Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Equilibrium optimization”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 1,243 records · Page 69Linked to original sources
PubMed2001

Novel approaches to cryopreservation of human pancreatic islets.

BACKGROUND: Optimized conditions for survival and function of human islets must be defined if sufficient islets are to be recovered from a single human donor pancreas to reverse type-1 diabetes after isolation, cryopreservation, and transplantation. The objective of this study was to compare the cryoprotective effect of ethylene glycol (EG) with the standard cryoprotectant, dimethyl sulfoxide (DMSO), on isolated human islet survival and function. Furthermore, the effect of different addition protocols and equilibrium concentrations of the cryoprotectants were studied. METHODS: Islets were isolated from human pancreata by using standard techniques of collagenase digestion and discontinuous Ficoll gradient purification. Aliquots of freshly isolated human islets were cryopreserved in six groups by using DMSO or EG. Cryoprotectants were added stepwise to produce a final concentration of 1.5 or 2.0 M, or added in a single step to a concentration of 1.5 M. Islets were cryopreserved by using established protocols and cultured for 48 hr at 37 degrees C before assessment of percentage of recovery and in vitro viability. RESULTS: After cryopreservation, percentage of recovery of islets was significantly higher in the group treated with 1.5 M of DMSO added in a stepwise protocol (74+/-3%, mean+/-SEM) compared with the standard 2.0 M of DMSO (62+/-4%) (P<0.05, unpaired t test, n=6). There was no difference between the recovery of islets cryopreserved with either 1.5 M of DMSO stepwise (74+/-3%) or 1.5 M of DMSO one-step (69+/-3%). Islet recovery was higher in groups treated with DMSO compared with EG, regardless of concentration of cryoprotectant or addition protocol, although the difference was significant only when comparing DMSO and EG 1.5 M one-step. Furthermore, islets treated with 1.5 M of DMSO, added either stepwise (6.0+/-0.4) or in one-step (6.5+/-0.8), had significantly higher stimulation indices compared with islets treated with the standard cryoprotectant for human islets, 2.0 M of DMSO (4.5+/-0.5) (P<0.05). CONCLUSIONS: These results demonstrate that a lower concentration of DMSO (1.5 M) allows for the cryopreservation of human islets with superior survival and preservation of function post-culture compared with 2.0 M of DMSO and various concentrations of EG.

Cryopreservation↗
PubMed2003

Solving satisfiability problems by fluctuations: the dynamics of stochastic local search algorithms.

Stochastic local search algorithms are frequently used to numerically solve hard combinatorial optimization or decision problems. We give numerical and approximate analytical descriptions of the dynamics of such algorithms applied to random satisfiability problems. We find two different dynamical regimes, depending on the number of constraints per variable: For low constraintness, the problems are solved efficiently, i.e., in linear time. For higher constraintness, the solution times become exponential. We observe that the dynamical behavior is characterized by a fast equilibration and fluctuations around this equilibrium. If the algorithm runs long enough, an exponentially rare fluctuation towards a solution appears.

Journal Article↗
PubMed1989

Intracellular polymerization. Disease severity and therapeutic predictions.

The extent of intracellular polymerization of hemoglobin S, leading to loss of erythrocyte deformability and eventual morphological sickling, is primarily determined by oxygen saturation and intracellular hemoglobin concentration and composition. Epidemiological analysis of sickle cell disease severity among the sickle syndromes and studies of the biophysics of intracellular polymerization were used to estimate the potential clinical benefit of various therapeutic strategies. These strategies include those designed to increase deoxyhemoglobin S solubility; to increase erythrocyte volume or water content, thereby reducing the intracellular hemoglobin concentration; or, most recently, to decrease the proportion of hemoglobin S by increasing the amount of non-S hemoglobin. Increasing levels of hemoglobin F is of particular interest due to its "sparing" effect in inhibiting polymerization, the well-characterized epidemiological associations of high levels of hemoglobin F with reduced disease severity, and recent studies of drug-induced increases in hemoglobin F. Our analyses of equilibrium polymer formation at physiological oxygen saturation values suggest that small decreases in polymer formation at intermediate levels of hemoglobin F may give rise to a small decrease in anemia (as associated with homozygous alpha-thalassemia coexistent with sickle cell anemia), but that greater reductions in polymer formation may be necessary to effect a significant improvement in disease severity. Current studies of hydroxyurea-induced increases of hemoglobin F give cautious optimism that therapeutically useful levels may be attainable.

Anemia, Sickle Cell↗
PubMed2001

Osmotic and cryoprotectant permeation characteristics of islet cells isolated from the newborn pig pancreas.

The development of effective protocols for the low-temperature banking of pancreatic islets is an important step in islet transplantation for the treatment of type I diabetes mellitus. We have been exploring the use of islets from the newborn pig as an alternative source of tissue for transplantation. Current cryopreservation protocols are empirically derived, but may be optimized by modeling osmotic responses during the cryopreservation process. This study determined the osmotic and cryoprotectant permeability parameters of cells isolated from the pancreas of newborn pigs. Key parameters are: the osmotically inactive fraction of cell volume, hydraulic conductivity, the permeability coefficients of dimethyl sulfoxide (DMSO) and ethylene glycol (EG) at varying temperatures, and the activation energies of these transport processes. Newborn pig islets were dispersed into single cells and kinetic and equilibrium cell volumes were recorded during osmotic excursions using an electronic particle counter interfaced to a computer. Data were fitted to theoretical descriptions of the osmotic responses of cells, based on the Kedem-Katchalsky approach. The hydraulic conductivity (Lp) in the absence of cryoprotectant was calculated as 0.050 +/- 0.005, 0.071 +/- 0.006, and 0.300 +/- 0.016 microm/min/atm at 4 degrees C, 10 degrees C, and 22 degrees C, respectively (mean +/- SEM, n = 7, 6, or 9). These values give an activation energy value of 16.69 kcal/mol when put into an Arrhenius plot. The solute permeability (Ps) values for 1 M DMSO were 0.89 +/- 0.12, 1.86 +/- 0.28, and 5.33 +/- 0.26 microm/min at 4 degrees C, 10 degrees C, and 22 degrees C, respectively (n = 11, 8, or 10) giving an activation energy of 15.98 kcal/mol. The Lp values for cells exposed to 1 M DMSO were 0.071 +/- 0.006, 0.084 +/- 0.008, and 0.185 +/- 0.014 microm/min/atm at 4 degrees C, 10 degrees C, and 22 degrees C, respectively. The activation energy for these values was 8.95 kcal/mol. The Ps values for 2 M DMSO were 1.11 +/- 0.13, 1.74 +/- 0.19, and 7.68 +/- 0.12 microm/min for the same temperatures, with a calculated activation energy of 17.89 kcal/mol. The Lp values in the presence of 2 M DMSO were 0.070 +/- 0.006, 0.085 +/- 0.008, and 0.192 +/- 0.009 microm/min/atm at 4 degrees C, 10 degrees C, and 22 degrees C, respectively, with an activation energy of 9.40 kcal/mol. Solutions of 1 M EG gave Ps values of 1.01 +/- 0.13, 1.45 +/- 0.25, and 4.90 +/- 0.48 microm/min at the three test temperatures. The resulting activation energy was 14.60 kcal/mol. The corresponding Lp values were 0.071 +/- 0.007, 0.068 +/- 0.006, and 0.219 +/- 0.012 microm/min/atm with an activation energy of 10.96 kcal/mol. The solute permeabilities in the presence of 2 M EG for newborn pig islet cells were 1.03 +/- 0.15, 1.42 +/- 0.23, and 5.56 +/- 0.22 microm/min; the activation energy was 15.70. The Lp values for cells in the presence of 2 M EG were 0.068 +/- 0.008, 0.071 +/- 0.006, and 0.225 +/- 0.010 microm/min/atm; the activation energy for these values was 11.49 kcal/mol. These key cryobiological parameters permit the mathematical modeling of osmotic responses of intact islets during the cryopreservation process, which may lead to further improvements in the low temperature storage of islets from newborn pigs.

Animals↗
PubMed1980

Comparison of the R-3327H rat prostatic adenocarcinoma to human benign prostatic hyperplasia and metastatic carcinoma of the prostate with regard to steroid hormone receptors.

Quantitative analyses of cytosolic steroid hormone receptors were performed on nine tumors from the transplantable rat prostatic adenocarcinoma R-3327H. Androgen receptors and estrogen receptors were found in eight of nine and five of six tumors, respectively. None of the tumours analyzed contained detectable progestin or glucocorticoid receptors (four and seven tumors, respectively). The apparent equilibrium dissociation constants for the androgen and estrogen receptors were 0.7-4.3 nM and 0.6-1.8 nM, respectively. The apparent equilibrium Bmax values (maximum number of binding sites) were 1,500-25,000 fmoles/gm tissue for the androgen receptor and 640 to 5,800 fmoles/gm tissue for the estrogen receptor. A comparison between the receptor contents of the R-3327H rat tumor and human benign prostatic hyperplasia and metastatic carcinoma of the prostate showed that the rat tumor was different from the human tissues in several respects. Hence, the search for an optimal animal model for prostatic carcinoma in man must be continued.

Adenocarcinoma↗
PubMed1996

Parametric analysis of the inductively coupled plasma.

A systematic parametric study of an LTE (local thermodynamic equilibrium) mathematical model of pure inductively coupled argon plasma (ICAP) used for spectrochemical purposes was performed by means of computer simulations. The spatial distributions of temperature, gas velocity, magnetic field and energy losses were investigated under typical plasma operating conditions as function of the ICAP geometrical dimensions and dynamic parameters. These theoretical calculations can be used to predict the properties of the applied plasma in the course of practical work, to choose the optimal conditions by changing the operating parameters and to interpret existing analytical results.

Journal Article↗
PubMed2006

Equilibrium theory based design of simulated moving bed processes for a generalized Langmuir isotherm.

In the frame of the local equilibrium theory of chromatography, design criteria for complete separation of binary mixtures in simulated moving bed (SMB) separations are developed, presented and discussed. These apply to systems, whose retention behavior is characterized by a generalized Langmuir isotherm. By allowing for negative terms in the denominator of the classical Langmuir isotherm, this newly introduced adsorption model captures a broad class of competitive or synergistic adsorption, including anti-Langmuir behavior for both adsorbates, and mixed cases where one species behaves in a Lagmuirian and the other in an anti-Langmuirian manner. By extending classical equilibrium theory results for the binary Langmuir isotherm, and by generalizing the approach followed earlier to derive SMB design criteria for the binary and multi-component Langmuir isotherm, exact algebraic equations for the boundary of the complete separation region in the operating parameter space are derived for all possible generalized Langmuir isotherm. The effect of changing feed composition on the shape of the complete separation region and on the position of the optimal operating point is analyzed and discussed.

Chromatography↗
PubMed1975

DNA-protein interactions of the rat liver non-histone chromosomal protein.

Native rat liver NHC protein-DNA interactions have been investigated by use of a nitrocellulose filter assay sensitive in detection of protein-DNA complexes. Optimal conditions for DNA-protein interactions occurs at low ionic strength conditions (110 mM phosphate buffer). A fraction of NHC proteins was enriched 25-fold by their affinity for rat DNA immobilized on cellulose columns under these conditions. At higher ionic strength (260 mM-0.04M phosphate buffer and 0.15 M sodium chloride), this fraction binds approximately sevenfold less to rat DNA but with a substantial increase in stability of the complexes. Equilibrium competition experiments indicate that at the higher ionic strength there is a considerable DNA sequence specificity of the rat DNA binding NHC protein. Since rat DNA contains three components as defined by their reassociation kinetics: single copy DNA (C0t1/2pure = 1.6 times 103); middle repetitive DNA (C0t1?1PURE = 1.1); and highly repetitive (C0t1/2pure smaller than 0.02). The two former were isolated and employed in the DNA binding assays. At the high ionic strength criterion, the rat DNA binding NHC proteins showed a substantial preference for a subset of middle repetitive DNA sequences. This suggests a preferential interaction between a class of NHC proteins and a class of middle repetitive DNA sequences.

Animals↗
PubMed2006

Thermodynamic stability of a cold-adapted protein, type III antifreeze protein, and energetic contribution of salt bridges.

A thermodynamic analysis of a cold-adapted protein, type III anti-freeze protein (AFP), was carried out. The results indicate that the folding equilibrium of type III AFP is a reversible, unimolecular, two-state process with no populated intermediates. Compared to most mesophilic proteins whose folding is two-state, the psychrophilic type III AFP has a much lower thermodynamic stability at 25 degrees C, approximately 3 kcal/mol, and presents a remarkably downshifted stability-temperature curve, reaching a maximum of 5 kcal/mol around 0 degrees C. Type III AFPs contain few and non-optimally distributed surface charges relative to their mesophilic homologs, the C-terminal domains of sialic acid synthases. We used thermodynamic double mutant cycles to evaluate the energetic role of every surface salt bridge in type III AFP. Two isolated salt bridges provided no contribution to stability, while the Asp36-Arg39 salt bridge, involved in a salt bridge network with the C-terminal carboxylate, had a substantial contribution (approximately 1 kcal/mol). However, this contribution was more than counteracted by the destabilizing effect of the Asp36 carboxylate itself, whose removal led to a net 30% increase in stability at 25 degrees C. This study suggests that type III AFPs may have evolved for a minimally acceptable stability at the restricted, low temperature range (around 0 degrees C) at which AFPs must function. In addition, it indicates that salt bridge networks are used in nature also for the stability of psychrophilic proteins, and has led to a type III AFP variant of increased stability that could be used for biotechnological purposes.

Algorithms↗
PubMed2002

The synthesis and radiolabeling of 2-nitroimidazole derivatives of cyclam and their preclinical evaluation as positive markers of tumor hypoxia.

UNLABELLED: The cyclam ligand (1,4,8,11-tetraazacyclotetradecane) was condensed with various azomycin-containing synthons to produce chemical compounds that could chelate radioactive metals. It was expected that these radiolabeled markers would become bound selectively to hypoxic cells on the bioreduction of their azomycin substituent. METHODS: The markers were radiolabeled with (99m)Tc, (67)Cu, or (64)Cu. Their uptake and binding to tumor cells in vitro was characterized as a function of time and oxygen concentration. These data defined the hypoxia-specific factor, the ratio of the initial rate of marker binding to severely hypoxic relative to aerobic cells. In addition, the concentration of oxygen (in the equilibrium gas phase) that inhibited binding to 50% of the maximum rate was determined. The in vivo biodistribution and clearance kinetics of the favorable markers were investigated with severe combined immune deficiency mice bearing EMT-6 tumors whose radiobiologic hypoxic fraction (RHF) was approximately 40%. The specific activity (percentage injected dose per gram [%ID/g]) in normal and tumor tissue and the tumor-to-blood and tumor-to-muscle ratios of the optimal markers were also measured for Dunning prostate carcinomas of anaplastic (RHF = 15%-20%) and well-differentiated (RHF < 1%) histology growing in Fischer X Copenhagen rats. Planar images were acquired with some markers from these tumor-bearing rats. RESULTS: The tumor uptake of these cyclam-based markers is approximately 10 times higher when they are labeled with copper isotopes than when labeled with (99m)Tc. FC-327 and FC-334, di-azomycin-substituted cyclams, exhibited hypoxia-specific factors > or = 7.0. The oxygen concentration that inhibited their binding to 50% of the maximal rate was approximately 0.5% O(2), similar to that of the radiobiologic oxygen effect. The %ID/g of (64)Cu-FC-334 retained in EMT-6 tumors in mice and in the anaplastic and well-differentiated prostate tumors in rats 6 h after administration was approximately 6.5, 0.4, and 0.1, respectively. Marker activity in tumor was always less than that in liver and kidney. The tumor-to-blood and tumor-to-muscle ratios of (64)Cu-FC-327 and (64)Cu-FC-334 activity in R3327-AT tumor-bearing rats are higher than those observed for (64)Cu-di-acetyl-bis (N(4)-methylthiosemicarbazone) and approach those of beta-D-(125)I-iodinated azomycin galactopyranoside, the optimal hypoxia marker of the azomycin-nucleoside class. CONCLUSION: These data suggest that some azomycin-cyclams exhibit good hypoxia-marking potential to tumor cells in vitro and to animal tumors of known RHF. Both PET and SPECT could be used to image tumor hypoxia with markers labeled with (64)Cu and (67)Cu, respectively.

Animals↗
PubMed2005

Speciation through competition: a critical review.

We examined causes of speciation in asexual populations in both sympatry and parapatry, providing an alternative explanation for the speciation patterns reported by Dieckmann and Doebeli (1999) and Doebeli and Dieckmann (2003). Both in sympatry and parapatry, they find that speciation occurs relatively easily. We reveal that in the sympatric clonal model, the equilibrium distribution is continuous and the disruptive selection driving evolution of discrete clusters is only transient. Hence, if discrete phenotypes are to remain stable in the sympatric sexual model, there should be some source of nontransient disruptive selection that will drive evolution of assortment. We analyze sexually reproducing populations using the Bulmer's infinitesimal model and show that cost-free assortment alone leads to speciation and disruptive selection only arises when the optimal distribution cannot be matched--in this example, because the phenotypic range is limited. In addition, Doebeli and Dieckmann's analyses assumed a high genetic variance and a high mutation rate. Thus, these theoretical models do not support the conclusion that sympatric speciation is a likely outcome of competition for resources. In their parapatric model (Doebeli and Dieckmann 2003), clustering into distinct phenotypes is driven by edge effects, rather than by frequency-dependent competition.

Biological Evolution↗
PubMed1975

Factors affecting the reassociation and reactivation of the half-molecular weight nonidentical subunits of pigeon liver fatty acid synthetase.

The pigeon liver fatty acid synthetase complex (14 S) is dissociated in low ionic strength buffer containing dithiothreitol to form a half-molecular weight subunits (9 S) which are completely inactive for the synthesis of saturated fatty acids. The dithiothreitol-protected (reduced) subunits are rapidly reassociated and reactivated to form the active enzyme complex, not only by an increase in salt concentration but also by micromolar concentrations of NADP+ or NADPH. Increases in KCl or NADPH concentration result in an increase in the extent of reactivation (equilibrium) with no change in the over-all rate of the reaction or the half-life ofreactivation of the enzyme. The extent (equilibrium) of reactivation of the enzyme is the same in 0.2 M potassium phosphate buffer, pH 7.0; 0.2 M KCl in 5 mM Tris-35 mM glycine buffer, PH 8.3; and 50 muM NADP+ or NADPH in the Tris-glycine buffer. The extent and rate of reactivation of the enzyme is dependent not only on ionic strength and NADPH concentration, but also on pH and temperature. Reactivation with 0.2 M KCl is optimal between pH 7.3 and 8.5. At higher and lower pH values the rate and extent of reactivation are lowered. The rate and extent of reactivation are also decreased as the temperature is lowered below 10 degrees. At 0 degrees there is little reactivation of enzyme activity. However, in the presence of 0.2 M KCl containing 15 to 40% glycerol at 0 degrees, reactivation of the enzyme is about 50% complete. The rate of reactivation of enzyme in the presence of KCl or NADPH conforms to first order kinetics. This result suggests that the subunits first combine to form an inactive complex which is subsequently transformed to an enzymatically active complex. Evidence for the presence of inactive complex was obtained in experiments carried out in 0.2 M KCl at pH 6.0, and in 0.2 M KCl at pH 8.3, at both 6 and 3 degrees. Under these conditions the amount of complex observed upon ultracentrifugation was greater than expected from determinations of enzyme activity. The above findings suggest that ionic and hydrophobic interactions, and possibly the water structure surrounding the interacting sites, are of prime importance in reassociation and reactivation of enzyme. In addition, NADP+ and NADPH have very specific effects in bringing about reassociation and in maintaining the structural integrity of the multienzyme complex.

Animals↗
PubMedDate not supplied

[Combined immobilized cultures producing fibrinolytic proteinases].

The authors obtained combined immobilised systems composed of a culture producing fibrinolytic proteinases and a stimulating strain. The optimal ratio between the two cultures in gel was selected at a high starting cell density. Highly stable immobilised cultures were produced by growing the cells in gel particles. The interrelationship of the partners was studied in the binary immobilised culture. The biosynthetic activity of the system fell down to the level of a monoculture when the cells of the stimulating strain were eliminated from gel. The producing and stimulating strains are at equilibrium in associative immobilised cultures obtained by growing the cells in gel, and Arthrobacter is not eliminated. The mechanism of biosynthesis stimulation in a combined immobilised culture has been studied. Apparently, the procedure of immobilisation and the action of a stimulating compound exert the synergistic effect.

Arthrobacter↗
PubMed1994

Kinetic properties of monogalactosyldiacylglycerol synthase from spinach chloroplast envelope membranes.

We have investigated the functioning of monogalactosyldiacylglycerol (MGDG) synthase activity partially purified from spinach chloroplast envelope membranes, using mixed micelles containing diacylglycerol (the substrate for MGDG synthase), CHAPS (3-[(cholamidopropyl)dimethylammonio]-1- propanesulfonic acid), and phosphatidylglycerol. The presence of this anionic phospholipid was essential for optimal MGDG synthase activity because it strongly improves diacylglycerol solubilization by CHAPS. We have demonstrated that the "surface dilution" kinetic model proposed by Deems et al. (Deems, R.A., Eaton, B.R., and Dennis, E.A. (1975) J. Biol. Chem. 250, 9013-9020) is valid for MGDG synthase assayed in mixed micelles within a narrow range of CHAPS concentration. However, the experimental conditions we have set up in this study led to the description of defined equilibrium and kinetic parameters of the interaction of the envelope MGDG synthase with diacylglycerol. Two-substrate kinetic studies were performed with varied UDP-galactose molar concentrations and varied dioleoylglycerol surface concentrations. The families of reciprocal plots obtained were shown to intersect at a single point of the 1/[substrate] axis thus demonstrating that MGDG synthase is a sequential, either random or ordered, bireactant system. Therefore, MGDG synthase possesses two distinct and independent substrate-binding sites, a hydrophilic one for UDP-galactose and a hydrophobic one for diacylglycerol. The dependence of kinetic parameters on the diacylglycerol mol fraction allows a comparison of the affinity of the enzyme for a wide range of diacylglycerol molecular species. The Km values obtained were ranging between 0.0089 mol fraction (52 microM) for dilinoleoylglycerol (18:2/18:2) to 0.0666 mol fraction (416 microM) for distearoylglycerol (18:0/18:0), but the differences observed were not really related to the unsaturation of the molecule since the Km value for dilinoleoylglycerol was much lower than that (0.040 mol fraction) for dilinoleoylglycerol (18:3/18:3). The Km values for dioleoylglycerol (18:1/18:1) and for the diacylglycerol molecular species synthesized within chloroplasts, i.e. containing 18:1/16:0, were in the average range, i.e. lower than 0.030 mol fraction (around 170 microM).

Chloroplasts↗
PubMed1995

High-frequency jet ventilation in endolaryngeal surgery.

STUDY OBJECTIVE: To describe the clinical experience with high-frequency jet ventilation (HFJV) of the lungs during endolaryngeal surgery and its effect on acid-base balance and capillary PO2 (PcO2), PCO2, central hemodynamics, and tracheobronchial mucous membrane. DESIGN: Evaluation of different modalities of HFJV. SETTING: Operating rooms and otolaryngology intensive care unit in a medical institute. PATIENTS: 218 patients undergoing elective endolaryngeal surgery. INTERVENTIONS: Patients receive HFJV through catheters with an inner diameter of 1.4 to 1.8 mm. Catheters were introduced orotracheally, nasotracheally, percutaneously, or through a fenestrated tracheostomy tube. Minute volume was based on body weight times 0.2, corrected for acid-base balance. MEASUREMENTS AND MAIN RESULTS: Intraoperative cardiac output, airway pressure, changes in tracheobronchial mucosa, and acid-base balance were monitored. HFJV changed central hemodynamics slightly and preserved gas exchange: PcCO2 remained within normal limits, while PcO2 increased. Use of thin catheters enhanced largyneal exposure and surgical manipulation. Percutaneous catheterization permitted resumption of HFJV in the event of laryngeal edema and inadequate spontaneous respiration after surgery. CONCLUSION: HFJV leads to optimal conditions for endolaryngeal surgery, reverses constant outflow of the respiratory gas mixture, prevents aspiration of tissue products and blood, and removes smoke from the operative site when using laser surgery.

Acid-Base Equilibrium↗
PubMed1991

An optimal viral peptide recognized by CD8+ T cells binds very tightly to the restricting class I major histocompatibility complex protein on intact cells but not to the purified class I protein.

CD8+ cytotoxic T lymphocytes recognize cell surface complexes formed by class I major histocompatibility complex (MHC-I) glycoproteins and antigenic peptides. We have identified a peptide nonamer (termed IV9) derived from the human immunodeficiency virus that is over a millionfold more active (at subpicomolar concentrations) than peptide analogues longer or shorter by one or two amino acid residues. Although IV9 does not detectably bind to isolated MHC-I molecules as measured by equilibrium dialysis, we quantitated its specific binding in unaltered form to MHC-I on intact cells. Less than 1% of cell surface MHC-I forms complexes with IV9, which suffices to trigger maximal cytotoxic T-lymphocyte activity. By contrast, a peptide dodecamer that includes the IV9 sequence and is active at micromolar concentrations does not bind to MHC-I on intact cells, raising the possibility that this longer peptide undergoes processing. Using stoichiometrically iodinated IV9 to obviate the ambiguities associated with trace labeling methods, we measured the dissociation kinetics of purified peptide/MHC-I complexes isolated by affinity chromatography and found these complexes to be exceedingly stable (t1/2 = 200-600 hr).

Amino Acid Sequence↗
PubMed1988

Pneumoperitoneum induced pH changes in follicular and Douglas fluids during laparoscopic oocyte retrieval in humans.

The effects of different insufflation media gases for pneumoperitoneum on the acidity of follicular fluid and blood acid--base balance were studied in two groups of patients during laparoscopic oocyte retrieval. Insufflation with 100% CO2 was compared with insufflation with 5% CO2 in air. End-tidal CO2 and the acid-base status of arterial blood, follicular and Douglas fluids were evaluated. When using 5% CO2 in air as insufflation gas, pH values and pCO2 levels observed in the aspirated follicular (pH: 7.35 +/- 0.06, pCO2: 38.8 +/- 4.5 mmHg) and Douglas fluid (pH: 7.40 +/- 0.07, pCO2: 38.5 +/- 6.2 mmHg) remained normal. With 100% CO2 insufflation, the follicular fluid pH (7.22 +/- 0.07) and pCO2 (53.1 +/- 10.9 mmHg) and the Douglas fluid pH (6.99 +/- 0.12) and pCO2 (90.3 +/- 18.4 mmHg) were grossly disturbed and outside the physiological range. No differences occurred in pO2 or HCO3 levels. These data suggest that pneumoperitoneum with 5% CO2 in air provides more optimal environmental conditions for oocytes used for in-vitro fertilization. However, further investigations on large patient groups are required to demonstrate whether such environmental conditions influence the success rate of in-vitro fertilization in humans.

Acid-Base Equilibrium↗
PubMed2001

Cardiopulmonary bypass and cerebral injury in adults.

Cerebral injury after cardiac surgery is still a major cause of mortality and morbidity after cardiac surgery. In an aging patient population the incidence is likely to increase. Comparisons between cardiac and other major surgery suggested that cardiopulmonary bypass (CPB) causes the neurological sequelae. Strategies to avoid brain injury target the reduction of emboli floating in the cerebral circulation, adequacy of cerebral oxygenation, and minimization of the whole body inflammatory response to the bypass circuit. Experimental and clinical studies demonstrated that manipulation of CPB can reduce abundant cerebral blood flow and the embolic load to the brain. Hematocrit, temperature, blood pressure, and acid-base status during CPB are parameters that have impact on the neurological outcome and can be optimized. Other possibilities to avoid cerebral complications include improvements of surgical techniques and devices or the application of new therapeutic drugs. However, further experimental studies and, most importantly, prospective randomized clinical trials are warranted to prove new innovative concepts in clinical practice.

Acid-Base Equilibrium↗