Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The activities of N-acetyl-beta-D-glucosaminidase (NAG), gamma-glutamyl-transpeptidase (gamma-GTP) and NAG isoenzyme were measured in the urine of 20 patients with multiple myeloma (IgG/IgA type/Bense Jones type; 15/1/4 cases) and 25 healthy controls to evaluate these activities as indicators of renal disturbance in multiple myeloma. NAG isoenzyme fractions in urine were measured by agarose electrophoresis-m-cresol sulfonphthaleinyl-NAG reaction. Mean urinary NAG activity in the patients with myeloma was significantly higher than that in the controls (20.1 +/- 3.3 vs 4.3 +/- 0.3U/g. cr; p < 0.001). Urinary NAG activity in these patients correlated positively with the dose (mg/g. cr) of urinary protein (r = 0.755; p < 0.01), most of which were considered to be light chain protein, but not with creatinine clearance. Each urinary NAG isoenzyme fraction (NAG-1, -2, -3) was higher in the patients than that in the controls, and especially NAG-2 fraction (A form) showed a highly positive correlation with the dose of urinary protein. Urinary gamma-GTP activity in the patients did not differ from that in the controls, but urinary NAG/gamma-GTP ratio was higher in the patients, and reversely correlated with creatinine clearance (r = -0.721; p < 0.01). It is suggested that the elevation of urinary NAG activity results from the damage of lysosome in proximal tubular cells by urinary light chain protein and its degradation products. Therefore, urinary NAG activity may be a good index for proximal tubular disturbance, and NAG/gamma-GTP ratio may be an index for the extensive damage of nephrons in addition to the damage of tubular cells in multiple myeloma.
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PMID:[Urinary N-acetyl-beta-D-glucosaminidase and gamma-glutamyl-transpeptidase activities for evaluation of renal disturbance in patients with multiple myeloma]. 136 43

The renal tubular lesion induced by human Bence Jones proteins (BJPs) in the rat was investigated to elucidate the initial role of BJPs in the genesis of renal tubular damage in myeloma kidney. Human BJP extracted from the urine collected from a patient with lambda light chain myeloma was given intraperitoneally to Sprague-Dawley rats with a daily dose of 300 mg/day for 5 days (BJP group, n = 16). Daily urinary excretion of N-acetyl-beta-D-glucosaminidase (NAG), which may represent the intensity of tubular damage, was measured. On days 10 and 20 after start of the injection, the kidneys were removed and examined by light and electron microscopy. The renal content of NAG was also measured to estimate the lysosomal activity. Both urinary and renal tissue NAG were significantly higher in the BJP group than in control rats injected with bovine serum albumin (n = 16). The most characteristic changes were found in the proximal tubules of the BJP group; the number and size of lysosomes were increased, and some showed enlargement with autophagic vacuolation. However, these were not found in the control group. There were no obvious changes in the distal tubules in either group, and the glomeruli appeared to be intact. These results suggest that BJP directly damages the proximal tubules via the process of catabolism, resulting in injury to these cells, and that the urinary NAG is a sensitive marker to detect early tubular damage by BJP.
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PMID:Renal tubular lesions induced by human Bence Jones protein in the rat: N-acetyl-beta-D-glucosaminidase as a sensitive marker. 184 54

Human alveolar macrophages were obtained during diagnostic bronchoalveolar lavage. Cells were cultured, and morphological examination (including electron microscopy) revealed that not more than 5% of the cultured cells were identifiable as cells other than alveolar macrophages. The cells were sensitized with human myeloma immunoglobulin E. and then challenged with anti-immunoglobulin E anti-sera. The experiments employed a highly specific monoclonal antibody and three affinity purified reagents. The formation of immunoglobulin E/anti-immunoglobulin E complexes facilitated release from alveolar macrophages of leukotriene B4, prostaglandin F2 alpha, thromboxane B2 and the lysosomal hydrolase N-acetyl-beta-D-glucosaminidase. There was no release of active oxygen species, with this stimulus, as measured by lucigenin chemiluminescence. Immunoglobulin E receptors were identified histochemically on the surface of human alveolar macrophages, and were visualized as conjugates with colloidal gold by electron microscopy. These results support the view that human alveolar macrophages may contribute to type 1 hypersensitivity reactions in the lung.
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PMID:Immunoglobulin E-dependent stimulation of human alveolar macrophages: significance in type 1 hypersensitivity. 294 65

Sodium cromoglycate is an effective prophylactic in the treatment of asthma. However, its mechanism of action is still uncertain. The release of thromboxane B2 and N-acetyl-beta-D-glucosaminidase activity was measured from human alveolar macrophages sensitized with human myeloma IgE. Cells were challenged with rabbit affinity purified anti-IgE (no activity against IgG) in the absence or presence of sodium cromoglycate (10(-4)-10(-8)M). There was no change in the release of either thromboxane B2 or N-acetyl-beta-D-glucosaminidase in the presence of sodium cromoglycate at these concentrations.
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PMID:Stimulation of IgE sensitized human alveolar macrophages by anti-IgE is unaffected by sodium cromoglycate. 309 49

The activity of the lysosomal hydrolase N-acetyl-beta-D-glucosaminidase (NAG) was measured in the urine of patients with leukaemia or myeloma. Elevated pre-treatment enzymuria was noted in all patient groups with acute myeloblastic leukaemias (AML) FAB type M4 or 5 displaying higher activities than AML patients FAB types M1-3, which in turn were higher than those found in patients with myelomatosis and chronic lymphocytic leukaemia. The ratio of the major isoenzymes of NAG, A/B was reduced significantly only in patients with AML. Following treatment, AML patients who entered remission demonstrated NAG levels which approached normal values. In those AML patients who were either in relapse, in the terminal phase of their illness or treated with aminoglycoside antibiotics, NAG enzymuria was similar to pre-treatment values. A reduction in urinary NAG levels and both serum and urine beta 2 microglobulin concentrations was also observed following treatment in myeloma patients. The use of enzymuria both as a guide to progress towards remission in AML patients and for assessing prognosis and progress in myeloma patients is discussed.
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PMID:N-acetyl-beta-D-glucosaminidase enzymuria in leukaemia and myelomatosis: effect of treatment in acute myeloblastic leukaemia and myelomatosis in adults. 346 45

The isoenzyme profiles of hexosaminidase (N-acetyl-beta-D-glucosaminidase) were analyzed by isoelectric focusing on horizontal polyacrylamide thin-layer gel with special emphasis on the intermediate isoenzyme (Hex I). The expression of Hex I was examined in 87 leukemia-lymphoma cell lines, in 14 B-lymphoblastoid cell lines, in 441 cases of leukemia-lymphoma (specimens containing 80% or more tumor cells), in 22 leukemia cell lines and in 14 cases of leukemia that had been treated with phorbolesters (TPA) for induction of differentiation, and in the mononuclear cell preparations separated from peripheral blood, lymph node, thymus, bone marrow, tonsil, liver, and spleen specimens from normal donors. Hex I was detected in the leukemia cell lines arrested at early, immature or at late, mature stages of B- and T-cell differentiation, but not in cell lines blocked at intermediate stages of maturation. Most myelomonocytic leukemia cell lines and the erythroleukemia cell lines showed Hex I, whereas the B-lymphoblastoid cell lines were negative for this marker. During induction of differentiation, the expression of Hex I was lost in 13 of 15 leukemia cell lines that were originally Hex I-positive. Among the panel of the "fresh" leukemia-lymphoma cells, Hex I was found predominantly in cases of acute lymphoblastic leukemia and acute myeloblastic/monoblastic leukemia, but rarely or not at all in the mature T-, B- or myeloid malignancies. However, two out of two cases of multiple myeloma were Hex I-positive, and the Hex I expression could be induced by TPA in three of six B-cell chronic lymphocytic leukemia cases. Chronic myelocytic leukemia cells remained Hex I-negative during induction of differentiation. Hex I-positivity was not detected in the cell preparations from normal tissues, and peripheral blood indicating that the normal cellular counterpart of the Hex I-positive tumor cells are present at only low percentages within the respective cell populations. It is suggested that Hex I is a marker of early lymphoid and myeloid hematopoiesis that is no longer expressed in intermediate stages of lymphoid differentiation and in later or terminal stages of myeloid differentiation, but that is again detectable in terminally differentiated B-cells. Further studies will focus on identification and isolation of normal Hex I-positive cells.
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PMID:Occurrence of particular isoenzymes in fresh and cultured leukemia-lymphoma cells. II. Hexosaminidase I isoenzyme. 348 78

We describe the nephrotoxic effects of a preparation of light chains (LC) obtained by reduction and alkylation of human IgG. The acute renal lesions in rats are dependent upon the dose and route of LC administration. The kidney alterations were not observed in animals treated with comparable amounts of human albumin or the F(ab')2 fragment of human IgG. Intravenous bolus injection of 120 mg LC into 80-100 g hydropenic rats induced extensive cast formation in distal and collecting renal tubules, which were similar to the human "myeloma kidney". In contrast, the slow infusion of the same amount of LC over 1 h produced degenerative changes in the proximal tubular cells without extensive cast formation. The morphological alterations of the kidney were investigated by classical histological methods, by immunofluorescence and in thin sections stained with toluidine blue. Urinary excretion and kidney content of the lysosomal enzyme N-acetyl-beta-D-glucosaminidase were increased only in the group of animals infused with LC. These findings may be relevant to the pathogenesis of human nephropathy occurring in multiple myeloma and in some autoimmune diseases.
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PMID:Experimental nephropathy induced by human polyclonal light chains. 393 5

In 34 patients with multiple myeloma we have studied urinary N-acetyl-beta-D-glucosaminidase (NAG) as an index of tubular injury and related it to urinary light chain excretion and serum creatinine. Our results confirm the association of light chain proteinuria with both tubular damage and global renal impairment, but show that not all light chains are nephrotoxic. Tubular damage occurs independently of global renal impairment. Clinically, urinary NAG appears to be a useful index of early tubular damage in multiple myeloma.
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PMID:Urinary N-acetyl-beta-D-glucosaminidase as an indicator of tubular damage in multiple myeloma. 642 24

A prospective study was undertaken of 15 patients with impaired renal function undergoing x-ray procedures entailing the use of contrast material to see whether any deterioration in renal function resulted. Patients with diabetes or myelomatosis were excluded. Detailed observations were made during three days before and after the x-ray procedure to detect any change in factors such as fluid state, drug treatment, infection, or diet which might have affected renal function. No significant changes occurred in endogenous creatinine and 51Cr-EDTA clearances, or in plasma creatinine and urea concentrations after the x-ray procedures. Furthermore, there was no change in urinary activity of N-acetyl-beta-D-glucosaminidase, which is a highly sensitive indicator of renal parenchymal damage. Provided that fluid depletion and multiple x-ray procedures with radiocontrast material in rapid sequence are avoided, these procedures do not appear to affect renal function adversely, even when renal disease is advanced.
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PMID:Effect of radiocontrast media on kidneys of patients with renal disease. 678 30