P2X3 is expressed by DRG neurons that terminate in inner lamina II

The P2X3 receptor subunit, a member of the P2X family of ATP-gated ion channels, is almost exclusively localized in sensory neurons. In the present study, we sought to gain insight into the role of P2X3 and P2X3-containing neurons in sensory transmission, using immunohistochemical approaches. In rat dorsal root ganglia (DRG), P2X3-immunoreactivity (-ir) was observed in small- and medium-sized neurons. Approximately 40% of DRG neuronal profiles in normal rats contained P2X3-ir. In rats that had received neonatal capsaicin treatment, the number of P2X3-positive neurons was decreased by approximately 70%. Analysis of the colocalization of P2X3-ir with cytochemical markers of DRG neurons indicated that approximately 94% of the P2X3-positive neuronal profiles were labelled by isolectin B4 from Bandeiraea simplicifolia, while only 3% contained substance P-ir, and 7% contained somatostatin-ir. In dorsal horn of rat spinal cord, P2X3-ir was observed in the inner portion of lamina II and was reduced subsequent to dorsal rhizotomy, as well as subsequent to neonatal capsaicin treatment. Finally, P2X3-ir accumulated proximal to the site of sciatic nerve ligation, and was seen in nerve fibres in skin and corneal epithelium. In summary, our results suggest that P2X3 is expressed by a functionally heterogeneous population of BSI-B4-binding sensory neurons, and is transported into both central and peripheral processes of these neurons.     

Hexafluorozirconic acid based surface pretreatments: Characterization and performance assessment

A new phosphate-free pretreatment from Henkel Corp. named TecTalis^®, was investigated. The treatment bath is composed of dilute hexafluorozirconic acid with small quantities of non-hazardous components containing Si and Cu. The corrosion resistance of treated steel was compared to samples treated in a phosphate conversion coating bath, in simple hexafluorozirconic acid and in TecTalis without the addition of the Cu-containing component. Atomic Force Microscopy (AFM) and Transmission Electron Microscopy (TEM) were used to characterize the coating surface morphology, structure and composition. A Quartz Crystal Microbalance (QCM) was used for studying film growth kinetics on thin films of pure Fe, Al and Zn. Electrochemical Impedance Spectroscopy (EIS) was performed on treated and painted steel for studying long-term corrosion performance of the coatings. The phosphate-free coating provided long-term corrosion performance comparable to that of phosphate conversion coatings. The coatings uniformly cover the surface in the form of 10–20 nm sized nodules and clusters of these features up to 500 nm in size. The coatings are usually about 20–30 nm thick and are mostly composed of Zr and O with enrichment of copper at randomly distributed locations and clusters.     

Effects of size and orientation change on hippocampal activation during episodic recognition: a PET study

To determine whether physical match between studied and tested items influences blood flow increases in the hippocampal formation associated with recognition memory, positron emission tomography (PET) was used to measure changes in regional cerebral blood flow while healthy volunteers made old/new judgements about line drawings of objects. Some objects were tested in the same size and orientation as they had appeared earlier during the study phase of the experiment; other objects were tested in a different size or orientation than when they were studied. Blood flow increases in the vicinity of the hippocampal formation were observed in the same object condition compared with the size change and the orientation change conditions, even though recognition accuracy was affected significantly only by orientation change. Results add to previous findings suggesting that physical similarity between studied items and test cues may contribute to hippocampal activation during episodic retrieval.     

On the transport of a suspended particle in flow through the entrance region of a tube

The motion of a single, spherical particle, released at different radial positions at the inlet of the entrance region of a straight circular laminar flow tube (Re = 260), was studied theoretically. Radial migration of the particle, either toward the tube center or toward the tube wall, was predicted. Based on the hypothesis that the particle experienced a lift force which was produced by the vorticity in the boundary layer and a velocity difference between the center of the suspended particle and the fluid medium, an inertia-vorticity fluid dynamic model was formulated to analyze the particle radial motions. Computational flow dynamics (CFD) solutions obtained from a 9.8 mm diameter tube model included the resulting particle loci for three particle radii (a = 0.1 cm, 0.085 cm, 0.050 cm), with the particle entry at various radial positions. The computation also covered a range of different particle entry speeds. The results showed that the particle migrates toward the tube center if it lags behind the medium in the core region; otherwise, it migrates toward the tube wall. Additional flow experiments were conducted in a circular (2R = 10.2 mm), 300 mm long straight tube. A small polystyrene sphere (2a = 1.72 mm, density rho p = 1.014 g.cm-3) was released at the inlet (X = 0, eta/R = 0.48) with two dimesionless release velocities (omega p = 0, and omega p > 1.0). The recorded particle traces agree well with the computational model.     

THERMAL STRESSES IN PARTIALLY ABSORBING FLAT PLATE DUE TO SUDDEN INTERRUPTION OF STEADY-STATE ASYMMETRIC RADIATION,I: CONVECTIVE COOLING AT REAR SURFACE

An analysis is presented of the thermal stresses in a partially absorbing flat plate due to sudden interruption of steady-state asymmetric thermal radiation on the front face with convection cooling at the rear face. Maximum transient tensile stresses occur in the rear surface and are almost independent of the heat transfer coefficient, h. For optical thicknesses of ≥ 0.5 μa, the maximum tensile stress initially rises to reach a peak and then decreases with time. In contrast, for thicknesses ≤ 0.5 μa, the stresses decrease monotonically. It is shown that a plot of nondimensional stress as a function of nondimensional time for a given value of pa and h does not result in a universal plot from which thermal stresses can be obtained for any value of plate thickness.     

Cloning, expression and sequence analysis of the SphI restriction-modification system

SphI, a type II restriction-modification (R-M) system from the bacterium Streptomyces phaeochromogenes, recognizes the sequence 5'-GCATGC. The SphI methyltransferase (MTase)-encoding gene, sphIM, was cloned into Escherichia coli using MTase selection to isolate the clone. However, none of these clones contained the restriction endonuclease (ENase) gene. Repeated attempts to clone the complete ENase gene along with sphIM in one step failed, presumably due to expression of SphI ENase gene, sphIR, in the presence of inadequate expression of sphIM. The complete sphIR was finally cloned using a two-step process. PCR was used to isolate the 3' end of sphIR from a library. The intact sphIR, reconstructed under control of an inducible promoter, was introduced into an E. coli strain containing a plasmid with the NlaIII MTase-encoding gene (nlaIIIM). The nucleotide sequence of the SphI system was determined, analyzed and compared to previously sequenced R-M systems. The sequence was also examined for features which would help explain why sphIR unlike other actinomycete ENase genes seemed to be expressed in E. coli.     

A phase I study of recombinant human soluble interleukin-1 receptor (rhu IL-1R) in patients with relapsed and refractory acute myeloid leukemia

PURPOSE: The recombinant human interleukin-1 receptor (rhu IL-1R) is a soluble truncated form of the type 1 full-length membrane-bound receptor that binds IL-1 with identical affinity to that of the membrane form. As such, it may have clinical potential by sequestering IL-1, thereby preventing it from binding to its membrane-bound receptor and eliciting a biological effect. As IL-1 has been shown to regulate leukemic cell proliferation in an autocrine fashion, a phase I trial of rhu IL-1R was conducted in patients with relapsed and refractory acute myeloid leukemia (AML). METHODS: The study group comprised 11 patients who were sequentially treated on one of three dose levels, receiving a single intravenous (i.v.) bolus dose on day 1 followed by 13 days of daily subcutaneous (s.c.) injections with the option of an additional 14 days of treatment if a response of stable disease or better was achieved. Dose level 1 i.v. bolus 500 microg/m2, s.c. dose 250 microg/m2 per day (five patients); dose level 2 i.v. bolus 1000 microg/m2, s.c. dose 500 microg/m2 per day (three patients); dose level 3 i.v. bolus 2000 microg/m2, s.c. dose 1000 microg/m2 per day (three patients). Owing to limited drug availability, the study was designed to only examine these three dose levels. RESULTS: rhu IL-IR was well tolerated. There was no grade 3 or 4 non-hematological toxicity related to the study drug and the maximum tolerated dose was not reached. No IL-1R-blocking antibodies developed during the course of the study. Serum levels of IL-1beta, IL-6 and TNF were undetectable before, during and after rhu IL-IR administration. The terminal half-life after i.v. dosing was at least 7-12 h, and after s.c. dosing 2-4 days. Serum levels of rhu IL-1R up to 360- and 25-fold those of pretreatment levels were achieved after i.v. and s.c. dosing respectively. No patient had a complete, partial or minor response to treatment; four had stable disease and seven had progressive disease. CONCLUSIONS: rhu IL-1R therapy was safe but did not have any apparent antileukemic effect at the doses administered.