Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis

The pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant nonneoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected L&H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&H cells to and/or that they originate from germinal center B cells at the transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell–rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive nuclear factor {kappa}B activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies

Rare Occurrence of Classical Hodgkin's Disease as a T Cell Lymphoma

Recent work identified Hodgkin and Reed-Sternberg (H/RS) cells in classical Hodgkin's disease (cHD) as clonal progeny of mature B cells. Therefore, it is generally assumed that cHD homogenously represents a B cell lymphoma. In a subset of cHD, however, H/RS cells expressing T cell–associated proteins may be candidates for alternative lineage derivation. Single H/RS cells with cytotoxic T cell phenotype were micromanipulated from three cases of cHD and analyzed by single cell polymerase chain reaction for immunoglobulin heavy (IgH) and light chain (IgL) gene rearrangements, T cell receptor (TCR)-β gene rearrangements, and germline configuration of the IgH and TCR-β loci. H/RS cells from two cases of cHD harbored clonal, somatically mutated Ig gene rearrangements, whereas TCR-β loci were in germline configuration. In contrast, H/RS cells from an additional case harbored clonal TCR-β variable/diversity/joining (VDJ) and DJ gene rearrangements, whereas the IgH locus was in germline configuration on both alleles. Thus, in two cases of cHD with H/RS cells expressing cytotoxic T cell molecules, the tumor cells are derived from mature B cells that aberrantly express T cell markers. In a third case, however, H/RS cells were derived from a T cell, demonstrating that cHD can also occur as a T cell lymphoma

Origin and pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma as revealed by global gene expression analysis

The pathogenesis of nodular lymphocyte–predominant Hodgkin lymphoma (NLPHL) and its relationship to other lymphomas are largely unknown. This is partly because of the technical challenge of analyzing its rare neoplastic lymphocytic and histiocytic (L&H) cells, which are dispersed in an abundant nonneoplastic cellular microenvironment. We performed a genome-wide expression study of microdissected L&H lymphoma cells in comparison to normal and other malignant B cells that indicated a relationship of L&H cells to and/or that they originate from germinal center B cells at the transition to memory B cells. L&H cells show a surprisingly high similarity to the tumor cells of T cell–rich B cell lymphoma and classical Hodgkin lymphoma, a partial loss of their B cell phenotype, and deregulation of many apoptosis regulators and putative oncogenes. Importantly, L&H cells are characterized by constitutive nuclear factor κB activity and aberrant extracellular signal-regulated kinase signaling. Thus, these findings shed new light on the nature of L&H cells, reveal several novel pathogenetic mechanisms in NLPHL, and may help in differential diagnosis and lead to novel therapeutic strategies

Familienwissenschaftliche Rhetorik : eine explorative Analyse ausgewählter Texte

In contemporary societies we can observe an increasing interest for the forms of persuasive public communication, for which the term "new rhetoric" has been proposed recently. It includes the analysis of scholarly publications. And, in this way, is related to developments in epistemology and in the sociology of science. Family research is a fruitful field for research on this kind of scientific rhetoric. A small number of key-terms, among them prominently the "pluralization of family forms", play a dominant role in the literature dealing with recent changes of the family. At the same time, a remarkable rise of family research led to a "pluralization of theoretical approaches". Also, speaking and writing on the family unavoidably contains moral, and therefore rhetorical connotations, due to the anthropological dimensions of the topic. The paper, which informs about "work in progress", begins with an overview of the theoretical foundations of scientific rhetoric, and of a model concerning the attention paid in public discourses to sociological propositions of the family. It is followed by a detailled comparative analysis of three recent articles on the situation of the family and related forms of private life in Germany. Finally, a frame of reference for the analysis of family rhetoric in scholarly texts is sketched out

"Krieg zwischen den Generationen?" : die Darstellung von Generationenbeziehungen in ausgewählten Sachbuchtexten

The "war between the generations" is becoming a common topic of public discourse. What arguments and rhetorical elements are used to characterize intergenerational relations? How does this relate to recent findings in the social sciences? Three popular non-fiction books were chosen for a detailed analysis of arguments and rhetorical elements in the public discourse about generations. This special genre is becoming even more important in a time, when more and more people are looking for knowledge with which to orient themselves in life. They have more education and interest in discussing major contemporary issues. Another important reason for the choice of topics is the self-referentiality of the media. This means that certain topoi found in non-fiction books are used in other types of publication.After describing our analytical method, we introduce the content of the three books. We then reconstruct important topoi, typical arguments and rhetorical elements of each text. Through a comparison we gain insights about different perspectives on intergenerational relations and propose tentative explanations for their emergence. Finally, we summarize the main elements of the texts and discuss possible functions of the found dramatization. This leads to questions of whether and how non-fiction books and texts in the social sciences can influence each other

Lipidome of midbody released from neural stem and progenitor cells during mammalian cortical neurogenesis

Midbody release from proliferative neural progenitor cells is tightly associated with the neuronal commitment of neural progenitor cells during the progression of neurogenesis in the mammalian cerebral cortex. While the central portion of the midbody, a cytoplasmic bridge between nascent daughter cells, is engulfed by one of the daughter cell by most cells in vitro, it is shown to be released into the extracellular cerebrospinal fluid in vivo in mouse embryos. Several proteins have been involved in midbody release; however, few studies have addressed the participation of the plasma membrane’s lipids in this process. Here, we show by Shotgun Lipidomic analysis that phosphatydylserine (PS), among other lipids, is enriched in the released midbodies compared to lipoparticles and cellular membranes, both collected from the cerebrospinal fluid of the developing mouse embryos. Moreover, the developing mouse embryo neural progenitor cells released two distinct types of midbodies carrying either internalized PS or externalized PS on their membrane. This strongly suggests that phagocytosis and an alternative fate of released midbodies exists. HeLa cells, which are known to mainly engulf the midbody show almost no PS exposure, if any, on the outer leaflet of the midbody membrane. These results point towards that PS exposure might be involved in the selection of recipients of released midbodies, either to be engulfed by daughter cells or phagocytosed by non-daughter cells or another cell type in the developing cerebral cortex