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Biomedical subjects

W Timens

Publications and source records attributed to W Timens.

At least 109 records · Page 6Linked to original sources

Liver metastasis model of colon cancer in the rat: immunohistochemical characterization.

Inoculation of 3 x 10(4) to 3 x 10(5) CC531 colon adenocarcinoma cells into the portal vein of syngeneic WAG/Rij rats provides a reproducible animal model of colon cancer liver metastasis with macroscopically visible tumor nodules at day 25 after inoculation. In this study, the inflammatory cell response in the liver sinusoids against locally induced metastases was also investigated using immunohistochemical methods. Host immune reactive cells accumulated in the liver sinusoids of tumor-bearing livers, especially resident Kupffer cells (KC; ED1+/ED2+), and to a lesser extent pit cells (OX8+/0X19-), T lymphocytes (OX8+/OX19+) and polymorphonuclear leukocytes (PMN; HIS48+). All these cell types may be involved in the lysis of CC531 cells in the liver, although only major histocompatibility complex class II+ monocytes (3D11+/ED1+/ED2-), but not resident KC, T lymphocytes nor PMN, accumulated at the peritumoral area between liver parenchyma and tumor foci. Especially monocytes but also PMN, lymphocytes and pit cells appeared to infiltrate the stromal tumor compartment. In view of the low cell dose needed, the rat liver metastasis model of colon cancer used in this study reflects well the human, weakly immunogenic, tumor-host relationships and provides an excellent opportunity for the study of cellular reactions related to chemo- and/or immunotherapy protocols.

Adenocarcinoma↗

Dynamics of eosinophil infiltration in the bronchial mucosa before and after the late asthmatic reaction.

We wanted to determine whether changes in bronchial hyperresponsiveness (BHR) following allergen challenge show a time relationship with inflammatory events in the airways of allergic asthmatic subjects. Lavage was performed and endobronchial biopsies were taken via the fiberoptic bronchoscope, before, and 3 and 24 h after, allergen challenge, on separate occasions, in nine dual asthmatic responders. The numbers of activated eosinophils, identified by immunohistochemistry, using the monoclonal anti-eosinophil cationic protein antibody, EG2, were significantly increased both at 3 h and at 24 h in the submucosa and bronchial lavage. A significant negative correlation was found between the number of EG2+ cells in the submucosa and in the bronchial lavage 24 h after the allergen challenge (r = -0.70). At 24 h, the amount of eosinophil cationic protein (ECP) was increased in the bronchial lavage. A significant correlation was observed between the amount of ECP at 3 h and the log provocative dose of house dust mite producing a 20% fall in forced expiratory volume in one second (PD20 HDM) (r = -0.63). The results suggest a recruitment of activated eosinophils to the submucosa and, further, to the epithelial lining, followed by degranulation. This process has already started 3 h after allergen challenge, and lasts for at least 24 h, which may result in mucosal damage and subsequent allergen-induced increase in BHR, before and after the late asthmatic reaction.

Adult↗

Deep juvenile xanthogranuloma: a lesion related to dermal indeterminate cells.

Juvenile xanthogranuloma (JXG) is considered to represent a lesion originating from histiocytes. Three cases of deeply located JXG and one case of cutaneous JXG were studied. One case with extensive mesenteric involvement presented with hypercalcemia and one case with liver involvement had hypergammaglobulinemia. Immunohistochemistry, electron microscopy, karyotyping, and DNA flow cytometry were used to determine the phenotype of the cells involved and to find further clues as to the histogenesis of these lesions. Immunohistochemically, all lesions studied expressed the CD1a antigen but showed no labeling for S-100 protein. The cells did not contain Birbeck granules. From these data it is suggested that the cells involved are of indeterminate dermal histiocyte lineage and that occurrence of deep located lesions of JXG may be due to migration of CD1 a-positive histiocytes.

Antigens, CD↗

Splenic autotransplantation and the immune system. Adequate testing required for evaluation of effect.

The risk of severe infections after splenectomy, even after many years, is now well established. In attempts to prevent these infections, spleen-saving techniques, including autotransplantation of spleen fragments, have been performed, when possible in combination with vaccination. The problem in autotransplantation is the evaluation of functional activity. The results of the tests used until now often do not seem to correlate very well with the risk of developing an overwhelming postsplenectomy infection (OPSI). This may be related to the fact that the tests used evaluate general functions, and not specific spleen-related functions, such as the capacity to mount a primary response to certain polysaccharide antigens present in the capsule of bacteria known to cause OPSI. In this review, the significance of the spleen in the human immune system is discussed and the effects of splenectomy are described, including the precautions that can be taken to diminish the risk of postsplenectomy infections and sepsis. It appears that postsplenectomy vaccination is more successful when recently developed protein-conjugated polysaccharide vaccines are used. Because the present testing of the function of spleen autotransplants is not adequate, we suggest that new tests should be developed, employing appropriate polysaccharide antigens.

Humans↗

Mediastinal germ cell tumor with secondary nongerm cell malignancy, and extensive hematopoietic activity. Pathology, DNA-ploidy, and karyotyping.

We report on a malignant germ cell tumor located in the anterior mediastinum. After chemotherapy the tumor was classified as residual teratoma with sarcomatous components. There was extensive hematopoiesis in the tumor tissue. The tumor cells had a modal chromosome number of 76; the only structural abnormality was a deletion of the long arm of chromosome 9. An i(12p) chromosome was lacking in this tumor. Karyotyping of peripheral blood and bone marrow occasionally showed metaphases with numerical and structural abnormalities, probably related to chemotherapy. The patient died within two years after the initial diagnosis, of a poorly differentiated hematopoietic malignancy, probably of myelomonocytic origin, based on morphology and the fact that non-specific esterase activity was demonstrated in the tumor cells. The karyotype of this malignancy was highly abnormal, but unrelated to that of the mediastinal malignant GCT. In this case there is no proof that the secondary malignancy was derived from the primary mediastinal malignant GCT. In view of the multiple aneuploid stem lines in the primary tumor, this possibility cannot be dismissed either.

Adult↗

Tissue distribution of the C3d/EBV-receptor: CD21 monoclonal antibodies reactive with a variety of epithelial cells, medullary thymocytes, and peripheral T-cells.

The CD21 antigen has been described to represent CR2, the receptor for the complement fragment C3d and also the receptor for the Epstein-Barr virus (EBV). Monoclonal antibodies B2, HB5, and B-ly4 belong to the CD21 cluster, recognizing different epitopes of the CD21-molecule. Immunohistology of lymphoid tissues employing these antibodies showed the known staining of B cells and dendritic reticulum cells. Surprisingly, B2, but not HB5 or B-ly4, stained a distinct spot in the cytoplasm of a major proportion of medullary thymocytes, in almost all peripheral blood lymphocytes, and in a substantial amount of cells in T-cell areas of peripheral lymphoid tissues. This distinct cytoplasmic B2 staining was confirmed by immuno-electronmicroscopy. A similar B2+ cytoplasmic dot was observed in B-lymphoblastic lymphomas. Staining of non-lymphoid tissues showed reactivity with all three CD21 mAb with epithelial cells of skin, lung, esophagus, jejunum, colon, pancreas, tonsil, adrenal cortex, renal tubuli, and parotid glands, and with hepatocytes and tongue muscle. In addition, endothelial cells of small vessels showed B2 staining. One possible explanation for our results is, that apart from the presence of B cells and follicular dendritic cells, a CD21-molecule may be expressed by other cell types. However, a maybe more likely explanation may be that the recognized epitopes are not exclusively associated with the C3d/EBV-receptor, but also with other structures. In particular should the possibility be recognized of cross-reactivity with CR2-related proteins, encoded by the large gene family, to which CR2 belongs.

Antibodies, Monoclonal↗

Haemopoiesis in human fetal and embryonic liver. Immunohistochemical determination in B5-fixed paraffin-embedded tissues.

Paraffin embedded tissue reactive monoclonal antibodies were used to study human embryonal and fetal haemopoiesis, combining optimal morphology with immunohistological determination of haemopoietic cell subtypes and their microenvironment. Seven embryonal and twelve fetal liver specimens were studied, having been fixed in B5-fixative and embedded in paraffin. The different haemopoietic lineages each showed their own immunophenotype and distribution; intercellular and microenvironmental relationships were easily determined. Erythroid cells are reactive with VIE-G4, LN1, and MT1, sometimes partly surrounding a central macrophage. Myelomonocytic cells react with LCA, MT1, MB3, LN2, and anti-lysozyme, and from 14 weeks onwards with LN3. Lymphoid cells show LCA, MT1, MT2, MB1, MB2, MB3, and LN2 reactivity. In a few cases some scarce My10+ early progenitor cells were seen. An important finding is the extensive MT1-reactivity distributed over all haemopoietic lineages, and the demonstration of immature haemopoietic blast cells exclusively expressing the MT1 antigen. Further studies employing MT1 are necessary to delineate the extent of the distribution and the possible function of the antigen. Use of the MT1 mAb may contribute to the elucidation of the exact nature of the haemopoietic blast cells and their place in haemopoietic development.

Antibodies, Monoclonal↗

Immaturity of the human splenic marginal zone in infancy. Possible contribution to the deficient infant immune response.

The immune response to polysaccharide Ag as present in the capsule of certain virulent bacteria has been demonstrated to be related to a functionally intact spleen. This immune response is almost completely defective in infancy. Because of this the development of cellular compartments in the human spleen was studied immunohistologically in frozen and paraffin tissue sections of 32 infant spleens (less than 2 y of age) and 6 spleens from children. Six cases of sudden infant death syndrome and 7 cases of infection or sepsis which were included showed no significant differences compared to the other cases. Whereas all other cellular compartments have completed their maturation to an adult-type immunophenotype and morphology within the first 5 mo, the infant marginal zone B cells show essentially different features compared to the adult situation. The main characteristics of the infant marginal zone B cells are the absence of CD21-(C3d/EBV-R) expression and the high percentage of cells strongly coexpressing IgM and IgD. As the marginal zone is supposed to be the site of the initiation of the immune response to polysaccharide Ag, there is a remarkable coincidence between the first appearance of MZ B cells with adult features, and the time of acquisition of the ability to mount an immune response to polysaccharides, including encapsulated bacteria.

Adolescent↗

Human marginal zone B cells are not an activated B cell subset: strong expression of CD21 as a putative mediator for rapid B cell activation.

In the human spleen the marginal zone (MZ) contains medium-sized B cells with a distinct immunophenotype. A main function attributed to the MZ is its involvement in the primary response to blood-borne antigens, in particular to thymus-independent antigens type 2. In this study the presence of antigens related to activation and proliferation was evaluated in human spleens by immunohistochemical staining. It appeared that MZ B cells do not show interleukin 2 receptor expression, and are in G0 phase of the cell cycle, as demonstrated by the lack of Ki-67 reactivity. The most interesting finding is the high CD21 expression by MZ B cells in the absence of IgD expression. As the CD21 antigen has been shown to be involved in B cell activation in close linkage with IgM, it can be suggested that MZ B cells are particularly well equipped for rapid and easy activation in a primary immune response.

Antigens, CD↗

Immunohistological analysis of human fetal lymph nodes.

A panel of monoclonal antibodies directed against various lymphoid and non-lymphoid cell subsets was used to study the lymph nodes of human fetuses of 16-40 weeks. B cells were of intermediate size and were present at all ages in primitive follicles and in the outer cortex. The fetal B-cell immunophenotype is indicative of an intermediate stage of development, just preceding the differentiation to mature B cell. Forty to sixty per cent Leu1+ B cells were observed in the follicles until the end of the second trimester. At all stages, T cells showed an immunophenotype similar to type III thymocytes, different from adult peripheral T cells, with a marked predominance of CD4+ T cells. Leu7+ NK cells were generally absent. OKIa+ interdigitating reticulum cells were present in T-cell areas. Some axillary lymph nodes showed strongly CD1+ dendritic cells, probably Langerhans' cells. Macrophages and granulocytes were present in varying numbers. Altogether, our results indicate that fetal lymph nodes are quite well differentiated at an early fetal age, although T and B cells do not (yet) show adult immunophenotypes. The expression of the CD38 antigen may be a main marker related to the immaturity of fetal T and B cells.

Antibodies, Monoclonal↗

In situ study of haemopoiesis in human fetal liver.

The anatomy of haemopoietic cells in human fetal liver was examined using immunohistological techniques on frozen sections of 31 fetuses (10-28 weeks gestational age). The immunohistological findings were consistent with reported cell suspension data. With regard to the location of haemopoietic activity no particular relationship existed between the various haemopoietic cell lineages. A large number of proliferating cells was present; only a few of these were reactive with haemopoietic progenitor cell monoclonal antibodies (MoAb) CD34. A population of haemopoietic cells expressed CD43 antigen (MoAb MT1) alone or together with anti-vimentin MoAb reactivity; this population needs further delineation. Erythropoiesis and myelopoiesis occurred in clusters around sinusoids and portal triad vessels respectively. Lack of MoAb reacting exclusively with early developmental stages of erythropoiesis and myelopoiesis precluded dissection of these lineages. Lymphopoiesis occurred in a loosely scattered pattern without any sign of focal development. Pre-B and B-cell numbers increased with gestational age. Cells expressing markers of more mature B cells (surface IgD, CD35, and CD21) were rare. Also, few cells reacted with mature T-cell markers, but CD7+ cells were obviously present. This expression of CD7 on haemopoietic fetal liver cells suggests that T-cell precursors develop in fetal liver as well as B cells.

Antibodies, Monoclonal↗

Immuno-architecture of human fetal lymphoid tissues.

Spleen, thymus and lymph node of human fetuses from the 12th to the 38rd week (spleen from 9 weeks) were investigated in an immunohistological study on B5-fixed paraffin embedded tissues, employing a panel of recently developed monoclonal antibodies, reactive with antigens resistant against fixation and paraffin embedment. The monoclonal antibodies included were MT1, MT2, MB1, MB2, MB3, LN1, LN2, LN3, LeuM1, Leu7, VIE-G4, together with polyclonal antibodies reactive with immunoglobulin heavy and light chains, and with lysozyme and S100-protein. The preservation of morphological detail together with immunoperoxidase staining of cellular subsets, allowed an accurate determination of the ontogenic development of the different cell types in situ, in relation to their micro-environment. The use of paraffin tissue reactive (monoclonal) antibodies gives an extra dimension to the study of fetal lymphoid tissues. This is of particular advantage in studies on very fragile tissues as in early embryonal and fetal ontogeny.

Antibodies, Monoclonal↗