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Sample records for granulocytic ehrlichia infection

  1. Serologic evidence of infection with granulocytic ehrlichiae in black bears in Pennsylvania.

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    Schultz, Sharon M; Nicholson, William L; Comer, James A; Childs, James E; Humphreys, Jan G

    2002-01-01

    Serum samples from 381 black bears (Ursus americanus) killed in Pennsylvania (USA) on 24 November 1997 were analyzed for antibodies reactive to the agent of human granulocytic ehrlichiosis (HGE; Ehrlichia sp.) by indirect immunofluorescence assay. Antibody reactivity to HGE antigen was detected in 21% (81/381) of the samples collected. Reactive samples were reported from 56% (14/25) of the counties where bear samples were collected. Endpoint antibody titer ranged from 1:8 to 1:16, 192, with a geometric mean titer of 1:582. There was no significant difference in antibody prevalence between male and female bears (P bears were significantly more likely to have reactive antibodies than juvenile bears (P bear blood clots (n = 181) through nested polymerase chain reaction assays were unsuccessful. Further studies are needed for identification of the pathogen-responsible for induction of HGE-reactive. This is the first description of antibodies reactive to the HGE agent in black bears and suggests these mammals are infected with the agent of HGE or an antigenically related ehrlichial species.

  2. Antibodies to granulocytic ehrlichiae in white-footed and cotton mice in eastern United States.

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    Magnarelli, L A; Stafford, K C; Ijdo, J W; Fikrig, E; Oliver, J H; Hutcheson, H J; Boone, J L

    1999-04-01

    Serum samples, collected from Peromyscus leucopus (white-footed mouse) or Peromyscus gossypinus (cotton mouse) during 1987 through 1990 in Florida, Georgia, Maryland, Mississippi, and North Carolina (USA), and in 1997 in southern Connecticut were analyzed by indirect fluorescent antibody (IFA) staining methods or Western blot procedures for antibodies to granulocytic ehrlichiae. Of the 82 sera from white-footed mice in Connecticut tested by IFA methods with either the BDS or NCH-1 strain of the human granulocytic ehrlichiosis (HGE) agent, 45 (55%) and 42 (51%) of the samples contained antibodies to these strains, respectively, at concentrations ranging from 1:80 to 1:2560. One (2%) of 43 sera from P. leucopus captured in Assateague Island (Maryland) had a titer of 1:80, while three (20%) of 15 sera from P. gossypinus, captured in Sapelo Island (Georgia) and four (40%) of 10 sera from cotton mice caught in Amelia Island (Florida) had antibodies to the NCH-1 strain at titers of 1:160 to 1:1,280. Fifty-five sera from P. leucopus in Cape Hatteras (North Carolina) and 30 sera from P. gossypinus in Mississippi were negative. Western blot analyses confirmed seropositivity for 19 (95%) of 20 mouse sera positive by IFA staining methods, including samples from both mouse species captured in Connecticut, Maryland, or Florida. There were key banding patterns to proteins having molecular masses of about 44, 80, 105, 110, or 120 kDa. Both serologic assays can be used to determine if mice have been exposed to granulocytic ehrlichiae. These rodents also may be useful in surveillance programs to identify endemic sites for HGE and in performing laboratory studies on immune responses to the etiologic agent.

  3. Anaplasma, Ehrlichia and Rickettsia species infections in cats

    NARCIS (Netherlands)

    Pennisi, Maria Grazia; Hofmann-Lehmann, Regina; Radford, Alan D; Tasker, Séverine; Belák, Sándor; Addie, Diane D; Boucraut-Baralon, Corine; Egberink, Herman; Frymus, Tadeusz; Gruffydd-Jones, Tim; Hartmann, Katrin; Horzinek, Marian C; Hosie, Margaret J; Lloret, Albert; Lutz, Hans; Marsilio, Fulvio; Thiry, Etienne; Truyen, Uwe; Möstl, Karin

    2017-01-01

    OVERVIEW: Anaplasma species, Ehrlichia species and Rickettsia species are vector-borne pathogens infecting a wide variety of mammals, but causing disease in very few of them. Infection in cats: Anaplasma phagocytophilum is the most important feline pathogen among these rickettsial organisms, and

  4. NNDSS - Table II. Ehrlichiosis and Anaplasmosis, Anaplasma phagocytophilum infection to Ehrlichia chaffeensis infection

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Ehrlichiosis and Anaplasmosis, Anaplasma phagocytophilum infection to Ehrlichia chaffeensis infection - 2018. In this Table, provisional cases of...

  5. Seroprevalence of Ehrlichia canis infection in stray dogs from Serbia

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    Nataša Bogićević

    2017-03-01

    Full Text Available Canine Monocytic Ehrlichiosis is a zoonotic bacterial disease with worldwide distribution. With regards to the population of stray dogs, the disease is facilitated due to their lifestyle and the lack of anti-parasitic protection. The aim of this study was to provide serological data on the presence of a specific Ehrlichia canis IgG antibodies in stray dogs, originating from 7 municipalities in Serbia. During the period from April 2013 to June 2014, 217 canine sera were submitted to the laboratory of the Department of Infectious Diseases of Animals and Bees, Faculty of Veterinary Medicine in Belgrade. An immunofluorescent antibody test (IFAT was performed to detect antibodies to Ehrlichia canis (cut off, 1:50. Seropositive dogs were found in 5 out of 7 counties with a seroprevalence varying from 3.57% to 20% and an overall seroprevalence of 11.06% (24/217. There was no statistically significant difference between the prevalence of infection and the host age or gender. Results showed that stray dogs contribute to maintaining and spreading of Ehrlichia canis in Serbia. Due to the close relationship between people and dogs, it is of great importance to constantly monitor and improve prevention of this disease.

  6. NNDSS - Table II. Ehrlichiosis and Anaplasmosis, Ehrlichia ewingii infection to Undetermined

    Data.gov (United States)

    U.S. Department of Health & Human Services — NNDSS - Table II. Ehrlichiosis and Anaplasmosis, Ehrlichia ewingii infection to Undetermined - 2018. In this Table, provisional cases of selected notifiable diseases...

  7. Molecular epidemiology of heartwater (Ehrlichia ruminantium infection) in The Gambia

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    Faburay, B.

    2007-01-01

    Heartwater is caused by Ehrlichia ruminantium and transmitted by ticks of the genus Amblyomma. It occurs in sub-Saharan Africa and in the Caribbean and affects domestic ruminants. There is general lack of information on the epidemiology of the disease in The Gambia. Results of a countrywide

  8. The Microbiome of Ehrlichia-Infected and Uninfected Lone Star Ticks (Amblyomma americanum.

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    R T Trout Fryxell

    Full Text Available The Lone Star tick, Amblyomma americanum, transmits several bacterial pathogens including species of Anaplasma and Ehrlichia. Amblyomma americanum also hosts a number of non-pathogenic bacterial endosymbionts. Recent studies of other arthropod and insect vectors have documented that commensal microflora can influence transmission of vector-borne pathogens; however, little is known about tick microbiomes and their possible influence on tick-borne diseases. Our objective was to compare bacterial communities associated with A. americanum, comparing Anaplasma/Ehrlichia -infected and uninfected ticks. Field-collected questing specimens (n = 50 were used in the analyses, of which 17 were identified as Anaplasma/Ehrlichia infected based on PCR amplification and sequencing of groEL genes. Bacterial communities from each specimen were characterized using Illumina sequencing of 16S rRNA gene amplicon libraries. There was a broad range in diversity between samples, with inverse Simpson's Diversity indices ranging from 1.28-89.5. There were no statistical differences in the overall microbial community structure between PCR diagnosed Anaplasma/Ehrlichia-positive and negative ticks, but there were differences based on collection method (P < 0.05, collection site (P < 0.05, and sex (P < 0.1 suggesting that environmental factors may structure A. americanum microbiomes. Interestingly, there was not always agreement between Illumina sequencing and PCR diagnostics: Ehrlichia was identified in 16S rRNA gene libraries from three PCR-negative specimens; conversely, Ehrlichia was not found in libraries of six PCR-positive ticks. Illumina sequencing also helped identify co-infections, for example, one specimen had both Ehrlichia and Anaplasma. Other taxa of interest in these specimens included Coxiella, Borrelia, and Rickettsia. Identification of bacterial community differences between specimens of a single tick species from a single geographical site indicates that

  9. Autologous 111In-oxine-labeled granulocytes in Yersinia infections

    International Nuclear Information System (INIS)

    Becker, W.; Boerner, W.; Fischbach, W.

    1985-01-01

    Autologous 111 In-oxine-labeled granulocytes have proved to be valuable for the localization of inflammatory bowel diseases, especially Crohn's disease and ulcerative colitis. Other rare inflammatory bowel diseases also yield positive 111 In scans. One case of Yersinia infection of the terminal ileum (Yersinia enterocolitica) showing an accumulation of 111 In-oxine-labeled granulocytes 0.5, 4, and 24 h after the reinjection of the labeled cells is described. The 4-day fecal excretion of 111 In-oxine granulocytes showed a slight inflammatory activity of the terminal ileum. One negative scan is reported in a cotrimoxazole-treated patient with Yersinia infection. (orig.)

  10. Novel Ehrlichia and Hepatozoon agents infecting the crab-eating fox (Cerdocyon thous) in southeastern Brazil.

    Science.gov (United States)

    Almeida, Aliny P; Souza, Tayse D; Marcili, Arlei; Labruna, Marcelo B

    2013-05-01

    This study evaluated infection by vector-borne agents in 58 crab-eating fox (Cerdocyon thous L.) that were road-killed in an Atlantic rainforest reserve in the state of Espírito Santo, southeastern Brazil. Spleen, lung, or blood samples collected from the foxes were tested in the laboratory by a battery of polymerase chain reaction (PCR) assays targeting bacteria of the genera Rickettsia, Borrelia, Coxiella, Anaplasma, and Ehrlichia; and protozoa of the genera Babesia, Hepatozoon, and Leishmania. Of the targeted organisms, evidence of infection in the foxes was detected for Ehrlichia and Hepatozoon organisms only. Overall, six (10.3%) foxes were infected by an ehrlichial agent closely related to an ehrlichial agent recently detected in free-ranging Jaguars [(Panthera onca (L.)] in central-western Brazil, and to Ehrlichia ruminantium. For Hepatozoon, 28 (48.3%) foxes were infected by an agent closely related to Hepatozoon sp. Curupira 2 and H. americanum; and one (1.7%) fox was infected by an organism closely related to reptile-associated Hepatozoon agents. Finally, 11 (19.0%) foxes were found infested by Amblyomma cajennense (F.) nymphs, which were all PCR negative for the range of vector-borne agents cited above. Because the haplotypes found in free-ranging foxes are genetically closely related to pathogens of great veterinary importance, namely E. ruminantium and H. americanum, it is highly desirable to know if these novel organisms have any important role as agents of diseases in domestic animals and wildlife in Brazil.

  11. Case report of canine co-infection with Leishmania infantum and Ehrlichia canis

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    Stefanovska Jovana

    2011-05-01

    Full Text Available Canine leishmaniasis (CanL due to Leishmania infantum and canine monocytic ehrilichiosis (CME due to Ehrlichia canis are common diseases with zoonotic potential in the Mediterranean area. Their prevalence in R. Macedonia as a neighboring Mediterranean county is expected. In both diseases similar clinical symptoms can be manifested in dogs such as: lethargy, anorexia, weight loss, epistaxis, fever, pale mucous membranes, enlarged lymph nodes, splenomegaly, ocular signs. This case report present an atypical case of 11 year old female Samoyed with starting single clinical symptom epistaxys. Initial diagnostic procedures revealed the presence only of CanL, which was diagnosed using indirect immunofluorescence method and ELISA. First laboratory findings showed normal hematological and renal profiles. Dog was put on a treatment with Allopurinol (20mg/kg, p/o for at least 9 months. Termination of the therapy after 6 months brought a numerous clinical symptoms involving weakness, dehydration, pale mucous membranes lost pupilar reflex, uremic breath and biochemical parameters revealed a renal failure. Using a commercial ELISA kit Ehrlichia canis as a co infection was diagnosed. Most probably the second infectious agent was induced in the past 6 months, causing more severe pathological effects than CanL infection alone.

  12. High infection of Anaplasma and Ehrlichia spp. among tick species collected from different geographical locations of Iran

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    Leila Tajedin

    2016-10-01

    Full Text Available Objective: To ascertain the prevalence of the Anaplasma/Ehrlichia infections in tick population within four provinces of Iran. Methods: A total of 384 tick specimens were collected from domestic animals inhabiting in four provinces (East Azerbaijan, Gilan, South Khorasan and Yazd. Specimens were identified based on morphological analysis. The detection of Anaplasma spp./Ehrlichia spp. within tick samples was carried out by nested PCR amplification of the 16S ribosomal RNA gene accompanied by DNA sequencing and analysis for verification. Results: A total of 10 tick species were identified as follows: Ornithodoros lahorensis (O. lahorensis (44.8%, Hyalomma dromedarii (15.6%, Dermacentor marginatus (13.5%, Hyalomma anatolicum (11.2%, Hyalomma asiaticum (5.7%, Hyalomma marginatum (4.9%, Rhipicephalus sanguineus (2.3%, Hyalomma detritum (1.0%, Dermacentor niveus (0.5% and Argas persicus (0.3%. The percentage distribution of Anaplasma/Ehrlichia was 55.5% (213 across 384 studied ticks. Conclusions: To the best of our knowledge, this is the first report of Anaplasma ovis infection in O. lahorensis in Iran. We also conjecture the prevalence of Ehrlichia spp. in Yazd Province based on sequencing results; also, it is suggested that O. lahorensis is a potential vector in the studied area. This survey highlights the importance of Argasidae family to verify and correlate their threat in causing anaplasmosis and other diseases in animals.

  13. Association between canine leishmaniosis and Ehrlichia canis co-infection: a prospective case-control study.

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    Attipa, Charalampos; Solano-Gallego, Laia; Papasouliotis, Kostas; Soutter, Francesca; Morris, David; Helps, Chris; Carver, Scott; Tasker, Séverine

    2018-03-20

    In the Mediterranean basin, Leishmania infantum is a major cause of disease in dogs, which are frequently co-infected with other vector-borne pathogens (VBP). However, the associations between dogs with clinical leishmaniosis (ClinL) and VBP co-infections have not been studied. We assessed the risk of VBP infections in dogs with ClinL and healthy controls. We conducted a prospective case-control study of dogs with ClinL (positive qPCR and ELISA antibody for L. infantum on peripheral blood) and clinically healthy, ideally breed-, sex- and age-matched, control dogs (negative qPCR and ELISA antibody for L. infantum on peripheral blood) from Paphos, Cyprus. We obtained demographic data and all dogs underwent PCR on EDTA-blood extracted DNA for haemoplasma species, Ehrlichia/Anaplasma spp., Babesia spp., and Hepatozoon spp., with DNA sequencing to identify infecting species. We used logistic regression analysis and structural equation modelling (SEM) to evaluate the risk of VBP infections between ClinL cases and controls. From the 50 enrolled dogs with ClinL, DNA was detected in 24 (48%) for Hepatozoon spp., 14 (28%) for Mycoplasma haemocanis, 6 (12%) for Ehrlichia canis and 2 (4%) for Anaplasma platys. In the 92 enrolled control dogs, DNA was detected in 41 (45%) for Hepatozoon spp., 18 (20%) for M. haemocanis, 1 (1%) for E. canis and 3 (3%) for A. platys. No Babesia spp. or "Candidatus Mycoplasma haematoparvum" DNA was detected in any dog. No statistical differences were found between the ClinL and controls regarding age, sex, breed, lifestyle and use of ectoparasitic prevention. A significant association between ClinL and E. canis infection (OR = 12.4, 95% CI: 1.5-106.0, P = 0.022) was found compared to controls by multivariate logistic regression. This association was confirmed using SEM, which further identified that younger dogs were more likely to be infected with each of Hepatozoon spp. and M. haemocanis, and dogs with Hepatozoon spp. were more likely to

  14. Leishmania, Babesia and Ehrlichia in urban pet dogs: co-infection or cross-reaction in serological methods?

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    Felipe da Silva Krawczak

    2015-02-01

    Full Text Available INTRODUCTION: The present study was designed to assess the occurrence of co-infection or cross-reaction in the serological techniques used for detecting the anti-Leishmania spp., -Babesia canis vogeli and -Ehrlichia canis antibodies in urban dogs from an area endemic to these parasites. METHODS: The serum samples from dogs were tested for the Babesia canis vogeli strain Belo Horizonte antigen and Ehrlichia canis strain São Paulo by immunofluorescence antibody test (IFAT and by anti-Leishmania immunoglobulin G (IgG antibody detection to assess Leishmania infection. We used the following four commercial kits for canine visceral leishmaniasis: ELISA, IFAT, Dual Path Platform (DPP (Bio Manguinhos(r/FIOCRUZ/MS and a rK39 RDT (Kalazar Detect Canine Rapid Test; Inbios. RESULTS : Of 96 serum samples submitted to serological assays, 4 (4.2% were positive for Leishmania as determined by ELISA; 12 (12.5%, by IFAT; 14 (14.6% by rK39 RDT; and 20 (20.8%, by DPP. Antibodies against Ehrlichia and Babesia were detected in 23/96 (23.9% and 30/96 (31.2% samples, respectively. No significant association was identified between the results of tests for detecting Babesia or Ehrlichia and those for detecting Leishmania (p-value>0.05. CONCLUSIONS: In the present study, we demonstrated co-infection with Ehrlichia or Babesia and Leishmania in dogs from Minas Gerais (Brazil; we also found that the serological tests that were used did not cross-react.

  15. Babesia canis vogeli, Ehrlichia canis, and Anaplasma platys infection in a dog.

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    Al Izzi, Salah; Martin, Donald S; Chan, Roxanne Y Y; Leutenegger, Christian M

    2013-12-01

    A 12-month-old male neutered mixed breed dog was presented with a history of diarrhea, lethargy, emaciation, polydypsia, and sniffling. Physical examination findings included pale mucous membranes, increased heart and respiratory rates, and normal rectal temperature (38°C). Hematologic abnormalities included anemia and thrombocytopenia. Biochemical abnormalities included hypoalbuminemia, hyperbilirubinemia, and elevated ALP and ALT activities. A SNAP 4Dx test result was positive for Ehrlichia canis. Babesia canis vogeli organisms were found in the peripheral blood films, while morulae of E canis were not seen. Real-time polymerase chain reaction testing confirmed the presence of both B c vogeli and E canis organisms, and also was positive for Anaplasma platys infection. The dog recovered following treatment with doxycycline and imidocarb dipropionate, with normal hematology and biochemical profiles. © 2013 American Society for Veterinary Clinical Pathology.

  16. Mixed Ehrlichia canis, Hepatozoon canis, and presumptive Anaplasma phagocytophilum infection in a dog.

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    Mylonakis, Mathio E; Koutinas, Alex F; Baneth, Gad; Polizopoulou, Zoe; Fytianou, Anna

    2004-01-01

    A 5-month-old, female, mongrel dog was admitted to the Clinic of Companion Animal Medicine, Aristotle University of Thessaloniki, Greece, with depression, anorexia, fever, peripheral lymphadenopathy, splenomegaly, oculonasal discharge, nonregenerative anemia, and mild thrombocytopenia. Cytology of Giemsa-stained buffy coat, bone marrow, and lymph node aspiration smears revealed numerous morulae in mononuclear leukocytes and in neutrophils, and Hepatozoon canis gamonts in neutrophils. The dog was seropositive to Ehrlichia canis (immunofluorescence assay [IFA]) and Hepatozoon canis (ELISA) but not to Anaplasma phagocytophilum (IFA). A nested polymerase chain reaction performed on bone marrow aspirates was positive for E canis. This method was not applied for the detection of A phagocytophilum. Treatment with doxycycline and imidocarb dipropionate resulted in both clinical and parasitologic cure. This is the first reported case of a mixed infection with E canis, H canis, and presumptive A phagocytophilum. The findings emphasize the value of cytology in offering a quick and inexpensive diagnosis in mixed tick-borne infections of dogs.

  17. Granulocytes in Helminth Infection - Who is Calling the Shots?

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    Makepeace, BL; Martin, C; Turner, JD; Specht, S

    2012-01-01

    Helminths are parasitic organisms that can be broadly described as “worms” due to their elongated body plan, but which otherwise differ in shape, development, migratory routes and the predilection site of the adults and larvae. They are divided into three major groups: trematodes (flukes), which are leaf-shaped, hermaphroditic (except for blood flukes) flatworms with oral and ventral suckers; cestodes (tapeworms), which are segmented, hermaphroditic flatworms that inhabit the intestinal lumen; and nematodes (roundworms), which are dioecious, cylindrical parasites that inhabit intestinal and peripheral tissue sites. Helminths exhibit a sublime co-evolution with the host´s immune system that has enabled them to successfully colonize almost all multicellular species present in every geographical environment, including over two billion humans. In the face of this challenge, the host immune system has evolved to strike a delicate balance between attempts to neutralize the infectious assault versus limitation of damage to host tissues. Among the most important cell types during helminthic invasion are granulocytes: eosinophils, neutrophils and basophils. Depending on the specific context, these leukocytes may have pivotal roles in host protection, immunopathology, or facilitation of helminth establishment. This review provides an overview of the function of granulocytes in helminthic infections. PMID:22360486

  18. Canine vector-borne co-infections: Ehrlichia canis and Hepatozoon canis in the same host monocytes.

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    Baneth, Gad; Harrus, Shimon; Gal, Arnon; Aroch, Itamar

    2015-02-28

    The protozoon Hepatozoon canis and the rickettsia Ehrlichia canis are tick-borne pathogens, transmitted by Rhipicephalus sanguineus, which cause canine hepatozoonosis and canine monocytic ehrlichiosis, respectively. Co-infection of the same host monocytes with H. canis and E. canis confirmed by molecular characterization of the infecting agents and quantitative assessment of co-infected cells is described for the first time in three naturally-infected dogs. Blood smear evaluation indicated that at least 50% of the leukocytes infected with H. canis gamonts contained E. canis morulae. Co-infection of the same host cell demonstrated in this report suggests that infection with one pathogen may permit or enhance invasion or prolonged cellular survival of the other. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. A molecular epidemiological survey of Babesia, Hepatozoon, Ehrlichia and Anaplasma infections of dogs in Japan

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    KUBO, Shotaro; TATENO, Morihiro; ICHIKAWA, Yasuaki; ENDO, Yasuyuki

    2015-01-01

    Tick-borne diseases are often encountered in canine clinical practice. In the present study, a molecular epidemiological survey of dogs in Japan was conducted to understand the prevalence and geographical distribution of Babesia spp., Hepatozoon spp., Ehrlichia spp. and Anaplasma spp. Pathogen-derived DNA in blood samples obtained from 722 dogs with a history of exposure to ticks and/or fleas was examined by PCR. The prevalence of Babesia gibsoni, Babesia odocoilei-like species, Hepatozoon canis and Ehrlichia spp./Anaplasma spp. was 2.4% (16/722), 0.1% (1/722), 2.5% (18/722) and 1.5% (11/722), respectively. While B. gibsoni and Ehrlichia spp./Anaplasma spp. were detected in the western part of Japan, H. canis was detected in Tohoku area in addition to western and central parts of Japan. PMID:25947226

  20. Neospora caninum and Ehrlichia canis co-infection in a dog with meningoencephalitis.

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    Aroch, Itamar; Baneth, Gad; Salant, Harold; Nachum-Biala, Yaarit; Berkowitz, Asaf; Shamir, Merav; Chai, Orit

    2018-06-01

    An 8-year-old mixed-breed dog was presented for acute, progressive weakness and ataxia, inappetence, and weight loss. The patient was mentally normal, but nonambulatory, with a right head tilt, right positional ventral strabismus, and slight head tremors. A neurologic lesion was localized to the cerebellum and right brainstem. Cerebrospinal fluid (CSF) analysis showed a markedly increased protein concentration and mixed pleocytosis, with eosinophil predominance (44%), intracytoplasmic inclusions within eosinophils, consistent with Ehrlichia canis (E canis) morulae, and Toxoplasma gondii (T gondii) or Neospora caninum (N caninum) tachyzoites within eosinophils and monocytes. A serum indirect immunofluorescent antibody test was positive for N caninum (titer 1:12 800) and negative for T gondii. Both blood and CSF PCR results were N caninum- and E canis-positive and T gondii- and Anaplasma phagocytophilum-negative, and blood PCR, but not CSF PCR, was Hepatozoon canis-positive. The dog was treated for 30 days with clindamycin, sulfamethoxazole-trimethoprim, doxycycline, prednisone, and cephalosporin, but did not improve neurologically, and was euthanized. Brain histopathology showed moderate multifocal, subacute meningoencephalitis with necrosis and gliosis. The neurologic disease was mostly attributed to central nervous system (CNS) neosporosis, with the possible contribution of ehrlichiosis, which was likely a manifestation of blood-brain barrier disruption. Hepatozoonosis was probably a result or cause of underlying immunosuppression. To our knowledge, this is the first report of CNSN caninum and E canis co-infection detected by both CSF PCR and cytology and E canis morulae identified within CSF eosinophils. © 2018 American Society for Veterinary Clinical Pathology.

  1. Serology, molecular detection and risk factors of Ehrlichia canis infection in dogs in Costa Rica.

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    Barrantes-González, Alexander V; Jiménez-Rocha, Ana E; Romero-Zuñiga, Juan José; Dolz, Gaby

    2016-10-01

    A cross-sectional study combining different serological and molecular techniques for the detection of Ehrlichia species in dogs and their ticks was carried out with data from all regions of Costa Rica. A seroprevalence of 32.1% (131/408), and infection with E. canis of 3.2% (13/407) was found, whereas 6.9% (9/130) of ticks attached to the dogs were PCR positive to E. canis. Higher prevalences were found outside the Greater Metropolitan Area (GMA). Risk factors associated with E. canis seropositivity were age, between 2 and 7 years (RR: 1.6, 95% CI: 1.2-2.2) and 8-15 years (RR: 1.8, 95% CI: 1.2-3.0), number of dogs/total of households [Dogs per Household Ratio (DHR) ≥3.1 (RR: 2.0; 95% CI: 1.4-3.0)], number of dogs infested with at least one tick/total of dogs sampled [Tick Infestation Prevalence (TIP)≥31% (RR: 2.1; 95% CI:1.3-3.3)] and living outside the GMA (RR: 1.7; 95% CI: 1.2-2.4) and being a mixed-breed dog (RR: 1.5; 95% CI: 1.1-2.1). Risk factors for E. canis PCR positive dogs were a depressive attitude (OR: 11.2; 95% CI: 1.1-115.9), fever (OR:4.8; 95% CI:1.2-19.3), DHR≥3.1 (OR: 5.7; 95% CI:1.7-19.2)], number of ticks/total of dogs sampled [Tick Distribution Ratio (TDR) ≥2.1 (OR: 6.5; 95% CI: 1.3-31.8)], and TIP≥40% (OR: 5.7; 95% CI: 1.7-19.2). This paper describes E. canis seroprevalence, PCR prevalence and tick analysis in dogs from Costa Rica, with associated clinical signs and owner perceptions. In summary, most of the E. canis infections in dogs in our country seemed to pass unnoticed by owners. Since most of the seropositive dogs (97.7%, 131/134) were negative for E. canis DNA in their blood, it is important to determine in future studies if these dogs recovered from the E. canis infection without any medication, or are persistently infected, and will develop chronic disease. Copyright © 2016 Elsevier GmbH. All rights reserved.

  2. Canine infection with Borrelia burgdorferi, Dirofilaria immitis, Anaplasma spp. and Ehrlichia spp. in Canada, 2013-2014.

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    Herrin, Brian H; Peregrine, Andrew S; Goring, Jonas; Beall, Melissa J; Little, Susan E

    2017-05-19

    Canine test results generated by veterinarians throughout Canada from 2013-2014 were evaluated to assess the geographical distribution of canine infection with Borrelia burgdorferi, Dirofilaria immitis, Ehrlichia spp., and Anaplasma spp. The percent positive test results of 115,636 SNAP® 4Dx® Plus tests from dogs tested were collated by province and municipality to determine the distribution of these vector-borne infections in Canada. A total of 2,844/115,636 (2.5%) dogs tested positive for antibody to B. burgdorferi. In contrast, positive test results for D. immitis antigen and antibodies to Ehrlichia spp. and Anaplasma spp. were low, with less than 0.5% of dogs testing positive for any one of these three agents nationwide. Provincial seroprevalence for antibodies to B. burgdorferi ranged from 0.5% (Saskatchewan)-15.7% (Nova Scotia); the areas of highest percent positive test results were in proximity to regions in the USA considered endemic for Lyme borreliosis, including Nova Scotia (15.7%) and Eastern Ontario (5.1%). These high endemic foci, which had significantly higher percent positive test results than the rest of the nation (P Canada. Using dogs as sentinels for these pathogens can aid in recognition of the public and veterinary health threat that each pose.

  3. Infection of Anaplasma phagocytophilum and Ehrlichia spp. in Opossums and Dogs in Campeche, Mexico: The Role of Tick Infestation

    Directory of Open Access Journals (Sweden)

    Edgar Rojero-Vázquez

    2017-12-01

    Full Text Available In recent years, some tick-borne diseases such as anaplasmosis and ehrlichiosis became widespread worldwide, threatening the health of humans, domestic animals and wildlife. The aims of this study were to determine the presence of Anaplasma phagocytophilum, Ehrlichia canis, and Ehrlichia chaffeensis in 102 opossums (Didelphis spp. and 44 owned free-ranging dogs in southeastern Mexico using a specific polymerase chain reaction (PCR. A. phagocytophilum was detected in opossums and dogs with a prevalence of 3 and 27%, respectively. E. canis was only present in 7% of dogs, while we didn't detect E. chaffeensis in any host. We report the first evidence of infections of A. phagocytophilum in Didelphis virginiana and D. marsupialis in Mexico. The infection rates and patterns we found of A. phagocytophilum suggest that dogs are more directly involved in the ecology of this pathogen than opossums. Despite the small prevalence found, our results are of public health concern because of the zoonotic capabilities of A. phagocytophilum, the high tick infestation rates found and because both opossums and free-ranging dogs can achieve high population densities in the region.

  4. Pathology of dogs in Campo Grande, MS, Brazil naturally co-infected with Leishmania infantum and Ehrlichia canis

    Directory of Open Access Journals (Sweden)

    Gisele Braziliano Andrade

    2014-12-01

    Full Text Available Different parasites that commonly occur concomitantly can influence one another, sometimes with unpredictable effects. We evaluated pathological aspects of dogs naturally co-infected with Leishmania infantum and Ehrlichia canis. The health status of the dogs was investigated based on histopathological, hematological and biochemical analyses of 21 animals infected solely with L. infantum and 22 dogs co- infected with L. infantum and E. canis. The skin of both groups showed chronic, predominantly lymphohistioplasmacytic inflammatory reaction. The plasmacytosis in the lymphoid tissues was likely related with the hypergammaglobulinemia detected in all the dogs. The disorganization of extracellular matrix found in the reticular dermis of the inguinal region and ear, characterized by the substitution of thick collagen fibers for thin fibers, was attributed to the degree of inflammatory reaction, irrespective of the presence of parasites. In addition, the histopathological analysis revealed that twice as many dogs in the co-infected group presented Leishmania amastigotes in the ear skin than those infected solely with Leishmania, increasing the possibility of becoming infected through sand fly vectors. Our findings highlight the fact that the health of dogs infected concomitantly with L. infantum and E. canis is severely compromised due to their high levels of total plasma protein, globulins, alkaline phosphatase and creatine kinase, and severe anemia.

  5. Autologous /sup 111/In-oxine-labeled granulocytes in Yersinia infections

    Energy Technology Data Exchange (ETDEWEB)

    Becker, W.; Boerner, W.; Fischbach, W.

    1985-04-01

    Autologous /sup 111/In-oxine-labeled granulocytes have proved to be valuable for the localization of inflammatory bowel diseases, especially Crohn's disease and ulcerative colitis. Other rare inflammatory bowel diseases also yield positive /sup 111/In scans. One case of Yersinia infection of the terminal ileum (Yersinia enterocolitica) showing an accumulation of /sup 111/In-oxine-labeled granulocytes 0.5, 4, and 24 h after the reinjection of the labeled cells is described. The 4-day fecal excretion of /sup 111/In-oxine granulocytes showed a slight inflammatory activity of the terminal ileum. One negative scan is reported in a cotrimoxazole-treated patient with Yersinia infection.

  6. Type 3 Deiodinase Is Highly Expressed in Infiltrating Neutrophilic Granulocytes in Response to Acute Bacterial Infection

    NARCIS (Netherlands)

    Boelen, Anita; Boorsma, Jeffrey; Kwakkel, Joan; Wieland, Catharina W.; Renckens, Rosemarijn; Visser, Theo J.; Fliers, Eric; Wiersinga, Wilmar M.

    2008-01-01

    Background: Macrophages and polymorphonuclear cells (PMNs) play an important role in the first line of defense against bacteria by infiltrating the infected organ in order to clear the harmful pathogen. Our earlier studies showed that granulocytes express type 3 deiodinase (D3) when activated during

  7. Granulocyte colony-stimulating factor protects mice during respiratory virus infections.

    Directory of Open Access Journals (Sweden)

    Tamar Hermesh

    Full Text Available A burst in the production of pro-inflammatory molecules characterizes the beginning of the host response to infection. Cytokines, chemokines, and growth factors work in concert to control pathogen replication and activate innate and adaptive immune responses. Granulocyte colony-stimulating factor (G-CSF mobilizes and activates hematopoietic cells from the bone marrow, and it has been shown to mediate the generation of effective immunity against bacterial and fungal infections. G-CSF is produced at high levels in the lungs during infection with influenza and parainfluenza viruses, but its role during these infections is unknown. Here we show that during infection of mice with a non-lethal dose of influenza or Sendai virus, G-CSF promotes the accumulation of activated Ly6G+ granulocytes that control the extent of the lung pro-inflammatory response. Remarkably, these G-CSF-mediated effects facilitate viral clearance and sustain mouse survival.

  8. Comparative Experimental Infection Study in Dogs with Ehrlichia canis, E. chaffeensis, Anaplasma platys and A. phagocytophilum.

    Science.gov (United States)

    Nair, Arathy D S; Cheng, Chuanmin; Ganta, Chanran K; Sanderson, Michael W; Alleman, Arthur R; Munderloh, Ulrike G; Ganta, Roman R

    2016-01-01

    Dogs acquire infections with the Anaplasmataceae family pathogens, E. canis, E. chaffeensis, E. ewingii, A. platys and A. phagocytophilum mostly during summer months when ticks are actively feeding on animals. These pathogens are also identified as causing diseases in people. Despite the long history of tick-borne diseases in dogs, much remains to be defined pertaining to the clinical and pathological outcomes of infections with these pathogens. In the current study, we performed experimental infections in dogs with E. canis, E. chaffeensis, A. platys and A. phagocytophilum. Animals were monitored for 42 days to evaluate infection-specific clinical, hematological and pathological differences. All four pathogens caused systemic persistent infections detectible throughout the 6 weeks of infection assessment. Fever was frequently detected in animals infected with E. canis, E. chaffeensis, and A. platys, but not in dogs infected with A. phagocytophilum. Hematological differences were evident in all four infected groups, although significant overlap existed between the groups. A marked reduction in packed cell volume that correlated with reduced erythrocytes and hemoglobin was observed only in E. canis infected animals. A decline in platelet numbers was common with E. canis, A. platys and A. phagocytophilum infections. Histopathological lesions in lung, liver and spleen were observed in all four groups of infected dogs; infection with E. canis had the highest pathological scores, followed by E. chaffeensis, then A. platys and A. phagocytophilum. All four pathogens induced IgG responses starting on day 7 post infection, which was predominantly comprised of IgG2 subclass antibodies. This is the first detailed investigation comparing the infection progression and host responses in dogs after inoculation with four pathogens belonging to the Anaplasmataceae family. The study revealed a significant overlap in clinical, hematological and pathological changes resulting from the

  9. Identificación morfológica de Ehrlichia sp. en las plaquetas de pacientes con infección por virus de la inmunodeficiencia humana, en Venezuela Morphologic identification of Ehrlichia sp. in the platelets of patients infected with the human immunodeficiency virus in Venezuela

    Directory of Open Access Journals (Sweden)

    Irene del Carmen de Tamí

    2004-11-01

    Full Text Available OBJETIVO: Determinar la frecuencia de infección por bacterias del género Ehrlichia en una población de pacientes con infección por virus de la inmunodeficiencia humana (VIH. Como se sabe, la infección por VIH suele culminar en el síndrome de inmunodeficiencia adquirida (SIDA después de un período variable en que la persona queda expuesta a distintos tipos de infecciones oportunistas, cuya gravedad varía según el deterioro de su sistema inmunitario. La ehrliquiosis humana es una enfermedad infecciosa de reconocimiento reciente que se transmite por garrapatas y que es causada por especies de Ehrlichia. Se trata de microorganismos gramnegativos, intracelulares obligados, que muestran tropismo por células sanguíneas (leucocitos y plaquetas. En Venezuela se identificó por primera vez en seres humanos en 1994, con la detección de microcolonias (mórulas en el citoplasma de plaquetas. MATERIAL Y MÉTODOS: Para el estudio se reunieron muestras de sangre periférica de 87 pacientes con seropositividad a VIH recibidos en el Laboratorio de Inmunología del Instituto de Oncología y Hematología, en Caracas, Venezuela, que es uno de los centros de referencia nacionales para casos de infección por VIH. Se revisaron retrospectivamente, al microscopio óptico, frotis elaborados con capa blanca sanguínea concentrada, teñidos con colorante de Wright y sellados con resina para su conservación. RESULTADO: Se identificó Ehrlichia trombocítica en 12 de los 87 sujetos del estudio, es decir, en 13,8%. CONCLUSIÓN: La identificación de Ehrlichia trombocítica en pacientes seropositivos sugiere la necesidad de tener en cuenta la ehrliquiosis como posible diagnóstico en la población con infección por VIH.OBJECTIVE: To determine the frequency of infection by bacteria of the genus Ehrlichia in a population of patients infected with the human immunodeficiency virus (HIV. As is widely recognized, HIV infection is usually followed by the acquired

  10. Indium-111 labeled purified granulocytes in the diagnosis of synthetic vascular graft infection

    International Nuclear Information System (INIS)

    Forstrom, L.A.; Dewanjee, M.K.; Chowdhury, S.; Brown, M.L.

    1988-01-01

    Indium-111 labeled leukocytes have been shown to be useful in the diagnosis of synthetic vascular graft infection. To minimize the potential effects of labeled red blood cells and platelets on image interpretation, the authors prepared purified autologous granulocytes (PG) from 84 ml of blood using Volex enhanced gravity sedimentation and Ficoll-Hypaque double density centrifugation. The labeling efficiency of PG with In-111 tropolone was 90 +/- 9% (mean +/- SD). Imaging was performed 18-24 hours following injection of approximately 445 microcuries of In-111 PG in 26 patients with suspected infection of vascular grafts that had been implanted 12 days to 12 years prior to the study. In ten patients with proven graft infection, seven had positive In-111 PG scans. Ten of 11 patients without infection had negative scans. In five patients with clinically equivocal findings, scan results were positive in one, negative in one, and equivocal in three. A false-positive scan occurred in a patient with an uninfected inflammatory pseudoaneurysm of an aortic graft. These results confirm an earlier report that In-111 PG imaging is a useful technique in the diagnosis of synthetic vascular graft infection

  11. The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, T U; Aladdin, H

    2000-01-01

    This randomized, placebo-controlled trial examine the long-term effect of granulocyte colony-stimulating factor (G-CSF) on absolute numbers of CD34+ progenitor cells and progenitor cell function in human immunodeficiency virus (HIV)-infected patients. G-CSF (300 microg filgrastim) or placebo was ...

  12. Critical analysis of vector-borne infections in dogs: Babesia vogeli, Babesia gibsoni, Ehrlichia canis and Hepatozoon canis in Punjab, India.

    Science.gov (United States)

    Singla, Lachhman Das; Sumbria, Deepak; Mandhotra, Ajay; Bal, M S; Kaur, Paramjit

    2016-12-01

    There are few published studies on various vector borne diseases of dogs in India and most depict clinical infection in dogs, diagnosed by observation of the haemopathogens in stained blood smears. This study provides the first report regarding molecular confirmation and ancestral relationship analysis of blood smears positive cases of assorted haemopathogens in Punjab province of India. On blood smear examination, haemopathogens were observed in 124 out of 778 (15.95%, 95% CI: 13.53- 18.68) blood smears. Further polymerase chain reactions (PCR) was used on bloods smear positive cases to validate the results. Out of 778 blood samples, Babesia gibsoni was most common parasite infecting dogs (15.04%, 95% CI: 12.7-17.72), followed by Ehrlichia canis (0.39%, 95% CI: 0.0-1.13), infection of Babesia vogeli and Hepatozoon canis was same (0.26%, 95% CI: 0.0-0.9). Among various risk factors studied (age, sex, season), prevalence of infection was non-significantly higher in 1-2 year of age group (19.88%, 95% CI: 14.45-26.71), regarding sex same prevalence was recorded (15.94%), and chances of infection was highest in pre-monsoon i.e. summer (18.26%, 95% CI: 14.49-22.76). Phylogenetic analysis revealed ancestral background of Ludhiana isolates of B. vogeli, B. gibsoni, H. canis, and E. canis with the isolates of Philippines, Mongolia and Tunisia.

  13. Hematologic improvement in dogs with parvovirus infection treated with recombinant canine granulocyte-colony stimulating factor.

    Science.gov (United States)

    Duffy, A; Dow, S; Ogilvie, G; Rao, S; Hackett, T

    2010-08-01

    Previously, dogs with canine parvovirus-induced neutropenia have not responded to treatment with recombinant human granulocyte-colony stimulating factor (rhG-CSF). However, recombinant canine G-CSF (rcG-CSF) has not been previously evaluated for treatment of parvovirus-induced neutropenia in dogs. We assessed the effectiveness of rcG-CSF in dogs with parvovirus-induced neutropenia with a prospective, open-label, nonrandomized clinical trial. Endpoints of our study were time to recovery of WBC and neutrophil counts, and duration of hospitalization. 28 dogs with parvovirus and neutropenia were treated with rcG-CSF and outcomes were compared to those of 34 dogs with parvovirus and neutropenia not treated with rcG-CSF. We found that mean WBC and neutrophil counts were significantly higher (P parvovirus infection, but indicate the need for additional studies to evaluate overall safety of the treatment.

  14. Citrate synthase gene sequence: a new tool for phylogenetic analysis and identification of Ehrlichia.

    Science.gov (United States)

    Inokuma, H; Brouqui, P; Drancourt, M; Raoult, D

    2001-09-01

    The sequence of the citrate synthase gene (gltA) of 13 ehrlichial species (Ehrlichia chaffeensis, Ehrlichia canis, Ehrlichia muris, an Ehrlichia species recently detected from Ixodes ovatus, Cowdria ruminantium, Ehrlichia phagocytophila, Ehrlichia equi, the human granulocytic ehrlichiosis [HGE] agent, Anaplasma marginale, Anaplasma centrale, Ehrlichia sennetsu, Ehrlichia risticii, and Neorickettsia helminthoeca) have been determined by degenerate PCR and the Genome Walker method. The ehrlichial gltA genes are 1,197 bp (E. sennetsu and E. risticii) to 1,254 bp (A. marginale and A. centrale) long, and GC contents of the gene vary from 30.5% (Ehrlichia sp. detected from I. ovatus) to 51.0% (A. centrale). The percent identities of the gltA nucleotide sequences among ehrlichial species were 49.7% (E. risticii versus A. centrale) to 99.8% (HGE agent versus E. equi). The percent identities of deduced amino acid sequences were 44.4% (E. sennetsu versus E. muris) to 99.5% (HGE agent versus E. equi), whereas the homology range of 16S rRNA genes was 83.5% (E. risticii versus the Ehrlichia sp. detected from I. ovatus) to 99.9% (HGE agent, E. equi, and E. phagocytophila). The architecture of the phylogenetic trees constructed by gltA nucleotide sequences or amino acid sequences was similar to that derived from the 16S rRNA gene sequences but showed more-significant bootstrap values. Based upon the alignment analysis of the ehrlichial gltA sequences, two sets of primers were designed to amplify tick-borne Ehrlichia and Neorickettsia genogroup Ehrlichia (N. helminthoeca, E. sennetsu, and E. risticii), respectively. Tick-borne Ehrlichia species were specifically identified by restriction fragment length polymorphism (RFLP) patterns of AcsI and XhoI with the exception of E. muris and the very closely related ehrlichia derived from I. ovatus for which sequence analysis of the PCR product is needed. Similarly, Neorickettsia genogroup Ehrlichia species were specifically identified by

  15. Ehrlichia chaffeensis infection in the reservoir host (white-tailed deer and in an incidental host (dog is impacted by its prior growth in macrophage and tick cell environments.

    Directory of Open Access Journals (Sweden)

    Arathy D S Nair

    Full Text Available Ehrlichia chaffeensis, transmitted from Amblyomma americanum ticks, causes human monocytic ehrlichiosis. It also infects white-tailed deer, dogs and several other vertebrates. Deer are its reservoir hosts, while humans and dogs are incidental hosts. E. chaffeensis protein expression is influenced by its growth in macrophages and tick cells. We report here infection progression in deer or dogs infected intravenously with macrophage- or tick cell-grown E. chaffeensis or by tick transmission in deer. Deer and dogs developed mild fever and persistent rickettsemia; the infection was detected more frequently in the blood of infected animals with macrophage inoculum compared to tick cell inoculum or tick transmission. Tick cell inoculum and tick transmission caused a drop in tick infection acquisition rates compared to infection rates in ticks fed on deer receiving macrophage inoculum. Independent of deer or dogs, IgG antibody response was higher in animals receiving macrophage inoculum against macrophage-derived Ehrlichia antigens, while it was significantly lower in the same animals against tick cell-derived Ehrlichia antigens. Deer infected with tick cell inoculum and tick transmission caused a higher antibody response to tick cell cultured bacterial antigens compared to the antibody response for macrophage cultured antigens for the same animals. The data demonstrate that the host cell-specific E. chaffeensis protein expression influences rickettsemia in a host and its acquisition by ticks. The data also reveal that tick cell-derived inoculum is similar to tick transmission with reduced rickettsemia, IgG response and tick acquisition of E. chaffeensis.

  16. Serologic Evidence of Human Monocytic and Granulocytic Ehrlichiosis in Israel

    Science.gov (United States)

    Keysary, Avi; Amram, Lili; Keren, Gershon; Sthoeger, Zev; Potasman, Israel; Jacob, Amir; Strenger, Carmella; Dawson, Jacqueline E.

    1999-01-01

    We conducted a retrospective serosurvey of 1,000 persons in Israel who had fever of undetermined cause to look for Ehrlichia chaffeensis antibodies. Four of five cases with antibodies reactive to E. chaffeensis were diagnosed in the summer, when ticks are more active. All patients had influenzalike symptoms with high fever. None of the cases was fatal. Three serum samples were also seroreactive for antibodies to E. canis, and one was also reactive to the human granulocytic ehrlichiosis (HGE) agent. The titer to the HGE agent in this patient was higher than the serum titer to E. chaffeensis, and the Western blot analysis also indicated that the HGE agent was the primary cause of infection. We present the first serologic evidence that the agents of human monocytic ehrlichiosis (HME) and HGE are present in Israel. Therefore, human ehrlichiosis should be included in the differential diagnoses for persons in Israel who have been exposed to ticks and have influenzalike symptoms. PMID:10603210

  17. CD64 on monocytes and granulocytes in severe acute bronchiolitis: Pilot study on its usefulness as a bacterial infection biomarker.

    Science.gov (United States)

    García-Salido, Alberto; Serrano-González, Ana; Casado-Flores, Juan; Sierra-Colomina, Montserrat; de Azagra-Garde, Amelia Martínez; García-Teresa, María Ángeles; Melen, Gustavo J; Ramírez-Orellana, Manuel

    2018-02-27

    The CD64 receptor has been described as a biomarker of bacterial infection. We speculated that CD64 surface expression on monocytes and granulocytes of children with severe acute bronchiolitis (SAB) could be altered in cases of probable bacterial infection (PBI) determined using classical biomarkers (procalcitonin and C-reactive protein, leukocyte count, and radiographic findings). A prospective observational pilot study was conducted from October 2015 to February 2016 in children admitted for pediatric critical care. A blood sample was taken in the first 24 hours of admission, and CD64 was measured by flow cytometry. The values obtained were analyzed and correlated with traditional biomarkers of PBI. Thirty-two children were included; a correlation was found between CD64 expression and the PBI criteria. CD64 surface expression was higher in children with PBI (area under the receiver operating characteristic curve of 0.73; P = 0.042) and the percentage of CD64 + granulocytes was higher in children with PBI. This is the first study to describe CD64 surface expression on monocytes and granulocytes in SAB, finding CD64 values to be higher in children with PBI. Larger clinical studies are needed to elucidate the real accuracy of CD64 as a biomarker of bacterial infection. ©2018 Society for Leukocyte Biology.

  18. Comparative strain analysis of Anaplasma phagocytophilum infection and clinical outcomes in a canine model of granulocytic anaplasmosis.

    Science.gov (United States)

    Scorpio, Diana G; Dumler, J Stephen; Barat, Nicole C; Cook, Judith A; Barat, Christopher E; Stillman, Brett A; DeBisceglie, Kristen C; Beall, Melissa J; Chandrashekar, Ramaswamy

    2011-03-01

    A pilot study was conducted to determine whether existing human or canine strains of Anaplasma phagocytophilum would reproduce clinical disease in experimentally inoculated dogs similar to dogs with naturally acquired granulocytic anaplasmosis. Six hounds were inoculated intravenously with one human and two canine strains of A. phagocytophilum that were propagated in vitro in HL-60 cells or in infected autologous neutrophils. Infected dogs were monitored for lethargy, anorexia, petechiae, lymphadenopathy, and fever. Dogs were assessed for complete blood count (CBC), serum chemistry, and serology (IFA and SNAP® 4Dx®); for A. phagocytophilum blood load by quantitative polymerase chain reaction; and for cytokine production. Prominent clinical signs were generalized lymphadenopathy and scleral injection; only one dog developed fever lasting 4 days. Notable laboratory alterations included sustained leukopenia and thrombocytopenia in all dogs. A. phagocytophilum morulae were noted in blood between days 10 and 11, although all dogs retained A. phagocytophilum DNA in blood through day 60. All dogs seroconverted by days 10-15 by IFA, and by days 17-30 by SNAP 4Dx; cytokine analyses revealed 10-fold increases in interleukin-2 and interleukin-18 in the neutrophil-propagated 98E4 strain-infected dog. All A. phagocytophilum strains produced infection, although canine 98E4 strain reproduced clinical signs, hematologic changes, and inflammatory cytokine elevations most consistent with granulocytic anaplasmosis when recognized clinically. Therefore, this strain should be considered for use in future studies of A. phagocytophilum canine infection models.

  19. Early Expansion of Circulating Granulocytic Myeloid-derived Suppressor Cells Predicts Development of Nosocomial Infections in Patients with Sepsis.

    Science.gov (United States)

    Uhel, Fabrice; Azzaoui, Imane; Grégoire, Murielle; Pangault, Céline; Dulong, Joelle; Tadié, Jean-Marc; Gacouin, Arnaud; Camus, Christophe; Cynober, Luc; Fest, Thierry; Le Tulzo, Yves; Roussel, Mikael; Tarte, Karin

    2017-08-01

    Sepsis induces a sustained immune dysfunction responsible for poor outcome and nosocomial infections. Myeloid-derived suppressor cells (MDSCs) described in cancer and inflammatory processes may be involved in sepsis-induced immune suppression, but their clinical impact remains poorly defined. To clarify phenotype, suppressive activity, origin, and clinical impact of MDSCs in patients with sepsis. Peripheral blood transcriptomic analysis was performed on 29 patients with sepsis and 15 healthy donors. A second cohort of 94 consecutive patients with sepsis, 11 severity-matched intensive care patients, and 67 healthy donors was prospectively enrolled for flow cytometry and functional experiments. Genes involved in MDSC suppressive functions, including S100A12, S100A9, MMP8, and ARG1, were up-regulated in the peripheral blood of patients with sepsis. CD14 pos HLA-DR low/neg monocytic (M)-MDSCs were expanded in intensive care unit patients with and without sepsis and CD14 neg CD15 pos low-density granulocytes/granulocytic (G)-MDSCs were more specifically expanded in patients with sepsis (P sepsis. G-MDSCs, made of immature and mature granulocytes expressing high levels of degranulation markers, were specifically responsible for arginase 1 activity. High initial levels of G-MDSCs, arginase 1, and S100A12 but not M-MDSCs were associated with subsequent occurrence of nosocomial infections. M-MDSCs and G-MDSCs strongly contribute to T-cell dysfunction in patients with sepsis. More specifically, G-MDSCs producing arginase 1 are associated with a higher incidence of nosocomial infections and seem to be major actors of sepsis-induced immune suppression.

  20. Hacker Within! Ehrlichia chaffeensis Effector Driven Phagocyte Reprogramming Strategy

    Directory of Open Access Journals (Sweden)

    Taslima Taher Lina

    2016-05-01

    Full Text Available Ehrlichia chaffeensis is a small, gram negative, obligately intracellular bacterium that preferentially infects mononuclear phagocytes. It is the etiologic agent of human monocytotropic ehrlichiosis (HME, an emerging life-threatening tick-borne zoonosis. Mechanisms by which E. chaffeensis establishes intracellular infection, and avoids host defenses are not well understood, but involve functionally relevant host-pathogen interactions associated with tandem and ankyrin repeat effector proteins. In this review, we discuss the recent advances in our understanding of the molecular and cellular mechanisms that underlie Ehrlichia host cellular reprogramming strategies that enable intracellular survival.

  1. Aspectos epidemiológicos, clínicos e hematológicos de 251 cães portadores de mórula de Ehrlichia spp. naturalmente infectados Epidemiological, clinical, and hematological aspects of 251 dogs naturally infected with Ehrlichia spp. morulae

    Directory of Open Access Journals (Sweden)

    S. Borin

    2009-06-01

    Full Text Available Realizou-se um estudo retrospectivo dos aspectos epidemiológicos, sinais clínicos, dados de exame físico e alterações hematológicas da erliquiose em 251 cães naturalmente infectados por Ehrlichia spp. Dos 4407 casos atendidos em hospital veterinário no período de janeiro de 2002 a dezembro de 2003, verificou-se que 251 cães eram portadores de mórula de Ehrlichia spp. em leucócitos de sangue periférico. Destes, 48 foram eliminados das avaliações por apresentarem patologias concomitantes. Nos 203 cães restantes, verificou-se que houve maior ocorrência em fêmeas (61,1% e que a doença manteve-se constante durante todo o período avaliado. Observou-se que 38% encontravam-se na faixa etária entre um e 23 meses e 58,6% eram de raça definida. As principais alterações clínicas observadas foram apatia, anorexia/hiporexia, vômito, secreção oculonasal e esplenomegalia. Cento e cinco cães apresentaram temperatura retal entre 38 e 39,5°C. As alterações observadas com maior frequência no hemograma foram anemia, predominando o tipo normocítica normocrômica (58,2%; desvio nuclear de neutrófilos para a esquerda (67% e eosinopenia (58,1%.A study of epidemiological and clinical aspects, alterations of physical exams, and hematological changes of canine ehrlichiosis was performed. A retrospective study was performed in 4,407 dogs referred to a Veterinary Hospital from January 2002 to December 2003. Of all cases, 251 dogs showed Ehrlichia spp. morulae. Among these, 48 were excluded from the study due to other co-infection by other pathologies. In the other 203 evaluated dogs, females (61.1% were more infected than males. The dogs aged from one to 23 months (68.6% and 58.6% were definite breed. Emesis, apathy, anorexia/hypoxeria, spleenomegaly, and nasal discharge were the most common signs presented. Rectal temperature was 38 - 39.5ÚC in 105 dogs. The most usual changes seen during the hematological tests were normochromic and

  2. Serological survey of Borrelia burgdorferi sensu lato, Anaplasma phagocytophilum, and Ehrlichia canis infections in rural and urban dogs in Central Italy

    Directory of Open Access Journals (Sweden)

    Valentina Virginia Ebani

    2014-11-01

    Full Text Available [b]Introduction[i][/i][/b][i]. Borrelia burgdorferi [/i]sensu lato (s.l. and Anaplasma phagocytophilum are well known zoonotic pathogens, whereas[i] Ehrlichia canis[/i] is usually considered to be of veterinary concern, although on the basis of recent reports it also seems to be able to infect humans. [b]objective[/b]. The aim of the study was to determine the seroprevalence of [i]B. burgdorferi [/i]s.l., A. phagocytophilum and [i]E. canis[/i] in an Italian canine population, and to verify if there are differences between dogs living in urban areas and those from a rural environment. [b]materials and method.[/b] Blood sera of 1,965 dogs, 1,235 from cities and 730 from rural areas, were tested by indirect immunofluorescent assay (IFAT. [b]results[/b]. The overall seroprevalence was highest for E. canis (7.07%, followed by [i]A. phagocytophilum[/i] (4.68%, and [i]B. burgdorferi[/i] s.l. (1.47%. Rural dogs showed the highest seroprevalence to [i]B. burgdorferi[/i] s.l. and [i]A. phagocytophilum[/i]. No significant differences were observed between rural and urban [i]E. canis[/i]-positive dogs. A low percentage (1.32% of dogs with dual seropositivity was detected, and no triple positive reactions were observed. No significant differences were detected in the seroprevalence of the three agents in relationship to the age and gender of the dogs. Seroprevalence in the five years considered were not statistically different, except for the lowest rate for [i]E. canis[/i] observed in 2012. [b]conclusions[/b]. The results confirm the presence of [i]B. burgdorferi[/i] s.l., [i]A. phagocytophilum[/i] and [i]E. canis[/i] in Italian dogs in both urban and rural areas. Monitoring pet dogs, which share the same environment with their owners, is useful for identifying the presence of tick-borne disease agents of both veterinary and public health significance

  3. Septal endocarditis, bone infection and severe leg ischemia detected in Tc-99m labelled monoclonal anti granulocyte scan

    International Nuclear Information System (INIS)

    Bechelaghem, A.I; Habbeche, M; Benlabgaa, R; Ghedbane, IE; Hanzal, A; Khelifa, A; Mechcken, F; Bourezak, SE; Bouyoucef, SE

    2006-01-01

    Patient 28 years old has continued to have a persistent fever (39.2 O C), despite ten days treatment by specific antibiotics for bacterial endocarditis associated to a recent claudication of the right lower leg. The persistent fever has motivated a 99mTc-labelled monoclonal anti granulocyte scan which has showed an important uptake in the myocardial septum, and other infection locations in temporal bone and in right tibial arteries. Two days after, a nanocolloids-99mTc WBS showed no uptake in the heart area, a total absence of uptake of the nanocolloids in the bone marrow of right tibia b and cranial SPECT views confirmed the infectious site in the right temporal bone. New antibiotic strategy was adopted successfully associated with surgical amputation of the right lower leg (au)

  4. Granulocyte kinetics

    International Nuclear Information System (INIS)

    Peters, A.M.; Lavender, J.P.; Saverymuttu, S.H.

    1985-01-01

    By using density gradient materials enriched with autologous plasma, the authors have been able to isolate granulocutes from other cellular elements and label them with In-111 without separation from a plasma environment. The kinetic behavior of these cells suggests that phenomena attributed to granulocyte activation are greatly reduced by this labeling. Here, they review their study of granulocyte kinetics in health and disease in hope of quantifying sites of margination and identifying principal sites of destruction. The three principle headings of the paper are distribution, life-span, and destruction

  5. Giardia duodenalis infection reduces granulocyte infiltration in an in vivo model of bacterial toxin-induced colitis and attenuates inflammation in human intestinal tissue.

    Directory of Open Access Journals (Sweden)

    James A Cotton

    Full Text Available Giardia duodenalis (syn. G. intestinalis, G. lamblia is a predominant cause of waterborne diarrheal disease that may lead to post-infectious functional gastrointestinal disorders. Although Giardia-infected individuals could carry as much as 106 trophozoites per centimetre of gut, their intestinal mucosa is devoid of overt signs of inflammation. Recent studies have shown that in endemic countries where bacterial infectious diseases are common, Giardia infections can protect against the development of diarrheal disease and fever. Conversely, separate observations have indicated Giardia infections may enhance the severity of diarrheal disease from a co-infecting pathogen. Polymorphonuclear leukocytes or neutrophils (PMNs are granulocytic, innate immune cells characteristic of acute intestinal inflammatory responses against bacterial pathogens that contribute to the development of diarrheal disease following recruitment into intestinal tissues. Giardia cathepsin B cysteine proteases have been shown to attenuate PMN chemotaxis towards IL-8/CXCL8, suggesting Giardia targets PMN accumulation. However, the ability of Giardia infections to attenuate PMN accumulation in vivo and how in turn this effect may alter the host inflammatory response in the intestine has yet to be demonstrated. Herein, we report that Giardia infection attenuates granulocyte tissue infiltration induced by intra-rectal instillation of Clostridium difficile toxin A and B in an isolate-dependent manner. This attenuation of granulocyte infiltration into colonic tissues paralled decreased expression of several cytokines associated with the recruitment of PMNs. Giardia trophozoite isolates that attenuated granulocyte infiltration in vivo also decreased protein expression of cytokines released from inflamed mucosal biopsy tissues collected from patients with active Crohn's disease, including several cytokines associated with PMN recruitment. These results demonstrate for the first time

  6. Granulocytic sarcoma.

    Science.gov (United States)

    Hutchison, R E; Kurec, A S; Davey, F R

    1990-12-01

    Granulocytic sarcoma is a variant presentation of acute myeloblastic leukemia, occurring in extramedullary locations. It is uncommon, but it may occur at any site and at any age, which necessitates its inclusion in the differential diagnosis of all undifferentiated tumors. Histology, touch-imprint cytology, cytochemistry, immunocytochemistry, electron microscopy, and molecular studies all contribute to the diagnosis.

  7. PREVALENCE OF BABESIA SPP., EHRLICHIA SPP., AND TICK INFESTATIONS IN OKLAHOMA BLACK BEARS (URSUS AMERICANUS).

    Science.gov (United States)

    Skinner, Delaina; Mitcham, Jessica R; Starkey, Lindsay A; Noden, Bruce H; Fairbanks, W Sue; Little, Susan E

    2017-10-01

    American black bears (Ursus americanus) are commonly infested with ticks throughout their range, but there are few surveys for tick-borne disease agents in bears. To characterize tick infestations and determine the prevalence of current infection with Babesia spp. and past or current infection with Ehrlichia spp. in newly re-established populations of black bears in east central and southeastern Oklahoma, US, we identified adult (n=1,048) and immature (n=107) ticks recovered from bears (n=62). We evaluated serum and whole blood samples from a subset (n=49) for antibodies reactive to, and characteristic DNA fragments of, Ehrlichia spp., as well as characteristic DNA fragments of Babesia spp. Amblyomma americanum, the most common tick identified, was found on a majority (56/62; 90%) of bears and accounted for 697/1,048 (66.5%) of all ticks recovered. Other ticks included Dermacentor variabilis (338/1,048; 32.3%) from 36 bears, Amblyomma maculatum (9/1,048; 0.9%) from three bears, and Ixodes scapularis (4/1,048; 0.4%) from three bears. Antibodies reactive to Ehrlichia spp. were detected in every bear tested (49/49; 100%); maximum inverse titers to Ehrlichia chaffeensis ranged from 64-4,096 (geometric mean titer 1,525). However, PCR failed to identify active infection with E. chaffeensis, Ehrlichia ewingii, or an Ehrlichia ruminantium-like agent. Infection with Babesia spp. was detected by PCR in 3/49 (6%) bears. Together these data confirm that tick infestations and infection with tick-borne disease agents are common in bears in the southern US. The significance of these infestations and infections to the health of bears, if any, and the identity of the Ehrlichia spp. responsible for the antibody reactivity seen, warrant further evaluation.

  8. Role of Granulocyte-Macrophage Colony-Stimulating Factor Production by T Cells during Mycobacterium tuberculosis Infection.

    Science.gov (United States)

    Rothchild, Alissa C; Stowell, Britni; Goyal, Girija; Nunes-Alves, Cláudio; Yang, Qianting; Papavinasasundaram, Kadamba; Sassetti, Christopher M; Dranoff, Glenn; Chen, Xinchun; Lee, Jinhee; Behar, Samuel M

    2017-10-24

    Mice deficient for granulocyte-macrophage colony-stimulating factor (GM-CSF -/- ) are highly susceptible to infection with Mycobacterium tuberculosis , and clinical data have shown that anti-GM-CSF neutralizing antibodies can lead to increased susceptibility to tuberculosis in otherwise healthy people. GM-CSF activates human and murine macrophages to inhibit intracellular M. tuberculosis growth. We have previously shown that GM-CSF produced by iNKT cells inhibits growth of M. tuberculosis However, the more general role of T cell-derived GM-CSF during infection has not been defined and how GM-CSF activates macrophages to inhibit bacterial growth is unknown. Here we demonstrate that, in addition to nonconventional T cells, conventional T cells also produce GM-CSF during M. tuberculosis infection. Early during infection, nonconventional iNKT cells and γδ T cells are the main source of GM-CSF, a role subsequently assumed by conventional CD4 + T cells as the infection progresses. M. tuberculosis -specific T cells producing GM-CSF are also detected in the peripheral blood of infected people. Under conditions where nonhematopoietic production of GM-CSF is deficient, T cell production of GM-CSF is protective and required for control of M. tuberculosis infection. However, GM-CSF is not required for T cell-mediated protection in settings where GM-CSF is produced by other cell types. Finally, using an in vitro macrophage infection model, we demonstrate that GM-CSF inhibition of M. tuberculosis growth requires the expression of peroxisome proliferator-activated receptor gamma (PPARγ). Thus, we identified GM-CSF production as a novel T cell effector function. These findings suggest that a strategy augmenting T cell production of GM-CSF could enhance host resistance against M. tuberculosis IMPORTANCE Mycobacterium tuberculosis is the bacterium that causes tuberculosis, the leading cause of death by any infection worldwide. T cells are critical components of the immune

  9. Bone infection in patients suspected of complicating osteomyelitis: the diagnostic value of dual isotope bone-granulocyte scintigraphy

    DEFF Research Database (Denmark)

    Buhl, Thora; Stentzer, Kim; Hede, Adam

    2005-01-01

    : Simultaneous dual isotope bone-granulocyte scintigraphic images were obtained in 42 consecutive patients in whom conventional X-ray, erythrocyte sedimentation rate, and C-reactive protein were also available. 99mTc MDP bone and 111In labelled granulocyte imaging was obtained simultaneously. The images were...... interpreted as positive for osteomyelitis if regions of interests of pathologic 111In granulocyte accumulation included 99mTc MDP activity on the bone images (except in the spine). RESULTS: The sensitivity, specificity, and accuracy were 84, 71 and 79%, respectively, for simultaneous, dual isotope bone......AIM: The purpose of this study was to evaluate the diagnostic value of dual isotope bone-granulocyte scintigraphy in patients with known bone pathology clinically suspected of osteomyelitis, i.e. complicating osteomyelitis, using per-operative bacterial culture from bone as reference. METHODS...

  10. Thermal injury induces impaired function in polymorphonuclear neutrophil granulocytes and reduced control of burn wound infection

    DEFF Research Database (Denmark)

    Calum, H.; Moser, C.; Jensen, P. O.

    2009-01-01

    Severe thermal injury induces immunosuppression, involving all parts of the immune system, especially when large fractions of the total body surface area are affected. An animal model was established to characterize the burn-induced immunosuppression. In our novel mouse model a 6% third-degree burn...... injury was induced in mice with a hot-air blower. The third-degree burn was confirmed histologically. The mice were allocated into five groups: control, shave, burn, infection and burn infection group. At 48 h, a decline in the concentration of peripheral blood leucocytes was observed in the group...... of mice with burn wound. The reduction was ascribed to the decline in concentration of polymorphonuclear neutrophil leucocytes and monocytes. When infecting the skin with Pseudomonas aeruginosa, a dissemination of bacteria was observed only in the burn wound group. Histological characterization...

  11. Radioimmunoimaging of subacute infective endocarditis using a technetium-99m monoclonal granulocyte-specific antibody

    Energy Technology Data Exchange (ETDEWEB)

    Munz, D L; Sandrock, D; Emrich, D [Goettingen Univ. (Germany). Abt. fuer Nuklearmedizin; Morguet, A J; Heim, A; Sold, G; Figulla, H R; Kreuzer, H [Goettingen Univ. (Germany). Abt. fuer Kardiologie und Pulmonologie

    1991-12-01

    Immunoscintigraphy with a technetium-99m murine monoclonal IgG{sub 1} antibody directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen was performed with 20 patients with suspected subacute infective endocarditis (SIE) and 6 controls with suspected inflammatory/infectious disease elsewhere in the body. Immunoscintigraphy and echocardiography localised SIE in 11 of 15 patients in whom the disease could be confirmed. In 4 patients with validated SIE, the immunoscan was abnormal, and the echocardiogram was normal. In another 4 patients, the result was exactly the opposite. These findings suggest that the combination of immunoscintigraphy and echocardiography improves diagnostic efficacy in patients with suspected SIE. (orig.).

  12. Radioimmunoimaging of subacute infective endocarditis using a technetium-99m monoclonal granulocyte-specific antibody

    International Nuclear Information System (INIS)

    Munz, D.L.; Sandrock, D.; Emrich, D.; Morguet, A.J.; Heim, A.; Sold, G.; Figulla, H.R.; Kreuzer, H.

    1991-01-01

    Immunoscintigraphy with a technetium-99m murine monoclonal IgG 1 antibody directed against non-specific cross-reacting antigen (NCA-95) and carcinoembryonic antigen was performed with 20 patients with suspected subacute infective endocarditis (SIE) and 6 controls with suspected inflammatory/infectious disease elsewhere in the body. Immunoscintigraphy and echocardiography localised SIE in 11 of 15 patients in whom the disease could be confirmed. In 4 patients with validated SIE, the immunoscan was abnormal, and the echocardiogram was normal. In another 4 patients, the result was exactly the opposite. These findings suggest that the combination of immunoscintigraphy and echocardiography improves diagnostic efficacy in patients with suspected SIE. (orig.)

  13. Extracellular Trap Formation in Response to Trypanosoma cruzi Infection in Granulocytes Isolated From Dogs and Common Opossums, Natural Reservoir Hosts

    Directory of Open Access Journals (Sweden)

    Nicole de Buhr

    2018-05-01

    Full Text Available Granulocytes mediate the first line of defense against infectious diseases in humans as well as animals and they are well known as multitasking cells. They can mediate antimicrobial activity by different strategies depending on the pathogen they encounter. Besides phagocytosis, a key strategy against extracellular pathogens is the formation of extracellular traps (ETs. Those ETs mainly consist of DNA decorated with antimicrobial components and mediate entrapment of various pathogens. In the last years, various studies described ET formation as response to bacteria, viruses and parasites e.g., Trypanosma (T. cruzi. Nevertheless, it is not fully understood, if ET formation helps the immune system to eliminate intracellular parasites. The goal of this study was to analyze ET formation in response to the intracellular parasite Trypanosma (T. cruzi by granulocytes derived from animals that serve as natural reservoir. Thus, we investigated the ET formation in two T. cruzi reservoirs, namely dogs as domestic animal and common opossums (Didelphis marsupialis as wild animal. Granulocytes were harvested from fresh blood by density gradient centrifugation and afterwards incubated with T. cruzi. We conducted the analysis by determination of free DNA and immunofluorescence microscopy. Using both methods, we show that T. cruzi efficiently induces ET formation in granulocytes derived from common opossum as well as dog blood. Most ETs from both animal species as response to T. cruzi are decorated with the protease neutrophil elastase. Since T. cruzi is well known to circulate over years in both analyzed animals as reservoirs, it may be assumed that T. cruzi efficiently evades ET-mediated killing in those animals. Therefore, ETs may not play a major role in efficient elimination of the pathogen from the blood of dogs or common opossums as T. cruzi survives in niches of their body. The characterization of granulocytes in various animals and humans may be helpful

  14. Enhancement of innate immunity with granulocyte colony-stimulating factor did not mitigate disease in pigs infected with a highly pathogenic Chinese PRRSV strain.

    Science.gov (United States)

    Schlink, Sarah N; Lager, Kelly M; Brockmeier, Susan L; Loving, Crystal L; Miller, Laura C; Vorwald, Ann C; Yang, Han-Chun; Kehrli, Marcus E; Faaberg, Kay S

    2016-10-15

    Porcine reproductive and respiratory syndrome virus (PRRSV) is responsible for one of the most economically important diseases in swine worldwide. It causes reproductive failure in sows and pneumonia in pigs that predisposes them to secondary bacterial infections. Methods to control PRRSV and/or limit secondary bacterial infections are desired to reduce the impact of this virus on animal health. Neutrophils play a major role in combatting infection; they can act as phagocytes as well as produce and release lytic enzymes that have potent antimicrobial effects leading to the destruction and clearance of bacterial pathogens. Granulocyte-colony stimulating factor (G-CSF) is a cytokine that controls the production, differentiation and function of granulocytes (including neutrophils) from the bone marrow. Recent work from our laboratory has shown that encoding porcine G-CSF in a replication-defective adenovirus (Ad5-G-CSF) and delivering a single dose to pigs induced a neutrophilia lasting more than two weeks. As secondary bacterial infection is a common occurrence following PRRSV infection, particularly following challenge with highly pathogenic (HP)-PRRSV, the aim of the current study was to evaluate the effectiveness of a single prophylactic dose of adenovirus-encoded G-CSF to mitigate secondary bacterial disease associated with HP-PRRSV infection. Administration of Ad5-G-CSF induced a significant neutrophilia as expected. However, between 1 and 2days following HP-PRRSV challenge the number of circulating neutrophils decreased dramatically in the HP-PRRSV infected group, but not the non-infected Ad5-G-CSF group. Ad5-G-CSF administration induced monocytosis as well, which was also reduced by HP-PRRSV challenge. There was no difference in the progression of disease between the Ad5-G-CSF and Ad5-empty groups following HP-PRRSV challenge, with pneumonia and systemic bacterial infection occurring in both treatment groups. Given the impact of HP-PRRSV infection on the

  15. Investigating the Adult Ixodid Tick Populations and Their Associated Anaplasma, Ehrlichia, and Rickettsia Bacteria at a Rocky Mountain Spotted Fever Hotspot in Western Tennessee.

    Science.gov (United States)

    Trout Fryxell, Rebecca T; Hendricks, Brain M; Pompo, Kimberly; Mays, Sarah E; Paulsen, Dave J; Operario, Darwin J; Houston, Allan E

    2017-08-01

    Ehrlichiosis and rickettsiosis are two common bacterial tick-borne diseases in the southeastern United States. Ehrlichiosis is caused by ehrlichiae transmitted by Amblyomma americanum and rickettsiosis is caused by rickettsiae transmitted by Amblyomma maculatum and Dermacentor variabilis. These ticks are common and have overlapping distributions in the region. The objective of this study was to identify Anaplasma, Ehrlichia, and Rickettsia species associated with questing ticks in a Rocky Mountain spotted fever (RMSF) hotspot, and identify habitats, time periods, and collection methods for collecting questing-infected ticks. Using vegetation drags and CO 2 -baited traps, ticks were collected six times (May-September 2012) from 100 sites (upland deciduous, bottomland deciduous, grassland, and coniferous habitats) in western Tennessee. Adult collections were screened for Anaplasma and Ehrlichia (simultaneous polymerase chain reaction [PCR]) and Rickettsia using genus-specific PCRs, and resulting positive amplicons were sequenced. Anaplasma and Ehrlichia were only identified within A. americanum (Ehrlichia ewingii, Ehrlichia chaffeensis, Panola Mountain Ehrlichia, and Anaplasma odocoilei sp. nov.); more Ehrlichia-infected A. americanum were collected at the end of June regardless of habitat and collection method. Rickettsia was identified in three tick species; "Candidatus Rickettsia amblyommii" from A. americanum, R. parkeri and R. andeanae from A. maculatum, and R. montanensis ( = montana) from D. variabilis. Overall, significantly more Rickettsia-infected ticks were identified as A. americanum and A. maculatum compared to D. variabilis; more infected-ticks were collected from sites May-July and with dragging. In this study, we report in the Tennessee RMSF hotspot the following: (1) Anaplasma and Ehrlichia are only found in A. americanum, (2) each tick species has its own Rickettsia species, (3) a majority of questing-infected ticks are collected May-July, (4) A

  16. Experimental inoculation of beagle dogs with Ehrlichia species detected from Ixodes ovatus

    OpenAIRE

    Watanabe, Malaika; Oikawa, T; Hiraoka, Hiroko; Kaneko, N; Itamoto, Kazuhito; Mizuno, Tohru; Okuda, Masaru; Inokuma, Hisashi

    2006-01-01

    Three beagle dogs were inoculated with mice spleen/liver homogenate infected with Ehrlichia species detected from Ixodes ovatus (EIO) and one dog was used as a control. All three infected dogs did not show clinical signs of disease except for mild pyrexia throughout the 41-day study period. Splenomegaly was observed from Day 7 post-inoculation (p.i.) in two of the dogs. Hematological and biochemical abnormalities included mild thrombocytopenia, hypoproteinaemia, hypoalbuminaemia and increased...

  17. Seroprevalence of Ehrlichia canis, Ehrlichia chaffeensis and Ehrlichia ewingii in dogs in North America

    Directory of Open Access Journals (Sweden)

    Beall Melissa J

    2012-02-01

    Full Text Available Abstract Background This study evaluated the exposure of dogs to three different Ehrlichia spp. in the south and central regions of the United States where vector-borne disease prevalence has been previously difficult to ascertain, particularly beyond the metropolitan areas. Methods Dog blood samples (n = 8,662 were submitted from 14 veterinary colleges, 6 private veterinary practices and 4 diagnostic laboratories across this region. Samples were tested for E. canis, E. chaffeensis and E. ewingii specific antibodies using peptide microtiter ELISAs. Results Overall, E. canis, E. chaffeensis and E. ewingii seroprevalence was 0.8%, 2.8%, and 5.1%, respectively. The highest E. canis seroprevalence (2.3% was found in a region encompassing Arkansas, Louisiana, Oklahoma, Tennessee and Texas. E. chaffeensis seroreactivity was 6.6% in the central region (Arkansas, Kansas, Missouri, and Oklahoma and 4.6% in the southeast region (Georgia, Maryland, North Carolina, South Carolina, Tennessee and Virginia. Seroreactivity to E. ewingii was also highest in the central region (14.6% followed by the southeast region (5.9%. The geospatial pattern derived from E. chaffeensis and E. ewingii seropositive samples was similar to previous reports based on E. chaffeensis seroreactivity in white-tailed deer and the distribution of human monocytic ehrlichiosis (HME cases reported by the CDC. Conclusions The results of this study provide the first large scale regional documentation of exposure to E. canis, E. chaffeensis and E. ewingii in pet dogs, highlighting regional differences in seroprevalence and providing the basis for heightened awareness of these emerging vector-borne pathogens by veterinarians and public health agencies.

  18. Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection.

    Directory of Open Access Journals (Sweden)

    Sonali Singh

    Full Text Available Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF, on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1 and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human

  19. Granulocyte-macrophage colony stimulatory factor enhances the pro-inflammatory response of interferon-γ-treated macrophages to Pseudomonas aeruginosa infection.

    Science.gov (United States)

    Singh, Sonali; Barr, Helen; Liu, Yi-Chia; Robins, Adrian; Heeb, Stephan; Williams, Paul; Fogarty, Andrew; Cámara, Miguel; Martínez-Pomares, Luisa

    2015-01-01

    Pseudomonas aeruginosa is an opportunistic pathogen that can cause severe infections at compromised epithelial surfaces, such those found in burns, wounds, and in lungs damaged by mechanical ventilation or recurrent infections, particularly in cystic fibrosis (CF) patients. CF patients have been proposed to have a Th2 and Th17-biased immune response suggesting that the lack of Th1 and/or over exuberant Th17 responses could contribute to the establishment of chronic P. aeruginosa infection and deterioration of lung function. Accordingly, we have observed that interferon (IFN)-γ production by peripheral blood mononuclear cells from CF patients positively correlated with lung function, particularly in patients chronically infected with P. aeruginosa. In contrast, IL-17A levels tended to correlate negatively with lung function with this trend becoming significant in patients chronically infected with P. aeruginosa. These results are in agreement with IFN-γ and IL-17A playing protective and detrimental roles, respectively, in CF. In order to explore the protective effect of IFN-γ in CF, the effect of IFN-γ alone or in combination with granulocyte-macrophage colony-stimulating factor (GM-CSF), on the ability of human macrophages to control P. aeruginosa growth, resist the cytotoxicity induced by this bacterium or promote inflammation was investigated. Treatment of macrophages with IFN-γ, in the presence and absence of GM-CSF, failed to alter bacterial growth or macrophage survival upon P. aeruginosa infection, but changed the inflammatory potential of macrophages. IFN-γ caused up-regulation of monocyte chemoattractant protein-1 (MCP-1) and TNF-α and down-regulation of IL-10 expression by infected macrophages. GM-CSF in combination with IFN-γ promoted IL-6 production and further reduction of IL-10 synthesis. Comparison of TNF-α vs. IL-10 and IL-6 vs. IL-10 ratios revealed the following hierarchy in regard to the pro-inflammatory potential of human macrophages

  20. Granulocyte migration in uncomplicated intestinal anastomosis in man

    Energy Technology Data Exchange (ETDEWEB)

    Keshavarzian, A.; Gibson, R.; Guest, J.; Spencer, J.; Lavender, J.P.; Hodgson, H.J.

    1986-03-01

    We have investigated the presence, duration, and clinical significance of granulocyte accumulation, using indium-111 granulocyte scanning, in patients following uncomplicated intestinal anastomosis. Eight patients underwent intestinal resection and anastomosis (right hemicolectomy, 5; sigmoid colectomy, 2; ileal resection, 1) for carcinoma, angiodysplasia, or perforation. All patients had an uneventful postoperative course, with no evidence of any leakage or infection. Indium-111 granulocyte scan and abdominal ultrasound were performed 7-20 days (12 +/- 4.7 means +/- SD) following surgery. Indium-111 granulocyte scan showed the presence of labeled granulocytes at the site of anastomosis in all patients. In three of eight, cells subsequently passed into the lumen of the bowel. In contrast, granulocytes were not visualized along the abdominal incision. Thus, in contrast to skin wounds, granulocytes continue migrating into the intestinal wall in areas of anastomosis for at least up to 20 days following surgical trauma. They may play a significant role both in healing the anastomosis and in preventing systemic bacterial infection. Moreover, indium-111 granulocyte scans following intestinal surgery should be interpreted with care, and the presence of labeled granulocytes around anastomoses does not necessarily indicate abscess formation.

  1. Granulocyte migration in uncomplicated intestinal anastomosis in man

    International Nuclear Information System (INIS)

    Keshavarzian, A.; Gibson, R.; Guest, J.; Spencer, J.; Lavender, J.P.; Hodgson, H.J.

    1986-01-01

    We have investigated the presence, duration, and clinical significance of granulocyte accumulation, using indium-111 granulocyte scanning, in patients following uncomplicated intestinal anastomosis. Eight patients underwent intestinal resection and anastomosis (right hemicolectomy, 5; sigmoid colectomy, 2; ileal resection, 1) for carcinoma, angiodysplasia, or perforation. All patients had an uneventful postoperative course, with no evidence of any leakage or infection. Indium-111 granulocyte scan and abdominal ultrasound were performed 7-20 days (12 +/- 4.7 means +/- SD) following surgery. Indium-111 granulocyte scan showed the presence of labeled granulocytes at the site of anastomosis in all patients. In three of eight, cells subsequently passed into the lumen of the bowel. In contrast, granulocytes were not visualized along the abdominal incision. Thus, in contrast to skin wounds, granulocytes continue migrating into the intestinal wall in areas of anastomosis for at least up to 20 days following surgical trauma. They may play a significant role both in healing the anastomosis and in preventing systemic bacterial infection. Moreover, indium-111 granulocyte scans following intestinal surgery should be interpreted with care, and the presence of labeled granulocytes around anastomoses does not necessarily indicate abscess formation

  2. Detection of a Rickettsia Closely Related to Rickettsia aeschlimannii, “Rickettsia heilongjiangensis,” Rickettsia sp. Strain RpA4, and Ehrlichia muris in Ticks Collected in Russia and Kazakhstan

    OpenAIRE

    Shpynov, Stanislav; Fournier, Pierre-Edouard; Rudakov, Nikolay; Tankibaev, Marat; Tarasevich, Irina; Raoult, Didier

    2004-01-01

    Using PCR, we screened 411 ticks from four genera collected in Russia and Kazakhstan for the presence of rickettsiae and ehrlichiae. In Russia, we detected “Rickettsia heilongjiangensis,” Rickettsia sp. strain RpA4, and Ehrlichia muris. In Kazakhstan, we detected Rickettsia sp. strain RpA4 and a rickettsia closely related to Rickettsia aeschlimannii. These agents should be considered in a differential diagnosis of tick-borne infections in these areas.

  3. Molecular detection of Anaplasma bovis, Ehrlichia canis and Hepatozoon felis in cats from Luanda, Angola.

    Science.gov (United States)

    Oliveira, Ana Cristina; Luz, Maria Francisca; Granada, Sara; Vilhena, Hugo; Nachum-Biala, Yaarit; Lopes, Ana Patrícia; Cardoso, Luís; Baneth, Gad

    2018-03-20

    Molecular identification of tick-borne pathogen infection in cats from Africa is scarce. The presence of bacterial (Anaplasma and Ehrlichia) and protozoal (Babesia and Hepatozoon) agents was investigated in blood samples from 102 domestic cats from Luanda, Angola, by polymerase chain reaction and DNA sequencing. Three cats (2.9%) were found infected with Ehrlichia canis, three (2.9%) with Hepatozoon felis and one (1.0%) with Anaplasma bovis. The prevalence of infections with one single agent was 4.9%, and that of infection with two agents (i.e. E. canis and H. felis) was 1.0%. In total, six cats (5.9%) were found infected with at least one of the detected tick-borne agents. This is the first report of A. bovis, E. canis and H. felis in cats from Angola. To the best of our knowledge, A. bovis is also being reported for the first time in domestic cats outside of Japan. Cats are at a low to moderate risk of being infected with tick-borne agents in Luanda.

  4. Serodetection of Ehrlichia canis amongst dogs in central Namibia

    Directory of Open Access Journals (Sweden)

    Rutendo Manyarara

    2015-06-01

    Full Text Available Ehrlichia canis is a major pathogen in dogs throughout Africa, yet it has not been reported in Namibia. The aim of this study was to determine the seroprevalence of canine ehrlichiosis in central Namibia using the ImmunoComb assay (Biogal, Galed Laboratories. The study included 76 dogs that presented to the Rhino Park Veterinary Clinic in the north-western suburb of Khomasdal, Windhoek, Namibia, as well as 30 stray dogs from the Windhoek branch of the Society for the Prevention of Cruelty to Animals. Of the 106 dogs tested, 53.8% were seropositive at titres > 1:80. Dogs that presented with symptoms of E. canis infection had a significantly higher seroprevalence (86.6% compared with apparently healthy dogs (41.6% (P = 0.00. Location of habitation was significant (P < 0.017, with a high percentage of dogs exposed to E. canis living in the northern or north-western part of Windhoek. As the first study to serologically establish E. canis as a major pathogen in dogs in central Namibia, it is notable that the highest proportion of seropositive dogs came from low-income areas. Further investigation is necessary to describe the ecology of this important tick-borne pathogen of companion animals in Namibia.

  5. Molecular Characterization and Phylogenetic Analysis of Anaplasma spp. and Ehrlichia spp. Isolated from Various Ticks in Southeastern and Northwestern Regions of Iran.

    Science.gov (United States)

    Jafar Bekloo, Ahmad; Ramzgouyan, Maryam Roya; Shirian, Sadegh; Faghihi, Faezeh; Bakhshi, Hassan; Naseri, Fatemeh; Sedaghat, Mehdi; Telmadarraiy, Zakkyeh

    2018-05-01

    Anaplasma/Ehrlichia species are tick-transmitted pathogens that cause infections in humans and numerous domestic and wild animal species. There is no information available on the molecular characteristics and phylogenetic position of Anaplasma/Ehrlichia spp. isolated from tick species from different geographic locations in Iran. The aim of this study was to determine the prevalence, molecular characteristics, and phylogenetic relationship of both Anaplasma spp. and Ehrlichia spp. in tick species isolated from different domestic animals from two different geographical locations of Iran. A total of 930 ticks were collected from 93 cattle, 250 sheep, and 587 goats inhabiting the study areas. The collected ticks were then investigated for the presence of Anaplasma/Ehrlichia spp. using nested PCR based on the 16S rRNA gene, followed by sequencing. Sequence analysis was done based on the data published in the GenBank on Anaplasma/Ehrlichia spp. isolates using bioinformatic tools such as the standard nucleotide BLAST. Genome of Anaplasma or Ehrlichia spp. was detected in 14 ticks collected in Heris, including 5 Dermacentor marginatus, 1 Haemaphysalis erinacei, 3 Hyalomma anatolicum, and 4 Rhipicephalus sanguineus, also in 29 ticks collected in Chabahar, including 14 R. sanguineus, 8 D. marginatus, 3 Hyalomma Anatolicum, and 4 Hyalomma dromedarii. Partial analysis of the 16S rRNA gene sequence of positive samples collected from goats and sheep showed that they were infected with Anaplasma/Ehrlichia spp. that were 94-98% identical to ovine Anaplasma and 91-96% identical to Neoehrlichia and Ehrlichia spp. The various ticks identified in this study suggest the possible emergence of tick-borne diseases in animals and humans in these regions. R. sanguineus and D. marginatus seem to be predominant vectors responsible for anaplasmosis in these regions. Partial sequence analysis of the 16S rRNA gene showed that A. ovis is genetically polymorphic in these regions. Furthermore, an

  6. An Ehrlichia strain from a llama (Lama glama) and Llama-associated ticks (Ixodes pacificus).

    Science.gov (United States)

    Barlough, J E; Madigan, J E; Turoff, D R; Clover, J R; Shelly, S M; Dumler, J S

    1997-01-01

    An ehrlichia was identified in the blood of a diseased llama (lama glama). Sequencing of its 16S rRNA gene showed the ehrlichia to be closely related to members of the Ehrlichia phagocytophila genogroup. The agent was also found in a pool of ticks (Ixodes pacificus) collected at the llama site. PMID:9157118

  7. Iron Starvation Conditions Upregulate Ehrlichia ruminantium Type IV Secretion System, tr1 Transcription Factor and map1 Genes Family through the Master Regulatory Protein ErxR

    Directory of Open Access Journals (Sweden)

    Amal Moumène

    2018-01-01

    Full Text Available Ehrlichia ruminantium is an obligatory intracellular bacterium that causes heartwater, a fatal disease in ruminants. Due to its intracellular nature, E. ruminantium requires a set of specific virulence factors, such as the type IV secretion system (T4SS, and outer membrane proteins (Map proteins in order to avoid and subvert the host's immune response. Several studies have been conducted to understand the regulation of the T4SS or outer membrane proteins, in Ehrlichia, but no integrated approach has been used to understand the regulation of Ehrlichia pathogenicity determinants in response to environmental cues. Iron is known to be a key nutrient for bacterial growth both in the environment and within hosts. In this study, we experimentally demonstrated the regulation of virB, map1, and tr1 genes by the newly identified master regulator ErxR (for Ehrlichia ruminantium expression regulator. We also analyzed the effect of iron depletion on the expression of erxR gene, tr1 transcription factor, T4SS and map1 genes clusters in E. ruminantium. We show that exposure of E. ruminantium to iron starvation induces erxR and subsequently tr1, virB, and map1 genes. Our results reveal tight co-regulation of T4SS and map1 genes via the ErxR regulatory protein at the transcriptional level, and, for the first time link map genes to the virulence function sensu stricto, thereby advancing our understanding of Ehrlichia's infection process. These results suggest that Ehrlichia is able to sense changes in iron concentrations in the environment and to regulate the expression of virulence factors accordingly.

  8. Bacteria of the genera Ehrlichia and Rickettsia in ticks of the family Ixodidae with medical importance in Argentina.

    Science.gov (United States)

    Sebastian, Patrick S; Tarragona, Evelina L; Bottero, María N Saracho; Mangold, Atilio J; Mackenstedt, Ute; Nava, Santiago

    2017-01-01

    The aim of this study was to get an overview about the occurrence of bacteria from the genus Ehrlichia and Rickettsia in ixodid ticks with medical importance in Argentina. Therefore, in 2013 and 2014, free-living ticks were collected in different provinces of northern Argentina. These ticks were determined as Amblyomma sculptum, Amblyomma neumanni, Amblyomma parvum, Amblyomma triste, Amblyomma ovale, Amblyomma tonelliae and Haemaphysalis juxtakochi. All samples were tested to determine the infection with Ehrlichia spp. and Rickettsia spp. by PCR assays. Rickettsial DNA was detected in all tested tick species, with the exception of A. tonelliae. 'Candidatus Rickettsia amblyommii', 'Candidatus Rickettsia andeanae', and Rickettsia parkeri were found in A. neumanni, A. parvum, and A. triste, respectively. Another rickettsial species, Rickettsia bellii, was found in A. sculptum, A. ovale and H. juxtakochi. None of the tested ticks showed infection with Ehrlichia. The results of the study demonstrate that Rickettsia species belonging to the spotted fever group are associated with various species of Amblyomma throughout a wide area of northern Argentina, where cases of Amblyomma ticks biting humans are common.

  9. Ticks circulate Anaplasma, Ehrlichia, Babesia and Theileria parasites in North of Iran.

    Science.gov (United States)

    Bekloo, Ahmad Jafar; Bakhshi, Hasan; Soufizadeh, Ayoub; Sedaghat, Mohammad Mehdi; Bekloo, Romina Jafar; Ramzgouyan, Maryam Roya; Chegeni, Asadollah Hosseini; Faghihi, Faezeh; Telmadarraiy, Zakkyeh

    2017-12-15

    Ticks serve as important vectors of some pathogens of medical importance all over the world and identification of their rate of infection plays an important role for further control of diseases. In the current study, we investigated on ticks collected from north of Iran where raising and caring livestock are the main task of the people in order to find evidences of infection of Babesia, Theileria, Anaplasma and Ehrlichia microbial agents. Totally, 609 hard tick species from two genera Hyalomma and Rhipicephalus including; Hy. scupense, Hy. dromedarii, Hy. rufipes, Hy. marginatum, Hy. asiaticum, Hy. anatolicum, R. bursa, R. sanguineus and R. turanicus were identified. Molecular analysis revealed the presence of Anaplasma, Ehrlichia, Babesia and Theileria microorganism agents in all collected tick species except Hy. asiaticum and R. turanicus. To the best of our knowledge, this is the first report on identification of B. occultans in Hyalomma anatolicum and B. ovis in Hyalomma sp in Iran. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Indium-granulocyte scanning in the painful prosthetic joint

    International Nuclear Information System (INIS)

    Pring, D.J.; Henderson, R.G.; Keshavarzian, A.; Rivett, A.G.; Krausz, T.; Coombs, R.R.; Lavender, J.P.

    1986-01-01

    The value of indium-111-labeled granulocyte scanning to determine the presence of infection was assessed in 50 prosthetic joints (41 of which were painful) in 40 patients. Granulocytes were obtained from the patients' blood and labeled in plasma with indium 111 tropolonate. Abnormal accumulation of indium 111 in the region of the prosthesis was noted. Proven infection occurred in 11 prostheses, and all of the infections were detected by indium-111-labeled granulocyte scanning. Nineteen were not infected (including nine asymptomatic controls) and only two produced false-positive scans. This represents a specificity of 89.5%, sensitivity of 100%, and overall accuracy of 93.2%. These results compare favorably with plain radiography. There was no radiologic evidence of infection in three of the infected prostheses, and 10 of the noninfected prostheses had some radiologic features that suggested sepsis. We conclude that indium-granulocyte scanning can reliably detect or exclude infection in painful prosthetic joints and should prove useful in clinical management

  11. The pCS20 PCR assay for Ehrlichia ruminantium does not cross-react with the novel deer ehrlichial agent found in white-tailed deer in the United States of America

    Directory of Open Access Journals (Sweden)

    S.M. Mahan

    2004-11-01

    Full Text Available White-tailed deer are susceptible to heartwater (Ehrlichia [Cowdria] ruminantium infection and are likely to suffer high mortality if the disease spreads to the United States. It is vital, therefore, to validate a highly specific and sensitive detection method for E. ruminantium infection that can be reliably used in testing white-tailed deer, which are reservoirs of antigenically or genetically related agents such as Ehrlichia chaffeensis, Anaplasma (Ehrlichia phagocytophilum (HGE agent and Ehrlichia ewingii. Recently, a novel but as yet unnamed ehrlichial species, the white-tailed deer ehrlichia (WTDE, has been discovered in deer populations in the United States. Although the significance of WTDE as a pathogen is unknown at present, it can be distinguished from other Ehrlichia spp. based on 16S rRNA gene sequence analysis. In this study it was differentiated from E. ruminantium by the use of the pCS20 PCR assay which has high specificity and sensitivity for the detection of E. ruminantium. This assay did not amplify DNA from the WTDE DNA samples isolated from deer resident in Florida, Georgia and Missouri, but amplified the specific 279 bp fragment from E. ruminantium DNA. The specificity of the pCS20 PCR assay for E. ruminantium was confirmed by Southern hybridization. Similarly, the 16S PCR primers (nested that amplify a specific 405-412 bp fragment from the WTDE DNA samples, did not amplify any product from E. ruminantium DNA. This result demonstrates that it would be possible to differentiate between E. ruminantium and the novel WTDE agent found in white tailed deer by applying the two respective PCR assays followed by Southern hybridizations. Since the pCS20 PCR assay also does not amplify any DNA products from E. chaffeensis or Ehrlichia canis DNA, it is therefore the method of choice for the detection of E. ruminantium in these deer and other animal hosts.

  12. Effect of granulocyte colony-stimulating factor (G-CSF) in human immunodeficiency virus-infected patients: increase in numbers of naive CD4 cells and CD34 cells makes G-CSF a candidate for use in gene therapy or to support antiretroviral therapy

    DEFF Research Database (Denmark)

    Nielsen, S D; Afzelius, P; Dam-Larsen, S

    1998-01-01

    The potential of granulocyte colony-stimulating factor (G-CSF) to mobilize CD4 cells and/or CD34 cells for use in gene therapy or to support antiretroviral therapy was examined. Ten human immunodeficiency virus-infected patients were treated with G-CSF (300 microg/day) for 5 days. Numbers of CD4.......01/microL (P CSF induced increases in numbers of CD34 cells and CD4 cells in HIV-infected patients...

  13. Positive /sup 111/In-granulocyte scintigraphy in a patient with focal leukemic blast cell infiltrations

    Energy Technology Data Exchange (ETDEWEB)

    Syrjaelae, M; Remes, K; Paavonen, T; Liewendahl, K

    1985-06-01

    A patient with acute myeloid leukemia was investigated with /sup 111/In-granulocyte scintigraphy to reveal possible sites of infection. /sup 111/In-granulocytes accumulated in areas of leukemia blast cell infiltration leading to a false-positive scintigram. This possibility must be kept in mind when studying leukemic patients using labeled leukocytes.

  14. Rangelia vitalii, Babesia spp. and Ehrlichia spp. in dogs in Passo Fundo, state of Rio Grande do Sul, Brazil

    Directory of Open Access Journals (Sweden)

    Juliana Gottlieb

    2016-06-01

    Full Text Available Abstract Pathogens transmitted by ticks are an emerging problem worldwide, this study aimed to diagnose the causal agents of infection in dogs presenting suspected hemoparasitoses. Fifty-eight dogs with clinical signs such as depression, hemorrhagic diathesis and fever were evaluated regarding clinical presentation, hemogram, blood smears and serological tests, using the indirect immunofluorescence method for the agents Babesia vogeli and Ehrlichia canis and conventional PCR for Babesia spp. (gene 18S rRNA, Rangelia vitalii (gene 18S rRNA and Ehrlichia spp. (gene dsb. Five (8.6% of the 58 dogs were serologically positive for Babesia spp. and three (5.1% for E. canis. Four dogs (6.8% were positive for R. vitalii through the molecular diagnosis. The PCR products were sequenced and the DNA from R. vitalii was found to be 99% genetically identical to samples of R. vitalii that had been isolated in Brazil. No presence of Babesia spp. or E. canis was observed through PCR on the dogs evaluated here. The results indicate the presence of R. vitalii and exposure to Babesia spp. and Ehrlichia spp. among the dogs analyzed.

  15. Development of multiplex polymerase chain reaction for detection of Ehrlichia canis, Babesia spp and Hepatozoon canis in canine blood.

    Science.gov (United States)

    Kledmanee, Kan; Suwanpakdee, Sarin; Krajangwong, Sakranmanee; Chatsiriwech, Jarin; Suksai, Parut; Suwannachat, Pongpun; Sariya, Ladawan; Buddhirongawatr, Ruangrat; Charoonrut, Phingphol; Chaichoun, Kridsada

    2009-01-01

    A multiplex polymerase chain reaction (PCR) has been developed for simultaneous detection of canine blood parasites, Ehrlichia canis, Babesia spp and Hepatozoon canis, from blood samples in a single reaction. The multiplex PCR primers were specific to E. canis VirB9, Babesia spp 16S rRNA and H. canis 16S rRNA genes. Specificity of the amplicons was confirmed by DNA sequencing. The assay was evaluated using normal canine and infected blood samples, which were detected by microscopic examination. This multiplex PCR offers scope for simultaneous detection of three important canine blood parasites and should be valuable in monitoring parasite infections in dogs and ticks.

  16. Acquired agranulocytosis with granulocyte specific cytotoxic autoantibody.

    Science.gov (United States)

    Blaschke, J; Goeken, N E; Thompson, J S; Dick, F R; Gingrich, R D

    1979-05-01

    Multiple infections and severe neutropenia were found in a previously healthy 29 year old man with no history of similar syndromes in the family, drug ingestion or exposure to environmental toxins. There was no evidence at the time of presentation of diseases previously associated with agranulocytosis (e.g., neoplasia, thyrotoxicosis, chronic infection, collagen-vascular disease or leukoagglutinating antibody). His serum contained a nonagglutinating, complement-dependent, cytotoxic antibody, however, reactive with peripheral blood granulocytes from 35 per cent of normal donors. The neutropenia was not affected by steroids but resolved promptly after splenectomy. Microscopic examination of the spleen revealed ingestion of polymorphonuclear leukocytes by splenic macrophages. Family studies indicated that the target antigen was non-HLA and that the antibody was not absorbed by lymphocytes or platelets. We conclude that the agranulocytosis was autoimmune in origin and suggest that similar myeloid-specific immune responses could influence granulocyte tranfusion and bone marrow transplantation by alloimmune "rejection" that would not be avoided by matching only for HLA specificities.

  17. Eighteen years experience of granulocyte donations-acceptable donor safety?

    Science.gov (United States)

    Axdorph Nygell, Ulla; Sollén-Nilsson, Agneta; Lundahl, Joachim

    2015-10-01

    Granulocyte transfusions are given to patients with life-threatening infections, refractory to treatment. The donors are stimulated with corticosteroids ± granulocyte colony stimulating factor (G-CSF). However, data regarding the donors' safety is sparse. The objective was therefore to evaluate short- and long-term adverse events (AE) in G-CSF stimulated donors. All consecutive granulocyte donors from 1994 to 2012 were identified through our registry. From the donation records, the number of aphereses, stimulation therapy, AE, blood values post donation, and recent status were evaluated. One hundred fifty-four volunteer donors were mobilized for 359 collections. Age at first granulocyte donation was 43 years (median; range 19-64 years). Follow-up was 60 months (median; range 0-229 months). The dose of G-CSF per collection was 3.8 ug/kg body weight (median; range 1.6-6.0 ug/kg). Sedimentation agent was HES. Short-term AE were mild. Blood values 4 weeks post donation with minor reductions/elevations mostly resolved in later donations. Fourteen donors were excluded from the registry due to hypertension (4), diabetes (2), atrial flutter (1), breast carcinoma (1), urethral carcinoma in situ (1), MGUS (1), thrombosis (1), anaphylaxis (1), primary biliary cirrhosis (1), and unknown (1). Three donors are deceased due to diabetes, acute myocardial infarction, and unknown cause. All excluded/deceased donors except one were excluded/died at least 6 months after first granulocyte donation. No serious short-term AE were observed. Due to the variability of diagnoses among excluded/deceased donors, we propose that it is less likely that granulocyte donations have a causative impact on these donors' exclusion or death. © 2014 Wiley Periodicals, Inc.

  18. Survey of Ehrlichia canis, Babesia spp. and Hepatozoon spp. in dogs from a semiarid region of Brazil

    Directory of Open Access Journals (Sweden)

    Tereza Emmanuelle de Farias Rotondano

    Full Text Available This study assessed the occurrence of Ehrlichia spp., Babesia spp. and Hepatozoon spp. infections in 100 tick-harboring dogs from a semiarid region of the State of Paraíba, Northeastern Brazil. Blood samples and ticks were collected from the animals, and a questionnaire was submitted to dog owners to obtain general data. Blood samples were used to perform hemogram, direct blood smear and immunological and molecular hemoparasite detection. The 1,151 ticks collected were identified as Rhipicephalus sanguineus; direct smears revealed E. canis-like morulae in the monocytes of 4% (4/100 of the non-vaccinated female dogs, and 34% and 25% of the dogs tested positive for Ehrlichia canis by indirect immunofluorescence assay (IFA and polymerase chain reaction (PCR, respectively. Blood smear examination revealed Babesia-suggestive merozoites in the erythrocytes of 2% (2/100 of the animals. Babesia vogeli was detected by PCR in ten animals (10% and was correlated with young age (p = 0.007 and thrombocytopenia (p = 0.01. None of the animals showed Hepatozoon spp. positivity. These results indicate that E. canis is the main tick-borne canine pathogen in the study area and provide the first report of B. vogeli infection in dogs from Paraiba State.

  19. Survey of Ehrlichia canis, Babesia spp. and Hepatozoon spp. in dogs from a semiarid region of Brazil.

    Science.gov (United States)

    Rotondano, Tereza Emmanuelle de Farias; Almeida, Herta Karyanne Araújo; Krawczak, Felipe da Silva; Santana, Vanessa Lira; Vidal, Ivana Fernandes; Labruna, Marcelo Bahia; de Azevedo, Sérgio Santos; Ade lmeida, Alzira Maria Paiva; de Melo, Marcia Almeida

    2015-01-01

    This study assessed the occurrence of Ehrlichia spp., Babesia spp. and Hepatozoon spp. infections in 100 tick-harboring dogs from a semiarid region of the State of Paraíba, Northeastern Brazil. Blood samples and ticks were collected from the animals, and a questionnaire was submitted to dog owners to obtain general data. Blood samples were used to perform hemogram, direct blood smear and immunological and molecular hemoparasite detection. The 1,151 ticks collected were identified as Rhipicephalus sanguineus; direct smears revealed E. canis-like morulae in the monocytes of 4% (4/100) of the non-vaccinated female dogs, and 34% and 25% of the dogs tested positive for Ehrlichia canis by indirect immunofluorescence assay (IFA) and polymerase chain reaction (PCR), respectively. Blood smear examination revealed Babesia-suggestive merozoites in the erythrocytes of 2% (2/100) of the animals. Babesia vogeli was detected by PCR in ten animals (10%) and was correlated with young age (p = 0.007) and thrombocytopenia (p = 0.01). None of the animals showed Hepatozoon spp. positivity. These results indicate that E. canis is the main tick-borne canine pathogen in the study area and provide the first report of B. vogeli infection in dogs from Paraiba State.

  20. Irradiation for conjunctival granulocytic sarcoma

    International Nuclear Information System (INIS)

    Fleckenstein, K.; Geinitz, H.; Grosu, A.; Molls, M.; Goetze, K.; Werner, M.

    2003-01-01

    Case History and Findings: A 73-year-old woman with a history of myeloproliferative syndrome (MPS) presented with bilateral chemosis, redness and burning of the eyes. The ocular motility was severely impaired. Ophthalmological examination revealed markedly distended conjunctivas on both sides. Biopsy disclosed conjunctival granulocytic sarcoma as an initial symptom of acute myelogenous leukemia (AML). Diagnosis was confirmed by peripheral blood smear and bone marrow aspiration. Treatment and Outcome: The orbital tumor disappeared completely after local external beam irradiation with a total dose of 30 Gy and no further orbital recurrence occurred. With chemotherapy following irradiation transient hematological remission was achieved. 5 months after diagnosis the patient died of respiratory failure following atypical pneumonia as a consequence of her underlying disorder. Conclusion: Detection of orbital granulocytic sarcoma, even in the absence of typical leukemic symptoms is of practical importance, because treatment with irradiation can lead to stabilization or improvement in the patient's vision. (orig.)

  1. Prevalence and diversity of Babesia, Hepatozoon, Ehrlichia, and Bartonella in wild and domestic carnivores from Zambia, Africa.

    Science.gov (United States)

    Williams, Brianna M; Berentsen, Are; Shock, Barbara C; Teixiera, Maria; Dunbar, Michael R; Becker, Matthew S; Yabsley, Michael J

    2014-03-01

    A molecular survey was conducted for several hemoparasites of domestic dogs and three species of wild carnivores from two sites in Zambia. Three Babesia spp. were detected including Babesia felis and Babesia leo in lions (Panthera leo) and a Babesia sp. (similar to Babesia lengau) in spotted hyenas (Crocuta crocuta) and a single lion. All wild dogs (Lycaon pictus) and domestic dogs were negative for Babesia. High prevalences for Hepatozoon were noted in all three wild carnivores (38-61%) and in domestic dogs (13%). Significantly higher prevalences were noted in hyenas and wild dogs compared with domestic dogs and lions. All carnivores were PCR negative for Ehrlichia canis, Ehrlichia ewingii, and Bartonella spp. Overall, high prevalences and diversity of Babesia and Hepatozoon were noted in wild carnivores from Zambia. This study is the first molecular characterization of Babesia from any hyena species and is the first report of a Babesia sp. closely related to B. lengau, a parasite previously only reported from cheetahs (Acinonyx jubatus), in lions and hyenas. Although usually benign in wild carnivores, these hemoparasites can be pathogenic under certain circumstances. Importantly, data on vectors for these parasites are lacking, so studies are needed to identify vectors as well as determine transmission routes, infection dynamics, and host specificity of these hemoparasites in wildlife in Africa and also the risk of transmission between domestic animals and wildlife.

  2. Detection of Ehrlichia chaffeensis in adult and nymphal stage lone star ticks (Amblyomma americanum) from Long Island, New York

    Science.gov (United States)

    Mixson, T.R.; Ginsberg, H.S.; Campbell, S.R.; Sumner, J.W.; Paddock, C.D.

    2004-01-01

    The lone star tick, Amblyomma americanum (L.), has increased in abundance in several regions of the northeastern United States, including areas of Long Island, NY. Adult and nymphal stage A. americanum collected from several sites on Long Island were evaluated for infection with Ehrlichia chaffeensis, the causative agent of human monocytic ehrlichiosis (HME), by using a nested polymerase chain reaction assay. Fifty-nine (12.5%) of ,17.3 adults and eight of 11.3 pools of five nymphs each (estimated minimum prevalence of infection 1.4%) contained DNA of E. chaffeensis. These data, coupled with the documented expansion of lone star tick populations in the northeastern United States, confirm that E. chaffeensis is endemic to many areas of Long Island and that HME should be considered among the differential diagnoses of the many distinct tick-borne diseases that occur in this region.

  3. First isolation and molecular characterization of Ehrlichia canis in Costa Rica, Central America.

    Science.gov (United States)

    Romero, L E; Meneses, A I; Salazar, L; Jiménez, M; Romero, J J; Aguiar, D M; Labruna, M B; Dolz, G

    2011-08-01

    The present study investigated Ehrlichia species in blood samples from dogs suspected of clinical ehrlichiosis, using molecular and isolation techniques in cell culture. From a total of 310 canine blood samples analyzed by 16S rRNA nested PCR, 148 (47.7%) were positive for Ehrlichia canis. DNA from Ehrlichia chaffeensis or Ehrlichia ewingii was not detected in any sample using species-specific primers in separated reactions. Leukocytes from five PCR-positive dogs were inoculated into DH82 cells; successful isolation of E. canis was obtained in four samples. Partial sequence of the dsb gene of eight canine blood samples (including the five samples for in vitro isolation) was obtained by PCR and their analyses through BLAST showed 100% of identity with the corresponding sequence of E. canis in GenBank. This study represents the first molecular diagnosis, isolation, and molecular characterization of E. canis in dogs from Costa Rica. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Testicular granulocytic sarcoma without systemic leukemia

    NARCIS (Netherlands)

    Lagerveld, B. W.; Wauters, C. A. P.; Karthaus, H. F. M.

    2005-01-01

    This case report describes a unilateral testicular granulocytic sarcoma or chloroma. Because of the relatively immature nature of the tumor cells, the histological diagnosis can be difficult. Granulocytic sarcomas are well known in patients with systemic leukemia and can sometimes precede a systemic

  5. Molecular epidemiology of parasitic protozoa and Ehrlichia canis in wildlife in Madrid (central Spain).

    Science.gov (United States)

    Criado-Fornelio, Angel; Martín-Pérez, T; Verdú-Expósito, C; Reinoso-Ortiz, S A; Pérez-Serrano, J

    2018-07-01

    Wildlife species are involved in the transmission of diverse pathogens. This study aimed to monitor raccoons (Procyon lotor), American minks (Neovison vison), and red foxes (Vulpes vulpes) as potential reservoirs in central Spain. Specifically, 200 spleen and fecal samples (from 194 raccoons, 3 minks, and 3 foxes) were analyzed molecularly by PCR/qPCR and sequencing for the presence of piroplasmids, Hepatozoon spp., Toxoplasma gondii, and Ehrlichia canis infections in the Community of Madrid (Spain). Biological samples were obtained in the years 2014, 2015, and 2016. No pathogen DNA was found in fecal samples. In contrast, analysis of raccoon spleen samples revealed that Toxoplasma was the most prevalent pathogen (prevalence 3.6 ± 2.6%), followed by Hepatozoon canis and E. canis (each with a prevalence of 2.57 ± 2.2%). Hepatozoon canis was also diagnosed in all three of the analyzed foxes. Analysis of yearly prevalence showed that tick-borne pathogens were less frequent in raccoon in 2015, a dry and warm year compared both to 2014 and 2016. These data suggest that fecal PCR assays are unsuitable for detection of DNA of non-erythrocytic pathogens. Furthermore, they demonstrate that the raccoon (an invasive species often living in proximity to domestic areas) and the red fox are putative reservoirs for pathogenic organisms in the Community of Madrid.

  6. First phylogenetic analysis of Ehrlichia canis in dogs and ticks from Mexico. Preliminary study

    Directory of Open Access Journals (Sweden)

    Carolina G. Sosa-Gutiérrez

    2016-09-01

    Full Text Available Objective. Phylogenetic characterization of Ehrlichia canis in dogs naturally infected and ticks, diagnosed by PCR and sequencing of 16SrRNA gene; compare different isolates found in American countries. Materials and methods. Were collected Blood samples from 139 dogs with suggestive clinical manifestations of this disease and they were infested with ticks; part of 16SrRNA gene was sequenced and aligned, with 17 sequences reported in American countries. Two phylogenetic trees were constructed using the Maximum likelihood method, and Maximum parsimony. Results. They were positive to E. canis 25/139 (18.0% dogs and 29/139 (20.9% ticks. The clinical manifestations presented were fever, fatigue, depression and vomiting. Rhipicephalus sanguineus Dermacentor variabilis and Haemaphysalis leporis-palustris ticks were positive for E. canis. Phylogenetic analysis showed that the sequences of dogs and ticks in Mexico form a third group diverging of sequences from South America and USA. Conclusions. This is the first phylogenetic analysis of E. canis in Mexico. There are differences in the sequences of Mexico with those reported in South America and USA. This research lays the foundation for further study of genetic variability.

  7. Molecular and serological detection of Ehrlichia canis and Babesia vogeli in dogs in Colombia.

    Science.gov (United States)

    Vargas-Hernández, G; André, M R; Faria, J L M; Munhoz, T D; Hernandez-Rodriguez, M; Machado, R Z; Tinucci-Costa, M

    2012-05-25

    Ehrlichiosis and babesiosis are tick-borne diseases, caused mainly by Ehrlichia canis and Babesia canis, respectively, with a worldwide occurrence in dogs, whose main vector is the brown-dog tick, Rhipicephalus sanguineus. The present work aimed to detect the presence of E. canis and Babesia sp. in 91 dog blood samples in Colombia, by molecular and serological techniques. We also performed sequence alignment to indicate the identity of the parasite species infecting these animals. The present work shows the first molecular detection of E. canis and B. vogeli in dogs from Colombia. Immunoglobulin-G (IgG) antibodies to E. canis and Babesia vogeli were found in 75 (82.4%) and 47 (51.6%) sampled dogs, respectively. Thirty-seven (40.6%) and 5 (5.5%) dogs were positive in PCR for E. canis and Babesia sp., respectively. After sequencing, amplicons showed 99% of identity with isolates of E. canis and B. vogeli. The phylogenetic trees based on 16S rRNA-Anaplasmataceae sequences and 18S rRNA-piroplasmid sequences supported the identity of the found E. canis and B. vogeli DNAs, respectively. The present work shows the first molecular detection of E. canis and B. vogeli in dogs in Colombia. Copyright © 2011 Elsevier B.V. All rights reserved.

  8. The genome of obligately intracellular Ehrlichia canis revealsthemes of complex membrane structure and immune evasion strategies

    Energy Technology Data Exchange (ETDEWEB)

    Mavromatis, K.; Kuyler Doyle, C.; Lykidis, A.; Ivanova, N.; Francino, P.; Chain, P.; Shin, M.; Malfatti, S.; Larimer, F.; Copeland,A.; Detter, J.C.; Land, M.; Richardson, P.M.; Yu, X.J.; Walker, D.H.; McBride, J.W.; Kyrpides, N.C.

    2005-09-01

    Ehrlichia canis, a small obligately intracellular, tick-transmitted, gram-negative, a-proteobacterium is the primary etiologic agent of globally distributed canine monocytic ehrlichiosis. Complete genome sequencing revealed that the E. canis genome consists of a single circular chromosome of 1,315,030 bp predicted to encode 925 proteins, 40 stable RNA species, and 17 putative pseudogenes, and a substantial proportion of non-coding sequence (27 percent). Interesting genome features include a large set of proteins with transmembrane helices and/or signal sequences, and a unique serine-threonine bias associated with the potential for O-glycosylation that was prominent in proteins associated with pathogen-host interactions. Furthermore, two paralogous protein families associated with immune evasion were identified, one of which contains poly G:C tracts, suggesting that they may play a role in phase variation and facilitation of persistent infections. Proteins associated with pathogen-host interactions were identified including a small group of proteins (12) with tandem repeats and another with eukaryotic-like ankyrin domains (7).

  9. An antigen shared by human granulocytes, monocytes, marrow granulocyte precursors and leukemic blasts.

    Science.gov (United States)

    Shumak, K H; Rachkewich, R A

    1983-01-01

    An antibody to human granulocytes was raised in rabbits by immunization with granulocytes pretreated with rabbit antibody to contaminating antigens. The antibody reacted not only with granulocytes but also with monocytes and bone marrow granulocyte precursors including colony-forming units in culture (CFU-C). In tests with leukemic cells, the antibody reacted with blasts from most (8 of 9) patients with acute myelomonoblastic leukemia and from some patients with acute myeloblastic leukemia, morphologically undifferentiated acute leukemia and chronic myelogenous leukemia in blast crisis. The antibody did not react with blasts from patients with acute lymphoblastic leukemia nor with leukemic cells from patients with chronic lymphocytic leukemia.

  10. Radioassay of granulocyte chemotaxis. Studies of human granulocytes and chemotactic factors. [/sup 51/Cr tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Gallin, J I

    1974-01-01

    The above studies demonstrate that the /sup 51/Cr radiolabel chemotactic assay is a relatively simple and objective means for studying leukocyte chemotaxis in both normal and pathological conditions. Application of this method to studies of normal human chemotaxis revealed a relatively narrow range of normal and little day-to-day variability. Analysis of this variability revealed that there is more variability among the response of different granulocytes to a constant chemotactic stimulus than among the chemotactic activity of different sera to a single cell source. Utilizing the /sup 51/Cr radioassay, the abnormal granulocyte chemotactic behavior reported in Chediak-Higashi syndrome and a patient with recurrent pyogenic infections and mucocutaneous candidiasis has been confirmed. The /sup 51/Cr chemotactic assay has also been used to assess the generation of chemotactic activity from human serum and plasma. The in vitro generation of two distinct chemotactic factors were examined; the complement product (C5a) and kallikrein, an enzyme of the kinin-generating pathway. Kinetic analysis of complement-related chemotactic factor formation, utilizing immune complexes or endotoxin to activate normal sera in the presence or absence of EGTA as well as kinetic analysis of activation of C2-deficient human serum, provided an easy means of distinguishing the classical (antibody-mediated) complement pathway from the alternate pathway. Such kinetic analysis is necessary to detect clinically important abnormalities since, after 60 min of generation time, normal chemotactic activity may be present despite complete absence or inhibition of one complement pathway. The chemotactic factor generated by either pathway of complement activation appears to be predominately attributable to C5a.

  11. Congenital hypogammaglobulinemia associated with granulocyte disorders. A case presentation

    International Nuclear Information System (INIS)

    Sanchez Segura, Miriam C; Marsan Suarez, Vianed; Socarras Ferrer, Bertha B; Ojeda de Leon, Norma

    2009-01-01

    This is the case of a child aged 11 months with a history of systemic sepsis from Pseudomona aeruginosa at 5 months, neutropenia, leucopenia, sepsis-associated anemia and from then, recurrent acute respiratory infections of the high respiratory tract, allergic manifestations and furunculosis from pseudomona. Immunologic study conducted showed a decreased figure of IgG with a light increase of CD4 +c ooperative-IgM of T cells. Also, we found the presence of neutropenia and marked defect of phagocytosis. We made the diagnosis of granulocyte-associate congenital hypogammaglobulinemia. The patient was treated with human gamma globulin by intramuscular route, transference factor and immunoferon, with an obvious improvement

  12. Natural history of zoonotic Ehrlichia species in the United States and discovery of a novel ehrlichial pathogen

    NARCIS (Netherlands)

    Loftis, A.D.

    2008-01-01

    Ehrlichia are obligate intracellular pathogens, transmitted by ixodid ticks, of both animals and humans. Ehrlichiae are emerging diseases in the USA, and the discovery of new species proceeds more rapidly than the development of models to study these agents. Laboratory animals were evaluated as

  13. Associated Factors to Seroprevalence of Ehrlichia spp. in Dogs of Quintana Roo, Mexico.

    Science.gov (United States)

    Martínez-Vega, Pedro Pablo; Bolio-Gonzalez, Manuel Emilio; Rodríguez-Vivas, Roger Iván; Gutierrez-Blanco, Eduardo; Pérez-Osorio, Carlos; Villegas-Perez, Sandra Luz; Sauri-Arceo, Carlos Humberto

    2016-01-01

    The objective of this study was to determine the seroprevalence to Ehrlichia spp. in dogs from Xcalak, Quintana Roo, Mexico, and the associated factors. Serum samples were obtained from 118 dogs and used in an indirect immunofluorescent assay test for the detection of antibodies against Ehrlichia spp. A questionnaire was used to obtain information about possible variables associated with seroprevalence. These variables were analyzed through Chi 2 test and logistic regression. Dog seroprevalence of antibodies against Ehrlichia spp. was 64% (75/118). Fifty-two percent (61/118) of dogs had tick infestation which was identified as Rhipicephalus sanguineus sensu lato . Anemia was observed in 36% of dogs. Leucopenia (2.5%), thrombocytopenia (70%), and hemorrhage (14%) were also observed. Thirty-one percent (23/75) of dogs with anemia, 4% (3/75) of dogs with leucopenia, 80% (60/75) of dogs with thrombocytopenia, 17% (13/75) of dogs with hemorrhages, and 59% (44/75) of dogs with ticks were positive for Ehrlichia spp. antibodies. The factors associated with seroprevalence were age (1-3 and >3 years old, OR = 7.77 and OR = 15.39, resp.), tick infestation (OR = 3.13), and thrombocytopenia (OR = 3.36). In conclusion, seroprevalence of Ehrlichia spp. was high in the community of Xcalak and its associated factors were age, tick infestation, and thrombocytopenia.

  14. Associated Factors to Seroprevalence of Ehrlichia spp. in Dogs of Quintana Roo, Mexico

    Directory of Open Access Journals (Sweden)

    Pedro Pablo Martínez-Vega

    2016-01-01

    Full Text Available The objective of this study was to determine the seroprevalence to Ehrlichia spp. in dogs from Xcalak, Quintana Roo, Mexico, and the associated factors. Serum samples were obtained from 118 dogs and used in an indirect immunofluorescent assay test for the detection of antibodies against Ehrlichia spp. A questionnaire was used to obtain information about possible variables associated with seroprevalence. These variables were analyzed through Chi2 test and logistic regression. Dog seroprevalence of antibodies against Ehrlichia spp. was 64% (75/118. Fifty-two percent (61/118 of dogs had tick infestation which was identified as Rhipicephalus sanguineus sensu lato. Anemia was observed in 36% of dogs. Leucopenia (2.5%, thrombocytopenia (70%, and hemorrhage (14% were also observed. Thirty-one percent (23/75 of dogs with anemia, 4% (3/75 of dogs with leucopenia, 80% (60/75 of dogs with thrombocytopenia, 17% (13/75 of dogs with hemorrhages, and 59% (44/75 of dogs with ticks were positive for Ehrlichia spp. antibodies. The factors associated with seroprevalence were age (1–3 and >3 years old, OR = 7.77 and OR = 15.39, resp., tick infestation (OR = 3.13, and thrombocytopenia (OR = 3.36. In conclusion, seroprevalence of Ehrlichia spp. was high in the community of Xcalak and its associated factors were age, tick infestation, and thrombocytopenia.

  15. Molecular epidemiology of Anaplasma platys, Ehrlichia canis and Babesia vogeli in stray dogs in Paraná, Brazil

    Directory of Open Access Journals (Sweden)

    Claudia M. Ribeiro

    Full Text Available ABSTRACT: Hemoparasitic infections are tick-borne diseases, which affect animals and humans. Considering the importance of canine hemoparasitic infections in veterinary clinics, this study aimed to determine the occurrence of Anaplasma platys, Ehrlichia canis and Babesia vogeli in blood samples from 182 dogs not domiciled in the city of Pato Branco, southwestern region of Paraná State, Brazil, using polymerase chain reaction (PCR. The prevalence of A. platys and B. vogeli was 32.9% and 10.9% respectively, and A. platys infection prevailed (p<0.001. The number of dogs positive for A. platys was larger in Winter (p<0.05. All blood samples were negative for E. canis. In the dogs, infestation by Amblyomma cajennense predominated over that by Rhipicephalus sanguineus (p<0.001; but there was no significant association between PCR and the variables presence of ticks, sex and age. Dogs infected by A. platys and B. vogeli showed thrombocytopenia, lymphopenia and leukocytosis; but there was no correlation between such hematological changes and infection by hemoparasites. This appears to be the first molecular study that demonstrates the existence of A. platys and B. vogeli in dogs from the southwestern region of Paraná.

  16. Comparison of Ehrlichia muris strains isolated from wild mice and ticks and serologic survey of humans and animals with E. muris as antigen.

    Science.gov (United States)

    Kawahara, M; Ito, T; Suto, C; Shibata, S; Rikihisa, Y; Hata, K; Hirai, K

    1999-04-01

    In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had been isolated. These new isolates were compared with the E. muris type strain. The mouse virulence and ultrastructure of the new isolates were similar to those of the type strain, and all of them were cross-reactive with each other, as well as with the type strain, by indirect immunofluorescent-antibody test. The levels of similarity of the base sequences of the 16S rRNA gene of one of the A. speciosus isolates and one of the tick isolates to that of the E. muris type strain were 99.79 and 99.93%, respectively. We suggest that all of these isolates are E. muris; that E. muris is not limited to Eothenomys kageus but infects other species of mice; and that E. muris is present at locations other than Aichi Prefecture. It appears that H. flava is a potential vector of E. muris. Twenty (1%) of 1803 humans from metropolitan Tokyo were found to be seropositive for E. muris antibodies. A serological survey revealed that exposure to E. muris or organisms antigenically cross-reactive to E. muris occurred among dogs, wild mice, monkeys, bears, deer, and wild boars in Gifu Prefecture, nearby prefectures, and Nagoya City, central Japan. However, human beings and Rattus norvegicus rats in this area were seronegative. These results indicate broader geographic distribution of and human and animal species exposure to E. muris or related Ehrlichia spp. in Japan.

  17. Molecular detection of Ehrlichia canis, Hepatozoon canis and Babesia canis vogeli in stray dogs in Mahasarakham province, Thailand.

    Science.gov (United States)

    Piratae, Supawadee; Pimpjong, Kiattisak; Vaisusuk, Kotchaphon; Chatan, Wasupon

    2015-01-01

    Canine tick borne diseases showing distribution worldwide have caused morbidity and mortality in dogs. This study observed the mainly tick borne pathogens described for dogs in Thailand, Ehrlichia canis, Hepatozoon canis and Babesia canis vogeli. From May to July 2014, blood samples were collected from 79 stray dogs from 7 districts of Mahasarakham province to molecular surveyed for 16s rRNA gene of E. canis and 18s rRNA gene of H. canis and B. canis vogeli. Twenty eight (35.44%) of stray dogs showed the infection with tick borne pathogens. The prevalence of E. canis infection was the highest with 21.5% (17/79). DNA of H. canis and B. canis vogeli were detected at the prevalence of 10.1% (8/79) and 6.3% (5/79), respectively. Co-infection between E. canis and B. canis vogeli were identified in 2 (2.5%) dogs. The results indicated that a wide range of tick borne pathogens are circulation in the canine population in Mahasarakham province. This study is the first report on prevalence of E. canis, H. canis and B. canis vogeli in stray dogs in Mahasarakham, a province in northern part of Thailand. This data providing is important to understand the prevalence of E. canis, H. canis and B. canis vogeli infection in stray dogs in this region, which will assist in the management of these blood parasite.

  18. Granulocyte-mobilized bone marrow.

    Science.gov (United States)

    Arcese, William; De Angelis, Gottardo; Cerretti, Raffaella

    2012-11-01

    In the last few years, mobilized peripheral blood has overcome bone marrow as a graft source, but, despite the evidence of a more rapid engraftment, the incidence of chronic graft-versus-host disease is significantly higher with, consequently, more transplant-related mortality on the long follow-up. Overall, the posttransplant outcome of mobilized peripheral blood recipients is similar to that of patients who are bone marrow grafted. More recently, the use of bone marrow after granulocyte colony-stimulating factor (G-CSF) donor priming has been introduced in the transplant practice. Herein, we review biological acquisitions and clinical results on the use of G-CSF-primed bone marrow as a source of hematopoietic stem cells (HSC) for allogeneic stem cell transplantation. G-CSF the increases the HSC compartment and exerts an intense immunoregulatory effect on marrow T-cells resulting in the shift from Th1 to Th2 phenotype with higher production of anti-inflammatory cytokines. The potential advantages of these biological effects have been translated in the clinical practice by using G-CSF primed unmanipulated bone marrow in the setting of transplant from human leukocyte antigen (HLA)-haploidentical donor with highly encouraging results. For patients lacking an HLA-identical sibling, the transplant of G-CSF primed unmanipulated bone marrow from a haploidentical donor combined with an intense in-vivo immunosuppression is a valid alternative achieving results that are well comparable with those reported for umbilical cord blood, HLA-matched unrelated peripheral blood/bone marrow or T-cell-depleted haploidentical transplant.

  19. Radiation Effects on Granulocyte Formation and Maturation in Various Species and at Different Levels of Exposure

    Energy Technology Data Exchange (ETDEWEB)

    Fliedner, T. M. [Forschungsgruppe Freiburg, Institut fuer Haematologie der Gesellschaft fuer Strahlenforschung Assoziation mit EURATOM, Freiburg/Breisgau, Federal Republic of Germany (Germany)

    1967-07-15

    Granulocytopenia is one of the well-known consequences of radiation exposure of all or part of the body. It is of concern to the clinician who has to deal with the possible manifestation of bacterial infection that is associated with its development. For the investigator, the time course and pattern of granulocyte changes in the peripheral blood and of their precursors in the bone marrow after radiation may serve to indicate the response of a cell renewal system in general, since its internal structure with a stem-cell pool, a proliferating pool,, a maturation pool and a functioned pool appears to be the same in many other cell renewal systems. Since several of the time parameters of the granulocytic cell renewal system are known as well as the consequences of whole-body irradiation on this system for several species, it may be of interest to this Panel to analyse the radiation effects on granulocytopoiesis. This problem has been the concern of several previous reviews. It is the purpose of this paper to study the following aspects: (a) pattern of development of granulocytopenia as a function of exposure level and of species, (b) comparison of granulocyte maturation in different species as a basis for the analysis of granulocyte depression, and (c) appearance and disappearance of granulocytes with mitotically connected abnormalities as a possible indicator of radiation effects on the proliferative pool.

  20. The use of technetium-99m hexamethylpropylene amine oxime labelled granulocytes with single-photon emission tomography imaging in the detection and follow-up of recurrence of infective endocarditis complicating transvenous endocardial pacemaker

    International Nuclear Information System (INIS)

    Ramackers, J.M.; Kotzki, P.O.; Couret, I.; Messner-Pellenc, P.; Davy, J.M.; Rossi, M.

    1995-01-01

    In this case report we present a patient with a recurrence of subacute bacterial infectious endocarditis (IE) complicating a transvenous endocardial pacemaker. Technetium-99m hexamethylpropylene amine oxime ( 99m Tc-HMPAO) labelled granulocytes were used for diagnosis and follow-up under medical treatment only, since surgical removal of the pacemaker lead was ruled out because of the general condition of the patient. Single-photon emission tomography (SPET) imaging displayed the active lesion previously suspected on echography. At the end of antibiotic therapy, SPET indicated a favourable disease outcome whereas echocardiographic abnormalities remained nearly unchanged. The medical treatment had eradicated the IE, and the patient did well for more than 1 year thereafter. (orig.)

  1. The use of technetium-99m hexamethylpropylene amine oxime labelled granulocytes with single-photon emission tomography imaging in the detection and follow-up of recurrence of infective endocarditis complicating transvenous endocardial pacemaker

    Energy Technology Data Exchange (ETDEWEB)

    Ramackers, J M [Department of Nuclear Medicine, CHU E. Herriot, Lyon (France); Kotzki, P O [Department of Nuclear Medicine, CHU Lapeyronie et A. de Villeneuve, Montpellier (France); Couret, I [Department of Nuclear Medicine, CHU Lapeyronie et A. de Villeneuve, Montpellier (France); Messner-Pellenc, P [Department of Cardiology, CHU Lapeyronie et A. Villeneuve, Montpellier (France); Davy, J M [Department of Cardiology, CHU Lapeyronie et A. Villeneuve, Montpellier (France); Rossi, M [Department of Nuclear Medicine, CHU Lapeyronie et A. de Villeneuve, Montpellier (France)

    1995-11-01

    In this case report we present a patient with a recurrence of subacute bacterial infectious endocarditis (IE) complicating a transvenous endocardial pacemaker. Technetium-99m hexamethylpropylene amine oxime ({sup 99m}Tc-HMPAO) labelled granulocytes were used for diagnosis and follow-up under medical treatment only, since surgical removal of the pacemaker lead was ruled out because of the general condition of the patient. Single-photon emission tomography (SPET) imaging displayed the active lesion previously suspected on echography. At the end of antibiotic therapy, SPET indicated a favourable disease outcome whereas echocardiographic abnormalities remained nearly unchanged. The medical treatment had eradicated the IE, and the patient did well for more than 1 year thereafter. (orig.)

  2. Periodic Granulocyte Count Measuring Is Useful for Detecting Asymptomatic Agranulocytosis in Antithyroid Drug-Treated Patients with Graves' Disease.

    Science.gov (United States)

    Nakamura, Hirotoshi; Ide, Akane; Kudo, Takumi; Nishihara, Eijun; Ito, Mitsuru; Miyauchi, Akira

    2016-12-01

    Finding agranulocytosis (AG) at an early stage is important to improve outcome, but periodic granulocyte count monitoring is not generally recommended for patients with Graves' disease, because AG develops suddenly. At the Kuma Hospital, Graves' patients under antithyroid drug (ATD) treatment in an outpatient clinic have a granulocyte count examination during each visit, and if it is Graves' disease were 131 I-radioisotope therapy (19 patients), thyroidectomy (2 patients), inorganic iodine (1 patient), or another ATD (1 patient). Among the 33 GP patients, 31 (94%), including 20 asymptomatic cases, were discovered during periodic granulocyte count monitoring. Most of them stopped ATD, and other treatments for Graves' disease were selected. Periodic monitoring of granulocyte counts is useful for identifying AG and GP patients with no or minimum infection symptoms.

  3. Peptide Nucleic Acid Knockdown and Intra-host Cell Complementation of Ehrlichia Type IV Secretion System Effector

    Directory of Open Access Journals (Sweden)

    Pratibha Sharma

    2017-06-01

    Full Text Available Survival of Ehrlichia chaffeensis depends on obligatory intracellular infection. One of the barriers to E. chaffeensis research progress has been the inability, using conventional techniques, to generate knock-out mutants for genes essential for intracellular infection. This study examined the use of Peptide Nucleic Acids (PNAs technology to interrupt type IV secretion system (T4SS effector protein expression in E. chaffeensis followed by intracellular complementation of the effector to determine its requirement for infection. Successful E. chaffeensis infection depends on the E. chaffeensis-specific T4SS protein effector, ehrlichial translocated factor-1 (Etf-1, which induces Rab5-regulated autophagy to provide host cytosolic nutrients required for E. chaffeensis proliferation. Etf-1 is also imported by host cell mitochondria where it inhibits host cell apoptosis to prolong its infection. We designed a PNA specific to Etf-1 and showed that the PNA bound to the target region of single-stranded Etf-1 RNA using a competitive binding assay. Electroporation of E. chaffeensis with this PNA significantly reduced Etf-1 mRNA and protein, and the bacteria's ability to induce host cell autophagy and infect host cells. Etf-1 PNA-mediated inhibition of ehrlichial Etf-1 expression and E. chaffeensis infection could be intracellularly trans-complemented by ectopic expression of Etf-1-GFP in host cells. These data affirmed the critical role of bacterial T4SS effector in host cell autophagy and E. chaffeensis infection, and demonstrated the use of PNA to analyze the gene functions of obligate intracellular bacteria.

  4. Hemopathologic consequences of protracted gamma irradiation: alterations in granulocyte reserves and granulocyte mobilization

    International Nuclear Information System (INIS)

    Seed, T.M.; Cullen, S.M.; Kaspar, L.V.; Tolle, D.V.; Fritz, T.E.

    1980-01-01

    Aplastic anemia and myelogenous leukemia are prominent pathologic effects in beagles exposed to continuous, daily, low-dose gamma irradiation. In the present work, granulocyte reserves and related mobilization functions have been sequentially assessed by the endotoxin stress assay during the preclinical and clinical phases of these hemopoietic disorders. Characteristic patterns of granulocyte reserve mobilization are described that reflect given stages of pathologic progression. For radiation-induced leukemia, a five-stage pattern has been proposed. In contrast, a simple pattern of progressive, time-dependent contraction of granulocyte reserves and mobilization capacity was noted in the development of terminal aplastic anemia. Early preclinical phases of radiation-induced leukemia appear to involve an extensive depletion of the granulocyte reserves (phase I) during the first approx. 200 days of exposure followed by a partial renewal of the reserves and associated mobilization functions between approx. 200 and 400 days (phase II). Sustained, subnormal granulocyte mobilizations (phase III) following endotoxin stress typify the responses of dogs during the intermediate phase, whereas late preclinical, preleukemic stages (phase IV) are characterized by a further expansion of the reserves and in the mobilization capacities, particularly of the less mature granulocytes. Such late alterations in the pattern of granulocyte mobilization, together with other noted cellular aberrancies in the peripheral blood and marrow, appear to indicate leukemia (phase V) onset

  5. Molecular detection of Dirofilaria immitis, Hepatozoon canis, Babesia spp., Anaplasma platys and Ehrlichia canis in dogs on Costa Rica.

    Science.gov (United States)

    Wei, Lanjing; Kelly, Patrick; Ackerson, Kate; El-Mahallawy, Heba S; Kaltenboeck, Bernhard; Wang, Chengming

    2014-03-01

    Although vector-borne diseases are important causes of morbidity and mortality in dogs in tropical areas, there is little information on these conditions in Costa Rica. In PCRs of blood from dogs in Costa Rica, we did not detect DNAs of Rickettsia (R.) felis and Coxiella (C.) burnetii but we did find evidence of infection with Dirofilaria (D.) immitis (9/40, 22.5%), Hepatozoon (H.) canis (15/40, 37.5%), Babesia spp. (10/40, 25%; 2 with B. gibsoni and 8 with B. vogeli), Anaplasma (A.) platys (3/40, 7.5%) and Ehrlichia (E.) canis (20/40, 50%). Nine dogs (22.5%) were free of any vector-borne pathogens while 14 (35%) were infected with a single pathogen, 11 (27.5%) with two, 4 (10%) with three, 1 (2.5%) with four, and 1 (2.5%) with five pathogens. Dogs in Costa Rica are commonly infected with vector-borne agents.

  6. The redistribution of granulocytes following E. coli endotoxin induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Lillevang, S T; Tønnesen, Else Kirstine

    1994-01-01

    Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes...

  7. The recombinant 120-kilodalton protein of Ehrlichia chaffeensis, a potential diagnostic tool.

    OpenAIRE

    Yu, X J; Crocquet-Valdes, P; Cullman, L C; Walker, D H

    1996-01-01

    DNA encoding two repeat units of 120-kDa protein of Ehrlichia chaffeensis was cloned into the expression vector pGEX and expressed in Escherichia coli. The sensitivity and specificity of a dot blot assay for detection of human antibodies with the recombinant protein were 86 and 100%, respectively, compared with an indirect immunofluorescence assay.

  8. Detection of Ehrlichia canis in domestic cats in the central-western region of Brazil

    Directory of Open Access Journals (Sweden)

    Ísis Assis Braga

    2014-06-01

    Full Text Available Ehrlichiosis is a worldwide distributed disease caused by different bacteria of the Ehrlichia genus that are transmitted by arthropod vectors. Its occurrence in dogs is considered endemic in several regions of Brazil. Regarding cats, however, few studies have been done and, consequently, there is not enough data available. In order to detect Ehrlichia spp. in cats from the central-western region of Brazil, blood and serum samples were collected from a regional population of 212 individuals originated from the cities of Cuiabá and Várzea Grande. These animals were tested by the Immunofluorescence Assay (IFA and the Polymerase Chain Reaction (PCR designed to amplify a 409 bp fragment of the dsb gene. The results obtained show that 88 (41.5% cats were seropositive by IFA and 20 (9.4% cats were positive by PCR. The partial DNA sequence obtained from PCR products yielded twenty samples that were found to match perfectly the Ehrlichia canis sequences deposited on GenBank. The natural transmission of Ehrlichia in cats has not been fully established. Furthermore, tick infestation was not observed in the evaluated cats and was not observed any association between age, gender and positivity of cats in both tests. The present study reports the first serological and molecular detection of E. canis in domestic cats located in the endemic area previously mentioned.

  9. Ehrlichia canis and Anaplasma platys in ticks of dogs in Cuiaba, Mato GrossoEhrlichia canis e Anaplasma platys em carrapatos de cães de Cuiabá, Mato Grosso

    Directory of Open Access Journals (Sweden)

    Valéria Dutra

    2012-06-01

    Full Text Available Diseases transmitted by arthropods such as Rhipicephalus sanguineus, are caused by a spectrum of pathogens. Among these are the canine monocytic ehrlichiosis and cyclical thrombocytopenia with a cosmopolitan distribution. Aiming to verify the presence of DNA of Anaplasma platys and Ehrlichia canis in ticks R. sanguineus collected in the period 2008 to 2009 of 380 infected dogs. Ticks, after maceration, were subjected to DNA extraction and then nested PCR was performed for amplification of A. platys and E. canis. Of these, 81 (29.7% amplified DNA from ehrlichiais agents, where 38 (17.9% amplified in E. canis and 32 (15.7% for A. platys. The observation of two pathogens, combined with worldwide distribution of the tick R. sanguineus, demonstrates the high risk of infection with these pathogens in dogs in the city of Cuiaba. Doenças transmitidas por artrópodes, como o Rhipicephalus sanguineus, são causadas por um espectro de patógenos. Dentre estas, estão a erliquiose monocítica canina e trombocitopenia cíclica com distribuição cosmopolita. Com o objetivo de verificar a presença de DNA de Anaplasma platys e Ehrlichia canis em carrapatos R. sanguineus coletados no período de 2008 a 2009 de 380 cães infestados. Os carrapatos, após a maceração, foram submetidos a extração de DNA e, em seguida, foi realizada a Nested PCR para a amplificação da espécie A. platys e E. canis. Destes, 81 (29.7% amplificaram o DNA dos agentes ehrlichiais, onde 38 (17.9% amplificaram para E. canis e 32 (15.7% para A. platys. A observação dos dois patógenos, combinado com distribuição mundial do carrapato R. sanguineus, demonstra o elevado risco de infecção por esses patógenos de cães na cidade de Cuiabá.

  10. Quantification of deposition of neutrophilic granulocytes on vascular grafts in dogs with 111In-labeled granulocytes

    International Nuclear Information System (INIS)

    Dewanjee, M.K.; Solis, E.; Mackey, S.T.; Socher, S.; Chowdhury, S.; Wu, F.P.; Kaye, M.P.

    1985-01-01

    A new radioisotopic technique has been developed for quantification of deposition of neutrophilic granulocytes on vascular grafts. Nine healthy mongrel dogs underwent bilateral femoral artery resection and reconstruction with grafts of the femoral vein and Gore-Tex. Pure granulocytes that had been separated from whole blood by centrifugal elutriation were labeled with 111 In-tropolone in plasma. The granulocyte harvesting efficiency was 25 +/- 12%, and the labeling efficiency was 87 +/- 7%. Three hours after injection of labeled granulocytes and 2 hours after reperfusion, the grafts were harvested and cut into several segments for study of areas of anastomoses and midsections. On the basis of the radioactivity in the blood and in anastomotic and graft sections, the area of graft sections, and the neutrophilic granulocyte and differential leukocyte counts, the number of neutrophilic granulocytes adherent to a unit area and the total number of neutrophilic granulocytes on graft sections were calculated. These quantifications of the deposition of neutrophilic granulocytes indicated that the midsections of Gore-Tex grafts retained more neutrophilic granulocytes than did the midsections of vein grafts. Although the anastomotic areas retained more neutrophilic granulocytes than did the midsections of vein grafts, the opposite finding prevailed for the Gore-Tex grafts. A major fraction of neutrophilic granulocytes on Gore-Tex grafts was incorporated into the thrombus. Semiquantitative information obtained by scintigraphy of the deposition of neutrophilic granulocytes on vascular grafts also confirmed this observation

  11. Effect of granulocyte-colony stimulating factor on empiric therapy with flomoxef sodium and tobramycin in febrile neutropenic patients with hematological malignancies. Kan-etsu Hematological Disease and Infection Study Group.

    Science.gov (United States)

    Yoshida, M; Karasawa, M; Naruse, T; Fukuda, M; Hirashima, K; Oh, H; Ninomiya, H; Abe, T; Saito, K; Shishido, H; Moriyama, Y; Shibata, A; Motoyoshi, K; Nagata, N; Miura, Y

    1999-02-01

    The clinical effects of concomitant use of granulocyte-colony stimulating factor (G-CSF) on empiric antibiotic therapy in febrile neutropenic patients were evaluated in a randomized fashion. Two hundred and fourteen neutropenic febrile episodes (neutrophil counts flomoxef sodium and tobramycin with or without G-CSF. The resolution of fever at day 4 (excellent response) or at day 7 (good response) was deemed effective. Among 157 evaluable episodes, the observed excellent responses were 31 (38.8%) and the good responses were 20 (25.0%) in the G-CSF group; those in the control group were 26 (33.8%) and 25 (32.5%), respectively. The overall efficacy rate was 63.8% (51/80) in the G-CSF group and 66.2% (51/77) in the control group (not significant). The initial neutrophil count was 0.186 +/- 0.249 x 10(9)/l in the G-CSF group and 0.235 +/- 0.290 x 10(9)/l in the control group, and rose to 2.889 +/- 4.198 x 10(9)/l and 0.522 +/- 0.844 x 10(9)/l, respectively, at day 7. These results indicate that G-CSF does not affect the rate of response to empiric antibiotic therapy in febrile neutropenic patients, although a significant effect of G-CSF was observed on neutrophil recovery.

  12. The glycoprotein TRP36 of Ehrlichia sp. UFMG-EV and related cattle pathogen Ehrlichia sp. UFMT-BV evolved from a highly variable clade of E. canis under adaptive diversifying selection

    Czech Academy of Sciences Publication Activity Database

    Cabezas-Cruz, A.; Valdés, James J.; de la Fuente, J.

    2014-01-01

    Roč. 7, DEC 10 2014 (2014), s. 584 ISSN 1756-3305 R&D Projects: GA MŠk(CZ) EE2.3.30.0032 Institutional support: RVO:60077344 Keywords : Ehrlichia sp. UFMG-EV * Ehrlichia sp. UFMT-BV * E. mineirensis * Host-shift * Diversifying episodic selection Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.430, year: 2014

  13. Detection and phylogenetic characterisation of novel Anaplasma and Ehrlichia species in Amblyomma triguttatum subsp. from four allopatric populations in Australia.

    Science.gov (United States)

    Gofton, Alexander W; Waudby, Helen P; Petit, Sophie; Greay, Telleasha L; Ryan, Una M; Irwin, Peter J

    2017-08-01

    Anaplasma and Ehrlichia spp. are tick-borne pathogens that can cause severe disease in domestic animals, and several species are responsible for emerging zoonoses in the northern hemisphere. Until recently, the only members of these genera reported in Australia (A. marginale, A. centrale, and A. platys) were introduced from other continents, through the importation of domestic animals and their associated ticks. However, unique Anaplasma and Ehrlichia 16S rRNA gene sequences were recently detected for the first time in native Australian ticks, particularly in Amblyomma triguttatum subsp. ticks from southwest Western Australia (WA). We used molecular techniques to survey Am. triguttatum subsp. ticks from four allopatric populations in southern and western Australia for Anaplasma and Ehrlichia species, and described here the phylogeny of these novel organisms. An A. bovis variant (genotype Y11) was detected in ticks from two study sites; Yanchep National Park (12/280, 4.3%) and Barrow Island (1/69, 1.4%). Phylogenetic analysis of 16S rRNA and groEL gene sequences concluded that A. bovis genotype Y11 is a unique genetic variant, distinct from other A. bovis isolates worldwide. Additionally, a novel Ehrlichia species was detected in Am. triguttatum subsp. from three of the four study sites; Yanchep National Park (18/280, 6.4%), Bungendore Park (8/46, 17.4%), and Innes National Park (9/214, 4.2%), but not from Barrow Island. Phylogenetic analysis of 16S, groEL, gltA, and map1 gene sequences revealed that this Ehrlichia sp. is most closely related to, but clearly distinct from, E. ruminantium and Ehrlichia sp. Panola Mountain. We propose to designate this new species 'Candidatus Ehrlichia occidentalis'. Anaplasma bovis genotype Y11 and 'Candidatus E. occidentalis' are the first Anaplasma and Ehrlichia species to be recorded in native Australian ticks. Copyright © 2017 Elsevier GmbH. All rights reserved.

  14. Ehrlichia secretes Etf-1 to induce autophagy and capture nutrients for its growth through RAB5 and class III phosphatidylinositol 3-kinase.

    Science.gov (United States)

    Lin, Mingqun; Liu, Hongyan; Xiong, Qingming; Niu, Hua; Cheng, Zhihui; Yamamoto, Akitsugu; Rikihisa, Yasuko

    2016-11-01

    Ehrlichia chaffeensis is an obligatory intracellular bacterium that causes a potentially fatal emerging zoonosis, human monocytic ehrlichiosis. E. chaffeensis has a limited capacity for biosynthesis and metabolism and thus depends mostly on host-synthesized nutrients for growth. Although the host cell cytoplasm is rich with these nutrients, as E. chaffeensis is confined within the early endosome-like membrane-bound compartment, only host nutrients that enter the compartment can be used by this bacterium. How this occurs is unknown. We found that ehrlichial replication depended on autophagy induction involving class III phosphatidylinositol 3-kinase (PtdIns3K) activity, BECN1 (Beclin 1), and ATG5 (autophagy-related 5). Ehrlichia acquired host cell preincorporated amino acids in a class III PtdIns3K-dependent manner and ehrlichial growth was enhanced by treatment with rapamycin, an autophagy inducer. Moreover, ATG5 and RAB5A/B/C were routed to ehrlichial inclusions. RAB5A/B/C siRNA knockdown, or overexpression of a RAB5-specific GTPase-activating protein or dominant-negative RAB5A inhibited ehrlichial infection, indicating the critical role of GTP-bound RAB5 during infection. Both native and ectopically expressed ehrlichial type IV secretion effector protein, Etf-1, bound RAB5 and the autophagy-initiating class III PtdIns3K complex, PIK3C3/VPS34, and BECN1, and homed to ehrlichial inclusions. Ectopically expressed Etf-1 activated class III PtdIns3K as in E. chaffeensis infection and induced autophagosome formation, cleared an aggregation-prone mutant huntingtin protein in a class III PtdIns3K-dependent manner, and enhanced ehrlichial proliferation. These data support the notion that E. chaffeensis secretes Etf-1 to induce autophagy to repurpose the host cytoplasm and capture nutrients for its growth through RAB5 and class III PtdIns3K, while avoiding autolysosomal killing.

  15. Role of opsonins in clinical response to granulocyte transfusion in granulocytopenic patients

    International Nuclear Information System (INIS)

    Keusch, G.T.; Ambinder, E.P.; Kovacs, I.; Goldberg, J.D.; Phillips, D.M.; Holland, J.F.

    1982-01-01

    Fifty febrile severely granulocytopenic patients were given four daily transfusions of 2.2 X 10(10) normal donor granulocytes. Twenty-three responded clinically, although both responders and nonresponders were similar in clinical characteristics at the outset. This study examines the relation between serum opsonic activity before initiation of granulocyte administration and clinical response. Opsonic activity to three test organisms (Escherichia coli 286 and ON 2, and Staphylococcus aureus) and to 15 blood stream isolates from 14 patients was measured as serum-dependent uptake of heat-killed 14 C-labeled bacteria by normal donor leukopheresis granulocytes in an in vitro assay and compared with results obtained with a standard normal serum in each assay. At a concentration of 8 percent serum, all patient groups were equivalent to standard for the three test organisms. When rate-limiting concentrations of serum were employed, opsonic activity remained similar to standard for S. aureus in all patient groups and for the two E. coli strains in responders. In contrast, opsonins for E. coli decreased to 41 to 50 percent of standard in nonresponders. When patients with proved infection were separately analyzed, opsonin activity for E. coli was significantly greater in responders than nonresponders. Eight of 10 patients with 75 percent or greater of standard for opsonic activity against their own blood stream isolates also responded, whereas zero of four with less than 75 percent of standard had a favorable outcome. These results indicate that serum opsonic activity may be a determinant of clinical response to granulocyte transfusion in infected granulocytopenic patients. We conclude that opsonic activity should be assessed in such patients before granulocyte administration and suggest a trial of plasma infusion in opsonin-deficient patients

  16. Molecular detection of Ehrlichia canis in dogs from the Pantanal of Mato Grosso State, Brazil Detecção molecular de Ehrlichia canis em cães do Pantanal do Mato Grosso, Brasil

    Directory of Open Access Journals (Sweden)

    Luana Gabriela Ferreira dos Santos

    Full Text Available The present study evaluated the presence of Ehrlichia DNA in the blood samples of 320 dogs from the urban and rural areas of the municipality of Poconé, Pantanal region, Mato Grosso state, by Polymerase Chain Reaction (PCR, targeting the ehrlichial dsb gene. Risk factors for infection in dogs were also evaluated. Forty-eight (15%, 95% CI: 11.4-19.5% dogs were positive: 25 (15.6%, 95% CI: 10.4-22.2% from the urban area and 23 (14.4%, 95% CI: 9.3-20.8% from the rural area (P > 0.05. Partial DNA sequence obtained from PCR products of 18 samples from the urban area and 16 samples from the rural area were 100% identical to E. canis from Brazil and the USA. This study reports the first E. canis molecular detection in dogs from the northern Pantanal region.O presente estudo avaliou a presença de DNA de Ehrlichia spp. em 320 cães das áreas urbana e rural do município de Poconé, região do Pantanal de Mato Grosso, pela PCR visando o gene dsb. Os fatores de risco para a infecção em cães também foram avaliados. Quarenta e oito (15%, IC 95%: 11,4-19,5% cães foram positivos, 25 (15,6%, IC 95%: 10,4-22,2% da área urbana e 23 (14,37%, 95% CI: 9,3-20,8% da área rural (P > 0,05. Sequências parciais de DNAs obtidos a partir de produtos da PCR de 18 amostras da área urbana e 16 da área rural foram 100% idênticas a E. canis do Brasil e EUA. Este estudo relata a primeira detecção molecular de E. canis em cães da região norte do Pantanal.

  17. Mitochondrial Fragmentation in Aspergillus fumigatus as Early Marker of Granulocyte Killing Activity

    Science.gov (United States)

    Ruf, Dominik; Brantl, Victor; Wagener, Johannes

    2018-01-01

    The host's defense against invasive mold infections relies on diverse antimicrobial activities of innate immune cells. However, studying these mechanisms in vitro is complicated by the filamentous nature of such pathogens that typically form long, branched, multinucleated and compartmentalized hyphae. Here we describe a novel method that allows for the visualization and quantification of the antifungal killing activity exerted by human granulocytes against hyphae of the opportunistic pathogen Aspergillus fumigatus. The approach relies on the distinct impact of fungal cell death on the morphology of mitochondria that were visualized with green fluorescent protein (GFP). We show that oxidative stress induces complete fragmentation of the tubular mitochondrial network which correlates with cell death of affected hyphae. Live cell microscopy revealed a similar and non-reversible disruption of the mitochondrial morphology followed by fading of fluorescence in Aspergillus hyphae that were killed by human granulocytes. Quantitative microscopic analysis of fixed samples was subsequently used to estimate the antifungal activity. By utilizing this assay, we demonstrate that lipopolysaccharides as well as human serum significantly increase the killing efficacy of the granulocytes. Our results demonstrate that evaluation of the mitochondrial morphology can be utilized to assess the fungicidal activity of granulocytes against A. fumigatus hyphae. PMID:29868488

  18. (TH) diazepam binding to human granulocytes

    Energy Technology Data Exchange (ETDEWEB)

    Bond, P.A.; Cundall, R.L.; Rolfe, B.

    1985-07-08

    (TH)-diazepam binds to sites on human granulocyte membranes, with little or no binding to platelets or lymphocytes. These (TH)-diazepam binding sites are of the peripheral type, being strongly inhibited by R05-4864 (Ki=6.23nM) but only weakly by clonazepam (Ki=14 M). Binding of (TH) diazepam at 0 is saturable, specific and stereoselective. Scatchard analysis indicates a single class of sites with Bmax of 109 +/- 17f moles per mg of protein and K/sub D/ of 3.07 +/- 0.53nM. Hill plots of saturation experiments gave straight lines with a mean Hill coefficient of 1.03 +/- 0.014. Binding is time dependent and reversible and it varies linearly with granulocyte protein concentration over the range 0.025-0.300 mg of protein. 11 references, 3 figures, 1 table.

  19. MRI of perineural extramedullary granulocytic sarcoma

    Energy Technology Data Exchange (ETDEWEB)

    Graham, A. [Rehabilitation Medicine, Hunters Moor Neurological Rehabilitation Centre, Newcastle-Upon-Tyne (United Kingdom); Hodgson, T. [Neuroradiology Dept., Royal Hallamshire Hospital, Sheffield (United Kingdom); Jacubowski, J. [Neurosurgical Dept., Royal Hallamshire Hospital, Sheffield (United Kingdom); Norfolk, D. [Haematology Department, Leeds General Infirmary, Leeds LS1 3EX (United Kingdom); Smith, C. [Pathology Dept., Royal Hallamshire Hospital, Sheffield (United Kingdom)

    2001-06-01

    Granulocytic sarcoma is an extramedullary solid tumour consisting of myelogenous leukaemic blast cells, usually seen in acute myeloid leukaemia and less commonly in patients with chronic myeloid leukaemia or myeloproliferative disorders. Blast cells have a predilection for periosteal and perineural regions and rarely precede evidence of systemic disease. We present two patients, aleukaemic on peripheral blood counts, both at presentation and during subsequent treatment. We present the MRI features of this rare but important condition. (orig.)

  20. Seroprevalence of Ehrlichia ruminantium antibodies and its associated risk factors in indigenous goats of South Africa.

    Science.gov (United States)

    Mdladla, Khanyisile; Dzomba, Edgar F; Muchadeyi, Farai C

    2016-03-01

    The present study investigated the seroprevalence of antibodies to Ehrlichia ruminantium and the associated risk factors in goats from five different farming provinces of South Africa. Sera collected from 686 goats of the commercial meat type (n=179), mohair type (n=9), non-descript indigenous goats from Eastern Cape (n=56), KwaZulu-Natal (n=209), Limpopo (n=111), North West (n=61) and Northern Cape (n=11) provinces and a feral Tankwa goat (n=50) were tested for the presence of immunoglobulin G (IgG) antibodies to antigens of E. ruminantium using the indirect fluorescent-antibody test (IFAT). Fifty two percent of these goats had ticks. The overall seroprevalence of antibodies to E. ruminantium was 64.87% (445/686) with the highest seroprevalence reported for Limpopo (95.50%) and lowest for Northern Cape (20.29%). Highest seroprevalence for antibodies to E. ruminantium was observed in goats from endemic regions (76.09%), and from smallholder production systems (89.54%). High seroprevalence was also observed in non-descript indigenous goats (85.04%), adult goat (69.62%), in does (67.46%) and goats infested with ticks (85.79%). The logistic model showed a gradient of increasing risk for commercial meat type Savanna (OR=3.681; CI=1.335-10.149) and non-descript indigenous (OR=3.466; CI=1.57-7.645) compared to Boer goats and for goats from the smallholder production system (OR=2.582; CI=1.182-5.639) and those with ticks (OR=3.587; CI=2.105-6.112). Results from this study showed that E. ruminantium infections were prevalent but were widely and unevenly distributed throughout South Africa. Findings from the study facilitate identification and mapping of risk areas for heartwater and its endeminicity in South Africa and should be taken into consideration for future disease control strategies and local goat improvement programs. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. In vitro Culture of a Novel Genotype of Ehrlichia sp from Brazil

    Czech Academy of Sciences Publication Activity Database

    Zweygarth, E.; Schol, H.; Lis, K.; Cabezas Cruz, Alejandro; Thiel, C.; Silaghi, C.; Ribeiro, M.F.B.; Passos, L.M.F.

    2013-01-01

    Roč. 60, NOV 2013 (2013), s. 86-92 ISSN 1865-1674 Grant - others:EU(XE) FP7-PEOPLE-ITN No.238511 Institutional support: RVO:60077344 Keywords : Ehrlichia * Rhipicephalus (Boophilus) microplus * in vitro culture * tick cell * DH82 * endothelial cell * cattle * 16S rRNA * Brazil Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 3.116, year: 2013

  2. Influence of UV-radiation on granulocytic phagocytosis in vitro

    International Nuclear Information System (INIS)

    Walther, T.; Rytter, M.; Gast, W.; Haustein, U.F.

    1987-01-01

    The influence of UV radiation on the vitality, the performance of phagocytosis and the ability to reduce nitro-blue tetrazolium test (NBT) by human granulocytes was investigated in vitro. Already by low doses of UVA (8% UVB) the percentage of phagocytizing granulocytes was decreased more distinctly than their cell vitality. The number of ingested Candida albicans particles was 4.5 particles per granulocyte in the controls. It was reduced to about 1.4 particles per cell by UV radiation independent of the dosis applied. On the other hand the ability of granulocytes to reduce NBT intracellularly remained completely unchanged. (author)

  3. Seroprevalencia de Leptospira sp., Rickettsia sp. Ehrlichia sp. en trabajadores rurales del departamento de Sucre, Colombia Seroprevalence of Leptospira sp., Rickettsia sp. and Ehrlichia sp. in rural workers of Sucre, Colombia

    Directory of Open Access Journals (Sweden)

    Rodrigo Ríos

    2008-06-01

    Full Text Available Objective. Determinar la seroprevalencia de Leptospira sp., Rickettsia sp. y Ehrlichia sp. en trabajadores de áreas rurales del departamento de Sucre. Material y métodos. Se realizó un estudio escriptivo, prospectivo, de corte transversal, que pretendió determinar la seroprevalencia e Leptospira sp., Rickettsia sp. y Ehrlichia sp. en 90 trabajadores de áreas rurales del departamento de Sucre. Se estableció la presencia de anticuerpos séricos anti-IgM específicos anti-Leptospira por la técnica de ELISA indirecta. Para la determinación de Rickettsia sp. y Ehrlichia sp. se uso la técnica de inmunofluorescencia indirecta. Resultados. La población evaluada estaba compuesta por 27 (30% ordeñadores, 21 (23% jornaleros, 18 (20% profesionales del campo y 24 (27% que realizaban otras actividades. Ventidós (24% muestras resultaron positivas en alguna de las pruebas. De éstas, 12 (13,3% fueron positivas para Leptospira sp., 7 (7,8% para Rickettsia sp. y 3 (3,3% ara Ehrlichia sp. Conclusión. Este fue el primer estudio que se llevó a cabo en el departamento de Sucre y permitió demostrar que existe una prevalencia importante de Leptospira p.,Rickettsia sp. y Ehrlichia sp.. Los factores de riesgo ocupacional fueron factores determinantes en la seropositividad.Objective. To determine the seroprevalence of Leptospira sp., Rickettsia sp. and Ehrlichia sp. in agricultural workers of Sucre. Methods. A descriptive prospective cross-sectional study was conducted in ninety rural workers of Sucre. Presence of serum antibodies anti-IgM specific anti-Leptospira by indirect ELISA was established. For the determination of Rickettsia and Ehrlichia indirect inmunoflorescence was used. Results.The population was composed by 27 (30% milkers, 21 (23% day workers, 18 farm professionals (20% and 24 (26% workers in others activities. A total of 22 (24% samples were positive to some test. Twelve (13.3% were positive to Leptospira sp., seven (7.8% to Rickettsia sp

  4. Granulocytic sarcoma: a rare cause of sciatica.

    Science.gov (United States)

    Valsamis, Epaminondas Markos; Glover, Thomas Edward

    2017-02-15

    We describe a case report of a man aged 56 years with a 4-month history of right-sided sciatica-type pain with subclinical disc prolapse evident on MRI. Worsening pain together with the appearance of a tender mass in his right buttock prompted further imaging, which demonstrated an infiltrative mass engulfing the lumbosacral plexus. This was later shown to be a granulocytic sarcoma on biopsy. Intervertebral disc herniation can be an incidental finding and is not always the cause of sciatica. 2017 BMJ Publishing Group Ltd.

  5. Haematopathological Changes in Dogs Affected with Ehrlichia Canis in Lesvos

    Directory of Open Access Journals (Sweden)

    Geromichalou A.

    2017-06-01

    Full Text Available Canine Ehrlichiosis is an important immunosuppressive tick borne disease in dogs. The geographical distribution and transmission is mostly related with Rhipicephalus sanguineus which acts as a vector. There is no predilection of age or sex; all breeds may be infected with Canine Monocytic Ehrlichiosis (CME. The primary targets are monocytic cells. Platelet disorders and serum protein alterations are the principal hematological and biochemical consequences of infections. Clinical signs are almost non-specific. A definitive diagnosis requires: visualization of morulae within monocytes on cytology, detection of serum antibodies with E. canis, the IFA test, or the PCR. The objective of this study was to present information about haematological and biochemical tests of E. canis infected dogs in Lesvos island in Greece, which is an endemic area.

  6. The redistribution of granulocytes following E. coli endotoxin induced sepsis

    DEFF Research Database (Denmark)

    Toft, P; Lillevang, S T; Tønnesen, Else Kirstine

    1994-01-01

    Infusion of endotoxin elicits granulocytopenia followed by increased numbers of granulocytes in peripheral blood. The purpose of this study was to investigate the redistribution and sequestration of granulocytes in the tissues following E. coli endotoxin induced sepsis. From 16 rabbits granulocytes...... were isolated, labelled with Indium and reinjected intravenously. Eight rabbits received an infusion of E. coli endotoxin 2 micrograms kg-1 while eight received isotonic saline. The redistribution of granulocytes was imaged with a gamma camera and calculated with a connected computer before and 2 and 6...... hours after infusion of endotoxin or saline. Serum cortisol and interleukin-1 beta were measured. In another seven rabbits, respiratory burst activity and degranulation of granulocytes were measured prior to and from 5 min to 6 hours after infusion of E. coli endotoxin 2 micrograms kg-1 BW. Following...

  7. Possible death of a buffalo calf (Syncercus caffer due to suspected heartwater (Ehrlichia ruminantium : clinical communication

    Directory of Open Access Journals (Sweden)

    S. Pfitzer

    2004-06-01

    Full Text Available Rickettsial organisms resembling Ehrlichia ruminantium (the causative organism of heartwater were demonstrated in brain smears and formalin-fixed brain sections derived from a buffalo calf that died on a private game reserve in northern KwaZulu-Natal. The possibility that the tick-free environment of a quarantine boma may have affected the calf 's immunity, is discussed. These findings suggest that monitoring heartwater in wild ruminants and making brain smears as a routine during post mortem evaluations of wild ruminants, should be encouraged.

  8. Ehrlichia canis morulae and DNA detection in whole blood and spleen aspiration samples.

    Science.gov (United States)

    Faria, Joice Lara Maia; Dagnone, Ana Sílvia; Munhoz, Thiago Demarchi; João, Carolina Franchi; Pereira, Wanderson Adriano Biscola; Machado, Rosângela Zacarias; Tinucci-Costa, Mirela

    2010-01-01

    The aim of this study was to compare the detection of Ehrlichia canis morulae and DNA by nPCR in whole blood and spleen aspiration. The sample included 40 dogs showing thrombocytopenia associated to clinical signs suggestive of canine ehrlichiosis. Morulae detection showed that in 35 of the dogs studied, 17 had morulae in spleen tissue, and two in buffy coat smears. E. canis DNA was detected in 29/40 blood samples. We verified that morulae detection is more efficient in cytological preparations from spleen aspiration. On the other hand, nPCR on spleen and blood samples were equally efficient for disease diagnosis.

  9. Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

    Directory of Open Access Journals (Sweden)

    Taslima T. Lina

    2016-07-01

    Full Text Available Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E. chaffeensis type 1 secreted tandem repeat protein (TRP effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E. chaffeensis, via the TRP120 effector, activates the canonical Notch signaling pathway to promote intracellular survival. We found that nuclear translocation of the transcriptionally active Notch intracellular domain (NICD occurs in response to E. chaffeensis or recombinant TRP120, resulting in upregulation of Notch signaling pathway components and target genes notch1, adam17, hes, and hey. Significant differences in canonical Notch signaling gene expression levels (>40% were observed during early and late stages of infection, indicating activation of the Notch pathway. We linked Notch pathway activation specifically to the TRP120 effector, which directly interacts with the Notch metalloprotease ADAM17. Using pharmacological inhibitors and small interfering RNAs (siRNAs against γ-secretase enzyme, Notch transcription factor complex, Notch1, and ADAM17, we demonstrated that Notch signaling is required for ehrlichial survival. We studied the downstream effects and found that E. chaffeensis TRP120-mediated activation of the Notch pathway causes inhibition of the extracellular signal-regulated kinase 1/2 (ERK1/2 and p38 mitogen-activated protein kinase (MAPK pathways required for PU.1 and subsequent Toll-like receptor 2/4 (TLR2/4 expression. This investigation reveals a novel mechanism whereby E. chaffeensis exploits the Notch pathway to evade the host innate immune response for intracellular survival.

  10. Granulocyte-platelet interactions and platelet fibrinogen receptor exposure

    International Nuclear Information System (INIS)

    Kornecki, E.; Ehrlich, Y.H.; Egbring, R.; Gramse, M.; Seitz, R.; Eckardt, A.; Lukasiewicz, H.; Niewiarowski, S.

    1988-01-01

    The authors have examined the interaction of human granulocyte elastase with human platelets. Incubation of human platelets with human granulocyte elastase exposed active fibrinogen-binding sites as evidenced by 125 I-labeled fibrinogen binding and spontaneous fibrinogen-induced platelet aggregation. The aggregation of platelets by fibrinogen occurred at low concentrations of human granulocyte elastase. Platelets pretreated with human granulocyte elastase exposed an average of 10,500 fibrinogen-binding sites per platelet, i.e., about one-third the number of binding sites exposed by optimal concentrations of ADP. With the use of a polyclonal antiplatelet membrane antibody, the glycoproteins IIb (GPIIb), IIIa (GPIIIa), and a 60,000-Da (60 kDa) protein (66 kDa in a reduced system) derived from GPIIIa were immunoprecipitated from the surface of detergent extracts of human 125 I-radiolabeled platelets pretreated with increasing concentrations of human granulocyte elastase. They conclude that (1) the proteolytic action of human granulocyte elastase on platelet GPIIIa results in the formation of two major hydrolytic products, and (2) human granulocyte elastase exposes active fibrongen-binding sites associated with the GPIIb/GPIIIa complex, resulting in direct platelet aggregation by fibrinogen

  11. Conservation of myeloid surface antigens on primate granulocytes.

    Science.gov (United States)

    Letvin, N L; Todd, R F; Palley, L S; Schlossman, S F; Griffin, J D

    1983-02-01

    Monoclonal antibodies reactive with myeloid cell surface antigens were used to study evolutionary changes in granulocyte surface antigens from primate species. Certain of these granulocyte membrane antigens are conserved in phylogenetically distant species, indicating the potential functional importance of these structures. The degree of conservation of these antigens reflects the phylogenetic relationship between primate species. Furthermore, species of the same genus show similar patterns of binding to this panel of anti-human myeloid antibodies. This finding of conserved granulocyte surface antigens suggests that non-human primates may provide a model system for exploring uses of monoclonal antibodies in the treatment of human myeloid disorders.

  12. The role of granulocyte macrophage-colony stimulating factor in gastrointestinal immunity to salmonellosis.

    Science.gov (United States)

    Coon, C; Beagley, K W; Bao, S

    2009-08-01

    Human Salmonella infection, in particular, typhoid fever is a highly infectious disease that remains a major public health problem causing significant morbidity and mortality. The outcome of these infections depends on the host's immune response, particularly the actions of granulocytes and macrophages. Using a mouse model of human typhoid fever, with Salmonella typhimurium infection of wild type and granulocyte macrophage-colony stimulating factor (GM-CSF) knock out mice we show a delay in the onset of immune-mediated tissue damage in the spleens and livers of GM-CSF(-/-) mice. Furthermore, GM-CSF(-/-) mice have a prolonged sequestration of S. typhimurium in affected tissues despite an increased production of F4/80+ effector cells. Moreover in the absence of GM-CSF, a decrease in pro-inflammatory cytokine expression of tumor necrosis factor-alpha, interleukin-12 (IL-12) and IL-18 was found, which may alter the host's immune response to infection. GM-CSF appears to play an important role in the pathogenesis of Salmonellosis, and may contribute significantly to the development of protective gastrointestinal mucosal immune responses against oral pathogens.

  13. Ehrlichia Meningitis Mimicking Aneurysmal Subarachnoid Hemorrhage: A Case Study for Medical Decision-Making Heuristics.

    Science.gov (United States)

    Dredla, Brynn; Freeman, William D

    2016-04-01

    Thunderclap headache is a sudden and severe headache that can occur after an aneurysmal subarachnoid hemorrhage (SAH). Subarachnoid hemorrhage is a medical emergency that requires prompt attention and hospitalization. Patients with thunderclap headache often undergo a noncontrast head computed tomography (CT) scan to ascertain SAH bleeding and, if the scan is negative, then undergo a lumbar puncture to look for cerebrospinal fluid (CSF) red blood cells (RBCs), which would be consistent with an aneurysmal leak. If the initial CT is negative and CSF is positive for RBCs, patients are usually admitted to the hospital for evaluation of intracranial aneurysm. We encountered a patient with thunderclap headache whose initial head CT was negative for SAH and whose CSF tested positive for RBCs. The patient was referred to our center for evaluation and management of aneurysmal SAH. However, on careful review of the patient's medical history, serum laboratory values, and spinal fluid values, the patient was diagnosed with Ehrlichia chaffeensis meningitis. While Ehrlichia meningitis is rare, it is important to recognize the clinical clues that could help avoid formal cerebral angiography, a costly and potentially unnecessary procedure. We present how this case represented a cognitive framing bias and anchoring heuristic as well as steps that medical providers can use to prevent such cognitive errors in diagnosis.

  14. Novel genotype of Ehrlichia canis detected in samples of human blood bank donors in Costa Rica.

    Science.gov (United States)

    Bouza-Mora, Laura; Dolz, Gaby; Solórzano-Morales, Antony; Romero-Zuñiga, Juan José; Salazar-Sánchez, Lizbeth; Labruna, Marcelo B; Aguiar, Daniel M

    2017-01-01

    This study focuses on the detection and identification of DNA and antibodies to Ehrlichia spp. in samples of blood bank donors in Costa Rica using molecular and serological techniques. Presence of Ehrlichia canis was determined in 10 (3.6%) out of 280 blood samples using polymerase chain reaction (PCR) targeting the ehrlichial dsb conserved gene. Analysis of the ehrlichial trp36 polymorphic gene in these 10 samples revealed substantial polymorphism among the E. canis genotypes, including divergent tandem repeat sequences. Nucleotide sequences of dsb and trp36 amplicons revealed a novel genotype of E. canis in blood bank donors from Costa Rica. Indirect immunofluorescence assay (IFA) detected antibodies in 35 (35%) of 100 serum samples evaluated. Thirty samples showed low endpoint titers (64-256) to E. canis, whereas five sera yielded high endpoint titers (1024-8192); these five samples were also E. canis-PCR positive. These findings represent the first report of the presence of E. canis in humans in Central America. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. In vitro culture and structural differences in the major immunoreactive protein gp36 of geographically distant Ehrlichia canis isolates

    Czech Academy of Sciences Publication Activity Database

    Zweygarth, E.; Cabezas Cruz, Alejandro; Josemans, A.I.; Oosthuizen, M.C.; Matjila, P.T.; Lis, K.; Broniszewska, M.; Schöl, H.; Ferrolho, J.; Grubhoffer, Libor; Passos, L.M.F.

    2014-01-01

    Roč. 5, č. 4 (2014), s. 423-431 ISSN 1877-959X Institutional support: RVO:60077344 Keywords : Ehrlichia canis * In vitro culture * IDE8 tick cells * DH82 * 16S rRNA * gp36 Subject RIV: FN - Epidemiology, Contagious Diseases ; Clinical Immunology Impact factor: 2.718, year: 2014

  16. Granulocytic Sarcoma of the Stomach Presenting as Dysphagia during Pregnancy

    Directory of Open Access Journals (Sweden)

    Anuradha Sekaran

    2011-01-01

    Full Text Available Granulocytic sarcoma also known as extramedullary myeloid sarcoma or chloroma is an uncommon manifestation of leukemia and presents as a deposit of leukemic cells outside the bone marrow. We report a case of a twenty-five-year-old pregnant woman who presented with progressive dysphagia and recurrent postprandial vomiting. Upper GI endoscopy had shown large flat laterally spread nodular lesions in the cardia and proximal body of stomach. Biopsies from the gastric lesion showed granulocytic sarcoma of the stomach. Concurrent peripheral and bone marrow picture was suggestive of acute myeloid leukemia (AML–M4. There is limited reported literature on granulocytic sarcoma of the stomach. Concurrent gastric granulocytic sarcoma involving cardia and AML in pregnancy has not been reported till date.

  17. Hungry granulocyte: its fate and regulation of production

    International Nuclear Information System (INIS)

    Cronkite, E.P.

    1978-01-01

    The granulocyte, a phagocytic anti-1 bacterial defense cell, is discussed. Its production, the kinetics of its proliferation, the regulation of its production, and its loss from the blood are reviewed

  18. Indium-111 granulocyte scintigraphy in inflammatory bowel disease

    International Nuclear Information System (INIS)

    Devillers, A.; Moisan, A.; Heresbach, D.; Darnault, P.; Bretagne, J.F.

    1996-01-01

    The present paper reports our experience since 1963 concerning 111-indium labeled autologous granulocytes scanning in the assessment of inflammatory bowel diseases and in the assessment of activity in Crohn's disease and ulcerative colitis. (authors). 94 refs., 3 figs

  19. Soroprevalência e fatores de risco associados à soropositividade para Ehrlichia canis em cães do semiárido da Paraíba

    Directory of Open Access Journals (Sweden)

    Sérgio Santos de Azevedo

    2011-02-01

    Full Text Available Aiming to determine the seroprevalence of Ehrlichia canis infection, as well as to identify risk factors associated to the seropositivity, a serological survey was conducted in 109 dogs assisted at the Hospital Veterinário/Centro de Saúde e Tecnologia Rural (CSTR/Universidade Federal de Campina Grande (UFCG, Campus de Patos, Paraíba State, Northeastern Brazil. Serological diagnosis of ehrlichiosis was performed by the indirect fluorescent antibody test (IFAT and sera presenting antibody titers >; 40 were considered positive. Of the 109 samples, 72.5% were positive (95% CI = 63.1% - 80.6%. Animals that had contact with other dogs (odds ratio = 3.59; 95% CI = 1.41 - 9.12, contact with ponds (odds ratio = 8.39; 95% CI = 1.01 - 69.87 or with free access to the street (odds ratio = 6.24; 95% CI = 1.28 - 30.39 were more exposed to the risk of infection.

  20. A serological and molecular survey of Babesia vogeli, Ehrlichia canis and Rickettsia spp. among dogs in the state of Maranhão, northeastern Brazil

    Directory of Open Access Journals (Sweden)

    Andréa Pereira da Costa

    Full Text Available This study evaluated exposure and infection by tick-borne agents (Babesia vogeli, Ehrlichia canis and Rickettsia spp. in 172 dogs in rural areas and 150 dogs in urban areas of the municipality of Chapadinha, state of Maranhão, northeastern Brazil, using molecular and serological methods. Overall, 16.1% of the sampled dogs (52/322 were seroreactive to B. vogeli, with endpoint titers ranging from 40 to 640. For E. canis, 14.6% of the dogs (47/322 were seroreactive, with endpoint titers from 80 to 163,840. Antibodies reactive to at least one of the five species of Rickettsia were detected in 18.9% of the dogs (61/322, with endpoint titers ranging from 64 to 4,096. High endpoint titers were observed for Rickettsia amblyommii. Three (0.9% and nine (2.8% canine blood samples were PCR-positive for Babesia spp. and E. canis. The ticks collected from urban dogs were all Rhipicephalus sanguineus sensu lato, whereas the rural dogs were infested by R. sanguineus s.l, Amblyomma cajennense sensu lato and Amblyomma ovale. One A. ovale tick was found to be infected by Rickettsia bellii. This study provides an epidemiological background for controlling and preventing canine tick-borne diseases in a neglected region of Brazil.

  1. Molecular detection of Anaplasma platys, Anaplasma phagocytophilum and Wolbachia sp. but not Ehrlichia canis in Croatian dogs.

    Science.gov (United States)

    Huber, Doroteja; Reil, Irena; Duvnjak, Sanja; Jurković, Daria; Lukačević, Damir; Pilat, Miroslav; Beck, Ana; Mihaljević, Željko; Vojta, Lea; Polkinghorne, Adam; Beck, Relja

    2017-11-01

    The bacteria Anaplasma platys, Anaplasma phagocytophilum and Ehrlichia canis are tick-borne agents that cause canine vector-borne disease. The prevalence of these pathogens in South Eastern Europe is unknown with the exception of an isolated case of A. platys detected in a dog imported into Germany from Croatia. To gain a better insight into their presence and prevalence, PCR-based screening for these bacterial pathogens was performed on domesticated dogs from different regions of Croatia. Blood samples from 1080 apparently healthy dogs from coastal and continental parts of Croatia as well as tissue samples collected from 63 deceased dogs with a history of anaemia and thrombocytopenia were collected for molecular screening by an Anaplasmataceae-specific 16S rRNA conventional PCR. Positive samples were confirmed using a second Anaplasmataceae-specific PCR assay with the PCR product sequenced for the purpose of bacterial species identification. All sequenced isolates were georeferenced and a kernel intensity estimator was used to identify clusters of greater case intensity. 42/1080 (3.8%; CI 2.7-5.0) of the healthy dogs were PCR positive for bacteria in the Anaplasmataceae. Sequencing of the 16S rRNA gene amplified from these positive samples revealed the presence of A. platys in 2.5% (CI 1.6-3.4%, 27 dogs), A. phagocytophilum in 0.3% (CI 0-0.6%, 3 dogs) and a Wolbachia endosymbiont in 1.1% (CI 0.4-1.6%, 12 dogs) of dogs screened in this study. Necropsied dogs were free from infection. Notably, no evidence of E. canis infection was found in any animal. This survey represents a rare molecular study of Anaplasmataceae in dogs in South Eastern Europe, confirming the presence of A. platys and A. phagocytophilum but not E. canis. The absence of E. canis was surprising given it has been described in all other Mediterranean countries surveyed and raises questions over the regional vector capacity of the Rhipicephalus sanguineus tick.

  2. Comparison of Ehrlichia muris Strains Isolated from Wild Mice and Ticks and Serologic Survey of Humans and Animals with E. muris as Antigen

    OpenAIRE

    Kawahara, Makoto; Ito, Tadahiko; Suto, Chiharu; Shibata, Shinichiro; Rikihisa, Yasuko; Hata, Kazuhisa; Hirai, Katsuya

    1999-01-01

    In metropolitan Tokyo, the Ehrlichia muris seropositivity rate of 24 wild mice was 63% in Hinohara Village, but in the surrounding areas, it was 0 to 5%. This finding suggests that the reservoir of E. muris is focal. Among the 15 seropositive mice, ehrlichiae were isolated from 9 Apodemus speciosus mice and 1 A. argenteus mouse, respectively. Five ehrlichial isolates were obtained from 10 ticks (Haemaphysalis flava) collected in Asuke Town, Aichi Prefecture, where the E. muris type strain had...

  3. Granulocyte colony-stimulating factor in glycogen storage disease type 1b. Results of the European Study on Glycogen Storage Disease Type 1

    NARCIS (Netherlands)

    Visser, G.; Rake, J.P.; Labrune, P.; Leonard, J.V.; Moses, S.; Ullrich, K.; Wendel, U.; Groenier, K.H.; Smit, G.P.

    2002-01-01

    Patients with glycogen storage disease type 1b (GSD-1b) have neutropenia and neutrophil dysfunction that predispose to frequent infections and inflammatory bowel disease (IBD), for which granulocyte colony-stimulating factor (GCSF) is given. To investigate the use and the value of GCSF treatment in

  4. Regulation of granulocyte colony-stimulating factor receptor-mediated granulocytic differentiation by C-mannosylation.

    Science.gov (United States)

    Otani, Kei; Niwa, Yuki; Suzuki, Takehiro; Sato, Natsumi; Sasazawa, Yukiko; Dohmae, Naoshi; Simizu, Siro

    2018-04-06

    Granulocyte colony-stimulating factor (G-CSF) receptor (G-CSFR) is a type I cytokine receptor which is involved in hematopoietic cell maturation. G-CSFR has three putative C-mannosylation sites at W253, W318, and W446; however, it is not elucidated whether G-CSFR is C-mannosylated or not. In this study, we first demonstrated that G-CSFR was C-mannosylated at only W318. We also revealed that C-mannosylation of G-CSFR affects G-CSF-dependent downstream signaling through changing ligand binding capability but not cell surface localization. Moreover, C-mannosylation of G-CSFR was functional and regulated granulocytic differentiation in myeloid 32D cells. In conclusion, we found that G-CSFR is C-mannosylated at W318 and that this C-mannosylation has role(s) for myeloid cell differentiation through regulating downstream signaling. Copyright © 2018 Elsevier Inc. All rights reserved.

  5. Factores asociados a la infección por Ehrlichia canis en perros infestados con garrapatas en la ciudad de Huánuco, Perú

    Directory of Open Access Journals (Sweden)

    Edward Huerto-Medina

    Full Text Available El objetivo del estudio fue determinar la frecuencia y factores asociados a la infección por Ehrlichia canis en perros. Se recolectaron muestras de sangre de 150 perros infestados con garrapatas en 10 consultorios veterinarios de la ciudad de Huánuco en Perú, los perros fueron seleccionados al azar sin distinción de raza, edad ni sexo. Se detectó anticuerpos contra Ehrlichia canis mediante inmunoensayo cromatográfico. El 51,3% de perros estuvieron infectados por Ehrlichia canis. En el análisis multivariado se encontraron asociados a la presencia Ehrlichia canis, el mal estado de salud del perro (p=0,049, un promedio mayor de infestación por garrapatas (p=0,018, perros de edad adulta (p=0,038. La frecuencia de Ehrlichia canis en perros de esta ciudad es alta. Se recomienda el control de la garrapata marrón del perro (Rhipicephalus sanguineus vector de la Ehrlichia canis

  6. Granulocyte colony-stimulating factor and leukemogenesis

    Directory of Open Access Journals (Sweden)

    Lorena Lobo de Figueiredo

    2004-01-01

    Full Text Available THE granulocyte colony-stimulating factor (G-CSF plays an important role in normal granulopoiesis. Its functions are mediated by specific receptors on the surface of responsive cells and, upon ligand binding, several cytoplasmic tyrosine kinases are activated. The cytoplasmic region proximal to the membrane of the G-CSF receptor (G-CSF-R transduces proliferative and survival signals, whereas the distal carboxy-terminal region transduces maturation signals and suppresses the receptor's proliferative signals. Mutations in the G-CSF-R gene resulting in truncation of the carboxy-terminal region have been detected in a subset of patients with severe congenital neutropenia who developed acute myelogenous leukemia (AML. In addition, the AML1-ETO fusion protein, expressed in leukemic cells harboring the t(8;21, disrupt the physiological function of transcription factors such as C/EBPα and C/EBPε, which in turn deregulate G-CSF-R expression. The resulting high levels of G-CSF-R and G-CSF-dependent cell proliferation may be associated with pathogenesis of AML with t(8;21. Moreover, in vitro and in vivo studies demonstrated that G-CSF may act as a co-stimulus augmenting the response of PML-RARα acute promyelocytic leukemia cells to all-trans-retinoic acid treatment. Finally, in the PLZF-RARα acute promyelocytic leukemia transgenic model, G-CSF deficiency suppressed leukemia development. Altogether, these data suggest that the G-CSF signaling pathway may play a role in leukemogenesis.

  7. Radiation Therapy for Chloroma (Granulocytic Sarcoma)

    Energy Technology Data Exchange (ETDEWEB)

    Bakst, Richard; Wolden, Suzanne [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States); Yahalom, Joachim, E-mail: yahalomj@mskcc.org [Department of Radiation Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY (United States)

    2012-04-01

    Objectives: Chloroma (granulocytic sarcoma) is a rare, extramedullary tumor of immature myeloid cells related to acute nonlymphocytic leukemia or myelodysplastic syndrome. Radiation therapy (RT) is often used in the treatment of chloromas; however, modern studies of RT are lacking. We reviewed our experience to analyze treatment response, disease control, and toxicity associated with RT to develop treatment algorithm recommendations for patients with chloroma. Patients and Methods: Thirty-eight patients who underwent treatment for chloromas at our institution between February 1990 and June 2010 were identified and their medical records were reviewed and analyzed. Results: The majority of patients that presented with chloroma at the time of initial leukemia diagnosis (78%) have not received RT because it regressed after initial chemotherapy. Yet most patients that relapsed or remained with chloroma after chemotherapy are in the RT cohort (90%). Thirty-three courses of RT were administered to 22 patients. Radiation subsite breakdown was: 39% head and neck, 24% extremity, 9% spine, 9% brain, 6% genitourinary, 6% breast, 3% pelvis, and 3% genitourinary. Median dose was 20 (6-36) Gy. Kaplan-Meier estimates of progression-free survival and overall survival in the RT cohort were 39% and 43%, respectively, at 5 years. At a median follow-up of 11 months since RT, only 1 patient developed progressive disease at the irradiated site and 4 patients developed chloromas at other sites. RT was well tolerated without significant acute or late effects and provided symptom relief in 95% of cases. Conclusions: The majority of patients with chloromas were referred for RT when there was extramedullary progression, marrow relapse, or rapid symptom relief required. RT resulted in excellent local disease control and palliation of symptoms without significant toxicity. We recommend irradiating chloromas to at least 20 Gy, and propose 24 Gy in 12 fractions as an appropriate regimen.

  8. Granulocytes: New Members of the Antigen-Presenting Cell Family

    Directory of Open Access Journals (Sweden)

    Ang Lin

    2017-12-01

    Full Text Available Granulocytes, the most abundant types of leukocytes, are the first line of defense against pathogen invasion. However, the plasticity and diversity of granulocytes have been increasingly revealed, especially with regard to their versatile functions in orchestrating adaptive immune responses. A substantial body of recent evidence demonstrates that granulocytes can acquire the function as antigen-presenting cells under pathological or inflammatory conditions. In addition, they can acquire surface expression of MHC class II and costimulatory molecules as well as T cell stimulatory behavior when cultured with selected cytokines. The classic view of granulocytes as terminally differentiated, short-lived phagocytes is therefore changing to phenotypically and functionally heterogeneous cells that are engaged in cross-talk with other leukocyte populations and provide an additional link between innate and adaptive immunity. In this brief review, we summarize the current knowledge on the antigen-presenting capacity of granulocyte subsets (neutrophils, eosinophils, and basophils. Underlying mechanisms, relevant physiological significance and potential controversies are also discussed.

  9. Ehrlichia chaffeensis TRP120 Activates Canonical Notch Signaling To Downregulate TLR2/4 Expression and Promote Intracellular Survival

    OpenAIRE

    Lina, Taslima T.; Dunphy, Paige S.; Luo, Tian; McBride, Jere W.

    2016-01-01

    ABSTRACT Ehrlichia chaffeensis preferentially targets mononuclear phagocytes and survives through a strategy of subverting innate immune defenses, but the mechanisms are unknown. We have shown E.?chaffeensis type 1 secreted tandem repeat protein (TRP) effectors are involved in diverse molecular pathogen-host interactions, such as the TRP120 interaction with the Notch receptor-cleaving metalloprotease ADAM17. In the present study, we demonstrate E.?chaffeensis, via the TRP120 effector, activat...

  10. Granulocytic sarcoma of the ovary in a nonleukemic patient.

    Science.gov (United States)

    Aguiar, R C; Pozzi, D H; Chamone, D A

    1993-01-01

    We report a case of granulocytic sarcoma of the ovary preceding acute myeloid leukemia by twelve months, with no evidence of any hematological involvement at the time of first diagnosis. The patient was initially treated with surgery and chemotherapy for undifferentiated lymphoma and, although this aggressive protocol resulted in a complete response, granulocytic sarcoma recurred as extramedullary disease, followed by the appearance of acute myeloid leukemia. We discuss the clinical, histopathological and immunohistochemical features of the disease, the differential diagnosis and, in particular, the role of early aggressive treatment on the outcome of the patient.

  11. Detection of Ehrlichia spp., Anaplasma spp., Rickettsia spp., and other eubacteria in ticks from the Thai-Myanmar border and Vietnam.

    Science.gov (United States)

    Parola, Philippe; Cornet, Jean-Paul; Sanogo, Yibayiri Osée; Miller, R Scott; Thien, Huynh Van; Gonzalez, Jean-Paul; Raoult, Didier; Telford III, Sam R; Wongsrichanalai, Chansuda

    2003-04-01

    A total of 650 ticks, including 13 species from five genera, were collected from animals, from people, or by flagging of the vegetation at sites on the Thai-Myanmar border and in Vietnam. They were tested by PCR to detect DNA of bacteria of the order RICKETTSIALES: Three Anaplasma spp. were detected in ticks collected in Thailand, including (i) Anaplasma sp. strain AnDa465, which was considered a genotype of Anaplasma platys (formerly Ehrlichia platys) and which was obtained from Dermacentor auratus ticks collected from dogs; (ii) Anaplasma sp. strain AnAj360, which was obtained from Amblyomma javanense ticks collected on a pangolin; and (iii) Anaplasma sp. strain AnHl446, which was closely related to Anaplasma bovis and which was detected in Haemaphysalis lagrangei ticks collected from a bear. Three Ehrlichia spp. were identified, including (i) Ehrlichia sp. strain EBm52, which was obtained from Boophilus microplus ticks collected from cattle from Thailand; (ii) Ehrlichia sp. strain EHh324, which was closely related to Ehrlichia chaffeensis and which was detected in Haemaphysalis hystricis ticks collected from wild pigs in Vietnam; and (iii) Ehrlichia sp. strain EHh317, which was closely related to Ehrlichia sp. strain EBm52 and which was also detected in H. hystricis ticks collected from wild pigs in Vietnam. Two Rickettsia spp. were detected in Thailand, including (i) Rickettsia sp. strain RDla420, which was detected in Dermacentor auratus ticks collected from a bear, and (ii) Rickettsia sp. strain RDla440, which was identified from two pools of Dermacentor larvae collected from a wild pig nest. Finally, two bacteria named Eubacterium sp. strain Hw124 and Eubacterium sp. strain Hw191 were identified in Haemaphysalis wellingtoni ticks collected from chicken in Thailand; these strains could belong to a new group of bacteria.

  12. Kinetic data of in-vivo labeled granulocytes in humans with a murine Tc-99m-labelled monoclonal antibody

    International Nuclear Information System (INIS)

    Becker, W.; Boerner, W.; Borst, U.; Schaefer, R.; Fischbach, W.; Pasurka, B.

    1989-01-01

    Twenty-five patients were examined in vivo with 99m Tc labelled monoclonal antibodies; 15 with suspected infections with an antigranulocyte antibody (BW 250/183), 10 with suspected recurrence of a colorectal carcinoma with an anti CEA antibody (BW 431/26). Both antibodies were IgG1 isotypes. In the patients with suspected infections no change of the peripheral leukocyte count could be observed after the antibody injection (1 mg, n=9; 0.05 mg, n=1; 0.25 mg, n=6). In 2 patients examined with the anti CEA antibody (2 mg), a significant decrease of the peripheral leukocyte count could be observed. The recovery rate of the 99m Tc antibody labelled granulocytes was calculated to be about 10%. The increase of the antibody-antigen binding was calculated to be 0.2%/min. In vivo the organ distribution curves demonstrated an increase of 99m Tc activity over spleen and bone marrow of 1.1%/min, which was interpreted as antigen-antibody reactivity. The organ distribution curves of the anti granulocyte antibody over spleen and bone marrow showed typical binding characteristics to the local granulocyte epitopes. The curves over other organs showed a simple perfusion pattern. The curves of the anti CEA antibody showed a perfusion pattern over all the examined organs. A sham dialysis model in one patient with renal insufficiency undergoing regular dialysis treatment demonstrated the viability of 99m Tc antibody labelled granulocytes in vivo. The kinetic patterns of the 99m Tc antibody in patients with Crohn's disease were interpreted as CEA binding of the antibody in the bowel wall. (orig.)

  13. Undifferentiated granulocytic sarcoma: a case with epidural onset preceding acute promyelocytic leukemia.

    Science.gov (United States)

    Tosi, A; De Paoli, A; Fava, S; Luoni, M; Sironi, M; Tocci, A; Assi, A; Cassi, E

    1995-01-01

    This study reports a case of granulocytic sarcoma that developed in the epidural zone 25 days before clinical evidence of an acute promyelocytic leukemia. The case presented the diagnostic difficulties that are common to all aleukemic granulocytic sarcomas. Moreover, it highlights the very rare association between granulocytic sarcoma and acute promyelocytic leukemia, which is far from being explained.

  14. Hepatozoon ellisgreineri n. sp. (Hepatozoidae): description of the first avian apicomplexan blood parasite inhabiting granulocytes.

    Science.gov (United States)

    Valkiūnas, Gediminas; Mobley, Kristin; Iezhova, Tatjana A

    2016-02-01

    Blood parasites of the genus Hepatozoon (Apicomplexa, Hepatozoidae) infect all groups of terrestrial vertebrates, and particularly high prevalence and species diversity have been reported in reptiles and mammals. A few morphologically similar species, in which gamonts inhabit mononuclear leukocytes and red blood cells, have been described in birds. Here, we report a new Hepatozoon species, which was found in wild-caught secretary birds Sagittarius serpentarius, from Tanzania. Hepatozoon ellisgreineri n. sp. can be readily distinguished from all described species of avian Hepatozoon because its gamonts develop only in granulocytes, predominantly in heterophils, a unique characteristic among bird parasites of this genus. Additionally, this is the first reported avian apicomplexan blood parasite, which inhabits and matures in granulocytes. We describe H. ellisgreineri based on morphological characteristics of blood stages and their host cells. This finding broadens knowledge about host cells of avian Hepatozoon spp. and other avian apicomplexan blood parasites, contributing to the better understanding of the diversity of haematozoa. This is the first report of hepatozoonosis in endangered African birds of the Sagittariidae.

  15. Imaging diagnosis of Granulocytic Sarcoma in the skull base

    International Nuclear Information System (INIS)

    Zheng Shaoyan; Xie Jiming; Yang Zhiyun; Zhou Zhou; Li Shurong

    2010-01-01

    Objective: To improve the understanding and imaging diagnosis of granulocytic sarcoma in the skull base. Methods: Three cases of granulocytic sarcomas in the skull base are reported. The clinical features and imaging findings were analyzed. Results: The three cases occurred in children with acute myeloid leukemia. Two patients presented with oculomotor paralysis before the diagnosis of leukemia, the third patient with history of leukemia presented with headache. Diffuse infiltration of basal skull bone marrow and extracranial soft tissue masses were shown on MRI. The signal intensities of the masses were similar to that of gray matter on T 1 WI and T 2 WI with marked contrast enhancement. The soft tissue masses were located in the para-sellar region and surrounded the lateral wall of the maxillary sinus in one case. The soft tissue mass of the second case infiltrated the orbital cavity, cavernous sinus and oculomotor nerve. Tumor infiltrating the meninges, cranial nerves and paranasal sinuses was seen in the third patient. Conclusion: Cranial nerve paralysis can be the presenting symptom of basal skull granulocytic sarcoma in children. Granulocytic sarcoma should be considered in the different diagnosis when diffuse abnormal signal intensities in the basal skull bone marrow with solitary or multiple soft tissue masses are shown on MRI. (authors)

  16. MRI findings of central nervous system granulocytic sarcoma (chloroma)

    International Nuclear Information System (INIS)

    Lee, Chang Man; Kim, Myung Soon; Kim, Ik Soo; Cho, Kwan Soo

    1997-01-01

    To characterize MRI findings of central nervous system (CNS) granulocytic sarcoma (chloroma) and to analyse the points which differentiate it from other CNS tumors. We evaluated MRI in six patients with CNS granulocytic sarcoma proven by surgery or bone marrow biopsy (intracranical, one case and spine five cases). A 0.5T superconductive MR machine was used for diagnosis and, axial, coronal and sagittal T1- and T2-weighted spin echo images and Gd-DTPA enhanced T1-weighted images were obtained. We retrospectively analized the location, signal intensity, margin, contrast enhancement and homogeneity, and bony change around the tumor. MRI findings of CNS granulocytic sarcomas were as follows : one tumor was seen to be an extra-axial mass in the posterior fossa of the brain, four were epidural, and one was an epidural and presacral masses in the spine;tumor magins were lobulated and three were smooth. On T1-weighted images, all tumors were of isoignal intensity;on T2-weighted images, four were of isosignal intersity and two were of high signal intensity. Contrast enhancement was inhomogeneous in five of six cases. Bony change around the tumor was seen in two cases. On T1-weighted images, CNS granulocytic sarcomas (chloromas) were of isosignal intensity, relative to brain parenchyma or spinal cord;on T2-weighted images, they were of iso or high signal intensity, with relative contrast enhancement. These points could be useful in differentiating them from other CNS tumors

  17. Efficient high-throughput molecular method to detect Ehrlichia ruminantium in ticks

    Directory of Open Access Journals (Sweden)

    Nídia Cangi

    2017-11-01

    Full Text Available Abstract Background Ehrlichia ruminantium is the causal agent of heartwater, a fatal tropical disease affecting ruminants with important economic impacts. This bacterium is transmitted by Amblyomma ticks and is present in sub-Saharan Africa, islands in the Indian Ocean and the Caribbean, where it represents a threat to the American mainland. Methods An automated DNA extraction method was adapted for Amblyomma ticks and a new qPCR targeting the pCS20 region was developed to improve E. ruminantium screening capacity and diagnosis. The first step in the preparation of tick samples, before extraction, was not automated but was considerably improved by using a Tissue Lyser. The new pCS20 Sol1 qPCR and a previously published pCS20 Cow qPCR were evaluated with the OIE standard pCS20 nested PCR. Results pCS20 Sol1 qPCR was found to be more specific than the nested PCR, with a 5-fold increase in sensitivity (3 copies/reaction vs 15 copies/reaction, was less prone to contamination and less time-consuming. As pCS20 Sol1 qPCR did not detect Rickettsia, Anasplasma and Babesia species or closely related species such as Panola Mountain Ehrlichia, E. chaffeensis and E. canis, its specificity was also better than Cow qPCR. In parallel, a tick 16S qPCR was developed for the quality control of DNA extraction that confirmed the good reproducibility of the automated extraction. The whole method, including the automated DNA extraction and pCS20 Sol1 qPCR, was shown to be sensitive, specific and highly reproducible with the same limit of detection as the combined manual DNA extraction and nested PCR, i.e. 6 copies/reaction. Finally, 96 samples can be tested in one day compared to the four days required for manual DNA extraction and nested PCR. Conclusions The adaptation of an automated DNA extraction using a DNA/RNA viral extraction kit for tick samples and the development of a new qPCR increased the accuracy of E. ruminantium epidemiological studies, as well as the

  18. Colorimetric detection of Ehrlichia canis via nucleic acid hybridization in gold nano-colloids.

    Science.gov (United States)

    Muangchuen, Ajima; Chaumpluk, Piyasak; Suriyasomboon, Annop; Ekgasit, Sanong

    2014-08-08

    Canine monocytic ehrlichiosis (CME) is a major thick-bone disease of dog caused by Ehrlichia canis. Detection of this causal agent outside the laboratory using conventional methods is not effective enough. Thus an assay for E. canis detection based on the p30 outer membrane protein gene was developed. It was based on the p30 gene amplification using loop-mediated isothermal DNA amplification (LAMP). The primer set specific to six areas within the target gene were designed and tested for their sensitivity and specificity. Detection of DNA signals was based on modulation of gold nanoparticles' surface properties and performing DNA/DNA hybridization using an oligonucleotide probe. Presence of target DNA affected the gold colloid nanoparticles in terms of particle aggregation with a plasmonic color change of the gold colloids from ruby red to purple, visible by the naked eye. All the assay steps were completed within 90 min including DNA extraction without relying on standard laboratory facilities. This method was very specific to target bacteria. Its sensitivity with probe hybridization was sufficient to detect 50 copies of target DNA. This method should provide an alternative choice for point of care control and management of the disease.

  19. Molecular detection of Anaplasma platys, Ehrlichia canis, Hepatozoon canis and Rickettsia monacensis in dogs from Maio Island of Cape Verde archipelago.

    Science.gov (United States)

    Lauzi, Stefania; Maia, João P; Epis, Sara; Marcos, Ricardo; Pereira, Cristina; Luzzago, Camilla; Santos, Marta; Puente-Payo, Pablo; Giordano, Alessia; Pajoro, Massimo; Sironi, Giuseppe; Faustino, Augusto

    2016-07-01

    Tick-borne diseases are emerging worldwide and have an important zoonotic relevance. Dogs play an important role in the epidemiology of several zoonotic tick-borne pathogens acting as sentinels and/or reservoirs. This study focused on the molecular identification of tick-borne pathogens in blood samples of 153 autochthonous asymptomatic dogs in Maio Island, Cape Verde archipelago. Eighty-four (54.9%) dogs were positive for one or more pathogens. Fifty-five (35.9%) dogs were infected with Hepatozoon canis, 53 (34.6%) with Anaplasma platys, five (3.3%) with Ehrlichia canis and Rickettsia monacensis, an emerging human pathogen, was also identified in a single dog (0.7%). The former three pathogens cause important canine tick-borne diseases that are transmitted or potentially transmitted by Rhipicephalus sanguineus s.l., the only hard tick identified in Cape Verde. Furthermore, Wolbachia spp. was amplified from the blood of one dog. None of the dogs were positive for Anaplasma phagocytophilum, Borrelia burgdorferi sensu lato, Midichloria mitochondrii, Bartonella spp., Babesia spp. or Theileria spp. Fifty-four (35.3%) animals showed single infections and 30 (19.6%) co-infections, with A. platys and H. canis co-infection being the most frequent (28 dogs, 18.3%). The frequency of E. canis infection was statistically different among age groups (P=0.017), being higher among dogs older than 4 years compared to younger dogs. Infection by A. platys was also statistically different among age groups (P=0.031), being higher in dogs younger than 2 years compared to older dogs. The statistical analyses showed no significant association of PCR positivity with gender or location. The frequency of tick-borne pathogens detected in dogs in Maio Island, including R. monacensis, highlights the need to improve diagnosis and control in order to prevent the risk of transmission of these pathogens among dogs and humans living in or travelling to this touristic island. Copyright © 2016

  20. Granulocytes enzymes as a biomarker of radiotoxicity in exposed workers

    International Nuclear Information System (INIS)

    Milacic, S.; Jovicic, D.; Tanaskovic, I.; Marinkovic, O.; Milacic, S.)

    2007-01-01

    When radionuclide reaches the organism it causes internal irradiation and the lesions may be long lasting in various tissues. Enzymes in leukocytes will be used as a biomarkers of contamination with radio-nuclide in nuclear medicine workers. The analysed group had been consisted of 74 workers, exposed to radioactive isotopes J 131 and mTc 99 in nuclear medicine. Duration of occupational exposure (DOE) varied, so the groups with DOE of 1-5, 6-15, and 16-30 years, were compared to one another. The control group consisted of 52 subjects exposed to radionuclides (Cs 137 ) from environmental. Alkaline phosphatases and myeloperoxidase activity were inhibited in the granulocytes. The neutrophilic granulocytes count was lower while the number of eosinophils was higher

  1. Case report 432: Granulocytic sarcoma (GS), with hypereosinophilic syndrome (HES)

    Energy Technology Data Exchange (ETDEWEB)

    Xipell, J M; Beamish, M R; Clark, D

    1987-07-01

    A case is presented of a 28-year-old man with a history of the hypereosinophilic syndrome, who subsequently developed granulocytic sarcoma of the tibia which proved resistant to aggressive therapy. He ultimately developed acute myeloid leukemia which also was resistant to therapy. The disease process was characterized by localised skeletal pain, the development of lytic lesions in several areas of the skeleton and progression to frank myeloid leukemia. (orig./SHA).

  2. Sweet's Syndrome Successfully Treated with Granulocyte and Monocyte Adsorption Apheresis

    OpenAIRE

    Fujii, Asami; Mizutani, Yoko; Hattori, Yuki; Takahashi, Tomoko; Ohnishi, Hidenori; Yoshida, Shozo; Seishima, Mariko

    2017-01-01

    Sweet’s syndrome is a neutrophilic dermatosis characterized by an abrupt onset of painful erythematous lesions showing neutrophilic infiltrates in the dermis. Fever and an elevated neutrophil level are generally observed. Sweet’s syndrome may be idiopathic, malignancy-associated, or drug-induced (mainly involving granulocyte colony-stimulating factor (G-CSF) administration). Although systemic corticosteroids are usually effective, the symptoms of Sweet’s syndrome recur in some refractory case...

  3. Prevalence of Ehrlichia canis, Anaplasma platys, Babesia canis vogeli, Hepatozoon canis, Bartonella vinsonii berkhoffii, and Rickettsia spp. in dogs from Grenada.

    Science.gov (United States)

    Yabsley, Michael J; McKibben, John; Macpherson, Calum N; Cattan, Peggy F; Cherry, Natalie A; Hegarty, Barbara C; Breitschwerdt, Edward B; O'Connor, Tom; Chandrashekar, Ramaswamy; Paterson, Tara; Perea, Marta Lanza; Ball, Geoffrey; Friesen, Stanley; Goedde, Jill; Henderson, Brooke; Sylvester, Wayne

    2008-02-14

    To identify the tick-borne pathogens in dogs from Grenada, we conducted a serologic survey for Ehrlichia canis in 2004 (104 dogs) and a comprehensive serologic and molecular survey for a variety of tick-borne pathogens in 2006 (73 dogs). In 2004 and 2006, 44 and 32 dogs (42.3% and 43.8%) were seropositive for E. canis, respectively. In 2006, several tick-borne pathogens were identified by serology and PCR. DNA of E. canis, Anaplasma platys, Babesia canis vogeli, Hepatozoon canis, and Bartonella sp. were identified in 18 (24.7%), 14 (19.2%), 5 (7%), 5 (7%), and 1 (1.4%) dogs, respectively. Six (8.2%) dogs were seropositive for Bartonella vinsonii subsp. berkhoffii. All dogs were seronegative and PCR-negative for Rickettsia spp. Coinfection with two or three pathogens was observed in eight dogs. Partial 16S rRNA E. canis and A. platys sequences were identical to sequences in GenBank. Partial 18S rRNA gene sequences from the Grenadian H. canis were identical to each other and had one possible mismatch (ambiguous base) from H. canis detected from Spain and Brazil. Grenadian B. c. vogeli sequences were identical to B. c. vogeli from Brazil and Japan. All of the detected pathogens are transmitted, or suspected to be transmitted, by Rhipicephalus sanguineus. Results of this study indicate that dogs from Grenada are infected with multiple tick-borne pathogens; therefore, tick-borne diseases should be included as differentials for dogs exhibiting thrombocytopenia, leukopenia, fever, or lethargy. One pathogen, E. canis, is also of potential public health significance.

  4. Recombination Is a Major Driving Force of Genetic Diversity in the Anaplasmataceae Ehrlichia ruminantium.

    Science.gov (United States)

    Cangi, Nídia; Gordon, Jonathan L; Bournez, Laure; Pinarello, Valérie; Aprelon, Rosalie; Huber, Karine; Lefrançois, Thierry; Neves, Luís; Meyer, Damien F; Vachiéry, Nathalie

    2016-01-01

    The disease, Heartwater, caused by the Anaplasmataceae E. ruminantium , represents a major problem for tropical livestock and wild ruminants. Up to now, no effective vaccine has been available due to a limited cross protection of vaccinal strains on field strains and a high genetic diversity of Ehrlichia ruminantium within geographical locations. To address this issue, we inferred the genetic diversity and population structure of 194 E. ruminantium isolates circulating worldwide using Multilocus Sequence Typing based on lipA, lipB, secY, sodB , and sucA genes . Phylogenetic trees and networks were generated using BEAST and SplitsTree, respectively, and recombination between the different genetic groups was tested using the PHI test for recombination. Our study reveals the repeated occurrence of recombination between E. ruminantium strains, suggesting that it may occur frequently in the genome and has likely played an important role in the maintenance of genetic diversity and the evolution of E. ruminantium . Despite the unclear phylogeny and phylogeography, E. ruminantium isolates are clustered into two main groups: Group 1 (West Africa) and a Group 2 (worldwide) which is represented by West, East, and Southern Africa, Indian Ocean, and Caribbean strains. Some sequence types are common between West Africa and Caribbean and between Southern Africa and Indian Ocean strains. These common sequence types highlight two main introduction events due to the movement of cattle: from West Africa to Caribbean and from Southern Africa to the Indian Ocean islands. Due to the long branch lengths between Group 1 and Group 2, and the propensity for recombination between these groups, it seems that the West African clusters of Subgroup 2 arrived there more recently than the original divergence of the two groups, possibly with the original waves of domesticated ruminants that spread across the African continent several thousand years ago.

  5. Intraoperative bleeding in dogs from Grenada seroreactive to Anaplasma platys and Ehrlichia canis.

    Science.gov (United States)

    Lanza-Perea, M; Zieger, U; Qurollo, B A; Hegarty, B C; Pultorak, E L; Kumthekar, S; Bruhl-Day, R; Breitschwerdt, E B

    2014-01-01

    Frequent exposure of Grenadian dogs to Rhipicephalus sanguineus results in Anaplasma platys, and Ehrlichia canis seroreactivity. During elective surgeries, substantial intraoperative hemorrhage occurs in some seroreactive dogs. To assess hemostatic parameters and bleeding tendencies as well as prevalence of PCR positivity in apparently healthy A. platys and E. canis seroreactive and seronegative free-roaming dogs from Grenada. Forty-seven elective surgery dogs allocated to 4 groups: Seronegative control (n = 12), A. platys (n = 10), E. canis (n = 14) and A. platys, and E. canis (n = 11) seroreactive. Preoperatively, hemostasis was assessed by platelet count, prothrombin time, activated partial thromboplastin time, and buccal mucosal bleeding time. Intra- and postoperative bleeding scores were subjectively assigned. Blood, spleen, bone marrow, and lymph node aspirates were tested by PCR. Bleeding scores in dogs coseroreactive for A. platys and E. canis were higher (P = .015) than those of seronegative dogs. A. platys DNA was amplified from 7/21 (33%) A. platys seroreactive dogs and from 1 E. canis seroreactive dog; E. canis DNA was amplified from 21/25 (84%) E. canis seroreactive dogs. E. canis DNA was amplified most often from blood, whereas A. platys DNA was amplified most often from bone marrow. Apparently healthy, free-roaming dogs coseropositive for A. platys and E. canis may have increased intraoperative bleeding tendencies despite normal hemostatic parameters. Future investigations should explore the potential for vascular injury as a cause for bleeding in these dogs. Improved tick control is needed for dogs in Grenada. Copyright © 2014 by the American College of Veterinary Internal Medicine.

  6. Pathological manifestations in lymphatic filariasis correlate with lack of inhibitory properties of IgG4 antibodies on IgE-activated granulocytes.

    Science.gov (United States)

    Prodjinotho, Ulrich F; von Horn, Charlotte; Debrah, Alex Y; Batsa Debrah, Linda; Albers, Anna; Layland, Laura E; Hoerauf, Achim; Adjobimey, Tomabu

    2017-07-01

    Helminth parasites are known to be efficient modulators of their host's immune system. To guarantee their own survival, they induce alongside the classical Th2 a strong regulatory response with high levels of anti-inflammatory cytokines and elevated plasma levels of IgG4. This particular antibody was shown in different models to exhibit immunosuppressive properties. How IgG4 affects the etiopathology of lymphatic filariasis (LF) is however not well characterized. Here we investigate the impact of plasma and affinity-purified IgG/IgG4 fractions from endemic normals (EN) and LF infected pathology patients (CP), asymptomatic microfilaraemic (Mf+) and amicrofilaraemic (Mf-) individuals on IgE/IL3 activated granulocytes. The activation and degranulation states were investigated by monitoring the expression of CD63/HLADR and the release of granule contents (neutrophil elastase (NE), eosinophil cationic protein (ECP) and histamine) respectively by flow cytometry and ELISA. We could show that the activation of granulocytes was inhibited in the presence of plasma from EN and Mf+ individuals whereas those of Mf- and CP presented no effect. This inhibitory capacity was impaired upon depletion of IgG in Mf+ individuals but persisted in IgG-depleted plasma from EN, where it strongly correlated with the expression of IgA. In addition, IgA-depleted fractions failed to suppress granulocyte activation. Strikingly, affinity-purified IgG4 antibodies from EN, Mf+ and Mf- individuals bound granulocytes and inhibited activation and the release of ECP, NE and histamine. In contrast, IgG4 from CP could not bind granulocytes and presented no suppressive capacity. Reduction of both the affinity to, and the suppressive properties of anti-inflammatory IgG4 on granulocytes was reached only when FcγRI and II were blocked simultaneously. These data indicate that IgG4 antibodies from Mf+, Mf- and EN, in contrast to those of CP, natively exhibit FcγRI/II-dependent suppressive properties on

  7. Neutrophilic granulocytes reactive response in candida vulvovaginitis patients with intracellular microorganism persistence complications

    OpenAIRE

    YAKOVYCHUK NINA DMYTRIVNA; DJUIRIAK VALENTYNA STEPANIVNA

    2015-01-01

    Polymorphic neutrophilic granulocytes reactive response and body immune reactivity in general considerably decrease in patients suffering from candida vaginitis on the basis of intracellular microorganisms persistence.

  8. Characterization of buffy coat-derived granulocytes for clinical use: a comparison with granulocyte colony-stimulating factor/dexamethasone-pretreated donor-derived products.

    Science.gov (United States)

    van de Geer, A; Gazendam, R P; Tool, A T J; van Hamme, J L; de Korte, D; van den Berg, T K; Zeerleder, S S; Kuijpers, T W

    2017-02-01

    Buffy coat-derived granulocytes have been described as an alternative to the apheresis product from donors pretreated with dexamethasone and granulocyte colony-stimulating factor (G-CSF). The latter is - dependent on the local and national settings - obtained following a demanding and time-consuming procedure, which is undesirable in critically ill septic patients. In contrast, buffy coat-derived products have a large volume and are often heavily contaminated with red cells and platelets. We developed a new pooled buffy coat-derived product with high purity and small volume, and performed a comprehensive functional characterization of these granulocytes. We pooled ten buffy coats following the production of platelet concentrates. Saline 0·9% was added to decrease the viscosity and the product was split into plasma, red cells and a 'super' buffy coat. Functional data of the granulocytes were compared to those obtained with granulocytes from healthy controls and G-CSF/dexamethasone-pretreated donors. Buffy coat-derived granulocytes showed adhesion, chemotaxis, reactive oxygen species production, degranulation, NETosis and in vitro killing of Staphylococcus aureus, Escherichia coli and Aspergillus species comparable to control and G-CSF/dexamethasone-derived granulocytes. Candida killing was superior compared to G-CSF/dexamethasone-derived granulocytes. Immunophenotyping was normal; especially no signs of activation in the buffy coat-derived granulocytes were seen. Viability was reduced. Buffy coats are readily available in the regular blood production process and would take away the concerns around the apheresis product. The product described appears a promising alternative for transfusion purposes. © 2017 International Society of Blood Transfusion.

  9. Vaccination with an Attenuated Mutant of Ehrlichia chaffeensis Induces Pathogen-Specific CD4+ T Cell Immunity and Protection from Tick-Transmitted Wild-Type Challenge in the Canine Host.

    Directory of Open Access Journals (Sweden)

    Jodi L McGill

    Full Text Available Ehrlichia chaffeensis is a tick-borne rickettsial pathogen and the causative agent of human monocytic ehrlichiosis. Transmitted by the Amblyomma americanum tick, E. chaffeensis also causes disease in several other vertebrate species including white-tailed deer and dogs. We have recently described the generation of an attenuated mutant strain of E. chaffeensis, with a mutation in the Ech_0660 gene, which is able to confer protection from secondary, intravenous-administered, wild-type E. chaffeensis infection in dogs. Here, we extend our previous results, demonstrating that vaccination with the Ech_0660 mutant protects dogs from physiologic, tick-transmitted, secondary challenge with wild-type E. chaffeensis; and describing, for the first time, the cellular and humoral immune responses induced by Ech_0660 mutant vaccination and wild-type E. chaffeensis infection in the canine host. Both vaccination and infection induced a rise in E. chaffeensis-specific antibody titers and a significant Th1 response in peripheral blood as measured by E. chaffeensis antigen-dependent CD4+ T cell proliferation and IFNγ production. Further, we describe for the first time significant IL-17 production by peripheral blood leukocytes from both Ech_0660 mutant vaccinated animals and control animals infected with wild-type E. chaffeensis, suggesting a previously unrecognized role for IL-17 and Th17 cells in the immune response to rickettsial pathogens. Our results are a critical first step towards defining the role of the immune system in vaccine-induced protection from E. chaffeensis infection in an incidental host; and confirm the potential of the attenuated mutant clone, Ech_0660, to be used as a vaccine candidate for protection against tick-transmitted E. chaffeensis infection.

  10. Successful treatment of fusarium solani ecthyma gangrenosum in a patient affected by leukocyte adhesion deficiency type 1 with granulocytes transfusions

    Directory of Open Access Journals (Sweden)

    Hassen Assia

    2010-10-01

    Full Text Available Abstract Background Ecthyma gangrenosum (EG manifests as a skin lesion affecting patients suffering extreme neutropenia and is commonly associated with Pseudomonas aeruginosa in immunocompromised patients. Leukocyte adhesion deficiency I (LAD I which count among primary immunodeficiency syndromes of the innate immunity, is an autosomal recessive disorder characterized in its severe phenotype by a complete defect in CD18 expression on neutrophils, delayed cord separation, chronic skin ulcers mainly due to recurrent bacterial and fungal infections, leucocytosis with high numbers of circulating neutrophils and an accumulation of abnormally low number of neutrophils at sites of infection. Case Presentation We report at our knowledge the first case of a child affected by LAD-1, who experienced during her disease course a multi-bacterial and fungal EG lesion caused by fusarium solani. Despite targeted antibiotics and anti-fungi therapy, the lesion extended for as long as 18 months and only massive granulocytes pockets transfusions in association with G-CSF had the capacity to cure this lesion. Conclusion We propose that granulocytes pockets transfusions will be beneficial to heal EG especially in severely immunocompromised patients.

  11. Detection of Rickettsia and Ehrlichia spp. in Ticks Associated with Exotic Reptiles and Amphibians Imported into Japan.

    Science.gov (United States)

    Andoh, Masako; Sakata, Akiko; Takano, Ai; Kawabata, Hiroki; Fujita, Hiromi; Une, Yumi; Goka, Koichi; Kishimoto, Toshio; Ando, Shuji

    2015-01-01

    One of the major routes of transmission of rickettsial and ehrlichial diseases is via ticks that infest numerous host species, including humans. Besides mammals, reptiles and amphibians also carry ticks that may harbor Rickettsia and Ehrlichia strains that are pathogenic to humans. Furthermore, reptiles and amphibians are exempt from quarantine in Japan, thus facilitating the entry of parasites and pathogens to the country through import. Accordingly, in the current study, we examined the presence of Rickettsia and Ehrlichia spp. genes in ticks associated with reptiles and amphibians originating from outside Japan. Ninety-three ticks representing nine tick species (genera Amblyomma and Hyalomma) were isolated from at least 28 animals spanning 10 species and originating from 12 countries (Ghana, Jordan, Madagascar, Panama, Russia, Sri Lanka, Sudan, Suriname, Tanzania, Togo, Uzbekistan, and Zambia). None of the nine tick species are indigenous in Japan. The genes encoding the common rickettsial 17-kDa antigen, citrate synthase (gltA), and outer membrane protein A (ompA) were positively detected in 45.2% (42/93), 40.9% (38/93), and 23.7% (22/93) of the ticks, respectively, by polymerase chain reaction (PCR). The genes encoding ehrlichial heat shock protein (groEL) and major outer membrane protein (omp-1) were PCR-positive in 7.5% (7/93) and 2.2% (2/93) of the ticks, respectively. The p44 gene, which encodes the Anaplasma outer membrane protein, was not detected. Phylogenetic analysis showed that several of the rickettsial and ehrlichial sequences isolated in this study were highly similar to human pathogen genes, including agents not previously detected in Japan. These data demonstrate the global transportation of pathogenic Rickettsia and Ehrlichia through reptile- and amphibian-associated ticks. These imported animals have potential to transfer pathogens into human life. These results highlight the need to control the international transportation of known and

  12. Detection of Rickettsia and Ehrlichia spp. in Ticks Associated with Exotic Reptiles and Amphibians Imported into Japan.

    Directory of Open Access Journals (Sweden)

    Masako Andoh

    Full Text Available One of the major routes of transmission of rickettsial and ehrlichial diseases is via ticks that infest numerous host species, including humans. Besides mammals, reptiles and amphibians also carry ticks that may harbor Rickettsia and Ehrlichia strains that are pathogenic to humans. Furthermore, reptiles and amphibians are exempt from quarantine in Japan, thus facilitating the entry of parasites and pathogens to the country through import. Accordingly, in the current study, we examined the presence of Rickettsia and Ehrlichia spp. genes in ticks associated with reptiles and amphibians originating from outside Japan. Ninety-three ticks representing nine tick species (genera Amblyomma and Hyalomma were isolated from at least 28 animals spanning 10 species and originating from 12 countries (Ghana, Jordan, Madagascar, Panama, Russia, Sri Lanka, Sudan, Suriname, Tanzania, Togo, Uzbekistan, and Zambia. None of the nine tick species are indigenous in Japan. The genes encoding the common rickettsial 17-kDa antigen, citrate synthase (gltA, and outer membrane protein A (ompA were positively detected in 45.2% (42/93, 40.9% (38/93, and 23.7% (22/93 of the ticks, respectively, by polymerase chain reaction (PCR. The genes encoding ehrlichial heat shock protein (groEL and major outer membrane protein (omp-1 were PCR-positive in 7.5% (7/93 and 2.2% (2/93 of the ticks, respectively. The p44 gene, which encodes the Anaplasma outer membrane protein, was not detected. Phylogenetic analysis showed that several of the rickettsial and ehrlichial sequences isolated in this study were highly similar to human pathogen genes, including agents not previously detected in Japan. These data demonstrate the global transportation of pathogenic Rickettsia and Ehrlichia through reptile- and amphibian-associated ticks. These imported animals have potential to transfer pathogens into human life. These results highlight the need to control the international transportation of known

  13. In Vitro Activities of Telithromycin (HMR 3647) against Rickettsia rickettsii, Rickettsia conorii, Rickettsia africae, Rickettsia typhi, Rickettsia prowazekii, Coxiella burnetii, Bartonella henselae, Bartonella quintana, Bartonella bacilliformis, and Ehrlichia chaffeensis

    OpenAIRE

    Rolain, Jean-Marc; Maurin, Max; Bryskier, André; Raoult, Didier

    2000-01-01

    In vitro activities of telithromycin compared to those of erythromycin against Rickettsia spp., Bartonella spp., Coxiella burnetii, and Ehrlichia chaffeensis were determined. Telithromycin was more active than erythromycin against Rickettsia, Bartonella, and Coxiella burnetii, with MICs of 0.5 μg/ml, 0.003 to 0.015 μg/ml, and 1 μg/ml, respectively, but was inactive against Ehrlichia chaffeensis.

  14. 99Tcsup(m)-HMPAO labelled leucocytes: comparison with 111In-tropolonate labelled granulocytes

    International Nuclear Information System (INIS)

    Peters, A.M.; Roddie, M.E.; Zacharopoulos, G.P.; George, P.; Stuttle, A.W.J.; Lavender, J.P.; Danpure, H.J.; Osman, S.

    1988-01-01

    The lipophilic complex, 99 Tcsup(m)-hexamethylpropyleneamine oxime (HMPAO) is an efficient leucocyte label, and labels granulocytes with more stability than mononuclear leucocytes. The recovery of 99 Tcsup(m)-HMPAO granulocytes was similar to 111 In-labelled granulocytes isolated and labelled in plasma using tropolone. The Tsub(1/2) of 99 Tcsup(m)-HMPAO labelled granulocytes in blood was less than that of 111 In-labelled granulocytes. The initial biodistribution of 99 Tcsup(m)-labelled leucocytes was similar to 111 In-labelled granulocytes, with a rapid initial lung transit, prominent splenic activity, bone marrow activity and minimal hepatic activity, although, unlike 111 In, 99 Tcsup(m) activity was also seen in urine, occasionally in the gallbladder, and, from about 4 h, consistently in the colon. Bone marrow activity was particularly prominent with 99 Tcsup(m). About 6% of 99 Tcsup(m) was excreted in the faeces up to 48 h after injection, and about 17% in urine up to 24 h. The time-activity curves of reticuloendothelial activity up to 24 h were broadly similar for the two labelled cell preparations. Clinical information given by the two agents was similar in 27 of 30 patients who received both. We conclude that with respect to granulocyte kinetics and clinical data, 99 Tcsup(m)-HMPAO labelled leucocytes are comparable with 111 In-tropolonate labelled granulocytes. (author)

  15. A karyometric note on nucleoli in human early granulocytic precursors.

    Science.gov (United States)

    Smetana, K; Mikulenková, D; Jirásková, I; Klamová, H

    2006-01-01

    The diameter of nucleoli was measured in human bone marrow early granulocytic precursors after visualization by a simple cytochemical method for demonstration of RNA. Such method facilitated to clearly see nucleolar bodies without perinucleolar chromatin, including those of micronucleoli. The bone marrow of patients suffering from chronic myeloid leukaemia (untreated with cytostatics) provided a satisfactory number of both myeloblasts and promyelocytes for nucleolar measurements because of prevailing granulopoiesis. The direct nucleolar measurement was carried out on digitized and processed images on the screen at magnification 4,300x. It seems to be likely that the nucleolar size is directly related to the number of nucleoli per cell. The largest nucleoli were present in both myeloblasts and promyelocytes that possessed a single nucleolus. In contrast, the nucleolar diameter was significantly smaller in cells with multiple nucleoli. However, in cells with small multiple nucleoli, one of them was always larger and dominant with a large number of AgNORs. Such large nucleoli are possibly visible in specimens stained with panoptic procedures or methods staining nuclear chromatin or DNA. It should also be mentioned that both myeloblasts and promyelocytes mostly possessed two nucleoli with the mean diameter close to 1.5 microm. The incidence of early granulocytic precursors classified according to the nucleolar number and size strongly suggested that the various nucleolar number and nucleolar size in these cells might be related to the different stage of the cell cycle and might also explain their heterogeneity.

  16. Infection,

    Science.gov (United States)

    1980-10-16

    characteristic in severe gram-negative sepsis. Hypertriglyceridemia results from an increase in hepatic synthesis in combination with diminished activity of...induced stress, and tissue repair (1). The magnitude and type of nutritional losses caused by an infection reflect both the severity and duration of an... several functional forms of nutrient loss must be anticipated. Functional losses are defined as the within-body losses of nutrients due to infection

  17. Study of cross-reactivity in serum samples from dogs positive for Leishmania sp., Babesia canis and Ehrlichia canis in enzyme-linked immunosorbent assay and indirect fluorescent antibody test Estudo da reatividade cruzada em amostras de soro de cães positivos para Leishmania sp., Babesia canis e Ehrlichia canis, pelo ensaio imunoenzimático indireto e pela reação de imunofluorescência indireta

    Directory of Open Access Journals (Sweden)

    Trícia Maria F. de Sousa Oliveira

    2008-03-01

    Full Text Available To verify the presence of cross-reaction among leishmaniosis, ehrlichiosis and babesiosis in serological diagnostics used in human visceral leishmaniasis control programs, serum samples from leishmaniasis endemic and non-endemic areas were collected and tested by Indirect Fluorescent Antibody (IFAT and Enzyme-linked immunosorbent assay (ELISA. All serum samples from endemic areas were positive for Leishmania sp., by ELISA and IFAT, 51% positive for Babesia canis and 43% for Ehrlichia canis by IFAT. None of the serum samples from non-endemic areas were positive for Leishmania sp., by IFAT, but 67% were positive for B. canis and 78% for E. canis using the same test. When tested by ELISA for Leishmania sp., four samples from non-endemic area were positive. These dogs were then located and no clinical signs, parasites or antibody was detected in new tests for a six month period. Only one of these 4 samples was positive for B. canis by IFAT and ELISA and three for E. canis by IFAT. The results of the work suggest a co-infection in the endemic area and no serological cross-reaction among these parasites by IFAT and ELISA.Para verificar a existência de reação cruzada entre leishmaniose visceral, erliquiose e babesiose, nos testes sorológicos utilizados em programas de controle da leishmaniose visceral humana, amostras de soro canino provenientes de áreas endêmicas e não endêmicas para essa enfermidade, foram testadas pela Reação de Imunofluorescência (RIFI e Ensaio imunoenzimático (ELISA. Todos os soros provenientes de área endêmica foram positivos para Leishmania sp pelo ELISA e RIFI, 51% para Babesia canis e 43% para Ehrlichia canis pela RIFI. Pela RIFI, nenhum dos soros provenientes de área não endêmica foi positivo para Leishmania sp, sendo 67% positivos para B. canis e 78% para E. canis pelo mesmo teste. Quando testados pelo ELISA para Leishmania sp., quatro soros da área não endêmica foram positivos. Os cães foram localizados

  18. Generation of dendritic cells for immunotherapy is minimally impaired by granulocytes in the monocyte preparation.

    Science.gov (United States)

    ten Brinke, Anja; Karsten, Miriam L; Dieker, Miranda C; Zwaginga, Jaap Jan; Vrielink, Hans; Marieke van Ham, S

    2006-01-01

    The growing number of clinical studies, using monocyte-derived DC therapy, requires protocols where a sufficient number of dendritic cell (DCs) are produced according to current Good Manufacturing Practice guidelines. Therefore, a closed culture system for the generation of DCs is inevitable. One cost-effective way to isolate monocytes directly from leukapheresis material in a closed system is by elutriation with the Elutra cell separation system. In the Elutra, granulocytes co-purify with the monocytes. Therefore, we studied if and to what extent the presence of granulocytes in a monocyte product affects the generation of mature DCs. The presence of up to 16% granulocytes in the monocyte product had no significant effects on the quality of the DCs formed. The presence of higher granulocyte percentages, however, gradually altered DC quality. In this respect, the presence of higher number of granulocytes induced significant lower migratory capacity of the DCs and lower expression levels of CD80, CD40 and CD86. No effects were observed on the DC yield, cytokine production or the stimulatory capacity of the DCs in MLR. In conclusion, the presence of 20-30% granulocytes in a monocyte product has no major influence on the quality of the DCs generated from monocytes. Therefore, the Elutra is a suitable closed system apparatus to separate monocytes from other blood components for the generation of DCs, even from leukapheresis material which contains a high number of granulocytes.

  19. Pre leukemic granulocytic sarcoma of vagina: a case report with review of literature

    International Nuclear Information System (INIS)

    Lakshminarasimhan, Srinivasan; Doval, D.C.; Rajashekhar, Usha; Mukherjee, Geethashree; Kannan, V.; Lakshmi Devi; Bapsy, P.P.

    1996-01-01

    Granulocytic sarcoma is an extramedullary tumor of malignant granulocytic progenitor cells, that may precede the onset of acute myeloid leukemia or appear during the leukemic manifestation or blastic crisis of chronic myeloproliferative disorders. A case of granulocytic sarcoma of vagina in a 27 year old woman treated with local radiotherapy is described. After seven months of follow up she developed acute myeloid leukemia. The case has been presented in view of its rarity and discussed in light of the available literature. (author). 13 refs., 1 fig

  20. Co-infection with arthropod-borne pathogens in domestic cats.

    Science.gov (United States)

    André, Marcos Rogério; Filgueira, Kilder Dantas; Calchi, Ana Cláudia; Sousa, Keyla Carstens Marques de; Gonçalves, Luiz Ricardo; Medeiros, Vitor Brasil; Ximenes, Poliana Araújo; Lelis, Ivana Cristina Nunes Gadelha; Meireles, Maria Vanuza Nunes de; Machado, Rosangela Zacarias

    2017-01-01

    The role of several feline vector-borne pathogens (FVBP) as a cause of disease in cats has not been clearly determined. In fact, with the exception of Bartonella spp. and hemoplasmas, FVBP in cats has not been clearly determined in Brazil yet. The present study aimed at identifying, by using molecular methods, the presence of FVBP in three cats showing non-specific clinical signs and inclusions suggestive of hemoparasites in blood smears. Cytauxzoon felis, 'Candidatus Mycoplasma haemominutum', Ehrlichia sp. closely related to Ehrlichia canis, and Anaplasma sp. closely related to Anaplasma phagocytophilum were detected in blood samples from two out of three sampled cats. Both cats positive for multiple FVBP did not show hematological and biochemical abnormalities. The present work emphasizes the need for molecular confirmation of co-infection by multiple FVBP in cats presenting non-specific clinical signs and inclusions resembling hemoparasites in blood smears.

  1. Co-infection with arthropod-borne pathogens in domestic cats

    Directory of Open Access Journals (Sweden)

    Marcos Rogério André

    2017-11-01

    Full Text Available Abstract The role of several feline vector-borne pathogens (FVBP as a cause of disease in cats has not been clearly determined. In fact, with the exception of Bartonella spp. and hemoplasmas, FVBP in cats has not been clearly determined in Brazil yet. The present study aimed at identifying, by using molecular methods, the presence of FVBP in three cats showing non-specific clinical signs and inclusions suggestive of hemoparasites in blood smears. Cytauxzoon felis, ‘Candidatus Mycoplasma haemominutum’, Ehrlichia sp. closely related to Ehrlichia canis, and Anaplasma sp. closely related to Anaplasma phagocytophilum were detected in blood samples from two out of three sampled cats. Both cats positive for multiple FVBP did not show hematological and biochemical abnormalities. The present work emphasizes the need for molecular confirmation of co-infection by multiple FVBP in cats presenting non-specific clinical signs and inclusions resembling hemoparasites in blood smears.

  2. Soroprevalência de anticorpos anti-Ehrlichia canis em cães de Cuiabá, Mato Grosso Seroprevalence anti-Ehrlichia canis antibodies in dogs of Cuiabá, Mato Grosso

    Directory of Open Access Journals (Sweden)

    José Nivaldo da Silva

    2010-06-01

    Full Text Available A erliquiose canina é uma doença transmitida por carrapatos Rhipicephalus sanguineus e ocasionada pela Ehrlichia canis, bactéria intracelular obrigatória. O presente estudo verificou a prevalência de anticorpos anti-E. canis em 254 cães de quatro regiões administrativas de Cuiabá, Estado de Mato Grosso, por imunofluorescência indireta, observando-se uma prevalência de 42,5% (108/254 sem diferença significativa entre as regiões. As variáveis idade, raça, sexo, hábitat, acesso à zona rural e presença de carrapatos foram analisadas. Os títulos de anticorpos variaram entre 1:40 a 1:2.560. Somente 32 (29,63% cães soropositivos estavam infestados por carrapatos, todos R. sanguineus. O resultado encontrado confirma que não há predisposição racial, sexual ou etária, enquanto a menor ocorrência de cães reagentes no intradomicílio provavelmente está relacionada à baixa infestação por carrapato, apesar de não ter sido observada diferença significativa entre os cães com ou sem a infestação com o carrapato vetor.Canine ehrlichiosis is a disease transmitted by ticks Rhipicephalus sanguineus and caused by Ehrlichia canis, obligatory intracellular bacteria. The present study examined the prevalence of anti-E. canis in 254 dogs from four administrative regions of Cuiabá, Mato Grosso, by indirect immunofluorescence assay. There was a prevalence of 42.5% (108/254 without significant difference between the studied regions. The variables age, breed, sex, habitat, access to rural and ticks were analyzed. The antibody titers ranged from 1:40 to 1:2,560. Only 32 (29.63% seropositive dogs were infested with ticks, all R. sanguineus. The results confirm that do not have breed, sex or age predisposition to ehrlichiosis due E. canis, while the lowest occurrence of reactive dogs indoors probably related to low tick infestation, although no significant difference between dogs with or without infestation with the tick vector.

  3. Comparison of simultaneous splenic sample PCR with blood sample PCR for diagnosis and treatment of experimental Ehrlichia canis infection.

    Science.gov (United States)

    Harrus, Shimon; Kenny, Martin; Miara, Limor; Aizenberg, Itzhak; Waner, Trevor; Shaw, Susan

    2004-11-01

    This report presents evidence that dogs recover from acute canine monocytic ehrlichiosis (CME) after 16 days of doxycycline treatment (10 mg/kg of body weight every 24 h). Blood PCR was as valuable as splenic aspirate PCR for early diagnosis of acute CME. Splenic aspirate PCR was, however, superior to blood PCR for the evaluation of ehrlichial elimination.

  4. Granulocytic sarcoma in a patient with chronic myeloid leukaemia in complete haematological, cytogenetic and molecular remission.

    Science.gov (United States)

    Kittai, Adam; Yu, Eun-Mi; Tabbara, Imad

    2014-12-23

    Granulocytic sarcoma, also known as myeloid sarcoma, is an extramedullary tumour composed of immature myeloid cells. Granulocytic sarcoma is typically found in patients with acute myeloid leukaemia, accelerated phase or blast crisis of chronic myeloid leukaemia, myelodysplastic syndrome, or as an isolated event without bone marrow involvement. We present a case of granulocytic sarcoma in a patient with chronic myeloid leukaemia in the setting of complete haematological, molecular and cytogenetic remission. Our patient was first treated with imatinib for chronic-phase chronic myeloid leukaemia. After maintaining remission for 42 months, he developed a granulocytic sarcoma in his spine. In this case report, we describe our case, along with the three other cases reported in the literature. In addition to being a rare diagnosis, this case demonstrates the importance of being vigilant in diagnosing the cause of back pain and atypical symptoms in patients with a history of leukaemia. 2014 BMJ Publishing Group Ltd.

  5. Modulation of oxygen-dependent and oxygen-independent metabolism of neutrophilic granulocytes by quantum points.

    Science.gov (United States)

    Pleskova, S N; Mikheeva, E R

    2011-08-01

    Inhibition of neutrophilic granulocyte metabolism under the effect of semiconductor quantum points was demonstrated. The status of the oxidative system was evaluated by the NBT test, nonoxidative status by the lysosomal cationic test. It was found that quantum points in a dose of 0.1 mg/ml irrespective of their core and composition of coating significantly inhibited oxygen-dependent and oxygen-independent metabolism of neutrophilic granulocytes.

  6. Granulocytic Sarcoma in a Nonleukemic Patient: Place of Radiotherapy and Systemic Therapies

    Directory of Open Access Journals (Sweden)

    C. Chargari

    2011-01-01

    Full Text Available Granulocytic sarcoma is a rare extramedullary tumour, which most often occurs in the course of an acute or chronic leukaemia or myeloproliferative disorders. Rarely it is found before peripheral blood or bone marrow evidence of leukemia is present. We report an unusual case of acute paraplegia at first presentation of a spinal epidural granulocytic sarcoma without any haematological disorder. Therapeutic strategies are discussed in the light of the literature.

  7. Vitamin E--a selective inhibitor of the NADPH oxidoreductase enzyme system in human granulocytes

    International Nuclear Information System (INIS)

    Butterick, C.J.; Baehner, R.L.; Boxer, L.A.; Jersild, R.A. Jr.

    1983-01-01

    The cellular sites of H 2 O 2 formation in phagocytizing granulocytes have been identified with cerium chloride. A precipitate was visible in phagosomes and on plasma membranes from intact normal cells in the presence of either 0.71 mM NADH or NADPH. X-ray microanalysis permitted identification of cerium deposition within the phagosomes even in the absence of reduced pyridine nucleotides. Catalase ablated the formation of the reaction product. Intact granulocytes obtained from subjects receiving 1600 units of vitamin E daily for 2 weeks exhibited reaction product in the presence of NADH but not NADPH. Intact cells from subjects treated with vitamin E demonstrated diminished numbers of phagocytic vesicles containing reaction product. During phagocytosis the granulocytes treated with vitamin E consumed oxygen but exhibited significantly reduced rates of hydrogen-peroxide-dependent glucose-1- 14 C oxidation to 14 CO 2 . Isolated phagocytic vesicles obtained from granulocytes after ingestion of opsonized lipopolysaccharide-paraffin oil droplets contained reaction product when exposed to 0.71 mM NADPH. No reaction product was evident at 0.71 mM NADH but was evident at 2.0 mM NADH. Isolated phagocytic vesicles from the granulocytes of subjects receiving vitamin E exhibited reaction product only in the presence of NADH. These observations suggest that vitamin E interferes with the electron transport chain apparently required for the oxidation of NADPH to form H 2 O 2 in the phagocytizing granulocyte

  8. Tissue-transglutaminase contributes to neutrophil granulocyte differentiation and functions.

    Science.gov (United States)

    Balajthy, Zoltán; Csomós, Krisztián; Vámosi, György; Szántó, Attila; Lanotte, Michel; Fésüs, László

    2006-09-15

    Promyelocytic NB4 leukemia cells undergo differentiation to granulocytes following retinoic acid treatment. Here we report that tissue transglutaminase (TG2), a protein cross-linking enzyme, was induced, then partially translocated into the nucleus, and became strongly associated with the chromatin during the differentiation process. The transglutaminase-catalyzed cross-link content of both the cytosolic and the nuclear protein fractions increased while NB4 cells underwent cellular maturation. Inhibition of cross-linking activity of TG2 by monodansylcadaverin in these cells led to diminished nitroblue tetrazolium (NBT) positivity, production of less superoxide anion, and decreased expression of GP91PHOX, the membrane-associated subunit of NADPH oxidase. Neutrophils isolated from TG2(-/-) mice showed diminished NBT reduction capacity, reduced superoxide anion formation, and down-regulation of the gp91phox subunit of NADPH oxidase, compared with wild-type cells. It was also observed that TG2(-/-) mice exhibited increased neutrophil phagocytic activity, but had attenuated neutrophil chemotaxis and impaired neutrophil extravasation with higher neutrophil counts in their circulation during yeast extract-induced peritonitis. These results clearly suggest that TG2 may modulate the expression of genes related to neutrophil functions and is involved in several intracellular and extracellular functions of extravasating neutrophil.

  9. Granulocyte-associated IgG in neutropenic disorders

    International Nuclear Information System (INIS)

    Cines, D.B.; Passero, F.; Guerry, D.; Bina, M.; Dusak, B.; Schreiber, A.D.

    1982-01-01

    We applied a radiolabeled antiglobulin test to a study of patients with a variety of neutropenic disorders. After defining the nature of the interaction of radiolabeled anti-IgG with the neutrophil, we studied 16 patients with neutropenia of uncertain etiology and adequate bone marrow granulocyte precursors. Twelve of these 16 patients had increased neutrophil-associated IgG (PMN-IgG). Patients with the highest levels of PMN-IgG had the lowest neutrophil counts. The majority of patients with neutropenia and increased PMN-IgG had an underlying immunologic disorder that included immune thrombocytopenic purpura in 5 patients and autoimmune hemolytic anemia in 1 patient. In some patients, elevated PMN-IgG preceded other evidence for immunologic disease. The direct antiglobulin test helped to distinguish neutropenic patients with increased PMN-IgG both from patients with neutropenia due to a known nonimmune disorder and from nonneutropenic patients with rheumatoid arthritis or systemic lupus erythematosis. Each of four patients with increased neutrophil-associated IgG treated with systemic corticosteroids responded clinically with an associated fall in neutrophil IgG and a rise in the circulating neutrophil count. The radiolabeled antiglobulin test appears useful in defining a subpopulation of patients with neutropenia due to an underlying immunologic disorder

  10. Granulocyte colony-stimulating factor induces in vitro lymphangiogenesis

    International Nuclear Information System (INIS)

    Lee, Ae Sin; Kim, Dal; Wagle, Susbin Raj; Lee, Jung Eun; Jung, Yu Jin; Kang, Kyung Pyo; Lee, Sik; Park, Sung Kwang; Kim, Won

    2013-01-01

    Highlights: •G-CSF induces tube formation, migration and proliferation of lymphatic cells. •G-CSF increases phosphorylation of MAPK and Akt in lymphatic endothelial cells. •MAPK and Akt pathways are linked to G-CSF-induced in vitro lymphangiogenesis. •G-CSF increases sprouting of a lymphatic ring. •G-CSF produces peritoneal lymphangiogenesis. -- Abstract: Granulocyte-colony stimulating factor (G-CSF) is reported to induce differentiation in cells of the monocyte lineage and angiogenesis in vascular endothelial cells, but its effects on lymphangiogenesis is uncertain. Here we examined the effects and the mechanisms of G-CSF-induced lymphangiogenesis using human lymphatic endothelial cells (hLECs). Our results showed that G-CSF induced capillary-like tube formation, migration and proliferation of hLECs in a dose- and time-dependent manner and enhanced sprouting of thoracic duct. G-CSF increased phosphorylation of Akt and ERK1/2 in hLECs. Supporting the observations, specific inhibitors of phosphatidylinositol 3′-kinase and MAPK suppressed the G-CSF-induced in vitro lymphangiogenesis and sprouting. Intraperitoneal administration of G-CSF to mice also stimulated peritoneal lymphangiogenesis. These findings suggest that G-CSF is a lymphangiogenic factor

  11. Exercise increases lactoferrin, but decreases lysozyme in salivary granulocytes.

    Science.gov (United States)

    Gillum, Trevor; Kuennen, Matthew; McKenna, Zachary; Castillo, Micaela; Jordan-Patterson, Alex; Bohnert, Caitlin

    2017-05-01

    Intracellular lactoferrin (Lac) and lysozyme (Lys) content play an important role in regulating inflammation and promoting host protection. While exercise has demonstrated an increase in Lac and Lys concentration in exocrine solutions, little is known regarding intracellular concentration changes in response to exercise. To quantify intracellular Lac and Lys concentration before and after exercise in salivary CD45 + CD15 + cells. 11 males (20.3 ± 0.8 years, 57.2 ± 7.6 mL/kg/min V̇O 2pk , 11.1 ± 3.9% body fat) ran for 45 min at 75% of VO 2pk . 12 mL of stimulated saliva were collected pre and immediately post exercise. Saliva was filtered through a 30-µm filter before analysis of leukocytes (CD45 + ) and granulocytes (CD45 + CD15 + ) using flow cytometry. Median fluorescent intensity (MFI) of Lac increased from pre (64,268 ± 46,036 MFI) to post (117,134 ± 88,115 MFI) exercise (p exercise (pre: 16,933 ± 8249; post: 11,616 ± 6875) (p exercise. Conversely, the exercise-associated decrease of intracellular Lys content could be the cause of increased Lys in exocrine solutions.

  12. Red cell ferritin and iron stores in chronic granulocytic leukemia

    International Nuclear Information System (INIS)

    Cermak, J.; Neuwirth, J.; Voglova, J.; Brabec, V.; Chrobak, L.

    1994-01-01

    Basic red cell ferritin was investigated in 28 patients with different phases of chronic granulocytic leukemia (GCL). Red cell ferritin was significantly decreased in remission after busulphan treatment and significantly elevated in the blast crisis as compared to healthy controls. Bone marrow stainable iron was decreased or absent in 86% of patients in the initial phase at the time of diagnosis and in 92% of those in remission. Red cell ferritin correlated with serum ferritin, however, serum ferritin level remained above normal range during all phases of the disease. A negative correlation between red cell ferritin and hemoglobin (Hb) (r = -0.605, p < 0.001) suggested that red cell ferritin level reflected the rate of iron utilization for heme synthesis. Decrease red cell iron observed in the remission may be explained by regression of dyserythropoiesis and by restoration of normal Hb synthesis after busulphan treatment. A progressive dyserythropoiesis in the blast crisis may lead to an increased red cell ferritin level. (author)

  13. Complement activated granulocytes can cause autologous tissue destruction in man

    Directory of Open Access Journals (Sweden)

    E. Löhde

    1992-01-01

    Full Text Available Activation of polymorphonuclear granulocytes (PMNs by C5a is thought to be important in the pathogenesis of multiple organ failure during sepsis and after trauma. In our experiment exposure of human PMNs to autologous zymosan activated plasma (ZAP leads to a rapid increase in chemiluminescence. Heating the ZAP at 56°C for 30 min did not alter the changes, while untreated plasma induced only baseline activity. The respiratory burst could be completely abolished by decomplementation and preincubation with rabbit antihuman C5a antibodies. Observation of human omentum using electron microscopy showed intravascular aggregation of PMNs, with capillary thrombosis and diapedesis of the cells through endothelial junctions 90 s after exposure to ZAP. PMNs caused disruption of connections between the mesothelial cells. After 4 min the mesothelium was completely destroyed, and connective tissue and fat cells exposed. Native plasma and minimum essential medium did not induce any morphological changes. These data support the concept that C5a activated PMNs can cause endothelial and mesothelial damage in man. Even though a causal relationship between anaphylatoxins and organ failure cannot be proved by these experiments C5a seems to be an important mediator in the pathogenesis of changes induced by severe sepsis and trauma in man.

  14. Utility of Immature Granulocyte Percentage in Pediatric Appendicitis

    Science.gov (United States)

    Mathews, Eleanor K.; Griffin, Russell L.; Mortellaro, Vincent; Beierle, Elizabeth A.; Harmon, Carroll M.; Chen, Mike K.; Russell, Robert T.

    2014-01-01

    Background Acute appendicitis is the most common cause of abdominal surgery in children. Adjuncts are utilized to help clinicians predict acute or perforated appendicitis, which may affect treatment decisions. Automated hematologic analyzers can perform more accurate automated differentials including immature granulocyte percentages (IG%). Elevated IG% has demonstrated improved accuracy for predicting sepsis in the neonatal population than traditional immature to total neutrophil count (I/T) ratios. We intended to assess the additional discriminatory ability of IG% to traditionally assessed parameters in the differentiation between acute and perforated appendicitis. Materials and Methods We identified all patients with appendicitis from July 2012 to June 2013 by ICD-9 code. Charts were reviewed for relevant demographic, clinical, and outcome data, which were compared between acute and perforated appendicitis groups using Fischer’s exact and t-test for categorical and continuous variables, respectively. We utilized an adjusted logistic regression model utilizing clinical lab values to predict the odds of perforated appendicitis. Results 251 patients were included in the analysis. Those with perforated appendicitis had a higher white blood cell (WBC) count (p=0.0063), C-reactive protein (CRP) (pappendicitis. The c-statistic of the final model was 0.70, suggesting fair discriminatory ability in predicting perforated appendicitis. Conclusions IG% did not provide any additional benefit to elevated CRP and presence of left shift in the differentiation between acute and perforated appendicitis. PMID:24793450

  15. Solution NMR Structures of Oxidized and Reduced Ehrlichia chaffeensis thioredoxin: NMR-Invisible Structure Owing to Backbone Dynamics

    Energy Technology Data Exchange (ETDEWEB)

    Buchko, Garry W.; Hewitt, Stephen N.; Van Voorhis, Wesley C.; Myler, Peter J.

    2018-01-02

    Thioredoxins (Trxs) are small ubiquitous proteins that participate in a diverse variety of redox reactions via the reversible oxidation of two cysteine thiol groups in a structurally conserved active site, CGPC. Here, we describe the NMR solution structures of a Trx from Ehrlichia chaffeensis (Ec-Trx, ECH_0218), the etiological agent responsible for human monocytic ehrlichiosis, in both the oxidized and reduced states. The overall topology of the calculated structures is similar in both redox states and similar to other Trx structures, a five-strand, mixed -sheet (1:3:2:4:5) surrounded by four -helices. Unlike other Trxs studied by NMR in both redox states, the 1H-15N HSQC spectra of reduced Ec-Trx was missing eight amide cross peaks relative to the spectra of oxidized Ec-Trx. These missing amides correspond to residues C32-E39 in the active site containing helix (2) and S72-I75 in a loop near the active site and suggest a substantial change in the backbone dynamics associated with the formation of an intramolecular C32-C35 disulfide bond.

  16. Paclitaxel, ifosfamide and cisplatin with granulocyte colony-stimulating factor or recombinant human interleukin 3 and granulocyte colony-stimulating factor in ovarian cancer : A feasibility study

    NARCIS (Netherlands)

    Veldhuis, GJ; Willemse, PHB; Beijnen, JH; Piersma, H; vanderGraaf, WTA; deVries, EGE; Boonstra, J.

    1997-01-01

    The tolerability and efficacy of four courses of paclitaxel and ifosfamide plus cisplatin every 3 weeks was evaluated in patients with residual or refractory ovarian cancer. Additionally, supportive haematological effects of recombinant human interleukin 3 (rhIL-3) and recombinant human granulocyte

  17. Increased Granulocyte Heparanase Activity in Neutrophils from Patients with Lupus Nephritis and Idiopathic Membranous Nephropathy.

    Science.gov (United States)

    Szymczak, Maciej; Kuźniar, Jakub; Kopeć, Wacław; Żabińska, Marcelina; Marchewka, Zofia; Kościelska-Kasprzak, Katarzyna; Klinger, Marian

    2017-02-01

    Heparanase is a β-glucuronidase that cleaves sugar chains of heparan sulfate proteoglycans. It is believed that heparanase may be involved in the pathogenesis of proteinuria. The aim of this study was to assess the significance of heparanase in the pathogenesis of particular glomerulonephritis types. The evaluation of heparanase activity in serum, urine, and granulocytes and superoxide dismutase (SOD) activity in granulocytes of patients with lupus nephritis (n = 17), membranous nephropathy (n = 11), IgA nephropathy (n = 12), focal and segmental glomerulosclerosis (n = 18), mesangiocapillary glomerulonephritis (n = 12) and in 19 healthy volunteers were performed. The heparanase activity in granulocytes of patients with lupus nephritis and membranous nephropathy was higher than heparanase activity in granulocytes in the control group (p = 0.02 in both cases). This is the first observation of this phenomenon. There was no difference between SOD activity in granulocytes of patients with all assessed types of glomerulonephritis and the control group. A positive correlation between heparanase activity in urine and double-strain DNA antibodies (r = 0.51; p = 0.04), and reverse correlations between heparanase in urine and hemolytic activity of the complement (r = -0.57; p = 0.03) in the lupus nephritis group, and between heparanase activity in granulocytes and serum total protein level (r = -0.69; p = 0.02) in membranous nephropathy were observed. Increase in heparanase activity without changes in superoxide dismutase activity in the granulocytes from patients with lupus nephritis and membranous nephropathy was observed. It may be used as one of the markers of these disease activities.

  18. Tumour-derived GM-CSF promotes granulocyte immunosuppression in mesothelioma patients.

    Science.gov (United States)

    Khanna, Swati; Graef, Suzanne; Mussai, Francis; Thomas, Anish; Wali, Neha; Yenidunya, Bahar Guliz; Yuan, Constance M; Morrow, Betsy; Zhang, Jingli; Korangy, Firouzeh; Greten, Tim F; Steinberg, Seth M; Stetler-Stevenson, Maryalice; Middleton, Gary; De Santo, Carmela; Hassan, Raffit

    2018-03-30

    The cross talk between tumour cells, myeloid cells, and T cells play a critical role in tumour pathogenesis and response to immunotherapies. Although the aetiology of mesothelioma is well understood the impact of mesothelioma on the surrounding immune microenvironment is less well studied. In this study the effect of the mesothelioma microenvironment on circulating and infiltrating granulocytes and T cells is investigated. Tumour and peripheral blood from mesothelioma patients were evaluated for presence of granulocytes, which were then tested for their T cell suppression. Co-cultures of granulocytes, mesothelioma cells, T cells were used to identify the mechanism of T cell inhibition. Analysis of tumours showed that the mesothelioma microenvironment is enriched in infiltrating granulocytes, which inhibit T cell proliferation and activation. Characterisation of the blood at diagnosis identified similar, circulating, immunosuppressive CD11b+CD15+HLADR- granulocytes at increased frequency compared to healthy controls. Culture of healthy-donor granulocytes with human mesothelioma cells showed that GM-CSF upregulates NOX2 expression and the release of Reactive Oxygen Species (ROS) from granulocytes, resulting in T cell suppression. Immunohistochemistry and transcriptomic analysis revealed that a majority of mesothelioma tumours express GM-CSF and that higher GM-CSF expression correlated with clinical progression. Blockade of GM-CSF with neutralising antibody, or ROS inhibition, restored T cell proliferation suggesting that targeting of GM-CSF could be of therapeutic benefit in these patients. Our study presents the mechanism behind the cross-talk between mesothelioma and the immune micro-environment and indicates that targeting GM-CSF could be a novel treatment strategy to augment immunotherapy. Copyright ©2018, American Association for Cancer Research.

  19. Observations on transition of polycythaemia vera into acute or chronic granulocytic leukaemia during treatment with radioactive phosphorus 32P

    International Nuclear Information System (INIS)

    Krasnik, W.

    1975-01-01

    In a group of 172 cases of polycythaemia vera treated with radioactive phosphorus 32 P acute granulocytic leukaemia developed in 3 cases and chronic granulocytic leukaemia in 6 cases. Development of acute granulocytic leukaemia during treatment with radioactive phosphorus for polycythaemia vera may be considered with some probability as a result of leukaemia-inducing action of ionizing radiation. Transition of polycythaemia vera into chronic granulocytic leukaemia seems to a natural outcome of this complex myeloproliferative syndrome in patients with survival prolonged by treatment with 32 P. (author)

  20. A Novel Tool for High-Throughput Screening of Granulocyte-Specific Antibodies Using the Automated Flow Cytometric Granulocyte Immunofluorescence Test (Flow-GIFT

    Directory of Open Access Journals (Sweden)

    Xuan Duc Nguyen

    2011-01-01

    Full Text Available Transfusion-related acute lung injury (TRALI is a severe complication related with blood transfusion. TRALI has usually been associated with antibodies against leukocytes. The flow cytometric granulocyte immunofluorescence test (Flow-GIFT has been introduced for routine use when investigating patients and healthy blood donors. Here we describe a novel tool in the automation of the Flow-GIFT that enables a rapid screening of blood donations. We analyzed 440 sera from healthy female blood donors for the presence of granulocyte antibodies. As positive controls, 12 sera with known antibodies against anti-HNA-1a, -b, -2a; and -3a were additionally investigated. Whole-blood samples from HNA-typed donors were collected and the test cells isolated using cell sedimentation in a Ficoll density gradient. Subsequently, leukocytes were incubated with the respective serum and binding of antibodies was detected using FITC-conjugated antihuman antibody. 7-AAD was used to exclude dead cells. Pipetting steps were automated using the Biomek NXp Multichannel Automation Workstation. All samples were prepared in the 96-deep well plates and analyzed by flow cytometry. The standard granulocyte immunofluorescence test (GIFT and granulocyte agglutination test (GAT were also performed as reference methods. Sixteen sera were positive in the automated Flow-GIFT, while five of these sera were negative in the standard GIFT (anti—HNA 3a, n = 3; anti—HNA-1b, n = 1 and GAT (anti—HNA-2a, n = 1. The automated Flow-GIFT was able to detect all granulocyte antibodies, which could be only detected in GIFT in combination with GAT. In serial dilution tests, the automated Flow-GIFT detected the antibodies at higher dilutions than the reference methods GIFT and GAT. The Flow-GIFT proved to be feasible for automation. This novel high-throughput system allows an effective antigranulocyte antibody detection in a large donor population in order to prevent TRALI due to transfusion of

  1. A novel tool for high-throughput screening of granulocyte-specific antibodies using the automated flow cytometric granulocyte immunofluorescence test (Flow-GIFT).

    Science.gov (United States)

    Nguyen, Xuan Duc; Dengler, Thomas; Schulz-Linkholt, Monika; Klüter, Harald

    2011-02-03

    Transfusion-related acute lung injury (TRALI) is a severe complication related with blood transfusion. TRALI has usually been associated with antibodies against leukocytes. The flow cytometric granulocyte immunofluorescence test (Flow-GIFT) has been introduced for routine use when investigating patients and healthy blood donors. Here we describe a novel tool in the automation of the Flow-GIFT that enables a rapid screening of blood donations. We analyzed 440 sera from healthy female blood donors for the presence of granulocyte antibodies. As positive controls, 12 sera with known antibodies against anti-HNA-1a, -b, -2a; and -3a were additionally investigated. Whole-blood samples from HNA-typed donors were collected and the test cells isolated using cell sedimentation in a Ficoll density gradient. Subsequently, leukocytes were incubated with the respective serum and binding of antibodies was detected using FITC-conjugated antihuman antibody. 7-AAD was used to exclude dead cells. Pipetting steps were automated using the Biomek NXp Multichannel Automation Workstation. All samples were prepared in the 96-deep well plates and analyzed by flow cytometry. The standard granulocyte immunofluorescence test (GIFT) and granulocyte agglutination test (GAT) were also performed as reference methods. Sixteen sera were positive in the automated Flow-GIFT, while five of these sera were negative in the standard GIFT (anti-HNA 3a, n = 3; anti-HNA-1b, n = 1) and GAT (anti-HNA-2a, n = 1). The automated Flow-GIFT was able to detect all granulocyte antibodies, which could be only detected in GIFT in combination with GAT. In serial dilution tests, the automated Flow-GIFT detected the antibodies at higher dilutions than the reference methods GIFT and GAT. The Flow-GIFT proved to be feasible for automation. This novel high-throughput system allows an effective antigranulocyte antibody detection in a large donor population in order to prevent TRALI due to transfusion of blood products.

  2. Granulocyte colony-stimulating factor mobilizes dormant hematopoietic stem cells without proliferation in mice.

    Science.gov (United States)

    Bernitz, Jeffrey M; Daniel, Michael G; Fstkchyan, Yesai S; Moore, Kateri

    2017-04-06

    Granulocyte colony-stimulating factor (G-CSF) is used clinically to treat leukopenia and to enforce hematopoietic stem cell (HSC) mobilization to the peripheral blood (PB). However, G-CSF is also produced in response to infection, and excessive exposure reduces HSC repopulation capacity. Previous work has shown that dormant HSCs contain all the long-term repopulation potential in the bone marrow (BM), and that as HSCs accumulate a divisional history, they progressively lose regenerative potential. As G-CSF treatment also induces HSC proliferation, we sought to examine whether G-CSF-mediated repopulation defects are a result of increased proliferative history. To do so, we used an established H2BGFP label retaining system to track HSC divisions in response to G-CSF. Our results show that dormant HSCs are preferentially mobilized to the PB on G-CSF treatment. We find that this mobilization does not result in H2BGFP label dilution of dormant HSCs, suggesting that G-CSF does not stimulate dormant HSC proliferation. Instead, we find that proliferation within the HSC compartment is restricted to CD41-expressing cells that function with short-term, and primarily myeloid, regenerative potential. Finally, we show CD41 expression is up-regulated within the BM HSC compartment in response to G-CSF treatment. This emergent CD41 Hi HSC fraction demonstrates no observable engraftment potential, but directly matures into megakaryocytes when placed in culture. Together, our results demonstrate that dormant HSCs mobilize in response to G-CSF treatment without dividing, and that G-CSF-mediated proliferation is restricted to cells with limited regenerative potential found within the HSC compartment. © 2017 by The American Society of Hematology.

  3. Detection of Ehrlichia spp., Anaplasma spp., Rickettsia spp., and Other Eubacteria in Ticks from the Thai-Myanmar Border and Vietnam

    OpenAIRE

    Parola, Philippe; Cornet, Jean-Paul; Sanogo, Yibayiri Osée; Miller, R. Scott; Thien, Huynh Van; Gonzalez, Jean-Paul; Raoult, Didier; Telford III, Sam R.; Wongsrichanalai, Chansuda

    2003-01-01

    A total of 650 ticks, including 13 species from five genera, were collected from animals, from people, or by flagging of the vegetation at sites on the Thai-Myanmar border and in Vietnam. They were tested by PCR to detect DNA of bacteria of the order Rickettsiales. Three Anaplasma spp. were detected in ticks collected in Thailand, including (i) Anaplasma sp. strain AnDa465, which was considered a genotype of Anaplasma platys (formerly Ehrlichia platys) and which was obtained from Dermacentor ...

  4. Diagnosis, Treatment, and Prevention of Lyme Disease, Human Granulocytic Anaplasmosis, and Babesiosis: A Review.

    Science.gov (United States)

    Sanchez, Edgar; Vannier, Edouard; Wormser, Gary P; Hu, Linden T

    2016-04-26

    Lyme disease, human granulocytic anaplasmosis (HGA), and babesiosis are emerging tick-borne infections. To provide an update on diagnosis, treatment, and prevention of tick-borne infections. Search of PubMed and Scopus for articles on diagnosis, treatment, and prevention of tick-borne infections published in English from January 2005 through December 2015. The search yielded 3550 articles for diagnosis and treatment and 752 articles for prevention. Of these articles, 361 were reviewed in depth. Evidence supports the use of US Food and Drug Administration-approved serologic tests, such as an enzyme immunoassay (EIA), followed by Western blot testing, to diagnose extracutaneous manifestations of Lyme disease. Microscopy and polymerase chain reaction assay of blood specimens are used to diagnose active HGA and babesiosis. The efficacy of oral doxycycline, amoxicillin, and cefuroxime axetil for treating Lyme disease has been established in multiple trials. Ceftriaxone is recommended when parenteral antibiotic therapy is recommended. Multiple trials have shown efficacy for a 10-day course of oral doxycycline for treatment of erythema migrans and for a 14-day course for treatment of early neurologic Lyme disease in ambulatory patients. Evidence indicates that a 10-day course of oral doxycycline is effective for HGA and that a 7- to 10-day course of azithromycin plus atovaquone is effective for mild babesiosis. Based on multiple case reports, a 7- to 10-day course of clindamycin plus quinine is often used to treat severe babesiosis. A recent study supports a minimum of 6 weeks of antibiotics for highly immunocompromised patients with babesiosis, with no parasites detected on blood smear for at least the final 2 weeks of treatment. Evidence is evolving regarding the diagnosis, treatment, and prevention of Lyme disease, HGA, and babesiosis. Recent evidence supports treating patients with erythema migrans for no longer than 10 days when doxycycline is used and prescription

  5. Lung transit of /sup 111/Indium-labelled granulocytes. Relationship to labelling techniques

    Energy Technology Data Exchange (ETDEWEB)

    Saverymuttu, S.H.; Peters, A.M.; Danpure, H.J.; Reavy, H.J.; Osman, S.; Lavender, J.P. (Hammersmith Hospital, London, England)

    1983-01-01

    The early in vivo distribution of /sup 111/Indium-labelled granulocytes, recorded by dynamic imaging using a gamma camera and computer, varied according to the separation and labelling technique. Following i.v. bolus injection, 4 kinetic patterns could be identified: (A) rapid transit through the pulmonary vasculature, (B) delayed transit through the lung with clearance by about 30 min, (C) complete retention by the lung, for up to 10 min, followed by slow release over a period of 1 to 2 h, (D) delayed transit through the lung with a similar time course to (B) but with subsequent heavy liver uptake. Granulocytes labelled with /sup 111/In-tropolonate and maintained in plasma throughout the labelling procedure, whether injected as a 'pure' (separated by plasma-enriched density gradient centrifugation) or 'crude' (seprated by differential centrifugation) preparation, displayed type A kinetics, thought to most closely represent the normal behaviour of granulocytes. 'Crude' cells labelled in saline with /sup 111/In-acetylacetonate displayed type B kinetics. 'Pure' cells isolated on Percoll-saline and labelled in saline with /sup 111/In-acetylacetonate displayed type C kinetics, thought to represent granulocyte 'stimulation' and/or damage, or type D kientics, thought to represent severe damage. The importance is stressed of labelling granulocytes for kinetic studies with a technique that results in minimal alteration of cell behaviour.

  6. Effects of irradiation and storage on granulocytes harvested by continuous-flow centrifugation

    International Nuclear Information System (INIS)

    Patrone, F.; Dallegri, F.; Brema, F.; Sacchetti, C.

    1979-01-01

    Five normal subjects were subjected to leukapheresis by continuous-flow-centrifugation (CFC) in the Aminco Celltrifuge. Granulocyte functional capacities were evaluated on the venous blood samples drawn before apheresis and on the cellrich plasma collected by CFC, immediately after collection and after short-term storage at 4degC with or without previous irradiation (1500 rad, 50 rad/min). The CFC technique has been shown to provide cells without functional damage. Irradiation did not appear to influence granulocyte function, as evaluated by in vitro studies. The data demonstrate that granulocytes maintain, even after irradiation, functional activities similar to those found immediately after collection for up to 24 hours of storage at 4degC and exhibit only a moderate loss of function after 48 h. Chemotaxis appears to be the most sensitive detector of cellular damage of stored granulocytes, either irradiated or non-irradiated; this technique may be the most useful for assessment of granulocyte function before transfusion. (author)

  7. Aliphatic alcohol contaminants of illegally produced spirits inhibit phagocytosis by human granulocytes.

    Science.gov (United States)

    Pál, László; Árnyas, Ervin M; Tóth, Béla; Ádám, Balázs; Rácz, Gábor; Ádány, Róza; McKee, Martin; Szűcs, Sándor

    2013-04-01

    Unregulated production of spirits in many countries leads to products containing appreciable levels of aliphatic alcohols (AAs) and is the main source of human exposure to these substances worldwide. Previous studies have confirmed that alcohol abuse can lead to ethanol-induced immunosuppression and thereby increased susceptibility to infectious diseases. Granulocytes, as professional phagocytic cells, play a crucial role in engulfment and killing of pathogenic microorganisms. Thus, a decrease in their phagocytic activity has been invoked as a factor in the impaired antimicrobial defense observed in alcoholics. However, AAs consumed as contaminants of illicit spirits may also influence phagocytosis, thereby contributing to a further decrease in microbicidal activity but, so far, this has not been studied. Therefore, the aim of this study was to measure granulocyte phagocytosis following treatment of granulocytes with those higher alcohols found in illegal spirits. Granulocytes were isolated from human peripheral blood. Then phagocytosis of opsonized zymosan particles by granulocytes treated with AAs individually and in combination was determined. These alcohols inhibited phagocytosis in a concentration-dependent manner and at lower concentrations when combined than when tested individually. Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit phagocytosis in a clinically meaningful way in episodic heavy drinkers.

  8. Diagnostic value of (111)In-granulocyte scintigraphy in patients with fever of unknown origin

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Lebech, Anne-Mette

    2002-01-01

    111In-granulocyte scintigraphy is often used as a diagnostic tool in patients with fever of unknown origin (FUO). However, its diagnostic performance has been studied in only a limited number of investigations, with most having been published more than 10 y ago; in addition, a broad range...... of sensitivities and specificities has been reported. Therefore, the aim of this study was to investigate the diagnostic value of granulocyte scintigraphy in patients fulfilling the criteria of FUO. Also studied was whether increased peripheral leukocyte count or C-reactive protein (CRP) level could be used...... to select patients for scintigraphy to raise the diagnostic value. METHODS: For 31 patients with true FUO who underwent granulocyte scintigraphy at a third-line referral hospital between 1995 and 2000, the files and scintigraphy findings were reviewed retrospectively to test the ability of scintigraphy...

  9. Flow cytometry evidence of human granulocytes interaction with polyhedral oligomeric silsesquioxanes: effect of nanoparticle charge

    International Nuclear Information System (INIS)

    Renò, Filippo; Rizzi, Manuela; Pittarella, Pamela; Carniato, Fabio; Olivero, Francesco; Marchese, Leonardo

    2013-01-01

    Nanoparticles (NPs) entering the human body are immediately confronted with the innate part of human immune system. In particular, monocyte and neutrophil granulocytes readily clear particles by phagocytosis, even if in the case of NPs the uptake mechanism may be classified as macropinocytosis. Among engineered nanoparticles, in the last years, siliceous materials have emerged as promising materials for several applications ranging from catalysis to biomedical. The polyhedral oligomeric silsesquioxanes (POSS) are nanodimensional, easily synthesizable molecular compounds and POSS-based systems are promising carriers for biological molecules. In this work, the ability of human granulocytes to uptake positively and negatively charged POSS was measured using a simple flow cytometry analysis based on cell size modifications. The data obtained showed that after a 30 min exposure only positive NPs were uptaken by human granulocyte using both macropinocytosis and clathrin-mediated mechanisms as demonstrated by uptake inhibition mediated by amiloride and chlorpromazine. (paper)

  10. CD18 expression in granulocytes infiltrating the vitreous fluid in patients with diabetic retinopathy

    Institute of Scientific and Technical Information of China (English)

    Qi; Zhu; Hu-Ping; Song

    2015-01-01

    AIM: To assess the levels of CD18 on the surface of granulocytes infiltrating the vitreous fluid in patients with diabetic retinopathy(DR).METHODS: Vitreous samples from twelve patients with non-proliferative DR with significant macula edema(group A), 33 patients with proliferative DR(grade 3 as group B, n =14, and, grade 4 as group C, n =19) were obtained during pars plana vitrectomy. Vitreous samples from 12 patients with macular hole as controls(group D)were analyzed together. The infiltrating of granulocytes and its surface level of CD18 were measured by flow cytometry. The level of CD18 was presented as the mean channel fluorescence(MCF) on a logarithmic scale. RESULTS: Granulocytes were detected in 6 of 12 vitreous samples from group A, 9 of 14 from group B, 15 of 19 from group C, and none of 12 from group D. MCF of CD18 on granulocytes from groups A, B, and C were2.978 ±1.446, 3.201 ±0.692, and 4.072 ±0.837, respectively.The difference was significant(F =4.354, P =0.021).Subjects with more severe DR were more likely to have a higher level of CD18 MCF(trend test, 掊2=7.351, P =0.007).CD18 MCF was significantly associated with the development of DR(r =0.46, P =0.005 and β =0.147, P =0.035).CONCLUSION: Our results confirm the presence of granulocytes and the elevated levels of CD18 on the surface of them in the vitreous fluid from DR patients.These results may provide indirect evidence shown that granulocytes activation also has occurred in the retinal local compared to non-DR control.

  11. Membrane permeability of the human granulocyte to water, dimethyl sulfoxide, glycerol, propylene glycol and ethylene glycol.

    Science.gov (United States)

    Vian, Alex M; Higgins, Adam Z

    2014-02-01

    Granulocytes are currently transfused as soon as possible after collection because they rapidly deteriorate after being removed from the body. This short shelf life complicates the logistics of granulocyte collection, banking, and safety testing. Cryopreservation has the potential to significantly increase shelf life; however, cryopreservation of granulocytes has proven to be difficult. In this study, we investigate the membrane permeability properties of human granulocytes, with the ultimate goal of using membrane transport modeling to facilitate development of improved cryopreservation methods. We first measured the equilibrium volume of human granulocytes in a range of hypo- and hypertonic solutions and fit the resulting data using a Boyle-van't Hoff model. This yielded an isotonic cell volume of 378 μm(3) and an osmotically inactive volume of 165 μm(3). To determine the permeability of the granulocyte membrane to water and cryoprotectant (CPA), cells were injected into well-mixed CPA solution while collecting volume measurements using a Coulter Counter. These experiments were performed at temperatures ranging from 4 to 37°C for exposure to dimethyl sulfoxide, glycerol, ethylene glycol, and propylene glycol. The best-fit water permeability was similar in the presence of all of the CPAs, with an average value at 21°C of 0.18 μmatm(-1)min(-1). The activation energy for water transport ranged from 41 to 61 kJ/mol. The CPA permeability at 21°C was 6.4, 1.0, 8.4, and 4.0 μm/min for dimethyl sulfoxide, glycerol, ethylene glycol, and propylene glycol, respectively, and the activation energy for CPA transport ranged between 59 and 68 kJ/mol. Copyright © 2013 Elsevier Inc. All rights reserved.

  12. /sup 99/Tcsup(m)-HMPAO labelled leucocytes: comparison with /sup 111/In-tropolonate labelled granulocytes

    Energy Technology Data Exchange (ETDEWEB)

    Peters, A.M.; Roddie, M.E.; Zacharopoulos, G.P.; George, P.; Stuttle, A.W.J.; Lavender, J.P.; Danpure, H.J.; Osman, S.

    1988-06-01

    The lipophilic complex, /sup 99/Tcsup(m)-hexamethylpropyleneamine oxime (HMPAO) is an efficient leucocyte label, and labels granulocytes with more stability than mononuclear leucocytes. The recovery of /sup 99/Tcsup(m)-HMPAO granulocytes was similar to /sup 111/In-labelled granulocytes isolated and labelled in plasma using tropolone. The Tsub(1/2) of /sup 99/Tcsup(m)-HMPAO labelled granulocytes in blood was less than that of /sup 111/In-labelled granulocytes. The initial biodistribution of /sup 99/Tcsup(m)-labelled leucocytes was similar to /sup 111/In-labelled granulocytes, with a rapid initial lung transit, prominent splenic activity, bone marrow activity and minimal hepatic activity, although, unlike /sup 111/In, /sup 99/Tcsup(m) activity was also seen in urine, occasionally in the gallbladder, and, from about 4 h, consistently in the colon. Bone marrow activity was particularly prominent with /sup 99/Tcsup(m). About 6% of /sup 99/Tcsup(m) was excreted in the faeces up to 48 h after injection, and about 17% in urine up to 24 h. The time-activity curves of reticuloendothelial activity up to 24 h were broadly similar for the two labelled cell preparations. Clinical information given by the two agents was similar in 27 of 30 patients who received both. We conclude that with respect to granulocyte kinetics and clinical data, /sup 99/Tcsup(m)-HMPAO labelled leucocytes are comparable with /sup 111/In-tropolonate labelled granulocytes.

  13. Granulocytic sarcoma presenting with necrotic cervical lymph nodes as an initial manifestation of childhood leukaemia: imaging features

    Energy Technology Data Exchange (ETDEWEB)

    An, Sang Bu; Cheon, Jung-Eun; Kim, In-One; Kim, Woo Sun [Seoul National University College of Medicine, Department of Radiology, Seoul (Korea); Seoul National University Medical Research Center, Institute of Radiation Medicine, Seoul (Korea); Ahn, Hyo Seop; Shin, Hee Young; Kang, Hyoung Jin; Yeon, Kyung Mo [Seoul National University College of Medicine, Department of Pediatrics, Cancer Research Institute, Seoul (Korea)

    2008-06-15

    We present two cases of granulocytic sarcoma of the cervical lymph nodes with central necrosis as an initial manifestation of childhood leukaemia, focusing on the imaging features. Recognition of the CT and MR imaging findings of granulocytic sarcoma involving the cervical lymph nodes assists the differential diagnosis of noninfective lymphadenopathy in children. (orig.)

  14. Selective binding and oligomerization of the murine granulocyte colony-stimulating factor receptor by a low molecular weight, nonpeptidyl ligand.

    Science.gov (United States)

    Doyle, Michael L; Tian, Shin-Shay; Miller, Stephen G; Kessler, Linda; Baker, Audrey E; Brigham-Burke, Michael R; Dillon, Susan B; Duffy, Kevin J; Keenan, Richard M; Lehr, Ruth; Rosen, Jon; Schneeweis, Lumelle A; Trill, John; Young, Peter R; Luengo, Juan I; Lamb, Peter

    2003-03-14

    Granulocyte colony-stimulating factor regulates neutrophil production by binding to a specific receptor, the granulocyte colony-stimulating factor receptor, expressed on cells of the granulocytic lineage. Recombinant forms of granulocyte colony-stimulating factor are used clinically to treat neutropenias. As part of an effort to develop granulocyte colony-stimulating factor mimics with the potential for oral bioavailability, we previously identified a nonpeptidyl small molecule (SB-247464) that selectively activates murine granulocyte colony-stimulating factor signal transduction pathways and promotes neutrophil formation in vivo. To elucidate the mechanism of action of SB-247464, a series of cell-based and biochemical assays were performed. The activity of SB-247464 is strictly dependent on the presence of zinc ions. Titration microcalorimetry experiments using a soluble murine granulocyte colony-stimulating factor receptor construct show that SB-247464 binds to the extracellular domain of the receptor in a zinc ion-dependent manner. Analytical ultracentrifugation studies demonstrate that SB-247464 induces self-association of the N-terminal three-domain fragment in a manner that is consistent with dimerization. SB-247464 induces internalization of granulocyte colony-stimulating factor receptor on intact cells, consistent with a mechanism involving receptor oligomerization. These data show that small nonpeptidyl compounds are capable of selectively binding and inducing productive oligomerization of cytokine receptors.

  15. Diagnostic value of (111)In-granulocyte scintigraphy in patients with fever of unknown origin

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Lebech, Anne-Mette

    2002-01-01

    111In-granulocyte scintigraphy is often used as a diagnostic tool in patients with fever of unknown origin (FUO). However, its diagnostic performance has been studied in only a limited number of investigations, with most having been published more than 10 y ago; in addition, a broad range...... and specificity in cases of FUO, when one takes into account that (111)In-granulocyte scintigraphy is not a first-line test. The high predictive value of a scintigram showing negative findings may be especially valuable for ruling out an infectious cause of FUO. Neither peripheral leukocyte count nor CRP levels...

  16. The Granulocyte-colony stimulating factor has a dual role in neuronal and vascular plasticity

    Directory of Open Access Journals (Sweden)

    Stephanie eWallner

    2015-08-01

    Full Text Available Granulocyte-colony stimulating factor (G-CSF is a growth factor that has originally been identified several decades ago as a hematopoietic factor required mainly for the generation of neutrophilic granulocytes, and is in clinical use for that. More recently, it has been discovered that G-CSF also plays a role in the brain as a growth factor for neurons and neural stem cells, and as a factor involved in the plasticity of the vasculature. We review and discuss these dual properties in view of the neuroregenerative potential of this growth factor.

  17. [Reversibility of the leukocyte activation state studied in a model of endogenous pyrogen formation by granulocytes].

    Science.gov (United States)

    Rybakina, E G; Sorokin, A V

    1980-08-01

    The pyrogen-releasing capacity of rabbit exudate granulocytes can be temporarily suppressed during incubation in the whole plasma and then recovered during cell transfer into 0.15 M NaCl or stimulation with the bacterial lipopolysaccharide, pyrogenal. The inhibitors of protein synthesis added to the granulocytes when they are being transferred from plasma to 0.15 M NaCl do not suppress the pyrogen release. The inhibitory action of the whole plasma on the pyrogen release is due to the presence in it of potassium and calcium ions. The inhibitory factors of plasma reversibly suppress the pyrogen release but do not eliminate the leukocyte activation.

  18. A preliminary parasitological survey of hepatozoon spp. Infection in dogs in mashhad, iran.

    Science.gov (United States)

    Amoli, Aa Rahmani; Khoshnegah, J; Razmi, Ghr

    2012-01-01

    We attempted to determine the prevalence of Hepatozoon spp. infection in Mashhad, northeast of Iran, via blood smear parasitology. The prevalence was investigated by examination of blood smear parasitology, using blood samples collected from 254 dogs (51 strays and 203 privately owned-dogs). Two stray dogs (2/51; 3.92%) and two privately-owned dogs (2/203; 0.98%) were infected with Hepatozoon spp. Therefore, as per blood smear parasitology, the prevalence of Hepatozoon spp. infection was 1.57% (4/254). Sixteen out of 254 dogs (6.29%) were infested with ticks; all of which were Rhipicephalus sanguineus. One of the dogs infected with Hepatozoon spp. exhibited ticks at the time of examination. Concurrent infection with Ehrlichia canis and Leishmania infantum was not detected in the four Hepatozoon spp. infected dogs. This is the first epidemiological study on the prevalence of Hepatozoon spp. infection in dogs in Iran.

  19. Prevalence of Dirofilaria immitis, Ehrlichia canis, Borrelia burgdorferi sensu lato, Anaplasma spp. and Leishmania infantum in apparently healthy and CVBD-suspect dogs in Portugal - a national serological study

    Directory of Open Access Journals (Sweden)

    Cardoso Luís

    2012-03-01

    Full Text Available Abstract Background Canine vector-borne diseases (CVBDs are caused by a wide range of pathogens transmitted to dogs by arthropods including ticks and insects. Many CVBD-agents are of zoonotic concern, with dogs potentially serving as reservoirs and sentinels for human infections. The present study aimed at assessing the seroprevalence of infection with or exposure to Dirofilaria immitis, Ehrlichia canis, Borrelia burgdorferi sensu lato, Anaplasma spp. and Leishmania infantum in dogs in Portugal. Methods Based on 120 veterinary medical centres from all the regions of mainland and insular Portugal, 557 apparently healthy and 628 CVBD-suspect dogs were sampled. Serum, plasma or whole blood was tested for qualitative detection of D. immitis antigen and antibodies to E. canis, B. burgdorferi s. l., Anaplasma spp. and L. infantum with two commercial in-clinic enzyme-linked immunosorbent assay kits. Odds ratios (OR were calculated by logistic regression analysis to identify independent risk factors of exposure to the vector-borne agents. Results Total positivity levels to D. immitis, E. canis, B. burgdorferi, Anaplasma spp., L. infantum, one or more agents and mixed agents were 3.6%, 4.1%, 0.2%, 4.5%, 4.3%, 14.0% and 2.0% in the healthy group, and 8.9%, 16.4%, 0.5%, 9.2%, 25.2%, 46.3% and 11.6% in the clinically suspect group, respectively. Non-use of ectoparasiticides was a risk factor for positivity to one or more agents both in the apparently healthy (OR = 2.1 and CVBD-suspect (OR = 1.5 dogs. Seropositivity to L. infantum (OR = 7.6, E. canis (OR = 4.1 and D. immitis (OR = 2.4 were identified as risk factors for the presence of clinical signs compatible with CVBDs. Positivity to mixed agents was not found to be a risk factor for disease. Conclusions Dogs in Portugal are at risk of becoming infected with vector-borne pathogens, some of which are of zoonotic concern. CVBDs should be considered by practitioners and prophylactic measures must be put in

  20. Seroprevalence of canine dirofilariosis, granulocytic anaplasmosis and lyme borreliosis of public health importance in dogs from India’s North East

    Directory of Open Access Journals (Sweden)

    S. K. Borthakur

    2014-09-01

    Full Text Available Aim: Vector-borne infections namely dirofilariosis, ehrlichiosis, anaplasmosis and lyme borreliosis are being recognized as emerging and/or re-emerging problems in dogs and man due to rapid extension of zoogeographical ranges of many causative agents through international tourism and increase mobility of dogs at national and international level towards meeting the demand for companion animals in the present day society. Anticipating such situation, a serological study was conducted in dogs from North East India to estimate the prevalence of zoonotically important Dirofilaria immitis, Anaplasma phagocytophilum and Borrelia burgdorferi along with Ehrlichia canis. Materials and Methods: Serological study was carried out using enzyme immunoassay in commercial SNAP 4DX® test kit (Idexx Laboratories, USA. The study was conducted in 191 dogs comprising 82 pets, 57 stray and 52 working dogs owned by defence organizations. Results: The study revealed seroprevalence of mosquito-borne D. immitis (17.80%, tick-borne E. canis (22.51% and A. phagocytophilum (4.71% with an overall 41.88% prevalence of pathogens in single or co-infection. Serological evidence of tick-borne lyme borreliosis due to B. burgdorferi could not be established in dogs in the present study. Of the zoonotic species, highest prevalence of D. immitis was found in the stray dogs (22.80% and that of A. phagocytophilum in pet dogs (6.09%. Conclusion: The results of the present serological study serve as baseline information on the prevalence of A. phagocytophilum in dogs reported for the first time in India and reaffirmation on the high prevalence of D. immitis and E. canis in the North East India.

  1. Ovarian granulocytic sarcoma: a case report and magnetic resonance imaging findings

    International Nuclear Information System (INIS)

    Pereira, Licia Pacheco; Monte, Hipolito

    2008-01-01

    Granulocytic sarcoma (chloroma) is a tumor consisting of myeloid precursors in an extramedullary site. It is complication of both acute and chronic myelogenous leukemias. Although the lesion can occur at any site, ovarian involvement is rare. We report a case of ovary tumor associated with acute myeloid leukaemia and its imaging appearance on magnetic resonance. (author)

  2. Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

    Czech Academy of Sciences Publication Activity Database

    Hofer, Michal; Pospíšil, Milan; Komůrková, Denisa; Hoferová, Zuzana

    2014-01-01

    Roč. 19, č. 4 (2014), s. 4770-4778 ISSN 1420-3049 R&D Projects: GA ČR(CZ) GAP303/11/0128 Institutional support: RVO:68081707 Keywords : granulocyte colony-stimulating factor * radiation accident s * acute radiation syndrome Subject RIV: BO - Biophysics Impact factor: 2.416, year: 2014

  3. Carp macrophages and neutrophilic granulocytes secrete an interleukin-1-like factor.

    NARCIS (Netherlands)

    Verburg-van Kemenade, B.M.L.; Weyts, F.A.A.; Debets, R.; Flik, G.

    1995-01-01

    Carp, Cyprinus carpio L, macrophages and neutrophilic granulocytes obtained from pronephros were cultured. Supernatant was harvested after 48 h and tested for interleukin-1 (IL-1) bioactivity. A concentration-dependent stimulation of proliferation was found of carp Ig− lymphocytes as well as of the

  4. Effect of inflammatory serum of 14C-glucosamine incorporation into bone marrow granulocytes in vitro

    International Nuclear Information System (INIS)

    Evans, W.H.; Wilson, S.M.; Torres, A.R.; Peterson, E.A.; Mage, M.G.

    1979-01-01

    As a preliminary approach to developing a biochemical assay for detecting humoral regulators of granulocyte maturation in the normal and inglammatory states, studies were carried out on the effects of normal inflammatory sera on the incorporation of 14 C-glucosamine into the glycoproteins of bone marrow granulocytes in vitro. We observed that, relative to normal serum, inflammatory serum had a marked stimulatory effect on 14 C-glucosamine incorporation into these glycoproteins. This property of inflammatory serum reached a maximum at about 8 h after the initiation of inflammation in vivo and preceded the maximum increase in the mitotic activity of granulocyte precursors in the marrow by 18 h. It was also found that normal serum contains both dialyzable and heat-sensitive nondialyzable factors that inhibit 14 C-glucosamine incorporation into bone marrow granulocytes in vitro. Data are presented which indicate that the stimulatory effect of inflammatory serum is most likely due to a nondialyzable factor which is capable of blocking the effect of the inhibitors present in normal serum. (author)

  5. Brucella Infection in HIV Infected Patients

    Directory of Open Access Journals (Sweden)

    SeyedAhmad SeyedAlinaghi

    2011-12-01

    Full Text Available The purpose of this study was to assess the possible correlation between Brucella and HIV infections. Iran is a country where HIV infection is expanding and Brucellosis is prevalent. In the present study, 184 HIV infected patients were assigned and for all of them HIV infection was confirmed by western blot test. In order to identify the prevalence rate of Brucella infection and systemic brucellosis in these subjects, sera samples were obtained and Brucella specific serological tests were performed to reveal antibody titers. Detailed history was taken and physical examination was carried out for all of patients. 11 (6% subjects had high titers but only 3 of them were symptomatic. Most of these subjects were injection drug user (IDU men and one was a rural woman. Considering both prevalence rates of Brucella infection (3% and symptomatic brucellosis (0.1% in Iran, our HIV positive patients show higher rates of Brucella infection and systemic brucellosis. Preserved cellular immunity of participants and retention of granulocytes activity may explain this poor association; whereas other explanations such as immunological state difference and non-overlapping geographical distribution of the 2 pathogens have been mentioned by various authors.

  6. The Potential Role of Recombinant Hematopoietic Colony-Stimulating Factors in Preventing Infections in the Immunocompromised Host

    Directory of Open Access Journals (Sweden)

    James Rusthoven

    1991-01-01

    Full Text Available Hematopoietic colony-stimulating factors coordinate the proliferation and maturation of bone marrow and peripheral blood cells during normal hematopoiesis. Most of these factors are now available as recombinant human colony-stimulating factors, and preclinical and clinical testing is proceeding rapidly. Granulocyte and granulocyte/macrophage colony-stimulating factors have been the most extensively studied to date. In human clinical trials, granulocyte colony-stimulating factor improves neutrophil counts and function, reduces episodes of febrile neutropenia, improves neutrophil recovery after disease- or treatment-induced myelosuppression, and reduces the number of serious infections in several neutropenic disease states. Granulocyte/macrophage colony-stimulating factor has similar biological properties but may also improve eosinophil proliferation and function, and platelet cell recovery after myelotoxic bone marrow injury, Interleukin-1 boosts the effects of granulocyte colony-stimulating factor and granulocyte/macrophage colony-stimulating factor, but also may promote the resolution of established infections in conjunction with antibiotics. The therapeutic realities and future therapeutic implications of these agents for the therapy of infections, cancer and hemopoietic disorders are discussed.

  7. Impairment of FOS mRNA stabilization following translation arrest in granulocytes from myelodysplastic syndrome patients.

    Science.gov (United States)

    Feng, Xiaomin; Shikama, Yayoi; Shichishima, Tsutomu; Noji, Hideyoshi; Ikeda, Kazuhiko; Ogawa, Kazuei; Kimura, Hideo; Takeishi, Yasuchika; Kimura, Junko

    2013-01-01

    Although quantitative and qualitative granulocyte defects have been described in myelodysplastic syndromes (MDS), the underlying molecular basis of granulocyte dysfunction in MDS is largely unknown. We recently found that FOS mRNA elevation under translation-inhibiting stimuli was significantly smaller in granulocytes from MDS patients than in healthy individuals. The aim of this study is to clarify the cause of the impaired FOS induction in MDS. We first examined the mechanisms of FOS mRNA elevation using granulocytes from healthy donors cultured with the translation inhibitor emetine. Emetine increased both transcription and mRNA stability of FOS. p38 MAPK inhibition abolished the emetine-induced increase of FOS transcription but did not affect FOS mRNA stabilization. The binding of an AU-rich element (ARE)-binding protein HuR to FOS mRNA containing an ARE in 3'UTR was increased by emetine, and the knockdown of HuR reduced the FOS mRNA stabilizing effect of emetine. We next compared the emetine-induced transcription and mRNA stabilization of FOS between MDS patients and healthy controls. Increased rates of FOS transcription by emetine were similar in MDS and controls. In the absence of emetine, FOS mRNA decayed to nearly 17% of initial levels in 45 min in both groups. In the presence of emetine, however, 76.7±19.8% of FOS mRNA remained after 45 min in healthy controls, versus 37.9±25.5% in MDS (Pknowledge, this is the first report demonstrating attenuation of stress-induced FOS mRNA stabilization in MDS granulocytes.

  8. Phospholipase D catalyzes phospholipid metabolism in chemotactic peptide-stimulated HL-60 granulocytes

    International Nuclear Information System (INIS)

    Pai, J.K.; Siegel, M.I.; Egan, R.W.; Billah, M.M.

    1988-01-01

    There exists circumstantial evidence for activation of phospholipase D (PLD) in intact cells. However, because of the complexity of phospholipid remodeling processes, it is essential to distinguish PLD clearly from other phospholipases and phospholipid remodeling enzymes. Therefore, to establish unequivocally PLD activity in dimethyl sulfoxide-differentiated HL-60 granulocytes, to demonstrate the relative contribution of PLD to phospholipid turnover, and to validate the hypothesis that the formation of phosphatidylethanol is an expression of PLD-catalyzed transphosphatidylation, we have developed methodologies to label HL-60 granulocytes in 1-O-alkyl-2-acyl-sn-glycero-3-phosphocholine (alkyl-PC) with 32P without labeling cellular ATP. These methodologies involve (a) synthesis of alkyl-lysoPC containing 32P by a combination of enzymatic and chemical procedures and (b) incubation of HL-60 granulocytes with this alkyl-[32P] lysoPC which enters the cell and becomes acylated into membrane-associated alkyl-[32P]PC. Upon stimulation of these 32P-labeled cells with the chemotactic peptide, N-formyl-Met-Leu-Phe (fMLP), alkyl-[32P]phosphatidic acid (alkyl-[32P]PA) is formed rapidly. Because, under these conditions, cellular ATP has not been labeled with 32P, alkyl-[32P]PA must be formed via PLD-catalyzed hydrolysis of alkyl-[32P]PC at the terminal phosphodiester bond. This result conclusively demonstrates fMLP-induced activation of PLD in HL-60 granulocytes. These 32P-labeled HL-60 granulocytes have also been stimulated in the presence of ethanol to produce alkyl-[32P]phosphatidylethanol (alkyl-[32P]PEt). Formation of alkyl-[32P]PEt parallels that of alkyl-[32P]PA with respect to time course, fMLP concentration, inhibition by a specific fMLP antagonist (t-butoxycarbonyl-Met-Leu-Phe), and Ca2+ concentration

  9. SEIFEM 2017: from real life to an agreement on the use of granulocyte transfusions and colony-stimulating factors for prophylaxis and treatment of infectious complications in patients with hematologic malignant disorders.

    Science.gov (United States)

    Busca, Alessandro; Cesaro, Simone; Teofili, Luciana; Delia, Mario; Cattaneo, Chiara; Criscuolo, Marianna; Marchesi, Francesco; Fracchiolla, Nicola Stefano; Valentini, Caterina Giovanna; Farina, Francesca; Di Blasi, Roberta; Prezioso, Lucia; Spolzino, Angelica; Candoni, Anna; Del Principe, Maria Ilaria; Verga, Luisa; Nosari, Annamaria; Aversa, Franco; Pagano, Livio

    2018-02-01

    The rapid spread of severe infections mainly due to resistant pathogens, justifies the search for therapies aiming to restore immune functions severely compromised in patients with hematologic malignancies. Areas covered: The present review summarizes the current knowledge on the role of granulocyte transfusions and colony-stimulating factors as treatment strategy for hematologic patients with serious infectious complications. In addition, a survey among 21 hematologic centers, to evaluate the clinical practice for the use of G-CSF originator and biosimilars was performed. Expert commentary: Granulocyte transfusions with a target dose of at least 1.5-3 × 10 8 cells/kg, may be considered as an approach to bridge the gap between marrow suppression and recovery of granulocytes. G-CSF shortens the period of neutropenia, the hospitalization, the use of antibiotics and the rate of febrile neutropenia (FN) in adult and pediatric patients with non-Hodgkin lymphoma, and in adults with acute myeloid leukemia where these advantages nevertheless, did not translate into a clinical benefit. G-CSF biosimilar showed equivalence or non-inferiority to filgrastim. There are no data supporting the use of GM-CSF, eltrombopag and erythropoietin for preventing or treating infectious complications in patients with hematologic disorders.

  10. Tumor-Derived G-CSF Facilitates Neoplastic Growth through a Granulocytic Myeloid-Derived Suppressor Cell-Dependent Mechanism

    Science.gov (United States)

    Waight, Jeremy D.; Hu, Qiang; Miller, Austin; Liu, Song; Abrams, Scott I.

    2011-01-01

    Myeloid-derived suppressor cells (MDSC) are induced under diverse pathologic conditions, including neoplasia, and suppress innate and adaptive immunity. While the mechanisms by which MDSC mediate immunosuppression are well-characterized, details on how they develop remain less understood. This is complicated further by the fact that MDSC comprise multiple myeloid cell types, namely monocytes and granulocytes, reflecting diverse stages of differentiation and the proportion of these subpopulations vary among different neoplastic models. Thus, it is thought that the type and quantities of inflammatory mediators generated during neoplasia dictate the composition of the resultant MDSC response. Although much interest has been devoted to monocytic MDSC biology, a fundamental gap remains in our understanding of the derivation of granulocytic MDSC. In settings of heightened granulocytic MDSC responses, we hypothesized that inappropriate production of G-CSF is a key initiator of granulocytic MDSC accumulation. We observed abundant amounts of G-CSF in vivo, which correlated with robust granulocytic MDSC responses in multiple tumor models. Using G-CSF loss- and gain-of-function approaches, we demonstrated for the first time that: 1) abrogating G-CSF production significantly diminished granulocytic MDSC accumulation and tumor growth; 2) ectopically over-expressing G-CSF in G-CSF-negative tumors significantly augmented granulocytic MDSC accumulation and tumor growth; and 3) treatment of naïve healthy mice with recombinant G-CSF protein elicited granulocytic-like MDSC remarkably similar to those induced under tumor-bearing conditions. Collectively, we demonstrated that tumor-derived G-CSF enhances tumor growth through granulocytic MDSC-dependent mechanisms. These findings provide us with novel insights into MDSC subset development and potentially new biomarkers or targets for cancer therapy. PMID:22110722

  11. Loss of C/EBP alpha cell cycle control increases myeloid progenitor proliferation and transforms the neutrophil granulocyte lineage

    DEFF Research Database (Denmark)

    Porse, Bo T; Bryder, David; Theilgaard-Mönch, Kim

    2005-01-01

    dissociate the ability of C/EBP alpha to block cell cycle progression through E2F inhibition from its function as a transcriptional activator impair the in vivo development of the neutrophil granulocyte and adipose lineages. We now show that such mutations increase the capacity of bone marrow (BM) myeloid...... progenitors to proliferate, and predispose mice to a granulocytic myeloproliferative disorder and transformation of the myeloid compartment of the BM. Both of these phenotypes were transplantable into lethally irradiated recipients. BM transformation was characterized by a block in granulocyte differentiation...

  12. Treatment of blastic transformation of chronic granulocytic leukemia by chemotherapy, total body irradiation and infusion of cryopreserved autologous marrow

    Energy Technology Data Exchange (ETDEWEB)

    Buckner, C D; Stewart, P; Clift, R A; Fefer, A; Neiman, P E; Singer, J; Storb, R; Thomas, E D [Washington Univ., Seattle (USA). School of Medicine; The United States Public Health Service Hospital; Providence Medical Center, and the Fred Hutchinson Cancer Research Center, Seattle, Washington, USA)

    1978-01-01

    We have previously reported attempts to reestablish the chronic phase of chronic granulocytic leukemia (CGL), in two patients with blastic transrormation, utilizing intensive therapy followed by the infusion of cryopreserved autologous marrow. This approach has now been attempted in a total of seven patients. Marrow was harvested on single or multiple occasions during the chronic phase of CGL and cryopreserved in 10% dimethylsulfoxide. All patients were treated with cyclophosphamide, 120 mg/kg, plus 1,000 rad of total body irradiation followed by infusion of stored marrow. Two patients failed to achieve marrow repopulation and died of infection after 29 and 48 days. Three patients had partial marrow recovery. Two of these achieved repopulation of myeloid, erythroid, and lymphoid elements but did not recover platelet function; one died of hemorrhage on day 55, and one died of cytomegalovirus interstitial pneumonitis on day 58. A third patient had delayed engraftment of all cell elements, most prominently lymphocytes, and died after 84 days of an iodopathic interstitial pneumonitis. Two patients achieved prompt and complete reestablishment of the chronic phase of CGL. One died on day 72 with a fungal pheumonitis and one developed blastic transformation within 4 months. These preliminary results indicate that this approach to the treatment of blastic transformation of CGL is feasible but difficult. Improvements in results may be achieved by more frequent storage of marrow and pheripheral blood stem cells and lymphocytes and further advances in pretransplant therapy.

  13. Serological cross-reactivity of Trypanosoma cruzi, Ehrlichia canis, Toxoplasma gondii, Neospora caninum and Babesia canis to Leishmania infantum chagasi tests in dogs

    Directory of Open Access Journals (Sweden)

    Maurício Franco Zanette

    2014-01-01

    Full Text Available Introduction: The aim of this study was to evaluate the serological cross-reactivity between Leishmania sp. and other canine pathogens. Methods: Positive serum samples for Ehrlichia canis, Babesia canis, Toxoplasma gondii, Neospora caninum and Trypanosoma cruzi were tested using three serological methods enzyme linked immunosorbent assay (ELISA, indirect immunofluorescent antibody test (IFAT and Kalazar Detect™, for canine visceral leishmaniasis. Results: Of the 57 dog samples tested, 24 (42.1% tested positive using one of the three serological methods: 10/57 (17.5% for ELISA, 11/57 (19.3% for IFAT and 3/57 (5.3% for Kalazar Detect™. Conclusions: Our results demonstrated that the presence of other infectious agents may lead to cross-reactivity on leishmaniasis serological tests.

  14. Detecção molecular de Ehrlichia canis e Babesia canis vogeli em Rhipicephalus sanguineus sensu lato de carrapatos em Cuba

    Directory of Open Access Journals (Sweden)

    Maylin Gonzalez Navarrete

    2016-12-01

    Full Text Available Os carrapatos (Acari: Ixodidae são de importância médica e veterinária relevantes em todo o mundo por causa da variedade de agentes patogênicos que podem transmitir. No presente trabalho, foi realizada uma pesquisa para identificar Babesia spp. e Ehrlichia spp. em carrapatos coletados de cães de Cuba. Foram coletados 431 carrapatos de 378 cães, tendo sido identificados como pertencentes às espécies de Ripicephalus sanguineus sensu lato (s. 1. O DNA genômico foi extraído com protocolo usando fenol/clorofórmio. Os carrapatos foram organizados em “pools” e o DNA extraído foi testado pela reação em cadeia da polimerase (nPCR para amplificar 398 pares de bases (pb do DNA ribossômico 16S (rDNA de Ehrlichia canis e PCR para amplificar aproximadamente 560 pb do DNA ribossômico 18S (rDNA. Dos 49 pools testados, 8,16% (n = 4/49 foram positivos para o E. canis por nPCR visando o gene do 16S rDNA e apenas um pool (n = 1/49; 2,04% foi positivo para o gene 18S rDNA para Babesia canis. As quatro sequências obtidas para o fragmento de 16S rDNA foram idênticas entre si e resultaram em 100% de identidade com E. canis de diferentes países. A sequência obtida do gene do 18S rDNA para Babesia spp. apresentou semelhança de 100% com Babesia canis vogeli quando comparada às sequências depositadas no Genbank. Esta foi a primeira detecção molecular desses agentes no carrapato R. sanguineus s. l. em Cuba.

  15. Immunoscintigraphic detection of infections using monoclonal antigranulocyte antibodies

    International Nuclear Information System (INIS)

    Seybold, K.

    1988-01-01

    We report on a new approach to in vivo labelling of granulocytes for scintigraphic detection of infections by using the I-123 tagged monoclonal anti-CEA antibody-47 (Mab 47). Mab 47 reacts selectively with a glycoprotein (NAC 95) present on the surface of mature granulocytes. Many in vitro tests showed that binding does not inhibit granulocyte functions (e.g. chemotaxis, initiation of 'burst'). Up till now we have performed the search for infectious lesions in 56 patients. For clinical use one dose consisted of 120 mcg Mab 47 labelled with 148-185 MBq I-123 (specific activity: 1.85 GBq/mg). We noticed that all infectious lesions were highly visible 3-6 hours after tracer infusion or could be excluded after 24 h. High counting rates permitted SPECT-studies up to 24 h p.i. which are very usefull for an exact topographic localization of a lesion. The clinical interest was concentrated on cases of bone and joint infections. It is concluded that there are distinct advantages of the new method compared with In-111 WBC scanning. Without the need for cell separation there is a rapid in vivo labelling of granulocytes so that the method is also suitable in very acute cases. No allergic reactions have been observed. In spite of these obvious advantages and the low administered dose of antibodies we recommend a restriction in immunscintigraphy of infections because of the unknown antigenicity of the compound. (orig.) [de

  16. Short-term exposure of umbilical cord blood CD34+ cells to granulocyte-macrophage colony-stimulating factor early in culture improves ex vivo expansion of neutrophils.

    Science.gov (United States)

    Marturana, Flavia; Timmins, Nicholas E; Nielsen, Lars K

    2011-03-01

    Despite the availability of modern antibiotics/antimycotics and cytokine support, neutropenic infection accounts for the majority of chemotherapy-associated deaths. While transfusion support with donor neutrophils is possible, cost and complicated logistics make such an option unrealistic on a routine basis. A manufactured neutrophil product could enable routine prophylactic administration of neutrophils, preventing the onset of neutropenia and substantially reducing the risk of infection. We examined the use of pre-culture strategies and various cytokine/modulator combinations to improve neutrophil expansion from umbilical cord blood (UCB) hematopoietic stem and progenitor cells (HPC). Enriched UCB HPC were cultured using either two-phase pre-culture strategies or a single phase using various cytokine/modulator combinations. Outcome was assessed with respect to numerical expansion, cell morphology, granulation and respiratory burst activity. Pre-culture in the absence of strong differentiation signals (e.g. granulocyte colony-stimulating factor; G-CSF) failed to provide any improvement to final neutrophil yields. Similarly, removal of differentiating cells during pre-culture failed to improve neutrophil yields to an appreciable extent. Of the cytokine/modulator combinations, the addition of granulocyte-macrophage (GM)-colony-stimulating factor (CSF) alone gave the greatest increase. In order to avoid production of monocytes, it was necessary to remove GM-CSF on day 5. Using this strategy, neutrophil expansion improved 2.7-fold. Although all cytokines and culture strategies employed have been reported previously to enhance HPC expansion, we found that the addition of GM-CSF alone was sufficient to improve total cell yields maximally. The need to remove GM-CSF on day 5 to avoid monocyte differentiation highlights the context and time-dependent complexity of exogenous signaling in hematopoietic cell differentiation and growth.

  17. Polycythemia vera treated with /sup 32/P and myleran: Development of chronic granulocytic leukemia with chromosomal abnormalities in one patient

    Energy Technology Data Exchange (ETDEWEB)

    Stavem, P; Sandnes, K [Rikshospitalet, Oslo (Norway); Hagen, C.B. van der [Oslo Univ. (Norway); Vogt, E [Statens Institutt for Folkehelse, Oslo, Norway

    1975-01-01

    Chronic granulocytic leukemia developed in a 59-year-old woman who had previously received a total of 21 mCl /sup 32/P for polycythemia vera. She was treated with Myleran (busulphan) for her chronic granulocytic leukemia. Cytogenetic studies revealed deletion of chromosomes No. 8 and 12, and translocation between 1 and 8. The patient also developed a severe autoimmune hemolytic anemia, for which she received prednisone treatment. She died with a perforated stomach ulcer. (INIS)

  18. Use of indium-111-oxinate-labelled granulocytes and thrombocytes in kidney transplantation

    International Nuclear Information System (INIS)

    Royen, E.A. van; Schoot, J.B. van der; Hardeman, M.R.; Surachno, S.; Veen, J.H. ten; Vreeken, J.; Wilmink, J.M.

    1981-01-01

    The diagnostic use of 111 In-oxinate-labelled granulocytes and thrombocytes in kidney graft rejection was studied in 39 transplant patients. Normal values were established for the deposition of these cells in stable, functioning kidney grafts. Although some 111 In granulocyte accumulation occurred in the graft during rejection, the increase was too slight to render the method suitable for the early diagnosis of rejection. Significant increased 111 In thrombocyte deposition was found during rejection periods, although large differences were observed in the degree of accumulation. Severity or type of rejection may relate to these differences. Post-transplantation follow-up by 111 In thrombocyte scintigraphy did not result in a much earlier diagnosis of rejection than classic clinical signs. However, more frequent bedside activity determinations might do so. (author)

  19. Efficacy and safety of granulocyte, monocyte/macrophage adsorptive in pediatric ulcerative colitis

    DEFF Research Database (Denmark)

    Ruuska, Tarja; Küster, Peter; Grahnquist, Lena

    2016-01-01

    AIM: To investigate efficacy and safety for granulocyte, monocyte apheresis in a population of pediatric patients with ulcerative colitis. METHODS: The ADAPT study was a prospective, open-label, multicenter study in pediatric patients with moderate, active ulcerative colitis with pediatric...... ulcerative colitis activity index (PUCAI) of 35-64. Patients received one weekly apheresis with Adacolumn(®) granulocyte, monocyte/macrophage adsorptive (GMA) apheresis over 5 consecutive weeks, optionally followed by up to 3 additional apheresis treatments over 3 consecutive weeks. The primary endpoint...... mg daily on average from Baseline to week 12. CONCLUSION: Adacolumn(®) GMA apheresis treatment was effective in pediatric patients with moderate active Ulcerative Colitis. No new safety signals were reported. The present data contribute to considering GMA apheresis as a therapeutic option...

  20. Increased Oxidative Stress Response in Granulocytes from Older Patients with a Hip Fracture May Account for Slow Regeneration

    Directory of Open Access Journals (Sweden)

    Zhiyong Wang

    2014-01-01

    Full Text Available Proximal femur fracture, a typical fracture of the elderly, is often associated with morbidity, reduced quality of life, impaired physical function and increased mortality. There exists evidence that responses of the hematopoietic microenvironment to fractures change with age. Therefore, we investigated oxidative stress markers and oxidative stress-related MAPK activation in granulocytes from the young and the elderly with and without fractured long bones. Lipid peroxidation levels were increased in the elderly controls and patients. Aged granulocytes were more sensitive towards oxidative stress induced damage than young granulocytes. This might be due to the basally increased expression of SOD-1 in the elderly, which was not further induced by fractures, as observed in young patients. This might be caused by an altered MAPK activation. In aged granulocytes basal p38 and JNK activities were increased and basal ERK1/2 activity was decreased. Following fracture, JNK activity decreased, while ERK1/2 and p38 activities increased in both age groups. Control experiments with HL60 cells revealed that the observed p38 activation depends strongly on age. Summarizing, we observed age-dependent changes in the oxidative stress response system of granulocytes after fractures, for example, altered MAPK activation and SOD-1 expression. This makes aged granulocytes vulnerable to the stress stimuli of the fracture and following surgery.

  1. Human Granulocyte Colony-Stimulating Factor (hG-CSF) Expression in Plastids of Lactuca sativa

    OpenAIRE

    Sharifi Tabar, Mehdi; Habashi, Ali Akbar; Rajabi Memari, Hamid

    2013-01-01

    Background: Human granulocyte colony-stimulating factor (hG-CSF) can serve as valuable biopharmaceutical for research and treatment of the human blood cancer. Transplastomic plants have been emerged as a new and high potential candidate for production of recombinant biopharmaceutical proteins in comparison with transgenic plants due to extremely high level expression, biosafety and many other advantages. Methods: hG-CSF gene was cloned into pCL vector between prrn16S promoter and TpsbA ter...

  2. ITAM-like signalling for efficient phagocytosis : The paradigm of the granulocyte receptor CEACAM3

    OpenAIRE

    Pils, Stefan

    2010-01-01

    Human CEACAM3 is a tailor-made receptor of the innate immune system to fight pathogens exploiting epithelial CEACAM-family members for colonisation and invasion of their host. Previous studies established CEACAM3 as the receptor facilitating rapid phagocytosis and elimination of N. gonorrhoeae by human granulocytes. The studies reported here set out to shed light on the evolution of this highly specialised receptor and the associated signalling machinery.CEACAM3 arose from exon shuffling afte...

  3. Assessment of the Total Inflammatory Potential of Bioaerosols by Using a Granulocyte Assay▿

    OpenAIRE

    Timm, Michael; Madsen, Anne Mette; Hansen, Jørgen Vinsløv; Moesby, Lise; Hansen, Erik Wind

    2009-01-01

    Occupational health symptoms related to bioaerosol exposure have been observed in a variety of working environments. Bioaerosols contain microorganisms and microbial components. The aim of this study was to estimate the total inflammatory potential (TIP) of bioaerosols using an in vitro assay based on granulocyte-like cells. A total of 129 bioaerosol samples were collected in the breathing zone of workers during their daily working routine at 22 biofuel plants. The samples were analyzed by tr...

  4. Granulocytes and vascularization regulate uterine bleeding and tissue remodeling in a mouse menstruation model.

    Directory of Open Access Journals (Sweden)

    Astrid Menning

    Full Text Available Menstruation-associated disorders negatively interfere with the quality of life of many women. However, mechanisms underlying pathogenesis of menstrual disorders remain poorly investigated up to date. Among others, this is based on a lack of appropriate pre-clinical animal models. We here employ a mouse menstruation model induced by priming mice with gonadal hormones and application of a physical stimulus into the uterus followed by progesterone removal. As in women, these events are accompanied by menstrual-like bleeding and tissue remodeling processes, i.e. disintegration of decidualized endometrium, as well as subsequent repair. We demonstrate that the onset of bleeding coincides with strong upregulation of inflammatory mediators and massive granulocyte influx into the uterus. Uterine granulocytes play a central role in regulating local tissue remodeling since depletion of these cells results in dysregulated expression of matrix modifying enzymes. As described here for the first time, uterine blood loss can be quantified by help of tampon-like cotton pads. Using this novel technique, we reveal that blood loss is strongly reduced upon inhibition of endometrial vascularization and thus, is a key regulator of menstrual bleeding. Taken together, we here identify angiogenesis and infiltrating granulocytes as critical determinants of uterine bleeding and tissue remodeling in a mouse menstruation model. Importantly, our study provides a technical and scientific basis allowing quantification of uterine blood loss in mice and thus, assessment of therapeutic intervention, proving great potential for future use in basic research and drug discovery.

  5. Immature granulocyte detection by the SE-9000 haematology analyser during pregnancy.

    Science.gov (United States)

    Fernández-Suárez, A; Pascual, V T; Gimenez, M T F; Hernández, J F S

    2003-12-01

    The objective of this study was to determine the nature of the alarm for immature granulocytes appearing in haemograms from pregnant women, as detected by the immature cell information channel (IMI) of the SE-9000 automated haematology analyser. Of all tests run on pregnant women in a 4-month period (n = 698), the first 100 haemograms with immature granulocyte alarms (14.33%) were collected. Each of these samples was then stained with Wright-Giemsa stain. The following variables were also analysed: age of the mother, trimester and days of gestation, type of delivery, weight and sex of the baby, and Apgar score. Most pregnant women were in the third trimester of gestation (82%) when an alarm was noted on the IMI channel. Of the patients, 62% had normal deliveries. The most frequent complication was obstructed delivery (23%). Mean percentages by microscopic counts of band cells, metamyelocytes, and myelocytes were 2.99, 0.45, and 0.19%, respectively. There was a statistically significant correlation for all cell types between the SE-9000 and the manual count method. No association was observed between the presence of immature granulocytes and the clinical variables analysed. The SE-9000 analyser shows high sensitivity in the IMI channel for detection of immature forms.

  6. Radionuclides and inflammatory bowel diseases: 99mTc-sucralfate and 111 In-tropolonate-granulocytes

    International Nuclear Information System (INIS)

    Deveaux, M.; Macaigne, O.; Lecouffe, P.; Hossein-Foucher, CL.; Meuriot, S.; Venel, H.; Cortot, A.; Marchandise, X.

    1989-01-01

    111 In-tropolonate-granulocytes (G- 111 In) study was performed in 16 patients with inflammatory bowel disease (IBD). Images were obtained 3 h and 20 h post-injection. Counting of four days feacal excretion was more accurately expressed as daily intestinal granulocytes clearance. The day before, 12 of the patients had a sucralfate- 99m Tc scan (S- 99m Tc). Correlation between radioendoscopic data and S- 99m Tc scans was poor in 9 instances and there was no correlation between scan activity index and clinical and biological assessment. Correlation between G- 111 In scans and radioendoscopic data was excellent in 13 instances. Scan activity index was correlated with the Best index and with the intestinal alpha-1-antitrypsine clearance. Faecal excretion (range. 1 - 40%) and daily intestinal granulocytes clearance values (range. 03 - 50 milliards) were only correlated with protein loss parameters. So S- 99m Tc scan does not appear to be reliable, while intestinal G- 111 In clearance, not such easy to perform, can give an accurate assessment of IBD activity [fr

  7. Effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors

    International Nuclear Information System (INIS)

    Cronkite, E.P.; Carsten, A.L.; Cohen, R.; Miller, M.E.; Moccia, G.

    1978-01-01

    The purpose of these studies was to evaluate the effects of humoral factors on amplification of nonrecognizable erythrocytic and granulocytic precursors using the in vivo plasma clot diffusion chamber and the in vitro plasma clot culture methods. Plasma erythropoietin levels changes in the reticulocyte concentration and hematocrits of irradiated and non-irradiated Long-Evans rats exposed to hypoxia were also determined. While erythropoietin plasma levels appeared to effect BFU-E and CFU-E growth, results suggest erythropoietin may not be the sole regulator of red cell production and that inhibitors or chalone-like mechanisms may be involved. Measurements made on granulocyte precursors treated with CSF containing L-cell conditioned medium revealed granulocytic colonies and burst-like formations, similar to those seen for erythrocytic growth. There is strong evidence suggesting that CSF is a regulator of granulopoiesis; however, it is not the sole regulator and it appears that inhibitors may play an in vivo role. Growth of colonies with cell numbers not a power of 2 implies either asymmetric nitosis due to loss of genetic information required for continuing division, or differences in concentration of, or ability to recognize inhibitory factors. These possibilities are examined on the basis of results using in vivo and in vitro culture techniques

  8. Increased granulocytic, erythrocytic, and megakaryocytic progenitors in myelofibrosis with myeloid metaplasia

    International Nuclear Information System (INIS)

    Chikkappa, G.; Carsten, A.L.; Chanana, A.D.; Chandra, P.; Cronkite, E.P.

    1978-01-01

    Nucleated cells obtained from blood and/or bone marrow of patients with myelofibrosis with myeloid metaplasia (MMM) were cultured in diffusion chambers (DC) implanted into the peritoneal cavities of irradiated mice. A total of five blood studies and two bone marrow studies were performed using cells obtained from five patients. The DC were harvested at intervals from the host mice and the total and differential cellularity of DC contents were evaluated. The results obtained from MMM cultures were compared with those from similar cultures of blood cells and marrow cells of four and six normal individuals respectively. The proliferation and maturation of the granulocytic, erythrocytic, and megakaryocytic lines in MMM cultures occurred in an orderly fashion as they occur in vivo. The patterns of proliferation and maturation of the three cell lines in cultures after day 7 suggest that they primarily originate from progenitor cells. The numbers of granulocytes in the multiplicative pool, recognizable red cell precursors, and megakaryocytes recovered were significantly greater from the MMM cultures than those from the normal blood or marrow cultures. These results suggest that the blood and marrow cells of MMM patients have increased numbers of progenitors for granulocytes, erythrocytes and megakaryocytes

  9. Investigação molecular de Ehrlichia spp. e Anaplasma platys em felinos domésticos: alterações clínicas, hematológicas e bioquímicas

    Directory of Open Access Journals (Sweden)

    Elisabete S Correa

    2011-10-01

    Full Text Available Ehrlichia sp. e Anaplasma platys são micro-organismos Gram negativos, parasitos intracelulares obrigatórios, residindo em vacúolos citoplasmáticos de leucócitos e plaquetas, encontrados no sangue periférico ou em tecidos. Poucos relatos têm sido feitos sobre erliquiose e anaplasmose em gatos no Brasil, os quais são baseados na presença de mórulas em leucócitos e plaquetas, ou pela detecção de anticorpos. O objetivo deste trabalho foi investigar a infecção natural por Ehrlichia sp. e A.platys em gatos no Município de Campos dos Goytacazes-RJ, através da hematoscopia e pela detecção do DNA desses agentes. Foram utilizadas amostras de sangue total e de soro de 91 gatos, independente de raça, sexo e idade. Realizaram-se hemograma, bioquímica sérica e PCR, utilizando oligonucleotídes para Ehrlichia sp. e A.platys. Os dados de hematoscopia mostraram que 9,89% dos gatos apresentaram mórulas em macroplaquetas. O DNA de A.platys foi detectado em 13,18% dos 91 animais e em 44,44% das amostras positivas à hematoscopia. O DNA de Ehrlichia sp. não foi detectado em nenhuma amostra. Nenhuma alteração foi observada nos sinais clínicos nem nos resultados laboratoriais nos animais estudados. Os dados sugerem que os felinos domésticos podem atuar como potenciais reservatórios para A. platys, como forma não sintomática das enfermidades relacionadas

  10. Prevalence of Ehrlichia canis using the nested-PCR, correlation with the presence of morulae and thrombocytopenia in dogs treated in Veterinary Hospital of the Federal University of Espirito Santo

    Directory of Open Access Journals (Sweden)

    Mara Rúbia Rocha Pereira Sales

    2015-03-01

    Full Text Available ABSTRACT. Sales M.R.R.P., Ignacchiti M.D.C., Mendes Junior A.F., Suhett W.G., Porfírio L.C., Marins M., Aptekmann K.P. & Pereira Júnior O.S. [Prevalence of Ehrlichia canis using the nested-PCR, correlation with the presence of morulae and thrombocytopenia in dogs treated in Veterinary Hospital of the Federal University of Espirito Santo.] Prevalência de Ehrlichia canis pela Nested- -PCR, correlação com a presença de mórula e trombocitopenia em cães atendidos no Hospital Veterinário da Universidade Federal do Espírito Santo. Revista Brasileira de Medicina Veterinária, 37(1:47-51, 2015. Centro de Ciências Agrárias, Universidade Federal do Espírito Santo, Rua Projetada s/nº, Caixa Postal 25, Pontal, Marataízes, ES 29349-000, Brasil. E-mail: mararrps@yahoo.com.br Ehrlichia canis, is the primary etiologic agent of canine monocytic ehrlichiosis. The disease is mainly transmitted by the brown dog ticks Rhipicephalus sanguineus in different endemic regions of Brazil. The purpose of this study was determinated using the Nested Polymerase Chain Reaction (nested-PCR the prevalence of Ehrlichia canis in 85 dogs, regardless of race, age, sex or health status, treated at the Veterinary Hospital of Federal University of Espirito Santo, in Alegre-ES and evaluate its correlation with the presence of morulae and thrombocytopenia. It was observed that 1.17% of the samples were positive by blood smear, for the presence of morulae. However, the nested-PCR showed 5.88% positivity of samples. And 17.64% samples showed thrombocytopenia. By analyzing all the techniques, it was concluded that the introduction of diagnostic techniques such as nested-PCR is an important method for aid in early diagnosis of pathologies.

  11. Interferon-alpha suppressed granulocyte colony stimulating factor production is reversed by CL097, a TLR7/8 agonist.

    LENUS (Irish Health Repository)

    Tajuddin, Tariq

    2012-02-01

    BACKGROUND AND AIM: Neutropenia, a major side-effect of interferon-alpha (IFN-alpha) therapy can be effectively treated by the recombinant form of granulocyte colony stimulating factor (G-CSF), an important growth factor for neutrophils. We hypothesized that IFN-alpha might suppress G-CSF production by peripheral blood mononuclear cells (PBMCs), contributing to the development of neutropenia, and that a toll-like receptor (TLR) agonist might overcome this suppression. METHODS: Fifty-five patients who were receiving IFN-alpha\\/ribavirin combination therapy for chronic hepatitis C virus (HCV) infection were recruited. Absolute neutrophil counts (ANC), monocyte counts and treatment outcome data were recorded. G-CSF levels in the supernatants of PBMCs isolated from the patients and healthy controls were assessed by enzyme-linked immunosorbent assay following 18 h of culture in the absence or presence of IFN- alpha or the TLR7\\/8 agonist, CL097. RESULTS: Therapeutic IFN-alpha caused a significant reduction in neutrophil counts in all patients, with 15 patients requiring therapeutic G-CSF. The reduction in ANC over the course of IFN-alpha treatment was paralleled by a decrease in the ability of PBMCs to produce G-CSF. In vitro G-CSF production by PBMCs was suppressed in the presence of IFN-alpha; however, co-incubation with a TLR7\\/8 agonist significantly enhanced G-CSF secretion by cells obtained both from HCV patients and healthy controls. CONCLUSIONS: Suppressed G-CSF production in the presence of IFN-alpha may contribute to IFN-alpha-induced neutropenia. However, a TLR7\\/8 agonist elicits G-CSF secretion even in the presence of IFN-alpha, suggesting a possible therapeutic role for TLR agonists in treatment of IFN-alpha-induced neutropenia.

  12. Granulocyte Colony-Stimulating Factor Combined with Methylprednisolone Improves Functional Outcomes in Rats with Experimental Acute Spinal Cord Injury

    Directory of Open Access Journals (Sweden)

    William Gemio Jacobsen Teixeira

    2018-02-01

    Full Text Available OBJECTIVES: To evaluate the effects of combined treatment with granulocyte colony-stimulating factor (G-CSF and methylprednisolone in rats subjected to experimental spinal cord injury. METHODS: Forty Wistar rats received a moderate spinal cord injury and were divided into four groups: control (no treatment; G-CSF (G-CSF at the time of injury and daily over the next five days; methylprednisolone (methylprednisolone for 24 h; and G-CSF/Methylprednisolone (methylprednisolone for 24 h and G-CSF at the time of injury and daily over the next five days. Functional evaluation was performed using the Basso, Beattie and Bresnahan score on days 2, 7, 14, 21, 28, 35 and 42 following injury. Motor-evoked potentials were evaluated. Histological examination of the spinal cord lesion was performed immediately after euthanasia on day 42. RESULTS: Eight animals were excluded (2 from each group due to infection, a normal Basso, Beattie and Bresnahan score at their first evaluation, or autophagy, and 32 were evaluated. The combination of methylprednisolone and G-CSF promoted greater functional improvement than methylprednisolone or G-CSF alone (p<0.001. This combination also exhibited a synergistic effect, with improvements in hyperemia and cellular infiltration at the injury site (p<0.001. The groups displayed no neurophysiological differences (latency p=0.85; amplitude p=0.75. CONCLUSION: Methylprednisolone plus G-CSF promotes functional and histological improvements superior to those achieved by either of these drugs alone when treating spinal cord contusion injuries in rats. Combining the two drugs did have a synergistic effect.

  13. CD1 molecule expression on human monocytes induced by granulocyte-macrophage colony-stimulating factor.

    Science.gov (United States)

    Kasinrerk, W; Baumruker, T; Majdic, O; Knapp, W; Stockinger, H

    1993-01-15

    In this paper we demonstrate that granulocyte-macrophage CSF (GM-CSF) specifically induces the expression of CD1 molecules, CD1a, CD1b and CD1c, upon human monocytes. CD1 molecules appeared upon monocytes on day 1 of stimulation with rGM-CSF, and expression was up-regulated until day 3. Monocytes cultured in the presence of LPS, FMLP, PMA, recombinant granulocyte-CSF, rIFN-gamma, rTNF-alpha, rIL-1 alpha, rIL-1 beta, and rIL-6 remained negative. The induction of CD1 molecules by rGM-CSF was restricted to monocytes, since no such effect was observed upon peripheral blood granulocytes, PBL, and the myeloid cell lines Monomac1, Monomac6, MV4/11, HL60, U937, THP1, KG1, and KG1A. CD1a mRNA was detectable in rGM-CSF-induced monocytes but not in those freshly isolated. SDS-PAGE and immunoblotting analyses of CD1a mAb VIT6 immunoprecipitate from lysate of rGM-CSF-activated monocytes revealed an appropriate CD1a polypeptide band of 49 kDa associated with beta 2-microglobulin. Expression of CD1 molecules on monocytes complements the distribution of these structures on accessory cells, and their specific induction by GM-CSF strengthens the suggestion that CD1 is a family of crucial structures required for interaction between accessory cells and T cells.

  14. Hematological importance of pseudoeosinophilic granulocytes in acclimation of common carp (Cyprinus carpio Linnaeus, 1758

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    Damir Suljevic

    2017-03-01

    Full Text Available Adaptation mechanisms as response to water content, oxygen level and pollutants are very important and they can be interpreted by hematological analysis. The aim of this study was the analysis of hematological and immune adaptations of common carp (Cyprinus carpio Linnaeus, 1758 to thermal stress. All specimens were divided into a control and experimental group. The control group of fish was exposed to a constant water temperature of 10°C. We induced thermal stress in experimental fish by gradually heating water to 28°C, held for 30 minutes and then comparing the obtained results with the control fish. Short-term hyperthermia lead to an increase of the number of leukocytes, especially pseudoeosinophilic granulocytes and monocytes, while the number of neutrophils and lymphocytes was reduced. The analysis of the leukocyte number and differential blood count in the control group showed high individual variation of segmented granulocytes, monocytes and pseudoeosinophilic granulocytes. Statistically significant differences (p=0.00 were found for the white blood cells, nonsegmented neutrophils and pseudoeosinophils between the control and experimental group. The experimental group of males had an increased number of white blood cells, monocytes and pseudoeosinophils, where significant differences were found for nonsegmented and total neutrophils and also for pseudoeosinophils (p=0.00, lymphocytes (p=0.01 and monocytes (p=0.03. Females had an increased total number of white blood cells, lymphocytes, monocytes and pseudoeosinophils, while significant differences (p=0.00 were obtained in the number of white blood cells, non segmented and total neutrophils and pseudoeosinophils between the control and experimental group. Adaptation mechanisms in carp after water temperature heating are mostly reflected in the increase of pseudoeosinophils and the decrease of neutrophils.

  15. Cytotoxic immigration of granulocytes into megakaryocytes as a late consequence of irradiation

    International Nuclear Information System (INIS)

    Calvo, W.; Alabi, R.; Nothdurft, W.; Fliedner, T.M.

    1994-01-01

    The immigration of neutrophilic granulocytes into megakaryocyte was studied in the bone marrow of normal and X-irradiated beagle under various exposure conditions. Two groups of dogs received homogeneous total-body irradiation. One group received a dose of 1.6 Gy and the other received a dose of 2.4 Gy (midline tissue). A third group was irradiated from the left side of the body only. This exposure resulted in an inhomogeneous total-body irradiation (entrance dose 3.8 Gy, exit dose 0.9 Gy). A fourth group of animals received partial-body irradiation with a dose of 11.7 Gy delivered to the anterior two-thirds of the body, thereby subjecting about 70% of the hemopoietic marrow to irradiation. Dogs of a fifth group remained unexposed to irradiation and served as controls. The marrow was analyzed in sections of the ribs approximately 1 year after irradiation. The total number of megakaryocytes in one section was evaluated. The number of megakaryocytes showing granulocytes in their cytoplasm was determined and expressed as a percentage. This phenomenon can be explained as cytotoxic immigration of granulocytes into megakaryocytes. It was observed in approximately 1-2 of the megakaryocytes in the marrow of normal dogs. One year after irradiation the value increased of normal dogs. One year after irradiation the value increased to 10-26%. It was observed that neutrophilic granuloytes penetrated only into the large mature megakaryocytes in which the nuclei were most pyknotic. This phenomenon may be considered as a late effect of irradiation. 15 refs., 4 figs., 2 tabs

  16. Recurrent spleen enlargement during cyclic granulocyte-macrophage colony-stimulating factor therapy for myelodysplastic syndrome

    International Nuclear Information System (INIS)

    Delmer, A.; Karmochkine, M.; Cadiou, M.; Gerhartz, H.; Zittoun, R.

    1990-01-01

    A 65-year-old woman with refractory anemia with excess of blasts received sequential courses of granulocyte-macrophage colony-stimulating factor therapy (GM-CSF) and low-dose cytosine arabinoside. Each course of GM-CSF induced a rapid and tremendous increase in leukocyte count as well as in spleen size, 111-indium chloride scanning suggested a myeloid metaplasia of the spleen. This observation suggests that in some patients the granulopoietic response to the myeloid growth factor stimulation may be predominant in the spleen

  17. Methylation of histones in myeloid leukemias as a potential marker of granulocyte abnormalities

    Czech Academy of Sciences Publication Activity Database

    Lukášová, Emilie; Kořistek, Z.; Falk, Martin; Kozubek, Stanislav; Grigoryev, S.; Kozubek, Michal; Ondřej, Vladan; Kroupová, I.

    2005-01-01

    Roč. 77, č. 1 (2005), s. 1-12 ISSN 0741-5400 R&D Projects: GA MZd NC6987; GA AV ČR(CZ) IAA1065203; GA AV ČR(CZ) KSK5052113; GA AV ČR(CZ) IBS5004010; GA ČR(CZ) GA202/02/0804; GA MŠk ME 565 Institutional research plan: CEZ:AV0Z50040507 Keywords : human granulocytes differentiation * chromatin condensation * heterochromatin Subject RIV: BO - Biophysics Impact factor: 4.627, year: 2005

  18. STAT3 activation and infiltration of eosinophil granulocytes in mycosis fungoides

    DEFF Research Database (Denmark)

    Fredholm, Simon; Gjerdrum, Lise Mette R; Willerslev-Olsen, Andreas

    2014-01-01

    Eosinophil granulocytes have been implicated in anticancer immunity but recent data indicate that eosinophils can also promote cancer. Herein, we studied eosinophils in skin lesions from 43 patients with mycosis fungoides (MF). The presence of eosinophils correlated with disease stage: 78......% of patients with advanced disease displayed eosinophil infiltration, whereas this was only seen in 11% of patients with patches (p...) in malignant T-cells also stained positively for eosinophils, whereas this was only observed in 28% of pY-STAT3-negative patients (peosinophilic activation and trafficking factors: High-mobility group BOX-1 protein (HMGB1) and interleukin 5 (IL5). STAT3 si...

  19. Second case of chronic granulocytic leukemia with karyotypic evolution at acute crisis, occurring in so-called Nishiyama district

    Energy Technology Data Exchange (ETDEWEB)

    Yao, E; Tomonaga, Yu; Nishino, K; Matsunaga, M; Sadamori, N [Nagasaki Univ. (Japan). School of Medicine

    1978-09-01

    The whole process of a second case of chronic granulocytic leukemia in Nishiyama district where a very small amount of radiation existed for a long time was reported together with data measured by a human counter and the results of chromosomal analysis. No significantly high K or /sup 137/Cs values were measured by a human counter immediately after the onset. Chromosomal division aberration and chromosomal aberration, which seemed to be induced by radiation, also were not observed. However, granulocytic leukemia was diagnosed after chromosomal analysis of peripheral blood revealed Ph/sup 1/ chromosomes, white cell count increased, juvenile cells appeared, and basophil cells increased. Clinical features of typical chronic granulocytic leukemia in the exposed were observed during the chronic stage (7 years). In the acute stage, abnormal clones were discovered in all 16 chromosomes analyzed. Much karyotypic evolution identical to that in persons directly exposed to the A-bomb was also observed.

  20. Synthesis, structural characterization and effect on human granulocyte intracellular cAMP levels of abscisic acid analogs.

    Science.gov (United States)

    Bellotti, Marta; Salis, Annalisa; Grozio, Alessia; Damonte, Gianluca; Vigliarolo, Tiziana; Galatini, Andrea; Zocchi, Elena; Benatti, Umberto; Millo, Enrico

    2015-01-01

    The phytohormone abscisic acid (ABA), in addition to regulating physiological functions in plants, is also produced and released by several mammalian cell types, including human granulocytes, where it stimulates innate immune functions via an increase of the intracellular cAMP concentration ([cAMP]i). We synthesized several ABA analogs and evaluated the structure-activity relationship, by the systematical modification of selected regions of these analogs. The resulting molecules were tested for their ability to inhibit the ABA-induced increase of [cAMP]i in human granulocytes. The analogs with modified configurations at C-2' and C-3' abrogated the ABA-induced increase of the [cAMP]i and also inhibited several pro-inflammatory effects induced by exogenous ABA on granulocytes and monocytes. Accordingly, these analogs could be suitable as novel putative anti-inflammatory compounds. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. High throughput pyrosequencing technology for molecular differential detection of Babesia vogeli, Hepatozoon canis, Ehrlichia canis and Anaplasma platys in canine blood samples.

    Science.gov (United States)

    Kaewkong, Worasak; Intapan, Pewpan M; Sanpool, Oranuch; Janwan, Penchom; Thanchomnang, Tongjit; Kongklieng, Amornmas; Tantrawatpan, Chairat; Boonmars, Thidarut; Lulitanond, Viraphong; Taweethavonsawat, Piyanan; Chungpivat, Sudchit; Maleewong, Wanchai

    2014-06-01

    Canine babesiosis, hepatozoonosis, ehrlichiosis, and anaplasmosis are tick-borne diseases caused by different hemopathogens. These diseases are causes of morbidity and mortality in dogs. The classic method for parasite detection and differentiation is based on microscopic observation of blood smears. The limitations of the microscopic method are that its performance requires a specially qualified person with professional competence, and it is ineffective in differentiating closely related species. This study applied PCR amplification with high throughput pyrosequencing for molecular differential detection of the following 4 hemoparasites common to tropical areas in dog blood samples: Babesia vogeli, Hepatozoon canis, Ehrlichia canis, and Anaplasma platys. PCR was initially used to amplify specific target regions of the ribosomal RNA genes of each parasite using 2 primer pairs that included 18S rRNA for protozoa (B. vogeli and H. canis) and 16S rRNA for rickettsia (E. canis and A. platys). Babesia vogeli and H. canis were discriminated using 9 nucleotide positions out of 30 base pairs, whereas E. canis and A. platys were differentiated using 15 nucleotide positions out of 34 base pairs that were determined from regions adjacent to 3' ends of the sequencing primers. This method provides a challenging alternative for a rapid diagnosis and surveillance of these tick-borne diseases in canines. Copyright © 2014 Elsevier GmbH. All rights reserved.

  2. Determination and quantification of the in vitro activity of Aloe marlothii (A. Berger subsp. marlothii and Elephantorrhiza elephantina (Burch. skeels acetone extracts against Ehrlichia ruminantium

    Directory of Open Access Journals (Sweden)

    V. Naidoo

    2006-09-01

    Full Text Available An Ehrlichia ruminantium culture system was utilized for the anti-rickettsial evaluation of two ethnoveterinary plants, Elephantorrhiza elephantina and Aloe marlothii. Well-established E. ruminantium cultures were incubated with the plant leaf acetone extracts and compared to oxytetracycline and untreated controls. Effectivity was established by comparing the percentage parasitised cells and the calculation of both EC50 and extrapolated EC90 in µg/ml. The plant extracts were also screened for antibacterial activity using bioautography. Elephantorrhiza elephantina and A. marlothii demonstrated anti-ehrlichial activity with an EC50 of 111.4 and 64.5 µg/ml and EC 90 of 228.9 and 129.9 µg/ml, respectively. The corresponding EC50 and EC90 for oxytetracycline was 0.29 and 0.08 µg/ml. Both plants appeared to produce their inhibitory activity by a similar mechanism, unrelated to that of the tetracyclines. Both the plant acetone extracts demonstrated antibacterial activity against Escherichia coli and Staphylococcus aureus (ATCC strains.

  3. Elevated Systemic Levels of Eosinophil, Neutrophil, and Mast Cell Granular Proteins in Strongyloides Stercoralis Infection that Diminish following Treatment.

    Science.gov (United States)

    Rajamanickam, Anuradha; Munisankar, Saravanan; Bhootra, Yukthi; Dolla, Chandra Kumar; Nutman, Thomas B; Babu, Subash

    2018-01-01

    Infection with the helminth parasite Strongyloides stercoralis ( Ss ) is commonly clinically asymptomatic that is often accompanied by peripheral eosinophilia. Granulocytes are activated during helminth infection and can act as immune effector cells. Plasma levels of eosinophil and neutrophil granular proteins convey an indirect measure of granulocyte degranulation and are prominently augmented in numerous helminth-infected patients. In this study, we sought to examine the levels of eosinophil, neutrophil, and mast cell activation-associated granule proteins in asymptomatic Ss infection and to understand their kinetics following anthelmintic therapy. To this end, we measured the plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, neutrophil elastase, myeloperoxidase, neutrophil proteinase-3, mast cell tryptase, leukotriene C4, and mast cell carboxypeptidase-A3 in individuals with asymptomatic Ss infection or without Ss infection [uninfected (UN)]. We also estimated the levels of all of these analytes in infected individuals following definitive treatment of Ss infection. We demonstrated that those infected individuals have significantly enhanced plasma levels of eosinophil cationic protein, eosinophil-derived neurotoxin, eosinophil peroxidase, eosinophil major basic protein, elastase, myeloperoxidase, mast cell tryptase, leukotriene C4, and carboxypeptidase-A3 compared to UN individuals. Following the treatment of Ss infection, each of these granulocyte-associated proteins drops significantly. Our data suggest that eosinophil, neutrophil, and mast cell activation may play a role in the response to Ss infection.

  4. A randomized clinical trial to evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium for in vitro fertilization

    DEFF Research Database (Denmark)

    Ziebe, Søren; Loft, Anne; Povlsen, Betina B

    2013-01-01

    To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR).......To evaluate the effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) in embryo culture medium on ongoing implantation rate (OIR)....

  5. Recombinant granulocyte colony-stimulating factor administered enterally to neonates is not absorbed.

    Science.gov (United States)

    Calhoun, Darlene A; Maheshwari, Akhil; Christensen, Robert D

    2003-08-01

    Granulocyte colony-stimulating factor (G-CSF) is present in liquids swallowed by the fetus and neonate; specifically, amniotic fluid, colostrum, and human milk. The swallowed G-CSF has local effects on enteric cells, which express the G-CSF receptor. However, some portion of the G-CSF ingested by the fetus and neonate might be absorbed into the circulation and have systemic actions, such as stimulating neutrophil production. To assess this possibility we sought to determine if circulating G-CSF concentrations of neonates increase after enteral administration of recombinant human granulocyte colony-stimulating factor (rhG-CSF). This was a single-center, prospective, blinded, randomized, 2 x 2 crossover study, with each infant receiving 1 dose of rhG-CSF (100 microg/kg) and 1 dose of placebo. Plasma G-CSF concentrations were measured at 2 and 4 hours after administration of the test solution. No significant change in plasma G-CSF concentration was observed after the enteral administration of rhG-CSF. On this basis, we conclude that orally administered rhG-CSF is not absorbed in significant quantities, and we speculate that the G-CSF swallowed by the fetus and neonate has local but not systemic effects.

  6. Sweet’s Syndrome Successfully Treated with Granulocyte and Monocyte Adsorption Apheresis

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    Asami Fujii

    2017-05-01

    Full Text Available Sweet’s syndrome is a neutrophilic dermatosis characterized by an abrupt onset of painful erythematous lesions showing neutrophilic infiltrates in the dermis. Fever and an elevated neutrophil level are generally observed. Sweet’s syndrome may be idiopathic, malignancy-associated, or drug-induced (mainly involving granulocyte colony-stimulating factor (G-CSF administration. Although systemic corticosteroids are usually effective, the symptoms of Sweet’s syndrome recur in some refractory cases. Herein, we report a case of a 55-year-old Japanese woman with recurrent symptoms of fever (>39°C and painful erythematous lesions on her four extremities, trunk, and neck. Laboratory findings revealed leukocytosis and high levels of C-reactive protein (CRP and G-CSF. She was diagnosed with a recurrence of Sweet’s syndrome, and was exclusively treated with granulocyte and monocyte adsorption apheresis (GMA therapy once a week for 3 consecutive weeks. After the first session of GMA therapy, all symptoms including the erythematous lesions and fever were completely resolved, and serum G-CSF level was reduced. Leukocyte count, neutrophil count, serum amyloid A protein, and CRP levels were restored within normal ranges by 2 weeks. Thus, GMA therapy can successfully treat a patient with recurrent Sweet’s syndrome, potentially related to the restoration of elevated serum G-CSF levels.

  7. Prevention of myelosuppression by combined treatment with enterosorbent and granulocyte colony-stimulating factor.

    Science.gov (United States)

    Shevchuk, O O; Posokhova, К А; Todor, I N; Lukianova, N Yu; Nikolaev, V G; Chekhun, V F

    2015-06-01

    Hematotoxicity and its complication are the prominent limiting factors for rational treatment of malignancies. Granulocyte colony-stimulating factor (G-CSF) is used to increase granulocyte production. It has been shown previously that enterosorption causes prominent myeloprotective activity also. Still, no trial was performed to combine both of them. To study the influence of combination of enterosorption and pharmaceutical analogue of naturally occurring G-CSF (filgrastim) on bone marrow protection and the growth of grafted tumor in a case of injection of melphalan (Mel). Mel injections were used for promotion of bone marrow suppression in rats. Carbon granulated enterosorbent C2 (IEPOR) was used for providing of enteral sorption detoxifying therapy. Filgrastim was used to increase white blood cells (WBC) count. The simultaneous usage of enterosorption and filgrastim had maximum effectiveness for restoring of all types of blood cells. WBC count was higher by 138.3% compared with the Mel group. The increase of platelets count by 98.5% was also observed. In the group (Mel + C2 + filgrastim) the absolute neutrophils count was twofold higher, in comparison with rats of Mel group. Simultaneous administration of G-CSF-analogue and carbonic enterosorbent C2 is a perspective approach for bone marrow protection, when the cytostatic drug melphalan is used. Such combination demonstrates prominent positive impact on restoring of all types of blood cells and had no influence on the antitumor efficacy.

  8. (±)-2-Chloropropionic acid elevates reactive oxygen species formation in human neutrophil granulocytes

    International Nuclear Information System (INIS)

    Aam, B.B.; Fonnum, F.

    2006-01-01

    (±)-2-Chloropropionic acid (2-CPA) is a neurotoxic compound which kills cerebellar granule cells in vivo, and makes cerebellar granule cells in vitro produce reactive oxygen species (ROS). We have studied the effect of 2-CPA on ROS formation in human neutrophil granulocytes in vitro. We found an increased formation of ROS after 2-CPA exposure using three different methods; the fluorescent probe DCFH-DA and the chemiluminescent probes lucigenin and luminol. Four different inhibitors of ROS formation were tested on the cells in combination with 2-CPA to characterize the signalling pathways. The spin-trap s-PBN, the ERK1/2 inhibitor U0126 and the antioxidant Vitamin E inhibited the 2-CPA-induced ROS formation completely, while the mitochondrial transition permeability pore blocker cyclosporine A inhibited the ROS formation partly. We also found that 2-CPA induced an increased nitric oxide production in the cells by using the Griess reagent. The level of reduced glutathione, measured with the DTNB assay, was decreased after exposure to high concentrations of 2-CPA. Western blotting analysis showed that 2-CPA exposure led to an elevated phosphorylation of ERK MAP kinase. This phosphorylation was inhibited by U0126. Based on these experiments it seems like the mechanisms for 2-CPA induced toxicity involves ROS formation and is similar in neutrophil granulocytes as earlier shown in cerebellar granule cells. This also implies that 2-CPA may be immunotoxic

  9. The Effect of Recombinant Granulocyte Colony-Stimulating Factor on Oral and Periodontal Manifestations in a Patient with Cyclic Neutropenia: A Case Report

    Directory of Open Access Journals (Sweden)

    Sergio Matarasso

    2009-01-01

    Full Text Available Cyclic Neutropenia (CN is characterized by recurrent infections, fever, oral ulcerations, and severe periodontitis as result of the reduced host defences. The previous studies have established the effectiveness of recombinant granulocyte colony-stimulating factor (GCSF to increase the number and the function of neutrophils in the peripheral blood in this disease. In a 20-year-old Caucasian female with a diagnosis of cyclic neutropenia, oral clinical examination revealed multiple painful ulcerations of the oral mucosa, poor oral hygiene conditions, marginal gingivitis, and moderate periodontitis. The patient received a treatment with G-CSF (Pegfilgrastim, 6 mg/month in order to improve her immunological status. Once a month nonsurgical periodontal treatment was carefully performed when absolute neutrophil count (ANC was ≥500/L. The treatment with G-CSF resulted in a rapid increase of circulating neutrophils that, despite its short duration, leaded to a reduction in infection related events and the resolution of the multiple oral ulcerations. The disappearance of oral pain allowed an efficacy nonsurgical treatment and a normal tooth brushing that determined a reduction of probing depth (PD≤4 mm and an improvement of the oral hygiene conditions recorded at 6-month follow-up.

  10. Co-expression of HIV-1 virus-like particles and granulocyte-macrophage colony stimulating factor by GEO-D03 DNA vaccine

    Science.gov (United States)

    Hellerstein, Michael; Xu, Yongxian; Marino, Tracie; Lu, Shan; Yi, Hong; Wright, Elizabeth R.; Robinson, Harriet L.

    2012-01-01

    Here, we report on GEO-D03, a DNA vaccine that co-expresses non-infectious HIV-1 virus-like particles (VLPs) and the human cytokine, granulocyte-macrophage colony-stimulating factor (GM-CSF). The virus-like particles display the native gp160 form of the HIV-1 Envelope glycoprotein (Env) and are designed to elicit antibody against the natural form of Env on virus and virus-infected cells. The DNA-expressed HIV Gag, Pol and Env proteins also have the potential to elicit virus-specific CD4 and CD8 T cells. The purpose of the co-expressed GM-CSF is to target a cytokine that recruits, expands and differentiates macrophages and dendritic cells to the site of VLP expression. The GEO-D03 DNA vaccine is currently entered into human trials as a prime for a recombinant modified vaccinia Ankara (MVA) boost. In preclinical studies in macaques using an SIV prototype vaccine, this vaccination regimen elicited both anti-viral T cells and antibody, and provided 70% protection against acquisition during 12 weekly rectal exposures with a heterologous SIV. Higher avidity of the Env-specific Ab for the native form of the Env in the challenge virus correlated with lower likelihood of SIV infection. PMID:23111169

  11. Fever of unknown origin: prospective comparison of diagnostic value of 18F-FDG PET and 111In-granulocyte scintigraphy

    DEFF Research Database (Denmark)

    Kjaer, Andreas; Lebech, Anne-Mette; Eigtved, Annika

    2004-01-01

    The diagnostic work-up in patients with fever of unknown origin (FUO) is often challenging and frequently includes nuclear medicine procedures. Whereas a role for leucocyte or granulocyte scintigraphy in FUO is generally accepted, a possible role of fluorine-18 fluorodeoxyglucose (FDG) positron...... emission tomography (PET) in these patients remains to be established. To study this, we compared prospectively, on a head-to-head basis, the diagnostic value of FDG-PET and indium-111 granulocyte scintigraphy in patients with FUO. Nineteen patients with FUO underwent both FDG-PET and (111)In......-granulocyte scintigraphy within 1 week. FDG-PET scans and granulocyte scintigrams were reviewed by different doctors who were blinded to the result of the other investigation. The diagnostic values of FDG-PET and granulocyte scintigraphy were evaluated with regard to identification of a focal infectious...

  12. Aloantígenos de granulocitos: Importancia clínica The granulocyte alloantigens. Clinical importance

    Directory of Open Access Journals (Sweden)

    María del Rosario López De Roux

    2003-12-01

    Full Text Available Los aloantígenos de granulocitos se agrupan en 2 grandes categorías: antígenos específicos de granulocitos y antígenos cuya distribución es más amplia y comprende otras líneas celulares. En 1998 se acordó establecer una nueva nomenclatura de los aloantígenos de granulocitos, basada en la localización glucoproteica de estos antígenos. La molécula FcgRIIIb es un miembro de la superfamilia de inmunoglobulinas (CD 16 en la cual se asientan varios de los aloantígenos específicos de granulocitos. Existen otros aloantígenos cuya función y localización se desconocen. Estas moléculas son de gran importancia clínica, pues se ven envueltas en una serie de enfermedades como la neutropenia neonatal aloinmune, cuyo carácter clínico moderado hace que pase inadvertida, la reacción febril no hemolítica, el daño pulmonar agudo relacionado con la transfusión, la neutropenia inmune asociada con el trasplante de médula ósea y la neutropenia autoinmune. Aunque se han producido avances en la caracterización de los aloantígenos de granulocitos, muchos puntos quedan sin aclarar, entre ellos, la significación clínica de muchos antígenos. El desarrollo creciente de técnicas moleculares, bioquímicas y serológicas para el estudio de los antígenos de células sanguíneas, nos permitirá aclarar los puntos que aún permanecen oscuros en este campo de la investigaciónThe granulocyte alloantigens are grouped into 2 big categories: specific granulocyte antigens and antigens, whose distribution is wider and comprises other cellular lines. In 1998, it was agreed to establish a new nomenclature of granulocyte alloantigens based on the glycoprotein localization of these antigens. The FcgRIIIb molecule is a member of the superfamily of immunoglobulins (CD 16, in which many of the specific granulocyte alloantigens are found. There are other alloantigens with an unknown function and localization. These molecules have a great clinical importance

  13. Aggressive cutaneous vasculitis in a patient with chronic lymphatic leukemia following granulocyte colony stimulating factor injection: a case report

    Directory of Open Access Journals (Sweden)

    El Husseiny Noha M

    2011-03-01

    Full Text Available Abstract Introduction Vasculitis has been reported in a few cases of chronic lymphatic leukemia and with granulocytic colony-stimulating factor therapy. Those with granulocytic colony-stimulating factor occurred after prolonged therapy and there was a rise in total leukocyte count unlike that in our patient who received just a single injection for the first time. Case presentation We report the case of a 64-year-old Egyptian man with chronic lymphatic leukemia who developed progressive cutaneous vasculitic lesions following injection of a single dose of a granulocytic colony stimulating factor before a third cycle of chemotherapy to improve neutropenia. This is an unusual case and the pathogenesis is not fully understood. Our patient was not on any medical treatment except for bisoprolol for ischemic heart disease. Although aggressive management with steroids, anticoagulation and plasmapheresis had been carried out, the condition was aggressive and the patient's consciousness deteriorated. A magnetic resonance imaging scan of his brain revealed multiple ischemic foci that could be attributed to vasculitis of the brain. Conclusion The aim of this case report is to highlight the importance of monitoring patients on granulocytic colony-stimulating factor therapy, especially in the context of other conditions (such as a hematological malignancy that may lead to an adverse outcome.

  14. CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Doorduijn, JK; van der Holt, B; van Imhoff, GW; van der Hem, KG; Kramer, MHH; van Oers, MHJ; Ossenkoppele, GJ; Verdonck, LF; Verhoef, GEG; Steijaert, MMC; Buijt, I.; Uyl-de Groot, CA; van Agthoven, M; Mulder, AH; Sonneveld, P; Schaafsma, M.

    2003-01-01

    Purpose : To investigate whether the relative close-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma

  15. CHOP compared with CHOP plus granulocyte colony-stimulating factor in elderly patients with aggressive non-Hodgkin's lymphoma

    NARCIS (Netherlands)

    Doorduijn, J. K.; van der Holt, B.; van Imhoff, G. W.; van der Hem, K. G.; Kramer, M. H. H.; van Oers, M. H. J.; Ossenkoppele, G. J.; Schaafsma, M. R.; Verdonck, L. F.; Verhoef, G. E. G.; Steijaert, M. M. C.; Buijt, I.; Uyl-de Groot, C. A.; van Agthoven, M.; Mulder, A. H.; Sonneveld, P.

    2003-01-01

    PURPOSE: To investigate whether the relative dose-intensity of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) chemotherapy could be improved by prophylactic administration of granulocyte colony-stimulating factor (G-CSF) in elderly patients with aggressive non-Hodgkin's lymphoma

  16. Recombinant human granulocyte colony-stimulating factor (rhG-CSF; filgrastim) treatment of clozapine-induced agranulocytosis

    DEFF Research Database (Denmark)

    Nielsen, H

    1993-01-01

    After 10 weeks of treatment with clozapine, severe agranulocytosis was diagnosed in a 33-year-old female. The patient was treated with filgrastim (granulocyte colony-stimulating factor [G-CSF]) 5 micrograms kg-1 day-1. The neutrophil count was 0.234 x 10(9) l-1 on admission, with a further decrease...

  17. Long-chain PUFA in Granulocytes, Mononuclear Cells, and RBC in Patients With Cystic Fibrosis: Relation to Liver Disease

    DEFF Research Database (Denmark)

    Jorgensen, Marianne H.; Ott, Peter; Michaelsen, Kim F.

    2012-01-01

    -related liver disease were matched with 20 CF patients without. Blood samples were analysed for liver biochemistry and haematology. Granulocytes, mononuclear cells, and RBC were separated by density gradient centrifugation, and fatty acid composition was measured by gas chromatography. Hepatic ultrasound...

  18. Stem cell mobilization by granulocyte colony-stimulating factor for myocardial recovery after acute myocardial infarction: a meta-analysis

    DEFF Research Database (Denmark)

    Zohlnhofer, D.; Dibra, A.; Koppara, T.

    2008-01-01

    OBJECTIVES: The objective of this meta-analysis was to evaluate the effect of stem cell mobilization by granulocyte colony-stimulating factor (G-CSF) on myocardial regeneration on the basis of a synthesis of the data generated by randomized, controlled clinical trials of G-CSF after acute...

  19. Increased production of granulocyte-macrophage colony-stimulating factor in Crohn's disease--a possible target for infliximab treatment

    DEFF Research Database (Denmark)

    Agnholt, Jørgen; Kelsen, Jens; Brandsborg, Birgitte

    2004-01-01

    The presence of neutrophils among epithelial cells is one of the major features of the inflammation in Crohn's disease, and has been used to indicate disease activity. The survival of neutrophils outside the blood vessels is limited and their longevity is influenced by granulocyte-macrophage colo...

  20. Staphylococcal enterotoxin A regulates bone marrow granulocyte trafficking during pulmonary inflammatory disease in mice

    Energy Technology Data Exchange (ETDEWEB)

    Takeshita, W.M.; Gushiken, V.O.; Ferreira-Duarte, A.P.; Pinheiro-Torres, A.S.; Roncalho-Buck, I.A. [Department of Biology and Physiology, Faculty of Medicine of Jundiai (FMJ), Jundiai, SP (Brazil); Squebola-Cola, D.M.; Mello, G.C.; Anhê, G.F.; Antunes, E. [Department of Pharmacology, Faculty of Medical Sciences, University of Campinas (UNICAMP), Campinas, SP (Brazil); DeSouza, I.A., E-mail: ivanidesouza@uol.com.br [Department of Biology and Physiology, Faculty of Medicine of Jundiai (FMJ), Jundiai, SP (Brazil)

    2015-09-15

    Pulmonary neutrophil infiltration produced by Staphylococcal enterotoxin A (SEA) airway exposure is accompanied by marked granulocyte accumulation in bone marrow (BM). Therefore, the aim of this study was to investigate the mechanisms of BM cell accumulation, and trafficking to circulating blood and lung tissue after SEA airway exposure. Male BALB/C mice were intranasally exposed to SEA (1 μg), and at 4, 12 and 24 h thereafter, BM, circulating blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected. Adhesion of BM granulocytes and flow cytometry for MAC-1, LFA1-α and VLA-4 and cytokine and/or chemokine levels were assayed after SEA-airway exposure. Prior exposure to SEA promoted a marked PMN influx to BAL and lung tissue, which was accompanied by increased counts of immature and/or mature neutrophils and eosinophils in BM, along with blood neutrophilia. Airway exposure to SEA enhanced BM neutrophil MAC-1 expression, and adhesion to VCAM-1 and/or ICAM-1-coated plates. Elevated levels of GM-CSF, G-CSF, INF-γ, TNF-α, KC/CXCL-1 and SDF-1α were detected in BM after SEA exposure. SEA exposure increased production of eosinopoietic cytokines (eotaxin and IL-5) and BM eosinophil VLA-4 expression, but it failed to affect eosinophil adhesion to VCAM-1 and ICAM-1. In conclusion, BM neutrophil accumulation after SEA exposure takes place by integrated action of cytokines and/or chemokines, enhancing the adhesive responses of BM neutrophils and its trafficking to lung tissues, leading to acute lung injury. BM eosinophil accumulation in SEA-induced acute lung injury may occur via increased eosinopoietic cytokines and VLA-4 expression. - Highlights: • Airway exposure to SEA causes acute lung inflammation. • SEA induces accumulation of bone marrow (BM) in immature and mature neutrophils. • SEA increases BM granulocyte or BM PMN adhesion to ICAM-1 and VCAM-1, and MAC-1 expression. • SEA induces BM elevations of CXCL-1, INF-γ, TNF-α, GM-CSF, G-CSF and

  1. Staphylococcal enterotoxin A regulates bone marrow granulocyte trafficking during pulmonary inflammatory disease in mice

    International Nuclear Information System (INIS)

    Takeshita, W.M.; Gushiken, V.O.; Ferreira-Duarte, A.P.; Pinheiro-Torres, A.S.; Roncalho-Buck, I.A.; Squebola-Cola, D.M.; Mello, G.C.; Anhê, G.F.; Antunes, E.; DeSouza, I.A.

    2015-01-01

    Pulmonary neutrophil infiltration produced by Staphylococcal enterotoxin A (SEA) airway exposure is accompanied by marked granulocyte accumulation in bone marrow (BM). Therefore, the aim of this study was to investigate the mechanisms of BM cell accumulation, and trafficking to circulating blood and lung tissue after SEA airway exposure. Male BALB/C mice were intranasally exposed to SEA (1 μg), and at 4, 12 and 24 h thereafter, BM, circulating blood, bronchoalveolar lavage (BAL) fluid and lung tissue were collected. Adhesion of BM granulocytes and flow cytometry for MAC-1, LFA1-α and VLA-4 and cytokine and/or chemokine levels were assayed after SEA-airway exposure. Prior exposure to SEA promoted a marked PMN influx to BAL and lung tissue, which was accompanied by increased counts of immature and/or mature neutrophils and eosinophils in BM, along with blood neutrophilia. Airway exposure to SEA enhanced BM neutrophil MAC-1 expression, and adhesion to VCAM-1 and/or ICAM-1-coated plates. Elevated levels of GM-CSF, G-CSF, INF-γ, TNF-α, KC/CXCL-1 and SDF-1α were detected in BM after SEA exposure. SEA exposure increased production of eosinopoietic cytokines (eotaxin and IL-5) and BM eosinophil VLA-4 expression, but it failed to affect eosinophil adhesion to VCAM-1 and ICAM-1. In conclusion, BM neutrophil accumulation after SEA exposure takes place by integrated action of cytokines and/or chemokines, enhancing the adhesive responses of BM neutrophils and its trafficking to lung tissues, leading to acute lung injury. BM eosinophil accumulation in SEA-induced acute lung injury may occur via increased eosinopoietic cytokines and VLA-4 expression. - Highlights: • Airway exposure to SEA causes acute lung inflammation. • SEA induces accumulation of bone marrow (BM) in immature and mature neutrophils. • SEA increases BM granulocyte or BM PMN adhesion to ICAM-1 and VCAM-1, and MAC-1 expression. • SEA induces BM elevations of CXCL-1, INF-γ, TNF-α, GM-CSF, G-CSF and

  2. Seroprevalence and risk factors associated with Ehrlichia canis, Anaplasma spp., Borrelia burgdorferi sensu lato, and D. immitis in hunting dogs from southern Italy.

    Science.gov (United States)

    Piantedosi, Diego; Neola, Benedetto; D'Alessio, Nicola; Di Prisco, Francesca; Santoro, Mario; Pacifico, Laura; Sgroi, Giovanni; Auletta, Luigi; Buch, Jesse; Chandrashekar, Ramaswamy; Breitschwerdt, Edward B; Veneziano, Vincenzo

    2017-10-01

    Canine vector-borne diseases (CVBDs) are caused by a range of pathogens transmitted to dogs by arthropods. The present study investigates Ehrlichia canis, Anaplasma spp., Borrelia burgdorferi sensu lato, and Dirofilaria immitis seroprevalences in hunting dogs from southern Italy. Dogs (no. 1335) were tested using a commercial in-clinic enzyme-linked immunosorbent assay kit. Odds ratios (ORs) were calculated by logistic regression analysis to identify risk factors. Overall, 138/1335 dogs (10.3%) were seroreactive to at least one CVBD pathogen. E. canis, Anaplasma spp., B. burgdorferi s.l., and D. immitis seroprevalences were 7.6, 4.4, 0.3, and 0.2%, respectively. E. canis and Anaplasma spp. co-exposures were found in 30 dogs (2.2%), compared with Anaplasma spp. and B. burgdorferi s.l. co-exposures in 2 dogs (0.1%). Adult age was a risk factor for E. canis (OR 2.35) seroreactivity whereas hunting fur-bearing animals for E. canis (OR 4.75) and Anaplasma spp. (OR 1.87), respectively. The historical presence of tick infestation was identified as a risk factor for positivity to E. canis (OR 2.08) and Anaplasma spp. (OR 2.15). Finally, larger dog pack size was significantly associated with E. canis (OR 1.85) and Anaplasma spp. (OR 2.42) exposures. The results of the present survey indicated that hunting dog populations are at relative risk of CVBDs in southern Italy. Further studies are needed to evaluate the role of hunting dogs in the epidemiology of vector-borne organisms due to sharing common environments with wild, sympatric animal populations.

  3. Aliphatic alcohols of illegally produced spirits can act synergistically on superoxide-anion production by human granulocytes.

    Science.gov (United States)

    Arnyas, Ervin M; Pál, László; Kovács, Csilla; Adány, Róza; McKee, Martin; Szűcs, Sándor

    2012-10-01

    Aliphatic alcohols present in illegally produced spirits in a large number of low and middle income countries have been implicated in the etiology of chronic liver disease and cirrhosis. Previous studies have confirmed that chronic alcoholism can lead to increased susceptibility to infectious diseases. Reduced superoxide-anion (O(2)·(-)) production by granulocytes could provide a mechanism by which antimicrobial defense is impaired in alcoholics. In vitro experiments have also demonstrated that ethanol can inhibit granulocyte O(2)·(-) generation. Aliphatic alcohols consumed as contaminants of illicit spirits may also influence O(2)·(-) production thereby contributing to a decrease in microbicidal activity. The aim of this study was to investigate this possibility. It measured the O(2)·(-) production by human granulocytes following treatment of the cells with aliphatic alcohol contaminants found in illicit spirits. Granulocytes were isolated from human buffy coats with centrifugal elutriation and then treated with individual aliphatic alcohols and their mixture. The O(2)·(-) production was stimulated with phorbol-12-13-dibutyrate and N-formyl-methionyl-leucyl-phenylalanine (FMLP) and measured by superoxide dismutase inhibitable reduction of ferricytochrome c. Aliphatic alcohols of illegally produced spirits inhibited the FMLP-induced O(2)·(-) production in a concentration dependent manner. They suppressed O(2)·(-) generation at 2.5-40 times lower concentrations when combined than when tested individually. Aliphatic alcohols found in illegally produced spirits can inhibit FMLP-induced O(2)·(-) production by granulocytes in a concentration-dependent manner. Due to their synergistic effects, it is possible that, in combination with ethanol, they may inhibit O(2)·(-) formation in heavy episodic drinkers.

  4. Granulocytic sarcoma masquerading as Ewing′s sarcoma: A diagnostic dilemma

    Directory of Open Access Journals (Sweden)

    Haresh Kunhi

    2008-01-01

    Full Text Available An eleven-year-old boy presented with a swelling in his left elbow. Radiologically the features were that of an Ewing′s sarcoma involving the ulna. Histopathology showed small round cell tumor strongly positive for Monoclonal Imperial Cancer research fund 2 (MIC2 antigen. Similar cells in the bone marrow were involved with MIC2 positivity. The patient developed skin lesions, which on biopsy were found to be chloromas. The initial biopsies were reevaluated with special stains revealing granulocytic sarcomas in acute myeloid leukemia masquerading as Ewing′s due to its MIC2 positivity. The possibility of myeloid neoplasms should be considered routinely with known MIC2 positive round cell tumors.

  5. Acute antibody-mediated rejection of skin grafts without involvement of granulocytes or complement

    International Nuclear Information System (INIS)

    Bogman, M.J.; Cornelissen, I.M.; Koene, R.A.

    1984-01-01

    In immunosuppressed mice that carry rat skin xeno-grafts, acute antibody-mediated graft rejection (AAR) can be induced by intravenous administration of mouse anti-rat globulin. Dependent on the amount of antibody injected and on the complement status of the recipient, an Arthus-like or a Shwartzman-like pattern of vasculitis occurs. The role of polymorphonuclear granulocytes (PMNs) in either type of vasculitis was tested by inducing AAR in recipients depleted of PMNs by total body irradiation. Despite the absence of PMNs in the graft vessels, AAR occurred both in the Arthus-like and in the Shwartzman-like type. Moreover, AAR could be elicited in PMN-depleted recipients that were complement-depleted by cobra venom factor treatment or were congenitally C5-deficient. We conclude that neither the PMN nor complement is an essential mediator the PMN nor complement is an essential mediator in this form of antibody-mediated vasculitis

  6. Structural insights into the backbone-circularized granulocyte colony-stimulating factor containing a short connector.

    Science.gov (United States)

    Miyafusa, Takamitsu; Shibuya, Risa; Honda, Shinya

    2018-06-02

    Backbone circularization is a powerful approach for enhancing the structural stability of polypeptides. Herein, we present the crystal structure of the circularized variant of the granulocyte colony-stimulating factor (G-CSF) in which the terminal helical region was circularized using a short, two-amino acid connector. The structure revealed that the N- and C-termini were indeed connected by a peptide bond. The local structure of the C-terminal region transited from an α helix to 3 10 helix with a bend close to the N-terminal region, indicating that the structural change offset the insufficient length of the connector. This is the first-ever report of a crystal structure of the backbone of a circularized protein. It will facilitate the development of backbone circularization methodology. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Bone and bone-marrow blood flow in chronic granulocytic leukemia and primary myelofibrosis

    International Nuclear Information System (INIS)

    Lahtinen, R.; Lahtinen, T.; Romppanen, T.

    1982-01-01

    Blood flow in hematopoietic bone marrow and in nonhematopoietic bone has been measured with a Xe-133 washout method in 20 patients with chronic granulocytic leukemia (CGL) and in seven with primary myelofibrosis. Age-matched healthy persons served as controls. Bone-marrow blood flow in CGL was dependent upon the phase of the disease. In the metamorphosis phase, bone-marrow blood flow was high compared with that in the well-controlled phase. Apart from the initial phase, the mean values for bone blood flow in CGL were increased compared with the values of the healthy controls. In myelofibrosis the bone blood flow was also increased. Bone-marrow blood flow in these diseases was dependent upon the cellularity of bone marrow as measured morphometrically

  8. Aleukemic granulocytic sarcoma presenting at multiple sites: ovary, breast and soft tissue

    Directory of Open Access Journals (Sweden)

    Jitendra Singh Nigam

    2012-06-01

    Full Text Available An 18 year old female presented with the history of pain in abdomen, breast engorgement, swelling over both legs and breathlessness for three month. On clinical examination diagnosis of fibroadenoma breast was made. Ultrasonography of abdomen showed bilateral ovarian mass. Bilateral salpingo-ophrectomy was done and specimen was sent for histological examination. Two lobulated solid masses of tissues the larger one measuring 13x8x5 cm and smaller one measuring 10x7x5 cm in size received. Microscopic examination showed monomorphic population of discohesive, hyperchromatic small round cells had high N:C ratio, coarse chromatin, conspicuous nucleoli and scant to moderate amount of basophilic cytoplasm, lying in sheets and separated by fibrous strands and diffusely infiltrating the ovarian stroma. Fine needle aspiration from breast lump and leg swelling showed predominant population of blast cells. Myeloperoxidase was strongly positive and diagnosis of granulocytic sarcoma was confirmed.

  9. Promotion of Tumor Invasion by Cooperation of Granulocytes and Macrophages Activated by Anti-tumor Antibodies

    Directory of Open Access Journals (Sweden)

    Emilio Barbera-Guillem

    1999-11-01

    Full Text Available We investigated the potential role of anti-tumor antibodies and tumor antigens in the formation of immune complexes which promote matrix degradation and angiogenesis. B-cell deficient or B-cell depleted mice showed a reduction in tumor invasion and metastasis. In vitro invasion assays and in vivo models of metastasis showed that anti-sTn antibodies and sTn tumor antigens form complexes which induce granulocytes and macrophages together to mediate tumor invasion and metastasis by processes including extracellular matrix degradation and angiogenesis. These results suggest the existence of a tumor promoting role of a B-cell immune response induced by shed tumor associated antigens of solid, nonlymphoid tumors.

  10. Radiation-induced enlargement of granulocytic and macrophage progenitor cells in mouse bone marrow

    Energy Technology Data Exchange (ETDEWEB)

    Metcalf, D; Johnson, G R; Wilson, J [Walter and Eliza Hall Inst. of Medical Research, Parkville (Australia)

    1977-01-01

    The peak sedimentation velocity of C/sub 57/BL mouse bone marrow progenitors of granulocytes and macrophages (GM-colony-forming cells, GM-CFC's) increased from 4.3 mm/h to 7 to 8 mm/h by 2 days after 250 rad whole body irradiation and slowly returned to normal over the next 3 weeks. Preliminary irradiation and/or endotoxin injection did not prevent this radiation-induced change. Some change in sedimentation velocity was seen with as little as 100 rad irradiation. Neither buoyant density nor cell cycle changes could account for the sedimentation velocity data which therefore indicate a major volume increase in the GM-CFC's. This size enlargement affected all subpopulations of GM-CFC's which consequently maintained their size relationship with one another.

  11. Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation

    Energy Technology Data Exchange (ETDEWEB)

    Doney, K; Buckner, C D; Sale, G E; Ramberg, R; Boyd, C; Thomas, E D [Fred Hutchinson Cancer Research Institute; Washington Univ., Seattle (USA). School of Medicine)

    1978-01-01

    Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients reveived a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with succesful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration.

  12. Granulocyte Colony-Stimulating Factor in the Treatment of Acute Radiation Syndrome: A Concise Review

    Directory of Open Access Journals (Sweden)

    Michal Hofer

    2014-04-01

    Full Text Available This article concisely summarizes data on the action of one of the principal and best known growth factors, the granulocyte colony-stimulating factor (G-CSF, in a mammalian organism exposed to radiation doses inducing acute radiation syndrome. Highlighted are the topics of its real or anticipated use in radiation accident victims, the timing of its administration, the possibilities of combining G-CSF with other drugs, the ability of other agents to stimulate endogenous G-CSF production, as well as of the capability of this growth factor to ameliorate not only the bone marrow radiation syndrome but also the gastrointestinal radiation syndrome. G-CSF is one of the pivotal drugs in the treatment of radiation accident victims and its employment in this indication can be expected to remain or even grow in the future.

  13. Treatment of chronic granulocytic leukemia by chemotherapy, total body irradiation and allogeneic bone marrow transplantation

    International Nuclear Information System (INIS)

    Doney, K.; Buckner, C.D.; Sale, G.E.; Ramberg, R.; Boyd, C.; Thomas, E.D.; Washington Univ., Seattle

    1978-01-01

    Fourteen patients with chronic granulocytic leukemia received bone marrow grafts from HLA identical siblings. Ten patients were in blast crisis prior to grafting, three were in an accelerated phase of their disease, and one was aplastic secondary to chemotherapy. Prior to transplant all patients were conditioned with chemotherapy including cyclophosphamide plus 1,000 rad of total body irradiation. Ten patients achieved engraftment while four died 1 to 26 days after marrow infusion without functioning grafts. Two patients reveived a second infusion of donor marrow because of delayed engraftment. Neither marrow cell dose nor presence of myelofibrosis correlated with succesful engraftment. Three out of ten engrafted patients developed graft-versus-host disease. Interstitial pneumonia occurred in seven patients. The immediate cause of death was bacterial septicemia in six patients. All evidence of leukemia disappeared in nine out of ten evaluable patients. The median survival was 43 days. One patient had a complete remission of 16 months duration. (Author)

  14. Factor H C-Terminal Domains Are Critical for Regulation of Platelet/Granulocyte Aggregate Formation

    Directory of Open Access Journals (Sweden)

    Adam Z. Blatt

    2017-11-01

    Full Text Available Platelet/granulocyte aggregates (PGAs increase thromboinflammation in the vasculature, and PGA formation is tightly controlled by the complement alternative pathway (AP negative regulator, Factor H (FH. Mutations in FH are associated with the prothrombotic disease atypical hemolytic uremic syndrome (aHUS, yet it is unknown whether increased PGA formation contributes to the thrombosis seen in patients with aHUS. Here, flow cytometry assays were used to evaluate the effects of aHUS-related mutations on FH regulation of PGA formation and characterize the mechanism. Utilizing recombinant fragments of FH spanning the entire length of the protein, we mapped the regions of FH most critical for limiting AP activity on the surface of isolated human platelets and neutrophils, as well as the regions most critical for regulating PGA formation in human whole blood stimulated with thrombin receptor-activating peptide (TRAP. FH domains 19–20 were the most critical for limiting AP activity on platelets, neutrophils, and at the platelet/granulocyte interface. The role of FH in PGA formation was attributed to its ability to regulate AP-mediated C5a generation. AHUS-related mutations in domains 19–20 caused differential effects on control of PGA formation and AP activity on platelets and neutrophils. Our data indicate FH C-terminal domains are key for regulating PGA formation, thus increased FH protection may have a beneficial impact on diseases characterized by increased PGA formation, such as cardiovascular disease. Additionally, aHUS-related mutations in domains 19–20 have varying effects on control of TRAP-mediated PGA formation, suggesting that some, but not all, aHUS-related mutations may cause increased PGA formation that contributes to excessive thrombosis in patients with aHUS.

  15. Highly Expressed Granulocyte Colony-Stimulating Factor (G-CSF) and Granulocyte Colony-Stimulating Factor Receptor (G-CSFR) in Human Gastric Cancer Leads to Poor Survival.

    Science.gov (United States)

    Fan, Zhisong; Li, Yong; Zhao, Qun; Fan, Liqiao; Tan, Bibo; Zuo, Jing; Hua, Kelei; Ji, Qiang

    2018-03-23

    BACKGROUND Chemotherapy for advanced gastric cancer (GC) patients has been the mainstay of therapy for many years. Although adding anti-angiogenic drugs to chemotherapy improves patient survival slightly, identifying anti-angiogenic therapy-sensitive patients remains challenging for oncologists. Granulocyte colony-stimulating factor (G-CSF) promotes tumor growth and angiogenesis, which can be minimized with the anti-G-CSF antibody. Thus, G-CSF might be a potential tumor marker. However, the effects of G-CSF and G-CSFR expression on GC patient survival remain unclear. MATERIAL AND METHODS Seventy GC tissue samples were collected for G-CSF and G-CSFR detection by immunohistochemistry. A total of 40 paired GC tissues and matched adjacent mucosa were used to measure the G-CSF and G-CSFR levels by ELISA. Correlations between G-CSF/G-CSFR and clinical characteristics, VEGF-A levels and overall survival were analyzed. Biological function and underlying mechanistic investigations were carried out using SGC7901 cell lines, and the effects of G-CSF on tumor proliferation, migration, and tube formation were examined. RESULTS The levels of G-CSFR were upregulated in GC tissues compared to normal mucosa tissues. Higher G-CSF expression was associated with later tumor stages and higher tumor VEGF-A and serum CA724 levels, whereas higher G-CSFR expression was associated with lymph node metastasis. Patients with higher G-CSF expression had shorter overall survival times. In vitro, G-CSF stimulated SGC7901 proliferation and migration through the JAK2/STAT3 pathway and accelerated HUVEC tube formation. CONCLUSIONS These data suggest that increased G-CSF and G-CSFR in tumors leads to unfavorable outcomes for GC patients by stimulating tumor proliferation, migration, and angiogenesis, indicating that these factors are potential tumor targets for cancer treatment.

  16. Disease: H01142 [KEGG MEDICUS

    Lifescience Database Archive (English)

    Full Text Available H01142 Ehrlichia ewingii infection Human ehrlichiosis is a recently recognized tic...k-borne infection. Ehrlichia ewingii has been identified as a cause of human disease in addition to formerly... known pathogenic Ehrlichia species. Infectious disease ... Ehrlichia ewingii ... 16S rRNA [KO:K01977] ... Other dis... Manian FA, Liddell AM, Schmulewitz N, Storch GA ... TITLE ... Ehrlichia ewingii, a

  17. Mouse infection models for space flight immunology

    Science.gov (United States)

    Chapes, Stephen Keith; Ganta, Roman Reddy; Chapers, S. K. (Principal Investigator)

    2005-01-01

    Several immunological processes can be affected by space flight. However, there is little evidence to suggest that flight-induced immunological deficits lead to illness. Therefore, one of our goals has been to define models to examine host resistance during space flight. Our working hypothesis is that space flight crews will come from a heterogeneous population; the immune response gene make-up will be quite varied. It is unknown how much the immune response gene variation contributes to the potential threat from infectious organisms, allergic responses or other long term health problems (e.g. cancer). This article details recent efforts of the Kansas State University gravitational immunology group to assess how population heterogeneity impacts host health, either in laboratory experimental situations and/or using the skeletal unloading model of space-flight stress. This paper details our use of several mouse strains with several different genotypes. In particular, mice with varying MHCII allotypes and mice on the C57BL background with different genetic defects have been particularly useful tools with which to study infections by Staphylococcus aureus, Salmonella typhimurium, Pasteurella pneumotropica and Ehrlichia chaffeensis. We propose that some of these experimental challenge models will be useful to assess the effects of space flight on host resistance to infection.

  18. Petiveria alliacea L. extract protects mice against Listeria monocytogenes infection--effects on bone marrow progenitor cells.

    Science.gov (United States)

    Quadros, M R; Souza Brito, A R; Queiroz, M L

    1999-02-01

    In this study we have investigated the effects of Petiveria alliacea on the hematopoietic response of mice infected with Listeria monocytogenes. Our results demonstrate a protective effect of the crude extract of P. alliacea since the survival of the treated/infected was higher than that in the infected group. Moreover, the number of granulocyte/macrophage colonies (CFU-GM) and the serum colony stimulating activity levels were increased in the treated/infected mice in relation to the infected group. These results suggest an immunomodulation of Petiveria alliacea extract on hematopoiesis, which may be responsible, at least in part, for the increased resistance of mice to Listeria monocytogenes infection.

  19. Hematological remission and long term hematological control of acute myeloblastic leukemia induced and maintained by granulocyte-colony stimulating factor (G-CSF) therapy.

    Science.gov (United States)

    Xavier, Luciana; Cunha, Manuel; Gonçalves, Cristina; Teixeira, Maria dos Anjos; Coutinho, Jorge; Ribeiro, António Carlos Pinto; Lima, Margarida

    2003-12-01

    We describe a case of a patient with CD34+, TdT+, CD13-, CD33-, MPO- undifferentiated acute leukemia who refused chemotherapy and who achieved complete hematological remission 14 months after the diagnosis, during a short course of granulocyte-colony stimulating factor (G-CSF) for neutropenia and life threatening infection. Relapse occurred approximately one year later and G-CSF was reintroduced, being maintained for 4 months, at a dose and frequency adapted to maintain normal blood counts, a complete hematological remission being achieved again. Five months after withdrawing the G-CSF therapy a second relapse was observed; G-CSF was tried again with success, resulting in a very good hematological response that was sustained by G-CSF maintenance therapy. One year latter there was the need of increasing the doses of G-CSF in order to obtain the same hematological effect, at same time blast cells acquired a more mature CD34+, TdT-, CD13+, CD33-, MPO+ myeloid phenotype. Finally, the patient developed progressive neutropenia, anemia, thrombocytopenia and acute leukemia in spite of G-CSF therapy, dying 64 months after initial diagnosis (50 months after starting G-CSF therapy) with overt G-CSF resistant acute myeloblastic leukemia (AML), after failure of conventional induction chemotherapy.

  20. Changes in adhesion molecule expression and oxidative burst activity of granulocytes and monocytes during open-heart surgery with cardiopulmonary bypass compared with abdominal surgery

    DEFF Research Database (Denmark)

    Toft, P; Nielsen, C H; Tønnesen, Else Kirstine

    1998-01-01

    Cardiac and major abdominal surgery are associated with granulocytosis in peripheral blood. The purpose of the present study was to describe the granulocyte and monocyte oxidative burst and the expression of adhesion molecules following cardiac surgery with cardiopulmonary bypass and abdominal...... during cardiopulmonary bypass was observed. The percentage of CD11a-positive granulocytes increased from 30% pre-operatively to 75% following cardiopulmonary bypass, while CD44-positive granulocytes increased from 5% to 13%. Despite the extent of the changes, these were not significant. The oxidative...... to an increased per-operative oxidative burst activity, and the induction of adhesion molecules on granulocytes associated with the cardiopulmonary bypass and surgery. In conclusion, open-heart surgery with cardiopulmonary bypass was associated with a rapid and pronounced activation of leukocytes which may play...

  1. [The effect of lithium carbonate on the leukocyte count following ionizing radiation. 4. The effect of lithium carbonate on the activation of granulocytes].

    Science.gov (United States)

    Wolf, G; Müller, G M; Kehrberg, G

    1989-01-01

    From numerous investigations it is known that lithium carbonate promotes granulocytopoiesis by stimulation of CSF (colony stimulating factor) in bone marrow. To prove if no immature, in their functions restricted cells are delivered from bone marrow, the activity of granulocytes was tested in vitro in patients with lithium therapy. It could be seen that granulocytes of peripheral blood show an increased in-vitro-activation after lithium influence in vivo.

  2. Timing of granulocyte-colony stimulating factor treatment after acute myocardial infarction and recovery of left ventricular function: results from the STEMMI trial

    DEFF Research Database (Denmark)

    Overgaard, Mikkel; Ripa, Rasmus Sejersten; Wang, Yongzhong

    2010-01-01

    Granulocyte-colony stimulating factor (G-CSF) therapy after ST-elevation myocardial infarction (STEMI) have not demonstrated impact on systolic recovery compared to placebo. However, recent studies suggest that timing of G-CSF therapy is crucial.......Granulocyte-colony stimulating factor (G-CSF) therapy after ST-elevation myocardial infarction (STEMI) have not demonstrated impact on systolic recovery compared to placebo. However, recent studies suggest that timing of G-CSF therapy is crucial....

  3. Myeloprotective Action of Combined Application of Ukrainian Recombinant Granulocyte Colony Stimulating Factor (r-GCSF and Enterosorbent С2 in Rats with Malignant Guerin Carcinoma

    Directory of Open Access Journals (Sweden)

    Todor, I.M.

    2015-03-01

    Full Text Available The aim of the study is to analyze myeloprotective effect of novel enterosorbents alone and in combination with two recombinant granulocyte colony stimulating factors: Neupogen (Switzerland and r- GCSF (Ukraine. It is proven that Ukrainian version of recombinant granulocyte colony stimulating factor r-GCSF does not concede officinal drug Neupogen (Switzerland by its experimental therapeutic action and combined use with enterosorbent C2 significantly increases myeloprotective effect of both GCSF versions.

  4. A Randomized Case-Controlled Study of Recombinant Human Granulocyte Colony Stimulating Factor for the Treatment of Sepsis in Preterm Neutropenic Infants

    OpenAIRE

    Aktaş, Doğukan; Demirel, Bilge; Gürsoy, Tuğba; Ovalı, Fahri

    2015-01-01

    To investigate the efficacy and safety of recombinant human granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor (rhG-CSF) to treat sepsis in neutropenic preterm infants. Methods: Fifty-six neutropenic preterm infants with suspected or culture-proven sepsis hospitalized in Zeynep Kamil Maternity and Children's Educational and Training Hospital, Kozyatağı/Istanbul, Turkey between January 2008 and January 2010 were enrolled. Patients were ...

  5. Granulocytic Sarcoma by AML M4eo (inv16 after Allogeneic Stem Cell Transplantation without Bone Marrow Involvement

    Directory of Open Access Journals (Sweden)

    Stephan Zaenker

    2011-01-01

    Full Text Available Granulocytic sarcoma (GS represents a rare type of extramedullar manifestation from the acute myeloid leukaemia (AML. We report the case of a patient with recurrences of AML M4eo leukaemia in the uterus and the small intestine at 3 and 5 years, respectively, after matched related peripheral blood stem cell transplantation (PBSCT. The patient underwent the withdrawal of immunosuppression, hysterectomy, and local irradiation at first relapse, as well as systemic chemotherapy and donor lymphocyte infusions at second recurrence, inducing a second and third complete remission, respectively. At year six after transplantation, the patient experienced disease progression by meningeosis leukaemia to which she succumbed despite intrathecal chemotherapy. Following allogeneic stem cell transplantation, awareness for atypical manifestations of granulocytic sarcoma appears prudent, the cellular immunotherapy should aim at immunological disease control.

  6. Comparision of indium-111 oxinate labelled autologous granulocytes with indium-111 oxinate and indium-111 chloride as abscess scanning agents

    International Nuclear Information System (INIS)

    Goedemans, W.T.; Hardemann, M.R.; Belfer, A.J.

    1980-01-01

    Bacterial abscesses were evoked in goats. Imaging of these abscesses was obtained by means of labelling autologous granulocytes with 111 In oxinate, reinjection of the cells into the animal, and scintigraphy by gamma camera one day later. Comparable imaging results, however, were obtained after intravenous of 111 In oxinate or of 111 In chloride. The gamma camera images were supported by tissue distribution studies. In the case of administration of 111 In oxinate to the goats, the radioactivity accumulated in the cell fraction of the blood to a significant extent. This did not occur in the case of plain 111 In chloride. It remained unexplained why such different accumulation in cells did not result in differences in the scintigraphic studies. Blood clearance studies supplied conclusive evidence that the granulocytes stayed in the circulation for several days following labelling with 111 In oxinate and reinjection of the cells into the animals. (orig.) [de

  7. Granulocyte macrophage-colony-stimulating factor mouthwashes heal oral ulcers during head and neck radiotherapy

    International Nuclear Information System (INIS)

    Rovirosa, Angeles; Ferre, Jorge; Biete, Albert

    1998-01-01

    Purpose: To evaluate the effectiveness of granulocyte macrophage-colony-stimulating factor GM-CSF mouthwashes in the epithelization of radiation-induced oral mucosal ulceration, control of pain, and weight loss. Methods and Materials: Twelve patients received curative radiotherapy for head and neck carcinoma. All had oropharyngeal and/or oral mucosa irradiation, with a median dose of 72 Gy (range 50-74), with conventional fractionation. A total of 300 μg of GM-CSF in 250 cc of water for 1 h of mouthwashing was prescribed. The procedure started once oral ulceration in the irradiation field was detected. Patients, examined twice a week, were evaluated for oral ulceration, pain, and weight loss. Blood tests were taken weekly during GM-CSF administration. A comparison was carried out with 12 retrospective case-matched controls. Results: In the GM-CSF group, mucosa ulcerations healed in 9 of 12 (75%) of the patients during the course of the radiotherapy. Fifty percent of the patients said they felt less pain during the GM-CSF treatment; 30% needed morphine. The mean and median weight loss as a percentage of baseline weight in addition to the actual weight were 4.2% and 3%, respectively (variation ranged between a gain of 1% and a loss of 13%). No GM-CSF-related side effects were found. In the case control group, in the 12 cases, oral ulcerations increased during radiotherapy and two patients needed intubation intake and hospital admission, as opposed to the GM-CSF group. The mean and median percentage of weight loss were 5.8% and 5%, respectively. Sixty percent of patients needed morphine, as opposed to 30% in the GM-CSF group. Conclusions: Granulocyte macrophage-colony-stimulating factor was effective in curing mucosal ulcerations during the course of radiotherapy. This is the first time we have seen a drug with this capacity. Although the GM-CSF seems to be effective in the control of pain, oral intake, and weight loss, we need further studies with a greater number

  8. Granulocyte colony-stimulating factor mobilizes functional endothelial progenitor cells in patients with coronary artery disease.

    Science.gov (United States)

    Powell, Tiffany M; Paul, Jonathan D; Hill, Jonathan M; Thompson, Michael; Benjamin, Moshe; Rodrigo, Maria; McCoy, J Philip; Read, Elizabeth J; Khuu, Hanh M; Leitman, Susan F; Finkel, Toren; Cannon, Richard O

    2005-02-01

    Endothelial progenitor cells (EPCs) that may repair vascular injury are reduced in patients with coronary artery disease (CAD). We reasoned that EPC number and function may be increased by granulocyte colony-stimulating factor (G-CSF) used to mobilize hematopoietic progenitor cells in healthy donors. Sixteen CAD patients had reduced CD34(+)/CD133(+) (0.0224+/-0.0063% versus 0.121+/-0.038% mononuclear cells [MNCs], P<0.01) and CD133(+)/VEGFR-2(+) cells, consistent with EPC phenotype (0.00033+/-0.00015% versus 0.0017+/-0.0006% MNCs, P<0.01), compared with 7 healthy controls. Patients also had fewer clusters of cells in culture, with out-growth consistent with mature endothelial phenotype (2+/-1/well) compared with 16 healthy subjects at high risk (13+/-4/well, P<0.05) or 14 at low risk (22+/-3/well, P<0.001) for CAD. G-CSF 10 microg/kg per day for 5 days increased CD34(+)/CD133(+) cells from 0.5+/-0.2/microL to 59.5+/-10.6/microL and CD133(+)/ VEGFR-2(+) cells from 0.007+/-0.004/microL to 1.9+/-0.6/microL (both P<0.001). Also increased were CD133(+) cells that coexpressed the homing receptor CXCR4 (30.4+/-8.3/microL, P<0.05). Endothelial cell-forming clusters in 10 patients increased to 27+/-9/well after treatment (P<0.05), with a decline to 9+/-4/well at 2 weeks (P=0.06). Despite reduced EPCs compared with healthy controls, patients with CAD respond to G-CSF with increases in EPC number and homing receptor expression in the circulation and endothelial out-growth in culture. Endothelial progenitor cells (EPCs) are reduced in coronary artery disease. Granulocyte colony-stimulating factor (CSF) administered to patients increased: (1) CD133+/VEGFR-2+ cells consistent with EPC phenotype; (2) CD133+ cells coexpressing the chemokine receptor CXCR4, important for homing of EPCs to ischemic tissue; and (3) endothelial cell-forming clusters in culture. Whether EPCs mobilized into the circulation will be useful for the purpose of initiating vascular growth and myocyte repair

  9. Survey of canine tick-borne diseases in Lábrea, Brazilian Amazon: ‘accidental’ findings of Dirofilaria immitis infection

    Directory of Open Access Journals (Sweden)

    Herbert Sousa Soares

    2014-12-01

    Full Text Available Blood samples were collected from 99 domestic dogs from the urban and rural areas of the Lábrea municipality, state of Amazonas, Brazil. Canine serum samples were tested by immunofluorescence assay against Rickettsia spp., which revealed that only 3.0% (1/33 and 7.6% (5/66 of the dogs from urban and rural areas, respectively, reacted positively to at least one Rickettsia species. DNA was extracted from canine blood and tested by a battery of PCR assays targeting protozoa of the genera Babesia and Hepatozoon, and bacteria of the genera Rickettsia and Ehrlichia and family Anaplasmataceae. All samples were negative in the PCR assays targeting the genera Babesia, Hepatozoon, Ehrlichia and Rickettsia. For Anaplasmataceae, 3% (1/33 and 39.4% (26/66 of the urban and rural dogs, respectively, yielded amplicons that generated DNA sequences 100% identical to the corresponding sequence of Wolbachia endosymbiont of Dirofilaria immitis. Because of these results, all canine DNA samples were further tested in a PCR assay targeting filarial nematodes, which was positive for 18.2% (6/33 and 57.6% (38/66 urban and rural dogs, respectively. Filarial-PCR products generated DNA sequences 100% identical to D. immitis. While tick-borne infections were rare in Lábrea, D. immitis infection rates were among the highest reported in South America.

  10. GRANULOCYTE INFILTRATION AND EXPRESSION OF THE PRO-ANGIOGENIC BV8 PROTEIN IN EXPERIMENTAL EL4 AND LEWIS LUNG CARCINOMA TUMORS.

    Science.gov (United States)

    Jiang, Kan; Kwak, Hyeongil; Tosato, Giovanna

    2013-01-18

    Although Vascular Endothelial Growth Factor (VEGF)-targeted therapies have shown efficacy in the treatment of certain advanced cancers, benefits to patients have been modest, which is attributed to tumor resistance to VEGF neutralization. Recent efforts to identify new targets to inhibit tumor angiogenesis have identified Bv8 (prokineticin 2), a myeloid cell-derived protein that promotes endothelial cell growth and tumor angiogenesis, but many mechanistic aspects of the pro-tumorigenic function of Bv8 are unclear. Here we demonstrate that CD11b+, Ly6C+, Ly6G+ granulocytes are the predominant cell source of Bv8 expression in bone marrow, spleen and in tumor tissues. Using granulocyte-deficient Growth factor independence-1 (Gfi1)-null mutant mice and normal littermates, we found that EL4 lymphoma tumors grow significantly larger in the granulocyte and Bv8-deficient mutant mice in comparison to the normal mice that display abundant tumor-associated granulocytes and Bv8 expression. Conversely, Lewis lung carcinoma (LLC-1) tumors grew to a significantly greater size in the normal mice in comparison to the Gfi1-null mice, but normal granulocyte tumor infiltration was modest. Quantitative analysis of tissue vascularization showed that EL4 and LLC-1 tumors from normal and Gfi1-mutant mice are similarly vascularized. These results confirm the critical contribution of the tumor microenvironment in determining the rate of tumor progression independently of tumor angiogenesis, and reveal some of the complexities of granulocyte and Bv8 functions in modulating tumor growth.

  11. Selective Granulocyte and Monocyte Apheresis as a Non-Pharmacological Option for Patients with Inflammatory Bowel Disease

    Science.gov (United States)

    C. Leitner, Gerda; Worel, Nina; Vogelsang, Harald

    2012-01-01

    Ulcerative colitis and Crohn's disease are the two most prevalent inflammatory bowel diseases. In both cases, the medically refractory and steroid-dependent type presents a therapeutic challenge. To help resolve this problem, a mainly Japanese team developed a new therapeutic option. There are two systems, both of which are able to selectively remove the main mediators of the disease, namely the activated pro-inflammatory cytokine-producing granulocytes and monocytes/macrophages, from the patient's blood circulation (GMA = granulocyte monocyte apheresis). One of the two systems is the Adacolumn® (Immunoresearch Laboratories, Takasaki, Japan) consisting of the ADA-monitor and a single-use column, which contains approximately 35,000 cellulose acetate beads. The exact mode of action is not yet sufficiently understood, but however, a modulation of the immune system takes place. As a result, less pro-inflammatory cytokines are released. Furthermore, the production of anti-inflammatory interleukin-1 receptor antagonist is increased, and the apoptosis of granulocytes boosted. The decreased LECAM-1-expression on leukocytes impedes the leukotaxis to the inflamed tissue, and CD10-negative immature granulocytes appear in the peripheral blood. Another effect to be mentioned is the removal of the peripheral dendritic cells and the leachate of regulatory T cells (T-regs). The second system is the Cellsorba® FX Filter (Asahi Medical, Tokyo, Japan). The range of efficiency, the indication, and the procedure are very similar to the Adacolumn. Solely the additional removal of lymphocytes can possibly limit the implementation since lymphopenia can increase the risk of autoimmune disease. Both systems provide a low-risk therapy with few adverse reactions. ASFA recommendations for GMA in inflammatory bowel disease are 2B due to the fact that not enough randomized double-blind studies are available to proof the efficacy of this treatment. PMID:22969694

  12. The chemokine Bv8/prokineticin 2 is up-regulated in inflammatory granulocytes and modulates inflammatory pain

    OpenAIRE

    Giannini, Elisa; Lattanzi, Roberta; Nicotra, Annalisa; Campese, Antonio F.; Grazioli, Paola; Screpanti, Isabella; Balboni, Gianfranco; Salvadori, Severo; Sacerdote, Paola; Negri, Lucia

    2009-01-01

    Neutrophil migration into injured tissues is invariably accompanied by pain. Bv8/prokineticin 2 (PK2), a chemokine characterized by a unique structural motif comprising five disulfide bonds, is highly expressed in inflamed tissues associated to infiltrating cells. Here, we demonstrate the fundamental role of granulocyte-derived PK2 (GrPK2) in initiating inflammatory pain and driving peripheral sensitization. In animal models of complete Freund's adjuvant-induced paw inflammation the developme...

  13. Alpha-1-antitrypsin is produced by human neutrophil granulocytes and their precursors and liberated during granule exocytosis

    DEFF Research Database (Denmark)

    Clemmensen, Stine N; Jacobsen, Lars C; Rørvig, Sara

    2011-01-01

    Alpha-1-antitrypsin (A1AT) is an important inhibitor of neutrophil proteases including elastase, cathepsin G, and proteinase 3. Transcription profiling data suggest that A1AT is expressed by human neutrophil granulocytes during all developmental stages. A1AT has hitherto only been found associate...... significantly to the antiprotease levels in tissues during inflammation. Impaired binding of neutrophil A1AT to serine proteases in patients with (PI)ZZ mutations may enhance their susceptibility to the development of emphysema....

  14. Transplant of stem cells derived from bone marrow and granulocytic growth factor in acute and chronic ischemic myocardiopathy

    International Nuclear Information System (INIS)

    Senior Juan M; Cuellar Francisco; Velasquez Oscar; Velasquez Margarita; Navas Claudia M; Ortiz Sergio; Delgado Juan A; Guillerrno, Blanco; Londono Juan L; Coronado Manuel A; Gomez Francisco; Alzate, Fernando Leon; Zuluaga Alejandra

    2007-01-01

    Recent studies have shown the safety and efficacy of the stem cells derived from bone marrow (BMC) implant with concomitant administration of stimulating factor of granulocyte colonies in patients with acute myocardial infarction with ST segment elevation and in chronic ischemic cardiopathy. An open prospective (before and after) design was made to evaluate the safety and efficacy of cell therapy associated to growth factor administration. The first experience with this kind of therapy is reported. Methodology: this is a 6 months follow-up report of patients with acute and chronic ischemic cardiopathy to who transplant of stem cells derived from bone marrow mobilized with granulocyte colonies growth stimulating factor via coronary arteries or epicardium was realized. Two groups of patients were included: Ten patients with anterior wall infarct and 2. Five patients with chronic ischemic cardiopathy, all with extensive necrosis demonstrated by absence of myocardial viability through nuclear medicine and ejection fraction of less than 40%. Results: significant improvement of ejection fraction from 29.44 ± 3.36 to 37.6 ± 5.3 with p<0.001 and decrease of ventricular systolic and diastolic volume without statistical significance (p =0.31 and 0.4 respectively) were demonstrated. Exercise capacity evidenced by increment in the six minutes test, exercise time and the MET number achieved, increased in a significant way. There were significant changes in the perfusion defect from the second follow-up month and no complications directly related to the stem cells derived from bone marrow transplant or the use of stimulating granulocyte colony factor were presented. Conclusions: this is the first experience of stem cells derived from bone marrow transplant associated to the administration of stimulating granulocyte growth colony factor in which recovery of left ventricular function was demonstrated, as well as improvement in exercise capacity and in the perfusion defect

  15. High level of expression of recombinant human granulocyte-macrophage colony stimulating factor in transgenic rice cell suspension culture

    DEFF Research Database (Denmark)

    Shin, Yun-Ji; Hong, Shin-Young; Kwon, Tae-Ho

    2003-01-01

    Recombinant human granulocyte-macrophage colony stimulating factor (hGM-CSF) has been previously produced in tobacco cell suspension cultures. However, the amount of hGM-CSF accumulated in the culture medium dropped quickly from its maximum of 150 microg/L at 5 d after incubation. To overcome...... of recombinant hGM-CSF in transgenic rice cell suspension culture and protease activity of this culture medium was low compared to that of tobacco culture system....

  16. Inhibition of the NAD-dependent protein deacetylase SIRT2 induces granulocytic differentiation in human leukemia cells.

    Directory of Open Access Journals (Sweden)

    Yoshitaka Sunami

    Full Text Available Sirtuins, NAD-dependent protein deacetylases, play important roles in cellular functions such as metabolism and differentiation. Whether sirtuins function in tumorigenesis is still controversial, but sirtuins are aberrantly expressed in tumors, which may keep cancerous cells undifferentiated. Therefore, we investigated whether the inhibition of sirtuin family proteins induces cellular differentiation in leukemic cells. The sirtuin inhibitors tenovin-6 and BML-266 induce granulocytic differentiation in the acute promyelocytic leukemia (APL cell line NB4. This differentiation is likely caused by an inhibition of SIRT2 deacetylase activity, judging from the accumulation of acetylated α-tubulin, a major SIRT2 substrate. Unlike the clinically used differentiation inducer all-trans retinoic acid, tenovin-6 shows limited effects on promyelocytic leukemia-retinoic acid receptor α (PML-RAR-α stability and promyelocytic leukemia nuclear body formation in NB4 cells, suggesting that tenovin-6 does not directly target PML-RAR-α activity. In agreement with this, tenovin-6 induces cellular differentiation in the non-APL cell line HL-60, where PML-RAR-α does not exist. Knocking down SIRT2 by shRNA induces granulocytic differentiation in NB4 cells, which demonstrates that the inhibition of SIRT2 activity is sufficient to induce cell differentiation in NB4 cells. The overexpression of SIRT2 in NB4 cells decreases the level of granulocytic differentiation induced by tenovin-6, which indicates that tenovin-6 induces granulocytic differentiation by inhibiting SIRT2 activity. Taken together, our data suggest that targeting SIRT2 is a viable strategy to induce leukemic cell differentiation.

  17. Granulocyte-Colony Stimulating Factor (G-CSF) for stroke: an individual patient data meta-analysis

    OpenAIRE

    England, Timothy J.; Sprigg, Nikola; Alasheev, Andrey M.; Belkin, Andrey A.; Kumar, Amit; Prasad, Kameshwar; Bath, Philip M.

    2016-01-01

    Granulocyte colony stimulating factor (G-CSF) may enhance recovery from stroke through neuroprotective mechanisms if administered early, or neurorepair if given later. Several small trials suggest administration is safe but effects on efficacy are unclear. We searched for randomised controlled trials (RCT) assessing G-CSF in patients with hyperacute, acute, subacute or chronic stroke, and asked Investigators to share individual patient data on baseline characteristics, stroke severity and typ...

  18. Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

    Energy Technology Data Exchange (ETDEWEB)

    Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A. [Academy of Sciences of the Czech Republic, Inst. of Biophysics, Brno (Czech Republic); Znojil, V.; Vacha, J. [Masaryk Univ., Medical Faculty, Brno (Czech Republic)

    1998-03-01

    The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of {sup 60}Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au) 43 refs.

  19. Granulocyte colony-stimulating factor and drugs elevating extracellular adenosine synergize to enhance haematopoietic reconstitution in irradiated mice

    International Nuclear Information System (INIS)

    Pospisil, M.; Hofer, M.; Netikova, J.; Hola, J.; Vacek, A.; Znojil, V.; Vacha, J.

    1998-01-01

    The activation of adenosine receptors has recently been demonstrated to stimulate haematopoiesis. In the present study, we investigated the ability of drugs elevating extracellular adenosine to influence curative effects of granulocyte colony-stimulating factor (G-CSF) in mice exposed to a sublethal dose of 4 Gy of 60 Co radiation. Elevation of extracellular adenosine in mice was induced by the combined administration of dipyridamole, a drug inhibiting the cellular uptake of adenosine, and adenosine monophosphate (AMP), an adenosine prodrug. The effects of dipyridamole plus AMP, and G-CSF, administered either alone or in combination, were evaluated. The drugs were injected to mice in a 4-d treatment regimen starting on d 3 after irradiation and the haematopoietic response was evaluated on d 7, 10, 14, 18 and 24 after irradiation. While the effects of G-CSF on the late maturation stages of blood cells, appearing shortly after the completion of the treatment, were not influenced by dipyridamole plus AMP, positive effects of the combination therapy occurred in the post-irradiation recovery phase which is dependent on the repopulation of haematopoietic stem cells. This was indicated by the significant elevation of counts of granulocyte-macrophage progenitor cells (GM-CFC) and granulocytic cells in the bone marrow (d 14), of GM-CFC (d 14), granulocytic and erythroid cells (d 14 and 18) in the spleen, and of neutrophils (d 18), monocytes (d 14 and 18) and platelets (d 18) in the peripheral blood. These effects suggest that the repopulation potential of the combination therapy lies in a common multi-lineage cell population. The results of this study implicate the promising possibility to enhance the curative effects of G-CSF under conditions of myelosuppressive state induced by radiation exposure. (au)

  20. Use of a Granulocyte Immunofluorescence Assay Designed for Humans for Detection of Antineutrophil Cytoplasmic Antibodies in Dogs with Chronic Enteropathies.

    Science.gov (United States)

    Florey, J; Viall, A; Streu, S; DiMuro, V; Riddle, A; Kirk, J; Perazzotti, L; Affeldt, K; Wagner, R; Vaden, S; Harris, T; Allenspach, K

    2017-07-01

    Perinuclear antineutrophil cytoplasmic antibodies (pANCA) previously have been shown to be serum markers in dogs with chronic enteropathies, with dogs that have food-responsive disease (FRD) having higher frequencies of seropositivity than dogs with steroid-responsive disease (SRD). The indirect immunofluorescence (IIF) assay used in previous publications is time-consuming to perform, with low interobserver agreement. We hypothesized that a commercially available granulocyte IIF assay designed for humans could be used to detect perinuclear antineutrophil cytoplasmic antibodies in dogs. Forty-four dogs with FRD, 20 dogs with SRD, 20 control dogs, and 38 soft-coated wheaten terrier (SCWT) or SCWT-cross dogs. A granulocyte assay designed for humans was used to detect pANCA, cANCA, and antinuclear antibodies (ANA), as well as antibodies against proteinase-3 protein (PR-3) and myeloperoxidase protein (MPO) in archived serum samples. Sensitivity of the granulocyte assay to predict FRD in dogs was 0.61 (95% confidence interval (CI), 0.45, 0.75), and specificity was 1.00 (95% CI, 0.91, 1.00). A significant association was identified between positive pANCA or cANCA result and diagnosis of FRD (P < 0.0001). Agreement between the two assays to detect ANCA in the same serum samples from SCWT with protein-losing enteropathy/protein-losing nephropathy (PLE/PLN) was substantial (kappa, 0.77; 95% CI, 0.53, 1.00). Eight ANCA-positive cases were positive for MPO or PR-3 antibodies. The granulocyte immunofluorescence assay used in our pilot study was easy and quick to perform. Agreement with the previously published method was good. Copyright © 2017 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  1. Canine babesiosis in northern Portugal and molecular characterization of vector-borne co-infections

    Science.gov (United States)

    2010-01-01

    Background Protozoa and bacteria transmitted by arthropods, including ticks and phlebotomine sand flies, may cause a wide range of canine vector-borne diseases. Dogs can be simultaneously or sequentially infected with multiple pathogens. Canine babesiosis caused by Babesia canis canis and Babesia canis vogeli is known to occur in Portugal. This study assessed, by means of blood smear examination, PCR and DNA nucleotide sequencing, the presence of Babesia spp. and co-infecting agents Leishmania, Anaplasma/Ehrlichia and Hepatozoon in 45 dogs from northern Portugal clinically suspected of babesiosis. Results Forty-four dogs (98%) had infection with B. canis canis and one with B. canis vogeli. Co-infections were detected in nine animals (20%). Eight dogs were found infected with two vector-borne agents: six with B. canis canis and Leishmania infantum; one with B. canis canis and Ehrlichia canis; and one with B. canis canis and Hepatozoon canis. Another dog was infected with three vector-borne pathogens: B. canis vogeli, E. canis and L. infantum. Overall, L. infantum was found in seven (16%), E. canis in two (4%), and H. canis in one (2%) out of the 45 dogs with babesiosis. Almost 90% of the 45 cases of canine babesiosis were diagnosed in the colder months of October (18%), November (27%), December (20%), February (13%) and March (9%). Co-infections were detected in February, March, April, May, October and November. Twenty-two (50%) out of 44 dogs infected with B. canis were found infested by ticks including Dermacentor spp., Ixodes spp. and Rhipicephalus sanguineus. Mortality (9%) included two co-infected dogs that died spontaneously and two with single infections that were euthanized. Conclusions Babesia canis canis is the main etiological agent of canine babesiosis in northern Portugal. A higher sensitivity of Babesia spp. detection was obtained with PCR assays, compared to the observation of blood smears. Twenty percent of the dogs were co-infected with L. infantum

  2. Canine babesiosis in northern Portugal and molecular characterization of vector-borne co-infections

    Directory of Open Access Journals (Sweden)

    Machado João

    2010-04-01

    Full Text Available Abstract Background Protozoa and bacteria transmitted by arthropods, including ticks and phlebotomine sand flies, may cause a wide range of canine vector-borne diseases. Dogs can be simultaneously or sequentially infected with multiple pathogens. Canine babesiosis caused by Babesia canis canis and Babesia canis vogeli is known to occur in Portugal. This study assessed, by means of blood smear examination, PCR and DNA nucleotide sequencing, the presence of Babesia spp. and co-infecting agents Leishmania, Anaplasma/Ehrlichia and Hepatozoon in 45 dogs from northern Portugal clinically suspected of babesiosis. Results Forty-four dogs (98% had infection with B. canis canis and one with B. canis vogeli. Co-infections were detected in nine animals (20%. Eight dogs were found infected with two vector-borne agents: six with B. canis canis and Leishmania infantum; one with B. canis canis and Ehrlichia canis; and one with B. canis canis and Hepatozoon canis. Another dog was infected with three vector-borne pathogens: B. canis vogeli, E. canis and L. infantum. Overall, L. infantum was found in seven (16%, E. canis in two (4%, and H. canis in one (2% out of the 45 dogs with babesiosis. Almost 90% of the 45 cases of canine babesiosis were diagnosed in the colder months of October (18%, November (27%, December (20%, February (13% and March (9%. Co-infections were detected in February, March, April, May, October and November. Twenty-two (50% out of 44 dogs infected with B. canis were found infested by ticks including Dermacentor spp., Ixodes spp. and Rhipicephalus sanguineus. Mortality (9% included two co-infected dogs that died spontaneously and two with single infections that were euthanized. Conclusions Babesia canis canis is the main etiological agent of canine babesiosis in northern Portugal. A higher sensitivity of Babesia spp. detection was obtained with PCR assays, compared to the observation of blood smears. Twenty percent of the dogs were co-infected

  3. Granulocyte-Monocyte Apheresis in Steroid-Dependent, Azathioprine-Intolerant/Resistant Moderate Ulcerative Colitis: A Prospective Multicenter Study

    Directory of Open Access Journals (Sweden)

    Gianni Imperiali

    2017-01-01

    Full Text Available Background. Granulocyte-monocyte apheresis has been proposed for the treatment of ulcerative colitis, although it is limited by costs and variability of results. Aim. To assess effectiveness of granulocyte-monocyte apheresis in patients with steroid-dependent, azathioprine-intolerant/resistant moderate ulcerative colitis. Methods. Consecutive patients fulfilling inclusion criteria were prospectively enrolled, treated by apheresis, and followed up for 12 months. The primary end point of the study was steroid-free clinical remission at 12 months, with no need for biologic therapy or surgery. Results. From January to December 2013, 33 patients were enrolled. After one year of follow-up, 12 (36% patients had clinical remission, were steroid-free, and had no need for biological therapy or surgery; 3 (9% cases showed a clinical response (but not clinical remission. Moreover, 12 (36% patients required biologic therapy, 4 (12% underwent colectomy, and in the other 2 (6% a reduction, but not withdrawal, of steroid dose was achieved. Conclusions. Our study shows that a standard course of granulocyte-monocyte apheresis is associated with a 36% steroid-free clinical remission in patients with steroid-dependent, azathioprine-intolerant or resistant moderate ulcerative colitis. Apheresis might represent an alternative to biologic therapy or surgery in this specific subgroup of patients. This trial is registered with Clinicaltrial.gov NCT03189888.

  4. New mononuclear leukocyte-like populations within the granulocyte scatter gate detected by flow cytometry (Conference Presentation)

    Science.gov (United States)

    Melzer, Susanne; Löffler, Markus; Kautzner, Marlene; Tárnok, Attila

    2017-02-01

    Granulocytes are the major players in innate immunity and are prognostic markers in diseases. An in-depth phenotypic characterization of granulocyte subtypes and correlation with biometry or lifestyle is so far lacking. The reason is, that either preparation of mononuclear cells was analyzed or that cells in the neutrophil window were neglected in the analysis. Here we show for the first time lymphocyte- (LL) and monocyte-like (ML) cells within the granulocyte scatter gate as new, previously unknown cell subpopulation. Immunophenotyping of 905 healthy German adults from the LIFE study [1] was performed by 10-color flow cytometry [2]. Age of men (n=420): 56.5±14.0 years, women (n=485): 56.7±13.6 y (range of 18-81 y). Data analyzed by FlowJo v10.0.6. Values compared by Mann-Whitney-U test: men vs women, young (18-49 y) vs. elderly (50-81 y.) men, and young (19-49 y.) vs. elderly (50-81 y.) women; significance: page, except LL2 in women. In conclusion, new lymphocyte like cell types with the neutrophil scatter characteristics are reported. Counts correlate with age and gender. We plan to sort these new subtypes for further functional characterization and aim to establish them as cellular biomarkers for the early detection of various diseases. [1] BMC Public Health. 2015;15:691; [2] Cytometry A. 2014;85(9):781

  5. In vivo effect of human granulocyte-macrophage colony-stimulating factor on megakaryocytopoiesis

    International Nuclear Information System (INIS)

    Aglietta, M.; Monzeglio, C.; Sanavio, F.; Apra, F.; Morelli, S.; Stacchini, A.; Piacibello, W.; Bussolino, F.; Bagnara, G.; Zauli, G.

    1991-01-01

    The effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on megakaryocytopoiesis and platelet production was investigated in patients with normal hematopoiesis. Three findings indicated that GM-CSF plays a role in megakaryocytopoiesis. During treatment with GM-CSF (recombinant mammalian, glycosylated; Sandoz/Schering-Plough, 5.5 micrograms protein/kg/d, subcutaneously for 3 days) the percentage of megakaryocyte progenitors (megakaryocyte colony forming unit [CFU-Mk]) in S phase (evaluated by the suicide technique with high 3H-Tdr doses) increased from 31% +/- 16% to 88% +/- 11%; and the maturation profile of megakaryocytes was modified, with a relative increase in more immature stage I-III forms. Moreover, by autoradiography (after incubation of marrow cells with 125I-labeled GM-CSF) specific GM-CSF receptors were detectable on megakaryocytes. Nevertheless, the proliferative stimulus induced on the progenitors was not accompanied by enhanced platelet production (by contrast with the marked granulomonocytosis). It may be suggested that other cytokines are involved in the regulation of the intermediate and terminal stages of megakaryocytopoiesis in vivo and that their intervention is an essential prerequisite to turn the GM-CSF-induced proliferative stimulus into enhanced platelet production

  6. A comparative study of total body irradiation as a method of inducing granulocyte depletion in mice

    International Nuclear Information System (INIS)

    Bogman, M.J.J.T.; Cornelissen, I.M.H.A.; Berden, J.H.M.; Jong, J. de; Koene, R.A.P.

    1984-01-01

    Since conventional methods of inducing depletion of polymorphonuclear granulocytes (PMNs) in mice, such as treatment with cytostatic drugs and anti-PMN sera, proved to be insufficient to induce a stable PMN depletion for several days, and were accompanied by considerable toxic side effects, we induced neutrophil depletion in mice by total body irradiation (TBI) in a single dose of 6.0 Gy (600 rads.) at a dose rate of 0.20 Gy/min. This treatment reduced the number of PMNs in the peripheral circulation to values below 150/μl from day 3-10 after irradiation. The number of lymphocytes fell simultaneously. Platelet counts remained above 60% of normal values during the first 7 days after irradiation. Complement levels were not significantly affected by TBI. The results show that TBI of 6.0 Gy induces pronounced and stable PMN depletion in mice for at least 7 days. Furthermore, under an aseptic regimen the mice can be kept in good condition and losses are less than 5%. (Auth.)

  7. Long-active granulocyte colony-stimulating factor for peripheral blood hematopoietic progenitor cell mobilization.

    Science.gov (United States)

    Martino, Massimo; Laszlo, Daniele; Lanza, Francesco

    2014-06-01

    Peg-filgrastim (PEG-FIL), a polyethylene glycol-conjugated form of granulocyte colony-stimulating factor (G-CSF), has been introduced in clinical practice and is effective in shortening the time of neutropenia after cytotoxic chemotherapy. G-CSF has emerged as the preferred cytokine for hematopoietic progenitor cells' (HPC) mobilization. Nevertheless, data on the ability of PEG-FIL in this field have been published. We review publications in the field with the goal of providing an overview of this approach. PEG-FIL may be able to mobilize CD34(+) cells in a more timely fashion than G-CSF, with the advantages of only a single-dose administration, an earlier start and a reduction in the number of apheresis procedures. The main controversies concern the dosage of the drug and the optimal dose. In the context of chemo-mobilization, a single dose of 6 mg PEG-FIL seems effective in terms of HPC's mobilization and there is no increase in this effect if the dose is doubled to 12 mg. Steady-state mobilization requires higher doses of PEG-FIL and this approach is not cost-effective when compared with G-CSF. The experiences with PEG-FIL in the healthy donor setting are very limited.

  8. Human granulocyte colony-stimulating factor (hG-CSF) expression in plastids of Lactuca sativa.

    Science.gov (United States)

    Sharifi Tabar, Mehdi; Habashi, Ali Akbar; Rajabi Memari, Hamid

    2013-01-01

    Human granulocyte colony-stimulating factor (hG-CSF) can serve as valuable biopharmaceutical for research and treatment of the human blood cancer. Transplastomic plants have been emerged as a new and high potential candidate for production of recombinant biopharmaceutical proteins in comparison with transgenic plants due to extremely high level expression, biosafety and many other advantages. hG-CSF gene was cloned into pCL vector between prrn16S promoter and TpsbA terminator. The recombinant vector was coated on nanogold particles and transformed to lettuce chloroplasts through biolistic method. Callogenesis and regeneration of cotyledonary explants were obtained by Murashige and Skoog media containing 6-benzylaminopurine and 1-naphthaleneacetic acid hormones. The presence of hG-CSF gene in plastome was studied with four specific PCR primers and expression by Western immunoblotting. hG-CSF gene cloning was confirmed by digestion and sequencing. Transplastomic lettuce lines were regenerated and subjected to molecular analysis. The presence of hG-CSF in plastome was confirmed by PCR using specific primers designed from the plastid genome. Western immunoblotting of extracted protein from transplastomic plants showed a 20-kDa band, which verified the expression of recombinant protein in lettuce chloroplasts. This study is the first report that successfully express hG-CSF gene in lettuce chloroplast. The lettuce plastome can provide a cheap and safe expression platform for producing valuable biopharmaceuticals for research and treatment.

  9. Granulocyte-colony stimulating factor controls neural and behavioral plasticity in response to cocaine.

    Science.gov (United States)

    Calipari, Erin S; Godino, Arthur; Peck, Emily G; Salery, Marine; Mervosh, Nicholas L; Landry, Joseph A; Russo, Scott J; Hurd, Yasmin L; Nestler, Eric J; Kiraly, Drew D

    2018-01-16

    Cocaine addiction is characterized by dysfunction in reward-related brain circuits, leading to maladaptive motivation to seek and take the drug. There are currently no clinically available pharmacotherapies to treat cocaine addiction. Through a broad screen of innate immune mediators, we identify granulocyte-colony stimulating factor (G-CSF) as a potent mediator of cocaine-induced adaptations. Here we report that G-CSF potentiates cocaine-induced increases in neural activity in the nucleus accumbens (NAc) and prefrontal cortex. In addition, G-CSF injections potentiate cocaine place preference and enhance motivation to self-administer cocaine, while not affecting responses to natural rewards. Infusion of G-CSF neutralizing antibody into NAc blocks the ability of G-CSF to modulate cocaine's behavioral effects, providing a direct link between central G-CSF action in NAc and cocaine reward. These results demonstrate that manipulating G-CSF is sufficient to alter the motivation for cocaine, but not natural rewards, providing a pharmacotherapeutic avenue to manipulate addictive behaviors without abuse potential.

  10. A scanning electron microscopic study of 34 cases of acute granulocytic, myelomonocytic, monoblastic and histiocytic leukemia.

    Science.gov (United States)

    Polliack, A; McKenzie, S; Gee, T; Lampen, N; de Harven, E; Clarkson, B D

    1975-09-01

    This report describes the surface architecture of leukemic cells, as seen by scanning electron microscopy in 34 patients with acute nonlymphoblastic leukemia. Six patients with myeloblastic, 4 with promyelocytic, 10 with myelomonocytic, 8 with monocytic, 4 with histiocytic and 2 with undifferentiated leukemia were studied. Under the scanning electron microscope most leukemia histiocytes and monocytes appeared similar and were characterized by the presence of large, well developed broad-based ruffled membranes or prominent raised ridge-like profiles, resembling ithis respect normal monocytes. Most cells from patients with acute promyelocytic or myeloblastic leukemia exhibited narrower ridge-like profiles whereas some showed ruffles or microvilli. Patients with myelomonocytic leukemia showed mixed populations of cells with ridge-like profiles and ruffled membranes whereas cells from two patients with undifferentiated leukemia had smooth surfaces, similar to those encountered in cells from patients with acute lymphoblastic leukemia. It appears that nonlymphoblastic and lymphoblastic leukemia cells (particularly histiocytes and monocytes) can frequently be distinquished on the basis of their surface architecture. The surface features of leukemic histiocytes and monocytes are similar, suggesting that they may belong to the same cell series. The monocytes seem to have characteristic surface features recognizable with the scanning electron microscope and differ from most cells from patients with acute granulocytic leukemia. Although overlap of surface features and misidentification can occur, scanning electron microscopy is a useful adjunct to other modes of microscopy in the study and diagnosis of acute leukemia.

  11. Does granulocyte colony-stimulating factor exacerbate radiation-induced acute lung injury in rats?

    International Nuclear Information System (INIS)

    Miura, Gouji; Awaya, Hitomi; Matsumoto, Tsuneo; Tanaka, Nobuyuki; Matsunaga, Naofumi

    2000-01-01

    Radiation pneumonitis (RP) frequently occurs as a complication of thoracic irradiation. However, the mechanism of RP is not well known. Activated neutrophils are a possible pathogenesis of RP. Neutrophil activation induced by granulocyte colony-stimulating factor (G-CSF) may exacerbate RP. We studied the effects of recombinant human G-CSF on acute lung injury induced by thoracic irradiation using rats. Animals were divided into three groups: sham irradiation with saline control, irradiation alone, and irradiation with G-CSF. Actual irradiation was given as a single fraction of 16 Gy delivered to the right hemithorax. G-CSF at a dose of 12 μg/body was administered subcutaneously once a day from 14 to 18 days after actual irradiation. Lung injury was evaluated 21 days after irradiation by bronchoalveolar lavage (BAL) fluid findings and the lung wet/dry weight (W/D) ratio. Neutrophil and lymphocyte counts in BAL fluid and the W/D ratio were significantly increased in the irradiation alone and the irradiation with G-CSF groups compared with those of the sham irradiation+saline control group. However, there was no significant difference observed between the irradiation alone and irradiation with G-CSF groups. In conclusion, this study suggests that postradiation administration of G-CSF does not exacerbate acute lung injury induced by thoracic irradiation in rats. (author)

  12. Development and characterization of antiserum to murine granulocyte-macrophage colony-stimulating factor

    International Nuclear Information System (INIS)

    Mochizuki, D.Y.; Eisenman, J.R.; Conlon, P.J.; Park, L.S.; Urdal, D.L.

    1986-01-01

    The expression in yeast of a cDNA clone encoding murine granulocyte-macrophage colony-stimulating factor (GM-CSF) has made possible the purification of large quantities of this recombinant protein. Rabbits immunized with pure recombinant GM-CSF generated antibodies that were shown to be specific for both recombinant GM-CSF and GM-CSF isolated from natural sources. Other lymphokines, including IL 1β, IL 2, IL 3, and recombinant human GM-CSF did not react with the antiserum. The antiserum together with recombinant GM-CSF that had been radiolabeled with 125 I to high specific activity, formed the foundation for a rapid, sensitive, and quantitative radioimmunoassay specific for murine GM-CSF. Furthermore, the antiserum was found to inhibit the biologic activities of GM-CSF as measured in both a bone marrow proliferation assay and a colony assay, and thus should prove to be a useful reagent for dissecting the complex growth factor activities involved in murine hematopoiesis

  13. Increased FasL expression correlates with apoptotic changes in granulocytes cultured with oxidized clozapine

    International Nuclear Information System (INIS)

    Husain, Zaheed; Almeciga, Ingrid; Delgado, Julio C.; Clavijo, Olga P.; Castro, Januario E.; Belalcazar, Viviana; Pinto, Clara; Zuniga, Joaquin; Romero, Viviana; Yunis, Edmond J.

    2006-01-01

    Clozapine has been associated with a 1% incidence of agranulocytosis. The formation of an oxidized intermediate clozapine metabolite has been implicated in direct polymorphonuclear (PMN) toxicity. We utilized two separate systems to analyze the role of oxidized clozapine in inducing apoptosis in treated cells. Human PMN cells incubated with clozapine (0-10 μM) in the presence of 0.1 mM H 2 O 2 demonstrated a progressive decrease of surface CD16 expression along with increased apoptosis. RT-PCR analysis showed decreased CD16 but increased FasL gene expression in clozapine-treated PMN cells. No change in constitutive Fas expression was observed in treated cells. In HL-60 cells induced to differentiate with retinoic acid (RA), a similar increase in FasL expression, but no associated changes in CD16 gene expression, was observed following clozapine treatments. Our results demonstrate increased FasL gene expression in oxidized clozapine-induced apoptotic neutrophils suggesting that apoptosis in granulocytes treated with clozapine involves Fas/FasL interaction that initiates a cascade of events leading to clozapine-induced agranulocytosis

  14. Expression of granulocyte colony-stimulating factor receptor correlates with prognosis in oral and mesopharyngeal carcinoma.

    Science.gov (United States)

    Tsuzuki, H; Fujieda, S; Sunaga, H; Noda, I; Saito, H

    1998-02-15

    Granulocyte colony-stimulating factor receptors (G-CSFRs) have been observed on the surface of not only hematopoietic cells but also several cancer cells. The stimulation of G-CSF has been demonstrated to induce proliferation and activation of G-CSFR-positive cells. In this study, we investigated the expression of G-CSFR on the surface of tumor cells and G-CSF production in oral and mesopharyngeal squamous cell carcinoma (SCC) by an immunohistochemical approach. Of 58 oral and mesopharyngeal SCCs, 31 cases (53.4%) and 36 cases (62.1%) were positive for G-CSFR and G-CSF, respectively. There was no association between G-CSFR expression and G-CSF staining. In the group positive for G-CSFR expression, relapse was significantly more likely after primary treatment (P = 0.0069), whereas there was no association between G-CSFR expression and age, sex, tumor size, lymph node metastasis, and clinical stage. Also, the G-CSFR-positive groups had a significantly lower disease-free and overall survival rate than the G-CSFR-negative groups (P = 0.0172 and 0.0188, respectively). However, none of the clinical markers correlated significantly with G-CSF staining, nor did the status of G-CSF production influence the overall survival. The results imply that assessment of G-CSFR may prove valuable in selecting patients with oral and mesopharyngeal SCC for aggressive therapy.

  15. Fluorine-18 fluorodeoxyglucose splenic uptake from extramedullary hematopoiesis after granulocyte colony-stimulating factor stimulation.

    Science.gov (United States)

    Abdel-Dayem, H M; Rosen, G; El-Zeftawy, H; Naddaf, S; Kumar, M; Atay, S; Cacavio, A

    1999-05-01

    Two patients with sarcoma, one with recurrent osteosarcoma of the spine and the other with metastatic synovial cell sarcoma, were treated with high-dose chemotherapy that produced severe leukopenia. The patients received granulocyte colony-stimulating factor (G-CSF) to stimulate the bone marrow (480 mg given subcutaneously twice daily for 5 to 7 days); their responses were seen as a marked increase in peripheral leukocyte count with no change in the erythrocyte or platelet counts. The patients had fluorine-18 fluorodeoxyglucose (F-18 FDG) imaging 24 hours after the end of G-CSF treatment. Diffusely increased uptake of F-18 FDG was seen in the bone marrow in both patients. In addition, markedly increased uptake in the spleen was noted in both, indicating that the spleen was the site of extramedullary hematopoiesis. The patients had no evidence of splenic metastases. The first patient had a history of irradiation to the dorsal spine, which was less responsive to G-CSF administration than was the nonirradiated lumbar spine.

  16. Monocytic and granulocytic myeloid derived suppressor cells differentially regulate spatiotemporal tumour plasticity during metastatic cascade.

    Science.gov (United States)

    Ouzounova, Maria; Lee, Eunmi; Piranlioglu, Raziye; El Andaloussi, Abdeljabar; Kolhe, Ravindra; Demirci, Mehmet F; Marasco, Daniela; Asm, Iskander; Chadli, Ahmed; Hassan, Khaled A; Thangaraju, Muthusamy; Zhou, Gang; Arbab, Ali S; Cowell, John K; Korkaya, Hasan

    2017-04-06

    It is widely accepted that dynamic and reversible tumour cell plasticity is required for metastasis, however, in vivo steps and molecular mechanisms are poorly elucidated. We demonstrate here that monocytic (mMDSC) and granulocytic (gMDSC) subsets of myeloid-derived suppressor cells infiltrate in the primary tumour and distant organs with different time kinetics and regulate spatiotemporal tumour plasticity. Using co-culture experiments and mouse transcriptome analyses in syngeneic mouse models, we provide evidence that tumour-infiltrated mMDSCs facilitate tumour cell dissemination from the primary site by inducing EMT/CSC phenotype. In contrast, pulmonary gMDSC infiltrates support the metastatic growth by reverting EMT/CSC phenotype and promoting tumour cell proliferation. Furthermore, lung-derived gMDSCs isolated from tumour-bearing animals enhance metastatic growth of already disseminated tumour cells. MDSC-induced 'metastatic gene signature' derived from murine syngeneic model predicts poor patient survival in the majority of human solid tumours. Thus spatiotemporal MDSC infiltration may have clinical implications in tumour progression.

  17. Structural analysis of the receptors for granulocyte colony-stimulating factor on neutrophils

    International Nuclear Information System (INIS)

    Hanazono, Y.; Hosoi, T.; Kuwaki, T.; Matsuki, S.; Miyazono, K.; Miyagawa, K.; Takaku, F.

    1990-01-01

    We investigated granulocyte colony-stimulating factor (G-CSF) receptors on neutrophils from three patients with chronic myelogenous leukemia (CML) in the chronic phase, in comparison with four normal volunteers. Because we experienced some difficulties in radioiodinating intact recombinant human G-CSF, we developed a new derivative of human G-CSF termed YPY-G-CSF. It was easy to iodinate this protein using the lactoperoxidase method because of two additional tyrosine residues, and its radioactivity was higher than that previously reported. The biological activity of YPY-G-CSF as G-CSF was fully retained. Scatchard analysis demonstrated that CML neutrophils had a single class of binding sites (1400 +/- 685/cell) with a dissociation constant (Kd) of 245 +/- 66 pM. The number of sites and Kd value of CML neutrophils were not significantly different from those of normal neutrophils (p greater than 0.9). Cross-linking studies revealed two specifically labeled bands of [125I]YPY-G-CSF-receptor complexes with apparent molecular masses of 160 and 110 kd on both normal and CML neutrophils. This is the first report describing two receptor proteins on neutrophils. According to the analyses of the proteolytic process of these cross-linked complexes and proteolytic mapping, we assume that alternative splicing or processing from a single gene may generate two distinct receptor proteins that bind specifically to G-CSF but have different fates in intracellular metabolism

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

    Science.gov (United States)

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

  19. Does granulocyte colony-stimulating factor exacerbate radiation-induced acute lung injury in rats?

    Energy Technology Data Exchange (ETDEWEB)

    Miura, Gouji; Awaya, Hitomi; Matsumoto, Tsuneo; Tanaka, Nobuyuki; Matsunaga, Naofumi [Yamaguchi Univ., Ube (Japan). School of Medicine

    2000-08-01

    Radiation pneumonitis (RP) frequently occurs as a complication of thoracic irradiation. However, the mechanism of RP is not well known. Activated neutrophils are a possible pathogenesis of RP. Neutrophil activation induced by granulocyte colony-stimulating factor (G-CSF) may exacerbate RP. We studied the effects of recombinant human G-CSF on acute lung injury induced by thoracic irradiation using rats. Animals were divided into three groups: sham irradiation with saline control, irradiation alone, and irradiation with G-CSF. Actual irradiation was given as a single fraction of 16 Gy delivered to the right hemithorax. G-CSF at a dose of 12 {mu}g/body was administered subcutaneously once a day from 14 to 18 days after actual irradiation. Lung injury was evaluated 21 days after irradiation by bronchoalveolar lavage (BAL) fluid findings and the lung wet/dry weight (W/D) ratio. Neutrophil and lymphocyte counts in BAL fluid and the W/D ratio were significantly increased in the irradiation alone and the irradiation with G-CSF groups compared with those of the sham irradiation+saline control group. However, there was no significant difference observed between the irradiation alone and irradiation with G-CSF groups. In conclusion, this study suggests that postradiation administration of G-CSF does not exacerbate acute lung injury induced by thoracic irradiation in rats. (author)

  20. Effect of Temperature on Granulocyte and Monocyte Adsorption to Cellulose Acetate Beads.

    Science.gov (United States)

    Nishise, Shoichi; Takeda, Yuji; Abe, Yasuhiko; Sasaki, Yu; Nara, Hidetoshi; Asao, Hironobu; Ueno, Yoshiyuki

    2017-06-01

    Granulocyte and monocyte (GM) adsorptive apheresis (GMA) is an effective therapy for inflammatory disorders including inflammatory bowel disease (IBD). During GMA, the blood of a patient with IBD passes through a column to contact cellulose acetate (CA) beads at a temperature below body temperature, likely close to room temperature. Here we investigated the effect of temperature on GM adsorption to CA beads in vitro. We incubated peripheral blood with and without CA beads at 5°C, 25°C, 37°C, and 43°C and calculated the ratios of adsorbed GMs. The ratios of adsorbed GMs increased as the temperature was raised. Additionally, we measured complement activation fragment concentrations. C3a and C5a concentrations also increased as the temperature was raised, and C5a concentrations had a positive correlation with the ratios of adsorbed GMs. These results suggest that warming the column during GMA might increase GM adsorption to CA beads, thereby enhancing the clinical efficacy of GMA. © 2017 International Society for Apheresis, Japanese Society for Apheresis, and Japanese Society for Dialysis Therapy.

  1. The effect of long-term treatment with granulocyte colony-stimulating factor on hematopoiesis in HIV-infected individuals

    DEFF Research Database (Denmark)

    Nielsen, S D; Sørensen, T U; Aladdin, H

    2000-01-01

    of G-CSF on in vivo function of progenitors the white-blood count was determined. Significant increase in white-blood count was found (P hemoglobin and platelet count decreased (P = 0.001 and P = 0.013, respectively). Significant increase in the CD4 count occurred, but correlation...

  2. Involvement of the histamine H4 receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

    International Nuclear Information System (INIS)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake; Ozaki, Norio; Noda, Yukihiro

    2016-01-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H 4 receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H 4 receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H 4 receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H 4 receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation. - Highlights: • HL-60

  3. Involvement of the histamine H{sub 4} receptor in clozapine-induced hematopoietic toxicity: Vulnerability under granulocytic differentiation of HL-60 cells

    Energy Technology Data Exchange (ETDEWEB)

    Goto, Aya; Mouri, Akihiro; Nagai, Tomoko; Yoshimi, Akira; Ukigai, Mako; Tsubai, Tomomi; Hida, Hirotake [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan); Ozaki, Norio [Department of Psychiatry, Graduate School of Medicine, Nagoya University, 65 Tsurumai-cho, Showa-ku, Nagoya 466-8550 (Japan); Noda, Yukihiro, E-mail: ynoda@meijo-u.ac.jp [Division of Clinical Sciences and Neuropsychopharmacology, Faculty and Graduate School of Pharmacy, Meijo University, 150 Yagotoyama, Tempaku-ku, Nagoya 468-8503 (Japan)

    2016-09-01

    Clozapine is an effective antipsychotic for treatment-resistant schizophrenia, but can cause fatal hematopoietic toxicity as agranulocytosis. To elucidate the mechanism of hematopoietic toxicity induced by clozapine, we developed an in vitro assay system using HL-60 cells, and investigated the effect on hematopoiesis. HL-60 cells were differentiated by all-trans retinoic acid (ATRA) into three states according to the following hematopoietic process: undifferentiated HL-60 cells, those undergoing granulocytic ATRA-differentiation, and ATRA-differentiated granulocytic cells. Hematopoietic toxicity was evaluated by analyzing cell survival, cell proliferation, granulocytic differentiation, apoptosis, and necrosis. In undifferentiated HL-60 cells and ATRA-differentiated granulocytic cells, both clozapine (50 and 100 μM) and doxorubicin (0.2 µM) decreased the cell survival rate, but olanzapine (1–100 µM) did not. Under granulocytic differentiation for 5 days, clozapine, even at a concentration of 25 μM, decreased survival without affecting granulocytic differentiation, increased caspase activity, and caused apoptosis rather than necrosis. Histamine H{sub 4} receptor mRNA was expressed in HL-60 cells, whereas the expression decreased under granulocytic ATRA-differentiation little by little. Both thioperamide, a histamine H{sub 4} receptor antagonist, and DEVD-FMK, a caspase-3 inhibitor, exerted protection against clozapine-induced survival rate reduction, but not of live cell counts. 4-Methylhistamine, a histamine H{sub 4} receptor agonist, decreased the survival rate and live cell counts, as did clozapine. HL-60 cells under granulocytic differentiation are vulnerable under in vitro assay conditions to hematopoietic toxicity induced by clozapine. Histamine H{sub 4} receptor is involved in the development of clozapine-induced hematopoietic toxicity through apoptosis, and may be a potential target for preventing its occurrence through granulocytic differentiation

  4. Imaging infection and inflammation

    International Nuclear Information System (INIS)

    Buscombe, John

    1997-01-01

    imaging acute infection on the intensive therapy unit or to reduce radiation dose in the monitoring of a child with inflammatory bowel disease who had to suffer the indignity of a colonoscopy or a barium enema. We also look forward to newer techniques, certainly the use of immuno globulins, both pooled human and monoclonal antibodies directed either against leukocytes or a specific pathogen may prove useful. The new molecular medicine is starting to exploit our knowledge of the mechanisms of infection and inflammation. It may be possible to produce artificial peptides to localize at sites of infections and/or inflammation. Simpler techniques such as radio labelled antibiotics may be the answer. At present one such antibiotic, a quinilone labelled with Technetium-99 m (called infecton) in undergoing an international IAEA trial. A more complex approach will be the use of radio labelled drugs wrapped in 'stealth'liposomes to avoid liver uptake but deliver the pharmaceutical to the granulocyte in vivo. All are under development. We must however also deliver the best clinical service we can at present delivering accurate results with the lowest radiation dose and available when the patient needs it. As such Tc-99 m HMPAO labelled leukocytes and Gallium-67 are still probably the methods of choice in most situations thoung this may be tempered by local needs and factors

  5. A Preliminary Parasitological Survey of Hepatozoon Spp. Infection in Dogs in Mashhad, Iran

    Directory of Open Access Journals (Sweden)

    J Khoshnegah

    2012-12-01

    Full Text Available Background: We attempted to determine the prevalence of Hepatozoon spp. infection in Mashhad, northeast of Iran, via blood smear parasitology.Methods: The prevalence was investigated by examination of blood smear parasitology, using blood samples collected from 254 dogs (51 strays and 203 privately owned-dogs.Results: Two stray dogs (2/51; 3.92% and two privately-owned dogs (2/203; 0.98% were infected with Hepatozoon spp. Therefore, as per blood smear parasitology, the prevalence of Hepatozoon spp. infection was 1.57% (4/254. Sixteen out of 254 dogs (6.29% were infested with ticks; all of which were Rhipicephalus sanguineus. One of the dogs infected with Hepatozoon spp. exhibited ticks at the time of examination. Concurrent infection with Ehrlichia canis and Leishmania infantum was not detected in the four Hepatozoon spp. infected dogs.Conclusion: This is the first epidemiological study on the prevalence of Hepatozoon spp. infection in dogs in Iran.

  6. Vaginal Infections

    Science.gov (United States)

    ... gov/ Home Body Your reproductive health Vaginal infections Vaginal infections Help for infections If you have pain, ... infections and how to prevent them. Types of vaginal infections top Two common vaginal infections are bacterial ...

  7. Infective Endocarditis

    Science.gov (United States)

    ... Center > Infective Endocarditis Menu Topics Topics FAQs Infective Endocarditis En español Infective endocarditis is an infection of ... time, congestive heart failure (CHF). What causes infective endocarditis? The infection that leads to endocarditis can be ...

  8. Effects of human granulocyte-colony stimulating factor on fracture healing in rats

    International Nuclear Information System (INIS)

    Bozlar, M.; Aslan, B.; Kalaci, A.; Yanat, Ahmet N.; Baktiroglu, L.; Tasci, A.

    2005-01-01

    Granulocyte colony stimulation factor (G-CSF) is generally used to prevent and cure the neutropenia associated with chemotherapy and bone marrow transplantation. In addition to its effects on neutrophil function, G-CSF was found to have the characteristic of modulating the cytokines in the inflammatory response. Then, the question to answer is whether it has any effect on fracture healing and to what extent? In this study, we test the effects of G-CSF on the healing of tibia fracture in a rat model. This study was performed at Harran University, Sanliurfa, Turkey between July 2003 and August 2004. Twenty female, healthy Sprague-Dawley rats, weighing between 250 and 300 gm were divided into 2 groups, and their tibiae broken. The rats in the G-CSF group were injected subcutaneous with 25ug/kg/day of recombinant human G-CSF for 7 days, and the ones in the control group with 0.9% sodium chloride. Rats were sacrificed 3 weeks after surgery and then radiological, histological and biomechanical evaluations were performed. Biomechanical tests were performed at the Middle East Technical University, Ankara, Turkey.The median radiographic scores for the control group were calculated as 4.1, and 6.1 for the G-CSF group (p = 0.016). Cortex remodeling, callus formation, bone union and marrow changes values did not differ significantly (p > 0.05). Mechanical parameter (mean max-Load) values for the control group were found to be 24.0 +/- 3.0 N, and 241.5 +/-75.7 N for the G-CSF group (p 0.001). We found that G-CSF has an important effect on fracture healing. However, this effect requires further study. (author)

  9. Granulocyte macrophage colony stimulating factor (GM-CSF biological actions on human dermal fibroblasts

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    S Montagnani

    2009-12-01

    Full Text Available Fibroblasts are involved in all pathologies characterized by increased ExtraCellularMatrix synthesis, from wound healing to fibrosis. Granulocyte Macrophage-Colony Stimulating Factor (GM-CSF is a cytokine isolated as an hemopoietic growth factor but recently indicated as a differentiative agent on endothelial cells. In this work we demonstrated the expression of the receptor for GM-CSF (GMCSFR on human normal skin fibroblasts from healthy subjects (NFPC and on a human normal fibroblast cell line (NHDF and we try to investigate the biological effects of this cytokine. Human normal fibroblasts were cultured with different doses of GM-CSF to study the effects of this factor on GMCSFR expression, on cell proliferation and adhesion structures. In addition we studied the production of some Extra-Cellular Matrix (ECM components such as Fibronectin, Tenascin and Collagen I. The growth rate of fibroblasts from healthy donors (NFPC is not augmented by GM-CSF stimulation in spite of increased expression of the GM-CSFR. On the contrary, the proliferation of normal human dermal fibroblasts (NHDF cell line seems more influenced by high concentration of GM-CSF in the culture medium. The adhesion structures and the ECM components appear variously influenced by GM-CSF treatment as compared to fibroblasts cultured in basal condition, but newly only NHDF cells are really induced to increase their synthesis activity. We suggest that the in vitro treatment with GM-CSF can shift human normal fibroblasts towards a more differentiated state, due or accompanied by an increased expression of GM-CSFR and that such “differentiation” is an important event induced by such cytokine.

  10. Time-dependent labelling course of human eosinophilic granulocytes after 3H thymidine application

    International Nuclear Information System (INIS)

    Walle, A.J.

    1975-01-01

    After intravenous injection of 0.1 μCi/g body weight 3 H-Thymidine and taking of blood samples in intervals of 6-12 hrs. on three test persons with healthy blood, the labelling course of the eosinophilic granulocytes was studied. The cells were classified in four groups, according to the relative frequency of the different degrees of labelling. The time-dependent labelling index curves showed a nawe-sheped course. Elimination of the eosinophilics from the blood is carried out according to the 'At-random'-principle. 12 hrs. p.i. already 10% of the eosinophilics in the blood were labelled with maximally 5 grains. The cell flow-in phase of 13 hrs. was succeeded by a flow-out phase of nearly the same duration, afthr the first labelling maximum of 17%. 80 hrs. p.i. the first massive in-flow of high-labelled cells containing more than 30 grains. After reaching the labelling maximum of 58%, the labelling index values decreased continuously. Until the 11th day p.i., appr. 50% of the eosinophilics were still labelled, after 17 days appr. 25%, more than 65% of which consisted of cells with only 2-4 grains. Comparison of the labelling index curves of the grain groups with each other shows at first a synchronous, then an increasingly asynchronous course, according to the desynchronization of the several eosinophilic generation cycles in the bone marrow which gets more significant in the course of time. (orig.) [de

  11. Isolated granulocytic sarcoma of the nasopharynx: a case report and review of the literature

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    Vishnu P

    2013-12-01

    Full Text Available Prakash Vishnu,1 Ravindra Reddy Chuda,2 Dick G Hwang,3 David M Aboulafia1,4 1Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center, Seattle, WA, USA; 2Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA; 3Department of Pathology, Virginia Mason Medical Center, 4Division of Hematology, University of Washington, Seattle, WA, USA Abstract: Granulocytic sarcoma (GS is a rare extramedullary manifestation of acute myeloid leukemia (AML. It may also represent blastic transformation of myelodysplastic syndromes or myeloproliferative neoplasms. Although usually seen in the context of advanced and poorly controlled disease, it may also present as the first manifestation of illness, without concurrent bone marrow or blood involvement. In the medical literature, chloroma and GS are terms that have been used interchangeably with myeloid sarcoma. GS usually manifests as soft tissue or bony masses in several extracranial sites, such as bone, periosteum, and lymph nodes; involvement of the head and neck region is uncommon. We report a case of a woman with insidious onset of progressive nasal congestion and diminished hearing who was diagnosed with an isolated GS of the nasopharynx. With involved field radiotherapy, she achieved a complete remission of 12-months duration before being diagnosed with overt AML. She has remained disease-free for greater than 18 months following induction and consolidation chemotherapy. Through a MEDLINE®/PubMed® search we identified an additional 13 cases of nasopharyngeal GS. The median age was 37 years (range 1 to 81 years. The cases were equally distributed among the sexes. The most common presenting symptoms were conductive hearing loss and sinonasal congestion. Isolated GS was identified in six cases, and the median time from diagnosis of GS to AML was 12 months (range 3 to 48 months. The treatment varied, but responses were seen in all the patients who received

  12. Frequencies, Laboratory Features, and Granulocyte Activation in Chinese Patients with CALR-Mutated Myeloproliferative Neoplasms.

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    Haixiu Guo

    Full Text Available Somatic mutations in the CALR gene have been recently identified as acquired alterations in myeloproliferative neoplasms (MPNs. In this study, we evaluated mutation frequencies, laboratory features, and granulocyte activation in Chinese patients with MPNs. A combination of qualitative allele-specific polymerase chain reaction and Sanger sequencing was used to detect three driver mutations (i.e., CALR, JAK2V617F, and MPL. CALR mutations were identified in 8.4% of cases with essential thrombocythemia (ET and 5.3% of cases with primary myelofibrosis (PMF. Moreover, 25% of polycythemia vera, 29.5% of ET, and 48.1% of PMF were negative for all three mutations (JAK2V617F, MPL, and CALR. Compared with those patients with JAK2V617F mutation, CALR-mutated ET patients displayed unique hematological phenotypes, including higher platelet counts, and lower leukocyte counts and hemoglobin levels. Significant differences were not found between Chinese PMF patients with mutants CALR and JAK2V617F in terms of laboratory features. Interestingly, patients with CALR mutations showed markedly decreased levels of leukocyte alkaline phosphatase (LAP expression, whereas those with JAK2V617F mutation presented with elevated levels. Overall, a lower mutant rate of CALR gene and a higher triple-negative rate were identified in the cohort of Chinese patients with MPNs. This result indicates that an undiscovered mutant gene may have a significant role in these patients. Moreover, these pathological features further imply that the disease biology varies considerably between mutants CALR and JAK2V617F.

  13. Granulocyte colony-stimulating factor in repeated IVF failure, a randomized trial.

    Science.gov (United States)

    Aleyasin, Ashraf; Abediasl, Zhila; Nazari, Atefeh; Sheikh, Mahdi

    2016-06-01

    Recent studies have revealed key roles for granulocyte colony-stimulating factor (GCSF) in embryo implantation process and maintenance of pregnancy, and some studies showed promising results by using local intrauterine infusion of GCSF in patients undergoing in vitro fertilization (IVF). This multicenter, randomized, controlled trial included 112 infertile women with repeated IVF failure to evaluate the efficacy of systemic single-dose subcutaneous GCSF administration on IVF success in these women. In this study, the Long Protocol of ovarian stimulation was used for all participants. Sealed, numbered envelopes assigned 56 patients to receive subcutaneous 300 µg GCSF before implantation and 56 in the control group. The implantation (number of gestational sacs on the total number of transferred embryos), chemical pregnancy (positive serum β-HCG), and clinical pregnancy (gestational sac and fetal heart) rates were compared between the two groups. This trial is registered at www.irct.ir (IRCT201503119568N11). The successful implantation (18% vs 7.2%, P=0.007), chemical pregnancy (44.6% vs 19.6%, P=0.005), and clinical pregnancy (37.5% vs 14.3%, P=0.005) rates were significantly higher in the intervention group than in the control group. After adjustment for participants' age, endometrial thickness, good-quality oocyte counts, number of transferred embryos, and anti-Mullerian hormone levels, GCSF treatment remained significantly associated with successful implantation (OR=2.63, 95% CI=1.09-6.96), having chemical pregnancy (OR= 2.74, 95% CI=1.11-7.38) and clinical pregnancy (OR=2.94, 95% CI=1.23-8.33). In conclusion, administration of single-dose systemic subcutaneous GCSF before implantation significantly increases the IVF success, implantation, and pregnancy rates in infertile women with repeated IVF failure. © 2016 Society for Reproduction and Fertility.

  14. Granulocyte colony stimulating factor attenuates inflammation in a mouse model of amyotrophic lateral sclerosis

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    Giniatullina Raisa

    2011-06-01

    Full Text Available Abstract Background Granulocyte colony stimulating factor (GCSF is protective in animal models of various neurodegenerative diseases. We investigated whether pegfilgrastim, GCSF with sustained action, is protective in a mouse model of amyotrophic lateral sclerosis (ALS. ALS is a fatal neurodegenerative disease with manifestations of upper and lower motoneuron death and muscle atrophy accompanied by inflammation in the CNS and periphery. Methods Human mutant G93A superoxide dismutase (SOD1 ALS mice were treated with pegfilgrastim starting at the presymptomatic stage and continued until the end stage. After long-term pegfilgrastim treatment, the inflammation status was defined in the spinal cord and peripheral tissues including hematopoietic organs and muscle. The effect of GCSF on spinal cord neuron survival and microglia, bone marrow and spleen monocyte activation was assessed in vitro. Results Long-term pegfilgrastim treatment prolonged mutant SOD1 mice survival and attenuated both astro- and microgliosis in the spinal cord. Pegfilgrastim in SOD1 mice modulated the inflammatory cell populations in the bone marrow and spleen and reduced the production of pro-inflammatory cytokine in monocytes and microglia. The mobilization of hematopoietic stem cells into the circulation was restored back to basal level after long-term pegfilgrastim treatment in SOD1 mice while the storage of Ly6C expressing monocytes in the bone marrow and spleen remained elevated. After pegfilgrastim treatment, an increased proportion of these cells in the degenerative muscle was detected at the end stage of ALS. Conclusions GCSF attenuated inflammation in the CNS and the periphery in a mouse model of ALS and thereby delayed the progression of the disease. This mechanism of action targeting inflammation provides a new perspective of the usage of GCSF in the treatment of ALS.

  15. Chlamydia pneumoniae hides inside apoptotic neutrophils to silently infect and propagate in macrophages.

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    Jan Rupp

    Full Text Available BACKGROUND: Intracellular pathogens have developed elaborate strategies for silent infection of preferred host cells. Chlamydia pneumoniae is a common pathogen in acute infections of the respiratory tract (e.g. pneumonia and associated with chronic lung sequelae in adults and children. Within the lung, alveolar macrophages and polymorph nuclear neutrophils (PMN are the first line of defense against bacteria, but also preferred host phagocytes of chlamydiae. METHODOLOGY/PRINCIPAL FINDINGS: We could show that C. pneumoniae easily infect and hide inside neutrophil granulocytes until these cells become apoptotic and are subsequently taken up by macrophages. C. pneumoniae infection of macrophages via apoptotic PMN results in enhanced replicative activity of chlamydiae when compared to direct infection of macrophages, which results in persistence of the pathogen. Inhibition of the apoptotic recognition of C. pneumoniae infected PMN using PS- masking Annexin A5 significantly lowered the transmission of chlamydial infection to macrophages. Transfer of apoptotic C. pneumoniae infected PMN to macrophages resulted in an increased TGF-ss production, whereas direct infection of macrophages with chlamydiae was characterized by an enhanced TNF-alpha response. CONCLUSIONS/SIGNIFICANCE: Taken together, our data suggest that C. pneumoniae uses neutrophil granulocytes to be silently taken up by long-lived macrophages, which allows for efficient propagation and immune protection within the human host.

  16. Vector-borne pathogens in dogs from Costa Rica: first molecular description of Babesia vogeli and Hepatozoon canis infections with a high prevalence of monocytic ehrlichiosis and the manifestations of co-infection.

    Science.gov (United States)

    Rojas, Alicia; Rojas, Diana; Montenegro, Víctor; Gutiérrez, Ricardo; Yasur-Landau, Daniel; Baneth, Gad

    2014-01-31

    Infection with canine vector-borne pathogens was evaluated in dogs from four different regions of Costa Rica by PCR. Demographic data, clinical signs, packed cell volume values, and the presence of tick infestation were recorded for each dog. Forty seven percent (69/146) of the dogs were infected with at least one pathogen and 12% were co-infected with two pathogens. Ehrlichia canis was detected in 34%, Anaplasma platys in 10%, Babesia vogeli in 8%, and Hepatozoon canis in 7.5% of the blood samples. No infection was detected with Leishmania spp. in blood, skin scrapings or conjunctival swabs. Thirty percent of the dogs presented at least one clinical sign compatible with vector-borne disease, and of those, 66% were infected with a pathogen. Subclinical infections were determined in 58% of the infected dogs including 82% (9/11), 58% (29/50), 42% (5/12) and 36% (5/14) of the dogs with H. canis, E. canis, B. vogeli and A. platys infections, respectively. A distinct relationship was found between infection and anemia. The mean PCV values were 34.4% in dogs with no infection, 31.5% in those who had a single infection and 23% in those with co-infection. Co-infected dogs had significantly lower PCV values compared to non-infected and single-infected dogs (pcanis were significantly associated with R. sanguineus s.l. infestation (pcanis in Costa Rica as well as in Central America. The results of this study indicate that multiple vector-borne pathogens responsible for severe diseases infect dogs in Costa Rica and therefore, increased owner and veterinarian awareness are needed. Moreover, prevention of tick infestation is recommended to decrease the threat of these diseases to the canine population. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Correlation Between Serum Concentrations of N-Desmethylclozapine and Granulocyte Levels in Patients with Schizophrenia: A Retrospective Observational Study.

    Science.gov (United States)

    Smith, Robert L; Haslemo, Tore; Andreassen, Ole A; Eliasson, Erik; Dahl, Marja-Liisa; Spigset, Olav; Molden, Espen

    2017-11-01

    Clozapine is restricted to use in patients with treatment-refractory schizophrenia due to the risk of a serious drop in absolute neutrophil granulocyte count (ANC). The formation of reactive, unstable metabolites (adducts) has been suggested as a mechanism of clozapine-induced granulocyte decline. These adducts are not detectable in vivo, but stable clozapine metabolites could potentially be indirect pharmacokinetic measures of adduct formation. The present retrospective observational study investigated the correlation between concentrations of N-desmethylclozapine, the major stable clozapine metabolite, and ANC in a real-life population of clozapine-treated patients. Patients were included from a therapeutic drug monitoring service at the Center for Psychopharmacology, Diakonhjemmet Hospital, Oslo, Norway, between March 2005 and December 2015. Information about clozapine and N-desmethylclozapine steady-state trough concentrations, as well as accompanying measurements of ANC, were collected from the laboratory database. Correlations of serum concentrations of N-desmethylclozapine and clozapine (and their respective ratios) with ANC were investigated by linear mixed-model analysis. Overall, 129 patients with 855 measurements of clozapine/N-desmethylclozapine concentrations and ANC (range 0.9-19 × 10 9 cells/L, median 4.6) were included. Concentrations of N-desmethylclozapine, but not clozapine, correlated significantly and positively with ANC (estimated model slope 0.0011 × 10 9 cells/L/nM; p = 0.002), and the N-desmethylclozapine/clozapine ratio also positively correlated with ANC (p = 0.040). N-Desmethylclozapine level and ANC significantly correlated in this real-life population of schizophrenia patients. The positive correlation, which was also present for the metabolic ratio, might reflect reduced clozapine availability for the formation of reactive metabolites potentially affecting granulocyte level. However, as our findings were based on ANC mainly

  18. Modulation and Apoptosis of Neutrophil Granulocytes by Extracorporeal Photopheresis in the Treatment of Chronic Graft-Versus-Host Disease.

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    Cindy Franklin

    Full Text Available Chronic graft-versus-host disease (cGVHD is a common side effect of allogeneic stem cell transplantation and a major cause of morbidity and mortality in affected patients. Especially skin, eyes and oral mucosa are affected. This can lead to pain and functional impairment. Extracorporeal photopheresis (ECP is an effective immunomodulatory therapy with minimal side effects but its mode of action is still largely unknown. The objective of the present study was to examine the effects of ECP on neutrophil granulocytes in patients with cGVHD. Analysis of leukocytes from cGVHD patients obtained from the ECP device during treatment showed that neutrophil granulocytes account for the majority of cells treated during ECP. Neutrophils from healthy donors treated in vitro with 8-methoxypsoralen and UVA light as well as neutrophils from buffy coats of patients with cGVHD treated by ECP showed increased apoptosis and decreased half-life. In remaining non-apoptotic cells chemoirradiation resulted in loss of activation markers and reduced effector functions. This was accompanied by an increase in extracellular arginase-1 activity. Additional comparison of neutrophils isolated from blood of cGVHD patients before and 24h after ECP revealed a decreased half-life and reduction of effector functions of post-ECP neutrophils ex vivo. These observations strongly suggest that ECP induces both apoptosis and physiological changes in neutrophils and that these changes also take place in vivo. This study is the first to show that ECP modulates apoptosis and inflammatory activity in neutrophil granulocytes, indicating that neutrophils may significantly contribute to the overall immunomodulatory effects attributed to this treatment.

  19. Ehrlichiosis

    Science.gov (United States)

    ... Ehrlichia bacteria can be carried by the: American dog tick Deer tick ( Ixodes scapularis ), which can also ... your vital signs, including: Blood pressure Heart rate Temperature Other tests include: Complete blood count ( CBC ) Granulocyte ...

  20. Granulocyte-colony stimulating factor (G-CSF improves motor recovery in the rat impactor model for spinal cord injury.

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    Tanjew Dittgen

    Full Text Available Granulocyte-colony stimulating factor (G-CSF improves outcome after experimental SCI by counteracting apoptosis, and enhancing connectivity in the injured spinal cord. Previously we have employed the mouse hemisection SCI model and studied motor function after subcutaneous or transgenic delivery of the protein. To further broaden confidence in animal efficacy data we sought to determine efficacy in a different model and a different species. Here we investigated the effects of G-CSF in Wistar rats using the New York University Impactor. In this model, corroborating our previous data, rats treated subcutaneously with G-CSF over 2 weeks show significant improvement of motor function.

  1. Clinical outcome after stem cell mobilization with granulocyte-colony-stimulating factor after acute ST-elevation myocardial infarction:

    DEFF Research Database (Denmark)

    Ripa, Rasmus S; Jørgensen, Erik; Kastrup, Jens

    2013-01-01

    Background. Granulocyte-colony-stimulating factor (G-CSF) has been investigated in trials aiming to promote recovery of myocardial function after myocardial infarction. Long-term safety-data have never been reported. A few studies indicated an increased risk of in-stent re-stenosis. We aimed to i.......8; 0.3). Conclusions. We found no indication of increased risk of adverse events up to 5 years after G-CSF treatment. These results support the continued investigation of G-CSF for cardiac therapy....

  2. Isolation, nucleotide sequence and expression of a cDNA encoding feline granulocyte colony-stimulating factor.

    Science.gov (United States)

    Dunham, S P; Onions, D E

    2001-06-21

    A cDNA encoding feline granulocyte colony stimulating factor (fG-CSF) was cloned from alveolar macrophages using the reverse transcriptase-polymerase chain reaction. The cDNA is 949 bp in length and encodes a predicted mature protein of 174 amino acids. Recombinant fG-CSF was expressed as a glutathione S-transferase fusion and purified by affinity chromatography. Biological activity of the recombinant protein was demonstrated using the murine myeloblastic cell line GNFS-60, which showed an ED50 for fG-CSF of approximately 2 ng/ml. Copyright 2001 Academic Press.

  3. STUDIES IN DYNAMICS OF APOPTOSIS-RELATED SURFACE ANTIGEN (CD95 EXPRESSION ON NEUTROPHILS FROM CERVICAL AND VAGINAL SECRETIONS IN WOMEN WITH CHLAMIDIA INFECTION

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    O. A. Giesinger

    2010-01-01

    Full Text Available CD95 (Fas/APO-1 antigen expression was studied on the surface of neutrophil granulocytes from cervical secretions. Sixty-five female patients with established Chlamydia infection were found to have an increased CD95+ antigen expression following basic therapy. CD95+ receptors on neutrophils in the patients with Chlamydia infection have been shown to return to normal levels following a combined magnetic laser treatment.

  4. Ontogeny of the granulocyte/macrophage progenitor cell (GM-CFC) pools in the beagle.

    Science.gov (United States)

    Nothdurft, W; Braasch, E; Calvo, W; Prümmer, O; Carbonell, F; Grilli, G; Fliedner, T M

    1984-04-01

    The pattern of development of the granulocyte/macrophage progenitor cell (GM-CFC) pools in the course of canine ontogeny was studied by means of the agar culture technique. Colony formation was stimulated by colony stimulating activity (CSA) in serum from lethally irradiated dogs in combination with erythrocyte-depleted peripheral blood leukocytes from normal adult dogs. The colonies thus obtained in cultures from the different organs were in general large (estimated maximum 50 000 cells) and consisted predominantly of mononucleated macrophages, suggesting that, in these studies, a progenitor cell with high proliferative potential (HPP-CFC) has been monitored. In the yolk sac, a transitory GM-CFC pool became established between day 23 and day 48 of gestation, reaching maximum numbers of approximately 41 X 10(3) per organ on days 36/37. At the same time the GM-CFC concentration in blood collected from the heart also reached a maximum of about 31 X 10(3)/ml, indicating its carrier function for the migration of GM-CFC. In the liver a quasi-exponential increase in the GM-CFC numbers took place between days 36/37 and days 57 to 59 when a total of about 15.2 X 10(6) was found but thereafter and up to day 4 post partum the GM-CFC numbers decreased by almost two orders of magnitude. A continuous increase in the GM-CFC numbers was found in the spleen between day 42 of gestation and day 4 post partum when a maximum of 5.1 X 10(6) to 8.7 X 10(6) was reached. In contrast to the GM-CFC numbers in the liver, the splenic GM-CFC dropped only by 50% of peak values when the dogs reached adulthood. The bone marrow always had the highest incidence of GM-CFC, the concentration per 10(6) cells being 18.7 X 10(3)/10(6) cells on days 45/46, the earliest time point at which cultures could be set up. The absolute GM-CFC numbers in the two femora increased continuously between days 45/46 and day 4 post partum in parallel with the growth of the bones. In the thymus a relatively small

  5. Bone marrow immunoscintigraphy using technetium-99m anti-granulocyte antibody in multiple myeloma

    International Nuclear Information System (INIS)

    Sohn, Sang-Kyun; Kim, Dong-Hwan; Park, So-Hyang; Ahn, Byeong-Cheol; Lee, Sang-Woo; Chun, Kyung-Ah; Kim, Jung-Gyun; Lee, Kyu Bo; Lee, Jaetae; Song, Hong-Suk

    2002-01-01

    Conventional skeletal radiography and bone scan have certain limitations in the initial evaluation of bone and bone marrow lesions in multiple myeloma (MM). In this study we investigated the value of bone marrow immunoscintigraphy (BMIS) using anti-granulocyte monoclonal antibody (AGA) for the diagnosis of bone involvement of MM, in comparison with bone scan and skeletal radiography. Whole-body BMIS using technetium-99m-labelled AGA was performed in 22 MM patients (15 male, 7 female) and the imaging findings compared with those of skeletal radiography and 99m Tc-methylene diphosphonate bone scan. The findings of bone marrow aspiration and serum biochemical findings were also compared with BMIS findings. Abnormal findings of BMIS were defined as presence of a focal photon defect in the axial skeleton or expansion of peripheral bone marrow. A total of 124 focal lesions were detected in 19 subjects (86%) by skeletal radiography, bone scan or BMIS. BMIS detected 92 lesions (74%) in 19 subjects, whereas skeletal radiography detected 58 focal lesions (47%) in 14 and bone scan 40 lesions (32%) in 11. Fifty-one (41%) of the 124 lesions were only seen on BMIS. Spine and pelvic lesions were better visualised by BMIS, whereas skull lesions were better seen with skeletal radiography, and bone scan detected more lesions in the ribs. Marrow expansion was noted in 15 subjects (68%) on BMIS, and its grade correlated with marrow cellularity and myeloma cell percentage in bone marrow aspirates (P=0.0055 and P=0.0541, respectively). BMIS revealed abnormal lesions in one of three stage II patients and 17 out of 19 stage III patients. The number of lesions of the thoracolumbar vertebrae on BMIS was correlated with cellularity (P=0.0393), but not with myeloma cell percentage (P=0.1262). These findings suggest that the results of BMIS with 99m Tc-labelled AGA correlate with clinical stage, and thus reflect the functional status of bone marrow in MM patients. BMIS might be useful for the

  6. Regulation of wound healing by granulocyte-macrophage colony-stimulating factor after vocal fold injury.

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    Jae-Yol Lim

    Full Text Available OBJECTIVES: Vocal fold (VF scarring remains a therapeutic challenge. Granulocyte-macrophage colony-stimulating factor (GM-CSF facilitates epithelial wound healing, and recently, growth factor therapy has been applied to promote tissue repair. This study was undertaken to investigate the effect of GM-CSF on VF wound healing in vivo and in vitro. METHODS: VF scarring was induced in New Zealand white rabbits by direct injury. Immediately thereafter, either GM-CSF or PBS was injected into the VFs of rabbits. Endoscopic, histopathological, immunohistochemical, and biomechanical evaluations of VFs were performed at 3 months post-injury. Human vocal fold fibroblasts (hVFFs were cultured with GM-CSF. Production of type I and III collagen was examined immunocytochemically, and the synthesis of elastin and hyaluronic acids was evaluated by ELISA. The mRNA levels of genes related to ECM components and ECM production-related growth factors, such as HGF and TGF-ß1, were examined by real time RT-PCR. RESULTS: The GM-CSF-treated VFs showed reduced collagen deposition in comparison to the PBS-injected controls (P<0.05. Immunohistochemical staining revealed lower amounts of type I collagen and fibronectin in the GM-CSF-treated VFs (P<0.05 and P<0.01, respectively. Viscous and elastic shear moduli of VF samples were significantly lower in the GM-CSF group than in the PBS-injected group (P<0.001 and P<0.01, respectively. Mucosal waves in the GM-CSF group showed significant improvement when compared to the PBS group (P = 0.0446. GM-CSF inhibited TGF-β1-induced collagen synthesis by hVFFs (P<0.05 and the production of hyaluronic acids increased at 72 hours post-treatment (P<0.05. The expressions of HAS-2, tropoelastin, MMP-1, HGF, and c-Met mRNA were significantly increased by GM-CSF, although at different time points (P<0.05. CONCLUSION: The present study shows that GM-CSF offers therapeutic potential for the remodeling of VF wounds and the promotion of VF

  7. Comparison of two strategies for the treatment of radiogenic leukopenia using granulocyte colony stimulating factor

    International Nuclear Information System (INIS)

    Adamietz, I.A.; Rosskopf, B.; Dapper, F.D.; Lieven, H. von; Boettcher, H.D.

    1996-01-01

    Purpose: Radiation-induced leukopenia can cause a delay or discontinuation of radiotherapy. This complication can be overcome with the use of granulocyte colony-stimulating factor (G-CSF). However, an uncertainty exists regarding the mode of application of G-CSF in patients treated with radiotherapy. For this reason, the efficacy of two strategies for the administration of G-CSF in irradiated patients was compared in a prospective randomized clinical study. Methods and Materials: Forty-one patients who developed leukopenia ( 9 per liter) while undergoing radiotherapy were treated with G-CSF at a daily dose of 5 μg/kg. The first group received single injections of G-CSF as required (n = 21). The second group received G-CSF on at least 3 consecutive days (n = 20). An analysis was made of the changes in leucocyte counts, the number of days on which radiotherapy had to be interrupted, and the side effects of growth-factor treatment. Results: An increase in leucocyte values in the peripheral blood was observed in all patients treated with G-CSF. In the group which received G-CSF when required, two injections (range: 1-8) were administered in most cases. In the second group, most of the patients received three injections (range: 3-9). The average duration of therapy interruptions due to leukopenia was 4.8 days (0-28) in the first therapy arm and 2.5 (0-20) in the second arm. The variance in the duration of therapy interruptions between the two groups was not significant (p = 0.2). Radiotherapy had to be terminated in two patients due to thrombocytopenia but the application of G-CSF did not seem to be a reason of decreasing platelet counts. Conclusions: Our results reveal that G-CSF is safe and effective in the treatment of radiation-induced leukopenia regardless of the mode of application. Because the calculated difference related to radiation treatment interruptions has no clinical relevance, both approaches examined in our study appear reasonable.

  8. CXCL1 can be regulated by IL-6 and promotes granulocyte adhesion to brain capillaries during bacterial toxin exposure and encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Roy Monica

    2012-01-01

    Full Text Available Abstract Background Granulocytes generally exert protective roles in the central nervous system (CNS, but recent studies suggest that they can be detrimental in experimental autoimmune encephalomyelitis (EAE, the most common model of multiple sclerosis. While the cytokines and adhesion molecules involved in granulocyte adhesion to the brain vasculature have started to be elucidated, the required chemokines remain undetermined. Methods CXCR2 ligand expression was examined in the CNS of mice suffering from EAE or exposed to bacterial toxins by quantitative RT-PCR and in situ hybridization. CXCL1 expression was analyzed in IL-6-treated endothelial cell cultures by quantitative RT-PCR and ELISA. Granulocytes were counted in the brain vasculature after treatment with a neutralizing anti-CXCL1 antibody using stereological techniques. Results CXCL1 was the most highly expressed ligand of the granulocyte receptor CXCR2 in the CNS of mice subjected to EAE or infused with lipopolysaccharide (LPS or pertussis toxin (PTX, the latter being commonly used to induce EAE. IL-6 upregulated CXCL1 expression in brain endothelial cells by acting transcriptionally and mediated the stimulatory effect of PTX on CXCL1 expression. The anti-CXCL1 antibody reduced granulocyte adhesion to brain capillaries in the three conditions under study. Importantly, it attenuated EAE severity when given daily for a week during the effector phase of the disease. Conclusions This study identifies CXCL1 not only as a key regulator of granulocyte recruitment into the CNS, but also as a new potential target for the treatment of neuroinflammatory diseases such as multiple sclerosis.

  9. Thermo-radiosensitivity of the granulocyte and macrophage precursor cells of mice. II. - X irradiation effects and influence of hyperthermia on the radiosensitivity

    International Nuclear Information System (INIS)

    Bueren, J.A.; Nieto, M.

    1983-01-01

    The effects of the X-irradiation on the viability of the granulocyte-macrophage precursors, has been determined by means of the agar diffusion chamber culture technique. The results show the high radiosensitivity of these cells, with survival parameter similar to those previously reported in the literature about different granulocyte-macrophage precursors. When a hyperthermic treatment is performed prior to the X-irradiation, a radiosensitization phenomenon is observed due to the synergism existent between hyperthermia and X rays on the lethality of the precursors. (Authors) 37 refs

  10. Infliximab- and Immunosuppressant-Resistant Crohn’s Disease Successfully Treated with Adsorptive Granulocyte Apheresis Combined with Prednisolone

    Directory of Open Access Journals (Sweden)

    Munenori Itagaki

    2012-02-01

    Full Text Available Activated granulocytes, monocytes, and platelets appear to be closely involved in active Crohn’s disease (CD. Adsorptive granulocyte apheresis (GCAP is a new treatment for inflammatory bowel disease. GCAP was used to treat a 23-year-old female patient with CD resistant to both infliximab (IFX and azathioprine (AZA. At 16 years of age, the patient underwent a partial ileal resection for peritonitis caused by perforative ileitis. On pathological examination of the resected specimen, the diagnosis was CD. Mesalazine was started, but the patient did not comply with therapy. She was admitted to our hospital again in 2007 due to an acute exacerbation. IFX induction therapy was started. The combination of both AZA daily and IFX every 8 weeks was continued as maintenance therapy. However, she developed severe abdominal pain in September 2009. Computed tomography revealed ileitis and ascending colitis, and blood tests showed high inflammatory response marker levels. She was considered to have IFX- and AZA-resistant CD. Initial intravenous steroid therapy did not result in any improvement. Therefore, weekly GCAP therapy was given for 5 weeks, which immediately improved the inflammatory response markers. GCAP combined with prednisolone could be effective for IFX- and AZA-refractory CD.

  11. Evaluation of haemato-biochemical and oxidative indices in naturally infected concomitant tick borne intracellular diseases in dogs

    Directory of Open Access Journals (Sweden)

    Kalyan Sarma

    2015-01-01

    Full Text Available Objective: To explore haemato-biochemical and oxidative stress indices due to concomitant tick borne intracellular diseases in dogs presented at Referral Veterinary Polyclinic, Indian Veterinary Research Institute, Bareilly during May 2010 to May 2012. Methods: Microscopy of Giemsa blood smear and ELISA test (SNAP 4D伊 were carried out in suspected cases to confirm haemo-parasitic infection. Blood and serum samples were analyzed for oxidative stress indices and haemato-biochemical changes. All the ailing conditions were recorded to investigate the clinical pattern of concomitant tick borne diseases. Ultrasonographic study was carried out to obtain the hepatic involvement. Results: Examination of 3 650 dogs revealed that 2.77% dog were positive for various tick borne diseases, out of which 21.78% were with concomitant infection. Clinical symptoms were noted with overall mean clinical score of 9.95依0.30. Ultrasonographic examination revealed hepatomegaly, distension of gall bladder, and ascites. Haemato-biochemical evaluation confirmed anaemia, leucopenia, thrombocytopenia, hypoproteinemia, hypoalbuminemia, hyperglobulinemia and hyperbilirubinemia with increased serum alanine amino transferase, alkaline phosphatase and gamma-glutamyl transpeptidase in concomitant infected dogs. The lipid peroxidation level of concomitant infection was significantly higher (P<0.05 than healthy group whereas superoxide dismutase, glutathione-reduced and catalase activity in concomitant infected group were decreased. Conclusions: The severity of infection was more pronounced in dogs harboring Ehrlichia, Babesia and Hepatozoon and the oxidative stress may have a pathophysiological role in concomitant infection in dogs.

  12. The effect of granulocyte-colony stimulating factor on rotator cuff healing after injury and repair.

    Science.gov (United States)

    Ross, David; Maerz, Tristan; Kurdziel, Michael; Hein, Joel; Doshi, Shashin; Bedi, Asheesh; Anderson, Kyle; Baker, Kevin

    2015-05-01

    The failure rate of tendon-bone healing after repair of rotator cuff tears remains high. A variety of biologic- and cell-based therapies aimed at improving rotator cuff healing have been investigated, and stem cell-based techniques have become increasingly more common. However, most studies have focused on the implantation of exogenous cells, which introduces higher risk and cost. We aimed to improve rotator cuff healing by inducing endogenous stem cell mobilization with systemic administration of granulocyte-colony stimulating factor (G-CSF). We asked: (1) Does G-CSF administration increase local cellularity after acute rotator cuff repair? (2) Is there histologic evidence that G-CSF improved organization at the healing enthesis? (3) Does G-CSF administration improve biomechanical properties of the healing supraspinatus tendon-bone complex? (4) Are there micro-MRI-based observations indicating G-CSF-augmented tendon-bone healing? After creation of full-thickness supraspinatus tendon defects with immediate repair, 52 rats were randomized to control or G-CSF-treated groups. G-CSF was administered for 5 days after repair and rats were euthanized at 12 or 19 postoperative days. Shoulders were subjected to micro-MR imaging, stress relaxation, and load-to-failure as well as blinded histologic and histomorphometric analyses. G-CSF-treated animals had significantly higher cellularity composite scores at 12 and 19 days compared with both control (12 days: 7.40 ± 1.14 [confidence interval {CI}, 5.98-8.81] versus 4.50 ± 0.57 [CI, 3.58-5.41], p = 0.038; 19 days: 8.00 ± 1.00 [CI, 6.75-9.24] versus 5.40 ± 0.89 [CI, 4.28-6.51], p = 0.023) and normal animals (12 days: p = 0.029; 19 days: p = 0.019). There was no significant difference between G-CSF-treated animals or control animals in ultimate stress (MPa) and strain, modulus (MPa), or yield stress (MPa) and strain at either 12 days (p = 1.000, p = 0.104, p = 1.000, p = 0.909, and p = 0.483, respectively) or 19 days (p = 0

  13. Infection by Mycoplasma spp., feline immunodeficiency virus and feline leukemia virus in cats from an area endemic for visceral leishmaniasis.

    Science.gov (United States)

    Marcondes, Mary; Hirata, Karina Y; Vides, Juliana P; Sobrinho, Ludmila S V; Azevedo, Jaqueline S; Vieira, Thállitha S W J; Vieira, Rafael F C

    2018-03-20

    Visceral leishmaniasis (VL) has been increasingly recognized in cats living in areas endemic for the disease. Co-infection with Leishmania infantum and other infectious agents is well established in dogs. However, for cats, data on co-infections with L. infantum and other infectious agents are still sparse. The aim of this study was to identify the prevalence of vector-borne pathogens, Mycoplasma spp., feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) in cats from an area endemic for VL in southeastern Brazil. Of the 90 cats, eight (8.9%) were infected with Mycoplasma spp., five (5.5%) were FIV- positive and one (1.1%) was FeLV-positive. Co-infection with L. infantum and at least one other infectious agent was found in 9/50 (18.0%; CI: 8.6-31.4%) cats. In Group 1 (cats infected naturally by L. infantum), 4/50 (8.0%) cats were positive for FIV, 4/50 (8%) for Mycoplasma spp. and 1/50 (2.0%) was co-infected with FeLV and Mycoplasma spp. In Group 2 (cats non-infected with L. infantum), 2/40 (5.0%) cats were infected with Mycoplasma spp. and 1/40 (2.5%) was co-infected with FIV and Mycoplasma spp. All cats were negative for Ehrlichia spp., Babesia spp. and Anaplasma platys. A low prevalence of co-infection in Leishmania-infected and non-infected cats was found. Co-infections with Leishmania and vector-borne diseases in cats are not common in this area endemic for VL in Brazil.

  14. Primary granulocyte colony-stimulating factor prophylaxis during the first two cycles only or throughout all chemotherapy cycles in patients with breast cancer at risk for febrile neutropenia

    NARCIS (Netherlands)

    Aarts, M.J.; Peters, F.P.; Mandigers, C.M.P.W.; Dercksen, M.W.; Stouthard, J.M.; Nortier, H.J.; Laarhoven, H.W.M. van; Warmerdam, L.J. van; Wouw, A.J. van de; Jacobs, E.M.G.; Mattijssen, V.; Rijt, C.C. van der; Smilde, T.J.; Velden, A.W. van der; Temizkan, M.; Batman, E.; Muller, E.W.; Gastel, S.M. van; Borm, G.F.; Tjan-Heijnen, V.C.

    2013-01-01

    PURPOSE: Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF

  15. Primary Granulocyte Colony-Stimulating Factor Prophylaxis During the First Two Cycles Only or Throughout All Chemotherapy Cycles in Patients With Breast Cancer at Risk for Febrile Neutropenia

    NARCIS (Netherlands)

    Aarts, Maureen J.; Peters, Frank P.; Mandigers, Caroline M.; Dercksen, M. Wouter; Stouthard, Jacqueline M.; Nortier, Hans J.; van Laarhoven, Hanneke W.; van Warmerdam, Laurence J.; van de Wouw, Agnes J.; Jacobs, Esther M.; Mattijssen, Vera; van der Rijt, Carin C.; Smilde, Tineke J.; van der Velden, Annette W.; Temizkan, Mehmet; Batman, Erdogan; Muller, Erik W.; van Gastel, Saskia M.; Borm, George F.; Tjan-Heijnen, Vivianne C. G.

    2013-01-01

    Purpose Early breast cancer is commonly treated with anthracyclines and taxanes. However, combining these drugs increases the risk of myelotoxicity and may require granulocyte colony-stimulating factor (G-CSF) support. The highest incidence of febrile neutropenia (FN) and largest benefit of G-CSF

  16. Dose intensity of standard adjuvant CMF with granulocyte colony-stimulating factor for premenopausal patients with node-positive breast cancer

    NARCIS (Netherlands)

    deGraaf, H; Willemse, PHB; Bong, SB; Piersma, H; Tjabbes, T; vanVeelen, H; Coenen, JLLM; deVries, EGE

    1996-01-01

    The effects of granulocyte colony-stimulating factor (G-CSF) on total dose and dose intensity of standard oral adjuvant CMF (cyclophosphamide, methotrexate, and 5-fluorouracil) chemotherapy were studied in premenopausal patients with node-positive breast cancer. Treatment consisted of standard CMF

  17. Effects of recombinant human granulocyte colony-stimulating factor on leucopenia in zidovudine-treated patients with AIDS and AIDS related complex, a phase I/II study

    NARCIS (Netherlands)

    van der Wouw, P. A.; van Leeuwen, R.; van Oers, R. H.; Lange, J. M.; Danner, S. A.

    1991-01-01

    Twelve male patients, eight with the acquired immunodeficiency syndrome (AIDS) and four with AIDS related complex (ARC), who had zidovudine associated neutropenia (less than 1 x 10(9) neutrophils/l) were treated with recombinant human granulocyte colony-stimulating factor (G-CSF) in a phase I/II

  18. Functional and molecular evidence for heteromeric association of P2Y1 receptor with P2Y2 and P2Y4 receptors in mouse granulocytes.

    Science.gov (United States)

    Ribeiro-Filho, Antonio Carlos; Buri, Marcus Vinicius; Barros, Carlos Castilho; Dreyfuss, Juliana Luporini; Nader, Helena Bonciani; Justo, Giselle Zenker; Craveiro, Rogério Bastos; Pesquero, João Bosco; Miranda, Antonio; Ferreira, Alice Teixeira; Paredes-Gamero, Edgar Julian

    2016-07-07

    All hematopoietic cells express P2 receptors, however pharmacological characteristics such as expression and affinity in granulocytes are unknown. Pharmacological characteristics of P2 receptors were evaluated by Ca(2+) measurements using Fura-2 fluorophore. P2 receptors expression were analyzed by flow cytometry and RT-PCR. P2 interaction were shown by coimmunoprecipitation, western blotting and FRET. Granulocytes were responsive to P2Y agonists, whereas P2X agonists were ineffective. Ca(2+) increase, elicited by ADP and UTP was dependent on intracellular stocks and sensitive to G-coupled receptor inhibition. Moreover, MRS2179, a specific antagonist of the P2Y1 receptor, abolished ADP response. Interestingly, ADP and UTP exhibited full heterologous desensitization, suggesting that these agonists interact with the same receptor. The heteromeric association between P2Y1 receptor and the P2Y2 and P2Y4 receptors was shown by immunoprecipitation and FRET analysis. Clear evidence of heteromeric association of P2Y receptors was found during the evaluation of P2 receptors present in mice granulocytes, which could impact in the classical pharmacology of P2Y receptors in granulocytes.

  19. Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice

    Energy Technology Data Exchange (ETDEWEB)

    Kabaya, Koji; Watanabe, Masahiko; Kusaka, Masaru; Seki, Masatoshi (Kirin Brewery Co., Ltd., Gunma (Japan). Pharmaceutical Research Laboratory); Fushiki, Masato

    1994-08-01

    The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 [mu]g/body/day from day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also reveals an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation. (author).

  20. Promotive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on recovery from neutropenia induced by fractionated irradiation in mice

    International Nuclear Information System (INIS)

    Kabaya, Koji; Watanabe, Masahiko; Kusaka, Masaru; Seki, Masatoshi; Fushiki, Masato.

    1994-01-01

    The effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on the recovery from neutropenia induced by fractionated whole-body irradiation was investigated in mice. Male 7-week old C3H/HeN mice received a total of ten exposures of 0.25 Gy/day from day 1 to 5 and from day 8 to 12. Peripheral neutropenia with a nadir on day 17 was caused by the fractionated irradiation. Daily subcutaneous injections of rhG-CSF at 0.25 and 2.5 μg/body/day from day from day 1 to 21 promoted the recovery of neutrophils in a dose-dependent manner. The kinetics of morphologically identifiable bone marrow cells were studied to clarify the mechanism behind the promotive effect of this factor. A slight decrease in mitotic immature granulocytes, such as myeloblasts, promyelocytes and myelocytes on day 5, and a drastic decrease in metamyelocytes and marrow neutrophils on days 5, 9, and 17 were seen in the femur of irradiated mice. Treatment using rhG-CSF caused an increase in immature granulocytes of all differential stages in the femur. Microscopic findings of the femurs and spleens also reveals an increase in immature granulocytes in these organs in mice injected with rhG-CSF. These results indicate that rhG-CSF accelerates granulopoiesis in the femur and spleen, thereby promoting recovery from neutropenia induced by fractionated irradiation. (author)

  1. Ovarian granulocytic sarcoma: a case report and magnetic resonance imaging findings; Sarcoma granulocitico no ovario: relato de caso e achados na ressonancia magnetica

    Energy Technology Data Exchange (ETDEWEB)

    Pereira, Licia Pacheco [Hospital Geral de Fortaleza (HGF), CE (Brazil). Servico de Diagnostico por Imagem], e-mail: licia_p@hotmail.com; Silveira, Claudio Regis Sampaio [Hospital Geral de Fortaleza (HGF), CE (Brazil). Servico de Radiologia; Costa, Fabricio da Silva [Universidade Estadual do Ceara (UECE), CE (Brazil); Monte, Hipolito [Hospital Monte Klinikum, Fortaleza, CE (Brazil)

    2008-12-15

    Granulocytic sarcoma (chloroma) is a tumor consisting of myeloid precursors in an extramedullary site. It is complication of both acute and chronic myelogenous leukemias. Although the lesion can occur at any site, ovarian involvement is rare. We report a case of ovary tumor associated with acute myeloid leukaemia and its imaging appearance on magnetic resonance. (author)

  2. Porcine granulocyte-colony stimulating factor (G-CSF) delivered via replication-defective adenovirus induces a sustained increase in circulating peripheral blood neutrophils

    Science.gov (United States)

    The use of immunomodulators is a promising area for biotherapeutic, prophylactic, and metaphylactic use to prevent and combat infectious disease, particularly during periods of peak disease incidence. Cytokines, including granulocyte colony-stimulating factor (G-CSF), are one class of compounds that...

  3. First case of Anaplasma platys infection in a dog from Croatia

    Directory of Open Access Journals (Sweden)

    Dyachenko Viktor

    2012-03-01

    Full Text Available Abstract Background It is known that Anaplasma (A. platys, the causative agent of infectious canine cyclic thrombocytopenia, is endemic in countries of the Mediterranean basin. However, few reports are available from the Balkans. This case report describes a dog, which was imported from Croatia to Germany in May 2010. One month later the dog was presented to a local veterinarian in Germany due to intermittent/recurrent diarrhoea. Diagnostic tests were performed to identify infections caused by Anaplasma spp., Ehrlichia spp., Hepatozoon canis, Babesia spp., Leishmania spp., Borrelia burgdorferi and/or Dirofilaria immitis. Findings Haematological examination of a blood smear revealed basophilic inclusions in thrombocytes, which were confirmed as A. platys with a species-specific real-time PCR. Additionally, an infection with Babesia (B. vogeli was also detected (PCR and serology. No specific antibodies against Anaplasma antigen were detectable. Although the dog showed no specific clinical signs, thrombocytopenia, anaemia and elevated C-reactive protein (CRP were observed. Sequencing of a 1,348-bp partial ribosomal RNA gene revealed highest homology to A. platys sequences from Thailand, Japan and France. Conclusions A. platys was detected for first time in a dog imported from Croatia. As the dog was also co-infected by B. vogeli, unique serological and haematological findings were recorded. Thrombocytopenia, anaemia and elevated values of C-reactive protein were the laboratory test abnormalities observed in this case. A. platys infections should be considered in dogs coming from Croatia and adjacent regions.

  4. Infection diagnosis in nuclear medicine

    International Nuclear Information System (INIS)

    Martin-Comin, J.

    1997-01-01

    Full text. The clinical applicability of agents like 67 Ga and 111 In-labelled leukocytes began the era of infection imaging diagnosis in Nuclear Medicine, more than two decades ago. In this period other agents have appeared in the field. 99 m Tc-HMPAQ-leukocytes and 99 m Tc-anti granulocyte monoclonal antibodies (able to label white blood cells) and 111 In and 99 mTc-polyclonal immuno globulins (in cold kit presentation). These agents had widespread the use of Nuclear Medicine procedures in clinical practice. Nevertheless, there is not, up to now, an specific agent to diagnose infection and is some cases a second or third agent (i.e.: 99 mTc-colloid) is used to obtain an accurate diagnosis. Actually, research is orientated to the development of agents with low antigenic power (peptides or fragments of monoclonal antibodies), or other non immunogenic agents involved in the inflammation process (selectin, antibiotic). Some experiences have also been done with PET agents. The clinical usefulness of commercially available agents and the future possibilities of the new ones will be presented

  5. Labeling of antibiotics for infection diagnosis

    International Nuclear Information System (INIS)

    Benitez, A.; Roca, M.; Martin-Comin, J.

    2006-01-01

    The high impact of infection on daily clinical practice has promoted research into better and more accurate diagnostic and therapeutic methods. Localizing inflammation/infection with nuclear medicine techniques began over 40 years ago. Today, 6 7G a-scintigraphy, 9 9mT c-nanocolloid, 1 11I n and 9 9mT c in vitro labeled leukocytes, and monoclonal anti granulocyte antibodies are widely available for this purpose. While these methods are useful for localizing inflammation, they cannot always differentiate septic from aseptic processes. The ideal properties of an agent for diagnosing infection include: high specificity, early diagnosis, rapid blood clearance, ease of preparation, low toxicity, biodistribution appropriate for the disease under study, absence of immunologic response and low cost. A novel approach to infection diagnosis is the use of radiolabelled antibiotics. Antibiotics localize in the infectious focus, where they are frequently taken up and metabolized by microorganisms. The majority of the various antibiotics studied so far are those of the quinolones group (ciprofloxacin, sparfloxacin, enrofloxacin, levofloxacin, norfloxacin and ofloxacin). More recently, the labeling of ceftizoxime, a semisynthetic third generation cephalosporin, has been reported. The relevant features of labeled antibiotics in research and/or clinical infection diagnosis are the focus of this article

  6. Effect of intravenous plasma transfusion on granulocyte and monocyte oxidative and phagocytic activity in dairy calves with failure of passive immunity.

    Science.gov (United States)

    Yang, Victoria C; Rayburn, Maire C; Chigerwe, Munashe

    2017-12-01

    Plasma administration has been recommended in calves older than 48h with failure of passive immunity (FPI) to provide immunity consistent with adequate colostral ingestion. However, the protective serum immunoglobulin G (IgG) concentrations (≥1000mg/dL) of plasma derived IgG only lasts up to 12h. In addition to IgG, maternally derived colostral cells also confer immunity. The objective of the study was to determine the effect of intravenous plasma transfusion on granulocyte and monocyte oxidative and phagocytic activity in calves with FPI. Twenty-seven, one day-old, Jersey calves were assigned into 3 groups. The colostral (CL, N=9) group received 3L of colostrum once by oroesophageal tubing. Two other groups of calves received 1L of colostrum once by oroesophageal tubing and were assigned based on their health status (sick or non-sick) at 4days of age, as the sick-group (SG, N=7) or the non-sick (NG, N=11) groups. At 4days of age, the SG and NG groups were administered plasma intravenously at 30mL/kg. Granulocyte and monocyte oxidative and phagocytic activity was determined by flow cytometry. There was no significant difference in the granulocyte and monocyte oxidative or phagocytic activity among the 3 groups (P>0.05). Plasma administration had no significant effect on the oxidative or phagocytic activity of granulocytes or monocytes. In clinical practice, plasma administration for enhancing oxidative or phagocytic activity of granulocytes or monocytes, alone, might not be justified in calves with FPI. Copyright © 2017 Elsevier Ltd. All rights reserved.

  7. Application of microchip CGE for the analysis of PEG-modified recombinant human granulocyte-colony stimulating factors.

    Science.gov (United States)

    Park, Eun Ji; Lee, Kyung Soo; Lee, Kang Choon; Na, Dong Hee

    2010-11-01

    The purpose of this study was to evaluate the microchip CGE (MCGE) for the analysis of PEG-modified granulocyte-colony stimulating factor (PEG-G-CSF) prepared with PEG-aldehydes. The unmodified and PEG-modified G-CSFs were analyzed by Protein 80 and 230 Labchips on the Agilent 2100 Bioanalyzer. The MCGE allowed size-based separation and quantitation of PEG-G-CSF. The Protein 80 Labchip was useful for PEG-5K-G-CSF, while the Protein 230 Labchip was more suitable for PEG-20K-G-CSF. The MCGE was also used to monitor a search for optimal PEG-modification (PEGylation) conditions to produce mono-PEG-G-CSF. This study demonstrates the usefulness of MCGE for monitoring and optimizing the PEGylation of G-CSF with the advantages of speed, minimal sample consumption, and automatic quantitation.

  8. Immunomodulatory effects of testosterone evaluated in all-trans retinoic acid differentiated HL-60 cells, granulocytes, and monocytes

    DEFF Research Database (Denmark)

    Boje, Alex; Moesby, Lise; Timm, Michael

    2012-01-01

    The sex hormones are known to affect innate immunity in humans. In this study we evaluated the immunomodulatory effects of testosterone in a model system comprising of all-trans retinoic acid differentiated HL-60 cells, and confirmed the results in human granulocytes and monocytes. Results showed...... that testosterone at pharmacological doses reduced the production of interleukin-8 and reactive oxygen species from differentiated HL-60 cells in a concentration dependent manner without affecting phagocytosis. The cells were stimulated with zymosan, lipopolysaccharide, or Bacillus subtilis. At the highest...... concentration of testosterone (120 µM), interleukin-8 secretion was reduced 42-80%, and production of reactive oxygen species was reduced 32-46%. Flutamide, an antagonist of the classical intracellular androgen receptor, was unable to antagonize the immunosuppressive effect of testosterone. We further...

  9. Presence of anti-Toxoplasma gondii, -Neospora caninum, -Leishmania spp. and -Ehrlichia canis antibodies in free-ranging maned wolves (Chrysocyon brachyurus in the northeastern region of the state of São Paulo, Brazil

    Directory of Open Access Journals (Sweden)

    Solange Oliveira

    2016-09-01

    Full Text Available O lobo-guará (Chrysocyon brachyurus habita o ecossistema de Cerrado e é considerado o maior canídeo da América do Sul e uma espécie ameaçada de extinção pela "International Union for Conservation of Nature" (IUNC. O objetivo desse estudo foi investigar a presença de anticorpos anti-Toxoplasma gondii, -Neospora caninum, -Leishmania spp. e -Ehrlichia canis em lobos-guará da região nordeste do estado de São Paulo, Brasil. Das 17 amostras de soro testadas por meio da reação de imunofluorescência indireta (RIFI, 88,2% (15/17, 17,6% (3/17 e 52,9% (9/17 apresentaram anticorpos anti-T. gondii, -Leishmania spp. e -E. canis, respectivamente. Todos os animais testados foram soronegativos para N. caninum. Esses resultados indicam a exposição dos lobos-guará dessa região aos agentes pesquisados. A presença de um complexo industrial, agricultura extensiva e fragmentação de habitat na região nordeste do estado de São Paulo, favorece a proximidade desses animais silvestres a ambientes urbanos o que pode contribuir para a transmissão de doenças entre os animais silvestres, domésticos e o homem.

  10. FEATURES OF CHEMILUMINESCENT ACTIVITY OF NEUTROPHILIC GRANULOCYTES IN PATIENTS WITH CHRONIC GASTRITIS, CHRONIC ATROPHIC GASTRITIS AND GASTRIC CANCER

    Directory of Open Access Journals (Sweden)

    O. V. Smirnova

    2017-01-01

    Full Text Available Chronic gastritis is the most common disease of gastro-intestinal tract. Precancerous potential is among most important epidemiological features of chronic gastritis. Immune system plays a distinct role in transformation from precancerous state to malignancy. In this context, the aim of our work was a study of spontaneous and induced chemiluminescence activity of neutrophilic granulocytes in patients with chronic superficial gastritis, chronic atrophic gastritis and gastric cancer. The work presents results of comprehensive laboratory examination of patients with chronic gastritis (CG (a total of 85 persons. 25 patients with chronic atrophic gastritis (CAG, and 50 patients with gastric cancer (GC at the age of 19 to 70 years were enrolled. Control group included 115 healthy donors without gastrointestinal complaints at the age of 19 to 67 years. The study was performed with venous blood samples taken from cubital vein into Vacutainer tubes with sodium heparin (5 U/mL prior to starting any pathogenic treatment. Evaluation of spontaneous and induced chemiluminescence was performed for 90 minutes at a 36-channel “CL 3606” chemiluminescence analyzer (Russia. In our study, patients with gastric cancer showed clear unidirectional changes in chemiluminescent activity of neutrophilic granulocytes (NG. When measuring spontaneous and induced NG chemiluminescence, we diagnosed a decreased phagocytic activity characterized by prolonged time-to-peak and area under the curve for spontaneous and induced CL, thus presuming longer activation time required in cases of reduced phagocytic function. The NG activity in patients with chronic gastritis is not impaired, but, similar changes of time-to-peak and area under were detected. Chemiluminescent activity of NG is increased in the group of CAG patients, and, considering similar changes in activation time and area under the curve, NG also produce greater amount of reactive oxygen species. Thus, for all H

  11. Influence of neutrophile granulocyte/lymphocyte ratio (NLR on poor prognosis of elderly AECOPD patients during hospital stay

    Directory of Open Access Journals (Sweden)

    Jian-Rong Cui

    2016-01-01

    Full Text Available Objective: To discuss the influence of neutrophile granulocyte/lymphocyte ratio(NLR to the poor prognosis of elderly AECOPD patients during the stay in hospital. Method: A total of 133 cases elderly patients with AECOPD admitted in our hospital from March 2013 to September 2014 were selected, and divided them into death group (31 cases and survival group (102 cases according to in-hospital death occurrence; To compare the on admission general clinical data, therapy method, lung function, blood routine examination [white blood cell count (WBC, neutrophile granulocyte/lymphocyte ratio(NLR], C-reactive protein (CRP, blood gas analysis and blood biochemical indexes in both groups, and drew ROC curve for a analysis of the clinical value of NLR in the prediction of death. Results: Among 133 cases of elderly AECOPD patients: the proportion of combined pulmonary heart disease and mechanical ventilation in death group was higher than that in survival group, PaCO2, WBC count, neutrophil count, NLR, CRP level in death group was higher, but lymphocyte count, serum albumin(ALB in death group was lower; multiple logistic regression analysis showed that NLR presented independent positive correlation with the in-hospital death in elderly AECOPD patients; ROC curve analysis showed that the ROCAUC of NLR to the inhospital death in elderly AECOPD patients was 0.787, the best diagnostic node value was 7.3, sensitivity and specificity were 77.4% and 74.5% respectively; bounded by NLR(7.3, divided patients into NLR≥7.3 group and NLR<7.3 group, hospital stays, CRP level and mortality in NLR≥7.3 group were higher than that in NLR<7.3 group. Conclusion: NLR was the high risk factor of the in-hospital death in elderly AECOPD patients, early detection of NLR level had a certain difference to the evaluation for short-term prognosis of elderly AECOPD patients and guide treatment.

  12. Granulocyte-Colony Stimulating Factor Receptor, Tissue Factor, and VEGF-R Bound VEGF in Human Breast Cancer In Loco.

    Science.gov (United States)

    Wojtukiewicz, Marek Z; Sierko, Ewa; Skalij, Piotr; Kamińska, Magda; Zimnoch, Lech; Brekken, Ralf A; Thorpe, Philip E

    2016-01-01

    Doxorubicin and docetaxel-based chemotherapy regimens used in breast cancer patients are associated with high risk of febrile neutropenia (FN). Granulocyte colony-stimulating factors (G-CSF) are recommended for both treating and preventing chemotherapy-induced neutropenia. Increased thrombosis incidence in G-CSF treated patients was reported; however, the underlying mechanisms remain unclear. The principal activator of blood coagulation in cancer is tissue factor (TF). It additionally contributes to cancer progression and stimulates angiogenesis. The main proangiogenic factor is vascular endothelial growth factor (VEGF). The aim of the study was to evaluate granulocyte-colony stimulating factor receptor (G-CSFR), tissue factor (TF) expression and vascular endothelial growth factor receptor (VEGF-R) bound VEGF in human breast cancer in loco. G-CSFR, TF and VEGFR bound VEGF (VEGF: VEGFR) were assessed in 28 breast cancer tissue samples. Immunohistochemical (IHC) methodologies according to ABC technique and double staining IHC procedure were employed utilizing antibodies against G-CSFR, TF and VEGF associated with VEGFR (VEGF: VEGFR). Expression of G-CSFR was demonstrated in 20 breast cancer tissue specimens (71%). In 6 cases (21%) the expression was strong (IRS 9-12). Strong expression of TF was observed in all investigated cases (100%). Moreover, expression of VEGF: VEGFR was visualized in cancer cells (IRS 5-8). No presence of G-CSFR, TF or VEGF: VEGFR was detected on healthy breast cells. Double staining IHC studies revealed co-localization of G-CSFR and TF, G-CSFR and VEGF: VEGFR, as well as TF and VEGF: VEGFR on breast cancer cells and ECs. The results of the study indicate that GCSFR, TF and VEGF: VEGFR expression as well as their co-expression might influence breast cancer biology, and may increase thromboembolic adverse events incidence.

  13. Pinworm Infection

    Science.gov (United States)

    Pinworm infection Overview Pinworm infection is the most common type of intestinal worm infection in the United States and one of the most common worldwide. Pinworms are thin and white, measuring about 1/4 ...

  14. Detection of experimental infections with 99mTc-labeled monoclonal antibodies against TNF-α and interleukin-8

    International Nuclear Information System (INIS)

    Welling, Mick; Feitsma, Hans I.J.; Calame, Wim; Pauwels, Ernest K.J.

    1997-01-01

    This study was designed to assess monoclonal antibodies (MAbs) directed against tumor necrosis factor-α (TNF-α) (anti-TNF) or interleukin-8 (anti-IL-8) as radioactive agents for the detection of Staphylococcus aureus- or Klebsiella pneumoniae-infected thighs in mice. At 5 min (acute infection) or 20 h (established) post-infection, 20 μg of the 99m Tc-labeled MAbs were injected. At various time intervals, the accumulation of the radiotracer in the infected thighs was assessed and expressed as a target-to-nontarget (T/NT) ratio. The binding of 99m Tc-labeled MAbs to circulating mononuclear cells and granulocytes was quantitated 20 h after injection. The pharmacokinetics of the MAbs, in relation to the control agents 99m Tc-labeled polyclonal human immunoglobulin (IgG) and a 99m Tc-labeled nonspecific IgG1 MAb, were also studied. In acute infections, 99m Tc-anti-TNF accumulated to a higher extent (p 99m Tc-IgG and was higher at 0.25 h in K. pneumoniae-infected mice (p 99m Tc-IgG. In established S. aureus and K. pneumoniae infections, 99m Tc-anti-IL-8 detected the infection more intensely than 99m Tc-IgG until 1 h after injection. In both S. aureus and K. pneumoniae infections, localization of sites of infection correlates (p 99m Tc-labeled MAbs to granulocytes and mononuclear cells in both acute and established infections. It was concluded that 99m Tc-labeled MAbs, directed against TNF-α and IL-8, accumulate in bacterial infections in mice to a higher extent than does 99m Tc-IgG after infection and is related to the binding of the antibodies to blood leukocytes. With these 99m Tc-labeled MAbs, information might be gained about the development of an infection

  15. Vector-Borne Infections in Tornado-Displaced and Owner-Relinquished Dogs in Oklahoma, USA.

    Science.gov (United States)

    Barrett, Anne W; Little, Susan E

    2016-06-01

    To determine the prevalence of infection with vector-borne agents in a cross-section of dogs from Oklahoma, where canine vector-borne diseases are common, blood samples were evaluated through serology and molecular analysis. Antibodies reactive to Ehrlichia spp., Rickettsia rickettsii, R. montanensis, and "R. amblyommii" were detected in 10.5% (11/105), 74.3% (78/105), 58.1% (61/105), and 55.2% (58/105) of dogs, respectively. Presence of spotted fever group Rickettsia spp. DNA was identified in 13.1% (8/61) of shelter dogs but not in any pet dogs (0/44). DNA of "R. amblyommii" was confirmed by sequencing, constituting the first report of this agent in a naturally infected dog. Antigen of Dirofilaria immitis was detected in 10.5% (11/105) and 16.2% (17/105) of samples before and after heat treatment, respectively. In total, 87.6% (92/105) of the dogs had evidence of infection with at least one vector-borne disease agent, confirming high risk of exposure to multiple vector-borne disease agents, several of which are zoonotic.

  16. Radionuclide imaging of spinal infections

    International Nuclear Information System (INIS)

    Gemmel, Filip; Dumarey, Nicolas; Palestro, Christopher J.

    2006-01-01

    The diagnosis of spinal infection, with or without implants, has been a challenge for physicians for many years. Spinal infections are now being recognised more frequently, owing to aging of the population and the increasing use of spinal-fusion surgery. The diagnosis in many cases is delayed, and this may result in permanent neurological damage or even death. Laboratory evidence of infection is variable. Conventional radiography and radionuclide bone imaging lack both sensitivity and specificity. Neither in vitro labelled leucocyte scintigraphy nor 99m Tc-anti-granulocyte antibody scintigraphy is especially useful, because of the frequency with which spinal infection presents as a non-specific photopenic area on these tests. Sequential bone/gallium imaging and 67 Ga-SPECT are currently the radionuclide procedures of choice for spinal osteomyelitis, but these tests lack specificity, suffer from poor spatial resolution and require several days to complete. [ 18 F]Fluoro-2-deoxy-D-glucose (FDG) PET is a promising technique for diagnosing spinal infection, and has several potential advantages over conventional radionuclide tests. The study is sensitive and is completed in a single session, and image quality is superior to that obtained with single-photon emitting tracers. The specificity of FDG-PET may also be superior to that of conventional tracers because degenerative bone disease and fractures usually do not produce intense FDG uptake; moreover, spinal implants do not affect FDG imaging. However, FDG-PET images have to be read with caution in patients with instrumented spinal-fusion surgery since non-specific accumulation of FDG around the fusion material is not uncommon. In the future, PET-CT will likely provide more precise localisation of abnormalities. FDG-PET may prove to be useful for monitoring response to treatment in patients with spinal osteomyelitis. Other tracers for diagnosing spinal osteomyelitis are also under investigation, including radiolabelled

  17. Radionuclide imaging of spinal infections

    Energy Technology Data Exchange (ETDEWEB)

    Gemmel, Filip [Ghent Maria-Middelares, General Hospital, Division of Nuclear Medicine, Ghent (Belgium); Medical Center Leeuwarden (MCL), Division of Nuclear Medicine, Henri Dunantweg 2, Postbus 888, Leeuwarden (Netherlands); Dumarey, Nicolas [Universite Libre de Bruxelles, Hopital Erasme, Division of Nuclear Medicine, Brussels (Belgium); Palestro, Christopher J. [Long Island Jewish Medical Center, Division of Nuclear Medicine, Long Island, NY (United States)

    2006-10-15

    The diagnosis of spinal infection, with or without implants, has been a challenge for physicians for many years. Spinal infections are now being recognised more frequently, owing to aging of the population and the increasing use of spinal-fusion surgery. The diagnosis in many cases is delayed, and this may result in permanent neurological damage or even death. Laboratory evidence of infection is variable. Conventional radiography and radionuclide bone imaging lack both sensitivity and specificity. Neither in vitro labelled leucocyte scintigraphy nor {sup 99m}Tc-anti-granulocyte antibody scintigraphy is especially useful, because of the frequency with which spinal infection presents as a non-specific photopenic area on these tests. Sequential bone/gallium imaging and {sup 67}Ga-SPECT are currently the radionuclide procedures of choice for spinal osteomyelitis, but these tests lack specificity, suffer from poor spatial resolution and require several days to complete. [{sup 18}F]Fluoro-2-deoxy-D-glucose (FDG) PET is a promising technique for diagnosing spinal infection, and has several potential advantages over conventional radionuclide tests. The study is sensitive and is completed in a single session, and image quality is superior to that obtained with single-photon emitting tracers. The specificity of FDG-PET may also be superior to that of conventional tracers because degenerative bone disease and fractures usually do not produce intense FDG uptake; moreover, spinal implants do not affect FDG imaging. However, FDG-PET images have to be read with caution in patients with instrumented spinal-fusion surgery since non-specific accumulation of FDG around the fusion material is not uncommon. In the future, PET-CT will likely provide more precise localisation of abnormalities. FDG-PET may prove to be useful for monitoring response to treatment in patients with spinal osteomyelitis. Other tracers for diagnosing spinal osteomyelitis are also under investigation, including

  18. Molecular cloning, sequencing and structural studies of granulocyte-macrophage colony-stimulating factor (GM-CSF) from Indian water buffalo (Bubalus bubalis)

    KAUST Repository

    Sugumar, Thennarasu; Ganesan, Pugalenthi; Harishankar, Murugesan; Dhinakar Raj, Gopal

    2013-01-01

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is essential for growth and development of progenitors of granulocytes and monocytes/macrophages. In this study, we report molecular cloning, sequencing and characterization of GM-CSF from Indian water buffalo, Bubalus bubalis. In addition, we performed sequence and structural analysis for buffalo GM-CSF. Buffalo GM-CSF has been compared with 17 mammalian GM-CSFs using multiple sequence alignment and phylogenetic tree. Three-dimensional model for buffalo GM-CSF and human receptor complex was built using homology modelling to study cross-reactivity between two species. Detailed analysis was performed to study GM-CSF interface and various interactions at the interface. © 2013 John Wiley & Sons Ltd.

  19. Molecular cloning, sequencing and structural studies of granulocyte-macrophage colony-stimulating factor (GM-CSF) from Indian water buffalo (Bubalus bubalis)

    KAUST Repository

    Sugumar, Thennarasu

    2013-06-25

    Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a cytokine that is essential for growth and development of progenitors of granulocytes and monocytes/macrophages. In this study, we report molecular cloning, sequencing and characterization of GM-CSF from Indian water buffalo, Bubalus bubalis. In addition, we performed sequence and structural analysis for buffalo GM-CSF. Buffalo GM-CSF has been compared with 17 mammalian GM-CSFs using multiple sequence alignment and phylogenetic tree. Three-dimensional model for buffalo GM-CSF and human receptor complex was built using homology modelling to study cross-reactivity between two species. Detailed analysis was performed to study GM-CSF interface and various interactions at the interface. © 2013 John Wiley & Sons Ltd.

  20. A methylcellulose microculture assay for the in vitro assessment of drug toxicity on granulocyte/macrophage progenitors (CFU-GM).

    Science.gov (United States)

    Pessina, Augusto; Croera, Cristina; Bayo, Maria; Malerba, Ilaria; Passardi, Laura; Cavicchini, Loredana; Neri, Maria G; Gribaldo, Laura

    2004-03-01

    In a recent prevalidation study, the use of a methylcellulose colony-forming unit-granulocyte/macrophage (CFU-GM) macroassay for two independent in vitro tests (human and murine cell based) was suggested for quantifying the potential haematotoxicity of xenobiotics. In this paper, we describe the transfer of the macroassay to a 96-well plate microassay, in which the linearity of the response was studied (both in terms of CFU-GM and optical density [OD] versus the number of cells cultured), and the inhibitory concentration (IC) values for doxorubicin, 5-fluorouracil and taxol were determined and compared with those obtained by using the original macroassay. Fresh murine bone marrow and human umbilical cord blood mononuclear cells were used as a source of myeloid progenitors. The cells were cultured in methylcellulose containing granulocyte/macrophage-colony-stimulating factor, and in the presence of increasing drug concentrations. The cloning capacity of the progenitors was measured both as the number of colonies counted manually (CFU-GM), and as OD evaluated with an automated plate reader in an MTT test. Our results show that, in the microassay, up to 20 colonies/well could be easily counted, and that this range (20 to zero) gave a regression line from which IC values were calculated, which were very close to those obtained by using the macroassay (where the range of colony numbers was from 100 to zero). The test did not give good results when the OD (instead of the colony count) was used as the endpoint, because, although a high coefficient of determination was obtained, the OD values ranged from 0.6 to zero and the IC values determined were not comparable to those obtained by manual counts. The use of the microassay dramatically reduces the quantity of methylcellulose needed, and permits hundreds of cultures to be processed in the same experiment, contributing to significant reductions in both the work involved and the cost. A further important benefit is a

  1. Thermo-radiosensitivity of the granulocyte and macrophage precursor cells of mice. I.-Development of the in vivo culture and effects induced by the hyperthermia

    International Nuclear Information System (INIS)

    Bueren, J. A.; Nieto, M.

    1983-01-01

    The present report shows the agar diffusion chamber technique for culturing granulocyte- macrophage precursor cells, obtained from mice bone marrow. Diffusion chambers containing the bone marrow suspension are implanted intraperitoneally Into mice and constitute a compartment which avoids the migration of cells, but allows the transit of the mouse biological fluxes, necessary for the cellular proliferation. By means of this technique, we studied the lethal effects of the hyperthermia on the precursors and their capacity to repair sublethal damage. (Author) 129 refs

  2. Recombinant Granulocyte-Macrophage Colony-Stimulating Factor (rGM-CSF) : A Review of its Pharmacological Properties and Prospective Role in the Management of Myelosuppression.

    Science.gov (United States)

    Grant, Susan M; Heel, Rennie C

    1992-04-01

    Recombinant granulocyte-macrophage colony-stimulating factor (rGM-CSF) is a polypeptide hormone produced through recombinant DNA technologies in glycosylated (yeast or mammalian expression systems) or nonglycosylated (Escherichia coli expression system) form. It is a multilineage haematopoietin which stimulates proliferation and differentiation of bone marrow myeloid progenitors and increases peripheral white blood cell counts when administered systemically. Treatment is generally well tolerated, although mild to moderate flu-like symptoms are common and rGM-CSF-induced fever and fluid retention may be problematic in occasional patients. rGM-CSF accelerates recovery of peripheral neutrophil counts after bone marrow transplantation, and results of a placebo-controlled randomised trial correlate this with reduced infectious episodes and shortened length of hospitalisation in patients with lymphoid malignancies. A substantial number of patients with graft failure after bone marrow transplantation also respond to rGM-CSF. The duration of myelosuppression secondary to cancer chemotherapy can be significantly reduced by rGM-CSF which has permitted investigation of antineoplastic dose-intensity escalation. In some haematopoietic disorders (e.g. aplastic anaemia, myelodysplasia and neutropenia secondary to HIV infection and antiviral therapy), rGM-CSF produces clinically useful increases in peripheral blood granulocyte counts, although the effect is generally not sustained after drug withdrawal. The potential for rGM-CSF to stimulate proliferation of the abnormal clone in myelodysplasia and in acute myelogenous leukaemia following induction therapy is of concern. Available data suggest, however, that with appropriate monitoring and exclusion of high-risk patients this serious potential risk can be avoided, and that myelopoiesis is enhanced in such patients by rGM-CSF treatment. Recombinant colony-stimulating factors are a new therapeutic modality; hence many aspects of

  3. In vivo changes of hemopoietic progenitors and the expression of the interleukin 5 gene in eosinophilic mice infected with Toxocara canis.

    Science.gov (United States)

    Yamaguchi, Y; Matsui, T; Kasahara, T; Etoh, S; Tominaga, A; Takatsu, K; Miura, Y; Suda, T

    1990-12-01

    It has been demonstrated that purified recombinant interleukin 5 (rIL-5) supports the terminal differentiation and proliferation of eosinophilic precursors in vitro and plays an important role in increasing the functional activities of eosinophils. In this study, we examined the hemopoietic changes and analyzed murine (m) IL-5 mRNA expression in eosinophilic mice infected with the helminth Toxocara canis. In eosinophilic mice, eosinophils increased in number in both bone marrow and spleen. However, the number of eosinophilic precursors increased markedly in spleen cells of eosinophilic mice but remained relatively constant in the bone marrow. In the presence of granulocyte colony-stimulating factor (G-CSF), the number of granulocytic precursors increased in the spleen cells of eosinophilic mice. From these findings, the condition of eosinophilopoiesis in eosinophilic mice is accompanied by an increase in granulocyte-macrophage progenitors as well as eosinophil progenitors. Using Northern blot analysis, a weak but definite band corresponding to mIL-5 mRNA was detected in spleen cells of mice 4 and 5 days after helminthic infection. In addition, these data were confirmed by in vitro polymerase chain reaction (PCR) amplification of mRNA obtained from these spleen cells. Finally, injections of a monoclonal antibody against mIL-5 completely suppressed the blood eosinophilia in mice infected with T. canis. In conclusion, IL-5 is suggested to play a major role in eosinophilopoiesis in vivo.

  4. Radiolabeled white blood cells and direct targeting of micro-organisms for infection imaging

    International Nuclear Information System (INIS)

    Kumar, V.

    2005-01-01

    Infection imaging is complicated due to multitude of factors interfering with the design of radiopharmaceuticals. More than 3 decades ago, labeled leukocytes have been introduced for infection imaging and new radiopharmaceuticals have been emerging on regular basis. However, labeled leukocytes by in vivo and in vitro methods are very effective for diagnosing various lesions such as osteomyelitis, cellulitis, diabetic foot, Crohn's disease, inflammatory bowel disease and in distinguishing prosthetic infection from loosening of prosthesis. But in vitro labeling method using 1 11I n-oxine, 9 9mT c-HMPAO or 9 9mT c-stannous colloid have the inherent limitation of personnel safety risks of infection and cross contamination. To overcome these problems, attempts have been made to directly target leukocytes by in vivo labeling techniques. There are several receptors present on the leukocytes and the granulocytes, which can be targeted with suitable ligands. These will include anti-NCA90-Fab, murine MoAb IgG 1 that is cross-reactive to antigen 95 on neutrophils, anti-CD15 antigen and DPC-11870 that targets the leukotriene B4 receptors of granulocytes. In a new approach, 9 9mT c-labeled ciprofloxacin has been developed to directly target live bacteria to detect infection by in vivo method. This approach showed considerable promise in the preliminary studies but clinical trials showed limitations. Analogs of a natural mammalian antimicrobial agents, such as Ubiquicidin were successful in animal studies and have now entered clinical trials. 9 9mT c-labeled fluconazole (a fungal antibiotic) and labeled Chitinase (1 23I -ChiB E144Q), have been developed to detect fungal infection. The ability to distinguish between fungal and bacterial infection is considered important, as patients undergoing chemotherapy are prone to fungal infection. Undoubtedly, the new trends and new radiopharmaceuticals developed for infection and inflammation imaging have contributed towards a better

  5. Selective engraftment of the granulocyte compartment after allogeneic bone marrow transplantation in a patient with severe aplastic anemia.

    Science.gov (United States)

    Barriga, F J; Legues, M E; Bertin, P

    1996-05-01

    We present a patient with severe aplastic anemia who had partial engraftment with full chimerism after allogeneic bone marrow transplantation from an HLA identical sibling. A 3-year-old girl with severe aplastic anemia (SAA) received a bone marrow transplantation (BMT) from an HLA identical brother 9 months after her diagnosis. Before BMT she was red blood cell tranfusion dependent, had an absolute neutrophil count (ANC) of 1,000-1,500 x 10(9)/1 and a platelet count of 15-19,000 x 10(9)/1. She was conditioned with 800 cGy total body irradiation (TBI) and cyclophosphamide and received 3X10(8) nucleated cells/kg. She reached an ANC of 1500 x 10(9)/1 on day +35 but her reticulocyte and platelet counts did not recover. A bone marrow aspirate and biopsy post BMT showed hypoplasia with marked decrease in megakaryocyte and red blood cell precursors. The granulocyte compartment showed a left shift with predominance of promyelocytes and myelocytes. The karyotype showed full chimerism (46,XY) with no 46,XX metaphases. This case illustrates the possibility of a bone marrow microenvironment defect as the cause of SAA.

  6. Effect of granulocyte colony stimulating factor (G-CSF on IVF outcomes in infertile women: An RCT

    Directory of Open Access Journals (Sweden)

    Maryam Eftekhar

    2016-05-01

    Full Text Available Background: Despite major advances in assisted reproductive techniques, the implantation rates remain relatively low. Some studies have demonstrated that intrauterine infusion of granulocyte colony stimulating factor (G-CSF improves implantation in infertile women. Objective: To assess the G-CSF effects on IVF outcomes in women with normal endometrial thickness. Materials and methods: In this randomized controlled clinical trial, 100 infertile women with normal endometrial thickness who were candidate for IVF were evaluated in two groups. Exclusion criteria were positive history of repeated implantation failure (RIF, endocrine disorders, severe endometriosis, congenital or acquired uterine anomaly and contraindication for G-CSF (renal disease, sickle cell disease, or malignancy. In G-CSF group (n=50, 300 μg trans cervical intrauterine of G-CSF was administered at the oocyte retrieval day. Controls (n=50 were treated with standard protocol. Chemical, clinical and ongoing pregnancy rates, implantation rate, and miscarriage rate were compared between groups. Results: Number of total and mature oocytes (MII, two pronuclei (2PN, total embryos, transferred embryos, quality of transferred embryos, and fertilization rate did not differ significantly between two groups. So there were no significant differences between groups in chemical, clinical and ongoing pregnancy rate, implantation rate, and miscarriage rate Conclusion: our result showed in normal IVF patients with normal endometrial thickness, the intrauterine infusion of G-CSF did not improve pregnancy outcomes.

  7. Granulocyte Macrophage Colony Stimulating Factor Supplementation in Culture Media for Subfertile Women Undergoing Assisted Reproduction Technologies: A Systematic Review

    Science.gov (United States)

    Siristatidis, Charalampos; Vogiatzi, Paraskevi; Salamalekis, George; Creatsa, Maria; Vrachnis, Nikos; Glujovsky, Demián; Iliodromiti, Zoe; Chrelias, Charalampos

    2013-01-01

    Granulocyte macrophage colony stimulating factor (GM-CSF) is a cytokine/growth factor produced by epithelial cells that exerts embryotrophic effects during the early stages of embryo development. We performed a systematic review, and six studies that were performed in humans undergoing assisted reproduction technologies (ART) were located. We wanted to evaluate if embryo culture media supplementation with GM-CSF could improve success rates. As the type of studies and the outcome parameters investigated were heterogeneous, we decided not to perform a meta-analysis. Most of them had a trend favoring the supplementation with GM-CSF, when outcomes were measured in terms of increased percentage of good-quality embryos reaching the blastocyst stage, improved hatching initiation and number of cells in the blastocyst, and reduction of cell death. However, no statistically significant differences were found in implantation and pregnancy rates in all apart from one large multicenter trial, which reported favorable outcomes, in terms of implantation and live birth rates. We propose properly conducted and adequately powered randomized controlled trials (RCTs) to further validate and extrapolate the current findings with the live birth rate to be the primary outcome measure. PMID:23509457

  8. Combined application of alginate dressing and human granulocyte-macrophage colony stimulating factor promotes healing in refractory chronic skin ulcers.

    Science.gov (United States)

    Huang, Guobao; Sun, Tangqing; Zhang, Lei; Wu, Qiuhe; Zhang, Keyan; Tian, Qingfen; Huo, Ran

    2014-06-01

    The aim of the present study was to evaluate the clinical therapeutic effect of the combined application of alginate and recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) on the healing of refractory chronic skin ulcers. A single center, three arm, randomized study was performed at Jinan Central Hospital (Jinan, Shandong, China). A total of 60 patients with refractory chronic skin ulcers, which persisted for >1 month, were enrolled and randomly assigned into one of the following three groups: alginate dressing/rhGM-CSF group (group A), rhGM-CSF only group (group B) and conventional (vaseline dressing) group (group C). The wound area rate was measured, granulation and color were observed and pain was evaluated. The data were summarized and statistical analysis was performed. The results demonstrated that group A exhibited a significantly faster wound healing rate and lower pain score compared with the other groups (PCSF for the treatment of refractory chronic skin ulcers demonstrated significant advantages. It promoted the growth of granulation tissue, accelerated re-epithelialization and also effectively reduced wound pain, and thus improved the quality of life for the patient. This suggests that the combined application of alginate and rhGM-CSF may be an effective therapeutic strategy for the clinical treatment of refractory chronic skin ulcers.

  9. Engineering a pharmacologically superior form of granulocyte-colony-stimulating factor by fusion with gelatin-like-protein polymer.

    Science.gov (United States)

    Huang, Yan-Shan; Wen, Xiao-Fang; Wu, Yi-Liang; Wang, Ye-Fei; Fan, Min; Yang, Zhi-Yu; Liu, Wei; Zhou, Lin-Fu

    2010-03-01

    The plasma half-life of therapeutic proteins is a critical factor in many clinical applications. Therefore, new strategies to prolong plasma half-life of long-acting peptides and protein drugs are in high demand. Here, we designed an artificial gelatin-like protein (GLK) and fused this hydrophilic GLK polymer to granulocyte-colony-stimulating factor (G-CSF) to generate a chimeric GLK/G-CSF fusion protein. The genetically engineered recombinant GLK/G-CSF (rGLK/G-CSF) fusion protein was purified from Pichia pastoris. In vitro studies demonstrated that rGLK/G-CSF possessed an enlarged hydrodynamic radius, improved thermal stability and retained full bioactivity compared to unfused G-CSF. Following a single subcutaneous administration to rats, the rGLK/G-CSF fusion protein displayed a slower plasma clearance rate and stimulated greater and longer lasting increases in circulating white blood cells than G-CSF. Our findings indicate that fusion with this artificial, hydrophilic, GLK polymer provides many advantages in the construction of a potent hematopoietic factor with extended plasma half-life. This approach could be easily applied to other therapeutic proteins and have important clinical applications. (c) 2009 Elsevier B.V. All rights reserved.

  10. The safety and clinical efficacy of recombinant human granulocyte colony stimulating factor injection for colon cancer patients undergoing chemotherapy

    Directory of Open Access Journals (Sweden)

    Jie Chen

    Full Text Available Summary Objective: The present study was designed to evaluate safety and efficacy of recombinant human granulocyte colony stimulating factor (G-CSF injection and whether this regimen could reduce the incidence of adverse events caused by chemotherapy. Method: A total of 100 patients with colon cancer who were treated with chemotherapy in our hospital from January 2011 to December 2014 were randomly divided into two groups, with 50 patients in each group. The patients in the treatment group received G-CSF 24 hours after chemotherapy for consecutive three days; the patients in the control group received the same dose of normal saline. Routine blood tests were performed 7 days and 14 days after chemotherapy. Results: Compared with the control group, the incidences of febrile neutropenia and leukocytopenia in the treatment group were significantly lower (p<0.05. In addition, the incidence of liver dysfunction in the treatment group was lower than that of the control group, without statistical significance. The incidence of myalgia in the treatment was higher than that of the control group without statistical significance. Conclusion: The present study indicated that G-CSF injection after chemotherapy is safe and effective for preventing adverse events in colon cancer patients with chemotherapy.

  11. The optimal use of granulocyte macrophage colony stimulating factor in radiation induced mucositis in head and neck squamous cell carcinoma.

    Directory of Open Access Journals (Sweden)

    Patni Nidhi

    2005-01-01

    Full Text Available Objective: Evaluation of response of granulocyte macrophage colony stimulating factor (GM-CSF on acute radiation toxicity profile in head and neck squamous cell carcinoma. Methods and Materials: Thirty three patients with proven stage I or II head & neck carcinoma received conventional external beam radiation therapy. Out of these, six patients received postoperative adjuvant therapy while remaining 27 received definitive RT. Patients were given 100 mcg GM-CSF subcutaneously per day along with radiation after they developed grade 2 mucositis and /or grade 2 dysphagia and / or complained of moderate pain. GM-CSF was administered till there was a subjective relief or objective response. Patients were evaluated for oral ulceration, swallowing status, pain and weight loss. Response to the treatment and patient outcome was assessed. Results: There was a decreased severity of mucositis and dysphagia in the evaluated patients. None of the patients suffered severe pain or required opioids. The mean weight loss was only 1.94%. Minimal side effects were experienced with GM-CSF. Conclusions: GM-CSF reduces the severity of acute side effects of radiation therapy thereby allowing completion of the treatment without interruption. Its remarkable response needs to be evaluated further in large randomized trials. The time of initiation and cessation of GM-CSF during radiation therapy and the required dose needs to be established.

  12. Role of FDG PET/CT in Diagnostic Evaluation of Granulocytic Sarcomas: A Series of 12 Patients.

    Science.gov (United States)

    Chandra, Piyush; Dhake, Sanket; Purandare, Nilendu; Agrawal, Archi; Shah, Sneha; Rangarajan, Venkatesh

    2017-01-01

    Granulocytic sarcoma (GS) is a rare extramedullary manifestation in patients with acute myeloid leukemia (AML), which can precede the diagnosis or occur in the posttreatment setting. Unlike its established role in other hematological malignancies like Hodgkin's on non-Hodgkin's disease, the exact role of positron emission tomography/computed tomography (PET/CT) in AML with or without GS remains to be defined. We retrospectively reviewed PET/CT scans of 12 patients with histologically proven GS. Marrow examination of these patients identified nine patients with isolated GS (without existent leukemia) and three patients with coexistent leukemia. PET/CT accurately identified all clinically evident GS in all 12 patients at initial staging and at follow-up with tumors, showing moderate to high 2-deoxy-2-fluoro-D-glucose uptake. Coexistent marrow disease was seen on PET/CT in three patients, which was confirmed on histopathology. In the same patients, PET/CT also detected additional sites of extramedullary disease in 66.6% (n = 8), which was either clinically occult or not evident on routine CT. PET/CT appears to be a highly sensitive imaging modality in diagnostic evaluation of GS. The most important indication of using PET/CT in these cases is to identify additional sites of clinically occult extramedullary disease, which can potentially impact treatment decisions and outcomes.

  13. IL-8 Expression in Granulocytic Epithelial Lesions of Idiopathic Duct-centric Pancreatitis (Type 2 Autoimmune Pancreatitis).

    Science.gov (United States)

    Ku, Yuna; Hong, Seung-Mo; Fujikura, Kohei; Kim, Sung Joo; Akita, Masayuki; Abe-Suzuki, Shiho; Shiomi, Hideyuki; Masuda, Atsuhiro; Itoh, Tomoo; Azuma, Takeshi; Kim, Myung-Hwan; Zen, Yoh

    2017-08-01

    Type 2 autoimmune pancreatitis (type 2 AIP) develops in isolation or sometimes in association with ulcerative colitis. Its diagnosis requires the histologic confirmation of granulocytic epithelial lesions (GELs) with no diagnostic biomarker currently available. This study aimed to elucidate the tissue expression of cytokines and their diagnostic value in this condition. In quantitative polymerase chain reaction for multiple cytokines using tissue-derived mRNA, the expression level of interleukin (IL)-8 was markedly higher in type 2 AIP than in type 1 AIP (Ppancreatitis adjacent to pancreatic cancers (peritumoral pancreatitis) exhibited IL-8 expression in the epithelium (3/12; 25%) and inflammatory cells (10/12; 83%), expression levels were significantly lower than those in type 2 AIP (Ppancreatitis with 92% sensitivity and 92% to 100% specificity. Furthermore, CD3/IL-8-coexpressing lymphocytes were almost restricted to type 2 AIP. Interestingly, a similar pattern of IL-8 expression was also observed in colonic biopsies of ulcerative colitis. In conclusion, the overexpression of IL-8 may underlie the development of GELs in type 2 AIP, and IL-8 immunostaining or IL-8/CD3 double staining may become an ancillary method for its diagnosis. The similar expression pattern of IL-8 in ulcerative colitis also suggests a pathogenetic link between the 2 conditions.

  14. Simplified in vitro refolding and purification of recombinant human granulocyte colony stimulating factor using protein folding cation exchange chromatography.

    Science.gov (United States)

    Vemula, Sandeep; Dedaniya, Akshay; Thunuguntla, Rahul; Mallu, Maheswara Reddy; Parupudi, Pavani; Ronda, Srinivasa Reddy

    2015-01-30

    Protein folding-strong cation exchange chromatography (PF-SCX) has been employed for efficient refolding with simultaneous purification of recombinant human granulocyte colony stimulating factor (rhG-CSF). To acquire a soluble form of renatured and purified rhG-CSF, various chromatographic conditions, including the mobile phase composition and pH was evaluated. Additionally, the effects of additives such as urea, amino acids, polyols, sugars, oxidizing agents and their amalgamations were also investigated. Under the optimal conditions, rhG-CSF was efficaciously solubilized, refolded and simultaneously purified by SCX in a single step. The experimental results using ribose (2.0M) and arginine (0.6M) combination were found to be satisfactory with mass yield, purity and specific activity of 71%, ≥99% and 2.6×10(8)IU/mg respectively. Through this investigation, we concluded that the SCX refolding method was more efficient than conventional methods which has immense potential for the large-scale production of purified rhG-CSF. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Increased biological activity of deglycosylated recombinant human granulocyte/macrophage colony-stimulating factor produced by yeast or animal cells

    International Nuclear Information System (INIS)

    Moonen, P.; Mermod, J.J.; Ernst, J.F.; Hirschi, M.; DeLamarter, J.F.

    1987-01-01

    Human granulocyte/macrophage colony-stimulating factor (hGM-CSF) produced by several recombinant sources including Escherichia coli, yeast, and animal cells was studied. Recombinant animal cells produced hGM-CSF in low quantities and in multiple forms of varying size. Mammalian hGM-CSF was purified 200,000-fold using immunoaffinity and lectin chromatography. Partially purified proteins produced in yeast and mammalian cells were assayed for the effects of deglycosylation. Following enzymatic deglycosylation, immunoreactivity was measured by radioimmunoassay and biological activity was measured in vitro on responsive human primary cells. Removal of N-linked oligosaccharides from both proteins increased their immunoreactivities by 4- to 8-fold. Removal of these oligosaccharides also increased their specific biological activities about 20-fold, to reach approximately the specific activity of recombinant hGM-CSF from E. coli. The E. coli produced-protein-lacking any carbohydrate- had by far the highest specific activity observed for the recombinant hGM-CSFs

  16. Granulocyte colony stimulating factor priming chemotherapy is more effective than standard chemotherapy as salvage therapy in relapsed acute myeloid leukemia.

    Science.gov (United States)

    Shen, Ying; He, Aili; Wang, Fangxia; Bai, Ju; Wang, Jianli; Zhao, Wanhong; Zhang, Wanggang; Cao, Xingmei; Chen, Yinxia; Liu, Jie; Ma, Xiaorong; Chen, Hongli; Feng, Yuandong; Yang, Yun

    2017-12-29

    To improve the complete remission (CR) rate of newly diagnosed acute myeloid leukemia (AML) patients and alleviate the severe side effects of double induction chemotherapy, we combined a standard regimen with granulocyte colony-stimulating factor (G-CSF) priming chemotherapy to compose a new double induction regimen for AML patients who failed to achieve CR after the first course. Ninety-seven patients with AML who did not achieve CR after the first course of standard chemotherapy were enrolled. Among them, 45 patients received G-CSF priming combined with low-dose chemotherapy during days 20-22 of the first course of chemotherapy, serving as priming group, 52 patients were administered standard chemotherapy again, serving as control group. Between the two groups there were no differences in the French-American-British (FAB) classification, risk status, the first course of chemotherapy, blood cell count or blasts percentage of bone marrow before the second course. But the CR rate was significantly higher and the adverse effect was much lower in the priming group than the control group. Cox multivariate regression analysis showed that WBC level before the second course and the selection of the second chemotherapy regimen were two independent factors for long survival of patients. These results elucidate that standard chemotherapy followed by G-CSF priming new double induction chemotherapy is an effective method for AML patients to improve CR rate and reduce adverse effects. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  17. Both IL-1β and TNF-α Regulate NGAL Expression in Polymorphonuclear Granulocytes of Chronic Hemodialysis Patients

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    Adriana Arena

    2010-01-01

    Full Text Available Background. NGAL is involved in modulation of the inflammatory response and is found in the sera of uremic patients. We investigated whether hemodiafiltration (HDF could influence the ability of polymorphonuclear granulocytes (PMGs to release NGAL. The involvement of interleukin- (IL-1β and tumor necrosis factor- (TNF-α on NGAL release was evaluated. Methods. We studied end-stage renal disease (ESRD patients at the start of dialysis (Pre-HDF and at the end of treatment (Post-HDF and 18 healthy subjects (HSs. Peripheral venous blood was taken from HDF patients at the start of dialysis and at the end of treatment. Results. PMGs obtained from ESRD patients were hyporesponsive to LPS treatment, with respect to PMG from HS. IL-1β and TNF-α produced by PMG from post-HDF patients were higher than those obtained by PMG from pre-HDF. Neutralization of IL-1β, but not of TNF-α, determined a clear-cut production of NGAL in PMG from healthy donors. On the contrary, specific induction of NGAL in PMG from uremic patients was dependent on the presence in supernatants of IL-1β and TNF-α. Conclusion. Our data demonstrate that in PMG from healthy subjects, NGAL production was supported solely by IL-1β, whereas in PMG from HDF patients, NGAL production was supported by IL-1β, TNF-α.

  18. Biological properties in vitro of a combination of recombinant murine interleukin-3 and granulocyte-macrophage colony-stimulating factor.

    Science.gov (United States)

    Riklis, I; Kletter, Y; Bleiberg, I; Fabian, I

    1989-04-01

    The effect of recombinant murine interleukin-3 (rIL-3) and recombinant murine granulocyte-macrophage colony-stimulating factor (rGM-CSF) on in vitro murine myeloid progenitor cell (CFU-C) growth and on the function of murine resident peritoneal macrophages was investigated. Both rIL-3 and rGM-CSF are known to support the growth of CFU-C and, when combined, were found to act synergistically to induce the development of an increased number of CFU-C. The distribution pattern of myeloid colonies in the presence of these two growth factors was in general similar to that in the presence of rGM-CSF alone. Both rGM-CSF and rIL-3 enhanced the phagocytosis of Candida albicans (CA) by mature macrophages producing an increase in the percentage of phagocytosing cells as well as an increase in the number of yeast particles ingested per cell. No additive effect on the phagocytosis was observed when the two growth factors were added concurrently. rGM-CSF, but not rIL-3, enhanced the killing of CA by macrophages. This killing was inhibited by scavengers of oxygen radicals.

  19. Mobilization of stem cell with granulocyte-colony stimulating factor promotes recovery after traumatic brain injury in rat

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    Mohsen Marzban

    2010-01-01

    Full Text Available Introduction: This study was designed to investigate the effects of granulocyte colony-stimulating factor (G-CSF administration in rats for 6 weeks after traumatic brain injury (TBI. Methods: Adult male Wistar rats (n = 30 were injured with controlled cortical impact device and divided into four groups. The treatment groups (n = 10 each were injected subcutaneously with recombinant human G-CSF. Vehicle group (n=10 received phosphate buffered saline (PBS and only Brdu intraperitoneally. Bromodeoxyuridine (BrdU was used for mitotic labeling. Experimental rats were injected intraperitoneally with BrdU. Rats were killed at 6th week after traumatic brain injury. Neurological functional evaluation of animals was performed before and after injury using neurological severity scores (NSS. Animals were sacrificed 42 days after TBI and brain sections were stained using Brdu immunohistochemistry. Results: Statistically significant improvement in functional outcome was observed in treatment groups when compared with control (p<0.01. This benefit was visible 7 days after TBI and persisted until 42 days (end of trial. Histological analysis showed that Brdu cell positive was more in the lesion boundary zone at treatment animal group than all injected animals. Discussion: We believe that G-CSF therapeutic protocol reported here represents an attractive strategy for the development of a clinically significant noninvasive traumatic brain injury therapy.

  20. Affinity purification of human granulocyte macrophage colony-stimulating factor receptor alpha-chain. Demonstration of binding by photoaffinity labeling

    International Nuclear Information System (INIS)

    Chiba, S.; Shibuya, K.; Miyazono, K.; Tojo, A.; Oka, Y.; Miyagawa, K.; Takaku, F.

    1990-01-01

    The human granulocyte macrophage colony-stimulating factor (GM-CSF) receptor alpha-chain, a low affinity component of the receptor, was solubilized and affinity-purified from human placenta using biotinylated GM-CSF. Scatchard analysis of 125 I-GM-CSF binding to the placental membrane extract disclosed that the GM-CSF receptor had a dissociation constant (Kd) of 0.5-0.8 nM, corresponding to the Kd value of the GM-CSF receptor alpha-chain on the intact placental membrane. Affinity labeling of the solubilized protein using a photoreactive cross-linking agent, N-hydroxysuccinimidyl-4-azidobenzoate (HSAB), demonstrated a single specific band of 70-95 kDa representing a ligand-receptor complex. Approximately 2 g of the placental membrane extract was subjected to a biotinylated GM-CSF-fixed streptavidin-agarose column, resulting in a single major band at 70 kDa on a silver-stained sodium dodecyl sulfate gel. The radioiodination for the purified material disclosed that the purified protein had an approximate molecular mass of 70 kDa and a pI of 6.6. Binding activity of the purified material was demonstrated by photoaffinity labeling using HSAB- 125 I-GM-CSF, producing a similar specific band at 70-95 kDa as was demonstrated for the crude protein

  1. Nuclear proteins interacting with the promoter region of the human granulocyte/macrophage colony-stimulating factor gene

    International Nuclear Information System (INIS)

    Shannon, M.F.; Gamble, J.R.; Vadas, M.A.

    1988-01-01

    The gene for human granulocyte/macrophage colony-stimulating factor (GM-CSF) is expressed in a tissue-specific as well as an activation-dependent manner. The interaction of nuclear proteins with the promoter region of the GM-CSF gene that is likely to be responsible for this pattern of GM-CSF expression was investigated. The authors show that nuclear proteins interact with DNA fragments from the GM-CSF promoter in a cell-specific manner. A region spanning two cytokine-specific sequences, cytokine 1 (CK-1, 5', GAGATTCCAC 3') and cytokine 2 (CK-2, 5' TCAGGTA 3') bound two nuclear proteins from GM-CSF-expressing cells in gel retardation assays. NF-GMb was inducible with phorbol 12-myristate 13-acetate and accompanied induction of GM-CSF message. NF-GMb was absent in cell lines not producing GM-CSF, some of which had other distinct binding proteins. NF-GMa and NF-GMb eluted from a heparin-Sepharose column at 0.3 and 0.6 M KCl, respectively. They hypothesize that the sequences CK-1 and CK-2 bind specific proteins and regulate GM-CSF transcription

  2. The role of granulocyte macrophage colony stimulating factor (GM-CSF) in radiation-induced tumor cell migration.

    Science.gov (United States)

    Vilalta, Marta; Brune, Jourdan; Rafat, Marjan; Soto, Luis; Graves, Edward E

    2018-03-13

    Recently it has been observed in preclinical models that that radiation enhances the recruitment of circulating tumor cells to primary tumors, and results in tumor regrowth after treatment. This process may have implications for clinical radiotherapy, which improves control of a number of tumor types but which, despite continued dose escalation and aggressive fractionation, is unable to fully prevent local recurrences. By irradiating a single tumor within an animal bearing multiple lesions, we observed an increase in tumor cell migration to irradiated and unirradiated sites, suggesting a systemic component to this process. Previous work has identified the cytokine GM-CSF, produced by tumor cells following irradiation, as a key effector of this process. We evaluated the ability of systemic injections of a PEGylated form of GM-CSF to stimulate tumor cell migration. While increases in invasion and migration were observed for tumor cells in a transwell assay, we found that daily injections of PEG-GM-CSF to tumor-bearing animals did not increase migration of cells to tumors, despite the anticipated changes in circulating levels of granulocytes and monocytes produced by this treatment. Combination of PEG-GM-CSF treatment with radiation also did not increase tumor cell migration. These findings suggest that clinical use of GM-CSF to treat neutropenia in cancer patients will not have negative effects on the aggressiveness of residual cancer cells. However, further work is needed to characterize the mechanism by which GM-CSF facilitates systemic recruitment of trafficking tumor cells to tumors.

  3. Peripheral Blood CD64 Levels Decrease in Crohn’s Disease following Granulocyte and Monocyte Adsorptive Apheresis

    Directory of Open Access Journals (Sweden)

    Toshimi Chiba

    2011-12-01

    Full Text Available Granulocyte and monocyte adsorptive apheresis (GMA is reportedly useful as induction therapy for Crohn’s disease (CD. However, the effects of GMA on CD64 have not been well characterized. We report here our assessment of CD64 expression on neutrophils before and after treatment with GMA in two patients with CD. The severity of CD was assessed with the CD activity index (CDAI. The duration of each GMA session was 60 min at a flow rate of 30 ml/min as per protocol. CD64 expression on neutrophils was measured by analyzing whole blood with a FACScan flow cytometer. In case 1, CD64 levels after each session of GMA tended to decrease compared to pretreatment levels, whereas in case 2, CD64 levels dropped significantly after treatment. The CDAI decreased after GMA in both cases 1 and 2. A significant correlation was noted between CDAI scores and CD64 levels in both cases. In conclusion, GMA reduced blood CD64 levels, which would be an important factor for the decrease of CDAI scores.

  4. Granulocyte colony-stimulating factor in toxic epidermal necrolysis (TEN) and Chelsea & Westminster TEN management protocol [corrected].

    Science.gov (United States)

    de Sica-Chapman, A; Williams, G; Soni, N; Bunker, C B

    2010-04-01

    Toxic epidermal necrolysis (TEN) is a rare but life-threatening, allergic drug reaction. Skin blistering with epidermal and mucosal necrolysis with subsequent detachment from an inflamed underlying dermis is a hallmark of the condition. The pathogenesis of TEN is not well understood, accounting for controversies about its management and significant delay in initiating potentially beneficial therapy. There are no management protocols based on a robust evidence base. Prompt recognition of the diagnosis and consensus on early management initiatives are necessary in order to improve outcomes and survival in TEN. To date, TEN management has been directed at arresting the allergic reaction and treating the complications. We have identified a need for specific medical interventions to accelerate wound regeneration. This approach has not previously been adopted in the management of TEN. We observed that in two cases of severe TEN, dramatic re-epithelialization and recovery coincided with the introduction of granulocyte colony-stimulating factor (G-CSF) for neutropenia. We explain how addition of the G-CSF promotes recovery from TEN by enhanced bioregeneration of the damaged tissues through accelerated re-epithelialization. G-CSF has been used for severe neutropenia in TEN, but we recommend and explain why, as in our Chelsea and Westminster protocol, G-CSF should be considered in treating severe TEN irrespective of the severity of neutropenia.

  5. Intranasal Delivery of Granulocyte Colony-Stimulating Factor Enhances Its Neuroprotective Effects Against Ischemic Brain Injury in Rats.

    Science.gov (United States)

    Sun, Bao-Liang; He, Mei-Qing; Han, Xiang-Yu; Sun, Jing-Yi; Yang, Ming-Feng; Yuan, Hui; Fan, Cun-Dong; Zhang, Shuai; Mao, Lei-Lei; Li, Da-Wei; Zhang, Zong-Yong; Zheng, Cheng-Bi; Yang, Xiao-Yi; Li, Yang V; Stetler, R Anne; Chen, Jun; Zhang, Feng

    2016-01-01

    Granulocyte colony-stimulating factor (G-CSF) is a hematopoietic growth factor with strong neuroprotective properties. However, it has limited capacity to cross the blood-brain barrier and thus potentially limiting its protective capacity. Recent studies demonstrated that intranasal drug administration is a promising way in delivering neuroprotective agents to the central nervous system. The current study therefore aimed at determining whether intranasal administration of G-CSF increases its delivery to the brain and its neuroprotective effect against ischemic brain injury. Transient focal cerebral ischemia in rat was induced with middle cerebral artery occlusion. Our resulted showed that intranasal administration is 8-12 times more effective than subcutaneous injection in delivering G-CSF to cerebrospinal fluid and brain parenchyma. Intranasal delivery enhanced the protective effects of G-CSF against ischemic injury in rats, indicated by decreased infarct volume and increased recovery of neurological function. The neuroprotective mechanisms of G-CSF involved enhanced upregulation of HO-1 and reduced calcium overload following ischemia. Intranasal G-CSF application also promoted angiogenesis and neurogenesis following brain ischemia. Taken together, G-CSF is a legitimate neuroprotective agent and intranasal administration of G-CSF is more effective in delivery and neuroprotection and could be a practical approach in clinic.

  6. Two protocols to treat thin endometrium with granulocyte colony-stimulating factor during frozen embryo transfer cycles.

    Science.gov (United States)

    Xu, Bin; Zhang, Qiong; Hao, Jie; Xu, Dabao; Li, Yanping

    2015-04-01

    The efficacy of two granulocyte colony-stimulating factor (G-CSF) protocols for thin endometrium were investigated. Eighty-two patients were diagnosed with thin endometrium (endometrial scratch subgroups. Compared with previous cycles, endometrial thickness increased from 5.7 ± 0.7 mm to 8.1 ± 2.1 mm after G-CSF treatment (P Endometrial thickness increases were not significantly different between the two subgroups. The G-CSF with endometrial scratch subgroup established nominally higher though non-significant clinical pregnancy and live birth rates than the G-CSF only subgroup (53.8 % versus 42.9% and 38.5% versus 28.6%, respectively). Fifty-two patients underwent FET despite edometrial thickness less than 7 mm, and were included as controls. Significantly higher embryo implantation and clinical pregnancy rates were observed in the G-CSF group compared with the control group (31.5% versus 13.9%; P Endometrial scracth did not impair G-CSF treatment for thin endometrium and favoured pregnancy and live birth rates. For patients with thin endometrium, embryo transfer cancellation and G-CSF treatment in subsequent FET cycles is beneficial. Copyright © 2014 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.

  7. Sarcoma granulocítico multicêntrico como recidiva de leucemia mieloide aguda Multicentric granulocytic sarcoma as relapse of acute myelogenous leukemia

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    Taciana G. S. Aguiar

    2009-01-01

    Full Text Available Sarcoma granulocítico (SG é um tumor sólido extramedular, constituído por células precursoras de granulócitos. É geralmente associado a leucemia mieloide aguda ou raramente a outras desordens mieloproliferativas. O tumor geralmente ocorre precedendo uma leucemia mieloide aguda, durante o seu curso ou após a remissão ter sido alcançada. O prognóstico é pobre e tem como principais modalidades terapêuticas a quimioterapia e a radioterapia. Relata- se um caso de SG multicêntrico, de evolução rápida, com acometimento difuso de pele, mamas, gânglios linfáticos, tecido celular subcutâneo e líquor, em mulher de 45 anos, fora de tratamento para leucemia mieloide aguda e em remissão hematológica há 18 meses. A paciente apresentava dor intensa em membro inferior direito há uma semana e estava em anticoagulação oral há seis meses por trombose venosa profunda neste membro. Diagnosticado o SG, a paciente foi tratada com radioterapia e quimioterapia com boa resposta. Após três meses de seguimento, em vigência do tratamento quimioterápico, evoluiu com recidiva do SG neste membro, associado ao acometimento das mamas e posteriormente do sistema nervoso central, evoluindo para óbito em aplasia e sepses.Granulocytic sarcoma is an extramedullary solid tumor consisting of immature granulocytic cells. It is often associated with acute myelogenous leukemia and more rarely with other myeloproliferative disorders. The tumor generally occurs before acute myeloid leukemia, during its course or after disease remission. It has a poor prognosis with the main therapeutic options being chemotherapy and radiotherapy. A multicentric accelerated case of granulocytic sarcoma of a 45- year- old woman with diffuse skin, breast, lymphatic ganglia and subcutaneous tissue presentations no longer undergoing treatment for acute myeloid leukemia and in hematologic remission for 18 months is reported. The patient presented with severe pain of right lower

  8. Infective Endocarditis

    Science.gov (United States)

    ... Venous Thromboembolism Aortic Aneurysm More Infective Endocarditis Updated:Mar 29,2018 View an illustration of endocarditis Infective ... procedure. Web Booklets on Congenital Heart Defects These online publications describe many defects and the procedures used ...

  9. MRSA Infection

    Science.gov (United States)

    ... to spread and sometimes become life-threatening. MRSA infections may affect your: Bloodstream Lungs Heart Bones Joints Prevention Preventing HA-MRSA In the hospital, people who are infected or colonized with MRSA ...

  10. Campylobacter Infections

    Science.gov (United States)

    Campylobacter infection is a common foodborne illness. You usually get it from eating contaminated food, especially raw ... You can also get it from drinking contaminated water or raw milk, or handling infected animal feces ( ...

  11. Staph Infections

    Science.gov (United States)

    ... Development Infections Diseases & Conditions Pregnancy & Baby Nutrition & Fitness Emotions & Behavior School & Family Life First Aid & Safety Doctors & ... infection. People with skin problems like burns or eczema may be more likely to get staph skin ...

  12. Rotavirus Infections

    Science.gov (United States)

    Rotavirus is a virus that causes gastroenteritis. Symptoms include severe diarrhea, vomiting, fever, and dehydration. Almost all ... the U.S. are likely to be infected with rotavirus before their 5th birthday. Infections happen most often ...

  13. Infection of endothelial cells by common human viruses.

    Science.gov (United States)

    Friedman, H M

    1989-01-01

    Common human viruses were evaluated for their ability to replicate in the endothelial cells of human umbilical vein and bovine thoracic aorta in vitro. Infection occurred with most viruses. The susceptibilities of endothelial cells derived from bovine aorta, pulmonary artery, and vena cava were compared. Among the viruses studied, no differences were noted in the ability to grow in endothelial cells from these three large vessels. One virus, herpes simplex virus type 1, was evaluated for its ability to produce persistent infection of endothelial cells. Infection developed and persisted for up to 3 months. After the first week, productive infection was found in less than 1% of cells. Nevertheless, the infection markedly affected the growth and morphology of the endothelial monolayer. Infection with any of several different viruses was noted to alter endothelial cell functions, including adherence of granulocytes, production of colony-stimulating factor, and synthesis of matrix protein. In addition, herpes simplex virus type 1 induced receptors for the Fc portion of IgG and for complement component C3b. These findings indicate that common human viruses can profoundly affect the biology of the endothelium.

  14. Novel Babesia and Hepatozoon agents infecting non-volant small mammals in the Brazilian Pantanal, with the first record of the tick Ornithodoros guaporensis in Brazil.

    Science.gov (United States)

    Wolf, Rafael William; Aragona, Mônica; Muñoz-Leal, Sebastián; Pinto, Leticia Borges; Melo, Andréia Lima Tomé; Braga, Isis Assis; Costa, Jackeliny dos Santos; Martins, Thiago Fernandes; Marcili, Arlei; Pacheco, Richard de Campos; Labruna, Marcelo B; Aguiar, Daniel Moura

    2016-04-01

    Taking into account the diversity of small terrestrial mammals of the Pantanal, the present study aimed to verify the occurrence of infection by Ehrlichia spp., Anaplasma spp., Rickettsia spp., Hepatozoon spp., Babesia spp. and parasitism by ticks in non-volant small mammals collected in the Brazilian Pantanal. Samples of blood, liver and spleen were collected from 64 captured animals, 22 marsupials and 42 rodents. Pathogen detection was performed by the use of genus-specific Polymerase Chain Reaction (PCR) assays. Ticks collected from the animals consisted of Amblyomma sculptum and Amblyomma triste nymphs, and Ornithodoros guaporensis larvae. None of the vertebrate samples (blood, liver, or spleen) yielded detectable DNA of Rickettsia spp. or Ehrlichia spp. The blood of the rodent Hylaeamys megacephalus yielded an Anaplasma sp. genotype (partial 16S rRNA gene) 99% similar to multiple Anaplasma spp. genotypes around the world. The blood of three rodents of the species Calomys callosus were positive for a novel Hepatozoon sp. agent, phylogenetically related (18S rDNA gene) to distinct Hepatozoon genotypes that have been detected in rodents from different parts of the world. One marsupial (Monodelphis domestica) and three rodents (Thrichomys pachyurus) were positive to novel piroplasmid genotypes, phylogenetically (18S rDNA gene) related to Theileria bicornis, Cytauxzoon manul, and Cytauxzoon felis. The present study provides the first molecular detection of Hepatozoon sp. and piroplasmids in small mammals in Brazil. Additionally, we expanded the distribution of O. guaporensis to Brazil, since this tick species was previously known to occur only in Bolivia. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. Shigella Infections

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Shigella Infections KidsHealth / For Parents / Shigella Infections What's in ... Doctor Print en español Infecciones por Shigella About Shigella Shigella are bacteria that can infect the digestive ...

  16. Relative uptake of technetium 99m stannous colloid by neutrophils and monocytes is altered by gram-negative infection

    International Nuclear Information System (INIS)

    Ramsay, Stuart C.; Maggs, Jacqueline A.; Ketheesan, Natkunam; Norton, Robert; LaBrooy, Justin

    2005-01-01

    Gram-negative infection alters phagocytic cell function; hence, it could affect phagocytic uptake of inorganic colloids by these cells. Neutrophil and monocyte uptake of technetium 99m stannous colloid ( 99m Tc SnC) in whole blood was measured in 10 patients with gram-negative infection (Burkholderia pseudomallei) and 7 controls. Mean uptake per individual neutrophil was reduced in infection. Uptake per monocyte was not significantly different. Blood from six normal individuals was incubated with lysed B. pseudomallei and colloid, which showed reduced neutrophil uptake, but increased monocyte uptake. These results indicate that uptake of 99m Tc SnC stannous colloid can be used to measure alteration in phagocytic cell function. They suggest that infection with B. pseudomallei is associated with reduced phagocytosis by individual neutrophils, possibly through toxic effects of bacterial products. This could have immunopathogenic consequences for this gram-negative infection and may explain why it responds to granulocyte colony-stimulating factor

  17. Human papillomavirus infection is associated with decreased levels of GM-CSF in cervico-vaginal fluid of infected women.

    Science.gov (United States)

    Comar, Manola; Monasta, Lorenzo; Zanotta, Nunzia; Vecchi Brumatti, Liza; Ricci, Giuseppe; Zauli, Giorgio

    2013-10-01

    Although human papillomavirus (HPV) is the most common sexually transmitted infection, there are very scant data about the influence of this virus on the in vitro fertilization outcome. To assess the presence of HPV in the cervico-vaginal fluid in relationship to the in vitro fertilization (IVF) outcome and to the concentration of selected cytokines, known to affect embryo implantation and gestation: granulocyte-macrophage colony stimulating factor (GM-CSF) and granulocyte colony stimulating factor (G-CSF). Cervico-vaginal samples were collected on the day of oocyte pick-up from 82 women. Vaginas were flushed with 50 mL of sterile water and 3 mL of fluid was collected. Twelve women (15%) were positive for HPV. Interestingly, among HPV(+) women live birth rate was about half of the rate in HPV(-) women, although the differences were not statistically significant due to the low number of cases. Cervico-vaginal samples of a sub-group of 29 (8 HPV(+) and 21 HPV(-)) women were analyzed for GM-CSF and G-CSF by ELISA. GM-CSF but not G-CSF was significantly lower in the cervico-vaginal fluid of HPV(+) than in HPV(-) women. Since GM-CSF plays an important role during pregnancy, the reduced levels of GM-CSF in the cervico-vaginal fluid of HPV(+) women might contribute to explain the reduced live birth rate observed in HPV(+) women. Copyright © 2013 Elsevier B.V. All rights reserved.

  18. Granulocyte colony-stimulating factors for febrile neutropenia prophylaxis following chemotherapy: systematic review and meta-analysis

    Directory of Open Access Journals (Sweden)

    Stevenson Matt D

    2011-09-01

    Full Text Available Abstract Background Febrile neutropenia (FN occurs following myelosuppressive chemotherapy and is associated with morbidity, mortality, costs, and chemotherapy reductions and delays. Granulocyte colony-stimulating factors (G-CSFs stimulate neutrophil production and may reduce FN incidence when given prophylactically following chemotherapy. Methods A systematic review and meta-analysis assessed the effectiveness of G-CSFs (pegfilgrastim, filgrastim or lenograstim in reducing FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. G-CSFs were compared with no primary G-CSF prophylaxis and with one another. Nine databases were searched in December 2009. Meta-analysis used a random effects model due to heterogeneity. Results Twenty studies compared primary G-CSF prophylaxis with no primary G-CSF prophylaxis: five studies of pegfilgrastim; ten of filgrastim; and five of lenograstim. All three G-CSFs significantly reduced FN incidence, with relative risks of 0.30 (95% CI: 0.14 to 0.65 for pegfilgrastim, 0.57 (95% CI: 0.48 to 0.69 for filgrastim, and 0.62 (95% CI: 0.44 to 0.88 for lenograstim. Overall, the relative risk of FN for any primary G-CSF prophylaxis versus no primary G-CSF prophylaxis was 0.51 (95% CI: 0.41 to 0.62. In terms of comparisons between different G-CSFs, five studies compared pegfilgrastim with filgrastim. FN incidence was significantly lower for pegfilgrastim than filgrastim, with a relative risk of 0.66 (95% CI: 0.44 to 0.98. Conclusions Primary prophylaxis with G-CSFs significantly reduces FN incidence in adults undergoing chemotherapy for solid tumours or lymphoma. Pegfilgrastim reduces FN incidence to a significantly greater extent than filgrastim.

  19. Kinetics of granulocytic and erythroid progenitor cells are affected differently by short-term, low-level benzene exposure

    Energy Technology Data Exchange (ETDEWEB)

    Dempster, A.M.; Snyder, C.A. (New York Univ. Medical Center, NY (United States). Inst. of Environmental Medicine)

    1991-09-01

    Mice were exposed to either air or 10 ppm benzene for 6 h/d X 5 d. Immediately after the last exposure, mice were injected, i.v., with either saline or hydroxyurea (HU). The dose of HU was sufficient to kill hematopoietic cells in or near S-phase of the cell cycle and sufficient to synchronize the surviving populations of hematopoietic cells. Three days after benzene exposure, CFU-E numbers had declined to 50% of control values while CFU-GM numbers were equal to control values at this time. The benzene exposures were sufficient to double the percentage of CFU-E in S-phase but produced no such increase among CFU-Gm. During 3 days of recovery from benzene exposure and HU treatment, the CFU-E population expanded 30-fold while the CFU-GM population expanded less than 3-fold. Following benzene exposure and HU treatment, both progenitor cells produced elevated numbers of their respective progeny. When CFU-E from benzene-exposed mice were cultured with varying concentrations of erythropoietin (EPO), the response at maximal EPO concentration was 66% of the response by control CFU-E. This strongly suggests that the CFU-E populations from benzene-exposed mice had been depleted of cells in or near S-phase. The results indicate that CFU-GM respond to low-level benzene exposure by increasing their rate of differentiation but not their rate of proliferation, while CFU-E respond by increasing both their rates of differentiation and proliferation. We speculate that it is the increase in CFU-E proliferation that renders these cells more susceptible to benzene than their granulocytic counterparts, especially those CFU-E at or near the S-phase of the cell cycle. (orig.).

  20. Benefits of gene transduction of granulocyte macrophage colony-stimulating factor in cancer vaccine using genetically modified dendritic cells.

    Science.gov (United States)

    Ojima, Toshiyasu; Iwahashi, Makoto; Nakamura, Masaki; Matsuda, Kenji; Nakamori, Mikihito; Ueda, Kentaro; Naka, Teiji; Katsuda, Masahiro; Miyazawa, Motoki; Yamaue, Hiroki

    2007-10-01

    Granulocyte macrophage colony-stimulating factor (GM-CSF) is a key cytokine for the generation and stimulation of dendritic cells (DCs), and it may also play a pivotal role in promoting the survival of DCs. In this study, the feasibility of creating a cancer vaccine using DCs adenovirally transduced with the carcinoembryonic antigen (CEA) gene and the GM-CSF gene was examined. In addition, the effect of the co-transduction of GM-CSF gene on the lifespan of these genetically modified DCs was determined. A cytotoxic assay using peripheral blood mononuclear cell (PBMC)-derived cytotoxic T lymphocytes (CTLs) was performed in a 4-h 51Cr release assay. The apoptosis of DCs was examined by TdT-mediated dUTP-FITC nick end labeling (TUNEL) assay. CEA-specific CTLs were generated from PBMCs stimulated with genetically modified DCs expressing CEA. The cytotoxicity of these CTLs was augmented by co-transduction of DCs with the GM-CSF gene. Co-transduction of the GM-CSF gene into DCs inhibited apoptosis of these DCs themselves via up-regulation of Bcl-x(L) expression, leading to the extension of the lifespan of these DCs. Furthermore, the transduction of the GM-CSF gene into DCs also suppressed the incidence of apoptosis of DCs induced by transforming growth factor-beta1 (TGFbeta-1). Immunotherapy using these genetically modified DCs may therefore be useful with several advantages as follows: i) adenoviral toxicity to DCs can be reduced; ii) the lifespan of vaccinated DCs can be prolonged; and iii) GM-CSF may protect DCs from apoptosis induced by tumor-derived TGFbeta-1 in the regional lymph nodes.

  1. Integrated FDG-PET/CT for detection, therapy monitoring and follow-up of granulocytic sarcoma. Initial results

    Energy Technology Data Exchange (ETDEWEB)

    Aschoff, Philip; Werner, M.K.; Lichy, M.; Pfannenberg, C. [Dept. of Diagnostic and Interventional Radiology, Univ. Hospital, Eberhard-Karls-Univ. Tuebingen (Germany); Haentschel, M.; Vogel, W. [Dept. of Internal Medicine, Univ. Hospital, Eberhard-Karls-Univ. Tuebingen (Germany); Oeksuez, M. [Dept. of Nuclear Medicine, Univ. Hospital, Eberhard-Karls-Univ. Tuebingen (Germany)

    2009-07-01

    Granulocytic sarcomas (GS) are rare extramedullary manifestations of myeloid or lymphoblastic leukaemia. Laboratory examinations are of limited use for diagnosis of extramedullary disease. Radiological imaging based on morphology is challenging. To date, the possible role of FDG-PET/CT as a method for combined metabolic and morphologic imaging is unclear. We present a series of 10 patients to evaluate the potential role of FDG-PET/CT in the management of GS. Patients, materials, methods: a retrospective evaluation of 18 FDG-PET/CT exams in 10 patients with histologically proven GS was performed. All scans included a contrast enhanced CT. The FDG uptake of GS was analyzed and the sensitivity of lesion detection was compared to PET and CT alone. The changes in FDG uptake after therapy were compared to morphological changes detected by CT and follow-up/clinical outcome. Results: 52 untreated or recurrent GS lesions were detected by FDG-PET/CT and all showed an increased FDG uptake with a mean SUVmax and SUVavg of 5.1 and 3.4, respectively. GS was multifocal in 8/10 patients. Combined PET/CT avoided 5 false positive findings compared to PET alone and 13 false negative findings and 1 false positive compared to CT alone. Changes in FDG uptake after therapy correlated with clinical outcome and were more reliable than CT assessment alone. PET/CT identified recurrent GS in 3 patients. Conclusion: viable GS are FDG-avid. Using this metabolic information and morphologic CT criteria, combined FDG-PET/CT was more accurate in lesion detection than FDG-PET or CT alone. Changes in FDG uptake after therapy might be a useful additional parameter for therapy monitoring. Therefore, FDG-PET/CU appears to be a promising diagnostic and monitoring tool in the management of patients with GS. (orig.)

  2. Annual patient and caregiver burden of oncology clinic visits for granulocyte-colony stimulating factor therapy in the US.

    Science.gov (United States)

    Stephens, J Mark; Li, Xiaoyan; Reiner, Maureen; Tzivelekis, Spiros

    2016-01-01

    Prophylactic treatment with granulocyte-colony stimulating factors (G-CSFs) is indicated for chemotherapy patients with a significant risk of febrile neutropenia. This study estimates the annual economic burden on patients and caregivers of clinic visits for prophylactic G-CSF injections in the US. Annual clinic visits for prophylactic G-CSF injections (all cancers) were estimated from national cancer incidence, chemotherapy treatment and G-CSF utilization data, and G-CSF sales and pricing information. Patient travel times, plus time spent in the clinic, were estimated from patient survey responses collected during a large prospective cohort study (the Prospective Study of the Relationship between Chemotherapy Dose Intensity and Mortality in Early-Stage (I-III) Breast Cancer Patients). Economic models were created to estimate travel costs, patient co-pays and the economic value of time spent by patients and caregivers in G-CSF clinic visits. Estimated total clinic visits for prophylactic G-CSF injections in the US were 1.713 million for 2015. Mean (SD) travel time per visit was 62 (50) min; mean (SD) time in the clinic was 41 (68) min. Total annual time for travel to and from the clinic, plus time at the clinic, is estimated at 4.9 million hours, with patient and caregiver time valued at $91.8 million ($228 per patient). The estimated cumulative annual travel distance for G-CSF visits is 60.2 million miles, with a total transportation cost of $28.9 million ($72 per patient). Estimated patient co-pays were $61.1 million, ∼$36 per visit, $152 per patient. The total yearly economic impact on patients and caregivers is $182 million, ∼$450 per patient. Data to support model parameters were limited. Study estimates are sensitive to the assumptions used. The burden of clinic visits for G-CSF therapy is a significant addition to the total economic burden borne by cancer patients and their families.

  3. Granulocyte-colony stimulating factor and umbilical cord blood cell transplantation: Synergistic therapies for the treatment of traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Michael G Liska

    2017-01-01

    Full Text Available Traumatic brain injury (TBI is now characterized as a progressive, degenerative disease and continues to stand as a prevalent cause of death and disability. The pathophysiology of TBI is complex, with a variety of secondary cell death pathways occurring which may persist chronically following the initial cerebral insult. Current therapeutic options for TBI are minimal, with surgical intervention or rehabilitation therapy existing as the only viable treatments. Considering the success of stem-cell therapies in various other neurological diseases, their use has been proposed as a potential potent therapy for patients suffering TBI. Moreover, stem cells are highly amenable to adjunctive use with other therapies, providing an opportunity to overcome the inherent limitations of using a single therapeutic agent. Our research has verified this additive potential by demonstrating the efficacy of co-delivering human umbilical cord blood (hUCB cells with granulocyte-colony stimulating factor (G-CSF in a murine model of TBI, providing encouraging results which support the potential of this approach to treat patients suffering from TBI. These findings justify ongoing research toward uncovering the mechanisms which underlie the functional improvements exhibited by hUCB + G-CSF combination therapy, thereby facilitating its safe and effect transition into the clinic. This paper is a review article. Referred literature in this paper has been listed in the reference section. The datasets supporting the conclusions of this article are available online by searching various databases, including PubMed. Some original points in this article come from the laboratory practice in our research center and the authors' experiences.

  4. Chimeric HIV-1 Envelope Glycoproteins with Potent Intrinsic Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) Activity*

    Science.gov (United States)

    Boot, Maikel; Cobos Jiménez, Viviana; Kootstra, Neeltje A.; Sanders, Rogier W.

    2013-01-01

    HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs) that target the envelope glycoprotein complex (Env). An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF) domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed EnvGM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized EnvGM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric EnvGM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins. PMID:23565193

  5. Characterization and molecular features of the cell surface receptor for human granulocyte-macrophage colony-stimulating factor

    International Nuclear Information System (INIS)

    Chiba, S.; Tojo, A.; Kitamura, T.; Urabe, A.; Miyazono, K.; Takaku, F.

    1990-01-01

    The receptors for human granulocyte-macrophage colony-stimulating factor (GM-CSF) on the surfaces of normal and leukemic myeloid cells were characterized using 125I-labeled bacterially synthesized GM-CSF. The binding was rapid, specific, time dependent, and saturable. Scatchard analysis of the 125I-GM-CSF binding to peripheral blood neutrophils indicated the presence of a single class of binding site (Kd = 99 +/- 21 pM; 2,304 +/- 953 sites/cell). However, for peripheral blood monocytes and two GM-CSF-responsive myeloid cell lines (U-937 and TF-1), the Scatchard plots were biphasic curvilinear, which were best fit by curves derived from two binding site model: one with high affinity (Kd1 = 10-40 pM) and the other with low affinity (Kd2 = 0.9-2.0 nM). For U-937 cells, the number of high-affinity receptors was 1,058 +/- 402 sites/cell and that of low-affinity receptors was estimated to be 10,834 +/- 2,396 sites/cell. Cross-linking studies yielded three major bands with molecular masses of 150 kDa, 115 kDa, and 95 kDa, which were displaced by an excess amount of unlabeled GM-CSF, suggesting 135-kDa, 100-kDa, and 80-kDa species for the individual components of the human GM-CSF receptor. These bands comigrated for different cell types including peripheral blood neutrophils, U-937 cells and TF-1 cells. In experiments using U-937 cells, only the latter two bands appeared to be labeled in a dose-dependent manner in a low-affinity state. These results suggest that the human GM-CSF receptor possibly forms a multichain complex

  6. Granulocyte-colony-stimulating factor (G-CSF) signaling in spinal microglia drives visceral sensitization following colitis.

    Science.gov (United States)

    Basso, Lilian; Lapointe, Tamia K; Iftinca, Mircea; Marsters, Candace; Hollenberg, Morley D; Kurrasch, Deborah M; Altier, Christophe

    2017-10-17

    Pain is a main symptom of inflammatory diseases and often persists beyond clinical remission. Although we have a good understanding of the mechanisms of sensitization at the periphery during inflammation, little is known about the mediators that drive central sensitization. Recent reports have identified hematopoietic colony-stimulating factors as important regulators of tumor- and nerve injury-associated pain. Using a mouse model of colitis, we identify the proinflammatory cytokine granulocyte-colony-stimulating factor (G-CSF or Csf-3) as a key mediator of visceral sensitization. We report that G-CSF is specifically up-regulated in the thoracolumbar spinal cord of colitis-affected mice. Our results show that resident spinal microglia express the G-CSF receptor and that G-CSF signaling mediates microglial activation following colitis. Furthermore, healthy mice subjected to intrathecal injection of G-CSF exhibit pronounced visceral hypersensitivity, an effect that is abolished by microglial depletion. Mechanistically, we demonstrate that G-CSF injection increases Cathepsin S activity in spinal cord tissues. When cocultured with microglia BV-2 cells exposed to G-CSF, dorsal root ganglion (DRG) nociceptors become hyperexcitable. Blocking CX3CR1 or nitric oxide production during G-CSF treatment reduces excitability and G-CSF-induced visceral pain in vivo. Finally, administration of G-CSF-neutralizing antibody can prevent the establishment of persistent visceral pain postcolitis. Overall, our work uncovers a DRG neuron-microglia interaction that responds to G-CSF by engaging Cathepsin S-CX3CR1-inducible NOS signaling. This interaction represents a central step in visceral sensitization following colonic inflammation, thereby identifying spinal G-CSF as a target for treating chronic abdominal pain.

  7. Chimeric HIV-1 envelope glycoproteins with potent intrinsic granulocyte-macrophage colony-stimulating factor (GM-CSF activity.

    Directory of Open Access Journals (Sweden)

    Gözde Isik

    Full Text Available HIV-1 acquisition can be prevented by broadly neutralizing antibodies (BrNAbs that target the envelope glycoprotein complex (Env. An ideal vaccine should therefore be able to induce BrNAbs that can provide immunity over a prolonged period of time, but the low intrinsic immunogenicity of HIV-1 Env makes the elicitation of such BrNAbs challenging. Co-stimulatory molecules can increase the immunogenicity of Env and we have engineered a soluble chimeric Env trimer with an embedded granulocyte-macrophage colony-stimulating factor (GM-CSF domain. This chimeric molecule induced enhanced B and helper T cell responses in mice compared to Env without GM-CSF. We studied whether we could optimize the activity of the embedded GM-CSF as well as the antigenic structure of the Env component of the chimeric molecule. We assessed the effect of truncating GM-CSF, removing glycosylation-sites in GM-CSF, and adjusting the linker length between GM-CSF and Env. One of our designed Env(GM-CSF chimeras improved GM-CSF-dependent cell proliferation by 6-fold, reaching the same activity as soluble recombinant GM-CSF. In addition, we incorporated GM-CSF into a cleavable Env trimer and found that insertion of GM-CSF did not compromise Env cleavage, while Env cleavage did not compromise GM-CSF activity. Importantly, these optimized Env(GM-CSF proteins were able to differentiate human monocytes into cells with a macrophage-like phenotype. Chimeric Env(GM-CSF should be useful for improving humoral immunity against HIV-1 and these studies should inform the design of other chimeric proteins.

  8. Granulocyte-macrophage colony-stimulating factor primes interleukin-13 production by macrophages via protease-activated receptor-2.

    Science.gov (United States)

    Aoki, Manabu; Yamaguchi, Rui; Yamamoto, Takatoshi; Ishimaru, Yasuji; Ono, Tomomichi; Sakamoto, Arisa; Narahara, Shinji; Sugiuchi, Hiroyuki; Hirose, Eiji; Yamaguchi, Yasuo

    2015-04-01

    Chronic inflammation is often linked to the presence of type 2-polarized macrophages, which are induced by the T helper type 2 cytokines interleukin-4 and interleukin-13 (IL-13). IL-13 is a key mediator of tissue fibrosis caused by T helper type 2-based inflammation. Human neutrophil elastase (HNE) plays a pivotal role in the pathogenesis of pulmonary fibrosis. This study investigated the priming effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on IL-13 expression by macrophages stimulated with HNE. Adherent macrophages were obtained from primary cultures of human mononuclear cells. Expression of IL-13 mRNA and protein by GM-CSF-dependent macrophages was investigated after stimulation with HNE, using the polymerase chain reaction and enzyme-linked immunosorbent assay. GM-CSF had a priming effect on IL-13 mRNA and protein expression by macrophages stimulated with HNE, while this effect was not observed for various other cytokines. GM-CSF-dependent macrophages showed a significant increase in the expression of protease activated receptor-2 (PAR-2) mRNA and protein. The response of IL-13 mRNA to HNE was significantly decreased by pretreatment with alpha1-antitrypsin, a PAR-2 antibody (SAM11), or a PAR-2 antagonist (ENMD-1068). These findings suggest that stimulation with HNE can induce IL-13 production by macrophages, especially GM-CSF-dependent macrophages. Accordingly, neutrophil elastase may have a key role in fibrosis associated with chronic inflammation. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. The combined effect of erythropoietin and granulocyte macrophage colony stimulating factor on liver regeneration after major hepatectomy in rats

    Directory of Open Access Journals (Sweden)

    Frangou Matrona

    2010-07-01

    Full Text Available Abstract Background The liver presents a remarkable capacity for regeneration after hepatectomy but the exact mechanisms and mediators involved are not yet fully clarified. Erythropoietin (EPO and Granulocyte-Macrophage Colony Stimulating Factor (GM-CSF have been shown to promote liver regeneration after major hepatectomy. Aim of this experimental study is to compare the impact of exogenous administration of EPO, GM-CSF, as well as their combination on the promotion of liver regeneration after major hepatectomy. Methods Wistar rats were submitted to 70% major hepatectomy. The animals were assigned to 4 experimental groups: a control group (n = 21 that received normal saline, an EPO group (n = 21, that received EPO 500 IU/kg, a GM-CSF group (n = 21 that received 20 mcg/kg of GM-CSF and a EPO+GMCSF group (n = 21 which received a combination of the above. Seven animals of each group were killed on the 1st, 3rd and 7th postoperative day and their remnant liver was removed to evaluate liver regeneration by immunochemistry for PCNA and Ki 67. Results Our data suggest that EPO and GM-CSF increases liver regeneration following major hepatectomy when administered perioperatively. EPO has a more significant effect than GM-CSF (p Conclusion EPO, GM-CSF and their combination enhance liver regeneration after hepatectomy in rats when administered perioperatively. However their combination has a weaker effect on liver regeneration compared to EPO alone. Further investigation is needed to assess the exact mechanisms that mediate this finding.

  10. Purity assessment of recombinant human granulocyte colony-stimulating factor in finished drug product by capillary zone electrophoresis.

    Science.gov (United States)

    Benković, Goran; Skrlin, Ana; Madić, Tomislav; Debeljak, Zeljko; Medić-Šarić, Marica

    2014-09-01

    Current methods for determination of impurities with different charge-to-volume ratio are limited especially in terms of sensitivity and precision. The main goal of this research was to establish a quantitative method for determination of impurities with charges differing from that of recombinant human granulocyte colony-stimulating factor (rhG-CSF, filgrastim) with superior precision and sensitivity compared to existing methods. A CZE method has been developed, optimized, and validated for a purity assessment of filgrastim in liquid pharmaceutical formulations. Optimal separation of filgrastim from the related impurities with different charges was achieved on a 50 μm id fused-silica capillary of a total length of 80.5 cm. A BGE that contains 100 mM phosphoric acid adjusted to pH 7.0 with triethanolamine was used. The applied voltage was 20 kV while the temperature was maintained at 25°C. UV detection was set to 200 nm. Method was validated in terms of selectivity/specificity, linearity, precision, LOD, LOQ, stability, and robustness. Linearity was observed in the concentration range of 6-600 μg/mL and the LOQ was determined to be 0.3% relative to the concentration of filgrastim of 0.6 mg/mL. Other validation parameters were also found to be acceptable; thus the method was successfully applied for a quantitative purity assessment of filgrastim in a finished drug product. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. Thermal sensitivity and thermally enhanced radiosensitivity of murine bone marrow granulocyte-macrophage colony-forming units (CFU-GM)

    International Nuclear Information System (INIS)

    Yoshida, Hiroshi

    1994-01-01

    This study was to evaluate thermal response of granulocyte-macrophage colony-forming unit (CFU-GM) in vitro and to investigate the difference of thermally enhanced radiosensitivity on cell survivals of CFU-GM between in vitro and in vivo. In in vitro heating exposure, bone marrow suspensions, obtained from mouse femora or tibiae, were incubated; and in vivo heating exposure, the lower half-body of mice were immersed in a circulating hot water bath. For irradiation schedules, cell suspensions were irradiated in vitro or in vivo (whole-body irradiation). Thermal sensitivity curve, obtained by in vivo heating exposure, showed a shoulder region at short exposures followed by an exponential decline during longer heating exposures. The Arrhenius curve showed a break at 42.3deg C and inactivation enthalpy was 1836 kJ/mol (438 kcal/mole) below the break point and 704 kJ/mole (168 kcal/mole) above the point. When bone marrow suspensions, obtained after either in vitro or in vivo irradiation, were heated in vitro at 42deg C for 60 min, supura-additive effect on cell survivals was observed by in vivo irradiation, but not observed by in vitro irradiation. Thermal enhancement ratio (TER), defined as D 0 of combined in vivo irradiation and in vitro heating divided by D 0 of the sole in vivo irradiation, was 1.12. In vivo heating following in vivo irradiation also showed supra-additive effect, giving TER of 1.66. These findings indicated that murine marrow CFU-GM is sensitive to hyperthermia and that thermal radiosensitization is never negligible when hyperthermia is employed with preceding X-irradiation. Thus, combined use of radiotherapy and hyperthermia may decrease bone marrow function. (N.K.)

  12. Is febrile neutropenia prophylaxis with granulocyte-colony stimulating factors economically justified for adjuvant TC chemotherapy in breast cancer?

    Science.gov (United States)

    Skedgel, Chris; Rayson, Daniel; Younis, Tallal

    2016-01-01

    Febrile neutropenia (FN) during adjuvant chemotherapy is associated with morbidity, mortality risk, and substantial cost, and subsequent chemotherapy dose reductions may result in poorer outcomes. Patients at high risk of, or who develop FN, often receive prophylaxis with granulocyte colony-stimulating factors (G-CSF). We investigated whether different prophylaxis strategies with G-CSF offered favorable value-for-money. We developed a decision model to estimate the short- and long-term costs and outcomes of a hypothetical cohort of women with breast cancer receiving adjuvant taxotere + cyclophosphamide (TC) chemotherapy. The short-term phase estimated upfront costs and FN risks with adjuvant TC chemotherapy without G-CSF prophylaxis (i.e., chemotherapy dose reductions) as well as with secondary and primary G-CSF prophylaxis strategies. The long-term phase estimated the expected costs and quality-adjusted life years (QALYs) for patients who completed adjuvant TC chemotherapy with or without one or more episodes of FN. Secondary G-CSF was associated with lower costs and greater QALY gains than a no G-CSF strategy. Primary G-CSF appears likely to be cost-effective relative to secondary G-CSF at FN rates greater than 28%, assuming some loss of chemotherapy efficacy at lower dose intensities. The cost-effectiveness of primary vs. secondary G-CSF was sensitive to FN risk and mortality, and loss of chemotherapy efficacy following FN. Secondary G-CSF is more effective and less costly than a no G-CSF strategy. Primary G-CSF may be justified at higher willingness-to-pay thresholds and/or higher FN risks, but this threshold FN risk appears to be higher than the 20% rate recommended by current clinical guidelines.

  13. Cost-benefit analysis of prophylactic granulocyte colony-stimulating factor during CHOP antineoplastic therapy for non-Hodgkin's lymphoma.

    Science.gov (United States)

    Dranitsaris, G; Altmayer, C; Quirt, I

    1997-06-01

    Several randomised comparative trials have shown that granulocyte colony-stimulating factor (G-CSF) reduces the duration of neutropenia, hospitalisation and intravenous antibacterial use in patients with cancer who are receiving high-dosage antineoplastic therapy. However, one area that has received less attention is the role of G-CSF in standard-dosage antineoplastic regimens. One such treatment that is considered to have a low potential for inducing fever and neutropenia is the CHOP regimen (cyclophosphamide, doxorubicin, vincristine and prednisone) for non-Hodgkin's lymphoma. We conducted a cost-benefit analysis from a societal perspective in order to estimate the net cost or benefit of prophylactic G-CSF in this patient population. This included direct costs for hospitalisation with antibacterial support, as well as indirect societal costs, such as time off work and antineoplastic therapy delays secondary to neutropenia. The findings were then tested by a comprehensive sensitivity analysis. The administration of G-CSF at a dosage of 5 micrograms/kg/day for 11 doses following CHOP resulted in an overall net cost of $Can1257. In the sensitivity analysis, lowering the G-CSF dosage to 2 micrograms/kg/day generated a net benefit of $Can6564, indicating a situation that was cost saving to society. The results of the current study suggest that the use of G-CSF in patients receiving CHOP antineoplastic therapy produces a situation that is close to achieving cost neutrality. However, low-dosage (2 micrograms/kg/day) G-CSF is an economically attractive treatment strategy because it may result in overall savings to society.

  14. Notch signaling mediates granulocyte-macrophage colony-stimulating factor priming-induced transendothelial migration of human eosinophils.

    Science.gov (United States)

    Liu, L Y; Wang, H; Xenakis, J J; Spencer, L A

    2015-07-01

    Priming with cytokines such as granulocyte-macrophage colony-stimulating factor (GM-CSF) enhances eosinophil migration and exacerbates the excessive accumulation of eosinophils within the bronchial mucosa of asthmatics. However, mechanisms that drive GM-CSF priming are incompletely understood. Notch signaling is an evolutionarily conserved pathway that regulates cellular processes, including migration, by integrating exogenous and cell-intrinsic cues. This study investigates the hypothesis that the priming-induced enhanced migration of human eosinophils requires the Notch signaling pathway. Using pan Notch inhibitors and newly developed human antibodies that specifically neutralize Notch receptor 1 activation, we investigated a role for Notch signaling in GM-CSF-primed transmigration of human blood eosinophils in vitro and in the airway accumulation of mouse eosinophils in vivo. Notch receptor 1 was constitutively active in freshly isolated human blood eosinophils, and inhibition of Notch signaling or specific blockade of Notch receptor 1 activation during GM-CSF priming impaired priming-enhanced eosinophil transendothelial migration in vitro. Inclusion of Notch signaling inhibitors during priming was associated with diminished ERK phosphorylation, and ERK-MAPK activation was required for GM-CSF priming-induced transmigration. In vivo in mice, eosinophil accumulation within allergic airways was impaired following systemic treatment with Notch inhibitor, or adoptive transfer of eosinophils treated ex vivo with Notch inhibitor. These data identify Notch signaling as an intrinsic pathway central to GM-CSF priming-induced eosinophil tissue migration. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Addition of Granulocyte/Monocyte Apheresis to Oral Prednisone for Steroid-dependent Ulcerative Colitis: A Randomized Multicentre Clinical Trial.

    Science.gov (United States)

    Domènech, Eugeni; Panés, Julián; Hinojosa, Joaquín; Annese, Vito; Magro, Fernando; Sturniolo, Giacomo Carlo; Bossa, Fabrizio; Fernández, Francisco; González-Conde, Benito; García-Sánchez, Valle; Dignass, Axel; Herrera, José Manuel; Cabriada, José Luis; Guardiola, Jordi; Vecchi, Maurizio; Portela, Francisco; Ginard, Daniel

    2018-05-25

    Steroid-dependency occurs in up to 30% of patients with ulcerative colitis [UC]. In this setting, few drugs have demonstrated efficacy in inducing steroid-free remission. The aim of this study was to evaluate the efficacy and safety of adding granulocyte/monocyte apheresis [GMA] to oral prednisone in patients with steroid-dependent UC. This was a randomized, multicentre, open trial comparing 7 weekly sessions of GMA plus oral prednisone [40 mg/day and tapering] with prednisone alone, in patients with active, steroid-dependent UC [Mayo score 4-10 and inability to withdraw corticosteroids in 3 months or relapse within the first 3 months after discontinuation]. Patients were stratified by concomitant use of thiopurines at inclusion. A 9-week tapering schedule of prednisone was pre-established in both study groups. The primary endpoint was steroid-free remission [defined as a total Mayo score ≤2, with no subscore >1] at Week 24, with no re-introduction of corticosteroids. In all 123 patients were included [63 GMA group, 62 prednisone alone]. In the intention-to-treat analysis, steroid-free remission at Week 24 was achieved in 13% (95% confidence interval [CI] 6-24) in the GMA group and 7% [95% CI 2-16] in the control group [p = 0.11]. In the GMA group, time to relapse was significantly longer (hazard ratio [HR] 1.7 [1.16-2.48], P = 0.005) and steroid-related adverse events were significantly lower [6% vs 20%, P < 0.05]. In a randomized trial, the addition of 7 weekly sessions of GMA to a conventional course of oral prednisone did not increase the proportion of steroid-free remissions in patients with active steroid-dependent UC, though it delayed clinical relapse.

  16. Adrenaline administration promotes the efficiency of granulocyte colony stimulating factor-mediated hematopoietic stem and progenitor cell mobilization in mice.

    Science.gov (United States)

    Chen, Chong; Cao, Jiang; Song, Xuguang; Zeng, Lingyu; Li, Zhenyu; Li, Yong; Xu, Kailin

    2013-01-01

    A high dose of granulocyte colony stimulating factor (G-CSF) is widely used to mobilize hematopoietic stem and progenitor cells (HSPC), but G-CSF is relatively inefficient and may cause adverse effects. Recently, adrenaline has been found to play important roles in HSPC mobilization. In this study, we explored whether adrenaline combined with G-CSF could induce HSPC mobilization in a mouse model. Mice were treated with adrenaline and either a high or low dose of G-CSF alone or in combination. Peripheral blood HSPC counts were evaluated by flow cytometry. Levels of bone marrow SDF-1 were measured by ELISA, the transcription of CXCR4 and SDF-1 was measured by real-time RT-PCR, and CXCR4 protein was detected by Western blot. Our results showed that adrenaline alone fails to mobilize HSPCs into the peripheral blood; however, when G-CSF and adrenaline are combined, the WBC counts and percentages of HSPCs are significantly higher compared to those in mice that received G-CSF alone. The combined use of adrenaline and G-CSF not only accelerated HSPC mobilization, but also enabled the efficient mobilization of HSPCs into the peripheral blood at lower doses of G-CSF. Adrenaline/G-CSF treatment also extensively downregulated levels of SDF-1 and CXCR4 in mouse bone marrow. These results demonstrated that adrenaline combined with G-CSF can induce HSPC mobilization by down-regulating the CXCR4/SDF-1 axis, indicating that the use of adrenaline may enable the use of reduced dosages or durations of G-CSF treatment, minimizing G-CSF-associated complications.

  17. Extension of Tissue Plasminogen Activator Treatment Window by Granulocyte-Colony Stimulating Factor in a Thromboembolic Rat Model of Stroke

    Directory of Open Access Journals (Sweden)

    Ike C. dela Peña

    2018-05-01

    Full Text Available When given beyond 4.5 h of stroke onset, tissue plasminogen activator (tPA induces deleterious side effects in the ischemic brain, notably, hemorrhagic transformation (HT. We examined the efficacy of granulocyte-colony stimulating factor (G-CSF in reducing delayed tPA-induced HT, cerebral infarction, and neurological deficits in a thromboembolic (TE stroke model, and whether the effects of G-CSF were sustained for longer periods of recovery. After stroke induction, rats were given intravenous saline (control, tPA (10 mg/kg, or G-CSF (300 μg/kg + tPA 6 h after stroke. We found that G-CSF reduced delayed tPA-associated HT by 47%, decreased infarct volumes by 33%, and improved motor and neurological deficits by 15% and 25%, respectively. It also prevented delayed tPA treatment-induced mortality by 46%. Immunohistochemistry showed 1.5- and 1.8-fold enrichment of the endothelial progenitor cell (EPC markers CD34+ and VEGFR2 in the ischemic cortex and striatum, respectively, and 1.7- and 2.8-fold increases in the expression of the vasculogenesis marker von Willebrand factor (vWF in the ischemic cortex and striatum, respectively, in G-CSF-treated rats compared with tPA-treated animals. Flow cytometry revealed increased mobilization of CD34+ cells in the peripheral blood of rats given G-CSF. These results corroborate the efficacy of G-CSF in enhancing the therapeutic time window of tPA for stroke treatment via EPC mobilization and enhancement of vasculogenesis.

  18. Occurrence of Leishmania infantum in the central nervous system of naturally infected dogs: Parasite load, viability, co-infections and histological alterations.

    Science.gov (United States)

    Oliveira, Valéria da Costa; Boechat, Viviane Cardoso; Mendes Junior, Artur Augusto Velho; Madeira, Maria de Fátima; Ferreira, Luiz Claudio; Figueiredo, Fabiano Borges; Campos, Monique Paiva; de Carvalho Rodrigues, Francisco das Chagas; Carvalhaes de Oliveira, Raquel de Vasconcellos; Amendoeira, Maria Regina Reis; Menezes, Rodrigo Caldas

    2017-01-01

    Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and little is known about the occurrence and pathogenesis of this parasite in the CNS. The aims of this study were to evaluate the occurrence, viability and load of L. infantum in the CNS, and to identify the neurological histological alterations associated with this protozoan and its co-infections in naturally infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum was isolated after necropsy were examined. Cerebrospinal fluid (CSF) samples were analyzed by parasitological culture, quantitative real-time PCR (qPCR) and the rapid immunochromatographic Dual Path Platform test. Brain, spinal cord and spleen samples were submitted to parasitological culture, qPCR, and histological techniques. Additionally, anti-Toxoplasma gondii and anti-Ehrlichia canis antibodies in serum and distemper virus antigens in CSF were investigated. None of the dogs showed neurological signs. All dogs tested positive for L. infantum in the CNS. Viable forms of L. infantum were isolated from CSF, brain and spinal cord in 25% of the dogs. Anti-L. infantum antibodies were detected in CSF in 61% of 36 dogs. Inflammatory histological alterations were observed in the CNS of 31% of the animals; of these, 66% were seropositive for E. canis and/or T. gondii. Amastigote forms were associated with granulomatous non-suppurative encephalomyelitis in a dog without evidence of co-infections. The highest frequency of L. infantum DNA was observed in the brain (98%), followed by the spinal cord (96%), spleen (95%), and CSF (50%). The highest L. infantum load in CNS was found in the spinal cord. These results demonstrate that L. infantum can cross the blood-brain barrier, spread through CSF, and cause active infection in the entire CNS of dogs. Additionally, L. infantum can cause inflammation in the CNS that can lead to neurological signs with progression of the disease.

  19. Occurrence of Leishmania infantum in the central nervous system of naturally infected dogs: Parasite load, viability, co-infections and histological alterations.

    Directory of Open Access Journals (Sweden)

    Valéria da Costa Oliveira

    Full Text Available Zoonotic visceral leishmaniasis is caused by the protozoan Leishmania infantum and little is known about the occurrence and pathogenesis of this parasite in the CNS. The aims of this study were to evaluate the occurrence, viability and load of L. infantum in the CNS, and to identify the neurological histological alterations associated with this protozoan and its co-infections in naturally infected dogs. Forty-eight Leishmania-seropositive dogs from which L. infantum was isolated after necropsy were examined. Cerebrospinal fluid (CSF samples were analyzed by parasitological culture, quantitative real-time PCR (qPCR and the rapid immunochromatographic Dual Path Platform test. Brain, spinal cord and spleen samples were submitted to parasitological culture, qPCR, and histological techniques. Additionally, anti-Toxoplasma gondii and anti-Ehrlichia canis antibodies in serum and distemper virus antigens in CSF were investigated. None of the dogs showed neurological signs. All dogs tested positive for L. infantum in the CNS. Viable forms of L. infantum were isolated from CSF, brain and spinal cord in 25% of the dogs. Anti-L. infantum antibodies were detected in CSF in 61% of 36 dogs. Inflammatory histological alterations were observed in the CNS of 31% of the animals; of these, 66% were seropositive for E. canis and/or T. gondii. Amastigote forms were associated with granulomatous non-suppurative encephalomyelitis in a dog without evidence of co-infections. The highest frequency of L. infantum DNA was observed in the brain (98%, followed by the spinal cord (96%, spleen (95%, and CSF (50%. The highest L. infantum load in CNS was found in the spinal cord. These results demonstrate that L. infantum can cross the blood-brain barrier, spread through CSF, and cause active infection in the entire CNS of dogs. Additionally, L. infantum can cause inflammation in the CNS that can lead to neurological signs with progression of the disease.

  20. Translocations (5;17) and (7;17) in patients with de novo or therapy-related myelodysplastic syndromes or acute nonlymphocytic leukemia. A possible association with acquired pseudo-Pelger-Hut anomaly and small vacuolated granulocytes

    International Nuclear Information System (INIS)

    La, J.L.Z.; Zandecki, M.; Fenaux, P.; Le Baron, F.; Bauters, F.; Cosson, A.; Deminatti, M.

    1990-01-01

    Twelve patients [two with de novo myelodysplastic syndrome (MDS), four with secondary MDS, five with de novo acute nonlymphocytic leukemia (ANLL), one with secondary ANLL] showed a 17p deletion resulting from translocations involving 17p: t(5;17)(p11;p11) in four cases, t(7;17)(p11;p11) in six cases, complex (5;17)(q23;p12) translocation with dicentric chromosome in one case, and t(17;?)(p11-12;?) in the remaining patient. All these structural anomalies were observed in hypodiploid clones associated with total or partial monosomy of chromosomes 5 and 7 (12 cases), monosomy 12 (five cases), monosomy 3 (four cases), and monosomy 4 (three cases). Median survival was only 3.3 months (range 3 days to 8 months). Striking features were observed in bone marrow mature granulocytes: all but one case had a pseudo-Pelger-Hut anomaly in a significant number of granulocytes, and eight patients had granulocytes with reduced size and clear cytoplasmic vacuoles. Careful cytological review of 51 patients with MDS or ANLL and various cytogenetic anomalies was performed for comparison: vacuolated granulocytes were a very uncommon finding. On the other hand, eight patients had a pseudo-Pelger-Hut anomaly, which correlated significantly with total monosomy 17 in these patients. A possible correlation between cytological anomalies and cytogenetic data is discussed, and the role of 17p in the nuclear segmentation of granulocytes is stressed

  1. Human prosthetic joint infections are associated with myeloid-derived suppressor cells (MDSCs): Implications for infection persistence.

    Science.gov (United States)

    Heim, Cortney E; Vidlak, Debbie; Odvody, Jessica; Hartman, Curtis W; Garvin, Kevin L; Kielian, Tammy

    2017-11-15

    Prosthetic joint infection (PJI) is a devastating complication of joint arthroplasty surgery typified by biofilm formation. Currently, mechanisms whereby biofilms persist and evade immune-mediated clearance in immune competent patients remain largely ill-defined. Therefore, the current study characterized leukocyte infiltrates and inflammatory mediator expression in tissues from patients with PJI compared to aseptic loosening. CD33 + HLA-DR - CD66b + CD14 -/low granulocytic myeloid-derived suppressor cells (G-MDSCs) were the predominant leukocyte population at sites of human PJI compared to aseptic tissues. MDSCs inhibit T cell proliferation, which coincided with reduced T cells in PJIs compared to aseptic tissues. IL-10, IL-6, and CXCL1 were significantly elevated in PJI tissues and have been implicated in MDSC inhibitory activity, expansion, and recruitment, respectively, which may account for their preferential increase in PJIs. This bias towards G-MDSC accumulation during human PJI could account for the chronicity of these infections by preventing the pro-inflammatory, antimicrobial actions of immune effector cells. Animal models of PJI have revealed a critical role for MDSCs and IL-10 in promoting infection persistence; however, whether this population is prevalent during human PJI and across distinct bacterial pathogens remains unknown. This study has identified that granulocytic-MDSC infiltrates are unique to human PJIs caused by distinct bacteria, which are not associated with aseptic loosening of prosthetic joints. Better defining the immune status of human PJIs could lead to novel immune-mediated approaches to facilitate PJI clearance in combination with conventional antibiotics. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

  2. Inductive potential of recombinant human granulocyte colony-stimulating factor to mature neutrophils from X-irradiated human peripheral blood hematopoietic progenitor cells

    International Nuclear Information System (INIS)

    Katsumori, Takeo; Yoshino, Hironori; Hayashi, Masako; Takahashi, Kenji; Kashiwakura, Ikuo

    2009-01-01

    Recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been used for treatment of neutropenia. Filgrastim, Nartograstim, and Lenograstim are clinically available in Japan. However, the differences in potential benefit for radiation-induced disorder between these types of rhG-CSFs remain unknown. Therefore, the effects of three different types of rhG-CSFs on granulocyte progenitor cells and expansion of neutrophils from nonirradiated or 2 Gy X-irradiated human CD34 + hematopoietic progenitor cells were examined. For analysis of granulocyte colony-forming units (CFU-G) and a surviving fraction of CFU-G, nonirradiated or X-irradiated CD34 + cells were cultured in methylcellulose containing rhG-CSF. These cells were cultured in serum-free medium supplemented with rhG-CSF, and the expansion and characteristics of neutrophils were analyzed. All three types of rhG-CSFs increased the number of CFU-G in a dose-dependent manner; however, Lenograstim is superior to others because of CFU-G-derived colony formation at relatively low doses. The surviving fraction of CFU-G was independent of the types of rhG-CSFs. Expansion of neutrophils by rhG-CSF was largely attenuated by X-irradiation, though no significant difference in neutrophil number was observed between the three types of rhG-CSFs under both nonirradiation and X-irradiation conditions. In terms of functional characteristics of neutrophils, Lenograstim-induced neutrophils produced high levels of reactive oxygen species compared to Filgrastim, when rhG-CSF was applied to nonirradiated CD34 + cells. In conclusion, different types of rhG-CSFs lead to different effects when rhG-CSF is applied to nonirradiated CD34 + cells, though Filgrastim, Nartograstim, and Lenograstim show equal effects on X-irradiated CD34 + cells. (author)

  3. Anti-human neutrophil antigen-1a, -1b, and -2 antibodies in neonates and children with immune neutropenias analyzed by extracted granulocyte antigen immunofluorescence assay.

    Science.gov (United States)

    Onodera, Rie; Kurita, Emi; Taniguchi, Kikuyo; Karakawa, Shuhei; Okada, Satoshi; Kihara, Hirotaka; Fujii, Teruhisa; Kobayashi, Masao

    2017-11-01

    Anti-human neutrophil antigen (HNA) antibodies have been implicated in the development of neonatal alloimmune neutropenia (NAN) and autoimmune neutropenia (AIN). There are many conventional assay methods that detect anti-HNA antibodies. However, a method to measure multiple samples and detect several anti-HNA antibodies simultaneously is needed. We developed a new method, the extracted granulocyte antigen immunofluorescence assay (EGIFA), to analyze anti-HNA-1a, -1b, and -2 antibodies in sera. The results obtained by EGIFA were evaluated in comparison with those from several standard assay methods. Anti-HNA antibodies in serum samples from nine familial cases with suspected NAN (n = 19) and children with suspected AIN (n = 88) were also measured by EGIFA. The evaluation of nine serum samples with anti-HNA antibodies suggested that EGIFA demonstrated equivalent specificity and superior sensitivity to monoclonal antibody-specific immobilization of granulocyte antigens and had comparable sensitivity to the granulocyte indirect immunofluorescence test. EGIFA successfully detected anti-HNA-1a or -1b antibodies in seven of nine familial cases with suspected NAN. EGIFA detected anti-HNA antibodies in 40.9% of children with suspected AIN. Among them, isolated anti-HNA-1a or -1b antibody was detected in 4.5 or 12.5% of children, respectively, and anti-HNA-2 antibody was identified in 3.4% of children. The 30.8% (16 of 52) of children negative for anti-HNA antibody by EGIFA were positive for anti-HLA antibody. EGIFA facilitated the measurement of anti-HNA-1a, -1b, and/or -2 antibodies in sera. The prompt measurement of anti-HNA antibodies will improve the diagnosis and clinical management of patients with suspected NAN or AIN. © 2017 AABB.

  4. The immunomodulatory effect of inhaled granulocyte-macrophage colony-stimulating factor in cystic fibrosis. A new treatment paradigm

    DEFF Research Database (Denmark)

    Heslet, Lars; Bay, Christiane; Nepper-Christensen, Steen

    2012-01-01

    Patients with cystic fibrosis (CF) experience recurrent infections and develop chronically infected lungs, which initiates an altered immunological alveolar environment. End-stage pulmonary dysfunction is a result of a long sequence of complex events in CF, progressing to alveolar macrophage dysf...

  5. Efficacy, safety and proper dose analysis of PEGylated granulocyte colony-stimulating factor as support for dose-dense adjuvant chemotherapy in node positive Chinese breast cancer patients

    OpenAIRE

    Zhang, Fan; LingHu, RuiXia; Zhan, XingYang; Li, Ruisheng; Feng, Fan; Gao, Xudong; Zhao, Lei; Yang, Junlan

    2017-01-01

    For high-risk breast cancer patients with positive axillary lymph nodes, dose-dense every-two-week epirubicin/cyclophosphamide-paclitaxel (ddEC-P) regimen is the optimal postoperative adjuvant therapy. However, this regimen is limited by the grade 3/4 neutropenia and febrile neutropenia (FN). There is an urgent need to explore the efficacy, safety and proper dosage of PEGylated granulocyte colony-stimulating factor (PEG-G-CSF) as support for ddEC-P in Chinese breast cancer patients with posit...

  6. Changes in adhesion molecule expression and oxidative burst activity of granulocytes and monocytes during open-heart surgery with cardiopulmonary bypass compared with abdominal surgery

    DEFF Research Database (Denmark)

    Toft, P; Nielsen, C H; Tønnesen, E

    1998-01-01

    surgery. The ability to respond with an oxidative burst was measured by means of flow cytometry using 123-dihydrorhodamine. The adhesion molecules CD11a/CD18, CD11c/CD18, CD44 were measured using monoclonal antibodies. Blood samples from eight patients undergoing open-heart surgery were taken before...... to an increased per-operative oxidative burst activity, and the induction of adhesion molecules on granulocytes associated with the cardiopulmonary bypass and surgery. In conclusion, open-heart surgery with cardiopulmonary bypass was associated with a rapid and pronounced activation of leukocytes which may play...

  7. Nuclear medicine imaging of bone infections

    International Nuclear Information System (INIS)

    Love, C.; Palestro, C.J.

    2016-01-01

    Osteomyelitis is a broad group of infectious diseases that involve the bone and/or bone marrow. It can arise haematogenously, via extension from a contiguous infection, or by direct inoculation during surgery or trauma. The diagnosis is not always obvious and imaging tests are frequently performed as part of the diagnostic work-up. Commonly performed radionuclide tests include technetium-99m ("9"9"mTc)-diphosphonate bone scintigraphy (bone), and gallium-67 ("6"7Ga) and in vitro labelled leukocyte (white blood cell; WBC) imaging. Although they are useful, each of these tests has limitations. Bone scintigraphy is sensitive but not specific, especially when underlying osseous abnormalities are present. "6"7Ga accumulates in tumour, trauma, and in aseptic inflammation; furthermore, there is typically an interval of 1–3 days between radiopharmaceutical injection of and imaging. Currently, this agent is used primarily for spinal infections. Except for the spine, WBC imaging is the nuclear medicine test of choice for diagnosing complicating osteomyelitis. The in vitro leukocyte labelling process requires skilled personnel, is laborious, and is not always available. Complementary marrow imaging is usually required to maximise accuracy. Not surprisingly, alternative radiopharmaceuticals are continuously being investigated. Radiolabelled anti-granulocyte antibodies and antibody fragments, investigated as in vivo leukocyte labelling agents, have their own limitations and are not widely available. "1"1"1In-biotin is useful for diagnosing spinal infections. Radiolabelled synthetic fragments of ubiquicidin, a naturally occurring human antimicrobial peptide that targets bacteria, have shown promise as infection specific radiopharmaceuticals. 2-["1"8F]-fluoro-2-deoxy-D-glucose (FDG) positron-emission tomography (PET) with or without computed tomography (CT) is very useful in musculoskeletal infection. Sensitivities of more than 95% and specificities ranging from 75–99% have

  8. The effect of Beauveria bassiana infection on cell mediated and humoral immune response in house fly, Musca domestica L.

    Science.gov (United States)

    Mishra, Sapna; Kumar, Peeyush; Malik, Anushree

    2015-10-01

    Entomopathogenic fungi that manifest infections by overcoming insect's immune response could be a successful control agent for the house fly, Musca domestica L. which is a major domestic, medical, and veterinary pest. In this study, the immune response of house fly to Beauveria bassiana infection was investigated to reveal fundamental aspects of house fly hemocyte biology, such as hemocyte numbers and size, which is poorly understood. The total hemocyte counts (THCs) in B. bassiana-infected house fly showed an initial increase (from 6 to 9 h), followed by subsequent decrease (9 to 12 h) with increase in time of infection. The THCs was slightly greater in infected flies than the non-infected ones. Insight into relative hemocyte counts depicted a significant increase in prohemocyte (PR) and decrease in granulocyte (GR) in infected house flies compared to non-infected ones. The relative cell area of hemocyte cells showed a noticeable increase in PR and intermediate cells (ICs), while a considerable reduction was observed for plasmatocyte (PL) and GR. The considerable variation in relative cell number and cell area in the B. bassiana-infected house flies indicated stress development during infection. The present study highlights changes occurring during B. bassiana invasion to house fly leading to establishment of infection along with facilitation in understanding of basic hemocyte biology. The results of the study is expected to help in better understanding of house fly immune response during fungal infection, so as to assist production of more efficient mycoinsecticides for house fly control using B. bassiana.

  9. 18F-F.D.G. PET imaging of infection and inflammation: intestinal, prosthesis replacements, fibrosis, sarcoidosis, tuberculosis.

    International Nuclear Information System (INIS)

    Fernandez, A.; Cortes, M.; Caresia, A.P.; Juan, R. de; Vidaller, A.; Mana, J.; Martinez-Yelamos, S.; Gamez, C.

    2008-01-01

    Nuclear medicine plays an important role in the evaluation of infection and inflammation. A variety of diagnostic methods are available for imaging this inflammation and infection, most notably computed tomography, 68 Ga scintigraphy or radionuclide labeled leucocytes. Fluorine 18 fluorodeoxyglucose ( 18 F-F.D.G.) is a readily available radiotracer that offers rapid, exquisitely sensitive high-resolution images by positron emission tomography (PET). Inflammation can be acute or chronic, the former showing predominantly neutrophilic granulocyte infiltrates, whereas in the latter, macrophages predominate. F.D.G. uptake in infection is based on the fact that mononuclear cells and granulocytes use large quantities of glucose by way of the hexose monophosphate shunts. 18 F-F.D.G. PET accurately helps diagnose spinal osteomyelitis, diabetic foot and in inflammatory conditions such as sarcoidosis and tuberculosis.(it appears to be useful for defining the extent of disease and monitoring response to treatment). 18 F-F.D.G. PET can also help localize the source of fever of undetermined origin, thereby guiding additional testing. 18 F-F.D.G. PET may be of limited usefulness in postoperative patients and in patients with a failed joint prosthesis or bowel inflammatory disease. In this review, we will focus on the role of 18 F-F.D.G. PET in the management of patients with inflammation or suspected or confirmed infection

  10. Granulocyte Colony-Stimulating Factor Use after Autologous Peripheral Blood Stem Cell Transplantation: Comparison of Two Practices.

    Science.gov (United States)

    Singh, Amrita D; Parmar, Sapna; Patel, Khilna; Shah, Shreya; Shore, Tsiporah; Gergis, Usama; Mayer, Sebastian; Phillips, Adrienne; Hsu, Jing-Mei; Niesvizky, Ruben; Mark, Tomer M; Pearse, Roger; Rossi, Adriana; van Besien, Koen

    2018-02-01

    Administration of granulocyte colony-stimulating factor (G-CSF) after autologous peripheral blood stem cell transplantation (PBSCT) is generally recommended to reduce the duration of severe neutropenia; however, data regarding the optimal timing of G-CSFs post-transplantation are limited and conflicting. This retrospective study was performed at NewYork-Presbyterian/Weill Cornell Medical Center between November 5, 2013, and August 9, 2016, of adult inpatient autologous PBSCT recipients who received G-CSF empirically starting on day +5 (early) versus on those who received G-CSF on day +12 only if absolute neutrophil count (ANC) was ANC-driven). G-CSF was dosed at 300 µg in patients weighing ANC-driven (n = 50) G-CSF regimen. Patient and transplantation characteristics were comparable in the 2 groups. In the ANC-driven group, 24% (n = 12) received G-CSF on day +12 and 60% (n = 30) started G-CSF earlier due to febrile neutropenia or at the physician's discretion, 6% (n = 3) started after day +12 at the physician's discretion, and 10% (n = 5) did not receive any G-CSF. The median start day of G-CSF therapy was day +10 in the ANC-driven group versus day +5 in the early group (P ANC-driven group (P = .07). There were no significant between-group differences in time to platelet engraftment, 1-year relapse rate, or 1-year overall survival. The incidence of febrile neutropenia was 74% in the early group versus 90% in the ANC-driven group (P = .04); however, there was no significant between-group difference in the incidence of positive bacterial cultures or transfer to the intensive care unit. The duration of G-CSF administration until neutrophil engraftment was 6 days in the early group versus 3 days in the ANC-driven group (P ANC-driven group (P = .28). Our data show that early initiation of G-CSF (on day +5) and ANC-driven initiation of G-CSF following autologous PBSCT were associated with a similar time to neutrophil engraftment

  11. Retinoic acid-induced granulocytic differentiation of HL60 human promyelocytic leukemia cells is preceded by downregulation of autonomous generation of inositol lipid-derived second messengers

    International Nuclear Information System (INIS)

    Porfiri, E.; Hoffbrand, A.V.; Wickremasinghe, R.G.

    1991-01-01

    Inositol phosphates (InsPs) and diacyglycerol (DAG) are second messengers derived via the breakdown of inositol phospholipids, and which play important signalling roles in the regulation of proliferation of some cell types. The authors have studied the operation of this pathway during the early stages of retionic acid (RA)-induced granulocytic differentiation of HL60 myeloid leukemia cells. The autonomous breakdown of inositol lipids that occurred in HL60 cells labeled with [3H] inositol was completely abolished following 48 hours of RA treatment. The rate of influx of 45Ca2+ was also significantly decreased at 48 hours, consistent with the role of inositol lipid-derived second messengers in regulating Ca2+ entry into cells. The downregulation of inositol lipid metabolism clearly preceded the onset of reduced proliferation induced by RA treatment, and was therefore not a consequence of decreased cell growth. The generation of InsPs in RA-treated cells was reactivated by the fluoroaluminate ion, a direct activator of guanine nucleotide-binding protein(s) (G proteins) that regulate the inositol lipid signalling pathway. Subtle alterations to a regulatory mechanism may therefore mediate the RA-induced downregulation of this pathway. The data are consistent with the hypothesis that the autonomous generation of inositol lipid-derived second messengers may contribute to the continuous proliferation of HL60 cells, and that the RA-induced downregulation of this pathway may, in turn, play a role in signalling the cessation of proliferation that preceedes granulocytic differentiation

  12. Influences of granulocyte growth factor in uterine perfusion on pregnancy outcome of patients with failure of embryo implantation for unknown reason.

    Science.gov (United States)

    He, Jun; Liu, Juan; Zhou, Hua; Chen, Chao Jun

    2016-11-01

    To investigate the influence of granulocyte growth factor in uterine perfusion on the pregnancy outcome of patients with failure of embryo implantation for unknown reason. Then, 68 patients with failure of embryo implantation for unknown reason were enrolled in our hospital from November 2013 to February 2015, which were divided into observation group and control group by random (34 patients in each group). Patients in observation group received basic treatment for granulocyte growth factor in uterine perfusion on the next day, while patients in control group received basic treatment with placebo. Then, endometrial preparation, adverse reaction and pregnancy outcome of patients were compared between the two groups. Comparing the endometrial preparation and average endometrial thickness of patients in control group (9.87±2.12) with those in observation group [(9.87±2.12), there is no significant difference (Pfactor, patients with failure of embryo implantation can effectively improve clinical pregnancy rate and embryo implantation rate without severe complication. Therefore, treatment of granlocyte growth factor can improve the pregnancy outcome of patients.

  13. A randomized case-controlled study of recombinant human granulocyte colony stimulating factor for the treatment of sepsis in preterm neutropenic infants.

    Science.gov (United States)

    Aktaş, Doğukan; Demirel, Bilge; Gürsoy, Tuğba; Ovalı, Fahri

    2015-06-01

    To investigate the efficacy and safety of recombinant human granulocyte colony-stimulating factor, recombinant human granulocyte-macrophage colony-stimulating factor (rhG-CSF) to treat sepsis in neutropenic preterm infants. Fifty-six neutropenic preterm infants with suspected or culture-proven sepsis hospitalized in Zeynep Kamil Maternity and Children's Educational and Training Hospital, Kozyatağı/Istanbul, Turkey between January 2008 and January 2010 were enrolled. Patients were randomized either to receive rhG-CSF plus empirical antibiotics (Group I) or empirical antibiotics alone (Group II). Clinical features were recorded. Daily complete blood count was performed until neutropenia subsided. Data were analyzed using SPSS version 11.5. Thirty-three infants received rhG-CSF plus antibiotic treatment and 23 infants received antibiotic treatment. No drug-related adverse event was recorded. Absolute neutrophil count values were significantly higher on the 2(nd) study day and 3(rd) study day in Group I. Short-term mortality did not differ between the groups. Treatment with rhG-CSF resulted in a more rapid recovery of ANC in neutropenic preterm infants. However, no reduction in short-term mortality was documented. Copyright © 2014. Published by Elsevier B.V.

  14. Enhanced granulocyte growth on peritoneal cell-coated membranes following irradiation: a dual effect of humoral stimulation and repair of x ray-induced damage to the microenvironment

    International Nuclear Information System (INIS)

    Turner, A.R.; Pfrimmer, W.J.; Boggs, D.R.; Carpe, A.I.

    1978-01-01

    An experimental model of the hematopoietic microenvironment was created by allowing a peritoneal cell coating to form on a disk of cellulose acetate placed in the peritoneal cavity of mice. An effective microenvironment capable of supporting colony growth, primarily granulocytic, was established if the cellulose acetate disk was in the peritoneum for 3 to 5 days. Its effectiveness was hampered by transferring it to another mouse or by exposure to toxic agents such as a propylene glycol-ethanol mixture or irradiation. An exponential dose-related decrease in colony formation was seen with increasing doses or irradiation of the microenvironment before colonization. After a low dose of irradiation, recovery of colony support capacity occurred over a 6-day period. Enhancement of colony growth was seen when cell injection was delayed for 2 to 3 days after irradiation. The effects of irradiation on the cellular stroma were separated from the systemic changes in the host by transferring an established hematopoietic microenvironment to a secondary host. It was shown that there are two distinct effects of irradiation on granulocytic colony growth; one was a short-lived period, 2 to 3 days of stimulation, presumably humoral, and the other was dose-dependent reversible microenvironment damage

  15. Retrospective study of clinical and hematological aspects associated with dogs naturally infected by Hepatozoon canis in Ludhiana, Punjab, India

    Science.gov (United States)

    Chhabra, Sushma; Uppal, Sanjeev Kumar; Singla, Lachhman Das

    2013-01-01

    Objective To evaluate clinical and hematological aspects of dogs naturally infected with Hepatozoon canis (H. canis) presented at the Small Animal Clinics of Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana. Methods Blood films of 34 naturally infected dogs were examined for haematological alterations and parasitaemia. Signalment and clinical signs were recorded from the animals. Clinical histories were filled out during the consultation. Results Of the 34 positive dogs by Giemsa stained peripheral blood films, 88.23% presented parasitaemia by H. canis only, while 11.77% had the combination of H. canis, Babesia sp. and Ehrlichia sp. Young male dogs less than one-year-old, of non-descript breed, were the most commonly affected. And 26.47% were presented with anorexia/inappetence as the only clinical symptom. Other clinical symptoms were mild to moderate fever, pale mucosae and lethargy; a few were also showing the signs of vomiting and diarrhoea. Haematological alterations showed mainly normochromic-normocytic anaemia, leukocytosis and neutrophilia. Conclusions The findings of this study substantiate that H. canis caused clinical and haematological alterations of the varied intensity in dogs, even with low parasitaemia, should be taken into consideration. PMID:23730562

  16. Retrospective study of clinical and hematological aspects associated with dogs naturally infected by Hepatozoon canis in Ludhiana, Punjab, India.

    Science.gov (United States)

    Chhabra, Sushma; Uppal, Sanjeev Kumar; Singla, Lachhman Das

    2013-06-01

    To evaluate clinical and hematological aspects of dogs naturally infected with Hepatozoon canis (H. canis) presented at the Small Animal Clinics of Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana. Blood films of 34 naturally infected dogs were examined for haematological alterations and parasitaemia. Signalment and clinical signs were recorded from the animals. Clinical histories were filled out during the consultation. Of the 34 positive dogs by Giemsa stained peripheral blood films, 88.23% presented parasitaemia by H. canis only, while 11.77% had the combination of H. canis, Babesia sp. and Ehrlichia sp. Young male dogs less than one-year-old, of non-descript breed, were the most commonly affected. And 26.47% were presented with anorexia/inappetence as the only clinical symptom. Other clinical symptoms were mild to moderate fever, pale mucosae and lethargy; a few were also showing the signs of vomiting and diarrhoea. Haematological alterations showed mainly normochromic-normocytic anaemia, leukocytosis and neutrophilia. The findings of this study substantiate that H. canis caused clinical and haematological alterations of the varied intensity in dogs, even with low parasitaemia, should be taken into consideration.

  17. Ixodid ticks and tick-borne infections in the republic of Cuba – literature review and rationale for risk assessment

    Directory of Open Access Journals (Sweden)

    Khasnatinov M.A.

    2018-04-01

    Full Text Available The Republic of Cuba is a popular destination for Russian tourists and about 30-50 thousands of Russian citizens visit Cuba annually. However, the recreational activity is often associated with the risk of Ixodid ticks bites and infection with tick-borne pathogens. According to published literature, the fauna of the hard tick in Cuba is represented by nine species including Ixodes capromydis, Amblyomma albopictum, A. cajennense, A. dissimile, A. quadricavum, A. torrei, Dermacentor nitens, Rhipicephalus sanguineus and R. (Boophilus microplus. Five of these species, i.e. A. cajennense, A. dissimile, D. nitens, R. sanguineus and R. (Boophilus microplus, were reported as human parasites. Ticks are spread over the most part of the island territory. Several tick-borne pathogens should be considered as a potential threat for the bitten humans in Cuba, including Borrelia burgdorferi sensu lato, Rickettsia sp., Anaplasma sp., Ehrlichia sp., Coxiella sp., thogotovirus and Crimean-Congo hemorrhagic fever virus. Implications for the epidemiology of tick-borne infections in the Russian Federation are discussed.

  18. Apresentação incomum de sarcoma granulocítico mamário Unusual presentation of granulocytic sarcoma in the breasts

    Directory of Open Access Journals (Sweden)

    Francisco D. Rocha Filho

    2009-08-01

    Full Text Available O termo sarcoma granulocítico (SG designa um raro tumor sólido composto de agregados de precursores granulocíticos imaturos em sítios extramedulares. A lesão geralmente ocorre durante o curso natural da leucemia mieloide aguda (LMA ou após sua remissão. O SG primário manifesta-se mais comumente na pele e linfonodos, portanto, quando se apresenta na mama, o erro diagnóstico de linfoma não Hodgkin, carcinoma lobular, sarcoma e melanoma maligno é um problema comum. A mama tem sido relatada como um local incomum de SG. Relata-se um caso raro de SG bilateral em mamas concomitante com LMA numa mulher de 47 anos. A paciente foi admitida em nosso hospital devido a manifestações neurológicas e descobrimos, durante a investigação, tumorações nas mamas. A histopatologia das lesões sugeriu linfoma não Hodgkin, sendo iniciada quimioterapia esquema CHOP. No entanto, o mielograma mostrou hiperplasia das séries granulocíticas, e a imuno-histoquímica revelou mieloperoxidase e CD68 positivos, confirmando o diagnóstico de SG primário em mamas. A citogenética não detectou anomalias. A revisão da microscopia e a análise do líquor confirmaram a presença de infiltração no parênquima mamário e no sistema nervoso central por leucemia monoblástica aguda (LMA-M5a. O protocolo de indução da remissão foi iniciado com daunorrubicina, arabinosídeo-C e quimioterapia intratecal com metotrexate, arabinosídeo-C e dexametasona (MADIT. Um mês depois, a paciente recusou a continuação do tratamento, depois de ter feito pedido de alta.Granulocytic sarcoma (GS is an uncommon solid tumor composed of aggregates of immature granulocytic precursors in extramedullary sites. The lesion generally occurs during the natural course of acute myelogenous leukemia or after remission has been achieved. Primary GS manifests most commonly in skin and lymph nodes, therefore when it presents in the breast, misdiagnosis of non-Hodgkin's lymphoma, lobular

  19. Rotavirus infection

    Science.gov (United States)

    Crawford, Sue E.; Ramani, Sasirekha; Tate, Jacqueline E.; Parashar, Umesh D.; Svensson, Lennart; Hagbom, Marie; Franco, Manuel A.; Greenberg, Harry B.; O’Ryan, Miguel; Kang, Gagandeep; Desselberger, Ulrich; Estes, Mary K.

    2017-01-01

    Rotavirus infections are a leading cause of severe, dehydrating gastroenteritis in children rotavirus over a decade ago, rotavirus infections still result in >200,000 deaths annually, mostly in low-income countries. Rotavirus primarily infects enterocytes and induces diarrhoea through the destruction of absorptive enterocytes (leading to malabsorption), intestinal secretion stimulated by rotavirus non-structural protein 4 and activation of the enteric nervous system. In addition, rotavirus infections can lead to antigenaemia (which is associated with more severe manifestations of acute gastroenteritis) and viraemia, and rotavirus can replicate in systemic sites, although this is limited. Reinfections with rotavirus are common throughout life, although the disease severity is reduced with repeat infections. The immune correlates of protection against rotavirus reinfection and recovery from infection are poorly understood, although rotavirus-specific immunoglobulin A has a role in both aspects. The management of rotavirus infection focuses on the prevention and treatment of dehydration, although the use of antiviral and anti-emetic drugs can be indicated in some cases. PMID:29119972

  20. Augmented effect of early antibiotic treatment in mice with experimental lung infections due to sequentially adapted mucoid strains of Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    van Gennip, M; Moser, Claus; Christensen, Louise D

    2009-01-01

    : A significant reduction in the number of bacteria was observed when initiating treatment 1 h post-infection compared with initiating treatment after 24 h, although the latest isolate avoided complete clearance. Early antibiotic treatment directed at the mucoid phenotype in mice also reduced the inflammation and......Background: Effects of treatment with tobramycin initiated 1 or 24 h post-infection were investigated in a new version of a pulmonary infection model in mice. The model reflects the differentiated behaviour of Pseudomonas aeruginosa mucoid strains isolated from the lungs of one chronically infected......, histopathology, and measurement of granulocyte colony-stimulating factor (G-CSF) and macrophage inflammatory protein 2 (MIP-2). Results: There was a significant reduction of bacteria when comparing treatment initiated 1 h post-infection with treatment initiated after 24 h for isolates 1997 and 2003. Treatment...

  1. Effect of granulocyte colony-stimulating factor on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation

    International Nuclear Information System (INIS)

    Zhao Hongxia; Guo Mei; Sun Xuedong; Ai Huisheng

    2011-01-01

    Objective: To investigate the effects of recombinant human granulocyte colony stimulating factor (G-CSF) on murine thymic emigration and subsets reconstitution after a sublethal dose of irradiation. Methods: Female BALB/c mice were irradiated with a 6.0 Gy of γ-ray total-body irradiation and then randomly divided into GCSF group and control group. For mice in the GCSF group, recombinant human G-CSF 100 μg · kg -1 · d -1 was injected subcutaneously once daily for 14 continuous days and mice in the control group were given the same volume of phosphate buffered solution (PBS). At 7, 14, 21 and 28 days later, mice were killed and thymus mononuclear cell suspension were analyzed by flow cytometry for the percentage of the four stages of thymic CD4 - CD8 - double negative cells (DN1-4) and the CD4 + CD8 + double positive ( CD4 + CD8 + DP), CD4 + CD8 - single positive (CD4 + SP), CD4 - CD8 + single positive cells (CD8 + SP).Real-time PCR was used for detection and quantitation of murine T cell receptor rearrangement excision circles (sjTRECs) of the thymic cells of 30 and 60 d after irradiation. Results: The percentage of thymic DN1 cells in GCSF group was significantly higher than that of the control group 7 d after irradiation (t=9.59, P<0.05). 21 d later, the proportion of thymic DN3 and DN4 cells were higher than those of the control group (t=16.37, 7.6, P<0.05). The percentage of thymic CD4 + CD8 + DP cells decreased 7 d after irradiation,increased at 14 d, decreased again at 21 days,and then got a permanent recover. The percentage of thymic CD4 + CD8 + DP cells in the GCSF group recovered to normal and was significantly higher than that of the control group 28 days after irradiation (t=12.22, P<0.05). The percentage of thymic CD8 + SP cells of the GCSF group was significantly higher than that of the control group 21 d after irradiation (t=3.77, P<0.05), while G-CSF had no obvious influence on the percentage of the thymic CD4 + SP cells. The sjTRECs copies in the

  2. Increased Frequency of Peripheral B and T Cells Expressing Granulocyte Monocyte Colony-Stimulating Factor in Rheumatoid Arthritis Patients

    Directory of Open Access Journals (Sweden)

    Anastasia Makris

    2018-01-01

    Full Text Available ObjectivesGranulocyte monocyte colony-stimulating factor (GM-CSF is currently considered a crucial inflammatory mediator and a novel therapeutic target in rheumatoid arthritis (RA, despite the fact that its precise cellular sources remain uncertain. We studied the expression of GM-CSF in peripheral lymphocytes from RA patients and its change with antirheumatic therapies.MethodsIntracellular GM-CSF expression was assessed by flow cytometry in stimulated peripheral B (CD19+ and T (CD3+ cells from RA patients (n = 40, disease (n = 31 including osteoarthritis n = 15, psoriatic arthritis n = 10, and systemic rheumatic diseases n = 6 and healthy (n = 16 controls. The phenotype of GM-CSF+ B cells was assessed as well as longitudinal changes in GM-CSF+ lymphocytes during methotrexate (MTX, n = 10 or anti-tumor necrosis factor (anti-TNF, n = 10 therapy.ResultsAmong untreated RA patients with active disease (Disease Activity Score 28-C-reactive protein = 5.6 ± 0.89 an expanded population of peripheral GM-CSF+ B (4.1 ± 2.2% and T (3.4 ± 1.6% cells was detected compared with both disease (1.7 ± 0.9%, p < 0.0001 and 1.7 ± 1.3%, p < 0.0001, respectively and healthy (0.3 ± 0.2%, p < 0.0001 and 0.6 ± 0.6%, p < 0.0001 controls. RA GM-CSF+ B cells displayed more commonly a plasmablast or transitional phenotype (37.12 ± 18.34% vs. 14.26 ± 9.46%, p = 0.001 and 30.49 ± 15.04% vs. 2.45 ± 1.84%, p < 0.0001, respectively and less a memory phenotype (21.46 ± 20.71% vs. 66.99 ± 16.63%, p < 0.0001 compared to GM-CSF− cells. GM-CSF expression in RA patients did not correlate to disease duration, activity or serological status. Anti-TNF treatment led to a statistically significant decrease in GM-CSF+ B and T cells while MTX had no significant effect.DiscussionThis is the first study showing an expanded population of GM-CSF+ B and T lymphocytes

  3. Hookworm infection

    Science.gov (United States)

    ... intestinal wall and suck blood, which results in iron deficiency anemia and protein loss. Adult worms and larvae are ... problems that may result from hookworm infection include: Iron deficiency anemia , caused by loss of blood Nutritional deficiencies Severe ...

  4. Breast infection

    Science.gov (United States)

    Mastitis; Infection - breast tissue; Breast abscess ... must continue to breastfeed or pump to relieve breast swelling from milk production. In case if the abscess does not go away, needle aspiration under ultrasound ...

  5. Biofilm Infections

    DEFF Research Database (Denmark)

    Bjarnsholt, Thomas; Jensen, Peter Østrup; Moser, Claus Ernst

    A still increasing interest and emphasis on the sessile bacterial lifestyle biofilms has been seen since it was realized that the vast majority of the total microbial biomass exists as biofilms. Aggregation of bacteria was first described by Leeuwenhoek in 1677, but only recently recognized...... as being important in chronic infection. In 1993 the American Society for Microbiology (ASM) recognized that the biofilm mode of growth was relevant to microbiology. This book covers both the evidence for biofilms in many chronic bacterial infections as well as the problems facing these infections...... such as diagnostics, pathogenesis, treatment regimes and in vitro and in vivo models for studying biofilms. This is the first scientific book on biofilm infections, chapters written by the world leading scientist and clinicians. The intended audience of this book is scientists, teachers at university level as well...

  6. Spinal Infections

    Science.gov (United States)

    ... the wound and re-closing to more extensive debridements and removal of infected tissues. In some cases ... will want to obtain cultures to determine the type of bacteria or fungus that is causing the ...

  7. Neonatal Infections

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    ... can cause serious problems such as heart disease, brain damage, deafness, visual impairment, or even miscarriage. Infection later in the pregnancy may lead to less severe effects on the fetus but can still cause problems ...

  8. Anaerobic Infections

    Science.gov (United States)

    ... a dental infection or procedure such as a tooth extraction or oral surgery or after trauma to the ... diagnosed, your doctor may treat it with intravenous antibiotics (