Critical role for the tyrosine kinase Syk in signalling through the high affinity IgE receptor of mast cells

Activation of the high affinity IgE receptor (Fc epsilon RI) of mast cells, a member of the antigen receptor family, leads to the release of allergic mediators, a critical event in the onset of immediate hypersensitivity. Stimulation of Fc epsilon RI results in the rapid association and activation of the Syk tyrosine kinase. Using Syk-deficient mast cells we show that they fail to degranulate, synthesize leukotrienes and secrete cytokines when stimulated through Fc epsilon RI, conclusively demonstrating an essential role for Syk in Fc epsilon RI signalling. Furthermore, our data strongly supports a model of Fc epsilon RI engagement leading to the sequential activation of the tyrosine kinases Lyn and then Syk. A similar mechanism is likely to apply to signal transduction through all members of the antigen receptor family.     

Malignant atrophic papulosis (Degos'' disease) with extensive cardiopulmonary involvement

Unilateral Moyamoya disease presents as unilateral stenosis or obstruction of the supraclinoid internal carotid artery, which causes cerebral hypoperfusion resulting in seizures or TIA-like attacks. In severe cases, surgical treatment is performed with superficial temporal artery-middle cerebral artery anastomosis. In mild cases, conservative management is the treatment of choice. Flunarizine is a calcium ion anti-blocking agent, whose primary effect is that the cerebral vessels have been used for the treatment of postcerebrovascular disorders. Recently, it has been suggested that flunarizine could be used to treat Moyamoya disease. This report documents the efficacy of flunarizine to improve regional cerebral perfusion in Moyamoya disease.     

Serial changes of natural antithrombotics during myocardial ischemia-reperfusion in swine. Effects of magnesium, diltiazem, and a novel Mac-1 inhibitor

Plasma antithrombin-III (AT-III), protein S, and protein C were measured during myocardial stunning (MS) and acute myocardial infarction (AMI). The effects of magnesium (Mg), diltiazem, and a Mac-1 inhibitor on their plasma levels were elucidated. Forty-nine open-chest swine underwent brief (8 min) or prolonged (50 min) coronary artery occlusion followed by reperfusion. During MS an increase in the plasma AT-III (from 98.5 +/- 3.38% to 138.1 +/- 3.6%) during the early occlusion phase, without any further changes was observed. The profile of total protein S was not changed during MS. Protein C increased at the end of occlusion (from 45.3 +/- 1.8% to 55.7 +/- 1.4%) reaching a peak (64.5 +/- 1.4%) at the beginning of reperfusion. When compared with controls, no significant differences were found in the antithrombotics profile during MS after pretreatment with Mac-1 inhibitor. For the AMI, the AT-III decreased during occlusion (from 98.5 +/- 3.4% to 61.0 +/- 3.6%). The protein S decreased during occlusion with the lowest level at 1 h of reperfusion (from 71.8 +/- 2.2% to 46.7 +/- 1.0%), followed by an increase during late reperfusion (59.2 +/- 1.5%). Contrarily, protein C increased during occlusion and early reperfusion (from 44.7 +/- 2.6% to 79.4 +/- 2.4%), but declined to 49.6 +/- 2.5% thereafter. In both Mg and diltiazem-treated swine, protein C was higher at the end of occlusion and during the entire reperfusion period compared with controls. Mg and diltiazem therapy was associated with the slight elevation of plasma AT-III. The patterns for protein S level during ischemia-reperfusion were similar with the controls. Protein S was higher at the end of occlusion and through the entire reperfusion in the NPC 15669-treated animals when compared with the controls. Mac-1 inhibition was associated with the elevated protein C during late reperfusion. Ability of Mg, diltiazem, and Mac-1 inhibitor to favorably modulate the plasma level of antithrombotics have direct clinical implications for the use of these agents in patients with acute coronary artery syndromes.     

Innate metabolic differences and mutagen sensitivity of Drosophila melanogaster. I. Radiosensitivity of hyperkinetic mutant

The sensitivity to gamma-rays of a hyperkinetic mutant (HK1), characterized by high metabolic activity, has been studied and compared with gamma-ray sensitivity of the wild-type Oregon-K. Radiation damage, as measured by the frequency of induced dominant lethals (DL) and sex-linked recessive lethals (SLRL), was more in HK1 as compared with Or-K. The maximal sensitivity differences for these parameters were observed in the first brood. Translocations, on the contrary, were in general fewer in the HK1 compared with Or-K. These results have been interpreted in terms of reduced repair of mutational lesions in the energy-stressed cells of KH1.     

Factor analysis model evaluation through likelihood cross-validation

Medical research studies utilize survey instruments consisting of responses to multiple items combined into one or more scales. These studies can benefit from methods for evaluating those scales. Such an approach is presented for evaluating exploratory and confirmatory factor analysis models with decisions about covariance structure, including the number of factors, the factor extraction procedure, the allocation of survey items to summated scales and the extent of inter-scale dependence, made objectively using a likelihood-based form of cross-validation. This approach is demonstrated through example analyses using baseline data for three survey instruments from a clinical trial involving adolescents with type 1 diabetes.     

A novel system for self-validating adhesive joints

A self-validating adhesive system is proposed in which ‘zero volume unbonds’ or ‘kissing’ bonds, which are undetectable by NDE techniques, may be filled and bonded by a secondary component in the adhesive during cure. The system shows the principal criteria required for such a smart system, and has been shown to enhance the strength of a bonded joint without undue deterioration in durability or water uptake.