Biomedical subjects
C R Meyer
Publications and source records attributed to C R Meyer.
When medicine can't cure.
Explore the source record for details and available documents.
Easing the growing pains.
Explore the source record for details and available documents.
Division of labor.
Explore the source record for details and available documents.
Enough to raise one's blood pressure.
Explore the source record for details and available documents.
Applying the healing arts to health system reform.
Explore the source record for details and available documents.
The computerized medical record in action.
Before the advent of the IPS computerized medical record at Burlington, Zallen did not own a computer. Although he learned touch-typing in high school, he emphatically states that he hated it. The average age of the physicians on staff at Burlington is about 40, but few had extensive previous experience with computers. According to Zallen, all have adapted to the CPR with few tears or tirades. The physicians continue to "tweak" the system to customize their own scrapbook and templates. Lahey physicians who work at Burlington part time are using the system, although with more staff help. The CPR is alive and well at Burlington Health Center. HCHP physicians can and do use computers in their daily work, producing quality medical records that are readable and retrievable. Nonetheless, promises that computers will make records more complete and accessible and will improve quality measurement will be mere blather if the CPR doesn't make users' lives easier. My last question to Zallen was "How has this system made your life harder?" After one pensive second, he replied, "I really can't think of anything." To me, that is potent testimony that the CPR is not a techie's fantasy, but rather, a pragmatic, workable answer to the needs of 21st century medicine.
Quantitative assessment of cartilage surface roughness in osteoarthritis using high frequency ultrasound.
Osteoarthritis (OA) is a common disease which affects nearly 50% of people over age 60. Histologic evaluation suggests that fibrillations approximately 20-150 microns are among the earliest changes in the articular cartilage. We propose a technique to quantify these surface fibrillatory changes in osteoarthritic articular cartilage by considering the angular distribution of the envelope-detected backscattered pressure field from an incident 30-MHz focused transducer. The angular distribution of the scattered acoustic field from an inosonifying source will directly relate to the distribution of surface fibrillatory changes. Data are presented for three different grades (400, 500 and 600 grit) of commercially available emory paper and three samples of osteoarthritic femoral head articular cartilage, which were visually assessed as having smooth, intermediate and rough surfaces, respectively. Our preliminary results indicate a probable monotonic relationship between articular cartilage roughening and the degree of broadening in the angle-dependent pressure amplitude. When applied to the emory paper, the technique indicates sensitivity to differences as small as approximately 5-10 microns in mean roughness. This procedure may provide an extremely sensitive and reproducible means of quantifying and following the cartilage changes observed in early osteoarthritis.
Cloning, expression, and nucleotide sequence of a mutant glgC gene from Escherichia coli B.
A mutant glgC gene contained in a 10.9-kb PstI fragment was cloned from the Escherichia coli B strain SG5 via colony hybridization by using a wild-type glgC probe. The altered allosteric properties of the expressed ADPglucose synthetase were found to result from the conversion of proline to serine at amino acid residue 295.
Media mishandle medical news.
Explore the source record for details and available documents.
Regulation of Phosphoenolpyruvate carboxylase from Crassula argentea: effect of incubation with ligands and dilution on oligomeric state, activity, and allosteric properties.
The relationship between the aggregation state and allosteric properties of purified phosphoenolpyruvate carboxylase from Crassula argentea was examined using both kinetic and physical techniques. Analysis by native polyacrylamide gel electrophoresis showed that dilution induced a dissociation of the active tetramer to a less active dimer. Kinetic assays showed that inhibition of phosphoenolpyruvate carboxylase by 5 mM malate measured at a saturating phosphoenolpyruvate concentration rose to nearly 80% with increasing preassay dilution while the activity in the absence of malate remained constant. Kinetic bursts were observed when enzyme-initiated assays were measured at a subsaturating phosphoenolpyruvate concentration. At saturating phosphoenolpyruvate concentrations, however, increasing lags developed in response to increasing the preassay dilution of the enzyme. Further, dynamic laser-light scattering measurements showed that preincubation of the dilute enzyme with phosphoenolpyruvate stabilized the tetramer while the presence of malate induced dimer formation. These observations confirm and extend earlier work with the extracted active malate insensitive night and less active, malate-sensitive day forms of the enzyme (Wu and Wedding [1985] Plant Physiol. 77, 667-675). Activity measured at subsaturating phosphoenolpyruvate concentrations dropped with increasing preassay dilution of enzyme, while activation by 3.2 mM glucose 6-phosphate, assayed at a low phosphoenolpyruvate concentration (0.044 mM), increased with dilution to nearly 400%. In this case activation results from a decrease in the control rate as the activity measured in the presence of glucose 6-phosphate was nearly constant, similar in effect to saturating phosphoenolpyruvate in the assay. Glucose 6-phosphate induced tetramer formation of the dilute enzyme as measured by light-scattering similar to the effects induced by PEP. In addition, when diluted (dimeric) PEPC was preincubated with PEP or glucose 6-phosphate the enzyme became less sensitive to malate inhibition, while the active-site directed ligand 2-phosphoglycolate had no effect on malate inhibition. These results indicate that both the substrate PEP and the activator glucose 6-phosphate stabilize the active tetramer via binding and interaction at an activator site separate from the active site.
Pre- to postnatal reduction in ultrasound attenuation coefficient of the liver.
A recent study showed the ultrasound attenuation coefficient of fetal liver between 26 and 40 weeks of gestation to be 26% higher than after birth. To test the hypothesis that ultrasound attenuation is sensitive to fetal liver glycogen concentration, the livers of 24 fetuses were examined at 5 MHz just prior to and just after birth. The mean pre- to post-delivery reduction in attenuation coefficient was 0.08 dB cm-1 MHz-1 +/- 0.02 (SEM), or 17% of the post-delivery mean. This is consistent with the increase in attenuation measured by others in liver homogenate when glycogen was added. An increase in measurement accuracy, correlation with glycogen content, and, possibly, control for biological variability will be required to make predictions in individual cases, as opposed to these averages. A simple test of glycogen content would be of value scientifically and in prenatal and postnatal management.
Intravascular ultrasound imaging of vascular responsiveness in isolated perfused canine arteries.
We investigated the feasibility of using intravascular ultrasound imaging to analyze vascular physiology in various arterial beds. Canine superficial femoral, external iliac, and common carotid arteries were harvested and suspended and perfused in a bath of oxygenated, heated, physiologic salt solution. A 6-Fr, 20-MHz ultrasound imaging catheter was inserted into the lumen of the arteries and serial images were acquired after bolus injections of either serotonin or normal saline into the extravascular bathing medium. Serotonin resulted in a significant time- and dose-dependent decrease in cross-sectional area in muscular femoral arteries (P less than .001): -5.2% with 10(-8) M serotonin, -15% with 10(-7) M, and -28% with 10(-6) M. Histologically transitional iliac arteries demonstrated less marked changes, while elastic carotid arteries demonstrated no significant changes. Our results indicate that intravascular ultrasound may be used to quantify and differentiate responses to vasoconstrictive agents in different vascular beds.
The influence of pH on substrate form specificity of phosphoenolpyruvate carboxylase purified from Crassula argentea.
Purified phosphoenolpyruvate carboxylase from both the crassulacean acid metabolism plant Crassula argentea and the C4 plant Zea mays was shown by kinetic studies at saturating fixed-varying concentrations of free mg2+ to selectively use the metal-complexed form of phosphoenolpyruvate when assayed at pH 8.0. A similar response to added magnesium at high free phosphoenolpyruvate concentrations was obtained for both enzymes, consistent with the use of the complex as the substrate. Kinetic studies at pH 7.0 indicated that at this pH the total concentration of phosphoenolpyruvate (including both free and metal-complexed forms) could be used by the enzyme from C.argentea while the C4 enzyme still utilized the complex. The loss of specificity induced by the decrease in the pH of the assay medium was accompanied by a decrease in the Km of this enzyme for phosphoenolpyruvate whatever the form considered and an increase in Vmax/Km. In contrast, a similar decrease of pH led to an increased Km of the C4 enzyme for phosphoenolpyruvate and a decrease of Vmax/Km. For the enzyme from C. argentea (previously shown to contain an essential arginine at the active site), protection of activity by the different forms of substrate against inactivation by the specific arginyl reagent 2,3-butanedione changes markedly with pH. At pH 8.1, the metal complex is the better protector while at pH 7.0 free phosphoenolpyruvate gives the best protection consistent with the observed kinetic changes in substrate form utilization. The relationship between the enzyme affinity for substrate, substrate specificity, and the requirement for magnesium for substrate turnover is discussed.
The role of oligomerization in regulation of maize phosphoenolpyruvate carboxylase activity. Influence of Mg-PEP and malate on the oligomeric equilibrium of PEP carboxylase.
A purification procedure which yields a near homogenous preparation of phosphoenolpyruvate (PEP) carboxylase from the leaves of Zea mays is reported. The enzyme had a final specific activity of 33.3 micromoles per minute per milligram protein. Size exclusion high performance liquid chromatography and dynamic laser-light scattering spectroscopy showed that PEP carboxylase exists in an equilibrium of aggregates. Enzyme predominantly in the dimeric configuration is less active (when assayed at sub-optimal Mg-PEP concentrations, less than 0.4 millimolar) than when in its tetrameric arrangement. The difference in activity diminishes and disappears as the concentration of the substrate Mg-PEP increases. The substrate drives the equilibrium toward the tetramer, while malate, an inhibitor of PEP carboxylase, shifts the equilibrium toward the dimer. It thus appears that the quaternary structure (oligomeric state) of maize PEP carboxylase can be regulated by the naturally occurring effector molecules Mg-PEP and malate which in turn can control the enzyme's activity.
Regulation of the aggregation state of maize phosphoenolpyruvate carboxylase: evidence from dynamic light-scattering measurements.
The molecular weights of different aggregational states of phosphoenolpyruvate carboxylase purified from the leaves of Zea mays have been determined by measurement of the molecular diameter using a Malvern dynamic light scattering spectrometer. Using these data to identify the monomer, dimer, tetramer, and larger aggregate(s) the effect of pH and various ligands on the aggregational equilibria of this enzyme have been determined. At neutral pH the enzyme favored the tetrameric form. At both low and high pH the tetramer dissociated, followed by aggregation to a "large" inactive form. The order of dissociation at least at low pH appeared to be two-step: from tetramer to dimers followed by dimer to monomers. The monomers then aggregate to a large aggregate, which is inactive. The presence of EDTA at pH 8 protected the enzyme against both inactivation and large aggregate formation. Dilution of the enzyme at pH 7 at room temperature results in driving the equilibrium from tetramer to dimer. The presence of malate with EDTA stabilizes the dimer as the predominant form at low protein concentrations. The presence of the substrate phosphoenolpyruvate alone and with magnesium and bicarbonate induced formation of the tetramer, and decreased the dissociation constant (Kd) of the tetrameric form. The inhibitor malate, however, induced dissociation of the tetramer as evidenced by an increase in the Kd of the tetramer.