Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

---

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.
...
PMID:RNA-instructed DNA polymerase activity in a cytoplasmic particulate fraction in brains from Guamanian patients. 4 90

These studies were designed to determine if RIDP was present in a particulate fraction of brains from patients with ALS and PD. Evidence that we have detected RIDP is as follows: (a) DNA polymerase activity persists in the presence of concentrations of actinomycin D and distamycin that inhibit most DNA-directed DNA synthesis (25); (b) the majority of endogenous DNA polymerase activity is sensitive to prior treatment with RNase; (c) the early reaction product is a 4-5 S DNA heteropolymer joined by hydrogen bonds to an RNA molecule; and (d) the purified [3H]DNA product anneals to RNA extracted from the enzyme-containing pellet more extensively than to normal brain RNA or poly(rA). The enzyme activity is in a cytoplasmic particle that can be sedimented at high speed and has the buoyant density of RNA tumor viruses (1.16-1.18 gm/ml). This particulate fraction is not disrupted by physical manipulation and maintains its characteristic density with repeated centrifugations. Treatment with the nonionic surfactant Sterox changes the buoyant density of the enzyme-containing particle to 1.24 gm/ml, the density of the onconavirus virion core. Synthesis of RNA-DNA hybrids by an endogenous reverse transcriptase reaction was found only in normal and diseased Chamorro brains. Examination of a limited number of normal and diseased brains from individuals who lived in the United States produced negative results (39). Definitive characterization of this polymerase activity and identification as a true viral polymerase will depend on purification of biochemically active quantities of this polymerase to determine its template specificities, its cation preference, the fidelity of its transcription product, as well as its antigenic relationship to animal virus and human leukemic RIDP. Of critical importance in these studies will be differentiation of this activity from normal brain DNA polymerase gamma and terminal deoxynucleotidyltransferase.
...
PMID:RNA tumor viruses as causative agents of chronic neurological disease. 6 87

We studied exonic trinucleotide repeats and expression of androgen receptor (AR) gene in the spinal cord from an autopsied patient with X-linked spinal and bulbar muscular atrophy (SBMA). Forty-nine CAG triplet repeats were found in tissues from the spinal cord, cerebrum, cerebellum, cardiac muscle and bladder, while there were 20-24 CAG repeats in these tissues from control subjects, consisting of three patients with amyotrophic lateral sclerosis (ALS) and three patients with lung cancer. Thus, mitotic instability of the AR gene in SBMA may not occur at the level of somatic cells. To determine whether expression of the AR gene in the spinal cord of SBMA differs from that in control subjects, we used quantitative reverse transcriptase (RT)-PCR and Western blot. AR mRNA and protein were detected in the spinal cord from the patient with SBMA, but the levels of both AR mRNA and protein were less than those from the patients with ALS in whom the loss of motor neurons was similar to findings in the patient with SBMA. These findings suggest that structural alteration plus a reduced level of AR in the spinal cord are involved in the pathogenesis of SBMA, resulting in degeneration of motor neurons.
...
PMID:Exonic trinucleotide repeats and expression of androgen receptor gene in spinal cord from X-linked spinal and bulbar muscular atrophy. 751 6

We have identified a new mutant Cu/Zn superoxide dismutase (SOD1) deduced from the nucleotide sequences of peripheral blood lymphocyte mRNA from Japanese patients with familial amyotrophic lateral sclerosis (FALS). Sequence analysis of reverse transcriptase-initiated PCR amplified mRNA revealed a heterozygosity indicative of one normal allele and one variant allele with a T-->A transversion. This base change led to replacement of valine by glutamic acid at position 7 of 153-residue SOD1 molecule, and produced a new restriction site for Alu I in the exon 1. Restriction fragment length polymorphism analysis confirmed the linkage of this mutation with this type of FALS. Both enzymatic activity and protein of the SOD1 were reduced in red blood cells from the patient.
...
PMID:A new variant Cu/Zn superoxide dismutase (Val7-->Glu) deduced from lymphocyte mRNA sequences from Japanese patients with familial amyotrophic lateral sclerosis. 798 May 16

In earlier studies of sporadic amyotrophic lateral sclerosis (ALS), a disease of unknown etiology, the amount of metallothioneins (MTs), a group of small (6-7 kDa) metal-binding proteins, appeared higher in liver, kidney and spinal cord from patients than from non-neurologic controls. Immunohistochemically, the expression of MT in the central nervous system appeared limited to glia. Since the highly conserved MTs isotypes share antigenic epitopes, they could not be distinguished by immunological methods. It thus proved necessary to estimate the expression of each individual MT messenger ribonucleic acid (mRNA) by performing reverse transcriptase polymerase chain reaction (RT-PCR)-mediated analysis of tissue samples. Tissues selected included liver, motor cortex and cervical cord at C6; MT mRNAs analyzed included MT1A, 1B, 1E, 1F, 1G, 2A, and 3. Also, special care was taken to avoid interference by amplification of the 6 MT pseudogenes. Except of MT3, already known as brain-specific, and MT1B which was not expressed in any tissue, mRNA levels of the other MT genes tended to be higher in ALS than in control liver samples, but the differences did not attain statistical significance. In the nervous system, the diverse MT genes were expressed over a greater range in ALS than in controls, but exhibited no change in a consistent direction. At the motor cortex, changes seemed to be less pronounced than at C6. MT3 was expressed in the motor cortex and the cord. The results provide no evidence for either the induction of a specific MT repertoire, or for the inability of glia to express any MT gene in ALS. Because the semi-quantitative RT-PCR technique does not permit detailed comparisons between the subtypes of MT expressed in the various tissues, the question whether a single inductor may be held responsible for the elevation of MT in the ALS liver and nervous system remains open. In conclusion, ALS tissue remains capable of expressing all the major MT genes. MT, present in protoplasmic glia, arises locally and is not secondary to increases of hepatic or renal MT. Because MT3 is also expressed by the normal and ALS spinal cord, it is a central nervous system-specific and not only a brain-specific protein. Thus, the excess of MT in ALS liver seems to be an effect of slower catabolism rather than faster synthesis of protein.
...
PMID:Expression of different metallothionein messenger ribonucleic acids in motor cortex, spinal cord and liver from patients with amyotrophic lateral sclerosis. 890 18

Calpain is thought to be involved in muscular degradation in progressive muscular dystrophy (PMD), especially Duchenne and Becker muscular dystrophies. To assess the expression of calpain genes in skeletal muscles of patients with myopathies, we examined mRNA levels of three calpain isoforms by the quantitative reverse transcriptase-polymerase chain reaction method in biopsied muscles from control, PMD and amyotrophic lateral sclerosis (ALS) patients. There was a statistically significant increase in calpain 1 and calpain 2 mRNA levels in PMD and ALS patients as compared to controls. In contrast, there was a decrease in expression of calpain 3 mRNA in PMD, but it was not statistically significant. Expression of calpain 1 and calpain 2 positively correlated with each other, but not with calpain 3. These results indicate that expression of calpain 1 and calpain 2, but not calpain 3, are upregulated in diseased human muscles, likely playing a regulatory role in the process of myofibrillar degradation at the transcriptional as well as posttranslational level.
...
PMID:Expression of three calpain isoform genes in human skeletal muscles. 956 61

Recent evidence suggests that the growth associated protein GAP-43 is involved in the pathology of amyotrophic lateral sclerosis (ALS). In order to assess the primary structure of the GAP-43 mRNA expressed in the spinal cord of ALS patients, the total coding region of the GAP-43 mRNA was amplified from postmortem human spinal cord specimens using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. GAP-43 amplification products were clearly detected in all of the ALS cases but not in the normal controls. The GAP-43 mRNA and the deduced amino acid sequences from all ALS cases coincided completely with the sequence of human fetal GAP-43. These results suggest that the abnormal expression of GAP-43 mRNA underlying the pathogenesis of ALS is due to a quantitative increase, and that there are no qualitative abnormalities associated with a change in the amino acid sequences.
...
PMID:Primary structure of GAP-43 mRNA expressed in the spinal cord of ALS patients. 963 37

We investigated gene expression patterns of ion channels including the apamin-sensitive small-conductance Ca(2+)-activated K(+) (SK3) channel, the adult isoform of the skeletal muscle Na(+) channel (SkM1), the fetal isoform of skeletal muscle Na(+) channel (H1), and the Cl(-) channel (ClC-1) by using the semiquantitative reverse transcriptase-polymerase chain reaction (RT-PCR) for muscle samples from patients with adult onset myotonic dystrophy (DM), amyotrophic lateral sclerosis, and polymyositis. Patients with DM showed a significant increase in SK3 mRNA but not in mRNAs for other ion channels. The increased expression of SK3 gene in DM did not correlate with H1, the marker of muscle denervation, or the percentage of type 2C fiber, the marker of muscle regeneration.
...
PMID:The expression of ion channel mRNAs in skeletal muscles from patients with myotonic muscular dystrophy. 1109 Sep 82

Glutamate-mediated excitotoxicity is implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). The astroglial glutamate transporter EAAT2 plays a major role in maintaining low levels of extracellular glutamate in the central nervous system. Multiple EAAT2 mRNA transcripts have been described, but those retaining intron 7 or skipping exon 9 are reported to be specific to the motor cortex, spinal cord, and cerebrospinal fluid of ALS patients. We sought to verify these findings using a TaqMan (Elmer Biosystems, Warrington, UK) real-time reverse transcriptase polymerase chain reaction assay, which provides a sensitive and reliable quantitative measure of EAAT2 transcript copy ratios. We analyzed RNA extracted from frozen postmortem tissue from affected and unaffected central nervous system regions dissected from 17 sporadic ALS patients, 7 Alzheimer's disease patients, and 19 control subjects. We have demonstrated unequivocally that intron 7 retaining and exon 9 skipping variants can be detected in all individuals and in all central nervous system regions studied. The mean ratio of "variant" to "normal" transcripts did not differ significantly between patient and control groups. Although our assay could detect transcript concentrations in cerebrospinal fluid as low as 10 pg/ml, none were detected in 17 ALS and 8 control samples. We conclude that ALS is not associated with elevated levels of EAAT2 transcripts retaining intron 7 and skipping exon 9. An alternative explanation must be sought for the disturbance of glutamate homeostasis reported in ALS.
...
PMID:Intron 7 retention and exon 9 skipping EAAT2 mRNA variants are not associated with amyotrophic lateral sclerosis. 1135 55

The effects of prostaglandin (PG) E(1) on NO neurotoxicity were examined using rat cultured spinal neurons. Rat cultured spinal neurons exposed to the NO donor, 2,2'-(hydroxynitrosohydrazono) bis-ethanamine (NOC18), showed neurotoxic effects that were accompanied by apoptotic nuclear change, free radical generation, a reduction in glutathione, and mitochondrial dysfunction. PGE(1), at concentrations of 1-100 nM, protected cultured spinal neurons from NO toxicity by reversing the oxidative and pro-apoptotic properties elicited by NOC18 exposure. The administration of PGE(1) increased the intracellular cyclic AMP (cAMP) levels in cultured spinal neurons. In addition, reverse transcriptase-polymerase chain reaction (RT-PCR) analysis confirmed the existence of EP4, a cAMP-elevating PGE receptor, in cultured spinal neurons. The protective effects of PGE(1) against NO neurotoxicity was partially blocked by an inhibitor of MEK [the mitogen-activated protein kinase (MAPK)/extracellular-signal-regulated kinase (ERK) kinase], suggesting that the MAPK/ERK pathway may play a significant role in the activity of PGE(1). PGE(1) up-regulated the expression of the anti-apoptotic protein, Bcl-2, as determined by Western blot analysis. PGE(1) also induced the expression of thioredoxin in cultured spinal neurons. Our data indicate that PGE(1) exerts a protective action against NO neurotoxicity in cultured spinal neurons, and suggests a therapeutic potential of PGE(1) against spinal cord disease, such as amyotrophic lateral sclerosis.
...
PMID:Prostaglandin E1 protects cultured spinal neurons against the effects of nitric oxide toxicity. 1198 30


1 2 3 4 Next >>

---