Measurement of the kinetics of biomolecular interactions using the IAsys resonant mirror biosensor.

In this unit, the resonant mirror biosensor or IAsys, produced by Affinity Sensors, is discussed for the measurement of the kinetics of biomolecular interactions. All biosensors operate using a common principle--that binding events occurring on the sensing surface of the biosensor are converted by a transducer into an electronic signal which can then be processed by a computer to yield information on the amount of binding. Where biosensors vary is in their configuration and the nature of the transducer.

A novel mechanism for TNF-alpha regulation by p38 MAPK: involvement of NF-kappa B with implications for therapy in rheumatoid arthritis.

TNF-alpha is a key factor in a variety of inflammatory diseases. This study examines the role of p38 MAPK in the regulation of TNF-alpha in primary human cells relevant to inflammation, e.g.

Initial observations on the effect of irradiation on the liver-specific uptake of Levovist.

The aim of this pilot study was to see if the biodistribution of the microbubble Levovist (SHU 508 A; Schering AG, Berlin) during its liver specific phase is altered by radiotherapy. The mechanism of this liver-specific phase of this agent remains poorly understood. One way of investigating this is to see what effect radiotherapy has on liver uptake, as both Kupffer cell function and vascular endothelial integrity are selectively damaged by irradiation.

Transcription factor dosage affects changes in higher order chromatin structure associated with activation of a heterochromatic gene.

The mechanisms of transcriptional activation in heterochromatin were investigated by using FISH to directly visualize changes in chromatin organization during activation of a heterochromatic lambda5 transgene. A DNase I hypersensitive site was shown to relocate the transgene to the outside of the pericentromeric heterochromatin complex in the absence of transcription. Activation of transcription, which is dependent on the transcription factor EBF, occurs in a stochastic manner that resembles telomeric silencing in yeast, with the transcribed gene remaining closely associated with the heterochromatin complex.

Magnetic resonance imaging of the primary site in stage I cervical carcinoma: A comparison of endovaginal coil with external phased array coil techniques at 0.5T.

Objective: To compare endovaginal with pelvic phased array coil magnetic resonance imaging (MRI) in detection of Stage I cervical carcinoma by correlating the findings with histopathology.

Patients And Methods: Forty consecutive patients with Stage I cervical carcinoma confirmed histologically were studied using an endovaginal coil alone immediately followed by a pelvic phased array coil. T1-W transverse and T2-W FSE sagittal images made with each coil were analyzed independently by two radiologists noting the presence and size of a mass within the cervix and any parametrial extension or involvement of adjacent organs.

Goodness-of-fit statistics for age-specific reference intervals.

The age-specific reference interval is a commonly used screening tool in medicine. It involves estimation of extreme quantile curves (such as the 5th and 95th centiles) of a reference distribution of clinically normal individuals. It is crucial that models used to estimate such intervals fit the data extremely well.

Fusion of H4/D10S170 to the platelet-derived growth factor receptor beta in BCR-ABL-negative myeloproliferative disorders with a t(5;10)(q33;q21).

We have studied a patient who presented with clinical features suggestive of chronic myeloid leukemia in accelerated phase. BCR-ABL transcripts were undetectable by reverse transcription-PCR, but a novel reciprocal translocation, t(5;10)(q33;q21.2), was seen by standard cytogenetic analysis.

A useful monotonic non-linear model with applications in medicine and epidemiology.

In medicine and epidemiology monotonic curves are important as models for relations which prior knowledge or scientific reasoning dictate should increase or decrease consistently with the predictor value. An example is the monotonically increasing relation between cigarette consumption and the risk of coronary heart disease. In this paper I propose a new class of monotonic non-linear models which generalizes the well-known power and exponential transformations of a covariate.

A strategy for modelling the effect of a continuous covariate in medicine and epidemiology.

Low-dimensional parametric models are well understood, straightforward to communicate to other workers, have very smooth curves and may easily be checked for consistency with background scientific knowledge or understanding. They should therefore be ideal tools with which to represent smooth relationships between a continuous predictor and an outcome variable in medicine and epidemiology. Unfortunately, a seriously restricted set of such models is used routinely in practical data analysis - typically, linear, quadratic or occasionally cubic polynomials, or sometimes a power or logarithmic transformation of a covariate.

Choice of scale for cubic smoothing spline models in medical applications.

The determination of the functional form of the relationship between an outcome variable and one or more continuous covariates is an important aspect of the modelling of medical data. For correct interpretation of the data it is essential that the functional form be specified at least approximately correctly. I show that for given model complexity, logarithmic transformation of a covariate can greatly improve the fit of one of the most useful and convenient non-parametric regression models, the cubic smoothing spline.

Bile acids are physiological ligands for a nuclear receptor.

Bile acids are essential for the solubilization and transport of dietary lipids and are the major products of cholesterol catabolism. Results presented here show that bile acids are physiological ligands for the farnesoid X receptor (FXR), an orphan nuclear receptor. When bound to bile acids, FXR repressed transcription of the gene encoding cholesterol 7 alpha-hydroxylase, which is the rate-limiting enzyme in bile acid synthesis, and activated the gene encoding intestinal bile acid-binding protein, which is a candidate bile acid transporter.

Elevation of FVIII: C in venous thromboembolism is persistent and independent of the acute phase response.

Recent literature has suggested a role for elevated FVIII:C in venous thromboembolic disease (VTED). However since FVIII:C is known to rise in response to an acute phase reaction, it is difficult to determine whether the increased FVIII:C precedes the thrombosis or represents a secondary reactive phenomenon. In an attempt to address this question, we followed 35 patients with confirmed VTED, raised FVIII:C level (>1.

Potentiation of myoblast transplantation by host muscle irradiation is dependent on the rate of radiation delivery.

Transplantation of muscle precursor cells (mpc) has been suggested as a treatment for myopathies, such as Duchenne muscular dystrophy. Irradiation of skeletal muscle with 16-20 Gy prevents muscle regeneration and also augments muscle formation from implanted muscle precursor cells (mpc). However, when mdx nu/nu mouse muscles are preirradiated at 0.

SH2-Balpha is an insulin-receptor adapter protein and substrate that interacts with the activation loop of the insulin-receptor kinase.

We identified SH2-Balpha as an insulin-receptor-binding protein based on interaction screening in yeast hybrid systems and co-precipitation in cells. SH2-Balpha contains pleckstrin-homology ('PH') and Src homology 2 (SH2) domains and is closely related to APS (adapter protein with a PH domain and an SH2 domain) and lnk, adapter proteins first identified in lymphocytes. SH2-Balpha is ubiquitously expressed and is present in rat epididymal adipose tissue, liver and skeletal muscle, physiological sites of insulin action.

Respiratory syncytial virus-induced RANTES production from human bronchial epithelial cells is dependent on nuclear factor-kappa B nuclear binding and is inhibited by adenovirus-mediated expression of inhibitor of kappa B alpha.

Respiratory syncytial virus (RSV) infection is an important cause of lower respiratory tract illness, the severity of which may be partly due to cellular recruitment. RSV infection activates chemokine secretion from airway epithelial cells by largely unknown mechanisms. We investigated the regulation of RSV-induced activation of the chemokine RANTES in the bronchial epithelial cell line BEAS-2B and primary normal human tracheobronchial epithelial cultures.