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Biomedical subjects

Z Hillel

Publications and source records attributed to Z Hillel.

14 recordsLinked to original sources
PubMed1990

Importance of atrial systole to ventricular filling predicted by transesophageal echocardiography.

This study documented mitral flow velocity patterns in anesthetized patients with ischemic heart disease and left ventricular dysfunction and investigated the relationship between transmitral flow velocity measurements and the hemodynamic response to ventricular pacing. Twenty-four patients in sinus rhythm without evidence of mitral valve disease undergoing elective myocardial revascularization were studied. Anesthesia consisted of a high-dose opioid-muscle relaxant-oxygen technique. After endotracheal intubation a 3.5-MHz phased-array transesophageal echocardiographic probe was inserted and positioned to obtain a long-axis view of the left atrium and left ventricle. The Doppler sample volume was placed at the mitral annulus with minimal cursor angulation, and the biphasic velocity tracing of transmitral blood flow was recorded. A hemodynamic profile was obtained, and cardiac output was measured in triplicate by thermodilution. Ventricular pacing was then instituted and the hemodynamic and thermodilution measurements were repeated. The peak early filling (E) velocity was 0.34 +/- 0.11 m/s, and the peak atrial (A) velocity was 0.38 +/- 0.09 m/s. The mean E:A ratio was 0.91 +/- 0.3, and the median value was 0.88. In sinus rhythm the cardiac index of those patients with an E:A greater than 0.88 (group 1) was 1.97 +/- 0.32 l/min and those with an E:A less than 0.88 (group 2) was 1.76 +/- 0.50 (NS). During ventricular pacing the patients in group 1 (1.56 +/- 0.32 l/min) had significantly higher cardiac indices than those in group 2 (1.21 +/- 0.31 l/min) (P less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1989

Effects of doxacurium chloride on biventricular cardiac function in patients with cardiac disease.

The effects of doxacurium chloride, a new long-acting non-depolarizing neuromuscular blocking drug, on cardiac performance were studied in 45 patients undergoing high-dose fentanyl-diazepam-oxygen anaesthesia for cardiac surgery. Data were collected at baseline (10 min after tracheal intubation), and at 2, 5 and 10 min after an i.v. bolus of doxacurium with a rapid-response thermistor pulmonary arterial catheter, using two-dimensional transoesophageal echocardiography, and direct arterial pressure measurement. The patients were allocated to four groups based on the type of surgery and dose of doxacurium (0.05 or 0.08 mg kg-1). No changes in left or right ventricular dimensions or contractility were detected in any group. Although significant changes (P less than 0.05) occurred in several groups, all these changes were clinically insignificant (less than 10% change from baseline values), and were similar to those seen in unstimulated anaesthetized patients. Doxacurium appears to be a safe drug for use in patients undergoing cardiac surgery, and is devoid of significant cardiovascular side effects in the doses tested.

Adolescent↗
PubMed1988

Left ventricular performance indices by transesophageal Doppler.

The purpose of this study was to assess whether blood flow velocity signals, obtained by esophageal continuous-wave Doppler, reflect changes in ventricular performance. Ventricular performance has previously been determined by analysis of blood flow velocity signals sampled in the ascending aorta. In this investigation velocity signals were acquired from the descending aorta, with the use of an esophageal Doppler transducer. Maximum blood flow velocity (Vm), maximum blood flow volume acceleration (Accv), and maximum linear blood flow acceleration (Acc) were the velocity signals used to evaluate left ventricular performance. Twenty-six patients scheduled for myocardial revascularization and anesthetized with fentanyl (50 micrograms/kg) and pancuronium (0.15 mg/kg) were studied. In seven patients (Group I) a good correlation (r = 0.91) was observed between Accv in the ascending and descending aorta. In 10 patients (Group 2), halothane (0.5 and 1.0 MAC end-tidal) was added to the anesthetic. At these halothane concentrations Vm, Accv, and Acc measured in the descending aorta remained unchanged. Decreases were noted in the product of mean arterial pressure (MAP) and Acc (P-Acc; decreased 20% at 0.5 MAC and 39% at 1 MAC) and the product of systemic vascular resistance and Acc (R-Acc; decreased 25% at 1 MAC). In nine patients (Group 3), phenylephrine was used to reverse the decrease in MAP induced by 1 MAC halothane. Under these conditions Vm, Accv, Acc, and P-Acc showed similar decreases (approximately 30% of baseline values), whereas R-Acc returned to baseline values. In summary, indices of blood flow in the descending aorta were easily determined with a commercial transesophageal continuous-wave Doppler device. Descending and ascending aortic blood flow Accv correlated well, and the changes in the product of MAP and Acc in the descending aorta reflected the anticipated, halothane-induced, changes in left ventricular performance. In conclusion, descending aortic blood flow acceleration contains information on left ventricular performance that can be derived by the minimally invasive transesophageal Doppler technique.

Aorta, Thoracic↗
PubMed1987

A comparison of hemodynamic indices derived by invasive monitoring and two-dimensional echocardiography.

Intraoperative two-dimensional echocardiography (2D-echo) is useful for monitoring global and regional left ventricular function. The 2D-echo view most frequently utilized during intraoperative monitoring is the short-axis view at the level of the papillary muscles. To determine whether hemodynamic data can be derived from this single 2D-echo short-axis view, 12 patients undergoing coronary artery bypass grafting (CABG) were studied. All patients had normal left-ventricular function preoperatively (ejection fraction = 64% +/- 12%). Echo-data were obtained before and after cardiopulmonary bypass (CPB) by epicardial placement of a 5 MHz echo-transducer. The correlation between thermodilution and echo-derived cardiac indices was good (r = 0.8), and not significantly different from the correlation between stroke indices (r = 0.68). A strong positive correlation was established between end-diastolic volume index and echo cardiac index (CIE) (r = 0.93 before CPB; r = 0.91 after CPB) and end-diastolic area index and CIE (r = 0.94 before CPB; r = 0.91 after CPB). The pulmonary capillary wedge pressure was not a determinant of cardiac index before or after cardiopulmonary bypass. No correlation was observed between systemic vascular resistance and echo-derived wall stress. These findings demonstrate that, in patients with good left-ventricular function undergoing CABG surgery, 2D-echo provides a better index of left-ventricular preload than conventional invasive hemodynamic monitoring.

Coronary Artery Bypass↗
PubMed1983

A rapid mixing-photocrosslinking technique to study the dynamics of nucleic acid-protein interactions.

A rapid mixing-photocrosslinking technique has been developed to investigate the kinetics of protein-nucleic acid interactions. With this technique, binding of nucleic acid to protein is first synchronized by rapid mixing in a stopped-flow apparatus. The intermediates formed at different stages of the binding process are then "frozen" by photocrosslinking with a 10-microseconds uv light pulse at various times after mixing. By analyzing structural changes of these intermediates as a function of time, one can obtain the information concerning the dynamic aspects of the interaction. This technique may also be applied to other macromolecular interactions in biological systems.

DNA↗
PubMed1978

Photochemical cross-linking studies on the interaction of Escherichia coli RNA polymerase with T7 DNA.

We have identified the subunits of Escherichia coli RNA polymerase which are in close contact with the T7 phage DNA template using photochemical cross-linking. In nonspecific T7 DNA-enzyme complexes which occur in all regions of the DNA, subunits sigma, beta, and beta' were cross-linked to the DNA. In contrast, in specific binary complexes which presumably occur at promoter sites, and in the initiation complex (holoenzyme + T7 DNA + initiator dinucleotides + three nucleoside triphosphates), only sigma and beta were cross-linked to DNA, while cross-linking of beta' could not be demonstrated. These results (1) do not support the idea that alpha subunits are involved in the enzyme-template interaction, (2) raise the possibility that sigma subunit participates directly in promoter recognition even though isolated sigma does not bind to DNA, and (3) indicate different modes of interaction between RNA polymerase and DNA in nonspecific and specific complexes. These findings are relevant to the mechanism by which RNA polymerase carries out selective transcription.

Coliphages↗
PubMed1977

Subunit topography of RNA polymerase from Escherichia coli. A cross-linking study with bifunctional reagents.

The quaternary structures of Escherichia coli DNA-dependent RNA polymerase holenzyme (alpha 2 beta beta' sigma) and core enzyme (alpha 2 beta beta') have been investigated by chemical cross-linking with a cleavable bifunctional reagent, methyl 4-mercaptobutyrimidate, and noncleavable reagents, dimethyl suberimidate and N,N'-(1,4-phenylene)bismaleimide. A model of the subunit organization deduced from cross-linked subunit neighbors identified by dodecyl sulfate-polyacrylamide gel electrophoresis indicates that the large beta and beta' subunits constitute the backbone of both core and holoenzyme, while sigma and two alpha subunits interact with this structure along the contact domain of beta and beta' subunits. In holoenzyme, sigma subunit is in the vicinity of at least one alpha subunit. The two alpha subunits are close to each other in holoenzyme, core enzyme, and the isolated alpha 2 beta complex. Cross-linking of the "premature" core and holoenzyme intermediates in the in vitro reconstitution of active enzyme from isolated subunits suggests that these species are composed of subunit complexes of molecular weight lower than that of native core and holoenzyme, respectively. The structural information obtained for RNA polymerase and its subcomplexes has important implications for the enzyme-promoter recognition as well as the mechanism of subunit assembly of the enzyme.

DNA-Directed RNA Polymerases↗
PubMed1976

Spatial relationship of the sigma subunit and the rifampicin binding site in RNA polymerase of Escherichia coli.

sigma subunit of Escherichia coli RNA polymerase is known to stimulate specific RNA chain initiation. Rifampicin, an inhibitor of RNA chain initiation, binds to a single site on the beta subunit of RNA polymerase. We have used the fluorescence energy transfer technique to deduce proximity relationships of sigma subunit and rifampicin binding site on the enzyme. Isolated sigma subunit was covalently labeled with fluorescent donors in two ways: specific labeling of a single sulfhydryl residue with N-(iodoacetylaminoethyl)-5-naphthylamine-1-sulfonate (1,5-I-AENS) and nonspecific labeling on the surface of the protein with dansyl chloride (Dns-Cl) adsorbed on Celite. The labeled sigma subunits were biologically active and formed a stoichiometric complex with core polymerase. The efficiency of energy transfer was obtained from the fluorescence intensity and the excited-state lifetime of the sigma-labeled holoenzyme in the presence and absence of rifampicin, which served as an energy acceptor. The transfer efficiency (2%) from AENS to rifampicin placed AENS somewhere between 42 and 85 A away from the rifampicin binding site. The rotational mobility of the donor was determined by nanosecond fluorescence depolarization spectroscopy, while the acceptor orientation was assumed to be fixed at some unknown angle. The efficiency measured for energy transfer from Dns to rifampicin was 10% in the presence of 0.2 M KCl. The distance from the surface of sigma subunit to the rifampicin binding site was calculated to be 27--38 A for a model having a randomly distributed and oriented array of donors on the surface of a spherical sigma subunit of 31-A radius. Our results indicate that rifampicin does not inhibit the initiation of transcription by RNA polymerase through a direct interaction with sigma subunit. In addition, energy transfer measurements under low salt conditions suggest that in RNA polymerase dimer the two rifampicin binding sites are symmetric with respect to each sigma subunit.

Binding Sites↗
PubMed1976

Statistical interpretation of fluorescence energy transfer measurements in macromolecular systems.

A statistical method is presented for the interpretation of intramolecular distance measurements by the fluorescence energy transfer technique in systems for which the detailed geometries of the donor-acceptor pairs are unknown. This method enables calculation of the probability that a specified distance range corresponds to the actual distance to be measured. It makes use of the numerically calculated probability density function for the distance of interest. The two general systems considered are the single donor-acceptor pair and the multi-donor-single-acceptor transfer. In both systems, the statistical method incorporates the uncertainty in the orientation of the donor and acceptor dipoles. In addition, it can take into account the rotational mobility of the donor dipoles determined by time-dependent emission anisotropy measurements. When more than one donor is involved in the transfer process, the uncertainties associated with the number and location of individual donors and the size and shape of the donor distribution are also incorporated in calculating the distance ranges. Application of the method was demonstrated for a wide range of transfer efficiency and Ro values for the single donor-acceptor system. Specific examples are also presented for interpretation of both single donor-acceptor and multi-donor-single-acceptor energy transfer measurements performed in order to reveal the spatial relationship of the sigma subunit and the rifampicin binding site in the Escherichia coli RNA polymerase (see Wu, C.-W., Yarbrough, L. R., Wu, F. Y.-H., and Hillel, Z. (1976), Biochemistry, preceding paper in this issue). Analysis of these energy transfer data by methods which use average values of the unknown geometrical parameters of the system yielded results similar to those obtained by the statistical method. However, the statistical method represents a more realistic approach to the interpretation of energy transfer measurements since it provides information concerning the entire range of possible distances and their relative likelihood.

Energy Transfer↗
PubMed1975

Sigma cycle during in vitro transcription: demonstration by nanosecond fluorescence depolarization spectroscopy.

Studies of RNA chain initiation have suggested that the sigma subunit of Escherichia coli RNA polymerase (RNA nucleotidyltransferase; nucleosidetriphosphate: RNA nucleotidyltransferase; EC 2.7.7.6) is released from the enzyme-template complex during transcription and may be reused by another core polymerase. Nanosecond fluorescence depolarization spectroscopy was used to follow the sigma cycle. Isolated sigma subunit labeled with the fluorescent probe dansyl (DNS) chloride bound stoichiometrically to core polymerase and stimulated transcription of phage T7 DNA to the same extent as did unlabeled sigma. DNS-sigma showed an exponential fluorescence anisotropy decay corresponding to a rotational correlation time of about 100 nsec. This value was unaffected by addition of T7 DNA, but increased about 6-fold when core polymerase was added, and increased further when T7 DNA was added. Such increases are expected for the formation of molecular complexes. Using the anisotropy decays for free DNS-sigma and DNS-sigma-core enzyme bound to T7 DNA, we calculated theoretical decay curves for various mixtures of free and bound sigma. Comparison of the observed anisotropy decay with the calculated curves indicated that about 55% of DNA-sigma was released from the enzyme-T7 DNA complex in the presence of four nucleoside triphosphates under low salt conditions. Sigma release did not occur if rifampicin was added prior to addition of four nucleoside triphosphates or if only three nucleoside triphosphates were present. After sigma was released, addition of core polymerase with rifampicin reduced the free sigma to less than 15%, indicating that the released sigma was accessible to the added core enzyme. Thus these studies have provided physical evidence for the sigma cycle during in vitro transcription.

Binding Sites↗