Calcium-activated neutral protease activity is decreased in PC12 cells after ethanol exposure

Calcium-activated neutral protease activity was determined in PC12 cells exposed to ethanol for 96 h using a fluorescence-based assay with N-succinyl-Leu-Tyr 7-amido-4-methylcoumarin as the substrate. Stimulated activity was measured at high (1,400 microM) or low (140 microM) Ca2+ concentrations in the presence of 20 microM ionomycin. Kinetic parameters were derived by fitting a model relating fluorescence intensity to time: F(t) = F(final)*(1 - e(-k(obs)t). Cell extracts were subjected to nondenaturing gel electrophoresis and casein zymography with quantification of the activity of the two calpain isoforms. Exposure to ethanol significantly decreased whole cell calpain activity measured by k(obs) beginning at 20 mM, to 27.8% of control at 1,400 microM Ca2+ and 29.2% of control at 140 microM Ca2+ in the presence of 20 microM ionomycin. No changes in mu-calpain or m-calpain activities were found in cell extracts from cells exposed to 20 mM ethanol, whereas at 40 and 80 mM ethanol, significant decreases in both mu-calpain and m-calpain activities were discovered.     

Aorto-left atrial fistula in prosthetic aortic endocarditis

Aortic valve endocarditis commonly leads to the formation of a root abscess, but fistulae are uncommon. The echocardiographic findings in a patient with Streptococcus viridans endocarditis of a prosthetic aortic valve associated with a fistula between the aorta and the left atrium are presented. The diagnosis was made by transthoracic echocardiography, although the transesophageal study gave higher resolution views and allowed a more confident exclusion of mitral valve involvement.     

4 beta, 15-Diacetoxyscirpenol induces cytotoxicity and alterations in phagocytic and Fc-receptor expression functions in chicken macrophages in vitro

Teleoperation is frequently performed with misalignments between operator or camera viewing direction and controller orientation. Examples of this occur in endoscopic surgery and in teleoperation with multiple camera views. The objective of this study was to find a method to automatically compensate for those misalignments so that human operators performing tasks under such scenarios could achieve levels of performance comparable to aligned conditions without additional training requirements. In this paper we report on a set of experiments conducted to test a method developed for that purpose. Participants were asked to track a randomly moving target on a computer display using a cursor controlled with a joystick. Performance was recorded under various visual-motor misalignments with and without automated compensation. Results indicated significant improvements in operator performance through use of automatic compensation only under certain types of misalignment. Actual or potential applications of this research include teleoperation and endoscopic surgery.     

Broad-band pulse performance of short helices

Helical antennas are popular and well characterized for CW frequency domain performance. Renewed interest in time-domain applications of electromagnetics, such as impulse radar, makes accurate time-domain data on broad-band antennas desirable. Although the principal endfire helix radiation mode has been extensively studied in the frequency domain, other modes important in pulse operation are poorly characterized, making a total Fourier transform approach difficult. We have performed impulse tests on helices with two to five turns, establishing novel features of the response and confirming some aspects of frequency domain data. Quick comparisons to time and frequency-domain modeling codes indicate good correspondence of gross features. Successful octave band-pulse operation was achieved, and a few features of helix pulse response invite further investigation     

Peak expiratory flow rate control chart in asthma care: chart construction and use in asthma care

We have analyzed X-chromosome inactivation patterns in lymphocytes of 264 females from 38 families not known to have any genetic disease. Quantitative measures of X-inactivation showed strong sister-sister correlation in the degree of departure from equal numbers of cells having each X chromosome active, suggesting heritability of this phenotype. Strong sister-sister correlation was also observed for the fraction of cells having the same parent's X chromosome active, consistent with the possibility that this trait might be controlled by a cis-acting, X-linked gene. We used a sib-pair approach to determine whether X-inactivation phenotype was linked to loci in any region of the X chromosome. Both quantitative and discrete measures of X-inactivation phenotype showed evidence of linkage to markers in the region of the X inactivation center (XIC). The quantitative measure of X-inactivation phenotype used in our study also showed linkage to loci at Xq25-q26. This study provides the first evidence for X-linked inheritance of X chromosome inactivation phenotype derived from linkage analysis in phenotypically normal human families.     

Characterization of Apo-Form Selective Inhibition of Indoleamine 2,3-Dioxygenase**

Indoleamine-2,3-dioxygenase 1 (IDO1) is a heme-containing enzyme that catalyzes the rate-limiting step in the kynurenine pathway of tryptophan (TRP) metabolism. As it is an inflammation-induced immunoregulatory enzyme, pharmacological inhibition of IDO1 activity is currently being pursued as a potential therapeutic tool for the treatment of cancer and other disease states. As such, a detailed understanding of the mechanism of action of IDO1 inhibitors with various mechanisms of inhibition is of great interest. Comparison of an apo-form-binding IDO1 inhibitor (GSK5628) to the heme-coordinating compound, epacadostat (Incyte), allows us to explore the details of the apo-binding inhibition of IDO1. Herein, we demonstrate that GSK5628 inhibits IDO1 by competing with heme for binding to a heme-free conformation of the enzyme (apo-IDO1), whereas epacadostat coordinates its binding with the iron atom of the IDO1 heme cofactor. Comparison of these two compounds in cellular systems reveals a long-lasting inhibitory effect of GSK5628, previously undescribed for other known IDO1 inhibitors. Detailed characterization of this apo-binding mechanism for IDO1 inhibition might help design superior inhibitors or could confer a unique competitive advantage over other IDO1 inhibitors vis-à-vis specificity and pharmacokinetic parameters.