학교 조직의 병리 현상 연구 : 학교폭력 축소·은폐 사례를 중심으로

김유원 연세대학교 대학원 2021 국내박사

ㅤA series of negative incidents in schools brings the school organizational health into question. We have long devoted our efforts to improve students' academic performance or personal maturity, but have been relatively negligent in exploring and managing pathologies of schools, which should basically never occur in schools. school health, not school efficiency or effectiveness, can be a more appropriate standard for diagnosing school organizations because outcomes of school education are long-term and school performance difficult to evaluate. Also, school health should receive more attention because a school is likely to survive regardless of its health status, making school members suffer for a long time. Therefore, we revisit the importance of school organizational health by exploring pathological phenomena of school organizations given the fact that health can only be recognized and defined through disease. ㅤThis study aims to examine the overall aspects of organizational pathology of schools, to explore the specific aspects of organizational pathology of schools through the case of the concealment of school violence, and to identify key factors and derive a model of organizational pathology of schools in South Korea based on various philosophical backgrounds of malady. To achieve the goal of this study, three different analyses were conducted sequentially. ㅤThe methods for each analysis and corresponding results are as follows. First, literature review was conducted from the perspective of illness, sickness, and disease to scrutinize the overall aspects of school organizational pathology. Specifically, press reports about whistleblowing in schools, the legislation, auditing standards for schools, and the cases of dismissal of Appeal Commission for Teachers, and Research papers in South Korea major journals dealing with negative aspects of school organization were reviewed. ㅤResults from the literature analysis showed that 'school illness' perceived by school members and 'school sickness' identified by the society shared a number of common requirements, but they rarely overlapped with those of 'school disease' defined by researchers. This emphasizes that researchers should identify internal dynamics of major illegalities and irregularities, including the concealment of school violence that school members and the society request for investigation. ㅤSecond, a qualitative case study was conducted from the perspective of disease to comprehend the specific aspects of school organizational pathology. The qualitative case study includes in-depth interviews with five former and current schoolteachers who have witnessed the case of the concealment of school violence within the past decade and reviews on documentary materials relevant to such issues. ㅤThe qualitative case study identified that the concealment of school violence took place in one of the three formats: school as a whole, school administrator - chief teacher - teacher, or a teacher alone. The cases of the concealment of school violence were revealed to the surface through passive-defensive or offensive-defensive actions. There was a deep-rooted fear in the schools where the concealment of school violence was observed, and this fear led to a feeling of helplessness which, in turn, can appear as an act of immorality. Such human actors’ emotions and behaviors were strengthened through their interactions with non-human actors in various forms of documentation or policies in social and institutional contexts, such as consumerism, deskilling, and deficiency of ethical leadership. ㅤThird, key factors and models of school organizational pathology were explored based on the results from the first two analyses, adopting the perspective of Canguilhem. This study revealed that there was an excessive number of norms assigned to school organization, which rather dampened the normality of schools. We also applied Actor-Network Theory(ANT) and Homeostasis Models to Social-Systems Model for Schools to establish a model for the pathology of school that encompass norms and normality. The results of this study suggest that schools need to develop 'normality' which helps to recognize their own pathology and to self-establish 'norms' on their own facing fear. In addition, to deal with the organizational pathology of schools, our society should diversify channels for whistleblowing and establish policies to protect whistle blowers. Researchers also need to pay a constant attention to this issue. Lastly, specific plans to establish school normality are required to prevent the organizational pathology of schools. ㅤ학교에서 연이어 발생하는 부정적인 사건들은 학교 조직이 과연 건강한지에 대한 의문을 제기한다. 우리는 오랜 시간 동안 학생의 학업성취도 향상이나 인간적 성장을 위한 목표 달성 등에 온 힘을 쏟아 왔지만, 학교라는 조직이 제 목적을 다하기 위해 기본적으로 발생하지 않아야 하는 병폐에 대한 탐색과 관리에 있어서는 상대적으로 소홀하였다. 그러나 학교 교육의 결과는 장기적으로 나타나 성과 평가가 곤란하다는 점에서 조직 진단 기준으로 효율성이나 효과성보다 건강성이 적절하며, 학교는 봉사 조직이자 공공 조직이라는 특성상 조직이 병들어 있더라도 지속적으로 생존·유지되고 있을 확률이 높아 이로 인한 폐해가 오랜 기간 학교 구성원들을 고통스럽게 할 수 있다. 따라서 학교 조직 건강의 중요성에 다시 주목하되, 건강은 질병을 통해서만 인식되어 규정될 수 있다는 점에서 학교 조직의 병리 현상을 우선적으로 탐구하고자 한다. ㅤ이 연구의 목적은 병을 바라보는 다양한 관점에 대한 이해를 바탕으로 하여 우리나라 학교 조직 병리의 전반적 양상을 살펴보고, 학교 조직 병리의 구체적 양상을 학교폭력 축소·은폐 사례를 통해 탐구하며, 이를 바탕으로 학교 조직 병리의 핵심 요인과 모형을 밝히는 데에 있다. ㅤ첫 번째로, 학교 조직 병리의 전반적 양상을 살펴보기 위해 해석주의 관점, 사회구성주의 관점, 실증주의 관점에서 문헌 연구를 수행하였다. 구체적으로는 학교의 내부 고발 혹은 공익 제보에 대한 언론 보도, 법령과 이에 기반을 둔 감사 기준 및 교원소청심사위원회 기각 결정 사례, 국내 학교 조직 관련 주요 학술지에서 부정적 양상을 결과로 다룬 연구 논문을 살펴보았다. ㅤ분석 결과, 학교 구성원들이 호소하는 학교 질환과 사회가 문제시여기는 학교 병약함은 매우 많은 영역을 공유하는 반면, 연구자들이 규명하는 학교 질병의 영역과는 거의 겹치지 않아 연구자들의 학교 병리 탐색이 더 적극적으로 이루어져야 함을 발견하였다. 구체적으로 연구자들은 학교 구성원 및 사회가 문제시하는 학교폭력 축소·은폐를 포함한 주요 불법·비리의 내적 역동에 대해 규명할 필요가 있었다. ㅤ두 번째로, 학교 조직 병리의 구체적 양상을 살펴보기 위해 질병 관점에서 규명될 필요가 있는 학교폭력 축소·은폐에 대한 질적 사례 연구를 수행하였다. 질적 사례 연구는 최근 10년 이내에 학교폭력 축소·은폐 사례를 목격한 경험이 있는 전·현직 학교 교원 5명이 참여한 심층 면담 자료와 기타 사례 관련 문헌 자료로 이루어졌다. ㅤ분석 결과, 학교폭력 축소·은폐는 학교 전체, 학교 관리자-부장-교사, 교사 수준 중 하나의 형태로 이루어지는 경우가 많았으며, 수동-방어적 행동이나 공격-방어적 행동을 통해 표면으로 드러나고 있었다. 그리고 학교폭력 축소·은폐가 발생한 학교 조직에 존재하는 뿌리 깊은 두려움의 정서를 확인할 수 있었고, 두려움과 이로부터 형성되는 무기력은 부도덕함의 행위로 이어질 수 있음을 발견하였다. 이러한 인간 행위자의 정서와 행동은 소비자주권주의, 업무 탈기술화, 윤리적 리더십의 부재와 같은 사회·제도적 맥락 속에서 다양한 문서나 정책의 형태인 비인간 행위자와의 상호작용을 통해 강화되고 있었다. 이 때, 학교폭력 축소·은폐는 학교 및 학교 구성원 특성의 조합에 따라 다양하게 나타나고 있었다. ㅤ세 번째로, 앞의 두 연구 결과와 캉길렘의 병리 관점을 바탕으로 학교 조직 병리의 핵심 요인과 모형에 대한 탐색을 수행한 결과, 규범과 규범성의 개념에 주목할 필요가 있음을 확인하였다. 그리고 학교에 부여되는 규범이 과도하게 많고, 이로 인해 학교의 규범성은 오히려 점점 위축되고 있음을 발견하였다. 그리고 학교 조직의 체제 모형에 행위자 네트워크 이론과 항상성 모형을 적용하여 규범과 규범성 등을 포괄하는 학교 조직의 병리 모델을 수립하였다. ㅤ연구 결과 및 결론은 학교가 스스로 병리를 인지하고 질서를 수립하는 규범성을 기를 수 있도록 지원할 것을 요청한다. 그리고 학교 조직 병리의 치료를 위해 사회 차원의 공익제보 통로 다양화 및 안전 보장의 사회적 장치 마련이 필요하고, 연구자 차원의 학교 조직 병리에 대한 지속적 관심과 연구 누적이 요청되며, 사회 조직 병리의 예방을 위한 학교 규범성 수립의 구체적 방안 모색이 요구된다.

Mechanistic Characterization of the Auto-Inflammatory Pathology Caused by NFκB RelB Deficiency

Navarro, Hector Ivan University of California, Los Angeles ProQuest Dis 2023 해외박사(DDOD)

Autoimmune and inflammatory diseases are leading causes of morbidity and death and arise from highly unique etiologies. Many autoimmune disorders involve dysregulation of the transcription factor NFκB/RelA, termed relopathies, and the interferon signaling pathway, termed interferonopathies. Previous reports have demonstrated that the loss of RelB results in autoimmunity and inflammatory pathology in both pediatric patients and mice. While recent studies reported immune sentinel cells to be critical mediators of the loss of RelB pathology, it remains unknown what dysregulated immune response pathways exist within these cells that drive the loss of RelB pathology.In these studies, I took an unbiased approach to characterize innate responses of immune sentinel cells to determine both the functional role of dysregulated gene programs in the RelB- deficient pathology and the mechanistic regulation of these gene programs by RelB. I found that loss of RelB in patient-derived fibroblasts and mouse myeloid cells results in elevated induction of hundreds of interferon-stimulated genes. To examine their functional role in RelB-deficient pathology, I generated compound mutant mice in which IFN signaling was genetically ablated. Removing hyper-expression of the interferon stimulated gene program did not ameliorate the3autoimmune pathology of RelB knockout mice. Instead, I found that RelB suppresses a smaller set of pro-inflammatory response genes sharing a common NFκB binding motif in a manner that is independent of interferon signaling. Therefore, while transcriptomic profiling would describe the loss of RelB pathology as an interferonopathy, the functional genetic evidence indicates that the pathology in mice is interferon-independent.To further determine the mechanism by which these pro-inflammatory genes were dysregulated by the loss of RelB, I performed biochemical and genome-wide analysis of RNA- Seq and ChIP-Seq data sets from innate immune cells derived from WT and RelB-/- mice. I found that the loss of RelB results in the hyper-binding by RelA to κB sites at or near the TSS of these IFN-independent pro-inflammatory genes, suggesting RelB may inhibit pro-inflammatory gene expression via competition with RelA for target gene promoters. To test this, I generated a novel RelB-DNA binding mutant mouse with three specific mutations in amino acids that contact the κB site. Indeed, while other cytoplasmic functions of RelB remained intact, the directed loss of RelB DNA binding function resulted in the hyper-expression of both IFN-dependent and independent gene expression and phenocopied the loss of RelB-/- inflammatory pathology. These results together suggest a key regulatory mechanism by the NFκB system in innate immune cells, in which RelB functions as a critical regulator of RelA pro-inflammatory gene expression and suppressor of autoimmune pathology.

Neuroinflammation and the Glial Response Contribute to Both Beneficial and Pathological Outcomes in Multiple Disease Models

Cherry, Jonathan D University of Rochester 2015 해외박사(DDOD)

Neuroinflammation has been considered a driver of pathology and cognitive dysfunction for many years; however, not all inflammation results in the same outcome. The brain is sensitive to a wide variety of inflammatory stimuli that can result in different outcomes depending on the type of exposure, environment, and underlying pathological processes. In order to gain a better understanding of the relationship between neuroinflammation and brain pathology, we developed three models comprising unique inflammatory stimuli. The first model aimed to understand how peripheral inflammation contributes to neuroinflammation. To accomplish this, a 10% total body area full thickness thermal burn was used to induce significant peripheral inflammation without lethality. Prior to burn injury, mice were subjected to 0 or 5 Gy whole body gamma radiation. Typically, only doses over 15 Gy are sufficient to induce neuroinflammation, so a possible combinative effect of combination injury was investigated. Mice were followed out to 6 hours, 1 week, or 6 months. Combination injury resulted in a significant elevation of mRNA for both the vascular marker ICAM-1 and the inflammatory marker TNFbeta at 6 hours. Interestingly, combination injury also showed increased IL-6 serum protein levels suggesting elevated peripheral inflammation as well. Furthermore, enhanced glial cell activation by CD68 and Iba1 immunohistochemistry was seen at all time points for the combination injury. Lastly, combination injury lead to significant learning and memory deficits compared to the single injuries alone, suggesting a functional synergy between peripheral inflammation arising from burn and brain radiation injury. In addition to cognitive dysfunction, neuroinflammation has been posited to be a driver of pathology in many diseases. One prominent case is Alzheimer's disease (AD). To explore this relationship, the APP/PS1 AD mouse model was subjected to 0, 10, or 100 cGy 56Fe particle galactic cosmic radiation (GCR). Six months after exposure, irradiated mice showed decreased cognitive abilities. Interestingly, in male mice we observed acceleration of Abeta plaque pathology using Congo red and 6E10 staining, which was confirmed via ELISA. No microglial activation was observed at this time point, but elevated ICAM-1 levels were seen, suggesting a potential vascular mechanism. These two studies suggest that neuroinflammation is a detrimental process leading to cognitive dysfunction and pathology. However, neuroinflammation is a normal response to injury that likely has protective functions. Interestingly, several studies have demonstrated that blocking neuroinflammation does not always mitigate pathology, and in some cases, enhances it. This suggests a more complex nature to neuroinflammation than previously thought. The last model explored these seeming paradoxical findings that in some cases, neuroinflammation can result in amelioration of pathology. Using an adeno-associated viral vector carrying a human IL-1beta cDNA to transduce mice, neuroinflammation was induced in one hippocampus of 8-month-old APP/PS1 mice for 4 weeks, while the other hemisphere received a control viral injection. We observed a robust activation of alternatively activated, anti-inflammatory (M2) microglia using the marker Arg1. This increase in Arg1+ microglia coincided with a reduction in Abeta plaques. Arg1+ microglia were shown to contain Abeta suggesting they were the mechanism of clearance. When IL-4 was used to specifically induce Arg1+ microglia, there was significant plaque reduction. Conversely, blocking induction of Arg1+ microglia during chronic inflammation impaired plaque clearance. Together these findings demonstrate that Arg1+ microglia are necessary and sufficient for Abeta plaque reduction during neuroinflammation. Overall, these three models of neuroinflammation provide a better understanding of how inflammation influences both cognitive function and disease progression. Furthermore, they can guide us towards possible avenues for immunomodulatory therapy of brain disorders.

Affecting factors the Accuracy of preoperative tumor size assessment on MRI in T1 (≤2cm) invasive breast carcinoma

한솔 가천대학교 대학원 2020 국내석사

Purpose: To investigate the factors influencing the MRI-pathology concordance of tumor size in patients with T1 (≤2cm) invasive breast carcinoma. Materials and Methods: Data from 200 histologically confirmed T1 invasive breast carcinomas were analyzed retrospectively. Preoperative breast MRI was reviewed for size, morphology, and dynamic contrast-enhanced tumor kinetics. MRI Tumor size (greatest diameter) was compared to size measurement of tumor at pathology. Concordance was defined as a diameter difference of ≤0.5cm. Clinical features and histological factors for MRI-pathology discordance were investigated. Results: The mean size on MRI was 1.48±0.49cm and the mean value of pathological tumor size 1.40±0.39cm. The overall correlation between pathology and MRI measurements was high (Spearman’s rho=0.740, p<0.01). MRI-pathology concordance was found in 179/200 (89.5%) cases; the size was overestimated in 15 (7.5%) tumors and underestimated in 6 (3%). On univariate analysis, MRI-pathology discordance was associated with human epidermal growth factor receptor type 2 (HER2) positivity (p=0.027). On multivariate analysis, HER2 positivity was significantly influenced MRI-pathology discordance(p<0.05). Conclusions: HER2 positivity was strongly associated with MRI-pathology discordance in T1 invasive breast carcinomas.

Investigation into the effects and mechanisms of rapamycin treatment in two mouse models of Complex I-deficient neurological pathology

Yanos, Melana University of Washington 2014 해외박사(DDOD)

Treatments to stop or reverse the debilitating progression of early- and late-onset neurological diseases remain undiscovered. Collective evidence suggests that inhibition of the mechanistic target of rapamycin (mTOR) signaling pathway is effective at reducing markers of pathology in experimental models of age-related and developmental neurological diseases. These include, but are not limited to, models for Alzheimer's disease, Parkinson's disease, Huntington's disease, Fragile X syndrome, Tuberous Sclerosis Complex and Leigh syndrome. How regulation of mTOR activity and its downstream effectors interact with underlying neural mechanisms of disease has been a topic of considerable debate. The studies presented here investigate the potential therapeutic effects of the mTOR inhibitor rapamycin in two different mouse models for neurological disease: the NDUFS4 knockout (NDUFS4 KO) mouse for Leigh Syndrome and the MPTP mouse model for Parkinson's disease. In these models, mitochondrial electron transport chain complex I activity is reduced but results in distinct patterns of neuronal pathology. Our major objectives were (1) to identify previously unreported effects of rapamycin treatment in these models; and (2) to identify the potential cellular mechanisms that mediate these effects. First, we demonstrate that daily treatment with high dose rapamycin effectively extends the short lifespan of NDUFS4 KO mice. Rapamycin treatment also resulted in prolonged healthspan in KO mice, as indicated by the offset of neurological damage, maintenance of weight and body fat, and the improvement of deleterious behavioral phenotypes. Systematic testing of potential mechanisms mediating these effects led us to favor a model in which rapamycin induces a metabolic shift in NDUFS4 KO brains toward amino acid catabolism and away from glycolysis, thus alleviating the buildup of glycolytic intermediates. Following this set of discoveries, we expanded our findings to test whether dietary rapamycin delivered at higher doses than previously used could improve lifespan and abnormal weight phenotypes in NDUFS4 KO mice, similar to what was found for high dose injections. Dietary rapamycin doses were tested at 42 ppm, 126 ppm and 378 ppm, corresponding to 3-fold, 9-fold and 27-fold increases from the standard 14 ppm dosage used by the NIH Interventions Testing Program, respectively. As a result of these treatments, NDUFS4 KO lifespan was significantly extended, with successively higher dosages correlating with increased survival. We also found that dietary rapamycin at 126 and 378 ppm had significant effects on body weight and fat mass in male and female wild-type mice. Finally, we conducted a pilot study investigating the effectiveness of high dose rapamycin treatment in treating the Parkinson's disease-like pathology of mice exposed to the toxic drug MPTP. Our results show that rapamycin treatment partially reduced neuron degeneration in the substantia nigra resulting from MPTP exposure, consistent with previous reports. In addition, MPTP mice showed evidence for hyperactive mTOR signaling compared to control mice, which could be potently reduced by rapamycin treatment. No significant changes in body weight or fast mass were found as a result of MPTP exposure, or as a result of an interaction between MPTP and rapamycin. When accounting for different age cohorts, middle aged mice that had been exposed to MPTP performed better on a rotarod task after receiving rapamycin treatment. Our young cohort, however, did not show any differences in performance between treatment groups. Thus, we believe that MPTP induces age-dependent phenotypes that may have been overlooked in previous studies utilizing young mice. Thus far, comparison of these studies suggests that rapamycin treatment has both overlapping and distinct effects that contribute to attenuation of neural pathology of NDUFS4 and MPTP mouse models.

Pathological Pregnancies: The Trump Administration’s Assault on Migrant Women’s Reproductive Health and how Brown Women Activists Spoke Back to Power

de Saint Felix, Skye Cambre University of Maryland, College Park ProQuest Diss 2022 해외박사(DDOD)

Abortion and immigration are two polarizing political issues in the United States. These issues were made more contentious under the Trump administration (2017-2021) that tapped into cultural and historical memories of abortion as a pathological practice. Situated at the intersection of abortion and immigration rights, migrant women’s reproduction was treated as something to be monitored and controlled to preserve white patriarchal interests. The Trump administration capitalized on the racist and sexist tenets inherent to rhetorical pathology to construct an enemy in migrant women that only his administration was qualified to neutralize through deportation, arrest, and extreme legislation. Rhetorical pathology, in the context of anti-abortion and anti-migrant policies, resulted in contradictory commitments. For instance, the Trump administration and his supporters at once humanized the fetus, but dehumanized Brown women and children by blocking them from entering the country and accessing basic needs. Administrative officials also argued that their anti-abortion platform prevented racial genocide by saving Black and Brown babies while they treated them as enemy threats to be purged from the country.I ultimately argue that white supremacy and patriarchy are unifying ideologies in rhetorical pathology that help these contradictions “make sense” for Trump supporters and anti-abortion groups. In Chapter One, I examine the Trump administration’s efforts to force birth and block paths to citizenship for migrant girls by studying the case of Jane Doe and the abuses she faced in the Office of Refugee Resettlement Custody (ORR). In Chapter Two, I investigate how white supremacists and misogynists co-opted progressive rhetoric to undermine its force by analyzing Trump’s policies that heavily regulated migrant women’s reproduction. Such cruel and unconscionable actions included reinstating (and expanding) the Global Gag Rule and passing “conscience” legislation that allows healthcare providers to discriminate against healthcare they deem “immoral” like abortion care or emergency contraceptives. In this chapter, we also see how conservatives inverted progressive frames like “Black Lives Matter” to argue that “Babies Lives Matter” to fulfill an anti-choice agenda and describe themselves as abolitionists and saviors of Brown children.In Chapter Three, I show the ways in which Brown women activists reappropriated the rhetorical power that conservatives mimicked to justify their inhumane policies. Activist women reclaimed their rhetorical power of definition, shared stories of both horror and community uplift, and used rhetorical secrecy to combat rhetorical pathologizations. Legislation in support of migrant women emphasized healing and care to undermine the rhetorics of pathology. This project ultimately exposes how rhetorical pathology operates in order to neutralize its power and center the voices and experiences of migrant women in abortion and immigration debates.

Nitric oxide function in dystrophin-deficient muscular dystrophy

Henricks, Michelle University of California, Los Angeles 2002 해외박사(DDOD)

Duchenne muscular dystrophy is a lethal, inherited disease characterized by progressive muscle wasting. The disease is complex and involves multiple pathogenic mechanisms including an immune response. The primary cause of the disease is mutation of the gene that codes for dystrophin, a protein that is normally found at the muscle cell membrane. Dystrophin is part of a transmembrane complex of proteins that are downregulated in the absence of dystrophin. The nitric oxide (NO)-producing enzyme, neuronal nitric oxide synthase (nNOS), is a member of the downregulated, dystrophin-associated complex, but it is unknown whether its reduction contributes to the dystrophic pathology. I tested whether the reduction of nNOS and NO in dystrophin-deficient skeletal muscle contributes to the pathology of muscular dystrophy by generating a dystrophin-deficient mouse (mdx) in which levels of NO are normalized through expression of a nNOS transgene (nNOS TG). I analyzed characteristics of the disease including central nucleation of fibers, fiber size and variability, and membrane integrity and concluded that mdx/nNOS TG mice have significantly less pathology at the peak of the disease. To determine if the improvement in pathology is due to NO-mediated attenuation of the immune response, I measured the concentration of macrophages, MHC class II+ cells, eosinophils, CD4+ cells, and CD8+ cells. The concentrations of macrophages and MHC class II+ cells are significantly reduced in mdx/nNOS TG muscle. None of the other cells types is affected. Additionally, I observed that a greater percentage of the mononuclear cells in mdx/nNOS TG muscle are apoptotic. I also analyzed whether NO-mediated regulation of myostatin, a negative regulator of muscle mass, contributes to the improved pathology in mdx/nNOS TG mice. The results show that decreased NO in dystrophin-deficient muscle does not cause increases in myostatin concentration and, therefore, suggests that myostatin does not contribute to the dystrophic pathology. These findings suggest that normalizing NO production in mdx mice ameliorates the dystrophic pathology by inducing apoptosis of macrophages. The improvement in pathology persists into adulthood demonstrating that normalizing NO production in dystrophin-deficient tissue truly ameliorates the disease rather than delaying its onset.

Needs Analysis of Genetics and Genomics in Communication Sciences and Disorders: Evidence for Change

LeBlanc, Etoile M Columbia University 2012 해외박사(DDOD)

Purpose: Signaled by the completion of the Human Genome Project in 2003, rapid and escalating discovery in genome science has initiated a paradigm shift in education training and healthcare practices. This shift has required healthcare educators and professionals to possess a level of genetic and genomic literacy and competency. The current study was designed to survey the current state of the perceptions of genetics and genomics in educational and clinical practices within the field speech-language pathology. Method: Seventy-five program directors of degree programs and 265 speech-language pathologists participated in two web-based surveys. Results: Program directors and speech-language pathologist reported to be aware of recent genetic and genomic advancements in speech-language pathology. Ninety-six percent of program directors expected graduated students to demonstrate competency in genetic and genomic related clinical services. Thirty-six percent of program directors reported graduated students were prepared to understand genetics. Seventy-three percent of speech-language pathology programs offered genetic content in their curricula. In comparison, eighty-three percent of speech-language pathologists reported performing genetic related services within their clinical practices. Less than half of respondents reported confidence in performing clinical services. Speech-language pathologists reported minimal to no knowledge of at least 85% of genetic or genomic principles related to speech-language pathology. Sixty-three percent of speech-language pathologists reported their degree-training program had not prepared them to understand genomics in speech-language pathology. Results of a needs index revealed discrepancies between perceptions of speech-language pathologist's performed clinical services and program director's expected competencies, and between level of perceived preparedness and perceived knowledge. Thematic analysis across perceptions, course content, expected competencies, clinical services, and areas of knowledge reflected principles of Mendelian inheritance and single gene disorders. This "medical genetics" perspective is one typically used prior to the completion of Human Genome Project in 2003. Conclusion: The results of this investigative study suggest the field of communication sciences and its disorders is not keeping pace with the demands of new advancements in genetics and genomics. Several discrepancies may contribute to misconceptions and misinformation surrounding genetics and genomic in speech-language pathology. This study provides a foundation for discussion of curriculum reform at the graduate level and policy changes in standard practices of speech-language pathologists at the national level.

Role of astrocytes in the pathogenesis of tauopathies

Dabir, Deepa V University of Pennsylvania 2006 해외박사(DDOD)

Filamentous tau inclusions in neurons, astrocytes and oligodendrocytes are the neuropathological hallmark of both sporadic and familial tauopathies. The identification of pathogenic tau mutations in familial tsuopathies, termed frontotemporal dementia with parkinsonism linked to chromosome-17, provide unequivocal support for the hypothesis that defects in the tau gene are sufficient alone to cause neurodegeneration. While the role of deposition of filamentous tau aggregates in neurons as well as neuron loss in the neurodegenerative process is largely accepted, the relative contribution of the glial pathology is mostly unknown. The purpose of the studies presented in this dissertation is to better understand the role of astrocytic tau pathology in neuronal dysfunction and consequential development of neurodegeneration. First, we examined the role of heat shock proteins (HSPs) to disease pathogenesis of tauopathies with abundant glial pathology. We demonstrate increased expression of the small HSP, alphaB-crystallin specifically in glial tau inclusions of both sporadic and familial tauopathies suggesting a specific response by glia to the accumulation of misfolded protein. Secondly, to better understand the functional contribution of astrocytic tau pathology to disease pathogenesis, we developed the first transgenic mouse model of tau expression restricted to astrocytes. These Tg mice manifest an age-dependent accumulation of tau pathology in astrocytes similar to the human disease. We also demonstrate functional consequences of this pathology including reduced expression and activity of the filial glutamate transporters, GLT-1 and GLAST that correlated with compromised motor function. Thus, the GFAP/tau Tg mice suggest a role for altered astrocyte function in disease pathogenesis. Lastly, we generated mixed astrocyte/neuron cultures from the GFAP/tau Tg mice to assess the consequences of astrocytic tau expression on neuron survival. In mixed cultures generated from GFAP/tau Tg mice, we demonstrate reduced neuron survival that was blocked by NMDA receptor antagonists indicative of glutamate-mediated excitotoxicity. In conclusion, these studies propose that distinct mechanisms underlie the pathogenesis of glial versus neuronal tau pathology in tauopathies. It provides a better understanding of the significance of astrocytic tau pathology to the process of neurodegeneration. More importantly, they elucidate novel pathways that contribute to the disease pathogenesis of tauopathies.

Genetic and epidemiologic assessment of Schistosoma haematobium induce kidney and bladder pathology in rural Zimbabwe

Brouwer, Kimberly Christa The Johns Hopkins University 2001 해외박사(DDOD)

Disease outcome in persons infected with <italic>Schistosoma haematobium </italic> can vary dramatically, ranging from mild symptoms to severe damage of the kidneys and/or bladder. This study explores the relationship of a number of epidemiological, parasitological, and genetic parameters with urinary tract pathology in children from rural Zimbabwe. We surveyed 551 primary school students (9–16 years old) from three schools in the Chikwaka Communal Lands for schistosomiasis; of these, 59.7% were infected with <italic>Schistosoma haematobium</italic>. Ultrasound examinations of urinary tract organs were performed on 221 of the students. Kidney and bladder pathology were significantly linked to current <italic>S. haematobium </italic> infection status (<italic>P</italic> = 0.04 and <italic>P</italic> < 0.001 respectively). Among those infected, 49.7% had bladder damage and 33.7% had dilation of the pyelon of at least one of their kidneys. In order to characterize the nature of transmission in the area and compare epidemiological parameters with morbidity, 247 of the students were administered a questionnaire concerning water exposure and other activities. Intensity of infection, certain water contact behaviors, and male gender were associated with bladder damage, with disease intensity accounting for most of the pathology. Kidney pathology was more prevalent in students from the schools closest to the major rivers in the area. No other parasitological or demographic characteristics were associated with kidney damage. For 25 students, 12 with mild and 13 with severe infections, additional urine specimens were taken to enable characterization of the parasite genotypes composing their infections. By performing monomiracidial infections of host snails to replicate the parasite, we were able to obtain sufficient quantities of parasite DNA while minimizing the selection normally seen during passaging of the parasite through a rodent host. Using four RAPD primers on each of 133 miracidial isolates, allelic frequencies at 53 loci were scored. Mean heterozygosity of the population was 0.116 ± .043. Analysis of molecular variance revealed that parasite diversity was high within hosts but comparatively low between hosts. Using a cluster analysis, 13 parasite families were found to circulate in the area, with the occurrence of three significantly linked to pathology. Our work suggests that intensity of infection and the presence of particular parasite strains may influence disease outcome with urinary schistosomiasis. The high level of <italic>S. haematobium</italic> diversity within persons reflects the chronic nature of exposure to the parasite, while low interhost diversity suggests panmixia. To improve understanding of risk factors for kidney pathology, it may be necessary to conduct long term studies which take into account the pattern of parasite exposure. Further characterization of the parasite families that were linked with more severe disease outcome may reveal a possible genetic mechanism for parasite virulence.