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  • 38 000 Mr autoantigen  (1)
  • Bone marrow  (1)
  • Chronic myelogenous leukaemia  (1)
  • 1
    ISSN: 1432-2307
    Schlagwort(e): Chronic myelogenous leukaemia ; Philadelphia chromosome ; FISH ; Megakaryocyte
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Histological examination of bone marrow biopsies shows that about one-third of chronic myeloid leukaemia (CML) patients exhibit an increase of megakaryocytes. The megakaryocytic predominance may be so striking that differentiation from other chronic myeloproliferative disorders (CMPD) may be difficult in some CML patients. Megakaryocytes in CML are clonal as demonstrated by loss of glucose-6-phosphate dehydrogenase isoenzymes. The Ph translocation, fusing the abl and bcr genes on chromosomes 9 and 22, however, obviously occurs as a second step in tumour development. So far, the Ph translocation has not been assigned explicitly to megakaryocytes. The question is whether the megakaryocytic cell lineage could harbour the bcr/abl fusion in those CML cases with striking proliferation of megakaryocytes but lack this genetic defect in cases with normal or decreased megakaryocyte counts. We therefore performed triple-colour fluorescence in situ hybridization (FISH) for portions of the bcr and abl genes flanking the breakpoint in CML in paraffin sections of CML cases with normal and with increased numbers of megakaryocytes. This method allows identification of the bcr/abl fusion in single, morphologically intact cells, whereas conventional cytogenetics requires lysis and thus destruction of the cell. Among the 21 CML patients examined by FISH, 10 were informative for bcr and abl genes and displayed distinct hybridization signals within nuclei of bone marrow cells. Besides the granulopoietic cells, megakaryocytes of all those patients (4 without and 6 with varying grades of megakaryocytic increase) displayed bcr/abl fusion signals indiciative of a Ph translocation. The lack of hybridization signals in the remaining 11 cases indicates that this technique is not of value diagnostically and should be reserved for scientific questions. Positive controls consisted of conventional chromosome preparations from bone marrow aspirates demonstrating the Ph chromosome in all patients examined, and negative controls of paraffin sections of bone marrow biopsies from non-CML patients. These showed no fusion signals in bone marrow cells, including megakaryocytes, using FISH. Our results demonstrate clearly that not only the transforming event but also the Ph translocation leading to the bcr/abl fusion happens prior to the differentiation of the pluripotent stem cell into different myeloid lineages. The megakaryocytic proliferation evident in some CML cases is probably a consequence of the disease progress.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 2
    ISSN: 1432-1963
    Schlagwort(e): Schlüsselwörter Myelodysplastisches Syndrom ; Knochenmark ; Zytogenetik ; Histopathologie ; Prognose ; Key words Myelodysplastic syndrome ; Bone marrow ; Cytogenetics ; Histopathology ; Prognosis
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Beschreibung / Inhaltsverzeichnis: Summary The value of cytogenetics performed simultaneously with histopathology was evaluated in patients with myelodysplastic syndrome (MDS). Clonal karyotype changes of the bone marrow cells supporting the histological diagnosis were found in 38/69 cases (55 %). The chromosome aberrations, especially complex changes, were significantly correlated to distinct histopathological findings such as atypias of the haematopoietic cell lines and myelosclerosis. Complex karyotype changes were further associated with short survival of the MDS patients. Our results demonstrate that cytogenetic analyses are helpful in supplementing the histopathological diagnoses. Recent developments in molecular cytogenetics even allow the detection of chromosomal aberrations in non-dividing cells from cytological preparations or tissue sections which may become available for routine diagnosis.
    Notizen: Zusammenfassung Die Bedeutung simultaner zytogenetischer und histologischer Untersuchungen wurde bei Patienten mit myelodysplastischem Syndrom (MDS) überprüft. Die Ergebnisse zeigen, daß klonale Karyotypveränderungen der Knochenmarkzellen bei 38 der 69 (55 %) analysierten Patienten auftraten und damit häufig eine Absicherung der histologischen Diagnose erlaubten. Die Chromosomenanomalien, insbesondere komplexe Karyotypveränderungen, korrelierten signifikant mit einer Reihe histopathologischer Befunde, darunter Atypien der einzelnen hämatologischen Zellreihen und Myelosklerose. Durch den Nachweis komplexer Karyotypveränderungen war eine unabhängige prognostische Aussage möglich. Damit zeigen unsere Ergebnisse am Beispiel des MDS, daß zytogenetische Analysen eine sinnvolle Ergänzung der histologischen Untersuchung sein können. Darüber hinaus ist durch den Einsatz der molekularen Zytogenetik die Bestimmung von Chromosomenanomalien in zytologischen Ausstrichpräparaten oder Gewebeschnitten möglich, wodurch sich solche Befunde auch für die tägliche Diagnostik verwenden lassen.
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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  • 3
    ISSN: 1432-0428
    Schlagwort(e): Keywords Type I diabetes ; immunology ; autoantibodies ; target autoantigen ; 38 000 Mr autoantigen ; glima 38 ; proteolytic cleavage ; peptide mapping ; lectin binding ; deglycation.
    Quelle: Springer Online Journal Archives 1860-2000
    Thema: Medizin
    Notizen: Abstract Aims/hypothesis. Glima 38 is an N-glycated neuroendocrine membrane protein of Mr 38 000, which is recognised by autoantibodies in approximately 20 % of patients with Type I (insulin-dependent) diabetes mellitus. The aim of this study was to characterise the carbohydrate moiety and generate peptide maps of glima 38. Methods. Sera of high immunoreactivity to glima 38 were used to isolate 35-S methionine-labelled protein from βTC-3 cells and a neuronal cell line GT1.7. Tunicamycin was used to inhibit N-glycation of glima 38 and define the core protein. The carbohydrate moiety was characterised for tunicamycin sensitivity, lectin binding and susceptibility to different endoglycosidases. The protein moiety was subjected to digestion by proteases to define peptide maps. Results. The autoreactive epitopes in glima 38 recognised by Type I diabetic sera are conformational and independent of the carbohydrate moiety. Inhibition of N-glycation of glima 38 in vivo, shows a protein core of Mr 22 000 in both pancreatic β-(βTC3) and neuronal (GT1.7) cell lines. The carbohydrate moieties in the two cell types are distinct but contain a similar amount of terminal sialic acid residues and at least five oligosaccharide chains Glima 38 binds Triticum vulgare and Ricinus communis I lectins. Endoproteinase treatment of the Mr 22 000 core protein results in peptides of Mr 4500 and Mr 20 000 with Lys-C, and peptides of Mr 4 000 and Mr 11 000–12 000 with Glu-C/V8 and Asp-N proteases. Conclusion/interpretation. The biochemical properties of glima 38 define it as a new autoantigen in Type I diabetes and provide a basis for its purification. [Diabetologia (2000) 43: 598–608]
    Materialart: Digitale Medien
    Bibliothek Standort Signatur Band/Heft/Jahr Verfügbarkeit
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