Haemophilia A: mutation type determines risk of inhibitor formation

The formation of factor VIII antibodies is a major problem for replacement therapy of haemophilia A patients. Antibodies occur in 5-30% of patients with severe haemophilia A. The reason for antibody formation is still unknown. In this study we correlate for the first time different factor VIII gene mutations, stop- and missense mutations, large and small deletions and intrachromosomal intron 22 recombinations to antibody formation. A total of 364 patients with known inhibitor status of our institute, of the database, and of 3 studies representing intron-22-inversion data are included. The results show that the risk for developing factor VIII antibodies is strongly related to stop mutations. large deletions and intrachromosomal recombinations. A probable explanation could be the complete lack of endogenous circulating factor VIII protein in these cases. Other factors that might be important for the pathogenesis of inhibitor formation, e. g. the antenatal period, as well as possible therapeutic effects, are discussed.     

MR monitoring of focused ultrasonic surgery of renal cortex: experimental and simulation studies

The aim of the study was to test the hypothesis that magnetic resonance (MR) imaging-guided and -monitored noninvasive ultrasonic surgery can be performed in highly perfused tissues from outside the body. A simulation study was performed to evaluate the optimal sonication parameters. An MR-compatible positioning device was then used to manipulate a focused ultrasound transducer in an MR imager, which was used to sonicate kidneys of five rabbits at various power levels and different durations. Temperature elevation during sonication was monitored with a T1-weighted spoiled gradient-echo sequence. The simulation study demonstrated that a sharply focused transducer and relatively short sonication times (30 seconds or less) are necessary to prevent damage to the overlying skin and muscle tissue, which have a much lower blood perfusion rate than kidney. The experiments showed that the imaging sequence was sensitive enough to show temperature elevation during sonication, thereby indicating the location of the beam focus. Histologic evaluations showed that kidney necrosis could be consistently induced without damage to overlying skin and muscle. The study demonstrated that highly perfused tissues such as the renal cortex can be coagulated from outside the body with focused ultrasound and that MR imaging can be used to guide and monitor this surgery.     

High-reliability GaAs-AlGaAs HBTs by MBE with Be base doping andInGaAs emitter contacts

The authors have developed a modified MBE growth process to produce high-gain n-p-n GaAs-AlGaAs heterojunction bipolar transistors (HBTs) with a mean time to failure (MTTF) of 1.5×10⁸ h at 125°C. Beryllium incorporation and diffusion are controlled through a combination of reduced substrate temperature and increased As/Ga flux ratio during MBE growth, resulting in extremely stable HBT profiles. The authors also demonstrate graded InGaAs surface layers with nonalloyed refractory metal contacts that significantly improve ohmic reliability compared to alloyed AuGe contacts. The ability to produce robust HBTs by MBE is critically important to this technology     

Highly purified omega-3-polyunsaturated fatty acids for topical treatment of psoriasis. Results of a double-blind, placebo-controlled multicentre study

We report the results of a multicentre, double-blind, placebo-controlled study of topical therapy with omega-3-polyunsaturated fatty acids (omega-3-PUFA) in 52 patients suffering from moderate plaque-type psoriasis. In each patient, two similar stable psoriatic plaques served as indicator lesions for the study. One indicator lesion was randomly assigned to treatment with topical preparations of highly purified omega-3-PUFA in one of two concentrations (1 or 10%), and the other was treated with placebo. Efficacy assessment was based on changes in local psoriasis severity index, area involved, erythema, desquamation, induration and pruritus. After 8 weeks of treatment, all indicator lesions had improved significantly, compared with baseline. However, no statistically or clinically relevant differences between the omega-3-PUFA-treated and the placebo-treated lesions were found. Therapy was well tolerated and, apart from one patient who developed perilesional eczema, no clinically relevant adverse events occurred. In conclusion, topical omega-3-PUFA were not effective in a randomized, placebo-controlled, double-blind setting. Results of non-blind trials should be (re-)considered with caution.     

Fluorescence in situ hybridization mapping of the cystic fibrosis transmembrane conductance regulator (CFTR) gene to 7q31.3

We have used the fluorescence in situ hybridization (FISH) technique to refine the localization of the cystic fibrosis transmembrane conductance regulator (CFTR) gene on human chromosome 7. The result shows that the gene is most likely located within band q31.3.     

The side chains responsible for the dimerization of the estradiol receptor by ionic bonds are lost in a 17 kDa fragment extending downstream from aa 303

Fragments of 32, 26 and 17 kDa of the porcine estradiol receptor were prepared, all of which contain the ligand-binding site. While dimers of the 32 and 26 kDa fragments like those of intact receptor can be dissociated by protonation, the dimer of the 17 kDa fragment obtained by trypsination of the 26 kDa fragment is resistant to lowering the pH from 7.0 to 6.5 and below. Its dissociation can be achieved by 0.5 M MgCl2 at pH 7.0. All fragments are recognized by the MAB 13H2 in Western blots. The antibody also reacts with native receptor and the three fragments, both in their monomer and dimer states. The combining ratios of antibody with receptor, or its fragments, in the monomer and dimer states and the weakening of the estradiol-receptor bond by antibody attachment support the back to back and head to toe model of receptor dimers.     

Surface tailoring of an ethylene propylene diene elastomeric terpolymer via plasma‐polymerized coating of tetramethyldisiloxane

In the research presented here, we explore the use of a low‐energy plasma to deposit thin silicone polymer films using tetramethyldisiloxane (TMDSO) (H(CH₃)₂? Si? O? Si? (CH₃)₂H) on the surface of an ethylene propylene diene elastomeric terpolymer (EPDM) in order to enhance the surface hydrophobicity, lower the surface energy and improve the degradation/wear characteristics. The processing conditions were varied over a wide range of treatment times and discharge powers to control the physical characteristics, thickness, morphology and chemical structure of the plasma polymer films. Scanning electron microscopy (SEM) shows that pore‐free homogeneous plasma polymer thin films of granular microstructure composed of small grains are formed and that the morphology of the granular structure depends on the plasma processing conditions, such as plasma power and time of deposition. The thicknesses of the coatings were determined using SEM, which confirmed that the thicknesses of the deposited plasma‐polymer films could be precisely controlled by the plasma parameters. The kinetics of plasma‐polymer film deposition were also evaluated. Contact angle measurements of different solvent droplets on the coatings were used to calculate the surface energies of the coatings. These coatings appeared to be hydrophobic and had low surface energies. X‐ray photoelectron spectroscopy (XPS) and photoacoustic Fourier‐transform infrared (PA‐FT‐IR) spectroscopy were used to investigate the detailed chemical structures of the deposited films. The optimum plasma processing conditions to achieve the desired thin plasma polymer coatings are discussed in the light of the chemistry that takes place at the interfaces. Copyright © 2004 Society of Chemical Industry     

Towards a Dual-Tip STM Application in Mesoscopic Electron Transport

A new design for a dual-tip scanning tunneling microscope (STM) is presented. The design is a variation on the mechanically controllable break-junction with two electron beam-induced deposition nano-tips. The new design enables one to scan surfaces simultaneously with two probes having a nano-gap separation. By collecting the lateral current flowing between the tips, the transconductance map can then be compared with the STM images for local characterizations of the electron transport. Since the lateral beam carries the property of the density of states of the surface at momentum space, the dispersion of the electronic structure should give an orientation and position dependence of the local transconductance current. In addition, the reduced terminal separation, on the order of the characteristic mesoscopic length scales, is likely to be sensitive to a variety of typically observed interactions and interference effects.