Publisher Summary The chapter describes the understanding of the physics and physical chemistry of sickle cell hemoglobin polymerization in solutions and in red cells. The polymerization of sickle cell hemoglobin has probably become the best understood of all protein self-assembly systems. The structure of the hemoglobin S molecule, the structure of the various aggregated forms of hemoglobin S, and the structural analysis of the polymers are discussed in the chapter. The chapter discusses the thermodynamics of hemoglobin S polymerization, and includes a description of the nonideal behavior of concentrated hemoglobin S solutions and the effects of physiologically relevant variables, especially oxygen, and the presence of non-S hemoglobins on the polymerization process. Understanding the polymerization process is not only important for understanding the pathophysiology of sickle cell disease, but is critical to the major problem of developing a specific therapy that could be used in the treatment of patients. The kinetic and thermodynamic studies have played a major role by providing relevant and sensitive assays for potential therapeutic agents. The results of the thermodynamic and kinetic studies of solutions are used to explain various properties of cells, including morphological and rheological properties.

Sickle cell hemoglobin polymerization.

Hemoglobin S gelation and sickle cell disease.

Kinetics of sickle hemoglobin polymerization. I. Studies using temperature-jump and laser photolysis techniques

The intracellular polymerization of sickle hemoglobin and its relevance to sickle cell disease

Kinetic studies on solutions of purified haemoglobin S indicate that the rate of intracellular polymerization is an important variable in the pathophysiology of sickle cell disease. Until now, however, no experimental technique has been available to measure directly the kinetics of intracellular polymerization. Indirect methods, which use visual determination of cellular shape changes or changes in filterability of red cell suspensions, have given apparently conflicting results. Here we report our initial results on the application of a laser-photolysis, light scattering technique to measure directly the kinetics of haemoglobin S polymerization in single red cells. In our experiment, deoxyhaemoglobin S is rapidly formed by photolysing the carbon monoxide complex with an argon ion laser focused inside the cell, and the change in scattered light is used to detect the appearance of polymer. We find a very wide distribution of delay times, ranging from 1 ms to greater than 100 s, indicating that the polymerization inside red cells proceeds by the same nucleation and growth mechanism as in solutions of purified haemoglobin S.

Kinetics of sickle haemoglobin polymerization in single red cells

The effect of erythrocyte membrane preparations on the polymerization of sickle hemoglobin.

IgG4-related disease (IgG4-RD) is a fibro-inflammatory disease that can affect multiple organs. Autoimmune pancreatitis type 1 is a manifestation of IgG4-RD and can often mimic tumor-like masses. Autoimmune phenomena following COVID-19 mRNA vaccination are being increasingly reported. Currently, there are no cases in which IgG4-RD involving the hepatobiliary system has been reported following the COVID-19 vaccination. We present the first case of IgG4-RD and AIP type 1 to be associated with the mRNA-based COVID-19 vaccination.

https://hepatologyforum.org/storage/upload/pdfs/1658994242-en.pdf

Acute liver injury and IgG4-related autoimmune pancreatitis following mRNA-based COVID-19 vaccination

Postoperative myocardial injury and outcomes in liver and kidney transplant patients.

The spontaneous regression or remission (SR) of cancer, often described as the partial or complete disappearance of a malignant tumor in the absence of all medical treatment and therapy, is a well-documented phenomenon. With efforts ongoing to establish cancer treatments that limit undesirable outcomes and adverse effects, these uncommon occurrences of SR carry significant implications for novel therapies and warrant further investigation. While several case studies have reported instances of SR in gastrointestinal (GI) malignancies, a comprehensive review of previous manifestations of SR in the GI tract remains lacking. The inclusion criteria for the rare phenomenon are also in need of an appropriate update that takes recent scientific advancements and emerging new medical technologies into account. Our analysis of 390 cases of SR in the GI tract focuses primarily on neoplasms of the hepatobiliary system and proposes an updated version of the older inclusion criteria for spontaneous regression.

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The Spontaneous Regression of Primary Gastrointestinal Malignancies: An Observational Review

We have investigated the effect of erythrocyte membrane preparations on the rate of polymerization and the solubility of deoxyhemoglobin S. The kinetics of polymerization were monitored by measuring changes in turbidity of hemoglobin S solutions as a function of time in a temperature-controlled cuvette. The solubility of deoxyhemoglobin S, an equilibrium measurement, was determined by measuring the hemoglobin concentration of the supernatant following centrifugation of the polymerized hemoglobin S solution. The solubility of deoxyhemoglobin S was unaffected by the presence of red cell membrane ghosts, inside-out red cell vesicles, or inside-out vesicles enriched in erythrocyte spectrin and actin (Bands 1, 2, and 5) in the hemoglobin solution. Furthermore, inside-out vesicles had no significant effect on the kinetics of polymerization. The addition of erythrocyte membrane ghosts to the hemoglobin solution, in ratios approximating that of the intact red cell, increased the rate of polymerization up to 8-fold. However, when corrections were made for the excluded volume contributed by the membrane ghosts, the enhancement of the rate of polymerization was reduced to less than 3-fold. These results fail to show significant facilitation of intracellular sickling by nucleation sites on the red cell membrane.

A T Lalos

Papers

The effect of erythrocyte membrane preparations on the polymerization of sickle hemoglobin.

Acute liver injury and IgG4-related autoimmune pancreatitis following mRNA-based COVID-19 vaccination

Postoperative myocardial injury and outcomes in liver and kidney transplant patients.

The Spontaneous Regression of Primary Gastrointestinal Malignancies: An Observational Review

Effects of red cell membrane on the polymerization of sickle hemoglobin.