Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004134 (ataxia)
 15,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence from microinjection studies in anesthetized rats suggests that central excitatory amino acid pathways using N-methyl-D-aspartate receptors are involved in the regulation of the cardiovascular system. To test the hypothesis that these pathways are tonically involved in the maintenance of or the baroreceptor reflex regulation of cardiovascular function, we have examined the effects of intravenous injection of the centrally acting, noncompetitive N-methyl-D-aspartate receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d]cyclohepten-5,10-imine (MK-801), on the mean arterial pressure, heart rate, renal sympathetic nerve activity, and behavior of conscious, freely moving sham-operated and sinoaortic baroreceptor-denervated rats. Administration of MK-801 produced, within 5 minutes, dose-dependent elevations in mean arterial pressure, heart rate, and renal sympathetic nerve activity that were sustained for 0.5 to 2.5 hours. For an equivalent dose, MK-801 produced approximately twice the peak changes in mean arterial pressure and heart rate in the sinoaortic baroreceptor-denervated rats than in the sham-operated rats. Pretreatment results were as follows: 1) The ganglion blocker chlorisondamine markedly attenuated the hypertension and tachycardia in the sham-operated and sinoaortic baroreceptor-denervated rats, 2) pretreatment with the alpha 1-adrenergic receptor antagonist prazosin virtually abolished the hypertension, and 3) the beta 1-adrenergic receptor antagonist atenolol markedly reduced the tachycardia. MK-801 also produced stereotypic behaviors and ataxia in the sham-operated and sinoaortic baroreceptor-denervated rats; however, qualitatively and quantitatively similar changes in behavior were induced in the latter by doses approximately five time lower than required in sham operated rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cardiovascular effects of the N-methyl-D-aspartate receptor antagonist MK-801 in conscious rats. 254 22

The Shaker family voltage-dependent potassium channels (Kv1) are expressed in a wide variety of cells and are essential for cellular excitability. In humans, loss-of-function mutations of Kv1 channels lead to hyperexcitability and are directly linked to episodic ataxia and atrial fibrillation. All Kv1 channels assemble with beta subunits (Kv betas), and certain Kv betas, for example Kv beta 1, have an N-terminal segment that closes the channel by the N-type inactivation mechanism. In principle, dissociation of Kv beta 1, although never reported, should eliminate inactivation and thus potentiate Kv1 current. We found that cortisone increases rat Kv1 channel activity by binding to Kv beta 1. A crystal structure of the Kv beta-cortisone complex was solved to 1.82-A resolution and revealed novel cortisone binding sites. Further studies demonstrated that cortisone promotes dissociation of Kv beta. The new mode of channel modulation may be explored by native or synthetic ligands to fine-tune cellular excitability.
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PMID:Cortisone dissociates the Shaker family K+ channels from their beta subunits. 1893 45

Mutations in the gap junction protein beta 1 gene (GJB1) cause X-linked Charcot-Marie-Tooth disease type 1 (CMTX1). CMTX1 is representative of the intermediate type of CMT, having both demyelinating and axonal neuropathic features. We analyzed the clinical and genetic characterization of 128 patients with CMTX1 from 63 unrelated families. Genetic analysis revealed a total of 43 mutations including 6 novel mutations. Ten mutations were found from two or more unrelated families. p.V95M was most frequently observed. The frequency of CMTX1 was 9.6% of total Korean CMT family and was 14.8% when calculated within genetically identified cases. Among 67 male and 61 female patients, 22 females were asymptomatic. A high-arched foot, ataxia, and tremor were observed in 87%, 41%, and 35% of the patients, respectively. In the male patients, functional disability scale, CMT neuropathy score, and compound muscle action potential of the median/ulnar nerves were more severely affected than in the female patients. This study provides a comprehensive summary of the clinical features and spectrum of GJB1 gene mutations in Korean CMTX1 patients.
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PMID:Clinical characterization and genetic analysis of Korean patients with X-linked Charcot-Marie-Tooth disease type 1. 2844 91

X-linked Charcot-Marie-Tooth disease (CMT 1X) is the second most common form of inherited demyelinating neuropathy. It is established that patients suffering from CMT 1X can have episodes of hemiparesis, paraparesis, quadriparesis, ataxia, aphasia, and dysarthria, which can be fully reversible, and 'trigger' factors for these episodes are usually febrile illness, high altitudes, hyperventilation, and physical activity. We describe a 22-year-old patient with a history of viral infection and sleep deprivation who presented to our department because of acute difficulty in walking and neurophysiological findings suggesting Guillain-Barre syndrome. The patient's phenotype was compatible with CMT disease and within hours he showed remarkable improvement of his muscle strength without receiving any medical treatment. Any other metabolic, infectious, vasculitic, hematological, paraneoplastic, or infiltrative cause of polyneuropathy was excluded with laboratory work-up. Diagnosis of CMT 1X was confirmed with repeated neurophysiological study and genetic testing of his and his mother's blood, demonstrating the Arg75Trp [CGG to TGG,(R75W)] mutation on exon2 of gap junction protein beta 1. CMT 1X should be considered in patients with a phenotype compatible with the disease, rapid improvement of their clinical manifestations, and neurophysiological findings consistent with a hereditary, demyelinating neuropathy.
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PMID:Charcot-Marie-Tooth Disease 1X Simulating Paraparetic Guillain-Barre Syndrome. 2909 25