muramidase and Multiple-Myeloma

B cells have limited endocytic capacity and are reported to endocytose and present liposome-encapsulated antigens poorly. B cells also endocytose soluble antigens poorly, except those for which their surface immunoglobulin is specific, which are taken up and presented efficiently. We present results indicating that, in vitro, B cells endocytose small liposomes bearing antigen with affinity for their surface immunoglobulin. Antigen encapsulated in liposomes targeted by antibody specific for surface immunoglobulin is presented to T cells as efficiently as specific antigen in soluble form. These studies provide a rational basis for the design of liposomes optimized to stimulate T-dependent B-cell responses.

Topics: Animals; Antigen Presentation; Antigens; B-Lymphocytes; Drug Carriers; Drug Compounding; Endocytosis; Liposomes; Lymphocyte Cooperation; Methotrexate; Mice; Mice, Nude; Mice, Transgenic; Multiple Myeloma; Muramidase; Rabbits; Receptors, Antigen, B-Cell; Tumor Cells, Cultured

Topics: Adult; Animals; Bence Jones Protein; Blood Urea Nitrogen; Calcium; Carcinoma; Electrolytes; Fanconi Syndrome; Humans; Kidney; Kidney Diseases; Leukemia; Lymphoma; Multiple Myeloma; Muramidase; Neoplasms; Nephrotic Syndrome; Phosphorus; Potassium; Proteinuria; Sodium

Topics: Amyloidosis; Blood Protein Disorders; Bone Neoplasms; gamma-Globulins; Humans; Karyotyping; Kidney Diseases; Kinetics; Leukemia; Leukemia, Lymphoid; Leukemia, Plasma Cell; Lung Neoplasms; Lymph Nodes; Lymphoma; Microscopy, Electron; Multiple Myeloma; Muramidase; Plasmacytoma

Topics: Bence Jones Protein; Humans; Immunoglobulin G; Immunoglobulins; Leukemia, Myeloid; Leukemia, Plasma Cell; Lymphoma; Multiple Myeloma; Muramidase; Proteins; Proteinuria; Waldenstrom Macroglobulinemia

Melphalan-based autologous stem cell transplant (Mel-ASCT) is a standard therapy for multiple myeloma, but is associated with severe oral mucositis (OM). To identify predictors for severe OM, we studied 381 consecutive newly diagnosed myeloma patients who received Mel-ASCT. Melphalan was given at 200 mg/m2 body surface area (BSA), reduced to 140 mg/m2 for serum creatinine >3 mg/dl. Potential covariates included demographics, pre-transplant serum albumin and renal and liver function tests, and mg/kg melphalan dose received. The BSA dosing resulted in a wide range of melphalan doses given (2.4-6.2 mg/kg). OM developed in 75% of patients and was severe in 21%. Predictors of severe OM in multiple logistic regression analyses were high serum creatinine (odds ratio (OR)=1.581; 95% confidence interval (CI): 1.080-2.313; P=0.018) and high mg/kg melphalan (OR=1.595; 95% CI: 1.065-2.389; P=0.023). An OM prediction model was developed based on these variables. We concluded that BSA dosing of melphalan results in wide variations in the mg/kg dose, and that patients with renal dysfunction who are scheduled to receive a high mg/kg melphalan dose have the greatest risk for severe OM following Mel-ASCT. Pharmacogenomic and pharmacokinetic studies are needed to better understand interpatient variability of melphalan exposure and toxicity.

Topics: Adult; Aged; Dose-Response Relationship, Drug; Drug Combinations; Female; Glucose Oxidase; Hematopoietic Stem Cell Transplantation; Humans; Incidence; Kidney Diseases; Lactoperoxidase; Male; Melphalan; Middle Aged; Models, Theoretical; Multiple Myeloma; Muramidase; Myeloablative Agonists; Predictive Value of Tests; Regression Analysis; Retrospective Studies; Risk Factors; Severity of Illness Index; Stomatitis; Transplantation Conditioning; Transplantation, Autologous

Whereas functional heavy (H)-chain antibodies devoid of light (L)- chains account for about half of the circulating immunoglobulins in Camelidae, H-chain only antibodies (HCAbs) are not produced in other healthy mammals including rodents and humans. To test the feasibility of expressing single chain antibodies in the mouse, which on account of their small size and antigen-recognition properties would have a major impact on antibody engineering strategies, we constructed a rearranged dromedary H-chain gene encoding the immunoglobulin G2a (IgG2a) isotype with specificity for hen-egg lysozyme (HEL). This IgG2a H-chain gene was introduced into mouse myeloma cells not expressing endogenous immunoglobulin H- or L-chains. Unexpectedly the mouse cells processed and expressed the introduced H-chain as naturally occurring dromedary antibody. For this the first constant (C) region exon was proficiently removed from the recombinant H-chain transcript. This resulted in specific H-chain antibodies of the correct molecular weight (2 x 50 000 MW) secreted as disulfide-linked homodimers and displayed on the mouse cell surface as glycosyl-phosphatidyl-inositol-linked B-cell receptor. The results indicate that antibody expression and maturation without immunoglobulin L-chain is feasible and paves the way for the generation of transgenic single chain antibody repertoires.

Topics: Animals; Antibody Specificity; B-Lymphocytes; Camelus; Feasibility Studies; Gene Rearrangement; Immunoglobulin G; Immunoglobulin Heavy Chains; Mice; Multiple Myeloma; Muramidase; Peptides; Species Specificity; Transfection

There is growing evidence that proteins are early targets of reactive oxygen species, and that the altered proteins can in turn damage other biomolecules. In this study, we measured the effects of proteins on the oxidation of liposome phospholipid membranes, and the formation of protein hydroperoxides in serum and in cultured cells exposed to radiation-generated hydroxyl free radicals. Lysozyme, which did not affect liposome stability, gave 50% protection when present at 0.3 mg/ml, and virtually completely prevented lipid oxidation at 10 mg/ml. When human blood serum was irradiated, lipids were oxidized only after the destruction of ascorbate. In contrast, peroxidation of proteins proceeded immediately. Protein hydroperoxides were also generated without a lag period in hybrid mouse myeloma cells, while at the same time no lipid peroxides formed. These results are consistent with the theory that, under physiological conditions, lipid membranes are likely to be effectively protected from randomly-generated hydroxyl radicals by proteins, and that protein peroxyl radicals and hydroperoxides may constitute an important hazard to biological systems under oxidative stress.

Topics: Animals; Ascorbic Acid; Dose-Response Relationship, Drug; Humans; Hydrogen Peroxide; Kinetics; Lipid Peroxidation; Lipids; Liposomes; Mice; Models, Chemical; Multiple Myeloma; Muramidase; Oxidative Stress; Oxygen; Proteins; Reactive Oxygen Species; Time Factors; Tumor Cells, Cultured

Topics: Aged; Bacillus subtilis; Bacteria; Escherichia coli; Female; Humans; Male; Micrococcus; Middle Aged; Multiple Myeloma; Muramidase; Pyelonephritis; Staphylococcus epidermidis

Topics: Adult; Aged; Female; Humans; Male; Middle Aged; Multiple Myeloma; Muramidase; Pyelonephritis

Fourteen patients with multiple myeloma (MM) were given chemotherapy courses for 7 days followed by 21-day intervals, combined with an immunomodulating treatment, namely lysozyme (LZM), 2 g daily for three weeks every other interval. Some parameters of cell-mediated immunity (total-E-rosettes, monocyte and polymorphonuclear leukocyte chemotaxis, skin tests) as well as humoral immunity (serum Ig levels, electrophoresis, immunoelectrophoresis) were evaluated comparatively in the intervals with and in those without LZM administration. A significant increase in total-E-rosettes and monocyte chemotaxis was observed in about half of the patients studied, this enhancement being accompanied by a reduction in both frequency and severity of viral and bacterial infections. No side-effects ascribable to LZM were recorded in any of the patients.

Topics: Adjuvants, Immunologic; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotaxis, Leukocyte; Drug Administration Schedule; Female; Humans; Immunity, Cellular; Immunoglobulins; Infection Control; Male; Middle Aged; Monocytes; Multiple Myeloma; Muramidase; Neutrophils; Rosette Formation; Skin Tests

In 42 myeloma patients our results confirm the association of light chain proteinuria and renal damage, but suggest that while the amount of light chain excreted is an important factor, only some light chains are nephrotoxic. The excretion of the proximal tubular cell lysosomal enzyme N acetyl B D glucosaminidase was a sensitive index of tubular injury, while the presence of low molecular weight proteinuria (Retinol Binding Protein and Lysozyme) was shown to indicate tubular dysfunction in a kidney sufficiently damaged to produce an impaired GFR. Isolated defects of distal tubular function (acid load response and concentrating ability) were rare. Such changes were seen mainly as part of global renal impairment and were usually associated with such specific pathophysiological conditions as plasma hyperviscosity or tubular crystal deposition. Hypercalcemia had a specific effect on the concentrating ability independent of any impairment of renal acidification.

Topics: Acetylglucosaminidase; Adult; Aged; Creatinine; Female; Glomerular Filtration Rate; Humans; Immunoglobulin Light Chains; Kidney Tubules; Kidney Tubules, Distal; Kidney Tubules, Proximal; Lysosomes; Male; Middle Aged; Multiple Myeloma; Muramidase; Proteinuria; Retinol-Binding Proteins; Retinol-Binding Proteins, Plasma

Topics: alpha-Macroglobulins; Female; Humans; Immunosuppression Therapy; Male; Monocytes; Multiple Myeloma; Muramidase

Staphylococcal protein A conjugated to horseradish peroxidase was employed in an indirect immuno-staining technique to identify intracellular antigens in paraffin-embedded tissues. The sections were incubated with specific antisera and the antigen-IgG complexes demonstrated with protein A-peroxidase conjugate. Immunoglobulins, lysozyme and insulin were satisfactorily detected by this technique. A comparison of this method with the PAP, "labelled antigen" and peroxidase-labelled antibody sandwich techniques was made.

Topics: Antigens; Bone Marrow; Histocytochemistry; Hodgkin Disease; Humans; Immunoenzyme Techniques; Immunoglobulins; Insulin; Lymph Nodes; Multiple Myeloma; Muramidase; Pancreas; Pancreatic Neoplasms; Staphylococcal Protein A

Lysozyme activity was determined in the serum, urine and leukocytes of 53 patients with immunocytoma and 24 patients with lymphoproliferative syndromes without associated monoclonal gammapathy. In patients with multiple myeloma the frequency of low serum lysozyme activity and high leukocyte lysozyme activity was higher. In the cases with renal failure, lysozyme activity was raised in serum and urine, and the 24-hour urinary lysozyme excretion was increased. In 7 patients with increased urinary lysozyme excretion no clinical or laboratory evidence of renal complications was found. Relative monocytosis in peripheral blood was observed in half of the cases of multiple myeloma, and in these patients also in about half of the cases the lysozyme activity was raised in the leukocytes and urine, and the 24-hour urinary lysozyme excretion was increased. In patients with Hodgkin's disease, lymphosarcoma and chronic lymphatic leukemia the frequency of low serum lysozyme activity was increased.

Topics: Adult; Aged; Humans; Kidney Diseases; Kidney Failure, Chronic; Leukocytes; Lymphoproliferative Disorders; Middle Aged; Multiple Myeloma; Muramidase; Waldenstrom Macroglobulinemia

Topics: Antigen-Antibody Reactions; Electrophoresis, Cellulose Acetate; Humans; Leukemia, Monocytic, Acute; Multiple Myeloma; Muramidase

SLL's were tested by turbidometric assay on 33 male patients with multiple myeloma with three to 58 tests (mean 11) for each patient over a 7-year period. The age of the patients ranged from 31 to 83 years, with a median age of 58 years. SLL's in the normal controls were 14.4 +/- 3.5 microgram/ml. Patients with myeloma had a median lysozyme level of 16 microgram/ml and mean of 16.5. The SLL's in patients with lgG1,2,3,4, Iga, and kappa and lambda light-chain myeloma were similar. Slightly higher mean SLL'S were noted in older patients. Patients with severe renal disease also had higher SLL'S. No significant changes in SLL's were seen during infections or during mild granulocytopenia (granulocyte count greater than 500 cells/mm3). In severe granulocytopenia (granulocyte count less than 500 cells/mm3) the SLL's decreased and returned to normal levels when the white blood cell counts improved. In eight patients surviving for more than 5 years, the SLL's were not different from those of the other patients. SLL values in patients with multiple myeloma did not differ significantly by statistical test from those of controls when those patients with impaired renal function are excluded.

Topics: Adult; Aged; Blood Cell Count; Humans; Immunoglobulin A; Immunoglobulin G; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Kidney Diseases; Male; Middle Aged; Multiple Myeloma; Muramidase

Topics: Animals; Hodgkin Disease; Humans; Hyperplasia; Immunoglobulin kappa-Chains; Immunoglobulin lambda-Chains; Lymphoma; Lymphoma, Follicular; Lymphoma, Non-Hodgkin; Multiple Myeloma; Muramidase

Intracellular lysozyme concentration was measured in neutrophilic granulocytes from 25 patients with multiple myeloma. At diagnosis intraneutrophil lysozyme activity was significantly reduced (mean reduction 50%). During clinical remission after 1-4 months of intensive chemotherapy values were normalized. In 18 cases studied at various stages of the disease from 6 to 70 months after diagnosis there was a significant negative correlation between the duration of the disease and neutrophil lysozyme concentration. The decrease in neutrophil lysozyme concentration was significantly correlated to clinical disease activity and the percentage of plasma cells in bone marrow aspirates, whereas there was no correlation between the concentration of M-protein in serum and the neutrophil lysozyme concentration. Plasma lysozyme concentration was normal. In contrast, neutrophil lysozyme concentration was normal in 18 patients with stage III-IV malignant lymphoma. Plasma lysozyme in this group was significantly higher than normal. The difference in neutrophil lysozyme patterns between multiple myeloma and malignant lymphoma supports the hypothesis that the defect in neutrophil maturation seen in malignant blood disorders is directly related to the infiltration of the bone marrow by pathologic cells.

Topics: Antineoplastic Agents; Bone Marrow Cells; Cell Division; Hodgkin Disease; Humans; Leukocyte Count; Leukocytes; Multiple Myeloma; Muramidase; Myeloma Proteins; Neutrophils

A reversible lysozymuria indicative of proximal tubular damage to the kidney was found in three out of five patients with diabetic ketosis, and a persistent lysozymuria was found in many patients with diabetic nephropathy. There was no relation between lysozymuria and the degree of proteinuria, and lysozymuria was not due to urinary tract infection. The degree of lysozymuria could be used to assess the severity of diabetic nephropathy.

Topics: Creatinine; Diabetic Nephropathies; Glomerulonephritis; Multiple Myeloma; Muramidase; Proteinuria; Pyelonephritis

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

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

Topics: Albumins; Animals; Antibody Specificity; Antigen-Antibody Complex; Binding Sites, Antibody; Centrifugation, Density Gradient; Chromatography, Gel; Chromatography, Ion Exchange; Colostrum; Epitopes; Humans; Immune Sera; Immunodiffusion; Immunoglobulin A; Immunoglobulin Fragments; Immunoglobulin G; Immunoglobulin Heavy Chains; Immunoglobulin J-Chains; Immunoglobulin M; Iodine Radioisotopes; Iodoacetates; Multiple Myeloma; Muramidase; Neurophysins; Polymers; Protein Binding; Rabbits; Species Specificity; Ultracentrifugation

Topics: Bence Jones Protein; Blood Protein Disorders; Creatinine; Humans; Immunoelectrophoresis; Immunoglobulin Fragments; Immunoglobulins; Kidney; Kidney Failure, Chronic; Kidney Transplantation; Metabolic Clearance Rate; Molecular Weight; Multiple Myeloma; Muramidase; Transplantation, Homologous

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: Adult; Anemia, Sideroblastic; Bone Marrow Diseases; Humans; Leukemia; Leukemia, Monocytic, Acute; Leukemia, Myeloid; Lymphoma; Monocytes; Multiple Myeloma; Muramidase; Polycythemia Vera; Primary Myelofibrosis

Topics: Arthritis, Rheumatoid; Electrophoresis; Humans; Kidney Diseases; Kidney Function Tests; Kidney Glomerulus; Kidney Tubules; Leukemia; Lupus Erythematosus, Systemic; Multiple Myeloma; Muramidase; Neoplasms; Proteinuria

Topics: Adenoma; Carcinoma; Creatinine; Dysgerminoma; Female; Humans; Kidney Neoplasms; Male; Multiple Myeloma; Muramidase; Ovarian Neoplasms; Pelvic Inflammatory Disease; Penile Neoplasms; Prostatic Hyperplasia; Prostatic Neoplasms; Urinary Bladder Neoplasms; Urogenital Neoplasms; Uterine Neoplasms; Vaginal Neoplasms

Topics: Bence Jones Protein; Blood Protein Disorders; gamma-Globulins; Heavy Chain Disease; Humans; Kidney Diseases; Kidney Tubules; Multiple Myeloma; Muramidase

Topics: Adult; Antibody Formation; Bence Jones Protein; Female; Humans; Immunoglobulin G; Leukemia, Myeloid; Male; Melphalan; Monocytes; Multiple Myeloma; Muramidase; Plasma Cells

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Female; Humans; Leukemia, Lymphoid; Leukemia, Myeloid; Leukocytes; Lymphoma; Male; Middle Aged; Multiple Myeloma; Muramidase; Sarcoidosis; Seasons

Topics: Candida; Candidiasis; Hodgkin Disease; Humans; In Vitro Techniques; Leukemia; Leukocytes; Lymphoma; Multiple Myeloma; Muramidase; Neoplasms; Neutrophils; Peroxidases; Phagocytosis; Polycythemia Vera

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: Adolescent; Adult; Arthritis, Rheumatoid; Body Fluids; Clinical Enzyme Tests; Female; Humans; Leukemia; Leukemia, Lymphoid; Leukemia, Myeloid; Male; Middle Aged; Multiple Myeloma; Muramidase; Pregnancy; Synovial Fluid; Waldenstrom Macroglobulinemia

Topics: Bence Jones Protein; Beta-Globulins; Carbohydrates; Chemical Phenomena; Chemistry; Chromatography; Electrophoresis; gamma-Globulins; Hemoglobins; Hot Temperature; Immunochemistry; Immunodiffusion; Immunoelectrophoresis; Multiple Myeloma; Muramidase; Ovalbumin; Pepsin A; Polymers; Ribonucleases; Serum Albumin; Serum Globulins; Transferrin; Trypsin