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In two consecutive papers we study the stability of black lipid films against thermally induced hydrodynamic fluctuations. In the present part we develop a semiphenomenological theory of steric repulsion in these films. The model employs the statistical mechanical formulation of the van der Waals theory of simple liquid–vapor interfaces; it is based on the picture that upon diminishing the film thickness the adjacent interfacial layers start overlapping in the film center raising the degree of orientation of the hydrocarbon segments there. This causes a mutual repulsion of the two film surfaces. The general order parameter profile is found to depend on two parameters which can be determined from film compression measurements. [ABSTRACT FROM AUTHOR]

We investigate the impact of the steric force (modeled in part I) on the linear dynamics of a thin lipid film with plane parallel surfaces at rest. We perform a stability analysis of the hydrodynamic fluctuations of the film, exposed to an external electric field. For long wavelengths, we find the stability of the film against bending to be governed by the total film tension. Stability against periodic thickness fluctuations (squeezing) is determined by the film elasticity. In both cases, sterics counteracts the destabilizing action of the van der Waals and electrostatic forces. We establish a diagram which displays the regimes of film stability as a function of film thickness and electric cross film potential. The film is predicted to be stable against squeezing for film thickness smaller than a critical film thickness (of the order of 60 Å). The latter depends slightly on the applied voltage. Voltages larger than 190 mV trigger bending of low tension films (single interface tension: 0.05 dyn/cm) above and just below the critical squeezing thickness. For these voltages, bending of the film is prevented only by reducing the film thickness. [ABSTRACT FROM AUTHOR]

The MYB oncogene is a leucine zipper transcription factor essential for normal and malignant hematopoiesis. In T-cell acute lymphoblastic leukemia (T-ALL), elevated MYB levels can arise directly through T-cell receptor-mediated MYB translocations, genomic MYB duplications or enhanced TAL1 complex binding at the MYB locus or indirectly through the TAL1/miR-223/FBXW7 regulatory axis. In this study, we used an unbiased MYB 3′untranslated region-microRNA (miRNA) library screen and identified 33 putative MYB-targeting miRNAs. Subsequently, transcriptome data from two independent T-ALL cohorts and different subsets of normal T-cells were used to select miRNAs with relevance in the context of normal and malignant T-cell transformation. Hereby, miR-193b-3p was identified as a novel bona fide tumor-suppressor miRNA that targets MYB during malignant T-cell transformation thereby offering an entry point for efficient MYB targeting-oriented therapies for human T-ALL. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in which targeted mutational profiling of peripheral T-cell lymphoma not otherwise specified highlighting new mechanisms in a heterogeneous pathogenesis is being discussed.

Background. Expression of p16 is a marker for human papillomavirus (HPV)-related carcinogenesis in head and neck cancer. The purpose of this study is to determine if p16 immunoreactivity is associated with aberrant expression of components of the PI3 kinase pathway. Methods. A tissue microarray (TMA) was constructed for 46 archived tonsillar squamous cell carcinoma specimens. Clinical demographics of these patients were analyzed, and the TMA was interrogated with antibodies directed against p16, phosphorylated AktSer473, phosphorylated S6Ser240/244, phosphorylated S6Ser235/236, phosphorylated 4E-BP1Thr37/46, phosphorylated eIF4ESer209, PTEN, p21, and p53. Results. There was a significant correlation between history of tobacco abuse (>10 pack/years) and absence of p16 expression ( p = .01). Expression of p16 was significantly associated with immunoreactivity of p21 ( p = .02), PTEN ( p = .02), and phosphorylated eIF4E ( p = .03). There was no evidence of association between p16 status and expression of phosphorylated S6, phosphorylated 4E-BP1, or p53. Conclusion. p16 positive tonsillar squamous cell carcinoma is characterized by expression of phosphorylated eIF4E that may occur via a mammalian target of rapamycin (mTOR)-independent mechanism. © 2010 Wiley Periodicals, Inc. Head Neck, 2010 [ABSTRACT FROM AUTHOR]

Background: Acute rejection reactions and the development of graft arterial disease are serious limitations after transplantation. Both are connected to the expression of adhesion molecules on the activated microvascular endothelium of the allograft. Methods: siRNA-mediated silencing of ESELE, ICAM-1, and VCAM-1 on human cardiacmicrovascular cells (HCMEC) was investigated in order to inhibit leukocyte-endothelial interactions. HCMEC were investigated for the time-dependent expression of ESELE, ICAM-1, and VCAM-1 after TNF-a stimulation and for siRNA mediated suppression using a nonviral transfecting approach. Furthermore, the effects of siRNA transfection on leukocyte binding to the endotheliumwere analyzed. Results: Transfection with siRNA induced a significant suppression of adhesion molecule expression, regardless of whether there had been a prior single or cocktail transfection of the sequences (p < 0.05). The quantity of attaching leukocytes was significantly reduced after an equal silencing of adhesion molecules (p < 0.05). Conclusions: This investigation demonstrates that liposomal transfection of HCMEC with specific siRNA sequences is capable of both repressing adhesion molecule expression and of reducing subsequent leukocyte-endothelial actions. [ABSTRACT FROM AUTHOR]

Objectives: Hydrotin-C is a bacterial cellulose consisting of 90% of physiological solution. The cellulose pad is smooth and elastic and cannot be torn, and is therefore suitable for use on any local skin condition. The aim of this study was to evaluate the image quality (IQ) and transducer pressure of Hydrotin-C-Pads as a solid coupling agent compared with standard coupling gel. Methods: To date, transthoracic echocardiography has been performed in 51 patients (ongoing study) using standard coupling gel and Hydrotin-C-Pads. The IQ was categorized as follows: 1 = excellent, 2 = good, 3 = poor, 4 = inadequate. All patients were questioned about the transducer pressure, which was categorized as: 0 = less, 1 = equal, 2 = more. The body mass index (BMI) was documented for all patients. Results: The IQ was very good with Hydrotin-C-Pads. The IQ was better in 84% of all patients. In patients with a BMI of over 25 and in patients with a BMI of over 30, Hydrotin-C-Pads was also better compared with standard gel. The transducer pressure was lower in 33 patients. Conclusions: Hydrotin-C-Pads can be used as a solid ultrasonic coupling agent. Because of the consistent thickness of the coupling zone, the IQ seems to be better for Hydrotin-C-Pads compared with standard coupling gel. The transducer presser is lower, and these pads are easy to apply and are reusable and reduce the burden of clean-up after treatment. [ABSTRACT FROM AUTHOR]

Myelosuppression is the most common unwanted side effect associated with the administration of anticancer drugs, and infections remain a common cause of death in chemotherapy-treated patients. Several mechanisms of the cytotoxicity of these drugs have been proposed and may synergistically operate in a given cell. Survivin expression has been associated with cancer, but recent reports suggest that this molecule is also expressed in several immature and mature hematopoietic cells. Here, we provide evidence that treatment of immature neutrophils with anticancer drugs reduced endogenous survivin levels causing apoptosis. The anticancer drugs did not directly target survivin, instead they blocked the activity of phosphatidylinositol-3-OH kinase, which regulated survivin expression and apoptosis in these cells. Strikingly, and in contrast to other cells, this pathway did not involve the serine/threonine kinase c-akt/PKB. Moreover, in combination with anticancer drug therapy, rapamycin did not induce increased myelosuppression in an experimental lymphoma mouse model. These data suggest that drugs that block either c-akt/PKB or signaling molecules located distal to c-akt/PKB may preferentially induce apoptosis of cancer cells as they exhibit no cytotoxicity for immature neutrophils.Oncogene (2006) 25, 6915–6923. doi:10.1038/sj.onc.1209692; published online 22 May 2006 [ABSTRACT FROM AUTHOR]

The flexed-arm hang (FAH) has been used to assess arm and shoulder girdle strength for 35 years despite little evidence to support its use. The purpose of this study was to determine what muscular fitness component, if any, was related to the FAH. The traditional overgrip chin-above-bar test and 5 different variations were compared with absolute strength (1 repetition maximum [1RM] lat pull down), relative strength (1RM·mass-1), and muscle endurance (repetitions to failure at 70% of the 1RM). Sixty college-age women volunteered for the study. Relationships were examined using Pearson Product Moment Correlation. No significant relationship was found between any of the FAH variations and absolute strength or muscle endurance; however, all FAH variations correlated significantly with relative strength (1RM·mass-1). The strongest relationship was with the undergrip FAH timed to 908 of elbow extension (r = 0.72). Investigators concluded that the FAH is a test of weight-relative muscular strength and appears unrelated to absolute strength or muscle endurance. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To evaluate a new Doppler echocardiographic index of obstruction in patients with native coarctation or recoarctation. PATIENTS--32 patients (mean age 20, range 3 months--50 years). METHODS--Magnetic resonance imaging (MRI) was used to investigate the descending aorta. The cross sectional area of the obstruction was compared with the area of the abdominal aorta as an index of obstruction (CoA index). Doppler echocardiography was used to record the velocities in the coarctation jet and in the abdominal aorta. According to the continuity equation the ratio of these velocities should equal the ratios of the cross sectional areas. The gradients and diastolic half time of the Doppler curve were calculated. RESULTS--There was a close correlation between the MRI index of obstruction and the Doppler velocity ratio (r = 0.92). The sensitivity and specificity of this ratio in detecting a CoA index equal to or less than 0.25 were better than those obtained with gradients only or the combination of gradients and diastolic half time. CONCLUSION--The new Doppler velocity ratio correlated closely with an anatomical index of obstruction. It was easy to record in most patients and it avoided difficulties about the choice of instantaneous or peak to peak gradients and whether or not to subtract proximal velocities for the calculation of gradients. [ABSTRACT FROM PUBLISHER]

Recently, we have developed an analytical, semi-microscopic theory for the macroscopic behavior of a solvent-containing black lipid film subjected to an electric cross film voltage, Δ. Here we employ the theoretical expressions derived for the disjoining pressure, П, the film elasticity, ε, and the film tension, γ, to construct the stability diagram of the film, in the П-Δ. Depending on its state (П, Δ), the film is stable or is prone to squeezing or bending deformations. For a monooleate film we show how the destruction of the plane film due to a periodic thickness fluctuation (squeezing) is facilitated by two mechanisms: i) lowering of П at fixed Δ; ii) lowering of Δ at fixed П, provided that the film is in a stable state characterized by П<−7.03×10 dyne/cm and Δ>0 mV. Bending of a low tension film (single interface tension γ ∼ 0.025 dyne/cm) can be achieved only for Δ>170 mV and П > −8.7 × 10 dyne/cm. Finally, we demonstrate the existence of a marginal state (П, Δ) where the film is predicted to exhibit strong fluctuations both in the squeezing and in the bending mode. [ABSTRACT FROM AUTHOR]

We introduce a general hydrodynamic model to study the stability of lipid films against thermal fluctuations. As one novel aspect the model accounts before all for a complete intrinsic surface rheology of the film interfaces. Thus the rheological behaviour of the surface adsorbed lipids is modelled which screen the hydrophobic film interior against the aqueous exterior. For coloured films we demonstrate first the influence of electrical forces on the dynamics and film stability. For that we perform a linear stability analysis on a simplified mechanically symmetric film with i) symmetric surface charge distribution and ii) linear electric potential drop across the film. Based on the complete film model we then categorize the complete set of solutions of the linearized equations of motion and we study the growth rates of unstable film modes. Finally we discuss the stability properties of a black film after introducing a repulsive mechanism due to the steric hindrance of the interfacial lipids. [ABSTRACT FROM AUTHOR]

Meropenem and imipenem/cilastatin were compared in an open, randomised prospective multicentre study in the treatment of acute exacerbations of severe chronic obstructive pulmonary disease in hospitalised patients. One-hundred-and-seventy-three patients were enrolled; 164 were evaluable for clinical efficacy and 98 for bacteriological efficacy, with 144 pathogens isolated. The predominant pathogens were Haemophilus influenzae (n = 30), Streptococcus pneumoniae (18), Staphylococcus aureus (12), Pseudomonas aeruginosa (11), Moraxella catarrhalis(8), other Gram-negative bacteria (Neisseria, Klebsiella, Proteus, and Enterobacter spp.) (53) and other Gram-positive bacteria (12). A single bacterial pathogen was identified in 61 patients, whereas two bacterial pathogens were isolated in 31 patients and three in six patients. The clinical response at the end of treatment was very high in both groups with a satisfactory outcome (cured or improved) in 97.6% of the meropenem patients and in 96.3% of the imipenem/cilastatin patients; at follow-up the rates were 89.1% and 89.8%, respectively. The bacterial success (eradication or presumed eradication) was 88.2% in the meropenem group and 89.4% in the comparator group. Nausea or vomiting were reported more frequently in patients treated with imipenem/cilastatin, whereas in the meropenem group an increase in aminotransferases was reported. One patient treated with imipenem/cilastatin was withdrawn from the study due to seizures. Meropenem and imipenem/cilastatin were highly effective for the treatment of severe bacterial exacerbations of chronic bronchitis but meropenem was better tolerated. [ABSTRACT FROM PUBLISHER]

Dobrava virus infection was diagnosed serologically by enzyme-linked immunosorbent and immunofluorescence assays. To determine which hantavirus serotype was involved, sera were analyzed by a focus reduction neutralization test. The clinical data indicated that only pulmonary manifestation was present. Our data support the presence of Dobrava virus infection outside the Balkan region. In conclusion, a previously healthy adult with unexplained pulmonary perfusion failure should be investigated for hantavirus infection. [ABSTRACT FROM AUTHOR]

In patients with suspected recoarctation of the aorta the estimation of the pressure difference between the arms and legs is an important part of the examination. Because this difference is often augmented when the circulation is stressed by exercise, exercise tests are a useful part of the evaluation. Doppler echocardiography was used to estimate this pressure difference in 16 adult patients in whom simultaneous pressure and Doppler recordings were made both at rest and during exercise. There was a close correlation between the invasive peak instantaneous gradient and the Doppler gradient both at rest and during exercise. There was only a moderate correlation between the invasive peak to peak gradient and the Doppler gradient at rest and during exercise. Doppler echocardiography is recommended as an easy and accurate method of estimating the peak instantaneous gradient both at rest and during exercise in patients with suspected recoarctation. [ABSTRACT FROM PUBLISHER]

The reptation model is generalized on the basis of a theory which accounts for hindered defect diffusion along the chain. A basic ingredient of the theory is a waiting time distribution for the hops of elementary defects which store length. Important rheological quantities are found to generally depend on fractional powers of the molecular mass rather than on integer powers as in the conventional reptation picture. Ein verallgemeinertes Reptationsmodell wird vorgestellt. Entlang einer Polymerkette berücksichtigt es die gehinderte Difussion von Defekten, die Länge speichern. Dieser Effekt wird beschrieben mittels einer Wartezeitverteilung für die Defektplatzwechselvorgänge. In der Folge findet man für wichtige rheologische Größen Molekulargewichtsabhängigkeiten in Form von Potenzgesetzen mit gebrochenen Exponenten an Stelle der ganzzahligen Exponenten des konventionellen Reptationsmodells. [ABSTRACT FROM AUTHOR]

Following percutaneous coronary intervention, vascular closure devices (VCDs) are increasingly used to reduce time to ambulation, enhance patient comfort, and reduce potential complications compared with traditional manual compression. Newer techniques include complicated, more or less automated suture devices, local application of pads or the use of metal clips and staples. These techniques often have the disadvantage of being time consuming, expensive or not efficient enough. The VCD failure rate in association with vascular complications of 2.0-9.5%, depending on the type of VCD, is still not acceptable. Therefore, the aim of this study is to develop a self-expanding quick vascular closure device (QVCD) made from a bioabsorbable elastic polymer that can be easily applied through the placed introducer sheath. Bioabsorbable block-co-polymers were synthesized and the chemical and mechanical degradation were determined by in vitro tests. The best fitting polymer was selected for further investigation and for microinjection moulding. After comprehensive haemocompatibility analyses in vitro, QVCDs were implanted in arterial vessels following arteriotomy for different time points in sheep to investigate the healing process. The in vivo tests proved that the new QVCD can be safely placed in the arteriotomy hole through the existing sheath instantly sealing the vessel. The degradation time of 14 days found in vitro was sufficient for vessel healing. After 4 weeks, the remaining QVCD material was covered by neointima. Overall, our experiments showed the safety and feasibility of applying this novel QVCD through an existing arterial sheath and hence encourage future work with larger calibers. [ABSTRACT FROM AUTHOR]