Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0011168 (dysphagia)
 15,644 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Amyotrophic lateral sclerosis (ALS) is a typical intractable disease affecting the primary and secondary motoneurones resulting in generalized muscular atrophy and weakness with or without spasticity. Dysphagia, dysarthria, and respiratory difficulty are symptoms which cause restriction of ADL and death. Recent achievement in understanding neuronal death in ALS has invited trials on various drugs aiming at neuroprotection and prolongation of the course of ALS. They include inhibition of excitotoxicity of amino acids, suppression of free radicals by lecithinized SOD and various neurotrophic factors. Significant prolongation of life span was obtained by riluzole in a US-Europe trial, but the effects were insignificant in the Japanese nation-wide trial.
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PMID:[Neuroprotective therapy for amyotrophic lateral sclerosis (ALS)]. 912 96

1. Amyotrophic lateral sclerosis (ALS) is a degenerative disorder characterized by selective damage to the neural system that mediates voluntary movement. Although the pathophysiologic process of ALS remains unknown, about 5 to 10% of cases are familial. According to genetic linkage studies, the familial ALS (FALS) gene has been mapped on chromosome 21 in some families and recent work identified some different missense mutations in the Cu/Zn superoxide dismutase gene in FALS families. 2. We recently identified five mutations in six FALS families. The mutations identified in our FALS families are H46R, L84V, I104F, S134N, and V148I. The H46R mutation that locates in the active site of Cu/Zn SOD gene is associated with two Japanese families with very slow progression of ALS. On the other hand, the L84V mutation associated with a rapidly progressive loss of motor function with predominant lower motor neuron manifestations. 3. In the family with the V148I, the phenotype of the patient varied very much among the affected members. One case had weakness of the lower extremities at first and died without bulbar paresis. The second case first noticed wasting of the upper limbs with bulbar symptoms, but the third had weakness of upper extremities without developing dysarthria nor dysphagia until death. These mutations account for 50% of all FALS families screened, although Cu/Zn SOD gene mutations are responsible for less than about 13-21% in the Western population. 4. Our results indicate that the progression of disease with mutations of Cu/Zn SOD is well correlated with each mutation. The exact mechanism by which the abnormal Cu/Zn SOD molecules selectively affect the function of motor neurons is still unknown.
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PMID:Molecular analyses of the Cu/Zn superoxide dismutase gene in patients with familial amyotrophic lateral sclerosis (ALS) in Japan. 987 71

We report a Japanese family with autosomal dominant adult-onset amyotrophic lateral sclerosis (FALS) with onset in the bulbar musculature, clinically benign course, absence of the Cu/Zn superoxide dismutase-1 (SOD 1) gene mutation, and many Bunina bodies, in addition to involvement of the upper and lower motor neurons. The proband was a Japanese woman who was 66 years old at the time of death. Family history disclosed five patients with FALS over three generations. She developed dysarthria at age 57, followed by dysphagia, muscle weakness of the upper extremities, and difficulty in respiration. She could walk without support until her death. The elder sister of the proband developed dysarthria at age 48 and died at age 58. A genetic study of the nephew of the proband showed the absence of a mutation in the SOD 1 gene. Neuropathological examination of the proband disclosed neuronal loss in the upper and lower motor neurons, and numerous Bunina bodies in the lower motor neurons without Lewy body-like inclusions or ubiquitin-immunoreactive neuronal inclusions. No degeneration of the Clarke's column, middle root zone of the posterior column, or posterior spinocerebellar tract was present. Review of the literature revealed that only patients with FALS with a long survival period of over 5 years had pathological findings consistent with FALS with posterior column involvement. This study contributes to the elucidation of the clinicopathological heterogeneity of FALS.
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PMID:Familial amyotrophic lateral sclerosis with onset in bulbar sign, benign clinical course, and Bunina bodies: a clinical, genetic, and pathological study of a Japanese family. 1107 11