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C F Anderson

Publications and source records attributed to C F Anderson.

At least 19 recordsLinked to original sources
PubMed1996

Thermodynamic characterization of interactions of native bovine serum albumin with highly excluded (glycine betaine) and moderately accumulated (urea) solutes by a novel application of vapor pressure osmometry.

The thermodynamic consequences of interactions of native bovine serum albumin (BSA) with two smaller solutes (glycine betaine or urea) in aqueous solution are characterized by a novel application of vapor pressure osmometry (VPO), which demonstrates the utility of this method of investigating preferential interactions involving solutes that are either accumulated or excluded near the surface of a protein. From VPO measurements of osmolality (water activity) as a function of the solute concentration in the presence and absence of BSA, we determine the dependence of the solute molarity (C3) on that of BSA (C2) at fixed temperature (37 degrees C), pressure (approximately 1 atm), and osmolality (over the range 0-1.6 molal). After some thermodynamic transformations, these results yield values of [formula: see text] which characterizes the interdependence of solute molalities when temperature, pressure, and the chemical potential of solute 3 are fixed. This form of the preferential interaction coefficient can be interpreted directly in terms of the molecular exclusion or accumulation of the solute (relative to water) near the protein surface. Within experimental uncertainty, [formula: see text] is proportional to m3 both for glycine betaine (0-0.9 m) and for urea (0-1.6 m). For glycine betaine [formula: see text] = -49 +/- 4, a value consistent with the interpretation that this solute is completely excluded from the hydrated surface of BSA, whereas for urea [formula: see text] = 6 +/- 1, which indicates a moderate extent of accumulation at the surface of native BSA. The preferential accumulation of solutes (e.g., urea) that have some binding affinity for a protein can be quantified and interpreted using the two-domain model if the extent of hydration of the protein has been determined using a completely excluded solute (e.g., glycine betaine). Complete exclusion from the local hydration domain surrounding proteins, if general, justifies the use of glycine betaine as a thermodynamic probe of the changes in hydration that accompany protein folding, protein association, and protein-ligand binding interactions.

Betaine↗
PubMed1996

Compensating effects of opposing changes in putrescine (2+) and K+ concentrations on lac repressor-lac operator binding: in vitro thermodynamic analysis and in vivo relevance.

Ion concentrations (K+, Glu-) in the cytoplasm of growing Escherichia coli cells increase strongly with increases in the osmolarity of a defined growth medium. While in vitro experiments demonstrate that the extent of protein-nucleic acid interactions (PNAI) depends critically on salt concentration, in vivo measurements indicate that cells maintain a relatively constant extent of PNAI independent of the osmolarity of growth. How do cells buffer PNAI against changes in the cytoplasmic environment? At high osmolarity, the increase in macromolecular crowding which accompanies the reduction in amount of cytoplasmic water in growing cells appears quantitatively sufficient to compensate for the increase in [K+]. At low osmolarity, however, changes in crowding appear to be insufficient to compensate for changes in [K+], and additional mechanisms must be involved. Here we report quantitative determinations of in vivo total concentrations of polyamines (putrescine(2+), spermidine(3+)) as a function of osmolarity (OsM) of growth, and in vitro binding data on the effects of putrescine concentration on a specific PNAI (lac repressor-lac operator) as a function of [K+]. The total concentration of putrescine in cytoplasmic water decreases at least eightfold from low osmolarity (approximately 64 mmol (l H2O)-1 at 0.03 OsM) to high osmolarity (approximately 8 mmol (l H2O)-1 at 1.02 OsM). Over this osmotic range the total [K+] increases from approximately 0.2 mol (l H2O)-1 to approximately 0.8 mol (lH2O)-1. We find that the effect of putrescine concentration on the repressor-operator interaction in vitro is purely competitive and is quantitatively described by a simple competition formalism in which lac repressor behaves a a specific-binding oligocation (ZR = 8+/-3). We demonstrate that this thermodynamic result is consistent with a structural analysis of the number of positively charged side-chains on two DNA binding domains of repressor which interact with the phosphodiester backbone of the operator site. Since this oligocation character of the binding surface of DNA-binding proteins appears to be general, we propose the competitive effects of putrescine and K+ concentrations on the strength of specific binding are general. At low osmolarity, compensating changes in putrescine and K+ concentration in response to changes in external osmolarity provide a general mechanism for E. coli to vary cytoplasmic osmolarity while maintaining a constant extent of PNAI.

Base Sequence↗
PubMed1996

Large electrostatic differences in the binding thermodynamics of a cationic peptide to oligomeric and polymeric DNA.

Results presented here demonstrate that the thermodynamics of oligocation binding to polymeric and oligomeric DNA are not equivalent because of long-range electrostatic effects. At physiological cation concentrations (0.1-0.3 M) the binding of an oligolysine octacation KWK6-NH2 (+8 charge) to single-stranded poly(dT) is much stronger per site and significantly more salt concentration dependent than the binding of the same ligand to an oligonucleotide, dT(pdT)10 (-10 charge). These large differences are consistent with Poisson-Boltzmann calculations for a model that characterizes the charge distributions with key preaveraged structural parameters. Therefore, both the experimental and the theoretical results presented here show that the polyelectrolyte character of a polymeric nucleic acid makes a large contribution to both the magnitude and the salt concentration dependence of its binding interactions with simple oligocationic ligands.

Cations↗
PubMed1996

Umbilical venous Doppler velocity pulsations and inferior vena cava pressure elevations in fetal lambs.

OBJECTIVE: To examine effects of fluid administration on inferior vena cava pressure and umbilical venous Doppler velocities in the term fetal lamb. METHODS: With the ewe given inhalation anesthetics, eight chronically instrumented intrauterine fetal lambs at 125-135 days' gestation were given normal saline fluid boluses. Inferior vena cava peak pressures and umbilical venous Doppler velocities were measured before, during, and after administration of normal saline. Pressures were obtained with fluid-filled and solid state pressure transducers. RESULTS: Umbilical venous Doppler velocity pulsations developed in six fetuses after 120 mL and all eight fetuses after 240 mL of fluid were administered. Inferior vena cava peak pressure increased from 5.15 +/- 2.7 to 10.9 +/- 3.9 mmHg (P < .001). Heart rate did not change significantly, and umbilical arterial systolic-to-diastolic velocity ratios decreased (P < .03). CONCLUSION: Umbilical venous Doppler velocity pulsations developed after fluid administration and were associated with increases in inferior vena cava peak pressure. These findings suggest that umbilical venous pulsations develop when fetal venous pressures are elevated.

Animals↗
PubMed1996

Application of A.S.P.E.N. clinical guidelines: parenteral nutrition use at a university hospital and development of a practice guideline algorithm.

Few studies have attempted to implement the 1993 A.S.P.E.N. Guidelines into clinical practice. We retrospectively studied parenteral nutrition (PN) use over a 3-month period in 148 patients. Forty-three percent of PN starts lasted < or = 5 days. This short-term use of PN was more likely to occur when peripheral access for PN was used. Overall, short-term use of PN was found over a wide variety of diagnoses for a large number of reasons given in the medical record. Next, an algorithm was developed for the decision to initiate PN based on the 1993 A.S.P.E.N. Guidelines and was used to evaluate the use of PN. Several potential means for reducing overuse of PN were identified: using established criteria for malnutrition, restricting PN to known conditions in which the gastrointestinal (GI) tract cannot be used, and recognizing the transitory nature of many GI disorders.

Algorithms↗
PubMed1995

K(+)-ribosome interactions determine the large enhancements of 39K NMR transverse relaxation rates in the cytoplasm of Escherichia coli K-12.

As a probe of physical chemical properties of the intracellular environment, we measured 39K NMR transverse relaxation rates in concentrated cell slurries of Escherichia coli K-12 grown in minimal medium over a range of osmolarities (from 0.1 to 1.0 OsM) and after plasmolysis. The 39K transverse relaxation at a resonance frequency of approximately 18.67 MHz is biexponential under all conditions, and 100% of the expected signal intensity is detected. Both components of the 39K NMR transverse relaxation are very fast, and the difference between the fast and slow relaxation rates is very large compared to previous measurements on 23Na and 39K in protein and nucleic acid solutions in vitro. The 39K transverse relaxation rates decrease as the osmolarity of the growth media increases but increase dramatically when cells grown in 0.1 OsM media are plasmolyzed at 1.0 OsM. The homogeneous nature and the 100% visibility of the 39K signal indicate the existence of fast exchange among the multiple, magnetically distinguishable populations of 39K which probably exist in the cytoplasm. The absence of static quadrupolar splitting of the cytoplasmic 39K signal (as indicated by a single peak in the spectrum) indicates that the cytoplasm, as probed by 39K NMR, behaves like a concentrated but isotropic nucleic acid solution rather than an anisotropic nucleic acid liquid crystal. To understand the origins of the striking NMR relaxation behavior of 39K in viable cells, we have investigated NMR transverse relaxation rates of 39K (and also 23Na and 35Cl) in E. coli 50S and 70S ribosome solutions in vitro. At concentrations of ions and of ribosomes that to the extent possible mimic those of the cytoplasm of E. coli, we find that 39K, 23Na, and 35Cl transverse relaxation rates all exhibit biexponential behavior, and 39K and 23Na exhibit the large magnitudes and the large difference between the slow and the fast relaxation rates observed in viable cells. These polyanionic ribosome solutions are the only in vitro model system discovered to date that exhibits 39K transverse relaxation rates comparable to those in viable cells. We conclude that K(+)-ribosome interactions are the dominant source of the NMR properties of K+ in E. coli.(ABSTRACT TRUNCATED AT 400 WORDS)

Cytoplasm↗
PubMed1995

Grand canonical Monte Carlo molecular and thermodynamic predictions of ion effects on binding of an oligocation (L8+) to the center of DNA oligomers.

Grand canonical Monte Carlo (GCMC) simulations are reported for aqueous solutions containing excess univalent salt (activities a +/- = 1.76-12.3 mM) and one of the following species: an octacationic rod-like ligand, L8+; a B-DNA oligomer with N phosphate charges (8 < or = N < or = 100); or a complex resulting from the binding of L8+ at the center of an N-mer (24 < or = N < or = 250). Simplified models of these multiply charged species are used in the GCMC simulations to predict the fundamental coulombic contributions to the following experimentally relevant properties: 1) the axial distance over which ligand binding affects local counterion concentrations at the surface of the N-mer; 2) the dependence on N of GCMC preferential interaction coefficients, gamma 32MC identical to delta C3/delta C2l a +/-, T, where C3 and C2 are, respectively, the molar concentrations of salt and the multiply charged species (ligand, N-mer or complex); and 3) the dependence on N of SaKobs identical to d in Kobs/d in a +/- = delta (magnitude of ZJ + 2 gamma 32J), where Kobs is the equilibrium concentration quotient for the binding of L8+ to the center of an N-mer and delta denotes the stoichiometric combination of terms, each of which pertains to a reactant or product J having magnitude of ZJ charges. The participation of electrolyte ions in the ligand binding interaction is quantified by the magnitude of SaKobs, which reflects the net (stoichiometrically weighted) difference in the extent of thermodynamic binding of salt ions to the products and reactants. Results obtained here from GCMC simulations yield a picture of the salient molecular consequences of binding a cationic ligand, as well as thermodynamic predictions whose applicability can be tested experimentally. Formation of the central complex is predicted to cause a dramatic reduction in the surface counterion (e.g., Na+) concentration over a region including but extending well beyond the location of the ligand binding site. For binding a cationic ligand, SaKobs is predicted to be negative, indicating net electrolyte ion release in the binding process. At small enough N, -SaKobs is predicted to decrease strongly toward zero with decreasing N. At intermediate N, -SaKobs appears to exceed its limiting value as N-->infinity.

Cations↗
PubMed1995

Interpretation of preferential interaction coefficients of nonelectrolytes and of electrolyte ions in terms of a two-domain model.

For a three-component system consisting of solvent (1), polymer or polyelectrolyte (2J), and a nonelectrolyte or electrolyte solute (3), a two-domain description is developed to describe thermodynamic effects of interactions between solute components (2J) and (3). Equilibrium dialysis, which for an electrolyte solute produces the Donnan distribution of ions across a semipermeable membrane, provides a fundamental basis for this two-domain description whose applicability is not restricted, however, to systems where dialysis equilibrium is established. Explicit expressions are obtained for the solute-polymer preferential interaction coefficient gamma 3,2J (nonelectrolyte case) and for gamma +,2J and gamma -,2J, which are corresponding coefficients defined for single (univalent) cations and anions, respectively: gamma +,2J = magnitude of ZJ + gamma -,2J = 0.5(magnitude of ZJ + B-,2J + B+,2J) - B1,2Jm3/m1 Here B+,2J, B-,2J, and B1,2J are defined per mole of species J, respectively, as the number of moles of cation, anion, and water included within the local domains that surround isolated molecules of J; ZJ is the charge on J; m3 is the molal concentration of uniunivalent electrolyte, and m1 = 55.5 mol/kg for water. Incorporating this result into a general thermodynamic description(derived by us elsewhere) of the effects of the activity a+ of excess uniunivalent salt on an equilibrium involving two or more charged species J (each of which is dilute in comparison with the salt) yields:SaKobs bS/d a+ A(r+2J r 2j) A(B+2J B-2 2B12Jm3/m1)where KObS is an equilibrium quotient defined in terms of the molar concentrations of the participants, J, and A denotes astoichio metrically weighted combination of terms pertaining to the reactant(s) and product(s). The derivation presented here does not depend on any particular molecular model for salt-polyelectrolyte (or solute-polymer) interactions; it therefore generalizes our earlier (1978) derivation.

Biophysical Phenomena↗
PubMed1995

Analyses of thermodynamic data for concentrated hemoglobin solutions using scaled particle theory: implications for a simple two-state model of water in thermodynamic analyses of crowding in vitro and in vivo.

Quantitative description of the thermodynamic consequences of macromolecular crowding (excluded volume nonideality) is an important component of analyses of the thermodynamics and kinetics of noncovalent interactions of biopolymers in vivo and in concentrated polymer solutions in vitro. By analyzing previously published thermodynamic data, we have investigated extensively the comparative applicability of two forms of scaled particle theory (SPT). In both forms, macromolecules are treated as hard spheres, but MSPT, introduced by Ross and Minton, treats the solvent as a structureless continuum, whereas bulk water molecules are included explicitly as hard spheres in BSPT, an approach developed by Berg. Here we use both MSPT and BSPT to calculate the excluded volume component of the macromolecular activity coefficient of hemoglobin (Hb) at concentrations up to 509 mg/ml by fitting osmotic pressure data for Hb and sedimentation equilibrium data for Hb and sickle-cell Hb (HbS). Both forms of SPT also are used here to analyze the effects of other globular proteins (BSA and Hb) on the solubility of HbS. In applying MSPT and BSPT to analyze macromolecular crowding, the extent of hydration delta Hb (in gH2O/gprotein) is introduced as an adjustable parameter to specify the effective (hard sphere) radius of hydrated Hb. In our nonlinear least-squares fittings based on BSPT, the hard sphere radius of bulk water molecules is either fixed at 1.375 A or floated. Although both forms of SPT yield good fittings (with different values of delta Hb) at Hb concentrations up to 350 mg/ml, only BSPT gives good fittings of all available Hb osmotic pressure data as well as of the sedimentation equilibrium and solubility data. Only BSPT predicts values for delta Hb (approximately 0.5-0.6 g/g) in the range obtained for Hb from hydrodynamic measurements (approximately 0.36-0.78 g/g). These findings indicate the applicability, at least in the context of BSPT, of a simple two-state classification of water (bulk water and water of macromolecular hydration) as a basis for interpreting excluded volume nonideality in concentrated solutions of globular proteins.

Biophysical Phenomena↗
PubMed1995

Importance of coulombic end effects on cation accumulation near oligoelectrolyte B-DNA: a demonstration using 23Na NMR.

The local cation concentration at the surface of oligomeric or polymeric B-DNA is expected, on the basis of MC simulations (Olmsted, M. C., C. F. Anderson, and M. T. Record, Jr. 1989. Proc. Natl. Acad. Sci. USA. 86:7766-7770), to decrease sharply as either end of the molecule is approached. In this paper we report 23Na NMR measurements indicating the importance of this "coulombic" end effect on the average extent of association of Na+ with oligomeric duplex DNA. In solutions containing either 20-bp synthetic DNA or 160-bp mononucleosomal calf thymus DNA at phosphate monomer concentrations [P] of 4-10 mM, measurements were made over the range of ratios 1 < or = [Na]/[LP] < or = 20, corresponding to Na+ concentrations of 4-200 nM. The longitudinal 23Na NMR relaxation rates measured in these NaDNA solutions, Robs, are interpreted as population-weighted averages of contributions from "bound" (RB) and "free" (RF) 23Na relaxation rates. The observed enhancements of Robs indicate that RB significantly exceeds RF, which is approximately equal to the 23Na relaxation rate in an aqueous solution containing only NaCl. Under salt-fre-tconditions ([Na]/[P] = 1), where the enhancement in Robs is maximal, we find that Robs--RF in the solution containing 160-bp DNA is approximately 1.8 times that observed for the 20-bp DNA. For the 160-bp oligomer (which theoretical calculations predict to be effectively polyion-like), we find that a plot of Robs v. [P]/[Na] is linear, as observed previously for sonicated (approximately 700 bp) DNA samples. For the 20-bp oligonucleotide this plot exhibits a marked departure from linearity that can be fitted to a quadratic function of [P]/[Na]. Monte Carlo simulations based on a simplified model are capable of reproducing the qualitative trends in the 23Na NMR measurements analyzed here. In particular, the dependences of Robs--RF on DNA charge magnitude of Z(320 vs. 38 phosphates) and (for the 20-bp oligomer) on [Na]/[P] are well correlated with the calculated average surface concentration of Na+. Thus, effects of sodium concentration on RB appear to be of secondary importance. We conclude that 23Na NMR relaxation measurements are a sensitive probe of the effects of oligomer charge on the extent of ion accumulation near B-DNA oligonucleotides, as a function of [Na] and [P].

Animals↗
PubMed1995

Salt-nucleic acid interactions.

Coulombic interactions of salt ions with polymeric and oligomeric nucleic acids in solution have large and distinctive effects on ion distributions, on thermodynamic coefficients, and hence on equilibrium processes involving nucleic acids, such as their conformational transitions and binding interactions. In experimental or theoretical studies where an oligonucleotide is taken to represent the corresponding polynucleotide, the impact of coulombic end effects on molecular and thermodynamic properties must be taken into account. Observable consequences of coulombic interactions in nucleic acid solutions have been calculated by using models with varying degrees of detail and methods formulated at varying levels of rigor. From comparisons of experimental results with predictions of the prevalent theoretical approaches, this review concludes that the more rigorous methods have proved capable of accounting for thermodynamic (and some molecular) consequences of coulombic interactions with a minimal number of preaveraged parameters that represent the most important structural features of the nucleic acid solution.

Electrolytes↗
PubMed1994

Conformational transitions of duplex and triplex nucleic acid helices: thermodynamic analysis of effects of salt concentration on stability using preferential interaction coefficients.

For order-disorder transitions of double- and triple-stranded nucleic acid helices, the midpoint temperatures Tm depend strongly on a +/-, the mean ionic activity of uniunivalent salt. Experimental determinations of dTm/d ln a +/- and of the enthalpy change (delta H(o)) accompanying the transition in excess salt permit evaluation of delta gamma, the stoichiometrically weighted combination of preferential interaction coefficients, each of which reflects thermodynamic effects of interactions of salt ions with a reactant or product of the conformational transition (formula; see text) Here delta H(o) is defined per mole of nucleotide by analogy to delta gamma. Application of Eq. 1 to experimental values of delta H(o) and Tm yields values of delta gamma for the denaturation of B-DNA over the range of NaCl concentrations 0.01-0.20 M (Privalov et al. (1969), Biopolymers 8,559) and for each of four order-disorder transitions of poly rA.(poly rU)n, n = 1, 2 over the range of NaCl concentrations 0.01-1.0 M (Krakauer and Sturtevant (1968), Biopolymers 6, 491). For denaturation of duplexes and triplexes, delta gamma is negative and not significantly dependent on a +/-, but delta gamma is positive and dependent on a +/- for the disproportionation transition of poly rA.poly rU duplexes. Quantitative interpretations of these trends and magnitudes of delta gamma in terms of coulombic and excluded volume effects are obtained by fitting separately each of the two sets of thermodynamic data using Eq. 1 with delta gamma PB evaluated from the cylindrically symmetric Poisson-Boltzmann (PB) equation for a standard model of salt-polyelectrolyte solutions. The only structural parameters required by this model are: b, the mean axial distance between the projections of adjacent polyion charges onto the cylindrical axis; and a, the mean distance of closest approach between a salt ion center and the cylindrical axis. Fixing bMS and aMS for the multi-stranded (ordered) conformations, we determined the corresponding best fitted values of bSS and aSS for single-stranded RNA and DNA. The resulting best fitted values of aSS are systematically less than aDS by 2-4 A. Uncertainty in the best-fitted values of bSS is significantly lower than in the aSS, because bMS is known with relatively high precision and because the larger uncertainty in aMS has a relatively small effect on the best-fitted values of bSS:bSS = 3.2 +/- 0.6 A for single-stranded poly rA and poly rU; and bSS = 3.4 +/- 0.2 A for single-stranded DNA. These values are approximately one-halt of those expected for a fully extended single-stranded conformation. With the best fitted values of ass and bss, our calculations of delta gamma PB are in close quantitative agreement with experimental observations on each of five nucleic acid order-disorder transitions.

DNA↗
PubMed1994

Changes in umbilical arterial and venous blood flow velocity waveforms during late decelerations of the fetal heart rate.

OBJECTIVE: To compare umbilical arterial and venous Doppler velocity waveforms during labor in fetuses with normal heart rate tracings and fetuses with late decelerations. METHODS: During labor, umbilical arterial and venous Doppler flow velocity waveforms were obtained between and during contractions in 20 fetuses (ten with normal heart rate tracings and ten with late decelerations). The umbilical arterial systolic-diastolic (S/D) velocity ratios were compared, and umbilical venous velocities were examined for the presence or absence of venous pulsations. RESULTS: Fetuses with late decelerations had a significant increase in the umbilical arterial S/D ratio between contractions compared to normal fetuses (2.43 +/- 0.74 versus 1.56 +/- 0.27, P = .003). There was no significant difference in S/D ratios obtained between contractions compared with those obtained during contractions in either the normal or late deceleration group. Umbilical venous pulsations were significantly more common (90 versus 0%, P < .00001) during contractions in fetuses with late decelerations; umbilical venous pulsations were not seen in these fetuses between contractions and were not present at any time in fetuses with normal heart rate tracings. CONCLUSIONS: Increased umbilical arterial velocity ratios and the presence of umbilical venous pulsations during contractions in fetuses with late decelerations suggest that the cardiovascular pathophysiology of late decelerations involves changes in placental resistance as well as cardiac performance. The presence of umbilical venous pulsations during late decelerations is consistent with the hypoxic fetal cardiovascular changes (hypertension and myocardial depression) previously reported from animal studies.

Apgar Score↗
PubMed1993

Hyperlipoproteinemia in adults with renal disease.

Hyperlipoproteinemia is common in patients with renal disease, but increased lipids are only one of several risk factors frequently identified for coronary artery disease. Before treatment options are instituted, renal disease status, current medications, and possible interactions between drugs must be considered. Hypertriglyceridemia is common in patients with renal failure; therapeutic options are influenced by the levels of serum triglycerides and high-density lipoprotein cholesterol. If nonsteroidal drugs improve renal function and decrease proteinuria in patients with renal disease, hyperlipidemia frequently abates. Interactions between drugs are important considerations when lipid-lowering drug treatment is prescribed in recipients of renal transplants.

Adult↗
PubMed1992

Weight change and serum lipoproteins in recipients of renal allografts.

Hyperlipoproteinemia is common in recipients of renal allografts. In this study, serum lipids and some possible contributing factors--weight gain, weight relative to ideal body weight, daily dose of prednisone, serum creatinine, 24-hour urinary protein, and diabetes mellitus--were assessed in 100 patients. At the end of the first year after transplantation, 57 of the 100 patients had total serum cholesterol concentrations of 240 mg/dl or more--40 of 75 patients without diabetes and 17 of 25 with diabetes. The mean values for weight gain (11.2 kg) and actual weight relative to ideal body weight (19.4 kg) were significantly greater (P = 0.029 and P = 0.01, respectively) in the subgroup of patients without diabetes who had total serum cholesterol values of 240 mg/dl or more at 1 year after transplantation than in those with values of less than 240 mg/dl. The daily dose of prednisone and the serum creatinine levels were similar in these two subgroups. The 24-hour urinary protein measurements were greater at 1 month than at 1 year in both patients with and those without diabetes. Perhaps the initial dietary advice for patients who have undergone renal transplantation should emphasize control of total caloric intake; subsequently, intake of cholesterol and fat can be modified in those patients who have persistent hyperlipoproteinemia.

Adult↗
PubMed1991

Relative affinities of divalent polyamines and of their N-methylated analogues for helical DNA determined by 23Na NMR.

Interactions of divalent polyamines with double-helical DNA in aqueous solution are investigated by monitoring the decrease in 23Na NMR relaxation rates as NaDNA is titrated with H3N(+)-(CH2)m-+NH3, where m = 3, 4, 5, or 6. Analogous measurements are made for the same homologous series of methylated polyamines (methonium ions). The dependence of the 23Na relaxation rates on the amount of added divalent cation (M2+) is analyzed quantitatively in terms of a two-state model. The sodium ions are assumed to be in rapid exchange between a "bound" state, where they are close enough to DNA so that it affects their relaxation rate, and a "free" state in bulk solution, where their relaxation rate is the same as in solutions containing no DNA. The distribution of Na+ and M2+ between these states is described quantitatively in terms of an ion-exchange parameter: DM = (pMB)(1-pNaB)n/(pNaB)n(1-pMB), where pNaB and pMB are the fractions of Na+ and M2+ that are close enough to DNA to be considered bound (by the NMR criterion), and n is the number of sodium ions displaced from DNA by the binding of one M2+ ion. For each of the polyamines and methonium ions investigated here, equations derived from this two-state model yield acceptable fittings of the titration curves if roNa, the number of sodium ions bound per DNA phosphate when no competing cations are present, is assigned a value between 0.6 and 1.00. Within this range, changing the value assigned to roNa does change the best-fitted values of DM determined for these polyamines (DH) and for the methonium ions (DMe) but does not alter the following conclusions about the trends in these parameters. (1) For polyamines and methonium ions of the same m, DH exceeds DMe by factors that are significantly larger for m = 3 and 4 than for m = 5 and 6. (2) DH for m = 3 and 4 is larger than DH for m = 5 and 6. (3) DMe for m = 3 and 4 is smaller than DMe for m = 5 and 6.

Bis-Trimethylammonium Compounds↗