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)

Connectin (also called titin) is a myofibrillar elastic filament which links a thick filament to a neighbouring Z line in a sarcomere and thus contributes significantly to the elasticity of myofibrils. In a previous study, we demonstrated by Western blot analysis of the biopsied skeletal muscles using an anti-connectin monoclonal antibody that connectin was degraded extensively after 5 years of age in Duchenne muscular dystrophy (DMD), while it was degraded mildly in Becker muscular dystrophy and only minimally in myotonic dystrophy, limb girdle dystrophy, amyotrophic lateral sclerosis and Charcot-Marie-Tooth disease. In the present study, we investigated the degradation state of connectin in Fukuyama type congenital muscular dystrophy (FCMD) by a similar method using 2 distinct anti-connectin monoclonal antibodies. In FCMD, connectin degradation began much earlier than in DMD: Definite degradation was already observed in 5-8-month-old patients. It was presumed that connectin degradation would play an important role in the myofibrillar degeneration in the early stage of FCMD.
J Neurol Sci 1990 Sep
PMID:Degradation of connectin (titin) in Fukuyama type congenital muscular dystrophy: immunochemical study with monoclonal antibodies. 224 26

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)
J Neurol Sci 1990 Sep
PMID:Determination of manganese concentrations in the spinal cords from amyotrophic lateral sclerosis patients by inductively coupled plasma emission spectroscopy. 224 33

We subjected cerebrospinal fluid (CSF) samples from over 200 patients with various neurological diseases to two-dimensional electrophoresis. The series included non-inflammatory diseases such as epilepsy, amyotrophic lateral sclerosis, and polyneuropathy; and inflammatory diseases such as multiple sclerosis and neurolues. In the resulting electrophoretograms we considered mainly the region of CSF-specific proteins and the area corresponding to the immunoglobulin light chains. The former, at Mr 35 000-38 000, shows some interesting variations from one CSF to another. Samples from patients with various brain tumors show a specific change. A zone of oligoclonal immunoglobulin light chains appeared in all CSF samples with above-normal gamma-globulin content. These oligoclonal patterns remained constant and characteristic during the course of different diseases for several patients so examined. As expected, differences appeared in the patterns of immunoglobulin light chains from one individual to another, even among a group of patients with the same disease. The extent of the correlation of certain basic patterns with certain diseases cannot yet be determined.
Clin Chem 1985 Sep
PMID:Two-dimensional gel electrophoresis of cerebrospinal fluid proteins from patients with various neurological diseases. 241 49

We investigated the epitope specificity of monoclonal antibodies (M-proteins) from two patients with motor neuron disease and IgM monoclonal gammopathy. In previous studies, both M-proteins bound to gangliosides GM1 and GD1b which share Gal(beta 1-3)GalNAc as their terminal structure, and to lacto-N-tetraose-BSA which has the structure Gal(beta 1-3)GlcNAc(beta 1-3)Gal(beta 1-4)Glc-BSA. In this study we show that the serum IgM from both patients bind to bovine serum albumin (BSA) glycoconjugates of both Gal(beta 1-3)GalNAc and Gal(beta 1-3)GlcNAc. Binding was detected at serum dilutions of up to 1:100,000, and absorption with Gal(beta 1-3)GlcNAc-BSA completely removed the IgM binding to Gal(beta 1-3)-GalNAc-BSA, indicating that the same antibodies bound to both epitopes. Low levels of antibodies to Gal(beta 1-3)GlcNAc-BSA and to Gal(beta 1-3)GlcNAc-BSA were also detected in patients with amyotrophic lateral sclerosis (ALS) and in normal subjects at serum dilutions of up to 1:500, but these did not have the same specificity as the M-proteins, as binding to Gal(beta 1-3)GalNAc-BSA was not inhibited by absorption with Gal(beta 1-3)GlcNAc-BSA.
J Neuroimmunol 1988 Sep
PMID:Monoclonal IgM in two patients with motor neuron disease bind to the carbohydrate antigens Gal(beta 1-3)GalNAc and Gal(beta 1-3)GlcNAc. 245 3

Recent studies have implicated the ingestion of the structurally related plant excitotoxins, beta-N-methylamino-L-alanine (BMAA), and beta-N-oxalylamino-L-alanine (BOAA), in the pathogenesis of two human motor system diseases, the amyotrophic lateral sclerosis-Parkinsonism-dementia complex of Guam (Guam ALS-PD), and lathyrism, respectively. We have investigated the toxicity of these amino acids on cultured mouse cortical neurons in the presence of physiological concentrations of bicarbonate (a required toxic cofactor for BMAA neurotoxicity). A 24 h exposure to 10 microM - 3 mM BMAA, or to 300 nM - 100 microM BOAA, induced, concentration-dependent neuronal degeneration without glial damage; the neurotoxic EC50 for BMAA was about 1 mM, and the EC50 for BOAA was about 20 microM. At high concentrations, both compounds destroyed essentially the entire neuronal population. Neurotoxicity also depended on exposure duration, with reduced injury at an exposure time of 1 h, and increased injury at an exposure time of 3 days. Despite the fact that ingestion of BMAA and BOAA both lead to motor system damage, previous studies have suggested that the two excitotoxins act primarily on different glutamate receptor subtypes: BMAA on N-methyl-D-aspartate (NMDA) receptors, and BOAA on non-NMDA receptors. Consistent with these studies, the neurotoxicity of high concentrations of BMAA was substantially attenuated by 1 mM D-amino-5-phosphonovalerate (D-APV), whereas BOAA neurotoxicity was less sensitive to D-APV but was attenuated by 2 mM kynurenate.(ABSTRACT TRUNCATED AT 250 WORDS)
Brain Res 1989 Sep 11
PMID:Neurotoxicity of beta-N-methylamino-L-alanine (BMAA) and beta-N-oxalylamino-L-alanine (BOAA) on cultured cortical neurons. 255 52

beta-N-methylamino-L-alanine (BMAA) is a neurotoxic glutamate agonist possibly responsible for the neuronal degeneration found in the Guam amyotrophic lateral sclerosis-Parkinsonism-dementia complex. The basis for glutamate receptor activation by BMAA has been unclear, as BMAA lacks the omega electronegative moiety characteristic of other excitatory amino acids. We recently reported that the neuroexcitatory and neurotoxic effects of BMAA depend strongly on the presence of bicarbonate ions and proposed that an interaction between bicarbonate and the beta amino group of BMAA produces a molecular configuration appropriate for activating glutamate receptors. We now report that bicarbonate potentiates the ability of BMAA to open NMDA receptor-activated channels in isolated membrane patches. Furthermore, the neurotoxic and neuroexcitatory effects of two structural analogs of BMAA, DL-2,4-diaminobutyrate and DL-2,3-diaminopropionate, were also potentiated by bicarbonate. These findings support the bicarbonate cofactor hypothesis for BMAA action and provide direct evidence that it may be generalizable to certain other compounds.
Neuron 1989 Sep
PMID:Bicarbonate dependence of glutamate receptor activation by beta-N-methylamino-L-alanine: channel recording and study with related compounds. 256 69

We studied trophic effects of angiotensin II, vasopressin and oxytocin on explanted ventral spinal cord cultures from 13-14-old day rat embryos. There was a significant neurite promoting effect in angiotensin II and vasopressin-treated cultures. Angiotensin II had the most potent effect at any concentrations. It became clear that minimum effective concentration was 10(-8) M in angiotensin II and vasopressin respectively. Effect of these two neuropeptides was concentration-dependent. However, oxytocin had no neurotrophic effect at any concentrations. Our results demonstrated that angiotensin II and vasopressin have a neurotrophic effect on ventral spinal cord in cultures, and may contribute to therapeutic strategy of amyotrophic lateral sclerosis.
Int J Neurosci 1989 Sep
PMID:Neurotrophic effect of angiotensin II, vasopressin and oxytocin on the ventral spinal cord of rat embryo. 258 29

A 64-year-old male patient of amyotrophic lateral sclerosis (ALS) with frozen gait, axial rigidity and supranuclear upper gaze palsy was reported. We have followed this patient more than four years. He was well until November 1982, when he noticed weakness of left arm. In March 1983, he noticed hypogeusia and in July, he developed dysarthria and frozen gait. On admission, he was alert and oriented. Neurological examination revealed dysarthria, dysphagia and muscular weakness and atrophy in bilateral upper extremities, dominantly in left side. He showed remarkable frozen gait, retropulsion and could not walk. Brain CT showed mild dilatation of the third ventricle. In August 1988, he showed tongue atrophy, and weakness and atrophy of the extremities progressed during these four years. He also showed axial rigidity and frozen gait. Brain CT showed severe third ventricular dilatation and atrophy of tegmentum of the midbrain and cerebellum that were compatible with progressive supranuclear palsy (PSP). Six months later, he developed upper gaze palsy. From these findings, we concluded that this patient had a quite unique clinical features of both ALS and PSP.
Rinsho Shinkeigaku 1989 Sep
PMID:[A case of amyotrophic lateral sclerosis associated with clinical features of progressive supranuclear palsy]. 259 46

Serum acetylcholinesterase (AChE) and pseudocholinesterase (ChE) activity in infantile and juvenile spinal muscular atrophy (SMA) was determined. The total AChE activity was either normal or decreased in the childhood SMA (Type 1), the other SMA groups and disease controls (ALS, X-linked SMA). In the majority of SMA Type 1 cases (6/7 tested) an absence of the asymmetric A12 form was found. This was accompanied by changes in the other asymmetric and globular forms. The latter was, however, not specific for SMA Type 1 cases. The ChE activity was increased in the majority of SMA cases as well as disease controls. The asymmetric A12 ChE form was increased in all SMA Type 3 cases, the values of this form in SMA Type 1 was variable. A change in the ChE globular forms in SMA Type 1 and SMA Type 2 was a frequent finding. It is suggested that the absence of the asymmetric A12 AChE form in SMA Type 1 arises because of muscle cell immaturity and undeveloped muscle-nerve interactions. The reason of ChE changes is obscure.
Acta Neurol Scand 1989 Sep
PMID:Serum cholinesterase activity in infantile and juvenile spinal muscular atrophy. 280 Oct 18

Bone mass, as assessed by measurements of total subperiosteal diameter and medullary width of the second metacarpal bone on hand-wrist radiographs, was evaluated for 31 Guamanian patients (15 males, 16 females) with amyotrophic lateral sclerosis (ALS), 67 patients (39 males, 28 females) with parkinsonism-dementia (PD), and 66 (34 males, 32 females) nonaffected Guamanian controls. Comparisons between the two disease groups and between each disease group and the nonaffected controls were made taking into account the sex, age, and disability status of each participant. At all ages, ALS patients of both sexes had significantly lower percent cortical areas (PCA) than did nonaffected controls. The ALS males also had significantly lower PCA than PD males, although no significant differences were observed between female ALS and PD patients. The PD patients of either sex had a lower PCA when compared to controls, but the differences were not statistically significant. The observed differences in PCA were due solely to increased medullary width, suggesting that the diminished cortical bone thickness resulted from greater bone resorption rather than differential bone growth. Longitudinal studies support the cross-sectional findings of accelerated bone loss among ALS patients. It is not possible to determine from the present data whether the observed differences in PCA of the second metacarpal of the ALS patients are due to atrophy of the first interosseous muscle, to a generalized resorption process inherently associated with the development and progression of ALS, or to factors not accounted for by the present analysis.
Am J Phys Anthropol 1989 Sep
PMID:Bone mass in Guamanian patients with amyotrophic lateral sclerosis and parkinsonism-dementia. 280


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