The Impella 2.5 L for percutaneous mechanical circulatory support in severe humoral allograft rejection.

Heart transplant recipients who experience humoral rejection are at risk for hemodynamic instability. We report a case of a 64-year-old male with cardiogenic shock due to allograft rejection requiring mechanical support while undergoing intense immunosuppression. He underwent implantation of a micro-axial endovascular pump (Impella).

Phosphorylation of the mutant K303R estrogen receptor alpha at serine 305 affects aromatase inhibitor sensitivity.

We earlier identified a lysine to arginine transition at residue 303 (K303R) in estrogen receptor alpha (ERalpha) in invasive breast cancers, which confers resistance to the aromatase inhibitor (AI) anastrozole (Ana) when expressed in MCF-7 breast cancer cells. Here, we show that AI resistance arises through an enhanced cross talk of the insulin-like growth factor receptor-1 (IGF-1R)/insulin receptor substrate (IRS)-1/Akt pathway with ERalpha, and the serine (S) residue 305 adjacent to the K303R mutation has a key function in mediating this cross talk. The ERalpha S305 residue is an important site that modifies response to tamoxifen; thus, we questioned whether this site could also influence AI response.

Successful retrograde recanalization of a left anterior descending artery chronic total occlusion through a previously placed left anterior descending-to-diagonal artery stent.

Since the introduction of the retrograde technique, the success rate of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) has increased significantly in patients with suitable anatomy. To our knowledge, retrograde recanalization of a CTO from the abluminal side of a previously placed stent has not been reported. We describe a case of retrograde PCI of a mid left anterior descending (LAD) artery CTO through a previously placed proximal LAD stent which extended into the diagonal artery.

Bioinformatic analysis of gene sets regulated by ligand-activated and dominant-negative peroxisome proliferator-activated receptor gamma in mouse aorta.

Objective: Drugs that activate peroxisome proliferator-activated receptor (PPAR) gamma improve glucose sensitivity and lower blood pressure, whereas dominant-negative mutations in PPARgamma cause severe insulin resistance and hypertension. We hypothesize that these PPARgamma mutants regulate target genes opposite to those of ligand-mediated activation, and we tested this hypothesis on a genomewide scale.

Methods And Results: We integrated gene expression data in aorta specimens from mice treated with the PPARgamma ligand rosiglitazone with data from mice containing a globally expressed knockin of the PPARgamma P465L dominant-negative mutation.

Assessing persistence and long-range transport potential of current-use pesticides.

Despite the fact that current-use pesticides (CUP) have different chemical properties to first-generation organochlorine products, the long-term and long-range environmental behavior of these chemicals is still unclear. Data for 45 active ingredients of CUPs were collected, most of which originate from the results of simulation tests submitted for authorization. According to the Stockholm Convention on persistent organic pollutants (POPs), two of the 45 CUPs exceed both screening level criteria for persistence and long-range transport potential (LRTP).

Analysis of the impact of the Uruguay Round Agreements Act on pharmaceutical patents.

The Uruguay Round Agreements Act (URAA) was enacted by the United States Congress in 1994. The URAA provided substantial modifications to the framework for U.S.

Changes in left ventricular function and remodeling after myocardial infarction in hypothyroid rats.

It has been shown that hypothyroidism may lead to delayed wound healing after experimental myocardial infarction (MI) in rats and increased infarct size in dogs. However, the long-term effect of hypothyroidism on left ventricular (LV) remodeling after MI has not been determined. Adult female Sprague-Dawley rats with and without surgical thyroidectomy (TX) were used in the study.

STITCH 2: an interaction network database for small molecules and proteins.

Over the last years, the publicly available knowledge on interactions between small molecules and proteins has been steadily increasing. To create a network of interactions, STITCH aims to integrate the data dispersed over the literature and various databases of biological pathways, drug-target relationships and binding affinities. In STITCH 2, the number of relevant interactions is increased by incorporation of BindingDB, PharmGKB and the Comparative Toxicogenomics Database.

Accounting for redundancy when integrating gene interaction databases.

During the last years gene interaction networks are increasingly being used for the assessment and interpretation of biological measurements. Knowledge of the interaction partners of an unknown protein allows scientists to understand the complex relationships between genetic products, helps to reveal unknown biological functions and pathways, and get a more detailed picture of an organism's complexity. Being able to measure all protein interactions under all relevant conditions is virtually impossible.

Effects of low-dose intranasal (S)-ketamine in patients with neuropathic pain.

Background: NMDA receptors are involved in the development and maintenance of neuropathic pain. We evaluated the efficacy and safety of intranasal (S)-ketamine, one of the most potent clinically available NMDA receptor antagonists.

Methods: Sixteen patients with neuropathic pain of various origins were randomized into two treatment groups: (S)-ketamine 0.

Mrd1p is required for release of base-paired U3 snoRNA within the preribosomal complex.

In eukaryotes, ribosomes are made from precursor rRNA (pre-rRNA) and ribosomal proteins in a maturation process that requires a large number of snoRNPs and processing factors. A fundamental problem is how the coordinated and productive folding of the pre-rRNA and assembly of successive pre-rRNA-protein complexes is achieved cotranscriptionally. The conserved protein Mrd1p, which contains five RNA binding domains (RBDs), is essential for processing events leading to small ribosomal subunit synthesis.

Accelerated mammary maturation and differentiation, and delayed MMTVneu-induced tumorigenesis of K303R mutant ERalpha transgenic mice.

We identified a somatic mutation in estrogen receptor-alpha (ERalpha) in breast cancer causing a lysine to arginine transition (K303R) resulting in hypersensitivity to estrogen, altered associations with coactivators and corepressors and altered posttranslational modifications of ERalpha. We have developed a transgenic mouse expressing the K303R mutant ERalpha under control of the mouse mammary tumor virus (MMTV) promoter. At 4 months of age, K303R ERalpha transgenic animals demonstrate precocious alveolar budding compared with wild-type ERalpha transgenic mice or nontransgenic littermates.

Evidence for strain-induced local conductance modulations in single-layer graphene on SiO2.

Graphene has emerged as an electronic material that is promising for device applications and for studying two-dimensional electron gases with relativistic dispersion near two Dirac points. Nonetheless, deviations from Dirac-like spectroscopy have been widely reported with varying interpretations. Here we show evidence for strain-induced spatial modulations in the local conductance of single-layer graphene on SiO(2) substrates from scanning tunneling microscopic (STM) studies.

Androgen receptor overexpression induces tamoxifen resistance in human breast cancer cells.

Although the androgen receptor (AR) is a known clinical target in prostate cancer, little is known about its possible role in breast cancer. We have investigated the role of AR expression in human breast cancer in response to treatment with the antiestrogen tamoxifen. Resistance to tamoxifen is a major problem in treating women with breast cancer.

Expression of the K303R estrogen receptor-alpha breast cancer mutation induces resistance to an aromatase inhibitor via addiction to the PI3K/Akt kinase pathway.

Aromatase inhibitors (AI) are rapidly becoming the first choice for hormonal treatment of estrogen receptor-alpha (ERalpha)-positive breast cancer in postmenopausal women. However, de novo and acquired resistance frequently occurs. We have previously identified a lysine to arginine transition at residue 303 (K303R) in ERalpha in premalignant breast lesions and invasive breast cancers, which confers estrogen hypersensitivity and resistance to tamoxifen treatment.

Environmental fate and global distribution of polychlorinated biphenyls.

In recent decades, regulators, academia, and industry have all paid increasing attention to the crucial task of determining how xenobiotic exposures affect biota populations, communities, or entire ecosystems. For decades, PCBs have been recognized as important and potentially harmful environmental contaminants. The intrinsic properties of PCBs, such as high environmental persistence, resistance to metabolism in organisms, and tendency to accumulate in lipids have contributed to their ubiquity in environmental media and have induced concern for their toxic effects after prolonged exposure.

Predicting functionality of protein-DNA interactions by integrating diverse evidence.

Chromatin immunoprecipitation (ChIP-chip) experiments enable capturing physical interactions between regulatory proteins and DNA in vivo. However, measurement of chromatin binding alone is not sufficient to detect regulatory interactions. A detected binding event may not be biologically relevant, or a known regulatory interaction might not be observed under the growth conditions tested so far.

Detection and interpretation of expression quantitative trait loci (eQTL).

Analysis of expression quantitative trait loci (eQTL) provides a means for detecting transcriptional regulatory relationships at a genome-wide scale. Here we explain the eQTL analysis pipeline, we introduce publicly available tools for the statistical analysis, and we discuss issues that might complicate the eQTL mapping process. The detection and interpretation of eQTL requires careful consideration of a range of potentially confounding effects.

[Web-based electronic patient record as an instrument for quality assurance within an integrated care concept].

Objective: A prerequisite for integrated care programmes is the implementation of a communication network meeting quality assurance standards. Against this background the main objective of the integrated care project between the University Eye Hospital Erlangen and the health insurance company AOK Bayern was to evaluate the potential and the acceptance of a web-based electronic patient record in the context of cataract and retinal surgery.

Methods: Standardised modules for capturing pre-, intra- and post-operative data on the basis of clinical pathway guidelines for cataract- and retinal surgery have been developed.

The Paf1 complex is required for efficient transcription elongation by RNA polymerase I.

Regulation of RNA polymerase I (Pol I) transcription is critical for controlling ribosome synthesis. Most previous investigations into Pol I transcription regulation have focused on transcription initiation. To date, the factors involved in the control of Pol I transcription elongation are poorly understood.

Fully cross-linked and chemically patterned self-assembled monolayers.

Mechanically stable monolayers with chemically functional patterns are fabricated by the combination of spatially resolved chemical lithography with complete cross-linking of aromatic self-assembled monolayers (SAMs). The process starts with a local electron exposure of a SAM of 4'-nitro-1,1'-biphenyl-4-thiol that converts the nitro into amino groups and, additionally, generates a pattern of cross-linked and non cross-linked regions. In the next step, molecules in the non cross-linked regions are exchanged for 1,1'-biphenyl-4-thiol.

Decrease in adhesion molecules on polymorphonuclear leukocytes of patients with fibromyalgia.

Fibromyalgia (FM) is a chronic widespread pain condition in highly stressed humans. Because stress is known to modulate adhesion molecule expression, we determined L: -selectin (CD62L) and beta(2)-integrin (CD11b/CD18) expression on the surface of polymorphonuclear leukocytes in 22 patients with FM. As compared to age and sex-matched healthy controls, FM patients showed a significantly decreased expression of CD62L (p < 0.

White and gray matter abnormalities in the brain of patients with fibromyalgia: a diffusion-tensor and volumetric imaging study.

Objective: To use a combination of magnetic resonance diffusion-tensor imaging (MR-DTI) and MR imaging of voxel-based morphometry (MR-VBM) in patients with fibromyalgia syndrome (FMS) to determine microstructural and volume changes in the central neuronal networks involved in the sensory-discriminative and affective-motivational characteristics of pain, anxiety, memory, and regulation of the stress response.

Methods: Thirty female patients with FMS and 30 healthy female control subjects were studied. Predefined areas of the brain were measured for volume of gray matter by MR-VBM and for diffusivity and fractional anisotropy (FA) by MR-DTI.

Electron microscope visualization of RNA transcription and processing in Saccharomyces cerevisiae by Miller chromatin spreading.

The Miller chromatin spreading technique for electron microscopic visualization of gently dispersed interphase chromatin has proven extremely valuable for analysis of genetic activities in vivo. It provides a unique view of transcription and RNA processing at the level of individual active genes. The budding yeast Saccharomyces cerevisiae has also been an invaluable model system for geneticists and molecular biologists.