Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042963 (vomiting)
 31,883 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypersensitivity to acetylcholinesterase inhibitors (anti-AChEs) causes severe nervous system symptoms under low dose exposure. In search of direct genetic origin(s) for this sensitivity, we studied six regions in the extended 22 kb promoter of the ACHE gene in individuals who presented adverse responses to anti-AChEs and in randomly chosen controls. Two contiguous mutations, a T-->A substitution, disrupting a putative glucocorticoid response element, and a 4-bp deletion, abolishing one of two adjacent HNF3 binding sites, were identified 17 kb upstream of the transcription start site. Allele frequencies for these mutations were 0.006 and 0.012, respectively, in 333 individuals of various ethnic origins, with a strong linkage between the deletion and the biochemically neutral H322N mutation in the coding region of ACHE. Heterozygous carriers of the deletion included a proband who presented with acute hypersensitivity to the anti-AChE pyridostigmine and another with unexplained excessive vomiting during a fourth pregnancy following three spontaneous abortions. Electromobility shift assays, transfection studies and measurements of AChE levels in immortalized lymphocytes as well as in peripheral blood from both carriers and non-carriers, revealed functional relevance for this mutation both in vitro and in vivo and showed it to increase AChE expression, probably by alleviating competition between the two hepatocyte nuclear factor 3 binding sites. Moreover, AChE-overexpressing transgenic mice, unlike normal FVB/N mice, displayed anti-AChE hypersensitivity and failed to transcriptionally induce AChE production following exposure to anti-AChEs. Our findings point to promoter polymorphism(s) in the ACHE gene as the dominant susceptibility factor(s) for adverse responses to exposure or to treatment with anti-AChEs.
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PMID:A transcription-activating polymorphism in the ACHE promoter associated with acute sensitivity to anti-acetylcholinesterases. 1081 9

This study explores the relationship of the pain of the migraine headache and the associated features of migraine. Migraineurs (n=1025) (ICHD-2, 1.1-1.2 and 1.5.1) were evaluated retrospectively using a detailed database (daily unremitting excluded). Variables studied included headache intensity and duration, associated symptoms and pain characteristics. Non-parametric correlations were used to evaluate relationships among variables. Headache intensity correlated with nausea, vomiting, photophobia, phonophobia, dizziness (all P=0.000), running of the nose/tearing of the eyes (P=0.007), and osmophobia (P=0.044), but not with diarrhoea or taste abnormality. Headache duration correlated only with osmophobia (P=0.002) and taste abnormality (P=0.005). Throbbing, pressure and stabbing pain correlated with most of the associated symptoms. Aching correlated only with taste abnormality. This correlational study demonstrates that migraine pain is clearly related to nausea, but is also correlated with other associated migraine symptoms. Taste abnormality and osmophobia are better correlated with headache duration rather than headache intensity.
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PMID:The relationship between migraine pain and other associated symptoms. 1667 63