Allgemeine Pathologie und pathologische Anatomie

Ohne Zusammenfassung     

Developments in the immunophenotypic analysis of haematological malignancies

Immunophenotyping is the method by which antibodies are used to detect cellular antigens in clinical samples. Although the major role is in the diagnosis and classification of haematological malignancies, applications have expanded over the past decade. Immunophenotyping is now used extensively for disease staging and monitoring, to detect surrogate markers of genetic aberrations, to identify potential immuno-therapeutic targets and to aid prognostic prediction. This expansion in applications has resulted from developments in antibodies, methodology, automation and data handling. In this review we describe recent advances in both the technology and applications for the analysis of haematological malignancies. We highlight the importance of the expanding repertoire of testing capability for diagnostic, prognostic and therapeutic applications. The impact and significance of immunophenotyping in the assessment of haematological neoplasms are evident.     

The effect of immersion cryotherapy on medial‐lateral postural sway variability in individuals with a lateral ankle sprain

Background and Purpose . Postural stability has been shown to be impaired after a lateral ankle sprain (LAS) and after immersion cryotherapy in healthy ankles. This study was performed to determine the effects of cryotherapy on postural stability after LAS. Method . A single‐session, repeated measures design was used. Fifteen 18‐ to 29‐year‐old males (mean age 21.33 ± 3.54, height 71.23 ± 2.50 cm, mass 170.33 ± 19.77 kg) with relatively recent grade I LAS volunteered. Medial‐lateral postural sway variability was assessed during single‐leg barefoot stance using a Bertec force platform. Sway was tested before cryotherapy (‘Pre’), immediately after 20 minutes of lower‐leg immersion cryotherapy (‘Post₀’), and 10 and 20 minutes after cryotherapy (‘Post₁₀’ and ‘Post₂₀’). Both legs were tested (individually) before cryotherapy; the involved leg was tested alone after cryotherapy. The uninvolved leg served as a control. Results . Postural sway variability of the involved le was significantly greater than the uninvolved le before cryotherapy (p = 0.001). Postural sway variability of the involved le was also significantly greater than the uninvolved LE during Post₀ (p = 0.000), Post₁₀ (p = 0.000) and Post₂₀ testing (p = 0.003) with the largest increase in sway variability occurring at Post₀. Conclusions . Medial‐lateral postural sway variability was greater after LAS. This effect was augmented by immersion cryotherapy. Copyright © 2008 John Wiley & Sons, Ltd.     

Accidental organophosphate insecticide intoxication in children: a reminder

Misuse of organophosphate insecticides, even in case of domestic application, can be life threatening. We report the case of siblings admitted with respiratory distress, pinpoint pupils and slurred speech. The symptoms appear after spraying the skin by insecticides. Plasma pseudocholinesterase level appeared to be very low, consistent with acute intoxication with organophosphate insecticide.Management of organophosphate poisoning consists of airway management, administration of oxygen and fluid, as well as atropine in increasing doses and pralidoxime. Decontamination of the patient's skin and the removal of the patient's clothes are mandatory in order to avoid recontamination of the patient as well as the surrounding healthcare personnel.Plasma pseudocholinesterase analysis is a cheap and an easy indicator for organophosphate insecticides intoxications and could be used for diagnosis and treatment monitoring.     

Comparative methylomics reveals gene-body H3K36me3 in Drosophila predicts DNA methylation and CpG landscapes in other invertebrates

In invertebrates that harbor functional DNA methylation enzymatic machinery, gene-bodies are the primary targets for CpG methylation. However, virtually all other aspects of invertebrate DNA methylation have remained a mystery until now. Here, using a comparative methylomics approach, we demonstrate that Nematostella vectensis, Ciona intestinalis, Apis mellifera, and Bombyx mori show two distinct populations of genes differentiated by gene-body CpG density. Genome-scale DNA methylation profiles for A. mellifera spermatozoa reveal CpG-poor genes are methylated in the germline, as predicted by the depletion of CpGs. We find an evolutionarily conserved distinction between CpG-poor and GpC-rich genes: The former are associated with basic biological processes, the latter with more specialized functions. This distinction is strikingly similar to that recently observed between euchromatin-associated genes in Drosophila that contain intragenic histone 3 lysine 36 trimethylation (H3K36me3) and those that do not, even though Drosophila does not display CpG density bimodality or methylation. We confirm that a significant number of CpG-poor genes in N. vectensis, C. intestinalis, A. mellifera, and B. mori are orthologs of H3K36me3-rich genes in Drosophila. We propose that over evolutionary time, gene-body H3K36me3 has influenced gene-body DNA methylation levels and, consequently, the gene-body CpG density bimodality characteristic of invertebrates that harbor CpG methylation.     

NOD2 activity modulates the phenotype of LPS-stimulated dendritic cells to promote the development of T-helper type 2-like lymphocytes — Possible implications for NOD2-associated Crohn''s disease

Sensing of commensal microorganisms via Toll-like receptors (TLR) in the gut is essential for maintaining intestinal homeostasis in healthy individuals. Conversely, Crohn's disease is characterised by an inappropriate T helper-type 1 (Th1)-mediated immune response towards these same microorganisms. NOD2 is expressed by dendritic cells (DC) and mediates responses to bacterial muramyl-dipeptides (MDP). Mutations in NOD2 (CARD15) have recently been associated with susceptibility to Crohn's disease although the underlying mechanisms have yet to be established. We investigated the functional outcome of NOD2 and TLR4-mediated activation in monocyte-derived DC from wild-type NOD2 healthy controls and NOD2 frame-shift mutation-carrying Crohn's disease patients. In wild-type DC, MDP acted synergistically with LPS to amplify inflammatory cytokine production, enhance co-stimulatory molecule expression, and produce DC that promoted the proliferation of naïve, allogeneic, CD4⁺ T lymphocytes with a Th2-like cytokine profile. By contrast, DC carrying homozygous NOD2 mutations were unable to react to MDP, responded to LPS only, and promoted the development of Th1 cells. These results suggest activation of the NOD2 pathway in DC modulates their response to TLR agonists and regulates their ability to induce polarised Th1 responses. As a consequence, Crohn's disease patients with defective NOD2 may be predisposed to the generation of strongly polarised Th1 responses against common commensal microorganisms.     

Genetics in coeliac disease

Coeliac disease has a strong genetic component, higher than for many other common complex diseases. Possession of the HLA-DQ2 variant is required for presentation of disease causing dietary antigens to T cells, although this is also common in the healthy population. Non-HLA genetic factors account for the majority of heritable risk. Linkage studies have identified promising regions on chromosomes 5 and 19, with multiple other loci awaiting definitive confirmation in independent studies. Inherited variants in the tightly clustered chromosome 2q CD28-CTLA4-ICOS region are associated with disease, although of weak effect size. Larger sample sizes are necessary in coeliac disease genetic studies to detect small effects, alternatively meta-analysis offers promise. Newer methods including gene expression analysis and genome wide association studies will advance understanding of genetic susceptibility. Identification of coeliac disease genes may improve diagnostic/prognostic markers, basic understanding of disease aetiology, permit development of novel therapeutics and provide insight into other autoimmune disorders.