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Biomedical subjects

S Poppema

Publications and source records attributed to S Poppema.

At least 109 records · Page 6Linked to original sources

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↗

Progressive renal failure due to renal invasion and parenchymal destruction by adult T-cell lymphoma.

A 43-year-old patient of occult adult T-cell lymphoma (ATL) presenting with systemic illness and progressive renal failure due to lymphomatous infiltration of kidneys is described. The striking feature observed was destructive infiltration of the kidneys, by malignant CD4 cells, virtually replacing the normal renal architecture. The diagnosis of lymphoma was made by renal biopsy. Clinical features typical of ATL were hypercalcemia, lytic bone lesions, and profound wasting and inanition. The patient died rapidly despite attempted therapy. The case illustrates the potential of ATL for direct renal parenchymal destruction.

Adult↗

Induction of B-cell chronic lymphocytic leukaemia and hairy cell leukaemia like phenotypes by phorbol ester treatment of normal peripheral blood B-cells.

To investigate the relationship between normal B-cells, B-cell chronic lymphocytic leukaemia (B-CLL) cells and hairy cell leukaemia (HCL) cells the three cell types were incubated with phorbol myristic acetate (PMA). The parameters studied were morphology, immunophenotype and tartrate resistant acid phosphatase (TRAP). PMA stimulation of B-cells induced morphological changes as well as CD5, CD11c, B-ly 7 and TRAP positivity. The cells formed small aggregates, the cell membranes were ruffled and frequently hairy and a small number of cells became plastic adherent and developed dendritic structure. CD5 and CD11c appeared on day 2, imitating a B-CLL phenotype. On day 3 and 4 a decrease of CD5, an increase of CD11c and the appearance of B-ly 7 could be seen mimicking an HCL phenotype. The changes in B-CLL and HCL upon PMA stimulation were mainly morphological: the B-CLL cells became ruffled and aggregated strongly, while the HCL cells developed dendritic features and became adherent. The immunophenotype of the PMA stimulated HCL cells did not change. The B-CLL cells remained CD5 positive and did not become B-ly 7 positive. The findings indicate that although PMA stimulation of normal peripheral blood cells results in CLL- as well as HCL-like phenotypes, similar stimulation of B-CLL cells does not result in an HCL-like phenotype.

B-Lymphocytes↗

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↗

T-lymphoblastic and peripheral T-cell lymphomas in the northern part of The Netherlands. An immunologic study of 29 cases.

The morphologic type, immunophenotypes, and clinical presentation of 12 cases of T-lymphoblastic lymphoma and 17 cases of peripheral T-cell lymphoma were studied. The lymphoblastic cases were subclassified according to intrathymic stages of T-cell differentiation. Two cases had an early intrathymic immunophenotype (CD4-negative, CD8-negative, CD1-negative), seven cases had an intermediate intrathymic immunophenotype (CD1-positive, CD4-positive, CD8-positive), and two cases had a late intrathymic immunophenotype (CD1-positive, CD8-positive, CD4-negative); one case expressed T-cell and B-cell markers. The peripheral T-cell lymphomas were morphologically subclassified according to the updated Kiel classification. T-cell lymphomas of low-grade malignancy--chronic lymphocytic lymphoma, T-zone lymphoma, and pleomorphic small cell lymphoma--in general had a complete immunophenotype matching the immunophenotypes of normal peripheral T-cells. In addition these cases were CD38-positive and HLA class II-positive. The T-cell lymphomas of high-grade intermediate and large cell, immunoblastic and large cell anaplastic lymphoma--were characterized by loss of T-cell markers. For their establishment as T-cell lymphoma a panel of monoclonal antibodies is needed.

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↗

Sjögren's syndrome with specific cutaneous manifestations and multifocal clonal T-cell populations progressing to a cutaneous pleomorphic T-cell lymphoma.

A case is presented of primary Sjögren's syndrome of the parotid gland with specific skin manifestations, consisting of diffuse lymphoid infiltrates with proliferative and metaplastic changes of sweat glands, a histologic picture similar to that seen in the parotid gland. Material of the parotid gland, a submandibular lymph node showing expanded T-cell areas, and several skin biopsies were studied immunohistologically for the presence of clonal B-cell populations. Because of a polyclonal kappa/lambda pattern of the B-lymphocytes, the possibility of a B-cell non-Hodgkin's lymphoma (NHL) was excluded. The initially morphologically benign lymphocytic skin infiltrates (1985) changed into a pleomorphic T-cell lymphoma (1987). Southern blot analysis of the atypical skin infiltrates and of the original material of the parotid gland and submandibular lymph node revealed identical clonal rearrangements of the T-cell receptor B-chain. Rearrangement of Ig genes was not found.

Aged↗

Transition in CD45 isoform expression during differentiation of normal and abnormal B cells.

We have demonstrated a transition in the expression of CD45 isoforms, from the expression of the high molecular weight CD45R to the low molecular weight CD45 p180 isoform on normal and on monoclonal (possibly malignant) B cells undergoing differentiation into plasma cells. The differentiation into plasma cells was shown by the loss of CD20 and CD21 surface antigens, a reduced expression, but in our system not a complete loss, of CD19, and the expression of the plasma cell marker PCA-1. We used three-color immunofluorescence to demonstrate the shift from CD45R to CD45 p180 on CD19+CD20-CD21- cells in cultures of normal cells stimulated by pokeweed mitogen (PWM). Furthermore, tissue sections of extramedullary plasmacytomas, where plasma cells were defined by morphology and expression of cytoplasmic Ig, showed a complete loss of CD45R and CD45 p180 antigens, although the cells retained expression of CD45 common determinants. Finally, we have analysed PBMC from patients with Waldenström's macroglobulinemia (WM) at various stages of disease, and demonstrated that the monoclonal B cell subset present in their peripheral blood is heterogeneous in the expression of CD45 isoforms, including cells bearing only CD45R, those with a transitional CD45R+CD45 p180+ phenotype, and those expressing only CD45 p180. Upon stimulation in vitro these cells show greatly increased expression of CD45 p180. The differential expression of CD45 isoforms within a clonal B cell subset in the blood of these patients suggests that the monoclonal B cells in WM represent a continuously differentiating lineage of CD45R+ mature B cells giving rise to CD45 p180+ pre-plasma cells.(ABSTRACT TRUNCATED AT 250 WORDS)

Antigens, Differentiation↗

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↗

Clinical characterization of non-small-cell lung cancer tumors showing neuroendocrine differentiation features.

In most cases of small-cell lung carcinomas (SCLC) phenotypic features compatible with a neuroendocrine differentiation status can be identified by monoclonal (MOC) antibody-based immunohistological procedures. Similar features can be recognized only in a minority of non-SCLC tumors. During a period of 30 months, all diagnostic non-SCLC biopsies (141 cases) were prospectively analysed for the presence of markers indicative for neuroendocrine differentiation. In 31% of all cases, such a presence could be noticed. Neuroendocrine differentiation (50% to 100% positive-staining tumor cells) was recognized more frequently in adenocarcinoma when compared to large-cell and squamous-cell carcinoma (chi 2 = 9.31, 2 degrees of freedom, P less than 0.01). To investigate whether the clinical behavior of these "neuroendocrine" non-SCLC cases mimics SCLC, a multivariate analysis for prognostic factors was performed. Among other prognostic factors, biopsies containing more than 50% positive-staining tumor cells with the MOC antibody-1 (MOC-1) were recognized as negative prognostic factors.

Antibodies, Monoclonal↗

Monoclonal antibodies reactive with hairy cell leukemia.

Monoclonal antibodies reactive with hairy cell leukemia were developed to aid in the diagnosis of this subtype of B cell chronic lymphocytic leukemia and to gain better insight into the origin of hairy cells. Three antibodies were found to be of value in the diagnosis of hairy cell leukemia. Antibody B-ly 2 can be considered a pan-B cell reagent and generally reacts similar to CD22 antibodies. Antibody B-ly 6 is reactive with the same antigen as CD11c (p150/95), an antigen that is present on hairy cell leukemia, macrophages, and a minor subpopulation of lymphocytes. Antibody B-ly 7 is a unique antibody reactive with 144 Kd antigen present only on hairy cell leukemia and a very small population of normal B lymphocytes. This subpopulation may be the counterpart of hairy cells.

Antibodies, Monoclonal↗

The nature of the lymphocytes surrounding Reed-Sternberg cells in nodular lymphocyte predominance and in other types of Hodgkin's disease.

The lymphocytes surrounding Reed-Sternberg cells may play an important role in the pathogenesis of Hodgkin's disease. In this study, T cells in different subtypes of Hodgkin's disease were analyzed in situ by an immunoperoxidase method employing a panel of antibodies, including several paraffin tissue-reactive monoclonal antibodies. The T cells in Hodgkin's disease-involved tissues were found to be activated CD4-positive T cells that are UCHL1+ and CD45R-. This immunophenotype is compatible with an activated helper-inducer memory T cell population. The T cells in the nodular lymphocyte predominance subtype were found to have additional positivity for Leu 7, indicating a subpopulation of CD4+ T cells, normally confined to the light zone of germinal centers of secondary follicles.

Adult↗

Characterization of three small cell lung cancer cell lines established from one patient during longitudinal follow-up.

Three classic-type, small cell lung cancer cell lines (GLC-14, GLC-16, and GLC-19) have been established from one patient during longitudinal follow-up. During this period the tumor changed from sensitive to completely resistant to (chemo)therapy. A phenotypical and functional characterization of the different cell lines is given in combination with the matching clinical data. (a) The cell lines have been compared with the biopsies from which they were derived. There was a good match between the morphological, biochemical, and immunohistological findings in the cell lines as compared to those obtained in the biopsies. When the biopsy and cell line (GLC-14) obtained before the start of therapy were compared to the biopsies and cell lines (GLC-16 and GLC-19) acquired after the first and second reinduction therapy, respectively, no major changes could be observed. The only clear alteration was the loss of a neuroendocrine antigen (defined by monoclonal antibody MOC-51) in the posttherapy specimens. (b) The doxorubicin, melphalan, and etoposide sensitivity in vitro reflected the clinically observed development of resistance to treatment. The cell line (GLC-14) established before the start of therapy was more sensitive than the lines (GLC-16 and GLC-19) obtained after treatment. It is concluded that the cell lines described in this paper represent a well-characterized in vitro model in which the development of drug resistance in small cell lung cancer can be studied.

Antigens, Differentiation↗

Spontaneous regression of a small non-cleaved cell malignant lymphoma (non-Burkitt's lymphoblastic lymphoma). Morphologic, immunohistological, and immunoglobulin gene analysis.

Complete spontaneous regression of high-grade malignant non-Hodgkin's lymphoma is extremely unusual. In this report the authors describe a complete spontaneous remission after surgical excisional biopsy of a small noncleaved cell malignant lymphoma (non-Burkitt's lymphoblastic lymphoma) of the tonsil in a 12-year-old boy. The diagnosis was confirmed by immunohistologic and immunoglobulin gene analysis. Similar studies were performed on the cervical lymph node excised 2 weeks later when spontaneous remission had occurred. The patient has remained in good health for over 3 years.

Adolescent↗

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↗