Rabbit cardiac and slow-twitch muscle express the same phospholamban gene

AbstractThe nucleotide sequences of cDNAs encoding phospholamban were found to be virtually identical when the cDNA clones were isolated from rabbit slow-twitch (soleus) and rabbit cardiac muscle libraries. These findings demonstrate that both types of muscle express the same phospholamban gene. The deduced amino acid sequences of rabbit and dog phospholamban were identical except for a change from Asp (dog) to Glu (rabbit) at position 2. The nucleotide sequences of the 5′- and the very long 3′-untranslated regions of rabbit and dog phospholamban cDNAs also exhibited a high percentage of identity

Characterization of anti-SARS-CoV-2 monoclonal antibodies focusing on antigen binding, neutralization, and FcγR activation via formation of immune complex

ABSTRACTSevere acute respiratory syndrome coronavirus 2 (SARS-CoV−2) causes coronavirus disease 2019 (COVID−19). Antibodies induced by SARS-CoV−2 infection or vaccination play pivotal roles in the body’s defense against the virus; many monoclonal antibodies (mAbs) against SARS-CoV−2 have been cloned, and some neutralizing mAbs have been used as therapeutic drugs. In this study, we prepared an antibody panel consisting of 31 clones of anti-SARS-CoV−2 mAbs and analyzed and compared their biological activities. The mAbs used in this study were classified into different binding classes based on their binding epitopes and showed binding to the SARS-CoV−2 spike protein in different binding kinetics. A multiplex assay using the spike proteins of Alpha, Beta, Gamma, Delta, and Omicron variants clearly showed the different effects of variant mutations on the binding and neutralization activities of different binding classes of mAbs. In addition, we evaluated Fcγ receptor (FcγR) activation by immune complexes consisting of anti-SARS-CoV−2 mAb and SARS-CoV−2 pseudo-typed virus, and revealed differences in the FcγR activation properties among the binding classes of anti-SARS-CoV−2 mAbs. It has been reported that FcγR-mediated immune-cell activation by immune complexes is involved in the promotion of immunopathology of COVID−19; therefore, differences in the FcγR-activation properties of anti-SARS-CoV−2 mAbs are among the most important characteristics when considering the clinical impacts of anti-SARS-CoV−2 mAbs

Importance of left ventricular minimal pressure as a determinant of transmitral flow velocity pattern in the presence of left ventricular systolic dysfunction

AbstractObjectives. This study was designed to assess whether the transmitral flow velocity pattern provides an estimation of left atrial pressure irrespective of the presence of left ventricular systolic dysfunction and, if not, to clarify the mechanism.Background. The pulsed Doppler transmitral flow velocity pattern, particularly peak early diastolic filling velocity, has been shown to change in parallel with left atrial pressure. However, extremely elevated left atrial pressure in association with heart failure does not necessarily cause an increase in peak early diastolic filling velocity in patients.Methods. Left atrial pressure was elevated with intravenous saline infusion in 11 dogs (normal left ventricular function group) and hemodynamic, transesophageal Doppler echocardiographic and M-mode echocardiographic variables were recorded at three different loading levels. In another 12 dogs, left atrial pressure was elevated by production of left ventricular systolic dysfunction with the stepwise injection of microspheres into the left coronary artery (left ventricular dysfunction group) and the same set of recordings was obtained at three different levels of dysfunction.Results. Peak early diastolic filling velocity increased with left atrial pressure in the normal left ventricular function group and correlated with mean left atrial pressure (r = 0.61, p < 0.01) and early diastolic left atrial to left ventricular crossover pressure (r = 0.71, p < 0.01). In contrast, peak early diastolic filling velocity did not increase with left atrial pressure in the left ventricular dysfunction grtup and did not correlate with mean left atrial pressure (r = −0.05) or the crossover pressure (r = 0.06). Peak early diastolic filling velocity correlated well with the difference between the crossover pressure and left ventricular minimal pressure in the left ventricular dysfunction group (r = 0.64, p < 0.01). In contract to peak early diastolic filling velocity, deceleration time of the early diastolic filling wave correlated with mean left atrial pressure and the crossover pressure irrespective of the primary cause of preload alteration (r = −0.54, r = −0.59, p < 0.01 respectively, n = 69 for all data).Conclusions. Preload dependency of the Doppler transmitral flow velocity pattern is hampered if an increase in left atrial pressure is due to left ventricular systolic dysfunction. In this setting, the increase in left ventricular minimal pressure due to left ventricular systolic dysfunction cancels the effect of the increase in left atrial pressure on the flow velocity pattern