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  • 11
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: This study evaluates potential regulating factors in primary pulmonary carcinoid tumours, 16 typical and four atypical samples, with special emphasis on apoptosis and the bcl-2 gene family. Furthermore, p53-related oncogenes were analysed in a search for associated biological parameters.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsThe in-situ end-labelling technique (ISEL) was used to determine apoptotic cells, in addition to immunohistochemical methods, which were used to investigate the expression of the Ki67 antigen (avidin–biotin complex (ABC) method) and bcl-2, bcl-x, p53, p21/waf1, p27 and mdm-2 proteins (catalysed reporter deposition (CARD) technique). The incidence of apoptotic tumour cells was significantly enhanced in typical carcinoids. The bcl-2 protein was expressed to a higher degree in atypical carcinoids, which displayed a higher proliferative capacity as well. In contrast, bcl-x was observed predominantly in so-called typical carcinoids. The tumour cell turnover index was the most distinguishing parameter between both entities. All carcinoid tumours failed to show a staining for p53, p21/waf, p27 and mdm-2 proteins.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionsThe different biological behaviour of the carcinoid tumours under study seems to be influenced by the bcl-2 gene family preventing programmed cell death. We speculate that this results in a more aggressive course in atypical carcinoid tumours.
    Type of Medium: Electronic Resource
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  • 12
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: In addition to predominant granulocytic proliferation, bone marrow morphology in Philadelphia chromosome positive (Ph1+) CML is characterized by atypical dwarf or microforms of megakaryocytes. However, following therapy with interferon-α2b (IFN), these micromegakaryocytes occur less frequently. The purpose of this study was to elucidate whether the reappearance of normal megakaryocytes may be associated also with a reduction of the bcr/abl-positive cell clone.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and results:Fluorescence in-situ hybridization (FISH) technique in combination with immunomorphometry (CD61) was performed on trephine biopsies. A total of 311 CD61-positive megakaryocytes, including precursors and atypical microforms, were evaluated in pre-treatment specimens derived from 11 patients with Ph1+ CML. A specific fusion site marking the bcr/abl translocation was found in 87% of megakaryocytes which showed a size of 169 ± 35 μm2. In untreated patients, atypical microforms (size 200 μm2) were observed in 66% of the total megakaryocytic population. Following IFN therapy 369 megakaryocytes could be analysed in sequential examinations and were found to display a significant decrease (63%) in positive fusion signals. In addition there was also a significant enhancement in average size (252 ± 66 μm2) reflecting a reduction in the number of micromegakaryocytes (43%). These findings were particularly conspicuous in three patients with a major to complete cytogenetic remission.〈section xml:id="abs1-3"〉〈title type="main"〉Conclusions:A normalization of megakaryocyte size following IFN therapy in CML is significantly associated with a loss of the bcr/abl translocation site and therefore indicates a (partial) recovery of normal haematopoiesis.
    Type of Medium: Electronic Resource
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  • 13
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewisa and sialyl-Lewisx antigens in colorectal adenocarcinoma Aims: The significance of MUC1, MUC2 and sialylated Lewis blood group antigens as prognostic markers in colorectal adenocarcinoma was investigated in a large series of patients because previous investigations revealed inconsistent results due to unrelated tumour samples from different patient groups and methodological differences. Methods and results: Tissues from 243 patients with colorectal adenocarcinoma were stained immunohistochemically. MUC1 showed a strong immunoreactivity (in more than 35% of the tumour area) in 32.5%, MUC2 in 51.0%, sialyl-Lewisx in 67.9% and sialyl-Lewisa in 73.7% of the cases, respectively. MUC1 immunoreactivity displayed a significant correlation with tumour progression as reflected by advancing pTNM staging and poor differentiation. MUC2 expression was significantly stronger in mucinous adenocarcinomas. Sialyl-Lewisx immunostaining correlated with the extent of lymph node metastasis as well as low cytological differentiation. According to univariate and multivariate analysis (P 〈 0.0001) only MUC1 reactivity represented a marker of worse survival probability, opposed to the sialylated Lewis antigens that did not exert a predictive value. Conclusions: According to our data, MUC1 and sialyl-Lewisx immunoreactivity exhibit statistically significant correlations with established markers of tumour progression. However, only MUC1 presents as an independent prognostic factor of colorectal adenocarcinoma.
    Type of Medium: Electronic Resource
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  • 14
    Electronic Resource
    Electronic Resource
    Oxford, UK : Blackwell Science Ltd
    Histopathology 37 (2000), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: AimsBone marrow histopathology reveals a striking heterogeneity at diagnosis of Philadelphia chromosome positive (Ph1+) chronic myelogenous leukaemia (CML). Based on semiquantitative evaluations of the number of megakaryocytes and the content of fibres, various histological subtypes have been postulated. However, little information exists on whether these groups represent stable categories of the different classification systems and whether therapeutic regimes exert any influence on the putative shift of histological patterns.Methods and resultsA retrospective clinicopathological study was performed on 396 bone marrow biopsies derived from 173 patients. There were at least two representative trephines taken at diagnosis and at median intervals of 16 months. Processing of the specimens involved immunostaining with CD61 (megakaryopoiesis) and Ret40f (erythropoiesis) and Gomori's silver impregnation technique. Based on morphometric analysis and in accordance with the general appearance of bone marrow histology three different histological subtypes were distinguished. These consisted of a granulocytic (51 patients), a predominantly megakaryocytic (73 patients) and a myelofibrotic pattern (49 patients). Follow-up biopsies revealed that a significant transition of histological groups occurred and that, independently of treatment modalities, the myelofibrotic category was associated with an unfavourable prognosis. Of the 124 patients without myelofibrosis at onset, 42% later transformed into the myelofibrotic subtype. However, these patients showed no prevalence of either a pre-existing granulocytic or megakaryocytic growth. Myelofibrotic changes were significantly associated with interferon (IFN) and busulfan (BU) therapy. On the other hand, a transition of a myelofibrotic into a nonfibrotic subtype was detectable in 17 of the 49 patients under study and related to hydroxyurea (HU) treatment.ConclusionsHistological classification systems of bone marrow features in CML do not represent stable patterns, but may be significantly altered by therapy, in particular IFN and HU.
    Type of Medium: Electronic Resource
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  • 15
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Myelodysplastic syndromes, AIDS-related myelopathy and non-specific inflammatory reactions (mostly rheumatoid myelitis) are characterized by normo- to hypercellular bone marrow, but frequently display cytopenias in the peripheral blood. In the current study we have addressed the question whether this situation reflects an increased programmed cell death in haemopoiesis. For this purpose, the in situ end-labelling technique was applied to formalin-fixed and paraffin-embedded trephine biopsies derived from patients and a control group without any haematological disorder. Results were evaluated by morphometry. Significantly more apoptotic cell death was observed in the haemopoietic marrow of patients with either disease. Using double-immunohistochemistry with the monoclonal antibody PG-M1 (CD68), we were able to demonstrate that approximately one third of the apoptotic cells were ingested by macrophages. Our findings are in keeping with previously published data that postulated increased frequencies of macrophages in these disorders as well as raised serum levels of TNF-α.
    Type of Medium: Electronic Resource
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  • 16
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Expression of MMP-2 is associated with progression and lymph node metastasis of gastric carcinoma Aims: One important step in tumour invasion is the penetration of the basement membrane. Matrix metalloproteinases (MMPs) play a key role in the migration of normal and malignant cells through the basement membrane. The aim of this study was to investigate correlations between matrix metalloproteinase 2 (MMP-2) immunoreactivity and currently used classification systems and possible relationships between lymph node metastasis and MMP-2 expression. Methods and results: This prospective study analysed specimens obtained from 114 gastric cancer patients (mean age 64 years; range 33–86 years) who underwent gastrectomy with extended lymphadenectomy. All specimens were categorized according to UICC classification, WHO classification, tumour differentiation, Laurén classification, Ming classification and Goseki classification. Formalin-fixed paraffin-embedded tumour specimens were stained using an avidin–biotin complex peroxidase assay. MMP-2 expression in the tumour epithelium was studied by immunohistochemistry with semiquantitative (score 0–3) evaluation. The MMP-2 staining pattern was positive (score 1–3) in 93 (81.6%) specimens and negative (score 0) in 21 (18.4%) samples. No significant correlations were found between MMP-2 expression and other variables such as age, tumour differentiation, WHO, Lauren, Goseki, and Ming classifications. In contrast, the intensity of MMP-2 staining in tumour cells correlated significantly with depth of tumour infiltration (T-stage), lymph node metastasis (N-stage), distant metastasis (M-stage), and UICC stage. Conclusions: Expression of MMP-2 is strongly associated with tumour progression and lymph node metastasis in gastric cancer. Therefore MMP-2 staining may be clinically useful as predictor of tumour progression, especially for lymph node metastasis.
    Type of Medium: Electronic Resource
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  • 17
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    Unknown
    Berlin : Periodicals Archive Online (PAO)
    Kant-Studien. 58:3 (1967) 285 
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  • 18
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochimica et Biophysica Acta (BBA)/Biomembranes 769 (1984), S. 253-260 
    ISSN: 0005-2736
    Keywords: (Paramecium) ; Ca^2^+ transport ; Ciliary membrane ; Fluorescence anisotropy ; Membrane fluidity ; Temperature dependence
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Medicine , Physics
    Type of Medium: Electronic Resource
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  • 19
    ISSN: 0022-5320
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology
    Type of Medium: Electronic Resource
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  • 20
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Biochemical and Biophysical Research Communications 124 (1984), S. 178-182 
    ISSN: 0006-291X
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Biology , Chemistry and Pharmacology , Physics
    Type of Medium: Electronic Resource
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