Ventricular pressure-volume curve indices change with end-diastolic pressure.
Many indices have been proposed to describee the diastolic pressure-volume curve mathematically and permit quantification of the elastic properties of the myocardium itself in hopes that changes in the muscle caused by disease would b.e reflected in the diastolic pressure-volume curve. To date, none of the proposed indices has been shown convincingly to discriminate one group of patients from another. While this situation in part arises from the relatively large amount of noise introduced by the technical difficulties of measuring synchronous pressures and volumes during diastole in man, ther is a more fundamental difficulty. In practice, one can measure only a short segment of the entire pressure-volume curve, and the values of all diastolic pressure-volume curve parameters investigated change significantly when one uses different segments of the same pressure-volume curve to compute them. These results were derived from relatively noise-free pressure-volume curves obtained by filling nine excised dog left ventricles at a known rate and monitoring pressure-volume curve used to compute the parameter. Merely increasing measurement fidelity will not resolve this problem, because none of these parameters accurately characterizes the entire diastolic pressure-volume curbe from a segment like that which one can reasonably expect to obtain from humans. (+info)
Evaluation of the force-frequency relationship as a descriptor of the inotropic state of canine left ventricular myocardium.
The short-term force-frequency characteristics of canine left ventricular myocardium were examined in both isolated and intact preparations by briefly pertubing the frequency of contraction with early extrasystoles. The maximum rate of rise of isometric tension (Fmas) of the isolated trabeculae carneae was potentiated by the introduction of extrasystoles. The ratio of Fmas of potentiated to control beats (force-frequency ratio) was not altered significantly by a change in muscle length. However, exposure of the trabeculae to isoproterenol (10(-7)M) significantly changed the force-frequency ratio obtained in response to a constant frequency perturbation. Similar experiments were performed on chronically instrumented conscious dogs. Left ventricular minor axis diameter was measured with implanted pulse-transit ultrasonic dimension transducers, and intracavitary pressure was measured with a high fidelity micromanometer. Atrial pacing was performed so that the end-diastolic diameters of the beats preceding and following the extrasystole could be made identical. Large increases in the maximum rate of rise of pressure (Pmas) were seen in the contraction after the extrasystole. The ratio of Pmax of the potentiated beat to that of the control beat was not changed by a 9% increase in the end-diastolic diameter, produced by saline infusion. Conversely, isoproterenol significantly altered this relationship in the same manner as in the isolated muscle. Thus, either in vitro or in situ, left ventricular myocardium exhibits large functional changes in response to brief perturbations in rate. The isoproterenol and length data indicate that the force-frequency ratio reflects frequency-dependent changes in the inotropic state, independent of changes in length. (+info)
Subunit dissociation in fish hemoglobins.
The tetramer-dimer dissociation equilibria (K 4,2) of several fish hemoglobins have been examined by sedimentation velocity measurements with a scanner-computer system for the ultracentrifuge and by flash photolysis measurements using rapid kinetic methods. Samples studied in detail included hemoglobins from a marine teleost, Brevoortia tyrannus (common name, menhaden); a fresh water teleost, Cyprinus carpio, (common name, carp); and an elasmobranch Prionace glauca (common name, blue shark). For all three species in the CO form at pH 7, in 0.1 M phosphate buffer, sedimentation coefficients of 4.3 S (typical of tetrameric hemoglobin) are observed in the micromolar concentration range. In contrast, mammalian hemoglobins dissociate appreciably to dimers under these conditions. The inability to detect dissociation in three fish hemoglobins at the lowest concentrations examined indicates that K 4,2 must have a value of 10(-8) M or less. In flash photolysis experiments on very dilute solutions in long path length cells, two kinetic components were detected with their proportions varying as expected for an equilibrium between tetramers (the slower component) and dimers (the faster component); values of K 4,2 for the three fish hemoglobins in the range 10(-9) to 10(-8) M were calculated from these data. Thus, the values of K 4,2 for liganded forms of the fish hemoglobins appear to be midway between the value for liganded human hemoglobin (K 4,2 approximately 10(-6) M) and unliganded human hemoglobin (K 4,2 approximately 10(-12) M). This conclusion is supported by measurements on solutions containing guanidine hydrochloride to enhance the degree of dissociation. All three fish hemoglobins are appreciably dissociated at guanidine concentrations of about 0.8 M, which is roughly midway between the guanidine concentrations needed to cause comparable dissociation of liganded human hemoglobin (about 0.4 M) and unliganded human hemoglobin (about 1.6 M). Kinetic measurements on solutions containing guanidine hydrochloride indicated that there are changes in both the absolute rates and the proportions of the fast and slow components, which along with other factors complicated the analysis of the data in terms of dissociation constants. Measurements were also made in solutions containing urea to promote dissociation, but with this agent very high concentrations (about 6 M) were required to give measureable dissociation and the fish hemoglobins were unstable under these conditions, with appreciable loss of absorbance spectra in both the sedimentation and kinetic experiments. (+info)
Using computerized video time lapse for quantifying cell death of X-irradiated rat embryo cells transfected with c-myc or c-Ha-ras.
Rat embryo fibroblasts that had been transfected with the c-myc or c-Ha-ras oncogene were X-irradiated, after which individual cells and their progeny were followed in multiple fields for 5-6 days by computerized video time lapse microscopy to quantify the lethal events that resulted in loss of clonogenic survival. The loss of clonogenic survival of X-irradiated (9.5 or 2.5 Gy) REC:myc cells was attributed almost entirely to the cells dying by apoptosis, with almost all of the apoptosis occurring after the progeny had divided from one to four times. In contrast, the loss of clonogenic survival of X-irradiated REC:ras cells was attributed to two processes. After 9.5 Gy, approximately approximately 60% of the nonclonogenic cells died by apoptosis (with a very small amount of necrosis), and the other 40% underwent a senescent-type process in which some of the cells and their progeny stopped dividing but remained as viable cells throughout 140 h of observation. Both processes usually occurred after the cells had divided and continued to occur in the cells' progeny for up to five divisions after irradiation. Furthermore, the duration of the apoptotic process was shorter for REC:myc cells (0.5-1 h) than for REC:ras cells (4-5 h). By using computerized video time lapse to follow individual cells, we were able to determine the mode of cell death. This cannot be determined by conventional clonogenic survival experiments. Also, only by following the individual cells and their progeny can the true amount of apoptosis be determined. The cumulative percentage of apoptosis scored in whole populations, without distinguishing between the progeny of individually irradiated cells, does not reflect the true amount of apoptosis that occurs in cells that undergo postmitotic apoptosis after irradiation. Scoring cell death in whole populations of cells gives erroneous results because both clonogenic and nonclonogenic cells are dividing as nonclonogenic cells are apoptosing or senescing over a period of many days. For example, after 9.5 Gy, which causes reproductive cell death in 99% of both types of cells, the cumulative percentage of the cells scored as dead in the whole population at 60- 80 h after irradiation, when the maximum amount of cumulative apoptosis occurred, was approximately 60% for REC:myc cells, compared with only approximately 40% for REC:ras cells. (+info)
Model studies of chromatin structure based on X-ray diffraction data.
Model calculations are presented in order to interpret the X-ray diffraction diagrams given by chromatin gels. It is shown that by taking into account the hydration of chromatin subunits, the problem of calculating the interference function in concentrated gels is greatly simplified. In this way it is spossible to fully interpret the influence of concentration on the position and intensity of the various rings present in the X-ray diffraction patterns. The possibilities and limitations of models based on spherical symmetry are also discussed. It is concluded that each chromatin subunit most likely contains three turns of DNA in each 200 base pairs segment surrounding a central protein core. With the method presented here it is possible to test if other models of chromatin based on different kinds of evidence are compatible with the X-ray diffraction data. (+info)
Automated collection of quality-of-life data: a comparison of paper and computer touch-screen questionnaires.
PURPOSE: To evaluate alternative automated methods of collecting data on quality of life (QOL) in cancer patients. After initial evaluation of a range of technologies, we compared computer touch-screen questionnaires with paper questionnaires scanned by optical reading systems in terms of patients' acceptance, data quality, and reliability. PATIENTS AND METHODS: In a randomized cross-over trial, 149 cancer patients completed the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-Core 30, version 2.0 (EORTC QLQ-C30), and the Hospital Anxiety and Depression Scale (HADS) on paper and on a touch screen. In a further test-retest study, 81 patients completed the electronic version of the questionnaires twice, with a time interval of 3 hours between questionnaires. RESULTS: Fifty-two percent of the patients preferred the touch screen to paper; 24% had no preference. The quality of the data collected with the touch-screen system was good, with no missed responses. At the group level, the differences between scores obtained with the two modes of administration of the instruments were small, suggesting equivalence for most of the QOL scales, with the possible exception of the emotional, fatigue, and nausea/vomiting scales and the appetite item, where patients tended to give more positive responses on the touch screen. At the individual patient level, the agreement was good, with a kappa coefficient from 0.57 to 0.77 and percent global agreement from 61% to 97%. The electronic questionnaire had good test-retest reliability, with correlation coefficients between the two administrations from 0.78 to 0.95, kappa coefficients of agreement from 0.55 to 0.90, and percent global agreement from 56% to 100%. CONCLUSION: Computer touch-screen QOL questionnaires were well accepted by cancer patients, with good data quality and reliability. (+info)
Binding conformers searching method for ligands according to the structures of their receptors and its application to thrombin inhibitors.
AIM: To develop a method of finding binding conformers for ligands according to the three-dimensional structures of their receptors. METHODS: Combining the systematic search method of ligand with the molecular docking approach of ligand fitting into its receptor, we developed a binding conformer searching method for ligands. RESULTS: The binding conformers of phosphonopeptidyl thrombin inhibitors were recognized. The binding (interaction) energies between these inhibitors and thrombin were calculated with molecular mechanical method. CONCLUSION: Both of the total binding energies and steric binding energies have good correlations with the inhibitory activities of these thrombin inhibitors, demonstrating that our approach is reasonable. It can also be used to explain the inhibition mechanism of thrombin interacting with these inhibitors. (+info)
Computer method for predicting the secondary structure of single-stranded RNA.
We present a computer method utilizing published values for base pairing energies to compute the most energetically favorable secondary structure of an RNA from its primary nucleotide sequence. After listing all possible double-helical regions, every pair of mutally incompatible regions (whose nucleotides overlap) is examined to determine whether parts of those two regions can be combined by branch migration to form a pair of compatible new subregions which together are more stable than either of the original regions separately. These subregions are added to the list of base pairing regions which will compete to form the best overall structure. Then, a 'hyperstructure matrix' is generated, containing the unique topological relationship between every pair of regions. We have shown that the best structure can be chosen directly from this matrix, without the necessity of creating and examing every possible secondary structure. We have included the results from our solution of the 5S rRNA of the cyanobacterium Anacystis nidulans as an example of our program's capabilities. (+info)