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

Chronic dietary deficiency of calcium (Ca) and magnesium (Mg) with excessive intake of aluminum (Al) and manganese (Mn) has been implicated in the pathogenesis of high incidence amyotrophic lateral sclerosis (ALS) in the Western Pacific. We report two cases of ALS from the Kii Peninsula of Japan with markedly elevated concentrations of Al in central nervous system (CNS) tissues. Six pathologically verified cases of ALS and five neurologically normal controls were studied. Levels of Al, Ca and phosphorus (P) were determined simultaneously by neutron activation analysis (NAA), and Mg concentration was measured by inductively coupled plasma emission spectrometry (ICP) in 26 CNS regions. Al concentrations in the precentral gyrus, internal capsule, crus cerebri and spinal cord were significantly increased in two ALS patients, compared with those of controls. Mean Al concentrations of the 26 CNS regions in these two patients were also higher than those of controls and of the four other ALS cases (p less than 0.01). By contrast, Mg concentrations in the 26 CNS regions were markedly reduced in the ALS cases, compared with controls (p less than 0.01), and the Ca/Mg ratios were significantly increased in the ALS cases (p less than 0.01). Our data indicate that high-incidence ALS in the Western Pacific may result from Ca-Mg dysmetabolism with resultant deposition of Al.
 ...
PMID:Aluminum deposition in the central nervous system of patients with amyotrophic lateral sclerosis from the Kii Peninsula of Japan. 174 44

Recent decline in incidence rates of ALS in Guam and the Kii Peninsula of Japan strongly implicates environmental factors rather than inheritance in its causation. Environmental studies in Western Pacific foci showed identical mineral compositions in the soils and drinking water, i.e., extremely low calcium (Ca) and magnesium (Mg) and high aluminum (Al) and manganese (Mn). Series of trace-elemental analyses of the CNS tissue of ALS patients have revealed a high contents of Al and Ca with significant positive correlations between Al and Ca and/or between Ca and Mn, suggesting the prolonged exposure to these trace environment to cause abnormal mineral metabolism detrimental to neurons. Using electron energy loss spectrometry (EELS), Al was found to accumulate within DNA-containing chromatins and rRNA-containing cellular components, i.e., nucleolus, heterochromatin, rough endoplasmic reticulum, in lumbar motor neurons of ALS. Thus, Al may preferentially bind to nucleic acids and cause a progressive inhibition of the protein synthesis of rRNA and the transcription or gene modulation of DNA, leading to neuronal degeneration.
 ...
PMID:[Environmental factors in western Pacific foci of ALS and a possible pathogenetic role of aluminum (Al) in motor neuron degeneration]. 181 96

Continuing analytical studies on environmental factors in the foci of amyotrophic lateral sclerosis (ALS) in the Kii Peninsula of Japan and Guam, and metal analysis using neutron activation analysis in central nervous system (CNS) tissues from ALS cases indicate that chronic exposure to metals such as aluminum and manganese, together with a deficiency of minerals such as calcium and magnesium, may play a causative role in the neurodegeneration seen in ALS. An accurate and simple method for detecting minerals and trace metals in small, fresh samples of CNS tissue is necessary in order to follow the pathogenetic behavior of these elements. In this paper, we describe a method for measuring manganese (Mn) content in CNS tissue samples taken from mouse brain using inductively coupled plasma (ICP) spectroscopy and present results of the determination of Mn contents in spinal cord samples from ALS cases using the same method. ICP emission spectroscopy is considered to have great advantage for the simultaneous determination of elements in small, fresh CNS samples because of its simplicity and convenience, and the elimination of the necessity to use potentially dangerous acids. Results showed that the mean concentration of Mn in a mouse brain (0.56 microgram/g) and in human spinal cords (0.39 microgram/g wet weight in the anterior horn, 0.37 in the lateral fasciculus, 0.39 in the posterior horn and 0.28 in the posterior fasciculus) were compatible with results previously reported using other methods. In ALS spinal cords, the mean content of Mn was similar to that of controls, but the distribution differed. In the ALS cases, Mn contents were higher in the anterior horn and lateral fasciculus than in the posterior horn.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Determination of manganese concentrations in the spinal cords from amyotrophic lateral sclerosis patients by inductively coupled plasma emission spectroscopy. 224 33

Long-term epidemiological studies indicate that environmental factors play a causative role in high-incidence amyotrophic lateral sclerosis (ALS) and parkinsonism-dementia (PD) in the western Pacific. An increased risk for disease is acquired in youth and remains for life. The low concentrations of calcium and magnesium and high levels of aluminum in the soil and drinking water, along with the relative isolation of these populations, constitute an unusual environmental feature common to all three high-incidence foci. Studies of mineral deposition in brain tissue of Guamanian ALS and PD patients, as well as of neurologically normal Guamanians with neurofibrillary degeneration, demonstrate accumulations of calcium, aluminum and silicon in neurofibrillary tangle-bearing neurons. In an attempt to duplicate the low calcium and high aluminum and manganese in soil and drinking water in these foci, we maintained juvenile cynomolgus monkeys for 41 to 46 months on a low-calcium diet with or without supplemental aluminum and manganese. Experimental animals exhibited mild calcium and aluminum deposition and degenerative changes, compatible with those of early ALS and PD, in motor neurons of the spinal cord, brain stem, substantia nigra and cerebrum. Neuropathological findings included chromatolysis, aberrant perikaryal accumulation of phosphorylated neurofilament, neurofibrillary tangles, axonal spheroids, and basophilic and hyaline-like inclusions consisting of abnormal cytoskeletal elements by electron microscopy. The magnitude and extent of these lesions far exceeded those found in normal aged monkeys.
 ...
PMID:Low-calcium, high-aluminum diet-induced motor neuron pathology in cynomolgus monkeys. 275 Apr 90

A retrospective case-control study of occupational heavy metal exposure was conducted using 66 amyotrophic lateral sclerosis (ALS) patients and 66 age- and sex-matched controls. Cases were ascertained primarily through a neurology support and research clinic. The self-administered questionnaire probed potential exposure to nine heavy metals: aluminum, lead, lead alkyl, magnesium, manganese, mercury, mercury alkyl, nickel and selenium. Using McNemar's test and a Mantel Haenszel extended analysis, no association was found between heavy metal exposure and the pathogenesis of ALS in this patient population. Demographic factors, fracture history, immunizations, travel and other variables were similar in ALS patients and controls.
 ...
PMID:Amyotrophic lateral sclerosis and occupational heavy metal exposure: a case-control study. 374 67

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.
 ...
PMID:Heavy metal concentrations in blood cells in patients with amyotrophic lateral sclerosis. 398 Dec 18

The manganese distribution in the cross-section of the cervical, thoracic and lumbar portion of the spinal cords from 7 autopsied cases with amyotrophic lateral sclerosis (ALS) and 6 control subjects were determined by radiochemical neutron activation analysis. It was possible to determine 1 ng levels of manganese content accurately in the small tissues about 1 mg of dried weight using wet ashing and chemical separation after neutron activation. The dried weight of spinal cord was about 1/3 of the wet weight. Manganese concentration in the wet tissue was calculated from the ratio of dried to wet weight. In the anterior horn of the cervical cords of ALS, manganese concentration was the highest; 1.75 +/- 0.39 ng/mg of dried weight and 0.59 +/- 0.09 ng/mg of wet weight, respectively. These were significantly higher (P less than 0.01) compared to those in controls; 1.02 +/- 0.12 ng/mg of dried weight and 0.35 +/- 0.04 ng/mg of wet weight, respectively. The elevation of manganese level in the spinal cords of ALS was more prominent in the anterior horn and lateral column than in the posterior column both in dried and wet tissues. Since manganese inhibits neuronal transmission, it is likely that neurological degenerative changes occur as a result of local disturbances of manganese metabolism in the spinal cord of ALS.
 ...
PMID:Increased manganese level in spinal cords of amyotrophic lateral sclerosis determined by radiochemical neutron activation analysis. 664 29

Ca/P atomic ratios in spinal cords of seven amyotrophic lateral sclerosis (ALS) cases were determined by neutron activation and X-ray fluorescence analyses, and were compared with those of seven control cases. In order to obtain calibration curves, the standard samples with 0.01-0.1 of Ca/P atomic ratio were prepared by mixing diammonium hydrogen phosphate with calcium carbonate. In neutron activation analysis, gamma-ray spectra of 49Ca and beta-ray intensities of 32P produced from (n, gamma) reactions of the spinal cords and standard samples were measured by Ge(Li) and GM detectors, respectively. In X-ray fluorescence analysis, the samples were excited with 1.6 MeV alpha particle beam accelerated by a Van de Graaff accelerator, manganese K X-rays from 55Fe radioactive source and rhodium K alpha X-rays from X-ray tube, respectively. The characteristic X-ray spectra were measured by Si(Li) or proportional detector. From the peak areas on the spectra and beta-ray intensities, the Ca/P atomic ratios in spinal cords were determined. Based on these results, the Ca/P atomic ratio of precipitate including calcium and phosphorus in spinal cord of ALS case was calculated. As a result, the Ca/P atomic ratios in spinal cords of ALS and control cases were 0.018-0.021 and 0.030-0.049, respectively. The calculated Ca/P atomic ratio in the precipitate of ALS case was estimated to be 1.6.
 ...
PMID:[Determination of the Ca/P atomic ratio in the spinal cord of patients with amyotrophic lateral sclerosis by neutron activation and X-ray fluorescence analysis]. 667 59

The concentrations of arsenic, manganese and selenium/g wet tissue weight were determined in samples from 24 areas of the human brain from 3 patients with chronic renal insufficiency, 2 with Parkinson's disease and 1 with amyotrophic lateral sclerosis. The concentrations of the 3 elements were determined for each sample by neutron activation analysis with radiochemical separation. Overall arsenic concentrations were about 2.5 times higher in patients with chronic renal failure than in controls, and lower than normal in the patients with Parkinson's disease and amyotrophic lateral sclerosis. There were no obvious differences in the overall concentrations of manganese and selenium from one group to another. Even multivariate data analysis by the SIMCA method failed to reveal any significant difference in the distribution pattern of manganese and selenium in Parkinson's disease compared to normal controls.
 ...
PMID:Distribution of arsenic, manganese, and selenium in the human brain in chronic renal insufficiency, Parkinson's disease, and amyotrophic lateral sclerosis. 727 87

Metal analysis of calcium, manganese, aluminum and copper in CNS tissue samples of degenerative CNS disease cases (six Japanese ALS, three Japanese Alzheimer disease, four Guam PD, one Guam ALS) using neutron activation analysis, was conducted with following results: Five of six Japanese ALS cases, two of three Japanese Alzheimer disease cases and all of four Guam PD cases showed a high content of calcium and aluminum in CNS tissue with a significant positive correlation between calcium and aluminum and/or between calcium and manganese. These findings suggest a possible process of metal-induced soft tissue calcification with interaction of other di- and/or trivalent cations such as aluminum, manganese in CNS tissue of these degenerative CNS diseases.
 ...
PMID:Studies on amyotrophic lateral sclerosis by neutron activation analysis--2. Comparative study of analytical results on Guam PD, Japanese ALS and Alzheimer disease cases. 739 Mar 31


1 2 3 4 5 6 7 Next >>