataxia-telangiectasia. We report that senataxin, defective in ataxia oculomotor apraxia (AOA) type 2, is a nuclear protein involved in the DNA damage response. AOA2 cells are sensitive to H2O2, camptothecin, and mitomycin C, but not to ionizing radiation, and sensitivity was rescued with full-length SETX cDNA. AOA2 cells exhibited constitutive oxidative DNA damage and enhanced chromosomal instability in response to H2O2. Rejoining of H2O2-induced DNA double-strand breaks (DSBs) was significantly reduced in AOA2 cells compared to controls, and there was no evidence for a defect in DNA single-strand break repair. This defect in DSB repair was corrected by full-length SETX cDNA. These results provide evidence that an additional member of the autosomal recessive AOA is also characterized by a defective response to DNA damage, which may contribute to the neurodegeneration seen in this syndrome

Agroecological farming impacts on livelihoods improvement to inform county government on enactment of agroecology policy : case study of Kiambu County, Central Kenya

The basis for the recognition, adoption and provision of an agroecology legal framework relies on the capacity of the existing agroecological systems to provide enough evidence on their effectiveness. Policymaking in Kenya is moving towards evidence-based policies; hence for agroecology to be recognized, documentation of its current systems is in need. To support the transition to agroecology and influence agroecology policy adoption, a study was carried out in Kiambu, a county in Central Kenya. The purpose of the study was to document the effectiveness of agroecological practices and use the results in agroecology policy advocacy work. From the study objectives, agroecology principles and dimensions, and opinions of the local agroecological promoters, a set of 16 indicators were used to investigate the effectiveness of agroecology under the five key dimensions: Economy, Health and Nutrition, Environment and Climate Change, Society and Culture, and Governance. According to FAO of the United Nations, the five dimensions are the priority areas for agricultural policymakers and are relevant in evaluating sustainable food systems. Different semi-structured questionnaires for farmers, government extension officers, NGOs field officers and county assembly members were designed to collect data. Farmers interviewed were only from Kiambu, while some agroecology promoters were from outside Kiambu. Through agroecological farmers networks, women and youth empowerment, knowledge dissemination and sharing increased. A good increase to average increase was recorded on farm productivity, wealth creation, food security, nutrition, mitigation of climate change and environmental conservation. Land size and tenure systems were significant determinants of the type of AEP to be adopted. These positive changes were associated with AEP practices such as diversification, local trading, connectivity, local-based innovations, agroforestry, minimum tillage, integrated pest management (friendly biopesticides, mixed cropping), manuring and biogas production. The study results are consistent with many other practical and theoretical case studies that have mentioned or shown the facilitation of agroecology in improving farmers and the larger community’s livelihood. The ability of agroecology to provide solutions to the above issues is a direct call for its recognition through promotion, the transition of farms and adoption in agricultural policies and strategies. These results provided a fundamental basis for evidence-based discussions supporting agroecology policy. However, agroecological practices need to be scaled up to enable local to regional applicability and policy contexts.M-A

Differential Association of Gene Content Polymorphisms of Killer Cell Immunoglobulin-Like Receptors with Placental Malaria in HIV− and HIV+ Mothers

Pregnant women have abundant natural killer (NK) cells in their placenta, and NK cell function is regulated by polymorphisms of killer cell immunoglobulin-like receptors (KIRs). Previous studies report different roles of NK cells in the immune responses to placental malaria (PM) and human immunodeficiency virus (HIV-1) infections. Given these references, the aim of this study was to determine the association between KIR gene content polymorphism and PM infection in pregnant women of known HIV-1 status. Sixteen genes in the KIR family were analyzed in 688 pregnant Kenyan women. Gene content polymorphisms were assessed in relation to PM in HIV-1 negative and HIV-1 positive women, respectively. Results showed that in HIV-1 negative women, the presence of the individual genes KIR2DL1 and KIR2DL3 increased the odds of having PM, and the KIR2DL2/KIR2DL2 homozygotes were associated with protection from PM. However, the reverse relationship was observed in HIV-1 positive women, where the presence of individual KIR2DL3 was associated with protection from PM, and KIR2DL2/KIR2DL2 homozygotes increased the odds for susceptibility to PM. Further analysis of the HIV-1 positive women stratified by CD4 counts showed that this reverse association between KIR genes and PM remained only in the individuals with high CD4 cell counts but not in those with low CD4 cell counts. Collectively, these results suggest that inhibitory KIR2DL2 and KIR2DL3, which are alleles of the same locus, play a role in the inverse effects on PM and PM/HIV co-infection and the effect of KIR genes on PM in HIV positive women is dependent on high CD4 cell counts. In addition, analysis of linkage disequilibrium (LD) of the PM relevant KIR genes showed strong LD in women without PM regardless of their HIV status while LD was broken in those with PM, indicating possible selection pressure by malaria infection on the KIR genes

Effects of transmission reduction by insecticide-treated bed nets (ITNs) on parasite genetics population structure: I. The genetic diversity of Plasmodium falciparum parasites by microsatellite markers in western Kenya.

Background: Insecticide-treated bed nets (ITNs) reduce malaria transmission and are an important prevention tool. However, there are still information gaps on how the reduction in malaria transmission by ITNs affects parasite genetics population structure. This study examined the relationship between transmission reduction from ITN use and the population genetic diversity of Plasmodium falciparum in an area of high ITN coverage in western Kenya. Methods: Parasite genetic diversity was assessed by scoring eight single copy neutral multilocus microsatellite (MS) markers in samples collected from P. falciparum-infected children (< five years) before introduction of ITNs (1996, baseline, n = 69) and five years after intervention (2001, follow-up, n = 74). Results: There were no significant changes in overall high mixed infections and unbiased expected heterozygosity between baseline (%MA = 94% and He = 0.75) and follow up (%MA = 95% and He = 0.79) years. However, locus specific analysis detected significant differences for some individual loci between the two time points. Pfg377 loci, a gametocyte-specific MS marker showed significant increase in mixed infections and He in the follow up survey (%MA = 53% and He = 0.57) compared to the baseline (%MA = 30% and He = 0.29). An opposite trend was observed in the erythrocyte binding protein (EBP) MS marker. There was moderate genetic differentiation at the Pfg377 and TAA60 loci (FST = 0.117 and 0.137 respectively) between the baseline and post-ITN parasite populations. Further analysis revealed linkage disequilibrium (LD) of the microsatellites in the baseline (14 significant pair-wise tests and IS A = 0.016) that was broken in the follow up parasite population (6 significant pairs and IS A = 0.0003). The locus specific change in He, the moderate population differentiation and break in LD between the baseline and follow up years suggest an underlying change in population sub-structure despite the stability in the overall genetic diversity and multiple infection levels. Conclusions: The results from this study suggest that although P. falciparum population maintained an overall stability in genetic diversity after five years of high ITN coverage, there was significant locus specific change associated with gametocytes, marking these for further investigation

Assessment of molecular markers for anti-malarial drug resistance after the introduction and scale-up of malaria control interventions in western Kenya

Background Although it is well known that drug pressure selects for drug-resistant parasites, the role of transmission reduction by insecticide-treated bed nets (ITNs) on drug resistance remains unclear. In this study, the drug resistance profile of current and previous first-line anti-malarials in Kenya was assessed within the context of drug policy change and scale-up of ITNs. National first-line treatment changed from chloroquine (CQ) to sulphadoxine-pyrimethamine (SP) in 1998 and to artemether-lumefantrine (AL) in 2004. ITN use was scaled-up in the Asembo, Gem and Karemo areas of western Kenya in 1997, 1999 and 2006, respectively. Methods Smear-positive samples (N = 253) collected from a 2007 cross-sectional survey among children in Asembo, Gem and Karemo were genotyped for mutations in pfcrt and pfmdr1 (CQ), dhfr and dhps (SP), and at pfmdr-N86 and the gene copy number in pfmdr1 (lumefantrine). Results were compared among the three geographic areas in 2007 and to retrospective molecular data from children in Asembo in 2001. Results In 2007, 69 and 85% of samples harboured the pfmdr1-86Y mutation and dhfr/dhps quintuple mutant, respectively, with no significant differences by study area. However, the prevalence of the pfcrt-76T mutation differed significantly among areas (p <0.02), between 76 and 94%, with the highest prevalence in Asembo. Several 2007 samples carried mutations at dhfr-164L, dhps-436A, or dhps-613T. From 2001 to 2007, there were significant increases in the pfcrt-76T mutation from 82 to 94% (p <0.03), dhfr/dhps quintuple mutant from 62 to 82% (p <0.03), and an increase in the septuple CQ and SP combined mutant haplotype, K 76 Y 86 I 51 R 59 N 108 G 437 E 540 , from 28 to 39%. The prevalence of the pfmdr1-86Y mutation remained unchanged. All samples were single copy for pfmdr1. Conclusions Molecular markers associated with lumefantrine resistance were not detected in 2007. More recent samples will be needed to detect any selective effects by AL. The prevalence of CQ and SP resistance markers increased from 2001 to 2007 in the absence of changes in transmission intensity. In 2007, only the prevalence of pfcrt-76T mutation differed among study areas of varying transmission intensity. Resistant parasites were most likely selected by sustained drug pressure from the continued use of CQ, SP, and mechanistically similar drugs, such as amodiaquine and cotrimoxazole. There was no clear evidence that differences in transmission intensity, as a result of ITN scale-up, influenced the prevalence of drug resistance molecular markers

Genetic diversity of Plasmodium falciparum parasite by microsatellite markers after scale-up of insecticide-treated bed nets in western Kenya

Background: An initial study of genetic diversity of Plasmodium falciparum in Asembo, western Kenya showed that the parasite maintained overall genetic stability 5 years after insecticide-treated bed net (ITN) introduction in 1997. This study investigates further the genetic diversity of P. falciparum 10 years after initial ITN introduction in the same study area and compares this with two other neighbouring areas, where ITNs were introduced in 1998 (Gem) and 2004 (Karemo). Methods: From a cross-sectional survey conducted in 2007, 235 smear-positive blood samples collected from children ≤15-year-old in the original study area and two comparison areas were genotyped employing eight neutral microsatellites. Differences in multiple infections, allele frequency, parasite genetic diversity and parasite population structure between the three areas were assessed. Further, molecular data reported previously (1996 and 2001) were compared to the 2007 results in the original study area Asembo. Results: Overall proportion of multiple infections (M A ) declined with time in the original study area Asembo (from 95.9 %-2001 to 87.7 %-2007). In the neighbouring areas, M A was lower in the site where ITNs were introduced in 1998 (Gem 83.7 %) compared to where they were introduced in 2004 (Karemo 96.7 %) in 2007. Overall mean allele count (M AC ~ 2.65) and overall unbiased heterozygosity (H e ~ 0.77) remained unchanged in 1996, 2001 and 2007 in Asembo and was the same level across the two neighbouring areas in 2007. Overall parasite population differentiation remained low over time and in the three areas at F ST < 0.04. Both pairwise and multilocus linkage disequilibrium showed limited to no significant association between alleles in Asembo (1996, 2001 and 2007) and between three areas. Conclusions: This study showed the P. falciparum high genetic diversity and parasite population resilience on samples collected 10 years apart and in different areas in western Kenya. The results highlight the need for long-term molecular monitoring after implementation and use of combined and intensive prevention and intervention measures in the region

Issues and challenges in implementing quality assurance in higher education – Strathmore University case

Regional Eastern Africa Unistaff Alumni Network Conference and Workshop – 6th to 10th November Kenyatta University.This paper deals with the issues and challenges facing the successful implementation of a QMS in an educational institution, namely, Strathmore University. It looks at the various steps followed to implement QMS in the University. Strathmore University (SU) decided to implement a quality assurance system in early 2003 to ensure excellence in the pursuit of its objectives. In the development of her strategic plan, the University identified the need to institute a QMS to ensure adherence to quality along the expansion path. It was a means of entrenching a systematic approach to quality management in both its administrative and academic functions. Ideally, the QMS should guarantee adherence to the University’s processes and procedures. The process of QMS entails various steps including the decision to implement quality assurance, making of quality related choices, educating staff, constituting the implementation team, defining statements, policies and processes, documentation, internal audit training and the audit process, certification and QMS monitoring and growth. The paper discusses the various challenges encountered in the steps of the QMS process. It further looks at positive and negative aspects of each step as well as the measures taken to overcome them. In conclusion, an understanding of the issues and challenges at each step of QMS implementations allows for suitable preventive and correcting actions to achieve optimal performance over time. Our conclusion would be of high interest to other local and regional universities who have decided to implement a QMS.This paper deals with the issues and challenges facing the successful implementation of a QMS in an educational institution, namely, Strathmore University. It looks at the various steps followed to implement QMS in the University. Strathmore University (SU) decided to implement a quality assurance system in early 2003 to ensure excellence in the pursuit of its objectives. In the development of her strategic plan, the University identified the need to institute a QMS to ensure adherence to quality along the expansion path. It was a means of entrenching a systematic approach to quality management in both its administrative and academic functions. Ideally, the QMS should guarantee adherence to the University’s processes and procedures. The process of QMS entails various steps including the decision to implement quality assurance, making of quality related choices, educating staff, constituting the implementation team, defining statements, policies and processes, documentation, internal audit training and the audit process, certification and QMS monitoring and growth. The paper discusses the various challenges encountered in the steps of the QMS process. It further looks at positive and negative aspects of each step as well as the measures taken to overcome them. In conclusion, an understanding of the issues and challenges at each step of QMS implementations allows for suitable preventive and correcting actions to achieve optimal performance over time. Our conclusion would be of high interest to other local and regional universities who have decided to implement a QMS

Unique Cryptosporidium Population in HIV-Infected Persons, Jamaica

A cryptosporidiosis survey showed the presence of Cryptosporidium hominis, C. parvum, C. canis, and C. felis in 25, 7, 1, and 1 HIV-positive persons from Jamaica, respectively; 1 person had both C. hominis and C. felis. Multilocus sequence typing indicated the presence of a homogeneous but geographically distinct C. hominis population in Jamaica

Pattern of road traffic fatalities in Nairobi

Background: Road traffic injuries continue to exert a huge burden on Kenya’s healthcare services. Over 134,000 crashes occur on the Kenyan roads killing more than 2,600 and seriously injuring 11,000 people annually. Injury pattern among traffic trauma admissions have been recently described while that of fatalities remains unstudied. Serious injuries will continue to result from road collisions as long as the compliance to traffic rules remains poor, the rates of seat belt use is low and the number of pedestrian walkways and flyovers few. Objective: To determine the pattern of fatal injuries from road traffic collisions in the city of Nairobi. Design: This was a prospective descriptive study. Setting: Kenyatta National Hospital (KNH) and the Nairobi City Mortuary. Subjects: One hundred consecutive road traffic fatalities autopsied between April 2003 and January 2004 (90 KNH Mausoleum, 10 Nairobi City Mortuary). Results: Casualties included 81 males and 19 females with an age range of 4-80 years and a median age of 33.5 years. Forty-five percent arrived at casualty dead while the remainder were admitted for a mean period of 14 days. The main road-user groups involved were pedestrians (62%), passengers (24%) and drivers (9%). A majority (72%) were injuries sustained along major highways. Head trauma was the most common form of injury accounting for 76%, followed by chest injuries 70%, abdominal injuries 60%, lower limb injuries 56%, upper limb injuries 35%, neck injuries 29% and pelvic injuries 24%. Head, abdominal and chest injuries accounted for 57%, 17% and 13% of causes of death respectively. Limb injury was the least common cause of mortality, although it may have complicated some of the other injuries. Conclusion: Road traffic fatalities are predominantly a pedestrian problem. Head and trunk injuries account for 87% of the deaths. Provision of pedestrian walkways and flyovers along major highways may protect the vulnerable pedestrian population. Improvement of immediate emergency services able to cope with head and trunk injuries is recommended