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Sample records for eosinophilic leukemia eol-1

  1. Comparative Analysis of Dibutyric cAMP and Butyric Acid on the Differentiation of Human Eosinophilic Leukemia EoL-1 Cells

    PubMed Central

    2015-01-01

    Purification of enough numbers of circulating eosinophils is difficult because eosinophils account for less than 5% peripheral blood leukocytes. Human eosinophilic leukemia EoL-1 cells have been considered an in vitro source of eosinophils as they can differentiate into mature eosinophil-like cells when incubated with dibutyryl cAMP (dbcAMP) or butyric acid. In this study, the viability and phenotypic maturation of EoL-1 cells stimulated by either dbcAMP or butyric acid were comparatively analyzed. After treatment with 100 然 dbcAMP or 0.5 然 butyric acid, EoL-1 cells showed morphological signs of differentiation, although the number of nonviable EoL-1 cells was significantly increased following butyric acid treatment. Stimulation of EoL-1 cells with 0.5 然 butyric acid more effectively induced the expression of mature eosinophil markers than stimulation with dbcAMP. These results suggest that treatment of EoL-1 cells with 0.5 然 butyric acid for limited duration could be an effective strategy for inducing their differentiation. Considering that expression of CCR3 was not sufficient in EoL-1 cells stimulated with 0.5 然 butyric acid, treatment of the chemically stimulated EoL-1 cells with cytokines, which primarily support eosinophil maturation, would help to obtain differentiated EoL-1 cells with greater functional maturity. PMID:26770185

  2. Mechanisms for the proliferation of eosinophilic leukemia cells by FIP1L1-PDGFR{alpha}

    SciTech Connect

    Ishihara, Kenji; Kitamura, Hajime; Hiraizumi, Kenji; Kaneko, Motoko; Takahashi, Aki; Zee, OkPyo; Seyama, Toshio; Hong, JangJa; Ohuchi, Kazuo; Hirasawa, Noriyasu

    2008-02-22

    The constitutively activated tyrosine kinase Fip1-like 1 (FIP1L1)-platelet-derived growth factor receptor {alpha} (PDGFR{alpha}) causes eosinophilic leukemia EoL-1 cells to proliferate. Recently, we demonstrated that histone deacetylase inhibitors suppressed this proliferation and induced the differentiation of EoL-1 cells into eosinophils in parallel with a decrease in the level of FIP1L1-PDGFR{alpha}. In this study, we analyzed the mechanism by which FIP1L1-PDGFR{alpha} induces the proliferation and whether the suppression of cell proliferation triggers the differentiation into eosinophils. The FIP1L1-PDGFR{alpha} inhibitor imatinib inhibited the proliferation of EoL-1 cells and decreased the level of the oncoprotein c-Myc as well as the phosphorylation of extracellular signal-regulated kinase and c-Jun N-terminal kinase (JNK). The proliferation of EoL-1 cells and expression of c-Myc were also inhibited by the MEK inhibitor U0126 and JNK inhibitor SP600125. The expression of the eosinophilic differentiation marker CCR3 was not induced by imatinib. These findings suggest that FIP1L1-PDGFR{alpha} induces the proliferation of EoL-1 cells through the induction of c-Myc expression via ERK and JNK signaling pathways, but is not involved in the inhibition of differentiation toward mature eosinophils.

  3. Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia

    MedlinePLUS

    ... Cancer.Net: Leukemia--Eosinophilic: Treatment Genetic Testing Registry: Myeloproliferative disorder, chronic, with eosinophilia MedlinePlus Encyclopedia: Eosinophil Count--Absolute Seattle Cancer Care Alliance: Hypereosinophilia You might also find information ...

  4. Myeloprolipherative disorder type chronic myeloid leukemia--eosinophilic form.

    PubMed

    Arnautovic-Custovic, Aida; Hasic, Samira; Kopic, Emina; Jahic, Azra; Jovic, Svetlana

    2011-01-01

    Chronic eosinophilic leukemia (CEL) is a very rare form of leucemia in the western world. Adequate response is seldomly achieved after treatment with corticosteroids, interferon-alfa (INF-alfa) and medications containing hydroxi-urea (Litalir). The study presents a patient with CEL with no initial therapeutic response to the use of corticosteroids, INF-alfa and hydroxy-urea, and with neither clinical nor hematological response. After setting a diagnosis of CEL, patient was ordinated Imatinib (Glivec tabbletes) in a daily dose of 200 mg. Two days afterwards there was an evident withdrawal of subjective and clinical symptoms of disease, and the complete blood count showed significant amendment. PMID:21776882

  5. Genetics Home Reference: PDGFRB-associated chronic eosinophilic leukemia

    MedlinePLUS

    ... other types of white blood cells, such as neutrophils or mast cells, in addition to eosinophils. People ... eosinophils (and occasionally other blood cells, such as neutrophils and mast cells) is poorly controlled, leading to ...

  6. EOL-1, the homolog of the mammalian Dom3Z, regulates olfactory learning in C. elegans.

    PubMed

    Shen, Yu; Zhang, Jiangwen; Calarco, John A; Zhang, Yun

    2014-10-01

    Learning is an essential function of the nervous system. However, our understanding of molecular underpinnings of learning remains incomplete. Here, we characterize a conserved protein EOL-1 that regulates olfactory learning in Caenorhabditis elegans. A recessive allele of eol-1 (enhanced olfactory learning) learns better to adjust its olfactory preference for bacteria foods and eol-1 acts in the URX sensory neurons to regulate learning. The mammalian homolog of EOL-1, Dom3Z, which regulates quality control of pre-mRNAs, can substitute the function of EOL-1 in learning regulation, demonstrating functional conservation between these homologs. Mutating the residues of Dom3Z that are critical for its enzymatic activity, and the equivalent residues in EOL-1, abolishes the function of these proteins in learning. Together, our results provide insights into the function of EOL-1/Dom3Z and suggest that its activity in pre-mRNA quality control is involved in neural plasticity. PMID:25274815

  7. Genetics Home Reference: PDGFRA-associated chronic eosinophilic leukemia

    MedlinePLUS

    ... endomyocardial disease, skin rashes, coughing, difficulty breathing, swelling (edema) in the lower limbs, confusion, changes in behavior, ... cancer ; cell ; cell membrane ; chromosome ; chronic ; deletion ; DNA ; edema ; enlarged spleen ; eosinophils ; fusion gene ; gene ; immune response ; ...

  8. Genetics Home Reference: PDGFRA-associated chronic eosinophilic leukemia

    MedlinePLUS

    ... forming the genetic blueprints for making proteins (messenger RNA or mRNA). The PDGFRA gene provides instructions for ... inflammation ; inherited ; leukemia ; ligand ; lymphoma ; mast cells ; messenger RNA ; mRNA ; mutation ; myeloid ; nervous system ; neutrophils ; population ; prevalence ; ...

  9. The Spectrum of FIP1L1-PDGFRA-Associated Chronic Eosinophilic Leukemia

    PubMed Central

    Legrand, Fanny; Renneville, Aline; MacIntyre, Elizabeth; Mastrilli, Samuel; Ackermann, Felix; Cayuela, Jean Michel; Rousselot, Philippe; Schmidt-Tanguy, Aline; Fain, Olivier; Michel, Marc; de Jaureguiberry, Jean-Pierre; Hatron, Pierre-Yves; Cony-Makhoul, Pascale; Lefranc, Didier; S鋝e, Damien; Cottin, Vincent; Hamidou, Mohamed; Lidove, Olivier; Baruchel, Andr; Dubucquoi, Sylvain; Bletry, Olivier; Preudhomme, Claude; Capron, Monique; Prin, Lionel; Kahn, Jean Emmanuel

    2013-01-01

    Abstract Imatinib is the treatment of choice for FIP1L1/PDGFRA (F/P)-associated chronic eosinophilic leukemia (F/P+ CEL), but its optimal dosing, duration, and possibility of discontinuation are still a matter of debate. A retrospective multicenter study was conducted with 44 F/P+ CEL patients identified in the French Eosinophil Network and treated with imatinib. The most frequently involved systems were skin (57%), spleen (52%), and lung (45%), and eosinophilic heart disease was observed in 15 patients (34%). Complete hematologic response (CHR) was obtained in all patients, and complete molecular response (CMR) in 95% of patients (average initial imatinib dose, 165 mg/d). For 29 patients the imatinib dose was tapered with a maintenance dose of 58 mg/d (34 mg/d), allowing sustained CHR and CMR. None of the patients developed resistance during a median follow-up of 52.3 months (range, 1.497.4 mo). Imatinib was stopped in 11 patients; 6 of the patients subsequently relapsed, but 5 remained in persistent CHR or CMR (range, 988 mo). These results confirm that an initial low-dose regimen of imatinib (100 mg/d) followed by a lower maintenance dose can be efficient for obtaining long-term CHR and CMR. Our data also suggest that imatinib can be stopped in some patients without molecular relapse. PMID:23982058

  10. Identification of Ponatinib as a potent inhibitor of growth, migration and activation of neoplastic eosinophils carrying FIP1L1-PDGFRA

    PubMed Central

    Sadovnik, Irina; Lierman, Els; Peter, Barbara; Herrmann, Harald; Suppan, Verena; Stefanzl, Gabriele; Haas, Oskar; Lion, Thomas; Pickl, Winfried; Cools, Jan; Vandenberghe, Peter; Valent, Peter

    2015-01-01

    In chronic eosinophilic leukemia (CEL), the transforming oncoprotein FIP1L1-PDGFRA is a major target of therapy. In most patients, the tyrosine kinase inhibitor (TKI) imatinib induces complete remission. For patients who are intolerant or resistant, novel TKI have been proposed. We examined the in vitro effects of 14 kinase blockers on growth and function of EOL-1 cells, a FIP1L1-PDGFRA+ eosinophil cell line. Major growth-inhibitory effects were seen with all PDGFR-blocking agents, with IC50 values in the low nM-range: ponatinib: 0.1-0.2 nM, sorafenib: 0.1-0.2 nM, masitinib: 0.2-0.5 nM, nilotinib: 0.2-1 nM, dasatinib: 0.5-2 nM, sunitinib: 1-2 nM, midostaurin: 5-10 nM. These drugs were also found to block activation of PDGFR-downstream signaling molecules, including Akt, S6, and STAT5 in EOL-1 cells. All effective TKI produced apoptosis in EOL-1 cells as determined by microscopy, Annexin-V/PI, and caspase-3-staining. In addition, PDGFR-targeting TKI were found to inhibit cytokine-induced migration of EOL-1 cells. In all bioassays employed, ponatinib was found to be the most potent compound in EOL-1 cells. In addition, ponatinib was found to downregulate expression of the activation-linked surface antigen CD63 on EOL-1 cells, and to suppress growth of primary neoplastic eosinophils. We also examined drug effects on Ba/F3 cells expressing two clinically relevant imatinib-resistant mutant-forms of FIP1L1-PDGFRA, namely T674I and D842V. Strong inhibitory effects on both mutants were only seen with ponatinib. In summary, novel PDGFR-targeting TKI may be alternative agents for the treatment of patients with imatinib-resistant CEL. Although several different PDGFR-targeting agents are effective, the most potent drug appears to be ponatinib. PMID:24407160

  11. Leukemia -- Eosinophilic

    MedlinePLUS

    ... medical, surgical, radiation, gynecologic, and pediatric oncologists, oncology nurses, physician assistants, social workers, and patient advocates. Cancer.Net ... with Side Effects Follow-Up Care Survivorship Questions ...

  12. Characterization of a receptor for interleukin-5 on human eosinophils and the myeloid leukemia line HL-60

    SciTech Connect

    Ingley, E.; Young, I.G. )

    1991-07-15

    Interleukin-5 (IL-5) promotes the growth and differentiation of human eosinophils and may regulate the selective eosinophilia and eosinophil activation seen in certain diseases. Radiolabeled recombinant human IL-5 (hIL-5) was used to characterize the IL-5 receptor present on normal human eosinophils and on the myeloid leukemia line HL-60, which can be induced to differentiate into eosinophilic cells. Binding studies with eosinophils and HL-60 cells grown under alkaline conditions demonstrated similar high-affinity binding sites for hIL-5 on both cell types with kd values of approximately 400 pmol/L. The binding observed was specific in that it was not inhibited by hIL-3, human granulocyte-macrophage colony-stimulating factor, or hIL-2. Binding studies with a number of other human cell lines, including a B-lymphoma line, and with lymphocyte and neutrophil preparations were also performed, but IL-5 receptors were not detectable on these cells. The number of hIL-5 receptors on HL-60 cells could be correlated with its propensity to differentiate towards an eosinophilic cell type. Expression of hIL-5 receptors on HL-60 cells was upregulated by butyric acid under alkaline conditions, downregulated by hIL-3, virtually eliminated by dimethyl sulfoxide and hIL-5, while hIL-2 had no detectable effect. One major 125I-hIL-5-crosslinked complex of 75 to 85 Kd in Mr was detected on HL-60 cells using crosslinking agents giving a molecular mass of 55 to 60 Kd for the hIL-5 receptor itself. Studies using cellular autoradiography showed that IL-5 receptors were evenly distributed on eosinophils but that receptor distribution on HL-60 cells was noticeably heterogeneous. Eosinophils were the only cells in slides prepared from peripheral blood that had detectable levels of IL-5 receptors in agreement with the specific action of IL-5 on the human eosinophil lineage.

  13. Eosinophil count - absolute

    MedlinePLUS

    ... Certain fungus infections Asthma Autoimmune diseases Eczema Hay fever Leukemia and other blood disorders A lower-than-normal eosinophil count may be due to: Alcohol intoxication Overproduction of certain steroids in the body (such as cortisol)

  14. Novel Association between Vasoactive Intestinal Peptide and CRTH2 Receptor in Recruiting Eosinophils

    PubMed Central

    El-Shazly, Amr E.; Begon, Dominique Y.; Kustermans, Gaelle; Arafa, Mohammad; Dortu, Estelle; Henket, Monique; Lefebvre, Philippe P.; Louis, Renaud; Delvenne, Philippe

    2013-01-01

    We explored the relation between vasoactive intestinal peptide (VIP), CRTH2, and eosinophil recruitment. It is shown that CRTH2 expression by eosinophils from allergic rhinitis (AR) patients and eosinophil cell line (Eol-1 cells) was up-regulated by VIP treatment. This was functional and resulted in exaggerated migratory response of cells against PGD2. Nasal challenge of AR patients resulted in a significant increase of VIP contents in nasal secretion (ELISA), and the immunohistochemical studies of allergic nasal tissues showed significant expression of VIP in association with intense eosinophil recruitment. Biochemical assays showed that VIP-induced eosinophil chemotaxis from AR patients and Eol-1 cells was mediated through the CRTH2 receptor. Cell migration against VIP was sensitive to protein kinase C (PKC) and protein kinase A (PKA) inhibition but not to tyrosine kinase or p38 MAPK inhibition or calcium chelation. Western blot demonstrated a novel CRTH2-mediated cytosol-to-membrane translocation of PKC-?, PKC-?, and PKA-?, -?, and -II?reg in Eol-1 cells upon stimulation with VIP. Confocal images and FACS demonstrated a strong association and co-localization between VIP peptide and CRTH2 molecules. Further, VIP induced PGD2 secretion from eosinophils. Our results demonstrate the first evidence of association between VIP and CRTH2 in recruiting eosinophils. PMID:23168411

  15. Leukemia

    MedlinePLUS

    ... meaning they get worse quickly. chronic lymphocytic leukemia chronic myeloid leukemia acute myeloid leukemia acute lymphocytic leukemia Chronic and Acute Leukemia Chronic lymphocytic leukemia, chronic myeloid leukemia, and acute myeloid leukemia are diagnosed more often ...

  16. Chronic Eosinophilic Leukemia

    MedlinePLUS

    ... Other Funding Find NCI funding for small business innovation, technology transfer, and contracts Training Cancer Training at ... or symptoms . It may be found during a routine blood test . Signs and symptoms may occur as ...

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

    ClinicalTrials.gov

    2016-03-11

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; 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

  18. FIP1L1/PDGFRalpha synergizes with SCF to induce systemic mastocytosis in a murine model of chronic eosinophilic leukemia/hypereosinophilic syndrome.

    PubMed

    Yamada, Yoshiyuki; Sanchez-Aguilera, Abel; Brandt, Eric B; McBride, Melissa; Al-Moamen, Nabeel J H; Finkelman, Fred D; Williams, David A; Cancelas, Jose A; Rothenberg, Marc E

    2008-09-15

    Expression of the fusion gene FIP1-like 1/platelet-derived growth factor receptor alpha (FIP1L1/PDGFRalpha, F/P) and dysregulated c-kit tyrosine kinase activity are associated with systemic mastocytosis (SM) and chronic eosinophilic leukemia (CEL)/hypereosinophilic syndrome (HES). We analyzed SM development and pathogenesis in a murine CEL model induced by F/P in hematopoietic stem cells and progenitors (HSCs/Ps) and T-cell overexpression of IL-5 (F/P-positive CEL mice). These mice had more mast cell (MC) infiltration in the bone marrow (BM), spleen, skin, and small intestine than control mice that received a transplant of IL-5 transgenic HSCs/Ps. Moreover, intestinal MC infiltration induced by F/P expression was severely diminished, but not abolished, in mice injected with neutralizing anti-c-kit antibody, suggesting that endogenous stem cell factor (SCF)/c-kit interaction synergizes with F/P expression to induce SM. F/P-expressing BM HSCs/Ps showed proliferation and MC differentiation in vitro in the absence of cytokines. SCF stimulated greater migration of F/P-expressing MCs than mock vector-transduced MCs. F/P-expressing bone marrow-derived mast cells (BMMCs) survived longer than mock vector control BMMCs in cytokine-deprived conditions. The increased proliferation and survival correlated with increased SCF-induced Akt activation. In summary, F/P synergistically promotes MC development, activation, and survival in vivo and in vitro in response to SCF. PMID:18539901

  19. Eosinophilic Fasciitis

    MedlinePLUS

    ... Bone, Joint, and Muscle Disorders Autoimmune Disorders of Connective Tissue Eosinophilic Fasciitis Symptoms Diagnosis Prognosis and Treatment Drugs ... DOCTORS: Go to Professional Version Autoimmune Disorders of Connective Tissue Overview of Autoimmune Disorders of Connective Tissue Systemic ...

  20. [Eosinophilic esophagitis].

    PubMed

    Kusunose, Hiroaki; Ohara, Shuichi

    2015-07-01

    Eosinophilic esophagitis (EoE) is a clinicopathologic condition of increasing recognition and prevalence. Because of elevated total IgE levels and high rates of concurrent allergic diseases compared with the general population, EoE appears to be an antigen-driven immunologic process that caused by allergens like food or aeroallergens. EoE is a disease that features dense intraepithelial infiltration by eosinophils which cause excessive mucosal immunologic reactions which cause several symptoms that mostly involve dysphagia. For establishment of the diagnosis, infiltration of eosinophils (? 20 eosinophils/HPF) should be identified in an esophageal mucosal biopsy specimen. In treatment of patients have a possibility of EoE, proton-pump inhibitors(PPIs) must be tried as first choice. Other proved therapeutic options include topical or systemic corticosteroids, chronic dietary elimination, and esophageal dilation, but local administration of glucocorticoids has recently been reported as useful therapy for EoE. PMID:26165084

  1. Leukemia

    MedlinePLUS

    ... FR. The acute leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, Pa: ... Brien S. The chronic leukemias. In: Goldman L, Schafer AI, eds. Goldman's Cecil Medicine . 24th ed. Philadelphia, Pa: ...

  2. 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. ...

  3. Acute myeloid leukemia (AML-M2) with translocation (8;21) (q22;q22) and abnormal eosinophilic precursors in the bone marrow--a case report.

    PubMed

    Gupta, Oneal; Aggarwal, Roopak; Prasad, Rajni

    2012-02-01

    The translocation (8;21)(q22;q22) is frequently associated with M2 subtype of AML. The authors herein present a case of AML-M2 in a nine-year-old boy without hepatosplenomegaly, lymphadenopathy or any bleeding diathesis. Bone marrow examination revealed high number of eosinophilic precursors (60%) among the total nucleated bone marrow cells. Cytogenetic study with G- banding method showed 46, XY, t (8;21)(q22;q22). The morphological abnormalities in eosinophils observed in AML suggested that eosinophils may be a part of leukemic process. PMID:21630067

  4. Eosinophilic colitis.

    PubMed

    Dion疄io de Sousa, Isabel Jos; Bonito, Nuno; Pais, Ana; Gerv嫳io, Helena

    2016-01-01

    A 57-year-old man, diagnosed with colon cancer stage III in July/2010, underwent surgery and received adjuvant chemotherapy with FOLFOX 4 (5-fluorouracil; calcium folinate and oxaliplatin), which ended in March/2011 after 12-cycles. It was then decided to maintain periodical surveillance. About 1?year later, the patient developed several episodes of diarrhoea, mainly during the night, and presented persistent peripheral eosinophilia in the blood count (range 585-1300 eosinophils/無). Colonoscopy was performed, with the histological result showing eosinophilic infiltration of the colon, compatible with eosinophilic colitis. The patient was treated with a short course of budesonide, achieving resolution of symptoms, and has remained asymptomatic. PMID:26957036

  5. Eosinophilic esophagitis

    PubMed Central

    Merves, Jamie; Muir, Amanda; Chandramouleeswaran, Prasanna Modayur; Cianferoni, Antonella; Wang, Mei-Lun; Spergel, Jonathan M.

    2015-01-01

    Objective To review the understanding of the pathogenesis of eosinophilic esophagitis (EoE) and the role of the immune system in the disease process. Data Sources Peer-reviewed articles on EoE from PubMed searching for Eosinophilic Esophagitis and fibrosis in the period of 1995 to 2013. Study Selection Studies on the clinical and immunologic features, pathogenesis, and management of EoE. Results Recent work has revealed that thymic stromal lymphopoietin and basophil have an increased role in the pathogenesis of disease. Additional understanding on the role of fibrosis in EoE is emerging. Conclusion The incidence of EoE is increasing like most atopic disease. Similar to other allergic diseases, EoE is treated with topical steroids and/or allergen avoidance. PMID:24566295

  6. Eosinophilic Lung Disorders

    MedlinePLUS

    ... You are here: Health Information > Condition Information Eosinophilic Lung Disorders Eosinophilic lung disorders are a category of ... of Programs and Services Doctors Who Treat Eosinophilic Lung Disorders Rohit K. Katial Rafeul Alam Joshua J. ...

  7. 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

  8. Induction of eosinophil apoptosis by hydrogen peroxide promotes the resolution of allergic inflammation.

    PubMed

    Reis, A C; Alessandri, A L; Athayde, R M; Perez, D A; Vago, J P; vila, T V; Ferreira, T P T; de Arantes, A C S; Coutinho, D de S獺; Rachid, M A; Sousa, L P; Martins, M A; Menezes, G B; Rossi, A G; Teixeira, M M; Pinho, V

    2015-01-01

    Eosinophils are effector cells that have an important role in the pathogenesis of allergic disease. Defective removal of these cells likely leads to chronic inflammatory diseases such as asthma. Thus, there is great interest in understanding the mechanisms responsible for the elimination of eosinophils from inflammatory sites. Previous studies have demonstrated a role for certain mediators and molecular pathways responsible for the survival and death of leukocytes at sites of inflammation. Reactive oxygen species have been described as proinflammatory mediators but their role in the resolution phase of inflammation is poorly understood. The aim of this study was to investigate the effect of reactive oxygen species in the resolution of allergic inflammatory responses. An eosinophilic cell line (Eol-1) was treated with hydrogen peroxide and apoptosis was measured. Allergic inflammation was induced in ovalbumin sensitized and challenged mouse models and reactive oxygen species were administered at the peak of inflammatory cell infiltrate. Inflammatory cell numbers, cytokine and chemokine levels, mucus production, inflammatory cell apoptosis and peribronchiolar matrix deposition was quantified in the lungs. Resistance and elastance were measured at baseline and after aerosolized methacholine. Hydrogen peroxide accelerates resolution of airway inflammation by induction of caspase-dependent apoptosis of eosinophils and decrease remodeling, mucus deposition, inflammatory cytokine production and airway hyperreactivity. Moreover, the inhibition of reactive oxygen species production by apocynin or in gp91(phox-/-) mice prolonged the inflammatory response. Hydrogen peroxide induces Eol-1 apoptosis in vitro and enhances the resolution of inflammation and improves lung function in vivo by inducing caspase-dependent apoptosis of eosinophils. PMID:25675292

  9. Induction of eosinophil apoptosis by hydrogen peroxide promotes the resolution of allergic inflammation

    PubMed Central

    Reis, A C; Alessandri, A L; Athayde, R M; Perez, D A; Vago, J P; vila, T V; Ferreira, T P T; de Arantes, A CS; de S獺 Coutinho, D; Rachid, M A; Sousa, L P; Martins, M A; Menezes, G B; Rossi, A G; Teixeira, M M; Pinho, V

    2015-01-01

    Eosinophils are effector cells that have an important role in the pathogenesis of allergic disease. Defective removal of these cells likely leads to chronic inflammatory diseases such as asthma. Thus, there is great interest in understanding the mechanisms responsible for the elimination of eosinophils from inflammatory sites. Previous studies have demonstrated a role for certain mediators and molecular pathways responsible for the survival and death of leukocytes at sites of inflammation. Reactive oxygen species have been described as proinflammatory mediators but their role in the resolution phase of inflammation is poorly understood. The aim of this study was to investigate the effect of reactive oxygen species in the resolution of allergic inflammatory responses. An eosinophilic cell line (Eol-1) was treated with hydrogen peroxide and apoptosis was measured. Allergic inflammation was induced in ovalbumin sensitized and challenged mouse models and reactive oxygen species were administered at the peak of inflammatory cell infiltrate. Inflammatory cell numbers, cytokine and chemokine levels, mucus production, inflammatory cell apoptosis and peribronchiolar matrix deposition was quantified in the lungs. Resistance and elastance were measured at baseline and after aerosolized methacholine. Hydrogen peroxide accelerates resolution of airway inflammation by induction of caspase-dependent apoptosis of eosinophils and decrease remodeling, mucus deposition, inflammatory cytokine production and airway hyperreactivity. Moreover, the inhibition of reactive oxygen species production by apocynin or in gp91phox/ mice prolonged the inflammatory response. Hydrogen peroxide induces Eol-1 apoptosis in vitro and enhances the resolution of inflammation and improves lung function in vivo by inducing caspase-dependent apoptosis of eosinophils. PMID:25675292

  10. 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

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

    ClinicalTrials.gov

    2015-11-16

    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

  12. Leukemia

    MedlinePLUS

    ... at a Glance Show More At a Glance Estimated New Cases in 2015 54,270 % of All New Cancer Cases 3.3% Estimated Deaths in 2015 24,450 % of All Cancer ... of This Cancer : In 2012, there were an estimated 318,389 people living with leukemia in the ...

  13. 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

  14. 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

  15. 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

  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. 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

  18. 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

  19. 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

  20. 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

  1. Pseudotumoral Eosinophilic Cystitis

    PubMed Central

    Saadi, Ahmed; Bouzouita, Abderrazak; Ayed, Haroun; Kerkeni, Walid; Cherif, Mohamed; Ben Slama, Riadh M.; Derouiche, Amine; Chebil, Mohamed

    2015-01-01

    Eosinophilic cystitis is a rare inflammatory disease of the bladder which origin and pathogenesis are unknown. Since the first description in 1960, hundreds of cases have been reported, 20 Pseudotumor forms. We report a case of cystitis eosinophils in tumor-form, a patient of 72 years without urological or allergic history. The patient was treated with endoscopic resection alone. The outcome was favorable with disappearance symptoms and no recurrence at 1, 3 and 6 months controls. We carry a literature review of cystitis eosinophils on the different clinical manifestations, the means diagnostic and therapeutic modalities.

  2. 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

  3. P2Y12 antagonist attenuates eosinophilic inflammation and airway hyperresponsiveness in a mouse model of asthma.

    PubMed

    Suh, Dong-Hyeon; Trinh, Hoang Kim Tu; Liu, Jing-Nan; Pham, Le Duy; Park, Sang Myun; Park, Hae-Sim; Shin, Yoo Seob

    2016-02-01

    Leukotriene E4 (LTE4) that plays a key role in airway inflammation is expressed on platelets and eosinophils. We investigated whether blocking of the P2Y12 receptor can suppress eosinophilic inflammation in a mouse model of asthma because platelets and eosinophils share this receptor to be activated. BALB/c mice were sensitized by intraperitoneal injection of ovalbumin (OVA), followed by OVA nebulization. On each challenge day, clopidogrel, a P2Y12 antagonist was administered 30 min. before each challenge. Forty-eight hours after the last OVA challenge, mice were assessed for airway hyperresponsiveness (AHR), cell composition and cytokine levels, including chemokine ligand 5 (CCL5), in bronchoalveolar lavage (BAL) fluid. EOL cells were treated with LTE4, with or without clopidogrel treatment, and intracellular and extracellular eosinophil cationic protein (ECP) expressions were measured to find the inhibiting function of P2Y12 antagonist on eosinophilic activation. The levels of P2Y12 expression were increased markedly in the lung homogenates of OVA-sensitized and -challenged mice after platelet depletion. Administration of clopidogrel decreased AHR and the number of airway inflammatory cells, including eosinophils, in BAL fluid following OVA challenge. These results were associated with decreased levels of Th2 cytokines and CCL5. Histological examination showed that inflammatory cells as well as mucus-containing goblet cells were reduced in clopidogrel-administered mice compared to vehicle-treated mice. Clopidogrel inhibited extracellular ECP secretion after LTE4 stimulation in EOL-1 cells. Clopidogrel could prevent development of AHR and airway inflammation in a mouse model of asthma. P2Y12 can be a novel therapeutic target to the suppression of eosinophils in asthma. PMID:26612496

  4. Eosinophilic Gastrointestinal Disorders

    MedlinePLUS

    ... affects both the stomach and small intestine. Eosinophilic colitis, which affects the colon, or large intestine. In ... drink enough of the formula to maintain proper nutrition and may require tube feedings directly into the ...

  5. Eosinophilic gastroenteritis: an update.

    PubMed

    Lucendo, Alfredo J; Arias, Angel

    2012-09-01

    Eosinophilic gastroenteritis (EGE) is characterized by dense eosinophilic inflammation of one or several digestive tract sections. The symptoms include abdominal pain, weight loss, vomiting and diarrhea. Biopsy samples taken during endoscopic examination allows the diagnosis of the disease. An infiltration of >30 eosinophils per high-power field in at least five high-power fields, exhibiting signs of eosinophilic degranulation and extending to the muscularis mucosa or submucosa are all histological indications of EGE. EGE is traditionally classified into three forms depending on the depth of inflammation in the wall (mucosal, muscular or serosal). This, together with the digestive tract segments involved, determines the clinical presentation. The natural history of EGE includes three different evolutionary patterns, since patients may suffer a single outbreak, a recurrent course or even chronic disease. Corticosteroids are the most frequently used therapy for EGE; dietary treatments should be also considered. Surgery has been limited to solving obstruction and small bowel perforation. PMID:23061710

  6. The Eosinophil in Infection.

    PubMed

    Ravin, Karen A; Loy, Michael

    2016-04-01

    First described by Paul Ehrlich in 1879, who noted its characteristic staining by acidophilic dyes, for many years, the eosinophil was considered to be an end-effector cell associated with helminth infections and a cause of tissue damage. Over the past 30years, research has helped to elucidate the complexity of the eosinophil's function and establish its role in host defense and immunity. Eosinophils express an array of ligand receptors which play a role in cell growth, adhesion, chemotaxis, degranulation, and cell-to-cell interactions. They play a role in activation of complement via both classical and alternative pathways. Eosinophils synthesize, store and secrete cytokines, chemokines, and growth factors. They can process antigen, stimulate T cells, and promote humoral responses by interacting with B cells. Eosinophils can function as antigen presenting cells and can regulate processes associated with both T1 and T2 immunity. Although long known to play a role in defense against helminth organisms, the interactions of eosinophils with these parasites are now recognized to be much more complex. In addition, their interaction with other pathogens continues to be investigated. In this paper, we review the eosinophil's unique biology and structure, including its characteristic granules and the effects of its proteins, our developing understanding of its role in innate and adaptive immunity and importance in immunomodulation, and the part it plays in defense against parasitic, viral, fungal and bacterial infections. Rather than our worst enemy, the eosinophil may, in fact, be one of the most essential components in host defense and immunity. PMID:26690368

  7. Eosinophils in glioblastoma biology

    PubMed Central

    2012-01-01

    Glioblastoma multiforme (GBM) is the most common primary brain tumor in adults. The development of this malignant glial lesion involves a multi-faceted process that results in a loss of genetic or epigenetic gene control, un-regulated cell growth, and immune tolerance. Of interest, atopic diseases are characterized by a lack of immune tolerance and are inversely associated with glioma risk. One cell type that is an established effector cell in the pathobiology of atopic disease is the eosinophil. In response to various stimuli, the eosinophil is able to produce cytotoxic granules, neuromediators, and pro-inflammatory cytokines as well as pro-fibrotic and angiogenic factors involved in pathogen clearance and tissue remodeling and repair. These various biological properties reveal that the eosinophil is a key immunoregulatory cell capable of influencing the activity of both innate and adaptive immune responses. Of central importance to this report is the observation that eosinophil migration to the brain occurs in response to traumatic brain injury and following certain immunotherapeutic treatments for GBM. Although eosinophils have been identified in various central nervous system pathologies, and are known to operate in wound/repair and tumorstatic models, the potential roles of eosinophils in GBM development and the tumor immunological response are only beginning to be recognized and are therefore the subject of the present review. PMID:22251275

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

    ClinicalTrials.gov

    2016-03-16

    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

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

    ClinicalTrials.gov

    2016-02-17

    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

  10. 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

  11. 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

  12. Eosinophilic Liver Infiltration

    PubMed Central

    Figueroa Rivera, Ivonne; Toro, Doris H.; Gutierrez, Jose; Acosta, Eduardo

    2015-01-01

    Eosinophilic liver infiltration is a commonly encountered focal eosinophil-related inflammation with or without necrosis, which can be seen on computed tomography (CT) in the presence of peripheral eosinophilia. Although this entity has a relatively benign course, it is related to numerable conditions for which diagnosis may be challenging and requires substantial diagnostic work-up for proper management and care of the underlying disease. We report a case of a 60-year-old man who presented with a 1-week history of right upper quadrant abdominal pain with multiple ill-defined liver hypodensities associated with significant eosinophilia. PMID:26504883

  13. Eosinophilic Drug Allergy.

    PubMed

    Kuruvilla, Merin; Khan, David A

    2016-04-01

    While peripheral or tissue eosinophilia may certainly characterize drug eruptions, this feature is hardly pathognomonic for a medication-induced etiology. While delayed drug hypersensitivity reactions with prominent eosinophilic recruitment have been typically classified as type IVb reactions, their pathophysiology is now known to be more complex. Eosinophilic drug reactions have a diversity of presentations and may be benign and self-limited to severe and life-threatening. The extent of clinical involvement is also heterogeneous, ranging from isolated peripheral eosinophilia or single organ involvement (most often the skin and lung) to systemic disease affecting multiple organs, classically exemplified by drug-reaction with eosinophilia and systemic symptoms (DRESS). The spectrum of implicated medications in the causation of DRESS is ever expanding, and multiple factors including drug metabolites, specific HLA alleles, herpes viruses, and immune system activation have been implicated in pathogenesis. Due to this complex interplay of various factors, diagnostic workup in terms of skin and laboratory testing has not been validated. Similarly, the lack of controlled trials limits treatment options. This review also describes other localized as well as systemic manifestations of eosinophilic disease induced by various medication classes, including their individual pathophysiology, diagnosis, and management. Given the multitude of clinical patterns associated with eosinophilic drug allergy, the diagnosis can be challenging. Considerable deficits in our knowledge of these presentations remain, but the potential for severe reactions should be borne in mind in order to facilitate diagnosis and institute appropriate management. PMID:26006718

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

    ClinicalTrials.gov

    2015-12-04

    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. Eosinophilic Esophagitis and Gastroenteritis.

    PubMed

    Cianferoni, Antonella; Spergel, Jonathan M

    2015-09-01

    Eosinophilic gastrointestinal disease (EGID) can be classified as eosinophilic esophagitis (EoE) when the eosinophilia is limited to the esophagus or as eosinophilic gastritis (EG) if it is limited to the gastric tract, eosinophilic colitis (EC) if it is limited to the colon, and eosinophilic gastroenteritis (EGE) if the eosinophilia involves one or more parts of the gastrointestinal tract. EoE is by far the most common EGID. It is a well-defined chronic atopic disease due to a T helper type 2 (Th2) inflammation triggered often by food allergens. EoE diagnosis is done if an esophageal biopsy shows at least 15 eosinophils per high power field (eos/hpf). Globally accepted long-term therapies for EoE are the use of swallowed inhaled steroids or food antigen avoidance. The treatment of EoE is done not only to control symptoms but also to prevent complications such as esophageal stricture and food impaction. EGE cause non-specific gastrointestinal (GI) symptoms and are diagnosed if esophagogastroduodenoscopy (EGD)/colonoscopy show eosinophilia in one or more parts of the GI tract. They are rare diseases with an unclear pathogenesis, and they are poorly defined in terms of diagnostic criteria and treatment. Before initiating treatment of any EGE, it is imperative to conduct a differential diagnosis to exclude other causes of hypereosinophilia with GI localization. EGE are often poorly responsive to therapy and there is no commonly accepted long-term treatment. EG has many characteristics similar to EoE, including the fact that it is often due to a food allergen-driven Th2 inflammation; transcriptome analysis however shows that it is more a systemic disease and has a different gene signature than EoE. EC is a benign form of delayed food allergy in infant and is instead a difficult-to-treat severe inflammatory condition in older children and adults. EC in the latter groups can be a manifestation of drug allergy or autoimmune disease. Overall EGE, EC, and EG are rare and are a diagnosis of exclusion until more common causes of eosinophilia have been excluded. PMID:26233430

  17. Eosinophilic oesophagitis versus reflux oesophagitis.

    PubMed

    Ensari, A

    2011-06-01

    Reflux oesophagitis (RO) is defined as the inflammation of the lower oesophagus due to damage caused by acid reflux from the stomach. Histopathologic features of acid reflux include epithelial hyperplasia, baloon cells, basal cell hyperplasia, papillary elongation, dilated intercellular spaces representing epithelial oedema, vascular congestion, and inflammatory cell infiltration comprising lymphocytes, neutrophils and eosinophils, most of which are nonspecific. Eosinophils, on the other hand, are considered to be important in the differential diagnosis of RO and EoO which is a chronic inflammatory disorder characterized by eosinophil infiltration of the oesophageal mucosa associated with a history of atopy or allergy. A cut off value of more than 15 eosinophils per high power field is suggestive of EoO with a tendency of eosinophils to concentrate in the superficial parts of squamous mucosa just below the luminal surface where they tend to form eosinophilic microabsesses. Dense fibrosis is seen in up to one-third of the patients with EoO together with an increase in the number of eosinophils in the lamina propria. In patients with intermediate levels of eosinophil counts (7-15 eos/hpf) immunohistochemistry for eosinophil secretory products could prove useful as it highlights degranulated eosinophils. In conclusion, distinguishing EoO from RO requires a thorough clinical, endoscopic and histologic evaluation of the patient which can only be achieved when close communication between pathologist and gastroenterologist is established. PMID:21861318

  18. Eosinophilic gastroenteritis with eosinophilic ascites: report of a case.

    PubMed

    Tai, Y G; Liu, J D; Lin, K Y; Chang, J G; Wang, C K; Siauw, C P; Chen, P H

    1990-10-01

    Eosinophilic gastroenteritis is a relatively uncommon disease of unknown etiology. Eosinophilic ascites resulting from significant serosal involvement is the rarest clinical subtype. The case reported here is of a 30-year-old male presenting with abdominal pain, diarrhea, and ascites. His personal history included childhood asthma, allergic rhinitis, and recurrent urticaria. The clinical picture was characterized by peripheral eosinophilia and eosinophilic infiltrates of the stomach and small bowel. Computed tomogram (CT) of the abdomen showed generalized thickening of the gastric and small bowel wall. Paracentesis revealed exudative ascites rich in eosinophils. The patient experienced an impressive response to steroid therapy. PMID:1981780

  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. Eosinophilic myositis: an updated review.

    PubMed

    Selva-O'Callaghan, A; Trallero-Aragu嫳, E; Grau, J M

    2014-01-01

    Eosinophilia-associated myopathies are clinically and pathologically heterogeneous conditions characterized by the presence of peripheral and/or muscle eosinophilia. There are at least three distinct subtypes: focal eosinophilic myositis, eosinophilic polymyositis, and eosinophilic perimyositis. Infiltrating eosinophils are not always identified in conventional muscle histologic examination, but the eosinophil major basic protein, whose extracellular diffusion is considered a hallmark of eosinophilic cytotoxicity, is usually detected by immunostaining in muscle biopsy. Whereas focal eosinophilic myositis seems to be a benign and isolated condition, and perimyositis is usually related with the inflammatory infiltrate due to fasciitis, eosinophilic polymyositis can be associated with muscular dystrophy or be a feature of multiorgan hypereosinophilic syndrome. Muscle biopsy remains the cornerstone for the diagnosis. Parasitic infections, connective tissue disorders, hematologic and non-hematologic malignancies, drugs, and toxic substances are the main etiologic agents of eosinophilia-associated myopathy. However, in some cases, no known etiologic factor is identified, and these are considered idiopathic. Glucocorticoids are the mainstay therapy in idiopathic forms. Imatinib and mepolizumab, a humanized anti-interleukin 5 monoclonal antibody, may be useful in patients with eosinophilic myositis as part of a hypereosinophilic syndrome. PMID:24424174

  1. The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia.

    PubMed

    Wen, Ting; Mingler, Melissa K; Blanchard, Carine; Wahl, Benjamin; Pabst, Oliver; Rothenberg, Marc E

    2012-02-01

    CD22 is currently recognized as a B cell-specific Siglec and has been exploited therapeutically with humanized anti-CD22 mAb having been used against B cell leukemia. In this study, tissue-specific eosinophil mRNA microarray analysis identified that CD22 transcript levels of murine gastrointestinal (GI) eosinophils are 10-fold higher than those of lung eosinophils. To confirm the mRNA data at the protein level, we developed a FACS-based protocol designed to phenotype live GI eosinophils isolated from the murine lamina propria. Indeed, we found that jejunum eosinophils expressed remarkably high levels of surface CD22, similar to levels found in B cells across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity, and allergen-challenged lung. Eosinophils isolated from newborn mice did not express CD22 but subsequently upregulated CD22 expression to adult levels within the first 10 d after birth. The GI lamina propria from CD22 gene-targeted mice harbored more eosinophils than wild type control mice, whereas the GI eosinophil turnover rate was unaltered in the absence of CD22. Our findings identify a novel expression pattern and tissue eosinophilia-regulating function for the "B cell-specific" inhibitory molecule CD22 on GI eosinophils. PMID:22190185

  2. The pan-B cell marker CD22 is expressed on gastrointestinal eosinophils and negatively regulates tissue eosinophilia

    PubMed Central

    Wen, Ting; Mingler, Melissa K.; Blanchard, Carine; Wahl, Benjamin; Pabst, Oliver; Rothenberg, Marc E.

    2011-01-01

    CD22 is currently recognized as a B cell-specific Siglec and has been exploited therapeutically with humanized anti-CD22 monoclonal antibody having been used against B cell leukemia. Herein, tissue-specific eosinophil mRNA microarray analysis identified that CD22 transcript levels of murine gastrointestinal (GI) eosinophils are 10-fold higher than those of lung eosinophils. In order to confirm the mRNA data at the protein level, we developed a FACS-based protocol designed to phenotype live GI eosinophils isolated from the murine lamina propria. Indeed, we found that jejunum eosinophils expressed remarkably high levels of surface CD22, similar to levels found in B cells across multiple mouse strains. In contrast, CD22 was undetectable on eosinophils from the colon, blood, thymus, spleen, uterus, peritoneal cavity and allergen-challenged lung. Eosinophils isolated from newborn mice did not express CD22 but subsequently upregulated CD22 expression to adult levels within the first 10 days after birth. The GI lamina propria from CD22 gene-targeted mice harbored more eosinophils than wild-type control mice, while the GI eosinophil turnover rate was unaltered in the absence of CD22. Our findings identify a novel expression pattern and tissue eosinophilia-regulating function for the B cell-specific inhibitory molecule CD22 on GI eosinophils. PMID:22190185

  3. 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

  4. Pachydermatous eosinophilic dermatitis.

    PubMed

    Salomon, Joanna; Bia?ynicki-Birula, Rafa?; Wo?niak, Zdzis?aw; Baran, Eugeniusz

    2011-01-01

    A case is presented of a female Caucasian patient with chronic peripheral blood eosinophilia and unusual skin manifestations. Within a couple of years, the patient developed multiple hyperkeratotic and hyperpigmented papules and plaques all over the body, palmoplantar keratoderma, pachydermia of acral parts of the body, and generalized pruritus. Generalized lymphadenopathy appeared. Other relevant symptoms were persistent peripheral blood hypereosinophilia and increased level of total IgE. The patient was diagnosed with a very rare condition, pachydermatous eosinophilic dermatitis, and was administered combined therapy with dapsone, oral methylprednisolone and fexophenadine. After one month of treatment, the skin changes markedly improved. PMID:21489364

  5. PLAG (1-Palmitoyl-2-Linoleoyl-3-Acetyl-rac-Glycerol) Modulates Eosinophil Chemotaxis by Regulating CCL26 Expression from Epithelial Cells

    PubMed Central

    Jeong, Jinseon; Kim, Young-Jun; Yoon, Sun Young; Kim, Yong-Jae; Kim, Joo Heon; Sohn, Ki-Young; Kim, Heung-Jae; Han, Yong-Hae; Chong, Saeho; Kim, Jae Wha

    2016-01-01

    Increased number of eosinophils in the circulation and sputum is associated with the severity of asthma. The respiratory epithelium produces chemokine (C-C motif) ligands (CCL) which recruits and activates eosinophils. A chemically synthesized monoacetyl-diglyceride, PLAG (1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol) is a major constituent in the antlers of Sika deer (Cervus nippon Temminck) which has been used in oriental medicine. This study was aimed to investigate the molecular mechanism of PLAG effect on the alleviation of asthma phenotypes. A549, a human alveolar basal epithelial cell, and HaCaT, a human keratinocyte, were activated by the treatment of interleukin-4 (IL-4), and the expression of chemokines, known to be effective on the induction of eosinophil migration was analyzed by RT-PCR. The expression of IL-4 induced genes was modulated by the co-treatment of PLAG. Especially, CCL26 expression from the stimulated epithelial cells was significantly blocked by PLAG, which was confirmed by ELISA. The transcriptional activity of signal transducer and activator of transcription 6 (STAT6), activated by IL-4 mediated phosphorylation and nuclear translocation, was down-regulated by PLAG in a concentration-dependent manner. In ovalbumin-induced mouse model, the infiltration of immune cells into the respiratory tract was decreased by PLAG administration. Cytological analysis of the isolated bronchoalveolar lavage fluid (BALF) cells proved the infiltration of eosinophils was significantly reduced by PLAG. In addition, PLAG inhibited the migration of murine bone marrow-derived eosinophils, and human eosinophil cell line, EoL-1, which was induced by the addition of A549 culture medium. PMID:27010397

  6. Idiopathic chronic eosinophilic pneumonia

    PubMed Central

    Marchand, Eric; Cordier, Jean-Fran癟ois

    2006-01-01

    Idiopathic chronic eosinophilic pneumonia (ICEP) is characterized by subacute or chronic respiratory and general symptoms, alveolar and/or blood eosinophilia, and peripheral pulmonary infiltrates on chest imaging. Eosinophilia is present in most cases, usually in excess of 1000/mm3. In absence of significant blood eosinophilia, a diagnosis of ICEP is supported by the demonstration of bronchoalveolar lavage eosinophilia. ICEP is typically associated with eosinophil counts higher than lymphocyte counts in the bronchoalveolar lavage. ICEP is a rare disorder of unknown cause. Its exact prevalence remains unknown. ICEP may affect every age group but is rare in childhood. It is twice as frequent in women as in men. One third to one half of the ICEP patients have a history of asthma. The mainstay of treatment of ICEP is systemic corticosteroids. Response to oral corticosteroid therapy is dramatic and has led to the consideration of corticosteroid challenge as a diagnostic test for ICEP. Nevertheless, relapses or development of severe asthma are frequent when tapering or withdrawing treatment. Long-term oral corticosteroid therapy is necessary in up to half of the patients. PMID:16722612

  7. 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

  8. Eosinophilic histiocytosis. Histopathology and immunohistochemistry.

    PubMed

    Helton, J L; Maize, J C

    1996-04-01

    We review the clinical features, histopathology, and immunohistochemistry in three cases of eosinophilic histiocytosis, comparing lymphomatoid papulosis and eosinophilic histiocytosis. Each of the patients presented with self-healing recurrent papules and ulcerative nodules that were associated with pruritus. Disease duration was 5 months to 9 years. Histologically, the lesions demonstrated spongiosis and lymphocytic exocytosis, epidermal hyperplasia, papillary dermal edema, and a superficial and deep mixed perivascular inflammatory infiltrate. The infiltrate showed numerous eosinophils, histiocytoid cells, lymphocytes, and large mononuclear cells with atypical hyperchromatic nuclei. Most of the lymphocytes and large mononuclear cells with atypical nuclei marked with UCHL-1 (T-cell marker). The histiocytoid cells marked with S-100 and were dendritic both in the epidermis and the dermis. Eosinophilic histiocytosis appears to differ from classic lymphomatoid papulosis. It presents with recurrent papules and nodules associated with marked pruritus. Eosinophilic histiocytosis uniformly has more eosinophils and does not have the Reed-Sternberg cells often observed in lymphomatoid papulosis type A. Eosinophilic histiocytosis does not have cells that mark with Ki-1 and shows numerous S-100-positive histiocytoid cells that are most likely Langerhans cells, unlike lymphomatoid papulosis. However, eosinophilic histiocytosis may be an unusual Ki-1-negative variant of lymphomatoid papulosis with histopathologic changes not typical of type A or type B. In addition, eosinophilic histiocytosis lacks multinucleated histiocytes and the atypical histiocyte with a reniform nucleus, findings that are characteristic of histiocytosis X. Further studies are needed to define the pathophysiology and prognosis of this apparently distinct entity more accurately. PMID:8739984

  9. MK2206 in Treating Younger Patients With Recurrent or Refractory Solid Tumors or Leukemia

    ClinicalTrials.gov

    2014-04-28

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Leukemias of Ambiguous Lineage; Acute Myeloid Leukemia/Transient Myeloproliferative Disorder; Acute Undifferentiated Leukemia; Aggressive NK-cell Leukemia; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blastic Phase Chronic Myelogenous Leukemia; Blastic Plasmacytoid Dendritic Cell Neoplasm; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Grade III Lymphomatoid Granulomatosis; Childhood Immunoblastic Large Cell Lymphoma; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Mast Cell Leukemia; Myeloid/NK-cell Acute Leukemia; Noncutaneous Extranodal Lymphoma; Post-transplant Lymphoproliferative Disorder; Primary Central Nervous System Hodgkin Lymphoma; Primary Central Nervous System Non-Hodgkin Lymphoma; Progressive Hairy Cell Leukemia, Initial Treatment; Prolymphocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma; Recurrent Grade 3 Follicular Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Marginal Zone Lymphoma; Recurrent Mycosis Fungoides/Sezary Syndrome; Recurrent Small Lymphocytic Lymphoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Hairy Cell Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Small Intestine Lymphoma; Splenic Marginal Zone Lymphoma; Unspecified Childhood Solid Tumor, Protocol Specific; Waldenstr繹m Macroglobulinemia

  10. EoE (Eosinophilic Esophagitis)

    MedlinePLUS

    ... Cincinnati Center for Eosinophilic Disorders CCFA- Crohns and Colitis Foundation of America CDF- Celiac Disease Foundation Childrens ... North American Society for Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) American Society for Gastrointestinal Endoscopy (ASGE) National ...

  11. Eosinophil autofluorescence and its use in isolation and analysis of human eosinophils using flow microfluorometry

    SciTech Connect

    Weil, G.J.; Chused, T.M.

    1981-06-01

    Unstained human eosinophils exhibit unusually bright autofluorescence, which allows them to be distinguished from other leukocytes using fluorescence microscopy. Eosinophil fluorescence is associated with the cytoplasmic granules of the cells. Eosinophil granule extracts, containing an as-yet-undefined eosinophil fluorescence factor, exhibited excitation maxima at 370 nm and 450 nm, with maximum emission at 520 nm. Eosinophils adhering to opsonized parasites in vitro deposit fluorescent material onto the parasite surface. Eosinophil fluorescence was of sufficient intensity to allow the preparation of viable, highly enriched (greater than or equal to 98%), eosinophil suspensions from peripheral blood of normal and eosinophilic donors using a fluorescence-activated cell sorter. Quantitative studies of eosinophil autofluorescence were performed using flow microfluorometry. Fluorescence intensity of blood eosinophils from normal volunteers and eosinophilic patients varied inversely with the log of the donor's absolute eosinophil count regardless of clinical diagnosis.

  12. Segregation of eosinophil proteins in alveolar macrophage compartments in chronic eosinophilic pneumonia.

    PubMed Central

    Janin, A; Torpier, G; Courtin, P; Capron, M; Prin, L; Tonnel, A B; Hatron, P Y; Gosselin, B

    1993-01-01

    BACKGROUND: The objective was to characterise the process and consequences of eosinophil activation and lysis in patients with chronic eosinophilic pneumonia and to compare them with those in patients with eosinophil pulmonary infiltrates from other causes. METHODS: Cells from bronchoalveolar lavage fluid of four patients with chronic eosinophilic pneumonia and four patients with eosinophilic infiltrates associated with Sj鐷ren's syndrome, drug hypersensitivity pneumonia, postradiotherapy fibrosis, and pulmonary disease associated with graft versus host disease were studied ultrastructurally and with immunogold labelled antibodies directed against eosinophil proteins: major basic protein, eosinophil cationic protein, and Charcot-Leyden crystal protein. The concentration of eosinophil cationic protein was also measured in bronchoalveolar fluid. RESULTS: In the four patients with chronic eosinophilic pneumonia, ultrastructural studies demonstrated numerous lysed eosinophils. Further, three released eosinophil proteins were detected in distinct cytoplasmic structures in alveolar macrophages. These features were not found in the four patients with eosinophilic pulmonary infiltrates from other causes. CONCLUSION: Eosinophils in chronic eosinophilic pneumonia show signs of activation with release of eosinophil proteins. The appearance of three of these eosinophil proteins in different macrophage compartments suggests that macrophage uptake, with or without intracellular transport of released eosinophil proteins, involves separate mechanisms. This interaction does not lead to macrophage lysis, however, and one or more of these eosinophil proteins might directly affect macrophage function. Images PMID:8434356

  13. Biomarkers of eosinophilic inflammation in asthma.

    PubMed

    Loutsios, Chrystalla; Farahi, Neda; Porter, Linsey; Lok, Laurence S C; Peters, A Michael; Condliffe, Alison M; Chilvers, Edwin R

    2014-04-01

    Eosinophils are mediators of allergic inflammation and are implicated in the pathogenesis of numerous conditions including asthma, parasitic infections, neoplasms, hyper-eosinophilic syndromes, vasculitic disorders, and organ-specific conditions. Assessing eosinophilic inflammation is therefore important in establishing a diagnosis, in monitoring and assessing response to treatment, and in testing novel therapeutics. Clinical markers of atopy and eosinophilic inflammation include indirect tests such as lung function, exhaled breath condensate analysis, fractional exhaled nitric oxide, serum immunoglobulin E levels and serum periostin. Direct measures, which quantify but do not anatomically localise inflammation include blood eosinophil counts, serum or plasma eosinophil cationic protein and sputum eosinophil levels. Cytology from bronchoalveolar lavage and histology from endobronchial and transbronchial biopsies are better at localising inflammation but are more invasive. Novel approaches using radiolabelled eosinophils with single-photon emission computed tomography, offer the prospect of non-invasive methods to localise eosinophilic inflammation. PMID:24460178

  14. Targeting Eosinophils in Allergy, Inflammation and Beyond

    PubMed Central

    Fulkerson, Patricia C.; Rothenberg, Marc E.

    2013-01-01

    Eosinophils can regulate local immune and inflammatory responses, and their accumulation in the blood and tissue is associated with several inflammatory and infectious diseases. As such, therapies aimed at eosinophils may help control diverse diseases, including atopic disorders such as asthma and allergy, and diseases not primarily associated with eosinophils such as autoimmunity and malignancy. Recently, eosinophil-targeted therapeutic agents aimed at blocking specific steps involved in eosinophil development, migration and activation have entered clinical testing and have produced encouraging results and insights into the role of eosinophils. Herein, we describe recent advances in the development of first generation eosinophil-targeted therapies and highlight strategies for using personalized medicine approaches for eosinophilic disorders. PMID:23334207

  15. Allergic Mechanisms in Eosinophilic Esophagitis

    PubMed Central

    Wechsler, Joshua B; Bryce, Paul J

    2014-01-01

    Paralleling the overall trend in allergic diseases, Eosinophilic Esophagitis is rapidly increasing in incidence. It is associated with food antigen-triggered, eosinophil-predominant inflammation and the pathogenic mechanisms have many similarities to other chronic atopic diseases, such as eczema and allergic asthma. Studies in animal models and from patients over the last 15 years have suggested that allergic sensitization leads to food-specific IgE and T-helper lymphocyte type 2 cells, both of which appear to contribute to the pathogenesis along with basophils, mast cells, and antigen-presenting cells. This review will outline our current understandings of the allergic mechanisms that drive eosinophilic esophagitis, drawing from clinical and translational studies in humans as well as experimental animal models. PMID:24813516

  16. Atypical presentations of eosinophilic fasciitis.

    PubMed

    Ergun, Tulin; Seckin, Dilek; Salman, Andac; Ocak, Esra Sarac; Yucelten, Ayse Deniz; Direskeneli, Haner; Demirkesen, Cuyan; Ekinci, Gazanfer; Bayik, Mahmut

    2016-01-01

    Eosinophilic fasciitis is an uncommon connective tissue disease that may mimic and overlap with other sclerosing disorders such as morphea and lichen sclerosus. Herein, we report four patients (two men and two women, aged 16-64 yeas) with eosinophilic fasciitis. There was overlap with both morphea and lichen sclerosus in 2 patients and with morphoea alone in 1 patient. Magnetic resonance imaging (MRI) was used for diagnosis in three patients and for assessing treatment response in one patient. Eosinophilic fasciitis may co-exist with morhoea and lichen sclerosus. In view of the overlapping clinical and histopathological features of these disorders, MRI may be helful in delineating the conditions by detecting involvement of fascia. PMID:26728810

  17. A review of eosinophilic gastroenteritis.

    PubMed Central

    Baig, Muhammad Ahsan; Qadir, Abdul; Rasheed, Javeria

    2006-01-01

    Eosinophilic gastroenteritis (EG) is a rare disease of unknown etiology characterized by patchy or diffuse eosinophilic infiltration of the gastrointestinal tract wall with various gastrointestinal manifestations. As clinical presentation and radiological findings in EG are nonspecific, diagnosis requires a high index of suspicion and exclusion of other disorders that are associated with peripheral eosinophilia. This article reviews the history, current concepts of this complex disorder and the common symptoms. Because there is no gold standard for this disease, a wide variety of diagnostic criteria is presented. Images Figure 1 PMID:17052051

  18. Human eosinophils express functional interleukin 2 receptors.

    PubMed Central

    Rand, T H; Silberstein, D S; Kornfeld, H; Weller, P F

    1991-01-01

    Because T cell-derived cytokines may affect the functioning of eosinophils, we have investigated the capacity of human eosinophils to respond to IL-2. IL-2 was a potent chemoattractant with ED50 of 10(-12) M with eosinophils from all normal and eosinophilic donors tested. The monoclonal antibodies anti-Tac and TU27 against p55 (Tac/CD25) and p75 receptor subunits, respectively, each inhibited IL-2-dependent eosinophil migration. The molar potency of IL-2 and the inhibitory activity of each of the above antibodies suggest that high affinity heterodimeric IL-2 receptor complexes mediated the migration responses of eosinophils to IL-2. Binding of monoclonal antibody against p75 was not detectable by flow cytometry, and high affinity binding sites for 125I-IL-2 were below the limits of quantitation on eosinophils from individuals with eosinophilia. Expression of p55 (Tac/CD25) by eosinophils, without requirement for in vitro activation, was demonstrable by flow cytometry, radioimmunoprecipitation, and Northern blotting for mRNA. Surface expression of p55 on eosinophils from normal or eosinophilic individuals increased during culture for 24-48 h with a biologic activity purified from stimulated U937 cells and to a lesser extent with granulocyte-macrophage CSF or lymphocyte chemoattractant factor but not with nine other cytokines. These studies indicate that blood eosinophils respond to IL-2 and identify one mechanism whereby activation of T lymphocytes may influence the function of eosinophils. Images PMID:1885772

  19. Eosinophil Granule Proteins: Form and Function

    PubMed Central

    Acharya, K. Ravi; Ackerman, Steven J.

    2014-01-01

    Experimental and clinical data strongly support a role for the eosinophil in the pathogenesis of asthma, allergic and parasitic diseases, and hypereosinophilic syndromes, in addition to more recently identified immunomodulatory roles in shaping innate host defense, adaptive immunity, tissue repair/remodeling, and maintenance of normal tissue homeostasis. A seminal finding was the dependence of allergic airway inflammation on eosinophil-induced recruitment of Th2-polarized effector T-cells to the lung, providing a missing link between these innate immune effectors (eosinophils) and adaptive T-cell responses. Eosinophils come equipped with preformed enzymatic and nonenzymatic cationic proteins, stored in and selectively secreted from their large secondary (specific) granules. These proteins contribute to the functions of the eosinophil in airway inflammation, tissue damage, and remodeling in the asthmatic diathesis. Studies using eosinophil-deficient mouse models, including eosinophil-derived granule protein double knock-out mice (major basic protein-1/eosinophil peroxidase dual gene deletion) show that eosinophils are required for all major hallmarks of asthma pathophysiology: airway epithelial damage and hyperreactivity, and airway remodeling including smooth muscle hyperplasia and subepithelial fibrosis. Here we review key molecular aspects of these eosinophil-derived granule proteins in terms of structure-function relationships to advance understanding of their roles in eosinophil cell biology, molecular biology, and immunobiology in health and disease. PMID:24802755

  20. Eosinophilic Gastritis Presenting as Tissue Necrosis.

    PubMed

    Jo, Yong Min; Jang, Jin Seok; Han, Seung Hee; Kang, Sang Hyun; Kim, Woo Jae; Jeong, Jin Sook

    2015-11-01

    Eosinophilic gastroenteritis is very rare disorder that is characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of any definite causes of eosinophilia. It is associated with various clinical gastrointestinal manifestations, and depends on the involved layer and site. We report a case of eosinophilic gastritis presenting with severe necrosis. The symptoms disappeared immediately after beginning steroid treatment, and the eosinophil count decreased to the reference range. The patient showed eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis. It is a unique presentation of eosinophilic gastritis. To the best of our knowledge, no case of eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis has been previously reported in Korea. PMID:26668805

  1. Eosinophilic Gastritis Presenting as Tissue Necrosis

    PubMed Central

    Jo, Yong Min; Jang, Jin Seok; Han, Seung Hee; Kang, Sang Hyun; Kim, Woo Jae; Jeong, Jin Sook

    2015-01-01

    Eosinophilic gastroenteritis is very rare disorder that is characterized by eosinophilic infiltration of the gastrointestinal tract in the absence of any definite causes of eosinophilia. It is associated with various clinical gastrointestinal manifestations, and depends on the involved layer and site. We report a case of eosinophilic gastritis presenting with severe necrosis. The symptoms disappeared immediately after beginning steroid treatment, and the eosinophil count decreased to the reference range. The patient showed eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis. It is a unique presentation of eosinophilic gastritis. To the best of our knowledge, no case of eosinophilic gastritis characterized by necrotic change such as necrotizing gastritis has been previously reported in Korea. PMID:26668805

  2. Eosinophilic gastroenteritis: ultrastructural evidence for a selective release of eosinophil major basic protein.

    PubMed Central

    Torpier, G; Colombel, J F; Mathieu-Chandelier, C; Capron, M; Dessaint, J P; Cortot, A; Paris, J C; Capron, A

    1988-01-01

    Ultrastructural study of mucosal eosinophils in a case of eosinophilic gastroenteritis involving stomach, duodenum and ileum showed an altered structure in ulcerated duodenal areas. The electron core density of eosinophil granules was inverted or disappeared and tubulovesicular structures occurred. Using immunogold staining with specific antibodies, major basic protein was detected diffusely in the matrix of eosinophil granules and out of the granules in tight association with extragranular membrane formations. In contrast, eosinophil cationic protein and eosinophil peroxidase were normally distributed in the granule matrix. When compared with the eosinophils in macroscopically normal duodenal mucosa in the same patient, these changes support a role for major basic protein in tissue damage in eosinophilic gastroenteritis. The diffusion of one granule protein from the granules to the exterior of the cells favours the view of a selective release of eosinophil mediators. Images Fig. 1 Fig. 2 PMID:3233790

  3. Eosinophilic Skin Diseases: A Comprehensive Review.

    PubMed

    Long, Hai; Zhang, Guiying; Wang, Ling; Lu, Qianjin

    2016-04-01

    Eosinophilic skin diseases, commonly termed as eosinophilic dermatoses, refer to a broad spectrum of skin diseases characterized by eosinophil infiltration and/or degranulation in skin lesions, with or without blood eosinophilia. The majority of eosinophilic dermatoses lie in the allergy-related group, including allergic drug eruption, urticaria, allergic contact dermatitis, atopic dermatitis, and eczema. Parasitic infestations, arthropod bites, and autoimmune blistering skin diseases such as bullous pemphigoid, are also common. Besides these, there are several rare types of eosinophilic dermatoses with unknown origin, in which eosinophil infiltration is a central component and affects specific tissue layers or adnexal structures of the skin, such as the dermis, subcutaneous fat, fascia, follicles, and cutaneous vessels. Some typical examples are eosinophilic cellulitis, granuloma faciale, eosinophilic pustular folliculitis, recurrent cutaneous eosinophilic vasculitis, and eosinophilic fasciitis. Although tissue eosinophilia is a common feature shared by these disorders, their clinical and pathological properties differ dramatically. Among these rare entities, eosinophilic pustular folliculitis may be associated with human immunodeficiency virus (HIV) infection or malignancies, and some other diseases, like eosinophilic fasciitis and eosinophilic cellulitis, may be associated with an underlying hematological disorder, while others are considered idiopathic. However, for most of these rare eosinophilic dermatoses, the causes and the pathogenic mechanisms remain largely unknown, and systemic, high-quality clinical investigations are needed for advances in better strategies for clinical diagnosis and treatment. Here, we present a comprehensive review on the etiology, pathogenesis, clinical features, and management of these rare entities, with an emphasis on recent advances and current consensus. PMID:25876839

  4. Dyspnea on daptomycin: eosinophilic pneumonia.

    PubMed

    Wojtaszczyk, Ann; Jankowich, Matthew

    2015-06-01

    We present a case of drug-induced acute eosinophilic pneumonia with characteristic imaging and bronchioloaveolar lavage (BAL) findings. Although not a common diagnosis, it is important to consider in the right clinical scenario, including a patient with presumed pneumonia that does not respond to typical treatment. Diagnosis is confirmed by bronchoscopy with BAL. For drug-induced types, treatment includes removal of the offending agent. Corticosteroids are used if symptoms are severe and can result in rapid clinical improvement. PMID:26020264

  5. A Case of Eosinophilic Gastroenteritis with Ascites

    PubMed Central

    Caglar, Erkan; Sezgin Caglar, Asl覺; Gokturk, Suut; Dobrucali, Ahmet

    2015-01-01

    Eosinophilic gastroenteritis is a rare disorder of unknown cause characterized by focal or diffuse eosinophilic infiltration of gastrointestinal tract, especially the stomach and duodenum. Its clinical presentation depends on which segment of gastrointestinal tract is affected and on the depth of eosinophilic infiltration in the affected segment. We present a case of a 35-year-old male with abdominal distention for six months. Laboratory testing revealed elevated eosinophil count and serum immunoglobulin E (IgE) levels. In abdominal tomography, ascites was observed, and eosinophilic infiltration was detected in duodenum biopsy samples, collected during endoscopic examination of upper gastrointestinal system. Clinical and pathologic findings of the patient responded to steroid dramatically. Even though their comorbidity is rare, eosinophilic gastroenteritis should be considered in differential diagnosis of patients with unspecified ascites. PMID:26819619

  6. Eosinophilic Jejunitis Presenting as Intractable Abdominal Pain

    PubMed Central

    Mungan, Zeynel; Attila, Tan; Kapran, Yersu; Tokatli, Ilyas Pinar; Unal, Zeynep

    2014-01-01

    Eosinophilic gastroenteritis is an uncommon disease characterized by eosinophilic infiltration of the gastrointestinal tract. The clinical manifestations are related to the layer(s) and extent of the bowel involved. In this paper, we present a case of intractable abdominal pain caused by jejunal submucosal eosinophilic infiltration without mucosal involvement, diagnosed by deep endoscopic biopsies. The patient was successfully treated with steroids without need for surgery for diagnosis or therapy. PMID:25565932

  7. Diagnostic Biomarkers in Eosinophilic Renal Neoplasms.

    PubMed

    Khor, Li Yan; Tan, Puay Hoon

    2016-02-01

    Incidental small renal masses identified on imaging are increasingly investigated via needle core or fine needle aspiration biopsies with limited material provided for rendering a diagnosis. Lesions with a prominent eosinophilic or oncocytic cell presence showing morphologic overlap between well-known eosinophilic neoplasms are challenging to diagnose. We review the range of known benign and malignant eosinophilic renal neoplasms and their immunoprofiles to elucidate a useful panel of stains that may assist the pathologist in making an accurate diagnosis. PMID:26614031

  8. Eosinophil secretion of granule-derived cytokines.

    PubMed

    Spencer, Lisa A; Bonjour, Kennedy; Melo, Rossana C N; Weller, Peter F

    2014-01-01

    Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration, and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here, we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines. PMID:25386174

  9. Eosinophil Secretion of Granule-Derived Cytokines

    PubMed Central

    Spencer, Lisa A.; Bonjour, Kennedy; Melo, Rossana C. N.; Weller, Peter F.

    2014-01-01

    Eosinophils are tissue-dwelling leukocytes, present in the thymus, and gastrointestinal and genitourinary tracts of healthy individuals at baseline, and recruited, often in large numbers, to allergic inflammatory foci and sites of active tissue repair. The biological significance of eosinophils is vast and varied. In health, eosinophils support uterine and mammary gland development, and maintain bone marrow plasma cells and adipose tissue alternatively activated macrophages, while in response to tissue insult eosinophils function as inflammatory effector cells, and, in the wake of an inflammatory response, promote tissue regeneration, and wound healing. One common mechanism driving many of the diverse eosinophil functions is the regulated and differential secretion of a vast array of eosinophil-derived cytokines. Eosinophils are distinguished from most other leukocytes in that many, if not all, of the over three dozen eosinophil-derived cytokines are pre-synthesized and stored within intracellular granules, poised for very rapid, stimulus-induced secretion. Eosinophils engaged in cytokine secretion in situ utilize distinct pathways of cytokine release that include classical exocytosis, whereby granules themselves fuse with the plasma membrane and release their entire contents extracellularly; piecemeal degranulation, whereby granule-derived cytokines are selectively mobilized into vesicles that emerge from granules, traverse the cytoplasm and fuse with the plasma membrane to release discrete packets of cytokines; and eosinophil cytolysis, whereby intact granules are extruded from eosinophils, and deposited within tissues. In this latter scenario, extracellular granules can themselves function as stimulus-responsive secretory-competent organelles within the tissue. Here, we review the distinctive processes of differential secretion of eosinophil granule-derived cytokines. PMID:25386174

  10. Eosinophilic enteritis: a rare cause of diarrhoea

    PubMed Central

    Llad, Ana; Oliveira, Jo緌; Silva, Pedro; Pinheiro, Sofia

    2013-01-01

    We report a case of a healthy young man presenting with 1-week history of diarrhoea, acute abdominal pain and weight loss. Laboratory investigation showed very high peripheral eosinophils levels. After exclusion of the other causes of eosinophilia, a histological bowel sample analysis revealed marked eosinophilic infiltration of a small bowel mucosal layer which confirmed the suspicion of eosinophilic enteritis. Unlike most of the described cases, this patient did not require any specific treatment. Eosinophilic gastroenteritis is a rare and heterogeneous disease that is probably underdiagnosed in clinical practice because it requires a high degree of suspicion and an endoscopic biopsy for definite diagnosis. PMID:24081600

  11. The Consequences of Not Having Eosinophils

    PubMed Central

    Gleich, G. J.; Klion, A. D.; Lee, J. J.; Weller, P. F.

    2014-01-01

    Several lines of evidence suggest that deficiency of eosinophils is not associated with any characteristic abnormality. Patients lacking eosinophils, in the setting of immunodeficiency or as a consequence of IgG-mediated eosinophil precursor destruction, do not display any distinguishing abnormalities related to eosinophil reduction. The observation that eosinophil-deficient mice do not display any distinctive syndrome or failure of their health is evidence that, under ordinary laboratory conditions, the eosinophil does not play a critical role in the well-being of mammals. Observations that monoclonal antibodies to interleukin-5 (IL-5) are well tolerated appear unsurprising in light of these findings. For example, patients with the hypereosinophilic syndrome have received mepolizumab, an anti-IL-5 monoclonal antibody, for as long as 6 years and have not developed any characteristic set of adverse events. Safety data for reslizumab, another anti-IL-5 monoclonal antibody, and benralizumab, a monoclonal antibody to the IL-5 receptor ?-chain, are comparatively limited, especially for benralizumab, although reports of administration of these antibodies to humans suggest that they are well tolerated. Thus, data to the present suggest that reduction of eosinophils appears to have no characteristic ill effects on normal health, and monoclonal antibodies that deplete eosinophils have the potential to be widely employed in the treatment of eosinophil-associated diseases. PMID:23742015

  12. Eosinophils: changing perspectives in health and disease

    PubMed Central

    Rosenberg, Helene F.; Dyer, Kimberly D.; Foster, Paul S.

    2015-01-01

    Eosinophils have been traditionally perceived as largely end-stage, cytotoxic effector cells. Recent studies have profoundly altered this simplistic view of eosinophils and their function. New insights into the molecular basis of development, trafficking and degranulation of eosinophils have provided a better understanding of the role of these cells in promoting homeostasis through their immunomodulatory functions. Likewise, recent developments have generated a more sophisticated view of how eosinophils contribute to the pathogenesis of disease, including asthma and primary hypereosinophilic syndromes, and also a more complete appreciation of their activities in parasitic infection. PMID:23154224

  13. Prevalence of oesophageal eosinophils and eosinophilic oesophagitis in adults: the population?based Kalixanda study

    PubMed Central

    Ronkainen, Jukka; Talley, Nicholas J; Aro, Pertti; Storskrubb, Tom; Johansson, Sven?Erik; Lind, Tore; Bolling?Sternevald, Elisabeth; Vieth, Michael; Stolte, Manfred; Walker, Marjorie M; Agr徼s, Lars

    2007-01-01

    Background Eosinophilic oesophagitis may be increasing but the prevalence in the general population remains unknown. Our aim was to assess this and the presence of eosinophils in the distal oesophageal epithelium in the community. Methods Oesophagogastroduodenoscopy was performed in a random sample (n?=?1000) of the adult Swedish population (mean age 54 years, 49% men). Oesophageal biopsy samples were obtained from 2?cm above, and at, the Z?line. Any eosinophil infiltration of the epithelium was defined as eosinophils present. Definite eosinophilic oesophagitis was defined as ?20, probable as 1519, and possible as 514 eosinophils/high?power field (HPF, at magnification 40) in oesophageal biopsy specimens. Results Eosinophils were present in 48 subjects (4.8%, 95% CI 3.5 to 6.1%, mean age 54 years, 63% men), in 54% without troublesome reflux symptoms. Definite eosinophilic oesophagitis was present in four subjects (0.4%, 95% CI 0.01 to 0.8%, mean age 51 years, 75% men) and probable eosinophilic oesophagitis in seven subjects (0.7%, 95% CI 0.2 to 1.2%, mean age 58 years, 43% men). Erosive oesophagitis (OR?=?2.99, 95% CI 1.58 to 5.66) and absence of dyspepsia (OR?=?0.23, 95% CI 0.07 to 0.75) and Helicobacter pylori infection (OR?=?0.41, 95% CI 0.19 to 0.92) were independent predictors for eosinophils present. Definite eosinophilic oesophagitis was associated with dysphagia (2/66 vs 2/926, p?=?0.025), and probable eosinophilic oesophagitis with narrowing of the oesophageal lumen (2/15 vs 5/978, p?=?0.005). Conclusions Oesophageal eosinophils were present in nearly 5% of the general population; approximately 1% had definite or probable eosinophilic oesophagitis. Oesophageal eosinophils may be a manifestation of reflux disease in adults, but the condition is as likely to be asymptomatic and go unrecognised. PMID:17135307

  14. Activation states of blood eosinophils in asthma

    PubMed Central

    Johansson, Mats W.

    2014-01-01

    Asthma is characterized by airway inflammation rich in eosinophils. Airway eosinophilia is associated with exacerbations and has been suggested to play a role in airway remodeling. Recruitment of eosinophils from the circulation requires that blood eosinophils become activated, leading to their arrest on the endothelium and extravasation. Circulating eosinophils can be envisioned as potentially being in different activation states, including non-activated, pre-activated or primed, or fully activated. In addition, the circulation can potentially be deficient of pre-activated or activated eosinophils, because such cells have marginated on activated endothelium or extravasated into the tissue. A number of eosinophil-surface proteins, including CD69, L-selectin, intercellular adhesion molecule-1 (ICAM-1, CD54), CD44, P-selectin glycoprotein ligand-1 (PSGL-1, CD162), cytokine receptors, Fc receptors, integrins including ?M integrin (CD11b), and activated conformations of Fc receptors and integrins have been proposed to report cell activation. Variation in eosinophil activation states may be associated with asthma activity. Eosinophil-surface proteins proposed to be activation markers, with a particular focus on integrins, and evidence for associations between activation states of blood eosinophils and features of asthma are reviewed here. Partial activation of ?1 and ?2 integrins on blood eosinophils, reported by monoclonal antibodies (mAb) N29 and KIM-127, is associated with impaired pulmonary function and airway eosinophilia, respectively, in non-severe asthma. The association with lung function does not occur in severe asthma, presumably due to greater eosinophil extravasation, specifically of activated or pre-activated cells, in severe disease. PMID:24552191

  15. Dietary treatment of eosinophilic esophagitis.

    PubMed

    Gonsalves, Nirmala; Kagalwalla, Amir F

    2014-06-01

    Emerging evidence supports impaired epithelial barrier function as the key initial event in the development of eosinophilic esophagitis (EoE) and other allergic diseases. Symptom resolution, histologic remission, and prevention of both disease and treatment-related complications are the goals of treatment. Successful dietary treatments include elemental, empirical elimination and allergy test directed diets. Dietary therapy with exclusive elemental diet offers the best response. Cow's milk, wheat, egg, soy, peanut/tree nut, and fish/shellfish are the 6 food antigens most likely to induce esophageal inflammation. PMID:24813522

  16. Pneumothorax in pulmonary eosinophilic granuloma

    PubMed Central

    Gelfand, Elliot T.; Sheiner, Nathan M.

    1974-01-01

    The cases are described of two patients with pulmonary eosinophilic granuloma who presented with spontaneous pneumothorax. Prolonged air leak and recurrence of the pneumothorax after initial re-expansion of the lung occurred in both patients. In one of the patients the pneumothorax was simultaneously bilateral and almost complete. Thoracotomy, with aggressive and total pleurodesis, is recommended in the management of these patients to prevent recurrence and complications. Lung biopsy should be performed in all patients undergoing thoracotomy for recurrent pneumothorax. ImagesFIG. 1FIG. 2FIG. 3FIG. 4 PMID:4824967

  17. Roles of integrin activation in eosinophil function and the eosinophilic inflammation of asthma.

    PubMed

    Barthel, Steven R; Johansson, Mats W; McNamee, Dawn M; Mosher, Deane F

    2008-01-01

    Eosinophilic inflammation is a characteristic feature of asthma. Integrins are highly versatile cellular receptors that regulate extravasation of eosinophils from the postcapillary segment of the bronchial circulation to the airway wall and airspace. Such movement into the asthmatic lung is described as a sequential, multistep paradigm, whereby integrins on circulating eosinophils become activated, eosinophils tether in flow and roll on bronchial endothelial cells, integrins on rolling eosinophils become further activated as a result of exposure to cytokines, eosinophils arrest firmly to adhesive ligands on activated endothelium, and eosinophils transmigrate to the airway in response to chemoattractants. Eosinophils express seven integrin heterodimeric adhesion molecules: alpha 4 beta 1 (CD49d/29), alpha 6 beta 1 (CD49f/29), alpha M beta 2 (CD11b/18), alpha L beta 2 (CD11a/18), alpha X beta 2 (CD11c/18), alpha D beta2 (CD11d/18), and alpha 4 beta 7 (CD49d/beta 7). The role of these integrins in eosinophil recruitment has been elucidated by major advances in the understanding of integrin structure, integrin function, and modulators of integrins. Such findings have been facilitated by cellular experiments of eosinophils in vitro, studies of allergic asthma in humans and animal models in vivo, and crystal structures of integrins. Here, we elaborate on how integrins cooperate to mediate eosinophil movement to the asthmatic airway. Antagonists that target integrins represent potentially promising therapies in the treatment of asthma. PMID:17906117

  18. Pattern-recognition receptors in human eosinophils.

    PubMed

    Kvarnhammar, Anne M幩sson; Cardell, Lars Olaf

    2012-05-01

    The pattern-recognition receptor (PRR) family includes Toll-like receptors (TLRs), nucleotide-binding oligomerization domain (NOD) -like receptors (NLRs), RIG-I-like receptors (RLRs), C-type lectin receptors (CLRs) and the receptor for advanced glycation end products (RAGE). They recognize various microbial signatures or host-derived danger signals and trigger an immune response. Eosinophils are multifunctional leucocytes involved in the pathogenesis of several inflammatory processes, including parasitic helminth infection, allergic diseases, tissue injury and tumour immunity. Human eosinophils express several PRRs, including TLR1-5, TLR7, TLR9, NOD1, NOD2, Dectin-1 and RAGE. Receptor stimulation induces survival, oxidative burst, activation of the adhesion system and release of cytokines (interleukin-1?, interleukin-6, tumour necrosis factor-? and granulocyte-macrophage colony-stimulating factor), chemokines (interleukin-8 and growth-related oncogene-?) and cytotoxic granule proteins (eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase and major basic protein). It is also evident that eosinophils play an immunomodulatory role by interacting with surrounding cells. The presence of a broad range of PRRs in eosinophils indicates that they are not only involved in defence against parasitic helminths, but also against bacteria, viruses and fungi. From a clinical perspective, eosinophilic PRRs seem to be involved in both allergic and malignant diseases by causing exacerbations and affecting tumour growth, respectively. PMID:22242941

  19. Gallium-67 pulmonary uptake in eosinophilic pneumonia

    SciTech Connect

    Morais, J.; Carrier, L.; Gariepy, G.; Le Bel, L.; Chartrand, R.; Picard, D.

    1988-01-01

    Eosinophilic pneumonia is usually diagnosed based on the findings on chest x-ray, white blood count, and transbronchial biopsy. After reporting a case of Ga-67 lung uptake in eosinophilic pneumonia, its histopathology is discussed and the mechanisms of Ga-67 uptake by inflammatory lesions are reviewed.

  20. Eosinophilic Gastroenteritis and Colitis: a Comprehensive Review.

    PubMed

    Uppal, Vikas; Kreiger, Portia; Kutsch, Erika

    2016-04-01

    Eosinophilic gastrointestinal disorders, including eosinophilic esophagitis, gastroenteritis, and colitis, refer to a spectrum of clinical diseases that present with variable degrees of infiltration of the gastrointestinal tract by eosinophils in the absence of other known causes of tissue eosinophilia. Clinical symptoms and laboratory findings are usually non-specific and may or may not be accompanied by peripheral blood eosinophilia. The extent of eosinophilic infiltration of the gastrointestinal wall varies from mucosal to transmural and serosal involvement. Diagnosis requires presence of gastrointestinal symptoms, demonstration of gastrointestinal eosinophilia by biopsy, and exclusion of other known causes of tissue eosinophilia. Many studies have pointed toward the eosinophil as the major offender; however, the exact functional role of the eosinophil in the pathogenesis of eosinophilic gastrointestinal disorders remains unclear. The roles of T-helper-2 cytokines and other mediators, such as eotaxin-1 and interleukin-5, have gained significant importance in the pathobiology of eosinophilic gastrointestinal disorders. Current understanding of treatment is based on case reports and a few case series, as there is a lack of large prospective studies. Steroids are currently the mainstay of therapy, but the roles of other drugs such as leukotriene inhibitors, mast cell stabilizers, interleukin-5 inhibitors, and anti-immunoglobulin E, along with other targets in the immune pathway, are currently being explored. PMID:26054822

  1. Eosinophils in hereditary and inflammatory myopathies.

    PubMed

    Schr繹der, Thomas; Fuchss, Johann; Schneider, Ilka; Stoltenburg-Didinger, Gisela; Hanisch, Frank

    2013-12-01

    It is not known whether eosinophilic myositis is a specific histopathological feature of limb girdle muscular dystrophy 2A (LGMD2A). Number and location of eosinophils in skeletal muscle biopsies (n=100) was analysed by Giemsa and modified hematoxylin/eosin staining in patients with genetically confirmed myopathies (LGMD2A, LGMD2B, LGMD2L, facioscapulohumeral muscular dystrophy, dystrophinopathy), histologically confirmed idiopathic inflammatory myopathies (sporadic inclusion body myositis (sIBM), dermatomyositis (DM), polymyositis), amyotrophic lateral sclerosis (neurogenic control), and normal controls. The number of eosinophils/mm簡 was significantly higher in LGMD2A, PM, DM, and sIBM compared to controls but not significantly higher than other myopathies. A large overlap in the number of eosinophils/mm2 between all groups was seen. In all disease groups eosinophils were mainly found endomysially (46- 88%) and intra- and perivascularly (4-37%). There was no correlation between the numbers of eosinophils/mm簡 and (i) age at biopsy and (ii) the duration of the disease. The extent of myopathic, fibrotic, and inflammatory changes did not differ in samples with high and low eosinophil count. Eosinophils seem to represent an unspecific histological finding in hereditary and inflammatory myopathies, but also amyotrophic lateral sclerosis. PMID:24803842

  2. 帣-lactam-associated eosinophilic colitis.

    PubMed

    Mogilevski, Tamara; Nickless, David; Hume, Sam

    2015-01-01

    A 42-year-old man with a history of childhood asthma presented with a 2-week history of watery diarrhoea and marked peripheral eosinophilia in the setting of recent use of cephalexin. His colonoscopy revealed patchy colitis. Biopsies were consistent with eosinophilic colitis. Two months later he received a course of amoxicillin resulting in recurrence of peripheral eosinophilia. Given the time-frame of 帣-lactam administration to symptom onset and elimination of all other precipitating causes, he was diagnosed with 帣-lactam-associated eosinophilic colitis. The patient's symptoms resolved and peripheral eosinophil count decreased with no specific treatment. Eosinophilic colitis is a rare heterogeneous condition, the pathogenesis of which is likely to be an interplay between environmental and genetic factors. It can be secondary to a helminthic infection or a drug reaction and has been associated with ulcerative colitis. If secondary causes of eosinophilic colitis have been excluded, the mainstay of treatment is with corticosteroids. PMID:26106168

  3. Eosinophils in innate immunity: an evolving story

    PubMed Central

    Shamri, Revital; Xenakis, Jason J.; Spencer, Lisa A.

    2013-01-01

    Eosinophils are innate immune leukocytes found in relatively low numbers within the blood. Terminal effector functions of eosinophils, deriving from their capacity to release their content of tissue-destructive cationic proteins, have historically been considered primary effector mechanisms against specific parasites, and are likewise implicated in tissue damage accompanying allergic responses such as asthma. However, the past decade has seen dramatic advancements in the field of eosinophil immunobiology, revealing eosinophils to also be key participants in many other facets of innate immunity, from bridging innate and adaptive immune responses to orchestrating tissue remodeling events. Here, we review the multifaceted functions of eosinophils in innate immunity that are currently known, and discuss new avenues in this evolving story. PMID:21042920

  4. The pathophysiology of eosinophilic esophagitis.

    PubMed

    Raheem, Mayumi; Leach, Steven T; Day, Andrew S; Lemberg, Daniel A

    2014-01-01

    Eosinophilic esophagitis (EoE) is an emerging disease characterized by esophageal eosinophilia (>15eos/hpf), lack of responsiveness to acid-suppressive medication and is managed by allergen elimination and anti-allergy therapy. Although the pathophysiology of EoE is currently unsubstantiated, evidence implicates food and aeroallergen hypersensitivity in genetically predisposed individuals as contributory factors. Genome-wide expression analyses have isolated a remarkably conserved gene-expression profile irrespective of age and gender, suggesting a genetic contribution. EoE has characteristics of mainly TH2 type immune responses but also some TH1 cytokines, which appear to strongly contribute to tissue fibrosis, with esophageal epithelial cells providing a hospitable environment for this inflammatory process. Eosinophil-degranulation products appear to play a central role in tissue remodeling in EoE. This remodeling and dysregulation predisposes to fibrosis. Mast-cell-derived molecules such as histamine may have an effect on enteric nerves and may also act in concert with transforming growth factor-? to interfere with esophageal musculature. Additionally, the esophageal epithelium may facilitate the inflammatory process under pathogenic contexts such as in EoE. This article aims to discuss the contributory factors in the pathophysiology of EoE. PMID:24910846

  5. Coccidioidomycosis Masquerading as Eosinophilic Ascites

    PubMed Central

    Alavi, Kourosh; Atla, Pradeep R.; Haq, Tahmina; Sheikh, Muhammad Y.

    2015-01-01

    Endemic to the southwestern parts of the United States, coccidioidomycosis, also known as Valley Fever, is a common fungal infection that primarily affects the lungs in both acute and chronic forms. Disseminated coccidioidomycosis is the most severe but very uncommon and usually occurs in immunocompromised individuals. It can affect the central nervous system, bones, joints, skin, and, very rarely, the abdomen. This is the first case report of a patient with coccidioidal dissemination to the peritoneum presenting as eosinophilic ascites (EA). A 27-year-old male presented with acute abdominal pain and distention from ascites. He had eosinophilia of 11.1% with negative testing for stool studies, HIV, and tuberculosis infection. Ascitic fluid exam was remarkable for low serum-ascites albumin gradient (SAAG), PMN count >250/mm3, and eosinophils of 62%. Abdominal imaging showed thickened small bowel and endoscopic testing negative for gastric and small bowel biopsies. He was treated empirically for spontaneous bacterial peritonitis, but no definitive diagnosis could be made until coccidioidal serology returned positive. We noted complete resolution of symptoms with oral fluconazole during outpatient follow-up. Disseminated coccidioidomycosis can present in an atypical fashion and may manifest as peritonitis with low SAAG EA. The finding of EA in an endemic area should raise the suspicion of coccidioidal dissemination. PMID:26266062

  6. 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. ...

  7. Eosinophil adoptive transfer system to directly evaluate pulmonary eosinophil trafficking in vivo

    PubMed Central

    Wen, Ting; Besse, John A.; Mingler, Melissa K.; Fulkerson, Patricia C.; Rothenberg, Marc E.

    2013-01-01

    Most in vivo studies of granulocytes draw conclusions about their trafficking based on examination of their steady-state tissue/blood levels, which result from a combination of tissue homing, survival, and egress, rather than direct examination of cellular trafficking. Herein, we developed a unique cell transfer system involving the adoptive transfer of a genetically labeled, bone-marrowderived unique granulocyte population (eosinophils) into an elicited inflammatory site, the allergic lung. A dual polychromatic FACS-based biomarker-labeling system based on the IL4-eGFP transgene (4get) or Cd45.1 allele was used to track i.v. transferred eosinophils into the airway following allergen or TH2-associated stimuli in the lung in multiple mouse strains. The system was amenable to reverse tagging of recipients, thus allowing transfer of nonlabeled eosinophils and competitive tracking of multiple populations of eosinophils in vivo. The half-life of eosinophils in the blood was 3 h, and migration to the lung was dependent upon the dosage of transferred eosinophils, sensitive to pertussis toxin pretreatment, peaked at ?24 h after adoptive transfer, and revealed a greater than 8-d eosinophil half-life in the lung. Eosinophil migration to the lung was dependent upon recipient IL-5 and IL-13 receptor ?1 and donor eosinophil C-C chemokine receptor type 3 (CCR3) and interleukin 1 receptor-like 1 (ST2) in vivo. Taken together, this unique eosinophil transfer system provides an unprecedented opportunity to examine airway eosinophil migration without the need for extensive efforts to acquire donor source and time-consuming genetic crossing and has already been used to identify a long eosinophil half-life in the allergic lung and a definite role for ST2 in regulating eosinophil trafficking. PMID:23536294

  8. Eosinophil adoptive transfer system to directly evaluate pulmonary eosinophil trafficking in vivo.

    PubMed

    Wen, Ting; Besse, John A; Mingler, Melissa K; Fulkerson, Patricia C; Rothenberg, Marc E

    2013-04-01

    Most in vivo studies of granulocytes draw conclusions about their trafficking based on examination of their steady-state tissue/blood levels, which result from a combination of tissue homing, survival, and egress, rather than direct examination of cellular trafficking. Herein, we developed a unique cell transfer system involving the adoptive transfer of a genetically labeled, bone-marrow-derived unique granulocyte population (eosinophils) into an elicited inflammatory site, the allergic lung. A dual polychromatic FACS-based biomarker-labeling system based on the IL4-eGFP transgene (4get) or Cd45.1 allele was used to track i.v. transferred eosinophils into the airway following allergen or T(H)2-associated stimuli in the lung in multiple mouse strains. The system was amenable to reverse tagging of recipients, thus allowing transfer of nonlabeled eosinophils and competitive tracking of multiple populations of eosinophils in vivo. The half-life of eosinophils in the blood was 3 h, and migration to the lung was dependent upon the dosage of transferred eosinophils, sensitive to pertussis toxin pretreatment, peaked at ?24 h after adoptive transfer, and revealed a greater than 8-d eosinophil half-life in the lung. Eosinophil migration to the lung was dependent upon recipient IL-5 and IL-13 receptor ?1 and donor eosinophil C-C chemokine receptor type 3 (CCR3) and interleukin 1 receptor-like 1 (ST2) in vivo. Taken together, this unique eosinophil transfer system provides an unprecedented opportunity to examine airway eosinophil migration without the need for extensive efforts to acquire donor source and time-consuming genetic crossing and has already been used to identify a long eosinophil half-life in the allergic lung and a definite role for ST2 in regulating eosinophil trafficking. PMID:23536294

  9. Tyrosine Kinase Inhibitors and Therapeutic Antibodies in Advanced Eosinophilic Disorders and Systemic Mastocytosis.

    PubMed

    Gotlib, Jason

    2015-12-01

    World Health Organization-defined myeloproliferative neoplasms share a common pathobiologic theme of constitutive activation of tyrosine kinases (TKs). While myeloid/lymphoid neoplasms with eosinophilia and rearrangement of PDGFRA or PDGFRB exhibit exquisite responsiveness to imatinib, other eosinophilic disorders such as chronic eosinophilic leukemia-not otherwise specified (CEL-NOS) and idiopathic hypereosinophilic syndrome (HES) lack recurrent gene mutations or known druggable targets. In systemic mastocytosis (SM), KIT D816V is identified in 90% of patients, but demonstrates imatinib resistance. Recently, the multikinase/KIT inhibitor midostaurin (PKC412) has demonstrated encouraging activity in patients with advanced SM, and selective KIT D816V inhibitors are entering clinical development. Pre-clinical rationale also exists for use of small molecule inhibitors of TK-linked pathways (e.g., BTK, JAK-STAT, PI3K/AKT, and FGFR1) that are implicated in normal or dysregulated signaling in eosinophils or mast cells. A complementary therapeutic approach is the use of naked antibody (e.g., mepolizumab and alemtuzumab) or antibody-based drug immunoconjugates (brentuximab vedotin) against targets expressed on the surface of eosinophils or mastocytes that can block proliferation and/or induce apoptosis of these cells. Ultimately, biologic and molecular characterization of eosinophilia and SM cases will help to optimize selection of TK inhibitors or therapeutic antibodies for individual patients. PMID:26404639

  10. Severe Aplastic Anemia Associated With Eosinophilic Fasciitis

    PubMed Central

    de Masson, Ad鋩e; de Latour, R嶲is Peffault; Benhamou, Ygal; Molu蔞n-Chabrot, C嶰ile; Bay, Jacques-Olivier; Laquerri鋨e, Annie; Picquenot, Jean-Michel; Michonneau, David; Leguy-Seguin, Vanessa; Rybojad, Michel; Bonnotte, Bernard; Jardin, Fabrice; L憝esque, Herv; Bagot, Martine; Soci, G廨ard

    2013-01-01

    Abstract Diffuse eosinophilic fasciitis (Shulman disease) is a rare sclerodermiform syndrome that, in most cases, resolves spontaneously or after corticosteroid therapy. It has been associated with hematologic disorders, such as aplastic anemia. The clinical features and long-term outcomes of patients with eosinophilic fasciitis and associated aplastic anemia have been poorly described. We report the cases of 4 patients with eosinophilic fasciitis and associated severe aplastic anemia. For 3 of these patients, aplastic anemia was refractory to conventional immunosuppressive therapy with antithymocyte globulin and cyclosporine. One of the patients received rituximab as a second-line therapy with significant efficacy for both the skin and hematologic symptoms. To our knowledge, this report is the first to describe rituximab used to treat eosinophilic fasciitis with associated aplastic anemia. In a literature review, we identified 19 additional cases of eosinophilic fasciitis and aplastic anemia. Compared to patients with isolated eosinophilic fasciitis, patients with eosinophilic fasciitis and associated aplastic anemia were more likely to be men (70%) and older (mean age, 56 yr; range, 1871 yr). Corticosteroid-containing regimens improved skin symptoms in 5 (42%) of 12 cases but were ineffective in the treatment of associated aplastic anemia in all but 1 case. Aplastic anemia was profound in 13 cases (57%) and was the cause of death in 8 cases (35%). Only 5 patients (22%) achieved long-term remission (allogeneic hematopoietic stem cell transplantation: n = 2; cyclosporine-containing regimen: n = 2; high-dose corticosteroid-based regimen: n = 1). PMID:23429351

  11. Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML)

    ClinicalTrials.gov

    2013-01-22

    Leukemia, Lymphocytic, Acute; Leukemia; Leukemia Acute Promyelocytic Leukemia (APL); Leukemia Acute Lymphoid Leukemia (ALL); Leukemia Chronic Myelogenous Leukemia (CML); Leukemia Acute Myeloid Leukemia (AML); Leukemia Chronic Lymphocytic Leukemia (CLL)

  12. Eosinophilic gastroenteritis presenting in an adolescent with isolated colonic involvement.

    PubMed Central

    Moore, D; Lichtman, S; Lentz, J; Stringer, D; Sherman, P

    1986-01-01

    Eosinophilic gastroenteritis most commonly involves the stomach and proximal small intestine with eosinophilic inflammation of either the mucosa, submucosa or serosa. The patient reported here had isolated eosinophilic colitis. The initial presentation with iron deficiency anaemia owing to occult gastrointestinal blood loss emphasises the need to evaluate the entire gastrointestinal tract in patients with eosinophilic gastroenteritis. Images Fig. 1 Fig. 2 PMID:3781337

  13. Use of AN Eosinophil Specific Monoclonal Antibody in Assessing Eosinophil Function.

    NASA Astrophysics Data System (ADS)

    Minkoff, Marjorie Sue

    A monoclonal antibody to an eosinophil specific determinant is very important in assessing eosinophil function during helminthic infection. Eosinophils induced by Schistosoma mansoni infection in BALB/c mice were used to induce C57B1/6 immunocytes for production of hybridomas secreting eosinophil monoclonal antibodies. These antibodies were shown to react with an eosinophil surface epitope but not with neutrophils or macrophages as determined by ELISA, immunodiffusion, immunofluorescence, and immunoblot assay. Affinity chromatography with eosinophil chemotactic factor-sepharose consistently selected out a { rm M_ R} 67,000 protein from solubilized eosinophil membrane antigens but not from neutrophil and macrophage antigens. In vitro studies showed that the eosinophil-specific monoclonal antibodies abrogated antibody-dependent eosinophil -mediated killing of S. mansoni schistosomula using mouse, rat or human eosinophils. Neutrophil and macrophage killing activities were unaffected. The monoclonal antibodies effected complement-dependent lysis of mouse and rat eosinophils but not of human eosinophils. ECF-treated eosinophils showed enhanced killing of schistosomula which was blocked by the monoclonal antibody. Murine and human eosinophils preincubated with monoclonal antibody exhibited decreased chemotaxis to ECF at optimal chemotactic concentrations. The monoclonal antibody also blocked eosinophil binding to ECF- sepharose beads. In vivo induction of peripheral blood eosinophilia by injection of S. mansoni eggs was suppressed by injections of monoclonal antibodies 2CD13 and 2QD45 in mouse and rat experimental models. Eosinophilia induced by keyhole limpet hemocyanin- cyclophosphamide treatment was also suppressed by monoclonal antibody in both murine and rat systems. Pulmonary granulomas in mice given egg injection and monoclonal antibody were smaller and contained fewer eosinophils than those granulomas from mice given eggs only. In immuno-biochemical studies, the monoclonal antibody 2QD45 specifically immunoprecipitated the {rm M_ R} 67,000 ECF-binding protein from ^{125}{rm I}-labeled mouse, rat, and human eosinophils as assessed by SDS-PAGE and autoradiography. Two-dimensional gel electrophoresis showed that this ECF-binding protein has a lower PI point than either mouse or bovine albumin.

  14. Esophageal Microbiome in Eosinophilic Esophagitis

    PubMed Central

    Harris, J. Kirk; Fang, Rui; Wagner, Brandie D.; Choe, Ha Na; Kelly, Caleb J.; Schroeder, Shauna; Moore, Wendy; Stevens, Mark J.; Yeckes, Alyson; Amsden, Katie; Kagalwalla, Amir F.; Zalewski, Angelika; Hirano, Ikuo; Gonsalves, Nirmala; Henry, Lauren N.; Masterson, Joanne C.; Robertson, Charles E.; Leung, Donald Y.; Pace, Norman R.; Ackerman, Steven J.; Furuta, Glenn T.; Fillon, Sophie A.

    2015-01-01

    Objective The microbiome has been implicated in the pathogenesis of a number of allergic and inflammatory diseases. The mucosa affected by eosinophilic esophagitis (EoE) is composed of a stratified squamous epithelia and contains intraepithelial eosinophils. To date, no studies have identified the esophageal microbiome in patients with EoE or the impact of treatment on these organisms. The aim of this study was to identify the esophageal microbiome in EoE and determine whether treatments change this profile. We hypothesized that clinically relevant alterations in bacterial populations are present in different forms of esophagitis. Design In this prospective study, secretions from the esophageal mucosa were collected from children and adults with EoE, Gastroesophageal Reflux Disease (GERD) and normal mucosa using the Esophageal String Test (EST). Bacterial load was determined using quantitative PCR. Bacterial communities, determined by 16S rRNA gene amplification and 454 pyrosequencing, were compared between health and disease. Results Samples from a total of 70 children and adult subjects were examined. Bacterial load was increased in both EoE and GERD relative to normal subjects. In subjects with EoE, load was increased regardless of treatment status or degree of mucosal eosinophilia compared with normal. Haemophilus was significantly increased in untreated EoE subjects as compared with normal subjects. Streptococcus was decreased in GERD subjects on proton pump inhibition as compared with normal subjects. Conclusions Diseases associated with mucosal eosinophilia are characterized by a different microbiome from that found in the normal mucosa. Microbiota may contribute to esophageal inflammation in EoE and GERD. PMID:26020633

  15. Novel targeted therapies for eosinophilic disorders

    PubMed Central

    Wechsler, Michael E.; Fulkerson, Patricia C.; Bochner, Bruce S.; Gauvreau, Gail M.; Gleich, Gerald J.; Henkel, Tim; Kolbeck, Roland; Mathur, Sameer K.; Ortega, Hector; Patel, Jatin; Prussin, Calman; Renzi, Paolo; Rothenberg, Marc E.; Roufosse, Florence; Simon, Dagmar; Simon, Hans-Uwe; Wardlaw, Andrew; Weller, Peter F.; Klion, Amy D.

    2013-01-01

    Hypereosinophilic syndromes (HESs) are a diverse group of conditions characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. HESs are chronic disorders with significant morbidity and mortality. Although the availability of targeted chemotherapeutic agents, including imatinib, has improved quality of life and survival in some patients with HESs, additional agents with increased efficacy and decreased toxicity are sorely needed. The purpose of this review is to provide an overview of eosinophil biology with an emphasis on potential targets of pharmacotherapy and to provide a summary of potential eosinophil-targeting agents, including those in development, in clinical trials, or approved for other disorders. PMID:22935585

  16. Idiopathic eosinophilic meningoencephalomyelitis in a Rottweiler dog.

    PubMed

    Olivier, Alicia K; Parkes, Jennifer D; Flaherty, Heather A; Kline, Karen L; Haynes, Joseph S

    2010-07-01

    A 6-month-old, female, intact Rottweiler dog was presented to the Iowa State University Veterinary Teaching Hospital for a progressive history of abnormal behavior and generalized ataxia. At necropsy, there was eosinophilic infiltration of the brain and spinal cord, most severe in the medulla oblongata, cerebellum, and cervical spinal cord. Infiltrates of eosinophils were also present in the liver and small intestines. The dog was diagnosed with idiopathic eosinophilic meningoencephalomyelitis based on cerebrospinal fluid analysis, histopathology, and special stains to exclude etiologic agents. PMID:20622243

  17. Eosinophilic follicular reaction induced by Demodex folliculorum mite: a different disease from eosinophilic folliculitis.

    PubMed

    Sabater-Marco, V; Escutia-Mu隳z, B; Botella-Estrada, R

    2015-06-01

    Eosinophilic folliculitis (EF) is an idiopathic dermatitis included in the spectrum of eosinophilic pustular follicular reactions. Demodex folliculorum has been implicated as contributing to the pathogenesis of human immunodeficiency virus-associated EF, but it has not been described outside this context. We present an immunocompetent 65-year-old white man with a 5-year history of recurrent pruritic erythematous and oedematous lesions on his face, neck and scalp. Histopathologically, an eosinophilic microabcess with Demodex folliculorum mite within a pilosebaceous follicle was seen, and considered the causal agent. There were also accumulations of eosinophil granules on collagen bundles, and flame figure formations in the dermis. We believe that 'eosinophilic follicular reaction' is an appropriate term to describe this case of EF induced by D. folliculorum and thus distinguish it from the idiopathic form of EF. Moreover, this case suggests that D. folliculorum can sometimes induce an eosinophilic immune reaction. PMID:25623943

  18. Developmental, Malignancy-Related, and Cross-Species Analysis of Eosinophil, Mast Cell, and Basophil Siglec-8 Expression

    PubMed Central

    Hudson, Sherry A.; Herrmann, Harald; Du, Jian; Cox, Paul; Haddad, El-Bdaoui; Butler, Barbara; Crocker, Paul R.; Ackerman, Steven J.; Valent, Peter

    2012-01-01

    Objective The aim of this study is to determine when during hematopoiesis Siglec-8 gets expressed, whether it is expressed on hematologic malignancies, and if there are other non-human species that express Siglec-8. Methods Siglec-8 mRNA and cell surface expression was monitored during in vitro maturation of human eosinophils and mast cells. Flow cytometry was performed on human blood and bone marrow samples, and on blood samples from dogs, baboons, and rhesus and cynomolgus monkeys. Results Siglec-8 is a late maturation marker. It is detectable on eosinophils and basophils from subjects with chronic eosinophilic leukemia, chronic myelogenous leukemia, and on malignant and non-malignant bone marrow mast cells, as well as the HMC-1.2 cell line. None of the Siglec-8 monoclonal antibodies tested recognized leukocytes from dogs, baboons, and rhesus and cynomolgus monkeys. Conclusions Siglec-8-based therapies should not target immature human leukocytes but should recognize mature and malignant eosinophils, mast cells, and basophils. So far, there is no suitable species for preclinical testing of Siglec-8 monoclonal antibodies. PMID:21938510

  19. Migratory eosinophilic alveolitis caused by radiation therapy.

    PubMed

    Lim, Jun Hyeok; Nam, Hae-Seong; Kim, Hun Jung; Choi, Chang-Hwan; Park, In-Suh; Cho, Jae Hwa; Ryu, Jeong-Seon; Kwak, Seung Min; Lee, Hong Lyeol

    2015-05-01

    Although radiation pneumonitis is usually confined to irradiated areas, some studies have reported that radiation-induced lymphocytic alveolitis can also spread to the non-irradiated lung. However, there have been few reports of radiation-induced eosinophilic alveolitis. We report the case of a 27-year-old female with radiation pneumonitis, occurring 4 months after radiation therapy for cancer of the left breast. Clinical and radiological relapse followed withdrawal of corticosteroids. Examination of bronchoalveolar lavage (BAL) in patchy airspace consolidations revealed increased eosinophil counts. Finally, clinical and radiological signs resolved rapidly after reintroduction of corticosteroids. Eosinophilic alveolitis may be promoted by radiation therapy. In the present case report, possible mechanisms for radiation-induced eosinophilic alveolitis are also reviewed. PMID:26101656

  20. Spectrum of Surgical Presentation of Eosinophilic Enteritis

    PubMed Central

    Shetty, Spoorthy Sudhakar; Shetty, Charan Kishor

    2015-01-01

    Eosinophilic enteritis is a rare disorder presenting mostly with diarrhea, malabsorption, abdominal pain, weight loss, and hypersensitivity. Surgical manifestation of eosinophilic gastrointestinal disorders depends on the site and extent of involvement. In our case series of four patients two of them had ileocaecal masses with recurrent subacute intestinal obstruction with past history of intake of antitubercular drugs for 9 months. On histopathological examination both of them proved to have eosinophilic enterocolitis. Thus it is a clinical dilemma to differentiate between these two conditions. The other two patients presented as acute abdomen with perforation and intussusception. All four patients were treated surgically. Postoperatively they recovered well with no symptoms on one year follow-up. In Indian setup tuberculosis being rampant there may be under reporting or wrongly diagnosed cases of eosinophilic enteritis. Thus a strong clinical suspicion and awareness of this clinical entity are essential among surgical community. PMID:25960910

  1. Imipenem/cilastatin-induced acute eosinophilic pneumonia.

    PubMed

    Foong, Kap Sum; Lee, Ashley; Pekez, Marijeta; Bin, Wei

    2016-01-01

    Drugs, toxins, and infections are known to cause acute eosinophilic pneumonia. Daptomycin and minocycline are the commonly reported antibiotics associated with acute eosinophilic pneumonia. In this study, we present a case of imipenem/cilastatin-induced acute eosinophilic pneumonia. The patient presented with fever, acute hypoxic respiratory distress, and diffuse ground-glass opacities on the chest CT a day after the initiation of imipenem/cilastatin. Patient also developed peripheral eosinophilia. A reinstitution of imipenem/cilastatin resulted in recurrence of the signs and symptoms. A bronchoscopy with bronchoalveolar lavage showed 780 nucleated cells/mm(3) with 15% eosinophil. The patient's clinical condition improved significantly after the discontinuation of imipenem/cilastatin therapy and the treatment with corticosteroid. PMID:26944380

  2. Genetics Home Reference: Eosinophil peroxidase deficiency

    MedlinePLUS

    ... following resources about eosinophil peroxidase deficiency helpful. These materials are written for the general public. MedlinePlus - Health information Educational resources - Information pages (2 links) Patient support - For patients and families (3 links) You may also be interested in ...

  3. What Is Childhood Leukemia?

    MedlinePLUS

    ... be divided into 2 types. Chronic myelogenous leukemia (CML): This leukemia rarely occurs in children. Treatment is ... chronic myelogenous leukemia ). For more detailed information on CML, see Leukemia--Chronic Myeloid . Chronic lymphocytic leukemia (CLL): ...

  4. Eosinophilic diseases of the gastrointestinal tract.

    PubMed

    Lucendo, Alfredo J

    2010-09-01

    Eosinophilic gastrointestinal disorders (EGIDs) are a diverse group of disorders whose diagnosis is on the rise and are characterized by symptoms caused by infiltration by eosinophils of the different sections of the digestive tract. Although little is known of their etiology, it seems to be multifactorial. Alteration of the immunological capacity of the digestive mucosa is determined by the exposure of genetically predisposed individuals to potential airborne or food allergens. EGIDs are classified based on the location of the inflammatory response even though their symptoms, prognosis, and treatment vary considerably. Eosinophilic esophagitis is the most widely recognized entity in this family and is characterized by exclusive eosinophilic infiltration of the esophagus. Breakthroughs in understanding its etiopathogeny have been extrapolated to eosinophilic gastroenteritis, a rare disease identified many years ago commonly involving the stomach and small bowel which should be distinguished from hypereosinophilic syndrome. Eosinophilic colitis, which usually affects children, could be considered a specific non-IgE-mediated allergy to food protein. The physiopathological bases of these entities need to be established in order to define specific treatment aimed at preventing and altering their clinical evolution. PMID:20509820

  5. Protein Radical Formation Resulting from Eosinophil Peroxidase-catalyzed Oxidation of Sulfite.

    PubMed

    Ranguelova, Kalina; Chatterjee, Saurabh; Ehrenshaft, Marilyn; Ramirez, Dario C; Summers, Fiona A; Kadiiska, Maria B; Mason, Ronald P

    2010-07-30

    Eosinophil peroxidase (EPO) is an abundant heme protein in eosinophils that catalyzes the formation of cytotoxic oxidants implicated in asthma, allergic inflammatory disorders, and cancer. It is known that some proteins with peroxidase activity (horseradish peroxidase and prostaglandin hydroperoxidase) can catalyze oxidation of bisulfite (hydrated sulfur dioxide), leading to the formation of sulfur trioxide anion radical ((.)SO(3)(-)). This free radical further reacts with oxygen to form peroxymonosulfate anion radical ((-)O(3)SOO(.)) and the very reactive sulfate anion radical (SO(4)()), which is nearly as strong an oxidant as the hydroxyl radical. However, the ability of EPO to generate reactive sulfur radicals has not yet been reported. Here we demonstrate that eosinophil peroxidase/H(2)O(2) is able to oxidize bisulfite, ultimately forming the sulfate anion radical (SO(4)()), and that these reactive intermediates can oxidize target proteins to protein radicals, thereby initiating protein oxidation. We used immuno-spin trapping and confocal microscopy to study protein oxidation by EPO/H(2)O(2) in the presence of bisulfite in a pure enzymatic system and in human promyelocytic leukemia HL-60 clone 15 cells, maturated to eosinophils. Polyclonal antiserum raised against the spin trap 5,5-dimethyl-1-pyrroline N-oxide (DMPO) detected the presence of DMPO covalently attached to the proteins resulting from the DMPO trapping of protein free radicals. We found that sulfite oxidation mediated by EPO/H(2)O(2) induced the formation of radical-derived DMPO spin-trapped human serum albumin and, to a lesser extent, of DMPO-EPO. These studies suggest that EPO-dependent oxidative damage may play a role in tissue injury in bisulfite-exacerbated eosinophilic inflammatory disorders. PMID:20501663

  6. Allergic mechanisms of Eosinophilic oesophagitis.

    PubMed

    Leung, John; Beukema, Koen Robert; Shen, Alice Hangzhou

    2015-10-01

    Eosinophilic oesophagitis (EoE) is characterized by oesophageal dysfunction and oesophageal eosinophilia refractory to proton-pump-inhibitor treatment. EoE is a food allergy, as elimination of food trigger(s) abrogates the disease, while trigger reintroduction causes recurrence. The allergic mechanism of EoE involves both IgE and non-IgE processes. There is a break in oral tolerance, the immune mechanism allowing enteric exposure to food and micro-organisms without causing deleterious immune responses. Changes in life-style, alterations in gut flora and use of antibiotics may be increasing disease prevalence. Mouse models of EoE and human studies revealed the role of regulatory T-cells and iNKT-cells in the pathogenesis. Th2-cytokines like IL-4, IL-5 and IL-13, and other cytokines like TGF帣 and TSLP are involved, but perhaps no one cytokine is critically important for driving the disease. Control of EoE may require a pharmaceutical approach that blocks more than one target in the Th2-inflammatory pathway. PMID:26552770

  7. Post-translational Tyrosine Nitration of Eosinophil Granule Toxins Mediated by Eosinophil Peroxidase*

    PubMed Central

    Ulrich, Martina; Petre, Alina; Youhnovski, Nikolay; Pr繹mm, Franziska; Schirle, Markus; Schumm, Michael; Pero, Ralph S.; Doyle, Alfred; Checkel, James; Kita, Hirohito; Thiyagarajan, Nethaji; Acharya, K. Ravi; Schmid-Grendelmeier, Peter; Simon, Hans-Uwe; Schwarz, Heinz; Tsutsui, Masato; Shimokawa, Hiroaki; Bellon, Gabriel; Lee, James J.; Przybylski, Michael; D繹ring, Gerd

    2008-01-01

    Nitration of tyrosine residues has been observed during various acute and chronic inflammatory diseases. However, the mechanism of tyrosine nitration and the nature of the proteins that become tyrosine nitrated during inflammation remain unclear. Here we show that eosinophils but not other cell types including neutrophils contain nitrotyrosine-positive proteins in specific granules. Furthermore, we demonstrate that the human eosinophil toxins, eosinophil peroxidase (EPO), major basic protein, eosinophil-derived neurotoxin (EDN) and eosinophil cationic protein (ECP), and the respective murine toxins, are post-translationally modified by nitration at tyrosine residues during cell maturation. High resolution affinity-mass spectrometry identified specific single nitration sites at Tyr349 in EPO and Tyr33 in both ECP and EDN. ECP and EDN crystal structures revealed and EPO structure modeling suggested that the nitrated tyrosine residues in the toxins are surface exposed. Studies in EPO-/-, gp91phox-/-, and NOS-/- mice revealed that tyrosine nitration of these toxins is mediated by EPO in the presence of hydrogen peroxide and minute amounts of NOx. Tyrosine nitration of eosinophil granule toxins occurs during maturation of eosinophils, independent of inflammation. These results provide evidence that post-translational tyrosine nitration is unique to eosinophils. PMID:18694936

  8. Diagnostic Approach to Eosinophilic Renal Neoplasms

    PubMed Central

    Kryvenko, Oleksandr N.; Jorda, Merce; Argani, Pedram; Epstein, Jonathan I.

    2015-01-01

    Context Eosinophilic renal neoplasms include a spectrum of solid and papillary tumors ranging from indolent benign oncocytoma to highly aggressive malignancies. Recognition of the correct nature of the tumor, especially in biopsy specimens, is paramount for patient management. Objective To review the diagnostic approach to eosinophilic renal neoplasms with light microscopy and ancillary techniques. Data Sources Review of the published literature and personal experience. Conclusions The following tumors are in the differential diagnosis of oncocytic renal cell neoplasm: oncocytoma, chromophobe renal cell carcinoma (RCC), hybrid tumor, tubulocystic carcinoma, papillary RCC, clear cell RCC with predominant eosinophilic cell morphology, follicular thyroid-like RCC, hereditary leiomyomatosisassociated RCC, acquired cystic diseaseassociated RCC, rhabdoid RCC, microphthalmia transcription factor translocation RCC, epithelioid angiomyolipoma, and unclassified RCC. In low-grade nonpapillary eosinophilic neoplasms, distinction between oncocytoma and low-grade RCC mostly rests on histomorphology; however, cytokeratin 7 immunostain may be helpful. In high-grade nonpapillary lesions, there is more of a role for ancillary techniques, including immunohistochemistry for cytokeratin 7, CA9, CD10, racemase, HMB45, and Melan-A. In papillary eosinophilic neoplasms, it is important to distinguish sporadic type 2 papillary RCC from microphthalmia transcription factor translocation and hereditary leiomyomatosisassociated RCC. Histologic and cytologic features along with immunohistochemistry and fluorescence in situ hybridization tests for TFE3 (Xp11.2) and TFEB [t(6;11)] are reliable confirmatory tests. Eosinophilic epithelial neoplasms with architecture, cytology, and/or immunoprofile not qualifying for either of the established types of RCC should be classified as unclassified eosinophilic RCC and arbitrarily assigned a grade (low or high). PMID:25357116

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

    MedlinePLUS

    ... Chronic lymphocytic leukemia (CLL) Acute myeloid leukemia (AML) Chronic myeloid leukemia (CML) About PLL and HCL There are other, less common types of leukemia, but they are generally subcategories of one ... both of which are types of chronic B-cell leukemia. B cells are a specific ...

  10. New Insights into Eosinophilic Otitis Media.

    PubMed

    Kanazawa, Hiromi; Yoshida, Naohiro; Iino, Yukiko

    2015-12-01

    Eosinophilic otitis media (EOM) is a type of intractable otitis media that occurs mainly in patients with bronchial asthma (BA). In 2011, the diagnostic criteria for EOM were established. EOM is characterized by the presence of a highly viscous yellowish effusion containing eosinophils and immunoglobulin E (IgE), eosinophil chemoattractants, such as eosinophil cationic protein, interleukin-5, and eotaxin. Local sensitization against foreign agents such as fungi or bacteria (e.g., Staphylococcus aureus) may result in local IgE production in the middle ear and may be responsible for the severity of EOM. The clinical features of EOM closely resemble localized eosinophilic granulomatosis polyangiitis, therefore it is necessary to be vigilant to the symptoms of mononeuritis, polyneuritis, and skin purpura during diagnosis. Standard treatment for EOM is the instillation of triamcinolone acetonide into the mesotympanum. However, severe cases exhibiting strong inflammation and otorrhea are not easily controlled with antibiotics and/or corticosteroids. We proposed the introduction of a severity score to evaluate the severity of EOM. This score correlated with local IgE levels in middle ear effusion. Clinically, the risk factors associated with this severity score were body mass index, and the duration of bronchial asthma (from the onset of BA to the age of the first consultation of otitis media to our hospital). We emphasize that early diagnosis and adequate treatment are vital in preventing progressive and sudden hearing loss resulting from EOM. PMID:26546407

  11. Does bee pollen cause to eosinophilic gastroenteropathy?

    PubMed

    G, Belgin Usta; Asilsoy, Suna; Canan, O?uz; Kayasel蓰k, Fazilet

    2015-09-01

    Bee pollen is given to children by mothers in order to strengthen their immune systems. There are no studies related with the side effects of bee polen in the literature. In this article, the literature was reviewed by presenting a case of allergic eosinophilic gastropathy related with bee polen. A 5-year old child was admitted due to abdominal pain. Edema was detected on the eyelids and pretibial region. In laboratory investigations, pathology was not detected in terms of hepatic and renal causes that would explain the protein loss of the patient diagnosed with hypoproteinemia and hypoalbuminemia. Urticaria was detected during the follow-up visit. When the history of the patient was deepened, it was learned that bee pollen was given to the patient every day. The total eosinophil count was found to be 1 800/mm(3). Allergic gastroenteropathy was considered because of hypereosinophilia and severe abdominal pain and endoscopy was performed. Biopsy revealed abundant eosinophils in the whole gastric mucosa. A diagnosis of allergic eosinophilic gastropathy was made. Bee polen was discontinued. Abdominal pain and edema disappeared in five days. Four weeks later, the levels of serum albumin and total eosinophil returned to normal. PMID:26568697

  12. Does bee pollen cause to eosinophilic gastroenteropathy?

    PubMed Central

    G羹癟, Belgin Usta; Asilsoy, Suna; Canan, Ouz; Kayasel癟uk, Fazilet

    2015-01-01

    Bee pollen is given to children by mothers in order to strengthen their immune systems. There are no studies related with the side effects of bee polen in the literature. In this article, the literature was reviewed by presenting a case of allergic eosinophilic gastropathy related with bee polen. A 5-year old child was admitted due to abdominal pain. Edema was detected on the eyelids and pretibial region. In laboratory investigations, pathology was not detected in terms of hepatic and renal causes that would explain the protein loss of the patient diagnosed with hypoproteinemia and hypoalbuminemia. Urticaria was detected during the follow-up visit. When the history of the patient was deepened, it was learned that bee pollen was given to the patient every day. The total eosinophil count was found to be 1 800/mm3. Allergic gastroenteropathy was considered because of hypereosinophilia and severe abdominal pain and endoscopy was performed. Biopsy revealed abundant eosinophils in the whole gastric mucosa. A diagnosis of allergic eosinophilic gastropathy was made. Bee polen was discontinued. Abdominal pain and edema disappeared in five days. Four weeks later, the levels of serum albumin and total eosinophil returned to normal. PMID:26568697

  13. Hairy Cell Leukemia Treatment

    MedlinePLUS

    ... Childhood ALL Treatment Childhood AML Treatment Research Hairy Cell Leukemia TreatmentPatient Version (PDQ簧) General Information About Hairy Cell Leukemia Key Points Hairy cell leukemia is a ...

  14. [FEATURES OF TREATMENT OF EOSINOPHILIC ESOPHAGITIS IN SCHOOLCHILDREN].

    PubMed

    Horodylovska, M I

    2015-01-01

    The inclusion of probiotic L. reuteri into the complex therapy of eosinophilic esophagitis significantly affect the outcomes of children--there was significant decrease in the number of eosinophils in the esophageal mucosa of children. PMID:26118052

  15. Roles and Regulation of Gastrointestinal Eosinophils in Immunity and Disease

    PubMed Central

    Jung, YunJae; Rothenberg, Marc E.

    2014-01-01

    Eosinophils have been considered to be destructive end-stage effector cells that have a role in parasitic infections and allergy reactions by the release of their granule-derived cytotoxic proteins. However, an increasing number of experimental observations indicate that eosinophils also are multifunctional leukocytes involved in diverse inflammatory and physiologic immune responses. Under homeostatic conditions, eosinophils are particularly abundant in the lamina propria of the gastrointestinal tract where their involvement in various biological processes within the gastrointestinal tract has been posited. In this review, we summarize the molecular steps involved in eosinophil development and describe eosinophil trafficking to the gastrointestinal tract. We synthesize the current findings on the phenotypic and functional properties of gastrointestinal eosinophils and the accumulating evidence that they have a contributory role in gastrointestinal disorders, with a focus on primary eosinophilic gastrointestinal disorders. Finally, we discuss the potential role of eosinophils as modulators of the intestinal immune system. PMID:25049430

  16. SOCS3 silencing attenuates eosinophil functions in asthma patients.

    PubMed

    Zafra, Ma Paz; Ca簽as, Jose A; Mazzeo, Carla; G獺mez, Cristina; Sanz, Veronica; Fern獺ndez-Nieto, Mar; Quirce, Santiago; Barranco, Pilar; Ruiz-Hornillos, Javier; Sastre, Joaqu穩n; del Pozo, Victoria

    2015-01-01

    Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process. PMID:25764157

  17. SOCS3 Silencing Attenuates Eosinophil Functions in Asthma Patients

    PubMed Central

    Zafra, M Paz; Ca鎙s, Jose A.; Mazzeo, Carla; G嫥ez, Cristina; Sanz, Veronica; Fern嫕dez-Nieto, Mar; Quirce, Santiago; Barranco, Pilar; Ruiz-Hornillos, Javier; Sastre, Joaqu璯; del Pozo, Victoria

    2015-01-01

    Eosinophils are one of the key inflammatory cells in asthma. Eosinophils can exert a wide variety of actions through expression and secretion of multiple molecules. Previously, we have demonstrated that eosinophils purified from peripheral blood from asthma patients express high levels of suppressor of cytokine signaling 3 (SOCS3). In this article, SOCS3 gene silencing in eosinophils from asthmatics has been carried out to achieve a better understanding of the suppressor function in eosinophils. SOCS3 siRNA treatment drastically reduced SOCS3 expression in eosinophils, leading to an inhibition of the regulatory transcription factors GATA-3 and FoxP3, also interleukin (IL)-10; in turn, an increased STAT3 phosphorilation was observed. Moreover, SOCS3 abrogation in eosinophils produced impaired migration, adhesion and degranulation. Therefore, SOCS3 might be regarded as an important regulator implicated in eosinophil mobilization from the bone marrow to the lungs during the asthmatic process. PMID:25764157

  18. Systematic review: Eosinophilic esophagitis in Asian countries

    PubMed Central

    Kinoshita, Yoshikazu; Ishimura, Norihisa; Oshima, Naoki; Ishihara, Shunji

    2015-01-01

    AIM: To investigate the prevalence and the clinical characteristics of Asian patients with eosinophilic esophagitis. METHODS: We conducted a systematic search of the PubMed and Web of Science databases for original studies, case series, and individual case reports of eosinophilic esophagitis in Asian countries published from January 1980 to January 2015. We found 66 and 80 articles in the PubMed and Web of Science databases, respectively; 24 duplicate articles were removed. After excluding animal studies, articles not written in English, and meeting abstracts, 25 articles containing 217 patients were selected for analysis. RESULTS: Sample size-weighted mean values were determined for all pooled prevalence data and clinical characteristics. The mean age of the adult patients with eosinophilic esophagitis was approximately 50 years, and 73% of these patients were male. They frequently presented with allergic diseases including bronchial asthma, allergic rhinitis, food allergy, and atopic dermatitis. Bronchial asthma was the most frequent comorbid allergic disease, occurring in 24% of patients with eosinophilic esophagitis. Dysphagia was the primary symptom reported; 44% of the patients complained of dysphagia. Although laboratory blood tests are not adequately sensitive for an accurate diagnosis of eosinophilic esophagitis, endoscopic examinations revealed abnormal findings typical of this disease, including longitudinal furrows and concentric rings, in 82% of the cases. One-third of the cases responded to proton pump inhibitor administration. CONCLUSION: The characteristics of eosinophilic esophagitis in Asian patients were similar to those reported in Western patients, indicating that this disease displays a similar pathogenesis between Western and Asian patients. PMID:26217096

  19. Mepolizumab in the treatment of severe eosinophilic asthma.

    PubMed

    Fainardi, Valentina; Pisi, Giovanna; Chetta, Alfredo

    2016-01-01

    IL-5 is crucial in the pathogenesis and evolution of eosinophilic asthma. Mepolizumab is a high-affinity humanized monoclonal antibody of the IgG1/k subtype that inhibits the binding of IL-5 to its receptor expressed on eosinophils, thereby inducing significant reduction in eosinophil circulation, as well as asthma exacerbations and corticosteroid treatment. This review deals with the currently available studies of mepolizumab in the treatment of patients with severe eosinophilic asthma. PMID:26653083

  20. [Eosinophilic cellulitis: About a new pediatric case].

    PubMed

    Makni, Saadia; Kallel, Rim; Chaab鋝e, Hend; Bahloul, Emna; Bahri, Ibtissem; Turki, Hamida; Gouiaa, Naourez; Boudawara, Tahya

    2015-12-01

    Wells' syndrome or "eosinophilic cellulitis" is characterized by clinical features of cellulitis and histological pictures of eosinophils infiltrate of the dermis with some flame figures. This is a very rare disease in the pediatric age. We report the case of a 14-month-old boy, presented with two farms painful nodular brownish lesions in the thigh and back of the foot as well as multiple erythematous papular and vesicular lesions on the forehead, cheeks, limbs and trunk. Biological analysis and histological examination confirmed the diagnosis of Wells' syndrome. The outcome was favorable with dermocorticoid. PMID:26586016

  1. Eosinophils mediate protective immunity against secondary nematode infection1

    PubMed Central

    Huang, Lu; Gebreselassie, Nebiat G.; Gagliardo, Lucille F.; Ruyechan, Maura C.; Luber, Kierstin L.; Lee, Nancy A.; Lee, James J.; Appleton, Judith A.

    2014-01-01

    Eosinophils are versatile cells that regulate innate and adaptive immunity, influence metabolism and tissue repair, and contribute to allergic lung disease. Within the context of immunity to parasitic worm infections, eosinophils are prominent yet highly varied in function. We have shown previously that when mice undergo primary infection with the parasitic nematode, Trichinella spiralis, eosinophils play an important, immune regulatory role that promotes larval growth and survival in skeletal muscle. In this study, we aimed to address the function of eosinophils in secondary infection with T. spiralis. By infecting eosinophil-ablated mice, we found that eosinophils are dispensable for immunity that clears adult worms or controls fecundity in secondary infection. In contrast, eosinophil ablation had a pronounced effect on secondary infection of skeletal muscle by migratory newborn larvae. Restoring eosinophils to previously infected, ablated mice caused them to limit muscle larvae burdens. Passive immunization of na簿ve, ablated mice with sera or immunoglobulin from infected donors, together with transfer of eosinophils, served to limit the number of newborn larvae that migrated in tissue and colonized skeletal muscle. Results from these in vivo studies are consistent with earlier findings that eosinophils bind to larvae in the presences of antibodies in vitro. Although our previous findings showed that eosinophils protect the parasite in primary infection, these new data show that eosinophils protect the host in secondary infection. PMID:25429065

  2. Generation of Eosinophils from Cryopreserved Murine Bone Marrow Cells

    PubMed Central

    Schollaert, Kaila L.; Stephens, Michael R.; Gray, Jerilyn K.; Fulkerson, Patricia C.

    2014-01-01

    Eosinophils are produced in the bone marrow from CD34+ eosinophil lineagecommitted progenitors, whose levels in the bone marrow are elevated in a variety of human diseases. These findings suggest that increased eosinophil lineagecommitted progenitor production is an important process in disease-associated eosinophilia. The pathways central to the biology of the eosinophil lineagecommitted progenitor remain largely unknown. Thus, developing new methods to investigate the regulators of eosinophil lineagecommitted progenitor differentiation is needed to identify potential therapeutic targets to specifically inhibit eosinophil production. We tested cytokine regimens to optimize liquid cultures for the study of eosinophil lineagecommitted progenitor and eosinophil precursor differentiation into mature eosinophils. Stem cell factor (but not fms-related tyrosine kinase 3 ligand) was required for optimal yield of eosinophils. Furthermore, we evaluated the effects of cell preservation and scale on the culture, successfully culturing functional eosinophils from fresh and frozen murine bone marrow cells and in a standard-sized and 96-well culture format. In summary, we have developed an adaptable culture system that yields functionally competent eosinophils from murine low-density bone marrow cells and whose cytokine regime includes expansion of progenitors with stem cell factor alone with subsequent differentiation with interleukin 5. PMID:25551463

  3. EOSINOPHILS: MULTIFACETED BIOLOGIC PROPERTIES AND ROLES IN HEALTH AND DISEASE

    PubMed Central

    Kita, Hirohito

    2011-01-01

    Summary Eosinophils are leukocytes resident in mucosal tissues. During Th2-type inflammation, eosinophils are recruited from bone marrow and blood to the sites of immune response. While eosinophils have been considered end-stage cells involved in host protection against parasite infection and immunopathology in hypersensitivity disease, recent studies changed this perspective. Eosinophils are now considered multifunctional leukocytes involved in tissue homeostasis, modulation of adaptive immune responses, and innate immunity to certain microbes. Eosinophils are capable of producing immunoregulatory cytokines and are actively involved in regulation of Th2-type immune responses. However, such new information does not preclude earlier observations showing that eosinophils, in particular human eosinophils, are also effector cells with pro-inflammatory and destructive capabilities. Eosinophils with activation phenotypes are observed in biological specimens from patients with disease, and deposition of eosinophil products is readily seen in the affected tissues from these patients. Therefore, it would be reasonable to consider the eosinophil a multifaceted leukocyte that contributes to various physiological and pathological processes depending on their location and activation status. This review summarizes the emerging concept of the multifaceted immunobiology of eosinophils and discusses the roles of eosinophils in health and disease and the challenges and perspectives in the field. PMID:21682744

  4. Antiallergic and antiasthmatic effects of a novel enhydrazinone ester (CEE-1): inhibition of activation of both mast cells and eosinophils.

    PubMed

    Ezeamuzie, Charles I; El-Hashim, Ahmed Z; Renno, Waleed M; Edafiogho, Ivan O

    2014-08-01

    Activation of mast cells and eosinophils is a fundamental process in the pathophysiology of allergic diseases. We have previously reported that the novel enhydrazinone ester CEE-1 (ethyl 4-phenylhydrazinocyclohex-3-en-2-oxo-6-phenyl-1-oate) possesses potent anti-inflammatory activity. We have now tested whether the compound also possesses antiallergic and antiasthmatic effects in vitro and in vivo. The compound significantly inhibited degranulation and leukotriene C4 (LTC4) release from activated human eosinophils, as well as IgE-dependent degranulation and LTC4 release from passively sensitized rat basophilic leukemia cells and bone marrow-derived mouse mast cells. In human eosinophils, the drug was more potent in inhibiting degranulation than LTC4 release {IC50 = 0.4 ?M [confidence interval (CI): 0.1-0.9] versus 3.8 ?M (CI: 0.9-8.3)}, whereas in mast cells the reverse was essentially the case. The drug did not affect stimulus-induced calcium transients in eosinophils but significantly inhibited early phosphorylation of extracellular signal-regulated kinases 1/2 and p38-mitogen-activated protein kinases (MAPK). In vivo, topical application of 4.5-15 mg/kg of the compound significantly inhibited allergen-induced passive cutaneous anaphylaxis in mice. Similarly, in the mouse asthma model, the intranasal administration of 6.5-12.5 mg/kg of the compound significantly inhibited bronchial inflammation and eosinophil accumulation in bronchial lavage fluid, as well as abolishing airway hyper-responsiveness to methacholine. These results show that CEE-1 inhibits the activation of both mast cells and eosinophils in vitro, probably by blocking MAPK-activation pathways, and that these effects are translated into antiallergic and antiasthmatic effects in vivo. The compound, therefore, has potential application in the treatment of asthma and other allergic diseases. PMID:24917545

  5. Childhood Cancer: Leukemia (For Parents)

    MedlinePLUS

    ... Other types of leukemia, like chronic myelogenous leukemia (CML) or juvenile myelomonocytic leukemia (JMML) , are much less ... Leukemia (ALL) Chemotherapy Radiation Therapy Chronic Myelogenous Leukemia (CML) Cancer Center Acute Myeloid Leukemia (AML) Juvenile Myelomonocytic ...

  6. The early history of the eosinophil.

    PubMed

    Kay, A B

    2015-03-01

    In 1879 Paul Ehrlich published his technique for staining blood films and his method for differential blood cell counting using coal tar dyes and mentions the eosinophil for the first time. Eosin is a bright red synthetic dye produced by the action of bromine on fluorescein and stains basic proteins due to its acidic nature. It was discovered in 1874 by Heinrich Caro, Director of the German chemical company Badische Anilin- und Soda-Fabrik. Ehrlich introduced the term 'eosinophil' to describe cells with granules (which he called alpha-granules) having an affinity for eosin and other acid dyes. He also observed black-staining, indulinophilic, beta-granules in bone marrow-derived eosinophils, which were probably immature crystalloid granules in eosinophil myelocytes. Ehrlich described the features of the alpha-granule and the cell's distribution in various species and tissues. He speculated correctly that the alpha-granule contents were secretory products and described several causes of eosinophilia including asthma, various skin diseases, helminths and reactions to medications. However, the cell was almost certainly observed by others before Ehrlich. In 1846 Thomas Wharton Jones (1808-1891) described 'granule blood cells' in the lamprey, frog, fowl, horse, elephant and man. He 'borrowed' the term granule cell from Julius Vogel (1814-1880) who had observed similar cells in inflammatory exudates. Vogel in turn was aware of the work of the Gottlieb (Th矇ophile) Gluge (1812-1898) who used the term 'compound inflammatory globules' to describe cells in pus and serum. Almost 20years before Ehrlich developed his staining methods, Max Johann Sigismund Schultze (1825-1874) performed functional experiments on coarse granular cells using a warm stage microscopic technique and showed they had amoeboid movement and phagocytic abilities. Although these early investigators recognised distinct granular cells Ehrlich's use of stains was a landmark contribution, which heralded modern studies on eosinophils and other blood leucocytes. PMID:25544991

  7. Leukotriene B4 amplifies eosinophil accumulation in response to nematodes

    PubMed Central

    Patnode, Michael L.; Bando, Jennifer K.; Krummel, Matthew F.; Locksley, Richard M.

    2014-01-01

    Eosinophil accumulation is a defining feature of the immune response to parasitic worm infection. Tissue-resident cells, such as epithelial cells, are thought to initiate eosinophil recruitment. However, direct recognition of worms by eosinophils has not been explored as a mechanism for amplifying eosinophil accumulation. Here, we report that eosinophils rapidly migrate toward diverse nematode species in three-dimensional culture. These include the mammalian parasite Nippostrongylus brasiliensis and the free-living nematode Caenorhabditis elegans. Surprisingly, collective migration toward worms requires paracrine leukotriene B4 signaling between eosinophils. In contrast, neutrophils show a minimal response to nematodes, yet are able to undergo robust leukotriene-dependent migration toward IgG-coated beads. We further demonstrate that eosinophils accumulate around C. elegans in the lungs of mice. This response is not dependent on bacterial products, CCR3, or complement activation. However, mice deficient in leukotriene signaling show markedly attenuated eosinophil accumulation after injection of C. elegans or N. brasiliensis. Our findings establish that nematode-derived signals can directly induce leukotriene production by eosinophils and that leukotriene signaling is a major contributor to nematode-induced eosinophil accumulation in the lung. The similarity of the eosinophil responses to diverse nematode species suggests that conserved features of nematodes are recognized during parasite infection. PMID:24889202

  8. ATP drives eosinophil effector responses through P2 purinergic receptors

    PubMed Central

    Kobayashi, Takehito; Soma, Tomoyuki; Noguchi, Toru; Nakagome, Kazuyuki; Nakamoto, Hidetomo; Kita, Hirohito; Nagata, Makoto

    2015-01-01

    Background Eosinophils recognize various stimuli, such as cytokines, chemokines, immunoglobulins, complement, and external pathogens, resulting in their accumulation in mucosal tissues and the progression of inflammation. Eosinophils are also involved in innate Th2-type immune responses mediated through endogenous danger signals, including IL-33, uric acid (UA), or ATP, in non-sensitized mice exposed to environmental allergens. However, the mechanism involved in eosinophil responses to these danger signals remains insufficiently understood. Methods We examined migration, adhesion, superoxide production and degranulation of human eosinophils. Isolated eosinophils were incubated with monosodium urate (MSU) crystals and ATP帠S, a nonhydrolysable ATP analogue. To determine the involvement of P2 or P2Y2 receptors in eosinophil responses to UA and ATP, eosinophils were preincubated with a pan-P2 receptor inhibitor, oxidized ATP (oATP), or anti-P2Y2 antibody before incubation with MSU crystals or ATP帠S. Results MSU crystals induced adhesion of eosinophils to recombinant human (rh)-ICAM-1 and induced production of superoxide. oATP abolished eosinophil responses to MSU crystals, suggesting involvement of endogenous ATP and its receptors. Furthermore, exogenous ATP, as ATP帠S, induced migration of eosinophils through a model basement membrane, adhesion to rh-ICAM-1, superoxide generation, and degranulation of eosinophil-derived neurotoxin (EDN). oATP and anti-P2Y2 significantly reduced these eosinophil responses. Conclusions ATP serves as an essential mediator of functional responses in human eosinophils. Eosinophil responses to ATP may be implicated in airway inflammation in patients with asthma. PMID:26344078

  9. [Eosinophilic gastroenteritis and ascites. Clinical case].

    PubMed

    Ottobrelli, A; Lagget, M; Arrigoni, A; Gindro, T; Bosio, C; Balbo, G; Rizzetto, M

    1991-01-01

    We report the case of a patient with recurrent subocclusive episodes and diarrhea (no malabsorption) associated with ascites, in the absence or liver, kidney or heart disease. The demonstration of hypereosinophilia in the peripheral blood and in the ascites fluid and the failure to identify parasitic or haematological disorders have led to a through examination of the stomach (Endoscopy, Echoendoscopy), small bowel (X-rays and Computerized Axial Tomography) and colon (colonoscopy) in a search for parietal lesions. The absence of segmental lesions and the observation of CAT images of diffuse, regular thickening of the ileum and of the mesentery, coupled with the monotonous clinical history spanning over three decades, have led to a diagnosis of eosinophilic gastroenteritis with involvement of the serosal layer. Serosal involvement is rare in eosinophilic disease of the gut; in analogy with other cases reported in the literature, steroids have improved clinical symptoms and normalized the hematological picture. PMID:1742398

  10. [Eosinophilic esophagitis, a pathology on the rise].

    PubMed

    Miranda Garc燰, M; Guti廨rez Teira, B

    2013-10-01

    The eosinophilic esofagitis is a pathology that consists of an inflammatory condition of the esophagus, which is characterized for having a high percentage of eosinophils. It is a problem of allergic origin and his diagnosis is increasing in the population, especially in children and adult young persons, throughout last decade. The fisiopathology is not completely established nowadays. The diagnosis is confirmed with endoscopia and capture of biopsies. The differential diagnosis is necessary to be done with the disease for reflux gastroesof墔ico, gastroenteritis eosinof璱ica, by Crohn's disease, pathology of connective fabric, syndrome hipereosinof璱ico, infections and response of hypersensitivity to medicaments. Nowadays there is no a treatment that is definitive. We present a clinical case, which was valued initially for the consultation of Primary care. PMID:24095173

  11. Into the wild world of eosinophilic granuloma

    PubMed Central

    Dhull, Anil Kumar; Aggarwal, Sumeet; Kaushal, Vivek; Singh, Sunita

    2013-01-01

    Langerhans cell histiocytosis (LCH) is a group of relatively rare disease processes of reticuloendothelial system with an abnormal proliferation of Langerhans cells or their precursors. A wide spectrum of treatment modalities is available for LCH which includes surgery, curettage, steroids, radiation, various chemotherapy regimens, either in combination or alone have so far been adopted. There are several case reports of eosinophilic granuloma but for recurrent cases very few have discussed on treatment of LCH in adults. We report a case of a 21-year-old man presented with eosinophilic granuloma with recurrence of the lesions after 6?years of the initial treatment. Patient was treated with combination chemotherapy with three weekly CHOP regimen and the patient is disease free after 6?months of follow-up. Contrary to other reports, this case demonstrates that a good response with standard therapy is possible. PMID:24252836

  12. GWAS identifies four novel eosinophilic esophagitis loci

    PubMed Central

    Sleiman, Patrick MA; Wang, Mei-Lun; Cianferoni, Antonella; Aceves, Seema; Gonsalves, Nirmala; Nadeau, Kari; Bredenoord, Albert J.; Furuta, Glenn T.; Spergel, Jonathan M.; Hakonarson, Hakon

    2014-01-01

    Eosinophilic esophagitis (EoE) is an allergic disorder characterized by infiltration of the esophagus with eosinophils. We had previously reported association of the TSLP/WDR36 locus with EoE. Here we report genome-wide significant associations at four additional loci; c11orf30 and STAT6, which have been previously associated with both atopic and autoimmune disease, and two EoE-specific loci, ANKRD27 that regulates the trafficking of melanogenic enzymes to epidermal melanocytes and CAPN14, that encodes a calpain whose expression is highly enriched in the esophagus. The identification of five EoE loci, not only expands our etiological understanding of the disease but may also represent new therapeutic targets to treat the most debilitating aspect of EoE, esophageal inflammation and remodeling. PMID:25407941

  13. Strongyloides stercoralis hyperinfection causing eosinophilic ascites.

    PubMed

    Shukla, Shailaja; Chauhan, Richa; Wadhwa, Shveta; Sehgal, Shivali; Singh, Smita

    2015-09-01

    Strongyloidiasis is associated with Strongyloides stercoralis, an intestinal nematode with greater prevalence in tropical and subtropical regions. Hyperinfection syndrome with dissemination may occur in immunosuppressed individuals. However, invasion of peritoneal cavity with peritoneal effusion is rarely reported in the literature. We report a case of S. stercoralis hyperinfection in a young alcoholic patient with Diabetes mellitus, liver disease and ascites. Diagnostic paracentesis showed numerous filariform larvae of S. stercoralis against a background of eosinophils. PMID:26097138

  14. Significance of feeding dysfunction in eosinophilic esophagitis

    PubMed Central

    Menard-Katcher, Calies; Henry, Michelle; Furuta, Glenn T; Atkins, Dan; Maune, Nancy Creskoff; Haas, Angela M

    2014-01-01

    Feeding dysfunction is a frequent presenting symptom of eosinophilic esophagitis (EoE). Here we present 3 children of various ages whose manifestations of EoE associated feeding dysfunction led to significant and life altering impact on their growth and development. Early identification of presenting symptoms of EoE will allow for prompt diagnosis and initiation of appropriate treatments. Recognition of salient features of dysfunction and treatment by feeding therapists and nutritionists led to symptom resolution and growth. PMID:25152606

  15. Eyelid eosinophilic granuloma in a Siberian husky.

    PubMed

    Vercelli, A; Cornegliani, L; Portigliotti, L

    2005-01-01

    Canine eosinophilic granuloma (CEG) is a rare skin disease of unknown origin. It has been reported in Siberian huskies, Cavalier King Charles spaniels and occasionally in other breeds. The lesions comprise nodules or plaques, mostly localised in the oral cavity. A case of a single cutaneous nodular lesion of CEG on the eyelid of a Siberian husky is described. Complete remission was achieved with oral glucocorticoid treatment. PMID:15682738

  16. Significance of feeding dysfunction in eosinophilic esophagitis.

    PubMed

    Menard-Katcher, Calies; Henry, Michelle; Furuta, Glenn T; Atkins, Dan; Maune, Nancy Creskoff; Haas, Angela M

    2014-08-21

    Feeding dysfunction is a frequent presenting symptom of eosinophilic esophagitis (EoE). Here we present 3 children of various ages whose manifestations of EoE associated feeding dysfunction led to significant and life altering impact on their growth and development. Early identification of presenting symptoms of EoE will allow for prompt diagnosis and initiation of appropriate treatments. Recognition of salient features of dysfunction and treatment by feeding therapists and nutritionists led to symptom resolution and growth. PMID:25152606

  17. Treatment Adherence in Pediatric Eosinophilic Gastrointestinal Disorders

    PubMed Central

    Franciosi, James P.; Hente, Elizabeth A.; Ahrens, Annette; Rothenberg, Marc E.

    2012-01-01

    ObjectiveExamine treatment adherence rates in pediatric eosinophilic gastrointestinal disorders (EGID).MethodsParticipants were children aged 2.518 years with eosinophilic esophagitis or eosinophilic gastroenteritis (EGE) and their caregivers. A multimethod, multi-informant assessment including parent report and electronic monitoring was utilized, with a 90% cut point for nonadherence.ResultsMedication nonadherence prevalence was 30%. Adherence frequency was 91%簣14% (0100%) per parent report and 100%簣69% (0194%) per electronic monitors. Tube-feeding adherence was 99%簣3%. Food allergen exposures were less than 1 per 2 weeks, with 33% nonadherence prevalence. Patients with EGE and toddlers with both conditions demonstrated poorer medication adherence (ps<.05). Caregivers reported higher number of missed medication doses than food exposures (p<.05).ConclusionsThe prevalence and range of nonadherence demonstrates that subsets of these patients are nonadherent. Adherence to treatment in EGID is complex and multifaceted, with nonadherence varying across treatments. PMID:22080457

  18. Eosinophilic oesophagitis: clinical presentation and pathogenesis

    PubMed Central

    Bystrom, Jonas; O'Shea, Nuala R

    2014-01-01

    Eosinophilic oesophagitis (EoE) is an inflammatory disorder of the oesophagus which has become increasingly recognised over recent years, although it remains underdiagnosed in many centres. It is characterised histologically by a significant eosinophilic infiltration of the oesophageal mucosa (>15 eosinophils per high powered field), and clinically with features of oesophageal dysfunction such a dysphagia, food impaction, and proton pump inhibitor (PPI) resistant dyspepsia. Fibrosis and oesophageal remodelling may occur and lead to oesophageal strictures. An allergic predisposition is common in the EoE population, which appears to be primarily food antigen driven in children and aeroallergen driven in adults. Evidence suggests that the pathogenesis of EoE is due to a dysregulated immunological response to an environmental allergen, resulting in a T helper type 2 (Th2) inflammatory disease and remodelling of the oesophagus in genetically susceptible individuals. Allergen elimination and anti-inflammatory therapy with corticosteroids are currently the mainstay of treatment; however, an increasing number of studies are now focused on targeting different stages in the disease pathogenesis. A greater understanding of the underlying mechanisms resulting in EoE will allow us to improve the therapeutic options available. PMID:24647582

  19. Association of eosinophilic fasciitis with morphea.

    PubMed

    Zisova, Lilia G; Abadjieva, Tsvetana I; Abadjieva, Cvetana I; Obreshkova, Elena V; Tchernev, Georgi K; Chernev, Georgi K; Vutova, Nina I

    2014-01-01

    Eosinophilic fasciitis is a rare inflammatory disease of unknown etiology, described for the first time by Shulman in 1974. The disease presents with induration of the skin, connective tissue and the underlying muscle fascia, sometimes accompanied by myalgia, most commonly in the lower extremities. Unlike scleroderma, it presents with absence of visceral organ involvement and Raynaud's phenomenon. Hypergammaglobulinemia and eosinophilia have been reported. Eosinophilic fasciitis is often associated with hematological disorders--there are reports of combinations with other autoimmune diseases such as systemic sclerosis, systemic lupus erythematosus, Hashimoto thyroiditis, Sjogren syndrome, vitiligo, etc. Occurrence of morphea, in the course of eosinophil fasciitis is considered a rarity. We have observed such a case with the simultaneous presence of both types of lesions. A 20-year-old female patient is reported, wherein the clinical picture developed for 6 months. The initial erythematous edema and subsequently the livedo-like painful plaques in both lower legs gradually swell, thicken and hyperpigment. Almost simultaneously with these complaints small brown livid body plaques emerged. The patient was diagnosed based on history, clinical picture, peripheral eosinophilia and histological findings from the affected areas. There was no systemic involvement and accompanying hematologic or other disease. Therapeutic management and significant clinical improvement were achieved using systemic corticosteroid therapy combined with methotrexate. PMID:25434081

  20. Eosinophils are necessary for pulmonary arterial remodeling in a mouse model of eosinophilic inflammation-induced pulmonary hypertension.

    PubMed

    Weng, M; Baron, D M; Bloch, K D; Luster, A D; Lee, J J; Medoff, B D

    2011-12-01

    There is increasing evidence that inflammation plays a pivotal role in the pathogenesis of some forms of pulmonary hypertension (PH). We recently demonstrated that deficiency of adiponectin (APN) in a mouse model of PH induced by eosinophilic inflammation increases pulmonary arterial remodeling, pulmonary pressures, and the accumulation of eosinophils in the lung. Based on these data, we hypothesized that APN deficiency exacerbates PH indirectly by increasing eosinophil recruitment. Herein, we examined the role of eosinophils in the development of inflammation-induced PH. Elimination of eosinophils in APN-deficient mice by treatment with anti-interleukin-5 antibody attenuated pulmonary arterial muscularization and PH. In addition, we observed that transgenic mice that are devoid of eosinophils also do not develop pulmonary arterial muscularization in eosinophilic inflammation-induced PH. To investigate the mechanism by which APN deficiency increased eosinophil accumulation in response to an allergic inflammatory stimulus, we measured expression levels of the eosinophil-specific chemokines in alveolar macrophages isolated from the lungs of mice with eosinophilic inflammation-induced PH. In these experiments, the levels of CCL11 and CCL24 were higher in macrophages isolated from APN-deficient mice than in macrophages from wild-type mice. Finally, we demonstrate that the extracts of eosinophil granules promoted the proliferation of pulmonary arterial smooth muscle cells in vitro. These data suggest that APN deficiency may exacerbate PH, in part, by increasing eosinophil recruitment into the lung and that eosinophils could play an important role in the pathogenesis of inflammation-induced PH. These results may have implications for the pathogenesis and treatment of PH caused by vascular inflammation. PMID:21908591

  1. Experimental production of pulmonary granulomas. IV. Eosinophilic granuloma.

    PubMed Central

    Hamamoto, Y.; Kinoshita, K.; Hashimoto, K.; Matsushita, T.; Kogishi, K.; Yasuhira, K.

    1983-01-01

    Pulmonary granulomas induced in rabbits by the endobronchial instillation of mycobacterial chemical fractions were re-examined for eosinophilic infiltration. Delayed type hypersensitivity reactions either of tuberculin type or of wax D type did not induce but rather suppressed eosinophilic infiltration in the inflamed area, although some peptidoglycans which are antigenic for the induction of immediate hypersensitivity and fatty acid fractions were weak stimulators of eosinophilic infiltration. Bacterial endotoxin, LPS, was a potent stimulator. It was found that some long chain fatty acids can cause severe eosinophilic infiltration in the induced granulomas. Arachidonic acid was the most active of those examined, so the activity of its metabolites was tested and PGE2 was found to be most active. As the eosinophilic infiltration was markedly suppressed in animals treated with a cyclooxygenase inhibitor (aspirin), the stimulators of eosinophilic infiltration were not fatty acids themselves but their metabolites, PGE2 and some others. The site of permeation of eosinophils from the circulation was found to be arteriolar in the inflamed lung. The granulomatous lesion with eosinophilic infiltration in rabbits is discussed to shed light on the aetiology of eosinophilic granuloma in the human lung. Images Fig. 1 Fig. 2 Fig. 3 and 4 Fig. 5 Fig. 6 Fig. 7 Fig. 8 Fig. 9 and 10 PMID:6849813

  2. Diagnosing Eosinophilic Colitis: Histopathological Pattern or Nosological Entity?

    PubMed Central

    Bates, Alan W. H.

    2012-01-01

    Reports of eosinophilic colitisraised colonic mucosal eosinophil density in patients with lower gastrointestinal symptomshave increased markedly over the last fifteen years, though it remains a rarity. There is no consensus over its diagnosis and management, and uncertainty is compounded by the use of the same term to describe an idiopathic increase in colonic eosinophils and an eosinophilic inflammatory reaction to known aetiological agents such as parasites or drugs. In patients with histologically proven colonic eosinophilia, it is important to seek out underlying causes and careful clinicopathological correlation is advised. Because of the variability of eosinophil density in the normal colon, it is recommended that histological reports of colonic eosinophilia include a quantitative morphometric assessment of eosinophil density, preferably across several sites. Few reported cases of eosinophilic colitis meet these criteria. As no correlation has been shown between colonic eosinophil density and symptoms in older children or adults, it is suggested that treatment should be directed towards alleviation of symptoms and response to treatment assessed clinically rather than by histological estimates of intramucosal eosinophils. PMID:24278727

  3. [Eosinophilic granuloma of the oral cavity in a Siberian husky].

    PubMed

    Vermond, J F; Koedam, M A

    1989-01-15

    An ulcerative sublingual inflammation was found to be present in a Siberian Husky dog. Histological examination revealed an eosinophilic granuloma. Treatment with corticosteroids was successful. PMID:2919392

  4. Acute Lymphoblastic Leukemia (ALL)

    MedlinePLUS

    ... this page Print this page Acute lymphoblastic leukemia (ALL) Acute lymphoblastic leukemia (ALL) is a fast-growing cancer of a type ... that your body needs. Tweet Acute Lymphoblastic Leukemia (ALL) Transplant outcomes for ALL Initial treatment of ALL ...

  5. Chronic myelogenous leukemia (CML)

    MedlinePLUS

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Cause of CML is related to an abnormal chromosome called the Philadelphia chromosome. Radiation exposure can increase the risk of developing ...

  6. Homologous recombination into the eosinophil peroxidase locus generates a strain of mice expressing Cre recombinase exclusively in eosinophils

    PubMed Central

    Doyle, Alfred D.; Jacobsen, Elizabeth A.; Ochkur, Sergei I.; Willetts, Lian; Shim, Kelly; Neely, Joseph; Kloeber, Jake; LeSuer, Will E.; Pero, Ralph S.; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A.; Lee, James J.

    2013-01-01

    Eosinophils are generally linked to innate host defense against helminths, as well as the pathologies associated with allergic diseases, such as asthma. Nonetheless, the activities of eosinophils remain poorly understood, which in turn, has prevented detailed definitions of their role(s) in health and disease. Homologous recombination in embryonic stem cells was used to insert a mammalianized Cre recombinase in the ORF encoding Epx. This knock-in strategy overcame previous inefficiencies associated with eosinophil-specific transgenic approaches and led to the development of a knock-in strain of mice (eoCRE), capable of mediating recombination of floxed reporter cassettes in >95% of peripheral blood eosinophils. We also showed that this Cre expression was limited exclusively to eosinophil-lineage committed cells with no evidence of Cre-mediated toxicity. The efficiency and specificity of Cre expression in eoCRE mice were demonstrated further in a cross with a knock-in mouse containing a (flox-stop-flox) DTA cassette at the ROSA26 locus, generating yet another novel, eosinophil-less strain of mice. The development of eoCRE mice represents a milestone in studies of eosinophil biology, permitting eosinophil-specific gene targeting and overexpression in the mouse as part of next-generation studies attempting to define eosinophil effector functions. PMID:23630390

  7. Targeting AMCase reduces esophageal eosinophilic inflammation and remodeling in a mouse model of egg induced eosinophilic esophagitis

    PubMed Central

    Cho, Jae Youn; Rosenthal, Peter; Miller, Marina; Pham, Alexa; Aceves, Seema; Sakuda, Shohei; Broide, David H

    2014-01-01

    Studies of AMCase inhibition in mouse models of lung eosinophilic inflammation have produced conflicting results with some studies demonstrating inhibition of eosinophilic inflammation and others not. No studies have investigated the role of AMCase inhibition in eosinophilic esophagitis (EoE). We have used a mouse model of egg (OVA) induced EoE to determine whether pharmacologic inhibition of AMCase with allosamidin reduced eosinophilic inflammation and remodeling in the esophagus in EoE. Administration of intra-esophageal OVA for 6 weeks to BALB/c mice induced increased levels of esophageal eosinophils, mast cells, and features of esophageal remodeling (fibrosis, basal zone hyperplasia, deposition of the extracellular matrix protein fibronectin). Administration of intraperitoneal (ip) allosamidin to BALB/c mice significantly inhibited AMCase enzymatic activity in the esophagus. Pharmacologic inhibition of AMCase with ip allosamidin inhibited both OVA induced increases in esophageal eosinophilic inflammation and OVA induced esophageal remodeling (fibrosis, epithelial basal zone hyperplasia, extracellular matrix deposition of fibronectin). This inhibition of eosinophilic inflammation in the esophagus by ip allosamidin was associated with reduced eotaxin-1 expression in the esophagus. Oral allosamidin inhibited eosinophilic inflammation in the epithelium but did not inhibit esophageal remodeling. These studies suggest that pharmacologic inhibition of AMCase results in inhibition of eosinophilic inflammation and remodeling in the esophagus in a mouse model of egg induced EoE partially through effects in the esophagus on reducing chemokines (i.e. eotaxin-1) implicated in the pathogenesis of EoE. PMID:24239745

  8. Reversible Severe Eosinophilic Endomyocardial Fibrosis During Pregnancy

    PubMed Central

    Pineton de Chambrun, Marc; Charron, Philippe; Vauthier-Brouzes, Dani鋩e; Cluzel, Philippe; Haroche, Julien; Kahn, Jean-Emmanuel; Amoura, Zahir; Aubart, Fleur Cohen

    2015-01-01

    Abstract Idiopathic hypereosinophilic syndrome (HES) is a condition of unknown origin characterized by clinical manifestations attributable to eosinophilia and eosinophilic infiltration of tissues. Cardiac involvement is rare and threatening accounting for 33% to 43% of death in HES. Management of pregnant patients with HES is challenging and have rarely been reported, particularly in the setting of heart failure. We here report on the case of a 29-year-old woman with HES who developed severe endomyocardial fibrosis with heart failure during pregnancy. Outcome was favorable under treatment with prednisone and azathioprine. This case illustrates a favorable outcome of endomyocardial fibrosis during pregnancy. PMID:26266372

  9. Eosinophilic panniculitis in a female child: An unusual presentation

    PubMed Central

    Jain, Sonia; Jain, Pramod; Jakhar, Preeti; Shivkumar, V. B.

    2015-01-01

    Eosinophilic panniculitis (EP) is characterized by prominent infiltration of subcutaneous fat with eosinophils. The etiology is diverse. This is not a disease but represents a reaction pattern that may occur in a variety of circumstances. The exact pathogenesis of the disease is still unclear. We present the case of a 6-year-old girl child who was diagnosed with EP. PMID:25657915

  10. Steroid responsive eosinophilic gastric outlet obstruction in a child

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Gastric outlet obstruction is a rare complication of eosinophilic gastroenteritis, most commonly treated surgically. We report a case of eosinophilic gastric outlet obstruction in a child that responded to conservative medical management. A brief review of this clinical entity is also provided....

  11. EOSINOPHILIC MYOSITIS DUE TO SARCOCYSTIS HOMINIS IN A BEEF COW

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A case of eosinophilic myositis in an eight-year-old beef cow was investigated. The cow originated from a herd that had a high incidence of eosinophilic myositis in slaughtered adult females during a period of two years. Histologically, the lesions in the muscles were characterized as granulomas wit...

  12. Intranuclear crystalloids associated with abnormal granules in eosinophilic leukocytes

    SciTech Connect

    Parmley, R.T.; Crist, W.M.; Roper, M.; Takagi, M.; Austin, R.L.

    1981-12-01

    Ultrastructural evaluation of eosinophilic leukocytes from a 2-yr-old asymptomatic girl with chronic benign neutropenia (CBN) revealed a variety of morphological abnormalities. All eosinophils obtained from blood and marrow specimens contained multiple microcrystalloids in most of the mature cytoplasmic granules. An increase in crystalloid-free, immature granules in late (bilobed nuclei) eosinophils suggested a delay in granule maturation. The eosinophil granules appeared to be of normal size and demonstrated normal acid phosphatase reactivity. Eosinophilic myelocytes contained abnormal cisternae of rough endoplasmic reticulum (RER) and lacked abundant elongated RER cisternae seen in normal cells. A few eosinophilic myelocytes in specimens of bone marrow from the child contained large intranuclear crystalloids measuring up to 3 mu in length. The intranuclear crystalloid contained as cubic lattice of dense material with a periodicity similar to that described for cytoplasmic crystalloids. The ultrastructural morphology of marrow neutrophils was normal, as described in other cases of CBN. Ultrastructural examination of blood eosinophils from the father demonstrated microcrystalloids in cytoplasmic granules identical to those seen in the child. The father was asymptomatic and had normal leukocyte counts. Thus, anomalous crystalloid granule genesis occurred in the father and daughter and was not necessarily associated with neutropenia or clinical symptomatology. This anomaly is associated with the accumulation of intranuclear crystalloid material in eosinophilic myelocytes, which do not appear to be released from the marrow compartment.

  13. Gut reactions: Eosinophils add another string to their bow.

    PubMed

    Sutherland, Duncan B; Fagarasan, Sidonia

    2014-04-17

    Eosinophils are found in abundance in the gut. In this issue of Immunity, Chu et al. (2014) report that eosinophil-deficient mice have impaired intestinal immunoglobulin A production, accompanied by a disrupted mucosal layer and alterations in microbiota density and composition. PMID:24745328

  14. An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock

    PubMed Central

    Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P.

    2015-01-01

    Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration. PMID:26078733

  15. An Atypical Case of Eosinophilic Gastroenteritis Presenting as Hypovolemic Shock.

    PubMed

    Martillo, Miguel; Abed, Jean; Herman, Michael; Abed, Elie; Shi, Wenjing; Munot, Khushboo; Mankal, Pavan Kumar; Gurunathan, Rajan; Ionescu, Gabriel; Kotler, Donald P

    2015-01-01

    Eosinophilic gastroenteritis is an uncommon condition characterized by focal or diffuse infiltration of eosinophils in the gastrointestinal tract in the absence of secondary causes. The pathogenesis of this condition is not well understood and its clinical presentation depends on the segment and layer of the gastrointestinal tract affected. The definition of eosinophilic gastroenteritis may be difficult, as the normal ranges of eosinophil numbers in normal and abnormal gastric and intestinal mucosa are not standardized. We present the case of a 59-year-old male who came to the hospital with hypovolemic shock and lethargy secondary to severe diarrhea. Laboratory analysis was significant for peripheral eosinophilia, and pathology from both the duodenum and colon showed marked eosinophilic infiltration. PMID:26078733

  16. HIV-associated eosinophilic folliculitis in an infant.

    PubMed

    Ramdial, P K; Morar, N; Dlova, N C; Aboobaker, J

    1999-06-01

    HIV-associated eosinophilic folliculitis (HIV-EF), which is a well-known entity in adults, has not been described in children. Although Ofuji's disease (OD) or eosinophilic pustular folliculitis (EPF) has been described in children and shares histopathologic features with HIV-EF, it is a distinct entity with characteristic clinical features. We report the occurrence of eosinophilic folliculitis in an 8-month-old HIV-positive patient and discuss the clinical, pathologic and possible pathogenetic aspects thereof. In addition, differences in the clinical manifestations of the present case and that of I-EPF are addressed. Because of clinicopathologic similarities between the present case and HIV-associated eosinophilic folliculitis (HIV-EF) in adults, we believe that eosinophilic folliculitis in this patient represents a cutaneous manifestation of HIV infection, rather than co-incidental occurrence of the infantile form of Ofuji's disease in an HIV-positive patient. PMID:10380045

  17. Eosinophilic esophagitis: From pathophysiology to treatment

    PubMed Central

    DAlessandro, Alessandra; Esposito, Dario; Pesce, Marcella; Cuomo, Rosario; De Palma, Giovanni Domenico; Sarnelli, Giovanni

    2015-01-01

    Eosinophilic esophagitis (EoE) is a chronic immune disease, characterized by a dense eosinophilic infiltrate in the esophagus, leading to bolus impaction and reflux-like symptoms. Traditionally considered a pediatric disease, the number of adult patients with EoE is continuously increasing, with a relatively higher incidence in western countries. Dysphagia and food impaction represent the main symptoms complained by patients, but gastroesophageal reflux-like symptoms may also be present. Esophageal biopsies are mandatory for the diagnosis of EoE, though clinical manifestations and proton pump inhibitors responsiveness must be taken into consideration. The higher prevalence of EoE in patients suffering from atopic diseases suggests a common background with allergy, however both the etiology and pathophysiology are not completely understood. Elimination diets are considered the first-line therapy in children, but this approach appears less effective in adults patients, who often require steroids; despite medical treatments, EoE is complicated in some cases by esophageal stricture and stenosis, that require additional endoscopic treatments. This review summarizes the evidence on EoE pathophysiology and illustrates the safety and efficacy of the most recent medical and endoscopic treatments. PMID:26600973

  18. Current Management of Eosinophilic Esophagitis 2015.

    PubMed

    Richter, Joel E

    2016-02-01

    Eosinophilic esophagitis (EoE) is a chronic inflammatory condition characterized by esophageal dysfunction and eosinophilic infiltrate (?15/hpf) in the esophageal epithelium and the absence of other potential causes of eosinophilia. The prevalence is increasing and is the most common cause of solid food dysphagia in children and young adults. This article will review the diagnosis and management of EoE based on consensus conferences, systematic reviews, and meta-analysis and highlights seminal studies in our evolving treatment of this disease. However, all answers are not available and I will remark about the lessons learned in my clinical practice seeing EoE patients over the last 25 years. The complicated etiology of the complaint of dysphagia in EoE patients will be reviewed. The importance of utilizing endoscopy, biopsies, and barium esophagram to help define the 2 phenotypes (inflammatory, fibrostenosis) of EoE will be highlighted. The controversy about PPI-responsive esophageal eosinophilia will be discussed and contrasted with idiopathic EoE. Finally, the 3 treatment options for EoE (drugs, diet, dilation) will be reviewed in detail and a useful clinical management algorithm presented. PMID:26485101

  19. Eosinophilic esophagitis: a bulk of mysteries.

    PubMed

    Straumann, Alex

    2013-01-01

    Eosinophilic esophagitis (EoE), which was first described in the early 1990s, has rapidly evolved as a distinctive chronic inflammatory esophageal disease. The diagnosis is based clinically on the presence of symptoms related to esophageal dysfunction and histologically by an eosinophil-predominant inflammation once other conditions leading to esophageal eosinophilia are excluded. This striking male-prevalent disease has an increasing incidence and prevalence in the Westernized countries. Currently, EoE represents the main cause of dysphagia and bolus impaction in adult patients. Despite the fact that EoE often occurs in atopic patients, the value of allergic testing is still under discussion. Topical corticosteroids lead to a rapid improvement of active EoE clinically and histologically; they are therefore regarded as first-line drug therapy. Elimination diets have similar efficacy as topical corticosteroids, but their long-term use is limited by practical issues. Esophageal dilation of EoE-induced strictures can also be effective in improving symptoms, but this therapy has no effect on the underlying inflammation. Neither the diagnostic nor the long-term therapeutic strategies have been fully defined. Currently, the list of unsolved issues--or mysteries--is still long and a concerted effort on behalf of clinicians and scientists is required to improve the understanding and the therapeutic management of this mysterious disease. PMID:23797116

  20. Association of achalasia and eosinophilic esophagitis.

    PubMed

    Mandaliya, Rohan; DiMarino, Anthony J; Cohen, Sidney

    2013-01-01

    Various esophageal motor disorders including achalasia have been sporadically reported in patients with eosinophilic esophagitis (EoE). The aim of this study was to determine the association between achalasia and EoE and to review the treatment outcomes in patients having both conditions. A retrospective search was conducted to identify the cases of achalasia having EoE over the last 10years at a tertiary care hospital in the United States. Subsequently, a review of the literature was performed to search for cases of achalasia that have concurrent EoE. The retrospective study showed that 4 out of 512 patients of achalasia (<1%) had concomitant EoE. The eosinophil counts were high (80-100/hpf) but the classic endoscopic features of EoE were present in only one patient. Long term outcome following treatment including botox, myotomy and corticosteroids was generally poor. Sixteen patients have been reported in the literature out of which five patients were reported in detail. Patients had good short term response to various therapies. The long term outcomes have not been reported. These studies suggest that a concurrence of these two conditions, although rare, may occur and may not be recognized by usual endoscopic features of EoE. Long term treatment outcomes, distinct from short term in the literature, may be poor. PMID:23054948

  1. Eosinophil Cytokines, Chemokines, and Growth Factors: Emerging Roles in Immunity

    PubMed Central

    Davoine, Francis; Lacy, Paige

    2014-01-01

    Eosinophils derive from the bone marrow and circulate at low levels in the blood in healthy individuals. These granulated cells preferentially leave the circulation and marginate to tissues, where they are implicated in the regulation of innate and adaptive immunity. In diseases such as allergic inflammation, eosinophil numbers escalate markedly in the blood and tissues where inflammatory foci are located. Eosinophils possess a range of immunomodulatory factors that are released upon cell activation, including over 35 cytokines, growth factors, and chemokines. Unlike T and B cells, eosinophils can rapidly release cytokines within minutes in response to stimulation. While some cytokines are stored as pre-formed mediators in crystalloid granules and secretory vesicles, eosinophils are also capable of undergoing de novo synthesis and secretion of these immunological factors. Some of the molecular mechanisms that coordinate the final steps of cytokine secretion are hypothesized to involve binding of membrane fusion complexes comprised of soluble N-ethylmaleimide sensitive factor attachment protein receptors (SNAREs). These intracellular receptors regulate the release of granules and vesicles containing a range of secreted proteins, among which are cytokines and chemokines. Emerging evidence from both human and animal model-based research has suggested an active participation of eosinophils in several physiological/pathological processes such as immunomodulation and tissue remodeling. The observed eosinophil effector functions in health and disease implicate eosinophil cytokine secretion as a fundamental immunoregulatory process. The focus of this review is to describe the cytokines, growth factors, and chemokines that are elaborated by eosinophils, and to illustrate some of the intracellular events leading to the release of eosinophil-derived cytokines. PMID:25426119

  2. Stages of Hairy Cell Leukemia

    MedlinePLUS

    ... Childhood ALL Treatment Childhood AML Treatment Research Hairy Cell Leukemia TreatmentPatient Version (PDQ簧) General Information About Hairy Cell Leukemia Key Points Hairy cell leukemia is a ...

  3. Integrin Activation States and Eosinophil Recruitment in Asthma

    PubMed Central

    Johansson, Mats W.; Mosher, Deane F.

    2013-01-01

    Eosinophil arrest and recruitment to the airway in asthma are mediated, at least in part, by integrins. Eosinophils express 帢4帣1, 帢6帣1, 帢L帣2, 帢M帣2, 帢X帣2, 帢D帣2, and 帢4帣7 integrins, which interact with counter-receptors on other cells or ligands in the extracellular matrix. Whether a given integrin-ligand pair mediates cell adhesion and migration depends on the activation state of the integrin. Integrins exist in an inactive bent, an intermediate-activity extended closed, and a high-activity extended open conformation. Integrin activation states can be monitored by conformation-specific monoclonal antibodies (mAbs). Studies in mice indicate that both 帣1 and 帣2 integrins mediate eosinophil recruitment to the lung. In vitro studies indicate that 帢4帣1 and 帢M帣2 are the principal integrins mediating eosinophil adhesion, including to vascular cell adhesion molecule-1 and the novel 帢M帣2 ligand periostin. In vivo, blood eosinophils have intermediate-activity 帣1 integrins, as judged by mAb N29, apparently resulting from eosinophil binding of P-selectin on the surface of activated platelets, and have a proportion of their 帣2 integrins in the intermediate conformation, as judged by mAb KIM-127, apparently due to exposure to low concentrations of interleukin-5 (IL-5). Airway eosinophils recovered by bronchoalveolar lavage (BAL) after segmental antigen challenge have high-activity 帣1 integrins and high-activity 帢M帣2 that does not require IL-5. Here we review information on how the activation states of eosinophil 帣1 and 帣2 integrins correlate with measurements of eosinophil recruitment and pulmonary function in asthma. Blood eosinophil N29 reactivity is associated with decreased lung function under various circumstances in non-severe asthma and KIM-127 with BAL eosinophil numbers, indicating that intermediate-activity 帢4帣1 and 帢M帣2 of blood eosinophils are important for eosinophil arrest and consequently for recruitment and aspects of asthma. PMID:23554594

  4. 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.

  5. Therapeutic Targeting of Eosinophil Adhesion and Accumulation in Allergic Conjunctivitis

    PubMed Central

    Baiula, Monica; Bedini, Andrea; Carbonari, Gioia; Dattoli, Samantha Deianira; Spampinato, Santi

    2012-01-01

    Considerable evidence indicates that eosinophils are important effectors of ocular allergy. Increased worldwide prevalence of allergic eye pathologies has stimulated the identification of novel drug targets, including eosinophils and adhesion molecules. Accumulation of eosinophils in the eye is a key event in the onset and maintenance of allergic inflammation and is mediated by different adhesion molecules. Antihistamines with multiple mechanisms of action can be effective during the early and late phases of allergic conjunctivitis by blocking the interaction between 帣1 integrins and vascular cell adhesion molecule (VCAM)-1. Small molecule antagonists that target key elements in the process of eosinophil recruitment have been identified and reinforce the validity of 帢4帣1 integrin as a therapeutic target. Glucocorticoids are among the most effective drugs for ocular allergy, but their use is limited by adverse effects. Novel dissociated glucocorticoids can prevent eosinophil accumulation and induce apoptosis of eosinophils, making them promising candidates for ophthalmic drugs. This article reviews recent understanding of the role of adhesion molecules in eosinophil recruitment in the inflamed conjunctiva along with effective treatments for allergic conjunctivitis. PMID:23271999

  6. 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

  7. Diagnostic approach to eosinophilic oesophagitis: Pearls and pitfalls.

    PubMed

    Schoepfer, Alain

    2015-10-01

    Eosinophilic oesophagitis (EoE) has first been described a little over 20 years ago. EoE has been defined by a panel of international experts as a "chronic, immune/antigen-mediated, oesophageal disease, characterized clinically by symptoms related to oesophageal dysfunction and histologically by eosinophil-predominant inflammation". A value of ?15 eosinophils has been defined as histologic diagnostic cutoff. Other conditions associated with oesophageal eosinophilia, such as gastro-oesophageal reflux disease (GERD), PPI-responsive oesophageal eosinophilia, or Crohn's disease should be excluded before EoE can be diagnosed. This review highlights the latest insights regarding the diagnosis and differential diagnosis of EoE. PMID:26552777

  8. Eosinophil granule cationic proteins regulate the classical pathway of complement.

    PubMed Central

    Weiler, J M; Edens, R E; Bell, C S; Gleich, G J

    1995-01-01

    Major basic protein, the primary constituent of eosinophil granules, regulates the alternative and classical pathways of complement. Major basic protein and other eosinophil granule cationic proteins, which are important in mediating tissue damage in allergic disease, regulate the alternative pathway by interfering with C3b interaction with factor B to assemble an alternative pathway C3 convertase. In the present study, eosinophil peroxidase, eosinophil cationic protein and eosinophil-derived neurotoxin, as well as major basic protein, were examined for capacity to regulate the classical pathway. Eosinophil peroxidase, eosinophil cationic protein and major basic protein inhibited formation of cell-bound classical pathway C3 convertase (EAC1,4b,2a), causing 50% inhibition of complement-mediated lysis at about 0.19, 0.75 and 0.5 micrograms/10(7) cellular intermediates, respectively. Eosinophil-derived neurotoxin had no activity on this pathway of complement. The eosinophil granule proteins were examined for activity on the formation of the membrane attack complex. Major basic protein and eosinophil cationic protein had no activity on terminal lysis. In contrast, eosinophil peroxidase inhibited lysis of EAC1,4b,2a,3b,5b, but had only minimal activity on later events in complement lysis. These polycations were then examined to determine the site(s) at which they regulated the early classical pathway. Eosinophil granule polycationic proteins: (1) reduced the Zmax at all time points but had only minimal effect on the Tmax during the formation of the classical pathway C3 convertase (EAC1,4b,2a); (2) inhibited formation of EAC1,4b,2a proportional to C4 but independent of C2 concentration; (3) inhibited fluid phase formation of C1,4b,2a, as reflected by a decrease in C1-induced consumption of C2 over time; and (4) inhibited C1 activity over time without a direct effect on either C4 or C2. These observations suggest that polycations regulate the early classical pathway by interfering with C1 and may exert this activity in vivo. PMID:7750997

  9. Immunohistochemical detection of deposits of eosinophil-derived neurotoxin and eosinophil peroxidase in the myocardium of patients with Chagas' disease.

    PubMed Central

    Molina, H A; Kierszenbaum, F

    1988-01-01

    An immunohistochemical study of eosinophil distribution in the inflammatory cell infiltrates of four different types of myocardial lesions associated with Chagas' disease--caused by Trypanosoma cruzi--showed larger numbers of these cells in areas presenting tissue necrosis and degeneration, most notably in patients with the most severe myocarditis from a histopathological stand-point. Using antisera specific for human eosinophil-derived neurotoxin or eosinophil peroxidase, we detected deposits of these secretion products on myofibres and in the interstitium of chagasic myocardium displaying necrosis and degeneration but rarely in other types of lesions. These deposits were not detectable in the myocardium of non-chagasic patients who had died from myocardial infarction (acute or in the scarring stage) or myocarditis secondary to bacterial endocarditis. When human eosinophil-derived neurotoxin was incubated with myoblast monolayers there was a significant cell injury, detachment and lysis. These effects were abrogated by yeast RNA, added as a competitive ribonuclease substrate, and inhibited by the ribonuclease inhibitor RNasin, suggesting that the ribonuclease activity of the eosinophil-derived neurotoxin was involved in the effect. These results suggest a link between eosinophil infiltration and necrosis in chagasic myocardial lesions and point to EDN, and perhaps other toxic eosinophil secretion products, as possible mediators of tissue damage. Images Figure 1 Figure 2 PMID:3049321

  10. Enhancement of human blood eosinophil cytotoxicity by semi-purified eosinophil colony-stimulating factor(s)

    PubMed Central

    1982-01-01

    Purified human blood eosinophils, when incubated in human placental conditioned medium (a source of colony-stimulating factors) [CSF]) demonstrate an enhanced ability to damage antibody- or complement- coated schistosomula. This enhancement represents a 4- to 10-fold increase of eosinophil schistosomicidal ability and a 10-fold lowering of the threshold for antibody or complement required in the killing reaction. The activity that enhances eosinophil cytotoxicity and the eosinophil colony-stimulating activity in the placental conditioned medium are eluted in the same fraction (CSF-alpha) after chromatography on Sephadex G-100 and phenyl-Sepharose columns, suggesting that these two activities might be associated with the same molecule. CSF-alpha enhances the adherence step of the killing reaction: antibody-coated larvae were frequently found covered by several layers of eosinophils in tubes containing CSF-alpha. Such a degree of adherence was rarely seen in control tubes lacking CSF-alpha. This enhancement of the eosinophil adherence is detectable 45-60 min after addition of CSF- alpha to the culture. It is not affected by washing the cells after a short time of preincubation with CSF-alpha, and it occurs in the absence of protein synthesis, whereas colony-stimulating activity requires continuous protein synthesis and ceases when CSF is removed from the culture. Finally, CSF-alpha enhances the temperature-dependent reaction that insures the irreversibility of eosinophil attachment to schistosomula. These observations suggest that eosinopoietic factors could be responsible for some of the modified properties of blood eosinophils in eosinophilic individuals. PMID:6979609

  11. Genetics Home Reference: Acute promyelocytic leukemia

    MedlinePLUS

    ... leukemia? Acute promyelocytic leukemia is a form of acute myeloid leukemia, a cancer of the blood-forming tissue (bone ... promyelocytic leukemia accounts for about 10 percent of acute myeloid leukemia cases. Acute promyelocytic leukemia occurs in approximately 1 ...

  12. Cellular Mechanisms Underlying Eosinophilic and Neutrophilic Airway Inflammation in Asthma

    PubMed Central

    Vatrella, Alessandro; Busceti, Maria Teresa; Gallelli, Luca; Calabrese, Cecilia; Terracciano, Rosa

    2015-01-01

    Asthma is a phenotypically heterogeneous chronic disease of the airways, characterized by either predominant eosinophilic or neutrophilic, or even mixed eosinophilic/neutrophilic inflammatory patterns. Eosinophilic inflammation can be associated with the whole spectrum of asthma severity, ranging from mild-to-moderate to severe uncontrolled disease, whereas neutrophilic inflammation occurs mostly in more severe asthma. Eosinophilic asthma includes either allergic or nonallergic phenotypes underlying immune responses mediated by T helper (Th)2 cell-derived cytokines, whilst neutrophilic asthma is mostly dependent on Th17 cell-induced mechanisms. These immune-inflammatory profiles develop as a consequence of a functional impairment of T regulatory (Treg) lymphocytes, which promotes the activation of dendritic cells directing the differentiation of distinct Th cell subsets. The recent advances in the knowledge of the cellular and molecular mechanisms underlying asthmatic inflammation are contributing to the identification of novel therapeutic targets, potentially suitable for the implementation of future improvements in antiasthma pharmacologic treatments. PMID:25878402

  13. Diagnosis and management of eosinophilic asthma: a US perspective

    PubMed Central

    Walford, Hannah H; Doherty, Taylor A

    2014-01-01

    Eosinophilic asthma is now recognized as an important subphenotype of asthma based on the pattern of inflammatory cellular infiltrate in the airway. Eosinophilic asthma can be associated with increased asthma severity, atopy, late-onset disease, and steroid refractoriness. Induced sputum cell count is the gold standard for identifying eosinophilic inflammation in asthma although several noninvasive biomarkers, including fractional exhaled nitric oxide and periostin, are emerging as potential surrogates. As novel therapies and biologic agents become increasingly available, there is an increased need for specific phenotype-directed treatment strategies. Greater recognition and understanding of the unique immunopathology of this asthma phenotype has important implications for management of the disease and the potential to improve patient outcomes. The present review provides a summary of the clinical features, pathogenesis, diagnosis, and management of eosinophilic asthma. PMID:24748808

  14. UNUSUAL EOSINOPHILIC GRANULE CELL PROLIFERATION IN COHO SALMON (ONCHORHYNCHUS KISUTCH)

    EPA Science Inventory

    Proliferative lesions comprised of eosinophilic granule cells (EGCs) extended throughout the gastrointestinal tract of several mature, spawning coho salmon Oncorhynchus kisutch (Walbaum). istological examination of the tumour showed extensive proliferation and infiltration of EGC...

  15. [Eosinophilic gastroenteritis and colitis in pediatric patients: Increasingly frequent diseases].

    PubMed

    Lemale, J; Dainese, L; Tounian, P

    2015-07-01

    Eosinophilic gastrointestinal disorders are a heterogeneous group of disorders characterized by no specific digestive symptoms associated with dense eosinophilic inflammation of the gastrointestinal tract in the absence of known causes for such tissue eosinophilia. Among these diseases, eosinophilic gastroenteritis (EGE) and colitis (EC) are less common than esophagitis, but their incidence and prevalence have been increasing over the past decade due in part to increased disease recognition. The exact pathophysiology is not clear: EGE and EC are immune-mediated diseases implicating adaptive T-helper cell type 2 immunity. According to the site of eosinophilic infiltration, there is a wide spectrum of digestive symptoms ranging from food refusal, nausea, vomiting, abdominal pain, weight loss, gastrointestinal bleeding (anemia), protein loosing enteropathy, ascites, bowel obstruction or perforation for EGE and diarrhea 簣 bleeding for CE. Endoscopic lesions are not specific: friability, erythematous mucosa with superficial erosions, or ulceration is often observed. Histologically, markedly increased numbers of mucosal eosinophils are seen in biopsy specimens. However, no standards for the diagnosis of EGE or CE exist and few findings support the diagnosis: intraepithelial eosinophils, eosinophil crypt abscesses, and eosinophils in muscularis mucosa and/or submucosa. Other organs are not involved. The other causes of tissue eosinophilia (infections, inflammatory bowel diseases) should be excluded. Food allergy appears to play a central role in driving inflammation in EGE and CE, as evidenced by symptomatic improvement with initiation of food exclusion or elemental diets. Dietary treatment should be the first therapeutic option in children. If the elimination diet fails, corticosteroids are currently the best characterized treatment but appropriate duration is unknown and relapses are frequent. In severe forms, immunomodulators or biologic agents (anti-IL5, anti-IgE, or anti-TNFa) can potentially play a role in the treatment of EGE and CE. PMID:26051270

  16. Role of tissue eosinophils in oral Leukoplakia: A pilot study

    PubMed Central

    Madhura, MG; Gajalakshmi, S; Kumar, B Veerendra; Suma, S; Sarita, Y; Shweta, RD

    2015-01-01

    Context: Tissue eosinophilia in oral squamous cell carcinoma has been well - recognized. Studies have reported both favorable and unfavorable prognoses associated with tissue eosinophils in oral squamous cell carcinoma. However, the role of eosinophils in the development of tumor is still unclear. Aims: The present study was an attempt to elucidate the potential role of tissue eosinophils in oral leukoplakia, a potentially malignant lesion. Settings and Design: To count eosinophils in tissues of normal subjects and oral leukoplakia cases. To compare tissue eosinophil count (TEC) between normal and oral leukoplakia cases. To compare TEC between dysplastic and non-dysplastic cases of oral leukoplakia and to correlate with degree of epithelial dysplasia. Materials and Methods: A total of 85 cases (59 cases of oral leukoplakia and 26 normal oral tissues) constituted the study material. Tissue eosinophils were counted in 10 different high- power fields. Statistical Analysis Used: Non-parametric tests (Mann-Whitney U-test, Kruskal-Wallis test, Mann-Whitney post hoc analysis and Spearman's correlation statistics). Results: Mean eosinophil count (MEC) in oral leukoplakia cases was significantly more when compared to normal subjects. MEC in dysplastic cases of oral leukoplakia was significantly more when compared to those without epithelial dysplasia (Mann-Whitney U-test). Furthermore, MEC was directly proportional to the degree of epithelial dysplasia (Spearman's correlation statistics). Conclusions: TEC may be used as an adjunct to predict the malignant transformation of dysplastic cases of oral leukoplakia. Eosinophilic infiltration in oral dysplastic cases should prompt a thorough evaluation for invasiveness, especially when features of invasion are absent or suspected in smaller biopsy specimens. Use of TEC as a prognostic indicator demands larger sample size and mandates long-term follow-up. PMID:26980954

  17. Bactericidal Activity of Human Eosinophilic Granulocytes against Escherichia coli

    PubMed Central

    Persson, Terese; Andersson, Pia; Bodelsson, Mikael; Laurell, Martin; Malm, Johan; Egesten, Arne

    2001-01-01

    Eosinophils participate in allergic inflammation and may have roles in the body's defense against helminthic infestation. Even under noninflammatory conditions, eosinophils are present in the mucosa of the large intestine, where large numbers of gram-negative bacteria reside. Therefore, roles for eosinophils in host defenses against bacterial invasion are possible. In a system for bacterial viable counts, the bactericidal activity of eosinophils and the contribution of different cellular antibacterial systems against Escherichia coli were investigated. Eosinophils showed a rapid and efficient killing of E. coli under aerobic conditions, whereas under anaerobic conditions bacterial killing decreased dramatically. In addition, diphenylene iodonium chloride (DPI), an inhibitor of the NADPH oxidase and thereby of superoxide production, also significantly inhibited bacterial killing. The inhibitor of nitric oxide (NO) production l-N5-(1-iminoethyl)-ornithine dihydrochloride did not affect the killing efficiency, suggesting that NO or derivatives thereof are of minor importance under the experimental conditions used. To investigate the involvement of superoxide and eosinophil peroxidase (EPO) in bacterial killing, EPO was blocked by azide. The rate of E. coli killing decreased significantly in the presence of azide, whereas addition of DPI did not further decrease the killing, suggesting that superoxide acts in conjunction with EPO. Bactericidal activity was seen in eosinophil extracts containing granule proteins, indicating that oxygen-independent killing may be of importance as well. The findings suggest that eosinophils can participate in host defense against gram-negative bacterial invasion and that oxygen-dependent killing, i.e., superoxide acting in conjunction with EPO, may be the most important bactericidal effector function of these cells. PMID:11349018

  18. Eosinophil-derived IL-10 supports chronic nematode infection1

    PubMed Central

    Huang, Lu; Gebreselassie, Nebiat G.; Gagliardo, Lucille F.; Ruyechan, Maura C.; Lee, Nancy A.; Lee, James J.; Appleton, Judith A.

    2014-01-01

    Eosinophilia is a feature of the host immune response that distinguishes parasitic worms from other pathogens, yet a discrete function for eosinophils in worm infection has been elusive. The aim of this study was to clarify the mechanism(s) underlying the striking and unexpected observation that eosinophils protect intracellular, muscle-stage Trichinella spiralis larvae against NO-mediated killing. Our findings indicate that eosinophils are specifically recruited to sites of infection at the earliest stage of muscle infection, consistent with a local response to injury. Early recruitment is essential for larval survival. By producing IL-10 at the initiation of infection, eosinophils expand IL-10+ myeloid dendritic cells and CD4+ IL-10+ T lymphocytes that inhibit iNOS expression and protect intracellular larvae. The results document a novel immunoregulatory function of eosinophils in helminth infection, in which eosinophil-derived IL-10 drives immune responses that eventually limit local nitric oxide production. In this way, the parasite co-opts an immune response in a way that enhances its own survival. PMID:25210122

  19. Eosinophilic ascites: A case report and literature review.

    PubMed

    Alsulaiman, Raed M

    2015-01-01

    Eosinophilic gastroenteritis is a rare gastrointestinal (GI) disorder characterized by nonspecific GI symptoms, peripheral eosinophilia, and eosinophilic infiltration of the intestinal wall. The disorder is classified into mucosal, muscular, and sub-serosal types, depending on the clinical picture and the depth of eosinophilic infiltration within the GI wall. Sub-serosal disease, which is complicated by ascites, usually results in the most severe clinical form of eosinophilic gastroenteritis and requires early corticosteroid therapy. In such cases, a favorable outcome can be achieved after a short course of corticosteroids. We present the case of a 28-year-old female with diffuse abdominal pain and distention for 2 weeks. Her physical examination was significant for moderate ascites. Initial work-up demonstrated severe peripheral blood eosinophilia, normal liver function tests, and elevated serum immunoglobulin E (IgE). Upper endoscopy, colonoscopy showed a thickening of the stomach and colon, and biopsies showed marked eosinophilic infiltration of the mucosa. Ascitic fluid analysis showed significant eosinophilia. Subsequent treatment with oral prednisone resulted in the normalization of laboratory and radiologic abnormalities 45 days after the start of the treatment. Despite its rarity, eosinophilic gastroenteritis needs to be recognized by the clinician because the disease is treatable, and timely diagnosis and initiation of treatment could be of major importance. PMID:26392801

  20. Inhibitory action of quercetin on eosinophil activation in vitro.

    PubMed

    Sakai-Kashiwabara, Misako; Asano, Kazuhito

    2013-01-01

    The influence of quercetin on eosinophil functions was examined in vitro and in vivo. The first set of experiments was undertaken to examine whether quercetin could suppress eosinophilia and IgE hyperproduction induced by Mesocestoides corti infection in BALB/c mice. The number of peripheral blood eosinophils and IgE levels were examined 21 days after infection. Oral administration of quercetin for 21 days could not suppress both peripheral blood eosinophilia and IgE hyperproduction, even when 20.0mg/kg quercetin was used for treatment. The second part of the experiment was designed to examine the influence of quercetin on eosinophil activation induced by SCF stimulation in vitro. Eosinophils were obtained from M. corti-infected mice and stimulated with SCF in the presence of various concentrations of quercetin for 24h. The addition of quercetin into cell cultures could suppress eosinophil activation induced by SCF stimulation as assessed by measuring the contents of RANTES, MIP-1 帣 , ECP, and MBP in culture supernatants. The minimum concentration of quercetin which caused significant suppression of factor secretion was 5.0 弮 M. These results may suggest that quercetin will be a good candidate for the supplement on the management of eosinophil-mediated diseases, such as allergic rhinitis and asthma. PMID:23840245

  1. Clinical application of autologous technetium-99m-labelled eosinophils to detect focal eosinophilic inflammation in the lung.

    PubMed

    Loutsios, Chrystalla; Farahi, Neda; Simmonds, Rosalind; Cullum, Ian; Gillett, Daniel; Solanki, Chandra; Solanki, Kishor; Buscombe, John; Condliffe, Alison M; Peters, A Mike; Chilvers, Edwin R

    2015-11-01

    The detection of focal eosinophilic inflammation by non-invasive means may aid the diagnosis and follow-up of a variety of pulmonary pathologies. All current methods of detection involve invasive sampling, which may be contraindicated or too high-risk to be performed safely. The use of injected autologous technetium-99m (Tc-99m)-labelled eosinophils coupled to single-photon emission computed tomography (SPECT) has been demonstrated to localise eosinophilic inflammation in the lungs of a patient with antineutrophil cytoplasmic antibody-positive vasculitis. Here, we report on the utility of this technique to detect active eosinophilic inflammation in a patient with focal lung inflammation where a biopsy was contraindicated. PMID:26108571

  2. Acute Lymphocytic Leukemia

    MedlinePLUS

    ... hard for blood to do its work. In acute lymphocytic leukemia (ALL), also called acute lymphoblastic leukemia, there are too ... of white blood cells called lymphocytes or lymphoblasts. ALL is the most common type of cancer in ...

  3. 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. ...

  4. 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 ...

  5. RECOGNITION OF FUNGAL PROTEASE ACTIVITIES INDUCES CELLULAR ACTIVATION AND EOSINOPHIL-DERIVED NEUROTOXIN RELEASE IN HUMAN EOSINOPHILS1

    PubMed Central

    Matsuwaki, Yoshinori; Wada, Kota; White, Thomas A.; Benson, Linda M.; Charlesworth, M. Cristine; Checkel, James L.; Inoue, Yoshinari; Hotta, Kyoko; Ponikau, Jens U; Lawrence, Christopher B.; Kita, Hirohito

    2010-01-01

    Eosinophils are multifunctional leukocytes implicated in the pathogenesis of asthma and in immunity to certain organisms. Associations between exposure to an environmental fungus, such as Alternaria, and asthma have been recognized clinically. Protease-activated receptors (PARs) are G protein-coupled receptors that are cleaved and activated by serine proteases, but their roles in innate immunity remain unknown. We previously found that human eosinophils respond vigorously to Alternaria organisms and to the secretory product(s) of Alternaria with eosinophils releasing their pro-inflammatory mediators. Herein, we investigated the roles of protease(s) produced by Alternaria and of PARs expressed on eosinophils in their immune responses against fungal organisms. We found that Alternaria alternata produces aspartate protease(s) and that human peripheral blood eosinophils degranulate in response to the cell-free extract of A. alternata. Eosinophils showed an increased intracellular calcium concentration ([Ca2+]i) in response to Alternaria that was desensitized by peptide and protease ligands for PAR-2 and inhibited by a PAR-2 antagonistic peptide. Alternaria-derived aspartate protease(s) cleaved PAR-2 to expose neo-ligands; these neo-ligands activated eosinophil degranulation in the absence of proteases. Finally, treatment of Alternaria extract with aspartate protease inhibitors, which are conventionally used for HIV-1 and other microbes, attenuated the eosinophils responses to Alternaria. Thus, fungal aspartate protease and eosinophil PAR-2 appear critical for the eosinophils innate immune response to certain fungi, suggesting a novel mechanism for pathologic inflammation in asthma and for host-pathogen interaction. PMID:19864598

  6. Human vs. Mouse Eosinophils: That which we call an eosinophil, by any other name would stain as red

    PubMed Central

    Lee, James J.; Jacobsen, Elizabeth A.; Ochkur, Sergei I; McGarry, Michael P.; Condjella, Rachel M.; Doyle, Alfred D.; Luo, Huijun; Zellner, Katie R.; Protheroe, Cheryl A.; Willetts, Lian; LeSuer, William E.; Colbert, Dana C.; Helmers, Richard A.; Lacy, Paige; Moqbel, Redwan; Lee, Nancy A.

    2012-01-01

    The respective life histories of humans and mice are well defined and describe a unique story of evolutionary conservation extending from sequence identity within the genome to the underpinnings of biochemical, cellular, and physiological pathways. As a consequence, the hematopoietic lineages of both species are invariantly maintained, each with identifiable eosinophils. This canonical presence nonetheless does not preclude disparities between human and mouse eosinophils and/or their effector functions. Indeed, many books and reviews dogmatically highlight differences, providing a rationale to discount the use of mouse models of human eosinophilic diseases. We suggest that this perspective is parochial and ignores the wealth of available studies and the consensus of the literature that overwhelming similarities (and not differences) exist between human and mouse eosinophils. The goal of this review is to summarize this literature and in some cases provide the experimental details, comparing and contrasting eosinophils and eosinophil effector functions in humans vs. mice. In particular, our review will provide a summation and an easy to use reference guide to important studies demonstrating that while differences exist, more often than not their consequences are unknown and do not necessarily reflect inherent disparities in eosinophil function, but instead, species-specific variations. The conclusion from this overview is that despite nominal differences, the vast similarities between human and mouse eosinophils provide important insights as to their roles in health and disease and, in turn, demonstrate the unique utility of mouse-based studies with an expectation of valid extrapolation to the understanding and treatment of patients. PMID:22935586

  7. Tribbles in acute leukemia.

    PubMed

    Liang, Kai Ling; Rishi, Loveena; Keeshan, Karen

    2013-05-23

    There is growing research interest in the mammalian Tribbles (Trib) family of serine/threonine pseudokinases and their oncogenic association with acute leukemias. This review is to understand the role of Trib genes in hematopoietic malignancies and their potential as targets for novel therapeutic strategies in acute myeloid leukemia and acute lymphoblastic leukemia. We discuss the role of Tribs as central signaling mediators in different subtypes of acute leukemia and propose that inhibition of dysregulated Trib signaling may be therapeutically beneficial. PMID:23550039

  8. An essential role for Rab27a GTPase in eosinophil exocytosis

    PubMed Central

    Kim, John Dongil; Willetts, Lian; Ochkur, Sergei; Srivastava, Nutan; Hamburg, Rudolf; Shayeganpour, Anooshirvan; Seabra, Miguel C.; Lee, James J.; Moqbel, Redwan; Lacy, Paige

    2013-01-01

    Eosinophil degranulation has been implicated in inflammatory processes associated with allergic asthma. Rab27a, a Rab-related GTPase, is a regulatory intracellular signaling molecule expressed in human eosinophils. We postulated that Rab27a regulates eosinophil degranulation. We investigated the role of Rab27a in eosinophil degranulation within the context of airway inflammation. Rab27a expression and localization in eosinophils were investigated by using subcellular fractionation combined with Western blot analysis, and the results were confirmed by immunofluorescence analysis of Rab27a and the granule membrane marker CD63. To determine the function of eosinophil Rab27a, we used Ashen mice, a strain of Rab27a-deficient animals. Ashen eosinophils were tested for degranulation in response to PAF and calcium ionophore by measuring released EPX activity. Airway EPX release was also determined by intratracheal injection of eosinophils into mice lacking EPX. Rab27a immunoreactivity colocalized with eosinophil crystalloid granules, as determined by subcellular fractionation and immunofluorescence analysis. PAF induced eosinophil degranulation in correlation with redistribution of Rab27a+ structures, some of which colocalized with CD63+ crystalloid granules at the cell membrane. Eosinophils from mice had significantly reduced EPX release compared with normal WT eosinophils, both in vitro and in vivo. In mouse models, Ashen mice demonstrated reduced EPX release in BAL fluid. These findings suggest that Rab27a has a key role in eosinophil degranulation. Furthermore, these findings have implications for Rab27a-dependent eosinophil degranulation in airway inflammation. PMID:23986549

  9. An essential role for Rab27a GTPase in eosinophil exocytosis.

    PubMed

    Kim, John Dongil; Willetts, Lian; Ochkur, Sergei; Srivastava, Nutan; Hamburg, Rudolf; Shayeganpour, Anooshirvan; Seabra, Miguel C; Lee, James J; Moqbel, Redwan; Lacy, Paige

    2013-12-01

    Eosinophil degranulation has been implicated in inflammatory processes associated with allergic asthma. Rab27a, a Rab-related GTPase, is a regulatory intracellular signaling molecule expressed in human eosinophils. We postulated that Rab27a regulates eosinophil degranulation. We investigated the role of Rab27a in eosinophil degranulation within the context of airway inflammation. Rab27a expression and localization in eosinophils were investigated by using subcellular fractionation combined with Western blot analysis, and the results were confirmed by immunofluorescence analysis of Rab27a and the granule membrane marker CD63. To determine the function of eosinophil Rab27a, we used Ashen mice, a strain of Rab27a-deficient animals. Ashen eosinophils were tested for degranulation in response to PAF and calcium ionophore by measuring released EPX activity. Airway EPX release was also determined by intratracheal injection of eosinophils into mice lacking EPX. Rab27a immunoreactivity colocalized with eosinophil crystalloid granules, as determined by subcellular fractionation and immunofluorescence analysis. PAF induced eosinophil degranulation in correlation with redistribution of Rab27a(+) structures, some of which colocalized with CD63(+) crystalloid granules at the cell membrane. Eosinophils from mice had significantly reduced EPX release compared with normal WT eosinophils, both in vitro and in vivo. In mouse models, Ashen mice demonstrated reduced EPX release in BAL fluid. These findings suggest that Rab27a has a key role in eosinophil degranulation. Furthermore, these findings have implications for Rab27a-dependent eosinophil degranulation in airway inflammation. PMID:23986549

  10. An overview of chronic myeloid leukemia and its animal models.

    PubMed

    Ma, WeiXu; Ma, Ning; Chen, XiaoHui; Zhang, YiYue; Zhang, WenQing

    2015-12-01

    Chronic myeloid leukemia (CML) is a form of leukemia characterized by the presence of clonal bone marrow stem cells with the proliferation of mature granulocytes (neutrophils, eosinophils, and basophils) and their precursors. CML is a type of myeloproliferative disease associated with a characteristic chromosomal translocation called the Philadelphia (Ph) chromosome or t (9;22) translocation (BCR-ABL). CML is now usually treated with targeted drugs called tyrosine kinase inhibitors (TKIs). The mechanism and natural history of CML is still unclear. Here, we summarize the present CML animal disease models and compare them with each other. Meanwhile, we propose that it is a very wise choice to establish zebrafish (Danio rerio) CML model mimics clinical CML. This model could be used to learn more about the mechanism of CML, and to aid in the development of new drugs to treat CML. PMID:26582013

  11. IL-33 enhances Siglec-8 mediated apoptosis of human eosinophils

    PubMed Central

    Na, Ho Jeong; Hudson, Sherry A.; Bochner, Bruce S.

    2012-01-01

    IL-33 activates eosinophils directly via the ST2 receptor. Like IL-5, IL-33 induces eosinophilia and eosinophilic airway inflammation in mouse models and primes human eosinophil responses. Previously, we reported that IL-5 priming enhances Siglec-8 mediated mitochondrial and reactive oxygen species (ROS)-dependent eosinophilic apoptosis and eliminates caspase dependence of this cell death process. Whether IL-33, like IL-5, augments pro-apoptotic pathways involving receptors such as Siglec-8 and in a similar manner has not been explored. Annexin-V labeling was performed to detect apoptosis in human eosinophils pre-incubated with or without a range of concentrations of IL-33 and/or IL-5 in the presence or absence of Siglec-8 monoclonal antibody (mAb) 2C4 and inhibitors of caspases. Tetramethyl-rhoda-mine staining was used as a marker of mitochondrial membrane potential loss and injury. ROS production was determined by measuring the superoxide dismutase-inhibitable reduction of cytochrome c. Cleavage of poly(ADP-ribose) polymerase (PARP) was assessed using Western blotting. Eosinophils cultured alone or with mAb 2C4 underwent low levels of apoptosis at 24 h. 2C4-induced eosinophil apoptosis was markedly and equally enhanced after culture for 24 h with either IL-33 or IL-5, although IL-5 was more potent. Effects on apoptosis with IL-33 and IL-5 were synergistic. In contrast, percentages of cells exhibiting reduced mitochondrial membrane potential were greater with IL-33 than IL-5 and effects of these cytokines were also synergistic. Antimycin, an inhibitor of mitochondrial electron transport, almost completely inhibited 2C4-induced apoptosis with either IL-33 or IL-5. Surprisingly, 2C4-induced eosinophil ROS production was significantly enhanced with IL-5 but not IL-33. Siglec-8-mediated apoptosis in the presence of IL-33 was more sensitive in magnitude than IL-5 to inhibition by the pan-caspase inhibitor Z-VAD-FMK, yet both cytokine conditions were associated with PARP cleavage. These data demonstrate that IL-33 is as effective but less potent than IL-5 in enhancing Siglec-8-mediated eosinophil apoptosis, and can synergize with IL-5. Eosinophils primed by IL-33 and/or IL-5 in vivo would be expected to display enhanced susceptibility to undergoing Siglec-8-induced apoptosis. PMID:22079334

  12. Acute Myeloid Leukemia

    Cancer.gov

    Acute myeloid leukemia (AML) is a cancer of the blood and bone marrow. An acute leukemia can become worse quickly if it is not treated and can result in death within months. AML is the most common type of acute leukemia in American adults and the average age of a patient with AML is 67.

  13. Clinical and radiological character of eosinophilic cystitis

    PubMed Central

    Li, Gang; Cai, Bing; Song, Hualin; Yang, Zhi

    2015-01-01

    Purpose: Eosinophilic cystitis (EC) is a rare disease and remains a poorly understood. We explored the potential etiology, clinical and radiological presentation, diagnosis and therapeutic experience with EC. Materials and Methods: A pooled ten patients diagnosed with EC were retrospectively studied in our hospital to assess clinical presentation symptoms, radiological and pathological diagnosis, treatment and outcomes between 1998 and 2012. Results: Nine patients presented with irritative urinary symptoms, one was symptomless. Allergic history were found in 2 patients, bladder mass was detected in all by radiologic tests or cystoscopy. Radiology revealed diffuse thickening of bladder wall in 7 cases among which one with bilateral hydroureteronephrosis, solitary tumor-like lesion in other 3. Elevated serum leukocytes were evident in 4 cases while elevated peripheral eosinophilias were observed in 3. One was asymptomatic and without specific therapy (group 1, 10%), transurethral resection of the lesions in one tumor-like case (10%). The other 8 cases were treated with corticosteroid and/or antihistaminics and 5 patients had excellent outcome with symptom resolution (62.5%). Conclusions: EC usually follows a benign course, most treated with corticosteroids and resulted in relief of symptoms while some may relapse. Surgery is an available choice for drug refractory or localized EC. PMID:25785027

  14. Diagnosis and classification of eosinophilic fasciitis.

    PubMed

    Pinal-Fernandez, I; Selva-O' Callaghan, A; Grau, J M

    2014-01-01

    Eosinophilic fasciitis (EF) is a rare scleroderma-like syndrome with an unknown etiology and pathogenesis that should be considered an immune-allergic disorder. Painful swelling with progressive induration and thickening of the skin and soft tissues of the limbs and trunk are the clinical hallmarks of the disease. Peripheral blood eosinophilia, hypergammaglobulinemia, and elevated erythrocyte sedimentation rate are the main laboratory findings. Full-thickness wedge biopsy of the clinically affected skin showing inflammation and thickening of deep fascia is essential to establish the diagnosis. The differential diagnosis includes systemic sclerosis and other scleroderma subsets such as morphea, and epidemic fasciitis syndromes caused by toxic agents such as the myalgia-eosinophilia syndrome and toxic oil syndrome. Peripheral T cell lymphomas should also be ruled out. The diagnosis of EF can be established by clinical, laboratory and histological findings, but universally accepted international diagnostic criteria are lacking. Corticosteroids are efficacious and remain the standard therapy for EF, although some patients may improve spontaneously. PMID:24424187

  15. Clavicular eosinophilic granuloma causing adult shoulder pain.

    PubMed

    Sugi, Michelle T; Fedenko, Alexander N; Menendez, Lawrence R; Allison, Daniel C

    2013-02-11

    Though rarely reported, neoplasms of the clavicle occur, and their symptoms can be mistaken for more common shoulder conditions. We present the case of a benign clavicular neoplasm, rarely seen in adults, presenting with pain, and eventual pathologic fracture in a 49 year-old. A 49 year-old male firefighter underwent arthroscopic rotator cuff repair for shoulder pain after magnetic resonance imaging revealed supraspinatus tendon tear. The patient's pain persisted after surgery, and was described as routine until he developed severe pain after minor blunt trauma. A local Emergency Room performed the first x-rays, which revealed a pathologic fracture of the distal clavicle through a destructive lesion. The patient was referred to an orthopedic oncologist, who performed incisional biopsy, which initially diagnosed osteomyelitis. The patient was subsequently taken to surgery for debridement. Pathology then yielded the diagnosis of eosinophilic granuloma. The patient was taken back to surgery for formal curettage with open reduction and internal fixation. The patient's pain resolved, the pathologic fracture fully healed, and the patient returned to full time work as a firefighter. Though workup for common shoulder conditions often identifies incidental benign lesions of bone, the converse can be true. Persistent pain despite intervention should raise concern for further investigation. An x-ray alone can reveal a destructive bone lesion as the source of shoulder pain. PMID:23772307

  16. Eosinophils and mast cells in leishmaniasis.

    PubMed

    Rodr穩guez, Nilda E; Wilson, Mary E

    2014-08-01

    Leishmania spp. are parasitic protozoa endemic in tropical and subtropical regions and the causative agent of leishmaniasis, a collection of syndromes whose clinical manifestations vary according to host and pathogen factors. Leishmania spp. are inoculated into the mammalian host by the bite of an infected sand fly, whereupon they are taken up by phagocytosis, convert into the replicative amastigote stage within macrophages, reproduce, spread to new macrophages and cause disease manifestations. A curative response against leishmaniasis depends in the classical activation of macrophages and the IL-12-dependent onset of an adaptive type 1 response characterized by the production of IFN-帠. Emerging evidence suggests that neutrophils, dendritic cells and other immune cells can serve as either temporary or stable hosts for Leishmania spp. Furthermore, it is becoming apparent that the initial interactions of the parasite with resident or early recruited immune cells can shape both the macrophage response and the type of adaptive immune response being induced. In this review, we compile a growing number of studies demonstrating how the earliest interactions of Leishmania spp. with eosinophils and mast cells influence the macrophage response to infection and the development of the adaptive immune response, hence, determining the ultimate outcome of infection. PMID:24838146

  17. Leukemia stem cells.

    PubMed

    Testa, Ugo

    2011-03-01

    Leukemia-initiating cells (LICs) or leukemia stem cells (LSCs) are defined by their ability to form tumors after xenotransplantation in immunodeficient mice and appear to be rare in most human leukemias. In various leukemias, only small subpopulations of cells can transfer disease upon transplantation into immunocompromised NOD/SCID mice, and markers that distinguish the leukemogenic cancer cells from the bulk populations of non-leukemogenic cells have been identified. However, the phenotype of LICs is heterogeneous: it is variable for the different types of acute myeloid leukemias; cells with different membrane phenotype can act as LICs in each B-acute lymphoid leukemia; LICs change during the evolution of chronic myeloid leukemia from the chronic to the acute phase. There is a general consensus that the identification and characterization of leukemic stem cells might lead to the identification of new therapeutic targets and, through this way, to more effective treatments by focusing therapy on the most malignant cells. PMID:21107841

  18. Modulation of human eosinophil polymorphonuclear leukocyte migration and function.

    PubMed Central

    Goetzl, E. J.

    1976-01-01

    Eosinophil migration toward a concentration gradient of a chemotactic factor is regulated at four levels. Diverse immunologic pathways generate stimuli with eosinophil chemotactic activity, including the complement products C5a and a fragment of C3a and the peptide products of mast cells and basophils activated by IgE-mediated reactions, such as eosinophil chemotactic factor of anaphylaxis (ECF-A) and other oligopeptides. The intrinsic preferential leukocyte activity of the chemotactic stimuli represents the second level of modulation, with ECF-A and other mast cell-derived peptides exhibiting the most selective action on eosinophils. The third level of control of eosinophil chemotaxis is composed of inactivators and inhibitors of chemotactic stimuli and is exemplified by degradation of C5a by anaphylatoxin inactivator or chemotactic factor inactivator and of ECF-A by carboxypeptidase-A or aminopeptidases. The activity of ECF-A is uniquely suppressed by equimolar quantities of its NH2- terminal tripeptide substituent, presumably by eosinophil membrane receptor competition. Factors comprising the fourth level of regulation, which alter eosinophil responsiveness to chemotactic stimuli, include the chemotactic factors themselves, through deactivation; nonchemotactic inhibitors such as the COOH-terminal tripeptide substituent of ECF-A, the neutrophil-immobilizing factor (NIF), the phagocytosis-enhancing factor Thr-Lys-Pro-Arg, and histamine at concentrations greater than 400 ng/ml; and nonchemotactic enhancing principles represented by ascorbate and by histamine at concentrations of 30 ng/ml or less. Local concentrations of eosinophils called to and immobilized at the site of a hypersenitivity reaction may express their regulatory functions by degrading the chemical mediators elaborated including histamine, slow-reacting substance of anaphylaxis (SRS-A), and platelet-activating factor (PAF) by way of their content of histaminase, arylsulfatase B, and phospholipase D, respectively. Immunologic pathways may thus provide the capability for early and specific host defense reactions with a later influx of eosinophils preventing irreversible local tissue alterations or distant organ effects. PMID:793410

  19. Does eosinophilic COPD exacerbation have a better patient outcome than non-eosinophilic in the intensive care unit?

    PubMed Central

    Saltrk, Cneyt; Karakurt, Zuhal; Adiguzel, Nalan; Kargin, Feyza; Sari, Rabia; Celik, M Emin; Takir, Huriye Berk; Tuncay, Eylem; Sogukpinar, Ozlem; Ciftaslan, Nezihe; Mocin, Ozlem; Gungor, Gokay; Oztas, Selahattin

    2015-01-01

    Background COPD exacerbations requiring intensive care unit (ICU) admission have a major impact on morbidity and mortality. Only 10%25% of COPD exacerbations are eosinophilic. Aim To assess whether eosinophilic COPD exacerbations have better outcomes than non-eosinophilic COPD exacerbations in the ICU. Methods This retrospective observational cohort study was conducted in a thoracic, surgery-level III respiratory ICU of a tertiary teaching hospital for chest diseases from 2013 to 2014. Subjects previously diagnosed with COPD and who were admitted to the ICU with acute respiratory failure were included. Data were collected electronically from the hospital database. Subjects characteristics, complete blood count parameters, neutrophil to lymphocyte ratio (NLR), delta NLR (admission minus discharge), C-reactive protein (CRP) on admission to and discharge from ICU, length of ICU stay, and mortality were recorded. COPD subjects were grouped according to eosinophil levels (>2% or ?2%) (group 1, eosinophilic; group 2, non-eosinophilic). These groups were compared with the recorded data. Results Over the study period, 647 eligible COPD subjects were enrolled (62 [40.3% female] in group 1 and 585 [33.5% female] in group 2). Group 2 had significantly higher C-reactive protein, neutrophils, NLR, delta NLR, and hemoglobin, but a lower lymphocyte, monocyte, and platelet count than group 1, on admission to and discharge from the ICU. Median (interquartile range) length of ICU stay and mortality in the ICU in groups 1 and 2 were 4 days (27 days) vs 6 days (39 days) (P<0.002), and 12.9% vs 24.9% (P<0.034), respectively. Conclusion COPD exacerbations with acute respiratory failure requiring ICU admission had a better outcome with a peripheral eosinophil level >2%. NLR and peripheral eosinophilia may be helpful indicators for steroid and antibiotic management. PMID:26392758

  20. Advances in Clinical Management of Eosinophilic Esophagitis

    PubMed Central

    Dellon, Evan S.; Liacouras, Chris A.

    2014-01-01

    EoE is a chronic immune/antigen-mediated clinicopathologic condition that has become an increasingly important cause of upper gastrointestinal morbidity in adults and children over the past 2 decades. It is diagnosed based on symptoms of esophageal dysfunction, the presence of at least 15 eosinophils/high-power field in esophageal biopsies, and exclusion of competing causes of esophageal eosinophilia, including proton pump inhibitor-responsive esophageal eosinophilia (PPI-REE). We review what we have recently learned about the clinical aspects of EoE, discussing the clinical, endoscopic, and histologic features of EoE in adults and children. We explain the current diagnostic criteria and challenges to diagnosis, including the role of gastroesophageal reflux disease and PPI-REE. It is also important to consider the epidemiology of EoE (current incidence of 1/10,000 new cases per year and prevalence of 0.5-1/1,000 cases per year) and disease progression. We review the main treatment approaches and new treatment options; EoE can be treated with topical corticosteroids such as fluticasone and budesonide, or dietary strategies, such as amino acid-based formulas, allergy test-directed elimination diets, and non-directed empiric elimination diets. Endoscopic dilation has also become an important tool for treatment of fibrostenostic complications of EoE. There are number of unresolved issues in EoE, including phenotypes, optimal treatment endpoints, the role of maintenance therapy, and treatment of refractory EoE. The care of patients with EoE and the study of the disease span many disciplinesEoE is ideally managed by a multidisciplinary team of gastroenterologists, allergists, pathologists, and dieticians. PMID:25109885

  1. Eosinophilic esophagitis: New insights in pathogenesis and therapy

    PubMed Central

    Guarino, Michele Pier Luca; Cicala, Michele; Behar, Jose

    2016-01-01

    Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multi-organ involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect. PMID:26855813

  2. Integrins are Mechanosensors That Modulate Human Eosinophil Activation

    PubMed Central

    Ahmadzai, Mustafa; Small, Mike; Sehmi, Roma; Gauvreau, Gail; Janssen, Luke J.

    2015-01-01

    Eosinophil migration to the lung is primarily regulated by the eosinophil-selective family of eotaxin chemokines, which mobilize intracellular calcium (Ca2+) and orchestrate myriad changes in cell structure and function. Eosinophil function is also known to be flow-dependent, although the molecular cognate of this mechanical response has yet to be adequately characterized. Using confocal fluorescence microscopy, we determined the effects of fluid shear stress on intracellular calcium concentration ([Ca2+]i) in human peripheral blood eosinophils by perfusing cells in a parallel-plate flow chamber. Our results indicate that fluid perfusion evokes a calcium response that leads to cell flattening, increase in cell area, shape change, and non-directional migration. None of these changes are seen in the absence of a flow stimulus, and all are blocked by chelation of intracellular Ca2+ using BAPTA. These changes are enhanced by stimulating the cells with eotaxin-1. The perfusion-induced calcium response (PICR) could be blocked by pre-treating cells with selective (CDP-323) and non-selective (RGD tripeptides) integrin receptor antagonists, suggesting that ?4?7/?4?1 integrins mediate this response. Overall, our study provides the first pharmacological description of a molecular mechanosensor that may collaborate with the eotaxin-1 signaling program in order to control human eosinophil activation. PMID:26539194

  3. Eosinophil Ribonucleases and Their Cutaneous Lesion-Forming Activity1

    PubMed Central

    Plager, Douglas A.; Davis, Mark D. P.; Andrews, Amy G.; Coenen, Michael J.; George, Terry J.; Gleich, Gerald J.; Leiferman, Kristin M.

    2010-01-01

    Eosinophil granule proteins are deposited in cutaneous lesions in many human diseases, but how these proteins contribute to pathophysiology is obscure. We injected eosinophil cationic protein (ECP or RNase 3), eosinophil-derived neurotoxin (EDN or RNase 2), eosinophil peroxidase (EPO), and major basic protein-1 (MBP1) intradermally into guinea pig and rabbit skin. ECP and EDN each induced distinct skin lesions at ? 2.5 ?M that began at 2 days, peaking about 7 days and persisting up to 6 weeks. These lesions were ulcerated (ECP) or crusted (EDN) with marked cellular infiltration. EPO and MBP1, 10 ?M, each produced perceptible induration and erythema with moderate cellular infiltration resolving within 2 weeks. ECP and EDN localized to dermal cells within 2 days whereas EPO and MBP1 remained extracellular. Overall, cellular localization and RNase activity of ECP and EDN were critical for lesion formation; differential glycosylation, net cationic charge, or RNase activity alone did not account for lesion formation. Ulcerated lesions from patients with the hypereosinophilic syndrome showed ECP and EDN deposition comparable to that in guinea pig skin. In conclusion, ECP and EDN disrupt skin integrity and cause inflammation. Their presence in ulcerative skin lesions may explain certain findings in human eosinophil-associated diseases. PMID:19717523

  4. Eosinophilic Colitis: University of Minnesota Experience and Literature Review

    PubMed Central

    Gaertner, Wolfgang B.; MacDonald, Jennifer E.; Kwaan, Mary R.; Shepela, Christopher; Madoff, Robert; Jessurun, Jose; Melton, Genevieve B.

    2011-01-01

    Eosinophilic colitis is a rare form of primary eosinophilic gastrointestinal disease that is poorly understood. Neonates and young adults are more frequently affected. Clinical presentation is highly variable depending on the depth of inflammatory response (mucosal, transmural, or serosal). The pathophysiology of eosinophilic colitis is unclear but is suspected to be related to a hypersensitivity reaction given its correlation with other atopic disorders and clinical response to corticosteroid therapy. Diagnosis is that of exclusion and differential diagnoses are many because colonic tissue eosinophilia may occur with other colitides (parasitic, drug-induced, inflammatory bowel disease, and various connective tissue disorders). Similar to other eosinophilic gastrointestinal disorders, steroid-based therapy and diet modification achieve very good and durable responses. In this paper, we present our experience with this rare pathology. Five patients (3 pediatric and 2 adults) presented with diarrhea and hematochezia. Mean age at presentation was 26 years. Mean duration of symptoms before pathologic diagnosis was 8 months. Mean eosinophil count per patient was 31 per high-power field. The pediatric patients responded very well to dietary modifications, with no recurrences. The adult patients were treated with steroids and did not respond. Overall mean followup was 22 (range, 248) months. PMID:21837236

  5. Eosinophilic esophagitis: New insights in pathogenesis and therapy.

    PubMed

    Guarino, Michele Pier Luca; Cicala, Michele; Behar, Jose

    2016-02-01

    Eosinophilic esophagitis (EoE) is a clinico-pathological entity with esophageal symptoms and dense esophageal eosinophilic infiltration throughout the esophagus that may persist despite treatment with proton pump inhibitors. This eosinophilic infiltration is usually absent in the stomach, small intestine and colon, although there are a number of reports of patients with a multi-organ involvement. EoE is associated with abnormalities involving TH2-dependent immunity, with multiple environmental factors strongly contributing to disease expression. The layer of the esophagus affected by the eosinophilic infiltration causes the specific symptoms. Esophageal involvement results mostly in dysphagia for solids that can be severe enough to cause recurrent esophageal obstruction with typical endoscopic features suggesting esophageal remodeling and pathological changes of eosinophilic infiltration of the mucosa, sub-epithelial fibrosis and muscle hypertrophy. This disease is frequently associated with other allergic conditions such as allergic asthma, allergic dermatitis and eosinophilia. The treatment of patients with EoE depends on the severity of the symptoms and of the inflammatory process as well as to their response to a gradual step-up treatment. The first line of treatment consists of steroid containing local inhalers. If unresponsive they are then treated with oral steroids. Intravenous interleukin blockers seem to have a consistent positive therapeutic effect. PMID:26855813

  6. Computed tomographic characteristics of eosinophilic pulmonary granulomatosis in five dogs.

    PubMed

    Fina, Caroline; Vignoli, Massimo; Terragni, Rossella; Rossi, Federica; Wisner, Erik; Saunders, Jimmy H

    2014-01-01

    Canine pulmonary eosinophilic granulomatosis is a rare inflammatory pulmonary disease characterized by formation of eosinophilic granulomas that tend to obliterate the normal pulmonary architecture. The purpose of this retrospective study was to describe the CT characteristics of confirmed idiopathic pulmonary eosinophilic granulomatosis in a group of dogs. Five dogs met inclusion criteria. All patients were young adult dogs of variable breeds. No dog had concurrent occult heartworm disease. Computed tomographic characteristics most commonly included pulmonary masses and nodules of variable size, and lesions were most commonly located in the caudal lung lobes. Four dogs had large pulmonary masses with or without additional nodules and one dog had nodular lesions disseminated throughout the entire lung parenchyma. All large eosinophilic granulomas were smoothly margined, heterogeneous pulmonary masses displaying heterogeneous contrast enhancement. A honeycomb-like enhancement pattern was observed in all but one mass and consisted of multiple hyperattenuating rims delineating central hypoattenuating areas, suggestive of bronchiectatic lung with peripheral enhancing airway walls and fluid-filled, necrotic bronchial lumen. One dog had evidence of tracheobronchial lymphadenopathy. Findings indicated that canine eosinophilic pulmonary granulomatosis should be included as a differential diagnosis for dogs with CT characteristics of multiple pulmonary masses and/or nodules in caudal lung lobes, and a honeycomb-like enhancement pattern in masses after intravenous administration of iodinated contrast medium. PMID:24102969

  7. Can We Determine Appropriate Foods to Eliminate to Treat Eosinophilic Esophagitis?

    MedlinePLUS

    ... treat Eosinophilic Esophagitis? Share | Can we determine appropriate foods to eliminate to treat Eosinophilic Esophagitis? Published Online: ... not normally present. The disease is due to food allergies in almost all pediatric patients, but standard ...

  8. Indigenous enteric eosinophils control DCs to initiate a primary Th2 immune response in vivo

    PubMed Central

    Chu, Derek K.; Jimenez-Saiz, Rodrigo; Verschoor, Christopher P.; Walker, Tina D.; Goncharova, Susanna; Llop-Guevara, Alba; Shen, Pamela; Gordon, Melissa E.; Barra, Nicole G.; Bassett, Jennifer D.; Kong, Joshua; Fattouh, Ramzi; McCoy, Kathy D.; Bowdish, Dawn M.; Erjef鄟t, Jonas S.; Pabst, Oliver; Humbles, Alison A.; Kolbeck, Roland; Waserman, Susan

    2014-01-01

    Eosinophils natively inhabit the small intestine, but a functional role for them there has remained elusive. Here, we show that eosinophil-deficient mice were protected from induction of Th2-mediated peanut food allergy and anaphylaxis, and Th2 priming was restored by reconstitution with il4+/+ or il4?/? eosinophils. Eosinophils controlled CD103+ dendritic cell (DC) activation and migration from the intestine to draining lymph nodes, events necessary for Th2 priming. Eosinophil activation in vitro and in vivo led to degranulation of eosinophil peroxidase, a granule protein whose enzymatic activity promoted DC activation in mice and humans in vitro, and intestinal and extraintestinal mouse DC activation and mobilization to lymph nodes in vivo. Further, eosinophil peroxidase enhanced responses to ovalbumin seen after immunization. Thus, eosinophils can be critical contributors to the intestinal immune system, and granule-mediated shaping of DC responses can promote both intestinal and extraintestinal adaptive immunity. PMID:25071163

  9. Recent Progress in the Research of Eosinophilic Esophagitis and Gastroenteritis.

    PubMed

    Kinoshita, Yoshikazu; Ishimura, Norihisa; Oshima, Naoki; Mikami, Hironobu; Okimoto, Eiko; Jiao, Di Jin; Ishihara, Shunji

    2016-01-01

    Eosinophilic esophagitis (EoE) and gastroenteritis are allergic gastrointestinal diseases mainly caused by food allergens. The number of patients with EoE is rapidly increasing in both Western and Asian countries. Basic knowledge of these diseases has mainly come from studies of EoE and Th2 type allergic reactions, including IL-5, IL-13, and IL-15, thymic stromal protein, and eotaxin 3, which are considered to have important roles. For a diagnosis of EoE, endoscopic abnormalities and histological confirmation of dense eosinophile infiltration in the esophageal epithelial layer are important, in addition to identifying dysphagia symptoms. As for eosinophilic gastroenteritis, blood test findings are more useful and the role of an endoscopic examination is reduced. For both diseases, the infection rate of Helicobacter pylori is lower than in healthy controls. Glucocorticoid administration is standard treatment for these diseases, while proton pump inhibitors are frequently effective for EoE. PMID:26789117

  10. Eosinophilic ulcer of the tongue--Case report.

    PubMed

    Didona, Dario; Paolino, Giovanni; Donati, Michele; Didona, Biagio; Calvieri, Stefano

    2015-01-01

    Eosinophilic ulcer of the oral mucosa is a rare, self-limiting, chronic and benign lesion of unknown pathogenesis that affects the oral mucosa. We present the case of a 65 year-old Caucasian female with a five month history of a painful ulcer on the lateral side of her tongue. The ulcer was not adhered to the underlying structures and there was no evidence of regional lymph node involvement. Laboratory examinations and X-rays revealed no abnormalities. Topical treatments had been performed without any improvement. Histopathological examination showed an ulcerated surface and mixed inflammatory infiltrate with several eosinophils extending into the mucosa and submucosa. No cellular atypia was observed. Based on the patient-s history and mucosal biopsy, a final diagnosis of eosinophilic ulcer of the oral mucosa was made. PMID:26312683

  11. Childhood-onset eosinophilic granulomatosis with polyangiitis: a rare childhood vasculitis mimicking anthrax and eosinophilic leukaemia.

    PubMed

    Sahin, Sezgin; Adrovic, Amra; Barut, Kenan; Kasapcopur, Ozgur

    2016-01-01

    A 14-year-old boy previously misdiagnosed as having cutaneous anthrax was referred with a 2-month history of multiple wide and deep ulceronecrotic lesions in the lower extremities, which occurred after contact with animals. Skin biopsy was compatible with vasculitis. Further examination at our hospital elicited eosinophilia and a history of asthma. On the second day of hospitalisation, he developed deep vein thrombosis. A diagnosis of eosinophilic granulomatosis with polyangiitis (EGPA) was established and intravenous methylprednisolone was administered. The patient showed remarkable improvement of the cutaneous lesions. Diagnosis of EGPA is challenging in the vasculitic phase and necessitates a detailed history that specifically questions the patient for an asthma background. This case illustrates a severe cutaneous presentation of EGPA and emphasises the difficulty of diagnosis as a result of overlapped signs and symptoms with cutaneous anthrax and leukaemia. EGPA should be kept in mind in the differential diagnosis of cutaneous lesions associated with eosinophilia. PMID:26887883

  12. Unsedated transnasal esophagoscopy for monitoring therapy in pediatric eosinophilic esophagitis

    PubMed Central

    Friedlander, Joel A.; DeBoer, Emily M.; Soden, Jason S.; Furuta, Glenn T.; Menard-Katcher, Calies D.; Atkins, Dan; Fleischer, David M.; Kramer, Robert E.; Deterding, Robin R.; Capocelli, Kelley E.; Prager, Jeremy D.

    2015-01-01

    Background and Aims Unsedated transnasal endoscopy (TNE) is safer and less costly than sedated EGD. The aim of this study was to evaluate the performance of TNE with biopsies in monitoring the esophageal mucosa of pediatric patients with eosinophilic esophagitis. Methods Patients between 8 and 17 years of age with eosinophilic esophagitis and their parents were enrolled. Unsedated TNE was performed. A 2.8-mm (1.2-mm channel) or a 4-mm flexible bronchoscope (2-mm channel) was used, and esophageal biopsy specimens were obtained. Biopsy specimen analysis, duration, adverse events, and billing charges of TNE were assessed. Immediately after TNE and a minimum of 2 weeks later, a modified Group Health Association of America 9 survey and a preference questionnaire were completed, respectively. Results Twenty-one of 22 enrolled patients underwent TNE. TNE was performed with no serious adverse events. Histopathological analysis revealed 0 eosinophils per high-power field (n = 12), fewer than 15 eosinophils per high-power field (n = 4), and more than 15 eosinophils per high-power field (n = 5). The total epithelial surface area of mucosal biopsy samples from either TNE Forceps (1.2 mm or 2 mm biopsy channel forceps) compared with those obtained during the subjects previous EGD by using standard endoscopic forceps was not statistically different (P = .308 [1.2 mm]/P = .492 [2 mm]). All parents and 76.2% of subjects would undergo the TNE again. TNE was preferred over EGD by 85.7% of parents and 52.4% of subjects. The modified Group Health Association of America 9 survey revealed a high degree of satisfaction (average, 43.19 2.6; maximum score, 45). Charges associated with TNE were 60.1% lower than for previous EGDs. Conclusions Unsedated TNE is an effective, lower-cost procedure for monitoring the esophageal mucosa of children with eosinophilic esophagitis. PMID:26142551

  13. Beta 2-adrenergic receptors on eosinophils. Binding and functional studies

    SciTech Connect

    Yukawa, T.; Ukena, D.; Kroegel, C.; Chanez, P.; Dent, G.; Chung, K.F.; Barnes, P.J. )

    1990-06-01

    We have studied the binding characteristics and functional effects of beta-adrenoceptors on human and guinea pig eosinophils. We determined the binding of the beta-antagonist radioligand (125I)pindolol (IPIN) to intact eosinophils obtained from the peritoneal cavity of guinea pigs and from blood of patients with eosinophilia. Specific binding was saturable, and Scatchard analysis showed a single binding site with a dissociation constant (Kd) of 24.6 pM and maximal number of binding sites (Bmax) of 7,166 per cell. ICI 118,551, a beta 2-selective antagonist, inhibited IPIN binding with a Ki value of 0.28 nM and was approximately 5,000-fold more effective than the beta 1-selective antagonist, atenolol. Isoproterenol increased cAMP levels about 5.5-fold above basal levels (EC50 = 25 microM); albuterol, a beta 2-agonist, behaved as a partial agonist with a maximal stimulation of 80%. Binding to human eosinophils gave similar results with a Kd of 25.3 pM and a Bmax corresponding to 4,333 sites per cell. Incubation of both human and guinea pig eosinophils with opsonized zymosan (2 mg/ml) or with phorbol myristate acetate (PMA) (10(-8) and 10(-6) M) resulted in superoxide anion generation and the release of eosinophil peroxidase; albuterol (10(-7) to 10(-5) M) had no inhibitory effect on the release of these products. Thus, eosinophils from patients with eosinophilia and from the peritoneal cavity of guinea pigs possess beta-receptors of the beta 2-subtype that are coupled to adenylate cyclase; however, these receptors do not modulate oxidative metabolism or degranulation. The possible therapeutic consequences of these observations to asthma are discussed.

  14. ?? T Lymphocytes Coordinate Eosinophil Influx during Allergic Responses

    PubMed Central

    de Oliveira Henriques, Maria Das Gra蓷s Muller; Penido, Carmen

    2012-01-01

    Tissue eosinophil infiltration, which is a hallmark of allergic and helminthic diseases, is mainly coordinated by T lymphocytes, via the production of eosinophilotactic chemokines. Among T lymphocyte subsets, lymphocytes expressing ?? T cell receptor have been determined as a key factor for eosinophil accumulation via direct and indirect mechanisms. This knowledge is strongly supported by the fact that, in different experimental models of eosinophilic airway inflammation and helminth-induced Th2 lung inflammation, an evident tissue accumulation of ?? T lymphocytes is observed. In addition, the depletion of ?? T lymphocytes is correlated with the impairment of eosinophil accumulation in inflamed tissue. ?? T lymphocytes are non-conventional T lymphocytes, which comprise a minor T lymphocyte subset, mainly distributed in the tissue, and present crucial roles in innate and acquired immune responses. ?? T lymphocytes recognize several danger- and pathogen-associated molecular pattern molecules and stress antigens in a MHC-independent fashion and can provide rapid tissue-specific responses, via the production of a wide range of chemical mediators capable to modulate other cell populations. These mediators include chemoattractant cytokines and chemokines that attract eosinophils into the tissue by either direct recognition (such as IL-5, CCL11/eotaxin), or indirect mechanisms via the modulation of ?? T lymphocytes and macrophages (through the production of interferon-?, IL-4, and CCL2/Monocyte chemoattractant protein-1, MCP-1, for example). The present review presents an overview of how ?? T lymphocytes coordinate eosinophil accumulation in allergy, by focusing on their role in airway inflammation and by discussing the involvement of cytokines and chemokines in this phenomenon. PMID:23316161

  15. What Is Chronic Myeloid Leukemia?

    MedlinePLUS

    ... Next Topic Normal bone marrow and blood What is chronic myeloid leukemia? Cancer starts when cells in ... treatment is the same as for adults. What is leukemia? Leukemia is a cancer that starts in ...

  16. What Is Chronic Lymphocytic Leukemia?

    MedlinePLUS

    ... Normal bone marrow, blood, and lymphoid tissue What is chronic lymphocytic leukemia? Cancer starts when cells in ... including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts in ...

  17. Atypical Presentation of Eosinophilic Fasciitis with Pitting Edema

    PubMed Central

    Lau, Matthew S

    2015-01-01

    Eosinophilic fasciitis (EF) is a rare condition involving inflammation of the fascia and peripheral eosinophilia of unknown etiology leading to tissue fibrosis. Clinical presentation includes peripheral eosinophilia, symmetrical skin thickening with subcutaneous tissue induration of the extremities and rashes developing acutely over a period of days to weeks. An unusual feature of EF is the presence of symmetric pitting edema presumed to be secondary to vascular leakage. This is a case of eosinophilic fasciitis presenting in atypical fashion with pitting peripheral edema in addition to the classic symptoms.

  18. IgE, Mast Cells, Basophils, and Eosinophils

    PubMed Central

    Stone, Kelly D.; Prussin, Calman; Metcalfe, Dean D.

    2010-01-01

    IgE, mast cells, basophils, and eosinophils are essential components of allergic inflammation. Antigen-specific IgE production, with subsequent fixation of IgE to Fc?RI receptors on mast cells and basophils, is central to the initiation and propagation of immediate hypersensitivity reactions. Mast cells, basophils, and eosinophils are central effector cells in allergic inflammation, as well as in innate and adaptive immunity. This review highlights what is known about these components and their roles in disease pathogenesis. PMID:20176269

  19. Eosinophilic esophagitis as paraneoplastic syndrome in a patient with ganglioneuroblastoma.

    PubMed

    Prader, S; Spalinger, J; Caduff, J; H羹rlimann, S; Rischewski, J

    2015-05-01

    A 16-month-old boy presented with failure to thrive despite sufficient caloric intake, hypersalivation, abdominal pain, chronic diarrhea and blepharitis. An eosinophilic esophagitis (EoE) was diagnosed by esophageal biopsy. Dietary restrictions and topical steroid treatment lead to no improvement. Further diagnostic work-up revealed an intrathoracal, paraspinal ganglioneuroblastoma. After operative extirpation of the tumour, all initial symptoms resolved. An esophageal control biopsy 4 weeks after tumour resection was normal. This is the first report of eosinophilic esophagitis as part of a paraneoplastic syndrome in a patient with a malignant disease other than a carcinoma. PMID:25985452

  20. Leukotriene B4 receptors on guinea pig alveolar eosinophils

    SciTech Connect

    Maghni, K.; de Brum-Fernandes, A.J.; Foeldes-Filep, E.G.; Gaudry, M.; Borgeat, P.; Sirois, P. )

    1991-09-01

    The existence of receptors for LTB4 on highly purified guinea pig alveolar eosinophils was investigated. Massive infiltration of eosinophils in alveolar spaces was induced in guinea pigs by i.v. injections of Sephadex beads G50 (16 mg/kg). Alveolar eosinophils (50 {times} 10(6) cells) were purified to approximately 98% by Percoll continuous density gradient centrifugation. The binding studies indicated that alveolar eosinophils bind LTB4 in a saturable, reversible and specific manner. Scatchard analysis indicated the existence of high-affinity binding sites (Kd1 = 1.00 {plus minus} 0.22 nM; Bmax1 = 966 {plus minus} 266 sites/cell) and low-affinity binding sites (Kd2 = 62.5 {plus minus} 8.9 nM; Bmax2 = 5557 {plus minus} 757 sites/cell). The metabolism of LTB4 by alveolar eosinophils in binding conditions was assessed by RP-HPLC and no significant degradation of (3H)LTB4 was observed. LTB4 dose-dependently stimulated eosinophil migration in both chemokinesis and chemotaxis assays with an EC50 value of 1.30 {plus minus} 0.14 and 18.14 {plus minus} 1.57 nM, respectively. LTB4 caused a dose-dependent increase in the production of superoxide anion with an apparent EC50 value of 50 {times} 10(-9) M in the authors experimental conditions. LTB4 also induced a dose-dependent increase in the generation of TxA2 with an EC50 value of 46.2 {times} 10(-9) M. Taken together, their results demonstrated that guinea pig alveolar eosinophils express two classes of specific receptors for LTB4. The high-affinity binding sites seem associated to chemokinesis and chemotaxis whereas the low-affinity binding sites seem associated to superoxide anion production and generation of TxA2. The existence of LTB4 receptors in eosinophils could explain the presence of these cells in hypersensitivity reactions.

  1. Case of invasive mucinous adenocarcinoma mimicking chronic eosinophilic pneumonia

    PubMed Central

    Beom, Jong Wook; Lee, Jong Hoo

    2014-01-01

    Invasive mucinous carcinoma is difficult to distinguish from other lung diseases; therefore, confirmation of the diagnosis may be delayed. A 64-year-old woman was admitted with a six-month history of cough, febrile sensation, and shortness of breath, with worsening symptoms. A computed tomography scan of the chest revealed bilateral homogenous ground-glass opacities and consolidation with subpleural predominance. The percentage of eosinophils in the serum and induced sputum was elevated and a diagnosis of chronic eosinophilic pneumonia was established. Despite administration of a systemic steroid, she did not rapidly respond. We performed a percutaneous needle biopsy and finally confirmed invasive mucinous adenocarcinoma.

  2. Recent advances in the treatment of eosinophilic esophagitis

    PubMed Central

    Schroeder, Shauna; Atkins, Dan; Furuta, Glenn T

    2013-01-01

    First described nearly 20 years ago, eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus characterized by eosinophilic infiltration of the esophageal epithelium. Over 50% of the current literature on EoE has been published in the last 3 years, signaling both a rising incidence and increased recognition of this disorder. Treatment options available for patients with EoE include dietary management and/or pharmacologic therapy. An individualized approach to treatment is preferred, with an emphasis on patientparental preference. The objective of this article is to discuss the current and future treatment options for EoE. PMID:20979557

  3. Acute myeloid leukemia

    MedlinePLUS

    ... However, the following things can lead to some types of leukemia, including AML: Blood disorders, including polycythemia vera, thrombocythemia, and myelodysplasia Certain chemicals (for example, benzene) ...

  4. Equine eosinophilic keratitis in horses: 28 cases (2003-2013).

    PubMed

    Edwards, Sydney; Clode, Alison B; Gilger, Brian C

    2015-12-01

    This retrospective case series evaluates husbandry and environmental conditions in relation to eosinophilic keratitis in horses. While no associations were found between disease and husbandry practices or specific environmental factors such as humidity or temperature, an increased prevalence of presentation in summer months was identified in this population of horses. PMID:26734136

  5. Eosinophil Recruitment in Type-2 Hypersensitivity Pulmonary Granulomas

    PubMed Central

    Shang, Xiao-Zhou; Chiu, Bo-Chin; Stolberg, Valerie; Lukacs, Nicholas W.; Kunkel, Steven L.; Murphy, Hedwig S.; Chensue, Stephen W.

    2002-01-01

    Monocyte chemotactic protein-3 (MCP-3/CCL7) has potent eosinophil chemoattractant properties. The present study determined its relative contribution to the formation of Th2 cytokine-mediated (type-2) eosinophil-rich interstitial lung granulomas induced by antigens of Schistosoma mansoni eggs. Both MCP-3 transcripts and protein levels were more strongly expressed in lungs with type-2 than with type-1 (mycobacterial antigen-elicited Th1-mediated) granulomas. In vivo treatment with neutralizing antibodies demonstrated that MCP-3 abrogated eosinophil accumulation in type-2 lesions by 40 to 50%. Immunohistochemical staining revealed that MCP-3 localized to vessels in or near granulomas suggesting that endothelial cells were an important in situ source of MCP-3. Maximal MCP-3 transcript expression was abrogated by anti-interleukin-4 treatment. Furthermore, cultured mouse lung endothelial cells displayed augmented MCP-3 production in response to interleukin-4. Together, these results suggest that MCP-3 contributes to a significant component of eosinophil recruitment in the type-2 interstitial granuloma formation and Th2 cytokines promote its production. PMID:12107110

  6. Unraveling the complexity of lipid body organelles in human eosinophils

    PubMed Central

    Melo, Rossana C. N.; Weller, Peter F.

    2014-01-01

    Lipid-rich organelles are common in many cell types. In cells, such as adipocytes, these organelles are termed LDs, whereas in other cells, such as leukocytes, they are called LBs. The study of leukocyte LBs has attracted attention as a result of their association with human diseases. In leukocytes, such as eosinophils, LB accumulation has been documented extensively during inflammatory conditions. In these cells, LBs are linked to the regulation of immune responses by compartmentalization of several proteins and lipids involved in the control and biosynthesis of inflammatory mediators (eicosanoids). However, it has been unclear how diverse proteins, including membrane-associated enzymes involved in eicosanoid formation, incorporate into LBs, especially if the internal content of LBs is assumed to consist solely of stores of neutral lipids, as present within adipocyte LDs. Studies of the formation, function, and ultrastructure of LBs in eosinophils have been providing insights pertinent to LBs in other leukocytes. Here, we review current knowledge of the composition and function of leukocyte LBs as provided by studies of human eosinophil LBs, including recognitions of the internal architecture of eosinophil LBs based on 3D electron tomographic analyses. PMID:25210147

  7. An update on the immunopathogenesis of eosinophilic esophagitis.

    PubMed

    Lucendo, Alfredo J; Lucendo, Baltasar

    2010-04-01

    Eosinophilic esophagitis (EoE) is a chronic clinicopathological entity characterized by large numbers of intraepithelial eosinophils infiltrating the esophageal mucosa, which is not caused by gastroesophageal reflux. This disease has become widely recognized over the past few years and new methods have been developed to reveal its underlying pathophysiological mechanisms. Owing to the high prevalence of food and/or airborne allergen sensitization in EoE patients, the allergic nature of the disease had to be defined, which has certain factors in common with other IgE-dependent entities, such as bronchial asthma or allergic rhinitis. Of these, some cytokines and chemokines previously studied in asthma have also been implicated in molecular mechanisms causing eosinophil-rich esophageal inflammation. However, the role played by IgE in relation to the esophageal eosinophilic infiltrate must be clarified, together with the possible function of mast cells in the inflammatory infiltrate and its activation stimuli. A putative role has also been recently suggested for gastroesophageal reflux in the origin of EoE that should be profoundly analyzed, together with the role of specific genes implicated in other digestive inflammatory disorders. This article reviews recent advances in the immunopathogenesis of EoE, which should also consider other pathways to activate the esophageal mucosal immune system. PMID:20350261

  8. Eosinophilic Gastrointestinal Disorder in Coeliac Disease: A Case Report and Review

    PubMed Central

    Lim, Dennis N. F.; Wilkins, Annelise; Horton, Laura Elizabeth; Ahmad, Ishfaq; Phillips, Chris

    2012-01-01

    Eosinophilic gastrointestinal disorder is a rare disorder characterised by eosinophilic infiltration of the gastrointestinal tract. There are various gastrointestinal manifestations with eosinophilic ascites being the most unusual and rare presentation. Diagnosis requires high index of suspicion and exclusion of various disorders associated with peripheral eosinophilia. There are no previous case reports to suggest an association between eosinophilic gastrointestinal disorder and coeliac disease in adults. We report a case of eosinophilic ascites and gastroenteritis in a 30-year-old woman with a known history of coeliac disease who responded dramatically to a course of steroids. PMID:23346427

  9. A Pilot Study of Omalizumab in Eosinophilic Esophagitis

    PubMed Central

    Loizou, Denise; Enav, Benjamin; Komlodi-Pasztor, Edina; Hider, Pamela; Kim-Chang, Julie; Noonan, Laura; Taber, Tabitha; Kaushal, Suhasini; Limgala, Renuka; Brown, Margaret; Gupta, Raavi; Balba, Nader; Goker-Alpan, Ozlem; Khojah, Amer; Alpan, Oral

    2015-01-01

    Eosinophilic disorders of the gastrointestinal tract are an emerging subset of immune pathologies within the spectrum of allergic inflammation. Eosinophilic Esophagitis (EoE), once considered a rare disease, is increasing in incidence, with a rate of over 1 in 10,000 in the US, for unknown reasons. The clinical management of EoE is challenging, thus there is an urgent need for understanding the etiology and pathophysiology of this eosinophilic disease to develop better therapeutic approaches. In this open label, single arm, unblinded study, we evaluated the effects of an anti-IgE treatment, omalizumab, on local inflammation in the esophagus and clinical correlates in patients with EoE. Omalizumab was administered for 12 weeks to 15 subjects with long standing EoE. There were no serious side effects from the treatment. Esophageal tissue inflammation was assessed both before and after therapy. After 3 months on omalizumab, although tissue Immunoglobulin E (IgE) levels were significantly reduced in all but two of the subjects, we found that full remission of EoE, which is defined as histologic and clinical improvement only in 33% of the patients. The decrease in tryptase-positive cells and eosinophils correlated significantly with the clinical outcome as measured by improvement in endoscopy and symptom scores, respectively. Omalizumab-induced remission of EoE was limited to subjects with low peripheral blood absolute eosinophil counts. These findings demonstrate that in a subset of EoE patients, IgE plays a role in the pathophysiology of the disease and that anti-IgE therapy with omalizumab may result in disease remission. Since this study is open label there is the potential for bias, hence the need for a larger double blind placebo controlled study. The data presented in this pilot study provides a foundation for proper patient selection to maximize clinical efficacy. Trial Registration ClinicalTrials.gov NCT01040598 PMID:25789989

  10. Eosinophils Contribute to Early Clearance of Pneumocystis murina Infection.

    PubMed

    Eddens, Taylor; Elsegeiny, Waleed; Nelson, Michael P; Horne, William; Campfield, Brian T; Steele, Chad; Kolls, Jay K

    2015-07-01

    Pneumocystis pneumonia remains a common opportunistic infection in the diverse immunosuppressed population. One clear risk factor for susceptibility to Pneumocystis is a declining CD4(+) T cell count in the setting of HIV/AIDS or primary immunodeficiency. Non-HIV-infected individuals taking immunosuppressive drug regimens targeting T cell activation are also susceptible. Given the crucial role of CD4(+) T cells in host defense against Pneumocystis, we used RNA sequencing of whole lung early in infection in wild-type and CD4-depleted animals as an unbiased approach to examine mechanisms of fungal clearance. In wild-type mice, a strong eosinophil signature was observed at day 14 post Pneumocystis challenge, and eosinophils were increased in the bronchoalveolar lavage fluid of wild-type mice. Furthermore, eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice were more susceptible to Pneumocystis infection when compared with BALB/c controls, and bone marrow-derived eosinophils had in vitro Pneumocystis killing activity. To drive eosinophilia in vivo, Rag1(-/-) mice were treated with a plasmid expressing IL-5 (pIL5) or an empty plasmid control via hydrodynamic injection. The pIL5-treated mice had increased serum IL-5 and eosinophilia in the lung, as well as reduced Pneumocystis burden, compared with mice treated with control plasmid. In addition, pIL5 treatment could induce eosinophilia and reduce Pneumocystis burden in CD4-depleted C57BL/6 and BALB/c mice, but not eosinophilopoiesis-deficient Gata1(tm6Sho)/J mice. Taken together, these results demonstrate that an early role of CD4(+) T cells is to recruit eosinophils to the lung and that eosinophils are a novel candidate for future therapeutic development in the treatment of Pneumocystis pneumonia in the immunosuppressed population. PMID:25994969

  11. Interleukin-5 pathway inhibition in the treatment of eosinophilic respiratory disorders: evidence and unmet needs

    PubMed Central

    Varricchi, Gilda; Bagnasco, Diego; Borriello, Francesco; Heffler, Enrico; Canonica, Giorgio W.

    2016-01-01

    Purpose of review Human eosinophils were first identified and named by Paul Ehrlich in 1879 on the basis of the cell's granular uptake of eosin. Although eosinophils represent approximately 1% of peripheral blood leukocytes, they have the propensity to leave the blood stream and migrate into inflamed tissues. Eosinophils and their mediators are critical effectors to asthma and eosinophilic granulomatosis with polyangiitis (EGPA). Eosinophils are equipped with a large number of cell-surface receptors and produce specific cytokines and chemokines. Recent findings Eosinophils are the major source of interleukin-5 and highly express the interleukin-5R帢 on their surface. Clinical trials evaluating monoclonal antibodies to interleukin-5 (mepolizumab and reslizumab) and its receptor interleukin-5R帢 (benralizumab) have been or are underway in patients with eosinophilic asthma, EGPA and chronic obstructive pulmonary disease (COPD). Overall, targeting interleukin-5/interleukin-5R帢 is associated with a marked decrease in blood and sputum eosinophilia, the number of exacerbations and improvement of some clinical parameters in adult patients with severe eosinophilic asthma. Pilot studies suggest that mepolizumab might be a glucocorticoid-sparing treatment in patients with EGPA. A preliminary study found that benralizumab did not reduce the exacerbations and did modify lung function in patients with eosinophilic COPD. Summary The review examines recent advances in the biology of eosinophils and how targeting the interleukin-5 pathway might offer benefit to some patients with severe asthma, EGPA, and COPD. Interleukin-5/interleukin-5R帢-targeted treatments offer promises to patients with eosinophilic respiratory disorders. PMID:26859368

  12. Targeted ablation of miR-21 decreases murine eosinophil progenitor cell growth.

    PubMed

    Lu, Thomas X; Lim, Eun-Jin; Itskovich, Svetlana; Besse, John A; Plassard, Andrew J; Mingler, Melissa K; Rothenberg, Joelle A; Fulkerson, Patricia C; Aronow, Bruce J; Rothenberg, Marc E

    2013-01-01

    MiR-21 is one of the most up-regulated miRNAs in multiple allergic diseases associated with eosinophilia and has been shown to positively correlate with eosinophil levels. Herein, we show that miR-21 is up-regulated during IL-5-driven eosinophil differentiation from progenitor cells in vitro. Targeted ablation of miR-21 leads to reduced eosinophil progenitor cell growth. Furthermore, miR-21(-/-) eosinophil progenitor cells have increased apoptosis as indicated by increased levels of annexin V positivity compared to miR-21(+/+) eosinophil progenitor cells. Indeed, miR-21(-/-) mice have reduced blood eosinophil levels in vivo and reduced eosinophil colony forming unit capacity in the bone marrow. Using gene expression microarray analysis, we identified dysregulation of genes involved in cell proliferation (e,g, Ms4a3, Grb7), cell cycle and immune response as the most significant pathways affected by miR-21 in eosinophil progenitors. These results demonstrate that miR-21 can regulate the development of eosinophils by influencing eosinophil progenitor cell growth. Our findings have identified one of the first miRNAs with a role in regulating eosinophil development. PMID:23533623

  13. Targeted Ablation of miR-21 Decreases Murine Eosinophil Progenitor Cell Growth

    PubMed Central

    Lu, Thomas X.; Lim, Eun-Jin; Itskovich, Svetlana; Besse, John A.; Plassard, Andrew J.; Mingler, Melissa K.; Rothenberg, Joelle A.; Fulkerson, Patricia C.; Aronow, Bruce J.; Rothenberg, Marc E.

    2013-01-01

    MiR-21 is one of the most up-regulated miRNAs in multiple allergic diseases associated with eosinophilia and has been shown to positively correlate with eosinophil levels. Herein, we show that miR-21 is up-regulated during IL-5-driven eosinophil differentiation from progenitor cells in vitro. Targeted ablation of miR-21 leads to reduced eosinophil progenitor cell growth. Furthermore, miR-21?/? eosinophil progenitor cells have increased apoptosis as indicated by increased levels of annexin V positivity compared to miR-21+/+ eosinophil progenitor cells. Indeed, miR-21?/? mice have reduced blood eosinophil levels in vivo and reduced eosinophil colony forming unit capacity in the bone marrow. Using gene expression microarray analysis, we identified dysregulation of genes involved in cell proliferation (e,g, Ms4a3, Grb7), cell cycle and immune response as the most significant pathways affected by miR-21 in eosinophil progenitors. These results demonstrate that miR-21 can regulate the development of eosinophils by influencing eosinophil progenitor cell growth. Our findings have identified one of the first miRNAs with a role in regulating eosinophil development. PMID:23533623

  14. A Functional ??TCR/CD3 Complex Distinct from ??T Cells Is Expressed by Human Eosinophils

    PubMed Central

    Woerly, Ga褮ane; Loiseau, Sylvie; Hermann, Emmanuel; Fourni, Jean-Jacques; H幨iot, Laurent; Mattot, Virginie; Soncin, Fabrice; Gougeon, Marie-Lise; Dombrowicz, David; Capron, Monique

    2009-01-01

    Background Eosinophils are effector cells during parasitic infections and allergic responses. However, their contribution to innate immunity has been only recently unravelled. Methodology/Principal Findings Here we show that human eosinophils express CD3 and ?? T Cell Receptor (TCR) but not ?? TCR. Surface expression of ??TCR/CD3 is heterogeneous between eosinophil donors and inducible by mycobacterial ligands. Surface immunoprecipitation revealed expression of the full ??TCR/CD3 complex. Real-time PCR amplification for CD3, ? and ? TCR constant regions transcripts showed a significantly lower expression in eosinophils than in ??T cells. Limited TCR rearrangements occur in eosinophils as shown by spectratyping analysis of CDR3 length profiles and in situ hybridization. Release by eosinophils of Reactive Oxygen Species, granule proteins, Eosinophil Peroxidase and Eosinophil-Derived Neurotoxin and cytokines (IFN-? and TNF-?) was observed following activation by ??TCR-specific agonists or by mycobacteria. These effects were inhibited by anti-??TCR blocking antibodies and antagonists. Moreover, ??TCR/CD3 was involved in eosinophil cytotoxicity against tumor cells. Conclusions/Significance Our results provide evidence that human eosinophils express a functional ??TCR/CD3 with similar, but not identical, characteristics to ??TCR from ??T cells. We propose that this receptor contributes to eosinophil innate responses against mycobacteria and tumors and may represent an additional link between lymphoid and myeloid lineages. PMID:19536290

  15. Eosinophil-Associated Lung Diseases. A Cry for Surfactant Proteins A and D Help?

    PubMed Central

    Ledford, Julie G.; Addison, Kenneth J.; Foster, Matthew W.

    2014-01-01

    Surfactant proteins (SP)-A and SP-D (SP-A/-D) play important roles in numerous eosinophil-dominated diseases, including asthma, allergic bronchopulmonary aspergillosis, and allergic rhinitis. In these settings, SP-A/-D have been shown to modulate eosinophil chemotaxis, inhibit eosinophil mediator release, and mediate macrophage clearance of apoptotic eosinophils. Dysregulation of SP-A/-D function in eosinophil-dominated diseases is also not uncommon. Alterations in serum SP-A/-D levels are associated with disease severity in allergic rhinitis and chronic obstructive pulmonary disease. Furthermore, oligimerization of SP-A/-D, necessary for their proper function, can be perturbed by reactive nitrogen species, which are increased in eosinophilic disease. In this review, we highlight the associations of eosinophilic lung diseases with SP-A and SP-D levels and functions. PMID:24960334

  16. Therapeutic Strategies for Harnessing Human Eosinophils in Allergic Inflammation, Hypereosinophilic Disorders, and Cancer

    PubMed Central

    Amini-Vaughan, Zhaleh J.; Martinez-Moczygemba, Margarita; Huston, David P.

    2013-01-01

    The eosinophil is a multifunctional granulocyte best known for providing host defense against parasites. Paradoxically, eosinophils are also implicated in the pathogenesis of allergic inflammation, asthma, and hypereosinophilic syndromes. Emerging evidence also supports the potential for harnessing the cytotoxic power of eosinophils and redirecting it to kill solid tumors. Central to eosinophil physiology is interleukin-5 (IL-5) and its receptor (IL-5R) which is composed of a ligand-specific alpha chain (IL-5R帢) and the common beta chain (帣c). Eosinophil activation can lead to their degranulation, resulting in rapid release of an arsenal of tissue-destructive proinflammatory mediators and cytotoxic proteins that can be both beneficial and detrimental to the host. This review discusses eosinophil immunobiology and therapeutic strategies for targeting of IL-5 and IL-5R, as well as the potential for harnessing eosinophil cytotoxicity as a tumoricide. PMID:22875242

  17. Curcumin alleviates eosinophilic meningitis through reduction of eosinophil count following albendazole treatment against Angiostrongylus cantonensis in mice.

    PubMed

    Shyu, Ling-Yuh; Chang, Han-Hsin; Hsu, Jeng-Dong; Lin, David Pei-Cheng; Teng, Ying-Hock; Lee, Hsiu-Hsiung

    2012-03-01

    Angiostrongylus cantonensis (A. cantonensis) is the most common cause of parasitic eosinophilic meningitis worldwide. By using an animal model of BALB/c mice infected with A. cantonensis, previous studies indicated that the anthelmintic drug, albendazole, could kill A. cantonensis larvae and prevent further infection. However, the dead larvae will induce severe immune responses targeting at brain tissues. To alleviate the detrimental effects caused by the dead larvae, we administered curcumin, a traditional anti-inflammatory agent, as a complementary treatment in addition to albendazole therapy, to determine whether curcumin could be beneficial for treatment. The results showed that although curcumin treatment alone did not reduce worm number, combined treatment by albendazole and curcumin helped to reduce eosinophil count in the cerebrospinal fluid, better than using albendazole alone. This alleviating effect did not affect albendazole treatment alone, since histological analysis showed similar worm eradication with or without addition of curcumin. Nevertheless, curcumin treatment alone and combined albendazole-curcumin treatment did not inhibit MMP-9 expression in the brain tissue. In conclusion, curcumin, when used as a complementary treatment to albendazole, could help to alleviate eosinophilic meningitis through suppression of eosinophil count in the cerebrospinal fluid. PMID:22053741

  18. Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-09

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  19. 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

  20. 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

  1. Vesicle-mediated secretion of human eosinophil granule-derived major basic protein.

    PubMed

    Melo, Rossana C N; Spencer, Lisa A; Perez, Sandra A C; Neves, Josiane S; Bafford, Staci P; Morgan, Ellen S; Dvorak, Ann M; Weller, Peter F

    2009-07-01

    Major basic protein (MBP), the predominant cationic protein of human eosinophil specific granules, is stored within crystalloid cores of these granules. Secretion of MBP contributes to the immunopathogenesis of varied diseases. Prior electron microscopy (EM) of eosinophils in sites of inflammation noted losses of granule cores in the absence of granule exocytosis and suggested that eosinophil granule proteins might be released through piecemeal degranulation (PMD), a secretory process mediated by transport vesicles. Because release of eosinophil granule-derived MBP through PMD has not been studied, we evaluated secretion of this cationic protein by human eosinophils. Intracellular localizations of MBP were studied within nonstimulated and eotaxin-stimulated human eosinophils by both immunofluorescence and a pre-embedding immunonanogold EM method that enables optimal epitope preservation and antigen access to membrane microdomains. In parallel, quantification of transport vesicles was assessed in eosinophils from a patient with hypereosinophilic syndrome (HES). Our data demonstrate vesicular trafficking of MBP within eotaxin-stimulated eosinophils. Vesicular compartments, previously implicated in transport from granules to the plasma membrane, including large vesiculotubular carriers termed eosinophil sombrero vesicles (EoSVs), were found to contain MBP. These secretory compartments were significantly increased in numbers within HES eosinophils. Moreover, in addition to granule-stored MBP, even unstimulated eosinophils contained appreciable amounts of MBP within secretory vesicles, as evidenced by immunonanogold EM and immunofluorescent colocalizations of MBP and CD63. These data suggest that eosinophil MBP, with its multiple extracellular activities, can be mobilized from granules by PMD into secretory vesicles and both granule- and secretory vesicle-stored pools of MBP are available for agonist-elicited secretion of MBP from human eosinophils. The recognition of PMD as a secretory process to release MBP is important to understand the pathological basis of allergic and other eosinophil-associated inflammatory diseases. PMID:19398958

  2. Immunotoxins for leukemia

    PubMed Central

    FitzGerald, David J.; Kreitman, Robert J.; Pastan, Ira

    2014-01-01

    Unconjugated monoclonal antibodies that target hematopoietic differentiation antigens have been developed to treat hematologic malignancies. Although some of these have activity against chronic lymphocytic leukemia and hairy cell leukemia, in general, monoclonal antibodies have limited efficacy as single agents in the treatment of leukemia. To increase their potency, the binding domains of monoclonal antibodies can be attached to protein toxins. Such compounds, termed immunotoxins, are delivered to the interior of leukemia cells based on antibody specificity for cell surface target antigens. Recombinant immunotoxins have been shown to be highly cytotoxic to leukemic blasts in vitro, in xenograft model systems, and in early-phase clinical trials in humans. These agents will likely play an increasing role in the treatment of leukemia. PMID:24578503

  3. 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

    2015-07-21

    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

  4. Treatment Options for Hairy Cell Leukemia

    MedlinePLUS

    ... Childhood ALL Treatment Childhood AML Treatment Research Hairy Cell Leukemia TreatmentPatient Version (PDQ簧) General Information About Hairy Cell Leukemia Key Points Hairy cell leukemia is a ...

  5. General Information about Hairy Cell Leukemia

    MedlinePLUS

    ... Childhood ALL Treatment Childhood AML Treatment Research Hairy Cell Leukemia TreatmentPatient Version (PDQ簧) General Information About Hairy Cell Leukemia Key Points Hairy cell leukemia is a ...

  6. Carbonic anhydrase IV (CAR4) is expressed on IL-5 activated murine eosinophils

    PubMed Central

    Wen, Ting; Mingler, Melissa K.; Wahl, Benjamin; Khorki, M. Eyad; Pabst, Oliver; Zimmermann, Nives; Rothenberg, Marc E.

    2014-01-01

    Eosinophilia and its cellular activation are hallmark features of asthma, as well as other allergic/TH2 disorders, yet there are few, if any, reliable surface markers of eosinophil activation. We have employed a FACS-based genome-wide screening system to identify transcriptional alterations in murine lung eosinophils recruited and activated by pulmonary allergen exposure. Using a relatively stringent screen with false-positive correction, we identified 82 candidate genes that could serve as eosinophil activation markers and/or pathogenic effector markers in asthma. Carbonic anhydrase IV (Car4) was a top dysregulated gene with 36-fold induction in allergen-elicited pulmonary eosinophils, which was validated by quantitative PCR, IHC and by flow cytometry. Eosinophil CAR4 expression was kinetically regulated by IL-5 but not IL-13. IL-5 was both necessary and sufficient for induction of eosinophil CAR4. While CAR4-deficient mice did not have a defect in eosinophil recruitment to the lung nor a change in eosinophil pH-buffering capacity, allergen-challenged chimeric mice that contained Car4?/? hematopoietic cells aberrantly expressed a series of genes enriched in biological processes involved in epithelial differentiation, keratinization, and anion exchange. In conclusion, we have determined that eosinophils express CAR4 following IL-5 or allergen exposure, and that CAR4 is involved in regulating the lung transcriptome associated with allergic airway inflammation; as such, CAR4 has potential value for diagnosing and monitoring eosinophilic responses. PMID:24808371

  7. Carbonic anhydrase IV is expressed on IL-5-activated murine eosinophils.

    PubMed

    Wen, Ting; Mingler, Melissa K; Wahl, Benjamin; Khorki, M Eyad; Pabst, Oliver; Zimmermann, Nives; Rothenberg, Marc E

    2014-06-15

    Eosinophilia and its cellular activation are hallmark features of asthma, as well as other allergic/Th2 disorders, yet there are few, if any, reliable surface markers of eosinophil activation. We have used a FACS-based genome-wide screening system to identify transcriptional alterations in murine lung eosinophils recruited and activated by pulmonary allergen exposure. Using a relatively stringent screen with false-positive correction, we identified 82 candidate genes that could serve as eosinophil activation markers and/or pathogenic effector markers in asthma. Carbonic anhydrase IV (Car4) was a top dysregulated gene with 36-fold induction in allergen-elicited pulmonary eosinophils, which was validated by quantitative PCR, immunohistochemistry, and flow cytometry. Eosinophil CAR4 expression was kinetically regulated by IL-5, but not IL-13. IL-5 was both necessary and sufficient for induction of eosinophil CAR4. Although CAR4-deficient mice did not have a defect in eosinophil recruitment to the lung, nor a change in eosinophil pH-buffering capacity, allergen-challenged chimeric mice that contained Car4(-/-) hematopoietic cells aberrantly expressed a series of genes enriched in biological processes involved in epithelial differentiation, keratinization, and anion exchange. In conclusion, we have determined that eosinophils express CAR4 following IL-5 or allergen exposure, and that CAR4 is involved in regulating the lung transcriptome associated with allergic airway inflammation; therefore, CAR4 has potential value for diagnosing and monitoring eosinophilic responses. PMID:24808371

  8. Purinergic P2Y12 Receptor Activation in Eosinophils and the Schistosomal Host Response

    PubMed Central

    Muniz, Valdirene S.; Baptista-dos-Reis, Renata; Benjamim, Claudia F.; Mata-Santos, Hilton A.; Pyrrho, Alexandre S.; Strauch, Marcelo A.; Melo, Paulo A.; Vicentino, Amanda R. R.; Silva-Paiva, Juliana; Bandeira-Melo, Christianne; Weller, Peter F.; Figueiredo, Rodrigo T.; Neves, Josiane S.

    2015-01-01

    Identifying new target molecules through which eosinophils secrete their stored proteins may reveal new therapeutic approaches for the control of eosinophilic disorders such as host immune responses to parasites. We have recently reported the expression of the purinergic P2Y12 receptor (P2Y12R) in human eosinophils; however, its functional role in this cell type and its involvement in eosinophilic inflammation remain unknown. Here, we investigated functional roles of P2Y12R in isolated human eosinophils and in a murine model of eosinophilic inflammation induced by Schistosoma mansoni (S. mansoni) infection. We found that adenosine 5-diphosphate (ADP) induced human eosinophils to secrete eosinophil peroxidase (EPO) in a P2Y12R dependent manner. However, ADP did not interfere with human eosinophil apoptosis or chemotaxis in vitro. In vivo, C57Bl/6 mice were infected with cercariae of the Belo Horizonte strain of S. mansoni. Analyses performed 55 days post infection revealed that P2Y12R blockade reduced the granulomatous hepatic area and the eosinophilic infiltrate, collagen deposition and IL-13/IL-4 production in the liver without affecting the parasite oviposition. As found for humans, murine eosinophils also express the P2Y12R. P2Y12R inhibition increased blood eosinophilia, whereas it decreased the bone marrow eosinophil count. Our results suggest that P2Y12R has an important role in eosinophil EPO secretion and in establishing the inflammatory response in the course of a S. mansoni infection. PMID:26448282

  9. Eosinophil and neutrophil extracellular DNA traps in human allergic asthmatic airways

    PubMed Central

    Dworski, Ryszard; Simon, Hans-Uwe; Hoskins, Aimee; Yousefi, Shida

    2011-01-01

    Background Asthma is a heterogeneous inflammatory airway disorder which involves eosinophilic and non-eosinophilic phenotypes. Unlike in normal lungs, eosinophils are often present in atopic asthmatic airways although a subpopulation of asthmatic subjects predominantly develops neutrophilic inflammation. Recently, it has been demonstrated that eosinophils and neutrophils generate bactericidal extracellular traps consisting of DNA and cytotoxic granule proteins. Objective To explore if living eosinophils and neutrophils infiltrating human atopic asthmatic airways actively form extracellular DNA traps in vivo. Methods Quantitative analysis of eosinophils-releasing DNA was performed in endobronchial biopsies from 20 mild human atopic asthmatics at baseline and after local allergen challenge, and 10 normal subjects. DNA was stained with propidium iodine and major basic protein (MBP) with specific antibody. Differential cell counts and cytokines/chemokines were assessed in bronchoalveolar fluids. Results Asthmatic airways were infiltrated with a significantly higher number of eosinophils than normal airways (39.34.6 vs. 0.40.9, p<0.0001). All asthmatics but only one control subject expressed eosinophils releasing DNA that colocalized with MBP (33.6520.33 vs. 0.30.9 per hpf, p<0.0001). Four asthmatics mostly expressed neutrophilic inflammation and neutrophil DNA traps. Allergen challenge had no significant quantitative effect on eosinophil or neutrophil DNA traps. Airway eosinophils or DNA traps did not correlate with either BAL levels of IL-5, IFN-?, or eotaxin, or the provoking doses of methacholine or allergen in asthmatics. Conclusions Extracellular DNA traps are generated by eosinophils and neutrophils in human atopic asthmatic airways in vivo. The mechanism and role of this new finding will necessitate further investigation. Clinical implications Eosinophil extracellular traps (EETs) (1) are frequently seen in atopic asthma, (2) consist of DNA and granule proteins, and (3) might be a new useful biomarker reflecting eosinophil activation. PMID:21315435

  10. Activation of ?1 Integrins on Blood Eosinophils by P-Selectin

    PubMed Central

    Mosher, Deane F.

    2011-01-01

    Activation of ?1 integrins of blood eosinophils, assessed by mAb N29, correlates inversely with FEV1 in two paradigms for studying control of human asthma. We asked whether P-selectin causes eosinophil ?1 integrin activation and results in increased adhesivity. By dual-label flow cytometry, eosinophils with high levels of surface-associated P-selectin had higher reactivity with the activation-sensitive anti-?1 mAbs N29, 8E3, and 9EG7 than eosinophils with no or with a low-level of surface-associated P-selectin. Among patients with nonsevere asthma, surface P-selectin correlated with N29, 8E3, and 9EG7 signals. By immunofluorescence microscopy, surface-associated P-selectin was present in patches on eosinophils, some of which stained for the platelet marker thrombospondin-1. Activated ?1 and P-selectin partially colocalized on eosinophils. Soluble P-selectin added to whole blood enhanced activation of eosinophil ?1, but not ?2, integrins. In contrast, IL-5 activated eosinophil ?2, but not ?1, integrins. Eosinophils that did not attach to vascular cell adhesion molecule-1 (VCAM-1) in a static adhesion assay had a lower N29 signal than the original population. Soluble P-selectin added to whole blood enhanced eosinophil adhesion to VCAM-1. These findings are compatible with a scenario whereby P-selectin, on eosinophil-associated activated platelets or acquired from plasma or from prior interactions with endothelial cells or platelets, activates eosinophil ?4?1 integrin and stimulates eosinophils to adhere to VCAM-1 and move to the airway in asthma. PMID:21441381

  11. Emphysematous Eosinophilic Lymphangitis in the Ruminal Submucosa of Cattle.

    PubMed

    Ohfuji, S

    2015-11-01

    Twenty cattle (14 Holstein-Friesian, 3 Japanese Black, 3 Aberdeen Angus) ranging in age from 3 months to 8 years exhibited, at slaughter, emphysematous thickening of the ruminal submucosa owing to the appearance of numerous, contiguous, small gas bubbles. Microscopic changes in the ruminal submucosa consisted of (1) multiple cystic (emphysematous) lymphangiectasis that was frequently lined or occluded by granulomatous inflammatory infiltrates including macrophages, multinucleate giant cells, and eosinophils; (2) intralymphatic phagocytosis by macrophages and giant cells of eosinophils that showed positive labeling with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end-labeling assay; and (3) an inflammatory infiltrate extending from the area of lymphangitis into surrounding tissue, as well as edema, hemorrhage, fibrin exudation, fibroplasia, or capillary proliferation throughout the lesional submucosa. In addition, 15 (75%) of the cattle had globular leukocyte infiltrates in the mucosal epithelia of the rumen. PMID:25710949

  12. [Eosinophilic proctocolitis induced by foods. Report of a case].

    PubMed

    Cordero Miranda, Miguel Angel; Bland鏮 Vijil, Virginia; Reyes Ruiz, Norma Isabel; Avila Casta嚧n, Lourdes; del R甐 Navarro, Blanca Estela; Garc燰 Aranda, Jos Alberto; Blanco Rodr璲uez, Gerardo; Sienra Monge, Juan Jos Luis

    2002-01-01

    The food-induced eosinophilic proctocolitis is a major cause of blood-tinged stools and appears in the first two months of life. The infant is generally described as well, but the clinical features and laboratory results are often nonspecific. We present an early infant with fresh blood stools at 50 days. The colonoscopy and biopsy of the rectum and lower sigmoid revealed lymphoid nodular hyperplasia of the submucose and eosinophil infiltration (40 to 50 per high power field) of the lamina propria and intraepithelial. Elimination of the offending protein from the diet, through the use of an extensively hydrolyzed casein-based formula and soy, lead to clinical resolution of bleeding at 48 hours. We made a review of the case. PMID:12561652

  13. Eosinophilic Pneumonia in a Patient with Bronchial Myiasis

    PubMed Central

    Aich, Arindom; Al-Ismaili, Suad; Ramadhan, Fatma A.; Al-Wardi, Talal H. M.; Al-Salmi, Quasem; Al-Hashami, Hilal

    2015-01-01

    Pulmonary myiasis is an unusual form of myiasis in humans and has been recently identified as a cause of eosinophilic pneumonia. We report the case of a 13-year-old Omani boy who presented to the Royal Hospital, Muscat, Oman, in October 2014 with respiratory distress. Bronchial aspirates revealed features of eosinophilic pneumonia. Possible larvae identified in the cytology report, a high immunoglobulin E level and the patient history all indicated bronchial myiasis. The patient was treated with steroids and ventilation and has since been disease-free with no long-term side-effects. To the best of the authors knowledge, this is the first case of bronchial myiasis in Oman. PMID:26629385

  14. Diagnosis and management of eosinophilic esophagitis in children

    PubMed Central

    Teoh, Timothy; Chan, Edmond S.; Avinashi, Vishal; Ko, Hin Hin; Goldman, Ran D.

    2015-01-01

    Abstract Question After a few years of difficulty swallowing solids and feeling like food was getting stuck, a 13-year-old boy in my practice with peanut allergy and asthma was recently diagnosed with eosinophilic esophagitis (EoE). What is EoE and how is it diagnosed and managed? Answer Eosinophilic esophagitis is an immune-mediated disease resulting in inflammation of the esophagus. It is increasing in prevalence and incidence in countries like Canada, and frequently occurs in children with other allergic conditions. Unexplained feeding difficulties, vomiting, and solid-food dysphagia, especially in boys with atopy, supports the possibility of having EoE. A formal diagnosis is obtained by reviewing esophageal biopsies obtained through upper endoscopy performed while the patient is taking a proton pump inhibitor. Once EoE has been established, management should involve working collaboratively with gastroenterology and allergy specialists. Medical or dietary treatments are acceptable therapeutic approaches. PMID:26505065

  15. Eosinophilic Granulomatosis with Polyangiitis preceding allergic bronchopulmonary aspergillosis.

    PubMed

    Lee, W; Teo, F S W; Santosa, A; Teng, G G

    2015-11-01

    A 61-year-old Chinese man with long-standing, stable Eosinophilic Granulomatosis with Polyangiitis (EGPA) and asthma, presented with acute hypoxemia and declining obstructive pulmonary function. Elevated serum IgE levels, positive Aspergillus fumigatus specific IgE and CT findings of central bronchiectasis with small airway mucoid impaction confirmed new development of Allergic Bronchopulmonary Aspergillosis (ABPA). The maintenance therapy for EGPA, azathioprine, was discontinued. Prednisolone 0.5 mg/kg/day and Itraconazole improved his symptoms and IgE levels. To our knowledge, ABPA occurring in a patient with EGPA has not been reported. Differentiation of EGPA with asthmatic flare vs ABPA vs asthma with aspergillus hypersensitivity is discussed. Heightened Th2 immunity where eosinophils play a central role may link these conditions. PMID:26549342

  16. Postpartum onset and subsequent relapse of eosinophilic granulomatosis with polyangiitis.

    PubMed

    Edwards, Mark Hiley; Curtis, Elizabeth Mary; Ledingham, Joanna Mary

    2015-01-01

    Eosinophilic granulomatosis with polyangiitis (EGPA) can affect women of childbearing age. However, reports of the disease in the postpartum period are limited. We present a case of postpartum-onset EGPA that went into clinical remission before relapsing in the subsequent postpartum period. Our patient presented with dyspnoea, arthralgia and rash, shown to be eosinophilic vasculitis, 3 days following the birth of her second child. CT of the thorax showed alveolar shadowing and mediastinal lymphadenopathy. She was treated successfully for EGPA with glucocorticoid therapy. She declined maintenance treatment during remission. Off treatment, she remained disease free throughout her next pregnancy. In the postpartum period she relapsed in an almost identical manner, requiring prolonged glucocorticoid therapy, cyclophosphamide and rituximab. This case highlights the importance of maintenance therapy around pregnancy in individuals with EGPA, and the need for careful monitoring of women with a history of EGPA in the postpartum period. PMID:26106182

  17. A rare cause of chronic dysphagia: eosinophilic esophagitis

    PubMed Central

    Destek, Sebahattin; Gul, Vahit Onur; Ahioglu, Serkan; Tatar, Zeynep; Erbil, Yesim

    2014-01-01

    Eosinophilic esophagitis (EE) is attributable to environmental factors, allergens and several immunological causes. The most typical symptoms include dysphagia and sensation of food impingement in the retrosternal area. Although its clinical features resemble those of gastroesophageal reflux, proton pump inhibitors are not effective for its treatment. The diagnosis of EE is dependent on the pathological detection of eosinophilic infiltration in esophageal mucosa. In this study, we evaluated a patient who applied to our clinic with complaints of long-term difficulty in swallowing, sensation of food sticking while eating and weight loss; the patient was diagnosed with EE, following biochemical, radiological, endoscopic and pathological assessments and was treated with steroids. The results show that EE should be considered in the differential diagnosis of patients with dysphagia and food impingement in the retrosternal area, and the diagnosis should be confirmed through multiple esophageal biopsies. PMID:25249002

  18. [Differencial diagnosis of gastroesophageal reflux disease -- eosinophilic esophagitis: case report].

    PubMed

    Franzius, M; Stolte, M; Porschen, R

    2005-04-01

    We report on a 22-year-old man with dysphagia and repeated bolus impaction in the esophagus for 10 years. Bolus impactions were frequently mobilised using an endoscope. At endoscopy, esophagitis IV degrees was described. After treatment with omeprazol there was no improvement. The patient was submitted to our hospital for fundoplication. pH-metry demonstrated an increased reflux. At endoscopy of the esophagus, we found red stripes which did not show the typical appearance of erosions. Manometry and X-ray films of the esophagus did not reveal any pathological findings. In combination with anamnesis, symptoms, and endoscopy, the diagnosis of eosinophilic esophagitis was documented by histology. After administration of oral corticosteroids a rapid improvement of the clinical symptoms was observed. The diagnosis of eosinophilic esophagitis should be kept in mind in patients with chronic symptoms of gastroesophageal reflux persisting despite medical therapy, pathological pH-metry and repeated bolus impactions. PMID:15830305

  19. Eosinophilic Esophagitis: The "Not-So-Rare" Disease.

    PubMed

    Goh, Vi Lier

    2016-02-01

    Eosinophilic esophagitis (EoE) is a relatively newly described disorder with increasing incidence. Patients with EoE may present at all ages from childhood through adulthood. Presenting symptoms may vary from feeding refusal, gagging, and/or vomiting in the younger population, dysphagia, chest pain, and abdominal pain in adolescents, as well as emergent food impactions. However, there are strict diagnostic criteria that must be met to make the diagnosis. Specifically, the diagnosis of EoE requires at least 15 eosinophils per high-powered field in the esophageal biopsies and symptoms of esophageal dysfunction after other causes, such as gastroesophageal reflux disease and proton pump inhibitor-responsive esophageal eosinophilia, have been ruled out. Common treatments include diet modifications and/or topical corticosteroids. [Pediatr Ann. 2016;45(2):e63-e66.]. PMID:26878186

  20. Eosinophilic Otitis Media: CT and MRI Findings and Literature Review

    PubMed Central

    Chung, Won Jung; Lim, Hyun Kyung; Yoon, Tae Hyun; Cho, Kyung Ja; Baek, Jung Hwan

    2012-01-01

    Eosinophilic otitis media (EOM) is a relatively rare, intractable, middle ear disease with extremely viscous mucoid effusion containing eosinophils. EOM is associated with adult bronchial asthma and nasal allergies. Conventional treatments for otitis media with effusion (OME) or for chronic otitis media (COM), like tympanoplasty or mastoidectomy, when performed for the treatment of EOM, can induce severe complications such as deafness. Therefore, it should be differentiated from the usual type of OME or COM. To our knowledge, the clinical and imaging findings of EOM of temporal bone are not well-known to radiologists. We report here the CT and MRI findings of two EOM cases and review the clinical and histopathologic findings of this recently described disease entity. PMID:22563277

  1. HOX Proteins and Leukemia

    PubMed Central

    Sitwala, Kajal V.; Dandekar, Monisha N.; Hess, Jay L.

    2008-01-01

    HOX and three amino acid loop extension (TALE) proteins cooperate to induce transformation in mouse leukemia models, and are dysregulated in a variety of human leukemias. Despite decades of research, the mechanism of action for Hox proteins in embryogenesis and hematopoiesis remains unclear. Recent studies on the roles of Hoxa9 and Meis1 in leukemia has led to a wealth of new data, but their molecular mechanisms of action and synergy remain obscure. Advances in genome-wide technologies offer new avenues for understanding how homeodomain-containing transcription factors exert their programs in normal and neoplastic development. PMID:18787682

  2. Evaluation of the Effectiveness of Antibiotics against Eosinophilic Pustular Folliculitis

    PubMed Central

    Ono, Sachiko; Yamamoto, Yosuke; Otsuka, Atsushi; Kabashima, Kenji; Miyachi, Yoshiki

    2013-01-01

    Eosinophilic pustular folliculitis (EPF) is a chronic intractable pruritic dermatosis. Although indomethacin is generally effective against EPF and considered as a first-line therapy, quite a few patients with indomethacin still suffer from the symptoms. Among other therapeutic options, some antibiotics have been reported to be effective; however, there has been no epidemiological description regarding oral antibiotics use in patients with EPF. In this study, we investigated the frequency of antibiotics use and the effectiveness in patients with EPF. PMID:23741214

  3. What Is Acute Lymphocytic Leukemia (ALL)?

    MedlinePLUS

    ... key statistics about acute lymphocytic leukemia? What is acute lymphocytic leukemia? Cancer starts when cells in the body begin ... leukemias). The rest of this document focuses on acute lymphocytic leukemia (ALL) in adults. For information on ALL in ...

  4. How Is Acute Lymphocytic Leukemia Found?

    MedlinePLUS

    ... How is acute lymphocytic leukemia classified? How is acute lymphocytic leukemia found? At this time there are no special ... oncologist (doctor who treats cancer). Tests to find acute lymphocytic leukemia Most of the symptoms seen in leukemia can ...

  5. Clinical Implications and Pathogenesis of Esophageal Remodeling in Eosinophilic Esophagitis

    PubMed Central

    Hirano, Ikuo; Aceves, Seema S.

    2014-01-01

    In eosinophilic esophagitis (EoE), remodeling changes are manifest histologically in both the epithelium as well as in the subepithelium where lamina propria (LP) fibrosis, expansion of the muscularis propria and increased vascularity occur. The major clinical symptoms and complications of EoE are largely consequences of esophageal remodeling. Important mediators of the process include IL-5, IL-13, TGF?1, mast cells, fibroblasts and eosinophils. Methods to detect remodeling effects include upper endoscopy, histopathology, barium esophagram, endoscopic ultrasonography, esophageal manometry, and functional luminal imaging. These modalities provide evidence of organ dysfunction that include focal and diffuse esophageal strictures, expansion of the mucosa and subepithelium, esophageal motor abnormalities and reduced esophageal distensibility. Complications of food impaction and perforations of the esophageal wall have been associated with reduction in esophageal caliber and increased esophageal mural stiffness. The therapeutic benefits of topical corticosteroids and elimination diet therapy in resolving mucosal eosinophilic inflammation of the esophagus are evident. Available therapies, however, have demonstrated variable ability to reverse existing remodeling changes of the esophagus. Systemic therapies that include novel, targeted biologic agents have the potential of addressing subepithelial remodeling. Esophageal dilation remains a useful, adjunctive therapeutic maneuver in symptomatic adults with esophageal stricture. As novel treatments emerge, it is essential that therapeutic endpoints account for the fundamental contributions of esophageal remodeling to overall disease activity. PMID:24813517

  6. Nasal histamine responses in nonallergic rhinitis with eosinophilic syndrome

    PubMed Central

    Ciofalo, Andrea; Romeo, Raffaello; Soldo, Pietro; Fusconi, Massimo; Greco, Antonio; Magliulo, Giuseppe; de Vincentiis, Marco

    2015-01-01

    Background: Nonallergic rhinitis with eosinophilic syndrome (NARES) is persistent, without atopy, but with 25% nasal eosinophilia. Hypereosinophilia seems to contribute to nasal mucosa dysfunction. Objectives: This analytical case-control study aimed at assessing the presence and severity of nonspecific nasal hyperactivity and at finding out whether eosinophilia may be correlated with the respiratory and mucociliary clearance functions. Materials: The symptom score was assessed in 38 patients and 15 controls whose nasal smear was also tested for eosinophils and mucociliary transport (MCT). Nonspecific nasal provocation tests (NSNPT) with histamine were also carried out, and total nasal resistance (TNR) was determined. Results: The symptom score of NARES after NSNPT were not significantly different from the control group, and there was poor or no correlation among the single symptoms and the differences studied for every nasal reactivity class. This correlation improved when using the composite symptom score. The most severe eosinophilia was observed in high reactivity groups, and it was correlated with an increase in TNR. MCT worsened as eosinophilia and nasal reactivity increased. Unlike controls, a significant correlation was observed between the increase in MCT and TNR. Conclusions: In NARES, nonspecific nasal hyperreactivity is the result of epithelial damage produced by eosinophilic inflammation, which causes MCT slow down, an increase in TNR, and nasal reactivity classes, with possible impact on classification, prognosis, and treatment control. PMID:26302729

  7. Eosinophils in Fungus-Associated Allergic Pulmonary Disease

    PubMed Central

    Ghosh, Sumit; Hoselton, Scott A.; Dorsam, Glenn P.; Schuh, Jane M.

    2013-01-01

    Asthma is frequently caused and/or exacerbated by sensitization to fungal allergens, which are ubiquitous in many indoor and outdoor environments. Severe asthma with fungal sensitization is characterized by airway hyperresponsiveness and bronchial constriction in response to an inhaled allergen that is worsened by environmental exposure to airborne fungi and which leads to a disease course that is often very difficult to treat with standard asthma therapies. As a result of complex interactions among inflammatory cells, structural cells, and the intercellular matrix of the allergic lung, patients with sensitization to fungal allergens may experience a greater degree of airway wall remodeling and progressive, accumulated pulmonary dysfunction as part of the disease sequela. From their development in the bone marrow to their recruitment to the lung via chemokine and cytokine networks, eosinophils form an important component of the inflammatory milieu that is associated with this syndrome. Eosinophils are recognized as complex multi-factorial leukocytes with diverse functions in the context of allergic fungal asthma. In this review, we will consider recent advances in our understanding of the molecular mechanisms that are associated with eosinophil development and migration to the allergic lung in response to fungal inhalation, along with the eosinophils function in the immune response to and the immunopathology attributed to fungus-associated allergic pulmonary disease. PMID:23378838

  8. [Eosinophilic fasciitis (Shulman's disease): Diagnostic and therapeutic review].

    PubMed

    S鋝e, D

    2015-11-01

    Eosinophilic fasciitis (EF) is a rare connective tissue disease characterized by symmetrical and painful swelling with a progressive induration and thickening of the skin and soft tissues. The diagnosis of EF is often based on the association of characteristic skin or subcutaneous abnormalities and a thickened fascia with an inflammatory infiltration, mostly composed of lymphocytes and eosinophils. A peripheral eosinophilia is frequently present (60-90%) but is not mandatory for the EF diagnosis. At the onset, the morphological diagnosis might be helped by a muscle magnetic resonance imaging, which typically may evidence an increased signal intensity within the fascia and marked fascia enhancement after gadolinium administration at the acute phase of the disease. Differential diagnoses include eosinophilia-myalgia syndrome after L-tryprophane ingestion, hypereosinophilic syndromes (HES), systemic sclerosis, eosinophilic granulomatosis with polyangeitis, and peripheral T cell lymphomas with cutaneous involvement. There is no consensual therapeutic strategy. However, oral corticosteroids, with or without methylprednisolone pluses, remain the mainstay treatment with a significant improvement for the majority of patients. It might be associated to an immunosuppressive drug, mainly methotrexate, in patients with morphea-like lesions or an unsatisfactory response to corticosteroids alone. PMID:26385125

  9. Disease associations in eosinophilic oesophagitis and oesophageal eosinophilia.

    PubMed

    Lucendo, Alfredo J

    2015-10-01

    Eosinophilic infiltration into oesophageal tissue, typical of eosinophilic oesophagitis (EoE), has been described in several other conditions, including infections, hypersensitivity, and other autoimmune disorders. Since its description, EoE has been associated with an increasing number of diseases also characterized by tissue infiltration, including eosinophilic gastroenteritis and Crohn's disease. While an association between EoE and coeliac disease was previously reported, it is not supported by recent research. In contrast, EoE seems to be common in patients with a history of congenital oesophageal atresia, leading to hypotheses linking both disorders. The prevalence of EoE has also been shown to be eight times higher in patients with connective tissue disorders (CTDs), which has led to the proposal of an EoE-CTD phenotype, although this requires further assessment. This paper reviews the evidence of EoE's associations with several disorders, defining the common bases from an epidemiological, clinical, molecular and genetic perspective whenever possible. PMID:26552775

  10. Eosinophilic Endomyocarditis: A Rare Case of Neonatal Mortality

    PubMed Central

    Pollock, Allison J.; Hitt, Stacy L.; Stier, Michael A.; Houser, Laura M.

    2015-01-01

    BackgroundEosinophilic endomyocarditis (EEM) is a rare diagnosis that is extremely uncommon in newborns. This case report aimed to present a case of neonatal mortality from acute cardiac failure due to EEM. CaseOur report presents a term male neonate with minor complications in the immediate postnatal course, who was discharged at 48 hours of life, but who developed unexpected respiratory distress, followed by cardiac arrest and death at 3 days of life. One day after discharge, the infant developed respiratory distress and cool skin, and then developed cardiac arrest at the pediatrician's office, undergoing resuscitation with intravenous fluid, cardiopulmonary resuscitation, epinephrine, atropine, and failed intubation. Autopsy revealed EEM, an inflammatory infiltrative process involving the endomyocardium. PathologyPathogenesis involves three stages: (1) myocarditis with an acute eosinophilic inflammatory infiltrate followed by (2) myocyte necrosis and eventually (3) fibrosis in the final stage of the disease. DiscussionThe cause of death was acute cardiac failure due to intense eosinophilic infiltration and degranulation with early subendocardial myocyte necrosis but before development of extensive myocyte necrosis. This case appears to be the youngest patient reported with EEM. PMID:26495174

  11. Eosinophil-Associated Gene Pathways but not Eosinophil Numbers are Differentially Regulated between Synchrotron Microbeam Radiation Treatment and Synchrotron Broad-Beam Treatment by 48 Hours Postirradiation.

    PubMed

    Ibahim, M J; Yang, Y; Crosbie, J C; Stevenson, A; Cann, L; Paiva, P; Rogers, P A

    2016-01-01

    Synchrotron microbeam radiation treatment (MRT) is a preclinical radiotherapy technique with considerable clinical promise, although some of the underlying radiobiology of MRT is still not well understood. In recently reported studies, it has been suggested that MRT elicits a different tumor immune profile compared to broad-beam treatment (BB). The aim of this study was to investigate the effects of synchrotron MRT and BB on eosinophil-associated gene pathways and eosinophil numbers within and around the tumor in the acute stage, 48 h postirradiation. Balb/C mice were inoculated with EMT6.5 mouse mammary tumors and irradiated with microbeam radiation (112 and 560 Gy) and broad-beam radiation (5 and 9 Gy) at equivalent doses determined from a previous in vitro study. After tumors were collected 24 and 48 h postirradiation, RNA was extracted and quantitative PCR performed to assess eosinophil-associated gene expression. Immunohistochemistry was performed to detect two known markers of eosinophils: eosinophil-associated ribonucleases (EARs) and eosinophil major basic protein (MBP). We identified five genes associated with eosinophil function and recruitment (Ear11, Ccl24, Ccl6, Ccl9 and Ccl11) and all of them, except Ccl11, were differentially regulated in synchrotron microbeam-irradiated tumors compared to broad-beam-irradiated tumors. However, immunohistochemical localization demonstrated no significant differences in the number of EAR- and MBP-positive eosinophils infiltrating the primary tumor after MRT compared to BB. In conclusion, our work demonstrates that the effects of MRT on eosinophil-related gene pathways are different from broad-beam radiation treatment at doses previously demonstrated to be equivalent in an in vitro study. However, a comparison of the microenvironments of tumors, which received MRT and BB, 48 h after exposure showed no difference between them with respect to eosinophil accumulation. These findings contribute to our understanding of the role of differential effects of MRT on the tumor immune response. PMID:26720800

  12. Chronic Myeloid Leukemia

    MedlinePLUS

    ... hard for blood to do its work. In chronic myeloid leukemia (CML), there are too many granulocytes, a type of white blood cell. Most people with CML have a gene mutation (change) called the Philadelphia ...

  13. 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.

  14. Acute lymphoblastic leukemia (ALL)

    MedlinePLUS

    ... be found for ALL. The following factors may play a role in the development of all types of leukemia: Certain chromosome problems Exposure to radiation, including x-rays before birth Past treatment with chemotherapy drugs ...

  15. Flavopiridol in Treating Patients With Chronic Lymphocytic Leukemia

    ClinicalTrials.gov

    2013-01-16

    B-cell Chronic Lymphocytic 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

  16. Leukemias in telephone linemen

    SciTech Connect

    Obrams, G.I.

    1988-01-01

    An epidemiologic case-control study was conducted to assess the risk of leukemia in telephone linemen. Linemen work in close proximity to power distribution lines mounted on poles shared between the electrical utilities and the telephone companies. They are exposed to the associated electromagnetic fields, which have been suggested as a cause of leukemia. All deaths from leukemia that occurred among active or retired telephone company employees between 9175 and 1980 were identified. Study cases included all 222 active or pensioned employees who worked at least two years for AT T, were identified through the AT T mortality data base, died of leukemia other than chronic lymphocytic leukemia in the six-year period 1975-1980, and did not have another underlying hematologic cancer. Specific cell types of leukemia were identified from death certificates and company medical records. Six hundred and eighty-seven controls were selected from the Bell System Personnel Data Base, matched to the cases by age, sex, company and year of hire.

  17. Thrombosis and acute leukemia.

    PubMed

    Crespo-Sol疄, Erick

    2012-04-01

    Thrombosis is a common complication in patients with acute leukemia. While the presence of central venous lines, concomitant steroids, the use of Escherichia coli asparaginase and hereditary thrombophilic abnormalities are known risk factors for thrombosis in children, information on the pathogenesis, risk factors, and clinical outcome of thrombosis in adult patients with acute lymphoid leukemia (ALL) or acute myeloid leukemia (AML) is still scarce. Expert consensus and guidelines regarding leukemia-specific risk factors, thrombosis prevention, and treatment strategies, as well as optimal type of central venous catheter in acute leukemia patients are required. It is likely that each subtype of acute leukemia represents a different setting for the development of thrombosis and the risk of bleeding. This is perhaps due to a combination of different disease-specific pathogenic mechanisms of thrombosis, including the type of chemotherapy protocol chosen, the underlying patients health, associated risk factors, as well as the biology of the disease itself. The risk of thrombosis may also vary according to ethnicity and prevalence of hereditary risk factors for thrombosis; thus, it is advisable for Latin American, Asian, and African countries to report on their specific patient population. PMID:22507812

  18. Eosinophils in the 1990s: new perspectives on their role in health and disease.

    PubMed Central

    Wardlaw, A. J.

    1994-01-01

    Eosinophils are characterized by their unique crystalloid granules that contain four basic proteins--MBP, ECP, EDN and EPO. The cell has many common features with neutrophils but, unlike that cell type, eosinophils utilize VLA-4/VCAM-1 as an adherence pathway and have a number of other receptors not shared by neutrophils. These include recognition units for IgE (distinct from CD23), and receptors for IL-5, IL-3 and RANTES. Following stimulation with a variety of agents, eosinophils preferentially elaborate LTC4 as the major 5-lipoxygenase product of arachidonic acid and produce substantial amounts of PAF. Of particular interest is the ability of eosinophils to synthesize a number of cytokines. Thus eosinophils have marked pro-inflammatory potential. There is now convincing evidence that eosinophilia is T-cell dependent. The Th2-type cell, which selectively secretes IL-5 and IL-4, seems particularly involved. IL-5, IL-3 and GM-CSF are required for eosinophil maturation, and cause activation and prolonged survival of the mature cell. IL-5 is unique in that it promotes terminal differentiation of the committed eosinophil precursor and in vivo in mice appears to be sufficient on its own for eosinophil growth from uncommited stem cells. IL-4 selectively upregulates VCAM-1 expression on endothelial cells thus augmenting VLA-4-dependent eosinophil adhesion. The role of eosinophils in disease is complex but in general their numbers are increased in helminthic parasitic disease and atopic allergy and asthma. Eosinophil products can produce many of the pathological features of asthma, and helminthic larvae coated with immunoglobulin or complement are particularly susceptible to eosinophil-mediated cytotoxicity. Eosinopenia is often related to acute inflammation or stress. PMID:7937446

  19. [Acute myocardial infarction as Eosinophilic granulomatosis with polyangiitis (formerly Churg Strauss syndrome) initial presentation].

    PubMed

    Sulaiman, Wahinuddin; Seung, Ong Ping; Noor, Sabariah Mohd

    2014-01-01

    Eosinophilic granulomatosis with polyangiitis is a rare primary vasculitic disease characterized by hypereosinophilia, late onset asthma and extravascular eosinophil granulomas. We report a case presented initially with acute myocardial infarction which later only proceed with asthma, skin manifestations and peripheral neuropathy. Laboratory parameters showed hypereosinohpilia with negative perinuclear pattern of antineutrophil cytoplasmic autoantibodies (p-ANCA). Skin biopsy showed leucocytoclastic vasculitis with eosinophilic infiltration while coronary angiography was normal. The patient's symptoms improved with IV methylprednisolone, pulse cyclophosphamide and azathioprine. PMID:25627304

  20. Organ-specific eosinophilic disorders of the skin, lung and gastrointestinal tract

    PubMed Central

    Simon, Dagmar; Wardlaw, Andrew; Rothenberg, Marc E.

    2010-01-01

    Eosinophils are multifunctional leukocytes that increase in various tissues in a variety of disorders. Locally, they can be involved in the initiation and propagation of diverse inflammatory responses. In this review, the clinical association of eosinophils with diseases of the skin, lung and gastrointestinal tract is summarized. An approach to determining the causal role of eosinophils in these diseases is presented. Recent findings concerning molecular diagnosis, etiology and treatment are discussed. PMID:20392477

  1. 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

  2. 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

  3. Eosinophils promote resolution of acute peritonitis by producing proresolving mediators in mice.

    PubMed

    Yamada, Tomohiro; Tani, Yukako; Nakanishi, Hiroki; Taguchi, Ryo; Arita, Makoto; Arai, Hiroyuki

    2011-02-01

    Acute inflammation in healthy individuals is self-limiting and has an active termination program. The mechanisms by which acute inflammation is resolved are of interest. In murine zymosan-induced peritonitis, we found that eosinophils are recruited to the inflamed loci during the resolution phase of acute inflammation. In vivo depletion of eosinophils caused a resolution deficit, namely impaired lymphatic drainage with reduced appearance of phagocytes carrying engulfed zymosan in the draining lymph node, and sustained numbers of polymorphonuclear leukocytes in inflamed tissues. Liquid chromatography-tandem mass spectrometry-based lipidomics of the resolving exudates revealed that locally activated eosinophils in the resolution phase produced proresolving mediators, including protectin D1 (PD1) from docosahexaenoic acid. The resolution deficit caused by eosinophil depletion was rescued by eosinophil restoration or the administration of PD1. Eosinophils deficient in 12/15-lipoxygenase could not rescue the resolution phenotype. The present results indicate that mouse eosinophils and eosinophil-derived lipid mediators, including PD1, have a role in promoting the resolution of acute inflammation, expanding the roles of eosinophils in host defense and resolution. PMID:20959515

  4. Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis.

    PubMed

    Griseri, Thibault; Arnold, Isabelle C; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, Brent S; Crocker, Paul R; Powrie, Fiona

    2015-07-21

    The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target. PMID:26200014

  5. Circulating Human Eosinophils Share a Similar Transcriptional Profile in Asthma and Other Hypereosinophilic Disorders

    PubMed Central

    Barnig, Cindy; Demb矇l矇, Doulaye; Paul, Nicod癡me; Poirot, Anh; Uring-Lambert, B矇atrice; Georgel, Philippe; de Blay, Fr矇deric; Bahram, Seiamak

    2015-01-01

    Eosinophils are leukocytes that are released into the peripheral blood in a phenotypically mature state and are capable of being recruited into tissues in response to appropriate stimuli. Eosinophils, traditionally considered cytotoxic effector cells, are leukocytes recruited into the airways of asthma patients where they are believed to contribute to the development of many features of the disease. This perception, however, has been challenged by recent findings suggesting that eosinophils have also immunomodulatory functions and may be involved in tissue homeostasis and wound healing. Here we describe a transcriptome-based approachin a limited number of patients and controlsto investigate the activation state of circulating human eosinophils isolated by flow cytometry. We provide an overview of the global expression pattern in eosinophils in various relevant conditions, e.g., eosinophilic asthma, hypereosinophilic dermatological diseases, parasitosis and pulmonary aspergillosis. Compared to healthy subjects, circulating eosinophils isolated from asthma patients differed in their gene expression profile which is marked by downregulation of transcripts involved in antigen presentation, pathogen recognition and mucosal innate immunity, whereas up-regulated genes were involved in response to non-specific stimulation, wounding and maintenance of homeostasis. Eosinophils from other hypereosinophilic disorders displayed a very similar transcriptional profile. Taken together, these observations seem to indicate that eosinophils exhibit non-specific immunomodulatory functions important for tissue repair and homeostasis and suggest new roles for these cells in asthma immunobiology. PMID:26524763

  6. Bronchoalveolar lavage and technetium-99m glucoheptonate imaging in chronic eosinophilic pneumonia

    SciTech Connect

    Lieske, T.R.; Sunderrajan, E.V.; Passamonte, P.M.

    1984-02-01

    A patient with chronic eosinophilic pneumonia was evaluated using bronchoalveolar lavage, technetium-99m glucoheptonate, and transbronchial lung biopsy. Bronchoalveolar lavage revealed 43 percent eosinophils and correlated well with results of transbronchial lung biopsy. Technetium-99m glucoheptonate lung imaging demonstrated intense parenchymal uptake. After eight weeks of corticosteroid therapy, the bronchoalveolar lavage eosinophil population and the technetium-99m glucoheptonate uptake had returned to normal. We suggest that bronchoalveolar lavage, with transbronchial lung biopsy, is a less invasive way than open lung biopsy to diagnose chronic eosinophilic pneumonia. The mechanism of uptake of technetium-99m glucoheptonate in this disorder remains to be defined.

  7. Significance of Mouse Models in Dissecting the Mechanism of Human Eosinophilic Gastrointestinal Diseases (EGID)

    PubMed Central

    Mishra, Anil

    2015-01-01

    Evidence suggests that eosinophils play a significant role in promoting several gastrointestinal diseases, and animal models are the significant tools to understand the pathogenesis of eosinophil-associatd inflammatory disorders. The focus of this review is on the significance of mouse models that mimic the characteristics of human eosinophilic gastrointestinal diseases. Eosinophils are the important leukocytes with diverse functions in the gastrointestinal tract, such as excretion of intestinal parasites and promoting the pathogenesis of a numerous allergic gastrointestinal disorders like food allergy, parasitic infection, allergic gastroenteritis, allergic colitis, and eosinophilic esophagitis. Among these gastrointestinal diseases, the eosinophilic esophagitis is the most recently recognized disease and the mouse models are proven to be an effective tool to understand the pathophysiology of disease and to test novel treatment strategies. Based on patients allergic conditions and the gene overexpressed in human EGID, a number of gene overexpressed and allergen-challenged mouse models of gastrointestinal disorders were developed. These models were utilized to explore the mechanism(s) that promotes the eosinophil-mediated gastrointestinal diseases including the role of the eosinophil responsive cytokines and chemokines. Herein, we have provided a detailed overviews of the mouse models of gastrointestinal disorders that mimic the human eosinophilic gastrointestinal diseases and can be utilized as a tool for understanding the diseases pathogenesis and developing novel therapeutic targets. PMID:25866707

  8. Granulocyte Macrophage Colony-Stimulating Factor-Activated Eosinophils Promote Interleukin-23 Driven Chronic Colitis

    PubMed Central

    Griseri, Thibault; Arnold, IsabelleC.; Pearson, Claire; Krausgruber, Thomas; Schiering, Chris; Franchini, Fanny; Schulthess, Julie; McKenzie, BrentS.; Crocker, PaulR.; Powrie, Fiona

    2015-01-01

    Summary The role of intestinal eosinophils in immune homeostasis is enigmatic and the molecular signals that drive them from protective to tissue damaging are unknown. Most commonly associated with Th2 cell-mediated diseases, we describe a role for eosinophils as crucial effectors of the interleukin-23 (IL-23)-granulocyte macrophage colony-stimulating factor (GM-CSF) axis in colitis. Chronic intestinal inflammation was characterized by increased bone marrow eosinopoiesis and accumulation of activated intestinal eosinophils. IL-5 blockade or eosinophil depletion ameliorated colitis, implicating eosinophils in disease pathogenesis. GM-CSF was a potent activator of eosinophil effector functions and intestinal accumulation, and GM-CSF blockade inhibited chronic colitis. By contrast neutrophil accumulation was GM-CSF independent and dispensable for colitis. In addition to TNF secretion, release of eosinophil peroxidase promoted colitis identifying direct tissue-toxic mechanisms. Thus, eosinophils are key perpetrators of chronic inflammation and tissue damage in IL-23-mediated immune diseases and it suggests the GM-CSF-eosinophil axis as an attractive therapeutic target. PMID:26200014

  9. Expression microarray analysis identifies novel epithelial-derived protein markers in eosinophilic esophagitis.

    PubMed

    Matoso, Andres; Mukkada, Vincent A; Lu, Shaolei; Monahan, Renee; Cleveland, Kelly; Noble, Lelia; Mangray, Shamlal; Resnick, Murray B

    2013-05-01

    Gene expression studies in eosinophilic esophagitis support an immune-mediated etiology associated with differential regulation of inflammatory and epithelial-derived genes. We aimed to further characterize epithelial gene expression alterations in eosinophilic esophagitis and to explore the use of immunohistochemistry to identify these alterations. Esophageal biopsies from pediatric patients with eosinophilic esophagitis before and after therapy with topical steroids (N=7) were screened by gene expression microarray and results were validated by RT-PCR. A larger group of eosinophilic esophagitis patients (N=42) was then used to evaluate protein expression by immunohistochemistry compared with reflux patients (N=15) and normal controls (N=17). Microarray and RT-PCR studies identified overexpression of ALOX15 and tumor necrosis factor alpha-induced factor 6 (TNFAIP6) and underexpression of filaggrin (FLG), SLURP1 and cysteine-rich secretory protein 3 (CRISP3) in eosinophilic esophagitis. Immunohistochemistry for ALOX15 was positive in 95% of eosinophilic esophagitis and negative in all controls, all eosinophilic esophagitis after therapy and all reflux biopsies (P<0.001). TNFAIP6 was positive in 88% of eosinophilic esophagitis samples versus 47% of controls, 29% of eosinophilic esophagitis after therapy and 40% of reflux samples (P=0.002). Overexpression of both ALOX15 and TNFAIP6 directly correlated with the degree of eosinophilic infiltration. FLG was positive in 88% of controls and 100% of reflux biopsies, but negative in all eosinophilic esophagitis samples, and its expression was regained in 86% of eosinophilic esophagitis after therapy patients (P<0.001). SLURP1 expression was positive in all controls and reflux samples, but only positive in 5% of eosinophilic esophagitis and was re-expressed to 100% positivity in eosinophilic esophagitis after therapy patients (P<0.001). The majority of controls (89%) and reflux biopsies (100%) were positive for CRISP3 while eosinophilic esophagitis before therapy were positive in 14% of samples (P<0.001) with partial recovery after treatment (43%, P=0.105). This study identified five epithelial-derived markers differentially expressed in eosinophilic esophagitis easily detectable by immunohistochemistry with potential diagnostic utility. PMID:23503644

  10. Dyspnea and Wheezing after Adenosine Injection in a Patient with Eosinophilic Bronchitis

    PubMed Central

    Cartin-Ceba, Rodrigo; Aubry, Marie Christine; Lim, Kaiser

    2009-01-01

    A 58-year-old nonsmoker female was referred for evaluation of chronic cough of 13 months duration. After an initial work-up, the patient was diagnosed to have chronic cough due to eosinophilic bronchitis. The diagnostic work-up for eosinophilic bronchitis and bronchial biopsy is discussed. Eosinophilic bronchitis is differentiated from asthma. In addition, the patient developed dyspnea, flushing, and wheezing after the administration of adenosine during a cardiac stress test in spite of a negative methacholine challenge. This indirect stimulus of airway hyperresponsiveness suggests the possible involvement of mast cells in eosinophilic bronchitis. PMID:19902011

  11. Biomarkers of Eosinophil Involvement in Allergic and Eosinophilic Diseases: review of phenotypic and serum markers including a novel assay to quantify levels of soluble Siglec-8

    PubMed Central

    Na, Ho Jeong; Hamilton, Robert G.; Klion, Amy D.

    2012-01-01

    There remains considerable controversy in the management of eosinophilic disorders, mainly due to a paucity of information regarding the clinical interpretation of total blood eosinophil counts versus surface activation markers versus eosinophil-derived or eosinophil-influencing mediator levels. Regrettably, few tests have been validated that define a unique clinical or prognostic phenotype that is more useful than simply monitoring total blood eosinophil counts. In this manuscript, phenotypic (cell surface) markers, along with serum and tissue-based markers that have been examined in the context of disease activity, are reviewed. We also report the development of a novel assay for detecting soluble Siglec-8 (sSiglec-8), a protein likely derived largely from eosinophils, as a potential serum biomarker. The assay consists of a competitive ELISA using a recombinant Siglec-8-Fc fusion protein. The goal of this preliminary study was to determine if sSiglec-8 is a useful biomarker that differentiates among patients with various eosinophil-associated diseases. In the final analysis, it is fair to say that further research is sorely needed to fully understand and validate the utility of various biomarkers, including sSiglec-8, before their use in clinical practice can be recommended with confidence. PMID:22683541

  12. What Is Chronic Myelomonocytic Leukemia?

    MedlinePLUS

    ... The most common type of granulocyte is the neutrophil ; which is crucial in fighting bacteria. Other types ... are basophils, and eosinophils. When the number of neutrophils in the blood is low, it is called ...

  13. 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.

  14. Eosinophil-Derived Neurotoxin (EDN/RNase 2) and the Mouse Eosinophil-Associated RNases (mEars): Expanding Roles in Promoting Host Defense

    PubMed Central

    Rosenberg, Helene F.

    2015-01-01

    The eosinophil-derived neurotoxin (EDN/RNase2) and its divergent orthologs, the mouse eosinophil-associated RNases (mEars), are prominent secretory proteins of eosinophilic leukocytes and are all members of the larger family of RNase A-type ribonucleases. While EDN has broad antiviral activity, targeting RNA viruses via mechanisms that may require enzymatic activity, more recent studies have elucidated how these RNases may generate host defense via roles in promoting leukocyte activation, maturation, and chemotaxis. This review provides an update on recent discoveries, and highlights the versatility of this family in promoting innate immunity. PMID:26184157

  15. Successful early diagnosis and treatment in a case of Toxocara canis-induced eosinophilic myocarditis with eosinophil-rich pericardial effusion.

    PubMed

    Sangen, Hideto; Tanabe, Jun; Takano, Hitoshi; Shimizu, Wataru

    2015-01-01

    Fulminant myocarditis can become fatal if left untreated. Treatments for most types of myocarditis, including mechanical support, are limited. However, immediate systemic corticosteroids are known to be effective against eosinophilic myocarditis; therefore, prompt diagnosis of this disease is crucial. Unfortunately, the standard diagnostic tool for myocarditis, endomyocardial biopsy, does not provide immediate histopathological findings. Thus, a rapid diagnostic tool for identifying types of myocarditis is urgently required. We report here the first case of Toxocara canis-induced eosinophilic fulminant myocarditis which was diagnosed based on eosinophil-rich pericardial effusion where the patient recovered with early corticosteroid therapy. PMID:26338242

  16. Re-defining the Unique Roles for Eosinophils in Allergic Respiratory Inflammation

    PubMed Central

    Jacobsen, Elizabeth A.; Lee, Nancy A.; Lee, James J.

    2014-01-01

    Summary The role of eosinophils in the progression and resolution of allergic respiratory inflammation is poorly defined despite the commonality of their presence and in some cases their use as a biomarker for disease severity and/or symptom control. However, this ambiguity belies the wealth of insights that have recently been gained through the use of eosinophil-deficient/attenuated strains of mice that have demonstrated novel immunoregulatory and remodeling/repair functions for these cells in the lung following allergen provocation. Specifically, studies of eosinophil-deficient mice suggest that eosinophils contribute to events occurring in the lungs following allergen provocation at several key moments: (i) The initiating phase of events leading to Th2-polarized pulmonary inflammation, (ii) The suppression Th1/Th17 pathways in lung draining lymph nodes, (iii) The recruitment of effector Th2 T cells to the lung, and finally (iv) Mechanisms of inflammatory resolution that re-establish pulmonary homeostasis. These suggested functions have recently been confirmed and expanded upon using allergen provocation of an inducible eosinophil-deficient strain of mice (iPHIL) that demonstrated an eosinophil-dependent mechanism(s) leading to Th2 dominated immune responses in the presence of eosinophils in contrast to neutrophilic as well as mixed Th1/Th17/Th2 variant phenotypes in the absence of eosinophils. These findings highlighted that eosinophils are not exclusively downstream mediators controlled by T cells, dendritic cells (DC), and/or innate lymphocytic cells (ILC2). Instead, eosinophils appear to be more aptly described as significant contributors in complex interrelated pathways that lead to pulmonary inflammation and subsequently promote resolution and the re-establishment of homeostatic baseline. In this review we summarize and put into the context the evolving hypotheses that are now expanding our understanding of the roles eosinophils likely have in the lung following allergen provocation. PMID:24961290

  17. COPD exacerbation severity and frequency is associated with impaired macrophage efferocytosis of eosinophils

    PubMed Central

    2014-01-01

    Background Eosinophilic airway inflammation is observed in 10-30% of COPD subjects. Whether increased eosinophils or impairment in their clearance by macrophages is associated with the severity and frequency of exacerbations is unknown. Methods We categorised 103 COPD subjects into 4 groups determined by the upper limit of normal for their cytoplasmic macrophage red hue (<6%), an indirect measure of macrophage efferocytosis of eosinophils, and area under the curve sputum eosinophil count (?3%/year). Eosinophil efferocytosis by monocyte-derived macrophages was studied in 17 COPD subjects and 8 normal controls. Results There were no differences in baseline lung function, health status or exacerbation frequency between the groups: A-low red hue, high sputum eosinophils (n?=?10), B-high red hue, high sputum eosinophils (n?=?16), C-low red hue, low sputum eosinophils (n?=?19) and D- high red hue, low sputum eosinophils (n?=?58). Positive bacterial culture was lower in groups A (10%) and B (6%) compared to C (44%) and D (21%) (p?=?0.01). The fall in FEV1 from stable to exacerbation was greatest in group A (?FEV1 [95 % CI] -0.41L [-0.65 to -0.17]) versus group B (-0.16L [-0.32 to -0.011]), C (-0.11L [-0.23 to -0.002]) and D (-0.16L [-0.22 to -0.10]; p?=?0.02). Macrophage efferocytosis of eosinophils was impaired in COPD versus controls (86 [75 to 92]% versus 93 [88 to 96]%; p?=?0.028); was most marked in group A (71 [70 to 84]%; p?=?0.0295) and was inversely correlated with exacerbation frequency (r?=?-0.63; p?=?0.006). Conclusions Macrophage efferocytosis of eosinophils is impaired in COPD and is related to the severity and frequency of COPD exacerbations. PMID:25007795

  18. 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 IIactive 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

  19. Aggressive eosinophilic granulomatosis with polyangiitis and transverse sinus thrombosis.

    PubMed

    Ananth, Snegha; Sankaralingam, Rajeswari; Manoj, Manesh

    2016-01-01

    We report a case of a patient with eosinophilic granulomatosis with polyangiitis (EGPA, previously known as Churg-Strauss syndrome) who succumbed to respiratory failure complicated by sepsis, pneumonitis and transverse sinus thrombosis. In the absence of antineutrophilic cytoplasmic antibodies positivity, a clinical diagnosis was made based on The American College of Rheumatology-1990 criteria. Glucocorticoids, cyclophosphamide, rituximab and intravenous immunoglobulin were administered at different stages. The patient recovered momentarily after each cycle of treatment, but his vasculitis progressed and he eventually died. Cardiac or renal involvement, which is more commonly associated with an adverse outcome, was not present. PMID:26759439

  20. Chronic Cough and Eosinophilic Esophagitis: An Uncommon Association

    PubMed Central

    Orizio, Paolo; Cinquini, Massimo; Minetti, Stefano; Alberti, Daniele; Paolo, Camilla Di; Villanacci, Vincenzo; Torri, Fabio; Crispino, Paola; Facchetti, Susanna; Rizzini, Fabio Lodi; Bassotti, Gabrio; Tosoni, Cinzia

    2011-01-01

    An increasing number of children, usually with gastrointestinal symptoms, is diagnosed with eosinophilic esophagitis (EE), and a particular subset of these patients complains of airway manifestations. We present the case of a 2-year-old child with chronic dry cough in whom EE was found after a first diagnosis of gastroesophageal reflux disease (GERD) due to pathological 24-hour esophageal pH monitoring. Traditional allergologic tests were negative, while patch tests were diagnostic for cow's milk allergy. We discuss the intriguing relationship between GERD and EE and the use of patch test for the allergologic screening of patients. PMID:21960955

  1. Eosinophilic cellulitis (Wells syndrome) caused by a temporary henna tattoo

    PubMed Central

    Celegen, Mehmet; Kark覺ner, Canan Sule Unsal; G羹nay, Ilker; Diniz, G羹llden; Can, Demet

    2014-01-01

    Eosinophilic cellulitis (Wells syndrome) is an uncommon condition of unknown etiology. Wells syndrome is usually seen in adulthood but very rare in childhood. Although pathogenesis of the disease is not very clear, it is a hypersensitivity reaction developing against a variety of exogenous and endogenous antigenic stimuli. Paraphenylenediamine is a strong allergen frequently used as a temporary henna tattoo, which makes the color darker. Here, a 9-year-old male patient with Wells syndrome is presented, which developed following a temporary henna tattoo and shown by the patch test sensitivity to paraphenylenediamine. PMID:25395929

  2. Current Diagnostic and Therapeutic Aspects of Eosinophilic Myocarditis

    PubMed Central

    Kuchynka, Petr; Palecek, Tomas; Masek, Martin; Cerny, Vladimir; Lambert, Lukas; Vitkova, Ivana; Linhart, Ales

    2016-01-01

    Eosinophilic myocarditis (EM) represents a rare form of myocardial inflammation with very heterogeneous aetiology. In developed countries, the most prevalent causes of EM are hypersensitivity or allergic reactions, as well as hematological diseases leading to eosinophilia. The disease may have a variable clinical presentation, ranging from asymptomatic forms to life-threatening conditions. Most patients with EM have marked eosinophilia in peripheral blood. Endomyocardial biopsy needs to be performed in most cases in order to establish a definitive diagnosis of EM. The therapy depends on the underlying aetiology. Immunosuppressive therapy represents the treatment mainstay in the majority of EM forms. PMID:26885504

  3. 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

  4. Eosinophil Infiltration of Solid Tumors Is an Early and Persistent Inflammatory Host Response

    PubMed Central

    Cormier, Stephania A.; Taranova, Anna G.; Bedient, Carrie; Nguyen, Thanh; Protheroe, Cheryl; Pero, Ralph; Dimina, Dawn; Ochkur, Sergei I.; ONeill, Katie; Colbert, Dana; Lombari, Theresa R.; Constant, Stephanie; McGarry, Michael P.; Lee, James J.; Lee, Nancy A.

    2012-01-01

    Tumor-associated eosinophilia has been observed in numerous human cancers and several tumor models in animals, however, the details surrounding this eosinophilia remain largely undefined and anecdotal. We used a B16-F10 melanoma cell injection model to demonstrate that eosinophil infiltration of tumors occurred from the earliest palpable stages with significant accumulations only in the necrotic and capsule regions. Furthermore, the presence of diffuse extracellular matrix staining for eosinophil major basic protein was restricted to the necrotic areas of tumors indicating that eosinophil degranulation was limited to this region. Antibody-mediated depletion of CD4+ T cells and adoptive transfer of eosinophils suggested, respectively, that the accumulation of eosinophils is not associated with Th2-dependent immune responses and that recruitment is a dynamic ongoing process, occurring throughout tumor growth. Ex vivo migration studies have identified what appears to be a novel chemotactic factor(s) released by stressed/dying melanoma cells, suggesting that the accumulation of eosinophils in tumors occurs, in part, through a unique mechanism dependent on a signal(s) released from areas of necrosis. Collectively, these studies demonstrate that the infiltration of tumors by eosinophils is an early and persistent response that is spatial restricted. More importantly, these data also show that the mechanism(s) that elicits this host response occurs independent of immune surveillance, suggesting that eosinophils are part of an early inflammatory reaction at the site of tumorigenesis. PMID:16617160

  5. Eosinophilic airway inflammation: role in asthma and chronic obstructive pulmonary disease

    PubMed Central

    George, Leena; Brightling, Christopher E.

    2016-01-01

    The chronic lung diseases, asthma and chronic obstructive pulmonary disease (COPD), are common affecting over 500 million people worldwide and causing substantial morbidity and mortality. Asthma is typically associated with Th2-mediated eosinophilic airway inflammation, in contrast to neutrophilic inflammation observed commonly in COPD. However, there is increasing evidence that the eosinophil might play an important role in 1040% of patients with COPD. Consistently in both asthma and COPD a sputum eosinophilia is associated with a good response to corticosteroid therapy and tailored strategies aimed to normalize sputum eosinophils reduce exacerbation frequency and severity. Advances in our understanding of the multistep paradigm of eosinophil recruitment to the airway, and the consequence of eosinophilic inflammation, has led to the development of new therapies to target these molecular pathways. In this article we discuss the mechanisms of eosinophilic trafficking, the tools to assess eosinophilic airway inflammation in asthma and COPD during stable disease and exacerbations and review current and novel anti-eosinophilic treatments. PMID:26770668

  6. Some enzymatic characteristics of eosinophil peroxidase from patients with eosinophilia and from healthy donors.

    PubMed Central

    Bos, A J; Wever, R; Hamers, M N; Roos, D

    1981-01-01

    Some enzymatic characteristics of human eosinophil peroxidase were compared with those of human myeloperoxidase. Both enzymes catalyzed the oxidation of iodide by hydrogen peroxide. This assay proved to be very sensitive; the activity of 100 eosinophils/ml could be measured. The position of the pH optimum of this reaction was linearly dependent on the logarithm of the iodide/H2O2 ratio. At the same substrate ratio, this optimum was about 1 pH unit higher for eosinophil peroxidase than for myeloperoxidase. This difference may be related to the action of myeloperoxidase inside an acidified phagolysosome as opposed to the extracellular action of eosinophil peroxidase on the surface of certain parasites. Under defined conditions (KI, 1.4 mM; H2O2, 0.18 mM; cetyltrimethylammonium bromide, 0.008% [wt/vol]; pH 6), the activity of eosinophil peroxidase could be measured in a mixed granulocyte suspension independently of myeloperoxidase. Eosinophils from patients with eosinophilia were found to contain as much peroxidase activity as did eosinophils from healthy donors. No enzymatic differences in eosinophil peroxidase were found between the two types of donors. PMID:6265355

  7. Molecular cloning and characterization of a human eotaxin receptor expressed selectively on eosinophils

    PubMed Central

    1996-01-01

    The chemokine eotaxin is unusual in that it appears to be a highly specific chemoattractant for eosinophils. Ligand-binding studies with radiolabeled eotaxin demonstrated a receptor on eosinophils distinct from the known chemokine receptors CKR-1 and -2. The distinct eotaxin binding site on human eosinophils also bound RANTES (regulated on activation T expressed and secreted) and monocyte chemotactic protein (MCP)3. We have now isolated a cDNA from eosinophils, termed CKR-3, with significant sequence similarity to other well characterized chemokine receptors. Cells transfected with CKR-3 cDNA bound radiolabeled eotaxin specifically and with high affinity, comparable to the binding affinity observed with eosinophils. This receptor also bound RANTES and MCP-3 with high affinity, but not other CC or CXC chemokines. Furthermore, receptor transfectants generated in a murine B cell lymphoma cell line migrated in transwell chemotaxis assays to eotaxin, RANTES, and MCP-3, but not to any other chemokines. A monoclonal antibody recognizing CKR-3 was used to show that eosinophils, but not other leukocyte types, expressed this receptor. This pattern of expression was confirmed by Northern blot with RNA from highly purified leukocyte subsets. The restricted expression of CKR-3 on eosinophils and the fidelity of eotaxin binding to CKR-3, provides a potential mechanism for the selective recruitment and migration of eosinophils within tissues. PMID:8676064

  8. Identification of eosinophils in lysed whole blood using side scatter and CD16 negativity.

    PubMed

    Gopinath, R; Nutman, T B

    1997-12-15

    The identification of eosinophils in lysed whole blood by flow cytometry can be problematic, since these cells overlap significantly with the neutrophil cluster on forward scatter versus side scatter plots of whole blood samples. Current methods can be time-consuming when running multiple samples or may compromise yield in the interests of greater accuracy. The use of eosinophil purification techniques prior to FACS analysis or sorting as a way of ensuring purity may have unpredictable effects on eosinophil activation, leading to questionable data interpretation. Here we describe a simple, single-step method for definition of eosinophils utilizing their high side scatter and CD16 fluorescence negativity to differentiate them from neutrophils. The purity of the neutrophil and eosinophil populations sorted with this gate is close to 100% regardless of the peripheral blood eosinophil count, while the population obtained by sorting on a plot of FSC/SSC was a mixture of eosinophils and neutrophils. We suggest this method as a simple, reproducible, and accurate way of defining eosinophils by flow cytometry for analysis or sorting. PMID:9440823

  9. IL-1? in eosinophil-mediated small intestinal homeostasis and IgA production

    PubMed Central

    Jung, Y; Wen, T; Mingler, MK; Caldwell, JM; Wang, YH; Chaplin, DD; Lee, EH; Jang, MH; Woo, SY; Seoh, JY; Miyasaka, M; Rothenberg, ME

    2014-01-01

    Eosinophils are multifunctional leukocytes that reside in the gastrointestinal (GI) lamina propria, where their basal function remains largely unexplored. In this study, by examining mice with a selective deficiency of systemic eosinophils (by lineage ablation) or GI eosinophils (eotaxin-1/2 doubledeficient or CC chemokine receptor 3deficient), we show that eosinophils support immunoglobulin A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal microbial composition, and promote the development of Peyers patches. Eosinophil-deficient mice showed reduced expression of mediators of secretory IgA production, including intestinal interleukin 1? (IL-1?), inducible nitric oxide synthase, lymphotoxin (LT) ?, and LT-?, and reduced levels of retinoic acid-related orphan receptor gamma tpositive (ROR-?t+) innate lymphoid cells (ILCs) while maintaining normal levels of APRIL (a proliferation-inducing ligand), BAFF (B cellactivating factor of the tumor necrosis factor family), and TGF-? (transforming growth factor ?). GI eosinophils expressed a relatively high level of IL-1?, and IL-1?deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA+ cells and ROR-?t+ ILCs. On the basis of these collective data, we propose that eosinophils are required for homeostatic intestinal immune responses including IgA production and that their affect is mediated via IL-1? in the small intestine. PMID:25563499

  10. IL-1? in eosinophil-mediated small intestinal homeostasis and IgA production.

    PubMed

    Jung, Y; Wen, T; Mingler, M K; Caldwell, J M; Wang, Y H; Chaplin, D D; Lee, E H; Jang, M H; Woo, S Y; Seoh, J Y; Miyasaka, M; Rothenberg, M E

    2015-07-01

    Eosinophils are multifunctional leukocytes that reside in the gastrointestinal (GI) lamina propria, where their basal function remains largely unexplored. In this study, by examining mice with a selective deficiency of systemic eosinophils (by lineage ablation) or GI eosinophils (eotaxin-1/2 double deficient or CC chemokine receptor 3 deficient), we show that eosinophils support immunoglobulin A (IgA) class switching, maintain intestinal mucus secretions, affect intestinal microbial composition, and promote the development of Peyer's patches. Eosinophil-deficient mice showed reduced expression of mediators of secretory IgA production, including intestinal interleukin 1? (IL-1?), inducible nitric oxide synthase, lymphotoxin (LT) ?, and LT-?, and reduced levels of retinoic acid-related orphan receptor gamma t-positive (ROR-?t(+)) innate lymphoid cells (ILCs), while maintaining normal levels of APRIL (a proliferation-inducing ligand), BAFF (B cell-activating factor of the tumor necrosis factor family), and TGF-? (transforming growth factor ?). GI eosinophils expressed a relatively high level of IL-1?, and IL-1?-deficient mice manifested the altered gene expression profiles observed in eosinophil-deficient mice and decreased levels of IgA(+) cells and ROR-?t(+) ILCs. On the basis of these collective data, we propose that eosinophils are required for homeostatic intestinal immune responses including IgA production and that their affect is mediated via IL-1? in the small intestine. PMID:25563499

  11. Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury

    PubMed Central

    Huang, Lu; Beiting, Daniel P.; Gebreselassie, Nebiat G.; Gagliardo, Lucille F.; Ruyechan, Maura C.; Lee, Nancy A.; Lee, James J.; Appleton, Judith A.

    2015-01-01

    It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth. PMID:26720604

  12. Eosinophils and IL-4 Support Nematode Growth Coincident with an Innate Response to Tissue Injury.

    PubMed

    Huang, Lu; Beiting, Daniel P; Gebreselassie, Nebiat G; Gagliardo, Lucille F; Ruyechan, Maura C; Lee, Nancy A; Lee, James J; Appleton, Judith A

    2015-12-01

    It has become increasingly clear that the functions of eosinophils extend beyond host defense and allergy to metabolism and tissue regeneration. These influences have strong potential to be relevant in worm infections in which eosinophils are prominent and parasites rely on the host for nutrients to support growth or reproduction. The aim of this study was to investigate the mechanism underlying the observation that eosinophils promote growth of Trichinella spiralis larvae in skeletal muscle. Our results indicate that IL-4 and eosinophils are necessary for normal larval growth and that eosinophils from IL-4 competent mice are sufficient to support growth. The eosinophil-mediated effect operates in the absence of adaptive immunity. Following invasion by newborn larvae, host gene expression in skeletal muscle was compatible with a regenerative response and a shift in the source of energy in infected tissue. The presence of eosinophils suppressed local inflammation while also influencing nutrient homeostasis in muscle. Redistribution of glucose transporter 4 (GLUT4) and phosphorylation of Akt were observed in nurse cells, consistent with enhancement of glucose uptake and glycogen storage by larvae that is known to occur. The data are consistent with a mechanism in which eosinophils promote larval growth by an IL-4 dependent mechanism that limits local interferon-driven responses that otherwise alter nutrient metabolism in infected muscle. Our findings document a novel interaction between parasite and host in which worms have evolved a strategy to co-opt an innate host cell response in a way that facilitates their growth. PMID:26720604

  13. Eosinophilic pleural effusion due to Spirometra mansoni spargana: a case report and review of the literature.

    PubMed

    Lin, Quan; Ouyang, Jin-Sheng; Li, Jian-Min; Yang, Li; Li, Yu-Ping; Chen, Cheng-Shui

    2015-05-01

    A 36-year-old female presented with an eosinophilic pleural effusion. The eosinophilic pleural effusion was considered to have been caused by a parasitic infection. Spirometra mansoni spargana was confirmed by semi-rigid thoracoscopy. About 2 months after treatment with praziquantel for 3 days, the pleural effusion had disappeared on the chest roentgenogram. PMID:25820094

  14. Hepatomegaly and Periportal Oedema of the Liver in a Patient with Eosinophilic Gastroenteritis

    PubMed Central

    HUI, Chee-Kin

    2013-01-01

    Periportal halos are an uncommon finding on computerised tomography (CT) of the liver. Here, reported a case of periportal halos and hepatomegaly in a patient with eosinophilic gastroenteritis. A 49-year-old male presented with a six week history of right lower quadrant pain and diarrhoea. A CT of the abdomen showed hepatomegaly and multiple hypodense periportal halos around the patent portal veins consistent with periportal oedema. A colonoscopy showed normal looking mucosa in the colon and terminal ileum. Blind biopsies taken throughout the terminal ileum and colon showed increased numbers of eosinophils (more than 25 per high-power field) consistent with eosinophilic gastroenteritis. A liver biopsy showed minimal non-specific chronic inflammatory infiltrates and eosinophils in the portal tracts with ductular proliferation. In conclusion, eosinophilic gastroenteritis should be considered in patients presenting with periportal halos, hepatomegaly, and diarrhoea. PMID:24643224

  15. Acute eosinophilic pneumonia in a New York City firefighter exposed to World Trade Center dust.

    PubMed

    Rom, William N; Weiden, Michael; Garcia, Roberto; Yie, Ting An; Vathesatogkit, Pratan; Tse, Doris B; McGuinness, Georgeann; Roggli, Victor; Prezant, David

    2002-09-15

    We report a sentinel case of acute eosinophilic pneumonia in a firefighter exposed to high concentrations of World Trade Center dust during the rescue effort from September 11 to 24. The firefighter presented with a Pa(O2) of 53 mm Hg and responded to oxygen and corticosteroids. Computed tomography scan showed patchy ground glass density, thickened bronchial walls, and bilateral pleural effusions. Bronchoalveolar lavage recovered 70% eosinophils, with only 1% eosinophils in peripheral blood. Eosinophils were not degranulated and increased levels of interleukin-5 were measured in bronchoalveolar lavage and serum. Mineralogic analysis counted 305 commercial asbestos fibers/10(6) macrophages including those with high aspect ratios, and significant quantities of fly ash and degraded fibrous glass. Acute eosinophilic pneumonia is a rare consequence of acute high dust exposure. World Trade Center dust consists of large particle-size silicates, but fly ash and asbestos fibers may be found in bronchoalveolar lavage cells. PMID:12231487

  16. Idiopathic eosinophilic pneumonia in children: the French experience

    PubMed Central

    2014-01-01

    Background Idiopathic eosinophilic pneumonia is extremely rare in children and adults. We present herein the first series describing the specificities of idiopathic chronic (ICEP) and acute (IAEP) eosinophilic pneumonia in children. Methods We retrospectively analyzed all cases of ICEP and IAEP in children that were retrieved from French Reference Centers for rare pediatric lung diseases. Results Five cases of pediatric ICEP were identified. Corticosteroid or immunosuppressive therapy dramatically improved the outcome in three cases. The remaining two cases had a persistent interstitial pattern with progressive development of cystic airspace lesions. Three cases of IAEP in adolescents were reported, with one requiring four days of extracorporeal membrane oxygenation. Conclusion ICEP is a rare disease with a polymorphic clinical presentation in children. We identified patients with persistent interstitial patterns progressing to cystic airspace regions, for which the boundaries with idiopathic interstitial pneumonias are difficult to establish. We therefore propose a specific pediatric definition and classification algorithm. IAEP in children remains an inflammatory reaction of the lung to an acute toxic exposure, mainly tobacco, as in adults. International studies are required to comprehensively assess the various clinical forms of the disease as well as the appropriate therapeutic regimens. PMID:24555756

  17. Perforated duodenal ulcer: An unusual manifestation of allergic eosinophilic gastroenteritis

    PubMed Central

    Riggle, Kevin M; Wahbeh, Ghassan; Williams, Elizabeth M; Riehle, Kimberly J

    2015-01-01

    Spontaneous perforation of a duodenal ulcer secondary to allergic eosinophilic gastroenteritis (EGE) has not been previously reported. We present such a case in a teenager who presented with peritonitis. After exploration and operative repair of his ulcer, he continued to experience intermittent abdominal pain, and further evaluation revealed eosinophilic gastroenteritis in the setting of multiple food allergies. His EGE resolved after adhering to a restrictive diet. Both duodenal ulcers and EGE are very rarely seen in pediatric patients. EGE has a variable presentation depending on the layer(s) of bowel wall affected and the segment of the gastrointestinal tract that is involved. Once diagnosed, it may respond to dietary changes in patients with recognized food allergies, or to steroids in patients in whom an underlying cause is not identified. Our case highlights the need to keep EGE in the differential diagnosis when treating pediatric patients with duodenal ulcers. The epidemiology, pathophysiology, and treatment of EGE are also discussed, along with a review of the current literature. PMID:26640348

  18. Eosinophilic CholangitisA Challenging Diagnosis of Benign Biliary Stricture

    PubMed Central

    Fragulidis, Georgios Panagiotis; Vezakis, Antonios I.; Kontis, Elissaios A.; Pantiora, Eirini V.; Stefanidis, Gerasimos G.; Politi, Aikaterini N.; Koutoulidis, Vasilios K.; Mela, Maria K.; Polydorou, Andreas A.

    2016-01-01

    Abstract When confronting a biliary stricture, both benign and malignant etiologies must be carefully considered as a variety of benign biliary strictures can masquerade as hilar cholangiocarcinoma (CCA). Therefore, patients could undergo a major surgery despite the possibility of a benign biliary disease. Approximately 15% to 24% of patients undergoing surgical resection for suspected biliary malignancy will have benign pathology. Eosinophilic cholangitis (EC) is a rare benign disorder of the biliary tract, which can cause obstructive jaundice and can pose a difficult diagnostic task. We present a rare case of a young woman who was referred to our hospital with obstructive painless jaundice due to a biliary stricture at the confluence of the hepatic bile ducts, with a provisional diagnosis of cholangiocarcinoma. Though, during her work up she was found to have EC, an extremely rare benign cause of biliary stricture, which is characterized by a dense eosinophilic infiltration of the biliary tree causing stricturing, fibrosis, and obstruction and which is reversible with short-term high-dose steroids. Despite its rarity, EC should be taken into consideration when imaging modalities demonstrate a biliary stricture, especially if preoperative diagnosis of malignancy cannot be made, in the setting of peripheral eosinophilia and the absence of cardinal symptoms of malignancy. PMID:26735539

  19. Immunotherapeutic approaches for the treatment of eosinophilic esophagitis

    PubMed Central

    Cianferoni, Antonella; Spergel, Jonathan M

    2015-01-01

    Eosinophilic esophagitis (EoE) is a clinical pathologic disease characterized by symptoms of esophageal dysfunction and eosinophilia of the esophagus. When the diagnosis is confirmed, it is important to treat the eosinophilic inflammation not only to control the presenting symptoms, but also to prevent acute and chronic complications. The pathogenesis of EoE is most likely a mixed IgE and non-IgE food-mediated reaction, where Th2 cytokines drive esophageal eosinophilia as in other atopic diseases. Hence, it is not surprising that therapy is based on inflammation control, with steroids (oral or topical) and/or food antigen avoidance. However, these treatment options are not specific, reduce the quality of life of patients and have significant side effects, therefore, there is an ongoing effort to design more specific immunotherapies. In this review, we review standard and immunotherapeutic options for EoE treatment, such as anti-IL-5, anti-TNF帢, anti-IgE, anti-CRTH, oral allergy desensitization and environmental immunotherapy. PMID:24762076

  20. Recent discoveries and emerging therapeutics in eosinophilic esophagitis

    PubMed Central

    Goyal, Aakash; Cheng, Edaire

    2016-01-01

    Eosinophilic esophagitis (EoE) is an allergy-mediated disease culminating in severe eosinophilic inflammation and dysfunction of the esophagus. This chronic disorder of the esophagus causes significant morbidity, poor quality of life, and complications involving fibrosis and esophageal remodeling. Overlapping features between EoE and gastroesophageal reflux disease (GERD) pose great challenges to differentiating the two conditions, although the two disorders are not mutually exclusive. Recent findings suggest that the confounding condition proton pump inhibitor - responsive esophageal eosinophilia (PPI-REE) is likely a subset of EoE. Since PPIs have therapeutic properties that can benefit EoE, PPIs should be considered as a therapeutic option for EoE rather than a diagnostic screen to differentiate GERD, PPI-REE, and EoE. Other current treatments include dietary therapy, corticosteroids, and dilation. Immunomodulators and biologic agents might have therapeutic value, and larger trials are needed to assess efficacy and safety. Understanding the pathophysiology of EoE is critical to the development of novel therapeutics. PMID:26855809

  1. Eosinophilic Esophagitis in Two Patients with Systemic Sclerosis

    PubMed Central

    Frech, Tracy M.; Boynton, Kathleen; Downs-Kelly, Erinn; Jones, Bryan; Kriesel, John D.; Peterson, Kathryn

    2016-01-01

    The gastrointestinal tract (GIT) is the most common extracutaneous organ system damaged in systemic sclerosis (SSc) and is the presenting feature in 10% of patients. The esophagus as the portion of the GIT is the most commonly affected and there is an association of gastroesophageal reflux (GER) with SSc interstitial lung disease (ILD). Thus, an aggressive treatment for GER is recommended in all SSc patients with ILD; however, it is recognized that a long-term benefit to this treatment is needed to understand its impact. In this case report we discuss the presence of eosinophilic esophagitis (EoE) in two SSc patients and discuss the role for early EGD in SSc patients with moderate-severe GER symptoms for tissue study. Assessment of esophageal biopsy specimens for the presence of eosinophils and possibly ANA can help elucidate disease pathogenesis and direct therapy, as the presence of EoE in SSc has important management considerations, particularly with regards to dietary modification strategies. PMID:26904346

  2. Update on Eosinophilic Meningoencephalitis and Its Clinical Relevance

    PubMed Central

    Graeff-Teixeira, Carlos; da Silva, Ana Cristina Ar嫥buru; Yoshimura, Kentaro

    2009-01-01

    Summary: Eosinophilic meningoencephalitis is caused by a variety of helminthic infections. These worm-specific infections are named after the causative worm genera, the most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Worm parasites enter an organism through ingestion of contaminated water or an intermediate host and can eventually affect the central nervous system (CNS). These infections are potentially serious events leading to sequelae or death, and diagnosis depends on currently limited molecular methods. Identification of parasites in fluids and tissues is rarely possible, while images and clinical examinations do not lead to a definitive diagnosis. Treatment usually requires the concomitant administration of corticoids and anthelminthic drugs, yet new compounds and their extensive and detailed clinical evaluation are much needed. Eosinophilia in fluids may be detected in other infectious and noninfectious conditions, such as neoplastic disease, drug use, and prosthesis reactions. Thus, distinctive identification of eosinophils in fluids is a necessary component in the etiologic diagnosis of CNS infections. PMID:19366917

  3. [Acantholysis and eosinophilic spongiosis: pemphigus herpetiformis. Successful retinoid therapy].

    PubMed

    Bauer, R; Stadler, R; Immel, C; Orfanos, C E

    1983-01-01

    Pemphigus herpetiformis is an unusual variant of the pemphigus group, showing acantholytic bulla formation together with marked eosinophilic spongiosis. The clinical picture shows erythematous and pruritic papulovesicular bullous lesions affecting the skin and the oral mucosa. It most closely resembles dermatitis herpetiformis or bullous pemphigoid. In contrast, the presence of acantholysis and of antiepithelial antibodies indicate pemphigus. Three patients, all women, showing this unusual variant of pemphigus, were seen during the last 3 years, a fourth is reported here. One patient responded well to dapsone; the three others did not. Oral treatment with aromatic retinoid (Ro 10-9359) was clearly effective in the last patient, leading to full remission of the skin lesions in a few days. The oral mucosa improved only partly. Discontinuation of the aromatic retinoid treatment and replacement of the drug by placebo was followed by a relapse both of mucosal and skin lesions. Aromatic retinoid possibly inhibits eosinophilic migration into the epidermis and impedes acantholysis associated with this phenomenon. PMID:6841074

  4. Elimination diets in the management of eosinophilic esophagitis

    PubMed Central

    Wechsler, Joshua B; Schwartz, Sally; Amsden, Katie; Kagalwalla, Amir F

    2014-01-01

    Eosinophilic esophagitis, an increasingly recognized chronic inflammatory disorder isolated to the esophagus, is triggered by an abnormal allergic response to dietary antigens. Current treatment includes swallowed topical steroids and dietary modification, which aim to resolve symptoms and prevent long-term complications such as formation of strictures. The dietary approach has become more widely accepted because long-term steroid therapy is associated with potential risks. Dietary treatment includes elemental and elimination diets. An exclusive elemental diet, which requires replacement of all intact protein with amino acid-based formula, offers the best response of all available therapies, with remission in up to 96% of subjects proving it to be superior to all other available therapies including topical steroids. However, compliance with this approach is challenging because of poor taste and monotony. The high cost of formula and the associated psychosocial problems are additional drawbacks of this approach. Empiric and allergy test-directed elimination diets have gained popularity given that elimination of a limited number of foods is much easier and as such is more readily acceptable. There is a growing body of literature supporting this type of therapy in both children and adults. This paper reviews the evidence for all types of dietary therapy in eosinophilic esophagitis. PMID:24920928

  5. Recent discoveries and emerging therapeutics in eosinophilic esophagitis.

    PubMed

    Goyal, Aakash; Cheng, Edaire

    2016-02-01

    Eosinophilic esophagitis (EoE) is an allergy-mediated disease culminating in severe eosinophilic inflammation and dysfunction of the esophagus. This chronic disorder of the esophagus causes significant morbidity, poor quality of life, and complications involving fibrosis and esophageal remodeling. Overlapping features between EoE and gastroesophageal reflux disease (GERD) pose great challenges to differentiating the two conditions, although the two disorders are not mutually exclusive. Recent findings suggest that the confounding condition proton pump inhibitor - responsive esophageal eosinophilia (PPI-REE) is likely a subset of EoE. Since PPIs have therapeutic properties that can benefit EoE, PPIs should be considered as a therapeutic option for EoE rather than a diagnostic screen to differentiate GERD, PPI-REE, and EoE. Other current treatments include dietary therapy, corticosteroids, and dilation. Immunomodulators and biologic agents might have therapeutic value, and larger trials are needed to assess efficacy and safety. Understanding the pathophysiology of EoE is critical to the development of novel therapeutics. PMID:26855809

  6. The Role and Immunobiology of Eosinophils in the Respiratory System: a Comprehensive Review.

    PubMed

    Eng, Stephanie S; DeFelice, Magee L

    2016-04-01

    The eosinophil is a fully delineated granulocyte that disseminates throughout the bloodstream to end-organs after complete maturation in the bone marrow. While the presence of eosinophils is not uncommon even in healthy individuals, these granulocytes play a central role in inflammation and allergic processes. Normally appearing in smaller numbers, higher levels of eosinophils in the peripheral blood or certain tissues typically signal a pathologic process. Eosinophils confer a beneficial effect on the host by enhancing immunity against molds and viruses. However, tissue-specific elevation of eosinophils, particularly in the respiratory system, can cause a variety of short-term symptoms and may lead to long-term sequelae. Eosinophils often play a role in more commonly encountered disease processes, such as asthma and allergic responses in the upper respiratory tract. They are also integral in the pathology of less common diseases including eosinophilic pneumonia, allergic bronchopulmonary aspergillosis, hypersensitivity pneumonitis, and drug reaction with eosinophilia and systemic symptoms. They can be seen in neoplastic disorders or occupational exposuresas well. The involvement of eosinophils in pulmonary disease processes can affect the method of diagnosis and the selection of treatment modalities. By analyzing the complex interaction between the eosinophil and its environment, which includes signaling molecules and tissues, different therapies have been discovered and created in order to target disease processes at a cellular level. Innovative treatments such as mepolizumab and benralizumab will be discussed. The purpose of this article is to further explore the topic of eosinophilic presence, activity, and pathology in the respiratory tract, as well as discuss current and future treatment options through a detailed literature review. PMID:26797962

  7. Association of the EGF-TM7 receptor CD97 expression with FLT3-ITD in acute myeloid leukemia

    PubMed Central

    Wobus, Manja; Bornh瓣user, Martin; Jacobi, Angela; Kr瓣ter, Martin; Otto, Oliver; Ortlepp, Claudia; Guck, Jochen; Ehninger, Gerhard; Thiede, Christian; Oelschl瓣gel, Uta

    2015-01-01

    Internal tandem duplications within the juxtamembrane region of the FMS-like tyrosine kinase receptor FLT3 (FLT3-ITD) represents one of the most common mutations in patients with acute myeloid leukemia (AML) which results in constitutive aberrant activation, increased proliferation of leukemic progenitors and is associated with an aggressive clinical phenotype. The expression of CD97, an EGF-TM7 receptor, has been linked to invasive behavior in thyroid and colorectal cancer. Here, we have investigated the association of CD97 with FLT3-ITD and its functional consequences in AML. Higher CD97 expression levels have been detected in 208 out of 385 primary AML samples. This was accompanied by a significantly increased bone marrow blast count as well as by mutations in the FLT3 gene. FLT3-ITD expressing cell lines as MV4-11 and MOLM-13 revealed significantly higher CD97 levels than FLT3 wildtype EOL-1, OCI-AML3 and HL-60 cells which were clearly decreased by the tyrosine kinase inhibitors PKC412 and SU5614. CD97 knock down by short hairpin RNA in MV4-11 cells resulted in inhibited trans-well migration towards fetal calf serum (FCS) and lysophosphatidic acid (LPA) being at least in part Rho-A dependent. Moreover, knock down of CD97 led to an altered mechanical phenotype, reduced adhesion to a stromal layer and lower wildtype FLT3 expression. Our results, thus, constitute the first evidence for the functional relevance of CD97 expression in FLT3-ITD AML cells rendering it a potential new theragnostic target. PMID:26462154

  8. Leukemia and benzene.

    PubMed

    Snyder, Robert

    2012-08-01

    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

  9. Natural Killer Cells Limit Cardiac Inflammation and Fibrosis by Halting Eosinophil Infiltration

    PubMed Central

    Ong, SuFey; Ligons, Davinna L.; Barin, Jobert G.; Wu, Lei; Talor, Monica V.; Diny, Nicola; Fontes, Jillian A.; Gebremariam, Elizabeth; Kass, David A.; Rose, Noel R.; ih獺kov獺, Daniela

    2016-01-01

    Myocarditis is a leading cause of sudden cardiac failure in young adults. Natural killer (NK) cells, a subset of the innate lymphoid cell compartment, are protective in viral myocarditis. Herein, we demonstrated that these protective qualities extend to suppressing autoimmune inflammation. Experimental autoimmune myocarditis (EAM) was initiated in BALB/c mice by immunization with myocarditogenic peptide. During EAM, activated cardiac NK cells secreted interferon 帠, perforin, and granzyme B, and expressed CD69, tumor necrosis factorrelated apoptosis-inducing ligand treatment, and CD27 on their cell surfaces. The depletion of NK cells during EAM with anti-asialo GM1 antibody significantly increased myocarditis severity, and was accompanied by elevated fibrosis and a 10-fold increase in the percentage of cardiac-infiltrating eosinophils. The resultant influx of eosinophils to the heart was directly responsible for the increased disease severity in the absence of NK cells, because treatment with polyclonal antibody asialogangloside GM-1 did not augment myocarditis severity in eosinophil-deficient doubleGATA1 mice. We demonstrate that NK cells limit eosinophilic infiltration both indirectly, through altering eosinophil-related chemokine production by cardiac fibroblasts, anddirectly, by inducing eosinophil apoptosis invitro. Altogether, we define a new pathway of eosinophilic regulation through interactions with NK cells. PMID:25622543

  10. Severe Rhabdomyolysis without Systemic Involvement: A Rare Case of Idiopathic Eosinophilic Polymyositis

    PubMed Central

    Farooq, Ayesha; Choksi, Vivek; Chu, Andrew; Mankodi, Dhruti; Shaharyar, Sameer; O'Brien, Keith; Shankar, Uday

    2015-01-01

    Introduction. Eosinophilic polymyositis (EPM) is a rare cause of rhabdomyolysis characterized by eosinophilic infiltrates in the muscle. We describe the case of a young patient with eosinophilic polymyositis causing isolated severe rhabdomyolysis without systemic involvement. Case Presentation. A 22-year-old Haitian female with no past medical history presented with progressive generalized muscle aches without precipitating factors. Examination of the extremities revealed diffuse muscle tenderness. Laboratory findings demonstrated peripheral eosinophilia and high creatinine phosphokinase (CPK) and transaminase levels. Workup for the common causes of rhabdomyolysis were negative. Her CPK continued to rise to greater than 100,000 units/L so a muscle biopsy was performed which showed widespread eosinophilic infiltrate consistent with eosinophilic polymyositis. She was started on high dose systemic corticosteroids with improvement of her symptoms, eosinophilia, and CPK level. Discussion. This case illustrates a systematic workup of rhabdomyolysis in the presence of peripheral eosinophilia. Many differential diagnoses must be considered before establishing a diagnosis of idiopathic eosinophilic polymyositis. To our knowledge, our case of eosinophilic polymyositis is unique as it presented with severe rhabdomyolysis without another organ involvement. Clinicians should maintain a high index of suspicion for this physically debilitating disease to aid in prompt diagnosis. PMID:26229703

  11. Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions

    PubMed Central

    Kiwamoto, Takumi; Kawasaki, Norihito; Paulson, James C.; Bochner, Bruce S.

    2013-01-01

    Siglecs (sialic acid immunoglobulin-like lectins) are members of the immunoglobulin gene family that contain sialoside binding N-terminal domains. They are cell surface proteins found predominantly on cells of the immune system. Among them, Siglec-8 is uniquely expressed by human eosinophils and mast cells, as well as basophils. Engaging this structure with antibodies or glycan ligands results in apoptosis in human eosinophils and inhibition of release of preformed and newly generated mediators from human mast cells without affecting their survival. Pro-apoptotic effects are also seen when its closest functional paralog, Siglec-F, on mouse eosinophils is similarly engaged in vitro, and beneficial effects are observed after administration of Siglec-F antibody using models of eosinophilic pulmonary and gastrointestinal inflammation in vivo. Siglec-8 targeting may thus provide a means to specifically inhibit or deplete these cell types. Cell-directed therapies are increasingly sought after by the pharmaceutical industry for their potential to reduce side effects and increase safety. The challenge is to identify suitable targets on the cell type of interest, and selectively deliver a therapeutic agent. By targeting Siglec-8, monoclonal antibodies and glycan ligand-conjugated nanoparticles may be ideally suited for treatment of eosinophil and mast cell-related diseases, such as asthma, chronic rhinosinusitis, chronic urticaria, hypereosinophilic syndromes, mast cell and eosinophil malignancies and eosinophilic gastrointestinal disorders. PMID:22749793

  12. Dusp5 negatively regulates IL-33-mediated eosinophil survival and function

    PubMed Central

    Holmes, Derek A; Yeh, Jung-Hua; Yan, Donghong; Xu, Min; Chan, Andrew C

    2015-01-01

    Mitogen-activated protein kinase (MAPK) activation controls diverse cellular functions including cellular survival, proliferation, and apoptosis. Tuning of MAPK activation is counter-regulated by a family of dual-specificity phosphatases (DUSPs). IL-33 is a recently described cytokine that initiates Th2 immune responses through binding to a heterodimeric IL-33R? (ST2L)/IL-1? accessory protein (IL-1RAcP) receptor that coordinates activation of ERK and NF-?B pathways. We demonstrate here that DUSP5 is expressed in eosinophils, is upregulated following IL-33 stimulation and regulates IL-33 signaling. Dusp5?/? mice have prolonged eosinophil survival and enhanced eosinophil effector functions following infection with the helminth Nippostrongylus brasiliensis. IL-33-activated Dusp5?/? eosinophils exhibit increased cellular ERK1/2 activation and BCL-XL expression that results in enhanced eosinophil survival. In addition, Dusp5?/? eosinophils demonstrate enhanced IL-33-mediated activation and effector functions. Together, these data support a role for DUSP5 as a novel negative regulator of IL-33-dependent eosinophil function and survival. PMID:25398911

  13. The effect of ablation of eosinophils on immediate-type hypersensitivity reactions.

    PubMed Central

    Gleich, G J; Olson, G M; Loegering, D A

    1979-01-01

    The effect of ablation of eosinophils on hypersensitivity reactions in guinea-pigs was tested by administration of rabbit antiserum to the eosinophil (AES) and by administration of glucocorticoids. Both AES and methylprednisolone ablated eosinophils from the blood and peritoneal cavity of test animals. Neither administration of AES nor methylprednisolone, however, altered passive cutaneous or systemic anaphylactic reactions when compared to reactions occurring in control animals treated with normal rabbit serum (NRS). Also there was no consistent effect of AES on the intensity of the Arthus reaction. The effect of ablation of eosinophils on histamine release in the passively sensitized peritoneal cavity of the guinea-pig was also tested. In five experiments a significant reduction in histamine release was seen in AES-treated animals. Ablation of eosinophils by cortisone acetate also resulted in a marked reduction in the quantity of histamine released into the peritoneal cavity following passive sensitization and antigen challenge. Histamine release following intraperitoneal injection of compound 48/80 was not affected by either the prior administration of AES or cortisone acetate, suggesting that the stores of histamine were not depleted by these agents. Overall these results suggest that eosinophils do not play a prominent role in initial expression of immediate-type hypersensitivity reactions where the density of these cells in tissues is low. When present in larger numbers, however, eosinophils may contribute to histamine release in immediate-type reactions. PMID:92457

  14. Pathogenesis and classification of eosinophil disorders: a review of recent developments in the field.

    PubMed

    Valent, Peter; Gleich, Gerald J; Reiter, Andreas; Roufosse, Florence; Weller, Peter F; Hellmann, Andrzej; Metzgeroth, Georgia; Leiferman, Kristin M; Arock, Michel; Sotlar, Karl; Butterfield, Joseph H; Cerny-Reiterer, Sabine; Mayerhofer, Matthias; Vandenberghe, Peter; Haferlach, Torsten; Bochner, Bruce S; Gotlib, Jason; Horny, Hans-Peter; Simon, Hans-Uwe; Klion, Amy D

    2012-04-01

    Eosinophils and their products play an essential role in the pathogenesis of various reactive and neoplastic disorders. Depending on the underlying disease, molecular defect and involved cytokines, hypereosinophilia may develop and may lead to organ damage. In other patients, persistent eosinophilia is accompanied by typical clinical findings, but the causative role and impact of eosinophilia remain uncertain. For patients with eosinophil-mediated organ pathology, early therapeutic intervention with agents reducing eosinophil counts can be effective in limiting or preventing irreversible organ damage. Therefore, it is important to approach eosinophil disorders and related syndromes early by using established criteria, to perform all appropriate staging investigations, and to search for molecular targets of therapy. In this article, we review current concepts in the pathogenesis and evolution of eosinophilia and eosinophil-related organ damage in neoplastic and non-neoplastic conditions. In addition, we discuss classifications of eosinophil disorders and related syndromes as well as diagnostic algorithms and standard treatment for various eosinophil-related disorders. PMID:22475285

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

    MedlinePLUS

    ... With Bullies Pregnant? What to Expect Juvenile Myelomonocytic Leukemia (JMML) KidsHealth > Parents > Diseases & Conditions > Cancer & Tumors > Juvenile ... Causes Signs and Symptoms Diagnosis Treatment Coping About Leukemia Leukemia is a type of cancer that affects ...

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

    MedlinePLUS

    ... With Bullies Pregnant? What to Expect Chronic Myelogenous Leukemia (CML) KidsHealth > Parents > Diseases & Conditions > Cancer & Tumors > Chronic ... Causes Signs and Symptoms Diagnosis Treatment Coping About Leukemia Leukemia is a type of cancer that affects ...

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

    MedlinePLUS

    ... With Bullies Pregnant? What to Expect Acute Myeloid Leukemia (AML) KidsHealth > Parents > Diseases & Conditions > Cancer & Tumors > Acute ... Causes Signs and Symptoms Diagnosis Treatment Coping About Leukemia Leukemia is a type of cancer that affects ...

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

    ClinicalTrials.gov

    2015-07-27

    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

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

    ClinicalTrials.gov

    2016-03-11

    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

  20. Fasciola hepatica induces eosinophil apoptosis in the migratory and biliary stages of infection in sheep.

    PubMed

    Escamilla, A; Bautista, M J; Zafra, R; Pacheco, I L; Ruiz, M T; Mart璯ez-Cruz, S; M幯dez, A; Mart璯ez-Moreno, A; Molina-Hern嫕dez, V; P廨ez, J

    2016-01-30

    The aim of the present work was to evaluate the number of apoptotic eosinophils in the livers of sheep experimentally infected with Fasciola hepatica during the migratory and biliary stages of infection. Four groups (n=5) of sheep were used; groups 1-3 were orally infected with 200 metacercariae (mc) and sacrificed at 8 and 28 days post-infection (dpi), and 17 weeks post-infection (wpi), respectively. Group 4 was used as an uninfected control. Apoptosis was detected using immunohistochemistry with a polyclonal antibody against anti-active caspase-3, and transmission electron microscopy (TEM). Eosinophils were identified using the Hansel stain in serial sections for caspase-3, and by ultrastructural features using TEM. At 8 and 28 dpi, numerous caspase-3(+) eosinophils were mainly found at the periphery of acute hepatic necrotic foci. The percentage of caspase -3(+) apoptotic eosinophils in the periphery of necrotic foci was high (46.1-53.9) at 8 and 28 dpi, respectively, and decreased in granulomas found at 28 dpi (6%). Transmission electron microscopy confirmed the presence of apoptotic eosinophils in hepatic lesions at 8 and 28 dpi. At 17 wpi, apoptotic eosinophils were detected in the infiltrate surrounding some enlarged bile ducts containing adult flukes. This is the first report of apoptosis induced by F. hepatica in sheep and the first study reporting apoptosis in eosinophils in hepatic inflammatory infiltrates in vivo. The high number of apoptotic eosinophils in acute necrotic tracts during the migratory and biliary stages of infection suggests that eosinophil apoptosis may play a role in F. hepatica survival during different stages of infection. PMID:26801599

  1. A parallel signal-transduction pathway for eotaxin- and interleukin-5-induced eosinophil shape change

    PubMed Central

    Choi, Eun Nam; Choi, Moon Kyung; Park, Choon-Sik; Chung, Il Yup

    2003-01-01

    Interleukin-5 (IL-5) and eotaxin are the most important cytokines/chemokines responsible for regulating eosinophil locomotion and are known to play a co-operative role in the selective recruitment of eosinophils to inflamed tissues. Following exposure to chemoattractants, eosinophils undergo a series of events, including reorganization of actin filaments and subsequent rapid shape changes, culminating in chemotaxis. In this study we examined the signalling pathways for eosinophil shape change regulated by eotaxin and IL-5, primarily using a gated autofluorescence/forward-scatter assay. Eotaxin and IL-5 were able to elicit shape change with peaks at 10 and 60 min, respectively, and IL-5 triggered the shape change more efficiently than eotaxin. The pharmacological inhibitors of mitogen-activated protein kinase (MAP kinase) and p38 blocked both eotaxin- and IL-5-induced eosinophil shape change in a dose-dependent manner. In addition, depletion of intracellular Ca2+ and inhibition of protein kinase A (PKA) strongly reduced eosinophil shape change. In contrast, even when used at high concentrations, protein tyrosine kinase (PTK) inhibitors caused only a slight reduction in the ability to change shape. However, treatment with protein kinase C (PKC) inhibitors, such as GF109203X and staurosporine, resulted in a striking inhibition of eosinophil shape change by IL-5, but not eotaxin. Data from the inhibition of activation and chemotaxis of the extracellular signal-regulated kinases (ERK1/2) by the PKC inhibitors were also consistent with findings from the experiments on shape change. Collectively, two eosinophil-selective cytokines/chemokines probably regulate eosinophil shape change via a largely overlapping signalling pathway, with involvement of PKC restricted to the IL-5 signal alone. PMID:12562334

  2. Eosinophil resistance to glucocorticoid-induced apoptosis is mediated by the transcription factor NFIL3.

    PubMed

    Pazdrak, Konrad; Moon, Young; Straub, Christof; Stafford, Susan; Kurosky, Alexander

    2016-04-01

    The mainstay of asthma therapy, glucocorticoids (GCs) exert their therapeutic effects through the inhibition of inflammatory signaling and induction of eosinophil apoptosis. However, laboratory and clinical observations of GC-resistant asthma suggest that GCs' effects on eosinophil viability may depend on the state of eosinophil activation. In the present study we demonstrate that eosinophils stimulated with IL-5 show impaired pro-apoptotic response to GCs. We sought to determine the contribution of GC-mediated transactivating (TA) and transrepressing (TR) pathways in modulation of activated eosinophils' response to GC by comparing their response to the selective GC receptor (GR) agonist Compound A (CpdA) devoid of TA activity to that upon treatment with Dexamethasone (Dex). IL-5-activated eosinophils showed contrasting responses to CpdA and Dex, as IL-5-treated eosinophils showed no increase in apoptosis compared to cells treated with Dex alone, while CpdA elicited an apoptotic response regardless of IL-5 stimulation. Proteomic analysis revealed that both Nuclear Factor IL-3 (NFIL3) and Map Kinase Phosphatase 1 (MKP1) were inducible by IL-5 and enhanced by Dex; however, CpdA had no effect on NFIL3 and MKP1 expression. We found that inhibiting NFIL3 with specific siRNA or by blocking the IL-5-inducible Pim-1 kinase abrogated the protective effect of IL-5 on Dex-induced apoptosis, indicating crosstalk between IL-5 anti-apoptotic pathways and GR-mediated TA signaling occurring via the NFIL3 molecule. Collectively, these results indicate that (1) GCs' TA pathway may support eosinophil viability in IL-5-stimulated cells through synergistic upregulation of NFIL3; and (2) functional inhibition of IL-5 signaling (anti-Pim1) or the use of selective GR agonists that don't upregulate NFIL3 may be effective strategies for the restoring pro-apoptotic effect of GCs on IL-5-activated eosinophils. PMID:26880402

  3. Activated eosinophils in adult coeliac disease: evidence for a local release of major basic protein.

    PubMed Central

    Colombel, J F; Torpier, G; Janin, A; Klein, O; Cortot, A; Capron, M

    1992-01-01

    The eosinophil population is increased in the jejunal mucosa of patients with coeliac disease. Eosinophils may participate in the mucosal damage by releasing their granule components that have cytotoxic properties such as eosinophil cationic protein (ECP) and major basic protein (MBP). This study aimed to assess the presence of ECP and MBP in the jejunal mucosa of 10 adult patients with active coeliac disease who presented with villous flattening. Endoscopic jejunal biopsy specimens were obtained from macroscopically flattened jejunal mucosa and were processed for ultrastructural study and immunogold labelling using anti-MBP, anti-ECP, and anti-IgA antibodies. Numerous eosinophils were found in the upper part of the lamina propria and showed two types of morphological change: some were lytic and others exhibited ultrastructural signs of activation, containing altered granules with fading of the central core. IgA plasma cells were intermingled with eosinophils and had dense deposits on the external side of their cytoplasmic membrane. MBP was detected in central cores of granules but also diffusely in their matrix and in tight association with dense extracellular deposits. Conversely, ECP was detected only in the matrix of eosinophil granules. This study showed that numerous eosinophils are in an activated state in the mucosa of patients with active coeliac disease and release cytotoxic proteins such as MBP, which could contribute to the mucosal damage. The observation that eosinophils and IgA plasmocytes were closely associated in the mucosa supports a role for IgA in eosinophil recruitment and activation in coeliac disease. Images Figure 1 Figure 2 PMID:1427370

  4. Volatile organic compounds discriminate between eosinophilic and neutrophilic inflammation in vitro.

    PubMed

    Schleich, Florence N; Dallinga, Jan W; Henket, Monique; Wouters, Emiel F M; Louis, Renaud; Van Schooten, Frederik J

    2016-01-01

    Inflammation associated oxidative stress leads to peroxidation of polyunsaturated fatty acids thereby generating volatile organic compounds (VOCs). The integrative analysis of the total amount of VOCs released by eosinophils and neutrophils in vitro enables the search for those compounds that discriminates between various inflammatory conditions. The approach comprises isolating eosinophils and neutrophils from 30ml of blood of healthy non-smoking volunteers by gradient centrifugation, using lymphoprep. Eosinophils are separated from neutrophils by immunomagnetic cell separation using anti-CD16. Cells are activated with phorbol 12-myristate 13-acetate and VOCs from the headspace are collected at time 0', 30', 60' and 90' by introduction of ultra-pure nitrogen in the closed flasks at a flow rate of 200ml min(-1) during 10min. The gases are trapped onto a sorption tube and analyzed by gas chromatography-time-of-flight-mass spectometry (GC-TOF-MS) in order to identify VOCs released in the headspace by activated neutrophils and eosinophils. Eosinophils and neutrophils were isolated from 26 healthy non-smoking volunteers. The average absolute number of eosinophils and neutrophils upon isolation was 3.510(6) and 19.410(6), respectively. The volatome in headspace consisted of 2116 compounds and those compounds present in at least 8% of the samples (1123 compounds) were used for further discriminant analysis. Discriminant analysis showed that two VOCs were able to distinguish between eosinophilic and neutrophilic cultures in the unactivated state with 100% correct classification of the entire data set and upon cross validation while five VOCs were able to discriminate between activated eosinophils and neutrophils with 96% correct classification in the original set and upon cross-validation. Analysis of VOCs seems to be a very promising approach in identifying eosinophilic and neutrophilic inflammation but it needs further development and in vivo confirmation. PMID:26828318

  5. Blood eosinophils and inhaled corticosteroid/long-acting 帣-2 agonist efficacy in COPD

    PubMed Central

    Pavord, Ian D; Lettis, Sally; Locantore, Nicholas; Pascoe, Steve; Jones, Paul W; Wedzicha, Jadwiga A; Barnes, Neil C

    2016-01-01

    Objective We performed a review of studies of fluticasone propionate (FP)/salmeterol (SAL) (combination inhaled corticosteroid (ICS)/long-acting 帣2-agonist (LABA)) in patients with COPD, which measured baseline (pretreatment) blood eosinophil levels, to test whether blood eosinophil levels 2% were associated with a greater reduction in exacerbation rates with ICS therapy. Methods Three studies of 1-year duration met the inclusion criteria. Moderate and severe exacerbation rates were analysed according to baseline blood eosinophil levels (<2% vs 2%). At baseline, 5775% of patients had 2% blood eosinophils. Changes in FEV1 and St George's Respiratory Questionnaire (SGRQ) scores were compared by eosinophil level. Results For patients with 2% eosinophils, FP/SAL was associated with significant reductions in exacerbation rates versus tiotropium (INSPIRE: n=719, rate ratio (RR)=0.75, 95% CI 0.60 to 0.92, p=0.006) and versus placebo (TRISTAN: n=1049, RR=0.63, 95% CI 0.50 to 0.79, p<0.001). No significant difference was seen in the <2% eosinophil subgroup in either study (INSPIRE: n=550, RR=1.18, 95% CI 0.92 to 1.51, p=0.186; TRISTAN: n=354, RR=0.99, 95% CI 0.67 to 1.47, p=0.957, respectively). In SCO30002 (n=373), no significant effects were observed (FP or FP/SAL vs placebo). No relationship was observed in any study between eosinophil subgroup and treatment effect on FEV1 and SGRQ. Discussion Baseline blood eosinophil levels may represent an informative marker for exacerbation reduction with ICS/LABA in patients with COPD and a history of moderate/severe exacerbations. PMID:26585525

  6. Eosinophils and mast cells in chronic gastritis: Possible implications in carcinogenesis

    PubMed Central

    Piazuelo, M. Blanca; Camargo, M. Constanza; Mera, Robertino M.; Delgado, Alberto G.; Peek, Richard M.; Correa, Hernan; Schneider, Barbara G.; Sicinschi, Liviu A.; Mora, Yolanda; Bravo, Luis E.; Correa, Pelayo

    2008-01-01

    Eosinophils and mast cells participate in the immune response against Helicobacter pylori, but their involvement in the gastric precancerous process is unclear. This study aimed to estimate eosinophil and mast cell density in antral mucosa in subjects from two Colombian populations with contrasting gastric cancer risks. Gastric mucosa biopsies were collected from 117 adult males (72 from a high-risk area and 45 from a low-risk area). A histopathology score was used to quantify severity of the lesions. Quantitation of eosinophils in hematoxylin-eosin stained sections and mast cells in immunostained sections for CD117/c-Kit was performed. Helicobacter pylori infection and genotyping were assessed in Steiner stain and PCR, respectively. Logistic regression models and semi-parametric cubic smoothing splines were used for analysis of the results. Eosinophil density was significantly higher in subjects from the low-risk area compared with subjects from the high-risk area. In both populations, eosinophil density increased with the histopathology score in the progression of lesions from normal morphology to multifocal atrophic gastritis. Intestinal metaplasia and dysplasia specimens showed further increase in eosinophil density in the high-risk area, but an abrupt decrease in the low-risk area. Mast cell density increased in parallel to the histopathology score in both populations. Our results suggest that eosinophils play a dual role in chronic gastritis. In the low-risk area, elevated eosinophil density represents a Th2-biased response that may downregulate the effects of proinflammatory cytokines preventing cancer development. In contrast, in the high-risk area, eosinophils might promote a Th1-type response leading to progression of precancerous lesions. PMID:18614201

  7. Eosinophil-activating factor (EAF) production by a human cell line (ESH 98) stimulated with tumour necrosis factor.

    PubMed Central

    Thorne, K J; Richardson, B A; Butterworth, A E; Stanley, M

    1988-01-01

    A new cell line has been produced by fusing human cervical keratinocytes with HeLa cells. This cell line secretes eosinophil-activating activity upon stimulation with tumour necrosis factor (TNF). About one-third of the eosinophil-activating activity co-purifies with eosinophil-activating factor (EAF) from mononuclear cell supernatants. The purification procedure indicates that it resembles EAF in molecular weight and acidity. It also resembles EAF in its effect on eosinophils. Not only does it enhance the cytotoxic activity of eosinophils to antibody-coated schistosomula of Schistosoma mansoni, but it also increases the oxidative activity of eosinophils, as measured by reduction of nitroblue tetrazolium, and changes the morphology of eosinophils, affecting the distribution of F-actin in the cell. Images Figure 3 PMID:2450839

  8. Mechanisms of eosinophil secretion: large vesiculotubular carriers mediate transport and release of granule-derived cytokines and other proteins.

    PubMed

    Melo, Rossana C N; Spencer, Lisa A; Dvorak, Ann M; Weller, Peter F

    2008-02-01

    Eosinophils generate and store a battery of proteins, including classical cationic proteins, cytokines, chemokines, and growth factors. Rapid secretion of these active mediators by eosinophils is central to a range of inflammatory and immunoregulatory responses. Eosinophil products are packaged within a dominant population of cytoplasmic specific granules and generally secreted by piecemeal degranulation, a process mediated by transport vesicles. Large, pleiomorphic vesiculotubular carriers were identified recently as key players for moving eosinophil proteins from granules to the plasma membrane for extracellular release. During secretion, these specialized, morphologically distinct carriers, termed eosinophil sombrero vesicles, are actively formed and direct differential and rapid release of eosinophil proteins. This review highlights recent discoveries concerning the organization of the human eosinophil secretory pathway. These discoveries are defining a broader role for large vesiculotubular carriers in the intracellular trafficking and secretion of proteins, including selective receptor-mediated mobilization and transport of cytokines. PMID:17875811

  9. Eosinophilic Gastroenteritis Due to Rhus Ingestion Presenting with Gastrointestinal Hemorrhage

    PubMed Central

    Choi, Wonsuk; Choi, Chan; Cho, Kyuman; Park, Chang-Hwan; Kim, Hyun-Soo; Choi, Sung-Kyu; Rew, Jong-Sun

    2015-01-01

    Rhus-related illnesses in Korea are mostly caused by ingestion of parts of the Rhus tree. Contact dermatitis occurrence after ingestion of Rhus-related food is very common in Korea. However, Rhus-related gastrointestinal disease is very rare. Herein, we present a case of eosinophilic gastroenteritis caused by Rhus ingestion. A 75-year-old woman was admitted with hematemesis and hematochezia after Rhus extract ingestion. Routine laboratory tests revealed leukocytosis without eosinophilia. Endoscopy showed friable and granular mucosal changes with touch bleeding in the second portion of the duodenum. Abdominal computed tomography revealed edematous wall thickening of the duodenum and proximal jejunal loops. Patch testing with Rhus extracts showed a strong positive reaction, suggesting Rhus as the allergen. Her symptoms improved after avoidance of the allergen. PMID:25844348

  10. Mucosal immunology, eosinophilic esophagitis, and other intestinal inflammatory diseases.

    PubMed

    Atkins, Dan; Furuta, Glenn T

    2010-02-01

    The gastrointestinal mucosa constitutes the largest host-environment interface of the body. It uses both innate and adaptive immune mechanisms to provide protection from the diverse onslaught of foods, microbes, and other ingested products. The innate immune system is genetically encoded and evolutionarily ancient, possesses no memory, and lacks diversity. In contrast, the adaptive immune system is quite diverse, develops memory, and undergoes expansion after stimulation. The gastrointestinal mucosa is charged with the difficult task of mounting protective responses against invading microorganisms while simultaneously maintaining an overall state of nonresponsiveness or tolerance to innocuous substances, such as commensal bacteria and food antigens. Perturbation or malfunction of these complex protective mechanisms results in diseases, such as inflammatory bowel diseases, celiac disease, or eosinophilic gastrointestinal diseases. PMID:20176262

  11. Eosinophilic and granular cell tumors of the breast.

    PubMed

    Damiani, S; Dina, R; Eusebi, V

    1999-05-01

    Eosinophilic and granular cell tumors of the breast are a heterogeneous group encompassing both epithelial and mesenchymal lesions. A granular appearance of the cytoplasm may be caused by the accumulation of secretory granules, mitochondria, or lysosomes. In the breast, mucoid carcinomas, carcinomas showing apocrine differentiation, and neuroendocrine carcinomas are well known entities, while tumors with oncocytic and acinic cell differentiation have been only recently recognized. An abundance of lysosomes is characteristic of Schwannian granular cell neoplasms, but smooth muscle cell tumors also may have this cytoplasmic feature. Awareness of all these possibilities when granular cells are found in breast lesions improves diagnostic accuracy and helps to avoid misdiagnosis of both benign lesions and malignant tumors. PMID:10452577

  12. Dividing the Janus vasculitis? Pathophysiology of eosinophilic granulomatosis with polyangitis.

    PubMed

    Chaigne, Benjamin; Terrier, Benjamin; Thieblemont, Nathalie; Witko-Sarsat, V廨onique; Mouthon, Luc

    2016-02-01

    Eosinophilic granulomatosis with polyangitis (EGPA) is a rare small- and medium-sized vessel vasculitis belonging to the group of anti-neutrophil cytoplasm antibody (ANCA)-associated vasculitides (AAV). It is commonly divided into two phenotypes depending on the presence of ANCAs targeting myeloperoxidase (MPO). MPO-ANCAs are present in 31% to 38% of patients and are associated with a vasculitis phenotype of the disease, whereas patients without MPO-ANCA are at risk of cardiac involvement. Despite significant advances in understanding the overall pathogenesis of the disease, the explanation for this dichotomy is still unclear. In this review, we synthesize our knowledge of the pathogenesis of EGPA and attempt to i) distinguish EGPA from other diseases including other AAVs, asthma, allergy and hypereosinophilic-associated conditions and ii) speculate about the preponderant mechanisms, which could explain the two disease phenotypes. PMID:26506114

  13. Translating New Developments in Eosinophilic Esophagitis Pathogenesis into Clinical Practice

    PubMed Central

    Cheng, Edaire

    2015-01-01

    Opinion Statement New developments in eosinophilic esophagitis pathogenesis are shaping our current therapeutic and management strategies. EoE is a chronic allergic inflammatory disease with progression to fibrostenotic disease. The disease warrants early diagnosis and long-term maintenance therapy. The diagnosis of EoE should be based on the concept of an allergy-mediated disease with esophageal dysfunction and esophageal eosinophilia. Recent findings suggest PPI-REE is likely a continuum of EoE or similar Th2-mediated allergic process. PPIs have therapeutic properties that can benefit both GERD and EoE. Therefore, PPIs should not be considered a diagnostic tool, but rather a therapeutic option for EoE. If patients are PPI-nonresponsive, then dietary therapy or steroid therapy should be considered. Dilation can be reserved as adjuvant therapy for severe fibrostenotic lesions. PMID:25598233

  14. Characterization of eosinophilic esophagitis murine models using optical coherence tomography

    PubMed Central

    Alex, Aneesh; Noti, Mario; Wojno, Elia D. Tait; Artis, David; Zhou, Chao

    2014-01-01

    Pre-clinical studies using murine models are critical for understanding the pathophysiological mechanisms underlying immune-mediated disorders such as Eosinophilic esophagitis (EoE). In this study, an optical coherence tomography (OCT) system capable of providing three-dimensional images with axial and transverse resolutions of 5 痠 and 10 痠, respectively, was utilized to obtain esophageal images from a murine model of EoE-like disease ex vivo. Structural changes in the esophagus of wild-type (Tslpr+/+) and mutant (Tslpr?/?) mice with EoE-like disease were quantitatively evaluated and food impaction sites in the esophagus of diseased mice were monitored using OCT. Here, the capability of OCT as a label-free imaging tool devoid of tissue-processing artifacts to effectively characterize murine EoE-like disease models has been demonstrated. PMID:24575353

  15. An allergist's perspective to the evaluation of Eosinophilic Esophagitis.

    PubMed

    Spergel, Jonathan M

    2015-10-01

    Eosinophilic Esophagitis (EoE) is a classic atopic disease as it shares features with other atopic disease on all levels including pathogenesis, genetics, epidemiology, and treatment options. EoE has elements of Th2 pathogenesis with increase levels of Th2 cytokines (IL4, 5, and 13). In addition, it shares atopic genetic risk factors including thymic stromal lymphopoietin (TSLP) loci as a risk factor in genome wide association studies. EoE patients have a higher rate of other atopic disease (asthma, allergic rhinitis and food allergy) compared to the general population indicating their atopic phenotype. Like asthma, atopic dermatitis or food allergy, EoE has increased in the last 20 years. Treatment options include the basic principle of other atopic diseases include using topical steroids or avoidance of the triggers (food or pollen). An allergist provides a critical role as they are experts in the treatment of atopic disease including avoidance strategies. PMID:26552776

  16. Eosinophilic Esophagitis: Another Atopy-Related Alopecia Areata Trigger?

    PubMed

    Ibrahim, Omer; Bergfeld, Wilma F; Piliang, Melissa

    2015-11-01

    Alopecia areata (AA) is associated with atopy in 10-22% of patients, twice the prevalence in the general population. Patients can present with concomitant atopic dermatitis, hay fever, asthma, and even allergies to dust mites. In many cases, severity and flares of these atopic diatheses correlate with severity of AA. Herein we present a patient with AA affected by contemporaneous eosinophilic esophagitis (EoE). EoE is a recently recognized allergic disorder, mediated by eosiniphils and histamine. It is characterized by esophageal dysfunction and intraepithelial microabscesses. We propose that EoE be considered as a condition falling within the realm of atopic diseases, and a potential trigger of AA in affected patients. PMID:26551950

  17. 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

  18. Esophageal human beta-defensin expression in eosinophilic esophagitis

    PubMed Central

    Schroeder, Shauna; Robinson, Zachary D.; Masterson, Joanne C.; Hosford, Lindsay; Moore, Wendy; Pan, Zhaoxing; Harris, Rachel; Souza, Rhonda F.; Spechler, Stuart Jon; Fillon, Sophie A.; Furuta, Glenn T.

    2013-01-01

    Background Defensins are antimicrobial peptides expressed on mucosal surfaces that contribute to maintaining intestinal homeostasis by providing innate defense mechanisms for the epithelia. Defensin expression is altered in a number of diseases that affect mucosal surfaces, such as atopic dermatitis, allergic rhinitis, and inflammatory bowel disease. Similar to atopic dermatitis, eosinophilic esophagitis (EoE) is a chronic disease in which the squamous epithelial surface is affected by a similar TH2 microenvironment and eosinophil predominant inflammation. Therefore, we hypothesized defensin expression would be decreased in EoE. Methods To address this, we measured defensin expression in vitro in cell lines derived from patients with EoE (EoE1-T) or gastroesophageal reflux disease (GERD) (NES-G4T cells), and ex vivo in esophageal mucosal biopsy samples from children with EoE, GERD, and control children without esophageal disease. Results IL-5 induced a decrease in human beta-defensin 1 (hBD1) and human beta-defensin 3 (hBD3) expression in EoE1-T but not in NES-G4T cells. Compared to esophageal biopsy specimens from GERD and control children, specimens from EoE pediatric patients revealed significant decrease in mRNA and protein expression for hBD1 and hBD3. Conclusion Diminished expression of hBD1 and hBD3 may make the esophageal epithelium more susceptible to the development and/or perpetuation of EoE. PMID:23385963

  19. Eosinophilic esophagitis in patients with esophageal atresia and chronic dysphagia

    PubMed Central

    Kassabian, Sirvart; Baez-Socorro, Virginia; Sferra, Thomas; Garcia, Reinaldo

    2014-01-01

    Esophageal atresia (EA) is defined as a discontinuity of the lumen of the esophagus repaired soon after birth. Dysphagia is a common symptom in these patients, usually related to stricture, dysmotility or peptic esophagitis. We present 4 cases of patients with EA who complained of dysphagia and the diagnosis of Eosinophilic esophagitis (EoE) was made, ages ranging from 9 to 16 years. Although our patients were on acid suppression years after their EA repair, they presented with acute worsening of dysphagia. Esophogastroduodenoscopy and/or barium swallow did not show stricture and biopsies revealed elevated eosinophil counts consistent with EoE. Two of 4 patients improved symptomatically with the topical steroids. It is important to note that all our patients have asthma and 3 out of 4 have tested positive for food allergies. One of our patients developed recurrent anastomotic strictures that improved with the treatment of the EoE. A previous case report linked the recurrence of esophageal strictures in patients with EA repair with EoE. Once the EoE was treated the strictures resolved. On the other hand, based on our observation, EoE could be present in patients without recurrent anastomotic strictures. There appears to be a spectrum in the disease process. We are suggesting that EoE is a frequent concomitant problem in patients with history of congenital esophageal deformities, and for this reason any of these patients with refractory reflux symptoms or dysphagia (with or without anastomotic stricture) may benefit from an endoscopic evaluation with biopsies to rule out EoE. PMID:25548504

  20. Ultrastructural features of eosinophilic oesophagitis: impact of treatment on desmosomes

    PubMed Central

    Capocelli, Kelley E; Fernando, Shahan D; Menard-Katcher, Calies; Furuta, Glenn T; Masterson, Joanne C; Wartchow, Eric P

    2015-01-01

    Aims A growing body of evidence suggests a role for altered epithelial barrier function in the pathophysiology of eosinophilic oesophagitis (EoE), but few have described the epithelial structure during inflammation. The purpose of this study was to define ultrastructural features of active, inactive EoE and control subjects oesophageal epithelia. Methods We prospectively enrolled patients undergoing diagnostic upper endoscopy for evaluation of EoE. Mucosal pinch biopsies were obtained from the distal oesophagus and processed for routine histology and electron microscopic assessment. Clinical features of enrolled subjects were analysed and subjects were divided into four groups: normal, gastroesophageal reflux disease (GERD), inactive EoE and active EoE. Representative photomicrographs of the basal and superficial epithelia were reviewed for abnormalities. Desmosomes were quantified on the surface of epithelia three to four prickle-cell layers above the basal layer. Results Twenty-nine paediatric cases (ages 218 years) were enrolled in the study. We observed a significant decrease in the number of desmosomes per cell (DPC) of subjects with active EoE compared with inactive EoE, GERD and normal epithelia. With respect to DPC, no significant differences were found between inactive EoE compared with GERD or normal subjects. Additional ultrastructural features observed included epithelial microplicae and evidence of eosinophil transmigration, degranulation, and sombrero formation. Conclusions Consistent with clinical and molecular findings, our ultrastructural data provide support for an altered oesophageal barrier in paediatric cases with active EoE, which may improve following treatment. PMID:25359789

  1. [Infant acute leukemia].

    PubMed

    Brethon, Beno簾t; Cav矇, H矇l癡ne; Fahd, Mony; Baruchel, Andr矇

    2016-03-01

    If acute leukemia is the most frequent cancer in childhood (33%), it remains a very rare diagnosis in infants less than one year old, e.g. less than 5% of cases. At this age, the frequency of acute lymphoblastic leukemia (ALL) (almost all of B-lineage) is quite similar to the one of myeloblastic forms (AML). Infant leukemia frequently presents with high hyperleucocytosis, major tumoral burden and numerous extra-hematological features, especially in central nervous system and skin. Whatever the lineage, the leukemic cell is often very immature cytologically and immunologically. Rearrangements of the Mixed Lineage Leukemia (MLL) gene, located on band11q23, are the hallmark of these immature leukemias and confer a particular resistance to conventional approaches, corticosteroids and chemotherapy. The immaturity of infants less than 1-year-old is associated to a decrease of the tolerable dose-intensity of some drugs (anthracyclines, alkylating agents) or asks questions about some procedures like radiotherapy or high dose conditioning regimen, responsible of inacceptable acute and late toxicities. The high level of severe infectious diseases and other high-grade side effects limits also the capacity to cure these infants. The survival of infants less than 1-year-old with AML is only 50% but similar to older children. On the other hand, survival of those with ALL is the same, then quite limited comparing the 80% survival in children over one year. Allogeneic stem cell transplantations are indicated in high-risk subgroups of infant ALL (age below 6months, high hyperleucocytosis >300.10(9)/L, MLL-rearrangement, initial poor prednisone response). However, morbidity and mortality remain very important and these approaches cannot be extended to all cases. During the neonatal period, the dismal prognosis linked to the high number of primary failures or very early relapses and uncertainties about the late toxicities question physicians about ethics. It is an emergency to propose different strategies (targeted therapies) to these infants with acute leukemia as conventional trials failed to improve outcome. PMID:26826739

  2. 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

  3. 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

  4. Interrelationship of chronic eosinophilic pneumonia, bronchiolitis obliterans, and rheumatoid disease: a hypothesis.

    PubMed Central

    Cooney, T P

    1981-01-01

    Three patients with histologically proven bronchiolitis obliterans are presented, two of whom had rheumatoid disease. All three patients had, in addition, clinical and radiological evidence of chronic eosinophilic pneumonia; open lung biopsy in two showed coexistent features of chronic eosinophilic pneumonia and bronchiolitis obliterans. The association of both rheumatoid disease are chronic eosinophilic pneumonia with bronchiolitis obliterans in these patients may simply be coincidental, but the striking similarities between the cases suggest that a real interrelationship of these disease entities may exist. Images 1b-1e 1a Fig. 2 Fig. 3 Fig. 4 PMID:7229091

  5. A Rare Case of Ibuprofen-Induced Eosinophilic Meningitis in a 13-Year-Old Girl

    PubMed Central

    Bansal, Sharad; Gupta, Mukesh; Sharma, Deepak; Bansal, Shweta

    2014-01-01

    Eosinophilic meningoencephalitis is based on clinical manifestations and microscopic identification of eosinophils present in cerebrospinal fluid (CSF). It is caused by a variety of helminthic infections with most common being angiostrongyliasis, gnathostomiasis, toxocariasis, cysticercosis, schistosomiasis, baylisascariasis, and paragonimiasis. Many case reports are there in which parasites have been found responsible, but there are rare reports of CSF eosinophilia associated with the use of drugs. We report a case of drug-induced (ibuprofen) eosinophilic meningitis in a healthy female who presented to us with severe headache and improved dramatically after drug withdrawal. PMID:24596473

  6. Eosinophilic gastroenteritis complicated with Helicobacter pylori infection unresponsive to eradication therapy.

    PubMed

    Nakamura, Akira; Iwaya, Yugo; Iwaya, Mai; Okamura, Takuma; Kobayashi, Satoshi; Daikuhara, Seiichi; Nozawa, Yuichi; Fukuzawa, Shinya; Nakamura, Shinichiro; Okuhara, Sadahisa; Yamada, Shigenori; Yokosawa, Shuichi; Suga, Tomoaki; Arakura, Norikazu; Tanaka, Eiji

    2014-01-01

    An adolescent girl presented with inappetence. Upper gastrointestinal endoscopy showed rough and cracked mucosa at the gastric antrum with a scarred duodenal ulcer, and a biopsy sample demonstrated abundant eosinophils. We therefore diagnosed the patient as having eosinophilic gastroenteritis. Eradication therapy for Helicobacter pylori (H. pylori) did not improve her symptoms; however, proton pump inhibitor therapy was effective in resolving her chief complaints. There are several reports of eosinophilic gastroenteritis complicated with H. pylori infection in which the association between eradication therapy and the patient's symptoms is unclear. In the present case, the patient's symptoms did not improve with eradication therapy, and there appeared to be no relationship between the two. PMID:25224188

  7. CCR2 deficiency leads to increased eosinophils, alternative macrophage activation, and type 2 cytokine expression in adipose tissue.

    PubMed

    Bolus, W Reid; Gutierrez, Dario A; Kennedy, Arion J; Anderson-Baucum, Emily K; Hasty, Alyssa H

    2015-10-01

    Adipose tissue (AT) inflammation during obesity is mediated by immune cells and closely correlates with systemic insulin resistance. In lean AT, eosinophils are present in low but significant numbers and capable of promoting alternative macrophage activation in an IL-4/IL-13-dependent manner. In WT mice, obesity causes the proportion of AT eosinophils to decline, concomitant with inflammation and classical activation of AT macrophages. In this study, we show that CCR2 deficiency leads to increased eosinophil accumulation in AT. Furthermore, in contrast to WT mice, the increase in eosinophils in CCR2(-/-) AT is sustained and even amplified during obesity. Interestingly, a significant portion of eosinophils is found in CLSs in AT of obese CCR2(-/-) mice, which is the first time eosinophils have been shown to localize to these inflammatory hot spots. CCR2(-/-) bone marrow precursors displayed increased expression of various key eosinophil genes during in vitro differentiation to eosinophils, suggesting a potentially altered eosinophil phenotype in the absence of CCR2. In addition, the proportion of eosinophils in AT positively correlated with local expression of Il5, a potent eosinophil stimulator. The increase in eosinophils in CCR2(-/-) mice was detected in all white fat pads analyzed and in the peritoneal cavity but not in bone marrow, blood, spleen, or liver. In AT of CCR2(-/-) mice, an increased eosinophil number positively correlated with M2-like macrophages, expression of the Treg marker Foxp3, and type 2 cytokines, Il4, Il5, and Il13. This is the first study to link CCR2 function with regulation of AT eosinophil accumulation. PMID:25934927

  8. Acute Leukemias in Children

    PubMed Central

    Pai, Mohan K. R.

    1979-01-01

    With combination chemotherapy approximately 50% of children with lymphoblastic leukemia survive for five or more years and it is now realistic to hope for a cure. Development of sophisticated cytochemical and immunological techniques have enabled us to recognize the factors that predispose to treatment failures. The survival in acute non-lymphocytic leukemia continues to be poor despite the introduction of several innovative treatment regimens. Current research is focused on the manipulation of the host-tumor immune response to eradicate the disease by treatment modalities such as immunotherapy and bone marrow transplantation. Since the treatment regimens are becoming more complex, the initial diagnosis and treatment is best carried out at centres specialized in the management of childhood malignancies. ImagesFig. 1Fig. 2Fig. 3 PMID:21297755

  9. 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. PMID:23243287

  10. 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)

  11. Elevated IL-33 expression is associated with pediatric eosinophilic esophagitis, and exogenous IL-33 promotes eosinophilic esophagitis development in mice.

    PubMed

    Judd, L M; Heine, R G; Menheniott, T R; Buzzelli, J; O'Brien-Simpson, N; Pavlic, D; O'Connor, L; Al Gazali, K; Hamilton, O; Scurr, M; Collison, A M; Mattes, J; Allen, K J; Giraud, A S

    2016-01-01

    We tested whether the T helper (Th) type 2 (Th2) cell agonist and allergenic ligand IL-33 was associated with eosinophilic esophagitis (EoE) development in a pediatric cohort and whether IL-33 protein could induce disease symptoms in mice. Biopsies from EoE patients or controls were used to measure IL-33 mRNA and protein expression. Increased expression of IL-33 mRNA was found in the esophageal mucosa in EoE. IL-33 protein was detected in cells negative for CD45, mast cells, and epithelial cell markers near blood vessels. Circulating levels of IL-33 were not increased. The time course for IL-33 gene expression was quantified in an established Aspergillus fumigatus allergen mouse model of EoE. Because IL-33 induction was transient in this model and chronicity of IL-33 expression has been demonstrated in humans, naive mice were treated with recombinant IL-33 for 1 wk and esophageal pathology was evaluated. IL-33 application produced changes consistent with phenotypically early EoE, including transmural eosinophilia, mucosal hyperproliferation, and upregulation of eosinophilic genes and chemokines. Th2 cytokines, including IL-13, along with innate lymphoid cell group 2, Th1/17, and M2 macrophage marker genes, were increased after IL-33 application. IL-33-induced eosinophilia was ablated in IL-13 null mice. In addition, IL-33 induced a profound inhibition of the regulatory T cell gene signature. We conclude that IL-33 gene expression is associated with pediatric EoE development and that application of recombinant protein in mice phenocopies the early clinical phase of the human disease in an IL-13-dependent manner. IL-33 inhibition of esophageal regulatory T cell function may induce loss of antigenic tolerance, thereby providing a mechanistic rationale for EoE development. PMID:26514775

  12. Urinary Eosinophil Protein X in Childhood Asthma: Relation with Changes in Disease Control and Eosinophilic Airway Inflammation

    PubMed Central

    Nuijsink, Marianne; Hop, Wim C. J.; Sterk, Peter J.; Duiverman, Eric J.; De Jongste, Johan C.

    2013-01-01

    The aim of this study was to assess cross-sectional and longitudinal correlations between uEPX and other markers of asthma control and eosinophilic airway inflammation. Methods. We measured uEPX at baseline, after 1?year and after 2?years in 205 atopic asthmatic children using inhaled fluticasone. At the same time points, we assessed symptom scores (2 weeks diary card), lung function (forced expiratory volume in one second (FEV1)), airway hyperresponsiveness (AHR), and percentage eosinophils in induced sputum (% eos). Results. We found negative correlations between uEPX and FEV1 at baseline (r = ?0.18, P = 0.01), after 1 year (r = ?0.25, P < 0.01) and after 2 years (r = ?0.21, P = 0.02). Within-patient changes of uEPX showed a negative association with FEV1 changes (at 1?year: r = ?0.24, P = 0.01; at 2?years: r = ?0.21, P = 0.03). Within-patient changes from baseline of uEPX correlated with changes in % eos. No relations were found between uEPX and symptoms. Conclusion. In this population of children with atopic asthma, uEPX correlated with FEV1 and % eos, and within-subjects changes in uEPX correlated with changes in FEV1 and % eos. As the associations were weak and the scatter of uEPX wide, it seems unlikely that uEPX will be useful as a biomarker for monitoring asthma control in the individual child. PMID:23401643

  13. Epigenetic mechanisms in leukemia.

    PubMed

    Zaidi, Sayyed K; Trombly, Daniel J; Dowdy, Christopher R; Lian, Jane B; Stein, Janet L; van Wijnen, Andre J; Stein, Gary S

    2012-09-01

    Focal organization of regulatory machinery within the interphase nucleus is linked to biological responsiveness and perturbed in cancer. Lineage determinant Runx proteins organize and assemble multi-protein complexes at sites of transcription within the nucleus and regulate both RNA polymerase II- and I-mediated gene expression. In addition, Runx proteins epigenetically control lineage determining transcriptional programs including: 1) architectural organization of macromolecular complexes in interphase, 2) regulation of gene expression through bookmarking during mitosis, and 3) microRNA-mediated translational control in the interphase nucleus. These mechanisms are compromised with the onset and progression of cancer. For example, the oncogenic AML1-ETO protein, which results from a chromosomal translocation between chromosomes 8 and 21, is expressed in nearly 25% of all acute myelogenous leukemias, disrupts Runx1 subnuclear localization during interphase and compromises transcriptional regulation. Epigenetically, the leukemic protein redirects the Runx1 DNA binding domain to leukemia-specific nuclear microenvironments, modifies regulatory protein accessibility to Runx1 target genes by imprinting repressive chromatin marks, and deregulates the microRNA (miR) profile of diseased myeloid cells. Consequently, the entire Runx1-dependent transcriptional program of myeloid cells is deregulated leading to onset and progression of acute myeloid leukemia and maintenance of leukemic phenotype. We discuss the potential of modified epigenetic landscape of leukemic cells as a viable therapeutic target. PMID:22884030

  14. 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

  15. EOSINOPHIL INFLUX TO THE NASAL AIRWAY FOLLOWING LOCAL, LOW-LEVEL LPS CHALLENGE IN HUMANS

    EPA Science Inventory

    Background: Recent obervations show that atopic asthmatic subjects have increased sensitivity to respirable endotoxin (or LPS) compared with normal persons. In vitro studies demonstrate that LPS enchances eosinophil survival. These obervations suggest that the effects of inhal...

  16. Expect the Unexpected: A Case of Isolated Eosinophilic Meningitis in Toxocariasis

    PubMed Central

    Sick, Christian; Hennerici, Michael G.

    2014-01-01

    We present the case of a young police officer suffering from headache without other neurological symptoms caused by isolated eosinophilic meningitis, which resulted from an infection with Toxocara cati, along with a discussion of the differential diagnosis. PMID:25535488

  17. [Determining asthma treatment in children by monitoring fractional exhaled nitric oxide, sputum eosinophils and leukotriene B].

    PubMed

    Vizmanos-Lamotte, G; Cruz, M J; G籀mez-Oll矇s, S; Mu簽oz, X; de Mir Messa, I; Moreno-Gald籀, A

    2015-01-01

    Sputum eosinophils and exhaled fractional nitric oxide (FENO) are markers of airway inflammation in asthma. Cytokines, cysteinyl-leukotrienes and leukotriene B4 (LTB4) are responsible for this inflammation. The aim of this study is to determine the usefulness of these markers in monitoring asthma treatment in children. FENO, sputum eosinophils, and LTB4 in induced sputum were performed in 10 children (9-15 years old). These determinations were repeated four months later, after the beginning or an increase in the treatment. FENO values tended to decrease (P=.15), pulmonary function tended to improve (P=.10), and sputum eosinophils decreased (P=.003) compared to the first determination. There were no differences in LTB4 concentrations (P=.88). Sputum eosinophils seem to be more precise than FENO in the monitoring of inflammation in asthmatic children. PMID:24857428

  18. Eosinophil recruitment to nasal nerves after allergen challenge in allergic rhinitis.

    PubMed

    Thornton, Margaret A; Akasheh, Nadim; Walsh, Marie-Therese; Moloney, Michael; Sheahan, Patrick O; Smyth, Claire M; Walsh, Rory McConn; Morgan, Ross M; Curran, David R; Walsh, Michael T; Gleich, Gerald J; Costello, Richard W

    2013-04-01

    In allergen challenged animal models, eosinophils localize to airway nerves leading to vagally-mediated hyperreactivity. We hypothesized that in allergic rhinitis eosinophils recruited to nasal nerves resulted in neural hyperreactivity. Patients with persistent allergic rhinitis (n=12), seasonal allergic rhinitis (n=7) and controls (n=10) were studied. Inferior nasal turbinate biopsies were obtained before, 8 and 48h after allergen challenge. Eight hours after allergen challenge eosinophils localized to nerves in both rhinitis groups; this was sustained through 48h. Bradykinin challenge, with secretion collection on the contralateral side, was performed to demonstrate nasal nerve reflexes. Twenty fourhours after allergen challenge, bradykinin induced a significant increase in secretions, indicating nasal hyperreactivity. Histological studies showed that nasal nerves expressed both vascular cell adhesion molecule-1 (VCAM-1) and chemokine (C-C motif) ligand 26 (CCL-26). Hence, after allergen challenge eosinophils are recruited and retained at nerves and so may be a mechanism for neural hyperreactivity. PMID:23518598

  19. Endoscopic findings and pathologic characteristics of gastric eosinophilic granuloma: A report of 18 patients

    PubMed Central

    Song, Wen-Chong; Yu, Jie-Ping; Shen, Lei; Xia, Hong; Luo, He-Sheng

    2006-01-01

    AIM: To investigate the endoscopic findings and patholo-gic characteristics of gastric eosinophilic granuloma (GEG). METHODS: A retrospective study of 18 cases of gastric eosinophilic granulomas was conducted. Gastroscopy was performed and all specimens of biopsies were stained by H&E and observed under light microscopy. RESULTS: Ulcer was the most frequent endoscopic appearance. The others included deformed pylorus and/or duodenal bulb, esophagitis, mucous hyperemia and/or mucosal erosion. Eosinophilic cell infiltration and generous hyperplasia of arterioles, venules and lymph vessels were found in the lesions of the patients. Interstitium had massive eosinophilic infiltrates and was made up of collagen fibers and fibroblasts. Lymphoid follicles were revealed in some sections of biopsies. CONCLUSION: GEG is lack of specific symptoms and physical signs. It can be misdiagnosed as gastric ulcer in most cases before biopsies. Endoscopy and endoscopic multiple deep biopsies in suspected areas are indispensable for correct diagnosis of GEG. PMID:17167848

  20. Piecemeal degranulation in human eosinophils: a distinct secretion mechanism underlying inflammatory responses.

    PubMed

    Melo, Rossana C N; Weller, Peter F

    2010-10-01

    Secretion is a fundamental cell process underlying different physiological and pathological events. In cells from the human immune system such as eosinophils, secretion of mediators generally occurs by means of piecemeal degranulation, an unconventional secretory pathway characterized by vesicular transport of small packets of materials from the cytoplasmic secretory granules to the cell surface. During piecemeal degranulation in eosinophils, a distinct transport vesicle system, which includes large, pleiomorphic vesiculo-tubular carriers is mobilized and enables regulated release of granule-stored proteins such as cytokines and major basic protein. Piecemeal degranulation underlies distinct functions of eosinophils as effector and immunoregulatory cells. This review focuses on the structural and functional advances that have been made over the last years concerning the intracellular trafficking and secretion of eosinophil proteins by piecemeal degranulation during inflammatory responses. PMID:20712018

  1. Histopathologic study of eosinophilic bronchointerstitial pneumonia caused by Crenosoma striatum in the hedgehog.

    PubMed

    Hoseini, Seyed Mohammad; Youssefi, Mohammad Reza; Mousapour, Aliasghar; Dozouri, Rohollah; Eshkevari, Shahab Ramezanpour; Nikzad, Mohammad; Nikzad, Reza; Omidzahir, Shila

    2014-06-01

    Crenosoma striatum is a species of parasitic nematodes from the family Crenosomatidae responsible for pathologic lung lesions in the hedgehog (Erinaceus europaeus). Infection with C. striatum can cause weight loss, dry cough, and bronchitis. In the present study, hedgehogs killed by road accidents, or trapped and found dead on farms in different parts of Mazandaran province (Iran), were transferred to the laboratory. After dissection, parasite samples collected from the lung were placed into 70% alcohol. After clarification with lactophenol and subsequent staining, the nematodes were identified as C. striatum according to previously published guidelines. For histopathologic examination, lung samples were collected. The tissues were fixed and following routine processing, sections were stained with hematoxylin and eosin. Microscopic diagnoses included hyperemia, eosinophilic bronchointerstitial pneumonia, thickening of the interstitium, and eosinophilic microabscesses in bronchial airways. Eosinophilic pneumonia was characterized by eosinophil and other mononuclear leukocyte infiltration within the lung interstitium. Crenosoma striatum can lead to mortality in hedgehogs. PMID:25000695

  2. Studies on eosinophil leucocyte migration. II. Factors specifically chemotactic for eosinophils and neutrophils generated from guinea-pig serum by antigenantibody complexes

    PubMed Central

    Kay, A. B.

    1970-01-01

    Chemotactic activity for eosinophils and neutrophils has been studied using guinea-pig serum activated by preformed antigenantibody complexes. Rabbit complexes or complexes prepared either with guinea-pig IgG2 or IgG1 were equally capable of generating a heat stable activity from guinea-pig serum that was chemotactic for guinea-pig eosinophils and for neutrophils of both the guinea-pig and the rabbit. This was distinguished from a relatively heat-labile chemotactic activity present in untreated guinea-pig serum. The heat-stable complex-mediated chemotactic activity was thought to be complement dependent since chemotaxis for eosinophils or neutrophils could not be generated from heated serum, ammonia treated serum or from serum treated with complexes in the presence of 001 M EDTA. Guinea-pig sera, activated either with rabbit, guinea-pig IgG1 or IgG2 complexes, was fractionated by sucrose-density gradient ultracentrifugation and by Sephadex chromatography. In all experiments two peaks of cell specific chemotactic activity could be separated. The peak of activity for guinea-pig neutrophils was approximately 45S and in the fractionation range of proteins having a molecular weight of between 65,000 and 85,000. The peak of guinea-pig eosinophil chemotactic activity was 15S2S and in the molecular weight range of between 15,000 and 20,000. Those fractions which were chemotactic for guinea-pig neutrophils did not attract rabbit neutrophils. Rabbit neutrophils migrated towards those fractions of guinea-pig serum chemotactic for guinea-pig eosinophils; therefore, the properties associated with guinea-pig eosinophil chemotactic activity were similar to previously published data for a fragment cleaved from the 5th component of complement. ImagesFig. 2Fig. 3 PMID:4992784

  3. [Difficulties in the diagnosis of prolonged pulmonary eosinophilic infiltration in a child].

    PubMed

    Murgoci, G

    1993-01-01

    The paper deals with a 6-year-old child admitted to hospital for prolonged febrile syndrome, hemoptic sputum with radiological persistence of some pulmonary opacities which raised many hypotheses concerning the etiological diagnosis. A prolonged eosinophilic pulmonary infiltrate due to an infestation with Ascaris lumbricoides and Giardia was the matter in the study case. The specific anti-parasitic treatment has a decisive role in the clinical radiological improvement in case of a parasitic eosinophilic lung. PMID:7950452

  4. Combination of CD157 and FLAER to Detect Peripheral Blood Eosinophils by Multiparameter Flow Cytometry.

    PubMed

    Carulli, Giovanni; Marini, Alessandra; Sammuri, Paola; Domenichini, Cristiana; Ottaviano, Virginia; Pacini, Simone; Petrini, Mario

    2015-01-01

    The identification of eosinophils by flow cytometry is difficult because most of the surface antigens expressed by eosinophils are shared with neutrophils. Some methods have been proposed, generally based on differential light scatter properties, enhanced autofluorescence, lack of CD16 or selective positivity of CD52. Such methods, however, show several limitations. In the present study we report a novel method based on the analysis of glycosylphosphatidylinositol (GPI)-linked molecules. The combination of CD157 and FLAER was used, since FLAER recognizes all GPI-linked molecules, while CD157 is absent on the membrane of eosinophils and expressed by neutrophils. Peripheral blood samples from normal subjects and patients with variable percentages of eosinophils (n = 31), and without any evidence for circulating immature myeloid cells, were stained with the combination of FLAER-Alexa Fluor and CD157-PE. A FascCanto II cytometer was used. Granulocytes were gated after CD33 staining and eosinophils were identified as CD157(-)/FLAER(+) events. Neutrophils were identified as CD157(+)/FLAER(+) events. The percentages of eosinophils detected by this method showed a very significant correlation both with automated counting and with manual counting (r = 0.981 and 0.989, respectively). Sorting assays were carried out by a S3 Cell Sorter: cytospins obtained from CD157(-)/FLAER(+) events consisted of 100% eosinophils, while samples from CD157(+)/FLAER(+) events were represented only by neutrophils. In conclusion, this method shows high sensitivity and specificity in order to distinguish eosinophils from neutrophils by flow cytometry. However, since CD157 is gradually up-regulated throughout bone marrow myeloid maturation, our method cannot be applied to cases characterized by immature myeloid cells. PMID:26490516

  5. Eosinophilic fasciitis: typical abnormalities, variants and differential diagnosis of fasciae abnormalities using MR imaging.

    PubMed

    Kirchgesner, T; Dallaudi鋨e, B; Omoumi, P; Malghem, J; Vande Berg, B; Lecouvet, F; Houssiau, F; Galant, C; Larbi, A

    2015-04-01

    Eosinophilic fasciitis is a rare condition. It is generally limited to the distal parts of the arms and legs. MRI is the ideal imaging modality for diagnosing and monitoring this condition. MRI findings typically evidence only fascial involvement but on a less regular basis signal abnormalities may be observed in neighboring muscle tissue and hypodermic fat. Differential diagnosis of eosinophilic fasciitis by MRI requires the exclusion of several other superficial and deep soft tissue disorders. PMID:25746223

  6. An unusual cause of terminal hematuria in a child: Eosinophilic cystitis

    PubMed Central

    畤do?an, Elif Bahat; Arslansoyu ドmlar, Se蓾l; Bilen, Sevcan; ?mamo?lu, Mustafa; T?ra?, ?kran; Cansu, Ay?egl; 畤oran, Yavuz

    2014-01-01

    Eosinophilic cystitis is a rare inflammatory disease of the bladder; it rarely occurs in children. Patients typically show irritative urination symptoms frequently, with a possible need for urgency, alongside dysuria, gross haematuria, suprapubic pain and painful urination. Sometimes bladder mass accumulation with the possibility of malignancy is also observed. We present an 8-year-old male patient who gained admission for terminal hematuria and discuss the management of eosinophilic cystitis. PMID:25485018

  7. Characterization of the relationship between dose and blood eosinophil response following subcutaneous administration of mepolizumab

    PubMed Central

    Pouliquen, Isabelle J.; Kornmann, Oliver; Barton, Sharon V.; Price, Jeffrey A.; Ortega, Hector G.

    2015-01-01

    Objective: Mepolizumab is a humanized IgG1 monoclonal antibody that blocks human IL-5 from binding to the IL-5 receptor, which is mainly expressed on eosinophils. Eosinophils are key cells in the inflammatory cascade of various diseases, including asthma. This study investigated the pharmacokinetic (PK)/pharmacodynamic (PD) relationship between exposure of mepolizumab subcutaneous (SC) administration and blood eosinophil reduction compared with intravenous (IV) administration in adult subjects with asthma. Methods: In this multi-center, randomized, open-label, parallel-group, repeat-dose study, 70 adult subjects received one of four possible treatment regimens: mepolizumab 12.5, 125, or 250 mg SC or 75 mg IV. In addition to analyzing the dose and PK/PD relationship, absolute bioavailability, safety, tolerability, and incidence of anti-mepolizumab antibodies were evaluated. Results: Blood eosinophil levels decreased in a dose-dependent manner with the lowest (12.5mg) dose clearly differentiating from the other doses. A non-linear inhibition Imax model based on blood eosinophil levels at week 12 identified that the SC doses providing 50% and 90% of maximal blood eosinophil inhibition were 11mg (95% confidence interval (CI): 5.19 16.85) and 99mg (95% CI: 47 152), respectively. The route of administration did not affect the exposure-response relationship. The estimated mepolizumab SC absolute bioavailability (arm) was 74% (90% CI: 54102%). The safety profile of mepolizumab was favorable. Conclusions: A dose-dependent reduction in blood eosinophils across all mepolizumab doses investigated was observed. The subcutaneous absolute bioavailability was 74%. The route of administration did not affect the mepolizumab exposure eosinophil response relationship. PMID:26445140

  8. Accumulation of eosinophils, mast cells, and basophils in the spleen in anaphylactic deaths.

    PubMed

    Edston, Erik

    2013-12-01

    Death in anaphylactic shock cannot be diagnosed by autopsy alone. Morphological diagnosis of anaphylactic death by counting mast cells in the lung and airways have failed to give consistent results. Previously it has been observed that eosinophils seem to accumulate in the spleen in anaphylaxis. The purpose of this study was to investigate if it is possible to safely diagnose anaphylactic deaths by counting eosinophils, mast cells, and basophils in the spleen. In 43 forensic autopsy cases specific antibodies to mast cells, eosinophil-, and basophil granulocytes were used on sections from lung and splenic tissue. The cells were counted in 20 40 fields in a Leica photo-microscope. Presumed deaths in anaphylaxis were compared with sudden deaths after intravenous injection of opiates, and sudden cardiac deaths (control group). The main result was that significant (p < 0.05) increases of both eosinophil granulocytes (mean 26.6 簣 17.8/SD/)and mast cells (3.2 簣 2.0/SD/) versus controls (eosinophils mean 7.0 簣 10.5 and mast cells mean 0.9 簣 1.1) were seen in splenic tissue in anaphylactic deaths. Comparing cases with high and low concentrations of mast cell tryptase in serum showed a similar increase in eosinophils and mast cells in the spleen in cases with elevated tryptase, but not in the lung. The numbers of pulmonary mast cells and eosinophils were not different in anaphylactic deaths compared with controls. It is concluded that by quantifying eosinophil granulocytes and mast cells in the spleen in combination with tryptase measurements in serum it is possible to diagnose anaphylaxis with a high degree of certainty. PMID:23839665

  9. Electron tomography and immunonanogold electron microscopy for investigating intracellular trafficking and secretion in human eosinophils.

    PubMed

    Melo, Rossana C N; Dvorak, Ann M; Weller, Peter F

    2008-08-01

    Electron tomography (ET) has increasingly been used to understand the complexity of membrane systems and protein-trafficking events. By ET and immunonanogold electron microscopy, we recently defined a route for vesicular transport and release of granule-stored products from within activated human eosinophils, cells specialized in the secretion of numerous cytokines and other proteins during inflammatory responses. Here, we highlight these techniques as important tools to unveil a distinct eosinophil vesicular system and secretory pathway. PMID:18410520

  10. c-FLIP Protects Eosinophils from TNF-?-Mediated Cell Death In Vivo

    PubMed Central

    Gordy, Claire; Liang, Jie; Pua, Heather; He, You-Wen

    2014-01-01

    Understanding the signals that regulate eosinophil survival and death is critical to developing new treatments for asthma, atopy, and gastrointestinal disease. Previous studies suggest that TNF-? stimulation protects eosinophils from apoptosis, and this TNF-?-mediated protection is mediated by the upregulation of an unknown protein by NF-?B. Here, we show for the first time that eosinophils express the caspase 8-inhibitory protein c-FLIP, and c-FLIP expression is upregulated upon TNF-? stimulation. Considering that c-FLIP expression is regulated by NF-?B, we hypothesized that c-FLIP might serve as the molecular switch that converts TNFRI activation to a pro-survival signal in eosinophils. Indeed, we found that one c-FLIP isoform, c-FLIPL, is required for mouse eosinophil survival in the presence of TNF-? both in vitro and in vivo. Importantly, our results suggest c-FLIP as a potential therapeutic target for the treatment of eosinophil-mediated disease. PMID:25333625

  11. Fatal eosinophilic myocarditis develops in the absence of IFN? and IL17A

    PubMed Central

    Barin, Jobert G.; Baldeviano, G. Christian; Talor, Monica V.; Wu, Lei; Ong, SuFey; Fairweather, DeLisa; Bedja, Djahida; Stickel, Natalie R.; LeGault, Jillian A.; Cardamone, Ashley B.; Zheng, Dongfeng; Gabrielson, Kathleen L.; Rose, Noel R.; Cihakova, Daniela

    2014-01-01

    CD4+ T cells play a central role in inflammatory heart disease, implicating a cytokine product associated with helper T cell effector function as a necessary mediator of this pathophysiology. IFN?-deficient mice developed severe autoimmune myocarditis (EAM), in which mice are immunized with cardiac myosin peptide, while IL17A-deficient mice were protected from progression to dilated cardiomyopathy. We generated IFN??/?IL17A?/? mice to assess whether IL17 signaling was responsible for the severe EAM of IFN??/? mice. Surprisingly, IFN??/?IL17A?/? mice developed a rapidly fatal EAM. Eosinophils comprised a third of infiltrating leukocytes, qualifying this disease eosinophilic myocarditis. We found increased cardiac production of CCL11/eotaxin, and Th2 deviation among heart-infiltrating CD4+ cells. Ablation of eosinophil development improved survival of IFN??/?IL17A?/? mice, demonstrating the necessity of eosinophils in fatal heart failure. The severe and rapidly fatal autoimmune inflammation that developed in the combined absence of IFN? and IL17A constitutes a novel model of eosinophilic heart disease in humans. This is also the first demonstration that eosinophils have the capacity to act as necessary mediators of morbidity in an autoimmune process. PMID:24048893

  12. Fatal eosinophilic myocarditis develops in the absence of IFN-? and IL-17A.

    PubMed

    Barin, Jobert G; Baldeviano, G Christian; Talor, Monica V; Wu, Lei; Ong, SuFey; Fairweather, DeLisa; Bedja, Djahida; Stickel, Natalie R; Fontes, Jillian A; Cardamone, Ashley B; Zheng, Dongfeng; Gabrielson, Kathleen L; Rose, Noel R; Cih嫜ov, Daniela

    2013-10-15

    CD4(+) T cells play a central role in inflammatory heart disease, implicating a cytokine product associated with Th cell effector function as a necessary mediator of this pathophysiology. IFN-?-deficient mice developed severe experimental autoimmune myocarditis (EAM), in which mice are immunized with cardiac myosin peptide, whereas IL-17A-deficient mice were protected from progression to dilated cardiomyopathy. We generated IFN-?(-/-)IL-17A(-/-) mice to assess whether IL-17 signaling was responsible for the severe EAM of IFN-?(-/-) mice. Surprisingly, IFN-?(-/-)IL-17A(-/-) mice developed a rapidly fatal EAM. Eosinophils constituted a third of infiltrating leukocytes, qualifying this disease as eosinophilic myocarditis. We found increased cardiac production of CCL11/eotaxin, as well as Th2 deviation, among heart-infiltrating CD4(+) cells. Ablation of eosinophil development improved survival of IFN-?(-/-)IL-17A(-/-) mice, demonstrating the necessity of eosinophils in fatal heart failure. The severe and rapidly fatal autoimmune inflammation that developed in the combined absence of IFN-? and IL-17A constitutes a novel model of eosinophilic heart disease in humans. This is also, to our knowledge, the first demonstration that eosinophils have the capacity to act as necessary mediators of morbidity in an autoimmune process. PMID:24048893

  13. An experimental study of inner ear injury in an animal model of eosinophilic otitis media

    PubMed Central

    Nishizawa, Hisanori; Kurose, Akira; Nakagawa, Takashi; Takahata, Junko; Sasaki, Akira

    2014-01-01

    Conclusion: As the periods of intratympanic injection of ovalbumin (OVA) to the middle ear became longer, marked eosinophil infiltration in the perilymphatic space was observed. Moreover severe morphological damage of the organ of Corti was observed in the 28-day antigen-stimulation side. These results indicate that eosinophilic inflammation occurred in the inner ear and caused profound hearing loss. Objective: The purpose of the present study was to elucidate the inner ear damage in a new animal model of eosinophilic otitis media (EOM) which we recently constructed. Methods: We constructed the animal model of EOM by intraperitoneal and intratympanic injection of OVA. Infiltrating cells and the inner ear damage were examined by histological study. Results: In the inner ear, a few eosinophils were seen in the scala tympani of the organ of Corti and the dilation of capillaries of the stria vascularis was observed in the 7-day stimulation side. In the 14-day antigen stimulation side, some eosinophils and macrophages were seen in not only the scala tympani but also the scala vestibule. In the 28-day antigen-stimulation side, severe morphological damage of the organ of Corti and many eosinophils, red blood cells, and plasma cells infiltrating the perilymph were observed. PMID:24359096

  14. Activated eosinophils in association with enteric nerves in inflammatory bowel disease.

    PubMed

    Smyth, Claire M; Akasheh, Nadim; Woods, Sara; Kay, Elaine; Morgan, Ross K; Thornton, Margaret A; O'Grady, Anthony; Cummins, Robert; Sheils, Orla; Smyth, Peter; Gleich, Gerald J; Murray, Frank M; Costello, Richard W

    2013-01-01

    Enteric neural dysfunction leads to increased mucous production and dysmotility in inflammatory bowel disease (IBD). Prior studies have shown that tissue eosinophilia is related to disease activity. We hypothesized that interactions between eosinophils and nerves contribute to neural dysfunction in IBD. Tissue from patients with intractable IBD, endoscopic biopsies from patients with steroid responsive IBD, both when active and quiescent, and control tissue were studied. Immunohistochemical studies showed that eosinophils localize to nerves in the mucosal layer of patients with Crohn's disease (CD) (p<0.001) and ulcerative colitis (UC), (p<0.01). Eosinophils localized to substance P and choline acetyltransferase (ChAT) immunostained nerves. Real time PCR of laser capture micro-dissected enteric ganglia demonstrated Intercellular Adhesion Molecule 1 (ICAM-1) mRNA was increased 7-fold in UC (n?=?4), (p?=?0.03), and 10-fold in CD (n?=?3), (p?=?0.05). Compared with controls, eotaxin-3 (CCL-26) mRNA was increased 9-fold in UC (p?=?0.04) and 15-fold in CD (p?=?0.06). Eosinophil numbers correlated with disease activity, while deposition of major basic protein (MBP) and eosinophil Transforming Growth Factor ?-1 (TGF?-1) expression were seen in therapeutically responsive disease. These data indicate a significant localization of eosinophils to nerves in IBD, mediated through neurally expressed ICAM-1 and eotaxin-3. This cell/neural interaction may influence the function of nerves and contribute to symptoms in IBD. PMID:23717571

  15. Activated Eosinophils in Association with Enteric Nerves in Inflammatory Bowel Disease

    PubMed Central

    Smyth, Claire M.; Akasheh, Nadim; Woods, Sara; Kay, Elaine; Morgan, Ross K.; Thornton, Margaret A.; OGrady, Anthony; Cummins, Robert; Sheils, Orla; Smyth, Peter; Gleich, Gerald J.; Murray, Frank M.; Costello, Richard W.

    2013-01-01

    Enteric neural dysfunction leads to increased mucous production and dysmotility in inflammatory bowel disease (IBD). Prior studies have shown that tissue eosinophilia is related to disease activity. We hypothesized that interactions between eosinophils and nerves contribute to neural dysfunction in IBD. Tissue from patients with intractable IBD, endoscopic biopsies from patients with steroid responsive IBD, both when active and quiescent, and control tissue were studied. Immunohistochemical studies showed that eosinophils localize to nerves in the mucosal layer of patients with Crohns disease (CD) (p<0.001) and ulcerative colitis (UC), (p<0.01). Eosinophils localized to substance P and choline acetyltransferase (ChAT) immunostained nerves. Real time PCR of laser capture micro-dissected enteric ganglia demonstrated Intercellular Adhesion Molecule 1 (ICAM-1) mRNA was increased 7-fold in UC (n?=?4), (p?=?0.03), and 10-fold in CD (n?=?3), (p?=?0.05). Compared with controls, eotaxin-3 (CCL-26) mRNA was increased 9-fold in UC (p?=?0.04) and 15-fold in CD (p?=?0.06). Eosinophil numbers correlated with disease activity, while deposition of major basic protein (MBP) and eosinophil Transforming Growth Factor ? -1 (TGF?-1) expression were seen in therapeutically responsive disease. These data indicate a significant localization of eosinophils to nerves in IBD, mediated through neurally expressed ICAM-1 and eotaxin-3. This cell/neural interaction may influence the function of nerves and contribute to symptoms in IBD. PMID:23717571

  16. Uterine type II estrogen-binding sites are not of eosinophil origin

    SciTech Connect

    Not Available

    1986-01-05

    A recent report suggested that nuclear type II sites in the rat uterus are of eosinophil origin and may represent (/sup 3/H)estradiol binding to eosinophil peroxidase. To further evaluate this hypothesis the authors examined the response of nuclear type II sites to estrogen under conditions where eosinophils are not present. Results of the experiments show that physiological levels of estradiol-17..beta.. (10 nM for 72 h) will stimulate nuclear type II sites in highly purified cultures of rat uterine stromal and myometrial cells. The magnitude of the response of type II sites to estradiol in these stromal (4-fold) and myometrial (80-fold) cell cultures was essentially identical to that observed in the uterine cell types following in vivo estrogen treatment. Since these highly purified cultures of uterine cells were prepared from the uterus of a 21-day ovariectomized rat which is devoid of eosinophils, it was concluded that estradiol stimulation of nuclear type II sites is a direct intracellular response to estrogen which occurs independent of eosinophil accumulation. Furthermore, it was found that type II sites in the rat uterus are not peroxidase. Stimulation of cytosol and nuclear type II sites by estrogen in the rat uterus is a direct intracellular response to the hormone unrelated to eosinophil accumulation and/or peroxidase activity.

  17. Toxicity of eosinophil MBP is repressed by intracellular crystallization and promoted by extracellular aggregation.

    PubMed

    Soragni, Alice; Yousefi, Shida; Stoeckle, Christina; Soriaga, Angela B; Sawaya, Michael R; Kozlowski, Evelyne; Schmid, In鋊; Radonjic-Hoesli, Susanne; Boutet, Sebastien; Williams, Garth J; Messerschmidt, Marc; Seibert, M Marvin; Cascio, Duilio; Zatsepin, Nadia A; Burghammer, Manfred; Riekel, Christian; Colletier, Jacques-Philippe; Riek, Roland; Eisenberg, David S; Simon, Hans-Uwe

    2015-03-19

    Eosinophils are white blood cells that function in innate immunity and participate in the pathogenesis of various inflammatory and neoplastic disorders. Their secretory granules contain four cytotoxic proteins, including the eosinophil major basic protein (MBP-1). How MBP-1 toxicity is controlled within theeosinophil itself and activated upon extracellular release is unknown. Here we show how intragranular MBP-1 nanocrystals restrain toxicity, enabling its safe storage, and characterize them with an X-ray-free electron laser. Following eosinophil activation, MBP-1 toxicity is triggered by granule acidification, followed by extracellular aggregation, which mediates the damage to pathogens and host cells. Larger non-toxic amyloid plaques are also present in tissues of eosinophilic patients in a feedback mechanism that likely limits tissue damage under pathological conditions of MBP-1 oversecretion. Our results suggest that MBP-1 aggregation is important for innate immunity and immunopathology mediated by eosinophils and clarify how its polymorphic self-association pathways regulate toxicity intra- and extracellularly. PMID:25728769

  18. Eosinophilic myocarditis in CBA/J mice infected with Toxocara canis.

    PubMed Central

    Cookston, M.; Stober, M.; Kayes, S. G.

    1990-01-01

    In humans, chronic eosinophilia has been associated clinically with endomyocardial fibrosis and myocardial damage. Mice infected with Toxocara canis have a marked eosinophilia, and develop eosinophil-rich granulomatous lesions in the soft tissues of the body, especially the lungs, liver, brain, and skeletal muscle. Few reports have described myocardial lesions associated with T. canis infections in mice. We examined the hearts of CBA/J mice killed at weekly intervals over an 8-week period for evidence of myocardial damage that might be attributable to eosinophils. Total white blood cell counts and eosinophil counts were obtained during this period, and revealed a peak white blood cell count of approximately 28,000 cells/mm3 at day 7 after infection and a peak eosinophil count of approximately 4,000 cells/mm3 at day 14 after infection. Myocardial lesions in the ventricular wall began as focal infiltrates of eosinophils and histiocytes, then progressed into granulomata containing necrotic debris. Collagen deposition was noted by day 21 after infection. By day 42 after infection, the lesions had contracted greatly because of a loss of cellularity, and consisted mainly of fibroblasts and hemosiderin-laden macrophages. Myocyte damage, characterized by increased eosinophilia and necrosis, was observed. T. canis-infected CBA/J mice thus offer a useful model to study eosinophil-dependent myocardial damage. Images Figure 3 Figure 4 Figure 5 Figure 6 Figure 7 Figure 8 PMID:2349964

  19. 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

  20. 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

  1. Eosinophilic esophagitis: perspectives of adult and pediatric gastroenterologists.

    PubMed

    King, Jeremy; Khan, Seema

    2010-04-01

    To survey pediatric (PGI) and adult gastroenterologists (AGI) regarding their perceptions about the etiology, diagnosis, and management of eosinophilic esophagitis (EoE), and to assess whether differences in the clinical approach to EoE exist between these subspecialists. A 21-item survey related to EoE was emailed to PGI who subscribe to the PEDSGI Bulletin Board, and to two AGI per Electoral College vote in the US, randomly selected from each state. The survey was voluntary, and consent was assumed based on survey submission. The responses were submitted anonymously and results compiled in a secure Web site. A total of 249 physicians from across the globe responded to the survey, 68% of whom were PGI. The majority of respondents worked primarily in an academic institution or teaching hospital. Respondents revealed diagnosing an average of six cases (median 8, range 0-30) of EoE in the past 6 months. Ninety-two percent of AGI who see a patient with dysphagia and suspected EoE proceed to endoscopy with biopsies, compared to only 54% of PGI (P < 0.05); 38% of PGI would first perform an upper GI study. Both subspecialties agreed that biopsies of the proximal and distal esophagus are needed to make a definitive diagnosis of EoE. Fifty-eight percent PGI and 44% AGI defined EoE as an eosinophilic density of > or =20 per high power field (hpf) in esophageal biopsies. Seventy-seven percent of PGI but only 16% of AGI reported routine referral of patients for food allergy evaluation (P < 0.05). While 77% PGI and 91% of AGI would rely on a symptom-based follow-up, 27% PGI versus 9% AGI follow patients with biopsies according to a pre-determined schedule and another 38% repeat biopsies as needed, versus 15% AGI. This survey exposes a few inconsistencies among gastroenterologists in the diagnosis, management, and follow-up of patients with EoE. The currently available practice guidelines for the diagnosis and management of EoE are largely based on retrospective studies and expert opinion. The results of this survey suggest that a collaborative effort based on robust research is required upon us to develop evidence for how we care for these patients. PMID:19390967

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

    MedlinePLUS

    ... Your Child All About Food Allergies Chronic Myelogenous Leukemia (CML) KidsHealth > For Parents > Chronic Myelogenous Leukemia (CML) ... Treatment Coping en espa簽ol Leucemia miel籀gena cr籀nica About Leukemia Leukemia is a type of cancer that affects ...

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

    MedlinePLUS

    ... Your Child All About Food Allergies Juvenile Myelomonocytic Leukemia (JMML) KidsHealth > For Parents > Juvenile Myelomonocytic Leukemia (JMML) ... Treatment Coping en espa簽ol Leucemia mielomonoc穩tica juvenil About Leukemia Leukemia is a type of cancer that affects ...

  4. 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

  5. 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

  6. 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

  7. [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. PMID:25016810

  8. Eosinophil viability is increased by acidic pH in a cAMP- and GPR65-dependent manner.

    PubMed

    Kottyan, Leah C; Collier, Ann R; Cao, Khanh H; Niese, Kathryn A; Hedgebeth, Megan; Radu, Caius G; Witte, Owen N; Khurana Hershey, Gurjit K; Rothenberg, Marc E; Zimmermann, Nives

    2009-09-24

    The microenvironment of the lung in asthma is acidic, yet the effect of acidity on inflammatory cells has not been well established. We now demonstrate that acidity inhibits eosinophil apoptosis and increases cellular viability in a dose-dependent manner between pH 7.5 and 6.0. Notably, acidity induced eosinophil cyclic adenosine 5'-monophosphate (cAMP) production and enhanced cellular viability in an adenylate cyclase-dependent manner. Furthermore, we identify G protein-coupled receptor 65 (GPR65) as the chief acid-sensing receptor expressed by eosinophils, as GPR65-deficient eosinophils were resistant to acid-induced eosinophil cAMP production and enhanced viability. Notably, GPR65(-/-) mice had attenuated airway eosinophilia and increased apoptosis in 2 distinct models of allergic airway disease. We conclude that eosinophil viability is increased in acidic microenvironments in a cAMP- and GPR65-dependent manner. PMID:19641187

  9. Juvenile myelomonocytic leukemia.

    PubMed

    Satwani, Prakash; Kahn, Justine; Dvorak, Christopher C

    2015-02-01

    Juvenile myelomonocytic leukemia (JMML), a rare myeloid malignancy that occurs in young children, is considered a clonal disease originating in pluripotent stem cells of the hematopoietic system. The pathogenesis of JMML involves disruption of signal transduction through the RAS pathway, with resultant selective hypersensitivity of JMML cells to granulocyte-macrophage colony-stimulating factor. Progress has been made in understanding aspects of the molecular basis of JMML. How these molecular mechanisms may lead to targeted therapeutics and improved outcomes remains to be elucidated. Allogeneic hematopoietic stem cell transplant is the only curative option for children with JMML, and it is fraught with frequent relapse and significant toxicity. PMID:25435114

  10. Vorinostat in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-04-30

    Adult Acute Erythroid Leukemia (M6); 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); Recurrent Adult Acute Myeloid Leukemia; Refractory Cytopenia With Multilineage Dysplasia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  11. Recent advances in understanding/managing eosinophilic esophagitis in adults

    PubMed Central

    Katzka, David A.

    2015-01-01

    It is an exciting time for research in eosinophilic esophagitis (EoE). As a new and increasingly prevalent disease, it is receiving considerable attention in the medical world, resulting in a flood of new insights. Clearly, a genetic predisposition seems likely with the identification of abnormalities in thymic stromal lymphopoietin (TSLP), calpain14, and eotaxin-3 genes. There are also well-defined abnormalities described in esophageal epithelial barrier function in these patients. The relationship between gastroesophageal reflux disease (GERD) and EoE remains unclear, but emerging data suggest that the concept of proton pump inhibitor responsive esophageal eosinophilia (PPIREE) may retain less importance, as this subset of patients becomes a likely subset of EoE in general. Finally, we approach the looming issue of long-term maintenance therapy. Although we lack adequate specific data on how to provide long-term pharmacologic treatment, studies clearly show that for most patients, this is a progressive disease that warrants such consideration. PMID:26339483

  12. Clinical features of Eosinophilic esophagitis in children and adults.

    PubMed

    Miehlke, Stephan

    2015-10-01

    Eosinophilic esophagitis (EoE) may affect humans at any age with a predominance for Caucasian males. The clinical manifestation of EoE varies depending on the patient's age. Infants and young children may primarily present with unspecific symptoms such as feeding problems, vomiting and abdominal pain. In adolescents and adults, dysphagia and food impactation become the predominant symptoms. EoE should also be considered in cases of refractory heartburn in both children and adults. Concomitant allergic diseases such as asthma, rhinitis and eczema, as well as peripheral eosinophilia and elevated total serum IgE values are common in pediatric and adult EoE patients. EoE seems to be primarily a food antigen-driven disease, whereas in adults, aeroallergen sensitization may dominate. Endoscopic features of EoE include mucosal edema, furrows, exudates, corrugated rings, strictures, and the so-called crepe paper sign. There appears to be a shift from an inflammatory-predominant phenotype in young childhood towards a more fibrotic phenotype in adolescents and adults. Long-term follow studies suggest that EoE is a chronic and potentially progressive disease causing recurring dysphagia in the majority of cases. The prevalence of strictures significantly increases with the duration of untreated disease, stressing the importance of early diagnosis and consequent treatment of EoE. PMID:26552773

  13. [Eosinophilic fasciitis associated with Parkinson's syndrome - a case report].

    PubMed

    Budisin, Vesna; Vrabec-Matkovi, Dragica; Milavac-Pureti, Visnja

    2013-01-01

    We present a 67 year old patient with erythema and swelling of the right arm. Suspected erysipelas and lymphedema are diagnosed at infectious department in the second month of the disease. He was treated with parenteral antibiotics (clindamycin + quinolon). After that, he was hospitalized at rheumatology department as right hand lymphedema, condition after erysipelas, cervicobrachial syndrome and ulnar epicondylitis of right elbow. Lymphatic drainage of right hand was performed, but with no effect. In the seventh month of the disease, the diagnosis of eosinophilic faciitis was established and started treatment with corticosteroids. Besides mentioned, dizziness, tremor, balance disorders, impaired hearing and pain in the cervical and lumbar spine were apeared. The therapy was introduced with levodopa and ropanirol and there is a slight improvement of neurological manifestations of extrapyramidal syndrome. After 18 months of disease the patient has a contracture of his right shoulder, induration and painful movements right forearm, pronounced tremor of the head and hands, balance disorders, neck pain and back pain, difficulty in walking. PMID:24003683

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

    ClinicalTrials.gov

    2016-02-03

    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

  15. Major basic protein from eosinophils and myeloperoxidase from neutrophils are required for protective immunity to Strongyloides stercoralis in mice.

    PubMed

    O'Connell, Amy E; Hess, Jessica A; Santiago, Gilberto A; Nolan, Thomas J; Lok, James B; Lee, James J; Abraham, David

    2011-07-01

    Eosinophils and neutrophils contribute to larval killing during the primary immune response, and neutrophils are effector cells in the secondary response to Strongyloides stercoralis in mice. The objective of this study was to determine the molecular mechanisms used by eosinophils and neutrophils to control infections with S. stercoralis. Using mice deficient in the eosinophil granule products major basic protein (MBP) and eosinophil peroxidase (EPO), it was determined that eosinophils kill the larvae through an MBP-dependent mechanism in the primary immune response if other effector cells are absent. Infecting PHIL mice, which are eosinophil deficient, with S. stercoralis resulted in development of primary and secondary immune responses that were similar to those of wild-type mice, suggesting that eosinophils are not an absolute requirement for larval killing or development of secondary immunity. Treating PHIL mice with a neutrophil-depleting antibody resulted in a significant impairment in larval killing. Na鴳e and immunized mice with neutrophils deficient in myeloperoxidase (MPO) infected with S. stercoralis had significantly decreased larval killing. It was concluded that there is redundancy in the primary immune response, with eosinophils killing the larvae through an MBP-dependent mechanism and neutrophils killing the worms through an MPO-dependent mechanism. Eosinophils are not required for the development or function of secondary immunity, but MPO from neutrophils is required for protective secondary immunity. PMID:21482685

  16. 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

  17. Workshop Report from the NIH Taskforce on the Research Needs of Eosinophil-Associated Diseases (TREAD)

    PubMed Central

    Bochner, Bruce S.; Book, Wendy; Busse, William W.; Butterfield, Joseph; Furuta, Glenn T.; Gleich, Gerald J.; Klion, Amy D.; Lee, James J.; Leiferman, Kristin M.; Minnicozzi, Michael; Moqbel, Redwan; Rothenberg, Marc E.; Schwartz, Lawrence B.; Simon, Hans-Uwe; Wechsler, Michael E.; Weller, Peter F.

    2012-01-01

    Background Eosinophils are blood cells that are often found in high numbers in the tissues of allergic conditions and helminthic parasite infections. The pathophysiological roles that eosinophils may serve in other human eosinophil-associated diseases remain obscure. Objective NIH Institutes and the Office of Disease Prevention assembled an international taskforce of clinical and basic scientists with the charge to propose and prioritize unmet research needs in eosinophil-associated diseases. Methods The taskforce used an organ system approach to dissect out the different and common themes of eosinophil cell involvement in these diseases. In early 2012, a draft document was circulated for review. The document was amended and the prioritizations were set at a NIH-organized workshop in June 2012. Results The taskforce identified significant research needs. These needs cross disease entities but some are disease-specific. There are substantial shortcomings to the various preclinical animal models, as well as significant gaps in our epidemiologic, pathophysiologic, diagnostic, prognostic and therapeutic knowledge. The taskforce recognized that recent efforts by patient advocacy groups have played instrumental roles in improving the identification and characterization of these disorders. However, communication amongst the eosinophil interested communities, e.g., governmental funding and regulatory agencies, and industry and clinician scientists need to be more comprehensive. Conclusions Significant efforts are required to address our knowledge gaps in order to improve the outcomes of eosinophil-associated diseases. NIH Institutes, other federal agencies, lay organizations and the pharmaceutical industry should consider the taskforces recommendations in their future research activities. PMID:22935587

  18. Effects of prednisone on eosinophilic bronchitis in asthma: a systematic review and meta-analysis*,**

    PubMed Central

    Sakae, Thiago Mam皾u; Maurici, Rosemeri; Trevisol, Daisson Jos; Pizzichini, Marcia Margaret Menezes; Pizzichini, Em璱io

    2014-01-01

    OBJECTIVE: To evaluate the effect size of oral corticosteroid treatment on eosinophilic bronchitis in asthma, through systematic review and meta-analysis. METHODS: We systematically reviewed articles in the Medline, Cochrane Controlled Trials Register, EMBASE, and LILACS databases. We selected studies meeting the following criteria: comparing at least two groups or time points (prednisone vs. control, prednisone vs. another drug, or pre- vs. post-treatment with prednisone); and evaluating parameters before and after prednisone use, including values for sputum eosinophils, sputum eosinophil cationic protein (ECP), and sputum IL-5-with or without values for post-bronchodilator FEV1-with corresponding 95% CIs or with sufficient data for calculation. The independent variables were the use, dose, and duration of prednisone treatment. The outcomes evaluated were sputum eosinophils, IL-5, and ECP, as well as post-bronchodilator FEV1. RESULTS: The pooled analysis of the pre- vs. post-treatment data revealed a significant mean reduction in sputum eosinophils (?8.18%; 95% CI: 7.69-8.67; p < 0.001), sputum IL-5 (?83.64 pg/mL; 95% CI: 52.45-114.83; p < 0.001), and sputum ECP (?267.60 痢/L; 95% CI: 244.57-290.63; p < 0.0001), as well as a significant mean increase in post-bronchodilator FEV1 (?8.09%; 95% CI: 5.35-10.83; p < 0.001). CONCLUSIONS: In patients with moderate-to-severe eosinophilic bronchitis, treatment with prednisone caused a significant reduction in sputum eosinophil counts, as well as in the sputum levels of IL-5 and ECP. This reduction in the inflammatory response was accompanied by a significant increase in post-bronchodilator FEV1. PMID:25410844

  19. Salbutamol delays human eosinophil apoptosis via a cAMP-dependent mechanism.

    PubMed

    Kankaanranta, Hannu; Parkkonen, Jouni; Ilmarinen-Salo, Pinja; Giembycz, Mark A; Moilanen, Eeva

    2011-08-01

    Eosinophils play a major role in asthma. One described mechanism leading to the impaired clearance of these cells from the lung is the delay in their programmed cell death (apoptosis). ?(2)-Adrenoceptor agonists have been shown to prolong survival and delay apoptosis of eosinophils. The aim of the present study was to evaluate the mechanisms, especially the role of cAMP pathway, in the prolongation of human eosinophil survival by a selective ?(2)-agonist salbutamol. Isolated human peripheral blood eosinophils were cultured in the absence or presence of a ?(2)-agonist salbutamol and the indicated antagonists/inhibitors under sterile conditions. Apoptosis was measured by using the relative DNA fragmentation assay and Annexin-V binding. Salbutamol prolonged survival of human eosinophils and it was inhibited by a ?-receptor antagonist propranolol and mimicked by cell-permeant cAMP analogues dibutyryl- and 8-bromo-cAMP. Pharmacological inhibitors of adenylyl cyclase (SQ-22,536) and protein kinase A (Rp-8-CPT-cAMPS) antagonized the effects of salbutamol. The survival-prolonging action of salbutamol was potentiated by a phosphodiesterase inhibitor rolipram (EC(50) for the salbutamol effect was 13.6 4.0 and 8.1 3.1 nM in the absence and presence of rolipram, respectively; p=0.0142, n=10). In contrast, inhibition of Ca(2+)-activated K(+)-channels by apamin, charybdotoxin, iberiotoxin or paxilline did not affect the ability of salbutamol to prolong eosinophil survival. Taken together, the present results suggest that salbutamol at clinically relevant concentrations decreases apoptosis in human eosinophils by activating the cannonical ?(2)-receptor-adenylyl cyclase-cAMP-protein kinase A pathway. PMID:21396479

  20. Management of prolymphocytic leukemia.

    PubMed

    Dearden, Claire

    2015-12-01

    B-cell (B-PLL) and T-cell (T-PLL) prolymphocytic leukemias are rare, poor-prognosis lymphoid neoplasms with similar presentation characterized by symptomatic splenomegaly and lymphocytosis. They can be distinguished from each other and from other T- and B-cell leukemias by careful evaluation of morphology, immunophenotyping, and molecular genetics. The clinical behavior is typically aggressive, although a subset of patients may have an indolent phase of variable length. First-line therapy for T-PLL is with intravenous alemtuzumab and for B-PLL is with combination purine analog-based chemo-immunotherapy. New B-cell receptor inhibitors, such as ibrutinib and idelalisib, may have a role in the management of B-PLL, especially for the patients harboring abnormalities of TP53. Allogenic stem cell transplantation should still be considered for eligible patients and may be the only current therapy capable of delivering a cure. In the past few years, many of the molecular mechanisms underlying disease pathogenesis and progression have been revealed and are likely to lead to the development of novel targeted approaches. PMID:26637744

  1. Phosphodiesterase 4 inhibitors delay human eosinophil and neutrophil apoptosis in the absence and presence of salbutamol.

    PubMed

    Parkkonen, Jouni; Hasala, Hannele; Moilanen, Eeva; Giembycz, Mark A; Kankaanranta, Hannu

    2008-01-01

    In asthma and chronic obstructive pulmonary disease (COPD), the number of eosinophils and neutrophils in the lung is increased. One described mechanism leading to the impaired clearance of these cells from the lung is the delay in their programmed cell death (apoptosis). Selective inhibitors of phosphodiesterases (PDEs) are under development for the treatment of lung diseases because of their anti-inflammatory and bronchodilator activity. The aim of the present study was to establish whether inhibitors of PDE3, PDE4 and PDE5 modulate human eosinophil or neutrophil apoptosis or beta 2-adrenoceptor agonist- or cytokine-afforded survival. We also evaluated whether a PDE4 inhibitor could modulate the effect of a corticosteroid on eosinophil and neutrophil apoptosis. Apoptosis was measured by using the relative DNA fragmentation assay and Annexin-V binding. Inhibitors of PDE4 (rolipram; 0.1-10 microM) and PDE3 (cilostazol; 0.1-10 microM) delayed spontaneous eosinophil apoptosis maximally by 25% and 15%, respectively. A combination of a PDE4 or PDE3 inhibitor (10 microM) with salbutamol (100 nM) further delayed eosinophil apoptosis maximally by 42-49%. In neutrophils, rolipram (10 microM) also decreased apoptosis with a maximal inhibition of 13%. The combination of rolipram (10 microM) and salbutamol (100 nM) produced a 27% inhibition of neutrophil apoptosis. Inhibitor of cGMP-specific PDE5 (zaprinast; 0.1-10 microM) did not affect eosinophil apoptosis and only slightly increased spontaneous neutrophil apoptosis. The effect of budesonide on apoptosis was not significantly modulated by a PDE4 inhibitor in eosinophils or neutrophils. The present results show that selective inhibitors of cAMP-hydrolyzing PDEs (PDE3 and PDE4) delay eosinophil apoptosis and, thus, increase their survival in vitro. Furthermore, beta 2-adrenoceptor agonists enhance the anti-apoptotic effects of PDE3 and PDE4 inhibitors, suggesting that such drug combinations may prolong eosinophil and neutrophil longevity in the lung. PMID:18282775

  2. 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

  3. Clinical Manifestations and Treatment Outcomes of Eosinophilic Gastroenteritis in Children

    PubMed Central

    Choi, Jong Sub; Choi, Shin Jie; Lee, Kyung Jae; Kim, Ahlee; Yoo, Jung Kyung; Yang, Hye Ran; Moon, Jin Soo; Chang, Ju Young; Kang, Gyeong Hoon

    2015-01-01

    Purpose The aim of the present study was to investigate the clinical features and outcome of eosinophilic gastroenteritis (EGE) in children. Methods Our study enrolled 24 children who were diagnosed with EGE from 1993 to 2014 at the Department of Pediatrics, Seoul National University Children's Hospital. The patients' clinical manifestations, treatments, and outcomes were reviewed from the medical records. Results The mean age at diagnosis was 5.3 years. Most patients had gastrointestinal symptoms including diarrhea (54.2%) and abdominal pain (45.8%). Peripheral eosinophilia was present in 91.7% of the patients. Thirteen patients (54.2%) showed anemia, and 15 patients (62.5%) had hypoalbuminemia. EGE was classified as mucosal, subserosal, or muscular in 75.0%, 20.8%, and 4.2% of cases, respectively. Three patients showed gastroduodenal ulcers upon endoscopic analysis. A history of allergy was reported in 13 patients, including atopic dermatitis, allergic rhinitis, and asthma. Five patients (20.8%) improved with food restrictions. Among the 19 patients treated with steroids, 11 (57.9%) discontinued steroid treatment without subsequent relapse, 4 (21.1%) relapsed after ceasing steroid treatment, and 4 (21.1%) showed no response to steroids. Two patients who were resistant to steroids underwent therapeutic surgery. The presence of gastroduodenal ulcers was significantly associated with relapse and steroid resistance. Conclusion A high suspicion of EGE is warranted when children have nonspecific gastrointestinal symptoms and peripheral eosinophilia. Most patients improved with food restrictions or steroid treatment, although one-third of patients showed a relapse or steroid resistance. PMID:26770900

  4. Eosinophilic pustular folliculitis: a comprehensive review of treatment options.

    PubMed

    Ellis, Elliot; Scheinfeld, Noah

    2004-01-01

    Eosinophilic pustular folliculitis (EPF), also known as Ofuji disease, is a disease that manifests with follicular papules or pustules. Its variants include a classic type that occurs most commonly in Japan, an HIV-associated type, an infantile type, a type that occurs on the palms and soles, a rare medication-associated variant, and a rare neoplasia-associated variant.A wide range of medications has been used to treat EPF. Topical corticosteroids are the first-line treatment option for EPF. Topical tacrolimus seems to be useful initial therapy as well. Oral indometacin (50-75 mg/day) is an effective treatment of classic EPF although it can induce peptic ulcers. For treatment of HIV-associated EPF when topical corticosteroids and indometacin do not work, various other treatments should be considered. These treatment options include cetirizine 20-40 mg/day, metronidazole 250 mg three times a day, itraconazole starting at a dosage of 200 mg/day and increasing to 300-400 mg/day, and topical permethrin. If these treatments do not work phototherapy with UVB is the 'gold standard' of treatment and is often curative. Treatments with less certain risk-benefit ratios but with some efficacy include PUVA (psoralen + UVA) photochemotherapy, oral corticosteroids, synthetic retinoids (i.e. isotretinoin 1 mg/kg/day), and acitretin (0.5 mg/kg/day), oral cyclosporine (ciclosporine) 5 mg/kg/day, interferon (IFN)-alpha-2b, and IFNgamma. Minocycline 100mg twice daily and dapsone 50-100mg twice daily have been used with some effect. The use of highly active antiretroviral therapy for HIV has resulted in the amelioration of EPF as CD4 cell counts rise above 250/mm(3). The diversity of clinical presentations and affected populations make it seem that EPF is a reaction pattern as much as a disease and that therapy should be tailored to the variant of EPF and the underlying etiology. PMID:15186198

  5. Eosinophilic pneumonias in children: A review of the epidemiology, diagnosis, and treatment.

    PubMed

    Giovannini-Chami, Lisa; Blanc, Sibylle; Hadchouel, Alice; Baruchel, Andr矇; Boukari, Rachida; Dubus, Jean-Christophe; Fayon, Michael; Le Bourgeois, Muriel; Nathan, Nadia; Albertini, Marc; Cl矇ment, Annick; de Blic, Jacques

    2016-02-01

    Pediatric eosinophilic pneumonias (EPs) are characterized by a significant infiltration of the alveolar spaces and lung interstitium by eosinophils, with conservation of the lung structure. In developed countries, EPs constitute exceptional entities in pediatric care. Clinical symptoms may be transient (L繹ffler syndrome), acute (<1 month and mostly <7 days), or chronic (>1 month). Diagnosis relies on demonstration of alveolar eosinophilia on bronchoalveolar lavage, whether or not associated with blood eosinophilia. EPs are a heterogeneous group of disorders divided into: (i) secondary forms (seen mainly in parasitic infections, allergic bronchopulmonary aspergillosis, and drug reactions); and (ii) primary forms (eosinophilic granulomatosis with polyangiitis, hypereosinophilic syndrome, idiopathic chronic eosinophilic pneumonia, and idiopathic acute eosinophilic pneumonia). Despite their rarity, the etiological approach to EP must be well-defined as some causes can be rapidly life-threatening without initiation of the proper treatment. This approach (i) eliminates secondary forms, with comprehensive history taking and minimal biological assessment, (ii) is oriented in primary forms by the acute or chronic setting, and the existence of extrapulmonary symptoms. Treatment of primary forms has traditionally relied on corticosteroids, usually with a dramatic response. Specific treatments or the adjunction of corticosteroid-sparing treatment or immunosuppressors are currently being evaluated in order to improve the prognosis and the side effects associated with corticosteroid treatment in a pediatric setting. Pediatr Pulmonol. 2016;51:203-216. 穢 2015 Wiley Periodicals, Inc. PMID:26716396

  6. Eosinophilic Angiocentric Fibrosis of Sinonasal Region: A Rare & Under Reported Entity

    PubMed Central

    Selhi, Pavneet Kaur; Munjal, Manish; Sood, Neena

    2015-01-01

    Eosinophilic angiocentric fibrosis is a rare pathology of the sinonasal tract and the upper respiratory system characterised by fibrosis with poorly understood pathogenesis. A 47-year-old male presented with a swelling over the dorsum of the nose. The possibility of fungal granuloma was being suggested on Magnetic Resonance Imaging (MRI). Histopathology showed thick collagen bundles whorling around vessels giving an onion skin appearance with focal area of vasculitis. An inflammatory reaction rich in eosinophils along with a fibrotic stroma was seen which was highly characteristic of eosinophilic angiocentric fibrosis. Clinically & microscopically it mimics Granuloma faciale, Wegeners Granulomatosis, Churg-Strauss Syndrome, Kimuras disease and few other granulomatous conditions thus making diagnosis difficult. A probable allergic origin is being suggested because of the typical eosinophil-rich inflammatory reaction. Finally the diagnosis of Eosinophilic Angiocentric Fibrosis was given. It is a diagnosis of exclusion having characteristic histomorphological findings thus biopsy is always required to distinguish it from other lesions whose treatment differs. PMID:26674883

  7. Recalcitrant eosinophilic pustular folliculitis of Ofuji with palmoplantar pustulosis: dramatic response to narrowband UVB phototherapy.

    PubMed

    Lim, Hua Liang; Chong, Wei-Sheng

    2012-08-01

    Eosinophilic pustular folliculitis of Ofuji is a recalcitrant disease typified by non-infective eosinophilic spongiosis involving the infundibular region of the hair follicle. We present a case of a 49-year-old Chinese man with known palmoplantar pustulosis and acrodermatitis continua of Hallopeau which was promptly resolved with methotrexate therapy. He returned with an erythematous papulopustular eruption with coalescence to annular plaques, occurring over the face, chest and back with active palmoplantar pustulation. Histology from skin biopsy of the palmar lesion was in keeping with palmoplantar psoriasis, while biopsy of the facial and truncal lesions revealed florid perifollicular eosinophilic congregation diagnostic of eosinophilic pustular folliculitis of Ofuji. Indomethacin was initiated with partial improvement of lesions with cyclical flares. A trial of narrowband ultraviolet-B phototherapy at a frequency of thrice weekly achieved sustained clearance of both eosinophilic pustular folliculitis and palmoplantar lesions. Indomethacin was tailed down and eventually discontinued with maintenance of narrowband ultraviolet-B therapy; this achieved successful control of the disease. PMID:23017177

  8. Allergic pulmonary inflammation in mice is dependent on eosinophil-induced recruitment of effector T cells

    PubMed Central

    Jacobsen, Elizabeth A.; Ochkur, Sergei I.; Pero, Ralph S.; Taranova, Anna G.; Protheroe, Cheryl A.; Colbert, Dana C.; Lee, Nancy A.; Lee, James J.

    2008-01-01

    The current paradigm surrounding allergen-mediated T helper type 2 (Th2) immune responses in the lung suggests an almost hegemonic role for T cells. Our studies propose an alternative hypothesis implicating eosinophils in the regulation of pulmonary T cell responses. In particular, ovalbumin (OVA)-sensitized/challenged mice devoid of eosinophils (the transgenic line PHIL) have reduced airway levels of Th2 cytokines relative to the OVA-treated wild type that correlated with a reduced ability to recruit effector T cells to the lung. Adoptive transfer of Th2-polarized OVA-specific transgenic T cells (OT-II) alone into OVA-challenged PHIL recipient mice failed to restore Th2 cytokines, airway histopathologies, and, most importantly, the recruitment of pulmonary effector T cells. In contrast, the combined transfer of OT-II cells and eosinophils into PHIL mice resulted in the accumulation of effector T cells and a concomitant increase in both airway Th2 immune responses and histopathologies. Moreover, we show that eosinophils elicit the expression of the Th2 chemokines thymus- and activation-regulated chemokine/CCL17 and macrophage-derived chemokine/CCL22 in the lung after allergen challenge, and blockade of these chemokines inhibited the recruitment of effector T cells. In summary, the data suggest that pulmonary eosinophils are required for the localized recruitment of effector T cells. PMID:18316417

  9. Human Eosinophil Leukocytes Express Protein Disulfide Isomerase in Secretory Granules and Vesicles

    PubMed Central

    Dias, Felipe F.; Amaral, K嫢ia B.; Carmo, L癉ia A. S.; Shamri, Revital; Dvorak, Ann M.; Weller, Peter F.

    2014-01-01

    Protein disulfide isomerase (PDI) has fundamental roles in the oxidative folding of proteins in the endoplasmic reticulum (ER) of eukaryotic cells. The study of this molecule has been attracting considerable attention due to its association with other cell functions and human diseases. In leukocytes, such as neutrophils, PDI is involved with cell adhesion, signaling and inflammation. However, the expression of PDI in other leukocytes, such as eosinophils, important cells in inflammatory, allergic and immunomodulatory responses, remains to be defined. Here we used different approaches to investigate PDI expression within human eosinophils. Western blotting and flow cytometry demonstrated high PDI expression in both unstimulated and CCL11/eotaxin-1-stimulated eosinophils, with similar levels in both conditions. By using an immunogold electron microscopy technique that combines better epitope preservation and secondary Fab-fragments of antibodies linked to 1.4-nm gold particles for optimal access to microdomains, we identified different intracellular sites for PDI. In addition to predictable strong PDI labeling at the nuclear envelope, other unanticipated sites, such as secretory granules, lipid bodies and vesicles, including large transport vesicles (eosinophil sombrero vesicles), were also labeled. Thus, we provide the first identification of PDI in human eosinophils, suggesting that this molecule may have additional/specific functions in these leukocytes. PMID:24670795

  10. Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses

    PubMed Central

    Blanchard, C; Mingler, MK; McBride, M; Putnam, PE; Collins, MH; Chang, G; Stringer, K; Abonia, JP; Molkentin, JD; Rothenberg, ME

    2009-01-01

    Periostin is an extracellular matrix protein that has been primarily studied in the context of the heart, where it has been shown to promote cardiac repair and remodeling. In this study, we focused on the role of periostin in an allergic eosinophilic inflammatory disease (eosinophilic esophagitis (EE)) known to involve extensive tissue remodeling. Periostin was indeed markedly overexpressed (35-fold) in the esophagus of EE patients, particularly in the papillae, compared with control individuals. Periostin expression was downstream from transforming growth factor-? and interleukin-13, as these cytokines were elevated in EE esophageal samples and markedly induced periostin production by primary esophageal fibroblasts (107- and 295-fold, respectively, at 10 ng ml?1). A functional role for periostin in eliciting esophageal eosinophilia was demonstrated, as periostin-null mice had a specific defect in allergen-induced eosinophil recruitment to the lungs and esophagus (66 and 72% decrease, respectively). Mechanistic analyses revealed that periostin increased (5.8-fold) eosinophil adhesion to fibronectin. As such, these findings extend the involvement of periostin to esophagitis and uncover a novel role for periostin in directly regulating leukocyte (eosinophil) accumulation in T helper type 2-associated mucosal inflammation in both mice and humans. PMID:19079190

  11. Periostin facilitates eosinophil tissue infiltration in allergic lung and esophageal responses.

    PubMed

    Blanchard, C; Mingler, M K; McBride, M; Putnam, P E; Collins, M H; Chang, G; Stringer, K; Abonia, J P; Molkentin, J D; Rothenberg, M E

    2008-07-01

    Periostin is an extracellular matrix protein that has been primarily studied in the context of the heart, where it has been shown to promote cardiac repair and remodeling. In this study, we focused on the role of periostin in an allergic eosinophilic inflammatory disease (eosinophilic esophagitis (EE)) known to involve extensive tissue remodeling. Periostin was indeed markedly overexpressed (35-fold) in the esophagus of EE patients, particularly in the papillae, compared with control individuals. Periostin expression was downstream from transforming growth factor-beta and interleukin-13, as these cytokines were elevated in EE esophageal samples and markedly induced periostin production by primary esophageal fibroblasts (107- and 295-fold, respectively, at 10 ng ml(-1)). A functional role for periostin in eliciting esophageal eosinophilia was demonstrated, as periostin-null mice had a specific defect in allergen-induced eosinophil recruitment to the lungs and esophagus (66 and 72% decrease, respectively). Mechanistic analyses revealed that periostin increased (5.8-fold) eosinophil adhesion to fibronectin. As such, these findings extend the involvement of periostin to esophagitis and uncover a novel role for periostin in directly regulating leukocyte (eosinophil) accumulation in T helper type 2-associated mucosal inflammation in both mice and humans. PMID:19079190

  12. High Fat Diet Causes Depletion of Intestinal Eosinophils Associated with Intestinal Permeability

    PubMed Central

    Johnson, Andrew M. F.; Costanzo, Anne; Gareau, Melanie G.; Armando, Aaron M.; Quehenberger, Oswald; Jameson, Julie M.; Olefsky, Jerrold M.

    2015-01-01

    The development of intestinal permeability and the penetration of microbial products are key factors associated with the onset of metabolic disease. However, the mechanisms underlying this remain unclear. Here we show that, unlike liver or adipose tissue, high fat diet (HFD)/obesity in mice does not cause monocyte/macrophage infiltration into the intestine or pro-inflammatory changes in gene expression. Rather HFD causes depletion of intestinal eosinophils associated with the onset of intestinal permeability. Intestinal eosinophil numbers were restored by returning HFD fed mice to normal chow and were unchanged in leptin-deficient (Ob/Ob) mice, indicating that eosinophil depletion is caused specifically by a high fat diet and not obesity per se. Analysis of different aspects of intestinal permeability in HFD fed and Ob/Ob mice shows an association between eosinophil depletion and ileal paracelullar permeability, as well as leakage of albumin into the feces, but not overall permeability to FITC dextran. These findings provide the first evidence that a high fat diet causes intestinal eosinophil depletion, rather than inflammation, which may contribute to defective barrier integrity and the onset of metabolic disease. PMID:25837594

  13. [Two cases of eosinophilic gastroenteritis whose causative allergens are usefully diagnosed by patch test].

    PubMed

    Adachi, Atsuko

    2010-05-01

    Case 1: 67-years-old woman with pollinosis noticed oppressive feeling of chest and back, and heart burn after accidental ingestion of her dental filling and dental treatment. Oral famotidine did not improve her symptom. Her peripheral blood eosinophils increased to 38.0%. As for the specific IgE, only cedar and cypress were positive. Case 2: a 42-years-old-woman with pollinosis and asthma repeated urticaria, heart burn, diarrhea and peripheral eosinophilia (25%). At her first visit to our department, her blood eosinophil increased to 52.9%, her serum IgG markedly increased in polyclonal pattern and overt all subclasses. The specific IgE was positive only for cypress. Because they revealed a remarkable infiltrates of eosinophils in the mucosa of alimentary tract, we diagnosed the 2 patient as eosinophilic gastroenteritis. In case 1, based on the history and patch-test-positive finding of formalin and 2-hydroxyethyl methacrylate, we diagnosed the two may be causative allergens. In case 2, based on the patch-test-positive finding of garlic and sesame and improvement after removal of the two allergens, we diagnosed the two may be causative allergens. Although causative allergens of eosinophilic gastroenteritis are almost unknown, some cases are reported to be determined the allergens of foods and drugs. In our cases, patch test was useful to identify the allergens. PMID:20502103

  14. Eosinophilic Angiocentric Fibrosis of Sinonasal Region: A Rare & Under Reported Entity.

    PubMed

    Singh, Aminder; Selhi, Pavneet Kaur; Munjal, Manish; Sood, Neena

    2015-11-01

    Eosinophilic angiocentric fibrosis is a rare pathology of the sinonasal tract and the upper respiratory system characterised by fibrosis with poorly understood pathogenesis. A 47-year-old male presented with a swelling over the dorsum of the nose. The possibility of fungal granuloma was being suggested on Magnetic Resonance Imaging (MRI). Histopathology showed thick collagen bundles whorling around vessels giving an onion skin appearance with focal area of vasculitis. An inflammatory reaction rich in eosinophils along with a fibrotic stroma was seen which was highly characteristic of eosinophilic angiocentric fibrosis. Clinically & microscopically it mimics Granuloma faciale, Wegener's Granulomatosis, Churg-Strauss Syndrome, Kimura's disease and few other granulomatous conditions thus making diagnosis difficult. A probable allergic origin is being suggested because of the typical eosinophil-rich inflammatory reaction. Finally the diagnosis of Eosinophilic Angiocentric Fibrosis was given. It is a diagnosis of exclusion having characteristic histomorphological findings thus biopsy is always required to distinguish it from other lesions whose treatment differs. PMID:26674883

  15. Expression of eosinophils be beneficial to early clinical diagnosis of brucellosis

    PubMed Central

    Jiao, Peng-Fei; Chu, Wei-Li; Ren, Gao-Fei; Hou, Jun-Na; Li, Ya-Meng; Xing, Li-Hua

    2015-01-01

    Objective: Investigate the expression and significance of eosinophils in brucellosis. Methods: Retrospective analysis of clinical data for 151 brucellosis patients (BR group), complete blood count and blood bacterial culture etc.; in addition, 150 general bacterial infection patients (BI group) and 135 persons in healthy physical condition upon testing (NC group) are selected respectively as the control groups to comparatively study expression of white blood cells and eosinophils for brucellosis patients. Adopt t test to compare measurement data. Results: In comparison with BI group, WBC, NE, EO, MO, NE% and EO% in BR group are reduced but LY, LY% and MO% are increased and such difference shows statistical significance (P<0.01). In comparison with NC group, difference of WBC and NE in BR group shows no statistical significance (P>0.05). NE%, EO and EO% are reduced but MO, LY% and MO% are increased and such difference shows statistical significance (P<0.01). LY is increased and the difference shows statistical significance (P<0.05). White blood cell count is normal or is reduced among most of Brucellosis patients, accounting for 90.73% (137/151); the patients whose eosinophils are reduced account for 75.50% (114/151) and those whose eosinophils disappear are about 18.54% (28/151). Conclusion: There is an incidence rate of eosinophils decrease or disappearance in Brucellosis and it shows the indication significance in the diagnosis of early disease. PMID:26770598

  16. Interleukin-5 Priming of Human Eosinophils Alters Siglec-8Mediated Apoptosis Pathways

    PubMed Central

    Nutku-Bilir, Esra; Hudson, Sherry A.; Bochner, Bruce S.

    2008-01-01

    Previously, we have identified the sequential activation of reactive oxygen species (ROS), mitochondria, and caspase-3, -8, and -9, in Siglec-8mediated eosinophil apoptosis. Cytokine priming, which normally prolongs eosinophil survival, paradoxically potentiated this proapoptotic effect. The mechanisms of Siglec-8mediated apoptosis after priming were therefore explored. Using IL-5 as the priming stimulus, the rate of Siglec-8induced eosinophil apoptosis was found to be enhanced compared with unprimed cells, and mechanisms differed after IL-5 priming in that neither a pan-caspase inhibitor, nor a specific caspase-3 inhibitor, could override apoptosis. IL-5 priming also accelerated Siglec-8mediated dissipation of mitochondrial membrane potential. Finally, both the mitochondrial electron transport inhibitor rotenone, and the ROS inhibitors diphenyleneiodonium and antimycin, completely inhibited Siglec-8mediated apoptosis, even after IL-5 priming. These data demonstrate that IL-5 priming enhances Siglec-8mediated mitochondrial and ROS-dependent eosinophil apoptosis and eliminates caspase dependence. The potential clinical implication of these findings is that cytokine priming, as often occurs in vivo in asthma and other hypereosinophilic disorders, may render eosinophils from such patients especially susceptible to the proapoptotic effects of a Siglec-8engaging therapeutic agent. PMID:17690326

  17. Decitabine in Treating Patients With Previously Untreated Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-02-25

    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

  18. Gemtuzumab Ozogamicin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-09-23

    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

  19. PXD101 in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-10-08

    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); Recurrent Adult Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  20. Decitabine and Bortezomib in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-11-06

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

  1. 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

  2. Human eosinophil adhesion and degranulation stimulated with eotaxin and RANTES in vitro: Lack of interaction with nitric oxide

    PubMed Central

    Lintomen, Let獳ia; Franchi, Gilberto; Nowill, Alexandre; Condino-Neto, Antonio; de Nucci, Gilberto; Zanesco, Angelina; Antunes, Edson

    2008-01-01

    Background Airway eosinophilia is considered a central event in the pathogenesis of asthma. The toxic components of eosinophils are thought to be important in inducing bronchial mucosal injury and dysfunction. Previous studies have suggested an interaction between nitric oxide (NO) and chemokines in modulating eosinophil functions, but this is still conflicting. In the present study, we have carried out functional assays (adhesion and degranulation) and flow cytometry analysis of adhesion molecules (VLA-4 and Mac-1 expression) to evaluate the interactions between NO and CC-chemokines (eotaxin and RANTES) in human eosinophils. Methods Eosinophils were purified using a percoll gradient followed by immunomagnetic cell separator. Cell adhesion and degranulation were evaluated by measuring eosinophil peroxidase (EPO) activity, whereas expression of Mac-1 and VLA-4 was detected using flow cytometry. Results At 4 h incubation, both eotaxin (100 ng/ml) and RANTES (1000 ng/ml) increased by 133% and 131% eosinophil adhesion, respectively. L-NAME alone (but not D-NAME) also increased the eosinophil adhesion, but the co-incubation of L-NAME with eotaxin or RANTES did not further affect the increased adhesion seen with chemokines alone. In addition, L-NAME alone (but not D-NAME) caused a significant cell degranulation, but it did not affect the CC-chemokine-induced cell degranulation. Incubation of eosinophils with eotaxin or RANTES, in absence or presence of L-NAME, did not affect the expression of VLA-4 and Mac-1 on eosinophil surface. Eotaxin and RANTES (100 ng/ml each) also failed to elevate the cyclic GMP levels above baseline in human eosinophils. Conclusion Eotaxin and RANTES increase the eosinophil adhesion to fibronectin-coated plates and promote cell degranulation by NO-independent mechanisms. The failure of CC-chemokines to affect VLA-4 and Mac-1 expression suggests that changes in integrin function (avidity or affinity) are rather involved in the enhanced adhesion. PMID:18700028

  3. Sialyltransferase ST3Gal-III regulates Siglec-F ligand formation and eosinophilic lung inflammation in mice

    PubMed Central

    Suzukawa, Maho; Miller, Marina; Rosenthal, Peter; Cho, Jae Youn; Doherty, Taylor; Varki, Ajit; Broide, David

    2013-01-01

    Siglec-F is highly expressed on mouse eosinophils and plays an important role in regulating levels of eosinophilic lung inflammation. In this study we investigated the mechanism of constitutive and inducible Siglec-F ligand expression by lung airway epithelial cells and inflammatory cells in WT and genetically altered mice (ST3Gal-III heterozygotes; Fuc-TIV/VII double null; STAT6 null). Flow cytometry demonstrated that Siglec-F ligands are constitutively expressed in vitro and in vivo in selected lung cell types (epithelial cells, eosinophils, macrophages, mast cells, but not CD4, CD8, or B cells) and induced in response to divergent stimuli including innate stimuli (TLR ligands, Alternaria), Th2 cytokines (IL-4, IL-13), and adaptive immune stimuli (OVA allergen). Furthermore studies of deficient mice demonstrated the greater importance of the sialyltransferase ST3Gal-III compared to fucosyltransferases Fuc-TIV/VII in the synthesis of the constitutive and inducible Siglec-F ligands by lung epithelial and non-epithelial cells. In keeping with this, ST3Gal-III heterozygote mice (deficient in expression of Siglec-F ligands) also had significantly enhanced OVA-induced eosinophilic airway inflammation associated with reduced eosinophil apoptosis. Reduced eosinophil apoptosis in the lung of ST3Gal-III deficient mice is likely mediated by reduced epithelial expression of Siglec-F ligands as WT eosinophils (which highly express Siglec-F) cultured with ST3Gal-III deficient epithelial cells (which do not express Siglec-F ligand) showed reduced eosinophil apoptosis compared to WT eosinophils cultured with WT epithelial cells. Overall, these studies demonstrate that ST3Gal-III plays an important role in Siglec-F ligand formation and eosinophil apoptosis with resultant effects on eosinophilic inflammation in the lung. PMID:23677475

  4. Genetic predispositions to childhood leukemia

    PubMed Central

    Stieglitz, Elliot

    2013-01-01

    While the majority of leukemia cases occur in the absence of any known predisposing factor, there are germline mutations that significantly increase the risk of developing hematopoietic malignancies in childhood. In this review article, we describe a number of these mutations and their clinical features. These predispositions can be broadly classified as those leading to bone marrow failure, those involving tumor suppressor genes, DNA repair defects, immunodeficiencies or other congenital syndromes associated with transient myeloid disorders. While leukemia can develop as a secondary event in the aforementioned syndromes, there are also several syndromes that specifically lead to the development of leukemia as their primary phenotype. Many of the genes discussed in this review can also be somatically mutated in other cancers, highlighting the importance of understanding shared alterations and mechanisms underpinning syndromic and sporadic leukemia. PMID:23926459

  5. Management of chronic lymphocytic leukemia

    PubMed Central

    Ghia, Paolo; Hallek, Michael

    2014-01-01

    In the last decade, the management of chronic lymphocytic leukemia has undergone profound changes that have been driven by an improved understanding of the biology of the disease and the approval of several new drugs. Moreover, many novel drugs are currently under evaluation for rapid approval or have been approved by regulatory agencies, further broadening the available therapeutic armamentarium for patients with chronic lymphocytic leukemia. The use of novel biological and genetic parameters combined with a careful clinical evaluation allows us to dissect some of the heterogeneity of the disease and to distinguish patients with a very mild onset and course, who often will not need any treatment, from those with an intermediate prognosis and a third group with a very aggressive course (high-risk leukemia). On this background, it becomes increasingly challenging to select the right treatment strategy. In this paper, we describe our own approach to the management of different patients with chronic lymphocytic leukemia. PMID:24881042

  6. What Is Acute Myeloid Leukemia?

    MedlinePLUS

    ... will talk about acute myeloid leukemia (AML). Normal bone marrow and blood cells To understand the different types ... into the bloodstream, and spread to other organs. Bone marrow Bone marrow is the soft, spongy, inner part ...

  7. How Is Childhood Leukemia Classified?

    MedlinePLUS

    ... also called Burkitt leukemia ). This type is rare, accounting for only about 2% to 3% of childhood ... cutoffs to define the phases, but a common system (proposed by the World Health Organization) is described ... Prevention & Detection Signs & Symptoms of ...

  8. Leukemia diagnosis: today and tomorrow.

    PubMed

    B幯, Marie C; Grimwade, David; Haferlach, Claudia; Haferlach, Torsten; Zini, Gina

    2015-10-01

    The European LeukemiaNet (ELN) is composed of several work packages, four of them being directly involved in the various aspects of diagnosis. On the occasion of the annual ELN meeting of 2015 in Mannheim, these four work packages collectively examined the current situation and future prospects of cytomorphology, flow cytometry, cytogenetics, next-generation sequencing, and minimal residual disease detection in the context of leukemia diagnosis and follow-up. This document summarizes the outcome of this compendium. PMID:26110830

  9. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2015-09-30

    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

  10. [Chronic myeloid leukemia].

    PubMed

    Usui, Noriko

    2014-06-01

    More than 10 years have passed since imatinib as a first developed BCR-ABL tyrosine kinase inhibitor (TKI) introduced in treatment of patients with chronic myeloid leukemia (CML). In globally, there are tremendous numbers of patients on imatinib therapy. Based upon randomized trials comparing second generation TKIs such as dasatinib and nilotinib versus imatinib, both TKIs produce faster and deeper response than imatinib and they can be selected as first-line therapy for newly diagnosed chronic phase of CML (CP-CML) as imatinib. Bosutinib is a potent for imatinib resistant/intolerant CP-CML and can be used as second or third-line therapy. Ponatinib is the only clinically available TKI that has activity against the T315 mutation that is resistant to all other TKIs. Currently, a choice among these potent TKIs should take into consideration the drug side effect profiles and the patient's comorbidities. PMID:25016806

  11. [Plasma cell leukemia].

    PubMed

    Ravinet, Aur幨ie; Bay, Jacques Olivier; Tournilhac, Olivier

    2014-11-01

    Plasma cell leukemia (PCL) is a rare disorder which develops spontaneously (primary PCL) or evolves in patients with multiple myeloma (secondary PCL). It is defined by the presence of 2 10(9)/L peripheral blood plasma cells or plasmacytosis accounting for more than 20 % of the differential white cell count. PCL presents more often extramedullary involvement, anemia, thrombocytopenia, hypercalcemia, as well as impaired renal function. Cytogenetic abnormalities and mutations observed in PCL lead to escape from immune surveillance and independence from the bone marrow microenvironment with changes in expression of adhesion molecules or chemokines receptors. The outcome of PCL has improved with combination approaches with novel agents (including bortezomib and immunomodulatory drugs, such as lenalidomide) and with autologous stem cell transplantation. Allogeneic hematopoietic stem cell transplantation is currently available for young patients. This article is an overview of this rare and severe disease and the different therapeutics options that are recommended. PMID:25418598

  12. Immunotherapy in acute myeloid leukemia.

    PubMed

    Arpinati, Mario; Curti, Antonio

    2014-01-01

    Treatment of acute myeloid leukemia (AML) with current chemotherapy regimens is still disappointing, with overall survival rates of ? 40% at 5 years. It is now well established that AML cells can evade the immune system through multiple mechanisms, including the expression of the enzyme indoleamine 2,3 dioxygenase. Immunotherapeutic strategies, including both active, such as vaccination with leukemia-associated antigens, and passive, such as adoptive transfer of allogeneic natural killer cells, may overcome leukemia escape and lead to improved cure. Allogeneic hemopoeitic stem cell transplantation, the most effective treatment of AML, is the best known model of immunotherapy. Following transplant, recipient AML cells are eradicated by donor immune cells through the graft-versus-leukemia (GVL) effect. However, GVL is clinically associated with graft-versus-host disease, the major cause of mortality after transplant. GVL is mediated by donor T cells recognizing either leukemia-associated antigens or minor as well as major histocompatibility antigens. Several innovative strategies have been devised to generate leukemia reactive T cells so as to increase GVL responses with no or little graft-versus-host disease. PMID:24341888

  13. Chemically induced leukemia in humans.

    PubMed Central

    Adamson, R H; Seiber, S M

    1981-01-01

    The human population may be exposed to potentially leukemogenic agents, either in the form of drugs and food additives or as environmental contaminants and pollutants. However, in spite of the large number and diversity of these chemicals, only a few have been implicated as human leukemogens. One such agent is benzene, a known bone marrow depressant. A number of case reports have associated chronic exposure to this agent with the development of acute leukemia, as have several epidemiologic surveys. Treatment with various antitumor agents, including procarbazine, melphalan, thio-TEPA, chlorambucil, and cyclophosphamide, has also been associated with the development of acute leukemia. In addition, chloramphenicol and phenylbutazone have been implicated as human leukemogens, but the association between exposure to these two agents and acute leukemia appears at present to be weaker than it is for benzene and antitumor agent exposure. Despite such associations between exposure to chemicals and acute leukemia, several important problems exist with regard to implicating specific agents in the development of this neoplasm in man, including the paucity of animal models for chemically induced leukemia, and the frequent necessity to rely on single case reports or clusters of cases in which chemical exposures are associated with acute leukemia. Future efforts should be directed at performing properly designed and well executed epidemiologic studies, and at developing new in vitro and in vivo models for the study of this neoplasm. PMID:6786872

  14. Molecular diagnosis of lymphoblastic leukemia.

    PubMed

    Goud, Kalal Iravathy; Dayakar, Seetha; Prasad, S V S S; Rao, Koteshwar N; Shaik, Amina; Vanjakshi, S

    2013-01-01

    The mixed lineage leukemia (MLL) gene at chromosome band 11q23 is commonly involved in reciprocal translocations that is detected in acute leukemia. The MLL gene, commonly known as mixed lineage leukemia or myeloid lymphoid leukemia, has been independently identified and cloned from the 11q23 breakpoint of acute leukemia. We describe a patient with acute lymphoblastic leukemia whose cells had shown reciprocal translocation between short arm (p21) of chromosome 2 and long arm (q23) of chromosome number 11 [t(2;11) (p21;q23)] by cytogenetic analysis. Fluorescence in situ hybridization analysis (FISH) was also performed for reconfirmation with a probe for MLL which showed split signals, hybridizing to both the derivative 2 and 11 chromosomes. Our study confirmed FISH as the most suitable assay for detecting MLL rearrangements because of its sensitivity and speed. It recommended that FISH should be used as complementary to conventional cytogenetic analysis. In conclusion, evaluation of the t(2;11)(p21;q23) was done by molecular clarification and flow cytometry. PMID:24125990

  15. 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 patients 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

  16. Sarcocystis fayeri-Induced Granulomatous and Eosinophilic Myositis in 2 Related Horses.

    PubMed

    Herd, H R; Sula, M M; Starkey, L A; Panciera, R J; Johnson, E M; Snider, T A; Holbrook, T C

    2015-11-01

    This report describes 2 genetically related paint mares, case Nos. 1 and 2, presented to the Oklahoma State University Boren Veterinary Medical Teaching Hospital for chronic weight loss and abnormal gait, respectively. Notable findings in both cases included marked persistent eosinophilia and multiple intramuscular lateral thoracic masses. Histologic examination of masses revealed eosinophilic, centrally necrotic granulomas and marked eosinophilic myositis. Granulomas in case No. 1 also contained intralesional Sarcocystis sp material, and adjacent muscle fibers contained intact protozoal cysts. Case No. 1 developed severe refractory muscle pain and recurrent esophageal dysphagia. At necropsy, disseminated, grossly visible granulomas were present throughout all examined striated muscles. Nested polymerase chain reaction of the 18S rRNA gene revealed >99% homology with Sarcocystis fayeri. Sarcocystis spp are apicomplexan protozoa that infect striated muscle of many omnivorous species, typically without inciting clinical disease. Sarcocystosis should be considered a rare cause of granulomatous eosinophilic myositis and choke in horses. PMID:25957356

  17. Elevation of serum surfactant protein-A with exacerbation in canine eosinophilic pneumonia.

    PubMed

    Sone, Katsuhito; Akiyoshi, Hideo; Hayashi, Akiyoshi; Ohashi, Fumihito

    2016-02-01

    A 7-year-old female spayed Labrador Retriever was admitted to our hospital, because of cough with sputum. She was diagnosed as having canine eosinophilic pneumonia (CEP) based on blood eosinophilia, bronchial pattern and infiltrative shadow observed on thoracic radiography, bronchiolar obstruction and air-space consolidation predominantly affecting the right caudal lung lobe, as revealed by computed tomography (CT), predominant eosinophils in CT-guided fine needle aspiration and the clinical course. She exhibited a good response to steroid therapy, and the cough disappeared. The serum surfactant protein (SP)-A level increased with the aggravated symptom and decreased markedly with improvement compared with the C-reactive protein level and the number of eosinophils. We propose that serum SP-A level is a good biomarker in CEP. PMID:26300438

  18. Elevation of serum surfactant protein-A with exacerbation in canine eosinophilic pneumonia

    PubMed Central

    SONE, Katsuhito; AKIYOSHI, Hideo; HAYASHI, Akiyoshi; OHASHI, Fumihito

    2015-01-01

    A 7-year-old female spayed Labrador Retriever was admitted to our hospital, because of cough with sputum. She was diagnosed as having canine eosinophilic pneumonia (CEP) based on blood eosinophilia, bronchial pattern and infiltrative shadow observed on thoracic radiography, bronchiolar obstruction and air-space consolidation predominantly affecting the right caudal lung lobe, as revealed by computed tomography (CT), predominant eosinophils in CT-guided fine needle aspiration and the clinical course. She exhibited a good response to steroid therapy, and the cough disappeared. The serum surfactant protein (SP)-A level increased with the aggravated symptom and decreased markedly with improvement compared with the C-reactive protein level and the number of eosinophils. We propose that serum SP-A level is a good biomarker in CEP. PMID:26300438

  19. Fibronectin changes in eosinophilic meningitis with blood-CSF barrier disruption.

    PubMed

    Shyu, Ling-Yuh; Hu, Ming-E; Chou, Chun-Hui; Chen, Ke-Min; Chiu, Ping-Sung; Lai, Shih-Chan

    2015-01-01

    Fibronectin, which is present at relatively low levels in healthy central nervous systems (CNS), shows increased levels in meningitis. In this study, fibronectin processing was correlated with the increased permeability of the blood-cerebrospinal fluid (CSF) barrier as well as with the formation of eosinophil infiltrates in angiostrongyliasis meningitis. The immunohistochemistry results show matrix metalloproteinase-9 (MMP-9) is localized in the choroid plexus epithelium. Coimmunoprecipitation demonstrated fibronectin strongly binds MMP-9. Furthermore, treatment with the MMP-9 inhibitor GM6001 significantly inhibited fibronectin processing, reduced the blood-CSF barrier permeability, and decreased the eosinophil counts. The decreased fibronectin processing in CSF implies decreased cellular invasion of the subarachnoid space across the blood-CSF barrier. Therefore, increased fibronectin processing may be associated with barrier disruption and participate in the extravasation and migration of eosinophils into the CNS during experimental parasitic infection. PMID:25660199

  20. The transcription factor XBP1 is selectively required for eosinophil differentiation

    PubMed Central

    Bettigole, Sarah E.; Lis, Raphael; Adoro, Stanley; Lee, Ann-Hwee; Spencer, Lisa A.; Weller, Peter F.; Glimcher, Laurie H.

    2015-01-01

    The transcription factor XBP1 has been linked to the development of highly secretory tissues such as plasma cells and Paneth cells, yet its function in granulocyte maturation has remained unknown. Here we discovered an unexpectedly selective and absolute requirement for XBP1 in eosinophil differentiation without an effect on the survival of basophils or neutrophils. Progenitors of myeloid cells and eosinophils selectively activated the endoribonuclease IRE1? and spliced Xbp1 mRNA without inducing parallel endoplasmic reticulum (ER) stress signaling pathways. Without XBP1, nascent eosinophils exhibited massive defects in the post-translational maturation of key granule proteins required for survival, and these unresolvable structural defects fed back to suppress critical aspects of the transcriptional developmental program. Hence, we present evidence that granulocyte subsets can be distinguished by their differential reliance on secretory-pathway homeostasis. PMID:26147683

  1. The transcription factor XBP1 is selectively required for eosinophil differentiation.

    PubMed

    Bettigole, Sarah E; Lis, Raphael; Adoro, Stanley; Lee, Ann-Hwee; Spencer, Lisa A; Weller, Peter F; Glimcher, Laurie H

    2015-08-01

    The transcription factor XBP1 has been linked to the development of highly secretory tissues such as plasma cells and Paneth cells, yet its function in granulocyte maturation has remained unknown. Here we discovered an unexpectedly selective and absolute requirement for XBP1 in eosinophil differentiation without an effect on the survival of basophils or neutrophils. Progenitors of myeloid cells and eosinophils selectively activated the endoribonuclease IRE1? and spliced Xbp1 mRNA without inducing parallel endoplasmic reticulum (ER) stress signaling pathways. Without XBP1, nascent eosinophils exhibited massive defects in the post-translational maturation of key granule proteins required for survival, and these unresolvable structural defects fed back to suppress critical aspects of the transcriptional developmental program. Hence, we present evidence that granulocyte subsets can be distinguished by their differential reliance on secretory-pathway homeostasis. PMID:26147683

  2. Eosinophils and mast cells as therapeutic targets in pediatric functional dyspepsia

    PubMed Central

    Friesen, Craig A; Schurman, Jennifer V; Colombo, Jennifer M; Abdel-Rahman, Susan M

    2013-01-01

    There is an increasing appreciation for the importance of inflammation as a pathophysiologic entity that contributes to functional gastrointestinal disorders including functional dyspepsia (FD). Importantly, inflammation may serve as a mediator between psychologic and physiologic functions. This manuscript reviews the literature implicating two inflammatory cell types, mast cells and eosinophils, in the generation of dyspeptic symptoms and explores their potential as targets for the treatment of FD. There are a number of inciting events which may initiate an inflammatory response, and the subsequent recruitment and activation of mast cells and eosinophils. These include internal triggers such as stress and anxiety, as well as external triggers such as microbes and allergens. Previous studies suggest that there may be efficacy in utilizing medications directed at mast cells and eosinophils. Evidence exists to suggest that combining anti-inflammatory medications with other treatments targeting stress can improve the rate of symptom resolution in pediatric FD. PMID:24199024

  3. Treatment of eosinophilic meningitis with a combination of prednisolone and mebendazole.

    PubMed

    Chotmongkol, Verajit; Sawadpanitch, Kookwan; Sawanyawisuth, Kittisak; Louhawilai, Sitichoke; Limpawattana, Panita

    2006-06-01

    To study the efficacy of the combination of prednisolone and mebendazole for the treatment of eosinophilic meningitis, we conducted a pilot study among Thai patients with eosinophilic meningitis. Patients were given a two-week course of prednisolone, 60 mg/day, and mebendazole, 10 mg/kg/day. The primary observation parameter was the number of patients who still had headaches after the two-week course of treatment. Forty-one patients were enrolled in the study. Four (10%) patients still had headaches after the two-week course of treatment and the median length of time until complete disappearance of headaches was three days. Serious side effects were not detected. Treatment for two weeks with the combination regimen of prednisolone and mebendazole is safe and beneficial in relieving headaches in patients with eosinophilic meningitis. PMID:16760531

  4. Radiation-induced eosinophilic, polymorphic, and pruritic eruption in a pig skin model

    PubMed Central

    Jang, Won Seok; Bae, Min Ji; Park, Sunhoo

    2015-01-01

    Eosinophilic, polymorphic and pruritic eruption associated with radiotherapy (EPPER) can occur in cancer patients after irradiation. In this study, we characterized the clinical and histopathological features of pig skin that developed widespread polymorphic and pruritic skin lesions following localized 50 Gy gamma-irradiation. The pigs developed pruritus 5-7 weeks after irradiation, and infiltration of the dermis by eosinophils was detected 4-7 weeks after irradiation. The irradiated animals also showed transiently increased numbers of peripheral eosinophils 5-7 weeks after treatment. Irradiation induced desquamation after 2-4 weeks, which and the desquamation gradually resolved after 7 weeks. These pathological changes correspond to those seen in irradiated human skin, indicating that this model could be useful for elucidating the pathogenesis of EPPER and for developing therapeutic and prophylactic methods. PMID:26755924

  5. Fungal chitin from asthma-associated home environments induces eosinophilic lung infiltration

    PubMed Central

    Van Dyken, Steven J.; Garcia, Daniel; Porter, Paul; Huang, Xiaozhu; Quinlan, Patricia J.; Blanc, Paul D.; Corry, David B.; Locksley, Richard M.

    2011-01-01

    Development of asthma and allergic inflammation involves innate immunity but the environmental contributions remain incompletely defined. Analysis of dust collected from the homes of asthmatic individuals revealed that the polysaccharide chitin is environmentally widespread, and associated with ?-glucans, possibly from ubiquitous fungi. Cell wall preparations of Aspergillus isolated from house dust induced robust recruitment of eosinophils into mouse lung, an effect that was attenuated by enzymatic degradation of cell wall chitinand ?-glucans. Mice expressing constitutively active acidic mammalian chitinase (AMCase) in the lungs demonstrated a significant reduction in eosinophil infiltration after fungal challenge. Conversely, chitinase inhibition prolonged the duration of tissue eosinophilia. Thus, fungal chitin derived from home environments associated with asthma induces eosinophilic allergic inflammation in the lung, and mammalian chitinases, including AMCase, limit this process. PMID:21824866

  6. Subcellular fractionation of human eosinophils: isolation of functional specific granules on isoosmotic density gradients.

    PubMed

    Neves, Josiane S; Perez, Sandra A C; Spencer, Lisa A; Melo, Rossana C N; Weller, Peter F

    2009-05-15

    Subcellular fractionation has been an important tool in investigating human eosinophil structure and function, including localizing of cytokine/chemokines within granules, investigating granule protein translocation and intracellular transport during eosinophil secretion, and studying secretory mechanisms of granules. The resolution of organelles obtained by subcellular fractionation was improved considerably after the introduction of nonionic iodinated density-gradient metrizamide and Nycodenz media that, unlike sucrose, exhibit relatively low tonicity throughout the gradient. However, the structure and membrane preservation of isolated organelles were still compromised due to the lack of gradient isoosmolarity. This paper describes a detailed protocol of subcellular fractionation of nitrogen cavitated eosinophils on an isoosmotic iodinated density gradient (iodixanol - OptiPrep) and the isolation of well preserved and functional membrane-bound specific granules. PMID:19328806

  7. 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

  8. In vitro study of histamine and histamine receptor ligands influence on the adhesion of purified human eosinophils to endothelium.

    PubMed

    Grosicki, Marek; W籀jcik, Tomasz; Chlopicki, Stefan; Kie-Kononowicz, Katarzyna

    2016-04-15

    It is a well-known fact that histamine is involved in eosinophil-dependent inflammatory responses including cellular chemotaxis and migration. Nevertheless, the relative role of histamine receptors in the mechanisms of eosinophils adhesion to endothelial cells is not known. Therefore the aim of presented study was to examine the effect of selective histamine receptors ligands on eosinophils adhesion to endothelium. For that purpose the highly purified human eosinophils have been isolated from the peripheral blood. The viability and functional integrity of isolated eosinophils have been validated in several tests. Histamine as well as 4-methylhistamine (selective H4 agonist) in concentration-dependent manner significantly increased number of eosinophils that adhere to endothelium. Among the selective histamine receptors antagonist or H1 inverse agonist only JNJ7777120 (histamine H4 antagonist) and thioperamide (dual histamine H3/H4 antagonist) had direct effect on eosinophils adhesion to endothelial cells. Antagonists of H1 (diphenhydramine, mepyramine) H2 (ranitidine and famotidine) and H3 (pitolisant) histamine receptors were ineffective. To the best of our knowledge, this is the first study to demonstrate that histamine receptor H4 plays a dominant role in histamine-induced eosinophils adhesion to endothelium. PMID:26939881

  9. Association between absolute blood eosinophil count and CKD stages among cardiac patients.

    PubMed

    Ishii, Rui; Fujita, Shu-Ichi; Kizawa, Shun; Sakane, Kazushi; Morita, Hideaki; Ozeki, Michishige; Sohmiya, Koichi; Hoshiga, Masaaki; Ishizaka, Nobukazu

    2016-02-01

    Elevated eosinophil count was shown to be associated with the development of cholesterol embolization syndrome, a potentially life-threatening condition, after catheter-based procedures. We investigated the association between stages of chronic kidney disease (CKD) and the absolute eosinophil count (AEC) among cardiac patients. CKD stages were determined solely on the estimated glomerular filtration rate or requirement for hemodialysis. Eosinophilia is defined as an eosinophil count exceeding 500/?L. A total of 1022 patients were enrolled in the current study, and eosinophil counts (/?L) in the first through fourth eosinophil count quartiles were <88, 88 to 154, 155 to <238, and 238?, respectively, and 29 patients (2.8%) had eosinophilia. Correlation coefficient between the AEC and age was -0.188 (P=0.001) in women and -0.042 (n.s.) in men (by Spearman's correlation test). Patients with higher CKD stages had a higher prevalence of the highest AEC quartile or eosinophilia. Logistic regression analysis using severe renal dysfunction (i.e., CKD stage 4 or 5) as the dependent variable, the highest AEC quartile had a significant positive association with an odds ratio of 1.99 (95% confidence interval, 1.20-3.31, P<0.01) after adjustment for sex, age, systolic blood pressure, and total white blood cell count. Similarly, after adjustment for the same variables, eosinophilia was associated with severe renal dysfunction with an odds ratio of 2.60 (95% confidence interval, 1.08-6.26, P<0.05). Eosinophil count was positively associated with higher CKD stages among cardiology patients, some fraction of which might be related to subclinical cholesterol embolization. PMID:25325991

  10. Prospective assessment of the diagnostic utility of esophageal brushings in adults with eosinophilic esophagitis.

    PubMed

    Kern, E; Lin, D; Larson, A; Yang, G-Y; Taft, T; Zalewski, A; Gonsalves, N; Hirano, I

    2016-01-01

    Patients with eosinophilic esophagitis (EoE) undergo multiple endoscopies with biopsy for both diagnosis and assessment of treatment response, which is inconvenient and costly. Brush cytology has been examined in Barrett's esophagus to reduce the need for repeated endoscopic biopsies. The aim of this pilot study was to evaluate the ability of brush cytology to detect mucosal eosinophilia in patients with EoE. This prospective study included adults with untreated and treated esophageal eosinophilia undergoing endoscopy at a tertiary care center. Patients received paired brushings and biopsies at the proximal and distal esophagus. A blinded pathologist quantified the number of eosinophils and epithelial cells per high-power field (hpf) on the cytology slides. The ratio of eosinophils/epithelial cells was used to normalize the cytology specimens for density of cells collected. The main outcome measures were sensitivity and specificity of brush cytology, and correlation between cytology and histology. Twenty-eight patients enrolled. The average age of the cohort was 37.7簣10.4 years; 75% of subjects were male. The sensitivity of cytology was 67-69% at the proximal esophagus and 70-72% at the distal esophagus. The specificity was 61-67% proximally and 70-75% distally. Histology was not significantly correlated with the max ratio of eosinophils/epithelial cells per hpf or the absolute number of eosinophils on cytology slides. Cytology using esophageal brushing has limited sensitivity and specificity for the detection of esophageal mucosal eosinophilia. The presence of exudates on endoscopy increased the detection of eosinophilia, which could make cytology useful in pediatric EoE, which often has a more exudative presentation. Diagnostic yield may improve with alternative acquisition techniques or the incorporation of eosinophil degranulation proteins. PMID:25515533

  11. Non-Eosinophilic Nasal Polyps Shows Increased Epithelial Proliferation and Localized Disease Pattern in the Early Stage

    PubMed Central

    Kim, Dong-Kyu; Jin, Hong Ryul; Eun, Kyoung Mi; Mutusamy, Somasundran; Cho, Seong H.; Oh, Sohee; Kim, Dae Woo

    2015-01-01

    Background Non-eosinophilic nasal polyps (NPs) show less inflammatory changes and are less commonly associated with lower airway inflammatory disorders such as asthma, compared with eosinophilic NPs. However, the development of non-eosinophilic NPs which is a predominant subtype in Asian population still remains unclear. Methods A total of 81 patients (45 with non-eosinophilic NPs and 36 with eosinophilic NPs) were enrolled. Clinical information and computed tomography (CT), endoscopic, and histological findings were investigated. Tissue samples were analyzed for total IgE levels and for mRNA expression levels of interleukin (IL)-4, IL5, IL13, interferon (IFN)-帠, tumor necrosis factor (TNF)-帢, IL-17A, IL22, IL-23p19, transforming growth factor (TGF)-帣1, TGF-帣2, TGF-帣3, and periostin. Immunostaining assessment of Ki67 as a proliferation marker was performed. Results We found that epithelial in-growing patterns such as pseudocysts were more frequently observed in histological and endoscopic evaluations of non-eosinophilic NPs, which was linked to increase epithelial staining of Ki67, a proliferating marker. Eosinophilic NPs were characterized by high infiltration of inflammatory cells, compared with non-eosinophilic NPs. To investigate the developmental course of each subtype, CT was analyzed according to CT scores and subtypes. Non-eosinophilic NPs showed more localized pattern and maxillary sinus involvement, but lesser olfactory involvement in early stage whereas eosinophilic NPs were characterized by diffuse ethmoidal and olfactory involvement. In addition, high ethmoidal/maxillary (E/M) CT scores, indicating ethmoidal dominant involvement, were one of surrogate markers for eosinophilic NP. E/M CT scores was positively correlated with levels of TH2 inflammatory markers, including IL4, IL5, periostin mRNA expression and total IgE levels in NPs, whereas levels of the TH1 cytokine, IFN- 帠 were inversely correlated. Moreover, if the combinatorial algorithm meet the three of the four markers, including IL5 (<2.379), periostin (<3.889), IFN-帠 (>0.316), and E/M ratio (<2.167), non-eosinophilic CRSwNP are diagnosed with a sensitivity of 84.4% and a specificity of 84.8%. Conclusion Histologic, immunologic and clinical data suggest that non-eosinophilic NPs showed enhanced epithelial alteration and more localized maxillary involvement. Combination of cutoff value on IL5, periostin, IFN-帠, and E/M scores may be one of surrogate markers for non-eosinophil NP subtype. PMID:26439628

  12. Automated image analysis in the study of lymphocyte subpopulation in eosinophilic oesophagitis

    PubMed Central

    2014-01-01

    Background Eosinophilic oesophagitis (EoE) is characterized by the presence of eosinophils in oesophageal mucosa. Other inflammatory cells, mainly lymphocytes, dendritic cells, and mast cells may also play an important role in this disease. The aim of this study is to compare the inflammatory pattern of the mucosa between EoE and gastro-oesophageal reflux disease (GERD), using automatic image analysis in digital slides, and to assess treatment response after elimination diet and food challenge test. Methods From 2010 to 2013, 35 oesophageal biopsies from EoE and GERD patients were randomly selected. In six EoE biopsies, patients had been treated with selective food exclusion diet. Immunohistochemical study with CD3, CD20, CD4, and CD8 for lymphocyte populations, CD1a for dendritic cells, and CD117/c-kit for mast cells was performed. Slides were scanned using Leica Aperio Scanscope XT with 40 magnification. Immunohistochemical expression was quantified in 245 immunohistochemistry digital slides with Leica Aperio positive pixel count algorithm using two different approaches: whole slide analysis versus selection of a 2 mm2 hot spot area. Results Average eosinophil cell count was significantly higher (p < 0.001) in the first biopsy of EoE patients before treatment (30.75 eosinophils per high power field - HPF) than in GERD patients (0.85 eosinophils/HPF) or in EoE patients after treatment with elimination diet (1.60 eosinophils/HPF). In the immunohistochemical study, manual count and automatic image analysis showed a significant increase in the number of CD3 and CD8 cells in EoE patients, compared with GERD patients. However, the increase of CD117/c-kit was only statistically significant when manual counting procedures were used. CD20 positive cell count also showed a non-statistically significant tendency to reduce after elimination diet treatment. Manual eosinophil count correlated much better with CD3 and CD8 count using hot spot approach than with a whole slide approach. Conclusions Positive pixel count algorithm can be a useful tool to quantify the immunohistochemical expression of inflammatory cells in the diagnosis and follow up of eosinophilic oesophagitis. PMID:25565117

  13. Role of Endoscopy in Diagnosis and Management of Pediatric Eosinophilic Esophagitis.

    PubMed

    Muir, Amanda B; Merves, Jamie; Liacouras, Chris A

    2016-01-01

    Eosinophilic esophagitis (EoE) is a chronic allergic (immune-mediated) disease that leads to esophageal dysfunction and feeding disorders in children. Foods, and possibly environmental triggers, cause an inflammatory response in the esophagus, leading to esophageal inflammation, eosinophilic infiltration, and esophageal dysmotility, which may progress to dysphagia, food impaction, and esophageal stricture. Endoscopy with biopsy and histologic evaluation is currently the only method to diagnose EoE. Once diagnosed with EoE, children undergo follow-up endoscopy after therapy initiation and adjustments to ensure remission. Furthermore, children with food impactions or strictures may require endoscopic intervention such as foreign body removal and/or esophageal dilation. PMID:26616904

  14. Pharmacological and immunohistochemical evidence for a functional nitric oxide synthase system in rat peritoneal?eosinophils

    PubMed Central

    Zanardo, Renata C. O.; Costa, Edmar; Ferreira, Heloisa H. A.; Antunes, Edson; Martins, Antonio R.; Murad, Ferid; De Nucci, Gilberto

    1997-01-01

    Eosinophil migration in vivo is markedly attenuated in rats treated chronically with the NO synthase (NOS) inhibitor N?-nitro-l-arginine methyl ester (l-NAME). In this study, we investigated the existence of a NOS system in eosinophils. Our results demonstrated that rat peritoneal eosinophils strongly express both type II (30.2 11.6% of counted cells) and type III (24.7 7.4% of counted cells) NOS, as detected by immunohistochemistry using affinity purified mouse mAbs. Eosinophil migration in vitro was evaluated by using 48-well microchemotaxis chambers and the chemotactic agents used were N-formyl-methionyl-leucyl-phenylalanine (fMLP, 5 10?8 M) and leukotriene B4 (LTB4, 10?8 M). l-NAME (but not d-NAME) significantly inhibited the eosinophil migration induced by both fMLP (54% reduction for 1.0 mM; P < 0.05) and LTB4 (61% reduction for 1.0 mM; P < 0.05). In addition, the type II NOS inhibitor 2-amino-5,6-dihydro-6-methyl-4H-1,3-thiazine and the type I/II NOS inhibitor 1-(2-trifluoromethylphenyl) imidazole also markedly (P < 0.05) attenuated fMLP- (52% and 38% reduction for 1.0 mM, respectively) and LTB4- (52% and 51% reduction for 1.0 mM, respectively) induced migration. The inhibition of eosinophil migration by l-NAME was mimicked by the soluble guanylate cyclase inhibitor 1H-[1,2,4] oxadiazolo [4,3,-a] quinoxalin-1-one (0.01 and 0.1 mM) and reversed by either sodium nitroprusside (0.1 mM) or dibutyryl cyclic GMP (1 mM). We conclude that eosinophils do express NO synthase(s) and that nitric oxide plays an essential role in eosinophil locomotion by acting through a cyclic GMP transduction mechanism. PMID:9391161

  15. Enterolithiasis complicating eosinophilic enteritis: A case report and review of literature

    PubMed Central

    Shivathirthan, Nairuthya; Maheshwari, Gaurav; Kamath, Dinesh; Haldar, Premashish

    2009-01-01

    We report a case of eosinophilic enteritis involving the proximal small bowel, a relatively rare entity, presenting unusually as enteroliths in a 68-year-old man with complaints of anemia, malena and abdominal pain. The disease if diagnosed in the initial stages responds well to medical treatment but if associated with complications or misdiagnosed, surgical modality is the treatment of choice. In our case, the patient presented with enteroliths and strictures. Resection and anastomosis of the small bowel containing stones was carried out. Histopathology confirmed the diagnosis as eosinophilic enteritis. PMID:21160800

  16. PedsQL Eosinophilic Esophagitis Module: Feasibility, Reliability and Validity

    PubMed Central

    Franciosi, James P.; Hommel, Kevin A.; Bendo, Cristiane B.; King, Eileen C.; Collins, Margaret H.; Eby, Michael D.; Marsolo, Keith; Abonia, J. Pablo; von Tiehl, Karl F.; Putnam, Philip E.; Greenler, Alexandria J.; Greenberg, Allison B.; Bryson, Ronald A.; Davis, Carla M.; Olive, Anthony P.; Gupta, Sandeep K.; Erwin, Elizabeth A.; Klinnert, Mary D.; Spergel, Jonathan M.; Denham, Jolanda M.; Furuta, Glenn T.; Rothenberg, Marc E.; Varni, James W.

    2014-01-01

    Objective Eosinophilic esophagitis (EoE) is a chronic esophageal inflammatory condition with a paucity of information on health-related quality of life (HRQOL). The objective of the study was to report on the measurement properties of the PedsQL EoE Module. Methods The PedsQL EoE Module was completed in a multisite study by 196 pediatric EoE patients and 262 EoE parents. Results The PedsQL EoE Module scales evidenced excellent feasibility (0.6%3.1% missing), excellent group comparison reliability across total scale scores (patient ? = 0.93; parent proxy ? = 0.94), good reliability for the seven individual scales (patient ? = 0.750.87; parent proxy ? = 0.810.92), excellent test-retest reliability (patient ICC = 0.88; parent ICC= 0.82), demonstrated no floor effects and low ceiling effects, and demonstrated a high percentage of scaling success for most scales. Intercorrelations with the PedsQL Generic Core Scales were in the medium (0.30) to large (0.50) range. PedsQL EoE Module scores were worse among patients with active histologic disease (> 5 eos/hpf) compared to those in remission (patient self-report: 63.3 vs. 69.9 [p<0.05]; parent proxy-report: 65.1 vs. 72.3 [p<0.01]), and those treated with dietary restrictions compared to those with no restrictions (patient self-report: 61.6 vs. 74.3 [p< 0.01]; parent proxy-report: 65.5 vs. 74.7 [p<0.01]). Conclusions The results demonstrate excellent measurement properties of the PedsQL EoE Module. Patients with active histologic disease and those treated with dietary restrictions demonstrated worse PedsQL scores. The PedsQL EoE Module may be utilized in evaluation of pediatric EoE disease-specific HRQOL in clinical research and practice. PMID:23478422

  17. Effectiveness of Dietary Allergen Exclusion Therapy on Eosinophilic Colitis in Chinese Infants and Young Children 3 Years of Age

    PubMed Central

    Yang, Min; Geng, Lanlan; Chen, Peiyu; Wang, Fenghua; Xu, Zhaohui; Liang, Cuiping; Li, Huiwen; Fang, Tiefu; Friesen, Craig A.; Gong, Sitang; Li, Dingyou

    2015-01-01

    Eosinophilic colitis is a well recognized clinical entity mainly associated with food allergies. Empiric treatment options include dietary allergen exclusion (extensively hydrolyzed protein formula and elimination diet), anti-allergy medications (antihistamines and leukotriene receptor antagonists) and corticosteroids. We evaluated the effectiveness of dietary antigen exclusion on clinical remission of eosinophilic colitis in infants and young children. We retrospectively reviewed charts of all infants and children 3 years of age who were diagnosed with eosinophilic colitis (defined as mucosal eosinophilia 20 hpf1) from 1 January 2011 to 31 December 2013 at a tertiary childrens hospital in China. Forty-nine children were identified with eosinophilic colitis. Elemental formula, simple elimination diet or combination therapy resulted in clinical improvement in 75%, 88.2% and 80% of patients, respectively. In conclusion, eosinophilic colitis in infants and children 3 years of age responded well to dietary allergen exclusion. PMID:25768952

  18. 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

  19. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis.

    PubMed

    Obiozor, Cynthia; Ganguly, Siddhartha; Fraga, Garth R

    2015-01-01

    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. PMID:26437164

  20. Eosinophilic Fasciitis: What Matters in Management in a Developing CountryA Case Report with Two and a Half-year Follow-up

    PubMed Central

    Islam, Md. Ariful; Abdal, Syed Jamil; Azad, Mohammad Abul Kalam; Ahmedullah, Abul Khair; Haq, Syed Atiqul

    2012-01-01

    Eosinophilic fasciitis is an uncommon disorder of unknown aetiology and poorly-understood pathogenesis. Since 1974, over 250 cases of eosinophilic fasciitis have been reported worldwide. The first case of eosinophilic fasciitis from Bangladesh is reported here. The challenges of diagnosis, treatment, and follow-up, including family and social support, are discussed. PMID:22524129