Biomedical subjects

J R Macdonald

Publications and source records attributed to J R Macdonald.

10 recordsLinked to original sources

PubMed2005

Analysis of conducting-system frequency response data for an interfacial amorphous phase of copper-core oxide-shell nanocomposites.

Complex electrical-conductivity experimental data sets for the interfacial amorphous phase in copper-core-copper-oxide-shell nanostructured composites have been analyzed using two Kohlrausch-related frequency response models recently developed for analysis of the dispersive electrical response of conductive materials. Such analysis has been carried out for both the precursor (herein referred to as the reference) glass as well as the glass in which the core-shell nanostructure was developed after suitable heat treatment. Complex nonlinear-least-squares data fitting at each temperature employed composite Kohlrausch models that included electrode effects. Because of the lack of sufficient high-frequency data, it was necessary to use fixed, rather than free, values of the shape parameter beta1 of the model. On the basis of topological considerations, its values were set at 13 and 23 for the reference glass and the core-shell structured glass, respectively. The activation energies of resistivity for the reference and the treated glasses were found to have values of about 2 and 0.4 eV, respectively, indicating two different mechanisms of electrical conduction. A blocking-electrode measurement on the reference glass indicated the presence of an electronic as well as an ionic component of the electrical conductivity, with the ionic part dominating at the temperatures for which the present analyses were carried out.

Journal Article↗

PubMed2005

Topological derivation of shape exponents for stretched exponential relaxation.

In homogeneous (ideal) glasses, the important dimensionless stretched-exponential shape parameter beta is described by magic (not adjusted) simple fractions derived from fractal configuration spaces of effective dimension d* determined by different topological axioms (rules) in the presence (absence) of a forcing electric field. The rules are based on a new central principle for defining glassy states: equal a priori distributions of fractal residual configurational entropy. Our approach and its beta estimates are fully supported by the results of relaxation measurements involving many different glassy materials and probe methods. The present unique topological predictions for beta typically agree with observed values to approximately 1% and indicate that for field-forced conditions beta should be constant for appreciable ranges of such exogenous variables as temperature and ionic concentration, as indeed observed using appropriate frequency-domain data analysis. The present approach can also be inverted and used to test sample homogeneity and quality.

Journal Article↗

PubMed2001

HSP47 binds cooperatively to triple helical type I collagen but has little effect on the thermal stability or rate of refolding.

HSP47, a collagen-specific molecular chaperone, interacts with unfolded and folded procollagens. Binding of chicken HSP47 to native bovine type I collagen was studied by fluorescence quenching and cooperative binding with a collagen concentration at half saturation (K(half)) of 1.4 x 10(-7) m, and a Hill coefficient of 4.3 was observed. Similar results are observed for the binding of mouse HSP47 recombinantly expressed in Escherichia coli. Chicken HSP47 binds equally well to native type II and type III procollagen without the carboxyl-terminal propeptide (pN type III collagen), but binding to triple helical collagen-like peptides is much weaker. Weak binding occurred to both hydroxylated and nonhydroxylated collagen-like peptides, and a significant chain length dependence was observed. Binding of HSP47 to native type I collagen had no effect on the thermal stability of the triple helix. Refolding of type I collagen in the presence of HSP47 showed minor changes, but these are probably not biologically significant. Binding of HSP47 to bovine pN type III collagen has only minor effects on the thermal stability of the triple helix and does not influence the refolding kinetics of the triple helix.

Animals↗

PubMed2001

Environmental features are important in determining protein secondary structure.

We have investigated amino acid features that determine secondary structure: (1) the solvent accessibility of each side chain, and (2) the interaction of each side chain with others one to four residues apart. Solvent accessibility is a simple model that distinguishes residue environment. The pairwise interactions represent a simple model of local side chain to side chain interactions. To test the importance of these features we developed an algorithm to separate alpha-helices, beta-strands, and "other" structure. Single residue and pairwise probabilities were determined for 25,141 samples from proteins with <30% homology. Combining the features of solvent accessibility with pairwise probabilities allows us to distinguish the three structures after cross validation at the 82.0% level. We gain 1.4% to 2.0% accuracy by optimizing the propensities, demonstrating that probabilities do not necessarily reflect propensities. Optimization of residue exposures, weights of all probabilities, and propensities increased accuracy to 84.0%.

Algorithms↗

PubMed1997

Postexercise protein-carbohydrate and carbohydrate supplements increase muscle glycogen in men and women.

We have previously demonstrated that women did not increase intramuscular glycogen in response to an increased percent of dietary carbohydrate (CHO) (from 60 to 75% of energy intake) (M. A. Tarnopolsky, S. A. Atkinson, S. M. Phillips, and J. D. MacDougall. J. Appl. Physiol. 78: 1360-1368, 1995). CHO and CHO-protein (Pro) supplementation postexercise can potentiate glycogen resynthesis compared with placebo (K. M. Zawadzki, B. B. Yaspelkis, and J. L. Ivy. J. Appl. Physiol. 72: 1854-1859, 1992). We studied the effect of isoenergetic CHO and CHO-Pro-Fat supplements on muscle glycogen resynthesis in the first 4 h after endurance exercise (90 min at 65% peak O2 consumption) in trained endurance athletes (men, n = 8; women, tested in midfollicular phase, n = 8). Each subject completed three sequential trials separated by 3 wk; a supplement was provided immediately and 1-h postexercise: 1) CHO (0.75 g/kg) + Pro (0.1 g/kg) + Fat (0.02 g/kg), 2) CHO (1 g/kg), and 3) placebo (Pl; artificial sweetener). Subjects were given prepackaged, isoenergetic, isonitrogenous diets, individualized to their habitual diet, for the day before and during the exercise trial. During exercise, women oxidized more lipid than did men (P < 0.05). Both of the supplement trials resulted in greater postexercise glucose and insulin compared with Pl (P < 0.01), with no gender differences. Similarly, both of these trials resulted in increased glycogen resynthesis (37.2 vs. 24. 6 mmol . kg dry muscle-1 . h-1, CHO vs. CHO-Pro-Fat, respectively) compared with Pl (7.5 mmol . kg dry muscle-1 . h-1; P < 0.001) with no gender differences. We conclude that postexercise CHO and CHO-Pro-Fat nutritional supplements can increase glycogen resynthesis to a greater extent than Pl for both men and women.

Adult↗

PubMed1993

Discrete and integral fourier transforms: analytical examples.

Analytical examples of the discrete Fourier transform (DFT) help in understanding relations between the DFT and the Fourier integral transform (FIT). Such examples enable one to estimate the errors involved when one transform is approximated by the other, and they suggest how such approximation errors might be reduced. We present mathematical and numerical analyses of the time-to-frequency DFT of the complex exponential function and of the frequency-to-time inverse DFT of the relaxation function. The FITs of these functions are exact inverses, and so they serve to clarify the effects of aliasing and truncation on the DFT.

Journal Article↗

PubMed1993

Structural analysis of the purine repressor, an Escherichia coli DNA-binding protein.

The purine repressor protein, PurR, is a member of the lac repressor, LacI, family of Escherichia coli DNA-binding proteins that bind DNA via a highly conserved N-terminal helix-turn-helix motif. Additionally, the members of this family display strong sequence homologies between their larger C-terminal effector binding/oligomerization domains. Analysis of the PurR primary and secondary structures reveals that its C-terminal corepressor binding domain is highly homologous to another group of E. coli-binding proteins, the periplasmic binding proteins, particularly to the ribose-binding protein (RBP). The high resolution x-ray structure of RBP allows this protein to serve as a template with which to model the predicted secondary structure of the corepressor binding domain of PurR. Similarly, the N-terminal DNA binding domain of PurR can be modeled using the NMR-determined structure of the corresponding region (residues 1-56) from LacI as a template. Combining the two, results in a description of the likely secondary structure topology of PurR and implicates residues important for corepressor binding and dimerization. CD spectroscopic studies on PurR, its corepressor binding domain and RBP result in secondary structure estimates nearly identical with those obtained by sequence analyses, thereby providing further corroborating physical evidence for this topological assignment.

Amino Acid Sequence↗

PubMed1992

Structural and functional characterization of Escherichia coli peptidyl-prolyl cis-trans isomerases.

Peptidyl-prolyl cis-trans isomerases (PPIases), enzymes that catalyze the cis-trans isomerization of peptide bonds to which proline contributes the nitrogen, were purified from Escherichia coli. In this organism, at least two PPIases are present. Both the cationic (periplasmic) and anionic (cytoplasmic) PPIases are inhibited by cyclosporin A with a Ki of 25-50 microM, a concentration 1000-fold higher than that required for eukaryotic PPIases. Although isoelectric focusing indicates that the two enzymes differ in isoelectric point by at least 4.0 pH units, the specific activities of the enzymes toward the tetrapeptide substrate succinyl-Ala-Ala-Pro-Phe-methyl-coumarylamide are equivalent. The activity of both enzymes for a series of substituted succinyl-Ala-Xaa-Pro-Phe-para-nitroanilide tetrapeptides suggests that the structure and function of the active site of the prokaryotic proteins is similar to that of eukaryotic cyclophilins. Both enzymes are capable of catalyzing the refolding of thermally denatured type III collagen. Antibodies against the periplasmic PPIase do not recognize the cytoplasmic enzyme, indicating significant differences in epitopes between the two forms. Circular dichroism spectroscopy indicates that the secondary structure of the cationic protein consists of 17% alpha-helix, 34% beta-sheet, 17% turns, 33% random coil and is very similar to human cytosolic PPIase.

Amino Acid Isomerases↗

PubMed1992

Impedance spectroscopy.

Impedance spectroscopy (IS) is a general term that subsumes the small-signal measurement of the linear electrical response of a material of interest (including electrode effects) and the subsequent analysis of the response to yield useful information about the physicochemical properties of the system. Analysis is generally carried out in the frequency domain, although measurements are sometimes made in the time domain and then Fourier transformed to the frequency domain. IS is by no means limited to the measurement and analysis of data at the impedance level (e.g., impedance vs. frequency) but may involve any of the four basic immittance levels: thus, most generally, IS stands for immittance spectroscopy.

Data Interpretation, Statistical↗

PubMedDate not supplied

Antitumor activity of irofulven against human ovarian cancer cell lines, human tumor colony-forming units, and xenografts.

The objective of this study was to investigate the cytotoxic activity of irofulven (HMAF, MGI 114), a unique chemotherapeutic agent currently under clinical investigation, in various preclinical models of ovarian cancer. Antiproliferative effects of irofulven in ovarian cancer cell lines and ovarian tumor specimens were characterized in vitro using sulforhodamine B and human tumor colony-forming assays, respectively. Irofulven demonstrated marked activity against a panel of ovarian tumor cell lines, including IGROV1, OVCAR-3, OVCAR-4, OVCAR-5, OVCAR-8, and SK-OV-3, all of which exhibit various drug resistance mechanisms. In human tumor cloning assays, irofulven inhibited colony formation in surgically derived ovarian tumors at concentrations as low as 0.001 micro g /ml and indicated superior activity in comparison with paclitaxel when tested against the same tumor specimens. The antitumor activity of irofulven compared to that of paclitaxel was also examined using the SK-OV-3 xenograft model. In mice bearing subcutaneously implanted SK-OV-3 tumors, treatment with paclitaxel failed to inhibit tumor growth; whereas mice treated with maximum tolerated doses of irofulven had a 25% partial shrinkage rate, and the remaining animals had a mean tumor growth inhibition of 82%. The potent activity of irofulven against ovarian tumors in vitro and in vivo supports the evaluation of its clinical activity in ovarian cancer.

Animals↗