Overexpression of MyrAkt1 in endothelial cells leads to erythropoietin- and BMP4-independent splenic erythropoiesis in mice.

Under steady state conditions, erythropoiesis occurs in the bone marrow. However, in mice, stress or tissue hypoxia results in increased erythropoiesis in the spleen. There is increasing evidence that the hematopoietic microenvironment, including endothelial cells, plays an important role in regulating erythropoiesis.

Excited-state relaxation of ruthenium polypyridyl compounds relevant to dye-sensitized solar cells.

Remarkably little is known about metal-to-ligand charge transfer (MLCT) excited-state relaxation pathways for the ruthenium polypyridyl compounds commonly utilized in dye-sensitized solar cells. Herein, we report variable-temperature photoluminescence studies of compounds of the general type cis-Ru(LL)2(X)2, where LL is a bipyridyl ligand and X is CN(-) or NCS(-), and contrast them with the well-known Ru(bpy)3(2+) and Os(bpy)3(2+), where bpy is 2,2'-bipyridine, to identify relaxation pathways. In fluid acetonitrile and propylene carbonate solutions, excited-state relaxation was found to obey a first-order kinetic model.

Efficacy and toxicity of a CD22-targeted antibody-saporin conjugate in a xenograft model of non-Hodgkin's lymphoma.

Antibody drug conjugates (ADCs) can deliver potent drugs to cancer cells by employing the specificity of monoclonal antibodies (mAbs). ADCs have demonstrated significant anticancer activity and, in 2011, brentuximab vedotin has been approved by the FDA for the treatment of Hodgkin's and anaplastic large cell lymphomas. CD22 is an ideal target for ADC against B-cell malignancies because of its lineage-specific expression and rapid internalization upon antibody binding.

Three genes involved in the oxidative burst are closely linked in the genome of the snail, Biomphalaria glabrata.

Allelic variation at the Cu-Zn superoxide dismutase (SOD1) locus has been shown to be associated with resistance of the snail, Biomphalaria glabrata, to infection by the trematode parasite, Schistosoma mansoni. SOD1 catalyses the production of hydrogen peroxide, a known cytotoxic component of the oxidative burst used in defence against pathogens. In our laboratory population of B.

RhoB differentially controls Akt function in tumor cells and stromal endothelial cells during breast tumorigenesis.

Tumors are composed of cancer cells but also a larger number of diverse stromal cells in the tumor microenvironment. Stromal cells provide essential supports to tumor pathophysiology but the distinct characteristics of their signaling networks are not usually considered in developing drugs to target tumors. This oversight potentially confounds proof-of-concept studies and increases drug development risks.

Efficacy of a CD22-targeted antibody-saporin conjugate in a xenograft model of precursor-B cell acute lymphoblastic leukemia.

Targeted therapies, such as those using imatinib and rituximab, have revolutionized the treatment of Philadelphia chromosome-positive and CD20-positive acute lymphoblastic leukemia (ALL) respectively, yet these therapies are effective in only a subset of patients and remission is generally not durable. The next generation of targeted therapies includes the use of antibodies conjugated to potent cytotoxic agents and are classified as antibody drug conjugates (ADC). For B-lineage ALL, CD22 is an ideal target for ADC therapy because it is expressed on the majority of B-lineage ALL cells and because antibody binding mediates receptor internalization.

CD22 antigen is broadly expressed on lung cancer cells and is a target for antibody-based therapy.

Most patients with lung cancer still die from their disease, necessitating additional options to improve treatment. Here, we provide evidence for targeting CD22, a cell adhesion protein known to influence B-cell survival that we found is also widely expressed in lung cancer cells. In characterizing the antitumor activity of an established anti-CD22 monoclonal antibody (mAb), HB22.

The role of lysyl oxidase family members in the stabilization of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are a major cause of morbidity and mortality in the United States today. We employed a model for AAA development using apolipoprotein E knock out mice fed a high-fat diet and treated with ANG II and β-aminopropionitrile (β-APN) for 4 wk. ANG II induces hypertension and atherosclerotic disease, whereas β-APN inhibits the activity of the lysyl oxidase/ lysyl oxidase-like protein (LOX/LOXL) family members.

Soft tissue sarcoma, version 2.2012: featured updates to the NCCN guidelines.

The major changes to the 2012 and 2011 NCCN Guidelines for Soft Tissue Sarcoma pertain to the management of patients with gastrointestinal stromal tumors (GISTs) and desmoid tumors (aggressive fibromatosis). Postoperative imatinib following complete resection for primary GIST with no preoperative imatinib is now included as a category 1 recommendation for patients with intermediate or high risk of recurrence. The panel also reaffirmed the recommendation for preoperative use of imatinib in patients with GISTs that are resectable with negative margins but associated with significant surgical morbidity.

'I'm not doing this for me': mothers' accounts of creating smoke-free homes.

This article explores mothers' narratives of changing home smoking behaviours after participating in an intervention (Reducing Families' Exposure to Smoking in the Home [REFRESH]) aimed at reducing families' exposure to secondhand smoke (SHS) in homes in Scotland. An analysis of qualitative findings illuminates quantitative changes in levels of SHS exposure. Prospective quantitative and qualitative data were drawn from 21 smoking mothers with at least one child under 6 years.

Regulators of skeletal development: a cluster analysis of 206 bone tumors reveals diagnostically useful markers.

The molecules Indian hedgehog (IHH), SP7 (also known as osterix), sex-determining region Y-box 9 (SOX9), runt-related transcription factor 2 (RUNX2) and TWIST1 regulate the normal differentiation of osteo- and chondrogenic cells from precursors during skeletal development and remodeling. The aberrant function of the same molecules has been implicated in the pathogenesis of bone tumors. Preliminary studies suggest that antibodies against these molecules have practical, diagnostic or prognostic utility in tumors.

Monkey see, monkey do: contagious itch in nonhuman primates.

"Contagious itch" has been anecdotally reported and recently confirmed in a controlled setting in humans. Here, we investigated in adult rhesus macaques whether 'contagious itch' occurs spontaneously in monkeys. In a first experiment, the latency to scratch following cage-mate scratching was observed in pair-housed adult rhesus macaques.

REFRESH--reducing families' exposure to secondhand smoke in the home: a feasibility study.

Objective: To study a novel intervention (REFRESH) aimed at reducing children's exposure to secondhand smoke (SHS) in their homes.

Design: A randomised feasibility study.

Setting: Aberdeen City and Aberdeenshire.

SIV-induced impairment of neurovascular repair: a potential role for VEGF.

Peripheral nerves and blood vessels travel together closely during development but little is known about their interactions post-injury. The SIV-infected pigtailed macaque model of human immunodeficiency virus (HIV) recapitulates peripheral nervous system pathology of HIV infection. In this study, we assessed the effect of SIV infection on neurovascular regrowth using a validated excisional axotomy model.

Disulfide cross-linked micelles for the targeted delivery of vincristine to B-cell lymphoma.

Vincristine (VCR) is a potent anticancer drug, but its clinical efficacy is limited by neurotoxicity. The field of drug delivery may provide an opportunity to increase the therapeutic index of VCR by delivering the drug specifically to tumor sites while sparing normal tissue. We have recently developed a telodendrimer (PEG(5k)-Cys(4)-L(8)-CA(8)) capable of forming disulfide cross-linked micelles (DCMs) which can encapsulate a variety of chemotherapeutics.

Factors influencing exposure to secondhand smoke in preschool children living with smoking mothers.

Introduction: The health effects on young children of exposure to secondhand smoke (SHS) are well described. Recent work suggests that over one quarter of school-aged children in Scotland are regularly exposed to SHS in the home. The study was designed to describe SHS exposure in preschool children whose mothers smoked and identify factors that influence exposure.

Physiological sex steroid replacement in premature ovarian failure: randomized crossover trial of effect on uterine volume, endometrial thickness and blood flow, compared with a standard regimen.

Background: Premature ovarian failure (POF) is currently managed by non-physiological sex steroid regimens which are inadequate at optimizing uterine characteristics. Previous short-term studies have demonstrated some benefits of a sex steroid replacement (SSR) regimen devised to replicate the physiological cycle. This study aimed to directly compare the effects of longer-term administration of physiological SSR (pSSR) and standard SSR (sSSR) regimens on the uterine volume, blood flow and endometrial thickness (ET) in women with POF.

The HB22.7 Anti-CD22 monoclonal antibody enhances bortezomib-mediated lymphomacidal activity in a sequence dependent manner.

Most non-Hodgkin's lymphomas (NHL) initially respond to chemotherapy, but relapse is common and treatment is often limited by chemotherapy-related toxicity. Bortezomib, is a highly selective proteasome inhibitor with anti-NHL activity; it is currently FDA approved for second-line treatment of mantle cell lymphoma (MCL). Bortezomib exerts its activity in part through the generation of reactive oxygen species (ROS) and also by the induction of apoptosis.

Aseptic failure: how does the Compress(®) implant compare to cemented stems?

Background: Failure of endoprosthetic reconstruction with conventional stems due to aseptic loosening remains a challenge for maintenance of limb integrity and function. The Compress(®) implant (Biomet Inc, Warsaw, IN, USA) attempts to avoid aseptic failure by means of a unique technologic innovation. Though the existing literature suggests survivorship of Compress(®) and stemmed implants is similar in the short term, studies are limited by population size and followup duration.

RhoB deficiency in thymic medullary epithelium leads to early thymic atrophy.

RhoB, a member of the Rho subfamily of small GTPases, mediates diverse cellular functions, including cytoskeletal organization, cell transformation and vesicle trafficking. The thymus undergoes progressive decline in its structure and function after puberty. We found that RhoB was expressed in thymic medullary epithelium.

Time-resolved analysis of coronary vein motion and cross-sectional area.

Purpose: To quantify periods of low motion and cross-sectional area changes of the coronary veins during the cardiac cycle for planning magnetic resonance coronary venograms (MRCV).

Materials And Methods: Images were acquired from 19 patients with coronary artery disease (CAD) and 13 patients scheduled for cardiac resynchronization therapy (CRT). The displacement and cross-sectional area of the coronary sinus was tracked, and periods of low motion were defined as consecutive time points during which the position of the coronary sinus remained within a 0.

Patellar metastatic melanoma in a 13-year-old boy.

The incidence of melanoma in US adults is approximately 1.5 per million, with 2% to 5% of patients developing metastatic disease. In children, melanoma is distinctly uncommon, and metastatic disease occurs even more seldom.

Off-pump and on-pump coronary artery bypass grafting are associated with similar graft patency, myocardial ischemia, and freedom from reintervention: long-term follow-up of a randomized trial.

Background: The Surgical Management of Arterial Revascularization Therapies trial was conceived to rigorously compare completeness of revascularization, clinical outcomes and resource utilization in unselected patients referred for elective, primary coronary artery bypass grafting randomly assigned to undergo off-pump (OPCAB) or conventional on-pump coronary artery bypass grafting using cardiopulmonary bypass (CPB). The goal of this follow-up study was to compare long-term survival, graft patency, myocardial ischemia, and clinical outcomes among survivors who volunteered to return for clinical evaluation and imaging studies.

Methods: Two hundred unselected patients with multivessel coronary artery disease were randomly assigned to OPCAB or CPB coronary artery bypass grafting between March 2000 and August 2001.

Impaired neurovascular repair in subjects with diabetes following experimental intracutaneous axotomy.

Diabetic complications and vascular disease are closely intertwined. Diabetes mellitus is a well-established risk factor for both large and small vessel vascular changes, and conversely other vascular risk factors confer increased risk for diabetic complications such as peripheral neuropathy, nephropathy and retinopathy. Furthermore, axons and blood vessels share molecular signals for purposes of navigation, regeneration and terminal arborizations.