Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02003 (NBT)
 1,323 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A polarographic method to assess the scavenging capacity of a molecule for O2-. is proposed. This method is based on the fact that O2-. is not detected by the Clark electrode and that a scavenger competes with spontaneous dismutation of O2-. So, the reduction of O2 into O2-. and the decomposition of H2O2 by catalase, releasing O2, show a biphasic kinetic. Various kinetic parameters can be used to calculate the nmol of O2-. scavenged and also supply data on the reaction mechanisms (oxidation or reduction of O2-.) involved in scavenging. This method presents several other advantages: scavenging capacity can be assayed without added indicators which themselves behave as scavengers (as demonstrated for NBT), the presence of scavengers which interfere with the O2-. generating system (xanthine-xanthine oxidase) does not invalidate the measurements made.
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PMID:Superoxide anion scavenging capacity measured by a polarographic method. Comparison with a colourimetric method. 133 24

A 19-year-old male was diagnosed as having chronic granulomatous disease (CGD) based on negative NBT reduction in January, 1988. He was admitted with a chief complaint of high fever in November, 1988. As abdominal echogram and CT scan established a diagnosis of multiple hepatic abscesses, he was treated with various kinds of antibiotics. Since the therapy was ineffective, the number of circulating neutrophils was decreased, and the abscesses further grew, intravenous drip infusion of rhG-CSF 100 micrograms was initiated in addition to several antibiotics (sulfamethoxazole-trimethoprim, rifampicin, isoniazide, etc). At day 3 on rhG-CSF, the fever began to resolve and on day 15 the body temperature fell below 37 degrees C. The hepatic abscesses also tended to decrease in size and the CT scan performed 2 months later (March 17), disclosed only calcification in the liver. The neutrophil function test indicated that superoxide anion (O2-) and hydrogen peroxide (H2O2) production was slightly increased during rhG-CSF therapy. Combination therapy with rhG-CSF and potent antibiotics showed a favorable therapeutic effect on CGD complicated by multiple hepatic abscesses as a fatal infection.
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PMID:[Effect of rhG-CSF in the treatment of multiple hepatic abscesses in chronic granulomatous disease]. 170 Oct 9

Pregnant randombred ICR mice were administered 2.5 or 5.0 mg/kg body weight of CdCl2 on day 16 of pregnancy and immune responses of their offspring were tested postnatally. At the age of 4 weeks, proliferative responses of spleen cells to concanavalin A, phytohemagglutinin and lipopolysaccharide and the background proliferation were enhanced in both experimental groups. The activation index was increased only after activation with concanavalin A and lipopolysaccharide in the group treated by the dose 5 mg/kg. The delayed type hypersensitivity to sheep red blood cells after immunization at 4 weeks was decreased. The serum IgM antibody response to sheep red blood cells was increased in the offspring of females treated with the lower dose of cadmium both at week 4 and 8. Activity of peritoneal macrophages (NBT, H2O2) was enhanced at 4 weeks and lowered subsequently. It is concluded that in mice the maternal exposure to a single dose of cadmium results in postnatally manifested deviations of immune functions of their offsprings.
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PMID:Developmental toxicity of cadmium in mice. II. Immunotoxic effects. 181 May 12

It has been shown that H2O2, the dismutation product of O2., is produced at cell-surface interfaces. Nevertheless, the relationships between the degree of attachment itself, type of surface, and O2. production are not clear. Superoxide production can be measured by the O2.-dependent reduction of nitroblue tetrazolium to an insoluble formazan. Superoxide dismutase (SOD) may be unable to scavenge O2. produced between alveolar macrophages (AM) and a surface. Desferal-Mn(IV) (Des-Mn), a low molecular weight mimic of SOD, is protective against paraquat toxicity in vivo, presumably because of specificity for O2-. Using that assumption, Des-Mn was used to measure O2. production that occurred during adherence of AM. AM suspensions were placed on fibronectin-coated glass coverslips or uncoated glass coverslips or non-stick tissue culture plates. Adherence to the surfaces varied with fibronectin greater than glass greater than non-stick and the percent formazan positive cells was 60, 24, and 4, respectively. With SOD present, the percentage of formazan positive cells were 40, 17, and 2; however, in the presence of Des-Mn the percent stained cells was 4, 4, and 0. When phorbol myristate acetate (PMA) was added during adherence, the percent of formazan positive cells was 82, 57, and 44, respectively. With PMA, Des-Mn was able to inhibit 88-100% of formazan staining whereas SOD inhibition decreased more markedly with increasing adherence. These results indicated that the degree of attachment correlated with both the degree of NBT reduction and the relative effectiveness of Des-Mn versus SOD to scavenge O2..
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PMID:Adhering lung macrophages produce superoxide demonstrated with desferal-Mn(IV). 254 53

Serum ferritin levels are often elevated in patients with certain cancers and these elevations are, in part, derived from the tumors. In such patients, the increased levels of serum ferritin are associated with a poor prognosis. This association may be explained in part by biological effects of ferritin on lymphocytes: inhibition of E-rosette formation, masking of cell surfaces and suppression of lymphocytes' response to mitogens in vitro. The authors hypothesized that ferritins from tumor tissues also exert adverse effects on human granulocytes that are involved in tumoricidal activity. Three granulocyte functions were tested: nitroblue tetrazolium test, phagocytosis, and production of hydrogen peroxide. The results supported the authors' hypothesis: NBT reduction and phagocytosis are decreased in granulocytes exposed to ferritins, more so with tumor ferritins, than normal ferritin, and H2O2 production is less in granulocytes previously exposed to ferritins from tumor and nontumor tissues than cells not exposed to ferritins. However, the inhibitory effects of ferritins on H2O2 production can be reversed if granulocytes are further stimulated by phorbol myristate acetate (a membrane stimulant). If the elevated serum ferritin in cancer patients impairs granulocyte functions, in vivo, then it may increase the risk of infection, decrease tumoricidal host responses, and, thereby, contribute to the poor prognosis of these individuals.
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PMID:Effects of isoferritins on human granulocytes. 272 May 99

Human myeloid leukemia cells respond to various signals by differentiating to more mature cells. This study was designed to evaluate the effects of a mononuclear phagocyte-derived factor, tumor necrosis factor/cachectin (TNF), on the proliferation and differentiation of the human cell lines HL-60 (promyelocytic) and U937 (monoblastic), and to characterize TNF receptors on these cells. TNF had no effect on HL-60 cell growth or thymidine incorporation, but it markedly inhibited that of U937 cells. HL-60 cells treated with TNF formed osteoclast-like polykaryons and developed nonspecific esterase positivity. In a dose-dependent fashion, TNF enhanced HL-60 cell nonspecific esterase activity, H2O2 production, NBT reduction, and acid phosphatase content. Together, TNF and interferon-gamma (IFN-gamma) additively and synergistically caused increases in these activities as well as the expression of HLA-DR and the monocyte antigens LeuM3 (CDw14) and OKM1 (CD11). TNF also synergistically enhanced the differentiating effects of 1,25-dihydroxyvitamin D3. The potentiating actions of D3 of IFN-gamma on the TNF effect were maximal when the two agents were present together throughout the incubation, and pretreatment with TNF augmented the subsequent response to D3, but not IFN-gamma. HL-60 and U937 cells bound 125I-labeled TNF specifically, rapidly, and reversibly with binding constants of 227 and 333 pmol/L and receptors per cell of 4,435 and 6,806 for HL-60 and U937, respectively. Scatchard plots were linear, which suggested single classes of receptors. HL-60 TNF receptors were not changed by a three-day treatment with IFN-gamma or D3. U937 and HL-60 cells internalized and degraded 125I-labeled TNF to comparable degrees. TNF has differing effects on HL-60 and U937 cells that are apparently mediated through comparable high-affinity TNF receptors. The unique responses of different cell types to TNF may be due to postreceptor factors.
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PMID:Receptor-mediated monocytoid differentiation of human promyelocytic cells by tumor necrosis factor: synergistic actions with interferon-gamma and 1,25-dihydroxyvitamin D3. 282 May 33

Poly-L-histidine (PHSTD) of molecular weight 26,000 induced the generation of large amounts of superoxide (O2-) and hydrogen peroxide (H2O2) in human neutrophils (PMNs). Despite its low solubility at neutral pH, PHSTD was bound very rapidly to the PMN surfaces. Maximal generation of O2- took place with 4-5 X 10(-6) M of PHSTD, starting after a lag of about 25 sec and proceeding for 15-17 min at a rate of 150 nmol/10(7) PMNs/min, suggesting that this polycation is one of the most potent stimulators of O2- generation known, PHSTD was found to be non-toxic for PMNs even at millimolar concentrations. Generation of O2- by PHSTD depended on extracellular calcium; it was inhibited by calcium channel blockers and by trifluoperazine, and it triggered a sharp rise in intracellular calcium as determined by the Quin 2 fluorescence technique. The generation of both O2- and H2O2 by PHSTD was partially inhibited by cytochalasin B or (CYB, CYE). On the other hand, CYB markedly enhanced the generation of both O2- and H2O2 following stimulation of PMNs either by PHSTD, polyarginine, histone, or by antibody-opsonized group A streptococci. Electron microscopic analysis and NBT reduction tests revealed that both PHSTD and PHSTD-opsonized streptococci were avidly phagocytosed by PMNs. Since CYB totally inhibited internalization of both PHSTD and the PHSTD-opsonized streptococci, it was suggested that these agents stimulated oxygen radical generation mainly on the leukocyte surfaces. Complexes (CX) formed between PHSTD and polyanethole sulfonate (a strong polyanion) or between histone and the polyanion mimicked immune CX in their ability to trigger the generation of large amounts of O2- which were inhibited by CYB. Generation of O2- and chemiluminescence either by PHSTD or by PHSTD-opsonized streptococci were markedly inhibited by poly-L-glutamate, suggesting that PHSTD acted as a cationic agent which interacted via electrostatic forces with some negatively charged sites in the leukocyte membrane. Generation of H2O2 by PHSTD was also markedly inhibited by deoxyglucose, KCN, DASA, as well as by the lipoxygenase inhibitors nordihydroguaiaretic acid, phenidone, and propylgallate. On the other hand, cyclooxygenase inhibitors such as aspirin, indomethacin, and piroxicam were inactive, suggesting that arachidonic acid metabolism via lipoxygenase pathway might have been involved in the activation by PHSTD of the NADPH oxidase in PMNs.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Poly L-histidine. A potent stimulator of superoxide generation in human blood leukocytes. 282 Aug 76

Carrageenan, a sulfated polyanionic polysaccharide, is commonly used to induce inflammation in experimental animals, and this model is used to screen for the effectiveness of antiinflammatory drugs. Carrageenan-induced inflammation has been attributed to a variety of autocoids including histamine, bradykinin, complement, superoxide, and prostaglandins. This study examines the effects of carrageenan on human PMN in a serum-free system. Carrageenan was found to stimulate the reduction of NBT by PMNs without stimulating membrane depolarization, oxygen consumption, H2O2 production, or myeloperoxidase secretion. Carrageenan stimulates a heat-labile, NBT-reducing system which is unassociated with the usual stimulus-response coupling seen with other PMN activators such as PMA, FMLP, and zymosan.
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PMID:Carrageenan stimulates reduction of nitroblue tetrazolium by human neutrophils without membrane depolarization, myeloperoxidase secretion, or increased oxygen consumption. 302 93

Rainbow trout head kidney and blood leucocytes are shown to be capable of secreting a soluble macrophage-activating factor (MAF) after stimulation with concanavalin A (Con A). The presence of phorbol myristate acetate (PMA) as a co-stimulant increased the production of MAF. Both respiratory burst activity (nitroblue tetrazolium, NBT, reduction and H2O2 production) and bactericidal activity were enhanced after incubation of resident or elicited macrophages with the MAF-containing supernatants for 48-72 hr. The target culture period before the addition of MAF did not affect their responsiveness, but a continuous presence of MAF was necessary for maximal stimulation.
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PMID:The production of a macrophage-activating factor from rainbow trout Salmo gairdneri leucocytes. 305 54

The effect of EDTA and H2O2 on iron autoxidation in Mops buffer depends on the pH of the solution. At acidic pH, EDTA caused the oxidation of a stoichiometric amount of iron. At neutral and alkaline pH, EDTA and H2O2 not only oxidizes a stoichiometric amount of iron but also causes the oxidation of the Fe2+ exceeding the concentration of these compounds. In the presence of EDTA, oxidation of Fe2+ in exceeding the concentration of these compounds has a shorter lag phase and an increased rate compared with that in the absence. The solution develops a yellow colour whose intensity is proportional to the amount of Fe2+ exceeding the concentration of these compounds in solution. When the reaction is conducted in the presence of NBT, formazan formation is greatly reduced compared to the control without EDTA and H2O2. The Fe3+-EDTA complex and Fe3+ affected iron oxidation, development of the yellow colour and NBT reduction in a similar fashion. In all these experimental conditions, iron oxidation is greatly reduced in the presence of mannitol, sorbitol and catalase. In phosphate buffer, EDTA oxidized a stoichiometric amount of iron without affecting free Fe2+ oxidation. Fe3+ has no effect on iron oxidation in this buffer.
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PMID:Iron oxidation in Mops buffer. Effect of EDTA, hydrogen peroxide and FeCl3. 314 95


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