Exploring Renner-Teller induced quenching in the reaction H(2S)+NH(a 1Delta): a combined experimental and theoretical study.

Experimental rate coefficients for the removal of NH(a (1)Delta) and ND(a (1)Delta) in collisions with H and D atoms are presented; all four isotope combinations are considered: NH+H, NH+D, ND+H, and ND+D. The experiments were performed in a quasistatic laser-flash photolysis/laser-induced fluorescence system at low pressures. NH(a (1)Delta) and ND(a (1)Delta) were generated by photolysis of HN(3) and DN(3), respectively.

Molecular correlates of gefitinib responsiveness in human bladder cancer cells.

We characterized the effects of the small molecule epidermal growth factor receptor (EGFR) inhibitor gefitinib (ZD1839, Iressa) on cell proliferation in a panel of 17 human bladder cancer cell lines. Gefitinib inhibited DNA synthesis in a concentration-dependent fashion in 6 of 17 lines. Growth inhibition was associated with p27(Kip1) accumulation and decreased cyclin-dependent kinase 2 activity.

Loss of AP-2alpha results in deregulation of E-cadherin and MMP-9 and an increase in tumorigenicity of colon cancer cells in vivo.

Activator protein-2 (AP-2) is a transcription factor that regulates proliferation and differentiation in mammalian cells and has been implicated in the acquisition of the metastatic phenotype in several types of cancer. Herein, we examine the role of AP-2alpha in colon cancer progression. We provide evidence for the lack of AP-2alpha expression in the late stages of colon cancer cells.

Endoscopic argon plasma coagulation of Marlex mesh erosion after vertical-banded gastroplasty.

Background: Marlex mesh erosions may occur as late complications after vertical-banded gastroplasty. Experience with the endoscopic treatment is limited.

Objective: To describe the use of argon plasma coagulation in the endoscopic treatment of eroded Marlex mesh.

Osseous stress reaction in a rower diagnosed with positron emission tomography (PET): a case report.

Back injury is one of the most frequently encountered injuries in the collegiate rower. The differential diagnosis of back pain in the competitive rower includes muscle strain, ligament/tendon injury, stress reaction, stress fracture, and a tear in the annulus fibrosis. Endurance sports, such as rowing, have an increased frequency of stress injury The diagnosis of stress reaction cannot be made with plain radiographs.

Mutations within the kinase domain and truncations of the epidermal growth factor receptor are rare events in bladder cancer: implications for therapy.

Purpose: It has previously been reported that the patient response to gefitinib depends on the presence of mutations within the kinase domain of epidermal growth factor receptor (EGFR) or the expression of its truncated form, EGFR variant III (EGFRvIII). The focus of this study was to determine if these alterations are present within the tyrosine kinase and ligand-binding domain of EGFR in urothelial carcinoma.

Experimental Design: The kinase domain found within exons 18 to 21 of the EGFR from 11 bladder cancer cell lines and 75 patient tumors were subjected to automated sequencing.

NMR structure of a potent small molecule inhibitor bound to human keratinocyte fatty acid-binding protein.

The NMR structure is presented for compound 1 (BMS-480404) (Ki = 33 (+/-2) nM) bound to keratinocyte fatty acid-binding protein. This article describes interactions between a high affinity drug-like compound and a member of the fatty acid-binding protein family. A benzyl group ortho to the mandelic acid in 1 occupies an area of the protein that fatty acids do not normally contact.

Schedule dependent efficacy of gefitinib and docetaxel for bladder cancer.

Purpose: We determined the sequence specific efficacy of gefitinib and docetaxel treatment for bladder cancer. This combination was selected because it is currently under study in a phase II clinical trial.

Materials And Methods: In vitro antiproliferative effects of gefitinib, docetaxel and a combination were determined in the 4 bladder cancer cell lines 253J B-V, UM-UC-3, KU-7 and UM-UC-13 by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay.

Difficult-to-engage patients: a specific target for time-limited assertive outreach in a Swiss setting.

Objective: Assertive community treatment (ACT) failed to develop in Europe, and its efficacy is debated. In Lausanne, Switzerland, ACT focuses on difficult-to-engage patients and aims to facilitate linkage with outpatient care through time-limited interventions. This study aimed to evaluate the applicability and efficiency of time-limited ACT.

Influence of the distillation step on the ratios of stable isotopes of ethanol in cherry brandies.

Isotope ratio mass spectrometry and site-specific natural isotope fractionation-nuclear magnetic resonance were applied to determine the overall carbon isotope ratio (delta13C) and the hydrogen isotope ratios [(D/H)I and (D/H)II] of ethanol, respectively. Ethanol was obtained by distillation of fermented cherry mash from a pot still commonly used in fruit brandy production. Analyses of distillate fractions revealed that the distillation proceeds with a fractionation of ethanol isotopologues.

Phosphorylated l-caldesmon is involved in disassembly of actin stress fibers and postmitotic spreading.

The function of the ubiquitous actin-binding protein, caldesmon (l-CaD) in mammalian non-muscle cells remains elusive. During mitosis, l-CaD becomes markedly phosphorylated at Ser497 and Ser527 (in the rat sequence), therefore, it has been suggested that l-CaD is involved in cytokinesis by inhibiting the actomyosin interaction until it is phosphorylated, although direct in vivo evidence is still missing. In the present study, we used F-actin staining and specific antibodies against these two phosphorylation sites of l-CaD to simultaneously monitor actin assembly and l-CaD phosphorylation.

Uncoupling between epidermal growth factor receptor and downstream signals defines resistance to the antiproliferative effect of Gefitinib in bladder cancer cells.

Activation of the epidermal growth factor receptor (EGFR) and downstream signaling pathways, such as phosphatidylinositol-3 kinase/Akt and Ras/mitogen-activated protein kinase (MAPK), have been implicated in causing resistance to EGFR-targeted therapy in solid tumors, including the urogenital tumors. To investigate the mechanism of resistance to EGFR inhibition in bladder cancer, we compared EGFR tyrosine kinase inhibitor (Gefitinib, Iressa, ZD1839) with respect to its inhibitory effects on three kinases situated downstream of EGFR: MAPK, Akt, and glycogen synthase kinase-3beta (GSK-3beta). We found that the resistance to the antiproliferative effects of gefitinib, in vitro as well as in vivo in nude mice models, was associated with uncoupling between EGFR and MAPK inhibition, and that GSK-3beta activation and degradation of its target cyclin D1 were indicators of a high cell sensitivity to gefitinib.

Multimers of the fibroblast growth factor (FGF)-FGF receptor-saccharide complex are formed on long oligomers of heparin.

The minimal signalling unit for tyrosine kinase receptors is two protomers dimerized by one or more ligands. However, it is clear that maximal signalling requires the formation of larger complexes of many receptors at discrete foci on the cell surface. The biological interactions that lead to this are likely to be diverse and have system specific components.

Experimental and theoretical investigations of the reactions NH(X 3Sigma-) + D(2S)-->ND(X 3Sigma-) + H(2S) and NH(X 3Sigma-) + D(2S)-->N(4S) + HD(X 1Sigmag+).

The rate coefficient of the reaction NH(X (3)Sigma(-))+D((2)S)-->(k(1) )products (1) is determined in a quasistatic laser-flash photolysis, laser-induced fluorescence system at low pressures. The NH(X) radicals are produced by quenching of NH(a (1)Delta) (obtained in the photolysis of HN(3)) with Xe and the D atoms are generated in a D(2)/He microwave discharge. The NH(X) concentration profile is measured in the presence of a large excess of D atoms.

Clinical applications for targeted therapy in bladder cancer.

The tremendous amount of data accumulated through genomics, proteomics, and metabolomic technologies has not led to a definitive understanding of the mechanisms underlying cancer. The challenge remains as to how to integrate all of the relevant knowledge and data in a systematic manner so that researchers can gain the knowledge needed to devise the best therapeutic and diagnostic strategies. Human transitional cell carcinoma of the bladder is genetically heterogeneous, and it is surrounded by a complex tissue microenvironment involving vasculature, stromal cells, and connective tissue.

Experimental and theoretical investigation of the reaction NH(X3Sigma-) + H(2S)-->N(4S) + H2(X1)Sigmag +).

The rate coefficient of the reaction NH(X (3)Sigma(-)) + H((2)S)-->(k(1a) )N((4)S) + H(2)(X (1)Sigma(g) (+)) is determined in a quasistatic laser-flash photolysis, laser-induced fluorescence system at low pressures (2 mbar< or =p< or =10 mbar). The NH(X) radicals are produced via the quenching of NH(a(1)Delta) (obtained by photolyzing HN(3)) with Xe whereas the H atoms are generated in a H(2)He microwave discharge. The NH(X) concentration profile is measured under pseudo-first-order condition, i.

Subcellular distribution of GABA(B) receptor homo- and hetero-dimers.

GBRs (GABA(B) receptors; where GABA stands for gamma-aminobutyric acid) are G-protein-coupled receptors that mediate slow synaptic inhibition in the brain and spinal cord. In vitro assays have previously demonstrated that these receptors are heterodimers assembled from two homologous subunits, GBR1 and GBR2, neither of which is capable of producing functional GBR on their own. We have used co-immunoprecipitation in combination with bioluminescence and fluorescence resonance energy transfer approaches in living cells to assess directly the interaction between GBR subunits and determine their subcellular localization.

Intravesical Ad-IFNalpha causes marked regression of human bladder cancer growing orthotopically in nude mice and overcomes resistance to IFN-alpha protein.

We have produced prolonged, high local concentrations of interferon in vivo by intravesical instillation of adenoviruses encoding interferon-alpha (Ad-IFNalpha) together with the gene transfer-enhancing agent Syn3. We found sustained interferon protein levels for days, both in normal mouse urothelium and in human bladder cancer cells growing as superficial bladder tumors in nude mice using an orthotopic bladder model developed by us. Tumor burden in the bladder was determined utilizing cancer cells containing the green fluorescent protein.

Optimization of a fully 3D single scatter simulation algorithm for 3D PET.

We describe a new implementation of a single scatter simulation (SSS) algorithm for the prediction and correction of scatter in 3D PET. In this implementation, out of field of view (FoV) scatter and activity, side shields and oblique tilts are explicitly modelled. Comparison of SSS predictions with Monte Carlo simulations and experimental data from uniform, line and cold-bar phantoms showed that the code is accurate for uniform as well as asymmetric objects and can model different energy resolution crystals and low level discriminator (LLD) settings.

[High resolution reconstruction of PET images using the iterative OSEM algorithm].

Aim: Improvement of the spatial resolution in positron emission tomography (PET) by incorporation of the image-forming characteristics of the scanner into the process of iterative image reconstruction.

Methods: All measurements were performed at the whole-body PET system ECAT EXACT HR(+) in 3D mode. The acquired 3D sinograms were sorted into 2D sinograms by means of the Fourier rebinning (FORE) algorithm, which allows the usage of 2D algorithms for image reconstruction.

Quinolines as extremely potent and selective PDE5 inhibitors as potential agents for treatment of erectile dysfunction.

In a continuing effort to discover novel chemotypes as potent and selective PDE5 inhibitors for the treatment of male erectile dysfunction (ED), we have found that 4-benzylaminoquinoline derivatives are very potent and selective PDE5 inhibitors. Some compounds in this series had PDE5 IC(50)'s as low as 50 pM. While an electron withdrawing group at the C6-position of the quinoline substantially improved PDE5 potency, an ethyl group at the C8-position not only improved the PDE5 potency but also the isozyme selectivity.

The epidermal growth factor receptor tyrosine kinase inhibitor ZD1839 (Iressa) suppresses c-Src and Pak1 pathways and invasiveness of human cancer cells.

Purpose: Abnormalities in the expression and signaling pathways downstream of the epidermal growth factor receptor (EGFR) contribute to the progression, invasion, and maintenance of the malignant phenotype in human cancers, including those of the head and neck and breast. Accordingly, agents such as the EGFR tyrosine kinase inhibitor (EGFR-TKI) ZD1839 (Iressa) are promising, biologically based treatments that are in various stages of preclinical and clinical development. The process of tumor progression requires, among other steps, increased transformation, directional migration, and enhanced cell survival; this study explored the effect of ZD1839 on the stimulation of c-Src and p21-activated kinase 1 (Pak1), which are vital for transformation, directional motility, and cell survival of cancer cells.

Use of ECT in idiopathic intracranial hypertension.

In 2001 the Second Edition of the American Psychiatric Association's Task Force Report on ECT maintained that no absolute contraindications to ECT exist. They warned, however, that ECT in persons with elevated intracranial pressure should be considered on a case-by-case risk to benefit ratio. Literature on the use of ECT in patients with elevated intracranial pressures is limited to space-occupying lesions as a cause for elevated pressures.

Performance of a brain PET camera based on anger-logic gadolinium oxyorthosilicate detectors.

Unlabelled: A high-sensitivity, high-resolution brain PET scanner ("G-PET") has been developed. This scanner is similar in geometry to a previous brain scanner developed at the University of Pennsylvania, the HEAD Penn-PET, but the detector technology and electronics have been improved to achieve enhanced performance.

Methods: This scanner has a detector ring diameter of 42.