muramidase and Leukemia--Myeloid--Acute

The possible role of DNA methylation changes during several commitment steps of immature myeloid precursor cells toward functional, terminally differentiated phagocyte cells has previously been examined in the human myeloperoxidase (MPO) and macrophage colony-stimulating factor/c-fms genes using normal and transformed myeloid precursor cells. The human lysozyme (LZM) gene also provides a very useful model, because its protein synthesis is continuously increased during myelopoiesis and thus most abundant in mature phagocytes. Several shifts toward LZM gene demethylation coincide with upregulation of expression: activation of expression in myeloid precursor cells and in primary cells of acute myeloid leukemia (AML) was associated with demethylation at a CpG dinucleotide within the 5' flanking region; high-level expression in different types of normal mature phagocytic cells was associated with complete demethylation at two additional, intragenic CpG sites. Methylation changes occurring within the lysozyme gene could reflect transcriptional control of gene expression or maintenance of distinct maturation stages during phagocyte development. They correlate with maturational arrest and lysozyme gene expression in acute myeloid leukemias and may thus provide a genetic marker for the blocked differentiation of these neoplastic cells. Similar observations have been made for the MPO and c-fms genes.

Topics: Cytosine; Dinucleoside Phosphates; DNA Methylation; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Hematopoiesis; Hematopoietic Stem Cells; Humans; Leukemia, Myeloid, Acute; Muramidase; Peroxidase; Phagocytes; Transcription, Genetic

Topics: Cell Differentiation; Cell Division; Cytokines; Gene Expression Regulation, Leukemic; Humans; Lactoferrin; Leukemia, Myeloid, Acute; Muramidase; Myeloblastin; Peroxidase; Serine Endopeptidases

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Bone Marrow Cells; Cerebral Hemorrhage; Daunorubicin; Female; Gastrointestinal Hemorrhage; Glucuronidase; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Middle Aged; Monocytes; Muramidase; Naphthol AS D Esterase; Periodic Acid-Schiff Reaction; Peroxidases; Pregnancy; Prognosis; Remission, Spontaneous

Topics: Anemia, Aplastic; Animals; Bacteriological Techniques; Bone Marrow; Glomerular Filtration Rate; Histological Techniques; Humans; Hypersplenism; Immunologic Techniques; Iodine Radioisotopes; Kidney; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Neutrophils; Phosphorus Radioisotopes; Polycythemia Vera; Rabbits

Topics: Cytarabine; Evaluation Studies as Topic; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Methods; Muramidase; Neutrophils; Thioguanine

Topics: Acute Disease; Aged; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Middle Aged; Muramidase; Remission, Spontaneous

Topics: Acute Kidney Injury; Animals; Body Fluids; Cell Wall; Clinical Enzyme Tests; Humans; Hydrolysis; Immunodiffusion; Kidney Diseases; Kidney Tubules; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Micrococcus; Molecular Weight; Muramidase; Rats; Spectrophotometry

Myeloid sarcoma (MS) is defined as an extramedullary mass-forming lesion composed of immature myeloid cells. It is a rare but well-known manifestation of acute myeloid leukemia. Pediatrics testicular MS may pose a possible diagnostic challenge, an issue that is underscored in the few testicular pediatric MS cases reported in the literature. Herein, we report a series of 5 cases of pediatric testicular MS that are evaluated at the morphologic and immunohistochemical levels with correlation with the KMT2A (MLL) rearrangement status. Three patients presented with no prior history of acute myeloid leukemia. All 5 cases showed monoblastic morphology; positive for CD33, CD43, CD68, CD163, CD4 (dim), and lysozyme; and negative for CD10, CD34, CD117, and myeloperoxidase. KMT2A (MLL) rearrangement was detected in 4 of the 5 cases. In the literature, 8 more cases of pediatric testicular lymphoma were reported. Most of them showed monocytic differentiation and KMT2A (MLL) rearrangement was reported in 3 of the cases. In conclusions, testicular MS in pediatric patients shows monoblastic differentiation which may be attributed to the KMT2A (MLL) rearrangement. We also highlight the importance of using an extended immunohistochemistry panel in the diagnosis of MS.

Topics: Antigens, CD; Antigens, CD34; Antigens, Differentiation, Myelomonocytic; CD4 Antigens; Child; Child, Preschool; Gene Rearrangement; Histone-Lysine N-Methyltransferase; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Infant; Leukemia, Myeloid, Acute; Leukosialin; Male; Muramidase; Myeloid-Lymphoid Leukemia Protein; Neprilysin; Peroxidase; Proto-Oncogene Proteins c-kit; Receptors, Cell Surface; Sarcoma, Myeloid; Sialic Acid Binding Ig-like Lectin 3; Testicular Neoplasms

A 2-year-old, female German Shepherd Dog with facial nerve paralysis was diagnosed with acute myelomonocytic leukemia based on clinical, cytologic, and immunologic findings. Proteinuria (urine proteincreatinine ratio = 1.5) occurred in the absence of renal failure. Qualitative assessment of proteinuria by sodium dodecyl sulfate-agarose gel electrophoresis revealed a broad band with a molecular weight of approximately 15 kDa that was compatible with lysozyme (LZM). A diagnosis of tubular proteinuria was made, and a chemical evaluation of LZM in serum and urine samples was performed using a turbidimetric assay. The LZM concentrations were 24.5 mg/l (reference interval: 2.5-8.0 mg/l) and 274.5 mg/l (reference interval: <2 mg/l) in serum and urine, respectively.

Topics: Animals; Dog Diseases; Dogs; Female; Leukemia, Myeloid, Acute; Muramidase; Proteinuria

Topics: Aged; Antigens, CD; Antigens, Differentiation, Myelomonocytic; Biomarkers, Tumor; Bone Neoplasms; Carboxylic Ester Hydrolases; Humans; Leukemia, Myeloid, Acute; Magnetic Resonance Imaging; Male; Muramidase; Neoplasms, Multiple Primary; Peroxidase; Sarcoma, Myeloid; Skin Neoplasms; Soft Tissue Neoplasms; Subcutaneous Tissue

The AML1 (RUNX1)-MTG8 (ETO) fusion transcription factor generated by the t(8;21) translocation is believed to deregulate the expression of genes that are crucial for normal differentiation and proliferation of hematopoietic progenitors, resulting in acute myelogenous leukemia. To elucidate the role of AML1-MTG8 in leukemogenesis, we used oligonucleotide microarrays to detect alterations in gene expression caused by ectopic expression of AML1-MTG8 in a murine myeloid progenitor cell line, L-G. Microarray analysis of approximately 6500 genes identified 32 candidate genes under the downstream control of AML1-MTG8. Among the 32 genes, 23 were not known to be regulated by AML1-MTG8. These included many granule protein genes and several cell surface antigen genes. Interestingly, AML1-MTG8 enhanced the expression of several genes that are usually induced during granulocytic differentiation, particularly those encoding azurophil granule proteins, including cathepsin G, myeloperoxidase and lysozyme. This indicates that AML1-MTG8 induces partial differentiation of myeloid progenitor cells into promyelocytes in the absence of the usual differentiation signals, while it inhibits terminal differentiation into mature granulocytes. Thus, AML1-MTG8 itself may play a crucial role in defining a unique cytologic type with abnormal maturation, characteristic of t(8;21) acute myelogenous leukemia.

Topics: Acute-Phase Proteins; Animals; Case-Control Studies; Cathepsin G; Cathepsins; Cell Differentiation; Cell Line; Chromosomes, Human, Pair 21; Chromosomes, Human, Pair 8; Core Binding Factor Alpha 2 Subunit; Gene Expression Profiling; Gene Expression Regulation; Granulocytes; Humans; Leukemia, Myeloid, Acute; Lipocalin-2; Lipocalins; Mice; Muramidase; Myeloid Progenitor Cells; Oligonucleotide Array Sequence Analysis; Oncogene Proteins; Oncogene Proteins, Fusion; Peroxidase; Proto-Oncogene Proteins; RUNX1 Translocation Partner 1 Protein; Serine Endopeptidases; Transcription Factors; Transduction, Genetic; Translocation, Genetic

Serum concentrations of hepatocyte growth factor (HGF) were measured in 60 patients suffering from acute myelocytic leukaemia (AML). At the time of diagnosis elevated HGF concentrations (> 1.25 ng/ml) were found in 28% of the patients. HGF levels correlated with the presence of disseminated intravascular coagulation (DIC), levels of lysozyme, creatinine, peripheral blood blast counts and lactic dehydrogenase. In the group of patients with high HGF (>1.25 ng/ml) we found a tendency towards an increased early mortality; 41% of them died within 15 d from diagnosis, as opposed to 5% of the patients with normal HGF (log rank test p=0.07). DIC-related bleeding or thrombosis contributed to this early mortality. In responders, HGF levels normalized after treatment. HGF levels are low in neutropenia and neutropenic infections.

Topics: Biomarkers, Tumor; Blood Cell Count; Creatinine; Disseminated Intravascular Coagulation; Hepatocyte Growth Factor; Humans; L-Lactate Dehydrogenase; Leukemia, Myeloid, Acute; Muramidase; Survival Analysis

Mouse monocytic Mm-A, Mm-P, Mm-S1, and Mm-S2 cells are sublines of mouse monocytic and immortalized Mm-1 cells derived from spontaneously differentiated, mouse myeloblastic M1 cells. Although these subline cells retain their monocytic characteristics in vitro, Mm-A and Mm-P cells are highly leukemogenic to syngeneic SL mice and athymic nude mice, whereas Mm-S1 and Mm-S2 cells are not or are only slightly leukemogenic. To better understand the molecular mechanisms of these levels of leukemogenicity, we investigated putative leukemogenesis-associated genes or oncogenes involved in the maintenance of growth, especially in vivo, by means of differential mRNA display. We isolated a fragment clone (15T01) from Mm-P cells. The mRNA probed with 15T01 was expressed at high levels in leukemogenic Mm-P and Mm-A cells but not in nonleukemogenic Mm-S1 and Mm-S2 cells. The gene corresponding to 15T01, named TRA1, was isolated from an Mm-P cDNA library. The longest open reading frame of the TRA1 clone predicts a peptide containing 204 amino acids with a calculated molecular weight of 23,049 D. The predicted TRA1 protein is cysteine-rich and contains multiple cysteine doublets. A putative normal counterpart gene, named NOR1, was also isolated from a normal mouse kidney cDNA library and sequenced. NOR1 cDNA predicts a peptide containing 234 amino acids. The sequence of 201 amino acids from the C-terminal NOR1 was completely identical to that of TRA1, whereas the remaining N-terminal amino acids (33 amino acids) were longer than that (3 amino acids) of TRA1 and the N-terminus of NOR1 protein contained proline-rich sequence. A similarity search against current nucleotide and protein sequence databases indicated that the NOR1/TRA1 gene(s) is conserved in a wide range of eukaryotes, because apparently homologous genes were identified in Caenorhabditis elegans and Saccharomyces cerevisiae genomes. Northern blotting using TRA1-specific and NOR1-specific probes indicated that TRA1 mRNA is exclusively expressed in leukemogenic but not in nonleukemogenic Mm sublines and normal tissues and also indicated that NOR1 mRNA is expressed in normal tissues, especially in kidney, lung, liver, and bone marrow cells but not in any Mm sublines. After leukemogenic Mm-P cells were induced to differentiate into normal macrophages by sodium butyrate, the normal counterpart, NOR1, was expressed, whereas the TRA1 level decreased. Furthermore, transfection of TRA1 converted nonleukemogenic Mm-S1 cel

Topics: Amino Acid Sequence; Animals; Base Sequence; Caenorhabditis elegans; Carrier Proteins; Cell Transformation, Neoplastic; Cloning, Molecular; DNA-Binding Proteins; DNA, Complementary; Evolution, Molecular; Fungal Proteins; Gene Expression Regulation, Leukemic; Genes; Helminth Proteins; Leukemia, Myeloid, Acute; Membrane Proteins; Mice; Mice, Inbred Strains; Molecular Sequence Data; Monocytes; Muramidase; Neoplasm Proteins; Neoplasm Transplantation; Nerve Tissue Proteins; Nuclear Proteins; Organ Specificity; Phospholipid Transfer Proteins; Polymerase Chain Reaction; Proteins; Receptors, Steroid; Receptors, Thyroid Hormone; RNA, Messenger; RNA, Neoplasm; Saccharomyces cerevisiae; Sequence Alignment; Sequence Homology, Amino Acid; Species Specificity; Subtraction Technique; Transfection; Tumor Cells, Cultured

The revised French-American-British (FAB) classification system for acute myeloid leukemia (AML) recommends the determination of serum lysozyme (SL) or urine lysozyme (UL) levels as an aid in distinguishing acute myeloblastic leukemia with maturation (FAB M2) from acute myelomonocytic leukemia (M4). We reviewed retrospectively 208 cases of adult leukemia in which SL and/or UL were obtained. Elevated lysozyme levels were not found in any of the M0, M3, or M7 cases, but were increased (false positive) in three (14%) M1 cases, 18 (19%) M2 cases and one (20%) M6 case. Although a UL value in excess of 3x normal was found in most cases of AML M4 and M5, only five (11%) M4 cases and three (20%) M5 cases had SL elevations of this magnitude. Lysozyme levels need to be interpreted in conjunction with other parameters for FAB classification.

Topics: Aged; Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Megakaryoblastic, Acute; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Promyelocytic, Acute; Male; Middle Aged; Muramidase

Using an ultrastructural immunogold method, we performed a quantitative study on cellular lysozyme (LZ) content in young normal bone marrow cells and in 14 cases of acute myeloid leukaemia (AML) of the M2, M3, M4 and M5 types. In five cases of M2 we found significantly lower LZ content than in normal promyelocytes and than in nine cases of M3, M4 and M5. In M3, M4 and M5 cells a very high LZ content was observed whereas the serum LZ activity was high in M4 and M5 and normal in M3. The intragranular LZ content was especially high in M5 and in most granules of M4 cells. The immunogold reaction (IGR) for LZ was also performed in cells previously reacted for myeloperoxidase (MPO). In M2 the granules showed definite positive MPO reactivity and low LZ density (granulocytic pattern), whereas in M5 we found high granular LZ content and weak or almost negative MPO activity (monocytic pattern). In M4 we found 'granulocytic' and 'monocytic' type of granules in the same cell. The IGR for LZ performed in post-embedded M5 cells which were previously subjected to phagocytosis of latex particles, showed granules that had moved toward the phagosome, releasing LZ without degranulation. The above findings and those showing normal serum LZ in M3 despite their high cellular LZ content, definitely indicate that only leukaemic M4 and M5 cells secrete LZ into their environment, explaining the high serum LZ observed in those leukaemias.

Topics: Acute Disease; Bone Marrow; Gold Colloid; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukemia, Myelomonocytic, Acute; Leukemia, Promyelocytic, Acute; Microscopy, Electron; Muramidase; Peroxidase; Phagocytosis

Protein kinase activities are involved in cellular proliferation and differentiation, and inhibitors of these activities are useful for studying the mechanisms of induction of differentiation. We found that staurosporine, an inhibitor of protein kinase activities, induced morphological differentiation of human myeloblastic leukemia ML-1 cells along myelomonocytic lineage and also induced functional differentiation (increase in nitroblue tetrazolium-reducing and lysozyme activities) in the cells. Several other protein kinase inhibitors such as 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7), sphingosine, N-(6-aminoethyl)-5-chloro-1-naphthalenesulfonamide and 1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine hydrochloride (ML-9) did not induce the differentiation of ML-1 cells. Treatment with staurosporine induced formation of granules in ML-1 cells, and the granules showed metachromasia by toluidine blue staining; however, histamine content did not increase. The "metachromatic" ML-1 cells were positive for CD14, indicating that staurosporine induced the differentiation of ML-1 cells into metachromatic monocytes/macrophages, 1 alpha,25-dihydroxyvitamin D3 (VD3) enhanced appearance of metachromatic granules in staurosporine-treated cells. These results suggest that modulation of protein phosphorylation by a staurosporine-sensitive protein kinase(s) may be associated with differentiation of ML-1 leukemia cells.

Topics: Alkaloids; Cell Differentiation; Cytoplasmic Granules; Histamine; Humans; Leukemia, Myeloid, Acute; Macrophages; Microscopy, Electron; Monocytes; Muramidase; Nitroblue Tetrazolium; Oxidation-Reduction; Protein Kinase Inhibitors; Staining and Labeling; Staurosporine; Tolonium Chloride; Tumor Cells, Cultured

The occurrence of opportunistic pathogens and the concentration of some antimicrobial factors in the oral cavity of both acute and chronic leukaemia patients were studied. Enterobacteria were isolated from both dental plaque and crevicular fluid of all the groups examined, with few differences between healthy volunteers and leukaemic subjects; yeasts were found in both the crevicular fluid and the dental plaque samples of chronic leukaemia patients, but only in the plaque of healthy volunteers. Acute leukaemia patients did not have yeasts, but they were the only group colonized by the pseudomonads. IgA and N-acetyl-D-glucosaminidase (NAGase) significantly increased in chronic leukaemia patients compared with controls, whilst lysozyme seemed to present no marked differences for all groups. A further increase in NAGase concentration and an elevation in lysozyme content of saliva was observed for chronic leukaemia patients with severe periodontal lesions.

Topics: Acetylglucosaminidase; Dental Plaque; Enterobacteriaceae; Gingival Crevicular Fluid; Humans; Immunoglobulin A; Leukemia, Myelogenous, Chronic, BCR-ABL Positive; Leukemia, Myeloid, Acute; Mouth; Muramidase; Opportunistic Infections; Precursor Cell Lymphoblastic Leukemia-Lymphoma; Pseudomonas; Saliva; Yeasts

According to criteria established by the French-American-British (FAB) classification, a diagnosis of acute myelomonoblastic leukemia (FAB M4) is based on the presence of 20% bone marrow monocytes or a serum lysozyme level that exceeds the reference value by three times. Reported here is a case of acute myelogenous leukemia with eosinophilia and a cytogenetic inversion of chromosome 16 (inv 16) that lacks morphologic, cytochemical, and immunophenotypic features of monocytic differentiation, but which is associated with an elevated serum lysozyme value. The authors used an immunoelectron microscope to localize lysozyme to both normal and abnormal eosinophil granules, in addition to the secondary granules of myeloid precursors and monocytes. This enzyme could not be demonstrated within the myeloblasts of the patient studied. Postfixation with osmium tetroxide greatly reduced the staining intensity within the crystalloids of normal eosinophils, but only minimally affected that of monocytes, neutrophils, normal eosinophil granule matrix, and the abnormal granules of the leukemic eosinophils. These results demonstrate that lysozyme is present in both normal and leukemic eosinophils and that elevation of serum lysozyme in patients with acute myelogenous leukemia with eosinophilia is not a reliable indicator of monocytic differentiation. Furthermore, an occasional case of acute leukemia with inv 16 is classifiable as acute myelogenous leukemia with differentiation (FAB M2).

Topics: Adult; Bone Marrow; Eosinophilia; Eosinophils; Flow Cytometry; Histocytochemistry; Humans; Leukemia, Myeloid, Acute; Male; Microscopy, Electron; Microscopy, Immunoelectron; Muramidase

An unusual case of granulocytic sarcoma with a large retro-orbital tumor mass is described. The tumor had an uncommon cytomorphology and ultrastructure that mimicked a signet ring cell lymphoma. It was negative by chloroacetate esterase (CAE) stain. The patient was treated successfully with CHOP-regimen polychemotherapy and irradiation. Seventeen months after the initial diagnosis of malignant lymphoma, acute myeloid leukemia developed. Additional immunohistochemistry, including an immunoperoxidase staining for lysozyme, clearly demonstrated the early myeloid nature of the original tumor. This case emphasizes the importance of staining for lysozyme and other myeloid markers in addition to CAE staining in cases that demonstrate unusual morphological features.

Topics: Carboxylic Ester Hydrolases; Humans; Immunohistochemistry; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Microscopy, Electron; Middle Aged; Muramidase; Nasopharyngeal Neoplasms

We studied differentiation inducing effects of retinoic acid (RA), 1 alpha, 25-dihydroxyvitamin D3 (D3) and interferons (IFNs), alone and in combination, on fresh myeloid leukemic cells from 8 patients. RA not only induced the differentiation of leukemic cells in 5/8 cases, but potentiated differentiation by IFNs either in granulocytic or monocytic pathways. In particular, interferon-alpha enhanced granulocytic differentiation and interferon-gamma induced mono-macrophage differentiation of promyelocytic leukemic cells in the presence of RA. Differentiation induced by D3, alone or in combination with IFNs, was limited in all cases. RA plus IFNs might be an effective combination for differentiation therapy for some types of myeloid leukemia.

Topics: Cell Differentiation; Cholecalciferol; Esterases; Humans; Interferon Type I; Interferon-gamma; Leukemia, Myeloid, Acute; Muramidase; Nitroblue Tetrazolium; Tretinoin; Tumor Cells, Cultured

Topics: Chromatography, High Pressure Liquid; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Muramidase; Nephelometry and Turbidimetry

Leukemia cutis was documented by biopsy in 18 of 877 patients (2%) with acute myelogenous leukemia (AML) seen at Roswell Park Memorial Institute (Buffalo, NY) between 1969 and 1986. French-American-British (FAB) types included four M2, one M3, ten M4, and three M5. Lysozyme was more consistently detectable in skin sections in our cases than Leu-M1, alpha-1-antitrypsin, alpha-1-antichymotrypsin, or chloroacetate esterase activity. Additional extramedullary sites of involvement were present in 16 patients, including meningeal leukemia in six. Two patients had leukemia cutis preceding bone marrow leukemia. Skin was the initial site of relapse in 11 patients, without marrow relapse, occurring as late as 5.5 years after diagnosis. Most patients in this retrospective series were treated with radiation therapy and/or palliative chemotherapy, and did poorly, with prompt bone marrow relapses and serial skin relapses. Long-term disease-free survival was achieved in the one patient whose skin relapse was treated with whole-body electron-beam radiation therapy in conjunction with reinduction and consolidation chemotherapy. Severe skin toxicity was caused by administration of Adriamycin (doxorubicin) 12 days after electron-beam irradiation in one patient, but was not seen when cytosine arabinoside was administered in doses up to 3 g/m2 in conjunction with radiation therapy. This retrospective review suggests that optimal management of AML involving skin might include whole-body electron-beam irradiation in conjunction with induction or reinduction chemotherapy without anthracyclines, followed by consolidation chemotherapy. Additionally, there should be ongoing surveillance for and treatment of extramedullary disease at other sites, including the meninges.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Antigens, Differentiation, Myelomonocytic; Humans; Leukemia, Myeloid, Acute; Muramidase; Naphthols; Skin Neoplasms

The effect of calcitriol on the induction of differentiation in human promyelocytic leukemic cell line (HL-60) cultured in serum-free chemically defined medium (SFM) was investigated. The utilization of SFM containing RPMI-1640 basal medium supplemented with insulin (5 micrograms/ml), transferrin (5 micrograms/ml), sodium selenite (5 ng/ml), and bovine serum albumin (0.5 micrograms/ml), transferrin examination of the cellular/molecular mechanism of calcitriol's action in HL-60 cell differentiation without interference of components present in serum. HL-60 cells grown in SFM were induced to differentiate into monocytes/macrophages by calcitriol as indicated by induction of differentiation-associated biological and biochemical parameters: chemiluminescent (CL) responsiveness, lysozyme activity, nonspecific esterase, expression of cell surface antigens, and reduced proliferation. The exposure of HL-60 cells in SFM to calcitriol (from 10(-10) to 10(-8)M) resulted in dose-dependent induction of these parameters, which was similar to those obtained with cells grown in 10% fetal calf serum containing medium (10% SCM). However, calcitriol was 5-fold more potent for HL-60 cells cultured in SFM than those cultured in 10% SCM as indicated by shifts in dose-response curves for induction of CL responsiveness and lysozyme activity. The effect of calcitriol on the proliferation and acquisition of several monocyte-associated cell surface antigens was also more sensitive for HL-60 cells cultured in SFM than for cells grown in 10% SCM. We characterized and quantitated calcitriol receptors in HL-60 cells cultured in SFM in comparison to those in 10% SCM after exposing intact cells to radiolabeled calcitriol. Cells cultured in either SFM or 10% SCM exhibited calcitriol receptors that migrated at 3.4S as a single peak on sucrose gradients and elicited inherent DNA binding ability. There was essentially no difference in the apparent dissociation constants (Kd) nor in the number of calcitriol binding sites per HL-60 cell, that is approximately 6.0 X 10(-11) M and approximately 3000 binding sites/cell respectively. It is concluded that culturing HL-60 cells in SFM results in full expression of calcitriol-induced phenotypic changes excluding the possibility that such changes result from the indirect effect of calcitriol mediated by identified and/or unidentified components present in serum.

Topics: Calcitriol; Cell Differentiation; Cell Division; Cell Line; Culture Media; Esterases; Fluorescent Antibody Technique; Humans; Leukemia, Myeloid, Acute; Luminescent Measurements; Monocytes; Muramidase; Receptors, Calcitriol; Receptors, Steroid

92 patients with acute myeloid leukemia were classified according to the FAB classification (M1 n = 20, M2 n = 43, M3 n = 1, M4 n = 19, M5a n = 2, M5b n = 2, and M6 n = 5 patients). Serum measurements of lactoferrin (LF), myeloperoxidase (MPO) and lysozyme (LYS) were performed before the start of treatment. LF was significantly lower in M1 when compared with M2 but not as compared to M4, MPO was significantly higher in M2 and M4 than in M1, but comparable MPO levels were found in M2 and M4. LYS was significantly elevated in M2 in comparison with M1, and in M4 when compared to both M1 and M2. Polymorphonuclear granulocytes (PMNs) in M1 were significantly reduced when compared with M2 and M4, whereas mononuclear cells were significantly increased in M4 in comparison with both M1 and M2. FAB classification did not generate any prognostic information. When the patients were, instead, subdivided according to LF levels were found prognostically significant differences. Of patients below 100 micrograms/l, 44% went into remission as compared to 77% with LF from 101 to 400 micrograms/l. In patients with LF levels above 400 micrograms/l the remission frequency was only 14%. Multivariate statistical analysis on the data further suggested that lactoferrin may be used as an independent prognostic indicator. We conclude that although determination of the serum-levels of lactoferrin, lysozyme and myeloperoxidase in certain cases may be valuable as a supplement to the morphological examination of acute myeloid leukemia, it is evident that none of the three determinations can be used alone to distinguish between the FAB groups.

Topics: Adult; Aged; Female; Genetic Variation; Granulocytes; Humans; Lactoferrin; Lactoglobulins; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase; Peroxidase; Prognosis

Topics: Humans; Leukemia, Myeloid, Acute; Muramidase

Recently, a novel approach has been used in the treatment of leukemia: induction of the leukemic cells to undergo terminal differentiation. Based on its in vitro ability to induce differentiation in several myeloid leukemic cell lines, retinoic acid (RA) has been applied clinically in cases of myelodysplastic syndromes and acute myeloid and promyelocytic leukemia. In the present study we have determined in detail the ability of RA to induce expression of granulocytic functions in a human promyelocytic leukemia cell line (HL-60) and compared it with that of dimethylsulfoxide (DMSO). Several granulocytic characteristics (phagocytosis, surface adherence and generation of free radicals in response to phorbol-ester) were induced to the same degree by both agents. Other normal neutrophil functions, including lysozyme accumulation, spontaneous migration, chemotactic activity toward zymosan-activated serum (containing C5a), the peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) and spontaneous motility in semi-solid medium were induced by DMSO, but they were absent or incompletely expressed in RA-induced cells. In contrast, only RA induced migration toward leukotriene B4 (LTB4). Simultaneous treatment with RA and DMSO proved synergistic with respect to morphological maturation and several functions (e.g. NBT reduction), but complementary stimulation of other activities (e.g. chemotaxis, lysozyme content) could not be demonstrated. Furthermore, characteristics induced by DMSO (i.e., expression of C5a and FMLP receptors and accumulation of lysozyme) were inhibited by the addition of RA.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Cell Adhesion; Cell Differentiation; Cell Line; Dimethyl Sulfoxide; Granulocytes; Humans; Kinetics; L-Lactate Dehydrogenase; Leukemia, Myeloid, Acute; Muramidase; Neutrophils; Phagocytosis; Tretinoin

Serum levels of lactoferrin, lysozyme and myeloperoxidase were measured sequentially after induction treatment in 30 patients with AML in order to test the hypothesis that these proteins may be used to monitor activity and different stages of myelopoiesis in the bone-marrow. The results showed that myeloperoxidase and lysozyme started to rise again 6-8 days after initiation of treatment as compared to 12 d for lactoferrin and 16 d for blood polymorphonuclear leukocytes. The rate of marrow regeneration was exponential and estimated to be 9-20% per d. The comparison between two different chemotherapy regimes showed that the initial reduction in lysozyme, in contrast to other measured variables, was significantly larger with the therapy that contained vincristine and glucocorticosteroids. This might reflect a reduction in lysozyme secretion in addition to the effects on the leukemic cell mass. We conclude that the measurements of lactoferrin, lysozyme and myeloperoxidase in serum under certain circumstances may be used to monitor the myelopoietic activity in the bone-marrow.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Marrow; Cytarabine; Daunorubicin; Doxorubicin; Hematopoiesis; Humans; Lactoferrin; Lactoglobulins; Leukemia, Myeloid, Acute; Leukocyte Count; Muramidase; Neutrophils; Peroxidase; Prednisolone; Thioguanine; Time Factors; Vincristine

A non-competitive avidin-biotin immuno-enzymatic assay (NABA) for lysozyme is described. The assay was found to be more sensitive than a competitive assay with biotinylated lysozyme. The lower detection limit of NABA was 0.1 ng lysozyme/ml compared to 1 ng/ml for the competitive assay. The intra-assay and inter-assay coefficients of variation for NABA were 5.9 and 9.1%, respectively. The total time for NABA can be decreased (to less than 1 h) without influencing the detection limit or the analytical range. Serum lysozyme levels measured by NABA and the enzymatic assay in 32 samples showed a correlation coefficient of r = 0.97.

Topics: Avidin; Binding, Competitive; Biotin; Humans; Immunoenzyme Techniques; Leukemia, Myeloid, Acute; Muramidase; Nephelometry and Turbidimetry

Blood and bone marrow samples from 20 individuals with reactive conditions and 26 cases of acute and chronic myeloid leukemias were tested for the presence of lysozyme, alpha-1-antitrypsin (alpha-1-AT), and alpha-1-antichymotrypsin (alpha-1-ACT). We compared the reactivity of samples in smears, cytocentrifuge preparations, and paraffin sections. Lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin were found only in polymorphonuclear leukocytes and monocytes and their precursors. Lymphocytes, E-rosetting cells, Con A-activated lymphocytes, natural killer (NK) cells, red blood cells, erythroblasts, and megakaryocytes were consistently negative. Leukemic myeloblasts showed definite reactivity for both alpha-1-antitrypsin and alpha-1-ACT, but not for lysozyme. By contrast, lysozyme was present in poorly differentiated leukemic monoblasts, while alpha-1-antitrypsin and alpha-1-antichymotrypsin showed only weak reactivity. More mature myeloid and moncytic cells showed positive staining for all three antigens tested with differences in staining distribution and intensity. In four cases of chronic myeloid leukemia (CML), circulating mature polymorphonuclear leukocytes were deficient in both lysozymne and alpha-1-antitrypsin. The use of lysozyme, alpha-1-antitrypsin, and alpha-1-antichymotrypsin identifies normal and leukemic cells of the myeloid-monocytic series at all stages of maturation and is applicable to a variety of sample preparations.

Topics: alpha 1-Antichymotrypsin; alpha 1-Antitrypsin; Bone Marrow; Cell Separation; Chymotrypsin; Clinical Enzyme Tests; Flow Cytometry; Hematopoietic Stem Cells; Humans; Immunoenzyme Techniques; Killer Cells, Natural; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Microtomy; Monocytes; Muramidase; Paraffin

The human promyelocytic cell line HL-60, differentiates in response to a variety of agents including dibutyryl cAMP and agents which increase intracellular cAMP concentrations (phosphodiesterase inhibitors, PGE2, and cholera toxin). HL-60 is also known to be rich in H2 -histamine sensitive adenylate cyclase activity. The present study was therefore designed to test the effects of H2-stimulation on growth and differentiation of HL-60 using the potent H2 agonist dimaprit. Dimaprit markedly increased cAMP production in a dose-dependent manner reaching maximal levels after 30-60 minutes. Intracellular cAMP levels decreased thereafter and by 24 hours were approximately 2-3 fold increased above control. Intracellular cAMP levels were not altered by dimaprit (10(-7)M to 10(-4)M) at 4 days in culture compared to either untreated HL-60 cells or dimethylsulfoxide (DMSO) (1.3%) treated cells. While exponential growth was unaltered by dimaprit (10(-7)M to 10(-4)M) as compared to control, dimaprit induced i) morphologic maturation to the myelocyte and metamyelocyte form with no differentiation seen beyond the metamyelocyte even after 6 days in culture, ii) increased NBT reductase activity and iii) dose-dependent increase in lysozyme activity which could be completely blocked by cimetidine, a specific H2 antagonist. Dimaprit-induced differentiation of HL-60 cells was associated with an initial but transient increase in intracellular cAMP production. Maturation beyond the metamyelocyte stage was not observed. Acquisition of NBT reductase and lysozyme activity correlated with morphologic maturation.

Topics: Bone Marrow; Bone Marrow Cells; Bucladesine; Cell Differentiation; Cell Division; Cell Line; Cyclic AMP; Dimaprit; Dimethyl Sulfoxide; Granulocytes; Humans; Leukemia, Myeloid, Acute; Muramidase; Neutrophils; Nitroblue Tetrazolium; Oxidation-Reduction; Thiourea

The cultured mouse macrophage-like cell line Mm-1 synthesizes and secretes lysozyme continuously like normal macrophages. Culture of the cells in the presence of prostaglandin D2 for 3 days strongly inhibited their production of lysozyme activity. Prostaglandin D2 caused dose-dependent inhibition of the activity: 1 X 10(-6) M prostaglandin D2 caused about 50% inhibition. Inhibition by prostaglandin D2 was not related to cytotoxicity and was reversible. The rate of synthesis of lysozyme protein was measured by culturing Mm-1 cells with radioactive amino acids and then immunoprecipitating the protein. At the concentrations used, prostaglandin D2 inhibited the synthesis of lysozyme dose-dependently, but did not suppress the synthesis of total protein. Of the various types of prostaglandin, only prostaglandin D2 inhibited the production of lysozyme in Mm-1 cells. Moreover, prostaglandin D2 did not inhibit the production of other lysosomal enzymes, such as acid proteinase, acid phosphatase and beta-glucuronidase, and did not affect Fc receptors on the cell surface, adherence of cells to the culture dish or the cell morphology. These results indicate that prostaglandin D2 specifically inhibits the synthesis of lysozyme in Mm-1 cells. When Mm-1 cells were cultured for 3 days in the presence of the ethyl acetate extract from the culture medium in which Mm-1 cells had been cultured with prostaglandin D2 for 3 days, the production of lysozyme activity of Mm-1 cells was also markedly inhibited by the extract. After the incubation of prostaglandin D2 for 3 days with Mm-1 cells, less than 10% of the initial prostaglandin D2 remained and two major metabolites appeared. These results suggest that the metabolites of prostaglandin D2 were involved in the inhibitory action of prostaglandin D2 in Mm-1 cells.

Topics: Animals; Cell Line; Kinetics; Leukemia, Myeloid, Acute; Lysosomes; Macrophages; Mice; Muramidase; Prostaglandin D2; Prostaglandins D; Protein Biosynthesis

Serum lysozyme activity was measured in samples from 65 children with acute lymphatic and myelogenous leukemia, solid tumors and malignant lymphoma in comparison with 45 healthy children. All children with acute lymphatic leukemia (ALL) had significantly reduced levels of lysozyme before starting therapy compared with a control group (p less than 0,01). Children with ALL in complete remission had lysozyme levels comparable to normal children, while children with ALL in relapse showed pathological low levels again. Children with acute myelogenous leukemia (AML), solid tumors and malignant lymphomas had higher lysozyme concentration before therapy than healthy children. Determination of lysozyme activity in children with acute leukemia and malignant tumors is of value for diagnosis and to control the effect of therapy.

Topics: Child; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Muramidase; Neoplasms

We have investigated the control of lysozyme gene expression in HL-60 cells induced to differentiate into macrophage-like cells with phorbol myristate acetate (PMA). Differentiation, as evidenced by cellular adherence, and morphological changes corresponded temporally to an increase in nonspecific esterase activity. The lysozyme concentration in the medium of uninduced HL-60 cells was 10 micrograms/10(7) cells, increasing to a maximum of 46 micrograms/10(7) cells after 48 h incubation with PMA (16 nM). At 72 h the lysozyme concentration decreased to 16 micrograms/10(7) cells. Intracellular lysozyme activity remained constant throughout differentiation. If HL-60 cells were exposed to PMA for 24 h, washed, then maintained in normal medium, they differentiated normally, confirming their irreversible commitment to differentiate. The increase in lysozyme secretion by these cells, however, is markedly blunted suggesting that continued PMA treatment of differentiated cells is required for their secretion of lysozyme. There is no change in the rate of extracellular degradation of lysozyme during differentiation. The level of lysozyme mRNA does not correlate directly with the amount of lysozyme secreted into the medium. Hybridization of uninduced HL-60 cell RNA with a chicken lysozyme cDNA probe demonstrates moderate hybridization. There is a modest (five-fold) increase in lysozyme mRNA between 0 and 36 h of exposure to PMA, corresponding to the burst of lysozyme secretion by these cells. The lysozyme mRNA decreases to a level which is lower than the original baseline by 72 h, when the cells are still secreting substantial amounts of lysozyme. These data suggest that both transcriptional and post-transcriptional controls are operative in the control of lysozyme gene expression during the differentiation of HL-60 cells. They also imply that lysozyme secretion is not a necessary component in the macrophage-monocyte differentiation of these cells.

Topics: Animals; Cell Differentiation; Cell Line; Gene Expression Regulation; Humans; Leukemia, Experimental; Leukemia, Myeloid, Acute; Macrophages; Muramidase; RNA, Messenger; Tetradecanoylphorbol Acetate; Time Factors

This study reports the cytochemical, electrophoretic and immunological characteristics of blasts cells from 39 cases of acute myelomonocytic leukaemia (M4). The results indicate considerable cytochemical heterogeneity, particularly with respect to esterase (alpha naphthyl acetate and chloroacetate) activities and suggest that an increased serum lysozyme concentration is a more consistent feature. Investigations with a range of monoclonal antibodies also revealed some differences in expression of monocyte-associated determinants although it is considered that immunological assessments are more consistent than cytochemistry in the detection of monocytic blast cell components. Analysis of ANAE isoenzymes by isoelectric focusing was found to be of particular value in cases where interpretation of ANAE cytochemistry was difficult.

Topics: Antibodies, Monoclonal; Carboxylic Ester Hydrolases; Humans; Isoelectric Focusing; Isoenzymes; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Muramidase; Naphthol AS D Esterase; Peroxidases

Mouse monocytic Mm-A cells are a highly leukemogenic variant line of the monocytic and non-leukemogenic cell line Mm-1, which developed spontaneously from mouse myeloid leukemia M1 cells. Studies were made on whether Mm-A cells could be induced to differentiate further by agents that were effective for inducing differentiation of the parent M1 cells and other leukemic cells. Of the agents tested, butyrate, conditioned medium from concanavalin A-stimulated spleen cells, lipopolysaccharide (LPS) and N6,O2-dibutyryl adenosine 3'5'-cyclic-monophosphate (dbcAMP) significantly stimulated the lysozyme activity of Mm-A cells, which is one of the most characteristic biochemical markers of monocytes and macrophages. Butyrate was the most effective agent for increasing lysozyme production by Mm-A cells; culture with 0.5mM butyrate for 3 days increased lysozyme production by Mm-A cells about 50-fold. Inducers of M1 cell differentiation such as dexamethasone, 1 alpha,25-dihydroxyvitamin D3, arginase, and proteinous inducer did not increase the lysozyme activity. Butyrate also induced NBT reduction and stimulated other differentiation-associated functions, such as expressions of Fc receptors on the cell surface, immune phagocytosis and production of inducer for M1 cell differentiation. Its effect in stimulating differentiation of Mm-A cells was synergistic with that of dbcAMP or LPS. Incubation with butyrate inhibited the proliferation of Mm-A cells, about 0.3mM butyrate causing 50% inhibition. These results indicate that monocytic, leukemogenic Mm-A cells can be induced to differentiate further by butyrate and that the inducers of differentiation of Mm-A cells are markedly different from those of the parent myeloblastic M1 cells.

Topics: Animals; Butyrates; Cell Differentiation; Cells, Cultured; Culture Media; Drug Interactions; Enzyme Induction; Fatty Acids; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lipopolysaccharides; Mice; Muramidase; Phagocytosis; Receptors, Fc

The paper discusses the data on secretion of immunoglobulin and lysozyme in the upper respiratory tract of patients with acute leukemia. The data were used in the evaluation of certain biological preparations intended for prevention of infectious complications.

Topics: Bacterial Infections; Bacteriophages; Humans; Immunoglobulin A, Secretory; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Mucous Membrane; Muramidase; Pharynx; Pseudomonas aeruginosa; Staphylococcus Phages

A myeloid cell line, designated PL-21, was established from the peripheral blood of a patient with acute promyelocytic leukemia. The PL-21 cell line grew in single-cell suspension, with a doubling time of 48-64 hr, and consisted of promyelocytes with fine immature nuclei and prominent azurophilic granules in the cytoplasm. PL-21 cells were positive for peroxidase, naphthol AS-D chloroacetate esterase, and Sudan Black B staining. Under the usual culture conditions, a small proportion of these cells differentiated into mature granulocytes, and this differentiation was enhanced by the addition of dimethyl sulfoxide in the culture medium. PL-21 cells had receptors for the Fc portion of IgG and complement, intracytoplasmic lysozyme and phagocytic activity, but lacked Epstein-Barr virus-associated nuclear antigen. Chromosome analysis of this cell line revealed a human male polyploid karyotype with 13q+ and double minute chromosomes. This new myeloid cell line may provide useful material for the study of proliferation and differentiation of human leukemia cells.

Topics: Adult; Cell Differentiation; Cell Line; Cells, Cultured; Dimethyl Sulfoxide; Humans; Immunoenzyme Techniques; Karyotyping; Leukemia, Myeloid, Acute; Leukocytes; Male; Mediastinal Neoplasms; Muramidase; Phagocytosis; Rosette Formation

Serum beta 2 microglobulin levels, measured by radioimmunoassay (Phadebas test), were found increased in acute myeloid leukemias at diagnosis. Serum beta 2 microglobulin levels were significantly higher in patients with monocytic leukemias (13 patients, M4-M5 FAB classification) than in those with other cytological types (18 patients). Beta 2 microglobulin levels at diagnosis were correlated with serum lysozyme levels, but they were not correlated with blood blast counts, serum LDH and ferritin levels. 195 serum beta 2 microglobulin measurements were made serially in 30 patients with acute myeloid leukemias in first remission. Compared to values at diagnosis, beta 2 microglobulin levels in remission were significantly decreased. Out of 30 patients in remission 12 had increased serum beta 2 microglobulin levels (greater than 3 mg/l). Serial measurements were not predictive for relapses.

Topics: Adolescent; Adult; beta 2-Microglobulin; Creatinine; Female; Humans; Kidney; Leukemia, Myeloid, Acute; Male; Muramidase; Radioimmunoassay

Plasma and intracellular levels of lactate dehydrogenase (LDH), phosphohexose isomerase (PHI) and lysozyme activities were investigated in 20 patients with acute myelocytic leukemia (AML), 18 patients with acute lymphatic leukemia (ALL) and 10 patients with chronic myelocytic leukemia in blast transformation (CML/BT). Though the plasma levels of LDH and PHI in all patients with acute leukemia were elevated as compared to control persons there was no distinctive pattern which could be of use in the classification of acute leukemia. On the other hand the intracellular levels of these enzymes could be of value in classifying acute leukemia. The leukemic lymphoblasts were characterized by low levels of PHI and lysozyme as compared to leukemic myeloblasts or to normal lymphocytes (p less than 0.01). The LDH/PHI ratio is also significantly higher in leukemic lymphoblasts than in leukemic myeloblasts or in normal lymphocytes (p always less than 0.01). These characteristics might also be made use of in identifying the blasts of CML/BT als "lymphoid" or "myeloid" in corresponding cases.

Topics: Acute Disease; Adolescent; Adult; Aged; Child; Female; Glucose-6-Phosphate Isomerase; Humans; L-Lactate Dehydrogenase; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase; Neoplasm Proteins; Neoplastic Stem Cells; Stem Cells

A series of fluorescent probes was used to analyze membrane lipid dynamics in promyelocytic leukemic cells sensitive (HL-60) or resistant (R-55) to phorbol diester induction of cell differentiation. When examined with the probe 1,6-diphenyl-1,3,5-hexatriene, which can penetrate the plasma membrane and intercalate in the lipids of both leaflets of the plasma membrane, as well as in organellar membranes, R-55 cells were found to have higher fluorescence anisotropy values, indicative of decreased lipid fluidity, as compared to HL-60 cells. In contrast, when HL-60 and R-55 cells were compared using a series of membrane-impermeant fluorophores (stachyose derivatives of anthroyloxystearate and pyrenebutyryl hydrazide) that incorporate only into the outer hemileaflet of the plasma membrane, no difference was observed in membrane lipid fluidity. Exposure to 12-O-tetradecanoylphorbol-13-acetate (10 ng/ml) for 24 hr decreased the fluorescence anisotropy of 1,6-diphenyl-1,3,5-hexatriene in both HL-60 and R-55 cells, whereas by 48 hr only the HL-60 cells displayed the reduction. No effect on the fluorescence anisotropy of 1-(4'-trimethylammonium phenyl)-6-phenyl-1,3,5-hexatriene, which is believed to localize in the plasma membrane, was observed in R-55 cells exposed to 12-O-tetradecanoylphorbol-13-acetate (10 or 100 ng/ml), whereas HL-60 cells treated with 12-O-tetradecanoylphorbol-13-acetate (10 ng/ml) showed a marked reduction in the fluorescence anisotropy. These observations suggest that the ability of HL-60 cells to respond to 12-O-tetradecanoylphorbol-13-acetate may be affected by the physical state of the plasma membrane lipids and that the resistant phenotype is associated with decreased fluidity of either the inner leaflet of the plasma membrane and/or of the cytosolic organellar membranes.

Topics: Cell Differentiation; Cell Division; Cell Line; Cell Membrane; Drug Resistance; Fluorescence Polarization; Genetic Variation; Humans; Leukemia, Myeloid, Acute; Membrane Fluidity; Membrane Lipids; Muramidase; Phorbols; Tetradecanoylphorbol Acetate

Various human and mouse myeloid leukemia cell lines can differentiate to mature myeloid or monocytoid cells in response to different agents. The myeloblastic leukemia of the RFM/Un mouse (the RF.AML line) was studied here to determine its ability to differentiate after in vitro and in vivo treatment. The RF.AML cells were passed in vivo by i.v. or i.p. injection of freshly harvested leukemic spleen cells or in vitro-passaged leukemia cells. The cells proliferated in the spleen and peritoneal cavity. The RF.AML cells had the appearance of myeloblasts or myelomonoblasts on Wright's stain, had slight positivity for peroxidase, and lacked staining for nonspecific esterase. The cells grew in suspension in vitro with a doubling time of 48 hr. Various phorbol diester tumor promotors inhibited proliferation and incorporation of thymidine into the RF.AML cells. Phorbol myristate acetate (10 to 100 nM) caused the cells to adhere to plastic, and enhanced the phagocytic ability of the cells for Candida albicans. The RF.AML cells had specific receptors for phorbol dibutyrate, binding 0.37 +/- 0.03 (S.E.) pmol of [3H]phorbol dibutyrate/10(6) cells after a 2-hr incubation at 4 degrees with 50 nM [3H]phorbol dibutyrate. Thirty-three to 300 nM dexamethasone caused 19 to 37% of the cells to become nonspecific esterase positive and enhanced their phagocytosis of C. albicans. Likewise, 0.5 or 1.0 microM 13-cis-retinoic acid, or 0.6 or 1.2% dimethyl sulfoxide enhanced the phagocytic ability of the RF.AML cells but had no effect on the adherence, proliferation, or nonspecific esterase activity. None of the treatments induced lysozyme activity in the cells or rendered the RF.AML cells able to produce H2O2 in response to phorbol myristate acetate treatment in vitro. In vivo treatment of mice with RF.AML present with phorbol myristate acetate or dexamethasone did not induce differentiation of the RF.AML cells or alter the survival of the animals. Thus, although the RF.AML cells differentiate in vitro in response to various agents, in vivo differentiation was not seen in this model.

Topics: Animals; Caenorhabditis elegans Proteins; Carrier Proteins; Cell Differentiation; Cell Line; Dexamethasone; Dimethyl Sulfoxide; DNA Replication; Female; Leukemia, Experimental; Leukemia, Myeloid, Acute; Mice; Mice, Inbred Strains; Muramidase; Phorbol Esters; Protein Kinase C; Receptors, Drug; Receptors, Immunologic; Tetradecanoylphorbol Acetate; Tretinoin

The bone marrow biopsy specimens of 35 patients with benign and malignant erythroid hyperplasias were examined for the presence of hemoglobin A, hemoglobin F, muramidase (lysozyme), and transferrin, using an indirect immunoperoxidase method (PAP) on Zenker's-fixed paraffin-embedded bone marrow biopsy specimens and particles. Five cases of each of the following entities were studied: erythroleukemia and erythremic myelosis, acute granulocytic leukemia with maturation (FAB M2), polycythemia rubra vera, myeloproliferative syndrome in childhood, megaloblastic anemia (B12 and folate deficiency), erythroid hyperplasia (regenerating bone marrow and hemolytic anemia), and Ph' chromosome positive chronic granulocytic leukemia. Hemoglobin A was present in both the early and late erythroid precursors in all conditions. Hemoglobin F was the predominant hemoglobin in early erythroblasts of pernicious anemia and in both early and late erythroid elements in erythroleukemia and erythremic myelosis. Small quantities of hemoglobin F were present in a few isolated clusters in other conditions. Staining for hemoglobin F may be useful in identifying immature erythroid precursors and in distinguishing some cases of dysplastic erythroid hyperplasia from neoplasia. Additionally, these findings suggest that the maturational switch in hemoglobin synthesis operates with distinct pathways under different conditions.

Topics: Bone Marrow; Bone Marrow Diseases; Fetal Hemoglobin; Hemoglobin A; Histocytochemistry; Humans; Hyperplasia; Immunoenzyme Techniques; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid, Acute; Muramidase; Transferrin

A 55-year-old woman was described who developed an acute myelomonocytic leukemia 4 years after remission of sarcoidosis. This association is of particular interest since pronounced T cell dysfunction appears in sarcoidosis. We traced serum angiotensin-converting enzyme and serum or urinary lysozyme levels of this patient.

Topics: Clinical Enzyme Tests; Female; Humans; Leukemia, Myeloid, Acute; Middle Aged; Muramidase; Peptidyl-Dipeptidase A; Sarcoidosis

Forty-two patients with acute myelogenous leukemia or one of its variants were studied at diagnosis to determine the incidence and cause(s) of hypokalemia. Forty-three percent of patients were hypokalemic, and an inappropriate renal loss of potassium was noted. This potassium wastage could not be explained by antibiotic-induced renal tubular dysfunction, lysozymuria, or alterations in renin-aldosterone secretion.

Topics: Aldosterone; Anti-Bacterial Agents; Female; Humans; Hypokalemia; Kidney Tubules; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase; Potassium; Renin; Sodium

Pre-treatment sera and urines from 17 patients with acute myelomonocytic leukemia (M-4 type) have been assayed for their lysozyme content. In addition periodical evaluations of the serum and urinary lysozyme levels have been performed during the clinical course of 10 patients. There was no correlation between initial lysozyme activity in the serum and response to chemotherapy, while periodical estimations of serum lysozyme activity, in the same patient, provide clinically significant prognostic information. Urinary lysozyme levels are closely related to serum lysozyme levels; therefore the urinary estimations of this enzyme activity provide no different prognostic evaluations than serum estimations.

Topics: Adult; Aged; Antineoplastic Agents; Clinical Enzyme Tests; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase; Prognosis

1,25-Dihydroxyvitamin D3 [1,25(OH)2D3] stimulates bone resorption in man and other vertebrates, in part, by increasing the number of osteoclasts, the principal resorbing cells of bone. Because osteoclasts are very likely derived from a member(s) of the mononuclear phagocyte family, we determined if 1,25(OH)2D3 promotes maturation of these cells by studying its effects on the human promyelocytic leukemia cell line HL-60. Of the vitamin D3 metabolites tested, only 1,25(OH)2D3, at 10(-10) to 10(-7) M, induces the differentiation of HL60 into mono- and multinucleated macrophage-like cells. Phenotypic change is evident within 24 hr and reaches a plateau between 72 and 96 hr of incubation. The changes are metabolite-specific and include (i) adherence to substrate, (ii) acquisition of the morphological features of mature monocytes, (iii) a 4- to 6-fold enhancement in lysozyme synthesis and secretion, (iv) increase in the fraction of alpha-naphthyl acetate esterase-positive cells from approximately 2% to 100% of the population, and (v) the acquisition of several monocyte-associated cell surface antigens. More importantly, treated HL-60 cells acquire the capacity to bind and degrade bone matrix, two of the essential, functional characteristics of osteoclasts and related bone-resorbing cells. These results, considered together with the reported action of 1,25(OH)2D3 on nontransformed mononuclear cells, are consistent with the view that vitamin D3 enhances bone resorption and osteoclastogenesis in vivo by promoting the differentiation of precursor cells.

Topics: Animals; Bone Resorption; Calcitriol; Cell Differentiation; Cell Line; Flow Cytometry; Kinetics; Leukemia, Myeloid, Acute; Monocytes; Muramidase; Osteoclasts

An analysis of the chromosomal karyotype of the human promyelocytic HL-60 leukemia cell line and of a number of its sublines that exhibit varying degrees of resistance to induction of differentiation by phorbol-12-myristate-13-acetate was conducted. The HL-60 cell line and the derived sublines contained two consistent marker chromosomes [9p- and t(10;13)], which suggested that they have a common and possibly clonal origin. HL-60 cells that are susceptible to phorbol-12-myristate-13-acetate-induced cell differentiation contained double minute chromatin bodies. The sublines with different degrees of resistance showed a corresponding sequential reduction of double minute chromatin bodies in metaphase cells. This loss of double minute chromatin bodies was not associated with an appearance of homogeneously staining chromosomal regions. Resistant and susceptible HL-60 cells differed also in a number of other chromosomal alterations, including gains or losses involving chromosomes 5, 8, 11, 13, 16, and 17. Thus, it is suggested that acquisition of resistance to phorbol-12-myristate-13-acetate-induced cell differentiation in the HL-60 cells may involve one or more of the above chromosomal changes.

Topics: Cell Differentiation; Cell Line; Chromatin; Chromosome Aberrations; Chromosome Banding; Chromosome Disorders; Drug Resistance; Humans; Karyotyping; Leukemia, Myeloid, Acute; Muramidase; Phorbols; Tetradecanoylphorbol Acetate

12-)-Tetradecanoylphorbol-13-acetate (TPA), the prototype polyfunctional diterpene ester tumor promoter of two-step carcinogenesis in mouse skin, induced differentiation of human promyelocytic leukemia cells (HL-60) in culture. Differentiation of HL-60 cells was characterized by increased phagocytosis, increased lysozyme activity (EC 3.2.1.17) in the growth medium, and changes in morphology to those characteristics of more mature cells resembling macrophages. Many of the cells treated with TPA became aggregated, attaching firmly to culture flasks. The average intracellular myeloperoxidase activity (EC 1.11.1.7) per cell decreased during induction of differentiation by TPA. It was also found that TPA enhanced, rather than inhibited, differentiation of HL-60 cells induced by DMSO. In addition to TPA, several polyfunctional diterpene esters of the tigliane, ingenane, and daphnane type have been tested for their ability to induce morphological and functional changes of HL-60 cells. The activities of the compounds to induce these changes correlated well with their activities as tumor promoters in two-step carcinogenesis in mouse skin. In particular, half the concentrations required for induction of adhesion of the cells to flasks were roughly correlated to the potency of these compounds as tumor promoters. Among the compounds tested, phorbol-12,13-didecanoate (PDD), ingenol-3-hexadecanoate, Pimelea factor P1 and Pimelea factor P2 were as active as TPA, while 4-O-methyl-TPA and 4 alpha-PDD were much less active. Phorbol and ingenol were totally inactive up to a concentrations 10,000-fold higher than that of TPA.

Topics: Cell Adhesion; Cell Line; Cells, Cultured; Dimethyl Sulfoxide; Diterpenes; Humans; Leukemia, Myeloid, Acute; Muramidase; Peroxidase; Phagocytosis; Phorbol Esters; Tetradecanoylphorbol Acetate

Topics: Blood Proteins; Cell Differentiation; Cell Line; Cell Separation; Culture Media; Cytoplasmic Granules; Granulocytes; Hematopoiesis; Humans; Leukemia, Myeloid, Acute; Muramidase; Neutrophils; Peroxidase

Topics: Acid Phosphatase; Adult; Cell Differentiation; DNA Nucleotidylexotransferase; Esterases; Granulocytes; Histocytochemistry; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Monocytes; Muramidase; Peroxidase

Retinoic acid and retinol induced functional and morphological differentiation of human promyelocytic leukemia cells (HL-60) into mature granulocytes, but did not induce functional or morphological differentiation of mouse myeloid leukemia cells (M1). Cellular retinoic acid-binding protein, but not retinol-binding protein, was detected on HL-60 cells. Neither binding protein could be detected on M1 cells. These results suggest that retinoic acid-binding protein may be necessary for induction by retinoids of functional and morphological differentiation of myeloid leukemia cells.

Topics: Animals; Carrier Proteins; Cell Transformation, Neoplastic; Cells, Cultured; Enzyme Induction; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mice; Muramidase; Neoplasm Proteins; Rats; Receptors, Retinoic Acid; Retinol-Binding Proteins; Tretinoin

Polyamine levels were evaluated in human HL-60 promyelocytic leukemia cells after treatment with inducers of terminal differentiation. Differentiation in these cells was determined by increases in the percentage of morphologically mature cells and in lysozyme activity. Treatment of the HL-60 cells with phorbol 12-myristate-13-acetate (PMA), phorbol 12,13-didecanoate or other inducers of terminal differentiation such as dimethylsulfoxide and retinoic acid resulted in increased levels of putrescine. However, no increase in putrescine could be detected after PMA treatment of a HL-60 cell variant that exhibited a decreased susceptibility to PMA-induced terminal differentiation. Similarly, no increase in putrescine was observed with two non-tumor-promoters (phorbol 12,13-diacetate and 4-O-methyl-PMA) or with anthralin, a non-phorbol tumor promoter. In addition to enhancing putrescine levels, PMA also increased the amount of spermidine and decreased the amount of spermine. The increase in putrescine and spermidine preceded the expression of the various differentiation markers. Unlike the changes observed in the polyamine levels after PMA treatment, the activities of ornithine and S-adenosylmethionine decarboxylases, which are polyamine biosynthetic enzymes, did not significantly change. alpha-Methylornithine and alpha-difluoromethylornithine and methylglyoxal bis(guanylhydrazone), which are inhibitors of the polyamine biosynthetic enzymes, did not affect differentiation in control or PMA-treated cells. Because of these observations, we suggest that the change in polyamine levels involve biochemical pathways other than the known biosynthetic ones. By-products of these pathways may perhaps be the controlling factors involved in the induction of terminal differentiation in the HL-60 and other cell types as well.

Topics: Cell Differentiation; Cell Line; Humans; Kinetics; Leukemia, Myeloid, Acute; Muramidase; Phorbol Esters; Phorbols; Polyamines; Putrescine; Spermidine; Spermine; Tetradecanoylphorbol Acetate

Topics: Acid Phosphatase; Cell Differentiation; Cell Line; Dimethyl Sulfoxide; Fibrinolysis; Humans; Leukemia, Myeloid, Acute; Muramidase; Tretinoin

Topics: Child; Child, Preschool; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Muramidase

Topics: Humans; Leukemia; Leukemia, Hairy Cell; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Muramidase

Topics: Bone Marrow; Cells, Cultured; Clone Cells; Diagnosis, Differential; Etoposide; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Muramidase; Prognosis; Transcobalamins

Topics: Humans; Hypokalemia; Leukemia, Myeloid, Acute; Muramidase; Sarcoidosis; Tuberculosis

We have systematically investigated a variety of fixation and plastic embedding procedures and arrived at a method that allows processing of approximately 2-micron sections of bone marrow biopsies for examination by light microscopy. More importantly, this method permits the use of enzyme histochemical and immunohistochemical procedures that are rapidly becoming mandatory in the diagnosis of hematologic malignancies. Over 200 full-length bone marrow biopsy specimens were fixed in a mixture of paraformaldehyde, glutaraldehyde, and acrolein, dehydrated in acetone, and embedded in a mixture of methyl and glycolmethacrylate. All procedures were carried out at 4 degrees C. Decalcification was unnecessary. Sections 2-micron thick were cut and incubated for peroxidase, naphthol AS-D chloroacetate esterase, alpha-naphthyl butyrate esterase, acid phosphatase (with and without tartrate), or alkaline phosphatase and then examined by light microscopy. Specimens could be prepared for examination within 48 hr. This approach, which provides definitive markers for various hematopoietic cell lines in intact tissues, is invaluable when aspirated material is unavailable. It is also useful in the analysis of focal lesions of bone marrow due to inflammation or neoplasia and shows potential as an investigative tool. For example, we have discovered that early myelofibrosis is accompanied by a marked increase in the number of alkaline-phosphatase-positive reticulum cells.

Topics: Bone Marrow; Carboxylic Ester Hydrolases; Fixatives; Histocytochemistry; Humans; Immunoenzyme Techniques; Incubators; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Macrophages; Monocytes; Muramidase; Phagocytes

Topics: Animals; Cell Differentiation; Cell Division; Cell Line; Interferons; L Cells; Leukemia, Experimental; Leukemia, Myeloid, Acute; Macrophages; Mice; Muramidase; Phagocytosis; Poly I-C; Receptors, Fc

Phorbol esters, including 12-O-tetradecanoylphorbol 13-acetate (TPA), induce terminal macrophagelike differentiation of cells from human acute myelogenous leukemia lines. We report that myelogenous leukemia cells obtained from patients undergo macrophagelike differentiation after exposure to TPA. The myeloid leukemic cell cultured with TPA became adherent to charged surfaces with long filamentous pseudopodia; developed positive staining for alpha-napthyl acetate esterase, increased lysozyme secretion, reduced nitroblue tetrazolium, and acquired the ability to phagocytose candida. Cells from patients with lymphocytic leukemia did not become macrophagelike when cultured with TPA.

Topics: Cell Adhesion; Cell Differentiation; Histocytochemistry; Humans; Leukemia, Myeloid, Acute; Macrophages; Muramidase; Naphthol AS D Esterase; Nitroblue Tetrazolium; Peroxidase; Phagocytosis; Phorbols; Sodium Fluoride; Tetradecanoylphorbol Acetate

Topics: Enzyme Activation; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocytes; 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

The diagnostic and prognostic value of the assay of lysozyme in serum and urine was appreciated in 184 cases of acute leukemia. The levels were decreased in the lymphoblastic, mainly of the non B-non T type, and undifferenciated varieties, markedly raised in the monoblastic and myelo-monocytic varieties, while in the myeloblastic ones they were found normal, decreased or slightly increased, and, on the average, significantly higher in the well differenciated than in the poorly differenciated types. For a given cytological type, the level of lysozyme is not correlated with the frequency of the induction of complete remission. However, in the acute myeloblastic leukemia, a significantly higher frequency of infection during or after the induction treatment was observed in the cases presenting initially without a raised serum lysozyme level.

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Prognosis

Serum lysozyme activity was measured in samples from adult patients with acute leukemia, malignant tumors, and in normal adults. Twenty-eight adult patients with acute myelogenous leukemia (AML) had significantly elevated levels of lysozyme at diagnosis, and none of the adults fell within the normal range. Thirty-two patients with AML in complete remission had lysozyme levels comparable to normal adults, whereas patients with AML in relapse (eight cases) also had abnormally high levels of lysozyme activity. Ten patients with AML in remission and off therapy also had normal lysozyme levels. Three patients with acute lymphatic leukemia had normal lysozyme levels, while one child with monomyelocytic leukemia had substantially elevated lysozyme levels before treatment. It seems that in patients in remission and with normal blood values, the serum lysozyme activity is valuable for monitoring the remission.

Topics: Adult; Antineoplastic Agents; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Lymphoma; Lymphoma, Non-Hodgkin; Muramidase; Prognosis; Remission, Spontaneous

In a consecutive series of 22 patients with acute leukemia, the total body potassium was studied in 18 patients on 39 occasions during relapse and remission. Total body water was also determined. A control group consisting of 88 age-matched healthy volunteers was also studied. The patients had a significantly lower mean potassium concentration, per kg body weight, per kg lean body mass and per kg water, than the controls (p less than 0.001). Individually, 11 out of the 18 patients had at least one value below the lower 95% confidence limit. Hypokalemia was frequent both in the patients with low (7/11) and normal (3/6) potassium per kg lean body mass. Five of 13 investigated patients showed laboratory indications of secondary hyperaldosteronism, which might be partly responsible for the hypokalemia. Increased serum or urine levels of lysozyme were found in 62% of the patients.

Topics: Adult; Aged; Aldosterone; Antineoplastic Agents; Electrolytes; Female; Humans; Hypokalemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase; Potassium; Renin

Topics: Adult; Humans; Leukemia, Myeloid, Acute; Muramidase

Mouse myeloid leukemic cells which differ in their competence to be induced to differentiate by the normal macrophage- and granulocyte-inducing protein MGI have been used to study the relationship between type C RNA virus production and myeloid cell differentiation. Clones which can be induced by MGI to form Fc and C3 rosettes, to synthesize and secrete lysozyme and to differentiate to mature macrophages and granulocytes (MGI+D+) were induced by MGI to produce higher amounts of type C virus. Clones (MGI+D-) that were less inducible by MGI for Fc and C3 rosettes and lysozyme and were not induced to from mature cells were also less inducible higher virus production. In both types of clones, the increased virus production induced by MGI preceded the induction of rosettes and lysozyme. Clones that were not induced by MGI for rosettes or lysozyme (MGI-D-) showed little or no enhancement of virus production. MGI did not affect virus production in erythroleukemic cells, and erythropoietin did not affect virus production in the myeloid leukemic cells. Dexamethasone, lipopolysaccharide, dimethylsulfoxide and low concentrations of actinomycin D can induce some differentiation-associated properties in some of the clones. With these compounds, there was also a direct relationship between the enhancement of virus production and induction of differentiation-associated properties. Virus released from the three types of clones before or after treatment with MGI or dexamethasone was identified as N-tropic. The enhancement of virus production, as measured by reverse transcriptase activity, was accompanied by an increase in the amount of the viral protein p30, and interferon, which idd not inhibit the induction of differentiation in the myeloid leukemic cells, also did not prevent the increase in the amount of p30. After the early enhancement of virus production associated with the induction of differentiation, a shut-off of virus production occurred in the mature cells induced by MGI in MGI+D+ clones, whereas clones that did not differentiate to mature cells continued to produce virus. The results indicate that enhancement of virus production appears to be an early step in the induction of differentiation. Once induction has occurred, the lack of virus production in the mature cells suggest that a subsequent shut-off of virus production may be required for the completion of differentiation to mature cells. This relationship between cell differentiation and virus production

Topics: Animals; Cell Differentiation; Cell Line; Colony-Stimulating Factors; Dexamethasone; Interferons; Leukemia, Experimental; Leukemia, Myeloid, Acute; Muramidase; Retroviridae; RNA-Directed DNA Polymerase; Rosette Formation; Viral Proteins; Virus Replication

Topics: Alkaline Phosphatase; Animals; Antigens, Viral; Bone Marrow; Butyrates; Cell Line; Cells, Cultured; Dose-Response Relationship, Drug; Esterases; Herpesvirus 4, Human; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Rats

Normal myeloid and MGI(+)D(+) clones of myeloid leukemic cells can be induced for Fc and complement component 3 rosettes, lysozme, and mature macrophages and granulocytes by a protein with macrophage- and granulocyte-inducing (MGI) activity, whereas MGI(+)D(-) clones can be induced by this protein for rosettes and lysozme but not mature cells. Lipopolysaccharides (LPS) from different bacteria induced the appearance of rosettes, lysozyme, and macrophages in some MGI(+)D(+) clones but did not induce any of these changes in MGI(+)D(-) clones. Lipid A gave the same results as LPS. Incubation of MGI(+)D(+) cells with LPS also induced an MGI activity detectable in the culture medium. This activity behaved like MGI in inducing (i) rosettes, lysozyme, and mature cells in MGI(+)D(+) leukemic cells including a clone resistant to LPS, (ii) rosettes and lysozyme in MGI(+)D(-) leukemic cells, and (iii) differentiation of normal myeloid cells to mature macrophages and granulocytes. This activity was induced in MGI(+)D(+) cells by LPS before the induction of rosettes or lysozyme. The results indicate that the lipid A portion of LPS indirectly induces differentiation of MGI(+)D(+) myeloid leukemic cells by inducing MGI protein. It is suggested that induction of specific regulatory proteins may be a more general mechanism for the induction of differentiation by surface-acting compounds.

Topics: Animals; Binding Sites; Cell Differentiation; Complement C3; Growth Substances; Immunoglobulin Fc Fragments; Leukemia, Experimental; Leukemia, Myeloid, Acute; Lipid A; Lipopolysaccharides; Macrophages; Muramidase; Species Specificity

Serum lysozyme activity was measured in samples from children with acute leukemia, malignant tumours, and in normal children. All children with acute lymphatic leukemia (ALL) had significantly reduced levels of lysozyme at diagnosis, and none of the children fell within the normal range. Children with ALL in complete remission had lysozyme levels comparable to normal chidren, while children with ALL in relapse also had pathological low levels. Children with ALL in remission and off therapy also had normal levels of lysozyme. Children with acute myelogenous leukemia had normal lysozyme levels, while children with monomyelocytic leukemia had substantially elevated lysozyme levels before treatment. Determination of serum lysozyme activity in children with acute leukemia is of value both for diagnosis and for evaluating the effect of therapy.

Topics: Acute Disease; Child; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Remission, Spontaneous

Topics: Hematologic Diseases; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma; Muramidase; Myeloproliferative Disorders

Topics: Acid Phosphatase; Histocytochemistry; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Muramidase; Naphthol AS D Esterase; Peroxidases

The authors report the data on immunoglobulins G, A, M content and their relationship with other factors of natural immunity in 55 patients with acute myeloblastic leukemia and in 43 patients with chronic lymphatic leukemia. The results have evidenced the impaired synthesis of immunoglobulins in acute in acute leukemia and the reduction of IgA and IgM already in the initial stage of chronic lymphatic leukemia. A correlation between mean values of immunoglobulins content and other factors of immunological resistance allowed a statement to be made that in the absence of impaired immunoglobulins synthesis there is a distinct coincidence of immunoglobulin content curves and titres of agglutinating and bacteriolytic antibodies.

Topics: Agglutination Tests; Antibodies, Bacterial; Bacteriolysis; Humans; Immunity, Innate; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Muramidase; Phagocytosis; Salmonella typhimurium; Staphylococcus

The amount of lysozyme in the leukocytes of 47 patients with different forms of leukaemia and 6 healthy persons was investigated. The lysozyme determination was carried out in the lysate of isolated leukocytes obtained after freezing and thawing it seven times. The results expressed in microgram per 10(6) cells were compared with the simultaneously determined lysozyme concentration of serum and urine. A substantial reduction of the lysozyme amount as compared with the normal value (3.1 microgram/10(6) cells) was determined in the leukocytes of patients suffering from chronic lymphatic leukaemia, acute lymphatic leukaemia and the blastic crisis of chronic myeloid leukaemia. Different amounts of lysozyme ranging from extremely low ones to strongly elevated ones were found in leukocytes taken from patients with acute myeloblastic and chronic monocytic leukaemia. In many cases there was a lack of correlation between the lysozyme content of leukocytes on the one hand and that of serum and urine on the other hand. Possible causes underlying this lack of correlation are discussed.

Topics: Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Muramidase

The purified chromatin of leukocyte nuclei from two patients, one with chronic granulocytic and another with acute myelomonocytic leukemia, has been investigated for lysozyme activity. The chromatin contained 4.8% resp. 4% of the total amount of lysozyme found in the leukocytes. The function of lysozyme in the nucleus remains unclear.

Topics: Blood Proteins; Cell Nucleus; Chromatin; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Muramidase

Topics: Granulocytes; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Monocytes; Muramidase

A simple cytochemical and cytobacterial method for the simultaneous demonstration of peroxidase and lysozyme (muramidase) activities in individual cells was devised. In characterization of myeloid and monocyte series, the combination of these myeloid- and monocyte-specific enzymes not only was more informative than a single enzyme but made it easier to differentiate acute myelomonocytic leukemia, with higher lysozyme activity, from acute myeloid leukemia, with higher peroxidase activity. Acute lymphocytic leukemia had no lysozyme or peroxidase activity.

Topics: Bone Marrow; Bone Marrow Cells; Histocytochemistry; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Peroxidases

Serum lysozyme (muramidase) estimation is a simple, convenient and useful laboratory investigation. A review of the literature shows that lysozyme has been implicated as an aetiological factor in various disorders, and credited with being a prognostic indicator in acute myeloid leukaemia, but these promises have not been fulfilled. This low molecular weight protein is found in the urine of some patients with renal tubular disorders, but some workers have emphasized its importance as a causal agent in hypokalaemia of acute myeloid leukaemia. Research should be concentrated on muramidase as an expression of cell functions rather than as an aetiological factor. Hypokalaemia in acute myeloid leukaemia may be caused by an unidentified substance of molecular weight similar to that of lysozyme.

Topics: Animals; Humans; Hypokalemia; Kidney Diseases; Leukemia, Myeloid, Acute; Muramidase; Prognosis

In sera of patients with acute leucosis the authors have determined antibodies to alpha-toxin, streptolysin-O, the complement, lysosyme. B-lysins and C-reactive protein. It was found that the indices of immune reactivity in patients with acute leucosis are dependent on a morphological variant of the disease, the duration of the conducted therapy and presence of complications. The most high immunity indices in patients with acute leucosis were observed in a primary active stage of the disease and during the period of remission. Considerable reduction of the immunity was noted in the terminal stage of the disease.

Topics: Adult; Aged; Amino Acid Isomerases; Antistreptolysin; Antitoxins; C-Reactive Protein; Complement System Proteins; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase

Topics: Child; Child, Preschool; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Male; Muramidase

Serum lysozyme activity has been determined in patients suffering from myeloproliferative diseases, chronic myelogenous leukaemia (CML), acute myelogenous leukaemia (AML), chronic lymphatic leukaemia (CLL) and pancytopenia (P). Lysozyme activity was tested in undiluted and tenfold diluted sera. Increased lysozyme activity was found in patients with CML and CLI, whereas there was no change in patients with AML and P. Dilution of sera enhanced lysozyme activity. These data may indicate the presence of inhibitor in the sera tested. The diagnostic significance of the presented findings is discussed.

Topics: Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Myeloproliferative Disorders; Pancytopenia

Leukemic cells from nine cases of acute monocytic leukemia (AMoL) were characterized by multiple differentiation markers. Cells in most cases were phagocytic, carried an Fc receptor, and stained positively for alpha-naphthyl acetate esterase but negatively for naphthol AS-D chloroacetate esterase. However, subtle differences in marker expression were observed which suggested different degrees of leukemic cellular maturation or activation. Cell marker analysis proved to be a useful adjunct to conventional morphology in confirming the diagnosis and the recognition of the neoplastic cells in AMoL, and may ultimately provide insight into the functional state of these cells.

Topics: Esterases; Female; Fluorescent Antibody Technique; Humans; Immunologic Techniques; Leukemia, Myeloid, Acute; Male; Middle Aged; Monocytes; Muramidase; Phagocytosis; Receptors, Antigen, B-Cell

Samples from 49 cases of myeloproliferative diseases were tested by an immunocytochemical technique for leucocyte lysozyme and lactoferrin. The presence of these constituents in myeloid precursors from cases of acute and chronic myeloid leukaemia reflected the degree of cellular maturation, lysozyme appearing (as it does in normal myeloid cells) at the stage of primary granule production (in promyelocytes), while lactoferrin wad detectable only in more mature, secondary granule-containing myeloid cells. Auer rods stained positively for lysozyme, in keeping with their relationship to primary granules. Monocytes from five cases of leukaemia showing predominantly monocytic differentiation were indistinguishable from normal monocytes in their staining reactions for lysozyme despite the presence of raised serum and urinary lysozyme levels. In four cases of acute myeloid leukaemia circulating polymorphs deficient in lactoferrin were detected: in one of these cases a similar percentage of polymorphs was lysozyme negative.

Topics: Humans; Immunoenzyme Techniques; Intracellular Fluid; Lactoferrin; Lactoglobulins; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocytes; Monocytes; Muramidase; Myeloproliferative Disorders; Neutrophils

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

Pre-treatment sera from 88 adult patients with acute myelogenous leukaemia have been assayed for their lysozyme content. All 19 patients who presented with a serum-lysozyme level below 15 mug/ml failed to acheive haematological remission from intensive chemotherapy. Serum-lysozyme levels above 85 mug/ml were found in 10 patients, all of whom went into remission. Remissions in this group were, however, shortlived. Of the 59 patients with lysozyme levels between 15 and 85 mug/ml, 39 achieved haematological remission and 12 survived longer than 60 weeks. These findings suggest that estimation of serum-lysozyme may help to identify those patients who are unlikely to respond to the intensive-chemotherapy protocols currently advocated and who could therefore be spared exposure to them.

Topics: Adult; Antineoplastic Agents; Humans; Leukemia, Myeloid, Acute; Muramidase; Prognosis; Remission, Spontaneous

Topics: Humans; Leukemia, Myeloid, Acute; Muramidase; Prognosis; Remission, Spontaneous

Topics: Adult; Clinical Enzyme Tests; Hematologic Diseases; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Polycythemia Vera; Primary Myelofibrosis; Urine

The production of colony-stimulating factor (CSF) by the peripheral blood cells of untreated patients with acute myeloid leukemia (AML) was measured in the agar culture system using normal human bone marrow as the source of colony-forming units (CFUc). CSF production was found to be variable and was related to the morphologic subtype of AML--cells from patients with monocytic leukemia produced normal or large quantities of CSF, while (with one exception) those from patients with myeloblastic leukemia produced little or no CSF. There was a general relationship between CSF production and serum lysozyme levels. Attempts to demonstrate a consistent inhibitory effect exerted by leukemic peripheral blood cells on normal leukopoiesis in vitro were negative. Results instead suggested that the addition to the feeder layer of cells from patients with monocytic leukemia could raise CSF levels above those obtained with normal peripheral blood leukocytes alone, possibly by recruiting additional CFUc from normal marrow.

Topics: Adult; Aged; Cells, Cultured; Colony-Stimulating Factors; Culture Techniques; Female; Glycoproteins; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Middle Aged; Muramidase

The interaction of N-acetyl-chitotriose ((GlcNAc)3) with human lysozyme [EC 3.2.1.17] was studied at various pH values by measuring changes in the circular dichroic (CD) band at 294 or 255 nm and the data were compared with the results for hen and turkey lysozymes reported previously (Kuramitsu et al. (1974) J. Biochem.76, 671-683; Kuramitsu et al. (1975) J. Biochem. 77, 291-301). The pH dependence of the binding constant of (GlcNAc)3 to human lysozyme was different from those for hen and turkey lysozymes. The catalytic carboxyls of human lysozyme, Asp 52 and Glu 35, were not perturbed on binding of (GlcNAc)3. This is consistent with the previous findings that the macroscopic pK values of Asp 52 and Glu 35 of human lysozyme are 3.4 and 6.8 at 0.1 ionic strength and 25 degrees and were unchanged on complexing with (GlcNAc)3. An ionizable group with pK 4.5, which participates in the binding of (GlcNAc)3 to hen lysozyme and was assigned as Asp 101, did not participate in the binding of the saccharide to human lysozyme. Between pH 9 and 11, the binding constants of (GlcNAc)3 to hen lysozyme remained unchanged, whereas perturbation of an ionizable group with pK 10.5 to 10.0 was observed for human lysozyme. This group may be Tyr 62 in the active-site cleft. The binding constants of (GlcNAc)3 to human lysozyme molecules having different microscopic protonation forms, with respect to the catalytic carboxyls, were estimated using the binding constants obtained in the present experiments and the microscopic ionization constants of the catalytic carboxyls obtained previously. All four species of human lysozyme had similar binding constants to (GlcNAc)3. This result is different from those for hen and turkey lysozymes.

Topics: Acetylglucosamine; Animals; Binding Sites; Chickens; Circular Dichroism; Female; Humans; Hydrogen-Ion Concentration; Kinetics; Leukemia, Myeloid, Acute; Mathematics; Muramidase; Oligosaccharides; Protein Binding; Protein Conformation; Species Specificity; Turkeys

Topics: Aldosterone; Humans; Hydrocortisone; Hydrogen-Ion Concentration; Hypokalemia; Kidney; Leukemia, Myeloid, Acute; Muramidase; Potassium; Proteinuria

Five cases of acute promyelocytic leukaemia (A.P.L.) are investigated for peroxidase, PAS, toluidine blue, astra blue, alpha-naphthyl esterase, double esterase incubation (naphthol-AS plus naphthol-AS-D chloroesterase), and cellular lysozyme activity. These cytochemical investigations may contribute further characterization of the morphologic type.

Topics: Adult; Bone Marrow Examination; Clinical Enzyme Tests; Esterases; Female; Humans; Leukemia, Myeloid, Acute; Muramidase; Peroxidases; Staining and Labeling

A transplantable myelogenous leukemia of an inbred Wistar/Furth rat has been established in tissue culture and cloned. The resulting transplantable leukemia line demonstrates in vitro doubling time of 20 hr, colony-forming efficiency of 5% in liquid and methylcellulos-containing medium, and a saturation density of 3.0 x 106 cells/sq cm in liquid medium. Following intraperitoneal inoculation, newborn rats developed solid tumors, ascities, and leukemia with ld50 of5 x 103 cells and mean latency of 60 days. The tumor cell morphology was consistent with that of acute myelogenous leukemia. Histochemical staining for myeloid enzymes revealed no evidence of myeloperoxidase, esterase, or leukocyte alkaline phosphatase; however, fluorescent antibody staining for lysozyme was markedly positive. Serum, urine, and ascitic fluid from rats with transplanted leukemia also contained elevated levels of lysozyme. There was no detectable type-CRNA virus production by this cell line after as long as 100 days in vitro. This inbred rat myelogenous leukemia should provide a useful model for studies of chemotherapy and immunoltherapy of human acute myelogenous leukemia.

Topics: Animals; Animals, Newborn; Ascitic Fluid; Cell Division; Cell Line; Culture Media; Culture Techniques; Disease Models, Animal; DNA; Female; Fluorescent Antibody Technique; Histocytochemistry; Leukemia, Experimental; Leukemia, Myeloid, Acute; Leukocytes; Muramidase; Pregnancy; Rats; Retroviridae; RNA-Directed DNA Polymerase; Staining and Labeling; Strontium Radioisotopes; Urine

The electrophoretic mobility of serum lysozyme in 2 patients with raised enzyme levels was identical to that of gamma-globulins. Similar mobility was observed after incubation of lysozyme and normal serum. Incubation with one hypogammaglobulinemic serum showed that lysozyme could also acquire alpha2 mobility.

Topics: Agammaglobulinemia; Alpha-Globulins; Electrophoresis, Cellulose Acetate; gamma-Globulins; Humans; Leukemia, Myeloid, Acute; Leukocytosis; Muramidase

Topics: Alkaline Phosphatase; Bone Marrow; Bone Marrow Cells; Cell Differentiation; Clone Cells; Esterases; Leukemia, Myeloid, Acute; Muramidase; Peroxidases; Retroviridae

Topics: Animals; Disease Models, Animal; Humans; Hypokalemia; Leukemia, Myeloid, Acute; Muramidase; Rats

Pretreatment serum lysozyme activity was high in 2 children with myelomonocytic leukemia, 800 and 1 000 mug/ml, normal in all 10 cases of acute lyelocytic leukemia and subnormal in 21 of 34 cases of acute lymphocytic leukemia. Normal values were found in all but one case of acute lymphocytic leukemia during complete remission including 8 cases after all therapy had been discontinued. All 8 are still in complete remission. Low serum lysozyme activity was found in 5 patients with acute lymphocytic leukemia in complete relapse, this could possibly be helpful in the diagnosis of early relapse. Activity was subnormal in 5 of 17 children with malignant tumours, and in 3 of 65 cases of various benign hematological disorders.

Topics: Child; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Muramidase

Topics: Adult; Aged; Blood Cell Count; Bone Marrow; Bone Marrow Cells; Cell Division; Clone Cells; Cytarabine; DNA; Doxorubicin; Female; Glycoproteins; Hematopoiesis; Humans; Leukemia, Myeloid, Acute; Lymphoma; Male; Mitosis; Muramidase; Thioguanine; Thymidine; Tritium

Topics: Adult; Cell Separation; Hematopoietic Stem Cells; Humans; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Methotrexate; Muramidase; Neutrophils; Recurrence

Topics: Adult; Animals; Cattle; Centrifugation; Contraceptives, Oral; Erythrocytes; Female; Ferritins; Humans; Iron; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Male; Muramidase; Radioimmunoassay; Serum Albumin, Bovine; Sex Factors; Sodium Chloride; Ultrasonics

Two patients with acute myeloid leukaemia developed hypouricaemia during the period of their illness. Renal clearance studies showed that the hypouricaemia was associated with an increased urate clearance, renal aminoaciduria, and an episodic increase in phosphate clearance. These findings together with an inadequate suppression of urinary urate exceretion after the administration of pyrazinamide suggest proximal tubular dysfunction affecting reabsorption of a wide variety of substances. Ten more patients with acute leukaemia were studied and the results indicate that this lesion develops in a large proportion of patients with acute myeloid leukaemia.

Topics: Amino Acids; Calcium; Creatinine; Cytarabine; Daunorubicin; Female; Humans; Hydrogen-Ion Concentration; Kidney Diseases; Kidney Tubules, Proximal; Leukemia, Myeloid, Acute; Middle Aged; Muramidase; Phosphates; Phosphorus; Pyrazinamide; Uric Acid

Topics: Administration, Oral; Adolescent; Adult; Age Factors; Aged; Anemia; Child; Cytarabine; DNA, Neoplasm; Female; Humans; Injections, Intravenous; Leukemia, Myeloid, Acute; Leukocytes; Male; Middle Aged; Muramidase; Nausea; Remission, Spontaneous; Sex Factors; Thioguanine; Thrombocytopenia; Time Factors; Vomiting

Topics: Anemia, Sideroblastic; Bone Marrow Examination; Cytarabine; Female; Humans; Immunodiffusion; Immunoelectrophoresis; Immunoglobulins; Iron; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Melphalan; Mercaptopurine; Middle Aged; Multiple Myeloma; Muramidase; Precancerous Conditions; Prednisone; Staining and Labeling; Vincristine

Topics: Acid Phosphatase; Esterases; Exudates and Transudates; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Monocytes; Muramidase; Skin Window Technique

The cytochemical methods for lysozyme and nitroblue-tetrazolium reduction have been used to study the blast cells of acute myeloid leukaemia. Both proved useful in characterizing the cases with predominant monocytic differentiation. THE DEMONSTRATION OF LYSOZYME ACTIVITY HELPED TO DEFINE TWO MAIN GROUPS: (a) with predominantly lysozyme-negative cells (myeloblastic-promyelocytic), and (b) with considerable numbers of positive cells (monoblastic-monocytic). In addition this test was also of value in the differentiation of other leukaemic disorders. Reduction of nitroblue-tetrazolium was also a feature of monocytic differentiation. The combination of these two methods with those for myeloperoxidase and non-specific esterase activity contributes to the cytological characterization of acute myeloid leukaemia.

Topics: Cell Differentiation; Esterases; Histocytochemistry; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Muramidase; Oxidation-Reduction; Peroxidases; Tetrazolium Salts

Topics: Adult; Female; Hematologic Diseases; Humans; L-Lactate Dehydrogenase; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Lymphocyte Activation; Male; Muramidase; Remission, Spontaneous; Uric Acid

In human leukemic myeloblasts, the granule enzymes beta-glucuronidase, myeloperoxidase and acid phosphatase were associated with light particles of varying densities that were separable from each other by means of zonal density gradient centrifugation. In more mature granulocytic cells of chronic myelogenous leukemia the three enzymes merged within a single group of denser particles; such particles were absent in myeloblasts. Myeloblast particles had two to three times higher activity of beta-glucuronidase and acid phosphatase, but only one-tenth of the myeloperoxidase activity. Some of the cationic proteins and lysozyme were not found in leukemic myeloblasts but were present in particles of chronic myelogenous leukemia; alkaline phosphatase was absent from both types of leukemic cells.

Topics: Acid Phosphatase; Alkaline Phosphatase; Centrifugation, Density Gradient; Cytoplasmic Granules; Electrophoresis, Paper; Glucuronidase; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Muramidase; Peroxidases; Subcellular Fractions

Topics: Adult; Cytarabine; Daunorubicin; Diagnosis, Differential; Drug Evaluation; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Prognosis; Remission, Spontaneous; Thymidine; Tritium

Topics: Autopsy; Bone Marrow; Bone Marrow Cells; Chlorambucil; Humans; Immunoglobulins; Karyotyping; Leukemia, Myeloid, Acute; Lymph Nodes; Lymphoma, Non-Hodgkin; Male; Middle Aged; Muramidase; Neoplasms, Multiple Primary; Prednisone

Topics: Acute Kidney Injury; Female; Humans; Hypokalemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Middle Aged; Muramidase

Topics: Humans; Leukemia, Myeloid, Acute; Monocytes; Muramidase; Phagocytosis; Staining and Labeling; Tetrazolium Salts

Topics: Adolescent; Adult; Aged; Diagnosis, Differential; Esterases; Histocytochemistry; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocytes; Lymphocytes; Middle Aged; Muramidase; Prognosis

Topics: Acute Disease; Adenosine; Aminohydrolases; Electrophoresis; Humans; Isoenzymes; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocytes; Muramidase; Mycosis Fungoides; Phenotype

Topics: Adult; Aged; Blood Urea Nitrogen; Female; Humans; Hypokalemia; Kidney Tubules; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Middle Aged; Muramidase; Myeloproliferative Disorders; Polycythemia Vera; Primary Myelofibrosis; Radiography; Spleen

Topics: Acute Disease; Adenine Nucleotides; Adenosine Diphosphate; Adult; Aged; Blood Platelets; Collagen; Epinephrine; Female; Fibrin; Humans; Kaolin; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Lymphoma, Non-Hodgkin; Male; Middle Aged; Muramidase; Platelet Adhesiveness; Remission, Spontaneous; Thrombin

Topics: Alkaline Phosphatase; Cell Transformation, Neoplastic; Humans; Leukemia, Myeloid, Acute; Muramidase; Neutrophils; Peroxidases

Topics: Adult; Aged; Blood Cell Count; Bone Marrow Cells; Bone Marrow Examination; Child; Cytarabine; Densitometry; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase; Remission, Spontaneous; Thioguanine; Vincristine

Topics: Acid Phosphatase; Alkaline Phosphatase; Cell Fractionation; Centrifugation, Density Gradient; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Monocytes; Muramidase; Neutrophils; Phagocytosis

A regimen of intravenous cyclophosphamide, cytarabine and vincristine, given over a four-day period and repeated every two to three weeks, was used to treat 33 patients with acute myeloblastic leukemia. Of the 30 evaluable patients 9/18 previously untreated patients achieved complete remission and two others marked improvement, and 4/12 previously treated patients achieved complete remission. Twelve of 16 patients under the median age of 38 responded while only 3/14 patients over this age responded. There was no difference in response between those with elevated muramidase levels and those with normal levels. Three patients developed a previously unrecognized syndorme of fever, malaise, rash and orbital suffusion. Cytarabine was probably responsible.At least four courses of treatment are required before abandoning this regimen of therapy. Patients who achieve a complete remission and live for more than 150 days spend about 25% of their total survival time from diagnosis in hospital.

Topics: Adult; Age Factors; Cyclophosphamide; Cytarabine; Evaluation Studies as Topic; Female; Hepatitis; Hepatitis B Antigens; Hospitalization; Humans; Injections, Intravenous; Leukemia, Myeloid, Acute; Male; Muramidase; Remission, Spontaneous; Vincristine

Topics: Clinical Enzyme Tests; Humans; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Muramidase

Topics: Acid Phosphatase; Adult; Aged; Bone Marrow Examination; Esterases; Female; Histocytochemistry; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Male; Microscopy, Electron; Muramidase; Skin Window Technique

Topics: Humans; Leukemia, Myeloid, Acute; Muramidase

Topics: Adult; Agranulocytosis; Alpha-Globulins; Beta-Globulins; Blood Cell Count; Blood Protein Electrophoresis; Bone Marrow Examination; Cobalt Isotopes; Cytarabine; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Muramidase; Periodicity; Protein Binding; Vitamin B 12

Topics: Acid Phosphatase; Alkaline Phosphatase; Amidohydrolases; Binding Sites; Culture Techniques; Diagnosis, Differential; Esterases; Female; Histocytochemistry; Humans; Immunoglobulin G; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Male; Microscopy, Electron; Monocytes; Muramidase; Oxidoreductases; Peroxidases; Skin Window Technique

Topics: Clinical Enzyme Tests; Diagnosis, Differential; Humans; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Monocytes; Muramidase; Prognosis

Topics: Acute Disease; Aged; Anemia; Blood Cell Count; Bone Marrow Examination; Diagnosis, Differential; Female; Hematocrit; Humans; Infections; Karyotyping; Leukemia; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Male; Middle Aged; Muramidase

Topics: Adult; Densitometry; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Muramidase; Remission, Spontaneous

Topics: Adolescent; Adult; Aged; Agranulocytosis; Allopurinol; Anti-Bacterial Agents; Antibiotics, Antineoplastic; Blood Transfusion; Cytarabine; Humans; Leukemia; Leukemia, Erythroblastic, Acute; Leukemia, Lymphoid; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Mercaptopurine; Methotrexate; Middle Aged; Muramidase; Nausea; Prednisolone; Thrombocytopenia; Vincristine

Topics: Adult; Bone Marrow Examination; Densitometry; Female; Hodgkin Disease; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocytes; Male; Methods; Muramidase; Spectrophotometry

Topics: Female; Humans; Leukemia, Erythroblastic, Acute; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Male; Monocytes; Muramidase; Myeloproliferative Disorders; Neutrophils; Precancerous Conditions

Topics: Bone Marrow; Bone Marrow Cells; Diagnosis, Differential; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid, Acute; Muramidase

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: Acid Phosphatase; Animals; Antigens; Cytoplasmic Granules; Esterases; Fluorescent Antibody Technique; Histocytochemistry; Humans; Hydrolases; Iron; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Macrophages; Monocytes; Muramidase; Rabbits; Skin Window Technique; Sodium

Topics: Animals; Blood Cells; Fluorescent Antibody Technique; Humans; Immune Sera; Immunodiffusion; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Monocytes; Muramidase; Rabbits; Species Specificity; Tears; Urine

Topics: Diagnosis, Differential; Humans; Leukemia, Monocytic, Acute; Leukemia, Myeloid, Acute; Monocytes; Muramidase

Topics: Adolescent; Adult; Female; Humans; Leukemia, Myeloid; Leukemia, Myeloid, Acute; Leukocyte Count; Leukocytes; Lymphocytes; Male; Monocytes; Muramidase

Topics: Amino Acids; Autoanalysis; Chromatography; Humans; Leukemia, Myeloid, Acute; Methods; Muramidase