Retrovirus-mediated gene transfer of a human c-fos cDNA into mouse bone marrow stromal cells.

A cDNA encoding a complete human c-fos protein was isolated and inserted into two different murine MoMuLV-derived recombinant retroviruses allowing expression of c-fos protein in different cell types. One c-fos-expressing retrovirus, chosen for its ability to express high levels of proteins in fibroblast-like cells, was shown to potentiate long-term cultures of mouse bone marrow stromal cells in vitro and therefore constitutes a potential tool for immortalizing such cells. Moreover, when tested in an in vitro differentiation assay, stromal cells constitutively expressing c-fos favor the granulocyte differentiation of hematopoietic precursors. Interestingly, retroviruses expressing v-src and v-abl oncogenes, included as controls in our experiments, do not produce any detectable effects, whereas those expressing polyoma virus middle T antigen facilitate long-term growth in vitro of stromal cells that favor the macrophage differentiation pathway of bone marrow stem cells. Our observation supports the idea that constitutive expression of some oncogenes, including c-fos and polyoma virus middle T antigen, may influence cytokine production by bone marrow stromal cells.     

Césarienne, maladie mitrale et hypertension artérielle pulmonaire. Implications du monitorage hémodynamique sur la conduite de l'anesthésie

We present the case of a 25-year-old woman with mitral valve disease and severe pulmonary hypertension scheduled for Caesarean section under general anaesthesia. General anaesthesia for such cardiac patients requires usually high doses of fentanyl prior to intubation, which favours maternal inhalation and neonatal ventilatory depression. Invasive haemodynamic monitoring allowed a rapid sequence induction, with an optimal drug titration and an early recovery.     

Double anal canal: complication of rectal fecalith

Fecaliths and stercoraceous ulcerations are well-known complications of chronic constipation. The authors present the case of a double anal canal in an elderly man. This anorectal fistula (complex anal fistula) developed as a complication of an impacted rectal fecalith with resultant stercoraceous ulceration. Eventually, a persistent epithelialized canal developed and was demonstrated at double-contrast barium enema examination. The patient remained continent at all times.     

Neurochemistry and child and adolescent psychiatry.

This article reviews some of the neurochemistry and neurophysiology of three neurotransmitters: dopamine, norepinephrine, and serotonin. These neurotransmitters are selected because they appear to be involved in the regulation of several important behavioral systems that help regulate the interaction of the organism with its external environment, because many of the psychotropic drugs' modes of action may be result from their effects on these neurotransmitter systems, and because the majority of neurochemical studies in child psychiatry have focused on these three neurotransmitters. After the review of the neurotransmitter systems, neurochemical studies in several child psychiatric disorders are reviewed to illustrate possible biochemical/behavioral relationships in child psychiatry.     

Dlx5, a positive regulator of osteoblastogenesis, is essential for osteoblast-osteoclast coupling

The homeodomain protein Dlx5 is an activator of Runx2 (a key regulator of osteogenesis) and is thought to be an important regulator of bone formation. At present, however, the perinatal lethality of Dlx5-null mice has hampered the elucidation of its function in osteogenesis. Here we provide the first analysis of the effects of Dlx5 inactivation on bone development. Femurs of Dlx5-null mouse embryos at the end of gestation exhibit a reduction in both total and trabecular bone volume associated with increased trabecular separation and reduced trabecular number. These parameters are often associated with pathological conditions characterized by reduced osteoblast activity and increased bone resorption. Dlx5^−/− osteoblasts in culture display reduced proliferation and differentiation rate and reduction of Runx2, Osx, Osteocalcin and Bone Sialoprotein expression. In addition to impaired osteoblast function, Dlx5^−/− femurs exhibit significant increases in osteoclast number. As Dlx5 is not expressed by osteoclasts, we suggest that its osteoblastic expression might control osteoblast/osteoclast coupling. Cultured Dlx5^−/− osteoblasts displayed a higher RANKL/OPG ratio. Furthermore, Dlx5^−/− osteoblasts induced a higher number of TRAP-positive multinucleated cells in normal spleen cultures with a globally increased resorption activity. These findings suggest that Dlx5 is a central regulator of bone turnover as it activates bone formation directly and bone resorption indirectly.     

An observational study of noninvasive positive pressure ventilation in an out-of-hospital setting

Objective

Out-of-hospital clinical experience with noninvasive bilevel positive airway pressure (BiPAP) ventilation is extremely limited compared to inhospital management. The aims of this study were to assess the feasibility of out-of-hospital BiPAP ventilation in patients with acute respiratory distress of various origins, and to look for specific factors associated with failure of this respiratory support.

Methods

This 2-year prospective observational study assessed the failure rate of out-of-hospital BiPAP ventilation, the difficulties encountered, and factors predictive of failure by multivariate analysis.

Results

Overall, 138 patients were treated by out-of-hospital BiPAP for congestive heart failure (56%), chronic obstructive pulmonary disease exacerbation (28%), and acute respiratory failure (16%). Failure rate was 26% (35/138; 95% confidence interval, 18%-33%) (11 before and 24 after reaching hospital). Independent risk factors were the cause of respiratory distress (chronic obstructive pulmonary disease exacerbation; acute respiratory failure) and an audible air leakage.

Conclusions

The failure rate of BiPAP initiated out-of-hospital was no different from previous reports for inhospital failure rates. Failure was attributable to similar causes.     

A black-box re-weighting analysis can correct flawed simulation data

There is a great need for improved statistical sampling in a range of physical, chemical, and biological systems. Even simulations based on correct algorithms suffer from statistical error, which can be substantial or even dominant when slow processes are involved. Further, in key biomolecular applications, such as the determination of protein structures from NMR data, non-Boltzmann-distributed ensembles are generated. We therefore have developed the "black-box" strategy for re-weighting a set of configurations generated by arbitrary means to produce an ensemble distributed according to any target distribution. In contrast to previous algorithmic efforts, the black-box approach exploits the configuration-space density observed in a simulation, rather than assuming a desired distribution has been generated. Successful implementations of the strategy, which reduce both statistical error and bias, are developed for a one-dimensional system, and a 50-atom peptide, for which the correct 250-to-1 population ratio is recovered from a heavily biased ensemble.     

Rapid electrophysiological brain responses are influenced by both valence and magnitude of monetary rewards

Abstract Negative outcomes, as identified from external feedback, cause a short-latency negative deflection in the event-related potential (ERP) waveform over medial frontal electrode sites. This brain response, which has been called an "error related negativity" (ERN) or "medial frontal negativity" (MFN), may reflect a coarse evaluation of performance outcomes, such as the valence of a reward within a monetary gambling task. Yet, for feedback to lead to the adaptive control of behavior, other information concerning reward outcomes besides experienced valence may also be important. Here, we used a gambling task in which subjects chose between two options that could vary in both outcome valence (gain or loss) and outcome magnitude (larger or smaller). We measured changes in brain ERP responses associated with the presentation of the outcomes. We found, as shown in prior studies, that valence of the chosen outcome has an early effect upon frontal ERPs, with maximal difference observed at approximately 250 msec. However, our results demonstrated that the early ERP responses to outcome feedback were driven not just by valence but by the combination of valence and magnitude for both chosen and unchosen options. Beginning even earlier, at around 150 msec, responses to high-consequence outcomes resulted in a greater, more centrally distributed, positive potential than those involving low-consequence outcomes, independent of valence. Furthermore, the amplitude of these early effects was significantly modulated by the sequence of outcomes in previous trials. These results indicate that early evaluation of feedback goes beyond simple identification of valence-it involves the consideration of multiple factors, including outcome magnitude, context of unchosen options, and prior history.