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R W Briehl

Publications and source records attributed to R W Briehl.

35 records · Page 2Linked to original sources
PubMed1982

The effects of shear on the delay time for gelation of hemoglobin S.

Intraerythrocytic gelation of deoxyhemoglobin S is the immediate cause of red cell deformation and rigidification in sickle cell disease. Hence the rheology of hemoglobin S gels, heretofore little studied, plays a central role in pathogenesis. I have shown previously [2] that unsheared gels are solid-like whereas sheared gels are viscous in character. In the present studies the delay (nucleation) time for gelation (after a temperature jump) was examined in the absence and presence of shear, employing a sharp rise in viscosity as the end point of the delay time. Shearing rates in the range from 1.92 to 384 s-1 progressively accelerate the delay time. In another series of experiments the temperature jump was carried out in the absence of shear, shear being instituted later in the delay period. There was a sparing effect of the time of incubation in the absence of shear on the subsequent time under shear needed to induce gelation. A linear relation was observed between these two parameters, indicating that shear operates with constant efficacy in accelerating gelation, independent of when in the delay time it is applied. This suggests that the mechanism of assembly is the same throughout the period. Since shear probably operates through the breakage of fibers with the creation of new growth centers, the results also suggest that long, breakable, fibers are present even relatively early in the delay period. Values were obtained for delay time under shear and (by extrapolation) delay time under no shear. The temperature dependence (and hence apparent activation energy) of the latter is larger than that of the former; i.e. the effect of shear in shortening delay time is more marked as temperatures are lowered. With respect to pathogenesis, these results suggest that intraerythrocytic shearing may be detrimental because it accelerates gelation. On the other hand shearing of gels converts them from solid-like to viscous, and hence more deformable, systems; this effect of shear might be expected to ameliorate pathogenesis. Consequently, the pathogenic effects of intraerythrocytic shearing may depend on when the shear is applied.

Anemia, Sickle Cell↗
PubMed1980

Solid-like behaviour of unsheared sickle haemoglobin gels and the effects of shear.

Pathogenesis in sickle cell disease depends on the polymerization of deoxyhaemoglobin S into long fibres followed by 'gel' formation. The 'gelation' renders the affected erythrocytes less deformable than normal so that they obstruct the microvasculature and the 'gelation' process has been one of the targets for the development of therapeutic treatments of sickle cell disease. 'Gelation', however, acts through the rheological properties it induces and rheological abnormalities are therefore the immediate bases of pathogenesis. Although there has been very little study of the rheology of haemoglobin S haemolysates, the 'gels' are generally considered to be highly viscous and thixotropic on the basis of gross observation. Limited and generally qualitative observations show that high viscosity depends on deoxygenation and exhibits hysteresis in gelling/ungelling cycles; also that shearing accelerates gelation and can induce formation of fibre aggregates and crystals in suspension which, in contrast to the 'gel', are fluid. Using transient and steady state methods it is shown here that unsheared sickle deoxyhaemoglobin preparations are solid-like, consistent with a gel-like nature, whereas shearing converts them to thixotropic viscous systems. These results underline the marked variation and thixotropy the system can undergo and may be relevant to the pathogenesis, clinical course and therapy of sickle cell disease.

Gels↗
PubMed1979

Tactoidal state and phase transitions in systems of linear polymers of variable length.

The tactoidal state in systems containing long, rod-like molecules consists of partially aligned solute molecules in equilibrium with and at a concentration not much higher than that in the conjugate isotropic phase. Under the liquid lattice model of Flory [Proc. R. Soc. London Ser. A, (1956) 234, 73-89], as well as under other models, tactoid formation by molecules of fixed axial ratio depends on nonideality induced by excluded volumes; the process is wholly entropy driven and requires no direct interactions between rods. Many rod-like biological polymers exhibit reversible polymerization, so that axial ratio and length are not fixed. Polymerization and rod length will then not only induce nonideality, alignment, and phase separation, but will be affected by these. In this work these interrelations are treated under the model of Flory, modified to include a free energy of polymerization and to permit reversible changes in rod length. The primary conclusion is that, in contrast to the situation for fixed lengths, excluded volume-dependent nonideality alone does not suffice to induce a tactoidal phase separation. In the absence of attractions or repulsions between rods the anisotropic phase is highly concentrated. This phase only becomes tactoidal when a minimal level of repulsive interaction between rods is reached. Under this model, tactoid formation in systems such as deoxygenated hemoglobin S and tobacco mosaic virus depends on repulsive interactions or metastability or both. As a secondary result it is shown that rod length in the anisotropic phase is much greater than in the conjugate isotropic phase.

Hemoglobin, Sickle↗
PubMed1970

The interaction of 2,3-diphosphoglycerate with various human hemoglobins.

Oxygen equilibria were measured on a number of human hemoglobins, which had been "stripped" of organic phosphates and isolated by column chromatography. In the presence of 2 x 10(-4) M 2,3-diphosphoglycerate (2,3-DPG), the P(50) of hemoglobins A, A(2), S, and C increased about twofold, signifying a substantial and equal decrease in oxygen affinity. Furthermore, hemoglobins Chesapeake and M(Milwaukee-1) which have intrinsically high and low oxygen affinities, respectively, also showed a twofold increase in P(50) in the presence of 2 x 10(-4) M 2,3-DPG. In comparison to these, hemoglobins A(IC) and F were less reactive with 2,3-DPG while hemoglobin F(I) showed virtually no reactivity. The N-terminal amino of each beta-chain of hemoglobin A(IC) is linked to a hexose. In hemoglobin F(I) the N-terminal amino of each gamma-chain is acetylated. These results suggest that the N-terminal amino groups of the non-alpha-chains are involved in the binding of 2,3-DPG to hemoglobin.

Chromatography, DEAE-Cellulose↗
PubMed1965

Haemoglobins of invertebrate tissues. Nerve haemoglobins of Aphrodite, Aplysia and Halosydna.

1. The occurrence of haemoglobin in invertebrate nerves is surveyed. Haemoglobin was observed in the nerves and ganglia of the marine nematode Amphiporus sp. and of the polychaet annelid Halosydna sp. 2. Haemoglobins from the nerve and ganglia of the polychaet annelid Aphrodite aculeata L. and from the nerve of the gastropod mollusc Aplysia californica have been partially purified. The haem in each case was identified as iron protoporphyrin IX. 3. The minimum molecular weight of Aphrodite nerve haemoglobin deduced from the haem content and amino acid analysis is 17090, in agreement with the molecular weight 15600+/-1000 determined by sedimentation equilibrium. 4. The molecular weight of Aplysia nerve haemoglobin was determined by sedimentation equilibrium to be 16400+/-1000. 5. The oxygen dissociation curves are hyperbolic. Half-saturation is achieved at 1.1mm. Hg for Aphrodite nerve haemoglobin and at 4.0mm. Hg for Aplysia nerve haemoglobin. The coefficients for partition between carbon monoxide and oxygen are: Aphrodite nerve haemoglobin, 167; Aplysia nerve haemoglobin, 116. 6. The ferrous haemoglobins combine with cyanide. 7. We conclude that the intracellular haemoglobins of muscle and nerve are similar.

Animals↗