3,270 research outputs found
FOR 1961: Reife T-Zell-Lymphome Mechanismen der gestörten, klonalen T-Zell-Homöostase
Die dankenswerterweise von der Deutschen Forschungsgemeinschaft geförderte Forschergruppe hat ihre Ziele weitgehend erreicht und ist insgesamt als sehr erfolgreich einzustufen. Die Projektgruppen hatten das Ziel, polyklonale und klonale T-Zellentwicklungen unter verschiedenen Aspekten, wie Zellhierarchien, klonale Kontrolle und T-Zell-Lymphomentstehung, zu untersuchen. Neben zahlreichen molekularen Methoden kamen auch bioinformatische Ansätze zum Einsatz, die zu einem besseren biologischen Verständnis der T-Zellentwicklung im humanen wie auch im murinen System geführt haben. Zusätzlich zu den primär definierten Zielen entstand durch die Kooperation mehrere Gruppen eine neue Technologie, die es gestattet Vorgänge in Histologischen Schnitten des Immunsystems in 3D und 4D also in Raum und Zeit zu analysieren. Insbesondere auch diese Ergebnisse waren Ausgangspunkt für ein DFG-Folgeprojekt mit dem Inhalt der Erforschung von T-Zell- und NKZelltherapien („Etablierung eines 4D ex vivo Netzwerk-Modells humaner Lymphome zur Evaluation der Wirksamkeit von CAR T- und NK-Zell-Therapien“ (4D-CARLY)). Desweiteren beflügelte und ermöglichte die Forschungsguppe ein durch das BMBF gefördertes maschinelles Lernprogramm im Immunsystem („Patho 234: Multidimensionale Bildanalyse von reaktiven und neoplastischen Lymphknoten durch Maschinelles Lernen“). Die Forschergruppe war zudem Ausgangspunkt für zahlreiche Promotionsarbeiten. Besonders hervorzuheben ist, dass eine Wissenschaftlerin aus der Forschergruppe (Sylvia Hartmann) den Ruf auf eine W3-Professur (Ordinariat für Pathologie an der Universität Essen) erhalten hat. Weiterhin besetzte ein weiteres Mitglied der Forschergruppe Herr Marco Herling eine W2-Professur an der Universität Leipzig. Auch der Sprecher der Forschergruppe MartinLeo Hansmann erhielt einen Ruf auf eine Universitätsprofessor für Hämatopathologie an der Universität Innsbruck (Ruf wurde abgelehnt) und eine Distinguished Professorship an der Universität Frankfurt. Der Erfolg der Forschergruppe spiegelt sich in zahlreichen Publikationen wieder und durch die aufgeführten Folgeprojekte wurden wesentliche Aspekte des Gesamtkonzeptes des durch die DFG geförderten Vorhabens verstetigt
Intracellular signalling molecules as immunohistochemical markers of normal and neoplastic human leucocytes in routine biopsy samples.
We have investigated whether intracellular signal transduction molecules can be used as immunohistological markers of normal and neoplastic human leucocytes in routine tissue sections. We obtained selective labelling of white cells for eight such molecules (the 'linker' molecules SLP-76 and BLNK, the Src family kinases Lyn, Fyn, Syk and Hck, and the phospholipases PLC-gamma1 and PLC-gamma2). Antibodies to SLP-76 and PLC-gamma1 selectively labelled T cells, and antibodies to BLNK, Lyn, Fyn, Syk and PLC-gamma2 labelled B cells (although Fyn immunostaining was restricted to mantle zone B cells). Antibodies to the Syk and Hck kinases labelled probable thymocyte precursors at the periphery of the thymic cortex. In addition to lymphoid cells, several other leucocyte types were immunostained (e.g. SLP-76, Lyn, Syk and Hck were found in megakaryocytes, myeloid cells and/or macrophages, and PLC-gamma2 was detected in arterial endothelium). SLP-76 and PLC-gamma1 were found in most T-cell lymphomas studied, and some B-cell lymphomas were also positive for PLC-gamma1 (e.g. diffuse large cell and Burkitt's lymphoma). The five B cell-associated markers were found in most B-cell non-Hodgkin's lymphomas, although some diffuse large B-cell lymphomas were negative (e.g. for Lyn) and anti-Fyn tended not to stain small B-cell neoplasms. The observation that a range of leucocyte signalling molecules can be detected in routine biopsies offers new possibilities for studying normal and neoplastic human white cells in diagnostic tissue samples
Measurement of the Bs0-Bs0 oscillation frequency δms in Bs0→Ds-(3)π decays
The Bs0-Bs0 oscillation frequency δms is measured with 36 pb-1 of data collected in pp collisions at s=7TeV by the LHCb experiment at the Large Hadron Collider. A total of 1381 Bs0→Ds-π+ and Bs0→Ds-π+π-π + signal decays are reconstructed, with average decay time resolutions of 44 fs and 36 fs, respectively. An oscillation signal with a statistical significance of 4.6σ is observed. The measured oscillation frequency is δm s=17.63±0.11(stat)±0.02(syst)ps -1
Peripheral T cell lymphomas with follicular T helper phenotype: a new basket or a distinct entity? Revising Karl Lennert's personal archive
AIMS:
To revise 25 cases selected from Karl Lennert's personal archive (21) and Bologna and Frankfurt Registries (four) because of cytological similarities.
METHODS AND RESULTS:
All cases were provided with paraffin blocks and studied by immunohistochemistry and molecular techniques. While phenotyping was very informative, among molecular studies only EBER in situ-hybridization (ISH) was successful. Twenty-two cases were concluded as peripheral T cell lymphomas (PTCL). Of these, six were reclassified as angioimmunoblastic T cell lymphoma (AITL), 13 as PTCL, not otherwise specified (NOS), including four follicular variants and one tumour with T-zone pattern, and three as borderline tumours between AITL and PTCL/NOS. All these cases consisted homogeneously of small/medium-sized elements with mild nuclear atypia and an evident rim of clear/pale cytoplasm. On immunohistochemistry, they regularly expressed three to six follicular helper T cell (FTH)-associated markers. EBER-ISH revealed scattered EBV-infected B cells in all tumours except those with 'follicular' growth pattern. The content of follicular dendritic cells and high-endothelial venules varied significantly depending on the histotype.
CONCLUSIONS:
This study shows that: (i) historical material can be still employed usefully, and (ii) the FTH-phenotype corresponds to a broad spectrum of PTCLs that might form a new category to be validated in future molecular and clinicopathological analyses
Clonal T-cell proliferations occasionally occur in Kikuchi–Fujimoto disease
Kikuchi-Fujimoto disease (KFD) is a benign self-limiting disorder that frequently leads to swelling of cervical lymph nodes in young women. It has a characteristic histologic appearance with sharply demarcated foci containing apoptotic debris, histiocytes, and proliferating large T-cells. Since in the past years, core needle biopsies have been increasingly used for diagnostic work-up, a small biopsy of the pathognomonic proliferating T-cell foci may lead to misinterpretation as a large T-cell neoplasia. The aim of the present study therefore was to analyze how frequently clonal T-cell receptor (TCR) amplificates may be obtained in KFD using a commonly used TCR gamma rearrangement clonality assay. In 88 KFD cases, TCR gamma clonality assays could be successfully applied. Clonal peaks of TCR gamma in front of a polyclonal background were observed in 15 cases (18%). The investigated clinical parameters (age, gender, extent of infiltration of the lymph node, percentage of proliferative compart-ment) did not differ between patients with detectable TCR gamma clones from those patients who had polyclonal TCR gamma results
PROPERTIES OF INTERFACES IN THE 2 AND 3-DIMENSIONAL ISING-MODEL
BERG BA, HANSMANN U, Neuhaus T. PROPERTIES OF INTERFACES IN THE 2 AND 3-DIMENSIONAL ISING-MODEL. ZEITSCHRIFT FUR PHYSIK B-CONDENSED MATTER. 1993;90(2):229-239.To investigate order-order interfaces, we perform multimagnetical Monte Carlo simulations of the 2D and 3D Ising model. Following Binder we extract the interfacial free energy from the infinite volume limit of the magnetic probability density. Stringent tests of the numerical methods are performed by reproducing with high precision exact 2D results. In the physically more interesting 3D case we estimate the amplitude F-0(S) of the critical interfacial tension F3 = F-0(S)t(mu) to be F-0(S) = 1.52 +/- 0.05. This result is in good agreement with a previous MC calculation by Mon, as well as with experimental results for related amplitude ratios. In addition, we study in some details the shape of the magnetic probability density for temperatures below the Curie point
CD30 expression in neoplastic T cells of follicular T cell lymphoma is a helpful diagnostic tool in the differential diagnosis of Hodgkin lymphoma
Follicular T cell lymphoma is derived from follicular T-helper cells. In many cases, neoplastic T cells form rosettes around Hodgkin–Reed–Sternberg-like cells, which can lead to the misdiagnosis of classical Hodgkin lymphoma. The aim of the present study was to obtain a better understanding of this rosetting phenomenon and to recognize features that are helpful in the differential diagnosis of classical Hodgkin lymphoma. Sixteen mostly elderly follicular T cell lymphoma patients (mean 66 years) were analyzed. Fifteen of the 16 follicular T cell lymphoma cases presented with Hodgkin–Reed–Sternberg-like cells, which were CD20-positive in 27% of the cases and Epstein–Barr virus-infected in nearly all cases. Frequently, the immunophenotype of rosetting neoplastic T cells differed from the bulk neoplastic cells with less numerous T-follicular helper cell markers expressed, suggesting a modulation of T-follicular helper cell marker expression in the neoplastic T cells. In 75% of the cases, variable CD30 expression was encountered in the neoplastic T cells, likely reflecting an activation state in these cells. Hodgkin–Reed–Sternberg-like cells were positive for CCL17, and follicular T cell lymphoma tumor cells expressed its receptor CCR4 at variable intensity, thus potentially explaining the phenomenon of the tumor cells’ rosetting around Hodgkin–Reed–Sternberg-like cells. In summary, this study confirms the presence of Hodgkin–Reed–Sternberg-like cells in a high number of cases of follicular T cell lymphoma, suggesting that Hodgkin–Reed–Sternberg-like cells may contribute to the development of this lymphoma. Hodgkin–Reed–Sternberg-like cells in follicular T cell lymphoma cannot reliably be differentiated from the Hodgkin–Reed–Sternberg cells of classical Hodgkin lymphoma based on their immunophenotype. In contrast, demonstration of a T-follicular helper cell phenotype with CD10 and frequent CD30 expression in the neoplastic T cell population can help to establish the diagnosis of follicular T cell lymphoma, and may even indicate CD30 as a therapeutic target for these patients
Langevin equations for the run-and-tumble of swimming bacteria
The run and tumble motions of a swimming bacterium are well characterized by two stochastic variables: the speed v(t) and the change of direction or deflection x(t) = cosφ(t), where φ(t) is the turning angle at time t. Recently, we have introduced [G. Fier, D. Hansmann and R. C. Buceta, A stochastic model for directional changes of swimming bacteria, Soft Matter, 2017, 13, 3385-3394.] a single stochastic model for the deflection x(t) of an E. coli bacterium performing both types of movement in isotropic media without taxis, based on available experimental data. In this work we introduce Langevin equations for the variables (v, x), which for particular values of a control parameter β correspond to run and tumble motions, respectively. These Langevin equations have analytical solutions, which make it possible to calculate the statistical properties of both movements in detail. Assuming that the stochastic processes x and v are not independent during the tumble, we show that there are small displacements of the center of mass along the normal direction to the axis of the bacterial body, a consequence of the flagellar unbundling during the run-to-tumble transition. Regarding the tumble we show, by means of the directional correlation, that the process is not stationary for tumble-times of the order of experimentally measured characteristic tumble-time. The mean square displacement is studied in detail for both movements even in the non-stationary regime. We determine the diffusion and ballistic coefficients for tumble- and run-times, establishing their properties and relationships.Fil: Fier, Guido. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Físicas de Mar del Plata. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Físicas de Mar del Plata; ArgentinaFil: Hansmann, David. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Físicas de Mar del Plata. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Físicas de Mar del Plata; ArgentinaFil: Buceta, Ruben Carlos. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Mar del Plata. Instituto de Investigaciones Físicas de Mar del Plata. Universidad Nacional de Mar del Plata. Facultad de Ciencias Exactas y Naturales. Instituto de Investigaciones Físicas de Mar del Plata; Argentin
Expression of intracellular signaling molecules in classical and lymphocyte predominance Hodgkin disease.
The neoplastic cells in classical Hodgkin disease (Reed-Sternberg cells) are of B-lymphoid origin, but they lack many markers of this cell lineage, for example, immunoglobulin, CD20, and B-cell-associated transcription factors. In contrast, the neoplastic cells ("L&H" cells) in lymphocyte predominance Hodgkin disease retain the molecular profile of germinal center B cells. In this paper, we investigated the expression in Hodgkin disease (45 cases and 3 cell lines) of 5 intracellular signaling molecules found in B cells. The Src family kinase Syk, the B-cell adaptor protein BLNK, and phospholipase C (PLC)-gamma2 were consistently absent from Reed-Sternberg cells, whereas 2 other Src kinases (Lyn and Fyn) were heterogeneously expressed in a proportion of cases (12% and 42%, respectively). In contrast, the tumor cells in all cases of lymphocyte predominance Hodgkin disease were positive for Fyn, Syk, BLNK, and PLC-gamma2, and Lyn immunostaining was seen in a minority of biopsies. These results indicate that in Reed-Sternberg cells, the defect in B-cell lineage marker expression includes a spectrum of molecules involved in intracellular signaling, a finding in keeping with recent gene expression profiling studies. Furthermore, the clear difference in expression of signaling proteins between the 2 major subtypes of Hodgkin disease may be of diagnostic value
SIMULATION OF AN ENSEMBLE WITH VARYING MAGNETIC-FIELD - A NUMERICAL DETERMINATION OF THE ORDER-ORDER INTERFACE TENSION IN THE D=2 ISING-MODEL
BERG BA, HANSMANN U, Neuhaus T. SIMULATION OF AN ENSEMBLE WITH VARYING MAGNETIC-FIELD - A NUMERICAL DETERMINATION OF THE ORDER-ORDER INTERFACE TENSION IN THE D=2 ISING-MODEL. PHYSICAL REVIEW B. 1993;47(1):497-500.In analogy with a recently proposed multicanonical ensemble we introduce an ensemble where the partition function is simulated with a term in the action containing a varying magnetic field. Using this ensemble we demonstrate on lattices with periodic boundary conditions that it is possible to enhance the appearance of order-order interfaces by many orders of magnitude. To perform a stringent test of the method we consider the D = 2 Ising model at beta = 0.5 and simulate square lattices up to size 100 x 100. By a finite-size scaling analysis, the order-order interface tension per unit area is obtained. Our best infinite-volume extrapolation is in excellent agreement with Onsager's exact result
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