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A Mikkelsen

Publications and source records attributed to A Mikkelsen.

At least 37 records · Page 2Linked to original sources
PubMed1995

Acid-catalysed reduction of ferrylmyoglobin: product distribution and kinetics of autoreduction and reduction by NADH.

The pH dependence of iron(II)/iron(III) product distribution, following reduction of the hypervalent iron in equine ferrylmyoglobin by the protein moiety of the pigment (so-called autoreduction) and by NADH (nicotinamide adenine dinucleotide, reduced) and the rate of reduction was found to depend different on pH. Autoreduction is specific acid catalysed and has a more modest temperature dependence than autoxidation of oxymyoglobin, with the activation parameters delta H# = 58.5 +/- 0.4 kJ.mol-1 and delta S# = 2.7 +/- 0.1 J.mol-1.K-1 in 0.16 mol.l-1 NaCl. The product of autoreduction is the iron(III) pigment metmyoglobin, which is slightly modified in the protein moiety. The reaction has a positive kinetic salt effect from which it is deduced that the reactive centre of ferrylmyoglobin has a charge of +1 in agreement with the structure Fe(IV) = O. Reduction by NADH involves parallel reactions of two pigment forms in acid/base equilibrium with each other with a pKa equal to 4.9, both forms yielding metmyoglobin as well as the iron(II) pigment, oxymyoglobin, as products. The protonated form reacts faster than the deprotonated form, and two-electron transfer has greater importance for the protonated form with a limiting Fe(II)/Fe(III) product ratio of 0.6 in acidic solution compared to 0.12 in alkaline solution. A square root dependence of rate on NADH concentration suggests involvement of NAD.radicals with a disproportionation as the termination reaction.

Animals↗
PubMed1991

The menopausal syndrome: a factor analytic replication.

The authors contend that conclusions regarding the existence of a menopausal syndrome based on clinical trials with oestrogen therapy cannot be generalized to the general population. As an alternative strategy for investigating the nature of the menopausal syndrome the authors performed a factor analysis of the results from a symptom checklist. The list was included in a postal questionnaire sent to a representative sample of 2349 women aged between 45 and 55 years residing in the city of Oslo, Norway. A varimax, rotated five-factor solution yielded the best result both theoretically and empirically. The five factors were labelled as vague somatic complaints, nervousness, mood lability, vasomotor complaints and urogenital complaints. Five variables were constructed on the basis of the factor scores. One-way analysis of variance showed that vasomotor complaints associated with excessive sweating, hot flushes and vaginal dryness, constituted the only variable significantly related to menopausal development. The latter was measured according to time elapsed since the last menstrual period.

Climacteric↗
PubMed1991

Psychosocial determinants of climacteric complaints.

A total of 2349 Norwegian women aged 45-55 years, were investigated using postal questionnaires. Associations between menopausal development, psychosocial factors and climacteric complaints were analyzed. Factor analysis of 24 climacteric complaints identified five factors (vague somatic complaints, nervous complaints, mood lability, vasomotor and urogenital complaints) which were analyzed in relation to stage of menopausal development and a number of psychosocial variables. Five types of variable contributed to the variance in the five previously identified factors, viz. style of reacting to menstruation earlier in life, mother's climacteric complaints, negative expectations regarding the menopause, social network, sociodemographic factors, and chronological age. Menopausal development played a modest role in explaining the variance in all except vasomotor complaints, the latter being associated with current cigarette smoking. Traditional sex-role identification was associated with nervous complaints. The authors conclude that hot flushes, excessive sweating and vaginal dryness are the only complaints clearly attributable to menopausal development.

Affect↗
PubMed1989

Frequency dependence of the shear moduli of spectrin studied using a multiple lumped resonator viscoelastometer.

The frequency dependence (119-7860 Hz) of the storage and loss shear moduli, G' and G'', of human erythrocyte spectrin dimer crude solutions at 22.5 degrees C has been measured using a Birnboim-Schrag multiple lumped resonator viscoelastometer. The measurements were carried out on solutions of ionic strength 1 mM containing 1.1-3.7 mg ml-1 spectrin. This corresponds to the terminal zone for G' and G''. Analysis of the data using the standard theory of hybrid relaxation spectra yields a relaxation time of 22.5 +/- 1 microseconds. The pure spectrin dimer relaxation time is estimated to be 16 +/- 3 microseconds. This result suggests that at an ionic strength of 1 mM, the spectrin dimers are extended and that the main relaxation process is simple end-over-end rotation.

Biophysics↗
PubMed1986

The molecular basis of erythrocyte shape.

Recent discoveries about the molecular organization and physical properties of the mammalian erythrocyte membrane and its associated structural proteins can now be used to explain, and may eventually be used to predict, the shape of the erythrocyte. Such explanations are possible because the relatively few structural proteins of the erythrocyte are regularly distributed over the entire cytoplasmic surface of the cell membrane and because the well-understood topological associations of these proteins seem to be stable in comparison with the time required for the cell to change shape. These simplifications make the erythrocyte the first nonmuscle cell for which it will be possible to extend our knowledge of molecular interactions to the next hierarchical level of organization that deals with shape and shape transformations.

Energy Metabolism↗
PubMed1986

The human erythrocyte membrane skeleton may be an ionic gel. III. Micropipette aspiration of unswollen erythrocytes.

We have carried out a theoretical analysis of micropipette aspiration of unswollen erythrocytes using the protein-gel-lipid-bilayer membrane model and taking into account that the modulus of area compression of the membrane skeleton may depend on the environmental conditions. Our analysis shows that the aspiration pressure needed to obtain a certain membrane projection length is strongly dependent on the ratio between the membrane skeleton modulus of area compression and the elastic shear modulus. Our analysis therefore predicts that micropipette aspiration of unswollen erythrocytes may be a sensitive method for detection of changes in this ratio. The analysis thus also shows that micropipette aspiration of unswollen erythrocytes can not be used to determine the membrane shear modulus unless something is known about the membrane skeleton modulus of area compression.

Biophysical Phenomena↗
PubMed1986

The human erythrocyte membrane skeleton may be an ionic gel. I. Membrane mechanochemical properties.

Biochemical and biophysical observations indicate that the erythrocyte membrane skeleton is composed of a swollen network of long, flexible and ionizable macromolecules located at the cytoplasmic surface of the fluid membrane lipid bilayer. We have analyzed the mechanochemical properties of the erythrocyte membrane assuming that the membrane skeleton constitutes an ionic gel (swollen ionic elastomer). Using recently established statistical thermodynamic theory for such gels, our analysis yields mathematical expressions for the mechanochemical properties of erythrocyte membranes that incorporate membrane molecular parameters to an extent not achieved previously. The erythrocyte membrane elastic shear modulus and maximum elastic extension ratio predicted by our membrane model are in quantitative agreement with reported values for these parameters. The gel theory predicts further that the membrane skeleton modulus of area compression, KG, may be small as well as large relative to the membrane elastic shear modulus, G, depending on the environmental conditions. Our analysis shows that the ratio between these two parameters affects both the geometry and the stability of the favoured cell shapes.

Erythrocyte Membrane↗
PubMed1986

The human erythrocyte membrane skeleton may be an ionic gel. II. Numerical analyses of cell shapes and shape transformations.

In the first paper in this series (Stokke et al. Eur Biophys J 1986, 13:203-218) we developed the general theory of the mechanochemical properties and the elastic free energy of the protein gel--lipid bilayer membrane model. Here we report on an extensive numerical analysis of the human erythrocyte shapes and shape transformations predicted by this new cell membrane model. We have calculated the total elastic free energy of deformation of four different cell shape classes: disc-shaped cells, cup-shaped cells, crenated cells, and cells with membrane invaginations. We find that which of these shape classes is favoured depends strongly on the spectrin gel osmotic tension, IIGu, and the surface tensions, IIEu and IIPu, of the extracellular and protoplasmic halves of the membrane lipid bilayer, respectively. For constant ratio IIEu/IIPu greater than O large negative or positive values of IIGu favour respectively the crenated and invaginated cell shape classes. For small absolute values of IIGu, IIEu, and IIPu, biconcave or cup-shaped cells are the stable ones. Our numerical analysis shows that the higher the membrane skeleton compressibility is, the smaller are the values of IIGu needed to induce cell shape transformation. We find that the stable and metastable shapes of discocytes and stomatocytes generally depend both on the shape of the stressfree membrane skeleton and the membrane skeleton compressibility.

Elasticity↗
PubMed1986

Spectrin, human erythrocyte shapes, and mechanochemical properties.

Physical studies of human erythrocyte spectrin indicate that isolated spectrin dimers and tetramers in solution are worm-like coils with a persistence length of approximately 20 nm. This finding, the known polyelectrolytic nature of spectrin, and other structural information about spectrin and the membrane skeleton molecular organization have lead us to the hypothesis that the human erythrocyte membrane skeleton constitutes a two-dimensional ionic gel (swollen ionic elastomer). This concept is incorporated in what we refer to as the protein gel-lipid bilayer membrane model. The model accounts quantitatively for red elastic shear modulus and the maximum elastic extension ratio reported for the human erythrocytes membrane. Gel theory further predicts that depending on the environmental conditions, the membrane skeleton modulus of area compression may be small or large relative to the membrane elastic shear modulus. Our analyses show that the ratio between these two parameters affects both the geometry and the stability of the favored cell shapes and that the higher the membrane skeleton compressibility the smaller the values of the gel tension needed to induce cell shape transformations. The main virtue of the protein gel-lipid bilayer membrane model is that it offers a novel theoretical and molecular basis for the various mechanical properties of the membrane skeleton such as the membrane skeleton modulus of area compression and osmotic tension, and the effects of these properties on local membrane skeleton density, cell shape, and shape transformations.

Erythrocyte Membrane↗
PubMed1985

An electrophoretic device concentrating charged macromolecules to a predetermined final solution volume.

An apparatus for electrophoretic concentration of charged macromolecules to a predetermined final solution volume has been developed. The concentration process has a yield of near 100%, which implies that it is possible to predetermine the final macromolecule concentration as well. Both the final macromolecule solution volume and concentration are nearly independent of the electrophoresis time when it exceeds a certain minimum value. The electric field strength across the boundary containing the concentrated macromolecule solution is very low. This considerably reduces macromolecule aggregation, adsorption, and denaturation at this boundary compared to conventional electrophoretic concentrator designs. Both one-stage and two-stage versions of the apparatus have been developed. The one-stage version easily yields a 10-fold and the two-stage version a 50-fold concentration of the macromolecules. Typical macromolecule solution start volumes are 20-50 ml.

Electrochemistry↗
PubMed1985

Human erythrocyte spectrin dimer intrinsic viscosity: temperature dependence and implications for the molecular basis of the erythrocyte membrane free energy.

We have determined experimentally the temperature dependence of human erythrocyte spectrin dimer intrinsic viscosity at shear rates 8-12 s-1 using a Cartesian diver viscometer. We find that the intrinsic viscosity decreases from 43 +/- 3 ml/g at 4 degrees C to 34 +/- 3 ml/g when the temperature is increased to 38 degrees C. Our results show that spectrin dimers are flexible worm-like macromolecules with persistence length about 20 nm and that the mean square end-to-end distance for this worm-like macromolecules decreases when the temperature is increased. This implies that the spectrin dimer internal energy decreases when the end-to-end distance is increased and that the free energy increase associated with making the end-to-end distance longer than the equilibrium value for the free molecules is of entropic origin. The temperature dependence of the erythrocyte membrane shear modulus reported previously in the literature therefore appears mainly to be due to temperature dependent alterations in the membrane skeleton topology.

Erythrocyte Membrane↗
PubMed1985

Some viscoelastic properties of human erythrocyte spectrin networks end-linked in vitro.

We have succeeded in making macroscopic networks of end-linked human erythrocyte spectrin. The network junctions were made using erythrocyte protein 4.1 irreversibly attached to 5 nm (diameter) colloidal gold particles. Rotary shadowing electron microscopy verifies that the protein 4.1-labelled colloidal gold particles bind only to the tail end of the spectrin molecules. Electron micrographs of protein 4.1-labelled colloidal gold particles incubated at 4 degrees C with spectrin dimers reveal that 1-5 spectrin dimers attach to each protein 4.1-labelled colloidal gold particle yielding a spider-like appearance of these complexes. Incubation with a low concentration of spectrin tetramers instead of dimers leads to extensive formation of spectrin microaggregates whereas use of spectrin concentrations higher than 3 mg/ml and a molar ratio between spectrin tetramers and protein 4.1/Au of 4 leads to formation of macroscopic spectrin networks. We have quantitated the viscoelastic properties of such end-linked macroscopic spectrin networks using a gravitational pendulum viscoelastometer. We find that in vitro end-linked spectrin networks can be described by linear viscoelastic theory. The dynamic storage modulus increases almost linearly with the spectrin-protein 4.1/gold particle concentration when the spectrin concentration exceeds about 3 mg/ml and the molar ratio between spectrin tetramers and protein 4.1/Au is 4. At a spectrin concentration of 6 mg/ml and the same ratio between spectrin and protein 4.1/Au, we find a dynamic storage modulus at low frequency of about 80 dyn/cm2. This is in adequate agreement with what is predicted by simple elastomer theory.

Blood Proteins↗
PubMed1985

A computerized low-shear pendulum viscoelastometer, stress-relaxation, shear creep, and dynamic elastic moduli measurements of soft biogels.

A computerized low-shear pendulum viscoelastometer that is well suited for measurements of the viscoelastic properties of soft biogels is described. The instrument has three modes of operation: (i) measurement of dynamic elastic moduli, (ii) stress relaxation, and (iii) shear creep-creep recovery. The main mechanical parts of the instrument include a specimen cuvette and a pendulum with a thin metal plate extending into the specimen cuvette. The cuvette and pendulum can undergo independent angular movements relative to a horizontal axis located about 12 cm above the specimen cuvette. The absolute angular position of the cuvette is under on-line computer control through a stepping motor driven micrometer. The angular position of the pendulum relative to the cuvette is measured using an inductive position detector. The necessary software for automatic operation, data acquisition and processing has been developed for all the three modes of operation. The instrument is well suited for measurements of dynamic elastic moduli in the range 0.02-150 dyn/cm2. Calibration data obtained using 100% ethanol are presented. The instrument suitability for measurements of stress relaxation and shear creep-creep recovery is illustrated by presenting the results of such measurements on a 5.5-mg/ml erythrocyte spectrin gel in isotonic solution.

Biophysical Phenomena↗
PubMed1985

A practical, high-resolution, microcomputer-based method for the analysis of relaxation data exhibiting multicomponent exponential decays.

We have developed and tested a practical, rapid, high-resolution, microcomputer-based method for the analysis of multicomponent exponential decays. The analysis utilizes the Fourier deconvolution technique and includes methods to reduce noise both in the input data and in the results. The developed method is particularly well suited for analysing decays consisting of a wide range of decay times. The method resolves two exponential decays differing by a factor of two when the input data are mathematically generated and without noise, and resolves two decays differing by a factor of three when 2% Gaussian noise is present in the same data. The method lends itself to routine analysis of any relaxation process consisting of exponential decays, including biomedical applications such as enzyme kinetics, circulatory transport functions, pharmacokinetics, plasma exchange therapy, and analysis of compartmental models for any process.

Birefringence↗
PubMed1984

An electro-optic study of human erythrocyte spectrin dimers. The presence of calcium ions does not alter spectrin flexibility.

In order to determine whether the presence of Ca2+ increases the stiffness of the highly elongated and flexible spectrin molecules, we have carried out a birefringence relaxation study of isolated human erythrocyte spectrin dimers. Our measurements indicate no significant change in the flexibility of spectrin in solutions containing 0-10(-3) M Ca2+. This finding indicates that decreased spectrin flexibility is not the major functional mechanism underlying the decreased erythrocyte deformability reported as result of elevated intracellular levels of Ca2+. We find that the persistence length of spectrin dimers is less than 20 nm and is not dependent on the Ca2+ concentration.

Calcium↗