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Sample records for mannheimia haemolytica a1

  1. Mannheimia haemolytica A1-induced fibrinosuppurative meningoencephalitis in a naturally-infected Holstein-Friesian calf

    USDA-ARS?s Scientific Manuscript database

    Mannheimia haemolytica is an opportunistic bacterium that is widely recognized among the bovine respiratory disease complex as the predominant pathogen associated with pleuropneumonia in cattle. Among the characterized M. haemolytica serotypes, A1 is the major cause of severe pulmonary lesions in ca...

  2. Mannheimia haemolytica A1-induced fibrinosuppurative meningoencephalitis in a naturally-infected Holstein-Friesian calf.

    PubMed

    Aschenbroich, S; Nemeth, N; Rech, R; Briggs, R; Sanchez, S; Brown, C

    2013-01-01

    Mannheimia haemolytica is an opportunistic bacterium that is widely recognized among the bovine respiratory disease complex as the predominant pathogen causing broncho- and pleuropneumonia in cattle. Among the characterized M. haemolytica serotypes, A1 is the major cause of severe pulmonary lesions in cattle. This report describes post-mortem findings in a Holstein-Friesian calf with fibrinosuppurative meningoencephalitis and fibrinonecrotizing, haemorrhagic broncho- and pleuropneumonia, from which M. haemolytica and bovine viral diarrhoea virus (BVDV) were isolated. Microscopical evaluation showed expansion of the brainstem and cerebellar leptomeninges by neutrophils and fibrin, associated with gram-negative coccobacilli. Occasional blood vessels within the midbrain and cerebellum contained fibrin thrombi. Bacterial culture of cerebellum and lung yielded M. haemolytica with unusually high haemolytic activity. The isolates were confirmed as serotype A1 by rapid plate agglutination. Lung tissue was positive for BVDV by polymerase chain reaction. The broncho- and pleuropneumonia in this calf were consistent with typical mannheimiosis due to serotype A1; however, extrapulmonary infections due to M. haemolytica, as seen in this case, are rarely reported. To our knowledge, this is the first documentation of a natural BVDV and M. haemolytica co-infection associated with fibrinosuppurative meningoencephalitis in a calf. Copyright © 2013 Elsevier Ltd. All rights reserved.

  3. Genome sequences of Mannheimia haemolytica serotype A1 strains D153 and D193 from bovine pneumonia

    USDA-ARS?s Scientific Manuscript database

    Here we report two genomes, one complete and one draft, from virulent bovine strains of Mannheimia haemolytica(strains D171 and D35)serotype A2 recovered prior to the field usage of modern antimicrobial drugs....

  4. Mannheimia haemolytica serotype A1 exhibits differential pathogenicity in two related species, Ovis canadensis and Ovis aries.

    PubMed

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Herndon, Caroline N; Lawrence, Paulraj K; Frances Cassirer, E; Potter, Kathleen A; Foreyt, William J; Clinkenbeard, Kenneth D; Srikumaran, Subramaniam

    2009-02-02

    Mannheimia haemolytica causes pneumonia in both bighorn sheep (BHS, Ovis canadensis) and domestic sheep (DS, Ovis aries). Under experimental conditions, co-pasturing of BHS and DS results in fatal pneumonia in BHS. It is conceivable that certain serotypes of M. haemolytica carried by DS are non-pathogenic to them, but lethal for BHS. M. haemolytica serotypes A1 and A2 are carried by DS in the nasopharynx. However, it is the serotype A2 that predominantly causes pneumonia in DS. The objectives of this study were to determine whether serotype A1 exhibits differential pathogenicity to BHS and DS, and to determine whether leukotoxin (Lkt) secreted by this organism is its primary virulence factor. Three groups each of BHS and DS were intra-tracheally administered either 1 x 10(9)cfu of serotype A1 wild-type (lktA-Wt group), Lkt-deletion mutant of serotype A1-(lktA-Mt group), or saline (control group), respectively. In the lktA-Wt groups, all four BHS died within 48h while none of the DS died during the 2-week study period. In the lktA-Mt groups, none of the BHS or DS died. In the control groups, one DS died due to an unrelated cause. Necropsy and histopathological findings revealed that death of BHS in the lktA-Wt group was due to bilateral, fibrinohemorrhagic pneumonia. Although the A1-Mt-inoculated BHS were clinically normal, on necropsy, lungs of two BHS showed varying degrees of mild chronic pneumonia. These results indicate that M. haemolytica serotype A1 is non-pathogenic to DS, but highly lethal to BHS, and that Lkt is the primary virulence factor of M. haemolytica.

  5. Complete closed genome sequences of a Mannheimia haemolytica serotype A1 leukotoxin deletion mutant and its wild type parent strain

    USDA-ARS?s Scientific Manuscript database

    Mannheimia haemolytica is a bacterial pathogen associated with bovine respiratory disease complex (BRDC). It secretes a leukotoxin that binds to CD18 on leukocyte membranes and causes acute inflammation and lung injury characteristic of BRDC. We report the complete closed genome sequences of a leu...

  6. Complete closed genome sequences of Mannheimia haemolytica serotypes A1 and A6 isolated from cattle

    USDA-ARS?s Scientific Manuscript database

    Mannhemimia haemolytica is a respiratory pathogen affecting cattle and related ruminants worldwide. M. haemolytica is commonly associated with Bovine Respiratory Disease Complex (BRDC), a polymicrobial, multifactorial disease. We present the first two complete closed genomes of this species using a...

  7. Genome Sequence of a Presumptive Mannheimia haemolytica Strain with an A1/A6-Cross-Reactive Serotype from a White-Tailed Deer (Odocoileus virginianus).

    PubMed

    Lawrence, Paulraj K; Bey, Russell F; Wiener, Brittanny; Kittichotirat, Weerayuth; Bumgarner, Roger E

    2014-03-27

    Mannheimia haemolytica is a Gram-negative bacterium and the principal etiological agent associated mostly with bovine respiratory disease complex. However, we report here the sequence of a strain with the novel A1/A6-cross-reactive serotype, strain PKL10, isolated from white-tailed deer. PKL10 was isolated from the spleen of farmed white-tailed deer showing clinical signs of pneumonia. The genome structure of PKL10 is dramatically different from that of previously sequenced isolates, which was demonstrated by genome alignments. In addition, the coding sequences in PKL10 share approximately 86% sequence identity with the coding sequences in other fully sequenced M. haemolytica strains. This suggests that PKL10 is a novel Mannheimia species.

  8. Mannheimia haemolytica vegetative endocarditis in a Suffolk wether

    PubMed Central

    LaHue, Nathaniel; Parish, Steven

    2015-01-01

    A 12-week-old Suffolk wether was diagnosed with bacterial endocarditis associated with Mannheimia haemolytica. The wether had shown signs of lethargy, inappetance, fever, and a grade 5 of 6 holosystolic murmur. Mannheimia haemolytica was cultured from blood premortem and the valvular lesion postmortem. PMID:25969581

  9. A Multivalent Mannheimia-Bibersteinia Vaccine Protects Bighorn Sheep against Mannheimia haemolytica Challenge ▿

    PubMed Central

    Subramaniam, Renuka; Shanthalingam, Sudarvili; Bavananthasivam, Jegarubee; Kugadas, Abirami; Potter, Kathleen A.; Foreyt, William J.; Hodgins, Douglas C.; Shewen, Patricia E.; Barrington, George M.; Knowles, Donald P.; Srikumaran, Subramaniam

    2011-01-01

    Bighorn sheep (BHS) are more susceptible than domestic sheep (DS) to Mannheimia haemolytica pneumonia. Although both species carry M. haemolytica as a commensal bacterium in the nasopharynx, DS carry mostly leukotoxin (Lkt)-positive strains while BHS carry Lkt-negative strains. Consequently, antibodies to surface antigens and Lkt are present at much higher titers in DS than in BHS. The objective of this study was to determine whether repeated immunization of BHS with multivalent Mannheimia-Bibersteinia vaccine will protect them upon M. haemolytica challenge. Four BHS were vaccinated with a culture supernatant vaccine prepared from M. haemolytica serotypes A1 and A2 and Bibersteinia trehalosi serotype T10 on days 0, 21, 35, 49, and 77. Four other BHS were used as nonvaccinated controls. On the day of challenge, 12 days after the last immunization, the mean serum titers of Lkt-neutralizing antibodies and antibodies to surface antigens against M. haemolytica were 1:160 and 1:4,000, respectively. Following intranasal challenge with M. haemolytica A2 (1 × 105 CFU), all four control BHS died within 48 h. Necropsy revealed acute fibrinonecrotic pneumonia characteristic of M. haemolytica infection. None of the vaccinated BHS died during the 8 weeks postchallenge observation period. Radiography at 3 weeks postchallenge revealed no lung lesions in two vaccinated BHS and mild lesions in the other two, which resolved by 8 weeks postchallenge. These results indicate that if BHS can be induced to develop high titers of Lkt-neutralizing antibodies and antibodies to surface antigens, they are likely to survive M. haemolytica challenge which is likely to reduce the BHS population decline due to pneumonia. PMID:21832104

  10. A multivalent Mannheimia-Bibersteinia vaccine protects bighorn sheep against Mannheimia haemolytica challenge.

    PubMed

    Subramaniam, Renuka; Shanthalingam, Sudarvili; Bavananthasivam, Jegarubee; Kugadas, Abirami; Potter, Kathleen A; Foreyt, William J; Hodgins, Douglas C; Shewen, Patricia E; Barrington, George M; Knowles, Donald P; Srikumaran, Subramaniam

    2011-10-01

    Bighorn sheep (BHS) are more susceptible than domestic sheep (DS) to Mannheimia haemolytica pneumonia. Although both species carry M. haemolytica as a commensal bacterium in the nasopharynx, DS carry mostly leukotoxin (Lkt)-positive strains while BHS carry Lkt-negative strains. Consequently, antibodies to surface antigens and Lkt are present at much higher titers in DS than in BHS. The objective of this study was to determine whether repeated immunization of BHS with multivalent Mannheimia-Bibersteinia vaccine will protect them upon M. haemolytica challenge. Four BHS were vaccinated with a culture supernatant vaccine prepared from M. haemolytica serotypes A1 and A2 and Bibersteinia trehalosi serotype T10 on days 0, 21, 35, 49, and 77. Four other BHS were used as nonvaccinated controls. On the day of challenge, 12 days after the last immunization, the mean serum titers of Lkt-neutralizing antibodies and antibodies to surface antigens against M. haemolytica were 1:160 and 1:4,000, respectively. Following intranasal challenge with M. haemolytica A2 (1 × 10(5) CFU), all four control BHS died within 48 h. Necropsy revealed acute fibrinonecrotic pneumonia characteristic of M. haemolytica infection. None of the vaccinated BHS died during the 8 weeks postchallenge observation period. Radiography at 3 weeks postchallenge revealed no lung lesions in two vaccinated BHS and mild lesions in the other two, which resolved by 8 weeks postchallenge. These results indicate that if BHS can be induced to develop high titers of Lkt-neutralizing antibodies and antibodies to surface antigens, they are likely to survive M. haemolytica challenge which is likely to reduce the BHS population decline due to pneumonia.

  11. Genome Sequence of Mannheimia haemolytica Serotype 1 Strain 16041065 BH

    PubMed Central

    Ayalew, Sahlu; Confer, Anthony W.; Hansen, Richard D.

    2017-01-01

    ABSTRACT Here, we report the genome sequence of Mannheimia haemolytica serotype 1 strain 16041065 BH, which was recently isolated from a Midwestern calf that died due to Mannheimia haemolytica–induced pneumonia. This genome comprised a total of 2.7 Mb, with an N50 of 122 kb, and maintained hemolytic activity when grown on blood heart infusion agar supplemented with 5% sheep’s blood. PMID:28385859

  12. Mannheimia haemolytica and Bibersteinia trehalosi Serotypes Isolated from Merino Breed Lambs in Extremadura (Southwestern Spain).

    PubMed

    Fernández, Sara; Galapero, Javier; Gómez, Luis; Pérez, Carlos J; Cid, Dolores; Martín, M Carmen; Alonso, Juan Manuel; Rey, Joaquín

    2016-12-01

    Pneumonia caused by Mannheimia haemolytica is an important disease in ruminants. Because of its economic significance, several methods have been developed to study the pathogenicity and epidemiology of M. haemolytica. In this study, bacterial isolates of M. haemolytica and Bibersteinia trehalosi identified from the lungs of sheep were serotyped by means of indirect haemagglutination. Of the 598 lungs studied, 34 isolates were identified and serotyped. In decreasing order, M. haemolytica serotypes were: not typable (50 %), A1 (17.65 %), A7 (11.76 %), A6 (5.88 %), and A12, A2, A5 and A9 (each representing 2.94 %). The only B. trehalosi serotype was T4 (2.94 %). Serotypes A1, A6 and A7 of M. haemolytica were the most commonly isolated from pneumonic sheep producing greater changes in the lungs and having important implications for sheep production.

  13. Immunogenicity of Pasteurella multocida and Mannheimia haemolytica outer membrane vesicles

    PubMed Central

    Roier, Sandro; Fenninger, Judith C.; Leitner, Deborah R.; Rechberger, Gerald N.; Reidl, Joachim; Schild, Stefan

    2013-01-01

    Pasteurella multocida is able to cause disease in humans and in a wide range of animal hosts, including fowl cholera in birds, atrophic rhinitis in pigs, and snuffles in rabbits. Together with Mannheimia haemolytica, P. multocida also represents a major bacterial causative agent of bovine respiratory disease (BRD), which is one of the most important causes for economic losses for the cattle backgrounding and feedlot industry. Commercially available vaccines only partially prevent infections caused by P. multocida and M. haemolytica. Thus, this study characterized the immunogenicity of P. multocida and M. haemolytica outer membrane vesicles (OMVs) upon intranasal immunization of BALB/c mice. Enzyme-linked immunosorbent assays (ELISA) revealed that OMVs derived from P. multocida or M. haemolytica are able to induce robust humoral and mucosal immune responses against the respective donor strain. In addition, also significant cross-immunogenic potential was observed for both OMV types. Colonization studies showed that a potential protective immune response against P. multocida is not only achieved by immunization with P. multocida OMVs, but also by immunization with OMVs derived from M. haemolytica. Immunoblot and immunoprecipitation analyses demonstrated that M. haemolytica OMVs induce a more complex immune response compared to P. multocida OMVs. The outer membrane proteins OmpA, OmpH, and P6 were identified as the three major immunogenic proteins of P. multocida OMVs. Amongst others, the serotype 1-specific antigen, an uncharacterized outer membrane protein, as well as the outer membrane proteins P2 and OmpA were found to be the most important antigens of M. haemolytica OMVs. These findings are useful for the future development of broad-spectrum OMV based vaccines against BRD and other infections caused by P. multocida or M. haemolytica. PMID:23731905

  14. Characterization of Mannheimia haemolytica biofilm formation in vitro.

    PubMed

    Boukahil, Ismail; Czuprynski, Charles J

    2015-01-30

    Mannheimia haemolytica is the primary bacterial agent in the bovine respiratory disease complex. It is thought that M. haemolytica colonizes the tonsillar crypts of cattle as a commensal and subsequently descends into the lungs to cause disease. Many bacterial species persist in the host as biofilms. There is limited information about the ability of M. haemolytica to form biofilms. The aim of this study was to develop an in vitro model for M. haemolytica biofilm formation. We found that M. haemolytica required at least 36 h to form robust biofilms on plastic in vitro when incubated in RPMI-1640 tissue culture medium at 37 °C, with maximal biofilm formation being evident at 48 h. Biofilm formation was inhibited by adding the monosaccharides d(+) galactose and d(+) mannose to the growth medium. Addition of antibodies to the M. haemolytica surface protein OmpA also reduced biofilm formation. Upon evaluating the macromolecules within the biofilm extracellular polymeric substance we found it contained 9.7 μg/cm(2) of protein, 0.81 μg/cm(2) of total carbohydrate, and 0.47 μg/cm(2) of extracellular DNA. Furthermore, proteinase K treatment significantly decreased biofilms (P<0.05) while α-amylase and micrococcal nuclease decreased biofilms to a lesser extent. M. haemolytica biofilm cells were more resistant than planktonic cells to the antibiotics florfenicol, gentamicin, and tulathromycin. These results provide evidence that M. haemolytica can form biofilms, which could contribute to its ability to persist as a commensal in the bovine upper respiratory tract.

  15. Bibersteinia trehalosi inhibits the growth of mannheimia haemolytica by a proximity-dependent mechanism

    USDA-ARS?s Scientific Manuscript database

    Mannheimia (Pasteurella) haemolytica is the only pathogen that consistently causes severe bronchopneumonia and rapid death of bighorn sheep (BHS; Ovis canadensis) under experimental conditions. Paradoxically, Bibersteinia (Pasteurella) trehalosi and Pasteurella multocida have been isolated from BHS ...

  16. Bibersteinia trehalosi Inhibits the Growth of Mannheimia haemolytica by a Proximity-Dependent Mechanism

    USDA-ARS?s Scientific Manuscript database

    Mannheimia (Pasteurella) haemolytica is the only pathogen that consistently causes severe bronchopneumonia and rapid death of bighorn sheep (BHS; Ovis canadensis) under experimental conditions. Paradoxically, Bibersteinia (Pasteurella) trehalosi and occasionally Pasteurella multocida have been isola...

  17. Genome sequences of mannheimia haemolytica serotype A2: ovine and bovine isolates

    USDA-ARS?s Scientific Manuscript database

    This report describes the genome sequences of Mannheimia haemolytica, serotype A2 isolated from pneumonic lungs of two different ruminant species, one from Ovis aries, designated as Ovine (O) and the other from Bos taurus, designated as Bovine (B)....

  18. Proximity-dependent inhibition of growth of mannheimia haemolytica by pasteurella multocida.

    USDA-ARS?s Scientific Manuscript database

    Mannheimia haemolytica, Pasteurella multocida, and Bibersteinia trehalosi have been identified in the lungs of pneumonic bighorn sheep (BHS; Ovis canadensis). Of these pathogens, M. haemolytica has been shown to consistently cause fatal pneumonia in BHS under experimental conditions. However, M. hae...

  19. Identification of the pan and core genomes for Mannheimia haemolytica genotypes 1 and 2

    USDA-ARS?s Scientific Manuscript database

    Mannheimia haemolytica normally populates the upper respiratory tract of cattle and is recognized as a major cause of bovine respiratory disease. Recently, two major genotypes (1 and 2) of M. haemolytica were identified from whole genome sequencing and analyses of 1,145 North American isolates. On...

  20. Identification of a mannheimia haemolytica genetic subtype that causes bovine respiratory disease

    USDA-ARS?s Scientific Manuscript database

    Bovine respiratory disease complex (BRDC) is a serious health and economic problem that costs the United States cattle industry over a billion dollars annually. Mannheimia haemolytica is a major bacterial component of BRDC. An opportunistic pathogen, M. haemolytica resides within the upper respira...

  1. A multiplex PCR assay for molecular capsular serotyping of Mannheimia haemolytica serotypes 1, 2, and 6

    USDA-ARS?s Scientific Manuscript database

    Mannheimia haemolytica is an important respiratory pathogen of ruminants. Of the 12 capsular serovars identified, 1 and 6 are most frequently associated with disease in cattle, while 2 is largely a commensal. Comparative analysis of 24 M. haemolytica genomes was used to identify unique genes associa...

  2. Comparative Genomic Analysis of Mannheimia haemolytica from Bovine Sources

    PubMed Central

    Klima, Cassidy L.; Cook, Shaun R.; Zaheer, Rahat; Laing, Chad; Gannon, Vick P.; Xu, Yong; Rasmussen, Jay; Potter, Andrew; Hendrick, Steve; Alexander, Trevor W.; McAllister, Tim A.

    2016-01-01

    Bovine respiratory disease is a common health problem in beef production. The primary bacterial agent involved, Mannheimia haemolytica, is a target for antimicrobial therapy and at risk for associated antimicrobial resistance development. The role of M. haemolytica in pathogenesis is linked to serotype with serotypes 1 (S1) and 6 (S6) isolated from pneumonic lesions and serotype 2 (S2) found in the upper respiratory tract of healthy animals. Here, we sequenced the genomes of 11 strains of M. haemolytica, representing all three serotypes and performed comparative genomics analysis to identify genetic features that may contribute to pathogenesis. Possible virulence associated genes were identified within 14 distinct prophage, including a periplasmic chaperone, a lipoprotein, peptidoglycan glycosyltransferase and a stress response protein. Prophage content ranged from 2–8 per genome, but was higher in S1 and S6 strains. A type I-C CRISPR-Cas system was identified in each strain with spacer diversity and organization conserved among serotypes. The majority of spacers occur in S1 and S6 strains and originate from phage suggesting that serotypes 1 and 6 may be more resistant to phage predation. However, two spacers complementary to the host chromosome targeting a UDP-N-acetylglucosamine 2-epimerase and a glycosyl transferases group 1 gene are present in S1 and S6 strains only indicating these serotypes may employ CRISPR-Cas to regulate gene expression to avoid host immune responses or enhance adhesion during infection. Integrative conjugative elements are present in nine of the eleven genomes. Three of these harbor extensive multi-drug resistance cassettes encoding resistance against the majority of drugs used to combat infection in beef cattle, including macrolides and tetracyclines used in human medicine. The findings here identify key features that are likely contributing to serotype related pathogenesis and specific targets for vaccine design intended to reduce the

  3. Genome Sequence of a Spontaneous Nonhemolytic Mutant of Mannheimia haemolytica 16041065 GH

    PubMed Central

    Ayalew, Sahlu; Confer, Anthony W.; Hansen, Richard D.

    2017-01-01

    ABSTRACT We report here the draft genome sequence of a spontaneous nonhemolytic mutant of Mannheimia haemolytica 16041065 GH. This mutant arose during routine passage and was devoid of hemolytic activity on standard blood agars. This genome sequence had a total size of 2.7 Mb with an N50 of 117 kb. PMID:28385858

  4. Genome sequences of serotype A6 Mannheimia haemolytica isolates D174 and D38 recovered from bovine pneumonia

    USDA-ARS?s Scientific Manuscript database

    Here we report two genomes, one complete and one draft, from virulent bovine strains of Mannheimia haemolytica(strains D174 and D38)serotype A2 recovered prior to the field usage of modern antimicrobial drugs....

  5. Characterization of Mannheimia haemolytica in beef calves via nasopharyngeal culture and pulsed-field gel electrophoresis.

    PubMed

    Capik, Sarah F; White, Brad J; Lubbers, Brian V; Apley, Michael D; Mosier, Derek A; Larson, Robert L; Murray, Robert W

    2015-09-01

    Mannheimia haemolytica is a major bacterial component of bovine respiratory disease (BRD); unfortunately, very little is known about M. haemolytica transmission dynamics among cattle. Identifying potential variation in M. haemolytica populations over time and induction of nasopharyngeal colonization and subsequent shedding are 2 areas where knowledge is lacking. In our study, 2 separate loads of 20 mixed-origin, male calves were purchased through an order buyer on different dates. Deep nasopharyngeal cultures (NPC) were performed on all calves on arrival and, if M. haemolytica-negative, a second screening culture was obtained. Calves that were negative on 2 initial NPCs (NEG; n = 4) were subsequently challenged with a previously isolated field strain of M. haemolytica in both the upper and lower respiratory tract, individually housed, and then monitored for M. haemolytica shedding via NPCs at 0.5, 1, 3, 5, 7, and 9 days postchallenge. Naturally M. haemolytica-positive calves (2 per load) were kept for additional daily cultures (POS; n = 4). Individual calf M. haemolytica status for both the POS and NEG groups was inconsistent between study days. Additionally, pulsed-field gel electrophoresis performed on isolates from the positive cultures showed that the NEG calves did not shed the M. haemolytica challenge strain, but rather 2 distinct clusters of M. haemolytica were shared among POS and NEG calves regardless of their initial status. Although sample sizes were small, these findings illustrate how variable the results of a single nasopharyngeal swab can be and the challenges of using an individual culture to truly represent animal M. haemolytica status.

  6. LKTA and PlpE small fragments fusion protein protect against Mannheimia haemolytica challenge.

    PubMed

    Guzmán-Brambila, Carolina; Quintero-Fabián, Saray; González-Castillo, Celia; de Obeso-Fernández del Valle, Álvaro; Flores-Samaniego, Beatriz; de la Mora, Germán; Rojas-Mayorquín, Argelia E; Ortuño-Sahagún, Daniel

    2012-12-01

    Bovine respiratory disease (BRD) complex is a major cause of economic losses for the cattle backgrounding and feedlot industries. Mannheimia haemolytica is considered the most important pathogen associated with this disease. Vaccines against M. haemolytica have been prepared and used for many decades, but traditional bacterins have failed to demonstrate effective protection and their use has often exacerbated disease in vaccinated animals. Thus, the BRD complex continues to exert a strong adverse effect on the health and wellbeing of stocker and feeder cattle. Therefore, generation of recombinant proteins has been helpful in formulating enhanced vaccines against M. haemolytica, which could confer better protection against BRD. In the present study, we formulated a vaccine preparation enriched with recombinant small fragments of leukotoxin A (LKTA) and outer-membrane lipoprotein (PlpE) proteins, and demonstrated its ability to generate high antibody titers in rabbits and sheep, which protected against M. haemolytica bacterial challenge in mice.

  7. Mannheimia haemolytica and Its Leukotoxin Cause Neutrophil Extracellular Trap Formation by Bovine Neutrophils▿

    PubMed Central

    Aulik, Nicole A.; Hellenbrand, Katrina M.; Klos, Heather; Czuprynski, Charles J.

    2010-01-01

    Mannheimia haemolytica is an important member of the bovine respiratory disease complex, which is characterized by abundant neutrophil infiltration into the alveoli and fibrin deposition. Recently several authors have reported that human neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of trapping and killing pathogens. Here, we demonstrate that the leukotoxin (LKT) of M. haemolytica causes NET formation by bovine neutrophils in a CD18-dependent manner. Using an unacylated, noncytotoxic pro-LKT produced by an ΔlktC mutant of M. haemolytica, we show that binding of unacylated pro-LKT stimulates NET formation despite a lack of cytotoxicity. Inhibition of LKT binding to the CD18 chain of lymphocyte function-associated antigen 1 (LFA-1) on bovine neutrophils reduced NET formation in response to LKT or M. haemolytica cells. Further investigation revealed that NETs formed in response to M. haemolytica are capable of trapping and killing a portion of the bacterial cells. NET formation was confirmed by confocal microscopy and by scanning and transmission electron microscopy. Prior exposure of bovine neutrophils to LKT enhanced subsequent trapping and killing of M. haemolytica cells in bovine NETs. Understanding NET formation in response to M. haemolytica and its LKT provides a new perspective on how neutrophils contribute to the pathogenesis of bovine respiratory disease. PMID:20823211

  8. Mannheimia haemolytica and Its Leukotoxin Cause Macrophage Extracellular Trap Formation by Bovine Macrophages

    PubMed Central

    Aulik, Nicole A.; Hellenbrand, Katrina M.

    2012-01-01

    Human and bovine neutrophils release neutrophil extracellular traps (NETs), which are protein-studded DNA matrices capable of extracellular trapping and killing of pathogens. Recently, we reported that bovine neutrophils release NETs in response to the important respiratory pathogen Mannheimia haemolytica and its leukotoxin (LKT). Here, we demonstrate macrophage extracellular trap (MET) formation by bovine monocyte-derived macrophages exposed to M. haemolytica or its LKT. Both native fully active LKT and noncytolytic pro-LKT (produced by an lktC mutant of M. haemolytica) stimulated MET formation. Confocal and scanning electron microscopy revealed a network of DNA fibrils with colocalized histones in extracellular traps released from bovine macrophages. Formation of METs required NADPH oxidase activity, as previously demonstrated for NET formation. METs formed in response to LKT trapped and killed a portion of the M. haemolytica cells. Bovine alveolar macrophages, but not peripheral blood monocytes, also formed METs in response to M. haemolytica cells. MET formation was not restricted to bovine macrophages. We also observed MET formation by the mouse macrophage cell line RAW 264.7 and by human THP-1 cell-derived macrophages, in response to Escherichia coli hemolysin. The latter is a member of the repeats-in-toxin (RTX) toxin family related to the M. haemolytica leukotoxin. This study demonstrates that macrophages, like neutrophils, can form extracellular traps in response to bacterial pathogens and their exotoxins. PMID:22354029

  9. Complete Genome Sequence of Mannheimia haemolytica Strain Mh10517, Isolated from Sheep in South Africa.

    PubMed

    Kidanemariam Gelaw, Awoke; Bihon, Wubetu; Faranani, Ramagoma; Mafofo, Joseph; Rees, Jasper; Madoroba, Evelyn

    2015-04-09

    Respiratory disease caused by Mannheimia haemolytica is a major concern in the cattle and small stock industry worldwide. This problem arises due to the interaction of numerous contributing factors, including physical stresses associated with weaning, shipment, inclement weather, and overcrowding coupled with viral and bacterial infections. The whole genome of M. haemolytica strain Mh10517 was analyzed using an Illumina MiSeq high-throughput sequencing platform. The genome size is 2.67 Mb with 2,879 predicted gene sequences. The availability of this genome sequence will advance studies on various aspects of the biology of M. haemolytica in Africa and the world at large. Copyright © 2015 Kidanemariam Gelaw et al.

  10. Identification of immunodominant proteins from Mannheimia haemolytica and Histophilus somni by an immunoproteomic approach

    PubMed Central

    Alvarez, Angel H.; Gutiérrez-Ortega, Abel; Hernández-Gutiérrez, Rodolfo

    2015-01-01

    Mannheimia haemolytica and Histophilus somni are frequently isolated from diseased cattle with bovine respiratory disease (BRD). They compromise animal lung function and the immune responses generated are not sufficient to limit infection. Identification of specific immunogenic antigens for vaccine development represents a great challenge. Immunogenic proteins were identified by immunoproteomic approach with sera from cattle immunized with a commercial cellular vaccine of M. haemolytica and H. somni. Proteins of M. haemolytica were identified as solute ABC transporter, iron-binding protein, and hypothetical protein of capsular biosynthesis. Histophilus somni proteins correspond to porin, amino acid ABC transporter, hypothetical outer membrane protein, cysteine synthase, and outer membrane protein P6. Although these antigens share strong similarities with other proteins from animal pathogens, the ABC system proteins have been associated with virulence and these proteins could be considered as potential vaccine candidates for BRD. PMID:26424916

  11. Bighorn sheep × domestic sheep hybrids survive Mannheimia haemolytica challenge in the absence of vaccination.

    PubMed

    Subramaniam, R; Shanthalingam, S; Bavananthasivam, J; Kugadas, A; Raghavan, B; Batra, S A; Herndon, C N; Rodriguez, J; Tibary, A; Nelson, D; Potter, K A; Foreyt, W J; Srikumaran, S

    2014-06-04

    Bighorn sheep (BHS, Ovis canadensis) are much more susceptible than domestic sheep (DS, Ovis aries) to pneumonia caused by leukotoxin (Lkt)-producing members of the Family Pasteurellaceae, particularly Mannheimia haemolytica and Bibersteinia trehalosi. Leukotoxin is widely accepted as the critical virulence factor of these bacteria since Lkt-negative mutants do not cause death of BHS. Typically, DS carry Lkt-positive M. haemolytica and/or B. trehalosi as commensal bacteria in their nasopharynx. In contrast, most BHS do not carry Lkt-positive M. haemolytica or B. trehalosi, or carry Lkt-negative strains in their nasopharynx. In previous studies, we demonstrated that unimmunized DS resist M. haemolytica challenge while BHS succumb to it. We hypothesized that Lkt-neutralizing antibodies, induced by Lkt-positive M. haemolytica and/or B. trehalosi innately carried by DS in their nasopharynx, render them less susceptible to infection by these bacteria. In this study we developed BHS×DS F1 hybrids by artificial insemination of domestic ewes with BHS semen. F1 hybrids were fertile, and produced F2 hybrids and back-crosses. The F1, F2, and back-crosses were raised together with domestic ewes. All these animals acquired Lkt-positive M. haemolytica and/or B. trehalosi, and developed high titers of Lkt-neutralizing antibodies in the absence of vaccination. Furthermore, all of these animals resisted challenge with lethal dose of M. haemolytica. These results suggest that lack of previous exposure to Lkt is at least partially responsible for fatal pneumonia in BHS when they acquire Lkt-positive M. haemolytica and/or B. trehalosi from DS when the two species commingle.

  12. Ovis aries CR4 is involved in Mannheimia haemolytica leukotoxin-induced cytotoxicity.

    PubMed

    Lawrence, Paulraj K; Dassanayake, Rohana P

    2010-06-15

    Pneumonia caused by Mannheimia haemolytica is an important disease of domestic sheep (DS, Ovis aries) and cattle (BO). M. haemolytica is a normal commensal of the upper respiratory tract in ruminants, but during stress and viral infection it breaches the host innate mucosal defense and descents into lungs causing fibrinous pleuropneumonia. Leukotoxin (Lkt) produced by M. haemolytica is cytolytic to all subsets of ruminant leukocytes. Earlier, we and others have shown that DS and BO LFA-1 (CD11a/CD18) and Mac-1 (CD11b/CD18) can mediate Lkt-induced cytolysis. It is not clear whether CR4 (CD11c/CD18), which is involved in chemotaxis, phagocytosis and regulates host immune response can also mediate Lkt-induced cytolysis in ruminants. The host innate immune response to M. haemolytica is poorly understood and the involvement of CR4 in M. haemolytica pathogenesis is one of the most understudied. This problem is further compounded by the lack of cd11c genes from any ruminant species. Therefore, the objectives of this study were to clone cd11c and determine whether CR4 can serve as a receptor for Lkt. In this direction we cloned two alleles of cd11c gene from leukocytes isolated from DS blood by RT-PCR. Transfectants developed expressing functional DS CR4 were found to be cytotoxic to Lkt from four different isolates of M. haemolytica. This is the first report confirming the ability of a recombinant ovine CR4 to bind to M. haemolytica Lkt and mediate concentration-dependent lysis of host cells, thus, confirming their role in M. haemolytica pathogenesis. This is a critical step in understanding host innate immunity and the management of pneumonia in sheep. Copyright 2009 Elsevier B.V. All rights reserved.

  13. Mycoplasma ovipneumoniae can predispose bighorn sheep to fatal Mannheimia haemolytica pneumonia.

    PubMed

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Herndon, Caroline N; Subramaniam, Renuka; Lawrence, Paulraj K; Bavananthasivam, Jegarubee; Cassirer, E Frances; Haldorson, Gary J; Foreyt, William J; Rurangirwa, Fred R; Knowles, Donald P; Besser, Thomas E; Srikumaran, Subramaniam

    2010-10-26

    Mycoplasma ovipneumoniae has been isolated from the lungs of pneumonic bighorn sheep (BHS). However experimental reproduction of fatal pneumonia in BHS with M. ovipneumoniae was not successful. Therefore the specific role, if any, of M. ovipneumoniae in BHS pneumonia is unclear. The objective of this study was to determine whether M. ovipneumoniae alone causes fatal pneumonia in BHS, or predisposes them to infection by Mannheimia haemolytica. We chose M. haemolytica for this study because of its isolation from pneumonic BHS, and its consistent ability to cause fatal pneumonia under experimental conditions. Since in vitro culture could attenuate virulence of M. ovipneumoniae, we used ceftiofur-treated lung homogenates from pneumonic BHS lambs or nasopharyngeal washings from M. ovipneumoniae-positive domestic sheep (DS) as the source of M. ovipneumoniae. Two adult BHS were inoculated intranasally with lung homogenates while two others received nasopharyngeal washings from DS. All BHS developed clinical signs of respiratory infection, but only one BHS died. The dead BHS had carried leukotoxin-positive M. haemolytica in the nasopharynx before the onset of this study. It is likely that M. ovipneumoniae colonization predisposed this BHS to fatal infection with the M. haemolytica already present in this animal. The remaining three BHS developed pneumonia and died 1-5 days following intranasal inoculation with M. haemolytica. On necropsy, lungs of all four BHS showed lesions characteristic of bronchopneumonia. M. haemolytica and M. ovipneumoniae were isolated from the lungs. These results suggest that M. ovipneumoniae alone may not cause fatal pneumonia in BHS, but can predispose them to fatal pneumonia due to M. haemolytica infection. Copyright © 2010 Elsevier B.V. All rights reserved.

  14. Differential susceptibility of bighorn sheep and domestic sheep neutrophils to Mannheimia haemolytica leukotoxin is not due to differential expression of cell surface CD18

    USDA-ARS?s Scientific Manuscript database

    Bighorn sheep (BHS) are more susceptible to pneumonia caused by Mannheimia haemolytica (M. haemolytica) than are domestic sheep (DS). Leukotoxin produced by M. haemolytica is accepted as the critical virulence factor for BHS, based on the fact that Lkt-deletion mutants do not cause death of BHS. Al...

  15. Characterization of Mannheimia haemolytica isolated from feedlot cattle that were healthy or treated for bovine respiratory disease.

    PubMed

    Klima, Cassidy L; Alexander, Trevor W; Hendrick, Steve; McAllister, Tim A

    2014-01-01

    Mannheimia haemolytica is the principal bacterial pathogen associated with bovine respiratory disease (BRD). As an opportunistic pathogen, M. haemolytica is also frequently isolated from the respiratory tract of healthy cattle. This study examined the characteristics of M. haemolytica collected using deep nasal swabs from healthy cattle (n = 49) and cattle diagnosed with BRD (n = 41). Isolates were analyzed by pulsed-field gel electrophoresis (PFGE), serotyped, and tested for antimicrobial susceptibility. Polymerase chain reaction (PCR) was used to screen isolates for virulence [leukotoxin C (lktC), putative adhesin (ahs), outer-membrane lipoprotein (gs60), O-sialoglycoprotease (gcp), transferring-binding protein B (tbpB) and UDP-N-acetyl-D-glucosamine-2-epimerase (nmaA)] and antimicrobial resistance [tet(H), bla ROB-1, erm(X), erm(42), msr(E)-mph(E) and aphA-1] genes. Isolates were genetically diverse but in three instances, M. haemolytica with the same pulsotype, resistance phenotype, and genotype were collected from cattle with BRD. This occurred once between cattle located in two different feedlots, once between cattle in the same feedlot, but in different pens, and once among cattle from the same feedlot in the same pen. Isolates from healthy cattle were primarily serotype 2 (75.5%) while those from individuals with BRD were serotype 1 (70.7%) or 6 (19.5%). Resistance to at least one antibiotic occurred more frequently (P < 0.001) in M. haemolytica collected from cattle with BRD (37%) compared with those that were healthy (2%). Overall, tetracycline resistance (18%) was the most prevalent resistant phenotype. All tetracycline-resistant M. haemolytica encoded tet(H). Ampicillin resistance (6%) and neomycin resistance (15%) were detected and corresponded to the presence of the bla ROB-1 and aphA-1 genes, respectively. Tilmicosin resistance (6%) was also detected, but the resistance genes responsible were not identified. The virulence genes lktC, ahs, gs60, and

  16. Characterization of Mannheimia haemolytica isolated from feedlot cattle that were healthy or treated for bovine respiratory disease

    PubMed Central

    Klima, Cassidy L.; Alexander, Trevor W.; Hendrick, Steve; McAllister, Tim A.

    2014-01-01

    Mannheimia haemolytica is the principal bacterial pathogen associated with bovine respiratory disease (BRD). As an opportunistic pathogen, M. haemolytica is also frequently isolated from the respiratory tract of healthy cattle. This study examined the characteristics of M. haemolytica collected using deep nasal swabs from healthy cattle (n = 49) and cattle diagnosed with BRD (n = 41). Isolates were analyzed by pulsed-field gel electrophoresis (PFGE), serotyped, and tested for antimicrobial susceptibility. Polymerase chain reaction (PCR) was used to screen isolates for virulence [leukotoxin C (lktC), putative adhesin (ahs), outer-membrane lipoprotein (gs60), O-sialoglycoprotease (gcp), transferring-binding protein B (tbpB) and UDP-N-acetyl-D-glucosamine-2-epimerase (nmaA)] and antimicrobial resistance [tet(H), blaROB-1, erm(X), erm(42), msr(E)-mph(E) and aphA-1] genes. Isolates were genetically diverse but in three instances, M. haemolytica with the same pulsotype, resistance phenotype, and genotype were collected from cattle with BRD. This occurred once between cattle located in two different feedlots, once between cattle in the same feedlot, but in different pens, and once among cattle from the same feedlot in the same pen. Isolates from healthy cattle were primarily serotype 2 (75.5%) while those from individuals with BRD were serotype 1 (70.7%) or 6 (19.5%). Resistance to at least one antibiotic occurred more frequently (P < 0.001) in M. haemolytica collected from cattle with BRD (37%) compared with those that were healthy (2%). Overall, tetracycline resistance (18%) was the most prevalent resistant phenotype. All tetracycline-resistant M. haemolytica encoded tet(H). Ampicillin resistance (6%) and neomycin resistance (15%) were detected and corresponded to the presence of the blaROB-1 and aphA-1 genes, respectively. Tilmicosin resistance (6%) was also detected, but the resistance genes responsible were not identified. The virulence genes lktC, ahs, gs60, and gcp

  17. Probiotic bacteria inhibit the bovine respiratory pathogen Mannheimia haemolytica serotype 1 in vitro.

    PubMed

    Amat, S; Subramanian, S; Timsit, E; Alexander, T W

    2017-05-01

    This study evaluated the potential of probiotic bacteria to inhibit growth and cell adhesion of the bovine respiratory pathogen Mannheimia haemoltyica serotype 1. The inhibitory effects of nine probiotic strains (Lactobacillus acidophilus, Lactobacillus casei, Lactobacillus helveticus, Lactobacillus plantarum, Lactobacillus rhamnosus, Lactococcus lactis, Streptococcus thermophilus and two Paenibacillus polymyxa strains) against M. haemolytica were evaluated using a spot-on-lawn method. Probiotic strains were then tested for their adherence to bovine bronchial epithelial (BBE) cells and the ability to displace and compete against M. haemolytica on BBE. Except for S. thermophilus, all probiotic strains inhibited the growth of M. haemolytica, with zones of inhibition ranging between 12 and 19 mm. Lactobacillus strains and Lactococcus lactis displayed greater (P < 0·05) BBE adhesion compared with M. heamolytica (8·3%) and other probiotics (<2·2%). Strains of P. polymyxa and L. acidophilus caused the greatest reduction in M. haemolytica adherence, through both displacement and competition, compared with other probiotics. The results of this study suggest that probiotics may have the potential to colonize the bovine respiratory tract, and exert antagonistic effects against M. haemolytica serotype 1. A common method to control bovine respiratory disease (BRD) in feedlots is through mass medication with antibiotics upon cattle entry (i.e. metaphylaxis). Increasingly, antimicrobial resistance in BRD bacterial pathogens has been observed in feedlots, which may have important implications for cattle health. In this study, probiotic strains were shown to adhere to bovine respiratory cells and inhibit the BRD pathogen M. haemolytica serotype 1 through competition and displacement. Probiotics may therefore offer a mitigation strategy to reduce BRD bacterial pathogens, in place of metaphylactic antimicrobials. © 2017 Her Majesty the Queen in Right of Canada

  18. Defective bacterial clearance is responsible for the enhanced lung pathology characteristic of Mannheimia haemolytica pneumonia in bighorn sheep

    USDA-ARS?s Scientific Manuscript database

    The molecular and cellular basis for the enhanced lung pathology and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS, Ovis canadenesis), in comparison to domestic sheep (DS, Ovis aries), is not clear. Polymorphonuclear leukocytes (PMNs) of BHS are four- to eight-fold more susceptibl...

  19. Immunohistochemical detection of Mannheimia (Pasteurella) haemolytica antigens in goats with natural pneumonia.

    PubMed

    Yener, Z; Ilhan, F; Ilhan, Z; Saglam, Y S

    2009-04-01

    Pneumonia is a leading cause of loss to ruminants throughout the world. Mannheimia (Pasteurella) haemolytica is one of the most important etiological agent of pneumonia in cattle, sheep, and goats. This study was carried out to determine the incidence of M.haemolytica antigens using immunohistochemistry labelling of formalin-fixed, paraffin-embedded tissues in pneumonic lungs of goats slaughtered at abattoir, and then to compare these immunohistochemistry results with the results of bacterial isolation. For these objectives, a total of 1505 goat lungs slaughtered in slaughterhouse were grossly examined and pneumonia was detected in 74 cases (4.91%). Of these, with the exception of verminous pneumonia observed in 32 cases, on 42 pneumonic lungs immunohistochemical examinations were performed. Formalin-fixed and paraffin-embedded lung tissue samples were immunohistochemically stained by the avidin-biotin-peroxidase complex (ABC) procedure using polyclonal antibodies to detect M.haemolytica antigens. Pneumonic lesions were more frequently encountered in cranioventral lobes than caudal lobes, and characterized by irregular lobular foci of atelectasis or lobar pneumonia. The presence of M.haemolytica antigens was detected in 19 (45%) out of 42 pneumonic lungs. Bacterial antigens were found most frequently in the cytoplasm of bronchial and bronchiolar epithelial cells, in the swirling degenerating leukocytes in the alveoli, and in the degenerating leukocytes in the area of coagulation necrosis, less frequently in the epithelial cells of bronchial glands, and lymphoid cells. Conclusionly, immunohistochemical detection of M.haemolytica antigens in pneumonic lungs appear to be more reliable compared to bacterial isolation.

  20. Serum Headspace Analysis With An Electronic Nose And Comparison With Clinical Signs Following Experimental Infection Of Cattle With Mannheimia Haemolytica

    NASA Astrophysics Data System (ADS)

    Knobloch, Henri; Turner, Claire; Chambers, Mark; Reinhold, Petra

    2009-05-01

    Electronic noses (e-noses) have been widely used for medical applications or in the food industry. However, little is known about their utility for early disease detection in animals. In this study, 20 calves were experimentally infected with Mannheimia haemolytica A1. Blood serum was collected from 7 days before infection to 5 days after infection and headspace of sera was analysed using the ST214 (Scensive Tech. Ltd., Leeds, UK) e-nose. Differences between pre- and post infection status were investigated and a temporal profile of sensor responses was compared with body temperature over the course of infection. A similar profile for sensor responses and body temperature indicated the e-nose was detecting a genuine physiological response following infection.

  1. A three-way comparative genomic analysis of Mannheimia haemolytica isolates

    PubMed Central

    2010-01-01

    Background Mannhemia haemolytica is a Gram-negative bacterium and the principal etiological agent associated with bovine respiratory disease complex. They transform from a benign commensal to a deadly pathogen, during stress such as viral infection and transportation to feedlots and cause acute pleuropneumonia commonly known as shipping fever. The U.S beef industry alone loses more than one billion dollars annually due to shipping fever. Despite its enormous economic importance there are no specific and accurate genetic markers, which will aid in understanding the pathogenesis and epidemiology of M. haemolytica at molecular level and assist in devising an effective control strategy. Description During our comparative genomic sequence analysis of three Mannheimia haemolytica isolates, we identified a number of genes that are unique to each strain. These genes are "high value targets" for future studies that attempt to correlate the variable gene pool with phenotype. We also identified a number of high confidence single nucleotide polymorphisms (hcSNPs) spread throughout the genome and focused on non-synonymous SNPs in known virulence genes. These SNPs will be used to design new hcSNP arrays to study variation across strains, and will potentially aid in understanding gene regulation and the mode of action of various virulence factors. Conclusions During our analysis we identified previously unknown possible type III secretion effector proteins, clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated sequences (Cas). The presence of CRISPR regions is indicative of likely co-evolution with an associated phage. If proven functional, the presence of a type III secretion system in M. haemolytica will help us re-evaluate our approach to study host-pathogen interactions. We also identified various adhesins containing immuno-dominant domains, which may interfere with host-innate immunity and which could potentially serve as effective vaccine

  2. Transfection of non-susceptible cells with Ovis aries recombinant lymphocyte function-associated antigen 1 renders susceptibility to Mannheimia haemolytica leukotoxin

    USDA-ARS?s Scientific Manuscript database

    Mannheimia haemolytica is an important etiological agent of pneumonia in domestic sheep (DS, Ovis aries). Leukotoxin (Lkt) produced by this organism is the principal virulence factor responsible for the acute inflammation and lung injury characteristic of M. haemolytica caused disease. Previously, w...

  3. Precise gene editing paves the way for derivation of Mannheimia haemolytica leukotoxin-resistant cattle.

    PubMed

    Shanthalingam, Sudarvili; Tibary, Ahmed; Beever, Jonathan E; Kasinathan, Poothapillai; Brown, Wendy C; Srikumaran, Subramaniam

    2016-11-15

    Signal peptides of membrane proteins are cleaved by signal peptidase once the nascent proteins reach the endoplasmic reticulum. Previously, we reported that, contrary to the paradigm, the signal peptide of ruminant CD18, the β subunit of β2 integrins, is not cleaved and hence remains intact on mature CD18 molecules expressed on the surface of ruminant leukocytes. Leukotoxin secreted by Mannheimia (Pasteurella) haemolytica binds to the intact signal peptide and causes cytolysis of ruminant leukocytes, resulting in acute inflammation and lung tissue damage. We also demonstrated that site-directed mutagenesis leading to substitution of cleavage-inhibiting glutamine (Q), at amino acid position 5 upstream of the signal peptide cleavage site, with cleavage-inducing glycine (G) results in the cleavage of the signal peptide and abrogation of leukotoxin-induced cytolysis of target cells. In this proof-of-principle study, we used precise gene editing to induce Q(‒5)G substitution in both alleles of CD18 in bovine fetal fibroblast cells. The gene-edited fibroblasts were used for somatic nuclear transfer and cloning to produce a bovine fetus homozygous for the Q(‒5)G substitution. The leukocyte population of this engineered ruminant expressed CD18 without the signal peptide. More importantly, these leukocytes were absolutely resistant to leukotoxin-induced cytolysis. This report demonstrates the feasibility of developing lines of cattle genetically resistant to M. haemolytica-caused pneumonia, which inflicts an economic loss of over $1 billion to the US cattle industry alone.

  4. Differences in susceptibility to Mannheimia haemolytica-associated mastitis between two breeds of dairy sheep.

    PubMed

    Fragkou, Ilectra A; Skoufos, John; Cripps, Peter J; Kyriazakis, Ilias; Papaioannou, Nikos; Boscos, Costas M; Tzora, Athina; Fthenakis, George C

    2007-08-01

    We used a Mannheimia haemolytica isolate to study differences in susceptibility to experimental mastitis between two breeds of dairy sheep. The isolate was deposited into the teat duct of Karagouniko (K, n=8) or Frisarta (F, n=8) ewes. The animals were monitored by means of clinical, bacteriological, cytological and pathological methods. K ewes did not develop any systemic or mammary clinical signs, whilst F ewes became ill and developed acute clinical mastitis 12 h later (P<0.001). Bacteria were isolated from 34/48 samples from K ewes and from 46/46 samples from F ewes. Positive California mastitis test (CMT) results were 17/24 samples from K ewes and 23/23 samples from F ewes; leucocytes were seen in Giemsa-stained films. Total pathology score summed over all group K ewes was 41 (maximum possible: 128); Man. haemolytica was isolated from 12/24 tissue samples. Total pathology score summed over all group F ewes was 93; Man. haemolytica was isolated from 24/24 tissue samples. Hyperplastic lymphoid nodules consisting of lymphocytes and plasma cells with germinal activity were characteristically present at the border between teat duct-teat cistern of group K ewes; no such structures were observed in teats of group F ewes. The results identified differences in susceptibility/resistance to a mastitis pathogen among animals of the two breeds. Defence mechanisms of the teat appeared to be inadequate against the invading organisms; as lymphoid nodules have been considered important defensive mechanisms of the ovine teat, their observed lack in Frisarta ewes might have predisposed them to development of mastitis.

  5. Precise gene editing paves the way for derivation of Mannheimia haemolytica leukotoxin-resistant cattle

    PubMed Central

    Shanthalingam, Sudarvili; Tibary, Ahmed; Beever, Jonathan E.; Kasinathan, Poothapillai; Brown, Wendy C.; Srikumaran, Subramaniam

    2016-01-01

    Signal peptides of membrane proteins are cleaved by signal peptidase once the nascent proteins reach the endoplasmic reticulum. Previously, we reported that, contrary to the paradigm, the signal peptide of ruminant CD18, the β subunit of β2 integrins, is not cleaved and hence remains intact on mature CD18 molecules expressed on the surface of ruminant leukocytes. Leukotoxin secreted by Mannheimia (Pasteurella) haemolytica binds to the intact signal peptide and causes cytolysis of ruminant leukocytes, resulting in acute inflammation and lung tissue damage. We also demonstrated that site-directed mutagenesis leading to substitution of cleavage-inhibiting glutamine (Q), at amino acid position 5 upstream of the signal peptide cleavage site, with cleavage-inducing glycine (G) results in the cleavage of the signal peptide and abrogation of leukotoxin-induced cytolysis of target cells. In this proof-of-principle study, we used precise gene editing to induce Q(‒5)G substitution in both alleles of CD18 in bovine fetal fibroblast cells. The gene-edited fibroblasts were used for somatic nuclear transfer and cloning to produce a bovine fetus homozygous for the Q(‒5)G substitution. The leukocyte population of this engineered ruminant expressed CD18 without the signal peptide. More importantly, these leukocytes were absolutely resistant to leukotoxin-induced cytolysis. This report demonstrates the feasibility of developing lines of cattle genetically resistant to M. haemolytica-caused pneumonia, which inflicts an economic loss of over $1 billion to the US cattle industry alone. PMID:27799556

  6. New interpretive criteria for danofloxacin antibacterial susceptibility testing against Mannheimia haemolytica and Pasteurella multocida associated with bovine respiratory disease.

    PubMed

    Sweeney, Michael T; Papich, Mark G; Watts, Jeffrey L

    2017-03-01

    Danofloxacin is a fluoroquinolone antibacterial agent approved for use in veterinary medicine to treat and control bovine respiratory disease caused by Mannheimia haemolytica or Pasteurella multocida. Susceptible minimal inhibitory concentration (MIC) breakpoint (≤0.25 µg/mL) and disk diffusion interpretive criteria (≥22 mm) values for danofloxacin against M. haemolytica and P. multocida were first approved by the Clinical and Laboratory Standards Institute (CLSI) in 2003. However, intermediate and resistant breakpoint values were not established because only susceptible wild-type populations were evident at the time of breakpoint approvals. Since then, nonsusceptible isolates of M. haemolytica and P. multocida have been identified. We report danofloxacin intermediate MIC breakpoint (0.5 µg/mL) and disk diffusion interpretive criteria (18-21 mm), as well as danofloxacin-resistant MIC breakpoint (≥1 µg/mL) and disk diffusion interpretive criteria (≤17 mm), based on scattergram plots of MIC values versus disk zone diameters and calculated error-bound rates using M. haemolytica and P. multocida isolates recovered from bovine respiratory disease in North America in 2004-2014. These newly established intermediate and resistant clinical breakpoint values have been endorsed by CLSI and can be used for interpreting results from antibacterial susceptibility testing of danofloxacin against M. haemolytica and P. multocida isolated from bovine respiratory disease.

  7. Antimicrobial resistance and genetic characterization of fluoroquinolone-resistant Mannheimia haemolytica isolates from cattle with bovine pneumonia.

    PubMed

    Katsuda, Ken; Kohmoto, Mariko; Mikami, Osamu; Uchida, Ikuo

    2009-10-20

    Antimicrobial susceptibility and molecular characterization of quinolone-resistant Mannheimia haemolytica was conducted. The antimicrobial susceptibility of 229 M. haemolytica isolates which were obtained from cattle with bovine respiratory disease during the period 1984-2006, was determined using 14 antimicrobial agents. Of the 229 isolates, 114 (49.8%) were resistant to at least one agent and resistance rates ranged from 4.8% to 31.4%. Resistance rates for dihydrostreptomycin, oxytetracycline, doxycycline, ampicillin, amoxicillin, thiamphenicol, kanamycin chloramphenicol, nalidixic acid, enrofloxacin, and danofloxacin were 31.4%, 20.5%, 18.3%, 19.2%, 16.6%, 10.9%, 11.4%, 10.5%, 17.0%, 4.8% and 4.8%, respectively. The nucleotide sequences of the quinolone resistance-determining regions of the gyrA and parC genes of nalidixic acid-resistant M. haemolytica were determined. All nalidixic acid-resistant strains possessed at least one amino acid substitution in each of the GyrA and ParC fragments investigated. These results suggest that M. haemolytica require at least one amino acid substitution in both GyrA and ParC in order to attain significant levels of resistance to quinolones. All fluoroquinolone-resistant isolates belonged to serotype 6, and their genotype by PFGE analysis was identical. This result indicates that fluoroquinolone-resistant M. haemolytica strains have clonally expanded.

  8. Effect of subtherapeutic vs. therapeutic administration of macrolides on antimicrobial resistance in Mannheimia haemolytica and enterococci isolated from beef cattle

    PubMed Central

    Zaheer, Rahat; Cook, Shaun R.; Klima, Cassidy L.; Stanford, Kim; Alexander, Trevor; Topp, Edward; Read, Ron R.; McAllister, Tim A.

    2013-01-01

    Macrolides are the first-line treatment against bovine respiratory disease (BRD), and are also used to treat infections in humans. The macrolide, tylosin phosphate, is often included in the diet of cattle as a preventative for liver abscesses in many regions of the world outside of Europe. This study investigated the effects of administering macrolides to beef cattle either systemically through a single subcutaneous injection (therapeutic) or continuously in-feed (subtherapeutic), on the prevalence and antimicrobial resistance of Mannheimia haemolytica and Enterococcus spp. isolated from the nasopharynx and faeces, respectively. Nasopharyngeal and faecal samples were collected weekly over 28 days from untreated beef steers and from steers injected once with tilmicosin or tulathromycin or continuously fed tylosin phosphate at dosages recommended by manufacturers. Tilmicosin and tulathromycin were effective in lowering (P < 0.05) the prevalence of M. haemolytica, whereas subtherapeutic tylosin had no effect. M. haemolytica isolated from control- and macrolide-treated animals were susceptible to macrolides as well as to other antibiotics. Major bacteria co-isolated with M. haemolytica from the nasopharynx included Pasteurella multocida, Staphylococcus spp., Acinetobacter spp., Escherichia coli and Bacillus spp. With the exception of M. haemolytica and P. multocida, erythromycin resistance was frequently found in other isolated species. Both methods of macrolide administration increased (P < 0.05) the proportion of erythromycin resistant enterococci within the population, which was comprised almost exclusively of Enterococcus hirae. Injectable macrolides impacted both respiratory and enteric microbes, whereas orally administered macrolides only influenced enteric bacteria. PMID:23750157

  9. Defective bacterial clearance is responsible for the enhanced lung pathology characteristic of Mannheimia haemolytica pneumonia in bighorn sheep.

    PubMed

    Subramaniam, Renuka; Herndon, Caroline N; Shanthalingam, Sudarvili; Dassanayake, Rohana P; Bavananthasivam, Jegarubee; Potter, Kathleen A; Knowles, Donald P; Foreyt, William J; Srikumaran, Subramaniam

    2011-12-15

    The molecular and cellular basis for the enhanced lung pathology and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS, Ovis canadenesis), in comparison to domestic sheep (DS, Ovis aries), is not clear. Polymorphonuclear leukocytes (PMNs) of BHS are four- to eight-fold more susceptible to M. haemolytica leukotoxin-induced cytolysis, which is likely to reduce the number of functional phagocytes in the lung. We hypothesized that enhanced lung pathology is due to defective clearance of M. haemolytica from the lungs of BHS. To test this hypothesis, M. haemolytica (1 × 10(7) colony forming units [cfu]) were inoculated intra-tracheally into three groups each of BHS and DS, which were euthanized and necropsied at 4, 12, and 18 h post-inoculation (hpi). Bacterial and leukocyte counts were performed on broncho-alveolar lavage fluid (BALF) collected at necropsy. BALF from BHS euthanized at 4 and 12 hpi contained a significantly higher number of M. haemolytica than that from DS. More importantly, DS did not have any bacteria in BALF at 18 hpi, while the BHS still had significant numbers. As expected, the BHS did exhibit more extensive lung lesions at 12 and 18 hpi when compared to DS. At 18 hpi, necrotic PMNs were observed in the lesional lung tissues of BHS, but not DS. Furthermore, BALF from BHS had significantly lower titers of antibodies to Lkt and surface antigens of M. haemolytica, than that of DS. These findings suggest that the enhanced pathology in BHS lungs is due to defective clearance of M. haemolytica from the lungs. Copyright © 2011 Elsevier B.V. All rights reserved.

  10. Biochemical Characterization of a Polysialyltransferase from Mannheimia haemolytica A2 and Comparison to Other Bacterial Polysialyltransferases

    PubMed Central

    Lindhout, Theresa; Bainbridge, Cynthia R.; Costain, Will J.; Gilbert, Michel; Wakarchuk, Warren W.

    2013-01-01

    Polysialic acids are bioactive carbohydrates found in eukaryotes and some bacterial pathogens. The bacterial polysialyltransferases (PSTs), which catalyze the synthesis of polysialic acid capsules, have previously been identified in select strains of Escherichia coli and Neisseria meningitidis and are classified in the Carbohydrate-Active enZYmes Database as glycosyltransferase family GT-38. In this study using DNA sequence analysis and functional characterization we have identified a novel polysialyltransferase from the bovine/ovine pathogen Mannheimia haemolytica A2 (PSTMh). The enzyme was expressed in recombinant form as a soluble maltose-binding-protein fusion in parallel with the related PSTs from E. coli K1 and N. meningitidis group B in order to perform a side-by-side comparison. Biochemical properties including solubility, acceptor preference, reaction pH optima, thermostability, kinetics, and product chain length for the enzymes were compared using a synthetic fluorescent acceptor molecule. PSTMh exhibited biochemical properties that make it an attractive candidate for chemi-enzymatic synthesis applications of polysialic acid. The activity of PSTMh was examined on a model glycoprotein and the surface of a neuroprogenitor cell line where the results supported its development for use in applications to therapeutic protein modification and cell surface glycan remodelling to enable cell migration at implantation sites to promote wound healing. The three PSTs examined here demonstrated different properties that would each be useful to therapeutic applications. PMID:23922842

  11. Pharmacokinetic and Pharmacodynamic Profiles of Danofloxacin Administered by Two Dosing Regimens in Calves Infected with Mannheimia (Pasteurella) haemolytica

    PubMed Central

    Sarasola, Patxi; Lees, Peter; Shojaee AliAbadi, Fariborz; McKellar, Quintin A.; Donachie, William; Marr, Kate A.; Sunderland, Simon J.; Rowan, Tim G.

    2002-01-01

    The pharmacokinetics and pharmacodynamics of danofloxacin in calves with induced Mannheimia (Pasteurella) haemolytica pneumonia were evaluated. Calves received either saline as an intravenous (IV) bolus or danofloxacin (0.738 mg/kg of body weight) administered as either a single IV bolus or a 36-h continuous IV infusion. Blood samples and bronchial secretions were collected before and at predetermined times over 48 h following the start of treatment. Calves were assessed clinically throughout, and lung consolidation was assessed at necropsy. Bronchial secretions and lung tissue were cultured for M. haemolytica. Bolus administration of danofloxacin produced a high maximum drug concentration-to-MIC ratio (Cmax:MIC) of 14.5 and a time period of 9.1 h when plasma danofloxacin concentrations exceeded the MIC (T>MIC). Following danofloxacin infusion, the Cmax:MIC was low (2.3), with a long T>MIC (33.3 h). The area under the curve-to-MIC ratios were 43.3 and 49.1 for the bolus and infusion administrations, respectively. The single bolus of danofloxacin was more effective than the same dose administered by continuous infusion, as indicated by a significantly lower (P < 0.05) number of animals with M. haemolytica in bronchial secretions after treatment and lower rectal temperatures in the 24 h after the start of treatment. Thus, danofloxacin exhibited concentration-dependent antimicrobial activity in cattle with respiratory disease caused by M. haemolytica. PMID:12183261

  12. Impact of Timing and Dosage of a Fluoroquinolone Treatment on the Microbiological, Pathological, and Clinical Outcomes of Calves Challenged with Mannheimia haemolytica

    PubMed Central

    Lhermie, Guillaume; Ferran, Aude A.; Assié, Sébastien; Cassard, Hervé; El Garch, Farid; Schneider, Marc; Woerhlé, Frédérique; Pacalin, Diane; Delverdier, Maxence; Bousquet-Mélou, Alain; Meyer, Gilles

    2016-01-01

    The efficacy of an early and low inoculum-adjusted marbofloxacin treatment was evaluated on microbiological and clinical outcomes in calves infected with 4.107 CFU of Mannheimia haemolytica A1. Twenty-two calves were included based on their rectal temperature rise in the 10 h after challenge and allocated in four groups, receiving a single intramuscular injection of saline (CON), 2 mg/kg marbofloxacin 2–4 h after inclusion (early treatment, E2), 2 or 10 mg/kg marbofloxacin 35–39 h after inclusion (late treatments, L2, L10). In CON calves, M. haemolytica DNA loads in bronchoalveolar lavages continuously increased from inclusion to day 4, and were associated with persistent respiratory clinical signs and lung lesions. At times of early and late treatments, M. haemolytica loads ranged within 3.5–4 and 5.5–6 log10 DNA copies/mL, respectively. Early 2 mg/kg marbofloxacin treatment led to rapid and total elimination of bacteria in all calves. The late treatments induced a reduction of bacterial loads, but 3 of 6 L2 and 1 of 6 L10 calves were still positive for M. haemolytica at day 4. Except for CON calves, all animals exhibited clinical improvement within 24 h after treatment. However, early 2 mg/kg treatment was more efficacious to prevent pulmonary lesions, as indicated by the reduction of the extension and severity of gross lesions and by the histopathological scores. These results demonstrated for the first time that a reduced antibiotic regimen given at an early stage of the disease and targeting a low bacterial load could be efficacious in a natural bovine model of pneumonia. PMID:26973615

  13. Genomic signatures of Mannheimia haemolytica that associate with the lungs of cattle with respiratory disease, an integrative conjugative element, and antibiotic resistance genes

    USDA-ARS?s Scientific Manuscript database

    Background: Mannheimia haemolytica typically resides in cattle as a commensal member of the upper respiratory tract microbiome. However, some strains can invade their lungs and cause respiratory disease and death, including those with multi-drug resistance. A nucleotide polymorphism typing system ...

  14. Mucosal and parenteral vaccination against pneumonic pasteurellosis in cattle with a modified-live in-frame lktA deletion mutant of Mannheimia haemolytica

    USDA-ARS?s Scientific Manuscript database

    A new temperature-conditional shuttle vector, pBB80C, was constructed and utilized to generate an in-frame deletion in the leukotoxin structural gene of Mannheimia haemolytica serotype 1. Culture supernatants from the mutant contained no detectable cytotoxicity to BL-3 lymphocyte targets, and contai...

  15. Co-expression of ovine LPS receptor CD14 with Mannheimia haemolytica leukotoxin receptor LFA-1 or Mac-1 does not enhance leukotoxin-induced cytotoxicity

    USDA-ARS?s Scientific Manuscript database

    Leukotoxin (Lkt) and LPS are the major virulence determinants of Mannheimia haemolytica that contribute to the pathogenesis of bovine and ovine pneumonic pasteurellosis. We have previously identified bovine and ovine CD18 as the functional receptor for Lkt. LPS complexes with Lkt resulting in incre...

  16. Plane of nutrition during the preweaned period and Mannheimia haemolytica dose influence metabolic responses in post-weaned Holstein calves challenged with bovine herpesvirus-1 and Mannheimia haemolytica

    USDA-ARS?s Scientific Manuscript database

    To determine whether previous plane of milk replacer nutrition (PON) and M. haemolytica (MH) dose influences metabolic responses to a combined viral-bacterial respiratory challenge, Holstein calves (1 day of age; n=30) were assigned to treatments in a 2 x 3 factorial with preweaned PON and dose of M...

  17. Expression of a modified Mannheimia haemolytica GS60 outer membrane lipoprotein in transgenic alfalfa for the development of an edible vaccine against bovine pneumonic pasteurellosis.

    PubMed

    Lee, Raymond W H; Cornelisse, Mette; Ziauddin, Asma; Slack, Penelope J; Hodgins, Douglas C; Strommer, Judith N; Shewen, Patricia E; Lo, Reggie Y C

    2008-06-01

    The GS60 antigen is one of the protective antigens of Mannheimia haemolytica A1. GS60 contains conserved domains belonging to the LppC family of bacterial outer membrane lipoproteins. A high antibody titer to GS60 has been shown to be significantly correlated with resistance to pneumonic pasteurellosis. Calves vaccinated with a commercial vaccine (Presponse) and demonstrating protection against M. haemolytica A1 produced antibodies directed against GS60. Alfalfa was chosen as the platform for an edible vaccine. Agrobacterium tumefaciens was used to mediate the transformation of alfalfa with sequences encoding a slightly shortened derivative of the GS60 antigen (GS60(54)). Stable transgenic alfalfa lines were recovered and production of GS60(54) was examined by Western immunoblot analysis. The antigen is stable in dried transgenic plant material stored at ambient temperature for more than a year. The plant-produced GS60(54) protein was shown to be immunogenic when injected into rabbits. Feeding of the dried transgenic alfalfa expressing the GS60(54) to rabbits is capable of inducing seroconversion, suggesting that GS60(54) could be an effective oral antigen for stimulating mucosal immune responses.

  18. Differential susceptibility of bighorn sheep (Ovis Canadensis)and domestic sheep (Ovis Aries) neutrophils to Mannheimia Haemolytica Leukotoxin is not due to differential expression of cell surface CD18

    USDA-ARS?s Scientific Manuscript database

    Bighorn sheep (BHS) are more susceptible to pneumonia caused by Mannheimia haemolytica than domestic sheep (DS). Leukotoxin produced by M. haemolytica is the principal virulence factor involved in pneumonia pathogenesis. Although leukotoxin is cytolytic to all subsets of ruminant leukocytes, neutrop...

  19. An ecologic study comparing distribution of Pasteurella trehalosi and Mannheimia haemolytica between Sierra Nevada bighorn sheep, White Mountain bighorn sheep, and domestic sheep.

    PubMed

    Tomassini, Letizia; Gonzales, Ben; Weiser, Glen C; Sischo, William

    2009-10-01

    The prevalence and phenotypic variability of Pasteurella and Mannheimia isolates from Sierra Nevada bighorn sheep (Ovis canadensis sierrae), White Mountain bighorn sheep (Ovis canadensis nelsoni), and domestic sheep (Ovis aries) from California, USA, were compared. The White Mountain bighorn sheep population had a recent history of pneumonia-associated mortality, whereas the Sierra Nevada bighorn sheep population had no recent history of pneumonia-associated mortality. The domestic sheep flocks were pastured in areas geographically near both populations but were not known to have direct contact with either bighorn sheep population. Oropharyngeal swab samples were collected from healthy domestic and bighorn sheep and cultured to characterize bacterial species, hemolysis, biogroups, and biovariants. Pasteurella trehalosi and Mannheimia haemolytica were detected in all of the study populations, but the relative proportion of each bacterial species differed among sheep populations. Pasteurella trehalosi was more common than M. haemolytica in the bighorn sheep populations, whereas the opposite was true in domestic sheep. Mannheimia haemolytica was separated into 11 biogroups, and P. trehalosi was characterized into two biogroups. Biogroup distributions for M. haemolytica and P. trehalosi differed among the three populations; however, no difference was detected for the distribution of P. trehalosi biogroups between the Sierra Nevada bighorn sheep and domestic sheep. The prevalence odds ratios (pOR) for the distribution of M. haemolytica biogroups suggested little difference between White Mountain bighorn sheep and domestic sheep compared with Sierra Nevada bighorn sheep and domestic sheep, although these comparisons had relatively large confidence intervals for the point estimates. Hemolytic activity of the isolates was not different among the sheep populations for M. haemolytica but was different for P. trehalosi. No clear evidence of association was found in the

  20. Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep.

    PubMed

    Batra, Sai A; Shanthalingam, Sudarvili; Munske, Gerhard R; Raghavan, Bindu; Kugadas, Abirami; Bavanthasivam, Jegarubee; Highlander, Sarah K; Srikumaran, Subramaniam

    2015-10-01

    Mannheimia haemolytica causes pneumonia in domestic and wild ruminants. Leukotoxin (Lkt) is the most important virulence factor of the bacterium. It is encoded within the four-gene lktCABD operon: lktA encodes the structural protoxin, and lktC encodes a trans-acylase that adds fatty acid chains to internal lysine residues in the protoxin, which is then secreted from the cell by a type 1 secretion system apparatus encoded by lktB and lktD. It has been reported that LktC-mediated acylation is necessary for the biological effects of the toxin. However, an LktC mutant that we developed previously was only partially attenuated in its virulence for cattle. The objective of this study was to elucidate the role of LktC-mediated acylation in Lkt-induced cytotoxicity. We performed this study in bighorn sheep (Ovis canadensis) (BHS), since they are highly susceptible to M. haemolytica infection. The LktC mutant caused fatal pneumonia in 40% of inoculated BHS. On necropsy, a large number of necrotic polymorphonuclear leukocytes (PMNs) were observed in the lungs. Lkt from the mutant was cytotoxic to BHS PMNs in an in vitro cytotoxicity assay. Flow cytometric analysis of mutant Lkt-treated PMNs revealed the induction of necrosis. Scanning electron microscopic analysis revealed the presence of pores and blebs on mutant-Lkt-treated PMNs. Mass spectrometric analysis confirmed that the mutant secreted an unacylated Lkt. Taken together, these results suggest that acylation is not necessary for the cytotoxic activity of M. haemolytica Lkt but that it enhances the potency of the toxin. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  1. Acylation Enhances, but Is Not Required for, the Cytotoxic Activity of Mannheimia haemolytica Leukotoxin in Bighorn Sheep

    PubMed Central

    Batra, Sai A.; Shanthalingam, Sudarvili; Munske, Gerhard R.; Raghavan, Bindu; Kugadas, Abirami; Bavanthasivam, Jegarubee; Highlander, Sarah K.

    2015-01-01

    Mannheimia haemolytica causes pneumonia in domestic and wild ruminants. Leukotoxin (Lkt) is the most important virulence factor of the bacterium. It is encoded within the four-gene lktCABD operon: lktA encodes the structural protoxin, and lktC encodes a trans-acylase that adds fatty acid chains to internal lysine residues in the protoxin, which is then secreted from the cell by a type 1 secretion system apparatus encoded by lktB and lktD. It has been reported that LktC-mediated acylation is necessary for the biological effects of the toxin. However, an LktC mutant that we developed previously was only partially attenuated in its virulence for cattle. The objective of this study was to elucidate the role of LktC-mediated acylation in Lkt-induced cytotoxicity. We performed this study in bighorn sheep (Ovis canadensis) (BHS), since they are highly susceptible to M. haemolytica infection. The LktC mutant caused fatal pneumonia in 40% of inoculated BHS. On necropsy, a large number of necrotic polymorphonuclear leukocytes (PMNs) were observed in the lungs. Lkt from the mutant was cytotoxic to BHS PMNs in an in vitro cytotoxicity assay. Flow cytometric analysis of mutant Lkt-treated PMNs revealed the induction of necrosis. Scanning electron microscopic analysis revealed the presence of pores and blebs on mutant-Lkt-treated PMNs. Mass spectrometric analysis confirmed that the mutant secreted an unacylated Lkt. Taken together, these results suggest that acylation is not necessary for the cytotoxic activity of M. haemolytica Lkt but that it enhances the potency of the toxin. PMID:26216418

  2. Genomic signatures of Mannheimia haemolytica that associate with the lungs of cattle with respiratory disease, an integrative conjugative element, and antibiotic resistance genes.

    PubMed

    Clawson, Michael L; Murray, Robert W; Sweeney, Michael T; Apley, Michael D; DeDonder, Keith D; Capik, Sarah F; Larson, Robert L; Lubbers, Brian V; White, Brad J; Kalbfleisch, Theodore S; Schuller, Gennie; Dickey, Aaron M; Harhay, Gregory P; Heaton, Michael P; Chitko-McKown, Carol G; Brichta-Harhay, Dayna M; Bono, James L; Smith, Timothy P L

    2016-11-29

    Mannheimia haemolytica typically resides in cattle as a commensal member of the upper respiratory tract microbiome. However, some strains can invade their lungs and cause respiratory disease and death, including those with multi-drug resistance. A nucleotide polymorphism typing system was developed for M. haemolytica from the genome sequences of 1133 North American isolates, and used to identify genetic differences between isolates from the lungs and upper respiratory tract of cattle with and without clinical signs of respiratory disease. A total of 26,081 nucleotide polymorphisms were characterized after quality control filtering of 48,403 putative polymorphisms. Phylogenetic analyses of nucleotide polymorphism genotypes split M. haemolytica into two major genotypes (1 and 2) that each were further divided into multiple subtypes. Multiple polymorphisms were identified with alleles that tagged genotypes 1 or 2, and their respective subtypes. Only genotype 2 M. haemolytica associated with the lungs of diseased cattle and the sequence of a particular integrative and conjugative element (ICE). Additionally, isolates belonging to one subtype of genotype 2 (2b), had the majority of antibiotic resistance genes detected in this study, which were assorted into seven combinations that ranged from 1 to 12 resistance genes. Typing of diverse M. haemolytica by nucleotide polymorphism genotypes successfully identified associations with diseased cattle lungs, ICE sequence, and antibiotic resistance genes. Management of cattle by their carriage of M. haemolytica could be an effective intervention strategy to reduce the prevalence of respiratory disease and supplemental needs for antibiotic treatments in North American herds.

  3. Effects of sub-minimum inhibitory concentration antibiotic levels and temperature on growth kinetics and outer membrane protein expression in Mannheimia haemolytica and Haemophilus somnus

    PubMed Central

    2005-01-01

    Abstract The objective of this study was to determine the effects of sub-minimum inhibitory concentrations (sub-MICs) of 2 veterinary antibiotic preparations, chlortetracycline (CTC) and chlortetracycline-sulfamethazine (CTC + SMZ), on growth kinetics and outer membrane protein expression in Mannheimia haemolytica and Haemophilus somnus at normal and febrile body temperatures. Sub-minimum inhibitory concentrations of both antibiotics reduced the growth rates of M. haemolytica and H. somnus. Growth of both species was not inhibited when grown at 41°C compared to 37°C. There was no detectable consistent effect of antibiotic or temperature on outer membrane protein expression for either species. Our study indicates that sub-MIC levels of CTC and CTC + SMZ markedly impair growth of clinical M. haemolytica and H. somnus isolates, potentially allowing more effective host clearance during infection. PMID:15745216

  4. A Three-way Comparative Genomic Analysis of Mannheimia haemolytica Isolates

    SciTech Connect

    Lawrence, Paulraj; Kittichotirat, Weerayuth; McDermott, Jason E.; Bumgarner, Roger E.

    2010-10-04

    Mannhemia haemolytica is a Gram- negative bacterium and the principal etiological agent associated with bovine respiratory disease complex. They transform from a benign commensal to a deadly pathogen during stress such as viral infection and transportation to feedlots, and cause acute pleuropneumonia commonly known as shipping fever. The U.S beef industry alone loses more than one billion dollars annually to shipping fever and despite its enormous economic importance there are no specific and accurate genetic markers, which would aid in understanding M. haemolytica pathogenesis and epidemiology at molecular level and assist in devising an effective control strategy.

  5. Rapid typing of Mannheimia haemolytica major genotypes 1 and 2 using MALDI-TOF mass spectrometry.

    PubMed

    Loy, John Dustin; Clawson, Michael L

    2017-05-01

    Genotype 2M. haemolytica predominantly associate over genotype 1 with the lungs of cattle with respiratory disease and ICEs containing antimicrobial resistance genes. Distinct protein masses were detected by MALDI-TOF MS between genotype 1 and 2 strains. MALDI-TOF MS could rapidly differentiate genotype 2 strains in veterinary diagnostic laboratories.

  6. Rapid typing of Mannheimia haemolytica major genotypes 1 and 2 using MALDI-TOF mass spectrometry

    USDA-ARS?s Scientific Manuscript database

    Genotype 2 M. haemolytica predominantly associate over genotype 1 with the lungs of cattle with respiratory disease and ICEs containing antimicrobial resistance genes. Distinct protein masses were detected by MALDI-TOF MS between genotype 1 and 2 strains. MALDI-TOF MS could rapidly differentiate ge...

  7. Effect of Mannheimia haemolytica pneumonia on behavior and physiologic responses of calves during high ambient environmental temperatures.

    PubMed

    Theurer, M E; Anderson, D E; White, B J; Miesner, M D; Mosier, D A; Coetzee, J F; Lakritz, J; Amrine, D E

    2013-08-01

    The objective of this study was to determine the effect of pneumonia during conditions of high (maximum ≥ 32°C) ambient temperatures on physiological and behavioral responses of calves. Eighteen black beef heifers averaging 240 kg were blocked by BW and randomly assigned to 1 of 2 treatment groups: 1) pneumonia induced by bronchoselective endoscopic inoculation with Mannheimia haemolytica (MH; n = 10) and 2) noninoculated controls (CN; n = 8). Nasal passage and rectal temperatures were measured every 2 h for 24 h after challenge and then twice daily for 9 d. Accelerometers, pedometers, and positioning devices monitored cattle behavior within the pen for 9 d after challenge. Blood samples were collected on trial d 0, 0.5, 1, 2, 3, 7, and 9 and were analyzed to determine the concentration of substance P, cortisol, haptoglobin, and metalloproteinase. All calves in the MH group were euthanized and necropsied on trial d 9. All MH calves became clinically ill postchallenge. A treatment × time interaction (P < 0.05) was evident for nasal and rectal temperatures, behavior, weight, and blood analysis. Rectal temperatures in MH were higher (P < 0.01) than CN during the period from 6 to 24 h after challenge. Conversely, nasal passage temperatures were less in MH calves compared with CN at 12 to 22 h after challenge. Calves in MH spent less time at the grain bunk, less time at the hay feeder, and more time lying down during the early pneumonia period compared with CN calves. Also, MH calves had significantly greater concentrations of blood biomarkers of pain (substance P) on d 0.5 (P < 0.01); stress (cortisol) on d 0.5 and 1 (P < 0.01); haptoglobin on d 0.5, 1, 2, 3, 7 (P < 0.01); and metalloproteinase on d 1, 2, and 3 (P < 0.01) compared with CN calves. At necropsy, all MH calves had right cranioventral bronchopneumonia (median lung lesions = 6.8%). Mannheimia haemolytica pneumonia caused significantly more changes in behavior and increased biomarkers during high (maximum

  8. Pharmacodynamics of amoxicillin against Mannheimia haemolytica and Pasteurella multocida and pharmacokinetic/pharmacodynamic (PK/PD) correlation in sheep.

    PubMed

    Delis, G A; Koutsoviti-Papadopoulou, M; Siarkou, V I; Kounenis, G; Batzias, G C

    2010-12-01

    Silicone-made tissue cages were implanted in sheep. Blood serum (SBS) and tissue cage fluid (TCF) samples were collected after amoxicillin intravenous and intramuscular administrations, at the dose of 15 mg/kg. Amoxicillin pharmacodynamics were studied in an artificial culture medium, SBS and TCF with use of a Mannheimia haemolytica and a Pasteurella multocida strain. A concentration-independent antimicrobial activity of amoxicillin was confirmed for levels higher than 0.79-1.75×MIC. This result favored the use of the percentage of the 24 h dosing interval during which drug levels remain above MIC as the appropriate pharmacokinetic/pharmacodynamic index. The subsequent correlation revealed that intravenous administration could be considered effective against "deep" infections caused by bacteria with MICs<1 μg/mL or "shallow" infections caused by bacteria with MICs<0.1 μg/mL. Intramuscular administration could be safely considered effective against both "deep" and "shallow" infections when the MICs of the targeted pathogens are lower than 1 μg/mL.

  9. Molecular epidemiology of an outbreak of clinical mastitis in sheep caused by Mannheimia haemolytica.

    PubMed

    Omaleki, Lida; Browning, Glenn F; Allen, Joanne L; Markham, Philip F; Barber, Stuart R

    2016-08-15

    The aetiology and epidemiology of outbreaks of clinical mastitis in sheep under extensive pastoral conditions are incompletely understood. The objective of this study was to conduct a detailed investigation of a clinical mastitis outbreak that affected more than 10% of 230 at-risk ewes on a sheep and grain producing property in south east Australia during drought conditions in 2009. Milk samples were collected aseptically from all affected ewes and plated on sheep blood agar for bacterial identification. M. haemolytica was isolated from 80% of the samples that yielded cultivable microorganisms and thus was the main microorganism responsible for the outbreak. Analysis of the restriction endonuclease cleavage patterns of the isolates using pulsed field gel electrophoresis revealed some evidence of clonality, suggesting the possibility of horizontal transmission, but there was also considerable diversity between the clusters of closely related isolates. Multilocus sequence typing of the M. haemolytica isolates revealed most of the isolates belonged to ST1 with no association between the PFGE and MLST fingerprints of the isolates. Resistance to neomycin, streptomycin and sulphafurazole was detected in some of the isolates, but they were all susceptible to penicillin, ampicillin, ceftiofur, amoxycillin/clavulanic acid, ciprofloxacin, tetracycline, erythromycin and trimethoprim. This is the first published record of a comparison of the strains of M. haemolytica involved in a clinical mastitis outbreak in sheep and demonstrates the importance of this pathogen in sheep production systems, particularly during adverse climatic conditions and increased stocking rate.

  10. Differential expression of interleukin-8 by polymorphonuclear leukocytes of two closely related species, Ovis canadensis and Ovis aries, in response to Mannheimia haemolytica infection.

    PubMed

    Herndon, Caroline N; Foreyt, William J; Srikumaran, Subramaniam

    2010-08-01

    The pneumonic lesions and mortality caused by Mannheimia haemolytica in bighorn sheep (BHS; Ovis canadensis) are more severe than those in the related species, domestic sheep (DS; Ovis aries), under both natural and experimental conditions. Leukotoxin (Lkt) and lipopolysaccharide (LPS) are the most important virulence factors of this organism. One hallmark of pathogenesis of pneumonia is the influx of polymorphonuclear leukocytes (PMNs) into the lungs. Lkt-induced cytolysis of PMNs results in the release of cytotoxic compounds capable of damaging lung tissue. Interleukin-8 (IL-8) is a potent PMN chemoattractant. The objective of the present study was to determine if there is differential expression of IL-8 by the macrophages and PMNs of BHS and DS in response to M. haemolytica. Macrophages and PMNs of BHS and DS were stimulated with heat-killed M. haemolytica or LPS. IL-8 expression by the cells was measured by enzyme-linked immunosorbent assays and real-time reverse transcription-PCR (RT-PCR). The PMNs of BHS expressed severalfold higher levels of IL-8 than those of DS upon stimulation. Lesional lung tissue of M. haemolytica-infected BHS contained significantly higher levels of IL-8 than nonlesional tissue. The bronchoalveolar lavage (BAL) fluid of infected BHS also contained higher levels of IL-8 than that of infected DS. Depletion of IL-8 reduced migration of PMNs toward BAL fluid by approximately 50%, indicating that IL-8 is integral to PMN recruitment to the lung during M. haemolytica infection. Excessive production of IL-8, enhanced recruitment of PMNs, and PMN lysis by Lkt are likely responsible for the severity of the lung lesions in M. haemolytica-infected BHS.

  11. Comparison of passively transferred antibodies in bighorn and domestic lambs reveals one factor in differential susceptibility of these species to Mannheimia haemolytica-induced pneumonia.

    PubMed

    Herndon, Caroline N; Shanthalingam, Sudarvili; Knowles, Donald P; Call, Douglas R; Srikumaran, Subramaniam

    2011-07-01

    Mannheimia haemolytica consistently causes fatal bronchopneumonia in bighorn sheep (BHS; Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related species Ovis aries (domestic sheep [DS]). In BHS herds affected by pneumonia, lamb recruitment is severely impaired for years subsequent to an outbreak. We hypothesized that a lack of maternally derived antibodies (Abs) against M. haemolytica provides an immunologic basis for enhanced susceptibility of BH lambs to population-limiting pneumonia. Therefore, the objective of this study was to determine the titers of Abs directed against M. haemolytica in the sera of BH and domestic lambs at birth through 12 weeks of age. Results revealed that BH lambs had approximately 18-fold lower titers of Ab against surface antigens of M. haemolytica and approximately 20-fold lower titers of leukotoxin-neutralizing Abs than domestic lambs. The titers of leukotoxin-neutralizing Abs in the serum and colostrum samples of BH ewes were approximately 157- and 50-fold lower than those for domestic ewes, respectively. Comparatively, the higher titers of parainfluenza 3 virus-neutralizing Abs in the BH lambs ruled out the possibility that these BHS had an impaired ability to passively transfer Abs to their lambs. These results suggest that lower levels of leukotoxin-neutralizing Abs in the sera of BH ewes, and resultant low Ab titers in their lambs, may be a critical factor in the poor lamb recruitment in herds affected by pneumonia.

  12. Transmission of Mannheimia haemolytica from domestic sheep (Ovis aries) to bighorn sheep (Ovis canadensis): unequivocal demonstration with green fluorescent protein-tagged organisms.

    PubMed

    Lawrence, Paulraj K; Shanthalingam, Sudarvili; Dassanayake, Rohana P; Subramaniam, Renuka; Herndon, Caroline N; Knowles, Donald P; Rurangirwa, Fred R; Foreyt, William J; Wayman, Gary; Marciel, Ann Marie; Highlander, Sarah K; Srikumaran, Subramaniam

    2010-07-01

    Previous studies demonstrated that bighorn sheep (Ovis canadensis) died of pneumonia when commingled with domestic sheep (Ovis aries) but did not conclusively prove that the responsible pathogens were transmitted from domestic to bighorn sheep. The objective of this study was to determine, unambiguously, whether Mannheimia haemolytica can be transmitted from domestic to bighorn sheep when they commingle. Four isolates of M. haemolytica were obtained from the pharynx of two of four domestic sheep and tagged with a plasmid carrying the genes for green fluorescent protein (GFP) and ampicillin resistance (AP(R)). Four domestic sheep, colonized with the tagged bacteria, were kept about 10 m apart from four bighorn sheep for 1 mo with no clinical signs of pneumonia observed in the bighorn sheep during that period. The domestic and bighorn sheep were then allowed to have fence-line contact for 2 mo. During that period, three bighorn sheep acquired the tagged bacteria from the domestic sheep. At the end of the 2 mo of fence-line contact, the animals were allowed to commingle. All four bighorn sheep died 2 days to 9 days following commingling. The lungs from all four bighorn sheep showed gross and histopathologic lesions characteristic of M. haemolytica pneumonia. Tagged M. haemolytica were isolated from all four bighorn sheep, as confirmed by growth in ampicillin-containing culture medium, PCR-amplification of genes encoding GFP and Ap(R), and immunofluorescent staining of GFP. These results unequivocally demonstrate transmission of M. haemolytica from domestic to bighorn sheep, resulting in pneumonia and death of bighorn sheep.

  13. Pulmonary lesions and clinical disease response to Mannheimia haemolytica challenge 10 days following administration of tildipirosin or tulathromycin.

    PubMed

    Amrine, D E; White, B J; Larson, R L; Mosier, D A

    2014-01-01

    This clinical trial evaluated the impact of metaphylactic antimicrobial administration 10 d before experimental inoculation with Mannheimia haemolytica (MH) to mitigate pulmonary lesions. Thirty-three crossbreed heifers were procured as a single group and were randomly allocated to 1 of 3 blocks and to treatment, tildipirosin (ZUP; 4 mg/kg) or tulathromycin (DRX; 2.5 mg/kg) or saline (SAL; 1 mL/45.5 kg), within block on arrival at Kansas State University. All trial procedures were staggered by 7-d intervals for each block, resulting in all animals within a block receiving treatment, challenge, and necropsy on the same dates. Heifers within each block received an endoscopic MH challenge 10 d following treatment administration (d 0) and were housed in individual indoor stalls for 3 d postchallenge. Clinical illness scores (CIS), respiration quality scores, appetite scores, and injection site reactions were recorded on all animals from d 0 through d 13. Rectal temperatures were measured once daily on all animals from d 8 through d 13. Heifers were necropsied, and lung lesions were evaluated on d 13. Lung lesion data were evaluated using nonparametric methods (Kruskall-Wallis), and standard least squares models were used to evaluate the remaining variables. The pulmonary lesion scores (percentage of affected lung) ranged from 3.3% to 39.8% for all heifers with 92% (11/12) of ZUP-treated heifers having <10% lesions. Tildipirosin-treated heifers had lower (P < 0.05) lung lesion scores when compared with DRX- and SAL-treated heifers. Lung weight expressed as a percentage of BW was lower (P < 0.05) in ZUP heifers compared to DRX- and SAL-treated heifers. The probability of receiving abnormal CIS, appetite scores, and respiratory scores was lower (P < 0.05) in ZUP-treated heifers compared to DRX- and SAL-treated animals. This study showed that heifers treated with tildipirosin 10 d before MH challenge have less pulmonary damage and fewer clinical signs of illness compared

  14. Rumen temperature change monitored with remote rumen temperature boluses after challenges with bovine viral diarrhea virus and Mannheimia haemolytica.

    PubMed

    Rose-Dye, T K; Burciaga-Robles, L O; Krehbiel, C R; Step, D L; Fulton, R W; Confer, A W; Richards, C J

    2011-04-01

    Remote rumen temperature monitoring is a potential method for early disease detection in beef cattle. This experiment was conducted to determine if remotely monitored rumen temperature boluses could detect a temperature change in steers exposed to bovine viral diarrhea virus (BVDV) and challenged with a common bovine respiratory disease pathogen, Mannheimia haemolytica (MH). Twenty-four Angus crossbred steers (BW = 313 ± 31 kg) were allotted to 1 of 4 treatments: 1) no challenge (control); 2) challenge by a 72-h exposure to 2 steers persistently infected with BVDV; 3) bacterial challenge with MH; and 4) viral challenge by a 72-h exposure to 2 steers persistently infected with BVDV followed by bacterial challenge with MH (BVDV + MH). Remotely monitored rumen temperature boluses programmed to transmit temperature every minute were placed in the rumen before the time of exposure to steers persistently infected with BVDV. Rectal temperatures were taken before MH challenge (0) and at 2, 4, 6, 12, 18, 24, 36, 48, 72, and 96 h after MH challenge. Rumen temperatures were recorded 3 d before (-72 h; period of BVDV exposure) through 14 d after (336 h) MH challenge. Rumen temperatures were analyzed as a randomized complete block design with a 2 × 2 factorial arrangement of treatments and a first-order autoregressive covariance structure for repeated measures. A treatment × day interaction was observed for average daily rumen temperature (P < 0.01). A treatment difference (P < 0.01) was observed on d 0, when MH-challenged steers had greater rumen temperatures than steers not challenged with MH. There was no BVDV × day interaction (P > 0.01). Rumen temperatures averaged every 2 h resulted in a BVDV × hour interaction (P < 0.01) and an MH × hour interaction (P < 0.01). The BVDV × hour differences occurred at h -18 to -14, 40 to 46, 110, 122, and 144 to 146 (P < 0.01). The MH × hour difference occurred at h 4 to 24 (P < 0.01). Maximum rumen temperature was increased (P

  15. Comparison of Passively Transferred Antibodies in Bighorn and Domestic Lambs Reveals One Factor in Differential Susceptibility of These Species to Mannheimia haemolytica-Induced Pneumonia ▿

    PubMed Central

    Herndon, Caroline N.; Shanthalingam, Sudarvili; Knowles, Donald P.; Call, Douglas R.; Srikumaran, Subramaniam

    2011-01-01

    Mannheimia haemolytica consistently causes fatal bronchopneumonia in bighorn sheep (BHS; Ovis canadensis) under natural and experimental conditions. Leukotoxin is the primary virulence factor of this organism. BHS are more susceptible to developing fatal pneumonia than the related species Ovis aries (domestic sheep [DS]). In BHS herds affected by pneumonia, lamb recruitment is severely impaired for years subsequent to an outbreak. We hypothesized that a lack of maternally derived antibodies (Abs) against M. haemolytica provides an immunologic basis for enhanced susceptibility of BH lambs to population-limiting pneumonia. Therefore, the objective of this study was to determine the titers of Abs directed against M. haemolytica in the sera of BH and domestic lambs at birth through 12 weeks of age. Results revealed that BH lambs had approximately 18-fold lower titers of Ab against surface antigens of M. haemolytica and approximately 20-fold lower titers of leukotoxin-neutralizing Abs than domestic lambs. The titers of leukotoxin-neutralizing Abs in the serum and colostrum samples of BH ewes were approximately 157- and 50-fold lower than those for domestic ewes, respectively. Comparatively, the higher titers of parainfluenza 3 virus-neutralizing Abs in the BH lambs ruled out the possibility that these BHS had an impaired ability to passively transfer Abs to their lambs. These results suggest that lower levels of leukotoxin-neutralizing Abs in the sera of BH ewes, and resultant low Ab titers in their lambs, may be a critical factor in the poor lamb recruitment in herds affected by pneumonia. PMID:21613459

  16. Transfection of non-susceptible cells with Ovis aries recombinant lymphocyte function-associated antigen 1 renders susceptibility to Mannheimia haemolytica leukotoxin.

    PubMed

    Lawrence, Paulraj K; Dassanayake, Rohana P; Knowles, Donald P; Srikumaran, Subramaniam

    2007-11-15

    Mannheimia haemolytica is an important etiological agent of pneumonia in domestic sheep (DS, Ovis aries). Leukotoxin (Lkt) produced by this organism is the principal virulence factor responsible for the acute inflammation and lung injury characteristic of M. haemolytica caused disease. Previously, we have shown that the leukocyte-specific integrins, beta(2) integrins, serve as the receptor for Lkt. Although it is certain that CD18, the beta subunit of beta(2) integrins, mediates Lkt-induced cytolysis of leukocytes, it is not clear whether CD18 of all three beta(2) integrins, LFA-1, Mac-1 and CR4, mediates Lkt-induced cytolysis of DS leukocytes. Since polymorphonuclear leukocytes, which express all three beta(2) integrins, are the leukocyte subset that is most susceptible to Lkt, we hypothesized that all three beta(2) integrins serve as the receptor for Lkt. The objective of this study was to determine whether DS LFA-1 serves as a receptor for M. haemolytica Lkt. We cloned the cDNA for DS CD11a, the alpha subunit of LFA-1, and co-transfected it along with the previously cloned cDNA for DS CD18, into a Lkt-non-suceptible cell line. Transfectants stably expressing DS LFA-1 were bound by Lkt. More importantly, Lkt lysed the DS LFA-1 transfectants in a concentration-dependent manner. Pre-incubation of Lkt with a Lkt-neutralizing monoclonal antibody (MAb), or pre-incubation of transfectants with MAbs specific for DS CD11a or CD18, inhibited Lkt-induced cytolysis of the transfectants. Exposure of LFA-1 transfectants to low concentrations of Lkt resulted in elevation of intracellular [Ca(2+)](i). Taken together, these results indicate that DS LFA-1 serves as a receptor for M. haemolytica Lkt.

  17. Comparative minimum inhibitory and mutant prevention drug concentrations of enrofloxacin, ceftiofur, florfenicol, tilmicosin and tulathromycin against bovine clinical isolates of Mannheimia haemolytica.

    PubMed

    Blondeau, J M; Borsos, S; Blondeau, L D; Blondeau, B J J; Hesje, C E

    2012-11-09

    Mannheimia haemolytica is the most prevalent cause of bovine respiratory disease (BRD) and this disease accounts for 75% of morbidity, 50-70% of feedlot deaths and is estimated to cost up to $1 billion dollars annually in the USA. Antimicrobial therapy is essential for reducing morbidity, mortality and impacting on the financial burden of this disease. Due to the concern of increasing antimicrobial resistance, investigation of antibacterial agents for their potential for selecting for resistance is of paramount importance. A novel in vitro measurement called the mutant prevention concentration (MPC) defines the antimicrobial drug concentration necessary to block the growth of the least susceptible cells present in high density (≥10(7) colony forming units/ml) bacterial populations such as those seen in acute infection. We compared the minimum inhibitory concentration (MIC) and MPC values for 5 antimicrobial agents (ceftiofur, enrofloxacin, florfenicol, tilmicosin, tulathromycin) against 285 M. haemolytica clinical isolates. The MIC(90)/MPC(90) values for each agent respectively were as follows: 0.016/2, 0.125/1, 2/≥16, 8/≥32, 2/8. Dosing to achieve MPC concentrations (where possible) may serve to reduce the selection of bacterial subpopulations with reduced antimicrobial susceptibility. The rank order of potency based on MIC(90) values was ceftiofur > enrofloxacin > florfenicol = tulathromycin > tilmicosin. The rank order of potency based on MPC(90) values was enrofloxacin > ceftiofur > tulathromycin > florfenicol ≥ tilmicosin.

  18. Differential Susceptibility of Bighorn Sheep (Ovis canadensis) and Domestic Sheep (Ovis aries) Neutrophils to Mannheimia haemolytica Leukotoxin is not due to Differential Expression of Cell Surface CD18.

    PubMed

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Liu, Weiguo; Casas, Eduardo; Srikumaran, Subramaniam

    2017-07-01

    Bighornsheep ( Ovis canadensis ) are more susceptible to pneumonia caused by Mannheimia haemolytica than are domestic sheep ( Ovis aries ). Leukotoxin produced by M. haemolytica is the principal virulence factor involved in pneumonia pathogenesis. Although leukotoxin is cytolytic to all subsets of ruminant leukocytes, neutrophils are the most susceptible subset. Bighorn sheep neutrophils are four- to eightfold more susceptible to leukotoxin-induced cytolysis than are domestic sheep neutrophils. We hypothesized that the higher susceptibility of bighorn sheep neutrophils, in comparison to domestic sheep neutrophils, is due to higher expression of CD18, the receptor for leukotoxin on leukocytes. Our objective was to quantify CD18 expression on neutrophils of bighorn sheep and domestic sheep. Cell-surface CD18 expression on bighorn sheep and domestic sheep neutrophils was measured as antibody binding capacity of cells by flow cytometric analysis with two fluorochrome-conjugated anti-CD18 monoclonal antibodies (BAQ30A and HUH82A) and microspheres. Contrary to our expectations, CD18 expression was higher (P<0.0001) with monoclonal antibody BAQ30A and was higher (P<0.0002) as well with monoclonal antibody HUH80A on domestic sheep neutrophils in comparison to bighorn sheep neutrophils. These findings suggest that the higher in vitro susceptibility to leukotoxin of bighorn sheep neutrophils compared to domestic sheep neutrophils is not due to higher expression of the leukotoxin receptor CD18 on bighorn sheep neutrophils.

  19. Serial evaluation of physiologic, pathological, and behavioral changes related to disease progression of experimentally induced Mannheimia haemolytica pneumonia in postweaned calves.

    PubMed

    Hanzlicek, Gregg A; White, Brad J; Mosier, Derek; Renter, David G; Anderson, David E

    2010-03-01

    To determine the usefulness of physiologic, behavioral, and pathological changes as objective indicators of early respiratory disease in calves with Mannheimia haemolytica pneumonia. 14 crossbred beef steers. Disease was experimentally induced in healthy calves through endoscopic pulmonary inoculation of M haemolytica. Calves were necropsied on days 1, 2, 3, 5, 7, and 9 after inoculation. Physical examination variables (rectal temperature, heart rate, and respiration characteristics), clinical illness score, and degree of activity were assessed 3 times daily beginning 4 days prior to inoculation and continuing throughout the study. Twice before inoculation and on days 1, 2, 3, 5, 7, and 9, arterial blood gas measurements, serum biochemical analyses, and CBCs were performed. Pedometers and accelerometers were used to monitor cattle behavior and activity throughout the trial. All calves became clinically ill after inoculation and had gross and histopathologic signs of bronchopneumonia. No variable was a reliable indicator of disease progression as judged by percentage of pulmonary involvement. However, activity as measured by total steps taken in a 24-hour period was lower after versus before disease induction. This single-pathogen challenge model successfully yielded clinical signs and pathological effects consistent with naturally acquired respiratory disease. Routine laboratory variables and subjective measures were not reliable indicators of lung involvement or the progression of pneumonia. However, activity, objectively measured with pedometers and accelerometers, appeared to be a promising indicator for early recognition of bovine respiratory disease.

  20. Bovine Gamma Delta T Cells Contribute to Exacerbated IL-17 Production in Response to Co-Infection with Bovine RSV and Mannheimia haemolytica

    PubMed Central

    McGill, Jodi L.; Rusk, Rachel A.; Guerra-Maupome, Mariana; Briggs, Robert E.; Sacco, Randy E.

    2016-01-01

    Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovine RSV (BRSV) is genetically closely related to HRSV and is a leading cause of severe respiratory infections in young cattle. While BRSV infection in the calf parallels many aspects of human infection with HRSV, IL-17 and Th17 responses have not been studied in the bovine. Here we demonstrate that calves infected with BRSV express significant levels of IL-17, IL-21 and IL-22; and both CD4 T cells and γδ T cells contribute to this response. In addition to causing significant morbidity from uncomplicated infections, BRSV infection also contributes to the development of bovine respiratory disease complex (BRDC), a leading cause of morbidity in both beef and dairy cattle. BRDC is caused by a primary viral infection, followed by secondary bacterial pneumonia by pathogens such as Mannheimia haemolytica. Here, we demonstrate that in vivo infection with M. haemolytica results in increased expression of IL-17, IL-21 and IL-22. We have also developed an in vitro model of BRDC and show that co-infection of PBMC with BRSV followed by M. haemolytica leads to significantly exacerbated IL-17 production, which is primarily mediated by IL-17-producing γδ T cells. Together, our results demonstrate that calves, like humans, mount a robust IL-17 response during RSV infection; and suggest a previously unrecognized role for IL-17 and γδ T cells in the pathogenesis of BRDC. PMID:26942409

  1. Plane of nutrition during the preweaned period and Mannheimia haemolytica dose influences inflammatory responses to a combined bovine herpesvirus-1 and Mannheimia haemolytica challenge in post-weaned Holstein calves

    USDA-ARS?s Scientific Manuscript database

    To determine whether previous plane of milk replacer nutrition (PON) and M. haemolytica (MH) dose influences inflammatory responses to a combined viral-bacterial respiratory challenge, Holstein calves (1 day of age; n=30) were assigned to treatments in a 2 x 3 factorial with preweaned PON and dose o...

  2. Pharmacokinetic/pharmacodynamic integration and modelling of amoxicillin for the calf pathogens Mannheimia haemolytica and Pasteurella multocida.

    PubMed

    Lees, P; Pelligand, L; Illambas, J; Potter, T; Lacroix, M; Rycroft, A; Toutain, P-L

    2015-10-01

    The antimicrobial properties of amoxicillin were determined for the bovine respiratory tract pathogens, Mannheima haemolytica and Pasteurella multocida. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill curves were established. Pharmacokinetic (PK)/pharmacodynamic (PD) modelling of the time-kill data, based on the sigmoidal Emax equation, generated parameters for three levels of efficacy, namely bacteriostatic, bactericidal (3log10 reduction) and 4log10 reduction in bacterial counts. For these levels, mean AUC(0-24 h) /MIC serum values for M. haemolytica were 29.1, 57.3 and 71.5 h, respectively, and corresponding values for P. multocida were 28.1, 44.9 and 59.5 h. Amoxicillin PK was determined in calf serum, inflamed (exudate) and noninflamed (transudate) tissue cage fluids, after intramuscular administration of a depot formulation at a dosage of 15 mg/kg. Mean residence times were 16.5 (serum), 29.6 (exudate) and 29.0 h (transudate). Based on serum MICs, integration of in vivo PK and in vitro PD data established maximum concentration (Cmax )/MIC ratios of 13.9:1 and 25.2:1, area under concentration-time curve (AUC0-∞ )/MIC ratios of 179 and 325 h and T>MIC of 40.3 and 57.6 h for P. multocida and M. haemolytica, respectively. Monte Carlo simulations for a 90% target attainment rate predicted single dose to achieve bacteriostatic and bactericidal actions over 48 h of 17.7 and 28.3 mg/kg (M. haemolytica) and 17.7 and 34.9 mg/kg (P. multocida).

  3. Distribution of ceftiofur into Mannheimia haemolytica-infected tissue chambers and lung after subcutaneous administration of ceftiofur crystalline free acid sterile suspension.

    PubMed

    Washburn, K; Johnson, R; Clarke, C; Anderson, K

    2010-04-01

    The objective of this study was to evaluate the penetration of ceftiofur- and desfuroylceftiofur-related metabolites (DCA) into sterile and infected tissue chambers, lung tissue and disposition of DCA in plasma across four different sacrifice days postdosing. Twelve healthy calves were utilized following implantation with tissue chambers in the paralumbar fossa. Tissue chambers in each calf were randomly inoculated with either Mannheimia haemolytica or sterile PBS. All calves were dosed with ceftiofur crystalline free acid sterile suspension (CCFA-SS) subcutaneously in the ear pinna. Calves were randomly assigned to 4 groups of 3 to be sacrificed on days 3, 5, 7 and 9 postdosing. Prior to euthanasia, plasma and tissue chamber fluid were collected, and immediately following euthanasia, lung tissue samples were obtained from four different anatomical sites DCA concentration analysis. Results of our study found that, in general, DCA concentrations followed a rank order of plasma > infected tissue chamber fluid > noninfected tissue chamber fluid > lung tissue. Data also indicated DCA concentrations remained above the therapeutic threshold of 0.2 microg/mL for plasma and chamber fluid and 0.2 microg/g for lung tissue for at least 7 days post-treatment.

  4. Bivalent vaccination against pneumonic pasteurellosis in domestic sheep and goats with modified-live in-frame lktA deletion mutants of Mannheimia haemolytica.

    PubMed

    Briggs, Robert E; Hauglund, Melissa J; Maheswaran, Samuel K; Tatum, Fred M

    2013-11-01

    A temperature-sensitive shuttle vector, pBB80C, was utilized to generate in-frame deletion mutants of the leukotoxin structural gene (lktA) of Mannheimia haemolytica serotypes 1, 2, 5, 6, 7, 8, 9, and 12. Culture supernatants from the mutants contained a truncated protein with an approximate molecular weight of 66 kDa which was reactive to anti-leukotoxin monoclonal antibody. No protein reactive to anti-LktA monoclonal antibody was detected at the molecular weight 100-105 kDa of native LktA. Sheep and goats vaccinated intramuscularly with a mixture of serotypes 5 and 6 mutants were resistant to virulent challenge with a mixture of the wild-type parent strains. These vaccinates responded serologically to both vaccine serotypes and exhibited markedly-reduced lung lesion volume and pulmonary infectious load compared to control animals. Control animals yielded a mixture of serotypes from lung lobes, but the proportion even within an individual animal varied widely from 95% serotype 5-95% serotype 6. Cultures recovered from liver were homogeneous, but two animals yielded serotype 5 and the other two yielded serotype 6 in pure culture.

  5. Effect of Mannheimia (Pasteurella) haemolytica infection on acute-phase proteins and some mineral levels in colostrum-breast milk-fed or colostrum-breast milk-deprived sheep.

    PubMed

    Ulutas, P A; Ozpinar, A

    2006-07-01

    The aim of this study was to investigate the levels of acute-phase proteins and minerals as indicators for the reactivity in 1-year-old sheep. A total of 26 Chios breed sheep were fed colostrum-breast milk (control, n = 15)or were deprived afterseparation from their mother immediately after birth(experimental, n = 11). Mannheimia (Pasteurella) haemolytica serotype A1 was inoculated intratracheally and blood samples were taken in vacuumed sera on days 0, 1, 4, 7, 10, 13, 16, 19 and 22. Antibiotic treatment was initiated after blood sampling on day 22, and blood samples were taken on days 1, 4 and 7 after the treatment. The levels of C-reactive protein (CRP), haptoglobin, ceruloplasmin, fibrinogen, zinc, iron and calcium, which are the indicators of immune function and infectious diseases were analysed. No significant difference between the control and trial groups before and after the infection was determined. However, serum CRP, haptoglobin, ceruloplasmin and fibrinogen levels were increased in the course of the infection. These levels were restored to normal following treatment.

  6. Efficacy of recombinant leukotoxin in protection against pneumonic challenge with live Pasteurella haemolytica A1.

    PubMed Central

    Conlon, J A; Shewen, P E; Lo, R Y

    1991-01-01

    The recombinant leukotoxin (rLKT) of the bacterium Pasteurella haemolytica A1 was examined for its ability to protect cattle from experimental challenge with logarithmic-phase P. haemolytica. Six different vaccines were utilized in the experiment: P. haemolytica culture supernatant, P. haemolytica culture supernatant enriched with rLKT, rLKT alone, P. haemolytica culture supernatant enriched with Escherichia coli supernatant not containing LKT, E. coli supernatant alone, and phosphate-buffered saline. rLKT alone showed no protective capacity against development of clinical signs of respiratory disease or against development of postmortem lung lesions after experimental challenge. It was, however, shown to enhance the efficacy of the culture supernatant vaccine and decrease clinical signs and pneumonic lesions. The complexity of protective immunity in this disease is emphasized in this study, and, although LKT is an important virulence factor of the organism, an immune response to LKT alone does not protect animals against disease. PMID:1987075

  7. In vivo production of neuraminidase by Pasteurella haemolytica A1 in goats after transthoracic challenge.

    PubMed Central

    Straus, D C; Purdy, C W

    1994-01-01

    Nine goats were injected transthoracically with Pasteurella haemolytica A1 to determine if an extracellular bacterial enzyme, neuraminidase, was produced in vivo during infection with this organism. The principal group of goats (n = 9) each received 1 ml of 7.25 x 10(5) live P. haemolytica A1 cells in polyacrylate beads transthoracically in the left lung on days 0 and 21. Six goats were used as negative controls and received 0.3 g of polyacrylate beads subcutaneously in the right flank on days 0 and 21. Serum was obtained from all animals on days -4, 3, 7, 14, 21, 24, and 32. Preimmune serum from all animals showed no detectable antibody to P. haemolytica A1 neuraminidase in an enzyme neutralization assay. None of the sera from the negative control animals possessed a significant antibody concentration in response to the P. haemolytica A1 neuraminidase. On day 32, serum samples from the nine infected animals possessed enzyme neutralizing activity that ranged from 62% to 100%. Anti-neuraminidase antibody could be detected as early as day 14 by the enzyme neutralization assay. These data demonstrate that the enzyme neuraminidase is produced in vivo during an active P. haemolytica A1 lobar infection. PMID:7927740

  8. Cloning of a serotype-specific antigen from Pasteurella haemolytica A1.

    PubMed Central

    Gonzalez-Rayos, C; Lo, R Y; Shewen, P E; Beveridge, T J

    1986-01-01

    Recombinant plasmids coding for a soluble (or surface) antigen of Pasteurella haemolytica A1 were identified. Two plasmids, both containing the same 5.4 kilobase pairs of insert DNA, were recovered independently by screening a clone band of P. haemolytica A1 genomic DNA in Escherichia coli for the expression of P. haemolytica A1 soluble antigens (R. Y. C. Lo and L.A. Cameron, Can. J. Biochem. Cell Biol. 64:73-76, 1986). E. coli cells carrying the plasmids were found to be agglutinated by an antiserum raised against the P. haemolytica A1 soluble antigens. Analysis of the E. coli clones by electron microscopy revealed patches of amorphous material on the surface of the cells which were not present on the controls. Further characterization with protein A-colloidal gold labeled both these patches and the outer membranes of these cloned cells pretreated with the specific antiserum. These results indicated that the cloned antigen was expressed on the surface of the E. coli cells. The cloned antigen was found to be specific for serotype 1 when tested by slide agglutination against a collection of P. haemolytica typing antisera. Southern blot hybridization, using the cloned DNA as a probe, labeled the genomic DNA from P. haemolytica serotype 1 as well as the cross-agglutinating serotypes 2 and 7, but not DNA from the non-cross-agglutinating serotypes 3 and 4 and Pasteurella multocida. These results demonstrated that serotype specificity could be attributed to the particular antigenic determinants in the genome of the organism. Images PMID:3527985

  9. Penetration of ceftiofur into sterile vs. Mannheimia haemolytica-infected tissue chambers in beef calves after subcutaneous administration of ceftiofur crystalline free acid sterile suspension in the ear pinna.

    PubMed

    Washburn, K; Johnson, R; Clarke, C R; Anderson, K; Lucas, M; Bryson, W; Robinson, J; Dame, K; Hubbard, V; Callahan, K; Robb, E

    2005-06-01

    The effect of Mannheimia haemolytica infection on the penetration of ceftiofur and desfuroylceftiofur metabolites into tissue chambers was studied in cattle after subcutaneous administration of ceftiofur crystalline free acid sterile suspension (CCFA-SS). Four tissue chambers were implanted subcutaneously in each of 12 calves. Approximately 45 days after implantation, two chambers were inoculated with M. haemolytica (10(6) colony-forming units per chamber) while the remaining two chambers were inoculated with sterile phosphate-buffered saline. Twenty-four hours after inoculation, CCFA-SS was administered subcutaneously in the middle third of the caudal ear pinna of each calf. Chamber fluid and blood samples were collected at predetermined times for 10 days following dosing and analyzed for ceftiofur and desfuroylceftiofur metabolites by high-performance liquid chromatography. Concentrations of ceftiofur and desfuroylceftiofur metabolites in plasma and tissue chamber fluid remained above a threshold of 0.2 microg/mL for at least 8 days. Infected tissue chamber fluid concentrations of ceftiofur and desfuroylceftiofur metabolites were significantly higher than those in non-infected tissue chamber fluid, which correlated with significantly higher total protein concentration in infected tissue chambers. These results indicate that single subcutaneous administration of CCFA-SS at 6.6 mg/kg can be expected to provide effective therapy of susceptible bacterial infections for a period of at least 1 week.

  10. Molecular studies of Ssa1, a serotype-specific antigen of Pasteurella haemolytica A1.

    PubMed Central

    Lo, R Y; Strathdee, C A; Shewen, P E; Cooney, B J

    1991-01-01

    A serotype-specific antigen of Pasteurella haemolytica A1 encoded on the recombinant plasmid pSSA1 is characterized. Nucleotide sequence analysis of the insert DNA in pSSA1 identified the gene ssaI, which codes for a protein of approximately 100 kDa. In vivo labeling of pSSA1-encoded protein in Escherichia coli maxicells showed the expression of a 100-kDa protein from the insert DNA on the recombinant plasmid. Northern blot and primer extension analyses were used to identify the mRNA transcript in P. haemolytica A1 and the putative promoter of ssaI. The antigen (designated Ssa1) could be localized to the outer membrane of P. haemolytica A1 and E. coli clones carrying pSSA1. A rabbit serum against Ssa1 was produced by using whole cells of E. coli expressing Ssa1 on the surface as the immunogen, demonstrating that Ssa1 is immunogenic in rabbits. The results from colony immunoblot analysis with calf serum from animals that were resistant to P. haemolytica A1-induced pneumonia suggest indirectly that Ssa1 is also immunogenic in the animals. Images PMID:1840576

  11. Sialoglycoprotease of Pasteurella haemolytica A1: detection of antisialoglycoprotease antibodies in sera of calves.

    PubMed Central

    Lee, C W; Shewen, P E; Cladman, W M; Conlon, J A; Mellors, A; Lo, R Y

    1994-01-01

    Log phase culture supernate from Pasteurella haemolytica biotype A, serotype 1 contains a proteolytic enzyme specific for O-sialoglycoproteins. Using two methods, Western immunoblotting and enzyme neutralization assay, it was demonstrated that certain bovine sera from two previous P. haemolytica A1 vaccination and challenge trials contained antibodies (Ab) (isotypes IgG1 and IgG2 on Western immunoblot) to the sialoglycoprotease (Gcp). In these trials, selected calves were vaccinated twice with either the commercial culture supernate vaccine Presponse or given phosphate-buffered saline (PBS). One trial was conducted during spring, P. haem XIX, and the other during the winter, P. haem XXI. Although there was no clear evidence for induction of anti-Gcp in response to vaccination, several calves seroconverted following intrapulmonary challenge with live P. haemolytica A1. This is the first report of anti-Gcp Ab in bovine sera. The results indicated that the Gcp is immunogenic and that the bacterium produces the enzyme in vivo. Further, animals with an anti-Gcp response had less pneumonia at necropsy, suggesting the Gcp may induce protective immunity. Images Fig. 1. Fig. 2. PMID:8004547

  12. Neuraminidase production by a Pasteurella haemolytica A1 strain associated with bovine pneumonia.

    PubMed Central

    Straus, D C; Unbehagen, P J; Purdy, C W

    1993-01-01

    The properties of an extracellular neuroaminidase produced by a Pasteurella haemolytica A1 strain (isolated from a case of bovine pneumonia) during growth in a defined medium were examined in this investigation. This enzyme, isolated from concentrated culture supernatants of P. haemolytica A1, was active against N-acetylneuramin lactose, human alpha 1-acid glycoprotein, fetuin, and bovine submaxillary mucin. Neuraminidase production paralleled bacterial growth in a defined medium and was maximal in the stationary phase of growth. The enzyme was purified to homogeneity by a combination of salt fractionation, ion-exchange chromatography on DEAE-Sephacel, and gel filtration on Sephadex G-200. These procedures yielded an enzyme preparation that possessed a specific activity of 100.62 mumol of sialic acid released per min per mg of protein against human alpha 1-acid glycoprotein. The Km value for this enzyme with human alpha 1-acid glycoprotein as the substrate was 1.1 mg/ml, and the enzyme possessed a pH optimum of 6.5. The P. haemolytica A1 neuraminidase had a molecular weight of approximately 150,000 as estimated by gel filtration and approximately 170,000 when analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. The enzyme was stable at 4 degrees C for 3 h. At 37 degrees C for 3 h, 25% of enzymatic activity was lost. Approximately 55% of the enzyme activity was lost within 30 min at 50 degrees C, with greater than 70% of the enzyme activity being destroyed within 10 min at temperatures of > or = 65 degrees C. Images PMID:8418046

  13. Cloning and expression of the leukotoxin gene of Pasteurella haemolytica A1 in Escherichia coli K-12.

    PubMed Central

    Lo, R Y; Shewen, P E; Strathdee, C A; Greer, C N

    1985-01-01

    A clone bank of Pasteurella haemolytica A1 was constructed by partial digestion of the genomic DNA with Sau3A and ligation of 5- to 10-kilobase-pair fragments into the BamHI site of the plasmid vector pBR322. After transformation into Escherichia coli K-12, a total of 4 X 10(3) recombinant clones was obtained. These were screened for the production of P. haemolytica soluble antigens by a colony enzyme-linked immunosorbent assay blot method with a rabbit antiserum raised against the soluble antigens. The clones producing P. haemolytica soluble antigens were then analyzed for the production of the leukotoxin by a cytotoxicity assay with cells from a bovine leukemia-derived B-lymphocyte cell line as the target cells. Positive clones were identified, and subsequent restriction analysis of the recombinant plasmids showed that the same 6.3 kilobase pairs of insert DNA was cloned in either of the two orientations into the plasmid vector pBR322. One of the clones was selected for further characterization of the leukotoxin as produced in E. coli. Tests for heat lability and target cell species specificity with canine, porcine, and human peripheral blood lymphocytes indicated that the activity of the cloned leukotoxin was identical to that of the P. haemolytica leukotoxin. Furthermore, the E. coli-produced leukotoxin was also neutralized by bovine or rabbit antiserum known to have antitoxic activity. When cellular proteins from the E. coli clones were subjected to sodium dodecyl sulfate-polyacrylamide gel electrophoresis and Western blot analysis, a 100,000-dalton protein was identified which corresponded to one of the soluble antigens found in the leukotoxic culture supernatant of P. haemolytica. These results demonstrated that the gene(s) for the P. haemolytica leukotoxin have been cloned and that the leukotoxin was expressed in E. coli. Images PMID:3905610

  14. Restriction endonuclease analysis and ribotyping differentiate Pasteurella haemolytica serotype A1 isolates from cattle within a feedlot.

    PubMed Central

    Murphy, G L; Robinson, L C; Burrows, G E

    1993-01-01

    Pasteurella haemolytica serotype A1 isolates were collected from cattle within a feedlot during an outbreak of bovine respiratory disease. Genetic heterogeneity among the isolates was examined by restriction endonuclease analysis (REA), ribotyping, and analysis of plasmid content. The susceptibilities of isolates to several antibiotics were also examined. Five different REA patterns and three different ribotypes were observed among the isolates. Fifty percent of the isolates had an identical REA type, ribotype, and plasmid profile. Examination of the plasmid content of the isolates revealed that most (73%) carry a single plasmid which encodes beta-lactamase, 13.5% carry two plasmids, and 13.5% carry no plasmid. The data reveal the presence of genetic differences among isolates of P. haemolytica A1, associated with shipping fever pneumonia within a closed feedlot, and suggest that a combination of REA, ribotyping, plasmid analysis, and antibiotic susceptibility determination will be useful in analyzing the molecular epidemiology of this disease. Images PMID:7691872

  15. Cloning, nucleotide sequence, and expression of the Pasteurella haemolytica A1 glycoprotease gene.

    PubMed Central

    Abdullah, K M; Lo, R Y; Mellors, A

    1991-01-01

    Pasteurella haemolytica serotype A1 secretes a glycoprotease which is specific for O-sialoglycoproteins such as glycophorin A. The gene encoding the glycoprotease enzyme has been cloned in the recombinant plasmid pH1, and its nucleotide sequence has been determined. The gene (designated gcp) codes for a protein of 35.2 kDa, and an active enzyme protein of this molecular mass can be observed in Escherichia coli clones carrying pPH1. In vivo labeling of plasmid-encoded proteins in E. coli maxicells demonstrated the expression of a 35-kDa protein from pPH1. The amino-terminal sequence of the heterologously expressed protein corresponds to that predicted from the nucleotide sequence. The glycoprotease is a neutral metalloprotease, and the predicted amino acid sequence of the glycoprotease contains a putative zinc-binding site. The gene shows no significant homology with the genes for other proteases of procaryotic or eucaryotic origin. However, there is substantial homology between gcp and an E. coli gene, orfX, whose product is believed to function in the regulation of macromolecule biosynthesis. Images PMID:1885539

  16. The upper respiratory tract is a natural reservoir of haemolytic Mannheimia species associated with ovine mastitis.

    PubMed

    Omaleki, Lida; Browning, Glenn F; Allen, Joanne L; Markham, Philip F; Barber, Stuart R

    2015-12-31

    Lamb suckling has been suggested to be an important way of infecting a ewe's udder with different bacteria, including Mannheimia haemolytica. To test the potential role of lambs in transferring Mannheimia species to the ewe's udder, the restriction endonuclease cleavage patterns of isolates obtained from nasopharyngeal swabs were compared with those obtained from cases of mastitis. Sterile cotton swabs were used to collect nasopharyngeal samples from 50 ewes and 36 lambs from three flocks. M. haemolytica and Mannheimia glucosida as well as haemolytic Mannheimia ruminalis-like organisms were detected in the upper respiratory tract of lambs and ewes. Comparison of the restriction endonuclease cleavage patterns of the isolates suggested that the M. haemolytica isolates obtained from different milk samples from ewes with mastitis were more clonal than those obtained from the nasal swabs. However, some nasal isolates within both Mannheimia species had restriction endonuclease cleavage patterns identical to those obtained from milk samples from ewes with mastitis, indicating that lambs may have a role in transferring these organisms to the udder. More clonality was observed between the M. glucosida isolates than between M. haemolytica isolates.

  17. Sequence diversity, cytotoxicity and antigenic similarities of the leukotoxin of isolates of Mannheimia species from mastitis in domestic sheep.

    PubMed

    Omaleki, Lida; Browning, Glenn F; Barber, Stuart R; Allen, Joanne L; Srikumaran, Subramaniam; Markham, Philip F

    2014-11-07

    Species within the genus Mannheimia are among the most important causes of ovine mastitis. Isolates of these species can express leukotoxin A (LktA), a primary virulence factor of these bacteria. To examine the significance of variation in the LktA, the sequences of the lktA genes in a panel of isolates from cases of ovine mastitis were compared. The cross-neutralising capacities of rat antisera raised against LktA of one Mannheimia glucosida, one haemolytic Mannheimia ruminalis, and two Mannheimia haemolytica isolates were also examined to assess the effect that variation in the lktA gene can have on protective immunity against leukotoxins with differing sequences. The lktA nucleotide distance between the M. haemolytica isolates was greater than between the M. glucosida isolates, with the M. haemolytica isolates divisible into two groups based on their lktA sequences. Comparison of the topology of phylogenetic trees of 16S rDNA and lktA sequences revealed differences in the relationships between some isolates, suggesting horizontal gene transfer. Cross neutralisation data obtained with monospecific anti-LktA rat sera were used to derive antigenic similarity coefficients for LktA from the four Mannheimia species isolates. Similarity coefficients indicated that LktA of the two M. haemolytica isolates were least similar, while LktA from M. glucosida was most similar to those for one of the M. haemolytica isolates and the haemolytic M. ruminalis isolate. The results suggested that vaccination with the M. glucosida leukotoxin would generate the greatest cross-protection against ovine mastitis caused by Mannheimia species with these alleles. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. Evidence of bovine immunoglobulin G1 (IgG1) protease activity in partially purified culture supernate of Pasteurella haemolytica A1.

    PubMed Central

    Lee, C W; Shewen, P E

    1996-01-01

    In the bovine respiratory tract, IgG1 is a major secretory immunoglobulin (Ig), and both IgG1 and IgG2 are believed to be important in defense against pneumonic pasteurellosis (shipping fever) in calves. Here we provide evidence for hydrolysis of IgG1 in the presence of partially purified culture supernate (ppCS) from the respiratory pathogen Pasteurella haemolytica A1. Bovine IgG1 was hydrolysed sequentially into three distinct bands (approximately 39, 12, and 7 kDa respectively). Furthermore, partial hydrolysis of bovine IgG2 was observed, but neither bovine IgA nor IgM were affected by incubation with ppCS. These findings suggest that the production of an IgG1-specific protease by P. haemolytica A1 may be a virulence mechanism contributing to the pathogenesis of bovine pneumonic pasteurellosis. Images Figure 1. Figure 2. Figure 3. Figure 4. Figure 5. PMID:8785718

  19. Isolation of Pasteurella haemolytica leukotoxin mutants.

    PubMed Central

    Chidambaram, M; Sharma, B; Petras, S F; Reese, C P; Froshauer, S; Weinstock, G M

    1995-01-01

    Two mutants of Pasteurella haemolytica A1 that do not produce leukotoxin were isolated. Following mutagenesis, colonies were screened with antiserum by a filter assay for absence of the secreted leukotoxin. The two mutants both appeared to produce normal amounts of other antigens, as judged by reactivity with polyclonal serum from an animal with pasteurellosis, and were not altered in beta-hemolytic activity as seen on blood agar plates. There was no evidence of either cell-associated or secreted leukotoxin protein when Western blots (immunoblots) were carried out with the polyclonal serum or with a monoclonal antibody directed against the leukotoxin. Southern blots revealed that both mutants show the wild-type restriction pattern at the leukotoxin locus, although the strain with the lktA2 mutation showed differences in other regions of the chromosome on analysis by pulsed-field gel electrophoresis. The strain with the lktA2 mutation grew more slowly than did the wild-type strain, while the strain with the lktA1 mutation was indistinguishable from the wild-type strain in its growth properties. The strain with the lktA1 mutation should be valuable in determining the role of the leukotoxin in virulence as well as in identifying other virulence factors of P. haemolytica. PMID:7868223

  20. Characterization of neuraminidases produced by various serotypes of Pasteurella haemolytica.

    PubMed Central

    Straus, D C; Jolley, W L; Purdy, C W

    1993-01-01

    Neuraminidases produced by 16 strains of Pasteurella haemolytica (serotypes 1 to 16) were characterized by molecular weight, antigenic identity, and substrate specificity. After growth in a chemically defined medium, stage I (lyophilized) culture supernatants were assayed for activity with N-acetylneuramin lactose, human alpha-1-acid glycoprotein, fetuin, colominic acid, and bovine submaxillary mucin. Neuraminidase produced by P. haemolytica serotype A1 (Ph A1) was purified by a combination of salt fractionation, ion-exchange chromatography on DEAE-Sephacel, and gel filtration on Sephadex G-200. Purified Ph A1 neuraminidase was used to immunize rabbits, and the resultant antiserum reduced the activity of Ph A1 neuraminidase by 46%. This antiserum also reduced the activity of neuraminidase produced by the other serotypes by between 15 and 66%. Molecular weight estimates of the neuraminidases produced by the various serotypes were obtained by gel filtration chromatography on Sephadex G-200. Fifteen of the 16 serotypes examined produced a neuraminidase with a molecular weight of approximately 150,000 to 200,000. One serotype (serotype 11) produced no material with neuraminidase activity. In addition, all 15 high-molecular-weight neuraminidases showed similar substrate specificities. That is, they were all most active against N-acetylneuramin lactose and least active against bovine submaxillary mucin. On the basis of these results, it appears that the high-molecular-weight neuraminidases produced by the different P. haemolytica serotypes are quite similar. PMID:8406865

  1. Immunization of bighorn sheep against mannheimia haemolytica with a bovine herpesvirus 1-vectored vaccine

    USDA-ARS?s Scientific Manuscript database

    Pneumonia has significantly contributed to the drastic decline of bighorn sheep (BHS, Ovis canadensis) population in North America. Pneumonia outbreaks in BHS herds can incur mortalities up to 90%. Transplantation of healthy BHS into habitats that suffered pneumonia outbreaks has failed to restore B...

  2. Mycoplasma ovipneumoniae can predispose bighorn sheep to fatal Mannheimia haemolytica pneumonia

    USDA-ARS?s Scientific Manuscript database

    Mycoplasma ovipneumoniae has been isolated from the lungs of pneumonic bighorn sheep (BHS). However experimental reproduction of fatal pneumonia in BHS with M. ovipneumoniae was not successful. Therefore the specific role, if any, of M. ovipneumoniae in BHS pneumonia is unclear. The objective of th...

  3. Isolation and Characterization of Lytic Properties of Bacteriophages Specific for M. haemolytica Strains

    PubMed Central

    Urban-Chmiel, Renata; Wernicki, Andrzej; Stęgierska, Diana; Dec, Marta; Dudzic, Anna; Puchalski, Andrzej

    2015-01-01

    Aim of Study The objective of this study was isolation and morphological characterization of temperate bacteriophages obtained from M. haemolytica strains and evaluation of their lytic properties in vitro against M. haemolytica isolated from the respiratory tract of calves. Material and Methods The material for the study consisted of the reference strain M. haemolytica serotype 1 (ATCC®) BAA-410™, reference serotypes A1, A2, A5, A6, A7, A9 and A11, and wild-type isolates of M. haemolytica. Bacteriophages were induced from an overnight bacterial starter culture of all examined M. haemolytica strains treated with mitomycin C. The lytic properties and host ranges were determined by plaque assays. The morphology of the bacteriophages was examined in negative-stained smears with 5% uranyl acetate solution using a transmission electron microscope. The genetic analysis of the bacteriophages was followed by restriction analysis of bacteriophage DNA. This was followed by analysis of genetic material by polymerase chain reaction (PCR). Results Eight bacteriophages were obtained, like typical of the families Myoviridae, Siphoviridae and Podoviridae. Most of the bacteriophages exhibited lytic properties against the M. haemolytica strains. Restriction analysis revealed similarities to the P2-like phage obtained from the strain M. haemolytica BAA-410. The most similar profiles were observed in the case of bacteriophages φA1 and φA5. All of the bacteriophages obtained were characterized by the presence of additional fragments in the restriction profiles with respect to the P2-like reference phage. In the analysis of PCR products for the P2-like reference phage phi-MhaA1-PHL101 (DQ426904) and the phages of the M. haemolytica serotypes, a 734-bp phage PCR product was obtained. The primers were programmed in Primer-Blast software using the structure of the sequence DQ426904 of reference phage PHL101. Conclusions The results obtained indicate the need for further research aimed

  4. Isolation and Characterization of Lytic Properties of Bacteriophages Specific for M. haemolytica Strains.

    PubMed

    Urban-Chmiel, Renata; Wernicki, Andrzej; Stęgierska, Diana; Dec, Marta; Dudzic, Anna; Puchalski, Andrzej

    2015-01-01

    The objective of this study was isolation and morphological characterization of temperate bacteriophages obtained from M. haemolytica strains and evaluation of their lytic properties in vitro against M. haemolytica isolated from the respiratory tract of calves. The material for the study consisted of the reference strain M. haemolytica serotype 1 (ATCC®) BAA-410™, reference serotypes A1, A2, A5, A6, A7, A9 and A11, and wild-type isolates of M. haemolytica. Bacteriophages were induced from an overnight bacterial starter culture of all examined M. haemolytica strains treated with mitomycin C. The lytic properties and host ranges were determined by plaque assays. The morphology of the bacteriophages was examined in negative-stained smears with 5% uranyl acetate solution using a transmission electron microscope. The genetic analysis of the bacteriophages was followed by restriction analysis of bacteriophage DNA. This was followed by analysis of genetic material by polymerase chain reaction (PCR). Eight bacteriophages were obtained, like typical of the families Myoviridae, Siphoviridae and Podoviridae. Most of the bacteriophages exhibited lytic properties against the M. haemolytica strains. Restriction analysis revealed similarities to the P2-like phage obtained from the strain M. haemolytica BAA-410. The most similar profiles were observed in the case of bacteriophages φA1 and φA5. All of the bacteriophages obtained were characterized by the presence of additional fragments in the restriction profiles with respect to the P2-like reference phage. In the analysis of PCR products for the P2-like reference phage phi-MhaA1-PHL101 (DQ426904) and the phages of the M. haemolytica serotypes, a 734-bp phage PCR product was obtained. The primers were programmed in Primer-Blast software using the structure of the sequence DQ426904 of reference phage PHL101. The results obtained indicate the need for further research aimed at isolating and characterizing bacteriophages

  5. Fatal Pasteurella haemolytica pneumonia in bighorn sheep after direct contact with clinically normal domestic sheep.

    PubMed

    Foreyt, W J

    1989-03-01

    Six Rocky Mountain bighorn sheep were raised in captivity from birth (n = 5) or taken from the wild as a lamb (n = 1). After the bighorn sheep were in captivity for over a year, 6 clinically normal domestic sheep were placed on the 2 ha of pasture on which the bighorn sheep were kept. Nasal swab specimens were obtained from all sheep at the time the domestic sheep were introduced. Pasteurella haemolytica was isolated from swab specimens obtained from 4 of 6 domestic sheep, but not from specimens obtained from the bighorn sheep. All 6 bighorn sheep died of acute hemorrhagic pneumonia after exposure to domestic sheep. Death in the bighorn sheep occurred on days 4, 27, 27, 29, 36, or 71 after initial exposure to domestic sheep. Pasteurella haemolytica was isolated from respiratory tract tissue specimens of all bighorn sheep at the time of death. None of the domestic sheep were clinically ill during the study. At the end of the study, 3 of 6 domestic sheep were euthanatized, and at necropsy, P haemolytica was isolated from 2 of them. The most common serotypes in bighorn and domestic sheep were P haemolytica T-3 and A-2. Other serotypes isolated included P haemolytica A-1, A-9, and A-11 in bighorn sheep and A-1 in domestic sheep. On the basis of results of this study and of other reports, domestic sheep and bighorn sheep should not be managed in proximity to each other because of the potential fatal consequences in bighorn sheep.

  6. Ovine pulmonary surfactant induces killing of Pasteurella haemolytica, Escherichia coli, and Klebsiella pneumoniae by normal serum.

    PubMed Central

    Brogden, K A

    1992-01-01

    Pulmonary surfactant has been shown to play an increasingly important role in bacterial clearance at the alveolar surface in the lung. This study describes a bactericidal mechanism in which ovine pulmonary surfactant induces killing of Pasteurella haemolytica by normal serum. To demonstrate killing, six bacterial species were incubated first with pulmonary surfactant for 60 min at 37 degrees C and then with serum for an additional 60 min at 37 degrees C. P. haemolytica type A1 strains 82-25 and L101, a P. haemolytica type 2 strain, Escherichia coli, and Klebsiella pneumoniae were susceptible and Pasteurella multocida, Serratia marcescens, and Pseudomonas aeruginosa were not susceptible to killing by ovine pulmonary surfactant and normal serum. No bacteria incubated with bovine pulmonary surfactant were killed by normal serum. Although the species origin of pulmonary surfactant was selective, the species origin of serum was not. P. haemolytica incubated with ovine pulmonary surfactant was killed by fetal calf serum, gnotobiotic calf serum, pooled normal sheep serum, pooled normal rabbit serum, and pooled guinea pig serum. Ultrastructurally, killed P. haemolytica suspensions contained dead cells and cells distorted with vacuoles between the cytoplasmic membrane and the cytoplasm. The mechanism of killing did not correlate with concentrations of complement or lysozyme or titers of residual antibody in either the pulmonary surfactant or the serum, and killing was reduced by preincubation of surfactant with P. haemolytica lipopolysaccharide. Preliminary characterization of both surfactant and serum implicate a low-molecular-weight proteinaceous component in the surfactant and serum albumin in the serum. This mechanism may help clear certain gram-negative bacteria from the lungs of sheep as a part of the pulmonary innate defense system. Images PMID:1452351

  7. Human Wound Infection with Mannheimia glucosida following Lamb Bite

    PubMed Central

    Omaleki, Lida; Turni, Conny; Barber, Stuart Richard; Francis, Michelle J.; Graham, Maryza

    2015-01-01

    Mannheimia spp. are veterinary pathogens that can cause mastitis and pneumonia in domestic cattle and sheep. While Mannheimia glucosida can be found as normal flora in oral and respiratory mucosa in sheep, there have been no reported cases of human infection with this organism. PMID:26202121

  8. The effect of Pasteurella haemolytica and the leukotoxin of Pasteurella haemolytica on bovine lung explants.

    PubMed Central

    Wilkie, I W; Fallding, M H; Shewen, P E; Yager, J A

    1990-01-01

    Bovine lung explants were used in a study designed to compare the pathogenic effects of Pasteurella haemolytica type 1, a nonpathogenic organism Neisseria subflava, or the crude leukotoxin of P. haemolytica on alveolar macrophages and lung parenchymal cells. Concentrated, purified peripheral blood neutrophil suspensions were added with the bacteria to some explants. Duplicate pairs of cultures from each treatment group were fixed at regular intervals up to 24 hours after seeding and morphological changes were assessed by light and electron microscopy. Pasteurella haemolytica caused deterioration of alveolar macrophages within one hour but did not affect parenchymal cells for more than 12 hours. Neisseria subflava did not affect alveolar macrophages initially, but caused an accelerated deterioration after four hours. After 24 hours, bacterial overgrowth caused similar deterioration of all cells in explants seeded with either bacterium. Alveolar macrophages phagocytosed large numbers of N. subflava but rarely ingested P. haemolytica. Added neutrophils did not have any discernible effect on any of the explants and did not potentiate bacterial effects. Addition of crude leukotoxin of P. haemolytica to the culture medium significantly accelerated alveolar macrophage deterioration without apparent effect on parenchymal cell survival. These results support the hypothesis that the severe tissue destruction of fulminant pneumonic pasteurellosis is not a direct result of bacterial infection. Images Fig. 1. Fig. 2. Fig. 3. Fig. 4. Fig. 5. Fig. 6. Fig. 7. Fig. 8. PMID:2306666

  9. Conservation of Expression and N-Terminal Sequences of the Pasteurella haemolytica 31-Kilodalton and Pasteurella trehalosi 29-Kilodalton Periplasmic Iron-Regulated Proteins

    PubMed Central

    Tabatabai, Louisa B.; Frank, Glynn H.

    1999-01-01

    This study examined the conservation of expression of a 31-kDa iron-regulated protein by serotypes of Pasteurella haemolytica and Pasteurella trehalosi associated with pasteurellosis of cattle and sheep. A polyclonal antibody prepared against the purified 31-kDa periplasmic iron-regulated protein from P. haemolytica serotype A1 showed that all P. haemolytica serotypes expressed similar 31-kDa proteins with identical N-terminal sequences, whereas P. trehalosi serotypes expressed immunologically different 29-kDa proteins with a different N-terminal sequence. Antibody to the 31-kDa iron-regulated protein was a useful tool to distinguish similarities and differences of the iron-regulated proteins of P. haemolytica and P. trehalosi. PMID:10391874

  10. Susceptibility of Rocky Mountain bighorn sheep and domestic sheep to pneumonia induced by bighorn and domestic livestock strains of Pasteurella haemolytica.

    PubMed

    Onderka, D K; Rawluk, S A; Wishart, W D

    1988-10-01

    Bighorn sheep were inoculated intratracheally with suspensions of nonhemolytic Pasteurella haemolytica biotype T (10(12) organisms) unique to wild bighorns, with beta-hemolytic P. haemolytica biotype T (10(12) organisms) isolated from clinically normal domestic sheep or intradermally with half a dose of a cattle vaccine containing P. haemolytica biotype A (10(5) organisms). The bighorn strain caused lobar necrotizing bronchopneumonia whereas both domestic livestock strains precipitated fatal septicemia and fibrinous bronchopneumonia. The serotypes given were T3, T4, T15 and A1 and these were recovered from lung lesions and other organs. In three trials, domestic sheep were inoculated intratracheally with suspensions of bighorn sheep pneumonic lungs, and two concentrations of the P. haemolytica bighorn strain (10(4) and 10(12) organisms). One of these sheep was inoculated intrabronchially. The domestic sheep experienced a transient fever and elevated white blood cell counts. After six days, none of the sheep had lung lesions and inoculated organisms could not be recovered. It is suggested that bighorn sheep are very susceptible to P. haemolytica from domestic livestock and should not be allowed in contact with sheep or cattle.

  11. Susceptibility of Rocky Mountain bighorn sheep and domestic sheep to pneumonia induced by bighorn and domestic livestock strains of Pasteurella haemolytica.

    PubMed Central

    Onderka, D K; Rawluk, S A; Wishart, W D

    1988-01-01

    Bighorn sheep were inoculated intratracheally with suspensions of nonhemolytic Pasteurella haemolytica biotype T (10(12) organisms) unique to wild bighorns, with beta-hemolytic P. haemolytica biotype T (10(12) organisms) isolated from clinically normal domestic sheep or intradermally with half a dose of a cattle vaccine containing P. haemolytica biotype A (10(5) organisms). The bighorn strain caused lobar necrotizing bronchopneumonia whereas both domestic livestock strains precipitated fatal septicemia and fibrinous bronchopneumonia. The serotypes given were T3, T4, T15 and A1 and these were recovered from lung lesions and other organs. In three trials, domestic sheep were inoculated intratracheally with suspensions of bighorn sheep pneumonic lungs, and two concentrations of the P. haemolytica bighorn strain (10(4) and 10(12) organisms). One of these sheep was inoculated intrabronchially. The domestic sheep experienced a transient fever and elevated white blood cell counts. After six days, none of the sheep had lung lesions and inoculated organisms could not be recovered. It is suggested that bighorn sheep are very susceptible to P. haemolytica from domestic livestock and should not be allowed in contact with sheep or cattle. Images Fig. 1. Fig. 2. Fig. 3. PMID:3196974

  12. Pasteurella haemolytica complicated respiratory infections in sheep and goats.

    PubMed

    Brogden, K A; Lehmkuhl, H D; Cutlip, R C

    1998-01-01

    Respiratory infections which commonly occur in sheep and goats often result from adverse physical and physiological stress combined with viral and bacterial infections. Inevitably, Pasteurella haemolytica pneumonia occurs as a result of these interactions. In this review, we present recent advances in research on the complex etiology of pneumonia involving P. haemolytica. Initially stress, induced by factors such as heat, overcrowding, exposure to inclement weather, poor ventilation, handling and transport is a major predisposing factor. Respiratory viruses including parainfluenza 3 (PI-3) virus, adenovirus type 6 and respiratory syncytial virus (RSV), and to a lesser extent bovine adenovirus type 2, ovine adenovirus types 1 and 5, and reovirus type 1 cause respiratory infections and pneumonia. More importantly these viruses also dramatically increase the susceptibility of sheep and goats to secondary P. haemolytica infection. Primary infection of the lower respiratory tract, with Mycoplasma ovipneumoniae and Bordetella parapertussis can increase the susceptibility of sheep and goats to secondary P. haemolytica infection. It is possible that initial infections with viral or primary bacterial agents break down the antimicrobial barrier consisting of beta defensins and anionic peptides found in epithelial cells, resident and inflammatory cells, and serous and mucous secretions of the respiratory tract. Loss of barrier integrity may release P. haemolytica from its usual commensal status. Once in the lung, P. haemolytica becomes opportunistic. To grow and colonize, P. haemolytica uses extracellular products like O-sialoglycoprotein endopeptidase, neuraminidase and RTX leukotoxin, as well as cell-associated products such as capsular polysaccharide, lipopolysaccharide, outer membrane proteins, proteins involved in iron acquisition and a periplasmic superoxide dismutase. In lambs and kids, pneumonic pasteurellosis can be acute, characterized by fever, listlessness, poor

  13. Isolation of Pasteurella haemolytica from grass, drinking water, and straw bedding used by sheep.

    PubMed

    Burriel, A R

    1997-11-01

    Pasteurella haemolytica was isolated from three of 18 grass samples and four of 18 water samples collected from two grazing fields occupied by sheep. This microorganism was also isolated from three of nine straw bedding samples collected from a pen housing ewes affected by mastitis caused by P. haemolytica. The same ewes developed scabbed papilloma-like lesions on the teat and udder skin. These lesions were colonized by P. haemolytica of various serotypes. Colder, wetter weather seems to prolong the survival of P. haemolytica in the environment of sheep. Survival of virulent strains of P. haemolytica in the environment could accumulatively increase the bacterial count, contributing to their transmission from animal to animal. The preference of P. haemolytica for colder, wetter conditions was confirmed in the laboratory where this microorganism survived longer in distilled water, phosphate-buffered saline, Todd-Hewitt broth, and ewe's milk kept at 4 degrees C.

  14. Antigenic and virulence properties of Pasteurella haemolytica leukotoxin mutants.

    PubMed Central

    Petras, S F; Chidambaram, M; Illyes, E F; Froshauer, S; Weinstock, G M; Reese, C P

    1995-01-01

    Antigenic properties of two mutants of Pasteurella haemolytica, strains 59B0071 and 59B0072, that do not produce detectable leukotoxin were investigated. Western blot (immunoblot) analysis with a number of polyclonal sera from animals recovering from pasteurellosis revealed that both mutants secreted a variety of antigens that were also present in cultures of several wild-type strains. These antigens ranged from about 100 to 15 kDa. Mutant strain 59B0071 was found to be totally deficient in leukotoxin, as judged not only by Western blotting but also by cytotoxicity assays with bovine lymphoma (BL-3) cells or bovine polymorphonuclear cells as targets. The mutant strain 59B0071 had normal levels of a secreted sialylglycoprotease, however. When strains were tested for virulence in goat and cattle challenge experiments, a reduction in mortality and lung lesions was observed with the mutant 59B0071 in comparison with results obtained with wild-type strains. These results are consistent with an important role for leukotoxin in P. haemolytica virulence and suggest that leukotoxin-negative mutants may be useful tools in the investigation of other virulence properties involved in P. haemolytica infections. PMID:7868224

  15. Pasteurella haemolytica antigens associated with resistance to pneumonic pasteurellosis.

    PubMed Central

    Mosier, D A; Simons, K R; Confer, A W; Panciera, R J; Clinkenbeard, K D

    1989-01-01

    Antigens associated with whole Pasteurella haemolytica biotype A serotype 1, a capsular carbohydrate-protein extract of the organism, and P. haemolytica leukotoxin were separated by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Antigens of the electrophoresed preparations were detected by Western blotting (immunoblotting) with sera from cattle which were either nonvaccinated or vaccinated with live or killed P. haemolytica vaccines and had variable degrees of resistance to experimental pneumonic pasteurellosis. Distinct, easily recognizable antigens of these preparations were identified, and the antibody responses to these antigens were quantified by densitometry. To determine their importance to disease resistance, we then compared antibody responses with experimental lesion scores. Antibody reactivity to surface antigens which were significantly correlated with resistance and present in two or more of the preparations were detected at 86, 66, 51, 49, 34, 31, and 16 kilodaltons (kDa). Of these, antibody responses to antigens at 86, 49, and 31 kDa appeared most important based on their concentration and significance levels. Antibody reactivity to leukotoxin antigens which were significantly correlated with resistance and common with important surface antigens were detected at 86, 66, and 49 kDa. Antibody responses to unique leukotoxin antigens which were significantly correlated with resistance were present at 92 and 58 kDa. Images PMID:2917783

  16. Secretion and expression of the Pasteurella haemolytica Leukotoxin.

    PubMed Central

    Highlander, S K; Engler, M J; Weinstock, G M

    1990-01-01

    The Pasteurella haemolytica leukotoxin gene cluster (lktCABD) is homologous to the Escherichia coli hemolysin locus (hlyCABD). Since the cloned leukotoxin (LktA) is not secreted from E. coli cells, a heteroplasmid complementation system was developed that permits secretion of the leukotoxin from cells expressing the hemolysin transport proteins HlyB and HlyD. We observed that the secreted leukotoxin protein had weak hemolytic activity when activated by either the HlyC or LktC proteins and that LktC expressed in E. coli could confer weak hemolytic activity upon hemolysin. Thus, it appears that the accessory proteins of the leukotoxin and hemolysin gene clusters are functionally similar, although their expression in E. coli is not equivalent. Northern (RNA) blot analysis of the P. haemolytica leukotoxin gene cluster revealed a major 3.5-kilobase transcript that includes the lktC and lktA genes. The start site for this transcript mapped to a cytosine residue 30 nucleotides upstream from the putative start of lktC; a similar initiation site was observed in E. coli, although adjacent cytosine and adenine residues were also utilized. The 3.5-kilobase transcript terminated near the rho-independent terminator structure between lktA and lktB, but transcription may continue, via antitermination or de novo transcription initiation, into the downstream lktB and lktD genes. We propose that the lack of LktB and LktD function in E. coli is a result, at least in part, of poor lktBD transcription and suggest that a P. haemolytica-specific regulator is required for optimal expression of the leukotoxin genes. Images PMID:2185213

  17. Pasteurella haemolytica bacteriophage: identification, partial characterization, and relationship of temperate bacteriophages from isolates of Pasteurella haemolytica (biotype A, serotype 1).

    PubMed

    Richards, A B; Renshaw, H W; Sneed, L W

    1985-05-01

    Pasteurella haemolytica (biotype A, serotype 1) isolates (n = 15) from the upper respiratory tract of clinically normal cattle, as well as from lung lesions from cases of fatal bovine pasteurellosis, were examined for the presence of bacteriophage after irradiation with UV light. Treatment of all P haemolytica isolates with UV irradiation resulted in lysis of bacteria due to the induction of vegetative development of bacteriophages. The extent of growth inhibition and bacterial lysis in irradiated cultures was UV dose-dependent. Bacterial cultures exposed to UV light for 20 s reached peak culture density between 60 and 70 minutes after irradiation; thereafter, culture density declined rapidly, so that by 120 minutes, it was approximately 60% of the original value. When examined ultrastructurally, lytic cultures from each isolate revealed bacteriophages with an overall length of approximately 200 nm and that appeared to have a head with icosahedral symmetry and a contractile tail. Cell-free filtrate from each noninduced bacterial isolate was inoculated onto the other bacterial isolates in a cross-culture sensitivity assay for the presence of phages lytic for the host bacterial isolates. Zones of lysis (plaques) did not develop when bacterial lawns grown from the different isolates were inoculated with filtrates from the heterologous isolates.

  18. Susceptibility of Dall sheep (Ovis dalli dalli) to pneumonia caused by Pasteurella haemolytica.

    PubMed

    Foreyt, W J; Silflow, R M; Lagerquist, J E

    1996-10-01

    We evaluated susceptibility of Dall sheep (Ovis dalli dalli) to bacterial pneumonia induced by two strains of Pasteurella haemolytica of domestic sheep origin by evaluating the sensitivity of blood neutrophils of eight Dall sheep to lysis by cytotoxins of P. haemolytica, and by intratracheal inoculation of three Dall sheep, two bighorn sheep (Ovis canadensis), and two domestic sheep with 3.7 x 10(6) or 2.5 x 10(7) colony forming units of P. haemolytica. Neutrophils from the Dall sheep were more sensitive to lysis by cytotoxins from supernatants of a P. haemolytica, biotype A, serotype 2 (A2), of domestic sheep origin, than were neutrophils from six bighorn sheep. This cytotoxic bacterium was the same isolate that was used for intratracheal inoculation of two Dall sheep and two domestic sheep. Inoculation of this cytotoxic P. haemolytica A2 resulted in fatal fibrinopurulent pleuropneumonia in the first Dall sheep within 24 hr of inoculation, and pneumonic lesions in the second Dall sheep before it was euthanized 52 hr after inoculation. This strain of P. haemolytica A2 did not cause respiratory disease when inoculated into two domestic sheep. A noncytotoxic strain of P. haemolytica; biotype T, serotype 3,4,10 of domestic sheep origin did not result in pneumonia in the third Dall sheep or two bighorn sheep. Prior to inoculation, P. haemolytica, biotype T isolates were obtained from all three Dall sheep, but none of these isolates was cytotoxic. At necropsy, cytotoxic P. haemolytica A2 was isolated from lungs and other tissues of the two pneumonic Dall sheep. Based on these results, we conclude that Dall sheep appear to be at least as sensitive as bighorn sheep to pneumonia caused by P. haemolytica A2 of domestic sheep origin. Because in vitro and in vivo results appear closely correlated in this and other studies, we believe with additional evaluation and standardization, neutrophil cytotoxicity tests may serve as a substitute for live animal challenges in future

  19. Influence of a Saccharomyces cerevisia fermentation product on the pathophysiological response to a combined intranasal bovine herpesvirus-1 and intratracheal Mannheimia haemolytica challenge in Holstein steers

    USDA-ARS?s Scientific Manuscript database

    The objective of this study was to determine the effects of supplementing a Saccharomyces cerevisiae fermentation product prototype (Prototype) on the pathophysiological response during a combined viral-bacterial respiratory challenge. Holstein steer calves (126.5±6.11kg; N=16) were completely rando...

  20. Bovine gamma delta T cells contribute to exacerbated IL-17 production in response to co-infection with Bovine RSV and Mannheimia haemolytica

    USDA-ARS?s Scientific Manuscript database

    Human respiratory syncytial virus (HRSV) is a leading cause of severe lower respiratory tract infection in children under five years of age. IL-17 and Th17 responses are increased in children infected with HRSV and have been implicated in both protective and pathogenic roles during infection. Bovi...

  1. Proteolysis of sialoglycoprotein by Pasteurella haemolytica cytotoxic culture supernatant.

    PubMed Central

    Otulakowski, G L; Shewen, P E; Udoh, A E; Mellors, A; Wilkie, B N

    1983-01-01

    Proteolytic enzyme activity releasing sialo glycopeptides from 3H-labeled human erythrocyte ghosts was detected in cytotoxic (leukotoxic) culture supernatants from 9 of 12 Pasteurella haemolytica serotypes. Microcrystalline cellulose thin-layer chromatograms of radioactive water-soluble products showed the following two radioactive peaks: a high-mobility minor peak (Rf, 0.54 to 0.74), identified as sialic acid, and a low-mobility major peak (Rf, 0.18 to 0.21), partially characterized as a trichloroacetic acid-soluble, sialic acid-rich fragment with a molecular weight of greater than 3,500, not extractable by chloroform. The sialic acid content of this fragment after treatment with Clostridium perfringens neuraminidase was estimated to be 7.2 X 10(-2) mumol mg-1. The presence of neuraminidase as a separate activity in some culture supernatants was confirmed. It is considered to be responsible for the observed release of free sialic acid. Preliminary studies with the crude enzyme showed that it has a broad pH optimum around pH 7.0 and that activity is not affected by inhibitors of trypsin, chymotrypsin, thermolysin, thio and serine enzymes, nor by an inhibitor of neuraminidase, 2,3-dehydro-2-deoxy-N-acetylneuraminic acid. Activity was, however, inhibited by o-phenanthroline at a high concentration after prolonged treatment. The enzyme hydrolyzed glycophorin at a rate four times higher than the rate for casein. Free glycophorin inhibited the enzyme-induced release of radioactive products from 3H-labeled ghosts. It is speculated that the novel enzyme is a neutral protease, probably metal-dependent, with specificity for sialoglycopeptides. The possible relationship of this protease to the previously reported host species-specific leukotoxicity of P. haemolytica and its potential role in virulence is discussed. PMID:6352504

  2. Susceptibility of phagocytes from elk, deer, bighorn sheep, and domestic sheep to Pasteurella haemolytica cytotoxins.

    PubMed

    Silflow, R M; Foreyt, W J

    1994-10-01

    Alveolar macrophages and peripheral blood neutrophils from elk (Cervus elaphus), bighorn sheep (Ovis canadensis canadensis), and domestic sheep were exposed to culture supernatants from Pasteurella haemolytica isolated from bighorn sheep and domestic sheep. In a second experiment, peripheral blood neutrophils from mule deer (Odocoileus hemionus), elk, and bighorn sheep were exposed to culture supernatants from P. haemolytica isolated from elk, bighorn sheep and domestic sheep. Alveolar macrophages from elk, bighorn sheep and domestic sheep were resistant to killing by P. haemolytica supernatants from bighorn sheep and domestic sheep; susceptibility of neutrophils to cell death, as measured by release of lactate dehydrogenase, differed significantly (P < 0.05) between the four species tested. Bighorn sheep and domestic sheep neutrophils were susceptible to cytotoxin damage by the P. haemolytica isolates used; bighorn sheep neutrophils were four- to eight-fold more susceptible to cytotoxin damage than domestic sheep neutrophils. Neutrophils from deer and elk were resistant to killing by P. haemolytica cytotoxins from any species tested.

  3. Fatal pneumonia following inoculation of healthy bighorn sheep with Pasteurella haemolytica from healthy domestic sheep.

    PubMed

    Foreyt, W J; Snipes, K P; Kasten, R W

    1994-04-01

    In a series of three experiments, isolates of Pasteurella haemolytica biotype A, serotype 2, ribotype reference WSU-1, from healthy domestic sheep, were inoculated intratracheally into eight bighorn sheep (Ovis canadensis canadensis) and seven domestic sheep with doses of bacteria ranging from 5.3 x 10(8) to 8.6 x 10(11) colony forming units. Seven of eight inoculated bighorn sheep died from acute pneumonia within 48 hr of inoculation, whereas all seven domestic sheep inoculated with comparable or greater doses of bacteria remained healthy. One contact control bighorn sheep also died 6 days after its penmates received P. haemolytica. Three other noncontact control bighorn sheep remained healthy during the experiments. Pasteurella haemolytica biotype A, serotype 2, ribotype reference WSU-1 in the inocula was recovered from one or more tissues from all bighorns that died; whereas, it was not detected in any bighorn sheep before inoculation. Three different ribotypes of P. haemolytica A2 were recovered from bighorn sheep; however, only the ribotype reference WSU-1 in the domestic sheep-origin inoculum was recovered from all dead bighorn sheep, and was not recovered from bighorn sheep that survived the experiments. Thus, a relatively nonpathogenic and common isolate of P. haemolytica from healthy domestic sheep was lethal in bighorn sheep under experimental conditions.

  4. The pulmonary clearance of Pasteurella haemolytica in calves infected with bovine virus diarrhea or Mycoplasma bovis.

    PubMed Central

    Lopez, A; Maxie, M G; Savan, M; Ruhnke, H L; Thomson, R G; Barnum, D A; Geissinger, H D

    1982-01-01

    Based on current literature which commonly associates bovine virus diarrhea virus and Mycoplasma bovis with "pneumonic pasteurellosis," an investigation was conducted into the effect of these two pathogens on the capacity of bovine lung to clear inhaled Pasteurella haemolytica. There was no significant effect (p less than 0.05) of either bovine virus diarrhea virus or M. bovis on the mean clearance rate of P. haemolytica, nor did the time interval of three, five or seven days between the first inoculation and exposure to P. haemolytica and adversely affect the lung clearance rates. However, it was found that the left lungs and a higher bacterial retention (p less than 0.05) than the right lungs. PMID:7127194

  5. Pasteurella haemolytica ultraviolet-irradiated vaccine by parenteral and aerosol routes compared in the goat model.

    PubMed

    Purdy, C W; Cooley, J D; Straus, D C

    1998-08-01

    Positive control 1 (PC1) (n = 9) goats were injected transthoracically into the left lung with live Pasteurella haemolytica biovar A, serovar 1 (PhA1) in polyacrylate (PA) beads on days 0 and 21. Positive control 2 (PC2) (n = 6) goats were nebulized with live PhA1 and PA beads on days 0 and 21. Negative control (NC) goats (n = 6) were each injected transthoracically into the left lung with PA beads alone on days 0 and 21. Four groups (n = 6) were administered PA beads mixed with ultraviolet (UV) killed PhA1 on days 0 and 21. The treatment doses of bacteria for these groups were principal group 1 (PR1) injected into the left lung (7.7 x 10(10) cfu); PR2, 7.7 x 10(10) UV-killed PhA1 injected subcutaneously (SC); PR3, 7.7 x 10(10) UV-killed PhA1 injected SC only on day 21; PR4, nebulized with PA beads mixed with 5.6 x 10(10) cfu of UV-killed PhA1; and PR5, nebulized with PA beads mixed with 5 x 10(8) cfu of UV-killed PhA1. All goats were challenged transthoracically in the right lung with 1 x 10(8) cfu of live PhA1 on day 42 and necropsied on day 46. The sizes of consolidated lung lesions at the challenge site were used as a measure of immunity. The data show that the introduction of live PhA1 into the lungs of goats, either by injection or aerosolization, offers excellent protection against a subsequent homologous challenge. The data also demonstrate that two transthoracic injections (21 days apart) of UV-killed PhA1 (PR1), and subcutaneous injection of UV-killed PhA1(PR2) also offer excellent protection against a subsequent homologous live PhA1 challenge. One SC injection of UV-killed PhA1 (PR3) appears to offer only partial protection against a subsequent homologous live PhA1 challenge. Inhalation of UV-killed PhA1 mixed with PA beads (PR4 and PR5) induced no protection in goats against a subsequent live PhA1 transthoracic challenge.

  6. Pasteurella haemolytica serotype 2 contains the gene for a noncapsular serotype 1-specific antigen.

    PubMed Central

    Gonzalez, C T; Maheswaran, S K; Murtaugh, M P

    1995-01-01

    An ssa1-homologous genomic fragment cloned from Pasteurella haemolytica serotype 2 (ST2) enabled transformation of Escherichia coli DH5 alpha to a serotype 1 (ST1) phenotype through expression of the ST1-specific antigen (Ssa1). The Ssa1 protein expressed by ssa1-transformed E. coli was susceptible to heat and protease treatment and was distinct from P. haemolytica ST1-specific capsular polysaccharide. Electrophoretic analysis of in vitro-translated proteins, as well as the predicted amino acid sequence, demonstrated that Ssa1 proteins encoded from either ST1- or ST2-derived ssa1 genes were essentially identical. A comparison of the nucleotide sequences of ssa1 genes derived from P. haemolytica ST1 and ST2 revealed greater than 99% homology. Amino acid sequence homology of the predicted products of ST1- and ST2-derived ssa1 genes was greater than 98%. Northern (RNA) blot studies revealed that the presence of an increased level of ssa1 transcript in P. haemolytica ST1 grown as surface-adherent cultures on solid medium was correlated with a serologically detectable Ssa1 protein. Expression of the ssa1 transcript in ST1 was similarly upregulated by a high iron concentration in the growth medium. PMID:7890392

  7. Effect of simulated stress on susceptibility of bighorn sheep neutrophils to Pasteurella haemolytica leukotoxin.

    PubMed

    Kraabel, B J; Miller, M W

    1997-07-01

    We examined the effects of simulated stress on susceptibility of Rocky Mountain bighorn sheep (Ovis canadensis canadensis) neutrophils to Pasteurella haemolytica leukotoxin in a blocked, crossover experiment. Ten captive-raised bighorn sheep were sampled 10 hr after separate administrations of long-acting adrenocorticotrophic hormone (ACTH) gel and normal saline (control). We then compared in vitro leukotoxin-dependent neutrophil death rates after exposure to culture supernatants from four unique P. haemolytica isolates (one from domestic and three from bighorn sheep). Simulated stress effects were evidenced by elevated (P = 0.002) mean plasma cortisol concentrations, more neutrophils (P = 0.037), and fewer lymphocytes and eosinophils (P < or = 0.043) in ACTH-treated bighorn sheep. Maximum leukotoxin-dependent neutrophil death rates were > or = 61% for three of four P. haemolytica isolates tested. For all three cytotoxic isolates, neutrophil death rates at 150 micrograms/50 microliters supernatant were about 1.13 times higher (P = 0.0001) after bighorns received ACTH; for two of these, overall neutrophil death rates were higher (P < or = 0.001) in ACTH-treated bighorn sheep. Although variable leukotoxin production among P. haemolytica strains appeared principally responsible for differences in leukotoxin-dependent neutrophil death rates, susceptibility of bighorn sheep neutrophils to leukotoxin was increased by prior exposure to elevated plasma cortisol concentrations. It follows that if similar processes occur in neutrophils and alveolar macrophages in vivo, they could contribute to greater susceptibility of stressed bighorn sheep to pneumonic pasteurellosis.

  8. A Quantitative Flurometric Assay for the Measurement of Antibody to Pasteurella haemolytica in Cattle

    PubMed Central

    Confer, A.W.; Fox, J.C.; Newman, P.R.; Lawson, G.W.; Corstvet, R.E.

    1983-01-01

    A rapid, simple fluorometric method is described for measuring antibody to Pasteurella haemolytica in sera of cattle. Various antigen preparations were compared for the test including live, formalin-killed and phenol-killed P. haemolytica. A preparation composed of formalin-killed organisms from a 22 hour culture gave consistent results and was used in the studies. The test was reproduciable with percent coefficients of variation for fluorescent signal unit values on ten or more replicate samples ranging from 5.7 to 28.0. Sera from calves vaccinated by aerosol exposure to live P. haemolytica had up to a five-fold increase in antibody titer as measured by the flurometric method test during a 21 day period. Fluorometric method titers were comparable to those obtained by the indirect bacterial agglutination test. There was no seroconversion to P. haemolytica in calves vaccinated by aerosol exposure of P. multocida. The major advantages of the fluorometric method test over conventional methods are that the assay does not require serial dilutions of serum samples and thus limits time and effort to determine antibody titers. PMID:6339016

  9. Udder orf infection and its role in ovine clinical mastitis caused by Pasteurella haemolytica.

    PubMed

    Burriel, A R

    1997-04-01

    During an experimental study of ovine subclinical mastitis caused by coagulase-negative staphylococci, an outbreak of contagious ecthyma occurred among ewes unvaccinated against parapox virus. The same group of ewes developed a high rate (43.7%) of clinical mastitis caused by Pasteurella haemolytica. The rate of clinical mastitis among ewes vaccinated against parapox virus was very low (3.7%) suggesting that the presence of orf in the unvaccinated ewes was contributing to the high rate of clinical mastitis. An examination of the iron, sodium, potassium and albumin concentration of milk collected from 16 unvaccinated and nine randomly selected vaccinated ewes before experimental infection with coagulase-negative staphylococci or their uninfected control mammary glands indicated significant differences in the iron (p < 0.0001) and sodium (p = 0.01) concentration. Increased iron concentration in the milk may have assisted in the development of udder infection caused by P. haemolytica as iron is easily utilised by this bacterium.

  10. Tracheal versus pulmonary deposition and clearance of inhaled Pasteurella haemolytica or Staphylococcus aureus in mice.

    PubMed Central

    Rodríguez, L M; López, A; Merino-Moncada, M; Martínez-Burnes, J; Mondragón, I

    1985-01-01

    The aim of this investigation was to do a comparative study on the deposition and clearance of inhaled bacteria between the lungs and tracheae of mice exposed to aerosols of bacteria. Two hundred and eighty-eight mice were divided into four groups (n = 72) and exposed to aerosols of Pasteurella haemolytica or Staphylococcus aureus in four replicates. The numbers of bacteria were determined in the trachea and lungs of mice sacrificed 0, 2, 4, 8, 12, 24, 48 and 72 hours postexposure. Results indicated that bacterial deposition was greater in lungs than in tracheae. No significant (p greater than 0.05) difference was observed between P. haemolytica and S. aureus clearance rates. Although bacteria were rapidly eliminated from the whole respiratory tract, bacterial clearance was significantly (p less than 0.002) faster in tracheae than lungs. A significant (p less than 0.05) replicate effect was also observed. PMID:4041977

  11. Attempted protection of bighorn sheep (Ovis canadensis) from pneumonia using a nonlethal cytotoxic strain of Pasteurella haemolytica, biotype A, serotype.

    PubMed

    Foreyt, W J; Silflow, R M

    1996-04-01

    Between February and April, 1994, we tested the hypothesis that bighorn sheep (Ovis canadensis canadensis) inoculated with a cytotoxic isolate of Pasteurella haemolytica biotype A, serotype 11 (A11) could withstand challenge inoculation with a cytotoxic strain of P. haemolytica A2 of domestic sheep origin known to cause lethal pneumonia in bighorn sheep. On experimental day O, two bighorn sheep were inoculated intratracheally with 6 x 10(9) colony forming units (cfu) of a cytotoxic strain of P. haemolytica A11 (group 1); two bighorn sheep were inoculated intratracheally with 6 x 10(9) cfu of a noncytotoxic P. haemolytica A11 (group 2), and two control bighorn sheep were inoculated intratracheally with a similar volume of brain heart infusion (BHI) broth (group 3). After inoculation, all bighorn sheep remained healthy. On experimental day 16, group 1 bighorn sheep each were given the same intratracheal inoculation as on day O, and groups 2 and 3 bighorn sheep each were inoculated with BHI broth at the same volume as group 1. All bighorn sheep remained healthy following inoculations. On experimental day 42, bighorn sheep in groups 1 and 3 each were challenged with an intratracheal inoculation of 6 x 10(9) cfu of P. haemolytica A2 of domestic sheep origin known to be lethal in bighorn sheep. Group 2 sheep each were inoculated intratracheally with BHI broth at the same volume as groups 1 and 3. The four bighorn sheep in groups 1 and 3 that received the challenge inoculation died from acute bronchopneumonia within 72 hours after challenge inoculation, and cytotoxic P. haemolytica A2 was isolated from the four dead bighorn sheep. Both cytotoxic or noncytotoxic strains of P. haemolytica A11 were not lethal and did not cause pneumonia in the experimentally inoculated bighorn sheep. However, previous inoculation with cytotoxic P. haemolytica A11 did not protect the bighorn sheep against later experimental challenge inoculation with a known lethal strain of cytotoxic P

  12. Experimental contact transmission of Pasteurella haemolytica from clinically normal domestic sheep causing pneumonia in Rocky Mountain bighorn sheep.

    PubMed

    Onderka, D K; Wishart, W D

    1988-10-01

    Two Rocky Mountain bighorn lambs (Ovis canadensis canadensis) were held in captivity for 120 days before being housed with two domestic sheep. The lambs were clinically normal and had no Pasteurella spp. on nasal swab cultures. The domestic sheep were known to carry Pasteurella haemolytica biotype A in the nasal passages. After being in close contact for 19 days. P. haemolytica biotype A was cultured from nasal swabs of one of the bighorn lambs. By 26 days, both bighorn sheep developed coughs, were anorectic and became lethargic and nasal swabs yielded P. haemolytica biotype T, serotype 10. Twenty-nine days after contact, the lambs were necropsied and found to have extensive fibrinous bronchopneumonia. From affected tissues pure cultures of beta-hemolytic P. haemolytica biotype T, serotype 10 were grown. Both domestic sheep remained clinically normal and had no gross or microscopic lesions, but they carried the same P. haemolytica serotype in their tonsils. Behavioural observations gave no indication of stress in the bighorn lambs.

  13. 21 CFR 522.313c - Ceftiofur sodium.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae... treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica... for use. For treatment of sheep respiratory disease (sheep pneumonia) associated with Mannheimia...

  14. 21 CFR 522.313c - Ceftiofur sodium.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... bacterial respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae... treatment of bovine respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica... for use. For treatment of sheep respiratory disease (sheep pneumonia) associated with Mannheimia...

  15. 21 CFR 522.313c - Ceftiofur sodium.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella... respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and... for use. For treatment of sheep respiratory disease (pneumonia) associated with M. haemolytica and P...

  16. 21 CFR 522.313c - Ceftiofur sodium.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella... respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and... for use. For treatment of sheep respiratory disease (pneumonia) associated with M. haemolytica and P...

  17. 21 CFR 522.313c - Ceftiofur sodium.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... respiratory disease (swine bacterial pneumonia) associated with Actinobacillus pleuropneumoniae, Pasteurella... respiratory disease (shipping fever, pneumonia) associated with Mannheimia haemolytica, P. multocida, and... for use. For treatment of sheep respiratory disease (pneumonia) associated with M. haemolytica and P...

  18. Influence of β2-Integrin Adhesion Molecule Expression and Pulmonary Infection with Pasteurella haemolytica on Cytokine Gene Expression in Cattle

    PubMed Central

    Lee, Haa-Yung; Kehrli, Marcus E.; Brogden, Kim A.; Gallup, Jack M.; Ackermann, Mark R.

    2000-01-01

    β2-Integrins are leukocyte adhesion molecules composed of alpha (CD11a, -b, -c, or -d) and beta (CD18) subunit heterodimers. Genetic CD18 deficiency results in impaired neutrophil egress into tissues that varies between conducting airways and alveoli of the lung. In this study, we investigated whether CD18 deficiency in cattle affects proinflammatory cytokine (PIC) expression in pulmonary tissue after respiratory infection with Pasteurella haemolytica. Cattle were infected with P. haemolytica via fiberoptic deposition of organisms into the posterior part of the right cranial lung lobe. Animals were euthanized at 2 or 4 h postinoculation (p.i.), and tissues were collected to assess PIC gene expression using antisense RNA probes specific for bovine interleukin-1α (IL-1α), IL-1β, IL-6, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α) along with the β-actin (β-Act) housekeeping gene. Expression of PIC was induced at 2 h p.i. in P. haemolytica-infected cattle and continued to 4 h p.i. At 2 h p.i., induction of gene expression and increase of cells that expressed PIC were observed both in CD18+ and CD18− cattle after inoculation of P. haemolytica. The induction of gene expression with P. haemolytica inoculation was more prominent in CD18− cattle than in CD18+ cattle by comparison to pyrogen-free saline (PFS)-inoculated control animals. At 4 h p.i., however, the induction of PIC, especially IL-1α, IL-6, and IFN-γ, in the lungs of CD18+ cattle inoculated with P. haemolytica was greater than that in lungs of the CD18− cattle. IFN-γ and TNF-α genes were not increased in P. haemolytica-inoculated CD18− cattle lungs compared to the PFS-inoculated control lungs at 4 h p.i. In PFS-inoculated lungs, we generally observed a higher percentage of cells and higher level of gene expression in the lungs of CD18− cattle than in the lungs of CD18+ cattle, especially at 4 h p.i. The rate of neutrophil infiltration into the lungs of CD18− cattle at

  19. Hematological changes in calves exposed to a mixture of lipopolysaccharide and crude leukotoxin of Pasteurella haemolytica.

    PubMed Central

    Bowersock, T L; Walker, R D; Maddux, J M; Fenner, D; Moore, R N

    1990-01-01

    The purpose of this investigation was to determine if culture supernatants of Pasteurella haemolytica containing crude leukotoxin and lipopolysaccharide (CLCL) causes disseminated intravascular coagulopathy (DIC) when injected into calves. The effect of intraduodenal (ID) exposure followed by a subsequent subcutaneous (SC) inoculation of either heat-treated or untreated CLCL was evaluated. The relative contribution of the crude leukotoxin and lipopolysaccharide (LPS) to the virulence of P. haemolytica was evaluated. One group of calves received an ID inoculation of CLCL followed two weeks later by a SC inoculation of CLCL; one group received an ID inoculation of tissue culture medium followed two weeks later by a SC inoculation of CLCL; and a third group received an ID inoculation of CLCL followed two weeks later by a SC inoculation of heat-treated CLCL. Hematological parameters used to evaluate DIC included white cell count, platelet count, neutrophil number, fibrinogen, fibrin degradation products, one stage prothrombin time (OSPT), activated partial thromboplastin time, body temperature and clinical signs. Each parameter was measured in calves at 0, 2, 4, 6, 12 and 24 h following the SC inoculation of CLCL. Each group had significant changes over time in all parameters except body temperature. Calves that received a SC inoculation of heat-treated CLCL had smaller changes in all parameters except OSPT compared to the other groups. Results suggest that the LPS and leukotoxin of P. haemolytica exert additive effects on the coagulation cascade and number of peripheral leukocytes, and that the ID inoculation of CLCL does not affect the response of calves to a SC inoculation of toxin. PMID:2249175

  20. Isolation of an ovine pulmonary surfactant-associated anionic peptide bactericidal for Pasteurella haemolytica.

    PubMed

    Brogden, K A; De Lucca, A J; Bland, J; Elliott, S

    1996-01-09

    Ovine pulmonary surfactant is bactericidal for Pasteurella haemolytica when surfactant and bacteria mixtures are incubated with normal ovine serum. To isolate this component, surfactant (1 mg/ml) was centrifuged at 100,000 x gav, and the supernatant was fractionated by HPLC. Fractions were eluted with acetonitrile (10-100%)/0.1% trifluoracetic acid and tested for bactericidal activity. Amino acid and sequence analysis of three bactericidal fractions showed that fraction 2 contained H-GDDDDDD-OH, fraction 3 contained H-DDDDDDD-OH, and fraction 6 contained H-GADDDDD-OH. Peptides in 0.14 M NaCl/10 microM ZnCl2 (zinc saline solution) induced killing of P. haemolytica and other bacteria comparable to defensins and beta-defensins [minimal bactericidal concentration (MBC)50 range, 0.01-0.06 mM] but not in 0.14 M NaCl/10 mM sodium phosphate buffer, pH 7.2/0.5 mM CaCl2/0.15 mM MgCl2 (MBC50 range, 2.8-11.5 mM). Bactericidal activity resided in the core aspartate hexapeptide homopolymeric region, and MBC50 values of aspartate dipeptide-to-heptapeptide homopolymers were inversely proportional to the number of aspartate residues in the peptide. P. haemolytica incubated with H-DDDDDD-OH in zinc saline solution was killed within 30 min. Ultrastructurally, cells contained flocculated intracellular constituents. In contrast to cationic defensins and beta-defensins, surfactant-associated anionic peptides are smaller in size, opposite in charge, and are bactericidal in zinc saline solution. They are members of another class of peptide antibiotics containing aspartate, which when present in pulmonary secretions may help clear bacteria as a part of the innate pulmonary defense system.

  1. Isolation of an ovine pulmonary surfactant-associated anionic peptide bactericidal for Pasteurella haemolytica.

    PubMed Central

    Brogden, K A; De Lucca, A J; Bland, J; Elliott, S

    1996-01-01

    Ovine pulmonary surfactant is bactericidal for Pasteurella haemolytica when surfactant and bacteria mixtures are incubated with normal ovine serum. To isolate this component, surfactant (1 mg/ml) was centrifuged at 100,000 x gav, and the supernatant was fractionated by HPLC. Fractions were eluted with acetonitrile (10-100%)/0.1% trifluoracetic acid and tested for bactericidal activity. Amino acid and sequence analysis of three bactericidal fractions showed that fraction 2 contained H-GDDDDDD-OH, fraction 3 contained H-DDDDDDD-OH, and fraction 6 contained H-GADDDDD-OH. Peptides in 0.14 M NaCl/10 microM ZnCl2 (zinc saline solution) induced killing of P. haemolytica and other bacteria comparable to defensins and beta-defensins [minimal bactericidal concentration (MBC)50 range, 0.01-0.06 mM] but not in 0.14 M NaCl/10 mM sodium phosphate buffer, pH 7.2/0.5 mM CaCl2/0.15 mM MgCl2 (MBC50 range, 2.8-11.5 mM). Bactericidal activity resided in the core aspartate hexapeptide homopolymeric region, and MBC50 values of aspartate dipeptide-to-heptapeptide homopolymers were inversely proportional to the number of aspartate residues in the peptide. P. haemolytica incubated with H-DDDDDD-OH in zinc saline solution was killed within 30 min. Ultrastructurally, cells contained flocculated intracellular constituents. In contrast to cationic defensins and beta-defensins, surfactant-associated anionic peptides are smaller in size, opposite in charge, and are bactericidal in zinc saline solution. They are members of another class of peptide antibiotics containing aspartate, which when present in pulmonary secretions may help clear bacteria as a part of the innate pulmonary defense system. PMID:8552650

  2. Pulmonary lesions induced by Pasteurella haemolytica in neutrophil sufficient and neutrophil deficient calves.

    PubMed Central

    Breider, M A; Walker, R D; Hopkins, F M; Schultz, T W; Bowersock, T L

    1988-01-01

    The role of neutrophils in the development of peracute lung lesions of bovine pneumonic pasteurellosis was investigated. Eight calves were divided into two groups of four calves each. Group I was treated with intravenous phosphate-buffered saline and served as the neutrophil sufficient calves. Group II was treated with intravenous hydroxyurea which produced a state of neutropenia. When peripheral blood neutrophil numbers dropped below 300 cells/microL in group II, all calves were challenged with an intrabronchial bolus of Pasteurella haemolytica in the log phase of growth. An acute inflammatory process occurred in both groups of calves indicated by a rise in body temperature. While pulmonary lesions occurred in both groups by six hours postinoculation, they varied in pathological characteristics. Pulmonary lesions in the neutrophil sufficient calves consisted of fibrinopurulent alveolitis-bronchiolitis with associated alveolar septal necrosis, interlobular edema, and intravascular thrombi. The neutrophil deficient calves had extensive intra-alveolar edema, interlobular edema, intraalveolar hemorrhage, atelectasis, and focal areas of alveolar septal necrosis. These results show that P. haemolytica can induce severe pulmonary tissue damage through both neutrophil dependent and neutrophil independent mechanisms. Images Fig. 1. Fig. 2. PMID:3370555

  3. Plane of nutrition during the preweaned period influences the pathophysiological responses to a combined intranasal bovine herpesvirus-1 and intratracheal Mannheimia haemolytica challenge in post-weaned Holstein calves

    USDA-ARS?s Scientific Manuscript database

    The objective was to determine whether previous plane of milk replacer nutrition (PON) influences the pathophysiological responses to a combined viral-bacterial respiratory challenge. Thirty Holstein calves (1 day of age) were assigned to treatments in a 2 x 3 factorial arrangement with preweaned PO...

  4. Metabolic engineering of Mannheimia succiniciproducens for succinic acid production based on elementary mode analysis with clustering.

    PubMed

    Kim, Won Jun; Ahn, Jung Ho; Kim, Hyun Uk; Kim, Tae Yong; Lee, Sang Yup

    2017-02-01

    Mannheimia succiniciproducens, a capnophilic gram-negative rumen bacterium, has been employed for the efficient production of succinic acid. Although M. succiniciproducens metabolism was previously studied using a genome-scale metabolic model, more metabolic characteristics are to be understood. To this end, elementary mode analysis accompanied with clustering ('EMC' analysis) is used to gain further insights on metabolic characteristics of M. succiniciproducens allowing efficient succinic acid production. Elementary modes (EMs) generated from the central carbon metabolic network of M. succiniciproducens are clustered to systematically analyze succinic acid production routes. Based on the results of EMC analysis, zwf gene is identified as a novel overexpression target for the improved succinic acid production. This gene is overexpressed in a previously constructed succinic acid-overproducing M. succiniciproducens LPK7 strain. Heterologous NADPH-dependent mdh is later intuitively selected for overexpression to synergistically improve succinic acid production by utilizing abundant NADPH pool mediated by the overexpressed zwf. The LPK7 strains co-expressing mdh alone and both zwf and mdh genes are subjected to fed-batch fermentation to better examine their succinic acid production performances. Strategies of EMC analysis will be useful for further metabolic engineering of M. succiniciproducens and other microorganisms to improve production of succinic acid and other chemicals of interest. Copyright © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Iron acquisition in Pasteurella haemolytica: expression and identification of a bovine-specific transferrin receptor.

    PubMed Central

    Ogunnariwo, J A; Schryvers, A B

    1990-01-01

    Seven type 1 field isolates of Pasteurella haemolytica were screened for their ability to use different transferrins as a source of iron for growth. All seven strains were capable of using bovine but not human, porcine, avian, or equine transferrin. A screening assay failed to detect siderophore production in any of the strains tested. Iron-deficient cells from these strains expressed a binding activity, specific for bovine transferrin, that was regulated by the level of iron in the medium. Inhibition of expression by translation and transcription inhibitors suggested that iron regulation was occurring at the gene level. Affinity isolation of receptor proteins from all seven strains with biotinylated bovine transferrin identified a 100-kilodalton iron-regulated outer membrane protein as the bovine transferrin receptor. Iron-regulated outer membrane proteins of 71 and 77 kilodaltons were isolated along with the 100-kilodalton protein when less stringent washing procedures were employed in the affinity isolation procedure. Images PMID:2365453

  6. Simple visual assay for determination of Pasteurella haemolytica cytotoxin neutralizing antibody titers in cattle sera.

    PubMed Central

    Gentry, M J; Confer, A W; Kreps, J A

    1985-01-01

    A simple visual assay is described for determining the capacity of bovine serum to neutralize the cytotoxin produced by Pasteurella haemolytica serotype 1. The test was reproducible from day to day with different target cell populations and cytotoxin preparations. Cytotoxin neutralization titers obtained by the visual assay were comparable to those determined by the trypan blue exclusion and 51Cr-release methods. The visual assay was used to measure neutralization titers of bovine sera obtained from vaccination experiments and fractions of purified serum obtained by gel filtration. The major advantages of the visual assay over other assays are that it is rapid, inexpensive, and does not use radioisotopes. It also does not require specialized equipment, making it adaptable to most laboratories. Images PMID:3905853

  7. The effect of the intra-mammary inoculation of lactating ewes with Pasteurella haemolytica isolates from different sources.

    PubMed

    Watkins, G H; Jones, J E

    1992-01-01

    Lactating Welsh Mountain ewes were inoculated, 3 weeks after lambing, with between 1000 and 10,000 colony forming units of a number of isolates of Pasteurella haemolytica. Isolates from severe, acute mastitis in a ewe, from ovine and bovine pneumonic lesions and from the nasal cavity of healthy lambs, all gave rise to severe, acute mastitis that was clinically indistinguishable from that seen naturally. Two isolates from the milk of ewes with subclinical mastitis did not cause clinical disease after inoculation and, in most ewes, were immediately eliminated. These results suggest that a variety of strains of P. haemolytica are capable of causing severe mastitis in sheep, regardless of their origin, and that there are strains of lower pathogenicity for the mammary gland which are not capable of causing clinical mastitis.

  8. Use of DNA analysis of Pasteurella haemolytica biotype T isolates to monitor transmission in bighorn sheep (Ovis canadensis canadensis).

    PubMed Central

    Jaworski, M D; Ward, A C; Hunter, D L; Wesley, I V

    1993-01-01

    Pneumonia has been identified as a major cause of poor lamb survival in indigenous herds of Rocky Mountain bighorn sheep (Ovis canadensis canadensis) in central Idaho. Pasteurella haemolytica was isolated from five adult Rocky Mountain bighorn ewes captured from a free-ranging herd in central Idaho. The lambs from two of these ewes delivered by cesarean section were free of P. haemolytica until 40 days of age and after repeated contact with their dams. The lambs subsequently developed signs of pneumonia, and P. haemolytica was isolated from nasal, pharyngeal, and transtracheal wash samples from each lamb. All P. haemolytica biotype T isolates from the ewes and lambs, as well as those from a 9-month-old lamb of the same herd from which samples for culture were obtained 2 years earlier, were subjected to HaeIII restriction enzyme analysis (REA) and ribotyping. Two ribotypes and seven REA patterns were visually distinguishable by these procedures. Similarity coefficients (SAB) of 0.09 to 0.95 were calculated for the seven REA patterns. The REA patterns of the isolates from the lambs were identical (SAB = 1.0). The isolates from the lambs also had SAB values of 1.0, which was indicative of identity with one of the seven isolates cultured from the ewes at the time of capture and with the organism isolated from the 9-month-old lamb. These procedures have the discriminatory capabilities necessary to monitor the transmission of specific strains of bacteria within and between animal populations. Images PMID:8385150

  9. Recovery of succinic acid produced by fermentation of a metabolically engineered Mannheimia succiniciproducens strain.

    PubMed

    Song, Hyohak; Huh, Yun Suk; Lee, Sang Yup; Hong, Won Hi; Hong, Yeon Ki

    2007-12-01

    There have recently been much advances in the production of succinic acid, an important four-carbon dicarboxylic acid for many industrial applications, by fermentation of several natural and engineered bacterial strains. Mannheimia succiniciproducens MBEL55E isolated from bovine rumen is able to produce succinic acid with high efficiency, but also produces acetic, formic and lactic acids just like other anaerobic succinic acid producers. We recently reported the development of an engineered M. succiniciproducens LPK7 strain which produces succinic acid as a major fermentation product while producing much reduced by-products. Having an improved succinic acid producer developed, it is equally important to develop a cost-effective downstream process for the recovery of succinic acid. In this paper, we report the development of a simpler and more efficient method for the recovery of succinic acid. For the recovery of succinic acid from the fermentation broth of LPK7 strain, a simple process composed of a single reactive extraction, vacuum distillation, and crystallization yielded highly purified succinic acid (greater than 99.5% purity, wt%) with a high yield of 67.05wt%. When the same recovery process or even multiple reactive extraction steps were applied to the fermentation broth of MBEL55E, lower purity and yield of succinic acid were obtained. These results suggest that succinic acid can be purified in a cost-effective manner by using the fermentation broth of engineered LPK7 strain, showing the importance of integrating the strain development, fermentation and downstream process for optimizing the whole processes for succinic acid production.

  10. Effects of modified Cary and Blair medium on recovery of nonhemolytic Pasteurella haemolytica from Rocky Mountain bighorn sheep (Ovis canadensis canadensis) pharyngeal swabs.

    PubMed

    Wild, M A; Miller, M W

    1994-01-01

    Modified Cary and Blair transport medium (MCB) was evaluated for recovery of Pasteurella spp. from pharyngeal swabs of healthy Rocky Mountain bighorn sheep (Ovis canadensis canadensis). In experiment one, three pharyngeal swabs were collected from each of 25 bighorns. Pasteurella haemolytica was recovered from 21 of 25 swabs tested almost immediately and from 16 of 25 swabs held in MCB medium at about 22 C for 24 hr before testing (P > 0.10). Recovery of P. haemolytica decreased (P < 0.005) to 1 of 25 when swabs were held in MCB medium at about 22 C for 48 hr before testing. In experiment two, four pharyngeal swabs were collected from each of ten bighorns and held in MCB medium at about 5 C for < or = 5, 24, 48, or 72 hr prior to testing. Recovery was unaffected by storage at 5 C; P. haemolytica was isolated from all 40 of these samples. All Pasteurella spp. isolates were nonhemolytic P. haemolytica. In experiment one, most isolates were serotype 4; in experiment two, serotype 3 was most common. We propose that MCB medium is effective for transporting bighorn sheep pharyngeal swabs for P. haemolytica screening because it imposes minimal or no effect on recovery when held < or = 24 hr at 22 C or < or = 72 hr at 5 C.

  11. Pneumonia in Calves Produced with Aerosols of Bovine Herpesvirus 1 and Pasteurella haemolytica

    PubMed Central

    Jericho, K. W. F.; Langford, E. V.

    1978-01-01

    In each of 11 experiments, four calves were exposed first to an aerosol of bovine herpesvirus 1 (BHV1, virus of infectious bovine rhinotracheitis) and second to an aerosol of Pasteurella haemolytica. The interval between aerosols was three to five days. In two other experiments, calves were exposed only to a bacterial aerosol. Climate was controlled for all experiments from the day of viral exposure and for eight of the experiments it was also controlled for four to six days before the first aerosol. The concentration of infectious doses of virus in the aerosols and the number of bacteria in the aerosols of each calf were determined. Macroscopically recognizable rhinitis, tonsillitis, laryngitis, tracheitis and pneumonia of lobar distribution in 42 lobes from 11 calves were seen in five experiments in which bacterial aerosol followed the viral aerosol by at least four days. One calf died with marked respiratory disease in each of four experiments within four days of exposure to the bacterial aerosol. Production of pneumonia was dependent on an interval between aerosols of at least four days but not on the condition of controlled climate on the environmental chamber either before or after the viral aerosol nor on the period of habituation allowed calves of some experiments. ImagesFig. 1.Fig. 2.Fig. 3. PMID:210912

  12. Thermomonas haemolytica gen. nov., sp. nov., a gamma-proteobacterium from kaolin slurry.

    PubMed

    Busse, H J; Kämpfer, P; Moore, E R B; Nuutinen, J; Tsitko, I V; Denner, E B M; Vauterin, L; Valens, M; Rosselló-Mora, R; Salkinoja-Salonen, M S

    2002-03-01

    Four aerobic, gram-negative bacterial strains isolated from kaolin slurry used in the production of paper were subjected to a polyphasic analysis and characterization to determine their taxonomic position. Analysis of the 16S rDNA sequences of the four strains revealed that they represent a new lineage within the gamma-Proteobacteria, related to the genera Xanthomonas, Pseudoxanthomonas, Stenotrophomonas, Luteimonas, Xylella and Rhodanobacter. Analysis of the quinone system, the polyamines, the fatty acids and the polar lipids revealed a combination of characteristics that is unique and not described for the phylogenetic relatives. The four strains contain a ubiquinone Q-8, spermidine as the major polyamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine as the predominant polar lipids, and a fatty acid profile with predominantly iso-branched fatty acids. The G+C content of the genomic DNA was determined to be within the narrow range 67.1-68.7 mol%. Determination of DNA relatedness, as well as riboprint band patterns and amplified fragment length polymorphism profiles, clearly demonstrated that the four strains are members of a single species. Antibiotic-susceptibility patterns were identical for the four strains. Although showing a high degree of similarites in physiological and biochemical patterns, each of the four strains could be distinguished from the others on the basis of a few biochemical characteristics. On the basis of the estimates of phylogenetic relationships derived from the 16S rDNA sequence analyses, the observed chemotaxonomic characteristics and other phenotypic traits, a new genus, Thermomonas gen. nov., and species, Thermomonas haemolytica sp. nov., are proposed for the strains A50-7-3T (= DSM 13605T = LMG 19653T), B 50-7-1 (= DSM 13598 = LMG 19655), D50-7-1 (= DSM 13610 = LMG 19656) and B50-8-1 (= DSM 13599 = LMG 19654), with strain A50-7-3T as the type strain.

  13. Tilmicosin Induces Apoptosis in Bovine Peripheral Neutrophils in the Presence or in the Absence of Pasteurella haemolytica and Promotes Neutrophil Phagocytosis by Macrophages

    PubMed Central

    Chin, Alex C.; Lee, Wilson D.; Murrin, Katherine A.; Morck, Douglas W.; Merrill, John K.; Dick, Paul; Buret, Andre G.

    2000-01-01

    Pathogen virulence factors and inflammation are responsible for tissue injury associated with respiratory failure in bacterial pneumonia, as seen in the bovine lung infected with Pasteurella haemolytica. Tilmicosin is a macrolide antibiotic used for the treatment of bovine bacterial pneumonia. Recent evidence suggests that tilmicosin-induced neutrophil apoptosis may have anti-inflammatory effects. Using bovine leukocytes, we sought to define whether live P. haemolytica affected tilmicosin-induced neutrophil apoptosis, assessed the proapoptotic effects of tilmicosin in comparison with other drugs, and characterized its impact on phagocytic uptake of neutrophils by macrophages. Induction of apoptosis in the presence or absence of P. haemolytica was assessed by using an enzyme-linked immunosorbent assay for apoptotic nucleosomes. In addition, fluorescent annexin-V staining identified externalized phosphatidylserine in neutrophils treated with tilmicosin, penicillin, ceftiofur, oxytetracycline, or dexamethasone. Neutrophil membrane integrity was assessed by using propidium iodide and trypan blue exclusion. As phagocytic clearance of apoptotic neutrophils by macrophages contributes to the resolution of inflammation, phagocytosis of tilmicosin-treated neutrophils by esterase-positive cultured bovine macrophages was assessed with light microscopy and transmission electron microscopy. Unlike bovine neutrophils treated with penicillin, ceftiofur, oxytetracycline, or dexamethasone, neutrophils exposed to tilmicosin became apoptotic, regardless of the presence or absence of P. haemolytica. Tilmicosin-treated apoptotic neutrophils were phagocytosed at a significantly greater rate by bovine macrophages than were control neutrophils. In conclusion, tilmicosin-induced neutrophil apoptosis occurs regardless of the presence or absence of live P. haemolytica, exhibits at least some degree of drug specificity, and promotes phagocytic clearance of the dying inflammatory cells. PMID

  14. Capsular polysaccharide vaccine for Group B Neisseria meningitidis, Escherichia coli K1, and Pasteurella haemolytica A2.

    PubMed

    Robbins, John B; Schneerson, Rachel; Xie, Guilin; Hanson, Lars Å; Åke-Hanson, Lars; Miller, Mark A

    2011-11-01

    We reviewed the literature that is the basis for our proposal that (2→8)-α-Neu5Ac conjugates will be safe and effective vaccines for Group B meningococci (GBMs), Escherichia coli K1, and Pasteurella haemolytica A2. Although (2→8)-α-Neu5Ac is a virulence factor and a protective antigen of these three pathogens, it is also a component of normal tissues (neural cell adhesion molecule). Natural, anti-(2→8)-α-Neu5Ac present in most adults, vaccine-induced antibodies, and even high levels of spontaneously appearing monoclonal anti-(2→8)-α-Neu5Ac did not cause autoimmunity. Although it is not possible to prove a null hypothesis, there are no epidemiologic, serologic, immunologic, or clinical data to indicate that (2→8)-α-Neu5Ac antibodies will induce pathology or an autoimmune disease. No increased pathology caused by these antibodies was found, even in neonates and infants of mothers recovered from GBM meningitis. The lack of pathology mediated by anti-(2→8)-α-Neu5Ac may be explained by different presentations of (2→8)-α-Neu5Ac on bacterial and mammalian cells and by the unusual physicochemical properties of anti-(2→8)-α-Neu5Ac. Based on clinical and experimental data collected over 30 y and because (2→8)-α-Neu5Ac is an essential virulence factor and a protective antigen for GBM, E. coli K1, and P. haemolytica A2, protein conjugates of it are easy to prepare using inexpensive and plentiful ingredients, and they would be compatible with routinely administered infant vaccines, clinical studies of these conjugates should proceed.

  15. Characterization of the Arc two-component signal transduction system of the capnophilic rumen bacterium Mannheimia succiniciproducens.

    PubMed

    Jung, Won Seok; Jung, Young Ryul; Oh, Doo-Byoung; Kang, Hyun Ah; Lee, Sang Yup; Chavez-Canales, Maria; Georgellis, Dimitris; Kwon, Ohsuk

    2008-07-01

    The ArcB/A two-component signal transduction system of Escherichia coli modulates the expression of numerous operons in response to redox conditions of growth. We demonstrate that the putative arcA and arcB genes of Mannheimia succiniciproducens MBEL55E, a capnophilic (CO2-loving) rumen bacterium, encode functional proteins that specify a two-component system. The Arc proteins of the two bacterial species sufficiently resemble each other that they can participate in heterologous transphosphorylation in vitro, and the arcA and arcB genes of M. succiniciproducens confer toluidine blue resistance to E. coli arcA and arcB mutants. However, neither the quinone analogs (ubiquinone 0 and menadione) nor the cytosolic effectors (d-lactate, acetate, and pyruvate) affect the net phosphorylation of M. succiniciproducens ArcB. Our results indicate that different types of signaling molecules and distinct modes of kinase regulation are used by the ArcB proteins of E. coli and M. succiniciproducens.

  16. Complete closed genome sequences of three Bibersteinia trehalosi nasopharyngeal isolates from cattle with shipping fever

    USDA-ARS?s Scientific Manuscript database

    Bibersteinia trehalosi is a respiratory pathogen affecting cattle and related ruminants worldwide. B. trehalosi is closely related to Mannheimia haemolytica, and is often associated with bovine respiratory disease complex (BRDC), a polymicrobial multifactorial disease. We present three complete clos...

  17. 21 CFR 522.2460 - Tildipirosin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni in beef and non-lactating dairy cattle; and for the control of respiratory disease in beef and non...

  18. Observations on macrolide resistance and susceptibility testing performance in field isolates collected from clinical bovine respiratory disease cases

    USDA-ARS?s Scientific Manuscript database

    The objectives of this study were; first, to describe gamithromycin susceptibility of Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni isolated from cattle diagnosed with bovine respiratory disease (BRD) and previously treated with either gamithromycin for control of BRD (mass me...

  19. Comparison of the diagnostic performance of bacterial culture of nasopharyngeal swab and bronchoalveolar lavage fluid samples obtained from calves with bovine respiratory disease

    USDA-ARS?s Scientific Manuscript database

    Objective: Examine the culture results, gamithromycin susceptibility, predictive values, and agreement of pooled bilateral nasopharyngeal swabs (NPS) and bronchoalveolar lavages (BAL) for identification of Mannheimia haemolytica genotypes, Pasteurella multocida, and Histophilus somni in calves treat...

  20. 21 CFR 522.2630 - Tulathromycin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. For the control of respiratory disease in cattle at high risk of... the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, P...

  1. 21 CFR 522.2630 - Tulathromycin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. For the control of respiratory disease in cattle at high risk of... the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, P...

  2. 21 CFR 522.2630 - Tulathromycin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. For the control of respiratory disease in cattle at high risk of... the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, P...

  3. 21 CFR 522.955 - Florfenicol.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida... injection. (2) Indications for use. For control of respiratory disease in cattle at high risk of developing...

  4. 21 CFR 522.2630 - Tulathromycin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. For the control of respiratory disease in cattle at high risk of... the treatment of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, P...

  5. Purification, characterization and immunological properties of the capsular polysaccharide of Pasteurella haemolytica serotype T15: its identity with the K62 (K2ab) capsular polysaccharide of Escherichia coli and the capsular polysaccharide of Neisseria meningitidis serogroup H.

    PubMed

    Adlam, C; Knights, J M; Mugridge, A; Lindon, J C; Williams, J M; Beesley, J E

    1985-08-01

    Capsular polysaccharide from two strains of Pasteurella haemolytica serotype T15 was purified and characterized by chemical analysis and NMR spectroscopy. The polymer, a teichoic acid, proved to be very similar in structure to the capsular polysaccharide of P. haemolytica serotype T4 and identical to the previously described K62 (K2ab) capsular polysaccharide of Escherichia coli, and the capsular polysaccharide of Neisseria meningitidis serotype H, i.e. ----(2-glycerol-3)----(phosphate)----(4-alpha-D-galactopyranose -1)---- with partial O-acetylation on the galactose residues. Electron microscopy with Protein A-gold labelled antisera showed that the polysaccharide was peripherally located on the surface of all three organisms. Chemical removal of O-acetyl groups from the polysaccharide yielded a structure identical to that previously described for E. coli K2 (K2a). Both O-acetylated and de-O-acetylated P. haemolytica T15 polymers, when absorbed on to sheep erythrocytes in passive haemagglutination assays, yielded identical antibody titres with sera raised against P. haemolytica T15, E. coli K2 or N. meningitidis H whole cells. De-O-acetylation of the Pasteurella polysaccharide influenced its precipitability with immune sera, but this could not be related to the absence of O-acetyl groups because the non-acetylated E. coli K2 polymer readily precipitated with a line of 'identity' with the acetylated P. haemolytica T15 polymer.

  6. In silico analysis of the effects of H2 and CO2 on the metabolism of a capnophilic bacterium Mannheimia succiniciproducens.

    PubMed

    Kim, Tae Yong; Kim, Hyun Uk; Song, Hyohak; Lee, Sang Yup

    2009-11-01

    This study presents an in-depth study on the physiological behavior of Mannheimia succiniciproducens, a capnophilic bacterium and an efficient succinic acid producer, under varying gas conditions as H(2) and CO(2) play important roles in the production of succinic acid. Constraints-based flux analysis of the genome-scale metabolic model of M. succiniciproducens was performed to estimate the production patterns of several organic acids in response to varying H(2), CO(2), and glucose uptake rates. Results from controlled cultivations performed previously and constraints-based flux analyses of M. succiniciproducens in this study revealed that there is an optimal range of CO(2) level in the medium for enhancing cell growth and succinic acid production at a given glucose uptake rate. Furthermore, the uptake rates of H(2) and CO(2) from the medium have a direct relationship with each other, significantly influencing the rates of cell growth and succinic acid production. Predictions made in this study quantitatively describe the physiological changes of the cell in response to varying H(2), CO(2), and glucose uptake rates, which consequently allow us to identify the feasible physiological states of the cell with respect to cell growth rate and succinic acid production rate.

  7. Serological titers to bovine herpesvirus 1, bovine viral diarrhea virus, parainfluenza 3 virus, bovine respiratory syncytial virus and Pasteurella haemolytica in feedlot calves with respiratory disease: associations with bacteriological and pulmonary cytological variables.

    PubMed Central

    Allen, J W; Viel, L; Bateman, K G; Nagy, E; Røsendal, S; Shewen, P E

    1992-01-01

    Acute and convalescent serum samples were taken from 59 calves with signs of respiratory disease (cases) and 60 clinically normal animals (controls) during their first month in the feedlot. Sera were analyzed for antibodies to bovine parainfluenza 3 (PI3) virus by hemagglutination inhibition, to bovine viral diarrhea (BVD) virus, bovine respiratory syncytial (BRS) virus and bovine herpesvirus 1 (BHV1) by virus neutralization, and to Pasteurella haemolytica by indirect agglutination (PhIA) and cytotoxin neutralization (PhCN) tests. There was minimal evidence of serological activity to BHV1. Serological activity to the other agents occurred commonly and the prevalence of acute titers and their mean values was similar in case and control groups. Mean convalescent PI3 and P. haemolytica (PhIA) titers were higher in controls than cases (p < 0.01) but, otherwise, convalescent titers did not differ between groups. The incidence of seroconversion was similar in both groups for all agents except for PI3 virus which was more frequent in controls than cases (p < 0.0001). There was a positive association between PhIA and CN seroconversion and isolation of P. haemolytica from bronchoalveolar lavage (BAL) fluid (p < 0.1). The measure of agreement (kappa) between seroconversion with the P. haemolytica PhIA and PhCN tests was 0.51. Bacteriological and cytological evaluations of the respiratory tract were made using BAL. No associations were evident between serological titers and pulmonary cytology. A multivariate logistic analysis was used to evaluate associations between disease status and serological, bacteriological and cytological data. Cases were positively associated with the presence of neutrophils and Pasteurella multocida in BAL fluid and negatively associated with PI3 virus and PhIA seroconversion. PMID:1335831

  8. Responses to aggregating agents after cleavage of GPIb of human platelets by the O-sialoglycoprotein endoprotease from Pasteurella haemolytica- potential surrogates for Bernard-Soulier platelets?

    PubMed

    Kinlough-Rathbone, R L; Perry, D W; Rand, M L; Packham, M A

    2000-07-15

    Most proteolytic enzymes that cleave glycoprotein lb (GPlb) also cleave other glycoproteins or receptors on the surface of platelets. We have used an O-sialoglycoprotein endoprotease from Pasteurella haemolytica that selectively cleaves the heavily O-glycosylated GPlb, but does not cleave N-linked glycoproteins or unglycosylated proteins. Isolated, [14C]serotonin-labeled platelets in Tyrode-albumin solution were incubated with 10 microg/mL endoprotease for 60 minutes at 37 degrees C. These platelets did not release [14C]serotonin, had no detectable GPIb, and were unresponsive to ristocetin/von Willebrand factor. Compared with control platelets, aggregation and release of [14C]serotonin by the endoprotease-pretreated platelets were inhibited in response to low concentrations of thrombin, SFLLRN (the PAR-1-activating peptide), collagen, and U46619 (a thromboxane A(2) mimetic); aggregates were smaller in size. The presence of fibrinogen overcame the inhibition of responses induced by SFLLRN, collagen, and U46619. With fibrinogen, primary ADP-induced aggregation was scarcely affected by pretreatment with the endoprotease. Thus, the PAR-1 receptor for thrombin, and receptors for collagen, thromboxane A(2), fibrinogen (GPIIb/IIIa), and ADP appear to function normally on the endoprotease-pretreated platelets. Since only GPIb is cleaved by the endoprotease, these platelets seem to provide potential surrogates for Bernard-Soulier syndrome platelets for further studies of platelet functions in this condition.

  9. 21 CFR 522.2460 - Tildipirosin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.2460... respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus...

  10. MHC class II DR allelic diversity in bighorn sheep

    USDA-ARS?s Scientific Manuscript database

    We hypothesized that decreased diversity and/or unique polymorphisms in MHC class II alleles of bighorn sheep (BHS, Ovis canadensis) are responsible for lower titer of antibodies against Mannheimia haemolytica leukotoxin, in comparison to domestic sheep (DS, Ovis aries). To test this hypothesis, DRA...

  11. 21 CFR 522.2630 - Tulathromycin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... use. For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, and Mycoplasma bovis. For the control of respiratory disease in... the neck. (ii) Indications for use. For the treatment of swine respiratory disease (SRD) associated...

  12. 21 CFR 522.1660b - Oxytetracycline solution, 300 milligrams/milliliter.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... respiratory disease in cattle at high risk of developing BRD associated with Mannheimia (Pasteurella) haemolytica. (ii) Limitations. Treatment should be continued 24 to 48 hours following remission of disease... advanced cases of other indicated diseases. (C) 9 mg/lb BW intramuscularly or subcutaneously as single...

  13. 21 CFR 522.1660b - Oxytetracycline solution, 300 milligrams/milliliter.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... respiratory disease in cattle at high risk of developing BRD associated with Mannheimia (Pasteurella) haemolytica. (ii) Limitations. Treatment should be continued 24 to 48 hours following remission of disease... advanced cases of other indicated diseases. (C) 9 mg/lb BW intramuscularly or subcutaneously as single...

  14. 21 CFR 522.2471 - Tilmicosin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...) Indications for use. For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. For the control of respiratory disease in cattle at... a single subcutaneous injection. (ii) Indications for use. For the treatment of ovine respiratory...

  15. 21 CFR 522.812 - Enrofloxacin.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... therapy: For treatment of bovine respiratory disease (BRD), administer 7.5 to 12.5 mg/kg of body weight (3... respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni... of swine respiratory disease (SRD) associated with Actinobacillus pleuropneumoniae, Pasteurella...

  16. 21 CFR 522.2471 - Tilmicosin.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ...) Indications for use. For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. For the control of respiratory disease in cattle at... a single subcutaneous injection. (ii) Indications for use. For the treatment of ovine respiratory...

  17. 21 CFR 522.1660b - Oxytetracycline solution, 300 milligrams/milliliter.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... respiratory disease in cattle at high risk of developing BRD associated with Mannheimia (Pasteurella) haemolytica. (ii) Limitations. Treatment should be continued 24 to 48 hours following remission of disease... advanced cases of other indicated diseases. (C) 9 mg/lb BW intramuscularly or subcutaneously as single...

  18. 21 CFR 522.2471 - Tilmicosin.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ...) Indications for use. For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. For the control of respiratory disease in cattle at... a single subcutaneous injection. (ii) Indications for use. For the treatment of ovine respiratory...

  19. 21 CFR 522.2471 - Tilmicosin.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...) Indications for use. For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. For the control of respiratory disease in cattle at... a single subcutaneous injection. (ii) Indications for use. For the treatment of ovine respiratory...

  20. 21 CFR 522.1660b - Oxytetracycline solution, 300 milligrams/milliliter.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... respiratory disease in cattle at high risk of developing BRD associated with Mannheimia (Pasteurella) haemolytica. (ii) Limitations. Treatment should be continued 24 to 48 hours following remission of disease... advanced cases of other indicated diseases. (C) 9 mg/lb BW intramuscularly or subcutaneously as single...

  1. 21 CFR 522.1660b - Oxytetracycline solution, 300 milligrams/milliliter.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... respiratory disease in cattle at high risk of developing BRD associated with Mannheimia (Pasteurella) haemolytica. (ii) Limitations. Treatment should be continued 24 to 48 hours following remission of disease... advanced cases of other indicated diseases. (C) 9 mg/lb BW intramuscularly or subcutaneously as single...

  2. 21 CFR 522.2471 - Tilmicosin.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...) Indications for use. For the treatment of bovine respiratory disease (BRD) associated with Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. For the control of respiratory disease in cattle at... a single subcutaneous injection. (ii) Indications for use. For the treatment of ovine respiratory...

  3. Bighorn sheep pneumonia: Sorting out the cause of a polymicrobial disease

    USDA-ARS?s Scientific Manuscript database

    Pneumonia of bighorn sheep (Ovis canadensis) is a dramatic disease of high morbidity and mortality first described more than 80 years ago. The etiology of the disease has been debated since its initial discovery, and at various times lungworms, Mannheimia haemolytica and other Pasteurellaceae, and M...

  4. Molecular cloning, characterization and in vitro expression of SERPIN B1 of bighorn sheep (Ovis canadensis) and domestic sheep (Ovis aries), and comparison with that of other species

    USDA-ARS?s Scientific Manuscript database

    Mannheimia haemolytica infection results in enhanced PMN-mediated tissue damage in the lungs of bighorn sheep (BHS) compared to that of domestic sheep (DS). SERPIN B1 is an inhibitor of PMN-derived serine proteases. It prevents lung tissue injury by inhibiting the serine proteases released as a resu...

  5. A1C test

    MedlinePlus

    HbA1C test; Glycated hemoglobin test; Glycohemoglobin test; Hemoglobin A1C; Diabetes - A1C; Diabetic - A1C ... gov/pubmed/26696680 . Chernecky CC, Berger BJ. Glycosylated hemoglobin (GHb, glycohemoglobin, glycated hemoglobin, HbA1a, HbA1b, HbA1c - blood. ...

  6. Pathogens of Bovine Respiratory Disease in North American Feedlots Conferring Multidrug Resistance via Integrative Conjugative Elements

    PubMed Central

    Klima, Cassidy L.; Zaheer, Rahat; Cook, Shaun R.; Booker, Calvin W.; Hendrick, Steve

    2014-01-01

    In this study, we determined the prevalence of bovine respiratory disease (BRD)-associated viral and bacterial pathogens in cattle and characterized the genetic profiles, antimicrobial susceptibilities, and nature of antimicrobial resistance determinants in collected bacteria. Nasopharyngeal swab and lung tissue samples from 68 BRD mortalities in Alberta, Canada (n = 42), Texas (n = 6), and Nebraska (n = 20) were screened using PCR for bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus, bovine herpesvirus 1, parainfluenza type 3 virus, Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Excepting bovine herpesvirus 1, all agents were detected. M. haemolytica (91%) and BVDV (69%) were the most prevalent, with cooccurrence in 63% of the cattle. Isolates of M. haemolytica (n = 55), P. multocida (n = 8), and H. somni (n = 10) from lungs were also collected. Among M. haemolytica isolates, a clonal subpopulation (n = 8) was obtained from a Nebraskan feedlot. All three bacterial pathogens exhibited a high rate of antimicrobial resistance, with 45% exhibiting resistance to three or more antimicrobials. M. haemolytica (n = 18), P. multocida (n = 3), and H. somni (n = 3) from Texas and Nebraska possessed integrative conjugative elements (ICE) that conferred resistance for up to seven different antimicrobial classes. ICE were shown to be transferred via conjugation from P. multocida to Escherichia coli and from M. haemolytica and H. somni to P. multocida. ICE-mediated multidrug-resistant profiles of bacterial BRD pathogens could be a major detriment to many of the therapeutic antimicrobial strategies currently used to control BRD. PMID:24478472

  7. Pathogens of bovine respiratory disease in North American feedlots conferring multidrug resistance via integrative conjugative elements.

    PubMed

    Klima, Cassidy L; Zaheer, Rahat; Cook, Shaun R; Booker, Calvin W; Hendrick, Steve; Alexander, Trevor W; McAllister, Tim A

    2014-02-01

    In this study, we determined the prevalence of bovine respiratory disease (BRD)-associated viral and bacterial pathogens in cattle and characterized the genetic profiles, antimicrobial susceptibilities, and nature of antimicrobial resistance determinants in collected bacteria. Nasopharyngeal swab and lung tissue samples from 68 BRD mortalities in Alberta, Canada (n = 42), Texas (n = 6), and Nebraska (n = 20) were screened using PCR for bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus, bovine herpesvirus 1, parainfluenza type 3 virus, Mycoplasma bovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. Excepting bovine herpesvirus 1, all agents were detected. M. haemolytica (91%) and BVDV (69%) were the most prevalent, with cooccurrence in 63% of the cattle. Isolates of M. haemolytica (n = 55), P. multocida (n = 8), and H. somni (n = 10) from lungs were also collected. Among M. haemolytica isolates, a clonal subpopulation (n = 8) was obtained from a Nebraskan feedlot. All three bacterial pathogens exhibited a high rate of antimicrobial resistance, with 45% exhibiting resistance to three or more antimicrobials. M. haemolytica (n = 18), P. multocida (n = 3), and H. somni (n = 3) from Texas and Nebraska possessed integrative conjugative elements (ICE) that conferred resistance for up to seven different antimicrobial classes. ICE were shown to be transferred via conjugation from P. multocida to Escherichia coli and from M. haemolytica and H. somni to P. multocida. ICE-mediated multidrug-resistant profiles of bacterial BRD pathogens could be a major detriment to many of the therapeutic antimicrobial strategies currently used to control BRD.

  8. A1C Test

    MedlinePlus

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Hemoglobin A1c Share this page: Was this page helpful? Also known as: A1c; HbA1c; Glycohemoglobin; Glycated Hemoglobin; Glycosylated Hemoglobin Formal name: Hemoglobin A1c Related tests: ...

  9. Pharmacokinetics of ceftiofur crystalline-free acid following subcutaneous administration of a single dose to sheep.

    PubMed

    Rivera-Garcia, Sarai; Angelos, John A; Rowe, Joan D; Byrne, Barbara A; Wetzlich, Scott E; Van Liew, Dana B; Tell, Lisa A

    2014-03-01

    To determine the pharmacokinetics of ceftiofur crystalline-free acid (CCFA) following SC administration of a single dose to sheep. 9 healthy adult female Suffolk-crossbred sheep. Each sheep was administered 6.6 mg of CCFA/kg, SC, in the cervical region once. Serial blood samples were collected at predetermined intervals for 14 days. Serum concentration of ceftiofur free-acid equivalents (CFAE) was determined by high-performance liquid chromatography. Pharmacokinetic parameters were determined by compartmental and noncompartmental methods. Pharmacokinetics for CCFA following SC administration in sheep was best described with a 1-compartment model. Mean ± SD area under the concentration-time curve from time 0 to infinity, peak serum concentration, and time to peak serum concentration were 206.6 ± 24.8 μ•h/mL, 2.4 ± 0.5 μg/mL, and 23.1 ± 10.1 h, respectively. Serum CFAE concentrations ≥ 1 μg/mL (the target serum CFAE concentration for treatment of disease caused by Mannheimia haemolytica and Pasteurella multocida) were maintained for 2.6 to 4.9 days. No significant adverse reactions to CCFA administration were observed. Results indicated that adequate therapeutic serum concentrations of CFAE for treatment of disease caused by M haemolytica and P multocida were achieved in sheep following SC administration of a single dose (6.6 mg/kg) of CCFA. Thus, CCFA might be useful for the treatment of common respiratory tract pathogens in sheep.

  10. A1C

    MedlinePlus

    A1C is a blood test for type 2 diabetes and prediabetes. It measures your average blood glucose, or blood sugar, level over the past 3 ... A1C alone or in combination with other diabetes tests to make a diagnosis. They also use the ...

  11. Fusobacterium necrophorum in North American Bighorn Sheep ( Ovis canadensis ) Pneumonia.

    PubMed

    Shanthalingam, Sudarvili; Narayanan, Sanjeevkumar; Batra, Sai Arun; Jegarubee, Bavananthasivam; Srikumaran, Subramaniam

    2016-07-01

    Fusobacterium necrophorum has been detected in pneumonic bighorn sheep (BHS; Ovis canadensis ) lungs, in addition to the aerobic respiratory pathogens Mannheimia haemolytica , Bibersteinia trehalosi , Pasteurella multocida , and Mycoplasma ovipneumoniae . Similar to M. haemolytica , F. necrophorum produces a leukotoxin. Leukotoxin-induced lysis and degranulation of polymorphonuclear leukocytes (PMNs) and macrophages are responsible for acute inflammation and lung tissue damage characteristic of M. haemolytica -caused pneumonia. As one approach in elucidating the role of F. necrophorum in BHS pneumonia, we determined the frequency of the presence of F. necrophorum in archived pneumonic BHS lung tissues, and susceptibility of BHS leukocytes to F. necrophorum leukotoxin. A species-specific PCR assay detected F. necrophorum in 37% of pneumonic BHS lung tissues (total tested n=70). Sequences of PCR amplicons were similar to the less virulent F. necrophorum subsp. funduliforme. Fusobacterium necrophorum leukotoxin exhibited cytotoxicity to BHS PMNs and peripheral blood mononuclear cells. As with the M. haemolytica leukotoxin, F. necrophorum leukotoxin was more toxic to BHS PMNs than domestic sheep PMNs. It is likely that F. necrophorum enters the lungs after M. haemolytica and other aerobic respiratory pathogens enter the lungs and initiate tissue damage, thereby creating a microenvironment that is conducive for anaerobic bacterial growth. In summary, Fusobacterium leukotoxin is highly toxic for BHS leukocytes; however, based on the PCR findings, it is unlikely to play a direct role in the development of BHS pneumonia.

  12. Methodological comparisons for antimicrobial resistance surveillance in feedlot cattle

    PubMed Central

    2013-01-01

    Background The purpose of this study was to objectively compare methodological approaches that might be utilized in designing an antimicrobial resistance (AMR) surveillance program in beef feedlot cattle. Specifically, four separate comparisons were made to investigate their potential impact on estimates for prevalence of AMR. These included investigating potential differences between 2 different susceptibility testing methods (broth microdilution and disc diffusion), between 2 different target bacteria (non-type-specific E. coli [NTSEC] and Mannheimia haemolytica), between 2 strategies for sampling feces (individual samples collected per rectum and pooled samples collected from the pen floor), and between 2 strategies for determining which cattle to sample (cattle that were culture-positive for Mannheimia haemolytica and those that were culture-negative). Results Comparing two susceptibility testing methods demonstrated differences in the likelihood of detecting resistance between automated disk diffusion (BioMIC®) and broth microdilution (Sensititre®) for both E. coli and M. haemolytica. Differences were also detected when comparing resistance between two bacterial organisms within the same cattle; there was a higher likelihood of detecting resistance in E. coli than in M. haemolytica. Differences in resistance prevalence were not detected when using individual animal or composite pen sampling strategies. No differences in resistance prevalences were detected in E. coli recovered from cattle that were culture-positive for M. haemolytica compared to those that were culture-negative, suggesting that sampling strategies which targeted recovery of E. coli from M. haemolytica-positive cattle would not provide biased results. Conclusions We found that for general purposes, the susceptibility test selected for AMR surveillance must be carefully chosen considering the purpose of the surveillance since the ability to detect resistance appears to vary between these tests

  13. A-1 to Constellation

    NASA Technical Reports Server (NTRS)

    2006-01-01

    The A-1 Test Stand at NASA Stennis Space Center near Bay St. Louis, Miss., was the focus of a ceremony held Thursday to transition the storied facility to a new program of work: testing the J-2X engines that will power the agency's next generation spacecraft, Ares I & V. Standing before the historic structure, with a plaque commemorating the change, are (from left) SSC Center Director Richard Gilbrech; NASA Associate Administrator for Exploration Systems Scott Horowitz; and NASA Space Operations Deputy Associate Administrator for Program Integration Michael Hawes. Ares vehicles are the crew and cargo launch vehicles being developed under NASA's Constellation Program.

  14. A-1 to Constellation

    NASA Image and Video Library

    2006-11-09

    The A-1 Test Stand at NASA Stennis Space Center near Bay St. Louis, Miss., was the focus of a ceremony held Thursday to transition the storied facility to a new program of work: testing the J-2X engines that will power the agency's next generation spacecraft, Ares I & V. Standing before the historic structure, with a plaque commemorating the change, are (from left) SSC Center Director Richard Gilbrech; NASA Associate Administrator for Exploration Systems Scott Horowitz; and NASA Space Operations Deputy Associate Administrator for Program Integration Michael Hawes. Ares vehicles are the crew and cargo launch vehicles being developed under NASA's Constellation Program.

  15. Inhibition of Protein Synthesis on the Ribosome by Tildipirosin Compared with Other Veterinary Macrolides

    PubMed Central

    Andersen, Niels Møller; Poehlsgaard, Jacob; Warrass, Ralf

    2012-01-01

    Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC50], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal binding site. PMID:22926570

  16. Inhibition of protein synthesis on the ribosome by tildipirosin compared with other veterinary macrolides.

    PubMed

    Andersen, Niels Møller; Poehlsgaard, Jacob; Warrass, Ralf; Douthwaite, Stephen

    2012-11-01

    Tildipirosin is a 16-membered-ring macrolide developed to treat bacterial pathogens, including Mannheimia haemolytica and Pasteurella multocida, that cause respiratory tract infections in cattle and swine. Here we evaluated the efficacy of tildipirosin at inhibiting protein synthesis on the ribosome (50% inhibitory concentration [IC(50)], 0.23 ± 0.01 μM) and compared it with the established veterinary macrolides tylosin, tilmicosin, and tulathromycin. Mutation and methylation at key rRNA nucleotides revealed differences in the interactions of these macrolides within their common ribosomal binding site.

  17. Mycoplasma alkalescens demonstrated in bronchoalveolar lavage of cattle in Denmark

    PubMed Central

    Kokotovic, Branko; Friis, Niels F; Ahrens, Peter

    2007-01-01

    Mycoplasma alkalescens is an arginine-metabolizing mycoplasma, which has been found in association with mastitis and arthritis in cattle. Routine bacteriological examination of 17 bronchoalveolar lavage samples from calves with pneumonia in a single herd in Denmark, identified M. alkalescens in eight samples. The organism was found as a sole bacterilogical findings in five of the samples as well as in combination with Mannheimia haemolytica, Haemophilus somni and Salmonella Dublin. This is the first report of isolation of M. alkalescens in Denmark. PMID:17204146

  18. Molecular cloning of interleukin-1β, interleukin-8, and tumor necrosis factor-α of bighorn sheep (Ovis canadensis) and comparison with those of other species.

    PubMed

    Herndon, Caroline N; Dassanayake, Rohana P; Foreyt, William J; Srikumaran, Subramaniam

    2010-11-15

    The susceptibility to, and pathology induced by, Mannheimia haemolytica infection in bighorn sheep (BHS) and domestic sheep (DS) are distinctly different. Bighorn sheep are particularly susceptible to pneumonia caused by M. haemolytica, and the pneumonic lesions in infected BHS are more severe than those in DS. The molecular basis for this disparity has not been elucidated. Proinflammatory cytokines have been implicated in the pathogenesis of multiple lung diseases of humans and animals. It is possible that the enhanced pathology observed in the pneumonic lungs of M. haemolytica-infected BHS, in comparison to that of DS, is due to comparatively higher levels of proinflammatory cytokine expression in BHS. As the first step towards elucidating this concept, we have cloned and sequenced the cDNA encoding the cytokines interleukin-1β (IL-1β), interleukin-8 (IL-8), and tumor necrosis factor-α (TNF-α) of BHS. The cDNA of BHS IL-1β, IL-8, and TNF-α consists of 801, 306, and 705 base pairs encoding 266, 101, and 234 amino acids, respectively. The availability of cDNA encoding IL-1β, IL-8, and TNF-α of BHS should facilitate the elucidation of the role of these cytokines in the differential pathology induced by M. haemolytica infection in BHS and DS. Copyright © 2010 Elsevier B.V. All rights reserved.

  19. A-1 Test Stand modifications

    NASA Image and Video Library

    2011-09-14

    Team members check the progress of a liquid nitrogen cold shock test on the A-1 Test Stand at Stennis Space Center on Sept. 15. The cold shock test is used to confirm the test stand's support system can withstand test conditions, when super-cold rocket engine propellant is piped. The A-1 Test Stand is preparing to conduct tests on the powerpack component of the J-2X rocket engine, beginning in early 2012.

  20. Identification and analysis of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 in cynomolgus macaques.

    PubMed

    Uno, Yasuhiro; Hosaka, Shinya; Yamazaki, Hiroshi

    2014-12-01

    Cytochromes P450 (P450) are important for not only drug metabolism and toxicity, but also biosynthesis and metabolism of cholesterol and bile acids, and steroid synthesis. In cynomolgus macaques, widely used in biomedical research, we have characterized P450 cDNAs, which were isolated as expressed sequence tags of cynomolgus macaque liver. In this study, cynomolgus CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 cDNAs were characterized by sequence analysis, phylogenetic analysis and tissue expression pattern. By sequence analysis, these five cynomolgus P450s had high sequence identities (94-99%) to the human orthologs in amino acids. By phylogenetic analysis, each cynomolgus P450 was more closely related to the human ortholog as compared with the dog or rat ortholog. By quantitative polymerase chain reaction, among the 10 tissue types, CYP7A1 and CYP17A1 mRNAs were preferentially expressed in liver and adrenal gland, respectively. Cynomolgus CYP27A1 and CYP51A1 mRNAs were most abundantly expressed in liver and testis, respectively. Cynomolgus CYP20A1 mRNA was expressed in all the tissues, including brain and liver. Tissue expression patterns of each cynomolgus P450 were generally similar to that of the human ortholog. These results suggest the molecular similarities of CYP7A1, CYP17A1, CYP20A1, CYP27A1 and CYP51A1 between cynomolgus macaques and humans.

  1. Etiologic Agents and Diseases Found Associated with Clinical Aspergillosis in Falcons

    PubMed Central

    Tarello, Walter

    2011-01-01

    The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (n = 36) or multiple coinfections (n = 28). Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS) (n = 29), Caryospora sp. (n = 16), Serratospiculum seurati infestation (n = 14), cestodiasis (n = 6), bumblefoot (n = 5), trematodosis due to Strigea falconispalumbi (n = 5), trichomoniasis (n = 4), Babesia shortti (n = 4), Mannheimia (Pastorella) haemolytica (n = 4), interstitial hepatitis (n = 4), Escherichia coli (n = 3), and Clostridium perfringens enterotoxemia (n = 2). Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella) haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis. PMID:21754937

  2. Etiologic agents and diseases found associated with clinical aspergillosis in falcons.

    PubMed

    Tarello, Walter

    2011-01-01

    The aim of this study was to describe parasitological, microbiological, and pathological findings associated with the isolation of Aspergillus species in 94 clinically diseased captive falcons from Dubai. Concomitant agents and/or diseases were identified in 64 cases, causing either single (n = 36) or multiple coinfections (n = 28). Diagnoses found more often in association with aspergillosis were chronic fatigue and immune dysfunction syndrome (CFIDS) (n = 29), Caryospora sp. (n = 16), Serratospiculum seurati infestation (n = 14), cestodiasis (n = 6), bumblefoot (n = 5), trematodosis due to Strigea falconispalumbi (n = 5), trichomoniasis (n = 4), Babesia shortti (n = 4), Mannheimia (Pastorella) haemolytica (n = 4), interstitial hepatitis (n = 4), Escherichia coli (n = 3), and Clostridium perfringens enterotoxemia (n = 2). Compared with a control group of 2000 diseased falcons without evidence of aspergillosis, the prevalence of Babesia shortti, CFIDS, Mannheimia (Pastorella) haemolytica, Escherichia coli, and falcon herpes virus infection was conspicuously higher in association with aspergillosis. These entities may be considered suitable candidates as predisposing factors for the mycosis.

  3. Hermes A-1 Test Rockets

    NASA Technical Reports Server (NTRS)

    1950-01-01

    The first Hermes A-1 test rocket was fired at White Sand Proving Ground (WSPG). Hermes was a modified V-2 German rocket, utilizing the German aerodynamic configuration; however, internally it was a completely new design. Although it did not result in an operational vehicle, the information that was gathered in the process contributed directly to the development of the Redstone rocket.

  4. Pharmacokinetic-pharmacodynamic integration and modelling of oxytetracycline administered alone and in combination with carprofen in calves.

    PubMed

    Brentnall, C; Cheng, Z; McKellar, Q A; Lees, P

    2013-06-01

    The pharmacokinetic (PK) and pharmacodynamic (PD) profiles of oxytetracycline were investigated, when administered both alone and in the presence of carprofen, in healthy calves. The study comprised a four treatment, four sequences, and four period cross-over design and used a tissue cage model, which permitted the collection of serum, inflamed tissue cage fluid (exudate) and non-inflamed tissue cage fluid (transudate). There were no clinically relevant differences in the PK profile of oxytetracycline when administered alone and when administered with carprofen. PK-PD integration was undertaken for a pathogenic strain of Mannheimia haemolytic (A1 76/1), by correlating in vitro minimum inhibitory concentration (MIC) and time-kill data with in vivo PK data obtained in the cross-over study. Based on in vitro susceptibility in cation adjusted Mueller Hinton Broth (CAMHB) and in vivo determined PK variables, ratios of maximum concentration (Cmax) and area under curve (AUC) to MIC and time for which concentration exceeded MIC (T>MIC) were determined. The CAMHB MIC data satisfied integrated PK/PD relationships predicted to achieve efficacy for approximately 48 h after dosing; mean values for serum were 5.13 (Cmax/MIC), 49.3 h (T>MIC) and 126.6 h (AUC(96h)/MIC). Similar findings were obtained when oxytetracycline was administered in the presence of carprofen, with PK-PD indices based on MIC determined in CAMHB. However, PK-PD integration of data, based on oxytetracycline MICs determined in the biological fluids, serum, exudate and transudate, suggest that it possesses, at most, limited direct killing activity against the M. haemolytica strain A1 76/1; mean values for serum were 0.277 (Cmax/MIC), 0 h (T>MIC) and 6.84 h (AUC(96h)/MIC). The data suggest that the beneficial therapeutic effects of oxytetracycline may depend, at least in part, on actions other than direct inhibition of bacterial growth.

  5. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... consistent with respiratory system infection following challenge, including but not limited to lacrimation... vaccinates and controls shall each be challenged by the respiratory route with a (virulent) pneumonia... lesion scores cannot be demonstrated between vaccinates and controls using a scoring system approved...

  6. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... consistent with respiratory system infection following challenge, including but not limited to lacrimation... vaccinates and controls shall each be challenged by the respiratory route with a (virulent) pneumonia... lesion scores cannot be demonstrated between vaccinates and controls using a scoring system approved...

  7. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... consistent with respiratory system infection following challenge, including but not limited to lacrimation... vaccinates and controls shall each be challenged by the respiratory route with a (virulent) pneumonia... lesion scores cannot be demonstrated between vaccinates and controls using a scoring system approved...

  8. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... consistent with respiratory system infection following challenge, including but not limited to lacrimation... vaccinates and controls shall each be challenged by the respiratory route with a (virulent) pneumonia... lesion scores cannot be demonstrated between vaccinates and controls using a scoring system approved...

  9. 9 CFR 113.68 - Pasteurella Haemolytica Vaccine, Bovine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... consistent with respiratory system infection following challenge, including but not limited to lacrimation... vaccinates and controls shall each be challenged by the respiratory route with a (virulent) pneumonia... lesion scores cannot be demonstrated between vaccinates and controls using a scoring system approved...

  10. A-1 Test Stand work

    NASA Image and Video Library

    2010-01-13

    Employees at NASA's John C. Stennis Space Center work to maneuver a structural steam beam into place on the A-1 Test Stand on Jan. 13. The beam was one of several needed to form the thrust takeout structure that will support a new thrust measurement system being installed on the stand for future rocket engine testing. Once lifted onto the stand, the beams had to be hoisted into place through the center of the test stand, with only two inches of clearance on each side. The new thrust measurement system represents a state-of-the-art upgrade from the equipment installed more than 40 years ago when the test stand was first constructed.

  11. Comparison of antemortem antimicrobial treatment regimens to antimicrobial susceptibility patterns of postmortem lung isolates from feedlot cattle with bronchopneumonia.

    PubMed

    Lamm, Catherine G; Love, Brenda C; Krehbiel, Clint R; Johnson, Nicholas J; Step, Douglas L

    2012-03-01

    A retrospective study was performed to compare the treatment regimens in feedlot cattle that died with bovine respiratory disease (BRD) to the antimicrobial susceptibility patterns of the microorganisms isolated from lungs. Forty-three cattle submitted by the Willard Sparks Beef Research Center (WSBRC) to the Oklahoma Animal Disease Diagnostic Laboratory for postmortem examination during 2007 had bronchopneumonia (acute = 16, subacute = 5, or chronic = 22). Lungs from cattle were cultured aerobically (40 cattle) and for Mycoplasma spp. (34 cattle). Susceptibility panels were performed. At least 1 BRD pathogen (Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Mycoplasma bovis, or Arcanobacterium pyogenes) was isolated from 39 cattle, and 77% (30/39) had multiple organisms recovered. Mycoplasmal infections were common (25/34) and a major component of mixed infections (24/25). The majority (60%) of the M. haemolytica, P. multocida, and H. somni isolates were resistant to tetracycline. Most of the H. somni isolates (67%) were susceptible to tilmicosin (Ti), enrofloxacin (En), ceftiofur (Ce), and florfenicol, despite extensive treatment with Ti, En, and Ce (75% of isolates were from cattle that received each antimicrobial once). Most of the M. haemolytica (65%) and P. multocida (79%) isolates were susceptible to En and Ce, despite antemortem treatment of cattle with these antimicrobials. Hence, the current study reports a discrepancy between the antemortem treatment of clinical BRD and the susceptibility patterns of the bacteria isolated from lungs postmortem. Based on these findings, factors other than antimicrobial resistance are playing a role in the death of feedlot cattle with BRD.

  12. Comparative nitric oxide production by LPS-stimulated monocyte-derived macrophages from Ovis canadensis and Ovis aries.

    PubMed

    Sacco, R E; Waters, W R; Rudolph, K M; Drew, M L

    2006-01-01

    Bighorn sheep are more susceptible to respiratory infection by Mannheimia haemolytica than are domestic sheep. In response to bacterial challenge, macrophages produce a number of molecules that play key roles in the inflammatory response, including highly reactive nitrogen intermediates such as nitric oxide (NO). Supernatants from monocyte-derived macrophages cultured with M. haemolytica LPS were assayed for nitric oxide activity via measurement of the NO metabolite, nitrite. In response to LPS stimulation, bighorn sheep macrophages secreted significantly higher levels of NO compared to levels for non-stimulated macrophages. In contrast, levels of NO produced by domestic sheep macrophages in response to M. haemolytica LPS did not differ from levels detected in non-stimulated cell cultures. Nitrite levels detected in supernatants of LPS-stimulated bighorn macrophage cultures treated with an inducible nitric oxide synthase (INOS) inhibitor, N(G)-monomethyl-L-arginine, were similar to that observed in non-stimulated cultures indicating a role for the iNOS pathway.

  13. A1C Test and Diabetes

    MedlinePlus

    ... Diagnosis The A1C Test & Diabetes The A1C Test & Diabetes What is the A1C test? The A1C test ... A1C test be used to diagnose type 2 diabetes and prediabetes? Yes. In 2009, an international expert ...

  14. Blood Test: Hemoglobin A1C

    MedlinePlus

    ... TV, Video Games, and the Internet Blood Test: Hemoglobin A1c KidsHealth > For Parents > Blood Test: Hemoglobin A1c Print A A A What's in this ... de sangre: hemoglobina A1c What It Is A hemoglobin A1c (HbA1c) test is used to monitor long- ...

  15. Blood Test: Hemoglobin A1C

    MedlinePlus

    ... Your 1- to 2-Year-Old Blood Test: Hemoglobin A1c KidsHealth > For Parents > Blood Test: Hemoglobin A1c A A A What's in this article? ... de sangre: hemoglobina A1c What It Is A hemoglobin A1c (HbA1c) test is used to monitor long- ...

  16. Antimicrobial susceptibility monitoring of respiratory tract pathogens isolated from diseased cattle and pigs across Europe: the VetPath study.

    PubMed

    de Jong, Anno; Thomas, Valérie; Simjee, Shabbir; Moyaert, Hilde; El Garch, Farid; Maher, Kirsty; Morrissey, Ian; Butty, Pascal; Klein, Ulrich; Marion, Hervé; Rigaut, Delphine; Vallé, Michel

    2014-08-06

    VetPath is an ongoing pan-European antibiotic susceptibility monitoring programme collecting pathogens from diseased antimicrobial non-treated cattle, pigs and poultry. In the current study, 1001 isolates from cattle and pig respiratory tract infections were tested for their antimicrobial susceptibilities. Non-replicate lung samples or nasopharyngeal/nasal swabs were collected from animals with acute clinical signs in 11 countries during 2002-2006. Pasteurella multocida and Mannheimia haemolytica from cattle and P. multocida, Actinobacillus pleuropneumoniae and Streptococcus suis from pigs were isolated by standard methods. S. suis was also isolated from meningitis cases. MICs of 16 antibiotics were assessed centrally by broth microdilution following CLSI recommendations. Results were interpreted using CLSI breakpoints where available. P. multocida (231) and M. haemolytica (138) isolates were all susceptible to amoxicillin/clavulanic acid, ceftiofur, enrofloxacin and trimethoprim/sulfamethoxazole. Resistance to florfenicol and spectinomycin was 0.4% and 3.5% in P. multocida, respectively, and absent in M. haemolytica isolates. Tetracycline resistance was 5.7% and 14.6% for P. multocida and M. haemolytica. In pigs, 230 P. multocida, 220 A. pleuropneumoniae and 182 S. suis isolates were recovered. Resistance to amoxicillin/clavulanic acid, ceftiofur, enrofloxacin, florfenicol, tiamulin and tilmicosin was absent or <1%. Trimethoprim/sulfamethoxazole resistance was 3-6% and tetracycline resistance varied from 14.7% in A. pleuropneumoniae to 81.8% in S. suis. In conclusion, low resistance to antibiotics with defined clinical breakpoints, except for tetracycline, was observed among the major respiratory tract pathogens recovered from cattle and pigs. Since for approximately half of the antibiotics in this panel no CLSI-defined breakpoints were available, setting of the missing veterinary breakpoints is important.

  17. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 18 Conservation of Power and Water Resources 1 2010-04-01 2010-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes the...

  18. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 18 Conservation of Power and Water Resources 1 2013-04-01 2013-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes the...

  19. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 18 Conservation of Power and Water Resources 1 2012-04-01 2012-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes the...

  20. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 18 Conservation of Power and Water Resources 1 2014-04-01 2014-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes the...

  1. 14 CFR 374a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 14 Aeronautics and Space 4 2010-01-01 2010-01-01 false Purpose. 374a.1 Section 374a.1 Aeronautics and Space OFFICE OF THE SECRETARY, DEPARTMENT OF TRANSPORTATION (AVIATION PROCEEDINGS) SPECIAL REGULATIONS EXTENSION OF CREDIT BY AIRLINES TO FEDERAL POLITICAL CANDIDATES § 374a.1 Purpose. Section 401 of...

  2. 22 CFR 3a.1 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 22 Foreign Relations 1 2012-04-01 2012-04-01 false Definitions. 3a.1 Section 3a.1 Foreign Relations DEPARTMENT OF STATE GENERAL ACCEPTANCE OF EMPLOYMENT FROM FOREIGN GOVERNMENTS BY MEMBERS OF THE UNIFORMED SERVICES § 3a.1 Definitions. For purposes of this part— (a) Applicant means any person who...

  3. 18 CFR 3a.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 18 Conservation of Power and Water Resources 1 2011-04-01 2011-04-01 false Purpose. 3a.1 Section 3a.1 Conservation of Power and Water Resources FEDERAL ENERGY REGULATORY COMMISSION, DEPARTMENT OF ENERGY GENERAL RULES NATIONAL SECURITY INFORMATION General § 3a.1 Purpose. This part 3a describes the...

  4. 46 CFR 147A.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 46 Shipping 5 2012-10-01 2012-10-01 false Purpose. 147A.1 Section 147A.1 Shipping COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) DANGEROUS CARGOES INTERIM REGULATIONS FOR SHIPBOARD FUMIGATION General § 147A.1 Purpose. The purpose of this part is to prescribe the requirements for...

  5. 12 CFR 269a.1 - Party.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 4 2014-01-01 2014-01-01 false Party. 269a.1 Section 269a.1 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) DEFINITIONS § 269a.1 Party. The term Party means any person, employee, group of employees, labor organization...

  6. 12 CFR 269a.1 - Party.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 4 2013-01-01 2013-01-01 false Party. 269a.1 Section 269a.1 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) DEFINITIONS § 269a.1 Party. The term Party means any person, employee, group of employees, labor organization...

  7. 12 CFR 269a.1 - Party.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 12 Banks and Banking 3 2011-01-01 2011-01-01 false Party. 269a.1 Section 269a.1 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM DEFINITIONS § 269a.1 Party. The term Party means any person, employee, group of employees, labor organization, or bank as...

  8. 12 CFR 269a.1 - Party.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 4 2012-01-01 2012-01-01 false Party. 269a.1 Section 269a.1 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM (CONTINUED) DEFINITIONS § 269a.1 Party. The term Party means any person, employee, group of employees, labor organization...

  9. 12 CFR 269a.1 - Party.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Party. 269a.1 Section 269a.1 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE SYSTEM DEFINITIONS § 269a.1 Party. The term Party means any person, employee, group of employees, labor organization, or bank as...

  10. Nonspecific suppressive effect of bovine herpesvirus type 1 on bovine leukocyte functions.

    PubMed Central

    Filion, L G; McGuire, R L; Babiuk, L A

    1983-01-01

    The effect of bovine herpesvirus type 1 on the specific and nonspecific immune response of calves was examined. Animals with or without prior aerosol exposure to Pasteurella haemolytica serotype A1 were aerosol challenged with 10(8) PFU of virus. Blood and serum samples were taken before and after virus challenge for determining cell-mediated, humoral, and neutrophil responses. A significant depression of the blastogenic responses to phytohemagglutinin, P. haemolytica, and Pasteurella multocida and of neutrophil chemotactic response was observed 4 to 7 days after challenge. However, the antibacterial activity of neutrophils was not significantly affected by virus exposure. Anti-bovine herpesvirus type 1 antibody responses were detected 11 days postchallenge. A significant elevation of the anti-P. haemolytica antibody response (day 0 versus day +11) was detected in animals previously exposed to P. haemolytica. PMID:6311742

  11. 32 CFR 169a.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Purpose. 169a.1 Section 169a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM... Department of Defense (DoD) to determine whether needed commercial activities (CAs) should be accomplished by...

  12. 32 CFR 169a.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Purpose. 169a.1 Section 169a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM... Department of Defense (DoD) to determine whether needed commercial activities (CAs) should be accomplished by...

  13. 32 CFR 168a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Purpose. 168a.1 Section 168a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING NATIONAL DEFENSE SCIENCE AND... National Defense Science and Engineering Graduate (NDSEG) Fellowships, as required by 10 U.S.C. 2191. (b...

  14. 32 CFR 169a.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Purpose. 169a.1 Section 169a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM... Department of Defense (DoD) to determine whether needed commercial activities (CAs) should be accomplished by...

  15. 32 CFR 168a.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 1 2011-07-01 2011-07-01 false Purpose. 168a.1 Section 168a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING NATIONAL DEFENSE SCIENCE AND... National Defense Science and Engineering Graduate (NDSEG) Fellowships, as required by 10 U.S.C. 2191. (b...

  16. 32 CFR 169a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 1 2010-07-01 2010-07-01 false Purpose. 169a.1 Section 169a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING COMMERCIAL ACTIVITIES PROGRAM... Department of Defense (DoD) to determine whether needed commercial activities (CAs) should be accomplished by...

  17. 32 CFR 237a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Purpose. 237a.1 Section 237a.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PUBLIC AFFAIRS...) advertising defense themes and products. ...

  18. 32 CFR 168a.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 1 2012-07-01 2012-07-01 false Purpose. 168a.1 Section 168a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING NATIONAL DEFENSE SCIENCE AND... National Defense Science and Engineering Graduate (NDSEG) Fellowships, as required by 10 U.S.C. 2191. (b...

  19. 32 CFR 242a.1 - Applicability.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 2 2012-07-01 2012-07-01 false Applicability. 242a.1 Section 242a.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PUBLIC MEETING PROCEDURES OF THE BOARD OF REGENTS, UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES...

  20. 32 CFR 168a.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 1 2013-07-01 2013-07-01 false Purpose. 168a.1 Section 168a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING NATIONAL DEFENSE SCIENCE AND... National Defense Science and Engineering Graduate (NDSEG) Fellowships, as required by 10 U.S.C. 2191. (b...

  1. 32 CFR 242a.1 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 2 2010-07-01 2010-07-01 false Applicability. 242a.1 Section 242a.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PUBLIC MEETING PROCEDURES OF THE BOARD OF REGENTS, UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES...

  2. 32 CFR 242a.1 - Applicability.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 2 2013-07-01 2013-07-01 false Applicability. 242a.1 Section 242a.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PUBLIC MEETING PROCEDURES OF THE BOARD OF REGENTS, UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES...

  3. 32 CFR 168a.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 1 2014-07-01 2014-07-01 false Purpose. 168a.1 Section 168a.1 National Defense Department of Defense OFFICE OF THE SECRETARY OF DEFENSE DEFENSE CONTRACTING NATIONAL DEFENSE SCIENCE AND... National Defense Science and Engineering Graduate (NDSEG) Fellowships, as required by 10 U.S.C. 2191. (b...

  4. 32 CFR 242a.1 - Applicability.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 2 2014-07-01 2014-07-01 false Applicability. 242a.1 Section 242a.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PUBLIC MEETING PROCEDURES OF THE BOARD OF REGENTS, UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES...

  5. 32 CFR 242a.1 - Applicability.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 2 2011-07-01 2011-07-01 false Applicability. 242a.1 Section 242a.1 National Defense Department of Defense (Continued) OFFICE OF THE SECRETARY OF DEFENSE (CONTINUED) MISCELLANEOUS PUBLIC MEETING PROCEDURES OF THE BOARD OF REGENTS, UNIFORMED SERVICES UNIVERSITY OF THE HEALTH SCIENCES...

  6. 42 CFR 2a.1 - Applicability.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...(a)) provides that “ he Secretary may authorize persons engaged in research on mental health... regulations in this part establish procedures under which any person engaged in research on mental health... 42 Public Health 1 2010-10-01 2010-10-01 false Applicability. 2a.1 Section 2a.1 Public...

  7. Mastitis in sheep--The last 10 years and the future of research.

    PubMed

    Gelasakis, A I; Mavrogianni, V S; Petridis, I G; Vasileiou, N G C; Fthenakis, G C

    2015-12-14

    Bacterial mastitis is a significant welfare and financial problem in sheep flocks. This paper reviews the recently published literature, including publications that highlight the significance and virulence factors of the causal agents, especially Staphylococcus aureus and Mannheimia haemolytica, the primary causes of the disease. Research has also contributed to the understanding of risk factors, including genetic susceptibility of animals to infections, supporting future strategies for sustainable disease control. Pathogenetic mechanisms, including the role of the local defenses in the teat, have also been described and can assist formulation of strategies that induce local immune responses in the teat of ewes. Further to well-established diagnostic techniques, i.e., bacteriological tests and somatic cell counting, advanced methodologies, e.g., proteomics technologies, will likely contribute to more rapid and accurate diagnostics, in turn enhancing mastitis control efforts.

  8. Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex.

    PubMed

    Gershwin, Laurel J; Van Eenennaam, Alison L; Anderson, Mark L; McEligot, Heather A; Shao, Matt X; Toaff-Rosenstein, Rachel; Taylor, Jeremy F; Neibergs, Holly L; Womack, James

    2015-01-01

    Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described.

  9. Single Pathogen Challenge with Agents of the Bovine Respiratory Disease Complex

    PubMed Central

    Gershwin, Laurel J.; Van Eenennaam, Alison L.; Anderson, Mark L.; McEligot, Heather A.; Toaff-Rosenstein, Rachel; Taylor, Jeremy F.; Neibergs, Holly L.; Womack, James

    2015-01-01

    Bovine respiratory disease complex (BRDC) is an important cause of mortality and morbidity in cattle; costing the dairy and beef industries millions of dollars annually, despite the use of vaccines and antibiotics. BRDC is caused by one or more of several viruses (bovine respiratory syncytial virus, bovine herpes type 1 also known as infectious bovine rhinotracheitis, and bovine viral diarrhea virus), which predispose animals to infection with one or more bacteria. These include: Pasteurella multocida, Mannheimia haemolytica, Mycoplasma bovis, and Histophilus somni. Some cattle appear to be more resistant to BRDC than others. We hypothesize that appropriate immune responses to these pathogens are subject to genetic control. To determine which genes are involved in the immune response to each of these pathogens it was first necessary to experimentally induce infection separately with each pathogen to document clinical and pathological responses in animals from which tissues were harvested for subsequent RNA sequencing. Herein these infections and animal responses are described. PMID:26571015

  10. Causes of Pneumonia Epizootics among Bighorn Sheep, Western United States, 2008–2010

    PubMed Central

    Highland, Margaret A.; Baker, Katherine; Cassirer, E. Frances; Anderson, Neil J.; Ramsey, Jennifer M.; Mansfield, Kristin; Bruning, Darren L.; Wolff, Peregrine; Smith, Joshua B.; Jenks, Jonathan A.

    2012-01-01

    Epizootic pneumonia of bighorn sheep is a devastating disease of uncertain etiology. To help clarify the etiology, we used culture and culture-independent methods to compare the prevalence of the bacterial respiratory pathogens Mannheimia haemolytica, Bibersteinia trehalosi, Pasteurella multocida, and Mycoplasma ovipneumoniae in lung tissue from 44 bighorn sheep from herds affected by 8 outbreaks in the western United States. M. ovipneumoniae, the only agent detected at significantly higher prevalence in animals from outbreaks (95%) than in animals from unaffected healthy populations (0%), was the most consistently detected agent and the only agent that exhibited single strain types within each outbreak. The other respiratory pathogens were frequently but inconsistently detected, as were several obligate anaerobic bacterial species, all of which might represent secondary or opportunistic infections that could contribute to disease severity. These data provide evidence that M. ovipneumoniae plays a primary role in the etiology of epizootic pneumonia of bighorn sheep. PMID:22377321

  11. Antigenic secreted proteins from Haemophilus paragallinarum. A 110-kDa putative RTX protein.

    PubMed

    Mena-Rojas, Erika; Vázquez Cruz, Candelario; Vaca Pacheco, Sergio; García González, Octavio; Pérez-Márquez, Víctor M; Pérez-Méndez, Alma; Ibarra-Caballero, Jorge; de la Garza, Mireya; Zenteno, Edgar; Negrete-Abascal, Erasmo

    2004-03-12

    Haemophilus paragallinarum is the causal agent of infectious coryza, an economically important disease for the poultry industry. This bacterium secreted proteins of 25-110 kDa during its growth in brain heart infusion, tryptic soy broth, or Luria-Bertani glucose phosphate media, all lacking serum. Some of these proteins were recognized by sera from chickens experimentally infected with H. paragallinarum. A 110-kDa protein was recognized by a serum pool from convalescent-phase pigs naturally infected with Actinobacillus pleuropneumoniae, and also by a rabbit polyclonal serum against Apx I as well as a rabbit serum against Mannheimia haemolytica leukotoxin, suggesting the presence of an RTX-like protein in H. paragallinarum. H. paragallinarum secreted proteins could be important immunogens in the control of infectious coryza.

  12. Causes of pneumonia epizootics among bighorn sheep, Western United States, 2008-2010.

    PubMed

    Besser, Thomas E; Highland, Margaret A; Baker, Katherine; Cassirer, E Frances; Anderson, Neil J; Ramsey, Jennifer M; Mansfield, Kristin; Bruning, Darren L; Wolff, Peregrine; Smith, Joshua B; Jenks, Jonathan A

    2012-03-01

    Epizootic pneumonia of bighorn sheep is a devastating disease of uncertain etiology. To help clarify the etiology, we used culture and culture-independent methods to compare the prevalence of the bacterial respiratory pathogens Mannheimia haemolytica, Bibersteinia trehalosi, Pasteurella multocida, and Mycoplasma ovipneumoniae in lung tissue from 44 bighorn sheep from herds affected by 8 outbreaks in the western United States. M. ovipneumoniae, the only agent detected at significantly higher prevalence in animals from outbreaks (95%) than in animals from unaffected healthy populations (0%), was the most consistently detected agent and the only agent that exhibited single strain types within each outbreak. The other respiratory pathogens were frequently but inconsistently detected, as were several obligate anaerobic bacterial species, all of which might represent secondary or opportunistic infections that could contribute to disease severity. These data provide evidence that M. ovipneumoniae plays a primary role in the etiology of epizootic pneumonia of bighorn sheep.

  13. 32 CFR 383a.1 - Purpose.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... DEFENSE COMMISSARY AGENCY (DeCA) § 383a.1 Purpose. Pursuant to the authority vested in the Secretary of Defense under title 10, United States Code, this part establishes the Defense Commissary Agency (DeCA)...

  14. 32 CFR 383a.1 - Purpose.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... DEFENSE COMMISSARY AGENCY (DeCA) § 383a.1 Purpose. Pursuant to the authority vested in the Secretary of Defense under title 10, United States Code, this part establishes the Defense Commissary Agency (DeCA)...

  15. 32 CFR 383a.1 - Purpose.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... DEFENSE COMMISSARY AGENCY (DeCA) § 383a.1 Purpose. Pursuant to the authority vested in the Secretary of Defense under title 10, United States Code, this part establishes the Defense Commissary Agency (DeCA)...

  16. 32 CFR 383a.1 - Purpose.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... DEFENSE COMMISSARY AGENCY (DeCA) § 383a.1 Purpose. Pursuant to the authority vested in the Secretary of Defense under title 10, United States Code, this part establishes the Defense Commissary Agency (DeCA)...

  17. 32 CFR 383a.1 - Purpose.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... DEFENSE COMMISSARY AGENCY (DeCA) § 383a.1 Purpose. Pursuant to the authority vested in the Secretary of Defense under title 10, United States Code, this part establishes the Defense Commissary Agency (DeCA)...

  18. TMS installation at A-1 Test Stand

    NASA Image and Video Library

    2010-03-03

    Stennis Space Center employees maneuver a new thrust measurement system in preparation for its installation on the A-1 Test Stand on March 3. The system was fabricated by Thrust Measurement Systems in Illinois and represents a state-of-the-art upgrade from the equipment used on the stand for more than 40 years. The A-1 Test Stand is being upgraded to provide testing for the next generation of rocket engines for America's space program.

  19. TMS installation at A-1 Test Stand

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Stennis Space Center employees maneuver a new thrust measurement system in preparation for its installation on the A-1 Test Stand on March 3. The system was fabricated by Thrust Measurement Systems in Illinois and represents a state-of-the-art upgrade from the equipment used on the stand for more than 40 years. The A-1 Test Stand is being upgraded to provide testing for the next generation of rocket engines for America's space program.

  20. Investigation of polymerase chain reaction assays to improve detection of bacterial involvement in bovine respiratory disease.

    PubMed

    Bell, Colin J; Blackburn, Paul; Elliott, Mark; Patterson, Tony I A P; Ellison, Sean; Lahuerta-Marin, Angela; Ball, Hywel J

    2014-09-01

    Bovine respiratory disease (BRD) causes severe economic losses to the cattle farming industry worldwide. The major bacterial organisms contributing to the BRD complex are Mannheimia haemolytica, Histophilus somni, Mycoplasma bovis, Pasteurella multocida, and Trueperella pyogenes. The postmortem detection of these organisms in pneumonic lung tissue is generally conducted using standard culture-based techniques where the presence of therapeutic antibiotics in the tissue can inhibit bacterial isolation. In the current study, conventional and real-time polymerase chain reaction (PCR) assays were used to assess the prevalence of these 5 organisms in grossly pneumonic lung samples from 150 animals submitted for postmortem examination, and the results were compared with those obtained using culture techniques. Mannheimia haemolytica was detected in 51 cases (34%) by PCR and in 33 cases (22%) by culture, H. somni was detected in 35 cases (23.3%) by PCR and in 6 cases (4%) by culture, Myc. bovis was detected in 53 cases (35.3%) by PCR and in 29 cases (19.3%) by culture, P. multocida was detected in 50 cases (33.3%) by PCR and in 31 cases (20.7%) by culture, and T. pyogenes was detected in 42 cases (28%) by PCR and in 31 cases (20.7%) by culture, with all differences being statistically significant. The PCR assays indicated positive results for 111 cases (74%) whereas 82 cases (54.6%) were culture positive. The PCR assays have demonstrated a significantly higher rate of detection of all 5 organisms in cases of pneumonia in cattle in Northern Ireland than was detected by current standard procedures. © 2014 The Author(s).

  1. Methamphetamine regulation of sulfotransferase 1A1 and 2A1 expression in rat brain sections.

    PubMed

    Zhou, Tianyan; Huang, Chaoqun; Chen, Yue; Xu, Jiaojiao; Shanbhag, Preeti Devaraya; Chen, Guangping

    2013-01-01

    Sulfotransferase catalyzed sulfation regulates the biological activities of various neurotransmitters/hormones and detoxifies xenobiotics. Rat sulfotransferase rSULT1A1 catalyzes the sulfation of neurotransmitters and xenobiotic phenolic compounds. rSULT2A1 catalyzes the sulfation of hydroxysteroids and xenobiotic alcoholic compounds. In this work, Western blot and real-time RT-PCR were used to investigate the effect of methamphetamine on rSULT1A1 and rSULT2A1 protein and mRNA expression in rat cerebellum, frontal cortex, hippocampus, and striatum. After 1-day treatment, significant induction of rSULT1A1 was observed only in the cerebellum; rSULT2A1 was induced significantly in the cerebellum, frontal cortex, and hippocampus. After 7 days of exposure, rSULT1A1 was induced in the cerebellum, frontal cortex, and hippocampus, while rSULT2A1 was induced significantly in all four regions. Western blot results agreed with the real-time RT-PCR results, suggesting that the induction occurred at the gene transcriptional level. Results indicate that rSULT1A1 and rSULT2A1 are expressed in rat frontal cortex, cerebellum, striatum, and hippocampus. rSULT1A1 and rSULT2A1are inducible by methamphetamine in rat brain sections in a time dependable manner. rSULT2A1 is more inducible than rSULT1A1 by methamphetamine in rat brain sections. Induction activity of methamphetamine is in the order of cerebellum>frontal cortex, hippocampus>striatum. These results suggest that the physiological functions of rSULT1A1 and rSULT2A1 in different brain regions can be affected by methamphetamine.

  2. Last SSME test on A-1

    NASA Image and Video Library

    2006-09-29

    The Stennis Space Center conducted the final space shuttle main engine test on its A-1 Test Stand Friday. The A-1 Test Stand was the site of the first test on a shuttle main engine in 1975. Stennis will continue testing shuttle main engines on its A-2 Test Stand through the end of the Space Shuttle Program in 2010. The A-1 stand begins a new chapter in its operational history in October. It will be temporarily decommissioned to convert it for testing the J-2X engine, which will power the upper stage of NASA's new crew launch vehicle, the Ares I. Although this ends the stand's work on the Space Shuttle Program, it will soon be used for the rocket that will carry America's next generation human spacecraft, Orion.

  3. 38 CFR 8a.1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... INSURANCE § 8a.1 Definitions. (a) The term housing unit means a family dwelling or unit, together with the... Insurance (VMLI) means the mortgage protection life insurance authorized for veterans under 38 U.S.C. 2106. (c) The term initial amount of insurance means the amount of insurance corresponding in amount to the...

  4. 22 CFR 3a.1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... UNIFORMED SERVICES § 3a.1 Definitions. For purposes of this part— (a) Applicant means any person who requests approval under this part to accept any civil employment (and compensation therefor) from a foreign... part to continue such employment. (b) Uniformed services means the Armed Forces, the...

  5. NERVA Reactor Based on NRX A1

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This artist's concept from 1963 shows a proposed NERVA (Nuclear Engine for Rocket Vehicle Application) incorporating the NRX-A1, the first NERVA-type cold flow reactor. The NERVA engine, based on Kiwi nuclear reactor technology, was intended to power a RIFT (Reactor-In-Flight-Test) nuclear stage, for which Marshall Space Flight Center had development responsibility.

  6. 38 CFR 8a.1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 8a.1 Pensions, Bonuses, and Veterans' Relief DEPARTMENT OF VETERANS AFFAIRS VETERANS MORTGAGE LIFE..., acquired by an eligible veteran to be used as his or her residence after selling or otherwise disposing of title to the housing unit for which his or her grant was made. (b) The term Veterans Mortgage Life...

  7. 8 CFR 213a.1 - Definitions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... BEHALF OF IMMIGRANTS § 213a.1 Definitions. As used in this part, the term: Domicile means the place where... intending immigrants. The “household income” may not, however, include the income of an intending immigrant, unless the intending immigrant is either the sponsor's spouse or has the same principal residence as...

  8. 8 CFR 213a.1 - Definitions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... BEHALF OF IMMIGRANTS § 213a.1 Definitions. As used in this part, the term: Domicile means the place where... intending immigrants. The “household income” may not, however, include the income of an intending immigrant, unless the intending immigrant is either the sponsor's spouse or has the same principal residence as...

  9. 8 CFR 213a.1 - Definitions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... BEHALF OF IMMIGRANTS § 213a.1 Definitions. As used in this part, the term: Domicile means the place where... Support Contract Between Sponsor and Household Member, on behalf of the sponsor and intending immigrants. The “household income” may not, however, include the income of an intending immigrant, unless...

  10. 8 CFR 213a.1 - Definitions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... BEHALF OF IMMIGRANTS § 213a.1 Definitions. As used in this part, the term: Domicile means the place where... Support Contract Between Sponsor and Household Member, on behalf of the sponsor and intending immigrants. The “household income” may not, however, include the income of an intending immigrant, unless...

  11. 8 CFR 213a.1 - Definitions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... BEHALF OF IMMIGRANTS § 213a.1 Definitions. As used in this part, the term: Domicile means the place where... intending immigrants. The “household income” may not, however, include the income of an intending immigrant, unless the intending immigrant is either the sponsor's spouse or has the same principal residence as...

  12. Studies of membrane topology of mitochondrial cholesterol hydroxylases CYPs 27A1 and 11A1

    PubMed Central

    Mast, Natalia; Liao, Wei-Li; Turko, Illarion V.

    2010-01-01

    Mitochondrial cytochrome P450 enzymes (CYP or P450, EC 1.14.13.15) play an important role in metabolism of cholesterol. CYP27A1 hydroxylates cholesterol at position 27 and, thus, initiates cholesterol removal from many extrahepatic tissues. CYP11A1 is a steroidogenic P450 that converts cholesterol to pregnenolone, the first step in the biosynthesis of all steroid hormones. We utilized a new approach to study membrane topology of CYPs 27A1 and 11A1. This approach involves heterologous expression of membrane-bound P450 in E. coli, isolation of the P450-containing E. coli membranes, treatment of the membranes with protease, removal of the digested soluble portion and extraction of the membrane-associated peptides, which are then identified by mass spectrometry. By using this approach, we found four membrane-interacting peptides in CYP27A1, and two peptides in CYP11A1. Peptides in CYP27A1 represent a contiguous portion of the polypeptide chain (residues 210-251) corresponding to the putative F-G loop and adjacent portions of the F and G helices. Peptides in CYP11A1 are from the putative F-G loop (residues 218-225) and the C-terminal portion of the G helix (residues 238-250). This data is consistent with those obtained previously by us and others and provide new information about membrane topology of CYPs 27A1 and 11A1. PMID:18791760

  13. TMS installation at A-1 Test Stand

    NASA Technical Reports Server (NTRS)

    2010-01-01

    Employees at NASA's John C. Stennis Space Center complete installation of the new thrust measurement system on the A-1 Test Stand. The new TMS is a state-of-the-art upgrade from the previous system, which was installed when the testing structure was built in the 1960s. It is an advanced calibration system capable of measuring vertical and horizontal thrust loads with accuracy within 0.15 percent at 225,000 pounds. It also will allow engineers to measure thrust as they gimbal (or tilt) engines during tests. The new TMS is part of upgrades for the A-1 Test Stand in preparation for testing the next generation of American space program rocket engines.

  14. TMS installation at A-1 Test Stand

    NASA Image and Video Library

    2010-03-03

    A new thrust measurement system is lifted onto the A-1 Test Stand deck at NASA's John C. Stennis Space Center in preparation for its installation. The new system is a state-of-the-art upgrade for the testing structure, which is being prepared for testing of next-generation rocket engines. The system was fabricated by Thrust Measurement Systems in Illinois at a cost of about $3.5 million.

  15. TMS installation at A-1 Test Stand

    NASA Technical Reports Server (NTRS)

    2010-01-01

    A new thrust measurement system is lifted onto the A-1 Test Stand deck at NASA's John C. Stennis Space Center in preparation for its installation. The new system is a state-of-the-art upgrade for the testing structure, which is being prepared for testing of next-generation rocket engines. The system was fabricated by Thrust Measurement Systems in Illinois at a cost of about $3.5 million.

  16. Pathogens, patterns of pneumonia, and epidemiologic risk factors associated with respiratory disease in recently weaned cattle in Ireland.

    PubMed

    Murray, Gerard M; More, Simon J; Sammin, Dónal; Casey, Mìcheàl J; McElroy, Máire C; O'Neill, Rónan G; Byrne, William J; Earley, Bernadette; Clegg, Tracy A; Ball, Hywel; Bell, Colin J; Cassidy, Joseph P

    2017-01-01

    We examined the pathogens, morphologic patterns, and risk factors associated with bovine respiratory disease (BRD) in 136 recently weaned cattle ("weanlings"), 6-12 mo of age, that were submitted for postmortem examination to regional veterinary laboratories in Ireland. A standardized sampling protocol included routine microbiologic investigations as well as polymerase chain reaction and immunohistochemistry. Lungs with histologic lesions were categorized into 1 of 5 morphologic patterns of pneumonia. Fibrinosuppurative bronchopneumonia (49%) and interstitial pneumonia (48%) were the morphologic patterns recorded most frequently. The various morphologic patterns of pulmonary lesions suggest the involvement of variable combinations of initiating and compounding infectious agents that hindered any simple classification of the etiopathogenesis of the pneumonias. Dual infections were detected in 58% of lungs, with Mannheimia haemolytica and Histophilus somni most frequently recorded in concert. M. haemolytica (43%) was the most frequently detected respiratory pathogen; H. somni was also shown to be frequently implicated in pneumonia in this age group of cattle. Bovine parainfluenza virus 3 (BPIV-3) and Bovine respiratory syncytial virus (16% each) were the viral agents detected most frequently. Potential respiratory pathogens (particularly Pasteurella multocida, BPIV-3, and H. somni) were frequently detected (64%) in lungs that had neither gross nor histologic pulmonary lesions, raising questions regarding their role in the pathogenesis of BRD. The breadth of respiratory pathogens detected in bovine lungs by various detection methods highlights the diagnostic value of parallel analyses in respiratory disease postmortem investigation.

  17. Cloning and comparison of bighorn sheep CD18 with that of domestic sheep, goats, cattle, humans and mice.

    PubMed

    Liu, Weiguo; Brayton, Kelly A; Lagerquist, John; Foreyt, William J; Srikumaran, Subramaniam

    2006-03-15

    Previously, we have shown that CD18, the beta-subunit of beta(2)-integrins, serves as a receptor for leukotoxin (Lkt) secreted by Mannheimia (Pasteurella) haemolytica on bovine leukocytes. Anti-CD18 monoclonal antibodies (mAbs) inhibit Lkt-induced cytolysis of bighorn sheep (Ovis canadensis) leukocytes suggesting that CD18 may serve as a receptor for Lkt on the leukocytes of this species as well. Confirmation of bighorn sheep CD18 as a receptor for Lkt, and elucidation of the enhanced Lkt-susceptibility of bighorn sheep polymorphonuclear leukocytes (PMNs), necessitates the cloning and sequencing of cDNA encoding bighorn sheep CD18. Hence, in this study we cloned and sequenced the cDNA encoding CD18 of bighorn sheep, and compared with that of other animal species. The cDNA of bighorn sheep CD18 has an open reading frame (ORF) of 2310bp. CD18 sequences obtained individually from peripheral blood mononuclear cells (PBMCs) and PMNs were identical to each other. Comparison of the deduced 770-amino acid sequence of CD18 of bighorn sheep with that of domestic sheep, goats, cattle, humans and mice revealed 99, 98, 95, 82 and 80% identity, respectively. Availability of cloned bighorn sheep CD18 cDNA should allow the molecular characterization of M. haemolytica Lkt-receptor interactions in bighorn sheep and other ruminants that are susceptible to this disease.

  18. Domestic sheep (Ovis aries) Pasteurellaceae isolates from diagnostic submissions to the Caine Veterinary Teaching Center (1990-2004).

    PubMed

    Miller, David S; Weiser, Glen C; Ward, Alton C S; Drew, Mark L; Chapman, Phillip L

    2011-06-02

    A retrospective study of Pasteurellaceae isolated from domestic sheep (Ovis aries) was conducted. The aim was to identify Pasteurellaceae present in animals that were clinically healthy and others with evidence of respiratory disease. The bacteria had been isolated from samples submitted to the University of Idaho Caine Veterinary Teaching Center as part of disease diagnostic testing. The 844 isolates identified mainly three species of Pasteurellaceae: Mannheimia haemolytica, Pasteurella multocida, and Pasteurella (Bibersteinia) trehalosi. A total of 114 biovariants were identified among these three species. Individual biovariants were identified 1-180 times. Two of those (M. haemolytica 1 and P. (B.) trehalosi 2) constituted 36% of the isolates, and were the only biovariants sufficiently numerous to account for >7% of the total isolates. Samples were primarily submitted from sheep with signs of respiratory disease. Eighty percent of biovariants were identified most often in animals with signs of respiratory disease, but 26% of biovariants were isolated from both sheep with respiratory disease and apparently healthy sheep. P. multocida constituted 4.7% of isolates, and were exclusively associated with animals with respiratory disease. The ability of isolates to produce beta-hemolysis on culture media was not associated with animals with respiratory disease (odds ratio 0.77, 95% CI 0.50-1.19). The inference of this study is limited due to the retrospective study design. However, it is the first study that provides an extensive baseline list of biovariants associated with respiratory disease in domestic sheep.

  19. Molecular versus conventional culture for detection of respiratory bacterial pathogens in poultry.

    PubMed

    Ammar, A M; Abd El-Aziz, N K; Abd El Wanis, S; Bakry, N R

    2016-02-29

    Acute respiratory tract infections are leading causes of morbidity in poultry farms allover the world. Six pathogens; Escherichia coli, Mycoplasma gallisepticum, Staphylococcus aureus, Pasteurella multocida, Mannheimia haemolytica and Pseudomonas aeruginosa were involved in respiratory infections in poultry. Herein, conventional identification procedures and polymerase chain reaction (PCR) were applied for detection of the most common respiratory bacterial pathogens in clinical specimens of poultry obtained from 53 Egyptian farms with various respiratory problems and the results were compared statistically. The analyzed data demonstrated a significantly higher rate of detection of the most recovered microorganisms (P<0.05) by PCR comparing to classical culture procedures. Further, multiplex PCR could detect E. coli, M. gallisepticum, S. aureus and Ps. aeruginosa in a single reaction, however, M. haemolytica was reported in a uinplex system. According to PCR results, the most commonly recorded bacterial pathogens in examined poultry farms were E. coli and Ps. aeruginosa (54.71% each), followed by M. haemolylica (35.85%) and M. gallisepticum (20.75%). In conclusion, PCR assay offered an effective alternative to traditional typing methods for the identification and simultaneous detection of the most clinically relevant respiratory pathogens in poultry.

  20. A bighorn sheep die-off in southern Colorado involving a Pasteurellaceae strain that may have originated from syntopic cattle.

    PubMed

    Wolfe, Lisa L; Diamond, Brandon; Spraker, Terry R; Sirochman, Michael A; Walsh, Daniel P; Machin, Chandra M; Bade, Donald J; Miller, Michael W

    2010-10-01

    We investigated a pasteurellosis epizootic in free-ranging bighorn sheep (Ovis canadensis) wherein a Pasteurellaceae strain carried by syntopic cattle (Bos taurus) under severe winter conditions appeared to contribute to pneumonia in affected bighorns. Twenty-one moribund or dead bighorn sheep were found on the "Fossil Ridge" herd's winter range, Colorado, USA, between 13 December 2007 and 29 February 2008. Eight carcasses examined showed gross or microscopic evidence of acute to subacute fibrinous bronchopneumonia. All eight carcasses yielded at least one β-hemolytic Mannheimia haemolytica biogroup 1(±(G)) strain, and seven also yielded a β-hemolytic Bibersteinia trehalosi biogroup 4 (CDS) strain; evidence of Pasteurella multocida, Mycoplasma ovipneumoniae, and parainfluenza 3 and bovine respiratory syncytial viruses was also detected. Isolates of β-hemolytic Manneimia haemolytica biogroup 1(G) from a bighorn carcass and a syntopic cow showed 99.5% similarity in genetic fingerprints; B. trehalosi biogroup 4(CDS) isolates were ≥94.9% similar to an isolate from a nearby bighorn herd. Field and laboratory observations suggested that pneumonia in affected bighorns may have been caused by a combination of pathogens including two pathogenic Pasteurellaceae strains--one likely of cattle origin and one likely of bighorn origin--with infections in some cases perhaps exacerbated by other respiratory pathogens and severe weather conditions. Our and others' findings suggest that intimate interactions between wild sheep and cattle should be discouraged as part of a comprehensive approach to health management and conservation of North American wild sheep species.

  1. Human aldehyde dehydrogenase 3A1 (ALDH3A1) exhibits chaperone-like function.

    PubMed

    Voulgaridou, Georgia-Persephoni; Tsochantaridis, Ilias; Mantso, Theodora; Franco, Rodrigo; Panayiotidis, Mihalis I; Pappa, Aglaia

    2017-08-01

    Aldehyde dehydrogenase 3A1 (ALDH3A1) is a metabolic enzyme that catalyzes the oxidation of various aldehydes. Certain types of epithelial tissues in mammals, especially those continually exposed to environmental stress (e.g., corneal epithelium), express ALDH3A1 at high levels and its abundance in such tissues is perceived to help to maintain cellular homeostasis under conditions of oxidative stress. Metabolic as well as non-metabolic roles for ALDH3A1 have been associated with its mediated resistance to cellular oxidative stress. In this study, we provide evidence that ALDH3A1 exhibits molecular chaperone-like activity further supporting its multifunctional role. Specifically, we expressed and purified the human ALDH3A1 in E. coli and used the recombinant protein to investigate its in vitro ability to protect SmaI and citrate synthase (from precipitation and/or deactivation) under thermal stress conditions. Our results indicate that recombinant ALDH3A1 exhibits significant chaperone function in vitro. Furthermore, over-expression of the fused histidine-tagged ALDH3A1 confers host E. coli cells with enhanced resistance to thermal shock, while ALDH3A1 over-expression in the human corneal cell line HCE-2 was sufficient for protecting them from the cytotoxic effects of both hydrogen peroxide and tert-butyl hydroperoxide. These results further support the chaperone-like function of human ALDH3A1. Taken together, ALDH3A1, in addition to its primary metabolic role in fundamental cellular detoxification processes, appears to play an essential role in protecting cellular proteins against aggregation under stress conditions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Reliability assessment of a 1 MV LTD.

    SciTech Connect

    Portillo, Salvador; Chavez, Raymond; Molina, Isidro; Kim, Alexandre A.; Johnson, David L.; Maenchen, John Eric; Leckbee, Joshua J.; Ziska, Derek Raymond

    2005-07-01

    A 1 MV linear transformer driver (LTD) is being tested with a large area e-beam diode load at Sandia National Laboratories (SNL). The experiments will be utilized to determine the repeatability of the output pulse and the reliability of the components. The 1 MV accelerator is being used to determine the feasibility of designing a 6 MV LTD for radiography experiments. The peak voltage, risetime, and pulse width as well as the cavity timing jitter are analyzed to determine the repeatability of the output pulse.

  3. Decommissioning Project of Bohunice A1 NPP

    SciTech Connect

    Stubna, M.; Pekar, A.; Moravek, J.; Spirko, M.

    2002-02-26

    The first (pilot) nuclear power plant A1 in the Slovak Republic, situated on Jaslovske Bohunice site (60 km from Bratislava) with the capacity of 143 MWel, was commissioned in 1972 and was running with interruptions till 1977. A KS 150 reactor (HWGCR) with natural uranium as fuel, D2O as moderator and gaseous CO2 as coolant was installed in the A1 plant. Outlet steam from primary reactor coolant system with the temperature of 410 C was led to 6 modules of steam generators and from there to turbine generators. Refueling was carried out on-line at plant full power. The first serious incident associated with refueling occurred in 1976 when a locking mechanism at a fuel assembly failed. The core was not damaged during that incident and following a reconstruction of the damaged technology channel, the plant continued in operation. However, serious problems were occurring with the integrity of steam generators (CO2 gas on primary side, water and steam on secondary side) when the plant had to be shut down frequently due to failures and subsequent repairs. The second serious accident occurred in 1977 when a fuel assembly was overheated with a subsequent release of D2O into gas cooling circuit due to a human failure in the course of replacement of a fuel assembly. Subsequent rapid increase in humidity of the primary system resulted in damages of fuel elements in the core and the primary system was contaminated by fission products. In-reactor structures had been damaged, too. Activity had penetrated also into certain parts of the secondary system via leaking steam generators. Radiation situation in the course of both events on the plant site and around it had been below the level of limits specified. Based on a technical and economical justification of the demanding character of equipment repairs for the restoration of plant operation, and also due to a decision made not to continue with further construction of gas cooled reactors in Czechoslovakia, a decision was made in

  4. In vitro activity and rodent efficacy of clinafloxacin for bovine and swine respiratory disease.

    PubMed

    Sweeney, Michael T; Quesnell, Rebecca; Tiwari, Raksha; Lemay, Mary; Watts, Jeffrey L

    2013-01-01

    Clinafloxacin is a broad-spectrum fluoroquinolone that was originally developed and subsequently abandoned in the late 1990s as a human health antibiotic for respiratory diseases. The purpose of this study was to investigate the activity of clinafloxacin as a possible treatment for respiratory disease in cattle and pigs. Minimum inhibitory concentration (MIC) values were determined using Clinical and Laboratory Standards Institute recommended procedures with recent strains from the Zoetis culture collection. Rodent efficacy was determined in CD-1 mice infected systemically or intranasally with bovine Mannheimia haemolytica or Pasteurella multocida, or swine Actinobacillus pleuropneumoniae, and administered clinafloxacin for determination of ED50 (efficacious dose-50%) values. The MIC90 values for clinafloxacin against bovine P. multocida, M. haemolytica, Histophilus somni, and M. bovis were 0.125, 0.5, 0.125, and 1 μg/ml, respectively, and the MIC90 values against swine P. multocida, A. pleuropneumoniae, S. suis, and M. hyopneumoniae were í0.03, í0.03, 0.125, and í0.008 μg/ml, respectively. Efficacy in mouse models showed average ED50 values of 0.019 mg/kg/dose in the bovine M. haemolytica systemic infection model, 0.55 mg/kg in the bovine P. multocida intranasal lung challenge model, 0.08 mg/kg/dose in the bovine P. multocida systemic infection model, and 0.7 mg/kg/dose in the swine A. pleuropneumoniae systemic infection model. Clinafloxacin shows good in vitro activity and efficacy in mouse models and may be a novel treatment alternative for the treatment of respiratory disease in cattle and pigs.

  5. In vitro activity and rodent efficacy of clinafloxacin for bovine and swine respiratory disease

    PubMed Central

    Sweeney, Michael T.; Quesnell, Rebecca; Tiwari, Raksha; LeMay, Mary; Watts, Jeffrey L.

    2013-01-01

    Clinafloxacin is a broad-spectrum fluoroquinolone that was originally developed and subsequently abandoned in the late 1990s as a human health antibiotic for respiratory diseases. The purpose of this study was to investigate the activity of clinafloxacin as a possible treatment for respiratory disease in cattle and pigs. Minimum inhibitory concentration (MIC) values were determined using Clinical and Laboratory Standards Institute recommended procedures with recent strains from the Zoetis culture collection. Rodent efficacy was determined in CD-1 mice infected systemically or intranasally with bovine Mannheimia haemolytica or Pasteurella multocida, or swine Actinobacillus pleuropneumoniae, and administered clinafloxacin for determination of ED50 (efficacious dose-50%) values. The MIC90 values for clinafloxacin against bovine P. multocida, M. haemolytica, Histophilus somni, and M. bovis were 0.125, 0.5, 0.125, and 1 μg/ml, respectively, and the MIC90 values against swine P. multocida, A. pleuropneumoniae, S. suis, and M. hyopneumoniae were í0.03, í0.03, 0.125, and í0.008 μg/ml, respectively. Efficacy in mouse models showed average ED50 values of 0.019 mg/kg/dose in the bovine M. haemolytica systemic infection model, 0.55 mg/kg in the bovine P. multocida intranasal lung challenge model, 0.08 mg/kg/dose in the bovine P. multocida systemic infection model, and 0.7 mg/kg/dose in the swine A. pleuropneumoniae systemic infection model. Clinafloxacin shows good in vitro activity and efficacy in mouse models and may be a novel treatment alternative for the treatment of respiratory disease in cattle and pigs. PMID:23785362

  6. Diversity of bacterial species in the nasal cavity of sheep in the highlands of Ethiopia and first report of Histophilus somni in the country.

    PubMed

    Tesfaye, Biruk; Sisay Tessema, Tesfaye; Tefera, Genene

    2013-06-01

    A study was conducted to isolate bacterial species/pathogens from the nasal cavity of apparently healthy and pneumonic sheep. Nasal swabs were collected aseptically, transported in tryptose soya broth and incubated for 24 h. Then, each swab was streaked onto chocolate and blood agar for culture. Bacterial species were identified following standard bacteriological procedures. Accordingly, a total of 1,556 bacteria were isolated from 960 nasal swabs collected from three different highland areas of Ethiopia, namely Debre Berhan, Asella, and Gimba. In Debre Berhan, 140 Mannheimia haemolytica, 81 Histophilus somni, 57 Staphylococcus species, and 52 Bibersteinia trehalosi were isolated. While from Gimba M. haemolytica, Staphylococcus, Streptococcus, and H. somni were isolated at rates of 25.2, 15.9, 11.4, and 5.9 %, respectively, of the total 647 bacterial species. In Asella from 352 bacterial species isolated, 93 (26.4 %) were M. haemolytica, 48 (13.6 %) were Staphylococcus species, 26 (7.4 %) were B. trehalosi, and 17 (4.8 %) H. somni were recognized. Further identification and characterization using BIOLOG identification system Enterococcus avium and Sphingomonas sanguinis were identified at 100 % probability, while, H. somni and Actinobacillus lignerisii were suggested by the system. The study showed that a variety of bacterial species colonize the nasal cavity of the Ethiopian highland sheep with variable proportion between healthy and pneumonic ones. To our knowledge, this is the first report on isolation of H. somni, an important pathogen in cattle, from the respiratory tract of a ruminant species in the country.

  7. Role of Bibersteinia trehalosi, respiratory syncytial virus, and parainfluenza-3 virus in bighorn sheep pneumonia.

    PubMed

    Dassanayake, Rohana P; Shanthalingam, Sudarvili; Subramaniam, Renuka; Herndon, Caroline N; Bavananthasivam, Jegarubee; Haldorson, Gary J; Foreyt, William J; Evermann, James F; Herrmann-Hoesing, Lynn M; Knowles, Donald P; Srikumaran, Subramaniam

    2013-02-22

    Pneumonic bighorn sheep (BHS) have been found to be culture- and/or sero-positive for Bibersteinia trehalosi, respiratory syncytial virus (RSV), and parainfluenza-3 virus (PI-3). The objective of this study was to determine whether these pathogens can cause fatal pneumonia in BHS. In the first study, two groups of four BHS each were intra-tracheally administered with leukotoxin-positive (Group I) or leukotoxin-negative (Group II) B. trehalosi. All four animals in Group I developed severe pneumonia, and two of them died within 3 days. The other two animals showed severe pneumonic lesions on euthanasia and necropsy. Animals in Group II neither died nor showed gross pneumonic lesions on necropsy, suggesting that leukotoxin-positive, but not leukotoxin-negative, B. trehalosi can cause fatal pneumonia in BHS. In the second study, two other groups of four BHS (Groups III and IV) were intra-nasally administered with a mixture of RSV and PI-3. Four days later, RSV/PI-3-inoculated Group IV and another group of four BHS (Group V, positive control) were intra-nasally administered with Mannheimia haemolytica, the pathogen that consistently causes fatal pneumonia in BHS. All four animals in group III developed pneumonia, but did not die during the study period. However all four animals in Group IV, and three animals in Group V developed severe pneumonia and died within two days of M. haemolytica inoculation. The fourth animal in Group V showed severe pneumonic lesions on euthanasia and necropsy. These findings suggest that RSV/PI-3 can cause non-fatal pneumonia, but are not necessary predisposing agents for M. haemolytica-caused pneumonia of BHS.

  8. In Vitro Activity of Coumermycin A1

    PubMed Central

    Fedorko, Joseph; Katz, Sol; Allnoch, Hedi

    1969-01-01

    The in vitro activity of coumermycin A1 was compared with that of novobiocin, ampicillin, and minocycline. Coumermycin was found to be the most active antibiotic of the four against Staphylococcus aureus. It was about 50 times more active than novobiocin or minocycline against the strains tested. Coumermycin also showed good activity against group A streptococci and pneumococci, moderate activity against Escherichia coli, indole-positive Proteus species, and Pseudomonas aeruginosa, and poor activity against Klebsiella-Enterobacter and enterococci. Against P. mirabilis, however, coumermycin activity was almost equal to that of ampicillin. The new antibiotic was further found to be greatly reduced in activity in the presence of plasma, but its minimal inhibitory concentration was not greatly affected by inoculum size. Coumermycin was found to be bacteriostatic in its action, and resistance to it developed slowly. Also, cross-resistance was present with novobiocin but absent with ampicillin or minocycline. PMID:4391844

  9. J-2X installation on A-1

    NASA Image and Video Library

    2007-09-20

    Core components of the J-2X engine being designed for NASA's Constellation Program recently were installed on the A-1 Test Stand at NASA's Stennis Space Center near Bay St. Louis, Miss. Tests of the components, known as Powerpack 1A, will be conducted from November 2007 through February 2008. The Powerpack 1A test article consists of a gas generator and engine turbopumps originally developed for the Apollo Program that put Americans on the moon in the late 1960s and early 1970s. Engineers are testing these heritage components to obtain data that will help them modify the turbomachinery to meet the higher performance requirements of the Ares I and Ares V launch vehicles. The upcoming tests will simulate inlet and outlet conditions that would be present on the turbomachinery during a full-up engine hot-fire test.

  10. Dispersed fluorescence spectroscopy of the CBr2A1B1-X1A1 transition.

    PubMed

    Hsu, Hui-Ju; Chang, Wei-Zhong; Chang, Bor-Chen

    2005-06-21

    Dispersed fluorescence spectra following the excitation of the CBr2A1B1-X1A1 2 and 2 bands at visible wavelengths were acquired in a discharge supersonic free jet expansion using an intensified charge-coupled device (ICCD) detector. The dispersed fluorescence spectra show signal-to-noise ratios of up to 60 and extend out to a maximum red shift frequency of 6000 cm(-1). Complete and detailed vibrational structure of the ground singlet state (X1A1) was observed. Vibrational parameters including fundamental frequencies, anharmonicities, and coupling constants were determined for the CBr2 X1A1 state. Additional vibrational structure starting at approximately 3650 cm(-1) was observed and this indicates the singlet-triplet energy gap to be >10 kcal mol(-1).

  11. PLC Software Program for Leak Detector Station A1 SALW-LD-ST-A1

    SciTech Connect

    KOCH, M.R.

    2001-01-25

    This document describes the software program for the programmable logic controller for the leak detector station ''SALW-LD-ST-A1''. The appendices contains a copy of the printout of the software program.

  12. Continuous transformation of a -1/2 wedge disclination line to a +1/2 one

    NASA Astrophysics Data System (ADS)

    Fukuda, Jun-Ichi

    2010-04-01

    It is known that, in the order-parameter space S2/Z2 (a typical example being a uniaxial nematic liquid crystal in three dimensions), a -1/2 wedge disclination line and a +1/2 one are topologically equivalent and can thus be transformed continuously into each other. Here we report the realization of this transformation in a simulation of a cholesteric blue phase under an electric field.

  13. A 1-D dusty plasma photonic crystal

    SciTech Connect

    Mitu, M. L.; Ticoş, C. M.; Toader, D.; Banu, N.; Scurtu, A.

    2013-09-21

    It is demonstrated numerically that a 1-D plasma crystal made of micron size cylindrical dust particles can, in principle, work as a photonic crystal for terahertz waves. The dust rods are parallel to each other and arranged in a linear string forming a periodic structure of dielectric-plasma regions. The dispersion equation is found by solving the waves equation with the boundary conditions at the dust-plasma interface and taking into account the dielectric permittivity of the dust material and plasma. The wavelength of the electromagnetic waves is in the range of a few hundred microns, close to the interparticle separation distance. The band gaps of the 1-D plasma crystal are numerically found for different types of dust materials, separation distances between the dust rods and rod diameters. The distance between levitated dust rods forming a string in rf plasma is shown experimentally to vary over a relatively wide range, from 650 μm to about 1350 μm, depending on the rf power fed into the discharge.

  14. Architecture for a 1-GHz Digital RADAR

    NASA Technical Reports Server (NTRS)

    Mallik, Udayan

    2011-01-01

    An architecture for a Direct RF-digitization Type Digital Mode RADAR was developed at GSFC in 2008. Two variations of a basic architecture were developed for use on RADAR imaging missions using aircraft and spacecraft. Both systems can operate with a pulse repetition rate up to 10 MHz with 8 received RF samples per pulse repetition interval, or at up to 19 kHz with 4K received RF samples per pulse repetition interval. The first design describes a computer architecture for a Continuous Mode RADAR transceiver with a real-time signal processing and display architecture. The architecture can operate at a high pulse repetition rate without interruption for an infinite amount of time. The second design describes a smaller and less costly burst mode RADAR that can transceive high pulse repetition rate RF signals without interruption for up to 37 seconds. The burst-mode RADAR was designed to operate on an off-line signal processing paradigm. The temporal distribution of RF samples acquired and reported to the RADAR processor remains uniform and free of distortion in both proposed architectures. The majority of the RADAR's electronics is implemented in digital CMOS (complementary metal oxide semiconductor), and analog circuits are restricted to signal amplification operations and analog to digital conversion. An implementation of the proposed systems will create a 1-GHz, Direct RF-digitization Type, L-Band Digital RADAR--the highest band achievable for Nyquist Rate, Direct RF-digitization Systems that do not implement an electronic IF downsample stage (after the receiver signal amplification stage), using commercially available off-the-shelf integrated circuits.

  15. HDL/ApoA-1 infusion and ApoA-1 gene therapy in atherosclerosis

    PubMed Central

    Chyu, Kuang-Yuh; Shah, Prediman K.

    2015-01-01

    The HDL hypothesis stating that simply raising HDL cholesterol (HDL-C) may produce cardiovascular benefits has been questioned recently based on several randomized clinical trials using CETP inhibitors or niacin to raise HDL-C levels. However, extensive pre-clinical data support the vascular protective effects of administration of exogenous ApoA-1 containing preβ-HDL like particles. Several small proof-of-concept clinical trials using such HDL/ApoA-1 infusion therapy have shown encouraging results but definitive proof of efficacy must await large scale clinical trials. In addition to HDL infusion therapy an alternative way to exploit beneficial cardiovascular effects of HDL/ApoA-1 is to use gene transfer. Preclinical studies have shown evidence of benefit using this approach; however clinical validation is yet lacking. This review summarizes our current knowledge of the aforementioned strategies. PMID:26388776

  16. Diagnosis and Management of Patients with a1-Antitrypsin (A1AT) Deficiency

    PubMed Central

    Nelson, David; Teckman, Jeffrey; Di Bisceglie, Adrian; Brenner, David A.

    2012-01-01

    α1-antitrypsin (A1AT) deficiency is an autosomal co-dominant disease that can cause chronic liver disease, cirrhosis, and hepatocellular carcinoma (HCC) in children and adults and increases risk for emphysema in adults. The development of symptomatic disease varies—some patients have life-threatening symptoms in childhood whereas others remain asymptomatic and healthy into old age. As a result of this variability, patients present across multiple disciplines, including pediatrics, adult medicine, hepatology, genetics, and pulmonology. This can give physicians the mistaken impression that the condition is less common than it actually is, and can lead to fragmented care that omits critical interventions commonly performed other specialists. We sought to present a rational approach for hepatologists to manage adult patients with A1AT deficiency. PMID:22200689

  17. Polymorphisms of UGT1A1*6, UGT1A1*27 & UGT1A1*28 in three major ethnic groups from Malaysia.

    PubMed

    Teh, L K; Hashim, H; Zakaria, Z A; Salleh, M Z

    2012-08-01

    Genetic polymorphisms of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) have been associated with a wide variation of responses among patients prescribed with irinotecan. Lack of this enzyme is known to be associated with a high incidence of severe toxicity. The objective of this study was to investigate the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28), which are associated with reduced enzyme activity and increased irinotecan toxicity, in the three main ethnic groups in Malaysia (Malays, Chinese and Indians). A total of 306 healthy unrelated volunteers were screened for UGT1A1*28, UGT1A1*6 and UGT1A1*27. Blood samples (5 ml) were obtained from each subject and DNA was extracted. PCR based methods were designed and validated for detection of UGT1A1*, UUGT1A1*27 and UUGT1A1*28. Direct DNA sequencing was performed to validate the results of randomly selected samples. Malays and Indian have two-fold higher frequency of homozygous of UGT1A1*28 (7TA/7TA) which was 8 and 8.8 per cent, respectively compared to the Chinese (4.9%). However, the distribution of UGT1A1*6 and UGT1A1*27 showed no significant differences among them. UGT1A1*27 which has not been detected in Caucasian and African American population, was found in the Malaysian Malays (3.33%) and Malaysian Chinese (2.0%). There was interethnic variability in the frequency of UGT1A1*28 in the Malaysian population. Our results suggest that genotyping of UUGT1A1*6, UGT1A1*28 and UGT1A1*27 need to be performed before patients are prescribed with irinotecan due to their high prevalence of allelic variant which could lead to adverse drug reaction.

  18. Polymorphisms of UGT1A1*6, UGT1A1*27 & UGT1A1*28 in three major ethnic groups from Malaysia

    PubMed Central

    Teh, L. K.; Hashim, H.; Zakaria, Z. A.; Salleh, M. Z.

    2012-01-01

    Background & objectives: Genetic polymorphisms of uridine diphosphate glucuronyltransferase 1A1 (UGT1A1) have been associated with a wide variation of responses among patients prescribed with irinotecan. Lack of this enzyme is known to be associated with a high incidence of severe toxicity. The objective of this study was to investigate the prevalence of three different variants of UGT1A1 (UGT1A1*6, UGT1A1*27 and UGT1A1*28), which are associated with reduced enzyme activity and increased irinotecan toxicity, in the three main ethnic groups in Malaysia (Malays, Chinese and Indians). Methods: A total of 306 healthy unrelated volunteers were screened for UGT1A1*28, UGT1A1*6 and UGT1A1*27. Blood samples (5 ml) were obtained from each subject and DNA was extracted. PCR based methods were designed and validated for detection of UGT1A1*6, UGT1A1*27 and UGT1A1*28. Direct DNA sequencing was performed to validate the results of randomly selected samples. Results: Malays and Indian have two-fold higher frequency of homozygous of UGT1A1*28 (7TA/7TA) which was 8 and 8.8 per cent, respectively compared to the Chinese (4.9%). However, the distribution of UGT1A1*6 and UGT1A1*27 showed no significant differences among them. UGT1A1*27 which has not been detected in Caucasian and African American population, was found in the Malaysian Malays (3.33%) and Malaysian Chinese (2.0%). Interpretation & conclusions: There was interethnic variability in the frequency of UGT1A1*28 in the Malaysian population. Our results suggest that genotyping of UGT1A1*6, UGT1A1*28 and UGT1A1*27 need to be performed before patients are prescribed with irinotecan due to their high prevalence of allelic variant which could lead to adverse drug reaction. PMID:22960892

  19. Diagnostics for a 1.2 kA, 1 MeV, electron induction injector

    NASA Astrophysics Data System (ADS)

    Houck, T. L.; Anderson, D. E.; Eylon, S.; Henestroza, E.; Lidia, S. M.; Vanecek, D. L.; Westenskow, G. A.; Yu, S. S.

    1998-12-01

    We are constructing a 1.2 kA, 1 MeV, electron induction injector as part of the RTA program, a collaborative effort between LLNL and LBNL to develop relativistic klystrons for Two-Beam Accelerator applications. The RTA injector will also be used in the development of a high-gradient, low-emittance, electron source and beam diagnostics for the second axis of the Dual Axis Radiographic Hydrodynamic Test (DARHT) Facility. The electron source will be a 3.5″-diameter, thermionic, flat-surface, m-type cathode with a maximum shroud field stress of approximately 165 kV/cm. Additional design parameters for the injector include a pulse length of over 150 ns flat top (1% energy variation), and a normalized edge emittance of less than 200 π-mm-mr. Precise measurement of the beam parameters is required so that performance of the RTA injector can be confidently scaled to the 4 kA, 3 MeV, and 2-microsecond pulse parameters of the DARHT injector. Planned diagnostics include an isolated cathode with resistive divider for direct measurement of current emission, resistive wall and magnetic probe current monitors for measuring beam current and centroid position, capacitive probes for measuring A-K gap voltage, an energy spectrometer, and a pepperpot emittance diagnostic. Details of the injector, beam line, and diagnostics are presented.

  20. Hemoglobin variants detected by hemoglobin A1c (HbA1c) analysis and the effects on HbA1c measurements.

    PubMed

    Nasir, Nadzimah Mohd; Thevarajah, M; Yean, Chew Yee

    2010-04-01

    Hemoglobin (Hb) A1c is a tool widely used to monitor long-term glycemic control in diabetic patients. The objective of our study is to compare the HbA1c values measured on high performance liquid chromatography (HPLC) and immunoassay in patients who were detected to have hemoglobin variant after HbA1c analysis. We compared the HbA1c values measured using the Arkray Adams A1c HA-8160 (HPLC method) and Roche Cobas Integra (immunoturbidimetric method) from diabetic patients who were diagnosed with hemoglobin variants. Forty-three diabetic patients were diagnosed with hemoglobin variants: 13 elevated Hb F, 12 Hb E trait, seven Hb S trait, seven Hb D trait, two Hb E / beta-Thalassemia, one Hb C trait, and one homozygous Hb S. Knowledge of hemoglobin variants affecting HbA1c measurements is essential, in order to avoid mismanagement of diabetic patients.

  1. Cyclin A1 is expressed in mouse ovary.

    PubMed

    Wei, Hongquan; Li, Yuanhong; Zhao, Chen; Jiang, Xuejun; Chen, Hongduo; Lang, Ming-Fei; Sun, Jing

    2014-01-01

    Cyclin A1 belongs to the type-A cyclins and participates in cell cycle regulation. Since its discovery, cyclin A1 has been shown mostly in testis. It plays important roles in spermatogenesis. However, there were also reports on ovary expression of cyclin A1. Therefore, we intended to revisit the expression of cyclin A1 in mouse ovary. Our study showed that cyclin A1 was expressed at the mRNA level and the protein level in mouse ovary. Tissue staining revealed that cyclin A1 was expressed in maturating oocytes. With the recent data on the functions of cyclins in somatic and stem cells, we also discussed the possibilities of further studies of cyclin A1 in mouse oocytes and perhaps in the oogonial stem cells. Our findings not only add to the supportive evidence of cyclin A1 expression in oocytes, but also may promote more interest in exploring cyclin A1 functions in ovary.

  2. 26 CFR 1.643(a)-1 - Deduction for distributions.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... computation of distributable net income. ... 1.643(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Estates, Trusts, and Beneficiaries § 1.643(a)-1 Deduction for...

  3. 26 CFR 1.643(a)-1 - Deduction for distributions.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... computation of distributable net income. ... 1.643(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Estates, Trusts, and Beneficiaries § 1.643(a)-1 Deduction for...

  4. No association between COL3A1, COL6A1 or COL12A1 gene variants and range of motion.

    PubMed

    O'connell, Kevin; Posthumus, Michael; Collins, Malcolm

    2013-01-01

    Approximately 64-70% of the variability in joint range of motion (ROM) is heritable. A common variant within a type V collagen (COL5A1) gene is associated with joint range of motion. Like type V collagen, types III, VI and XII collagen are also involved in fibril assembly and/or diameter regulation. Mutations within the genes that encode these proteins, COL3A1, COL6A1 and COL12A1, also cause connective tissue hypermobility disorders and phenotypes. The aim of this study was to determine if variants within these genes are associated with measures of joint range of motion. Three hundred and fifty apparently healthy and physically active Caucasian participants were recruited. Anthropometric measurements were taken. Sit-and-reach (SR), straight leg raise (SLR) and total shoulder rotation (ShTR) range of motion were measured. All participants were genotyped for COL3A1 rs1800255, COL6A1 rs35796750 and COL12A1 rs970547. COL3A1 rs1800255, COL6A1 rs35796750 and COL12A1 rs970547 were not significantly associated with sit-and-reach, straight leg raise or total shoulder rotation range of motion. Furthermore, no significant age-genotype interaction effects were identified between the variants and range of motion measurements. None of the variants investigated in this study were significantly associated with any of the measures of range of motion used. Further studies are required to identify additional intrinsic and extrinsic factors that may determine range of motion, including the genetic component.

  5. 29 CFR 2550.404a-1 - Investment duties.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 29 Labor 9 2012-07-01 2012-07-01 false Investment duties. 2550.404a-1 Section 2550.404a-1 Labor... FIDUCIARY RESPONSIBILITY § 2550.404a-1 Investment duties. (a) In general. Section 404(a)(1)(B) of the... use in the conduct of an enterprise of a like character and with like aims. (b) Investment duties. (1...

  6. 29 CFR 2550.404a-1 - Investment duties.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 29 Labor 9 2011-07-01 2011-07-01 false Investment duties. 2550.404a-1 Section 2550.404a-1 Labor... FIDUCIARY RESPONSIBILITY § 2550.404a-1 Investment duties. (a) In general. Section 404(a)(1)(B) of the... use in the conduct of an enterprise of a like character and with like aims. (b) Investment duties. (1...

  7. 29 CFR 2550.404a-1 - Investment duties.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 29 Labor 9 2014-07-01 2014-07-01 false Investment duties. 2550.404a-1 Section 2550.404a-1 Labor... FIDUCIARY RESPONSIBILITY § 2550.404a-1 Investment duties. (a) In general. Section 404(a)(1)(B) of the... use in the conduct of an enterprise of a like character and with like aims. (b) Investment duties. (1...

  8. 29 CFR 2550.404a-1 - Investment duties.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 29 Labor 9 2013-07-01 2013-07-01 false Investment duties. 2550.404a-1 Section 2550.404a-1 Labor... FIDUCIARY RESPONSIBILITY § 2550.404a-1 Investment duties. (a) In general. Section 404(a)(1)(B) of the... use in the conduct of an enterprise of a like character and with like aims. (b) Investment duties. (1...

  9. 5 CFR Appendix A-1 to Subpart I... - Windchill Chart

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... ADMINISTRATION (GENERAL) Pay for Duty Involving Physical Hardship or Hazard Pt. 550, Subpt. I, App. A-1 Appendix A-1 to Subpart I of Part 550—Windchill Chart EC01SE91.002 windchill chart in non-metric units... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Windchill Chart A Appendix A-1 to Subpart...

  10. 5 CFR Appendix A-1 to Subpart I... - Windchill Chart

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... ADMINISTRATION (GENERAL) Pay for Duty Involving Physical Hardship or Hazard Pt. 550, Subpt. I, App. A-1 Appendix A-1 to Subpart I of Part 550—Windchill Chart EC01SE91.002 windchill chart in non-metric units... 5 Administrative Personnel 1 2013-01-01 2013-01-01 false Windchill Chart A Appendix A-1 to Subpart...

  11. 5 CFR Appendix A-1 to Subpart I... - Windchill Chart

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... ADMINISTRATION (GENERAL) Pay for Duty Involving Physical Hardship or Hazard Pt. 550, Subpt. I, App. A-1 Appendix A-1 to Subpart I of Part 550—Windchill Chart EC01SE91.002 windchill chart in non-metric units... 5 Administrative Personnel 1 2014-01-01 2014-01-01 false Windchill Chart A Appendix A-1 to Subpart...

  12. 5 CFR Appendix A-1 to Subpart I... - Windchill Chart

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... ADMINISTRATION (GENERAL) Pay for Duty Involving Physical Hardship or Hazard Pt. 550, Subpt. I, App. A-1 Appendix A-1 to Subpart I of Part 550—Windchill Chart EC01SE91.002 windchill chart in non-metric units... 5 Administrative Personnel 1 2011-01-01 2011-01-01 false Windchill Chart A Appendix A-1 to Subpart...

  13. 5 CFR Appendix A-1 to Subpart I... - Windchill Chart

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... ADMINISTRATION (GENERAL) Pay for Duty Involving Physical Hardship or Hazard Pt. 550, Subpt. I, App. A-1 Appendix A-1 to Subpart I of Part 550—Windchill Chart EC01SE91.002 windchill chart in non-metric units... 5 Administrative Personnel 1 2012-01-01 2012-01-01 false Windchill Chart A Appendix A-1 to Subpart...

  14. 26 CFR 40.6011(a)-1 - Returns.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Returns. 40.6011(a)-1 Section 40.6011(a)-1... TAXES EXCISE TAX PROCEDURAL REGULATIONS § 40.6011(a)-1 Returns. (a) In general—(1) Return required. The return of any tax to which this part 40 applies must be made on Form 720, Quarterly Federal Excise Tax...

  15. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 5 2010-04-01 2010-04-01 false Designated Roth Accounts. 1.402A-1 Section 1... (CONTINUED) INCOME TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.402A-1 Designated Roth Accounts. Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate account under...

  16. 26 CFR 48.4222(a)-1 - Registration.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 16 2013-04-01 2013-04-01 false Registration. 48.4222(a)-1 Section 48.4222(a)-1... TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Exemptions, Registration, Etc. § 48.4222(a)-1 Registration. (a) General rule. Except as provided in § 48.4222(b)-1, tax-free sales under section 4221 may...

  17. 26 CFR 48.4222(a)-1 - Registration.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Registration. 48.4222(a)-1 Section 48.4222(a)-1... TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Exemptions, Registration, Etc. § 48.4222(a)-1 Registration. (a) General rule. Except as provided in § 48.4222(b)-1, tax-free sales under section 4221 may...

  18. 26 CFR 48.4222(a)-1 - Registration.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 16 2012-04-01 2012-04-01 false Registration. 48.4222(a)-1 Section 48.4222(a)-1... TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Exemptions, Registration, Etc. § 48.4222(a)-1 Registration. (a) General rule. Except as provided in § 48.4222(b)-1, tax-free sales under section 4221 may...

  19. 26 CFR 48.4222(a)-1 - Registration.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Registration. 48.4222(a)-1 Section 48.4222(a)-1... TAXES MANUFACTURERS AND RETAILERS EXCISE TAXES Exemptions, Registration, Etc. § 48.4222(a)-1 Registration. (a) General rule. Except as provided in § 48.4222(b)-1, tax-free sales under section 4221 may...

  20. Aldehyde dehydrogenase 3A1 associates with prostate tumorigenesis

    PubMed Central

    Yan, J; De Melo, J; Cutz, J-C; Aziz, T; Tang, D

    2014-01-01

    Background: Accumulating evidence demonstrates high levels of aldehyde dehydrogense (ALDH) activity in human cancer types, in part, because of its association with cancer stem cells. Whereas ALDH1A1 and ALDH7A1 isoforms were reported to associate with prostate tumorigenesis, whether other ALDH isoforms are associated with prostate cancer (PC) remains unclear. Methods: ALDH3A1 expression was analysed in various PC cell lines. Xenograft tumours and 54 primary and metastatic PC tumours were stained using immunohistochemistry for ALDH3A1 expression. Results: In comparison with the non-stem counterparts, a robust upregulation of ALDH3A1 was observed in DU145-derived PC stem cells (PCSCs). As DU145 PCSCs produced xenograft tumours with more advanced features compared with those derived from DU145 cells, higher levels of ALDH3A1 were detected in the former; a dramatic elevation of ALDH3A1 occurred in DU145 cell-derived lung metastasis compared with local xenograft tumours. Furthermore, while ALDH3A1 was not observed in prostate glands, ALDH3A1 was clearly present in PIN, and further increased in carcinomas. In comparison with the paired local carcinomas, ALDH3A1 was upregulated in lymph node metastatic tumours; the presence of ALDH3A1 in bone metastatic PC was also demonstrated. Conclusions: We report here the association of ALDH3A1 with PC progression. PMID:24762960

  1. 26 CFR 1.1311(a)-1 - Introduction.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 11 2010-04-01 2010-04-01 true Introduction. 1.1311(a)-1 Section 1.1311(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Readjustment of Tax Between Years and Special Limitations § 1.1311(a)-1 Introduction....

  2. 26 CFR 1.501(a)-1 - Exemption from taxation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 7 2011-04-01 2009-04-01 true Exemption from taxation. 1.501(a)-1 Section 1.501(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(a)-1 Exemption from taxation. (a) In...

  3. 26 CFR 1.501(a)-1 - Exemption from taxation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 7 2010-04-01 2010-04-01 true Exemption from taxation. 1.501(a)-1 Section 1.501(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Exempt Organizations § 1.501(a)-1 Exemption from taxation. (a) In...

  4. Chiral dynamics of a1(1260) → 3π

    NASA Astrophysics Data System (ADS)

    Tegen, R.; Greiner, W.

    2003-06-01

    We calculate the sequential decays a1 rightarrow pisigma rightarrow 3pi and a1 rightarrow pirho rightarrow 3pi using chiral SU(2) otimes SU(2) current commutation relations. Proper vertices a1pisigma, sigmapipi, a1pirho, rhopipi are derived from Ward identities and yield energy-dependent decay widths Gammarhorightarrowpipi and Gammasigmarightarrowpipi necessary for the total Gammaa1rightarrow3pi decay width. Both sequential decays (via pisigma and pirho) are necessary to reproduce Gammatota1. We find evidence for a substantial quenching of the sigma rightarrow pipi decay width in a1 rightarrow pisigma rightarrow 3pi.

  5. Methods for Tumor Targeting with Salmonella typhimurium A1-R.

    PubMed

    Hoffman, Robert M; Zhao, Ming

    2016-01-01

    Salmonella typhimurium A1-R (S. typhimurium A1-R) has shown great preclinical promise as a broad-based anti-cancer therapeutic (please see Chapter 1 ). The present chapter describes materials and methods for the preclinical study of S. typhimurium A1-R in clinically-relevant mouse models. Establishment of orthotopic metastatic mouse models of the major cancer types is described, as well as other useful models, for efficacy studies of S. typhimurium A1-R or other tumor-targeting bacteria, as well. Imaging methods are described to visualize GFP-labeled S. typhimurium A1-R, as well as GFP- and/or RFP-labeled cancer cells in vitro and in vivo, which S. typhimurium A1-R targets. The mouse models include metastasis to major organs that are life-threatening to cancer patients including the liver, lung, bone, and brain and how to target these metastases with S. typhimurium A1-R. Various routes of administration of S. typhimurium A1-R are described with the advantages and disadvantages of each. Basic experiments to determine toxic effects of S. typhimurium A1-R are also described. Also described are methodologies for combining S. typhimurium A1-R and chemotherapy. The testing of S. typhimurium A1-R on patient tumors in patient-derived orthotopic xenograft (PDOX) mouse models is also described. The major methodologies described in this chapter should be translatable for clinical studies.

  6. Association between uridin diphosphate glucuronosylotransferase 1A1 (UGT1A1) gene polymorphism and neonatal hyperbilirubinemia.

    PubMed

    Mazur-Kominek, Katarzyna; Romanowski, Tomasz; Bielawski, Krzysztof; Kiełbratowska, Bogumiła; Preis, Krzysztof; Domżalska-Popadiuk, Iwona; Słomińska-Frączek, Magdalena; Sznurkowska, Katarzyna; Renke, Joanna; Plata-Nazar, Katarzyna; Śledzińska, Karolina; Sikorska-Wiśniewska, Grażyna; Góra-Gębka, Magdalena; Liberek, Anna

    2017-01-01

    To assess the prevalence of UGT1A1*28 and UGT1A1*60 polymorphisms of UGT1A1 gene and their association with hyperbilirubinemia. The study was performed at a single centre - at the Department of Obstetrics of the Medical University of Gdansk in Poland. DNA was isolated from Guthrie cards of 171 infants. Only full term newborns (gestational age 38-42 weeks) were included in the study. Fluorescent molecular probes were used for UGT1A1 promoter variation analysis. The presence of UGT1A1*28 polymorphism was detected with a dual-probe system, and UGT1A1*60 with a SimpleProbe™. Homozygous UGT1A1*28 and UGT1A1*60 genotypes were detected in 14.6% and 20.5% of the newborns, respectively. Homozygous (G/G) genotypes of UGT1A1*60 polymorphism were found in all of the UGT1A1*28 (i.e. (TA)7/(TA)7) homozygotes. More than 80% (55/66) of the children with "wild" type UGT1A1*28 genotype (where no polymorphism was detected) (i.e. (TA)6/(TA)6) carried the "wild" (T/T) genotype of UGT1A1*60 as well. The UGT1A1*28 polymorphism was detected more often among neonates with elevated bilirubin. Hyperbilirubinemia was diagnosed more frequently in boys. Polymorphisms of the UGT1A1 gene frequently co-exist in neonates. The presence of UGT1A1*28 polymorphism and male gender seem to predispose to neonatal hyperbilirubinemia.

  7. An abundant dysfunctional apolipoprotein A1 in human atheroma

    PubMed Central

    Huang, Ying; DiDonato, Joseph A.; Levison, Bruce S.; Schmitt, Dave; Li, Lin; Wu, Yuping; Buffa, Jennifer; Kim, Timothy; Gerstenecker, Gary; Gu, Xiaodong; Kadiyala, Chandra; Wang, Zeneng; Culley, Miranda K.; Hazen, Jennie E.; DiDonato, Anthony J.; Fu, Xiaoming; Berisha, Stela; Peng, Daoquan; Nguyen, Truc; Liang, Shaohong; Chuang, Chia-Chi; Cho, Leslie; Plow, Edward F.; Fox, Paul L.; Gogonea, Valentin; Tang, W.H. Wilson; Parks, John S.; Fisher, Edward A.; Smith, Jonathan D.; Hazen, Stanley L.

    2014-01-01

    Recent studies indicate high density lipoproteins (HDL) and their major structural protein, apolipoprotein A1 (apoA1), recovered from human atheroma, are dysfunctional and extensively oxidized by myeloperoxidase (MPO), while in vitro oxidation of apoA1/HDL by MPO impairs its cholesterol acceptor function. We developed a high affinity monoclonal antibody (mAb) that specifically recognizes apoA1/HDL modified by the MPO/H2O2/Cl-system using phage display affinity maturation. An oxindolyl alanine (2-OH-Trp) moiety at tryptophan 72 of apoA1 is the immunogenic epitope. Mutagenesis studies confirm a critical role for apoA1 Trp72 in MPO-mediated inhibition of ABCA1-dependent cholesterol acceptor activity of apoA1 in vitro and in vivo. ApoA1 containing a 2-OH-Trp72 group (oxTrp72-apoA1) is in low abundance within the circulation, but accounts for 20% of the apoA1 in atherosclerotic plaque. OxTrp72-apoA1 recovered from human atheroma or plasma was lipid-poor, virtually devoid of cholesterol acceptor activity, and demonstrated both potent pro-inflammatory activities on endothelial cells and impaired HDL biogenesis activity in vivo. Elevated oxTrp72-apoA1 levels in subjects presenting to a cardiology clinic (n=627) were associated with increased cardiovascular disease risk. Circulating oxTrp72-apoA1 levels may serve as a way to monitor a pro-atherogenic process in the artery wall. PMID:24464187

  8. SLC11A1 — EDRN Public Portal

    Cancer.gov

    SLC11A1 is a membrane associated divalent transition metal (iron and manganese) transporter involved in iron metabolism and host resistance to certain pathogens. SLC11A1 is a member of the solute carrier family 11 (proton-coupled divalent metal ion transporters) family. Mutations in the SLC11A1 gene are involved in susceptibility to infectious diseases such as tuberculosis and leprosy, and inflammatory diseases such as rheumatoid arthritis and Crohn disease. Several alternatively spliced variants have been identified.

  9. Hemoglobin A1c in predicting progression to diabetes.

    PubMed

    Nakagami, Tomoko; Tajima, Naoko; Oizumi, Toshihide; Karasawa, Shigeru; Wada, Kiriko; Kameda, Wataru; Susa, Shinji; Kato, Takeo; Daimon, Makoto

    2010-01-01

    The predictive value of hemoglobin A1c (HbA1c) in comparison to fasting plasma glucose (FPG) is evaluated for 5-year incident diabetes (DM), as HbA1c may be more practical than FPG in the screening for DM in the future. Of 1189 non-DM subjects aged 35-89 years old from the Funagata Study, 57 subjects (4.8%) had developed DM on the WHO criteria at 5-year follow-up. The odds ratio (95% confidence interval: CI) for a one standard deviation increase in FPG/HbA1c was 3.40 (2.44-4.74)/3.49 (2.42-5.02). The area under the receiver operating characteristic curve for FPG/HbA1c was 0.786 (95% CI: 0.719-0.853)/0.785 (0.714-0.855). The HbA1c corresponding to FPG 5.56 mmol/l was HbA1c 5.3%. There was no statistical difference in sensitivity between FPG 5.56 mmol/l and HbA1c 5.3% (61.4% vs. 56.1%), while specificity was higher in HbA1c 5.3% than FPG 5.56 mmol/l (87.8% vs. 82.5%, p-value<0.001). The fraction of incident case from those with baseline IGT was similar between the groups, however the fraction of people above the cut-off was significantly lower in HbA1c 5.3% than FPG 5.56 mmol/l (14.3% vs. 19.6%, p-value<0.001). HbA1c is similar to FPG to evaluate DM risk, and HbA1c could be practical and efficient to select subjects for intervention.

  10. Analysis of iceA1 transcription in Helicobacter pylori

    PubMed Central

    Donahue, John P.; Peek, Richard M.; van Doorn, Leen-Jan; Thompson, Stuart A.; Xu, Qing; Blaser, Martin J.; Miller, Geraldine G.

    2009-01-01

    Background Transcription of the Helicobacter pylori iceA1 gene is induced following adherence of the bacterium to gastric epithelial cells in vitro, suggesting that this gene might be involved in H. pylori pathogenesis. Consequently, the current studies were undertaken to characterize iceA1 transcription and to define the structure of iceA1-containing transcripts to evaluate the potential of this gene to encode functional proteins. Materials and Methods Northern blots and primer extension of RNA isolated from broth-grown cultures of various H. pylori strains was done to analyze iceA1-specific gene transcription. Reverse transcriptase (RT)-PCR was used to determine the levels of iceA1 transcripts derived from readthrough transcription that was initiated upstream of iceA1 within the 5′-flanking cysE gene. Results Three major transcripts were detected and each was initiated from a common promoter, designated PI. Two of these transcripts were comprised of iceA1 sequence, while a third transcript was dicistronic and included the downstream gene, hpyIM. In addition, 10-fold lower levels of iceA1 transcripts were initiated upstream of PI, either within or immediately downstream of cysE. Conclusions The present analysis suggests that iceA1 does not encode a functional protein in the majority of H. pylori strains. However, transcription of hpyIM, which encodes a highly conserved DNA adenine methyltransferase, is linked to iceA1 transcription. Therefore, iceA1 may affect H. pylori virulence in vivo through transcriptional regulation of hpyIM expression levels, which may result in specific variations in DNA methylation patterns leading to alteration in the expression of genes involved in virulence or pathogenesis. PMID:10672045

  11. Does A1c consistently reflect mean plasma glucose?

    PubMed

    Shrom, David; Sarwat, Samiha; Ilag, Liza; Bloomgarden, Zachary T

    2010-06-01

    A1c, a surrogate measure of glycemic control, is known to have a strong linear correlation with mean plasma glucose (MPG) when analyzed in populations of patients. However, clinically significant intersubject variability in this relationship exists, which suggests that A1c measurements may not reflect actual glycemic control in some patients. In the present study we explored the extent to which A1c accurately represents glycemic control, as measured by MPG, for individual patients. Data were pooled from randomized clinical trials in which A1c and self-monitored plasma glucose (SMPG) profiles were collected by patients with Type 2 diabetes treated with insulin analog regimens. MPG levels were calculated from SMPG profiles. Distributions of MPG were analyzed for patients within similar ranges of A1c (<6.5%, 6.5%-<7.5%, 7.5%-<8.5%, 8.5%-<9.5%, and ≥9.5%) and distributions of A1c were analyzed in patients within similar ranges of MPG (<6.1, 6.1-<7.8, 7.8-<9.4, 9.4-<11.1, and ≥11.1 mmol/L). Substantial proportions of patients had clinically significant differences between A1c and MPG. For example, among 260 patients with A1c between 6.5% and 7.5%, 10% had MPG levels <6.4 mmol/L, whereas 10% had MPG >9.5 mmol/L. Among the 224 patients with MPG levels ≥6.1 mmol/L and <7.8 mmol/L, 10% had A1c <6% and 10% had A1c >8.1%. In the absence of SMPG, A1c may inadequately represent glycemic control for many diabetic patients. © 2010 Ruijin Hospital, Shanghai Jiaotong University School of Medicine and Blackwell Publishing Asia Pty Ltd.

  12. 26 CFR 1.669(a)-1 - Limitation on tax.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 8 2014-04-01 2014-04-01 false Limitation on tax. 1.669(a)-1 Section 1.669(a)-1 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES (CONTINUED) Treatment of Excess Distributions of Trusts Applicable to Taxable...

  13. Annexin A1: Shifting the balance towards resolution and repair

    PubMed Central

    Leoni, Giovanna; Nusrat, Asma

    2017-01-01

    Epithelial barriers play an important role in regulating mucosal homeostasis. Upon injury, the epithelium and immune cells orchestrate repair mechanisms that re-establish homeostasis. This process is highly regulated by protein and lipid mediators such as Annexin A1. In this review, we focus on the pro-repair properties of Annexin A1. PMID:27232634

  14. SCGB2A1 — EDRN Public Portal

    Cancer.gov

    SCGB2A1, also known as MGB2 or mammaglobin B, encodes a small secreted protein from the secretoglobin family, part of the uterglobin superfamily. SCGB2A1 is normally expressed in the thymus, trachea, kidney, steroid responsive tissues (prostate, testis, uterus, breast and ovary) and salivary gland.

  15. 32 CFR 809a.1 - Random installation entry point checks.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Random installation entry point checks. 809a.1... Entry Policy § 809a.1 Random installation entry point checks. The installation commander determines when, where, and how to implement random checks of vehicles or pedestrians. The commander conducts random...

  16. 26 CFR 31.6402(a)-1 - Credits or refunds.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 15 2014-04-01 2014-04-01 false Credits or refunds. 31.6402(a)-1 Section 31... Revenue Code of 1954) § 31.6402(a)-1 Credits or refunds. (a) In general. For regulations under section 6402 of special application to credits or refunds of employment taxes, see §§ 31.6402(a)-2,...

  17. 26 CFR 31.6402(a)-1 - Credits or refunds.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 15 2013-04-01 2013-04-01 false Credits or refunds. 31.6402(a)-1 Section 31... Revenue Code of 1954) § 31.6402(a)-1 Credits or refunds. (a) In general. For regulations under section 6402 of special application to credits or refunds of employment taxes, see §§ 31.6402(a)-2,...

  18. Retinoid regulation of the zebrafish cyp26a1 promoter.

    PubMed

    Hu, Ping; Tian, Miao; Bao, Jie; Xing, Guangdong; Gu, Xingxing; Gao, Xiang; Linney, Elwood; Zhao, Qingshun

    2008-12-01

    Cyp26A1 is a major enzyme that controls retinoic acid (RA) homeostasis by metabolizing RA into bio-inactive metabolites. Previous research revealed that the mouse Cyp26A1 promoter has two canonical RA response elements (RAREs) that underlie the regulation of the gene by RA. Analyzing the 2,533-base pairs (2.5 k) genomic sequence upstream of zebrafish cyp26a1 start codon, we report that the two RAREs are conserved in zebrafish cyp26a1 promoter. Mutagenesis demonstrated that the two RAREs work synergistically in RA inducibility of cyp26a1. Fusing the 2.5 k (kilobase pairs) fragment to the enhanced yellow fluorescent protein (eYFP) reporter gene, we have generated two transgenic lines of zebrafish [Tg(cyp26a1:eYFP)]. The transgenic zebrafish display expression patterns similar to that of cyp26a1 gene in vivo. Consistent with the in vitro results, the reporter activity is RA inducible in embryos. Taken together, our results demonstrate that the 2.5 k fragment underlies the regulation of the zebrafish cyp26a1 gene by RA.

  19. Cysteine transporter SLC3A1 promotes breast cancer tumorigenesis

    PubMed Central

    Jiang, Yang; Cao, Yuan; Wang, Yongbin; Li, Wei; Liu, Xinyi; Lv, Yixuan; Li, Xiaoling; Mi, Jun

    2017-01-01

    Cysteine is an essential amino acid for infants, aged people as well as patients with metabolic disorders. Although the thiol group of cysteine side chain is active in oxidative reactions, the role of cysteine in cancer remains largely unknown. Here, we report that the expression level of the solute carrier family 3, member 1 (SLC3A1), the cysteine carrier, tightly correlated with clinical stages and patients' survival. Elevated SLC3A1 expression accelerated the cysteine uptake and the accumulation of reductive glutathione (GSH), leading to reduced reactive oxygen species (ROS). ROS increased the stability and activity of PP2Ac, resulting in decreased AKT activity. Hence, SLC3A1 activated the AKT signaling through inhibiting PP2A phosphatase activity. Consistently, overexpression of SLC3A1 enhanced tumorigenesis of breast cancer cells, whereas blocking SLC3A1 either with specific siRNA or SLC3A1 specific inhibitor sulfasalazine suppressed tumor growth and also abolished dietary NAC-promoted tumor growth. Collectively, our data demonstrate that SLC3A1 promotes cysteine uptake and determines cellular response to antioxidant N-acetylcysteine, suggesting SLC3A1 is a potential therapeutic target for breast cancer. PMID:28382174

  20. 26 CFR 1.926(a)-1 - Distributions to shareholders.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 10 2012-04-01 2012-04-01 false Distributions to shareholders. 1.926(a)-1... Distributions to shareholders. (a) Treatment of distributions. . For guidance, see § 1.926(a)-1T(a). (b) Order of distribution—(1) In general—(i) Distributions by a FSC received by a shareholder in a taxable...

  1. 26 CFR 1.926(a)-1 - Distributions to shareholders.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 10 2013-04-01 2013-04-01 false Distributions to shareholders. 1.926(a)-1... Distributions to shareholders. (a) Treatment of distributions. . For guidance, see § 1.926(a)-1T(a). (b) Order of distribution—(1) In general—(i) Distributions by a FSC received by a shareholder in a taxable...

  2. Note on the photoproduction of the charged A1

    NASA Astrophysics Data System (ADS)

    Condo, G. T.; Handler, T.

    1987-05-01

    Arguments made nearly 15 years ago by Fox and Hey are updated in the light of recent experimental findings. These indicate that the charge-exchange photoproduction of the A1 should dominate that of the A2. Consistency with the experimental data demands an A1 mass of 1335+/-20 MeV and width of 180+/-55 MeV.

  3. 42 CFR 5a.1 - Statutory basis and purpose.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 1 2013-10-01 2013-10-01 false Statutory basis and purpose. 5a.1 Section 5a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS RURAL... the Public Health Service Act. These provisions define “underserved rural community” for purposes of...

  4. 42 CFR 5a.1 - Statutory basis and purpose.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 1 2012-10-01 2012-10-01 false Statutory basis and purpose. 5a.1 Section 5a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS RURAL... the Public Health Service Act. These provisions define “underserved rural community” for purposes of...

  5. 42 CFR 5a.1 - Statutory basis and purpose.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 1 2014-10-01 2014-10-01 false Statutory basis and purpose. 5a.1 Section 5a.1 Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS RURAL... the Public Health Service Act. These provisions define “underserved rural community” for purposes of...

  6. 32 CFR 809a.1 - Random installation entry point checks.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Random installation entry point checks. 809a.1 Section 809a.1 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION INSTALLATION ENTRY POLICY, CIVIL DISTURBANCE INTERVENTION AND DISASTER ASSISTANCE...

  7. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 26 Internal Revenue 5 2013-04-01 2013-04-01 false Designated Roth Accounts. 1.402A-1 Section 1... Roth Accounts. Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate...(b) plan, to which designated Roth contributions are permitted to be made in lieu of...

  8. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 26 Internal Revenue 5 2012-04-01 2011-04-01 true Designated Roth Accounts. 1.402A-1 Section 1.402A... Roth Accounts. Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate...(b) plan, to which designated Roth contributions are permitted to be made in lieu of...

  9. 26 CFR 1.402A-1 - Designated Roth Accounts.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 26 Internal Revenue 5 2014-04-01 2014-04-01 false Designated Roth Accounts. 1.402A-1 Section 1... Roth Accounts. Q-1. What is a designated Roth account? A-1. A designated Roth account is a separate...(b) plan, to which designated Roth contributions are permitted to be made in lieu of...

  10. 26 CFR 1.665(a)-1 - Undistributed net income.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 8 2011-04-01 2011-04-01 false Undistributed net income. 1.665(a)-1 Section 1... Beginning Before January 1, 1969 § 1.665(a)-1 Undistributed net income. (a) The term undistributed net income means for any taxable year the distributable net income of the trust for that year as determined...

  11. 26 CFR 1.665(a)-1 - Undistributed net income.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Undistributed net income. 1.665(a)-1 Section 1... Before January 1, 1969 § 1.665(a)-1 Undistributed net income. (a) The term undistributed net income means for any taxable year the distributable net income of the trust for that year as determined under...

  12. 26 CFR 49.4262(a)-1 - Taxable transportation.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 16 2010-04-01 2010-04-01 true Taxable transportation. 49.4262(a)-1 Section 49...) MISCELLANEOUS EXCISE TAXES FACILITIES AND SERVICES EXCISE TAXES Transportation of Persons § 49.4262(a)-1 Taxable transportation. (a) In general. Unless excluded under section 4262(b) (see § 49.4262(b)-1), taxable...

  13. 26 CFR 49.4262(a)-1 - Taxable transportation.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 26 Internal Revenue 16 2011-04-01 2011-04-01 false Taxable transportation. 49.4262(a)-1 Section 49...) MISCELLANEOUS EXCISE TAXES FACILITIES AND SERVICES EXCISE TAXES Transportation of Persons § 49.4262(a)-1 Taxable transportation. (a) In general. Unless excluded under section 4262(b) (see § 49.4262(b)-1), taxable...

  14. Hemoglobin A1c and Self-Monitored Average Glucose

    PubMed Central

    Kovatchev, Boris P.; Breton, Marc D.

    2015-01-01

    Background: Previously we have introduced the eA1c—a new approach to real-time tracking of average glycemia and estimation of HbA1c from infrequent self-monitoring (SMBG) data, which was developed and tested in type 2 diabetes. We now test eA1c in type 1 diabetes and assess its relationship to the hemoglobin glycation index (HGI)—an established predictor of complications and treatment effect. Methods: Reanalysis of previously published 12-month data from 120 patients with type 1 diabetes, age 39.15 (14.35) years, 51/69 males/females, baseline HbA1c = 7.99% (1.48), duration of diabetes 20.28 (12.92) years, number SMBG/day = 4.69 (1.84). Surrogate fasting BG and 7-point daily profiles were derived from these unstructured SMBG data and the previously reported eA1c method was applied without any changes. Following the literature, we calculated HGI = HbA1c – (0.009 × Fasting BG + 6.8). Results: The correlation of eA1c with reference HbA1c was r = .75, and its deviation from reference was MARD = 7.98%; 95% of all eA1c values fell within ±20% from reference. The HGI was well approximated by a linear combination of the eA1c calibration factors: HGI = 0.007552*θ1 + 0.007645*θ2 – 3.154 (P < .0001); 73% of low versus moderate-high HGIs were correctly classified by the same factors as well. Conclusions: The eA1c procedure developed in type 2 diabetes to track in real-time changes in average glycemia and present the results in HbA1c-equivalent units has shown similar performance in type 1 diabetes. The eA1c calibration factors are highly predictive of the HGI, thereby explaining partially the biological variation causing discrepancies between HbA1c and its linear estimates from SMBG data. PMID:26553023

  15. Observation of B+-->a1+(1260)K0 and B0-->a1-(1260)K+.

    PubMed

    Aubert, B; Bona, M; Boutigny, D; Karyotakis, Y; Lees, J P; Poireau, V; Prudent, X; Tisserand, V; Zghiche, A; Garra Tico, J; Grauges, E; Lopez, L; Palano, A; Pappagallo, M; Eigen, G; Stugu, B; Sun, L; Abrams, G S; Battaglia, M; Brown, D N; Button-Shafer, J; Cahn, R N; Groysman, Y; Jacobsen, R G; Kadyk, J A; Kerth, L T; Kolomensky, Yu G; Kukartsev, G; Lopes Pegna, D; Lynch, G; Mir, L M; Orimoto, T J; Osipenkov, I L; Ronan, M T; Tackmann, K; Tanabe, T; Wenzel, W A; Del Amo Sanchez, P; Hawkes, C M; Watson, A T; Koch, H; Schroeder, T; Walker, D; Asgeirsson, D J; Cuhadar-Donszelmann, T; Fulsom, B G; Hearty, C; Mattison, T S; McKenna, J A; Barrett, M; Khan, A; Saleem, M; Teodorescu, L; Blinov, V E; Bukin, A D; Druzhinin, V P; Golubev, V B; Onuchin, A P; Serednyakov, S I; Skovpen, Yu I; Solodov, E P; Todyshev, K Yu; Bondioli, M; Curry, S; Eschrich, I; Kirkby, D; Lankford, A J; Lund, P; Mandelkern, M; Martin, E C; Stoker, D P; Abachi, S; Buchanan, C; Foulkes, S D; Gary, J W; Liu, F; Long, O; Shen, B C; Vitug, G M; Zhang, L; Paar, H P; Rahatlou, S; Sharma, V; Berryhill, J W; Campagnari, C; Cunha, A; Dahmes, B; Hong, T M; Kovalskyi, D; Richman, J D; Beck, T W; Eisner, A M; Flacco, C J; Heusch, C A; Kroseberg, J; Lockman, W S; Schalk, T; Schumm, B A; Seiden, A; Wilson, M G; Winstrom, L O; Chen, E; Cheng, C H; Fang, F; Hitlin, D G; Narsky, I; Piatenko, T; Porter, F C; Andreassen, R; Mancinelli, G; Meadows, B T; Mishra, K; Sokoloff, M D; Blanc, F; Bloom, P C; Chen, S; Ford, W T; Hirschauer, J F; Kreisel, A; Nagel, M; Nauenberg, U; Olivas, A; Smith, J G; Ulmer, K A; Wagner, S R; Zhang, J; Gabareen, A M; Soffer, A; Toki, W H; Wilson, R J; Winklmeier, F; Altenburg, D D; Feltresi, E; Hauke, A; Jasper, H; Merkel, J; Petzold, A; Spaan, B; Wacker, K; Klose, V; Kobel, M J; Lacker, H M; Mader, W F; Nogowski, R; Schubert, J; Schubert, K R; Schwierz, R; Sundermann, J E; Volk, A; Bernard, D; Bonneaud, G R; Latour, E; Lombardo, V; Thiebaux, Ch; Verderi, M; Clark, P J; Gradl, W; Muheim, F; Playfer, S; Robertson, A I; Watson, J E; Xie, Y; Andreotti, M; Bettoni, D; Bozzi, C; Calabrese, R; Cecchi, A; Cibinetto, G; Franchini, P; Luppi, E; Negrini, M; Petrella, A; Piemontese, L; Prencipe, E; Santoro, V; Anulli, F; Baldini-Ferroli, R; Calcaterra, A; de Sangro, R; Finocchiaro, G; Pacetti, S; Patteri, P; Peruzzi, I M; Piccolo, M; Rama, M; Zallo, A; Buzzo, A; Contri, R; Lo Vetere, M; Macri, M M; Monge, M R; Passaggio, S; Patrignani, C; Robutti, E; Santroni, A; Tosi, S; Chaisanguanthum, K S; Morii, M; Wu, J; Dubitzky, R S; Marks, J; Schenk, S; Uwer, U; Bard, D J; Dauncey, P D; Flack, R L; Nash, J A; Panduro Vazquez, W; Tibbetts, M; Behera, P K; Chai, X; Charles, M J; Mallik, U; Cochran, J; Crawley, H B; Dong, L; Eyges, V; Meyer, W T; Prell, S; Rosenberg, E I; Rubin, A E; Gao, Y Y; Gritsan, A V; Guo, Z J; Lae, C K; Denig, A G; Fritsch, M; Schott, G; Arnaud, N; Béquilleux, J; D'Orazio, A; Davier, M; Grosdidier, G; Höcker, A; Lepeltier, V; Le Diberder, F; Lutz, A M; Pruvot, S; Rodier, S; Roudeau, P; Schune, M H; Serrano, J; Sordini, V; Stocchi, A; Wang, W F; Wormser, G; Lange, D J; Wright, D M; Bingham, I; Burke, J P; Chavez, C A; Fry, J R; Gabathuler, E; Gamet, R; Hutchcroft, D E; Payne, D J; Schofield, K C; Touramanis, C; Bevan, A J; George, K A; Di Lodovico, F; Sacco, R; Cowan, G; Flaecher, H U; Hopkins, D A; Paramesvaran, S; Salvatore, F; Wren, A C; Brown, D N; Davis, C L; Allison, J; Bailey, D; Barlow, N R; Barlow, R J; Chia, Y M; Edgar, C L; Lafferty, G D; West, T J; Yi, J I; Anderson, J; Chen, C; Jawahery, A; Roberts, D A; Simi, G; Tuggle, J M; Blaylock, G; Dallapiccola, C; Hertzbach, S S; Li, X; Moore, T B; Salvati, E; Saremi, S; Cowan, R; Dujmic, D; Fisher, P H; Koeneke, K; Sciolla, G; Spitznagel, M; Taylor, F; Yamamoto, R K; Zhao, M; Zheng, Y; McLachlin, S E; Patel, P M; Robertson, S H; Lazzaro, A; Palombo, F; Bauer, J M; Cremaldi, L; Eschenburg, V; Godang, R; Kroeger, R; Sanders, D A; Summers, D J; Zhao, H W; Brunet, S; Côté, D; Simard, M; Taras, P; Viaud, F B; Nicholson, H; De Nardo, G; Fabozzi, F; Lista, L; Monorchio, D; Sciacca, C; Baak, M A; Raven, G; Snoek, H L; Jessop, C P; Knoepfel, K J; Losecco, J M; Benelli, G; Corwin, L A; Honscheid, K; Kagan, H; Kass, R; Morris, J P; Rahimi, A M; Regensburger, J J; Sekula, S J; Wong, Q K; Blount, N L; Brau, J; Frey, R; Igonkina, O; Kolb, J A; Lu, M; Rahmat, R; Sinev, N B; Strom, D; Strube, J; Torrence, E; Gagliardi, N; Gaz, A; Margoni, M; Morandin, M; Pompili, A; Posocco, M; Rotondo, M; Simonetto, F; Stroili, R; Voci, C; Ben-Haim, E; Briand, H; Calderini, G; Chauveau, J; David, P; Del Buono, L; de la Vaissière, Ch; Hamon, O; Leruste, Ph; Malclès, J; Ocariz, J; Perez, A; Prendki, J; Gladney, L; Biasini, M; Covarelli, R; Manoni, E; Angelini, C; Batignani, G; Bettarini, S; Carpinelli, M; Cenci, R; Cervelli, A; Forti, F; Giorgi, M A; Lusiani, A; Marchiori, G; Mazur, M A; Morganti, M; Neri, N; Paoloni, E; Rizzo, G; Walsh, J J; Biesiada, J; Elmer, P; Lau, Y P; Lu, C; Olsen, J; Smith, A J S; Telnov, A V; Baracchini, E; Bellini, F; Cavoto, G; Del Re, D; Di Marco, E; Faccini, R; Ferrarotto, F; Ferroni, F; Gaspero, M; Jackson, P D; Li Gioi, L; Mazzoni, M A; Morganti, S; Piredda, G; Polci, F; Renga, F; Voena, C; Ebert, M; Hartmann, T; Schröder, H; Waldi, R; Adye, T; Castelli, G; Franek, B; Olaiya, E O; Roethel, W; Wilson, F F; Emery, S; Escalier, M; Gaidot, A; Ganzhur, S F; Hamel de Monchenault, G; Kozanecki, W; Vasseur, G; Yèche, Ch; Zito, M; Chen, X R; Liu, H; Park, W; Purohit, M V; White, R M; Wilson, J R; Allen, M T; Aston, D; Bartoldus, R; Bechtle, P; Claus, R; Coleman, J P; Convery, M R; Dingfelder, J C; Dorfan, J; Dubois-Felsmann, G P; Dunwoodie, W; Field, R C; Glanzman, T; Gowdy, S J; Graham, M T; Grenier, P; Hast, C; Innes, W R; Kaminski, J; Kelsey, M H; Kim, H; Kim, P; Kocian, M L; Leith, D W G S; Li, S; Luitz, S; Luth, V; Lynch, H L; Macfarlane, D B; Marsiske, H; Messner, R; Muller, D R; O'Grady, C P; Ofte, I; Perazzo, A; Perl, M; Pulliam, T; Ratcliff, B N; Roodman, A; Salnikov, A A; Schindler, R H; Schwiening, J; Snyder, A; Su, D; Sullivan, M K; Suzuki, K; Swain, S K; Thompson, J M; Va'vra, J; Wagner, A P; Weaver, M; Wisniewski, W J; Wittgen, M; Wright, D H; Yarritu, A K; Yi, K; Young, C C; Ziegler, V; Burchat, P R; Edwards, A J; Majewski, S A; Miyashita, T S; Petersen, B A; Wilden, L; Ahmed, S; Alam, M S; Bula, R; Ernst, J A; Jain, V; Pan, B; Saeed, M A; Wappler, F R; Zain, S B; Krishnamurthy, M; Spanier, S M; Eckmann, R; Ritchie, J L; Ruland, A M; Schilling, C J; Schwitters, R F; Izen, J M; Lou, X C; Ye, S; Bianchi, F; Gallo, F; Gamba, D; Pelliccioni, M; Bomben, M; Bosisio, L; Cartaro, C; Cossutti, F; Della Ricca, G; Lanceri, L; Vitale, L; Azzolini, V; Lopez-March, N; Martinez-Vidal, F; Milanes, D A; Oyanguren, A; Albert, J; Banerjee, Sw; Bhuyan, B; Hamano, K; Kowalewski, R; Nugent, I M; Roney, J M; Sobie, R J; Harrison, P F; Ilic, J; Latham, T E; Mohanty, G B; Band, H R; Chen, X; Dasu, S; Flood, K T; Hollar, J J; Kutter, P E; Pan, Y; Pierini, M; Prepost, R; Wu, S L; Neal, H

    2008-02-08

    We present branching fraction measurements of the decays B(+)-->a(1)(+)(1260)K(0) and B(0)-->a(1)(-)(1260)K(+) with a(1)(+/-)(1260)-->pi(-/+)pi(+/-)pi(+/-). The data sample corresponds to 383 x 10(6) BB pairs produced in e(+)e(-) annihilation through the Upsilon(4S) resonance. We measure the products of the branching fractions B(B(+)-->a(1)(+)(1260)K(0)B(a(1)(+)(1260)-->pi(-)pi(+)pi(+))=(17.4+/-2.5+/-2.2) x 10(-6) and B(B(0)-->a(1)(-)(1260)K(+)B(a(1)(-)(1260)-->pi(+)pi(-)pi(-)) = (8.2+/-1.5+/-1.2) x 10(-6). We also measure the charge asymmetries A(ch)(B(+)-->a(1)(+)(1260)K(0) = 0.12+/-0.11+/-0.02 and A(ch)(B(0)-->a(1)(-)(1260)K+) = -0.16+/-0.12+/-0.01. The first uncertainty quoted is statistical and the second is systematic.

  16. The A1 and A1B proteins of heterogeneous nuclear ribonucleoparticles modulate 5' splice site selection in vivo.

    PubMed Central

    Yang, X; Bani, M R; Lu, S J; Rowan, S; Ben-David, Y; Chabot, B

    1994-01-01

    Recent in vitro results suggest that the heterogeneous nuclear ribonucleoparticle (hnRNP) A1 protein modulates alternative splicing by favoring distal 5' splice site (5'SS) selection and exon skipping. We used a mouse erythroleukemia (MEL) cell line (CB3C7) deficient in the expression of hnRNP A1 to test whether variations in hnRNP A1 and AlB protein levels affected alternative splicing in vivo. In contrast to A1-expressing MEL cell lines, CB3C7 cells preferentially selected the proximal 13S and 12S 5'SS on the adenovirus E1A pre-mRNA. Transiently expressing the A1 or A1B cDNA in CB3C7 cells shifted 5'SS selection toward the more distal 9S donor site. A1 protein synthesis was required for this effect since the expression of a mutated A1 cDNA did not affect 5'SS selection. These results demonstrate that in vivo variations in hnRNP A1 protein levels can influence 5'SS selection. Images PMID:8041722

  17. A1/Bfl-1 in leukocyte development and cell death

    PubMed Central

    Ottina, Eleonora; Tischner, Denise; Herold, Marco J.; Villunger, Andreas

    2012-01-01

    The function of the anti-apoptotic Bcl-2 family member Bcl2a1/Bfl-1/A1 is poorly understood due to the lack of appropriate loss-of-function mouse models and redundant effects with other Bcl-2 pro-survival proteins upon overexpression. Expression analysis of A1 suggests predominant roles in leukocyte development, their survival upon viral or bacterial infection, as well as during allergic reactions. In addition, A1 has been implicated in autoimmunity and the pathology and therapy resistance of hematological as well as solid tumors that may aberrantly express this protein. In this review, we aim to summarize current knowledge on A1 biology, focusing on its role in the immune system and compare it to that of other pro-survival Bcl-2 proteins. PMID:22342458

  18. Tumor-Targeting Salmonella typhimurium A1-R: An Overview.

    PubMed

    Hoffman, Robert M

    2016-01-01

    The present chapter reviews the development of the tumor-targeting amino-acid auxotrophic strain S. typhimurium A1 and the in vivo selection and characterization of the high-tumor-targeting strain S. typhimurium A1-R. Efficacy of S. typhimurium A1-R in nude-mouse models of prostate, breast, pancreatic, and ovarian cancer, as well as sarcoma and glioma in orthotopic mouse models is described. Also reviewed is efficacy of S. typhimurium A1-R targeting of primary bone tumor and lung metastasis of high-grade osteosarcoma, breast-cancer brain metastasis, and experimental breast-cancer bone metastasis in orthotopic mouse models. The efficacy of S. typhimurium A1-R on pancreatic cancer stem cells, on pancreatic cancer in combination with anti-angiogenic agents, as well as on cervical cancer, soft-tissue sarcoma, and pancreatic cancer patient-derived orthotopic xenograft (PDOX) mouse models, is also described.

  19. Natural products isolated from Mexican medicinal plants: novel inhibitors of sulfotransferases, SULT1A1 and SULT2A1.

    PubMed

    Mesía-Vela, S; Sańchez, R I; Estrada-Muñiz, E; Alavez-Solano, D; Torres-Sosa, C; Jiménez, M; Estrada; Reyes-Chilpa, R; Kauffman, F C

    2001-11-01

    Calophyllum brasiliense, Lonchocarpus oaxacensis, and Lonchocarpus guatemalensis are used in Latin American folk medicine. Four natural xanthones, an acetylated derivative, and two coumarins were obtained from C. brasiliense. Two flavanones were extracted from L. oaxacensis and one chalcone from L guatemalensis. These compounds were tested as substrates and inhibitors for two recombinant sulfotransferases (SULTs) involved in the metabolism of many endogenous compounds and foreign chemicals. Assays were performed using recombinant phenolsulfotransferase (SULT1A1) and hydroxysteroidsulfotransferase (SULT2A1). Three of the five xanthones, one of the flavonoids and the coumarins tested were substrates for SULT1A1. None of the xanthones or the flavonoids were sulfonated by SULT2A1, whereas the coumarin mammea A/BA was a substrate for this enzyme. The natural xanthones reversibly inhibited SULT1A1 with IC50 values ranging from 1.6 to 7 microM whereas much higher amounts of these compounds were required to inhibit SULT2A1 (IC50 values of 26-204 microM). The flavonoids inhibited SULT1A1 with IC50 values ranging from 9.5 to 101 microM, which compared with amounts needed to inhibit SULT2A1 (IC50 values of 11 to 101 microM). Both coumarins inhibited SULT1A1 with IC50 values of 47 and 185 pM, and SULT2A1 with IC50 values of 16 and 31 microM. The acetylated xanthone did not inhibit either SULT1AI or SULT2A1 activity. Rotenone from a commercial source had potency comparable to that of the flavonoids isolated from Lonchocarpus for inhibiting both SULTs. The potency of this inhibition depends on the position and number of hydroxyls. The results indicate that SULT1A1, but not SULT2A1, is highly sensitive to inhibition by xanthones. Conversely, SULT2A1 is 3-6 times more sensitive to coumarins than SULT1A1. The flavonoids are non-specific inhibitors of the two SULTs. Collectively, the results suggest that these types of natural products have the potential for important

  20. Aldehyde dehydrogenase 1A1 in stem cells and cancer

    PubMed Central

    Tomita, Hiroyuki; Tanaka, Kaori; Tanaka, Takuji; Hara, Akira

    2016-01-01

    The human genome contains 19 putatively functional aldehyde dehydrogenase (ALDH) genes, which encode enzymes critical for detoxification of endogenous and exogenous aldehyde substrates through NAD(P)+-dependent oxidation. ALDH1 has three main isotypes, ALDH1A1, ALDH1A2, and ALDH1A3, and is a marker of normal tissue stem cells (SC) and cancer stem cells (CSC), where it is involved in self-renewal, differentiation and self-protection. Experiments with murine and human cells indicate that ALDH1 activity, predominantly attributed to isotype ALDH1A1, is tissue- and cancer-specific. High ALDH1 activity and ALDH1A1 overexpression are associated with poor cancer prognosis, though high ALDH1 and ALDH1A1 levels do not always correlate with highly malignant phenotypes and poor clinical outcome. In cancer therapy, ALDH1A1 provides a useful therapeutic CSC target in tissue types that normally do not express high levels of ALDH1A1, including breast, lung, esophagus, colon and stomach. Here we review the functions and mechanisms of ALDH1A1, the key ALDH isozyme linked to SC populations and an important contributor to CSC function in cancers, and we outline its potential in future anticancer strategies. PMID:26783961

  1. Effect of DNA methylation profile on OATP3A1 and OATP4A1 transcript levels in colorectal cancer.

    PubMed

    Rawłuszko-Wieczorek, Agnieszka Anna; Horst, Nikodem; Horbacka, Karolina; Bandura, Artur Szymon; Świderska, Monika; Krokowicz, Piotr; Jagodziński, Paweł Piotr

    2015-08-01

    Epidemiological studies indicate that 17β-estradiol (E2) prevents colorectal cancer (CRC). Organic anion transporting polypeptides (OATPs) are involved in the cellular uptake of various endogenous and exogenous substrates, including hormone conjugates. Because transfer of estrone sulfate (E1-S) can contribute to intra-tissue conversion of estrone to the biologically active form -E2, it is evident that the expression patterns of OATPs may be relevant to the analysis of CRC incidence and therapy. We therefore evaluated DNA methylation and transcript levels of two members of the OATP family, OATP3A1 and OATP4A1, that may be involved in E1-S transport in colorectal cancer patients. We detected a significant reduction in OATP3A1 and a significant increase in OATP4A1 mRNA levels in cancerous tissue, compared with histopathologically unchanged tissue (n=103). Moreover, we observed DNA hypermethylation in the OATP3A1 promoter region in a small subset of CRC patients and in HCT116 and Caco-2 colorectal cancer cell lines. We also observed increased OATP3A1 transcript following treatment with 5-aza-2-deoxycytidine and sodium butyrate. The OATP4A1 promoter region was hypomethylated in analyzed tissues and CRC cell lines and was not affected by these treatments. Our results suggest a potential mechanism for OATP3A1 downregulation that involves DNA methylation during colorectal carcinogenesis. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  2. Temporal trends of hemoglobin A1c testing.

    PubMed

    Pivovarov, Rimma; Albers, David J; Hripcsak, George; Sepulveda, Jorge L; Elhadad, Noémie

    2014-01-01

    The study of utilization patterns can quantify potential overuse of laboratory tests and find new ways to reduce healthcare costs. We demonstrate the use of distributional analytics for comparing electronic health record (EHR) laboratory test orders across time to diagnose and quantify overutilization. We looked at hemoglobin A1c (HbA1c) testing across 119,000 patients and 15 years of hospital records. We examined the patterns of HbA1c ordering before and after the publication of the 2002 American Diabetes Association guidelines for HbA1c testing. We conducted analyses to answer three questions. What are the patterns of HbA1c ordering? Do HbA1c orders follow the guidelines with respect to frequency of measurement? If not, how and why do they depart from the guidelines? The raw number of HbA1c orderings has steadily increased over time, with a specific increase in low-measurement orderings (<6.5%). There is a change in ordering pattern following the 2002 guideline (p<0.001). However, by comparing ordering distributions, we found that the changes do not reflect the guidelines and rather exhibit a new practice of rapid-repeat testing. The rapid-retesting phenomenon does not follow the 2009 guidelines for diabetes diagnosis either, illustrated by a stratified HbA1c value analysis. Results suggest HbA1c test overutilization, and contributing factors include lack of care coordination, unexpected values prompting retesting, and point-of-care tests followed by confirmatory laboratory tests. We present a method of comparing ordering distributions in an EHR across time as a useful diagnostic approach for identifying and assessing the trend of inappropriate use over time. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  3. Ranolazine and Its Effects on Hemoglobin A1C.

    PubMed

    Greiner, Lindsey; Hurren, Kathryn; Brenner, Michael

    2016-05-01

    To review the antihyperglycemic effect of ranolazine in type 2 diabetes mellitus (T2DM). An EMBASE search was conducted between January 1966 through December 2015 using the search termsranolazine, diabetes, andhemoglobin A1C(A1C). Additional references were identified from a review of literature citations. A search of clinicaltrials.gov was conducted to identify unpublished studies assessing ranolazine in diabetes. All English-language observational and randomized controlled trials assessing the effects of ranolazine on A1C were evaluated. Four published and 3 unpublished trials were identified. In all except 1 study, ranolazine 750 to 1000 mg twice daily was associated with a statistically significant decrease in A1C compared with placebo (placebo-corrected change in A1C: -0.28 to -0.7). In the trial in which a significant difference was not observed, patients assigned to ranolazine received a lower maintenance metformin dose compared with patients not assigned to ranolazine. A greater percentage of patients randomized to ranolazine achieved an A1C<7% compared with the placebo group (41.2%-59% vs 25.7%-49%). Ranolazine was not associated with an increase in the incidence of hypoglycemia and was well tolerated overall. The mechanism for lowering of A1C has not been determined. Ranolazine therapy may decrease A1C among patients with T2DM without an increase in hypoglycemia. For patients with T2DM and chronic stable angina, ranolazine may be of use given its utility in cardiovascular disease and benefit in A1C lowering. © The Author(s) 2016.

  4. The correlation of hemoglobin A1c to blood glucose.

    PubMed

    Sikaris, Ken

    2009-05-01

    The understanding that hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes. Even in making such a statement, we speak of "average blood glucose" as though "blood glucose" were itself a simple idea. When we consider all the blood glucose forms-arterial versus venous versus capillary, whole blood versus serum versus fluoride-preserved plasma, fasting versus nonfasting-we can start to see that this is not a simple issue. Nevertheless, it seems as though HbA1c correlates to any single glucose measurement. Having more than one measurement and taking those measurements in the preceding month improves the correlation further. In particular, by having glucose measurements that reflect both the relatively lower overnight glucose levels and measurements that reflect the postprandial peaks improves not only our ability to manage diabetes patients, but also our understanding of how HbA1c levels are determined. Modern continuous glucose monitoring (CGM) devices may take thousands of glucose results over a week. Several studies have shown that CGM glucose averages account for the vast proportion of the variation of HbA1c. The ability to relate HbA1c to average glucose may become a popular method for reporting HbA1c, eliminating current concerns regarding differences in HbA1c standardization. Hemoglobin A1c expressed as an average glucose may be more understandable to patients and improve not only their understanding, but also their ability to improve their diabetes management. 2009 Diabetes Technology Society.

  5. The Correlation of Hemoglobin A1c to Blood Glucose

    PubMed Central

    Sikaris, Ken

    2009-01-01

    The understanding that hemoglobin A1c (HbA1c) represents the average blood glucose level of patients over the previous 120 days underlies the current management of diabetes. Even in making such a statement, we speak of “average blood glucose” as though “blood glucose” were itself a simple idea. When we consider all the blood glucose forms—arterial versus venous versus capillary, whole blood versus serum versus fluoride-preserved plasma, fasting versus nonfasting—we can start to see that this is not a simple issue. Nevertheless, it seems as though HbA1c correlates to any single glucose measurement. Having more than one measurement and taking those measurements in the preceding month improves the correlation further. In particular, by having glucose measurements that reflect both the relatively lower overnight glucose levels and measurements that reflect the postprandial peaks improves not only our ability to manage diabetes patients, but also our understanding of how HbA1c levels are determined. Modern continuous glucose monitoring (CGM) devices may take thousands of glucose results over a week. Several studies have shown that CGM glucose averages account for the vast proportion of the variation of HbA1c. The ability to relate HbA1c to average glucose may become a popular method for reporting HbA1c, eliminating current concerns regarding differences in HbA1c standardization. Hemoglobin A1c expressed as an average glucose may be more understandable to patients and improve not only their understanding, but also their ability to improve their diabetes management. PMID:20144279

  6. Assessing respiratory pathogen communities in bighorn sheep populations: Sampling realities, challenges, and improvements

    PubMed Central

    Edwards, William H.; Jennings-Gaines, Jessica E.; Killion, Halcyon J.; Wood, Mary E.; McWhirter, Douglas E.; Paterson, J. Terrill; Proffitt, Kelly M.; Almberg, Emily S.; White, P. J.; Rotella, Jay J.; Garrott, Robert A.

    2017-01-01

    Respiratory disease has been a persistent problem for the recovery of bighorn sheep (Ovis canadensis), but has uncertain etiology. The disease has been attributed to several bacterial pathogens including Mycoplasma ovipneumoniae and Pasteurellaceae pathogens belonging to the Mannheimia, Bibersteinia, and Pasteurella genera. We estimated detection probability for these pathogens using protocols with diagnostic tests offered by a fee-for-service laboratory and not offered by a fee-for-service laboratory. We conducted 2861 diagnostic tests on swab samples collected from 476 bighorn sheep captured across Montana and Wyoming to gain inferences regarding detection probability, pathogen prevalence, and the power of different sampling methodologies to detect pathogens in bighorn sheep populations. Estimated detection probability using fee-for-service protocols was less than 0.50 for all Pasteurellaceae and 0.73 for Mycoplasma ovipneumoniae. Non-fee-for-service Pasteurellaceae protocols had higher detection probabilities, but no single protocol increased detection probability of all Pasteurellaceae pathogens to greater than 0.50. At least one protocol resulted in an estimated detection probability of 0.80 for each pathogen except Mannheimia haemolytica, for which the highest detection probability was 0.45. In general, the power to detect Pasteurellaceae pathogens at low prevalence in populations was low unless many animals were sampled or replicate samples were collected per animal. Imperfect detection also resulted in low precision when estimating prevalence for any pathogen. Low and variable detection probabilities for respiratory pathogens using live-sampling protocols may lead to inaccurate conclusions regarding pathogen community dynamics and causes of bighorn sheep respiratory disease epizootics. We recommend that agencies collect multiples samples per animal for Pasteurellaceae detection, and one sample for Mycoplasma ovipneumoniae detection from at least 30

  7. Assessing respiratory pathogen communities in bighorn sheep populations: Sampling realities, challenges, and improvements.

    PubMed

    Butler, Carson J; Edwards, William H; Jennings-Gaines, Jessica E; Killion, Halcyon J; Wood, Mary E; McWhirter, Douglas E; Paterson, J Terrill; Proffitt, Kelly M; Almberg, Emily S; White, P J; Rotella, Jay J; Garrott, Robert A

    2017-01-01

    Respiratory disease has been a persistent problem for the recovery of bighorn sheep (Ovis canadensis), but has uncertain etiology. The disease has been attributed to several bacterial pathogens including Mycoplasma ovipneumoniae and Pasteurellaceae pathogens belonging to the Mannheimia, Bibersteinia, and Pasteurella genera. We estimated detection probability for these pathogens using protocols with diagnostic tests offered by a fee-for-service laboratory and not offered by a fee-for-service laboratory. We conducted 2861 diagnostic tests on swab samples collected from 476 bighorn sheep captured across Montana and Wyoming to gain inferences regarding detection probability, pathogen prevalence, and the power of different sampling methodologies to detect pathogens in bighorn sheep populations. Estimated detection probability using fee-for-service protocols was less than 0.50 for all Pasteurellaceae and 0.73 for Mycoplasma ovipneumoniae. Non-fee-for-service Pasteurellaceae protocols had higher detection probabilities, but no single protocol increased detection probability of all Pasteurellaceae pathogens to greater than 0.50. At least one protocol resulted in an estimated detection probability of 0.80 for each pathogen except Mannheimia haemolytica, for which the highest detection probability was 0.45. In general, the power to detect Pasteurellaceae pathogens at low prevalence in populations was low unless many animals were sampled or replicate samples were collected per animal. Imperfect detection also resulted in low precision when estimating prevalence for any pathogen. Low and variable detection probabilities for respiratory pathogens using live-sampling protocols may lead to inaccurate conclusions regarding pathogen community dynamics and causes of bighorn sheep respiratory disease epizootics. We recommend that agencies collect multiples samples per animal for Pasteurellaceae detection, and one sample for Mycoplasma ovipneumoniae detection from at least 30

  8. Microbial diversity and dynamics during the production of May bryndza cheese.

    PubMed

    Pangallo, Domenico; Saková, Nikoleta; Koreňová, Janka; Puškárová, Andrea; Kraková, Lucia; Valík, Lubomír; Kuchta, Tomáš

    2014-01-17

    Diversity and dynamics of microbial cultures were studied during the production of May bryndza cheese, a traditional Slovak cheese produced from unpasteurized ewes' milk. Quantitative culture-based data were obtained for lactobacilli, lactococci, total mesophilic aerobic counts, coliforms, E. coli, staphylococci, coagulase-positive staphylococci, yeasts, fungi and Geotrichum spp. in ewes' milk, curd produced from it and ripened for 0 - 10 days, and in bryndza cheese produced from the curd, in three consecutive batches. Diversity of prokaryotes and eukaryotes in selected stages of the production was studied by non-culture approach based on amplification of 16S rDNA and internal transcribed spacer region, coupled to denaturing gradient gel electrophoresis and sequencing. The culture-based data demonstrated an overall trend of growth of the microbial population contributing to lactic acid production and to ripening of the cheese, lactobacilli, lactococci and Geotrichum spp. growing up to densities of 10(8) CFU/g, 10(9) CFU/g and 10(5) CFU/g, respectively, in all three consecutive batches of bryndza cheese. The diversity of bacteria encompassed Acinetobacter calcoaceticus, Acinetobacter guillouiae, Acinetobacter sp., Acinetobacter johnsonii, Citrobacter braakii, Clostridium bartlettii, Corynebacterium callunae, Corynebacterium maris, Enterobacter aerogenes, Enterobacter asburiae, Enterobacter hormaechei, Enterococcus faecium, Enterococcus pallens, Escherichia coli, Haemophilus haemolyticus, Hafnia alvei, Kluyvera cryocrescens, Lactobacillus helveticus, Lactococcus garvieae, Lc. lactis subsp. cremoris, Lc. lactis subsp. lactis, "Leuconostoc garlicum", Mannheimia glucosida, Mannheimia haemolytica, Pseudomonas sp., Ps. fluorescens, "Ps. reactans", Raoultella ornithinolytica, R. terrigena, "Rothia arfidiae", Staphylococcus aureus, Staph. epidermidis, Staph. felis, Staph. pasteuri, Staph. sciuri, Staph. xylosus, Streptococcus parauberis, Str. thermophilus and Variovorax

  9. Human aldehyde dehydrogenase 3A1 (ALDH3A1): biochemical characterization and immunohistochemical localization in the cornea.

    PubMed Central

    Pappa, Aglaia; Estey, Tia; Manzer, Rizwan; Brown, Donald; Vasiliou, Vasilis

    2003-01-01

    ALDH3A1 (aldehyde dehydrogenase 3A1) is expressed at high concentrations in the mammalian cornea and it is believed that it protects this vital tissue and the rest of the eye against UV-light-induced damage. The precise biological function(s) and cellular distribution of ALDH3A1 in the corneal tissue remain to be elucidated. Among the hypotheses proposed for ALDH3A1 function in cornea is detoxification of aldehydes formed during UV-induced lipid peroxidation. To investigate in detail the biochemical properties and distribution of this protein in the human cornea, we expressed human ALDH3A1 in Sf9 insect cells using a baculovirus vector and raised monoclonal antibodies against ALDH3A1. Recombinant ALDH3A1 protein was purified to homogeneity with a single-step affinity chromatography method using 5'-AMP-Sepharose 4B. Human ALDH3A1 demonstrated high substrate specificity for medium-chain (6 carbons and more) saturated and unsaturated aldehydes, including 4-hydroxy-2-nonenal, which are generated by the peroxidation of cellular lipids. Short-chain aliphatic aldehydes, such as acetaldehyde, propionaldehyde and malondialdehyde, were found to be very poor substrates for human ALDH3A1. In addition, ALDH3A1 metabolized glyceraldehyde poorly and did not metabolize glucose 6-phosphate, 6-phosphoglucono-delta-lactone and 6-phosphogluconate at all, suggesting that this enzyme is not involved in either glycolysis or the pentose phosphate pathway. Immunohistochemistry in human corneas, using the monoclonal antibodies described herein, revealed ALDH3A1 expression in epithelial cells and stromal keratocytes, but not in endothelial cells. Overall, these cumulative findings support the metabolic function of ALDH3A1 as a part of a corneal cellular defence mechanism against oxidative damage caused by aldehydic products of lipid peroxidation. Both recombinant human ALDH3A1 and the highly specific monoclonal antibodies described in the present paper may prove to be useful in probing

  10. Prevalence of normoglycemic, prediabetic and diabetic A1c levels

    PubMed Central

    Aponte, Judith

    2013-01-01

    AIM: To investigate normoglycemic, prediabetic and diabetic A1c levels in those with prediabetes; and prediabetic and diabetic A1c levels in those with non-prediabetes. METHODS: The National Health and Nutritional Examination Survey (NHANES) 2007-2008 and NHANES 2009-2010 were utilized to examine and compare trends and differences among five different ethnic groups (Mexican Americans, Other Hispanics, Non-Hispanic Whites, Non-Hispanic Blacks, Other/Multi-racials) with normoglycemic, prediabetic and diabetic A1c levels with self-reported prediabetes and prediabetic and diabetic A1c levels in those with self-reported non-prediabetes. Sample participants of the five ethnic groups were limited to those 20 years of age and older, who had completed the diabetes questionnaire and had A1c measured. Descriptive statistics were computed for all variables. χ2 were performed on all five ethnic groups to examine significant differences of normoglycemic, prediabetic and diabetic A1c levels in those with self-reported prediabetes, and prediabetic and diabetic A1c levels in those with self-reported non-prediabetes. RESULTS: This study demonstrates that of the five different ethnic groups from NHANES 2007-2008 to NHANES 2009-2010, Non-Hispanic Whites (6.5% increase) and Non-Hispanic Blacks (0.2% increase) were the only two groups with an increase in the number of self-reported prediabetes. Although the overall percentage of Mexican Americans who self-reported prediabetes had remained the same (5%) from NHANES 2007-2008 to NHANES 2009-2010, χ2 analysis showed significant differences when examining the different ranges of A1c levels (normoglycemic, prediabetic and diabetic). Among Mexican Americans who self-reported prediabetes, normoglycemic (P = 0.0001) and diabetic (P = 0.0001) A1c levels from NHANES 2007-2008 to NHANES 2009-2010. For Non-Hispanic Whites who self-reported prediabetes, prediabetic (P = 0.0222); and diabetic (P ≤ 0.0001) A1c levels from NHANES 2007-2008 to

  11. Plasma apolipoprotein A1 as a biomarker for Parkinson disease.

    PubMed

    Qiang, Judy K; Wong, Yvette C; Siderowf, Andrew; Hurtig, Howard I; Xie, Sharon X; Lee, Virginia M-Y; Trojanowski, John Q; Yearout, Dora; B Leverenz, James; Montine, Thomas J; Stern, Matt; Mendick, Susan; Jennings, Danna; Zabetian, Cyrus; Marek, Ken; Chen-Plotkin, Alice S

    2013-07-01

    To identify plasma-based biomarkers for Parkinson disease (PD) risk. In a discovery cohort of 152 PD patients, plasma levels of 96 proteins were measured by multiplex immunoassay; proteins associated with age at PD onset were identified by linear regression. Findings from discovery screening were then assessed in a second cohort of 187 PD patients, using a different technique. Finally, in a third cohort of at-risk, asymptomatic individuals enrolled in the Parkinson's Associated Risk Study (PARS, n = 134), plasma levels of the top candidate biomarker were measured, and dopamine transporter (DAT) imaging was performed, to evaluate the association of plasma protein levels with dopaminergic system integrity. One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1; p = 0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards, p < 0.001, hazard ratio = 0.742). The association between plasma ApoA1 levels and age at PD onset was replicated in an independent cohort of PD patients (p < 0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p = 0.037). Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk. Copyright © 2013 American Neurological Association.

  12. Hemoglobin A1c predicts healing rate in diabetic wounds.

    PubMed

    Christman, Andrea L; Selvin, Elizabeth; Margolis, David J; Lazarus, Gerald S; Garza, Luis A

    2011-10-01

    Lower-extremity wounds are a major complication of diabetes. Hemoglobin A1c (HbA1c) reflects glycemia over 2-3 months and is the standard measure used to monitor glycemia in diabetic patients, but results from studies have not shown a consistent association of HbA1c with wound healing. We hypothesized that elevated HbA1c would be most associated with poor wound healing. To test this hypothesis, we conducted a retrospective cohort study of 183 diabetic individuals treated at the Johns Hopkins Wound Center. Our primary outcome was wound-area healing rate (cm(2) per day). Calibrated tracings of digital images were used to measure wound area. We estimated coefficients for healing rate using a multiple linear regression model controlling for clustering of wounds within individuals and other common clinic variables. The study population was 45% female and 41% African American, with a mean age of 61 years. Mean HbA1c was 8.0%, and there were 2.3 wounds per individual (310 wounds total). Of all measures assessed, only HbA1c was significantly associated with wound-area healing rate. In particular, for each 1.0% point increase in HbA1c, the daily wound-area healing rate decreased by 0.028 cm(2) per day (95% confidence interval: 0.003, 0.0054, P = 0.027). Our results suggest that glycemia, as assessed by HbA1c, may be an important biomarker in predicting wound-healing rate in diabetic patients.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub.

  13. A 1K Shadow RAM for circumvention applications

    SciTech Connect

    Murray, J.R.

    1991-01-01

    A 1K bit Shadow RAM has been developed for storage of critical data in a high transient radiation environment. The circuit includes a 1K bit (128 {times} 8) static RAM with two non-volatile (NV) shadows. The NV shadows are used to back-up the data in the static RAM allowing the circuit to be powered down during transient radiation without losing critical data. This paper will describe the circuit's operation and characterization results.

  14. Plasma Apolipoprotein A1 as a Biomarker for Parkinson's Disease

    PubMed Central

    Qiang, Judy K.; Wong, Yvette C.; Siderowf, Andrew; Hurtig, Howard I.; Xie, Sharon X.; Lee, Virginia M.-Y.; Trojanowski, John Q.; Yearout, Dora; Leverenz, James; Montine, Thomas J.; Stern, Matt; Mendick, Susan; Jennings, Danna; Zabetian, Cyrus; Marek, Ken; Chen-Plotkin, Alice S.

    2013-01-01

    Objective To identify plasma-based biomarkers for Parkinson's Disease (PD) risk. Methods In a discovery cohort of 152 PD patients, plasma levels of 96 proteins were measured by multiplex immunoassay; proteins associated with age at PD onset were identified by linear regression. Findings from discovery screening were then assessed in a second cohort of 187 PD patients, using a different technique. Finally, in a third cohort of at-risk, asymptomatic individuals enrolled in the Parkinson's Associated Risk Study (PARS, n=134), plasma levels of the top candidate biomarker were measured, and dopamine transporter (DAT) imaging performed, to evaluate the association of plasma protein levels with dopaminergic system integrity. Results One of the best candidate protein biomarkers to emerge from discovery screening was apolipoprotein A1 (ApoA1, p=0.001). Low levels of ApoA1 correlated with earlier PD onset, with a 26% decrease in risk of developing PD associated with each tertile increase in ApoA1 (Cox proportional hazards p<0.001, hazard ratio=0.742). The association between plasma ApoA1 levels and age at PD onset replicated in an independent cohort of PD patients (p<0.001). Finally, in the PARS cohort of high-risk, asymptomatic subjects, lower plasma levels of ApoA1 were associated with greater putaminal DAT deficit (p=0.037). Interpretation Lower ApoA1 levels correlate with dopaminergic system vulnerability in symptomatic PD patients and in asymptomatic individuals with physiological reductions in dopamine transporter density consistent with prodromal PD. Plasma ApoA1 may be a new biomarker for PD risk. PMID:23447138

  15. COL4A1 mutation in preterm intraventricular hemorrhage.

    PubMed

    Bilguvar, Kaya; DiLuna, Michael L; Bizzarro, Matthew J; Bayri, Yasar; Schneider, Karen C; Lifton, Richard P; Gunel, Murat; Ment, Laura R

    2009-11-01

    Intraventricular hemorrhage is a common complication of preterm infants. Mutations in the type IV procollagen gene, COL4A1, are associated with cerebral small vessel disease with hemorrhage in adults and fetuses. We report a rare variant in COL4A1 associated with intraventricular hemorrhage in dizygotic preterm twins. These results expand the spectrum of diseases attributable to mutations in type IV procollagens.

  16. CYP24A1 — EDRN Public Portal

    Cancer.gov

    The CYP24A1 protein is a member of the cytochrome P450 superfamily of enzymes. The cytochrome P450 proteins are monooxygenases which catalyze many reactions involved in drug metabolism and synthesis of cholesterol, steroids and other lipids. CYP24A1 is involved in maintaining calcium homeostasis and catalyzes the NADPH-dependent 24-hydroxylation of calcidiol (25-hydroxyvitamin D3) and calcitriol (1-alpha,25-dihydroxyvitamin D3). Several different isoforms exist, encoded by alternatively spliced transcript variants.

  17. ISS 7A.1 Flight Control Team Photo in BFCR

    NASA Image and Video Library

    2001-08-17

    JSC2001-02225 (17 August 2001) --- The members of the STS-105/ISS 7A.1 Orbit 2 team pose for a group portrait in the International Space Station (ISS) flight control room (BFCR) in Houston’s Mission Control Center (MCC). Orbit 2 flight director Rick LaBrode (front right) holds the STS-105 mission logo, and Astronaut Joan E. Higginbotham, ISS spacecraft communicator (CAPCOM), holds the ISS 7A.1 mission logo.

  18. 26 CFR 31.6402(a)-1 - Credits or refunds.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false Credits or refunds. 31.6402(a)-1 Section 31... Revenue Code of 1954) § 31.6402(a)-1 Credits or refunds. (a) In general. For regulations under section 6402 of special application to credits or refunds of employment taxes, see §§ 31.6402(a)-2, 31.6402(a...

  19. Production of a_1 in heavy meson decays

    NASA Astrophysics Data System (ADS)

    Wang, Wei; Zhao, Zhen-Xing

    2016-02-01

    In this work, we study various decays of heavy B / D mesons into the a_1(1260), based on the form factors derived in different nonperturbative or factorization approaches. These decay modes are helpful to explore the dynamics in the heavy to light transitions. Meanwhile they can also provide insights to a newly discovered state, the a_1(1420) with I^G(J^{PC})= 1^-(1^{++}) observed in the π ^+ f_0(980) final state in the π ^-p→ π ^+π ^-π ^- p process. Available theoretical explanations include tetraquark or rescattering effects due to a_1(1260) decays. If the a_1(1420) were induced by the rescattering, its production rates are completely determined by those of the a_1(1260). Our numerical results for decays into the a_1(1260) indicate that there is a promising prospect to study these decays on experiments including BES-III, LHCb, Babar, Belle, and CLEO-c, the forthcoming Super-KEKB factory and the under-design Circular Electron-Positron Collider.

  20. Respirable coal dust particles modify cytochrome P4501A1 (CYP1A1) expression in rat alveolar cells.

    PubMed

    Ghanem, Mohamed M; Porter, Dale; Battelli, Lori A; Vallyathan, Val; Kashon, Michael L; Ma, Jane Y; Barger, Mark W; Nath, Joginder; Castranova, Vincent; Hubbs, Ann F

    2004-08-01

    Cytochrome P4501A1 (CYP1A1) metabolizes polycyclic aromatic hydrocarbons in cigarette smoke to DNA-binding reactive intermediates associated with carcinogenesis. Epidemiologic studies indicate that the majority of coal miners are smokers but have a lower risk of lung cancer than other smokers. We hypothesized that coal dust (CD) exposure modifies pulmonary carcinogenesis by altering CYP1A1 induction. Therefore, male Sprague Dawley rats were intratracheally instilled with 2.5, 10, 20, or 40 mg CD/rat or vehicle (saline); and 11 d later, pulmonary CYP1A1 was induced by intraperitoneal injection of beta-naphthoflavone (BNF; 50 mg/kg). Fourteen days after CD exposure, CYP1A1 protein and activity were measured by Western blot and 7-ethoxyresorufin-O-deethylase activity, respectively. CYP1A1 and the alveolar type II markers, cytokeratins 8/18, were localized and quantified in lung sections by dual immunofluorescence with morphometry. The area of CYP1A1 expression in alveolar septa and alveolar type II cells in response to BNF was reduced by exposure to 20 or 40 mg CD compared with BNF alone. CD exposure significantly inhibited BNF-induced 7-ethoxyresorufin-O-deethylase activity in a dose-responsive manner. By Western blot, induction of CYP1A1 protein by BNF was significantly reduced by 40 mg CD compared with BNF alone. These findings indicate that CD decreases BNF-induced CYP1A1 protein expression and activity in the lung.

  1. Insufficient Sensitivity of Hemoglobin A1C (A1C) Determination in Diagnosis or Screening of Early Diabetic States

    PubMed Central

    Fajans, Stefan S.; Herman, William H.; Oral, Elif A.

    2010-01-01

    An International Expert Committee made recommendations for using the hemoglobin A1C (A1C) assay as the preferred method for diagnosis of diabetes in nonpregnant individuals. A concentration of ≥ 6.5% was considered as diagnostic. It is the aim of this study to compare the sensitivity of A1C with that of plasma glucose concentrations in subjects with early diabetes or IGT. We chose two groups of subjects who had A1C of ≤ 6.4%. The first group of 89 subjects had family histories of diabetes (MODY or T2DM) and had OGTT and A1C determinations. They included 36 subjects with diabetes or IGT and 53 with normal OGTT. The second group of 58 subjects was screened for diabetes in our Diabetes Clinic by FPG or 2HPG or OGTT and A1C and similar comparisons were made. Subjects with diabetes or IGT, including those with fasting hyperglycemia, had A1C ranging from 5.0 – 6.4%, mean 5.8%. The subjects with normal OGTT had A1C of 4.2 – 6.3%, mean 5.4% or 5.5% for the two groups. A1C may be in the normal range in subjects with diabetes or IGT, including those with fasting hyperglycemia. Approximately one third of subjects with early diabetes and IGT have A1C <5.7%, the cut-point that ADA recommends as indicating the onset of risk of developing diabetes in the future. The results of our study are similar to those obtained by a large Dutch epidemiological study. If our aim is to recognize early diabetic states to apply effective prophylactic procedures to prevent or delay progression to more severe diabetes, A1C is not sufficiently sensitive or reliable for diagnosis of diabetes or IGT. A combination of A1C and plasma glucose determinations, where necessary, are recommended for diagnosis or screening of diabetes or IGT. PMID:20723948

  2. Structured literature review of responses of cattle to viral and bacterial pathogens causing bovine respiratory disease complex.

    PubMed

    Grissett, G P; White, B J; Larson, R L

    2015-01-01

    Bovine respiratory disease (BRD) is an economically important disease of cattle and continues to be an intensely studied topic. However, literature summarizing the time between pathogen exposure and clinical signs, shedding, and seroconversion is minimal. A structured literature review of the published literature was performed to determine cattle responses (time from pathogen exposure to clinical signs, shedding, and seroconversion) in challenge models using common BRD viral and bacterial pathogens. After review a descriptive analysis of published studies using common BRD pathogen challenge studies was performed. Inclusion criteria were single pathogen challenge studies with no treatment or vaccination evaluating outcomes of interest: clinical signs, shedding, and seroconversion. Pathogens of interest included: bovine viral diarrhea virus (BVDV), bovine herpesvirus type 1 (BHV-1), parainfluenza-3 virus, bovine respiratory syncytial virus, Mannheimia haemolytica, Mycoplasma bovis, Pastuerella multocida, and Histophilus somni. Thirty-five studies and 64 trials were included for analysis. The median days to the resolution of clinical signs after BVDV challenge was 15 and shedding was not detected on day 12 postchallenge. Resolution of BHV-1 shedding resolved on day 12 and clinical signs on day 12 postchallenge. Bovine respiratory syncytial virus ceased shedding on day 9 and median time to resolution of clinical signs was on day 12 postchallenge. M. haemolytica resolved clinical signs 8 days postchallenge. This literature review and descriptive analysis can serve as a resource to assist in designing challenge model studies and potentially aid in estimation of duration of clinical disease and shedding after natural pathogen exposure. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  3. Anti-Inflammatory Benefits of Antibiotic-Induced Neutrophil Apoptosis: Tulathromycin Induces Caspase-3-Dependent Neutrophil Programmed Cell Death and Inhibits NF-κB Signaling and CXCL8 Transcription▿

    PubMed Central

    Fischer, Carrie D.; Beatty, Jennifer K.; Zvaigzne, Cheryl G.; Morck, Douglas W.; Lucas, Merlyn J.; Buret, A. G.

    2011-01-01

    Clearance of apoptotic neutrophils is a central feature of the resolution of inflammation. Findings indicate that immuno-modulation and induction of neutrophil apoptosis by macrolide antibiotics generate anti-inflammatory benefits via mechanisms that remain obscure. Tulathromycin (TUL), a new antimicrobial agent for bovine respiratory disease, offers superior clinical efficacy for reasons not fully understood. The aim of this study was to identify the immuno-modulating effects of tulathromycin and, in this process, to establish tulathromycin as a new model for characterizing the novel anti-inflammatory properties of antibiotics. Bronchoalveolar lavage specimens were collected from Holstein calves 3 and 24 h postinfection, challenged intratracheally with live Mannheimia haemolytica (2 × 107 CFU), and treated with vehicle or tulathromycin (2.5 mg/kg body weight). Terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling (TUNEL) staining and enzyme-linked immunosorbent assay (ELISA) revealed that tulathromycin treatment significantly increased leukocyte apoptosis and reduced levels of proinflammatory leukotriene B4 in M. haemolytica-challenged calves. In vitro, tulathromycin concentration dependently induced apoptosis in freshly isolated bovine neutrophils from healthy steers in a capase-3-dependent manner but failed to induce apoptosis in bovine fibroblasts, epithelial cells, and endothelial cells, as well as freshly isolated bovine blood monocytes and monocyte-derived macrophages. The proapoptotic effects of TUL were also, in part, drug specific; equimolar concentrations of penicillin G, oxytetracycline, and ceftiofur failed to cause apoptosis in bovine neutrophils. In addition, tulathromycin significantly reduced levels of phosphorylated IκBα, nuclear translocation of NF-κB p65, and mRNA levels of proinflammatory interleukin-8 in lipopolysaccharide (LPS)-stimulated bovine neutrophils. The findings illustrate novel mechanisms through which

  4. Bacterial ghosts as novel advanced drug delivery systems: antiproliferative activity of loaded doxorubicin in human Caco-2 cells.

    PubMed

    Paukner, Susanne; Kohl, Gudrun; Lubitz, Werner

    2004-01-08

    Systemic application of anticancer drugs often causes severe toxic side effects. To reduce the undesired effects, advanced drug delivery systems are needed which are based on specific cell targeting vehicles. In this study, bacterial ghosts from Mannheimia haemolytica were used for site-specific delivery of doxorubicin (DOX) to human colorectal adenocarcinoma cells (Caco-2). Bacterial ghosts are non-denatured envelopes of Gram-negative bacteria with fully intact surface structures for specific attachment to mammalian cells. The in vitro release profile of DOX-ghosts demonstrated that the loaded drug was non-covalently associated with the bacterial ghosts and that the drug delivery vehicles themselves represent a slow release system. Adherence studies showed that the M. haemolytica ghosts more efficiently than E. coli ghosts targeted the Caco-2 cells and released the loaded DOX within the cells. Cytotoxicity assays revealed that the DOX-ghosts exhibited potent antiproliferative activities on Caco-2 cells as the DOX associated with ghosts was two magnitude of orders more cytotoxic than free DOX provided in the medium at the same concentrations. Notably, a significant reduction in the cell viability was measured with DOX-ghosts at low DOX concentrations, which had no inhibitory effect when applied as free DOX after incubation for 16 h or when applied at higher concentrations for only 10 min to the cells. As the higher antiproliferative effects of DOX on Caco-2 cells were mediated by the specific drug targeting properties of the bacterial ghosts, the bacterial ghost system represents a novel platform for advanced drug delivery.

  5. Estimation of nasal shedding and seroprevalence of organisms known to be associated with bovine respiratory disease in Australian live export cattle.

    PubMed

    Moore, S Jo; O'Dea, Mark A; Perkins, Nigel; O'Hara, Amanda J

    2015-01-01

    The prevalence of organisms known to be associated with bovine respiratory disease (BRD) was investigated in cattle prior to export. A quantitative reverse transcription polymerase chain reaction assay was used to detect nucleic acids from the following viruses and bacteria in nasal swab samples: Bovine coronavirus (BoCV; Betacoronavirus 1), Bovine herpesvirus 1 (BoHV-1), Bovine viral diarrhea virus 1 (BVDV-1), Bovine respiratory syncytial virus (BRSV), Bovine parainfluenza virus 3 (BPIV-3), Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida. Between 2010 and 2012, nasal swabs were collected from 1,484 apparently healthy cattle destined for export to the Middle East and Russian Federation. In addition, whole blood samples from 334 animals were tested for antibodies to BoHV-1, BRSV, BVDV-1, and BPIV-3 using enzyme-linked immunosorbent assay. The nasal prevalence of BoCV at the individual animal level was 40.1%. The nasal and seroprevalence of BoHV-1, BRSV, BVDV-1, and BPIV-3 was 1.0% and 39%, 1.2% and 46%, 3.0% and 56%, and 1.4% and 87%, respectively. The nasal prevalence of H. somni, M. bovis, M. haemolytica, and P. multocida was 42%, 4.8%, 13.4%, and 26%, respectively. Significant differences in nasal and seroprevalence were detected between groups of animals from different geographical locations. The results of the current study provide baseline data on the prevalence of organisms associated with BRD in Australian live export cattle in the preassembly period. This data could be used to develop strategies for BRD prevention and control prior to loading. © 2014 The Author(s).

  6. The nasopharyngeal microbiota of feedlot cattle that develop bovine respiratory disease.

    PubMed

    Holman, Devin B; McAllister, Tim A; Topp, Edward; Wright, André-Denis G; Alexander, Trevor W

    2015-10-22

    Bovine respiratory disease is the major cause of morbidity and mortality in feedlot cattle. The objective of this study was to compare the nasopharyngeal bacterial microbiota of healthy cattle and cattle treated for BRD in a commercial feedlot setting using a high-density 16S rRNA gene microarray (Phylochip). Samples were taken from both groups of animals (n=5) at feedlot entry (day 0) and ≥60 days after placement. Cattle diagnosed with BRD had significantly less bacterial diversity and fewer OTUs in their nasopharynx at both sampling times. The predominant phyla in both groups were Proteobacteria and Firmicutes. The relative abundance of the phylum Actinobacteria was lower in cattle treated for BRD. At the family-level there was a greater relative abundance (P<0.05) of Micrococcaceae (day 0 only), Lachnospiraceae (≥60 days), Lactobacillaceae (day 0), and Bacillaceae (day 0) in healthy cattle compared to BRD-affected cattle. The community structure of the BRD-affected and healthy cattle were also significantly different from each other at both sampling times as measured using unweighted UniFrac distances. All entry samples of cattle diagnosed with BRD had 16S rRNA gene sequences representative of the BRD-associated bacteria Mannheimia haemolytica or Pasteurella multocida, although 3/5 healthy cattle were also positive for M. haemolytica at this time point. The results also indicate that the bovine nasopharyngeal microbiota is relatively unstable during the first 60 days in the feedlot. Copyright © 2015. Published by Elsevier B.V.

  7. Bighorn sheep pneumonia: sorting out the cause of a polymicrobial disease.

    PubMed

    Besser, Thomas E; Frances Cassirer, E; Highland, Margaret A; Wolff, Peregrine; Justice-Allen, Anne; Mansfield, Kristin; Davis, Margaret A; Foreyt, William

    2013-02-01

    Pneumonia of bighorn sheep (Ovis canadensis) is a dramatic disease of high morbidity and mortality first described more than 80 years ago. The etiology of the disease has been debated since its initial discovery, and at various times lungworms, Mannheimia haemolytica and other Pasteurellaceae, and Mycoplasma ovipneumoniae have been proposed as primary causal agents. A multi-factorial "respiratory disease complex" has also been proposed as confirmation of causation has eluded investigators. In this paper we review the evidence for each of the candidate primary agents with regard to causal criteria including strength of association, temporality, plausibility, experimental evidence, and analogy. While we find some degree of biological plausibility for all agents and strong experimental evidence for M. haemolytica, we demonstrate that of the alternatives considered, M. ovipneumoniae is the best supported by all criteria and is therefore the most parsimonious explanation for the disease. The strong but somewhat controversial experimental evidence implicating disease transmission from domestic sheep is consistent with this finding. Based on epidemiologic and microbiologic data, we propose that healthy bighorn sheep populations are naïve to M. ovipneumoniae, and that its introduction to susceptible bighorn sheep populations results in epizootic polymicrobial bacterial pneumonia often followed by chronic infection in recovered adults. If this hypothesized model is correct, efforts to control this disease by development or application of vectored vaccines to Pasteurellaceae are unlikely to provide significant benefits, whereas efforts to ensure segregation of healthy bighorn sheep populations from M. ovipneumoniae-infected reservoir hosts are crucial to prevention of new disease epizootics. It may also be possible to develop M. ovipneumoniae vaccines or other management strategies that could reduce the impact of this devastating disease in bighorn sheep. Copyright © 2012

  8. Whole-Genome Sequencing and Concordance Between Antimicrobial Susceptibility Genotypes and Phenotypes of Bacterial Isolates Associated with Bovine Respiratory Disease.

    PubMed

    Owen, Joseph R; Noyes, Noelle; Young, Amy E; Prince, Daniel J; Blanchard, Patricia C; Lehenbauer, Terry W; Aly, Sharif S; Davis, Jessica H; O'Rourke, Sean M; Abdo, Zaid; Belk, Keith; Miller, Michael R; Morley, Paul; Van Eenennaam, Alison L

    2017-09-07

    Extended laboratory culture and antimicrobial susceptibility testing timelines hinder rapid species identification and susceptibility profiling of bacterial pathogens associated with bovine respiratory disease, the most prevalent cause of cattle mortality in the United States. Whole-genome sequencing offers a culture-independent alternative to current bacterial identification methods, but requires a library of bacterial reference genomes for comparison. To contribute new bacterial genome assemblies and evaluate genetic diversity and variation in antimicrobial resistance genotypes, whole-genome sequencing was performed on bovine respiratory disease-associated bacterial isolates (Histophilus somni, Mycoplasma bovis, Mannheimia haemolytica, and Pasteurella multocida) from dairy and beef cattle. One hundred genomically distinct assemblies were added to the NCBI database, doubling the available genomic sequences for these four species. Computer-based methods identified 11 predicted antimicrobial resistance genes in three species, with none being detected in M. bovis While computer-based analysis can identify antibiotic resistance genes within whole-genome sequences (genotype), it may not predict the actual antimicrobial resistance observed in a living organism (phenotype). Antimicrobial susceptibility testing on 64 H. somni, M. haemolytica, and P. multocida isolates had an overall concordance rate between genotype and phenotypic resistance to the associated class of antimicrobials of 72.7% (P < 0.001), showing substantial discordance. Concordance rates varied greatly among different antimicrobial, antibiotic resistance gene, and bacterial species combinations. This suggests that antimicrobial susceptibility phenotypes are needed to complement genomically predicted antibiotic resistance gene genotypes to better understand how the presence of antibiotic resistance genes within a given bacterial species could potentially impact optimal bovine respiratory disease treatment

  9. The diverse chemistry of cytochrome P450 17A1 (P450c17, CYP17A1)

    PubMed Central

    Yoshimoto, Francis K.; Auchus, Richard J.

    2014-01-01

    The steroid hydroxylation and carbon-carbon bond cleavage activities of cytochrome P450 17A1 (CYP17A1) are responsible for the production of glucocorticoids and androgens, respectively. The inhibition of androgen synthesis is an important strategy to treat androgen-dependent prostate cancer. We discuss the different enzymatic activities towards the various substrates of CYP17A1, demonstrating its promiscuity. Additionally, a novel interhelical interaction is proposed between the F-G loop and the B′-helix to explain the 16α-hydroxylase activity of human CYP17A1 with progesterone as the substrate. The techniques used by biochemists to study this important enzyme are also summarized. PMID:25482340

  10. Mitochondrial haplogroup M9a1a1c1b is associated with hypoxic adaptation in the Tibetans.

    PubMed

    Li, Qian; Lin, Keqin; Sun, Hao; Liu, Shuyuan; Huang, Kai; Huang, Xiaoqin; Chu, Jiayou; Yang, Zhaoqing

    2016-12-01

    While hypoxic environment at high altitude remains a major challenge for travelers from low-altitude areas, Tibetans have adapted to the high-altitude environment. Mitochondria are the energy conversion and supplement centers in eukaryotic cells. In recent years, studies have found that the diversity of the mitochondrial genome may have a role in the adaptation to hypoxia in Tibetans. In this study, mitochondrial haplogroup classification and variant genotyping were performed in Tibetan and Han Chinese populations living at different altitudes. The frequencies of mitochondrial haplogroups B and M7 in the high-altitude population were significantly lower compared with those in the low-altitude population (P=0.003 and 0.029, respectively), whereas the frequencies of haplogroups G and M9a1a1c1b in the high-altitude group were significantly higher compared with those in the low-altitude group (P=0.01 and 0.002, respectively). The frequencies of T3394C and G7697A, which are the definition sites of haplogroup M9a1a1c1b, were significantly higher in the high-altitude group compared with that in the low-altitude group (P=0.012 and 0.02, respectively). Our results suggest that mitochondrial haplogroups B and M7 are associated with inadaptability to hypoxic environments, whereas haplogroups G and M9a1a1c1b may be associated with hypoxic adaptation. In particular, the T3394C and G7697A variants on haplogroup M9a1a1c1b may be the primary cause of adaptation to hypoxia.

  11. ON THE DISTRIBUTION OF VITAMINS A1 AND A2

    PubMed Central

    Wald, George

    1939-01-01

    The distribution of vitamins A1 and A2 has been determined in the eye tissues and livers of a number of fishes. The vitamins were differentiated by means of the antimony chloride reaction, which yields with A1 a band at 615–620 mµ and with A2 a band at about 696 mµ. In the retina the presence of vitamin A1 is diagnostic of the operation of a rhodopsin, and vitamin A2 of a porphyropsin cycle. The eye tissues of all permanently marine fishes examined, except the tautog, contain vitamin A1 alone. Those of all permanently freshwater fishes possess only vitamin A2. Those of all euryhaline (potentially migratory) fishes, except possibly the alewife, contain mixtures of both vitamins A, and always predominantly that one which ordinarily is associated with the environment in which the fish is spawned. These correlations extend in part to the liver oils, but most livers contain mixtures of both vitamins A, and occasionally in proportions the reverse of those in the eye tissues. The vitamin A configuration does not depend upon environmental circumstances, but is determined genetically. The transfer from vitamin A1 to A2 metabolism appears associated phylogenetically with migration of marine teleosts into fresh water. PMID:19873110

  12. Rare SLC1A1 variants in hot water epilepsy.

    PubMed

    Karan, Kalpita Rashimi; Satishchandra, P; Sinha, Sanjib; Anand, Anuranjan

    2017-03-21

    Hot water epilepsy is sensory epilepsy, wherein seizures are triggered by an unusual stimulus: contact with hot water. Although genetic factors contribute to the etiology of hot water epilepsy, molecular underpinnings of the disorder remain largely unknown. We aimed to identify the molecular genetic basis of the disorder by studying families with two or more of their members affected with hot water epilepsy. Using a combination of genome-wide linkage mapping and whole exome sequencing, a missense variant was identified in SLC1A1 in a three-generation family. Further, we examined SLC1A1in probands of 98 apparently unrelated HWE families with positive histories of seizures provoked by contact with hot water. In doing so, we found three rare variants, p.Asp174Asn, p.Val251Ile and p.Ile304Met in the gene. SLC1A1 is a neuronal glutamate transporter which limits excitotoxicity and its loss-of-function leads to age-dependent neurodegeneration. We examined functional attributes of the variants in cultured mammalian cells. All three non-synonymous variants affected glutamate uptake, exhibited altered glutamate kinetics and anion conductance properties of SLC1A1. These observations provide insights into the molecular basis of hot water epilepsy and show the role of SLC1A1 variants in this intriguing neurobehavioral disorder.

  13. CYP17A1: a biochemistry, chemistry, and clinical review.

    PubMed

    Porubek, David

    2013-01-01

    Cytochrome P450 17A1 (CYP17A1; also P450c17and P450sccII) is a critically important enzyme in humans that catalyzes the formation of all endogenous androgens. It is an atypical cytochrome P450 enzyme in that it catalyzes two distinct types of substrate oxidation. Through its hydroxylase activity, it catalyzes the 17α-hydroxylation of pregnenolone to 17α-OH pregnenolone. Subsequently, through its C17,20lyase activity, it can further convert 17α-OH pregnenolone to the androgen dehydroepiandrosterone, which is a precursor to androstenedione, testosterone, and dihydrotestosterone. The importance of androgens in diseases such as prostate cancer has been appreciated for decades and the discovery of extra-testicular formation of androgens has helped clarify the pathology of the disease, especially the castrate- resistant disease. Therefore, specific inhibition of CYP17A1 by therapeutic intervention has been an area of considerable effort in several research laboratories. This basic research has led to the discovery of several promising drug candidates followed by the conduct of several clinical trials. Recently, all these efforts have culminated in the first approval by FDA of an inhibitor of CYP17A1 for the treatment of castrate-resistant prostate cancer. Ongoing clinical trials are now evaluating the agent in earlier stages of prostate cancer and even rare forms of androgen-dependent breast cancer. Accordingly, this review focuses on the biochemistry, chemistry, and clinical inhibitors of CYP17A1.

  14. Clustered O-Glycans of IgA1

    PubMed Central

    Takahashi, Kazuo; Wall, Stephanie B.; Suzuki, Hitoshi; Smith, Archer D.; Hall, Stacy; Poulsen, Knud; Kilian, Mogens; Mobley, James A.; Julian, Bruce A.; Mestecky, Jiri; Novak, Jan; Renfrow, Matthew B.

    2010-01-01

    IgA nephropathy (IgAN) is the most common primary glomerulonephritis in the world. Aberrantly glycosylated IgA1, with galactose (Gal)-deficient hinge region (HR) O-glycans, plays a pivotal role in the pathogenesis of the disease. It is not known whether the glycosylation defect occurs randomly or preferentially at specific sites. We have described the utility of activated ion-electron capture dissociation (AI-ECD) mass spectrometric analysis of IgA1 O-glycosylation. However, locating and characterizing the entire range of O-glycan attachment sites are analytically challenging due to the clustered serine and threonine residues in the HR of IgA1 heavy chain. To address this problem, we analyzed all glycoforms of the HR glycopeptides of a Gal-deficient IgA1 myeloma protein, mimicking the aberrant IgA1 in patients with IgAN, by use of a combination of IgA-specific proteases + trypsin and AI-ECD Fourier transform ion cyclotron resonance (FT-ICR) tandem mass spectrometry (MS/MS). The IgA-specific proteases provided a variety of IgA1 HR fragments that allowed unambiguous localization of all O-glycosylation sites in the six most abundant glycoforms, including the sites deficient in Gal. Additionally, this protocol was adapted for on-line liquid chromatography (LC)-AI-ECD MS/MS and LC-electron transfer dissociation MS/MS analysis. Our results thus represent a new clinically relevant approach that requires ECD/electron transfer dissociation-type fragmentation to define the molecular events leading to pathogenesis of a chronic kidney disease. Furthermore, this work offers generally applicable principles for the analysis of clustered sites of O-glycosylation. PMID:20823119

  15. ALDH3A1 — EDRN Public Portal

    Cancer.gov

    ALDH3A1 is a member of the aldehyde dehydrogenase family. They are involved in the metabolism of corticosteroids, biogenic amines, neurotransmitters, and lipid peroxidation. They are also involved in the detoxification of alcohol-derived acetaldehyde. The ALDH3A1 protein is an enzyme that forms a cytoplasmic homodimer that oxidizes aromatic and medium-chain (6 carbons or more) saturated and unsaturated aldehyde substrates. It is thought to promote resistance to UV and 4-hydroxy-2-nonenal-induced oxidative damage in the cornea. There are several splice variants that encode the same protein.

  16. Characterization of SLCO5A1/OATP5A1, a Solute Carrier Transport Protein with Non-Classical Function

    PubMed Central

    Sebastian, Katrin; Detro-Dassen, Silvia; Rinis, Natalie; Fahrenkamp, Dirk; Müller-Newen, Gerhard; Merk, Hans F.; Schmalzing, Günther

    2013-01-01

    Organic anion transporting polypeptides (OATP/SLCO) have been identified to mediate the uptake of a broad range of mainly amphipathic molecules. Human OATP5A1 was found to be expressed in the epithelium of many cancerous and non-cancerous tissues throughout the body but protein characterization and functional analysis have not yet been performed. This study focused on the biochemical characterization of OATP5A1 using Xenopus laevis oocytes and Flp-In T-REx-HeLa cells providing evidence regarding a possible OATP5A1 function. SLCO5A1 is highly expressed in mature dendritic cells compared to immature dendritic cells (∼6.5-fold) and SLCO5A1 expression correlates with the differentiation status of primary blood cells. A core- and complex- N-glycosylated polypeptide monomer of ∼105 kDa and ∼130 kDa could be localized in intracellular membranes and on the plasma membrane, respectively. Inducible expression of SLCO5A1 in HeLa cells led to an inhibitory effect of ∼20% after 96 h on cell proliferation. Gene expression profiling with these cells identified immunologically relevant genes (e.g. CCL20) and genes implicated in developmental processes (e.g. TGM2). A single nucleotide polymorphism leading to the exchange of amino acid 33 (L→F) revealed no differences regarding protein expression and function. In conclusion, we provide evidence that OATP5A1 might be a non-classical OATP family member which is involved in biological processes that require the reorganization of the cell shape, such as differentiation and migration. PMID:24376674

  17. Purification and structural characterisation of phospholipase A1 (Vespapase, Ves a 1) from Thai banded tiger wasp (Vespa affinis) venom.

    PubMed

    Sukprasert, Sophida; Rungsa, Prapenpuksiri; Uawonggul, Nunthawun; Incamnoi, Paroonkorn; Thammasirirak, Sompong; Daduang, Jureerut; Daduang, Sakda

    2013-01-01

    The Thai banded tiger wasp (Vespa affinis) is one of the most dangerous vespid species in Southeast Asia, and stinging accidents involving this species still cause fatalities. In the present study, four forms of V. affinis phospholipase A(1) were identified through a proteomics approach. Two of these enzymes were purified by reverse-phase chromatography, and their biochemical properties were characterised. These enzymes, designated Ves a 1s, are not glycoproteins and exist as 33441.5 and 33474.4 Da proteins, which corresponded with the 34-kDa band observed via SDS-PAGE. The thermal stabilities of these enzymes were stronger than snake venom. Using an in vivo assay, no difference was found in the toxicities of the different isoforms. Furthermore, the toxicity of these enzymes does not appear to be correlated with their PLA(1) activity. The cDNAs of the full-length version of Ves a 1s revealed that the Ves a 1 gene consists of a 1005-bp ORF, which encodes 334 amino acid residues, and 67- and 227-bp 5' and 3' UTRs, respectively. The two isoforms are different by three nucleotide substitutions, resulting in the replacement of two amino acids. Through sequence alignment, these enzymes were classified as members of the pancreatic lipase family. The structural modelling of Ves a 1 used the rat pancreatic lipase-related protein 2 (1bu8A) as a template because it has PLA(1) activity, which demonstrated that this enzyme belongs to the α/β hydrolase fold family. The Ves a 1 structure, which is composed of seven α-helixes and eleven β-strands, contains the β-strand/ɛSer/α-helix structural motif, which contains the Gly-X-Ser-X-Gly consensus sequence. The typical surface structures that play important roles in substrate selectivity (the lid domain and the β9 loop) were shortened in the Ves a 1 structure, which suggests that this enzyme may only exhibit phospholipase activity. Moreover, the observed insertion of proline into the lid domain of the Ves a 1 structure is rare

  18. Benzodi(pyridothiophene): a novel acceptor unit for application in A1-A-A1 type photovoltaic small molecules.

    PubMed

    Chen, Jianhua; Xiao, Manjun; Duan, Linrui; Wang, Qiong; Tan, Hua; Su, Ning; Liu, Yu; Yang, Renqiang; Zhu, Weiguo

    2016-01-21

    A series of novel A1-A-A1 type small molecules (SMs) of BDPT-2BT, BDPT-2FBT and BDPT-2DPP were designed and synthesized, in which benzodi(pyridothiophene) (BDPT) was used as a novel weak central acceptor (A) unit, and benzothiadiazole (BT), fluorinated benzothiadiazole (FBT) and diketopyrrolopyrrole (DPP) were used as terminal acceptor (A1) units, respectively. The pentacyclic BDPT aromatic unit can form big conjugated and planar SMs with the A1 unit, resulting in enhanced π-π stacking and crystallinity. The effect of the A1 unit on the optical, electrochemical and photovoltaic properties of three SMs was observed. The broader absorption spectrum, lower HOMO energy level, higher photo-response efficiency and better photovoltaic properties were exhibited for BDPT-2DPP. A maximum PCE of 3.97% with a Voc of 0.84 V, a Jsc of 9.0 mA cm(-2) and a FF of 52.37% was obtained in the BDPT-2DPP/PC71BM-based solar cells, which is 1.8 and 1.5 times the values of the BDPT-2BT and BDPT-2FBT-based cells, respectively.

  19. 26 CFR 1.669(a)-1 - Limitation on tax.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... January 1, 1969 § 1.669(a)-1 Limitation on tax. (a) In general. Section 669 provides that, at the election... received by him, from a foreign trust created by a U.S. person, on the last day of a preceding taxable year... throwback” method). This election of the beneficiary with respect to the taxable year of the beneficiary...

  20. 12 CFR 261a.1 - Authority, purpose and scope.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 261a.1 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... Governors of the Federal Reserve System (the Board) pursuant to the Privacy Act of 1974 (5 U.S.C. 552a). (b... maintenance, protection, disclosure, and amendment of records contained within systems of records maintained...

  1. 12 CFR 261a.1 - Authority, purpose and scope.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 261a.1 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... the Federal Reserve System (the Board) pursuant to the Privacy Act of 1974 (5 U.S.C. 552a). (b... maintenance, protection, disclosure, and amendment of records contained within systems of records maintained...

  2. 42 CFR 5a.1 - Statutory basis and purpose.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS RURAL PHYSICIAN TRAINING GRANT PROGRAM § 5a.1 Statutory basis and purpose. This part implements section 749B(f) of... the Rural Physician Training Grant Program. ...

  3. 42 CFR 5a.1 - Statutory basis and purpose.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Public Health PUBLIC HEALTH SERVICE, DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL PROVISIONS RURAL PHYSICIAN TRAINING GRANT PROGRAM § 5a.1 Statutory basis and purpose. This part implements section 749B(f) of... the Rural Physician Training Grant Program. ...

  4. 26 CFR 31.3306(a)-1 - Who are employers.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... TAXES AND COLLECTION OF INCOME TAX AT SOURCE EMPLOYMENT TAXES AND COLLECTION OF INCOME TAX AT SOURCE Federal Unemployment Tax Act (Chapter 23, Internal Revenue Code of 1954) § 31.3306(a)-1 Who are employers... calendar week, is with respect to such year an employer subject to the tax. (1a) For 1970 and...

  5. Passive smoking, Cyp1A1 gene polymorphism and dysmenorrhea

    PubMed Central

    Liu, Hong; Yang, Fan; Li, Zhiping; Chen, Changzhong; Fang, Zhian; Wang, Lihua; Hu, Yonghua; Chen, Dafang

    2007-01-01

    Objective This study investigated whether the association between passive smoking exposure and dysmenorrhea is modified by two susceptibility genes, CYP1A1MspI and CYP1A1HincII. Methods This report includes 1645 (1124 no dysmenorrhea, 521 dysmenorrhea) nonsmoking and nondrinking newly wed female workers at Anqing, China between June 1997 and June 2000. Multiple logistic regression models were used to estimate the associations of passive smoking exposure and genetic susceptibility with dysmenorrhea, adjusting for perceived stress. Results When stratified by women genotype, the adjusted OR of dysmenorrhea was 1.6 (95%CI=1.3-2.1) for passive smoking group with Ile/Ile462 genotype, and 1.5 (95%CI=1.1-2.1) with C/C6235 genotype, compared to non passive smoking group, respectively. The data further showed that there was a significant combined effect between passive smoking and the CYP1A1 Msp1 C/C6235 and HincII Ile/Ile462 genotype (OR=2.6, 95%CI=1.3-5.2). Conclusion CYP1A1 MspI and HincII genotypes modified the association between passive smoking and dysmenorrhea. PMID:17566695

  6. 29 CFR 1912a.1 - Purpose and scope.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Regulations Relating to Labor (Continued) OCCUPATIONAL SAFETY AND HEALTH ADMINISTRATION, DEPARTMENT OF LABOR (CONTINUED) NATIONAL ADVISORY COMMITTEE ON OCCUPATIONAL SAFETY AND HEALTH § 1912a.1 Purpose and scope. (a) Section 7(a) of the Williams-Steiger Occupational Safety and Health Act of 1970 establishes a...

  7. Milk A1 and A2 peptides and diabetes.

    PubMed

    Clemens, Roger A

    2011-01-01

    Food-derived peptides, specifically those derived from milk, may adversely affect health by increasing the risk of insulin-dependent diabetes. This position is based on the relationship of type 1 diabetes (T1D) and the consumption of variants A1 and B β-casein from cow's milk. It appears that β-casomorphin-7 (BCM-7) from β-casein may function as an immunosuppressant and impair tolerance to dietary antigens in the gut immune system, which, in turn, may contribute to the onset of T1D. There are thirteen genetic variants of β-casein in dairy cattle. Among those variants are A1, A2, and B, which are also found in human milk. The amino acid sequences of β-casomorphins among these bovine variants and those found in human milk are similar, often differing only by a single amino acid. In vitro studies indicate BCM-7 can be produced from A1 and B during typical digestive processes; however, BCM-7 is not a product of A2 digestion. Evidence from several epidemiological studies and animal models does not support the association of milk proteins, even proteins in breast milk, and the development of T1D. Ecological data, primarily based on A1/ A2 variations among livestock breeds, do not demonstrate causation, even among countries where there is considerable dairy consumption.

  8. The Heart of a 1:1 Classroom

    ERIC Educational Resources Information Center

    Tulbert, Carrie Ann

    2012-01-01

    Many educators believe that the act of building relationships is the core of learning. When technology is integrated into every classroom, do relationships improve or disintegrate among the key stakeholders in an educational environment? The purpose of this study is to determine the extent to which technology in a 1:1 school district can alter…

  9. 26 CFR 31.3402(a)-1 - Requirement of withholding.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... required to deduct and withhold the tax notwithstanding the wages are paid in something other than money (for example, wages paid in stocks or bonds; see § 31.3401 (a)-1) and to pay over the tax in money. If wages are paid in property other than money, the employer should make necessary arrangements to insure...

  10. ISS 7A.1 Flight Control Team Photo in BFCR

    NASA Image and Video Library

    2001-08-16

    JSC2001-02227 (16 August 2001) --- The members of the STS-105/ISS 7A.1 Planning team pose for a group portrait in the International Space Station (ISS) flight control room (BFCR) in Houston’s Mission Control Center (MCC).

  11. THE EFFECTIVENESS OF A-1 BOMBING ATTACKS ON BRIDGES

    DTIC Science & Technology

    This study determines the effectiveness of various A -1 aircraft payloads against bridges. The optimum load, regardless of bridge type, consists of...eight-500 lb bombs plus additional ordnance as permitted by radius , loading time, and weight considerations. The effects of different intervalometer

  12. COX7A1 — EDRN Public Portal

    Cancer.gov

    COX7A1, cytochrome c oxidase subunit VIIa polypeptide 1 (muscle), is one of the polypeptide chains of cytochrome c oxidase, the terminal component of the mitochondrial respiratory chain. This polypeptide is present only in muscle tissues. Other polypeptides of subunit VIIa are present in both muscle and nonmuscle tissues, and are encoded by different genes.

  13. Regulation of Human Cytochrome P4501A1 (hCYP1A1): A Plausible Target for Chemoprevention?

    PubMed Central

    Santes-Palacios, Rebeca; Ornelas-Ayala, Diego; Cabañas, Noel; Marroquín-Pérez, Ana; Hernández-Magaña, Alexis; del Rosario Olguín-Reyes, Sitlali

    2016-01-01

    Human cytochrome P450 1A1 (hCYP1A1) has been an object of study due to its role in precarcinogen metabolism; for this reason it is relevant to know more in depth the mechanisms that rule out its expression and activity, which make this enzyme a target for the development of novel chemiopreventive agents. The aim of this work is to review the origin, regulation, and structural and functional characteristics of CYP1A1 letting us understand its role in the bioactivation of precarcinogen and the consequences of its modulation in other physiological processes, as well as guide us in the study of this important protein. PMID:28105425

  14. Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus.

    PubMed

    McGrath, H

    2017-10-01

    Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is "autoimmunity." Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of these

  15. Ultraviolet-A1 irradiation therapy for systemic lupus erythematosus

    PubMed Central

    2017-01-01

    Systemic lupus erythematosus (lupus, SLE) is a chronic autoimmune disease characterized by the production of autoantibodies, which bind to antigens and are deposited within tissues to fix complement, resulting in widespread systemic inflammation. The studies presented herein are consistent with hyperpolarized, adenosine triphosphate (ATP)-deficient mitochondria being central to the disease process. These hyperpolarized mitochondria resist the depolarization required for activation-induced apoptosis. The mitochondrial ATP deficits add to this resistance to apoptosis and also reduce the macrophage energy that is needed to clear apoptotic bodies. In both cases, necrosis, the alternative pathway of cell death, results. Intracellular constituents spill into the blood and tissues, eliciting inflammatory responses directed at their removal. What results is “autoimmunity.” Ultraviolet (UV)-A1 photons have the capacity to remediate this aberrancy. Exogenous exposure to low-dose, full-body, UV-A1 radiation generates singlet oxygen. Singlet oxygen has two major palliative actions in patients with lupus and the UV-A1 photons themselves have several more. Singlet oxygen depolarizes the hyperpolarized mitochondrion, triggering non-ATP-dependent apoptosis that deters necrosis. Next, singlet oxygen activates the gene encoding heme oxygenase (HO-1), a major governor of systemic homeostasis. HO-1 catalyzes the degradation of the oxidant heme into biliverdin (converted to bilirubin), Fe, and carbon monoxide (CO), the first three of these exerting powerful antioxidant effects, and in conjunction with a fourth, CO, protecting against injury to the coronary arteries, the central nervous system, and the lungs. The UV-A1 photons themselves directly attenuate disease in lupus by reducing B cell activity, preventing the suppression of cell-mediated immunity, slowing an epigenetic progression toward SLE, and ameliorating discoid and subacute cutaneous lupus. Finally, a combination of

  16. Characterization of UDP-glucuronosyltransferase 2A1 (UGT2A1) variants and their potential role in tobacco carcinogenesis

    PubMed Central

    Bushey, Ryan T.; Chen, Gang; Blevins-Primeau, Andrea S.; Krzeminski, Jacek; Amin, Shantu; Lazarus, Philip

    2010-01-01

    UDP-glucuronosyltransferases (UGTs) play an important role in the metabolism and excretion of various endogenous and xenobiotic compounds, including carcinogens and chemotherapeutic agents. The goal of the present study was to examine UGT2A1 expression in human tissues, determine its glucuronidation activity against tobacco carcinogens, and assess the potential functional role of UGT2A1 missense single nucleotide polymorphisms on UGT2A1 enzyme activity. As determined by reverse-transcription polymerase chain reaction, UGT2A1 was expressed in aerodigestive tract tissues including trachea, larynx and tonsil, and was also expressed in lung and colon; no expression was observed in breast, whole brain, pancreas, prostate, kidney, liver or esophagus. Real-time PCR suggested that UGT2A1 exhibited highest expression in the lung, followed by trachea > tonsil > larynx > colon > olfactory tissue. Cell homogenates prepared from wild-type UGT2A175Lys308Gly-over-expressing HEK293 cells showed significant glucuronidation activity, as observed by reverse-phase UPLC, against a variety of polycyclic aromatic hydrocarbons (PAHs) including, 1-hydroxy-benzo(a)pyrene, benzo(a)pyrene-7,8-diol, and 5-methylchrysene-1,2-diol. No activity was observed in UGT2A1-over-expressing cell homogenate against substrates that form N-glucuronides, such as NNAL, nicotine, or N-OH-PhIP. A significant (p<0.05) ~25% decrease in glucuronidation activity (Vmax/KM) was observed against all PAH substrates for the UGT2A175Arg308Gly variant as compared to homogenates from wild-type UGT2A175Lys308Gly; no activity was observed for cell homogenates over-expressing the UGT2A175Lys308Arg variant for all substrates tested. These data suggest that UGT2A1 is an important detoxification enzyme in the metabolism of PAHs within target tissues for tobacco carcinogens, and functional polymorphisms in UGT2A1 may play a role in tobacco-related cancer risk. PMID:21164388

  17. a1(1420 ) peak as the π f0(980 ) decay mode of the a1(1260 )

    NASA Astrophysics Data System (ADS)

    Aceti, F.; Dai, L. R.; Oset, E.

    2016-11-01

    We study the decay mode of the a1(1260 ) into a π+ in p wave and the f0(980 ) that decays into π+π- in s wave. The mechanism proceeds via a triangular mechanism where the a1(1260 ) decays into K*K ¯, the K* decays to an external π+ and an internal K that fuses with the K ¯ producing the f0(980 ) resonance. The mechanism develops a singularity at a mass of the a1(1260 ) around 1420 MeV, producing a peak in the cross section of the π p reaction, used to generate the mesonic final state, which provides a natural explanation of all the features observed in the COMPASS experiment, where a peak observed at this energy is tentatively associated to a new resonance called a1(1420 ). On the other hand, the triangular singularity studied here gives rise to a remarkable feature, where a peak is seen for a certain decay channel of a resonance at an energy about 200 MeV higher than its nominal mass.

  18. Evaluation of LLTR Series II tests A-1A and A-1B test results. [Large Leak Test Rig

    SciTech Connect

    Shoopak, B F; Amos, J C; Norvell, T J

    1980-03-01

    The standard methodology, with minor modifications provides conservative yet realistic predictions of leaksite and other sodium system pressures in the LLTR Series II vessel and piping. The good agreement between predicted and measured pressures indicates that the TRANSWRAP/RELAP modeling developed from the Series I tests is applicable to larger scale units prototypical of the Clinch River steam generator design. Calculated sodium system pressures are sensitive to several modeling parameters including rupture disc modeling, acoustic velocity in the test vessel, and flow rate from the rupture tube. The acoustic velocity which produced best agreement with leaksite pressures was calculated based on the shroud diameter and shroud wall thickness. The corresponding rupture tube discharge coefficient was that of the standard design methodology developed from Series I testing. As found in Series I testing, the Series II data suggests that the leading edge of the flow in the relief line is two phase for a single, doubled-ended guillotine tube rupture. The steam generator shroud acts as if it is relatively transparent to the transmission of radial pressures to the vessel wall. Slightly lower sodium system maximum pressures measured during Test A-1b compared to Test A-1a are attributed to premature failure (failure at a lower pressure) of the rupture disc in contact with the sodium for test A-1b. The delay in failure of the second disc in Test A-1b, which was successfully modeled with TRANSWRAP, is attributed to the limited energy in the nitrogen injection.

  19. Bafilomycin A1 and intracellular multiplication of Legionella pneumophila.

    PubMed Central

    Cattani, L; Goldoni, P; Pastoris, M C; Sinibaldi, L; Orsi, N

    1997-01-01

    Multiplication of Legionella pneumophila in HeLa cells was found to be inhibited by noncytotoxic concentrations of bafilomycin A1, with blockage of bacterial growth at a concentration 15.6 nM. The inhibiting action was evident only when the antibiotic was present during the initial phase of intracellular multiplication, i.e., during the formation of the phagosome, whereas the addition of the drug did not affect microorganisms already actively multiplying within the phagosome. PMID:8980784

  20. SPICE macromodel for a 1-megawatt power MOSFET switch

    SciTech Connect

    Helms, C.; Ackermann, M.; Fischer, T.; Deveney, M.

    1993-08-01

    This paper presents a SPICE macromodel for a 1-megawatt high power electrical switch which uses power MOSFETs as the active switching elements. The model accurately predicts the time dependent switching current and provides a reasonable representation of the time dependent switch resistance and voltage drop across the switch. Techniques for extracting model parameters for commercial power MOSFETs are discussed along with suggestions for extending the model to spark gaps and other high power switches.

  1. C/2013 A1 (Siding Spring vs. Mars)

    NASA Technical Reports Server (NTRS)

    Moorhead, Althea; Cooke, William

    2013-01-01

    Comet C/2013 A1 (Siding Spring): recently discovered long period comet. Will have close encounter with Mars on October 19, 2014. Collision is extremely unlikely. Passing through the coma and/or tail is likely. Increases risk to Martian spacecraft. Meteoroids (100 microns or larger): approx. or <20% chance of impact per square meter due to coma and tail. Gas may also a ect Martian atmosphere.

  2. ISS 7A.1 Flight Control Team Photo in BFCR

    NASA Image and Video Library

    2001-08-16

    JSC2001-02229 (16 August 2001) --- The members of the STS-105/ISS 7A.1 Orbit 1 team pose for a group portrait in the International Space Station (ISS) flight control room (BFCR) in Houston’s Mission Control Center (MCC). Flight director Mark Ferring is kneeling as he holds the Expedition Three mission logo. Astronaut Stephanie D. Wilson, ISS spacecraft communicator (CAPCOM), is standing behind Ferring.

  3. Phylogenetic diversity of Pasteurellaceae and horizontal gene transfer of leukotoxin in wild and domestic sheep.

    PubMed

    Kelley, Scott T; Cassirer, E Frances; Weiser, Glen C; Safaee, Shirin

    2007-01-01

    Wild and domestic animal populations are known to be sources and reservoirs of emerging diseases. There is also a growing recognition that horizontal genetic transfer (HGT) plays an important role in bacterial pathogenesis. We used molecular phylogenetic methods to assess diversity and cross-transmission rates of Pasteurellaceae bacteria in populations of bighorn sheep, Dall's sheep, domestic sheep and domestic goats. Members of the Pasteurellaceae cause an array of deadly illnesses including bacterial pneumonia known as "pasteurellosis", a particularly devastating disease for bighorn sheep. A phylogenetic analysis of a combined dataset of two RNA genes (16S ribosomal RNA and RNAse P RNA) revealed remarkable evolutionary diversity among Pasteurella trehalosi and Mannheimia (Pasteurella) haemolytica bacteria isolated from sheep and goats. Several phylotypes appeared to associate with particular host species, though we found numerous instances of apparent cross-transmission among species and populations. Statistical analyses revealed that host species, geographic locale and biovariant classification, but not virulence, correlated strongly with Pasteurellaceae phylogeny. Sheep host species correlated with P. trehalosi isolates phylogeny (PTP test; P=0.002), but not with the phylogeny of M. haemolytica isolates, suggesting that P. trehalosi bacteria may be more host specific. With regards to populations within species, we also discovered a strong correlation between geographic locale and isolate phylogeny in the Rocky Mountain bighorn sheep (PTP test; P=0.001). We also investigated the potential for HGT of the leukotoxin A (lktA) gene, which produces a toxin that plays an integral role in causing disease. Comparative analysis of the combined RNA gene phylogeny and the lktA phylogenies revealed considerable incongruence between the phylogenies, suggestive of HGT. Furthermore, we found identical lktA alleles in unrelated bacterial species, some of which had been isolated

  4. Catechol-O-methyltransferase association with hemoglobin A1c

    PubMed Central

    Hall, Kathryn T.; Jablonski, Kathleen A.; Chen, Ling; Harden, Maegan; Tolkin, Benjamin R.; Kaptchuk, Ted J.; Bray, George A.; Ridker, Paul M.; Florez, Jose C.; Chasman, Daniel I.

    2016-01-01

    Aims Catecholamines have metabolic effects on blood pressure, insulin sensitivity and blood glucose. Genetic variation in catechol-O-methyltransferase (COMT), an enzyme that degrades catecholamines, is associated with cardiometabolic risk factors and incident cardiovascular disease (CVD). Here we examined COMT effects on glycemic function and type 2 diabetes. Methods We tested whether COMT polymorphisms were associated with baseline HbA1c in the Women’s Genome Health Study (WGHS), and Meta-Analyses of Glucose and Insulin-related traits Consortium (MAGIC), and with susceptibility to type 2 diabetes in WGHS, DIAbetes Genetics Replication And Meta-analysis consortium (DIAGRAM), and the Diabetes Prevention Program (DPP). Given evidence that COMT modifies some drug responses, we examined association with type 2 diabetes and randomized metformin and aspirin treatment. Results COMT rs4680 high-activity G-allele was associated with lower HbA1c in WGHS (β = −0.032% [0.012], p = 0.008) and borderline significant in MAGIC (β = −0.006% [0.003], p = 0.07). Combined COMT per val allele effects on type 2 diabetes were significant (OR = 0.98 [0.96–0.998], p = 0.03) in fixed-effects analyses across WGHS, DIAGRAM, and DPP. Similar results were obtained for 2 other COMT SNPs rs4818 and rs4633. In the DPP, the rs4680 val allele was borderline associated with lower diabetes incidence among participants randomized to metformin (HR = 0.81 [0.65–1.00], p = 0.05). Conclusions COMT rs4680 high-activity G-allele was associated with lower HbA1c and modest protection from type 2 diabetes. The directionality of COMT associations was concordant with those previously observed for cardiometabolic risk factors and CVD. PMID:27282867

  5. Sulfotransferase 1A1 Substrate Selectivity: A Molecular Clamp Mechanism.

    PubMed

    Cook, Ian; Wang, Ting; Leyh, Thomas S

    2015-10-06

    The human cytosolic sulfotransferases (SULTs) regulate hundreds, perhaps thousands, of small molecule metabolites and xenobiotics via transfer of a sulfuryl moiety (-SO3) from PAPS (3'-phosphoadenosine 5'-phosphosulfate) to the hydroxyls and primary amines of the recipients. In liver, where it is abundant, SULT1A1 engages in modifying metabolites and neutralizing toxins. The specificity of 1A1 is the broadest of any SULT, and understanding its selectivity is fundamental to understanding its biology. Here, for the first time, we show that SULT1A1 substrates separate naturally into two classes: those whose affinities are either enhanced ∼20-fold (positive synergy) or unaffected (neutral synergy) by the presence of a saturating nucleotide. kcat for the positive-synergy substrates is shown to be ∼100-fold greater than that of neutral-synergy compounds; consequently, the catalytic efficiency (kcat/Km) is approximately 3 orders of magnitude greater for the positive-synergy species. All-atom dynamics modeling suggests a molecular mechanism for these observations in which the binding of only positive-synergy compounds causes two phenylalanine residues (F81 and 84) to reposition and "sandwich" the phenolic moiety of the substrates, thus enhancing substrate affinity and positioning the nucleophilic oxygen for attack. Molecular dynamics movies reveal that the neutral-synergy compounds "wander" about the active site, infrequently achieving a reactive position. In-depth analysis of select point mutants strongly supports the model and provides an intimate view of the interdependent catalytic functions of subsections of the active site.

  6. Nanofluidic sustainable energy conversion using a 1D nanofluidic network.

    PubMed

    Kim, Sang Hui; Kwak, Seungmin; Han, Sung Il; Chun, Dong Won; Lee, Kyu Hyoung; Kim, Jinseok; Lee, Jeong Hoon

    2014-05-01

    We propose a 1-dimensional (1D) nanofluidic energy conversion device by implementing a surface-patterned Nafion membrane for the direct energy conversion of the pressure to electrical power. By implementing a -200-nm-thick nano-bridge with a 5-nm pore size between two microfluidic channels, we acquired an effective streaming potential of 307 mV and output power of 94 pW with 0.1 mM KCI under pressure difference of 45 MPa. The experimental results show both the effects of applied pressure differences and buffer concentrations on the effective streaming potential, and are consistent with the analytical prediction.

  7. Elbow joint luxation in a 1-month-old foal.

    PubMed

    Rubio-Martínez, L M; Vázquez, F J; Romero, A; Ormazábal, J R

    2008-01-01

    This paper reports on luxation of the elbow joint without concomitant fracture in a 1-month-old foal. Conservative treatment, with closed reduction and full-limb bandaging, including caudal and lateral splints, seemed successful initially, however, failed to provide enough stability and luxation recurred, and open reduction and surgical placement of prosthetic collateral ligaments was required. Luxation of the elbow joint should be considered when acute non-weight bearing forelimb lameness occurs associated with pain and swelling in the area of the elbow in young foals. Closed reduction failed to provide sufficient joint stability.

  8. A 1:1 apochromat transfer lens system

    NASA Technical Reports Server (NTRS)

    Tifft, W. G.; Buchroeder, R. A.

    1971-01-01

    A prototype system for remote control was constructed for the University of Arizona 90-inch telescope on Kitt Peak. The system uses image dissector tubes, a conventional photocell, and photographic plates as detectors for images formed at the Cassegrain focus of the 90-inch telescope. It was decided to use an image relay system to transfer selected portions of the image plane to image dissectors and the photographic plate. The design of a 1:1 relay system is described. Design considerations are discussed and alternate designs are outlined.

  9. Stimulation of ectodermal organ development by Ectodysplasin-A1.

    PubMed

    Mustonen, Tuija; Pispa, Johanna; Mikkola, Marja L; Pummila, Marja; Kangas, Aapo T; Pakkasjärvi, Leila; Jaatinen, Risto; Thesleff, Irma

    2003-07-01

    Organs developing as ectodermal appendages share similar early morphogenesis and molecular mechanisms. Ectodysplasin, a signaling molecule belonging to the tumor necrosis factor family, and its receptor Edar are required for normal development of several ectodermal organs in humans and mice. We have overexpressed two splice forms of ectodysplasin, Eda-A1 and Eda-A2, binding to Edar and another TNF receptor, Xedar, respectively, under the keratin 14 (K14) promoter in the ectoderm of transgenic mice. Eda-A2 overexpression did not cause a detectable phenotype. On the contrary, overexpression of Eda-A1 resulted in alterations in a variety of ectodermal organs, most notably in extra organs. Hair development was initiated continuously from E14 until birth, and in addition, the transgenic mice had supernumerary teeth and mammary glands, phenotypes not reported previously in transgenic mice. Also, hair composition and structure was abnormal, and the cycling of hairs was altered so that the growth phase (anagen) was prolonged. Both hairs and nails grew longer than normal. Molar teeth were of abnormal shape, and enamel formation was severely disturbed in incisors. Furthermore, sweat gland function was stimulated and sebaceous glands were enlarged. We conclude that ectodysplasin-Edar signaling has several roles in ectodermal organ development controlling their initiation, as well as morphogenesis and differentiation.

  10. The S1( 1A1)- S0( 1A1) Electronic Transition of Jet-Cooled o-Difluorobenzene

    NASA Astrophysics Data System (ADS)

    Swinn, Anna K.; Kable, Scott H.

    1998-09-01

    A detailed study of theS1(1A1)-S0(1A1) transition of jet-cooledo-difluorobenzene has been completed using the two techniques of laser-induced fluorescence excitation and dispersed, single vibronic level fluorescence spectroscopy. Analysis of over 60 dispersed fluorescence spectra resulted in both the assignment of 22 excited state vibrational frequencies and the confirmation of 23 ground state frequencies. The spectrum is dominated by Franck-Condon activity in totally symmetric vibrations with long progressions in the ring-breathing mode, ν9. By analogy with benzene and thepara- andmeta-substituted isomers, two vibronic coupling mechanisms are postulated to be responsible for the wealth of weaker symmetry-forbidden structure that has been observed. Single quantum changes inb2vibrations are postulated to appear due to first order vibronic coupling to a higher lyingB2electronic state. Combinations ofb1anda2modes are postulated to appear from second order vibronic coupling to anA1electronic state. This second order coupling causes a pronounced Duschinsky mixing among excited stateb1anda2modes with respect to their ground state counterparts. Franck-Condon factors are calculated for thea1progression-forming modes, anharmonic contributions are evaluated, one strong Fermi resonance is identified and analyzed, and the Duschinsky rotation matrix elements are evaluated for the most strongly affected modes, ν17and ν18. Several transitions in theoDFB-oDFB van der Waals dimer andoDFB-Ar complex are also assigned in the spectrum.

  11. Collisionally-Mediated Singlet-Triplet Crossing in ˜{a}1A1 CH_2 Revisited: (010) Coupling

    NASA Astrophysics Data System (ADS)

    Le, Anh T.; Hall, Gregory; Sears, Trevor

    2014-06-01

    Methylene, CH2, possesses a ground ˜{X}3B1 ground electronic state and an excited ˜{a}1A1 state only 3150cm-1 higher in energy. The collision-induced singlet-triplet crossing in the gaseous mixtures is important in determining overall reaction rates and chemical behavior. Accidental near-degeneracies between rotational levels of the singlet state and the vibrationally excited triplet state result in a few gateway rotational levels that mediate collision-induced intersystem crossing. The mixed states can be recognized and quantified by deperturbation, knowing the zero-order singlet and triplet energy levels. Hyperfine structure can be used as alternative indicator of singlet-triplet mixing. Non-zero mixing will induce hyperfine splittings intermediate between the unresolved hyperfine structure of pure singlet and the resolvable (≈50MHz) splittings of pure triplet, arising from the (I\\cdotS) interaction in the ortho states, where nuclear spin I=1. Collision-induced intersystem crossing rates from the (010) state are comparable to those for (000), yet the identities and characters of the presumed gateway states are unknown. A new spectrometer is under construction to investigate triplet mixing rotational levels of ˜{a}1A1(010) by sub-Doppler measurements of perturbation-induced hyperfine splittings. Their observation will permit the identification of gateway states and quantification of the degree of triplet contamination of the singlet wavefunction. Progress in the measurements and the analysis of rotational energy transfer in (010) will be reported. Acknowledgments: Work at Brookhaven National Laboratory was carried out under Contract No. DE-AC02-98CH10886 with the U.S. Department of Energy and supported by its Office of Basic Energy Sciences, Division of Chemical Sciences, Geosciences and Biosciences. C.-H. Chang, G. E. Hall, T. J. Sears, J. Chem. Phys 133, 144310(2010) G. E. Hall, A. V. Komissarov, and T. J. Sears, J. Phys. Chem. A 108 7922-7927 (2004)

  12. [Microsurgical anatomy importance of A1-anterior communicating artery complex].

    PubMed

    Monroy-Sosa, Alejandro; Pérez-Cruz, Julio César; Reyes-Soto, Gervith; Delgado-Hernández, Carlos; Macías-Duvignau, Mario Alberto; Delgado-Reyes, Luis

    2013-01-01

    Antecedentes: la arteria cerebral anterior se origina de la bifurcación de la arteria carótida interna lateral al quiasma óptico, posteriormente se une con su homóloga contralateral mediante la arteria comunicante anterior. El complejo precomunicante(A1)-arteria comunicante anterior es el lugar más frecuente de variantes anatómicas y el sitio con mayor cantidad de aneurismas (30 a 37%). Objetivo: conocer la anatomía microquirúrgica, las variantes anatómicas y la importancia del complejo segmento precomunicante-arteria comunicante anterior en cirugía neurológica de la patología vascular, principalmente aneurismas, en población mexicana. Material y métodos: estudio prospectivo y descriptivo efectuado en el Departamento de Anatomía de la Facultad de Medicina (UNAM) en 30 encéfalos inyectados. Se estudió la anatomía microquirúrgica (longitud y calibre) del complejo segmento precomunicante-arteria comunicante anterior de la arteria cerebral anterior y sus variantes. Resultados: se encontraron 60 segmentos precomunicantes. La longitud promedio del lado izquierdo fue de 11.35 mm y del derecho de 11.84 mm. El calibre medio en el lado izquierdo fue de 1.67 mm y en el derecho de 1.64 mm. El número promedio de perforantes en el lado izquierdo fue de 7.9 y en el derecho de 7.5. La arteria comunicante anterior se encontró en 29 encéfalos sobre el quiasma óptico, su trayecto dependió de la longitud del segmento A1. La longitud media del segmento fue de 2.84 mm, el calibre fue de 1.41 mm y el número promedio de perforantes de 3.27. En 18 encéfalos (60%) se encontraron variantes del complejo A1-arteria comunicante anterior y dos aneurismas tipo blíster. Conclusión: es necesario entender la anatomía microquirúrgica del complejo segmento precomunicante-arteria comunicante anterior y conocer las variantes para tener una visión en tercera dimensión durante la cirugía de aneurismas.

  13. Stress significantly increases mortality following a secondary bacterial respiratory infection

    PubMed Central

    2012-01-01

    A variety of mechanisms contribute to the viral-bacterial synergy which results in fatal secondary bacterial respiratory infections. Epidemiological investigations have implicated physical and psychological stressors as factors contributing to the incidence and severity of respiratory infections and psychological stress alters host responses to experimental viral respiratory infections. The effect of stress on secondary bacterial respiratory infections has not, however, been investigated. A natural model of secondary bacterial respiratory infection in naive calves was used to determine if weaning and maternal separation (WMS) significantly altered mortality when compared to calves pre-adapted (PA) to this psychological stressor. Following weaning, calves were challenged with Mannheimia haemolytica four days after a primary bovine herpesvirus-1 (BHV-1) respiratory infection. Mortality doubled in WMS calves when compared to calves pre-adapted to weaning for two weeks prior to the viral respiratory infection. Similar results were observed in two independent experiments and fatal viral-bacterial synergy did not extend beyond the time of viral shedding. Virus shedding did not differ significantly between treatment groups but innate immune responses during viral infection, including IFN-γ secretion, the acute-phase inflammatory response, CD14 expression, and LPS-induced TNFα production, were significantly greater in WMS versus PA calves. These observations demonstrate that weaning and maternal separation at the time of a primary BHV-1 respiratory infection increased innate immune responses that correlated significantly with mortality following a secondary bacterial respiratory infection. PMID:22435642

  14. X-ray crystallographic structure of a bacterial polysialyltransferase provides insight into the biosynthesis of capsular polysialic acid.

    PubMed

    Lizak, Christian; Worrall, Liam J; Baumann, Lars; Pfleiderer, Moritz M; Volkers, Gesa; Sun, Tianjun; Sim, Lyann; Wakarchuk, Warren; Withers, Stephen G; Strynadka, Natalie C J

    2017-07-19

    Polysialic acid (polySia) is a homopolymeric saccharide that is associated with some neuroinvasive pathogens and is found on selective cell types in their eukaryotic host. The presence of a polySia capsule on these bacterial pathogens helps with resistance to phagocytosis, cationic microbial peptides and bactericidal antibody production. The biosynthesis of bacterial polySia is catalysed by a single polysialyltransferase (PST) transferring sialic acid from a nucleotide-activated donor to a lipid-linked acceptor oligosaccharide. Here we present the X-ray structure of the bacterial PST from Mannheimia haemolytica serotype A2, thereby defining the architecture of this class of enzymes representing the GT38 family. The structure reveals a prominent electropositive groove between the two Rossmann-like domains forming the GT-B fold that is suitable for binding of polySia chain products. Complex structures of PST with a sugar donor analogue and an acceptor mimetic combined with kinetic studies of PST active site mutants provide insight into the principles of substrate binding and catalysis. Our results are the basis for a molecular understanding of polySia biosynthesis in bacteria and might assist the production of polysialylated therapeutic reagents and the development of novel antibiotics.

  15. Biofilm bacteria: formation and comparative susceptibility to antibiotics

    PubMed Central

    Olson, Merle E.; Ceri, Howard; Morck, Douglas W.; Buret, Andre G.; Read, Ronald R.

    2002-01-01

    The Calgary Biofilm Device (CBD) was used to form bacterial biofilms of selected veterinary gram-negative and gram-positive pathogenic bacteria from cattle, sheep, pigs, chicken, and turkeys. The minimum inhibitory concentration (MIC) and minimum biofilm eradication concentration (MBEC) of ampicillin, ceftiofur, cloxacillin, oxytetracycline, penicillin G, streptomycin, tetracycline, enrofloxacin, erythromycin, gentamicin, tilmicosin, and trimethoprim-sulfadoxine for gram-positive and -negative bacteria were determined. Bacterial biofilms were readily formed on the CBD under selected conditions. The biofilms consisted of microcolonies encased in extracellular polysaccharide material. Biofilms composed of Arcanobacterium (Actinomyces) pyogenes, Staphylococcus aureus, Staphylococcus hyicus, Streptococcus agalactiae, Corynebacterium renale, or Corynebacterium pseudotuberculosis were not killed by the antibiotics tested but as planktonic bacteria they were sensitive at low concentrations. Biofilm and planktonic Streptococcus dysgalactiae and Streptococcus suis were sensitive to penicillin, ceftiofur, cloxacillin, ampicillin, and oxytetracycline. Planktonic Escherichia coli were sensitive to enrofloxacin, gentamicin, oxytetracycline and trimethoprim/ sulfadoxine. Enrofloxacin and gentamicin were the most effective antibiotics against E. coli growing as a biofilm. Salmonella spp. and Pseudomonas aeruginosa isolates growing as planktonic populations were sensitive to enrofloxacin, gentamicin, ampicillin, oxytetracycline, and trimethoprim/sulfadoxine, but as a biofilm, these bacteria were only sensitive to enrofloxacin. Planktonic and biofilm Pasteurella multocida and Mannheimia haemolytica had similar antibiotic sensitivity profiles and were sensitive to most of the antibiotics tested. The CBD provides a valuable new technology that can be used to select antibiotics that are able to kill bacteria growing as biofilms. PMID:11989739

  16. The importance of interleukin-8 as a neutrophil chemoattractant in the lungs of cattle with pneumonic pasteurellosis.

    PubMed Central

    Caswell, J L; Middleton, D M; Gordon, J R

    2001-01-01

    Interleukin-8 (IL-8), an in vitro and in vivo neutrophil chemoattractant, is expressed at high levels in the lesions observed in bovine pneumonic pasteurellosis. Because of the role of neutrophils in the pathogenesis of pneumonic pasteurellosis, we investigated the relative importance of IL-8 as a neutrophil chemoattractant in this disease. Bronchoalveolar lavage (BAL) fluid was harvested from calves experimentally infected with bovine herpesvirus-1 and challenged with Mannheimia haemolytica. Neutrophil chemotactic activity was measured in pneumonic BAL fluid samples treated with a neutralizing monoclonal antibody to ovine IL-8, and compared to the activity in samples treated with an isotype-matched control antibody. Bronchoalveolar lavage fluid was analyzed at a dilution which induced a half-maximal response, and the concentrations of antibody were optimized in a preliminary experiment. Following incubation of replicate samples of diluted pneumonic bovine BAL fluid with 70 microg/mL of IL-8-neutralizing antibody or control antibody, the neutrophil chemotactic activities of the samples were determined using an in vitro microchemotaxis assay. Overall, pretreatment of BAL fluid samples with neutralizing anti-IL-8 antibody reduced neutrophil chemotactic activity by 15% to 60%, compared to pretreatment with control antibody. This effect was highly significant (P < 0.001), and was present in 5 of 5 samples. These data indicate that IL-8 is an important neutrophil chemoattractant in calves with pneumonic pasteurellosis, but that mediators with actions redundant to those of IL-8 must also be present in the lesions. PMID:11768129

  17. Diseases and pathogens associated with mortality in Ontario beef feedlots.

    PubMed

    Gagea, Mihai I; Bateman, Kenneth G; van Dreumel, Tony; McEwen, Beverly J; Carman, Susy; Archambault, Marie; Shanahan, Rachel A; Caswell, Jeff L

    2006-01-01

    This study determined the prevalence of diseases and pathogens associated with mortality or severe morbidity in 72 Ontario beef feedlots in calves that died or were euthanized within 60 days after arrival. Routine pathologic and microbiologic investigations, as well as immunohistochemical staining for detection of bovine viral diarrhea virus (BVDV) antigen, were performed on 99 calves that died or were euthanized within 60 days after arrival. Major disease conditions identified included fibrinosuppurative bronchopneumonia (49%), caseonecrotic bronchopneumonia or arthritis (or both) caused by Mycoplasma bovis (36%), viral respiratory disease (19%), BVDV-related diseases (21%), Histophilus somni myocarditis (8%), ruminal bloat (2%), and miscellaneous diseases (8%). Viral infections identified were BVDV (35%), bovine respiratory syncytial virus (9%), bovine herpesvirus-1 (6%), parainfluenza-3 virus (3%), and bovine coronavirus (2%). Bacteria isolated from the lungs included M. bovis (82%), Mycoplasma arginini (72%), Ureaplasma diversum (25%), Mannheimia haemolytica (27%), Pasteurella multocida (19%), H. somni (14%), and Arcanobacterium pyogenes (19%). Pneumonia was the most frequent cause of mortality of beef calves during the first 2 months after arrival in feedlots, representing 69% of total deaths. The prevalence of caseonecrotic bronchopneumonia caused by M. bovis was similar to that of fibrinosuppurative bronchopneumonia, and together, these diseases were the most common causes of pneumonia and death. M. bovis pneumonia and polyarthritis has emerged as an important cause of mortality in Ontario beef feedlots.

  18. The OmpA family of proteins: roles in bacterial pathogenesis and immunity.

    PubMed

    Confer, Anthony W; Ayalew, Sahlu

    2013-05-03

    The OmpA family of outer membrane proteins is a group of genetically related, heat-modifiable, surface-exposed, porin proteins that are in high-copy number in the outer membrane of mainly Gram-negative bacteria. OmpA proteins are characterized by an N-terminal domain that forms an eight-stranded, anti-parallel β barrel, which is embedded in the outer membrane. The C-terminal domain is globular and located in the periplasmic space. Escherichia coli OmpA is the best characterized of the proteins. Other well-characterized OmpA-equivalent proteins from pathogenic bacteria include Pseudomonas aeruginosa OprF, Haemophilus influenzae P5, Klebsiella pneumoniae OmpA, and Chlamydia trachomatis major outer membrane protein (MOMP). OmpA from the veterinary pathogens Mannheimia haemolytica, Haemophilus parasuis, Leptospira interrogans, and Pasteurella multocida have been studied to a lesser extent. Among many of the pathogenic bacteria, OmpA proteins have important pathogenic roles including bacterial adhesion, invasion, or intracellular survival as well as evasion of host defenses or stimulators of pro-inflammatory cytokine production. These pathogenic roles are most commonly associated with central nervous system, respiratory and urogenital diseases. Alternatively, OmpA family proteins can serve as targets of the immune system with immunogenicity related to surface-exposed loops of the molecule. In several cases, OmpA proteins are under evaluation as potential vaccine candidates.

  19. Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex.

    PubMed

    Kishimoto, Mai; Tsuchiaka, Shinobu; Rahpaya, Sayed Samim; Hasebe, Ayako; Otsu, Keiko; Sugimura, Satoshi; Kobayashi, Suguru; Komatsu, Natsumi; Nagai, Makoto; Omatsu, Tsutomu; Naoi, Yuki; Sano, Kaori; Okazaki-Terashima, Sachiko; Oba, Mami; Katayama, Yukie; Sato, Reiichiro; Asai, Tetsuo; Mizutani, Tetsuya

    2017-03-18

    Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets.

  20. Vaccination schedules in small ruminant farms.

    PubMed

    Lacasta, D; Ferrer, L M; Ramos, J J; González, J M; Ortín, A; Fthenakis, G C

    2015-12-14

    Development and implementation of health management plans is the cornerstone of profitable farms; prevention of microbial diseases by means of vaccination is an integral part of such a plan. In every production type and management system in small ruminants, microbial diseases have a major significance, hence their proper control must be based in good health management practices, including use of effective and safe vaccines. Development of various types of vaccines is evolving very quickly in recent years and the improvement of new type of vaccines offers prospects. The article reviews and discusses vaccination programs and latest advances in development of vaccines against diseases that cause major economic losses in small ruminants. Specifically, vaccination schedules for the following diseases are reviewed: bacterial abortion (abortion associated with Brucella melitensis, Campylobacter spp., Chlamydophila abortus, Coxiella burnetii, Salmonella abortus ovis or Salmonella brandenburg), caseous lymphadenitis, clostridial diseases, colibacillosis, contagious echtyma, epididymitis caused by Brucella ovis, footrot, mammary diseases (contagious agalactia, mastitis), paratuberculosis and respiratory diseases (respiratory disease caused by Mannheimia haemolytica or other Pasteurellaceae).

  1. Tulathromycin Exerts Proresolving Effects in Bovine Neutrophils by Inhibiting Phospholipases and Altering Leukotriene B4, Prostaglandin E2, and Lipoxin A4 Production

    PubMed Central

    Fischer, Carrie D.; Duquette, Stephanie C.; Renaux, Bernard S.; Feener, Troy D.; Morck, Douglas W.; Hollenberg, Morley D.; Lucas, Merlyn J.

    2014-01-01

    The accumulation of neutrophils and proinflammatory mediators, such as leukotriene B4 (LTB4), is a classic marker of inflammatory disease. The clearance of apoptotic neutrophils, inhibition of proinflammatory signaling, and production of proresolving lipids (including lipoxins, such as lipoxin A4 [LXA4]) are imperative for resolving inflammation. Tulathromycin (TUL), a macrolide used to treat bovine respiratory disease, confers immunomodulatory benefits via mechanisms that remain unclear. We recently reported the anti-inflammatory properties of TUL in bovine phagocytes in vitro and in Mannheimia haemolytica-challenged calves. The findings demonstrated that this system offers a powerful model for investigating novel mechanisms of pharmacological immunomodulation. In the present study, we examined the effects of TUL in a nonbacterial model of pulmonary inflammation in vivo and characterized its effects on lipid signaling. In bronchoalveolar lavage (BAL) fluid samples from calves challenged with zymosan particles (50 mg), treatment with TUL (2.5 mg/kg of body weight) significantly reduced pulmonary levels of LTB4 and prostaglandin E2 (PGE2). In calcium ionophore (A23187)-stimulated bovine neutrophils, TUL inhibited phospholipase D (PLD), cytosolic phospholipase A2 (PLA2) activity, and the release of LTB4. In contrast, TUL promoted the secretion of LXA4 in resting and A23187-stimulated neutrophils, while levels of its precursor, 15(S)-hydroxyeicosatetraenoic acid [15(S)-HETE], were significantly lower. These findings indicate that TUL directly modulates lipid signaling by inhibiting the production of proinflammatory eicosanoids and promoting the production of proresolving lipoxins. PMID:24820086

  2. Development of a one-run real-time PCR detection system for pathogens associated with bovine respiratory disease complex

    PubMed Central

    KISHIMOTO, Mai; TSUCHIAKA, Shinobu; RAHPAYA, Sayed Samim; HASEBE, Ayako; OTSU, Keiko; SUGIMURA, Satoshi; KOBAYASHI, Suguru; KOMATSU, Natsumi; NAGAI, Makoto; OMATSU, Tsutomu; NAOI, Yuki; SANO, Kaori; OKAZAKI-TERASHIMA, Sachiko; OBA, Mami; KATAYAMA, Yukie; SATO, Reiichiro; ASAI, Tetsuo; MIZUTANI, Tetsuya

    2017-01-01

    Bovine respiratory disease complex (BRDC) is frequently found in cattle worldwide. The etiology of BRDC is complicated by infections with multiple pathogens, making identification of the causal pathogen difficult. Here, we developed a detection system by applying TaqMan real-time PCR (Dembo respiratory-PCR) to screen a broad range of microbes associated with BRDC in a single run. We selected 16 bovine respiratory pathogens (bovine viral diarrhea virus, bovine coronavirus, bovine parainfluenza virus 3, bovine respiratory syncytial virus, influenza D virus, bovine rhinitis A virus, bovine rhinitis B virus, bovine herpesvirus 1, bovine adenovirus 3, bovine adenovirus 7, Mannheimia haemolytica, Pasteurella multocida, Histophilus somni, Trueperella pyogenes, Mycoplasma bovis and Ureaplasma diversum) as detection targets and designed novel specific primer-probe sets for nine of them. The assay performance was assessed using standard curves from synthesized DNA. In addition, the sensitivity of the assay was evaluated by spiking solutions extracted from nasal swabs that were negative by Dembo respiratory-PCR for nucleic acids of pathogens or synthesized DNA. All primer-probe sets showed high sensitivity. In this study, a total of 40 nasal swab samples from cattle on six farms were tested by Dembo respiratory-PCR. Dembo respiratory-PCR can be applied as a screening system with wide detection targets. PMID:28070089

  3. Treatment of naturally occurring bovine respiratory disease in juvenile calves with a single administration of a florfenicol plus flunixin meglumine formulation.

    PubMed

    Thiry, J; González-Martín, J V; Elvira, L; Pagot, E; Voisin, F; Lequeux, G; Weingarten, A; de Haas, V

    2014-04-26

    The efficacy and safety of a florfenicol plus flunixin meglumine formulation in the treatment of respiratory disease was evaluated in calves less than six weeks of age, compared with a positive control group treated with a well-established florfenicol formulation. A total of 210 calves, selected from nine sites in Belgium, France and Spain, showing severe signs of respiratory disease, were randomly assigned to treatment with either florfenicol plus flunixin meglumine (Resflor; MSD Animal Health) or florfenicol (Nuflor; MSD Animal Health), both administered subcutaneously once. Animals were clinically observed daily for 10 days following treatment initiation. The predominant respiratory pathogens were Pasteurella multocida, Mycoplasma bovis, Mannheimia haemolytica and Histophilus somni. All isolates were subject to in vitro sensitivity testing and found susceptible to florfenicol. In both groups, rectal temperature dropped and clinical index (depression and respiratory signs) significantly improved after treatment. Specifically, for the change in rectal temperature from pretreatment to six hours post-treatment, the florfenicol-flunixin formulation was found significantly superior to florfenicol. Moreover, the florfenicol-flunixin formulation alleviated the clinical signs of disease more rapidly, and was demonstrated to be non-inferior to florfenicol on days 4 and 10. The use of the product combining florfenicol and flunixin in calves is safe and efficacious in the treatment of outbreaks of bovine respiratory disease.

  4. Isolation of an adenovirus and an adeno-associated virus from goat kids with enteritis.

    PubMed

    Olson, Erik J; Haskell, Scott R R; Frank, Rodney K; Lehmkuhl, Howard D; Hobbs, Lea Ann; Warg, Janet V; Landgraf, John G; Wünschmann, Arno

    2004-09-01

    A dairy goat operation in Minnesota experienced a sudden, markedly increased mortality among its neonatal goats. Approximately 60 of 130 kids (46%) died. The animals had diarrhea and dyspnea of 1-2 days duration before death. Necropsy of 4 goat kids revealed marked, acute, catarrhal enteritis and fibrinous pleuropneumonia. Mannheimia haemolytica was isolated from the lungs. Basophilic inclusion bodies filling the entire nucleus were present in enterocytes of the ileum of 3 goats. Adenoviral particles were detected in the feces by electron microscopy and adenovirus was subsequently isolated from the intestinal content together with a parvo-like virus (dependovirus). Morphology, physicochemical characteristics, and neutralization tests indicated that the adenovirus resembled ovine adenovirus-2 (OAdV-2). However, the PstI restriction endonuclease pattern produced by the goat adenovirus was distinct from that of OAdV-2. This is the first report of enteritis in goats with an adenovirus antigenically related to OAdV-2 and with a parvo-like dependovirus.

  5. Identification of an immunogenic protein of Actinobacillus seminis that is present in microvesicles

    PubMed Central

    2006-01-01

    Abstract Actinobacillus seminis is a gram-negative bacterium of the Pasteurellaceae family that is involved in ovine epididymitis. Looking for a protein specific to this species, we determined the protein profile of subcellular fractions of A. seminis (American Type Culture Collection number 15768): proteins from the outer membrane (OMPs), inner membrane (IMPs), and cytoplasm (CPs). These profiles provide the first data, to our knowledge, regarding subcellular fractions of A. seminis. In the OMP fraction, we identified a protein with a molecular mass of 75 kDa that proved to be immunogenic and apparently specific for A. seminis. This conclusion was based on the reaction of hyperimmune serum of rabbits inoculated with whole cells of A. seminis that was tested against sonicated complete cells of reference strains and field isolates of Brucella ovis, Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni. No protein of these bacteria cross-reacted with the 75-kDa protein of A. seminis. Furthermore, when each type of hyperimmune serum was tested against the sonicated cells and each of the subcellular fractions of A. seminis, it did not recognize the A. seminis 75-kDa protein. We also isolated and identified this protein in microvesicles released to the culture supernatant. The results suggest that the 75-kDa protein could be used to establish a diagnostic test specific for ovine epididymitis caused by A. seminis. PMID:16548331

  6. Safety, bioavailability and mechanism of action of nitric oxide to control Bovine Respiratory Disease Complex in calves entering a feedlot.

    PubMed

    Regev-Shoshani, G; Vimalanathan, S; Prema, D; Church, J S; Reudink, M W; Nation, N; Miller, C C

    2014-04-01

    Bovine Respiratory Disease Complex (BRDc), a multi-factorial disease, negatively impacts the cattle industry. Nitric oxide (NO), a naturally occurring molecule, may have utility controlling incidence of BRDc. Safety, bioavailability, toxicology and tolerance/stress of administering NO to cattle is evaluated herein. Thirteen, crossbred, multiple-sourced, commingled commercial weaned beef calves were treated multiple times intranasally over a 4 week period with either a nitric oxide releasing solution (treatment) or saline (control). Exhaled NO, methemoglobin percent (MetHg) and serum nitrites demonstrated biological availability as a result of treatment. Cortisol levels, tissue nitrites, behavior and gross and macroscopic pathology of organs were all normal. Moreover, preliminary in vitro studies using Mannheimia haemolytica, Infectious Bovine Rhinotracheitis, Bovine Parainfluenza-3 and Bovine Respiratory Syncytial Virus, suggest a potential explanation for the previously demonstrated efficacy for BRDc. These data confirm the bioavailability, safety and lack of residual of NO treatment to cattle, along with the bactericidal and virucidal effects. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Respiratory syncytial virus infection in cattle.

    PubMed

    Sacco, R E; McGill, J L; Pillatzki, A E; Palmer, M V; Ackermann, M R

    2014-03-01

    Bovine respiratory syncytial virus (RSV) is a cause of respiratory disease in cattle worldwide. It has an integral role in enzootic pneumonia in young dairy calves and summer pneumonia in nursing beef calves. Furthermore, bovine RSV infection can predispose calves to secondary bacterial infection by organisms such as Mannheimia haemolytica, Pasteurella multocida, and Histophilus somni, resulting in bovine respiratory disease complex, the most prevalent cause of morbidity and mortality among feedlot cattle. Even in cases where animals do not succumb to bovine respiratory disease complex, there can be long-term losses in production performance. This includes reductions in feed efficiency and rate of gain in the feedlot, as well as reproductive performance, milk production, and longevity in the breeding herd. As a result, economic costs to the cattle industry from bovine respiratory disease have been estimated to approach $1 billion annually due to death losses, reduced performance, and costs of vaccinations and treatment modalities. Human and bovine RSV are closely related viruses with similarities in histopathologic lesions and mechanisms of immune modulation induced following infection. Therefore, where appropriate, we provide comparisons between RSV infections in humans and cattle. This review article discusses key aspects of RSV infection of cattle, including epidemiology and strain variability, clinical signs and diagnosis, experimental infection, gross and microscopic lesions, innate and adaptive immune responses, and vaccination strategies.

  8. Histophilus somni causes extracellular trap formation by bovine neutrophils and macrophages.

    PubMed

    Hellenbrand, Katrina M; Forsythe, Katelyn M; Rivera-Rivas, Jose J; Czuprynski, Charles J; Aulik, Nicole A

    2013-01-01

    Histophilus somni (formerly Haemophilus somnus) is a Gram-negative pleomorphic coccobacillus that causes respiratory, reproductive, cardiac and neuronal diseases in cattle. H. somni is a member of the bovine respiratory disease complex that causes severe bronchopneumonia in cattle. Previously, it has been reported that bovine neutrophils and macrophages have limited ability to phagocytose and kill H. somni. Recently, it was discovered that bovine neutrophils and macrophages produce extracellular traps in response to Mannheimia haemolytica, another member of the bovine respiratory disease complex. In this study, we demonstrate that H. somni also causes extracellular trap production by bovine neutrophils in a dose- and time-dependent manner, which did not coincide with the release of lactate dehydrogenase, a marker for necrosis. Neutrophil extracellular traps were produced in response to outer membrane vesicles, but not lipooligosacchride alone. Using scanning electron microscopy and confocal microscopy, we observed H. somni cells trapped within a web-like structure. Further analyses demonstrated that bovine neutrophils trapped and killed H. somni in a DNA-dependent manner. Treatment of DNA extracellular traps with DNase I freed H. somni cells and diminished bacterial death. Treatment of bovine monocyte-derived macrophages with H. somni cells also caused macrophage extracellular trap formation. These findings suggest that extracellular traps may play a role in the host response to H. somni infection in cattle. Copyright © 2012 Elsevier Ltd. All rights reserved.

  9. Respiratory disease associated with bovine coronavirus infection in cattle herds in Southern Italy.

    PubMed

    Decaro, Nicola; Campolo, Marco; Desario, Costantina; Cirone, Francesco; D'Abramo, Maria; Lorusso, Eleonora; Greco, Grazia; Mari, Viviana; Colaianni, Maria Loredana; Elia, Gabriella; Martella, Vito; Buonavoglia, Canio

    2008-01-01

    Four outbreaks of bovine respiratory disease (BRD) associated with bovine coronavirus (BCoV) infection in Italian cattle herds were reported. In 3 outbreaks, BRD was observed only in 2-3-month-old feedlot calves, whereas in the remaining outbreak, lactating cows, heifers, and calves were simultaneously affected. By using reverse transcription polymerase chain reaction (RT-PCR), BCoV RNA was detected in all outbreaks without evidence of concurrent viral pathogens (i.e., bovine respiratory syncytial virus, bovine herpesvirus type 1, bovine viral diarrhea virus, bovine parainfluenza virus). Common bacteria of cattle were recovered only from 2 outbreaks of BRD: Staphylococcus spp. and Proteus mirabilis (outbreak 1) and Mannheimia haemolytica (outbreak 4). A recently established real-time RT-PCR assay showed that viral RNA loads in nasal secretions ranged between 3.10 x 10(2) and 7.50 x 10(7) RNA copies/microl of template. Bovine coronavirus was isolated from respiratory specimens from all outbreaks except outbreak 1, in which real-time RT-PCR found very low viral titers in nasal swabs.

  10. Epizootic pneumonia of bighorn sheep following experimental exposure to Mycoplasma ovipneumoniae.

    PubMed

    Besser, Thomas E; Cassirer, E Frances; Potter, Kathleen A; Lahmers, Kevin; Oaks, J Lindsay; Shanthalingam, Sudarvili; Srikumaran, Subramaniam; Foreyt, William J

    2014-01-01

    Bronchopneumonia is a population limiting disease of bighorn sheep (Ovis canadensis). The cause of this disease has been a subject of debate. Leukotoxin expressing Mannheimia haemolytica and Bibersteinia trehalosi produce acute pneumonia after experimental challenge but are infrequently isolated from animals in natural outbreaks. Mycoplasma ovipneumoniae, epidemiologically implicated in naturally occurring outbreaks, has received little experimental evaluation as a primary agent of bighorn sheep pneumonia. In two experiments, bighorn sheep housed in multiple pens 7.6 to 12 m apart were exposed to M. ovipneumoniae by introduction of a single infected or challenged animal to a single pen. Respiratory disease was monitored by observation of clinical signs and confirmed by necropsy. Bacterial involvement in the pneumonic lungs was evaluated by conventional aerobic bacteriology and by culture-independent methods. In both experiments the challenge strain of M. ovipneumoniae was transmitted to all animals both within and between pens and all infected bighorn sheep developed bronchopneumonia. In six bighorn sheep in which the disease was allowed to run its course, three died with bronchopneumonia 34, 65, and 109 days after M. ovipneumoniae introduction. Diverse bacterial populations, predominantly including multiple obligate anaerobic species, were present in pneumonic lung tissues at necropsy. Exposure to a single M. ovipneumoniae infected animal resulted in transmission of infection to all bighorn sheep both within the pen and in adjacent pens, and all infected sheep developed bronchopneumonia. The epidemiologic, pathologic and microbiologic findings in these experimental animals resembled those seen in naturally occurring pneumonia outbreaks in free ranging bighorn sheep.

  11. Transmission of lungworms (Muellerius capillaris) from domestic goats to bighorn sheep on common pasture.

    PubMed

    Foreyt, William J; Jenkins, E J; Appleyard, G D

    2009-04-01

    Four domestic goats (Capra hircus) that were passing first-stage dorsal-spined larvae of Muellerius capillaris were copastured on a 0.82-ha pasture for 11 mo from May 2003 to April 2004 with seven Rocky Mountain bighorn sheep (Ovis canadensis) that were not passing dorsal-spined larvae. During the 11-mo experiment, two bighorn sheep died from pneumonia caused by Mannheimia (Pasteurella) haemolytica biotype A, serotype 2. The remaining five bighorn sheep and the four domestic goats remained healthy throughout the experiment. Muellerius larvae were detected from all domestic goats on a monthly basis throughout the experiment and were first detected from all five surviving bighorn sheep approximately 5 mo after the copasturing began. Once the bighorn sheep began passing Muellerius larvae, larvae were detected in low numbers from all bighorn sheep every month thereafter for the 6 mo the goats were still in the enclosure and continued to pass larvae for more than 3 yr after the goats were removed from the experiment. Six bighorn sheep in two similar enclosures that did not contain goats did not pass Muellerius larvae before, during, or after the experimental period. Results of this experiment indicate that M. capillaris from domestic goats is capable of infecting bighorn sheep when animals are copastured together on a common range.

  12. Molecular cloning, characterization and in vitro expression of SERPIN B1 of bighorn sheep (Ovis canadensis) and domestic sheep (Ovis aries), and comparison with that of other species.

    PubMed

    Subramaniam, Renuka; Dassanayake, Rohana P; Norimine, Junzo; Brown, Wendy C; Knowles, Donald P; Srikumaran, Subramaniam

    2010-10-15

    Mannheimia haemolytica infection results in enhanced PMN-mediated tissue damage in the lungs of bighorn sheep (BHS) compared to that of domestic sheep (DS). SERPIN B1 is an inhibitor of PMN-derived serine proteases. It prevents lung tissue injury by inhibiting the serine proteases released as a result of PMN lysis and degranulation. It is conceivable that PMNs of BHS exhibit decreased quantity and/or activity of SERPIN B1 which results in enhanced tissue injury and decreased bacterial clearance in pneumonic lungs of BHS. The objective of this study was to clone and express SERPIN B1 of BHS and DS, and develop antibodies to facilitate quantification of SERPIN B1. The 1,134bp cDNA of SERPIN B1 of BHS and DS encodes a polypeptide of 377 amino acids. SERPIN B1 of BHS and DS exhibits 100% identity at the nucleotide and amino acid levels. The amino acid sequence of ovine (BHS/DS) SERPIN B1 displays 69%, 71%, 74%, 78% and 80% identity with that of rats, dogs, mice, humans and horses, respectively. Ovine SERPIN B1 expressed in Escherichia coli was used to develop polyclonal antibodies in mice. Western blot analysis revealed the specificity of these antibodies for ovine rSERPIN B1. (c) 2010 Elsevier B.V. All rights reserved.

  13. CD11b of Ovis canadensis and Ovis aries: molecular cloning and characterization.

    PubMed

    Lawrence, Paulraj K; Srikumaran, Subramaniam

    2007-10-15

    Leukotoxin (Lkt) is the primary virulence factor secreted by Mannheimia haemolytica which causes pneumonia in ruminants. Previously, we have shown that CD18, the beta subunit of beta(2) integrins, mediates Lkt-induced cytolysis of ruminant leukocytes. CD18 associates with four distinct alpha subunits giving rise to four beta(2) integrins, CD11a/CD18 (LFA-1), CD11b/CD18 (Mac-1), CD11c/CD18 (CR4), and CD11d/CD18. It is not known whether all the beta(2) integrins serve as a receptor for Lkt. Since PMNs are the leukocyte subset that is most susceptible to Lkt, and Mac-1 expression on PMNs exceeds that of other beta(2) integrins, it is of interest to determine whether Mac-1 serves as a receptor for Lkt which necessitates the cloning of CD11b and CD18. In this study, we cloned and sequenced the cDNA encoding CD11b of Ovis canadensis (bighorn sheep) and Ovis aries (domestic sheep). CD11b cDNA is 3455 nucleotides long encoding a polypeptide of 1152 amino acids. CD11b polypeptides from these two species exhibit 99% identity with each other, and 92% with that of cattle, and 70-80% with that of the non-ruminants analyzed.

  14. Bacteriology and somatic cell counts in milk samples from ewes on a Scottish farm.

    PubMed

    Hariharan, Harry; Donachie, Willie; Macaldowie, Colin; Keefe, Greg

    2004-07-01

    Milk samples from 50 sheep on a single Scottish research farm were collected weekly for 10 wk postpartum. Samples were analyzed for somatic cell counts (SCC) each week and bacteriologic culture was done for 7 of the 10 wk. A total of 492 udder half samples were cultured, of which 467 had corresponding cell count data. Statistical analysis on complete SCC and culture data showed no association between SCC and bacterial isolation, even when more than 10 colonies of a single bacterial species were present. Only 3.6% of the samples were simultaneously positive for high count (> 10 colonies from 0.01 mL of milk) of any one bacterial species and high SCC (> 1 x 10(6)/mL). The bacteria recovered were: Staphylococcus equorum (19 times), S. xylosus (7 times), S. simulans (6 times), Streptococcus uberis (3 times) and other streptococci (4 times), Mannheimia (Pasteurella) haemolytica (2 times), Staphylococcus aureus (1 time), S. capitis (1 time), and Enterococcus faecium (1 time). There was an association between the test day and SCC, with higher SCC values in the first 2 wk. In addition, significantly higher SCC values were found in the oldest animals compared to the other age groups.

  15. Urethral polyp in a 1-month-old child.

    PubMed

    Beluffi, Giampiero; Berton, Francesca; Gola, Giada; Chiari, Giorgio; Romano, Piero; Cassani, Ferdinando

    2005-07-01

    Urethral polyps are a rare finding in children, particularly in the very young. They are suspected by the presence of various clinical signs such as obstruction, voiding dysfunction and haematuria. There is an association with other urinary tract congenital anomalies. They are usually benign fibro-epithelial lesions with no tendency to recur and are treated by surgical ablation, fulguration or laser therapy. We report a 1-month-old boy with an antenatally diagnosed left ectopic pelvic kidney, postnatal urinary tract infection and no clinical signs of obstruction. Voiding cystourethrography to exclude vesico-ureteric reflux showed a trabeculated bladder and a mobile filling defect in the posterior urethra. Owing to its large size, cystotomy was necessary to remove the polyp successfully.

  16. Loss analysis of a 1 MW class HTS synchronous motor

    NASA Astrophysics Data System (ADS)

    Baik, S. K.; Kwon, Y. K.; Kim, H. M.; Lee, J. D.; Kim, Y. C.; Park, H. J.; Kwon, W. S.; Park, G. S.

    2009-03-01

    The HTS (High-Temperature Superconducting) synchronous motor has advantages over the conventional synchronous motor such as smaller size and higher efficiency. Higher efficiency is due to smaller loss than the conventional motor, so it is important to do loss analysis in order to develop a machine with higher efficiency. This paper deals with machine losses those are dissipated in each part of a HTS synchronous motor. These losses are analyzed theoretically and compared with loss data obtained from experimental results of a 1 MW class HTS synchronous motor. Each machine loss is measured based on IEEE 115 standard and the results are analyzed and considered based on the manufacturing of the test machine.

  17. Operating nanoliter scale NMR microcoils in a 1 tesla field

    NASA Astrophysics Data System (ADS)

    McDowell, Andrew F.; Adolphi, Natalie L.

    2007-09-01

    Microcoil probes enclosing sample volumes of 1.2, 3.3, 7.0, and 81 nanoliters are constructed as nuclear magnetic resonance (NMR) detectors for operation in a 1 tesla permanent magnet. The probes for the three smallest volumes utilize a novel auxiliary tuning inductor for which the design criteria are given. The signal-to-noise ratio (SNR) and line width of water samples are measured. Based on the measured DC resistance of the microcoils, together with the calculated radio frequency (RF) resistance of the tuning inductor, the SNR is calculated and shown to agree with the measured values. The details of the calculations indicate that the auxiliary inductor does not degrade the NMR probe performance. The diameter of the wire used to construct the microcoils is shown to affect the signal line widths.

  18. Pulmonary toxicity of cyclophosphamide: a 1-year study

    SciTech Connect

    Morse, C.C.; Sigler, C.; Lock, S.; Hakkinen, P.J.; Haschek, W.M.; Witschi, H.P.

    1985-01-01

    The development of cyclophosphamide-induced pulmonary lesions over a 1-year period was studied in mice. Male BALB/c mice received a single intraperitoneal injection of 100 mg/kg of cyclophosphamide. Within 3 weeks there were scattered foci of intraalveolar foamy macrophages. With time, these foci increased in size and, 1 year later, occupied large areas in all lung lobes. There was also diffuse interstitial fibrosis. Chemical determination done 3, 12, 24, and 52 weeks after cyclophosphamide showed that lungs of animals treated with cyclophosphamide had significantly more hydroxyproline per lung than controls. One year after cyclophosphamide pressure - volume curves measured in vivo were shifted down and to the right and total lung volumes were decreased. A single injection of cyclophosphamide produced an irreversible and progressive pulmonary lesion. 16 references, 5 figures, 3 tables.

  19. Circuit Simulations of a 1 MV LTD for radiography.

    SciTech Connect

    Portillo, Salvador; Johnson, David L.; Leckbee, Joshua J.; Rose, David Vincent; Kim, Alexandre A.; Ziska, Derek Raymond; Chavez, Raymond; Molina, Isidro; Maenchen, John Eric

    2005-07-01

    A 1 MV linear transformer driver (LTD), capable of driving a radiographic diode load, has been built and tested. A circuit model of this accelerator has been developed using the BERTHA circuit simulation code. Simulations are compared to data from power-flow experiments utilizing a large area electron-beam diode load. Results show that the simulation model performs well in modeling the baseline operation of the accelerator. In addition, the circuit model has been used to predict several possible fault modes. Simulations of switch prefires, main capacitor failure, vacuum insulator flashover, and core saturation have been used to estimate the probability of inducing further failures and the impact on the load voltage and current.

  20. Underwater Imaging Using a 1 × 16 CMUT Linear Array

    PubMed Central

    Zhang, Rui; Zhang, Wendong; He, Changde; Zhang, Yongmei; Song, Jinlong; Xue, Chenyang

    2016-01-01

    A 1 × 16 capacitive micro-machined ultrasonic transducer linear array was designed, fabricated, and tested for underwater imaging in the low frequency range. The linear array was fabricated using Si-SOI bonding techniques. Underwater transmission performance was tested in a water tank, and the array has a resonant frequency of 700 kHz, with pressure amplitude 182 dB (μPa·m/V) at 1 m. The −3 dB main beam width of the designed dense linear array is approximately 5 degrees. Synthetic aperture focusing technique was applied to improve the resolution of reconstructed images, with promising results. Thus, the proposed array was shown to be suitable for underwater imaging applications. PMID:26938536

  1. Antineoplastic Agents 552. Oxidation of Combretastatin A-1

    PubMed Central

    Pettit, George R.; Thornhill, Andrew J.; Moser, Bryan R.; Hogan, Fiona

    2009-01-01

    The very unstable (< 10 min at rt) o-quinone (5) derived from the vicinal diphenol anticancer drug combretastatin A-1 (1) has been obtained by careful oxidation with NaIO4 and tetrabutylammonium bromide in water/dichloromethane. Immediate reaction with phenylenediamine (6) allowed o-quinone 5 to be trapped as the stable phenazine derivative (7). For further confirmation, 5 was also captured as a dimethoxyphenylenediamine-derived phenazine (11). Both phenazines 7 and 11 significantly inhibited (ED50 ~ 0.2 μg/mL) growth of the murine P388 lymphocytic leukemia cell line and provided a new SAR insight in the combretastatin series of naturally occurring anticancer drugs. PMID:18729517

  2. Study of the Comet C/2013 A1 (Siding Spring)

    NASA Astrophysics Data System (ADS)

    Vodniza, Alberto Q.; Pereira, Mario R.

    2014-11-01

    The comet called C/2013 A1 (SIDING SPRING) was discovered on January 3, 2013 in Australia. In January 28/2014, NASA announced that is preparing for the close encounter that will happen between the comet C/2013 A1 and Mars on October 19-2014. The Mission called “MAVEN” will insert in Mars orbit on september 21—2014. The comet will pass just 138,000 kilometers far from the surface of Mars. The probability that the comet collides with Mars is small but the dust particles emitted by the comet can cause damage to spacecrafts and probes that are in orbit around that planet. NASA is making preparations to take all precautions. If the comet is quite active, there will be almost no time to take security measures with Mars orbiters. For that reason NASA is already ahead of the facts. According to scientists of the "JET PROPULSION LABORATORY-JPL", dust particles spewing from the comet may be traveling at 56 km / sec in relation to the orbiters, fifty times faster than the speed of a bullet. From our Observatory, located in Pasto-Colombia, we captured several pictures, videos and astrometry data during several days. The pictures of the asteroid were captured with the following equipment: CGE PRO 1400 CELESTRON (f/11 Schmidt-Cassegrain Telescope) and STL-1001 SBIG camera. Astrometry was carried out, and we calculated the orbital elements.Summary And Conclusions: We obtained the following orbital parameters: eccentricity = 1.0003983, orbital inclination = 129.03078 deg, longitude of the ascending node = 300.99538 deg, argument of perihelion = 2.42310 deg, perihelion distance = 1.40023196 A.U. The parameters were calculated based on 20 observations (Jan 21 to April 02) with mean residual = 0.334 arcseconds. We also obtained the light curve of the body with our data (January to November/2014)Acknowledgements: The authors would like to thank to University of Narino-Pasto-Colombia.

  3. C/2013 A1 (Siding Spring): Breathtaker or nightmare?

    NASA Astrophysics Data System (ADS)

    Ye, Q.; Hui, M.

    2014-07-01

    The dynamically new comet, C/2013 A1 (Siding Spring), is to make a close approach to Mars on 2014 October 19 at 18:30 UT at a distance of ~40 Martian radii. Such an event is extremely rare (occurs once every 100,000 years) and offers a precious opportunity for the spacecraft on Mars to closely study the comet itself. However, at the same time, the high-speed meteoroids released from the comet also pose a threat to physically damage the spacecraft. Here we report our observations and modeling results of C/Siding Spring for characterizing the comet and assessing the risk posed to the spacecraft on Mars. We find that the optical tail of C/Siding Spring is dominated by larger particles at the time of the observation. By parameterizing the dust activity with a semi-analytic model, we find that the ejection speed of C/Siding Spring is comparable to comets such as the Rosetta target, 67P/Churyumov-Gerasimenko. Under nominal situation, the simulated dust cone will miss the planet by about 20 Martian radii. At the extreme ends of the uncertainties, the simulated dust cone will engulf Mars, but the meteoric influx at Mars is still comparable to the nominal sporadic influx, seemingly indicating that an intense and enduring meteoroid bombardment due to C/Siding Spring is unlikely.

  4. Crystal structure and absolute configuration of preaustinoid A1

    PubMed Central

    Stierle, Andrea; Stierle, Donald; Decato, Daniel

    2015-01-01

    The absolute structure of the title compound preaustinoid A1 [systematic name: (5aR,7aS,8R,10S,12R,13aR,13bS)-methyl 10-hy­droxy-5,5,7a,10,12,13b-hexa­methyl-14-methyl­ene-3,9,11-trioxohexa­deca­hydro-8,12-methano­cyclo­octa­[3,4]benzo[1,2-c]oxepine-8-carboxyl­ate], C26H36O7, has been determined by resonant scattering using Cu Kα radiation [Flack parameter = 0.07 (15)]. The structure is consistent with that reported previously [Stierle et al. (2011). J. Nat. Prod. 74, 2272–2277], determined by detailed analysis of MS and NMR data. The mol­ecule consists of a fused four-ring arrangement. The seven-membered oxepan-2-one ring has a chair conformation, as do the central cyclo­hexane rings, while the outer cyclo­hexa-1,3-dione ring has a boat conformation. In the crystal, mol­ecules are linked via O—H⋯O hydrogen bonds, forming helical chains propagating along [100]. PMID:26396816

  5. A +1 ribosomal frameshifting motif prevalent among plant amalgaviruses.

    PubMed

    Nibert, Max L; Pyle, Jesse D; Firth, Andrew E

    2016-11-01

    Sequence accessions attributable to novel plant amalgaviruses have been found in the Transcriptome Shotgun Assembly database. Sixteen accessions, derived from 12 different plant species, appear to encompass the complete protein-coding regions of the proposed amalgaviruses, which would substantially expand the size of genus Amalgavirus from 4 current species. Other findings include evidence for UUU_CGN as a +1 ribosomal frameshifting motif prevalent among plant amalgaviruses; for a variant version of this motif found thus far in only two amalgaviruses from solanaceous plants; for a region of α-helical coiled coil propensity conserved in a central region of the ORF1 translation product of plant amalgaviruses; and for conserved sequences in a C-terminal region of the ORF2 translation product (RNA-dependent RNA polymerase) of plant amalgaviruses, seemingly beyond the region of conserved polymerase motifs. These results additionally illustrate the value of mining the TSA database and others for novel viral sequences for comparative analyses. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  6. A 1-Joule laser for a 16-fiber injection system

    SciTech Connect

    Honig, J

    2004-04-06

    A 1-J laser was designed to launch light down 16, multi-mode fibers (400-{micro}m-core dia.). A diffractive-optic splitter was designed in collaboration with Digital Optics Corporation (DOC), and was delivered by DOC. Using this splitter, the energy injected into each fiber varied <1%. The spatial profile out of each fiber was such that there were no ''hot spots,'' a flyer could successfully be launched and a PETN pellet could be initiated. Preliminary designs of the system were driven by system efficiency where a pristine TEM{sub 00} laser beam would be required. The laser is a master oscillator, power amplifier (MOPA) consisting of a 4-mm-dia. Nd:YLF rod in the stable, q-switched oscillator and a 9.5-mm-dia. Nd:YLF rod in the double-passed amplifier. Using a TEM{sub 00} oscillator beam resulted in excellent transmission efficiencies through the fibers at lower energies but proved to be quite unreliable at higher energies, causing premature fiber damage, flyer plate rupture, stimulated Raman scattering (SRS), and stimulated Brillouin scattering (SBS). Upon further investigation, it was found that both temporal and spatial beam formatting of the laser were required to successfully initiate the PETN. Results from the single-mode experiments, including fiber damage, SRS and SBS losses, will be presented. In addition, results showing the improvement that can be obtained by proper laser beam formatting will also be presented.

  7. Active flow control on a 1:4 car model

    NASA Astrophysics Data System (ADS)

    Heinemann, Till; Springer, Matthias; Lienhart, Hermann; Kniesburges, Stefan; Othmer, Carsten; Becker, Stefan

    2014-05-01

    Lift and drag of a passenger car are strongly influenced by the flow field around its rear end. The bluff body geometry produces a detached, transient flow which induces fluctuating forces on the body, affecting the rear axle, which may distress dynamic stability and comfort significantly. The investigations presented here deal with a 1:4 scale model of a simplified test car geometry that produces fluctuating lift and drag due to its strongly rounded rear geometry. To examine the influence of active flow control on this behavior, steady air jets were realized to exhaust from thin slots across the rear in three different configurations. Investigations were performed at and included the capturing of effective integral lift and drag, velocity measurements in the surrounding flow field with Laser Doppler Anemometry, surface pressure measurements and surface oil flow visualization on the rear. The flow field was found to be dominated by two longitudinal vortices, developing from the detachment of the flow at the upper C-pillar positions, and a recirculating, transverse vortex above the rear window. With an air jet emerging from a slot across the surface right below the rear window section, tangentially directed upstream toward the roof section, total lift could be reduced by more than 7 %, with rear axle lift reduction of about 5 % and negligible drag affection (1 %).

  8. Optimizing the Construction of the A1 Collaboration Neutron Detector

    NASA Astrophysics Data System (ADS)

    Chinn, Edward; A1 Collaboration

    2016-09-01

    We report on the design and construction of a frame designed to optimize both the time efficiency and construction quality of the large scintillator elements These elements will be assembled to form a neutron detector for use by the A1 Collaboration at the Institute for Nuclear Physics in Mainz, Germany. The design had to provide adequate support for the 20 kg scintillator bars while gluing light guides and photomultiplier tubes to both sides of the bars using optical cement. The optical cement requires approximately 24 hours to dry and 100 bars have to be glued with this apparatus. To address each of these issues, several different prototypes were designed and reviewed. The selected apparatus minimized size to meet space constraints, with reduced material cost and provided the most time-efficient way to build the neutron detector. Once the schematic design was selected, we produced technical drawings in AutoDesk Inventor. Assembled the structure and completed gluing of the first batch of scintillators, in order to verify the performance. This apparatus was successful at producing high quality scintillators which were evaluated using cosmic rays. National Science Foundation Grant No. IIA-1358175.

  9. Self Assembly of Histone F2a1

    PubMed Central

    Sperling, Ruth; Bustin, Michael

    1974-01-01

    Purified F2a1 histone molecules assemble into organized structures observable by electron microscopy. The basic structure observed at pH 8 and ionic strength of 0.15 has the shape of a bent rod with an average width of 22 Å. The average circumferential length of the rod is 220 Å and the average distance between the tips of the rod is 150 Å. When the ionic strength is increased the rods align lengthwise into intertwined fiber-like structures. In some cases bent rods assemble “face-to-face” to give circular structures. At high protein concentrations the long fibers form paracrystalline arrays. Examination of these arrays by optical diffraction yielded a meridional reflection with a spacing of 150 Å. The main additional reflections are compatible with a structure having a repeat unit of 300 Å. We suggest that in chromatin the DNA is packed around organized periodic histone structures and that the periodicity of the histone structure may dictate the periodicity of the repeating unit in chromatin. Images PMID:4531005

  10. Conceptual Design for a 1-GeV IFEL Accelerator

    NASA Astrophysics Data System (ADS)

    Kimura, W. D.; Musumeci, P.; Quimby, D. C.; Gottschalk, S. C.; Pellegrini, C.

    2004-12-01

    A conceptual design for a multistaged 1-GeV IFEL laser-driven accelerator (laser linac) was developed using the Staged Electron Laser Acceleration (STELLA) inverse free electron laser (IFEL) model created at STI Optronics. A comparison with the UCLA TREDI model yields good agreement with the STELLA model. The 1-GeV IFEL laser linac consists of an IFEL buncher for forming microbunches and four IFEL acceleration stages. Electrons enter the laser linac from a conventional microwave-driven linac (51 MeV). The acceleration stages are driven by 10-TW laser beams at 1.06-μm. It is found good trapping occurs as the electrons are accelerated; however, refocusing of the e-beam between acceleration stages is needed to control detrapping effects. The energy spread of the trapped electrons is also small. This design exercise was in support of the task placed upon the EM Structure-Based Accelerators Working Group at the 2004 Advanced Accelerator Concepts Workshop. It demonstrates that a 1-GeV IFEL laser linac is feasible with present technology.

  11. Bovine viral diarrhea virus (BVDV) 1b: predominant BVDV subtype in calves with respiratory disease

    PubMed Central

    Fulton, Robert W.; Ridpath, Julia F.; Saliki, Jeremiah T.; Briggs, Robert E.; Confer, Anthony W.; Burge, Lurinda J.; Purdy, C. W.; Loan, Raymond W.; Duff, Glenn C.; Payton, Mark E.

    2002-01-01

    The prevalence of bovine viral diarrhea virus (BVDV) infections was determined in 2 groups of stocker calves with acute respiratory disease. Both studies used calves assembled after purchase from auction markets by an order buyer and transported to feedyards, where they were held for approximately 30 d. In 1 study, the calves were mixed with fresh ranch calves from a single ranch. During the studies, at day 0 and at weekly intervals, blood was collected for viral antibody testing and virus isolation from peripheral blood leukocytes (PBLs), and nasal swabs were taken for virus isolation. Samples from sick calves were also collected. Serum was tested for antibodies to bovine herpesvirus-1 (BHV-1), BVDV1a, 1b, and 2, parainfluenza 3 virus (PI3V), and bovine respiratory syncytial virus (BRSV). The lungs from the calves that died during the studies were examined histopathologically, and viral and bacterial isolation was performed on lung homogenates. BVDV was isolated from calves in both studies; the predominant biotype was noncytopathic (NCP). Differential polymerase chain reaction (PCR) and nucleic acid sequencing showed the predominant subtype to be BVDV1b in both studies. In 1999, NCP BVDV1b was detected in numerous samples over time from 1 persistently infected calf; the calf did not seroconvert to BVDV1a or BVDV2. In both studies, BVDV was isolated from the serum, PBLs, and nasal swabs of the calves, and in the 1999 study, it was isolated from lung tissue at necropsy. BVDV was demonstrated serologically and by virus isolation to be a contributing factor in respiratory disease. It was isolated more frequently from sick calves than healthy calves, by both pen and total number of calves. BVDV1a and BVDV2 seroconversions were related to sickness in selected pens and total number of calves. In the 1999 study, BVDV-infected calves were treated longer than noninfected calves (5.643 vs 4.639 d; P = 0.0902). There was a limited number of BVDV1a isolates and, with BVDV1b

  12. Hubble Space Telescope View of Comet C/2013 A1

    NASA Astrophysics Data System (ADS)

    Li, Jian-Yang; Samarasinha, Nalin H.; Kelley, Michael S.; Farnham, Tony L.; Bodewits, Dennis; A'Hearn, Michael F.; Lisse, Carey M.; Delamere, W. A.; Mutchler, Max J.

    2014-11-01

    Comet C/2013 A1 (Siding Spring) is a dynamically new comet whose physical and chemical status should be the least evolved since the formation of cometesimals during the planetary system formation processes. Its close encounter with Mars on October 19, 2014 at a distance of 138,000 km allows for imaging its nucleus and inner coma by MRO/HiRISE at 140 m/pix resolution. Such an encounter offers us the opportunity to do cometary flyby science for a dynamically new comet for the first time ever. We observed C/Siding Spring using Hubble Space Telescope (HST) from October 2013 to March 2014 when the comet was at 4.58, 3.77, and 3.28 AU from the Sun, and will observe it again during its close encounter with Mars at 1.40 AU heliocentric distance. One of the objectives of these observations is to study the long-term evolution of the dust coma of C/Siding Spring, including its dust features and color, in order to provide context for better understanding the evolution of the activity of a dynamically new comet from the “flyby” observations during its Mars encounter. Our early observations show that C/Siding Spring’s coma contains two dust features, and the spatial distribution and temporal evolution of the color of its coma are consistent with the existence of icy grains. New observations to be performed during the encounter will reveal the evolution of the dust features and color from previously observed, as well as any newly developed features. We will report our results from the HST observations, including the preliminary results from the encounter observations.

  13. Varicella paediatric hospitalisations in Belgium: a 1-year national survey

    PubMed Central

    Blumental, Sophie; Sabbe, Martine; Lepage, Philippe

    2016-01-01

    Background Varicella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1-year period. Methods Data on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash. Results Participation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/105 person-years, with the highest impact among those 0–4 years old (global incidence and odds of hospitalisation: 79/105 person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had ≥1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/105 person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/106 and fatality ratio 0.2% among our cohort. Conclusions Varicella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium. PMID:26130380

  14. TRAPPIST monitoring of comet C/2013 A1 (Siding Spring)

    NASA Astrophysics Data System (ADS)

    Opitom, Cyrielle; Jehin, Emmanuël; Manfroid, Jean; Hutsemékers, Damien; Gillon, Michaël

    2014-11-01

    C/2013 A1 (Siding Spring) is a long period comet discovered by Robert H McNaught at Siding Spring Observatory in Australia on January 3, 2013 at 7.2 au from the Sun. This comet will make a close encounter with Mars on October 19, 2014. At this occasion the comet will be extensively observed both from Earth and from several orbiters around Mars.On September 20, 2013 when the comet was around 5 au from the Sun, we started a monitoring with the TRAPPIST robotic telescope installed at La Silla observatory [1]. A set of narrowband cometary filters designed by the NASA for the Hale-Bopp Observing Campaign [2] is permanently mounted on the telescope along with classic Johnson-Cousins B, V, Rc, and Ic filters.We observed the comet continuously at least once a week from September 20, 2013 to April 6, 2014 with broad band filters. We then recovered the comet on May 20. At this time we could detect the gas and started the observations with narrow band filters until early November, covering the close approach to Mars and the perihelion passage.We present here our first results about comet Siding Springs. From the images in the broad band filters and in the dust continuum filters we derived A(θ)fρ values [3] and studied the evolution of the comet activity with the heliocentric distance from September 20, 2013 to early November 2014. We could also detect gas since May 20, 2014. We thus derived gas production rates using a Haser model [4]. We present the evolution of gas production rates and gas production rates ratios with the heliocentric distance.Finally, we discuss the dust and gas coma morphology.

  15. Towards a 1km resolution global flood risk model

    NASA Astrophysics Data System (ADS)

    Bates, Paul; Neal, Jeff; Sampson, Chris; Smith, Andy

    2014-05-01

    Recent advances in computationally efficient numerical algorithms and new High Performance Computing architectures now make high (1-2km) resolution global hydrodynamic models a realistic proposition. However in many areas of the world the data sets and tools necessary to undertake such modelling do not currently exist. In particular, five major problems need to be resolved: (1) the best globally available terrain data (SRTM) was generated from X-band interferometric radar data which does not penetrate vegetation canopies and which has significant problems in determining ground elevations in urban areas; (2) a global river bathymetry data set does not currently exist; (3) most river channels globally are less than the smallest currently resolvable grid scale (1km) and therefore require a sub-grid treatment; (4) a means to estimate the magnitude of the T year flood at any point along the global river network does not currently exist; and (5) a large proportion of flood losses are generated by off-floodplain surface water flows which are not well represented in current hydrodynamic modelling systems. In this paper we propose solutions to each of these five issues as part of a concerted effort to develop a 1km (or better) resolution global flood hazard model. We describe the new numerical algorithms, computer architectures and computational resources used, and demonstrate solutions to the five previously intractable problems identified above. We conduct a validation study of the modelling against satellite imagery of major flooding on the Mississippi-Missouri confluence plain in the central USA before outlining a proof-of-concept regional study for SE Asia as a step towards a global scale model. For SE Asia we simulate flood hazard for ten different flood return periods over the entire Thailand, Cambodia, Vietnam, Malaysia and Laos region at 1km resolution and show that the modelling produces coherent, consistent and sensible simulations of extent and water depth.

  16. Satellite Imaging with Adaptive Optics on a 1 M Telescope

    NASA Astrophysics Data System (ADS)

    Bennet, F.; Price, I.; Rigaut, F.; Copeland, M.

    2016-09-01

    The Research School of Astronomy and Astrophysics at the Mount Stromlo Observatory in Canberra, Australia, have been developing adaptive optic (AO) systems for space situational awareness applications. We report on the development and demonstration of an AO system for satellite imaging using a 1 m telescope. The system uses the orbiting object as a natural guide star to measure atmospheric turbulence, and a deformable mirror to provide an optical correction. The AO system utilised modern, high speed and low noise EMCCD technology on both the wavefront sensor and imaging camera to achieve high performance, achieving a Strehl ratio in excess of 30% at 870 nm. Images are post processed with lucky imaging algorithms to further improve the final image quality. We demonstrate the AO system on stellar targets and Iridium satellites, achieving a near diffraction limited full width at half maximum. A specialised realtime controller allows our system to achieve a bandwidth above 100 Hz, with the wavefront sensor and control loop running at 2 kHz. The AO systems we are developing show how ground-based optical sensors can be used to manage the space environment. AO imaging systems can be used for satellite surveillance, while laser ranging can be used to determine precise orbital data used in the critical conjunction analysis required to maintain a safe space environment. We have focused on making this system compact, expandable, and versatile. We are continuing to develop this platform for other space situational awareness applications such as geosynchronous satellite astrometry, space debris characterisation, satellite imaging, and ground-to-space laser communication.

  17. Neurologic abnormalities in workers of a 1-bromopropane factory.

    PubMed

    Ichihara, Gaku; Li, Weihua; Shibata, Eiji; Ding, Xuncheng; Wang, Hailan; Liang, Yideng; Peng, Simeng; Itohara, Seiichiro; Kamijima, Michihiro; Fan, Qiyuan; Zhang, Yunhui; Zhong, Enhong; Wu, Xiaoyun; Valentine, William M; Takeuchi, Yasuhiro

    2004-09-01

    We reported recently that 1-bromopropane (1-BP; n-propylbromide, CAS Registry no. 106-94-5), an alternative to ozone-depleting solvents, is neurotoxic and exhibits reproductive toxicity in rats. The four most recent case reports suggested possible neurotoxicity of 1-BP in workers. The aim of the present study was to establish the neurologic effects of 1-BP in workers and examine the relationship with exposure levels. We surveyed 27 female workers in a 1-BP production factory and compared 23 of them with 23 age-matched workers in a beer factory as controls. The workers were interviewed and examined by neurologic, electrophysiologic, hematologic, biochemical, neurobehavioral, and postural sway tests. 1-BP exposure levels were estimated with passive samplers. Tests with a tuning fork showed diminished vibration sensation of the foot in 15 workers exposed to 1-BP but in none of the controls. 1-BP factory workers showed significantly longer distal latency in the tibial nerve than did the controls but no significant changes in motor nerve conduction velocity. Workers also displayed lower values in sensory nerve conduction velocity in the sural nerve, backward recalled digits, Benton visual memory test scores, pursuit aiming test scores, and five items of the Profile of Mood States (POMS) test (tension, depression, anxiety, fatigue, and confusion) compared with controls matched for age and education. Workers hired after May 1999, who were exposed to 1-BP only (workers hired before 1999 could have also been exposed to 2-BP), showed similar changes in vibration sense, distal latency, Benton test scores, and depression and fatigue in the POMS test. Time-weighted average exposure levels in the workers were 0.34-49.19 ppm. Exposure to 1-BP could adversely affect peripheral nerves or/and the central nervous system.

  18. Varicella paediatric hospitalisations in Belgium: a 1-year national survey.

    PubMed

    Blumental, Sophie; Sabbe, Martine; Lepage, Philippe

    2016-01-01

    Varicella universal vaccination (UV) has been implemented in many countries for several years. Nevertheless, varicella UV remains debated in Europe and few data are available on the real burden of infection. We assessed the burden of varicella in Belgium through analysis of hospitalised cases during a 1-year period. Data on children admitted to hospital with varicella were collected through a national network from November 2011 to October 2012. Inclusion criteria were either acute varicella or related complications up to 3 weeks after the rash. Participation of 101 hospitals was obtained, covering 97.7% of the total paediatric beds in Belgium. 552 children were included with a median age of 2.1 years. Incidence of paediatric varicella hospitalisations reached 29.5/10(5) person-years, with the highest impact among those 0-4 years old (global incidence and odds of hospitalisation: 79/10(5) person-years and 1.6/100 varicella cases, respectively). Only 14% (79/552) of the cohort had an underlying chronic condition. 65% (357/552) of children had ≥1 complication justifying their admission, 49% were bacterial superinfections and 10% neurological disorders. Only a quarter of children (141/552) received acyclovir. Incidence of complicated hospitalised cases was 19/10(5) person-years. Paediatric intensive care unit admission and surgery were required in 4% and 3% of hospitalised cases, respectively. Mortality among Belgian paediatric population was 0.5/10(6) and fatality ratio 0.2% among our cohort. Varicella demonstrated a substantial burden of disease in Belgian children, especially among the youngest. Our thorough nationwide study, run in a country without varicella UV, offers data to support varicella UV in Belgium. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

  19. Annexin A1 Complex Mediates Oxytocin Vesicle Transport

    PubMed Central

    Makani, Vishruti; Sultana, Rukhsana; Sie, Khin Sander; Orjiako, Doris; Tatangelo, Marco; Dowling, Abigail; Cai, Jian; Pierce, William; Butterfield, D. Allan; Hill, Jennifer; Park, Joshua

    2013-01-01

    Oxytocin is a major neuropeptide that modulates the brain functions involved in social behavior and interaction. Despite of the importance of oxytocin for neural control of social behavior, little is known about the molecular mechanism(s) by which oxytocin secretion in the brain is regulated. Pro-oxytocin is synthesized in the cell bodies of hypothalamic neurons in the supraoptic and paraventricular nuclei and processed to a 9-amino-acid mature form during post-Golgi transport to the secretion sites at the axon terminals and somatodendritic regions. Oxytocin secreted from the somatodendritic regions diffuses throughout the hypothalamus and its neighboring brain regions. Some oxytocin-positive axons innervate and secrete oxytocin to the brain regions distal to the hypothalamus. Brain oxytocin binds to its receptors in the brain regions involved in social behavior. Oxytocin is also secreted from the axon terminal at the posterior pituitary gland into the blood circulation. We have discovered a new molecular complex consisting of annexin A1 (ANXA1), A-kinase anchor protein 150 (AKAP150), and microtubule motor, that controls the distribution of oxytocin vesicles between the axon and the cell body in a protein kinase A (PKA)- and protein kinase C (PKC)-sensitive manner. ANXA1 showed significant co-localization with oxytocin vesicles. Activation of PKA enhanced the association of kinesin-2 with ANXA1, thus increasing the axon-localization of oxytocin vesicles. Conversely, activation of PKC decreased the binding of kinesin-2 to ANXA1, thus attenuating the axon-localization of oxytocin vesicles. Our study suggests that ANXA1 complex coordinates the actions of PKA and PKC to control the distribution of oxytocin vesicles between the axon and the cell body. PMID:24118254

  20. Experimental study of a 1 MW, 170 GHz gyrotron oscillator

    NASA Astrophysics Data System (ADS)

    Kimura, Takuji

    A detailed experimental study is presented of a 1 MW, 170 GHz gyrotron oscillator whose design is consistent with the ECH requirements of the International Thermonuclear Experimental Reactor (ITER) for bulk heating and current drive. This work is the first to demonstrate that megawatt power level at 170 GHz can be achieved in a gyrotron with high efficiency for plasma heating applications. Maximum output power of 1.5 MW is obtained at 170.1 GHz in 85 kV, 50A operation for an efficiency of 35%. Although the experiment at MIT is conducted with short pulses (3 μs), the gyrotron is designed to be suitable for development by industry for continuous wave operation. The peak ohmic loss on the cavity wall for 1 MW of output power is calculated to be 2.3 kW/cm2, which can be handled using present cooling technology. Mode competition problems in a highly over-moded cavity are studied to maximize the efficiency. Various aspects of electron gun design are examined to obtain high quality electron beams with very low velocity spread. A triode magnetron injection gun is designed using the EGUN simulation code. A total perpendicular velocity spread of less than 8% is realized by designing a low- sensitivity, non-adiabatic gun. The RF power is generated in a short tapered cavity with an iris step. The operating mode is the TE28,8,1 mode. A mode converter is designed to convert the RF output to a Gaussian beam. Power and efficiency are measured in the design TE28,8,1 mode at 170.1 GHz as well as the TE27,8,1 mode at 166.6 GHz and TE29,8,1 mode at 173.5 GHz. Efficiencies between 34%-36% are consistently obtained over a wide range of operating parameters. These efficiencies agree with the highest values predicted by the multimode simulations. The startup scenario is investigated and observed to agree with the linear theory. The measured beam velocity ratio is consistent with EGUN simulation. Interception of reflected beam by the mod-anode is measured as a function of velocity ratio

  1. 17 CFR 270.3a-1 - Certain prima facie investment companies.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment companies. Notwithstanding section 3(a)(1)(C) of the Act (15 U.S.C. 80a-3(a)(1)(c)), an issuer will...

  2. 17 CFR 270.3a-1 - Certain prima facie investment companies.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment companies. Notwithstanding section 3(a)(1)(C) of the Act (15 U.S.C. 80a-3(a)(1)(c)), an issuer will...

  3. 17 CFR 270.3a-1 - Certain prima facie investment companies.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment companies. Notwithstanding section 3(a)(1)(C) of the Act (15 U.S.C. 80a-3(a)(1)(c)), an issuer will...

  4. 17 CFR 270.3a-1 - Certain prima facie investment companies.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment companies. Notwithstanding section 3(a)(1)(C) of the Act (15 U.S.C. 80a-3(a)(1)(c)), an issuer will...

  5. 17 CFR 270.3a-1 - Certain prima facie investment companies.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... companies. 270.3a-1 Section 270.3a-1 Commodity and Securities Exchanges SECURITIES AND EXCHANGE COMMISSION (CONTINUED) RULES AND REGULATIONS, INVESTMENT COMPANY ACT OF 1940 § 270.3a-1 Certain prima facie investment companies. Notwithstanding section 3(a)(1)(C) of the Act (15 U.S.C. 80a-3(a)(1)(c)), an issuer will...

  6. Annexin A1 can inhibit the in vitro invasive ability of nasopharyngeal carcinoma cells possibly through Annexin A1/S100A9/Vimentin interaction

    PubMed Central

    Huang, Weiguo; Tang, Yunlian; Fu, Weiting

    2017-01-01

    Annexin A1 is a member of a large superfamily of glucocorticoid-regulated, calcium- and phospholipid-binding proteins. Our previous studies have shown that the abnormal expression of Annexin A1 is related to the occurrence and development of nasopharyngeal carcinoma (NPC). To understand the roles of Annexin A1 in the tumorigenesis of NPC, targeted proteomic analysis was performed on Annexin A1-associated proteins from NPC cells. We identified 436 proteins associated with Annexin A1, as well as two Annexin A1-interacted key proteins, S100A9 and Vimentin, which were confirmed by co-immunoprecipitation. Gene function classification revealed that the Annexin A1-associated proteins can be grouped into 21 clusters based on their molecular functions. Protein–protein interaction analysis indicated that Annexin A1 /S100A9/Vimentin interactions may be involved in the invasion and metastasis of NPC because they can form complexes in NPC cells. The down-regulation of Annexin A1 in NPC may lead to the overexpression of S100A9/Vimentin, which may increase the possibility of the invasion ability of NPC cells by adjusting the function of cytoskeleton proteins. Results suggested that the biological functions of Annexin A1 in NPC were diverse, and that Annexin A1 can inhibit the in vitro invasive ability of NPC cells through Annexin A1 /S100A9/Vimentin interaction. PMID:28355254

  7. The Collection of Ice in Jet A-1 Fuel Pipes

    NASA Astrophysics Data System (ADS)

    Maloney, Thomas C.

    Ice collection and blockages in fuel systems have been of interest to the aerospace community since their discovery in the late 1950's when a B-52 crashed. A recent growth of interest was provoked by several incidents that occurred within the last few years. This study seeks to understand the underlying principles of ice growth in fuel flow systems. Tests were performed in a recirculated fuel system with a fuel tank that held approximately 115 gallons of Jet A-1 fuel and ice accumulation was observed in two removable test pipes. The setup was in an altitude chamber capable of -60 °F and the experiments involved full scale flow components. Initially, tests were done to better understand the system and variables that effected accumulation. First, initial conditions within the test pipes were varied. Next, pipe geometry, pipe surface properties, initial water content of the fuel and heat transfer from the fuel pipe were varied. As a result of the tests, observations were made about other effects involved in the study. The effects include: the result of sequentially run tests, the effect of the fuel on the freezing temperature of the entrained water, the effect of ice accumulation on pipe welds, and the effect of the test pipe entrance and exit flow conditions on ice accumulation. The results of initial tests were qualitative. Later quantitative tests were done to demonstrate the dependence of temperature, Reynolds number, and heat transfer on ice accumulation. Tests were quantified with a pressure increase across the pipe sections that was normalized by the expected theoretical initial pressure. As a result of these tests the effect of contamination in the fuel was revealed. For ease of reference, the initial tests were called "stage I" and the later tests were called "stage II". The results of stage I showed that accumulation of soft ice was greatest when a layer of hard ice had initially formed on the pipe surface. Stainless steel collected more ice than Teflon

  8. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A transaction... section 11(a)(1) of the Act or specified in 17 CFR 240.11a1-4(T) shall be deemed to be revenue derived...

  9. Comparison of four variants of a major allergen in hazelnut (Corylus avellana) Cor a 1.04 with the major hazel pollen allergen Cor a 1.01.

    PubMed

    Lüttkopf, D; Müller, U; Skov, P S; Ballmer-Weber, B K; Wüthrich, B; Skamstrup Hansen, K; Poulsen, L K; Kästner, M; Haustein, D; Vieths, S

    2002-01-01

    The aim of this study was to produce the Bet v 1-related major hazelnut allergen Cor a 1.0401 and variants thereof as recombinant allergens, and to compare their immuno-reactivity with the major hazel pollen allergen using sera of patients whose hazelnut allergy recently was confirmed by double-blind placebo-controlled food challenges (DBPCFC) in a multicenter study. Total RNA was isolated from immature hazelnuts and transcribed into cDNA. Full length coding DNA obtained by PCR-strategy was subcloned into pTYB11 vector and expressed in E. coli ER2566 cells. Native non-fusion target proteins were purified by DTT-induced self-cleavage of the intein-tagged N-terminal fusion proteins. IgE reactivity of the recombinant allergens was tested by enzyme allergosorbent test (EAST), EAST-inhibition, immunoblot-inhibition and histamine release assays. Four recombinant allergens were produced showing deduced amino acid sequence identities among each other of 97-99%, and were considered as variants Cor a 1.0401 (GenBank Accession no.: AF136945), Cor a 1.0402 (AF323973), Cor a 1.0403 (AF323974) and Cor a 1.0404 (AF323975). Cor a 1.0402 and 03 only differed in a C4S exchange. Cor a 1.0404 had a unique proline residue in position 99. Surprisingly, only 63% identity was revealed with hazel pollen Cor a 1. EAST with 43 sera of patients with positive DBPCFC to hazelnut indicated IgE reactivity to Cor a 1.0401 in 95% of the sera, to Cor a 1.0402 in 93%, to Cor a 1.0403 in 91%, and in only 74% of the sera to the proline variant Cor a 1.0404. The allergenic activity of the four variants was confirmed by histamine release assays in 15 hazelnut-allergic patients stimulated with the four variants and controls. Eleven sera were positive with extract from native hazelnut, 13 with rCor a 1.0401, 12 with rCor a 1.0402, 11 with rCor a 1.0403, and only two with rCor a 1.0404 containing the proline exchange. The high IgE binding variant Cor a 1.0401 showed only partial IgE cross-reactivity with

  10. Acquired thermotolerance independent of heat shock factor A1 (HsfA1), the master regulator of the heat stress response.

    PubMed

    Liu, Hsiang-chin; Charng, Yee-yung

    2012-05-01

    The heat stress (HS) response in eukaryotes is mainly regulated by heat shock factors (HSFs). Genetic disruption of the master HSF gene leads to dramatically reduced HS response and thermotolerance in several model organisms. However, it is not clear whether organisms devoid of the master regulator can still acclimate to heat. Previously, we showed that Arabidopsis HsfA1a, HsfA1b, and HsfA1d act as master regulators in the HS response. In this study, we examined the heat acclimation capacity of the Arabidopsis quadruple and triple T-DNA knockout mutants of HsfA1a, HsfA1b, HsfA1d, and HsfA1e. Our data showed that in the absence of the master regulators, a minimal but significant level of acquired thermotolerance could be attained in the Arabidopsis mutants after acclimation. The optimum acclimation temperature for the HsfA1 quadruple mutant was lower than that for the wild type plants, suggesting that plant cells have two HS-sensing mechanisms that can be distinguished genetically. The acquired thermotolerance of the quadruple mutant was likely due to the induction of a small number of HsfA1-independent HS response genes regulated by other transcription factors. Here, we discuss the possible candidates and propose a working model of the transcription network of the HS response by including the HsfA1-dependent and -independent pathways.

  11. The A1 Subunit of Shiga Toxin 2 Has Higher Affinity for Ribosomes and Higher Catalytic Activity than the A1 Subunit of Shiga Toxin 1

    PubMed Central

    Basu, Debaleena; Li, Xiao-Ping; Kahn, Jennifer N.; May, Kerrie L.; Kahn, Peter C.

    2015-01-01

    Shiga toxin (Stx)-producing Escherichia coli (STEC) infections can lead to life-threatening complications, including hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS), which is the most common cause of acute renal failure in children in the United States. Stx1 and Stx2 are AB5 toxins consisting of an enzymatically active A subunit associated with a pentamer of receptor binding B subunits. Epidemiological evidence suggests that Stx2-producing E. coli strains are more frequently associated with HUS than Stx1-producing strains. Several studies suggest that the B subunit plays a role in mediating toxicity. However, the role of the A subunits in the increased potency of Stx2 has not been fully investigated. Here, using purified A1 subunits, we show that Stx2A1 has a higher affinity for yeast and mammalian ribosomes than Stx1A1. Biacore analysis indicated that Stx2A1 has faster association and dissociation with ribosomes than Stx1A1. Analysis of ribosome depurination kinetics demonstrated that Stx2A1 depurinates yeast and mammalian ribosomes and an RNA stem-loop mimic of the sarcin/ricin loop (SRL) at a higher catalytic rate and is a more efficient enzyme than Stx1A1. Stx2A1 depurinated ribosomes at a higher level in vivo and was more cytotoxic than Stx1A1 in Saccharomyces cerevisiae. Stx2A1 depurinated ribosomes and inhibited translation at a significantly higher level than Stx1A1 in human cells. These results provide the first direct evidence that the higher affinity for ribosomes in combination with higher catalytic activity toward the SRL allows Stx2A1 to depurinate ribosomes, inhibit translation, and exhibit cytotoxicity at a significantly higher level than Stx1A1. PMID:26483409

  12. Impact of glutathione-HbA1c on HbA1c measurement in diabetes diagnosis via array isoelectric focusing, liquid chromatography, mass spectrometry and ELISA.

    PubMed

    Li, Si; Guo, Chen-Gang; Chen, Lu; Yin, Xiao-Yang; Wu, Yi-Xin; Fan, Liu-Yin; Fan, Hui-Zhi; Cao, Cheng-Xi

    2013-10-15

    Hemoglobin A1c (HbA1c) has been proven to be a key biomarker for diabetes screening, and glutathiolation of HbA1c (viz., GSS-HbA1c) has been identified. However, the impact of GSS-HbA1c on the measurement of HbA1c for diabetes screening has not been quantitatively assessed yet. To address the issue, the micropreparative capillary isoelectric focusing (cIEF) developed in our previous work was used for the high resolution separation and purification of hemoglobin (Hb) species. The main fractions of HbA0, HbA3 and HbA1c extracted from the developed cIEF were identified by validated Mono S method. The proposed GSS-HbA1c fractions in the cIEF were pooled and identified by electrospray ionization mass spectrometry (ESI-MS). The HbA1c enzyme-linked immunosorbent assay (ELISA) kit was employed for further quantitative analysis of GSS-HbA1c. A total of 34 blood samples with HbA1c levels from 4.2% to 13.4% were assessed via the above comprehensive strategy of IEF-HPLC-MS-ELISA. It was demonstrated that the HbA1c levels detected by cation exchange LC were considerably influenced by the glutathiolation of Hb and the range of detected GSS-HbA1c values was between 0.23% and 0.74%. The results and developed cIEF methods have considerable significances for investigation of diabetes and clinical diagnosis.

  13. The A1 Subunit of Shiga Toxin 2 Has Higher Affinity for Ribosomes and Higher Catalytic Activity than the A1 Subunit of Shiga Toxin 1.

    PubMed

    Basu, Debaleena; Li, Xiao-Ping; Kahn, Jennifer N; May, Kerrie L; Kahn, Peter C; Tumer, Nilgun E

    2015-10-19

    Shiga toxin (Stx)-producing Escherichia coli (STEC) infections can lead to life-threatening complications, including hemorrhagic colitis (HC) and hemolytic-uremic syndrome (HUS), which is the most common cause of acute renal failure in children in the United States. Stx1 and Stx2 are AB5 toxins consisting of an enzymatically active A subunit associated with a pentamer of receptor binding B subunits. Epidemiological evidence suggests that Stx2-producing E. coli strains are more frequently associated with HUS than Stx1-producing strains. Several studies suggest that the B subunit plays a role in mediating toxicity. However, the role of the A subunits in the increased potency of Stx2 has not been fully investigated. Here, using purified A1 subunits, we show that Stx2A1 has a higher affinity for yeast and mammalian ribosomes than Stx1A1. Biacore analysis indicated that Stx2A1 has faster association and dissociation with ribosomes than Stx1A1. Analysis of ribosome depurination kinetics demonstrated that Stx2A1 depurinates yeast and mammalian ribosomes and an RNA stem-loop mimic of the sarcin/ricin loop (SRL) at a higher catalytic rate and is a more efficient enzyme than Stx1A1. Stx2A1 depurinated ribosomes at a higher level in vivo and was more cytotoxic than Stx1A1 in Saccharomyces cerevisiae. Stx2A1 depurinated ribosomes and inhibited translation at a significantly higher level than Stx1A1 in human cells. These results provide the first direct evidence that the higher affinity for ribosomes in combination with higher catalytic activity toward the SRL allows Stx2A1 to depurinate ribosomes, inhibit translation, and exhibit cytotoxicity at a significantly higher level than Stx1A1.

  14. Reperfusion-induced myocardial dysfunction is prevented by endogenous annexin-A1 and its N-terminal-derived peptide Ac-ANX-A1(2-26).

    PubMed

    Qin, Chengxue; Buxton, Keith D; Pepe, Salvatore; Cao, Anh H; Venardos, Kylie; Love, Jane E; Kaye, David M; Yang, Yuan H; Morand, Eric F; Ritchie, Rebecca H

    2013-01-01

    Annexin-A1 (ANX-A1) is an endogenous, glucocorticoid-regulated anti-inflammatory protein. The N-terminal-derived peptide Ac-ANX-A1(2-26) preserves cardiomyocyte viability, but the impact of ANX-A1-peptides on cardiac contractility is unknown. We now test the hypothesis that ANX-A1 preserves post-ischaemic recovery of left ventricular (LV) function. Ac-ANX-A1(2-26) was administered on reperfusion, to adult rat cardiomyocytes as well as hearts isolated from rats, wild-type mice and mice deficient in endogenous ANX-A1 (ANX-A1(-/-)). Myocardial viability and recovery of LV function were determined. Ischaemia-reperfusion markedly impaired both cardiomyocyte viability and recovery of LV function by 60%. Treatment with exogenous Ac-ANX-A1(2-26) at the onset of reperfusion prevented cardiomyocyte injury and significantly improved recovery of LV function, in both intact rat and wild-type mouse hearts. Ac-ANX-A1(2-26) cardioprotection was abolished by either formyl peptide receptor (FPR)-nonselective or FPR1-selective antagonists, Boc2 and cyclosporin H, but was relatively insensitive to the FPR2-selective antagonist QuinC7. ANX-A1-induced cardioprotection was associated with increased phosphorylation of the cell survival kinase Akt. ANX-A1(-/-) exaggerated impairment of post-ischaemic recovery of LV function, in addition to selective LV FPR1 down-regulation. These data represent the first evidence that ANX-A1 affects myocardial function. Our findings suggest ANX-A1 is an endogenous regulator of post-ischaemic recovery of LV function. Furthermore, the ANX-A1-derived peptide Ac-ANX-A1(2-26) on reperfusion rescues LV function, probably via activation of FPR1. ANX-A1-based therapies may thus represent a novel clinical approach for the prevention and treatment of myocardial reperfusion injury. © 2012 The Authors. British Journal of Pharmacology © 2012 The British Pharmacological Society.

  15. 16 CFR Appendix A1 to Part 305 - Refrigerators With Automatic Defrost

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 16 Commercial Practices 1 2011-01-01 2011-01-01 false Refrigerators With Automatic Defrost A1 Appendix A1 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF...) Pt. 305, App. A1 Appendix A1 to Part 305—Refrigerators With Automatic Defrost Range...

  16. 16 CFR Appendix A1 to Part 305 - Refrigerators With Automatic Defrost

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 16 Commercial Practices 1 2014-01-01 2014-01-01 false Refrigerators With Automatic Defrost A1 Appendix A1 to Part 305 Commercial Practices FEDERAL TRADE COMMISSION REGULATIONS UNDER SPECIFIC ACTS OF... (âENERGY LABELING RULEâ) Pt. 305, App. A1 Appendix A1 to Part 305—Refrigerators With Automatic...

  17. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A transaction... priority, parity, and precedence in execution to orders for the account of persons who are not members...

  18. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A transaction... priority, parity, and precedence in execution to orders for the account of persons who are not members...

  19. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A transaction... priority, parity, and precedence in execution to orders for the account of persons who are not members...

  20. 17 CFR 240.11a1-1(T) - Transactions yielding priority, parity, and precedence.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ..., parity, and precedence. 240.11a1-1(T) Section 240.11a1-1(T) Commodity and Securities Exchanges SECURITIES... (rule 11a-1) § 240.11a1-1(T) Transactions yielding priority, parity, and precedence. (a) A transaction... priority, parity, and precedence in execution to orders for the account of persons who are not members...