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M R Parwaresch

Publications and source records attributed to M R Parwaresch.

At least 55 records · Page 3Linked to original sources

Induction of antigen expression of follicular dendritic cells in a monoblastic cell line. A contribution to its cellular origin.

Experiments were carried out to elucidate the cellular origin of the dendritic reticulum cell (DRC). The monoblastic cell line THP-1, the histiocytic cell line U-937, and the mononuclear cell fraction from peripheral blood (PMC) were stimulated with supernatants from lectin-stimulated peripheral blood lymphocytes and from stimulated T- and B-cell lines. Differentiation towards DRC was assessed by immunocytochemical demonstration of the DRC-specific antigen Ki-M4. Supernatants from isolated peripheral T lymphocytes and from T- and B-cell lines were capable of stimulating THP-1 to Ki-M4 antigen expression, whereas U-937 and the PMC fraction remained negative for this antigen throughout the experiments. These results provide further evidence for a relationship of DRCs with the mononuclear-phagocytic cell system and hence for their bone marrow origin. Furthermore, the data suggest that soluble factors of T and/or B cells are involved in mediating the differentiation process of precursor cells to DRC.

Antigens, Surface↗

Accessory cells in normal human and rodent lymph nodes: morphology, phenotype, and functional implications.

This chapter provides a brief review of the professional accessory cells present in normal human and rodent lymph nodes. When dealing with the function of accessory cells in the immune system it has to be borne in mind that in principle all cells may possess or acquire the capability of antigen presentation, which is the decisive initiating step in the specific host defense bound to the lymphoid cells. Professional accessory cells are arrayed at the afferent limb of the immune response. The majority of them have a typical dendritic morphology, so that the term "dendritic cells" is widely used instead of the term "accessory cells," and has replaced the traditional terms "reticulum cells" and "reticular cells." Professional accessory cells are characterized by: 1. The capability to stimulate specific T- or B-cell response following antigen pulsing 2. A dendritic morphology 3. Expression of major histocompatibility glycoproteins, complement, and Fc receptors as well as of various adhesion molecules. 4. Presentation of processed or unprocessed native antigens 5. Production and secretion of interleukin-1 and interleukin-6 The bimodal differentiation of lymphocytes seems to be reflected in the occurrence of two types of dendritic accessory cell: accessory cells involved in cellular (T accessory cells) and humoral (B accessory cells) immunity. T accessory cells of the lymph node comprise: 1. The lymphoid dendritic cell of Steinman, which probably represent a subset of blood monocytes with possible terminal differentiation into other T accessory cells 2. Veiled cells, which have been shown to represent Langerhans cells of the epidermal covering on their way to thymus-dependent areas of lymph node, probably giving rise to interdigitating dendritic (reticulum) cells 3. Interdigitating dendritic (reticulum) cells as the typical accessory cells of lymphoid T zone The T accessory cells share morphological, ultrastructural, immunophenotypic, and functional properties, are myeloid in origin, and very probably derive from monocyte lineage. As immune stimulatory cells they present processed antigen only and initiate T-cell proliferation and differentiation by interleukin-1 and -6 secretion. Accessory cells involved in the initiation of a primary humoral immune reaction have not been convincingly characterized. Accessory cells responsible for a secondary B-cell response, however, are the so-called follicular dendritic (reticulum) cells constituting the typical web-like structure of the primary and secondary lymphoid follicles. Unlike T accessory cells, follicular dendritic (reticulum) cells are distinguished by accentuated membrane desmosomes and extensive anastomosing branches of dendrites.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

M-CSF and M-CSF-receptor gene expression in acute myelomonocytic leukemias.

The role of hematopoietic growth factors in the pathogenesis of human leukemias is still obscure. In this study, RNA from 24 human acute myelomonocytic leukemias (AML) was used to analyze the expression of the macrophage colony stimulating factor (M-CSF) and its corresponding receptor (c-fms). Fifty percent of AML cells exhibited c-fms transcripts of regular length but at a lower level than in normal monocytes/macrophages. In most cases the reduced c-fms expression of AML cells was not associated with autostimulatory M-CSF expression. Only a few cases of AML showed co-expression of M-CSF and c-fms, which by contrast was regularly observed in cultivated blood monocytes and some tissue macrophage subsets. Higher levels of c-fms expression could be found in AMLs with a more mature monocytic immunophenotype. Permanent myelomonocytic cell lines expressed c-fms only after induction of monocytic differentiation. Neither the M-CSF gene nor the c-fms gene were rearranged in AML cells. In AML cells the homozygote genotype of the c-fms gene predominated. Our results do not provide evidence for the involvement of M-CSF and c-fms genes in human myeloid leukemogenesis. c-fms expression appears to indicate monocytic differentiation within the myelomonocytic lineage. We found autostimulatory M-CSF expression to be a physiologic feature of some tissue macrophages and hence not necessarily associated with neoplastic proliferation.

Adolescent↗

Proliferation, macrophage colony-stimulating factor, and macrophage colony-stimulating factor-receptor expression of alveolar macrophages in active sarcoidosis.

Alveolar macrophages (AM) in sarcoidosis display an enhanced mitotic activity. Immunocytochemical detection of the proliferation-associated Ki-67 antigen revealed significant increase in the number of proliferating AM in active sarcoidosis as compared with inactive stages of disease. Macrophage proliferation may provide an additional marker of disease activity. Since growth of macrophages is regulated by hematopoietic growth factors, we examined the expression of macrophage colony-stimulating factor (M-CSF), granulocyte M-CSF, and interleukin-3 by bronchoalveolar lavage cells in active sarcoidosis. Expression of granulocyte M-CSF or interleukin-3 genes could not be detected. AM in active sarcoidosis displayed M-CSF RNA to a comparable level like normal AM. They differed, however, in about 50% of cases analyzed, from normal AM by an enhanced level of c-fms proto-oncogene (M-CSF-receptor) expression. The enlarged proportion of proliferating AM in active sarcoidosis may be the result of an increased influx of strongly fms expressing macrophage precursors into the alveoli and autostimulation of macrophages by M-CSF.

Adult↗

[A new pan-macrophage antibody Ki-M1P stains plasmacytoid cells in paraffin sections of lymph nodes].

Plasmacytoid, T cells (PTC) occurring in cases of chronic non-specific lymphadenitis were investigated using a panel of monoclonal antibodies and cryostat sections. From the typical T cell antigens only CD4 was detectable on PTC. Antibodies directed against myelo-monocytic antigens such as Ki-M2, Ki-M6 (CD68), and Ki-M7 revealed positive reaction with these cells. The recently established monoclonal antibody Ki-M1P reactive with monocyte/macrophages shows a surface and granular cytoplasmic reactivity with PTC. This observation may indicate the myelo-monocytic origin. Ki-M1P detects a formalin resistant antigen and is thus applicable to conventionally processed paraffin sections as demonstrated in twenty cases of hystiocytic necrotizing lymphadenitis (KIKUCHI).

Antibodies, Monoclonal↗

[Clonality and stem cell defects in the molecular pathology of chronic myeloproliferative disorders].

The chronic myeloproliferative disorders (CMD) are characterized by sustained or progressive proliferations of bone marrow cells, affecting one or more lineages in varying combinations. They are classified in 4 subgroups but transitional forms and transformations among the different entities are common. Analysing RFLPs and methylation patterns of X-chromosomal genes we could show, that in each entity granulocytes as well as bone marrow cells are of monoclonal origin. These findings support the view that all forms of CMD have in common that they arise from a multipotent hematopoietic stem cell. CML can be differentiated from all other forms of CMD by the Philadelphia-chromosome which on the molecular level has been revealed as bcr-abl gene junction. We investigated 258 cases of CMD for rearrangement of the bcr gene and found that it selectively occurred in CML. The methods applied can be of diagnostic value in differentiating reactive from neoplastic proliferations by analysis of clonality, and in differentiation of CML from other types of CMD by detection of the bcr-rearrangement.

Bone Marrow↗

Distribution pattern of follicular dendritic cells in low grade B-cell lymphomas of the gastrointestinal tract immunostained by Ki-FDC1p: a new paraffin-resistant monoclonal antibody.

This study surveyed 97 cases of low grade B-cell lymphoma (LGBL) of the gastrointestinal tract (GIT) by conventional morphology and immunohistochemistry, focusing on the most frequent subtype: the so-called LGBL of the mucosa-associated lymphoid tissue (MALT). Special reference was made to the follicular dendritic cells (FDCs) selectively visualized by a new paraffin-resistant monoclonal antibody Ki-FDC1p. LGBL of the MALT accounted for 83 cases. The diagnosis was based on (a) a characteristic cytology, which included centrocytoid cells, a varying degree of plasma cell differentiation, and some blasts; (b) the presence of lymphoepithelial lesions; and (c) the occurrence of two types of follicles easily detectable with Ki-FDC1p. Some were restricted to the mucosa, contained normal germinal center cells, and were indistinguishable from reactive follicles. Others consisted of small clusters of FDCs, were randomly distributed throughout the tumor, and escaped detection in conventional stainings. Such small clusters of FDCs were found to be restricted to LGBL of the MALT, not occurring in other types of LGBL, and were interpreted as tumor-associated abortive follicles discernable from residues of reactive follicles due to their cellular constituents, localization, and distribution pattern. Eight cases showed closed sheets of blasts and were classified as high grade malignant lymphoma secondary to LGBL of the MALT. In two cases the LGBL of the MALT were restricted to the mucosa, in 31 cases the submucosa was also infiltrated, and in the remaining 50 cases the infiltration also involved deeper wall layers of the GIT.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

[Functional and morphological characterization of alveolar macrophages from patients with pulmonary sarcoidosis].

Bronchoalveolar lavage was performed in 28 patients with pulmonary sarcoidosis. Enzyme cytochemical staining with the tartrate-resistant acid phosphatase revealed a significantly increased portion of sarcoidosis macrophages showing a monocyte-like phenotype. Immunocytochemical staining with the proliferation-associated monoclonal antibody Ki-67 showed an increase of proliferating monocyte/macrophages related to disease activity in sarcoidosis. A functional activation of alveolar macrophages in sarcoidosis is indicated by spontaneous interleukin-1 secretion and increased release of oxygen free radical in sarcoidosis alveolar macrophages.

Bronchoalveolar Lavage Fluid↗

Liver findings in generalized mastocytosis. A clinicopathologic study.

Although the liver is one of the four organs most often involved in generalized mastocytosis (GM), little is known about macroscopic and microscopic liver findings in this rare disease. This study included 182 patients with GM (confirmed in most by bone marrow histologic study), comprising 52 cases of our own and 130 reported in the literature. Hepatomegaly was found in 131 (72%) of the 182 patients, cirrhosis in seven (4%), and periportal fibrosis in 25 (14%). Mast cell (MC) infiltration of the liver was confirmed histologically in 77 (42%). Liver specimens were available for further histologic investigation in 11 of our own cases of GM. Nine of these contained MC aggregates. Mast cells were found predominantly in the portal tracts but numerous MC also were loosely scattered throughout the sinusoids. Diagnostic confusion of GM with reactive lesions of the liver is unlikely to occur since MC, according to our own observations and the available literature, are found only in very low numbers in normal liver tissue, where they occur mainly in the portal tracts. Reliable identification of MC does, however, require special stains, like Giemsa, toluidine blue, or naphthol AS-D chloroacetate esterase.

Adult↗

Nodular paragranuloma can transform into high-grade malignant lymphoma of B type.

A follow-up study of 537 cases of Hodgkin's disease, lymphocyte predominance type, nodular--designated as nodular paragranuloma (NP)--found simultaneous presence of (n = 11) or subsequent transition into (n = 3) a large cell lymphoma (LCL) in 14 cases. Morphologically, the LCLs were classified in ten cases as centroblastic lymphoma (malignant lymphoma, diffuse, large cell, non-cleaved cell), in three cases as immunoblastic lymphoma (malignant lymphoma, large cell, immunoblastic), and in one case as large cell anaplastic lymphoma. Eleven of the 14 LCLs were studied immunohistologically. Five cases showed a monotypic immunoglobulin (Ig) pattern, seven were positive to the monoclonal B-cell marker Ki-B3, and three showed both monotypic Ig and Ki-B3 positivity. With anti-Ig and Ki-B3, nine of the 11 LCLs could be classified as B-cell non-Hodgkin's lymphoma. Only one case of LCL exhibited the typical phenotype of Hodgkin cells, ie, positivity to anti-CD15 (3C4) and anti-CD30 (Ber-H2). A retrospective follow-up study of these secondary LCLs of B type revealed a longer survival time than that of primary B-type LCLs and other secondary LCLs. These findings indicate that B-type LCL is the most common outcome when NP progresses into a lesion of higher malignancy and provide further evidence of a close relationship of NP to the B-cell system. They also suggest that it would be clinically relevant to distinguish between cases of B-type LCLs secondary to NP and cases of LCLs without association with NP. This implies that signs of a preexisting NP should be looked for when a B-type LCL is diagnosed.

Adolescent↗

[Phenotypic analysis and gene expression of inflammatory reaction forms of the monocyte/macrophage system].

The phenotypic heterogeneity of the monocyte/macrophage system is mirrored by the various inflammatory reactions of this cell system. Using monoclonal antibodies functional subpopulations of the monocyte/macrophage system can be observed, though the pathophysiological processes of the various inflammatory reactions still remain mostly unclear. By analysing phenotypic properties and gene expression in cells of the bronchoalveolar lavage it will be shown that the activity and the underlying pathophysiologic mechanisms of reactive processes can be defined.

Bronchoalveolar Lavage Fluid↗

Diversity of the human monocyte/macrophage system as detected by monoclonal antibodies.

Four monoclonal antibodies against the human monocyte/macrophage system, termed Ki-M1, Ki-M6, Ki-M7, and Ki-M8, are described with regard to their immunohistochemical tissue distribution pattern and their subcellular reactive sites. The differences found applying these analyses are also reflected by the various molecular weights of the recognized antigens. Based on these data it is proposed that the monocyte/macrophage system can be divided into the phagocytosing compartment on one hand and the immune accessory compartment on the other hand; the latter constitutes the interdigitating reticulum cells, the indeterminate dendritic cells, and the Langerhans cells, as well as the follicular dendritic cells (dendritic reticulum cells) as the accessory cells for T- and B-cell immune response, respectively.

Antibodies, Monoclonal↗

Modulation of c-fms proto-oncogene expression in human blood monocytes and macrophages.

The gene product of the c-fms proto-oncogene is a transmembrane protein with tyrosine-kinase activity that is obviously related to the receptor for the colony-stimulating-factor CSF-1. By Northern blot analysis, we investigated the expression of the cellular counterpart of v-fms in purified normal human blood mononuclear cells and different macrophage populations. The proto-oncogene c-fms expression was demonstrable in blood monocytes but not in blood lymphocytes. Short-term cultivated blood monocytes exhibited an increased expression of c-fms in comparison to freshly isolated blood monocytes, possibly due to a temporary down regulation of c-fms during the separation procedure of blood monocytes. A comparably high rate of fms-RNA expression was found in most of the analyzed samples of resident peritoneal macrophages, while resident alveolar macrophages showed a considerably lower level of c-fms expression. In this, alveolar macrophages resembled long-term cultivated adherent blood monocytes, which showed a down regulation of c-fms expression. By correlating these data obtained by Northern blot analysis with phenotypic properties of the analyzed monocyte/macrophage populations, it is concluded that different levels of c-fms expression in monocytes/macrophages correspond to their stage of differentiation and maturity.

Cell Differentiation↗

Decrease in LDL and increase in HDL concentrations in type II hyperlipoproteinaemic patients on low-dose combination therapy of cholestyramine and Complamin.

A low-dose combination of Complamin retard (1 g t.i.d.) and cholestyramine (4 g b.i.d.) was compared with each agent alone in 2 serial open trials without dietary restriction using type IIa and IIb hyperlipoproteinaemic patients. Complamin alone produced decreases in LDL and VLDL cholesterol concentrations (up to 20%) whereas cholestyramine alone produced only a modest reduction in LDL (up to 15%). The combination produced marked, progressive reductions in total cholesterol (up to 35%) and LDL (up to 40%); reductions in VLDL (up to 45%), total triglyceride (up to 60%) and free fatty acids (up to 60%) were found only in type IIb patients. The average increase in HDL-cholesterol from the 2 studies for combination therapy was 35%. No side-effects were reported or measured and compliance was excellent. The results demonstrate the potential of a method of achieving beneficial actions on lipoprotein levels with a well-tolerated therapy.

Adult↗

Monoclonal antibodies Ki-B3 and Leu-M1 discriminate giant cells of infectious mononucleosis and of Hodgkin's disease.

In infectious mononucleosis (IM), the involved lymphatic tissue may contain large blasts which are generally referred to as Hodgkin cell-like cells when mononuclear and as Sternberg-Reed cell-like cells when multinuclear. The resemblance of these reactive cells to true Hodgkin and Sternberg-Reed cells constitutes a major differential diagnostic problem. In this paper, we report a study of 20 cases of Hodgkin's disease (HD); five of nodular sclerosis and 15 of mixed cellularity type) and of 20 clinically and serologically confirmed cases of IM with the aim of developing immunohistologic criteria for their reliable differentiation. Routinely processed paraffin sections were subjected to the immunoperoxidase reaction using the monoclonal antibodies Leu-M1 (anti-CD15) and Ki-B3. The subcellular distribution of the immunoreactivity to Ki-B3 was controlled at the electron microscopic level. In all cases of HD, many Hodgkin and Sternberg-Reed cells were found to be positive for Leu-M1, whereas the same cells were invariably negative for Ki-B3. By contrast, cells similar to Hodgkin and Sternberg-Reed cells in IM were consistently negative for Leu-M1. The majority of these cells reacted positively for Ki-B3. The results imply that immunohistochemical application of these two antibodies facilitates a clear-cut discrimination of true Hodgkin and Sternberg-Reed cells from similar cells of IM.

Adolescent↗

Immunoelectronmicroscopic investigation of Hodgkin's disease with monoclonal antibodies against histiocytes.

8 cases of Hodgkin's disease (HD nodular sclerosis (n = 3), HD mixed type (n = 2), and nodular paragranuloma (n = 3] were investigated with monoclonal antibodies against histiocytes (Ki-M1, Ki-M3, Ki-M4, Ki-M6, and Ki-M7). Reactivity of H- and SR-cells with the monoclonal antibodies Ki-M3 and Ki-M7 could be shown at the ultrastructural level in cases of HD of nodular sclerosis and mixed type. In nodular paragranuloma no positive H-, SR- nor L & H-cells could be demonstrated. The reaction site of the monoclonal antibodies in H- and SR-cells was comparable to those in histiocytes.

Aged↗