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L H Rademakers

Publications and source records attributed to L H Rademakers.

At least 37 records · Page 2Linked to original sources
PubMed1993

Ultrastructure of the cortical epithelium of the rat thymus after in vivo exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD).

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is known for inducing cortical atrophy in the rat thymus. The present study was conducted to provide ultrastructural evidence for the cortical epithelium to be a target for TCDD in vivo. Juvenile male Wistar rats were orally intubated once with either 50 or 150 micrograms/kg TCDD and killed 4 or 10 days thereafter. Major changes were found in the cortical thymic epithelium. First, a relative shift occurred from "pale" to darker cortical epithelial cell types, as judged by their nuclear and cytoplasmic electron density. This effect was most prominent at 10 days after exposure to 150 micrograms/kg TCDD. The increased electron density of the cortical epithelium indicates an altered state of cellular differentiation. Secondly, at the 150 micrograms/kg dose level focal epithelial cell aggregates were seen both at day 4 and day 10 after administration. This aggregation may either be compound induced or represent a secondary event to the collapse of the thymic stroma. Thirdly, increased vacuolation of cortical epithelial cells was apparent. This effect is interpreted as a consequence rather than a cause of thymocyte depletion from the cortex. This study indicates that TCDD exposure affects the cortical epithelium of the rat thymus at a high dose level. Electron microscopy reveals that the differentiation of epithelial cells is altered. In addition, epithelial cell aggregates are formed.

Animals↗
PubMed1993

The cortical epithelium of the rat thymus after in vivo exposure to bis(tri-n-butyltin)oxide (TBTO). An (immuno)histological and ultrastructural study.

Bis(tri-n-butyltin)oxide (TBTO) induces cortical atrophy in the rat thymus. We studied the potential involvement of the cortical epithelium in TBTO-induced thymotoxicity by (immuno) histology and electron microscopy. Juvenile male Wistar rats were orally intubated once with either 30 or 90 mg/kg TBTO and sacrificed 4 or 10 days later. A dose-dependent thymic atrophy occurred. Anti-keratin labelling showed epithelial cell aggregation in some animals at 10 days after exposure to 90 mg/kg TBTO, when recovery of the thymus was apparent. At the ultrastructural level, a relative shift was observed from "pale" to darker epithelial cell subtypes at the 30 mg/kg dose level, both at day 4 and day 10 after intubation. This phenomenon was not observed after exposure to 90 mg/kg TBTO. Both the altered keratin distribution and the increased electron density of the epithelium probably represent non-specific phenomena. The present morphological observations support the concept that TBTO affects the thymus via its action on lymphoid cells rather than on the epithelial compartment.

Animals↗
PubMed1993

Accumulation of iron in erythroblasts of patients with erythropoietic protoporphyria.

We have studied the iron metabolism in nine patients with erythropoietic protoporphyria (EPP) and three patients with sideroblastic anaemia (SA). All, except one EPP patient were iron deficient. The SA patients had a secondary haemochromatosis. The bone marrow aspirates of patients with SA and also three patients with EPP had a high incidence of ring sideroblasts. Ultrastructural examination of the bone marrow consistently showed finely dispersed electron-dense deposits localized in mitochondria of erythroblasts in all patients with EPP and SA. Mitochondrial electron energy-loss spectroscopy (EELS) indicated identical iron compounds in erythroblasts of all EPP and SA patients. These findings indicate that the mitochondrial iron utilization is disturbed in EPP and SA. The observation of mitochondrial iron deposition in erythroblasts in EPP and SA suggests that this failure is not of pathognomonic value for diagnosis of SA, but is apparently the result of an inefficient haem synthesis, in EPP due to a defective ferrochelatase. The mitochondrial iron deposition does not depend on the iron status (iron overload or iron deficiency) of the EPP patient.

Adult↗
PubMed1993

Involvement of the omental lymphoid organ in the induction of peritoneal immunity against tumor cells.

The omental lymphoid organ (OLO) is a part of the greater omentum composed of vascularized spots containing lymphocytes, plasma cells and macrophages located in a regular pattern between fat cells. To gain insight in the involvement of the OLO in the induction of immunity against tumor cells in the peritoneal cavity, we studied the penetration of tumor cells into the OLO after intraperitoneal, subcutaneous and intravenous injection. Furthermore we analyzed the tumoricidal activity of macrophages isolated from the OLO. Our results indicate that the OLO is only infiltrated by tumor cells directly from the peritoneal cavity, but not by subcutaneously or intravenously injected tumor cells unless they have reached the peritoneal cavity. Bromodeoxy-uridine labelled tumor cells can be detected in the OLO within 10 min after i.p. injection. The penetration is facilitated by the induction of fenestrations between the mesothelial cells (lining the OLO) after intraperitoneal injection of the tumor cells. These fenestrations can also be seen after nonspecific stimulation of the peritoneal cavity. Macrophages isolated from the OLO of mice immunized against syngeneic as well as allogeneic tumor cells express a significant cytotoxicity, which (at least in the syngeneic situation) precedes the cytotoxicity of the macrophages isolated from the peritoneal cavity. In conclusion, our data support the hypothesis that immune reactions against intraperitoneally injected tumor cells are initiated in the OLO leading to 'peritoneal immunity' against these tumor cells.

Animals↗
PubMed1992

Dark and light zones of germinal centres of the human tonsil: an ultrastructural study with emphasis on heterogeneity of follicular dendritic cells.

The cellular composition of the dark and light zones of germinal centres in human tonsils was quantitatively determined by electron microscopy. In addition to the well known germinal-centre B-cells, we defined the cleaved blast as a new distinct cell type in the germinal centre. The dark and the light zones clearly differed in their content of lymphoid and non-lymphoid germinal-centre cells. The dark zone was characterized by higher frequencies of cleaved blasts and small centroblasts, a higher blast-centrocyte ratio and a higher incidence of mitotic figures. In contrast, the light zone had higher frequencies of centrocytes, centroplasmacytoid cells, lymphocytes and follicular dendritic cells (FDC) and an inverted blast-centrocyte ratio. Seven distinct appearances of FDC (FDC.1-FDC.7) could be recognized on the basis of their ultrastructure. The distribution pattern of these subtypes differed between the dark and light zone. The undifferentiated subtypes FDC.2 and FDC.3 predominated in the dark zone. In contrast, the highly differentiated subtypes FDC.4 and FDC.5 were present at a much higher density in the light zone. These findings suggest that the dark and light zones are different compartments with regard to proliferation and differentiation of germinal-centre B-cells and that both compartments have a specific microenvironment influenced by FDC.

B-Lymphocytes↗
PubMed1992

Cellular composition of germinal centers in lymph nodes after HIV-1 infection: evidence for an inadequate support of germinal center B lymphocytes by follicular dendritic cells.

Germinal centers in lymph nodes with follicular hyperplasia from 15 patients with HIV-1 infection were analyzed by qualitative and quantitative electron microscopical methods and compared with control follicular hyperplasia (FH). Using a pattern recognition method, two main clusters were recognized within the germinal centers of HIV and FH lymph nodes on the basis of the relative frequencies of small centroblast and centrocytes. All FH lymph nodes and 6 HIV-1 lymph nodes (HIV-Clu-1) were placed in cluster 1; 9 HIV-1 lymph nodes (HIV-Clu-2) formed cluster 2. Germinal centers in the HIV-Clu-2 lymph nodes were characterized by a cell composition of predominantly lymphoid blasts and decreased numbers of centrocytes, but without altered numbers of mitotic figures. The frequency distribution of ultrastructurally distinct FDC subtypes differed between these clusters. In HIV-Clu-2 the frequencies of FDC types with an undifferentiated and regressive morphology occurred at a higher frequency, whereas FDC types with a highly differentiated morphology had a lower frequency. We conclude that 9 out of 15 lymph nodes with HIV-1 associated follicular hyperplasia show changes in FDC morphology indicative of a less differentiated functional stage of FDC. The changes in FDC morphology are closely associated with changes in the germinal center B-cell population resulting in an inverted blast to the centrocyte ratio.

Dendritic Cells↗
PubMed1992

Simian immunodeficiency virus (SIVsm) infection of cynomolgus monkeys: effects on follicular dendritic cells in lymphoid tissue.

We studied follicles in sections of lymph nodes and spleen from cynomolgus monkeys (Macaca fascicularis) after infection with simian immunodeficiency virus (SIVsm), by (immuno)histology and (immunogold) electron microscopy. Also isolated follicular dendritic cells (FDC) were investigated. Histology showed ranged from follicular hyperplasia to follicle fragmentation. FDC showed desmin and vimentin, characteristic of mesenchymal cells. Except for two animals who got experimental chemotherapy in the first postinfection period, the cells expressed SIV gag p28 protein. Electron microscopy showed SIVsm-like particles in the germinal centers. A number of cell types in the germinal center, including FDC, showed tubuloreticular structures, indicative of alpha-interferon synthesis during an antiviral response. In immunogold electron microscopy, SIV p28 label was observed on the surface of FDC, on SIVsm-like particles, and in the cytoplasm of macrophages. A relatively high density of CD8-positive cells (T cytotoxic-suppressor phenotype) was observed around and in germinal centers, especially areas depleted of FDC. Cells immunoreactive for serine esterase granzyme-B, a protein occurring in granules of cytotoxic cells, occurred around germinal centers, but not in germinal centers at areas where FDC and SIV p28 label localized. This argues against a role of cytotoxic T cells in mediating follicle destruction.

Animals↗
PubMed1992

Interdigitating cells in the rat thymus during cyclosporin A treatment: ultrastructural observations.

Major Histocompatibility Complex (MHC) class II-positive cells are almost completely absent in the rat thymic medulla after cyclosporin A (CsA) exposure. This phenomenon has been related to alterations in the medullary interdigitating cells (IDCs), representing either down-modulation of RT1 class II antigen on persistent IDCs, or actual disappearance of IDCs. To resolve this issue, we performed an ultrastructural study of the rat thymic medulla during CsA treatment (15 mg/kg body weight/day CsA subcutaneously for 7 to 14 days). At day 7 after exposure, only very few IDCs could be identified. They showed an abnormal ultrastructural morphology as judged by inconspicuous membrane interdigitations and lack of Birbeck granules. At day 14, the number of IDCs was larger. At this time, the IDCs had a normal ultrastructure, except for the almost complete absence of Birbeck granules. We conclude that CsA causes an initial depletion of IDCs from the thymic medulla. The ultrastructural morphology of the few IDCs present suggests an immature character. New IDC immigrants appear in the medullary area already during CsA treatment, indicating early recovery.

Animals↗
PubMed1991

Lymphokine-activated killer-cell-mediated killing of WiDr colon carcinoma cells is inhibited by K562 erythroleukemia cells.

Lymphokine activated killer (LAK) activity was induced in human peripheral mononuclear blood cells by human recombinant interleukin-2. Monocytes were required for optimal rapid proliferation of cells with LAK activity. They had no influence on the expression of tumoricidal activity by the LAK cells. The effector cells killed K562 erythroleukemia cells and WiDr colon cells differently, i.e. contact areas with WiDr cells were limited, whereas the contact areas between effector cells and K562 cells were much longer. Using mixtures of hot and cold target cells it was shown that effector cells preferably bind with K562 cells, impeding the binding of WiDr cells. Differences in expression of cytotoxicity of LAK cells against WiDr and K562 cells respectively was also observed after culturing the LAK cells for a relatively longer period. Cytotoxicity against WiDr was maximal at 3-16 days after starting LAK cell generation, whereas cytotoxicity against K562 was kept constantly high for at least 21 days. The addition of biological response modifiers [PHA and anti-CD3 antibody (OKT3)] during the LAK cell induction also had different effects on the expression of LAK activity against WiDr and K562 cells. Whereas PHA, in combination with rIL-2 had no significant influence on the cytotoxicity against WiDr cells, the cytotoxicity against K562 was significantly inhibited. Addition of anti-CD3 antibody diminished the cytotoxicity against WiDr target cells and had no influence on the cytotoxicity against K562 cells.

Carcinoma↗
PubMed1991

Human follicular dendritic cells: isolation and characteristics in situ and in suspension.

Follicular dendritic cells (FDC) in human tonsils, either in situ in follicular germinal centres or isolated from tissue, were characterized by immunohistochemical, enzyme cytochemical and electron microscopical methods. Using polyclonal and monoclonal antibodies, expression of DRC-1, Ki-M4, HLA-DR, CR1, C1q antigens, a macrophage marker, and surface IgG and IgM were found on isolated FDC and on FDC in situ. None of these reagents proved to be specific for FDC, e.g. the FDC-directed antibodies DRC-1 and Ki-M4 labelled B lymphocytes in cytofluorography. Enzyme cytochemical staining revealed activities of non-specific esterase, acid alpha-naphthylacetate esterase and ATPase in germinal centres and in freshly isolated FDC. Immunohistochemistry demonstrated a weak expression of CD4 by a fraction of isolated FDC, which was confirmed by two-colour immuno-staining and immuno-electron microscopy.

5'-Nucleotidase↗
PubMed1991

Parathymic lymph nodes during growth and rejection of intraperitoneally inoculated tumor cells.

The omental lymphoid organ (OLO) is a part of the greater omentum composed of vascularized milky spots situated between fat cells and containing lymphocytes, plasma cells and macrophages. We analysed the disappearance of intraperitoneally injected tumor cells from the peritoneal cavity and their infiltration into and disappearance from the OLO and the parathymic lymph nodes (PTLN) that drain the peritoneal cavity. After intraperitoneal inoculation of irradiated syngeneic tumor cells, they were visible in the OLO within 24 h. After 3 days, no tumor cells were seen anymore, but there were many macrophages that had phagocytosed tumor cells. After intraperitoneal inoculation of nonirradiated syngeneic tumor cells, a solid growing tumor mass developed in the OLO. The PTLN were also invaded by these nonirradiated tumor cells within 24 h as transfer of cell suspensions of these lymph nodes into naive mice leads to the death of the recipient mice due to tumor growth. However, from day 6 onwards, after tumor inoculation, these lymph nodes contained no tumor cells, despite progressive tumor growth intraperitoneally and in the liver and lungs. In allogeneic mice, tumor cells were rejected in the OLO after 7-10 days. Simultaneously, the number of lymphocytes and macrophages increased and a plasma cell reaction developed. The PTLN did not have tumor-inducing potency at any stage after intraperitoneal tumor injection. This study suggests, that the PTLN are more effective in the (local) eradication of tumor cells than the OLO. Still, considering its immunological potential, the OLO might be important as 'inducer' of immunological reactions in the peritoneal cavity.

Animals↗
PubMed1990

Early involvement of hepatic parenchymal cells in erythrohepatic protoporphyria? An ultrastructural study of patients with and without overt liver disease and the effect of chenodeoxycholic acid treatment.

Liver biopsy specimens obtained from two groups of erythrohepatic protoporphyria patients were studied histopathologically and ultrastructurally. Group 1 comprised seven erythrohepatic protoporphyria patients with a normal liver histology; from two patients liver biopsy specimens were available before and after 1 yr of chenodeoxycholic acid treatment. Group 2 consisted of four patients with a history of liver disease and liver histopathology; three patients were observed before and after 1 yr of chenodeoxycholic acid treatment. Liver specimens of nine kidney transplant donors served as controls. Unlike the morphology at the light microscopic level, the ultrastructure of hepatic parenchymal cells was affected in both groups of erythrohepatic protoporphyria patients. In both groups the nuclei, endoplasmic reticulum, lateral plasma membranes and bile canaliculi were altered. Collagen fibers were frequently present. In addition, in group 2 bile thrombi and intracytoplasmic protoporphyrin crystals were observed. After chenodeoxycholic acid administration, the latter feature had diminished. It is concluded that (a) in erythrohepatic protoporphyria ultrastructural changes are present in the hepatic parenchymal cells even in early stages of the disease. Changes in bile canalicular ultrastructure suggest a defective hepatic excretory function, probably caused by the toxic effect of protoporphyrin. (b) Chenodeoxycholic acid administration causes no distinct improvement of the ultrastructure of organelles in the hepatic parenchymal cell or the bile canalicular system but may decrease crystalline protoporphyrin deposition in the liver.

Adolescent↗
PubMed1989

Ultrastructural cytochemistry of non-specific esterase in murine peritoneal macrophages.

Non-specific esterase (NSE) activity was demonstrated in glutaraldehyde-fixed monolayers of murine peritoneal macrophages. Using 2-naphthylthiol acetate (NTA) as substrate and Fast Blue BB as coupling agent a strong osmiophilic reaction product was obtained. The reaction product was observed as electron-dense dots covering cisterns of the rough endoplasmic reticulum, Golgi saccules and vesicles, or as large aggregates in lysosomes. Using alpha-naphthyl butyrate (ANB) as substrate and hexazotized pararosaniline as coupling agent the osmiophilic reaction product was observed extracellularly on the plasma membrane as an electron-dense continuous layer, whereas intracytoplasmic staining of lysosomes was rare. Substitution of the coupling agents in the respective media resulted in a slight reaction with the ANB medium whereas with the NTA medium reaction product was observed only in lysosomal structures. The substrate specificity of the different types of esterases was confirmed after isoelectric focusing on thin-layer polyacrylamide gels. The results indicate that in murine peritoneal macrophages different types on NSE are detected with NTA and ANB, having distinct ultrastructural localizations.

Animals↗