Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.6.99.3 (diaphorase)
 5,903 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biologic basis for the elevated histochemical reduction of nitroblue tetrazolium dye (NBT) in neutrophils from patients with acute bacterial infection or polycythemia vera was studied. A precipitin reaction followed mixing NBT with heparin. NBT was reduced after phagocytosis of this complex (H-NBT) by polymorphonuclear leukocytes (PMNs). Ingestion required divalent cations and was facilitated by the presence of complement. H-NBT incubated with normal but not with C2-deficient human serum converted native C3 to its inactive form. Phagocytic indices were determined in patients and controls by measuring O(2) utilization and hexose monophosphate shunt activity and by visually counting cell-associated latex particles. Significant elevations above controls were observed in phagocytes isolated from all patients with elevated histochemical NBT scores when H-NBT complex, latex, or zymosan was employed as the phagocytic particle. Increased indices were observed in the presence of fresh AB serum, heat-inactivated AB serum, or without serum. Serum from patients with elevated NBT scores did not alter phagocytosis in control phagocytes. With NADH and NADPH as substrates, total NBT diaphorase activity of sonicated leukocytes was normal in all patients. These results suggest that increased phagocytic capacity of PMNs is the primary cause of increased histochemical NBT reduction. The PMNs of patients with acute bacterial infection or polycythemia vera may have alterations in their cell membranes which lead to an enhanced rate of phagocytosis.
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PMID:Enhanced phagocytic capacity. The biologic basis for the elevated histochemical nitroblue tetrazolium reaction. 415 97

Somatic mutations have a role in the pathogenesis of a number of diseases, particularly cancers. Here we present data supporting a role of mitochondrial somatic mutations in an autoimmune disease, rheumatoid arthritis (RA). RA is a complex, multifactorial disease with a number of predisposition traits, including major histocompatibility complex (MHC) type and early bacterial infection in the joint. Somatic mutations in mitochondrial peptides displayed by MHCs may be recognized as non-self, furthering the destructive immune infiltration of the RA joint. Because many bacterial proteins have mitochondrial homologues, the immune system may be primed against these altered peptides if they mimic bacterial homologues. In addition, somatic mutations may be influencing cellular function, aiding in the acquirement of transformed properties of RA synoviocytes. To test the hypothesis that mutations in mitochondrial DNA (mtDNA) are associated with RA, we focused on the MT-ND1 gene for mitochondrially encoded NADH dehydrogenase 1 (subunit one of complex I - NADH dehydrogenase) of synoviocyte mitochondria from RA patients, using tissue from osteoarthritis (OA) patients for controls. We identified the mutational burden and amino acid changes in potential epitope regions in the two patient groups. RA synoviocyte mtDNA had about twice the number of mutations as the OA group. Furthermore, some of these changes had resulted in potential non-self MHC peptide epitopes. These results provide evidence for a new role for somatic mutations in mtDNA in RA and predict a role in other diseases.
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PMID:Somatic mutations in the mitochondria of rheumatoid arthritis synoviocytes. 1620 43