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

---

Query: EC:3.1.1.7 (acetylcholinesterase)
28,390 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

FACS analysis together with PIPLC treatment was applied to PI-anchoring antigens such as DAF (decay-accerelating factor, CD55), 1F5 antigen (CD59), CD14 and CD16 on the cell surfaces of blood cells from a normal adult and a male patient with paroxysmal nocturnal hemoglubinuria (PNH). Through the extensive analysis, this patient proved to be completely defective in 1F5 antigen, a newly found complement-regulatory protein, on all the blood cells tested. In normal blood cells such as lymphocytes, monocytes and granulocytes, 1F5 antigen was expressed as one of PI-anchoring proteins. In contrast to most of PNH patients, this patient reserved DAF, CD14 and CD16 at normal levels in his erythrocytes, monocytes and granulocytes. Also, there were no significant differences between the normal adult and the patient in the activities of erythrocyte acetylcholinesterase and granulocyte alkaline phosphatase which were also known to be PI-anchoring enzymes. Thus, deficiency of 1F5 antigen must be deeply related to the clinical symptoms of PNH in this patient.
...
PMID:Analysis of PI (phosphatidylinositol)-anchoring antigens in a patient of paroxysmal nocturnal hemoglobinuria (PNH) reveals deficiency of 1F5 antigen (CD59), a new complement-regulatory factor. 168 70

The sensitivity to lysis by complement of the erythrocytes of 56 patients with paroxysmal nocturnal haemoglobinuria (PNH) was compared to the membrane expression of decay accelerating factor (DAF, CD55), membrane inhibitor of reactive lysis (MIRL, CD59) and acetylcholinesterase (AChE). Most patients (36/50 72% in whom the analysis could be made) appeared to have erythrocytes of intermediate sensitivity to complement in the blood. These cells appeared as a discrete population of cells (PNH II cells), as a 'tail' of cells slightly less sensitive than the predominant PNH III cells (previously called PNH IIIb cells), or as a continuous spectrum of cells sensitive to complement. The PNH III cells totally lacked all three proteins (DAF, MIRL, AChE) by flow cytometric analysis whereas PNH I cells appeared to have normal or nearly normal amounts of each. The cells of intermediate sensitivity (PNH II) had coordinately decreased expression of all three proteins; the level of expression of DAF and MIRL paralleled the sensitivity of the cells to the haemolytic action of complement.
...
PMID:The erythrocytes in paroxysmal nocturnal haemoglobinuria of intermediate sensitivity to complement lysis. 171 64

We have used a panel of well-characterized monoclonal antibodies (MoAbs) to examine the blood cells of a patient with a novel form of congenital dyserythropoietic anemia (CDA) characterized by intra-erythroblastic and intra-erythrocytic membranous inclusions. Twelve antibodies defining three nonoverlapping epitope groups on the extracellular domain of CD44 all failed to react with the red blood cells (RBCs) of the patient. A rabbit antibody to the cytoplasmic domain of CD44 from normal RBCs failed to react with the patient's RBC ghosts. In contrast, the patient's lymphocytes, granulocytes, and monocytes showed apparently normal CD44 expression. Bone marrow preparations stained with CD44 antibodies and visualized with 125I antimouse Ig (F(ab')2) followed by autoradiography showed positive staining of lymphocytes and myeloid cells but not of most orthotolidine-positive erythroblasts. The patient's RBCs also gave weaker than normal reactions with MoAbs of anti-LWab specificity while MoAbs to glycophorins A, B, and C, Rh polypeptides, CD47, CD55, CD58, CD59, acetylcholinesterase, and Lutheran and Kell glycoproteins all gave normal reactions. Agglutination tests with human blood grouping sera demonstrated that the RBCs of the patient have the unique phenotype In(a-b-), Co(a-b-) and that they also lack the high incidence RBC antigen AnWj. The phenotype In(a-b-) would be expected because these antigens are known to be expressed on CD44. There is also some evidence associating the AnWj antigen with CD44. However, the CO blood group locus is on chromosome 7p whereas that for CD44 is on chromosome 11p. Quantitative binding assays using 125I-labeled Fab fragments of CD44 antibodies did not show any evidence for reduced levels of CD44 on RBCs from the parents of the patient or from her unaffected sister. The parents and sister had the common Colton blood group phenotype [Co(a+b-)]. Neither deficiency of CD44 nor absence of Colton antigens are general features of CDA because erythrocytes from patients with CDA I, CDA II, CDA III, and two other unclassified CDAs had normal expression of CD44 and normal Colton blood group phenotypes. Further analysis of the defect(s) present in the patient's erythroid cells may provide useful information regarding membrane assembly and the regulation of differentiation in normal erythroid cells.
...
PMID:A novel form of congenital dyserythropoietic anemia associated with deficiency of erythroid CD44 and a unique blood group phenotype [In(a-b-), Co(a-b-)]. 750 39

A 55-year-old man was admitted to our department because of shortness of breath and pancytopenia on March 27, 1992. On admission, palpebral conjuctiva were anemic. Laboratory findings showed pancytopenia, a reticulocyte count of 44,835/microliters, hemosiderinuria, LDH of 710 IU/l, haptoglobin of 6 mg/dl, NAP score of 301, red cell acetylcholinesterase of 1.5 U, negative Ham's test and negative sugar water test. Bone marrow was hypoplastic (2.4 x 10(4)/microliters). The erythrocytes of this patient showed complement-sensitive cells by the complement lysis sensitivity test, and a negative population consisting of double negative erythrocytes by flow cytometric two-color analysis using monoclonal antibodies to CD55 and CD59. A diagnosis of PNH with hypoplastic bone marrow was thus made. Therefore, flow cytometric two-color analysis appears to be superior to the standard tests currently used.
...
PMID:[Negative Ham's test and sugar water test on admission in paroxysmal nocturnal hemoglobinuria]. 796 61

Two affected individuals of the Swedish family with CDA, type III, in which the disease is transmitted as an autosomal dominant character, were studied. Both cases displayed features hitherto undescribed in this family but described in patients with CDA, type III, in whom the inheritance may have been as an autosomal recessive character. Such features were: (a) haemosiderinuria, (b) grossly disorganised erythroblast nuclei, (c) differences in the ultrastructural appearances of individual nuclei within the same multinucleate erythroblast and (d) intraerythroblastic inclusions resembling precipitated globin chains. In both cases the giant mononucleate erythroblasts and the multinucleate erythroblasts had total DNA contents up to 28c (1c = haploid DNA content) and 48c respectively, and some DNA synthesising bi- and multinucleate erythroblasts contained one or more nuclei which were unlabelled with 3H-thymidine. These findings are similar to those in patients with the autosomal recessive type of disease. Thus no major phenotypic differences are yet apparent between cases of CDA, type III, with different patterns of inheritance. Analysis of the surface erythrocyte proteins of the 2 Swedish CDA, type III, patients with monoclonal antibodies recognising Band 3, glycophorins A, B, C and D, Rh, CD44, CD47, CD55, CD58, CD59, Lutheran, Kell, LW and acetylcholinesterase did not reveal any gross abnormality of expression of these proteins. A slightly altered expression of blood group antigens A and H was revealed by the lectins Dolichos biflorus and Ulex europaeus and the Mr of Band 3 as judged by SDS polyacrylamide gel electrophoresis was also slightly reduced, suggesting that there may be minor alterations in the degree of N-glycosylation of some red cell membrane constituents.
...
PMID:Observations on two members of the Swedish family with congenital dyserythropoietic anaemia, type III. 850 Jun 3

Human erythrocyte cell surface molecules that are attached to the cell membrane by glycosyl-phosphatidylinositol (GPI) anchors include the complement regulatory proteins decay accelerating factor (DAF, CD55) and membrane inhibitor of reactive lysis (MIRL, CD59), as well as the proteins that bear the Cartwright, Dombrock, and JMH blood group antigens. The acquired hematopoietic stem cell disorder paroxysmal nocturnal hemoglobinuria (PNH) results from the absence or marked deficiency in expression of GPI-anchored proteins in affected hematopoietic cells. PNH usually if not always results from a somatic mutation of an X-linked gene called PIG-A; the product of the PIG-A gene is a glycosyl transferase necessary for construction of the GPI anchor. DAF is a ubiquitously expressed protein present in many tissues, including gastrointestinal epithelia, corneal epithelia, and serosa of urinary and reproductive organs. DAF is a 70 kD glycoprotein containing complement regulatory short consensus repeats (SCRs); its gene is located in the regulation of complement activation (RCA) gene cluster on chromosome 1 and is about 40 kb in size. The Cromer blood group antigens, which reside on DAF, include 10 currently defined antigens, of which seven are of high incidence. The molecular basis of the Cr (a-) phenotype has been determined to be a single base pair substitution in DAF SCR4 (G-->C, leading to an ala193 to pro amino acid substitution). The Tc alpha antigen appears to be determined by the amino acid sequence of SCR1, with the Tc (a-b+) phenotype arising from a base pair substitution of G55-->T, leading to an arg18 to leu amino acid substitution. The null phenotype for Cromer antigens occurs when DAF is completely absent; only one example has been completely studied on the molecular level. That individual is homozygous for a point mutation in SCR1 (G314-->A) that creates a stop codon (TGA) in place of one normally encoding trp53 (TGG) and thus prevents further translation of the mRNA. The Dr(a-) phenotype expresses reduced quantities of DAF (approximately 40% of normal levels), as well as a polymorphism of DAF. Lack of the Dr alpha antigen has been proved to result from a single point mutation in SCR3 (C-->T in codon 165) that leads to a single amino acid substitution (ser-->leu). The Cartwright (Yt) antigens reside on acetylcholinesterase (AChE). In erythroid cells, a small exon that encodes the signal for attachment of the GPI anchor is retained in a tissue-specific process.(ABSTRACT TRUNCATED AT 400 WORDS)
...
PMID:Glycosyl phosphatidylinositol-linked blood group antigens and paroxysmal nocturnal hemoglobinuria. 854 26

Human erythrocyte CD59 contains N- and O-glycans and a glycosylphosphatidylinositol (GPI) anchor, all of which have been analyzed in this study. The anchor consists principally of the minimum core glycan sequence Manalpha1-2Manalpha1-6Manalpha1-4GlcN-linked to a phosphatidylinositol moiety with the structure sn-1-O-alkyl(C18:0 and C18:1)-2-O-acyl(C20:4)glycerol-3-phospho-1-(2-O-palmitoyl(C16:0))myo- inositol. This structure is essentially identical to that of human erythrocyte cholinesterase (Deeg, M. A., Humphrey, D. R., Yang, S. H. , Ferguson, T. R., Reinhold, V. N., and Rosenberry, T. L. (1992) J. Biol. Chem. 267, 18573-18580). This first comparison of GPI anchors from different proteins expressed in the same tissue suggests that human reticulocytes produce only one type of anchor structure. The N- and O-glycans were sequenced using a novel approach involving digestion of the total glycan pool with multiple enzyme arrays. The N-glycan pool contained families of bi-antennary complex-type structures with and without lactosamine extensions and outer arm fucose residues. The predominant O-glycans were NeuNAcalpha2-3Galbeta1-3GalNAc and Galbeta1-3[NeuNAcalpha2-3]GalNAc. Inspection of a molecular model of CD59, based on the NMR solution structure of the extracellular domain and the structural data from this study, suggested several roles for the glycans, including spacing and orienting CD59 on the cell surface and protecting the molecule from proteases. This work completes the initial structural analysis of CD59, providing the most complete view of any cell surface glycoprotein studied to date.
...
PMID:The glycosylation of the complement regulatory protein, human erythrocyte CD59. 905 19

Systemic injection of antibodies against acetylcholinesterase (AChE) induces complement-mediated destruction of preganglionic nerve terminals in paravertebral sympathetic ganglia, but spares other AChE-rich structures, such as nerve terminals in prevertebral sympathetic ganglia, parasympathetic ganglia, and the neuromuscular junction. This pattern of differing sensitivity to "AChE immunolesion" might be explained by a differing expression of proteins that serve to protect host cells from complement activation. Two major complement regulatory proteins in rats are Crry, which interferes with the assembly of C3 convertase, and CD59, which blocks formation of the terminal cytolytic membrane attack complex. The present study used immunohistochemistry to demonstrate an inverse relation between levels of CD59 and Crry expression and sensitivity to AChE immunolesion in several AChE-rich targets. Thus, the most sensitive structures, i.e., preganglionic nerve terminals in the adrenal gland and superior cervical ganglion (SCG), expressed undetectable levels of CD59 and Crry immunoreactivities. By contrast, AChE-rich, but antibody-resistant, cholinergic nerve terminals in the inferior mesenteric ganglia (IMG) and diaphragm muscle expressed significant amounts of CD59 and Crry. Such expression was functionally important because, after membrane-anchored CD59 was removed from explanted IMG with phosphatidylinositol phospholipase C, exposure to AChE antibody and complement caused greater immunolesion. It was concluded that differential expression of regulatory proteins in different parts of the nervous system influences regional vulnerability to complement mediated damage.
...
PMID:Complement regulatory proteins and selective vulnerability of neurons to lysis on exposure to acetylcholinesterase antibody. 1128 54

---