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At least 199 records · Page 11Linked to original sources

Halting the progression of atherosclerosis with intensive lipid lowering: results from the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) trial.

Intravascular ultrasonography is a catheter-based technique used to provide 3-dimensional views of the vessel lumen as well as the size and distribution of atherosclerotic plaques. This imaging technique was used in the Reversal of Atherosclerosis with Aggressive Lipid Lowering (REVERSAL) study, an 18-month, randomized, controlled, multicenter trial comparing the effects of intensive versus moderate lipid-lowering therapy on plaque progression in patients requiring coronary angiography. A total of 253 patients were randomized to atorvastatin 80 mg/day (intensive lipid lowering) and 249 patients were randomized to pravastatin 40 mg/day (moderate lipid lowering). Low-density lipoprotein (LDL) cholesterol levels decreased from a baseline mean of 150 mg/dL (3.9 mmol/L) in both groups to 79 mg/dL (2.0 mmol/L) in the atorvastatin group and 110 mg/dL (2.9 mmol/L) in the pravastatin group. High-sensitivity C-reactive protein (hs-CRP) levels decreased by 36.4% in the atorvastatin group versus 5.2% in the pravastatin group (P <0.001). For the primary end point of percent change in total atheroma volume, a significantly lower rate of progression from baseline was observed with atorvastatin (-0.4%) than with pravastatin (2.7%) (P = 0.02). Linear regression analysis showed an inverse relation between lipid reduction and plaque progression for both groups; however, at any given level of LDL cholesterol, the progression rate was lower with atorvastatin compared with pravastatin. Both regimens were well tolerated. The results show that intensive lipid lowering with atorvastatin 80 mg/day for 18 months halted the progression of coronary atherosclerosis, whereas more moderate lipid lowering with pravastatin 40 mg/day was associated with progression. The differences in the progression rate are likely to be a result of greater reduction in atherogenic lipoproteins and hs-CRP with intensive therapy.

Atherosclerosis↗

Sequence reversed peptide from CaMKK binds to calmodulin in reversible Ca2+ -dependent manner.

Calmodulin (CaM) is a highly versatile Ca(2+) signaling transducer known to regulate over a hundred proteins. In this paper, we further demonstrate the versatility of CaM binding by showing that it binds to a synthetic peptide (revCKKp) made by reversing the amino acid sequence of the CaM-binding peptide (CKKp) from CaM-dependent protein kinase kinase (CaMKK) (residues 438-463). Sequence comparison between revCKKp and other CaM-binding peptides (CBPs) from the CaM target databank showed that revCKKp does not resemble any existing classes of CBPs, except CKKp [M. Zhang, T. Yuan, Molecular mechanisms of calmodulin's functional versatility, Biochem. Cell Biol. 76 (1998) 313-323; S.W. Vetter, E. Leclerc, Novel aspects of calmodulin target recognition and activation, Eur. J. Biochem. 270 (2003) 404-414]. Furthermore, computational modeling showed that revCKKp could bind CaM in a similar manner to CKKp. Lastly, we experimentally showed that our synthetic revCKKp binds to CaM in a reversible Ca(2+)-dependent manner.

Amino Acid Sequence↗

Reversible reaction of 5,5'-dithiobis(2-nitrobenzoate) with the CysF9[93]beta sulfhydryl groups of the hemoglobins of the domestic cat: variation of the equilibrium and reverse rate constants with pH.

We have determined for the first time the equilibrium constant, Keq, for the reaction of Ellman's reagent, 5,5'-dithiobis(2-nitrobenzoate), with the CysF9[93]beta sulfhydryl groups of the hemoglobins of the domestic cat. In the pH range 5.6 to 9.0 Kequ varies over four orders of magnitude--between ca 10 and 10(-3)--for all hemoglobin derivatives. Using these Kequ values and published data on the dependence of the apparent second order forward rate constant, kf, on pH we have calculated the apparent second order reverse rate constant, kr, as a function of pH. This parameter increases strongly with pH, particularly above pH 7.5. Quantitative analyses of the pH dependence profiles of log10kr indicate that the reverse reaction is coupled to the ionization of two groups on the protein with pKas of 7.2+/-0.2 and 9.4+/-0.1 in the major hemoglobin and 6.7+/-0.3 and 8.4+/-0.1 in the minor hemoglobin.

Animals↗

Comprehensive two-dimensional separations of complex mixtures using reversed-phase reversed-phase liquid chromatography.

A comprehensive two-dimensional reversed-phase reversed-phase liquid chromatographic system for the separation of a complex mixture of oligostyrenes was developed using results from a previous theoretical assessment of the informational similarity, percent synentropy, orthogonality and peak capacity of hypothetically coupled systems. The degree of sample attribute order in the first separation dimension was also used in the development of the experimental two-dimensional system. A C18(methanol)/CCZ(acetonitrile) two-dimensional system was chosen for the comprehensive analysis of the oligostyrene mixtures because this system had the lowest solute crowding, highest orthogonality and was observed to have order with respect to a sample attribute in the first separation dimension. The separations achieved were in full agreement with the results from information theory and (a geometric approach to) factor analysis assessments. High sampling rates in the first liquid chromatographic dimension were shown to be impossible or inefficient when the peak capacity and separation time of the second dimension was high or when the aim of the exercise was to isolate individual sample constituents in high yield.

Chromatography, Liquid↗

EXAFS studies on adsorption-desorption reversibility at manganese oxide-water interfaces. II. Reversible adsorption of zinc on delta-MnO2.

Microscopic structures of Zn(II) adsorbed at delta-MnO(2)-water interfaces were studied using extended X-ray absorption fine structure (EXAFS) spectroscopy. In a 0.1 M NaNO(3) solution of pH 5.50, hydrous Zn(II) was adsorbed onto the solid surface in the form of octahedral coordination. Adsorbed octahedral Zn(II) was located above and below the vacancy sites of delta-MnO(2). Each Zn was coordinated on one side to H(2)O molecules forming an H(2)O sheet and on the other side to oxygen atoms shared with layer MnO(6) octahedra forming a corner-sharing octahedral interlayer complex. The average Zn-O and Zn-Mn distances were 2.07+/-0.01 and 3.52+/-0.01 A, respectively. Macroscopic adsorption-desorption isotherms showed that, in contrast to that of the Zn-gamma-MnOOH system, adsorption of Zn(II) on delta-MnO(2) was highly reversible. EXAFS results indicated that the highly reversible adsorption was due to the weak adsorption mode of the corner-sharing linkage between the adsorbate and adsorbent polyhedra.

Journal Article↗

Isolation of pituitary peptides by reversed-phase high-performance liquid chromatography. Expansion of the resolving power of reversed-phase columns by manipulating pH and the nature of the ion-pairing reagent.

The reversed-phase liquid chromatographic behaviour of pituitary peptides at various pH values was compared. The retention times of peptides at pH 1, 3 and 4.5 were essentially as expected for acidic solvent systems. However, at pH 5.5 or 7, radically different elution characteristics were observed. This is probably brought about by the increase in polarity that accompanies ionization of the peptide carboxyl groups at higher pH values. Basic hydrophobic ion-pairing reagents, such as tetrabutylammonium ion, can be used to maximize differences in polarity. We have previously shown that the use of acidic hydrophobic ion-pairing reagents at low pH (e.g. trifluoroacetic and heptafluorobutyric acids) enhances the basic polarity of peptides. The combination of both approaches facilitated the reversed-phase purification of posterior pituitary glycopeptide and alpha-N-acetyl-beta-endorphin1-27 from an extract of 200 rat neurointermediate pituitaries. The separation of these two peptides at low pH, which is particularly difficult, was achieved by the sequential use of solvent systems containing trifluoroacetic acid (0.1%), heptafluorobutyric acid (0.13%) and finally triethylamine acetate (0.01 M, pH 5.5).

Animals↗

Two dimensional reversed-phase-reversed-phase separations isomeric separations incorporating C18 and carbon clad zirconia stationary phases.

Informational theory and a geometric approach to factor analysis were employed to evaluate the degree of orthogonality of a two-dimensional reversed-phase-reversed-phase chromatographic system. The system incorporated a C18 column as one dimension and a carbon clad zirconia column as the second dimension. In order to study the resolving power of this system, the separation of a sample matrix containing an artificial mix of 32 isomers (structural and diastereoisomers) was evaluated. Using this system, between 25 and 28 of the 32 isomers could be separated, depending on the mobile phase combinations--with resolution that could not possibly be achieved in a single one dimensional separation. The results from this study indicate that in order to fully evaluate the resolving power of a 2D system multiple methods of analysis are most appropriate. This becomes increasingly important when the sample contains components that are very closely related and the retention of solutes is clustered in one quadrant of the 2D space. Ultimately, the usefulness of the 2D separation is determined by the goals of analyst.

Carbon↗

Evaluation of the two-dimensional reversed-phase-reversed-phase separations of low-molecular mass polystyrenes.

The resolving power of four reversed-phase-reversed-phase two-dimensional (2D) chromatographic systems was evaluated using information theory (IT) and a geometric approach to factor analysis. The first separation dimension employed a C18 column, while the second separation dimension employed a carbon clad zirconia column. Mobile phases in each dimension were either methanol or acetonitrile. The sample matrix that was employed in this study contained a mixture of 58 components, comprised of stereoisomers and structural isomers of a systematic variation in molecular weight. Each of the components were oligostyrenes, with between two and five configurational repeating units having either n-butyl, sec-butyl or tert-butyl end groups. In the two-dimensional systems employed in this study, between 46 and 49 of the 58 components could be separated, depending on the mobile phase combinations--with apparent resolution that could not possibly be achieved in a single one-dimensional separation. The results from this study indicate that in order to fully evaluate the resolving power of a 2D system multiple methods of analysis that evaluate the separation potential are most appropriate. This becomes increasingly important when the sample contains components that are very closely related and the retention of solutes displays a high degree of solute crowding.

Molecular Weight↗

Comparison of reversed phase and reversed phase ion pair high performance liquid chromatography for analysis of TcO and TcN complexes of L,L-ethylene dicysteine di-ethylester and its acid analogues.

99mTc(V)-oxo complexes of L,L-ethylene dicysteine (L,L-EC) and its di-ester derivative L,L-ethyl cysteinate dimer (L,L-ECD) are useful tracer agents for evaluation of renal function and cerebral blood flow respectively. Labelling of these molecules with a 99mTc(V)-nitrido core instead of the 99mTc(V)-oxo core alters their biological and physiochemical behavior. In the reversed phase high performance liquid chromatography (HPLC) method presently used to analyse 99mTc(V)-oxo preparations of L,L-EC and L,L-ECD, the 99mTc(V)-nitrido-L,L-EC complex and the possible impurities of a 99mTc(V)-nitrido-L,L-ECD preparation were found to elute with the void volume. In this study, a reversed phase ion pair HPLC method has been developed that is useful for the analysis of both 99mTc(V)-oxo and 99mTc(V)-nitrido preparations of L,L-EC and L,L-ECD. Tetrabutylammonium hydroxide is used as a cationic ion pairing agent.

Chromatography, High Pressure Liquid↗

Combination reversed and non-reversed upper arm vein for femoro-distal grafting.

Arm veins are the "second choice" conduit for femoro-distal grafting when the long saphenous vein is either not available or is unsuitable. However, obtaining a graft of sufficient length may be difficult if the forearm veins have been damaged by previous intra-venous cannulation. The harvesting of the upper arm veins separately may overcome the problem of insufficient length but entails a veno-venous anastomosis which is a potential source of both early and late problems. We have harvested both the upper arm cephalic and basilic veins in continuity and created a vein graft which is non-reversed proximally and reversed distally.

Aged↗

Ligand Effects in the Models and Mimics of Oxyhemocyanin and Oxytyrosinase. A Density Functional Study of Reversible Dioxygen Binding and Reversible O-O Bond Cleavage.

We studied the energetics of dioxygen binding and the core isomerization between the Cu(2)(&mgr;-eta(2):eta(2)-O(2)) and Cu(2)(&mgr;-O)(2) core structures of {[LCu](2)O(2)}(2+), L = 1,4,7-triazacyclononane (1) and L = hydrotris(pyrazolyl)borate (2), by gradient-corrected density functional methods. N-Substituted derivatives of 1 and 2 are synthetic inorganic mimics of oxyhemocyanin with similar physical and spectroscopic properties but different chemical behavior. The calculated dioxygen binding energies of 1 and 2 are -60 and -184 kJ/mol, respectively, in line with the observation that 1 binds oxygen reversibly and 2 does so irreversibly. Bond energy decomposition showed that orbital interactions contribute equally to the binding energy of 1 and 2, which explains the similarities in their spectral properties. Electrostatic interactions due to the negatively charged ligand are responsible for stronger binding in 2. The core isomerization energies for isomerization from the Cu(2)(&mgr;-eta(2):eta(2)-O(2)) to the Cu(2)(&mgr;-O)(2) isomers of 1 and 2 are +1 and +12 kJ/mol, respectively. The barrier heights of the core isomerizations of 1 and 2 relative to the Cu(2)(&mgr;-eta(2):eta(2)-O(2)) isomer are 33 and 37 kJ/mol, respectively. The results on 1 are in line with the experimentally observed fast and reversible interconversion between the two isomers while these data on 2 suggest that the observation of 2 in the (&mgr;-O)(2) isomer was only prevented by its thermal instability. We also considered a purely theoretical model compound, {[(NH(3))(3)Cu](2)O(2)}(2+) (3). Calculations on 3 show that this model is clearly inadequate even for qualitative energetic modeling of dioxygen binding while it is successful in describing spectral, structural, and magnetic properties. Calculations show that the isomerization of 3 is endoergic by 49 kJ/mol, and there is essentially no energy barrier relative to the higher energy (&mgr;-O)(2) isomer. The dioxygen binding energy of 3 is endoergic by 160 kJ/mol as opposed to the exoergic binding in both 1 and 2.

Journal Article↗

Orientation-reversal and phase-reversal visual evoked potentials in full-term infants with brain lesions: a longitudinal study.

The onset and maturation of visual cortical mechanisms can be recorded by using steady-state visual evoked potentials. The aim of this study was to evaluate and compare orientation-reversal (OR) and phase-reversal (PH) VEP as indicators of the maturation of cortical function in a population of fullterm infants with brain lesions on neonatal MRI. Forty-six infants with brain lesions on neonatal MRI were tested on both PH and OR VEP at 8 reversals/second at the age of 5 months and, if the responses were not significant, at a lower temporal frequency (4 reversals/second). Children whose VEPs were not significant at 5 months were tested longitudinally at 6, 9, 12 and 18 months. The results showed that 23 of the 46 infants (50%) did not show significant responses at 5 months and that while in 7 of the 23 (14% of the whole cohort) the responses became significant between 5 and 12 months, in the other 16 infants (34%) the VEP responses were persistently abnormal. Children with focal lesions, such as focal infarction or haemorrhages, tended to show normal or only mildly delayed VEP while more generalised lesions, such as the ones seen in infants with hypoxic-ischaemic encephalopathy grade 2 and 3, tended to be associated with abnormal VEP responses. The involvement of the optic radiations and occipital cortex was not always associated with abnormal VEP responses but the concomitant involvement of the basal ganglia was always associated with abnormal VEP. We were also able to demonstrate that VEP can be also used as a prognostic indicator: while normal OR VEP are reliably associated with a normal visual and neurodevelopmental outcome, abnormal 4 OR or 8 PH at 5 months are consistently associated with abnormal outcome.

Brain Diseases↗

Reversible cerebral hypoperfusion observed with Tc-99m HMPAO SPECT in reversible dementia caused by hypothyroidism.

A 69-year-old man had hypothyroid dementia as a result of I-131 therapy and an overdose of methimazole. Tc-99m HMPAO SPECT revealed diffuse cerebral hypoperfusion. The findings of brain SPECT normalized with the disappearance of symptoms and a return to the euthyroid state. There was a 25% or 26% reduction of the mean cerebral blood flow during dementia. This may be the first report in which SPECT brain imaging revealed reversible hypoperfusion associated with reversible hypothyroid dementia.

Aged↗

Transport barrier inside the reversal surface in the chaotic regime of the reversed-field pinch.

Magnetic field lines and the corresponding particle orbits are computed for a typical chaotic magnetic field provided by a magnetohydrodynamics numerical simulation of the reversed-field pinch. The m = 1 modes are phase locked and produce a toroidally localized bulging of the plasma which increases particle transport. The m = 0 and m = 1 modes produce magnetic chaos implying poor confinement. However, they also allow for the formation of magnetic islands which induce transport barriers inside the reversal surface.

Journal Article↗

Reverse transcriptase in archaebacteria. Purification and characterization of a primase-reverse-transcriptase complex from Halobacterium halobium.

A primase-reverse-transcriptase of Halobacterium halobium was purified by column chromatography on DEAE-cellulose, hydroxyapatite and carboxymethyl-cellulose, followed by sedimentation on a glycerol gradient. The enzyme is a multifunctional enzyme containing reverse transcriptase. DNA polymerase and RNase H activities and does not require a performed primer to initiate DNA synthesis. Using a single-stranded DNA as template, this enzyme synthesizes oligonucleotides (8-12 bases) that can be used a primer by Escherichia coli DNA nucleotidyltransferase I (DNA polymerase I, Klenow fragment). Two polypeptides of 67 and 57 kDa were found after 14750-fold purification of the enzyme.

Chromatography↗

Efficient RNA ligation by reverse-joined hairpin ribozymes and engineering of twin ribozymes consisting of conventional and reverse-joined hairpin ribozyme units.

In recent years major progress has been made in elucidating the mechanism and structure of catalytic RNA molecules, and we are now beginning to understand ribozymes well enough to turn them into useful tools. Work in our laboratory has focused on the development of twin ribozymes for site-specific RNA sequence alteration. To this end, we followed a strategy that relies on the combination of two ribozyme units into one molecule (hence dubbed twin ribozyme). Here, we present reverse-joined hairpin ribozymes that are structurally optimized and which, in addition to cleavage, catalyse efficient RNA ligation. The most efficient variant ligated its appropriate RNA substrate with a single turnover rate constant of 1.1 min(-1) and a final yield of 70%. We combined a reverse-joined hairpin ribozyme with a conventional hairpin ribozyme to create a twin ribozyme that mediates the insertion of four additional nucleotides into a predetermined position of a substrate RNA, and thus mimics, at the RNA level, the repair of a short deletion mutation; 17% of the initial substrate was converted to the insertion product.

Base Sequence↗

Extreme reversed sexual dichromatism in a bird without sex role reversal.

Brilliant plumage is typical of male birds, reflecting differential enhancement of male traits when females are the limiting sex. Brighter females are thought to evolve exclusively in response to sex role reversal. The striking reversed plumage dichromatism of Eclectus roratus parrots does not fit this pattern. We quantify plumage color in this species and show that very different selection pressures are acting on males and females. Male plumage reflects a compromise between the conflicting requirements for camouflage from predators while foraging and conspicuousness during display. Females are liberated from the need for camouflage but compete for rare nest hollows.

Adaptation, Biological↗

Determinants of arterial wall remodeling during lipid-lowering therapy: serial intravascular ultrasound observations from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial.

BACKGROUND: Coronary plaque progression and instability are associated with expansive remodeling of the arterial wall. However, the remodeling response during plaque-stabilizing therapy and its relationship to markers of lipid metabolism and inflammation are incompletely understood. METHODS AND RESULTS: Serial intravascular ultrasound (IVUS) data from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial were obtained during 18 months of intensive versus moderate lipid-lowering therapy. In a subgroup of 210 patients, focal coronary lesions with mild luminal narrowing were identified. Lumen area, external elastic membrane (EEM) area, and plaque area were determined at the lesion and proximal reference sites at baseline and during follow-up. The remodeling ratio (RR) was calculated by dividing the lesion EEM area by the reference EEM area. The relationship between the change in remodeling, change in plaque area, lipid profile, and inflammatory markers was examined. At the lesion site, a progression in plaque area (8.9+/-25.7%) and a decrease in the RR (-3.0+/-11.2%) occurred during follow-up. In multivariable analyses, the percentage change in plaque area (P<0.0001), baseline RR (P<0.0001), baseline lesion lumen area (0.019), logarithmic value of the change in high-sensitivity C-reactive protein (P=0.027), and hypertension at baseline (P=0.014) showed a significant, direct relation with the RR at follow-up. Lesion location in the right coronary artery (P=0.006), percentage change in triglyceride levels (P=0.049), and age (P=0.037) demonstrated a significant, inverse relation with the RR at follow-up. Changes in LDL cholesterol, HDL cholesterol, and treatment group demonstrated no significant associations. CONCLUSIONS: Constrictive remodeling of the arterial wall was observed during plaque-stabilizing therapy with statin medications and appears related to their antiinflammatory effects.

Adaptation, Physiological↗