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M K Dowd

Publications and source records attributed to M K Dowd.

7 recordsLinked to original sources
PubMed1994

Relaxed-residue conformational mapping of the three linkage bonds of isomaltose and gentiobiose with MM3 (92).

Isoenergy surfaces were calculated for the alpha- and beta-anomers of isomaltose and gentiobiose, based on 46,656 conformers for each disaccharide. Low-energy regions exist for each of the three staggered positions about the C-5'-C-6' bonds, and known crystal structures lie in two of these regions. As expected, the molecular partition function showed greater flexibility for these three-bond-linked disaccharides than for comparable two-bond-linked structures. A model miniature crystal of gentiobiose accounts for most of the remaining structural differences between the modeled isolated molecule and the crystal structure. Based on models of isolated molecules of isomaltose and gentiobiose, the predicted Boltzmann-weighted nmr coupling constants were satisfactory, as were predicted optical rotations for gentiobiose.

Carbohydrate Conformation↗
PubMed1992

Conformational analysis of the anomeric forms of sophorose, laminarabiose, and cellobiose using MM3.

Relaxed-residue energy maps based on the MM3 force-field were computed for relative orientations of the pyranosyl rings of sophorose, laminarabiose, and cellobiose, respectively the (1----2)-beta-; (1----3)-beta-; and (1----4)-beta-linked D-glucosyl disaccharides. Sixteen starting conformations of the rotatable exocyclic side-groups were considered for each molecule. All of the energy surfaces have two intersecting low-energy troughs and illustrate the importance of exo-anomeric effects in determining disaccharide conformation. Local minima were found by relaxed minimization without restriction. The energy surfaces of these disaccharides are very similar to the energy surfaces of their corresponding 6-methyltetrahydropyran analogues. There is good agreement between disaccharide structures having minimal MM3 energy and those found by crystallography.

Carbohydrate Conformation↗
PubMed1992

Conformational analysis of the anomeric forms of kojibiose, nigerose, and maltose using MM3.

Energy surfaces were computed for relative orientations of the relaxed pyranosyl rings of the two anomeric forms of kojibiose, nigerose, and maltose, the (1----2)-alpha, (1----3)-alpha, and (1----4)-alpha-linked D-glucosyl disaccharides, respectively. Twenty-four combinations of starting conformations of the rotatable side-groups were considered for each disaccharide. Optimized structures were calculated using MM3 on a 20 degree grid spacing of the torsional angles about the glycosidic bonds. The energy surfaces of the six disaccharides were similar in many respects but differed in detail within the low-energy regions. The maps also illustrate the importance of the exo-anomeric effect and linkage type in determining the conformational flexibility of disaccharides. Torsional conformations of known crystal structures of maltosyl-containing molecules lie in a lower MM3 energy range than previously reported.

Carbohydrate Conformation↗
PubMed1992

Effects of dietary fat on cholesterol movement between tissues in CBA/J and C57BR/cdJ mice.

Differences in dietary fats cause differences in cholesterol metabolism in mice. CBA/J mice are resistant to diet-induced hypercholesterolemia and atherosclerosis; they adjust hepatic hydroxymethyl-glutaryl-CoA reductase activity (HMGR) to maintain homeostasis; C57BR/cdJ mice are susceptible, but young animals are thought to maintain homeostasis by changing fecal excretion of sterols. Compartmental modelling of movement of [4-14C]cholesterol was used to analyze movement of cholesterol between serum and liver, heart, and carcass in mice fed 40 en% fat, polyunsaturated to saturated fatty acid ratio (P/S) = 0.24 (US74) or 30 en% fat, P/S = 1 (MOD). Dietary effects were quite pronounced, while strain effects were more subdued. The C57/cdJ animals appear to regulate the overall cholesterol balance by reducing synthesis, as do the CBA/J animals, even though synthesis is not reduced to the same degree as in the CBA/J animals. Both diet and strain influence the whole-animal turnover rate, with slower turnover occurring for C57BR/cdJ animals and animals fed the US74 diet.

Animals↗
PubMed1991

Effect of temperature on the myoglobin-facilitated transport of oxygen in skeletal muscle.

An analysis of thermal effects on the facilitative transport of oxygen in skeletal muscle fibers is presented. Steady-state mass and energy transport balances are written and solved analytically or numerically using a finite-difference procedure. It is shown that no significant spatial thermal gradients exist due to internal reactions or bulk conduction effects across a muscle fiber. At typical muscle conditions, it is predicted that increased global temperature reduces the fraction of oxygenated myoglobin, increases local oxygen concentrations, and increases the percentage of oxygen flux attributed to oxy-myoglobin. The maximum supportable oxygen consumption rate, mO2max, is defined as the highest consumption rate sustainable without developing anoxic regions at the center of the fiber. By considering only temperature sensitive effects within fibers, mO2max is found to increase slightly with temperature at low temperatures. This increase is due to thermal effects on the diffusion coefficients as opposed to effects associated with the kinetics of the myoglobin-oxygen reaction. If the simulations include the temperature effect associated with oxygen solubility in blood plasma, mO2max decreases with temperature. A sensitivity analysis was performed by varying the values of relevant parameters. The maximum consumption rate was least affected by parameters associated with the kinetic and equilibrium constants and most affected by the diffusion coefficients and the concentration of myoglobin.

Animals↗
PubMed1986

Ventricular coupling in constrictive pericarditis.

Because of the close anatomic association, the volume or pressure in one ventricle can directly influence the volume and pressure in the other ventricle. Disease states that reduce pericardial compliance should accentuate this coupling between the ventricles. We examined this hypothesis in six dogs. Constrictive pericarditis was induced by injecting an irritant mixture into the pericardial cavity. Three to 4 weeks after this injection, the hearts were removed and placed in cool cardioplegic solution. Balloons were inserted into each ventricle and the pressure and volume changes caused by increasing the contralateral ventricular volume were measured. Compared with that in a control group of four dogs, the coupling between the ventricles was significantly augmented in the group with constrictive pericarditis. All the measured changes in ventricular pressure or volume caused by increasing contralateral ventricular pressure or volume were significantly greater (p less than .05) in the group with constrictive pericarditis. The results of these experiments show increased coupling between the ventricles with constrictive pericarditis, which helps to explain some of the signs and symptoms of constrictive pericarditis.

Animals↗