Studies on the pathogenesis of ischemic cell injury. XI. P/O ratio and acceptor control.

Acceptor control index, P/O ratio and inner membrane permeability were examined in isolated mitochondria following periods of renal ischemia for 15, 30, 60, 120, and 240 min. It was noted that the P/O ratio remained unchanged until 1-2 h after the onset of ischemia. A similar change was noted in the contraction rate of isolated ischemic mitochondria after swelling in KCl and addition of ATP+Mg2+. Both changes are probably indications of a basic membrane alteration which correlates with the occurrence of irreversibility of cell injury. In contrast, the swelling rate in KCl and the acceptor control index are altered almost simultaneously with the onset of ischemia. Therefore, acceptor control index and the rate of swelling are affected prior to the point of irreversible cell injury. They are not, therefore, good as indicators of irreversible changes in the inner membrane of mitochondria leading to the "point-of-no-return."     

Synovial explant inflammatory mediator production corresponds to rheumatoid arthritis imaging hallmarks: a cross-sectional study

Introduction

Despite the widespread use of magnetic resonance imaging (MRI) and Doppler ultrasound for the detection of rheumatoid arthritis (RA) disease activity, little is known regarding the association of imaging-detected activity and synovial pathology. The purpose of this study was to compare site-specific release of inflammatory mediators and evaluate the corresponding anatomical sites by examining colour Doppler ultrasound (CDUS) and MRI scans.

Methods

RA patients were evaluated on the basis of CDUS and 3-T MRI scans and subsequently underwent synovectomy using a needle arthroscopic procedure of the hand joints. The synovial tissue specimens were incubated for 72 hours, and spontaneous release of monocyte chemoattractant protein 1 (MCP-1), interleukin 6 (IL-6), macrophage inflammatory protein 1β (MIP-1β) and IL-8 was measured by performing multiplex immunoassays. Bone marrow oedema (BME), synovitis and erosion scores were estimated on the basis of the rheumatoid arthritis magnetic resonance imaging score (RAMRIS). Mixed models were used for the statistical analyses. Parsimony was achieved by omitting covariates with P > 0.1 from the statistical model.

Results

Tissue samples from 58 synovial sites were obtained from 25 patients. MCP-1 was associated with CDUS activity (P = 0.009, approximate Spearman’s ρ = 0.41), RAMRIS BME score (P = 0.01, approximate Spearman’s ρ = 0.42) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.31). IL-6 was associated with RAMRIS synovitis score (P = 0.04, approximate Spearman’s ρ = 0.50), BME score (P = 0.04, approximate Spearman’s ρ = 0.31) and RAMRIS erosion score (P = 0.03, approximate Spearman’s ρ = 0.35). MIP-1β was associated with CDUS activity (P = 0.02, approximate Spearman’s ρ = 0.38) and RAMRIS synovitis scores (P = 0.02, approximate Spearman’s ρ = 0.63). IL-8 associations with imaging outcome measures did not reach statistical significance.

Conclusions

The association between imaging activity and synovial inflammatory mediators underscores the high sensitivity of CDUS and MRI in the evaluation of RA disease activity. The associations found in our present study have different implications for synovial mediator releases and corresponding imaging signs. For example, MCP-1 and IL-6 were associated with both general inflammation and bone destruction, in contrast to MIP-1β, which was involved solely in general synovitis. The lack of association of IL-8 with synovitis was likely underestimated because of a large proportion of samples above assay detection limits among the patients with the highest synovitis scores.     

Microprobe analysis and fine structure of mitochondrial granules in ultrathin frozen sections of rat pancreas

High resolution electron microscopy and microprobe analysis studies on untreated frozen sections of normal pancreas reveal a distinct appearance of mitochondrial granules. These granules have been shown to contain a significant amount of calcium and potassium. Based upon these findings, it is proposed that normal mitochondrial granules represent special sites for cation storage and release since these structures are quite labile in contrast to the abnormal accumulation of divalent cations in loading experiments.     

Quantitative Analyse von Korallengemeinschaften des Sanganeb-Atolls (mittleres Rotes Meer). I. Die Besiedlungsstruktur hydrodynamisch unterschiedlich exponierter Außen- und Innenriffe

The Sanganeb-Atoll off Port Sudan is an elongate annular reef which rests on a probably raised block in the fracture zone along the Red Sea-graben. Its gross morphology was most likely formed by subaerial erosion during low sealevel conditions. Features of its topography and hydrography are described. The prevailing wind waves are from NE, Hence, the outer and inner reef slopes are exposed to different hydrodynamic conditions. The sessile benthos was analysed using the quadrat method. Four test quadrats (5×5 m each) were selected on the outer and inner slopes at a depth of 10 m along a SSW-NNE transect across the atoll. Cnidaria were by far the most dominating group; coralline algae, Porifera, Bryozoa and Ascidia, however, counted for just under 3 % living cover. Light and temperature intensities did not differ significantly at the sites studied; water movement, however, decreased in the following order: TQ IV (outer NE side of the reef ring) was exposed to strong swell and surf; TQ II (inner side of the SW-ring) was met by a strong longreef current; TQ I was situated on the outer lee of the SW-atoll ring and TQ III in the inner lee of the NE-side. This hydrodynamic gradient correlates with the composition of the coral communities from predominantly branching Scleractinia (staghorn-like and otherAcropora species andPocillopora) in TQ IV, through aLobophyllia, Porites andXenia-dominated community in TQ II, and a mixed community with an increasing percentage of xeniid and alcyoniid soft corals in TQ I, to a community in TQ III which is dominated by the soft coralsSinularia andDendronephthya. The cnidarian cover ranged between 42.4 and 56.6 % whereby the two exposed test quadrats had a higher living coverage than the protected ones. In total, 2649 colonies comprising 124 species of stony, soft and hydrocorals were recorded by an elaborate method of accurate in-situ mapping. The 90 scleractinian species found include 3 species new to the Red Sea and 11 hitherto unknown species from its central part. Only 7 cnidarian species covered large areas, forming aXenia macrospiculata-zone in TQ I, a Lobophyllia corymbosa-zone in TQ II, aSinularia-Dendronephthya-zone in TQ III and anAcropora-Pocillopora verrucosa-zone in TQ IV. Hydrodynamic exposition and ratio of genus abundanceAcropora: Montipora are closely correlated: on the windward side (TQ IV) it is 943:4, but on the leeward side (TQ I) 18:208. Apart from the taxonomic and quantitative distribution of species and colonies, types of growth form and categories of the dead substrate are given. Since soft corals do not contribute to the reef framework, the distribution of Scleractinia and Alcyonaria indicates that at Sanganeb-Atoll reef substance is mainly generated on the windward side.     

Vestibular humanoid postural control

Many of our motor activities require stabilization against external disturbances. This especially applies to biped stance since it is inherently unstable. Disturbance compensation is mainly reactive, depending on sensory inputs and real-time sensor fusion. In humans, the vestibular system plays a major role. When there is no visual space reference, vestibular-loss clearly impairs stance stability. Most humanoid robots do not use a vestibular system, but stabilize upright body posture by means of center of pressure (COP) control. We here suggest using in addition a vestibular sensor and present a biologically inspired vestibular sensor along with a human-inspired stance control mechanism. We proceed in two steps. First, in an introductory review part, we report on relevant human sensors and their role in stance control, focusing on own models of transmitter fusion in the vestibular sensor and sensor fusion in stance control. In a second, experimental part, the models are used to construct an artificial vestibular system and to embed it into the stance control of a humanoid. The robot’s performance is investigated using tilts of the support surface. The results are compared to those of humans. Functional significance of the vestibular sensor is highlighted by comparing vestibular-able with vestibular-loss states in robot and humans. We show that a kinematic body-space sensory feedback (vestibular) is advantageous over a kinetic one (force cues) for dynamic body-space balancing. Our embodiment of human sensorimotor control principles into a robot is more than just bionics. It inspired our biological work (neurorobotics: ‘learning by building’, proof of principle, and more). We envisage a future clinical use in the form of hardware-in-the-loop simulations of neurological symptoms for improving diagnosis and therapy and designing medical assistive devices.     

Does evaluation of the ligamentous compartment enhance diagnostic utility of sacroiliac joint MRI in axial spondyloarthritis?

IntroductionInflammation of the sacroiliac joints (SIJ) is a fundamental clinical feature of axial spondyloarthritis (SpA). The anatomy of the irregularly shaped SIJ is complex with an antero-inferior cartilaginous compartment containing central hyaline and peripheral fibrocartilage, and a dorso-superior ligamentous compartment. Several scoring modules to systematically assess SIJ magnetic resonance imaging (MRI) in SpA have been developed. Nearly all of them are based on the cartilaginous joint compartment alone. However, there are only limited data about the frequency of inflammatory lesions in the ligamentous compartment and their potential diagnostic utility in axial SpA. We therefore aimed to evaluate the ligamentous compartment on sacroiliac joint MRI for lesion distribution and potential incremental value towards diagnosis of SpA over and above the traditional assessment of the cartilaginous compartment alone.MethodsTwo independent cohorts of 69 and 88 consecutive back pain patients ≤50 years were referred for suspected SpA (cohort A) or acute anterior uveitis plus back pain (cohort B). Patients were classified according to rheumatologist expert opinion based on clinical, radiographic and laboratory examination as having nonradiographic axial SpA (nr-axSpA; n = 51), ankylosing spondylitis (n = 34), or nonspecific back pain (NSBP; n = 72). Five blinded readers assessed SIJ MRI globally for presence/absence of SpA. Bone marrow edema (BME) and fat metaplasia were recorded in the cartilaginous and ligamentous compartment. The incremental value of evaluating the ligamentous additionally to the cartilaginous compartment alone for diagnosis of SpA was graded qualitatively. We determined the lesion distribution between the two compartments, and the impact of the ligamentous compartment evaluation on diagnostic utility.ResultsMRI bone marrow lesions solely in the ligamentous compartment in the absence of lesions in the cartilaginous compartment were reported in just 0–2.0/0–4.0 % (BME/fat metaplasia) of all subjects. Additional assessment of the ligamentous compartment was regarded as essential for diagnosis in 0 and 0.6 %, and as contributory in 28.0 and 7.7 % of nr-axSpA patients in cohorts A and B, respectively. Concomitant BME in both compartments was evident in 11.6–42.0 % of nr-axSpA and 2.1–2.4 % of NSBP patients.ConclusionAssessing the ligamentous compartment on SIJ MRI provided no incremental value for diagnosis of axial SpA. However, concomitant BME in both compartments may help discriminate nr-axSpA from NSBP.     

Transcriptomic response to differentiation induction

Background  

Microarrays used for gene expression studies yield large amounts of data. The processing of such data typically leads to lists of differentially-regulated genes. A common terminal data analysis step is to map pathways of potentially interrelated genes.     

The effect of oligonucleotide microarray data pre-processing on the analysis of patient-cohort studies

Background  

Intensity values measured by Affymetrix microarrays have to be both normalized, to be able to compare different microarrays by removing non-biological variation, and summarized, generating the final probe set expression values. Various pre-processing techniques, such as dChip, GCRMA, RMA and MAS have been developed for this purpose. This study assesses the effect of applying different pre-processing methods on the results of analyses of large Affymetrix datasets. By focusing on practical applications of microarray-based research, this study provides insight into the relevance of pre-processing procedures to biology-oriented researchers.