scholarly journals THE OXYGEN EQUILIBRIUM OF THE HEMOGLOBIN OF THE EEL, ANGUILLA ROSTRATA

1951 ◽  
Vol 35 (1) ◽  
pp. 41-44 ◽  
Author(s):  
Austen Riggs
Keyword(s):  
Hill Equation ◽  
Anguilla Rostrata ◽  
Hill’S Equation ◽  
Oxygen Equilibrium ◽  
Equilibrium Function ◽  
Hill's Equation ◽  
The Hill

Kawamoto had reported that eel hemoglobin has a hyperbolic oxygen equilibrium function, with n in the Hill equation equal to 1. On the basis of Kawamoto's data and with new measurements, it is shown that the equilibrium function is in fact S-shaped, as in most other vertebrates, and n in Hill's equation equals 1.8.

scholarly journals THE EFFECT OF FORMALDEHYDE ON THE OXYGEN EQUILIBRIUM OF HEMOGLOBIN

1954 ◽  
Vol 37 (6) ◽  
pp. 775-780 ◽  
Author(s):  
Karl F. Guthe
Keyword(s):  
Oxygen Pressure ◽  
Oxygen Affinity ◽  
Sulfhydryl Groups ◽  
Human Hemoglobin ◽  
Hill’S Equation ◽  
Oxygen Equilibrium ◽  
Hill's Equation ◽  
Hemoglobin Molecule

1. When formaldehyde (0.10 M) is added to solutions of human hemoglobin, the oxygen affinity of the hemoglobin increases considerably (more than tenfold near pH 7). The interaction between hemes of the same hemoglobin molecule decreases, as shown by a drop in the value of n in Hill's equation from 2.9 to 1.5 or less. 2. In the presence of formaldehyde, both n and the oxygen pressure for half-saturation fall gradually as the pH rises in the range from pH 6.2 to 7.2. 3. Some of the effect of formaldehyde on the oxygen equilibrium may be due to combination with sulfhydryl groups of the protein, but nitrogenous groups are probably also involved.

scholarly journals THE EQUILIBRIUM BETWEEN CYTOCHROME OXIDASE AND CARBON MONOXIDE

1957 ◽  
Vol 40 (4) ◽  
pp. 593-608 ◽  
Author(s):  
George Wald ◽  
David W. Allen
Keyword(s):  
Carbon Monoxide ◽  
Cytochrome Oxidase ◽  
Hill Equation ◽  
Bohr Effect ◽  
Degree Of Saturation ◽  
Percentage Saturation ◽  
Equilibrium Function ◽  
Hyperbolic Equilibrium ◽  
High Degree ◽  
The Hill

An evolution argument which attempted to trace the development of hemoglobins from such respiratory pigments as cytochrome oxidase presupposed that the latter possesses, in addition to its high affinity for oxygen, an approximately hyperbolic equilibrium function, and little if any Bohr effect (decline in affinity for oxygen with rise in acidity). Since cytochrome oxidase, unlike hemoglobin, is irreversibly oxidized by oxygen, the present experiments examine its combination with carbon monoxide, with which, like hemoglobin, it yields a true equilibrium. In all known hemoglobins the form of the equilibrium function and the vigor of the Bohr effect are similar with carbon monoxide and with oxygen, so that observations involving the former gas are relevant to the relations of the latter. The equilibrium function of cytochrome oxidase with carbon monoxide—percentage saturation vs. partial pressure of CO—is slightly inflected (in the Hill equation n = 1.26; for a hyperbola, n = 1). No Bohr effect is present in the range of pH 7–8. The pressure of carbon monoxide at which half-saturation occurs (p50) is about 0.17 mm. at 10–13°C. The affinity for carbon monoxide is therefore higher than commonly supposed. These properties are consistent with the evolution argument. They are important also for the physiological functioning of cytochrome oxidase, the nearly hyperbolic equilibrium function facilitating a high degree of saturation, and the lack of Bohr effect making this enzyme impervious to hyperacidity. The slight inflection of the equilibrium function shows that the Fe-porphyrin units of cytochrome oxidase interact to a degree, hence that the enzyme must contain more than one such unit per molecule. It is suggested that in cytochrome oxidase two Fe-porphyrin groups may unite with one oxygen in the manner Fe++-O2-Fe++; and that the evolution of hemoglobins proceeded over a first stage in which the hemes were separated so that each combines with only one molecule of oxygen, so tending to remain reduced; to a further stage in which the separated hemes interact through the protein to facilitate one another in combining with oxygen.

XXI—The Whittaker-Hill Equation and the Wave Equation in Paraboloidal Co-ordinates

1967 ◽  
Vol 67 (4) ◽  
pp. 265-276 ◽  
Author(s):  
F. M. Arscott
Keyword(s):  
Wave Equation ◽  
Boundary Value Problems ◽  
Formal Solution ◽  
Boundary Value ◽  
Hill Equation ◽  
Hill’S Equation ◽  
Simple Boundary ◽  
Hill's Equation ◽  
Helmholz Equation

SynopsisThe problem considered is that of obtaining solutions of the Helmholz equation ∇2V + k2V = 0, suitable for use in connection with paraboloidal co-ordinates. In these co-ordinates the Helmholz equation is separable, and each of the separated equations is reducible to Hill's equation with three terms (the Whittaker-Hill equation). The properties of solutions of this equation are developed sufficiently to make possible the formal solution of simple boundary-value problems for paraboloidal surfaces, principally for the case k2 < 0.

scholarly journals THE METAMORPHOSIS OF HEMOGLOBIN IN THE BULLFROG

1951 ◽  
Vol 35 (1) ◽  
pp. 23-40 ◽  
Author(s):  
Austen Riggs
Keyword(s):  
Molecular Weight ◽  
Oxygen Affinity ◽  
Hill’S Equation ◽  
Effect Of Ph ◽  
Oxygen Equilibrium ◽  
Hill's Equation ◽  
Adult Hemoglobin

1. Tadpole and adult hemoglobin do not differ significantly in molecular weight. The molecular weight of both is in the neighborhood of 68,000. 2. Heme-heme interaction as measured by the value of n in Hill's equation is virtually the same—about 2.8—in both tadpole and adult. 3. There appears to be no significant effect of pH upon the oxygen equilibrium of tadpole hemoglobin, in contrast to large Bohr and reverse Bohr effects in the adult. This is taken to mean that during metamorphosis acid groups of globin become sensitive to the oxygenation of heme by some change in the mode of linkage between heme and globin. 4. The oxygen affinity of tadpole hemoglobin is about seven times as great as that of the adult at pH 6 and twice as great at pH 9.

scholarly journals Pharmacodynamics of Daptomycin against Enterococcus faecium and Enterococcus faecalis in the Murine Thigh Infection Model

2018 ◽  
Vol 62 (10) ◽  
Author(s):  
James M. Kidd ◽  
Kamilia Abdelraouf ◽  
Tomefa E. Asempa ◽  
Romney M. Humphries ◽  
David P. Nicolau
Keyword(s):  
Enterococcus Faecalis ◽  
Enterococcus Faecium ◽  
Hill Equation ◽  
Infection Model ◽  
Free Drug Concentration ◽  
Time Curve ◽  
Content Type ◽  
Concentration Time ◽  
The Hill ◽  
Susceptibility Breakpoint

ABSTRACT The Clinical and Laboratory Standards Institute (CLSI) daptomycin MIC susceptibility breakpoint for the treatment of enterococcal infections is ≤4 μg/ml. However, patients receiving daptomycin for the treatment of infections caused by enterococci with MICs of ≤4 μg/ml may experience treatment failures. We assessed the pharmacodynamics of daptomycin against enterococci in a neutropenic murine thigh infection model and determined the exposures necessary for bacteriostasis and a 1-log10-CFU reduction of Enterococcus faecalis and Enterococcus faecium. We further characterized daptomycin efficacy at clinically achievable exposures. Six E. faecium and 6 E. faecalis isolates (daptomycin MICs, 0.5 to 32 μg/ml) were studied. Daptomycin was administered at various doses over 24 h to achieve area under the free drug concentration-time curve-to-MIC ratios (fAUC0–24/MIC) ranging from 1 to 148. Daptomycin regimens that simulate mean human exposures following doses of 6, 8, and 10 mg/kg of body weight/day were also studied. Efficacy was assessed by the differences in the number of log10 CFU per thigh at 24 h. The Hill equation was used to estimate the fAUC0–24/MIC required to achieve bacteriostasis and a 1-log10-CFU reduction. For E. faecium, a 1-log10-CFU reduction required an fAUC0–24/MIC of 12.9 (R2 = 0.71). For E. faecalis, a 1-log10-CFU reduction was not achieved, while the fAUC0–24/MIC required for stasis was 7.2 (R2 = 0.8). With a human-simulated regimen of 6 mg/kg/day, a 1-log10-CFU reduction was observed in 3/3 E. faecium isolates with MICs of <4 μg/ml and 0/3 E. faecium isolates with MICs of ≥4 μg/ml; however, a 1-log10-CFU reduction was not achieved for any of the 6 E. faecalis isolates. These results, alongside clinical data, prompt a reevaluation of the current breakpoint.

On the solution of Hill's equation using Milne's method

1991 ◽  
Vol 24 (9) ◽  
pp. 2069-2081 ◽  
Author(s):  
J A Nunez ◽  
F Bensch ◽  
H J Korsch
Keyword(s):  
Hill’S Equation ◽  
Hill's Equation

Effect of osmotic swelling and shrinkage on Na(+)-K+ pump activity in mammalian cardiac myocytes

1993 ◽  
Vol 265 (5) ◽  
pp. C1201-C1210 ◽  
Author(s):  
D. W. Whalley ◽  
L. C. Hool ◽  
R. E. Ten Eick ◽  
H. H. Rasmussen
Keyword(s):  
Ventricular Myocytes ◽  
Pump Current ◽  
Hill Equation ◽  
Cell Swelling ◽  
Intracellular Na Activity ◽  
Single Ventricular Myocytes ◽  
Hyperosmolar Solutions ◽  
Hill Coefficients ◽  
The Hill ◽  
The Relationship

The effect on the sarcolemmal Na(+)-K+ pump of exposure to anisosmolar solutions was examined using whole cell patch clamping and ion-selective microelectrodes. Na(+)-K+ pump currents were measured in single ventricular myocytes by using pipette Na+ concentrations ([Na]pip) of 0-70 mM. The relationship between [Na]pip and pump current was well described by the Hill equation. The [Na]pip for half-maximal pump current (K0.5) was 21.4 mM in isosmolar (310 mosM) solution. K0.5 was 12.8 mM during cell swelling in hyposmolar solution (240 mosM) and 39.0 mM during cell shrinkage in hyperosmolar solution (464 mosM). The maximal pump currents, derived from the best fit of the Hill equation, and the Hill coefficients were similar in isosmolar, hyposmolar, and hyperosmolar solutions. A sustained (> 20 min) decrease in the intracellular Na+ activity developed during exposure of intact papillary muscles to hyposmolar solutions, and a sustained increase developed during exposure to hyperosmolar solutions. We conclude that osmotic myocyte swelling stimulates the sarcolemmal Na(+)-K+ pump at near-physiological levels of intracellular Na+, whereas shrinkage inhibits the pump. These changes are due to increases and decreases, respectively, in the apparent affinity of the pump for Na+.

Perspective on the relationship between GABAA receptor activity and the apparent potency of an inhibitor

2021 ◽  
Vol 19 ◽  
Author(s):  
Allison L. Germann ◽  
Spencer R. Pierce ◽  
Alex S. Evers ◽  
Joe Henry Steinbach ◽  
Gustav Akk
Keyword(s):  
Gabaa Receptor ◽  
Hill Equation ◽  
Response Relationship ◽  
Inhibition Concentration ◽  
Level Of Activity ◽  
Control Response ◽  
The Hill ◽  
The Relationship ◽  
Inhibition Curve ◽  
Receptor Channel

Background : In electrophysiological experiments inhibition of a receptor-channel, such as the GABAA receptor, is measured by co-applying an agonist producing a predefined control response with an inhibitor to calculate the fraction of the control response remaining in the presence of the inhibitor. The properties of the inhibitor are determined by fitting the inhibition concentration-response relationship to the Hill equation to estimate the midpoint (IC50) of the inhibition curve. Objective: We sought to estimate here the sensitivity of the fitted IC50 to the level of activity of the control response. Methods: The inhibition concentration-response relationships were calculated for models with distinct mechanisms of inhibition. In Model I, the inhibitor acts allosterically to stabilize the resting state of the receptor. In Model II, the inhibitor competes with the agonist for a shared binding site. In Model III, the inhibitor stabilizes the desensitized state. Results: The simulations indicate that the fitted IC50 of the inhibition curve is sensitive to the degree of activity of the control response. In Models I and II, the IC50 of inhibition was increased as the probability of being in the active state (PA) of the control response increased. In Model III, the IC50 of inhibition was reduced at higher PA. Conclusions: We infer that the apparent potency of an inhibitor depends on the PA of the control response. While the calculations were carried out using the activation and inhibition properties that are representative of the GABAA receptor, the principles and conclusions apply to a wide variety of receptor-channels.

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