Musculoskeletal, Neural, and Ocular Physiology Commons^™

Expanding The Role Of Muscle Stem Cell Fusion In Muscle Under Hypertrophic Stimulus, Jensen Goh Zhong Sheng

Theses and Dissertations--Physiology

Muscle stem cells (MuSCs) are a unique stem cell population that can activate in response to both injury and growth stimuli. Studies on muscle regeneration have shown MuSC activation follows a uniform progression through proliferation, differentiation, and fusion. Therefore, to determine whether MuSC replication is a prerequisite for differentiation under hypertrophic stimulus, I used a lineage-tracking mouse model (Pax7^rtTA; TRE-H2B-GFP) to label MuSC nuclei and simultaneously tracked DNA synthesis via EdU incorporation. This dual-labeling approach allowed us to not only distinguish MuSC-derived nuclei but also demarcate which MuSC had proliferated prior to fusion. I then employed a mechanical …

Mitochondria As Causes Of And Therapeutic Targets In Chronic Post-Sepsis Skeletal Muscle Weakness, Meagan Scott Kingren

Theses and Dissertations--Pharmacology and Nutritional Sciences

Sepsis, or the organ damage that ensues after the body fails to properly contain a local infection, is the leading cause of in-patient hospitalization in the United States. Advances in critical care medicine over the last 20 years have enabled most sepsis patients to survive the life-threatening dysregulated immune response. However, a majority of survivors report chronic weakness and fatigue years after sepsis, and the cause of this weakness remains largely unknown. This dissertation work focused first on elucidating the major causes of post-sepsis muscle weakness (Aim 1). This aim involved a time-course study to determine when muscle weakness was …

Changes In Muscle Size, Quality And Power Are Related To Physical Function In Patients With Critical Illness, Kirby Mayer

Theses and Dissertations--Rehabilitation Sciences

Patients admitted to intensive care unit (ICU) are known to develop significant impairments in physical function. Patients with critical illness suffer up to 30% reductions in muscle size within the first ten days of admission to the ICU. Muscle strength testing, Medical Research Council-sum score, is current gold-standard to diagnosis ICU-acquired weakness and predicts risk of mortality and long-term physical function. Muscle power different from muscle strength in that it accounts for velocity of movement, is potentially a better independent predictor of function that has not been studied in this population. In addition, we hypothesize that muscle size and quality …

Longitudinal Screening Detects Cognitive Stability And Behavioral Deterioration In Als Patients, Susan Woolley, Ray Goetz, Pam Factor-Litvak, Jennifer Murphy, Jonathan Hupf, Catherine Lomen-Hoerth, Howard Andrews, Daragh Heitzman, Richard Bedlack, Jonathan Katz, Richard Barohn, Eric Sorenson, Bjorn Oskarsson, Americo Fernandes Filho, Edward J. Kasarskis, Tahseen Mozaffar, Sharon Nations, Andrea Swenson, Agnes Koczon-Jaremko, Georgia Christodoulou, Hiroshi Mitsumoto

Neurology Faculty Publications

Objective. To evaluate longitudinal cognitive/behavioral change over 12 months in participants enrolled in the ALS Multicenter Cohort Study of Oxidative Stress (ALS COSMOS). Methods. We analyzed data from 294 ALS participants, 134 of whom were studied serially. Change over time was evaluated controlling for age, sex, symptom duration, education, race, and ethnicity. Using multiple regression, we evaluated associations among decline in ALS Functional Rating Scale-Revised (ALSFRS-R) scores, forced vital capacity (FVC), and cognitive/behavioral changes. Change in cognitive/behavioral subgroups was assessed using one-way analyses of covariance. Results. Participants with follow-up data had fewer baseline behavior problems compared to patients …

Physiological Differences Between Low Versus High Skeletal Muscle Hypertrophic Responders To Resistance Exercise Training: Current Perspectives And Future Research Directions, Michael D. Roberts, Cody T. Haun, Christopher B. Mobley, Petey W. Mumford, Matthew A. Romero, Paul A. Roberson, Christopher G. Vann, John J. Mccarthy

Physiology Faculty Publications

Numerous reports suggest there are low and high skeletal muscle hypertrophic responders following weeks to months of structured resistance exercise training (referred to as low and high responders herein). Specifically, divergent alterations in muscle fiber cross sectional area (fCSA), vastus lateralis thickness, and whole body lean tissue mass have been shown to occur in high versus low responders. Differential responses in ribosome biogenesis and subsequent protein synthetic rates during training seemingly explain some of this individual variation in humans, and mechanistic in vitro and rodent studies provide further evidence that ribosome biogenesis is critical for muscle hypertrophy. High responders may …

Bilateral Facial Spasm Following Guillain-Barré Syndrome, Zain Guduru, John Morgan, Kapil Sethi

Neurology Faculty Publications

Background: We report a patient who developed lower facial muscle spasm at rest and bilateral facial synkinesis several months after treatment of Guillain–Barré syndrome (GBS); this finding, to our knowledge, is hitherto unreported.

Phenomenology Shown: Bilateral synkinesis, facial muscles spasm at rest, bilateral postparalytic facial syndrome.

Educational Value: Aberrant regeneration of nerve fibers post GBS, resulting in facial muscles spasm at rest, bilateral synkinesis.

Interactions Of Primary Insult Biomechanics And Secondary Cascades In Spinal Cord Injury: Implications For Therapy, Michael B. Orr, John C. Gensel

Spinal Cord and Brain Injury Research Center Faculty Publications

No abstract provided.

Tumor-Derived Proteins And Mitochondrial Dysfunction In Lung Cancer-Induced Cachexia, Julie B. Mclean

Theses and Dissertations--Physiology

Lung tumors secrete multiple factors that contribute to cachexia, a severe wasting syndrome that includes loss of muscle mass, weakness, and fatigue. 80% of advanced lung cancer patients experience cachexia, which cannot be reversed by nutritional interventions, diminishes response to and tolerance of cancer treatments, and increases morbidity and mortality. Despite a multitude of clinical trials, there are currently no approved treatments. This deficiency suggests that not all of the factors that contribute to cachexia have been identified.

Cancer is frequently accompanied by an increase in cyclooxygenase-2 (COX-2), a hallmark of inflammation. Clinical trials for COX-2 inhibitors have resulted in …

The Skeletal Muscle Molecular Clock Regulates The Timing Of Substrate Metabolism And The Circadian Expression Of Titin-Cap, Brian A. Hodge

Theses and Dissertations--Physiology

Skeletal muscle is a major contributor to whole-body metabolism as it serves as a depot for both glucose and amino acids, and is a highly metabolically active tissue. An intrinsic molecular clock mechanism exists within skeletal muscle that regulates the timing of physiological processes. A key function of the clock is to regulate the timing of metabolic processes to anticipate time of day changes in environmental conditions. The purpose of this study was to identify metabolic genes that are expressed in a circadian manner and determine if these genes are regulated downstream of the intrinsic molecular clock by assaying gene …

Transmural Heterogeneity Of Cellular Level Cardiac Contractile Properties In Aging And Heart Failure, Premi Haynes

Theses and Dissertations--Physiology

The left ventricle of the heart relaxes when it fills with blood and contracts to eject blood into circulation to meet the body’s metabolic demands. Dysfunction in either relaxation or contraction of the left ventricle can lead to heart failure. Transmural heterogeneity is thought to contribute to normal ventricular wall motion but it is not well understood how transmural modifications affect the failing left ventricle. The overall hypothesis of this dissertation is that normal left ventricles exhibit transmural heterogeneity in cellular level contractile properties and with aging and heart failure there are region-specific changes in cellular level contractile mechanisms.

Age …