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)

We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [(18)F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment.
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PMID:Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates. 1603 Jan 81

It is well known that selenium plays a fundamental role in regulating thyroid and other functions of the human body like reproduction, autoimmunity, glucose metabolism or bone metabolism. While for thyroid function investigation, radioimmunoassays and radioimmunometric assays both key techniques of nuclear medicine are used, for selenium measurements atomic absorption spectrometry is the method of choice. Normal thyroid gland retains high selenium concentrations even under conditions of inadequate selenium supply and expresses many of the known selenocysteine-containing proteins. Adequate selenium nutrition supports efficient thyroid hormone synthesis and metabolism and protects the thyroid gland damage by excessive iodide exposure. In regions where a combined severe iodine and selenium deficiency exist, normalization of iodine supply is mandatory before initiation of selenium supplementation in order to prevent hypothyroidism. Selenium deficiency and disturbed thyroid function may develop under conditions of special dietary regimens, such as long-term total parenteral nutrition or after inadequate nutrition in children. Some investigators suggest that selenium may be a useful adjunctive treatment for autoimmune thyroid diseases, such as Hashimoto and Graves' disease. Low serum selenium levels have been associated with higher incidence of thyroid cancer, as well as with chronic illness or lomicronw triiodothyronine syndrome. These biological actions are mediated through the expression of selenoproteins, the most important being the glutathione peroxidases, the iodothyronine deiodinases, the thioredoxine reductase and the selenoprotein P. Selenium is also associated with animal proteins. Subsequently meats and seafood are dietary sources of selenium. The ingestion of large quantities of selenium may have adverse effects. It has been shown that dietary intake of about 300 micro g of selenium daily may have a toxic effect on growth hormone and insulin like growth factor-1 metabolism, as well as in the synthesis of thyroid hormones. Main adverse effects may be anorexia, diarrhea, depression, hemorrhage, liver and kidney necrosis, blindness, ataxia and respiratory disturbances. Dermatitis and CNS deficiency have also been described. It is concluded that selenium plays an important role in regulating thyroid function, as well as in the homeostasis of thyroid hormones through the action of selenoproteins, in which it incorporates as selenocystein.
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PMID:[Selenium and thyroidal function; the role of immunoassays]. 1745 Feb 51

Well-differentiated thyroid cancer accounts for 95% of thyroid malignancies. In contrast to medullary thyroid carcinoma, in which about 25% are familial, only 5% of follicular cell-derived thyroid carcinomas are a component of a familial cancer syndrome. The familial follicular cell-derived tumors or nonmedullary thyroid carcinoma encompass a heterogeneous group of diseases, and are classified into 2 distinct groups: syndromic-associated tumors, occurring in syndromes in which nonmedullary thyroid carcinomas are the predominant tumor encountered, and nonsyndromic tumors, those occurring in tumor syndromes in which thyroid involvement is a minor component. The first group, syndromic-associated tumors, includes phosphase and tensin (PTEN)-hamartoma tumor syndrome/Cowden syndrome, familial adenomatous polyposis/Gardner syndrome, Carney complex type 1, Werner syndrome, and Pendred syndrome. Other syndromes, as McCune Albright syndrome, Peutz-Jeghers syndrome, and Ataxia-teleangiectasia syndrome may be associated with the development of follicular cell-derived tumors, but the link is less established than the above syndromes. The syndromic-associated tumors are the focus of this review. The second group of familial follicular cell-derived tumors syndromes or nonsyndromic tumors, in which nonmedullary thyroid carcinomas are the major findings, include pure familial papillary thyroid carcinoma, with or without oxyphilia, familial papillary thyroid carcinoma with papillary renal cell carcinoma, and familial papillary thyroid carcinoma with multinodular goiter. This review will discuss the clinical and pathological findings of the patients with familial syndrome-associated tumors: PTEN-hamartoma tumor syndrome/Cowden syndrome, familial adenomatous polyposis syndrome, Carney complex type 1, Werner syndrome, and Pendred syndrome.
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PMID:Thyroid cancer of follicular cell origin in inherited tumor syndromes. 2096 48