BRAF signals to pro-apoptotic BIM to enhance AraC cytotoxicity induced in AML cells by Vitamin D-based differentiation agents.

Vitamin D has so far not fulfilled its early promise as an antineoplastic agent, in spite of compelling in vitro data. With the aim of bringing vitamin D or its derivatives (VDDs) effectively to the clinic, we developed a two-pronged approach. First, by adding the plant-derived Carnosic Acid (CA) to a vitamin D2 derivative Doxercalciferol we increased its differentiation potency without increasing it hypercalcemic properties.

Characterization of urge to cough and cough symptoms associated with the common cold: results of a US internet survey.

Objectives: Our knowledge of cough physiology is limited despite years of study. Even less is known about the sensation of urge to cough. Given that limited clinical data are available about urge to cough and cough attributes during a common cold, we sought to gain insights into experiences and perceptions related to these symptoms.

Differential Expression of IR-A, IR-B and IGF-1R in Endometrial Physiology and Distinct Signature in Adenocarcinoma.

Context: Type 2 diabetes and obesity are risk factors for endometrial hyperplasia and cancer, suggesting that hyperinsulinemia contributes to pathogenesis. Insulin action through insulin receptor (IR) splice variants IR-A and IR-B regulates cellular mitogenesis and metabolism, respectively.

Objective: We hypothesized that IR-A and IR-B are differentially regulated in normal endometrium, according to mitogenic and metabolic requirements through the menstrual cycle, as well as in endometrial hyperplasia and cancer.

Brain lipid sensing and the neural control of energy balance.

Fatty acid (FA) -sensitive neurons are present in the brain, especially the hypothalamus, and play a key role in the neural control of energy and glucose homeostasis including feeding behavior, secretion insulin and action. Subpopulations of neurons in the arcuate and ventromedial hypothalamic nuclei are selectively either activated or inhibited by FA. Molecular effectors of these FA effects include ion channels such as chloride, potassium or calcium.

Enhancement of arabinocytosine (AraC) toxicity to AML cells by a differentiation agent combination.

Arabinocytosine (AraC, also known as cytarabine) is one of the mainstays of AML therapy, but like other DNA damaging therapeutic agents it is rarely curative by itself. There is an emerging realization that the therapeutic outcomes may be improved by combining AraC with other compounds. Here we report that the addition of a differentiating agent combination immediately following AraC damage to AML blasts, selectively increases the cell kill.

Treatment of Patellar Tendinopathy Refractory to Surgical Management Using Percutaneous Ultrasonic Tenotomy and Platelet-Rich Plasma Injection: A Case Presentation.

Chronic proximal patellar tendinopathy is a common condition in sports medicine that may be refractory to nonoperative treatments, including activity modification, medications, and comprehensive rehabilitation. Percutaneous ultrasonic tenotomy is a recently developed technique designed to cut and debride tendinopathic tissue, thus promoting pain relief and functional recovery. We present a case of a collegiate athlete with chronic proximal patellar tendinopathy who was effectively treated with percutaneous ultrasonic tenotomy after not responding to extensive nonoperative treatment, surgical debridement, and platelet-rich plasma injections.

Evolution of genetic techniques: past, present, and beyond.

Genetics is the study of heredity, which means the study of genes and factors related to all aspects of genes. The scientific history of genetics began with the works of Gregor Mendel in the mid-19th century. Prior to Mendel, genetics was primarily theoretical whilst, after Mendel, the science of genetics was broadened to include experimental genetics.

Vitamin D Control of Hematopoietic Cell Differentiation and Leukemia.

It is now well known that in the mammalian body vitamin D is converted by successive hydroxylations to 1,25-dihydroxyvitamin D (1,25D), a steroid-like hormone with pleiotropic properties. These include important contributions to the control of cell proliferation, survival and differentiation, as well as the regulation of immune responses in disease. Here, we present recent advances in current understanding of the role of 1,25D in myelopoiesis and lymphopoiesis, and the potential of 1,25D and analogs (vitamin D derivatives; VDDs) for the control of hematopoietic malignancies.

The MAPK ERK5, but not ERK1/2, inhibits the progression of monocytic phenotype to the functioning macrophage.

Intracellular signaling pathways present targets for pharmacological agents with potential for treatment of neoplastic diseases, with some disease remissions already recorded. However, cellular compensatory mechanisms usually negate the initial success. For instance, attempts to interrupt aberrant signaling downstream of the frequently mutated ras by inhibiting ERK1/2 has shown only limited usefulness for cancer therapy.

Molecular mechanisms mediating mitochondrial dynamics and mitophagy and their functional roles in the cardiovascular system.

Mitochondria are essential organelles that produce the cellular energy source, ATP. Dysfunctional mitochondria are involved in the pathophysiology of heart disease, which is associated with reduced levels of ATP and excessive production of reactive oxygen species. Mitochondria are dynamic organelles that change their morphology through fission and fusion in order to maintain their function.

Calcific aortic valve disease: a consensus summary from the Alliance of Investigators on Calcific Aortic Valve Disease.

Calcific aortic valve disease (CAVD) is increasingly prevalent worldwide with significant morbidity and mortality. Therapeutic options beyond surgical valve replacement are currently limited. In 2011, the National Heart Lung and Blood Institute assembled a working group on aortic stenosis.

Interplay of oxidative, nitrosative/nitrative stress, inflammation, cell death and autophagy in diabetic cardiomyopathy.

Diabetes is a recognized risk factor for cardiovascular diseases and heart failure. Diabetic cardiovascular dysfunction also underscores the development of diabetic retinopathy, nephropathy and neuropathy. Despite the broad availability of antidiabetic therapy, glycemic control still remains a major challenge in the management of diabetic patients.

Lipid sensing in the brain and regulation of energy balance.

Nutrient-sensitive neurons [to glucose and fatty acids (FAs)] are present at many sites throughout the brain, including the hypothalamus and brain stem, and play a key role in the neural control of energy and glucose homoeostasis. Through their neuronal output, FAs can modulate feeding behaviour as well as insulin secretion and activity. Central administration of oleate, for example, inhibits food intake and glucose production in rats.

Reducing radiation dose in body CT: a practical approach to optimizing CT protocols.

Objective: The purpose of this article is to describe an approach to protocol modifications in body CT to reduce patient radiation exposure while maintaining image quality and to illustrate the effects of these modifications.

Conclusion: One should become proficient in interpreting the CT dose report, adjusting CT technical parameters, and applying focused collimation. The goal is to intelligently use CT to answer the question of clinical concern in the most dose-efficient manner.

Reducing radiation dose in body CT: a primer on dose metrics and key CT technical parameters.

Objective: The purpose of this article is to describe how to interpret radiation dosi-metric data available on a body CT dose report and to explain the effects of key operator-chosen CT parameters on patient radiation dose.

Conclusion: To apply dose reduction strategies in body CT, radiologists must understand the information contained in the CT dose report and know the effects of key CT technical parameters on patient radiation exposure.

The essential polysome-associated RNA-binding protein RBP42 targets mRNAs involved in Trypanosoma brucei energy metabolism.

RNA-binding proteins that target mRNA coding regions are emerging as regulators of post-transcriptional processes in eukaryotes. Here we describe a newly identified RNA-binding protein, RBP42, which targets the coding region of mRNAs in the insect form of the African trypanosome, Trypanosoma brucei. RBP42 is an essential protein and associates with polysome-bound mRNAs in the cytoplasm.

Use of recombination-mediated genetic engineering for construction of rescue human cytomegalovirus bacterial artificial chromosome clones.

Bacterial artificial chromosome (BAC) technology has contributed immensely to manipulation of larger genomes in many organisms including large DNA viruses like human cytomegalovirus (HCMV). The HCMV BAC clone propagated and maintained inside E. coli allows for accurate recombinant virus generation.

Intimal tears in thoracic aortic dissection: appearance on MDCT with virtual angioscopy.

Objective: The location, number, size, and configuration of intimal tears in aortic dissection have important therapeutic and prognostic implications. Planning of procedures to treat complications of aortic dissection may require precise delineation of the intimal tears. The purpose of this article is to illustrate the ability of MDCT using multiplanar image reformatting and virtual angioscopy to depict the location and appearance of intimal tears and fenestrations within dissection flaps in cases of thoracic aortic dissection.

Terminal 14q deletion with unbalanced t(Y;14)(q12;q32) translocation.

Terminal deletions of chromosome 14q are very rarely reported. Schneider et al. (2008) reviewed about 20 cases of 14q32 region deletion in a previous article and only three of the cases involved autosomal translocations; however, no sex chromosome translocations were reported.

Kaposi's sarcoma-associated herpesvirus Rta tetramers make high-affinity interactions with repetitive DNA elements in the Mta promoter to stimulate DNA binding of RBP-Jk/CSL.

Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]) is the etiologic agent of Kaposi's sarcoma (KS) and lymphoproliferative diseases. We previously demonstrated that the KSHV lytic switch protein Rta stimulates DNA binding of the cellular RBP-Jk/CSL protein, the nuclear component of the Notch pathway, on Rta target promoters. In the current study, we define the promoter requirements for formation of transcriptionally productive Rta/RBP-Jk/DNA complexes.