Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0018799 (heart disease)
 34,133 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We have investigated an Italian family with generalized resistance to thyroid hormone (RTH), consisting of two individuals with elevated serum thyroid hormones (TH) and a non-suppressed TSH, together with unaffected family members, for a mutation in the thyroid hormone receptor beta gene (hTR beta). We have identified a single nucleotide substitution (1321 CTT to GTT) corresponding to a leucine to valine substitution at codon 346 (L346V) in the predicted protein. The index case and her affected child are heterozygous for the receptor defect, with normal sequence in unaffected family members. Furthermore, both parents of the index case were unaffected, suggesting that the mutation had arisen de novo. When expressed in vitro, the L346V mutant receptor showed a marked reduction in its affinity for tri-iodothyronine (T3), impaired ligand-dependent transactivation and potent dominant negative activity. Its functional impairment could not be alleviated, even at supraphysiological concentrations of T3, suggesting that the mutation might interfere with the intrinsic ligand-dependent transactivation function (AF-2) located in the hormone binding domain of hTR beta. Finally, the presence of the L346V mutation in the son of the propositus, who died from complications associated with congenital heart disease, raises the possibility that RTH might have contributed to the pathogenesis or severity of the latter.
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PMID:Identification and characterization of a novel de novo mutation (L346V) in the thyroid hormone receptor beta gene in a family with generalized thyroid hormone resistance. 936 5

Chronic daily headache (CDH) is one of the more frequently observed headache syndromes at major tertiary care centers. CDH is defined as headache occurring >15 days/month. Different mechanisms are involved in the development of CDH but what factors specifically contributing to the transformation from episodic into CDH remain largely unknown. Analgesic overuse is commonly identified as the most important factor for such transformation. Hypertension, allergy, asthma, arthritis, diabetes, obesity and hypothyroidism were associated with CDH in clinical series. The objective of this study is to identify risk factors of chronicity in patients with headache. A total of 1,483 consecutive patients were studied. We collected information on age, gender, headache type and comorbidity. Patients were divided into three diagnostic groups: migraine and tension-type headache (CTT) diagnosis were made according to ICHD-II, and CDH fulfilling the Proposal Headache Classification for Chronic Daily Headache described by Silberstein and Lipton (in Chronic daily headache including transformed migraine, chronic tension-type headache, and medication overuse, 2001). We used descriptive statistics and Chi-square test. Our data show that age, gender and headache onset were similar in the three groups. Diabetes, hypercolesterolaemia, smoke and cardiopathy prevalence did not differ in the three groups (P > 0.05). Hypertension prevalence in CDH group (16.2%) was significantly higher than in the other two groups (migraine 7.3%; CTT 6.6%; P < 0.01). There were no differences (P > 0.05) in hypertension prevalence between CDH with and without medication overuse. CDH patients (mean age 41.8 +/- 14) referred to the Headache Center later than migraine and CTT patients (mean age 37 +/- 12) (P > 0.05). According to previous studies we found that hypertension is more frequent in CDH than in migraine and CTT. Examining this result it is possible to conclude that there exists an association between CDH and hypertension, but not that a causal relationship necessarily exists. Considering the other somatic conditions we did not find any correlation. The potential role of somatic comorbidity in CDH has to be studied in further clinical trials.
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PMID:Hypertension is a factor associated with chronic daily headache. 2046 15