A new histology scoring system for the assessment of the quality of human cartilage repair: ICRS II

A reliable and reproducible method is needed to assess cartilage repair.

Primer extension based quantitative polymerase chain reaction reveals consistent differences in the methylation status of the MGMT promoter in diffusely infiltrating gliomas (WHO grade II-IV) of adults

Diffusely infiltrating gliomas (WHO grade II-IV) are the most common primary brain tumours in adults. These tumours are not amenable to cure by surgery alone, so suitable biomarkers for adjuvant modalities are required to guide therapeutic decision-making. Epigenetic silencing of the O(6)-methylguanine-DNA methyltransferase (MGMT) gene by promoter methylation has been associated with longer survival of patients with high-grade gliomas who receive alkylating chemotherapy; and molecular testing for the methylation status of the MGMT promoter sequence is regarded as among the most relevant of such markers. We have developed a primer extension-based assay adapted to formalin-fixed paraffin-embedded tissues that enables quantitative assessment of the methylation status of the MGMT promoter. The assay is very sensitive, highly reproducible, and provides valid test results in nearly 100% of cases. Our results indicate that oligodendrogliomas, empirically known to have a relatively favourable prognosis, are also the most homogeneous entities in terms of MGMT promoter methylation. Conversely, astrocytomas, which are more prone to spontaneous progression to higher grade malignancy, are significantly more heterogeneous. In addition, we show that the degree of promoter methylation correlates with the prevalence of loss of heterozygosity on chromosome arm 1p in the oligodendroglioma group, but not the astrocytoma group. Our results may have potentially important implications for clinical molecular diagnosis.

Primary tumors of the submandibular glands: a retrospective study based on 41 cases

We report our experience on the diagnostic approach, treatment, and follow-up of primary submandibular gland tumors. Retrospective review. Tertiary referral center. Forty-one adult patients, 22 male and 19 female, with primary submandibular gland tumors, 20 benign and 21 malignant. Age, gender, clinical findings, cyto- and histopathology, treatment and outcome were analyzed. Most tumors presented as a painless submandibular mass. Thirty three patients underwent a fine needle aspiration, the sensitivity, specificity and accuracy of which--in detecting malignant tumors--were 79%, 100% and 88%, respectively. Preoperative radiological imaging was performed in 30 cases. Patients with benign tumors were treated with surgery. Most malignant tumors were treated with a combined modality, including neck dissection and radiation therapy. Five patients developed a postoperative complication. Recurrent disease was encountered in 5 malignant tumors. The 2, 5 and 10 year disease-specific survival of patients with malignancy were 84%, 75% and 41%, respectively. The preoperative assessment of the nature of submandibular gland tumors remains challenging. Aggressive treatment of patients with malignant disease may help to avoid poor prognosis.

Über die Bedeutsamkeit linguistischen Wissens im privatwirtschaftlichen Arbeitsfeld

Until today, linguistics as an academic field does not aim at responding to the expectations of the job market. However, on the backdrop of an increasing interrelation of politics, economy and science, questions as to the applicability of linguistics to labour processes and the employability of linguists are raised and need to be answered. In analysing data gained in the course of 21 interviews conducted with linguists working in the private sector of economy, several issues have shown to be of major interest. This paper addresses firstly in what ways linguistics was likely to be seen as relevant for the jobs held by the various interviewees from the point of view of their employers, which is then compared to the interviewees' own evaluations on the relevance of linguistic knowledge for their daily work. On the one hand it becomes clear that there are differences between the three comparable situations in which the analysed transfer of knowledge takes place (Quereinstieg, Schnittstellenjob, "sprachperformativer Job"). One the other hand linguistic expertise in the extra-academic field seems to be most salient or approved of when it comes to language competence in text production or communicative situations, which further complicates the attempt to make linguistics transparent for non-linguists.

Report from a consensus conference on antibody-mediated rejection in heart transplantation

The problem of AMR remains unsolved because standardized schemes for diagnosis and treatment remains contentious. Therefore, a consensus conference was organized to discuss the current status of antibody-mediated rejection (AMR) in heart transplantation.

Crosstalk between B lymphocytes, microbiota and the intestinal epithelium governs immunity versus metabolism in the gut

Using a systems biology approach, we discovered and dissected a three-way interaction between the immune system, the intestinal epithelium and the microbiota. We found that, in the absence of B cells, or of IgA, and in the presence of the microbiota, the intestinal epithelium launches its own protective mechanisms, upregulating interferon-inducible immune response pathways and simultaneously repressing Gata4-related metabolic functions. This shift in intestinal function leads to lipid malabsorption and decreased deposition of body fat. Network analysis revealed the presence of two interconnected epithelial-cell gene networks, one governing lipid metabolism and another regulating immunity, that were inversely expressed. Gene expression patterns in gut biopsies from individuals with common variable immunodeficiency or with HIV infection and intestinal malabsorption were very similar to those of the B cell-deficient mice, providing a possible explanation for a longstanding enigmatic association between immunodeficiency and defective lipid absorption in humans.

Effects of changes in colored light on brain and calf muscle blood concentration and oxygenation

Color light therapy is a therapeutic method in complementary medicine. In color therapy, light of two contrasting colors is often applied in a sequential order. The aim of this study was to investigate possible physiological effects, i.e., changes in the blood volume and oxygenation in the brain and calf muscle of healthy subjects who were exposed to red and blue light in sequential order. The hypothesis was that if a subject is first exposed to blue and then red light, the effect of the red light will be enhanced due to the contrastingly different characteristics of the two colors. The same was expected for blue light, if first exposing a subject to red and then to blue light. Twelve healthy volunteers (six male, six female) were measured twice on two different days by near-infrared spectroscopy during exposure to colored light. Two sequences of colored light were applied in a controlled, randomized, crossover design: first blue, then red, and vice versa. For the brain and muscle, the results showed no significant differences in blood volume and oxygenation between the two sequences, and a high interindividual physiological variability. Thus, the hypothesis had to be rejected. Comparing these data to results from a previous study, where subjects were exposed to blue and red light without sequential color changes, shows that the results of the current study appear to be similar to those of red light exposure. This may indicate that the exposure to red light was preponderant and thus effects of blue light were outweighed.

Antimicrobial activities of chemokines: not just a side-effect?

The large family of chemoattractant cytokines (chemokines) embraces multiple, in part unrelated functions that go well beyond chemotaxis. Undoubtedly, the control of immune cell migration (chemotaxis) is the single, unifying response mediated by all chemokines, which involves the sequential engagement of chemokine receptors on migrating target cells. However, numerous additional cellular responses are mediated by some (but not all) chemokines, including angiogenesis, tumor cell growth, T-cell co-stimulation, and control of HIV-1 infection. The recently described antimicrobial activity of several chemokines is of particular interest because antimicrobial peptides are thought to provide an essential first-line defense against invading microbes at the extremely large body surfaces of the skin, lungs, and gastrointestinal-urinary tract. Here we summarize the current knowledge about chemokines with antimicrobial activity and discuss their potential contribution to the control of bacterial infections that may take place at the earliest stage of antimicrobial immunity. In the case of homeostatic chemokines with antimicrobial function, such as CXCL14, we propose an immune surveillance function in healthy epithelial tissues characterized by low-level exposure to environmental microbes. Inflammatory chemokines, i.e., chemokines that are produced in tissue cells in response to microbial antigens (such as pathogen-associated molecular patterns) may be more important in orchestrating the cellular arm in antimicrobial immunity.

Function of liver activation-regulated chemokine/CC chemokine ligand 20 is differently affected by cathepsin B and cathepsin D processing

Chemokine processing by proteases is emerging as an important regulatory mechanism of leukocyte functions and possibly also of cancer progression. We screened a large panel of chemokines for degradation by cathepsins B and D, two proteases involved in tumor progression. Among the few substrates processed by both proteases, we focused on CCL20, the unique chemokine ligand of CCR6 that is expressed on immature dendritic cells and subtypes of memory lymphocytes. Analysis of the cleavage sites demonstrate that cathepsin B specifically cleaves off four C-terminally located amino acids and generates a CCL20(1-66) isoform with full functional activity. By contrast, cathepsin D totally inactivates the chemotactic potency of CCL20 by generating CCL20(1-55), CCL20(1-52), and a 12-aa C-terminal peptide CCL20(59-70). Proteolytic cleavage of CCL20 occurs also with chemokine bound to glycosaminoglycans. In addition, we characterized human melanoma cells as a novel CCL20 source and as cathepsin producers. CCL20 production was up-regulated by IL-1alpha and TNF-alpha in all cell lines tested, and in human metastatic melanoma cells. Whereas cathepsin D is secreted in the extracellular milieu, cathepsin B activity is confined to cytosol and cellular membranes. Our studies suggest that CCL20 processing in the extracellular environment of melanoma cells is exclusively mediated by cathepsin D. Thus, we propose a model where cathepsin D inactivates CCL20 and possibly prevents the establishment of an effective antitumoral immune response in melanomas.

Papillary glioneuronal tumor

The descriptive term papillary glioneuronal tumor (PGNT) has been repeatedly applied to a morphologic subset of low-grade mixed glial-neuronal neoplasia of juvenile and young adult patients. We report on a 13-year-old boy with PGNT of the left temporal lobe, who presented with headaches and a single generalized seizure. On magnetic resonance imaging, tumor was seen as a large, moderately enhancing paraventricular mass with cyst-mural nodule configuration and slight midline shift. Perifocal edema was virtually absent. Gross total resection could be performed, followed by an uneventful recovery. Histologically, the tumor exhibited similar, if not identical, features as reported previously. These comprised a patterned biphasic mixture of sheets of synaptophysin-expressing small round cells and pseudorosettes of GFAP-positive rudimentary astrocytes along vascular cores. Focally, the latter imprinted a pseudopapillary aspect on this otherwise solid lesion. Both cellular components expressed non-polysialylated neural cell adhesion molecule (NCAM)-L species, and several overlapping areas of synaptophysin and GFAP immunoreactivity were present. The mean MIB-1 labeling index remained below 1%. Signs of anaplasia, in particular mitotic figures, endothelial proliferation, or necrosis were consistently lacking. We perceive PGNT as a clinically and morphologically well-delineated subgroup of extraventricular neurocytic neoplasia, whose paradigmatic presentation may allow for consideration as an entity.