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81.
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Folker JE Murdoch BE Cahill LM Delatycki MB Corben LA Vogel AP 《Clinical linguistics & phonetics》2011,25(1):66-79
Articulatory kinematics were investigated using electromagnetic articulography (EMA) in four dysarthric speakers with Friedreich's ataxia (FRDA). Specifically, tongue-tip and tongue-back movements were recorded by the AG-200 EMA system during production of the consonants /t/ and /k/ as produced within a sentence utterance and during a rapid syllable repetition task. The results obtained for each of the participants with FRDA were individually compared to those obtained by a control group (n = 10). Results revealed significantly greater movement durations and increased articulatory distances, most predominantly during the approach phase of consonant production. A task difference was observed with lingual kinematics more disturbed during the syllable repetition task than during the sentence utterance. Despite expectations of slowed articulatory movements in FRDA dysarthria, the EMA data indicated that the observed prolongation of consonant phase durations was generally associated with greater articulatory distances, rather than slowed movement execution. 相似文献
83.
Corben LA Georgiou-Karistianis N Fahey MC Storey E Churchyard A Horne M Bradshaw JL Delatycki MB 《Brain research bulletin》2006,70(3):197-202
There is limited documentation regarding cognitive function in individuals with Friedreich ataxia (FRDA), possibly because FRDA is widely held to predominantly affect the spinal cord, peripheral sensory nerves and cerebellum and not to affect cognition. Traditionally, the cerebellum has been thought to coordinate voluntary movement and motor tone, posture and gait. However, recent studies have implicated the cerebellum in a range of cognitive functions including executive function, visuospatial organisation and memory. We review the available data on cognitive function and neuroimaging in FRDA and the role of the cerebellum in cognitive function. We conclude with recommendations for future research including correlating cognitive function in individuals with FRDA with possible determinants of disease severity, such as age of onset and the causative genetic mutation. 相似文献
84.
Fahey MC Corben L Collins V Churchyard AJ Delatycki MB 《Journal of neurology, neurosurgery, and psychiatry》2007,78(4):411-413
Background
Friedreich''s ataxia (FRDA), the most common genetic cause of ataxia, is characterised by progressive neurodegeneration and cardiomyopathy. Initial treatments are likely to slow progression rather than reverse morbidity. An appropriate and sensitive scale to measure disease progress is critical to detect the benefit of treatments.Objective
To compare the Friedreich Ataxia Rating Scale (FARS) with other scales proposed as outcome measures for FRDA.Methods
76 participants were assessed with the FARS and the International Cooperative Ataxia Rating Scale (ICARS) and 72 of these participants were also assessed with the Functional Independence Measure and the Modified Barthel Index. 43 participants had repeat measures at an interval of 12 months. Sensitivity and responsiveness were assessed using the effect size for each measure and the sample size required for a placebo‐controlled clinical trial.Results
The FARS showed a high correlation with the other three measures. A significant change in the score over 12 months was detected by the FARS, the International Cooperative Ataxia Rating Scale and the Functional Independence Measure. The FARS had the greatest effect size and requires fewer patients for an equivalently powered study.Conclusions
Of the scales assessed, the FARS is the best to use in clinical trials of FRDA. This is based on effect size, and power calculations that show that fewer participants are required to demonstrate the same effect of an intervention. Further work is required to develop more sensitive and responsive instruments.Friedreich''s ataxia (FRDA) is characterised by progressive neurological symptoms and cardiac dysfunction. It results in a reduced life span.1,2 As the pathogenesis of FRDA has become better understood, several potential treatments have arisen. Initial beneficial treatments will probably slow progression rather than reverse morbidity. An appropriate and responsive scale for FRDA is critical if the benefits of potential treatments are to be identified. As there is no gold standard to examine disease progress in FRDA, the evaluation of measurement scales is essential to ensure that trials are efficient and their conclusions are accurate.3The Friedreich Ataxia Rating Scale (FARS) comprises a measure of ataxia, an activities of daily living (ADL) subscale and a neurological subscale. Face and content validity and inter‐rater reliability are good.4 Other aspects of validity have not been examined. The International Cooperative Ataxia Rating Scale (ICARS) was developed to assess pharmacotherapies in ataxia,5 and has good inter‐rater reliability.6 The Functional Independence Measure (FIM)7 and the Modified Barthel Index (MBI)8 examine the assistance required to complete ADLs. They are validated instruments used widely for neurological disease.We aimed to examine these ordinal scales proposed as outcome measures for FRDA to establish concurrent criterion validity and compare the change in score over time to determine the sensitivity of the scales and confirm which measure is most appropriate for use in clinical trials. 相似文献85.
86.
Maria A. Theodoraki Celso O. Rezende Jr. Oraphin Chantarasriwong Adriana D. Corben Emmanuel A. Theodorakis Mary L. Alpaugh 《Oncotarget》2015,6(25):21255-21267
The limited translational value in clinic of analyses performed on 2-D cell cultures has prompted a shift toward the generation of 3-dimensional (3-D) multicellular systems. Here we present a spontaneously-forming in vitro cancer spheroid model, referred to as spheroidsMARY-X, that precisely reflects the pathophysiological features commonly found in tumor tissues and the lymphovascular embolus. In addition, we have developed a rapid, inexpensive means to evaluate response following drug treatment where spheroid dissolution indices from brightfield image analyses are used to construct dose-response curves resulting in relevant IC50 values. Using the spheroidsMARY-X model, we demonstrate the unique ability of a new class of molecules, containing the caged Garcinia xanthone (CGX) motif, to induce spheroidal dissolution and apoptosis at IC50 values of 0.42 +/−0.02 μM for gambogic acid and 0.66 +/−0.02 μM for MAD28. On the other hand, treatment of spheroidsMARY-X with various currently approved chemotherapeutics of solid and blood-borne cancer types failed to induce any response as indicated by high dissolution indices and subsequent poor IC50 values, such as 7.8 +/−3.1 μM for paclitaxel. Our studies highlight the significance of the spheroidsMARY-X model in drug screening and underscore the potential of the CGX motif as a promising anticancer pharmacophore. 相似文献
87.
88.
Kristin M. Rosen Joanne E. Folker Adam P. Vogel Louise A. Corben Bruce E. Murdoch Martin B. Delatycki 《Journal of neurology》2012,259(11):2471-2477
CNS functions that show change across short periods of time are particularly useful clinical endpoints for Friedreich ataxia. This study determined whether there is measurable acoustical change in the dysarthria associated with Friedreich ataxia across yearly intervals. A total of 29?participants diagnosed with Friedreich ataxia were recorded across 4?years at yearly intervals. A repeated measures ANOVA was used to determine which acoustic measures differed across time, and pairwise t tests were used to assess the consistency of the change across the time intervals. The relationship between the identified measures with perceptual severity was assessed with stepwise regression. Significant longitudinal change was observed with four measures that relate to the utterance duration and spectral changes in utterances. The spectral measures consistently detected change across time intervals of two or more years. The four measures combined moderately predicted perceptual severity. Together, the results implicate longitudinal change in speaking rate and utterance duration. Changes in speech associated with Friedreich ataxia can be measured across intervals of 2?years and therefore show rich potential for monitoring disease progression and therapy outcomes. 相似文献
89.
90.
Cell proliferation and hair tip growth in the Arabidopsis root are under mechanistically different forms of redox control
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Sánchez-Fernández R Fricker M Corben LB White NS Sheard N Leaver CJ Van Montagu M Inzé D May MJ 《Proceedings of the National Academy of Sciences of the United States of America》1997,94(6):2745-2750
We provide evidence that the tripeptide thiol glutathione (GSH) participates in the regulation of cell division in the apical meristem of Arabidopsis roots. Exogenous application of micromolar concentrations of GSH raised the number of meristematic cells undergoing mitosis, while depletion of GSH had the opposite effect. A role for endogenous GSH in the control of cell proliferation is also provided by mapping of GSH levels in the root meristem using the GSH-specific dye monochlorobimane and confocal laser scanning microscopy. High levels of GSH were associated with the epidermal and cortical initials and markedly lower levels in the quiescent center. The mechanisms controlling cell division could also be triggered by other reducing agents: ascorbic acid and dithiothreitol. Our data also reveal significant plasticity in the relationship between the trichoblast cell length and the hair it subtends in response to alterations in intracellular redox homeostasis. While mechanisms that control trichoblast elongation are influenced by nonspecific redox couples, root hair tip growth has a more specific requirement for sulfhydryl groups. The responses we describe here may represent the extremes of redox control of root plasticity and would allow the root to maintain exploration of the soil under adverse conditions with minimal cell divisions and root hair production or capitalize on a favorable environment by production of numerous long hairs. Redox sensing of the environment and subsequent redox-dependent modulation of growth and development may be crucial components in the strategies plants have evolved for survival in a fluctuating environment. 相似文献