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M R Parwaresch

Publications and source records attributed to M R Parwaresch.

At least 37 records · Page 2Linked to original sources
PubMed1992

Lymph node findings in generalized mastocytosis.

Lymph nodes from 21 cases of generalized mastocytosis were studied histologically to confirm or exclude mast cell infiltration, and to investigate their micro-architecture. Mast cell infiltrates were detected in 17 (80%) of the lymph nodes and were found mainly in the medullary cords and sinuses. Diffuse infiltration was seen in 14 cases and focal infiltration in three cases. The following pathological findings were frequently observed: germinal centre hyperplasia (n = 14), which is probably a nonspecific finding; and hyperplasia of small blood vessels, which sometimes resembled high endothelial venules (14), eosinophilia (8), plasmacytosis (7) and collagen fibrosis (6), all of which may well be related to the effects of mediators released by mast cells. Infiltrates of acute or chronic myeloid leukaemia were seen in six lymph nodes. Division of the cases into two prognostically different groups, i.e. systemic mastocytosis, in which the skin lesions of urticaria pigmentosa are present and the prognosis is favourable, and malignant mastocytosis, in which there is no cutaneous involvement and the prognosis is poor, revealed that all six lymph nodes exhibiting leukaemic infiltrates came from the malignant mastocytosis group; eosinophilia, plasmacytosis and fibrosis were seen significantly more often in malignant than in systemic mastocytosis, but blood vessel hyperplasia and germinal centre hyperplasia were encountered with the same high frequency in both groups; and mast cell atypia tended to be more pronounced in malignant mastocytosis; this diagnosis could therefore easily be missed without naphthol AS-D chloroacetate esterase staining.(ABSTRACT TRUNCATED AT 250 WORDS)

Humans↗
PubMed1992

Clonal analysis of agnogenic myeloid metaplasia.

Agnogenic myeloid metaplasia (AMM) is a chronic myeloproliferative disorder that leads to a sustained proliferation of megakaryocytes and an increase of reticulin fibers within the bone marrow. Blood and bone marrow samples from patients with advanced AMM with fully developed myelofibrosis as well as cases in the cellular phase of the disease were investigated for clonality. Clonality was studied by X-linked restriction length polymorphism in conjunction with DNA methylation patterns. Granulocytes and total bone marrow cells proved to be monoclonal in origin whereas at least a minor portion of the peripheral lymphocytes were not clonally derived. Our findings indicate that the cellular phase of AMM as well as the fully developed disease progressed to myelofibrosis represent a monoclonal proliferation of pluripotent hematopoietic stem cells.

Bone Marrow↗
PubMed1992

[Heterogeneous Epstein-Barr virus infection patterns in peripheral T cell lymphoma of the angioimmunoblastic lymphadenopathy type].

32 cases of T cell lymphoma of angioimmunoblastic lymphadenopathy type (AILD-TCL) were investigated for their association with Epstein-Barr virus (EBV). Polymerase chain reaction (PCR) for detection of EBV-DNA and in situ hybridization for EBV-encoded small nuclear RNAs (EBER) produced almost identical results, showing that all but one of AILD-TCL cases contained EBV genomes. Three distinctive patterns of EBV infection were observed after immunophenotypical characterization of EBER positive cells: 1. predominant infection of B-immunoblasts (26% of the cases), 2. predominant infection of neoplastic T cells (42% of the cases) and 3. infection of few small lymphocytes (32% of the cases). EBV-encoded latent membrane protein was frequently detectable in cases exhibiting patterns 1 and 2. These findings suggest that, in AILD-TCL patients B cells and especially T cells are highly susceptible to a persistent EBV infection which may lead to a growth advantage of infected cells.

DNA, Viral↗
PubMed1992

[EBV-lymphadenitis: diagnostic possibilities using immunohistochemistry and in situ hybridization].

EBV infections were studied in paraffin embedded lymph node specimens (n = 20) on DNA, protein, and histological level. The lymph nodes were obtained from 20 patients all testing positive for EBV serologically. The EBV DNA was detected by non radioactive in-situ-hybridisation using the BamHI W fragment of the virus. The EBV latent membrane protein was detected immunohistochemically using the LMP antibody (DAKO). Infected cells were characterized by monoclonal B cell antibodies. By in-situ-hybridization we found positive signals for EBV in all specimens. In contrast, no LMP was detectable immunohistochemically in 2/20 lymph nodes.

Antibodies, Monoclonal↗
PubMed1992

[Sinus lining cells:morphology, function and neoplasia].

Lymph node sinuses consist mainly of sinus lining cells with clear dendritic morphology. Enzyme cytochemical and immune phenotypical analysis classify sinus lining cells as an intermediate cell type linking monocyte/macrophage to follicular dendritic cells, which are accepted immune accessory cells to humoral immune response. Labeling studies indicate sinus lining cells to hematogenous and possible monocytogenous in origin. In functional term sinus lining cells bind and present soluble antigen as the first cell type following antigen pulse. In addition sinus lining cells bind carcinoma cells and may play a role in metastasis. Sinus lining cells give rise to a well defined entity of neoplasia which is proposed to be termed sinus lining cell reticulosarcoma. In this presentation a case report exemplifies such a new entity.

Acid Phosphatase↗
PubMed1992

Lineage-specific methylation of the c-fms gene in blood cells and macrophages.

DNA methylation belongs to the multilevel genetic control system regulating differentiation processes and gene expression. The extent to which DNA methylation contributes to the differentiation of hematopoietic cells is elusive. In the present study we investigated the methylation state of the c-fms/M-CSF receptor gene in normal human blood cells and tissue macrophages. The methylation pattern of the c-fms gene as detected by isoschizomeric restriction analysis with MspI/HpaII showed only slight interindividual variations in normal donors, whereas constant differences were found between granulocytes and monocytes from the same donor. The second intron of the c-fms gene contains several CpG loci which were found to be hypomethylated on both alleles in monocytes and tissue macrophages. By contrast, these positions were methylated in granulocytes and lymphocytes that did not express the c-fms gene. In comparison to monocytes alveolar and peritoneal macrophages revealed an enhanced demethylation. There were constant differences in c-fms gene methylation between alveolar and peritoneal macrophages with a higher degree of demethylation in alveolar macrophages. We conclude that c-fms gene demethylation is involved in the differentiation of monocytes and macrophages from immature precursors and that the demethylation of lineage-specific growth factor receptor genes might provide an important step in lineage commitment of hematopoietic cells.

Alleles↗
PubMed1991

Clonal granulocytes and bone marrow cells in the cellular phase of agnogenic myeloid metaplasia.

Myelofibrosis with myeloid metaplasia (MMM) belongs to the group of myeloproliferative syndromes. It is characterized by a sustained proliferation of megakaryocytes and increased medullary reticulin fibers. Until now the cellular phase at onset of the disease has not been analyzed for clonality of the hematopoietic cells. In this study we used X-linked restriction length polymorphism (RFLP) analysis to investigate the clonality of granulocytes and bone marrow cells from the cellular phase and advanced stages of the disease. In each of 12 heterozygous females, monoclonality of granulocytes or total bone marrow cells could be demonstrated. These results show that the cellular phase represents a monoclonal, and hence a probably neoplastic, proliferation of a pluripotent stem cell. The monoclonality of granulocytes present at the onset of disease should allow analysis of DNA of these easily accessible peripheral cells for the detection of specific clonal aberrations.

Adult↗
PubMed1991

cDNA cloning and characterization of human monocyte/macrophage serine esterase-1.

Human monocyte/macrophage serine esterase (HMSE), commonly known as acid esterase or alpha-naphthylacetate esterase, comprises a group of five enzyme variants that can be distinguished by their isoelectric points from esterase variants of the other normal human blood cell populations. A cDNA for one of the monocytic enzyme variants (HMSE1) was cloned from a U-937 lambda gt11 cDNA library by screening with an oligonucleotide mixture designed according to amino acid sequence data of the purified enzyme. The cDNA contains 1,727 bp with an open reading frame of 1,512 bp coding for a protein of 503 amino acid residues. HMSE1 cDNA represents the first cloned monocyte/macrophage-specific serine esterase and its sequence shows up to 77% homology to other known serine esterases of different species. The amino acid composition of the putative active site of HMSE1 as deduced from the nucleotide sequence corresponds with the active sites of other serine esterases but not with the active sites of serine proteases. Hybridization of the cDNA with RNA of separated normal blood cell populations and hematopoietic cell lines shows restricted expression within the monocyte/macrophage lineage.

Amino Acid Sequence↗
PubMed1991

Ki-B5: a monoclonal antibody unrelated to CD45 recognizes normal and neoplastic human B cells in routine paraffin sections.

In the search for immunoreagents appropriate for the histopathologic diagnosis of malignant B-cell lymphomas in routinely processed paraffin sections, a new monoclonal antibody, Ki-B5, was generated using a high-grade B-cell lymphoma as the immunogene. Ki-B5 is a mouse IgG1/kappa that recognizes five protein fractions of about 84, 82, 55, 48, and 27 Kd after biosynthetic radiolabeling and immunoprecipitation. Protein fractions with the molecular weights of approximately 84 and 82 Kd were expressed on the cell surface and show that Ki-B5 is probably unrelated to CD45. It was possible through electron microscopy to visualize the membrane-bound portion of Ki-B5. Extensive immunohistologic studies on normal human tissue and various neoplasias demonstrated the high specificity of Ki-B5 to normal human B cells and a minor subgroup of plasma cells. Except for ML-2, which is a myelomonocytic human cell line, Ki-B5 exclusively recognized the B-cell lineage, including EB-3, BALL-1, and NALM-1. All carcinomas, sarcomas, and malignant melanomas tested with Ki-B5 were negative. Although normal granulocytes and monocytes were constantly negative, three of eight myelomonocytic leukemias coreacted with this antibody. Eight of the 57 T-cell lymphomas studied were positive to Ki-B5. Five were classified as lymphoblastic, two represented T8-CLL, and one was classified as immunoblastic T-cell lymphoma. Only 3 of 126 cases of B-cell lymphoma, including rare types not considered in the current classifications, were negative to Ki-B5. Plasmacytomas were also negative, except for one case. Irrespective of the cases of lymphoblastic lymphoma and plasmacytoma, Ki-B5 represents a new monoclonal antibody appropriate for the diagnosis and immunophenotyping of malignant lymphomas in routinely processed paraffin sections.

Animals↗
PubMed1991

Follicular dendritic cells in Hodgkin's disease.

The distribution of follicular dendritic cells (FDCs) was studied in 66 lymph nodes affected by Hodgkin's disease (HD) from as many patients with the use of the monoclonal antibody Ki-FDC1P, which stains FDCs in paraffin sections. Two distinct FDC patterns were distinguishable in the neoplastic areas: pattern A, showing FDC networks occupied by nongerminal center cells, often expanded and disrupted; and pattern B, with FDCs rare or lacking. Pattern A, with follicle-occupying cells represented by epithelioid and lymphocytic and histiocytic (L and H) cells, was found in about 90% of the cases of nodular lymphocyte predominance type and in about half of the cases of nodular sclerosis type, with the follicle-occupying cells being lacunar cells. In the group of mixed cellularity type, approximately one-fifth of the cases exhibited pattern A and in these cases the follicle-occupying cells were Sternberg-Reed, Hodgkin's, and epithelioid cells. The presence of follicular structures, although abnormal, is a more common occurrence in HD than is appreciable with the use of conventional histologic methods.

Antibodies, Monoclonal↗
PubMed1991

Increased expression of growth factor genes for macrophages and fibroblasts in bronchoalveolar lavage cells of a patient with pulmonary histiocytosis X.

Pulmonary histiocytosis X is the local manifestation of a systemic disorder of unknown cause characterised by infiltration of Langerhans cell like histiocytes and parenchymal fibrosis. In a male smoker with histologically proved histiocytosis X and functional impairment bronchoalveolar lavage showed an increase in CD-1/OKT-6 antigen positive histiocytes to 8%. Northern blot analysis of RNA from bronchoalveolar lavage cells showed an exaggerated expression of the M-CSF gene and of the c-fms gene encoding for the corresponding receptor. An increased level of c-sis RNA, which encodes the B chain of platelet derived growth factor, was also found. Diffuse reticulonodular infiltrates on the chest radiograph resolved with glucocorticoid treatment and CD-1/OKT-6 antigen positive histiocytes fell to 3%. Macrophage colony stimulating factor, c-fms and c-sis gene expression were reduced almost to normal after treatment. The results suggest that macrophage colony stimulating factor and platelet derived growth factor may have a role in the initiation or maintenance of pathological reactions in pulmonary histiocytosis X.

Adult↗
PubMed1991

Increased methylation of the c-fms protooncogene in acute myelomonocytic leukemias.

DNA methylation provides an epigenetic information possibly involved in differentiation processes and gene regulation. In this study we investigated the methylation state of the c-fms/M-CSF receptor gene in normal human blood cells and leukemias. The methylation pattern of the c-fms gene as detected by isoschizomeric restriction analysis with MspI/HpaII showed only slight interindividual variations in normal donors, but there were constant differences between granulocytes and monocytes from the same donor. Of 21 acute myelomonocytic leukemias investigated, 85% revealed a methylation pattern different from that of normal monocytes. One or more restriction sites which were at least partly unmethylated in normal monocytes proved to be methylated in leukemic cells. In contrast, leukemias of lymphocytic origin showed hypomethylation of the c-fms gene. There was no correlation between the methylation state of the c-fms gene and its expression at the RNA level, but an increase in monocyte/macrophage-specific differentiation markers could be observed in those samples which exhibited a methylation pattern similar to that of normal monocytes. The increased DNA methylation within the c-fms gene might reflect the inactivation of differentiation genes in leukemic cell clones, contributing to their maturation arrest. Furthermore, neoplastic hematopoietic cells seem to exhibit lineage-specific differences in c-fms gene methylation.

Adolescent↗
PubMed1991

Alveolar macrophages in idiopathic pulmonary fibrosis display a more monocyte-like immunophenotype and an increased release of free oxygen radicals.

Bronchoalveolar lavage (BAL) was performed in 13 patients with idiopathic pulmonary fibrosis (IPF) and in 10 control subjects. Free oxygen radical (FOR) production of alveolar macrophages (AM) and of blood monocytes was measured by luminol-dependent chemiluminescence (LDCL) without and after stimulation with zymosan A. We confirmed earlier studies that alveolar macrophages of IPF patients display a significantly elevated release of FOR under basic and under stimulated conditions. In contrast to alveolar macrophages, blood monocytes did not reveal altered LDCL in IPF. This indicates that the functional properties for augmented FOR release by IPF alveolar macrophages are acquired in the lungs and not in the peripheral circulation. To elucidate the possible mechanisms leading to the augmented LDCL response, immunophenotyping of alveolar macrophages was carried out. A panel of new monoclonal antibodies of the Ki-M-series, discriminating differentiation stages of monocyte/macrophage subpopulations, served for immunocytochemical staining. In IPF patients distribution of Ki-M2, Ki-M3, Ki-M6 and Ki-M8 positive AM demonstrated an increased proportion of alveolar macrophages expressing a more monocyte-like immunophenotype. Normally, monocytes as precursors of AM reveal a markedly stronger LDCL than alveolar macrophages themselves. Therefore, it seems likely that the increased LDCL of alveolar macrophages in IPF is due to the higher proportion of more immature monocyte-like cells in the alveoli of these patients.

Antibodies, Monoclonal↗
PubMed1991

Detection of a monocyte/macrophage differentiation antigen in routinely processed paraffin-embedded tissues by monoclonal antibody Ki-M1P.

A new monoclonal antibody Ki-M1P that is raised against supernatants of detergent solubilized human lymph node tissue is described. Ki-M1P recognizes in particular monocytes and their macrophage derivatives as tested by light- and electron-microscopic immunohistochemistry. Granulocytes, dendritic cells as the accessory cells of humoral and cellular immune response, and epithelial, endothelial, neural, and mesenchymal cells do not react with Ki-M1P. In extensive application Ki-M1P has proven to be a useful marker for distinguishing monocytic leukemias within FAB groups M4 and M5. The recognized antigen is composed of five proteins with molecular masses of about 60, 92, 98, 124, and 150 kDa in blood monocytes, whereas tissue macrophages tested so far expressed only the 60-kDa protein. Because the Ki-M1P antigen is not destroyed or masked during routine fixation and paraffin embedding of biopsy tissue samples, Ki-M1P represents a useful diagnostic reagent for the identification of physiological functional and pathologic reaction forms as well as neoplastic variants of the human monocyte/macrophage system even in retrospective studies.

Animals↗
PubMed1990

Six new monoclonal antibodies to serous, mucinous, and poorly differentiated ovarian adenocarcinomas.

Six monoclonal antibodies directed against ovarian adenocarcinoma were generated by use of 100,000 x g supernatants of Triton-X-100 solubilized extracts of ovarian serous adenocarcinoma as the antigen source. Immunoperoxidase preparation of frozen-sections and routinely processed paraffin section specimens revealed a highly restricted reactivity of these antibodies when tested with adult (n = 2) and fetal (n = 3) tissue types. Coreactivities were occasionally observed with epithelia of the kidney, mammary gland, and pancreas. One monoclonal antibody, Ki-OC I-6-2, cross-reacted only with epididymal epithelia. No coreaction occurred with normal tissue of the ovary, Fallopian tube, or uterus. All antibodies were additionally tested on 74 cases of nonovarian malignancies, 15 cases of ovarian metastases of nonovarian carcinomas, and 114 specimens of ovarian neoplasms other than carcinomas. Ki-OC I-6-2 had no cross-reactivity with these tumors except for one case of renal cell carcinoma. This monoclonal antibody recognized serous, mucinous, and poorly differentiated adenocarcinoma cell types. None of the six antibodies reacted with clear cell or endometrioid carcinoma. All were found to be of the IgG-1 subclass. The tumor antigen to which Ki-OC I-6-2 immunoreacted was estimated to have a molecular weight of 80 kilodaltons (KD).

Adult↗