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D Myers

Publications and source records attributed to D Myers.

14 recordsLinked to original sources
PubMed1992

Molecular code for cooperativity in hemoglobin.

Although tetrameric hemoglobin has been studied extensively as a prototype for understanding mechanisms of allosteric regulation, the functional and structural properties of its eight intermediate ligation forms have remained elusive. Recent experiments on the energetics of cooperativity of these intermediates, along with assignments of their quaternary structures, have revealed that the allosteric mechanism is controlled by a previously unrecognized symmetry feature: quaternary switching from form T to form R occurs whenever heme-site binding creates a tetramer with at least one ligated subunit on each dimeric half-molecule. This "symmetry rule" translates the configurational isomers of heme-site ligation into six observed switchpoints of quaternary transition. Cooperativity arises from both "concerted" quaternary switching and "sequential" modulation of binding within each quaternary form, T and R. Binding affinity is regulated through a hierarchical code of tertiary-quaternary coupling that includes the classical allosteric models as limiting cases.

Allosteric Regulation↗
PubMed1992

Beta/A4 deposits and their relationship to senile plaques in Alzheimer's disease.

The density and spatial pattern of immunostained beta/A4 deposits and mature senile plaques (SP) stained by the Glees method were compared in Alzheimer's diseased brain. Thirty-seven percent of the variance in Glees SP density in a tissue could be explained by beta/A4. Both lesions were clustered with the beta/A4 clusters often larger than the Glees SP clusters. Beta/A4 and Glees SP cluster size were not correlated in a tissue. The size of Glees SP clusters was positively correlated with SP density but no correlation could be detected for beta/A4. Hence, the density and spatial pattern of beta/A4 deposits in most tissues did not predict the development of Glees SP.

Alzheimer Disease↗
PubMed1991

Alzheimer's disease: size class frequency distribution of senile plaques: do they indicate when a brain tissue was affected?

The size class frequency distribution of a sample of senile plaques (SP) was determined in a total of 20 brain regions from 5 elderly cases of Alzheimer's disease (AD). The purpose of the study was to determine whether a comparison of the frequency distributions could be used to determine the chronology of SP development in the AD brain. SP from 10 microns to a maximum diameter of 160 microns were present in the tissue and the size class frequency distributions were positively skewed. The frequency distributions varied between brain regions in: (1) the size class containing the mode, (2) the degree of positive skew, and (3) the ratio of large to small SP. In most patients the ratio of large to small SP was higher in the hippocampus or adjacent gyrus compared with temporal, parietal and frontal neocortex. If the diameter of a SP reflects its age in the tissue than the data suggest that SP formed earlier either in the hippocampus or adjacent gyrus compared with the other neocortical tissues. However, this conclusion rests on a number of assumptions including: (1) that SP diameter is directly related to age, (2) that SP development occurs at similar rates in different brain regions and (3) that, once formed, SP are not removed from the tissue by astrocytes.

Alzheimer Disease↗
PubMed1991

Alzheimer's disease: the relationship between the density of senile plaques, neurofibrillary tangles and A4 protein in human patients.

The numerical density of senile plaques (SP) and neurofibrillary tangles (NFT) as revealed by the Glees silver method was compared with SP and NFT revealed by the Gallyas method and with amyloid (A4) deposits in immunostained sections in 6 elderly cases of Alzheimer's disease. The density of NFT was generally greater and A4 lower in tissue from hippocampus compared with the neocortex suggesting that A4 deposition was less important than the degree of paired helical filament (PHF) related damage in the hippocampus. The density of Glees SP was positively correlated Gallyas SP weakly correlated with A4 deposit number. A stepwise multiple regression analysis which included A4 deposit and Gallyas SP density and accounted for 54% of the variation in Glees SP density. Hence, different populations of SP were revealed by the different staining methods. The results suggested that the Glees method may stain a population of SP in a region of cortex where both amyloid deposition and neurofibrillary changes have occurred.

Alzheimer Disease↗
PubMed1990

Comparative least-squares analysis of hemoglobin oxygen equilibrium curves.

The oxygen-binding properties of hemoglobin have been studied at 600 microM protein concentration with organic phosphate, and analyzed by a series of different nonlinear least-squares analysis methods to determine whether reports of negligibly small values of the third overall Adair parameter, A3, are consequences of the data or a product of the data analysis. Data from other laboratories were analyzed as well. The single most important factor in creating a measurement that yields a small A3 is the use of equally weighted fitting in the Adair equation, while end-weighted fitting generally yields a larger A3. Endpoint extrapolation is ruled out as a major cause of abnormal A3 values. Monte Carlo simulations of the 600 microM results suggest that, if a small A3 were present, end weighting is at least as sensitive to a small A3 as equal weighting. We conclude that equally weighted fitting of the tetrameric Adair equation is unable to resolve the upper asymptote of the oxygen-binding data, resulting in an unusually small value for A3.

Hemoglobin A↗
PubMed1989

Blood-brain barrier to pertechnetate following drug-induced hypotension.

The integrity of the blood-brain barrier (BBB) was examined in rabbits, in terms of the partition of 99mTc-pertechnetate (99mTcO4-) between brain and blood, following intracarotid injection of hypertonic arabinose, hypertension (168 mm Hg and 10% inspired carbon dioxide), or hypotension (less than 20 mm Hg for 15 min). Corrections were made for changes in tissue blood contents, using chromium-51 as a red cell marker. In control animals the mean brain:blood ratio was 0.038 (range 0.027-0.052). Following arabinose there was a five-fold increase in mean BBB permeability (mean brain:blood ratio 0.192 (0.070-0.378)). There was no change after hypertension and carbon dioxide (mean ratio 0.034) or after hypotension (mean ratio 0.032), despite an increase in cerebral extracellular potassium. Examination of other tissues showed no change in the 99mTcO4- tissue/blood partition in heart muscle in any study but, following hypotension, ratios in the kidney (mean ratio 1.63) and, to a lesser extent, the liver (mean ratio 1.37) had increased, suggesting an abnormality of active transport under these conditions. We conclude that, while 99mTcO4- tissue/blood partitioning revealed osmotic disruption of the BBB, profound hypotension with evidence of brain cell damage did not change BBB permeability to the same marker. Hypotension may influence active transport of this ion in liver and kidney.

Animals↗
PubMed1988

The kinetic mechanism(s) of cytochrome oxidase. Techniques for their analysis and criteria for their validation.

The steady-state kinetics of cytochrome oxidase exhibit two characteristics that impose severe constraints on any proposed mechanism. The first is the exponential consumption of ferrocytochrome c and the second is the nonhyperbolic dependence of reaction velocity upon the concentration of cytochrome c. Because the reaction mechanism contains at least five, and possibly six, substrates, realistic mechanisms can be very complex and not suitable for analysis by conventional means. We have developed procedures for rapidly establishing whether a postulated mechanism will exhibit the necessary behavior and for calculating the steady-state activity that will result for any mechanism, given values for the individual rate constants and reactant concentrations. The procedures have been used with mechanisms containing up to 40 enzyme species.

Electron Transport Complex IV↗
PubMed1985

Magnetic circular dichroism studies on the heme and tryptophan components of cytochrome c peroxidase.

We have measured the magnetic circular dichroism of cytochrome c peroxidase and some of its derivatives from 250-350 nm. Comparison of the changes observed on conversion to the catalytic intermediate (cytochrome c peroxidase-I) with spectra obtained from horseradish peroxidase and its derivatives and model compounds of protoheme leads us to the conclusion that the observed changes in the magnetic circular dichroism spectra reflect conversion of the heme to the ferryl state. No evidence was found for modification of tryptophan in cytochrome c peroxidase-I.

Cyanides↗
PubMed1978

Impediments to the course and effectiveness of discharge planning.

This paper examines the proposition that "timing" (of referral) is a crucial element in determining the effectiveness of the discharge planning process. A brief review of the relevant literature is followed by the description of a study undertaken to assess the impact that various impediments had upon discharge planning practice in two matched ward populations of a large, acute care university hospital. Along with timing, three other impediments were identified and their influence assessed; (a) noncompletion of transfer forms required; (b) unavailability of an appropriate (i.e., needed level of care) bed in an approved facility; and(c) unanticipated change in the patient's medical condition. Some implications of the findings are examined and discussed, and directions for future study are identified. Appended are facsimiles of the instruments employed.

Hospital Departments↗
PubMedDate not supplied

Platypus envenomation--a painful learning experience.

OBJECTIVE: To describe in detail for the first time, the clinical course and medical management of a significant human envenomation by the Australian platypus (Ornithorhynchus anatinus). CLINICAL FEATURES: A 57-year-old man was envenomated via two spur wounds to the right hand from each hind leg of a male platypus. Pain was immediate, sustained, and devastating; traditional first aid analgesic methods were ineffective. INTERVENTION AND OUTCOME: On admission to hospital, narcotics administered intravenously, both intermittently and by infusion, provided inadequate analgesia. A right wrist block was dramatically effective. After the blockade narcotic analgesic support was required for several days. The patient spent six days in hospital, and the envenomated area remained painful, swollen and with little movement for three weeks. Significant functional impairment of the hand persisted for three months, the cause of which is uncertain. CONCLUSIONS: Male platypus venom remains largely unstudied. It produces savage local pain and marked local swelling, but no apparent tissue ischaemia. No antivenom is available; in its absence the only effective analgesia appears to be regional nerve blockade, when the envenomation site and available skills permit. Immobilisation assists.

Animals↗