Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.15.1 (ACE)
18,300 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neutral endopeptidase (NEP; E.C. 3.4.24.11) is a mammalian ectopeptidase identified as the common acute lymphoblastic leukemia antigen (CALLA or CD10). In order to investigate its cellular processing and its role in B lymphocyte differentiation, a fluorescent derivative of the mercapto NEP inhibitor thiorphan, N-[fluoresceinyl]-N'-[1-(6-(3-mercapto-2-benzyl-1-oxopropyl) amino-1-hexyl]thiocarbamide (FTI), has been synthesized. The fluorescent characteristics of fluorescein were conserved in FTI after linkage with the thiol NEP inhibitor. FTI inhibited NEP with an IC50 value of 10 nM and a good selectivity compared to that of aminopeptidase N (greater than 100 microM) and angiotensin converting enzyme (32 microM). The FTI probe was shown to detect membrane-bound NEP using photomicroscopy on cultured cells or flow cytometry techniques. Using NEP-expressing MDCK cells and episcopic fluorescence microscopy, a specific labeling was obtained with 100 nM FTI which was completely displaced by 10 microM HACBOGly, a specific and potent inhibitor of NEP. Therefore, FTI can be considered a suitable tool for following cellular NEP traffic. In flow cytometry, the fluorescent probe FTI, used at concentrations as low as 1 nM with Reh6 cells, could be very useful for detecting NEP/CALLA on lymphoid cells. In addition, the recognition of FTI is independent of tissues and species, a major advantage of inhibitors over monoclonal antibodies.
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PMID:Detection of neutral endopeptidase-24.11/CD10 by flow cytometry and photomicroscopy using a new fluorescent inhibitor. 135 7

Primary biliary cirrhosis (PBC) is a chronic autoimmune liver disease that includes the presence of lymphoid infiltrates in portal tracts, high titer autoantibodies against pyruvate dehydrogenase-E2 (PDH-E2) and branched chain ketoacid dehydrogenase-E2 (BCKD-E2), and biliary tract destruction. The mechanism by which the autoimmune response is induced, the specificity of damage to the biliary epithelium, and the role of T cells in PBC are still unknown. To address these issues, we have taken advantage of a mouse mAb, coined C355.1, and studied its reactivity against a panel of liver tissue from normal subjects as well as a panel of liver specimens from patients with PBC, progressive sclerosing cholangitis, and chronic active hepatitis (CAH). C355.1, much like human autoantibodies to PDH-E2, reacts exclusively by immunoblotting with PDH-E2, binds to the inner lipoyl domain of the protein, and inhibits PDH-E2 activity in vitro. In addition, we have also attempted to develop cloned T cell lines that react with PDH-E2 and/or BCKD-E2 using liver biopsies from patients with PBC, compared with CAH. Although monoclonal C355.1 produced typical mitochondrial fluorescence on sections of normal liver, pancreas, lung, heart, thyroid, and kidney, it produced a distinct and intense reactivity when used to stain the bile ducts of patients with PBC. Nine of 13 PBC liver biopsies studied herein contained bile ducts on light microscopy, all of which reacted intensely at a 1:100 culture supernatant dilution of monoclonal C355.1. In contrast, although bile ducts of liver specimens from normals, CAH, and progressive sclerosing cholangitis also reacted with C355.1, such reactivity was exclusively mitochondrial and readily detectable only at a dilution of 1:2. More importantly, we generated CD4+, CD8-, alpha beta TCR+ cloned T cell lines from patients with PBC, but not from CAH, that produced IL-2 specifically in response to PDH-E2 or BCKD-E2.
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PMID:Evidence for the targeting by 2-oxo-dehydrogenase enzymes in the T cell response of primary biliary cirrhosis. 198 55

Taking advantage of the recently demonstrated identity of common acute lymphoblastic leukemia antigen (CALLA) and neutral endopeptidase EC.24.11 (NEP) the presence of this ectoenzyme on lymphoid cells has been reassessed using highly sensitive assays (cleavage of [3H]-D-Ala2-leucine-enkephalin and binding of the inhibitor [3H]HACBO-Gly. NEP activity was found not only on already classified CALLA + ve cells but also on numerous cells (including mature B and polyclonal T cells) previously considered as CALLA-ve. This suggests that CALLA/NEP is expressed all along the differentiation pathway in B and T cell lineage. Moreover substantial ACE-like activity was also detected in three tested cells, all of the pre-B phenotype. The availability of specific inhibitors for these enzymes should help clarify their role in cell-differentiation.
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PMID:Neutral endopeptidase 24.11 and angiotensin converting enzyme like activity in CALLA positive and CALLA negative lymphoid cells. 254 97

These perspectives from the first International Symposium on Primary Biliary Cirrhosis review recent advances and single out some areas for further enquiry. The latter include frequency and type of associated autoimmune diseases, the existence of clinical subsets of PBC, immunohistochemical analysis of lymphoid infiltrates in the liver, effects of immunosuppressive and other treatment regimens, and models for predicting the optimal time for liver transplantation. The M2 autoantigens have been identified as mitochondrial 2-oxo-acid dehydrogenase enzymes. These include pyruvate dehydrogenase (70-74 kd antigen) and branched chain 2-oxo-acid dehydrogenase and 2-oxo-acid glutaric dehydrogenase (45-52 kd antigens). Each of these enzymes has three subunits, E1 to E3. For PDH, an autoepitope has been identified as a decapeptide containing the attachment site of lipoic acid, an essential cofactor for enzyme activity. Current questions include the degree to which antibodies to PDH, and related enzymes, account for the mitochondrial reactivity defined by immunofluorescence or other procedures, the cell-surface expression of M2 autoantigens, and the significance of the occurrence of nonmitochondrial (such as centromeric) autoantibodies in PBC. The unknown T lymphocyte contribution to the autoimmune response in PBC may involve inducer and effector components. A postulated T-cell autoepitope may be presented, in association with MHC class I or class II molecules, on the surface of biliary epithelial cells. T cell lines from PBC livers removed during transplantation could provide data on the T-lymphocyte contribution to the pathogenesis of PBC.
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PMID:Primary biliary cirrhosis: current knowledge, perspectives, and future directions. 265 6

Of some 750 sarcoidosis patients, 27 were found to have involvement of their nasal mucosa. Most had multisystem disease, which was usually chronic. Nasal stuffiness or blockage and crusting were the major symptoms, and were usually present at the first presentation with sarcoidosis. The larynx was involved in five cases. The Kveim test was positive in twelve of the fourteen patients in whom it was performed, serum angiotensin converting enzyme was frequently elevated and sinus radiographs were often abnormal. Topical medication improved symptoms in some patients, but the majority required systemic corticosteroids. It was possible to withdraw medication completely after seven years in only one patient. Relapse was encountered during reduction of dosage in other patients. Random biopsy of macroscopically normal nasal mucosa did not yield histological support for a diagnosis of sarcoidosis in twelve out of thirteen patients, but upper respiratory tract lymphoid tissue may contain granulomas in patients with sarcoidosis.
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PMID:Upper respiratory tract involvement in sarcoidosis and its management. 338 80

Endothelial cells from mouse peripheral lymph nodes were immortalized by cationic liposome-mediated transfection using a plasmid construct containing both the gene coding for the large T antigen of simian virus 40 and a geneticin resistance gene suitable for selection. A cell line (HECa10) was isolated on the basis of its capacity to specifically bind fucoside carrying glycoconjugates; these cells present the main characteristics of endothelial cells: production of angiotensin converting enzyme and of factor VIII-related antigen. Upon stimulation, they express E-selectin which binds oligosaccharides containing the Lewisx determinant (Fuc alpha 3[Gal beta 4 GlcNAc beta 3Gal beta) and the MECA 79 addressin which is characteristic for the peripheral lymph node high endothelium and is a L-selectin ligand. HECa10 cells, as well as peripheral lymph node high endothelial cells in primary culture, express a second fucoside binding protein which differs from E-selectin. Indeed, this new fucoside-binding protein is constitutively expressed on unstimulated cells while E-selectin is not. Furthermore, HECa10 cells mediate selective lymphoid cell adhesion in a selectin/addressin-dependent mechanism, mainly inhibited by MECA 79 antibody and, in a fucose-binding lectin-dependent manner, mainly inhibited by the specific neoglycoprotein.
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PMID:A SV-40 immortalized murine endothelial cell line from peripheral lymph node high endothelium expresses a new alpha-L-fucose binding protein. 751 29

Two cases of type C chronic hepatitis with the presence of epitheloid granulomas were reported. Case 1 was a 44-year-old man who presented with a moderate increase in serum ALT and positive anti-HCV. Histological examination of percutaneous liver biopsy specimens showed dense portal inflammation with piecemeal necrosis. Lobular inflammation was present mederately and a large well-organized epitheloid granuloma was found within a liver lobule. Case 2 was a 55-year-old woman, who was presented because of a slight increase in serum ALT and positive anti-HCV. Histologically, liver biopsy specimens showed lymphoid aggregates in the portal area and slight piecemeal necrosis. Moderate steatosis were noted and an epitheloid granuloma was present in the hepatic lobule. Acid-fast stains were negative for both cases and serum ACE and lysozyme were within normal range. These granulomas were composed of epitheloid cells surrounded by lymphocytes. They were not present within the portal tracts, but were found in the hepatic lobule. The incidence of the appearance of epitheloid granuloma in liver biopsy specimens of type C chronic hepatitis was 2 out of 273 cases (0.73%). The role of HCV infection in the genesis of epitheloid granulomatosis is of much interest and should be investigated.
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PMID:Epitheloid granuloma formation in type C chronic hepatitis: report of two cases. 759 May 82

A 48-year-old woman developed granulomatous slack skin (GSS), one of the special forms of cutaneous T-cell lymphoma. The lesional skin slack with an atrophic, poikilodermic surface and granulomatous induration. Histopathological findings included epidermotropism, diffuse lymphoid cell infiltration and foreign body giant cells as well as granulomatous reactions from superficial to deep dermis, including part the subcutis. The diagnosis was established by positive results for rearrangement of the T-cell receptor gene. The therapeutic possibilities, especially with corticosteroids and monitoring the disease course by following serum angiotensin converting enzyme activity are discussed.
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PMID:[Granulomatous slack skin]. 952 91

A quantitative competitive RT-PCR method was developed in order to measure IL-1beta, IL-4, IL-12, IFNgamma, TNFalpha and G(3)PDH mRNA from samples of ovine tissue such as lymph node or spleen. The main advantage of the method relies on the use, for each target sequence, of an internal competitor construct similar to the relevant target, but 4-bp different in size. This competitive strategy is validated by the equivalence of the amplification process, observed separately between competitor DNA and target DNA species. Furthermore, the copy number of each cytokine cDNA is normalized to a fixed copy number of G(3)PDH cDNA. The cDNA level of this constitutive gene was effectively shown to remain constant whatever the tissue studied and independently of the experimental conditions used. The accurate and reproducible data obtained permit the application of this quantitative RT-PCR method to measure the sheep cytokine response to Salmonella infection. Early induction of IFNgamma mRNA was observed in the draining lymph node 1 day after infection. At the same time, a strong increase of IL-1beta mRNA was observed in local and systemic lymphoid organs, suggesting the initiation of the inflammatory response. Finally, the overall results demonstrate the efficiency of the method and its suitability for further studies of the immune response in the ovine species.
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PMID:Quantification of ovine cytokine gene expression by a competitive RT-PCR method. 1138 71

A 77-year-old man was admitted to a hospital because of a left cervical tumor. He was initially diagnosed as having non-Hodgkin lymphoma, diffuse large cell type, Ann Arbor stage IV, and transferred to our hospital for chemotherapy. Flow cytometric analysis of the left axillary lymph node cells derived from a biopsy specimen showed that in addition to lymphoid surface markers (CD5, 7, 21), myeloid surface markers (CD11b, 33, 34) were also positive. The diagnosis of malignant lymphoma was therefore confirmed. The patient, was treated with THP-COP therapy, which proved very effective. Thereafter, a biopsy specimen was found to be positive for MT1 (CD43) staining but negative for myeloperoxidase and chloroacetate esterase staining on immunohistochemistry. Furthermore, no rearrangement of the IgH JH, TCR C beta 1 or TCR J gamma gene was detected by Southern blot analysis. On basis of these findings and the previous results of flow cytometry, we changed the diagnosis from malignant lymphoma to granulocytic sarcoma. THP-COP therapy was continued, and complete remission was achieved. Two months later, however, the patient developed acute myelocytic leukemia (AML M1) and received DCP therapy, but he died of pneumonia.
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PMID:[Granulocytic sarcoma developing in lymph nodes]. 1209 91


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