A5011596238- Muscle Physiology and Disorders
- Ion channel regulation and function
- Muscle activation and electromyography studies
- Pain Mechanisms and Treatments
- Muscle metabolism and nutrition
- Exercise and Physiological Responses
- Cardiomyopathy and Myosin Studies
- Anesthesia and Pain Management
- Genetic Neurodegenerative Diseases
- Genetics and Physical Performance
- Burn Injury Management and Outcomes
- Nutrition and Health in Aging
- Cholinesterase and Neurodegenerative Diseases
- Adipose Tissue and Metabolism
- Neuroscience and Neuropharmacology Research
- Biochemical effects in animals
- Meat and Animal Product Quality
- Wound Healing and Treatments
- Cardiac, Anesthesia and Surgical Outcomes
- Anesthesia and Sedative Agents
- Voice and Speech Disorders
- Transcranial Magnetic Stimulation Studies
- Electrospun Nanofibers in Biomedical Applications
- Nuclear Structure and Function
- Thermal Regulation in Medicine
Novartis (United States)
2019
Novartis (Switzerland)
2010-2013
Pfizer (United States)
2009-2011
Massachusetts General Hospital
1999-2001
Harvard University
1997-2000
Royal Victoria Hospital
1995-1999
McGill University
1994-1997
University of Cambridge
1993-1994
Cambridge School
1994
University of Nigeria
1992
The myostatin/activin type II receptor (ActRII) pathway has been identified to be critical in regulating skeletal muscle size. Several other ligands, including GDF11 and the activins, signal through this pathway, suggesting that ActRII receptors are major regulatory nodes regulation of mass. We have developed a novel, human anti-ActRII antibody (bimagrumab, or BYM338) prevent binding ligands thus inhibit downstream signaling. BYM338 enhances differentiation primary myoblasts counteracts...
Molecular mechanisms underlying sarcopenia, the age-related loss of skeletal muscle mass and function, remain unclear. To identify molecular changes that correlated best with sarcopenia might contribute to its pathogenesis, we determined global gene expression profiles in muscles rats aged 6, 12, 18, 21, 24, 27 months. These exhibit beginning at 21 Correlation versus or age changes, functional annotation analysis identified signatures distinct from aging. Specifically, mitochondrial energy...
Abstract Loss of innervation skeletal muscle is a determinant event in several diseases. Although effectors have been identified, the pathways controlling integrated response to denervation remain largely unknown. Here, we demonstrate that PKB/Akt and mTORC1 play important roles regulating homeostasis maintaining neuromuscular endplates after nerve injury. To allow dynamic changes autophagy, activation must be tightly balanced following denervation. Acutely activating or inhibiting impairs...
Sarcopenia is the progressive loss of skeletal muscle mass and function with advancing age, leading to reduced mobility quality life. We tested hypothesis that antibody-directed myostatin inhibition would attenuate decline in muscles aged mice apoptosis be reduced. Eighteen-month-old C57BL/6 were treated for 14 wk a once-weekly injection saline (control, n=9) or mouse chimera anti-human antibody (PF-354, 10 mg/kg; n=12). PF-354 prevented age-related reduction body increased soleus,...
HDAC4, a class IIa histone deacetylase, is upregulated in skeletal muscle response to denervation-induced atrophy. When HDAC4 deleted postnatally, mice are partially protected from denervation. Despite the name "histone" demonstrably deacetylates cytosolic and non-histone nuclear proteins. We developed potent selective HDAC inhibitors. Using these tools genetic knockdown, we identified three previously unidentified substrates of HDAC4: myosin heavy chain, peroxisome proliferator-activated...
Declines in skeletal muscle size and strength, often seen with chronic wasting diseases, prolonged or high-dose glucocorticoid therapy, the natural aging process mammals, are usually associated reduced physical activity testosterone levels. However, it is not clear whether decline causally related. Using a mouse model, we found that removal of endogenous by orchidectomy results an almost complete cessation voluntary wheel running but only small mass. Testosterone replacement restored...
Counteracting the atrophy of skeletal muscle associated with disuse has significant implications for minimizing wasting and weakness in plaster casting, joint immobilization, other forms limb unloading, relevance to orthopedics, sports medicine, plastic reconstructive surgery. We tested hypothesis that antibody-directed myostatin inhibition would attenuate loss mass functional capacity mice during 14 or 21 days unilateral hindlimb casting. Twelve-week-old C57BL/10 were subjected casting...
Progressive loss of muscle mass and function due to fiber atrophy in the elderly chronically ill is now defined as sarcopenia. It a major contributor independence, disability, need long-term care well overall mortality. Sarcopenia heterogenous disease underlying mechanisms are not completely understood. Here, we newly identified used Tmem158, alongside Cdkn1a, relevant senescence denervation markers (SDMs), associated with atrophy. Subsequent application laser capture microdissection (LCM)...
In muscle, the kinase-dependent and -independent functions of MNK2 inhibit protein translation eIF4G under conditions that promote atrophy.
Objectives Muscle weakness associated with critical illness can be due to the itself, immobilization it, and/or concomitant use of drugs that affect neuromuscular transmission. This study investigated contribution per se muscle dysfunction, as well morphologic and biochemical changes. Design Prospective, laboratory study. Setting Hospital research laboratory. Subjects Adult, male, Sprague-Dawley rats, weighing 200 250 g, were randomly allocated three experimental groups, depending on...
Abstract This study tested the hypotheses that burn‐induced change in muscle function varies at sites local and distant from burn is related to changes expression of acetylcholine receptors (AChRs) mass. In anesthetized rats, ∼4% was inflicted over tibialis anterior one limb. The contralateral leg served as control. another study, a ∼45% body surface area produced on trunk; controls were sham‐burned rats. evoked twitch tensions muscles both legs measured together with AChR proteins their...
This study investigated whether immobilization-induced hyposensitivity to d-tubocurarine (dTC), up-regulation of acetylcholine receptors (AChRs) and changes in fiber size motor endplate persist indefinitely they are causally related. Unilateral disuse the tibialis muscle was produced adult rats by pinning knee ankle joints at 90 degrees flexion. The contralateral unpinned a separate group sham-pinned legs served as controls. After 7, 14 or 28 days disuse, vivo dose dTC that 50% depression...
We tested the hypothesis that resistance to d-tubocurarine (dTC) is more intense in muscles closer to, than distant from, burn, and related expression of immature total acetylcholine receptors (AChRs). Anesthetized rats received approximately 4% surface area burn over tibialis muscle one leg with contralateral serving as control, or 45% flank sham-burned pair fed controls. At 1, 4, 7, 14 days later, 50% effective dose dTC, membrane AChRs, messenger ribonucleic acid (mRNA) encode AChR...
Large doses of glucocorticoids can alter muscle physiology and susceptibility to neuromuscular blocking drugs by mechanisms not clearly understood. We investigated the effects moderate large prednisolone on function pharmacology, their relationship changes in size acetylcholine receptor (AChR) expression. With institutional approval, 35 Sprague-Dawley rats were randomly allocated receive daily subcutaneous 10 mg/kg (P10 group), 100 (P100 or an equal volume saline (S group) for 7 days. A...
Effects of cassava ( Manihot esculenta Crantz )-borne organic cyanide and inorganic in the form sodium on bone muscle development were investigated eighteen dogs Nigerian breed. After 16 weeks stabilization laboratory from time purchase when fed same diet, they randomly assigned to three experimental groups six each. The control group was rice while other two either (gari) or plus cyanide. diets made isoenergetic isonitrogenous by varying quantity meat incorporated into them. results...
Tacrine (THA) is an anticholinesterase drug used to manage Alzheimer's dementia, but it not clear how its chronic use might affect response nondepolarizing muscle relaxants. We determined the magnitude and time course of effects oral THA intravenous (IV) on d-tubocurarine (dTC) blockade at soleus tibialis muscles. Six groups adult rats were given 10 mg/kg twice daily by gavage for 1, 2, 4, or 8 wk (chronic groups), 1 mL saline 1-8 (control), IV approximately 20 min before (acute), cumulative...