160 research outputs found
Leigh Syndrome: Subgroup Aanalysis according to Mitochondrial DNA Mutation
Purpose: Leigh syndrome (LS) is a rare, progressive neurodegenerative disorder with characteristic abnormalities in the central nervous system. Such patients present with heterogeneous clinical symptoms and genetic abnormalities; thus, prognosis is difficult to anticipate. The present study investigates whether distinct patient characteristics are associated with mitochondrial DNA (mtDNA) mutation in LS patients. Methods: : We retrospectively analyzed data from patients diagnosed with LS at our hospital who were assessed using genomic sequencing of mtDNA. A subgroup analysis was performed to divide patients according to the mtDNA sequencing results. Results: Among the 85 patients enrolled, 18 had mtDNA mutations. Most patients had lactic acidosis and a lactate/pyruvate ratio above 20, indicating respiratory chain abnormalities. In the subgroup analysis, the mutation group had a significantly higher female-to-male ratio, alanine level, ocular involvement, and midbrain and medulla abnormalities on magnetic resonance imaging (MRI). Conclusion: The subgroup analysis indicates that mtDNA sequencing is recommended for female patients, or those who exhibit ocular involvement, high alanine levels, or MRI findings with lesions in the midbrain and medulla.ope
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Όλ¬Έ(μμ¬) -- μμΈλνκ΅λνμ : μ¬λ²λν κ΅μ‘νκ³Ό(κ΅μ‘νμ 곡), 2021.8. μ μ±μ.This study aims to identify the process in which students who are maladjusted at school, maintain their school lives through βan alternative classroom in school,β and to see how teachers perceive the school-adjustment process and make it meaningful. The study started with raising a question of whether it is fair to distinguish between students who are non-maladjusted and maladjusted according to the standards prescribed by society and schools and to ask for change from individuals who are maladjusted. To solve this problem, this study conducted interview-driven qualitative research on teachers in charge of alternative classrooms by selecting the cases that are operated separately from ordinary classes for students who are maladjusted at schools. The results of this study are summarized as follows. The teachers perceived the purpose of alternative classrooms as βfor graduationβ, βfor maintenance of school lifeβ and βproviding alternative educational opportunities.β Also, they viewed the characteristics of students who fail to adjust themselves to alternative classrooms as causing problems that are apparently noticeable, refusing classes, and being silent because they do not fit the school system. Students who exhibit these maladjustment characteristics are found mainly through the teacherβs continuous observation. Furthermore, a process of persuading those students to participate in an alternative classroom operates, when it is judged that they need help. Alternative classroom activities are encouraged by teachers to give options to participating students who are maladjusted and find activities that they want to do independently rather than pre-determined. The alternative classroom consists of a variety of subject-oriented activities in a free and flexible manner. Meanwhile, school membersβ perceptions of alternative classrooms and students where are maladjusted were mostly negative. The purpose and operation of these alternative classes served as a βschool life maintenance systemβ for students who were maladjusted at school. The teachers perceived the main changes in students who were maladjusted through alternative classes as adjustmentβ and βmaintenanceβ of school life. In other words, this can be seen as βan improved attitude in classβ before participating in alternative classes or βa change in maintaining school life without leaving school.β However, it was followed by opinions that such changes in students who were maladjusted are only seen for a while, and thus, the fundamental problem of maladaptation could not be seen as gone. That is, the existing schools and classrooms where students lived are still the same, and the environment that was inappropriate has not changed, so the phenomenon of maladjustment can reappear at any time. The reason why alternative classes can only serve as a temporary school life maintenance system for students who are maladjusted at school was because it was the limitations of the standardized curriculum and assessment system as well as the expected student image in class. Furthermore, the expected student image in class which sustains such a reproduction structure, allows maladjusted students to be marginalized in school. Alternative classes were intended to provide βAlternative Education in Public Educationβ opportunities for students who are maladjusted at school, but behind this, they were operated mainly for the prevention of academic interruptions through national intervention. In addition, through the ambiguous distinction between non-alternative classes and alternative classes, the method of βinclusive controlβ was chosen, rather than complete isolation of students who are maladjusted. Using the marginalized (separated) space and time of alternative classrooms, the scope of school adjustment standards and school education is expanded, and thus it looks like that the previously maladjusted individuals have changed and coexist in schools together. As such, maladjusted students were clearly recognized in school in the past, and today it seems that they coexist together, but as this study confirmed, they remain maladjusted and are becoming ambiguously marginalized.λ³Έ μ°κ΅¬λ νκ΅λΆμ μ νμμ΄ βνκ΅ λ΄ λμκ΅μ€βμ ν΅ν΄ νκ΅μνμ μ§μνλ κ³Όμ μ νμ
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μ μ κ²½μ§μ±νλ°μ λ§λΉ λ¨λ°±μ§μΈ Spartinμ μν μλ μ€ μ±μ₯κ³Ό μ κ²½μΈν¬ μμ‘΄μ μ‘°μ
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μ€ μ λ§λ¨μ μ‘΄μ¬νλ BMP μμ©μ²΄μΈ Wishful Thinking (Wit)μ endocytic degradationμ μ λνμ¬ BMP μ νΈμ λ¬μ μ΅μ ν¨μΌλ‘μ¨ μλ
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νμλ€. νΉν spartin λμ°λ³μ΄μμ κ΄μ°°λ μλ
μ€μ κ³Ό μ±μ₯κ³Ό μ±μ²΄ λμ neurodegenerationμ μν μ΄μμ λ―ΈμΈμκ΄μ μμ μ±μ μ ν΄νλ μ½λ¬ΌμΈ Vinblastine (VB)μ μν΄ λͺ¨λ ν볡λ¨μ κ΄μ°°νμλ€. Spartinμ΄ BMP-dFMRP-Futsch μ νΈμ λ¬μ μ΅μ νμ¬ λ―ΈμΈμκ΄ μμ μ±μ μ‘°μ νλ©°, μ΄λ₯Ό ν΅ν΄ μλ
μ€ μ±μ₯κ³Ό μ κ²½ μΈν¬ μ¬λ©Έμ μ΅μ ν¨λ₯Ό λ°ν λ³Έ μ°κ΅¬λ λ―ΈμΈμκ΄μ λΉμ μμ μΈ μμ μ± μ‘°μ μ΄ Troyer μ¦νκ΅°μ΄ μ λ°λλ ν΅μ¬κΈ°μ μμ μ μνλ€.Troyer syndrome is a hereditary spastic paraplegia caused by human spartin (SPG20) gene mutations. I have generated a Drosophila disease model showing that Spartin functions presynaptically with endocytic adaptor Eps15 to regulate synaptic growth and function. Spartin inhibits bone morphogenetic protein (BMP) signaling by promoting endocytic degradation of BMP receptor Wishful Thinking (Wit). Drosophila Fragile X Mental Retardation Protein (dFMRP) and Futsch/MAP1B are downstream effectors of Spartin and BMP signaling in regulating microtubule stability and synaptic growth. Loss of Spartin or elevation of BMP signaling induces age-dependent progressive defects resembling hereditary spastic paraplegias, including motor dysfunction and brain neurodegeneration. Null spartin phenotypes are prevented by administration of the microtubule-destabilizing drug vinblastine. Together, these results demonstrate that Spartin regulates both synaptic development and neuronal survival by controlling microtubule stability via the BMP-FMRP-Futsch pathway, suggesting that impaired regulation of microtubule stability is a core pathogenic component in Troyer syndrome.CONTENTS
ABSTRACT
CONTENTS
LIST OF FIGURES
ABREVIATIONS
I. Introduction
1. Retrograde Bone Morphogenetic Protein (BMP) Signaling in Synapse Development
2. Troyer Syndrome, Is an Autosomal Recessive Form of Hereditary Spastic Paraplegia that Is Caused by Loss-of-Function Mutations in the spartin Gene (SPG20)
3. The Drosophila Neuromuscular Junction (NMJ) and Adult Brain
4. Rationale and Outline of the Thesis Experiments
II. Materials and Methods
1. Drosophila Stocks and Transgenes
2. Molecular Biology
3. Cell Culture and Double-Stranded RNA Interference
4. Generation of Anti-Spartin Antibody and Western Blot Analysis
5. Immunohistochemistry and Imaging of Larval NMJs
6. Electrophysiology and FM1-43 Uptake Assays
7. Histology, Immunostaining, and TUNEL Staining of Adult Brains
8. Adult Behavioral Analysis
9. Statistical Analysis
III. Results
1. Generation of spartin Null Mutant
2. Spartin Is Localized Presynaptically at the NMJ
3. Spartin Is Required Presynaptically for Normal Synaptic Growth
4. Spartin Is Required Presynaptically for NMJ Neurotransmission
5. Spartin Interacts with Eps15 to Regulate Synaptic Growth and Synaptic Endocytosis
6. Spartin Inhibits BMP Signaling by Endocytic Downregulation of the Type II BMP Receptor Wit
7. Spartin Regulates Synaptic Growth by Modulating Microtubule Stability through Futsch
8. Spartin and BMP Signaling Regulate the Expression of dFMR1, a Negative Regulator of Futsch
9. Loss of spartin Function in Neurons Causes Movement Defects and Progressive Neurodegeneration
10. Spartin/BMP-Mediated Regulation of Microtubule Stability Is Critical for Neuronal Survival
IV. Discussion
V. References
ABSTRACT IN KOREANDocto
Interactions between Shh, Sostdc1 and Wnt signaling and a new feedback loop for spatial patterning of the teeth
Each vertebrate species displays specific tooth patterns in each quadrant of the jaw: the mouse has one incisor and three molars, which develop at precise locations and at different times. The reason why multiple teeth form in the jaw of vertebrates and the way in which they develop separately from each other have been extensively studied, but the genetic mechanism governing the spatial patterning of teeth still remains to be elucidated. Sonic hedgehog (Shh) is one of the key signaling molecules involved in the spatial patterning of teeth and other ectodermal organs such as hair, vibrissae and feathers. Sostdc1, a secreted inhibitor of the Wnt and Bmp pathways, also regulates the spatial patterning of teeth and hair. Here, by utilizing maternal transfer of 5E1 (an anti-Shh antibody) to mouse embryos through the placenta, we show that Sostdc1 is downstream of Shh signaling and suggest a Wnt-Shh-Sostdc1 negative feedback loop as a pivotal mechanism controlling the spatial patterning of teeth. Furthermore, we propose a new reaction-diffusion model in which Wnt, Shh and Sostdc1 act as the activator, mediator and inhibitor, respectively, and confirm that such interactions can generate the tooth pattern of a wild-type mouse and can explain the various tooth patterns produced experimentally.ope
Comparison of Postoperative Gastrointestinal Motility of Sugammadex and Neostigmine in Patients Undergoing Robotic Thyroidectomy: A Retrospective Study
Postoperative bowel dysfunction poses difficulty to patients during their recovery from surgery, and reversal agents may affect bowel function. This study aimed to investigate and compare the effects of sugammadex and a neostigmine/glycopyrrolate combination on postoperative bowel movement in patients undergoing robotic thyroidectomy. The electronic medical records of 122 patients, who underwent robotic thyroidectomy between March 2018 and December 2020, were retrospectively reviewed. Demographic, clinical, and laboratory findings and the first gas-passing time after surgery were assessed. The number of patients with a first gas emission time over 24 h was significantly higher in the neostigmine group than in the sugammadex group (p = 0.008). Multivariate logistic regression analysis indicated that sugammadex was a prognostic factor for the first gas-passing time within 24 h (odds ratio = 4.60, 95% confidence interval 1.47-14.36, p = 0.005). Although postoperative bowel motility, based on the first gas emission time, was comparable, the number of patients with a first gas emission time within 24 h was significantly higher in the sugammadex group than in the neostigmine group. This shows that the use of sugammadex did not affect the delayed recovery of postoperative bowel motility after robotic thyroidectomy.ope
Effects of hyaluronan on carrageenan-induced synovitis in rat TMJ
Nitric oxide is one of many proinflammatory mediators that are involved in temporomandibular joint (TMJ) inflammatory disorder and is synthesized by inducible nitric oxide synthase (iNOS). iNOS is transcriptionally regulated by nuclear factor-kappaB (NF-kappaB) in cases of inflammation, proliferation, and apoptosis. It has also been reported that nitric oxide is positively regulated by carrageenan and negatively regulated by hyaluronan in the knee joint. The aim of this study was to histologically evaluate how inflammation and cell proliferation of the synovial membrane are affected by the exogenous administration of carrageenan and hyaluronan in the rat TMJ by investigating iNOS, NF-kappaB, and anti proliferating cell nuclear antigen (PCNA) immunoreactivity. As results, immunoreactive cells to iNOS, NF-kappaB, and PCNA were normally localized only in the synovial membrane of wild type TMJs. The numbers of immunoreactive cells were extensively larger in the carrageenan-injected synovial membranes exhibiting excessive folding, and smaller in the hyaluronan-injected synovial membranes showing a few folds. These results indicate that a carrageenan injection induced inflammation and cell proliferation especially in the synovial membrane and that hyaluronan relieved the inflammation by decreasing inflammatory molecules in the synovial membrane.ope
Green Urine after Propofol Infusion in the Intensive Care Unit
Urine discoloration occurs in the intensive care unit (ICU) due to many causes such as medications, metabolic disorders, and infections. Propofol is advocated as one of the first line sedatives in the ICU, but it is not well known to the intensivists that propofol can induce urine color change. We experienced two cases of green urine after propofol infusion. Propofol should be warranted as the cause of urine discoloration during ICU stay.ope
Ihh and Runx2/Runx3 signaling interact to coordinate early chondrogenesis: a mouse model
Endochondral bone formation begins with the development of a cartilage intermediate that is subsequently replaced by calcified bone. The mechanisms occurring during early chondrogenesis that control both mesenchymal cell differentiation into chondrocytes and cell proliferation are not clearly understood in vertebrates. Indian hedgehog (Ihh), one of the hedgehog signaling molecules, is known to control both the hypertrophy of chondrocytes and bone replacement; these processes are particularly important in postnatal endochondral bone formation rather than in early chondrogenesis. In this study, we utilized the maternal transfer of 5E1 to E12.5 in mouse embryos, a process that leads to an attenuation of Ihh activity. As a result, mouse limb bud chondrogenesis was inhibited, and an exogenous recombinant IHH protein enhanced the proliferation and differentiation of mesenchymal cells. Analysis of the genetic relationships in the limb buds suggested a more extensive role for Ihh and Runx genes in early chondrogenesis. The transfer of 5E1 decreased the expression of Runx2 and Runx3, whereas an exogenous recombinant IHH protein increased Runx2 and Runx3 expression. Moreover, a transcription factor Gli1 in hedgehog pathway enhances the direct induction of both Runx2 and Runx3 transcription. These findings suggested that Ihh signaling plays an important role in chondrocyte proliferation and differentiation via interactions with Runx2 and Runx3ope
An Immune-compromised Method for Tooth Transplantation Using Adult Bone Marrow Stromal Cells and Embryonic Tooth Germ
Tooth transplantation using autogenic adult teeth or embryonic tooth germs is the one of best treatments for replacement of missing teeth, but there are limitations in the accessibility. Isogenic or xenogenic tooth transplantation has been failed because of the immune rejection response occurring in the periodontal ligament of transplanted tooth. In this study, by utilizing the recombination between mouse embryonic tooth germ and mouse adult bone marrow stromal cells, we tried to replace the periodontal tissues such as periodontal ligament and alveolar bone with adult bone marrow stromal cells. At four weeks after the transplantation of the recombinant into a kidney, adult bone marrow-derived cells cells were observed in the periodontal ligament and alveolar bone. This result indicates that adult bone marrow stromal cells can participate in the formation of periodontal tissues. If these tooth and periodontal tissues are transplanted into host who donates adult bone marrow stromal cells, adult bone marrow-derived cells will be regarded as host cells, and immune rejection response will not occur in these cells. Therefore, it is suggested that recombination between adult bone marrow stromal cells and embryonic tooth germ is a good candidate method using xenogenic tooth germ for replacement of missing teeth in human by replacing cells in periodontal tissues with human adult bone marrow stromal cells.ope
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