Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0432222 (SEM)
 47,337 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We describe the development of a new ELISA for the detection of neural endopeptidase 3.4.24.11 (NEP). Neutral endopeptidase 3.4.24.11 was determined in preparations of human granulocytes, mononuclear cells (MNC), and in serum. Human recombinant NEP was used as reference. Specificity of the mAbs was tested using APAAP, FACS analysis, and Western blot analysis. Lysis of the blood cells was performed by incubating the cells with 0.4% Tween-20 and repeated freezing cycles. The minimal detectable dose for recombinant NEP was 15 pg/ml. The recovery was 94 +/- 9%. The NEP was detectable in 15 out of 20 serum samples of 20 volunteers (mean +/- SEM, 245 +/- 88 pg/ml, n = 20)) and in all granulocyte preparations (1176 +/- 138 pg/10(7) cells, n = 20)). The results were reproducible among replicates (CV = 3 +/- 1%, n = 40), dilutions (CV = 8 +/- 2%, n = 5), and assays (CV = 12 +/- 4%, n = 5). With this new ELISA, a simple and reproducible method for the measurement of NEP 3.4.24.11 is described.
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PMID:ELISA for the neuropeptide degrading endopeptidase 3.4.24.11 in human serum and leukocytes. 752 44

Neutral endopeptidase (NEP) is found in many tissues in man, including the lung. Metabolism by NEP is one of the main mechanisms for the clearance of atrial natriuretic peptide (ANP), a hormone that causes bronchodilation and reduces nonspecific bronchial reactivity in man. Candoxatril, an oral NEP inhibitor has been shown to elevate circulating ANP levels. We have sought to determine whether the administration of candoxatril will alter bronchomotor tone (forced expiratory volume in one second (FEV1)) and histamine reactivity. Ten male asthmatic patients with stable asthma were enrolled (mean (SD) age 32 (10) yrs; FEV1 92 (11)% predicted) in a randomized, double-blind, placebo-controlled study. On each study day, after baseline spirometry, patients received 200 mg of candoxatril or placebo. Spirometry was repeated at half hourly intervals. After 2 h a histamine inhalation test was performed. There was no significant difference in FEV1 values at baseline or at 2 h post-dosing between active and placebo study days, with mean (SEM) FEV1 at baseline and 2 h of 3.71 (0.29) l and 3.85 (0.29) l on the placebo day, and 3.89 (0.27) l and 4.05 (0.82) l on the active day, respectively. The geometric mean (range) provocative concentration of histamine producing a 20% fall in FEV1 (PC20) on the placebo day and active day did not differ significantly, being 1.17 (0.25-25.8) and 0.93 (0.13-32) mg.ml-1, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:No effect of the oral neutral endopeptidase inhibitor candoxatril, on bronchomotor tone and histamine reactivity in asthma. 792 77

Neutral endopeptidase (EC 3.4.24.11; NEP), originally isolated from renal tubular brush border, is a cell surface peptidase identical to the CD10 antigen (or CALLA; common acute lymphoblastic leukemia antigen) in lymphoid cells. We studied the serum NEP levels daily after transplantation (Tx) in 19 renal allograft recipients. The NEP activity was determined with a two-step enzymatic assay utilizing a fluorogenic substrate (Suc-Ala-Ala-Phe-AMC; see text) and related to clinical signs of graft rejection, to signs of immunoactivation in transplant fine-needle aspiration biopsy (FNAB) specimens, to renal function, and to serum levels of C-reactive protein. The serum NEP levels remained normal (peak level 10.3 +/- 1.8 micrograms/l on days 6-9 after Tx, initial level after Tx 7.3 +/- 1.4 micrograms/1 on day 2; mean values +/- SEM) in patients who neither showed clinical signs of rejection nor had findings of immunoactivation in FNAB samples. On the contrary, the serum NEP levels rose clearly in patients developing acute rejection verified clinically and in FNAB samples (peak value 90.4 +/- 18.7 micrograms/l on days 6-9 post-Tx; p < 0.001 compared with patients without sings of immunoactivation) and even in patients having immunoactivation in FNAB without clinical evidence of rejection (108.2 +/- 22.4 micrograms/l, p < 0.001). Serum NEP peak appeared 2-3 days before clinical diagnosis of rejection and a positive findings in FNAB samples. Serum NEP increments did not correlate with changes in serum creatinine, delayed onset of renal excretory function, blood leukocyte count, C-reactive protein level, or infections. Thus, the serum NEP activity was shown to increase after renal allotransplantation associated with early phases of immunoactivation and development of acute graft rejection. Because of the limited number of patients studied, the clinical implications of these preliminary observations for kidney transplant monitoring clearly need confirmation in larger studies.
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PMID:Increased serum neutral endopeptidase activity in acute renal allograft rejection. 873 78

Neutral endopeptidase (NEP) is described in airways as the major degrading enzyme of tachykinins such as neurokinin A (NKA) and substance P (SP). Due to its localization and mode of action NEP may play a role in the pathophysiology of bronchial reactivity (BR) especially under the aspect of neurogenic inflammation. Serum NEP concentrations were measured by ELISA to investigate if there is a correlation between serum NEP and the degree of bronchial reactivity expressed by PC20-FEV1 histamine(.). PC20-FEV1 histamine was determined in 31 asthmatic patients [age 31.9+/-1.3 years (mean+/-SEM) FEV1=92.1+/-2.4% (mean+/-SEM) 16 females/15 males]. Prior to the histamine challenge blood samples were obtained and stored at -70 degrees C until determination using ELISA. A significant correlation between serum NEP and the PC20-FEV1 (n=31, r=0.49, P<0.01) was found. The results suggest that serum NEP is modulating neuropeptide-induced effects in the pathophysiology of airway responsiveness.
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PMID:Correlation between neutral endopetidase (NEP) 3.4.24.11 in serum and the degree of the bronchial hyperreactivity. 1116 54