The Current Role of Surgery in the Treatment of Cardiac Metastases from Malignant Melanoma: an Educational Presentation.

A 71 year-old male with a history of multiple excisions of an initial Clark's level V melanoma of the breast followed by combined radiation and interferon treatment, as well as a recurrence, 3 years later, of a BRAF-positive tumor of the shoulder, with subsequent therapy with dabrafenib and trametinib, presented again with progressive intracardiac masses causing significant right ventricular outflow obstruction. Additionally, the patient complained of dyspnea and fatigue on exertion, thus he was scheduled for surgical resection.

A technique to resect the Edwards SAPIEN 3 Transcatheter Heart Valve 18 months after implantation in case of surgical aortic valve replacement.

Transcatheter aortic valve implantation (TAVI) evolved to an established treatment for meanwhile moderate-risk surgical patients suffering from severe aortic stenosis. Due to its less invasiveness, avoiding the use of cardiopulmonary bypass, the procedure demonstrated to be an efficient and safe treatment option. However, long-term results regarding these new valve prostheses are still lacking.

Cardiovascular magnetic resonance assessment of the aortic valve stenosis: an in vivo and ex vivo study.

Background: Aortic valve area (AVA) estimation in patients with aortic stenosis may be obtained using several methods. This study was undertaken to verify the cardiovascular magnetic resonance (CMR) planimetry of aortic stenosis by comparing the findings with invasive catheterization, transthoracic (TTE) as well as tranesophageal echocardiography (TEE) and anatomic CMR examination of autopsy specimens.

Methods: Our study was performed in eight patients with aortic valve stenosis.

Combination of the human prolyl isomerase FKBP12 with unrelated chaperone domains leads to chimeric folding enzymes with high activity.

Folding enzymes often use distinct domains for the binding of substrate proteins ("chaperone domains") and for the catalysis of slow folding reactions such as disulfide formation or prolyl isomerization. The human prolyl isomerase FKBP12 is a small single-domain protein without a chaperone domain. Its very low folding activity could previously be increased by inserting the chaperone domain from the homolog SlyD (sensitive-to-lysis protein D) of Escherichia coli.

A kinetic approach to determining the conformational stability of a protein that dimerizes after folding.

A strongly stabilized form of the β1 domain of the streptococcal protein G, termed Gβ1-M2, was previously obtained by an in vitro selection method for stabilized protein variants. It contains four substitutions, but how they contribute to the Gibbs free energy of denaturation (ΔG(D)) could not be determined, because, unlike the wild-type protein, Gβ1-M2 dimerizes in a spectroscopically silent reaction. Here we determined the ΔG(D) of the folded Gβ1-M2 monomer by using a kinetic approach that uncouples the folding of the monomer from dimerization.

Folding mechanism of an extremely thermostable (βα)(8)-barrel enzyme: a high kinetic barrier protects the protein from denaturation.

HisF, the cyclase subunit of imidazole glycerol phosphate synthase (ImGPS) from Thermotoga maritima, is an extremely thermostable (βα)(8)-barrel protein. We elucidated the unfolding and refolding mechanism of HisF. Its unfolding transition is reversible and adequately described by the two-state model, but 6 weeks is necessary to reach equilibrium (at 25 °C).

Influence of the stability of a fused protein and its distance to the amyloidogenic segment on fibril formation.

Conversion of native proteins into amyloid fibrils is irreversible and therefore it is difficult to study the interdependence of conformational stability and fibrillation by thermodynamic analyses. Here we approached this problem by fusing amyloidogenic poly-alanine segments derived from the N-terminal domain of the nuclear poly (A) binding protein PABPN1 with a well studied, reversibly unfolding protein, CspB from Bacillus subtilis. Earlier studies had indicated that CspB could maintain its folded structure in fibrils, when it was separated from the amyloidogenic segment by a long linker.

Semisynthesis of a homogeneous glycoprotein enzyme: ribonuclease C: part 2.

Active RNase glycoprotein from three pieces: The glycoprotein enzyme ribonuclease C, which contains a complex saccharide N-glycan, was synthesized by sequential native chemical ligation. An optimized ligation and isolation protocol allowed the efficient assembly and refolding of the 124 amino acid enzyme.

Semisynthesis of a homogeneous glycoprotein enzyme: ribonuclease C: part 1.

Seven in one blow: The efficient formation of mixed disulfides on the thiol-rich fusion protein A followed by subsequent intein cleavage gave the fragment B with all seven cysteines protected against oxidation. The native chemical ligation of B with synthetic glycopeptide thioesters provides glycoproteins.

Dilatation of the ascending aorta in bicuspid aortic valve disease: a magnetic resonance imaging study.

Background: Bicuspid aortic valve disease (BAV) is increasingly recognized as a disease of the entire proximal aorta including both valvular and vascular complications. The aim of our study was to assess the dimensions of the thoracic aorta using MRI in a broad spectrum of BAV and tricuspid aortic valve disease (TAV) and to define the prevalence of the dilatation of the ascending aorta (AA) >or= 4.5 cm in severe BAV disease.

Recellularization of biological heart valves with human vascular cells: in vitro hemocompatibility assessment.

Coverage of cardiovascular bioprostheses with autologous endothelium is used for the purpose of improving blood compatibility. The aim of our study was to analyze endothelialization potential of glutaraldehyde-fixed heart valves, cellular functions of seeded endothelial cells (EC), and the impact of a two-stage seeding protocol using human vascular fibroblasts (FB) and EC from saphenous veins (HSVEC) on cellular functional properties in vitro. Adherence and morphology of adhered cells were assessed by scanning electronic microscopy and immunohistochemistry.

A folded and functional protein domain in an amyloid-like fibril.

The effect of the polypeptide environment on polyalanine-induced fibril formation was investigated with amyloidogenic fragments from PAPBN1, a nuclear protein controlling polyadenylation. Mutation-caused extensions of the natural 10 alanine sequence up to maximally 17 alanines result in fibril formation of PABPN1 and the development of the disease oculopharyngeal muscular dystrophy (OPMD). We explored the influence of fibril formation on the structure and function of a one-domain protein linked to the fibril-forming part of PABPN1.

Bridge to lung transplantation through a pulmonary artery to left atrial oxygenator circuit.

Background: There is no mechanical device available to support patients with end-stage lung failure for weeks and months until appropriate donor organs for lung transplantation are available.

Methods: In a 38-year-old female patient with primary pulmonary hypertension a paracorporeal artificial lung (PAL) system was placed parallel to the pulmonary circulation with connections to the pulmonary artery and to the left atrium. The key component of the PAL was a low-resistance membrane oxygenator.

Influence of inflow cannula length in axial-flow pumps on neurologic adverse event rate: results from a multi-center analysis.

Background: The application of axial-flow pumps in patients with end-stage heart failure reveals a significantly reduced infectious complication rate as compared with rates observed with pulsatile devices. The remaining adverse event rate relates mainly to thromboembolic complications with neurologic consequences. We investigated the dependence of the neurologic adverse event rate on the length of the inflow cannula.

Chaperone-aided in vitro renaturation of an engineered E1 envelope protein for detection of anti-Rubella virus IgG antibodies.

The envelope glycoproteins of Rubella virus, E1 and E2, mediate cell tropism, and E1 in particular plays a pivotal role in the fusion of the virus with the endosomal membrane. Both are the prime targets of the humoral immune response. Recombinant variants of the E1 ectodomain as well as E1 antigen preparations from virus lysates are commonly used to detect anti-Rubella immunoglobulins in human sera.

Inhibition of thrombocyte aggregation during extracorporeal lung assist: a case report.

In extracorporeal lung assist, membrane oxygenators are used to improve gas exchange. Accumulations on the membranes of coagulation end products can increase resistance to blood flow and diffusion distance. Thus, functioning of the system can be impaired and, in extreme cases, lead to malfunction which may necessitate change out of the oxygenator.

Advantages of human umbilical vein scaffolds derived from cesarean section vs. vaginal delivery for vascular tissue engineering.

The current study investigated whether the mode of delivery and the mode of sample collection affect the functional properties of umbilical veins as scaffolds for vascular tissue engineering purposes. Human umbilical vein (HUV) from planned cesarean-sections (PCS) showed a 1.7-fold higher maximum contraction with potassium chloride compared to spontaneous vaginal deliveries (VDs, p=0.

From Baghdad to Germany: use of a new pumpless extracorporeal lung assist system in two severely injured US soldiers.

The authors describe a new extracorporeal pumpless interventional lung assist system (iLA) that was implemented in two US soldiers with severe acute respiratory distress syndrome received from enemy action in Iraq, who were at risk for critical hypoxemia/hypercapnia. The system is characterized by a new low-resistance gas exchange membrane that is integrated in an arterial-venous bypass established by cannulation of the femoral artery and vein. Cardiovascular stability is essential to produce sufficiently high blood flow rates over the gas exchange unit.

Direct evidence of endothelial injury during cardiopulmonary bypass by demonstration of circulating endothelial cells.

Endothelial activation is considered a key process in the development of a whole body inflammatory response secondary to cardiopulmonary bypass (CPB). Increased levels of a multitude of soluble mediators have been described as being released during and after cardiac surgery. Circulating endothelial cells have recently been established as a novel marker of endothelial damage in a variety of vascular disorders.

A new pumpless extracorporeal interventional lung assist in critical hypoxemia/hypercapnia.

Objective: Pump-driven extracorporeal gas exchange systems have been advocated in patients suffering from severe acute respiratory distress syndrome who are at risk for life-threatening hypoxemia and/or hypercapnia. This requires extended technical and staff support.

Design: We report retrospectively our experience with a new pumpless extracorporeal interventional lung assist (iLA) establishing an arteriovenous shunt as the driving pressure.

Endothelial apoptosis and circulating endothelial cells after bypass grafting with and without cardiopulmonary bypass.

Objective: We compared profiles of the numbers of circulating endothelial cells (CEC) and the apoptosis-inducing capacity of serum samples on human endothelial cells (hEC) in on-pump and off-pump coronary artery bypass grafting (CABG) patients.

Methods: Blood samples from 30 patients undergoing CABG (randomly assigned to two groups: 15 patients off-pump and 15 on-pump (cardiopulmonary bypass, CPB)) were collected after induction of anesthesia (preoperatively), at weaning from CPB/end of bypass grafting (0 h), and 1, 6, 12, 24, and 48 h afterwards. CEC were isolated with immunomagnetic anti-CD146-coated Dynabeads, and counted in a Nageotte chamber.

SlyD proteins from different species exhibit high prolyl isomerase and chaperone activities.

SlyD is a putative folding helper protein from the Escherichia coli cytosol, which consists of an N-terminal prolyl isomerase domain of the FKBP type and a presumably unstructured C-terminal tail. We produced truncated versions without this tail (SlyD) for SlyD from E. coli, as well as for the SlyD orthologues from Yersinia pestis, Treponema pallidum, Pasteurella multocida, and Vibrio cholerae.