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  • 1
    Electronic Resource
    Electronic Resource
    Npm/alk fusion mRNA expression in Hodgkin and Reed–Sternberg cells is rare but does occur: Results from single-cell cDNA analysis (1997)
    Springer
    Annals of oncology 8 (1997), S. 83-87 
    Details
    ISSN: 1569-8041
    Keywords: clonal heterogeneity ; Hodgkin's disease ; NPM/ALK ; single cell PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The translocation t(2;5)(p23;q35) leads to the fusion of thenucleophosmin gene (NPM) on chromosome 5q35 to the recently describedreceptor kinase ALK 2p23. It is characteristic of a subgroup of CD30+large-cell anaplastic non-Hodgkin's lymphoma (ALCL). Since some cases ofHodgkin's disease (HD) and ALCL share common features, a common pathogenesishas been proposed in a report of the expression of NPM/ALK fusion mRNA in11/13 Hodgkin's lymphomas. Patients and methods: We approached this question by micromanipulatoryisolation of single Hodgkin and Reed–Sternberg (H-RS) cells andsubsequent RT-PCR amplification of NPM/ALK fusion cDNA from these singlecells. Results: Specificity of cell selection was shown by the HD-specificpattern of EBV-gene expression in single H-RS cells. In 4 out of 7 cases,NPM/ALK fusion cDNA was detected in the RNA from whole lymph node tissue. In2 out of 9 cases, NPM/ALK fusion sequences were amplified from single H-RScells, albeit in a very low frequency (〈5%). Conclusions: These data indicate that NPM/ALK fusion transcripts donot play an early role in the pathogenesis of HD. Whether the rare expressionof NPM/ALK is the result of clonal heterogeneity or an indication for clonalevolution and progression toward ALCL can only be answered by the repeatedanalysis of indicator cases during the course of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008246719680
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    Paper (German National Licenses)
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  • 2
    Electronic Resource
    Electronic Resource
    Analysis of VH gene rearrangements from synovial B cells of patients with rheumatoid arthritis reveals infiltration of the synovial membrane by memory B cells (1997)
    Springer
    Rheumatology international 17 (1997), S. 145-150 
    Details
    ISSN: 1437-160X
    Keywords: Key words VH gene repertoire ; Immunoglobulin gene rearrangements ; Rheumatoid arthritis ; Somatic mutation ; Memory B cell
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The VH gene (Variable gene segments of the heavy chain locus) repertoire can be investigated by DNA analysis of rearranged immunoglobulin VH genes, which also allows for an indirect estimation of antibody selection by analysis of somatic mutations. Using a polymerase chain reaction (PCR) it is also possible to analyse these genes in small numbers of cells or even single cells. This approach was chosen to investigate germinal centre like lymphocyte follicles in the synovial membranes of two patients with rheumatoid arthritis (RA) in order to analyse the local humoral immune response in RA. Individual B-cell aggregates of synovial membrane of two patients with RA were isolated by micromanipulation from microscopic slides. VH-DH-JH (variable, diversity, and joining segments of the heavy chain locus) rearrangements in all possible VH-JH combinations were amplified from these B cell foci, cloned and subjected to sequence analysis. Sequence analysis revealed that most of the rearranged VH genes were somatically mutated with at least 1% (range 1.3 – 14.9%) somatic mutations and therefore were derived from antigen-selected memory B cells. Intraclonal diversity in one-third of the clones indicated the generation of memory B cells in the synovial membrane and characterized the synovial membrane as lymphatic tissue where secondary immune responses to an as yet unknown antigen take place.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s002960050026
    Library Location Call Number Volume/Issue/Year Availability
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    Paper (German National Licenses)
    Fulltext
  • 3
    Electronic Resource
    Electronic Resource
    Npm/alk fusion mRNA expression in Hodgkin and Reed–Sternberg cells is rare but does occur: Results from single-cell cDNA analysis (1997)
    Springer
    Annals of oncology 8 (1997), S. 83-87 
    Details
    ISSN: 1569-8041
    Keywords: clonal heterogeneity ; Hodgkin's disease ; NPM/ALK ; single cell PCR
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: The translocation t(2;5)(p23;q35) leads to the fusion of the nucleophosmin gene (NPM) on chromosome 5q35 to the recently described receptor kinase ALK 2p23. It is characteristic of a subgroup of CD30+large-cell anaplastic non-Hodgkin's lymphoma (ALCL). Since some cases of Hodgkin's disease (HD) and ALCL share common features, a common pathogenesis has been proposed in a report of the expression of NPM/ALK fusion mRNA in11/13 Hodgkin's lymphomas. Patients and methods: We approached this question by micro manipulatory isolation of single Hodgkin and Reed–Sternberg (H-RS) cells and subsequent RT-PCR amplification of NPM/ALK fusion cDNA from these single cells. Results: Specificity of cell selection was shown by the HD-specific pattern of EBV-gene expression in single H-RS cells. In 4 out of 7 cases, NPM/ALK fusion cDNA was detected in the RNA from whole lymph node tissue. In2 out of 9 cases, NPM/ALK fusion sequences were amplified from single H-RS cells, albeit in a very low frequency (〈5%). Conclusions: These data indicate that NPM/ALK fusion transcripts do not play an early role in the pathogenesis of HD. Whether the rare expression of NPM/ALK is the result of clonal heterogeneity or an indication for clonal evolution and progression toward ALCL can only be answered by the repeated analysis of indicator cases during the course of the disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008246719680
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
    Paper (German National Licenses)
    Fulltext
  • 4
    Electronic Resource
    Electronic Resource
    Behandlungsstrategien bei aggressiven Lymphomen (1997)
    Springer
    Der Onkologe 3 (1997), S. 522-529 
    Details
    ISSN: 1433-0415
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Die aggressiven Lymphome zeigen im Gegensatz zu den indolenten Lymphomen einen rasch progredienten klinischen Verlauf und führen unbehandelt innerhalb weniger Wochen oder Monate zum Tode. Aufgrund ihres guten Ansprechens auf Chemotherapie können aber auch in fortgeschrittenen Stadien dauerhafte Remissionen erzielt werden [1]. Aus diesem Grund erfolgt die Behandlung aggressiver Lymphome grundsätzlich in kurativer Intention. Im Gegensatz zu den indolenten Lymphomen werden aggressive Lymphome häufig primär auch in niedrigen Stadien diagnostiziert, so daß eine kurative Strahlentherapie prinzipiell möglich ist, jedoch seit der Einführung effektiver Polychemotherapie-Schemata als alleinige Modalität nur noch in Ausnahmefällen durchgeführt wird. Die Einführung von Anthracyclinen in die Behandlung aggressiver Lymphome durch das 1976 beschriebene CHOP-Schema [2] hat es ermöglicht, daß fast 2/3 der Patienten initial eine Remission erreichen, langfristig geheilt werden kann bis jetzt jedoch nur 1/3 der Patienten. Die Intensivierung der Chemotherapie in den letzten 2 Jahrzehnten durch die Einführung sogenannter Zweit- und Drittgenerationsschemata hat nicht zu einer wesentlichen Verbesserung der Therapieergebnisse geführt [3]. Aus diesem Grunde konzentrieren sich die klinischen Anstrengungen derzeit auf eine Intensivierung der Therapie auf der Basis des derzeitigen „Goldstandards”, des CHOP-Regimes. Dieses wird bei Patienten mit niedrigem Risiko durch Intervallverkürzung unter Einsatz hämatopoetischer Wachstumsfaktoren ermöglicht, während bei jungen Patienten mit hohem Risiko Hochdosistherapieverfahren mit Stammzellersatz überprüft werden. Ältere Patienten machen die Mehrzahl der Patienten mit aggressiven Lymphomen aus, weswegen die Etablierung kurativer Therapiestrategien mit akzeptabler Toxizität für diese Patientengruppe vordringlich ist. In dieser Arbeit werden die konventionellen Therapiestrategien besprochen, während die Hochdosisverfahren in der Arbeit von R. Haas dargestellt werden.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s007610050150
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    Paper (German National Licenses)
    Fulltext
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