BAY 43-9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis.

The RAS/RAF signaling pathway is an important mediator of tumor cell proliferation and angiogenesis. The novel bi-aryl urea BAY 43-9006 is a potent inhibitor of Raf-1, a member of the RAF/MEK/ERK signaling pathway. Additional characterization showed that BAY 43-9006 suppresses both wild-type and V599E mutant BRAF activity in vitro.

Challenges in treating obsessive-compulsive disorder: introduction.

This issue of In Session is devoted to challenges in the treatment of obsessive-compulsive disorder (OCD). The remarkable diversity of symptoms and the comorbidity in OCD pose substantial challenges to practitioners seeking to treat this disorder. After briefly reviewing the clinical features of OCD and its typical treatment, we provide brief descriptions of the six articles this issue comprises.

Essential role of BCL9-2 in the switch between beta-catenin's adhesive and transcriptional functions.

beta-Catenin controls both cadherin-mediated cell adhesion and activation of Wnt target genes. We demonstrate here that the beta-catenin-binding protein BCL9-2, a homolog of the human proto-oncogene product BCL9, induces epithelial-mesenchymal transitions of nontransformed cells and increases beta-catenin-dependent transcription. RNA interference of BCL9-2 in carcinoma cells induces an epithelial phenotype and translocates beta-catenin from the nucleus to the cell membrane.

Investigation of residues in the fibrin(ogen) gamma chain involved in tissue plasminogen activator binding and plasminogen activation.

In order to characterize tissue plasminogen activator (t-PA) binding to gamma-chain residues in fibrinogen, we generated variant fibrinogens substituting alanine for gamma D316, gamma D318, gamma D320, and gamma K321. We measured thrombin-catalyzed polymerization and found normal polymerization with gamma K321A, no polymerization with gamma D316A, and, as reported by Lounes et al. in 2002, impaired polymerization with gamma D318A and gamma D320A.

Ultra-high-throughput screening based on cell-surface display and fluorescence-activated cell sorting for the identification of novel biocatalysts.

Enzyme libraries displayed on the surface of microbial cells or microbeads can be screened with fluorogenic substrates that provide a physical linkage of the reaction product to the corresponding enzyme. Libraries exceeding 10(9) different variants can be quantitatively analysed and screened by flow cytometry at a rate of 30 000 cells/second. The promise of screening methods based on fluorescence-activated cell sorting for directed enzyme evolution is being realized and significantly improved enzymes have been reported recently.

[Zoonotic poxviruses].

In the last few years, the mass media and also scientists have been showing an increasing interest in poxviruses. What kind of infections can be found in animals and men today? The following review gives an overview on current taxonomy, properties, epidemiology, and diagnosis of zoonotic poxviruses.

A critical evaluation of obsessive-compulsive disorder subtypes: symptoms versus mechanisms.

Recently, experts have suggested that obsessive-compulsive disorder (OCD), a highly heterogeneous condition, is actually composed of distinct subtypes. Research to identify specific subtypes of OCD has focused primarily on symptom presentation. Subtype models have been proposed using factor analyses that yield dimensional systems of symptom categories, but not necessarily distinct subtypes.

No disgust recognition deficit in obsessive-compulsive disorder.

Background: Patients with basal ganglia abnormalities misclassify facial expressions of disgust as expressions of anger when asked to identify the emotion depicted in photographs of individuals displaying different emotions. Sprengelmeyer, Young, Pundt et al. (1997) reported a similar disgust recognition deficit in patients with obsessive-compulsive disorder (OCD)--an anxiety disorder associated with basal ganglia abnormality.

An algorithm to maximize use of minimally invasive parathyroidectomy.

Hypothesis: Minimally invasive parathyroidectomy (MIP) depends on accurate preoperative localization of abnormal parathyroid glands. If the findings of a technetium Tc 99m sestamibi-labeled single-photon emission computed tomography (SPECT) (hereafter referred to as sestamibi SPECT or scan) are negative or ambiguous, cervical ultrasonography (CUS) may increase the success of preoperative gland localization and MIP, avoiding bilateral neck exploration.

Design: We collected data regarding preoperative sestamibi SPECT and CUS for parathyroid gland localization and intraoperative findings.

Interpretive biases for ambiguous information in body dysmorphic disorder.

Anxiety-disordered patients and individuals with high trait anxiety tend to interpret ambiguous information as threatening. The purpose of this study was to investigate whether interpretive biases would also occur in body dysmorphic disorder (BDD), which is characterized by a preoccupation with imagined defects in one's appearance. We tested whether BDD participants, compared with obsessive-compulsive disorder participants and healthy controls, would choose threatening interpretations for ambiguous body-related, ambiguous social, and general scenarios.

Prospective clinical evaluation of a LightCycler-mediated polymerase chain reaction assay, a nested-PCR assay and a galactomannan enzyme-linked immunosorbent assay for detection of invasive aspergillosis in neutropenic cancer patients and haematological stem cell transplant recipients.

Invasive aspergillosis (IA) is a considerable clinical problem in neutropenic patients with haematological malignancies but its diagnosis remains difficult. We prospectively evaluated a LightCycler polymerase chain reaction (PCR) assay, a nested-PCR assay and a galactomannan (GM) enzyme-linked immunosorbent assay (ELISA) to validate their significance in diagnosing IA. During 205 treatment episodes in 165 patients from six centres, a nested-PCR assay and GM testing was performed at regular intervals.

Major depression due to primary hyperparathyroidism: a frequent and correctable disorder.

While primary hyperparathyroidism (primary HPT) is recognized as a correctable cause of nephrolithiasis and osteoporosis, its role as an organic cause of major depression is less clear. The rate of major depression in primary HPT, response of symptoms to parathyroidectomy, and potential cost benefits were reviewed. From August 1994 to September 2002, 360 patients underwent parathyroidectomy for primary HPT.

Treatment with campath-1H for relapsed chronic lymphocytic leukemia after allogeneic peripheral blood stem cell transplantation does not abrogate the development of chronic GVHD.

The graft vs. leukemia (GVL) effect is one of the most important factors of anti-tumor activity after allogeneic hematopoetic stem cell transplants (alloSCT). Its effectiveness depends mainly on the tumor biology as well as the tumor burden.

Emotion recognition deficits in body dysmorphic disorder.

Patients with Body Dysmorphic Disorder (BDD) are characterized by excessive concerns about imagined defects in their appearance, most commonly, facial features. In this study, we investigated (1) the ability to identify facial expressions of emotion, and (2) to discriminate single facial features in BDD patients, Obsessive-Compulsive Disorder (OCD) patients, and in healthy control participants. Specifically, their ability for general facial feature discrimination was assessed using the Short Form of the Benton Facial Recognition Test (Benton AL, Hamsher KdeS, Varney NR, Spreen O.

Bladder dysfunction and end stage renal disease.

Introduction And Objectives: Evaluation of lower urinary tract function in patients with end-stage renal disease and lower urinary tract symptoms. Patients were screened before entering a renal transplantation program.

Materials And Methods: A diagnostic work-up including urodynamics was performed on 52 patients (14 women, 38 men) suffering from renal failure due to chronic glomerulonephritis (n = 25), diabetic nephropathy (n = 15), chronic pyelonephritis/stone disease (n = 9) and polycystic kidney disease (n = 3).

Students' perspective of the effectiveness of an asynchronous on-line seminar.

This study was conducted to understand students' perceptions of the usefulness of on-line discussion for a nursing seminar. The interpretative approach was selected to explore the students' perceptions of the effectiveness of the on-line discussion. The participants were recruited from maternity nursing courses on two rural campuses in Nebraska.

Health-related quality of life in hyperparathyroidism measurably improves after parathyroidectomy.

Background: Hyperparathyroidism is associated with subjective feelings of fatigue and depression as well as limitations in physical activity from musculoskeletal complaints. These quality of life symptoms are not widely accepted as an indication for parathyroidectomy. This study quantifies and compares subjective symptoms of patients with hyperparathyroidism before and after surgery.

Reduced virulence of a hfq mutant of Pseudomonas aeruginosa O1.

The Sm-like protein Hfq has been implicated in the regulation of sigmaS-dependent and sigmaS-independent genes in E. coli and in the regulation of virulence factors in both, Yersinia enterocolitica and Brucella abortus. Here, we have studied the effect of Hfq on virulence and stress response of Pseudomonas aeruginosa (PAO1).

Sepsis in neutropenia--guidelines of the Infectious Diseases Working Party (AGIHO) of the German Society of Hematology and Oncology (DGHO).

Patients developing fever in neutropenia are at high risk of infection-related complications. Their outcome is influenced by the degree of severity (sepsis, severe sepsis and septic shock). Sepsis describes clinical syndromes resulting from systemic inflammatory response.

Treosulfan and fludarabine: a new toxicity-reduced conditioning regimen for allogeneic hematopoietic stem cell transplantation.

New conditioning regimens are being explored to reduce toxicity and enable allogeneic bone marrow transplantation in patients not eligible for conventional transplantation. We have investigated treosulfan, an alkylating agent, with the aim of developing an efficient and reliable but less-toxic conditioning regimen. A series of 30 patients who were not eligible for standard conditioning therapy received transplants from HLA-matched related (n = 14) or unrelated (n = 16) donors after administration of treosulfan 10 g/m2 intravenously daily for 3 days and fludarabine 30 mg/m2 intravenously daily for 5 days.

Negative priming for threatening vs. non-threatening information in body dysmorphic disorder.

Background: Individuals with body dysmorphic disorder (BDD) suffer from unpleasant, repetitive thoughts about imagined defects in appearance which are difficult to control.

Objective: The purpose of this study was to test for deficits in cognitive inhibition in BDD.

Methods: To test for deficits in cognitive inhibition in BDD, we applied a negative priming paradigm.