Cytokine profiles of stimulated blood lymphocytes in asthmatic and healthy adolescents across the school year

T cell cytokines play an important role in mediating airway inflammation in asthma. The predominance of a Th2 cytokine profile, particularly interleukin (IL)-4 and IL-5, is associated with the pathogenesis and course of asthma. The aim of this study was to test the hypothesis that a stressful life event alters the pattern of cytokine release in asthmatic individuals. Thirteen healthy controls and 21 asthmatic adolescents gave blood samples three times over a semester: midsemester, during the week of final examinations, and 2-3 weeks after examinations. Interferon-gamma (IFN-gamma), IL-2, IL-4, and IL-5 were measured from supernatants of cells stimulated with PHA/PMA for 24 h. Cells from asthmatic subjects released significantly more IL-5 during the examination and postexamination periods, whereas cells from healthy controls released significantly more IL-2 during the midsemester and examination periods, thereby indicating a bias for a Th2-like pattern in asthmatics and a Th1-like pattern in healthy controls. IL-4 and IL-5 production showed a marked decrease during and after examinations in healthy controls, whereas this decline was absent in asthmatics. The ratios of IFN-gamma:IL-4 and IFN-gamma:IL-5 also revealed significant changes in the profile of cytokine release across the semester. These results indicate differential cytokine responses in asthmatics that may become pronounced during periods of cellular activation.     

Preferential exclusion of sucrose from recombinant interleukin-1 receptor antagonist: role in restricted conformational mobility and compaction of native state

Understanding the mechanism for sucrose-induced protein stabilization is important in many diverse fields, ranging from biochemistry and environmental physiology to pharmaceutical science. Timasheff and Lee [Lee, J. C. & Timasheff, S. N. (1981) J. Biol. Chem. 256, 7193-7201] have established that thermodynamic stabilization of proteins by sucrose is due to preferential exclusion of the sugar from the protein's surface, which increases protein chemical potential. The current study measures the preferential exclusion of 1 M sucrose from a protein drug, recombinant interleukin 1 receptor antagonist (rhIL-1ra). It is proposed that the degree of preferential exclusion and increase in chemical potential are directly proportional to the protein surface area and that, hence, the system will favor the protein state with the smallest surface area. This mechanism explains the observed sucrose-induced restriction of rhIL-1ra conformational fluctuations, which were studied by hydrogen-deuterium exchange and cysteine reactivity measurements. Furthermore, infrared spectroscopy of rhlL-1ra suggested that a more ordered native conformation is induced by sucrose. Electron paramagnetic resonance spectroscopy demonstrated that in the presence of sucrose, spin-labeled cysteine 116 becomes more buried in the protein's interior and that the hydrodynamic diameter of the protein is reduced. The preferential exclusion of sucrose from the protein and the resulting shift in the equilibrium between protein states toward the most compact conformation account for sucrose-induced effects on rhIL-1ra.     

Evaluation of the antireflux mechanism following laparoscopic fundoplication

BACKGROUND: Laparoscopic Nissen fundoplication is an effective procedure for the treatment of gastro-oesophageal reflux disease (GORD), but the underlying motility mechanisms that explain the success of this operation remain unclear. METHODS: Twenty patients with a history of GORD underwent stationary oesophageal manometry and prolonged ambulatory pH monitoring, both before and 3 months after fundoplication. RESULTS: Eighteen patients were completely cured of reflux symptoms and stopped all antireflux medication after operation. After fundoplication there was a significant increase (P < 0.01) in median resting lower oesophageal sphincter (LOS) pressure and length. Median residual LOS pressure during swallow-induced LOS relaxation also increased significantly after operation (P < 0.01). The number of reflux episodes decreased from a median of 48 to 3 after fundoplication (P < 0.01). The time at pH less than 4 decreased from 5.7 to 0 per cent in the supine position (P < 0.01), and from 9.8 to 0.2 per cent while upright (P < 0.001). CONCLUSION: Early subjective results at 3 months following laparoscopic antireflux surgery show improved symptoms. One of the mechanisms underlying the antireflux action of fundoplication is an increase in median residual LOS pressure at the gastro-oesophageal junction. This may be a purely mechanical effect of the fundic wrap extrinsic to the LOS.     

Experimental fetal tracheal ligation reverses the structural and physiological effects of pulmonary hypoplasia in congenital diaphragmatic hernia

Infants with congenital diaphragmatic hernia (DH) and profound pulmonary hypoplasia are currently unsalvageable. The authors previously demonstrated that tracheal ligation (TL) accelerates fetal lung growth and reverses the pulmonary hypoplasia of fetal nephrectomy. The purpose of this study was to determine if the pulmonary hypoplasia of experimental DH could be similarly reversed and, if so, whether the resulting lungs would show better function than those of their DH counterparts. Eighteen fetal lambs were divided into three experimental groups of six animals each. In group 1, DH was created at 90 days' gestation. In group 2, DH was created at 90 days' gestation and TL performed during the same operation. Group 3 consisted of sham-operated controls. These animals were delivered near full-term, and their lungs analyzed by standard morphometric techniques. Ten additional fetal lambs were divided into two experimental groups of five animals each. In group 4, DH was created at 90 days' gestation. In group 5, DH was created at 90 days' gestation and TL performed 20 days later, at 110 days' gestation. These animals were pressure-ventilated via tracheostomy over a 2-hour period in which PaO2, PaCO2, and compliance were measured. Intratracheal pressure (ITP) was measured at the time of delivery in all groups. Upon retrieval, DH animals had abdominal viscera in the chest and small lungs; in contrast, DH/TL animals had the herniated viscera reduced from the chest by enlarged lungs. DH/TL lungs showed markedly increased growth, with significant increases in lung volume:body weight ratio (LV:BW; P = .0001), alveolar surface area (ALV.SA; P = .0001), and alveolar number (ALV#) (P = .0001) when compared with those of the DH or control group. This growth was associated with a normal maturation pattern based on histological appearance, normal airspace fraction, and normal alveolar numerical density. ITP in the DH/TL group was increased when compared with that of DH and control animals (P = .0001). Total lung DNA and protein were both elevated in the DH/TL animals (P = .0001). However, the DNA:protein ratio remained normal, suggesting lung growth had occurred through cell proliferation, not by hypertrophy. When ventilated over a range of settings, DH/TL lungs were more compliant (P = .0001) and achieved higher PaO2s (P < .003) and lower PaCO2s (P = .0001) than their DH counterparts. From these data, the authors conclude: (1) Experimental fetal DH produces hypoplastic lungs that are not capable of adequate gas exchange with conventional ventilation.(ABSTRACT TRUNCATED AT 400 WORDS)     

Planar-flow spin-casting of molten metals: process behaviour

An experimental study of the planar-flow melt-spinning process was performed in order to gain a better understanding of the steady-state production of microcrystalline and amorphous ribbons. The dependence of the thickness of the ribbon product,T, on process parameters (wheel speed,U, nozzle/wheel gap,G, overpressure, ΔP, nozzle-slot breadth,R, and nozzle-slot width,W) was determined using an apparatus designed to deliver reproducible results. Thicknesses were reproducible to within 5%–8%. Guided by dimensional analysis, the non-dimensional thickness (T/G) was found to depend, within the experimental error, only on a non-dimensional pressure drop (ΔP/ρU ²) and slot breadth (R/G) for fixed thermal conditions. Data from the literature and our data, which considerably extend the range, correlate consistently on this basis. In contrast to the steady behaviour, the limits within which a uniform ribbon can be formed depend on a larger set of parameters; this dependence is sketched with the available data. Finally, a variety of observed ribbon surface textures (free meniscus side) is catalogued.     

A circuit approach to field computation

Many design objectives can be expressed more directly in terms of circuit parameters, such as capacitance and inductance, than in terms of the field vectors E and B. A simple, although radical, change is suggested to provide a closer link between the field and circuit views. The electric potential φ and magnetic vector A are defined, in energy terms, as the primary field quantities, and they are visualized as measures of the capacitance and inductance, respectively. E and B become auxiliary symbols denoting derivatives, so that the customary roles of the potentials and field vectors are reversed. Some of the practical advantages of the change are examined and are illustrated by example     

MODELISATION PRINCIPLES FOR DRYING OF GELS

When one wants to understand and model the drying of high water content gels, one needs to gather all thermal physical parameters and to derive a physical model based on independently measured parameters. We chose to work experimentally and theoretically on water diffusion and drying of spheres of polyacrylamide gel.

We have demonstrated the strong influence of vitreous transition on the relationship of water diffusivity with moisture content. Values of the diffusion coefficient and temperature shift factor for diffusion have been proposed.

Convective and micro-wave drying kinetics show the presence of a drying phase purely specific to radiation absorption. Finally, we have proposed a mathematical model containing independent physical parameters, which' not only predicts mass fluxes but also analyses critical physical phenomena.     

ART-EMAP: A neural network architecture for object recognition byevidence accumulation

A new neural network architecture is introduced for the recognition of pattern classes after supervised and unsupervised learning. Applications include spatio-temporal image understanding and prediction and 3D object recognition from a series of ambiguous 2D views. The architecture, called ART-EMAP, achieves a synthesis of adaptive resonance theory (ART) and spatial and temporal evidence integration for dynamic predictive mapping (EMAP). ART-EMAP extends the capabilities of fuzzy ARTMAP in four incremental stages. Stage 1 introduces distributed pattern representation at a view category field. Stage 2 adds a decision criterion to the mapping between view and object categories, delaying identification of ambiguous objects when faced with a low confidence prediction. Stage 3 augments the system with a field where evidence accumulates in medium-term memory. Stage 4 adds an unsupervised learning process to fine-tune performance after the limited initial period of supervised network training. Each ART-EMAP stage is illustrated with a benchmark simulation example, using both noisy and noise-free data.