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Sample records for rat basophilic leukemia

  1. Phospholipase A/sub 2/ stimulation during cell secretion in rat basophilic leukemia cells

    SciTech Connect

    Garcia-Gil, M.; Siraganian, R.P.

    1986-01-01

    The bridging of IgE receptors on rat basophilic leukemia cells (RBL-2H3) results in a number of biochemical events that accompany histamine secretion. Prominent among these is the release of arachidonic acid from cellular phospholipids, which could be due to the activation of phospholipase enzymes. In the present experiments they studied the intracellular activation of phospholipase A/sub 2/ (PLA/sub 2/) during histamine release. The enzyme in the homogenates was capable of cleaving arachidonic acid from different phospholipids. The production of lysophospholipids could play a critical role in histamine release from cells. These results demonstrate the activation of PLA/sub 2/ enzyme in cellular homogenates during the secretory process.

  2. Screening anaphylactic components of MaiLuoNing injection by using rat basophilic leukemia-2H3 cell membrane chromatography coupled with HPLC-ESI-TOF-MS.

    PubMed

    Han, Shengli; Lv, Yanni; Xue, Wenjing; Cao, Jiao; Cui, Ronghua; Zhang, Tao

    2016-02-01

    MaiLuoNing injection is a traditional Chinese medicine that used clinically since the 1950s in China. However, anaphylactic reactions, through the potentiation of mast cell degranulation, have been reported. In the present study, a rat basophilic leukemia-2H3 cell membrane chromatography coupled with high-performance liquid chromatography and electrospray ionization-ion trap-time of flight-mass spectrometry method was established for screening, analyzing, and identifying the potential anaphylactic components of MaiLuoNing injection. Harpagoside, a potential degranulator of rat basophilic leukemia-2H3 cells, was retained in rat basophilic leukemia-2H3 cell membrane chromatography. We aimed to evaluate the retained components to determine which of those were capable of inducing degranulation of basophilic leukemia cells. A β-hexosaminidase assay revealed that harpagoside can induce rat basophilic leukemia-2H3 cell degranulation in a dose-dependent manner. BLBA/c mice also exhibit passive cutaneous anaphylaxis in response to harpagoside. These results indicate that rat basophilic leukemia-2H3 cell membrane chromatography coupled with high-performance liquid chromatography and electrospray ionization ion trap time-of-flight mass spectrometry is effective in screening for the anaphylactic components of MaiLuoNing injection.

  3. Engineered Nanostructures of Haptens Lead to Unexpected Formation of Membrane Nanotubes Connecting Rat Basophilic Leukemia Cells

    DOE PAGES

    Li, Jie-Ren; Ross, Shailise S.; Liu, Yang; ...

    2015-06-09

    We report here on a recent finding that co-stimulation of the high-affinity immunoglobulin E (IgE) receptor (FcεRI) and the chemokine receptor 1 (CCR1) triggered formation of membrane nanotubes among bone-marrow-derived mast cells. The co-stimulation was attained using corresponding ligands: IgE binding antigen and macrophage inflammatory protein 1α (MIP1 α), respectively. However, this approach failed to trigger formation of nanotubes among rat basophilic leukemia (RBL) cells due to the lack of CCR1 on the cell surface (Int. Immunol. 2010, 22 (2), 113–128). RBL cells are frequently used as a model for mast cells and are best known for antibody-mediated activation viamore » FcεRI. This work reports the successful formation of membrane nanotubes among RBLs using only one stimulus, a hapten of 2,4-dinitrophenyl (DNP) molecules, which are presented as nanostructures with our designed spatial arrangements. This observation underlines the significance of the local presentation of ligands in the context of impacting the cellular signaling cascades. In the case of RBL, certain DNP nanostructures suppress antigen-induced degranulation and facilitate the rearrangement of the cytoskeleton to form nanotubes. We conclude that these results demonstrate an important scientific concept; engineered nanostructures enable cellular signaling cascades, where current technologies encounter great difficulties. More importantly, nanotechnology offers a new platform to selectively activate and/or inhibit desired cellular signaling cascades.« less

  4. Engineered Nanostructures of Haptens Lead to Unexpected Formation of Membrane Nanotubes Connecting Rat Basophilic Leukemia Cells

    SciTech Connect

    Li, Jie-Ren; Ross, Shailise S.; Liu, Yang; Liu, Ying X.; Wang, Kang-hsin; Chen, Huan-Yuan; Liu, Fu-Tong; Laurence, Ted A.; Liu, Gang-yu

    2015-06-09

    We report here on a recent finding that co-stimulation of the high-affinity immunoglobulin E (IgE) receptor (FcεRI) and the chemokine receptor 1 (CCR1) triggered formation of membrane nanotubes among bone-marrow-derived mast cells. The co-stimulation was attained using corresponding ligands: IgE binding antigen and macrophage inflammatory protein 1α (MIP1 α), respectively. However, this approach failed to trigger formation of nanotubes among rat basophilic leukemia (RBL) cells due to the lack of CCR1 on the cell surface (Int. Immunol. 2010, 22 (2), 113–128). RBL cells are frequently used as a model for mast cells and are best known for antibody-mediated activation via FcεRI. This work reports the successful formation of membrane nanotubes among RBLs using only one stimulus, a hapten of 2,4-dinitrophenyl (DNP) molecules, which are presented as nanostructures with our designed spatial arrangements. This observation underlines the significance of the local presentation of ligands in the context of impacting the cellular signaling cascades. In the case of RBL, certain DNP nanostructures suppress antigen-induced degranulation and facilitate the rearrangement of the cytoskeleton to form nanotubes. We conclude that these results demonstrate an important scientific concept; engineered nanostructures enable cellular signaling cascades, where current technologies encounter great difficulties. More importantly, nanotechnology offers a new platform to selectively activate and/or inhibit desired cellular signaling cascades.

  5. Source of the arachidonic acid released on stimulation of rat basophilic leukemia cells

    SciTech Connect

    Garcia-Gil, M.; Siraganian, R.P.

    1986-05-15

    Triggering of rat basophilic leukemia cells for histamine secretion is accompanied by arachidonic acid release. The source of this arachidonic acid released after IgE or calcium ionophore A23187 stimulation was studied. The 48-hr culture of the cells with (/sup 14/C)arachidonic acid resulted in labeling of the phospholipids to constant specific activity. After IgE stimulation, 8.8% of the cellular (/sup 14/C)arachidonate was released; this was predominantly from phosphatidylinositol (PI)/phosphatidylserine (PS) (66.3%), less from phosphatidylethanolamine (PE) (25.9%), and minimally from phosphatidylcholine (PC). In contrast, after ionophore stimulation the cells released 16.4% of cellular (/sup 14/C)arachidonate, most of this was from PE (55.4%) followed by about equal amounts from PS/PI and PC (24% and 20%, respectively). Therefore, the source of the released arachidonic acid depends on the stimulus. In contrast, the results are different when the cells are cultured for only 2 hr with (/sup 14/C)arachidonic acid. The label in phospholipids was in PC (44%), PE (38%), and PI/PS (20%); the stimulation of the cells with IgE or ionophore resulted in the release of the (/sup 14/C)arachidonate from PC (81% and 96%, respectively). This suggests the presence of several pools of phospholipids that are labeled at different rates and have variable proximity and/or accessibility to the phospholipase(s) enzyme(s) activated during cell secretion.

  6. In vitro stimulation with a strongly pulsed electromagnetic field on rat basophilic leukemia cells

    NASA Astrophysics Data System (ADS)

    Choi, J. W.; Shin, S. C.; Kim, S.; Chung, E. R.; Bang, J. H.; Cho, G. I.; Choi, S. D.; Park, Y. S.; Jang, T. S.; Yoo, Y. M.; Lee, S. S.; Hwang, D. G.

    2010-05-01

    In this study, the effects of pulsed electromagnetic field stimulation with a strong magnetic field on rat basophilic leukemia (RBL-2H3) cells were investigated to confirm the efficacy of the magnetic stimulator for biomedical applications. The maximum intensity of the magnetic field generated from the stimulation coil was 0.203 T, and the transition time was 126 μs. The oscillation time and frequency of the pulsed field were almost 0.1 ms and 8 kHz, respectively. The cell count as well as the mRNA expression and DNA sequence of the cytokine genes, such as the tumor necrosis factor-α (TNF-α) and interleukin-4 (IL-4), of the stimulated RBL-2H3 cells were analyzed with a hemocytometer and via reverse transcriptase polymerase chain reaction to determine the physiological response under a strong pulse field. After 12 h stimulation, cell death was observed at an increasing scale with the increase in the stimulation time. On the other hand, the cells that were stimulated for 10 min almost doubled as the interval time between the stimulations was extended.

  7. Screening antiallergic components from Carthamus tinctorius using rat basophilic leukemia 2H3 cell membrane chromatography combined with high-performance liquid chromatography and tandem mass spectrometry.

    PubMed

    Han, Shengli; Huang, Jing; Cui, Ronghua; Zhang, Tao

    2015-02-01

    Carthamus tinctorius, used in traditional Chinese medicine, has many pharmacological effects, such as anticoagulant effects, antioxidant effects, antiaging effects, regulation of gene expression, and antitumor effects. However, there is no report on the antiallergic effects of the components in C. tinctorius. In the present study, we investigated the antiallergic components of C. tinctorius and its mechanism of action. A rat basophilic leukemia 2H3/cell membrane chromatography coupled online with high-performance liquid chromatography and tandem mass spectrometry method was developed to screen antiallergic components from C. tinctorius. The screening results showed that Hydroxysafflor yellow A, from C. tinctorius, was the targeted component that retained on the rat basophilic leukemia 2H3/cell membrane chromatography column. We measured the amount of β-hexosaminidase and histamine released in mast cells and the key markers of degranulation. The release assays showed that Hydroxysafflor yellow A could attenuate the immunoglobulin E induced release of allergic cytokines without affecting cell viability from 1.0 to 50.0 μM. In conclusion, the established rat basophilic leukemia 2H3 cell membrane chromatography coupled with online high-performance liquid chromatography and tandem mass spectrometry method successfully screened and identified Hydroxysafflor yellow A from C. tinctorius as a potential antiallergic component. Pharmacological analysis elucidated that Hydroxysafflor yellow A is an effective natural component for inhibiting immunoglobulin E-antigen-mediated degranulation.

  8. Inhibitory effects of norlignans isolated from Anemarrhena asphodeloides on degranulation of rat basophilic leukemia- 2H3Cells.

    PubMed

    Bak, Jong Phil; Cho, Young Mi; Kim, Inhye; Park, Dae Won; Kwon, Jung Eun; Jeong, Yong Joon; Kwak, Jong Hwan; Kang, Se Chan

    2016-12-01

    Anemarrhena asphodeloides is known to suppress inflammation and lower various fevers. To determine the active component of A. asphodeloides, ethanol (EtOH) extract of A. asphodeloides rhizomes was fractionized. The compounds isolated from the dichloromethane (CH2Cl2) soluble fraction were identified as 4'-O-methylnyasol (1), nyasol (2), 3″-methoxynyasol (3), 3″-hydroxy-4″-methoxy-4″-dehydroxynyasol (4), 4-hydroxybenzaldehyde (5), and 4-hydroxyacetophenone (6). The four norlignans (1-4) potently inhibited the release of β-hexosaminidase from immunoglobulin E (IgE)/dinitrophenol-conjugated bovine serum albumin (DNP-BSA)-treated rat basophilic leukemia (RBL)-2H3 and A23187 plus phorbol 12-myristate 13-acetate co-treated isolated rat primary mast cells, as markers of degranulation and histamine release. The intraperitoneal treatment with the EtOH extract significantly suppressed the fetal reaction, and serum histamine release induced by compound 48/80 in mice. These results suggest that the four active norlignan compounds and the EtOH extract of A. asphodeloides may have potential to be developed as medicines for the treatment of allergies by inhibiting the activation of mast cells.

  9. Distribution and Dynamics of Rat Basophilic Leukemia Immunoglobulin E Receptors (FcɛRI) on Planar Ligand-Presenting Surfaces

    PubMed Central

    Spendier, Kathrin; Carroll-Portillo, Amanda; Lidke, Keith A.; Wilson, Bridget S.; Timlin, Jerilyn A.; Thomas, James L.

    2010-01-01

    Abstract There is considerable interest in the signaling mechanisms of immunoreceptors, especially when triggered with membrane-bound ligands. We have quantified the spatiotemporal dynamics of the redistribution of immunoglobulin E-loaded receptors (IgE-FcɛRI) on rat basophilic leukemia-2H3 mast cells in contact with fluid and gel-phase membranes displaying ligands for immunoglobulin E, using total internal reflection fluorescence microscopy. To clearly separate the kinetics of receptor redistribution from cell spreading, and to precisely define the initial contact time (±50 ms), micropipette cell manipulation was used to bring individual cells into contact with surfaces. On ligand-free surfaces, there are micron-scale heterogeneities in fluorescence that likely reflect regions of the cell that are more closely apposed to the substrate. When ligands are present, receptor clusters form with this same size scale. The initial rate of accumulation of receptors into the clusters is consistent with diffusion-limited trapping with D ∼10−1μm2/s. These results support the hypothesis that clusters form by diffusion to cell-surface contact regions. Over longer timescales (>10 s), individual clusters moved with both diffusive and directed motion components. The dynamics of the cluster motion is similar to the dynamics of membrane fluctuations of cells on ligand-free fluid membranes. Thus, the same cellular machinery may be responsible for both processes. PMID:20643056

  10. The effects of thermal stimuli on intracellular calcium change and histamine releases in rat basophilic leukemia mast cells

    NASA Astrophysics Data System (ADS)

    Wu, Zu-Hui; Zhu, Dan; Chen, Ji-Yao; Zhou, Lu-Wei

    2012-05-01

    The effects of thermal stimuli on rat basophilic leukemia mast cells were studied. The cells in calcium-contained or calcium-free buffers were thermally stimulated in the temperature range of 25-60 °C. The corresponding calcium ion concentration in cells [Ca2+]i as well as the released histamine from cells was measured with fluorescence staining methods. The ruthenium red (RR), a block of membrane calcium channels (transient receptor potential family V (TRPV)), was used in experiments. Under the stimulus of 25-50 °C, no significant difference on [Ca2+]i was found between these three groups of the cells in calcium-contained buffer without or with RR and cells in calcium-free saline, indicating that the increased calcium in cytosol did not result from the extracellular buffer but came from the intracellular calcium stores. The [Ca2+]i continuously increased under the temperature of 50-60 °C, but the RR and calcium-free saline can obviously diminish the [Ca2+]i increase at these high temperatures, reflecting that the opening of the TRPV2 channels leads to a calcium influx resulting in the [Ca2+]i increment. The histamine release also became significant in these cases. Since the released histamine is a well-known mediator for the microcirculation promotion, the histamine release from mast cells could be one of the mechanisms of thermal therapy.

  11. Resolution of cellular compartments involved in membrane potential changes accompanying IgE-mediated degranulation of rat basophilic leukemia cells.

    PubMed Central

    Sagi-Eisenberg, R; Pecht, I

    1984-01-01

    The overall membrane potential of rat basophilic leukemia cells (RBL-2H3) calculated from the transmembrane distribution of the lipophilic, tritium-labelled cation tetraphenyl-phosphonium [( 3H]TPP+) was resolved into its mitochondrial and plasma membrane potential components. Using the mitochondrial uncoupler carbonylcyanide-p-trifluormethoxyphenyl hydrazone (FCCP) which collapses the mitochondrial potential, it was shown that about one third of the overall potential resulted from the mitochondrial contribution. Degranulation of the RBL cells induced by two different IgE-cross-linking agents (specific antigen and anti-IgE antibodies), was accompanied by, and well correlated with, a decrease in the overall potential. However, evaluation of the source of these observed potential changes revealed that the FCCP-insensitive fraction of the overall potential, delta psi P, (representing the plasma membrane potential), was not affected. In contrast, the FCCP-sensitive component due to the mitochondrial potential decreased when receptor cross-linking increased. Thus, the observed decrease in the overall potential is most probably a secondary event in the sequence leading from stimulus to secretion. Indeed, exposure of the RBL cells either to a high external concentration of K+ ions or to a high amount of external TPP+, both causing depolarization, failed to trigger degranulation. It is suggested that the apparent decrease in the measured overall potential is a reflection of the mitochondrial membrane depolarization. The latter is most probably caused by mitochondrial Ca2+ uptake initiated by the increase in the intracellular concentration of Ca2+ which follows cells activation. PMID:6232134

  12. The Effects of Electrical Stimuli on Calcium Change and Histamine Release in Rat Basophilic Leukemia Mast Cells

    NASA Astrophysics Data System (ADS)

    Zhu, Dan; Wu, Zu-Hui; Chen, Ji-Yao; Zhou, Lu-Wei

    2013-06-01

    We apply electric fields at different frequencies of 0.1, 1, 10 and 100 kHz to the rat basophilic leukemia (RBL) mast cells in calcium-containing or calcium-free buffers. The stimuli cause changes of the intracellular calcium ion concentration [Ca2+]i as well as the histamine. The [Ca2+]i increases when the frequency of the external electric field increases from 100 Hz to 10 kHz, and then decreases when the frequency further increases from 10 kHz to 100 kHz, showing a peak at 100 kHz. A similar frequency dependence of the histamine release is also found. The [Ca2+]i and the histamine releases at 100 Hz are about the same as the values of the control group with no electrical stimulation. The ruthenium red (RR), an inhibitor to the TRPV (transient receptor potential (TRP) family V) channels across the cell membrane, is used in the experiment to check whether the electric field stimuli act on the TRPV channels. Under an electric field of 10 kHz, the [Ca2+]i in a calcium-concentration buffer is about 3.5 times as much as that of the control group with no electric stimulation, while the [Ca2+]i in a calcium-free buffer is only about 2.2 times. Similar behavior is also found for the histamine release. RR blockage effect on the [Ca2+]i decrease is statistically significant (~75%) when mast cells in the buffer with calcium are stimulated with a 10 kHz electric field in comparison with the result without the RR treatment. This proves that TRPVs are the channels that calcium ions inflow through from the extracellular environment under electrical stimuli. Under this condition, the histamine is also released following a similar way. We suggest that, as far as an electric stimulation is concerned, an application of ac electric field of 10 kHz is better than other frequencies to open TRPV channels in mast cells, and this would cause a significant calcium influx resulting in a significant histamine release, which could be one of the mechanisms for electric therapy.

  13. Kinetics of adhesion of IgE-sensitized rat basophilic leukemia cells to surface-immobilized antigen in Couette flow.

    PubMed Central

    Swift, D G; Posner, R G; Hammer, D A

    1998-01-01

    Antigen-antibody systems provide the flexibility of varying the kinetics and affinity of molecular interaction and studying the resulting effect on adhesion. In a parallel-plate flow chamber, we measured the extent and rate of adhesion of rat basophilic leukemia cells preincubated with anti-dinitrophenyl IgE clones SPE-7 or H1 26. 82 to dinitrophenyl-coated polyacrylamide gel substrates in a linear shear field. Both of these IgEs bind dinitrophenyl, but H1 26.82 has a 10-fold greater on rate and a 30-fold greater affinity. Adhesion was found to be binary; cells either arrested irreversibly or continued at their unencumbered hydrodynamic velocity. Under identical conditions, more adhesion was seen with the higher affinity (higher on rate) IgE clone. At some shear rates, adhesion was robust with H1 26.82, but negligible with SPE-7. Reduction in receptor number or ligand density reduced the maximum level of adhesion seen at any shear rate, but did not decrease the shear rate at which adhesion was first observed. The spatial pattern of adhesion for both IgE clones is well represented by the first-order kinetic rate constant kad, and we have determined how kad depends on ligand and receptor densities and shear rate. The rate constant kad found with H1 26.82 was approximately fivefold greater than with SPE-7. The dependence of kad on site density and shear rate for SPE-7 is complex: kad increases linearly with antigen site density at low to moderate shear rates, but is insensitive to site density at high shear. kad increases with shear rate at low site density but decreases with shear at high site density. With H1 26.82, the functional dependence of kad with shear rate was similar. Although these data are consistent with the hypothesis that we have sampled both transport and reaction-limited adhesion regimes, they point out deficiencies in current theories describing cell attachment under flow. PMID:9788956

  14. OM-X®, Fermented Vegetables Extract Suppresses Antigen-Stimulated Degranulation in Rat Basophilic Leukemia RBL-2H3 Cells and Passive Cutaneous Anaphylaxis Reaction in Mice.

    PubMed

    Itoh, Tomohiro; Miyake, Yasuyoshi; Kasashima, Takuya; Shimomiya, Yoshie; Nakamura, Yuki; Ando, Masashi; Tsukamasa, Yasuyuki; Takahata, Muneaki

    2015-09-01

    OM-X® is a hand-made and naturally manufactured probiotic supplement. This fermented food product is made from vegetables, fruits, seaweeds and mushrooms, using 12 strains of lactic acid bacteria and bifidobacteria. OM-X® is also known to have beneficial health properties, and some of its components show effects on antigen (Ag)-stimulated degranulation activity, indicating that OM-X® may be useful in the treatment of allergy responses and symptoms. In this study, we evaluated the inhibitory effects of OM-X® on Ag-stimulated degranulation in rat basophilic leukemia RBL-2H3 cells, clarified the underlying mechanisms, and determined the active compounds in OM-X® for suppression of degranulation. Treatment with OM-X® gradually suppressed Ag-stimulated degranulation throughout the maturation period. OM-X® also gradually produced melanoidins by lactic acid bacterial fermentation during the maturation process. There was a high correlation between the suppression levels of Ag-stimulated degranulation and the browning of OM-X®. Furthermore, the inhibition of Ag-stimulated degranulation by OM-X® was found to be partially due to the direct inactivation of NADPH oxidase. To elucidate the in vivo effects of OM- X®, type I allergy model mice were orally administered with OM-X®, and the passive cutaneous anaphylaxis (PCA) reaction was measured. OM-X® intake remarkably suppressed the PCA reaction. Taken together, our findings suggest that OMX® could be a beneficial food to ameliorate allergic reactions.

  15. Binding of monoclonal antibody AA4 to gangliosides on rat basophilic leukemia cells produces changes similar to those seen with Fc epsilon receptor activation

    PubMed Central

    1992-01-01

    The mAb AA4 binds to novel derivatives of the ganglioside Gd1b on rat basophilic leukemia (RBL-2H3) cells. Some of the gangliosides are located close to the high affinity IgE receptor (Fc epsilon RI), and binding of mAb AA4 inhibits Fc epsilon RI-mediated histamine release. In the present study, mAb AA4 was found to bind exclusively to mast cells in all rat tissues examined. In vitro, within 1 min of mAb AA4 binding, the cells underwent striking morphologic changes. They lost their normal spindle shaped appearance, increased their ruffling, and spread over the surface of the culture dish. These changes were accompanied by a redistribution of the cytoskeletal elements, actin, tubulin, and vimentin, but only the actin was associated with the membrane ruffles. Binding of mAb AA4 also induces a rise in intracellular calcium, stimulates phosphatidyl inositol breakdown, and activates PKC. However, the extent of these changes was less than that observed when the cells were stimulated with antigen or antibody directed against the Fc epsilon RI. None of these changes associated with mAb AA4 binding were seen when the cells were exposed to nonspecific IgG, IgE, or four other anti-cell surface antibodies, nor were the changes induced by binding mAb AA4 at 4 degrees C or in the absence of extracellular calcium. Although mAb AA4 does not stimulate histamine release, it enhances the effect of the calcium ionophore A23187 mediated release. The morphological and biochemical effects produced by mAb AA4 are similar to those seen following activation of the cell through the IgE receptor. Therefore, the surface gangliosides which bind mAb AA4 may function in modulating secretory events. PMID:1370498

  16. Direct interaction of Syk and Lyn protein tyrosine kinases in rat basophilic leukemia cells activated via type I Fc epsilon receptors.

    PubMed

    Amoui, M; Dráberová, L; Tolar, P; Dráber, P

    1997-01-01

    Activation of rat mast cells through the receptor with high affinity for IgE (Fc epsilonRI) requires a complex set of interactions involving transmembrane subunits of the Fc epsilonRI and two classes of nonreceptor protein tyrosine kinase (PTK). the Src family PTK p53/p56(lyn) (Lyn) and the Syk/ZAP-family PTK p72(syk) (Syk). Early activation events involve increased activity of Lyn and Syk kinases and their translocation into membrane domains containing aggregated Fc epsilonRI, but the molecular mechanisms responsible for these changes have remained largely unclear. To determine the role of Fc epsilonRI subunits in this process, we have analyzed Syk- and Lyn-associated proteins in activated rat basophilic leukemia (RBL) cells and their variants deficient in the expression of Fc epsilonRI beta or gamma subunits. Sepharose 4B gel chromatography of postnuclear supernatants from Nonidet-P40-solubilized antigen (Ag)- or pervanadate-activated RBL cells revealed extensive changes in the size of complexes formed by Lyn and Syk kinases and other cellular components. A fusion protein containing Src homology 2 (SH2) and SH3 domains of Lyn bound Syk from lysates of nonactivated RBL cells; an increased binding was observed when lysates from Ag- or pervanadate-activated cells were used. A similar amount of Syk was bound when lysates from pervanadate-activated variant cells deficient in the expression of Fc epsilonRI beta or gamma subunits were used, suggesting that Fc epsilonRI does not function as the only intermediate in the formation of the Syk-Lyn complexes. Further experiments have indicated that Syk-Lyn interactions occur in Ag-activated RBL cells under in vivo conditions and that these interactions could involve direct binding of the Lyn SH2 domain with phosphorylated tyrosine of Syk. The physical association of Lyn and Syk during mast-like cell activation supports the recently proposed functional cooperation of these two tyrosine kinases in Fc epsilonRI signaling.

  17. Use of a rat basophil leukemia (RBL) cell-based immunological assay for allergen identification, clinical diagnosis of allergy, and identification of anti-allergy agents for use in immunotherapy.

    PubMed

    Sun, Na; Zhou, Cui; Zhou, Xin; Sun, Lu; Che, Huilian

    2015-01-01

    Food allergy is an important public health problem that affects an estimated 8% of young children and 2% of adults. With an increasing interest in genetically-engineered foods, there is a growing need for development of sensitive and specific tests to evaluate potential allergenicity of foods and novel proteins as well as to determine allergic responses to ensure consumer safety. This review covers progress made in the field of development of cell models, specifically that involving a rat basophil leukemia (RBL) cell-based immunoassay, for use in allergen identification, diagnosis, and immunotherapy. The RBL assay has been extensively employed for determining biologically relevant cross-reactivities of food proteins, assessing the effect of processing on the allergenicity of food proteins, diagnosing allergic responses to whole-food products, and identifying anti-allergy food compounds. From the review of the literature, one might conclude the RBL cell-based assay is a better test system when compared to wild-type mast cell and basophil model systems for use in allergen identification, diagnosis, and analyses of potential immunotherapeutics. However, it is important to emphasize that this assay will only be able to identify those allergens to which the human has already been exposed, but will not identify a truly novel allergen, i.e. one that has never been encountered as in its preferred (humanized) configuration.

  18. Proposed diagnostic criteria and classification of basophilic leukemias and related disorders.

    PubMed

    Valent, P; Sotlar, K; Blatt, K; Hartmann, K; Reiter, A; Sadovnik, I; Sperr, W R; Bettelheim, P; Akin, C; Bauer, K; George, T I; Hadzijusufovic, E; Wolf, D; Gotlib, J; Mahon, F-X; Metcalfe, D D; Horny, H-P; Arock, M

    2017-04-01

    Basophils form a distinct cell lineage within the hematopoietic cell family. In various myeloid neoplasms, including chronic myeloid leukemia, basophilia is frequently seen. Acute and chronic basophilic leukemias, albeit rare, have also been described. However, no generally accepted criteria and classification of basophilic leukemias have been presented to date. To address this unmet need, a series of Working Conferences and other meetings were organized between March 2015 and March 2016. The current article provides a summary of consensus statements from these meetings, together with proposed criteria to delineate acute basophilic leukemia (ABL) from chronic basophilic leukemia (CBL) and primary forms of the disease where no preceding myeloid malignancy is detected, from the more common 'secondary' variants. Moreover, the term hyperbasophilia (HB) is proposed for cases with a persistent peripheral basophil count ⩾1000 per μl of blood. This condition, HB, is highly indicative of the presence of an underlying myeloid neoplasm. Therefore, HB is an important checkpoint in the diagnostic algorithm and requires a detailed hematologic investigation. In these patients, an underlying myeloid malignancy is often found and is then labeled with the appendix -baso, whereas primary cases of ABL or CBL are very rare. The criteria and classification proposed in this article should facilitate the diagnosis and management of patients with unexplained basophilia and basophil neoplasms in routine practice, and in clinical studies.

  19. Mechanism of allergic cross-reactions--II. Cross-stimulation, by chemically unrelated ligands, of rat basophilic leukemia cells sensitized with an anti-DNP IgE antibody.

    PubMed

    Varga, J M; Kalchschmid, G; Klein, G F; Fritsch, P

    1991-06-01

    Serotonin release from rat basophilic leukemia (RBL) cells, sensitized with a DNP-binding monoclonal IgE, was stimulated with solid surface (polystyrene)-bound DNP-amino acids. The stimulatory potency of DNP-amino acids was dependent on the structure of amino acid attached to DNP. Generally, DNP-amino acids with high affinities to the sensitizing IgE (I(50) less than 10 microM) were stimulatory in polystyrene-bound form; DNP-amino acids with lower affinities (Pro, Cys, Trp), and aliphatic aromatic DNP-amino acid derivatives were inactive. In addition to structural analogues of DNP, lymecycline, that is chemically unrelated to DNP but was found to have high affinity to IgE(aDNP), was also stimulatory in this system. This drug, and various quinones (e.g. acenaphthene-quinone) in BSA-conjugated forms also stimulated serotonin release from RBL cells sensitized with IgE(aDNP). These studies suggest that (1) There is a threshold of intrinsic ligand binding affinities at approximately I(50) = 10-100 microM; ligands with lower affinities do not stimulate mediator release even if they are presented in multivalent forms; (2) The above affinity threshold for mediator cell stimulation is valid for various ligands, irrespective of their chemical similarity to the immunogen; (3) Multispecific stimulation of mediator release may contribute to the frequently observed allergic cross-reactions, false positive tests for allergies, and anaphylactic reactions to drugs upon first exposure.

  20. Acute myeloid leukemia with basophilic differentiation in a 3-year-old Standardbred gelding

    PubMed Central

    Furness, Mary Catherine; Setlakwe, Emile; Sallaway, John; Wood, Darren; Fromstein, Jordan; Arroyo, Luis G.

    2016-01-01

    A 3-year-old Standardbred gelding with a history of pyrexia, persistent hemorrhage from the oral cavity, and a large, soft swelling at the junction of the caudal aspect of the mandibular rami and proximal neck was evaluated. The horse had neutropenia and anemia, with atypical granulated cells in a blood smear. Additional tests confirmed acute myeloid leukemia with basophilic differentiation, which has been reported in humans, cats, dogs, and cattle but not horses. PMID:27708445

  1. Acute myeloid leukemia with basophilic differentiation in a 3-year-old Standardbred gelding.

    PubMed

    Furness, Mary Catherine; Setlakwe, Emile; Sallaway, John; Wood, Darren; Fromstein, Jordan; Arroyo, Luis G

    2016-10-01

    A 3-year-old Standardbred gelding with a history of pyrexia, persistent hemorrhage from the oral cavity, and a large, soft swelling at the junction of the caudal aspect of the mandibular rami and proximal neck was evaluated. The horse had neutropenia and anemia, with atypical granulated cells in a blood smear. Additional tests confirmed acute myeloid leukemia with basophilic differentiation, which has been reported in humans, cats, dogs, and cattle but not horses.

  2. A case of basophilic leukemia bearing simultaneous translocations t(8;21) and t(9;22).

    PubMed

    Xue, Y Q; Guo, Y; Lu, D R; Gu, J; Lu, D W; Gong, J X; Wang, M H; Zhu, W Y; Lin, B J

    1991-02-01

    We report a case of basophilic leukemia with simultaneous translocations of t(8;21) and t(9;22). The patient's clinical and hematologic findings were characteristic only of t(9;22) but not of t(8;21). This unusual cytogenetic phenomenon raises a challenge to the current concepts of primary chromosomal abnormalities in cancer.

  3. [Basophil CD63 expression in the blood of the anaphylactic shock rat].

    PubMed

    Jing, Li-xia; Guo, Xiang-jie; Jin, Qian-qian; Huang, Miao-miao; Gao, Cai-rong

    2012-06-01

    To explore the value of flow cytometry in anaphylactic shock diagnosis by CD63 expression being detected using flow cytometry to conform the activation of basophils. Sixteen rats were randomly divided into two groups: control group and anaphylactic shock group. The model of anaphylactic shock rat with ovalbumin injection was established. CD63, CD45 and CD203c antibody combination, flow cytometry was employed to detected blood basophil CD63 expression. Immunofluorescence method was employed to observe the CD63 immunofluorescence staining in the rat lung tissue. (1) Pure basophils were obtained by CD45 and CD203c gating. (2) The percentages of basophils CD63 were (17.34 +/- 2.04)% and (1.52 +/- 0.35)% in the experimental and control group, respectively. The differences between two groups were statistically significant (P < 0.01). (3) Compared with the control group, the expression of CD63 in basophils increased in anaphylactic shock lung tissue. The detection of CD63 by flow cytometry could be the supplement of vivo allergic reactions and have good clinical value.

  4. Quantitative relationships between aggregation of IgE receptors, generation of intracellular signals, and histamine secretion in rat basophilic leukemia (2H3) cells. Enhanced responses with heavy water

    SciTech Connect

    Maeyama, K.; Hohman, R.J.; Metzger, H.; Beaven, M.A.

    1986-02-25

    RBL-2H3 cells (a tumor analog of rat mast cells) have plasma-membrane receptors that bind immunoglobulin E, which when aggregated, initiate degranulation. As in other systems, secretion is preceeded by enhanced hydrolysis of inositol phospholipids and by a rise in intracellular Ca2+. Unlike the responses of many other cells, however, both of these earlier events require extracellular Ca2+. The relationship of these events to each other and to the subsequent secretory process is thus unclear. By exposing cells to covalent oligomers of IgE one can demonstrate substantial increases in secretion of histamine by increasing the concentration and size of the oligomers or by using heavy water (D2O) in the medium. We have used such maneuvers to examine the quantitative relationships between aggregation of the receptors and the breakdown of inositol phospholipids, the increase in cytosolic Ca2+ and secretion. Our principal findings were: all treatments that increased secretion, correspondingly increased the changes that precede degranulation. These early events correlated with the degree of aggregation of the receptors even when the stimulatory conditions resulted in maximal secretion. Although the results were insufficient to prove that the hydrolysis of inositol phospholipids is required for the rise in cytosolic Ca2+, the studies with D2O and other observations supported this view. Since a plasma-membrane ion channel for Ca2+ has been implicated in the IgE-mediated rise in cytosolic Ca2+ in RBL 2H3 cells, this in turn suggests a heretofore undescribed role for hydrolysis of inositol phospholipids.

  5. Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3) cells.

    PubMed

    Hasan, Samer; Al Ali, Hussein; Al-Qubaisi, Mothanna; Zobir Hussein, Mohd; Ismail, Maznah; Zainal, Zulkarnain; Nazrul Hakim, Muhammad

    2012-01-01

    A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite "CETN," had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC₅₀ for CETN and ZLH are 617 and 670 μg/mL, respectively.

  6. Controlled-release formulation of antihistamine based on cetirizine zinc-layered hydroxide nanocomposites and its effect on histamine release from basophilic leukemia (RBL-2H3) cells

    PubMed Central

    Hasan, Samer; Ali, Hussein Al; Al-Qubaisi, Mothanna; Hussein, Mohd Zobir; Ismail, Maznah; Zainal, Zulkarnain; Hakim, Muhammad Nazrul

    2012-01-01

    A controlled-release formulation of an antihistamine, cetirizine, was synthesized using zinc-layered hydroxide as the host and cetirizine as the guest. The resulting well-ordered nanolayered structure, a cetirizine nanocomposite “CETN,” had a basal spacing of 33.9 Å, averaged from six harmonics observed from X-ray diffraction. The guest, cetirizine, was arranged in a horizontal bilayer between the zinc-layered hydroxide (ZLH) inorganic interlayers. Fourier transform infrared spectroscopy studies indicated that the intercalation takes place without major change in the structure of the guest and that the thermal stability of the guest in the nanocomposites is markedly enhanced. The loading of the guest in the nanocomposites was estimated to be about 49.4% (w/w). The release study showed that about 96% of the guest could be released in 80 hours by phosphate buffer solution at pH 7.4 compared with about 97% in 73 hours at pH 4.8. It was found that release was governed by pseudo-second order kinetics. Release of histamine from rat basophilic leukemia cells was found to be more sensitive to the intercalated cetirizine in the CETN compared with its free counterpart, with inhibition of 56% and 29%, respectively, at 62.5 ng/mL. The cytotoxicity assay toward Chang liver cells line show the IC50 for CETN and ZLH are 617 and 670 μg/mL, respectively. PMID:22848164

  7. Effects of malathion metabolites on degranulation of and mediator release by human and rat basophilic cells.

    PubMed

    Xiong, S; Rodgers, K

    1997-06-06

    In the present study, the effects of malathion and malathion derivatives on histamine and beta-hexosaminidase release by RBL-1 cells, rat peritoneal mast cells (RPMC), and human peripheral blood basophils (HPBB) and cutaneous mast calls were examined. One hour of incubation of RBL-1 cells with all organophosphate compounds tested, except for malathion and malathion monoacid, led to an increase in histamine release. beta-Hexosaminidase, an enzyme released by basophilic cells and a biochemical marker of degranulation, was not released from RBL-1 cells after 1 h of exposure to organophosphate compounds. Within 4 h, all compounds tested increased the release of histamine and beta-hexosaminidase. Longer exposures led to a decrease in the concentration of the compound that was required to cause mediator release. Exposure of RPMC to organophosphate compounds, with the exception of malathion monoacid and malathion (30 min) or malathion monoacid (1 h), led to the release of histamine, but not beta-hexosaminidase. Incubation of HPBB with malaoxon (51.4 +/- 2.8% total histamine released), malathion diacid (25.7 +/- 2.9%), beta-malathion monoacid (31.4 +/- 2.8%), and isomalathion (57.1 +/- 17.1%) for 1 h led to the release of histamine. Only malaoxon and isomalathion caused beta-hexosaminidase release from HPBB after a 1-h incubation. Incubation of cutaneous mast cells with malaoxon and beta-monoacid for 4 h led to increased release of histamine and beta-hexosaminidase at levels comparable to compound 48/80. These data suggest that malathion metabolites can cause rapid release of histamine from basophilic cells from a variety of origins and species. With prolonged incubation, malathion itself caused the release of mast-cell mediators, suggesting that the cells may be capable of metabolizing malathion. These data also indicate a disparity between the release kinetics of two different mast-cell mediators contained in granules by organophosphates, and that there are different

  8. Human Lactobacillus Strains from the Intestine can Suppress IgE-Mediated Degranulation of Rat Basophilic Leukaemia (RBL-2H3) Cells

    PubMed Central

    Harata, Gaku; He, Fang; Takahashi, Kyoko; Hosono, Akira; Miyazawa, Kenji; Yoda, Kazutoyo; Hiramatsu, Masaru; Kaminogawa, Shuichi

    2016-01-01

    Mast cells play a critical role in immunoglobulin E (IgE)-mediated allergic diseases, and the degranulation of mast cells is important in the pathogenesis of these diseases. A disturbance of the intestinal microflora, especially of endogenous lactic acid bacteria, might be a contributing factor for IgE-mediated allergic diseases. Additional knowledge regarding the interaction of human intestinal Lactobacilli with mast cells is still necessary. Twenty-three strains of Lactobacilli, including commercial and reference strains and strains from the human intestine, were tested for their ability to regulate degranulation of cells from rat basophilic leukemia RBL-2H3 cells (RBL-2H3) in vitro based on a β-hexosaminidase release assay. Each of the tested Lactobacilli characteristically suppressed IgE-mediated degranulation of RBL-2H3 cells, and Lactobacillus GG showed the strongest inhibitory effect on the cells. Furthermore, the bacteria isolated from the human intestine significantly suppressed degranulation of RBL-2H3 cellsin comparison with the reference strains. These results suggest that Lactobacilli, particularly those from the human intestine, can affect the activation of mast cells in a strain-dependent manner. Further study should be conducted to analyse the understanding mechanism. PMID:27801804

  9. The GIT-PIX complexes regulate the chemotactic response of rat basophilic leukaemia cells.

    PubMed

    Gavina, Manuela; Za, Lorena; Molteni, Raffaella; Pardi, Ruggero; de Curtis, Ivan

    2010-01-14

    Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. The GIT-PIX protein complexes are involved in the regulation of cell motility and adhesion and in the endocytic traffic of members of the family of G-protein-coupled receptors. We have investigated the function of the endogenous GIT complexes in the regulation of cell motility stimulated by fMLP (formyl-Met-Leu-Phe) peptide, in a rat basophilic leukaemia RBL-2H3 cell line stably expressing an HA (haemagglutinin)-tagged receptor for the fMLP peptide. Our analysis shows that RBL cells stably transfected with the chemoattractant receptor expressed both GIT1-PIX and GIT2-PIX endogenous complexes. We have used silencing of the different members of the complex by small interfering RNAs to study the effects on a number of events linked to agonist-induced cell migration. We found that cell adhesion was not affected by depletion of any of the proteins of the GIT complex, whereas agonist-enhanced cell spreading was inhibited. Analysis of agonist-stimulated haptotactic cell migration indicated a specific positive effect of GIT1 depletion on trans-well migration. The internalization of the formyl-peptide receptor was also inhibited by depletion of GIT1 and GIT2. The effects of the GIT complexes on trafficking of the receptors was confirmed by an antibody-enhanced agonist-induced internalization assay, showing that depletion of PIX, GIT1 or GIT2 protein caused decreased perinuclear accumulation of internalized receptors. Our results show that endogenous GIT complexes are involved in the regulation of chemoattractant-induced cell motility and receptor trafficking, and support previous findings indicating an important function of the GIT complexes in the regulation of different G-protein-coupled receptors. Our results also indicate that endogenous GIT1 and GIT2 regulate distinct subsets of agonist-induced responses and suggest a possible functional link between the

  10. The GIT–PIX complexes regulate the chemotactic response of rat basophilic leukaemia cells

    PubMed Central

    Gavina, Manuela; Za, Lorena; Molteni, Raffaella; Pardi, Ruggero; Curtis, Ivan de

    2009-01-01

    Background information. Cell motility entails the reorganization of the cytoskeleton and membrane trafficking for effective protrusion. The GIT–PIX protein complexes are involved in the regulation of cell motility and adhesion and in the endocytic traffic of members of the family of G-protein-coupled receptors. We have investigated the function of the endogenous GIT complexes in the regulation of cell motility stimulated by fMLP (formyl-Met-Leu-Phe) peptide, in a rat basophilic leukaemia RBL-2H3 cell line stably expressing an HA (haemagglutinin)-tagged receptor for the fMLP peptide. Results. Our analysis shows that RBL cells stably transfected with the chemoattractant receptor expressed both GIT1–PIX and GIT2–PIX endogenous complexes. We have used silencing of the different members of the complex by small interfering RNAs to study the effects on a number of events linked to agonist-induced cell migration. We found that cell adhesion was not affected by depletion of any of the proteins of the GIT complex, whereas agonist-enhanced cell spreading was inhibited. Analysis of agonist-stimulated haptotactic cell migration indicated a specific positive effect of GIT1 depletion on trans-well migration. The internalization of the formyl-peptide receptor was also inhibited by depletion of GIT1 and GIT2. The effects of the GIT complexes on trafficking of the receptors was confirmed by an antibody-enhanced agonist-induced internalization assay, showing that depletion of PIX, GIT1 or GIT2 protein caused decreased perinuclear accumulation of internalized receptors. Conclusions. Our results show that endogenous GIT complexes are involved in the regulation of chemoattractant-induced cell motility and receptor trafficking, and support previous findings indicating an important function of the GIT complexes in the regulation of different G-protein-coupled receptors. Our results also indicate that endogenous GIT1 and GIT2 regulate distinct subsets of agonist-induced responses and

  11. Rat hepatocarcinogenesis induced by N-nitrosodiethylamine and N-nitrosomorpholine continuously administered at low doses. From basophilic areas of hepatocytes to hepatocellular tumors.

    PubMed Central

    Cortinovis, C.; Klimek, F.; Nogueira, E.

    1991-01-01

    The development of hepatocellular tumors was investigated with histological, histochemical, and morphometrical methods in male Sprague-Dawley rats continuously administered N-nitrosodiethylamine (DEN) or N-nitrosomorpholine (NNM) in the drinking water at low doses (0.5 mg DEN/100 ml; 1 mg NNM/100 ml). Groups of control, DEN-, and NNM-treated rats were investigated at 5-week intervals. Similar results were obtained in DEN- and NNM-treated rats. Two types of areas composed of basophilic or glycogenotic hepatocytes were observed preceding the appearance of hepatocellular adenomas and carcinomas. Besides their cytologic differences, the basophilic and glycogenotic areas induced displayed distinct histochemical features. Both types of areas were detected simultaneously and increased in parallel with time to a similar incidence, but basophilic areas reached larger sizes than the glycogenotic ones. Furthermore, each type of area, which clustered around and along efferent veins, was differently linked to tumorigenesis. Basophilic areas frequently developed into basophilic adenomas and trabecular carcinomas through a characteristic sequence. Early basophilic areas consisted of hepatocytes with lamellar cytoplasmic hyperbasophilia and exhibited the normal laminar liver structure. With time, an increasing number of basophilic areas also contained hepatocytes with powdered diffuse hyperbasophilia, which frequently were arranged in thick trabeculae, showed abundant mitotic figures, and invaded efferent veins. Neither such signs of malignancy nor conversion into basophilic areas or tumors could be established for areas of clear and acidophilic glycogenotic hepatocytes. However, a few small glycogenotic adenomas probably developed from glycogenotic areas. Our data thus underline the central role of basophilic areas for hepatocarcinogenesis. Moreover, taking into account the data from other experiments, it seems likely that although glycogenotic areas may be associated with the

  12. Isolation and characterization of lipid rafts with different properties from RBL-2H3 (rat basophilic leukaemia) cells.

    PubMed Central

    Radeva, Galina; Sharom, Frances J

    2004-01-01

    Lipid rafts are plasma-membrane microdomains that are enriched in certain lipids (sphingolipids, glycosphingolipids and cholesterol), as well as in lipid-modified proteins. Rafts appear to exist in the liquid-ordered phase, which contributes to their partitioning from the surrounding liquid-disordered glycerophospholipid environment. DRM (detergent-resistant membrane) fractions isolated from cells are believed to represent coalesced lipid rafts. We have employed extraction using two different non-ionic detergents, Brij-96 and Triton X-100, to isolate detergent-resistant lipid rafts from rat basophilic leukaemia cell line RBL-2H3, and compared their properties with each other and with plasma-membrane vesicles. DRM fractions were isolated as sealed unilamellar vesicles of similar size (135-170 nm diameter), using either sucrose-density-gradient sedimentation or gel-filtration chromatography. Lipid rafts isolated using Brij-96 and Triton X-100 differed in density, protein content and the distribution between high- and low-density fractions of the known raft constituents, Thy-1, and the non-receptor protein tyrosine kinases, Yes and Lyn. Lyn was found in the raft microdomains in predominantly phosphorylated form. The level of enrichment of the protein constituents of the isolated lipid rafts seemed to depend on the ratio of cell lipid/protein to detergent. As indicated by reactivity with anti-Thy-1 antibodies, lipid rafts prepared using Brij-96 appeared to consist of vesicles with primarily right-side-out orientation. Both Brij-96 and Triton X-100 appear to isolate detergent-insoluble raft microdomains from the rat basophilic leukaemia cell line RBL-2H3, but the observed differences suggest that either the detergents themselves play a role in determining the physicochemical characteristics of the resulting DRM fractions, or different subsets of rafts are isolated by the two detergents. PMID:14769131

  13. Localization of eosinophil granule major basic protein in human basophils

    PubMed Central

    1983-01-01

    In experiments using an immunofluorescent method to localize human eosinophil granule major basic protein (MBP) in cells and tissues, a small number of cells stained for MBP that subsequently could not be identified as eosinophils. Because the Charcot-Leyden crystal protein, another eosinophil protein, was recently identified in basophils, we tested whether MBP might also be a constituent of blood basophils. Highly purified, eosinophil-free basophil suspensions were prepared using the fluorescence-activated cell sorter (FACS) to sort basophil- containing mononuclear cell preparations stained with fluorescein- conjugated sheep IgG anti-human IgE antibody. Using these FACS-purified basophils, we found that: (a) enrichment for surface IgE-positive cells (greater than 95% basophils) by FACS also enriched for cells staining for MBP by immunofluorescence; (b) MBP appeared to be localized in the histamine-, heparin-containing granules; (c) significant quantities of MBP were measurable by radioimmunoassay (RIA) in freeze-thaw detergent extracts of purified basophils; and (d) RIA dose-response curves for extracts of purified eosinophils and basophils had identical slopes. The MBP content of basophils from normal individuals averaged 140 ng/10(6) cells, whereas purified eosinophils from normal donors and patients with the hyper-eosinophilic syndrome averaged 4,979 and 824 ng/10(6) cells, respectively. MBP was also detected by immunofluorescence and RIA in cells obtained from a patient with basophil leukemia, although the MBP content for basophil leukemia cells was lower than that for normal basophils. We conclude that basophils contain a protein that is immunochemically indistinguishable from eosinophil granule MBP. PMID:6350526

  14. Cinnamaldehyde derivatives inhibit degranulation and inflammatory mediator production in rat basophilic leukemia cells.

    PubMed

    Ahn, Sejin; Kim, Eunhee; Lee, Kooyeon; Lee, Deug-Chan

    2016-09-01

    Mast cells play a critical role in allergic diseases. Therefore, development of new therapeutic agents that suppresses the activation of mast cells may help prevent or treat allergic diseases. Here, we investigated the anti-allergic effects of 4-chloro-cinnamaldehyde and 4-trifluoro-cinnamaldehyde in RBL-2H3 cells. β-Hexosaminidase assays revealed that degranulation of RBL-2H3 cells was decreased following treatment with 60μM 4-chloro-cinnamaldehyde or 4-trifluoro-cinnamaldehyde. Moreover, quantitative real-time reverse transcription polymerase chain reaction showed that the relative expression levels of tumor necrosis factor-α, interleukin-4, and cyclooxygenase-2 mRNAs were decreased in RBL-2H3 cells treated with 4-chloro-cinnamaldehyde and 4-trifluoro-cinnamaldehyde in a concentration-dependent manner. Additionally, 4-chloro-cinnamaldehyde blocked the phosphorylation of MKKs and MAPKs. These data clearly suggested that 4-chloro-cinnamaldehyde and 4-trifluoro-cinnamaldehyde had inhibitory effects on the inflammatory responses of mast cells and may have potential as novel therapeutic agents for the prevention or treatment of allergic diseases.

  15. Macelignan inhibits histamine release and inflammatory mediator production in activated rat basophilic leukemia mast cells.

    PubMed

    Han, Young Sun; Kim, Myung-Suk; Hwang, Jae-Kwan

    2012-10-01

    Type I allergy is characterized by the release of granule-associated mediators, lipid-derived substances, cytokines, and chemokines by activated mast cells. To evaluate the anti-allergic effects of macelignan isolated from Myristica fragrans Houtt., we determined its ability to inhibit calcium (Ca(2+)) influx, degranulation, and inflammatory mediator production in RBL-2 H3 cells stimulated with A23187 and phorbol 12-myristate 13-acetate. Macelignan inhibited Ca(2+) influx and the secretion of β-hexosaminidase, histamine, prostaglandin E(2), and leukotriene C(4); decreased mRNA levels of cyclooxygenase-2, 5-lipoxygenase, interleukin-4 (IL-4), IL-13, and tumor necrosis factor-α; and attenuated phosphorylation of Akt and the mitogen-activated protein kinases extracellular signal-regulated kinase, p38, and c-Jun N-terminal kinase. These results indicate the potential of macelignan as a type I allergy treatment.

  16. Isolation of Human Basophils.

    PubMed

    Schroeder, John T; Bieneman, Anja P

    2016-02-02

    Isolating human basophils from blood has long been hampered by the fact that these granulocytes represent just 1% or less of the circulating leukocyte population. We describe herein laboratory protocols that have been refined over the past ∼25 years that now enable investigators to prepare basophils for use in a variety of assays to assess the in vitro biology of these immune cells, both in IgE -dependent and -independent responses. Copyright © 2016 John Wiley & Sons, Inc.

  17. Erythrocyte survival studies in a rat myelogenous leukemia

    SciTech Connect

    Derelanko, M.J.; Meagher, R.C.; Lobue, J.; Khouri, J.A.; Gordon, A.S.

    1982-11-01

    To determine the extent intrinsic erythrocyte defects and/or extrinsic factors were involved in anemia of rats bearing Shay chloroleukemia (SCL), survival of /sup 3/H-DFP labeled erythrocytes was studied in leukemic and nonleukemic hosts. Red blood cells labeled before induction of leukemia, were rapidly lost from the peripheral circulation of SCL rats in terminal stages of disease. However, labeled erythrocytes from terminal SCL animals displayed normal lifespans when transfused into nonleukemic controls. Thus the anemia of this leukemia probably resulted from extrinsic factors associated with the leukemic process. Hemorrhage appeared to be primarily responsible for the anemia of this disease.

  18. Leukemia

    MedlinePlus

    ... a combination of genetic and environmental factors. How leukemia forms In general, leukemia is thought to occur ... causing the signs and symptoms of leukemia. How leukemia is classified Doctors classify leukemia based on its ...

  19. Leukemia

    MedlinePlus

    ... version of this page please turn Javascript on. Leukemia What Is Leukemia? Leukemia is a cancer of the blood cells. ... diagnosed with leukemia are over 50 years old. Leukemia Starts in Bone Marrow Click for more information ...

  20. Differentiation of human basophils: an overview of recent advances and pending questions.

    PubMed

    Arock, Michel; Schneider, Elke; Boissan, Mathieu; Tricottet, Viviane; Dy, Michel

    2002-04-01

    Basophils are rare, circulating leukocytes derived from hematopoietic CD34+ progenitors. The identification of cytokines promoting their development in vitro has led to substantial advances in understanding their differentiation process. An important role could be assigned to interleukin-3 (IL-3), which supports the maturation of hematopoietic progenitors into basophils in vitro and in vivo. In contrast to other myeloid lineages, a specific basophil growth factor has not yet been discovered. Furthermore, it is still unclear whether basophils possess a lineage-restricted progenitor or whether they share a common ancestor with mast cells (MC), eosinophils, or even megakaryocytes. Partial answers to these questions could be provided using in vitro culture systems or taking advantage of hematological disorders, such as chronic and acute myeloid leukemia (CML and AML), some myelodysplastic syndromes, and the very rare acute basophilic leukemia in which basophilic differentiation occurs.

  1. Human basophils express CD22 without expression of CD19.

    PubMed

    Han, K; Kim, Y; Lee, J; Lim, J; Lee, K Y; Kang, C S; Kim, W I; Kim, B K; Shim, S I; Kim, S M

    1999-11-01

    Even modern automatic cell counters cannot count basophils precisely. Therefore, we need a rapid, accurate, precise, and easy method for counting basophils. Using flow cytometry, basophils (CD22+/CD19-) and B cells (CD22+/CD19+) were counted. Within a large lymphocyte light scatter gate, % basophils (G%baso) and % B cells (G%B) were determined from the total count. Another method of analysis was to make two regions (R1 for basophils and R2 for B cells) and to determine in those the % basophils (R1%baso) and % B cells (R2%B) without gating. The flow cytometric basophil counts of the blood of 21 normal controls and 43 chronic myelogenous leukemia (CML) patients were compared with manual basophil count (Ma%baso) and basophil count by Coulter electronic cell counter (Hialeah, FL) (Auto%baso). CD22+/CD19- cells were sorted by a FACSCalibur (Becton Dickinson, San Jose, CA). The G%baso of all samples was 4.66 +/- 5.35%, and R1%baso was 4.23 +/- 4.88%, and they were well-correlated (r = 0.996, P < 0.001). The G%B of all samples was 1.55 +/- 1.68%, and R2%B was 1.59 +/- 1.67%, and they were also well-correlated (r = 0.993, P < 0.001). Their correlation was better in normal controls than in CML. G%baso was well-correlated to Ma%baso (r = 0.827) and Auto%baso (r = 0.806), and R1%baso was well-correlated to Ma%baso (r = 0.831) but showed poor correlation to Auto%baso (r = 0.734). Auto%baso revealed the poorest correlation to Ma%baso (r = 0.692). The sorted CD22+/CD19- cells were all basophils (99.48 +/- 0.30%), and they revealed CD13, CD33, and dim CD45 expression, whereas CD3, CD14, CD16, and HLA-DR were not detected on them. We discovered a specific marker combination to identify basophils (CD22+/CD19-), and we suggest that flow cytometric analysis using these markers is an easy, reliable, and accurate method of basophil counting. Copyright 1999 Wiley-Liss, Inc.

  2. Inverse relationship of tumors and mononuclear cell leukemia infiltration in the lungs of F344 rats

    SciTech Connect

    Lundgren, D.L.; Griffith, W.C.; Hahn, F.F.

    1995-12-01

    In 1970 and F344 rat, along with the B6C3F{sub 1} mouse, were selected as the standard rodents for the National Cancer Institute Carcinogenic Bioassay program for studies of potentially carcinogenic chemicals. The F344 rat has also been used in a variety of other carcinogenesis studies, including numerous studies at ITRI. A major concern to be considered in evaluating carcinogenic bioassay studies using the F344 rat is the relatively high background incidence of mononuclear cell leukemia (MCL) (also referred to as large granular lymphocytic leukemia, Fischer rat leukemia, or monocytic leukemia). Incidences of MCL ranging from 10 to 72% in male F344 rats to 6 to 31% in female F344 rats have been reported. Gaining the understanding of the mechanisms involved in the negative correlations noted should enhance our understanding of the mechanisms involved in the development of lung cancer.

  3. Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-23

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  5. Substantial depletion of the intracellular Ca2+ stores is required for macroscopic activation of the Ca2+ release-activated Ca2+ current in rat basophilic leukaemia cells

    PubMed Central

    Fierro, Leonardo; Parekh, Anant B

    2000-01-01

    Tight-seal whole-cell patch clamp experiments were performed to examine the ability of different intracellular Ca2+ mobilising agents to activate the Ca2+ release-activated Ca2+ current (ICRAC) in rat basophilic leukaemia (RBL-1) cells under conditions of weak cytoplasmic Ca2+ buffering. Dialysis with a maximal concentration of inositol 1,4,5-trisphosphate (IP3) routinely failed to activate macroscopic ICRAC in low buffer (0.1 mM EGTA, BAPTA or dimethyl BAPTA), whereas it activated the current to its maximal extent in high buffer (10 mM EGTA). Dialysis with a poorly metabolisable analogue of IP3, with ionomycin, or with IP3 and ionomycin all failed to generate macroscopic ICRAC in low Ca2+ buffering conditions. Dialysis with the sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) pump blocker thapsigargin was able to activate ICRAC even in the presence of low cytoplasmic Ca2+ buffering, albeit at a slow rate. Exposure to IP3 together with the SERCA blockers thapsigargin, thapsigargicin or cyclopiazonic acid rapidly activated ICRAC in low buffer. Following activation of ICRAC by intracellular dialysis with IP3 and thapsigargin in low buffer, the current was very selective for Ca2+ (apparent KD of 1 mM). Sr2+ and Ba2+ were less effective charge carriers and Na+ was not conducted to any appreciable extent. The ionic selectivity of ICRAC was very similar in low or high intracellular Ca2+ buffer. Fast Ca2+-dependent inactivation of ICRAC occurred at a similar rate and to a similar extent in low or high Ca2+ buffer. Ca2+-dependent inactivation is not the reason why macroscopic ICRAC cannot be seen under conditions of low cytoplasmic Ca2+ buffering. ICRAC could be activated by combining IP3 with thapsigargin, even in the presence of 100 μM Ca2+ and the absence of any exogenous Ca2+ chelator, where ATP and glutamate represented the only Ca2+ buffers in the pipette solution. Our results suggest that a threshold exists within the IP3-sensitive Ca2+ store, below which

  6. Decitabine, Cytarabine, and Daunorubicin Hydrochloride in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-09-04

    Acute Myeloid Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  8. Isolation of a basophilic membrane protein binding the anti-allergic drug cromolyn.

    PubMed Central

    Mazurek, N; Bashkin, P; Pecht, I

    1982-01-01

    The membrane protein component in basophils, responsible for the specific, Ca2+-dependent, binding of the anti-allergic drug cromolyn [disodium cromoglycate, DSCG; the disodium salt of 1,2 bis(2- carboxychromon -5- yloxy )-2-hydroxy propane] was isolated by two procedures based on affinity for the drug. In the first procedure, involving immunoprecipitation, rat basophilic leukemia cells (RBL-2H3), surface labeled by 125I were reacted with a polyvalent conjugate of DSCG and bovine serum albumin and then subjected to solubilization by the non-ionic detergent Nonidet P-40 (NP-40). From these lysates, precipitation was specifically attained by subsequent addition of rabbit anti-DSCG antibodies. In an SDS-polyacrylamide gel electrophoresis (SDS-PAGE), a single radioactive band was observed, having an apparent mol. wt. of 60 000 daltons. Competitive inhibition of the immunoprecipitation in the presence of free drug or excess of EDTA demonstrated the specificity of the isolation. Furthermore, this particular membrane component could not be isolated from several other cell types examined. The second isolation from several other cell types examined. The second isolation procedure employed affinity chromatography on DSCG immobilized on polyacryl- hydrazido agarose beads. The DSCG-binding protein was eluted from the affinity column with either DSCG or with EDTA and also migrated on SDS-PAGE as a single band of 60 000 mol. wt., similar to that obtained by the immunoprecipitation procedure. These and other results suggest that this newly isolated protein is the one responsible for the Ca2+-dependent binding of the drug to the basophil membrane. Images Fig. 1. Fig. 2. Fig. 4. PMID:6821355

  9. Flavopiridol in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia

  10. Tipifarnib and Bortezomib in Treating Patients With Acute Leukemia or Chronic Myelogenous Leukemia in Blast Phase

    ClinicalTrials.gov

    2015-04-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Blastic Phase; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Nonredundant roles of basophils in immunity.

    PubMed

    Karasuyama, Hajime; Mukai, Kaori; Obata, Kazushige; Tsujimura, Yusuke; Wada, Takeshi

    2011-01-01

    Basophils are the rarest granulocytes and represent less than 1% of peripheral blood leukocytes. They are evolutionarily conserved in many animal species, but their functional significance remained an enigma long after their discovery by Paul Ehrlich in 1879. Studies of basophils were hindered by their rarity, by difficulties in identifying them, and by the paucity of useful analytical tools. Because basophils display several characteristics shared by tissue-resident mast cells, they were often considered minor and possibly redundant relatives of mast cells or even blood-circulating precursors of mast cells. However, newly developed tools for their functional analysis, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have fueled basophil research and defined previously unrecognized functions of basophils. We now appreciate that basophils play nonredundant roles in acquired immunity regulation, protective immunity to pathogens, and immunological disorders such as allergy and autoimmunity.

  12. Sorafenib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-08

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  13. [Mast cells and basophils and their disorders].

    PubMed

    Bösiger, J; Fehr, J

    2006-01-01

    This short review gives a brief overview on recent findings about the roles of basophils and mast cells in acquired and innate immunity. We try to give some insight into the methods used to study physiologic functions of mast cells and basophils. We mention variations of circulating basophil numbers as an epiphenomenon of some internal diseases and present an update on mastocytosis.

  14. Hematologic and serum chemical characteristics of mononuclear leukemia in Fischer 344 rats

    SciTech Connect

    Kusewitt, D.F.; Hahn, F.F.; Pickrell, J.A.

    1982-01-01

    Hematologic, serum chemical, and histopathologic studies were performed on 17 aged Fischer 344 rats with mononuclear leukemia. Twelve of the rats had leukemic hemograms, while five had nonleukemic or marginally abnormal differential leukocyte counts. Hematologic findings revealed that all rats were profoundly anemic. Serum chemistry studies confirmed the occurrence of icterus observed clinically, a finding consistent with hemolytic anemia. Alanine aminotransferase and serum alkaline phosphatase values were elevated.

  15. Role for basophils in systemic anaphylaxis.

    PubMed

    Karasuyama, Hajime; Tsujimura, Yusuke; Obata, Kazushige; Mukai, Kaori

    2010-01-01

    For more than 100 years since the discovery of basophils by Paul Ehrlich, the functional significance of this rare leukocyte as compared to mast cells has remained an enigma. Studies on basophils have long been hampered by their rarity (less than 1% of peripheral blood leukocytes) and the lack of useful analytical tools such as model animals deficient only in basophils. Recent studies have now defined previously-unrecognized roles for basophils in both allergic responses and immune regulation, and markedly changed our image of basophils, from a neglected minority to a key player in the immune system. We have recently demonstrated that basophils and mast cells play distinct roles in systemic anaphylaxis in mice. Basophils are dispensable for IgE-mediated systemic anaphylaxis unlike mast cells. Instead, basophils play the major role in IgG-mediated systemic anaphylaxis. In vivo depletion of basophils protects mice from anaphylactic death. Upon capture of IgG-allergen complexes, basophils release platelet-activating factor that increases vascular permeability, leading to anaphylactic shock. Thus, there are two major, distinct pathways to allergen-induced systemic anaphylaxis: one mediated by basophils, IgG and platelet-activating factor, and the other 'classical' pathway mediated by mast cells, IgE and histamine. Copyright 2010 S. Karger AG, Basel.

  16. Cilengitide in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-23

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b)

  17. Purification of basophils from peripheral human blood.

    PubMed

    Falcone, Franco H; Gibbs, Bernhard F

    2014-01-01

    The purification of basophils from peripheral blood has represented a formidable challenge for researchers since they were discovered by Paul Ehrlich in 1879. From the first published attempts in the late 1960s, it took half a century to develop robust protocols able to provide sufficient numbers of pure, functionally unimpaired basophils. The existing protocols for basophil purification exploit those properties of basophils which distinguish them from other cell types such as their localization in blood, density, and the presence or absence of surface markers. Purification techniques have been used in various combinations and variations to achieve a common goal in mind: to obtain a pure population of human basophils in sufficient numbers for downstream studies. The arduous way leading up to the modern protocols is summarized in this historical retrospective. A fast protocol for purification of basophils to near homogeneity is also described.

  18. Anti leukemia activity (Dunning ascitic) of 6-mercaptopurine and its metallo complexes in rats.

    PubMed

    Skinner, S M; Swatzell, J M; Lewis, R W

    1978-01-01

    Six-mercaptopurine and its Pt, Pd and Bi complexes were used at various dosage levels to treat Dunning ascitic leukemia in rats. Significant anticarcinogenic activity was found in all compounds with toxicity apparent at the highest dosage level of all but the platinum compound.

  19. Natural cytotoxic (NC) activity in basophilic cells: mediation by a NC-specific cytotoxic factor

    SciTech Connect

    Okuno, T.; Takagaki, Y.; Pluznik, D.; Djeu, J.Y.

    1986-03-01

    Interleukin 3 (IL3) has recently been shown to be a mast cell/basophil growth factor. Based on the previous observations that IL3-dependent cells are capable of NC activity which are believed to be important in immunosurveillance, the authors attempted to define if the IL3-dependent NC cells were of basophilic origin. To approach this, the authors tested a murine IL3-dependent basophilic cell line and a rat basophilic leukemic cell line against various tumor targets in a 4h or 18h /sup 51/Cr release assay. Both basophilic cell types effectively lysed the NC target, WEHI-164, but not the NK targets, YAC-1, RLM1, RBL5. Moreover, triggering of the basophils by incubation at 37C with IgE-anti-IgE or IgE with specific antigen or by direct binding to anti-IgE receptor antibodies enhanced NC activity and at the same time induced the release of a soluble cytotoxic factor (CF). The CF lysed only WEHI but not YAC-1, RLM1 or RBL5 tumor cells, distinguishing it from NKCF. The release of the NCCF was dependent on the dose of the triggering agents, required extracellular Ca/sup + +/, and was detected within 15 min of triggering. It has a MW of 43,000 as determined by gel filtration. Basophils, therefore, are not only involved in inflammatory responses but also in tumor immunity, via the NC effector mechanism.

  20. Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-13

    Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  1. Tipifarnib in Treating Older Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-03-22

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Cellular Diagnosis, Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  2. Large granular lymphocytic (LGL) leukemia in rats exposed to intermittent 60 Hz magnetic fields.

    PubMed

    Anderson, L E; Morris, J E; Miller, D L; Rafferty, C N; Ebi, K L; Sasser, L B

    2001-04-01

    An animal model for large granular lymphocytic (LGL) leukemia in male Fischer 344 rats was utilized to determine whether magnetic field exposure can be shown to influence the progression of leukemia. We previously reported that exposure to continuous 60 Hz, 1 mT magnetic fields did not significantly alter the clinical progression of LGL leukemia in young male rats following injection of spleen cells from donor leukemic rats. Results presented here extend those studies with the following objectives: (a) to replicate the previous study of continuous 60 Hz magnetic field exposures, but using fewer LGL cells in the inoculum, and (b) to determine if intermittent 60 Hz magnetic fields can alter the clinical progression of leukemia. Rats were randomly assigned to four treatment groups (18/group) as follows: (1) 1 mT (10 G) continuous field, (2) 1 mT intermittent field (off/on at 3 min intervals), (3) ambient controls ( < 0.1 microT), and (4) positive control (5 Gy whole body irradiation from cobalt-60 four days prior to initiation of exposure). All rats were injected intraperitoneally with 2.2 x 10(6) fresh, viable LGL leukemic spleen cells at the beginning of the study. The fields were activated for 20 h per day, 7 days per week, and all exposure conditions were superimposed over the natural ambient magnetic field. The rats were weighed and palpated for splenomegaly weekly. Splenomegaly developed 9-11 weeks after transplantation of the leukemia cells. Hematological evaluations were performed at 6, 8, 10, 12, 14, and 16 weeks of exposure. Peripheral blood hemoglobin concentration, red blood cells, and packed cell volume declined, and total white blood cells and LGL cells increased dramatically in all treatment groups after onset of leukemia. Although the positive control group showed different body weight curves and developed signs of leukemia earlier than other groups, differences were not detected between exposure groups and ambient controls. Furthermore, there were no

  3. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-07-25

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  4. Basophils: a nonredundant contributor to host immunity.

    PubMed

    Sullivan, Brandon M; Locksley, Richard M

    2009-01-16

    The role of basophils, the rarest of blood granulocytes, in host immunity has been a mystery. Long considered the poor relative of mast cells, basophils have received much recent attention because of the availability of new reagents and models that reveal unique properties of these cells. Basophils are known to have distinct roles in allergic hypersensitivity reactions and in the immune response to intestinal helminthes. In this review, we highlight these advances and summarize our current understanding of the repertoire of functions attributed to these cells. Despite these recent insights, we are likely only beginning to gain a full understanding of how and where these cells lend effector functions to vertebrate immunity. Advances are likely to come only with the development of specific reagents that enable the finer study of basophil lineage and function. Although many fundamental aspects of basophil biology remain unanswered, the prospects remain bright for unmasking new contributions by these unusual cells.

  5. Azacitidine, Mitoxantrone Hydrochloride, and Etoposide in Treating Older Patients With Poor-Prognosis Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  6. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2017-07-10

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  7. Tanespimycin and Cytarabine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, Chronic Myelomonocytic Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  8. Eltrombopag Olamine in Improving Platelet Recovery in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    ClinicalTrials.gov

    2017-07-26

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  9. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  10. Idarubicin, Cytarabine, and Tipifarnib in Treating Patients With Newly Diagnosed Myelodysplastic Syndromes or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-09

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  11. Activation of basophil and mast cell histamine release by eosinophil granule major basic protein

    PubMed Central

    1983-01-01

    Major basic protein (MBP) is a primary constituent of eosinophil granules. In this report, we demonstrate that MBP from human eosinophil granules initiates a nonlytic histamine release from human leukocytes. A direct effect of MBP on basophils was confirmed using purified human basophils. The kinetics of release were similar to those reported for poly-L-arginine, although MBP was less potent than poly-L-arginine of similar molecular weight. Reduction and alkylation of MBP diminished both the potency and efficacy of the molecule. Native MBP also stimulated histamine secretion from purified rat peritoneal mast cells in a manner characteristic of other polycations. These results emphasize the bidirectional nature of the basophil/mast cell-eosinophil regulatory axis. PMID:6854212

  12. Flow cytometric allergy diagnosis: basophil activation techniques.

    PubMed

    Bridts, Chris H; Sabato, Vito; Mertens, Christel; Hagendorens, Margo M; De Clerck, Luc S; Ebo, Didier G

    2014-01-01

    The basis of flow cytometric allergy diagnosis is quantification of changes in expression of basophilic surface membrane markers (Ebo et al., Clin Exp Allergy 34: 332-339, 2004). Upon encountering specific allergens recognized by surface receptor FcεRI-bound IgE, basophils not only secrete and generate quantifiable bioactive mediators but also up-regulate the expression of different markers (e.g., CD63, CD203c) which can be detected by multicolor flow cytometry using specific monoclonal antibodies (Ebo et al., Cytometry B Clin Cytom 74: 201-210, 2008). Here, we describe two flow cytometry-based protocols which allow detection of surface marker activation (Method 1) and changes in intragranular histamine (Method 2), both reflecting different facets of basophil activation.

  13. Chemopreventive and anti-leukemic effects of ethanol extracts of Moringa oleifera leaves on wistar rats bearing benzene induced leukemia.

    PubMed

    Akanni, E O; Adedeji, A L; Adedosu, O T; Olaniran, O I; Oloke, J K

    2014-01-01

    Pharmacological exploitation of natural compounds has continued to lead to development of non-synthetic and non-toxic anticancer agents that are promising at ameliorating the menace of neoplastic diseases such as leukemia. This study is an attempt to determine the chemopreventive and antileukemic activities of ethanol extracts of Moringa oleifera leaves on benzene induced leukemia bearing rats. Leukemia was induced by intravenous injection of 0.2 mL benzene solution 48 hourly for 4 weeks in appropriate rat groups. Ethanol extract of Moringa oleifera (EMO) leaves was administered at 0.2 mL of 100 mg/mL to respective treatment rat groups. A standard antileukemic drug (cyclophosphamide) was also used to treat appropriate rat groups. Clinical examination of liver and spleen with hematological parameters were employed to assess the leukemia burden following analysis of the rat blood samples on Sysmex KX-21N automated instrument. Leukemia induction reflected in severe anemia and a marked leukocytosis over the control/baseline group. Liver and spleen enlargements were also observed in group exposed to benzene carcinogen. The in vivo antioxidative potential of EMO was evaluated using Malondialdehyde (MDA) and reduced glutathione (GSH) levels. The liver MDA and GSH levels obtained in benzene induced leukemic rats treated with EMO compared favorably with those obtained in similar treatments with the standard drug (p< 0.05). The extract demonstrated chemopreventive and anti-leukemic activities as much as the standard anti-leukemic drug (p>0.05) by ameliorating the induced leukemic condition in the affected rat groups owing to its bioactive constituents. This study reveals that the extract might be an active, natural and non-toxic anticancer drug lead.

  14. Eltrombopag Olamine in Treating Patients With Relapsed/Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-04

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia

  15. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-14

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Effect of leukemia inhibitory factor and forskolin on establishment of rat embryonic stem cell lines.

    PubMed

    Hirabayashi, Masumi; Goto, Teppei; Tamura, Chihiro; Sanbo, Makoto; Hara, Hiromasa; Hochi, Shinichi

    2014-03-07

    This study was designed to investigate whether supplementation of 2i medium with leukemia inhibitory factor (LIF) and/or forskolin would support establishment of germline-competent rat embryonic stem (ES) cell lines. Due to the higher likelihood of outgrowth rates, supplementation of forskolin with or without LIF contributed to the higher establishment efficiency of ES cell lines in the WDB strain. Germline transmission competency of the chimeric rats was not influenced by the profile of ES cell lines until their establishment. When the LIF/forskolin-supplemented 2i medium was used, the rat strain used as the blastocyst donor, such as the WI strain, was a possible factor negatively influencing the establishment efficiency of ES cell lines. Once ES cell lines were established, all lines were found to be germline-competent by a progeny test in chimeric rats. In conclusion, both LIF and forskolin are not essential but can play a beneficial role in the establishment of "genuine" rat ES cell lines.

  17. Basophil markers for identification and activation in the indirect basophil activation test by flow cytometry for diagnosis of autoimmune urticaria.

    PubMed

    Kim, Zehwan; Choi, Bong Seok; Kim, Jong Kun; Won, Dong Il

    2016-01-01

    The indirect basophil activation test using flow cytometry is a promising tool for autoimmune urticaria diagnosis. We aimed to identify better donor basophils (from atopic vs. non-atopic donors and interleukin-3 primed vs. unprimed basophils) and improve basophil identification and activation markers (eotaxin CC chemokine receptor-3 [CCR3] vs. CD123 and CD63 vs. CD203c). Donor basophils were obtained from non-atopic and atopic group O donors. Positive control sera were artificially prepared to simulate autoimmune urticaria patients' sera. Patient sera were obtained from nine children with chronic urticaria. Assay sensitivity was compared among each variation by using positive control sera (n=21), applying cutoff values defined from negative control sera (n=20). For basophil identification, a combination of CCR3 and CD123 markers revealed a higher correlation with automated complete blood count (r=0.530) compared with that observed using CD123 (r=0.498) or CCR3 alone (r=0.195). Three activation markers on the atopic donor basophils attained 100% assay sensitivity: CD203c on unprimed basophils, CD63+CD203+ or CD63 alone on primed basophils; however, these markers on the non-atopic donor basophils attained lower assay sensitivity. For basophil identification markers, a combination of CD123 and CCR3 is recommended, while CD123 alone may be used as an alternative. Donor basophils should be obtained from an atopic donor. For basophil activation markers, either CD203c alone on unprimed basophils or CD203c and CD63 on primed basophils are recommended, while CD63 alone on primed basophils may be used as an alternative.

  18. Basophil activation tests: time for a reconsideration.

    PubMed

    Uyttebroek, Astrid P; Sabato, Vito; Faber, Margaretha A; Cop, Nathalie; Bridts, Chris H; Lapeere, Hilde; De Clerck, Luc S; Ebo, Didier G

    2014-10-01

    Challenges in in vitro allergy diagnostics lie in the development of accessible and reliable assays allowing identification of all offending allergens and cross-reactive structures. Flow-assisted analysis and quantification of in vitro activated basophils serves as a diagnostic instrument with increasing applications developed over the years. From the earliest days it was clear that the test could constitute a diagnostic asset in basophil-mediated hypersensitivity. However, utility of the basophil activation test should be reassessed regarding difficulties with preparation, characterization and validation of allergen extracts; availability and the potential of more accessible diagnostics. Today, the added value mainly lies in diagnosis of immediate drug hypersensitivity. Other potential indications are monitoring venom-immunotherapy and follow-up of natural history of food allergies. However, results in these nondiagnostic applications are preliminary. We review the most relevant clinical applications of the basophil activation test. Some personal comments and views about perspectives and challenges about flow-assisted allergy diagnosis are made.

  19. Entinostat and Sorafenib Tosylate in Treating Patients With Advanced or Metastatic Solid Tumors or Refractory or Relapsed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-18

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Myeloid Leukemia; Unspecified Adult Solid Tumor, Protocol Specific

  20. An anthocyanin-rich extract from Hibiscus sabdariffa linnaeus inhibits N-nitrosomethylurea-induced leukemia in rats.

    PubMed

    Tsai, Tsung-Chang; Huang, Hui-Pei; Chang, Yun-Ching; Wang, Chau-Jong

    2014-02-19

    A previous study reported that anthocyanins from roselle (Hibiscus sabdariffa L.) showed significant anticancer activity in human promyelocytic leukemia cells. To explore the antitumor effect of anthocyanin, a roselle bioactive polyphenol in a rat model of chemical-induced leukemia was assayed. Anthocyanin extract of roselle (Hibiscus anthocyanins, HAs) was supplemented in the diet (0.1 and 0.2%). This study was carried out to evaluate the protective effect of HAs on N-nitrosomethylurea (NMU)-induced leukemia of rats. The study employed male Sprague-Dawley rats (n = 48), and leukemia was induced by intravenous injection of 35 mg kg(-1) body weight of NMU dissolved in physiologic saline solution. The rats were divided into four groups (n = 12): control, NMU only, and HAs groups that received different doses of HAs (0.1 and 0.2%) daily, orally, after NMU injection. After 220 days, the animals were killed, and the following parameters were assessed: morphological observation, hematology examination, histopathological assessment, and biochemical assay. When compared with the NMU-only group, HAs significantly prevented loss of organ weight and ameliorated the impairment of morphology, hematology, and histopathology. Treatment with HAs caused reduction in the levels of AST, ALT, uric acid, and MPO. Also, the results showed that oral administration of HAs (0.2%) remarkably inhibited progression of NMU-induced leukemia by approximately 33.3% in rats. This is the first report to demonstrate that the sequential administration of HAs followed by NMU resulted in an antileukemic activity in vivo.

  1. Basophils, cytokines, and the allergic inflammatory response.

    PubMed

    DuBuske, L M

    1996-01-01

    Immediate allergic response has long been recognized to be related to the activation of mast cells by antigen. The role of the mast cells as producers of cytokines, however, has only more recently been extensively studied. The effect of TH2 lymphocytes in the inflammatory process is now well recognized in animal models. The central role of cytokines in the allergic inflammatory response is currently an area of intense clinical investigation. Cytokines influence production, migration, and activation of basophils. A wide array of cytokines is produced by mast cells upon initiation of the immediate allergic response. These cytokines influence a number of other different cells including basophils and eosinophils, and also activate lymphocytes, thus perpetuating allergic inflammation.

  2. Basophil depletion downregulates Schistosoma mansoni egg-induced granuloma formation.

    PubMed

    Anyan, William K; Seki, Takenori; Kumagai, Takashi; Obata-Ninomiya, Kazushige; Furushima-Shimogawara, Rieko; Kwansa-Bentum, Bethel; Akao, Nobuaki; Bosompem, Kwabena M; Boakye, Daniel A; Wilson, Michael D; Karasuyama, Hajime; Ohta, Nobuo

    2013-12-01

    Granuloma formation around parasite eggs during schistosomal infection is considered to be controlled by Th2 cytokines. However, it is still controversial which cell populations are responsible for the host Th2 cytokine-dependent granuloma formation. Basophils have recently attracted attention because of their ability to produce large amounts of IL-4. Therefore, we investigated whether basophils play an essential role in the induction of granuloma formation induced by Schistosoma mansoni eggs. Together with our previous observation that basophil numbers increased markedly in the spleen at 7 weeks postinfection, immunohistochemical staining using anti-mMCP8 monoclonal antibody (mAb) showed basophil infiltration in the granulomatous lesions formed around parasite eggs. To examine the roles of basophils more directly, we treated mice with anti-CD200R3 mAb to deplete basophils. Depletion of basophils resulted in a reduction of basophil number with concomitant downregulation of egg granuloma formation at 7 weeks postinfection. Moreover, we observed a significant reduction in the size of egg granulomas formed in basophil-depleted mice in the pulmonary granuloma model. Taken together, these findings indicated that basophils are essential for S. mansoni egg-induced granuloma formation, and this may serve as a novel therapeutic target in ameliorating the pathology of schistosomiasis.

  3. Hepatic Lesions Caused by Large Granular Lymphocyte Leukemia in Fischer 344 Rats: Similar Morphologic Features and Morphogenesis to Those of Nodular Regenerative Hyperplasia (NRH) in the Human Liver.

    PubMed

    Shiga, Atsushi; Narama, Isao

    2015-08-01

    To characterize the hepatic lesions in Fischer 344 (F344) rats afflicted with large granular lymphocyte (LGL) leukemia, the livers of rats with LGL leukemia at various stages were examined histopathologically and immunohistochemically. The morphologic features in the livers of rats afflicted with LGL leukemia were diffuse, uniform-sized, granular, or micronodular lesions consisting of hepatocytes showing centrilobular atrophy and perilobular hypertrophy (CAPH) without fibrosis. With progression in the stage of the LGL leukemia, the severity of the CAPH of hepatocytes increased resulting in fatty change and/or single-cell necrosis, along with compensatory hyperplasia of the hepatocytes, finally resulting in lesions similar to those seen in nodular regenerative hyperplasia (NRH) in the human liver. The CAPH of hepatocytes was a nonspecific tissue adaptation against ischemia or hypoxemia and/or imbalance in blood supply due to disturbance in the portal circulation and hemolytic anemia induced by the leukemia cells. In addition, direct and/or indirect hepatocellular injuries by leukemia cells were considered to be necessary for the formation of human NRH-like lesions. Morphogenetic investigation of the livers of rats afflicted with LGL leukemia may be helpful to clarify the pathogenesis of NRH in the human liver.

  4. Biological potential of basophilic hepatocellular foci and hepatic adenoma induced by the peroxisome proliferator, Wy-14,643.

    PubMed

    Marsman, D S; Popp, J A

    1994-01-01

    The biological potential of hepatic foci and tumors induced by peroxisome proliferators such as Wy-14,643 has been poorly characterized. In this study, male F-344 rats (n = 20/group/time point) were fed Wy-14,643 (0.1%) for 22, 37 or 52 weeks ('W-22', 'W-37' or 'W-52' respectively). At each time point some rats were killed and additional Wy-14,643-fed rats were switched to basal diet (Wy-14,643/'stopped') for up to 104 weeks (referred to as 'W-22/S', 'W-37/S' and 'W-52/S'). Homogeneous basophilic foci, but not clear cell foci, increased in number and size in W-37 and W-52 rats. In W-37/S rats, clear cell foci replaced basophilic foci as the most frequent phenotype. In serial section overlays, adenosine triphosphatase deficient foci accounted for only 16% of basophilic foci in W-52 rats and 16% of clear cell foci in W-37/S rats at 52 weeks. The replication of basophilic foci of W-37 rats was markedly increased (focal labeling index, FLI = 61.8% versus non-focal labeling index, LI = 11.4%; control LI = 0.8%). Clear cell foci from W-37/S rats at 52 weeks had a FLI of 1.6% (non-focal LI = 0.6%). Hepatocellular adenomas were increased in W-37 (11/20 rats and 0.8 tumors/rat) and W-52 groups (19/20 rats and 2.8 tumors/rat). Prevalence of hepatocellular carcinomas was elevated in W-52 rats (6/20 rats) but not in W-22 or W-37 rats. Following removal of Wy-14,643, prevalence of animals with malignant, metastatic hepatocellular carcinomas in W-52/S rats was similar to the prevalence in W-52 rats. However, Wy-14,643-induced adenomas completely regressed in W-37/S and W-52/S groups. In summary, significant morphological continuity between highly proliferative basophilic foci and hepatocellular tumors was identified, emphasizing the superiority of basophilia as a marker for lesions leading to development of hepatocellular neoplasia in rats fed Wy-14,643. An important biological distinction was noted between regressive hepatic adenomas and progressive hepatocellular carcinomas

  5. Sorafenib in Treating Patients With Refractory or Relapsed Acute Leukemia, Myelodysplastic Syndromes, or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-04-27

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  6. Klinefelter syndrome and acute basophilic leukaemia--case report.

    PubMed

    Ljubić, Nives; Lang, Nada; Skelin, Ika Kardum; Lasan, Ruzica; Dominis, Mara; Perković, Leila; Zupanić-Krmek, Dubraka; Grgurević-Batinica, Anita

    2010-06-01

    Patients with 47, XXY karyotype (Klinefelter syndrome) appear to have increased risk of developing cancer, especially male breast cancer, germ cell tumours and non Hodgkin lymphomas, but rarely acute myeloid leukaemia. We report a patient with acute basophilic leukaemia with 47, XXY karyotype in both the tumour and constitutional cells. Acute basophilic leukaemia is very rare disease comprising less than 1% of all acute myeloid leukaemias. Morphological characteristic of leukaemic blast cells is moderately basophilic cytoplasm containing a variable number of coarse basophilic granules. The most characteristic cytochemical reaction is metachromatic positivity with toluidine blue. Blast are myeloperoxidase negative. Also leukemic blasts express myeloid and monocyte markers. There is no consistent chromosomal abnormality identified in this leukaemia. This is the first reported case of acute basophilic leukaemia in patient with Klinefelter syndrome. In this article the medical history of the patient is given and the possible connection between Klinefelter syndrome and acute myeloid leukaemia is discussed.

  7. Regulation of basophil and mast cell development by transcription factors.

    PubMed

    Sasaki, Haruka; Kurotaki, Daisuke; Tamura, Tomohiko

    2016-04-01

    Basophils and mast cells play important roles in host defense against parasitic infections and allergic responses. Several progenitor populations, either shared or specific, for basophils and/or mast cells have been identified, thus elucidating the developmental pathways of these cells. Multiple transcription factors essential for their development and the relationships between them have been also revealed. For example, IRF8 induces GATA2 expression to promote the generation of both basophils and mast cells. The STAT5-GATA2 axis induces C/EBPα and MITF expression, facilitating the differentiation into basophils and mast cells, respectively. In addition, C/EBPα and MITF mutually suppress each other's expression. This review provides an overview of recent advances in our understanding of how transcription factors regulate the development of basophils and mast cells.

  8. High-Cholesterol Diet Disrupts the Levels of Hormones Derived from Anterior Pituitary Basophilic Cells.

    PubMed

    Yang, J; Zhang, X; Liu, Z; Yuan, Z; Song, Y; Shao, S; Zhou, X; Yan, H; Guan, Q; Gao, L; Zhang, H; Zhao, J

    2016-03-01

    Emerging evidence shows that elevated cholesterol levels are detrimental to health. However, it is unclear whether there is an association between cholesterol and the pituitary. We investigated the effects of a high-cholesterol diet on pituitary hormones using in vivo animal studies and an epidemiological study. In the animal experiments, rats were fed a high-cholesterol or control diet for 28 weeks. In rats fed the high-cholesterol diet, serum levels of thyroid-stimulating hormone (TSH; also known as thyrotrophin), luteinising hormone (LH) and follicle-stimulating hormone (FSH) produced by the basophilic cells of the anterior pituitary were elevated in a time-dependent manner. Among these hormones, TSH was the first to undergo a significant change, whereas adrenocorticotrophic hormone (ACTH), another hormone produced by basophilic cells, was not changed significantly. As the duration of cholesterol feeding increased, cholesterol deposition increased gradually in the pituitary. Histologically, basophilic cells, and especially thyrotrophs and gonadotrophs, showed an obvious increase in cell area, as well as a potential increase in their proportion of total pituitary cells. Expression of the β-subunit of TSH, FSH and LH, which controls hormone specificity and activity, exhibited a corresponding increase. In the epidemiological study, we found a similar elevation of serum TSH, LH and FSH and a decrease in ACTH in patients with hypercholesterolaemia. Significant positive correlations existed between serum total cholesterol and TSH, FSH or LH, even after adjusting for confounding factors. Taken together, the results of the present study suggest that the high-cholesterol diet affected the levels of hormones derived from anterior pituitary basophilic cells. This phenomenon might contribute to the pituitary functional disturbances described in hypercholesterolaemia.

  9. Leukemia Inhibitory Factor in Rat Fetal Lung Development: Expression and Functional Studies

    PubMed Central

    Nogueira-Silva, Cristina; Piairo, Paulina; Carvalho-Dias, Emanuel; Peixoto, Francisca O.; Moura, Rute S.; Correia-Pinto, Jorge

    2012-01-01

    Background Leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) are members of the family of the glycoprotein 130 (gp130)-type cytokines. These cytokines share gp130 as a common signal transducer, which explains why they show some functional redundancy. Recently, it was demonstrated that IL-6 promotes fetal lung branching. Additionally, LIF has been implicated in developmental processes of some branching organs. Thus, in this study LIF expression pattern and its effects on fetal rat lung morphogenesis were assessed. Methodology/Principal Findings LIF and its subunit receptor LIFRα expression levels were evaluated by immunohistochemistry and western blot in fetal rat lungs of different gestational ages, ranging from 13.5 to 21.5 days post-conception. Throughout all gestational ages studied, LIF was constitutively expressed in pulmonary epithelium, whereas LIFRα was first mainly expressed in the mesenchyme, but after pseudoglandular stage it was also observed in epithelial cells. These results point to a LIF epithelium-mesenchyme cross-talk, which is known to be important for lung branching process. Regarding functional studies, fetal lung explants were cultured with increasing doses of LIF or LIF neutralizing antibodies during 4 days. MAPK, AKT, and STAT3 phosphorylation in the treated lung explants was analyzed. LIF supplementation significantly inhibited lung growth in spite of an increase in p44/42 phosphorylation. On the other hand, LIF inhibition significantly stimulated lung growth via p38 and Akt pathways. Conclusions/Significance The present study describes that LIF and its subunit receptor LIFRα are constitutively expressed during fetal lung development and that they have an inhibitory physiological role on fetal lung branching. PMID:22291973

  10. Basophil-derived IL-4 plays versatile roles in immunity.

    PubMed

    Yamanishi, Yoshinori; Karasuyama, Hajime

    2016-09-01

    Recent studies demonstrated that basophils play crucial and non-redundant roles in the immune system, in spite of the fact that they are the rarest granulocytes and represent less than 1 % of peripheral blood leukocytes. In response to various stimuli, basophils release effector molecules stored in their cytoplasmic granules, including chemical mediators and proteases, and also secrete cytokines and chemokines. In this review, we will focus on the physiological and pathological roles of basophil-derived IL-4. Basophils can readily produce large quantities of IL-4 and are therefore the important source of IL-4. Basophil-derived IL-4 has been shown to regulate other immune cells, including T cells, B cells, group 2 innate lymphoid cells, monocytes, and macrophages. It also acts on non-hematopoietic cells such as fibroblasts and endothelial cells. Those cells stimulated with basophil-derived IL-4 contribute to the positive or negative regulation of a variety of immune responses in health and disease, including protection against parasitic and bacterial infections, allergy, and autoimmune diseases. Thus, basophil-derived IL-4 plays versatile roles in immunity.

  11. “Auto-anti-IgE”: Naturally occurring IgG anti-IgE antibodies may inhibit allergen-induced basophil activation

    PubMed Central

    Chan, Yih-Chih; Ramadani, Faruk; Santos, Alexandra F.; Pillai, Prathap; Ohm-Laursen, Line; Harper, Clare E.; Fang, Cailong; Dodev, Tihomir S.; Wu, Shih-Ying; Ying, Sun; Corrigan, Christopher J.; Gould, Hannah J.

    2014-01-01

    Background Naturally occurring IgE-specific IgG autoantibodies have been identified in patients with asthma and other diseases, but their spectrum of functions is poorly understood. Objective Address the hypothesis that: (i) IgG anti-IgE autoantibodies are detectable in the serum of all subjects but elevated in asthmatic patients regardless of atopic status as compared with controls; (ii) some activate IgE-sensitized basophils; and (iii) some inhibit allergen-induced basophil activation. Methods IgE-specific IgG autoantibodies were detected and quantified in sera using ELISA. Sera were examined for their ability to activate IgE-sensitized human blood basophils in the presence and absence of allergen using a basophil activation test, and to inhibit allergen binding to specific IgE on a rat basophilic cell line stably expressing human FcεRI. Results IgG autoantibodies binding to both free and FcεRI-bound IgE were detected in patients with atopic and non-atopic asthma, as well as controls. While some were able to activate IgE-sensitised basophils, others inhibited allergen-induced basophil activation, at least partly by inhibiting binding of IgE to specific allergen. Conclusion Naturally occurring IgG anti-IgE autoantibodies may inhibit, as well as induce, basophil activation. They act in a manner distinct from therapeutic IgG anti-IgE antibodies such as omalizumab. They may at least partly explain why atopic subjects who make allergen-specific IgE never develop clinical symptoms, and why omalizumab therapy is of variable clinical benefit in severe atopic asthma. PMID:25112697

  12. The deleterious role of basophils in systemic lupus erythematosus

    PubMed Central

    Pellefigues, Christophe; Charles, Nicolas

    2013-01-01

    Systemic lupus erythematosus is a complex autoimmune disease of multifactorial origins. All compartments of the immune system appear to be affected, at least in some way, and to contribute to disease pathogenesis. Due to an escape from negative selection autoreactive T and B cells accumulate in SLE patients leading to the production of autoantibodies mainly raised against nuclear components and their subsequent deposition into target organs. We recently showed that basophils, in an IgE and IL-4 dependent manner, contribute to SLE pathogenesis by amplifying autoantibody production. Here, we summarize what we have learned about the deleterious role of basophils in lupus both in a mouse model and in SLE patients. We discuss which possible pathways could be involved in basophil activation and recruitment to secondary lymphoid organs during SLE, and how basophils may amplify autoantibody production. PMID:24209595

  13. Vorinostat, Cytarabine, and Etoposide in Treating Patients With Relapsed and/or Refractory Acute Leukemia or Myelodysplastic Syndromes or Myeloproliferative Disorders

    ClinicalTrials.gov

    2013-05-01

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  14. Human T-cell leukemia virus type 1 Tax protein transforms rat fibroblasts via two distinct pathways.

    PubMed Central

    Matsumoto, K; Shibata, H; Fujisawa, J I; Inoue, H; Hakura, A; Tsukahara, T; Fujii, M

    1997-01-01

    The human T-cell leukemia virus type 1 (HTLV-1) Tax protein activates the transcription of several cellular genes. This function is thought to play a critical role in the Tax-dependent transformation step in HTLV-1 leukemogenesis. Tax activates transcription via three enhancers: the cyclic AMP response element (CRE)-like sequence, the kappaB element, and the CArG box. Their involvement in the transformation of rat fibroblasts by Tax was examined by colony formation of Rat-1 cells in soft agar and Ras cooperative focus formation of rat embryo fibroblasts (REF). Among Tax mutants, those retaining activity for the CArG box transformed REF like wild-type Tax, while those inactive for the CArG box did not. Thus, the activation of the CArG box pathway is essential for the transformation of REF by Tax. In contrast, activation of the kappaB element correlated with the transformation of Rat-1 by Tax. These results show that Tax transforms rat fibroblasts via two distinct pathways. PMID:9151835

  15. Are Basophils and Mast Cells Masters in HIV Infection?

    PubMed

    Marone, Gianni; Varricchi, Gilda; Loffredo, Stefania; Galdiero, Maria Rosaria; Rivellese, Felice; de Paulis, Amato

    2016-01-01

    The World Health Organization AIDS epidemic update estimates that more than 37 million people are living with HIV infection. Despite the unprecedented success of antiretroviral treatments, significant challenges remain in the fight against HIV. In particular, how uninfected cells capture HIV and transmit virions to target cells remains an unanswered question. Tissue mast cells and peripheral blood basophils can be exposed to virions or HIV products during infection. Several HIV proteins (i.e., envelope glycoproteins gp120 and gp41, Tat, and Nef) can interact with distinct surface receptors expressed by human basophils and mast cells and modulate their functional responses at different levels. Additionally, several groups have provided evidence that human mast cells can be infected in vitro, as well as in vivo, by certain strains of HIV. Recently, it has been demonstrated that basophils purified from healthy donors and intestinal mast cells can efficiently capture HIV on their cell surface and, cocultured with CD4+ T cells, they can transfer the virus to the cocultured cells leading to infection. Direct contact between human basophils or intestinal mast cells and CD4+ T cells can mediate viral trans-infection of T cells through the formation of viral synapses. Thus, basophils and mast cells can provide a cellular basis for capturing and then spreading viruses throughout the body. Collectively, these findings suggest that human basophils and mast cells play a complex and possibly distinct role in HIV infection, warranting further investigations.

  16. [Human basophil degranulation test. Results of a modified technic (I)].

    PubMed

    Román Pérez, F; Berlanga Cortés, J A; Urquiă, M; Guerra Pasadas, F; Peña Martínez, J

    1986-01-01

    The degranulation of human basophils towards antigenic substances, to which they must be previously sensitized as a result of the antigen-antibody union at the membrane level, is a phenomenon that has an important application complementing diagnosis of diseases mediated by the Gell and Coombs classification of Type I Hypersensitivity, on which the principle of Human Basophils Degranulation Test (HBDT) was based. An essential requirement is to be able to collect an adequate quantity of basophils, as well as the visualization by means of a technique of convenient stain. In this work, we show a modified HBDT technique for basophil granulocytes staining. A total of 33 HBDT was carried out on patients sensitive to grass pollen and/or Olea europea pollen and/or D. pteronyssinus, and as controls, HBDT was done on healthy individuals with negative clinical history. Basophil enrichemnt from the circulating blood sample was done by means of centrifugation in Percoll density gradients of 1072, 1076, 1080 and 1082, and we obtained a higher number of basophils with a density of 1080 at 400 Xg for 30 minutes. The cellular bottom was resuspended in 600 microliters of PBS. We employed lyophilized antigenic extracts from grass pollen, Olea europea and D. pteronyssinus, employing weight/volume concentration of 10(-4), 10(-5), 10(-6) and 10(-7). The optimum dilutions were 10(-5) for grass pollen and D. pteronyssinus.

  17. Errors in basophil enumeration with 3 veterinary hematology systems and observations on occurrence of basophils in dogs.

    PubMed

    Lilliehöök, Inger; Tvedten, Harold W

    2011-12-01

    Most automated hematology analyzers cannot detect canine or feline basophils. However, many veterinary laboratories continue to report basophils as part of the automated 5-part differential leukocyte count for dogs and cats. The study objectives were to evaluate the performance of the Sysmex XT-2000iV, Advia 2120, and CELL-DYN 3500 hematology analyzers in detecting basophils using blood from dogs, cats, and rabbits with basophilia and to investigate the concurrence of basophilia and other hematologic changes, sex, and breed in dogs. One or more of the 3 hematology analyzers was used to analyze 11 canine blood samples with prominent basophilia (≥ 5%) based on a manual differential count. In addition, samples from 2 cats and 4 rabbits with basophilia were analyzed with the Advia 2120. Leukocyte cytograms were inspected for the likely location of basophil cell clusters. In a retrospective study of canine patients, reports of hematologic results that included a manual leukocyte differential count were identified using the laboratory information system and examined for the occurrence of basophilia and other hematologic changes, sex, and breed of the dogs. Canine basophils were not detected by the Sysmex XT-2000iV or CELL-DYN 3500 analyzers, and neither canine nor feline basophils were detected by the Advia 2120. The Advia was able to detect basophils in rabbits. On the Sysmex cytogram canine basophils were found slightly above or together with neutrophils. On the Advia Perox cytogram canine basophils were located in upper part of the lymphocyte box and in the area of large unstained cells (LUC). Dogs with marked basophilia often had concurrent eosinophilia, and basophilia may be found more frequently in Rottweiler dogs than in other breeds. In 5 dogs with marked basophilia and without eosinophilia, marked thrombocytosis and anemia were noted. Canine basophils were not detected by these automated hematology analyzers, and careful analysis of instrument graphical

  18. Leukemia - B-Cell Prolymphocytic Leukemia and Hairy Cell Leukemia

    MedlinePlus

    ... and Hairy Cell Leukemia: Introduction Request Permissions Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia: Introduction ... t k e P Types of Cancer Leukemia - B-cell Prolymphocytic Leukemia and Hairy Cell Leukemia Guide ...

  19. Chlorpheniramine-induced anaphylaxis diagnosed by basophil activation test.

    PubMed

    Lee, Hyun-Seung; Song, Woo-Jung; Lee, Ji-Won; Cho, Young-Yoon; Park, Han-Ki; Kang, Min-Gyu; Cho, Sang-Heon; Sohn, Seong-Wook

    2015-07-01

    Chlorpheniramine is a widely prescribed H1-antihistamine for relieving urticaria or histamine-mediated allergic reactions. However, although rare, it may cause immediate hypersensitivity reactions. The diagnosis is usually made by provocation test, but its application is often limited due to comorbidities or potential risk of severe reactions. In those cases, skin tests and basophil activation tests can be considered as additional diagnostic tests for the drug allergy. Here, we report a 33-year-old female with underlying chronic urticaria, who recurrently developed anaphylaxis after chlorpheniramine administration. Intradermal test showed positive responses in the patient at 0.02 mg/mL of chlorpheniramine, but not in healthy controls. Basophil activation test showed significant up-regulation of CD63 and CD203c by chlorpheniramine. The present case reminds the rare but potential allergic risk of chlorpheniramine, and also suggests the potential utility of basophil activation test in making the diagnosis.

  20. Basophil degranulation induced by oral poison ivy antigen.

    PubMed

    Shelley, W B; Resnik, S S

    1965-08-01

    Seven subjects shown by patch test to be sensitive to poison ivy oleoresin were challenged with graded oral doses of ivy extract. In each instance the circulating basophil leukocytes showed significant degranulation within one hour of challenge. This finding was interpreted as evidence of the presence of immediate-type circulating antibody to ivy antigen in these subjects. No drop in the absolute basophil count was noted, but with higher oral doses the degranulation persisted for several days. Thirteen control subjects showed no change in the basophil morphology or count, indicating that the resin at these levels was not toxic to this cell. All but one of the sensitive subjects showed objective patch test evidence of hyposensitization following the intensive three-week course of oral poison ivy antigen.

  1. Activation of the prolactin receptor gene by promoter insertion in a Moloney murine leukemia virus-induced rat thymoma.

    PubMed Central

    Barker, C S; Bear, S E; Keler, T; Copeland, N G; Gilbert, D J; Jenkins, N A; Yeung, R S; Tsichlis, P N

    1992-01-01

    The prolactin receptor (Prlr) and growth hormone receptor (Ghr) genes and the Moloney murine leukemia virus integration-2 (Mlvi-2) locus were mapped to mouse chromosome 15 and human chromosome 5 bands p12-p14. To examine the potential relationship between Mlvi-2 and the genes encoding the growth hormone receptor and the prolactin receptor, we determined the chromosomal location of all three loci in the rat, using a panel of rat-mouse somatic cell hybrids, and in the mouse, using a panel of (C57BL/6J x Mus spretus)F1 x C57BL/6J interspecific backcross mice. These analyses revealed that Ghr, Prlr, and Mlvi-2 map to chromosome 2 in the rat and to chromosome 15 in the mouse, in close proximity with each other. Pulsed-field gel electrophoresis of rat genomic DNA showed no overlaps between the gene encoding the prolactin receptor and the remaining loci. Moreover, expression of the prolactin receptor was not affected by provirus insertion in Mlvi-2. During these studies, however, we detected one T-cell lymphoma line (2779) in which the prolactin receptor gene was activated by provirus integration. Sequence analysis of polymerase chain reaction-derived cDNA clones showed that the prolactin receptor RNA message initiates at the 5' long terminal repeat and utilizes the splice donor site 5' of the gag gene to splice the viral sequences onto exon 1 of the prolactin receptor. This message is predicted to encode the intact prolactin receptor protein product. Exposure of the T-cell lymphoma line 2779 to prolactin promoted cellular proliferation. Images PMID:1404614

  2. High incidence of HAM/TSP-like symptoms in WKA rats after administration of human T-cell leukemia virus type 1-producing cells.

    PubMed Central

    Kushida, S; Mizusawa, H; Matsumura, M; Tanaka, H; Ami, Y; Hori, M; Yagami, K; Kameyama, T; Tanaka, Y; Yoshida, A

    1994-01-01

    We demonstrate a significantly high incidence of human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy (HAM)-or tropical spastic paraparesis (TSP)-like symptoms in WKA rats after injection with HTLV-1-producing MT-2 cells, while no symptoms were observed in F344 rats injected with MT-2 cells or in control WKA rats. Five of the eight (63%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 105 weeks of age, but none of seven MT-2-injected F344 rats or eight control WKA rats showed symptoms. This high incidence of HAM/TSP-like symptoms in WKA rats was statistically significant (P < 0.05). Six of the eight (75%) WKA rats injected with MT-2 cells showed HAM/TSP-like paraparesis at 108 weeks of age. HAM/TSP-like symptoms were also observed in one of the two WKA rats injected with HTLV-1-producing Ra-1 cells at 128 weeks of age. HTLV-1 provirus was detected in peripheral blood mononuclear cells in both WKA and F344 rats. The provirus was detected in the spinal cords of the HAM/TSP-like WKA rats that had severe neuropathological changes. WKA and F344 rats showed no significant difference in antibody response against HTLV-1 Gag antigen. However, the antibody response against the C-terminal half of gp46 HTLV-1 envelope protein was lower in WKA rats than in F344 rats. Pathological analysis of the HAM/TSP-like rats showed degeneration of the white matter of the spinal cord and peripheral nerves. These findings suggest that both the genetic background of the host and HTLV-1 infection are important in neuropathogenesis of HAM/TSP-like paraparesis in rats. Images PMID:7933104

  3. Reduction of human T-cell leukemia virus type 1 (HTLV-1) proviral loads in rats orally infected with HTLV-1 by reimmunization with HTLV-1-infected cells.

    PubMed

    Komori, Kazuya; Hasegawa, Atsuhiko; Kurihara, Kiyoshi; Honda, Takayuki; Yokozeki, Hiroo; Masuda, Takao; Kannagi, Mari

    2006-08-01

    Human T-cell leukemia virus type 1 (HTLV-1) persistently infects humans, and the proviral loads that persist in vivo vary widely among individuals. Elevation in the proviral load is associated with serious HTLV-1-mediated diseases, such as adult T-cell leukemia and HTLV-1-associated myelopathy/tropical spastic paraparesis. However, it remains controversial whether HTLV-1-specific T-cell immunity can control HTLV-1 in vivo. We previously reported that orally HTLV-1-infected rats showed insufficient HTLV-1-specific T-cell immunity that coincided with elevated levels of the HTLV-1 proviral load. In the present study, we found that individual HTLV-1 proviral loads established in low-responding hosts could be reduced by the restoration of HTLV-1-specific T-cell responses. Despite the T-cell unresponsiveness for HTLV-1 in orally infected rats, an allogeneic mixed lymphocyte reaction in the splenocytes and a contact hypersensitivity response in the skin of these rats were comparable with those of naive rats. HTLV-1-specific T-cell response in orally HTLV-1-infected rats could be restored by subcutaneous reimmunization with mitomycin C (MMC)-treated syngeneic HTLV-1-transformed cells. The reimmunized rats exhibited lower proviral loads than untreated orally infected rats. We also confirmed that the proviral loads in orally infected rats decreased after reimmunization in the same hosts. Similar T-cell immune conversion could be reproduced in orally HTLV-1-infected rats by subcutaneous inoculation with MMC-treated primary T cells from syngeneic orally HTLV-1-infected rats. The present results indicate that, although HTLV-1-specific T-cell unresponsiveness is an underlying risk factor for the propagation of HTLV-1-infected cells in vivo, the risk may potentially be reduced by reimmunization, for which autologous HTLV-1-infected cells are a candidate immunogen.

  4. The cromolyn binding protein constitutes the Ca2+ channel of basophils opening upon immunological stimulus.

    PubMed Central

    Mazurek, N; Schindler, H; Schürholz, T; Pecht, I

    1984-01-01

    Ca2+ channel opening has been proposed to be induced in the plasma membrane of mast cells and basophils upon crosslinking their Fc epsilon receptors. Here we report direct conductance measurements on planar lipid bilayers containing membrane components of rat basophils (RBL-2H3 line). These studies identify the Ca2+ channel-forming membrane component as the cromolyn binding protein [CBP, in which cromolyn is the anti-asthmatic drug 1,3-bis(2-carboxy-chromon-5-yloxy)-2-hydroxypropane]. Planar membranes were first formed from lipid vesicles containing unfractionated plasma membrane components prepared from RBL-2H3 cells. Conductance of these bilayers was induced by crosslinking IgE bound to the Fc epsilon receptors of this membrane by a specific polyvalent antigen. Channel conductance in the presence of only Ca2+ ions (2 mM) was 2 pS. When only sodium ions were present (150 mM), conductance was 10 pS. Upon addition of Ca2+ (2 mM) to the Na+ ion-containing solution, the conductance decreased from 10 pS to that of the Ca2+ ions--namely, 2pS. Open channel times were in the range of several hundred milliseconds. Conductance amplitudes and time characteristics were independent of the applied voltage. As our earlier studies revealed the essential role of the CBP in Ca2+ conductance of basophil membranes, we formed planar bilayers containing this isolated protein alone. Crosslinking of the CBP by a monoclonal antibody specific to it resulted in the appearance of channel conductances. All characteristics of these channels exhibited great similarity to those observed in planar membranes containing unfractionated RBL-2H3 membrane components. Moreover, in the latter membranes, the monoclonal anti-CBP antibody induced channel conductances that display an even closer similarity to those observed in membranes containing CBP alone. Conductances of both types of planar membranes, irrespective of the mode of activation used, were inhibited by cromolyn. Furthermore, the conductance

  5. Luteolin, a flavonoid, inhibits AP-1 activation by basophils

    SciTech Connect

    Hirano, Toru; Higa, Shinji; Arimitsu, Junsuke; Naka, Tetsuji; Ogata, Atsushi; Shima, Yoshihito; Fujimoto, Minoru; Yamadori, Tomoki; Ohkawara, Tomoharu; Kuwabara, Yusuke; Kawai, Mari; Matsuda, Hisashi; Yoshikawa, Masayuki; Maezaki, Naoyoshi; Tanaka, Tetsuaki; Kawase, Ichiro; Tanaka, Toshio . E-mail: ttanak@imed3.med.osaka-u.ac.jp

    2006-02-03

    Flavonoids including luteolin, apigenin, and fisetin are inhibitors of IL-4 synthesis and CD40 ligand expression by basophils. This study was done to search for compounds with greater inhibitory activity of IL-4 expression and to clarify the molecular mechanisms through which flavonoids inhibit their expression. Of the 37 flavonoids and related compounds examined, ayanin, luteolin, and apigenin were the strongest inhibitors of IL-4 production by purified basophils in response to anti-IgE antibody plus IL-3. Luteolin did not suppress Syk or Lyn phosphorylation in basophils, nor did suppress p54/46 SAPK/JNK, p38 MAPK, and p44/42 MAPK activation by a basophilic cell line, KU812 cells, stimulated with A23187 and PMA. However, luteolin did inhibit phosphorylation of c-Jun and DNA binding activity of AP-1 in nuclear lysates from stimulated KU812 cells. These results provide a fundamental structure of flavonoids for IL-4 inhibition and demonstrate a novel action of flavonoids that suppresses the activation of AP-1.

  6. Four Moloney murine leukemia virus-infected rat cell clones producing replication-defective particles: protein and nucleic acid analyses.

    PubMed Central

    Yoshimura, F K; Yamamura, J M

    1981-01-01

    Four cloned rat cell lines (NX-1 to -4) infected with Moloney murine leukemia virus and defective in virus replication were found to be all different by viral protein and nucleic acid analyses. All four clones produced noninfectious particles and, except for NX-2, at about the same level as wild type. Compared with wild-type virions these defective particles contained larger amounts of gag precursor proteins and very little or no p30 or p15. Analysis of intracellular precursor proteins revealed that NX-2 to -4 synthesized normal Pr65gag, whereas NX-1 produced a slightly smaller precursor. Both NX-1 and NX-4 synthesized an intracellular polyprotein with a size similar to that of wild-type Pr180 gag-pol. Restriction endonuclease analysis of NX-1 to -4 cellular DNA showed that each clone contained a single integrated provirus which possessed large terminal repeat sequences at both the 5' and 3' ends. The proviruses of NX-1 to -3 appeared normal by restriction endonuclease analysis, but NX-4 provirus had a deletion of 1,700 base pairs comprising part of the polymerase region. The noninfectious particles produced by all four clones packaged Moloney viral RNAs and rat RNAs of two different sizes. Images PMID:6165841

  7. BI 1002494, a Novel Potent and Selective Oral Spleen Tyrosine Kinase Inhibitor, Displays Differential Potency in Human Basophils and B Cells.

    PubMed

    Lamb, David J; Wollin, Stefan Lutz; Schnapp, Andreas; Bischoff, Daniel; Erb, Klaus J; Bouyssou, Thierry; Guilliard, Bernd; Strasser, Christine; Wex, Eva; Blum, Sylvia; Thaler, Eva; Nickel, Helga; Radmacher, Oliver; Haas, Hannah; Swantek, Jennifer L; Souza, Don; Canfield, Melissa; White, Della; Panzenbeck, Mark; Kashem, Mohammed A; Sanville-Ross, Mary; Kono, Takeshi; Sewald, Katherina; Braun, Armin; Obernolte, Helena; Danov, Olga; Schaenzle, Gerhard; Rast, Georg; Maier, Gerd-Michael; Hoffmann, Matthias

    2016-06-01

    BI 1002494 [(R)-4-{(R)-1-[7-(3,4,5-trimethoxy-phenyl)-[1,6]napthyridin-5-yloxy]-ethyl}pyrrolidin-2-one] is a novel, potent, and selective spleen tyrosine kinase (SYK) inhibitor with sustained plasma exposure after oral administration in rats, which qualifies this molecule as a good in vitro and in vivo tool compound. BI 1002494 exhibits higher potency in inhibiting high-affinity IgE receptor-mediated mast cell and basophil degranulation (IC50 = 115 nM) compared with B-cell receptor-mediated activation of B cells (IC50 = 810 nM). This may be explained by lower kinase potency when the physiologic ligand B-cell linker was used, suggesting that SYK inhibitors may exhibit differential potency depending on the cell type and the respective signal transduction ligand. A 3-fold decrease in potency was observed in rat basophils (IC50 = 323 nM) compared with human basophils, but a similar species potency shift was not observed in B cells. The lower potency in rat basophils was confirmed in both ex vivo inhibition of bronchoconstriction in precision-cut rat lung slices and in reversal of anaphylaxis-driven airway resistance in rats. The different cellular potencies translated into different in vivo efficacy; full efficacy in a rat ovalbumin model (that contains an element of mast cell dependence) was achieved with a trough plasma concentration of 340 nM, whereas full efficacy in a rat collagen-induced arthritis model (that contains an element of B-cell dependence) was achieved with a trough plasma concentration of 1400 nM. Taken together, these data provide a platform from which different estimates of human efficacious exposures can be made according to the relevant cell type for the indication intended to be treated.

  8. Leukemia - resources

    MedlinePlus

    The following organizations provide information on the different types of leukemia : Cancer Care -- www.cancercare.org/diagnosis/leukemia National Cancer Institute -- www.cancer.gov/types/leukemia The ...

  9. Basophil-derived IL-6 regulates TH17 cell differentiation and CD4 T cell immunity

    PubMed Central

    Yuk, Chae Min; Park, Hyeung Ju; Kwon, Bo-In; Lah, Sang Joon; Chang, Jun; Kim, Ji-Young; Lee, Kyung-Mi; Park, Su-Hyung; Hong, Seokchan; Lee, Seung-Hyo

    2017-01-01

    Basophils are rare, circulating granulocytes proposed to be involved in T helper (TH) type 2 immunity, mainly through secretion of interleukin (IL)-4. In addition to IL-4, basophils produce IL-6 and tumor necrosis factor (TNF)-α in response to immunoglobulin E (IgE) crosslinking. Differentiation of TH17 cells requires IL-6 and transforming growth factor (TGF)-β, but whether basophils play a significant role in TH17 induction is unknown. Here we show a role for basophils in TH17 cell development by using in vitro T cell differentiation and in vivo TH17-mediated inflammation models. Bone marrow derived-basophils (BMBs) and splenic basophils produce significant amounts of IL-6 as well as IL-4 following stimulation with IgE crosslink or cholera toxin (CT). In addition, through IL-6 secretion, BMBs cooperate with dendritic cells to promote TH17 cell differentiation. In the TH17 lung inflammation model, basophils are recruited to the inflamed lungs following CT challenge, and TH17 responses are significantly reduced in the absence of basophils or IL-6. Furthermore, reconstitution with wild-type, but not IL-6-deficient, basophils restored CT-mediated lung inflammation. Lastly, basophil-deficient mice showed reduced phenotypes of TH17-dependent experimental autoimmune encephalomyelitis. Therefore, our results indicate that basophils are an important inducer of TH17 cell differentiation, which is dependent on IL-6 secretion. PMID:28134325

  10. Leptin enhances survival and induces migration, degranulation, and cytokine synthesis of human basophils.

    PubMed

    Suzukawa, Maho; Nagase, Hiroyuki; Ogahara, Ikuko; Han, Kaiyu; Tashimo, Hiroyuki; Shibui, Akiko; Koketsu, Rikiya; Nakae, Susumu; Yamaguchi, Masao; Ohta, Ken

    2011-05-01

    Basophils are the rarest leukocytes in human blood, but they are now recognized as one of the most important immunomodulatory as well as effector cells in allergic inflammation. Leptin, a member of the IL-6 cytokine family, has metabolic effects as an adipokine, and it is also known to participate in the pathogenesis of inflammatory reactions. Because there is an epidemiologic relationship between obesity and allergy, we examined whether basophil functions are modified by leptin. We found that human basophils express leptin receptor (LepR) at both the mRNA and surface protein levels, which were upregulated by IL-33. Leptin exerted strong effects on multiple basophil functions. It induced a strong migratory response in human basophils, similar in potency to that of basophil-active chemokines. Also, leptin enhanced survival of human basophils, although its potency was less than that of IL-3. Additionally, CD63, a basophil activation marker expressed on the cell surface, was upregulated by leptin, an effect that was neutralized by blocking of LepR. Assessments of basophil degranulation and cytokine synthesis found that leptin showed a strong priming effect on human basophil degranulation in response to FcεRI aggregation and induced Th2, but not Th1, cytokine production by the cells. In summary, the present findings indicate that leptin may be a key molecule mediating the effects of adipocytes on inflammatory cells such as basophils by binding to LepR and activating the cellular functions, presumably exacerbating allergic inflammation.

  11. Clinical utility of a passive immune basophil activation test for the analysis of allergic transfusion reactions.

    PubMed

    Yasui, Kazuta; Matsuyama, Nobuki; Okamura-Shiki, Ikue; Ikeda, Takashi; Ishii, Kazuyoshi; Furuta, Rika A; Hirayama, Fumiya

    2017-09-01

    In previous studies, we demonstrated that the basophil activation test, which is performed using patient blood and the supernatants from transfused blood components, was able to elucidate not only the causative relationship between allergic transfusion reactions and the transfusion but also the mechanisms behind allergic transfusion reactions. However, for a large number of allergic transfusion reactions, patients are in a state of myelosuppression, and the basophil activation test cannot be performed for these patients because there are insufficient numbers of peripheral blood basophils. To overcome this obstacle, we developed a passive immune basophil activation test, in which patient plasma and residually transfused blood are used as the patient's sources of immunoglobulin E and allergen, respectively, whereas healthy volunteer basophils serve as the responder cell source. The passive immune basophil activation test was performed for two patients who had severe allergic transfusion reactions, using supernatants of the residual platelet concentrates and the patients' own immunoglobulin E. There were no differences in either surface immunoglobulin E or activation in response to allergens between untreated basophils and so-called quasi-basophils, in which immunoglobulin E was replaced by a third party's immunoglobulin E. In these patients, the supernatants of the residual platelet concentrates exclusively activated basophils in response to quasi-basophils onto which the patients' immunoglobulin E, but not a third party's immunoglobulin E, was bound. The passive immune basophil activation test may help clarify the causal relationship between allergic transfusion reactions and transfused blood, even when patients experience myelosuppression. © 2017 AABB.

  12. [Subacute myelogenous leukemia with Phildelphia chromosome].

    PubMed

    Brière, J; Castro-Malaspina, H; Tanzer, J; Bernard, J

    1975-01-01

    Twenty-five cases of a special pattern of chronic myeloid leukemia characterized, at the first evaluation, by excessive amount of blasts in blood or bone marrow (myeloblasts greater than or equal to 20%), Ph1 chromosome, and short evolution (median survival = 14,5 months) are reported. Age, spleen volume, white blood cell count are in keeping with those found in usual chronic myeloid leukemia (C.M.L.). However, clinical course is more severe with fever, bone pains, and anemia. Myelogibrosis, high circulating basophil polymorphonuclear count, platelet and megacaryocyte abnormalities (in morphology and number) are frequently associated with blastic excess. Subacute myeloid leukemia Ph1 positive (L.M.S. Ph1+) is proposed as an appellation for these cases in order to distinguish them from chronic myelocytic leukemia (C.M.L.) and other subacute myelogytic leukemias. The association of Ph1 chromosome excess of blasts and bone marrow fibrosis distinguishes L.M.S. Ph+ from: 1 degree C.M.L. with myelogibrosis; 2 degrees unusual cases of Ph1 positive myelofibrosis with myeloid metaplasia (M.M.M.); 3 degrees h1 positive acute leukemia. Forms of L.M.S. Ph+ with heavy blastic involvement are probably transitional cases with Ph1 acute myeloblastic leukemia. Prognosis is poorer than in C.M.L. but better than in acute blastic crisis occurring after chronic phase, which can be very similar to L.M.S. Ph1+, when seen for the first time.

  13. Anti-Bovine Programmed Death-1 Rat-Bovine Chimeric Antibody for Immunotherapy of Bovine Leukemia Virus Infection in Cattle.

    PubMed

    Okagawa, Tomohiro; Konnai, Satoru; Nishimori, Asami; Maekawa, Naoya; Ikebuchi, Ryoyo; Goto, Shinya; Nakajima, Chie; Kohara, Junko; Ogasawara, Satoshi; Kato, Yukinari; Suzuki, Yasuhiko; Murata, Shiro; Ohashi, Kazuhiko

    2017-01-01

    Blockade of immunoinhibitory molecules, such as programmed death-1 (PD-1)/PD-ligand 1 (PD-L1), is a promising strategy for reinvigorating exhausted T cells and preventing disease progression in a variety of chronic infections. Application of this therapeutic strategy to cattle requires bovinized chimeric antibody targeting immunoinhibitory molecules. In this study, anti-bovine PD-1 rat-bovine chimeric monoclonal antibody 5D2 (Boch5D2) was constructed with mammalian expression systems, and its biochemical function and antiviral effect were characterized in vitro and in vivo using cattle infected with bovine leukemia virus (BLV). Purified Boch5D2 was capable of detecting bovine PD-1 molecules expressed on cell membranes in flow cytometric analysis. In particular, Biacore analysis determined that the binding affinity of Boch5D2 to bovine PD-1 protein was similar to that of the original anti-bovine PD-1 rat monoclonal antibody 5D2. Boch5D2 was also capable of blocking PD-1/PD-L1 binding at the same level as 5D2. The immunomodulatory and therapeutic effects of Boch5D2 were evaluated by in vivo administration of the antibody to a BLV-infected calf. Inoculated Boch5D2 was sustained in the serum for a longer period. Boch5D2 inoculation resulted in activation of the proliferation of BLV-specific CD4(+) T cells and decrease in the proviral load of BLV in the peripheral blood. This study demonstrates that Boch5D2 retains an equivalent biochemical function to that of the original antibody 5D2 and is a candidate therapeutic agent for regulating antiviral immune response in vivo. Clinical efficacy of PD-1/PD-L1 blockade awaits further experimentation with a large number of animals.

  14. Nonlinear QSAR modeling for predicting cytotoxicity of ionic liquids in leukemia rat cell line: an aid to green chemicals designing.

    PubMed

    Gupta, Shikha; Basant, Nikita; Singh, Kunwar P

    2015-08-01

    Safety assessment and designing of safer ionic liquids (ILs) are among the priorities of the chemists and toxicologists today. Computational approaches have been considered as appropriate methods for prior safety assessment of chemicals and tools to aid in structural designing. The present study is an attempt to investigate the chemical attributes of a wide variety of ILs towards their cytotoxicity in leukemia rat cell line IPC-81 through the development of nonlinear quantitative structure-activity relationship (QSAR) models in the light of the OECD principles for QSAR development. Here, the cascade correlation network (CCN), probabilistic neural network (PNN), and generalized regression neural networks (GRNN) QSAR models were established for the discrimination of ILs in four categories of cytotoxicity and their end-point prediction using few simple descriptors. The diversity and nonlinearity of the considered dataset were evaluated through computing the Euclidean distance and Brock-Dechert-Scheinkman statistics. The constructed QSAR models were validated with external test data. The predictive power of these models was established through a variety of stringent parameters recommended in QSAR literature. The classification QSARs rendered the accuracy of >86%, and the regression models yielded correlation (R(2)) of >0.90 in test data. The developed QSAR models exhibited high statistical confidence and identified the structural elements of the ILs responsible for their cytotoxicity and, hence, could be useful tools in structural designing of safer and green ILs.

  15. Basophil-mediated protection against gastrointestinal helminths requires IgE-induced cytokine secretion

    PubMed Central

    Schwartz, Christian; Turqueti-Neves, Adriana; Hartmann, Susanne; Yu, Philipp; Nimmerjahn, Falk; Voehringer, David

    2014-01-01

    Basophils orchestrate protection against reinfections with gastrointestinal helminths and ticks, but the underlying mechanisms remain elusive. We investigated the role of Fc receptors on basophils, the antibody isotypes IgG1 and IgE, and basophil-derived IL-4/IL-13 during challenge infections with Heligmosomoides polygyrus and Nippostrongylus brasiliensis. Using mixed bone marrow chimeras, we found that activating Fc receptors on basophils were required for protective immunity but not for regulation of basophil homeostasis. Furthermore, rapid worm expulsion was impaired in IgE-deficient but not in IgG1-deficient mice. Basophils promoted the recruitment of other effector cells into the small intestine and induced expression of the antihelminthic proteins resistin-like molecule β and mucin 5ac. Selective deletion of IL-4/IL-13 in basophils resulted in impaired worm expulsion. Collectively, our results indicate that IgE-mediated activation of basophils and the release of basophil-derived IL-4/IL-13 are critical steps in protective immunity against helminths. Therefore, development of effective vaccines against helminths should consider boosting the IL-4/IgE/basophil axis of the immune system. PMID:25404305

  16. Evaluation of peripheral blood basophil activation by means of surface plasmon resonance imaging.

    PubMed

    Yanase, Yuhki; Hiragun, Takaaki; Yanase, Tetsuji; Kawaguchi, Tomoko; Ishii, Kaori; Hide, Michihiro

    2012-02-15

    Basophil activation in response to antigen may represent specificities of type I allergy of individuals and their reactions in the body. We previously demonstrated that surface plasmon resonance (SPR) sensor could detect the activation of human basophils in response to antigens. In this study, we further developed a technique based on SPR imaging (SPRI) system to detect reactions of individual basophils isolated from human blood, and investigated the potential of this sensor as a tool for diagnosis of type I allergy. To detect the change of refractive index (RI) in individual basophils, human basophils were isolated by negative selection with antibodies conjugated with magnetic beads, fixed on a gold film with anti-basophil antibody and stimulated with various antigens under the measurement of SPRI. The sensor could detect the reactions of individual basophils in response to specific antigens as well as non-specific activators. Moreover, the sensor well allocated two spots of basophils on a sensor chip and detected individual reactions to antigen. Thus, the technique developed in this study can visualize the effect of various stimuli or inhibitors on basophils as change of intracellular RI distribution at the single cell level. In combination with a device to rapidly isolate basophils from peripheral blood, this technique may be a useful tool as a high throughput screening system in clinical diagnosis for type I allergy.

  17. Basophile: Accurate Fragment Charge State Prediction Improves Peptide Identification Rates

    SciTech Connect

    Wang, Dong; Dasari, Surendra; Chambers, Matthew C.; Holman, Jerry D.; Chen, Kan; Liebler, Daniel; Orton, Daniel J.; Purvine, Samuel O.; Monroe, Matthew E.; Chung, Chang Y.; Rose, Kristie L.; Tabb, David L.

    2013-03-07

    In shotgun proteomics, database search algorithms rely on fragmentation models to predict fragment ions that should be observed for a given peptide sequence. The most widely used strategy (Naive model) is oversimplified, cleaving all peptide bonds with equal probability to produce fragments of all charges below that of the precursor ion. More accurate models, based on fragmentation simulation, are too computationally intensive for on-the-fly use in database search algorithms. We have created an ordinal-regression-based model called Basophile that takes fragment size and basic residue distribution into account when determining the charge retention during CID/higher-energy collision induced dissociation (HCD) of charged peptides. This model improves the accuracy of predictions by reducing the number of unnecessary fragments that are routinely predicted for highly-charged precursors. Basophile increased the identification rates by 26% (on average) over the Naive model, when analyzing triply-charged precursors from ion trap data. Basophile achieves simplicity and speed by solving the prediction problem with an ordinal regression equation, which can be incorporated into any database search software for shotgun proteomic identification.

  18. Basophile: Accurate Fragment Charge State Prediction Improves Peptide Identification Rates

    DOE PAGES

    Wang, Dong; Dasari, Surendra; Chambers, Matthew C.; ...

    2013-03-07

    In shotgun proteomics, database search algorithms rely on fragmentation models to predict fragment ions that should be observed for a given peptide sequence. The most widely used strategy (Naive model) is oversimplified, cleaving all peptide bonds with equal probability to produce fragments of all charges below that of the precursor ion. More accurate models, based on fragmentation simulation, are too computationally intensive for on-the-fly use in database search algorithms. We have created an ordinal-regression-based model called Basophile that takes fragment size and basic residue distribution into account when determining the charge retention during CID/higher-energy collision induced dissociation (HCD) of chargedmore » peptides. This model improves the accuracy of predictions by reducing the number of unnecessary fragments that are routinely predicted for highly-charged precursors. Basophile increased the identification rates by 26% (on average) over the Naive model, when analyzing triply-charged precursors from ion trap data. Basophile achieves simplicity and speed by solving the prediction problem with an ordinal regression equation, which can be incorporated into any database search software for shotgun proteomic identification.« less

  19. Basophile: Accurate Fragment Charge State Prediction Improves Peptide Identification Rates

    PubMed Central

    Wang, Dong; Dasari, Surendra; Chambers, Matthew C.; Holman, Jerry D.; Chen, Kan; Liebler, Daniel C.; Orton, Daniel J.; Purvine, Samuel O.; Monroe, Matthew E.; Chung, Chang Y.; Rose, Kristie L.; Tabb, David L.

    2013-01-01

    In shotgun proteomics, database search algorithms rely on fragmentation models to predict fragment ions that should be observed for a given peptide sequence. The most widely used strategy (Naive model) is oversimplified, cleaving all peptide bonds with equal probability to produce fragments of all charges below that of the precursor ion. More accurate models, based on fragmentation simulation, are too computationally intensive for on-the-fly use in database search algorithms. We have created an ordinal-regression-based model called Basophile that takes fragment size and basic residue distribution into account when determining the charge retention during CID/higher-energy collision induced dissociation (HCD) of charged peptides. This model improves the accuracy of predictions by reducing the number of unnecessary fragments that are routinely predicted for highly-charged precursors. Basophile increased the identification rates by 26% (on average) over the Naive model, when analyzing triply-charged precursors from ion trap data. Basophile achieves simplicity and speed by solving the prediction problem with an ordinal regression equation, which can be incorporated into any database search software for shotgun proteomic identification. PMID:23499924

  20. Leukemia inhibitory factor impairs structural and neurochemical development of rat visual cortex in vivo.

    PubMed

    Engelhardt, Maren; di Cristo, Graziella; Grabert, Jochen; Patz, Silke; Maffei, Lamberto; Berardi, Nicoletta; Wahle, Petra

    2017-03-01

    Minipump infusions into visual cortex in vivo at the onset of the critical period have revealed that the proinflammatory cytokine leukemia inhibitory factor (LIF) delays the maturation of thalamocortical projection neurons of the lateral geniculate nucleus, and tecto-thalamic projection neurons of the superior colliculus, and cortical layer IV spiny stellates and layer VI pyramidal neurons. Here, we report that P12-20 LIF infusion inhibits somatic maturation of pyramidal neurons and of all interneuron types in vivo. Likewise, DIV 12-20 LIF treatment in organotypic cultures prevents somatic growth GABA-ergic neurons. Further, while NPY expression is increased in the LIF-infused hemispheres, the expression of parvalbumin mRNA and protein, Kv3.1 mRNA, calbindin D-28k protein, and GAD-65 mRNA, but not of GAD-67 mRNA or calretinin protein is substantially reduced. Also, LIF treatment decreases parvalbumin, Kv3.1, Kv3.2 and GAD-65, but not GAD-67 mRNA expression in OTC. Developing cortical neurons are known to depend on neurotrophins. Indeed, LIF alters neurotrophin mRNA expression, and prevents the growth promoting action of neurotophin-4 in GABA-ergic neurons. The results imply that LIF, by altering neurotrophin expression and/or signaling, could counteract neurotrophin-dependent growth and neurochemical differentiation of cortical neurons.

  1. Lyn Kinase Controls Basophil GATA-3 Transcription Factor Expression and Induction of Th2 Cell Differentiation

    PubMed Central

    Charles, Nicolas; Watford, Wendy T.; Ramos, Haydeé L.; Hellman, Lars; Oettgen, Hans C.; Gomez, Gregorio; Ryan, John J.; O’Shea, John J.; Rivera, Juan

    2009-01-01

    Summary TH1/TH2 balance is key to host defense and its dysregulation has pathophysiological consequences. Basophils are important in TH2 differentiation. However, the factors controlling the onset and extent of basophil-mediated TH2 differentiation are unknown. Here, we demonstrate that Lyn kinase dampens basophil GATA-3 expression and the initiation and extent of TH2 differentiation. Lyn-null mice had a marked basophilia, a constitutive TH2 skewing that was exacerbated upon in vivo challenge of basophils, produced antibodies to a normally inert antigen, and failed to appropriately respond to a TH1 pathogen. The TH2 skewing was dependent on basophils, IgE and IL-4, but was independent of mast cells. Our findings demonstrate that basophil-expressed Lyn kinase exerts regulatory control on TH2 differentiation and function. PMID:19362019

  2. Flowcytometric analysis of basophil counts in human blood and inaccuracy of hematology analyzers.

    PubMed

    Ducrest, S; Meier, F; Tschopp, C; Pavlovic, R; Dahinden, C A

    2005-11-01

    Differential leukocyte counts are of proven clinical value, but information about basophil counts in normal and disease conditions is scarce although basophils are regarded as key effector cells in allergy. To establish and validate flowcytometric methods for counting basophils in peripheral human blood, to determine reference values, and to examine the accuracy of two widely used hematology analyzers. Basophils were measured in whole blood by flowcytometry after staining with antibodies against the IL-3-receptor (CD123) or the eotaxin-receptor (CCR3) combined with other markers used for gating or validation purposes. The basophil percentages in 95 healthy adults showed an excellent correlation between the two independent flowcytometric methods, demonstrating that both are accurate and precise. The most robust maker is CCR3, which seems to be sufficient to specifically identify basophils. Normal values of relative and absolute blood basophils counts were 0.22-1.28% and 0.014-0.087 G/L (95% reference intervals), respectively. Basophil counts measured with two hematology analyzers Coulter GEN-S and ADVIA-120 showed no correlation between these instruments. Comparing the data obtained by flowcytometry and the analyzers demonstrate that basophil counts of the GEN-S are erratic, while the ADVIA-120 gives at least an estimation of true basophil numbers. We provide a solid description and validation of a novel and rapid method for the flowcytometric enumeration of basophil in whole blood. The fact that the most heavily used Hematology autoanalyzer gives completely erroneous results could explain why basophils counts have not yet received recognition as a clinically useful diagnostic marker.

  3. The clinical utility of basophil activation testing in diagnosis and monitoring of allergic disease.

    PubMed

    Hoffmann, H J; Santos, A F; Mayorga, C; Nopp, A; Eberlein, B; Ferrer, M; Rouzaire, P; Ebo, D G; Sabato, V; Sanz, M L; Pecaric-Petkovic, T; Patil, S U; Hausmann, O V; Shreffler, W G; Korosec, P; Knol, E F

    2015-11-01

    The basophil activation test (BAT) has become a pervasive test for allergic response through the development of flow cytometry, discovery of activation markers such as CD63 and unique markers identifying basophil granulocytes. Basophil activation test measures basophil response to allergen cross-linking IgE on between 150 and 2000 basophil granulocytes in <0.1 ml fresh blood. Dichotomous activation is assessed as the fraction of reacting basophils. In addition to clinical history, skin prick test, and specific IgE determination, BAT can be a part of the diagnostic evaluation of patients with food-, insect venom-, and drug allergy and chronic urticaria. It may be helpful in determining the clinically relevant allergen. Basophil sensitivity may be used to monitor patients on allergen immunotherapy, anti-IgE treatment or in the natural resolution of allergy. Basophil activation test may use fewer resources and be more reproducible than challenge testing. As it is less stressful for the patient and avoids severe allergic reactions, BAT ought to precede challenge testing. An important next step is to standardize BAT and make it available in diagnostic laboratories. The nature of basophil activation as an ex vivo challenge makes it a multifaceted and promising tool for the allergist. In this EAACI task force position paper, we provide an overview of the practical and technical details as well as the clinical utility of BAT in diagnosis and management of allergic diseases.

  4. Enhancement of basophil chemotaxis in vitro by virus-induced interferon.

    PubMed Central

    Lett-Brown, M A; Aelvoet, M; Hooks, J J; Georgiades, J A; Thueson, D O; Grant, J A

    1981-01-01

    It is well established that viral infections may precipitate or worsen attacks of bronchial asthma. Furthermore, in symptomatic atopic subjects, the local accumulation of basophils and the production of a basophil chemotactic factor have been reported. We have investigated the effect of cell-free supernates from viral stimulated cultures of human mononuclear cells on the in vitro migration of human basophils. Our results show the presence of a factor in these culture supernates that enhances the migration of basophils toward two separate chemoattractants, a peptide from C5 and a lymphokine. The enhancing activity, while affecting basophil migration, did not change the response of monocytes. The enhancing activity resembled viral-induced interferon when (a) pH 2 stability, (b) heat resistance, (c) trypsin sensitivity, and (d) species-specificity were compared. Finally, the enhancing activity for basophil chemotaxis and the interferon titer were highly correlated in preparations with a 10(4)-fold difference in interferon specific activity. Our studies show that viral-induced interferon can augment the in vitro chemotactic response of basophils. Because mediators present in basophils may be involved in the pathogenesis of immediate hypersensitivity, the modulation of basophil movement by interferon suggests a possible mechanism for the association between viral infections and atopic disorders. PMID:6161946

  5. In vitro Biphasic Effect of Honey Bee Venom on Basophils from Screened Healthy Blood Donors

    PubMed Central

    Zanoni, Giovanna; Ortolani, Riccardo; Vella, Antonio

    2011-01-01

    Apis mellifera L. bee venom is the most studied hymenoptera allergen, but many aspects of its action on human basophils remain unclear. Allergologists seek evidence of the effectiveness of bee venom immunotherapy as this approach is the chosen treatment for systemic allergic reactions. The effect of bee venom on human basophils in vitro has not been studied in detail for many reasons, including the paucity of basophils in peripheral blood, inter-individual basophil response variability, and the reliability and predictability of basophil activation tests. We conducted a brief preliminary survey of the effect of Apis bee venom on healthy asymptomatic (non-allergic) subjects. A dose of an aqueous commercial extract of Apis bee venom as high as 10 µg/mL activated resting basophils (CD63=+80-90%, CD203c=+30%), while it inhibited the expression of CD63 (-50%) following basophil stimulation by the soluble agonists formyl-Met-Leu-Phe or anti-IgE. The activation of resting basophils appeared to be dose-related. Only when basophils were activated with an IgE-mediated agonist, did bee venom extract exhibit a possible priming mechanism at the lowest doses used only via CD63, while it was ineffective via CD203c. Autocrine interleukin-3 may play a role in the observed biphasic behavior. PMID:21217927

  6. Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line

    PubMed Central

    Han, Yueqin; Zhu, Yanping; Wang, Jinshen; Han, Yanqin; Qin, Daogang; Yang, Qiaozhi; Sun, Xiaojing; Chen, Lijun

    2016-01-01

    Objective(s): To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. Materials and Methods: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. Results: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. Conclusion: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia. PMID:27746864

  7. Repairing effects of interleukin 11 (IL-11) towards high dose methotrexate-induced rat small intestinal mucositis and its impacts on T-lymphoblastic leukemia cell line

    PubMed Central

    Han, Yueqin; Zhu, Yanping; Wang, Jinshen; Han, Yanqin; Qin, Daogang; Yang, Qiaozhi; Sun, Xiaojing; Chen, Lijun

    2016-01-01

    Objective(s): To investigate the efficacy of interleukin 11 (IL-11) towards the high dose methotrexate (HDMTX)-concurrent rat small intestinal mucositis and its impacts on the proliferation of the human T-lymphoblastic leukemia (CEM) cell line. Materials and Methods: 95 Wistar rats were randomly divided into five groups, the normal control group (A), the methotrexate (MTX) control group (B), the IL-11-pre-treated high-dose group (C), the post-IL-11-treatment high-dose group (D) and the post-IL-11-treatment low-dose group (E). After the intraperitoneal injection of MTX in the groups B-E, the rats were sacrificed at 1, 3, 5 and 7 days. The mortality, morphological and ultrastructural changes of small intestine of each group were observed. The cells were then cultured in vitro, and the MTT method was used to investigate the effects of different concentration of IL-11 on CEM proliferation and also on HDMTX-induced mucositis. Results: IL-11 could reduce the intestinal histopathological score, increase the height of small intestinal villi, promote the proliferation of intestinal lacunar cells and reduce the mortality rate of rats. The IL-11 pre-treatment group exhibited the best efficacies, demonstrating significant difference with the control group (P<0.01). In addition, the proliferation of CEM was not promoted, indicating that IL-11 could not inhibit HDMTX. Conclusion: IL-11 could reduce the severity of HDMTX-induced intestinal mucositis, and improve the survival rate of experimental rats, and could be safely used as the adjuvant treatment of HDMTX in childhood leukemia[PARANDCO1]. PMID:27635197

  8. Chronic myelogenous leukemia (CML)

    MedlinePlus

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... nuclear disaster. It takes many years to develop leukemia from radiation exposure. Most people treated for cancer ...

  9. Childhood Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  10. Basophil Activation Test with Food Additives in Chronic Urticaria Patients

    PubMed Central

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU. PMID:24527415

  11. Basophil activation test with food additives in chronic urticaria patients.

    PubMed

    Kang, Min-Gyu; Song, Woo-Jung; Park, Han-Ki; Lim, Kyung-Hwan; Kim, Su-Jung; Lee, Suh-Young; Kim, Sae-Hoon; Cho, Sang-Heon; Min, Kyung-Up; Chang, Yoon-Seok

    2014-01-01

    The role of food additives in chronic urticaria (CU) is still under investigation. In this study, we aimed to explore the association between food additives and CU by using the basophil activation test (BAT). The BAT using 15 common food additives was performed for 15 patients with CU who had a history of recurrent urticarial aggravation following intake of various foods without a definite food-specific IgE. Of the 15 patients studied, two (13.3%) showed positive BAT results for one of the tested food additives. One patient responded to monosodium glutamate, showing 18.7% of CD203c-positive basophils. Another patient showed a positive BAT result to sodium benzoate. Both patients had clinical correlations with the agents, which were partly determined by elimination diets. The present study suggested that at least a small proportion of patients with CU had symptoms associated with food additives. The results may suggest the potential utility of the BAT to identity the role of food additives in CU.

  12. Polymerization of actin does not regulate desensitization in human basophils

    PubMed Central

    MacGlashan, Donald; Vilariño, Natalia

    2009-01-01

    Previous studies have suggested that maintenance of IgE-mediated signaling results from regulation of the activity of signaling complexes by actin polymerization. This process is also hypothesized to be related to desensitization of basophils and mast cells. Recent studies demonstrated that any signaling process dependent on syk or PI-3K activity cannot be a mechanism of desensitization, and in this context, syk and PI-3K inhibitors were found to inhibit actin polymerization. Inhibitors of actin polymerization were tested for their effect on desensitization of human peripheral blood basophils. Latrunculin A, in particular, removed all resting and stimulated f-actin but did not inhibit desensitization. Cytochalasin D and latrunculin A also did not reverse the loss of syk phosphorylation that accompanies desensitization. These results demonstrate that desensitization mechanisms are not dependent on actin polymerization. In this context, it was also shown that progressive immobilization of FcεRI during aggregation was sensitive to syk or actin polymerization inhibition. Therefore, desensitization is also not dependent on receptor immobilization. These studies demonstrate that desensitization is not the result of two signaling pathways once considered relevant to down-regulation of IgE-mediated signaling. PMID:19150851

  13. Constituents from oak bark (Quercus robur L.) inhibit degranulation and allergic mediator release from basophils and mast cells in vitro.

    PubMed

    Lorenz, Peter; Heinrich, Miriam; Garcia-Käufer, Manuel; Grunewald, Franziska; Messerschmidt, Silke; Herrick, Anja; Gruber, Kim; Beckmann, Christiane; Knoedler, Matthias; Huber, Roman; Steinborn, Carmen; Stintzing, Florian C; Gründemann, Carsten

    2016-12-24

    Oak bark has been used since ancient times in Europaen ethnomedicine because of its adstringent, antimicrobial and hemostatic features, e.g. as a remedy for the treatment of wounds and skin diseases. Oak bark tannins are considered as bioactive natural products, interacting with surface proteins of mucous membranes and might be beneficial for the treatment of allergic diseases. This study investigated the effect of an oak bark decoction (OBD) and isolated tannin fractions on the degranulation capacity and cytokine/chemokine release from rat basophilic cells and human mast cells in vitro, which are essential for the initiation of early- and late-phase allergic reactions. By chromatographic separation on Sephadex(®) LH-20 high- and low-molecular weight tannins were separated from OBD and the tannin composition analyzed by HPLC(DAD)-MS(n). Then, the OBD and its fractions were tested in degranulation (β-hexosaminidase activity) of allergen-specific-activated basophilic cells in a photometric assay. The OBD and the high-molecular tannin fraction showed a dose-dependent inhibition of cell degranulation. Furthermore, the OBD and particularly its high molecular weight tannin fraction exhibited an inhibitory activity on the IL-8-, IL-6- and TNF-α-secretion from stimulated human mast cells, detected and quantified by ELISA. The OBD and its high-molecular weight tannins revealed an impact on allergic mediator release of basophilic cells and human mast cells and thereby provide a rationale for the topical treatment with OBD preparations. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  14. Cysteine protease antigens cleave CD123, the α subunit of murine IL-3 receptor, on basophils and suppress IL-3-mediated basophil expansion

    SciTech Connect

    Nishikado, Hideto; Fujimura, Tsutomu; Taka, Hikari; Mineki, Reiko; Ogawa, Hideoki; Okumura, Ko; Takai, Toshiro

    2015-05-01

    Th2 type immune responses are essential for protective immunity against parasites and play crucial roles in allergic disorders. Helminth parasites secrete a variety of proteases for their infectious cycles including for host entry, tissue migration, and suppression of host immune effector cell function. Furthermore, a number of pathogen-derived antigens, as well as allergens such as papain, belong to the family of cysteine proteases. Although the link between protease activity and Th2 type immunity is well documented, the mechanisms by which proteases regulate host immune responses are largely unknown. Here, we demonstrate that the cysteine proteases papain and bromelain selectively cleave the α subunit of the IL-3 receptor (IL-3Rα/CD123) on the surface of murine basophils. The decrease in CD123 expression on the cell surface, and the degradation of the extracellular domain of recombinant CD123 were dependent on the protease activity of papain and bromelain. Pre-treatment of murine basophils with papain resulted in inhibition of IL-3-IL-3R signaling and suppressed IL-3- but not thymic stromal lymphopoietin-induced expansion of basophils in vitro. Our unexpected findings illuminate a novel mechanism for the regulation of basophil functions by protease antigens. Because IL-3 plays pivotal roles in the activation and proliferation of basophils and in protective immunity against helminth parasites, pathogen-derived proteases might contribute to the pathogenesis of infections by regulating IL-3-mediated functions in basophils. - Highlights: • We identified the murine IL3R as a novel target of papain-family cysteine proteases. • Papain-family cysteine proteases cleaved IL3Rα/CD123 on murine basophils. • Papain suppressed IL3- but not TSLP-induced expansion of murine basophils. • The inactivation of IL3R might be a strategy for pathogens to suppress host immunity.

  15. Distinct Contributory Factors Determine Basophil-Allergen Sensitivity in Grass Pollen Rhinitis and in Anaphylactic Wasp Venom Allergy.

    PubMed

    Korošec, Peter; Šilar, Mira; Kopač, Peter; Eržen, Renato; Zidarn, Mihaela; Košnik, Mitja

    2016-01-01

    We sought to determine whether basophil-allergen sensitivity could be transferred to donor basophils by passive IgE sensitisation in allergic rhinitis and anaphylactic Hymenoptera venom hypersensitivity. We studied 15 wasp venom-, 19 grass pollen- and 2 house dust mite-allergic patients, 2 healthy donors, and 8 wasp venom-allergic donors. In all subjects, we first evaluated the initial basophil response to wasp venom, grass pollen, or house dust mite allergen. Donor basophils were then stripped, sensitised with the different patients' serum IgE, and challenged with the corresponding allergen. The CD63 response of donor basophils was then compared with initial basophil responses. In wasp venom-allergic subjects, the IgE transfer did not reflect the initial basophil-allergen sensitivity, because the venom IgE of subjects with high or low basophil sensitivity induced comparable responsiveness in healthy donor basophils. Furthermore, vice versa, when we sensitised the donor basophils of wasp venom-allergic individuals with different wasp venom or house dust mite IgE, we demonstrated that their response was predictable by their initial basophil allergen sensitivity. In the rhinitis allergy model, the IgE transfer correlated with the patients' initial basophil responsiveness because the grass pollen IgE of the subjects with high basophil allergen sensitivity induced significantly higher responsiveness of donor basophils than the IgE of subjects with initially low basophil allergen sensitivity. Our results suggest that basophil allergen sensitivity evaluated by flow-cytometric CD63 analysis depends on two distinct contribution factors. In anaphylactic Hymenoptera allergy, the major factor was intrinsic cellular sensitivity, whereas in pollen allergy, the major factor was allergen-specific IgE on the cell surface. © 2016 S. Karger AG, Basel.

  16. Leukemia inhibitory factor induces sympathetic sprouting in intact dorsal root ganglia in the adult rat in vivo

    PubMed Central

    Thompson, Stephen W N; Majithia, Anooj A

    1998-01-01

    The role of the cytokine leukemia inhibitory factor (LIF) in axotomy-induced sprouting of postganglionic sympathetic fibres into the dorsal root ganglia was examined in the adult rat.Immunocytochemistry was used to study the distribution and density of tyrosine hydroxylase-immunoreactive (TH-IR) fibres within the lumbar dorsal root ganglia and lumbar spinal nerves 14 days following continuous intrathecal infusion of LIF (0.33 mg ml−1), or 14 days following unilateral peripheral nerve axotomy.In LIF-treated animals, numerous pericellular TH-IR basket-like structures were observed surrounding sensory neurones, which were absent from controls.The number of TH-IR fibres within the L3, L4 and L5 spinal nerves was significantly higher in LIF-treated animals than in control or saline-treated animals (P < 0.01, Student's t test).Unilateral ligation of the L4 spinal nerve or unilateral sciatic nerve ligation was also associated with the formation of TH-IR baskets around sensory neurones and a significant increase in the number of TH-IR fibres within the lumbar spinal nerves (P < 0.01, Student's t test).The percentage of neurones surrounded by TH-IR baskets within the L3 and L4 dorsal root ganglia following sciatic axotomy was significantly reduced in animals treated continuously for 2 weeks with a monoclonal antibody against the LIF receptor motif, gp130 (0.833 mg ml−1) (P < 0.05, Mann-Whitney U test). Antibody treatment did not reduce the axotomy-induced increase in TH-IR fibres within lumbar spinal nerves.These results demonstrate that exogenous application of the axotomy-associated cytokine LIF is associated with sprouting of uninjured postganglionic sympathetic neurones around sensory neurones within the dorsal root ganglion. It is likely that increased LIF expression following peripheral axotomy plays an important role in the novel sympathetic sprouting observed within sensory ganglia following peripheral nerve injury. PMID:9503339

  17. Resveratrol Suppresses Cytokine Production Linked to FcεRI-MAPK Activation in IgE-Antigen Complex-Exposed Basophilic Mast Cells and Mice.

    PubMed

    Han, Seon-Young; Choi, Yean-Jung; Kang, Min-Kyung; Park, Jung Han Yoon; Kang, Young-Hee

    2015-01-01

    A complicated interplay between resident mast cells and other recruited inflammatory cells contributes to the development and progression of allergic inflammation entailing the promotion of T helper 2 (Th2) cytokine responses. The current study examined whether resveratrol suppressed the production of inflammatory Th2 cytokines in cultured rat basophilic leukemia RBL-2H3 cells. Cells pre-treated with resveratrol nontoxic at 1–25 μM were sensitized with anti-dinitrophenyl (anti-DNP), and subsequently stimulated by dinitrophenyl-human serum albumin (DNP–HSA) antigen. Resveratrol dose-dependently diminished the secretion of interleukin (IL)-3, IL-4, IL-13 as well as tumor necrosis factor (TNF)-α by the antigen stimulation from sensitized cells. It was found that resveratrol mitigated the phosphorylation of p38 MAPK, ERK, and JNK elevated in mast cells exposed to Fc epsilon receptor I (FcεRI)-mediated immunoglobulin E (IgE)-antigen complex. The FcεRI aggregation was highly enhanced on the surface of mast cells following the HSA stimulation, which was retarded by treatment with 1–25 μM resveratrol. The IgE-receptor engagement rapidly induced tyrosine phosphorylation of c-Src-related focal adhesion protein paxillin involved in the cytoskeleton rearrangement. The FcεRI-mediated rapid activation of c-Src and paxillin was attenuated in a dose-dependent manner. In addition, the paxillin activation entailed p38 MAPK and ERK-responsive signaling, but the JNK activation was less involved. Consistently, oral administration of resveratrol reduced the tissue level of phosphorylated paxillin in the dorsal skin of DNP–HSA-challenged mice. The other tyrosine kinase Tyk2-STAT1 signaling was activated in the dorsal epidermis of antigen-exposed mice, which was associated with allergic inflammation. These results showed that resveratrol inhibited Th2 cytokines- and paxillin-linked allergic responses dependent upon MAPK signaling. Therefore, resveratrol may possess the

  18. Intravenous immunoglobulin-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients

    PubMed Central

    Sharma, Meenu; Schoindre, Yoland; Hegde, Pushpa; Saha, Chaitrali; Maddur, Mohan S.; Stephen-Victor, Emmanuel; Gilardin, Laurent; Lecerf, Maxime; Bruneval, Patrick; Mouthon, Luc; Benveniste, Olivier; Kaveri, Srini V.; Bayry, Jagadeesh

    2014-01-01

    Intravenous immunoglobulin (IVIg) is used in the therapy of various autoimmune and inflammatory diseases. Recent studies in experimental models propose that anti-inflammatory effects of IVIg are mainly mediated by α2,6-sialylated Fc fragments. These reports further suggest that α2,6-sialylated Fc fragments interact with DC-SIGN+ cells to release IL-33 that subsequently expands IL-4-producing basophils. However, translational insights on these observations are lacking. Here we show that IVIg therapy in rheumatic patients leads to significant raise in plasma IL-33. However, IL-33 was not contributed by human DC-SIGN+ dendritic cells and splenocytes. As IL-33 has been shown to expand basophils, we analyzed the proportion of circulating basophils in these patients following IVIg therapy. In contrast to mice data, IVIg therapy led to basophil expansion only in two patients who also showed increased plasma levels of IL-33. Importantly, the fold-changes in IL-33 and basophils were not correlated and we could hardly detect IL-4 in the plasma following IVIg therapy. Thus, our results indicate that IVIg-induced IL-33 is insufficient to mediate basophil expansion in autoimmune patients. Hence, IL-33 and basophil-mediated anti-inflammatory mechanism proposed for IVIg might not be pertinent in humans. PMID:25012067

  19. Flux change in basophil membrane is not the main pathogenesis for hypersensitivity

    PubMed Central

    Wiwanitkit, Viroj

    2007-01-01

    The oxidation process is one of the most important natural processes. Oxidative change in hypersensitivity is believed to be an important process in the pathogenesis. However, the clear explanation on the transmembrane flux change of basophil and its correlation to hypersensitivity pathogenesis has never been reported. Here, the author determines the transmembrane oxidation flux in basophil. The simulation test to determine the oxidation flux change based on nanomedicine technique is used. Of interest, no change of flux can be detected. Therefore, this work can support the finding that the oxidation flux change is not an important part in the pathogenesis of basophil-related hypersensitivity. PMID:18203432

  20. The history of the controversial relationship between mast cells and basophils.

    PubMed

    Crivellato, Enrico; Nico, Beatrice; Ribatti, Domenico

    2011-12-30

    Work on mast cells and basophils began with their identification by Paul Ehrlich at the end of the 19th century. Mast cells and basophils were immediately perceived as closely linked cells and early nomenclature formulated by Ehrlich himself, i.e., tissue "Mastzellen" and blood "Mastzellen", reflected this unifying viewpoint. With time, important functional affinities but also substantial diversities were recognized. This review article focuses on the historical development of the concept of mast cell/basophil specificity, from the initial identification of these cells to current studies. Copyright © 2011 Elsevier B.V. All rights reserved.

  1. Modulation of Basophils' Degranulation and Allergy-Related Enzymes by Monomeric and Dimeric Naphthoquinones

    PubMed Central

    Pinho, Brígida R.; Sousa, Carla; Valentão, Patrícia; Oliveira, Jorge M. A.; Andrade, Paula B.

    2014-01-01

    Allergic disorders are characterized by an abnormal immune response towards non-infectious substances, being associated with life quality reduction and potential life-threatening reactions. The increasing prevalence of allergic disorders demands for new and effective anti-allergic treatments. Here we test the anti-allergic potential of monomeric (juglone, menadione, naphthazarin, plumbagin) and dimeric (diospyrin and diosquinone) naphthoquinones. Inhibition of RBL-2H3 rat basophils' degranulation by naphthoquinones was assessed using two complementary stimuli: IgE/antigen and calcium ionophore A23187. Additionally, we tested for the inhibition of leukotrienes production in IgE/antigen-stimulated cells, and studied hyaluronidase and lipoxidase inhibition by naphthoquinones in cell-free assays. Naphthazarin (0.1 µM) decreased degranulation induced by IgE/antigen but not A23187, suggesting a mechanism upstream of the calcium increase, unlike diospyrin (10 µM) that reduced degranulation in A23187-stimulated cells. Naphthoquinones were weak hyaluronidase inhibitors, but all inhibited soybean lipoxidase with the most lipophilic diospyrin, diosquinone and menadione being the most potent, thus suggesting a mechanism of competition with natural lipophilic substrates. Menadione was the only naphthoquinone reducing leukotriene C4 production, with a maximal effect at 5 µM. This work expands the current knowledge on the biological properties of naphthoquinones, highlighting naphthazarin, diospyrin and menadione as potential lead compounds for structural modification in the process of improving and developing novel anti-allergic drugs. PMID:24587235

  2. The Evolution of Human Basophil Biology from Neglect towards Understanding of Their Immune Functions

    PubMed Central

    Steiner, Markus; Huber, Sara; Harrer, Andrea

    2016-01-01

    Being discovered long ago basophils have been neglected for more than a century. During the past decade evidence emerged that basophils share features of innate and adaptive immunity. Nowadays, basophils are best known for their striking effector role in the allergic reaction. They hence have been used for establishing new diagnostic tests and therapeutic approaches and for characterizing natural and recombinant allergens as well as hypoallergens, which display lower or diminished IgE-binding activity. However, it was a long way from discovery in 1879 until identification of their function in hypersensitivity reactions, including adverse drug reactions. Starting with a historical background, this review highlights the modern view on basophil biology. PMID:28078302

  3. Avian erythroblastosis virus transforms a novel mast cell-basophil precursor target in the Japanese quail.

    PubMed Central

    Moscovici, M G; Siegel, M L; Moscovici, C

    1989-01-01

    Hematopoietic cells of the Japanese quail were transformed by avian erythroblastosis virus in vivo and in vitro. In both circumstances, the infected hematopoietic tissues exhibited a dual oncogenic response of erythroid and mast cell-basophil elements. The erythroid transformants escaped the avian erythroblastosis virus block in differentiation and progressed to hemoglobinization. Resulting basophilic cells were morphologically, biochemically, and ultrastructurally identical to mast cell-basophils observed in other species. None of the virally transformed cells actively produced reverse transcriptase activity. Nonproducer cell lines synthesized viral RNA and both v-erbA and v-erbB proteins. These results indicate that the Japanese quail has a viral target cell different from that of the chicken. The implications of a single bipotential transformation target yielding both erythroid and mast cell-basophil colonies is discussed. Images PMID:2539521

  4. The mechanism of basophil histamine release in patients with periodontal disease.

    PubMed Central

    Olsson-Wennström, A; Wennström, J L; Mergenhagen, S E; Siraganian, R P

    1978-01-01

    Histamine release from washed peripheral blood basophils of thirty-three subjects with varying degrees of periodontal disease was studied. Dental plaque, serum and basophil leucocytes were collected from individual patients. There was no histamine release when autologous, washed sonicated plaque was added to leucocytes. However, the incubation of autologous plaque with serum at 37 degrees C for 30 min generated a factor which induced histamine release from basophils. This serum factor was stable to heat (56 degrees C, 30 min), eluted from a Sephadex G-100 column at a volume corresponding to a molecular weight of approximately 16,000 daltons and its action was inhibited by antibody to C5. This factor, therefore, is probably C5a. There was a variation in the degree of histamine release seen with the leucocytes of different donors. This variability was a property of the basophil rather than a function of the serum. Basophils from patients with gingival indices of 0.5 to 1.0 had significantly more histamine release than basophils from patients with gingival indices of less than 0.5 or greater than 1.5 (P less than 0.001). These experiments demonstrate that dental plaque activates serum to form C5a which in turn releases histamine from basophils. However, these experiments do not indicate a role for IgE in this reaction since the direct interaction of plaque with basophils did not cause histamine release. The release of mediators from mast cells could play an important role in the induction of the inflammatory response in periodontal disease. PMID:81729

  5. Selective ablation of basophils in mice reveals their nonredundant role in acquired immunity against ticks

    PubMed Central

    Wada, Takeshi; Ishiwata, Kenji; Koseki, Haruhiko; Ishikura, Tomoyuki; Ugajin, Tsukasa; Ohnuma, Naotsugu; Obata, Kazushige; Ishikawa, Ryosuke; Yoshikawa, Soichiro; Mukai, Kaori; Kawano, Yohei; Minegishi, Yoshiyuki; Yokozeki, Hiroo; Watanabe, Naohiro; Karasuyama, Hajime

    2010-01-01

    Ticks are ectoparasitic arthropods that can transmit a variety of microorganisms to humans and animals during blood feeding, causing serious infectious disorders, including Lyme disease. Acaricides are pharmacologic agents that kill ticks. The emergence of acaricide-resistant ticks calls for alternative control strategies for ticks and tick-borne diseases. Many animals develop resistance to ticks after repeated infestations, but the nature of this acquired anti-tick immunity remains poorly understood. Here we investigated the cellular and molecular mechanisms underlying acquired resistance to Haemaphysalis longicornis ticks in mice and found that antibodies were required, as was IgFc receptor expression on basophils but not on mast cells. The infiltration of basophils at tick-feeding sites occurred during the second, but not the first, tick infestation. To assess the requirement for basophil infiltration to acquired tick resistance, mice expressing the human diphtheria toxin receptor under the control of the mast cell protease 8 (Mcpt8) promoter were generated. Diphtheria toxin administration to these mice selectively ablated basophils. Diphtheria toxin–mediated basophil depletion before the second tick infestation resulted in loss of acquired tick resistance. These data provide the first clear evidence, to our knowledge, that basophils play an essential and nonredundant role in antibody-mediated acquired immunity against ticks, which may suggest new strategies for controlling tick-borne diseases. PMID:20664169

  6. Mutual Interaction of Basophils and T Cells in Chronic Inflammatory Diseases

    PubMed Central

    Sarfati, Marika; Wakahara, Keiko; Chapuy, Laurence; Delespesse, Guy

    2015-01-01

    Basophils are, together with mast cells, typical innate effector cells of allergen-induced IgE-dependent allergic diseases. Both cell types express the high-affinity receptor for IgE (FcεR1), release histamine, inflammatory mediators, and cytokines following FcεR1 cross-linking. Basophils are rare granulocytes in blood, lymphoid, and non-lymphoid tissues, and the difficulties to detect and isolate these cells has hampered the study of their biology and the understanding of their possible role in pathology. Furthermore, the existence of other FcεR1-expressing cells, including professional Ag-presenting dendritic cells, generated some controversy regarding the ability of basophils to express MHC Class II molecules, present Ag and drive naïve T cell differentiation into Th2 cells. The focus of this review is to present the recent advances on the interactions between basophils and peripheral blood and tissue memory Th1, Th2, and Th17 cells, as well as their potential role in IgE-independent non-allergic chronic inflammatory disorders, including human inflammatory bowel diseases. Basophils interactions with the innate players of IgE-dependent allergic inflammation, particularly innate lymphoid cells, will also be considered. The previously unrecognized function for basophils in skewing adaptive immune responses opens novel perspectives for the understanding of their contribution to the pathogenesis of inflammatory diseases. PMID:26284078

  7. Extracellular inorganic phosphate regulates gibbon ape leukemia virus receptor-2/phosphate transporter mRNA expression in rat bone marrow stromal cells.

    PubMed

    Wada, Keinoshin; Mizuno, Morimichi; Komori, Takahide; Tamura, Masato

    2004-01-01

    In mammalian cells, several observations indicate not only that phosphate transport probably regulates local inorganic phosphate (Pi) concentration, but also that Pi affects normal cellular metabolism, which in turn regulates apoptosis and the process of mineralization. To elucidate how extracellular Pi regulates cellular functions of pre-osteoblastic cells, we investigated the expression of type III sodium (Na)-dependent Pi transporters in rat bone marrow stromal cells and ROB-C26 pre-osteoblastic cells. The mRNA expression level of gibbon ape leukemia virus receptor (Glvr)-2 was increased by the addition of Pi in rat bone marrow stromal cells, but not in ROB-C26 or normal rat kidney (NRK) cells. In contrast, the level of Glvr-1 mRNA was not altered by the addition of extracellular Pi in these cells. The induction of Glvr-2 mRNA by Pi was inhibited in the presence of cycloheximide (CHX). Moreover, mitogen-activated protein kinase (MEK) /extracellular-signal-regulated kinase (ERK) pathway inhibitors; U0126 (1.4-diamino-2, 3-dicyano-1, 4-bis [2-amino-phenylthio] butadiene) and PD98059 (2'-Amino-3'-methoxyflavone) inhibited inducible Glvr-2 mRNA expression, but p38 MEK inhibitor SB203580 [4-(4'-fluorophenyl)-2-(4'-methyl-sulfinylphenyl)-5-(4'pyridyl) imidazole] did not inhibit the induction of Glvr-2 mRNA expression, suggesting that extracellular Pi regulates de novo protein synthesis and MEK/ERK activity in rat bone marrow stromal cells, and through these, induction of Glvr-2 mRNA. Although Pi also induced osteopontin mRNA expression in rat bone marrow stromal cells but not in ROB-C26 and NRK cells, changes in cell viability with the addition of Pi were similar in both cell types. These data indicate that extracellular Pi regulates Glvr-2 mRNA expression, provide insights into possible mechanisms whereby Pi may regulate protein phosphorylation, and suggest a potential role for the Pi transporter in rat bone marrow stromal cells.

  8. Activation of Basophils Is a New and Sensitive Marker of Biocompatibility in Hemodialysis

    PubMed Central

    Aljadi, Zenib; Mansouri, Ladan; Nopp, Anna; Paulsson, Josefin M; Winqvist, Ola; Russom, Aman; Ståhl, Mårten; Hylander, Britta; Jacobson, Stefan H; Lundahl, Joachim

    2014-01-01

    The hemodialysis procedure involves contact between peripheral blood and the surface of dialyzer membranes, which may lead to alterations in the pathways of innate and adaptive immunity. We aimed to study the effect of blood–membrane interaction on human peripheral basophils and neutrophils in hemodialysis with high- and low-permeability polysulfone dialyzers. The surface expression of CD203c (basophil selection marker) and CD63 (activation marker) after activation by the bacterial peptide formyl-methionyl-leucyl-phenylalanine (fMLP) or anti-Fcε receptor I (FcεRI) antibody and the absolute number of basophils was investigated before and after hemodialysis with each of the dialyzers. Moreover, the expression on neutrophils of CD11b, the CD11b active epitope, and CD88 was analyzed in the same groups of individuals. The expression of CD63 in basophils following activation by fMLP was significantly higher in the patient group compared with that in healthy controls, but no differences were observed after activation by anti-FcεRI. During the hemodialysis procedure, the low-flux membrane induced up-regulation of CD63 expression on basophils, while passage through the high-flux membrane did not significantly alter the responsiveness. In addition, the absolute number of basophils was unchanged after hemodialysis with either of the dialyzers and compared with healthy controls. We found no significant differences in the expression of the neutrophil activation markers (CD11b, the active epitope of CD11b, and CD88) comparing the two different dialyzers before and after dialysis and healthy controls. Together, these findings suggest that alterations in basophil activity may be a useful marker of membrane bioincompatibility in hemodialysis. PMID:24712758

  9. Basophil phenotypes in chronic idiopathic urticaria in relation to disease activity and autoantibodies.

    PubMed

    Eckman, John A; Hamilton, Robert G; Gober, Laura M; Sterba, Patricia M; Saini, Sarbjit S

    2008-08-01

    Potentially pathogenic IgG autoantibodies to IgE or its receptor, Fc epsilonRIalpha, have been detected in approximately 40% of chronic idiopathic urticaria (CIU) patients. CIU patients' basophils display distinct altered Fc epsilonRIalpha-mediated degranulation. CIU patients with basophil histamine release in response to polyclonal goat anti-human IgE > or = 10% are classified as CIU responders (CIU-R) and < 10% are CIU non-responders (CIU-NR). We compared the presence of autoantibodies to basophil degranulation phenotypes and to disease status (active or inactive). Sera were collected from non-CIU subjects and CIU subjects who participated in a longitudinal study of disease severity and had defined basophil degranulation phenotypes. Immunoenzymetric assays (IEMA) quantified IgG anti-Fc epsilonRIalpha and anti-IgE. IgG anti-Fc epsilonRIalpha antibody was detected in 57% of CIU-R (n=35), 55% of CIU-NR (n=29), and 57% of non-CIU subjects (n=23), whereas IgG anti-IgE was present in 43% of CIU-R, 45% of CIU-NR, and 30% of non-CIU subjects. Both the autoantibody levels and the functional basophil phenotype remained stable in subjects with active disease (n=16), whereas there was an enhancement in basophil function as subjects evolved into a state of remission (n=6), which appears independent of the presence of autoantibody. IEMAs detected a similar frequency of autoantibodies in CIU-R, CIU-NR, and non-CIU subjects. Basophil function may be independent of IEMA-detected autoantibodies.

  10. Electron microscopic studies on human basophils from atopic and nonatopic subjects, using horse radish peroxidase labelled anti-IgE.

    PubMed

    van Elven, E H; Stallman, P J; Brühl, P C

    1977-01-01

    In previous studies, quantitative differences in cell-bound IgE on the basophils from various donors were measured by means of a quantitative immunofluorescence technique. In this study, cell-bound IgE was demonstrated on basophilic granulocytes by immunoelectron microscopy, using horse radish peroxidase labelled anti-IgE. The distribution of IgE on the basophils was studied in both atopic and nonatopic subjects. The intensity of the peroxidase staining on the basophils varied and appeared to correlate with the amount of cell-bound IgE, as estimated by quantitative immunofluorescence.

  11. Rat leucocyte response to the bites of rat fleas (Siphonaptera: Pulicidae).

    PubMed

    Vaughan, J A; Jerse, A E; Azad, A F

    1989-09-01

    The host response to bites of the oriental rat flea, Xenopyslla cheopis Rothschild, was investigated by examining rat blood leucocyte kinetics, histopathology, and the effect that the host response had upon subsequent flea feeding and longevity. Test rats were subjected to controlled exposures of fleas, and leucocyte data from test rats were compared to those of unexposed controls. Of the five leucocyte types examined, only the basophil appeared to play a role in the host blood response to flea bites. Significant increases in blood basophil levels occurred 2-3 d after exposure but subsided to control levels within a week. However, flea feeding did not produce histopathology at the flea feeding sites nor did the basophilic blood response of rats affect subsequent feeding or longevity of the fleas.

  12. Basophils are dispensable for the recovery of gross locomotion after spinal cord hemisection injury.

    PubMed

    Geurts, Nathalie; Vangansewinkel, Tim; Lemmens, Stefanie; Nelissen, Sofie; Geboes, Lies; Schwartz, Christian; Voehringer, David; Hendrix, Sven

    2016-04-01

    Basophils are the smallest population of granulocytes found in the circulation. They have crucial and nonredundant roles in allergic disorders, in protection from parasite infections, in autoimmunity, and in the regulation of type 2 immunity. They share phenotypic and functional properties with mast cells, which exert substantial protective effects after traumatic brain injury and spinal cord injury, although they are considered one of the most proinflammatory cell types in the body. In contrast, the in vivo functions of basophils in central nervous system trauma are still obscure and not well studied. In this study, we show that by comparing spinal cord injury in wild type vs. basophil-deficient Mcpt8Cre transgenic mice, the locomotor recovery is not affected in mice depleted in basophils. In addition, no substantial differences were observed in the lesion size and in the astrocytic and macrophage/microglia reaction between both mouse strains. Hence, despite the multiple properties shared with mast cells, these data show, for the first time, to our knowledge, that basophils are dispensable for the functional recovery process after hemisection injury to the spinal cord in mice.

  13. BASOPHILS AND THE T HELPER 2 ENVIRONMENT CAN PROMOTE THE DEVELOPMENT OF LUPUS NEPHRITIS

    PubMed Central

    Charles, Nicolas; Hardwick, Donna; Daugas, Eric; Illei, Gabor G.; Rivera, Juan

    2010-01-01

    Summary In systemic lupus erythematosus (SLE) self-reactive antibodies can target the kidney (lupus nephritis) leading to functional failure and possible mortality. We report that activation of basophils by autoreactive IgE, causes their homing to lymph nodes, promoting TH2 cell differentiation, and enhancing the production of self-reactive antibodies that cause lupus-like nephritis in Lyn−/− mice. SLE patients also have elevated serum IgE, self-reactive IgE's, and activated basophils that express CD62L and the MHC Class II molecule, HLA-DR; parameters that were found to be associated with increased disease activity and active lupus nephritis. Basophils were also present in the lymph nodes and spleen of SLE patients. Thus, in Lyn−/− mice, basophils and IgE autoantibodies amplify autoantibody production that leads to lupus nephritis, and in SLE patients, the presence of IgE autoantibodies and activated basophils are factors associated with disease activity and nephritis. PMID:20512127

  14. Impact of thermal processing and the Maillard reaction on the basophil activation of hazelnut allergic patients.

    PubMed

    Cucu, Tatiana; De Meulenaer, Bruno; Bridts, Chris; Devreese, Bart; Ebo, Didier

    2012-05-01

    Food allergy, an abnormal immunological response due to sensitization to a food component, has become an important health problem, especially in industrialized countries. The aim of this study was to investigate the impact of thermal processing and glycation on the basophil activation by hazelnut proteins using a basophil activation test. Patients with systemic allergic reactions (SR; n=6) to hazelnut as well as patients with an isolated oral allergy syndrome (OAS; n=4) were investigated. Thermal processing of hazelnut proteins either in the presence or absence of wheat proteins did not result in major changes in the stimulatory activity of the basophils for patients with SR or OAS. For the patients with OAS, incubation of hazelnut proteins with glucose led to complete depletion of the stimulatory activity of the basophils. An increase in stimulatory activity of the basophils for two out of six patients with SR was observed. For the other four patients slight or complete abolition of the stimulatory activity was observed. These results indicate that some patients with SR to hazelnut are at risk when exposed to hazelnut proteins, even in processed foods.

  15. Commensal bacterial–derived signals regulate basophil hematopoiesis and allergic inflammation

    PubMed Central

    Hill, David A.; Siracusa, Mark C.; Abt, Michael C.; Kim, Brian S.; Kobuley, Dmytro; Kubo, Masato; Kambayashi, Taku; LaRosa, David F.; Renner, Ellen D.; Orange, Jordan S.; Bushman, Frederic D.; Artis, David

    2012-01-01

    Commensal bacteria that colonize mammalian barrier surfaces are reported to influence T helper type 2 (TH2) cytokine–dependent inflammation and susceptibility to allergic disease, although the mechanisms that underlie these observations are poorly understood. In this report, we identify that deliberate alteration of commensal bacterial populations via oral antibiotic treatment resulted in elevated serum immunoglobulin E (IgE) levels, increased steady–state circulating basophil populations, and exaggerated basophil–mediated TH2 cell responses and allergic inflammation. Elevated serum IgE levels correlated with increased circulating basophil populations in mice and subjects with hyperimmunoglobulinemia E syndrome. Furthermore, B cell–intrinsic expression of MyD88 was required to limit serum IgE levels and circulating basophil populations in mice. Commensal–derived signals were found to influence basophil development by limiting proliferation of bone marrow–resident precursor populations. Collectively, these results identify a previously unrecognized pathway through which commensal–derived signals influence basophil hematopoiesis and susceptibility to TH2 cytokine–dependent inflammation and allergic disease. PMID:22447074

  16. The influence of commensal bacteria-derived signals on basophil-associated allergic inflammation

    PubMed Central

    Hill, David A.; Artis, David

    2013-01-01

    Commensal bacteria that colonize mammalian mucosal surfaces are reported to influence T helper type 2 (TH2) cytokine-dependent inflammation and susceptibility to allergic disease. However, the mechanisms that underlie these observations are only beginning to be understood. We recently utilized studies of murine model systems and atopic patient populations to elucidate a mechanism by which commensal bacteria-derived signals limit serum immunoglobulin E levels, influence basophil development and steady-state circulating basophil populations and regulate basophil-associated TH2 cell responses and allergic inflammation. In this addendum, we summarize the findings of our recent work and other developments in the field, discuss the broader implications of these findings and generate new hypotheses regarding our understanding of host-commensal relationships. These areas of investigation may be applicable to the development of new preventative or therapeutic approaches to reduce the burden of allergic disease. PMID:23137965

  17. The influence of commensal bacteria-derived signals on basophil-associated allergic inflammation.

    PubMed

    Hill, David A; Artis, David

    2013-01-01

    Commensal bacteria that colonize mammalian mucosal surfaces are reported to influence T helper type 2 (TH 2) cytokine-dependent inflammation and susceptibility to allergic disease. However, the mechanisms that underlie these observations are only beginning to be understood. We recently utilized studies of murine model systems and atopic patient populations to elucidate a mechanism by which commensal bacteria-derived signals limit serum immunoglobulin E levels, influence basophil development and steady-state circulating basophil populations and regulate basophil-associated TH 2 cell responses and allergic inflammation. In this addendum, we summarize the findings of our recent work and other developments in the field, discuss the broader implications of these findings and generate new hypotheses regarding our understanding of host-commensal relationships. These areas of investigation may be applicable to the development of new preventative or therapeutic approaches to reduce the burden of allergic disease.

  18. Basophil Activation Test identifies the patients with Chronic Spontaneous Urticaria suffering the most active disease

    PubMed Central

    Curto‐Barredo, Laia; Yelamos, Jose; Gimeno, Ramon; Mojal, Sergi; Pujol, Ramon M.

    2016-01-01

    Abstract Introduction The basophil activation test showing CD63 up regulation could be a specific and sensitive in vitro complementary text to the in vivo autologous serum skin test for the activity assessment of the patients suffering autoimmune chronic spontaneous urticaria. The aim of this study is to define the basophil activation test as a useful tool in clinical practice in order to identify those patients with more active disease. Methods We screened 139 patients (96 women) diagnosed of chronic spontaneous urticaria using simultaneously autologous serum skin test and basophil activation test and their relationship with disease activity. Results Positive autologous serum skin test was found in 56.8%; from them, 31.6% were basophil activation test positive. Negative autologous serum skin test result was found in the 43.2% of the sample that showed negative CD63 expression results in all cases, except one. Patients with positive autologous serum skin test and positive CD63 by basophil activation test showed significant higher Urticaria Activity Score of 7 days (P = 0.004) and of 3 weeks (P = 0.001) than patients with positive autologous serum skin test and negative CD63 (mean ± standard deviation [SD] 26.57 ± 10.56 versus 18.40 ± 12.05 for the Urticaria Activity Score of 7 days and 56.47 ± 23.78 versus 39.88 ± 25.44 for the Urticaria Activity Score of 3 weeks). Conclusions The CD63 expression on basophils appears as a reliable in vitro marker, useful in clinical practice in combination with autologous serum skin test to define chronic spontaneous urticaria patients with the highest urticaria activity that impairs a normal life. PMID:27980778

  19. Oxidative activity of ammonium persulfate salt on mast cells and basophils: implication in hairdressers' asthma.

    PubMed

    Pignatti, Patrizia; Frossi, Barbara; Pala, Gianni; Negri, Sara; Oman, Hans; Perfetti, Luca; Pucillo, Carlo; Imbriani, Marcello; Moscato, Gianna

    2013-01-01

    Persulfate salts are components of bleaching powders widely used by hairdressers during hair-bleaching procedures. Hairdressers are at high risk for occupational asthma and rhinitis, and ammonium persulfate is the main etiologic agent. To explore the effects of ammonium persulfate on human albumin, mast cells, and basophils in order to evaluate a possible effect of ammonium persulfate oxidizing activity in the mechanism of ammonium persulfate-induced occupational asthma. High-performance liquid chromatography/mass spectrometry was performed on ammonium persulfate-incubated human albumin. The activation of LAD2 human mast cell and KU812 human basophil cell lines incubated with ammonium persulfate was evaluated. CD63 expression on persulfate-in-vitro-incubated blood basophils from nonexposed healthy controls (n = 31) and hairdressers with work-related respiratory symptoms (n = 29) was assessed by flow cytometry. No persulfate-albumin conjugate was found. An oxidative process on tryptophan and methionine was detected. Ammonium persulfate induced reactive oxygen species (ROS) generation and the degranulation of LAD2 and KU812 cells. Human basophils from healthy controls, incubated in vitro with ammonium persulfate, showed increased CD63 expression and ROS production. In hairdressers with ammonium persulfate-caused occupational asthma (positive persulfate challenge), basophil-CD63 expression was higher than in those with a negative challenge and in healthy controls. Ammonium persulfate incubated with human albumin did not generate any adduct but oxidized some amino acids. This oxidizing activity induced human mast cell and basophil activation which might be crucial in the mechanism of persulfate-induced occupational asthma and rhinitis. Copyright © 2012 S. Karger AG, Basel.

  20. Novel basophil- or eosinophil-depleted mouse models for functional analyses of allergic inflammation.

    PubMed

    Matsuoka, Kunie; Shitara, Hiroshi; Taya, Choji; Kohno, Kenji; Kikkawa, Yoshiaki; Yonekawa, Hiromichi

    2013-01-01

    Basophils and eosinophils play important roles in various host defense mechanisms but also act as harmful effectors in allergic disorders. We generated novel basophil- and eosinophil-depletion mouse models by introducing the human diphtheria toxin (DT) receptor gene under the control of the mouse CD203c and the eosinophil peroxidase promoter, respectively, to study the critical roles of these cells in the immunological response. These mice exhibited selective depletion of the target cells upon DT administration. In the basophil-depletion model, DT administration attenuated a drop in body temperature in IgG-mediated systemic anaphylaxis in a dose-dependent manner and almost completely abolished the development of ear swelling in IgE-mediated chronic allergic inflammation (IgE-CAI), a typical skin swelling reaction with massive eosinophil infiltration. In contrast, in the eosinophil-depletion model, DT administration ameliorated the ear swelling in IgE-CAI whether DT was administered before, simultaneously, or after, antigen challenge, with significantly lower numbers of eosinophils infiltrating into the swelling site. These results confirm that basophils and eosinophils act as the initiator and the effector, respectively, in IgE-CAI. In addition, antibody array analysis suggested that eotaxin-2 is a principal chemokine that attracts proinflammatory cells, leading to chronic allergic inflammation. Thus, the two mouse models established in this study are potentially useful and powerful tools for studying the in vivo roles of basophils and eosinophils. The combination of basophil- and eosinophil-depletion mouse models provides a new approach to understanding the complicated mechanism of allergic inflammation in conditions such as atopic dermatitis and asthma.

  1. /sup 3/H arachidonic acid incorporation and metabolism in purified human basophils

    SciTech Connect

    Warner, J.A.; Peters, S.P.; Lichtenstein, L.M.; MacGlashan, D.W. Jr.

    1986-03-01

    A central feature of the allergic response is the generation of arachidonic acid (AA) metabolites by basophils and mast cells. In addition, AA metabolism may play a role in regulating the anti-IgE mediated degranulation of human basophils. To study this biochemistry, purified human basophils (>80%) were labeled with /sup 3/H-AA (0.3 ..mu..M, 25 ..mu..Ci/ml, 2 hours at 37/sup 0/C) and subsequently challenged with anti-IgE. Basophils were found to incorporate 45 +/- 3% of the exogenous AA which distributed into phospholipids (PL) (77.1 +/- 3.5%) and neutral lipids (19.7 +/- 3.3%) with only 5.3 +/- 2.7% remaining as the free acid (n = 7). Phosphatidylcholine (23.9 +/- 1.7%), phosphatidylinositol (22.0 +/- 1.4%) and phosphatidylethanolamine (14.5 +/- 2.7%) accounted for the majority of the AA with the remaining PL containing <3%. Anti-IgE (0.1 ..mu..g/ml) challenge led to the release of histamine (23.8 +/- 4.7%) and /sup 3/H-AA (8.1 +/- 1.7%) (n = 5). HPLC analysis revealed unmetabolized /sup 3/H-AA, /sup 3/H-LTC/sub 4/, /sup 3/H-HETE and an unidentified peak which migrated in the prostaglandin region of the elution profile. The same metabolites were released when the basophils were challenged with antigen. The calcium ionophore A23187 (1..mu..g/ml) also caused the release of histamine (37.4 +/- 4.1%) and /sup 3/H-AA (17.0 +/- 2.9%), while the phorbol ester, TPA caused HR (19.7 +/- 5.8%) but no increase in /sup 3/H AA turnover. Because of limited cell numbers this is the first time the authors have been able to study AA metabolism in human basophils.

  2. ANTIGENS OF LEUKEMIAS INDUCED BY NATURALLY OCCURRING MURINE LEUKEMIA VIRUS: THEIR RELATION TO THE ANTIGENS OF GROSS VIRUS AND OTHER MURINE LEUKEMIA VIRUSES

    PubMed Central

    Geering, Gayla; Old, Lloyd J.; Boyse, Edward A.

    1966-01-01

    Leukemias can be induced in W/Fu inbred rats by neonatal inoculation of normal thymus cells of C58 mice. These leukemias are not transplantable to C58 mice or to adult W/Fu rats, but they can be kept in passage in W/Fu rats aged 0 to 7 days. Adult W/Fu rats inoculated repeatedly with these isogenic leukemias produce cytotoxic and precipitating antibodies. These antisera are of particular value in the analysis of the antigens of leukemia cells and of leukemia viruses because their mode of preparation precludes the formation of antibody against any normal constituents of the cell. Analysis based on the cytotoxic test indicates the presence of 2 distinct cell surface antigens in leukemias induced by Passage A Gross virus or occurring spontaneously in mice of high-incidence strains. All leukemias and other tissues known to contain G (Gross) leukemia antigen have both determinants, but certain leukemias of low-incidence strains have only 1 of them and so were previously classified G-. Immunoprecipitation with these antisera reveals the presence of a cellular antigen common to G+ cells and absent from G- cells; the same antigen can be demonstrated in ether-treated Gross virus, but not in intact virus. This antigen is present also in ether-treated preparations of the Friend, Moloney, and Rauscher leukemia viruses, but not in Bittner (mammary tumor) virus. Thus it may be regarded as a group-specific antigen of murine leukemia viruses, in contrast to the type-specific cellular antigens demonstrable by the cytotoxic test. Four additional antigens associated with leukemias induced by wild-type Gross virus have been demonstrated by immunoprecipitation, but their relation to viral and cellular antigens has not been determined. PMID:4288480

  3. L3L4ES antigen and secretagogues induce histamine release from porcine peripheral blood basophils after Ascaris suum infection

    USDA-ARS?s Scientific Manuscript database

    The aim of this paper was to investigate the role of porcine basophils in protective immunity. Experimental pigs were infected with 1,000 Ascaris suum eggs daily for 21 days. Control pigs were maintained helminth-free. Circulating porcine basophils were isolated from the anti-coagulated whole blood ...

  4. α(1,3) Fucosyltransferases IV and VII are essential for the initial recruitment of basophils in chronic allergic inflammation.

    PubMed

    Saeki, Kazumi; Satoh, Takahiro; Yokozeki, Hiroo

    2013-09-01

    Basophils act as initiator cells for the development of IgE-mediated chronic allergic inflammation (IgE-CAI). However, detailed mechanisms of initial recruitment of basophils into the skin have yet to be clarified. Selectins mediate leukocyte capture and rolling on the vascular endothelium for extravasation. Counter-receptor activity of selectins is regulated by α(1, 3) fucosyltransferases (FTs) IV and VII. To clarify the contribution of selectin ligands regulated by FTs for initial basophil recruitment, IgE-CAI was induced in mice deficient in FT-IV and/or FT-VII genes. Although FT-IV(-/-) and FT-VII(-/-) mice exhibited comparable skin responses to wild-type mice, the FT-IV(-/-)/FT-VII(-/-) mice showed significantly impaired inflammation. Although the transfer of basophils to FcRγ(-/-) mice induced IgE-CAI, this induction was completely absent when basophils from FT-IV(-/-)/FT-VII(-/-) mice were transferred. L-selectin, but not P- and E-selectin, blocking Abs inhibited skin inflammation in vivo. P-selectin glycoprotein-1 (PSGL-1) antibody also ameliorated skin inflammation, and basophils were bound to L-selectin in a PSGL-1-dependent manner, which was regulated by FT-IV/VII. Functional PSGL-1 generated by basophil FT-IV/VII and its subsequent binding to L-selectin could be one of the essential steps required for initial basophil recruitment and the development of IgE-CAI in mice.

  5. Potato lectin activates basophils and mast cells of atopic subjects by its interaction with core chitobiose of cell-bound non-specific immunoglobulin E

    PubMed Central

    Pramod, S N; Venkatesh, Y P; Mahesh, P A

    2007-01-01

    A major factor in non-allergic food hypersensitivity could be the interaction of dietary lectins with mast cells and basophils. Because immunoglobulin E (IgE) contains 10–12% carbohydrates, lectins can activate and degranulate these cells by cross-linking the glycans of cell-bound IgE. The present objective focuses on the effect of potato lectin (Solanum tuberosum agglutinin; STA) for its ability to release histamine from basophils in vitro and mast cells in vivo from non-atopic and atopic subjects. In this study, subjects were selected randomly based on case history and skin prick test responses with food, pollen and house dust mite extracts. Skin prick test (SPT) was performed with STA at 100 µg/ml concentration. Histamine release was performed using leucocytes from non-atopic and atopic subjects and rat peritoneal exudate cells. SPT on 110 atopic subjects using STA showed 39 subjects positive (35%); however, none showed STA-specific IgE; among 20 non-atopic subjects, none were positive by SPT. Maximal histamine release was found to be 65% in atopic subjects (n = 7) compared to 28% in non-atopic subjects (n = 5); the release was inhibited specifically by oligomers of N-acetylglucosamine and correlates well with serum total IgE levels (R2 = 0·923). Binding of STA to N-linked glycoproteins (horseradish peroxidase, avidin and IgG) was positive by dot blot and binding assay. As potato lectin activates and degranulates both mast cells and basophils by interacting with the chitobiose core of IgE glycans, higher intake of potato may increase the clinical symptoms as a result of non-allergic food hypersensitivity in atopic subjects. PMID:17362264

  6. Understanding Leukemia

    MedlinePlus

    ... a microscope. Bone marrow biopsy I A very small amount of bone filled with marrow cells is removed through a needle. The cells are then looked at under a microscope. Each main type of leukemia also has different subtypes . In other words, patients ...

  7. Childhood Cancer: Leukemia (For Parents)

    MedlinePlus

    ... acute. Acute childhood leukemias are also divided into acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) , depending on ... Bone Marrow Childhood Cancer Neutropenia Stem Cell Transplants Acute Lymphoblastic Leukemia (ALL) Chemotherapy Radiation Therapy Chronic Myelogenous Leukemia (CML) ...

  8. Chronic Myelogenous Leukemia

    MedlinePlus

    Chronic myelogenous leukemia Overview Chronic myelogenous leukemia (CML) is an uncommon type of cancer of the blood cells. The term "chronic" in chronic myelogenous leukemia indicates that this cancer ...

  9. Fluvastatin Suppresses Mast Cell and Basophil IgE Responses: Genotype-Dependent Effects

    PubMed Central

    Kolawole, Elizabeth Motunrayo; McLeod, Jamie Josephine Avila; Ndaw, Victor; Abebayehu, Daniel; Barnstein, Brian O.; Faber, Travis; Spence, Andrew J.; Taruselli, Marcela; Paranjape, Anuya; Haque, Tamara T.; Qayum, Amina Abdul; Wijesinghe, Dayanjan S.; Sturgill, Jamie L.; Chalfant, Charles E.; Straus, David B.; Oskeritzian, Carole A.; Ryan, John J.

    2015-01-01

    Mast cell- and basophil-associated inflammatory diseases are a considerable burden to society. A significant portion of patients have symptoms despite standard-of-care therapy. Statins, used to lower serum cholesterol, have immune modulating activities. We tested the in vitro and in vivo effects of statins on IgE-mediated mast cell and basophil activation. Fluvastatin showed the most significant inhibitory effects of the six statins tested, suppressing IgE-induced cytokine secretion among mouse mast cells and basophils. Fluvastatin's effects were reversed by mevalonic acid or geranylgeranyl pyrophosphatase, and mimicked by geranylgeranyl transferase inhibition. Fluvastatin selectively suppressed key FcεRI signaling pathways, including Syk, Akt, and ERK. While mast cells and basophils from the C57BL/6J mouse strain were responsive to fluvastatin, those from 129/SvImJ mice were completely resistant. Resistance correlated with fluvastatin-induced upregulation of the statin target HMG-CoA reductase. Human mast cell cultures from eight donors showed a wide range of fluvastatin responsiveness. These data demonstrate that fluvastatin is a potent suppressor of IgE-mediated mast cell activation, acting at least partly via blockade of geranyl lipid production downstream of HMG-CoA reductase. Importantly, consideration of statin use for treating mast cell-associated disease needs to incorporate genetic background effects, which can yield drug resistance. PMID:26773154

  10. Reduced Venous Blood Basophil Count and Anxious Depression in Patients with Major Depressive Disorder

    PubMed Central

    Baek, Ji Hyun; Kim, Hee-Jin; Fava, Maurizio; Mischoulon, David; Papakostas, George I; Nierenberg, Andrew; Heo, Jung-Yoon

    2016-01-01

    Objective Anxious depression has a distinct neurobiology, clinical course and treatment response from non-anxious depression. Role of inflammation in anxious depression has not been examined. As an exploratory study to characterize the role of inflammation on a development of anxious depression, we aimed to determine the relationship between white blood cell (WBC) subset counts and anxiety in individuals with major depressive disorder (MDD). Methods A total of 709 patients who were newly diagnosed with MDD were recruited. Anxiety levels of participants were evaluated using the Anxiety/ Somatization subitem of the Hamilton Depression Rating Scale. The association between WBC subset fraction and anxiety was evaluated. Results Basophil and eosinophil sub-fractions showed significant negative correlations with HAM-D anxiety/somatization factor scores (basophils: r=-0.092, p=0.014 and eosinophils: r=-0.075, p=0.046). When an anxiety score (a sum of somatic and psychic anxiety) was entered as a dependent variable, only basophils showed significant negative association with the anxiety scores after adjusting for all other WBC subset counts and demographic factors (t=-2.57, p=0.010). Conclusion This study showed that anxious depression had a decreased basophil subfraction, which might be associated with involvement of inflammation in development of anxious depression. PMID:27247599

  11. Influence of bronchial allergen challenge on histamine release by human basophils.

    PubMed

    Lie, W J; Van Der Veen, M J; Knol, E F; Mul, F P; Jansen, H M; Roos, D; Van Der Zee, J S

    2000-06-01

    Basophils can be primed by cytokines such as interleukin (IL) -3, IL-5 or granulocyte macrophage-colony stimulating factor (GM-CSF). It has been described that the concentrations of these cytokines are enhanced at sites of allergic inflammation as well as systemic in allergic asthma. To investigate the priming status of basophils as detected by thapsigargin-induced histamine release during bronchial allergen challenge. Ten subjects allergic to house dust mite were challenged via an aerosol delivery system. Spontaneous leucocyte histamine release as well as histamine release induced by various stimuli was measured in vitro at several time points. In addition, lung function parameters, serum IL-5 and blood eosinophil counts were evaluated. We found no effect of bronchial allergen challenge upon spontaneous leucocyte histamine release, nor upon histamine release induced by anti-immunoglobulin (Ig) E, house dust mite extract, C5a, fMLP, IL-3, PMA+ thapsigargin or IL-3+ thapsigargin. However, the priming status of basophils as measured by thapsigargin-induced histamine release was enhanced at 24 h after bronchial allergen challenge. Analysis of the individual data showed a heterogeneous initial response (30 min, 6 h) followed by a predominant increase at 24 h after allergen challenge. This increase in the thapsigargin-induced histamine release correlated with the increase in serum IL-5 levels at 24 h after allergen challenge. The priming status of human basophils as measured by thapsigargin-induced histamine release is enhanced 24 h after allergen challenge.

  12. Simultaneous initiation of degranulation and inhibition of leukotriene release by soman in human basophils

    SciTech Connect

    Meier, H.L.; Warner, J.; MacGlashan, D.W.

    1995-12-31

    Previous studies noted that the serine esterase inhibitor, soman, could induce histamine release from human basophils. To investigate the mechanisms by which soman causes histamine release (a preformed mediator), we also examined its ability to induce leukotriene release (a newly synthesized mediator) from basophils. We found that no leukotriene release followed activation with soman, while histamine release was usually greater than 70%. In addition, soman and diisopropyl-fluorophosphate were found actively to suppress low level spontaneous leukotriene release as well as ongoing leukotriene release induced by anti-IgE antibody. Soman (0.3 mM) was able to stop leukotriene release as rapidly as the calcium chelator, EDTA. In a series of control experiments, it was noted that soman did not influence the metabolism of LTC4 to LTD4 or LTE4 (for which little metabolism occurred), eliminating the possibility that reduced LTC4 release could have resulted from its enhanced metabolism. Therefore, using one compound (soman), basophils could be simultaneously activated to degranulate while having the pathway leading to leukotriene release actively suppressed. These results provide further evidence that histamine and leukotriene release are independent pathways resulting from the activation of basophils.

  13. In vitro immunological degranulation of human basophils is modulated by lung histamine and Apis mellifica.

    PubMed Central

    Poitevin, B; Davenas, E; Benveniste, J

    1988-01-01

    1. The effect of high dilutions of two homeopathic drugs Lung histamine (Lung his) and Apis mellifica (Apis mel) used for the treatment of allergic diseases has been assessed on in vitro human basophil degranulation. Experiments were conducted blind. 2. Basophil degranulation induced by 1.66 X 10(-9) M anti-IgE antibody was significantly inhibited in the presence of 5 Lung his (5th centesimal dilution of Lung his) and 15 Lung his (15th centesimal dilution of Lung his) by 28.8% and 28.6% respectively and by 65.8% in the presence of 9 Apis mel (9th centesimal dilution of Apis mel). Basophil degranulation induced by 1.66 X 10(-16) to 1.66 X 10(-18) M anti-IgE antibody was also inhibited by high dilutions of Lung his and Apis mel with an inhibition of nearly 100% with 18 Lung his (18th centesimal dilution of Lung his) and 10 Apis mel (10th centesimal dilution of Apis mel). An alternance of inhibition, inactivity and stimulation was observed when basophils were incubated in the presence of serial dilutions of Lung his and Apis mel. 3. The investigation of the clinical efficacy of high dilutions of Lung his and Apis mel should be envisaged in allergic diseases in parallel with in vitro and ex vivo biological assays. PMID:3382588

  14. Sequential allergen desensitization of basophils is non-specific and may involve p38 MAPK.

    PubMed

    Witting Christensen, S K; Kortekaas Krohn, I; Thuraiaiyah, J; Skjold, T; Schmid, J M; Hoffmann, H J H

    2014-10-01

    Sequential allergen desensitization provides temporary tolerance for allergic patients. We adapted a clinical protocol to desensitize human blood basophils ex vivo and investigated the mechanism and allergen specificity. We included 28 adult, grass allergic subjects. The optimal, activating allergen concentration was determined by measuring activated CD63(+) CD193(+) SS(Low) basophils in a basophil activation test with 8 log-dilutions of grass allergen. Basophils in whole blood were desensitized by incubation with twofold to 2.5-fold increasing allergen doses in 10 steps starting at 1 : 1000 of the optimal dose. Involvement of p38 mitogen-activated protein kinase (MAPK) was assessed after 3 min of allergen stimulation (n = 7). Allergen specificity was investigated by desensitizing cells from multi-allergic subjects with grass allergen and challenging with optimal doses of grass, birch, recombinant house dust mite (rDer p2) allergen or anti-IgE (n = 10). Desensitization reduced the fraction of blood basophils responding to challenge with an optimal allergen dose from a median (IQR) 81.0% (66.3-88.8) to 35.4% (19.8-47.1, P < 0.0001). CD63 MFI expression was reduced from 68 248 (29 336-92 001) to 30 496 (14 046-46 179, P < 0.0001). Basophils from multi-allergic subjects were desensitized with grass allergen. Challenge with grass allergen resulted in 39.6% activation (15.8-58.3). An unrelated challenge (birch, rDer p2 or anti-IgE) resulted in 53.4% activation (30.8-66.8, P = 0.16 compared with grass). Desensitization reduced p38 MAPK phosphorylation from a median 48.1% (15.6-92.8) to 26.1% (7.4-71.2, P = 0.047) and correlated with decrease in CD63 upregulation (n = 7, r > 0.79, P < 0.05). Desensitization attenuated basophil response rapidly and non-specifically at a stage before p38 MAPK phosphorylation. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Basophil mediated pro-allergic inflammation in vehicle-emitted particles exposure.

    PubMed

    Zakharenko, Alexander M; Engin, Ayse Basak; Chernyshev, Valery V; Chaika, Vladimir V; Ugay, Sergey M; Rezaee, Ramin; Karimi, Gholamreza; Drozd, Vladimir A; Nikitina, Anna V; Solomennik, Sergey F; Kudryavkina, Olga R; Xin, Liu; Wenpeng, Yuan; Tzatzarakis, Manolis; Tsatsakis, Aristidis M; Golokhvast, Kirill S

    2017-01-01

    Despite of the fact that engine manufacturers develop a new technology to reduce exhaust emissions, insufficient attention given to particulate emissions. However, diesel exhaust particles are a major source of air-borne pollution, contain vast amount of polycyclic aromatic hydrocarbons (PAHs) and may have deleterious effects on the immune system, resulting in the induction and enhancement of pro-allergic processes. In the current study, vehicle emitted particles (VEP) from 2 different types of cars (diesel - D and gasoline - G) and locomotive (L) were collected. Overall, 129 four-week-old, male SPF-class Kunming mice were subcutaneously instilled with either low dose 100, 250 or high dose, 500mg/kg VEP and 15 mice were assigned as control group. The systemic toxicity was evaluated and alterations in the percentages of the CD3, CD4, CD8, CD16, CD25 expressing cells, basophils, eosinophils and neutrophils were determined. Basophil percentages were inversely associated with the PAH content of the VEPs, however basophil sensitization was more important than cell count in VEP exposure. Thus, the effects of VEP-PAHs emerge with the activation of basophils in an allergen independent fashion. Despite the increased percentage of CD4+ T cells, a sharp decrease in basophil counts at 500mg/kg of VEP indicates a decreased inhibitory effect of CD16+ monocytes on the proliferation of CD4+ T cell and suppressed polarization into a Th2 phenotype. Therefore, although the restrictions for vehicles emissions differ between countries, follow up studies and strict regulations are needed. Copyright © 2016 Elsevier Inc. All rights reserved.

  16. Listeria infection inhibits IgE production in regional lymph nodes by suppressing chemotaxis of basophils to lymph nodes.

    PubMed

    Kanoh, Makoto; Maruyama, Saho; Asano, Yoshihiro

    2013-12-01

    Infection with Listeria induces a dominant shift to the Th1 immune response and inhibits the Th2 response. Papain is frequently utilized in animal models of allergies. Papain administration induces chemotaxis of basophils to regional lymph nodes (LNs) and production of interleukin (IL)-4 by basophils, resulting in a Th2-dominant status and increased IgE production in LNs. In this model, production of immunoglobulin (Ig) E by LN cells is primarily controlled by IL-4 produced by basophils. Based on this model, it was postulated that Listeria monocytogenes (Lm) infection suppresses IgE production by LN cells. Therefore, the effects of Lm infection on a papain-induced mouse model of allergies were investigated. Following s.c. injection of papain, basophils transiently migrated to draining LNs because of the effects of chemokine (C-C) motif ligand (CCL) 24 and secreted IL-4, inducing a Th2 response. Lm infection blocked recruitment of basophils into the popliteal LNs by inhibiting CCL24 production. Papain-induced class switch recombination (CSR) to IgE is inhibited by Lm infection, whereas CSR to IgG1 is not affected by the same treatment. Therefore, the CSR of IgG1 to IgE is basophil-dependent, whereas the CSR of IgM to IgG1 is basophil-independent. Hence, Lm infection suppresses CSR to IgE without affecting CSR to IgG1.

  17. IgE and IL-33-mediated triggering of human basophils inhibits TLR4-induced monocyte activation.

    PubMed

    Rivellese, Felice; Suurmond, Jolien; de Paulis, Amato; Marone, Gianni; Huizinga, Tom W J; Toes, René E M

    2014-10-01

    Basophils are circulating granulocytes, best known as effector cells in allergic reactions. Recent studies in mice suggest that they might also participate in the suppression of chronic inflammation. The aim of this study was to assess the ability of purified human basophils to modulate monocyte responses upon IL-33 and IgE triggering. Activation of human basophils with IL-33 induced the production of IL-4 and the release of histamine, and enhanced their IgE-mediated activation. In addition, basophils triggered with IL-33 and anti-IgE significantly suppressed the LPS-induced production of the proinflammatory cytokine TNF-α and the upregulation of the costimulatory molecule CD80 by monocytes. These effects were mainly explained by the release of histamine, as they could be inhibited by the histamine receptor 2 antagonist ranitidine, with a smaller contribution of IL-4. In contrast, basophil-derived IL-4 and histamine had opposing effects on the expression of the inhibitory Fc γ receptor IIb and the production of IL-10 by monocytes. Our data show that basophils can influence monocyte activation and suggest a previously unrecognized role for human basophils in the modulation of monocyte-mediated immune responses, through the balanced secretion of histamine and IL-4.

  18. Ghrelin and obestatin promote the allergic action in rat peritoneal mast cells as basic secretagogues.

    PubMed

    Hirayama, Tatsuya; Kawabe, Tsutomu; Matsushima, Miyoko; Nishimura, Yuko; Kobe, Yuko; Ota, Yui; Baba, Kenji; Takagi, Kenzo

    2010-11-01

    Ghrelin is an endogenous ligand of the type 1a growth hormone secretagogue receptor (GHSR1a) that regulates energy balance. Ghrelin and obestatin, derived from the post-translational processing of preproghrelin, are involved in a diverse range of biological activities, yet their effect on the immune system is not fully understood. In the present study, we investigated the roles of ghrelin and obestatin on mast cell degranulation and found that both ghrelin and obestatin induce the release of histamine from rat peritoneal mast cells. This induced histamine release was inhibited by the pertussis toxin, an inhibitor of Gα(i) protein, and extracellular Ca(2+). Rat peritoneal mast cells and rat basophilic leukemia (RBL-2H3) cells did not express the ghrelin receptor GHSR1a, suggesting that histamine release induced by ghrelin occurs via a receptor-independent mechanism. We report here that ghrelin and obestatin, belonging to the family of basic secretagogues, stimulate mast cells independent of a receptor, and this may play a crucial role at the site of allergy or inflammation.

  19. Metastatic Calcinosis Cutis: A Case in a Child with Acute Pre-B Cell Lymphoblastic Leukemia

    PubMed Central

    Castanedo-Cázares, Juan Pablo; Reyes-Herrera, Amalia; Hernández-Blanco, Diana; Oros-Ovalle, Cuauhtémoc; Torres-Álvarez, Bertha

    2015-01-01

    Hypercalcemia in children with malignancy is an uncommon condition. It has been described in leukemia patients with impaired renal excretion of calcium or osteolytic lesions. Metastatic calcinosis cutis (MCC) may develop if hypercalcemia persists. We report the case of a 5-year-old girl with an atypical dermatosis and unspecific gastrointestinal symptoms. Considered clinical diagnoses were xanthomas, histiocytosis, molluscum contagiosum, and nongenital warts. Cutaneous histological analysis showed amorphous basophilic deposits in the dermis suggestive of calcium deposits. Laboratory tests confirmed serum hypercalcemia. Extensive investigations such as bone marrow biopsy established the diagnosis of an acute pre-B cell lymphoblastic leukemia. Hypercalcemia in hematopoietic malignancies is unusual, especially as initial manifestation of the disease. Careful review of the literature fails to reveal previous reports of these peculiar cutaneous lesions of MCC in children with leukemia. PMID:26346120

  20. Leukemia revisited

    SciTech Connect

    Cronkite, E P

    1980-01-01

    Selected features of the historical development of our knowledge of leukemia are discussed. The use of different methodologies for study of the nature of leukemic cell proliferation are analyzed. The differences between older cell kinetic data using tritiated thymidine and autoradiography and the newer cell culture methods are more apparent than real. It is suggested that tritiated thymidine and extracorporeal irradiation of the blood may be useful for therapeutic agents that have not been given an adequate trial. Radiation leukemogenesis presents an opportunity for study of the nature of leukemogenesis that has not been exploited adequately.

  1. The leukemias: Epidemiologic aspects

    SciTech Connect

    Linet, M.S.

    1984-01-01

    Particularly geared to physicians and cancer researchers, this study of the epidemiology and etiology of leukemia analyzes the four major leukemia subtypes in terms of genetic and familial determinant factors and examines the incidence, distribution and frequency of reported leukemia clusters. Linet discusses the connection between other types of malignancies, their treatments, and the subsequent development of leukemia and evaluates the impact on leukemia onset of such environmental factors as radiation therapy, drugs, and occupational hazards.

  2. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  3. [Analysis and differentiation of cytergic immune reactions: tuberculine type and cutaneous basophilic hypersensitivity (author's transl)].

    PubMed

    Günther, O

    1975-07-01

    The classic delayed tuberculine reaction represents a T-cell mediated immune reaction, detectable already before the formation of antibodies in the course of proteine sensitization. Myocobacteria stimulate and enhance this reaction. The skin test reaction needs the whole antigen for induction. The reaction starts 6 to 8 hours later, shows maximal development 24 to 28 (-72) hours later and is characterized by inflammation, induration, sometimes with hemorrhagies, necroses and ulceration, a macrophage infiltration is typical in the histological picture. During the reaction between antigen and sensitized T-cells mediators are set free which act by the way of unspecific stimulation on T-, B-lymphocytes and macrophages, otherwise they may inhibit macrophage migration. The delayed reaction is active in many infectious diseases and in the rejection of transplants and tumours. The cutaneous basophilic hypersensitivity (Jones-Mote) is a T-cell mediated immune reaction, detectable even before the classic delayed reaction after sensitization with tiny up to large doses of proteines. The skin reaction needs the whole antigen for induction, is visible 2 to 4 hours later in form of an inflammation with slight swelling and reaches maximal development 12 to 24 hours later without hemorrhagies or necroses. The infiltration consists mainly of basophilic leucocytes. There exists a weaker avidity of the T-cells of the cutaneous basophilic hypersensitivity compared to the T-cells of the delayed reaction or to the amount of antibodies. Therefore this reaction is easily suppressed by other immune reactions. In contactdermatitis and vaccine virus infections of the guinea pig the cutaneous basophilic hypersensitivity consists for weeks and months because under these circumstances other immune reactions do not compete. The differentiation of the two reactions shall develop to a routine laboratory procedure due to their therapeutic consequences in the immune diagnostic field.

  4. Short-, Intermediate-, and Long-Term Changes in Basophil Reactivity Induced by Venom Immunotherapy

    PubMed Central

    Cámara Hijón, Carmen; Ramos Cantariño, Alfonso; Romero-Chala, Silvia; García-Trujillo, José Antonio; Fernández Pereira, Luis Miguel

    2016-01-01

    Purpose The basophil activation test (BAT) has been used to monitor venom immunotherapy (VIT) due to its high specificity. A previous study has reported a good correlation between a significant decrease in basophil activation during 5 years of VIT and clinical protection assessed by sting challenge. The following prospective study was performed to examine changes in basophil reactivity over a complete VIT period of 5 years. Methods BAT in a dose-response curve was studied prospectively in 10 hymenoptera venom-allergic patients over 5 years of VIT. BAT was performed at the time of diagnosis, 1 month after finishing the VIT build-up phase, and 3, 6, 12, 24, and 60 months after beginning treatment. The repeated measures ANOVA was applied to evaluate basophil activation changes throughout VIT. A cross-sectional study was also performed in 6 patients who received treatment for more than 3 years, and in another 12 patients who followed immunotherapy for at least 5 years. Results An early activation decrease was observed during the first 3 months of treatment, compared to pre-treatment values. This activation decrease was not maintained 6 to 18 months after treatment, but was observed again after 2 years of treatment, and maintained until the completion of the 5-year immunotherapy period. In cross-sectional analysis, the 6 patients who received treatment for 3 years, and 9 of the 12 patients who received treatment for 5 years, had negative BAT results. Three patients in this last group had positive BAT results and 2 patients had systemic reactions after field stings. Conclusions BAT appears to be an optimal non-invasive test for close monitoring of VIT. PMID:27334779

  5. Childhood Cancer: Leukemia (For Parents)

    MedlinePlus

    ... Habits for TV, Video Games, and the Internet Leukemia KidsHealth > For Parents > Leukemia Print A A A ... Causes Symptoms Diagnosis Treatment en español Leucemia About Leukemia The term leukemia refers to cancers of the ...

  6. What Is Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells in the body begin ... the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts in the ...

  7. What Is Chronic Myeloid Leukemia?

    MedlinePlus

    ... About Chronic Myeloid Leukemia What Is Chronic Myeloid Leukemia? Cancer starts when cells in the body begin ... is the same as for adults. What is leukemia? Leukemia is a cancer that starts in the ...

  8. Basophil-associated OX40 Ligand Participates in the Initiation of Th2 Responses during Airway Inflammation*

    PubMed Central

    Di, Caixia; Lin, Xiaoliang; Zhang, Yanjie; Zhong, Wenwei; Yuan, Yufan; Zhou, Tong; Liu, Junling; Xia, Zhenwei

    2015-01-01

    Asthma is characterized by increased airway submucosal infiltration of T helper (Th) cells and myeloid cells that co-conspire to sustain a chronic inflammation. While recent studies have demonstrated that the myeloid basophils promote Th2 cells in response to various types of allergens, the underlying mechanisms are poorly understood. Here, we found for the first time that in a mouse model of allergic asthma basophils highly expressed OX40 ligand (OX40L) after activation. Interestingly, blockade of OX40-OX40L interaction suppressed basophils-primed Th2 cell differentiation in vitro and ameliorated ovalbumin (OVA)-induced allergic eosinophilic inflammation mediated by Th2 activation. In accordance, the adoptive transfer of basophils derived from mediastinal lymph nodes (MLN) of OVA-immunized mice triggered a robust Th2 response and eosinophilic inflammation in wild-type mice but largely muted in OX40−/− mice and mice receiving OX40L-blocked basophils. Taken together, our results reveal a critical role of OX40L presented by the activated basophils to initiate Th2 responses in an allergic asthma model, implicating OX40-OX40L signaling as a potential therapeutic target in the treatment of allergic airway inflammation. PMID:25839234

  9. Factor-dependent in vitro growth of human normal bone marrow-derived basophil-like cells

    PubMed Central

    1983-01-01

    A factor(s) present in supernatants from lectin-stimulated peripheral blood mononuclear cells promoted the production of basophil-like cells in liquid cultures of normal human bone marrow cells. The cultured basophil-like cells had lobulated or round nuclei, and the cytoplasmic granules stained metachromatically with toluidine blue and azurophilic with Giemsa. 20% of the metachromatically staining cells were peroxidase positive but not positive for nonspecific esterase. The histamine content was 0.5-2 pg/cell. The basophil-like cells released histamine upon challenge with calcium ionophore A23187 but not with compound 48/80. They also released histamine with anti-IgE when passively sensitized with human myeloma IgE. The development of basophil-like cells was promoted in a dose-dependent fashion by a factor(s) in the conditioned medium. Blocking of cell proliferation with hydroxyurea or X irradiation inhibited the development of basophil- like cells. The production of the factor was dependent on the presence of T cells. The factor was different from interleukin 2 and its molecular weight was estimated to be 25,000-40,000 by gel filtration on a Sephacryl S-200 column. Thus, human basophil-like cells derived from normal bone marrow cells can grow and differentiate in vitro under the regulation of T cells. PMID:6193237

  10. Depletion of acidic phosphopeptides by SAX to improve the coverage for the detection of basophilic kinase substrates.

    PubMed

    Dong, Mingming; Ye, Mingliang; Cheng, Kai; Song, Chunxia; Pan, Yanbo; Wang, Chunli; Bian, Yangyang; Zou, Hanfa

    2012-09-07

    The Ser/Thr protein kinases fall into three major subgroups, pro-directed, basophilic, and acidophilic, on the basis of the types of substrate sequences that they preferred. Despite many phosphoproteomics efforts that have been taken for global profiling of phosphopeptides, methodologies focusing on analyzing a particular type of kinase substrates have seldom been reported. Selective enrichment of phosphopeptides from basophilic kinase substrates is difficult because basophilic motifs are cleaved by trypsin during digestion. In this study, we develop a negative enrichment strategy to enhance the identification of basophilic kinase substrates. This method is based on an observation that high pH strong anion exchange (SAX) chromatography can separate tryptic phosphopeptides according to the number of acidic amino acidic residues that they have. Thus, SAX was applied to deplete acidic phosphopeptides from the phosphopeptide mixture, which improved the coverage for the detection of basophilic kinase substrates. The SAX depletion approach was further combined with online SCX-RP separation for large-scale analysis of mouse liver phosphoproteome, which resulted in the identification of 6944 phosphorylated sites. It was found that motifs associated with basophilic kinases prevail for these identified phosphorylated sites.

  11. Epidermal keratinocyte-derived basophil promoting activity. Role of interleukin 3 and soluble CD23.

    PubMed Central

    Dalloul, A H; Arock, M; Fourcade, C; Béranger, J Y; Jaffray, P; Debré, P; Mossalayi, M D

    1992-01-01

    Human epidermal keratinocytes (EK) secrete factors able to sustain the proliferation of early myeloid cells and, in particular, the generation of basophils. This activity was previously attributed to IL-3, although no definitive in situ demonstration of this cytokine was provided. In regard to the possible physiological relevance of these data, we investigated herein the nature of EK-derived factors responsible for basophil promotion. Our data show that EK-derived supernatants (EK-sup) contain IL-3 as well as soluble CD23 (sCD23), both known for their colony stimulating activity. Messenger RNA for IL-3 and CD23 were also detected in EK. Blocking experiments using specific neutralizing monoclonal antibodies (mAb) further indicate that EK-derived basophil promoting activity is mainly due to the presence of IL-3 and sCD23 in EK-sup. Furthermore, by contrast to IL-3, sCD23 secretion by EK is cortisone sensitive and highly enhanced by IL-4, suggesting distinct regulatory mechanisms for their production. Images PMID:1401061

  12. Supportive Care for Chronic Lymphocytic Leukemia

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Supportive Care for Chronic Lymphocytic Leukemia Supportive care for chronic lymphocytic leukemia (CLL) is ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  13. Basophil activation test for investigation of IgE-mediated mechanisms in drug hypersensitivity.

    PubMed

    Steiner, Markus; Harrer, Andrea; Lang, Roland; Schneider, Michael; Ferreira, Tima; Hawranek, Thomas; Himly, Martin

    2011-09-16

    Hypersensitivity reactions against non-steroidal anti-inflammatory drugs (NSAIDs) like propyphenazone (PP) and diclofenac (DF) can manifest as Type I-like allergic reactions (1). In clinical practice, diagnosis of drug hypersensitivity is mainly performed by patient history, as skin testing is not reliable and oral provocation testing bears life-threatening risks for the patient (2). Hence, evidence for an underlying IgE-mediated pathomechanism is hard to obtain. Here, we present an in vitro method based on the use of human basophils derived from drug-hypersensitive patients that mimics the allergic effector reaction in vivo. As basophils of drug-allergic patients carry IgE molecules specific for the culprit drug, they become activated upon IgE receptor crosslinking and release allergic effector molecules. The activation of basophils can be monitored by the determination of the upregulation of CD63 surface expression using flow cytometry (3). In the case of low molecular weight drugs, conjugates are designed to enable IgE receptor crosslinking on basophils. As depicted in Figure 1, two representatives of NSAIDs, PP and DF, are covalently bound to human serum albumin (HSA) via a carboxyl group reacting with the primary amino group of lysine residues. DF carries an intrinsic carboxyl group and, thus, can be used directly (4), whereas a carboxyl group-containing derivative of PP had to be organochemically synthesized prior to the study (1). The coupling degree of the low molecular weight compounds on the protein carrier molecule and their spatial distribution is important to guarantee crosslinking of two IgE receptor molecules. The here described protocol applies high performance-size exclusion chromatography (HPSEC) equipped with a sequential refractive index (RI) and ultra violet (UV) detection system for determination of the coupling degree. As the described methodology may be applied for other drugs, the basophil activation test (BAT) bears the potential to be

  14. Leukemia & Lymphoma Society

    MedlinePlus

    ... Light The Night Man & Woman of the Year Leukemia Cup Regatta Student Series Lifestyle Community Careers at ... Special Projects Beat AML Patients & caregivers Disease Information Leukemia Lymphoma Myeloma Myelodysplastic Syndromes Myeloproliferative Neoplasms Childhood Blood ...

  15. Acute Myeloid Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  16. Acute Lymphocytic Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, however, the bone marrow produces abnormal white blood ...

  17. Chronic Myeloid Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  18. Chronic Lymphocytic Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  19. Acute Lymphocytic Leukemia

    MedlinePlus

    ... treatment of acute lymphoblastic leukemia in children. In: Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa.: ... et al. Acute lymphoblastic leukemia in adults. In: Hematology: Basic Principles and Practice. 6th ed. Philadelphia, Pa.: ...

  20. Exposure to food allergens through inflamed skin promotes intestinal food allergy through the thymic stromal lymphopoietin-basophil axis.

    PubMed

    Noti, Mario; Kim, Brian S; Siracusa, Mark C; Rak, Gregory D; Kubo, Masato; Moghaddam, Amin E; Sattentau, Quentin A; Comeau, Michael R; Spergel, Jonathan M; Artis, David

    2014-05-01

    Exposure to food allergens through a disrupted skin barrier has been recognized as a potential factor in the increasing prevalence of food allergy. We sought to test the immunologic mechanisms by which epicutaneous sensitization to food allergens predisposes to intestinal food allergy. Mice were epicutaneously sensitized with ovalbumin or peanut on an atopic dermatitis-like skin lesion, followed by intragastric antigen challenge. Antigen-specific serum IgE levels and T(H)2 cytokine responses were measured by ELISA. Expression of type 2 cytokines and mast cell proteases in the intestine were measured by using real-time PCR. Accumulation of basophils in the skin and mast cells in the intestine was examined by using flow cytometry. In vivo basophil depletion was achieved by using diphtheria toxin treatment of Baso-DTR mice. For cell-transfer studies, the basophil population was expanded in vivo by means of hydrodynamic tail vein injection of thymic stromal lymphopoietin (TSLP) cDNA plasmid. Sensitization to food allergens through an atopic dermatitis-like skin lesion is associated with an expansion of TSLP-elicited basophils in the skin that promote antigen-specific T(H)2 cytokine responses, increased antigen-specific serum IgE levels, and accumulation of mast cells in the intestine, promoting the development of intestinal food allergy. Critically, disruption of TSLP responses or depletion of basophils reduced the susceptibility to intestinal food allergy, whereas transfer of TSLP-elicited basophils into intact skin promoted disease. Epicutaneous sensitization on a disrupted skin barrier is associated with accumulation of TSLP-elicited basophils, which are necessary and sufficient to promote antigen-induced intestinal food allergy. Copyright © 2014 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  1. The novel endogenous cannabinoid 2-arachidonoylglycerol is inactivated by neuronal- and basophil-like cells: connections with anandamide.

    PubMed Central

    Di Marzo, V; Bisogno, T; Sugiura, T; Melck, D; De Petrocellis, L

    1998-01-01

    The novel endogenous cannabinoid 2-arachidonoylglycerol (2-AG) was rapidly inactivated by intact rat basophilic leukaemia (RBL-2H3) and mouse neuroblastoma (N18TG2) cells through diffusion/hydrolysis/reacylation processes. The hydrolysis of 2-AG was inhibited by typical esterase inhibitors and by more specific blockers of 'fatty acid amide hydrolase' (FAAH), the enzyme catalysing the hydrolysis of the other 'endocannabinoid', anandamide (AEA). No evidence for a facilitated-diffusion process was found. A 2-AG-hydrolysing activity was detected in homogenates from both cell lines, with the highest levels in membrane fractions. It exhibited an optimal pH at 10, and recognized both 2- and 1(3)- isomers of monoarachidonoylglycerol with similar efficiencies. The apparent Km and Vmax values for -3H-2-AG hydrolysis were 91 microM and 29 microM and 2.4 and 1.8 nmol.min-1.mg of protein-1 respectively in N18TG2 and RBL-2H3 cells. [3H]2-AG hydrolysis was inhibited by Cu2+, Zn2+ and p-hydroxymercuribenzoate, and by 2- or 1(3)-monolinoleoyl- and -linolenoyl-glycerols, but not by the oleoyl, palmitoyl and myristoyl congeners. Purified fractions from solubilized membrane proteins catalysed, at pH 9.5, the hydrolysis of 2-AG as well as AEA. Accordingly, AEA as well as FAAH inhibitors, including arachidonoyltrifluoromethyl ketone (ATFMK), blocked [3H]2-AG hydrolysis by N18TG2 and RBL-2H3 membranes, whereas 2-AG inhibited [14C]AEA hydrolysis. FAAH blockade by ATFMK preserved from inactivation the 2-AG synthesized de novo by intact N18TG2 cells stimulated with ionomycin. These data suggest that FAAH may be one of the enzymes deputed to the physiological inactivation of 2-AG, and create intriguing possibilities for the cross-regulation of 2-AG and AEA levels. PMID:9512456

  2. Low dose assessment of the carcinogenicity of furan in male F344/N Nctr rats in a 2-year gavage study.

    PubMed

    Von Tungeln, Linda S; Walker, Nigel J; Olson, Greg R; Mendoza, Maria C B; Felton, Robert P; Thorn, Brett T; Marques, M Matilde; Pogribny, Igor P; Doerge, Daniel R; Beland, Frederick A

    2017-01-01

    Furan is a volatile organic chemical that is a contaminant in many common foods. Furan is hepatocarcinogenic in mice and rats; however, the risk to humans from dietary exposure to furan cannot be estimated accurately because the lowest tested dose of furan in a 2-year bioassay in rats gave nearly a 100% incidence of cholangiocarcinoma. To provide bioassay data that can be used in preparing risk assessments, the carcinogenicity of furan was determined in male F344/N Nctr rats administered 0, 0.02, 0.044, 0.092, 0.2, 0.44, 0.92, and 2 mg furan/kg body weight (BW) by gavage 5 days/week for 2 years. Exposure to furan was associated with the development of malignant mesothelioma on membranes surrounding the epididymis and on the testicular tunics, with the increase being significant at 2 mg furan/kg BW. There was also a dose-related increase in the incidence of mononuclear cell leukemia, with the increase in incidence being significant at 0.092, 0.2, 0.92, and 2 mg furan/kg BW. Dose-related non-neoplastic liver lesions included cholangiofibrosis, mixed cell foci, basophilic foci, biliary tract hyperplasia, oval cell hyperplasia, regenerative hyperplasia, and cytoplasmic vacuolization. The most sensitive non-neoplastic lesion was cholangiofibrosis, the frequency of which increased significantly at 0.2 mg furan/kg BW. Published by Elsevier Ltd.

  3. The antinociception of oxytocin on colonic hypersensitivity in rats was mediated by inhibition of mast cell degranulation via Ca2+-NOS pathway

    PubMed Central

    Gong, Liping; Li, Jing; Tang, Yan; Han, Ting; Wei, Chuanfei; Yu, Xiao; Li, Jingxin; Wang, Rong; Ma, Xuelian; Liu, Kejing; Geng, Lingyun; Liu, Shaozhuang; Yan, Bing; Liu, Chuanyong

    2016-01-01

    This study was conducted to investigate the effects of oxytocin (OT) on visceral hypersensitivity/pain and mast cell degranulation and the underlying mechanisms. We found that oxytocin receptor (OTR) was expressed in colonic mast cells in humans and rats, as well as in human mast cell line-1 (HMC-1), rat basophilic leukemia cell line (RBL-2H3) and mouse mastocytoma cell line (P815). OT decreased 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced visceral hypersensitivity, colonic mast cell degranulation and histamine release after mast cell degranulation in rats. Also, OT attenuated the compound 48/80 (C48/80)-evoked histamine release in P815 cells and inward currents, responsible for the mast cell degranulation, in HMC-1, RBL-2H3 and P815 cells. Moreover, these protective effects of OT against visceral hypersensitivity and mast cell degranulation were eliminated by coadministration of OTR antagonist atosiban or a nonselective inhibitor of nitric oxide synthase (NOS), NG-Methyl-L-arginine acetate salt (L-NMMA). Notably, OT evoked a concentration-dependent increase of intracellular Ca2+ in HMC-1, RBL-2H3 and P815 cells, which was responsible for the activation of neuronal NOS (NOS1) and endothelial NOS (NOS3). Our findings strongly suggest that OT might exert the antinociception on colonic hypersensitivity through inhibition of mast cell degranulation via Ca2+-NOS pathway. PMID:27538454

  4. Mechanism of activation of human basophils by Staphylococcus aureus Cowan 1.

    PubMed Central

    Marone, G; Tamburini, M; Giudizi, M G; Biagiotti, R; Almerigogna, F; Romagnani, S

    1987-01-01

    We investigated the capacity of Staphylococcus aureus Cowan 1 and S. aureus Wood 46 to induce histamine release from human basophils in vitro. S. aureus Cowan 1 (10(5) to 10(7)/ml), which synthesizes protein A (Staph A), stimulated the release of histamine from basophils, whereas S. aureus Wood 46 (10(5) to 2 X 10(7)/ml), which does not synthesize Staph A, did not induce histamine secretion. Soluble Staph A (10(-3) to 10 micrograms/ml), but not staphylococcal enterotoxin A, induced histamine secretion from human basophils. Staph A binds through its classical site to the Fc region of human immunoglobulin G (IgG) and through its alternative site to the Fab portion of the different human immunoglobulins. Hyperiodination of Staph A, which destroys over 90% of the original Fc reactivity without altering the Fab-binding site, did not alter the ability of the protein to induce histamine release. The stimulating effect of Staph A was dose dependently inhibited by preincubation with human polyclonal IgG (0.3 to 100 micrograms/ml) and a human monoclonal IgM (0.3 to 100 micrograms/ml) which have F(ab')-Staph A reactivity. In contrast, rabbit IgG, which possesses only Fc-Staph A reactivity, and a Staph A-unreactive human monoclonal IgM did not inhibit Staph A activity. Similar results were obtained with intact S. aureus Cowan 1. Preincubation with either Staph A or anti-IgE (rabbit anti-Fc epsilon) resulted in complete desensitization to a subsequent challenge with the homologous stimulus. Staph A and anti-IgE induced partial cross-densensitization to the heterologous stimulus. Cells preincubated with anti-IgG (rabbit anti-Fc gamma) lost a small but significant part of their ability to release with Staph A but did not lose their response to anti-IgE. Basophils from which IgE had been dissociated by brief exposure to lactic acid no longer released histamine in response to anti-IgE and Staph A. When basophils from which IgE had been dissociated were incubated with human

  5. Mast cells and basophils are essential for allergies: mechanisms of allergic inflammation and a proposed procedure for diagnosis.

    PubMed

    He, Shao-Heng; Zhang, Hui-Yun; Zeng, Xiao-Ning; Chen, Dong; Yang, Ping-Chang

    2013-10-01

    The current definition of allergy is a group of IgE-mediated diseases. However, a large portion of patients with clinical manifestations of allergies do not exhibit elevated serum levels of IgE (sIgEs). In this article, three key factors, ie soluble allergens, sIgEs and mast cells or basophils, representing the causative factors, messengers and primary effector cells in allergic inflammation, respectively, were discussed. Based on current knowledge on allergic diseases, we propose that allergic diseases are a group of diseases mediated through activated mast cells and/or basophils in sensitive individuals, and allergic diseases include four subgroups: (1) IgE dependent; (2) other immunoglobulin dependent; (3) non-immunoglobulin mediated; (4) mixture of the first three subgroups. According to our proposed definition, pseudo-allergic-reactions, in which mast cell or basophil activation is not mediated via IgE, or to a lesser extent via IgG or IgM, should be non-IgE-mediated allergic diseases. Specific allergen challenge tests (SACTs) are gold standard tests for diagnosing allergies in vivo, but risky. The identification of surface membrane activation markers of mast cells and basophils (CD203c, CCR3, CD63, etc) has led to development of the basophil activation test (BAT), an in vitro specific allergen challenge test (SACT). Based on currently available laboratory allergy tests, we here propose a laboratory examination procedure for allergy.

  6. Mast cells and basophils in inflammatory and tumor angiogenesis and lymphangiogenesis.

    PubMed

    Marone, Gianni; Varricchi, Gilda; Loffredo, Stefania; Granata, Francescopaolo

    2016-05-05

    Angiogenesis, namely, the growth of new blood vessels from pre-existing ones, is an essential process of embryonic development and post-natal growth. In adult life, it may occur in physiological conditions (menstrual cycle and wound healing), during inflammatory disorders (autoimmune diseases and allergic disorders) and in tumor growth. The angiogenic process requires a tightly regulated interaction among different cell types (e.g. endothelial cells and pericytes), the extracellular matrix, several specific growth factors (e.g. VEGFs, Angiopoietins), cytokines and chemokines. Lymphangiogenesis, namely, the growth of new lymphatic vessels, is an important process in tumor development, in the formation of metastasis and in several inflammatory and metabolic disorders. In addition to tumors, several effector cells of inflammation (mast cells, macrophages, basophils, eosinophils, neutrophils, etc.) are important sources of a wide spectrum of angiogenic and lymphangiogenic factors. Human mast cells produce a large array of angiogenic and lymphangiogenic molecules. Primary human mast cells and two mast cell lines constitutively express several isoforms of angiogenic (VEGF-A and VEGF-B) and the two lymphangiogenic factors (VEGF-C and VEGF-D). In addition, human mast cells express the VEGF receptor 1 (VEGFR-1) and 2 (VEGFR-2), the co-receptors neuropilin-1 (NRP1) and -2 (NRP2) and the Tie1 and Tie2 receptors. Immunologically activated human basophils selectively produce VEGF-A and -B, but not VEGF-C and -D. They also release Angiopoietin1 that activates Tie2 on human mast cells. Collectively, these findings indicate that human mast cells and basophils might participate in the complex network involving inflammatory and tumor angiogenesis and lymphangiogenesis.

  7. Individual strains of Lactobacillus paracasei differentially inhibit human basophil and mouse mast cell activation

    PubMed Central

    Cassard, Lydie; Lalanne, Ana Inés; Garault, Peggy; Cotillard, Aurélie; Chervaux, Christian; Wels, Michiel; Smokvina, Tamara

    2016-01-01

    Abstract Introduction The microbiota controls a variety of biological functions, including immunity, and alterations of the microbiota in early life are associated with a higher risk of developing allergies later in life. Several probiotic bacteria, and particularly lactic acid bacteria, were described to reduce both the induction of allergic responses and allergic manifestations. Although specific probiotic strains were used in these studies, their protective effects on allergic responses also might be common for all lactobacilli. Methods To determine whether allergic effector cells inhibition is a common feature of lactobacilli or whether it varies among lactobacilli strains, we compared the ability of 40 strains of the same Lactobacillus paracasei species to inhibit IgE‐dependent mouse mast cell and human basophil activation. Results We uncovered a marked heterogeneity in the inhibitory properties of the 40 Lactobacillus strains tested. These segregated into three to four clusters depending on the intensity of inhibition. Some strains inhibited both mouse mast cell and human basophil activation, others strains inhibited only one cell type and another group induced no inhibition of activation for either cell type. Conclusions Individual Lactobacillus strains of the same species differentially inhibit IgE‐dependent activation of mouse mast cells and human basophils, two cell types that are critical in the onset of allergic manifestations. Although we failed to identify specific bacterial genes associated with inhibition by gene‐trait matching analysis, our findings demonstrate the complexity of the interactions between the microbiota and the host. These results suggest that some L. paracasei strains might be more beneficial in allergies than others strains and provide the bases for a rational screening of lactic acid bacteria strains as next‐generation probiotics in the field of allergy. PMID:27621812

  8. Evidence of pathway-specific basophil anergy induced by peanut oral immunotherapy in peanut-allergic children.

    PubMed

    Thyagarajan, A; Jones, S M; Calatroni, A; Pons, L; Kulis, M; Woo, C S; Kamalakannan, M; Vickery, B P; Scurlock, A M; Wesley Burks, A; Shreffler, W G

    2012-08-01

    In Westernized countries, over 1% of the population is allergic to peanuts or tree nuts, which carries a risk of severe allergic reactions. Several studies support the efficacy of peanut oral immunotherapy (OIT) for reducing the clinical sensitivity of affected individuals; however, the mechanisms of this effect are still being characterized. One mechanism that may contribute is the suppression of effector cells, such as basophils. Basophil anergy has been characterized in vitro as a pathway-specific hyporesponsiveness; however, this has not been demonstrated to occur in vivo. To evaluate the hypothesis that basophil anergy occurs in vivo due to chronic allergen exposure in the setting of a clinical oral immunotherapy trial. Samples of peripheral blood were obtained from subjects during a placebo-controlled clinical trial of peanut OIT. Basophil reactivity to in vitro stimulation with peanut allergen and controls was assessed by the upregulation of activation markers, CD63 and CD203c, measured by flow cytometry. The upregulation of CD63 following stimulation of the IgE receptor, either specifically with peanut allergen or non-specifically with anti-IgE antibody, was strongly suppressed by active OIT. However, OIT did not significantly suppress this response in basophils stimulated by the distinct fMLP receptor pathway. In the subset of subjects with egg sensitization, active peanut OIT also suppressed CD63 upregulation in response to stimulation with egg allergen. Allergen OIT also suppressed the upregulation of CD203c including in response to stimulation with IL-3 alone. Peanut OIT induces a hyporesponsive state in basophils that is consistent with pathway-specific anergy previously described in vitro. This suggests the hypothesis that effector cell anergy could contribute to clinical desensitization. © 2012 Blackwell Publishing Ltd.

  9. Differential modulation of IgE-dependent activation of human basophils by ambroxol and related secretolytic analogues.

    PubMed

    Gibbs, B F

    2009-01-01

    Ambroxol is a widely used secretolytic agent originally developed from vasicine, a natural alkaloid found in Adhatoda vasica, extracts of which have been used to treat bronchitis, asthma, and rheumatism. We previously reported that ambroxol inhibits IgE-dependent mediator secretion from human mast cells and basophils, key effector cells of allergic inflammation. Here, the mechanisms involved in the inhibitory properties of ambroxol were assessed in comparison to other secretolytic analogues (e.g. vasicine, bromhexine, sputolysin). The results show that, in comparison to ambroxol, which reduced IgE-dependent histamine release from basophils at 10 microM-1 mM, the release of the amine was only moderately reduced by sputolysin and vasicine at 1 mM. In contrast, above 10 microM, bromhexine was found to be toxic to basophils in vitro as evidenced by induction of histamine release and reduced cell viability. In contrast, the inhibitory actions of ambroxol at concentrations below 1 mM were not toxic and entirely reversible. Ambroxol was also more potent than either sputolysin or vasicine in attenuating basophil IL-4 and IL-13 secretions, whereas bromhexine-induced suppression of de novo cytokine synthesis was due to toxic effects. Additionally, ambroxol reduced IgE-dependent p38 MAPK phosphorylation in basophils, unlike bromhexine, sputolysin and vasicine. These results clearly show that ambroxol is both more potent and effective at inhibiting IgE-dependent basophil mediator release and p38 MAPK activity than the other secretolytic analogues employed. The therapeutic potential of ambroxol as an anti-allergic agent is further underlined by these data.

  10. Preliminary characterization of diacylglycerol generation in human basophils: temporal relationship to histamine release and resolution of degranulation.

    PubMed

    Oriente, A; Hundley, T; Hubbard, W C; MacGlashan, D W

    1997-05-01

    Purified human basophils were examined for changes in diacylglycerol levels to determine whether the transient nature of a N-formyl-methionyl-leucyl-phenylalanine (fMLP) -stimulated elevation in membrane protein kinase C (PKC) activity could be explained by the transient production of diacylglycerol (DAG). In preliminary experiments total DAG levels were measured by the DAG kinase assay. Although elevations followed stimulation with 1 microM fMLP (basal levels of 15 pmol/10(6) basophils vs. 45 pmol/10(6) basophils at the 3-min time point), there were no detectable changes in the first 60 s of the reaction. Histamine release is typically complete by 30-45 s. Measurement of inositol trisphosphate indicated a rapid increase by 5 s of 2.5 pmol/10(6) basophils. If DAG were produced at similar levels, the DAG kinase assay would not have detected the elevation. Consequently, fMLP-stimulated basophils were examined for changes in 1-stearoyl, 2-arachidonoyl, 3-sn-glycerol (SA-DAG) and 1-oleoyl, 2-arachidonoyl, 3-sn-glycerol by GC-NICIMS (negative ion chemical ionization mass spectroscopy). A 5-s elevation in these two species averaged 2 pmol/10(6) basophils, consistent with the inositol trisphosphate levels and occurring during the period of histamine release. However, a much more pronounced second phase to the SA-DAG response also occurred, mirroring the total DAG levels. This second phase of the DAG response, either total or SA-DAG, was transient on a time scale temporally coincident with the appearance and resolution of degranulation sacs as measured by fluorescence microscopy. These data suggest that there is selective generation of DAG species in the early reaction and the later appearance of DAG may be related to the formation and resolution of granule structures that follow the secretion of histamine.

  11. CTAB-coated gold nanorods elicit allergic response through degranulation and cell death in human basophils

    NASA Astrophysics Data System (ADS)

    Cheung, Ka Lun; Chen, Huanjun; Chen, Qiulan; Wang, Jianfang; Ho, Ho Pui; Wong, Chun Kwok; Kong, Siu Kai

    2012-07-01

    The effect of CTAB (cetyltrimethylammonium bromide)- or PEG (polyethylene glycol)-coated gold-nanorods (Au-NRs) on the non-IgE mediated allergic response was studied. We found that the CTAB-Au-NRs released more allergic mediators such as histamine and β-hexosaminidase from human basophil KU812, a common model for studying allergy, after 20 min incubation. Also, the CTAB-Au-NRs induced more apoptosis than the PEG-Au-NRs in KU812 24 h after treatment. These short- and long-term effects were not solely due to the CTAB residues in the supernatant desorbed from the Au-NRs.The effect of CTAB (cetyltrimethylammonium bromide)- or PEG (polyethylene glycol)-coated gold-nanorods (Au-NRs) on the non-IgE mediated allergic response was studied. We found that the CTAB-Au-NRs released more allergic mediators such as histamine and β-hexosaminidase from human basophil KU812, a common model for studying allergy, after 20 min incubation. Also, the CTAB-Au-NRs induced more apoptosis than the PEG-Au-NRs in KU812 24 h after treatment. These short- and long-term effects were not solely due to the CTAB residues in the supernatant desorbed from the Au-NRs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c2nr30435j

  12. [Basophilic line of the articular cartilage in normal and various pathological states].

    PubMed

    Gongadze, L R

    1987-04-01

    Epiphyses of long tubular bones in the man and animals of various age, as well as experimental material of the adjuvant arthritis, with special reference to the basal part of the articular cartilage have been studied by means of histological, histochemical and histometrical methods. The structural-chemical organization of the basophilic line (tidemark) of the articular cartilage ensures its barrier role and participation in regulating selective permeability. Reconstruction of the tidemark in the process of physiological ageing and in cases of the articular pathology is aimed to preserve its integrity and in this way a complete differentiation of the noncalcified and calcified structures is secured. Disturbance of the basophilic line results in changes of the articular selective permeability, in invasion of vessels and structural elements of the bone marrow, and in development of profound distrophic and destructive changes of the cartilage--in deforming artrosis. Deflations in the structural-chemical organization of the tidemark indicate certain disturbances in the state of the system articular cartilage--subchondral bone. These data can be of prognostic importance.

  13. Qualitative characteristics of histamine release from human basophils by covalently cross-linked LgE

    SciTech Connect

    Kagey-Sobotka, A.; Dembo, M.; Goldstein, B.; Metzger, H.; Lichtenstein, L.M.

    1981-12-01

    The effects of permanent oligomers of human lgE produced was studied using the cross-linking reagent, dimethyl suberimidate, on histamine release from human basophils. lgE dimers were found to be sufficient stimuli for both release and desensitization of these cells; monomeric lgE had no effect. Histamine release was augmented by deuterium oxide (D/sub 2/O) in the media, but D/sub 2/O was not an absolute requirement to observe release. Desensitization by the dimeric lgE was specific in that the response to anti-lgE was not affected by preincubation of the leukocytes with the lgE dimer under suboptimal releasing conditions. lgE trimers and higher oligomers of lgE also caused both release and desensitization. lgE also trimers were 3- to 4-fold more effective than lgE dimers with regard to the amount required for 50% histamine release. Dilution studies with monomeric lgE suggested that the difference was due to the presence of more ''active'' dimers in the trimeric lgE fractions. We conclude that dimeric lgE, by juxtaposing 2 receptors on the basophil membrane, is the ''unit signal'' for both release and desensitization of these cells.

  14. [Basophil degranulation test (BDT) as a parameter of hyposensitization with Hymenoptera venoms].

    PubMed

    Dietschi, R; Wüthrich, B; Marti-Wyss, S; Cuhat, J

    1987-10-31

    In a population of 24 insect sting allergy patients undergoing venom immunotherapy the basophil degranulation test (BDT) in the patient sera ("unwashed" BDT) and with washed leukocytes ("washed" BDT) after incubation with bee and wasp (yellow jacket) venom was performed before and during treatment. Venom specific IgE and IgG antibodies, detected by means of RAST, were also monitored. The "unwashed" BDT usually became negative within 6-9 months of beginning immunotherapy, whereas the IgE-RAST was still clearly positive. This was attributed to the blocking influence of the venom specific IgG antibodies induced by the venom therapy. In fact, at this time the BDT with "washed" blood leukocytes, i.e. after elimination of the serum antibodies, was generally still positive. Only during further immunotherapy did cellular sensitization in the "washed" BDT gradually disappear, whereas the IgE-RAST usually turned out weakly positive. A third of the patients showed simultaneously negative results of "unwashed" and "washed" BDT, independently of venom specific IgE and IgG levels. These findings suggest a specific reactivity change of the blood basophils (cellular desensitization) induced by the immunotherapy. The BDT can be used as an immunological parameter for IgG-monitoring of the course of venom immunotherapy and--in addition to skin tests and IgE-RAST--as a further criterion for deciding to stop venom therapy if it turns negative with the washed cells.

  15. What You Need to Know about Leukemia

    MedlinePlus

    ... Publications Reports What You Need To Know About™ Leukemia This booklet is about leukemia. Leukemia is cancer of the blood and bone marrow ( ... This book covers: Basics about blood cells and leukemia Types of doctors who treat leukemia Treatments for ...

  16. Targeted Therapy for Acute Lymphocytic Leukemia

    MedlinePlus

    ... Adults Treating Acute Lymphocytic Leukemia Targeted Therapy for Acute Lymphocytic Leukemia In recent years, new drugs that target specific ... Typical Treatment of Acute Lymphocytic Leukemia More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  17. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePlus

    ... Adults About Acute Lymphocytic Leukemia (ALL) What Is Acute Lymphocytic Leukemia? Cancer starts when cells in the body begin ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  18. Flavopiridol, Cytarabine, and Mitoxantrone in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2013-10-07

    Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. [Hairy cell leukemia].

    PubMed

    Dietrich, S; Andrulis, M; Zenz, T

    2015-04-01

    Hairy cell leukemia was initially described as a distinct entity in 1958. It is rare B-cell malignancy characterized by an indolent course. Advances in the treatment and understanding of the biology of hairy cell leukemia have made the disease exquisitely amenable to treatment. This review summarizes the present understanding of hairy cell leukemia with a particular focus on the development of novel and targeted approaches to treatment.

  20. Gliadin does not induce mucosal inflammation or basophil activation in patients with nonceliac gluten sensitivity.

    PubMed

    Bucci, Cristina; Zingone, Fabiana; Russo, Ilaria; Morra, Ivonne; Tortora, Raffaella; Pogna, Norberto; Scalia, Giulia; Iovino, Paola; Ciacci, Carolina

    2013-10-01

    Nonceliac gluten-sensitive (NCGS) patients report intestinal and extra-intestinal symptoms shortly after ingesting gluten; these symptoms disappear on gluten-free diets, although these patients have no serologic markers of celiac disease or intestinal damage. In fact, there is no evidence for mucosal or serologic modifications in those individuals. We investigated immunologic responses of duodenal mucosa samples and peripheral blood basophils, isolated from NCGS patients, after exposure to gliadin. Participants underwent a complete clinical evaluation to exclude celiac disease while on a gluten-containing diet, a skin prick test to exclude wheat allergy, and upper endoscopy (n = 119) at 2 tertiary medical centers in Italy. Patients were considered to have NCGS based on their symptoms and the current definition of the disorder. Subjects were assigned to the following groups: patients with celiac disease on gluten-free diets (n = 34), untreated patients with celiac disease (n = 35), patients with NCGS (n = 16), or controls (n = 34). Duodenal biopsy samples collected during endoscopy were incubated with gliadin peptides, and levels of inflammatory markers were assessed. Peripheral blood basophils were extracted and incubated with gliadin peptides or a mix of wheat proteins; activation was assessed based on levels of CD203c, CD63, and CD45. Duodenal mucosa samples collected from 69 patients with celiac disease showed markers of inflammation after incubation with gliadin. Some, but not all, markers of inflammation were detected weakly in biopsy samples from 3 controls and 3 NCGS patients (P = .00 for all markers). There were no significant increases in the levels of CD63 and CD203c in NCGS patients. Unlike the duodenal mucosa from patients with celiac disease, upon incubation with gliadin, mucosa from patients with NCGS does not express markers of inflammation, and their basophils are not activated by gliadin. The in vitro gliadin challenge therefore should not

  1. Ibrutinib, a BTK inhibitor used for treatment of lymphoproliferative disorders, eliminates both aeroallergen skin test and basophil activation test reactivity.

    PubMed

    Regan, Jennifer A; Cao, Yun; Dispenza, Melanie C; Ma, Shuo; Gordon, Leo I; Petrich, Adam M; Bochner, Bruce S

    2017-04-04

    Ibrutinib, a Bruton's tyrosine kinase (BTK) inhibitor, was shown to eliminate skin test reactivity in vivo and IgE-dependent basophil activation testing ex vivo. Blockade of the BTK pathway may represent a novel therapeutic strategy for the effective reduction of allergic reactivity.

  2. STUDIES IN THE BLOOD CYTOLOGY OF THE RABBIT : IV. CONSECUTIVE NEUTROPHILE, BASOPHILE, AND EOSINOPHILE OBSERVATIONS ON GROUPS OF NORMAL RABBITS.

    PubMed

    Pearce, L; Casey, A E

    1930-07-31

    Consecutive weekly observations on the neutrophile, the basophile, and the eosinophile counts of the peripheral blood were made on 5 groups of normal rabbits, a total of 45 animals, during a period of 20 months from October, 1927 to July, 1929. Individual groups were examined 8 to 35 weeks. In the case of the 4 groups followed 13 to 35 weeks, the general trend of the neutrophile cells was towards increased mean values; with the group followed 8 weeks, decreasing values were found. An increase in the mean values of the basophile cells was observed in the two groups of rabbits followed in 1927-28; in the groups of 1928-29, the mean values decreased. The mean values of the eosinophile cells showed no definite trends but the findings were characterized by abrupt and marked fluctuations. The periods of greatest irregularity in mean neutrophile and eosinophile values occurred in the fall and the late winter and spring months of both years, but in the case of the basophiles, the irregularities were distributed throughout the first year and occurred chiefly in the winter months of the second year. The major trends and many of the minor fluctuations as well which were observed in the mean cell values of one group of rabbits were also generally seen in another group examined during the same months. The general levels of the neutrophile, the basophile, and the eosinophile mean values in the groups examined during 1927-28 were higher than in the groups of 1928-29.

  3. iNKT Cells Are Responsible for the Apoptotic Reduction of Basophils That Mediate Th2 Immune Responses Elicited by Papain in Mice Following γPGA Stimulation

    PubMed Central

    Park, Se-Ho; Hong, Seokmann

    2016-01-01

    Recent studies have demonstrated that Bacillus subtilis-derived poly-gamma glutamic acid (γPGA) treatment suppresses the development of allergic diseases such as atopic dermatitis (AD). Although basophils, an innate immune cell, are known to play critical roles in allergic immune responses and repeated long-term administration of γPGA results in decreased splenic basophils in an AD murine model, the underlying mechanisms by which γPGA regulates basophil frequency remain unclear. To investigate how γPGA modulates basophils, we employed basophil-mediated Th2 induction in vivo model elicited by the allergen papain protease. Repeated injection of γPGA reduced the abundance of basophils and their production of IL4 in mice, consistent with our previous study using NC/Nga AD model mice. The depletion of basophils by a single injection of γPGA was dependent on the TLR4/DC/IL12 axis. CD1d-dependent Vα14 TCR invariant natural killer T (iNKT) cells are known to regulate a variety of immune responses, such as allergy. Because iNKT cell activation is highly sensitive to IL12 produced by DCs, we evaluated whether the effect of γPGA on basophils is mediated by iNKT cell activation. We found that in vivo γPGA treatment did not induce the reduction of basophils in iNKT cell-deficient CD1d KO mice, suggesting the critical role of iNKT cells in γPGA-mediated basophil depletion at the early time points. Furthermore, increased apoptotic basophil reduction triggered by iNKT cells upon γPGA stimulation was mainly attributed to Th1 cytokines such as IFNγ and TNFα, consequently resulting in inhibition of papain-induced Th2 differentiation via diminishing basophil-derived IL4. Taken together, our results clearly demonstrate that γPGA-induced iNKT cell polarization toward the Th1 phenotype induces apoptotic basophil depletion, leading to the suppression of Th2 immune responses. Thus, elucidation of the crosstalk between innate immune cells will contribute to the design and

  4. Selective hypersensitivity to cefazolin and contribution of the basophil activation test.

    PubMed

    Almeida, J P; Lopes, A; Campos Melo, A; Pereira Santos, M C; Pereira Barbosa, M

    2017-03-01

    The authors present 2 case reports of selective cefazolin hypersensitivity: a 49 year-old woman with a history of two perioperative reactions (urticaria and severe anaphylaxis) after the use of rocuronium, propophol and cefazolin; a 36 year-old pregnant woman who developed facial erythema, lips angioedema and hypotension immediately after administration of ropivacain, sufentanil, cefazolin, oxytocin and ephedrine. In both cases, intradermal skin tests were positive for cefazolin. A basophil activation test was performed for cefazolin, which was positive in one patient. Oral challenge tests with penicillin, amoxicillin and other cephalosporins were negative. This selective hypersensitivity to cefazolin may be associated with a R1-side chain different from other beta-lactams.

  5. The basophil activation test: a sensitive test in the diagnosis of allergic immediate hypersensitivity to pristinamycin.

    PubMed

    Viel, Sébastien; Garnier, Lorna; Joly, Elodie; Rouzaire, Paul; Nosbaum, Audrey; Pralong, Pauline; Faudel, Amélie; Rioufol, Catherine; Bienvenu, Françoise; Bienvenu, Jacques; Berard, Frédéric

    2015-01-01

    Immediate hypersensitivity (IHS) reactions to macrolides and to macrolide-derived antibiotics like pristinamycin are uncommon. In this context, there is little data available to appreciate the true value of biological tools regarding the diagnosis of immediate allergy to pristinamycin. Here we assess the clinical usefulness of the basophil activation test (BAT) to differentiate allergic from nonallergic IHS to pristinamycin. Thirty-six patients were tested with skin tests as the gold standard and BAT. The BAT achieved a sensitivity of 76% and a specificity of 100%, implying an absence of false positive results. Multicenter studies remain to be performed to better define the sensitivity, specificity and interlaboratory variation of BAT in the diagnosis of allergy to pristinamycin and macrolides. © 2015 S. Karger AG, Basel.

  6. Cyclic AMP agonist inhibition increases at low levels of histamine release from human basophils

    SciTech Connect

    Tung, R.S.; Lichtenstein, L.M.

    1981-09-01

    The relationship between the intensity of the signal for antigen-induced immunoglobulin E-mediated histamine release from human basophils and the concentration of agonist needed to inhibit release has been determined. The agonists, prostaglandin E1, dimaprit, fenoterol, isobutylmethylxanthine and dibutyryl cyclic AMP, all act by increasing the cyclic AMP level. Each agonist was 10- to 1000-fold more potent (relative ID50) at low levels of histamine release (5-10% of total histamine) than at high levels (50-80%). Thus, the inhibitory potential of a drug is a function of the concentration of antigen used to initiate the response. Our results are now more in accord with the inhibitory profile of these drugs in human lung tissue. It is suggested that in vivo release is likely to be low and that this is the level at which to evaluate drugs in vitro.

  7. Relation of perceived nasal and bronchial hyperresponsiveness to FEV1, basophil counts, and methacholine response.

    PubMed Central

    Kauffmann, F; Neukirch, F; Annesi, I; Korobaeff, M; Doré, M F; Lellouch, J

    1988-01-01

    Perceived nasal and bronchial hyperresponsiveness to tobacco smoke and cold air were assessed in 912 working men in the Paris area. Baseline lung function measurements and peripheral leucocyte counts with standard differential counts were performed. At least one perceived nasal or bronchial hyperresponsiveness symptom was reported by 15.7%. Current smoking was significantly less frequent among those with cough induced by tobacco smoke. Rhinitis induced by cold air was associated with lower FEV1 (p less than 0.01) and the association remained after adjustment for smoking, asthma, and wheezing (p = 0.06). Symptoms induced by cold air were related to circulating basophils. Neither perceived nasal nor perceived bronchial hyperresponsiveness was significantly related to the airway response to methacholine in a sample of the group (n = 324) surveyed again five years later. The result suggest that the symptom of rhinitis provoked by cold air is a possible "new" risk factor or marker for chronic airflow limitation. PMID:3420556

  8. Cutaneous basophil responses and immune resistance of guinea pigs to ticks: passive transfer with peritoneal exudate cells or serum.

    PubMed

    Brown, S J; Askenase, P W

    1981-11-01

    Resistance to infestation by larval Amblyomma americanum or Rhipicephalus sanguineus ticks was transferred to naive guinea pigs with peritoneal exudate cells (PEC) or serum from donors immunized by prior infestation with homologous tick larvae. In the A. americanum system, PEC transfer induced 87% tick rejection, which was similar to the level of resistance in actively sensitized hosts. In the R. sanguineus system, PEC conferred resistance (39% rejection) that was weaker than in actively sensitized hosts (57% rejection). In both systems, immune serum conferred significant but weaker resistance (20 to 29% rejection). In actively sensitized hosts, resistance to each tick species was specific, but there was considerable cross-reactive resistance. Basophils dominated the 24-hr challenge feeding sites of A. americanum ticks in actively sensitized hosts (69% of the infiltrate) and recipients of sensitized PEC (69%). Mononuclear cells were dominant (69% of the infiltrate) in the challenged tissues of immune serum recipients that had a significant but weaker cutaneous basophil response (24%). Mononuclear cells also dominated (58% of the infiltrate) the 24-hr challenge feeding sites of R. sanguineus ticks in actively sensitized hosts, but there were also 24% basophils. These studies demonstrate that immune resistance to tick is dependent on sensitized lymphoid cells or serum components, and that sensitized cells or serum can transfer a cutaneous basophil response that is associated with immune resistance. Rejection of ticks is usually associated with large basophil infiltrates, but sometimes mononuclear cells are dominant. Thus, immune resistance of guinea pigs to ticks is a heterogeneous response in which immune cells and serum probably act to recruit diverse effector leukocytes to mediate rejection that is specific but significantly cross-reactive.

  9. Modulation of histamine release from human basophils in vitro by physiological concentrations of zinc

    SciTech Connect

    Marone, G.; Findlay, S.R.; Lichtenstein, L.M.

    1981-05-01

    Zinc, at physiologic concentrations, inhibits in vitro histamine release from human basophils induced by several immunologic (i.e., antigen and anti-immunoglobulin E (IgE) and nonimmunologic (Ca/sup + +/ ionophore A23187 and formylated tripeptide formyl-methionyl-leucyl-phenylalanine (f-met peptide)) stimuli in a dose-dependent manner. Inhibition begins at about 10(-6) (ionophore A23187, anti-IgE and antigen) or 10(-5) M (f-met peptide) and is maximum at 10(-4) M (80--100% inhibition of histamine release). The activity of zinc is about 25-fold greater with respect to ionophore A23187 (ID50 . 1.1 x 10(-6) M) than to f-met peptide-induced (ID50 . 4 x 10(-5) M) histamine release. Its activity on IgE-mediated histamine release is intermediate between these two extremes (ID50 . 9.7 x 10(-6) M). Zinc does not affect the first stage of histamine release but acts on the calcium-dependent second stage. It is a competitive antagonist of the action of Ca/sup + +/ in histamine secretion induced by antigen, anti-IgE and f-met peptide (but not by A23187) with a dissociation constant of about 1.2 x 10(-5) M. The addition of colchicine with zinc fails to increase the inhibition caused by the ion alone, suggesting the two compounds work via a common mechanism of action. Deuterium oxide reversed, in a dose-dependent manner, the inhibition of histamine release caused by zinc. These results suggest that the effect of zinc on histamine release from human basophils may be related to its influence on the microtubule system, directly or via its interaction with calcium.

  10. Basophil Reactivity as Biomarker in Immediate Drug Hypersensitivity Reactions—Potential and Limitations

    PubMed Central

    Steiner, Markus; Harrer, Andrea; Himly, Martin

    2016-01-01

    Immediate drug hypersensitivity reactions (DHRs) resemble typical immunoglobulin E (IgE)-mediated symptoms. Clinical manifestations range from local skin reactions, gastrointestinal and/or respiratory symptoms to severe systemic involvement with potential fatal outcome. Depending on the substance group of the eliciting drug the correct diagnosis is a major challenge. Skin testing and in vitro diagnostics are often unreliable and not reproducible. The involvement of drug-specific IgE is questionable in many cases. The culprit substance (parent drug or metabolite) and potential cross-reacting compounds are difficult to identify, patient history and drug provocation testing often remain the only means for diagnosis. Hence, several groups proposed basophil activation test (BAT) for the diagnosis of immediate DHRs as basophils are well-known effector cells in allergic reactions. However, the usefulness of BAT in immediate DHRs is highly variable and dependent on the drug itself plus its capacity to spontaneously conjugate to serum proteins. Stimulation with pure solutions of the parent drug or metabolites thereof vs. drug-protein conjugates may influence sensitivity and specificity of the test. We thus, reviewed the available literature about the use of BAT for diagnosing immediate DHRs against drug classes such as antibiotics, radio contrast media, neuromuscular blocking agents, non-steroidal anti-inflammatory drugs, and biologicals. Influencing factors like the selection of stimulants or of the identification and activation markers, the stimulation protocol, gating strategies, and cut-off definition are addressed in this overview on BAT performance. The overall aim is to evaluate the suitability of BAT as biomarker for the diagnosis of immediate drug-induced hypersensitivity reactions. PMID:27378928

  11. Threshold for Positivity and Optimal Dipyrone Concentration in Flow Cytometry-Assisted Basophil Activation Test

    PubMed Central

    Longrois, Dan; Petrisor, Cristina

    2013-01-01

    Purpose Basophil activation occurs both in patients with immediate hypersensitivity reactions to anti-inflammatory drugs and in healthy controls in a dose-dependent manner. Our aims were to define the optimal basophil activation test (BAT) concentration and the threshold for BAT positivity for dipyrone. Methods From 45 patients with a positive history of an immediate hypersensitivity reaction to dipyrone, we found 20 patients with dipyrone-induced anaphylaxis demonstrating positive skin tests. All selected patients, as well as 10 healthy controls, were tested in vivo and in vitro. BAT was performed using Flow 2CAST technique with three low dipyrone concentrations: 25 µg/mL (c1), 2.5 µg/mL (c2) and 0.25 µg/mL (c3). The threshold for BAT positivity was established using receiver operating characteristics (ROC) curve analysis. Results Using ROC curve analysis the highest area under curve, 0.79 (0.63-0.95) (P<0.01), was found for c3. When the highest stimulation indexes from the three concentrations for each patient were used, ROC curve analysis revealed an area under curve of 0.81 (0.65-0.96) (P<0.01), sensitivity and specificity were 0.70 and 1 and the optimal threshold value for BAT positivity was 1.71. Thirteen patients had a positive BAT for at least one of the tested dipyrone concentrations. All healthy controls presented negative BAT. Conclusions BAT might be a useful technique to diagnose dipyrone allergy, provided all three low dipyrone concentrations are used together. With an assay-specific threshold of 1.71, ROC curve analysis yields 70% sensitivity and 100% specificity. PMID:24179685

  12. Road map for the clinical application of the basophil activation test in food allergy.

    PubMed

    Santos, A F; Shreffler, W G

    2017-09-01

    The diagnosis of IgE-mediated food allergy based solely on the clinical history and the documentation of specific IgE to whole allergen extract or single allergens is often ambiguous, requiring oral food challenges (OFCs), with the attendant risk and inconvenience to the patient, to confirm the diagnosis of food allergy. This is a considerable proportion of patients assessed in allergy clinics. The basophil activation test (BAT) has emerged as having superior specificity and comparable sensitivity to diagnose food allergy, when compared with skin prick test and specific IgE. BAT, therefore, may reduce the number of OFC required for accurate diagnosis, particularly positive OFC. BAT can also be used to monitor resolution of food allergy and the clinical response to immunomodulatory treatments. Given the practicalities involved in the performance of BAT, we propose that it can be applied for selected cases where the history, skin prick test and/or specific IgE are not definitive for the diagnosis of food allergy. In the cases that the BAT is positive, food allergy is sufficiently confirmed without OFC; in the cases that BAT is negative or the patient has non-responder basophils, OFC may still be indicated. However, broad clinical application of BAT demands further standardization of the laboratory procedure and of the flow cytometry data analyses, as well as clinical validation of BAT as a diagnostic test for multiple target allergens and confirmation of its feasibility and cost-effectiveness in multiple settings. © 2017 The Authors. Clinical & Experimental Allergy published by John Wiley & Sons Ltd.

  13. Transcription factor RBP-J-mediated signalling regulates basophil immunoregulatory function in mouse asthma model.

    PubMed

    Qu, Shuo-Yao; He, Ya-Long; Zhang, Jian; Wu, Chang-Gui

    2017-09-01

    Basophils (BA) play an important role in the promotion of aberrant T helper type 2 (Th2) immune responses in asthma. It is not only the effective cell, but also modulates the initiation of Th2 immune responses. We earlier demonstrated that Notch signalling regulates the biological function of BAin vitro. However, whether this pathway plays the same role in vivo is not clear. The purpose of the present study was to investigate the effect of Notch signalling on BA function in the regulation of allergic airway inflammation in a murine model of asthma. Bone marrow BA were prepared by bone marrow cell culture in the presence of recombinant interleukin-3 (rIL-3; 300 pg/ml) for 7 days, followed by isolation of the CD49b(+) microbeads. The recombination signal binding protein J (RBP-J(-/-) ) BA were co-cultured with T cells, and the supernatant and the T-cell subtypes were examined. The results indicated disruption of the capacity of BA for antigen presentation alongside an up-regulation of the immunoregulatory function. This was possibly due to the low expression of OX40L in the RBP-J(-/-) BA. Basophils were adoptively transferred to ovalbumin-sensitized recipient mice, to establish an asthma model. Lung pathology, cytokine profiles of brobchoalveolar fluid, airway hyperactivity and the absolute number of Th1/Th2 cells in lungs were determined. Overall, our results indicate that the RBP-J-mediated Notch signalling is critical for BA-dependent immunoregulation. Deficiency of RBP-J influences the immunoregulatory functions of BA, which include activation of T cells and their differentiation into T helper cell subtypes. The Notch signalling pathway is a potential therapeutic target for BA-based immunotherapy against asthma. © 2017 John Wiley & Sons Ltd.

  14. Basophil activation test to optimize the diagnosis of adverse effects following immunization to vaccines.

    PubMed

    Chirumbolo, Salvatore

    2013-07-09

    Adverse effects following immunization to vaccines (AEFI) are considered extremely rare events, the occurrence of which could gain a major role in optimizing allergy diagnosis by cellular tests. The urgent need to eradicate infectious diseases from population, is the main goal of vaccination campaign, therefore its successful outcome should be almost undisputable. Basophil Activation Test (BAT) is commonly used to ascertain a type I hypersensitivity reaction, often replacing reasability tests. Therefore, flow cytometry assay of basophil, as performed in BATs, is employed to test if a particular antigen elicits some activatory response from cells. The allergic subject may undergo an AEFI to vaccine not necessarily by an atopic reaction with an allergen within vaccines but because of the existence of an asymptomatic or not diagnosed inflammatory chronic allergy or other immune-disregulating allergy disorder in the subject. BAT, also in its basilar fashion, might be used from a simple heparinized whole blood specimen, but its application in diagnosing allergy before mandatory of facultative vaccination, must be associated to improve other diagnostic tools, at least in its pivotal application. If the application of BAT can be suggested to improve allergy diagnosis by introducing a cellular test in routinely used tools, such as sIgE and SPT, its use, due to possible expertise-consuming and relatively expensive issues, can be included in a specialized allergy consultancy panel as an exploratory approach of allergy inflammation, for which a subject undergoing immunization by vaccines is suggested to undergo and advised to sign an informed consent for BAT performing. This may extend BAT use in many other forms of chronic allergy and immunity disorders related to AEFI with vaccines.

  15. The Family Leukemia Association

    ERIC Educational Resources Information Center

    Pollitt, Eleanor

    1976-01-01

    An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

  16. The Family Leukemia Association

    ERIC Educational Resources Information Center

    Pollitt, Eleanor

    1976-01-01

    An association of families of children with leukemia, the Family Leukemia Association (FLA), was recently established in Toronto. This paper discusses (a) philosophy of the FLA; (b) formative years of this organization; (c) problems encountered by leukemic children and their families; and (d) the FLA's past and future educational and social…

  17. [Acute plasma cell leukemia].

    PubMed

    Monsalbe, V; Domíngues, C; Roa, I; Busel, D; González, S

    1989-01-01

    Plasma Cell Leukemia is a very rare form of plasmocytic dyscrasia, whose clinical and pathological characteristics warrant its recognition as a distinct subentity. We report the case of a 60 years old man who presented a rapidly fatal acute plasma cell leukemia, with multiple osteolytic lesions, hipercalcemia, renal and cardiac failure.

  18. Allergen challenge of peripheral blood mononuclear cells from patients with seasonal allergic rhinitis increases IL-17RB, which regulates basophil apoptosis and degranulation.

    PubMed

    Wang, H; Mobini, R; Fang, Y; Barrenäs, F; Zhang, H; Xiang, Z; Benson, M

    2010-08-01

    Previously, expression profiling has been used to analyse allergen-challenged T-helper type 2 cells, nasal biopsies and nasal fluid cells from patients with seasonal allergic rhinitis (SAR). Allergen-challenged peripheral blood mononuclear cells (PBMCs) provide a human in vitro model of how antigen-presenting cells, CD4+ T cells and effector cells such as basophils interact in allergic inflammation. To identify novel genes and pathways in allergen-challenged PBMCs from patients with SAR using gene expression profiling and functional studies. PBMCs from 11 patients with SAR and 23 healthy controls were analysed with gene expression profiling. mRNA expression of IL17RB in basophils was evaluated using quantitative real-time PCR. Membrane protein expression and apoptosis of basophils were examined by flow cytometry. Degranulation of basophils was assessed by measuring beta-hexosaminidase release. Cytokine release was measured using ELISA. Gene expression microarray analysis of allergen-challenged PBMCs showed that 209 out of 44000 genes were differentially expressed in patients compared with controls. IL17RB was the gene whose expression increased most in patients (P<0.0001). FACS analysis of PBMCs showed, for the first time, that basophils express IL-17RB. Following allergen challenge, IL-17RB protein increased significantly on basophils from patients compared with controls (P<0.05). IL-3 significantly increased both mRNA and protein expressions of IL17RB. Activation of IL-17RB by its ligand, IL-25, inhibited apoptosis of basophils. Moreover, IgE-mediated degranulation was enhanced by IL-25. Increased expression of IL-17RB on allergen-challenged basophil is regulated by IL-3, inhibits apoptosis and promotes IgE-mediated degranulation of basophils.

  19. Fludarabine Phosphate and Total-Body Irradiation Before Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Leukemia

    ClinicalTrials.gov

    2016-07-18

    B-Cell Prolymphocytic Leukemia; Chronic Lymphocytic Leukemia; Prolymphocytic Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; T-Cell Prolymphocytic Leukemia

  20. Leukemia Cutis Associated with Secondary Plasma Cell Leukemia.

    PubMed

    DeMartinis, Nicole C; Brown, Megan M; Hinds, Brian R; Cohen, Philip R

    2017-05-09

    Plasma cell leukemia is an uncommon, aggressive variant of leukemia that may occur de novo or in association with multiple myeloma. Leukemia cutis is the cutaneous manifestation of leukemia, and indicates an infiltration of the skin by malignant leukocytes or their precursors. Plasma cell leukemia cutis is a rare clinical presentation of leukemia. We present a man who developed plasma cell leukemia cutis in association with multiple myeloma. Cutaneous nodules developed on his arms and legs 50 days following an autologous stem cell transplant. Histopathologic examination showed CD138-positive nodular aggregates of atypical plasma cells with kappa light chain restriction, similar to the phenotype of his myeloma. In spite of systemic treatment of his underlying disease, he died 25 days after the presentation of leukemia cutis. Pub-Med was searched for the following terms: cutaneous plasmacytomas, leukemia cutis, plasma cell leukemia nodules, plasma cell leukemia cutis, and secondary cutaneous plasmacytoma. Papers were reviewed and appropriate references evaluated. Leukemia cutis in plasma cell leukemia patients is an infrequent occurrence. New skin lesions in patients with plasma cell leukemia should be biopsied for pathology and for tissue cultures to evaluate for cancer or infection, respectively. The diagnosis plasma cell leukemia cutis is associated with a very poor prognosis.

  1. Assessment of the Sensitizing Potential of Processed Peanut Proteins in Brown Norway Rats: Roasting Does Not Enhance Allergenicity

    PubMed Central

    Kroghsbo, Stine; Rigby, Neil M.; Johnson, Philip E.; Adel-Patient, Karine; Bøgh, Katrine L.; Salt, Louise J.; Mills, E. N. Clare; Madsen, Charlotte B.

    2014-01-01

    Background IgE-binding of process-modified foods or proteins is the most common method for examination of how food processing affects allergenicity of food allergens. How processing affects sensitization capacity is generally studied by administration of purified food proteins or food extracts and not allergens present in their natural food matrix. Objectives The aim was to investigate if thermal processing increases sensitization potential of whole peanuts via the oral route. In parallel, the effect of heating on sensitization potential of the major peanut allergen Ara h 1 was assessed via the intraperitoneal route. Methods Sensitization potential of processed peanut products and Ara h 1 was examined in Brown Norway (BN) rats by oral administration of blanched or oil-roasted peanuts or peanut butter or by intraperitoneal immunization of purified native (N-), heated (H-) or heat glycated (G-)Ara h 1. Levels of specific IgG and IgE were determined by ELISA and IgE functionality was examined by rat basophilic leukemia (RBL) cell assay. Results In rats dosed orally, roasted peanuts induced significant higher levels of specific IgE to NAra h 1 and 2 than blanched peanuts or peanut butter but with the lowest level of RBL degranulation. However, extract from roasted peanuts was found to be a superior elicitor of RBL degranulation. Process-modified Ara h 1 had similar sensitizing capacity as NAra h 1 but specific IgE reacted more readily with process-modified Ara h 1 than with native. Conclusions Peanut products induce functional specific IgE when dosed orally to BN rats. Roasted peanuts do not have a higher sensitizing capacity than blanched peanuts. In spite of this, extract from roasted peanuts is a superior elicitor of RBL cell degranulation irrespectively of the peanut product used for sensitization. The results also suggest that new epitopes are formed or disclosed by heating Ara h 1 without glucose. PMID:24805813

  2. Assessment of the sensitizing potential of processed peanut proteins in Brown Norway rats: roasting does not enhance allergenicity.

    PubMed

    Kroghsbo, Stine; Rigby, Neil M; Johnson, Philip E; Adel-Patient, Karine; Bøgh, Katrine L; Salt, Louise J; Mills, E N Clare; Madsen, Charlotte B

    2014-01-01

    IgE-binding of process-modified foods or proteins is the most common method for examination of how food processing affects allergenicity of food allergens. How processing affects sensitization capacity is generally studied by administration of purified food proteins or food extracts and not allergens present in their natural food matrix. The aim was to investigate if thermal processing increases sensitization potential of whole peanuts via the oral route. In parallel, the effect of heating on sensitization potential of the major peanut allergen Ara h 1 was assessed via the intraperitoneal route. Sensitization potential of processed peanut products and Ara h 1 was examined in Brown Norway (BN) rats by oral administration of blanched or oil-roasted peanuts or peanut butter or by intraperitoneal immunization of purified native (N-), heated (H-) or heat glycated (G-)Ara h 1. Levels of specific IgG and IgE were determined by ELISA and IgE functionality was examined by rat basophilic leukemia (RBL) cell assay. In rats dosed orally, roasted peanuts induced significant higher levels of specific IgE to NAra h 1 and 2 than blanched peanuts or peanut butter but with the lowest level of RBL degranulation. However, extract from roasted peanuts was found to be a superior elicitor of RBL degranulation. Process-modified Ara h 1 had similar sensitizing capacity as NAra h 1 but specific IgE reacted more readily with process-modified Ara h 1 than with native. Peanut products induce functional specific IgE when dosed orally to BN rats. Roasted peanuts do not have a higher sensitizing capacity than blanched peanuts. In spite of this, extract from roasted peanuts is a superior elicitor of RBL cell degranulation irrespectively of the peanut product used for sensitization. The results also suggest that new epitopes are formed or disclosed by heating Ara h 1 without glucose.

  3. A modified method to detect the phagocytic ability of eosinophilic and basophilic haemocytes in the oyster Crassostrea plicatula.

    PubMed

    Lin, Tingting; Zhang, Dong; Lai, Qifang; Sun, Min; Quan, Weimin; Zhou, Kai

    2014-09-01

    The immune defence system of bivalve species largely depends on haemocytes. Haemocytes are generally classified as hyalinocytes (H) or granulocytes (G), and each cell type is further sub-classified as eosinophilic (E) or basophilic (B) haemocytes. Until recently, research on eosinophilic and basophilic haemocytes has primarily focused on their morphologies, dye affinities and intracellular components. Few studies have investigated their phagocytic ability because of the absence of appropriate experimental methods. In this study, we introduce a modified method suitable to detect the phagocytic ability of eosinophilic and basophilic haemocytes. This modified method involves neutral red staining by employing fluorescent microspheres as the phagocytosed medium. Specifically, haemocytes are incubated with fluorescent microspheres and then stained with neutral red. Next, the stained haemocytes are fixed by acetone and are counterstained by propidium iodide. Finally, the haemocytes are observed under a multifunctional microscope to analyse the phagocytic ability by counting the number of eosinophilic or basophilic haemocytes involved in phagocytosis (calculation for phagocytic rate, PR) and the number of phagocytosed microspheres by each eosinophilic or basophilic haemocyte (calculation for phagocytic index, PI). By employing this modified method in the oyster Crassostrea plicatula, we found that the PRs of G and H were very similar to the data obtained by another method, flow cytometry, indicating that this modified method has high accuracy. Additionally, we also found that the PR and PI in E-G were 70.9 ± 7.3% and 1.0 ± 0.2, respectively, which were both significantly higher than those in B-G (53.1 ± 6.4% and 0.7 ± 0.1). The PR and PI in E-H were 16.3 ± 2.8% and 0.2 ± 0.1, respectively, while in B-H, the PR and PI were 13.3 ± 3.6% and 0.2 ± 0.1, respectively, with no significant difference observed. Based on this result, eosinophilic granulocytes are more active

  4. Functional analysis of cross-reactive immunoglobulin E antibodies: peanut-specific immunoglobulin E sensitizes basophils to tree nut allergens.

    PubMed

    de Leon, M P; Drew, A C; Glaspole, I N; Suphioglu, C; Rolland, J M; O'Hehir, R E

    2005-08-01

    Peanut and tree nuts are a major cause of food-induced anaphylaxis with an appreciable mortality. Co-sensitization to peanuts and tree nuts is a common clinical observation and may be because of peanut-specific serum IgE antibodies that cross-react with tree nut allergens. It is, however, unclear whether these cross-reactive IgE antibodies are involved in effector-cell activation. To determine if cross-reactivity of peanut-specific IgE antibodies with tree nuts can cause effector cell activation using an in vitro basophil activation assay. Two peanut allergic subjects with positive specific IgE for peanut and tree nuts (as measured by CAP-FEIA) were studied. Basophil activation to peanut and tree nuts, as indicated by CD63 expression, was assessed by flow cytometry to confirm co-sensitization to peanut and tree nuts. Inhibition ELISA using sera from the subjects was performed to detect peanut-specific IgE antibodies that cross-reacted with tree nut proteins. To determine whether cross-reactive tree nut allergens can induce effector-cell activation, peanut-specific antibodies were affinity purified from the subject sera and used to resensitize non-peanut/tree nut allergic donor basophils stripped of surface IgE. Basophil activation was then measured following stimulation with peanut and tree nut extracts. The two peanut allergic subjects in this study showed positive basophil activation to the peanut and tree nut extracts. Inhibition ELISA demonstrated that pre-incubation of the peanut allergic subject sera with almond, Brazil nut and hazelnut extracts inhibited IgE binding to peanut extract. IgE-stripped basophils from non-peanut/tree nut allergic subjects resensitized with affinity-purified peanut-specific antibodies from the peanut allergic subject sera became activated following stimulation with peanut, almond and Brazil nut extracts, demonstrating biological activity of cross-reactive IgE antibodies. Peanut-specific IgE antibodies that cross-react with tree nut

  5. In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) rat-bovine chimeric antibody against bovine leukemia virus infection

    PubMed Central

    Nishimori, Asami; Okagawa, Tomohiro; Maekawa, Naoya; Ikebuchi, Ryoyo; Goto, Shinya; Sajiki, Yamato; Suzuki, Yasuhiko; Kohara, Junko; Ogasawara, Satoshi; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

    2017-01-01

    Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12). Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL) stage. Cultivation of peripheral blood mononuclear cells (PBMCs) isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application. PMID:28445479

  6. In vitro and in vivo antivirus activity of an anti-programmed death-ligand 1 (PD-L1) rat-bovine chimeric antibody against bovine leukemia virus infection.

    PubMed

    Nishimori, Asami; Konnai, Satoru; Okagawa, Tomohiro; Maekawa, Naoya; Ikebuchi, Ryoyo; Goto, Shinya; Sajiki, Yamato; Suzuki, Yasuhiko; Kohara, Junko; Ogasawara, Satoshi; Kato, Yukinari; Murata, Shiro; Ohashi, Kazuhiko

    2017-01-01

    Programmed death-1 (PD-1), an immunoinhibitory receptor on T cells, is known to be involved in immune evasion through its binding to PD-ligand 1 (PD-L1) in many chronic diseases. We previously found that PD-L1 expression was upregulated in cattle infected with bovine leukemia virus (BLV) and that an antibody that blocked the PD-1/PD-L1 interaction reactivated T-cell function in vitro. Therefore, this study assessed its antivirus activities in vivo. First, we inoculated the anti-bovine PD-L1 rat monoclonal antibody 4G12 into a BLV-infected cow. However, this did not induce T-cell proliferation or reduction of BLV provirus loads during the test period, and only bound to circulating IgM+ B cells until one week post-inoculation. We hypothesized that this lack of in vivo effects was due to its lower stability in cattle and so established an anti-PD-L1 rat-bovine chimeric antibody (Boch4G12). Boch4G12 was able to bind specifically with bovine PD-L1, interrupt the PD-1/PD-L1 interaction, and activate the immune response in both healthy and BLV-infected cattle in vitro. Therefore, we experimentally infected a healthy calf with BLV and inoculated it intravenously with 1 mg/kg of Boch4G12 once it reached the aleukemic (AL) stage. Cultivation of peripheral blood mononuclear cells (PBMCs) isolated from the tested calf indicated that the proliferation of CD4+ T cells was increased by Boch4G12 inoculation, while BLV provirus loads were significantly reduced, clearly demonstrating that this treatment induced antivirus activities. Therefore, further studies using a large number of animals are required to support its efficacy for clinical application.

  7. Leukemias in Children.

    PubMed

    Seth, Rachna; Singh, Amitabh

    2015-09-01

    Childhood cancers are rare but an important cause of morbidity and mortality in children younger than 15 y of age. Common childhood malignancies include leukemias (commonest, 30-40%), brain tumors (20%) and lymphoma (12%) followed by neuroblastoma, retinoblastoma and tumors arising from soft tissues, bones and gonads. Leukemias, the commonest childhood cancer, arise from clonal proliferation of abnormal hematopoietic cells leading to disruption of normal marrow function and marrow failure. The various clinical manifestations of leukemia result from unregulated proliferation of the malignant clone and bone marrow failure. There are two main subtypes, the commoner, acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). A small proportion may have chronic myeloid leukemia (CML) and juvenile myelomonocytic leukemia (JMML). A systematic approach is necessary for diagnosis. Treatment should be initiated as early as possible to avoid complications. A timely referral to a cancer center must be done if facilities for diagnosis/treatment, management of complications and provision for supportive care are not available at the treating center.

  8. Dermatoglyphics in childhood leukemia

    PubMed Central

    Berka, Ludmila; McClure, P. D.; Sonley, Marilyn J.; Thompson, Margaret W.

    1971-01-01

    The dermatoglyphics of 54 leukemic children do not differ significantly from those of 25 mothers and 592 unrelated controls with respect to frequency of digital pattern types, position of axial triradius, or type of palmar flexion creases. These findings do not support the hypothesis that children with leukemia have an increased frequency of unusual dermal patterns, but suggest that the dermatoglyphics of leukemic children are not distinctive and therefore have no practical value in the diagnosis of childhood leukemia. Whatever factors are responsible for the development of leukemia in children, these factors do not appear regularly to affect the differentiation of the dermal ridges. PMID:5112119

  9. Release of platelet-activating factor (PAF) and histamine. II. The cellular origin of human PAF: monocytes, polymorphonuclear neutrophils and basophils.

    PubMed Central

    Camussi, G; Aglietta, M; Coda, R; Bussolino, F; Piacibello, W; Tetta, C

    1981-01-01

    The origin of platelet activating factor (PAF) from human leucocytes was investigated. Purified monocytes release PAF passively at pH 10.6, when challenged with Ionophore A 23187 or under phagocytic stimuli. Pure preparations of polymorphonuclear neutrophils liberate PAF passively, when challenged with C5a, neutrophil cationic proteins (CP), their carboxypeptidase B derived products (C5a des Arg, CP des Arg) or under phagocytic stimuli. Basophil rich buffy coat cells release PAF when challenged with C5a, CP, anti-IgE (in low amount) or Synacthen concomitantly with basophil degranulation and histamine release. Electron microscopy studies, carried out on Synacthen-stimulated basophil rich buffy coat, provide morphological evidence for platelet-basophil interaction. In conclusion our data demonstrate that PAF can be released from different leucocyte populations. However, the stimuli able to trigger such release appear to have some specificity for the cell target. Images Figure 5 PMID:6161885

  10. Acute Myeloid Leukemia (AML) (For Parents)

    MedlinePlus

    ... TV, Video Games, and the Internet Acute Myeloid Leukemia (AML) KidsHealth > For Parents > Acute Myeloid Leukemia (AML) ... Treatment Coping en español Leucemia mieloide aguda About Leukemia Leukemia is a type of cancer that affects ...

  11. Can Acute Myeloid Leukemia Be Prevented?

    MedlinePlus

    ... Causes, Risk Factors, and Prevention Can Acute Myeloid Leukemia Be Prevented? It’s not clear what causes most ... Myeloid Leukemia Be Prevented? More In Acute Myeloid Leukemia About Acute Myeloid Leukemia Causes, Risk Factors, and ...

  12. Heme oxygenase-1 inhibits basophil maturation and activation but promotes its apoptosis in T helper type 2-mediated allergic airway inflammation.

    PubMed

    Zhong, Wenwei; Di, Caixia; Lv, Jiajia; Zhang, Yanjie; Lin, Xiaoliang; Yuan, Yufan; Lv, Jie; Xia, Zhenwei

    2016-03-01

    The anti-inflammatory role of heme oxygenase-1 (HO-1) has been studied extensively in many disease models including asthma. Many cell types are anti-inflammatory targets of HO-1, such as dendritic cells and regulatory T cells. In contrast to previous reports that HO-1 had limited effects on basophils, which participate in T helper type 2 immune responses and antigen-induced allergic airway inflammation, we demonstrated in this study, for the first time, that the up-regulation of HO-1 significantly suppressed the maturation of mouse basophils, decreased the expression of CD40, CD80, MHC-II and activation marker CD200R on basophils, blocked DQ-ovalbumin uptake and promoted basophil apoptosis both in vitro and in vivo, leading to the inhibition of T helper type 2 polarization. These effects of HO-1 were mimicked by exogenous carbon monoxide, which is one of the catalytic products of HO-1. Furthermore, adoptive transfer of HO-1-modified basophils reduced ovalbumin-induced allergic airway inflammation. The above effects of HO-1 can be reversed by the HO-1 inhibitor Sn-protoporphyrin IX. Moreover, conditional depletion of basophils accompanying hemin treatment further attenuated airway inflammation compared with the hemin group, indicating that the protective role of HO-1 may involve multiple immune cells. Collectively, our findings demonstrated that HO-1 exerted its anti-inflammatory function through suppression of basophil maturation and activation, but promotion of basophil apoptosis, providing a possible novel therapeutic target in allergic asthma.

  13. A comparative study on basophil activation test, histamine release assay, and passive sensitization histamine release assay in the diagnosis of peanut allergy.

    PubMed

    Larsen, L F; Juel-Berg, N; Hansen, K S; Clare Mills, E N; van Ree, R; Poulsen, L K; Jensen, B M

    2017-07-07

    Allergy can be diagnosed using basophil tests. Several methods measuring basophil activation are available. This study aimed at comparing basophil activation test (BAT), histamine release assay (HR), and passive sensitization histamine release assay (passive HR) in the diagnosis of peanut allergy. BAT, HR, and passive HR were performed on 11 peanut-allergic and 14 nonallergic subjects. Blood was incubated with peanut extract or anti-IgE and tests were performed as follows: BAT-CD63 upregulation was assessed by flow cytometry; HR-released histamine was quantified by a glass fiber-based fluorometric method; passive HR-IgE-stripped donor basophils were incubated with participants' serum and histamine release was quantified as HR. CDsens, a measure of basophil allergen sensitivity, was significantly higher for BAT (80.1±17.4) compared to HR (23.4±10.31) and passive HR (11.1±2.0). BAT, HR, and passive HR had a clinical sensitivity of 100%, 100%, and 82% and specificity of 100%, 100%, and 100%, respectively, when excluding inconclusive results. BAT identified 11 of 11 allergic patients, HR 10, and passive HR 9. Likewise, BAT recognized 12 of 14 nonallergic subjects, HR 10, and passive HR 13. However, the tests' diagnostic performances were not statistically different. Interestingly, nonreleasers in HR but not in BAT had lower basophil count compared to releasers (249 vs 630 counts/min). BAT displayed a significantly higher CDsens compared to HR and passive HR. The basophil tests' diagnostic performances were not significantly different. Still, BAT could diagnose subjects with low basophil number in contrast to HR. © 2017 EAACI and John Wiley and Sons A/S. Published by John Wiley and Sons Ltd.

  14. Deuterium-oxide-induced histamine release from basophils of allergic subjects. I. Responsiveness to deuterium oxide requires an activation step

    SciTech Connect

    Kazimierczak, W.; Plaut, M.; Knauer, K.A.; Meier, H.L.; Lichtenstein, L.M.

    1984-04-01

    Basophils from many atopic persons, and especially asthmatic patients, have been shown to release histamine in response to 44% deuterium oxide (D2O), whereas basophils from nonatopic persons do not release histamine. The present experiments analyzed the mechanisms by which D/sub 2/O mediated release. It was found that although D/sub 2/O induced release from washed leukocytes, it failed to induce release from whole blood or from leukocytes that had sedimented but had not been washed. The kinetics of release after washing were rapid and were equivalent regardless of the temperature at which cells were sedimented (O degrees or 37 degrees C). Washed cells became desensitized to the action of D/sub 2/O within 30 to 60 min at 37 degrees C, whereas unwashed leukocytes did not become desensitized. Serum or plasma inhibited D/sub 2/O-induced release, although high concentrations (1/5) were less inhibitory than lower ones (1/10 to 1/100). Basophils from D/sub 2/O responders also released histamine in response to a ''platelet enhancing factor'' (PEF), whereas those from D/sub 2/O nonresponders did not. As with D/sub 2/O-mediated release, PEF-mediated release occurred only with washed leukocytes, desensitized within 30 to 60 min at 37 degrees C, and was inhibited by serum. These results suggest that D/sub 2/O induces histamine release by augmenting the effects of an endogenous activation mechanism, and that PEF acts on the same (D/sub 2/O-responsive) donors to augment this activation mechanism. Cell activation, as well as desensitization of this activation mechanism, occurs rapidly when basophils are washed free of plasma inhibitors and placed at 37 degrees C.

  15. Juvenile ALS with basophilic inclusions is a FUS proteinopathy with FUS mutations(e–Pub ahead of print)

    PubMed Central

    Bäumer, D.; Hilton, D.; Paine, S.M.L.; Turner, M.R.; Lowe, J.; Talbot, K.; Ansorge, O.

    2010-01-01

    Background: Juvenile amyotrophic lateral sclerosis (ALS) with basophilic inclusions is a form of ALS characterized by protein deposits in motor neurons that are morphologically and tinctorially distinct from those of classic sporadic ALS. The nosologic position of this type of ALS in the molecular pathologic and genetic classification of ALS is unknown. Methods: We identified neuropathologically 4 patients with juvenile ALS with basophilic inclusions and tested the hypothesis that specific RNA binding protein pathology may define this type of ALS. Immunohistochemical findings prompted us to sequence the fused in sarcoma (FUS) gene. Results: Motor symptoms began between ages 17 and 22. Disease progression was rapid without dementia. No family history was identified. Basophilic inclusions were strongly positive for FUS protein but negative for TAR DNA binding protein 43 (TDP-43). Granular and compact FUS deposits were identified in glia and neuronal cytoplasm and nuclei. Ultrastructure of aggregates was in keeping with origin from fragmented rough endoplasmic reticulum. Sequencing of all 15 exons of the FUS gene in 3 patients revealed a novel deletion mutation (c.1554_1557delACAG) in 1 individual and the c.1574C>T (P525L) mutation in 2 others. Conclusion: Juvenile ALS with basophilic inclusions is a FUS proteinopathy and should be classified as ALS-FUS. The FUS c.1574C>T (P525L) and c.1554_1557delACAG mutations are associated with this distinct phenotype. The molecular genetic relationship with frontotemporal lobar degeneration with FUS pathology remains to be clarified. GLOSSARY ALS = amyotrophic lateral sclerosis; FTLD = frontotemporal lobar degeneration; FTLD-FUS = frontotemporal lobar degeneration with FUS pathology; NIFID = neuronal intermediate filament inclusion disease. PMID:20668261

  16. 377 Test in Vitro to Investigate the Cytotoxicity and Cellular Nonspecific Stimulation of Basophils with Indomethacin

    PubMed Central

    Calamita, Zamir; Antunes, Roseli N. S.; Almeida Filho, Odilon M.; Junior, Wilson Baleotti; Fukasawa, Josianne T.; Cavaretto, Debora A.; Calamita, Andrea B. P.

    2012-01-01

    Background The prevalence of hypersensitivity to nonsteroidal anti-inflammatory drugs (NSAIDs) is high and its in vitro diagnostic is a challenge. The basophil activation test with determination by flow cytometry (FC), of the expression rate of CD63 molecules has been much studied today. NSAIDs several have been evaluated by this technique, which still didn't happen with indomethacin; however, that we may study it is necessary to assess their effects, concentration dependants, on cell viability. We studied the viability of indomethacin dissolved in propylene glycol, analyzing the nonspecific stimulation and cytotoxicity, using in this case the basophil activation test with the use of FC. Methods First it was studied the safe concentration of propylene glycol for dilution of indomethacin, incubating basophils from atopic donor with this diluent. In the second phase, the indomethacin was diluted in the following concentrations: 10 mcg/mL, 1 mcg/mL, 0.1 mcg/mL and the CD63 intensity molecules expression was analysed by FC. Results Regarding the toxicity of propylene glycol, concentrations less than or equal to 0.5% are safe. For indomethacin, the used concentrations (10 mcg/mL, 1 mcg/mL e 0.1 mcg/mL) were viable showing absence of cytotoxicity or nonspecific stimulation. Conclusions Propylene glycol as a diluent of indomethacin is necessary to make at concentrations less than or equal to 0.5%. The indomethacin at concentrations of 10 mcg/mL, 1 mcg/mL and 0.1 mcg/mL proved to be not cytotoxic and without nonspecific stimulant action to basophils.

  17. Drugs Approved for Leukemia

    Cancer.gov

    This page lists cancer drugs approved by the FDA for use in leukemia. The drug names link to NCI's Cancer Drug Information summaries. The list includes generic names, brand names, and common drug combinations, which are shown in capital letters.

  18. Clonal evolution in leukemia.

    PubMed

    Ferrando, Adolfo A; López-Otín, Carlos

    2017-10-06

    Human leukemias are liquid malignancies characterized by diffuse infiltration of the bone marrow by transformed hematopoietic progenitors. The accessibility of tumor cells obtained from peripheral blood or through bone marrow aspirates, together with recent advances in cancer genomics and single-cell molecular analysis, have facilitated the study of clonal populations and their genetic and epigenetic evolution over time with unprecedented detail. The results of these analyses challenge the classic view of leukemia as a clonal homogeneous diffuse tumor and introduce a more complex and dynamic scenario. In this review, we present current concepts on the role of clonal evolution in lymphoid and myeloid leukemia as a driver of tumor initiation, disease progression and relapse. We also discuss the implications of these concepts in our understanding of the evolutionary mechanisms involved in leukemia transformation and therapy resistance.

  19. Monitoring of basophil sensitization to antigens of the cat flea (Ctenocephalides felis felis): a new tool for the diagnosis of feline flea bite hypersensitivity?

    PubMed

    Stuke, K; von Samson-Himmelstjerna, G; Dreesman, J; Mencke, N; Schnieder, T; Leibold, W

    2008-09-01

    Suitability of blood basophils for in vitro diagnosis of flea allergy dermatitis (FAD) or flea bite hypersensitivity was studied in cats. A functional in vitro test (FIT) for sensitized type I allergic effector cells was used to evaluate the degree and kinetics of in vivo basophil sensitization against flea antigens in cats under long-term flea exposure. FIT results were compared with intradermal (IDT) and serological testing. Before, during, and after weekly repeated exposure to Ctenocephalides felis; 14 cats were repetitively FIT-assessed for general and flea-specific sensitization. In three cats, flea-specific sensitization was seen before and throughout flea exposure. Five cats, although generally sensitized, never developed a flea-specific sensitization. Six cats initially FIT-negative became sensitized for flea antigen during flea infestation. Induction, upregulation, and binding of C. felis-specific sensitizing antibodies to basophils during flea challenge may explain the developing sensitization in these cats. Strong discrepancies between the levels of flea-specific circulating IgE and basophil sensitization contrasted comparable results for basophil and mast cell sensitization using FIT and IDT, respectively. Hence, the FIT might provide an immunological supplement to the clinical diagnosis of FAD in cats by elucidating the state of basophil-sensitization to flea antigens. And it may be a comfortable alternative to IDT.

  20. CT findings in leukemia

    SciTech Connect

    Heiberg, E.; Wolverson, M.K.; Sundaram, M.; Shields, J.B.

    1984-12-01

    Review of 84 computed tomographic (CT) scans in leukemic patients demonstrate a wide spectrum of abnormalities. Findings caused by leukemia were lymphadenopathy, visceral enlargement, focal defects, and tissue infiltration. Hemorrhage was by far the most common complication and could usually be characterized on the noncontrast CT scan. The distinction between old hematomas, foci of infection, and leukemia infiltration could not be made with certainty without CT-guided aspiration. Unusual instances of sepsis, such as microabscesses of the liver and typhlitis, were seen.

  1. Model of cell activation and desensitization by surface immunoglobin: the case of histamine release from human basophils

    SciTech Connect

    Dembo, M.; Goldstein, B.

    1980-11-01

    We present a model for the control of immunoglobulin E (IgE)-mediated histamine release from human basophils. We suggest that there is a calcium gating factor which interacts with crosslinked IgE to form a short-lived open calcium channel. After formation of the channel the activated gating factor rapidly decays to an inactive form. It is the loss of the active gating factor which causes the basophil to desensitize nonspecifically. We propose that the crosslinked IgE molecules are deactivated by a mechanism, such as endocytosis or shedding, which is independent of the mechanism which inactivates the calcium gating factor. This loss of functional IgE leads to specific desensitization. The mathematical formulation of the model explains the relationship of specific and nonspecific desensitization to the amount of specific IgE on the basophil surface; explains why there are two types of antigen excess inhibition; explains the relationship between antigen excess inhibition and desensitization; explains why, for a fixed antigen concentration, increasing the concentration of cell surface IgE increases histamine release until an optimal concentration is reached, then decreases histamine release; predicts the effects that changing the external calcium will have on the dose response curve; and predicts that increasing the amount of specific IgE on the cell surface will cause the dose response curve to undergo a transition from a curve with a single maximum to a curve with two maxima.

  2. Treatment of Children with APL (Acute Promyelocytic Leukemia)

    MedlinePlus

    ... Childhood Leukemia Treatment of Children With Acute Promyelocytic Leukemia (APL) Treatment of acute promyelocytic leukemia (APL), the ... With Chronic Myelogenous Leukemia (CML) More In Childhood Leukemia About Childhood Leukemia Causes, Risk Factors, and Prevention ...

  3. Treatment of Chronic Lymphocytic Leukemia by Risk Group

    MedlinePlus

    ... Chronic Lymphocytic Leukemia Typical Treatment of Chronic Lymphocytic Leukemia Treatment options for chronic lymphocytic leukemia (CLL) vary ... Treating Hairy Cell Leukemia More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  4. Apparent posttranscriptional block to anaerobic induction of endogenous leukemia virus.

    PubMed Central

    Whitaker-Dowling, P A; Marotti, K R; Anderson, G R

    1979-01-01

    Uninfected Fischer rat cells were induced by anaerobic stress to transcribe high levels of endogenous type C leukemia virus RNA. Complete 35S virus RNA with attached polyadenylic acid sequences was found associated with polysomes, indicating functional mRNA. Since no mature virus was released under these conditions, the presence of a posttranscriptional block to complete virus synthesis is strongly indicated. PMID:232174

  5. Myeloid leukemia after hematotoxins

    SciTech Connect

    Larson, R.A.; LeBeau, M.M.; Vardiman, J.W.; Rowley, J.D.

    1996-12-01

    One of the most serious consequences of cancer therapy is the development of a second cancer, especially leukemia. Several distinct subsets of therapy-related leukemia can now be distinguished. Classic therapy-related myeloid leukemia typically occurs 5 to 7 years after exposure to alkylating agents and/or irradiation, has a myelodysplastic phase with trilineage involvement, and is characterized by abnormalities of the long arms of chromosomes 5 and/or 7. Response to treatment is poor, and allogeneic bone marrow transplantation is recommended. Leukemia following treatment with agents that inhibit topoisomerase 11, however, has a shorter latency, no preleukemic phase, a monoblastic, myelomonocytic, or myeloblastic phenotype, and balanced translocations, most commonly involving chromosome bands 11 q23 or 21 q22. The MLL gene at 11 q23 or the AML1 gene at 21 q22 are almost uniformly rearranged. MLL is involved with many fusion gene partners. Therapy-related acute lymphoblastic leukemia also occurs with 1 1 q23 rearrangements. Therapy-related leukemias with 11 q23 or 21 q22 rearrangements, inv(16) or t(15;17), have a more favorable response to treatment and a clinical course similar to their de novo counterparts. 32 refs., 4 tabs.

  6. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  7. Use of basophil activation test in the investigation of adverse effects to vaccines.

    PubMed

    Chirumbolo, Salvatore

    2011-08-01

    Diagnosis of adverse effects caused by vaccines mainly includes investigative approaches based on skin tests, histamine, tryptase and serum IgE levels which should allow to diagnose an IgE-mediated allergy reaction, most caused by additive components. Incidence of vaccine-related allergy and anaphylaxis due to vaccination are very poorly represented among population, based on the latest epidemiological and safety reports. Notwithstanding, routinely allergy diagnostic tools show many pitfalls and contradictory results when used to highlight an allergy onset or a clinical manifestation recalling an hypersensitivity reaction. Furthermore, adjuvants in vaccines may trigger innate cells response by toll-like receptors, thus eliciting a possible non-IgE mediated allergy phenomenon or causing B-cell activation and autoimmunity. A cellular test, such as a basophil activation test, or more widely a flow cytometry analysis of immune cells, might add new insights to the comprehension of allergy due to vaccination , thus ameliorating the diagnostic endowment in the hand of physicians.

  8. The history of mast cell and basophil research - some lessons learnt from the last century.

    PubMed

    Blank, U; Falcone, F H; Nilsson, G

    2013-09-01

    This year (2013) marks the 50th anniversary of death of Otto Carl Willy Prausnitz (1876-1963) and Heinz Küstner (1897-1963). The two physicians, when working at the Hygiene Institute at the University of Breslau, Germany (Prausnitz was the Head of the Institute), described in 1921 what is still called today the Prausnitz-Küstner or PK reaction showing that allergy could be transferred from the allergic person by transferring serum to a healthy person. Their discovery ended the belief that an anaphylactic/allergic reaction was caused by poisons, but to the contrary showed that the presence of the hypersensitivity factor could be transferred to other people. We know now that this factor is immunoglobulin E (IgE), sensitizing mast cells and basophils to respond to an allergic stimulus. We take this occasion to retrace some of the important discoveries and lessons learnt from the last century relating to the function of these two cell types as effectors of the IgE system and the mediators they produce.

  9. Serum Specific IgE to Thyroid Peroxidase Activates Basophils in Aspirin Intolerant Urticaria.

    PubMed

    Shin, Yoo Seob; Suh, Dong-Hyeon; Yang, Eun-Mi; Ye, Young-Min; Park, Hae-Sim

    2015-06-01

    Thyroid antibodies are frequently observed in urticaria patients, but their roles in urticaria are not clearly elucidated. We investigated the role of serum specific IgE to thyroid peroxidase (TPO) in patients with aspirin intolerant acute urticaria (AIAU) and aspirin intolerant chronic urticaria (AICU). We recruited 59 AIAU and 96 AICU patients with 69 normal controls (NC). Serum specific IgE to TPO was measured by manual direct ELISA, and CD203c expressions on basophil with additions of TPO were measured to prove a direct role of TPO in effector cells. The prevalences of serum specific IgE to TPO were significantly higher in AIAU (15.2%) and AICU groups (7.5%) compared to NC (0%, P=0.018: P=0.013, respectively). Flow cytometry showed CD203c induction in a dose dependent manner with serial additions of TPO in some AIAU and AICU patients having high specific IgE to TPO. Our findings show that the prevalence of serum specific IgE to TPO was significantly higher in both AIAU and AICU patients than in NC. It is suggested that specific IgE to TPO play a pathogenic role in AIAU and AICU.

  10. [Modified tests basophil degranulation and leukocyte migration inhibition factor in drug allergy. Study 2009-2014].

    PubMed

    Irigoyen-Coria, María Lourdes; Rojo-Gutiérrez, María Isabel; Meyer-Gómez, Rubén Humberto; Leyva-Carmona, Isabel; Zendejas-Buitrón, Víctor Manuel; García-Ruiz, Angélica Dinorah; Mellado-Ábrego, Jaime; García-Ortega, Ilayalid; Castillo-Narváez, Gloria

    2016-01-01

    Adverse reactions to drugs are increasing and there are few studies for the diagnosis. To determine the utility of modified basophil degranulation (MBD) test and modified leukocyte migration inhibition factor (MLMIF) test to prove drug hypersensitivity. 177 patients of both sexes were studied with the diagnosis of drug hypersensitivity, determining MBD, MLMIF, or both, between 2009 and 2014. They were matched with positive and negative controls and the non-allergic population. Applications are issued according to the type of hypersensitivity, considering type I MBD and type IV MLMIF. 170 patients (96.04%) were positive to at least one drug (RR = 4.71). 561 MBD (73.62%) and 201 MLMIF (26.37%) were performed. Female sex was more frequent (64.41%); the average age was 38.5. MBD was positive in 70.23% and MLMIF in 67.16%. The test sensitivity was increased complementarily and with two dilutions. The correlation of MBD and MLMIF was positive and highly significant. Women have more drug reactions. Modified MBD test is useful at any age. Since medications can activate one or other hypersensitivity mechanism, it is important to request the tests simultaneously.

  11. Flavopiridol and Vorinostat in Treating Patients With Relapsed or Refractory Acute Leukemia or Chronic Myelogenous Leukemia or Refractory Anemia

    ClinicalTrials.gov

    2013-04-01

    Blastic Phase Chronic Myelogenous Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  12. Differential release of mediators from human basophils: Differences in arachidonic acid metabolism following activation by unrelated stimuli

    SciTech Connect

    Warner, J.A.; Peters, S.P.; Lichtenstein, L.M.; Hubbard, W.; Yancey, K.B.; Stevenson, H.C.; Miller, P.J.; MacGlashan, D.W. Jr.

    1989-06-01

    We have examined the release of histamine and LTC4 from purified human basophils challenged with several different stimuli, both physiological and nonphysiological. Basophils (n = 16) challenged with 0.1 micrograms/ml anti-IgE released 38 +/- 4% of their available histamine and 39 +/- 12 ng LTC4/10(6) basophils within 15-30 min. F-Met peptide (n = 8) caused the release of 54 +/- 8% histamine and 42 +/- 25 ng LTC4/10(6) basophils within a period of 2-5 min. C5a caused the release of 22 +/- 3% histamine from selected donors but failed to initiate any LTC4 release unless combined with D2O or 5 mM extracellular calcium. The two nonphysiological stimuli A23187 and TPA caused extensive histamine release, 67 +/- 8 and 82 +/- 11%, respectively, and while A23187 initiated a large and rapid release of leukotriene, TPA failed to release any LTC4 even when combined with D2O or 2-5 mM extracellular calcium. Increased concentrations of extracellular calcium enhanced anti-IgE and f-Met peptide induced release of LTC4 but inhibited the A23187 induced release of leukotriene. A single peak of immunoreactive leukotriene C4 that comigrated with the authentic standard was identified using HPLC followed by radioimmunoassay. No LTD4 or LTE4 could be detected. Purified human basophils incubated with 0.2 microM (3H)AA incorporated 290 pmol/10(6) cells, or 32 +/- 5% of the available label within 60 min. The (3H)AA was taken principally into the phospholipids (73 +/- 5%), with 20 +/- 3% as neutral lipid, and only 5 +/- 2% remaining as the free acid. Three phospholipid subclasses, phosphatidylcholine, PC (24 +/- 2%), phosphatidylinositol, PI (22 +/- 1%), and phosphatidylethanolamine, PE (15 +/- 3%), accounted for the majority of the incorporated (3H)AA while the remainder of the phospholipids accounted for less than 5% of the total cpm.

  13. Basophil activation after nonsteroidal anti-inflammatory drugs stimulation in patients with immediate hypersensitivity reactions to these drugs.

    PubMed

    Ariza, Adriana; Fernandez, Tahia D; Doña, Inmaculada; Aranda, Ana; Blanca-Lopez, Natalia; Melendez, Lidia; Canto, Gabriela; Blanca, Miguel; Torres, Maria J; Mayorga, Cristobalina

    2014-05-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) are the drugs most frequently involved in allergic reactions of which two main types exist: IgE-mediated and crossintolerance. The diagnosis of crossintolerance reactions is often based on the drug provocation test. The potential value of the basophil activation test (BAT) was evaluated using different basophil markers in the diagnosis of patients with crossintolerance to NSAIDs and cutaneous symptoms. We studied 46 patients with crossintolerance to NSAIDs and 45 tolerant controls. BAT was performed with acetyl salicylic acid, paracetamol, diclofenac, dipyrone, naproxen, and ibuprofen at four different concentrations using CD193 and CD203c as basophil markers and CD63 as activation marker. We compared BAT results using CD193⁺ or CD193⁺ CD203c⁺ for basophil selection and found a significant increase in the stimulation index when using CD193⁺ CD203c⁺ in both patients and controls (P = 0.004 and P = 0.017, respectively). Selection of living cells only produced an increase in basophil stimulation in patients for both CD193⁺ and CD193⁺ CD203c⁺ (P < 0.001 for both), whereas in controls there was no change with CD193⁺ and a decrease with CD193⁺ CD203c⁺ (P = 0.001). We found that CD193⁺ CD203c⁺ increased the percentage of positive cases in patients and controls when compared with CD193⁺. When excluding dead cells, there was an increase of 21.7% in patients and 10% in controls. These results indicate that using CD193⁺ CD203⁺, excluding dead cells, is the best approach for BAT although this test is not recommended for the diagnosis of patients with crossintolerance to NSAIDs owing to its low sensitivity and specificity.

  14. Anticipation in familial leukemia

    SciTech Connect

    Horwitz, M.; Jarvik, G.P.; Goode, E.L.

    1996-11-01

    Anticipation refers to worsening severity or earlier age at onset with each generation for an inherited disease and primarily has been described for neurodegenerative illnesses resulting from expansion of trinucleotide repeats. We have tested for evidence of anticipation in familial leukemia. Of 49 affected individuals in nine families transmitting autosomal dominant acute myelogenous leukemia (AML), the mean age at onset is 57 years in the grandparental generation, 32 years in the parental generation, and 13 years in the youngest generation (P < .001). Of 21 parent-child pairs with AML, 19 show younger ages at onset in the child and demonstrate a mean decline in age at onset of 28 years (P < .001). Of 18 affected individuals from seven pedigrees with autosomal dominant chronic lymphocytic leukemia (CLL), the mean age at onset in the parental generation is 66 years versus 51 years in the youngest generation (P = .008). Of nine parent-child pairs with CLL, eight show younger ages at onset in the child and reveal a mean decline in age at onset of 21 years (P = .001). Inspection of rare pedigrees transmitting acute lymphocytic leukemia, chronic myelogenous leukemia, multiple types of leukemia, and lymphoma is also compatible with anticipation. Sampling bias is unlikely to explain these findings. This suggests that dynamic mutation of unstable DNA sequence repeats could be a common mechanism of inherited hematopoietic malignancy with implications for the role of somatic mutation in the more frequent sporadic cases. We speculate on three possible candidate genes for familial leukemia with anticipation: a locus on 21q22.1-22.2, CBL2 on 11q23.3, and CBFB or a nearby gene on 16q22. 55 refs., 4 figs.

  15. Topoisomerase II and leukemia

    PubMed Central

    Pendleton, MaryJean; Lindsey, R. Hunter; Felix, Carolyn A.; Grimwade, David; Osheroff, Neil

    2014-01-01

    Type II topoisomerases are essential enzymes that modulate DNA under- and overwinding, knotting, and tangling. Beyond their critical physiological functions, these enzymes are the targets for some of the most widely prescribed anticancer drugs (topoisomerase II poisons) in clinical use. Topoisomerase II poisons kill cells by increasing levels of covalent enzyme-cleaved DNA complexes that are normal reaction intermediates. Drugs such as etoposide, doxorubicin, and mitoxantrone are frontline therapies for a variety of solid tumors and hematological malignancies. Unfortunately, their use is also associated with the development of specific leukemias. Regimens that include etoposide or doxorubicin are linked to the occurrence of acute myeloid leukemias that feature rearrangements at chromosomal band 11q23. Similar rearrangements are seen in infant leukemias and are associated with gestational diets that are high in naturally occurring topoisomerase II–active compounds. Finally, regimens that include mitoxantrone and epirubicin are linked to acute promyelocytic leukemias that feature t(15;17) rearrangements. The first part of this article will focus on type II topoisomerases and describe the mechanism of enzyme and drug action. The second part will discuss how topoisomerase II poisons trigger chromosomal breaks that lead to leukemia and potential approaches for dissociating the actions of drugs from their leukemogenic potential. PMID:24495080

  16. Basophil activation test discriminates between allergy and tolerance in peanut-sensitized children.

    PubMed

    Santos, Alexandra F; Douiri, Abdel; Bécares, Natalia; Wu, Shih-Ying; Stephens, Alick; Radulovic, Suzana; Chan, Susan M H; Fox, Adam T; Du Toit, George; Turcanu, Victor; Lack, Gideon

    2014-09-01

    Most of the peanut-sensitized children do not have clinical peanut allergy. In equivocal cases, oral food challenges (OFCs) are required. However, OFCs are laborious and not without risk; thus, a test that could accurately diagnose peanut allergy and reduce the need for OFCs is desirable. To assess the performance of basophil activation test (BAT) as a diagnostic marker for peanut allergy. Peanut-allergic (n = 43), peanut-sensitized but tolerant (n = 36) and non-peanut-sensitized nonallergic (n = 25) children underwent skin prick test (SPT) and specific IgE (sIgE) to peanut and its components. BAT was performed using flow cytometry, and its diagnostic performance was evaluated in relation to allergy versus tolerance to peanut and validated in an independent population (n = 65). BAT in peanut-allergic children showed a peanut dose-dependent upregulation of CD63 and CD203c while there was no significant response to peanut in peanut-sensitized but tolerant (P < .001) and non-peanut-sensitized nonallergic children (P < .001). BAT optimal diagnostic cutoffs showed 97% accuracy, 95% positive predictive value, and 98% negative predictive value. BAT allowed reducing the number of required OFCs by two-thirds. BAT proved particularly useful in cases in which specialists could not accurately diagnose peanut allergy with SPT and sIgE to peanut and to Arah2. Using a 2-step diagnostic approach in which BAT was performed only after equivocal SPT or Arah2-sIgE, BAT had a major effect (97% reduction) on the number of OFCs required. BAT proved to be superior to other diagnostic tests in discriminating between peanut allergy and tolerance, particularly in difficult cases, and reduced the need for OFCs. Copyright © 2014. Published by Elsevier Inc.

  17. Obatoclax, Fludarabine, and Rituximab in Treating Patients With Previously Treated Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-09-27

    B-cell Chronic Lymphocytic Leukemia; Leukemia; Prolymphocytic Leukemia; Refractory Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage IV Chronic Lymphocytic Leukemia

  18. RUNX1-ETO Leukemia.

    PubMed

    Lin, Shan; Mulloy, James C; Goyama, Susumu

    2017-01-01

    AML1-ETO leukemia is the most common cytogenetic subtype of acute myeloid leukemia, defined by the presence of t(8;21). Remarkable progress has been achieved in understanding the molecular pathogenesis of AML1-ETO leukemia. Proteomic surveies have shown that AML-ETO forms a stable complex with several transcription factors, including E proteins. Genome-wide transcriptome and ChIP-seq analyses have revealed the genes directly regulated by AML1-ETO, such as CEBPA. Several lines of evidence suggest that AML1-ETO suppresses endogenous DNA repair in cells to promote mutagenesis, which facilitates acquisition of cooperating secondary events. Furthermore, it has become increasingly apparent that a delicate balance of AML1-ETO and native AML1 is important to sustain the malignant cell phenotype. Translation of these findings into the clinical setting is just beginning.

  19. Transmission of a Filterable Agent from Rat Leukaemia Induced by X-Ray Irradiation and Treatment with Methylcholanthrene

    SciTech Connect

    Sveg, F.; Hlavay, E.

    2004-07-01

    Leukemia was induced in rats by combination of x irradiation and oral application of methylcholanthrene. The rats were irradiated by a single dose of 800 r, and methylcholanthrene was applied 3 times a week by stomach tube in a dose of 1 mg for 9 months. From 60 rats, myelogenous leukemia developed in 2 and lymphatic leukemia in 1. The myelobiastic leukemia proved to be transplantable and was maintained as MR-leukemia. After irtravenous injection of 1 to 10 x 10/ sup 6/ leukemic cells, obtained from the liver and spleen, the disease developed in adult rats in 6 to 10 days. As early as the 2nd or 3rd day after inoculation, leukemic infiltration of organs, especially liver and spleen, were seen. The rats died exhibiting signs of generalized leukemia within 10 days. If cell-free filtrates from the liver and spleen of rats bearing MR leukemia were injected into newborn and 4-week-old rats, myelogenous leukemia developed in the newborn group in 24% after a latency period of 520 days and in 33% of the 4-week-old group after 570 days, on an average. The induced leukemias were transplantable into both suckling and adult rats. Many of the injected animals, which did not develop leukemia, died of cirrhosis of the liver. The results suggest that the leukemia induced by irradiation and chemical carcinogen might be caused by a submicroscopic virus-like agent.

  20. Leukemia in benzene workers.

    PubMed

    Rinsky, R A; Young, R J; Smith, A B

    1981-01-01

    To evaluate the possible association between occupational exposure to benzene and subsequent death from leukemia, the National Institute for Occupational Safety and Health (NIOSH) conducted a retrospective cohort mortality study of workers who had been exposed to benzene in the manufacture of rubber hydrochloride at two locations in Ohio. Ascertainment of vital status was accomplished for 98% of the cohort. Among 748 workers who had at least one day of exposure to benzene between 1940 and 1950, seven deaths from leukemia occurred; from United States death rates standardized for sex, age, and calendar time period, only 1.25 leukemia deaths would have been expected (standardized mortality ratio = 560; p less than 0.001). Mean duration of exposure to benzene was brief, and 437 (58%) of the cohort were exposed for less than 1 year. Evaluation of leukemia mortality for those workers exposed five or more years showed an SMR of 2100. All leukemia deaths were myelocytic or monocytic in cell type. Four additional cases of leukemia have been reorganized in workers at the study locations, but occurred in persons not encompassed by the strict definition of the cohort. Reconstruction of past exposures to benzene at the two locations indicates that in some areas of the plant airborne benzene concentrations rose occasionally to several hundred parts per million (ppm), but that for the most part, employee eight-hour time-weighted averages (TWA) fell within the limits considered permissible at the time of exposure. These data corroborate an initial analysis of the same cohort by Infante et al, and indicate that benzene is a human carcinogen at a range of exposures not greatly above the current legal standard.

  1. Chronic myelogenous leukemia: a multivariate analysis of the associations of patient characteristics and therapy with survival.

    PubMed

    Kantarjian, H M; Smith, T L; McCredie, K B; Keating, M J; Walters, R S; Talpaz, M; Hester, J P; Bligham, G; Gehan, E; Freireich, E J

    1985-12-01

    The prognostic importance of patient pretreatment clinical and laboratory features was investigated in a group of 303 patients with Philadelphia chromosome-positive benign-phase chronic myelogenous leukemia. Intensive chemotherapy was given to 97 patients, and 78 underwent an early elective splenectomy. The overall median survival time, dated from hospital admission, was 39 months. Patient characteristics associated with shortened survival were age 60 years or older, black race, the presence of hepatomegaly, splenomegaly, symptoms, weight loss, and poor performance status. Adverse blood and bone marrow parameters were anemia, thrombocytosis or thrombocytopenia, a high proportion of peripheral blasts plus promyelocytes or of basophils, a high proportion of marrow blasts or basophils, decreased marrow megakaryocytes, and cytogenetic abnormalities in addition to the Philadelphia chromosome. Several of these factors were interrelated. A multivariate regression analysis demonstrated that the combination blood basophilia, race, additional cytogenetic abnormalities, age and marrow basophilia had the strongest predictive relationship to survival time. This resulted in a model segregating patients into low-, intermediate-, and high-risk groups, with median survivals of 53, 39, and 25 months, respectively. Another model was derived that did not include the marrow features and identified splenomegaly and platelet counts as adding to the prognosis prediction by blood basophilia, race, and age. Evaluation of the effect of therapy, after adjusting for differences in prognostic characteristics, showed that intensive chemotherapy was associated with survival prolongation among patients at intermediate and high risk of death. We conclude that a combination of pretreatment factors identifies different risk subcategories in patients with chronic myelogenous leukemia and is helpful in assessing overall prognosis and treatment effect.

  2. Host basophils are dispensable for induction of donor T helper 2 cell differentiation and severity of experimental graft-versus-host disease.

    PubMed

    Tawara, Isao; Nieves, Evelyn; Liu, Chen; Evers, Rebecca; Toubai, Tomomi; Sun, Yaping; Alrubaie, Mariem; Reddy, Pavan

    2011-12-01

    Host hematopoietic-derived antigen-presenting cells are important for induction of graft-versus-host disease (GVHD). The relative importance of various subsets of hematopoietic-derived antigen-presenting cells is not well understood. Recent data suggest that basophils can function as antigen-presenting cells and induce T helper 2 (Th2) lymphocyte responses. We investigated the role of host basophils in the induction of donor T cell responses and GVHD after allogeneic bone marrow transplantation. Elimination of host basophils did not alter the severity of GVHD-induced mortality across multiple clinically relevant models of allogeneic bone marrow transplantation. Furthermore, induction of donor T cell proliferation and Th2 polarization was not altered significantly after depletion of host basophils. Our results demonstrate that, in contrast to their role in inducing Th2 responses in certain contexts, basophils are dispensable for the induction of donor Th2 responses and for the severity of GVHD. Copyright © 2011 American Society for Blood and Marrow Transplantation. Published by Elsevier Inc. All rights reserved.

  3. Hypersensitivity to fluoroquinolones: The expression of basophil activation markers depends on the clinical entity and the culprit fluoroquinolone.

    PubMed

    Fernández, Tahia D; Ariza, Adriana; Palomares, Francisca; Montañez, María I; Salas, María; Martín-Serrano, Angela; Fernández, Rubén; Ruiz, Arturo; Blanca, Miguel; Mayorga, Cristobalina; Torres, María J

    2016-06-01

    Although fluoroquinolones (FQs) are generally well-tolerated antibiotics, increasing numbers of hypersensitivity reactions have been reported. These can be evaluated in vitro by basophil activation tests (BATs); however, sensitivity is not optimal. Many factors could influence sensitivity such as basophil activation markers. The objective of this study was to evaluate the influence of 2 different activations markers, CD63 and CD203c, on the sensitivity of BAT to FQ. We studied 17 patients with immediate allergic reactions to FQ. BAT was performed with moxifloxacin and ciprofloxacin using CD193 (CCR3) for basophil selection and CD203c or CD63 as activation markers. Stimulation with ciprofloxacin induced a significantly higher expression of CD63 in ciprofloxacin-allergic patients compared to moxifloxacin-allergic patients (P = 0.002). In patients allergic to moxifloxacin with anaphylactic shock, we have observed an increase in the percentage of cells that upregulate CD203c, whereas patients with anaphylaxis preferentially upregulate CD63. The best sensitivity-specificity was obtained using a cutoff of 3 and the culprit FQ, using CD203c for moxifloxacin-allergic patients (sensitivity = 36.4%; specificity = 94.4%), and CD63 for ciprofloxacin-allergic patients (sensitivity = 83.3%; specificity = 88.9%). A negative correlation was found between the upregulation of CD63 and CD203c and the time interval between the reaction occurrence and the performance of the test (Spearman r = -0.446; P < 0.001 for CD63 and Spearman r = -0.386; P < 0.001 for CD203c). The performance of BAT for FQ allergy must be optimized for each drug, taking into account possible differences in the stimulation mechanism that leads to the upregulation of different activation markers.

  4. Basophil activation test in the diagnosis and monitoring of mastocytosis patients with wasp venom allergy on immunotherapy.

    PubMed

    Bidad, Katayoon; Nawijn, Martijn C; van Oosterhout, Antoon J M; van der Heide, Sicco; Elberink, Joanne N G Oude

    2014-05-01

    There is need for an accurate diagnostic test in mastocytosis patients with wasp venom allergy (WVA) and monitoring of these patients during immunotherapy (IT). In this study, we aimed to evaluate sensitivity and specificity of the Basophil Activation Test (BAT) as a diagnostic and monitoring test in patients with mastocytosis and WVA. Seventeen patients with mastocytosis and WVA and six mastocytosis patients without WVA were included. BAT was performed before the start of IT (first visit) and at 6 weeks (second visit) and 1 year (third visit), after reaching the maintenance dose. Of 17 patients included, 11 completed the third visit. In mastocytosis patients with WVA, dose-dependent wasp-venom induced upregulation of CD63 and CD203c expression on basophils was observed compared with mastocytosis patients without WVA. Serum specific IgE, IgG4, and tryptase levels were measured in all patients. BAT had a sensitivity of 87% and specificity of 100% in diagnosing WVA in mastocytosis patients. Basophil allergen threshold sensitivity with respect to CD63 and CD203c was significantly decreased in the second visit compared with the first visit and increased significantly in the third visit compared with the second visit. Specific IgE levels increased significantly in the second visit compared with first and decreased significantly in the third visit compared with the second. Specific IgG4 levels rose significantly in the second visit compared with the first and on the third visit compared with the second. Tryptase levels did not change significantly during the study. BAT represents a diagnostic test with 100% specificity in allergic patients with mastocytosis and these patients are better to be monitored for a longer period during IT. © 2013 Clinical Cytometry Society.

  5. Viral basophilic inclusions in the digestive gland of razor clams Ensis arcuatus (Pharidae) in Galicia (NW Spain).

    PubMed

    Ruiz, M; Darriba, S; Rodríguez, R; Iglesias, D; Lee, R; López, C

    2011-05-09

    During a histological survey of razor clam Ensis arcuatus (Jeffreys, 1865) from Galicia (NW Spain), basophilic inclusion bodies were observed in epithelial cells of the digestive gland. Transmission electron microscopy revealed the intranuclear position of these inclusions containing viral particles with icosahedral symmetry. Size and symmetry of these unenveloped virus particles suggest similarities to the families Papillomaviridae and Polyomaviridae which have been described as causing a viral gametocytic hypertrophy in oysters Crassostrea virginica and C. gigas. This is the first report of viral particles in E. arcuatus.

  6. Impact of allergic rhinitis and specific subcutaneous immunotherapy on peripheral blood basophils of patients sensitized to Dermatophagoides pteronyssinus

    PubMed Central

    2013-01-01

    Background Basophils are important effectors cells in allergic rhinitis (AR) since they are involved in immunoglobulin (Ig) E – mediated inflammation and in the release of pro-inflammatory mediators. Specific subcutaneous immunotherapy (SCIT) provides clear immunologic modulation in some immune cells, however its systemic effects on basophils are not well known. Methods Peripheral blood (PB) samples from 43 patients with allergic rhinitis mono-sensitized to Dermatophagoides pteronyssinus (Dpt) [33 of them under SCIT with allergoid Dpt extract, in maintenance dose (SCIT), with evaluation just before SCIT injection (SCIT-T0) and 4 hours later (SCIT-T4) and the other 10 Dpt allergic patients never having, in the past, undergone specific immunotherapy treatment (NSIT)], and 15 healthy age- and gender-matched controls (HG), were analyzed. For each sample, the total (t-IgE) and specific IgE (s-IgE) was performed, as well as, the relative frequency and absolute number of PB basophils and receptor-bound IgE and IgG expression were evaluated by flow cytometry and the Histamine N-methyltransferase (HNMT) and tryptase α/β1 (TPSAB1) gene expression was assessed by real-time PCR. Results Higher levels of receptor-bound IgE were observed in SCIT patients, which are correlated with the levels of serum t-IgE and s-IgE, whereas no significant differences were observed for receptor-bound IgG. Regarding HNMT mRNA expression, significantly lower expression levels were detected in AR patients compared to HG, independently of type of therapy. Moreover a negative correlation was found between HNMT gene expression and time under SCIT. Conversely, tryptase gene expression was significantly up-regulated in NSIT when compared to HG; however in SCIT patients, tryptase gene expression was significantly decreased than in NSIT patients. No differences were found for any parameter between SCIT-T0 and SCIT-T4 with exception of a transient increased expression of tryptase in SCIT-T4

  7. In vitro histamine release from basophils of asthmatic and atopic individuals in D/sub 2/O

    SciTech Connect

    Tung, R.; Lichtenstein, L.M.

    1982-05-01

    It was found that spontaneous histamine release from human basophils in H/sub 2/O-based buffers is negligible; in D/sub 2/O-based buffers, however, release is observed with the cells of some donors. Analysis of this phenomenon revealed release from the basophils of 1 of 22 control individuals (5%), 15 of 47 patients with allergic rhinitis (32%), and 14 of 20 asthmatic patients (70%). The difference between both patient groups and controls and between atopics and asthmatics was highly significant. That D/sub 2/O release was not cytotoxic is suggested by the finding that 37/sup 0/ was optimal, with inhibition at 4/sup 0/C or 46/sup 0/C as well as by EDTA, 2-deoxyglucose, and dibromoacetophenone, an inhibitor of phospholipase A/sub 2/. The release mechanism was unusual in that dibutyryl cAMP and agonists that cause an increase in cAMP lead to no inhibition. No correlation was noted between the total serum IgE level (and thus the number of IgE receptors on the basophil surface) and the magnitude of D/sub 2/O release. No increase in D/sub 2/O release was observed in 17 ragweed-sensitive patients through a ragweed season. A unique property of D/sub 2/O release was the loss of reactivity by preincubating cells at 37/sup 0/C for 30 min before adding D/sub 2/O. Non-D/sub 2/O-reactive cells could be ''converted'' to D/sub 2/O-reactive cells by incubation with antigen in the whole blood phase during leukocyte isolation; these cells showed the same loss of releaseability at 37/sup 0/C and an inhibitor profile similar to D/sub 2/O-responsive cells from ragweed allergic or asthmatic patients. We suggest that D/sub 2/O-based buffers reveal, in atopic and asthmatic patients, in vivo basophil activation; whether this is due to IgE cross-links, to C split products, or to other stimuli is not yet clear.

  8. Enhancing the Identification of Phosphopeptides from Putative Basophilic Kinase Substrates Using Ti (IV) Based IMAC Enrichment*

    PubMed Central

    Zhou, Houjiang; Low, Teck Y.; Hennrich, Marco L.; van der Toorn, Henk; Schwend, Thomas; Zou, Hanfa; Mohammed, Shabaz; Heck, Albert J. R.

    2011-01-01

    Metal and metal oxide chelating-based phosphopeptide enrichment technologies provide powerful tools for the in-depth profiling of phosphoproteomes. One weakness inherent to current enrichment strategies is poor binding of phosphopeptides containing multiple basic residues. The problem is exacerbated when strong cation exchange (SCX) is used for pre-fractionation, as under low pH SCX conditions phosphorylated peptides with multiple basic residues elute with the bulk of the tryptic digest and therefore require more stringent enrichment. Here, we report a systematic evaluation of the characteristics of a novel phosphopeptide enrichment approach based on a combination of low pH SCX and Ti4+-immobilized metal ion affinity chromatography (IMAC) comparing it one-to-one with the well established low pH SCX-TiO2 enrichment method. We also examined the effect of 1,1,1,3,3,3-hexafluoroisopropanol (HFP), trifluoroacetic acid (TFA), or 2,5-dihydroxybenzoic acid (DHB) in the loading buffer, as it has been hypothesized that high levels of TFA and the perfluorinated solvent HFP improve the enrichment of phosphopeptides containing multiple basic residues. We found that Ti4+-IMAC in combination with TFA in the loading buffer, outperformed all other methods tested, enabling the identification of around 5000 unique phosphopeptides containing multiple basic residues from 400 μg of a HeLa cell lysate digest. In comparison, ∼2000 unique phosphopeptides could be identified by Ti4+-IMAC with HFP and close to 3000 by TiO2. We confirmed, by motif analysis, the basic phosphopeptides enrich the number of putative basophilic kinases substrates. In addition, we performed an experiment using the SCX/Ti4+-IMAC methodology alongside the use of collision-induced dissociation (CID), higher energy collision induced dissociation (HCD) and electron transfer dissociation with supplementary activation (ETD) on considerably more complex sample, consisting of a total of 400 μg of triple dimethyl labeled

  9. Diclofenac induces basophil degranulation without increasing CD63 expression in sensitive patients

    PubMed Central

    Malbrán, A; Yeyati, E; Rey, G L; Galassi, N

    2007-01-01

    Diclofenac (Dc) induces an IgE-independent basophil (Ba) degranulation in susceptible individuals. CD63 Ba expression is utilized as an in vitro test for diagnosis of drug hypersensitivity. We tested the ability of Dc to induce CD63 Ba expression by flow cytometry (BAT) and Ba degranulation using light microscopy (HBDT) in patients sensitive to Dc. We studied 14 patients with diclofenac hypersensitivity, also two patients sensitive to Dermatophagoides pteronyssinus (Dp), and 12 normal controls. HBDT was performed by mononuclear cells toluidine blue staining. BAT determined CD63 expression in antiCD63/anti-IgE/anti-CD45-labelled whole blood. In each case, the percentage of activated Ba post-stimulation with 1 and 10 µg/ml Dc was determined. Positive controls included N-formyl-methionyl-leucyl-phenylalanine (fMLP) peptide-induced activation. IgE-mediated Ba activation was induced with a Dp allergenic extract. With Dc 1 µg/ml, mean HBDT in Dc-susceptible individuals was 33·62 ± 18·35% and 8·49 ± 4·79% in controls (P = 0·0001). Mean BAT was 2·04 ± 1·68% and 1·93 ± 1·40% in controls (P = 0·8). Ba preincubation with Dc did not affect fMLP-induced CD63 expression, neither in Dc-sensitive individuals (P = 0·8) (n = 4) nor in subjects without Dc hypersensitivity (P = 0·25) (n = 4). Ba from the two patients sensitive both to Dc and Dp responded to Dp but not to Dc by BAT: Dc, 1·99 ± 0·78%; Dp: 60·87 ± 9·28%; but showed degranulation by HBDT: Dc, 30·53 ± 1·02%, Dp: 48·78 ± 22·17%. Dc induces Ba degranulation in sensitive patients in a way that does not induce CD63 expression and is different from IgE-mediated and fMLP-mediated degranulation. Our results suggest that CD63 expression is not a reliable diagnostic method for diclofenac allergy. PMID:17177968

  10. LEUKEMIA-ASSOCIATED TRANSPLANTATION ANTIGENS RELATED TO MURINE LEUKEMIA VIRUS

    PubMed Central

    Sato, H.; Boyse, E. A.; Aoki, T.; Iritani, C.; Old, L. J.

    1973-01-01

    Two BALB radiation leukemias are strongly rejected by hybrids of BALB with certain other mouse strains, although BALB mice themselves exhibit no detectable resistance whatever. Hybrids immunized with progressively increased inocula are resistant to 200 x 106 or more leukemia cells; their serum is cytotoxic for the leukemia cells in vitro and protects BALB mice against challenge with these BALB leukemias. The antigenic system thus identified has been named X.1. In (BALB x B6) hybrids the major determinant of resistance was shown to be a B6 gene in the K region of H-2. This is likely to be the Rgv-1 (Resistance to gross virus) locus of Lilly, which may thus be identified in this case as an Ir (Immune response) allele conferring ability to respond to X.1 antigen on MuLV and leukemia cells, and so responsible for production of X.1 antibody and the rejection of X.1+ leukemia cells by hybrid mice. Immunoelectron microscopy with X.1 antiserum (from immunized hybrids) shows labeling both on the cell surface and on virions produced by the leukemia cells. It is not known whether X.1 comprises only one or more than one antigen. Three radiation-induced BALB leukemias, one A strain radiation-induced leukemia, and 15/15 AKR primary spontaneous leukemias were typed X.1+ by the cytotoxicity test. Several other leukemias, including one induced by passage A Gross virus and one long-transplanted AKR ascites leukemia carried in (B6 x AKR)F1 hybrids, were X.1-. Normal mice of strains with a high incidence of leukemia and one other strain (129) express X.1 antigen, but evidently in amounts too small for certain detection in vitro; by the method of absorption in vivo, however, these strains could be typed X.1+ and other strains X.1-. We ascribe the X.1 antigen system tentatively to a sub-type of MuLV that is not passage A Gross virus and is probably not the dominant sub-type in strains with a high incidence of leukemia. After repeated passage in hybrids, one of the BALB leukemias became

  11. Leukemia and Benzene

    PubMed Central

    Snyder, Robert

    2012-01-01

    Excessive exposure to benzene has been known for more than a century to damage the bone marrow resulting in decreases in the numbers of circulating blood cells, and ultimately, aplastic anemia. Of more recent vintage has been the appreciation that an alternative outcome of benzene exposure has been the development of one or more types of leukemia. While many investigators agree that the array of toxic metabolites, generated in the liver or in the bone marrow, can lead to traumatic bone marrow injury, the more subtle mechanisms leading to leukemia have yet to be critically dissected. This problem appears to have more general interest because of the recognition that so-called “second cancer” that results from prior treatment with alkylating agents to yield tumor remissions, often results in a type of leukemia reminiscent of benzene-induced leukemia. Furthermore, there is a growing literature attempting to characterize the fine structure of the marrow and the identification of so called “niches” that house a variety of stem cells and other types of cells. Some of these “niches” may harbor cells capable of initiating leukemias. The control of stem cell differentiation and proliferation via both inter- and intra-cellular signaling will ultimately determine the fate of these transformed stem cells. The ability of these cells to avoid checkpoints that would prevent them from contributing to the leukemogenic response is an additional area for study. Much of the study of benzene-induced bone marrow damage has concentrated on determining which of the benzene metabolites lead to leukemogenesis. The emphasis now should be directed to understanding how benzene metabolites alter bone marrow cell biology. PMID:23066403

  12. What Are the Key Statistics about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Leukemia (ALL) What Are the Key Statistics About Acute Lymphocytic Leukemia? The American Cancer Society’s estimates for acute lymphocytic ... Acute Lymphocytic Leukemia Research and Treatment? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  13. Do We Know What Causes Chronic Myelomonocytic Leukemia?

    MedlinePlus

    ... Prevention Do We Know What Causes Chronic Myelomonocytic Leukemia? Some cases of chronic myelomonocytic leukemia (CMML) are ... Myelomonocytic Leukemia Be Prevented? More In Chronic Myelomonocytic Leukemia About Chronic Myelomonocytic Leukemia Causes, Risk Factors, and ...

  14. Clinical safety of Food Allergy Herbal Formula-2 (FAHF-2) and inhibitory effect on basophils from patients with food allergy: Extended phase I study.

    PubMed

    Patil, Sangita P; Wang, Julie; Song, Ying; Noone, Sally; Yang, Nan; Wallenstein, Sylvan; Sampson, Hugh A; Li, Xiu-Min

    2011-12-01

    Food allergy is a common and increasing health concern in westernized countries. No effective treatment is available, and accidental ingestion can be life-threatening. Food Allergy Herbal Formula-2 (FAHF-2) blocks peanut-induced anaphylaxis in a murine model of peanut-induced anaphylaxis. It was found to be safe and well tolerated in an acute phase I study of patients with food allergy. We sought to assess the safety of FAHF-2 in an extended phase I clinical trial and determine the potential effects on peripheral blood basophils from patients with food allergy. Patients in an open-label study received 3.3 g (6 tablets) of FAHF-2 three times a day for 6 months. Vital signs, physical examination results, laboratory data, pulmonary function test results, and electrocardiographic data were acquired at baseline and at 2-month intervals. During the course of the study, basophil activation and basophil and eosinophil numbers were evaluated by using CCR3/CD63 staining and flow cytometry. Of 18 patients enrolled, 14 completed the study. No significant drug-associated differences in laboratory parameters, pulmonary function study results, or electrocardiographic findings before and after treatment were found. There was a significant reduction (P < .010) in basophil CD63 expression in response to ex vivo stimulation at month 6. There was also a trend toward a reduction in eosinophil and basophil numbers after treatment. FAHF-2 was safe and well tolerated and had an inhibitory effects on basophil numbers in an extended phase I clinical study. A controlled phase II study is warranted. Copyright © 2011 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.

  15. Acid hydrolysis of wheat gluten induces formation of new epitopes but does not enhance sensitizing capacity by the oral route: a study in "gluten free" Brown Norway rats.

    PubMed

    Kroghsbo, Stine; Andersen, Nanna B; Rasmussen, Tina F; Jacobsen, Susanne; Madsen, Charlotte B

    2014-01-01

    Acid hydrolyzed wheat proteins (HWPs) are used in the food and cosmetic industry as emulsifiers. Cases of severe food allergic reactions caused by HWPs have been reported. Recent data suggest that these reactions are caused by HWPs produced by acid hydrolysis. To examine the sensitizing capacity of gluten proteins per se when altered by acid or enzymatic hydrolysis relative to unmodified gluten in rats naïve to gluten. High IgE-responder Brown Norway (BN) rats bred on a gluten-free diet were sensitized without the use of adjuvant to three different gluten products (unmodified, acid hydrolyzed and enzymatic hydrolyzed). Rats were sensitized by intraperitoneal (i.p.) immunization three times with 200 µg gluten protein/rat or by oral dosing for 35 days with 0.2, 2 or 20 mg gluten protein/rat/day. Sera were analyzed for specific IgG and IgE and IgG-binding capacity by ELISA. IgE functionality was measured by rat basophilic leukemia (RBL) assay. Regardless of the route of dosing, all products had sensitizing capacity. When sensitized i.p., all three gluten products induced a strong IgG1 response in all animals. Acid hydrolyzed gluten induced the highest level of specific IgE but with a low functionality. Orally all three gluten products induced specific IgG1 and IgE but with different dose-response relations. Sensitizing rats i.p. or orally with unmodified or enzymatic hydrolyzed gluten induced specific IgG1 responses with similar binding capacity which was different from that of acid hydrolyzed gluten indicating that acid hydrolysis of gluten proteins induces formation of 'new' epitopes. In rats not tolerant to gluten acid hydrolysis of gluten enhances the sensitizing capacity by the i.p. but not by the oral route. In addition, acid hydrolysis induces formation of new epitopes. This is in contrast to the enzymatic hydrolyzed gluten having an epitope pattern similar to unmodified gluten.

  16. Monosodium urate crystals induce extracellular DNA traps in neutrophils, eosinophils, and basophils but not in mononuclear cells.

    PubMed

    Schorn, Christine; Janko, Christina; Latzko, Melanie; Chaurio, Ricardo; Schett, Georg; Herrmann, Martin

    2012-01-01

    Neutrophil extracellular traps (NETs) are fibers of extracellular DNA released from neutrophils due to overwhelming phagocytic stimuli. The function of NETs is to trap and kill microbes to avoid spreading of potential pathogens. NETs are formed after encounter with various gram-positive and -negative bacteria but also in response to mediators causing sterile inflammation like interleukin-8 (IL-8), tumor necrosis factor (TNF), and phorbol myristate acetate (PMA). Here we show the formation of NETs (NETting) in response to monosodium urate (MSU) crystals as further model for sterile inflammation. We identified monocytes, neutrophils, and eosinophils as MSU phagocytosing cells. Basophils did not take up the crystals, instead they upregulated their activation marker CD203c after contact with MSU. Nevertheless, MSU crystals induced extracellular trap formation also in basophils, like in eosinophils and neutrophils, which phagocytose the crystals. In contrast, monocytes do not form NETs despite uptake of the MSU crystals. In contrast to the canonical stimuli like bacteria and PMA, MSU-induced NETosis was not abrogated by plasma. Our data show that MSU crystals induce extracellular DNA trap formation in all three granulocytes lineages (NETs, EETs, and BETs) but not in monocytes, and DNA externalization does not necessitate the uptake of the crystals.

  17. Immunoglobulin D enhances immune surveillance by activating antimicrobial, proinflammatory and B cell-stimulating programs in basophils.

    PubMed

    Chen, Kang; Xu, Weifeng; Wilson, Melanie; He, Bing; Miller, Norman W; Bengtén, Eva; Edholm, Eva-Stina; Santini, Paul A; Rath, Poonam; Chiu, April; Cattalini, Marco; Litzman, Jiri; B Bussel, James; Huang, Bihui; Meini, Antonella; Riesbeck, Kristian; Cunningham-Rundles, Charlotte; Plebani, Alessandro; Cerutti, Andrea

    2009-08-01

    Immunoglobulin D (IgD) is an enigmatic antibody isotype that mature B cells express together with IgM through alternative RNA splicing. Here we report active T cell-dependent and T cell-independent IgM-to-IgD class switching in B cells of the human upper respiratory mucosa. This process required activation-induced cytidine deaminase (AID) and generated local and circulating IgD-producing plasmablasts reactive to respiratory bacteria. Circulating IgD bound to basophils through a calcium-mobilizing receptor that induced antimicrobial, opsonizing, inflammatory and B cell-stimulating factors, including cathelicidin, interleukin 1 (IL-1), IL-4 and B cell-activating factor (BAFF), after IgD crosslinking. By showing dysregulation of IgD class-switched B cells and 'IgD-armed' basophils in autoinflammatory syndromes with periodic fever, our data indicate that IgD orchestrates an ancestral surveillance system at the interface between immunity and inflammation.

  18. [Anaphylactic shock due to recombinant human insulin: follow-up of a desensitization protocol by basophil activation test].

    PubMed

    Luyasu, S; Hougardy, N; Hasdenteufel, F; Jacquenet, S; Weber, E; Moneret-Vautrin, A; Kanny, G

    2011-01-01

    Despite the occurrence of a severe allergic reaction including an anaphylactic shock, a drug may remain essential and impossible to replace. This may be the case of insulin in a diabetic patient. We describe the case of an anaphylactic shock to human insulin in whom a desensitization protocol was successfully achieved. A 50-year-old type 2 diabetic man presented one year after initiation of the insulin therapy an anaphylactic shock following the subcutaneous administration of a human insulin containing protamine (Insulatard®). A desensitization protocol to human insulin was performed and allowed to use two human insulin analogues containing no protamine (asparte and glargine), with a two-year event-free follow-up. Positive skin tests with insulin and protamine, and the presence of insulin specific IgE were evidenced of an IgE-mediated mechanism. Desensitization was monitored by skin tests, Maunsell's test, measurement of specific IgE and IgG4, and the basophil activation test. The decrease of basophil sensitivity to insulin is an early marker for tolerance induction. The effectiveness of the desensitization to human insulin underlines the importance to define the modalities of such desensitization protocol and of the monitoring of the tolerance induction. Copyright © 2010 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  19. Genetics Home Reference: chronic myeloid leukemia

    MedlinePlus

    ... Home Health Conditions chronic myeloid leukemia chronic myeloid leukemia Printable PDF Open All Close All Enable Javascript ... view the expand/collapse boxes. Description Chronic myeloid leukemia is a slow-growing cancer of the blood- ...

  20. Treating Chronic Myeloid Leukemia by Phase

    MedlinePlus

    ... Myeloid Leukemia Targeted Therapies for Chronic Myeloid Leukemia Interferon Therapy for Chronic Myeloid Leukemia Chemotherapy for Chronic ... to help decide what drug would be best. Interferon or chemotherapy (chemo) may be tried for those ...

  1. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    ClinicalTrials.gov

    2017-02-20

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  2. MS-275 and Azacitidine in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-01-31

    Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  3. Phase I Dose-Escalation Trial of Clofarabine Followed by Escalating Doses of Fractionated Cyclophosphamide in Children With Relapsed or Refractory Acute Leukemias

    ClinicalTrials.gov

    2010-09-21

    Myelodysplastic Syndrome; Acute Myeloid Leukemia; Myeloproliferative Disorders; Acute Lymphocytic Leukemia; Acute Promyelocytic Leukemia; Acute Leukemia; Chronic Myelogenous Leukemia; Myelofibrosis; Chronic Myelomonocytic Leukemia; Juvenile Myelomonocytic Leukemia

  4. Temsirolimus and Imatinib Mesylate in Treating Patients With Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-11

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Relapsing Chronic Myelogenous Leukemia

  5. Imatinib Mesylate and Decitabine in Treating Patients With Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-22

    Accelerated Phase Chronic Myelogenous Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Relapsing Chronic Myelogenous Leukemia

  6. Donor cell leukemia.

    PubMed

    Ruiz-Arguelles, Alejandro

    2012-04-01

    Minimal residual disease refers to the tumour cells that are still present in a given patient after completion of a therapeutic scheme. The demonstration and quantification of residual neoplastic cells has a crucial impact in clinical decision making, for it might prompt continuation of treatment, while the absence of such cells might serve as evidence to withdraw therapy. Therefore, both sensitivity and specificity of the methods used to unravel residual neoplastic cells must be highly reliable and robust. Flow cytometry has been widely used for this purpose, and its clinical performance depends mainly on the criteria of interpretation, rather than in the technique by itself; molecular biology techniques have proved to be highly sensitive and specific but unfortunately they cannot be used in all patients or in all types of leukemia. Finally, the development of donor cell leukemia in transplanted patients, might mimic residual disease and add more confusion to an already controversial issue. These topics are discussed in this paper.

  7. Mast cell leukemia.

    PubMed

    Georgin-Lavialle, Sophie; Lhermitte, Ludovic; Dubreuil, Patrice; Chandesris, Marie-Olivia; Hermine, Olivier; Damaj, Gandhi

    2013-02-21

    Mast cell leukemia (MCL) is a very rare form of aggressive systemic mastocytosis accounting for < 1% of all mastocytosis. It may appear de novo or secondary to previous mastocytosis and shares more clinicopathologic aspects with systemic mastocytosis than with acute myeloid leukemia. Symptoms of mast cell activation-involvement of the liver, spleen, peritoneum, bones, and marrow-are frequent. Diagnosis is based on the presence of ≥ 20% atypical mast cells in the marrow or ≥ 10% in the blood; however, an aleukemic variant is frequently encountered in which the number of circulating mast cells is < 10%. The common phenotypic features of pathologic mast cells encountered in most forms of mastocytosis are unreliable in MCL. Unexpectedly, non-KIT D816V mutations are frequent and therefore, complete gene sequencing is necessary. Therapy usually fails and the median survival time is < 6 months. The role of combination therapies and bone marrow transplantation needs further investigation.

  8. IMMUNOTHERAPY IN ACUTE LEUKEMIA

    PubMed Central

    Leung, Wing

    2010-01-01

    Recent advances in immunotherapy of cancer may represent a successful example in translational research, in which progress in knowledge and technology in immunology has lead to new strategies of immunotherapy, and even past failure in many clinical trials have led to a better understanding of basic cancer immunobiology. This article reviews the latest concepts in antitumor immunology and its application in the treatment of cancer, with particular focus on acute leukemia. PMID:19100371

  9. Phase 1 Study of Terameprocol (EM-1421) in Patients With Leukemia

    ClinicalTrials.gov

    2016-02-20

    Leukemias; Acute Myeloid Leukemia (AML); Acute Lymphocytic Leukemia (ALL); Adult T Cell Leukemia (ATL); Chronic Myeloid Leukemia (CML-BP); Chronic Lymphocytic Leukemia (CLL); Myelodysplastic Syndrome (MDS); Chronic Myelomonocytic Leukemia (CMML)

  10. SB-715992 in Treating Patients With Acute Leukemia, Chronic Myelogenous Leukemia, or Advanced Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-01-10

    Acute Undifferentiated Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  11. Childhood Leukemia and Primary Prevention

    PubMed Central

    Whitehead, Todd P.; Metayer, Catherine; Wiemels, Joseph L.; Singer, Amanda W.; Miller, Mark D.

    2016-01-01

    Leukemia is the most common pediatric cancer, affecting 3,800 children per year in the United States. Its annual incidence has increased over the last decades, especially among Latinos. Although most children diagnosed with leukemia are now cured, many suffer long-term complications, and primary prevention efforts are urgently needed. The early onset of leukemia – usually before age five – and the presence at birth of “pre-leukemic” genetic signatures indicate that pre- and postnatal events are critical to the development of the disease. In contrast to most pediatric cancers, there is a growing body of literature – in the United States and internationally – that has implicated several environmental, infectious, and dietary risk factors in the etiology of childhood leukemia, mainly for acute lymphoblastic leukemia, the most common subtype. For example, exposures to pesticides, tobacco smoke, solvents, and traffic emissions have consistently demonstrated positive associations with the risk of developing childhood leukemia. In contrast, intake of vitamins and folate supplementation during the pre-conception period or pregnancy, breastfeeding, and exposure to routine childhood infections have been shown to reduce the risk of childhood leukemia. Some children may be especially vulnerable to these risk factors, as demonstrated by a disproportionate burden of childhood leukemia in the Latino population of California. The evidence supporting the associations between childhood leukemia and its risk factors – including pooled analyses from around the world and systematic reviews – is strong; however, the dissemination of this knowledge to clinicians has been limited. To protect children’s health, it is prudent to initiate programs designed to alter exposure to well-established leukemia risk factors rather than to suspend judgement until no uncertainty remains. Primary prevention programs for childhood leukemia would also result in the significant co

  12. A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/α-1) Mediates IgE Binding for Antigen-independent Basophil Activation*

    PubMed Central

    Meyer, N. Helge; Mayerhofer, Hubert; Tripsianes, Konstantinos; Blindow, Silke; Barths, Daniela; Mewes, Astrid; Weimar, Thomas; Köhli, Thies; Bade, Steffen; Madl, Tobias; Frey, Andreas; Haas, Helmut; Mueller-Dieckmann, Jochen; Sattler, Michael; Schramm, Gabriele

    2015-01-01

    The IL-4-inducing principle from Schistosoma mansoni eggs (IPSE/α-1), the major secretory product of eggs from the parasitic worm S. mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/α-1 requires the presence of IgE on the basophils, but the detailed molecular mechanism underlying activation is unknown. NMR and crystallographic analysis of IPSEΔNLS, a monomeric IPSE/α-1 mutant, revealed that IPSE/α-1 is a new member of the βγ-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSEΔNLS with the 180-kDa molecule IgE identified a large positively charged binding surface that includes a flexible loop, which is unique to the IPSE/α-1 crystallin fold. Mutational analysis of amino acids in the binding interface showed that residues contributing to IgE binding are important for IgE-dependent activation of basophils. As IPSE/α-1 is unable to cross-link IgE, we propose that this molecule, by taking advantage of its unique IgE-binding crystallin fold, activates basophils by a novel, cross-linking-independent mechanism. PMID:26163514

  13. A Crystallin Fold in the Interleukin-4-inducing Principle of Schistosoma mansoni Eggs (IPSE/α-1) Mediates IgE Binding for Antigen-independent Basophil Activation.

    PubMed

    Meyer, N Helge; Mayerhofer, Hubert; Tripsianes, Konstantinos; Blindow, Silke; Barths, Daniela; Mewes, Astrid; Weimar, Thomas; Köhli, Thies; Bade, Steffen; Madl, Tobias; Frey, Andreas; Haas, Helmut; Mueller-Dieckmann, Jochen; Sattler, Michael; Schramm, Gabriele

    2015-09-04

    The IL-4-inducing principle from Schistosoma mansoni eggs (IPSE/α-1), the major secretory product of eggs from the parasitic worm S. mansoni, efficiently triggers basophils to release the immunomodulatory key cytokine interleukin-4. Activation by IPSE/α-1 requires the presence of IgE on the basophils, but the detailed molecular mechanism underlying activation is unknown. NMR and crystallographic analysis of IPSEΔNLS, a monomeric IPSE/α-1 mutant, revealed that IPSE/α-1 is a new member of the βγ-crystallin superfamily. We demonstrate that this molecule is a general immunoglobulin-binding factor with highest affinity for IgE. NMR binding studies of IPSEΔNLS with the 180-kDa molecule IgE identified a large positively charged binding surface that includes a flexible loop, which is unique to the IPSE/α-1 crystallin fold. Mutational analysis of amino acids in the binding interface showed that residues contributing to IgE binding are important for IgE-dependent activation of basophils. As IPSE/α-1 is unable to cross-link IgE, we propose that this molecule, by taking advantage of its unique IgE-binding crystallin fold, activates basophils by a novel, cross-linking-independent mechanism.

  14. Sinomenine potentiates degranulation of RBL-2H3 basophils via up-regulation of phospholipase A2 phosphorylation by Annexin A1 cleavage and ERK phosphorylation without influencing on calcium mobilization.

    PubMed

    Huang, Lufen; Li, Ting; Zhou, Hua; Qiu, Ping; Wu, Jianlin; Liu, Liang

    2015-10-01

    Sinomenine (SIN), an alkaloid derived from the Chinese medicinal plant Sinomenium acutum, is the major component of Zhengqing Fongtong Ning (ZQFTN), a pharmaceutical drug produced by Hunan Zhengqing Pharmaceutical Co. Ltd. in China for the treatment of rheumatoid arthritis and other autoimmune diseases. Some clinic reports indicate that ZQFTN may induce an anaphylactic reaction via potentiating the degranulation of immune cells. In the current study, we aimed to examine whether SIN is capable of inducing the degranulation of basophilic leukemia 2H3 (RBL-2H3) cells to elucidate how the anaphylactic reaction occurs. The results revealed that SIN could up-regulate β-hexosaminidase levels in RBL-2H3 cells without significant cytotoxicity, suggesting that SIN could induce the degranulation of RBL-2H3 cells. Furthermore, SIN increased the release of prostaglandin D2 (PGD2) and prostaglandin E2 (PGE2) in RBL-2H3 cells via promoting the expression of phosphorylated-extracellular signal-regulated kinase (P-ERK), the cleavage of Annexin A1 (ANXA1), and phosphorylated-cytosolic phospholipase A2 (P-cPLA2), as well as cyclooxygenase-2 (COX-2). The ERK inhibitor, PD98059, significantly attenuated the up-regulatory effect of SIN on cPLA2 phosphorylation. Interestingly, SIN did not significantly increase Ca(2+) influx in the cells. These findings not only explored the anaphylactic reaction and underlying mechanism of ZQFTN in RBL-2H3 cells, but may promote the development of relevant strategies for overcoming the adverse effects of the drug.

  15. Developmental Outcome of Childhood Leukemia.

    ERIC Educational Resources Information Center

    Coniglio, Susan J.; Blackman, James A.

    1995-01-01

    Literature on developmental and psychosocial outcomes of childhood leukemia is reviewed, focusing on preschool-age children. Studies are categorized in terms of outcome measures: intelligence/achievement, neuropsychological, memory/attention, and psychosocial tests. Evidence suggests that preschool children with leukemia are at high risk for…

  16. Developmental Outcome of Childhood Leukemia.

    ERIC Educational Resources Information Center

    Coniglio, Susan J.; Blackman, James A.

    1995-01-01

    Literature on developmental and psychosocial outcomes of childhood leukemia is reviewed, focusing on preschool-age children. Studies are categorized in terms of outcome measures: intelligence/achievement, neuropsychological, memory/attention, and psychosocial tests. Evidence suggests that preschool children with leukemia are at high risk for…

  17. Obinutuzumab in chronic lymphocytic leukemia.

    PubMed

    Dupuis, Jehan

    2015-09-01

    Obinutuzumab is the second next-generation monoclonal anti-CD20 antibody (after ofatumumab) to enter clinical practice in chronic lymphocytic leukemia. Its superiority in association with chlorambucil as compared with chlorambucil alone has led to its approval as a first-line treatment for chronic lymphocytic leukemia, for patients who are not candidates for a more intensive treatment.

  18. Basophilic round bodies in gastric biopsies little known by pathologists: iatrogenic yttrium 90 microspheres deriving from selective internal radiation therapy.

    PubMed

    Luo, Dong-Lan; Chan, John K C

    2013-10-01

    Selective internal radiation therapy is a relatively new technique that irradiates primary and metastatic liver cancer using yttrium 90 microspheres. Increasing reports have shown this to be a useful treatment for unresectable primary hepatocellular carcinoma and others metastases from colon, lung, breast, sarcoma, and ocular melanoma. On the other hand, more and more therapy-related complications have been described. Since the morphologic description of injured organs are relatively uncommon, we report 2 cases of selective internal radiation therapy-related gastric injury, which represent basophilic round bodies in gastric biopsies little known by pathologists. The appearances in esophagogastroduodenoscopy include gastrointestinal ulcer, edema, and bleeding. Histological findings are mucosal atrophy, mild to moderate cytologic atypia, edema of the stroma, and inflammatory infiltration. The most characteristic feature is the presence of round blue and dark microspheres in the stromal blood vessels.

  19. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2017-07-14

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  20. Down-Regulation of FcεRI-Mediated CD63 Basophil Response during Short-Term VIT Determined Venom-Nonspecific Desensitization

    PubMed Central

    Čelesnik Smodiš, Nina; Šilar, Mira; Eržen, Renato; Rijavec, Matija; Košnik, Mitja; Korošec, Peter

    2014-01-01

    Background We recently showed a desensitization of FcεRI-mediated basophil response after short-term VIT. Our aim was to evaluate the allergen specificity of this desensitization. Methods In 11 Hymenoptera-venom double positive subjects, basophil threshold sensitivity (CD-sens) to anti-FcεRI, honeybee, and Vespula venom was assessed at the beginning and just before the first maintenance dose (MD) of single ultra-rush VIT. In some patients we also monitored CD-sens to rApi m 1 and/or rVes v 5 or other co-sensitizations (i.e., grass pollen). In additional 7 patients, basophils were stripped and sensitized with house dust mite (HDM) IgEs at the same time points. Results We demonstrated a marked reduction of CD-sens to anti-FcεRI and VIT-specific venom before the first MD in all 18 subjects included. Furthermore, in 10 out of 11 double positive subjects, a significant and comparable decrease before the first MD was also evident for non-VIT venom; this nonspecific decrease was further supported by the opposite recombinant species-specific major allergen. In one subject with additional grass pollen allergy, a decrease of CD-sens to grass allergen was also demonstrated. Similarly, in 7 cases of patients with passively HDM-sensitized basophils, a significant reduction of CD-sens was also evident to de novo sensitized HDM allergen. Conclusions Short-term VIT induced basophil desensitization to VIT-specific as well as to VIT-nonspecific venom. As opposed to long-term VIT, which induces venom-specific changes, the effect of short-term VIT seems to be venom-nonspecific. PMID:24733549

  1. The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) is a potent inhibitor of mediator release from human dermal mast cells and peripheral blood basophils.

    PubMed

    Zuberbier, T; Chong, S U; Grunow, K; Guhl, S; Welker, P; Grassberger, M; Henz, B M

    2001-08-01

    The ascomycin macrolactam pimecrolimus (Elidel, SDZ ASM 981) has recently been developed as a novel and cell-selective inhibitor of inflammatory cytokine secretion; it has fewer adverse effects than currently available drugs. In this study, we investigated the capacity of pimecrolimus to directly inhibit in vitro mediator release from human skin mast cells and basophils. Purified cutaneous mast cells or basophil-containing peripheral blood leukocytes were obtained from healthy human donors and preincubated with pimecrolimus (0.1 nmol/L to 1 micromol/L) in the absence or presence of its specific antagonist (rapamycin), cyclosporin A (100 nmol/L to 1 micromol/L), or dexamethasone (1 micromol/L) and then stimulated with anti-IgE or with calcium ionophore A23187 plus phorbol myristate acetate. Cell supernatants were kept for analysis of histamine, tryptase, LTC4, and TNF-alpha. Pimecrolimus caused a strong and dose-dependent inhibition of anti-IgE--induced release of histamine from mast cells and basophils (maximally 73% and 82%, respectively, at 500 nmol/L pimecrolimus) and of mast cell tryptase (maximally 75%) and a less pronounced inhibition of LTC4 (maximally 32%) and of calcium ionophore plus phorbol myristate acetate--induced mast cell TNF-alpha release (90% maximum at 100 nmol/L pimecrolimus). In contrast, inhibition achieved during mast cell histamine release was maximally 60% with cyclosporin A and only 28% with dexamethasone. These data demonstrate a marked inhibitory capacity of pimecrolimus on mediator release from human mast cells and basophils with a potency exceeding that of cyclosporin A and dexamethasone. Pimecrolimus might thus be expected to be effective in the treatment of mast cell-- and basophil-dependent diseases.

  2. Acid Hydrolysis of Wheat Gluten Induces Formation of New Epitopes but Does Not Enhance Sensitizing Capacity by the Oral Route: A Study in “Gluten Free” Brown Norway Rats

    PubMed Central

    Kroghsbo, Stine; Andersen, Nanna B.; Rasmussen, Tina F.; Madsen, Charlotte B.

    2014-01-01

    Background Acid hydrolyzed wheat proteins (HWPs) are used in the food and cosmetic industry as emulsifiers. Cases of severe food allergic reactions caused by HWPs have been reported. Recent data suggest that these reactions are caused by HWPs produced by acid hydrolysis. Objectives To examine the sensitizing capacity of gluten proteins per se when altered by acid or enzymatic hydrolysis relative to unmodified gluten in rats naïve to gluten. Methods High IgE-responder Brown Norway (BN) rats bred on a gluten-free diet were sensitized without the use of adjuvant to three different gluten products (unmodified, acid hydrolyzed and enzymatic hydrolyzed). Rats were sensitized by intraperitoneal (i.p.) immunization three times with 200 µg gluten protein/rat or by oral dosing for 35 days with 0.2, 2 or 20 mg gluten protein/rat/day. Sera were analyzed for specific IgG and IgE and IgG-binding capacity by ELISA. IgE functionality was measured by rat basophilic leukemia (RBL) assay. Results Regardless of the route of dosing, all products had sensitizing capacity. When sensitized i.p., all three gluten products induced a strong IgG1 response in all animals. Acid hydrolyzed gluten induced the highest level of specific IgE but with a low functionality. Orally all three gluten products induced specific IgG1 and IgE but with different dose-response relations. Sensitizing rats i.p. or orally with unmodified or enzymatic hydrolyzed gluten induced specific IgG1 responses with similar binding capacity which was different from that of acid hydrolyzed gluten indicating that acid hydrolysis of gluten proteins induces formation of ‘new’ epitopes. Conclusions In rats not tolerant to gluten acid hydrolysis of gluten enhances the sensitizing capacity by the i.p. but not by the oral route. In addition, acid hydrolysis induces formation of new epitopes. This is in contrast to the enzymatic hydrolyzed gluten having an epitope pattern similar to unmodified gluten. PMID:25207551

  3. Chronic neutrophilic leukemia with congenital Robertsonian translocation successfully treated with allogeneic bone marrow transplantation in a young man.

    PubMed

    Goto, Hideko; Hara, Takeshi; Tsurumi, Hisashi; Tanabashi, Shinobu; Moriwaki, Hisataka

    2009-01-01

    We present a 23-year-old man with chronic neutrophilic leukemia (CNL). Physical examination revealed hepatosplenomegaly. Leukocytosis was evident with predominance of mature neutrophils with basophilic granules. Bone marrow aspiration revealed mature myeloid hyperplasia. Congenital Robertsonian translocation [45,XY,der(13;22)(q10;q10), in all of analyzed 20 cells] was detected; however, cytogenetic and molecular studies for 9:22 translocation were negative. He was diagnosed with CNL and hydroxyurea was started to control his symptoms and white blood cell count. He was then successfully treated with allogeneic bone marrow transplantation (BMT). Although the prognosis of CNL was not determined, curative therapy including allogeneic hematopoietic stem cell transplantation should be attempted in young patients with CNL.

  4. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    MedlinePlus

    ... TV, Video Games, and the Internet Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) ... Treatment Coping en español Leucemia linfoblástica aguda About Leukemia Leukemia is a type of cancer that affects ...

  5. Juvenile Myelomonocytic Leukemia (JMML) (For Parents)

    MedlinePlus

    ... TV, Video Games, and the Internet Juvenile Myelomonocytic Leukemia (JMML) KidsHealth > For Parents > Juvenile Myelomonocytic Leukemia (JMML) ... Treatment Coping en español Leucemia mielomonocítica juvenil About Leukemia Leukemia is a type of cancer that affects ...

  6. Chronic Myelogenous Leukemia (CML) (For Parents)

    MedlinePlus

    ... TV, Video Games, and the Internet Chronic Myelogenous Leukemia (CML) KidsHealth > For Parents > Chronic Myelogenous Leukemia (CML) ... Treatment Coping en español Leucemia mielógena crónica About Leukemia Leukemia is a type of cancer that affects ...

  7. Leukemia: Recent advances in biology and treatment

    SciTech Connect

    Gale, R.P.; Golde, D.W.

    1985-01-01

    This book is a compilation of papers presented at a Symposium on the advances in the biology and treatment of leukemia. Topics covered include oncogenes and chromosomes in leukemia - the interactions of oncogenes with hemopoietic cells;the involvement of oncogenes in chronic myelogenous leukemia;oncogene regulation during erythroid differentiation;genomic rearrangements in human cancer;and pathenogenesis of leukemia.

  8. Rebeccamycin Analog in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia, or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  9. SJG-136 in Treating Patients With Relapsed or Refractory Acute Leukemia, Myelodysplastic Syndromes, Blastic Phase Chronic Myelogenous Leukemia, or Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-09-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  10. Roles for the High Affinity IgE Receptor, FcεRI, of Human Basophils in the Pathogenesis and Therapy of Allergic Asthma: Disease Promotion, Protection or Both?

    PubMed

    Youssef, Lama A; Schuyler, Mark; Wilson, Bridget S; Oliver, Janet M

    2010-01-01

    The role of basophils, the rarest of blood granulocytes, in the pathophysiology of allergic asthma is still incompletely understood. Indirect evidence generated over many decades is consistent with a role for basophils in disease promotion. Recent improvements in procedures to purify and analyze very small numbers of human cells have generally supported this view, but have also revealed new complexities. This chapter focuses on our analyses of Fcε R1 function in basophils in the context of understanding and treating human allergic asthma. In long-term studies, we demonstrated that asthmatic subjects have higher circulating numbers of basophils than non-atopic non-asthmatic subjects and that their basophils show higher rates of both basal and anti-IgE or antigen-stimulated histamine release. These results hint at a direct role for basophils in promoting asthma. Supporting this interpretation, the non-releaser phenotype that we linked to the excessive proteolysis of Syk via the ubiquitin/proteasomal pathway is less common in basophils from asthmatic than non-asthmatic donors. The discovery of a basophil-specific pathway regulating Syk levels presents a clear opportunity for therapy. Another route to therapy was revealed by evidence that basophil FcεRI signaling can be downregulated by co-crosslinking the ITAM-containing IgE receptor, FcγRI, to the ITIM-containing IgG receptor, FcγRIIB. Based on this discovery, hybrid co-crosslinking fusion proteins are being engineered as potential therapies targeting basophils. A third distinguishing property of human basophils is their high dependence on IgE binding to stabilize membrane FcεRI. The circulating IgE scavenging mAb, Omalizumab, reduces FcεRI expression in basophils from asthmatics by over 95% and produces a substantial impairment of IL-4, IL-8 and IL-13 production in response to the crosslinking of residual cell surface IgE-FcεRI. A search for small molecule inhibitors that similarly impair high affinity Ig

  11. Bendamustine Plus Alemtuzumab for Refractory Chronic Lymphocytic Leukemia (CLL)

    ClinicalTrials.gov

    2013-08-20

    Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  12. [Molecular targeted therapy in lymphoid leukemias].

    PubMed

    Kojima, Kensuke; Ando, Toshihiko; Kimura, Shinya

    2014-06-01

    Recent advances in the treatment of lymphoid leukemias have incorporated molecular targeted drugs (CD20-targeting rituximab and BCR-ABL tyrosine kinase inhibitors) into the traditional chemotherapeutic agents. This article reviews novel molecular targeted therapies for patients with lymphoid leukemias including acute lymphoblastic leukemia, chronic lymphocytic leukemia, hairly cell leukemia and HTLV-I-related adult T-cell leukemia. Investigational agents that will be discussed in this review include inotuzumab, blinatumomab, alemtuzumab, ofatumumab, ibrutinib, idelalisib, bafetinib, lenalidomide, ABT-199 and mogamulizumab. Novel approaches warrant continued research to improve outcomes for patients with lymphoid leukemias.

  13. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2017-09-14

    Acute Biphenotypic Leukemia; Acute Erythroid Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Megakaryoblastic Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Blasts Under 10 Percent of Bone Marrow Nucleated Cells; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Myelodysplastic Syndrome With Excess Blasts; Pancytopenia; Refractory Anemia; Secondary Acute Myeloid Leukemia

  14. Adult Acute Lymphoblastic Leukemia

    PubMed Central

    Faderl, Stefan; O’Brien, Susan; Pui, Ching-Hon; Stock, Wendy; Wetzler, Meir; Hoelzer, Dieter; Kantarjian, Hagop M.

    2016-01-01

    Acute lymphoblastic leukemia (ALL), a clonal expansion of hematopoietic blasts, is a highly heterogeneous disease comprising many entities for which distinct treatment strategies are pursued. Although ALL is a success story in pediatric oncology, results in adults lag behind those in children. An expansion of new drugs, more reliable immunologic and molecular techniques for the assessment of minimal residual disease, and efforts at more precise risk stratification are generating new aspects of adult ALL therapy. For this review, the authors summarized pertinent and recent literature on ALL biology and therapy, and they discuss current strategies and potential implications of novel approaches to the management of adult ALL. PMID:20101737

  15. Tipifarnib in Treating Patients With Chronic Myeloid Leukemia, Chronic Myelomonocytic Leukemia, or Undifferentiated Myeloproliferative Disorders

    ClinicalTrials.gov

    2017-05-08

    Accelerated Phase of Disease; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Myelomonocytic Leukemia; Chronic Phase of Disease; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Recurrent Disease

  16. Leukemia: genetics and prognostic factors.

    PubMed

    Hamerschlak, Nelson

    2008-08-01

    To present the implications of genetics, particularly of cytogenetic techniques, for the diagnosis and prognosis of leukemia. A survey of articles selected from MEDLINE, American Society of Hematology educational programs, the CAPES web portal, the National Comprehensive Cancer Network and textbook chapters. Since the discovery in 1960 by Peter C. Nowel and David Hungerford of the 9:22 translocation (the Philadelphia chromosome), genetics has come to play an important role in hematology, in this case making it possible to diagnose chronic myeloid leukemia and opening doors to research avenues for the whole field of oncology. One point of great interest refers to the implications of these findings for the prognosis of a range of types of leukemia. In acute myeloid leukemia, the karyotype is of fundamental importance to postremission treatment decisions, and molecular factors determine the treatment of individuals with normal karyotypes. In chronic myeloid leukemia, clonal evolution is associated with progression to the blast crisis. Patients on imatinib who cease responding may have mutations on their ABL gene. Finally, in acute lymphoblastic leukemia, factors such as hyperdiploidy and t 12:21 are associated with good prognosis, whereas carriers of t 4:11 and t 9:22 are considered high risk patients. Genetics has come to stay as far as hematology and, in particular, the management of leukemia and its prognostic factors are concerned. These tests should always be carried out and the appropriate treatment adopted in the light of their results, so that optimal patient outcomes can be achieved.

  17. Entinostat and Clofarabine in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Poor-Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia

    ClinicalTrials.gov

    2014-07-16

    Acute Leukemias of Ambiguous Lineage; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  18. Marrow transplantation for leukemia

    SciTech Connect

    Thomas, E.D.

    1981-07-01

    Marrow transplantation for selected patients with leukemia, as for patients with severe combined immunologic deficiency or severe aplastic anemia, has now become an accepted clinical procedure. For patients with acute leukemia who have relapsed after achieving a remission of chemotherapy, marrow grafting from an identical twin or an HLA-identical sibling has now been demonstrated to produce median remissions as long as or longer than any reported for combination chemotherapy. In contrast to chemotherapy, marrow transplantation offers the possibility of cure for a small but significant fraction of these patients. Marrow transplantation for patients with ANL in first remission has now resulted in median survivals much longer than any reported with chemotherapy. Although it now appears that more than 50% of these patients can be cured with marrow transplantation, a much longer follow-up is indicated since some patients who achieve a complete remission with combination chemotherapy are now living for a long time, and some of these patients (less than 20%) may also be cured. Current intensive research with new modalities such as interferon, Acyclovir, Cyclosporin A, and monoclonal antibodies can reasonably be expected to improve the overall results of marrow transplantation.

  19. MicroRNA profiling can classify acute leukemias of ambiguous lineage as either acute myeloid leukemia or acute lymphoid leukemia.

    PubMed

    de Leeuw, David C; van den Ancker, Willemijn; Denkers, Fedor; de Menezes, Renée X; Westers, Theresia M; Ossenkoppele, Gert J; van de Loosdrecht, Arjan A; Smit, Linda

    2013-04-15

    Classification of acute leukemia is based on the commitment of leukemic cells to the myeloid or the lymphoid lineage. However, a small percentage of acute leukemia cases lack straightforward immunophenotypical lineage commitment. These leukemias of ambiguous lineage represent a heterogeneous category of acute leukemia that cannot be classified as either acute myeloid leukemia (AML) or acute lymphoid leukemia (ALL). The lack of clear classification of acute leukemias of ambiguous lineage as either AML or ALL is a hurdle in treatment choice for these patients. Here, we compared the microRNA (miRNA) expression profiles of 17 cases with acute leukemia of ambiguous lineage and 16 cases of AML, B-cell acute lymphoid leukemia (B-ALL), and T-cell acute lymphoid leukemia (T-ALL). We show that leukemias of ambiguous lineage do not segregate as a separate entity but exhibit miRNA expression profiles similar to AML, B-ALL, or T-ALL. We show that by using only 5 of the most lineage-discriminative miRNAs, we are able to define acute leukemia of ambiguous lineage as either AML or ALL. Our results indicate the presence of a myeloid or lymphoid lineage-specific genotype, as reflected by miRNA expression, in these acute leukemias despite their ambiguous immunophenotype. miRNA-based classification of acute leukemia of ambiguous lineage might be of additional value in therapeutic decision making.

  20. What Should You Ask Your Doctor about Acute Lymphocytic Leukemia?

    MedlinePlus

    ... Types What Should You Ask Your Doctor About Acute Lymphocytic Leukemia? It is important to have frank, honest discussions ... Your Doctor About Acute Lymphocytic Leukemia? More In Acute Lymphocytic Leukemia About Acute Lymphocytic Leukemia Causes, Risk Factors, and ...

  1. What Should You Ask Your Doctor about Chronic Lymphocytic Leukemia?

    MedlinePlus

    ... Should You Ask Your Doctor About Chronic Lymphocytic Leukemia? As you cope with cancer and cancer treatment, ... About Chronic Lymphocytic Leukemia? More In Chronic Lymphocytic Leukemia About Chronic Lymphocytic Leukemia Causes, Risk Factors, and ...

  2. What Should You Ask Your Doctor about Chronic Myeloid Leukemia?

    MedlinePlus

    ... Should You Ask Your Doctor About Chronic Myeloid Leukemia? As you cope with cancer and cancer treatment, ... About Chronic Myeloid Leukemia? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and ...

  3. What Are the Risk Factors for Chronic Myeloid Leukemia?

    MedlinePlus

    ... What Are the Risk Factors for Chronic Myeloid Leukemia? A risk factor is something that affects a ... Myeloid Leukemia Be Prevented? More In Chronic Myeloid Leukemia About Chronic Myeloid Leukemia Causes, Risk Factors, and ...

  4. What's New in Chronic Lymphocytic Leukemia Research and Treatment?

    MedlinePlus

    ... Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What's New in Chronic Lymphocytic Leukemia Research and Treatment? Many ... person's outlook and whether they will need treatment. New drugs for chronic lymphocytic leukemia Dozens of new ...

  5. Modulating Leukemia-Initiating Cell Quiescence to Improve Leukemia Treatment

    DTIC Science & Technology

    2015-09-01

    chromosome translocation. We utilized a mouse model of human acute myeloid leukemia (AML) induced by the MLL-AF9 oncogene to determine the role of Necdin...function as an endogenous anti-mitotic and anti-apoptotic protein in post-mitotic neurons [1]. The necdin gene is located on chromosome 15 in human and...Downing, J.R. (1996). AML1, the target of multiple chromosomal translocations in human leukemia, is essential for normal fetal liver hematopoiesis. Cell

  6. CCI-779 in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Myelodysplastic Syndromes, or Chronic Myelogenous Leukemia in Blastic Phase

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Myelodysplastic Syndromes

  7. Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants

    PubMed Central

    Driessen, Emma M.C.; van Roon, Eddy H.J.; Spijkers-Hagelstein, Jill A.P.; Schneider, Pauline; de Lorenzo, Paola; Valsecchi, Maria Grazia; Pieters, Rob; Stam, Ronald W.

    2013-01-01

    Acute lymphoblastic leukemia in infants represents an aggressive malignancy associated with a high incidence (approx. 80%) of translocations involving the Mixed Lineage Leukemia (MLL) gene. Attempts to mimic Mixed Lineage Leukemia fusion driven leukemogenesis in mice raised the question whether these fusion proteins require secondary hits. RAS mutations are suggested as candidates. Earlier results on the incidence of RAS mutations in Mixed Lineage Leukemia-rearranged acute lymphoblastic leukemia are inconclusive. Therefore, we studied frequencies and relation with clinical parameters of RAS mutations in a large cohort of infant acute lymphoblastic leukemia patients. Using conventional sequencing analysis, we screened neuroblastoma RAS viral (v-ras) oncogene homolog gene (NRAS), v-Ki-ras Kirsten rat sarcoma viral oncogene homolog gene (KRAS), and v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) for mutations in a large cohort (n=109) of infant acute lymphoblastic leukemia patients and studied the mutations in relation to several clinical parameters, and in relation to Homeobox gene A9 expression and the presence of ALL1 fused gene 4-Mixed Lineage Leukemia (AF4-MLL). Mutations were detected in approximately 14% of all cases, with a higher frequency of approximately 24% in t(4;11)-positive patients (P=0.04). Furthermore, we identified RAS mutations as an independent predictor (P=0.019) for poor outcome in Mixed Lineage Leukemia-rearranged infant acute lymphoblastic leukemia, with a hazard ratio of 3.194 (95% confidence interval (CI):1.211–8.429). Also, RAS-mutated infants have higher white blood cell counts at diagnosis (P=0.013), and are more resistant to glucocorticoids in vitro (P<0.05). Finally, we demonstrate that RAS mutations, and not the lack of Homeobox gene A9 expression nor the expression of AF4-MLL are associated with poor outcome in t(4;11)-rearranged infants. We conclude that the presence of RAS mutations in Mixed Lineage Leukemia

  8. Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-18

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. Vaccine Therapy Plus Immune Adjuvant in Treating Patients With Chronic Myeloid Leukemia, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-04

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Myeloid Leukemia in Remission; Chronic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  10. How Is Childhood Leukemia Classified?

    MedlinePlus

    ... Classification based on how the leukemia cells look (morphology) In the past, doctors used the French-American- ... of AML are classified mainly based on their morphology (how they look under the microscope). There are ...

  11. Pharmacogenetics in Acute Lymphoblastic Leukemia

    PubMed Central

    Cheok, Meyling H.; Pottier, Nicolas; Kager, Leo

    2009-01-01

    Progress in the treatment of acute leukemia in children has been remarkable, from a disease being lethal four decades ago to current cure rates exceeding 80%. This exemplary progress is largely due to the optimization of existing treatment modalities rather than the discovery of new antileukemic agents. However, despite these high cure rates, the annual number of children whose leukemia relapses after their initial therapy remains greater than that of new cases of most types of childhood cancers. The aim of pharmacogenetics is to develop strategies to personalize treatment and tailor therapy to individual patients, with the goal of optimizing efficacy and safety through better understanding of human genome variability and its influence on drug response. In this review, we summarize recent pharmacogenomic studies related to the treatment of pediatric acute lymphoblastic leukemia. These studies illustrate the promise of pharmacogenomics to further advance the treatment of human cancers, with childhood leukemia serving as a paradigm. PMID:19100367

  12. Down syndrome preleukemia and leukemia.

    PubMed

    Maloney, Kelly W; Taub, Jeffrey W; Ravindranath, Yaddanapudi; Roberts, Irene; Vyas, Paresh

    2015-02-01

    Children with Down syndrome (DS) and acute leukemias acute have unique biological, cytogenetic, and intrinsic factors that affect their treatment and outcome. Myeloid leukemia of Down syndrome (ML-DS) is associated with high event-free survival (EFS) rates and frequently preceded by a preleukemia condition, the transient abnormal hematopoiesis (TAM) present at birth. For acute lymphoblastic leukemia (ALL), their EFS and overall survival are poorer than non-DS ALL, it is important to enroll them on therapeutic trials, including relapse trials; investigate new agents that could potentially improve their leukemia-free survival; and strive to maximize the supportive care these patients need. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. PROGRESS IN ACUTE MYELOID LEUKEMIA

    PubMed Central

    Kadia, Tapan M.; Ravandi, Farhad; O’Brien, Susan; Cortes, Jorge; Kantarjian, Hagop M.

    2014-01-01

    Significant progress has been made in the treatment of acute myeloid leukemia (AML). Steady gains in clinical research and a renaissance of genomics in leukemia have led to improved outcomes. The recognition of tremendous heterogeneity in AML has allowed individualized treatments of specific disease entities within the context of patient age, cytogenetics, and mutational analysis. The following is a comprehensive review of the current state of AML therapy and a roadmap of our approach to these distinct disease entities. PMID:25441110

  14. Treatment of prolymphocytic leukemia

    SciTech Connect

    Hollister, S. Jr.; Coleman, M.

    1982-11-01

    Prolymphocytic leukemia is characterized by marked splenomegaly, distinctive cellular morphologic characteristics, and a poor clinical course. Five patients with typical PL were treated systematically with vincristine/prednisone, chlorambucil/prednisone, splenic irradiation, splenectomy, and other chemotherapy regimens. No patient responded to vincristine/prednisone. Two patients responded to chlorambucil/prednisone, and four patients had brief responses to splenic irradiation. Two patients underwent splenectomy, one of whom had a prolonged clinical remissions. No other chemotherapy combinations were of value. The median survival was 33 months. Recommendations are made to use chlorambucil/prednisone or splenic irradiation as initial treatment. Splenectomy should be considered in patients refractory to these modalities. The course of PL may be more protracted than originally reported.

  15. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-02-13

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  16. Diagnostic tools for hypersensitivity to platinum drugs and taxanes: skin testing, specific IgE, and mast cell/basophil mediators.

    PubMed

    Caiado, Joana; Picard, Matthieu

    2014-08-01

    Hypersensitivity reactions (HSRs) to platinum drugs and taxanes are increasing in cancer patients, and rapid drug desensitization has emerged as a safe and effective method to reintroduce these drugs in reactive patients. Optimal management of patients presenting HSRs to chemotherapy depends on the use of various diagnostic tools, which include measurement of mast cell/basophil mediator release following a HSR and skin testing. Serum tryptase should be measured in patients presenting chemotherapy HSRs, and its elevation would support mast cell/basophil activation. Skin testing to platinum drugs has a high sensitivity and specificity and is critical to guide the management of platinum-reactive patients. Taxane skin testing is also emerging as a useful diagnostic and risk stratification tool in the evaluation of patients with HSRs to taxanes. Platinum sIgE assays have been recently developed and can be helpful in combination with skin testing or as an alternative when skin testing is not available.

  17. Antibody Therapy for Pediatric Leukemia

    PubMed Central

    Vedi, Aditi; Ziegler, David S.

    2014-01-01

    Despite increasing cure rates for pediatric leukemia, relapsed disease still carries a poor prognosis with significant morbidity and mortality. Novel targeted therapies are currently being investigated in an attempt to reduce adverse events and improve survival outcomes. Antibody therapies represent a form of targeted therapy that offers a new treatment paradigm. Monoclonal antibodies are active in pediatric acute lymphoblastic leukemia (ALL) and are currently in Phase III trials. Antibody-drug conjugates (ADCs) are the next generation of antibodies where a highly potent cytotoxic agent is bound to an antibody by a linker, resulting in selective targeting of leukemia cells. ADCs are currently being tested in clinical trials for pediatric acute myeloid leukemia and ALL. Bispecific T cell engager (BiTE) antibodies are a construct whereby each antibody contains two binding sites, with one designed to engage the patient’s own immune system and the other to target malignant cells. BiTE antibodies show great promise as a novel and effective therapy for childhood leukemia. This review will outline recent developments in targeted agents for pediatric leukemia including monoclonal antibodies, ADCs, and BiTE antibodies. PMID:24795859

  18. Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-03-19

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  19. Is the Quantification of Antigen-Specific Basophil Activation a Useful Tool for Monitoring Oral Tolerance Induction in Children With Egg Allergy?

    PubMed

    Gamboa, P M; Garcia-Lirio, E; Gonzalez, C; Gonzalez, A; Martinez-Aranguren R M; Sanz María, L

    2016-01-01

    To assess modifications in baseline specific IgE- and anti-IgE- and antigen-specific-mediated basophil activation in egg-allergic children. The values were compared before and after the children completed specific oral tolerance induction (SOTI) with egg. We studied 28 egg-allergic children who completed SOTI with egg. The basophil activation test and specific IgE determinations with egg white, ovalbumin, and ovomucoid were performed in all 28 children. A decrease in antigen-specific activation with egg white, ovalbumin, and ovomucoid was observed only at the 2 lowest concentrations used (5 and 0.05 ng/mL). Baseline activation was higher in patients with multiple food allergies and in those who developed anaphylaxis during SOTI; this activation decreased in both groups after completion of SOTI. A significant decrease was also observed in specific IgE values for egg white, ovalbumin, and ovomucoid after tolerance induction. Food tolerance induction is a specific process for each food that can be mediated by immunologic changes such as a decrease in specific IgE values and in specific and spontaneous basophil activation.

  20. Anti-FcεR1 antibody injections activate basophils and mast cells and delay Type I diabetes onset in NOD mice

    PubMed Central

    Larson, David; Torrero, Marina N.; Mueller, Ellen; Shi, Yinghui; Killoran, Kristin

    2012-01-01

    Mounting evidence suggests that helminth infections protect against autoimmune diseases. As helminths cause chronic IgE-mediated activation of basophils and mast cells we hypothesized that continuous activation of these cells could prevents diabetes onset in nonobese diabetic (NOD) mice in the absence of infection. Anti-FcεR1 activated basophils and mast cells and resulted in the release of IL-4 and histamine into the bloodstream. Anti-FcεR1-treated NOD mice showed a type 2 shift in insulin-specific antibody production and exhibited significant delays in diabetes onset. IL-4 responses played a partial role as the protective effect of anti-FcεR1 therapy was diminished in IL-4-deficient NOD mice. In contrast, histamine signaling was not required as anti-FcεR1-mediated protection was not reduced in mice treated with histamine receptor blockers. These results demonstrate that anti-FcεR1 therapy delays diabetes onset in NOD mice and suggest that chronic basophil and mast cell activation may represent a new avenue of therapy for Th1-associated autoimmune diseases. PMID:21920822

  1. Cutting edge: IPSE/alpha-1, a glycoprotein from Schistosoma mansoni eggs, induces IgE-dependent, antigen-independent IL-4 production by murine basophils in vivo.

    PubMed

    Schramm, Gabriele; Mohrs, Katja; Wodrich, Maren; Doenhoff, Michael J; Pearce, Edward J; Haas, Helmut; Mohrs, Markus

    2007-05-15

    During infection with the helminth parasite Schistosoma mansoni, the deposition of eggs coincides with the onset of IL-4 production and Th2 development. Although IL-4 is known as a potent inducer of Th2 differentiation, the mechanism by which schistosome eggs induce IL-4 production is not clear. In this study, we demonstrate that the S. mansoni egg Ag (SmEA) induces IgE-dependent IL-4 production by basophils derived from Heligmosomoides polygyrus-infected or OVA/alum-immunized mice in the absence of pathogen-specific IgE. The effect is mediated by the secretory glycoprotein IPSE/alpha-1, because IPSE/alpha-1-depleted SmEA no longer induces cytokine production. Conversely, recombinant IPSE/alpha-1 is sufficient to induce IL-4 production. Importantly, the injection of SmEA or recombinant IPSE/alpha-1 into H. polygyrus-infected 4get/KN2 IL-4 reporter mice rapidly induces the dose-dependent IL-4 production by basophils in the liver, a major site of egg deposition. Thus, IPSE/alpha-1 induces basophils to produce IL-4 even in the absence of Ag-specific IgE.

  2. Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils.

    PubMed

    Rodríguez-Romero, Adela; Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira; Palomares, Laura A; Muñoz-Cruz, Samira; Yépez-Mulia, Lilian; Orozco-Martínez, Socorro

    2014-02-01

    Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyroglutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein.

  3. Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils

    PubMed Central

    Rodríguez-Romero, Adela; Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira; Palomares, Laura A.; Muñoz-Cruz, Samira; Yépez-Mulia, Lilian; Orozco-Martínez, Socorro

    2014-01-01

    Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyro­glutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein. PMID:24531467

  4. Mechanisms of Graft-vs.-Leukemia against a Novel Murine Model of Chronic Myelogenous Leukemia

    DTIC Science & Technology

    2006-07-01

    AD_________________ Award Number: DAMD17-03-1-0311 TITLE: Mechanisms of Graft-vs.- Leukemia ...against a Novel Murine Model of Chronic Myelogenous Leukemia PRINCIPAL INVESTIGATOR: Warren D. Shlomchik, M.D. CONTRACTING ORGANIZATION...5a. CONTRACT NUMBER Mechanisms of Graft-vs.- Leukemia against a Novel Murine Model of Chronic Myelogenous Leukemia 5b. GRANT NUMBER DAMD17

  5. Immunohistochemical identification of messenger RNA-related proteins in basophilic inclusions of adult-onset atypical motor neuron disease.

    PubMed

    Fujita, Kengo; Ito, Hidefumi; Nakano, Satoshi; Kinoshita, Yoshimi; Wate, Reika; Kusaka, Hirofumi

    2008-10-01

    This report concerns an immunohistochemical investigation on RNA-related proteins in the basophilic inclusions (BIs) from patients with adult-onset atypical motor neuron disease. Formalin-fixed, paraffin-embedded sections of the motor cortex and the lumbar spinal cord were examined. The BIs appeared blue in color with H&E and Nissl stain, and pink with methylgreen-pyronin stain. Ribonuclease pretreatment abolished the methylgreen-pyronin staining, suggesting that the BIs contained RNA. Immunohistochemically, the BIs were distinctly labeled with the antibodies against poly(A)-binding protein 1, T cell intracellular antigen 1, and ribosomal protein S6. These proteins are essential constituents of stress granules. In contrast, the BIs were not immunoreactive for ribosomal protein L28 and decapping enzyme 1, which are core components of transport ribonucleoprotein particles and processing bodies, respectively. Moreover, the BIs were not immunopositive for TDP-43. Our results imply that translation attenuation could be involved in the processes of BI formation in this disorder.

  6. Phase I/II Study of Nilotinib/Ruxolitinb Therapy for TKI Resistant Ph-Leukemia

    ClinicalTrials.gov

    2016-03-04

    Chronic Phase Chronic Myeloid Leukemia; Accelerated Phase Chronic Myeloid Leukemia; Blastic Phase Chronic Myeloid Leukemia; Philadelphia Positive Acute Lymphoblastic Leukemia; Resistant to Tyrosine Kinase Inhibitor Therapy

  7. 8-Chloro-Adenosine in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-11-08

    Recurrent Adult Acute Myeloid Leukemia; Relapsed Adult Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia Arising From Previous Myeloproliferative Disorder

  8. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis.

    PubMed

    Obiozor, Cynthia; Ganguly, Siddhartha; Fraga, Garth R

    2015-08-15

    Leukemia cutis describes cutaneous lesions produced by infiltrates of leukemic cells. It usually manifests contemporaneously with the initial diagnosis of systemic leukemia, but may also precede or follow systemic leukemia. Most cases are associated with acute myeloid leukemia. Adult B-cell lymphoblastic leukemia cutis is very rare. We report a 59-year-old woman with a history of B-cell acute lymphoblastic leukemia who relapsed with aleukemic lymphoblastic leukemia cutis. Lymphoglandular bodies were conspicuous on biopsy and may serve as a morphologic clue to lymphocytic differentiation while molecular and immunophenotypic studies are pending. The patient was successfully treated with local radiation therapy and oral ponatinib.

  9. How Is Acute Lymphocytic Leukemia Diagnosed?

    MedlinePlus

    ... Adults Early Detection, Diagnosis, and Types How Is Acute Lymphocytic Leukemia Diagnosed? Certain signs and symptoms can suggest that ... described below. Tests used to diagnose and classify ALL If your doctor thinks you have leukemia, he ...

  10. The Childhood Leukemia International Consortium

    PubMed Central

    Metayer, Catherine; Milne, Elizabeth; Clavel, Jacqueline; Infante-Rivard, Claire; Petridou, Eleni; Taylor, Malcolm; Schüz, Joachim; Spector, Logan G.; Dockerty, John D.; Magnani, Corrado; Pombo-de-Oliveira, Maria S.; Sinnett, Daniel; Murphy, Michael; Roman, Eve; Monge, Patricia; Ezzat, Sameera; Mueller, Beth A.; Scheurer, Michael E.; Armstrong, Bruce K.; Birch, Jill; Kaatsch, Peter; Koifman, Sergio; Lightfoot, Tracy; Bhatti, Parveen; Bondy, Melissa L.; Rudant, Jérémie; O’Neill, Kate; Miligi, Lucia; Dessypris, Nick; Kang, Alice Y.; Buffler, Patricia A.

    2013-01-01

    Background Acute leukemia is the most common cancer in children under 15 years of age; 80% are acute lymphoblastic leukemia (ALL) and 17% are acute myeloid leukemia (AML). Childhood leukemia shows further diversity based on cytogenetic and molecular characteristics, which may relate to distinct etiologies. Case–control studies conducted worldwide, particularly of ALL, have collected a wealth of data on potential risk factors and in some studies, biospecimens. There is growing evidence for the role of infectious/immunologic factors, fetal growth, and several environmental factors in the etiology of childhood ALL. The risk of childhood leukemia, like other complex diseases, is likely to be influenced both by independent and interactive effects of genes and environmental exposures. While some studies have analyzed the role of genetic variants, few have been sufficiently powered to investigate gene–environment interactions. Objectives The Childhood Leukemia International Consortium (CLIC) was established in 2007 to promote investigations of rarer exposures, gene–environment interactions and subtype-specific associations through the pooling of data from independent studies. Methods By September 2012, CLIC included 22 studies (recruitment period: 1962–present) from 12 countries, totaling approximately 31 000 cases and 50 000 controls. Of these, 19 case–control studies have collected detailed epidemiologic data, and DNA samples have been collected from children and child–parent trios in 15 and 13 of these studies, respectively. Two registry-based studies and one study comprising hospital records routinely obtained at birth and/or diagnosis have limited interview data or biospecimens. Conclusions CLIC provides a unique opportunity to fill gaps in knowledge about the role of environmental and genetic risk factors, critical windows of exposure, the effects of gene–environment interactions and associations among specific leukemia subtypes in different ethnic

  11. Childhood leukemia in Woburn, Massachusetts.

    PubMed Central

    Cutler, J J; Parker, G S; Rosen, S; Prenney, B; Healey, R; Caldwell, G G

    1986-01-01

    Possible associations between environmental hazards and the occurrence of childhood leukemia were investigated in Woburn, MA, for the period 1969-79. Residents of Woburn were concerned over what they perceived to be a large number of childhood leukemia cases; at the same time there was extensive publicity about uncontrolled hazardous waste sites in Woburn, which resulted in its being placed on the Superfund list. Many believed that the elevated rate of childhood leukemia was related to these sites or to two city water wells that had been closed in 1979 when they were found to be contaminated by organic chemicals. An occurrence was defined as childhood leukemia when it was diagnosed in a Woburn resident less than 20 years old between 1969 and 1979 and confirmed by review of hospital and pathology records. This investigation confirmed an increase in incidence which was distributed uniformly over the 11-year period. Six of the persons with leukemia were located close to each other in one census tract, 7.5 times the expected number. Parents of the children and of two matched control groups were interviewed about medical history, mother's pregnancy history, school history, and environmental exposures. There were no significant differences between the leukemia victims and persons in the control groups. No leukemia sufferer had contact with a hazardous waste site. While the contaminants of Wells G and H, which had been closed, are not known leukemogens, it is not possible to rule out exposure to this water as a factor, particularly in the eastern Woburn residents. PMID:3083476

  12. Subthreshold desensitization of human basophils re-capitulates the loss of Syk and FcεRI expression characterized by other methods of desensitization.

    PubMed

    MacGlashan, D

    2012-07-01

    Clinical desensitization of patients to drugs involves progressive exposure to escalating doses of drug over a period of 24 h. In prior studies, this method was re-capitulated in vitro to also demonstrate loss of mast cell or basophil responsiveness. However, most signalling studies of human basophils have identified changes in signalling by using other methods of inducing cellular desensitization. This study examined two well-described endpoints of basophil desensitization, loss of syk or FcεRI expression, under conditions of subthreshold desensitization. The loss of FcεRI and syk was examined in human basophils. It was shown that both loss of syk and FcεRI/IgE occurred during an escalating series of stimulation (anti-IgE Ab) and that expression loss occurred despite the presence of little histamine release. If basophils were first cultured for 3 days in 10 ng/mL IL-3, the concentration-dependence of histamine release shifted to 100-fold lower concentrations of stimulus. However, loss of syk did not show any change in its EC50 while loss of FcεRI also shifted 100-fold. From the perspective of early signal element activation, the marked shift in the EC50 for histamine release was not accompanied by similar shifts in the EC50s for several signalling elements. The EC50s for phospho-Src, phospho-SHIP1, phospho-Syk, or phospho-Cbl did not change while the EC50s for phospho-Erk and the cytosolic calcium response did shift 100-fold. These studies show that under normal conditions, subthreshold desensitization leads to loss of two critical signalling molecules (FcεRI and syk) but under at least one condition, treatment with IL-3, it is possible to markedly blunt the loss of syk, but not FcεRI, while executing a proper subthreshold titration. These data also suggest that IL-3 modifies only the sensitivity of signalling elements that are downstream of syk activation. © 2012 Blackwell Publishing Ltd.

  13. Subthreshold Desensitization of Human Basophils Re-capitulates the Loss of syk and FcεRI expression Characterized by Other Methods of Desensitization

    PubMed Central

    MacGlashan, Donald

    2012-01-01

    Background Clinical desensitization of patients to drugs involves progressive exposure to escalating doses of drug over a period of 24 hours. In prior studies, this method was recapitulated in vitro to also demonstrate loss of mast cell or basophil responsiveness. However, most signaling studies of human basophils have identified changes in signaling by using other methods of inducing cellular desensitization. Objective This study examined two well-described endpoints of basophil desensitization, loss of syk or FcεRI expression, under conditions of subthreshold desensitization. Methods The loss of FceRI and syk was examined in human basophils. Results It was shown that both loss of syk and FcεRI/IgE occurred during an escalating series of stimulation (anti-IgE Ab) and that expression loss occurred despite the presence of little histamine release. If basophils were first cultured for 3 days in 10 ng/ml IL-3, the concentration-dependence of histamine release shifted to 100 fold lower concentrations of stimulus. However, loss of syk did not show any change in its EC50 while loss of FcεRI also shifted 100 fold. From the perspective of early signal element activation, the marked shift in the EC50 for histamine release was not accompanied by similar shifts in the EC50s for several signaling elements. The EC50s for phospho-Src, phospho-SHIP1, phospho-Syk, or phospho-Cbl did not change while the EC50s for phospho-Erk and the cytosolic calcium response did shift 100 fold. Conclusions These studies show that under normal conditions, subthreshold desensitization leads to loss of two critical signaling molecules (FcεRI and syk) but under at least one condition, treatment with IL-3, it is possible to markedly blunt the loss of syk, but not FcεRI, while executing a proper subthreshold titration. These data also suggest that IL-3 modifies only the sensitivity of signaling elements that are downstream of syk activation. PMID:22702505

  14. PS-341 in Treating Patients With Refractory or Relapsed Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myeloid Leukemia in Blast Phase, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  15. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    MedlinePlus

    ... 1- to 2-Year-Old Acute Lymphoblastic Leukemia (ALL) KidsHealth > For Parents > Acute Lymphoblastic Leukemia (ALL) A A A What's in this article? About ... child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood ...

  16. Acute leukemias of ambiguous origin.

    PubMed

    Porwit, Anna; Béné, Marie C

    2015-09-01

    This session of the Society for Hematopathology/European Association for Haematopathology Workshop focused on acute leukemias of ambiguous origin. We provide an overview of mixed-phenotype acute leukemia (MPAL) as recognized in the current World Health Organization classification and summarize diagnostic criteria for major categories of MPAL: B/myeloid, T/myeloid, B/T, and B/T/myeloid. Most MPAL cases submitted were B/myeloid and T/myeloid MPAL, the most frequent types, but three cases of B/T MPAL were also submitted, and examples of all categories are illustrated. We emphasize that a comprehensive approach to immunophenotyping is required to accurately establish the diagnosis of MPAL. Flow cytometry immunophenotyping using a large panel of antibodies is needed as well as confirmatory immunohistochemical analysis and cytochemistry studies for myeloperoxidase and nonspecific esterase. We discuss technical issues in determining blast lineage and possible pitfalls in MPAL diagnosis. In particular, rare cases of B-acute lymphoblastic leukemia (B-ALL) can express myeloperoxidase but are otherwise consistent with B-ALL and should be treated as such. Last, we review the differential diagnosis between acute undifferentiated leukemia and acute myeloid leukemia with minimal differentiation. There was an agreement that diagnosis of MPAL can be challenging, especially if applied flow cytometry panels are not comprehensive enough. Copyright© by the American Society for Clinical Pathology.

  17. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    ClinicalTrials.gov

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  18. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  19. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-04-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  20. Leukemia inhibitory factor (LIF).

    PubMed

    Nicola, Nicos A; Babon, Jeffrey J

    2015-10-01

    Leukemia inhibitory factor (LIF) is the most pleiotropic member of the interleukin-6 family of cytokines. It utilises a receptor that consists of the LIF receptor β and gp130 and this receptor complex is also used by ciliary neurotrophic growth factor (CNTF), oncostatin M, cardiotrophin1 (CT1) and cardiotrophin-like cytokine (CLC). Despite common signal transduction mechanisms (JAK/STAT, MAPK and PI3K) LIF can have paradoxically opposite effects in different cell types including stimulating or inhibiting each of cell proliferation, differentiation and survival. While LIF can act on a wide range of cell types, LIF knockout mice have revealed that many of these actions are not apparent during ordinary development and that they may be the result of induced LIF expression during tissue damage or injury. Nevertheless LIF does appear to have non-redundant actions in maternal receptivity to blastocyst implantation, placental formation and in the development of the nervous system. LIF has also found practical use in the maintenance of self-renewal and totipotency of embryonic stem cells and induced pluripotent stem cells. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Chronic Lymphocytic Leukemia

    PubMed Central

    Motta, Marina; Wierda, William G.; Ferrajoli, Alessandra

    2015-01-01

    Patients with purine analogue-refractory chronic lymphocytic leukemia (CLL) have short survival and limited treatment options. Defining the best salvage strategies for this population is challenging, because limited data are available from clinical trials, and because studies have enrolled mixed populations (patients with recurrent and refractory disease or patients with refractory disease and Richter transformation). Moreover, patients with refractory CLL have a high incidence of unfavorable molecular and clinical features, such as high-risk genomic profiles, unmutated immunoglobulin heavy-chain genes, expression of zeta-chain-associated protein kinase 70, and bulky lymphadenopathies. These patients are also severely immunosuppressed because of the underlying disease and the treatments received, and experience a high rate of infectious complications that pose an additional difficulty in selecting treatment. Despite these challenges, in parallel with better characterizations of the biologic features of refractory CLL, the number of available treatment modalities for this population has increased. Several chemoimmunotherapy combinations have been developed, and novel agents with a different mechanism of action are being investigated in clinical trials. Furthermore, allogeneic stem cell transplantation with nonmyeloablative conditioning regimens is a therapeutic strategy that is increasingly offered to patients with refractory CLL. PMID:19536902

  2. Leukemia Inhibitory Factor (LIF)

    PubMed Central

    Nicola, Nicos A; Babon, Jeffrey J

    2015-01-01

    Leukemia inhibitory factor (LIF) is the most pleiotropic member of the interleukin-6 family of cytokines. It utilises a receptor that consists of the LIF receptor β and gp130 and this receptor complex is also used by ciliary neurotrophic growth factor (CNTF), oncostatin M, cardiotrophin1 (CT1) and cardiotrophin-like cytokine (CLC). Despite common signal transduction mechanisms (JAK/STAT, MAPK and PI3K) LIF can have paradoxically opposite effects in different cell types including stimulating or inhibiting each of cell proliferation, differentiation and survival. While LIF can act on a wide range of cell types, LIF knockout mice have revealed that many of these actions are not apparent during ordinary development and that they may be the result of induced LIF expression during tissue damage or injury. Nevertheless LIF does appear to have non-redundant actions in maternal receptivity to blastocyst implantation, placental formation and in the development of the nervous system. LIF has also found practical use in the maintenance of self-renewal and totipotency of embryonic stem cells and induced pluripotent stem cells. PMID:26187859

  3. PLASMA CELL LEUKEMIA

    PubMed Central

    de Larrea, Carlos Fernandez; Kyle, Robert A.; Durie, Brian GM; Ludwig, Heinz; Usmani, Saad; Vesole, David H.; Hajek, Roman; Miguel, Jésus San; Sezer, Orhan; Sonneveld, Pieter; Kumar, Shaji K.; Mahindra, Anuj; Comenzo, Ray; Palumbo, Antonio; Mazumber, Amitabha; Anderson, Kenneth C.; Richardson, Paul G.; Badros, Ashraf Z.; Caers, Jo; Cavo, Michele; LeLeu, Xavier; Dimopoulos, Meletios A.; Chim, CS; Schots, Rik; Noeul, Amara; Fantl, Dorotea; Mellqvist, Ulf-Henrik; Landgren, Ola; Chanan-Khan, Asher; Moreau, Philippe; Fonseca, Rafael; Merlini, Giampaolo; Lahuerta, JJ; Bladé, Joan; Orlowski, Robert Z.; Shah, Jatin J.

    2014-01-01

    Plasma cell leukemia (PCL) is a rare and aggressive variant of myeloma characterized by the presence of circulating plasma cells. It is classified as either primary PCL occurring at diagnosis or as secondary PCL in patients with relapsed/refractory myeloma. Primary PCL is a distinct clinic-pathologic entity with different cytogenetic and molecular findings. The clinical course is aggressive with short remissions and survival duration. The diagnosis is based upon the percentage (≥ 20%) and absolute number (≥ 2 × 10 9/L) of plasma cells in the peripheral blood. It is proposed that the thresholds for diagnosis be reexamined and consensus recommendations are made for diagnosis, as well as, response and progression criteria. Induction therapy needs to begin promptly and have high clinical activity leading to rapid disease control in an effort to minimize the risk of early death. Intensive chemotherapy regimens and bortezomib-based regimens are recommended followed by high-dose therapy with autologous stem-cell transplantation (HDT/ASCT) if feasible. Allogeneic transplantation can be considered in younger patients. Prospective multicenter studies are required to provide revised definitions and better understanding of the pathogenesis of PCL. PMID:23288300

  4. Decitabine With or Without Bortezomib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-08-30

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. Bullous leukemia cutis mimicking facial cellulitis*

    PubMed Central

    Caldato, Luciana de Sales; Britto, Juliana de Sousa; Niero-Melo, Ligia; Miot, Hélio Amante

    2016-01-01

    Bullous leukemia cutis is an uncommon clinical manifestation of cutaneous infiltration by leukemic cells, from B-cell chronic lymphocytic leukemia. We present the case of a 67-year-old, female, chronic lymphocytic leukemia patient. She was taking chlorambucil and developed facial edema with erythema and warmth, misjudged as facial cellulitis. Two days later, she developed bullous lesions in the arms, legs, neck and face. The histopathology of facial and bullous lesions confirmed leukemia cutis. All lesions disappeared following the administration of rituximab combined with cycles of fludarabine and cyclophosphamide. Although soft tissue infections are common complications in patients undergoing chemotherapy, leukemia cutis can also resemble cellulitis. PMID:27192532

  6. Vaccinium angustifolium Root Extract Suppresses FcɛRI Expression in Human Basophilic KU812F Cells

    PubMed Central

    Shim, Sun Yup; Lee, Kyung Dong; Lee, Mina

    2017-01-01

    Vaccinium angustifolium, commonly known as the lowbush blueberry, is a rich source of flavonoids, with which various human physiological activities have been associated. The present study focuses on the investigation of the effect of the methanolic extract of V. angustifolium root extract (VAE) on high affinity immunoglobulin E receptor (FcɛRI) α chain antibody (CRA-1)-induced allergic reaction in human basophilic KU812F cells. The total phenolic content of VAE was found to be 170±1.9 mg gallic acid equivalents/g. Flow cytometry analysis revealed that the cell surface expression of FcɛRI was suppressed in a concentration-dependent manner upon culture with VAE. Reverse-transcriptase polymerase chain reaction analysis showed that the mRNA level of the FcɛRI α chain was reduced in a concentration-dependent manner as a result of VAE treatment. Western blot analysis revealed that the protein expression of FcɛRI and the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2 were concentration-dependently inhibited by VAE. We determined that VAE inhibited anti-CRA-1-induced histamine release, in addition to the elevation of intracellular calcium concentration ([Ca2+]i), in a concentration-dependent manner. These results indicate that VAE may exert an anti-allergic effect via the inhibition of calcium influx and histamine release, which occurs as a result of the down-regulation of FcɛRI expression through inhibition of ERK 1/2 activation. PMID:28401082

  7. Vaccinium angustifolium Root Extract Suppresses FcɛRI Expression in Human Basophilic KU812F Cells.

    PubMed

    Shim, Sun Yup; Lee, Kyung Dong; Lee, Mina

    2017-03-01

    Vaccinium angustifolium, commonly known as the lowbush blueberry, is a rich source of flavonoids, with which various human physiological activities have been associated. The present study focuses on the investigation of the effect of the methanolic extract of V. angustifolium root extract (VAE) on high affinity immunoglobulin E receptor (FcɛRI) α chain antibody (CRA-1)-induced allergic reaction in human basophilic KU812F cells. The total phenolic content of VAE was found to be 170±1.9 mg gallic acid equivalents/g. Flow cytometry analysis revealed that the cell surface expression of FcɛRI was suppressed in a concentration-dependent manner upon culture with VAE. Reverse-transcriptase polymerase chain reaction analysis showed that the mRNA level of the FcɛRI α chain was reduced in a concentration-dependent manner as a result of VAE treatment. Western blot analysis revealed that the protein expression of FcɛRI and the phosphorylation of extracellular signal-regulated kinases (ERK) 1/2 were concentration-dependently inhibited by VAE. We determined that VAE inhibited anti-CRA-1-induced histamine release, in addition to the elevation of intracellular calcium concentration ([Ca(2+)]i), in a concentration-dependent manner. These results indicate that VAE may exert an anti-allergic effect via the inhibition of calcium influx and histamine release, which occurs as a result of the down-regulation of FcɛRI expression through inhibition of ERK 1/2 activation.

  8. Leukemia cutis in a patient with chronic lymphocytic leukemia presenting as bilateral helical nodules

    PubMed Central

    Raufi, Ali; Alsharedi, Mohamed; Khelfa, Yousef; Griswold, Doreen C; Lebowicz, Yehuda

    2016-01-01

    Chronic lymphocytic leukemia, the most common adult leukemia worldwide, is considered an indolent but incurable non-Hodgkin lymphoma. Leukemia cutis is an uncommon manifestation of chronic lymphocytic leukemia. We present a case of an adult patient who presented with skin lesion of bilateral ears, which led to the diagnosis of chronic lymphocytic leukemia. We also reviewed the cases of auricular involvement in chronic lymphocytic leukemia patients reported in the literature. Local treatment is indicated in case of leukemia cutis; however, systemic treatment is recommended when there are systemic signs and symptoms. Better awareness of disease evolution and prompt diagnosis of this leukemia cutis of chronic lymphocytic leukemia will improve the effectiveness and outcome of its management. PMID:28228955

  9. Infection and childhood leukemia: review of evidence

    PubMed Central

    Maia, Raquel da Rocha Paiva; Wünsch, Victor

    2013-01-01

    OBJECTIVE To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors "childhood leukemia" and "infection" and later searching for the words "childhood leukemia" and "maternal infection or disease" or "breastfeeding" or "daycare attendance" or "vaccination" resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers' or infants' to infections (or proxy of infection), and risk of leukemia. RESULTS Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori. CONCLUSIONS Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology. PMID:24626555

  10. Applying molecular epidemiology in pediatric leukemia.

    PubMed

    Schiffman, Joshua D

    2016-02-01

    Molecular epidemiology is the study of genetic and environmental risk for disease, with much effort centered on cancer. Childhood leukemia occurs in nearly a third of all patients newly diagnosed with pediatric cancer. only a small percentage of these new cases of childhood leukemia are associated with high penetrant hereditary cancer syndromes. Childhood leukemia, especially acute lymphoblastic leukemia, has been associated with a dysregulated immune system due to delayed infectious exposure at a young age. Identical twins with childhood leukemia suggest that acute lymphoblastic leukemia begins in utero and that the concordant presentation is due to a shared preleukemia subclone via placental transfer. Investigation of single nucleotide polymorphisms within candidate genes find that leukemia risk may be attributed to population-based polymorphisms affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies for leukemia risk has led investigators to genes associated with B-cell development. When describing leukemia predisposition due to hereditary cancer syndromes, the following 6 categories become apparent on the basis of biology and clinical presentation: (1) genetic instability/DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription factor syndromes and pure familial leukemia. understanding the molecular epidemiology of childhood leukemia can affect the treatment and tumor surveillance strategies for these high risk patients and their family members.

  11. Plasma cell leukemia.

    PubMed

    Albarracin, Flavio; Fonseca, Rafael

    2011-05-01

    Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/μL and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations.

  12. Plasma cell leukemia

    PubMed Central

    Albarracin, Flavio; Fonseca, Rafael

    2014-01-01

    Plasma cell leukemia (PCL) is a rare, yet aggressive plasma cell (PC) neoplasm, variant of multiple myeloma (MM), characterized by high levels of PCs circulating in the peripheral blood. PCL can either originate de novo (primary PCL) or as a secondary leukemic transformation of MM (secondary PCL). Presenting signs and symptoms are similar to those seen in MM such as renal insufficiency, hypercalcemia, lytic bone lesions, anemia, and thrombocytopenia, but can also include hepatomegaly and splenomegaly. The diagnostic evaluation of a patient with suspected PCL should include a review of the peripheral blood smear, bone marrow aspiration and biopsy, serum protein electrophoresis (SPEP) with immunofixation, and protein electrophoresis of an aliquot from a 24h urine collection (UPEP). The diagnosis is made when a monoclonal population of PCs is present in the peripheral blood with an absolute PC count exceeding 2000/μL and PC comprising 20% or more of the peripheral blood white cells. The prognosis of PCL is poor with a median survival of 7 to 11 months. Survival is even shorter (2 to 7 months) when PCL occurs in the context of refractory or relapsing MM. There have been no prospective randomized trials investigating the treatment of PCL. Recommendations are primarily based upon data from small retrospective series, case reports, and extrapolation of data from patients with MM. In general, patients are treated with induction therapy followed by hematopoietic cell transplantation (HCT) in those who are appropriate candidates for this approach. The best induction regimen for PCL is not known and there is great variability in clinical practice. Newer agents that are being incorporated into frontline and salvage therapy for MM have also demonstrated activity in PCL such as Immunomodulatory agents and the use of bortezomib with different combinations. PMID:21295388

  13. Association of leukemia with radium groundwater contamination.

    PubMed

    Lyman, G H; Lyman, C G; Johnson, W

    1985-08-02

    Radiation exposure, including the ingestion of radium, has been causally associated with leukemia in man. Groundwater samples from 27 counties on or near Florida phosphate lands were found to exceed 5 pCi/L total radium in 12.4% of measurements. The incidence of leukemia was greater in those counties with high levels of radium contamination (greater than 10% of the samples contaminated) than in those with low levels of contamination. Rank correlation coefficients of .56 and .45 were observed between the radium contamination level and the incidence of total leukemia and acute myeloid leukemia, respectively. The standardized incidence density ratio for those in high-contamination counties was 1.5 for total leukemia and 2.0 for acute myeloid leukemia. Further investigation is necessary, however, before a causal relationship between groundwater radium content and human leukemia can be established.

  14. GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-12-03

    Acute Undifferentiated Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  15. Very late recurrences of leukemia: why does leukemia awake after many years of dormancy?

    PubMed

    Norkin, Maxim; Uberti, Joseph P; Schiffer, Charles A

    2011-02-01

    We report a heterogeneous group of very late recurrences of leukemia occurring more than 10 years after initial treatment including 2 cases of childhood acute lymphoblastic leukemia (ALL) which recurred after more than 20 years of remission, 2 cases of donor cell leukemia which developed more than 10 years after allograft for acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) and 2 cases of chronic myeloid leukemia (CML) relapsing 13 and 17 years after allograft. Case descriptions are followed by a discussion regarding possible mechanisms leading to leukemia recurrence and a review of the literature. Copyright © 2010 Elsevier Ltd. All rights reserved.

  16. Transformation of Rat and Hamster Embryo Cells by Extracts of City Smog

    PubMed Central

    Freeman, Aaron E.; Price, Paul J.; Bryan, Robert J.; Gordon, Robert J.; Gilden, Raymond V.; Kelloff, Gary J.; Huebner, Robert J.

    1971-01-01

    Extracts of particulate matter from condensates of city air were tested for their ability to transform rat or hamster cell cultures. Uninfected rat embryo cultures were not transformed, but cultures chronically infected with Rauscher leukemia virus were transformed by benzpyrene or by extracts of city smog. The smog extracts were 600 times more active than pure benzpyrene as transforming agents. Hamster embryo cultures infected with hamster leukemia virus were equally as sensitive as leukemia-infected rat cultures to the transforming effects of smog; uninfected hamster cultures were also transformed, although tenfold higher doses of smog extract were required. Images PMID:5277098

  17. Structural analysis of the endogenous glycoallergen Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis and its recognition by human basophils

    SciTech Connect

    Rodríguez-Romero, Adela Hernández-Santoyo, Alejandra; Fuentes-Silva, Deyanira; Palomares, Laura A.; Muñoz-Cruz, Samira; Yépez-Mulia, Lilian; Orozco-Martínez, Socorro

    2014-02-01

    This study describes the three-dimensional structure of the endogenous glycosylated allergen Hev b 2 (endo-β-1,3-glucanase), which exhibits three post-translational modifications that form a patch on the surface of the molecule that is proposed to be an allergenic IgE epitope. Endogenous glycosylated Hev b 2 (endo-β-1,3-glucanase) from Hevea brasiliensis is an important latex allergen that is recognized by IgE antibodies from patients who suffer from latex allergy. The carbohydrate moieties of Hev b 2 constitute a potentially important IgE-binding epitope that could be responsible for its cross-reactivity. Here, the structure of the endogenous isoform II of Hev b 2 that exhibits three post-translational modifications, including an N-terminal pyroglutamate and two glycosylation sites at Asn27 and at Asn314, is reported from two crystal polymorphs. These modifications form a patch on the surface of the molecule that is proposed to be one of the binding sites for IgE. A structure is also proposed for the most important N-glycan present in this protein as determined by digestion with specific enzymes. To analyze the role of the carbohydrate moieties in IgE antibody binding and in human basophil activation, the glycoallergen was enzymatically deglycosylated and evaluated. Time-lapse automated video microscopy of basophils stimulated with glycosylated Hev b 2 revealed basophil activation and degranulation. Immunological studies suggested that carbohydrates on Hev b 2 represent an allergenic IgE epitope. In addition, a dimer was found in each asymmetric unit that may reflect a regulatory mechanism of this plant defence protein.

  18. Test of a theory relating to the cross-linking of IgE antibody on the surface of human basophils

    SciTech Connect

    MacGlashan, D.W. Jr.; Dembo, M.; Goldstein, B.

    1985-12-01

    Recent mathematical models of bivalent hapten-induced histamine release from basophils predict that under appropriate conditions histamine release is maximum when cross-link formation is maximum, at a hapten concentration equal to 1/(2K/sub a/), where K/sub a/ is the average affinity constant of the hapten for a single IgE binding site. To test this prediction the authors sensitized human basophils with a monoclonal anti-dinitrophenol IgE and generated histamine release dose-response curves with a bivalent hapten, ..cap alpha..,epsilon-DNP-lysine. The monoclonal IgE has a published affinity constant of 7.1 x 10/sup 7/ M/sup -1/ for epsilon-DNP-lysine as determined by equilibrium dialysis. From the position of the maximum of the histamine dose-response curves, both in the presence and in the absence of monovalent DNP hapten, the authors determine that the sensitizing IgE has an intrinsic affinity constant of 6.9 +/- 0.5 x 10/sup 7/ M/sup -1/ for such that-DNP-lysine and 1.2 +/- 0.6 x 10/sup 6/ M/sup -1/ for ..cap alpha..-DNP-lysine. The agreement between the two estimates of the epsilon-DNP-lysine affinity constant, one from histamine release experiments involving surface bound IgE and one from binding experiments involving IgE free in solution, 1) is consistent with a central prediction of the theory of cross-linking and 2) indicates that the hapten-binding properties of the IgE are unaffected by its being bound to Fc/sub epsilon/ receptors on the basophil surface. 30 references, 3 figures, 3 tables.

  19. Evaluation of basophil allergen threshold sensitivity (CD-sens) to peanut and Ara h 8 in children IgE-sensitized to Ara h 8.

    PubMed

    Glaumann, Susanne; Nilsson, Caroline; Johansson, S G O; Asarnoj, Anna; Wickman, Magnus; Borres, Magnus P; Nopp, Anna

    2015-01-01

    Diagnosing peanut allergy properly is important and can be achieved by combining clinical history with various diagnostic methods such as IgE-antibody (IgE-ab) measurements, skin-prick test, basophil allergen threshold sensitivity (CD-sens) and food challenge. We aimed to evaluate CD-sens to peanut, Ara h 8 and Gly m 4 in relation to an oral peanut challenge in children IgE-sensitized to birch, peanut and Ara h 8 avoiding peanuts. Twenty children IgE-sensitized to birch pollen and Ara h 8, but not to Ara h 1, Ara h 2 or Ara h 3 were challenged orally with roasted peanuts. Blood samples were drawn for IgE-ab and CD-sens analysis. To measure CD-sens, basophils were stimulated in vitro with decreasing doses of allergens until threshold sensitivity was reached. All children passed challenge without objective symptoms, but mild oral allergy syndrome (OAS) symptoms were reported in 6/20 children. Nineteen of twenty children were negative in CD-sens to peanut but 17/20 were positive to rAra h 8. Eleven of twenty children were positive in CD-sens to rGly m 4. Positive CD-sens to rAra h 8 show that the Ara h 8 IgE-ab sensitized basophils can be activated by a rAra h 8 allergen and initiate an allergic inflammation despite a negative challenge. Hence, children sensitized to Ara h 8 but not to peanut storage proteins may be at risk for systemic allergic reaction when eating larger amounts of peanuts but most likely don't have to fear smaller amounts.

  20. Targeting Mast Cells and Basophils with Anti-FcεRIα Fab-Conjugated Celastrol-Loaded Micelles Suppresses Allergic Inflammation.

    PubMed

    Peng, Xia; Wang, Juan; Li, Xianyang; Lin, Lihui; Xie, Guogang; Cui, Zelin; Li, Jia; Wang, Yuping; Li, Li

    2015-12-01

    Mast cells and basophils are effector cells in the pathophysiology of allergic diseases. Targeted elimination of these cells may be a promising strategy for the treatment of allergic disorders. Our present study aims at targeted delivery of anti-FcεRIα Fab-conjugated celastrol-loaded micelles toward FcεRIα receptors expressed on mast cells and basophils to have enhanced anti-allergic effect. To achieve this aim, we prepared celastrol-loaded (PEO-block-PPO-block-PEO, Pluronic) polymeric nanomicelles using thin-film hydration method. The anti-FcεRIα Fab Fragment was then conjugated to carboxyl groups on drug-loaded micelles via EDC amidation reaction. The anti-FcεRIα Fab-conjugated celastrol-loaded micelles revealed uniform particle size (93.43 ± 12.93 nm) with high loading percentage (21.2 ± 1.5% w/w). The image of micelles showed oval and rod like. The anti-FcεRIα Fab-conjugated micelles demonstrated enhanced cellular uptake and cytotoxity toward target KU812 cells than non-conjugated micelles in vitro. Furthermore, diffusion of the drug into the cells allowed an efficient induction of cell apoptosis. In mouse model of allergic asthma, treatment with anti-FcεRIα Fab-conjugated micelles increased lung accumulation of micelles, and significantly reduced OVA-sIgE, histamine and Th2 cytokines (IL-4, IL-5, TNF-α) levels, eosinophils infiltration and mucus production. In addition, in mouse model of passive cutaneous anaphylaxis, anti-FcεRIα Fab-conjugated celastrol-loaded micelles treatment significantly decreased extravasated evan's in the ear. These results indicate that anti-FcεRIα Fab-conjugated celastrol-loaded micelles can target and selectively kill mast cells and basophils which express FcεRIα, and may be efficient reagents for the treatment of allergic disorders and mast cell related diseases.

  1. All Trans Retinoic Acid, Transforming Growth Factor β and Prostaglandin E2 in Mouse Plasma Synergize with Basophil-Secreted Interleukin-4 to M2 Polarize Murine Macrophages

    PubMed Central

    Elisia, Ingrid; Lam, Vivian; Hsu, Brian E.; Lai, June; Luk, Beryl; Samudio, Ismael; Krystal, Gerald

    2016-01-01

    In previous studies we found that macrophages (MФs) from SH2-containing inositol-5′-phosphatase (SHIP) deficient mice are M2 polarized while their wild type (WT) counterparts are M1 polarized and that this difference in MФ phenotype can be recapitulated during in vitro derivation from bone marrow if mouse plasma (MP), but not fetal calf serum, is added to standard M-CSF-containing cultures. In the current study we investigated the mechanism by which MP skews SHIP-/- but not +/+ MФs to an M2 phenotype. Our results suggest that SHIP-/- basophils constitutively secrete higher levels of IL-4 than SHIP+/+ basophils and this higher level of IL-4 is sufficient to skew both SHIP+/+ and SHIP-/- MФs to an M2 phenotype, but only when MP is present to increase the sensitivity of the MФs to this level of IL-4. MP increases the IL-4 sensitivity of both SHIP+/+ and -/- MФs not by increasing cell surface IL-4 or CD36 receptor levels, but by triggering the activation of Erk and Akt and the production of ROS, all of which play a critical role in sensitizing MФs to IL-4-induced M2 skewing. Studies to identify the factor(s) in MP responsible for promoting IL-4-induced M2 skewing suggests that all-trans retinoic acid (ATRA), TGFβ and prostaglandin E2 (PGE2) all play a role. Taken together, these results indicate that basophil-secreted IL-4 plays an essential role in M2 skewing and that ATRA, TGFβ and PGE2 within MP collaborate to dramatically promote M2 skewing by acting directly on MФs to increase their sensitivity to IL-4. PMID:27977740

  2. Differences in IgE mediated basophil degranulation induced by proteic fractions from whole flea body extract in patients with papular urticaria by flea bite and healthy controls

    PubMed Central

    2013-01-01

    Background Papular urticaria by flea bite (PUFB) is a chronic inflammatory disease in children. The aim of this study was to assess the functional activity of IgE to protein fractions from flea body extract, through basophil degranulation in PUFB patients and controls. Methods Basophil degranulation, measured by overexpression of CD63 surface molecules, was evaluated by flow cytometry in samples from patients and controls. Cell stimulation was performed with three fractions with different molecular weight from flea body extract using a Basotest® modified protocol. Mann–Whitney U-test was used for comparisons. Results Specific IgE from PUFB patients and healthy controls induced basophil degranulation to flea body extract with no significant differences between them (16.2 ± 3.1% vs 13.6 ± 2.8% p = 0.77). However, when flea extract was analyzed in fractions with proteins ranging different molecular weights, significant differences were observed on the response from patients compared with controls to <50 kD (14.9 ± 5.1% vs 9.7 ± 2.1% p = 0.0058) and 50–100 kD proteic fractions (8.3 ± 3.2% vs 2.8 ± 1.6% p = 0.0021). Conclusion In this study, was established that the differential response by IgE, in PUFB, depends from the molecular weight of the antigens contained in the flea extract. These antigens may be related to 30–35 kD proteins previously described as major allergens. PMID:23680530

  3. Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-09-09

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult L1 Acute Lymphoblastic Leukemia; Adult L2 Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  4. Treatment of chronic lymphocytic leukemia.

    PubMed

    Ferrajoli, Alessandra; O'Brien, Susan M

    2004-04-01

    Treatment options for patients with chronic lymphocytic leukemia have changed over the past two decades. This article reviews the experience accumulated with the use of alkylating agents alone and in combination; purine analogues alone and in combination and monoclonal antibodies such as rituximab, and alemtuzumab alone and in combination. The results obtained with different treatment strategies are summarized, compared, and reviewed.

  5. Immunoregulatory properties of childhood leukemias

    SciTech Connect

    Banker, D.S.; Pahwa, R.N.; Miller, D.R.; Hilgartner, M.W.; Good, R.A.; Pahwa, S.G.

    1982-07-01

    Investigation of in vitro humoral immune responses and immunoregulatory properties of leukemic cell was carried out in 17 children with acute leukemia prior to therapy. Leukemias were of the non-T, non-B-cell type in 13 patients and of T-cell origin in four. Bone marrow and peripheral blood cells consisted of 24-96% lymphoblasts and were generally deficient in surface Ig-positive cells. Induction of Ig secreting cells in response to pokeweed mitogen was markedly decreased in marrow and peripheral mononuclear cell cultures of leukemic patients. Co-culture of leukemic cells with normal lymphocytes led to marked deviations from the expected Ig secreting-cell response of the cell mixtures. The predominant effect was enhancement, as was the case with eight non-T, non-B-cell and one T-cell leukemia samples. Suppression of the Ig secreting-cell response was observed in only three instances, two with non-T, non-B-cell and one with T-cell leukemia samples. These findings implicate non-T, non-B as well as more differentiated leukemic cells in having the potential for modifying Ig production by B cells.

  6. Abrupt evolution of Philadelphia chromosome-positive acute myeloid leukemia in myelodysplastic syndrome.

    PubMed

    Fukunaga, Akiko; Sakoda, Hiroto; Iwamoto, Yoshihiro; Inano, Shojiro; Sueki, Yuki; Yanagida, Soshi; Arima, Nobuyoshi

    2013-03-01

    Myelodysplastic syndrome (MDS) is a clonal disorder arising from an alteration in multipotent stem cells, which lose the ability of normal proliferation and differentiation. Disease progression occurs in approximately 30% MDS cases. Specific chromosomal alterations seem responsible for each step in the evolution of acute myeloid leukemia (AML). Multiple genetic aberrations occur during the clonal evolution of MDS; however, few studies report the presence of the Philadelphia (Ph) chromosome. We report a rare case of Ph-positive AML, which evolved during the course of low-risk MDS. The patient, a 76-year-old man with mild leukocytopenia, was diagnosed with MDS, refractory neutropenia (RN). After 1.5 yr, his peripheral blood and bone marrow were suddenly occupied by immature basophils and myeloblasts, indicating the onset of AML. A bone marrow smear showed multilineage dysplasia, consistent with MDS evolution. Chromosomal analysis showed an additional t(9;22)(q34;q11) translocation. Because progression occurred concurrently with emergence of the Ph chromosome, we diagnosed this case as Ph-positive AML with basophilia arising from the clonal evolution of MDS. The patient was initially treated with nilotinib. A hematological response was soon achieved with disappearance of the Ph chromosome in the bone marrow. Emergence of Ph-positive AML in the course of low-risk MDS has rarely been reported. We report this case as a rare clinical course of MDS.

  7. Cannabis Extract Treatment for Terminal Acute Lymphoblastic Leukemia with a Philadelphia Chromosome Mutation

    PubMed Central

    Singh, Yadvinder; Bali, Chamandeep

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells and is typically well treated with combination chemotherapy, with a remission state after 5 years of 94% in children and 30–40% in adults. To establish how aggressive the disease is, further chromosome testing is required to determine whether the cancer is myeloblastic and involves neutrophils, eosinophils or basophils, or lymphoblastic involving B or T lymphocytes. This case study is on a 14-year-old patient diagnosed with a very aggressive form of ALL (positive for the Philadelphia chromosome mutation). A standard bone marrow transplant, aggressive chemotherapy and radiation therapy were revoked, with treatment being deemed a failure after 34 months. Without any other solutions provided by conventional approaches aside from palliation, the family administered cannabinoid extracts orally to the patient. Cannabinoid resin extract is used as an effective treatment for ALL with a positive Philadelphia chromosome mutation and indications of dose-dependent disease control. The clinical observation in this study revealed a rapid dose-dependent correlation. PMID:24474921

  8. Cannabis extract treatment for terminal acute lymphoblastic leukemia with a Philadelphia chromosome mutation.

    PubMed

    Singh, Yadvinder; Bali, Chamandeep

    2013-09-01

    Acute lymphoblastic leukemia (ALL) is a cancer of the white blood cells and is typically well treated with combination chemotherapy, with a remission state after 5 years of 94% in children and 30-40% in adults. To establish how aggressive the disease is, further chromosome testing is required to determine whether the cancer is myeloblastic and involves neutrophils, eosinophils or basophils, or lymphoblastic involving B or T lymphocytes. This case study is on a 14-year-old patient diagnosed with a very aggressive form of ALL (positive for the Philadelphia chromosome mutation). A standard bone marrow transplant, aggressive chemotherapy and radiation therapy were revoked, with treatment being deemed a failure after 34 months. Without any other solutions provided by conventional approaches aside from palliation, the family administered cannabinoid extracts orally to the patient. Cannabinoid resin extract is used as an effective treatment for ALL with a positive Philadelphia chromosome mutation and indications of dose-dependent disease control. The clinical observation in this study revealed a rapid dose-dependent correlation.

  9. An assessment of the clinicohematological criteria for the accelerated phase of chronic myeloid leukemia.

    PubMed

    Cervantes, F; López-Guillermo, A; Bosch, F; Terol, M J; Rozman, C; Montserrat, E

    1996-10-01

    In order to assess the relative importance of the clinicohematological features most commonly associated with the accelerated phase (AP) of chronic myeloid leukemia (CML) in 175 consecutive patients, 12 variables generally considered as indicating AP were analyzed for their predictive value for blast crisis (BC) appearance in less than 1 yr. At the time of analysis, 118 patients had died and 104 had developed BC. At univariate study, 6 features were associated with a significantly higher BC-probability: poor performance status (ECOG score > or = 2), unexplained fever/sweats, severe bone pain, progressive splenomegaly despite adequate therapy, blood basophils (> or = 20%) and peripheral blasts (6-12%). At logistic regression, only bone pain and blood blasts (6-12%) retained their prognostic importance; the relative risk of unexplained fever/sweats and progressive splenomegaly was also clinically relevant. One-year BC-probability from the appearance of 1 or more of the above features was 77.3% (95% CI: 66-86.6) and 100% since all 4 were observed. Finally, at least 1 of the 4 features was present prior to death in 6 of 7 patients dying from CML-related causes while not in BC. AP can be defined by the appearance along CML evolution of 1 or more of the 4 above-mentioned clinicohematological features.

  10. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  11. Mouse models for core binding factor leukemia.

    PubMed

    Chin, D W L; Watanabe-Okochi, N; Wang, C Q; Tergaonkar, V; Osato, M

    2015-10-01

    RUNX1 and CBFB are among the most frequently mutated genes in human leukemias. Genetic alterations such as chromosomal translocations, copy number variations and point mutations have been widely reported to result in the malfunction of RUNX transcription factors. Leukemias arising from such alterations in RUNX family genes are collectively termed core binding factor (CBF) leukemias. Although adult CBF leukemias generally are considered a favorable risk group as compared with other forms of acute myeloid leukemia, the 5-year survival rate remains low. An improved understanding of the molecular mechanism for CBF leukemia is imperative to uncover novel treatment options. Over the years, retroviral transduction-transplantation assays and transgenic, knockin and knockout mouse models alone or in combination with mutagenesis have been used to study the roles of RUNX alterations in leukemogenesis. Although successful in inducing leukemia, the existing assays and models possess many inherent limitations. A CBF leukemia model which induces leukemia with complete penetrance and short latency would be ideal as a platform for drug discovery. Here, we summarize the currently available mouse models which have been utilized to study CBF leukemias, discuss the advantages and limitations of individual experimental systems, and propose suggestions for improvements of mouse models.

  12. Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2017-09-06

    B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  13. Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Acute Myelomonocytic Leukemia (M4)

  14. Vosaroxin and Infusional Cytarabine in Treating Patients With Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-04-05

    Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia With Multilineage Dysplasia; Myeloid Sarcoma; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia; Therapy-Related Myelodysplastic Syndrome

  15. 3-AP and Fludarabine in Treating Patients With Myeloproliferative Disorders, Chronic Myelomonocytic Leukemia, or Accelerated Phase or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-16

    Accelerated Phase Chronic Myelogenous Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Philadelphia Chromosome Negative Chronic Myelogenous Leukemia; Polycythemia Vera; Primary Myelofibrosis; Relapsing Chronic Myelogenous Leukemia

  16. Genetics Home Reference: core binding factor acute myeloid leukemia

    MedlinePlus

    ... acute myeloid leukemia core binding factor acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... collapse boxes. Description Core binding factor acute myeloid leukemia (CBF-AML) is one form of a cancer ...

  17. Genetics Home Reference: cytogenetically normal acute myeloid leukemia

    MedlinePlus

    ... normal acute myeloid leukemia cytogenetically normal acute myeloid leukemia Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Cytogenetically normal acute myeloid leukemia (CN-AML) is one form of a cancer ...

  18. Chronic B-Cell Leukemias and Agent Orange

    MedlinePlus

    ... here Enter ZIP code here Chronic B-cell Leukemias and Agent Orange Veterans who develop chronic B- ... care and disability compensation. About chronic B-cell leukemias Leukemia is a cancer of the blood cells. ...

  19. Chronic B-Cell Leukemias and Agent Orange

    MedlinePlus

    ... here Enter ZIP code here Chronic B-cell Leukemias and Agent Orange Veterans who develop chronic B- ... care and disability compensation. About chronic B-cell leukemias Leukemia is a cancer of the blood cells. ...

  20. What's New in Chronic Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Myeloid Leukemia (CML) About Chronic Myeloid Leukemia What's New in Chronic Myeloid Leukemia Research and Treatment? Studies ... such as cyclosporine or hydroxychloroquine, with a TKI. New drugs for CML Because researchers now know the ...

  1. What's New in Adult Acute Myeloid Leukemia Research and Treatment?

    MedlinePlus

    ... Leukemia (AML) About Acute Myeloid Leukemia (AML) What’s New in Acute Myeloid Leukemia Research and Treatment? Researchers ... benefit from current treatments. Researchers are studying many new chemo drugs for use in AML, including: Sapacitabine, ...

  2. What Are the Key Statistics about Acute Myeloid Leukemia?

    MedlinePlus

    ... Acute Myeloid Leukemia (AML) What Are the Key Statistics About Acute Myeloid Leukemia? The American Cancer Society’s ... myeloid leukemia . Visit the American Cancer Society’s Cancer Statistics Center for more key statistics. Written by References ...

  3. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  4. Mutational landscape, clonal evolution patterns, and role of RAS mutations in relapsed acute lymphoblastic leukemia

    PubMed Central

    Oshima, Koichi; Khiabanian, Hossein; da Silva-Almeida, Ana C.; Tzoneva, Gannie; Abate, Francesco; Ambesi-Impiombato, Alberto; Sanchez-Martin, Marta; Carpenter, Zachary; Penson, Alex; Perez-Garcia, Arianne; Eckert, Cornelia; Nicolas, Concepción; Balbin, Milagros; Sulis, Maria Luisa; Kato, Motohiro; Koh, Katsuyoshi; Paganin, Maddalena; Basso, Giuseppe; Gastier-Foster, Julie M.; Devidas, Meenakshi; Loh, Mignon L.; Kirschner-Schwabe, Renate; Palomero, Teresa; Rabadan, Raul; Ferrando, Adolfo A.

    2016-01-01

    Although multiagent combination chemotherapy is curative in a significant fraction of childhood acute lymphoblastic leukemia (ALL) patients, 20% of cases relapse and most die because of chemorefractory disease. Here we used whole-exome and whole-genome sequencing to analyze the mutational landscape at relapse in pediatric ALL cases. These analyses identified numerous relapse-associated mutated genes intertwined in chemotherapy resistance-related protein complexes. In this context, RAS-MAPK pathway-activating mutations in the neuroblastoma RAS viral oncogene homolog (NRAS), kirsten rat sarcoma viral oncogene homolog (KRAS), and protein tyrosine phosphatase, nonreceptor type 11 (PTPN11) genes were present in 24 of 55 (44%) cases in our series. Interestingly, some leukemias showed retention or emergence of RAS mutant clones at relapse, whereas in others RAS mutant clones present at diagnosis were replaced by RAS wild-type populations, supporting a role for both positive and negative selection evolutionary pressures in clonal evolution of RAS-mutant leukemia. Consistently, functional dissection of mouse and human wild-type and mutant RAS isogenic leukemia cells demonstrated induction of methotrexate resistance but also improved the response to vincristine in mutant RAS-expressing lymphoblasts. These results highlight the central role of chemotherapy-driven selection as a central mechanism of leukemia clonal evolution in relapsed ALL, and demonstrate a previously unrecognized dual role of RAS mutations as drivers of both sensitivity and resistance to chemotherapy. PMID:27655895

  5. Nonsteroidal anti-inflammatory drugs enhance IgE-mediated activation of human basophils in patients with food anaphylaxis dependent on and independent of nonsteroidal anti-inflammatory drugs.

    PubMed

    Pascal, M; Muñoz-Cano, R; Milà, J; Sanz, M L; Diaz-Perales, A; Sánchez-López, J; García-Moral, A; Juan, M; Valero, A; Yagüe, J; Picado, C; Bartra, J

    2016-08-01

    Nonsteroidal anti-inflammatory drugs (NSAIDs) act as cofactors worsening the allergic reactions induced by food allergens. The aim of this study was to evaluate the effect of both lysine acetylsalicylate (L-ASA) (non-selective cyclooxygenase (COX) inhibitor) and valdecoxib (selective COX-2 inhibitor) in basophils activated by peach lipid transfer protein (Pru p 3) in patients with food-dependent NSAID-induced anaphylaxis (FDNIA). Twenty Pru p 3-allergic patients with FDNIA group, eleven peach anaphylaxis not exacerbated by NSAIDs (no-NSAID group) and 5 healthy volunteers were recruited. Basophil activation (BA) was measured as expression of CD63 (Flow(2) CAST(™) ; Bühlmann(®) ), after stimulation with Pru p 3, both alone and in combination with L-ASA (1.13, 3.38 and 6.78 mm) or valdecoxib (0.87, 7.8 and 31.25 μm). Basophils from no-NSAID group were significantly more reactive and sensitive to Pru p 3 than those from the FDNIA group. In both groups, an increase in BA was observed when basophils were exposed to Pru p 3 and L-ASA. In the FDNIA group, valdecoxib partially terminates the BA induced by Pru p 3, whereas in the no-NSAID group, a dual effect was observed depending on the concentration tested. This study indicates that subjects with food-induced anaphylaxis differ from FDNIA subjects in the higher reactivity and sensitivity of their basophils to allergen challenge. We have shown a direct effect of NSAIDs on basophils using a human model of FDNIA. Our results also suggest that selective COX2 inhibitors might be a safe alternative. BA test may be a useful tool in the study of the pathogenic mechanism of the cofactor phenomenon. © 2016 John Wiley & Sons Ltd.

  6. Azacitidine With or Without Entinostat in Treating Patients With Myelodysplastic Syndromes, Chronic Myelomonocytic Leukemia, or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-12-08

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  7. Diagnosis of Large Granular Lymphocytic Leukemia in a Patient Previously Treated for Acute Myeloblastic Leukemia

    PubMed Central

    Bozdag, Sinem Civriz; Namdaroglu, Sinem; Kayikci, Omur; Kaygusuz, Gülsah; Demiriz, Itir; Cinarsoy, Murat; Tekgunduz, Emre; Altuntas, Fevzi

    2013-01-01

    Large granular lymphocytic (LGL) leukemia is a lymphoproliferative disease characterized by the clonal expansion of cytotoxic T or natural killer cells. We report on a patient diagnosed with T-cell LGL leukemia two years after the achievement of hematologic remission for acute myeloblastic leukemia. PMID:24416499

  8. [Oncogenes and the origin of leukemia. Acute avian leukemia viruses].

    PubMed

    Graf, T

    1988-03-01

    Oncogenes have been intimately associated with the genesis of human neoplasms. A particularly useful system to study the mechanism of tumorigenesis is a small group of avian retroviruses that carry two oncogenes. These viruses causes acute leukemias and can transform hematopoietic cells in vitro. The mechanisms by which viral oncogenes affect the growth control and differentiation of their target cells is now understood in fair detail for two of these virus strains. In the avian erythroblastosis virus AEV, the v-erbB oncogene deregulates the growth control of erythroid precursors, while verbA blocks their terminal differentiation into erythrocytes. Based on the findings that v-erbB oncogene corresponds to a mutated growth factor receptor gene and that v-erbA corresponds to a mutated hormone receptor gene, models have been developed that explain the function of these two oncogenes on a molecular basis. The myelomonocytic leukemia virus MH2 acts by a completely different mechanism. In this case, the v-myc oncogene stimulates the proliferation of macrophage-like cells, while the v-mil gene stimulates them to produce their own growth factor, thus leading to autocrine growth. It will be interesting to determine whether the type of mechanisms of oncogene cooperativity elucidated for acute leukemia viruses are also operative during leukemogenesis in humans.

  9. A comparison between two different in vitro basophil activation tests for gluten- and cow's milk protein sensitivity in irritable bowel syndrome (IBS)-like patients.

    PubMed

    Carroccio, Antonio; Brusca, Ignazio; Mansueto, Pasquale; D'alcamo, Alberto; Barrale, Maria; Soresi, Maurizio; Seidita, Aurelio; La Chiusa, Stella M; Iacono, Giuseppe; Sprini, Delia

    2013-06-01

    The diagnosis of food hypersensitivity (FH) in adult patients with gastrointestinal symptoms, beyond the immediate IgE-mediated clinical manifestations, is very often difficult. The aims of our study were to: 1) evaluate the frequency of FH in patients with irritable bowel syndrome (IBS)-like clinical presentation; and 2) compare the diagnostic accuracy of two different methods of in vitro basophil activation tests. Three hundred and five patients (235 females, age range 18-66 years) were included and underwent a diagnostic elimination diet and successive double-blind placebo-controlled (DBPC) challenges. Two different methods of in vitro basophil activation tests (BAT) (CD63 expression after in vitro wheat or cow's milk proteins stimulation) were evaluated: one was performed on separated leukocytes, and the other on whole blood. Ninety patients of the 305 studied (29.5%) were positive to the challenges and were diagnosed as suffering from FH. BAT on separate leukocytes showed a sensitivity of 86% and a specificity of 91% in FH diagnosis. BAT on whole blood showed a sensitivity of 15%-20% and a specificity of 73% in FH diagnosis (p<0.0001 compared to the other method). About one third of the IBS patients included in the study were suffering from FH and were cured on the elimination diet. The BAT based on CD63 detection on whole blood samples did not work in FH diagnosis and showed a significantly lower sensitivity, specificity and diagnostic accuracy than the assay based on separated leukocytes.

  10. General Approach to Treatment of Chronic Myelomonocytic Leukemia

    MedlinePlus

    ... Growth Factors for Treating Chronic Myelomonocytic Leukemia Radiation Therapy for Chronic Myelomonocytic Leukemia Surgery for Chronic Myelomonocytic ... Cancer Information Cancer Prevention & Detection Cancer Basics ...

  11. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  12. Tipifarnib in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-02-01

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. Transplantation in chronic lymphocytic leukemia.

    PubMed

    Le Dieu, Rifca; Gribben, John G

    2007-02-01

    Although there have been no randomized trials comparing the outcome of stem cell transplantation (SCT) with standard chemotherapy for patients with chronic lymphocytic leukemia (CLL), increasingly, both autologous and allogeneic SCT approaches are being explored in this disease. Clinical trials have demonstrated that these approaches are feasible, but current data suggest that autologous transplantation is not curative and myeloablative SCT, although offering the potential for cure, is associated with high treatment-related mortality. There is a clear demonstration of a graft-versus-leukemia effect in CLL, with encouraging results seen after SCT with reduced-intensity conditioning. Because no other treatment modalities are currently capable of improving survival in this disease, the treatment of choice for younger patients with poor-risk CLL may well be SCT, but continued enrollment of appropriate patients into well-designed clinical trials is vital to compare advances in SCT with the advances occurring in chemoimmunotherapy in CLL.

  14. Lenalidomide and Vaccine Therapy in Treating Patients With Early-Stage Asymptomatic Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma

    ClinicalTrials.gov

    2017-04-24

    Chronic Lymphocytic Leukemia; Stage 0 Chronic Lymphocytic Leukemia; Stage I Chronic Lymphocytic Leukemia; Stage I Small Lymphocytic Lymphoma; Stage II Chronic Lymphocytic Leukemia; Stage II Small Lymphocytic Lymphoma

  15. Selective T-Cell Depletion to Reduce GVHD (Patients) Receiving Stem Cell Tx to Treat Leukemia, Lymphoma or MDS

    ClinicalTrials.gov

    2016-09-21

    Graft vs Host Disease; Myelodysplastic Syndromes; Leukemia; Leukemia, Myeloid; Leukemia, Myelomonocytic, Chronic; Leukemia, Lymphocytic; Lymphoma; Lymphoma, Mantle-cell; Lymphoma, Non-Hodgkin; Hodgkin Disease

  16. Redefining transplant in acute leukemia.

    PubMed

    Sellar, Rob; Goldstone, Anthony H; Lazarus, Hillard M

    2011-12-01

    Assigning the correct treatment to those with acute leukemia is challenging and requires careful assessment of both the disease and the patient. Our ability to assign relapse risk to disease is evolving and incorporates cytogenetics, molecular lesions, and assessment of minimal residual disease after initial treatment. Allogeneic hematopoietic progenitor cell transplantation (alloHCPT) is one of the most efficacious treatments available to the physician. In adult acute lymphoblastic leukemia (ALL) despite the treatment risk, patients with a matched sibling who achieve CR should be referred for transplant. Prospective trials investigating the role of unrelated donors are in progress. There is little prospective evidence, but nonetheless encouraging data, to support referring older patients for alloHPCT using reduced intensity conditioning (RIC) regimens. In acute myeloid leukemia (AML), all high-risk patients and the majority of intermediate-risk patients with a matched sibling should be offered alloHPCT in CR1. In addition there is evidence that some patients previously assigned as good-risk would benefit from sibling transplant. Use of unrelated donors will expand the numbers eligible for transplant and should be considered when a matched-sibling is not available particularly in high-risk patients. Similarly to ALL, the use of RIC is allowing transplantation to be offered to those deemed too old or unfit for myeloablative conditioning. The importance of enrolling patients into suitable prospective clinical trials cannot be overstated.

  17. Epidemiology of acute lymphoblastic leukemia

    SciTech Connect

    Pendergrass, T.W.

    1985-06-01

    Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury.

  18. [Leukemia research in Germany: the Competence Network Acute and Chronic Leukemias].

    PubMed

    Kossak-Roth, Ute; Saußele, Susanne; Aul, Carlo; Büchner, Thomas; Döhner, Hartmut; Dugas, Martin; Ehninger, Gerhard; Ganser, Arnold; Giagounidis, Aristoteles; Gökbuget, Nicola; Griesshammer, Martin; Hasford, Jörg; Heuser, Michael; Hiddemann, Wolfgang; Hochhaus, Andreas; Hoelzer, Dieter; Niederwieser, Dietger; Reiter, Andreas; Röllig, Christoph; Hehlmann, Rüdiger

    2016-04-01

    The Competence Network "Acute and Chronic Leukemias" was founded in 1997 by the consolidation of the leading leukemia study groups in Germany. Key results are the development of new trials and cooperative studies, the setup of patient registries and biobanking facilities, as well as the improvement of study infrastructure. In 2003, the concept of the competence network contributed to the foundation of the European LeukemiaNet (ELN). Synergy with the ELN resulted in cooperation on a European and international level, standardization of diagnostics and treatment, and recommendations for each leukemia and interdisciplinary specialty. The ultimate goal of the network is the cure of leukemia through cooperative research.

  19. Defining leukemia stem cells in MLL-translocated leukemias: implications for novel therapeutic strategies.

    PubMed

    Faber, J; Armstrong, S A

    2007-01-01

    Hematological malignancies and probably many other tumors are dependent on highly proliferating and self-renewing cancer stem cells. An important question in the development of novel, less toxic antileukemic strategies specifically targeting leukemia stem cells is how closely leukemia stem cells are related to normal hematopoietic stem cells. It has been recently demonstrated that leukemia stem cells can be derived from different stages in normal hematopoiesis and have unique phenotypic and genetic features. Introduction of Mixed-lineage leukemia ( MLL)-fusion oncoproteins, frequently found in infant leukemias and therapy-related leukemias, into differentiated hematopoietic progenitor cells results in the generation of leukemias with a high frequency of leukemia stem cells. The progenitor-derived leukemia stem cells ectopically express a limited stem cell program while maintaining the global identity of differentiated myeloid cells. Development of therapeutic strategies that specifically target the leukemia stem cell program while sparing normal hematopoietic stem cells may represent a novel therapeutic approach in human leukemias with high efficacy yet less side effects.

  20. In vitro γ Irradiation of Leukemic Cells in Mice, Rats, and Guinea Pigs

    NASA Astrophysics Data System (ADS)

    Gross, Ludwik; Dreyfuss, Yolande; Ehrenreich, Theodore; Feldman, Dorothy; Limbert, Lorraine M.

    1980-12-01

    In vitro γ irradiation of virus-induced (Gross) mouse leukemia cells at doses of 350-1600 rads (1 rad = 0.01 gray) had no effect on their ability to induce leukemia, usually within 2 weeks, after transplantation into syngeneic mice. However, when cells irradiated at doses of 2000-20,000 rads were transplanted, they induced leukemia after a latency period exceeding 2.5 months, similar to the result observed in mice inoculated with filtered mouse leukemia extracts. Similar results were also obtained after irradiation of leukemic cells derived from rats in which leukemia had been induced by rat-adapted mouse leukemia virus. Apparently, γ irradiation at a dose of, or exceeding, 2000 rads, inhibits the ability of mouse and rat leukemic cells to induce leukemia after transplantation into syngeneic hosts; however, it does not inactivate the virus carried by such cells nor prevent it from inducing leukemia. [In previous experiments, doses of more than 4,500,000 rads were needed to inactivate the passage A (Gross) leukemia virus carried in either mouse or rat leukemic cells.] In vitro γ irradiation of L2C guinea pig leukemic cells at doses of 750--2500 rads had no apparent effect on their ability to induce leukemia after transplantation into strain 2 guinea pigs. However, irradiation at doses of 3250-20,000 rads inactivated their ability to do so. The morphology of mouse, rat, and guinea pig leukemic cells and the virus particles present in such cells was not affected by irradiation at doses of 20,000 rads.

  1. Clofarabine and Melphalan Before Donor Stem Cell Transplant in Treating Patients With Myelodysplasia, Acute Leukemia in Remission, or Chronic Myelomonocytic Leukemia

    ClinicalTrials.gov

    2017-07-13

    Adult Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia in Remission; Myelodysplastic Syndrome; Secondary Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Therapy-Related Myelodysplastic Syndrome

  2. Eosinophilia in a cat with acute leukemia

    PubMed Central

    Gilroy, Cornelia; Forzán, María; Drew, Anne; Vernau, William

    2011-01-01

    A 4-year-old castrated male domestic shorthaired cat with a history of vomiting and anorexia was diagnosed with leukemia with marked hepatic and splenic infiltration and concurrent eosinophilia with marked tissue infiltration. Despite thorough immunocytochemical and immunohistochemical immunophenotyping, the cell lineage of the leukemia was not identified. PMID:22379202

  3. Genetic instability in inherited and sporadic leukemias.

    PubMed

    Popp, Henning D; Bohlander, Stefan K

    2010-12-01

    Genetic instability due to increased DNA damage and altered DNA repair is of central significance in the initiation and progression of inherited and sporadic human leukemias. Although very rare, some inherited DNA repair insufficiency syndromes (e.g., Fanconi anemia, Bloom's syndrome) have added substantially to our understanding of crucial mechanisms of leukemogenesis in recent years. Conversely, sporadic leukemias account for the main proportion of leukemias and here DNA damaging reactive oxygen species (ROS) play a central role. Although the exact mechanisms of increased ROS production remain largely unknown and no single pathway has been detected thus far, some oncogenic proteins (e.g., the activated tyrosine kinases BCR-ABL1 and FLT3-ITD) seem to play a key role in driving genetic instability by increased ROS generation which influences the disease course (e.g., blast crisis in chronic myeloid leukemia or relapse in FLT3-ITD positive acute myeloid leukemia). Of course other mechanisms, which promote genetic instability in leukemia also exist. A newly emerging mechanism is the genome-wide alteration of epigenetic marks (e.g., hypomethylation of histone H3K79), which promotes chromosomal instability. Taken together genetic instability plays a critical role both in inherited and sporadic leukemias and emerges as a common theme in both inherited and sporadic leukemias. Beyond its theoretical impact, the analysis of genetic instability may lead the way to the development of innovative therapy strategies. © 2010 Wiley-Liss, Inc.

  4. SnapShot: chronic lymphocytic leukemia.

    PubMed

    Ciccone, Maria; Ferrajoli, Alessandra; Keating, Michael J; Calin, George A

    2014-11-10

    Chronic lymphocytic leukemia (CLL) is the most common leukemia among adults in western countries. This SnapShot depicts the origins and evolution of this B cell malignancy, describes prognostic factors and CLL animal models, and illustrates therapies in preclinical and clinical development against CLL.

  5. Eosinophilia in a cat with acute leukemia.

    PubMed

    Gilroy, Cornelia; Forzán, María; Drew, Anne; Vernau, William

    2011-09-01

    A 4-year-old castrated male domestic shorthaired cat with a history of vomiting and anorexia was diagnosed with leukemia with marked hepatic and splenic infiltration and concurrent eosinophilia with marked tissue infiltration. Despite thorough immunocytochemical and immunohistochemical immunophenotyping, the cell lineage of the leukemia was not identified.

  6. Comparative effect of recombinant IL-1, -2, -3, -4, and -6, IFN-gamma, granulocyte-macrophage-colony-stimulating factor, tumor necrosis factor-alpha, and histamine-releasing factors on the secretion of histamine from basophils

    SciTech Connect

    Alam, R.; Welter, J.B.; Forsythe, P.A.; Lett-Brown, M.A.; Grant, J.A. )

    1989-05-15

    Most cytokines possess multiple biologic activities. This study was undertaken to investigate the effect of rIL-1 beta, -2, -3, -4 and -6, IFN-gamma, TNF-alpha, and granulocyte-macrophage (GM)-CSF on basophils from 16 donors and the amount of histamine released was compared with that by partially purified mononuclear cell-derived histamine-releasing factor (HRF) and anti-IgE. We found that only IL-3 and GM-CSF at relatively high doses (50 to 500 ng/ml) released small amounts of histamine (3 to 14%) from two allergic donors. In contrast, both HRF and anti-IgE released significant amounts of histamine from all donors. Other cytokines did not release any measurable quantity of histamine. Simultaneous addition of several cytokines to the basophils also failed to release histamine. IL-3, GM-CSF, and IL-1 can also release histamine at lower concentrations (less than 5 ng/ml) when incubated with basophils in the presence of D{sub 2}O. Basophils from 6 out of 13 allergic donors released histamine in response to IL-3, whereas three donors responded to IL-1 beta and two responded to GM-CSF. The results of this study demonstrated that although IL-3 and GM-CSF release small amounts of histamine only from a select group of allergic patients, mononuclear cell-derived HRF is more potent in their action and release histamine from normals as well as allergic patients.

  7. Acute Appendicitis in Patients with Acute Leukemia

    PubMed Central

    Kim, Ki Up; Kim, Jin Kyeung; Won, Jong Ho; Hong, Dae Sik; Park, Hee Sook; Park, Kyeung Kyu

    1993-01-01

    The decision to operate for abdominal pain in patients with leukopenia can be exceedingly difficult. Surgical exploration may be the only effective way to differentiate acute appendicitis from other causes, but it involves considerable risk of infectious complications due to immunesuppression. Leukemic patients, who presented significant RLQ pain, had been indicated for operation, despite having advanced disease or having had received chemotherapy or steroids. Four adult leukemia patients, complicated by acute appendictis, were reviewed. Two patients were in induction chemotherapy, one receiving salvage chemotheapy due to relapse and the other was in conservative treatment. Two patients were acute myelocytic leukemia (AML), one had acute lymphocytic leukemia (ALL), and the other had aleukemic leukemia. All patients underwent appendectomy and recovered without complication. Our experience supports the theory that the surgical management of appendicitis in acute leukemia is the most effective way, in spite of leukopenia. PMID:8268146

  8. Childhood acute leukemia and intestinal parasitosis.

    PubMed

    Rivera-Luna, R; Cárdenas-Cardos, R; Martínez-Guerra, G; Ayón, A; Leal, C; Rivera-Ortegón, F

    1989-11-01

    Infectious complications are the leading cause of mortality in children with acute leukemia. Despite the fact that intestinal parasitosis is a rather frequent finding and a health problem in underdeveloped countries, in our experience the incidence of helminthic and protozoan infections among children with leukemia is uncommon. We analyzed 54 consecutive patients with leukemia in a period of 5 years, and only seven (12.9%) had intestinal parasites, four of whom died because of the infection or complication by the parasites. One hundred children without any malignancy were the control group, 26 (26%) of whom had intestinal parasitosis. When we compared the frequency of parasitosis in the control group with the children with leukemia and parasitosis, we found a statistical difference (p less than 0.05). We speculate that parasitic infections may reduce the risk of childhood leukemia.

  9. [Respiratory distress syndrome due to hyperleukocytic leukemias].

    PubMed

    Valdovinos Mahave, M C; Salvador Osuna, C; del Agua, C; Lanau Arilla, M P; Vicente Cámara, M P

    1999-07-01

    Hyperleukocytic leukemias are a small proportion of leukemias that have white blood cell count > 100 x 10(9)/l, most of them are leukemic blast cells. These leukemias have a grave prognosis because they can develop a leukostasis syndrome which describes: the acute onset of pulmonary failure and, often, neurologic deficits and disseminated intravascular coagulation (DIC). The leukostasis is produced by the mechanical obstruction of vascular bed by blast cells, which can be induced by the spontaneous tumor lysis or as a side effect of cytotoxic drugs. So, hyperleukocytic leukemias require early and vigorous measures to decrease the white blood cell count, using leukapheresis and/or chemotherapy, before pulmonary failure exists. Then, it is possible to reverse the lesions. We report two cases of acute myeloblastic leukemia with a white blood count > 100 x 10(9)/l, that developed a respiratory distress syndrome and died. The postmortem examination has been done in one of the cases.

  10. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 1 2010-10-01 2010-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public... Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included in...

  11. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 1 2011-10-01 2011-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public... Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included in...

  12. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public... Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included in...

  13. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public... Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included in...

  14. 42 CFR 81.24 - Guidelines for leukemia.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Guidelines for leukemia. 81.24 Section 81.24 Public... Causation § 81.24 Guidelines for leukemia. (a) For claims involving leukemia, DOL will calculate one or more probability of causation estimates from up to three of the four alternate leukemia risk models included in...

  15. Veliparib and Temozolomide in Treating Patients With Acute Leukemia

    ClinicalTrials.gov

    2017-01-31

    Accelerated Phase of Disease; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21); (q22; q22.1); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22.3;q23.3); MLLT3-KMT2A; Adult Acute Promyelocytic Leukemia With PML-RARA; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; Adult T Acute Lymphoblastic Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Blastic Phase; Chronic Myelomonocytic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Differences in the Importance of Mast Cells, Basophils, IgE, and IgG versus That of CD4(+) T Cells and ILC2 Cells in Primary and Secondary Immunity to Strongyloides venezuelensis.

    PubMed

    Mukai, Kaori; Karasuyama, Hajime; Kabashima, Kenji; Kubo, Masato; Galli, Stephen J

    2017-05-01

    There is evidence that mast cells, basophils, and IgE can contribute to immune responses to parasites; however, the relative levels of importance of these effector elements in parasite immunity are not fully understood. Previous work in Il3-deficient and c-kit mutant Kit(W/W-v) mice indicated that interleukin-3 and c-Kit contribute to expulsion of the intestinal nematode Strongyloides venezuelensis during primary infection. Our findings in mast cell-deficient Kit(W-sh/W-sh) mice and two types of mast cell-deficient mice that have normal c-kit ("Hello Kitty" and MasTRECK mice) confirmed prior work in Kit(W/W-v) mice that suggested that mast cells play an important role in S. venezuelensis egg clearance in primary infections. We also assessed a possible contribution of basophils in immune responses to S. venezuelensis By immunohistochemistry, we found that numbers of basophils and mast cells were markedly increased in the jejunal mucosa during primary infections with S. venezuelensis Studies in basophil-deficient Mcpt8(DTR) mice revealed a small but significant contribution of basophils to S. venezuelensis egg clearance in primary infections. Studies in mice deficient in various components of immune responses showed that CD4(+) T cells and ILC2 cells, IgG, FcRγ, and, to a lesser extent, IgE and FcεRI contribute to effective immunity in primary S. venezuelensis infections. These findings support the conclusion that the hierarchy of importance of immune effector mechanisms in primary S. venezuelensis infection is as follows: CD4(+) T cells/ILC2 cells, IgG, and FcRγ>mast cells>IgE and FcεRI>basophils. In contrast, in secondary S. venezuelensis infection, our evidence indicates that the presence of CD4(+) T cells is of critical importance but mast cells, antibodies, and basophils have few or no nonredundant roles. Copyright © 2017 American Society for Microbiology.

  17. The effects of thymoquinone and Doxorubicin on leukemia and cardiomyocyte cell lines.

    PubMed

    Brown, R Keith; Wilson, Gerri; Tucci, Michelle A; Benghuzzi, Hamed A

    2014-01-01

    Acute Lymphoblastic Leukemia remains the most common cancer for children, and if left untreated is rapidly fatal. The gold standard for treatment of ALL in children is with a class of drugs known as the antracyclines. Long term outcomes following treatment of leukemia with antracylines can result in cardiac abnormalities including arrhythmias, congestive heart failure, myocardial infarction, hypertension and left ventricular failure. Thymoquinone is a natural product that has demonstrated anti-proliferative, anti-inflammatory, anti-cancer, and chemo-protective effects in control trials as well as a reduction in cardiotoxicity in antracyline treated rats. The aims of the study were to determine if thymoqunione could be used to reduce leukemia cell viability without injuring primary cardiomyocyte, and to determine its effects if used in conjunction with a known chemotherapeutic agent. Cellular viability and morphological changes were observed in the, RAW leukemia cells and cardiac myocytes following treatment with thymoquinone, antracyline (doxorubicin), alone and in combination for 24, 48 and 72 hours. The results suggest that thymoquinone treatment in RAW leukemia cells reduced the cell number without altering the morphology, while doxorubicin reduced cell number and induced spindle cell formation and increased cellular damage. Findings also suggest RAW cell apoptosis increased in combination therapy with thymoquinone and doxorubicin. Thymoquinone administered to cardiomyocytes showed similar morphological changes as control over time in culture; whereas doxorubicin treated cells showed evidence of loss of connectivity and disruption of cell membranes. Combination treatment with doxorubicin and thymoquinone demonstrated significant cardiac myocyte survival at concentrations when used alone were able to reduce the leukemia cells. Overall, the data is promising and may provide a treatment regime to protect the heart tissue. Additional work is warrant to understand

  18. Perspectives on the Causes of Childhood Leukemia

    PubMed Central

    Wiemels, Joseph

    2013-01-01

    Acute leukemia is the most common cancer in children but the causes of the disease in the majority of cases are not known. About 80% are precursor-B cell in origin (CD19+, CD10+), and this immunophenotype has increased in incidence over the past several decades in the Western world. Part of this increase may be due to the introduction of new chemical exposures into the child's environment including parental smoking, pesticides, traffic fumes, paint and household chemicals. However, much of the increase in leukemia rates is likely linked to altered patterns of infection during early childhood development, mirroring causal pathways responsible for a similarly increased incidence of other childhood-diagnosed immune-related illnesses including allergy, asthma, and type 1 diabetes. Factors linked to childhood leukemia that are likely surrogates for immune stimulation include exposure to childcare settings, parity status and birth order, vaccination history, and population mixing. In case-control studies, acute lymphoblastic leukemia (ALL) is consistently inversely associated with greater exposure to infections, via daycare and later birth order. New evidence suggests also that children who contract leukemia may harbor a congenital defect in immune responder status, as indicated by lower levels of the immunosuppressive cytokine IL-10 at birth in children who grow up to contract leukemia, as well as higher need for clinical care for infections within the first year of life despite having lower levels of exposure to infections. One manifestation of this phenomenon may be leukemia clusters which tend to appear as a leukemia “outbreak” among populations with low herd immunity to a new infection. Critical answers to the etiology of childhood leukemia will require incorporating new tools into traditional epidemiologic approaches – including the classification of leukemia at a molecular scale, better exposure assessments at all points in a child's life, a comprehensive

  19. Vorinostat and Idarubicin in Treating Patients With Relapsed or Refractory Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes

  20. 211^At-BC8-B10 Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2017-09-13

    Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; CD45-Positive Neoplastic Cells Present; Chronic Myelomonocytic Leukemia; Myelodysplastic Syndrome With Excess Blasts; Recurrent Adult Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia

  1. Topotecan Hydrochloride and Carboplatin With or Without Veliparib in Treating Advanced Myeloproliferative Disorders and Acute Myeloid Leukemia or Chronic Myelomonocytic Leukemia

    ClinicalTrials.gov

    2017-09-21

    Acute Myeloid Leukemia; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Myelodysplastic/Myeloproliferative Neoplasm; Myelofibrosis; Polycythemia Vera; Recurrent Adult Acute Myeloid Leukemia; Refractory Acute Myeloid Leukemia

  2. Cytogenetic, clinical, and cytologic characteristics of radiotherapy-related leukemias

    SciTech Connect

    Philip, P.; Pedersen-Bjergaard, J.

    1988-04-01

    From 1978 to 1985, we observed eight cases of acute nonlymphocytic leukemia or preleukemia, three cases of acute lymphoblastic leukemia, and three cases of chronic myeloid leukemia in patients previously treated exclusively with radiotherapy for other tumor types. The latent period from administration of radiotherapy to development of leukemia varied between 12 and 243 months. Clonal chromosome aberrations reported previously as characteristic of acute nonlymphocytic leukemia following therapy with alkylating agents were observed in three of the eight patients with acute nonlymphocytic leukemia (5q- and -7) and in two of the three patients with acute lymphoblastic leukemia (-7 and 12p-). All three patients with radiotherapy-related chronic myeloid leukemia presented a t(9;22)(q34;q11). The results suggest that cytogenetic characteristics may reflect the etiology in radiation-induced acute leukemias, whereas radiation-related chronic myeloid leukemia does not seem to differ chromosomally from de novo cases of the disease.

  3. Advances in acute lymphoblastic leukemia.

    PubMed

    Randolph, Tim R

    2004-01-01

    Current literature. Acute lymphoblastic leukemia (ALL) is a stem cell disorder characterized by an overproduction of lymphoblasts in the bone marrow that eventually spill into circulation, producing lymphocytosis. As with the other acute leukemias, the most common symptoms experienced by patients include fatigue, bleeding, and recurrent infections resulting from the suppression of normal hematopoiesis in the bone marrow by the accumulating blasts. ALL primarily affects children and exhibits the best response to standard chemotherapy as compared to acute myeloblastic leukemias (AML). Further, remission rates are highest among ALL patients, many of whom are experiencing sustained remissions suggesting cure. In light of early treatment successes, researchers began to investigate modifications of standard treatment regimens to accommodate variability in weight, age, and response to therapy among children with ALL. Individualized treatment plans were implemented where some patients received a reduced intensity course of therapy to minimize drug toxicity while others received drug intensification to maximize response. More recently, research efforts have been directed at the elucidation of leukemogenic mechanisms implicated in ALL to identify specific protein mutants that can be used to design drugs tailored to interfere with the activity of these mutant protein targets. Identification of chimeric proteins produced from chromosomal translocations and gene expression profiles from microarray analyses are the primary techniques used to identify the potential therapeutic targets. Several reliable prognostic indicators have been identified and are being used to improve therapeutic planning and outcome prediction in ALL patients. Individualized treatment regimens have been developed based on the specific characteristics of each patient to minimize treatment related adverse events and maximize response. Through the use of cytogenetic, molecular, and microarray testing, ALL

  4. Asparaginase in acute lymphoblastic leukemia.

    PubMed

    Kawedia, Jitesh D; Rytting, Michael E

    2014-09-01

    Cure rates in pediatric acute lymphoblastic leukemia have significantly improved over the past decades. Now, almost 90% of children will survive the disease. The cure rates in adolescents, young adults, and adults have not kept pace with the improvements in younger patients, even though almost an equal proportion of adult patients achieve complete remission as their pediatric counterparts. Differences in treatment regimens might be important. Intensive use of asparaginase has been a key component of successful pediatric therapy. In this review, we focus on the use of asparaginase and the potential of optimizing asparaginase use via monitoring to minimize adverse drug events and improve efficacy of the drug.

  5. Release of Elastase from Purified Human Lung Mast Cells and Basophils. Identification as a Hageman Factor Cleaving Enzyme

    DTIC Science & Technology

    1989-01-01

    heterogeneity and hyper- plasia in bleomycin -induced pulmonary fibrosis of rats. Am. Rev. Respir. Dis. 130:.797-902. 40. AGius, R. M., R. C. GoDFREY, and S. T...been shown to be elevated in human pulmonary disorders. Although the HF cleaving assay has been used to demonstrate the presence of functional elastase...FUJLMER, and R. G. CRYSTAL. 1979. Ultrastructure of pulmonary mast cells in patients with fibrotic lung disorders. Lab, Invest. 40-.717-34. 38

  6. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Germ line mutations associated with leukemias.

    PubMed

    Porter, Christopher C

    2016-12-02

    Several genetic syndromes have long been associated with a predisposition to the development of leukemia, including bone marrow failure syndromes, Down syndrome, and Li Fraumeni syndrome. Recent work has better defined the leukemia risk and outcomes in these syndromes. Also, in the last several years, a number of other germ line mutations have been discovered to define new leukemia predisposition syndromes, including ANKRD26, GATA2, PAX5, ETV6, and DDX41 In addition, data suggest that a substantial proportion of patients with therapy related leukemias harbor germ line mutations in DNA damage response genes such as BRCA1/2 and TP53 Recognition of clinical associations, acquisition of a thorough family history, and high index-of-suspicion are critical in the diagnosis of these leukemia predisposition syndromes. Accurate identification of patients with germ line mutations associated with leukemia can have important clinical implications as it relates to management of the leukemia, as well as genetic counseling of family members. © 2016 by The American Society of Hematology. All rights reserved.

  8. [Clinical and hematologic features of pediatric leukemias].

    PubMed

    Hasanbegović, Edo

    2006-01-01

    to present main clinical and hematologic features of pediatric leukemias treated at Hematooncologic department of Pediatric Clinic in Sarajevo during last 7 years. In retrospective study we followed up children with leukemia aged 0-15 who were treated during period of 01.01.1997-31.12.2003. at Hematooncologic department on Pediatric Clinic in Sarajevo. A total number of patient with leukemia was 130 of them 112 (83.2%) had acute lymphoblastic leukemia (ALL), 16 (12.3%) of them had acute myeloid leukemia (AML) and 2 (1.5%) patients had chronic myeloid leukemia (CML). There were 84 (64.6%) boys and 46 (35.4%) girls. Median age of newly diagnosed patients was 6 years and 4 months. Dominant clinical signs were: high temperature-72.9%, fatigue and paleness-74.8% and bone pain-87.9%. Most of the children had leucocitosis (51.5%), anemia (56.1%) and trombocitopenia (57.5%). Most frequent signs at the beginning of the illness are general symptoms like fatigue, unclear febrile state and accented bone pains. Those united signs with complete blood picture finding should be enough reason for suspicion under possible leukemia.

  9. Bosutinib for Chronic Myeloid Leukemia.

    PubMed

    Breccia, Massimo; Binotto, Gianni

    In recent years the availability of several tyrosine kinase inhibitors (TKI) in the therapeutic armamentarium for chronic myeloid leukemia has dramatically changed the objectives and expectations of healthcare providers and patients. For many, but not all, patients the forerunner of TKI, imatinib, is still an excellent treatment option. Unfortunately, nearly 30-40% of imatinib-treated patients discontinue therapy in the long-term, because of failure and/or intolerance. Second-generation tyrosine kinase inhibitors are more potent drugs which are suitable for treatment of approximately 50% of patents for whom imatinib is unsuitable, and with high success and rapid responses. Bosutinib, an orally bioavailable Src/Abl tyrosine kinase inhibitor, has proved to be effective in vitro against resistant chronic myeloid leukemia cells that do not harbor the T315I or V299L ABL kinase domain mutations. During clinical development the manageable safety profile of bosutinib have become evident for both simple and more advanced treatment. In this review we summarize preclinical and clinical data for bosutinib and discuss its ideal field of action in comparison with other TKI.

  10. Therapy-related Myeloid Leukemia

    PubMed Central

    Godley, Lucy A.; Larson, Richard A.

    2008-01-01

    Therapy-related myelodysplastic syndrome and acute myeloid leukemia (t-MDS/t-AML) are thought to be the direct consequence of mutational events induced by chemotherapy, radiation therapy, immunosuppressive therapy, or a combination of these modalities, given for a pre-existing condition. The outcomes for these patients have been poor historically compared to people who develop de novo AML. The spectrum of cytogenetic abnormalities in t-AML is similar to de novo AML, but the frequency of unfavorable cytogenetics, such as a complex karyotype or deletion or loss of chromosomes 5 and/or 7, is considerably higher in t-AML. Survival varies according to cytogenetic risk group in t-AML patients, with better outcomes being observed in those with favorable-risk karyotypes. Treatment recommendations should be based on performance status and karyotype. A deeper understanding of the factors that predispose patients to the development of therapy-related myeloid leukemia would help clinicians monitor patients more carefully after treatment for a primary condition. Ultimately, this knowledge could influence initial treatment strategies with the goal of decreasing the incidence of this serious complication. PMID:18692692

  11. [Apoptosis in chronic lymphocytic leukemia].

    PubMed

    Giordano, M

    2000-01-01

    Chronic lymphocytic leukemia of B cells (B-CLL) is the most prevalent leukemia in the Occidental Hemisphere. It is characterized by a progressive accumulation of monoclonal CD5+ B lymphocytes, with low amounts of surface Ig. Most B-CLL cells are arrested in the G0 phase of the cell cycle; therefore their accumulation in vivo appears to result from the inhibition of apoptosis which has been attributed to over-expression of the anti-apoptotic protein Bcl-2. When cultured in vitro, spontaneous apoptosis occurs, suggesting the existence in vivo of survival-promoting factors. We here show that non-malignant leukocytes, particularly monocytes and NK cells, are able to inhibit B-CLL cells apoptosis, at least in part, through the release of soluble factors. Neutralizing antibodies directed to interferon-gamma or IL-4 only partially abolish the protecting effects of accessory cells suggesting that they are not the main cytokines involved. Increased apoptosis of B-CLL cells is not associated with modifications in the expression of Bcl-2, Fas or Fas ligand. Considering that B-CLL is associated to autoimmune phenomena and recurrent infections due to hypogammaglobulinemia, it should be interesting to correlate the activation of immune responses with disease progression.

  12. Leukemia cutis and facial nerve palsy as presenting symptoms of acute lymphoblastic leukemia.

    PubMed

    Gold, Heidi L; Grynspan, David; Kanigsberg, Nordau

    2014-01-01

    Leukemia cutis and facial nerve palsy are rare presenting symptoms of leukemia. This report describes a case of acute T-cell lymphoblastic leukemia (ALL) presenting with only these two symptoms, a presentation of ALL that, to our knowledge, has not been previously described. It serves to alert physicians to look for underlying malignancy in the setting of cutaneous findings associated with facial nerve palsy. © 2014 Wiley Periodicals, Inc.

  13. Leukemia inhibitory factor induces neurotransmitter switching in transgenic mice.

    PubMed Central

    Bamber, B A; Masters, B A; Hoyle, G W; Brinster, R L; Palmiter, R D

    1994-01-01

    Leukemia inhibitory factor (LIF) is a cytokine growth factor that induces rat sympathetic neurons to switch their neurotransmitter phenotype from noradrenergic to cholinergic in vitro. To test whether LIF can influence neuronal differentiation in vivo, we generated transgenic mice that expressed LIF in pancreatic islets under the control of the insulin promoter and evaluated the neurotransmitter phenotype of the pancreatic sympathetic innervation. We also used the insulin promoter to coexpress nerve growth factor in the islets, which greatly increased the density of sympathetic innervation and facilitated analysis of the effects of LIF. Our data demonstrate that tyrosine hydroxylase and catecholamines declined and choline acetyltransferase increased in response to LIF. We conclude that LIF can induce neurotransmitter switching of sympathetic neurons in vivo. Images PMID:7914698

  14. Hairy Cell Leukemia and Bone Pain.

    PubMed

    Streu, Erin

    2016-01-01

    Hairy cell leukemia is a relatively rare but distinct B-cell lympho-proliferative disorder of the blood, bone marrow, and spleen that accounts for only 2% of all adult leukemia cases. The median age at presentation is 50-55 years, with a 4:1 male to female predominance. Although considered uncommon, a number of unusual clinical presentations have been noted in the literature, including the presence of peripheral lymphadenopathy, lytic bone lesions, skin involvement, organ involvement, and central nervous system involvement. Unlike the clinical management of other hematologic malignancies, no current system is used to stage hairy cell leukemia.

  15. Leukemia studies continue to draw a blank

    SciTech Connect

    Williams, N.

    1996-04-19

    When large numbers of childhood thyroid cancer cases began showing up in the three most heavily contaminated republics about Chernobyl 5 years after the accident, many thought there would be a jump in the incidence of leukemia. Studies of Japanese atomic bomb survivors and other radiation accidents have pinpointed leukemia as the key early indicator of the effects of radiation. But so far, thyroid cancer remains an anomaly. Three major international studies have so far failed to detect any measurable increase in leukemia - or any other cancers - in the general population. This paper describes the studies and discusses possible reasons as well as what might happen in the future.

  16. Pilot study of Bortezomib for Patients with Imatinib-Refractory Chronic Myeloid Leukemia in Chronic or Accelerated Phase

    PubMed Central

    Santos, Fabio P S; Kantarjian, Hagop; McConkey, David; O'Brien, Susan; Faderl, Stefan; Borthakur, Gautam; Ferrajoli, Alessandra; Wright, John; Cortes, Jorge

    2015-01-01

    Background Proteasome inhibitors are anticancer compounds that disrupt the proteolytic activity of the proteasome and lead to tumor cell growth arrest and apoptosis. Bortezomib is a proteasome inhibitor that is currently approved for use in multiple myeloma and mantle cell lymphoma. It induces apoptosis of chronic myeloid leukemia (CML) cells in vitro, but the activity of bortezomib in patients with imatinib-resistant CML is unknown. Methods We conducted a pilot trial to evaluate the activity of single agent bortezomib in CML. Seven patients with imatinib-refractory CML were treated with bortezomib at a dose of 1.5 mg/m2 on days 1, 4, 8 and 11 every 3 weeks. Results The median number of cycles received was 2. No patient had a hematologic or cytogenetic response. Three patients had a temporary decrease in basophil counts associated with therapy with bortezomib. Six patients developed grade 3-4 nonhematological toxicities. Conclusion Bortezomib had minimal efficacy and considerable toxicity in patients with imatinib-refractory CML. Further studies should focus on alternative approaches to employ proteasome inhibitors in the treatment of CML, such as in combination with tyrosine kinase inhibitors or as a strategy to eradicate leukemic stem cells. PMID:21816374

  17. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2017-03-27

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  18. Speed of leukemia development and genetic diversity in xenograft models of T cell acute lymphoblastic leukemia

    PubMed Central

    Poglio, Sandrine; Lewandowski, Daniel; Calvo, Julien; Caye, Aurélie; Gros, Audrey; Laharanne, Elodie; Leblanc, Thierry; Landman-Parker, Judith; Baruchel, André; Soulier, Jean; Ballerini, Paola; Clappier, Emmanuelle; Pflumio, Françoise

    2016-01-01

    T cell acute lymphoblastic leukemia (T-ALL) develops through accumulation of multiple genomic alterations within T-cell progenitors resulting in clonal heterogeneity among leukemic cells. Human T-ALL xeno-transplantation in immunodeficient mice is a gold standard approach to study leukemia biology and we recently uncovered that the leukemia development is more or less rapid depending on T-ALL sample. The resulting human leukemia may arise through genetic selection and we previously showed that human T-ALL development in immune-deficient mice is significantly enhanced upon CD7+/CD34+ leukemic cell transplantations. Here we investigated the genetic characteristics of CD7+/CD34+ and CD7+/CD34− cells from newly diagnosed human T-ALL and correlated it to the speed of leukemia development. We observed that CD7+/CD34+ or CD7+/CD34− T-ALL cells that promote leukemia within a short-time period are genetically similar, as well as xenograft-derived leukemia resulting from both cell fractions. In the case of delayed T-ALL growth CD7+/CD34+ or CD7+/CD34− cells were either genetically diverse, the resulting xenograft leukemia arising from different but branched subclones present in the original sample, or similar, indicating decreased fitness to mouse micro-environment. Altogether, our work provides new information relating the speed of leukemia development in xenografts to the genetic diversity of T-ALL cell compartments. PMID:27191650

  19. Cordycepin disrupts leukemia association with mesenchymal stromal cells and eliminates leukemia stem cell activity

    PubMed Central

    Liang, Shu-Man; Lu, Yi-Jhu; Ko, Bor-Sheng; Jan, Yee-Jee; Shyue, Song-Kun; Yet, Shaw-Fang; Liou, Jun-Yang

    2017-01-01

    Maintaining stemness of leukemic stem cells (LSCs) and reciprocal interactions between leukemia and stromal cells support leukemic progression and resistance to chemotherapy. Targeting the niche-based microenvironment is thus a new approach for leukemia therapy. Cordycepin is an analogue of adenosine and has been suggested to possess anti-leukemia properties. However, whether cordycepin influences association of leukemia and mesenchymal stromal cells has never been investigated. Here we show that cordycepin reduces CD34+CD38− cells in U937 and K562 cells and induces Dkk1 expression via autocrine and paracrine regulation in leukemia and mesenchymal stromal/stem cells (MSCs). Cordycepin suppresses cell attachment of leukemia with MSCs and downregulates N-cadherin in leukemia and VCAM-1 in MSCs. Moreover, incubation with leukemic conditioned media (CM) significantly induces IL-8 and IL-6 expression in MSCs, which is abrogated by cordycepin. Suppression of leukemic CM-induced VCAM-1 and IL-8 by cordycepin in MSCs is mediated by impairing NFκB signaling. Finally, cordycepin combined with an adenosine deaminase inhibitor prolongs survival in a leukemic mouse model. Our results indicate that cordycepin is a potential anti-leukemia therapeutic adjuvant via eliminating LSCs and disrupting leukemia-stromal association. PMID:28266575

  20. T-cell prolymphocytic leukemia in a 63-year-old female with a pre-existing T-cell large granular lymphocytic leukemia: metachronous T-cell leukemias with discordant subset restrictions (CD4 versus CD8) and distinct clonal identities.

    PubMed

    Wei, Qiang; Papavassiliou, Paulie; Rehder, Catherine; Sebastian, Siby; Wang, Endi

    2014-12-01

    A 55-year-old female with T-cell large granular lymphocytic leukemia (T-LGL) (CD8+) was initially treated with anti-thymocyte globulin and then cyclosporine due to anemia/neutropenia. While the severity of cytopenia varied with the therapy, the T-LGL persisted. Eight years after the initial diagnosis, she developed lymphadenopathy and hepatosplenomegaly. A complete blood cell count revealed leukocytosis, anemia and thrombocytopenia with ∼ 80% lymphocytes. In contrast to the LGL cells, the blood lymphocytes at this time were medium-large in size and had oval/irregular nuclei, condensed chromatin, indistinct nucleoli and a moderate amount of basophilic cytoplasm, many with elongated vacuoles, and some with cytoplasmic projections. The abnormal lymphocytes comprised ∼ 30% of the bone marrow cellularity with interstitial infiltrates/aggregates. Immunophenotypic analyses demonstrated a T-cell neoplasm with features suggestive of T-cell prolymphocytic leukemia (T-PLL) (CD4+). Cytogenetic analysis revealed a novel clone with complex abnormalities. PCR-based TRG gene rearrangement studies detected a clonal amplicon distinct from that of the preexisting T-LGL. Because of the chronological sequence of the two T-cell neoplasms, this case was initially considered an aggressive transformation of T-LGL. However, this was ultimately excluded by a discordant CD4-subset restriction and the presence of a distinct clonal identity. While these two T-cell neoplasms may have intrinsic connections, the underlying pathogenesis remains to be investigated. Copyright © 2014 Elsevier GmbH. All rights reserved.

  1. 5-Fluoro-2'-Deoxycytidine and Tetrahydrouridine in Treating Patients With Acute Myeloid Leukemia or Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-06-03

    Adult Acute Myeloid Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  2. Choline Magnesium Trisalicylate and Combination Chemotherapy in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-02-01

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-04-18

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2017-09-08

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  5. S1312, Inotuzumab Ozogamicin and Combination Chemotherapy in Treating Patients With Relapsed or Refractory Acute Leukemia

    ClinicalTrials.gov

    2017-02-23

    Acute Leukemias of Ambiguous Lineage; B-cell Adult Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Burkitt Lymphoma

  6. Alvocidib, Cytarabine, and Mitoxantrone in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-06-03

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  7. Tipifarnib and Etoposide in Treating Older Patients With Newly Diagnosed, Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-01

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  8. Omacetaxine Mepesuccinate, Cytarabine, and Decitabine in Treating Older Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-05

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  9. S0432 Tipifarnib in Treating Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-14

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  10. Lenalidomide in Treating Older Patients With Acute Myeloid Leukemia Who Have Undergone Stem Cell Transplant

    ClinicalTrials.gov

    2015-03-02

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; Recurrent Adult Acute Myeloid Leukemia

  11. Selumetinib in Treating Patients With Recurrent or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-07-06

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Myelodysplastic Syndromes; Myelodysplastic/Myeloproliferative Neoplasms; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  12. Chronic myeloid leukemia in blast crisis treated with imatinib 600 mg: outcome of the patients alive after a 6-year follow-up.

    PubMed

    Palandri, Francesca; Castagnetti, Fausto; Testoni, Nicoletta; Luatti, Simona; Marzocchi, Giulia; Bassi, Simona; Breccia, Massimo; Alimena, Giuliana; Pungolino, Ester; Rege-Cambrin, Giovanna; Varaldo, Riccardo; Miglino, Maurizio; Specchia, Giorgina; Zuffa, Eliana; Ferrara, Felicetto; Bocchia, Monica; Saglio, Giuseppe; Pane, Fabrizio; Alberti, Daniele; Martinelli, Giovanni; Baccarani, Michele; Rosti, Gianantonio

    2008-12-01

    Imatinib mesylate is the first line treatment for chronic myeloid leukemia. In patients with advanced phase of the disease, the advent of imatinib significantly increased survival. However, few long-term data, based on large, prospective and controlled trials are available on the outcome of these patients. We conducted a phase II trial of imatinib 600 mg daily in patients with chronic myeloid leukemia in blast crisis. The return to chronic phase was defined as <15% blasts and <30% blasts plus promyelocytes in blood or bone marrow and <20% peripheral basophils. A complete hematologic response required the normalization of platelet and white cell differential counts and absence of extramedullary involvement. Cytogenetic response was assessed by the standard banding technique and rated as usual. Ninety-two patients were enrolled (20 with lymphoid blast crisis and 72 with myeloid blast crisis). Forty-six patients (50%) returned to chronic phase, and 24 patients (26%) achieved also a complete hematologic response. Sixteen patients (17%) had a cytogenetic response (9 complete, 1 partial, and 6 minor or minimal). The complete cytogenetic response was subsequently lost by all but two patients between 2 and 12 months after first having achieved it: the median duration of complete cytogenetic response was 7 months. All responses were sustained for a minimum of 4 weeks. The median survival of all the patients was 7 months. After a median observation time of 66 months, seven (8%) patients are alive. Three of these patients are on imatinib treatment (1 in complete hematologic remission, 1 in partial cytogenetic response and 1 in complete cytogenetic remission). Three patients are in complete remission after allogeneic stem cell transplantation. One patient is alive in blast crisis, on therapy with a second-generation tyrosine kinase inhibitor. Imatinib was effective and safe in the short-term treatment of chronic myeloid leukemia in blast crisis, but longer-term outcome was not

  13. Tositumomab and Iodine I 131 Tositumomab in Treating Patients With Chronic Lymphocytic Leukemia or Small Lymphocytic Lymphoma in First Remission

    ClinicalTrials.gov

    2015-08-04

    Lymphoid Leukemia in Remission; Stage I Chronic Lymphocytic Leukemia; Stage II Chronic Lymphocytic Leukemia; Stage III Chronic Lymphocytic Leukemia; Stage III Small Lymphocytic Lymphoma; Stage IV Chronic Lymphocytic Leukemia; Stage IV Small Lymphocytic Lymphoma

  14. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2017-09-05

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  15. Bioelectrical Impedance Measurement for Predicting Treatment Outcome in Patients With Newly Diagnosed Acute Leukemia

    ClinicalTrials.gov

    2017-08-14

    Acute Undifferentiated Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  16. Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2017-02-17

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  17. Three hematologic malignancies in the same patient: chronic lymphocytic leukemia, followed by chronic myeloid leukemia and acute myeloid leukemia.

    PubMed

    Fattizzo, Bruno; Radice, Tommaso; Cattaneo, Daniele; Pomati, Mauro; Barcellini, Wilma; Iurlo, Alessandra

    2014-01-01

    The co-existence of both chronic myeloid leukemia (CML) and chronic lymphocytic leukemia (CLL) have been described in a few cases, either simultaneously or subsequently presenting. We report an unusual case of three he-matological malignancies in the same patient: CLL, CML, and acute myeloid leukemia (AML). None of the three malignancies shared the same origin, since the marrow sample was negative for BCR-ABL1 transcript at the time of CLL diagnosis, CLL was in remission at CML diagnosis, and CML was in complete cytogenetic response at AML onset, indicating that this was not a blast crisis. Background: Chronic lymphocytic leukemia (CLL) and chronic myeloid leukemia (CML) are the most common proliferative disorders in Western countries, with an incidence of 4.2/100,000/year and 1-1.5/100,000/year, respectively. The co-existence of both CML and CLL is an extremely rare event, even if it has been described in a few cases, either simultaneously or subsequently presenting. Above all, the presence of more than two different hematologic neoplasms has not been described in literature so far. In the present study we report a particular case of a CLL patient, who first developed CML and then acute myeloid leukemia (AML).

  18. Significance of Inactivated Genes in Leukemia: Pathogenesis and Prognosis

    PubMed Central

    Heidari, Nazanin; Abroun, Saeid; Bertacchini, Jessika; Vosoughi, Tina; Rahim, Fakher; Saki, Najmaldin

    2017-01-01

    Epigenetic and genetic alterations are two mechanisms participating in leukemia, which can inactivate genes involved in leukemia pathogenesis or progression. The purpose of this review was to introduce various inactivated genes and evaluate their possible role in leukemia pathogenesis and prognosis. By searching the mesh words “Gene, Silencing AND Leukemia” in PubMed website, relevant English articles dealt with human subjects as of 2000 were included in this study. Gene inactivation in leukemia is largely mediated by promoter’s hypermethylation of gene involving in cellular functions such as cell cycle, apoptosis, and gene transcription. Inactivated genes, such as ASPP1, TP53, IKZF1 and P15, may correlate with poor prognosis in acute lymphoid leukemia (ALL), chronic lymphoid leukemia (CLL), chronic myelogenous leukemia (CML) and acute myeloid leukemia (AML), respectively. Gene inactivation may play a considerable role in leukemia pathogenesis and prognosis, which can be considered as complementary diagnostic tests to differentiate different leukemia types, determine leukemia prognosis, and also detect response to therapy. In general, this review showed some genes inactivated only in leukemia (with differences between B-ALL, T-ALL, CLL, AML and CML). These differences could be of interest as an additional tool to better categorize leukemia types. Furthermore; based on inactivated genes, a diverse classification of Leukemias could represent a powerful method to address a targeted therapy of the patients, in order to minimize side effects of conventional therapies and to enhance new drug strategies. PMID:28580304

  19. Clofarabine, Cytarabine, and G-CSF in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-05-05

    Acute Myeloid Leukemia; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia

  20. Romidepsin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-12-03

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia