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)

Two case-control studies of motor neuron disease that involved 712 cases and 158 cases, respectively, showed that (1) mechanical injuries were two to three times more frequent in both sexes, heralding amyotrophic lateral sclerosis, progressive bulbar paralysis, and progressive muscular atrophy; (2) the head, neck, spine, and the extremities were more often traumatized; (3) traumatized parts were not correlated with the initial manifestation of the disease; and (4) more males were traumatized, but males still predominated among uninjured cases. These results suggested that mechanical injuries were not the cause, but probably one of the risk factors of the disease. No association was observed with smoking, drinking, residence, home space, drinking water, animals, experience as a war prisoner, stay on Guam, parental consanguinity, measles, polio, mumps, tuberculosis, rheumatism, prothesis of the total teeth, shell splinters retained in the body, occupational exposures to radiations, chemicals, or gases, atomic bombings, electric injuries, surgical operations, and occupations.
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PMID:Case-control studies of motor neuron disease: association with mechanical injuries. 701 Dec 80

Red blood cell and plasma cholinesterases were evaluated in control subjects and patients with the major forms of adult, sporadic motor neuron disease. For the purposes of this communication, the patients were considered as having amyotrophic lateral sclerosis (ALS) or its subtypes. Cholinesterase and acetylcholinesterase activities were evaluated and separated by dose response to their respective inhibitors. No kinetic differences were observed comparing red blood cell or plasma enzyme activities using either inhibitor. As found in previous studies, acetylcholinesterase accounted for more than 90% of acetylcholine hydrolysis in red blood cells. The plasma data were more complicated to evaluate, but at least 20% of total activity could be attributed to acetylcholinesterase. When red blood cell acetylcholinesterase activities of patients and controls were compared, no statistically significant difference was found. However, when plasma acetylcholinesterase activity was compared between the 2 groups, a statistically significant increase, almost twice the control value, was found in the ALS patients. These data may ultimately be important in the prognosis of this disease and, conceivably, could aid in understanding its pathogenesis.
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PMID:Plasma and red blood cell acetylcholinesterase in amyotrophic lateral sclerosis. 723 44

Thenar motor unit number estimate (MUNE) reproducibility was assessed in 20 patients with amyotrophic lateral sclerosis (ALS) and 16 normal subjects using the multiple point stimulation (MPS) technique. The MUNE was calculated by dividing the thenar compound muscle action potential negative-peak (n-p) area by the mean n-p area of 10 lowest threshold, all-or-nothing, surface-recorded motor unit action potentials. Two trials (test-retest) were performed by the same examiner either on separate days or on the same day with new electrode placements. The mean test MUNE was 43.4 (SD: 35.9, range: 6-145) for ALS patients and 219.4 (SD: 80.8, range: 122-368) for normal subjects. Test-retest MUNE differences were not significant for ALS patients or normal subjects. The test-retest correlation coefficient (r) was 0.99 for ALS patients and 0.85 for normal subjects. The mean difference between test-retest values was 10% for ALS patients and 17% for normal subjects. Test-retest reproducibility of the thenar MUNE using the MPS technique is high in both ALS patients and normal subjects. The reliability of the MPS technique in estimating motor unit numbers may make it a useful outcome measure in following the course of patients with progressive lower motor neuron disease, especially those enrolled in experimental drug trials.
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PMID:Thenar motor unit number estimates using the multiple point stimulation technique: reproducibility studies in ALS patients and normal subjects. 747 64

This report deals with an ultrastructural investigation of the synapses of the proximal axons of normal-appearing anterior horn neurons of 7 patients with amyotrophic lateral sclerosis (ALS) and 4 patients with motor neuron disease who had no upper motor neuron and corticospinal tract involvement (lower motor neuron disease, LMND). Specimens from 12 age-matched individuals who died of non-neurological diseases served as controls. Proximal axons directly emanating from the normal-appearing neurons were examined: 42 axons were from ALS patients, 43 from LMND patients and 87 from controls. Our results show that the number of synapses on axon hillocks, as well as the lengths of the synaptic contact and of the active zone were reduced in both groups of patients (P < 0.0001), but no significant differences were seen between patients and controls with respect to the synaptic parameters of initial axon segments. There was no overall difference between ALS and LMND patients. These findings suggest that the electrophysiological functions pertaining to integration of electrical inputs into the axon and information transduction on the axon may be greatly impaired in the early stages of motor neuron diseases, and that the observed synaptic alterations may be pathological events, likely to be due to anterior horn neuron degeneration.
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PMID:Synaptic loss in the proximal axon of anterior horn neurons in motor neuron disease. 748 93

This report concerns the topographic immunohistochemical analysis of the putamen, globus pallidus (GP) and substantia nigra (SN) of two patients with adult-onset motor neuron disease with basophilic inclusions (MND/BIs), seven patients with sporadic classic amyotrophic lateral sclerosis (sporadic ALS) and five neurologically normal individuals. The striatal efferent terminals of the GP and SN were visualized immunohistochemically using antibodies to met-enkephalin (MEnk) and substance P (SP). In specimens from patients with sporadic ALS and normal subjects there was intense immunostaining for MEnk and SP throughout the external and internal segments of the GP, respectively. By contrast, a marked reduction of MEnk- and SP-positive striatal efferents was seen in the ventrocaudal portions of both GP segments from the MND/BIs patients. Moreover, while MEnk-positive striosomes was readily detected in the putamen of normals and sporadic ALS patients, there was significant reduction in MEnk immunoreactivity, and no evidence of striosomal organization in the putamen of MND/BIs patients. In addition, whereas the SN of patients with sporadic ALS expressed SP, the ventrolateral SN portion of the MND/BIs patient tested had reduced immunoreactivity. The present findings on patients with MND/BIs may represent a reflection of the topographic striatum degeneration in this disease and appear to provide additional evidence for the heterogeneity of MND.
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PMID:Topographic involvement of the striatal efferents in basal ganglia of patients with adult-onset motor neuron disease with basophilic inclusions. 754 58

We discuss the evidence, based on the analysis of transgenic mice overexpressing the human neurofilament (NF) heavy gene, that abnormal NF accumulations can provoke neurodegeneration of motor neurons. Transgenic mice overexpressing by two-fold the normal levels of human NF-H proteins develop a progressive motor neuron disease with several pathologic features reminiscent of those found in amyotrophic lateral sclerosis (ALS). A plausible mechanism for the selective motor neuron degeneration is that exceeding levels of NF-H cross-linkages impede transport of newly synthesized NF structures. The abnormal NF accumulations in perikarya and proximal axons is accompanied by a disruption in axonal transport of not only NF proteins but also of other components required for maintenance of axons. The relevance of the NF-H transgenics as a model of ALS is discussed in light of our current knowledge of motor neuron disease.
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PMID:Mice overexpressing the human neurofilament heavy gene as a model of ALS. 756 55

The influence of a single gene, engineered to be normally or abnormally expressed, can be evaluated in vivo through the development of transgenic animals. Application of this approach in the study of human neurological problems is contributing to an increased understanding of the pathogenic components operative in a variety of disorders. These include Alzheimer's disease, prion encephalopathies, motor neuron disease such as amyotrophic lateral sclerosis, and fragile X syndrome, as well as a number of viral-mediated neurological disorders. These transgenic animals can also serve as models to investigate the possible involvement of additional genetic and environmental factors on the disease state. Moreover, transgenic animals can be used in the development of intervention strategies. The application of this powerful and increasingly popular tool to investigate neurodegenerative disorders is reviewed.
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PMID:Genetically engineered animal models of human neurodegenerative diseases. 758 75

Because of its multi-faceted potential as a neurotrophic factor, insulin-like growth factor I (IGF-I) has been given to hundreds of ALS patients world-wide. Unlike some patients with post-polio syndrome and fragile elderly males, it is unclear whether any of these patients possess disturbances in IGF signaling. We found that about 25% of ALS patients in a controlled trial of human growth hormone (hGH) had lower or higher than normal IGF-I serum levels. Many ALS patients do have some of the characteristics of type II diabetes mellitus, where IGF-I therapy is also under way. In addition, in type I diabetes significant increase in a circulating molecule that binds IGF-I, IGF-I binding protein 1 (IGFBP-1), occurs along with reduced IGF-I, when neuropathic complications are prominent. We have studied the response of IGFBPs in ALS patients to subcutaneous rhIGF-I and found transient induction of IGFBP-1. Studies related to the IGFBPs have not been done in familial ALS (FALS) patients. However, the gene for another IGFBP, BP-2, co-localizes with the gene for juvenile ALS (ALSJ) on chromosome 2. IGF-I has been given to several models of motor neuron degeneration in the mouse, including motor neuron disease and wobbler, with beneficial effects. However, it is also not known whether any accepted genetic mouse model of motor neuron degeneration possesses any disturbance in the IGF signaling system.
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PMID:The insulin-like growth factor signaling system and ALS neurotrophic factor treatment strategies. 759 1

Over 1200 patients with motor neuron disease have been carefully diagnosed, followed, and included in a detailed database delineating characteristics of the disease. Of these patients, 831 were identified as exhibiting typical, sporadic amyotrophic lateral sclerosis (ALS). The progression of the disease in these patients has been followed with our scoring system, and the ALS score was verified as a significant covariate of survival. Age at first symptom, delay from first symptom to entering ALS clinic, and rate of change of respiratory function were also identified as significant covariates of survival. These measures, applied to the Cox proportional hazards model, were used to develop a mathematical model for prediction of survival time in ALS, which proved highly accurate for the 80% of patients at intermediate risk. For those patients, a second model was developed which accurately predicts, after an initial period of observation, the time over which ALS patients will decline a set number of points in total ALS score. Such validation permits initial trials for drug therapies in ALS by comparison of relatively small groups of treated patients to this historical control group, based on the model of predicted time to a particular decrement in total ALS score.
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PMID:Natural history of amyotrophic lateral sclerosis in a database population. Validation of a scoring system and a model for survival prediction. 760 88

Mutations in Cu/Zn superoxide dismutase (SOD1) cause a subset of cases of familial amyotrophic lateral sclerosis. Four lines of mice accumulating one of these mutant proteins (G37R) develop severe, progressive motor neuron disease. At lower levels of mutant accumulation, pathology is restricted to lower motor neurons, whereas higher levels cause more severe abnormalities and affect a variety of other neuronal populations. The most obvious cellular abnormality is the presence in axons and dendrites of membrane-bounded vacuoles, which appear to be derived from degenerating mitochondria. Since multiple lines of mice expressing wild-type human SOD1 at similar and higher levels do not show disease, the disease in mice expressing the G37R mutant SOD1 must arise from the acquisition of an adverse property by the mutant enzyme, rather than elevation or loss of SOD1 activity.
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PMID:An adverse property of a familial ALS-linked SOD1 mutation causes motor neuron disease characterized by vacuolar degeneration of mitochondria. 760 27


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