Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030552 (paresis)
 5,831 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

This study used chemiluminescence, an "on-line" photon-counting technique, to detect and characterize activated O2 species in vitro and in isolated rat lungs. The sensitivity and specificity of enhanced chemiluminescence for superoxide anion (O2-.) and hydrogen peroxide (H2O2) was evaluated in vitro. The effect of media conditions (such as O2 tension, albumin concentration, and sulfhydryl group availability) on luminescence was assessed in vitro. Xanthine-xanthine oxidase (X-XO) primarily produced superoxide anion in vitro. Enhanced chemiluminescence varied directly with the dose of luminescent probe used and the quantity of activated O2 species administered. The strength of the luminescent signal was also dependent on the concentration of albumin and O2 in the media. Lucigenin was more sensitive than luminol to the presence of O2-. and, unlike luminol, lucigenin did not alter radical production by XO. However, neither luminescent probe was specific for O2-., as both detected H2O2 and O2 in vitro. H2O2-induced chemiluminescence was inhibited by catalase but not superoxide dismutase (SOD), while X-XO-induced luminescence was inhibited by SOD but not catalase. SOD-inhibitable chemiluminescence was a sensitive and specific marker for O2-. production in vitro. Once the sensitivity-specificity of enhanced chemiluminescence was defined in vitro, this technique was used to explore the mechanism by which exogenous X-XO reduced hypoxic vasoconstriction in isolated rat lungs. The vascular paresis, caused by administration of X-XO to the rat lung, resulted from a brief burst of O2-. production rather than a sustained alteration of lung radical levels.
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PMID:Detection of activated O2 species in vitro and in rat lungs by chemiluminescence. 253 94

We describe 36 patients (six were apparently sporadic cases and 30 were cases from nine families) with amyotrophic lateral sclerosis (ALS) characterized by a distinct phenotype associated with homozygosity for an Asp90Ala mutation in the CuZn-superoxide dismutase gene. The presenting motor manifestation in all patients was paresis in the legs, with slow progression to the upper extremities and finally to the bulbar muscles. The age of ALS onset varied from 20 to 94 years, with a mean of 44 years. Mean survival time was 13 years for the 11 deceased patients. However, this is probably biased and untypical (low) when compared with the disease duration in the surviving patients, and when considering other medical complications in the deceased patients. The rate of progression was highly variable, even within families. All patients showed signs of involvement of both upper and lower motor neurons. Other neurological features included painful muscle spasms and paraesthesiae in the lower extremities. Two-thirds of patients experienced difficulty with micturition. Electrophysiological studies confirmed the slow progression and spatial distribution of clinical symptoms in the peripheral motor system. Furthermore, [corrected] potentials evoked by transcranial magnetic stimulation (MEP) were compared with those evoked by cervical or lumbosacral electrical stimulation and often revealed marked slowing of transmission in central motor pathways. In Sweden and Finland ALS patients homozygous for the Asp90Ala mutation constitute a phenotypically characteristic subset of motor neuron disease.
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PMID:Autosomal recessive adult-onset amyotrophic lateral sclerosis associated with homozygosity for Asp90Ala CuZn-superoxide dismutase mutation. A clinical and genealogical study of 36 patients. 881 80

We propose a classification system for spinal muscular atrophies (SMA) based on the distribution of clinical signs, paresis and atrophy, as well as on the location of the responsible gene and the resulting enzyme deficiency, whenever these are known. This highly practical classification system encompasses three large SMA groups, as follows. A) Generalized forms, many of which are hereditary, are generally transmitted in a recessive autosomal manner. The course of disease is more severe when symptoms manifest early. Patients whose symptoms first occur after the first year of life often reach adolescence and even adulthood, confirming a highly apparent congruence of intermediate and pseudomyopathic juvenile forms. The same genetic defect, deletion in the 5q11-13.3 locus, that is responsible for acute infantile SMA has been demonstrated in both the aforementioned forms. B) Focal forms are restricted and often isolated cases; when they are hereditary, the genetic profile is highly heterogeneous. Though the disease will not necessarily evolve, it may progress to a generalized form. Focal forms may be symetric, assymetric, spinal-bulbar or multisegmental. The genetic abnormality has been identified for only some forms, such as chronic bulbar-spinal amyotrophy linked to the X-chromosome, at whose location, Xq11, the androgenic receptor is found. C) Amyotrophic lateral sclerosis (ALS) manifests clinically in a variety of ways and may be isolated, familial, juvenile or associated. Familial ALS is related to a gene defect in the 21q22.1 location that codifies for the superoxide dismutase enzyme. One juvenile form of ALS is related to a defect in the 2q33-35 chromosome. Any type of SMA can be related to degenerative neuronal disease of the central nervous system, especially juvenile ALS with generalized SMA, although such a link is at present merely an attractive hypothesis. Specific bibliographic references are given for each SMA form. Figures are provided to illustrate most of the SMA forms included in this classification system, the patients being at this time older adolescents and adults whose disease has been in evidence over many years.
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PMID:[Juvenile and adult forms of spinal muscular atrophies]. 904 73

1. Amyotrophic lateral sclerosis (ALS) is a degenerative disorder characterized by selective damage to the neural system that mediates voluntary movement. Although the pathophysiologic process of ALS remains unknown, about 5 to 10% of cases are familial. According to genetic linkage studies, the familial ALS (FALS) gene has been mapped on chromosome 21 in some families and recent work identified some different missense mutations in the Cu/Zn superoxide dismutase gene in FALS families. 2. We recently identified five mutations in six FALS families. The mutations identified in our FALS families are H46R, L84V, I104F, S134N, and V148I. The H46R mutation that locates in the active site of Cu/Zn SOD gene is associated with two Japanese families with very slow progression of ALS. On the other hand, the L84V mutation associated with a rapidly progressive loss of motor function with predominant lower motor neuron manifestations. 3. In the family with the V148I, the phenotype of the patient varied very much among the affected members. One case had weakness of the lower extremities at first and died without bulbar paresis. The second case first noticed wasting of the upper limbs with bulbar symptoms, but the third had weakness of upper extremities without developing dysarthria nor dysphagia until death. These mutations account for 50% of all FALS families screened, although Cu/Zn SOD gene mutations are responsible for less than about 13-21% in the Western population. 4. Our results indicate that the progression of disease with mutations of Cu/Zn SOD is well correlated with each mutation. The exact mechanism by which the abnormal Cu/Zn SOD molecules selectively affect the function of motor neurons is still unknown.
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PMID:Molecular analyses of the Cu/Zn superoxide dismutase gene in patients with familial amyotrophic lateral sclerosis (ALS) in Japan. 987 71

16 blood samples from Russian patients (Moscow) with idiopathic motor neuron disease were analysed for mutations in the CuZn-superoxide dismutase gene. Two patients (12.5%) with amyotrophic lateral sclerosis (ALS) were found to have a disease related mutation. One patient appears to have autosomal recessive adult-onset ALS associated with homozygosity for Asp90Ala and presents the characteristic phenotype of very slowly ascending paresis with both lower and upper motor neuron signs. The other patient heterozygous for Asp90Ala presents ALS with lumbar onset and rapid progression. Both of cases are apparently sporadic.
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PMID:[Sporadic amyotrophic lateral sclerosis associated with Asp90Ala CuZn-superoxide dismutase mutations in Russia]. 1066 86

Twenty blood samples from Russian patients (Moscow) with idiopathic motor neurone disease were analysed for mutations in the Cu,Zn superoxide dismutase (Cu,Zn SOD) gene. Two patients (10%) with the amyotrophic lateral sclerosis (ALS) form of the disease were found to have a disease-related mutation. One patient appears to have autosomal recessive adult-onset ALS associated with homozygosity for D90A and presents the characteristic phenotype of very slowly ascending paresis with both lower and upper motor neurone signs. Another patient, heterozygous for D90A, presents ALS with lumbar onset and rapid progression. This is the first report of a Cu,Zn SOD mutation in ALS in Russia.
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PMID:Sporadic ALS associated with the D90A Cu,Zn superoxide dismutase mutation in Russia. 1128 95

The Aspartate-90-Alanine (D90A) mutation on SOD-1 gene, the only known change causing recessive familial amyotrophic lateral sclerosis (FALS), is associated with a uniform phenotype characterized by slowly ascending paresis and long survival. Originally reported in Scandinavian cases, it has also been detected in patients from other countries. A common haplotype, probably of Scandinavian origin, has been demonstrated in D90A recessive pedigrees. In this study we screened the SOD-1 gene for the D90A mutation in 56 Italian patients from north-west Tuscany with sporadic ALS in order to evaluate the occurrence of this mutation and its genotype-phenotype correlation in Italy. We found the homozygous D90A mutation in one patient (1.8%), harboring the classical phenotype related to this mutation. No other mutations were detected in any of the five SOD-1 exons in our group. Our results confirm that recessive D90A mutation is present in Italy and it is associated with the phenotype already described A screening for that mutation, easily made by RFLP, should be made in sporadic ALS patients, especially where clinical investigation indicates its presence.
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PMID:A screening for superoxide dismutase-1 D90A mutation in Italian patients with sporadic amyotrophic lateral sclerosis. 1271 May 11

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease of motor neurons (MNs) that causes skeletal muscle paralysis. Familial forms of ALS are linked to mutations in the superoxide dismutase-1 (SOD1) gene. The mechanisms of human SOD1 (hSOD1) toxicity to MNs are unknown. We hypothesized that skeletal muscle is a primary site of pathogenesis in ALS that triggers MN degeneration. We created transgenic (tg) mice expressing wild-type-, G37R- and G93A-hSOD1 gene variants only in skeletal muscle. These tg mice developed age-related neurologic and pathologic phenotypes consistent with ALS. Affected mice showed limb weakness and paresis with motor deficits. Skeletal muscles developed severe pathology involving oxidative damage, protein nitration, myofiber cell death and marked neuromuscular junction (NMJ) abnormalities. Spinal MNs developed distal axonopathy and formed ubiquitinated inclusions and degenerated through an apoptotic-like pathway involving capsase-3. Mice expressing wild-type and mutant forms of hSOD1 developed MN pathology. These results demonstrate that human SOD1 in skeletal muscle has a causal role in ALS and identify a new non-autonomous mechanism for MN degeneration explaining their selective vulnerability. The discovery of instigating molecular toxicities or disease progression determinants within skeletal muscle could be very valuable for the development of new effective therapies for the treatment and cure of ALS.
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PMID:Skeletal muscle-restricted expression of human SOD1 causes motor neuron degeneration in transgenic mice. 2022 53

Familial cases of amyotrophic lateral sclerosis are most frequently caused by mutation in the superoxide dismutase-1 (SOD1) gene. We report a heterozygous I113F mutation in a patient with familial ALS characterized by early and predominant bilateral vocal cord paralysis followed by descending spinal cord paresis. Modelling of the mutant SOD1 showed an alteration of the protein secondary structure leading to impaired strength of the dimer interface. This may result in a failure of the protein folding and subsequently generation of toxic intracellular aggregates, suggesting a pathogenic role for the mutation.
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PMID:Vocal cord paralysis and rapid progressive motor neuron disease by the I113F mutation in SOD1 gene. 2141 51

Amyotrophic lateral sclerosis (ALS) is an aggressive rapidly progressing degeneration of both upper and lower motor neurons. Clinically, ALS is characterized by rapidly progressing atrophy and paresis of the muscles of the extremities. The genetics of ALS have become more complex in the last 5 years. The SOD gene is still very important; however, in recent years mutations in the genes for TDP-43 and FUS were discovered and also a most interesting intronic repeat expansion of the hexanucleotide repeat in C9ORF72 has been shown to be the most common in ALS. There are other quantitatively less relevant genes, which, however, are meaningful for pathogenetic aspects. It is also necessary to know that the phenotypes associated with ALS genetics have expanded.
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PMID:[Genetics of amyotrophic lateral sclerosis]. 2407 96


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