Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0016719 (Friedreich's ataxia)
 2,098 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Platelets of a patient with Friedreich's ataxia have been investigated because of a codiagnosis of thrombasthenia. No aggregation occurred in response to adenosine diphosphate, platelet activating factor-acether, a stimulatory antiplatelet monoclonal antibody, or phorbol myristate acetate, although platelet aggregation could be induced with thrombin, the calcium ionophore A23187, or high concentrations of collagen. Shape change, adenosine triphosphate secretion, and the responses of the platelets' protein phosphorylation systems to all agonists were normal. Immunologic analysis of the patient's radiolabeled platelet surface proteins revealed normal levels of glycoproteins IIB and IIIa. However, no iodine 125-fibrinogen binding occurred after stimulation of the patient's platelets with adenosine diphosphate. In contrast, pretreatment of the patient's platelets with the proteolytic enzyme alpha-chymotrypsin resulted in the exposure of active 125I-fibrinogen binding sites. The patient's platelets exhibited normal aggregation to fibrinogen after their pretreatment with chymotrypsin and with elastases derived either from porcine pancreas or from human granulocytes. A murine monoclonal antibody directed against the human platelet membrane glycoproteins IIb and IIIa calcium-dependent epitope and rabbit polyclonal anti-human platelet membrane and human anti-P1A1 antibodies immunoprecipitated glycoproteins IIb and IIIa and a 66 kd cleavage product of glycoprotein IIIa from sodium dodecyl sulfate-Triton X-100 extracts of the patient's proteolytically treated platelets. The patient appears to exhibit a unique type of thrombopathy involving a defect in the exposure of fibrinogen receptors. The association between the neurologic disorder and the platelet defect is still unclear.
 ...
PMID:Identification of a unique type of thrombopathy of human platelets: defect in the exposure of active fibrinogen receptors in a patient with Friedreich's ataxia. 283 36

Thirty-three children presenting with "primitive" cardiomyopathy observed from January 1984 to December 1985 underwent a protocol of investigations consisting of histo-enzymatic study of the deltoid muscle, metabolic studies (glucose, free fatty acids, lactate, pyruvate, 3-hydroxybutyrate, aceto-acetate, carnitine, amino-acids blood levels after a 15 hour-fast; urinary organic acids chromatography) and a study of the fatty acids oxidation in cultured fibroblasts. In all children cardiac involvement was predominant and had been the cause for hospitalization. Cardiomyopathies of the hypertrophic type have an early onset, most often are part of a complex picture of extra-cardiac involvement and frequently have a lethal evolution. On the contrary, hypokinetic dilated cardiomyopathies are most often isolated, have a later onset and a less severe course. In 2 cases, an early hypokinetic dilated cardiomyopathy evolved toward hypertrophy. Peripheral muscular involvement is very frequent (lipidosis, mitochondrial aggregates or specific aspects) (60% of cases) in dilated as well as hypertrophic types. A precise etiological diagnosis or a strong presumption was possible in 12 of 33 cases: 2 with hereditary deficiency of the fatty acids beta-oxidation, 1 carnitine systemic deficiency, 1 Friedreich ataxia, 1 central core disease, 1 coxsackie B1 myocarditis, 6 strong suspicions of respiratory chain deficiency.
 ...
PMID:[Apparently idiopathic primary myocardiopathies in children. The role of metabolic etiology]. 344 58

Mitochondrial and cytosolic malic enzymes were assayed radiochemically in fibroblasts from six patients suffering from Friedreich's ataxia in order to verify earlier reports of abnormalities in these enzymes. No abnormalities could be detected in the activities of either enzyme. On cellulose acetate electrophoresis a band of enzyme activity corresponding to the mitochondrial isoenzyme was detectable contrary to earlier reports. Possible explanations for the disparity of results between different laboratories are discussed.
 ...
PMID:Mitochondrial malic enzyme in Friedreich's ataxia: failure to demonstrate reduced activity in cultured fibroblasts. 397 24

A series of aza analogues (4-9) of the experimental neuroprotective drug idebenone (1) have been prepared and evaluated for their ability to attenuate oxidative stress induced by glutathione depletion and to compensate for the decrease in oxidative phosphorylation efficiency in cultured Friedreich's ataxia (FRDA) fibroblasts and lymphocytes and also coenzyme Q10-deficient lymphocytes. Modification of the redox core of the previously reported 3 improved its antioxidant and cytoprotective properties. Compounds 4-9, having the same redox core, exhibited a range of antioxidant activities, reflecting side chain differences. Compounds having side chains extending 14-16 atoms from the pyrimidinol ring (6, 7, and 9) were potent antioxidants. They were superior to idebenone and more active than 3, 4, 5, and 8. Optimized analogue 7 and its acetate (7a) are of interest in defining potential therapeutic agents capable of blocking oxidative stress, maintaining mitochondrial membrane integrity, and augmenting ATP levels. Compounds with such properties may find utility in treating mitochondrial and neurodegenerative diseases such as FRDA and Alzheimer's disease.
...
PMID:An optimized pyrimidinol multifunctional radical quencher. 2490 Jul 38