Transgenic models in renal tubular physiology

Animal transgenesis has proven to be useful for physiological as well as physiopathological studies. Besides the classical approach based on the random integration of a DNA construct in the mouse genome, gene targeting can be achieved using totipotent embryonic stem (ES) cells for targeted transgenesis. Transgenic mice are then derived from the transgenic ES cells. This allows the introduction of null mutations in the genome (so-called knock-out) or the control of the transgene expression by the endogenous regulatory sequences of the gene of interest (so-called knock-in). Development of these transgenic animals leads to a better understanding of the cellular function of many genes or to the generation of animal models for human diseases. The purpose of this short review is to describe animal models in renal tubular physiopathology. Recent progresses will allow the generation of animal models with conditional expression of the transgene of interest or with a conditional gene mutation. This permits spatial and temporal control of the expression of the transgene or of the mutation. This should allow the generation of models suitable for physiological analysis or closer to disease state.     

Demethylation of the progesterone receptor CpG island is not required for progesterone receptor gene expression

In a previous study we have shown that an intravenous infusion of pramlintide (an analogue of human amylin) delayed gastric emptying, but the dose of pramlintide was supraphysiological in relation to the amylin response to food in non-diabetic subjects. The purpose of this study was to examine the dose response relationship of subcutaneous injections of pramlintide on gastric emptying and to determine whether administration of the drug before one meal has an impact on the subsequent meal. Eleven men with insulin-dependent diabetes mellitus were studied in a double-blind, randomised, four-way crossover design. None had autonomic neuropathy. Euglycaemia was maintained overnight before the study day. At -30 min the patients self-injected their usual morning insulin and at -15 min they injected the study drug (either placebo or 30, 60 or 90 microg pramlintide) subcutaneously. At 0 min they ate a standard meal consisting of a pancake, labelled with 99mTc, and a milkshake containing 3-ortho-methylglucose (3-OMG). Gastric emptying images were obtained for the next 8 h. At 240 min the subjects ate a similar meal, but on this occasion the pancake was labelled with (111)In. All three doses of pramlintide delayed emptying of the solid component of the first meal (p < 0.004) with no significant difference between the drug doses. There were no differences between placebo and pramlintide after the second meal. All three doses of pramlintide resulted in a prolongation in the time to peak plasma 3-OMG level (p < 0.0001) after the first meal but there was no difference after the second meal.     

Beam-quality changes generated by thermally-induced sphericalaberration in laser cavities

Thermally-induced spherical aberration in Nd:YAG rods is investigated. Attention is concentrated on the so-called “intensity moment formalism” to analyze the beam-quality parameter of the emitted laser beams. A number of resonance conditions that certain beam-shape parameters of any stable laser mode should fulfill are also derived, and a comparison with previously reported numerical results is presented     

Systemic lupus erythematosus with a protein-losing enteropathy

Anasarca with pronounced hypoalbuminemia developed in a young woman 15 months after the onset of a mild, arthralgic type of systemic lupus erythematosus (SLE) without evidence of active nephritis. Investigation indicated a gastrointestinal rather than a renal site for protein loss. A full clinical remission was achieved with low-dose corticosteroid therapy.     

The use of microbial tracers to monitor seasonal variations in effluent retention in a constructed wetland

Effluent retention in a constructed wetland was determined using both microbial and chemical tracers. Seasonal variation in effluent retention was the main focus of the study. The biotracers used in the study were the coliphage MS2, a bacteriophage of Enterobacter cloacae and antibiotic resistant endospores of Bacillus globigii. Two separate tracer runs were conducted, Winter high flow (January 2002) and Summer low flow (June 2002). The three biotracers were evaluated simultaneously on both occasions, with the commonly used chemical tracer, rhodamine WT, a bright red fluorescent dye, being evaluated during the final experiment. The Winter tracer run was conducted during a typical Winter storm, with a mean effluent discharge of 4.1 ls(-1). Tracer recovery was 98% MS2, 91% Ent. cloacae phage and 2% endospore. Effluent retention was estimated at between 2 and 4 h at 90% phage tracer recovery. The Summer tracer run was conducted at a typical site operating discharge rate of 0.8 ls(-1). Tracer recovery was 23% MS2, 36% Ent. cloacae phage, 8% rhodamine and 14% for the endospores. Effluent retention was estimated at between 11 and 18 h at 90% of phage tracer recovery. Initial results are encouraging and indicate bacteriophage to have further potential as tracing agents in wetlands.     

Radionuclide biokinetics database (RBDATA-EULEP): an update

The main activity of the RBDATA-EULEP project is the development of an electronic database of information on the biokinetics of radionuclides after intake by inhalation, ingestion or injection. It consists of linked tables of publications and experiments, with details and comments on the materials, procedures and results. By March 2004 it contained information on more than 1600 experiments from 600 publications. It will be extended and Internet access will also be provided.     

Dosimetric models for thorium and practical problems in assessing intakes

An overview is given of the models recommended by the International Commission on Radiological Protection (ICRP) for assessing intakes and doses, and summarises biokinetic data obtained after the deposition of different chemical compounds of thorium in the rat lung. The results emphasise the importance of using material-specific data rather than default reference values for absorption into blood. The limitations of external monitoring of the chest or urine analysis are discussed, and comments made on alternative strategies for radiological protection of the worker.     

Stereolithographic models of biopolymers

Stereolithography (STL) has been used to make plastic models of the solvent accessible surfaces of biopolymers. Models have been made of proteins and proteins bound to DNA and RNA. The STL process uses a laser to photopolymerize a liquid resin. Using the ACES (accurate, clear, epoxy, solid) building technique, parts are made with minimum postcure shrinkage. Protein Data Bank files are converted to STL files that represent the surface topology of the biopolymer as a series of triangles and an index that describes their orientation. The models are useful in teaching biomolecular structure and the principle of docking. They are especially useful to the visually impaired.     

A first step towards a simple in-line shape compensation routine for the roll forming of high strength steel

The roll forming process is increasingly used in the automotive industry for the manufacture of structural and crash components from Ultra High Strength Steel (UHSS). Due to the high strength of UHSS (<1GPa) even small and commonly observed material property variations from coil to coil can result in significant changes in material yield and through that affect the final shape of the roll formed component. This requires the re-adjustment of tooling to compensate for shape defects and maintain part geometry resulting in costly downtimes of equipment. This paper presents a first step towards an in-line shape compensation method that based on the monitoring of roll load and torque allows for the estimation of shape defects and the subsequent re-adjustment of tooling for compensation. For this the effect of material property variation on common shape defects observed in the roll forming process as well as measurable process parameters such as roll load and torque needs to be understood. The effect of yield strength and material hardening on roll load and torque as well as longitudinal bow is investigated via experimental trials and numerical analysis. A regression analysis combined with Analysis of Variance (ANOVA) techniques is employed to establish the relationships between the process and material parameters and to determine their percentage influence on longitudinal bow, roll load and torque. The study will show that the level of longitudinal bow, one of the major shape defects observed in roll forming, can be estimated by variations in roll load and torque.