Mechanism of peptide-induced mast cell degranulation: translocation and patch clamp studies.

Substance P and other polycationic peptides are thought to stimulate mast cell degranulation via direct activation of G proteins. We investigated the ability of extracellularly applied substance P to translocate into mast cells and the ability of intracellularly applied substance P to stimulate degranulation. In addition, we studied by reverse transcription--PCR whether substance P-specific receptors are present in the mast cell membrane. To study translocation, a biologically active and enzymatically stable fluorescent analogue of substance P was synthesized. A rapid, substance P receptor- and energy-independent uptake of this peptide into pertussis toxin-treated and -untreated mast cells was demonstrated using confocal laser scanning microscopy. The peptide was shown to localize preferentially on or inside the mast cell granules using electron microscopic autoradiography with 125I-labeled all-D substance P and 3H-labeled substance P. Cell membrane capacitance measurements using the patch-clamp technique demonstrated that intracellularly applied substance P induced calcium transients and activated mast cell exocytosis with a time delay that depended on peptide concentration (delay of 100-500 s at concentrations of substance P from 50 to 5 microM). Degranulation in response to intracellularly applied substance P was inhibited by GDPbetaS and pertussis toxin, suggesting that substance P acts via G protein activation. These results support the recently proposed model of a receptor-independent mechanism of peptide-induced mast cell degranulation, which assumes a direct interaction of peptides with G protein alpha subunits subsequent to their translocation across the plasma membrane

Penetration depth, multiband superconductivity, and absence of muon-induced perturbation in superconducting PrOs4_{4}Sb12_{12}

Transverse-field muon spin rotation ($\mu$SR) experiments in the heavy-fermion superconductor PrOs$_{4}$Sb$_{12}$ ($T_{c}=1.85$ K) suggest that the superconducting penetration depth $\lambda(T)$ is temperature-independent at low temperatures, consistent with a gapped quasiparticle excitation spectrum. In contrast, radiofrequency (rf) inductive measurements yield a stronger temperature dependence of $\lambda(T)$, indicative of point nodes in the gap. This discrepancy appears to be related to the multiband structure of PrOs$_{4}$Sb$_{12}$. Muon Knight shift measurements in PrOs$_{4}$Sb$_{12}$ suggest that the perturbing effect of the muon charge on the neighboring Pr$^{3+}$ crystalline electric field is negligibly small, and therefore is unlikely to cause the difference between the $\mu$SR and rf results.Comment: 10 pages, 7 figure

The composite picture of the charge carriers in La2-xSrxCuO4 (0.063 < x < 0.11) superconductors

Through far-infrared studies of La2-xSrxCuO4 single crystals for x = 0.063, 0.07, 0.09, and 0.11, we found that only ~ 0.2 % of the total holes participated in the nearly dissipationless normal state charge transport and superconductivity. We have also observed characteristic collective modes at w ~ 18 cm-1 and 22 cm-1 due to the bound carriers in an electronic lattice (EL) state and the free carriers are massively screened by the EL. Our findings lead us to propose a composite picture of the charge system where the free carriers are coupled to and riding on the EL. This unique composite system of charge carriers may provide further insights into the understanding of the cuprate physics.Comment: 10 pages, 4 figure

Unusual kondo behavior in the indium-rich heavy fermion antiferromagnet Ce3Pt4In13

We report the thermodynamic, magnetic, and electronic transport properties of the new ternary intermetallic system (Ce,La)3Pt4In13. Ce3Pt4In13 orders antiferromagnetically at 0.95 K while the non-magnetic compound La3Pt4In13 is a conventional 3.3 K superconductor. Kondo lattice effects appear to limit the entropy associated with the Neel transition to (1/4)Rln2 as an electronic contribution to the specific heat of gamma = 1 J/mole-Ce K2 is observed at TN; roughly 35% of this gamma survives the ordering transition. Hall effect, thermoelectric power, and ambient-pressure resistivity measurements confirm this interpretation. These results suggest that RKKY and Kondo interactions are closely balanced in this compound (TN = TK). Contrary to expectations based on the Doniach Kondo necklace model, applied hydrostatic pressure modestly enhances the magnetic ordering temperature with dTN/dP = +23 mK/kbar. As such Ce3Pt4In13 provides a counterexample to Kondo systems with similar Kondo and RKKY energy scales wherein applied pressure enhances TK at the expense of the ordered magnetic state.Comment: submitted to Physical Review

Optimal functional outcome measures for assessing treatment for Dupuytren's disease: A systematic review and recommendations for future practice

This article is available through the Brunel Open Access Publishing Fund. Copyright © 2013 Ball et al.; licensee BioMed Central Ltd.Background: Dupuytren's disease of the hand is a common condition affecting the palmar fascia, resulting in progressive flexion deformities of the digits and hence limitation of hand function. The optimal treatment remains unclear as outcomes studies have used a variety of measures for assessment. Methods: A literature search was performed for all publications describing surgical treatment, percutaneous needle aponeurotomy or collagenase injection for primary or recurrent Dupuytren’s disease where outcomes had been monitored using functional measures. Results: Ninety-one studies met the inclusion criteria. Twenty-two studies reported outcomes using patient reported outcome measures (PROMs) ranging from validated questionnaires to self-reported measures for return to work and self-rated disability. The Disability of Arm, Shoulder and Hand (DASH) score was the most utilised patient-reported function measure (n=11). Patient satisfaction was reported by eighteen studies but no single method was used consistently. Range of movement was the most frequent physical measure and was reported in all 91 studies. However, the methods of measurement and reporting varied, with seventeen different techniques being used. Other physical measures included grip and pinch strength and sensibility, again with variations in measurement protocols. The mean follow-up time ranged from 2 weeks to 17 years. Conclusions: There is little consistency in the reporting of outcomes for interventions in patients with Dupuytren’s disease, making it impossible to compare the efficacy of different treatment modalities. Although there are limitations to the existing generic patient reported outcomes measures, a combination of these together with a disease-specific questionnaire, and physical measures of active and passive individual joint Range of movement (ROM), grip and sensibility using standardised protocols should be used for future outcomes studies. As Dupuytren’s disease tends to recur following treatment as well as extend to involve other areas of the hand, follow-up times should be standardised and designed to capture both short and long term outcomes

Chest radiography practice in critically ill patients: a postal survey in the Netherlands

BACKGROUND: To ascertain current chest radiography practice in intensive care units (ICUs) in the Netherlands. METHODS: Postal survey: a questionnaire was sent to all ICUs with > 5 beds suitable for mechanical ventilation; pediatric ICUs were excluded. When an ICU performed daily-routine chest radiographs in any group of patients it was considered to be a "daily-routine chest radiography" ICU. RESULTS: From the number of ICUs responding, 63% practice a daily-routine strategy, in which chest radiographs are obtained on a daily basis without any specific reason. A daily-routine chest radiography strategy is practiced less frequently in university-affiliated ICUs (50%) as compared to other ICUs (68%), as well as in larger ICUs (> 20 beds, 50%) as compared to smaller ICUs (< 20 beds, 65%) (P > 0.05). Remarkably, physicians that practice a daily-routine strategy consider daily-routine radiographs helpful in guiding daily practice in less than 30% of all performed radiographs. Chest radiographs are considered essential for verification of the position of invasive devices (81%) and for diagnosing pneumothorax, pneumonia or acute respiratory distress syndrome (82%, 74% and 69%, respectively). On demand chest radiographs are obtained after introduction of thoracic drains, central venous lines and endotracheal tubes in 98%, 84% and 75% of responding ICUs, respectively. Chest films are also obtained in case of ventilatory deterioration (49% of responding ICUs), and after cardiopulmonary resuscitation (59%), tracheotomy (58%) and mini-tracheotomy (23%). CONCLUSION: There is notable lack of consensus on chest radiography practice in the Netherlands. This survey suggests that a large number of intensivists may doubt the value of daily-routine chest radiography, but still practice a daily-routine strategy

Low temperature thermal expansion of pure and inert gas-doped Fullerite C60

The low temperature (2-24 K) thermal expansion of pure (single crystal and polycrystalline) C60 and polycrystalline C60 intercalated with He, Ne, Ar, and Kr has been investigated using high-resolution capacitance dilatometer. The investigation of the time dependence of the sample length variations on heating shows that the thermal expansion is determined by the sum of positive and negative contributions, which have different relaxation times. The negative thermal expansion usually prevails at helium temperatures. The positive expansion is connected with the phonon thermalization of the system. The negative expansion is caused by reorientation of the C60 molecules. It is assumed that the reorientation is of quantum character. The inert gas impurities affect very strongly the reorientation of the C60 molecules especially at liquid helium temperatures. A temperature hysteresis of the thermal expansion coefficient of Kr- and He- C60 solutions has been revealed. The hysteresis is attributed to orientational polyamorphous transformation in these systems.Comment: 18 pages, 12 figure

On the polyamorphism of fullerite-based orientational glasses

The dilatometric investigation in the temperature range of 2-28K shows that a first-order polyamorphous transition occurs in the orientational glasses based on C60 doped with H2, D2 and Xe. A polyamorphous transition was also detected in C60 doped with Kr and He. It is observed that the hysteresis of thermal expansion caused by the polyamorphous transition (and, hence, the transition temperature) is essentially dependent on the type of doping gas. Both positive and negative contributions to the thermal expansion were observed in the low temperature phase of the glasses. The relaxation time of the negative contribution occurs to be much longer than that of the positive contribution. The positive contribution is found to be due to phonon and libron modes, whilst the negative contribution is attributed to tunneling states of the C60 molecules. The characteristic time of the phase transformation from the low-T phase to the high-T phase has been found for the C60-H2 system at 12K. A theoretical model is proposed to interpret these observed phenomena. The theoretical model proposed, includes a consideration of the nature of polyamorphism in glasses, as well as the thermodynamics and kinetics of the transition. A model of non-interacting tunneling states is used to explain the negative contribution to the thermal expansion. The experimental data obtained is considered within the framework of the theoretical model. From the theoretical model the order of magnitude of the polyamorphous transition temperature has been estimated. It is found that the late stage of the polyamorphous transformation is described well by the Kolmogorov law with an exponent of n=1. At this stage of the transformation, the two-dimensional phase boundary moves along the normal, and the nucleation is not important.Comment: 29 pages, 14 figures, added references, corrected typo