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PubMed1986

Condensation of chromatin: role of multivalent cations.

We have used electric dichroism to investigate the influence of multivalent cations upon the compaction of chicken erythrocyte chromatin from the unfolded, 10-nm fiber to the 30-nm solenoid and subsequent aggregation. The pattern of condensation, which consists of compaction plus aggregation, is found to be strikingly similar for a variety of cations of differing charge, including the physiologically important polyamines spermine and spermidine. With a few exceptions such as Cu2+ and Gd3+, an optimally compacted fiber with reproducible hydrodynamic properties is produced prior to the onset of aggregation. We report the concentrations of di-, tri-, and tetravalent cations required for optimal condensation; in addition, for tri- and tetravalent cations, we were able to estimate the extent of charge neutralization produced by their binding to the optimally compacted fiber. The results show that the multivalent ion concentration required for optimal compaction decreases as cationic charge increases. In addition, the effect of a mixture of dilute mono- and multivalent cations on chromatin condensation is synergistic, rather than competitive as has been found for the multivalent cation induced condensation of DNA or the B----Z conformational transition. A simple calculation indicates that the entropy of ion uptake in chromatin condensation is surprisingly constant for a range of ionic conditions; this factor may be a dominant one in determining the folding equilibrium.

Animals↗
PubMed1999

Coordination Chemistry, Structure, and Reactivity of Thiouracil Derivatives of Tungsten(0) Hexacarbonyl: A Theoretical and Experimental Investigation into the Chelation/Dechelation of Thiouracil via CO Loss and Addition.

The synthesis of 2-thiouracil and 6-methyl-2-uracil derivatives of tungsten carbonyl from the reaction of photogenerated W(CO)(5)(solvent) (solvent = MeOH or THF) and the corresponding [Et(4)N][thiouracilate] is described. The crystal structure of the [Et(4)N][W(CO)(5)(2-thiouracilate)], 1, derivative is reported where the thiouracilate is found to be bound to the tungsten center via the exocyclic sulfur atom. In the solid-state structure of 1 two anions are associated by means of two hydrogen bonds between the metal bound nucleobases. These pentacarbonyl complexes stereoselectively lose cis carbonyl ligands, as is apparent from (13)C-labeling studies, to provide the endocyclic nitrogen N(1)-chelated tungsten tetracarbonyl derivatives, e.g., [Et(4)N][W(CO)(4)(2-thiouracilate)], 3. The kinetics of the loss of CO from the pentacarbonyl anions to afford the metal tetracarbonyls, and the reverse of that process, were monitored by means of in situ infrared spectroscopy in the nu(CO) region as a function of temperature. These studies reveal that the tetracarbonyl anions in CO-saturated acetonitrile ([CO] approximately 6 x 10(-)(3) M) are unstable with respect to the formation of the pentacarbonyl derivatives, i.e., the equilibrium 1 right harpoon over left harpoon 3 + CO lies to the left under an atmosphere of carbon monoxide. From the activation parameters determined for the dissociative CO loss process (DeltaH() = 82.0 +/- 3.6 kJ mol(-)(1) and DeltaS() = -44.9 +/- 9.6 J mol(-)(1) K(-)(1) for complex 1) it is apparent that the sulfur-bound thiouracilate ligand is serving as a pi-donor during CO dissociation, i.e., behaving as a cis-labilizing ligand. Ab initio geometry optimizations carried out for the process 1 right harpoon over left harpoon 3 + CO at the Hartree-Fock and DFT levels support these experimental observations. For example, complex 1 is shown to be more stable than 3 + CO and chelation via the endocyclic N(1) donor is favored over N(3) binding. Finally, the "16-electron" intermediate resulting from CO dissociation in 1 was found to possess a significantly shortened W-S interaction, presumably due to the pi-donating ability of the thiouracilate ligand.

Journal Article↗
PubMed1979

Purification and some properties of cholesterol oxidase from Schizophyllum commune with covalently bound flavin.

Cholesterol oxidase [EC 1.1.3.6] from Schizophyllum commune was purified by an affinity chromatography using 3-O-succinylcholesterol-ethylenediamine (3-cholesteryl-3-[2-aminoethylamido]propionate) Sepharose gels. The resulting preparation was homogeneous as judged by sodium dodecyl sulfate (SDS) polyacrylamide gel electrophoresis. The molecular weight of the enzyme was estimated to be 53,000 by SDS-gel electrophoresis and 46,000 by sedimentation equilibrium. The enzyme contained 483 amino acid residues as calculated on the basis of the molecular weight of 53,000. The enzyme consumed 60 mumol of O2/min per mg of protein with 1.3 mM cholesterol at 37 degrees C. The enzyme showed the highest activity with cholesterol; 3 beta-hydroxysteroids, such as dehydroepiandrosterone, pregnenolone, and lanosterol, were also oxidized at slower rates. Ergosterol was not oxidized by the enzyme. The Km for cholesterol was 0.33 mM and the optimal pH was 5.0. The enzyme is a flavoprotein which shows a visible absorption spectrum having peaks at 353 nm and 455 nm in 0.1 M acetate buffer, pH 4.0. The spectrum was characterized by the hypsochromic shift of the second absorption peak of the bound flavin. The bound flavin was reduced on anaerobic addition of a model substrate, dehydroepiandrosterone. Neither acid not heat treatment released the flavin coenzyme from the enzyme protein. The flavin of the enzyme could be easily released from the enzyme protein in acid-soluble form as flavin peptides when the enzyme protein was digested with trypsin plus chymotrypsin. The mobilities of the aminoacyl flavin after hydrolysis of the flavin peptides on thin layer chromatography and high voltage electrophoresis differed from those of free FAD, FMN, and riboflavin. A pKa value of 5.1 was obtained from pH-dependent fluorescence quenching process of the aminoacyl flavin. AMP was detected by hydrolysis of the flavin peptides with nucleotide pyrophosphatase. The results indicate strongly that cholesterol oxidase from Schizophyllum commune contains FAD as the prothetic group, which is covalently linked to the enzyme protein. The properties of the bound FAD were comparable to those of N (1)-histidyl FAD.

3-Hydroxysteroid Dehydrogenases↗
PubMed1992

Optimal association-saturation procedure for estimating association and dissociation rate parameters in receptor studies. Application to solubilized A1 adenosine receptors.

A method of obtaining estimates of the maximum binding and association and dissociation rate constants for a receptor-ligand interaction is described. This new procedure, the association-saturation method, is based on an exact mathematical equation which defines the model without simplifications. The method proposed is readily applicable to any system consisting of one ligand and one receptor. With only four determinations, each involving one ligand concentration and an association time, it is possible to determine the number of specific binding sites, the dissociation and association rate constants and the equilibrium dissociation constant with accuracy. No dissociation curve is required, and only one point of the association curve for each ligand concentration is necessary. In addition to the higher confidence in the estimates of the parameter values obtained, this method leads to important savings in radiolabelled compounds and experimental time. The results were compared with those obtained with standard association-dissociation curves and saturation isotherms. The optimum number of replicates of each experimental point to obtain reliable estimates of different parameters is discussed on the basis of simulation studies. The performance of the procedure is analysed by means of association-saturation experiments with the agonist [adenine-2,8-3H,ethyl-2-3H]N6-phenylisopropyladenosine and solubilized A1 adenosine receptors from pig brain cortex.

Animals↗
PubMed1997

Acid-base balance and O2 transport at high altitude.

Ear lobe blood pHa, PaCo2, PaO2, and O2 saturation (SaO2) were measured in healthy Caucasians and Sherpas at 3400 m (Namche Bazaar, Nepal, n = 4/5), 5050 m (Pyramid Laboratory, Lobuche, Nepal, n = 20/5) and 6450 m (Camp II of Mt Everest, n = 11/7). In the investigated altitude range, pHa increased progressively with altitude from 7.463 +/- 0.005 (mean +/- SE) to 7.496 +/- 0.006 in Caucasians whereas it remained essentially constant (7.45-7.46) in Sherpas. At all altitudes, PaCO2 was higher in Sherpas than in Caucasians (P < 0.02). By contrast, PaO2 and SaO2 were the same in Caucasians and Sherpas at all investigated altitudes. Moreover, in Caucasians sojourning for 3 weeks at 5050 m, PaCO2 kept decreasing whereas pHa, PaO2 and SaO2 remained constant. These data suggest that; (1) respiratory alkalosis was a common finding both in Caucasians and Sherpas; (2) at 6450 m. Sherpas were less alkalotic due to higher PaCO2 than Caucasians, possibly a consequence of a blunted ventilatory response; (3) at 6450 m, SaO2 and PaO2 were the same in Caucasians and Sherpas despite different PaCO2 values. The latter finding could be the consequence of one or more of the following adjustments in Sherpas: (1) an increased efficiency of alveolar O2 transfer, i.e. smaller alveolar-arterial O2 gradient; (2) a decreased (arterial-mixed venous) O2 difference possibly due to increased cardiac output; (3) a reduced increase of the [2,3-DPG]/[Hb] ratio; but not (4) an elevated gas exchange ratio (R). It is concluded that both physiological and biochemical variables contribute to optimize the O2 transport at altitude. Apparently a more efficient adaptation to hypoxia allows Sherpas to limit alkalosis through a lower ventilatory drive and to maintain SaO2 at the same PaO2 by decreasing the [2,3-DPG]/[Hb] ratio.

2,3-Diphosphoglycerate↗
PubMed2002

End-tidal CO2-derived values during emergency trauma surgery correlated with outcome: a prospective study.

BACKGROUND: The purpose of this study was to determine whether end-tidal carbon dioxide (PETCO) derived variables assist in evaluating the adequacy of resuscitation during emergency surgery for trauma. METHODS: This was a prospective study of end-tidal derived variables and outcome in 106 trauma patients in an urban Level I trauma center. RESULTS: The patients who lived (compared with those who died) had higher final end-tidal Pco levels, lower arterial-end tidal CO differences (Pa-ET)CO, and a decreased alveolar dead space ratio (p < 0.001). The best survival rates were with a PETCO > 27 mm Hg, a (Pa-ET)CO < or = 9 mm Hg, and 96% (56 of 58) for an alveolar dead space ratio < or = 0.20 (p < 0.001). An inappropriately high or "excess Paco also correlated with a decreased (Pa-ET)CO and poorer prognosis. If, after the initial resuscitation, the PETCO -derived values did not achieve these "optimal" levels, survival was significantly reduced. CONCLUSION: During emergency trauma surgery, the PETCO and its derived values help to predict outcome and may be used to identify patients needing more aggressive resuscitation.

Acid-Base Equilibrium↗
PubMed2006

A multiple chemical equilibria approach to modeling and interpreting the separation of amino acid enantiomers by chiral ligand-exchange chromatography.

A model of chiral ligand-exchange chromatography (CLEC) is presented that combines the non-ideal equilibrium-dispersion equation for solute transport with equations describing all chemical equilibria within the column. The model connects elution band profiles to the time and space resolved formation of diastereomeric complexes in both the mobile and stationary phases, thereby providing insights into the overall separation mechanism. The stoichiometries and formation constants for all equilibrium complexes formed in the mobile phase are taken from standard thermodynamic databases and independent potentiometric titration experiments. Formation constants for complexes formed with the stationary phase ligand are determined from potentiometric titration data for a water-soluble analogue of the ligand. Together this set of pure thermodynamic parameters can be used to calculate the equilibrium composition of the system at any operating condition. The model includes a temperature-dependent pure-component parameter, determined by regression to a single elution band for the pure component, that corrects for subtle effects associated with immobilizing the ligand (i.e., the chiral selector) onto the stationary phase. Model performance is assessed through comparison with chromatograms for two hydrophobic amino acid racemates loaded on the Nucleosil Chiral-1 CLEC column. The model is also applied to a restricted optimization of column operating conditions to assess its predictive power. In both cases, model predictions compare well with experiment while also providing a molecular understanding of the separation process and its dependence on column operating conditions.

Amino Acids↗
PubMed2006

Selection intensity on preferred codons correlates with overall codon usage bias in Caenorhabditis remanei.

Adaptive codon usage provides evidence of natural selection in one of its most subtle forms: a fitness benefit of one synonymous codon relative to another. Codon usage bias is evident in the coding sequences of a broad array of taxa, reflecting selection for translational efficiency and/or accuracy as well as mutational biases. Here, we quantify the magnitude of selection acting on alternative codons in genes of the nematode Caenorhabditis remanei, an outcrossing relative of the model organism C. elegans, by fitting the expected mutation-selection-drift equilibrium frequency distribution of preferred and unpreferred codon variants to the empirical distribution. This method estimates the intensity of selection on synonymous codons in genes with high codon bias as N(e)s = 0.17, a value significantly greater than zero. In addition, we demonstrate for the first time that estimates of ongoing selection on codon usage among genes, inferred from nucleotide polymorphism data, correlate strongly with long-term patterns of codon usage bias, as measured by the frequency of optimal codons in a gene. From the pattern of polymorphisms in introns, we also infer that these findings do not result from the operation of biased gene conversion toward G or C nucleotides. We therefore conclude that coincident patterns of current and ancient selection are responsible for shaping biased codon usage in the C. remanei genome.

Animals↗
PubMed2000

Theoretical studies of molybdenum peroxo complexes [MoOn(O2)3-n(OPH3)] as catalysts for olefin epoxidation.

The equilibrium geometries of the molybdenum oxo/peroxo compounds MoOn(O2)3-n and the related complexes [MoOn(O2)3-n(OPH3)] and [MoOn(O2)3-n(OPH3)(H2O)] (n = 0-3) have been calculated using gradient-corrected density-functional theory at the B3LYP level. The structures of the peroxo complexes with ethylene ligands [MoOn(O2)3-n(C2H4)] and [MoOn(O2)3-n(OPH3)(C2H4)] (n = 1, 2) where ethylene is directly bonded to the metal have also been optimized. Calculations of the metal-ligand bond-dissociation energies show that the OPH3 ligand in [MoOn(O2)3-n(OPH3)] is much more strongly bound than the ethylene ligand in [MoOn(O2)3-n(C2H4)]. This makes the substitution of phosphane oxide by olefins in the epoxidation reaction unlikely. An energy-minimum structure is found for [MoO(O2)2(OPH3)(C2H4)], for which the dissociation of C2H4 is exothermic with D0 = -5.2 kcal/mol. The reaction energies for the perhydrolysis of the oxo complexes with H2O2 and the epoxidation of ethylene by the peroxo complexes have also been calculated. The peculiar stability of the diperoxo complex [MoO(O2)2(OPH3)(H2O)] can be explained with the reaction energies for the perhydrolysis of [MoOn(O2)3-n(OPH3)(H2O)]. The first perhydrolysis step yielding the monoperoxo complex is less exothermic than the second perhydrolysis reaction, but the further reaction with H2O2 yielding the unknown triperoxo complex is clearly endothermic. CDA analysis of the metal-ethylene bond shows that the binding interactions are mainly caused by charge donation from the ligand to the metal.

Journal Article↗
PubMed2006

Concentration-dependent kinetics of acetylcholinesterase inhibition by the organophosphate paraoxon.

For decades the interaction of the anticholinesterase organophosphorus compounds with acetylcholinesterase has been characterized as a straightforward phosphylation of the active site serine (Ser-203) which can be described kinetically by the inhibitory rate constant k(i). However, more recently certain kinetic complexities in the inhibition of acetylcholinesterase by organophosphates such as paraoxon (O,O-diethyl O-(p-nitrophenyl) phosphate) and chlorpyrifos oxon (O,O-diethyl O-(3,5,6-trichloro-2-pyridyl) phosphate) have raised questions regarding the adequacy of the kinetic scheme on which k(i) is based. The present article documents conditions in which the inhibitory capacity of paraoxon towards human recombinant acetylcholinesterase appears to change as a function of oxon concentration (as evidenced by a changing k(i)), with the inhibitory capacity of individual oxon molecules increasing at lower oxon concentrations. Optimization of a computer model based on an Ordered Uni Bi kinetic mechanism for phosphylation of acetylcholinesterse determined k(1) to be 0.5 nM(-1)h(-1), and k(-1) to be 169.5 h(-1). These values were used in a comparison of the Ordered Uni Bi model versus a k(i) model in order to assess the capacity of k(i) to describe accurately the inhibition of acetylcholinesterase by paraoxon. Interestingly, the k(i) model was accurate only at equilibrium (or near equilibrium), and when the inhibitor concentration was well below its K(d) (pseudo first order conditions). Comparisons of the Ordered Uni Bi and k(i) models demonstrate the changing k(i) as a function of inhibitor concentrations is not an artifact resulting from inappropriate inhibitor concentrations.

Acetylcholinesterase↗
PubMed1975

The mechanism of chlorpromazine and quinidine inhibition of cardiac sarcotubular ATPase.

Although chlorpromazine and quinidine have dissimilar chemical properties, both are negative inotropic agents and both depress the ATPase activity of cardiac sarcotubular fractions. With the aid of gamma-AT32 P we have identified the step in ATP hydrolysis which is inhibited by each of these agents. By optimizing the conditions for formation of a phosphorylated intermediate (EP) by addition of 5 mM calcium to the incubation medium we found that chlorpromazine (0.25--1 mM) severely depressed EP formation, whereas quinidine (0.25--1 mM) had no effect. After the isolation of EP we showed that chlorpromazine had no effect on the magnesium-facilitated hydrolysis of EP, whereas quinidine was a potent inhibitor of this hydrolytic step. The effects of both quinidine and chlorpromazine on the E + ATP equilibrium EP + ADP reaction were studied. Quinidine had no effect on this reaction, whereas chlorpromazine, at 1 mM, shifted the reaction toward ATP formation.

Adenosine Triphosphatases↗
PubMed2004

Homology modeling and S(N)2 displacement reaction of fluoroacetate dehalogenase from Burkholderia sp. FA1.

Fluoroacetate dehalogenase (EC 3.8.1.3) catalyzes the dehalogenation of fluoroacetate and other haloacetates. In order to investigate the relation between the structure and the function, and understand the reaction mechanism of the enzyme, a 3D model of fluoroacetate dehalogenase FAc-DEX FA1 was built by homology-based modeling. The 3D model was optimized by unconstrained molecular dynamics simulation. Furthermore, the optimized 3D model was assessed by comparison of specific properties with two known protein structures. From the final 3D model, we find that the main residues involved in the active site in FAc-DEX FA1 were Phe34, Trp148, Tyr147, Tyr212, Asp104, and His271; especially Asp104 was the key nucleophilic residue in substrate binding. A reaction model including Asp104 and the substrate fluoroacetate was then constructed and used to characterize explicit enzymatic reactions. In order to further illustrate catalytic properties, the equilibrium geometries, energies, and frequencies of stationary points (reactants, products, and transition states) of the reaction model were calculated at the B3LYP/6-31G level of theory in both gas phase and solution. The results showed that the reaction in gas was dynamically more favorable than in solution.

Amino Acid Sequence↗
PubMed2006

Experimental and ab initio study of the HO2.CH3OH complex: thermodynamics and kinetics of formation.

Near-infrared spectroscopy was used to monitor HO2 formed by pulsed laser photolysis of Cl2-O2-CH3OH-N2 mixtures. On the microsecond time scale, [HO2] exhibited a time dependence consistent with a mechanism in which [HO2] approached equilibrium via HO2 + HO2.CH3OH (3, -3). The equilibrium constant for reaction 3, K(p), was measured between 231 and 261 K at 50 and 100 Torr, leading to standard reaction enthalpy and entropy values (1 sigma) of delta(r) = -37.4 +/- 4.8 kJ mol(-1) and delta(r) = -100 +/- 19 J mol(-1) K(-1). The effective bimolecular rate constant, k3, for formation of the HO2.CH3OH complex is .10(-15).exp[(1800 +/- 500)/T] cm3 molecule(-1) s(-1) at 100 Torr (1 sigma). Ab initio calculations of the optimized structure and energetics of the HO2.CH3OH complex were performed at the CCSD(T)/6-311++G(3df,3pd)//MP2(full)/6-311++G(2df,2pd) level. The complex was found to have a strong hydrogen bond (D(e) = 43.9 kJ mol(-1)) with the hydrogen in HO2 binding to the oxygen in CH3OH. The calculated enthalpy for association is delta(r) = -36.8 kJ mol(-1). The potentials for the torsion about the O2-H bond and for the hydrogen-bond stretch were computed and 1D vibrational levels determined. After explicitly accounting for these degrees of freedom, the calculated Third Law entropy of association is delta(r) = -106 J mol(-1) K(-1). Both the calculated enthalpy and entropy of association are in reasonably good agreement with experiment. When combined with results from our previous study (Christensen et al. Geophys. Res. Lett. 2002, 29; doi:10.1029/2001GL014525), the rate coefficient for the reaction of HO2 with the complex, HO2 + HO2.CH3OH, is determined to be (2.1 +/- 0.7) x 10(-11) cm3 molecule(-1) s(-1). The results of the present work argue for a reinterpretation of the recent measurement of the HO2 self-reaction rate constant by Stone and Rowley (Phys. Chem. Chem. Phys. 2005, 7, 2156). Significant complex concentrations are present at the high methanol concentrations used in that work and lead to a nonlinear methanol dependence of the apparent rate constant. This nonlinearity introduces substantial uncertainty in the extrapolation to zero methanol.

Journal Article↗
PubMed1989

Monte-Carlo-self consistent field method in the polyelectrolyte theory.

A new time saving numerical method for calculation of equilibrium potential and density distribution of mobile ions around the polyion in a polyelectrolyte system is proposed: the region around the polyion is being divided into two zones-internal and external; in the internal zone all the ions are accounted explicity with the aid of Monte-Carlo procedure; in the external zone the combined Monte-Carlo-self consistent field method proposed earlier is applied, an exchange of ions between regions is being implied. For 1:1 electrolyte the optimal choice of the boundary between the zones has been demonstrated. As an example of a more complicated system calculation for 2:2:1:1 electrolyte was carried out.

Algorithms↗
PubMed1991

DNA-binding specificity of the fushi tarazu homeodomain.

The fushi tarazu (ftz) gene of Drosophila melanogaster encodes a homeodomain-containing transcription factor that functions in the formation of body segments. Here we report an analysis of the DNA-binding properties of the ftz homeodomain in vitro. We provide evidence that the homeodomain binds to DNA as a monomer, with an equilibrium dissociation constant of 2.5 x 10(-11) M for binding to a consensus binding site. A single ftz binding site occupies 10 to 12 bp, as judged by the ability of protein bound at one site to interfere with binding to an adjacent site. These experiments also demonstrated a lack of cooperative binding between ftz homeodomains. Analysis of single-nucleotide substitutions over an 11-bp sequence shows that a stretch of 6 bp is critical for binding, with an optimal sequence of 5'CTAATTA3'. These data correlate well with recent structural evidence for base-specific contact at these positions. In addition, we found that sequences flanking the region of direct contact have effects on DNA binding that could be of biological significance.

Animals↗
PubMed1994

Cross-linking hemoglobin by design: lessons from using molecular clamps.

The development of a red cell substitute by chemical modification of hemoglobin has been approached as a systematic, iterative process. Acyl phosphate methyl esters were designed as anionic electrophiles to permit selective acylation of amino groups in the cationic site of hemoglobin which binds polyanions. Kinetic studies with systematically substituted acyl phosphates and amines show that the reaction is controlled by a reversible addition step followed by an irreversible elimination step. Acyl phosphate methyl esters which are derivatives of rigid dicarboxylic acids introduce cross-links in human hemoglobin between amino groups in the beta subunits (epsilon-NH2-Lys-82, alpha-NH2-Val-1) and permit correlation of oxygen binding properties with cross-link structure. The data suggest that the cross-link maintains cooperativity while reducing overall oxygen affinity by lowering the affinity of the R form for oxygen rather than by perturbing the R,T equilibrium of native hemoglobin. Materials produced from deoxyhemoglobin with a cross-link between positions 1 and 82 of the two beta units have appropriate oxygen affinity for red cell substitutes. The use of a trifunctional cross-linker, trimesyl tris(methyl phosphate) selectively produces hemoglobin with the desired 1-82 connection in good yield. The reagent is readily prepared and the properties of this chemically modified hemoglobin are suitable for trial as a red cell substitute, closely resembling those of optimized materials produced by recombinant technology. Further work is producing new chemicals and providing structural information.

Binding Sites↗
PubMedDate not supplied

Radionuclide equilibrium ventriculography in infants and children using converging collimator.

In infants and young children, the radionuclide cardiac blood-pool images obtained with a general-purpose (GP) parallel-hole collimator are often too small to provide accurate delineation of the left ventricle (LV), especially the interventricular border. In order to obtain magnified cardiac images, a radionuclide gated equilibrium study was performed with a converging (CV) collimator. We compared these two methods in terms of image quality and estimation of LV ejection fraction (EF). Twenty-five children (age, 10 months to 6 years, mean 2.5 years; weight, 5.5 to 20 kg, mean 12 kg) with various heart diseases were studied with administration of 3-7 mCi 99mTc human serum albumin. The GP collimator was used in 15 subjects and the CV collimator in 16. The CV collimator provided optimal magnification and better resolution than the GP type. Cardiac images obtained with the CV collimator facilitated precise delineation of the entire interventricular border in all 16 cases. Those obtained with the GP collimator showed poor delineation of the interventricular border in four subjects. Both GP and CV collimations enabled LVEFs to be calculated, and the values correlated well with those obtained by cine-angiography. The correlation coefficient, however, was higher with the CV collimator (r = 0.787 vs. 0.861, p less than 0.001). Radionuclide cardiac blood-pool study with CV collimator has clinical significance because it provides sufficiently magnified cardiac images with high resolution, enabling accurate estimation of LVEF in infants and young children.

Child↗
PubMed2004

Commentary: Regulated equilibrium between opposite signals: a general paradigm for T cell function?

The co-signaling receptors specific for the different members of the B7 molecular family are cell surface glycoproteins that are essential to modulate and tune the TCR-mediated activation of T lymphocytes. The common characteristic is that their function appears to be dependent on the engagement of TCR by antigenic peptides presented in the MHC context by antigen-presenting cells. Interestingly, co-signaling molecules can be distinguished into costimulators and co-inhibitors, the prototype being represented by CD28 and CTLA-4, respectively. In the case of costimulators, the co-signals integrate the signal originated from the TCR resulting in optimal T cell activation (two-signal model). In the case of co-inhibitors, the co-signals would moderate and/or switch off the Ag-dependent T cell activation, thus acting as negative regulators of immune responses. The growing number of novel co-signaling molecules has recently highlighted the need to integrate the two-signal model with the emerging data on the different co-inhibitory interactions. Thus, a model has been proposed based on the idea that the TCR signal alone cannot take a full decision on the nature of the functional outcome following an antigen-specific stimulation and that this final event is governed by the co-signaling molecules.

Immune System↗