muramidase and Lymphoma--Large-B-Cell--Diffuse

The primo vascular system (PVS), which is composed of very small primo-vessels (PV) and primo-nodes (PN), has recently emerged as a third component of circulatory system. Here, we report the presence of a tumor derived PVS in murine xenografts of human histiocytic lymphoma (U937) in close proximity to the tumor. Within this system, PNs are small (~500-600 μM diameter) membranous sac-like structures which contain numerous small cells which can be demonstrated by DAPI staining. Hematoxylin and Eosin (H&E) staining of the peri-tumoral PVS shows the presence of loose structures lined by fibroblasts but filled with dense fibers, cells, lacunae and nerve-like structures. The origin and type of cells within the PVS was characterized by immunostaining with antibodies for CD68, CD45 and lysozyme. The results of these studies reveal that the PVS of the xenograft originates from the human U937 tumor cells. qRT-PCR analysis of mRNA isolated from PVS cells reveals a striking predominance of human, rather than mouse, sequences. Of particular interest, human stem cell specific transcription factors were overexpressed, most notably KLF4, an upstream regulator of NANOG which maintains the pluripotent and undifferentiated state of stem cells. These results suggest that the cells present within the PVS are derived from the human xenograft and suggests that the primo-vessels associated with the xenografted tumor may provide a safe haven for a select population of cancer stem cells. Further understanding of the biological properties of these cells may allow the development of new anti-cancer interventions.

Topics: Animals; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Cell Line, Tumor; Humans; Kruppel-Like Factor 4; Kruppel-Like Transcription Factors; Leukocyte Common Antigens; Lymphoma, Large B-Cell, Diffuse; Meridians; Mice; Mice, Inbred BALB C; Mice, Nude; Muramidase; Neoplasm Transplantation; Neoplastic Stem Cells; RNA, Messenger; Stem Cell Niche; Transplantation, Heterologous; U937 Cells

To study the morphologic features, immunophenotypes, differential diagnoses and prognosis of histiocytic sarcoma (HS).. The clinical and pathologic findings of 6 cases of HS were reviewed. Immunohistochemical assay (Elivision staining) was also performed. Follow-up information was available in 4 patients.. There were altogether 3 males and 3 females. The age of patients ranged from 12 to 81 years old (median = 54.6 years). The sites of involvement included lymph node (number = 2 cases) and skin or soft tissue (number = 4 cases). The tumor was composed of sheets of large epithelioid cells with abundant eosinophilic cytoplasm, oval to irregular nuclei, vesicular chromatin and large nucleoli. Binucleated form was not uncommon. Two of the cases showed increased pleomorphism with multinucleated tumor giant cell formation. Focal cytoplasmic with foamy appearance was identified in 3 cases. One case demonstrated foci of spindly sarcomatoid appearance. Hemophagocytosis was identified in 2 cases. Mitotic figures were readily identified. The tumor cells were often accompanied by various numbers of inflammatory cells. Immunohistochemical study showed that all cases were diffusely positive for leukocyte common antigen, CD4, CD68 and CD163. Four of the 5 cases studied also expressed lysozyme. Amongst the 4 patients with follow-up information available, 3 died of the disease at 6 to 11 months interval after diagnosis. One patient, whose lesion was localized at the skin and soft tissue, survived for 3 years, with no evidence of tumor recurrence.. Accurate diagnosis of the HS is based on the combination of morphologic examination and immunohistochemical assay. HS often presents with clinically advanced disease and pursues an aggressive clinical course, with a poor response to therapy. However, a subset of cases presenting with clinically localized lesion may carry a relatively favorable long-term outcome.

Topics: Adult; Aged; Aged, 80 and over; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Carcinoma, Renal Cell; Child; Diagnosis, Differential; Female; Follow-Up Studies; Histiocytic Sarcoma; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Large-Cell, Anaplastic; Male; Melanoma; Muramidase; Prognosis; Receptors, Cell Surface; Skin Neoplasms; Soft Tissue Neoplasms; Young Adult

Twenty cases of histiocytic sarcoma in 15 female and five male (384 to 722 days of age) hybrid F1 (C57BL/6 x BALB/c) or F2 (F1 x F1) mice were studied for expression of mononuclear phagocyte and other antigens. Histiocytic sarcomas were found most often in liver, uterus, spleen, and lung. Tissues fixed in Bouin's fluid provided preservation of antigen immunoreactivity, using avidin biotin peroxidase complex immunohistochemistry, with monoclonal and polyclonal antibodies. The mononuclear phagocyte antigens, lysozyme and Mac-2 (a galactose-specific lectin that binds IgE), were found in 60-70% of the cases. The receptor for the macrophage colony-stimulating factor (CSF-1), c-fms, was expressed in 2/20 (10%) of the cases. Mouse immunoglobulins were not found in histiocytic sarcoma cells. In uterine histiocytic sarcomas, previously reported as Schwannomas because of their histologic appearance, S-100 protein was not expressed by tumor cells, although they usually expressed Mac-2 and lysozyme. Hyaline droplets were found in the renal tubules of only 2/19 cases. Our studies provide evidence that murine histiocytic sarcoma expresses antigens (Mac-2, lysozyme, c-fms) found in cells of the mononuclear phagocyte series, in contrast to the B-cell origin of many human histiocytic tumors.

Topics: Animals; Antigens, Differentiation; Female; Galectin 3; Lymphoma, Large B-Cell, Diffuse; Male; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Muramidase; Retrospective Studies

The extracellular matrix influences the growth and differentiation of a variety of cell types. In this study, the effects of bone marrow extracellular matrix on U-937 cells, a human histiocytic lymphoma cell line, were assessed. Sixty percent of U-937 cells adhered to extracellular matrix, whereas only 1% adhered to uncoated plastic. U-937 cells grown on extracellular matrix released significantly more lysozyme into the medium (8.3 +/- 0.3 micrograms/10(6) cells) compared to those grown on plastic (4.2 +/- 0.5 micrograms/10(6) cells). FMLP (f-met-leu-phe) receptor expression was also enhanced suggesting a more mature phenotype in cells grown on matrix (2980 cpm/10(6) cells vs 230 cpm/10(6) cells on plastic). Furthermore, bone marrow extracellular matrix inhibited proliferation of U-937 cells. After four days in culture, there was a 65% inhibition of cell growth in matrix-coated flasks compared to uncoated flasks. Since an arrest in G0/G1 usually precedes mammalian cell differentiation, DNA histograms were performed on U-937 cells grown on matrix to detect such an arrest. However, the cell cycle distribution of U-937 cells grown on extracellular matrix or uncoated plastic for various time periods was similar. In contrast, bromodeoxyuridine pulse labeling revealed approximately a 5 hr prolongation in cycle length in cells grown on extracellular matrix. We conclude that bone marrow extracellular matrix induced macrophage-like differentiation and inhibited proliferation of U-937 cells with a prolongation of the cell cycle that was not G0/G1 phase specific.

Topics: Bone Marrow; Cell Adhesion; Cell Communication; Cell Cycle; Cell Differentiation; Cell Line; Extracellular Matrix; Humans; Lymphoma, Large B-Cell, Diffuse; Muramidase; N-Formylmethionine Leucyl-Phenylalanine; Receptors, Formyl Peptide; Receptors, Immunologic

Immunologic studies have demonstrated that the vast majority of hematolymphoid neoplasms previously designated as "histiocytic" are lymphoid in origin. Consequently, malignancies of macrophage lineage are considered rare by most authors; indeed, their existence is doubted by some. Herein we report two cases of malignant histiocytic neoplasms (malignancies of macrophage lineage) of the small intestine. Both patients presented in the 7th decade with symptoms related to an abdominal mass. The polypoid tumors protruded into the intestinal lumen, extended through the entire thickness of the bowel wall, and involved regional lymph nodes. Microscopically, sheets of large pleomorphic histiocytic cells infiltrated around crypts and were associated with an admixture of bizarre giant cells and inflammatory cells. Mitotic figures were easily found. Ultrastructurally, the cells lacked desmosomes and had indented or kidney-shaped nuclei and cytoplasm containing mostly lysosomes and dense lipid droplets. In both cases, paraffin section immunohistochemistry revealed reactivity of tumor cells for CD45RB (LCA), CD45RO (A6), CD68 (KP1), CD15 (LeuM1), and lysozyme. Frozen section immunohistochemistry performed in one case further supported the macrophage phenotype. Southern blot studies of this case did not reveal immunoglobulin or T-cell receptor beta chain gene rearrangements. One patient initially treated by surgery only died of disease 3 years after diagnosis. The second patient is alive and disease-free 2 years following postoperative combination chemotherapy. The diagnosis of malignant histiocytic neoplasms requires the use of a panel of immunohistochemical markers and may be supported by electron-microscopic studies.

Topics: Antigens, CD; Biomarkers, Tumor; Blotting, Southern; Cell Transformation, Neoplastic; DNA, Neoplasm; Gene Rearrangement; Humans; Immunohistochemistry; Intestinal Neoplasms; Intestine, Small; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Macrophages; Male; Microscopy, Electron; Middle Aged; Muramidase

Topics: Adult; Aged; alpha 1-Antitrypsin; Biomarkers, Tumor; Diagnosis, Differential; Female; Humans; Immunohistochemistry; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Muramidase

Differentiation-inducing agents have recently been applied clinically in various myeloproliferative diseases, based on their in vitro ability to induce differentiation in myeloid and monocytic cell lines. In this study we compared the abilities of two agents, dibutyryl cyclic AMP (DBcAMP) and retinoic acid (RA) to induce monocytic functions in the human histiocytic lymphoma cell line U937. Both agents produced similar induction of phagocytosis and reduction of nitroblue tetrazolium (NBT). Other monocytic functions, including accumulation of lysozyme, spontaneous and directed migration toward zymosan-activated serum (ZAS), the chemotactic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and leukotriene B4 (LTB4) were induced by DBcAMP, while RA induced migration toward LTB4 only. Simultaneous treatment with both inducers proved synergistic only with respect to phagocytosis. NBT reduction and migration toward FMLP and LTB4 were unchanged, while migration toward ZAS and lysozyme accumulation were suppressed by the addition of RA. The results suggest that the inducer affects the expression of cellular functions and characteristics specific to a particular lineage. In addition, the data presented indicate that the U937 cell line may serve as an excellent model system for the study of the regulation and mechanisms of chemotactic receptor expression in monocytes.

Topics: Bucladesine; Cell Differentiation; Cell Line; Cell Movement; Chemotaxis, Leukocyte; Humans; L-Lactate Dehydrogenase; Lymphoma, Large B-Cell, Diffuse; Monocytes; Muramidase; Phagocytosis; Tretinoin

1. The activities of nine glycosidases, lysozyme and acid and alkaline phosphatases were compared in the histiocytic lymphoma cell line U-937 and a set of clones and sublines derived from this line. 2. The patterns of the different enzyme activities and selected enzyme ratios have been used as a method to distinguish between different clones and sublines. 3. Sublines with high lysozyme levels were rich in most cell-bound glycosidases. 4. During long-term growth distinct enzyme patterns of individual lines were preserved. 5. The enzyme pattern during a cell culture growth cycle was basically stable.

Topics: Acid Phosphatase; Alkaline Phosphatase; Cell Division; Clone Cells; Glycoside Hydrolases; Humans; Lymphoma, Large B-Cell, Diffuse; Muramidase; Time Factors; Tumor Cells, Cultured

A comparative study of large cell lymphoma (LCL) (ten B and ten T), Hodgkin's disease (15 cases), and true histiocytic lymphoma (two cases) was undertaken, using formalin-fixed paraffin-embedded tissue sections, a panel of eight antibodies, and one lectin to determine if any particular antibody or immunologic profile could reliably distinguish between these entities. The antibodies used were against Leu-M1, alpha-1-anti-chymotrypsin (alpha-ACT), alpha-anti-trypsin (alpha-AT), lysozyme, kappa, lambda, leukocyte common antigen (LCA), and S-100 protein. The lectin used was peanut agglutinin (PNA). Although Leu-M1 staining was positive in 11 of 15 cases (73%) of Hodgkin's disease, it was also positive in 4 of 10 cases (40%) of T-cell lymphoma, 2 of 10 cases (20%) of B-cell lymphoma, and 1 of 2 cases (50%) of true histiocytic lymphoma. Peanut-agglutinin staining results were similar to Leu-M1. The only staining profile that emerged was the presence of Leu-M1, PNA-, alpha-ACT, and alpha-AT staining in Reed-Sternberg (RS) cells in 11 of 15 cases of Hodgkin's disease. Leu-M1 and its staining pattern is characteristic, but not entirely specific for RS cells, and it was not positive in at least 25% of the cases of Hodgkin's disease in formalin-fixed, paraffin-embedded tissues. The limitations of this antibody and others should be recognized.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Antigens, Neoplasm; Histocompatibility Antigens; Hodgkin Disease; Humans; Immunoenzyme Techniques; Lectins; Leukemia, Lymphocytic, Chronic, B-Cell; Leukocyte Common Antigens; Lymphoma, Large B-Cell, Diffuse; Muramidase; Peanut Agglutinin; S100 Proteins

Immunoreactive lysozyme was readily detectable in canine histiocytic disorders including systemic histiocytosis, malignant histiocytosis and granulomatous panniculitis. Lysozyme was less reliable as a histiocytic marker in cutaneous histiocytoma; forty percent of these tumors were negative for lysozyme expression. The marked heterogeneity in lysozyme expression in cutaneous histiocytoma may indicate that a proportion of these tumors show relatively primitive histiocytic differentiation and do not express lysozyme. Alternatively, this same proportion may exhibit a phenotype akin to cutaneous Langerhans cells which do not contain lysozyme. Lysozyme was not detectable in the tumor cells in lymphomatoid granulomatosis, atypical cutaneous histiocytoma, and histiocytic lymphosarcoma. Other evidence that these three disorders do not represent true histiocytic proliferative disorders is discussed.

Topics: Animals; Cytoplasm; Dog Diseases; Dogs; Histiocytes; Histiocytic Sarcoma; Histiocytoma, Benign Fibrous; Lymphoma, Large B-Cell, Diffuse; Lymphomatoid Granulomatosis; Lymphoproliferative Disorders; Muramidase

A retrospective study of 76 primary gastrointestinal lymphomas utilizing an avidin: biotinylated horseradish peroxidase complex (ABC) technique demonstrated 22 B-cell lymphomas, including two associated with alpha-heavy chain disease. Seven cases were classified as true histiocytic lymphomas based on a positive reaction for one or more of three histiocytic enzyme markers utilized, predominantly alpha-1-antitrypsin and alpha-1-antichymotrypsin. However, in 20 cases, an intense admixture of reactive histiocytes was noted and these cells stained preferentially for the enzyme, lysozyme. Twenty cases, which stained for both kappa and lambda light chains and positively or negatively for albumin, could not be classified and 27 cases failed to stain with any of the antisera utilized.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Antibodies; B-Lymphocytes; Chymotrypsin; Gastrointestinal Neoplasms; Heavy Chain Disease; Histocytochemistry; Humans; Immunoenzyme Techniques; Immunoglobulin alpha-Chains; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Muramidase

Topics: alpha 1-Antitrypsin; Histiocytes; Humans; Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Muramidase; Phenotype; S100 Proteins; T-Lymphocytes; Terminology as Topic

Large-cell non-Hodgkin's lymphomas (T- and B-immunoblastic, centroblastic and true histiocytic lymphomas) have a heterogeneous clinical course. In the present study the clinical and morphological data of 20 cases of histiocytic sarcoma (true histiocytic lymphoma) are presented. Diagnosis was supported by immunohistochemistry, cytochemistry, rosette assays and/or electron microscopy. Although the follow-up was relatively short (up to 144 months, mean 26 months), the clinical data differed clearly from the series of large-cell non-Hodgkin lymphomas, recorded in the literature. Differences were found in age distribution with a peak in the third decade, in organ involvement showing a preference for skin, gastrointestinal tract and bone, and in response to therapy. In general, histiocytic sarcoma appears to have a more favourable response to therapy and clinical course than the other large-cell lymphomas (T- and B-immunoblastic and centroblastic lymphomas). Moreover, preliminary observations in the group of histiocytic sarcomas suggested that the presence of lysozyme and/or 5-nucleotidase and the absence of alpha 1-antitrypsin in the cytoplasm is associated with a better response to therapy and favourable clinical course.

Topics: 5'-Nucleotidase; Adult; Aged; alpha 1-Antitrypsin; Female; Histocytochemistry; Humans; Immunologic Techniques; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Muramidase; Nucleotidases; Prognosis

Using the peroxidase antiperoxidase (PAP) method, lysozyme (LZM) was shown to exist in normal, reactive and neoplastic cells belonging to the mononuclear phagocyte system (MPS), but was not detected in histiocytosis X cells. Immunostaining for cytoplasmic LZM by the PAP method is useful for identification of mononuclear phagocytes and for diagnosis of the diseases in which these cells participate.

Topics: Granulomatosis with Polyangiitis; Histiocytes; Hodgkin Disease; Humans; Immunoenzyme Techniques; Inflammation; Leukemia, Myeloid; Lymphadenitis; Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Mononuclear Phagocyte System; Muramidase; Neoplasms

Human blood-borne monocytes were cultured for up to 22 days on disposable Teflon foils. Within 8 days, these monocytes developed into mature macrophages. At various stages of differentiation, the cells were recovered from the hydrophobic membrane and were assayed for typical monocyte-macrophage enzymes and morphology, binding of monoclonal antibodies (OKM1, OKla1), Fc and transferrin receptors, phagocytic activity, lysozyme production, and ability to inhibit the growth of an allogeneic tumor target cell line (U937). A significant antitumor activity of mature macrophages was found, which developed along with the differentiation of the monocyte precursor cells. In addition, cytotoxic effector macrophages could be activated by lymphokine-rich medium and synthetic alkyl-lysophospholipids. After density gradient separation, light cells (less than 1.05 and less than 1.06 g/ml) showed enhanced cytotoxicity, whereas cells from the dense fraction (greater than 1.06 g/ml) with low base-line activity could be best activated for cytotoxicity by lymphokines. If monocyte-macrophages are involved in a natural surveillance mechanism, our results may indicate the importance of unimpaired macrophage maturation to generate effective host defense against tumor development.

Topics: Cell Adhesion; Cell Differentiation; Cell Line; Cell Separation; Cells, Cultured; Cytotoxicity, Immunologic; Humans; Lymphokines; Lymphoma, Large B-Cell, Diffuse; Macrophages; Monocytes; Muramidase

The clinical and histologic data from 12 patients with "reticulum cell sarcoma" (large cell lymphoma) presenting in the skin were reviewed. Moreover, when appropriate material was available additional immunological, cytochemical and ultrastructural techniques were used to define the nature of the neoplastic cells. Eight tumors were found to be of true histiocytic origin (histiocytic sarcoma), three of B-cell origin (two B-immunoblastic lymphomas and one centroblastic or large noncleaved follicle center cell lymphoma) and one case could not be classified. Possible explanations for the discrepancy between the current report and other studies as to the frequency of true histiocytic tumors will be discussed. The differentiation into T-cell, B-cell and true histiocytic lymphomas appears to be important, not only because of different clinical behaviour, but possibly also from a therapeutical point of view.

Topics: Adult; Aged; alpha 1-Antitrypsin; Enzymes; Female; Follow-Up Studies; Histocytochemistry; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Microscopy, Electron; Middle Aged; Muramidase; Skin Neoplasms

Lymph node specimens obtained intraoperatively and/or at autopsy from 89 patients with non-Hodgkin's lymphoma were studied immunohistochemically. The peroxidase anti-peroxidase (PAP) technique was used for detecting monoclonal cytoplasmic immunoglobulin (CIg) and for determining the classes and types of immunoglobulins in the tumors. Following rigid criteria, monoclonal CIg was demonstrated in four (16%) of 25 cases of nodular, poorly differentiated lymphocytic lymphoma (NPDL); in three (14%) of 21 cases of diffuse, poorly differentiated lymphocytic lymphoma (DPDL); and in 13 (30%) of 43 cases of diffuse histiocytic lymphoma (DH). Of the four NPDL patients, two had the M kappa, one the A kappa, and one the lambda chain type. Of the three DPDL patients, one had the M kappa, one the G kappa, and one the lambda chain type. Of the 13 DH patients, five had the M kappa, four the A kappa, one the GM kappa, one the A kappa, one the G kappa, and one the kappa chain type. In two DH patients negative for cytoplasmic immunoglobulins, cytoplasmic lysozyme was present, indicating the histiomonocytic nature of the tumor cells. There was no significant difference between the overall survival rates for the DH patients with or without monoclonal CIg. In all three types of lymphoma studied, we encountered many patients (67%) who had tumor cell populations without demonstrable CIg and few patients (11%) with polyclonal CIg. There are several possible reasons why many of the patients were PAP-negative and why some had polyclonal cell populations. The PAP method may be useful in establishing the monoclonal nature of neoplastic lymphoid cell populations.

Topics: Antibodies, Monoclonal; B-Lymphocytes; Cytoplasm; Humans; Immunoenzyme Techniques; Immunoglobulin Light Chains; Lymph Nodes; Lymphoma, Large B-Cell, Diffuse; Muramidase; Prognosis

Topics: Adolescent; Adult; Age Factors; B-Lymphocytes; Child; Child, Preschool; Female; Histiocytes; Humans; Immunoglobulins; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Muramidase; Phenotype; T-Lymphocytes

Malignant histiocytosis (MH) is a rare, usually fatal systemic disease considered to be a neoplasm of true histiocytes. Because MH may be difficult to differentiate from non-Hodgkin's lymphomas or carcinoma, we examined surgical and autopsy material from 10 patients with MH using the immunoperoxidase technique to determine if the presence of intracellular lysozyme is helpful in making this distinction. The cases of MH were divided into three groups based on the degree of cytologic atypia and the amount of phagocytic activity of the neoplastic cells: group I--minimal cytologic atypia and rare erythrophagocytosis; group II--minimal cytologic atypia with extensive erythrophagocytosis: group III--moderate to marked cytologic atypia and rare phagocytosis. Moderate to strong staining for lysozyme was observed in the neoplastic cells of group I, weak or absent staining in group II cells, and no staining in group III cells. These findings suggest the loss of detectable enzyme in poorly differentiated or dedifferentiated neoplastic histiocytes. Consideration must be given to these observations in evaluating the use of lysozyme as a possible serum or tissue aid to the diagnosis of MH.

Topics: Adolescent; Adult; Aged; Cell Differentiation; Diagnosis, Differential; Female; Histiocytes; Histocytochemistry; Humans; Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Muramidase; Phagocytosis

The clinical and laboratory features of 37 patients with variants of acute monocytic leukemia are described. Three of these 37 patients who had extensive extramedullary leukemic tissue infiltration are examples of true histiocytic "lymphomas." Three additional patients with undifferentiated leukemias, one patient with refractory anemia with excess of blasts, one patient with chronic myelomonocytic leukemia, one patient with B-lymphocyte diffuse "histiocytic" lymphoma and one patient with "null" cell, terminal deoxynucleotidyl transferase-positive lymphoblastic lymphoma had bone marrow cells with monocytic features. Another patient had dual populations of lymphoid and monocytoid leukemic cells. The true monocytic leukemias, acute monocytic leukemia (AMOL) and acute myelomonocytic leukemia (AMMOL), are closely related to acute myelocytic leukemia (AML) morphologically and by their response to chemotherapy. like AML, the leukemic cells from the AMMOL and AMOL patients form leukemic clusters in semisolid media. Cytochemical staining of leukemic cells for nonspecific esterases, presence of Fc receptor on the cell surface, phagocytic ability, low TdT activity, presence of surface "ruffles" and "ridges" on scanning EM, elevations of serum lysozyme, and clinical manifestations of leukemic tissue infiltration are features which accompanied monocytic differentiation in these cases.

Topics: Adolescent; Adult; Aged; Blood Cells; Bone Marrow; Female; Hodgkin Disease; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Large B-Cell, Diffuse; Male; Microscopy, Electron, Scanning; Middle Aged; Muramidase

A series of 55 biopsies from different types of malignant lymphomas were characterized in short-term culture experiments and during prolonged growth in vitro. The majority of the lymphocytic lymphomas and half of the histiocytic lymphomas expressed surface immunoglobulin, either in monoclonal or polyclonal form, indicating B-lymphocyte derivation. No lysozyme production was noted in either type of lymphoma, giving further support to the notion that histiocytic lymphomas are not truly histiocytic. Production of beta2-microglobulin was higher in histiocytic than in lymphocytic lymphoma and Hodgkin's disease but did not significantly differ from the production observed in non-neoplastic lymph node disorders. Incorporation of 3H-thymidine varied greatly within each category of lymphoma; the highest mean labelling index was noted in histiocytic lymphoma, possibly reflecting the generally more malignant course in such cases. Epstein-Barr virus-associated nuclear antigen was observed in one case of Hodgkin's disease. Attempts to establish permanent tumor cell lines were successful only from two explants of lymphocytic lymphoma and one pleural effusion from histiocytic lymphoma. The two cell lines derived from lymphocytic lymphomas both exhibited B-lymphocyte characteristics. The histiocytic lymphoma line lacked lymphocyte markers, produced lysozyme and was found to be rich in cytoplasmic esterases. These features are consistent with a "true" histiocytic derivation of this line. Lymphoblastoid cell lines representing non-neoplastic EBV-carrying lymphocytes contaminating the biopsies were derived from 19 biopsies, with the highest frequency noted in cultures of biopsies from Hodgkin's disease. The tumor lines were all EBV-genome negative.

Topics: Antigens, Viral; beta 2-Microglobulin; Biopsy; Cell Line; Cells, Cultured; DNA, Neoplasm; Herpesvirus 4, Human; Hodgkin Disease; Humans; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Muramidase; Receptors, Antigen, B-Cell

Four murine monocyte, myelomonocyte, and histiocyte or macrophage tumor cell lines adapted to culture were growth inhibited by one or more of the following macrophage-activating substances: Mycobacterium bovis, Bacillus Calmette-Guérin strain, zymosan, lipopolysaccharide, and dextran sulfate, as well as tuberculin purified protein derivative, but not latex beads. Lipopolysaccharide was effective with one line at 4 ng/ml. All four lines actively phagocytosed zymosan and latex beads. In many cases the growth inhibition was apparently immediate but only cytostatic, and cell proliferation resumed upon removal of the drug. Bacillus Calmette-Guérin, live or boiled, was toxic to some of the tumor lines. Synthesis of lysozyme by all the cell lines in the monocyte series and production of granulocyte colony-stimulating factor by the myelomonocytic leukemia were not inhibited during several days of zero growth conditions in the presence of drugs. Since these agents had no direct effect on other hematopoietic tumor types (myeloma, T-lymphoma, mastocytoma) at the same or up to 10(4) higher concentrations, it is proposed that the sensitive tumors retain specific receptors for immunostimulants, either at the cell surface or within the cell in the case of phagocytosable particles. The binding of these agents to physiological receptors leads to stimulation and mitogenesis in normal macrophages and lymphocytes but leads to growth inhibition without affecting differenetiated functions in the corresponding tumor lines.

Topics: Adjuvants, Immunologic; BCG Vaccine; Cell Division; Cell Survival; Cells, Cultured; Dextrans; Latex; Leukemia, Myeloid; Lipopolysaccharides; Lymphocyte Activation; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Microspheres; Monocytes; Muramidase; Mycobacterium bovis; Neoplasms, Experimental; Tuberculin; Zymosan

Lysozyme activity was studied in blood smears, serum, and urine of patients suffering from leukaemia or other haematological diseases. Increased enzyme activity was found in myelocytic, myelomonocytic and monocytic leukaemia and equally in secondary granulocytosis and polycythaemia vera. Reduced rates were found in lymphocytie leukaemia, malignant lymphoma with bone marrow involvement, and myelophthisic conditions. A rise in urinary lysozyme occurred when the serum level exceeded 50 microgram/ml. Abundant activities were found in myelomonocytic and monocytic leukaemias. Using the bacteriolytic method in blood smears, no enzyme activity was demonstrated in cells of acute or chronic lymphocytic leukaemia, in monocytic leukaemia however, almost all cells show strong reaction. In acute myelocytic or myelomonocytic leukaemia, the portion of positive cells changes from case to case depending on the degree of cell differentiation and maturation. In chronic myelocytic leukaemia there was no difference as compared to enzyme activity of myelocytes in bone marrow of control cases. Thus the bacteriolytic demonstration of lysozyme in blood smears may additionally contribute to distinction of different types of blastic leukaemias, and serum lysozyme also may allow more reliable insight into granulocytic and monocytic myelopoiesis than morphologic studies of blood or bone marrow smears can do, e.g. in agranulocytosis and pancytopenia.

Topics: Anemia, Aplastic; Hematologic Diseases; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Muramidase; Waldenstrom Macroglobulinemia

A human hematopoietic cell line (U-937) with exceptional characteristics was derived from a patient with generalized histiocytic lymphoma. The morphology of the cell line was identical to that of the tumor cells in the pleural effusion from which the line was derived. Since Epstein-Barr virus (EBV) carrying diploid lymphoblastoid cell lines unrelated to the tumor population often become established in vitro from non-Burkitt lymphoma explants, several parameters were studied to discriminate the U-937 from such lines: morphology in vitro, growth characteristics, cytochemistry, surface receptor pattern, Ig production, lysozyme production, beta2-microglobulin production, presence of EBV genome and karyotype. In all these respects U-937 differed from prototype lymphoblastoid cell lines. The histiocytic origin of the cell line was shown by its capacity for lysozyme production and the strong esterase activity (naphtol AS-D acetate esterase inhibited by NaF) of the cells. It is therefore concluded that the U-937 is a neoplastic, histiocytic cell line.

Topics: Adult; beta 2-Microglobulin; Cell Division; Cell Line; Cells, Cultured; Culture Media; Herpesvirus 4, Human; HLA Antigens; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Muramidase; Phagocytosis; Receptors, Antigen, B-Cell

Infusion of cycloheximide i.v., an antibiotic known to inhibit synthesis of protein, at a rate of 0.2 mg/kg/hr, reliably caused lysis of fever in 15 chronically febrile patients with Hodgkin's disease who did not have detectable bacterial, fungal, or viral infection. Antipyretic effects were also seen in some patients with reticulum cell sarcoma, lymphosarcoma, acute leukemia, histiocytic medullary reticulosis, plasma cell myeloma, carcinoma of the lung, and carcinoma of the cervix. The drug failed to produce defervescence in four patients with normal granulocyte reserves, who were febrile due to bacterial infection. When infused at a rate of 0.2 mg/kg/hr, the drug apparently caused an acute alteration of protein metabolism in man in that plasma amino acid nitrogen rose acutely while plasma levels of muramidase and ribonuclease fell during the period of the infusion. The data suggest that continuing synthesis of protein may be involved in nonbacterial fever of neoplastic disease. Mammalian granulocytes and monocytes are known to elaborate a pyrogenic protein following appropriate stimulation; it is suggested that in some types of neoplastic disease, particularly Hodgkin's disease, tumor cells may produce and release a pyrogenic protein and that drug-induced inhibition of its synthesis is responsible for the observed lysis of fever.

Topics: Bacterial Infections; Cycloheximide; Female; Fever; Hodgkin Disease; Humans; Leukemia; Lung Neoplasms; Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Muramidase; Neoplasm Proteins; Neoplasms; Nitrogen; Ribonucleases; Uterine Cervical Neoplasms

Topics: Brain Neoplasms; Cerebrospinal Fluid; Female; Glioma; Histiocytosis, Langerhans-Cell; Humans; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Male; Meningitis; Muramidase; Neoplasm Metastasis

Topics: Bacterial Infections; Diabetes Mellitus; Hodgkin Disease; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukocytes; Lymphoma, Large B-Cell, Diffuse; Muramidase

Topics: Acetates; Alkaline Phosphatase; Biopsy; Blood Cell Count; Blood Proteins; Bone Marrow; Chlorine; Chronic Disease; Clinical Enzyme Tests; Diagnosis, Differential; Esterases; Humans; Leukemia; Lymphatic Diseases; Lymphoma, Large B-Cell, Diffuse; Monocytes; Muramidase; Neutrophils; Primary Myelofibrosis; Reticulocytes

A transplantable mouse tumor, GPC-11, produces large amounts of lysozyme. The tumor is a reticulum cell sarcoma, type A, and is a neoplasm of monocytes. The lysozyme was purified from mouse urine in quantities sufficient for structural analysis. Comparison of mouse lysozyme with lysozymes from; chicken egg white and patients with monocytic leukemia reveals similarities in size and electrophoretic mobility and, with human lysozyme, in functional properties; but considerable differences are found in antigenic characteristics and amino acid composition.

Topics: Animals; Chromatography, Ion Exchange; Egg White; Electrophoresis; Humans; Hydrogen-Ion Concentration; Leukemia, Myeloid; Lymphoma, Large B-Cell, Diffuse; Mice; Monocytes; Muramidase; Ultracentrifugation

Topics: Adult; Anemia, Aplastic; Child; Hematologic Diseases; Hodgkin Disease; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemoid Reaction; Lymphoma; Lymphoma, Large B-Cell, Diffuse; Lymphoma, Non-Hodgkin; Multiple Myeloma; Muramidase; Mycosis Fungoides; Myeloproliferative Disorders; Polycythemia Vera

Topics: Adult; Dysgerminoma; Esophageal Neoplasms; Female; Herpes Zoster; Humans; Lymphoma, Large B-Cell, Diffuse; Male; Middle Aged; Muramidase; Radiotherapy; Testicular Neoplasms