Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0162871 (abdominal aortic aneurysm)
 8,664 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Although elastin depletion is thought to be an etiologic factor in abdominal aortic aneurysm, little is known about its transcription and posttranslational modification in normal and diseased human aorta. Our objectives were to quantify total elastin and elastin cross-links (desmosine/isodesmosine [DID]) and to determine if elastin mRNA was detectable in the disease-prone infrarenal aorta from patients with abdominal aortic aneurysm and a comparative group with no aneurysmal diseases. After preliminary extraction and thermolysin digestion, content of DID and the elastin tetrapeptide, valine-alanine-proline-glycine (VAPG), were determined by high-performance liquid chromatography. Tissue mRNA was studied by Northern blot analysis. Mean values (+/- SE) were compared by Student's t test. The proportion of insoluble elastin was markedly decreased in abdominal aortic aneurysm tissue (1.3% +/- 0.04% vs 12% +/- -2.8%; p less than 0.001). There was no difference in the small percentage of elastin solubilized during extraction in abdominal aortic aneurysm (5.3% +/- 1%) and no aneurysmal disease (6.0% +/- 1.2%; p = 0.71) tissues. The DID concentration of insoluble elastin was not different for abdominal aortic aneurysm and no aneurysmal disease tissue (0.18% +/- 0.07 vs 0.18 +/- 0.05 nm DID/nm VAPG; p = 0.97). On the basis of VAPG content, only 26% +/- 4% of the sodium hydroxide insoluble residue from abdominal aortic aneurysm was elastin; the predominate protein(s) was high in polar amino acids. Elastin mRNA was detectable in all tissues.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Elastin content, cross-links, and mRNA in normal and aneurysmal human aorta. 149 42

An analogue of Hoechst 33258, bearing a phenolic hydroxyl group in the meta rather than para position, was designed using molecular graphics to introduce hydrogen-bonding potentials between this OH group and the C = O group of cytosine-9 and the NH2 group of guanine-4', of the opposite strand of the B-DNA duplex, d(CGCGAATTCGCG)2. This derivative (meta-Hoechst) was synthesized in seven steps and characterized. Its binding to DNA was assessed by measurements of melting temperatures (Tm) and found to be similar in strength and AT preference to the parent Hoechst 33258 at this gross level. The AT preference of meta-Hoechst and Hoechst 33258 was probed further using hydroxyl radical footprinting on the tyrT DNA fragment, for which clear footprints were detected at AAT, AAA and ATAT runs, as for netropsin and distamycin. Hydroxyl radical footprinting was carried out on a trimer of CGCGAATTCGCG cloned into a longer DNA fragment, for which clear footprints for both Hoechst 33258 and meta-Hoechst were detected in regions with four or more contiguous AT base pairs. Three cell lines derived from haematological malignancies were more sensitive to both Hoechst 33258 and meta Hoechst than lines derived from solid tumours, but there was no significant difference between the activity of these two Hoechst derivatives.
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PMID:Synthesis, DNA binding, footprinting and in vitro antitumour studies of a meta-hydroxy analogue of Hoechst 33258. 757 88