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)

The binding of 3H-quinuclidinyl benzilate, a muscarinic cholinergic antagonist, of 3H-dihydroalprenolol, a beta adrenergic antagonist, and of 3H-flunitrazepam, a ligand which labels benzodiazepine receptors, was examined in several regions of control and Friedreich's ataxia (FA) brains. 3H-Quinuclidinyl benzilate binding appeared to increase in the inferior olivory nucleus, anterior and posterior cerebellar vermi but was unaltered in the dentate nucleus and cerebellar hemisphere of FA brain. The binding of 3H-dihydroalprenolol seemed to increase in the inferior olivary nucleus yet was not different from controls in the dentate nucleus, cerebellar hemisphere, anterior and posterior cerebellar vermi of FA brains. 3H-Flunitrazepam binding was slightly lowered in the inferior olivary and dentate nuclei but was unchanged in the other FA brain regions examined. The present study suggests possible trends in neurotransmitter receptor alterations in post-mortem brain tissue of FA patients.
 ...
PMID:Brain neurotransmitter receptors in Friedreich's ataxia. 22 58

Studies were undertaken to further characterize plasma lipids and lipoprotein abnormalities in Friedreich's ataxia. The high density lipoprotein (HDL) apo AI/AII ratio was quantitated by densitometry and found to be normal. The free to esterified cholesterol ratio in HDL was lower in Friedreich's ataxia because of a reduction in the amount of free cholesterol in this lipoprotein class. The fatty acid profile of the cholesteryl-ester (CE) fraction was markedly deficient in linoleic acid (18:2) in both total plasma and HDL. There was a compensatory increase in saturated acids. The HDL phospholipid (PL) fraction also showed a reduction in the proportion of 18:2 with a concomitant increase in stearic (18:0) and oleic acid (18:1) while the HDL triglyceride (TG) fraction showed only an increase in palmitoleic (16:1) and oleic acids. Feeding of soya lecithin rich in 18:2 failed to increase significantly the 18:2 content of HDL-CE and HDL-PL but lowered the percentage of 16:1 and 18:1 in all 3 lipid classes of HDL. Although the total plasma CE fatty acid profile was perturbed in Friedreich's Ataxia, total plasma PL and TG fatty acid patterns were unaffected. Among the plasma lipoprotein fatty acid profiles, that of the low density lipoprotein (LDL) was most affected, then that of the HDL. The very low density lipoprotein (VLDL) fatty acid composition showed an increase in 16:1 and a decrease in 18:2 which were entirely corrected by lecithin feeding. These results suggest the existence of a metabolic defect in the incorporation of 18:2 into chylomicron phospholipids within the intestinal mucosa.
 ...
PMID:Fatty acid profile of major lipid classes in plasma lipoproteins of patients with Friedreich's ataxia-demonstration of a low linoleic acid content most evident in the cholesterol-ester fraction. 22 59

Electron spin resonance, scanning electron microscopic, and SDS-polyacrylamide gel electrophoretic studies of erythrocytes in Friedreich's ataxia have been performed. No alteration in the physical state of membrane lipids, in morphology, or in the staining profile of erythrocytes in Friedreich's ataxia could be demonstrated. An altered conformation and/or organization of proteins in erythrocyte membranes in this disorder was suggested by spin labeling studies (P less than 0.025), favoring the possibility of a generalized membrane abnormality in Friedreich's ataxia. These findings are discussed in relation to other inherited neurological diseases where similar studies have been performed.
 ...
PMID:Evidence for an altered physical state of membrane proteins in erythrocytes in Friedreich's ataxia. 22 60

The value of evoked potentials in studying conduction in the somatosensory pathway was assessed in patients with various neurological disorders. In patients with multiple sclerosis (MS) abnormalities of the cervical response (N14) were found particularly in longstanding cases but also in the early stages of the disease, even in patients without sensory symptoms or signs, and were reversible in some patients. The cortical response was also abnormal in some cases but the two were not always affected together. In Friedreich's ataxia both the cervical and cortical responses were usually abnormal. Subclinical abnormalities of the cervical responses were found in some patients with hereditary spastic paraparesis or mixed forms of spinocerebellar ataxia. The cervical responses were also abnormal in patients with peripheral neuropathy and cervical radiculopathy, and in some patients with brain-stem or thalamic lesions. Cervical and cortical responses were normal in the lateral medullary syndrome, whereas the cortical response was markedly abnormal in patients with high brain-stem or cerebral hemisphere vascular lesions. Cortical and subcortical responses were abnormal in some patients with stereotactic thalamic lesions. Enhanced cortical responses were found in patients with lesions at different levels in the CNS. The most marked enhancement was observed in patients with familial myoclonic epilepsy. Lesser degrees were found in some patients with MS, progressive supranuclear palsy, thalamic lesions, brain-stem encephalitis and syringomyelia. Enhanced responses were usually found in patients with minimal or no clinical sensory involvement. It is postulated that this type of abnormality results from an interference to the inhibitory mechanisms which normally operate at various levels in the somatosensory pathway. It is concluded that evoked potential studies are a valuable adjunct to the clinical evaluation of sensation, and that they may provide useful information on the pathophysiology of conduction in the somatosensory pathway.
 ...
PMID:The contribution of evoked potentials in the functional assessment of the somatosensory pathway. 22 50

Abetalipoproteinaemia (Bassen-Kornzweig syndrome), an autosomal recessive inherited disease, up to now has been described in 53 instances in the world literature. Neurological symptoms were reported in 34 of them. Ataxia, loss of proprioceptive sensation, and areflexia characterize this disorder, resembling Friedreich's ataxia. Other signs, which may be inconstantly found, are weakness, diminution of cutaneous sensation, and in the later course an atypical retinitis pigmentosa. Laboratory examinations show acanthocytosis, lowered concentrations of serum cholesterol, triglycerides and phospholipids and as the pathognomonic feature of this disease absence of beta-lipoproteins. Reduced serum concentrations of fat soluble vitamin are secondary effects of this metabolic disorder. In a few cases there are connections to familial hypobeta-lipoproteinaemia, which is autosomal dominantly inherited. Therapeutic trials with a controlled dietary intake of fat may cause an improvement of clinical symptoms, additional doses of fat-soluble vitamin, if given during the early stages of the disease are said to prevent from retinopathy but do not seem to influence the development and course of neuropathy.
 ...
PMID:[Neurological symptoms in a-beta-lipoproteinemia (author's transl)]. 25 73

A family had three siblings affected with classic Friedreich's ataxia. One sibling died at age 20 with fulminant diabetic ketoacidosis. The other two affected siblings are identical twin sisters without clinical diabetes but with an abnormality in the metabolism of exogenously administered glucose. These twins also have abnormal hypothalamic-pituitary control of prolactin and possibly of growth-hormone secretion. This study extends the previous reports of endocrine deficienceis associated with Friedreich's ataxia. The mechanisms underlying this association are undetermined but could represent pleiotropic effects of the Friedreich's ataxia gene or secondary manifestations of the primary central nervous system degeneration, or both.
 ...
PMID:Abnormal function of endocrine pancreas and anterior pituitary in Friedreich's ataxia. Studies in a family. 34 4

The regulation of cytoplasmic calcium is a key process in nerve tissue. Using a smooth muscle model we have shown that prostaglandin (PG) E2 probably regulates entry from extracellular fluid, whereas the release from intracellular stores depends on the interplay between thromboxane (TX) A2, PGEI and prostacyclin. Hormones and other agents interact with this system in the following ways: vasopressin, angiotensin and inositol mobilize arachidonic acid from membrane phospholipids and increase synthesis of PGE2 and TXA2, cortisol blocks this action. Prolactin and zinc mobilize dihomo-gamma-linolenic acid and increase synthesis of PGEI. These effects can be blocked by cortisol, lithium and taurine, three agents which on their own have no effect on basal PG production. Epileptogenic agents like penicillin and picrotoxin also stimulate PG synthesis, while diphenylhydantoin is a PG antagonist and diazepam is a TXA2 antagonist. The effects of all these agents occur at concentrations which are physiological in the case of the natural ones, and readily attained in human plasma in the case of the drgus. In view of recent evidence that calcium may be important in demyelination and considering the established role it plays in nerve conduction and synaptic transmission, we suggest that these observations may be of significance in understanding Friedreich's ataxia.
 ...
PMID:Regulation of cytoplasmic calcium: interactions between prostaglandins, prostacyclin, thromboxane A2, zinc, copper and taurine. 34 85

A number of excellent and comprehensive reviews on various aspects of pyruvate dehydrogenase multienzyme complex have been written recently. The purpose of the present review is to summarize briefly the reaction mechanism and the regulation of this enzyme. Emphasis is put on the most recent literature not covered by previous reviews. Particular attention is also paid to the regulation of brain pyruvate dehydrogenase multienzyme complex, since a number of patients with neuromuscular diseases, such as Friedreich's ataxia, show a decreased rate of pyruvate oxidation.
 ...
PMID:Regulation of brain pyruvate dehydrogenase multienzyme complex. 35 1

A spinocerebellar degeneration is described affecting ten members of a family over five generations with transmission by X-linked recessive inheritance. The clinical features include pes cavus, scoliosis, increased lumbar lordosis and signs of cerebellar dysfunction. There is a slowly progressive distal muscle atrophy, pyramidal weakness, brisk tendon jerks and the plantar responses are extensor. Sensory abnormalities were observed only in the two eldest members and consisted of mild impairment of position and vibration sense. A sural nerve biopsy showed loss of large diameter fibres and uniformly short internodal lengths as is usually found in Friedreich's ataxia. However, the electrophyisological findings of retained sensory action potentials and reduced motor conduction velocities contrast with those of Friedreich's ataxia. Post-mortem examination of one of the affected members revealed spinal cord pathology similar to that seen in Friedreich's ataxia with degeneration of the dorsal columns, and spinocerebellar and corticospinal tracts although the loss of Purkinje cells in the cerebellum was greater than is usually seen in that condition.
 ...
PMID:A spinocerebellar degeneration with X-linked inheritance. 42 31

Charcot-Marie-Tooth disease (peroneal muscular atrophy) has been reported to cause cardiac arrthymias and conduction disturbances in association with peripheral muscle atrophy. To establish more accurately the frequency of such cardiac disorders in this disease, 68 patients with Charcot-Marie-Tooth disease were evaluated prospectively for evidence of cardiac involvement. Cardiac findings were limited to five patients with conduction defects, two patients with supraventricular tachycardia, two patients with ischemic heart disease, and 20 with mitral valve prolapse. The frequency of each of the abnormal cardiac findings, with the possibly emalities in the population at large. The low incidence of cardiac involvement in patients with Charcot-Marie-Tooth disease may be helpful in distinguishing this disorder from Friedreich's ataxia, an entity that may mimic Charcot-Marie-Tooth disease but that is frequently associated with heart disease.
 ...
PMID:Cardiac findings in Charcot-Marie-Tooth disease. A prospective study of 68 patients. 48 49


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>