Most commons in hematology and oncology

Short list of most common conditions associated with hematology and oncology

High vitamin B12 level

Vitamin B12/cobalamin functions as an important co-enzyme in the human body and is essential forpurine and pyrimidine synthesis. Vitamin B12 deficiency is a very well recognized clinical entity but the conditions leading to elevated levels of vitamin B12 are generally not; hence the purpose of this article is to discuss such etiologies. Understanding the mechanisms will necessitate a brief review of vitamin B12 metabolism, presented below

5-HT2B Receptor-mediated Cardiac Valvulopathy

5-HT2B receptor agonism causes cardiac valvulopathy, a condition characterized by thickening of the heart valves and as a result, regurgitation of blood within the heart. The anti-obesity drug fenfluramine, which was originally prescribed as an anorectic, was withdrawn from the market due to causing cardiac valvulopathy. Fenfluramine, after metabolism by N-dealkylation, produces the metabolite norfenfluramine, which acts as a more potent valvulopathogen. The same was seen with MDMA (ecstasy), a popular drug of abuse, which is metabolized by N-dealkylation to produce MDA, a more potent valvulopathogen. Glennon and co-workers. studied a series of 2,5-dimethoxy-4- substituted phenylisopropylamines (DOX type) hallucinogens and determined their affinities at the three types of 5-HT2 receptors. A high correlation was found between the affinities of these molecules at 5-HT2A and 5-HT2B receptors. Therefore, these hallucinogens have a high possibility of causing valvulopathy, which gives rise to a new class of valvulopathogens. Since certain hallucinogens have the common phenylisopropylamine structural scaffold as that of MDA and norfenfluramine, we conducted 3D-QSAR studies to identify the common structural features of these molecules that are responsible for their high affinities. We were unable to obtain a suitable CoMFA and CoMSIA model for 5-HT2B receptors, but we were able to obtain an internally and externally validated model for 5-HT2A receptor affinities which indicated the hydrophobicity of the substituent at the 4- position was essential for high affinity. Following up with this evidence, we conducted a correlation analysis for the hydrophobicity (π-value) of the 4-position substituent and found a positive correlation between the π-value and the affinity of the molecules. The same results were not observed for the volume of the substituents. We docked the molecules into the 5-HT2B receptor and successfully generated models of the putative interactions made by the DOX molecules and the receptor. In order to compare their binding modes with respect to known valvulopathogens, we also generated models for norfenfluramine and MDA. Our docking results revealed that DOX molecules bind in a more or less similar manner to valvulopathogens MDA and norfenfluramine. Ours is the first in silico model developed for the potent valvulopathogen MDA and the hallucinogenic DOX series of molecules

Development of an inexpensive guidance system for agricultural purposes

Robotics is a rapidly growing technology and robots have pervaded into most of the industries. Robotics and automation are designed to remove the human factor from the labor intensive and monotonous work and thereby decrease the associated costs. The application of robotics to agriculture is fairly recent. Robotic applications in agriculture vary from autonomous row-guidance tractors to fruit picking robots. Similarly, soil testing and soil sampling is one area in agriculture where automation of tasks and the employment of an autonomous robot would be of great use to consultants and farmers employing site specific farming techniques. Soil testing is an important part of farming used to determine the average nutrient status in a field and to obtain a measure of nutrient availability in the field. Fertilizers and other nutrients are applied to the fields based on different soil tests. Site specific farming is greatly dependent on soil testing and can result in increased yield, reduced cost and reduced water pollution. Soil testing requires a lot of soil samples and soil sampling is a time consuming, laborious process and expensive process. Most of the consultants employing site specific techniques use ATVs to get around large fields when sampling. The development of an autonomous guidance system for an ATV to perform soil sampling would be greatly beneficial to them. Labor costs would be significantly reduced and the operators would be subjected to fewer environmental elements. The use of ATVs ensures that no extra capital is needed to buy a vehicle. The use of a small vehicle like an ATV also causes less soil compaction. A WAAS enabled Differential GPS with accuracies to within 9.84 feet was used as the position sensor. Pocket PCs are more portable than a laptop computer and are more suitable for farm conditions. Shape files were used to provide the sampling points as input to the guidance program. A guidance program was made to operate on a PDA and provide guidance instructions. A microprocessor was programmed to read the guidance instructions and actuate the different components like throttle and steering. Tests were conducted to test the accuracy and consistency of the system. The offsets of each stop point from the test point were documented and analyzed. The results indicated that the system was as accurate as the GPS used for guidance. They also indicated that a guidance system can be realized with the use of very few components and an accuracy needed for soil sampling can be achieved. Avoidance routines for obstacles within the field were indicated as future developments

Update in juvenile myositis.

This update on childhood idiopathic inflammatory myopathies (IIMs) reviews recent progress in the field of translational science and clinical research over the past 12-18 months

ASH choosing wisely

The Choosing Wisely(R) campaign challenges medical societies to identify 5 tests, procedures, or treatments within each specialty's clinical domain that are offered to patients despite an absence of evidence demonstrating benefit or, in some cases, despite evidence demonstrating disutility or harm

The role of Th17 cells in juvenile idiopathic arthritis

Autoimmune arthritis in childhood, know as juvenile idiopathic arthritis (JIA), has a heterogeneity, ranging from monoarthritis to recalcitrant polyarthritis, making it a model disease in which to study immuno-regulation. Regulatory T cells, key players in peripheral immune homeostasis are enriched in the joints of JIA patients, particularly those with mild arthritis. To test the factors that lead to this enrichment, Treg trafficking was examined in the context of JIA. Synovial Treg showed enhanced chemotaxis to the inflammatory chemokine CCL5, widely detectable within the joint, when compared to Treg from peripheral blood. The trafficking of a related, but highly inflammatory T cell subset, Th17 cells, was also investigated. Th17 cells play a dominant role in murine models of arthritis, yet their contribution to human disease is unknown. The data presented here, showed that IL-17+ CD4 T cells were enriched in the joints of JIA patients, by a CCR6 dependent mechanism and importantly, their frequency correlated with the severity of disease course. The majority of synovial IL-17+ CD4 T cells expressed a cytokine and chemokine receptor phenotype intermediate between Th17 and Th1. Here it was shown that these cells (Th17/1) expressed high levels of both Th17 and Th1 specific transcription factors, RORC2 and T-bet. Modelling the generation of Th17/1 in vitro, Th17 cells ‘converted’ to Th17/1 under conditions which mimicked the disease site, namely low TGFβ and high IL-12 levels. Using CD161, a human Th17 marker, it was shown that synovial Th17/1 cells, and unexpectedly, a large proportion of Th1 cells expressed CD161. This study provided evidence to support a Th17 origin for Th1 cells expressing CD161. In vitro, Th17 cells which converted to a Th1 phenotype maintained CD161 expression, whilst in the joint CD161+ Th1 cells shared features with Th17 cells, with shared T cell receptor clonality and expression of RORC2, although they were IL-17 negative. We propose that Th17 cells may 'convert' to Th17/1 and Th1 cells in human arthritis. Therefore therapies targeting the induction of Th17 cells could also attenuate the Th17/1 and Th1 effector populations within the inflamed joint

A modular positive feedback-based gene amplifier

<p>Abstract</p> <p>Background</p> <p>Positive feedback is a common mechanism used in the regulation of many gene circuits as it can amplify the response to inducers and also generate binary outputs and hysteresis. In the context of electrical circuit design, positive feedback is often considered in the design of amplifiers. Similar approaches, therefore, may be used for the design of amplifiers in synthetic gene circuits with applications, for example, in cell-based sensors.</p> <p>Results</p> <p>We developed a modular positive feedback circuit that can function as a genetic signal amplifier, heightening the sensitivity to inducer signals as well as increasing maximum expression levels without the need for an external cofactor. The design utilizes a constitutively active, autoinducer-independent variant of the quorum-sensing regulator LuxR. We experimentally tested the ability of the positive feedback module to separately amplify the output of a one-component tetracycline sensor and a two-component aspartate sensor. In each case, the positive feedback module amplified the response to the respective inducers, both with regards to the dynamic range and sensitivity.</p> <p>Conclusions</p> <p>The advantage of our design is that the actual feedback mechanism depends only on a single gene and does not require any other modulation. Furthermore, this circuit can amplify any transcriptional signal, not just one encoded within the circuit or tuned by an external inducer. As our design is modular, it can potentially be used as a component in the design of more complex synthetic gene circuits.</p