Autoantibody systems in rheumatoid arthritis: specificity, sensitivity and diagnostic value

The diagnosis of rheumatoid arthritis (RA) is primarily based on clinical symptoms, so it is often difficult to diagnose RA in very early stages of the disease. A disease-specific autoantibody that could be used as a serological marker would therefore be very useful. Most autoimmune diseases are characterized by a polyclonal B-cell response targeting multiple autoantigens. These immune responses are often not specific for a single disease. In this review, the most important autoantibody/autoantigen systems associated with RA are described and their utility as a diagnostic and prognostic tool, including their specificity, sensitivity and practical application, is discussed. We conclude that, at present, the antibody response directed to citrullinated antigens has the most valuable diagnostic and prognostic potential for RA.     

Bestimmung von deoxynivalenol mittels LC - MS/MS (Tandem Massenspektrometrie)

A sensitive and selective method using high-performance liquid chromatography in combination with atmospheric pressure chemical ionization tandem mass spetrometry (LC-APCI-MS/MS) has been developed for the determination of Deoxynivalenol (DON) in trace levels. The extract was purified with a MultiSep? column followed by the Vicam? DON immunoaffinity column. Quantification is based on an external standard method using positive Multiple Reaction Monitoring (MRM). The limit of detection was 5 μg/kg with a signal to noise ratio of 3:1.     

Foveal information processing at photopic luminances

Summary A tentative model of information processing in the human fovea at photopic luminances is described, that handles both luminosity and chromaticity signals. The model consists of a scaling-ensemble, a group of sealers with common scaling-factor that provide an effective compression of the dynamic range of the input signals. The scaling factor adapts in such a way that the model conforms to Weber's law for the detection of short, small flashes on a bright background. The dynamics of the adaptation is such that the model effectively computes the logarithmic time derivative of the input signal. The model predicts the outcome of several psychophysical experiments. The predictions include Weber's law, Bloch's law, the apparent brightness of suprathreshold flashes as a function of adaptation level, the influence of spatial inhomogeneities on the perception of flicker, and the transfer function for moving sinusoidal bar patterns for both luminosity and chromaticity modulations. The influence of involuntary eye-movements on the perception of spatial patterns is also discussed. Finally an attempt is made to locate the components of the model in the anatomical structure of the retina. A tentative scheme of neural connections in the human fovea is presented.     

The concepts of scaling and refractoriness in psychophysical theories of vision

Summary In the context of the quantum theory of vision scalers, coincidence scalers, adapting coincidence scalers and dead time mechanisms have been used as basic constituents of network models: van de Grind et al. (1970a), Koenderink et al. (1970a, b). The possibilities that these devices offer to construct network models of vision are presently further analysed. First of all a mechanistic analysis is given of the event rate reduction characteristics of dead time boxes. Next the interaction of these devices with scalers is discussed in relation with a number of fluctuation models of vision proposed in the literature. A critical evaluation of these fluctuation models shows an important defect of most of them, viz. that unrealizable detection criteria are postulated. Our reconsideration of this detection problem then leads to the proposal of some specific realizable detectors. An application of the developed theory of mechanisms (machines) to the explanation of the flash detection characteristics of Limulus concludes the paper. Applications of the presented ideas to neural theory and modelling are treated hi a separate paper (van de Grind et al., 1970b) and for applications of the theory to psychophysically oriented visual modelling studies the reader is referred to Koenderink et al. (1970a, b) and van de Grind et al. (1970a).     

Functional changes in human leukemic cell line HL-60. A model for myeloid differentiation

Polar solvents induce terminal differentiation in the human promyelocytic leukemia cell line HL-60. The present studies describe the functional changes that accompany the morphologic progression from promyelocytes to bands and poly-morphonuclear leukocytes (PMN) over 9 d of culture in 1.3 percent dimethylsulfoxide (DMSO). As the HL-60 cells mature, the rate of O(2-) production increase 18-fold, with a progressive shortening of the lag time required for activation. Hexosemonophosphate shunt activity rises concomitantly. Ingestin of paraffin oil droplets opsonized with complement or Ig increases 10-fold over 9 d in DMSO. Latex ingestion per cell by each morphologic type does not change significantly, but total latex ingestion by groups of cells increases with the rise in the proportion of mature cells with greater ingestion capacities. Degranulation, as measured by release of β-glucuronidase, lysozyme, and peroxidase, reaches maximum after 3-6 d in DMSO, then declines. HL-60 cells contain no detectable lactoferrin, suggesting that their secondary granules are absent or defective. However, they kill staphylococci by day 6 in DMSO. Morphologically immature cells (days 1-3 in DMSO) are capable of O(2-) generation, hexosemonophosphate shunt activity, ingestion, degranulation, and bacterial killing. Maximal performance of each function by cells incubated in DMSO for longer periods of time is 50-100 percent that of normal PMN. DMSO- induced differentiation of HL-60 cells is a promising model for myeloid development.     

Computing approximate standard errors for genetic parameters derived from random regression models fitted by average information REML

Approximate standard errors (ASE) of variance components for random regression coefficients are calculated from the average information matrix obtained in a residual maximum likelihood procedure. Linear combinations of those coefficients define variance components for the additive genetic variance at given points of the trajectory. Therefore, ASE of these components and heritabilities derived from them can be calculated. In our example, the ASE were larger near the ends of the trajectory.     

The effects of tensile-compressive loading mode and microarchitecture on microdamage in human vertebral cancellous bone

The amount of microdamage in bone tissue impairs mechanical performance and may act as a stimulus for bone remodeling. Here we determine how loading mode (tension vs. compression) and microstructure (trabecular microarchitecture, local trabecular thickness, and presence of resorption cavities) influence the number and volume of microdamage sites generated in cancellous bone following a single overload. Twenty paired cylindrical specimens of human vertebral cancellous bone from 10 donors (47–78 years) were mechanically loaded to apparent yield in either compression or tension, and imaged in three dimensions for microarchitecture and microdamage (voxel size 0.7×0.7×5.0 μm³). We found that the overall proportion of damaged tissue was greater (p=0.01) for apparent tension loading (3.9±2.4%, mean±SD) than for apparent compression loading (1.9±1.3%). Individual microdamage sites generated in tension were larger in volume (p<0.001) but not more numerous (p=0.64) than sites in compression. For both loading modes, the proportion of damaged tissue varied more across donors than with bone volume fraction, traditional measures of microarchitecture (trabecular thickness, trabecular separation, etc.), apparent Young?s modulus, or strength. Microdamage tended to occur in regions of greater trabecular thickness but not near observable resorption cavities. Taken together, these findings indicate that, regardless of loading mode, accumulation of microdamage in cancellous bone after monotonic loading to yield is influenced by donor characteristics other than traditional measures of microarchitecture, suggesting a possible role for tissue material properties.     

ArrayIDer: automated structural re-annotation pipeline for DNA microarrays

Background  

Systems biology modeling from microarray data requires the most contemporary structural and functional array annotation. However, microarray annotations, especially for non-commercial, non-traditional biomedical model organisms, are often dated. In addition, most microarray analysis tools do not readily accept EST clone names, which are abundantly represented on arrays. Manual re-annotation of microarrays is impracticable and so we developed a computational re-annotation tool (ArrayIDer) to retrieve the most recent accession mapping files from public databases based on EST clone names or accessions and rapidly generate database accessions for entire microarrays.