Transcriptome analyses reveal common immune system dysregulation in PAH patients and -deficient rats.

Pulmonary arterial hypertension (PAH) is a severe disease caused by progressive distal pulmonary artery obstruction. One cause of PAH are loss-of-function mutations in the potassium channel subfamily K member 3 (KCNK3). KCNK3 encodes a two-pore domain potassium channel, which is crucial for pulmonary circulation homeostasis.

Role of KCNK3 Dysfunction in Dasatinib-associated Pulmonary Arterial Hypertension and Endothelial Cell Dysfunction.

Pulmonary arterial (PA) hypertension (PAH) is a severe cardiopulmonary disease that may be triggered by exposure to drugs such as dasatinib or facilitated by genetic predispositions. The incidence of dasatinib-associated PAH is estimated at 0.45%, suggesting individual predispositions.

Expression of complement C3, C5, C3aR and C5aR1 genes in resting and activated CD4 T cells.

Complement activation is traditionally thought to occur in the extracellular space. However, it has been suggested that complement proteins are activated and function at additional locations. T cells contain intracellular stores of C3 and C5 that can be cleaved into C3a and C5a and bind to intracellular receptors, which have been shown to be of vital importance for the differentiation and function of these cells.

ERG promotes the maintenance of hematopoietic stem cells by restricting their differentiation.

The balance between self-renewal and differentiation is crucial for the maintenance of hematopoietic stem cells (HSCs). Whereas numerous gene regulatory factors have been shown to control HSC self-renewal or drive their differentiation, we have relatively few insights into transcription factors that serve to restrict HSC differentiation. In the present work, we identify ETS (E-twenty-six)-related gene (ERG) as a critical factor protecting HSCs from differentiation.

TGIF1 is a negative regulator of MLL-rearranged acute myeloid leukemia.

Members of the TALE (three-amino-acid loop extension) family of atypical homeodomain-containing transcription factors are important downstream effectors of oncogenic fusion proteins involving the mixed lineage leukemia (MLL) gene. A well-characterized member of this protein family is MEIS1, which orchestrates a transcriptional program required for the maintenance of MLL-rearranged acute myeloid leukemia (AML). TGIF1/TGIF2 are relatively uncharacterized TALE transcription factors, which, in contrast to the remaining family, have been shown to act as transcriptional repressors.

Initiation of MLL-rearranged AML is dependent on C/EBPα.

MLL-fusion proteins are potent inducers of oncogenic transformation, and their expression is considered to be the main oncogenic driving force in ∼10% of human acute myeloid leukemia (AML) patients. These oncogenic fusion proteins are responsible for the initiation of a downstream transcriptional program leading to the expression of factors such as MEIS1 and HOXA9, which in turn can replace MLL-fusion proteins in overexpression experiments. To what extent MLL fusion proteins act on their own during tumor initiation, or if they collaborate with other transcriptional regulators, is unclear.

Patients with malignant hematological disorders treated on a palliative care unit: prognostic impact of clinical factors.

A reliable estimation of prognosis in patients receiving palliative care is desirable in order to facilitate clinical decision finding. For patients with advanced hematological malignancies, only few data are available to estimate prognosis of the individual's remaining life span. Here, we sought to investigate potential clinical prognostic parameters in patients with hematological malignancies admitted to a palliative care unit.

Anti-Escherichia coli asparaginase antibody levels determine the activity of second-line treatment with pegylated E coli asparaginase: a retrospective analysis within the ALL-BFM trials.

Hypersensitivity reactions limit the use of the antileukemic enzyme asparaginase (ASE). We evaluated Ab levels against Escherichia coli ASE and ASE activity in 1221 serum samples from 329 patients with acute lymphoblastic leukemia who had received ASE treatment according to the ALL-BFM 2000 or the ALL-REZ BFM 2002 protocol for primary or relapsed disease. ASE activity during first-line treatment with native E coli ASE and second-line treatment with pegylated E coli ASE was inversely related to anti-E coli ASE Ab levels (P < .

A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia.

Chromosomal translocations of transcription factors generating fusion proteins with aberrant transcriptional activity are common in acute leukemia. In acute promyelocytic leukemia (APL), the promyelocytic leukemia-retinoic-acid receptor alpha (PML-RARA) fusion protein, which emerges as a consequence of the t(15;17) translocation, acts as a transcriptional repressor that blocks neutrophil differentiation at the promyelocyte (PM) stage. In this study, we used publicly available microarray data sets and identified signatures of genes dysregulated in APL by comparison of gene expression profiles of APL cells and normal PMs representing the same stage of differentiation.

Characterization of an antagonistic switch between histone H3 lysine 27 methylation and acetylation in the transcriptional regulation of Polycomb group target genes.

Polycomb group (PcG) proteins are transcriptional repressors, which regulate proliferation and cell fate decisions during development, and their deregulated expression is a frequent event in human tumours. The Polycomb repressive complex 2 (PRC2) catalyzes trimethylation (me3) of histone H3 lysine 27 (K27), and it is believed that this activity mediates transcriptional repression. Despite the recent progress in understanding PcG function, the molecular mechanisms by which the PcG proteins repress transcription, as well as the mechanisms that lead to the activation of PcG target genes are poorly understood.

Cetuximab-based treatment of metastatic anal cancer: correlation of response with KRAS mutational status.

Background: No standard chemotherapy regimen can be defined for patients with metastatic squamous cell carcinoma of the anus due to the low incidence of this disease and the high cure rate of localized tumors. Anal cancers universally express the epidermal growth factor receptor (EGFR) and KRAS mutations have not been reported in anal cancer thus far.

Methods: We report on 7 patients with metastatic anal cancer treated with cetuximab - a chimeric antibody against EGFR - on a compassionate use basis along with the results of KRAS mutational analysis.

Distribution of mucins and antimicrobial substances lysozyme and lactoferrin in the laryngeal subglottic region.

The subglottic region of the larynx is of high clinical relevance with regard to infections and malignancies. Little is known about the distribution of mucins and antimicrobial substances in this area. In this study, we have investigated the mucin distribution in the normal subglottis of the larynx.

A phase II study of capecitabine and irinotecan in combination with concurrent pelvic radiotherapy (CapIri-RT) as neoadjuvant treatment of locally advanced rectal cancer.

We sought to evaluate the efficacy and safety data of a combination regimen using weekly irinotecan in combination with capecitabine and concurrent radiotherapy (CapIri-RT) as neoadjuvant treatment in rectal cancer in a phase-II trial. Patients with rectal cancer clinical stages T3/4 Nx or N+ were recruited to receive irinotecan (50 mg m(-2) weekly) and capecitabine (500 mg m(-2) bid days 1-38) with a concurrent RT dose of 50.4 Gy.

Leukocytoclastic vasculitis and acute renal failure after influenza vaccination in an elderly patient with myelodysplastic syndrome.

Background: Influenza vaccination is recommended for individuals over 65 years of age and for all patients with chronic diseases who are at risk. Side effects which are seen in 1-10% of the vaccinated individuals are usually mild and consist of local reactions and constitutional symptoms. Since 1974, about 30 cases of vasculitis following influenza vaccination have been reported.

Pegylated liposomal doxorubicin and mitomycin C in combination with infusional 5-fluorouracil and sodium folinic acid in the treatment of advanced gastric cancer: results of a phase II trial.

Mitomycin C (MMC) in combination with infusional 5-fluorouracil (5-FU) is a well-tolerated active combination therapy for advanced gastric cancer. Pegylated liposomal doxorubicin (Caelyx) has been combined with this regimen in a phase I study exhibiting promising activity in patients with upper gastrointestinal tumors. In the present study, we investigated activity and tolerability of this three-drug regimen in patients with gastric cancer.

Capecitabine in combination with mitomycin C in patients with gastrointestinal cancer: results of an extended multicentre phase-I trial.

The aim of this study was to determine the dose-limiting toxicity (DLT) and establish the recommended dose for mitomycin C added every 3 weeks to the standard combination dose of capecitabine. Cohorts of at least three patients with pretreated gastrointestinal carcinoma received capecitabine 1000 mg m(-2) orally twice daily on days 1-14 plus i.v.

Pegylated liposomal doxorubicin in combination with mitomycin C, infusional 5-fluorouracil and sodium folinic acid. A phase-I-study in patients with upper gastrointestinal cancer.

Mitomycin C (MMC) in combination with infusional 5-fluorouracil (FU) plus folinic acid (FA) is an effective treatment for metastatic gastrointestinal cancer. Anthracyclines are commonly used in the treatment of upper gastrointestinal cancer. The aim of this study was to determine the maximum tolerated dose of liposomal, pegylated doxorubicin (Caelyx) in combination with infusional 5-FU/sodium FA and MMC.

Reduction of the individual cancer risk by physical exercise.

The great variety of different types of human malignancies and the equally variable individual history of physical activity militate against finding any simple relationship between the risk of developing cancer and physical activity. Due to an obvious lack of prospective randomized trials, any evidence for a correlation is currently based on cohort and case control studies. Furthermore, the study results are sometimes inconsistent, and only for selected cancers, the available data are sufficient to draw any conclusions, resulting in a level of evidence of 2-3 (level of recommendation 'B').

Treatment of a patient with advanced esophageal cancer with a combination of mitomycin C and capecitabine: activation of the thymidine phosphorylase as active principle?

Background: Both capecitabine, an oral prodrug of 5-fluorouracil (5-FU), and mitomycin C (MMC) have demonstrated activity as single agents in patients with gastrointestinal cancer. Furthermore, a combination of MMC with infusional 5-FU can induce tumor remission even in patients pretreated with 5-FU. Capecitabine and MMC act synergistically due to an upregulation of the thymidine phosphorylase activity by MMC in a human xenograft model.

Video streaming in nursing education: bringing life to online education.

Distance education is a standard form of instruction for many colleges of nursing. Web-based course and program content has been delivered primarily through text-based presentations such as PowerPoint slides and Web search activities. However, the rapid pace of technological innovation is making available more sophisticated forms of delivery such as video streaming.

Auer rod-like inclusions in multiple myeloma.

We report a case of IgA multiple myeloma, in which the plasma cells showed multiple azurophilic, Auer rod-like intracytoplasmic inclusions in May-Grünwald-Giemsa-stained marrow smears. Cytochemical stainings revealed a strong alpha-N-esterase activity of these inclusions, whereas the reactions for peroxidase, Sudan black, chloroacetate esterase, and PAS were negative. Immunostaining verified IgA-kappa inside the plasma cells.

Genomic anatomy of the specific reciprocal translocation t(15;17) in acute promyelocytic leukemia.

The genomic breakpoints in the t(15;17)(q22;q21), associated with acute promyelocytic leukemia (APL), are known to occur within three different PML breakpoint cluster regions (bcr) on chromosome 15 and within RARA intron 2 on chromosome 17; however, the precise mechanism by which this translocation arises is unclear. To clarify this mechanism, we (i). assembled the sequence of RARA intron 2, (ii).