Amyloid-beta leads to impaired cellular respiration, energy production and mitochondrial electron chain complex activities in human neuroblastoma cells.

Evidence suggests that amyloid-beta (Abeta) protein is a key factor in the pathogenesis of Alzheimer's disease (AD) and it has been recently proposed that mitochondria are involved in the biochemical pathway by which Abeta can lead to neuronal dysfunction. Here we investigated the specific effects of Abeta on mitochondrial function under physiological conditions. Mitochondrial respiratory functions and energy metabolism were analyzed in control and in human wild-type amyloid precursor protein (APP) stably transfected human neuroblastoma cells (SH-SY5Y).

The future of targeted therapy approaches in melanoma.

Background: The past 30 years have seen little improvement in the survival of patients with stage IV melanoma. Following the discovery of activating BRAF mutations in most melanomas, a wealth of preclinical experimentation has validated the BRAF/MAPK pathway as an excellent therapeutic target in melanoma. Despite these encouraging results, early clinical trials on BRAF/MAPK inhibition have been disappointing.

Observation of unconventional quantum spin textures in topological insulators.

A topologically ordered material is characterized by a rare quantum organization of electrons that evades the conventional spontaneously broken symmetry-based classification of condensed matter. Exotic spin-transport phenomena, such as the dissipationless quantum spin Hall effect, have been speculated to originate from a topological order whose identification requires a spin-sensitive measurement, which does not exist to this date in any system. Using Mott polarimetry, we probed the spin degrees of freedom and demonstrated that topological quantum numbers are completely determined from spin texture-imaging measurements.

Towards a smart object network for clinical services.

Radio Frequency Identification (RFID) technology has become prevalent in logistics to support and optimize processes and numerous projects investigate its opportunities and challenges in the clinical context. However, most approaches are focused on one specific application using only a few possibilities of the technology. We describe the development of a smart object network to serve as a generic platform for various clinical services.

Rashba-type spin-orbit splitting of quantum well states in ultrathin Pb films.

A Rashba-type spin-orbit splitting is found for quantum well states formed in ultrathin Pb films on Si (111). The resulting momentum splitting is comparable to what is found for semiconductor heterostructures. The splitting shows no coverage dependency and the sign of the spin polarization is reversed compared to Rashba splitting in the Au(111) surface state.

Quantum Hall transition in real space: from localized to extended states.

Using scanning tunneling spectroscopy in an ultrahigh vacuum at low temperature (T=0.3 K) and high magnetic fields (B View Article and Find Full Text PDF

Inhibition of PI3K-AKT-mTOR signaling sensitizes melanoma cells to cisplatin and temozolomide.

In melanoma, the PI3K-AKT-mTOR (AKT) and RAF-MEK-ERK (MAPK) signaling pathways are constitutively activated and appear to play a role in chemoresistance. Herein, we investigated the effects of pharmacological AKT and MAPK pathway inhibitors on chemosensitivity of melanoma cells to cisplatin and temozolomide. Chemosensitivity was tested by examining effects on growth, cell cycle, survival, expression of antiapoptotic proteins, and invasive tumor growth of melanoma cells in monolayer and organotypic culture, respectively.

Eosinophilic globules in 3 cases of glomeruloid hemangioma of the head and neck: a characteristic offering more evidence for thanatosomes with or without POEMS.

Glomeruloid hemangiomas (GHs) are glomeruli-like capillary tufts lined by endothelial cells that contain periodic acid-Schiff (PAS) positive eosinophilic globules (EGs). These hemangiomas are characteristic cutaneous manifestation of POEMS syndrome (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, and Skin changes). Hemangiomas histologically identical to GHs but not associated with POEMS have recently been designated as papillary hemangiomas.

Amended reports: development and validation of a taxonomy of defects.

Amended pathology reports produce rework, confusion, and distrust. To develop a reproducible amendment taxonomy we derived a classification from 141 amended reports, then validated it with 130 new cases before 4 observers independently reviewed 430 cases measuring agreement (k). Next, agreement in classifying 30 other amended reports in 7 institutions was measured.

Revealing magnetic interactions from single-atom magnetization curves.

The miniaturization of magnetic devices toward the limit of single atoms calls for appropriate tools to study their magnetic properties. We demonstrate the ability to measure magnetization curves of individual magnetic atoms adsorbed on a nonmagnetic metallic substrate with use of a scanning tunneling microscope with a spin-polarized tip. We can map out low-energy magnetic interactions on the atomic scale as evidenced by the oscillating indirect exchange between a Co adatom and a nanowire on Pt(111).

Immunohistochemical staining of palisading basal cells in Bowen's disease and basal involvement in actinic keratosis: contrasting staining patterns suggest different cells of origin.

Actinic keratosis (AK) and Bowen's disease (BD) are common patterns of in situ squamous cell carcinoma of the epidermis. In AK, atypical keratinocytes proliferate in the lower portion of the epidermis including the basal layer. In contrast, BD features atypical squamous cells in all portions of the epidermis but initially leaves basal cells in palisades along the basement membrane.

Combined inhibition of MAPK and mTOR signaling inhibits growth, induces cell death, and abrogates invasive growth of melanoma cells.

The RAS-RAF-MEK-ERK and PI3K-AKT-mTOR signaling pathways are activated through multiple mechanisms and appear to play a major role in melanoma progression. Herein, we examined whether targeting the RAS-RAF-MEK-ERK pathway with the RAF inhibitor sorafenib and/or the PI3K-AKT-mTOR pathway with the mTOR inhibitor rapamycin has therapeutic effects against melanoma. A combination of sorafenib (4 microM) with rapamycin (10 nM) potentiated growth inhibition in all six metastatic melanoma cell lines tested.

Age and gender are significant independent predictors of survival in primary cutaneous melanoma.

Background: The aim was to identify age- related and gender-related differences in the clinical presentation and outcome of patients with primary cutaneous melanoma (CM).

Methods: A total of 4785 CM patients without clinical evidence of metastasis diagnosed during the period 1976-2001 in southern Germany included in the analysis. Kaplan-Meier analyses were performed to estimate and to compare disease-specific survival (DSS) and survival after first recurrence (SAR).

The influence of arthroscopic subscapularis tendon and capsule release on internal rotation strength in treatment of frozen shoulder.

Background: Arthroscopic release of the capsule is a popular treatment option for chronic refractory frozen shoulder. Additional release of the intra-articular part of the subscapularis is controversial regarding possible impairment of subscapularis function.

Hypothesis: Arthroscopic release of the intra-articular part of the subscapularis produces good clinical results and does not lead to reduced internal rotation strength.

Local electronic structure near Mn acceptors in InAs: surface-induced symmetry breaking and coupling to host states.

We present low-temperature scanning tunneling spectroscopy measurements on Mn acceptors in InAs in comparison with tight-binding calculations. We find a strong (001)-mirror asymmetry of the bound hole wave function close to the (110) surface. In addition, multiple acceptor-related peaks are observed and are attributed to a spin-orbit splitting of the acceptor level.

Frequency and outcome of cervical cancer prevention failures in the United States.

We measured the frequency and outcome of cervical cancer prevention failures that occurred in the Papanicolaou (Pap) and colposcopy testing phases involving 1,646,580 Pap tests in 4 American hospital systems between January 1, 1998, and December 31, 2004. We defined a screening failure as a 2-step or greater discordant Pap test result and follow-up biopsy diagnosis. A total of 5,278 failures were detected (0.

ProSAS: a database for analyzing alternative splicing in the context of protein structures.

Alternative splicing is known to be one of the major sources for functional diversity in higher eukaryotes. Several splicing isoforms have been characterized in the literature that play important roles in cellular processes like apoptosis or signal transduction pathways. Splicing events can often be detected on the mRNA level by large-scale cDNA or EST experiments and such data is collected and annotated in several databases.

A comprehensive chemoselective and enantioselective 2D-HPLC set-up for fast enantiomer analysis of a multicomponent mixture of derivatized amino acids.

A feasibility study on the fast enantioselective two-dimensional HPLC separation of racemic amino acid derivatives is presented. The method involves the on-line coupling of a narrow-bore C18 RP column in the first dimension to a short enantioselective column based on nonporous 1.5 microm particles modified with quinidine carbamate as chiral selector in the second dimension.

Factors related to medical appointment attendance after childbirth among HIV-infected women in the Paris region.

This study examined factors related to medical appointment attendance after childbirth among HIV-infected women in the Paris region. We hypothesized that despite regular utilization of prenatal care, many women may not attend medical appointments after delivery for their own HIV infection. This was an observational cohort study of HIV-seropositive women delivering in four Paris hospitals in 2001.

Clinical laboratory specimen rejection--association with the site of patient care and patients' characteristics: findings from a single health care organization.

Context: Programs to track laboratory quality have reported aggregated specimen rejection rates ranging from 0.30% to 0.83%.

Combined targeting of MAPK and AKT signalling pathways is a promising strategy for melanoma treatment.

Background: In melanoma, several signalling pathways are constitutively activated. Among them, the RAS/RAF/MEK/ERK (MAPK) and PI3K/AKT (AKT) signalling pathways are activated through multiple mechanisms and appear to play a major role in melanoma development and progression.

Objectives: In this study, we examined whether targeting the MAPK and/or AKT signalling pathways would have therapeutic effects against melanoma.

The increased expression of Y box-binding protein 1 in melanoma stimulates proliferation and tumor invasion, antagonizes apoptosis and enhances chemoresistance.

In previous studies we identified the transcription/translation factor Y-box-binding protein (YB-1) as a gene that is upregulated in primary melanoma and melanoma metastases when compared to benign melanocytic nevi. To analyze whether YB-1 expression correlates with melanoma progression in vitro and in vivo, we performed expression analysis on melanoma cell lines representing different stages of melanoma progression and on tissues of melanocytic nevi, primary melanoma and melanoma metastases. Our data indicate that compared to benign melanocytes YB-1 expression is increased in melanoma cells in vitro and in vivo and that YB-1 is translocated into the nucleus in invasive and metastatic melanoma cells.

Improvement of overall survival of patients with cutaneous melanoma in Germany, 1976-2001: which factors contributed?

Background: A hypothesis generated a retrospective analysis of the improvement of survival over time in patients with cutaneous melanoma (CM) in order to identify factors contributing to this progress.

Methods: A cohort of 4791 patients diagnosed with primary CM in southern Germany between 1976 and 2001 was analyzed. Kaplan-Meier analyses were performed to estimate and to compare overall survival (OS) and survival after first recurrence (SAR).