LXR/ApoE Activation Restricts Innate Immune Suppression in Cancer

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Expression of Retinoid X Receptors in Human Dermal Fibroblasts

Retinoic acid (RA) is known to exert profound effects on growth and differentiation in human dermal fibroblasts. In the observations presented here, we examined the regulation of expression of members of the RXR multigene family in human dermal fibroblasts. We showed that the messenger RNAs for both RXRα and RXRβ are expressed in human fibroblasts, but that the messenger RNA for RXRγ is not detectable in these cells. Electrophoretic mobility shift studies of binding to the β2RARE in human dermal fibroblasts demonstrated that a single complex binds to β2RARE in the absence of RA. Stimulating cells with all-transRA induced a second complex. An antibody to the RXRβ protein supershifted both complexes, while an antibody to the RXRα S/B protein had no effect on the binding. These data demonstrate that RXRβ plays an important role in retinoid-regulated signal transduction pathways in human dermal fibroblasts and the regulation of expression of the RXR gene family is different from that of the RAR gene family.     

Teaching medical students how to break bad news

PROGRAM OBJECTIVE: To teach medical students to break bad news to patients and their families empathically and competently. SETTING: Seven teaching hospitals affiliated with the University of Toronto since 1987. PARTICIPANTS: All medical students in their third preclinical year. PROGRAM: The course presents a 6-point protocol to guide students in breaking bad news and comprises 2 half-day (3-hour) teaching sessions. Each session incorporates a video presentation, a discussion period and small-group teaching, consisting of exercises followed by 4 different role-playing scenarios conducted with the use of standardized patients. The course was evaluated through 2 questionnaires, 1 administered before and 1 after the course, which measured changes in the students'' attitude and strategy. Questionnaires were administered during 5 of the years since the course was started. A total of 914 precourse and 503 postcourse questionnaires were completed, of which 359 matched pairs of precourse and postcourse questionnaires were analysed to study any changes due to the course. OUTCOMES: Precourse questionnaires showed that 68% of the students had thought about the task of breaking bad news often or very often. Of the 56% of students who had seen clinicians performing this task, 75% felt that they had seen good examples. The proportion of the students who had a plan for how to conduct such an interview rose from 49% before the course to 92% after it, and the proportion who felt they might be reasonably competent in breaking bad news rose from 23% before the course to 74% after it. CONCLUSIONS: The subject of breaking bad news is important to medical students, and it is practicable to design a course to teach the basic techniques involved. Most students perceive such a course as enjoyable and useful and find that it increases their sense of competence and their ability to formulate a strategy for such situations.     

Alterations in Glial Fibrillary Acidic Protein (GFAP) mRNA Levels in the Hamster Facial Motor Nucleus: Effects of Axotomy and Testosterone

Testosterone propionate (TP) administered at the time of facial nerve injury in the hamster accelerates the rate of regeneration. In this study, we tested the hypothesis that the mechanism by which TP augments peripheral nerve regeneration involves regulation of glial fibrillary acidic protein (GFAP) mRNA in the facial motor nucleus. Castrated male hamsters were subjected to right facial nerve transection, with half the animals implanted subcutaneously with Silastic capsules containing exogenous TP and the remainder sham implanted. Postoperative survival times were 0.25, 1, 2, 4, 7, and 14 d. Qualitative/quantitative analyses of both film and emulsion autoradiograms were accomplished. Axotomy, with or without TP, resulted in a dramatic increase in GFAP mRNA levels by 1 d postoperative on the axotomized side, relative to controls. GFAP mRNA levels remained elevated throughout all postoperative times in both the nonhormone- and TP-treated animals. Qualitative examination of the film autoradiograms indicated a generalized decrease in the amount of GFAP mRNA in the control and axotomized nuclei of TP-treated animals when compared to the control and axotomized nuclei, respectively, of nonhormone-treated animals. Statistical comparison of the values obtained for both the film and emulsion autoradiograms confirmed this impression. Thus, while the injury-induced increases in GFAP mRNA expression were not blocked by TP, the overall extent of the increase was significantly tempered by steroid treatment. These data suggest that hormonal modulation of the astrocytic response to peripheral nerve injury may be a contributing factor in the ability of steroids to enhance the regenerative capacities of injured motor neurons.     

A new species of Taeniastrotos Cressey (Copepoda: Poecilostomatoida) from southern Brazil

A new species of Taeniastrotos is described from an ariid host, Cathrops spixii, caught in southern Brazil. It is the first member of the genus to be recorded from the Atlantic Ocean and can be distinguished from its four known congeners by the setation of the terminal endopodal segment of the fourth leg.     

Plant-growth regulators derived from the sweetener stevioside

A series of isosteviol derivatives such as aromatic esters and amino acid amides were synthesized. Their effects on seed germination and root elongation of the crop plants, Capsicum annuum, Lens culinaris medicus, Lycopersicon esculentum, Trifollium spp. and Triticum vulgare, were studied. The derivatives could be arranged into four groups: (1) seed germination inhibitors (2) root elongation inhibitors (3) root elongation inducers (4) general inhibitors.     

Staphylococcus aureusα-Toxin: Characterization of Protein/Lipid Interactions, 2D Crystallization on Lipid Monolayers, and 3D Structure

Staphylococcus aureusα-toxin was characterized with respect to surface activity and its interaction with lipid monolayers. The protein alone had a detergent-like behavior at the air/water interface. Its affinity was higher for negatively charged than for neutral phospholipids. The interaction was pH dependent, showing a maximum increase at pH 7.0. Only a small part of the protein oligomer appeared to be inserted into the monolayers. Crystalline sheets of α-toxin were formed using negatively charged phospholipids. Electron microscopy of such areas, at different tilt angles, allowed reconstruction of a three-dimensional model following image processing. The sheets analyzed consisted of two protein layers arranged on a tetragonal lattice. Under the conditions used to grow the crystals the toxin formed 90-Å-wide cylinders with a height of 70 Å. One of the imposed fourfold axes running perpendicular to the plane of the crystalline layer is positioned at a protein-deficient region which forms a 25-Å-wide pore through the oligomer.     

Venom of the crotaline snake Atropoides nummifer (jumping viper) from Guatemala and Honduras: comparative toxicological characterization,isolation of a myotoxic phospholipase A2 homologue and neutralization by two antivenoms

A comparative study was performed on the venoms of the crotaline snake Atropoides nummifer from Guatemala and Honduras. SDS-polyacrylamide gel electrophoresis, under reducing conditions, revealed a highly similar pattern of these venoms, and between them and the venom of the same species from Costa Rica. Similar patterns were also observed in ion-exchange chromatography on CM-Shephadex C-25, in which a highly basic myotoxic fraction was present. This fraction was devoid of phospholipase A₂ activity and strongly reacted, by enzyme-immunoassay, with an antiserum against Bothrops asper myotoxin II, a Lys-49 phospholipase A₂ homologue. A basic myotoxin of 16 kDa was isolated to homogeneity from the venom of A. nummifer from Honduras, showing amino acid composition and N-terminal sequence similar to those of Lys-49 phospholipase A₂ variants previously isolated from other crotaline snake venoms. Guatemalan and Honduran A. nummifer venoms have a qualitatively similar toxicological profile, characterized by: lethal; hemorrhagic; myotoxic; edema-forming; coagulant; and defibrinating activities, although there were significant quantitative variations in some of these activities between the two venoms. Neutralization of toxic activities by two commercially-available antivenoms in the region was studied. Polyvalent antivenom produced by Instituto Clodomiro Picado was effective in the neutralization of: lethal; hemorrhagic; myotoxic; coagulant; defibrinating; and phospholipase A₂ activities, but ineffective against edema-forming activity. On the other hand, MYN polyvalent antivenom neutralized: hemorrhagic; myotoxic; coagulant; defibrinating; and phospholipase A₂ activities, albeit with a lower potency than Instituto Clodomiro Picado antivenom. MYN antivenom failed to neutralize lethal and edema-forming activities of A. nummifer venoms.