Tryptase mediates hyperresponsiveness in isolated guinea pig bronchi

Hyperresponsiveness of airway smooth muscle to allergens and environmental factors has long been associated with the pathophysiology of asthma. Tryptase, a serine protease of lung mast cells, has been implicated as one of the mediators involved in the induction of hyperresponsiveness. As a consequence, tryptase inhibitors have become the subject of study as potential novel therapeutic agents for asthma. Secretory leukocyte protease inhibitor (SLPI) is a naturally occurring protein of human airways which exhibits anti-tryptase activity. To assess the potential therapeutic utility of SLPI in asthma, its effects were evaluated using in vitro and ex vivo models of airway hyperresponsiveness and compared with the effects of the small molecule tryptase inhibitor APC-366. Our results demonstrate that SLPI inhibits tryptase-mediated hyperresponsiveness in vitro and attenuates the hyperresponsiveness observed in airway smooth muscle from antigen-sensitized animals subjected to antigen exposure. The small molecule tryptase inhibitor APC-366 has a similar inhibitory effect. Thus, tryptase appears to be a significant contributor to the development of hyperresponsiveness in these models. To the extent that tryptase contributes to the development and progression of asthma, SLPI may possess therapeutic potential in this disease setting.     

Short-wave cone signal in the red-green detection mechanism

Previous work shows that the red-green (RG) detection mechanism is highly sensitive, responding to equal and opposite long-wave (L) and middle-wave (M) cone contrast signals. This mechanism mediates red-green hue judgements under many conditions. We show that the RG detection mechanism also receives a weak input from the short-wave (S) cones that supports the L signal and equally opposes M. This was demonstrated with a pedestal paradigm, in which weak S cone flicker facilitates discrimination and detection of red-green flicker. Also, a near-threshold +S cone flash facilitates detection of red flashes and inhibits green flashes, and a near-threshold -S cone flash facilitates detection of green flashes and inhibits red flashes. The S contrast weight in RG is small relative to the L and M contrast weights. However, a comparison of our results with other studies suggests that the strength of the absolute S cone contrast contribution to the RG detection mechanism is 1/4 to 1/3 the strength of the S contribution to the blue-yellow (BY) detection mechanism. Thus, the S weight in RG is a significant fraction of the S weight in BY. This has important implications for the 'cardinal' color mechanisms, for it predicts that for detection or discrimination, the mechanisms limiting performance do not lie on orthogonal M-L and S axes within the equiluminant color plane.     

Hepatic hemangioma. Analysis of 103 cases. Clinical considerations and imaging methods

Hemangiomas are the most common benign vascular tumor found in the liver. In this study, 103 cases of hepatic hemangiomas were analysed in a retrospective manner. Image aspects such as those seen in ultrassonography, computed tomography, nuclear magnetic resonance and arteriography are discussed. The incidence was higher amongst the female sex, between individuals from 40 to 60 years old, which presented predominantly without symptoms (66%) and localized mainly in the right hepatic lobe (74%). The meaning of those aspects, when adopted, permits the clinicians to differentiate benign from malignant nodular lesions in the liver.     

Multi-component T1 relaxation and magnetisation transfer in peripheral nerve

Corneas of diabetic patients have abnormal healing and epithelial adhesion, which may be due to alterations of the corneal extracellular matrix (ECM) and basement membrane (BM). To identify such alterations, various ECM and BM components and integrin receptors were studied by immunofluorescence on sections of normal and diabetic human corneas. Age-matched corneas from 15 normal subjects, 10 diabetics without diabetic retinopathy (DR), and 12 diabetics with DR were used. In DR corneas, the composition of the central epithelial BM was markedly altered, compared to normal or non-DR diabetic corneas. In most cases the staining for entactin/nidogen and for chains of laminin-1 (alpha1beta1gamma1) and laminin-10 (alpha5beta1gamma1 was very weak, discontinuous, or absent over large areas. Other BM components displayed less frequent changes. The staining for alpha3beta1 (VLA-3) laminin binding integrin was also weak and discontinuous in DR corneal epithelium. Components of stromal ECM remained unchanged even in DR corneas. Therefore, distinct changes were identified in the composition of the epithelial BM in DR corneas. They may be due to increased degradation or decreased synthesis of BM components and related integrins. These alterations may directly contribute to the epithelial adhesion and wound healing abnormalities found in diabetic corneas.     

An essential role for retinoid receptors RARbeta and RXRgamma in long-term potentiation and depression

Hippocampal long-term potentiation (LTP) and long-term depression (LTD) are the most widely studied forms of synaptic plasticity thought to underlie spatial learning and memory. We report here that RARbeta deficiency in mice virtually eliminates hippocampal CA1 LTP and LTD. It also results in substantial performance deficits in spatial learning and memory tasks. Surprisingly, RXRgamma null mice exhibit a distinct phenotype in which LTD is lost whereas LTP is normal. Thus, while retinoid receptors contribute to both LTP and LTD, they do so in different ways. These findings not only genetically uncouple LTP and LTD but also reveal a novel and unexpected role for vitamin A in higher cognitive functions.     

Sulfasalazine in the treatment of juvenile chronic arthritis: a randomized, double-blind, placebo-controlled, multicenter study. Dutch Juvenile Chronic Arthritis Study Group

AIMS: To determine whether left ventricular volumes and ejection fractions calculated from single plane two-dimensional echocardiograms using the algorithm (0.85A2L) correlate with those calculated using the biplane Simpson's method, and whether small changes in volumes and ejection fraction occurring post-infarction could be detected from single-plane as well as from biplane two-dimensional echocardiograms. METHODS AND RESULTS: Serial two-dimensional echocardiograms were obtained in 371 patients from the DEFIANT II trial a mean of 2 days, 1 week and 6 months post-infarction. Single plane volumes from the apical four chamber and apical long axis correlated closely with biplane Simpson's left ventricular volumes. Both single-plane left ventricular volumes significantly over-estimated biplane Simpson's volumes. Biplane Simpson's ejection fractions were consistently slightly under-estimated from the single-plane images. Differences between biplane Simpson's and single-plane volumes increased independently with increasing left ventricular size and distortion. The small changes in left ventricular volumes and ejection fraction over time were as reliably detected from single plane as from biplane images. CONCLUSION: Single-plane left ventricular volumes over-estimate biplane Simpson's volumes and under-estimate ejection fraction, and these discrepancies are amplified in dilated hearts with abnormal shape.     

Antonovsky's sense of coherence: theoretical basis of psychoeducation in schizophrenia

Psychoeducational models have been found to be effective interventions for people with schizophrenia. However, a unifying theoretical basis for these models has not been articulated. This article explicates the sense of coherence theory developed by A. Antonovsky (1987) and demonstrates its utility as a framework for conceptualizing the basis for the effectiveness of psychoeducational programs.     

Pulpal response to a resin-modified glass-ionomer material on nonexposed and exposed monkey pulps

OBJECTIVE: This study evaluated the biocompatibility of a resin-modified glass-ionomer material on monkey pulps. METHOD AND MATERIALS: Standardized Class V cavities were prepared in 112 teeth distributed in six healthy adult monkeys. The resin-modified glass-ionomer cement was placed in 24 nonexposed and 36 exposed pulps according to manufacturer's instructions. ZOE was used as a control in nonexposed pulps, while calcium hydroxide was used as a control for exposed pulps. Tissues were collected at 6 to 7, 21 to 27, and 90 to 97 days. After demineralization, the teeth were serially sectioned, stained, and observed by light microscopy. RESULTS: Except for one resin-modified glass-ionomer pulp at 6 days, there were no differences between the responses of nonexposed pulps to resin-modified glass-ionomer specimens and ZOE controls. In exposed pulps, eight of 36 resin-modified glass-ionomer pulps showed various grades of inflammatory response, all associated with stained bacteria. Pulpal healing was similar in both resin-modified glass-ionomer and calcium hydroxide direct-capped exposures. Twenty-two of 26 exposed pulps restored with the resin-modified glass-ionomer cement showed dentin bridge formation at 21 and 97 days. CONCLUSION: The resin-modified glass-ionomer material exhibited acceptable biologic compatibility in exposed and nonexposed cavities.