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)

Selectivity for the carboxy-terminus of angiotensin II (Ang II) and the high affinity of antibodies are prerequisites for clinical assays that evaluate Ang II in the presence of Ang I. A high-affinity monoclonal antibody (Kd = 7.1 X 10(-11) mol/l) was produced and used for the measurement of plasma Ang II. C3H mice were immunized with Ang II coupled by its carboxy-terminus to thyroglobulin. Somatic cell fusion between spleen cells and SP 2/0 myeloma cells, repeated subcloning and re-injection into mice yielded ascites containing sufficient antibody at a 2 X 10(7)-fold dilution. Radioassay standard curves show 50% tracer displacement when 32 fmol unlabelled Ang II is added and 2 fmol Ang II can be detected. Cross-reactivities, taking the reactivity with Ang II as 1.00 are: Ang I 0.003, Ang (1-7) 0.00001, Ang III 1.05, Ang(3-8) 0.88 and Ang(4-8) 0.75. Fast extraction of angiotensin from 2 ml plasma by reversible adsorption to phenylsilylsilica (Bondelut PH) provides recoveries of 96-102%. During angiotensin converting enzyme inhibition with 25 mg intravenous captopril, plasma immunoreactive Ang II decreased in supine normal volunteers from 8.6 +/- 3.6 to 4.5 +/- 3.4 fmol/ml (P less than 0.01, n = 8). It thus appears that plasma immunoreactive Ang II can now be measured after a simple extraction procedure by using monoclonal antibodies.
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PMID:Angiotensin II measurement with high-affinity monoclonal antibodies. 324 Dec 30

A 72-year-old man experienced a postoperative acute renal failure (ARF) from a nonsteroidal anti-inflammatory drug (NSAID) and an angiotensin converting enzyme inhibitor (ACEI) intake and promoted by an unrecognized myeloma, peroperative hypotension and hormonal response to surgical stress. This drug combination can result in ARF through a fall of glomerular filtration by combined renal blood flow changes: NSAID inhibit vasodilation by renal prostaglandins, and the vasoconstrictor effect on the efferent arteriole is inhibited by the ACEI. Nephrotoxicity during the simultaneous use of ACEI and NSAID is increased by other risk factors of renal insufficiency such as ageing, preexisting renal disease and hypovolaemia. In these cases, a preventive therapy should be considered.
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PMID:[Non-steroidal anti-inflammatory agent and angiotensin converting enzyme inhibitor: a dangerous combination during postoperative period]. 968 97

Serum screening for homogeneous immunoglobulins (H-Ig) was done on 149 apparently healthy Ghanaians (aged 17-95 years) and 73 sick subjects who presented at the Korle-Bu Teaching Hospital from October 1999 to September 2000. Sera were screened by agarose gel electrophoresis and those with equivocal results were confirmed by immunoelectrophoresis. Immunoglobulin classes (IgG, IgA and IgM) and Bence Jones proteinuria were measured and determined by single radial immunodiffusion method and heating respectively. Total protein, albumin, calcium, uric acid, urea and creatinine were estimated on ACE chemistry autoanalyser. The laboratory profile of 5 Ghanaians with a picture of multiple myeloma and one with monoclonal gammopathy of undetermined significance drawn from the sick subjects (6 of 73) are presented. None of the 149 healthy subjects studied in three age groups (17-40; 41-64 and dollar 65 years) had H-Ig, and their serum IgG, IgA, IgM, urea, creatinine, uric acid, calcium, total protein and albumin levels were within the normal range. H-Ig were present in sera of 6 out of the 73 sick subjects (8.2%); 5 of them (4 males, 1 female) presented a picture of multiple myeloma. Three of these 5 patients had IgG, and the others IgA paraproteinaemia. All 5 patients had immunoparesis which was absent in the 6th patient (a male) who also had IgA paraproteinaemia (< 10 g/L), active bone marrow with < 2% mature plasma cells and no renal involvement. Results of bone marrow examination supported a diagnosis of multiple myeloma in the 3 patients with IgG paraproteinaemia, but were not available for the other two. Bence-Jones proteinuria was found in 2 (both with IgG paraproteinaemia) of 4 patients (50%) available for testing. Renal involvement was indicated in the 5 patients with a picture of multiple myeloma as urea and creatinine levels were significantly raised.
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PMID:Homogeneous immunoglobulins in Ghanaians living in Accra, Ghana. 1597 37

Sotatercept (ACE-011), under development by Acceleron Pharma Inc in collaboration with Celgene Corp, is a chimeric protein containing the extracellular domain of the activin receptor 2A (ACVR2A) fused to the Fc domain of human IgG1. Sotatercept contains the binding site of ACVR2A and interferes with downstream signaling cascades, in particular the SMAD pathway, by sequestering activin. The murine counterpart of sotatercept, referred to as RAP-011, has been extensively evaluated in preclinical studies, in particular in models of cancer- and osteoporosis-related bone loss, and the developing companies envisage that sotatercept may also have potential for the treatment of cancer and cancer-related bone loss. In a phase I clinical trial in postmenopausal females, sotatercept increased hematocrit levels, and, in a phase II trial in patients with multiple myeloma, a trend toward improvement in osteolytic lesions as well as antitumor activity was observed. At the time of publication, phase II trials in patients with anemia were ongoing. Future clinical development will rely on an evaluation of the benefits and complications of sotatercept administration, focusing in particular on suppression of ovarian function and increases in hematocrit levels without a consequent risk of hypertension and thrombosis.
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PMID:Sotatercept, a soluble activin receptor type 2A IgG-Fc fusion protein for the treatment of anemia and bone loss. 2088 91

We discuss a case of a 61-year-old woman who presented with substernal chest pain. She was found to have elevated calcium levels, anemia, and acute kidney injury. The hypercalcemia persisted despite therapy with fluids and bisphosphonates. She was found to have nonparathyroid hormone (PTH) mediated hypercalcemia. The chest X-ray did not reveal any pathology. Our Initial impression was likely underlying hematologic malignancy such as lymphoma or multiple myeloma. A bone marrow biopsy was performed that revealed nonnecrotizing granulomatous inflammation. Further workup revealed elevated vitamin 1,25 dihydroxy level, beta-two microglobulin level, and ACE levels. Noncontrast computed tomography (CT) scan of chest showed bilateral apical bronchiectasis, but did not show any lymphadenopathy or evidence of malignancy. Subsequently, a fiber optic bronchoscopy with transbronchial biopsy showed nonnecrotizing granulomatous inflammation consistent with sarcoidosis. After initiating glucocorticoid therapy, the patient's hypercalcemia improved and her kidney function returned to baseline.
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PMID:Hypercalcemia, Anemia, and Acute Kidney Injury: A Rare Presentation of Sarcoidosis. 2619 27

Introduction: The insertion (I allele) deletion (D allele) polymorphism of ACE gene (rs4646994) may influence the etiopathogenesis of multiple myeloma (MM). ACE gene is expressed in bone marrow cells and encodes angiotensin converting enzyme (ACE). It converts angiotensin I to active peptide angiotensin II, which stimulates proliferation of hematopoietic stem cells. This suggests possible association of ACE I/D gene polymorphism with MM. The aim of our study was to check possible impact of this polymorphism on risk of development and outcome of MM, as well as, sensitivity to bortezomib in cell cultures derived from MM patients. Objects and Methods: Genomic DNA from 98 newly diagnosed MM patients and 100 healthy blood donors were analyzed by PCR method. Chromosomal aberrations were detected by use of cIg-FISH. In a subgroup of 40 MM patients nucleated bone marrow cells were treated with bortezomib in vitro. Results: The Hardy-Weinberg equilibrium test showed that genotypic frequencies diverged significantly from the equilibrium. The differences between I and D allele frequencies in control and study population were significant (p = 0.046). We observed the association between DD genotype and more than 2-fold risk of MM - OR = 2.69; p < 0.0001. We did not detect any significant differences among studied genotypes regarding clinical and laboratory parameters. Moreover, we did not observe the association between survival of MM patients and I/D genotypes. Bortezomib increased number of apoptotic and necrotic cells, but the only statistically significant differences were observed in the number of viable cells at 1 nM between ID and DD genotypes (p = 0.026). Conclusion: Presented results confirmed the significant relationship between ACE (I/D) polymorphism and risk of MM development. We did not observe the association of ACE I/D polymorphism with disease outcome and bortezomib in vitro sensitivity.
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PMID:ACE Insertion/Deletion Polymorphism (rs4646994) Is Associated With the Increased Risk of Multiple Myeloma. 3078 88