Massive pulmonary embolism presenting as disseminated intravascular coagulation.

Disseminated intravascular coagulation (DIC) can be defined as evidence of activation of the coagulation mechanism resulting in proteolysis of fibrinogen by thrombin and plasmin and an acute thrombocytopenia. The association of pulmonary embolism (PE) with DIC has recently been reported but in reviewing recent textbooks of hematology, there is no mention of PE as a cause of DIC. Clinicians need to be made aware of this association since it affects the patient who is thought to be autoanticoagulated as well as the patient who has DIC of unknown cause. PE needs to be included in the differential diagnosis of an autoanticoagulated state and in DIC of unknown etiology. In both instances the recommended treatment is full-dose intravenous heparin therapy

Activation of Protein Kinase A and Exchange Protein Directly Activated by cAMP Promotes Adipocyte Differentiation of Human Mesenchymal Stem Cells

Human mesenchymal stem cells are primary multipotent cells capable of differentiating into several cell types including adipocytes when cultured under defined in vitro conditions. In the present study we investigated the role of cAMP signaling and its downstream effectors, protein kinase A (PKA) and exchange protein directly activated by cAMP (Epac) in adipocyte conversion of human mesenchymal stem cells derived from adipose tissue (hMADS). We show that cAMP signaling involving the simultaneous activation of both PKA- and Epac-dependent signaling is critical for this process even in the presence of the strong adipogenic inducers insulin, dexamethasone, and rosiglitazone, thereby clearly distinguishing the hMADS cells from murine preadipocytes cell lines, where rosiglitazone together with dexamethasone and insulin strongly promotes adipocyte differentiation. We further show that prostaglandin I2 (PGI2) may fully substitute for the cAMP-elevating agent isobutylmethylxanthine (IBMX). Moreover, selective activation of Epac-dependent signaling promoted adipocyte differentiation when the Rho-associated kinase (ROCK) was inhibited. Unlike the case for murine preadipocytes cell lines, long-chain fatty acids, like arachidonic acid, did not promote adipocyte differentiation of hMADS cells in the absence of a PPARγ agonist. However, prolonged treatment with the synthetic PPARδ agonist L165041 promoted adipocyte differentiation of hMADS cells in the presence of IBMX. Taken together our results emphasize the need for cAMP signaling in concert with treatment with a PPARγ or PPARδ agonist to secure efficient adipocyte differentiation of human hMADS mesenchymal stem cells

Transcriptional regulatory program in wild-type and retinoblastoma gene-deficient mouse embryonic fibroblasts during adipocyte differentiation

<p>Abstract</p> <p>Background</p> <p>Although many molecular regulators of adipogenesis have been identified a comprehensive catalogue of components is still missing. Recent studies showed that the retinoblastoma protein (pRb) was expressed in the cell cycle and late cellular differentiation phase during adipogenesis. To investigate this dual role of pRb in the early and late stages of adipogenesis we used microarrays to perform a comprehensive systems-level analysis of the common transcriptional program of the classic 3T3-L1 preadipocyte cell line, wild-type mouse embryonic fibroblasts (MEFs), and retinoblastoma gene-deficient MEFs (Rb-/- MEFs).</p> <p>Findings</p> <p>Comparative analysis of the expression profiles of 3T3-L1 cells and wild-type MEFs revealed genes involved specifically in early regulation of the adipocyte differentiation as well as secreted factors and signaling molecules regulating the later phase of differentiation. In an attempt to identify transcription factors regulating adipogenesis, bioinformatics analysis of the promoters of coordinately and highly expressed genes was performed. We were able to identify a number of high-confidence target genes for follow-up experimental studies. Additionally, combination of experimental data and computational analyses pinpointed a feedback-loop between Pparg and Foxo1.</p> <p>To analyze the effects of the retinoblastoma protein at the transcriptional level we chose a perturbated system (Rb-/- MEFs) for comparison to the transcriptional program of wild-type MEFs. Gene ontology analysis of 64 deregulated genes showed that the Rb-/- MEF model exhibits a brown(-like) adipocyte phenotype. Additionally, the analysis results indicate a different or additional role for pRb family member involvement in the lineage commitment.</p> <p>Conclusion</p> <p>In this study a number of commonly modulated genes during adipogenesis in 3T3-L1 cells and MEFs, potential transcriptional regulation mechanisms, and differentially regulated targets during adipocyte differentiation of Rb-/- MEFs could be identified. These data and the analysis provide a starting point for further experimental studies to identify target genes for pharmacological intervention and ultimately remodeling of white adipose tissue into brown adipose tissue.</p

UCP1 Induction during Recruitment of Brown Adipocytes in White Adipose Tissue Is Dependent on Cyclooxygenase Activity

Background The uncoupling protein 1 (UCP1) is a hallmark of brown adipocytes and pivotal for cold- and diet-induced thermogenesis. Methodology/Principal Findings Here we report that cyclooxygenase (COX) activity and prostaglandin E2 (PGE2) are crucially involved in induction of UCP1 expression in inguinal white adipocytes, but not in classic interscapular brown adipocytes. Cold-induced expression of UCP1 in inguinal white adipocytes was repressed in COX2 knockout (KO) mice and by administration of the COX inhibitor indomethacin in wild-type mice. Indomethacin repressed β-adrenergic induction of UCP1 expression in primary inguinal adipocytes. The use of PGE2 receptor antagonists implicated EP4 as a main PGE2 receptor, and injection of the stable PGE2 analog (EP3/4 agonist) 16,16 dm PGE2 induced UCP1 expression in inguinal white adipose tissue. Inhibition of COX activity attenuated diet-induced UCP1 expression and increased energy efficiency and adipose tissue mass in obesity-resistant mice kept at thermoneutrality. Conclusions/Significance Our findings provide evidence that induction of UCP1 expression in white adipose tissue, but not in classic interscapular brown adipose tissue is dependent on cyclooxygenase activity. Our results indicate that cyclooxygenase-dependent induction of UCP1 expression in white adipose tissues is important for diet-induced thermogenesis providing support for a surprising role of COX activity in the control of energy balance and obesity development

Geometry of extensional faults developed at slow-spreading centres from seismic reflection data in the Central Atlantic (Canary Basin)

We present depth images, from portions of profiles that are close to flow-lines, of Cretaceous oceanic crust in the eastern Central Atlantic. Compared with post-stack time migrations, the images illustrate the improvement resulting from the application of pre-stack depth migration. The images document the scale and geometry of normal faulting in oceanic crust formed over 25 Myr at a half-spreading rate of less than 10 mm yr−1, and the variation in extensional style with position within the spreading segment. Away from major fault zones (FZs), most faults are subplanar, dip more than 35°, are associated with moderate basement relief (0.2–1 km relief) and may penetrate to deep crustal levels. These faults could be related to the lifting of the lithosphere out of the median valley to the flanking mountains. Also observed away from FZs are gently dipping to subhorizontal reflections in the upper crust, which resemble detachment faults. In contrast, the inside corner crust is more rugged, with basement highs rising up to 2 km above the intervening basins. This larger-scale topography is associated with a different style of faulting: the depth images reveal gently dipping (<35°) faults that are rooted in the deep crust and that project to the ridgeward flank of the dome-shaped large basement highs (1–2 km vertical relief). The faults seem to continue as the ridge-facing flank of these highs and some may extend over the crest of the high to breakaways beyond. In this case, the domal highs that form the exhumed footwall to the faults can be described as oceanic core complexes. These controlling faults are up to 20 km long and have a heave of ∼10 km, sufficient to have accommodated up to 50 per cent extension and to have exhumed deep crustal and perhaps even mantle rocks. We suggest that similar faults can explain the structure and lithologies found at megamullion structures (oceanic core complexes) at inside corners near the present-day spreading ridge

Medical consequences of acute exposure to high altitude.

People who ascend rapidly to altitudes greater than 3,000 meters (10,000 ft) may become ill; rarely, some may die from an inability to adapt to hypoxia. Age, pre-existing cardiopulmonary or hematologic disease, and the rate and degree of ascent are known to limit man's adaptation to high altitudes. Other factors, such as blunted hypoxic respiratory drive and sublinical disease of the pulmonary vascular bed are probably also important. Pre-exposure with acetozolamide (Diamox) helps, but once symptoms of high altitude pulmonary edema (HAPE) occur, supplemental oxygen and rapid descent to lower altitudes are the only known remedies. In view of the steady increase in the number of people who work and play at high altitudes, physicians must understand the pathophysiologic mechanisms involved in order to treat properly and to counsel patients

Toxic substances in the environment affecting respiratory function of people in Hawaii.

In this trilogy we have collected data from authors who are concerned with patients with respiratory complaints. Surprisingly there are unique problems in the residents of our State. The full impact of problems known to cause respiratory illnesses, such as asbestosis, will not be known for years to come. Other problems such as the effect of sugarcane burning are just now being identified and may show a parallel to the inhalation of asbestos dust. VOG may be simply an irritant or it may explain in part the high incidence of asthma in our State. Clearly more work needs to be done to explain the pathophysiology, the risk and possible treatment for the consequences on people of these putative toxic substances

Decide : agents controlling a BHS of an airport hub

It is an ingrown fsar to most travelers, frequent or not, to lose their baggage while flying from one destination to another, but if you take a look behind the scene you will experience a system with a complexity unlike most others. The baggage handling system (BHS) of an airport is just one link in a Song chain of processes your bag is going through. The BHS stretches from check-in or unloading of a plane on to the BHS (connecting flights), to it is collected at the gate and transferred to your flight. The conventional control software use a strategy primarily based on a shortest path algorithm, not taking into account dynamical changes or utilizing less packed areas of the system to increase capacity. We changed that perspective towards a ecentralized multi-agent based solution by developing strongty collaborating agents, to replace the original control software. The hierarchy of agents horizontally spans the system through local agents capable of altering the flow of totes, and vertica!ly through mediator agents, which have a global perspective andsupport decisions ofthe locoi autonomous agents. The local agents monitors their own local neighborhood for rising queues and other delaying factors, which aggregate to a status of the node, influencing the decision, of other agents trying to loute totes through this node. Interactions are handled as a combination of contract-nets, queries, and subscriber interaction schemes, which generalized the agent interfaces from the specific application. An agent-based approach not only improves robustness of the system, and utilize the entire BHS in n more convenient and dynamical way, it also include strategies for maximizing capacify of the system, which follows a work in-progress against capadty curve (WIPAC). In this paper we present the agent-based design of the control-software, and elaborate on the mutual colloboration compliant with the FIPA interaction schemes. We present ontologies used for sharing information and services among the agents as well as the results of our work for a major airport hub in Asia, and compare it against the traditional centralized strategies. We complete the paper by drawing same condusions and present ideas for future work