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  • Electronic Resource  (13)
  • 2005-2009  (2)
  • 1995-1999  (11)
  • 1
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims : Extrafollicular activation of B cells is rarely observed in human lymph nodes. The aim of this study was to extensively analyse the expression of surface molecules and transcription factors in four such cases, comparing them with follicular B cells and medullary cord plasma cells.Methods and results : Various combinations of B-cell-related surface markers and transcription factors were studied by triple immunofluorescence. While in the germinal centre, reactive immunoglobulin production occurred exclusively in non-proliferating cells, in extrafollicular activation proliferation of B cells and immunoglobulin production coexisted. In two of these cases proliferating cells were mainly IgG+CD27+, i.e. derived from class-switched postgerminal centre memory B cells. Some of these cells expressed CD30. In the other two cases, immunoglobulin-forming cells were non-class-switched IgM+CD27– B cells, representing a primary expansion of naive B cells.Conclusions : Extrafollicular B-cell activation is the morphological correlate of rapid B-cell responses that do not involve the germinal centres. It is pathogenetically heterogeneous, comprising primary responses that occur prior to, or independent of, germinal centre reaction or memory cell activation in recall responses.
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  • 2
    Electronic Resource
    Electronic Resource
    Oxford, U.K. and Cambridge, USA : Blackwell Science Ltd
    Histopathology 35 (1999), S. 0 
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Five cases of a characteristic low-grade thymic epithelial tumour are described that we suggest calling metaplastic carcinoma of the thymus.〈section xml:id="abs1-2"〉〈title type="main"〉Methods and resultsThe patients' ages ranged from 44 to 71 (mean 56.2) years. Four of the patients were male. Three of five tumours showed invasion into mediastinal fat or pleura but, otherwise, all were well circumscribed. No metastases were present. Histologically, the tumours showed a biphasic pattern with solid carcinomatous areas merging gradually with a spindle cell component. Lymphocytes were rare. Cytological atypia and mitotic activity were variable in the solid areas, but slight or absent in the spindle cell component. On immunohistochemistry, the tumours showed expression of cytokeratin, vimentin and/or epithelial membrane antigen, both in the carcinomatous and spindle cell components. In two cases, actin expression was also present in both components. In one case, chromogranin, S100 protein, glial fibrillary acidic protein and neuron-specific enolase were expressed in at least some cells of both components. None of the patients had myasthenia gravis. All patients are alive without evidence of recurrence or metastasis.〈section xml:id="abs1-3"〉〈title type="main"〉ConclusionMetaplastic carcinoma of the thymus is a distinct clinicopathological entity that should be distinguished from the usually benign medullary thymomas and from the clinically aggressive carcinosarcomas and sarcomatoid carcinomas.
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  • 3
    ISSN: 1365-2559
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Aims : Classical Hodgkin's lymphoma (cHL) rarely coexists as composite lymphoma with B-cell non-Hodgkin's lymphoma (B-NHL). We characterized 12 cases of composite marginal zone B-cell lymphoma (MZBL) and cHL by immunohistochemistry and molecular biology.Methods and results : Eight patients had gastric MZBL of mucosa-associated lymphoid tissue (MALT)-type, in five cases with a diffuse large B-cell lymphoma component. Concurrent cHL was observed either in the stomach wall, regional, or distant lymph nodes. One patient each had composite pulmonary/thyroid MZBL of MALT-type and cHL. In two cases, nodal composite MZBL and cHL was observed. cHL displayed features of mixed cellularity type in 10 cases, while in two cases only scattered Hodgkin- and Reed–Sternberg (H/RS) cells were noted. H/RS cells expressed CD30, multiple myeloma oncogene 1 protein (MUM1P), p53 (100%), CD15 (58%), CD20 (58%) and Epstein–Barr virus-associated LMP1 (50%). No t(11;18)(q21;q21) was detected in composite MZBL of MALT-type and cHL.Conclusions : MZBL and cHL may occur as composite lymphoma, possibly reflecting clonal lymphoma progression. Derivation from extranodal MZBL of MALT-type should be excluded in cases in which a diagnosis of primary extranodal cHL is considered.
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  • 4
    ISSN: 1437-160X
    Keywords: Rheumatoid arthritis ; Ki 67 ; Synovial lining cells ; B and T lymphocytes ; Dysmorphic follicle ; Antigen-presenting cells
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract We analysed the proliferative activity of synovial lining cells (SLCs), the distribution of proliferating B and T lymphocytes and the relationship of proliferating B and T lymphocytes to the pattern of antigen-presenting cells (APCs) within the rheumatoid synovial tissue (n=21). The immunohistochemical detection of the proliferation-associated antigen Ki 67 revealed low proliferative activity of SCL with and without expression of the Kim 8 (CD 68) antigen. Ki 67-positive B lymphocytes could be observed within secondary follicles (2/21), in small follicular dendritic reticulum cell (FDC)-containing follicle-like aggregates (7/21) and near the enlarged synovial intima (6/21). Ki 67-positive T lymphocytes could be detected in T-lymphocyte aaggregates (8/21), in the vicinity of blood vessels (18/21) and within the enlarged synovial intima (15/21). Semiquantitative analysis showed a strong correlation between the numbers of Ki 67-positive B lymphocytes and FDCs and between the numbers of Ki 67-positive T lymphocytes and interdigitating dendritic reticulum cells (IDC). There were significant differences in the number of Ki 67-positive B and T lymphocytes, IDCs and FDCs between the two groups of rheumatoid arthritis (RA) patients with different local clinical activity. These findings demonstrate a low proliferation of SLCs with and without expression of the monocyte-specific antigen Kim 8 and imply that B and T lymphocyte proliferation occurs in the presence of FDCs and IDCs. These results indicate that the RA synovial tissue is a site for antigen-dependent proliferation and maturation of B and T lymphocytes. The atypical pattern of FDC distribution within the rheumatoid synovial tissue “dysmorphic follicle” may be regarded as morphological substrate for a dysmaturation compartment of B lymphocytes leading to pathogenetic autoimmune phenomena in RA patients.
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  • 5
    ISSN: 1437-160X
    Keywords: Key words Psoriatic arthritis ; Cellular infiltrate ; Macrophage ; T lymphocyte ; Interleukin-8
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Psoriatic arthritis is an inflammatory arthropathy that ultimately can lead to joint destruction. In this study, we investigated the immunophenotype of the inflammatory cells and the expression of interleukin-8 (IL-8), which is the hallmark chemoattractant cytokine of psoriasis in synovial membranes from patients exhibiting active psoriatic synovitis (n=9). The tissue samples were examined by immunohistochemistry, Western blot analysis and in situ hybridisation. The inflammatory infiltrate consisted predominantly of CD3+ T lymphocytes, with a higher proportion of CD4+ than CD8+ T lymphocytes in six cases. CD3+ T lymphocytes were focally distributed near small blood vessels and the enlarged synovial intima. CD1+ interdigitating reticulum cells were not detected. CD22+ B lymphocytes and plasma cells were found in small aggregates without KiM4+ follicular dendritic cells. KiM8+ macrophages were located in the synovial intima and were distributed in a diffuse pattern near the synovial lining cells. CD15+ neutrophil granulocytes were detected in four cases. They were preferentially located in the vicinity of blood vessels and the synovial intima. IL-8 was found at a high level in the synovial lining cells and to a lesser extent in cells located in the perivascular areas. Immunofluorescence double staining showed IL-8 to be expressed in KiM8+ multinucleated giant cells, KiM8+ macrophages and CD3+ T lymphocytes. IL-8 receptor A was demonstrated in the synovial lining and in macrophages and lymphocytes. IL-8 was detected by immunoblot analysis of the synovial tissue at 8.4 kD. Employing in situ hybridisation, IL-8 mRNA was strongly and preferentially expressed in the synovial intima, as well as in macrophages and lymphocytes. The immunophenotype of the psoriatic arthritis inflammatory cells shows great similarity to the inflammatory infiltrate found in the synovial tissue of patients with rheumatoid arthritis. The preferential expression of IL-8 and IL-8 mRNA in the enlarged synovial intima and in lymphocytes and macrophages suggests that IL-8 exerts its action through activated mononuclear cells and T lymphocytes. It seems to play a role in regulating leucocyte traffic into the enlarged synovial intima and may contribute to the aggressive synovitis of patients with psoriatic arthritis.
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  • 6
    ISSN: 1437-160X
    Keywords: Key words Rheumatoid arthritis ; sICAM-1 ; Endothelial cells ; Synovial tissue
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The objective of this research was to investigate the cellular source of soluble ICAM-1 (siCAM-1) from rheumatoid synovial tissue (RS) and its relation to sICAM-1 in synovial fluid (SF) and serum, and to study the expression of ICAM-1 in isolated cells of RS. sICAM-1 was determined by using the enzyme-linked immunosorbent assay (ELISA) and Western blot analysis in supernatants from RS cultured for short periods (n = 19), in SF (n = 7) and in serum (n = 19). ICAM-1 expression, vascularization and inflammatory infiltration (CD3, CD68, CD22) were characterized immunohistochemically in cytospin preparations (n = 18), cryosections (n = 18) and in conventionally stained paraffin sections (n = 19) of RS. The degree of RS vascularization was analysed morphometrically in immunohistochemically stained cryosections (factor VIII related antigen). We found 90-kD sICAM-1 in supernatants of cultured cells, in SF and in sera. sICAM-1 in cellular supernatant correlated significantly (P 〈 0.01) with SF sICAM-1. The amount of sICAM in cellular supernatants showed no correlation to the score of inflammatory infiltration, but correlated significantly (P 〈 0.001) with the vascularization index of RS. The percentage of ICAM-1-expressing cells correlated significantly (P 〈 0.001) with the percentage of CD68-positive macrophages, but not with CD3- and CD22-positive lymphocytes. Macrophages, multinucleated giant cells and endothelial cells exhibited a higher expression of ICAM-1 as compared to lymphocytes and fibroblasts. The differential expression of ICAM-1 on infiltrating leucocytes and resident cells of RS indicates a functional role of ICAM-1 in the local inflammatory process. SF sICAM-1 originated in RS, but serum sICAM-1 did not. Shedding of sICAM-1 by RS was independent of inflammatory infiltration, but depended on the degree of vascularization, indicating that endothelial cells are the major source of sICAM-1 in RS.
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  • 7
    ISSN: 1432-1440
    Keywords: Gastric cancer ; Intestinal and diffuse tumor types ; CD44v6 ; Lymph node metastases
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract In 42 human gastric adenocarcinomas of intestinal (n=25) and diffuse types (n=17) the expression of CD44v6 splice variants was investigated immunohistochemically and compared with the pattern of lymphogenic tumor spreading. Distinct differences were observed between the two cancer types: 92% of intestinal-type tumors expressed CD44v6 as in the intestinal metaplasia in chronic atrophic gastritis, while v6 expression occurred in only 17% of diffuse-type cancers. The analysis of RNA expression confirmed the immunohistochemical data. Intestinal-type cancers yielded a much more complex pattern of amplification products hybridizing to exon v6 than did normal mucosa, whereas diffuse-type tumors did not express exon v6. Also the pattern of lymphogenic spreading was quite different between the two cancer types: in diffuse-type tumors only a sinus carcinosis without CD44v6 expression was observed in a significantly higher number of lymph nodes than in intestinal-type cancers, which showed in particular infiltrative lymph node metastases always with CD44v6 expression as in the primary tumors. When infiltrative lymph node invasion occurred in v6-negative diffuse-type cancers, v6 neoexpression was also demonstrable in the lymph node metastases. Additionally, the number of infiltrative lymphogenic metastases increased with more extensive v6 expression in primary gastric cancers of both types. These data suggest that the expression of CD44v6 isoform is important for the infiltrative spreading of tumor cells into lymph nodes. Addtionally, the phenotypic similarities in v6 expression between intestinal metaplasia and intestinal-type cancers, but not of tumors of diffuse type, may support the Correa hypothesis.
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  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Virchows Archiv 430 (1997), S. 355-364 
    ISSN: 1432-2307
    Keywords: Key words Autoimmunity ; Thymus ; Thymoma ; Acetylcholine receptor ; Aetiology
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  Various studies over the last 25 years in Man and animal models have revealed many steps in the pathogenesis of myasthenia gravis (MG) which is now considered the classical organ specific, autoantibody mediated and T cell dependent human autoimmune disease. Though not a disease entity, MG is associated with pathological alterations of the thymus in about 80% of cases. These are described here with reference to distinct models of autoimmunization against the acetylcholine receptor (AChR). In MG with thymitis, intrathymic production of AChR-specific autoantibodies is the result of a classical antigen-driven immune reaction that occurs completely inside the thymus and probably involves AChR on myoid cells as the triggering (myasthenogenic) antigen. Genetic factors contribute essentially to the pathogenesis of this form of MG. In thymoma-associated MG genetic factors are probably of marginal significance. Neither intratumour autoantibody production nor T cell activation seem to occur and the AChR is not the myasthenogenic antigen. Instead, abnormal neurofilaments that share epitopes with the AChR and other autoantigen targets in paraneoplastic MG are expressed in thymomas and may trigger autoantigen-specific, non-tolerogenic T cell selection by molecular mimicry. These data support the hypothesis that initial steps in the pathogenesis of most MG cases take place within abnormal thymic microenvironments, be they inflammatory or neoplastic. Where these initial steps occur in MG cases without thymic pathology is not known. Likewise, the factors involved in the initial triggering of MG remain enigmatic in all MG subtypes.
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  • 9
    ISSN: 1432-0533
    Keywords: Key words Simian immunodeficiency virus ; Neuropathology ; Longitudinal analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract To determine the onsets and specificities of neuropathological features observed after simian immunodeficiency virus (SIV) infection of macaques, brains of 19 clinically unaffected rhesus monkeys (group A) were examined after intervals ranging from 1 to 48 weeks post-infection and compared to 8 animals with AIDS (group B) as well as to 8 uninfected controls. Based on morphological and virological parameters, seven patterns specific for SIV infection of the central nervous system (CNS) were discerned. In both groups of infected but not control animals, we found mononuclear aggregates in meninges, perivascular space, and choroid plexus stroma (designated pattern 1), isolated infected cells within CNS parenchyma (pattern 2), axonal degeneration (pattern 3), spongy change (pattern 4), microglial proliferation (pattern 5), and small vessel proliferation (pattern 6). SIV encephalitis (pattern 7) was only evident in animals with clinically evident disease. Changes characteristic of patterns 3, 5 and 6 appeared to be chronic and non-progressive, whereas lesions of patterns 1, 2 and 4 appeared to have progressed in animals with AIDS. The main component of mononuclear aggregates in animals of group A were lymphocytes, in contrast to animals of group B, in which macrophages dominated the inflammatory infiltrates. Altogether, our results demonstrate that subtle leukoencephalopathy was a specific feature of clinically silent as well as clinically evident phases of SIV infection. This might explain the neurological impairment of HIV-positive non-AIDS individuals.
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  • 10
    ISSN: 1432-1963
    Keywords: Schlüsselwörter Gastrales MALT-Typ-Lymphom ; Biopsie ; Resektat ; Graduierung ; Key words Gastric MALT-type lymphoma ; Biopsy ; Surgical specimen ; Grading
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary Diagnostic und therapeutic management of gastric lymphomas of the mucosa-associated lymphoid tissue type (MALT-type lymphomas) is often based exclusively on the evaluation of biopsy material. To evaluate the diagnostic value of gastric biopsies in gastric MALT-type lymphomas, biopsies – on average six per patient – and subsequent surgical specimens of 64 patients were compared at the Institute of Pathology, Unversity of Würzburg. Tumor diagnosis and tumor gradind were assessed. Using biopsy specimens, primary gastric MALT-type lymphomas were correctly diagnosed by local pathologists in 69% of cases, but correctly graded as low-grade, high-grade or secondary high-grade lymphomas in only 41%. When immunohistochemistry and molecular biological techniques were applied in addition to conventional histology, diagnosis of gastric MALT-type lymphoma was achieved in biopsies in 95% of cases at the Institute of Pathology Würzburg, but correct grading in only 73%. In secondary high-grade MALT-type lymphomas, both components – the high-grade and the low-grade component – were identified in gastric biopsies in only 33% of cases. Diagnostic accuracy in gastric lymphomas based on biopsies is limited by biopsy artefacts, but improved by using immunohistochemistry and molecular biological techniques. Particularly in secondary high-grade MALT-type lymphomas the correct diagnosis is often missed when using biopsies, due to a low number of biopsy specimens.
    Notes: Zusammenfassung Die Diagnostik gastraler MALT-Typ-Lymphome stützt sich heute fast ausschließlich auf Magenbiopsien. Um deren diagostische Aussagekraft zu bestimmen, wurden im Referenzzentrum für Lymphknotenpathologie Würzburg bei 64 Patienten mit gastralem MALT-Typ-Lymphom durchschnittlich 6 präoperative Magenbiopsien mit dem konsekutiven Gastrektomieproäparat verglichen. Anhand der Biopsie wurde durch den primär befundenden Pathologen ein MALT-Typ-Lymphom in 69% der Fälle richtig diagnostiziert, in 41% korrekt in niedrigmaligne, hochmaligne und sekundär hochmaligne graduiert. Am Referenzzentrum erhöhte sich die Treffsicherheit der Biopsie durch Anwendung zusätzlicher Verfahren (Immunhistologie, Molekularbiologie) auf 95% beziehungsweise 73%. Dennoch wurden bei den sekundär hochmalignen Lymphomen auch hier nur in 33% sowohl die hoch- als auch die niedrigmaligne Tumorkomponente erfaßt. Die diagnostische Aussagekraft von Magenbiopsien in gastralen Lymphomen ist durch Biopsieartefakte eingeschränkt, kann jedoch durch immunhistochemische und molekularbiologische Verfahren erhöht werden. Insbesondere sekundär hochmaligne Lymphome lassen sich aufgrund der limitierten Anzahl von Biopsien präoperativ oft nicht hinreichend erkennen.
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