Primäres zerebelläres T-Zell-Lymphom

Zusammenfassung: Primäre T-Zell-Lymphome des zentralen Nervensystems (ZNS) sind selten. Sie müssen differenzialdiagnostisch von reaktiven Läsionen unterschieden werden. Die Diagnosestellung sollte integrativ unter Verwendung von immunhistochemischen, molekulargenetischen und/oder zytogenetischen Methoden erfolgen. Wir beschreiben den Fall eines 50-jährigen Mannes, bei welchem ein primäres zerebelläres T-Zell-Lymphom diagnostiziert und eine klonale T-Zell-Rezeptorgen-Umlagerung nachgewiesen wurde. Nach 2Zyklen Chemotherapie entwickelte der Patient eine Pneumozystis-carinii-Pneumonie und verstarb 10Wochen nach Diagnosestellung. Die Autopsie ergab keinen Residualtumor im ZN

Segregated tunneling-percolation model for transport nonuniversality

We propose a theory of the origin of transport nonuniversality in disordered insulating-conducting compounds based on the interplay between microstructure and tunneling processes between metallic grains dispersed in the insulating host. We show that if the metallic phase is arranged in quasi-one dimensional chains of conducting grains, then the distribution function of the chain conductivities g has a power-law divergence for g -> 0 leading to nonuniversal values of the transport critical exponent t. We evaluate the critical exponent t by Monte Carlo calculations on a cubic lattice and show that our model can describe universal as well nonuniversal behavior of transport depending on the value of few microstructural parameters. Such segregated tunneling-percolation model can describe the microstructure of a quite vast class of materials known as thick-film resistors which display universal or nonuniversal values of t depending on the composition.Comment: 8 pages, 5 figures (Phys. Rev. B - 1 August 2003)(fig1 replaced

Sediment-Water Interactions Affecting Dissolved-Mercury Distributions in Camp Far West Reservoir, California

Field and laboratory studies were conducted in April and November 2002 to provide the first direct measurements of the benthic flux of dissolved (0.2-micrometer filtered) mercury species (total and methylated forms) between the bottom sediment and water column at three sampling locations within Camp Far West Reservoir, California: one near the Bear River inlet to the reservoir, a second at a mid-reservoir site of comparable depth to the inlet site, and the third at the deepest position in the reservoir near the dam (herein referred to as the inlet, midreservoir and near-dam sites, respectively; Background, Fig. 1). Because of interest in the effects of historic hydraulic mining and ore processing in the Sierra Nevada foothills just upstream of the reservoir, dissolved-mercury species and predominant ligands that often control the mercury speciation (represented by dissolved organic carbon, and sulfides) were the solutes of primary interest. Benthic flux, sometimes referred to as internal recycling, represents the transport of dissolved chemical species between the water column and the underlying sediment. Because of the affinity of mercury to adsorb onto particle surfaces and to form insoluble precipitates (particularly with sulfides), the mass transport of mercury in mining-affected watersheds is typically particle dominated. As these enriched particles accumulate at depositional sites such as reservoirs, benthic processes facilitate the repartitioning, transformation, and transport of mercury in dissolved, biologically reactive forms (dissolved methylmercury being the most bioavailable for trophic transfer). These are the forms of mercury examined in this study. In contrast to typical scientific manuscripts, this report is formatted in a pyramid-like structure to serve the needs of diverse groups who may be interested in reviewing or acquiring information at various levels of technical detail (Appendix 1). The report enables quick transitions between the initial summary information (figuratively at the top of the pyramid) and the later details of methods or results (figuratively towards the base of the pyramid) using hyperlinks to supporting figures and tables, and an electronically linked Table of Contents. During two sampling events, two replicate sediment cores (Coring methods; Fig. 2) from each of three reservoir locations (Fig. 1) were used in incubation experiments to provide flux estimates and benthic biological characterizations. Incubation of these cores provided “snapshots” of solute flux across the sediment-water interface in the reservoir, under benthic, environmental conditions representative of the time and place of collection. Ancillary data, including nutrient and ligand fluxes, were gathered to provide a water-quality framework from which to compare the results for mercury

Context-specific regulation of cell survival by a miRNA-controlled BIM rheostat

Knockout of the ubiquitously expressed miRNA-17~92 cluster in mice produces a lethal developmental lung defect, skeletal abnormalities, and blocked B lymphopoiesis. A shared target of miR-17~92 miRNAs is the pro-apoptotic protein BIM, central to life-death decisions in mammalian cells. To clarify the contribution of miR-17~92:Bim interactions to the complex miR-17~92 knockout phenotype, we used a system of conditional mutagenesis of the nine Bim 3' UTR miR-17~92 seed matches. Blocking miR-17~92:Bim interactions early in development phenocopied the lethal lung phenotype of miR-17~92 ablation and generated a skeletal kinky tail. In the hematopoietic system, instead of causing the predicted B cell developmental block, it produced a selective inability of B cells to resist cellular stress; and prevented B and T cell hyperplasia caused by Bim haploinsufficiency. Thus, the interaction of miR-17~92 with a single target is essential for life, and BIM regulation by miRNAs serves as a rheostat controlling cell survival in specific physiological contexts

Burkitt lymphoma with a granulomatous reaction: an M1/Th1-polarised microenvironment is associated with controlled growth and spontaneous regression

Aims: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma that, in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four such cases, two of which regressed spontaneously. Methods and results: All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein–Barr virus (EBV)-positive with type I latency. Investigation of the TME showed similar features in all four cases. The analysis revealed a proinflammatory response triggered by Th1 lymphocytes and M1 polarised macrophages encircling the neoplastic cells with a peculiar topographic distribution. Conclusions: Our data provide an in-vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights into new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy

MARIS: Method for Analyzing RNA following Intracellular Sorting

Transcriptional profiling is a key technique in the study of cell biology that is limited by the availability of reagents to uniquely identify specific cell types and isolate high quality RNA from them. We report a Method for Analyzing RNA following Intracellular Sorting (MARIS) that generates high quality RNA for transcriptome profiling following cellular fixation, intracellular immunofluorescent staining and FACS. MARIS can therefore be used to isolate high quality RNA from many otherwise inaccessible cell types simply based on immunofluorescent tagging of unique intracellular proteins. As proof of principle, we isolate RNA from sorted human embryonic stem cell-derived insulin-expressing cells as well as adult human β cells. MARIS is a basic molecular biology technique that could be used across several biological disciplines.Howard Hughes Medical InstituteHarvard Stem Cell InstituteNational Institutes of Health (U.S.) (grant 2U01DK07247307)National Institutes of Health (U.S.) (grant RL1DK081184)National Institutes of Health (U.S.) (grant 1U01HL10040804

Burkitt lymphoma with granulomatous reaction: A M1/TH1‐polarized microenvironment associates with controlled growth and spontaneous regression

AIMS: Burkitt lymphoma (BL) is an aggressive B-cell lymphoma, which in some instances, may show a granulomatous reaction associated with a favourable prognosis and occasional spontaneous regression. In the present study, we aimed to define the tumour microenvironment (TME) in four of such cases, two of which regressed spontaneously. METHODS AND RESULTS: All cases showed aggregates of tumour cells with the typical morphology, molecular cytogenetics and immunophenotype of BL surrounded by a florid epithelioid granulomatous reaction. All four cases were Epstein-Barr virus (EBV) positive with type I latency. The investigation of the tumour microenvironment (TME) showed similar features in all four cases. The analysis revealed a pro-inflammatory response triggered by Th1 lymphocytes and M1 polarized macrophages encircling the neoplastic cells with a peculiar topographic distribution. CONCLUSIONS: Our data provide an in vivo picture of the role that specific immune cell subsets might play during the early phase of BL, which may be capable of maintaining the tumour in a self-limited state or inducing its regression. These novel results may provide insights to explore new potential therapeutic avenues in EBV-positive BL patients in the era of cellular immunotherapy

Therapeutic targets and microenvironment in sequential biopsies of classical Hodgkin lymphoma at diagnosis and relapse

Classical Hodgkin lymphoma is dominated by the non-neoplastic microenvironment, while the neoplastic Hodgkin-Reed-Sternberg cells compose only a minority of cells in the lymphoma tissue. Both the Hodgkin-Reed-Sternberg cells due to their expression of CD30 and PD-L1 and the microenvironment with abundant T cells and expression of PD1 are specifically targeted by new treatment concepts. We aimed to understand the dynamics of therapeutic targets in patients treated with conventional chemotherapy. We analyzed sequential biopsy specimens obtained at diagnosis and at relapse from the same patient for morphology, immunophenotype, and microenvironmental components. The morphological subtype changed between primary and relapse biopsy in 20% of cases. The immunophenotype was stable with respect to CD30, CD3, and LMP1 but variable with respect to CD15 and CD20 expression. Gene expression revealed 8 upregulated and 20 downregulated genes at relapse (p <= 0.05) with a consistent logarithmic fold change direction in at least 75% of all cases. For PD1, we found discrepant results between gene expression analysis (decrease at relapse) and number of PD1-positive cells assessed by immunohistochemistry (unchanged at relapse). PD-L1 in the neoplastic cells appeared unchanged between primary diagnosis and relapse. The expression of the therapeutic targets CD30, PD1, and PD-L1 can reliably be assessed in tumor specimen at first diagnosis and is unchanged under conventional chemotherapy

Application of an electronic nose coupled with fuzzy-wavelet network for the detection of meat spoilage

Food product safety is one of the most promising areas for the application of electronic noses. During the last twenty years, these sensor-based systems have made odour analyses possible. Their application into the area of food is mainly focused on quality control, freshness evaluation, shelf-life analysis and authenticity assessment. In this paper, the performance of a portable electronic nose has been evaluated in monitoring the spoilage of beef fillets stored either aerobically or under modified atmosphere packaging, at different storage temperatures. A novel multi-output fuzzy wavelet neural network model has been developed, which incorporates a clustering pre-processing stage for the definition of fuzzy rules. The dual purpose of the proposed modelling approach is not only to classify beef samples in the relevant quality class (i.e. fresh, semi-fresh and spoiled), but also to predict their associated microbiological population. Comparison results against advanced machine learning schemes indicated that the proposed modelling scheme could be considered as a valuable detection methodology in food microbiology

A unifying hypothesis for PNMZL and PTFL: morphological variants with a common molecular profile

Pediatric nodal marginal zone lymphoma (PNMZL) is an uncommon B-cell neoplasm affecting mainly male children and young adults. This indolent lymphoma has distinct characteristics that differ from those of conventional nodal marginal zone lymphoma (NMZL). Clinically, it exhibits overlapping features with pediatric-type follicular lymphoma (PTFL). To explore the differences between PNMZL and adult NMZL and its relationship to PTFL, a series of 45 PNMZL cases were characterized morphologically and genetically by using an integrated approach; this approach included whole-exome sequencing in a subset of cases, targeted next-generation sequencing, and copy number and DNA methylation arrays. Fourteen cases (31%) were diagnosed as PNMZL, and 31 cases (69%) showed overlapping histologic features between PNMZL and PTFL, including a minor component of residual serpiginous germinal centers reminiscent of PTFL and a dominant interfollicular B-cell component characteristic of PNMZL. All cases displayed low genomic complexity (1.2 alterations per case) with recurrent 1p36/TNFRSF14 copy number-neutral loss of heterozygosity alterations and copy number loss (11%). Similar to PTFL, the most frequently mutated genes in PNMZL were MAP2K1 (42%), TNFRSF14 (36%), and IRF8 (34%). DNA methylation analysis revealed no major differences between PTFL and PNMZL. Genetic alterations typically seen in conventional NMZL were absent in PNMZL. In summary, overlapping clinical, morphologic, and molecular findings (including low genetic complexity; recurrent alterations in MAP2K1, TNFRSF14, and IRF8; and similar methylation profiles) indicate that PNMZL and PTFL are likely part of a single disease with variation in the histologic spectrum. The term "pediatric-type follicular lymphoma with and without marginal zone differentiation" is suggested.Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved