Persistent atrial paralysis: Case report with light microscopy and ultrastructural analyses

Persistent atrial paralysis in a patient with complete heart block and mild mitral insufficiency is presented. Left atrial specimens obtained during implantation of a permanent cardiac pulse generator showed evidence of hypertrophy and fibrosis; subcellular degenerative changes ranged from near normal to irreversible, thus suggesting that atrial paralysis may be due to the replacement of normal atrial muscle with nonfunctional fibrous tissue.     

Ionescu-Shiley pericardial xenograft valve: Hemodynamic evaluation and early clinical follow-up of 326 patients

Dissatisfaction with the hemodynamic characteristics of available porcine valves prompted a clinical trial of the Ionescu-Shiley percardial xenograft (ISPX) valve. Three hundred fifty-six ISPX valves were implanted consecutively in 326 patients. Operative mortality was 2.6% (2/75) for aortic valve replacement alone and 7.7% (12/155) for aortic valve replacements that included reoperations and combined procedures such as mitral commissurotomy, annuloplasty, and coronary artery bypass. Operative mortality for all patients who underwent mitral valve replacement was 9.5% (14/147). The mean peak systolic gradient pressure in the aortic position was 5.4 mm Hg overall and 4.27 mm Hg with the size 19 mm valve. There were no embolic episodes in patients who received the ISPX valve in the aortic position. The available data indicate that the rate of peripheral embolism with the ISPX valve compares favorably with that of porcine valves. Considering its hemodynamic advantage, if the longterm durability of the full-orifice Ionescu-Shiley pericardial xenograft valve continues to be confirmed by follow-up studies, it is our opinion that it is the biologic valve of choice.     

SUCCESSFUL AORTOCORONARY BYPASS SURGERY IN A PATIENT WITH CLASSICAL HEMOPHILIA A

A patient with documented Factor VIII deficiency (classical Hemophilia A) and a history of previous severe intra- and postoperative hemorrhage and transfusion reaction underwent myocardial revascularization for advanced triple vessel coronary artery occlusive disease. The coagulation status was investigated, and a replacement regimen was instituted. The surgical procedure and postoperative course were uneventful.     

On the defence strategy of Physa fontinalis (L.), a freshwater pulmonate snail

Summary Physa fontinalis (L.) gives a characteristic, chemically mediated escape response when stimulated by the majority of British leeches and flatworms. The snail responds rapidly and consistently to contact with all the molluskivorous leeches but also to three species which may be considered harmless. However, no response was given to Erpobdella octoculata, the most abundant and widespread of the harmless leeches. The flatworms generally evoked less strong reactions. The adaptive significance of the pattern of responsiveness is discussed. A weaker shell-shaking response is elicited in conspecifics and it is shown that this antisocial behaviour leads to a relatively spaced-out dispersion pattern. A possible adaptive advantage is the reduction of risk of detection by shell-crushing fish predators, to which the snails are otherwise extremely vulnerable.     

Drosophila Kelch regulates actin organization via Src64-dependent tyrosine phosphorylation

The Drosophila kelch gene encodes a member of a protein superfamily defined by the presence of kelch repeats. In Drosophila, Kelch is required to maintain actin organization in ovarian ring canals. We set out to study the actin cross-linking activity of Kelch and how Kelch function is regulated. Biochemical studies using purified, recombinant Kelch protein showed that full-length Kelch bundles actin filaments, and kelch repeat 5 contains the actin binding site. Two-dimensional electrophoresis demonstrated that Kelch is tyrosine phosphorylated in a src64-dependent pathway. Site-directed mutagenesis determined that tyrosine residue 627 is phosphorylated. A Kelch mutant with tyrosine 627 changed to alanine (KelY627A) rescued the actin disorganization phenotype of kelch mutant ring canals, but failed to produce wild-type ring canals. Electron microscopy demonstrated that phosphorylation of Kelch is critical for the proper morphogenesis of actin during ring canal growth, and presence of the nonphosphorylatable KelY627A protein phenocopied src64 ring canals. KelY627A protein in ring canals also dramatically reduced the rate of actin monomer exchange. The phenotypes caused by src64 mutants and KelY627A expression suggest that a major function of Src64 signaling in the ring canal is the negative regulation of actin cross-linking by Kelch.     

Characterisation of an industrial affinity process used in the manufacturing of digoxin-specific polyclonal Fab fragments

This paper describes the effect of several variables on the affinity process for the production of the FDA approved biotherapeutic product Digoxin Immune Fab (Ovine) (DigiFab, Protherics Inc., TN, USA). The study considers the effects of column re-use on matrix capacity and on the subsequent recovery of the antibody product, and the impact of varying column loading on matrix performance. The methodology used could be equally applied to assess the feasibility of using an affinity matrix for commercial scale purification of alternative antibody derived biotherapeutics. The capacity and specific Fab recovery were calculated through 24h equilibrium and mass balance studies. Results were assessed against data obtained through confocal scanning laser microscopy. Scale-down experiments produced specific Fab recoveries and purities that were comparable with those at production scale. The matrix capacity was found to be 45+/-15 mg of Fab/ml of matrix. Through the use of fluorescent DigiFab and confocal scanning techniques, Fab uptake onto single affinity bead was evaluated. Average intensity values calculated for each sample provided direct real-time, measure of Fab binding and matrix capacity. The results suggest that the affinity matrix had a limited reuse life as a drop in recovery is observed following the completion of a small number of process cycles (30% after three runs). The findings support that which is seen at the current manufacturing scale, where the affinity column is used for a limited number of runs. Results from this study can be used as a basis for future optimisation of this purification process.