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)

Generation of superoxide may be a key step in the cytotoxicity mediated by tumour necrosis factor (TNF); cells that cannot produce oxygen radicals might be resistant to TNF. Myeloid haemopoietic cells from patients with chronic granulomatous disease (CGD) cannot produce a large burst of oxygen radicals; therefore we examined the ability of TNF to inhibit clonal growth of myeloid haemopoietic cells from patients and carriers with several types of CGD. Mononuclear light-density cells from the peripheral blood of 13 CGD patients (11 patients with defects of gp91-phox and two with p47-phox), five gp91-phox carriers and 10 normal volunteers were cultured with the appropriate growth factor and TNF in methylcellulose. As expected, TNF (0.001-100 ng/ml) inhibited colony formation of myeloid cells of normal volunteers in a dose-dependent manner. In contrast, clonal growth of myeloid cells of CGD patients was resistant to inhibition by TNF < or = 100 ng/ml. As expected, the effects of TNF on erythroid clonogenic cells, which are not capable of producing an oxygen burst, and the action of TGF-beta on clonal growth of myeloid cells, were similar in both the individuals with CGD and the normal volunteers. In X chromosome-linked female carriers of CGD (gp91-phox deficiency), TNF showed an intermediate cytotoxicity on clonal growth of myeloid cells, and analysis of NBT reduction demonstrated that the colonies derived from myeloid cells deficient in gp91-phox were resistant to TNF and those derived from the myeloid cells expressing gp91-phox were inhibited in their proliferation by TNF. This study shows for the first time that myeloid haemopoietic cells from patients with CGD are relatively resistant to the growth-inhibiting effects of high concentrations of TNF.
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PMID:Myeloid haemopoietic cells of patients with chronic granulomatous disease are relatively resistant to TNF. 780 54

Chronic Granulomatous Disease (CGD) is an uncommon primary immunodeficiency caused by the absence or dysfunction of one of NADPH oxidase subunits, with heterogeneous genetic aetiologies. The aim of this study was the CGD patient registry in Greece, the identification of the responsible genotype and the potential correlation with the patient's clinical phenotype. Medical charts of 24 CGD patients, investigated by NBT test or DHR for NADPH oxidase activity, Western blot analysis for NADPH oxidase component expression and DNA sequencing (pyro- and cycle sequencing) for mutation analysis, were reviewed. All patients, but one, were classified into the different types of CGD. Sixteen patients from 14 unrelated families had X-linked CGD (66.7 %), four had mutations in the NCF1 gene (19 %), and three, from two unrelated families, had mutations in NCF2 (9.5 %) [Corrected]. Fifteen mutations were detected in the CYBB gene, including nonsense (53.8 %), splice site (30.8 %) and missense mutations (7.7 %), and deletions (7.7 %). Two novel mutations were identified; one in CYBB and one in NCF1. Carrier detection for X-CGD revealed that the de novo mutation rate was about 7 %. Prenatal diagnosis identified one affected male in three male fetuses tested. In both the X-linked and the autosomal recessive (AR-CGD) group, the gastrointestinal and respiratory manifestations were more common, followed by lympadenopathy in X-CGD and skin infections in the AR-CGD group. The patients with a mutation in CYBB had a wider variability of clinical manifestations and earlier diagnosis (4.6 years) compared to the AR-CGD group (12.9 years). The incidence of CGD in Greece is estimated at 0.90 (95 % CI 0.89-0.91) per 100,000 live births for the last decade.
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PMID:Chronic granulomatous disease: a 25-year patient registry based on a multistep diagnostic procedure, from the referral center for primary immunodeficiencies in Greece. 2408 83