Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0002736 (amyotrophic lateral sclerosis)
 19,048 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In our preceding companion paper (Wang Y, Winters J, Subramaniam S. J Appl Physiol. doi: 10.1152/japplphysiol.01514.2011), we used extensive expression profile data on normal human subjects, in combination with legacy knowledge to classify skeletal muscle function into four models, namely excitation-activation, mechanical, metabolic, and signaling-production model families. In this paper, we demonstrate how this classification can be applied to study two well-characterized myopathies: amyotrophic lateral sclerosis (ALS) and Duchenne muscular dystrophy (DMD). Using skeletal muscle profile data from ALS and DMD patients compared with that from normal subjects, normal young in the case of DMD, we delineate molecular mechanisms that are causative and consequential to skeletal muscle dysfunction. In ALS, our analysis establishes the metabolic role and specifically identifies the mechanisms of calcium dysregulation and defects in mitochondrial transport of materials as important for muscle dysfunction. In DMD, we illustrate how impaired mechanical function is strongly coordinated with other three functional networks, resulting in transformation of the skeletal muscle into hybrid forms as a compensatory mechanism. Our functional models also provide, in exquisite detail, the mechanistic role of myriad proteins in these four families in normal and disease function.
 ...
PMID:Functional classification of skeletal muscle networks. II. Applications to pathophysiology. 2308 57

For generations, the neuromuscular disorder care community has focused on establishing the correct diagnosis and providing supportive care. As the pathophysiology and genetics of these conditions became better understood, novel treatments targeting the disease mechanism were developed. This has led to some significant disease-modifying and supportive treatments for several neuromuscular disorders. The current treatments for amyotrophic lateral sclerosis (ALS), neuromuscular junction disorders, inflammatory myopathies, and myotonia are reviewed. Additionally, investigational treatments for ALS, Duchenne muscular dystrophy, and spinal muscular atrophy are discussed.
 ...
PMID:Current pharmacologic management in selected neuromuscular diseases. 2313 38

This article reviews the recent literature regarding bone health as it relates to the patient living with neuromuscular disease (NMD). Studies defining the scope of bone-related disease in NMD are scant. The available evidence is discussed, focusing on abnormal calcium metabolism, increased fracture risk, and the prevalence of both scoliosis and hypovitaminosis D in Duchenne muscular dystrophy, amyotrophic lateral sclerosis, and spinal muscular atrophy. Future directions are discussed, including the urgent need for studies both to determine the nature and extent of poor bone health, and to evaluate the therapeutic effect of available osteoporosis treatments in patients with NMD.
 ...
PMID:Bone health and associated metabolic complications in neuromuscular diseases. 2313 37

This article discusses the role of palliative care in the treatment pathway of patients with progressive neuromuscular disease (NDM), including amyotrophic lateral sclerosis and Duchenne muscular dystrophy (DMD). People with severe NMDs like DMD are now living much longer, well in to adulthood. This makes them suitable for the medical model of palliative care. Yet palliative medicine is a new area, especially for "adults" with DMD. Strategies for identifying the most effective modalities to alleviate suffering in patients with an NMD receiving palliative services and creating best practice standards in pain and symptom management for this patient population are discussed.
 ...
PMID:Using palliative care in progressive neuromuscular disease to maximize quality of life. 2313 45

Linking gene defect to disease phenotypes in mice has become an essential step in the development of new drugs. Yet, many in vitro and in vivo assays require anaesthetic and surgery or do not reflect physiologically relevant phenomena. The effects of genes or diseases may only become apparent with stressors. Here, we apply non-invasive ECG monitoring and gait imaging systems to describe changes in the electrocardiogram and in gait dynamics resulting from a doubling of the ambulatory speed of mice. We found that B6C3H mice (n = 5) take 3.6 +/- 0.1 strides/second to walk 18cm/second and have a heart rate of 750 +/- 2bpm after 1 minute of walking at this speed. These mice significantly increase stride frequency to 5.2 +/- 0.1 strides/second in order to increase their speed to 36cm/second. The heart rate increased significantly (814 +/- 9bpm, p < 0.05) after trotting at the higher speed for 90 seconds, and the QRS interval duration significantly decreased (9.4 +/- 0.3ms vs. 10.4 +/- 0.3ms, p < 0.05). We discuss the application of the ECG screening and gait imaging systems to mouse models of Duchenne muscular dystrophy, Down syndrome and amyotrophic lateral sclerosis, diseases in humans that are known to affect the heart and neuromuscular systems.
 ...
PMID:Non-invasive physiology in conscious mice. 2357 59

In amyotrophic lateral sclerosis (ALS), a recent double-blind placebo-controlled trial of acetyl-L-carnitine along with riluzole showed probable benefit in 42 patients compared with 40 patients who received placebo. Using an electrophysiologic measure devised to differentiate ALS from other neuromuscular conditions, a "splint-hand index" was devised and is reviewed. Analysis of skin in ALS may also be of interest, and there was a report of accumulation of fused in sarcoma protein in the epidermis of ALS patients. With regard to myasthenia gravis, there is another report that early treatment of ocular symptoms with corticosteroids may prevent the development of generalized symptoms. A new study of thymus histopathology in muscle-specific tyrosine kinase (MuSK) myasthenia gravis is covered and another article on the use of thymectomy. In Duchenne muscular dystrophy, the best method of administrating corticosteroids is still being debated, and a long-term study of daily versus intermittent prednisolone is reviewed. The study showed less sustained benefit from the intermittent prednisolone but with a better side effect profile. According to 2 recent reports, it seems that titin mutations may be an underrecognized cause of myopathy with early respiratory failure in adults. Keeping with the respiratory failure theme, there was also an interesting article on the long-term benefits and side effects of cyclosporine in patients with interstitial lung disease from antisynthetase syndrome. Finally, the spectrum of small fiber neuropathy may be expanding to include a causative role in some patients with fibromyalgia syndrome and in juveniles with diffuse pain and a possible autoimmune predisposition.
...
PMID:What's in the literature? 2396 8

Antisense therapy is an approach to fighting diseases using short DNA-like molecules called antisense oligonucleotides. Recently, antisense therapy has emerged as an exciting and promising strategy for the treatment of various neurodegenerative and neuromuscular disorders. Previous and ongoing pre-clinical and clinical trials have provided encouraging early results. Spinal muscular atrophy (SMA), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), Duchenne muscular dystrophy (DMD), Fukuyama congenital muscular dystrophy (FCMD), dysferlinopathy (including limb-girdle muscular dystrophy 2B; LGMD2B, Miyoshi myopathy; MM, and distal myopathy with anterior tibial onset; DMAT), and myotonic dystrophy (DM) are all reported to be promising targets for antisense therapy. This paper focuses on the current progress of antisense therapies in neurology.
...
PMID:Antisense therapy in neurology. 2556 50

MicroRNAs (miRNAs) have recently emerged as fundamental post-transcriptional regulators inhibit gene expression linked to various biological processes. MiR-206 is one of the most studied and best characterized miRNA to date, which specifically expressed in skeletal muscle. In this review, we summarized the results of studies of miR-206 with emphasis on its function in skeletal muscle development. Importantly, dysregulation of miR-206 has been linked to many disorders in skeletal muscle such as Duchenne muscular dystrophy (DMD) and amyotrophic lateral sclerosis (ALS), and circulating miR-206 has highlighted its potential as a diagnose biomarker. In addition, a mutation in the 3' untranslated region (3'-UTR) of the myostatin gene in the Texel sheep creating a target site for the miR-206 and miR-1 leads to inhibition of myostatin expression, which likely to cause the muscular hypertrophy phenotype of this breed of sheep. Therefore, miR-206 may become novel target for ameliorating skeletal muscle-related disorders and optimization of muscle quantity of domestic animals.
...
PMID:MiR-206, a key modulator of skeletal muscle development and disease. 2567 53

Dysphagia is one of the most critical problems in patients with progressive neuromuscular diseases. However, clinically useful and practical scales to evaluate dysphagia are limited. Therefore, the aim of this study was to develop such a scale. An 8-stage Neuromuscular Disease Swallowing Status Scale (NdSSS) was developed and tested for its inter- and intrarater reliabilities, concurrent validity, and responsiveness. The NdSSS was used to evaluate 134 patients with Duchenne muscular dystrophy (DMD) and 84 patients with amyotrophic lateral sclerosis (ALS). Inter- and intrarater reliabilities were examined with weighted kappa statistics. Concurrent validity was assessed by correlating the NdSSS with the existing scales [Functional Oral Intake Scale (FOIS), Functional Intake LEVEL Scales (FILS), and ALS Functional Rating Scale-Revised Swallow (ALSFRS-R Sw)], using Spearman's correlation coefficients. Responsiveness was determined with the standardized response mean (SRM). For inter- and intrarater reliabilities, the weighted kappas were 0.95 and 1.00, respectively, for DMD; and 0.98 and 0.98, respectively, for ALS. The NdSSS showed strong correlations with the FOIS (rs = 0.87 for DMD, rs = 0.93 for ALS, p < 0.001), FILS (rs = 0.89 for DMD, rs = 0.92 for ALS, p < 0.001), and ALSFRS-R SW (rs = 0.93, p < 0.001). SRMs were 0.65 for DMD and 1.21 for ALS. The SRM was higher in DMD patients for the NdSSS than for the other scales, while it was similar in ALS patients and the other scales. Our originally developed NdSSS demonstrated sufficient reliability, validity, and responsiveness in patients with DMD and ALS. It is also useful in evaluating dysphagia in patients with progressive neuromuscular diseases.
 ...
PMID:Development of a new scale for dysphagia in patients with progressive neuromuscular diseases: the Neuromuscular Disease Swallowing Status Scale (NdSSS). 2614 25

Neuromuscular diseases can affect all respiratory muscles, leading to acute respiratory failure, which is the most common cause of morbidity and mortality in those patients. Two situations must be distinguished. 1) Acute respiratory failure as part of a neuromuscular disorder of acute onset and possibly reversible (Guillain-Barre syndrome, myasthenic crisis...). 2) Acute respiratory failure occurring in a patient with an already advanced neuromuscular disease (amyotrophic lateral sclerosis, Duchenne muscular dystrophy...). This article describes the neuromuscular acute respiratory failure in these different aspects, discusses its initial management in the emergency department and identifies the parameters that have to be monitored.
 ...
PMID:[Acute respiratory failure in neuromuscular disease]. 2661 4


<< Previous 1 2 3 4 5 6 7 8 Next >>