Search PubMed⌕ Search

Biomedical subjects

S Poppema

Publications and source records attributed to S Poppema.

At least 127 records · Page 7Linked to original sources

Simultaneous standard light microscopy and immunohistology on bronchoscopically procured lung cancer specimens.

A method is described which enables the routine assessment of in situ phenotypic differences in lung cancer specimens. In this method, bronchoscopically procured biopsies are mildly fixated and split into two parts. One part is processed according to standard histological procedures, ensuring optimal morphology for normal pathological evaluation of the case. The other part is used for monoclonal antibody based immunohistology. The reactivity of a panel of monoclonal antibodies directed against different lung cancer and human leucocyte associated antigens has been assessed. It is shown that antigens that are normally destroyed during routine fixation and embedding technology are still reactive in the procedure. It is concluded that the procedure enables a study of monoclonal antibody defined phenotypic features, without interfering with the normal histopathological evaluation of the case.

Antibodies, Monoclonal↗

Acute rejection in human liver grafts: a comparative histologic study of cases maintained on azathioprine and prednisone versus cyclosporine A and low-dose steroids.

The morphology of acute rejection (AR) in biopsies of liver allografts obtained in the first 2 weeks after transplantation was analyzed. Material from patients maintained on azathioprine and prednisone (AZA; Groningen, The Netherlands) was compared with that of patients receiving cyclosporine A and prednisone (with or without azathioprine) in low doses (CSA; Minneapolis). Strict selection criteria were applied to exclude circulatory and biliary complications and viral infection in this early observation period after transplantation. Follow-up biopsies ranged from 3 weeks to 1 year after transplantation. Time zero biopsies and/or pretransplant biopsies served as baseline histology, Our data revealed an identical morphologic picture during AR early after transplantation in both patient groups, except for a more marked degree of venous endothelialitis and hepatocyte ballooning in the Minnesota material. The follow-up biopsies suggested a spontaneous resolution of these early rejection episodes without antirejection treatment in six of the ten AZA patients. No differences in the long-term survival rate between the CSA- and AZA-treated patients were observed.

Acute Disease↗

Immunophenotypes of malignant lymphoma centroblastic-centrocytic and malignant lymphoma centrocytic: an immunohistologic study indicating a derivation from different stages of B cell differentiation.

Five cases of intermediate lymphocytic lymphoma (ILL), 13 cases of malignant lymphoma centrocytic (MLCC), and 27 cases of malignant lymphoma centroblastic centrocytic (MLCBCC) were studied morphologically and with the aid of a panel of monoclonal antibodies. The immunophenotypes of ILL and MLCC (IgM+/IgD+, MT1+, CALLA-) indicate a mantle zone or very early follicle center derivation. The immunophenotypes of MLCBCC (IgM+ or IgG/IgA+, MT1-, CALLA+) indicate a "true" follicle center derivation. The morphologic diversity of MLCBCC could not be related to specific immunophenotypes.

Adult↗

Pre-B-cell non-Hodgkin's lymphoma in childhood. Report of a case and review of the literature.

The authors studied a six-year-old girl with a cervical lymphoblastic lymphoma. Initial blood study results were within normal ranges, and no evidence of leukemia was found. Immunophenotype analysis of this lymphoma was consistent with a pre-B-cell non-Hodgkin's lymphoma. Other notable histopathologic findings were the fascicular growth pattern of the tumor and the very convoluted nuclei of the lymphoblasts. At present, only few cases of this rare immunophenotype of non-Hodgkin's lymphoma have been reported in children. A panel of monoclonal antibodies is suggested to be applied on frozen tissue sections in order to establish a precise diagnosis in childhood non-Hodgkin's lymphomas, which should ultimately have therapeutic and prognostic impact.

Antigens, Differentiation↗

Detection of small cell lung cancer metastases in bone marrow aspirates using monoclonal antibody directed against neuroendocrine differentiation antigen.

To detect metastases in the bone marrow of patients with small cell lung cancer, immunofluorescence with a monoclonal antibody detecting a membrane antigen (MOC-1) associated with small cell lung cancer was performed on 53 bone marrow aspirates from 30 patients. In 19 (63%) patients MOC-1 reactive cells were detected. Simultaneous histopathological examination of the bone marrow biopsy specimens detected tumour cells in only six (20%). The method is more sensitive than conventional histochemical staining of bone marrow aspirate and may eventually be able to show additional subgroups, such as patients with limited disease who might benefit from adjuvant radiotherapy or surgery.

Antibodies, Monoclonal↗

Immunohistochemical antigen demonstration in plastic-embedded lymphoid tissue.

We describe a method for post-embedding immunohistochemical demonstration of a wide range of antigens in glycol methacrylate-embedded tissue. Rat spleen and thymus tissues were fixed by immersion in fixatives containing different concentrations of paraformaldehyde, washed in sucrose phosphate buffer, dehydrated in acetone, infiltrated in a glycol methacrylate mixture in which the commonly used softener 2-butoxyethanol was replaced by butaandiol monoacrylate, and embedded. Trypsin was used to re-expose the masked antigenicity. Excellent results were obtained with a panel of monoclonal antibodies (MoAbs) directed against T-cells, B-cells, Ia-positive cells, macrophages, follicular dendritic cells, and leucocyte common antigen-bearing cells. The method described combines exact localization of antigens with optimal tissue morphology.

Acrylates↗

Early induction of MHC antigens in human liver grafts. An immunohistologic study.

The present study documents major histocompatibility complex (MHC) Class I and II expression during early acute rejection of human liver grafts. Serial graft biopsies (pretransplant, time zero, and 1 week) were studied. Ten patients received azathioprine (AZA) and prednisone; the other six patients were treated with quadruple therapy (azathioprine, cyclosporine A, prednisone, and cyclophosphamide). To study the specificity of changes in MHC antigen expression, biopsies of six patients with minor or no morphologic abnormalities served as controls. In addition, phenotypes of inflammatory cells present during rejection were analyzed using a panel of monoclonal antibodies. The results show that during acute rejection expression of MHC Class I and II antigens increased significantly in the AZA-treated patients, in a pattern similar to that seen in the patients treated with quadruple therapy, showing enhanced MHC Class I expression on hepatocytes, bile duct epithelium, and sinusoidal endothelium, and Class II antigen on Kupffer cells and sinusoidal endothelium. Bile duct epithelium was consistently positive for Class II antigen; no significant difference with the nonrejection group was observed. T cells are the predominant inflammatory cells during rejection with equal quantities of CD4+ and CD8+ cells. A majority of the infiltrating T cells show expression of Class II antigen but do not react with anti-interleukin-2 receptor antibody. This may be the result of immunosuppressive therapy or a simple reflection of the temporary expression of interleukin-2 receptors during lymphocyte activation. The authors hypothesize that the induction of MHC antigens on bile duct epithelium leads to rejection whereas the expression on hepatocytes represents an epiphenomenon.

Adolescent↗

B lymphocyte differentiation in the rat: production and characterization of monoclonal antibodies to B lineage-associated antigens.

Three mouse monoclonal antibodies (mAb) directed against rat B lineage antigens were produced. The mAb, designated HIS14 (IgG1), HIS22 (IgM) and HIS24 (IgG2b), were characterized for binding to lymphoid and nonlymphoid tissues by immunoperoxidase staining of frozen sections and by (double-) immunofluorescence staining of single cell suspensions from lymphoid organs. HIS14 recognized a pan B cell determinant: it reacted with virtually all cells of each anatomic B cell compartment and with about 95% of surface (s)Ig+ cells in thoracic duct lymph and in suspensions of spleen and lymph nodes. HIS22 and HIS24 detected B lineage-associated antigens expressed by major subpopulations of B cells. HIS22 predominantly stained the lymphocyte corona, but not (or weakly) the germinal centers and splenic marginal zones, whereas HIS24 reacted with both corona and germinal center and not (or weakly) with marginal zone. In accordance with this, substantial proportions of sIg+ cells in spleen cell suspensions did not express HIS22 or HIS24 determinants (20% and 27%, respectively). In bone marrow the vast majority of cytomplasmic mu+ pre-B cells were HIS14+ and HIS24+, and up to one third also HIS22+, indicating an appearance of the determinants early in B lymphocytopoiesis. The antigens recognized by HIS14, HIS22 and HIS24 are lost during the final stage of B cell differentiation: none of the mAb bound to plasma cells. As far as detectable, neither cells of myeloid and erythroid lineages in bone marrow nor thymocytes were stained by HIS14, HIS22, or HIS24. In suspensions of peripheral lymphoid organs (spleen and lymph nodes) but not in thoracic duct lymph, HIS14 and HIS24 labeled a small proportion (12% and 14%, respectively) of Ig- cells. HIS22 did not bind to Ig- peripheral lymphocytes. Reactivity of HIS14, HIS22 and HIS24 with nonlymphoid tissues was virtually absent; HIS22 stained the high endothelial venules in lymph nodes and Peyer's patches. As determined by immunoblotting, the antigenic determinants on lymph node cells recognized by HIS14, HIS22 and HIS24 were present on molecules with an apparent molecular mass of 205 kDa, 210 (and 175) kDa and 205 kDa, respectively, which is similar to the molecular mass of the B cell form of the rat leukocyte common antigen. In addition, the antigens recognized by HIS14, HIS22 and HIS24 co-capped with the leukocyte common antigen. This suggests that each of the three mAb recognize determinants present on the B cell form of the leukocyte common antigen.

Animals↗

Lymphocyte subpopulations in peripheral blood and bone marrow in patients with idiopathic myelofibrosis.

In 8 patients with idiopathic myelofibrosis (IM) T and B cells were studied in view of the possibility that immunological dysfunctions are involved in initiating or contributing to the bone marrow fibrosis. In peripheral blood the absolute numbers of E-SRBC and OKT3+ lymphocytes were significantly reduced; in addition a significant decline was observed in the proportion and absolute numbers of OKT8+ cells, resulting in a reversed Leu-3a/OKT8 ratio. An impaired B cell function was observed in 4 of the 8 patients, characterized by a disturbed in vitro pokeweed mitogen stimulated immunoglobulin synthesis and low serum immunoglobulin levels. Immuno-histological studies of the bone marrow demonstrated a scarcity of T cells but normal numbers of B cells. However, no correlation was noted between the observed deviations of B and T cells and the degree of bone marrow fibrosis determined by means of bone marrow histology and serum procollagen-III levels. These data are not sufficient to support the hypothesis that immunological changes in IM are primarily involved in the process of bone marrow fibrosis.

Adult↗

Expression of major histocompatibility complex antigens and replacement of donor cells by recipient ones in human liver grafts.

The disappearance of certain cell populations of donor origin and their replacement by recipient-specific cells constitutes a possible explanation for the relatively mild course of acute rejection despite lack of MHC compatibility in human orthotopic liver transplantation (OLT). In the present report, graft biopsies of 12 OLT patients from a total of 42 patients were studied for expression of MHC antigens after transplantation using monoclonal antibodies to HLA-ABC and HLA-DR. The patients were selected based upon donor-recipient mismatching for HLA-A2, B7, Drw52, or DQw1. Monoclonal antibodies to these 4 polymorphic HLA antigens and monoclonal antibodies to HLA-ABC and -DR were applied to frozen tissue sections and visualized using an immunoperoxidase technique. Expression of HLA-ABC and -DR on, respectively, hepatocytes and bile duct epithelium were observed in posttransplant graft conditions such as viral infections, cholangitis, and acute rejection. However, no specific pattern of MHC antigen distribution was observed for these various pathological graft conditions. Disappearance of DR-positive Kupffer cells of donor origin and immigration of recipient ones was encountered in the early posttransplant biopsies. This Kupffer cell replacement coincided with a reversible episode of acute rejection. The disappearance of highly immunogenic cellular components as HLA-DR positive Kupffer cells of graft origin may be one of the mechanisms contributing to the mild rejection response observed in human liver transplantation.

Antibodies, Monoclonal↗

Experimental gingivitis in a Down's syndrome child and sibling.

Biopsies were taken from a child with Down's syndrome and her sibling under experimental gingivitis conditions and analyzed with monoclonal antibodies. At first, plaque caused a shift from a predominance of T cells to a predominance of B cells. Later, a gradual increase of T cells and a looser arrangement of B cells were observed.

B-Lymphocytes↗

Expression of class II major histocompatibility complex antigens on alveolar epithelium in interstitial lung disease: relevance to pathogenesis of idiopathic pulmonary fibrosis.

To determine whether expression of class II major histocompatibility complex antigens on alveolar epithelium is relevant to the pathogenesis of idiopathic pulmonary fibrosis (IPF) lung biopsy specimens were investigated from nine patients with IPF with or without connective tissue disease, four patients with sarcoidosis, eight patients with lung disease of presumably infectious origin, and five controls. The alveolar epithelium stained strongly with anti-Ia (HLA-DR) or Leu 10 (HLA-DS) monoclonal antibodies, in eight of nine biopsy specimens from patients with IPF, in three of four biopsy specimens from patients with sarcoidosis, in all six biopsy specimens from patients with presumably viral, mycobacterial, or pneumocystic lung disease, but not in control lung tissue, nor in two biopsy specimens from patients with bacterial pneumonia. Mononuclear cell infiltrates consisted of T4 positive (helper/inducer) lymphocytes, predominantly present in a nodular arrangement in the interstitium, and T8 positive (cytotoxic/suppressor) cells, distributed equally in the interstitium and subepithelially or intraepithelially. T8 cells outnumbered T4 cells in six of nine biopsy specimens from patients with IPF, but in none of the biopsy specimens from patients with sarcoidosis or interstitial lung disease of infectious origin. Although the expression of class II antigens on the alveolar epithelium which is infiltrated by T8 cells in IPF is consistent with local presentation of autoantigens and an ensuing local immune response, class II expression is also present in interstitial lung disease of sarcoidosis and microbial infections: its role in the pathogenesis of IPF must therefore remain speculative.

Adolescent↗

Intermediate filament expression in small cell lung cancer; poor correlation to in vitro data.

A panel of monoclonal antibodies, detecting different intermediate sized filament proteins, was prospectively applied on all specimens derived from S.C.L.C. patients attending our clinic in 1985. Reactivity with the antibodies was subsequently correlated to clinical data. The results indicate a heterogeneous pattern of reactivity of the assessed antibodies. However this heterogeneity is not a straightforward extension of the intermediate sized filament expression in SCLC cell lines.

Antibodies, Monoclonal↗

Fetal and neonatal development of human spleen: an immunohistological study.

Localization and immunophenotype of lymphocyte subsets in fetal human spleens were studied by employing a panel of monoclonal antibodies (McAb) in an immunoperoxidase staining procedure on frozen tissue sections. Spleens varied from 15 weeks of gestational age (gestational weeks, gw) to newborn. The white pulp consisted of intermediate-sized lymphocytes; no separate compartments could be discerned. Germinal centre development was not observed. Dendritic cells stained for B2, HB5, aC3bR, anti-DRC and OKIa, but in most cases not for immunoglobulin. Although low cellular immunity is observed in neonates, T cells showed adult phenotypes in proportions comparable to the adult situation; immature OKT6(+) lymphocytes were rarely seen. Very few cells stained with anti-NK cell antibody Leu7. B cells all expressed B1, Leu14, aC3bR, T10 and OKIa, were strongly positive for BA1, and mostly stained very weakly for B2 and HB5. Almost all B cells expressed IgM and IgD simultaneously, and very few expressed IgG. IgA-positive cells were absent. At 15 gw a considerable number of IgM(+) B cells showed Leu1 staining, but this decreased during development. These cells may represent the normal counterpart of Leu1(+) IgM(+) cells observed in B-CLL and immunocytic and centrocytic malignant lymphomas. After 25 gw only very few Leu1(+) IgM(+) cells were seen. Altogether, the morphology and immunophenotype of white pulp B cells were different from the predominating adult B-cell subsets, at least until birth. These 'immature' splenic B cells may be precursors for adult splenic B-cell subsets. Considering the presumed role of the marginal zone in the immunity against TI-2 antigens, the absence of a marginal zone at birth may be a main factor in the defective immunity against these antigens in neonates.

B-Lymphocytes↗

Monoclonal antibodies (MT1, MT2, MB1, MB2, MB3) reactive with leukocyte subsets in paraffin-embedded tissue sections.

The absence of reactivity on routinely prepared tissue sections has hampered the use of monoclonal antileukocyte antibodies in diagnostic histopathology. Here we describe five new antibodies reactive with leukocyte subsets in formaldehyde-fixed, paraffin-embedded tissue sections. Antibody MT1 is reactive with mature and immature T cells and not with mature B cells. MT2 is reactive with mature T cells and B cells, but not with immature T cells, activated T cells, and germinal center B cells. Antibody MB1 is reactive with all B cells, with about 50% of mature T cells, and not with immature T cells. MB2 is reactive with all B cells and not with T cells. However, MB2 also stains endothelial cells and several types of epithelial cells. MB3 is reactive with B cells and histiocytes, but not with T cells. The antibodies were tested on a series of lymphomas that were also immunophenotyped with a panel of well-established reagents on frozen tissue sections. The results indicate that the MB and MT antibodies are useful tools in the study of reactive and neoplastic disorders of the lymphoid system.

Antibodies, Monoclonal↗

Clonal immunoglobulin gene rearrangements in tissues involved by Hodgkin's disease.

The nature of Reed-Sternberg cells, the abnormal cells of Hodgkin's disease, is controversial. Morphological and immunologic marker studies suggested different cells of origin. To investigate a possible B or T cell origin, immunoglobulin and T cell receptor gene analyses were performed on tissues from 11 patients in early and late stages of Hodgkin's disease. In addition, the immunologic marker patterns of the Reed-Sternberg cells were determined. Rearrangements of immunoglobulin heavy- and light-chain genes were detected in tissues from five patients, particularly in late stages of the disease when lymphocyte depletion had occurred. No rearrangements of T cell receptor genes were found. The results indicate that clonal immunoglobulin gene rearrangements can be detected in tissues involved by Hodgkin's disease.

Adolescent↗

Expression of class II MHC antigens on alveolar epithelium in fibrosing alveolitis.

Lung biopsy specimens from eight patients with fibrosing alveolitis with or without connective tissue disease were investigated for the presence of immune deposits and the expression of class II histocompatibility antigens on the alveolar epithelium. Immune deposits were not detected. The alveolar epithelium stained strongly with anti-Ia (HLA-DR) monoclonal antibodies in seven out of eight biopsy specimens from the patients, but not in control lung tissue. Sub- and intra-epithelially localized mononuclear cell infiltrates consisted predominantly of T8-positive (cytotoxic/suppressor) lymphocytes. The expression of class II antigens on the alveolar epithelium and its infiltration with T8 positive cells is consistent with local presentation of self-antigens and an ensuing local immune response.

Adult↗