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Biomedical subjects

R De Vos

Publications and source records attributed to R De Vos.

At least 73 records · Page 4Linked to original sources

Thyroid hormones and the hepatic handling of bilirubin. I. Effects of hypothyroidism and hyperthyroidism on the hepatic transport of bilirubin mono- and diconjugates in the Wistar rat.

The effects of thyroidectomy and of thyroid hormone administration on the hepatic transport of endogenous bilirubin were investigated in the Wistar R/APfd rat. Hypothyroidism resulted in an enhanced hepatic bilirubin UDP-glucuronosyltransferase activity and in a decreased p-nitrophenol transferase activity. It caused a cholestatic condition with a 50% decrease in bile flow and bile salt excretion, and an increased proportion of conjugated bilirubin in serum. The biliary output of unconjugated and monoconjugated bilirubins decreased in parallel by about 65%, whereas the excretion rate of the diconjugate dropped by only 47%, resulting in an increased di- to monoconjugate ratio in bile. Hyperthyroidism was characterized by a decreased bilirubin and an increased p-nitrophenol transferase activity, and by an augmented bilirubin output in bile. The output of unconjugated and monoconjugated bilirubins increased in parallel by about 50 or 100%, whereas the excretion of the diconjugate increased by only 20 to 50%, depending on the dose of thyroxine administered; this resulted in a decreased di- to monoconjugate ratio in bile. A linear positive relationship was found between bilirubin UDP-glucuronosyltransferase activity and the ratio of bilirubin di- to monoconjugates present in bile or formed by in vitro incubation of liver homogenates at low concentration of bilirubin (10 to 15 microM), indicating that bile pigment composition is mainly determined by the conjugation activity in the liver. The inverse relationship observed between hepatic beta-glucuronidase activity and the ratio of di- to monoconjugates in bile warrants further investigation to analyze whether this enzyme activity also plays a possible role in the changes in bile pigment composition in hypo- and hyperthyroid rats.

4-Nitrophenylphosphatase↗

Primary malignant fibrous histiocytoma of the esophagus.

A 59-year-old man was admitted to the hospital for dysphagia and fever. Esophagogram and upper gastrointestinal endoscopy revealed a polypoid mass in the midesophagus. Subtotal esophagectomy, cervical esophagogastrostomy, and lymph node dissection were performed. The histological diagnosis of the tumor was malignant fibrous histiocytoma. An area of severe epithelial dysplasia was found in the esophageal mucosa 3 cm under the tumor.

Esophageal Neoplasms↗

Plasmacytoid monocytes (so-called plasmacytoid T cells) in granulomatous lymphadenitis.

Immunohistochemical evidence that the plasmacytoid T cell is closely related to the blood monocyte has been reported, and the term plasmacytoid monocyte has been proposed to describe this cell. The present study was undertaken to analyze the presence and distribution of plasmacytoid monocytes in human reactive lymph nodes showing epithelioid cell reactions. Numerous plasmacytoid monocytes (detected by a panel of monoclonal antibodies) were found in the majority of the lymph nodes studies, usually in close topographical association with epithelioid cells and multinucleated giant cells. The present findings suggest that plasmacytoid monocytes may give rise to epithelioid cells. This is further supported by the ultrastructural similarities between plasmacytoid monocytes and plasmacytoid epithelioid cells, a cell type that has been identified previously in granulomas and considered a direct precursor of the classical epithelioid cell.

Granuloma↗

Spontaneous healing of Langerhans cell histiocytosis (histiocytosis X).

A 3-month-old male infant presented with pallor, hepatomegaly (4.5 cm), splenomegaly (1.5 cm), anaemia (Hb 6 g/dl) and thrombocytopenia (16 X 10(9)/l). A liver biopsy was diagnostic for Langerhans cell histiocytosis (histiocytosis X). The patient's lymphocytes, co-cultured with neonatal lymphocytes, were positive for virus-like particles without reverse transcriptase activity. The hepatomegaly diminished after 6 months and a second liver biopsy showed decreased histiocytic infiltration. A second viral blood culture remained negative. After 14 months, the hepatomegaly had disappeared completely and there were no more abnormal haematological or clinical findings.

Histiocytes↗

Immunoelectron microscopic localization of hepatic transferrin receptors in human liver with and without iron overload.

The expression of transferrin receptors (TfR's) has been investigated in eight liver biopsy specimens (four from patients without demonstrable iron and four from patients with iron storage due to primary hemochromatosis (HC)) using immunoelectron microscopy to demonstrate TfR's by the simultaneous application of two specific monoclonal antibodies (OKT9 and B3/25) to tissue chopper sections. In the four specimens without iron overload, hepatocytes, but not sinusoidal lining cells, stained positively and immunoreactivity was mainly localized in the cytoplasm. Positively stained cisternae of the endoplasmic reticulum indicated synthesis of the TfR. The presence of TfR's on segments and coated invaginations of the sinusoidal membrane and in small, but otherwise unidentified vesicles in the cytoplasm is compatible with endo-/exocytotic transport and recycling of TfR's as demonstrated by biochemical studies. Occasional positively stained material in canalicular lumina together with positively stained canalicular microvilli and pericanalicular vesicles suggest that transcellular transport may be an additional pathway for TfR's. In three biopsies showing severe iron overload due to HC, TfR immunoreactivity was completely absent. The remaining specimen showing HC, exhibited relatively mild iron overload and showed only a few positively stained hepatocytes. This supports the previously reported disappearance of hepatic TfR expression in HC when iron overload is severe.

Hemochromatosis↗

Immunoelectron microscopic investigation of HLA-DR-positive dendritic cells at the dermo-epidermal junction in skin disorders associated with the deposition of immune complexes.

HLA-DR-positive dendritic cells present at the dermo-epidermal junction in skin disorders associated with the deposition of immunoglobulins and/or complement factors in the skin biopsy are investigated ultrastructurally. They demonstrate long, slender cytoplasmic processes, an indented nucleus, and strikingly dilated cisternae of the endoplasmic reticulum. HLA-DR antigen is present on the plasma membrane and within some of the dilated cisternae. These findings further support our previously formulated hypothesis that these cells represent a functionally active stage of antigen-presenting cells.

Antigen-Antibody Complex↗

A recommended procedure for ultrastructural immunohistochemistry on small human tissue samples.

Various fixation and staining procedures for the demonstration of surface and cytoplasmic antigens have been described. An immunostaining procedure was sought that would allow the demonstration of these antigens, especially in small human tissue samples at the ultrastructural level. A modification and adaptation of the technique of Eldred, Zucker, Karten, and Yazula (J Histochem Cytochem 31:285, 1983) was applied on several varieties of human tissue, including liver, skin, and lymphoid tissue, using monoclonal and polyclonal antibodies in an indirect peroxidase procedure. In this way a reliable and generally applicable procedure was developed that satisfied the following demands: Use of a universal fixative that allows preservation of the antigenicity of various antigens; Adequate penetration of the tissue by the immunological reagents; Optimal preservation of subcellular structures; and Possibility to store the tissue samples for considerable periods of time.

Antibodies, Monoclonal↗

A case of histiocytosis X-central type. Histological, immunohistochemical and electronmicroscopical analysis.

We report a case of Histiocytosis X (HX) associated with a high bone marrow and peripheral blood monocytosis in a 70 yr-old man. The histiocytic clusters in the skin showed the characteristics of epidermal Langerhans cells (LC): positivity for OKT6, OKIa1, ATP-ase and presence of Birbeck granules. Histiocytes in all other locations showed positivity for OKM1, OKIa1, acid P-ase and absence of Birbeck granules. The circulating monocytes were also negative for OKT6 and ATP-ase and lacked Birbeck granules. From these data we assume that the proliferation of monocytes in the bone marrow was the primary event, resulting in the release of large numbers of circulating monocytes and histiocytic proliferation in various tissues. These histiocytes acquired differing characteristics according to the microenvironment in which they underwent their final maturation. In the skin they differentiated into cells presenting the morphological, enzyme-and immunohistochemical characteristics of LC.

Aged↗

Immature sinus histiocytosis. Light- and electron-microscopic features, immunologic phenotype, and relationship with marginal zone lymphocytes.

The light-microscopic, ultrastructural, and immunohistochemical features of immature sinus histiocytosis were studied in 10 lymph nodes with the histologic picture of toxoplasmic lymphadenitis and compared with the features of lymphoid cells present in the marginal zone of the splenic white pulp. Areas of immature sinus histiocytosis consisted largely of medium-sized lymphoid cells with markedly irregular nuclei and abundant pale cytoplasm. Using a panel of monoclonal antibodies, the predominating lymphoid cells were found to carry the B-cell phenotype B1+Ba1-sIgM+sIgD-OKIa1+. Admixed were variable numbers of larger, blastic lymphoid cells, small lymphocytes, histiocytic elements, and polymorphonuclear granulocytes. The marginal zone of the splenic white pulp was composed of a similar mixture of cells, and marginal-zone lymphocytes demonstrated an analogous immunohistochemical phenotype. Our results indicate that immature sinus histiocytes are B-lymphoid cells that are closely related to marginal zone lymphocytes. As such, immature sinus histiocytes may have a role similar to that of marginal-zone lymphocytes, which have been claimed to transport antigens or immune complexes toward the follicular center or to serve as precursors of plasma cells. We suggest that immature sinus histiocytosis represents an abnormal expansion of the marginal zone, normally present at the sinusoidal pole of lymphoid follicles. The reason for this marginal-zone hyperplasia, recognized as immature sinus histiocytosis in a variety of reactive lymph node conditions, may be a maturation arrest in the normal development of immature sinus histiocytes into small, sIgM+ sIgD+ lymphocytes.

Histiocytes↗

New ultrastructural marker in hepatocytes in non-A, non-B viral hepatitis.

A new ultrastructural cytoplasmic marker designated as type 2, and distinct from type 1 previously associated with NA-NB hepatitis in chimpanzees, was found in hepatocytes of two patients and of one experimentally infected chimpanzee. These cases represent a minority of all cases we studied as presumed NA-NB viral hepatitis. Type 2 marker consists of tubular structures composed of an assembly of ring-like units coated with smaller uniform fragments, accumulated in different patterns in dilated cisternae of the endoplasmic reticulum. Preliminary data using immunofluorescence with NA-NB hepatitis convalescent serum and antiserum against fibrinogen are reported. Type 2 marker may represent a different agent or a different reaction pattern to one agent of NA-NB viral hepatitis. Its features are compared with those of hepatitis B.

Adult↗

Morphology of liver cell tight junctions in ethinyl estradiol induced cholestasis.

Using freeze-fracture techniques the junctional complex of the hepatocytes in female rats is studied after ethinyl estradiol induced cholestasis. The gap junctions are not changed in this situation in contrast to the altered pattern found in extrahepatic bile duct obstruction. The more or less parallel tight junctional strands around the canalicular lumen are converted into a irregular loose network after estradiol treatment in a similar way as in extrahepatic cholestasis. These modifications in the geometrical arrangement of the strands suggest an increase permeability through the tight junctions so that a backward diffusion of biliary components through intercellular escape is possible.

Animals↗

Human non-A, non-B hepatitis: ultrastructural alterations in hepatocytes.

Ultrastructural investigation of liver biopsies from two patients with non-A, non-B hepatitis revealed cytoplasmic and nuclear alterations in the hepatocytes. The lesions in both patients, one with acute and one with chronic hepatitis, were similar and distinct from those previously described in other forms of hepatitis. These findings are compared with the reported findings in chimpanzee liver after inoculation with non-A, non-B infective material. The intranuclear findings are similar to the aggregations of 20-27 nm particles described in some infected chimpanzees, and the cytoplasmic alterations seem to be similar to the cytoplasmic structures and tubular arrangements reported in other inoculated chimpanzees. A striking finding of this study is the presence of both alterations together in the same biopsy in two different patients, suggesting that they represent a different stage of viral infection or different parts of the viral agent. It still remains to be proved that the ultrastructural particles indeed contain antigen(s) of the non-A, non-B hepatitis virus. The nuclear and cytoplasmic alterations are, however, characteristic for non-A, non-B hepatitis and are useful as ultrastructural hallmarks of this form of hepatitis.

Adult↗