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Biomedical subjects

C A Bush

Publications and source records attributed to C A Bush.

At least 91 records · Page 5Linked to original sources

Identification and fractionation of human milk oligosaccharides by proton-nuclear magnetic resonance spectroscopy and reverse-phase high-performance liquid chromatography.

It has been shown that the retention times of oligosaccharides containing N-acetyl amino sugars in reverse-phase high-performance liquid chromatography are sensitive both to chain length and to stereochemical differences. Data showing that oligosaccharides of human milk can be fractionated according to stereochemistry on C-18 columns using water as eluant, is presented. Detection at the nanomolar level is possible using ultraviolet absorption at 190 nm as a result of the acetamido group. The separation of linkage isomers by fractionation of two tetrasaccharides of identical carbohydrate composition, lacto-N-tetraose and lacto-N-neotetraose, and by the separation of two isomeric pentasaccharides, lacto-N-fucopentaose I and II, is shown. In some cases it was possible to preparatively fractionate pure oligosaccharides from complex mixtures. The identity and purity of the oligosaccharides was determined by proton-nuclear magnetic resonances spectroscopy at 300 MHz using the method of Vliegenthart and co-workers (B. Fournet, G. Montreuil, L. Strecker, J. Dorland, J. Haverkamp, J. F. G. Vliegenthart, J. P. Binette, and K. Schmid (1978) Biochemistry 17(24), 5206; J. F. G. Vliegenthart, H. V. Halbeek, and L. Dorland (1981) Pure Appl. Chem. 53, 45) in which "structural reporter" protons are identified for the different isomeric oligosaccharides. In addition to assignment of the anomeric proton resonances, it was possible to assign H4 of galactose linked at O3 as well as fucose H5 and H6 resonances.

Chemical Phenomena↗

Monte Carlo calculations on the conformations of models for the glycopeptide linkage of glycoproteins.

In order to search for probable conformations of the peptide, the amino acid side chain, and the carbohydrate linkage in glycoproteins, conformational energy surfaces of glycopeptide model compounds were studied by Monte Carlo methods using the Metropolis algorithm. The potential energies were composed of empirical energy functions which include nonbonded interactions, electrostatics, hydrogen bonding, and torsional energies specified by parameters which have been used for peptides. Calculations were performed on 1-N-acetyl-2-acetamido-beta-D-glucopyranosyl amine and the glycosylated dipeptide N-acetyl-delta-N-(2-acetamido-beta-D-glucopyranosyl)-L-asparaginyl-N'-methyl amide as models for N-glycosylated peptides and on methyl-2-acetamido-alpha-D-galactopyranoside as well as the glycosylated dipeptides N-acetyl-gamma-O-(2-acetamido-alpha-D-galactopyranosyl)-L-threonyl-N'-methyl amide and its seryl analog as models for O-glycosylated glycoproteins. The probable conformations of these compounds were analyzed by single-angle probability tables and by two-dimensional conformation density maps projected from the Markov chains which contained up to six independently varied conformational dihedral angles. The presence of high barriers to rotation required the use of search strategies which resulted in a rather low acceptance rate for new conformations in the Metropolis algorithm in order to avoid trapping of the Markov chain in local energy minima. This problem contributed to the failure of these calculations to attain complete convergence to the thermodynamic limit for the glycosylated dipeptide models in which six dihedral angles were independently varied. Analysis of the results shows that the conformational space available to the highly crowded axial glycosides of the alpha-O-GalNAc type is much more restricted than that for the N-asparaginyl glycopeptides. The most probable conformation for the O-glycosylated peptides is is a beta-turn while N-glycosylated peptides may be either in a beta-turn or an extended conformation.

Glycopeptides↗

Assessment of ventricular function by combined noninvasive measures: factors accounting for methodologic disparities.

We studied the predictive accuracy and disparities among cineventriculographic ejection fraction, pre-ejection period over left ventricular ejection time (PEP/LVET) obtained from the systolic time intervals and the percent shortening of the internal echocardiographic diameter (% delta D) in assessing left ventricular performance in 453 consecutive patients without valvular heart disease. In 308 patients all three tests were normal, and in 78 patients all three tests were abnormal. Overall agreement (predictive accuracy) among ejection fraction (normal greater than or equal to 57), % delta D (normal greater than or equal to 28%) and PEP/LVET (normal less than or equal to 0.42) was 85%. In 67 patients disparities among the tests as measures of global left ventricular performance were found. The major mechanisms accounting for such disparities were: (a) large segmental contraction abnormalities which selectively distort the % delta D and ejection fraction and (b) diminished isovolumic pressure (less than 45 mmHg) which distorts PEP/LVET. When patients with segmental contraction abnormalities and low isovolumic pressure were excluded the agreement between PEP/LVET and ejection fraction was 97%, ejection fraction and % delta D 98% and PEP/LVET and % delta D 97%. The combined uses of systolic time intervals and echocardiogram minimizes error due to segmental contraction abnormalities and isovolumic pressure. If both PEP/LVET and % delta D are concordant the agreement with ejection fraction is 94% for normal and 99% for abnormal left ventricular function.

Adult↗

Assessment of left ventricular pressure-volume relations using gated radionuclide angiography, echocardiography, and micromanometer pressure recordings. A new method for serial measurements of systolic and diastolic function in man.

This study was designed to validate the use of combined invasive and noninvasive methods in assessing serial pressure-volume relations in man. Ten patients undergoing cardiac catheterization were studied with simultaneous intracardiac micromanometer pressure recordings, gated radionuclide angiography and echocardiography. Systolic and diastolic function were measured at rest, during right atrial pacing rates of 100 and 120 beats/min and after nitroglycerin administration. Right atrial pacing studies (rate of 100 beats/min) were performed in duplicate to determine the reproducibility of the method. At the conclusion of each study, the model was validated with contrast angiography. Good reproducibility was evident when measuring the maximum and average filling and ejection rates, time to peak filling rate, ejection fraction, the modulus of chamber stiffness, the time course of left ventricular relaxation, global average stress and ventricular work indexes using the model described above. These data were not significantly different (p greater than 0.05) from comparable data obtained from contrast angiography. Right atrial pacing and nitroglycerin administration resulted in predictable alterations in the pressure-volume loop and in the systolic and diastolic measurements. The maximum and average filling rates, ejection rates and time to peak filling rate appeared to be heart rate-dependent variables. By combining available invasive and noninvasive methods, accurate pressure-volume relationships can be determined. Because the method we tested provides accurate volumetric and timing measurements for cardiac events and does not alter hemodynamics, it may be useful for obtaining serial assessments of the pressure-volume relationship in man.

Adult↗

Conformation of the complex oligosaccharides of glycoproteins. A vacuum ultraviolet circular dichroism study.

Circular dichroism spectroscopy in the 170-220-nm range of the ultraviolet and measurements of the amide proton coupling constants in nmr have been used to investigate the conformation of asparagine-linked glycopeptides having oligosaccharide chains of the complex antenna type. The CD spectra can be explained as the sum of three contributions, the first of which is a pair of large bands of opposite sign resulting from coupling of the adjacent chromophores of the 2-acetamido-1-N-(4-aspartyl)-2-deoxy-beta-D-glucopyranosylamine linkage. Secondly the amide chromophore of the core N-acetylglucosamine residue substituted at carbon 4 by a beta-mannosyl residue contributes a negative band at 210 nm along with a small negative signal in the 180-190-nm region. The amides of the antenna N-acetylglucosamine residues, which in some cases are substituted by beta-galactosyl residues at carbon 4, contribute a negative band at 210 and a strong positive band at 185-190 nm. Since these three contributions are approximately independent, we can detect no long range interactions between nonreducing termini and the glycopeptide linkage region. Both CD and nmr data imply that the glucosaminyl-asparagine linkage is rigidly fixed in a conformation having the amide protons trans to the sugar ring protons. These results are consistent with an extended conformation in the shape of a "Y" or a "T" for complex type asialo-oligosaccharide chains.

Carbohydrate Conformation↗

Long-term survival following cardiac rupture with subsequent development of left ventricular pseudoaneurysm.

This report describes a patient who survived rupture of the left ventricular free wall following a myocardial infarction and who then subsequently went on to develop a pseudoaneurysm. The rupture became clinically recognized when the patient developed cardiac tamponade. A large hemopericardium was evacuated by performing a thoracotomy and a pericardiotomy. Although not evident at the time of the initial catheterization, a pseudoaneurysm developed over the ensuing months. The aneurysm was initially recognized by radionuclide angiography and confirmed by left ventricular angiography at a second cardiac catheterization. The aneurysm was successfully resected, and the patient was alive and functioning normally 18 months after rupture and 12 months after aneurysmectomy.

Aged↗

Methacholine provocation of Prinzmetal's variant angina pectoris: a revised perspective.

We report 13 patient with unequivocal Prinzmetal's variant angina pectoris as the entire experience with this syndrome during a 7-year period in a single institution. The clinical diagnosis of this relatively uncommon disorder is emphasized. Five patients were given 10 mg of methacholine subcutaneously. Three demonstrated subsequent delayed appearance of chest pain, ECG change, and coronary vasospasm following early appearance of muscarinic effects. Two Prinzmetal patients had no provocation of variant angina following methacholine, though they did experience significantly less blood pressure fall in response to muscarinic provocation. Another 23 subjects with incompletely explained chest pain given methacholine had neither ECG change nor spasm. Methacholine provocation of variant angina need not necessarily implicated a parasympathomimetic mechanism for otherwise spontaneous episodes. Rather, provocation would appear to occur via the customary reflex adrenergic response to drug-induced hypotension. Methacholine is probably safe though unreliable as an agent to be used for spasm provocation.

Adult↗

The anatomic relationship of the esophageal lead to the left atrium.

This study was undertaken to establish the "in vivo" anatomic relationship of the esophageal catheter to the left atrium. Fourteen patients, seven of whom had enlarged left atria, were included in the study. During cardiac catheterization, a bipolar recording catheter was placed in the esophagus; left atrial cineangiograms were then obtained in the posterior-anterior (PA), left anterior oblique (LAO), and lateral views. The distance of the esophageal catheter, in each of four commonly used positions, to the interatrial septum-right atrium was measured in the PA and LAO cineangiograms. The distance from the same catheter positions to the posterior left atrial wall was measured from the lateral view. In all positions and regardless of left atrial size, the catheter clearly lay behind the left atrium and was closer to the left atrial wall than any other cardiac structure, including the interatrial septum. Bipolar electrograms were recorded from the four commonly used esophageal locations; atrial wave amplitude and other parameters of the electrogram deflection did not vary significantly in the different lead positions. We conclude that esophageal electrograms reflect left atrial activity by virtue of the recording electrode's clear proximity to this structure. The amplitude and configuration of the atrial wave itself is generally not useful in determining the position of the esophageal lead.

Adult↗

Antifreeze glycoprotein. Conformational model based on vacuum ultraviolet circular dichroism data.

Circular dichroism spectra (CD) of an active fraction of antifreeze glycoprotein (AFGP) and of a lower molecular weight fraction which is less active are found to be similar in the wavelength range 170-230 nm. The contribution of the disaccharide side chain chromophores to the CD spectra of the glycoprotein is estimated from spectra of model oligosaccharides having similar structures. Comparison of the CD spectra of the peptide portion of AFGP to those of established model polypeptides suggests a 3-fold left-handed helix of the collagen type as the most likely conformation of the peptide. In the proposed model, the disaccharide moieties attached to every third residue are in identical environments. Furthermore, proline residues which are found in the less active fraction can be accommodated in this helical structure, consistent with the observed similarity of the spectra of the two fractions.

Antifreeze Proteins↗