Assessment of contractility in intact ventricular cardiomyocytes using the dimensionless ‘Frank–Starling Gain’ index

This paper briefly recapitulates the Frank–Starling law of the heart, reviews approaches to establishing diastolic and systolic force–length behaviour in intact isolated cardiomyocytes, and introduces a dimensionless index called ‘Frank–Starling Gain’, calculated as the ratio of slopes of end-systolic and end-diastolic force–length relations. The benefits and limitations of this index are illustrated on the example of regional differences in Guinea pig intact ventricular cardiomyocyte mechanics. Potential applicability of the Frank–Starling Gain for the comparison of cell contractility changes upon stretch will be discussed in the context of intra- and inter-individual variability of cardiomyocyte properties

Antibody response against a possible arthritogenic epitope on human type II collagen induced by anti-idiotypic antibody.

Abstract We reported the presence of three distinct epitopes commonly present on murine and human type II collagen (CII), observed using mAb. To investigate the possible involvement of these epitopes in collagen-induced arthritis, we raised rabbit anti-idiotypic antibodies that may bear the internal image of these epitopes. Anti-idiotypic antibodies developed against three anti-CII mAb designated as 1-5, 2-14, and 2-15 were demonstrated to recognize idiotype expressed on Ag-binding site (paratope) of their related mAb. Anti-CII antibody response specific for a given epitope could be induced in DBA/1J mice upon immunization with anti-idiotypic antibodies coupled to keyhole limpet hemocyanin. Anti-idiotypic antibody to 1-5 antibody in particular could stimulate all DBA/1J mice for production of anti-CII antibody possessing Ag specificity and idiotype similar to those of 1-5 antibody. Although the mice immunized with anti-1-5 antibody alone did not develop arthritis, they did show a much more enhanced antibody response against a given epitope than did control mice non-treated with anti-idiotypic antibody upon the subsequent immunization with human CII. Some of the mice immunized with anti-1-5 antibody and challenged with human CII developed arthritis, whereas the control mice did not. These findings strongly suggest that a common epitope recognized by 1-5 antibody might be involved in the induction of arthritis.</jats:p

Cardiac cell modelling: observations from the heart of the cardiac physiome project

In this manuscript we review the state of cardiac cell modelling in the context of international initiatives such as the IUPS Physiome and Virtual Physiological Human Projects, which aim to integrate computational models across scales and physics. In particular we focus on the relationship between experimental data and model parameterisation across a range of model types and cellular physiological systems. Finally, in the context of parameter identification and model reuse within the Cardiac Physiome, we suggest some future priority areas for this field

Induction of an anti-human type II collagen response by monoclonal anti-idiotypic antibody.

Abstract Several distinct epitopes on human type II collagen were defined by using mAb. The presence of species-specific and species-nonspecific (common) epitopes was thus clarified. Anti-idiotypic mAb (Ab2) was developed against one of the antibodies (Ab1) reactive with species-specific epitopes. Thus Ab2 was demonstrated to recognize an idiotope expressed on the Ag-binding site (paratope) of Ab1, since the binding of Ab1 to human type II collagen was blocked by Ab2, and the binding of Ab2 to Ab1 was inhibited by soluble human type II collagen, but not by murine and bovine type II collagens. DBA/1 mice immunized with Ab2 coupled to keyhole limpet hemocyanin produced an antibody (Ab3) specifically reactive with human type II collagen. It was also demonstrated that Ab3 expressed an idiotype similar to that of Ab1. These findings indicate that anti-idiotypic antibody directed against mAb to human type II collagen mimics a species-specific epitope on human type II collagen. The anti-idiotypic antibody bearing internal image of type II collagen will open the way to isolation of the arthritogenic epitope on type II collagen.</jats:p

Effects of Bepridil on Stretch-Activated BKca Channels and Stretch-Induced Extrasystoles in Isolated Chick Hearts

Various types of mechanosensitive ion channels, including cationic stretch-activated channels (SACNS) and stretch-activated BKca (SAKca) channels, modulate heart rhythm. Bepridil has been used as an antiarrhythmic drug with multiple pharmacological effects; however, whether it is effective for mechanically induced arrhythmia has not been well investigated. To test the effects of Bepridil on SAKca channels activity, cultured chick embryonic ventricular myocytes were used for single-channel recordings. Bepridil significantly reduced the open probability of the SAKca channel (PO). Next, to test the effects of bepridil on stretch-induced extrasystoles (SIE), we used an isolated 2-week-old Langendorff-perfused chick heart. The left ventricle (LV) volume was rapidly changed, and the probability of SIE was calculated in the presence and absence of bepridil, and the effect of the drug was compared with that of Gadolinium (Gd3+). Bepridil decreased the probability of SIE despite its suppressive effects on SAKca channel activity. The effects of Gd3+, which blocks both SAKca and SACNS, on the probability of SIE were the same as those of bepridil. Our results suggest that bepridil blocks not only SAKca channels but possibly also blocks SACNS, and thus decreases the stretch-induced cation influx (stabilizing membrane potential) to compensate and override the effects of the decrease in outward SAKca current (destabilizing membrane potential).</jats:p

Production of T cell-activating monokine of guinea pig macrophages induced by MDP and partial characterization of the monokine.

Abstract The production of T cell-activating factor(s) by macrophages stimulated with muramyl dipeptide (MDP) was studied. By MDP stimulation, a rapid increase in intracellular activity of the T cell-activating factor was induced, which preceded an increase of the activity in the extracellular medium. The rapid appearance of the activity in the cell and that in the medium were both inhibited by cycloheximide or puromycin. These results demonstrated that MDP stimulated rapid production of T cell-activating factors by inducing de novo synthesis of the factors, and that these newly formed factors are rapidly secreted. The activities of intracellular and extracellular secreted factors were both found in high m.w. (50,000 to 90,000) and low m.w. (10,000 to 30,000) fractions by gel filtration. The secreted high m.w. factor migrated as a single peak and did not dissociate into smaller components in SDS-PAGE analysis, indicating that the high m.w. factor is neither a complex of low m.w. factor with other proteins nor an aggregate of low m.w. factors. The properties are similar to those of our previously reported factor that helped antigenic activation of T cells for lymphokine production.</jats:p