Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Actin and myosin have been isolated from a guinea pig B cell leukemia line, L2C. The m.w. and amino acid compositions of these proteins are similar to actin and myosin from other nonmuscle cell types. L2C actin polymerizes to form filaments and activates the ATPase activity of skeletal muscle myosin. Actin in crude lymphocyte extracts does not polymerize as well as predicted from the critical concentration of purified lymphocyte actin suggesting that other factors in lymphocyte extracts regulate actin polymerization. Lymphocyte myosin polymerizes to form synthetic filaments at low ionic strength. Lymphocyte myosin binds to actin, but its ATPase activity is not activated by actin. Possible mechanisms for regulation of the lymphocyte contractile apparatus and its importance in a number of lymphocyte functions are discussed.
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PMID:Isolation and characterization of actin and myosin from B-lymphocytic guinea pig leukemia cells. 15 29

A detailed kinetic analysis of the distribution of cytoplasmic myosin during the capping of various lymphocytic surface molecules revealed two distinct capping mechanisms. (a) Some cell surface molecules, including immunoglobulin, Fc receptor, and thymus leukemia antigen, all cap spontaneously in a small fraction of lymphocytes during locomotion. Cytoplasmic myosin becomes concentrated in the cytoplasm underlying these spontaneous caps. Exposure to specific antibodies causes all three of these surface molecules to cap rapidly with a concomitant redistribution of cytoplasmic myosin to the area of the cap. These antibodies also stimulate cell locomotion. (b) Other lymphocyte surface molecules, including H2 and Thy.1, do not cap spontaneously. Moreover, exposure to antibodies to these molecules causes them to cap slowly without a redistribution of cytoplasmic myosin or stimulation of cell locomotion. Exposure to concanavalin A gives a response intermediate between these two extremes. We believe that the first type of capping is active and may involve a direct link between the surface molecules and the cytoplasmic contractile apparatus. The second type of capping appears to result simply from aggregation of cross-linked molecules in the plane of the membrane.
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PMID:Two distinct mechanisms for redistribution of lymphocyte surface macromolecules. I. Relationship to cytoplasmic myosin. 30 87

Wortmannin, a specific inhibitor of myosin light chain kinase (MLCK) blocked IgE mediated histamine release from rat basophilic leukemia cell (RBL-2H3) and human basophils dose-dependently. Its IC50 was 20 nM for RBL-2H3 cells and 30 nM for human basophils. There was complete inhibition at the concentration of 1 microM. Wortmannin inhibited partially the A23187 induced histamine release from RBL-2H3 cells (40% inhibition at 1 microM). This inhibition was not accompanied by any significant effect on cytosolic free calcium concentration [( Ca2+]i). KT5926, another MLCK inhibitor, inhibited histamine release comparably with wortmannin and blocked to some degree the increase of [Ca2+]i in RBL-2H3 cells. Thus, the phosphorylation of myosin seems to be involved in signal transduction through Fc epsilon RI.
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PMID:Inhibition of IgE-mediated histamine release by myosin light chain kinase inhibitors. 137 21

A total of 14 well differentiated rhabdomyosarcomas were diagnosed at necropsy in 10,000 mice. Of the 14 affected mice, ten were BALB/cJ, and there was one case each of A/HeJ, BALB/cByJ, C58/J, and C.B-17-scid/scid strains. Most often (10/14) tumors originated in the quadriceps muscles and metastases occurred in six cases. When submitted, affected mice were 2 to 8 months of age, with a mean age of 4 months. Tumor frequency for BALB/cJ mice was calculated to be 2.4/100,000 mice retained as breeders. No sexual dimorphisms were determined when data were correlated to actual numbers of each sex in the colony. All 14 primary tumors and metastases were positive by immunohistochemistry for the proteins pan myosin, sarcomeric actin, desmin, actin, and myosin, but were negative for smooth muscle actin, thus confirming the diagnosis. Using cell free homogenates of primary tumors, inoculated by intraperitoneal or intramuscular injection, tumors were not induced in either BALB/cJ or C58/J mice observed over a 22-week period. Southern blot analysis of DNA prepared from tumors and hybridized with a murine leukemia virus probe that recognizes both ecotropic and dualtropic viruses did not demonstrate viral genomic fragments in addition to those known to occur in each strain.
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PMID:Skeletal muscle rhabdomyosarcomas in inbred laboratory mice. 183 Apr 33

Hundreds of murine dilute mutations have been identified and analysed, making dilute one of the best genetically characterized of all mammalian loci. The recessive dilute (d) coat colour mutation carried by many inbred strains of mice produces a lightening of coat colour, caused by an abnormal adendritic melanocyte morphology that results in an uneven release of pigment granules into the developing hair shaft. Most dilute alleles (dilute-lethal) also produce a neurological defect, characterized by convulsions and opisthotonus, apparent at 8-10 days of age and continuing until the death of the animal at 2-3 weeks of age. The discovery that the original dilute allele (now termed dilute-viral or dV) is the result of the integration of an ecotropic murine leukaemia provirus has allowed the cloning of genomic DNA and in this study complementary DNA, from the dilute locus. The predicted dilute amino-acid sequence indicates that dilute encodes a novel type of myosin heavy chain, with a tail, or C-terminal, region that has elements of both type II (alpha-helical coiled-coil) and type I (non-coiled-coil) myosin heavy chains. Dilute transcripts are differentially expressed in both embryonic and adult tissues and are very abundant in neurons of the central nervous system, cephalic ganglia, and spinal ganglia. These results suggest an important role for the dilute gene product in the elaboration, maintenance, or function of cellular processes of melanocytes and neurons.
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PMID:Novel myosin heavy chain encoded by murine dilute coat colour locus. 199 38

Different kinds of leukocytes undergo cytoskeleton-dependent mechanical responses associated with their specific physiological functions. We have investigated cellular stiffening of several types of leukocytes using a method which measures the force resisting cellular indentation. We have found that lymphocytes stiffen in response to crosslinking cell surface antigens in a process associated with the much studied capping and patching processes. Further studies of myosin-deficient mutants of the ameba Dictyostelium discoideum suggest that this stiffening process results from a myosin dependent contractile process. Rat basophilic leukemia cells and pancreatic islet cells stiffen when triggered to secrete. The function of these cytoskeleton dependent processes is now unknown, but, at least in the islet cells, may be related to a regulation of the rate of secretion. Primary neutrophils stiffen in response to the chemotactic agent, fMet-Leu-Phe. This stiffening may be responsible for retention of these cells in the pulmonary microcirculation during response to inflammation. These observations pose the challenge of determining the structural basis, mechanism, and physiological function of each of these cellular responses.
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PMID:Activation of mechanical responses in leukocytes. 209 93

Thyroid hormone-induced changes in cardiac function have been recognized for over 150 years; however, the biochemical basis of triiodothyronine (T3) action in the heart has been intensely investigated only during the last two decades. T3-induced changes in cardiac function can result from direct or indirect T3 effects. Direct T3 effects result from T3 action in the heart itself and are mediated by nuclear or extranuclear mechanisms. Extranuclear T3 effects, which occur independent of nuclear T3 receptor binding and increases in protein synthesis, influence primarily the transport of amino acids, sugars, and calcium across the cell membrane. Nuclear T3 effects are mediated by the binding of T3 to specific nuclear receptor proteins, which results in increased transcription of T3-responsive cardiac genes. The T3 receptor is a member of the ligand-activated transcription factor family and is encoded by cellular erythroblastosis A (c-erb A) genes. The c-erb A protein is the cellular homologue of the viral erythroblastosis A (v-erb A) protein, which causes red cell leukemia in chickens. Currently, three T3-binding isoforms of the c-erb protein and two non-T3-binding nuclear proteins that exert positive and negative effects on T3-responsive cardiac genes have been identified. T3 increases the heart transcription of the myosin heavy chain (MHC) alpha gene and decreases the transcription of the MHC beta gene, leading to an increase of myosin V1 and a decrease in myosin V3 isoenzymes. Myosin V1, which is composed of two MHC alpha, has a higher myosin ATPase activity than myosin V3, which contains two MHC beta. The globular head of myosin V1, with its higher ATPase activity, leads to a more rapid movement of the globular head of myosin along the thin filament, resulting in an increased velocity of contraction. T3 also leads to an increase in the speed of diastolic relaxation, which is caused by the more efficient pumping of the calcium ATPase of the sarcoplasmic reticulum (SR). This T3 effect results from T3-induced increases in the level of the mRNA coding for the SR calcium ATPase protein, leading to an increased number of calcium ATPase pump units in the SR. Overall, thyroid hormone leads to an increase in ATP consumption in the heart. In addition, less chemical energy of ATP is used for contractile purposes and more of it goes toward heat production, which causes a decreased efficiency of the contractile process in the hyperthyroid heart.
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PMID:Biochemical basis of thyroid hormone action in the heart. 218 6

IgE-mediated stimulation of rat basophilic leukemia (RBL-2H3) cells results in the secretion of histamine. Myosin immunoprecipitated from these cells shows an increase in the amount of radioactive phosphate incorporated into its heavy (200 kDa) and light (20 kDa) chains. In unstimulated cells two-dimensional mapping of tryptic peptides of the myosin light chain reveals one phosphopeptide containing the serine residue phosphorylated by myosin light chain kinase. Following stimulation a second phosphopeptide appears containing a serine residue phosphorylated by protein kinase C. Tryptic phosphopeptide maps derived from myosin heavy chains show that unstimulated cells contain three major phosphopeptides. Following stimulation a new tryptic phosphopeptide appears containing a serine site phosphorylated by protein kinase C. The stoichiometry of phosphorylation of the myosin light and heavy chains was determined before and after antigenic stimulation. Before stimulation, myosin light chains contained 0.4 mol of phosphate/mol of light chain all confined to a serine not phosphorylated by protein kinase C. Cells that secreted 44% of their total histamine in 10 min exhibited an increase in phosphate content at sites phosphorylated by protein kinase C from 0 mol of phosphate/mol of myosin subunit to 0.7 mol of phosphate/mol of light chain and to 1 mol of phosphate/mol of heavy chain. When RBL-2H3 cells were made permeable with streptolysin O they still showed a qualitatively similar pattern of secretion and phosphorylation. Our results show that the time course of histamine secretion from stimulated RBL-2H3 cells parallels that of myosin heavy and light chain phosphorylation by protein kinase C.
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PMID:Antigen-induced secretion of histamine and the phosphorylation of myosin by protein kinase C in rat basophilic leukemia cells. 247 73

We have found that phosphorylation of the 18,000 mol. wt protein in rat basophilic leukemia cells (RBL-2H3 cells) is enhanced by stimulation by an antigen. This phenomenon was also observed when cells were treated with phorbol myristate (TPA) and a calcium ionophor, A23187. The phosphorylated 18,000 mol. wt protein was mainly located in the membrane fraction. It was identified as one of the myosin light chains as follows: (1) the mol. wt of one of the major myosin light chains of RBL-2H3 cells was 18,000; (2) more than half of the phosphorylated 18,000 mol. wt protein was recovered in an actomyosin fraction; (3) this phosphorylated 18,000 mol. wt protein was immunoprecipitated with anti-myosin antibody. Since the presence of Ca2+ in the cell culture medium was essential for the phosphorylation of the 18,000 mol. wt protein and, since trifluoperazine (a potent inhibitor of calmodulin as well as of the degranulation process of RBL-2H3 cells) inhibited the reaction, the phosphorylation may be catalyzed by a Ca2+-calmodulin-dependent process, most likely by myosin light chain kinase. These results, together with our previous observation [Teshima et al. Molec Immun. 23, 279-284 (1986)], suggest that simultaneous phosphorylation of the 18,000 mol. wt myosin light chain and a 36,000 mol. wt membranous protein is a prerequisite for the degranulation of RBL-2H3 cells.
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PMID:Enhancement of the phosphorylation of membrane bound myosin light chain by antigen stimulation in rat basophilic leukemia cells. 277 87

Twenty-two patients (acute myeloid leukaemia 13, acute lymphoid leukaemia 5, chronic myeloid leukaemia 4) with an average age of 25 years (range 8-36 years), had received allogeneic bone marrow transplantation (BMT) from an HLA identical sibling. The BMT recipients were followed up for a period of 4-65 months. All patients were given cyclophosphamide, total body irradiation and methotrexate in order to prevent graft-versus-host disease (GvHD). Eleven of 22 patients exhibited chronic graft versus host disease (cGvHD) (extensive in five, limited in six at the time of the study) assessed by clinical and histological parameters. Serum samples were collected from these patients, before BMT (except in one case) and then every 2 or 3 months. Sequential studies to determine the presence of autoantibodies against cytoskeletal proteins (actin, tubulin, myosin), dsDNA and dDNA in these sera were performed by an ELISA method. Simultaneously, immunoelectrophoresis and measurement of complement fractions C3, C4 were performed on each sample. High levels of autoantibodies against cytoskeletal proteins were found in 10/11 patients with cGvHD and were absent in 11/11 patients without cGvHD; none of them exhibited anti-DNA activity. At the same time, C4 levels were decreased in seven of these patients with cGvHD. Monoclonal immunoglobulins IgG and IgM (2-15 g/l) were found in 8/11, but the antibody activity was never found to be located within the M component. These results show a direct relationship between the presence of these autoantibodies and occurrence of cGvHD and indicate that they may constitute an immunological marker related to this complication. However, their predictive value is not clearly evident in this retrospective series as in some patients they preceded clinical signs of cGvHD, whereas in others they were associated with the onset of cGvHD.
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PMID:High levels of anti-cytoskeleton autoantibodies are frequently associated with chronic GVHD. 331 12


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