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Respiratory function as a measure of muscle strength in young boys with Duchenne muscular dystrophy /Webster, Richard Ian. January 2003 (has links)
Thesis (M. Sc.)--University of New South Wales, 2003. / Also available online.
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Crosstalk Between the Planar Cell Polarity and Hedgehog Signaling Pathways Influences Satellite Cell FateFreeman, Emily 16 January 2019 (has links)
Our laboratory has identified two secreted proteins, Wnt7a and Sonic hedgehog (Shh), that regulate satellite cell (SC) fate, during muscle differentiation. While Wnt7a stimulates symmetric SC division through the planar cell polarity (PCP) pathway, Shh activates Myf5 expression in the committed SC following asymmetric division through cilia-mediated Hedgehog (Hh) signaling. Crosstalk between these pathways has been well characterized during development, and is likely to be conserved in muscle regeneration. Indeed, accumulating evidence suggests the PCP pathway influences primary cilia formation, an organelle required for proper Hh signal transduction. Here we show that Wnt7a treatment in primary myoblasts increases the presence of primary cilia. Additionally, using myofiber culture, we demonstrate that Wnt7a increases myogenin (MyoG) expression. Removal of primary cilia through a small interfering RNA (siRNA) targeted towards IFT88 impedes Wnt7a mediated MyoG expression, suggesting crosstalk between the PCP and Hh pathways facilitates muscle differentiation. Furthermore, through siRNA knockdown we have identified the downstream PCP effectors, Inturned and Fuzzy as the main candidates responsible for this crosstalk. Knockdown of either Inturned or Fuzzy impedes Wnt7a-mediated MyoG expression. Taken together our data demonstrates crosstalk between the PCP pathway and Hh signaling regulates the differentiation of SCs.
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Efeito do uso da ankle-foot orthosis na biomecânica da marcha de pacientes com Distrofia Muscular de Duchenne / Effect of use of ankle-foot orthosis on the gait biomechanics of patients with Duchenne muscular dystrophyMariana Angélica de Souza 05 December 2014 (has links)
O objetivo deste estudo foi avaliar o efeito do uso noturno ou diurno da ankle-foot orthosis (AFO) na biomecânica da marcha de pacientes com DMD. Foram avaliados 20 pacientes deambuladores, do Ambulatório de Miopatias Infantis do CER do HCFMRP-USP, com diagnóstico de distrofia muscular de Duchenne (DMD), com idades entre 4 e 12 anos. Foi realizada a avaliação inicial (Av1) em todos os pacientes e, 7 pacientes foram reavaliados após 6 meses (Av2). Na Av1, os pacientes foram agrupados conforme o uso da órtese: grupo sem órtese (SO; n=7), grupo órtese noturna (ON; n=7), grupo órtese diurna (OD; n=6). Na Av1 e na Av2 foram obtidos dados de massa corporal, altura, composição corporal pela bioimpedância elétrica, escore funcional pela escala medida da função motora, amplitude passiva de movimento articular, força muscular isométrica pelo dinamômetro Handheld e avaliação biomecânica da marcha, na velocidade habitual do paciente. Os pacientes que faziam uso da órtese diurna foram avaliados sem e com órtese, sendo denominados grupos ODs e ODc, respectivamente. Os dados foram analisados de três formas: duas transversais e uma longitudinal. Nas análises transversais, foram realizados dois procedimentos: (i) comparando dados dos grupos SO x ON x ODs; (ii) comparando dados dos grupos SO x ON x ODc. Nestas, foi utilizado o teste ANOVA, considerando um nível de significância de 5%. Na análise longitudinal, foi realizada a análise descritiva comparando os dados obtidos na Av1 e Av2, individualmente para os 7 pacientes reavaliados. Transversalmente, o grupo ODc apresentou maiores picos do ângulo de dorsiflexão e do momento dorsiflexor, menor ângulo de flexão plantar e menor geração de potência de tornozelo (p<0,05) que o grupo SO. Porém, ao caminhar sem a AFO (grupo ODs) estes resultados não foram observados (p>0,05). Em relação ao grupo ON, o grupo ODc obteve menores picos do ângulo de flexão do quadril, de absorção de potência de quadril, do ângulo de flexão plantar e maior pico do momento dorsiflexor (p<0,05), sendo que ao retirar a AFO (ODs) essas diferenças não foram observadas (p>0,05). E ainda, o grupo ON obteve maior pico do ângulo de flexão do joelho e menor momento flexor de quadril (p<0,05) em relação ao grupo ON. Na comparação dos dados entre os grupos SO e ON, o grupo ON obteve maior pico do ângulo de flexão do joelho e maior absorção de potência de quadril (p<0,05). Na análise longitudinal individual foi observado que os 2 pacientes que iniciaram precocemente e mantiveram o uso noturno da AFO apresentaram na Av2 maior velocidade da marcha, maiores momentos extensor de quadril e flexor plantar e maior geração de potência de tornozelo, contrariamente aos paciente que interromperam o uso (noturno ou diurno) da AFO. Conclui-se que o uso diurno da AFO acarretou alterações positivas na biomecânica da marcha, minimizando compensações típicas da DMD na articulação do tornozelo. O uso noturno da AFO, quando iniciado precocemente, também afetou positivamente a marcha dos pacientes. Assim, sugere-se o início precoce e contínuo do uso diurno e noturno da AFO aos pacientes com DMD. / The aim of this study was to evaluate the effect of the ankle-foot orthosis (AFO) during nocturnal or daytime usage of the gait biomechanics in patients with Duchenne Muscular Dystrophy (DMD). Twenty ambulant patients from the Myopathies Infant Ambulatory of CER - HCFMRP-USP, were diagnosed with DMD between the ages of 4 and13 years and were evaluated. The initial evaluation (Ev1) was performed in all patients, and 7 patients were reevaluated after 6 months (Ev2). In Av1, patients were grouped according to orthosis use: group without orthosis (NoO, n = 7), group with nocturnal orthosis (NiO, n = 7), group with daytime orthosis (DO, n = 6). In Ev1 and Ev2 data were obtained according to the weight, height, body composition (bioelectrical impedance), functional score (Measure scale of motor function), passive joint range of motion, isometric muscle strength (dynamometer Handheld) and biomechanical gait analyses (usual velocity for the patient). Patients who used the daytime orthosis were evaluated with and without bracing, respectively. The data were analyzed in three ways; the first two were cross-sectional and the other one was longitudinal. In the cross-sectional analyzes, an exploratory analysis of the data from each evaluation was performed, and subsequently, the variables were compared between groups, considering the means and standard deviations. ANOVA test was used, and it was considered a significant level of 5%. In the longitudinal analysis, the description of the data obtained in the evaluation 1 compared to the data obtained in the evaluation 2 was individually performed in the 7 patients who were reevaluated. A cross-sectional analysis compared the data between NoO x NiO x DO groups considering the gait analysis data from the DO group without the orthosis (barefoot), being named DOno. The other cross-sectional analysis compared the data between NoO x NiO x DO groups considering the gait analysis data from the OD group with orthosis, being named DOwith. In individual longitudinal analysis, it was observed that patients who had started early and kept the nocturnal usage of AFO which has been already showed, in six months, an increment of gait velocity, hip extensor and plantar flexor moments and also the increment of ankle power generation, which is the opposite of the patient who has discontinued the AFO usage (daytime or nocturnal). In the cross-sectional analyzes it was observed that, compared to the NoO group, the DOwith group had a higher dorsiflexion angle peak and higher dorsiflexor moment peak (p<0.05). However, when they walked without the device these results were not maintained. There was no difference (p>0.05) between DOno and NoO groups for the kinematic parameters. And, the DOno group had lower plantar flexor moment maximum peak than the SO group (p>0.05). It was concluded that AFO daytime use cause positive changes in gait biomechanics, minimizing typical compensation of DMD in the ankle joint. The night use of AFO, when started early, also positively affected the gait of patients. Thus, it is suggested early prescription of daytime and nocturnal usage of AFO for DMD patients.
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Becoming a back-up carer: parenting sons with Duchenne Muscular Dystrophy transitioning into adulthood / バックアップケア提供者となること―成人移行期のデュシャンヌ型筋ジストロフィー患者への親の関わりYamaguchi, Miku 23 March 2015 (has links)
京都大学 / 0048 / 新制・課程博士 / 博士(人間健康科学) / 甲第18910号 / 人健博第24号 / 新制||人健||2(附属図書館) / 31861 / 京都大学大学院医学研究科人間健康科学系専攻 / (主査)教授 十一 元三, 教授 我部山 キヨ子, 教授 平家 俊男 / 学位規則第4条第1項該当 / Doctor of Human Health Sciences / Kyoto University / DFAM
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The Impact of Oral Bisphosphonate Therapy on Vertebral Morphometry in Patients with Duchenne Muscular Dystrophy and Glucocorticoid-Induced OsteoporosisNasomyont, Nat 15 June 2020 (has links)
No description available.
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Effects of Lipin1 Deficiency & Restoration in the Dystrophic DiaphragmBrown, Alexandra 23 May 2022 (has links)
No description available.
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Treatment of DMD 5’ Mutations through Two Different Exon 2 Skipping Strategies: rAAV9.U7snRNA Mediated Skipping and Antisense Morpholino OligomersSimmons, Tabatha Renee 22 December 2016 (has links)
No description available.
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Dynamic Regulation of Cardiac Contractility & Cardiomyopathy in Duchenne Muscular DystrophyXu, Ying 25 July 2011 (has links)
No description available.
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Physiological adaptations in mdx mice treated with microdystrophin gene therapy and endurance exerciseHamm, Shelby Elizabeth 08 June 2022 (has links)
Duchenne muscular dystrophy (DMD) is a fatal, x-linked disease that causes progressive muscle weakness and susceptibility to damage. DMD is caused by a lack of dystrophin, a large muscle protein that performs both structural and signaling functions. A promising treatment currently in clinical trials is microdystrophin gene therapy, which delivers a truncated version of dystrophin to muscle via a viral vector. Preclinical studies have established efficacy of microdystrophin to improve muscle quality and function. With clinical success of this treatment, patients affected by DMD could become more physically active. However, the effect of exercise on both dystrophic and gene therapy-treated muscles is unclear. Recently, we demonstrated that microdystrophin gene therapy with and without 21 weeks of voluntary wheel running (VWR) improved treadmill time to fatigue and in vivo plantarflexor torque output in young mdx mice, a mouse model of DMD. Although treated mice could run well, diaphragm force and power output were blunted by VWR. A subsequent study tested longevity of two different microdystrophin gene therapy constructs in combination with VWR. Versions of each construct are being tested in clinical trials. Construct 1 contained the nNOS-binding site found in full-length dystrophin, which localizes nNOS to the sarcolemma and reduces functional ischemia of exercising limb muscles, while construct 2 lacked the nNOS-binding site and was the same microdystrophin used in the previous study. Gene- therapy treated mice that were sedentary or performed 52 weeks of VWR demonstrated similar outcomes including increased plantarflexor torque and exceptional treadmill endurance capacity. However, ex vivo diaphragm and soleus force, as well as metabolic enzyme and mitochondrial respiration assays were differentially improved, revealing unique physiological adaptations to each microdystrophin construct. Together, the data demonstrated that response to exercise after gene therapy treatment was variable and dependent on age, microdystrophin construct, and muscle type. / Doctor of Philosophy / Duchenne muscular dystrophy (DMD) is a rare, fatal muscle disease that causes progressive muscle weakness and cardiorespiratory failure. Available treatments, such as corticosteroids, slow progression of the disease but do not address the underlying genetic cause. DMD is caused by a genetic mutation that results in the loss of the muscle protein dystrophin. Microdystrophin gene therapy aims to address the genetic cause of the disease by using a non-pathogenic virus to deliver microdystrophin, a small, functional version of dystrophin, to muscle. This gene therapy is in clinical trials, and, if it is successful, treated patients will likely want to engage in more physical activity than previously possible due to muscle weakness. However, the effects of physical activity on muscles treated with gene therapy are unclear. Therefore, we conducted two studies to test the effects of voluntary wheel running on microdystrophin gene therapy in the mdx mouse, a model of DMD. The first study demonstrated that voluntary wheel running was beneficial to whole-body muscle function in mice treated with microdystrophin gene therapy. However, adaptations to the gene therapy and voluntary wheel running were variable in individual muscles. In the second study, we tested two microdystrophin constructs, which each contain different structural components of full-length dystrophin. In addition, mice ran for 52 weeks, more than twice as long as the first study. The results of the second study found that adaptations in individual muscles depended on microdystrophin construct and activity level. Additionally, we confirmed that voluntary wheel running was beneficial to whole-body function of microdystrophin–treated muscles. Together, these studies demonstrated that adaptations of gene therapy-treated muscles were dependent on microdystrophin structure, activity level, and age.
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Immune Response Markers are Prevalent in the mRNA Expression Profile of Maturing Dystrophic Murine Skeletal MuscleGainer, Thomas Gregory 07 June 2005 (has links)
Duchenne muscular dystrophy (DMD) is a severe and fatal muscle wasting disease characterized by a high mutation rate in the gene that encodes the membrane-associated protein dystrophin that results in absence of expressed protein. Although the primary genetic defect for DMD is known, the mechanisms that initiate the onset of DMD are not currently understood. This study tested the hypothesis that pathophysiological processes involved in DMD could be identified by the global expression of mRNA in maturing dystrophin- and utrophin-deficient mouse (mdx:utrn-/-) muscles. Two potential dystrophic onset mechanisms targeted for analysis were (1) disrupted expression of calcium handling proteins; and, (2) increased expression of immune response markers.
An mRNA expression profile was developed following isolation of total RNA from control and mdx:utrn-/- triceps surae (TS) muscles at ages 9-10 and 20-21 days using Affymetrix® Mu74Av2 GeneChips®. Compared to control, the mRNA expression profile in mdx:utrn-/- muscles revealed there was a 3-fold increase in the number of gene transcripts differentially expressed more than 2-fold (53 transcripts at ages 9-10 days; 153 at ages 20-21 days). However, there were no changes in the mRNA transcripts for calcium handling proteins. In distinct contrast, there was up-regulation of transcripts that corresponded to an immune response (40 transcripts), extracellular matrix activity (14), and proteolysis (8). Up-regulation of several transcripts corresponded to cytokines and their receptors (11), chemokines and their receptors (5), and lymphoid and myeloid markers (16) suggesting that dystrophic muscle is susceptible to invasion by macrophages, leukocytes, B- and T-cells. These results are consistent with several reports (Spencer et al., 1997; Chen et al., 2000; Porter et al., 2002; Porter et al., 2003a; Porter et al., 2003b; Porter et al., 2004) that indicate the immune system may play an important role in the early pathophysiology of DMD. Understanding the functional aspects of an immune response in DMD onset should lead to more effective therapeutics. / Master of Science
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