MxA Gene Expression after Live Virus Vaccination: A Sensitive Marker for Endogenous Type I Interferon

MxA gene expression is known to be regulated tightly and exclusively by type I interferons (IFNs). The kinetics of MxA gene expression was analyzed in peripheral blood mononuclear cells from 11 healthy volunteers vaccinated with the 17-D strain of yellow fever virus. A reliable induction of MxA RNA and MxA protein was found in the absence of easily detectable serum IFN activity. Thus, steady-state MxA RNA levels were elevated 8- to 30-fold above prevaccination levels on day 5 after vaccination. The average increase of MxA protein was ∼50-fold. In contrast, no induction of MxA RNA or MxA protein was detectable in 3 similarly vaccinated controls who were immune because of previous vaccinations. The IFN marker 2′-5′-oligoadenylate (2-5A) synthetase known to react to both type I and type II IFNs showed a similar response but did not differentiate equally well between nonimmune and immune vaccinees. β2-microglobulin and neopterin reacted poorly, remaining at low levels within the normal range. These results demonstrate that MxA gene expression is a good marker for detecting minute quantities of biologically active type I IFN during viral infection

CMS Barrel Pixel Detector Overview

The pixel detector is the innermost tracking device of the CMS experiment at the LHC. It is built from two independent sub devices, the pixel barrel and the end disks. The barrel consists of three concentric layers around the beam pipe with mean radii of 4.4, 7.3 and 10.2 cm. There are two end disks on each side of the interaction point at 34.5 cm and 46.5 cm. This article gives an overview of the pixel barrel detector, its mechanical support structure, electronics components, services and its expected performance.Comment: Proceedings of Vertex06, 15th International Workshop on Vertex Detector

Routine use of self-expanding venous cannulas for cardiopulmonary bypass: benefits and pitfalls in 100 consecutive cases

Objective: Assess the performance of self-expanding venous cannulas for routine use in open-heart surgery. Methods: Prospective study in 100 unselected consecutive patients undergoing open-heart surgery with either remote or central smart venous cannulation. Results: The study focuses on the 76 consecutive adult patients (mean age 59.2±17.3 years; 60 males, 16 females) undergoing surgical procedures with total cardiopulmonary bypass for either valve procedures (42/76 patients=55.3%), ascending aorta and arch repair (20/76 patients=26.3%), coronary artery revascularization (13/76 patients=17.1%) or other procedures (11/76 patients=14.5%) with 14/76 patients (18.4%) undergoing redo surgery and 6/76 patients (7.9%) undergoing small access surgery. The mean pump flow achieved by gravity drainage alone accounted for 5.0±0.6l/min (=114% of target) in the entire study population (n=76) as compared to the calculated, theoretical pump flow of 4.4±0.5l/min (p<0.0001). For the femoral cannulation sub-group (n=35) pump flow achieved by gravity drainage alone accounted for 4.9±0.6l/min (=114% of target) as compared to the calculated theoretical pump flow of 4.3±0.4l/min (p<0.0001). The corresponding numbers for trans-subclavian cannulation (n=7) are 5.2±0.5l/min (111%) for the pump flow achieved by gravity drainage as compared to the theoretical target flow of 4.7±0.4l/min. For the central cannulation sub-group (n=34) mean flow achieved by gravity drainage with a self-expanding venous cannula accounted for 5.1±0.7l/min (=116% of target) as compared to the calculated theoretical flow of 4.4±0.6l/min (p<0.0001). Conclusion: Full or more than target flow was achieved in 97% of the patients studied undergoing CPB with self-expanding venous cannulas and gravity drainage. Remote venous cannulation with self-expanding cannulas provides similar flows as central cannulation. Augmentation of venous return is no longer necessar

Role of homologous ASP334 and GLU319 in human non-gastric H,K- and Na,K-ATPases in cardiac glycoside binding

Cardiac steroids inhibit Na,K-ATPase and the related non-gastric H,K-ATPase, while they do not interact with gastric H,K-ATPase. Introducing an arginine, the residue present in the gastric H,K-ATPase, in the second extracellular loop at the corresponding position 334 in the human non-gastric H,K-ATPase (D334R mutation) rendered it completely resistant to 2mM ouabain. The corresponding mutation (E319R) in alpha1 Na,K-ATPase produced a approximately 2-fold increase of the ouabain IC(50) in the ouabain-resistant rat alpha1 Na,K-ATPase and a large decrease of the ouabain affinity of human alpha1 Na,K-ATPase, on the other hand this mutation had no effect on the affinity for the aglycone ouabagenin. These results provide a strong support for the orientation of ouabain in its biding site with its sugar moiety interacting directly with the second extracellular loop

Superior flow for bridge to life with self-expanding venous cannulas

Background: Recently, a compact cardiopulmonary support (CPS) system designed for quick set-up for example, during emergency cannulation, has been introduced. Traditional rectilinear percutaneous cannulas are standard for remote vascular access with the original design. The present study was designed to assess the potential of performance increase by the introduction of next-generation, self-expanding venous cannulas, which can take advantage of the luminal width of the venous vasculature despite a relatively small access orifice. Methods: Veno-arterial bypass was established in three bovine experiments (69 ± 10 kg). The Lifebridge® (Lifebridge GmbH, Munich, Germany) system was connected to the right atrium in a trans-jugular fashion with various venous cannulas; and the oxygenated blood was returned through the carotid artery with a 17 F percutaneous cannula. Two different venous cannulas were studied, and the correlation between the centrifugal pump speed (1500-3900 RPM), flow and the required negative pressure on the venous side was established: (A) Biomedicus 19 F (Medtronic, Tolochenaz, Switzerland); (B) Smart canula 18 F/36 F (Smartcanula LLC, Lausanne, Switzerland). Results: At 1500 RPM, the blood flow was 0.44 ± 0.26 l min−1 for the 19 F rectilinear cannula versus 0.73 ± 0.34 l min−1 for the 18/36 F self-expanding cannula. At 2500 RPM the blood flow was 1.63 ± 0.62 l min−1 for the 19 F rectilinear cannula versus 2.13 ± 0.34 l min−1 for the 18/36 F self-expanding cannula. At 3500 RPM, the blood flow was 2.78 ± 0.47 l min−1 for the 19 F rectilinear cannula versus 3.64 ± 0.39 l min−1 for the 18/36 F self-expanding cannula (p ≪ 0.01 for 18/36 F vs 19 F). At 1500 RPM, the venous line pressure was 18 ± 8 mmHg for the 19 F rectilinear cannula versus 19 ± 5 mmHg for the 18/36 F self-expanding cannula. At 2500 RPM the venous line pressure accounted for −22 ± 32 mmHg for the 19 F rectilinear cannula versus 2 ± 5 mmHg for the 18/36 F self-expanding cannula. At 3500 RPM, the venous line pressure was −112 ± 42 mmHg for the rectilinear cannula versus 28 ± 7 mmHg for the 18/36 F self-expanding cannula (p ≪ 0.01 for 18 F/36 F vs 19 F). Conclusions: The negative pressure required to achieve adequate venous drainage with the self-expanding venous cannula accounts for approximately 31% of the pressure necessary with the 19 F rectilinear cannula. In addition, a pump flow of more than 4 l min−1 can be achieved with the self-expanding design and a well-accepted negative inlet pressure for minimal blood trauma of less than 50 mmH

The third sodium binding site of Na,K-ATPase is functionally linked to acidic pH-activated inward current

Sodium- and potassium-activated adenosine triphosphatases (Na,K-ATPase) is the ubiquitous active transport system that maintains the Na(+) and K(+) gradients across the plasma membrane by exchanging three intracellular Na(+) ions against two extracellular K(+) ions. In addition to the two cation binding sites homologous to the calcium site of sarcoplasmic and endoplasmic reticulum calcium ATPase and which are alternatively occupied by Na(+) and K(+) ions, a third Na(+)-specific site is located close to transmembrane domains 5, 6 and 9, and mutations close to this site induce marked alterations of the voltage-dependent release of Na(+) to the extracellular side. In the absence of extracellular Na(+) and K(+), Na,K-ATPase carries an acidic pH-activated, ouabain-sensitive "leak" current. We investigated the relationship between the third Na(+) binding site and the pH-activated current. The decrease (in E961A, T814A and Y778F mutants) or the increase (in G813A mutant) of the voltage-dependent extracellular Na(+) affinity was paralleled by a decrease or an increase in the pH-activated current, respectively. Moreover, replacing E961 with oxygen-containing side chain residues such as glutamine or aspartate had little effect on the voltage-dependent affinity for extracellular Na(+) and produced only small effects on the pH-activated current. Our results suggest that extracellular protons and Na(+) ions share a high field access channel between the extracellular solution and the third Na(+) binding site

Augmented venous return for minimally invasive open heart surgery with selective caval cannulation

Objective: Minimally invasive open heart surgery involves limited intrathoracic cannulation sites necessitating cardiopulmonary bypass to be initiated via peripheral access using percutaneous cannulae with the tip placed into the right atrial cavity. However, surgery involving the opening of the right heart obliges the surgeon to maintain the end of the cannulae into the vena cavae. The impeded venous return due to the smaller diameter may be alleviated by inserting a centrifugal pump in the venous line. Methods: Right anterior mini-thoracotomy and exposure of the femoral site were performed before the patient was heparinized. Cannulation of the femoral artery, the inferior vena cava via the femoral vein and the superior vena cava through the mini-thoracotomy was performed and cardiopulmonary bypass was initiated. Venous drainage was augmented with the centrifugal pump. Cardiac arrest was provoked and both vena cavae were snared before performing the intracardiac procedure. Results: Twenty consecutive patients were operated on using this technique (15 males/five females; age: 44.8±14.3 years; bodyweight: 73.5±15.1 kg; body surface area: 1.8±0.2 m2; theoretical blood flow rate: 4.4±0.5 l/min). The cannula sizes were 21.9±2.2 Fr for the femoral artery, 26.5±1.7 Fr for the inferior vena cava and 23.8±2.5 Fr for the superior vena cava. Venous drainage through the single inferior vena cava cannula was 2.1±0.6 l/min (48.8±13.3% of the theoretical flow). Adding the superior vena cava cannula increased the venous flow to 3.1±0.4 l/min (70.7±9.6% of the theoretical value, P<0.005). The use of the centrifugal pump increased the flow to 4.1±0.6 l/min (93.4±8.9% of the theoretical flow, P<0.001) with a mean inlet negative pressure of −69.1±10.2 mmHg. The mean bypass time was 64.0±24.6 min for a mean operative time of 226.3±61.0 min. Minimum venous saturation was 69.4±8.5%. Conclusions: Despite the smaller diameter of the vena cavae compared to the right atrium, and a smaller internal diameter of percutaneous cardiopulmonary bypass cannulae compared to classic ones; the centrifugal pump improves the venous drainage significantly so that minimally invasive open heart procedures can be performed under optimal and safe perfusion condition