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Biomedical subjects

R De Vos

Publications and source records attributed to R De Vos.

At least 55 records · Page 3Linked to original sources

t(9;22)(q22-31;q11-12) is a consistent marker of extraskeletal myxoid chondrosarcoma: evaluation of three cases.

Three cases of extraskeletal myxoid chondrosarcoma with typical histologic and ultrastructural features were investigated cytogenetically. All three cases showed a reciprocal chromosome translocation characterized as t(9;22)(q22-31)(q11-12), thus confirming the findings in three previously karyotyped cases of extraskeletal myxoid chondrosarcoma in the literature. These data add significantly to the evidence of t(9;22) being diagnostic for extraskeletal myxoid chondrosarcoma. Other previously published cases with a range of complex karyotypes were less well defined morphologically. In cases with limited diagnostic material this karyotype might facilitate distinction from myxoid liposarcoma, which consistently shows t(12;16). Clear cell sarcoma, Ewing's sarcoma/primitive neuroectodermal tumor, and desmoplastic round cell tumor also show involvement of chromosome 22 with formation of a hybrid gene between the Ewing's sarcoma gene on band q12 and a transcription factor gene. Whether rearrangement of the Ewing's sarcoma gene is also present in extraskeletal myxoid chondrosarcoma is not clear at present. Cloning of the (9;22) translocation might provide important clues to the pathogenesis of this type of chondrosarcoma.

Adult↗

Physiological consequences of loss of plasminogen activator gene function in mice.

Indirect evidence suggests a crucial role for the fibrinolytic system and its physiological triggers, tissue-type (t-PA) and urokinase-type (u-PA) plasminogen activator, in many proteolytic processes. Inactivation of the t-PA gene impairs clot lysis and inactivation of the u-PA gene results in occasional fibrin deposition. Mice with combined t-PA and u-PA deficiency suffer extensive spontaneous fibrin deposition, with its associated effects on growth, fertility and survival.

Animals↗

Transient expression of tenascin in experimentally induced cholestatic fibrosis in rat liver: an immunohistochemical study.

This study describes the sequential changes in tenascin expression in hepatic fibrosis induced by bile duct ligation (BDL) in the rat. Two days after BDL, tenascin was strongly expressed in the matrix surrounding interlobular bile ducts and also between proliferating ductules. From day 7 onwards, its distribution was restricted to the connective tissue-parenchymal interfaces where ductular proliferation was still active. A markedly increased number of desmin- and alpha-smooth muscle actin (alpha-smA)-positive cells, considered myofibroblasts, was noted around interlobular bile ducts and between proliferating ductules during periductal fibrogenesis. Type IV collagen and laminin were strongly expressed on the basement membranes of proliferating ductules, and contributed to the development of newly formed fibrous septa. The transient expression of tenascin around interlobular bile ducts in the early phase of BDL may be related to the onset of periductal fibrosis or to the mitogenic response of the biliary epithelium. The expression of tenascin between 'proliferating' ductules in contrast to its absence from 'mature' fibrous areas suggests a transient role in early matrix organization. Furthermore, alpha-smA-positive cells may modulate the synthesis of extracellular matrix components.

Actins↗

Alveolar soft-part sarcoma: evidence for its myogenic origin and for the involvement of 17q25.

A typical case of alveolar soft-part sarcoma was examined using ultrastructural, immunohistochemical and cytogenetic methods. Immunohistochemical stains were performed on frozen sections and showed strong desmin expression with the three anti-desmin antibodies used. In addition, the tumour cells were weakly positive for vimentin and myosin. Neural markers were negative. Chromosomal analysis showed consistent involvement of 17q25--an abnormality which has been reported in another alveolar soft-part sarcoma. The histogenesis of alveolar soft-part sarcoma is still debatable but our findings support a myogenic origin. The finding of an apparently identical chromosomal abnormality in two of three thus far examined cases of alveolar soft-part sarcoma is of interest and must await further confirmation, but it may result in the identification of a chromosomal marker for this enigmatic tumour and thus pave the way for further molecular elucidation.

Adult↗

A new epithelial cell type in the human cornea.

PURPOSE: To study the expression of intermediate filaments in the human cornea. METHODS: Light and electron microscopic and immunohistochemical studies were performed on 20 corneas from subjects of various ages. RESULTS: A hitherto unrecognized epithelial cell population emerged from the immunohistochemical studies. Epithelial cells were invariably present in the superior cornea, whereas the nasal, temporal, and inferior segments almost lacked these cells. They were situated at the transition between peripheral cornea and limbus, and occurred as small groups in the basal epithelium. On electron microscopy, they were recognized by their marginated nuclear chromatin, large nucleoli, prominent bundles of intermediate filaments, and numerous hemidesmosomes and desmosomes. Immunohistochemistry on frozen sections revealed a unique intermediate filament make-up: ie, strong co-expression of vimentin and cytokeratin 19; other intermediate filaments, including cytokeratins 3, 4, 6, 7, 8, 10, 13, and 18 were negative. Finally, the cells lacked ultrastructural and immunohistochemical features of melanocytes, neuroendocrine cells, Langerhans' cells, and leukocytes. CONCLUSIONS: A new epithelial cell type in the human cornea is described with characteristic morphologic and immunohistochemical features. According to their particular segmental distribution, restricted localization at the junction between cornea and limbus, and expression of an "early" intermediate filament profile, it is tempting to speculate that they represent stem cells of the human cornea. Further studies are aimed to characterize their phenotype and function more extensively.

Aged↗

Hepatic expression of type A and type B receptors for tumor necrosis factor.

We have examined the in-situ distribution of type A and type B receptors for tumor necrosis factor (TNF) in normal and diseased human liver biopsy specimens. In normal liver tissue, no or very small amounts of TNF receptors were found. In acute and chronic inflammatory liver diseases, a strong up-regulation of the expression of both TNF receptors was found on hepatocytes, bile duct epithelium, sinusoidal lining cells and mononuclear inflammatory cells. With immunoelectronmicroscopy, all these cells showed cytoplasmic, in addition to membranous staining, suggesting active synthesis of the receptor or, alternatively, internalization of the receptor and its ligand. This up-regulated expression of both type A and type B receptors for TNF was similar in acute and chronic active hepatitis, and was not related to the etiology of the liver disease, nor restricted to areas of liver inflammation. Our results indicate that hepatocytes, sinusoidal endothelial cells, bile duct epithelial cells and mononuclear inflammatory cells, by displaying receptors for TNFs, represent target cells for both these cytokines. Up-regulated expression of type A and type B receptors for TNFs endows these cells with augmented responsiveness for the pleiomorphic biological activities of these cytokines during liver injury.

Biopsy, Needle↗

Whipple's disease: a histological, immunocytochemical and electronmicroscopic study of the immune response in the small intestinal mucosa.

Whipple's disease is a multisystem disorder with protean manifestations and with poorly understood aetiopathogenesis. It is unclear how the immune system reacts, whether it functions normally or not, whether it protects the organism or is defeated in one way or another by the 'Whipple bacillus'. The purpose of our study was to assess humoral and cellular immunity at the level of the intestinal mucosa. This histochemical, immunocytochemical and electronmicroscopic study, based on 16 cases, has shown that the changes in components of the mucosal immune system in Whipple's disease are quite different from normal. The phagocytic capacity of the macrophages, assessed microscopically, is abnormal, the number of intra-epithelial lymphocytes is increased, the CD 4/CD 8 cell ratio is decreased and the IgM positive cells in the lamina propria outnumber the IgA positive cells. These changes may be inter-dependent.

Adult↗

Malignant rhabdoid tumour of the liver. A case report.

A case of primary malignant rhabdoid tumour of the liver occurring in a 5-month-old girl is reported. Histologically the neoplasm presented the 'typical' features as described in malignant rhabdoid tumour arising in the kidney. In addition, some areas of the tumour showed a 'pseudoglandular' growth pattern. Immunohistochemistry revealed the neoplastic cells to be intensively positive for vimentin and for cytokeratin 19. Variable immunoreactivity for cytokeratin polypeptides 7, 8 and 19 was also detected. On electronmicroscopy the neoplastic cells contained bundles of intermediate filaments, tonofilaments and intercellular junctions. These findings are suggestive of a primitive epithelial differentiation.

Biomarkers↗

Hemangiopericytoma of the head and neck: a report of four cases and a literature review.

Hemangiopericytoma is an infrequent vascular tumor that rarely appears in the head and neck. The nasal cavity and the paranasal sinuses are most often involved. Four cases are added to the literature and some important features are stressed. The clinical presentation is aspecific. Diagnosis is made only by careful histological examination with special stainings (reticulin, immunohistochemistry with Ulex Europaeus) and gives an idea about the grading. Treatment with radical surgery, if possible, is effective while preoperative embolisation can reduce the risk of hemorrhage. The median follow-up of the present cases is only 3 years. During this period no recurrence was observed. We suggest that more radical resections can probably reduce the local recurrence rate. However lifetime clinical follow-up is warranted since late recurrences have been reported in almost half of the patients.

Adult↗

Ultrastructural characteristics of novel epithelial cell types identified in human pathologic liver specimens with chronic ductular reaction.

Previous immunohistochemical studies on human liver biopsies with chronic ductular reaction revealed the presence of "small cells" with bile-duct type cytokeratin profile in the periportal area. This study identified similar cells by electron microscopy. The authors studied 13 human liver specimens with various liver diseases, but all characterized by chronic ductular reaction. In all specimens, variable numbers of "small cells" with common epithelial characteristics were identified in the periportal area. They could be classified into three types. Type I cells showed an oval cell shape and oval nucleus, early or established formation of junctional complexes with adjacent cells, a full assortment of cytoplasmic organelles, and bundles of tonofilaments. Type II cells showed features of bile-duct cell differentiation, including lateral interdigitations, apical microvilli, basal pinocytotic vacuoles, and basement membrane formation. In contrast, type III cells displayed additional features indicating hepatocellular differentiation, such as a more prominent nucleus, formation of a hemicanaliculus, and glycogen rosettes. It is concluded that these small cells of epithelial nature display variable differentiation characteristics of either bile-duct type cells or hepatocytes. These findings support the existence of bipotential progenitor epithelial cells in human liver. They may have implications for liver regeneration and carcinogenesis.

Cholestasis↗

True histiocytic neoplasm of Langerhans' cell type.

Malignant histiocytic neoplasms of dendritic cell lineage are rare and most are derived from the dendritic cells of the T-cell and B-cell areas of the lymph node, respectively. Only one case of a malignant histiocytic neoplasm of Langerhans' cells, the dendritic cell of the skin, has been reported. We report the occurrence of a true histiocytic neoplasm of Langerhans' cell type in a 23-year-old female patient. The diagnosis of this highly aggressive neoplasm is supported by histochemical, immunohistochemical, ultrastructural, and genotypic analysis--techniques which allow differentiation from malignant melanoma and large cell anaplastic lymphoma.

Adult↗

Light chain deposition disease of the liver associated with AL-type amyloidosis and severe cholestasis.

A 67-year-old man with a 3-month history of jaundice presented with hepatomegaly. Laboratory studies revealed abnormal liver tests with raised bilirubin. Renal function was normal. Endoscopic retrograde cholangiopancreatography revealed normal extrahepatic bile ducts. Liver biopsy showed severe bilirubinostasis and a typical bile infarct. Laminar and globular deposits of PAS-positive diastase-resistant non-congophilic material were observed in the sinusoidal walls. In addition, congophilic material was detected in the portal tracts. Immunohistochemistry revealed the presence of lambda-light chain deposits both in the sinusoids and in the portal tracts. Collagens type I and IV and fibronectin appeared markedly increased in the perisinusoidal space. On electron microscopy, the deposited material in the Disse spaces was mainly composed of fibrils indistinguishable from amyloid, admixed with small amounts of granular electron-dense material. The similarities of light chain deposition disease and AL amyloidosis are discussed.

Aged↗

Expression of interferon-gamma receptor in normal and pathological human liver tissue.

Using in situ immunohistochemistry and a specific monoclonal antibody (mcab R1G10), we analyzed the expression of the human interferon-gamma receptor (HuIFN-gamma R) and its topographical distribution in normal liver biopsies and in biopsies with various inflammatory liver diseases. In normal liver tissue, mcab R1G10 reacted weakly with sinusoidal and vascular endothelial cells, while hepatocytes were distinctly negative. In pathological conditions, mcab R1G10 produced membranous, cytoplasmic and/or perinuclear staining of hepatocytes, in a topographical distribution which varied according to the type of liver disease. In acute hepatitis, R1G10-positive hepatocytes were diffusely distributed throughout the liver parenchyma, and showed strong cytoplasmic, as well as membranous and perinuclear reactivity. In chronic persistent hepatitis, weak membranous staining was found on a number of scattered hepatocytes in acinar zone 1, with more pronounced expression on single hepatocytes in acinar zone 3. In chronic active hepatitis and in active cirrhosis, a diffuse weak membranous reactivity throughout the liver parenchyma was accompanied by enhanced R1G10 expression in areas of inflammation in acinar zone 1. With immunoelectronmicroscopy, R1G10 reactivity was found on the peripheral cell membrane and on the microvillous canalicular cell membrane of hepatocytes in a strikingly discontinuous manner. In the cytoplasm, the reaction product was detected on the cisternae of the rough endoplasmic reticulum and on small vesicles which were especially abundant in the perinuclear area. Our results demonstrate the absence of HuIFN-gamma R on hepatocytes in the normal liver, and its de novo expression during inflammatory liver disease. These findings indicate that hepatocytes, by displaying the HuIFN-gamma R, may act as target cells for the immunoregulatory action of IFN-gamma during liver inflammation.

Biopsy, Needle↗

Cells with neuroendocrine features in regenerating human liver.

Regeneration of liver tissue in man after submassive necrosis is reflected by replicating features in hepatocytes, and by a remarkably increased number of bile duct structures that are thought to transdifferentiate into true functioning hepatocytes. Similar to the bile ductule-related "oval cells" in rats, human bile ductular cells may therefore serve as "facultative stem cells" that become activated when hepatocyte regeneration is insufficient or inhibited. Our recent demonstration of neuroendocrine features in proliferating bile ductules in cholestatic liver disease prompted us to perform a similar immunohistochemical and electron microscopical study on regenerating human liver tissue after submassive liver necrosis. In the earliest stages of regeneration, bile ductular cells and small, singular cells in the periportal area expressed chromogranin-A and contained dense-cored, secretory granules. It is tempting to speculate that the scattered singular cells represent the human equivalent of the bipotential progenitor cells in the rat. In later stages of regeneration, these singular cells were no longer evident, suggesting their differentiation into other cell types. In these cases, neuro-endocrine cells corresponded to proliferating bile ductules and to scattered, typical hepatocytes, located near portal tracts and in regenerating nodules. In all cases, proliferating bile ductules displayed the neural cell adhesion molecule (NCAM). These data further support our hypothesis that the substance(s) produced in the dense cored secretory granules may play a role in the growth and/or differentiation of liver cells through an autocrine and or paracrine pathway.

Antibodies, Monoclonal↗

Distribution of non-lymphoid, inflammatory cells in chronic HBV infection.

Non-lymphoid cells play a key role in the initiation and maintenance of cellular immune responses. Using in-situ immunohistochemical techniques and a panel of monoclonal antibodies (mcabs) reactive with B5-fixed, paraffin-embedded liver biopsies, we analysed the non-lymphoid cell component in inflammatory infiltrates in 20 cases of chronic hepatitis B virus (HBV) infection. In addition, lymphocyte subsets and HLA-DR antigens were studied. Mcab KP1 labelled scattered Kupffer cells, which variably expressed HLA-DR antigens. Their random distribution and lack of significant topographical association with lymphocytes suggest that classical Kupffer cells do not play a major role in cell-mediated immune reactions. On the other hand, mcab Mac387 was unreactive with normal liver tissue but labelled HLA-DR+ dendritic cells in areas of intralobular inflammation. On (immuno)electron microscopy, these Mac387+ dendritic cells were situated in the Disse space, where they formed close contacts with lymphocytes. Similar dendritic cells were situated at the edge of portal tracts in cases of chronic active, but not chronic persistent hepatitis. Immunostaining on serial frozen sections revealed their close topographical association with cytotoxic/suppressor T-cells, suggesting that Mac387+ HLA-DR+ dendritic cells play an immunomodulatory role in the effector arm of the cellular immune response that takes place in the periphery of portal tracts and the lobular parenchyma, and that involves activation and proliferation of cytotoxic T cells. Finally, large Mac387- HLA-DR+ dendritic cells expressing the LN2 marker were situated amidst helper/inducer T-cells in the centre of severely inflamed portal tracts.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigen-Presenting Cells↗

Leukemia-associated lymph node infiltrates of plasmacytoid monocytes (so-called plasmacytoid T-cells). Evidence for two distinct histological and immunophenotypical patterns.

The medium-sized mononuclear cell with plasmacytoid features, formerly known as "T-associated plasma cell" or "plasmacytoid T cell," has recently been shown to express several myelomonocyte and monocyte-macrophage associated antigens, suggesting a monocytic origin, and it has been renamed "plasmacytoid monocyte." The present study describes the clinical and pathological features of two patients with generalized lymphadenopathy and leukemia (chronic myelomonocytic leukemia in Case 1, and acute non-B, non-T lymphoblastic leukemia in Case 2), and whose lymph node biopsies showed large numbers of plasmacytoid monocytes associated with the leukemic infiltrates. Case 1 was strikingly similar to three previously reported cases of so-called "plasmacytoid T cell" lymphoma, all associated with a myeloproliferative disorder. In our case, the destructive growth pattern of the plasmacytoid monocytes and the de novo expression of CD5 on these cells favored their neoplastic nature; the sharing of some markers of plasmacytoid monocytes with the myelomonocytic infiltrate suggested they were part of the tumoral proliferation. In Case 2, plasmacytoid monocytes displayed an immunophenotype guide similar to that reported in reactive conditions and were antigenically unrelated to the leukemic cells; plasmacytoid monocyte clusters occurred also in the lymphoid parenchyma spared by the leukemic infiltrate. These findings led us to interpret the large numbers of plasmacytoid monocytes in this second case as a tumor-associated host reaction.

Aged↗

Neuroendocrine features of reactive bile ductules in cholestatic liver disease.

Various cholestatic liver diseases are accompanied by a striking increase in the number of bile ductules. This so-called ductular reaction is thought to arise both from ductular metaplasia of hepatocytes and from proliferation of pre-existing bile ductules. Previous studies have shown that these reactive bile ductules differ from their normal counterpart in enzyme and immunohistochemical make-up. Using monoclonal antibodies directed to neuroendocrine markers and immunohistochemistry, we found that reactive bile ductules in cholestatic liver disease display neuroendocrine features. In all cases of primary biliary cirrhosis (PBC), primary sclerosing cholangitis (PSC), extrahepatic obstruction, and acute hepatitis A, reactive bile ductules expressed the neural cell adhesion molecule (N-CAM) and reacted with monoclonal antibody A2B5. Both N-CAM and the ganglioside, recognized by A2B5, are restricted to neuroendocrine cells and tissues. In all but four of these cases, the same bile ductules expressed chromogranin-A, present in the matrix of neuroendocrine granules. Furthermore, in three cases of longstanding cholestasis, scattered periportal hepatocytes expressed chromogranin-A but not N-CAM. Other neuroendocrine markers such as neuron-specific enolase, synaptophysin, or myelin-associated glycoprotein were lacking from both bile ductules and hepatocytes. The neuroendocrine phenotype of bile ductules and hepatocytes was confirmed on electronmicroscopy, demonstrating various numbers of dense-cored, neuroendocrine granules near the peripheral cell membrane in bile ductules as well as in cells intermediate between hepatocytes and bile ductular cells. In 10 cases of normal liver tissue without ductular reaction, bile ductules lacked neuroendocrine markers except in two cases in which very weak reactivity for chromogranin-A was observed. These findings illustrate the presence of a new, neuroendocrine cell type that emerges in the liver during cholestasis. Elucidation of the significance of the neuroendocrine substance(s) produced in the dense cored granules of reactive bile ductules awaits their isolation and characterization. We can speculate that this molecule plays an autocrine or paracrine regulatory role in the process of ductular metaplasia of hepatocytes or growth of bile ductules.

Antigens, CD↗