Contribution of retinoic acid receptor beta isoforms to the formation of the conotruncal septum of the embryonic heart

To investigate the relative contribution of retinoic acid receptor (RAR)beta isoforms in conotruncal septation, RAR beta 1 and beta 3 were inactivated in the mouse. Mice lacking RAR beta 1 and beta 3 appear normal. Disruption of these isoforms in RAR alpha or RAR gamma null genetic backgrounds results in a high postpartum lethality. However, except for ocular defects found in RAR beta 1-3/RAR gamma compound mutants, the double null mutants display only abnormalities seen in single null mutants. This probably reflects a functional redundancy with other RARs, most notably with RAR beta 2 which is five- to sixfold more abundant than RAR beta 1 and beta 3 and whose domain of expression is largely overlapping. The conotruncal ridges form normally in retinoid X receptor (RXR)alpha/RAR beta compound mutants but fail to fuse, apparently as a result of excessive apoptosis of mesenchymal cells. Additionally, many cardiomyocytes in the conotruncal wall of these mutants appear necrotic. Although RAR beta 1 and beta 3 are expressed specifically in the conotruncal ridges, failure of fusion of these structures is not more frequent in RXR alpha/RAR beta 1-3 double null mutants than in RXR alpha single null mutants. Similarly, the disruption of the sole RAR beta 2 isoform in a RXR alpha null genetic background does not result in an increase of the frequency of conotruncal septum agenesis. However, this agenesis is fully penetrant in RXR alpha/RAR beta +/- mutants, which reflects distinct role of RXR alpha:RAR beta 1 (and beta 3) and RXR alpha:RAR beta 2 heterodimers in promoting the survival of conotruncal mesenchymal cells. Unexpectedly, we discovered that, in wild-type embryos, the conotruncal mesenchyme is a major site of morphogenetic cell death and that conotruncal myocytes are occasionally necrotic. Thus, excessive cell death in the conotruncus is a potential cause of ventricular septal defects in humans.     

Nuclear detection of cellular retinoic acid binding proteins I and II with new antibodies

Apart from the retinoic acid nuclear receptor family, there are two low molecular weight (15 kD) cellular retinoic acid binding proteins, named CRABPI and II. Mouse monoclonal and rabbit polyclonal antibodies were raised against these proteins by using as antigens either synthetic peptides corresponding to amino acid sequences unique to CRABPI or CRABPII, or purified CRABP proteins expressed in E. coli. Antibodies specific for mouse and/or human CRABPI and CRABPII were obtained and characterized by immunocytochemistry and immunoblotting. They allowed the detection not only of CRABPI but also of CRABPII in both nuclear and cytosolic extracts from transfected COS-1 cells, mouse embryos, and various cell lines.     

A program system interpreting recording of long-latency evoked potentials

An algorithm and a personal computer program for automatic distinguishing between EEC records containing evoked and no potentials, based on the detected invariants reflecting experts' experience in evoked potential analysis have been developed. The efficiency of the programme (its high accuracy and speed, low volume) has been demonstrated in the system for automatic determination of the hearing level by long-latent evoked potentials. It is easily modifiable to identify evoked potentials from other modalities (visual, somatosensory ones) in the systems using the traditional and/or up-to-date computerized EEC equipment.     

Properties controlling the diffusion and release of water-soluble solutes from poly(ethylene oxide) hydrogels: 3. Device geometry

The diffusive release from hydrogels can be determined by both composition and geometry. This paper presents a theoretical and experimental comparison of the release characteristics of proxyphylline in water-swollen slabs, spheres, and cylinders of a urethane cross-linked poly(ethylene oxide). Contrary to general conventional wisdom it was found that practically cylinders and spheres, which have considerable potential advantages for oral delivery, can provide good 'anomalous' rates for which the 'exponent of release' into water from the dry xerogels is c. 0.8 compared with 1.0 for zero order. An exponent of 0.94 was found for release into water from 'larger' xerogel flat slabs thus confirming that these configurations can provide essentially constant delivery formulations from which the active agent cannot be 'dumped'. For up to 40% total drug release, the theoretical release profiles were essentially of identical form for all three geometries in the swollen state and, as expected in theory and practice, showed an exponent for release of close to 0.5. However, the experimental release of proxyphylline was found to be more sustained from swollen spheres of these polymers than theory would predict. The half life times for release were further extended by approximately two and a half times for the initially dry devices compared with the initially swollen ones.     

Effect of Substructure on the Thermoelectric Power of aβ-Quenched ZrCrFe Alloy

β-quenching a Zr-1.15 wt％Cr-0.10 wt％Fe alloy produces a martensitic or a Widmanst(a|¨)tten transforma-tion morphology,or a mixture of the two,depending on the cooling rate.For the Widmanst(a|¨)tten structure,orthe mixed martensitic-Widmanst(a|¨)itten structure,a grain boundary phase is observed at most prior-β grainboundaries.X-ray line broadening analysis and the thermoelectric power(TEP)measurements of thesequenched samples show that not only the solubility of alloying elements in α-Zr matrix,but also substructure(microstrain,crystallite size and dislocation density)have an effect on TEP.Thus,TEP measurements are verywell suited for following the structural transformations taking place in Zr alloys during fabrication.