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

Antibodies to ubiquitin have been used to search for evidence of abnormal protein degradation in amyotrophic lateral sclerosis--motor neuron disease (ALS). Anterior horn cell ubiquitin-immunoreactive (IR) inclusions were present in all of 31 ALS cases but in none of 23 neurologically normal and in only 1 of 22 neurologically abnormal controls. These inclusions, which were present in familial and sporadic ALS cases, and in cases with dementia, took the form of dense rounded or irregular ubiquitin-IR cytoplasmic inclusions (dense bodies), or loosely arranged bundles ('skeins') of filamentous-appearing material. The presence of ubiquitin-IR inclusions corresponded to the pattern of selective neuronal vulnerability in ALS, although inclusions in pyramidal neurons of the motor cortex were infrequent and were noted in only a minority of cases. Ubiquitin-IR inclusions were more prevalent than Bunina bodies. The latter were present in 67% of ALS cases but were seldom labelled by antibodies to ubiquitin. Intraneuronal inclusions resembling Lewy bodies were present in 23% of ALS cases and were often identified by antibodies to ubiquitin. We conclude that the presence of ubiquitin-IR inclusions in lower motor neurons represents a characteristic pathological feature of ALS in its various clinical forms. Ubiquitin-IR inclusions in ALS differ from ubiquitinated inclusions in other neuronal degenerations in that they are not readily identified by antibodies to cytoskeletal proteins. They may represent accumulations of altered or abnormal neuronal proteins resistant to degradation via the ubiquitin proteolytic pathway.
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PMID:Ubiquitin-immunoreactive intraneuronal inclusions in amyotrophic lateral sclerosis. Morphology, distribution, and specificity. 164 64

Chest wall movement and respiratory muscle strength in patients with neuromuscular diseases was studied. Amyotrophic lateral sclerosis, myasthenia gravis and polymyositis were included. Anterior-posterior (AP) and lateral (LT) diameters of the chest wall were measured at the levels of the 2nd and 5th rib, and the abdomen, using 6 pairs of pneumo-magnetometer. Paradoxical movement of LT was often observed in most diseases. Furthermore, both AP and LT of the abdomen showed a paradoxical movement. This paradoxical movement was augmented in resistive loaded breathing and maximum voluntary ventilation. Baseline pulmonary function was minimally disturbed, except for an increase in RV. However, maximum respiratory muscle strength of both inspiratory and expiratory muscles was decreased to approximately 40% of the predicted. This study suggests that neuromuscular diseases may involve the respiratory muscle in the relatively early stage of the disease.
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PMID:[Chest wall mechanics in neuromuscular disease]. 206 47

Activities of cyanide metabolizing enzymes were measured in various subcellular fractions and regions in the central nervous system. Brain rhodanese and liver beta-mercaptopyruvate sulfurtransferase showed a slight decrease in activity after death. The activity of beta-mercaptopyruvate sulfurtransferase was negligible in the rat brain, compared with that of rhodanese. A small amount of thiocyanate was produced from cyanide and beta-mercaptopyruvate in the human brain, probably due to contamination with red blood cells. Rhodanese activity was widely distributed in all the areas of nervous tissue examined. In the rat the olfactory bulb showed the highest rhodanese activity, and high activity was also observed served in the thalamus, septum, hippocampus, and dorsal part of the midbrain. Rhodanese activity was low in various parts of the cerebral cortex. The distribution pattern of rhodanese in post-mortem human brain was essentially similar to that in rat brain. The thalamus, amygdala, centrum semiovale, colliculus superior, and cerebellar cortex showed high rhodanese activity in the human brain. Rhodanese activity was detected in the spinal cord. Anterior horn showed the highest rhodanese activity in the cervical, thoracic, and lumbar cord. Most rhodanese activity in the rat brain was recovered in the mitochondrial fraction with the highest specific activity. Rhodanese activity was lower in spinal cords obtained from autopsied cases with amyotrophic lateral sclerosis than in those of control subjects. A significant decrease in rhodanese was observed in the posterior column of the cervical or thoracic cord, but the activity in the anterior horn did not differ significantly between the two groups.
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PMID:Regional and subcellular distribution of cyanide metabolizing enzymes in the central nervous system. 658 45

Tongue force, rate of syllable repetition, and judgments of articulatory defectiveness were measures obtained on 19 dysarthric adults with amyotrophic lateral sclerosis and on 125 normal adults. Anterior and lateral tongue forces were measured by means of a pressure transducer clasped between the teeth; the tongue forces were recorded on a pen-writing ECG apparatus. Audio-recorded syllable repetitions of /p lambda/, /t lambda/, and /k lambda/ also were transcribed on ECG paper and counted. Three listeners rated articulatory precision on a 7-point scale of severity. The normal males had significantly higher tongue forces than normal females; normal subjects had significantly higher tongue forces than dysarthric patients; and anterior tongue forces were significantly greater than lateral in normal and dysarthric patients. There was a high negative correlation between tongue force and severity of articulatory defect. Syllable repetitions were significantly slower in the dysarthric patients than in the normal patients, and a high negative correlation was obtained between syllabic rate and severity of articulatory defect.
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PMID:Tongue force in normals and in dysarthric patients with amyotrophic lateral sclerosis. 700 62

Two different lines of mice, G1 and G20, carrying a transgene for a mutant form of Cu,Zn SOD, found in a family with familial amyotrophic lateral sclerosis (FALS), develop clinical and pathological changes which are, in their late stages, strikingly similar to those in human disease. We have analyzed the distribution and characteristics of lesions in the central and peripheral nervous systems of such mice. The most affected structure was the spinal cord, followed by the medulla, pons and midbrain. The early stages of the disease were characterized by vascular degeneration of anterior horn neurons and their processes, while, in the late stages, the main changes consisted of neuronal loss and atrophy of the anterior horns and the deposition in these areas of multiple filamentous inclusions resembling Lewy bodies. In the late stages of the disease, the white matter of the spinal cord was also involved, particularly in the anterior and lateral columns. Posterior columns were also involved, but to a much lesser degree. The brainstem structures also showed vacuolar degeneration of several motor nuclei and of several groups neurons in the reticular formation. Anterior roots and peripheral nerves showed the classical features of Wallerian degeneration. The dorsal root ganglia, with rare exceptions, were unremarkable. The posterior roots showed mild changes in the most severely affected mice. Changes in these two affected lines were compared to changes in mice overexpressing wild type, rather than mutant human Cu,Zn SOD. These mice never developed clinical disease, although, pathologically, they developed very mild vacuolar changes in the anterior horns of the spinal cord and in motor axons. This study shows that although simple overexpression of SOD may be injurious to motor neurons, albeit very mildly, the mutant form is necessary to produce both clinical disease and severe pathological changes which, in the chronic stage of the disease, have striking similarities to human familial ALS. A dominant gain of function, therefore, is the most likely pathogenesis of tissue injury induced by mutations in Cu,Zn SOD.
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PMID:Neuropathological changes in two lines of mice carrying a transgene for mutant human Cu,Zn SOD, and in mice overexpressing wild type human SOD: a model of familial amyotrophic lateral sclerosis (FALS). 779 76

Neuronal degeneration in the precentral gyrus alone cannot account for the occurrence of spastic paresis in motor neuron diseases. To look for more extensive cortical atrophy we measured MRIs of the upper parts of the frontal and parietal lobes in 11 sporadic cases of classical amyotrophic lateral sclerosis (ALS), eight patients with primary lateral sclerosis (PLS) and an age- and sex-matched group of 49 neurologically normal people. None of the patients had overt dementia or other mental diseases. In PLS there is progressive spastic paresis but in contrast to ALS there is no lower motor neuron degeneration. The surface area of the precentral gyri and the amount of underlying white matter in PLS were consistently approximately 75% of the normal size. By contrast, there was some shrinkage of the precentral gyri in some of the ALS patients but the mean measurements for the group did not differ significantly from the controls. Anterior to the precentral sulci, the cortical surface area in PLS was approximately 85% of that of the controls, with correspondingly reduced white matter. In ALS the cortical surface areas of the anterior frontal lobes did not differ from those of the controls, but the amount of underlying white matter was reduced almost as much in ALS as it was in PLS. The measured changes in the frontal lobes suggest that in PLS there is simultaneous atrophy of the primary, premotor and supplementary motor areas of the cortex, with consequent degeneration of corticospinal and corticoreticular axons descending through the underlying white matter. These changes could account for the progressive upper motor neuron syndrome. In ALS, with no significant frontal cortical atrophy, the shrinkage of the white matter may be due to degeneration of axons projecting to the frontal cortex from elsewhere. Deprivation of afferents could explain the diminution of motor functions of the frontal lobes in ALS and also the changes in word fluency, judgement and attention that can be detected by appropriate testing in some patients with the disease. Incidental observations include slightly larger parietal lobes but no difference in the frontal lobes in men as compared with women. There was also a small but significant decrease in size of the normal frontal lobes with age. The latter change was much smaller than the atrophy seen in patients with ALS and PLS.
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PMID:Frontal lobe atrophy in motor neuron diseases. 792 62

Insulin-like growth factor-I (IGF-I) is a potent survival factor for motor neurons in animals, and glycogen synthase kinase-3beta (GSK-3beta) is suspected to play roles in apoptosis and tau phosphorylation. Here we report the immunological expression of IGF-I, GSK-3beta, phosphorylated-GSK-3alpha/beta (p-GSK-3alpha/beta) and phosphorylated-tau in the spinal cord and hippocampus of Kii and Guam amyotrophic lateral sclerosis (ALS) patients. Sixteen ALS patients (10 Japanese sporadic, 3 Kii and 3 Guam ALS) and 14 neurological controls (10 Japanese and 4 Guamanian) were examined. The immunoreactivity for each antibody was rated by the percentages of positive neurons to total anterior horn neurons in each patient and was analyzed statistically. Many normal-looking neurons from Japanese sporadic ALS, Kii ALS and Guam ALS patients, as well as from Japanese and Guam controls, were positive for anti-IGF-I antibody. A positive correlation between IR scores for anti-IGF-I antibody and clinical durations of Japanese sporadic ALS patients was found in this study (P < 0.0001). This suggested that IGF-I might have a protective effect against ALS degeneration. In Japanese sporadic ALS patients, abnormal as well as normal-looking neurons showed significant high IR scores for anti-GSK-3beta antibody than those of controls. Anterior horn neurons from Guam and Kii ALS patients characteristically showed weak staining for anti-GSK-3beta antibody but were markedly positive for anti-pGSK-3alpha/beta antibody compared to those from both Japanese controls and Japanese sporadic ALS patients, and showed the co-localization of IGF-I and p-GSK-3alpha/beta. This suggested that the IGF-I signaling pathway in Guam and Kii ALS patients might function to phosphorylate GSK-3beta to protect neurons from ALS degeneration. Neurofibrillary tangles (NFTs) in the hippocampus and spinal cord from Kii and Guam ALS patients showed the co-localization of PHF-tau and p-GSK-3alpha/beta by a confocal laser scanning technique. The predominant expression of p-GSK-3alpha/beta compared to GSK-3beta in spinal motor neurons and the co-localization of p-GSK-3alpha/beta and PHF-tau in NFT-laden neurons in the hippocampus and spinal cord were characteristic findings of Kii and Guam ALS patients.
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PMID:Immunohistochemical expression of IGF-I and GSK in the spinal cord of Kii and Guamanian ALS patients. 1932 91

Cervical spondylosis is common condition rarely associated with radiculomyelopathy which surgical treatment, according to meta-analysis, is not better than nonsurgical. Our hypothesis was that neurodecompression which type is chosen according to spinal alignment should result in better functional improvement comparing with nonsurgical treatment. Between January 1, 1998 and December 31, 2007 a total of 77 patients with spondylogenic myelopathy were selected for the study. The inclusion criteria were symptoms and signs of myelopathy Ranawat grade III. Exclusion criteria were amyotrophic lateral sclerosis (ALS) and multiple sclerosis (MS). The curvature of the cervical spine was determined by Ishihara index. Anterior corpectomies and fusion was performed in the kyphotic spines, laminectomy with fusion in patients with neutral position, and open door laminoplasty in lordotic spines. Clinical improvement was assessed as differences between preoperative and 1-year follow up Nurick, modified Japanese Orthopedic Association (mJOA) myelopathy scales and walking test. Preoperative and postoperative transverse cord area and subarachnoid space were measured. Forty-four male and 31 female patients were surgically treated. Two patients with electrophysiological signs of ALS were excluded. Preoperative and postoperative mean +/- SD mJOA index was 9.15 +/- 1 and 13.01 +/- 1.4 (p < 0.001), Nurick grading scale 3.05 +/- 0.7 and 1.8 +/- 0.6 (p < 0.001), walking time (sec) 64.4 +/- 3.2 and 46.2 +/- 3.3 (p < 0.001), and number of steps 69.7 +/- 4.4 and 57.6 +/- 2.8 (p < 0.001) respectively. Preoperative and postoperative transverse cord area (mean +/- SD, mm2) was 46.7 +/- 5.4 and 60.2 +/- 2.6 (p < 0.001), and subarachnoid space 48.0 +/- 4.9 and 68.8 +/- 8.5 (p < 0.001) respectively. Our results showed that surgical treatment is beneficial for patients with spondylogenic myelopathy.
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PMID:Anterior neurodecompression of kyphotic spondylogenic myelopathy Ranawat grade III and posterior decompression of lordotic spine improve walking ability. 1986 Jan 22

Our objective was to investigate, and establish neuroanatomical correlates of, semantic deficits in amyotrophic lateral sclerosis (ALS) and amyotrophic lateral sclerosis-frontotemporal dementia (ALS-FTD), compared to semantic dementia (SD) and controls. Semantic deficits were evaluated using a naming and semantic knowledge composite score, comprising verbal and non-verbal neuropsychological measures of single-word processing (confrontational naming, comprehension, and semantic association) from the Sydney Language Battery (SYDBAT) and Addenbrooke's Cognitive Examination - Revised (ACE-R). Voxel based morphometry (VBM) analysis was conducted using the region of interest approach. In total, 84 participants were recruited from a multidisciplinary research clinic in Sydney. Participants included 17 patients with ALS, 19 with ALS-FTD, 22 with SD and 26 age- and education-matched healthy controls. Significant semantic deficits were observed in ALS and ALS-FTD compared to controls. The severity of semantic deficits varied across the clinical phenotypes: ALS patients were less impaired than ALS-FTD patients, who in turn were not as impaired as SD patients. Anterior temporal lobe atrophy significantly correlated with semantic deficits. In conclusion, semantic impairment is a feature of ALS and ALS-FTD, and reflects the severity of temporal lobe pathology.
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PMID:Semantic deficits in amyotrophic lateral sclerosis. 2554 44