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PubMed2005

Electronic structure study of the initiation routes of the dimethyl sulfide oxidation by OH.

In the present work the potential energy surface (PES) corresponding to the different initiation routes of the oxidation mechanism of DMS by hydroxyl radical in the absence of O(2) has been studied, and connections among the different stationary points have been established. Single-point high level electronic structure calculations at lower level optimized geometries have been shown to be necessary to assure convergence of energy barriers and reaction energies. Our results demonstrate that the oxidation of DMS by OH turns out to be initiated via three channels: a hydrogen abstraction channel that through a saddle point structure finally leads to CH(3)SCH(2) + H(2)O, an addition-elimination channel that firstly leads to an adduct complex (AD) and then via an elimination saddle point structure finally gives CH(3)SOH and CH(3) products, and a third channel that through a concerted pathway leads to CH(3)OH and CH(3)S. The H-abstraction and the addition-elimination channels initiate by a common pathway that goes through the same reactant complex (RC). Our theoretical results agree quite well with the branching ratios experimentally assigned to the formation of the different products. Finally, the calculated equilibrium constants of the formation of the complex AD and the hexadeuterated complex AD from the corresponding reactants, as a function of the temperature, are in good accordance with the experimental values.

Journal Article↗

PubMed1998

DNA binding properties of a chemically synthesized DNA binding domain of hRFX1.

The RFX DNA binding domain (DBD) is a novel highly conserved motif belonging to a large number of dimeric DNA binding proteins which have diverse regulatory functions in eukaryotic organisms, ranging from yeasts to human. To characterize this novel motif, solid phase synthesis of a 76mer polypeptide corresponding to the DBD of human hRFX1 (hRFX1/DBD), a prototypical member of the RFX family, has been optimized to yield large quantities (approximately 90 mg) of pure compound. Preliminary two-dimensional1H NMR experiments suggested the presence of helical regions in this sequence in agreement with previously reported secondary structure predictions. In gel mobility shift assays, this synthetic peptide was shown to bind in a cooperative manner the 23mer duplex oligodeoxynucleotide corresponding to the binding site of hRFX1, with a 2:1 stoichoimetry due to an inverse repeat present in the 23mer. The stoichiometry of this complex was reduced to 1:1 by decreasing the length of the DNA sequence to a 13mer oligonucleotide containing a single half-site. Surface plasmon resonance measurements were achieved using this 5'-biotylinated 13mer oligonucleotide immobilized on an avidin-coated sensor chip. Using this method an association constant (K a = 4 x 10(5)/M/s), a dissociation constant (K d = 6 x 10(-2)/s) and an equilibrium dissociation constant (K D = 153 nM) were determined for binding of hRFX1/DBD to the double-stranded 13mer oligonucleotide. In the presence of hRFX1/DBD the melting temperature of the 13mer DNA was increased by 16 degreesC, illustrating stabilization of the double-stranded conformation induced by the peptide.

Amino Acid Sequence↗

PubMed2006

Quantitative structure-activity relationships (QSARs) within cytochromes P450 2B (CYP2B) subfamily enzymes: the importance of lipophilicity for binding and metabolism.

The results of qualitative structure-activity relationship (QSAR) analysis are reported for several series of compounds which act as substrates for mammalian CYP2B subfamily enzymes, together with a homologous series of aliphatic primary amines which are known to inhibit CYP2B enzymes. It is found that the compound lipophilicity in the form of the log P value (where P is the octanol/water partition coefficient) is related, either linearly or quadratically, to equilibrium constants of inhibition (Ki), binding (Ks) or metabolism (Km) depending on the series of compounds in question. In some instances, the difference between frontier orbital energy levels (deltaE) also features in several of the log P expressions with biological activity. Also present in a small number of correlations are parameters which are likely to be related to logP: namely, Rm, which is the partitioning factor derived from thin layer chromatography (TLC) retention times, and also the compound molecular weight (Mr). All of these three parameters ((log P, Rm and Mr) are thought to be related to the compound's ability to desolvate the P450 active site when they bind to the enzyme. Although the linear relationships between lipophilicity and CYP2B-related activity point to a major role for desolvation of the enzyme binding site in the overall interaction, it is noted that there may be an optimal log P value displayed by preferred substrates as shown by parabolic relationships with this lipophilic parameter. In addition, there is a remarkable similarity in the coefficients for the log P term of any QSAR expression, which suggests that the hydrophobicity of CYP2B active sites may be broadly equivalent between the various mammalian species.

Animals↗

PubMedDate not supplied

[Dinitroorthocresol dissociation of oxidative phosphorylation in the rat liver perfused in situ].

Perfusion of the rat liver in situ for 150 min provides for maintaining optimal values of acid-base balance for the following indexes: surplus of bases, content of standard bicarbonate, buffer bases pH, pO2, pCO2, HbO2, the level of bile secretion, content of lactate, pyruvate, ATP, ADP, that evidences for a high functional activity in the tissue. Introduction of dinitro-ortho-cresol (DNC) into the perfusion liquid causes development of acidosis. DNC results in dissociation of oxidative phosphorylation: the content of ATP and intensity of inorganic phosphorus utilization decrease, oxygen uptake intensifies. A compensatory increase in the glycolysis intensity directed to maintaining the level of macroergs under these conditions is is pronounced in the intensified uptake of glucose, in a rise in the content of lactate in perfusate and an increase in the pyruvate kinase activity in the liver. The redox state of NAD-pairs (ratio of [NAD+] : [NADN] calculated from the content of redox metabolites and the equilibrium constant for the lactate dehydrogenase system shifts toward an increase in the reducing properties of hepatocytes cytoplasm. The phosphate potential value calculated from the ratio [ATP] : [ADP] - [Pinor] lowers under conditions of the experiment.

Acid-Base Equilibrium↗

PubMed2002

Universal solid-phase approach for the immobilization, derivatization, and resin-to-resin transfer reactions of boronic acids.

Boronic acid-containing molecules are employed in a broad range of biological, medicinal, and synthetic applications. These compounds, however, tend to be difficult to handle by solution-phase methods. Herein, this problem is addressed with the development of the first general solid-phase approach for the derivatization of functionalized boronic acids. This approach is based on the use of a diethanolamine resin anchor that facilitates boronic acid immobilization by avoiding the need for exhaustive removal of water in the esterification process. The immobilization of a wide variety of boronic acids onto N,N-diethanolaminomethyl polystyrene (DEAM-PS, 1) can be performed within minutes by simple stirring in anhydrous solvents at room temperature. Evidence for the formation of a bicyclic diethanolamine boronate with putative N-B coordination was shown by (1)H NMR analysis of DEAM-PS-supported p-tolylboronic acid. The hydrolytic cleavage of the same model boronic acid from the DEAM-PS resin was studied by UV spectroscopy. Hydrolysis and attachment were shown to occur under a rapidly attained equilibrium, and a large excess of water (>32 equiv) is required to effect a practically quantitative release of boronic acids from DEAM-PS. Despite their relative sensitivity to water and alcohols, DEAM-PS-bound arylboronic acids functionalized with a formyl, a bromomethyl, a carboxyl, or an amino group can be transformed in good to excellent yields into a wide variety of amines, amides, anilides, and ureas, respectively. Ugi multicomponent reactions on DEAM-PS-supported aminobenzeneboronic acids, derivatization of multifunctional arylboronic acids, and sequential reactions can also be carried out efficiently. These new DEAM-PS-supported arylboronic acids can be employed directly into resin-to-resin transfer reactions (RRTR). This type of multiresin process helps eliminate time-consuming cleavage and transfer operations, thereby considerably simplifying the outlook of combinatorial library synthesis by manual or automated means. This concept was illustrated by a set of optimized procedures for the Suzuki cross-coupling and the borono-Mannich reactions.

Boronic Acids↗

PubMed2005

Investigation of oral bioavailability and brain distribution of the Ind(8)-Val conjugate of indinavir in rodents.

Protease inhibitors are successfully used for the treatment of acquired immune deficiency syndrome (AIDS) although their biopharmaceutical characteristics are not optimal. Prodrugs have therefore been synthesized to increase protease inhibitor bioavailability and brain distribution. Among several compounds tested, a valine derivative of indinavir (Ind(8)-Val) showed promising characteristics using an in-vitro Caco-2 cell model. The objective of this study was to further investigate this compound using in-situ and in-vivo approaches. The pharmacokinetics of indinavir (Ind) and Ind(8)-Val were investigated in rats after intravenous and oral administration. Free indinavir resulting from in-vivo hydrolysis of Ind(8)-Val could not be detected in the plasma of rats receiving Ind(8)-Val. Furthermore Ind(8)-Val bioavailability was only 32% on average compared with 76% for indinavir, and effective permeability coefficients determined with a single-pass intestinal perfusion method were close to 25x10(6)cms(-1) for the two compounds. Brain-to-plasma concentration ratios in the post equilibrium phase after intravenous administration to mice were 9.7+/-8.1% for indinavir and 2.5+/-2.7% for Ind(8)-Val. In conclusion, the promising biopharmaceutical characteristics of Ind(8)-Val suggested from previous in-vitro experiments with the Caco-2 cell model were not confirmed by in-situ and in-vivo experiments.

Administration, Oral↗

PubMed1998

Molecular properties of ClpAP protease of Escherichia coli: ATP-dependent association of ClpA and clpP.

The ClpAP protease from Escherichia coli consists of the ATP-binding regulatory component, ClpA (subunit Mr 84 165), and the proteolytic component, ClpP (subunit Mr 21 563). Our hydrodynamic studies demonstrate that the predominant forms of these proteins in solution correspond to those observed by electron microscopy. ClpP and proClpP(SA), which in electron micrographs appear to have subunits arranged in rings of seven subunits, were found by ultracentrifugation to have s20,w values of 12.2 and 13.2 S and molecular weights of 300 000 and 324 000 +/- 3000, respectively, indicating that the native form of each consists of two such rings. The two intact rings of ClpP were separated in the presence of >/= 0.1 M sulfate at low temperatures, suggesting that ring-ring contacts are polar in nature and more easily disrupted than subunit contacts within individual rings. Sedimentation equilibrium analysis indicated that ClpA purified without nucleotide exists as an equilibrium mixture of monomers and dimers with Ka = (1.0 +/- 0.2) x 10(5) M-1 and that, upon addition of MgATP or adenosine 5'-O-(3-thiotriphosphate), ClpA subunits associated to a form with Mr 505 000 +/- 5000, consistent with the hexameric structure seen by electron microscopy. Sedimentation velocity and gel-filtration analysis showed that the nucleotide-promoted hexamer of ClpA (s20,w = 17.2 S) binds tightly to ClpP producing species with s20,w values of 21 and 27 S (f/f0 = 1.5 and 1.8, respectively), consistent with electron micrographs of ClpAP that show a single tetradecamer of ClpP associated with either one or two ClpA hexamers [Kessel et al. (1995) J. Mol. Biol. 250, 587-594]. Under assay conditions in the presence of ATP and Mg2+, the apparent dissociation constant of hexameric ClpA and tetradecameric ClpP was approximately 4 +/- 2 nM. By the method of continuous variation, the optimal ratio of ClpA to ClpP in the active complex was 2:1. The specific activities of limiting ClpA and ClpP determined in the presence of an excess of the other component indicated that the second molecule of ClpA provides very little additional activation of ClpP.

Adenosine Triphosphatases↗

PubMed1984

Development of a non-extracted 'two-site' immunoradiometric assay for corticotropin utilizing extreme amino- and carboxy-terminally directed antibodies.

The development of a 'two-site' immunoradiometric assay (i.r.m.a.) for the direct estimation of human corticotropin-(1-39)-peptide in plasma is described. The assay is based on the simultaneous addition of 125I-labelled sheep anti-(N-terminal corticotropin) IgG (immunoglobulin G) antibodies and rabbit anti-(C-terminal corticotropin) antiserum to standards and unknowns (0.5 ml) followed by 18h incubation. The use of solid-phase reagents was avoided in order to minimize non-specific effects and the time required for reactants to reach equilibrium. Instead, the separation of corticotropin-bound from free labelled antibody is achieved by the addition of sheep anti-(rabbit IgG) antiserum, which precipitates bound labelled antibody by complex-formation with rabbit anti-corticotropin antibodies, which are also hormone-bound. Several 125I-labelled sheep anti-(N-terminal corticotropin) IgG preparations were assessed in the i.r.m.a. Although each was derived from antisera raised to a thyroglobulin conjugate of synthetic corticotropin-(1-24)-peptide (Synacthen), purification of immunoglobulins before iodination by selective immunoadsorption resulted in preparations with distinct specificities which demonstrated marked differences in binding to intact human corticotropin-(1-39)-peptide. These preparations are compared in combination with two rabbit anti-(C-terminal corticotropin) antisera. A 'two-site' assay based on the use of 125I-labelled sheep anti-[ corticotropin-(2-16)-peptide] IgG and rabbit anti-[corticotropin-(34-39)-peptide] antiserum was optimized, since steric inhibition of antibody binding was avoided with this combination and because the measurement of only intact human corticotropin-(1-39)-peptide and not fragments was assured by the use of terminal antibodies. This i.r.m.a. is characterized by rapid equilibration of reactants, a wide 'operating range' (the precision of dose estimates was less than 4% over the range 30-2200 pg/ml) and high sensitivity [8 pg of corticotropin/ml (95% confidence interval 3.7-12.0) (4 pg minimal detectable mass) can be detected directly in plasma].

Adrenocorticotropic Hormone↗

PubMed1988

Insulin effect on GABA uptake in astroglial primary cultures.

Astroglial cultures from newborn mouse cerebral cortex contain [125I]Insulin binding sites. Binding was specific, reversible, time dependent and reached equilibrium after 45 min. Insulin analogues compete for this [125I]Insulin binding. Incubation of cerebral cortex astroglial cultures with insulin induced a time- and dose-dependent inhibition of the [3H]GABA high affinity uptake. A decrease in the Vmax rather than an effect on the Km was observed. This effect was dose-dependent and effective at 10(-10) M. Autoradiographic observations on the cell monolayer showed the presence of two groups of cells: one which strongly takes up [3H]GABA and consist in smaller GFAP positive process-bearing cells and another group of much flatter and larger GFAP positive cells which uptake was lower. The smaller stellate cells were apparently the most sensitive to insulin effect. These results: 1) confirm the presence of insulin binding sites on astroglial primary cultures, 2) show an effect of insulin on [3H]GABA high affinity uptake of these cells; this effect being optimal on a stellate-like population of astrocytes, and 3) indicate that insulin may interfere in neuromodulation through astroglial signals.

Animals↗

PubMed1981

Hexose transport in human adipocytes: factors influencing the response to insulin and kinetics of methylglucose and glucose transport.

Optimal experimental conditions were defined for measuring the initial uptake rate of the non-metabolizable sugar analogue 3-O-methylglucose in non-stimulated and insulin-stimulated human adipocytes. The permeability of the adipocyte plasma membrane for tracer methylglucose (100 mumol/l) was 2.9 X 10(-7) cm X s-1 at 37 degrees C and slightly lower at 20 degrees C. At 37 degrees C and pH 7.4 insulin (5 nmol/l) increased the permeability about twofold (range 1.5 to fivefold) with half maximal effect at about 100 pmol/l). At pH 7.0 the dose response curve for the insulin effect on the uptake rate of methylglucose was shifted about 2.5-fold to the right. The permeability to L-glucose due to simple diffusion was estimated as 3.0 X 10(-10) cm X s-1 suggesting that uptake of methylglucose occurs almost exclusively by facilitated diffusion. The Km for methylglucose equilibrium exchange in insulin stimulated cells was about 4.8 mmol/l. The initial uptake of tracer methylglucose in insulin-stimulated cells was inhibited by unlabelled methylglucose and by D-glucose with inhibition constants of about 3.8 and 7.7 mmol/l respectively. Uptake of tracer 2-deoxyglucose (50 mumol/l) in insulin-stimulated adipocytes was linear from 10 s to 5 min whereas the rate of uptake in the presence of 3 mmol/l of D-glucose was markedly decreased suggesting that deoxyglucose uptake after a few minutes is mainly limited by hexokinase in the presence of glucose.

Adipose Tissue↗

PubMed1985

A method of estimating from two aligned present-day DNA sequences their ancestral composition and subsequent rates of substitution, possibly different in the two lineages, corrected for multiple and parallel substitutions at the same site.

The course of evolutionary change in DNA sequences has been modeled as a Markov process. The Markov process was represented by discrete time matrix methods. The parameters of the Markov transition matrices were estimated by least-squares direct-search optimization of the fit of the calculated divergence matrix to that observed for two aligned sequences. The Markov process corrected for multiple and parallel substitutions of bases at the same site. The method avoided the incorrect assumption of all previously described methods that the divergence between two present-day sequences is twice the divergence of either from the common and unknown ancestral sequence. The three previous methods were shown to be equivalent. The present method also avoided the undesirable assumptions that sequence composition has not changed with time and that the substitution rates in the two descendant lineages were the same. It permitted simultaneous estimation of ancestral sequence composition and, if applicable, of different substitution rates for the two descendant lineages, provided the total number of estimated parameters was less than 16. Properties of the Markov chain were discussed. It was proved for symmetric substitution matrices that all elements of the equilibrium divergence matrix equal 1/16, and that the total difference in the divergence matrix at epoch k equals the total change in the common substitution matrix at epoch 2k for all values of k. It was shown how to resolve an ambiguity in the assignment of two different substitution rates to the two descendant lineages when four or more similar sequences are available. The method was applied to the divergence matrix for codon site 3 for the mouse and rabbit beta-globins. This observed divergence matrix was significantly asymmetric and required at least two different substitution rates. This result could be achieved only by using different asymmetric substitution matrices for the two lineages.

Animals↗

PubMed1993

Europium-labelled recombinant protein G. A fast and sensitive universal immunoreagent for time-resolved immunofluorometry.

Recombinant protein G was labelled with europium by conjugating the protein with Eu3+ chelate of a p-isothiocyanatobenzyl derivative of diethylenetriaminetetraacetic acid, a bifunctional chelating agent specifically optimized for labelling of immunoreagents with lanthanide ions. The labelling produced a universal reagent for time-resolved fluorometric immunoassays based on the principle of dissociative fluorescence enhancement (DELFIA). The optimum labelling level of about eight chelates per protein yielded a highly sensitive and stable reagent which retained its affinity for IgG and exhibited low non-specific binding to coated solid surfaces. The reagent was evaluated in an immunoassay of anti-tetanus antibodies in human serum samples and the results were compared to those obtained with Eu-labelled polyclonal and Eu-labelled monoclonal anti-human IgG antibodies. The detection limit of the assay was 0.003 mU/ml (0.3 microU per assay well). After a 100-fold dilution of the samples, the assay range extended from 0.3 mU/ml to 100,000 mU/ml with a linear range of five log orders. The incubation with Eu-labelled protein G reached equilibrium after a 15 min incubation. The rapid kinetics, the low non-specific background and the high specific binding suggest that Eu-protein G can serve as a universal label for immunoassays based on IgG binding to solid surfaces.

Antibodies, Bacterial↗

PubMed2002

Column selectivity from the perspective of the solvation parameter model.

The solvation parameter model is a useful tool for delineating the contribution of defined intermolecular interactions to retention of neutral molecules in separation systems based on a solute equilibrium between a gas, liquid or fluid mobile phase and a liquid or solid stationary phase. The free energy for this process is decomposed into contributions for cavity formation and the set up of intermolecular interactions identified as dispersion, electron lone pair, dipole-type and hydrogen bonding. The relative contribution of these interactions is indicated by a series of system constants determined by the difference of the defined interaction in the two phases. The interpretation of these system constants as a function of experimental factors that affect retention in the chromatographic system provides the connection between relative retention (selectivity) and the control variables for the separation system. To aid in the understanding of these processes we perform an analysis of system constants for gas chromatography, liquid chromatography, supercritical fluid chromatography and micellar electrokinetic chromatography as a function of different experimental variables as a step towards gaining a theoretical understanding of selectivity optimization for method development.

Chromatography, Gas↗

PubMed2004

Calculation of 19F and 27Al NMR parameters for rosenbergite, AlF[F0.5(H2O)0.5]4.H2O, a possible model for Al hydroxyfluorides in solution.

(19)F and (27)Al NMR chemical shifts are calculated for the F and Al atoms of the mineral rosenbergite, AlF[F(0.5)(H(2)O)(0.5)](4).H(2)O The structure of rosenbergite consists of infinite chains of F-corner-sharing Al[F(4)(H(2)O)(2)] octahedra and isolated water molecules. An F-centered molecular cluster of composition Al(2)F(3)(OH(2))(8) (3+) was initially used to model the mineral, with geometries taken both from the two different available x-ray crystal structures and from equilibrium geometries calculated at the 6-31G* B3LYP level (both with and without polarizable continuum solvation). Related Al(F)F(n) em leader clusters, with additional F(-) replacing H(2)O, were also studied. A larger Al-centered cluster model Al(3)F(4)(OH(2))(12) (5+) was also generated from one of the x-ray geometries and produced very similar bridging F shieldings but slightly different Al shieldings. The NMR shieldings were calculated using both HF and B3LYP GIAO methods, with 6-311+G(2df,p) basis sets, and the HF and B3LYP results averaged for the F shieldings as described in previous work. Calculated (19)F NMR shifts (relative to CCl(3)F) using this procedure were within a few ppm of experiment when either set of x-ray crystal structure coordinates was used, but differed by as much as 20 ppm for the energy-optimized geometries. Rosenbergite-like fragments with geometries optimized in water, simulated by a PCM, were used to model Al hydroxyfluoride species in solution. The (19)F NMR shifts for the bridging F atoms in several such model complexes are very similar to those usually attributed to monomeric species such as Al(OH(2))(5)F(2+) in solution, suggesting that the solution species are actually corner bridging oligomers. The F in the monomeric Al(OH(2))(5)F(2+) solution species is too strongly shielded by about 20 ppm to match the experimental peak usually assigned to it.

Journal Article↗

PubMed2006

A rigorous multiple independent binding site model for determining cell-based equilibrium dissociation constants.

A new 4-parameter nonlinear equation based on the standard multiple independent binding site model (MIBS) is presented for fitting cell-based ligand titration data in order to calculate the ligand/cell receptor equilibrium dissociation constant and the number of receptors/cell. The most commonly used linear (Scatchard Plot) or nonlinear 2-parameter model (a single binding site model found in commercial programs like Prism(R)) used for analysis of ligand/receptor binding data assumes only the K(D) influences the shape of the titration curve. We demonstrate using simulated data sets that, depending upon the cell surface receptor expression level, the number of cells titrated, and the magnitude of the K(D) being measured, this assumption of always being under K(D)-controlled conditions can be erroneous and can lead to unreliable estimates for the binding parameters. We also compare and contrast the fitting of simulated data sets to the commonly used cell-based binding equation versus our more rigorous 4-parameter nonlinear MIBS model. It is shown through these simulations that the new 4-parameter MIBS model, when used for cell-based titrations under optimal conditions, yields highly accurate estimates of all binding parameters and hence should be the preferred model to fit cell-based experimental nonlinear titration data.

Algorithms↗

PubMed2005

The pre-vaccination regional epidemiological landscape of measles in Italy: contact patterns, effort needed for eradication, and comparison with other regions of Europe.

BACKGROUND: Strong regional heterogeneity and generally sub-optimal rates of measles vaccination in Italy have, to date, hampered attainment of WHO targets for measles elimination, and have generated the need for the new Italian National Measles Elimination Plan. Crucial to success of the plan is the identification of intervention priorities based upon a clear picture of the regional epidemiology of measles derived from the use of data to estimate basic parameters. Previous estimates of measles force of infection for Italy have appeared anomalously low. It has been argued elsewhere that this results from Italian selective under-reporting by age of cases and that the true measles force of infection in Italy is probably similar to that of other European countries. A deeper examination of the evidence for this conjecture is undertaken in the present paper. METHODS: Using monthly regional case notifications data from 1949 to the start of vaccination in 1976 and notifications by age from 1971-76, summary equilibrium parameters (force of infection (FOI), basic reproductive ratio (R0) and critical vaccination coverage (pc)) are calculated for each region and for each of 5 plausible contact patterns. An analysis of the spectra of incidence profiles is also carried out. Finally a transmission dynamics model is employed to explore the correspondence between projections using different estimates of force of infection and data on seroprevalence in Italy. RESULTS: FOI estimates are lower than comparable European FOIs and there is substantial regional heterogeneity in basic reproductive ratios; certain patterns of contact matrices are demonstrated to be unfeasible. Most regions show evidence of 3-year epidemic cycles or longer, and compared with England & Wales there appears to be little synchronisation between regions. Modelling results suggest that the lower FOI estimated from corrected aggregate national data matches serological data more closely than that estimated from typical European data. CONCLUSION: Results suggest forces of infection in Italy, though everywhere remaining below the typical European level, are historically higher in the South where currently vaccination coverage is lowest. There appears to be little evidence to support the suggestion that a higher true force of infection is masked by age bias in reporting.

Journal Article↗

PubMed1984

Identification of the Raji cell membrane-derived C1q inhibitor as a receptor for human C1q. Purification and immunochemical characterization.

We have shown previously that an activity which is capable of precipitating purified C1q and inhibiting some of the C1q-dependent biologic reactions could be solubilized from the membranes of both normal human peripheral B lymphocytes and a B cell-derived lymphoblastoid cell line (Raji), both of which are known to possess receptors for human C1q. In this report we present evidence that this membrane-associated C1q inhibitor is a chondroitinase-insensitive macromolecule and is the receptor for human C1q. The receptor was solubilized from membranes of Raji cells with Nonidet P-40 and purified to homogeneity using C1q-Sepharose 4B affinity chromatography. Equilibrium density gradient centrifugation analysis revealed that the complex could be resolved into a protein-rich, low density fraction and a carbohydrate-rich, high density fraction. The large hydrodynamic size, coupled with the high buoyant density, suggests that a proteoglycan is a constituent of the complex and indicates that the receptor might be a macromolecular complex of a proteoglycan portion noncovalently linked to a 60-70 kD glycoprotein. The glycoprotein moiety, in turn, consists of two or more identical (70,000 mol wt) polypeptide chains held together by disulfide bonds and constitutes the C1q receptor (C1qR). Sucrose density ultracentrifugation analysis showed that the isolated receptor sediments with an apparent rate of 4.2 S. Immunochemical analyses demonstrated that a typical preparation of the C1qR complex consists of approximately 23% uronic acid and approximately 21% galactosamine with a galactosamine-to-glucosamine ratio of 3.2. Binding of C1q to the receptor was found to be optimal at low ionic strength and neutral or near-neutral pH (7-7.4). The isolated receptor was found to inhibit C1q hemolytic function, abrogate C1q-dependent rosette formation, and block the C1q-dependent, cell-mediated cytotoxicity, all of which are activities mediated by the receptor.

Amino Acids↗

PubMedDate not supplied

Gas-partitioning tracer test to quantify trapped gas during recharge.

Dissolved helium and bromide tracers were used to evaluate trapped gas during an infiltration pond experiment. Dissolved helium preferentially partitioned into trapped gas bubbles, or other pore air, because of its low solubility in water. This produced observed helium retardation factors of as much as 12 relative to bromide. Numerical simulations of helium breakthrough with both equilibrium and kinetically limited advection/dispersion/retardation did not match observed helium concentrations. However, better fits were obtained by including a decay term representing the diffusive loss of helium through interconnected, gas-filled pores. Calculations indicate that 7% to more than 26% of the porosity beneath the pond was filled with gas. Measurements of laboratory hydraulic properties indicate that a 10% decrease in saturation would reduce the hydraulic conductivity by at least one order of magnitude in the well-sorted sandstone, but less in the overlying soils. This is consistent with in situ measurements during the experiment, which show steeper hydraulic gradients in sandstone than in soil. Intrinsic permeability of the soil doubled during the first six months of the experiment, likely caused by a combination of dissolution and thermal contraction of trapped gas. Managers of artificial recharge basins may consider minimizing the amount of trapped gas by using wet, rather than dry, tilling to optimize infiltration rates, particularly in well-sorted porous media in which reintroduced trapped gas may cause substantial reductions in permeability. Trapped gas may also inhibit the amount of focused infiltration that occurs naturally during ephemeral flood events along washes and playas.

Bromides↗