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)

Magnetic resonance imaging (MR imaging) provides a sensitive method for mapping the normal and pathological distribution of iron in the brain. High field strength MR imaging (1.5 T) was used to evaluate eight patients with amyotrophic lateral sclerosis (ALS) and 49 neurological normal control patients. All eight ALS patients showed decreased signal intensity in the motor cortex on T2-weighted images, while only one of the normal control patients showed this finding. The results suggested that the decreased signal intensity in the motor cortex in ALS was caused by the deposition of iron in this area.
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PMID:[MR imaging of amyotrophic lateral sclerosis]. 163 Aug 88

The possible role of trace elements in a pathogenesis of central nervous system (CNS) on degenerative and demyelinating diseases has been suggested. Simultaneous measurements of Zinc (Zn) and iron (Fe) concentration in CNS were undertaken by neutron activation analysis in CNS tissues: a patient with multiple sclerosis (MS), five patients with amyotrophic lateral sclerosis (ALS), five with spinocerebellar degeneration (SCD), and five with cerebral infarction (CVD) in non-invasive area of CNS as control. Although Zn and Fe concentration were present in white matter and gray matter of CNS in each disease, 1) Zn concentration showed no special pattern in gray matter among four diseases, but decreased more in white matter of MS and ALS than that of CVD (p less than 0.05); 2) Fe concentration in gray matter of SCD increased more than that in CVD (p less than 0.05), but Fe concentration in white matter of CVD was increased more than that of ALS (p less than 0.05); 3) Fe concentration of CNS in a patient with MS was not notable except for high Fe concentration in caudate nucleus and globus pallidus. The demyelinated pathological area in CNS of MS showed a decrease in Zn level but no change in Fe level. These results indicate that low Zn concentration in CNS tissues of MS seemed to be responsible for CNS demyelination, but not for undernutrition due to poor conditions of a patient with MS. It seems that Zn might be one pathogenetic factor of MS, but the action of Fe in MS can not be ruled out.
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PMID:[Zinc concentration in the central nervous system in a case of multiple sclerosis--comparison with other neurological diseases]. 179 99

The toxicity of aluminum in plant and animal cell biology is well established, although poorly understood. Several recent studies have identified aluminum as a potential, although highly controversial, contributory factor in the pathology of Alzheimer disease, amyotrophic lateral sclerosis, and dialysis dementia. For example, aluminum has been found in high concentrations in senile plaques and neurofibrillary tangles, which occur in the brains of subjects with Alzheimer disease. However, a mechanism for the entry of aluminum (Al3+) into the cells of the central nervous system (CNS) has yet to be found. Here we describe a possible route of entry for aluminum into the cells of the CNS via the same high-affinity receptor-ligand system that has been postulated for iron (Fe3+) delivery to neurons and glial cells. These results suggest that aluminum is able to gain access to the central nervous system under normal physiological conditions. Furthermore, these data suggest that the interaction between transferrin and its receptor may function as a general metal ion regulatory system in the CNS, extending beyond its postulated role in iron regulation.
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PMID:Aluminum access to the brain: a role for transferrin and its receptor. 224 78

Manganese (Mn) and selenium (Se) concentrations in blood cells were measured by neutron activation analysis. Blood was obtained from patients with amyotrophic lateral sclerosis (ALS), patients with other neurological diseases and control subjects. Dried blood cells were activated by neutron irradiation. Mn was determined after chemical separation and Se was determined nondestructively. Mn concentrations in blood cells from ALS patients were significantly lower (P less than 0.01) than those from the other groups. The Mn concentrations were also significantly lower (P less than 0.01) in late than in earlier stages of ALS. Se concentrations in blood cells from ALS patients were significantly higher (P less than 0.01) than those from the other two groups. A generalized abnormal distribution of these metals may play a role in the pathogenesis of this disorder. Bromine, zinc, rubidium, and iron concentrations of erythrocytes were the same in all groups.
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PMID:Heavy metal concentrations in blood cells in patients with amyotrophic lateral sclerosis. 398 Dec 18

The in vivo generation of .OH free radicals in specific brain regions can be measured by intracerebral microdialysis perfusion of salicylate, avoiding many of the pitfalls inherent in systemic administration of salicylate. Direct infusion of salicylate into the brain can minimize the hepatic hydroxylation of salicylate and its contribution to brain levels of 2,5-DHBA. Levels of 2,5-DHBA detected in the brain dialysate may reflect the .OH adduct plus some enzymatic hydroxylation of salicylate in the brain. After minimizing the contribution of enzyme and/or blood-borne 2,5-DHBA, the present data demonstrate the validity of the use of 2,3-DHBA and apparently 2,5-DHBA as indices of .OH formation in the brain. Therefore, intracranial microdialysis of salicylic acid and measurement of 2,3-DHBA appears to be a useful .OH trapping procedure for monitoring the time course of .OH generation in the extracellular fluid of the brain. These results indicate that nonenzymatic and/or enzymatic oxidation of the dopamine released by MPTP analogues in the extracellular fluid may play a key role in the generation of .OH free radicals in the iron-rich basal ganglia. Moreover, a site-specific generation of cytotoxic .OH free radicals and quinone/semiquinone radicals in the striatum may cause the observed lipid peroxidation, calcium overload, and retrograde degeneration of nigrostriatal neurons. This free-radical-induced nigral injury can be suppressed by antioxidants (i.e., U-78517F, DMSO, and deprenyl) and possibly hypothermia as well. In the future, this in vivo detection of .OH generation may be useful in answering some of the fundamental questions concerning the relevance of oxidants and antioxidants in neurodegenerative disorders during aging. It could also pave the way for the research and development of novel neuroprotective antioxidants and strategies for the early or preventive treatment of neurodegenerative disorders, such as Parkinson's disease (Wu et al., this issue), amyotrophic lateral sclerosis, head trauma, and possibly Alzheimer's cognitive dysfunction as well. In conclusion, this in vivo free-radical trapping procedure provides evidence to support a current working hypothesis that a site-specific formation of cytotoxic .OH free radicals in the basal ganglia may be one of the neurotoxic mechanisms underlying nigrostriatal degeneration and Parkinsonism caused by the dopaminergic neurotoxin MPTP. Addendum added in proof: The controversy concerning possible neurotoxic and/or neuroprotective roles of NO. in cell cultures was discussed and debated at the symposium (Wink et al., this issue; Dawson et al., this issue; Lipton et al., this issue).(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:In vivo generation of hydroxyl radicals and MPTP-induced dopaminergic toxicity in the basal ganglia. 783 34

Lactotransferrin is a glycoprotein that specifically binds and transports iron. This protein is also believed to transport other metals such as aluminum. Several lines of evidence indicate that iron and aluminum are involved in the pathogenesis of many dementing diseases. In this context, the analysis of the iron-binding protein distribution in the brains of patients affected by neurodegenerative disorders is of particular interest. In the present study, the distribution of lactotransferrin was analyzed by immunohistochemistry in the cerebral cortex from patients presenting with Alzheimer's disease, Down syndrome, amyotrophic lateral sclerosis/parkinsonism-dementia complex of Guam, sporadic amyotrophic lateral sclerosis, or Pick's disease. The results show that lactotransferrin accumulates in the characteristic lesions of the different pathologic conditions investigated. For instance, in Alzheimer's disease and Guamanian cases, a subpopulation of neurofibrillary tangles was intensely labeled in the hippocampal formation and inferior temporal cortex. Senile plaques and Pick bodies were also consistently labeled. These staining patterns were comparable to those obtained with antibodies to the microtubule-associated protein tau and the amyloid beta A4 protein, although generally fewer neurofibrillary tangles were positive for lactotransferrin than for tau protein. Neuronal cytoplasmic staining with lactotransferrin antibodies, was observed in a subpopulation of pyramidal neurons in normal aging, and was more pronounced in Alzheimer's disease, Guamanian cases, Pick's disease, and particularly in Down syndrome. Lactotransferrin was also strongly associated with Betz cells and other motoneurons in the primary motor cortex of control, Alzheimer's disease, Down syndrome, Guamanian and Pick's disease cases. These same lactotransferrin-immunoreactive motoneurons were severely affected in the cases with amyotrophic lateral sclerosis. It is possible that in these neurodegenerative disorders affected neurons either take up or synthesize lactotransferrin to an abnormally elevated rate. An excessive accumulation of lactotransferrin, as well as transported iron and aluminum, may lead to a cytotoxic effect resulting in the formation of intracellular lesions and neuronal death.
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PMID:The iron-binding protein lactotransferrin is present in pathologic lesions in a variety of neurodegenerative disorders: a comparative immunohistochemical analysis. 795 73

Oxidative DNA damage can cause mutation and cell death. We show that L-DOPA, dopamine and 3-O-methyl-DOPA cause extensive oxidative DNA damage in the presence of H2O2 and traces of copper ions. 8-Hydroxyguanine is the major product. Iron ions were much less effective and manganese ions did not catalyse DNA damage. We propose that copper ion release, in the presence of L-DOPA and its metabolites, may be an important mechanism of neurotoxicity, e.g. in Parkinson's disease and amyotrophic lateral sclerosis.
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PMID:Intense oxidative DNA damage promoted by L-dopa and its metabolites. Implications for neurodegenerative disease. 795 67

We performed morphologic studies on skin from seven patients with ALS and seven control subjects. By light microscopy, the wide spaces that separated collagen bundles reacted strongly with colloidal iron and alcian blue in ALS patients. Electron microscopy revealed markedly increased amorphous material that was positive for ruthenium red in the ground substance. These findings were not present in controls. Quantitative amino acid analysis showed that the amount of total amino acids (nmoles per mg dry weight) was significantly decreased (p < 0.01) in ALS patients compared with that of controls, and there was a significant negative correlation between skin amino acid content and duration of illness in ALS patients (r = -0.83, p < 0.001). These morphologic findings and biochemical data indicate that the amorphous material, which is markedly increased in ALS skin, includes glycosaminoglycans.
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PMID:Amorphous material of the skin in amyotrophic lateral sclerosis: a morphologic and biochemical study. 814 27

Simultaneous measurements of zinc (Zn) and iron (Fe) concentrations were determined using neutron activation analysis in gray and white matter of the frontal and occipital regions obtained from four patients with parkinsonism-dementia (PD), eight with amyotrophic lateral sclerosis (ALS), and four neurologically normal controls from Guam. Zn content in gray matter from the frontal cortex in ALS and PD cases was significantly decreased, compared with that of controls (p < 0.05). No significant differences were found in the Zn content of white matter from the frontal cortex, and/or gray and white matter from the occipital cortex between the groups. The Zn content in gray matter from both frontal and occipital regions was less in ALS and PD patients than in controls. Fe content in gray matter from the frontal cortex of ALS and PD increased significantly compared with that of controls (p < 0.05). Fe content in white matter from the frontal cortex in PD patients was greater than in controls (p < 0.05), with an overall difference: controls < ALS < PD. These data indicate that an increase in Fe in gray and white matter, and a decrease concentration of Zn in gray matter, combined with an excess and deficiency of bioavailable aluminum and calcium, respectively, may be involved in the pathogenic process of these disorders.
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PMID:Concentrations of zinc and iron in the brains of Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia. 816 89

We measured aluminum (Al), calcium (Ca), and iron (Fe) levels in neuronal cytoplasm and nucleus, capillaries, and neuropil in samples of ventral cervical spinal cord from 5 patients with sporadic amyotrophic lateral sclerosis (ALS) and 5 age-matched controls using laser microprobe mass spectrometry (LMMS). The concentration of Al was not altered in any area in the ALS samples. In contrast, Fe and Ca were increased 1.5-2-fold in the nucleus and cytoplasm of ALS neurons but not in capillaries and neuropil. These findings do not support the hypothesis that Al is enriched in spinal cord of sporadic ALS as has been reported for Guamanian ALS/Parkinson's dementia. The elevations of Fe in spinal neurons are consistent with reports of increased Fe in bulk samples of ALS spinal cord. The presence of increased Fe within spinal neurons may be significant in the pathogenesis of motor neuron degeneration by catalyzing the generation of reactive oxygen species within specific cells.
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PMID:Aluminum, calcium, and iron in the spinal cord of patients with sporadic amyotrophic lateral sclerosis using laser microprobe mass spectroscopy: a preliminary study. 858 87


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