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)

Nervous system tissues from a number of patients with idiopathic neurological disorders were examined for biochemical evidence of RNA tumor virus infection. RNase-sensitive DNA polymerase activity was found in a cytoplasmic particulate fraction from two patients with Guamanian amyotrophic lateral sclerosis (ALS) but not in brains from two normal U.S. individuals. The buoyant density of the enzyme-containing fraction was 1.16-1.18 g/ml and could be converted to a denser region of the gradient (1.24 g/ml) by treatment with the nonionic surfactant, Sterox. The cation and detergent requirements for the endogenous RNase-sensitive DNA polymerase reaction were determined. The early (5 min) endogenous reverse transcriptase product was analyzed by cesium sulfate gradient centrifugation. RNase- and heat-sensitive RNA-DNA hybrids were detected in the product analysis of two ALS, one Parkinsonism-dementia (PD) brain, and two brains from asymptomatic Chamorros but not in brains from normal U.S. individuals and a number of patients with neuro-psychiatric disorders. The DNA product was a 4.5S heteropolymer that hybridized more extensively to RNA extracted from the enzyme-containing pellet from PD brain as compared to a similar fraction from normal U.S. brain. The DNA product appeared to be unrelated to Rausvher or visna virus 70S RNA as determined by RNA-[-3H]DNA hybridization.
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PMID:RNA-instructed DNA polymerase activity in a cytoplasmic particulate fraction in brains from Guamanian patients. 4 90

The 25,000 dalton protein of Mason-Pfizer monkey virus (MPMV) was isolated by gel filtration chromatography. In agreement with results from other laboratories, antisera to type-C and the non-type-C bovine leukemia and equine infectious anemia viruses did not precipitate 125I-labelled MPMV p25. In addition, these viruses did not cross-react in a competition radioimmunoassay for MPMV p25. Twenty-one human tissues (15 breast carcinomas, 2 normal breasts, 3 acute myelogenous leukemias and 1 sarcoma) were fractionated by detergent solubilization, ammonium sulfate precipitation, and DE-52 anion exchange chromatography. These methods were shown to be highly effective for purification of MPMV p25. Under assay conditions which minimized incubation damage to the 125I-MPMV p25, all tissues failed to react in the competition radioimmunoassay (RIAT). Two hundred and two human sera or plasma specimens, including those from patients with breast cancer and 33 age-matched controls, from 50 patients with hematologic malignancies, from 12 patients with amyotrophic lateral sclerosis, and from 14 patients with systemic lupus erythematosis, were examined for antibodies to MPMV p25. With the exception of two multiple myeloma plasma which produced artifactual false positive reactions based on hypergammaglobulinemia, a known complication of salt precipitation radioimmunoassays, the remainder of the specimens were negative for evidence of MPMV p25 antibodies.
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PMID:Radioimmunoassay for the major structural protein of Mason-Pfizer monkey virus: Attempts to detect the presence of antigen or antibody in humans. 40 48

Recent reports suggest that amyotrophic lateral sclerosis (ALS) is caused by one or more unidentified neurotoxins that are poorly metabolized in patients to less toxic and more readily excreted compounds, and that a genetically determined defect in cysteine degradation and in inorganic sulfate production is the mechanism underlying a failure to metabolize xenobiotics normally in ALS. We measured concentrations of total cysteine and of inorganic sulfate in the plasma of age-matched groups of ALS patients and healthy control subjects and found no differences. L-Cysteine, a putative endogenous neurotoxin in ALS, was present in equal concentrations in autopsied brain from ALS patients and controls.
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PMID:Amyotrophic lateral sclerosis: fasting plasma levels of cysteine and inorganic sulfate are normal, as are brain contents of cysteine. 194 27

The activity of cytochrome P450 family was studied in patients with amyotrophic lateral sclerosis (ALS) in an attempt to evaluate the susceptibility to environmental substances including possible some neurotoxin. The metabolic ratio (MR) of sparteine sulfate was measured in 30 patients with ALS and 41 controls for the evaluation of the sparteine nitro (N)-oxidation with cytochrome P450 system. The population of phenotypes designed as extensive metabolisers (EMs), intermediate metabolisers (IMs), and poor metabolisers (PMs) for sparteine nitro (N)-oxidation was determined in each group. The lower MR (p less than 0.02) and higher frequency of EMs (p less than 0.05) were observed in ALS group, suggesting the excessive activity of N-oxidation with cytochrome P450 pathway in the ALS group. Especially in 15 patients with ALS age before 60, these tendencies were more remarkable with a significant lower MR (p less than 0.01) and extremely high frequency of EMs (p less than 0.005). The present study might suggest the possible participation of cytochrome P450 pathway in the development of ALS.
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PMID:[The excessive activity of cytochrome P450 system in ALS--the metabolic ratio of sparteine]. 260 31

In middle of Kii peninsula, one of the biggest mercury mine in Japan had been present until about 10 years ago. The mercury contents in water and fish are reported to be higher in this district. So we investigated the mercury in hair of patients and normal controls. In this study the subjects are 23 cases of ALS including 15 cases in Nara and Mie and 8 cases in other prefectures except in Kii peninsula, 14 cases with ataxia, 11 cases with other degenerative diseases like Parkinson's disease and Alzheimer's disease, 25 cases of cerebrovascular disease as compared to 26 normal controls. The hair are taken from 3 areas on head of patients and normal controls. They are washed in 2% sodium lauryl sulfate and stirred in distilled water several times, and they are soaked in acetone and dried in filter paper. They are inserted in fire and vaporized mercury are measured (Zeeman Effect Mercury Analyzer) in ppm. The hair mercury concentration is 2.81 ppm in ALS in total, 3.62 ppm in ALS in Nara and Mie and 1.39 ppm in outside of Kii Peninsula, 2.34 ppm in ataxia, 1.83 ppm in other degenerative diseases, 1.66 ppm in cerebrovascular disease and 1.44 ppm in normal controls. Statistically it is significant (p less than 0.05) between that in ALS in Nara and Mie and that in normal controls. 6 cases (40%) with ALS in Nara and Mie have the value above the mean +2 standard deviation of controls.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Mercury in hair of patients with ALS]. 280 5

We studied skin from patients with amyotrophic lateral sclerosis (ALS) and controls by electron microscopy, and analyzed it by sodium dodecyl sulfate-poly-acrylamide gel electrophoresis (SDS-PAGE) and two-dimensional gel electrophoresis. On electron microscopy, the most conspicuous finding in ALS was a markedly increased amount of amorphous material in the ground substance, which became more marked in proportion to the duration of ALS. SDS-PAGE analysis showed that in ALS patients the staining intensity of a low-molecular weight band (approx. 12.5 kDa, band "g") became more marked with the duration of ALS. Two-dimensional gel electrophoresis revealed that band "g" consisted of a single component with a basic isoelectric point. It is thought that the substance corresponding to band "g" is a major constituent of the amorphous material.
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PMID:Amyotrophic lateral sclerosis: electrophoretic study of amorphous material of skin. 233 63

We studied the frequency of oligoclonal immunoglobulin G bands in the cerebrospinal fluid (CSF) of patients with various neurological diseases. We used a micromethod employing sodium dodecyl sulfate polyacrylamide gel electrophoresis that required only 50 microliters of unconcentrated CSF. Oligoclonal bands were detected in the CSF of 95% of the patients with multiple sclerosis, 90% with subacute sclerosing panencephalitis, and 100% with herpes simplex encephalitis, but less frequently in other central nervous system infections. No oligoclonal bands were detected in the CSF of patients with Parkinson, Huntington, Creutzfeldt-Jakob, or herniated disc diseases. Bands were detected in some patients with Alzheimer disease, cerebrovascular accident, idiopathic vertigo, idiopathic seizures, amyotrophic lateral sclerosis, polyneuropathy, and central nervous system glioma. Patients with other conditions infrequently had positive bands. The determination of oligoclonal bands is a useful aid in the diagnosis of multiple sclerosis, subacute sclerosing panencephalitis, and herpes simplex encephalitis. The presence of oligoclonal bands indicates an immunological response but is not diagnostic for a particular condition.
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PMID:Oligoclonal IgG bands in cerebrospinal fluid in various neurological diseases. 683 75

Superoxide dismutases (SODs) scavenge superoxide anion and participate in an essential role as a defense system against oxidative stress in body. Cu,Zn-SOD is localized at cytoplasm. A defect in the Cu,Zn-SOD gene has been demonstrated in some cases of familial amyotrophic lateral sclerosis. Trisomy of chromosome 21 in Down's syndrome increases the level of this isozyme and causes the disease. Inactivation of Cu,Zn-SOD by glycation under hyperglycemic conditions may also be a critical factor for diabetic complication. The expression of the second isozyme, Mn-SOD localized at mitochondrial matrix, is regulated in a complex manner by many stimulants such as interleukin-1, -6, tumor necrosis factor, lipopolysaccharide, and tumor promoters phorbol ester (TPA) and okadaic acid. This isozyme seems to work as a defense mechanism against damage during inflammatory responses. The third isozyme, extracellular SOD, is highly glycosylated and has affinity for heparin sulfate. This may participate in scavenging superoxide in plasma and, therefore, missense mutation in heparin binding domain increases the serum level of this isozyme, although the physiological role is not clearly understood yet.
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PMID:[Physiological significance of superoxide dismutase isozymes]. 760 83

Apoptotic cell death has recently been implicated in diseases involving nonproliferating, terminally differentiated cells such as neurons. Previous experiments have documented that immunoglobulins from patients with amyotrophic lateral sclerosis (ALS) can kill motoneuron-neuroblastoma hybrid cells [ventral spinal cord 4.1 (VSC 4.1)] by a calcium-dependent process. Here, we studied the mechanism of ALS IgG-induced cell death. In the presence of ALS IgG the VSC 4.1 cells undergo cell shrinkage and membrane blebbing, which are morphological features of apoptotic cell death. The damaged cells can be identified by in situ end labeling of nicked DNA and biochemically show laddering on agarose gel electrophoresis. This ALS IgG-triggered process is prevented by cycloheximide, aurintricarboxylic acid, and zinc sulfate. These data demonstrate that immunoglobulins from patients with ALS are able to induce apoptosis in motoneuron hybrid cells and provide a potential mechanism for motoneuron degeneration in human ALS.
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PMID:Apoptotic cell death of a hybrid motoneuron cell line induced by immunoglobulins from patients with amyotrophic lateral sclerosis. 796 60

Neurofibrillary tangles (NFT), one of the neurodegenerative features of Alzheimer's disease, Down's syndrome and normal aging, is a constant, widespread neuropathological finding in Guamanian amyotrophic lateral sclerosis (ALS), parkinsonism-dementia (PD) and in neurologically normal Guamanians, dying of causes other than ALS and PD. NFT in brain tissue sections of patients with Guamanian ALS and PD were immunoreactive to antibodies directed against a 43-amino acid synthetic peptide homologous to amyloid beta/A4-protein (anti-SP43) associated with Alzheimer's disease. NFT extracted from frozen brain tissues of Guamanian patients with ALS and PD and from tissues of neurologically normal Guamanians were congophilic and birefringent. By negative-stain electron microscopy, NFT preparations contained bundles and/or isolated single, straight, unpaired filaments in Guamanian ALS and occasionally pairing of filaments in neurologically normal Guamanians, measuring 5-20 nm in diameter. Formic acid digestion of NFT preparations, followed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and size-exclusion high-pressure liquid chromatography, showed a protein with an apparent molecular mass of 4- to 4.5-kDa, which by Western blot analysis was immunoreactive to anti-SP43. Immunoabsorption of purified NFT or SP43 with anti-SP43 abolished immunostaining. Our study corroborate previous data that amyloid beta/A4-protein is present in NFT in Guamanian PD. Furthermore, our data indicate that amyloid beta/A4-protein is present in NFT in brain tissues of patients with Guamanian ALS and in neurologically normal Guamanians, suggesting a common mechanism of amyloidogenesis with NFT formation in Alzheimer's disease and normal brain aging.
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PMID:Neurofibrillary tangles of Guamanian amyotrophic lateral sclerosis, parkinsonism-dementia and neurologically normal Guamanians contain a 4- to 4.5-kilodalton protein which is immunoreactive to anti-amyloid beta/A4-protein antibodies. 821 85


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