T-Cell receptor BV6S1 null alleles and HLA-DR1 haplotypes in polyarticular outcome juvenile rheumatoid arthritis

JRA is a complex of disease subtypes which are normally identified by clinical features such as age of onset and extent of joint involvement both at onset and during the course of the disease. We previously identified an association between TCR BV6S1 null allele and one subgroup of early-onset pauciarticular patients positive for HLA-DQA1*0101, an HLA haplotype predisposing to a polyarticular course of the disease. In this report we extend this observation by identifying an increased prevalence of this nonfunctional or null allele in the patients with a polyarticular disease course regardless of the mode of onset. This increase was most prominent in clinical subsets that have early onset of the disease and a polyarticular outcome. In one clinical group, stratification of patients by the HLA allele DQA1*0101 strengthened the association considerably. This implies that there is an increased genetic load defined by specific alleles of both MHC and TCR genes.     

The molecular structure of the DNA fragments eliminated during chromatin diminution in Cyclops kolensis

Presumptive somatic cells of the copepod Cyclops kolensis specifically eliminate a large fraction of their genome by the process of chromatin diminution. The eliminated DNA (eDNA) remains only in the germline cells. Very little is known about the nature of the sequences eliminated from somatic cells. We cloned a fraction of the eDNA and sequenced 90 clones that total 32 kb. The following organizational patterns were demonstrated for the eDNA sequences. All do not contain open reading frames. Each fragment contains 1-3 families of short repeats (10-30 bp) highly homologous within families (87%-100%). Most repeats are separated by spacers up to 50 bp long. Homologous regions were found between fragments, motifs from 15-300 bp in length. Among fragments there occur groups in which the same motifs are ordered in the same fashion. However, spacers between the motifs differ in length and nucleotide composition. Ubiquitous motifs (those occurring in all fragments) were identified. Analysis of motifs revealed submotifs, each occurring within several motifs. Thus, motifs may be regarded as mosaic structures composed of submotifs (short repeats). Taken together, the results provide evidence of a high organizational ordering of the DNA sequences restricted to the germline. With this in mind, it appears incorrect to refer to this part of the genome as junk. Moreover, eDNA is redundant for only the somatic cells-its function is to be sought in germline cells.     

Including robustness in multi-criteria optimization for intensity-modulated proton therapy

We present a method to include robustness in a multi-criteria optimization (MCO) framework for intensity-modulated proton therapy (IMPT). The approach allows one to simultaneously explore the trade-off between different objectives as well as the trade-off between robustness and nominal plan quality. In MCO, a database of plans each emphasizing different treatment planning objectives, is pre-computed to approximate the Pareto surface. An IMPT treatment plan that strikes the best balance between the different objectives can be selected by navigating on the Pareto surface. In our approach, robustness is integrated into MCO by adding robustified objectives and constraints to the MCO problem. Uncertainties (or errors) of the robust problem are modeled by pre-calculated dose-influence matrices for a nominal scenario and a number of pre-defined error scenarios (shifted patient positions, proton beam undershoot and overshoot). Objectives and constraints can be defined for the nominal scenario, thus characterizing nominal plan quality. A robustified objective represents the worst objective function value that can be realized for any of the error scenarios and thus provides a measure of plan robustness. The optimization method is based on a linear projection solver and is capable of handling large problem sizes resulting from a fine dose grid resolution, many scenarios, and a large number of proton pencil beams. A base-of-skull case is used to demonstrate the robust optimization method. It is demonstrated that the robust optimization method reduces the sensitivity of the treatment plan to setup and range errors to a degree that is not achieved by a safety margin approach. A chordoma case is analyzed in more detail to demonstrate the involved trade-offs between target underdose and brainstem sparing as well as robustness and nominal plan quality. The latter illustrates the advantage of MCO in the context of robust planning. For all cases examined, the robust optimization for each Pareto optimal plan takes less than 5 min on a standard computer, making a computationally friendly interface possible to the planner. In conclusion, the uncertainty pertinent to the IMPT procedure can be reduced during treatment planning by optimizing plans that emphasize different treatment objectives, including robustness, and then interactively seeking for a most-preferred one from the solution Pareto surface.     

A dose comparison study between XVI and OBI CBCT systems

The purpose of this study is to establish a comprehensive set of dose measurements data obtained from the X-ray Volumetric Imager (XVI, Elekta Oncology Systems) and the On-Board Imager (OBI, Varian Medical Systems) cone-beam CT (CBCT) systems. To this end, two uniform-density cylindrical acrylic phantoms with diameters of 18 cm (head phantom) and 30 cm (body phantom) were used for all measurements. Both phantoms included ion chamber placement holes in the center and at periphery (2 cm below surface). For the XVI unit, the four standard manufacturer-supplied protocols were measured. For the OBI unit, the full bow tie and half bow tie (and no bow tie) filters were used in combination with the two scanning modes; namely, full-fan and half-fan. The total milliampere x seconds (mA s) setting was also varied for each protocol to establish the linear relationship between the dose deposited and the mA s used (with all other factors being held constant). Half-value layers in aluminum (Al) were also measured for beam characteristic determination. For the XVI unit, the average dose ranged from 0.1 to 3.5 cGy with the highest dose measured using the "prostate" protocol with the body phantom. For the OBI unit, the average dose ranged from 1.1 to 8.3 cGy with the highest dose measured using the full-fan protocol with the head phantom. The measured doses were highly linear as a function of mA s, for both units, where the measurement points followed a linear relationship very closely with R2 > 0.99 for all cases. Half-value layers were between 4.6- and 7.0-mm-Al for the two CBCT units where XVI generally had more penetrating beams at the similar kVp settings. In conclusion, a comprehensive series of dose measurements were performed on the XVI and the OBI CBCT units. In the process, many of the important similarities and differences between the two systems were observed and summarized in this work.     

Epidemiology of anaphylaxis at a tertiary care center: A report of 730 cases

Background

Recent data reveal that the rate of anaphylaxis is increasing and suggest that idiopathic anaphylaxis may account for most of these cases.

Microwave tomography of extremities: 2. Functional fused imaging of flow reduction and simulated compartment syndrome

Medical imaging has recently expanded into the dual- or multi-modality fusion of anatomical and functional imaging modalities. This significantly improves the diagnostic power while simultaneously increasing the cost of already expensive medical devices or investigations and decreasing their mobility. We are introducing a novel imaging concept of four-dimensional (4D) microwave tomographic (MWT) functional imaging: three dimensional (3D) in the spatial domain plus one dimensional (1D) in the time, functional dynamic domain. Instead of a fusion of images obtained by different imaging modalities, 4D MWT fuses absolute anatomical images with dynamic, differential images of the same imaging technology. The approach was successively validated in animal experiments with short-term arterial flow reduction and a simulated compartment syndrome in an initial simplified experimental setting using a dedicated MWT system. The presented fused images are not perfect as MWT is a novel imaging modality at its early stage of the development and ways of reading reconstructed MWT images need to be further studied and understood. However, the reconstructed fused images present clear evidence that microwave tomography is an emerging imaging modality with great potentials for functional imaging.     

Antibody-binding epitope differences in the nucleoprotein of avian and mammalian influenza A viruses

Abstract Influenza virus nucleoprotein (NP) binds to the viral genome RNA and forms the internal ribonucleoprotein complex of the virus particle. Avian and human influenza virus NP have characteristic differences at several amino acid positions. It is not known whether any of these differences can be recognized by antibodies. In the present study five monoclonal antibodies (MAbs) were produced against NP of A/Duck/Novosibirsk/56/05 (H5N1) influenza virus. Two MAbs discerned human and avian influenza strains on ELISA testing. The NP expressed in a prokaryotic system was used for the analysis of site-specific mutants carrying amino acid substitutions in the relevant positions. Amino acid residues in positions 100 and 101 were shown to be recognized by the MAbs. The residue in position 100 is host-specific, and its recognition by the MAb 2E6 may be useful for the differentiation of human and avian viruses. The data are discussed in view of the effects of amino acid substitutions in influenza virus NP affecting both host range and antibody-binding specificity.     

Elementary receptor currents elicited by a single pheromone molecule exhibit quantal composition

Responses to single pheromone molecules, elementary receptor currents (ERC), recorded from antennal olfactory receptor neurones of the moth Bombyx mori were studied in situ, at the opened sensilla, using the voltage-clamp technique in transepithelial recordings. The amplitude parameters of the ERCs eliciting one action potential in the bombykol and bombykal receptor neurones were analysed. The ERC amplitude varied largely within a range of 0.5-5.5 pA. The amplitude histograms of the ERCs exhibited a series of peaks and shoulders. Quantal analysis of the amplitude distributions based on spectral methods revealed that a quantum event underlies the ERCs. Deconvolution of the ERC amplitude distributions using the distribution of baseline noise indicates that the ERCs exhibit discrete amplitude levels. The weighted average interval between the levels indicates that the quantal size is 0.6-0.7 pA.     

Immunohistochemical evaluation of the protein expression of nerve growth factor and its TrkA receptor in rat limbic regions following electroshock seizures

Repeated (but not acute) exposure to brief, non-injurious seizures evoked by minimal electroconvulsive shock (ECS) decreases neuronal death in limbic system and increases mRNA levels for nerve growth factor (NGF). Thus, the induction of NGF is a potential mechanism for the neuroprotection evoked by repeated ECS. The neuroprotective action of NGF is mediated by the TrkA receptor. This study determined whether repeated ECS exposure increased TrkA and NGF protein levels. To determine the functional significance of changes in these proteins, we compared the effects of ECS given daily either for 7 days (chronic ECS) or for 1 day (acute ECS). After chronic ECS, upregulation of both NGF and TrkA was found in perirhinal cortex, thalamus, and amygdala. In hippocampus, TrkA was upregulated in CA2, CA3 and CA4. NGF increase in hippocampus was found in CA1 and dentate gyrus. In frontal cortex and substantia innominata, an increase in NGF (but not in TrkA) was found. In most brain regions, TrkA and NGF remained unchanged after acute ECS. Our results demonstrate that repeated exposure to ECS causes an upregulation of TrkA and NGF proteins in several limbic areas in which neuroprotective effects are observed suggesting that NGF contributes to ECS-evoked neuroprotection.