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)

Chronic granulomatous disease (CGD) is characterized by frequent uncontrollable infections which often lead to death in early childhood. The first clinical signs may be confined to the skin and manifest themselves as abscesses, pyoderma, eczema or draining sinuses. Frequently, lymph nodes, spleen, lungs or liver are also involved. The basic defect is a failure of leukocytes to kill certain bacteria or fungi. The exact biochemical defect is however not yet known. The diagnosis of CGD is based on the clinical picture and on a defect of the granulocytes, as proven by bactericidal, NBT-reduction or chemiluminescence tests. In most and possibly in all of the cases, the disease is X-linked, and the CGD-gene has been regionally assigned to the X-chromosome. The existence of a second type of CGD with autosomal recessive inheritance has been assumed by several authors. In order to improve the prognosis of CGD, it is essential that the disease is diagnosed as early as possible so that prompt treatment can be given.
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PMID:[Clinical course and pathomechanisms of chronic granulomatosis]. 672 5

Six cases of chronic granulomatous disese (CGD), three of which correspond to the X-linked genetic form and the three other to the autosomic recessive type are reported. The fact of half of the patients being females is relevant as only 24 are cited by Klebanoff and Clark in their revision in 1978. X-linked CGD: The three patients, two of them brothers, presented their first manifestations in the first year of life; in one of the BCG given at one week of life resulted in adenitis of protracted course with calcificaton. The clinical course has been very severe in two of them. At the present time the patients are 15, 11 and 9 years old. Functional studies have shown very low values in NBT tests, O2 consumption, iodination and bactericidal activity in all three. Intermediate values in the mothers and normal values in the fathers were found. Autosomal CGD: Of our three patients, two were sisters. The first manifestations appeared during the first thrimester of life. The eldest had hepatic and pulmonary granulomata at three years old. At five years, she presented an intestinal obstruction syndrome with gastric antral, duodenal and ileal stenosis caused by intramural granulomata and inflammation; she died of pneumonia shortly after. Her sister had dermatitis, hepatic abscess, pneumonia, adenitis and osteomyuelitis of the ribs; she died at six years old after a bronchopneumonia. Last patient had a sister who died at two years old affected probably gy CGD. At present our patient is 17 months old and so far had recurrent otitis, adenitis, a pneumonia and, recently, hepatic granulomata have been found. Fonctional studies in the two sisters showed similar alterations as those of the three boys. In this patient an alteration of chemotaxis of cellular origen was found as well.
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PMID:[Chronic granulomatous disease: clinical and functional studies in six cases (author's transl)]. 740 65

Neutrophils from 50 pediatric patients with normal phagocyte functions, from 150 healthy adults, from 10 chronic granulomatous disease (CGD)-patients (4 CGD+), and from 18 X-linked carriers for CGD have been tested for their production of H2O2 using staining with dihydrorhodamine 123 and subsequent flow cytometry. Additionally, neutrophils from three patients with myeloperoxidase deficiency were assessed. Cells were activated to produce H2O2 by the phorbol ester phorbol-myristate-acetate (PMA) and by phagocytosis of Escherichia coli bacteria. To evaluate the sensitivity of the method, H2O2-production by neutrophils which was inhibited by different concentrations of diphenyljodonium (DPI) was measured. The results were compared to those from other methods (NBT-testing, cytochrome c-reduction, and especially chemiluminescence). Normal values and ranges of scatter profile were evaluated in terms of peak channel fluorescence: 97% > 700, x = 840 +/- 59 (S.D.), 97% < 890, for pediatric patients. Normal quantitative values also resulted from small blood samples of infants (< 1 year, n = 6, x = 830 +/- 52). For CGD+ (n = 4) the results were clearly far below the normal range. In indicating decreased production of reactive oxygen intermediates the method was at least as sensitive as lucigenin enhanced chemiluminescence. Cytochrome b558-expression of neutrophils from patients and healthy controls was established by flow cytometry following staining with the monoclonal antibody 7D5. The normal range was 97% > 485, 97% < 680, peak channel fluorescence. We conclude that flow cytometric routine diagnostics of CGD can easily enhance the reliability of recognition and the yield of information about this disease compared to conventional methods.
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PMID:Evaluation of flow cytometric methods for diagnosis of chronic granulomatous disease variants under routine laboratory conditions. 781 34

We report six new cases of chronic granulomatous disease (CGD) diagnosed at our service. The cases represent 1.1% of all primary immunodeficiencies diagnosed. Four of the children were boys and two were girls. The hereditary mechanism was X-linked in three cases and autosomal recessive in the other three. Clinical manifestations appeared before the age of 2 years in all cases; the illness appeared earlier in males, and was more severe, consisting of bacterial infections such as abscesses in the liver, lungs or skin, suppurating lymphadenitis and mastoiditis. None of the patients had osteomyelitis. The germs isolated were bacteria (Staphylococcus, Salmonella, Serratia, Pseudomonas, Enterococcus) and fungi (Candida, Aspergillus, Trichopyton). Orientative complementary evidence was intense leukocytosis, high levels of acute phase reactants (PCR and VSG), polyclonal hypergammaglobulinemia and high LB ant LT4 levels. Definitive diagnosis was provided by the NBT test and chemiluminescence in all cases.
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PMID:Chronic granulomatous disease: six new cases. 988 32

Our laboratory has reported the correction of neutrophil NADPH oxidase function by retroviral-mediated gene transfer (RMGT) in murine X-linked chronic granulomatous disease (X-CGD). Few studies, however, have used nonmyeloablative conditioning in conjunction with RMGT. Promising methods of decreased intensity conditioning include low dose irradiation and antimetabolite conditioning. Preliminary studies using syngeneic mice transplanted with fresh marrow cells indicate that high levels of donor cell chimerism can be achieved with low-dose radiation or 5-fluorouracil-based conditioning regimens. Early data from experiments in which low-dose radiation-conditioned X-CGD recipients were transplanted with retrovirus-transduced X-CGD marrow cells show that gene-corrected neutrophils can be detected by NBT assay for NADPH oxidase activity reconstitution 4 months posttransplant, although these levels are much lower than the 50%-70% gene-corrected cell detected in lethally irradiated recipients. Transplantation of retrovirus-transduced marrow cells into 5-fluorouracil conditioned hosts is also being explored.
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PMID:Retroviral-mediated gene transfer and nonmyeloablative conditioning: studies in a murine X-linked chronic granulomatous disease model. 1246 30

Chronic granulomatous disease (CGD) is a fatal genetic disorder in which phagocytes fail to produce antimicrobial superoxide because of NADPH oxidase deficiency. Molecular defects in CYBB gene causing X-linked CGD are responsible for about 70% of all cases. This study was done to confirm genetic defects of CYBB gene in five Korean patients who were highly suggestive of having CGD by clinical history. We performed initial screening for five unrelated Korean patients using single strand conformation polymorphism (SSCP) and then selective sequencing for the regions involving the abnormal bands. Activated NBT tests revealed that all patients were X-linked. SSCP analysis for CYBB gene showed abnormal bands in all patients. The molecular defects of five patients were as follows: c.1663insT, c.1111-1G>T, c.39_40insG, c.927delC and c.434T>C mutation. This result will help the families with prenatal diagnosis or genetic counseling.
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PMID:Molecular analysis of X-linked chronic granulomatous disease in five unrelated Korean patients. 1508 94

Chronic granulomatous disease (CGD) is an inherited dysfunction of phagocytic cells secondary to a defect in the respiratory burst to kill catalase-positive microorganisms. This leads to recurrent life-threatening bacterial and fungal infections. We report a 1 year-10 month-old boy with X-linked CGD who was noted to have recurrent suppurative lymphadenitis since one and half month old. Failure to thrive, lymphadenitis and generalized skin lesions with multiple scar and dimples were found. Immunological data of patient, his mother and father were as follows: PMN phagocytosis (%): 98, 88, 92 (control, >80), PMN chemotaxis: 0.6, 1.0, 1.3 (control, >1.2), PMN bactericidal function test over a period of 2 hours (%): 28.1, 28.5, 84.8 (control, 82.1). PMN chemiluminescence (delta mV): 0.612, 364.1, 1131 (control, 614.1), H202 production (ug/mL): 1.6, 7.2, 16.8 (control, 14.1), NBT test: negative, mixed, positive (control, positive). His mother was a carrier. The patient expired with invasive salmonella infection before the availability of gamma-interferon prophylaxis.
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PMID:X-linked chronic granulomatous disease: report of one case. 1549 36

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

FHL1 mutations cause several clinically heterogeneous myopathies, including reducing body myopathy (RBM), scapuloperoneal myopathy (SPM) and X-linked myopathy with postural muscle atrophy (XMPMA). The molecular mechanisms underlying the pathogenesis of FHL1 myopathies are unknown. Protein aggregates, designated 'reducing bodies', that contain mutant FHL1 are detected in RBM muscle but not in several other FHL1 myopathies. Here, RBM, SPM and XMPMA FHL1 mutants were expressed in C2C12 cells and showed equivalent protein expression to wild-type FHL1. These mutants formed aggregates that were positive for the reducing body stain Menadione-NBT, analogous to RBM muscle aggregates. However, hypertrophic cardiomyopathy (HCM) and Emery-Dreifuss muscular dystrophy (EDMD) FHL1 mutants generally exhibited reduced expression. Wild-type FHL1 promotes myoblast differentiation; however, RBM, SPM and XMPMA mutations impaired differentiation, consistent with a loss of normal FHL1 function. Furthermore, SPM and XMPMA FHL1 mutants retarded myotube formation relative to vector control, consistent with a dominant-negative or toxic function. Mutant FHL1 myotube formation was partially rescued by expression of a constitutively active FHL1-binding partner, NFATc1. This is the first study to show that FHL1 mutations identified in several clinically distinct myopathies lead to similar protein aggregation and impair myotube formation, suggesting a common pathogenic mechanism despite heterogeneous clinical features.
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PMID:FHL1 mutants that cause clinically distinct human myopathies form protein aggregates and impair myoblast differentiation. 2463 12