Antigen-specific memory T cell distribution in non-lymphoid tissue

Thesis (S.M.)--Massachusetts Institute of Technology, Biological Engineering Division, 2007.Includes bibliographical references (leaves 28-34).CD8+ T cells are the main adaptive immune system cell type responding to intracellular pathogens, particularly viruses, and tumor antigens. In the case of influenza, activated T cells migrate from the mediastinal (draining) lymph nodes to the lung where they perform their cytolytic function. After pathogen clearance, memory CD8+ T cells are generated, giving rise to long-term protection from reinfection. However, these cells are no longer detectable in the lung parenchyma six months post-infection, and cell-mediated immunity, and protection is lost. Knock-out studies in mice show that interleukin 15 (IL-15) is essential for memory CD8+ T cell proliferation. Fibroblasts, macrophages, dendritic cells and epithelial cells express IL-15 and its receptor isoform [alpha] (IL-15R[alpha]). Histological studies suggest that memory CD8+ T cells preferentially reside in peribronchiolar and perivascular areas, the stroma, of the lung. We hypothesize that memory CD8+ T cells preferentially reside in regions where molecules necessary for their maintenance, for example, IL-15/R secreting cells, are located. In this study, we have shown that antigen-specific 2C GFP effector memory CD8+ T cells are generated in B6 recipient mice 30-32 days after influenza virus infection, preferentially reside in peribronchiolar areas. Both 2C and 2C GFP recipient mice have severe vasculitis and widely distributed inflammatory infiltrates 7 days post-infection. Lower lung lobes appear to be more affected than upper lobes at this time point. On day 30, most of the airways have been cleared and restored. Although lymphoid-appearing nodules were detected in the lungs 31 dpi, no clusters of B cells and T cells suggesting induced BALT were identified by immunofluorescence.(cont.) Interestingly, antigen-specific GFP cells preferentially remained in the lung tissue and were almost undetectable in spleens, lymph nodes, and livers. This preference was not observed in 2C (non-GFP) recipient mice. Immunofluorescence studies showed no colocalization between 2C GFP T cells and dendritic cells that might suggest stable dendritic cell interactions contribute to antigen-specific cells preferentially residing in the lung stroma. Further studies are necessary to determine what other cell types might contribute to this phenomenon. These results provide some insight into how structural elements in non-lymphoid tissue influence cell-mediated immunity.by Mobolaji O. Olurinde.S.M

Pseudo-goldstino to gravitino decay : an implication of multiple supersymmetry breaking

Thesis (S.B.)--Massachusetts Institute of Technology, Dept. of Physics, 2013.Cataloged from PDF version of thesis.Includes bibliographical references (pages 67-68).This thesis studies the decay of a pseudo-goldstino to a gravitino plus a photon in the Minimal Supersymmetric Standard Model. The foundational premise of this decay process is that there are two independent sectors of supersymmetry breaking. We compute this main decay rate using the goldstino equivalence theorem to replace the final gravitino state with a goldstino. This replacement allows us to study simpler models which help build the intuition and methods for the final calculation. Specifically, we first study the decay of a pseudo-goldstino to a goldstino plus a photon in a toy model of multiple supersymmetry breaking and then the same process in the Minimal Supersymmetric Standard Model without supergravity. Incorporating supergravity introduces the interpretation of the goldstino as the longitudinal component of the gravitino and introduces the constant mass ratio between the gravitino and the pseudo-goldstino which is definitive of multiple local supersymmetry breaking. For the main decay process, we find that the rate is zero for certain relationships between the parameters which define the two hidden sectors. In the discussion we suggest other similar calculations which can be done within the same framework.by Mobolaji Williams.S.B

Quantitative analysis of a stochastic SEITR epidemic model with multiple stages of infection and treatment

We present a mathematical analysis of the transmission of certain diseases using a stochastic susceptible-exposed-infectious-treated-recovered (SEITR) model with multiple stages of infection and treatment and explore the effects of treatments and external fluctuations in the transmission, treatment and recovery rates. We assume external fluctuations are caused by variability in the number of contacts between infected and susceptible individuals. It is shown that the expected number of secondary infections produced (in the absence of noise) reduces as treatment is introduced into the population. By defining RT,n and ℛT,n as the basic deterministic and stochastic reproduction numbers, respectively, in stage n of infection and treatment, we show mathematically that as the intensity of the noise in the transmission, treatment and recovery rates increases, the number of secondary cases of infection increases. The global stability of the disease-free and endemic equilibrium for the deterministic and stochastic SEITR models is also presented. The work presented is demonstrated using parameter values relevant to the transmission dynamics of Influenza in the United States from October 1, 2018 through May 4, 2019 influenza seasons

Breast cancer receptor status assessment and clinicopathological association in Nigerian women: A retrospective analysis

Background: Breast cancer markers are becoming increasingly important in breast cancer research due to their impact on prognosis, treatment and survival. The present retrospective study was carried out to quantify the proportion of estrogen (ER), progesterone (PR), and human epithelial receptor 2 (HER2) expressions and their association with tumour grade, age, and tumour size in breast cancer patients in Nigeria. Materials and methods: The paraffin embedded tissue sections were analysed for breast cancer markers using monoclonal antibody SP1 for ER and SP2 for PR and polyclonal antibody ErbB2 for HER2. Results: A total of 286 breast cancer paraffin wax tissue sections were analysed for ER, PR and HER2 expression. Of all the tissue samples examined, 20 (7%) were ER-positive, 6 (2.1%) were PR-positive, 11 (3.8%) were HER2-positive whereas 248 (87%) were triple-negative breast carcinoma. ER- and PR-positivity was associated with early grade I and II tumours (P 50mm (P < 0.0001). Conclusion: A small proportion of Nigerian women with breast cancer are ER/PR-positive which are associated with less aggressive, better prognosis and benefit from endocrine therapy. An even smaller proportion of patients with aggressive tumors were HER2-posivite but responsive to Herceptin treatment. Unfortunately, a very high proportion of cases were triple-negative which is associated with very aggressive tumours and no targeted treatment, which may explain the high mortality rates from breast cancer in Nigeri

Factors contributing to T cell persistence in a tolerizing tumor environment

Thesis (Ph. D.)--Harvard-MIT Division of Health Sciences and Technology, 2010.Cataloged from PDF version of thesis.Includes bibliographical references.Cancer is a leading cause of death worldwide, accounting for at least 10% of all deaths globally. Current therapies for cancer include surgical excision, chemotherapy and immunotherapy. CD8[+] T cells are adaptive immune cells responsible for eradicating tumor cells. However, these T cells can be rendered ineffective through tolerance. Yet in various mouse models and human patients, tolerant T cells persist. The aim of this project is to identify factors that support T cell persistence in a tolerizing tumor environment. Using a spontaneous prostate cancer model, we study antigen-specific T cells that have been shown to be locally tolerant in the prostate tumor environment. In this thesis, I compare the immune response in normal, antigen bearing, tumor transgenic and tumor-antigen transgenic mouse models. Results show that T cell infiltration and persistence in the tolerizing prostate environment is dependent on the presence of antigen and tumorigenic/tumor-related factors. Although antigen-specific T cells are locally tolerant in the prostate of tumor-antigen transgenic mice, they generally persist in the prostates of tumor transgenic mice regardless of whether antigen is present or not. Further analyses revealed that T cells infiltrate the prostate and can proliferate extensively in the tolerizing tumor environment due to the presence of antigen. Interestingly, antigen-specific T cells are depleted from the spleens of mice that express antigen in their prostates.(cont.) This depletion from the spleen is correlated with low levels of IL-7R[alpha] expression and the presence of antigen in the prostate. Tumorigenic or tumor-related factors in the prostate also appear to be supporting CD8[+] T cell persistence. This thesis shows that persistence of antigen-specific T cells in the tumor environment is not dependent on IL-15 and IL-7; cytokines known to support proliferation and maintenance of persisting functional CD8[+] T cells. Some potential candidates are also discussed. More investigative work needs to be done to identify the role of these factors on T cell infiltration and persistence. In combination with tolerance-breaking strategies, persisting T cells may be excellent vehicles for delivering site-specific cancer immunotherapy.by Mobolaji 0. Olurinde.Ph.D

A SURVEY OF VETERINARY DRUGS IN USE IN FISH FARMS IN ABEOKUTA, OGUN STATE. NIGERIA

A cross-sectional study was conducted to characterize fish farmers in Ogun State with respect to their use of veterinary drugs and awareness of adverse effects these drugs have on human. A semi structured questionnaire was used to gather relevant data from 80 fish farmers in Abeokuta. The findings indicated that fish farmers in the study area were mostly males, married and well educated. Most of them obtain primary source of income from fish farming. Despite the fact that both skilled (41.25%) and unskilled (58.75%) labourers were employed on the farms, family members were also involved in the production. 21.25% used pelmendazole, 10.0% used melbendazole, while 26.0% used ivermectin as their anthelminthics. 78.75% used oxytetracycline, 37.5% used penicillin, while 40% used sulfadimidine as their antibiotics. 67.5% used ovaprim®&nbsp; while 42.5% used ovatide® as hormones to boost their fish production. 76.25% of the fish farmers do not involve veterinarians in the production, whilst 48.75% of the farmers are not aware of adverse effect of veterinary drug residue in human. The results are discussed in view of the need for more involvement of veterinarians in fish production to ensure the adoption of global standards, thus guaranteeing improved food safety and sustainability in fish production. &nbsp; &nbsp; &nbsp

Chemical and biological significance of naturally occurring additives on African black soap and its performance

The potassium ester (C11H23COO-K+) commonly known as African black soap was prepared by the action of palm kernel oil on cocoa pods. This was divided into four portions. Sample A contained the African Black soap without any modification, sample B was black soap modified with honey, sample C and sample D were modified with shear butter and coconut oil respectively. The pH, FTIR and phytochemical analyses of the samples were carried out. They were also screened for in-vitro antibacterial activities against two Gram-positive bacteria (Staphylococcus aureus and Bacillus subtilis) and two Gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli). The pH determinations showed that all the samples were alkaline in nature with sample A having the lowest pH of 8.90, while sample B had the highest pH of 9.58. FTIR analyses of sample A revealed strong bands assigned to the υ (C=O) frequency of a keto group at 1668 and 1560 cm-1 and a strong band at 1379 cm-1 assigned to the υ (C-O) frequency of the ester oxygen. The spectra of samples B, C and D showed no complexation through these oxygen donor atoms, but rather some interactions with other present molecules. Phytochemical analyses showed that samples A and D were rich in saponin, all the samples were rich in both flavonoids and terpenoids, while tannins and steroids were absent in all the samples. Antimicrobial studies showed that only sample B was active against Staphylococcus aureus, while samples A, C and D were inactive against all tested microorganisms.Keywords: Additives, African Black Soap, Phytochemical and Antimicrobia

Socioeconomic inequalities and family planning utilization among female adolescents in urban slums in Nigeria

Background/statement of problem: Family planning (FP) utilization is important for preventing unwanted pregnancy and achieving optimal reproductive health. However, the modern contraceptive prevalence rate (mCPR) among women of childbearing age is still low in many low- and middle-income countries (LMIC), particularly in Nigeria, despite interventions to increase access and utilization. The low mCPR has been associated with a high prevalence of unwanted pregnancy, unsafe abortion, sexually transmitted infections such as HIV/AIDS, and high maternal and infant mortality in LMIC. Despite existing studies associating high family planning utilization to urban settings relative to the rural areas, the socioeconomic inequality in urban settings, especially among adolescents in urban slums has been given less research attention. This study examines the role of socioeconomic inequality on family planning utilization among female adolescents of various ethnic backgrounds in urban slums in Nigeria. Methods: The study utilized data from the Adolescent Childbearing Survey (2019). A total sample of 2,035 female adolescents of ages 14-19 years who were not pregnant at the time of the study and were resident in selected slums. Associations between socioeconomic inequalities-measured by wealth index, social status, and education-and modern contraceptive use were examined using relative and slope inequality indices, and logistic regression models. Results: The results show that only 15% of the female adolescents in the North, and 19% in the South reported modern contraceptive use. While wealth index and education were important predictors of FP use among adolescents in southern urban slums, only education was important in the North. However, the relative and slope inequality indices further indicate that adolescents with no education and those in the lowest social status group use much fewer contraceptives compared to their counterparts with higher wealth and social statuses. Those with secondary/higher education and the highest social status group, respectively, were more disadvantaged in terms of FP utilization (Education: RII = 1.86, p < 0.05; 95% C.I. = 1.02-2.71; Social Status: RII = 1.97, p < 0.05; 95% C.I. = 1.26-2.68) with results showing a more marked level of disparity when disaggregated by North and South. Conclusion: The persistent socioeconomic inequalities among female adolescents in Nigeria, especially those in the urban slums, have continued to limit their utilization. Policy measure in education, communication and subsidized contraceptives should be intensified for vulnerable female adolescents in the slums

Climate Change and Economic Development in Sub-Saharan African Countries: A Panel Econometric Approach

This paper attempts to empirically investigate the impact of climate change on economic development in Sub-Saharan African countries. It is a simple linear panel model using three estimation techniques, fixed effect, random effects and Maximum likelihood method. The Hausman test was also conducted to choose the most appropriate technique. In all, the paper finds that climate change impacts positively on the economic development in the region. The paper further recommends more adaptation as against mitigation measures, as many SSA countries already have some forms of indigenous adaptation measures which are relatively more manageable and less costly technological options in dealing with climate change. KEY WORDS: Climate, economic development, Afric

Factors associated with caregiver burden in a child and adolescent psychiatric facility in Lagos, Nigeria: a descriptive cross sectional study

<p>Abstract</p> <p>Background</p> <p>Definitions of burden of care stress the effect of the patient's mental illness on the family. There are generally very few studies in this environment on caregiver burden in child/adolescent mental ill-health. This study aimed to identify patient and caregiver characteristics that are associated with caregiver burden.</p> <p>Method</p> <p>Caregivers of patients attending the Child and Adolescent Clinic of the Neuropsychiatric Hospital, Yaba, Lagos [n = 155] were consecutively recruited over a one-month period. The caregivers were administered a sociodemographic questionnaire, the General Health Questionnaire, Zarit Burden Interview, and the Columbia Impairment Scale. Scoring on the Children's Global Assessment Scale was done by clinicians.</p> <p>Results</p> <p>Most caregivers observed in this study were females (80.5%), with mothers of the patients accounting for 78% of all the caregivers. A higher percentage of the patients were males (52.8%). Moderate to severe/severe burden was recorded among 25.2% of caregivers. Factors associated with caregiver burden were patient's level of functioning [r = 0.489, p < 0.001], psychiatric morbidity in the caregiver [r = 0.709, p < 0.001], level of impairment as assessed by the caregiver [r = 0.545, p < 0.001], and child's level of education [t = 3.274, p = 0.001]. Each one independently predicted caregiver burden.</p> <p>Conclusion</p> <p>The study reveals a high level of burden among the caregivers of children and adolescents with mental health problems.</p