Duodenoesophageal reflux induces esophageal adenocarcinoma without exogenous carcinogen

Central nervous system (CNS) disease is a major feature of simian immunodeficiency virus (SIV) infection of macaques. To define the spectrum of CNS lesions in SIV-infected macaques and the potential associations with viral strain and disease course, we performed a retrospective analysis of necropsies on 124 macaques with SIV-induced AIDS. Histologic evidence of CNS disease was observed in 71 (57.3%) of the 124 animals. SIV encephalitis was the most common CNS lesion occurring in 43.7% (31/71) of the animals with CNS disease and 25% of all animals. The incidence of SIVE correlated significantly with shortened survival (P=0.0207). In addition, SIVE was seen in 42.9% (15/35) of rapid progressors (animals that died within 200 days) compared to only 18% (16/89) of normal progressors (animals that lived longer than 200 days) (P=0.011). Animals with SIVE had higher viral loads in peripheral blood than those that did not, but this difference did not reach statistical significance. Similarly, while animals infected with uncloned SIVmac251 had a higher incidence of SIVE (27.5%; 14/51) than animals infected with molecularly cloned SIVmac239 and its T-cell tropic derivatives (18.5%; 10/54) this difference was not statistically significant. In this study rapid disease progression and SIVE were highly correlated making separation of viral determinants of virulence from those of neurovirulence difficult.     

The formation of cardiac-electric-field potentials on the surface of the heart and torso in vertebrate animals

The comparative electrophysiological study of excitation process in heart with different types of organization have laid the foundation for solution of the problems of formation of cardioelectric field. It was shown, that the form of extracellular potentials on the epicardium correlated with different types of ventricle myocardial activation. Animals with the "flash" type of myocardial depolarization in most cases have the negative extracellular potentials in the greater part of the epicardial ventricular surface. Animals with the consecutive type of myocardial activation--the positive and biphase potentials. All myocardial layers (epicardial, intramural and endocardial) are electrophysiologically informative.     

Deriving inherent optical properties from water color: a multiband quasi-analytical algorithm for optically deep waters

For open ocean and coastal waters, a multiband quasi-analytical algorithm is developed to retrieve absorption and backscattering coefficients, as well as absorption coefficients of phytoplankton pigments and gelbstoff. This algorithm is based on remote-sensing reflectance models derived from the radiative transfer equation, and values of total absorption and backscattering coefficients are analytically calculated from values of remote-sensing reflectance. In the calculation of total absorption coefficient, no spectral models for pigment and gelbstoff absorption coefficients are used. Actually those absorption coefficients are spectrally decomposed from the derived total absorption coefficient in a separate calculation. The algorithm is easy to understand and simple to implement. It can be applied to data from past and current satellite sensors, as well as to data from hyperspectral sensors. There are only limited empirical relationships involved in the algorithm, and they are for less important properties, which implies that the concept and details of the algorithm could be applied to many data for oceanic observations. The algorithm is applied to simulated data and field data, both non-case1, to test its performance, and the results are quite promising. More independent tests with field-measured data are desired to validate and improve this algorithm.     

Analysis of multilayered dielectric waveguides: variationaltreatment

A fast and near exact modal analysis is presented to obtain the propagation constants and electric field profiles for dielectric multilayered channel (rib) waveguides. Calculations are performed for a particular channel configuration and found to be in excellent agreement with those obtained using the finite difference method     

Validation of lucigenin as a chemiluminescent probe to monitor vascular superoxide as well as basal vascular nitric oxide production

Lucigenin has been widely used as a chemiluminescent substrate to monitor vascular superoxide (O*-2) formation. The validity of lucigenin for detection of O*-2 has been questioned because O*-2 is generated by lucigenin itself. It has been shown that the concentration of lucigenin is a critical parameter affecting the validity of this assay. In the present studies we evaluated a reduced concentration of lucigenin (5 microM) as a tool to quantify O*-2 production in vascular tissue. Lucigenin-induced effects on endothelial function were assessed by isometric tension recording of isolated aortic rings suspended in organ baths. The effects of lucigenin on O*-2 production were studied using spin trapping and electron spin resonance spectroscopy. Lucigenin at 250 microM but not at 5 microM caused a significant attenuation of endothelium-dependent relaxations to acetylcholine, which was prevented by pretreatment with superoxide dismutase. Spin-trapping studies revealed that lucigenin at 250 microM increased vascular O*-2 production several fold while 5 microM lucigenin did not stimulate O*-2 production. Inhibition of NO synthase by NG-momomethyl-l-arginine as well as the removal of the endothelium almost doubled lucigenin-derived chemiluminescence (LDCL), indicating that basal production of endothelium-derived NO depresses the baseline chemiluminescence signal. Thus, lucigenin at a concentration of 5 microM seems to be a sensitive and valid probe for assessing O*-2 in vascular tissue. It can also be used as an indirect probe to estimate basal vascular NO release.     

Vasopeptidase inhibitors: incorporation of geminal and spirocyclic substituted azepinones in mercaptoacyl dipeptides

A series of 7-(di)alkyl and spirocyclic substituted azepinones were generated and incorporated as conformationally restricted dipeptide surrogates in mercaptoacyl dipeptides. Clear structure-activity relationships with respect to both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP) activity in vitro were observed. The best in this series, compound 1g, a geminally dimethylated C-7-substituted azepinone, demonstrated excellent blood pressure lowering in animal models. Compound 1g (BMS-189921) is characterized by a good duration of activity and excellent oral efficacy in models relevant to ACE or NEP inhibition, and its activity is comparable to that of the clinically efficacious agent omapatrilat. Consequently this inhibitor has been advanced clinically for the treatment of hypertension and congestive heart failure.