Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Apolipoprotein (apo) B-100 mRNA is edited in the small intestine (in all mammals examined) and the liver (in mice and rats only) to produce apoB-48 mRNA. ApoB mRNA editing involves a C-->U conversion of the first base of the codon CAA for Gln-2153 in apoB-100, changing it to an in-frame stop codon (UAA). The edited mRNA encodes apoB-48, which is colinear with the N-terminal 48% of apoB-100. ApoB mRNA editing can be reproduced in vitro using cellular extracts from one species to edit synthetic apoB mRNA sequences from a different species. Editing of transcripts from transfected genes also appears not to be species-specific. We have produced transgenic mice that express full-length human apoB-100 mRNA at high levels in the liver and small intestine. Human apoB-100 (a 550-kDa protein) but not apoB-48 (a 260-kDa protein) is detected in total plasma (at approximately 22 mg/dl) and in very low density and low density lipoproteins. The endogenous mouse plasma apoB concentration is reduced by approximately 45% in the transgenic animals. Thus, the transgenic mice form an animal model for familial hyperapolipoprotein B, an inherited form of hyperlipidemia. To our surprise, we found that the full-length human apoB mRNA consists of > 99% apoB-100 mRNA in both the liver and small intestine; < 1% of edited (apoB-48) mRNA was detected. The proportions of endogenous mouse apoB-48 (edited) mRNA (60 and 90% in the liver and small intestine, respectively) were identical in transgenic mice and their nontransgenic littermates. Therefore, full-length human apoB mRNA is resistant to editing by the mouse editing enzyme in vivo; the unchanged proportion of endogenous mouse apoB-48 mRNA in the transgenic mice suggests that the human mRNA competes poorly with the mouse sequence for interacting with the editing enzyme. This observation has implications for the sequence specificity and mechanism of RNA editing. Furthermore, we should exercise caution in the interpretation of in vitro RNA-editing experiments.
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PMID:Transgenic mice expressing full-length human apolipoprotein B-100. Full-length human apolipoprotein B mRNA is essentially not edited in mouse intestine or liver. 835 69

Although cumulative evidence indicates that risk factors for arteriosclerosis have an impact on age-related changes in brain pathology, the influence of aging without major risk factors on changes in brain structures has not yet been fully elucidated. We used magnetic resonance imaging (MRI) to study how aging affects structural changes in the brain (eg, white matter lesions, hippocampal atrophy [HA], microbleeds) in normal subjects without major risk factors for cerebrovascular diseases. We studied 1108 subjects who underwent voluntary brain screening and had no cerebrovascular risk factors, such as hypertension, diabetes mellitus, or hyperlipidemia. We examined the conventional and T2-weighted MRI to define white matter hyperintensities, HA, and cerebral microbleeds in addition to all physical parameters, blood biochemical data, and neuropsychiatric symptoms. We found that the prevalence of white matter lesions and HA increased significantly with age (P < .001). Logistic analysis showed that periventricular hyperintensity was significantly related to age (P < .0001) and depressive state (P < .01). A linear relation was found between white matter lesions and HA (P < .05). Cerebral microbleeds also increased with age, and their presence was associated with HA (P < .001). White matter lesions, HA, and cortical microbleeds were associated with one another in healthy elderly subjects, and these changes were affected by the aging process independent of any cerebrovascular risk factors. Cerebral amyloid angiopathy may underlie these age-related brain changes.
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PMID:Age-related changes in white matter lesions, hippocampal atrophy, and cerebral microbleeds in healthy subjects without major cerebrovascular risk factors. 2063 92