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Biomedical subjects

S Malek

Publications and source records attributed to S Malek.

23 records · Page 2Linked to original sources
PubMed1992

Structure of a G.T.A triplet in an intramolecular DNA triplex.

A 32-base DNA oligonucleotide has been studied by one- and two-dimensional 1H NMR spectroscopy and is shown to form a stable, pyr.pur.pyr, intramolecular triple helical structure, with a four C loop and a TATA loop connecting the Watson-Crick- and Hoogsteen-paired strands, respectively. This triplex contains five T.A.T base triplets, two C+.G.C base triplets, and an unusual G.T.A base triplet which disrupts the pyr.pur.pyr motif. The G.T.A triplet consists of a Watson-Crick T.A base pair, with the T situated in the "purine strand" and the A situated in the "pyrimidine strand" and a G situated in the Hoogsteen-base-paired "pyrimidine strand" hydrogen bonded to the T. The base-pairing structure of the G.T.A triplet has been investigated and has been found to involve a single hydrogen bond from the guanine amino group to the O4 carbonyl of the thymine, leaving the guanine imino proton free. The specific amino proton involved in the hydrogen bond is the H2(2) proton. This orients the guanine such that its sugar is near the thymine methyl group. The guanine sugar adopts an N-type (C3'-endo) sugar pucker in this triplet. The stability of the G.T.A triplet within pyr.pur.pyr triplexes is discussed.

Base Composition↗
PubMed1991

Structure and stability of X.G.C mismatches in the third strand of intramolecular triplexes.

Intramolecular DNA triplexes that contain eight base triplets formed from the folding of a single DNA strand tolerate a single X.G.C mismatch in the third strand at acidic pH. The structure and relative stability of all four triplets that are possible involving a G.C Watson-Crick base pair were determined with one- and two-dimensional proton nuclear magnetic resonance techniques. Triplexes containing A.G.C, G.G.C, or T.G.C triplets were less stable than the corresponding parent molecule containing a C.G.C triplet. However, all mismatched bases formed specific hydrogen bonds in the major groove of the double helix. The relative effect of these mismatches on the stability of the triplex differs from the effect assayed (under different conditions) by two-dimensional gel electrophoresis and DNA cleavage with oligonucleotide EDTA.Fe(II).

Base Sequence↗
PubMedDate not supplied

Early organ-specific hemorrhage-induced increases in tissue cytokine content: associated neurohormonal and opioid alterations.

Hemorrhage is associated with an impairment in the immune response and with increased concentrations of circulating inflammatory cytokines. The present study determined the time course and localization of alterations in circulating and tissue pro-inflammatory cytokines (TNF-alpha, IL-1-alpha and -beta) in response to fixed-pressure (40 mm Hg) hemorrhage as well as the associated hanges in circulating neurohormonal and opioid mediators. Conscious unrestrained non-heparinized male Sprague-Dawley rats (n = 24) underwent hemorrhage followed by standard resuscitation with lactated Ringer's solution. Animals were sacrificed at three time points; immediately after the hemorrhage period, at completion of resuscitation and 1.5 h after the resuscitation period. Hemorrhage resulted in marked elevations in circulating levels of TNF-alpha, which averaged 860 +/- 201 pg/ml. The levels were similarly elevated following fluid resuscitation (877 +/- 196 pg/ml) and had decreased towards baseline 1.5 h after completion of resuscitation (281 +/- 134 pg/ml). TNF-alpha was not detectable in plasma of time-matched controls. Hemorrhage elevated TNF-alpha content in spleen (25%), lung (55%) and heart (20%), and tissue content remained elevated despite resuscitation. No significant changes in tissue content of TNF-alpha were detected in the liver, kidney or brain. Circulating levels of IL1-alpha and -beta were not detectable in either the time-matched controls or hemorrhaged animals. However, statistically significant elevations in tissue content of IL-1 alpha were observed in heart, spleen, lung, gut and whole brain (15-30%). Tissue content of IL-1 beta did not change in response to hemorrhage and/or fluid resuscitation. Activation of sympathetic outflow, as evidenced by a 3- to 4-fold elevation in circulating epinephrine and norepinephrine levels, was observed immediately after hemorrhage, and was associated with a 5-fold rise in circulating beta-endorphin. These results demonstrate an early increase in tissue cytokine content following hemorrhagic shock, which is associated with elevations in circulating catecholamines and endogenous opioids, consistent with their potential modulatory role in this response.

Animals↗