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

In the last two years the authors have noted the cases of five patients with pulmonary tuberculosis to which intermittent treatment with Rifampicin was administered (twice weekly, 600-900 mg/day), in association with Ethambutol. Between 2 and 6 months after the treatment was started, 24-72 hours after the last administration of Rifampicin acute renal failure developed in all five cases. Two of the patients also had signs of liver failure (increased serum transaminase, lowered pseudo-cholinesterase, increased BSP retention), and in one of them there was also a hematological syndrome consisting in hemolytic anemia and thrombocytopenia. Four of the patients benefited from application of diuretics, hydroelectrolytic re-equilibration and/or hemodialysis. One of the subjects died 12 hours after being hospitalized, with acute pulmonary oedema, refractory to treatment. From the histopathological viewpoint glomerular lesions were found in the kidney (non-uniform thickening of the basal membranes by PAS-positive deposits). In two of the patients various immunological tests have been carried out (Coombs test, lymphocyte-migration inhibition, serum and urine immunelectrophoresis) that, by their alterations, provide some elements indicating the immunological origin of the phenomena.
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PMID:[Severe complications following intermittent administration of rifampicin]. 18 3

Transfusion of platelet concentrates was used to establish a thrombocytosis of approximately three times normal platelet levels in male rats. This thrombocytosis resulted in a rebound thrombocytopenia to 60% of normal counts. Examination of the small acetylcholinesterase (ACh-E) positive cells of the marrow at this time showed a reduction to 50% of normal levels without significant changes in control animals. A second group of experiments indicated that this suppression developed as early as the third day posttransfusion, persisted until day 7, and returned to baseline levels by day 9. Incorporation of 75SeM indicated that the reduction in platelet count was due to decreased platelet production. Little or no changes were observed in the hematocrit or WBC. This evidence supports the hypothesis that these cells are early cells in the megakaryocytic series. They are the earliest cells of the series seen to be affected by thrombocytosis. Feedback control by platelets or platelet extracts of this cell population may represent one level of regulation of megakaryopoiesis.
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PMID:Thrombocytosis-induced suppression of small acetylcholinesterase-positive cells in bone marrow of rats. 50 41

The ACHE and BCHE genes, encoding the acetylcholine hydrolysing enzymes acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE), co-amplify with several oncogenes in leukemic patients with platelet deficiency (thrombocytopenia). This and other experiments implicated ACHE and BCHE in the development of bone marrow megakaryocytes, the progenitors of platelets. Therefore, we wished to find out whether cholinesterase gene amplification would also occur in non-cancerous platelet disorders and, if so, whether oncogenes would amplify in such cases as well. The autoimmune disease systemic lupus erythematosus (SLE) presents an appropriate model system for this issue, since patients with SLE may suffer from thrombocytopenia resistant to most treatment modalities. Here, we report a 40-80-fold amplification of genomic sequences from the ACHE and BCHE genes as well as the C-raf, V-sis and C-fes/fps oncogenes in peripheral blood cells from an SLE patient with severe thrombocytopenia. PvuII restriction analysis and DNA blot hybridization of the amplified ACHE and BCHE sequences demonstrated apparent aberrations in both genes, suggesting that malfunctioning of modified, partially amplified cholinesterase genes may be involved in the etiology of thrombocytopenia associated with SLE. These observations imply that cholinergic mechanisms regulate megakaryocytopoiesis, shed new light on the diverse hematologic findings characteristic of SLE, and may become valuable as diagnostic, treatment and prognostic tools in the follow-up of patients suffering from thrombocytopenia associated with SLE. Furthermore, these findings reinforce the notion that cholinesterase gene amplifications are causally related with platelet abnormalities in multiple hemopoietic disorders.
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PMID:In vivo gene amplification in non-cancerous cells: cholinesterase genes and oncogenes amplify in thrombocytopenia associated with lupus erythematosus. 137 19

Using murine platelets as an immunogen, a rat monoclonal antibody (designated 4A5) that recognizes only murine blood platelets and marrow megakaryocytes was developed. The extent of binding of 4A5 to platelets was dependent upon their state of activation. Following phorbol ester, ionophore, or thrombin stimulation of resting platelets, a decrease of > 50% in the binding of 4A5 was observed by flow cytometry. This decrease in antibody binding to the platelets was accompanied by an increase in antibody released into the platelet-free supernatant following platelet activation. When platelets were first radioiodinated, followed by activation and incubation of the platelet-free supernatant with 4A5-derivatized beads, no precipitable counts were observed compared with control resting platelets. This suggests that antibody release was related to an activation-dependent conformational change in the 4A5 epitope. Following solubilization of biotinylated platelets, 4A5 bound to an 80-kd membrane protein. Immunohistochemical studies with 4A5 showed that megakaryocytes could be identified both in vitro and ex vivo. When marrow was first stained histochemically with 4A5 followed by staining for acetylcholinesterase, the distribution of stained cells was similar. Flow cytometric analysis using 4A5 and propidium iodide showed that the antibody could be used to identify megakaryocytes for ploidy analysis in vivo or in vitro. 4A5 was capable of inducing a moderate thrombocytopenia in mice compared with polyclonal anti-platelet serum. When bound to plastic or to magnetic beads, 4A5 could be used to purify murine megakaryocytes to homogeneity. The data suggest that monoclonal antibody 4A5 will be useful in quantitative studies of murine platelets and megakaryocytes.
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PMID:Characteristics of a novel rat anti-mouse platelet monoclonal antibody: application to studies of megakaryocytes. 142 96

Thrombocytopenia in general, and autoimmune thrombocytopenia in particular, is a disease of high prevalence with a non-satisfactory regime of treatment. The present study aimed to explore the feasibility of an alternative treatment, based on the rationale that autologous erythrocytes modified to bear covalently bound fibrinogen would participate passively in the aggregation of the remaining platelets, thus augmenting the haemostatic needs, while resisting the autoimmune reaction directed towards the platelets. Several procedures for the cross-linking of fibrinogen to red blood cells (RBCs) were tested. Formaldehyde (33 microM) for 10 min at 23 degrees C attached 58 fibrinogen molecules per erythrocyte. These erythrocytes were indistinguishable from untreated erythrocytes in the following properties: osmotic fragility, bound haemoglobin, sedimentation rate, acetylcholinesterase activity, phagocytosis by macrophages, rosette formation with K562 cells. It is shown that RBCs cross-linked with fibrinogen are capable of participating in the in vitro aggregation of platelets and are indeed effective in the in vivo process of arrest of bleeding in an animal model of autoimmune thrombocytopenia.
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PMID:Erythrocytes with covalently bound fibrinogen as a cellular replacement for the treatment of thrombocytopenia. 157 88

The Belgrade laboratory (b/b) rat has a hereditary hypochromic microcytic anemia because of defective transmembrane iron transport into erythroblasts. The present study was prompted by our previous work in which we showed that the b/b rat has hypomegakaryocytic thrombocytopenia associated with increased megakaryocyte size. To define the basic mechanism underlying this abnormality in the b/b rat we have studied both megakaryocytopoiesis and granulopoiesis in anemic b/b rats, chronically transfused b/b rats, iron-treated b/b rats, and controls. We have found decreased concentrations of megakaryocyte and granulocyte progenitors in the marrow of b/b rats. Full correction of the severe anemia by chronic transfusion resulted in normalization of megakaryocyte progenitors, small acetylcholinesterase positive cells, megakaryocyte size, and platelet counts, along with granulocyte progenitors. In contrast, the partial correction of anemia obtained by iron treatment resulted in improvement, but not normalization, of these parameters. These findings indicate that abnormal megakaryocytopoiesis in the b/b rat can be best interpreted as a consequence of hypoxia because of the severe anemia. Because we have recently shown that the number of erythroid progenitors in b/b rats is also low, we propose that abnormal megakaryocytopoiesis in this animal is a reflection of an acquired stem cell disorder induced by the prolonged hypoxia resulting from the severe anemia.
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PMID:Abnormal megakaryocytopoiesis in the Belgrade laboratory rat. 199 Nov 62

Paroxysmal nocturnal hemoglobinuria, first described in the late 19th century, is an acquired disorder characterized by hemoglobinemia and hemoglobinuria. The major clinical manifestation of PNH is chronic intravascular hemolysis of various severity. Patients-mostly young adults - may also present with episodes of abdominal or back pain. Common cause of death is thrombosis especially of the hepatic veins. Granulocytopenia and thrombocytopenia may be the initial manifestation of PNH, indicating that the disorder is a primary bone-marrow disease, affecting not only the erythrocytes but also other peripheral blood cells and the haematopoietic stem cell. The course of the disease is variable. Partial complete recovery was described, but also fatal thrombosis. The major phenotypic expression of PNH is an increased susceptibility of the erythrocytes to the lytic action of complement in vitro. The enhanced complement susceptibility is most probably due to membrane defects: two membrane proteins regulating the complement cascade in PNH cells were missing, the decay-accelerating factor, DAF, inhibiting the activation of the lytic complement complex and the C8 binding protein, C8bp, which interferes with the lytic process. Aside from the lack of the complement regulators also other membrane defects have been described (e.g. of acetylcholinesterase or alkaline phosphatase). The proteins as well as DAF and C8bp are linked to the cell membrane via a phosphatidylinositol (PI) anchor, leading to the speculation that the disease results from a deficiency in the post-translational PI anchoring mechanism. The diagnosis of PNH is based on the Hamtest, but will be extended to the quantitation of the above described membrane proteins.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Paroxysmal nocturnal hemoglobinuria]. 218 38

To examine the pathogenesis of thrombocytopenia associated with liver cirrhosis, the platelet count, spleen size and serum cholinesterase levels were measured together with plasma concentration of beta-thromboglobulin, fibrinopeptide A and serum albumin in 38 patients with histologically proven, severe but stable liver cirrhosis. The spleen size contributed most significantly to thrombocytopenia in this disorder and the serum cholinesterase level also correlated with the platelet count, both in decompensated and compensated liver cirrhosis. Plasma beta-thromboglobulin, serum fibrinopeptide A levels and serum albumin did not correlate with the platelet count. These findings indicate that disseminated intravascular coagulation is not likely to be the cause of thrombocytopenia in liver cirrhosis. Splenomegaly as well as the diminished protein synthetic activity of the liver participates in the pathogenesis of the thrombocytopenia in this disease.
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PMID:Thrombocytopenia in liver cirrhosis. 261 53

IL-1 has been shown to stimulate the release of granulocyte-macrophage CSF, granulocyte-CSF, and macrophage-CSF from "accessory cell populations" in vitro, and it stimulates the appearance of colony-stimulating activity in the sera of mice in vivo. This cytokine has also been proposed to act on primitive hematopoietic progenitor cells to stimulate expression of receptors for the CSF. We sought to determine whether IL-1 beta could influence platelet and/or megakaryocytes and their progenitor cells following in vivo administration to normal mice. Our results demonstrated that, although administration of IL-1 beta clearly expands the pool of megakaryocyte-CFU and acetylcholinesterase-positive megakaryocytic cells (primarily in the spleen), it causes a transient and dose-dependent reduction of circulating platelets. The associated thrombocytopenia can be abolished by splenectomy before IL-1 beta administration, and is not temporally associated with the development of splenomegaly.
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PMID:Alterations in megakaryocyte and platelet compartments following in vivo IL-1 beta administration to normal mice. 278 31

The number of small acetylcholinesterase-positive (SAChE+) cells in the marrow of hypoxic mice was measured. Mice were exposed to 6-7% O2 levels by enclosure in cages covered with dimethyl-silicone rubber membranes for 1-14 days. The mice showed a linear increase in packed cell volumes with time in the hypoxic atmosphere, but platelet counts showed a characteristic biphasic response, i.e., increased platelet counts were observed after 1-3 days of hypoxia, and significantly (P less than 0.05-P less than 0.0005) decreased platelet counts were observed thereafter (6-14 days). The total number of megakaryocytes in the marrow of hypoxic mice decreased significantly (P less than 0.005) with time. In agreement with the data on platelet counts, hypoxia caused the total number of SAChE+ cells in the marrow of mice to be biphasic. At Day 2 there was a significant increase (P less than 0.05) in the total number of SAChE+ cells/mm3 of bone marrow; however, by days 10-14 the numbers had decreased markedly (P less than 0.005). These data indicate that hypoxia decreases platelet production by action on a precursor cell to the SAChE+ cell. The hypoxia-induced thrombocytopenia is probably caused by stem-cell competition between the erythrocytic and megakaryocytic cell lines.
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PMID:Effects of hypoxia on the small acetylcholinesterase-positive megakaryocyte precursor in bone marrow of mice. 374 28


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