Mast Cell Chymase and Kidney Disease

A sizable part (~2%) of the human genome encodes for proteases. They are involved in many physiological processes, such as development, reproduction and inflammation, but also play a role in pathology. Mast cells (MC) contain a variety of MC specific proteases, the expression of which may differ between various MC subtypes. Amongst these proteases, chymase represents up to 25% of the total proteins in the MC and is released from cytoplasmic granules upon activation. Once secreted, it cleaves the targets in the local tissue environment, but may also act in lymph nodes infiltrated by MC, or systemically, when reaching the circulation during an inflammatory response. MC have been recognized as important components in the development of kidney disease. Based on this observation, MC chymase has gained interest following the discovery that it contributes to the angiotensin-converting enzyme’s independent generation of angiotensin II, an important inflammatory mediator in the development of kidney disease. Hence, progress regarding its role has been made based on studies using inhibitors but also on mice deficient in MC protease 4 (mMCP-4), the functional murine counterpart of human chymase. In this review, we discuss the role and actions of chymase in kidney disease. While initially believed to contribute to pathogenesis, the accumulated data favor a more subtle view, indicating that chymase may also have beneficial actions.     

ComWeb: An electronic classroom for teaching computer literacy

We have developed an electronic classroom environment based on an analog/digital hybrid network, ComWeb. This environment supplements traditional methods of presentation by providing powerful communication tools between the students and the teacher directed from the instructor's workstation. The instructor can access every student's workstation at any time to monitor the student's work or to transmit information from any source. ComWeb has facilities for individual and group supervision. It can be adapted for teaching deaf or hard of hearing students in a mainstream environment. We describe the implementation of a ComWeb-based classroom at our site. The performance of students in conventional sections of a computer literacy course is compared with that in a section using ComWeb. For most of the material, performance of students in the ComWeb based section was markedly superior.     

Predicting posttraumatic growth in breast cancer survivors.

Wide variability exists with respect to how breast cancer survivors respond to common psychological and psychosocial challenges of their disease, ranging from posttraumatic stress disorder to posttraumatic growth. This cross-sectional study examined contextual, disease-related, and intraindividual predictors of posttraumatic growth in 224 randomly selected breast cancer survivors. A series of hierarchical regression analyses found that age at diagnosis, marital status, employment, education, perceived intensity of disease, and active coping accounted for 34%, 35%, and 28% of the variance in growth in relationships with others, new possibilities, and appreciation for life. These findings suggest that a more comprehensive model of growth will be helpful in understanding the various factors that play a role in breast cancer survivors' perception of psychological and psychosocial growth. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Induction of early atherosclerosis in LDL-receptor-deficient mice immunized with beta2-glycoprotein I

BACKGROUND: Immunization with beta2-glycoprotein I (beta2GPI), the probable target of autoimmune anticardiolipin antibodies, results in experimental antiphospholipid syndrome in different mouse strains. The present study was undertaken to evaluate the effect of beta2GPI immunization on the progression of atherosclerosis. METHODS AND RESULTS: In the first experiment, 3 groups of LDL receptor-deficient (LDL-RD) mice (n=15 per group) were immunized with either beta2GPI or ovalbumin or were not immunized and were fed a chow diet for 12 weeks. In a second experiment, 3 groups of LDL-RD mice (n=10 per group) were immunized similarly and fed an atherogenic diet for 6 weeks. All beta2GPI-immunized mice developed high titers of anti-beta2GPI antibodies as well as a specific lymph node proliferation to beta2GPI. The average cholesterol levels did not differ between the mice fed similar diets, regardless of the immunization protocol. Atherosclerosis was enhanced in the beta2GPI-immunized mice (mean aortic lesion, 26 000+/-5700 microm2) in comparison with their ovalbumin-immunized (mean, 3000+/-1099 microm2; P<0.01) and nonimmunized (mean, 2250+/-700 microm2; P<0.01) littermates. The average lesion size in the beta2GPI-immunized mice fed an atherogenic diet (mean, 98 000+/-8305 microm2) was larger than the ovalbumin-immunized mice (mean, 81 250+/-12 933 microm2; P=NS) or the nonimmunized controls (mean, 75 625+/-7281 microm2; P=NS). The atherosclerotic plaques in the beta2GPI-immunized mice appeared to be more mature, and denser infiltration of CD4 lymphocytes was present in the subendothelium of the aortic sinuses from this group of mice. CONCLUSIONS: The results of the present study provide the first direct evidence for the proatherogenic effect of ss2GPI immunization and establish a new model for immune-mediated atherosclerosis.     

Novel polyurethane polyols for waterborne and high solids coatings

Recently developed oligomeric β-hydroxyalkyl urethane polyols are finding application as modifiers and crosslinkers for waterborne and high solids coatings. In waterborne coatings, urethane polyols can be used as modifiers for acrylic, polyester or alkyd melamine resin crosslinked coatings to replace the cosolvent. In high solids coatings, polyurethane polyols are being employed to raise the application solids, increase film hardness and water resistance, and exterior durability.

There are also applications for polyurethane diols as resin intermediates and in the preparation of blocked isocyanate crosslinkers. β-Hydroxyalkyl urethane diol or polyols can be prepared by an isocyanate reaction with a diol, such as 1,2-propylene glycol, but also by non-isocyanate processes. The non-isocyanate routes to urethanes can utilize carbon monoxide, carbon dioxide, urea or organic carbonates as a carbonyl source for the carbamic acid ester.

It is possible to split these urethanes to the isocyanate, but interest has concentrated on using the urethane intermediates directly in coating applications without going through the isocyanate. The structures reported are bis-hydroxyalkyl urethane intermediates and derivatives of these compounds.     

Chemical synthesis and physiological activity of sulfonium analogues of platelet activating factor

Phosphatidylsulfocholine (PSC), the sulfonium analogue of phosphatidylcholine (PC), occurs naturally in some diatoms. The replacement of the −N⁺(CH₃)₃ group by a −S⁺(CH₃)₂ results in an increase in the polar head group size in PSC relative to that of PC, consistent with the observed increase in permeability of PSC bilayers towards urea. It was of interest to see whether replacement of the −N⁺(CH₃)₃ group in platelet activating factor (PAF) by an −S⁺(CH₃)₂ group leads to any change in platelet aggregation or other physiological activity. Synthesis of the sulfonium analogue of PAF was carried out by suitable modifications of known procedures. The PAF-sulfonium analogue was found to have almost the same platelet aggregating activity as PAF itself, in the concentration range 1–20 μM, but a much lower activity in the range 0.01–1 μM. The analogue had little or no effect on the platelet aggregation activity of PAF when added in the concentration range 0.01–1 μM and had about half the hypotensive activity of PAF towards hypertensive CDF male rats. The sulfonium analogue, however, was much more cytotoxic to HL-60 cells than PAF itself, in the concentration range 0–15 μM; replacement of the acetate group by a benzyl group increased the cytotoxicity to the level of that of the methoxy analogue of PAF. Thus, replacement of the −N⁺(CH₃)₃ group by a −S⁺(CH₃)₂ group in the polar head group region of PAF results in a relatively small change in its platelet aggregation activity and a decrease in its hypotensive activity, but greatly increases its antitumor activity. Based on a paper presented at the Third International Conference on Platelet-Activating Factor and Structurally Related Alkyl Ether Lipids, Tokyo, Japan, May 8–12, 1989.     

Processing of High-Density Submicrometer Al2O3 for New Applications

Sintered corundum components with submicrometer grain sizes exhibit properties which enable numerous new applications. Wet powder processing is developed to associate minimum grain sizes at highest densities with the lowest population of macrodefects. A closest ratio of powder particle size and sintered grain size is important for obtaining most fine-grained microstructures. This target was approached best by using powders with particle sizes in the range of 100–200 nm rather than with smaller nanoparticles.     

Effect of Microstructure on the Tribological and Mechanical Properties of CuO-Doped 3Y-TZP Ceramics

Dense 8 mol% CuO-doped 3Y-TZP ceramics were prepared by pressureless sintering for 8 h at 1500° and 1550°C, respectively. Transmission electron spectroscopy revealed that the ceramic sintered at 1500°C exhibits grain boundaries free of any amorphous phase, while crystalline copper-oxide grains were found in the zirconia matrix, whereas the sample sintered at 1550°C contains a Cu-rich amorphous grain boundary layer. The tribological behavior of these materials was tested under dry-sliding conditions using a pin-on-disk tribometer. The material sintered at 1500°C showed self-lubrication resulting in a low coefficient of friction ( f ) of 0.2–0.3 and a low specific wear rate ( k ) ≪ 10⁻⁶ mm³·(N·m)⁻¹. In contrast, the material sintered at 1550°C showed poor tribological behavior ( f =0.8–0.9; k ≫ 10⁻⁶ mm³·(N·m)⁻¹ under the same conditions. The difference in the tribological behavior of these two materials was interpreted on the basis of mechanical properties and microstructural characteristics.     

Calcium can disrupt the SNARE protein complex on sea urchin egg secretory vesicles without irreversibly blocking fusion

The homotypic fusion of sea urchin egg cortical vesicles (CV) is a system in which to correlate the biochemistry and physiology of membrane fusion. Homologues of vesicle-associated membrane protein (VAMP), syntaxin, and SNAP-25 were identified in CV membranes. A VAMP and syntaxin immunoreactive band at a higher apparent molecular mass (approximately 70 kDa) was detected; extraction and analysis confirmed that the band contained VAMP, SNAP-25, and syntaxin. This complex was also identified by immunoprecipitation and by sucrose gradient analysis. VAMP in the complex was insensitive to proteolysis by tetanus toxin. All criteria identify the SNARE complex as that described in other secretory systems. Complexes exist pre-formed on individual CV membranes and form between contacting CV. Most notably, CV SNARE complexes are disrupted in response to [Ca2+]free that trigger maximal fusion. N-Ethylmaleimide, which blocks fusion at or before the Ca2+-triggering step, blocks complex disruption by Ca2+. However, disruption is not blocked by lysophosphatidylcholine, which transiently arrests a late stage of fusion. Since removal of lysophosphatidylcholine from Ca2+-treated CV is known to allow fusion, complex disruption occurs independently from the membrane fusion step. As Ca2+ disrupts rather than stabilizes the complex, the presumably coiled-coil SNARE interactions are not needed at the time of fusion. These findings rule out models of fusion in which SNARE complex formation goes to completion ("zippers-up") after Ca2+ binding removes a "fusion-clamp."