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)

Polymyositis (PM) is a cell-mediated autoimmune disease. Perforin (PF), Fas ligand (FasL) and TNF-alpha are considered to be important factors in cytotoxic T lymphocyte-mediated cell injury, and several studies have established a role of lymphotoxin (LT) in T helper type 1 (Th1)-induced cell-mediated autoimmune diseases. In the present study, to determine how LT, PF and FasL are involved in the pathogenesis of PM, we used immunohistochemical staining (IHC), reverse transcription polymerase chain reaction (RT-PCR), and in situ hybridization (ISH) on muscle specimens from patients with PM, amyotrophic lateral sclerosis (ALS), myotonic dystrophy (MyD) and controls (NC). There were many mononuclear cells (MNCs) immunoreactive for LT and some for PF and FasL within the fasciculus in PM muscles. On the other hand, only few or no LT-, PF- and FasL-positive cells were detected in MyD, ALS and NC muscles. The results of mRNA expression of these three molecules with RT-PCR were consistent with those using IHC methods. The number of MNCs positive for LT with ISH was far higher in PM compared to MyD, ALS and NC (P < 0.05 or 0.01). The MNCs located in the connective tissue or in the vicinity of necrotizing or non-necrotizing muscles were mainly LT mRNA and CD4 positive, while MNCs invading the non-necrotic fibers were mainly LT mRNA and CD8 positive. Our results indicated that the expression of LT was up-regulated in PM, and LT plays an important role in muscle injury and orchestrating the inflammatory reaction in PM.
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PMID:The role of lymphotoxin in pathogenesis of polymyositis. 1104 74

We investigated gene expression patterns of ion channels including the apamin-sensitive small-conductance Ca(2+)-activated K(+) (SK3) channel, the adult isoform of the skeletal muscle Na(+) channel (SkM1), the fetal isoform of skeletal muscle Na(+) channel (H1), and the Cl(-) channel (ClC-1) by using the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for muscle samples from patients with adult onset myotonic dystrophy (DM), amyotrophic lateral sclerosis, and polymyositis. Patients with DM showed a significant increase in SK3 mRNA but not in mRNAs for other ion channels. The increased expression of SK3 gene in DM did not correlate with H1, the marker of muscle denervation, or the percentage of type 2C fiber, the marker of muscle regeneration.
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PMID:The expression of ion channel mRNAs in skeletal muscles from patients with myotonic muscular dystrophy. 1109 Sep 82

Neuromuscular and chest wall disorders are individually uncommon but together form an important group of conditions that can lead to chronic ventilatory failure. This is best recognised in scoliosis, kyphosis, following a thoracoplasty, in muscular dystrophies, such as Duchenne muscular dystrophy (DMD), and myotonic dystrophy, after poliomyelitis and with motor neurone disease (amyotrophic lateral sclerosis). If bulbar function is impaired, tracheostomy ventilation may be required, but in other situations, noninvasive ventilation is preferable. Positive pressure techniques using nasal and face masks are usually the first choice, but negative pressure ventilation is an alternative. There are no randomised-controlled trials regarding the indications for initiating noninvasive ventilation, but this is usually provided if there are symptoms due to nocturnal hypoventilation or right heart failure in the presence of a raised carbon dioxide tension in arterial blood (Pa,CO2) either at night or, more usually, in the daytime as well. There is no evidence that "prophylactic" ventilatory support is of benefit if this is provided before ventilatory failure has appeared. Careful selection of patients is required, especially in the presence of progressive neuromuscular disorders such as DMD and motor neurone disease. There are no randomised-controlled trials concerning the outcome of noninvasive ventilation in these conditions, but studies have shown an improved quality of life, physical activity and haemodynamics, normalisation of blood gases and slight improvement in other physiological measures, such as the vital capacity and maximal mouth pressures. Survival in chest wall disorders is approximately 90% at 1 yr and 80% at 5 yrs, and similar figures have been obtained in nonprogressive neuromuscular conditions. If, however, the underlying disorder is deteriorating, particularly if it involves the bulbar muscles, it may limit survival despite the provision of adequate noninvasive ventilatory support.
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PMID:Noninvasive ventilation for chest wall and neuromuscular disorders. 1508 69

The SK3 channel, a small-conductance calcium-activated potassium channel, is expressed in immature fibers of skeletal muscle and becomes down regulated after innervation. We have previously shown that the level of mRNA of the SK3 channel is increased in muscle from myotonic dystrophy. In this study, we have carried out an immunohistochemical study using a polyclonal anti-SK3 antibody. SK3 protein is partly expressed at the cell membrane of normal sized fibers in myotonic dystrophy. Although SK3 channels are also expressed in muscles from polymyositis and amyotrophic lateral sclerosis, the positive staining is observed only in regenerating or denervated fibers. No expression of SK3 protein in a myotonic mouse (ADR) suggests that the increase in the SK3 channel in myotonic dystrophy is not due to hyperexcitability. These data support the hypothesis of a differentiation defect in myotonic dystrophy.
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PMID:Expression and distribution of a small-conductance calcium-activated potassium channel (SK3) protein in skeletal muscles from myotonic muscular dystrophy patients and congenital myotonic mice. 1287 18

Insulin-like growth factor-I (IGF-I) has endocrine, autocrine and paracrine properties. Receptors for IGF-I are present on virtually all cell types but are located mainly on cells of mesenchymal origin, such as fibroblasts, chondrocytes and osteoblasts. Growth hormone (GH)-dependent and GH-independent actions of IGF-I have been implicated in normal and abnormal bone growth, diabetes mellitus, malnutrition, cancer, thyroid disease and hematological diseases. The availability of recombinant human IGF-I (rhIGF-I) has led to new treatments for GH-resistant Laron dwarfism and certain diseases associated with severe insulin resistance. IGF-I has recently been investigated as a neurotrophic factor. Phase II efficacy trials with patients with neurological disease such as traumatic brain injury, myotonic dystrophy and amyotrophic lateral sclerosis have shown that rhIGF-I has efficacy on various outcome parameters. Treatment with rhIGF-I may result in reversible side effects of which increased heart rate, papilledema, ophthalmologic and intracranial hypertension, facial and generalized edema, and weight gain are noteworthy.
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PMID:Insulin-like growth factor-I: clinical studies. 1509 66

Intermittent indirect hyperbilirubinemia was occasionally observed in Duchenne muscular dystrophy (DMD) patients. We suspected that hyperbilirubinemia might be caused by hemolysis of fragile erythrocytes due to damaged endothelium, which was reported in DMD. To examine the fragility of erythrocytes, we performed osmotic resistance test in 25 DMD, 12 myotonic dystrophy (DM), 12 amyotrophic lateral sclerosis (ALS) and 24 healthy volunteers (male 15, female 9). Minimum resistance (beginning point of hemolysis) of DMD (0.447 +/- 0.016%) was higher than that of age matched male controls (0.425 +/- 0.018%: p = 0.0008) and that of DM (0.440 +/- 0.015%) was also higher than that of total controls (0.423 +/- 0.016%, p = 0.0077). The number of poikilocytes was increased in DMD (35.45 +/- 41.17 per a high magnitude field), however no obvious correlation was detected between the ratio of poikilocytes and resistances. Total bilirubin showed correlation (p = 0.029) to minimum resistance. These findings suggested that erythrocyte membrane is fragile in DMD. Involvement of endothelial damage could not be proven, because all investigated patients showed normal tissue plasminogen activator inhibitor-1. Although the mechanism of fragile erythrocytes in DMD is still unknown, we should pay attention to interpret bilirubin in DMD, because hemolysis due to erythrocyte fragility may influence the value.
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PMID:[Erythrocyte from Duchenne muscular dystrophy is fragile]. 1556 87

Several studies have suggested the presence of central nervous system involvement manifesting as cognitive impairment in diseases traditionally confined to the peripheral nervous system. The aim of this review is to highlight the character of clinical, genetic, neurofunctional, cognitive, and psychiatric deficits in neuromuscular disorders. A high correlation between cognitive features and cerebral protein expression or function is evident in Duchenne muscular dystrophy, myotonic dystrophy (Steinert disease), and mitochondrial encephalomyopathies; direct correlation between tissue-specific protein expression and cognitive deficits is still elusive in certain neuromuscular disorders presenting with or without a cerebral abnormality, such as congenital muscular dystrophies, congenital myopathies, amyotrophic lateral sclerosis, adult polyglucosan body disease, and limb-girdle muscular dystrophies. No clear cognitive deficits have been found in spinal muscular atrophy and facioscapulohumeral dystrophy.
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PMID:Cognitive impairment in neuromuscular disorders. 1654 20

In this Review, familial and sporadic neurological disorders reported to have an etiological link with DNA repair defects are discussed, with special emphasis placed on the molecular link between the disease phenotype and the precise DNA repair defect. Of the 15 neurological disorders listed, some of which have symptoms of progeria, six--spinocerebellar ataxia with axonal neuropathy-1, Huntington's disease, Alzheimer's disease, Parkinson's disease, Down syndrome and amyotrophic lateral sclerosis--seem to result from increased oxidative stress, and the inability of the base excision repair pathway to handle the damage to DNA that this induces. Five of the conditions (xeroderma pigmentosum, Cockayne's syndrome, trichothiodystrophy, Down syndrome, and triple-A syndrome) display a defect in the nucleotide excision repair pathway, four (Huntington's disease, various spinocerebellar ataxias, Friedreich's ataxia and myotonic dystrophy types 1 and 2) exhibit an unusual expansion of repeat sequences in DNA, and four (ataxia-telangiectasia, ataxia-telangiectasia-like disorder, Nijmegen breakage syndrome and Alzheimer's disease) exhibit defects in genes involved in repairing double-strand breaks. The current overall picture indicates that oxidative stress is a major causative factor in genomic instability in the brain, and that the nature of the resulting neurological phenotype depends on the pathway through which the instability is normally repaired.
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PMID:Mechanisms of disease: DNA repair defects and neurological disease. 1734 92

Summary of Neuromuscular Presentations at the 57 Annual AAN 2005 meeting in Miami Florida on topics of Facioscapulohumeral muscular dystrophy (FSHD), Duchenne muscular dystrophy (DMD), Diabetic Neuropathy, Charco Marie Tooth disease (CMT), Comparison of injected steroids versus Surgery for carpal tunnel syndrome, Rituximab in Anti-MAG associated polyneuropathy, Cannabis based medicine (CBM) in the treatment of neuropathic pain, utility of skin biopsy with intraepidermal nerve fiber density (IENFD) in sensory complaints, comparing sympathetic skin responses (SSRs) and skin biopsy in diagnosing small fiber sensory neuropathy, Chronic inflammatory demyelinating polyneuropathy (CIDP) clinical and electrophysiologic predictors, affect of limb warming in mild ulnar nerve conduction study (NCS) abnormalities, Tamoxifen affect in ALS, open label study of 3,4 DAP, Pyridostigmine and Ephedrine in fast channel syndrome, Mexilitine as an antimyotonia treatment in myotonic dystrophy (DM1), frontal lobe impairment evaluation in DM1 and DM2 patients and phenotype-genotype correlation in patients with dysferlinopathy.
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PMID:Neuromuscular Highlights-AAN 2005. 1907 9

Peripheral neuropathies are among the most common disorders seen by neuromuscular specialists. Several of the articles in this issue's review focus on diagnosis, treatment, and prognosis of disorders of peripheral nerve, including some which address important issues relating to chronic inflammatory demyelinating polyneuropathy. Motor neuron diseases continue to be somewhat disproportionately represented, likely due to the devastating nature of amyotrophic lateral sclerosis. The TAR DNA-binding protein-43 (TDP-43) story as outlined in 2 of the articles is fascinating, particularly with regard to etiopathogenesis, whereas other articles focus on epidemiology, diagnosis, treatment, and symptom management, including some insights into Kennedy disease. Myotonic dystrophy and other muscle diseases are presented with some welcome news on treatment and management.
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PMID:What's in the Literature? 1949 33


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