Search PubMed⌕ Search

Biomedical subjects

V Desmet

Publications and source records attributed to V Desmet.

At least 37 records · Page 2Linked to original sources
PubMed1998

Primary liver tumour of intermediate (hepatocyte-bile duct cell) phenotype: a progenitor cell tumour?

A 57-year-old female patient presented with painless obstructive jaundice and mild mesogastric pain; she was in good general condition on admission. Abdominal ultrasonography revealed diffuse tumoral invasion of the liver, suggesting diffuse metastases. A liver biopsy showed a tumour with a trabecular growth pattern, composed of uniform relatively small cells, very suggestive of an endocrine carcinoma. Additional immunohistochemical stains, however, did not show any endocrine differentiation, but showed positivity for both hepatocyte-type cytokeratins (cytokeratin 8 and 18) and bile duct-type cytokeratins (cytokeratin 7 and 19). In addition, parathyroid hormone-related peptide, shown to be a good marker for cholangiocarcinoma, was immunoreactive. Electron microscopy revealed tumour cells with an intermediate phenotype: the cells clearly showed hepatocyte features on one hand and bile duct cell features on the other hand. Nine days after admission, the patient died due to liver failure and hepatic encephalopathy. Autopsy excluded another primary tumour site. Overall, this tumour was a primary liver tumour with an intermediate phenotype and with a very rapid clinical course. The intermediate (between hepatocyte and bile duct cell) phenotype suggests an immature progenitor cell origin, which is concordant with a rapid clinical course. This type of tumour has not been described previously and provides additional evidence for the existence of progenitor cells in human liver.

Bile Ducts↗
PubMed1998

Ductular reaction and its diagnostic significance.

Ductular reaction refers to an increased number of ductules (the finest ramifications of the biliary tree), accompanied by polymorphonuclear leukocytes and an increase in matrix, leading to periportal fibrosis and eventually biliary cirrhosis. It is a phenomenon that is seen in a variety of liver diseases, such as acute and chronic cholestasis and variable degrees of parenchymal necrosis. Ductular reaction has gained new interest because of its relationship with putative human liver progenitor cells. The existence of progenitor cells in a quiescent organ such as the liver, although still controversial, is important for the understanding of biological processes, such as embryogenesis, carcinogenesis, and regeneration. This article provides a diagnostic algorithm: Starting from the phenomenon of ductular reaction, portal tract and parenchymal changes that give diagnostic clues are systematically described.

Algorithms↗
PubMed1997

Adhesion molecules in vernal keratoconjunctivitis.

AIMS/BACKGROUND: Adhesion molecules play a key role in the selective recruitment of different leucocyte population to inflammatory sites. The purpose of the present study was to investigate the presence and distribution of adhesion molecules in the conjunctiva of patients with vernal keratoconjunctivitis (VKC). METHODS: The presence and distribution of adhesion molecules were studied in 14 conjunctival biopsy specimens from seven patients with active VKC and in four normal conjunctival biopsy specimens. We used a panel of specific monoclonal antibodies (mAbs) directed against intercellular adhesion molecule-1 (ICAM-1), intercellular adhesion molecule-3 (ICAM-3), lymphocyte function associated antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leucocyte adhesion molecule-1 (ELAM-1) In addition, a panel of mAbs were used to characterise the composition of the inflammatory infiltrate. RESULTS: In the normal conjunctiva, ICAM-1 was expressed on the vascular endothelium only, LFA-1 and ICAM-3 on epithelial and stromal mononuclear cells, and VLA-4 on stromal mononuclear cells. The expression of VCAM-1 and ELAM-1 was absent. The number of cells expressing adhesion molecules was found to be markedly increased in all VKC specimens. This was concurrent with a heavy inflammatory infiltrate. Strong ICAM-1 expression was induced on the basal epithelial cells, and vascular endothelial cells. Furthermore, ICAM-I was expressed on stromal mononuclear cells. LFA-1 and ICAM-3 were expressed on the majority of epithelial and stromal infiltrating mononuclear cells. VLA-4 expression was noted on stromal mononuclear cells. Compared with controls, VKC specimens showed significantly more ICAM-3+, LFA-3+, LFA-1+, and VLA-4+ cells. VCAM-1 and ELAM-1 were induced on the vascular endothelial cells. CONCLUSIONS: Increased expression of adhesion molecules may play an important role in the pathogenesis of VKC.

Adolescent↗
PubMed1996

Paucity of intrahepatic bile ducts, solitary kidney and atrophic pancreas with diabetes mellitus: atypical Alagille syndrome?

UNLABELLED: A child with the tentative diagnosis of Alagille syndrome is reported. Additional renal abnormalities are unilateral kidney agenesis and a kidney with subcortical cysts with decreased function. At the age of 5 years, insulin-dependent diabetes mellitus developed, with the pancreas being atrophic and negative pancreatic islet cell antibodies. CONCLUSION: This observation extends the picture of Alagille syndrome and suggests an overlap with renal-hepatic-pancreatic dysplasia (Ivemark syndrome).

Alagille Syndrome↗
PubMed1996

An immunohistochemical study of topical cyclosporine in vernal keratoconjunctivitis.

PURPOSE: To determine the immunomodulating effects of topical cyclosporine on the immune cells in the conjunctival biopsy specimens obtained from patients with active vernal keratoconjunctivitis. METHODS: We studied six patients who had severe active vernal keratoconjunctivitis. Each patient was given topical cyclosporine 2% eyedrops four times daily. A 2 x 2-mm limbal conjunctival biopsy specimen was obtained from each patient before and three weeks after treatment. Using a panel of monoclonal and polyclonal antibodies and immunohistochemical techniques, we analyzed the conjunctival immune cells before and after cyclosporine treatment. RESULTS: Three weeks after topical cyclosporine treatment, there was marked clinical improvement and a statistically significant reduction in the number of epithelial and stromal class II MHC+ cells, UCHL1+ T cells, and stromal IgA+ and IgG+ plasma cells. The mean number of cells before and after therapy, respectively, were: class II MHC+ (epithelium), 31.5 +/- 13.1 and 8.3 +/- 5.6 (P = .031); class II MHC+ (stroma), 77.0 +/- 28.7 and 24.7 +/- 17.5 (P = .031); UCHL1+ T cells (epithelium), 24.5 +/- 14.1 and 4.2 +/- 2.9 (P = .031); UCHL1+ T cells (stroma), 78.7 +/- 31.1 and 44.5 +/- 27.5 (P = .031); IgA+ plasma cells, 66.7 +/- 32.1 and 22.2 +/- 7.8 (P = .031); and IgG+ plasma cells, 37.3 +/- 30.0 and 9.0 +/- 6.4 (P = .031). There was a statistically insignificant decrease in the epithelial class II MHC+ dendritic Langerhans cells, epithelial and stromal KP1+ macrophages, stromal OPD4+ helper/inducer T cells, and stromal L26+ B cells. The numbers of IgE+ plasma cells and mast cells were unaltered. CONCLUSION: The clinical improvement in vernal keratoconjunctivitis after topical cyclosporine therapy may result from its immunomodulating effect on the components of cell-mediated and humoral immune responses. In contrast, the drug has no immunomodulatory effect on mast cells and IgE-mediated allergic response.

Administration, Topical↗
PubMed1996

'Undifferentiated progenitor cells' in focal nodular hyperplasia of the liver.

Focal nodular hyperplasia is a tumour like lesion, characterized by a central fibrous scar with irradiating fibrous septa that surround hyperplastic nodules and contain multiple bile ductules. The origin of the bile ductular structures is not clear. Recently, we found evidence for the existence of human counterparts of rat oval cells (potential stem cells) that have the ability of differentiating towards both bile duct cells and hepatocytes. These cells were found in regenerating human liver as well as in chronic cholestatic conditions. Because cholestatic features are seen in focal nodular hyperplasia, we initiated an immunohistochemical study on 23 surgical specimens using antibodies specific for cytokeratins 7 and 19 (bile duct type cytokeratins), OV6 (rat oval cell marker), chromogranin-A (shown to be positive in reactive bile ductules and human oval-like cells) and neural cell adhesion molecule--NCAM (shown to be positive in reactive bile ductules) to investigate whether 'undifferentiated progenitor cells' are also present in focal nodular hyperplasia. Electronmicroscopy was applied in five cases. Bile ductules invariably showed immunoreactivity for CK7 and 19, OV6, chromogranin-A and NCAM. In addition, small individual cells with an oval nucleus and a small rim of cytoplasm, in the vicinity of the septa, were immunoreactive for chromogranin-A, CK7 and 19 and OV6. These cells were hardly recognizable on routine light microscopy. Clusters of periseptal hepatocytes, seemingly in continuity with bile ductular structures, had a transitional phenotype: they stained positive for chromogranin-A, CK7 and OV6 and sometimes formed liver cell rosettes. The number of OV6-positive hepatocytes was greater than the number of chromogranin-A and CK7 positive hepatocytes. This indicates that, in human liver, OV-6 is not purely a marker of progenitor cells. Ultrastructurally, small immature cells, highly resembling rat oval cells, were recognized in the vicinity of septa. In addition, transitional cells displaying characteristics both of hepatocytes and bile duct cells were also present. These results confirm the presence of 'undifferentiated progenitor cells' in focal nodular hyperplasia and suggest that the ductular reaction in these lesions results, at least partly, from activation of these cells.

Animals↗
PubMed1996

Heparan sulfate proteoglycan expression in chronic cholestatic human liver diseases.

The mechanism of bile ductular reaction and accompanying fibrogenesis depends on interactions of ductular cells with the matrix and growth factors. Heparan sulfate proteoglycans (HSPGs) are essential cofactors in cell-matrix adhesion processes, in cell-cell recognition systems, and in receptor-growth factor interactions. We used monoclonal antibodies specific for the cell surface HSPGs (syndecans, glypican), for matrix HSPG (perlecan), and for heparan sulfate carbohydrate (HS) to investigate their immunohistochemical expression in 20 specimens with chronic cholestatic liver disease and in five normal human liver specimens. Because activated hepatic stellate cells (HSC are a major source of fibrosis in the liver, we also examined HSPG expression in primary cultures of human activated HSC using immunocytochemistry and Western blotting and for syndecan-1 also Northern blotting. In comparison with bile ductular cells of normal liver, reactive ductules in chronic cholestasis were marked by an elevated expression of syndecan-1, surrounded by an increased perlecan expression. In acinar zone 1, large stimulated macrophages and HSC, present in increased numbers, were strongly positive for syndecan-3. Cultured HSC showed a membranous staining pattern for syndecan-1, syndecan-3, and heparan sulfate, and in addition intracellular staining for syndecan-2, -3, and 4. Perlecan immunoreactivity was detected as intercellular strings. Western blotting revealed positive bands with all antibodies and Northern blotting for syndecan-1 was also positive. These results show that cultured human HSC can synthesize all four syndecans, glypican, and perlecan. These data reveal changes in the expression of syndecan-1, syndecan-3, and perlecan in human chronic cholestatic liver disease, that may be important in the deposition of matrix components and activation of growth factors that support ductular reaction and accompanying fibrogenesis.

Antibodies, Monoclonal↗
PubMed1996

Gastric gland heterotopia with extensive lymphoid stroma: a gastric lymphoepithelial cyst.

Benign submucosal epithelial lesions of the stomach are rare. Their morphological aspect and pathogenesis and hence classification are unclear. The literature on this subject consists mainly of case reports describing lesions such as hamartomas, gastric gland heterotopia, duplication, submucosal cystic glands, gastritis cystica profunda, and adenomyoma. We report a patient presenting with a lymphoepithelial cyst, a lesion hitherto not yet described in the stomach. This lesion was an incidental finding in a surgical specimen from a patient during surgery for gastric adenocarcinoma. The cyst was submucosal, located at a distance from the tumor, and differs from classic "gastric gland heterotopia" by the presence of extensive lymphoid stroma.

Adenocarcinoma↗
PubMed1996

Combined treatment with methotrexate and ursodeoxycholic acid in non-cirrhotic primary biliary cirrhosis.

In the treatment of patients with primary biliary cirrhosis (PBC), methotrexate (MTX) and ursodeoxycholic acid (UDCA) have both been associated with clinical, biochemical, and histologic improvement. Studies with methotrexate have only been performed in uncontrolled conditions. We conducted a prospective controlled study on the combined treatment with methotrexate and ursodeoxycholic acid, comparing the clinical, biochemical, and histologic evolution in six untreated patients with that in eight patients treated with MTX 15 mg/week in association with UDCA 500 mg/day. All patients had noncirrhotic PBC and were followed up for two years. A significant decrease of alkaline phosphatase, glutamic pyruvic transaminase, and gamma-glutamyltranspeptidase was found in the methotrexate/ursodeoxycholic acid treated-group, as compared to the control group. The clinical and histologic evolution, however, was not significantly different in the two groups. Methotrexate toxicity consisted of interstitial pneumonitis in one, of a transient rise of transaminases at three months in five, and of a significant decrease of blood platelets and white blood cells after two years of treatment. In controlled conditions, a two-year treatment with methotrexate and ursodeoxycholic acid does not produce a significant clinical or histologic benefit. Based on this experience, and taking into account the possible risks associated with this therapy, the empiric use of methotrexate cannot be recommended in patients with non-cirrhotic PBC.

Adult↗
PubMed1995

Parathyroid hormone-related peptide is expressed and rapidly inducible in human liver cell cultures that have a bile duct phenotype.

Parathyroid hormone-related peptide is the major factor responsible for hypercalcemia of malignancy. There is increasing evidence that parathyroid hormone-related peptide also plays an important role in the growth and differentiation of both neoplastic and non-neoplastic cells. Recently we found that reactive human bile ductules and cholangiocarcinomas, but not normal bile ducts, human hepatocytes nor hepatocellular carcinomas, express parathyroid hormone-related peptide and we speculated that parathyroid hormone-related peptide may function as a growth and differentiation factor for bile ductular epithelial cells. Using a specific polyclonal antibody for immunostaining and a digoxigenin-random prime-labeled probe for in situ hybridization assay, we found that only cell lines with a bile duct phenotype expressed parathyroid hormone-related peptide and its mRNA. HepG2 cells with hepatocellular phenotype (CK19-, CK7-, CK8+, CK18+, albumin+) do not express parathyroid hormone-related peptide. However, A16 (HepG2 derived cell line) expressing bile duct marker CK19, also expressed parathyroid hormone-related peptide, while hepatocyte markers CK8, CK18, CALLA and albumin were negative. In addition, the H1 cell line (adult human hepatocytes immortalized in our laboratory by SV40 DNA transfection, passaged at least 40 times and cultured for 13 months) expressed bile duct marker CK7 and parathyroid hormone-related peptide, while hepatocyte markers CK8, CK18, CALLA and albumin were negative. Previous studies demonstrated that parathyroid hormone-related peptide gene expression in keratinocytes can be modulated by serum, growth factors and cycloheximide although there is a species and cellular specificity.(ABSTRACT TRUNCATED AT 250 WORDS)

Bile Ducts↗
PubMed1995

Liver biopsy.

An overview is given of the technical aspects and the diagnostic usefulness of liver biopsy. From the clinical side, the procedures for taking liver biopsies and the various types of biopsy are summarized. The histopathology section mentions precautions for tissue sampling and processing, and reviews the diagnostically useful techniques and special microscopy procedures. Consideration is given to the factors which determine the accuracy of histopathological diagnosis, both those relating to the tissue specimen and those relating to the interpreter. Published studies on quantitation and semi-quantitation of liver biopsy findings and their reproducibility are mentioned, with a final remark on the contribution of liver biopsy to diagnosis and therapy. Emphasis is placed throughout on the necessity for close collaboration between clinician and pathologist.

Biopsy↗
PubMed1995

Giant cell rich parosteal osteosarcoma.

A parosteal osteosarcoma of the distal femur with a typical radiographic and macroscopic appearance is reported. On histology the tumour was dominated by large numbers of osteoclast-like giant cells in a fibro-osseous background and islands of immature bone. Most of the neoplastic bone lacked osteoblastic rimming. There was no spatial relationship between the giant cells and areas of haemorrhage. Signs of 'dedifferentiation' were lacking. Cytogenetic a analysis revealed telomeric associations which are frequently found in giant cell tumours of bone. Parosteal osteosarcoma may, on histological appearances, hardly be recognizable as malignant. In addition, unusual changes such as abundant giant cells may be misleading in the absence of clinico-pathological correlation.

Adult↗
PubMed1995

Angiosarcoma of the larynx.

The morphological and immunohistochemical features of a laryngeal angiosarcoma are described. Initially, the tumour was interpreted as a poorly differentiated squamous cell carcinoma. The laryngectomy specimen contained an extensive and haemorrhagic tumour consisting of irregular and dissecting vascular spaces delineated by pleomorphic endothelial cells. In addition to these obvious angiosarcomatous areas, islands of more compact growing tumour cells were present, reminiscent of a poorly differentiated squamous cell carcinoma. On immunohistochemistry, the tumour cells expressed factor VIII, Ulex europaeus I lectin, CD31 and vimentin. There was no expression of cytokeratin or epithelial membrane antigen. Angiosarcoma of the larynx is very rare and should be differentiated from a pseudo-angiosarcomatous carcinoma.

Antigens, Differentiation, Myelomonocytic↗