Science.gov

Sample records for continuous porcine alveolar

  1. Reactomes of Porcine Alveolar Macrophages Infected with Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Jiang, Zhihua; Zhou, Xiang; Michal, Jennifer J.; Wu, Xiao-Lin; Zhang, Lifan; Zhang, Ming; Ding, Bo; Liu, Bang; Manoranjan, Valipuram S.; Neill, John D.; Harhay, Gregory P.; Kehrli, Marcus E.; Miller, Laura C.

    2013-01-01

    Porcine reproductive and respiratory syndrome (PRRS) has devastated pig industries worldwide for many years. It is caused by a small RNA virus (PRRSV), which targets almost exclusively pig monocytes or macrophages. In the present study, five SAGE (serial analysis of gene expression) libraries derived from 0 hour mock-infected and 6, 12, 16 and 24 hours PRRSV-infected porcine alveolar macrophages (PAMs) produced a total 643,255 sequenced tags with 91,807 unique tags. Differentially expressed (DE) tags were then detected using the Bayesian framework followed by gene/mRNA assignment, arbitrary selection and manual annotation, which determined 699 DE genes for reactome analysis. The DAVID, KEGG and REACTOME databases assigned 573 of the DE genes into six biological systems, 60 functional categories and 504 pathways. The six systems are: cellular processes, genetic information processing, environmental information processing, metabolism, organismal systems and human diseases as defined by KEGG with modification. Self-organizing map (SOM) analysis further grouped these 699 DE genes into ten clusters, reflecting their expression trends along these five time points. Based on the number one functional category in each system, cell growth and death, transcription processes, signal transductions, energy metabolism, immune system and infectious diseases formed the major reactomes of PAMs responding to PRRSV infection. Our investigation also focused on dominant pathways that had at least 20 DE genes identified, multi-pathway genes that were involved in 10 or more pathways and exclusively-expressed genes that were included in one system. Overall, our present study reported a large set of DE genes, compiled a comprehensive coverage of pathways, and revealed system-based reactomes of PAMs infected with PRRSV. We believe that our reactome data provides new insight into molecular mechanisms involved in host genetic complexity of antiviral activities against PRRSV and lays a strong

  2. In depth global analysis of transcript abundance levels in porcine alveolar macrophages following infection with porcine reproductive and respiratory syndrome virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide and causes considerable economic loss. Infection of the primary target cells, porcine alveolar macrophages (PAMs), by PRRSV causes significant changes in their function by mechanisms that are not under...

  3. In depth global analysis of gene expression levels in porcine alveolar macrophages following infection with porcine reproductive and respiratory syndrome virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide. Infection of the preferential target cells, porcine alveolar macrophages (PAMs), by PRRSV causes significant changes in their function by mechanisms that are not understood. Serial Analysis of Gene Ex...

  4. Effect of porcine reproductive and respiratory syndrome virus on porcine alveolar macrophage function as determined using serial analysis of gene expression (SAGE)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide and causes considerable economic loss. The main target of infection is the porcine alveolar macrophage (PAM). Infection of PAM by PRRSV causes significant changes in their function by mechanisms that a...

  5. Transcription Analysis of the Porcine Alveolar Macrophage Response to Mycoplasma hyopneumoniae

    PubMed Central

    Bin, Li; Luping, Du; Bing, Sun; Zhengyu, Yu; Maojun, Liu; Zhixin, Feng; Yanna, Wei; Haiyan, Wang; Guoqing, Shao; Kongwang, He

    2014-01-01

    Mycoplasma hyopneumoniae is considered the major causative agent of porcine respiratory disease complex, occurs worldwide and causes major economic losses to the pig industry. To gain more insights into the pathogenesis of this organism, the high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages to M. hyopneumoniae infection. A total of 1033 and 1235 differentially expressed genes were identified in porcine alveolar macrophages in responses to exposure to M. hyopneumoniae at 6 and 15 hours post infection, respectively. The differentially expressed genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, cell adhesion, defense response, signal transduction, protein folding, protein ubiquitination and so on. The pathway analysis demonstrated that the most significant pathways were the chemokine signaling pathway, Toll-like receptor signaling pathway, RIG-I-like receptor signaling pathway, nucleotide-binding oligomerization domains (Nod)-like receptor signaling pathway and apoptosis signaling pathway. The reliability of the data obtained from the microarray was verified by performing quantitative real-time PCR. The expression kinetics of chemokines was further analyzed. The present study is the first to document the response of porcine alveolar macrophages to M. hyopneumoniae infection. The data further developed our understanding of the molecular pathogenesis of M. hyopneumoniae. PMID:25098731

  6. Reactomes of porcine alveolar macrophages infected with porcine reproductive and respiratory syndrome virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome (PRRS) has devastated pig industries worldwide for many years. It is caused by a small RNA virus (PRRSV), which targets almost exclusively pig monocytes or macrophages. In the present study, five SAGE (serial analysis of gene expression) libraries derive...

  7. Effect of porcine reproductive and respiratory syndrome virus infection of porcine alveolar macrophages on Toll-like receptors elicitation of type I interferon responses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Control of virus replication initially depends on rapid activation of the innate immune responses. Toll-like receptor (TLR) ligands are potent inducers of innate immunity against viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV) initiates infection in pulmonary alveolar m...

  8. Effect of porcine reproductive and respiratory syndrome virus on porcine alveolar macrophage function as determined using serial analysis of gene expression (SAGE)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide and causes considerable economic loss. The major target of infection is the alveolar macrophage (AM). Infection of AMs by PRRSV causes significant changes in their function by mechanisms that are not...

  9. Synthetic Toll-like receptor 7 ligand inhibits porcine reproductive and respiratory syndrome virus infection in primary porcine alveolar macrophages.

    PubMed

    Du, Yongkun; Du, Taofeng; Shi, Yunpeng; Zhang, Angke; Zhang, Chong; Diao, Yuwen; Jin, Guangyi; Zhou, En-Min

    2016-07-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), a common viral pathogen, causes huge annual economic losses to the swine industry worldwide. After triggering by specific ligands, the Toll-like receptor 7 (TLR7), a type of pattern-recognition receptor (PRR), induces antiviral cytokines production. Previously, we synthesized an adenine analog, designated SZU101, a TLR7-specific ligand. In this study, we assessed the inhibitory effect of SZU101 on PRRSV infection in vitro. SZU101 significantly suppressed PRRSV infection in primary porcine alveolar macrophages (PAMs) in a dose-dependent manner. Moreover, SZU101-induced inhibition involved NF-κB pathway activation in PAMs to initiate expression of TLR7-mediated cytokines and induce expression of downstream signaling IFN-stimulated genes (ISGs). Chloroquine, a TLR7 inhibitor, and BAY 11-7082, an NF-κB inhibitor, reversed both the SZU101-induced antiviral effect and induction of cytokine genes and ISGs expression. Therefore, SZU101 antiviral effects depend at least in part on TLR7-NF-κB signaling pathway. Additionally, administration of SZU101 enhanced the humoral and cell-mediated immune responses against PRRSV antigens in mice. Given these results, SZU101 holds promise as an antiviral agent and a vaccine adjuvant to prevent PRRSV infection in pigs. PMID:27079946

  10. Lipopolysaccharide modulation of a CD14-like molecule on porcine alveolar macrophages

    NASA Technical Reports Server (NTRS)

    Kielian, T. L.; Ross, C. R.; McVey, D. S.; Chapes, S. K.; Blecha, F.; Spooner, B. S. (Principal Investigator)

    1995-01-01

    Cluster of differentiation antigen 14 (CD14) functions as a receptor for lipopolysaccharide (LPS) LPS-binding protein (LBP) complexes. Because LPS has varying effects on CD14 expression in vitro, we evaluated CD14 expression in response to LPS with a fully differentiated macrophage phenotype, the alveolar macrophage. By using flow microfluorometric analysis and a radioimmunoassay with an anti-human CD14 monoclonal antibody (My4) that cross-reacts with porcine CD14, we found that macrophages stimulated with LPS for 24 h exhibited a two- to fivefold increase in CD14-like antigen compared with unstimulated cells. At low concentrations of LPS, up-regulation of the CD14-like antigen was dependent on serum; at higher concentrations of LPS, serum was not required. In the absence of serum a 10-fold higher dose of LPS (10 ng/ml) was required to increase CD14-like expression. In addition, LPS-induced CD14-like up-regulation correlated with secretion of tumor necrosis factor-alpha, regardless of serum concentration. Blockade with My4 antibody significantly inhibited LPS-induced tumor necrosis factor-alpha secretion at 1 ng/ml of LPS. However, inhibition decreased as we increased the LPS concentration, suggesting the existence of CD14-independent pathways of macrophage activation in response to LPS. Alternatively, My4 may have a lower affinity for the porcine CD14 antigen than LPS, which may have only partially blocked the LPS-LBP binding site at high concentrations of LPS. Therefore, these data suggest that LPS activation of porcine alveolar macrophages for 24 h increased CD14-like receptor expression. The degree of CD14-like up-regulation was related to LPS concentration, however, activation did not require the presence of serum at high concentrations of LPS.

  11. Matrine displayed antiviral activity in porcine alveolar macrophages co-infected by porcine reproductive and respiratory syndrome virus and porcine circovirus type 2.

    PubMed

    Sun, Na; Sun, Panpan; Lv, Haipeng; Sun, Yaogui; Guo, Jianhua; Wang, Zhirui; Luo, Tiantian; Wang, Shaoyu; Li, Hongquan

    2016-01-01

    The co-infection of porcine reproductive respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) is quite common in clinical settings and no effective treatment to the co-infection is available. In this study, we established the porcine alveolar macrophages (PAM) cells model co-infected with PRRSV/PCV2 with modification in vitro, and investigated the antiviral activity of Matrine on this cell model and further evaluated the effect of Matrine on virus-induced TLR3,4/NF-κB/TNF-α pathway. The results demonstrated PAM cells inoculated with PRRSV followed by PCV2 2 h later enhanced PRRSV and PCV2 replications. Matrine treatment suppressed both PRRSV and PCV2 infection at 12 h post infection. Furthermore, PRRSV/PCV2 co- infection induced IκBα degradation and phosphorylation as well as the translocation of NF-κB from the cytoplasm to the nucleus indicating that PRRSV/PCV2 co-infection induced NF-κB activation. Matrine treatment significantly down-regulated the expression of TLR3, TLR4 and TNF-α although it, to some extent, suppressed p-IκBα expression, suggesting that TLR3,4/NF-κB/TNF-α pathway play an important role of Matrine in combating PRRSV/PCV2 co-infection. It is concluded that Matrine possesses activity against PRRSV/PCV2 co-infection in vitro and suppression of the TLR3,4/NF-κB/TNF-α pathway as an important underlying molecular mechanism. These findings warrant Matrine to be further explored for its antiviral activity in clinical settings. PMID:27080155

  12. Matrine displayed antiviral activity in porcine alveolar macrophages co-infected by porcine reproductive and respiratory syndrome virus and porcine circovirus type 2

    PubMed Central

    Sun, Na; Sun, Panpan; Lv, Haipeng; Sun, Yaogui; Guo, Jianhua; Wang, Zhirui; Luo, Tiantian; Wang, Shaoyu; Li, Hongquan

    2016-01-01

    The co-infection of porcine reproductive respiratory syndrome virus (PRRSV) and porcine circovirus type 2 (PCV2) is quite common in clinical settings and no effective treatment to the co-infection is available. In this study, we established the porcine alveolar macrophages (PAM) cells model co-infected with PRRSV/PCV2 with modification in vitro, and investigated the antiviral activity of Matrine on this cell model and further evaluated the effect of Matrine on virus-induced TLR3,4/NF-κB/TNF-α pathway. The results demonstrated PAM cells inoculated with PRRSV followed by PCV2 2 h later enhanced PRRSV and PCV2 replications. Matrine treatment suppressed both PRRSV and PCV2 infection at 12 h post infection. Furthermore, PRRSV/PCV2 co- infection induced IκBα degradation and phosphorylation as well as the translocation of NF-κB from the cytoplasm to the nucleus indicating that PRRSV/PCV2 co-infection induced NF-κB activation. Matrine treatment significantly down-regulated the expression of TLR3, TLR4 and TNF-α although it, to some extent, suppressed p-IκBα expression, suggesting that TLR3,4/NF-κB/TNF-α pathway play an important role of Matrine in combating PRRSV/PCV2 co-infection. It is concluded that Matrine possesses activity against PRRSV/PCV2 co-infection in vitro and suppression of the TLR3,4/NF-κB/TNF-α pathway as an important underlying molecular mechanism. These findings warrant Matrine to be further explored for its antiviral activity in clinical settings. PMID:27080155

  13. Suppression of NK cell-mediated cytotoxicity against PRRSV-infected porcine alveolar macrophages in vitro.

    PubMed

    Cao, Jun; Grauwet, Korneel; Vermeulen, Ben; Devriendt, Bert; Jiang, Ping; Favoreel, Herman; Nauwynck, Hans

    2013-06-28

    The adaptive immunity against PRRSV has already been studied in depth, but only limited data are available on the innate immune responses against this pathogen. In the present study, we analyzed the interaction between porcine natural killer (NK) cells and PRRSV-infected primary porcine alveolar macrophages (PAMs), since NK cells are one of the most important components of innate immunity and PAMs are primary target cells of PRRSV infection. NK cytotoxicity assays were performed using enriched NK cells as effector cells and virus-infected or mock-inoculated PAMs as target cells. The NK cytotoxicity against PRRSV-infected PAMs was decreased starting from 6h post inoculation (hpi) till the end of the experiment (12 hpi) and was significantly lower than that against pseudorabies virus (PrV)-infected PAMs. UV-inactivated PRRSV also suppressed NK activity, but much less than infectious PRRSV. Furthermore, co-incubation with PRRSV-infected PAMs inhibited degranulation of NK cells. Finally, using the supernatant of PRRSV-infected PAMs collected at 12 hpi showed that the suppressive effect of PRRSV on NK cytotoxicity was not mediated by soluble factors. In conclusion, PRRSV-infected PAMs showed a reduced susceptibility toward NK cytotoxicity, which may represent one of the multiple evasion strategies of PRRSV. PMID:23522639

  14. Protection Of Alveolar Macrophages And MARC 145 Cells From Porcine Reproductive And Respiratory Syndrome Virus Challenge By Swine Interferon-Beta

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Interferon beta, a type I IFN, is crucial in initiating the innate immune response and in the generation of the adaptive response. This study demonstrated the capacity of swine interferon beta (swIFN beta) to protect porcine alveolar macrophages (PAM) and MARC145 cells from infection with porcine re...

  15. Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation

    PubMed Central

    Chang, Pengxiang; Kuchipudi, Suresh V.; Mellits, Kenneth H.; Sebastian, Sujith; James, Joe; Liu, Jinhua; Shelton, Holly; Chang, Kin-Chow

    2015-01-01

    Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) influenza viruses in PAM. We found that PAM were readily susceptible to initial infection with all five avian and mammalian influenza viruses but only avian viruses caused early and extensive apoptosis (by 6 h of infection) resulting in reduced virus progeny and moderated pro-inflammation. Full length viral PB1-F2 present only in avian influenza viruses is a virulence factor that targets AM for mitochondrial-associated apoptotic cell death. With the use of reverse genetics on an avian H5N1 virus, we found that full length PB1-F2 contributed to increased apoptosis and pro-inflammation but not to reduced virus replication. Taken together, we propose that early apoptosis of PAM limits the spread of avian influenza viruses and that PB1-F2 could play a contributory role in the process. PMID:26642934

  16. Early apoptosis of porcine alveolar macrophages limits avian influenza virus replication and pro-inflammatory dysregulation.

    PubMed

    Chang, Pengxiang; Kuchipudi, Suresh V; Mellits, Kenneth H; Sebastian, Sujith; James, Joe; Liu, Jinhua; Shelton, Holly; Chang, Kin-Chow

    2015-01-01

    Pigs are evidently more resistant to avian than swine influenza A viruses, mediated in part through frontline epithelial cells and alveolar macrophages (AM). Although porcine AM (PAM) are crucial in influenza virus control, their mode of control is unclear. To gain insight into the possible role of PAM in the mediation of avian influenza virus resistance, we compared the host effects and replication of two avian (H2N3 and H6N1) and three mammalian (swine H1N1, human H1N1 and pandemic H1N1) influenza viruses in PAM. We found that PAM were readily susceptible to initial infection with all five avian and mammalian influenza viruses but only avian viruses caused early and extensive apoptosis (by 6 h of infection) resulting in reduced virus progeny and moderated pro-inflammation. Full length viral PB1-F2 present only in avian influenza viruses is a virulence factor that targets AM for mitochondrial-associated apoptotic cell death. With the use of reverse genetics on an avian H5N1 virus, we found that full length PB1-F2 contributed to increased apoptosis and pro-inflammation but not to reduced virus replication. Taken together, we propose that early apoptosis of PAM limits the spread of avian influenza viruses and that PB1-F2 could play a contributory role in the process. PMID:26642934

  17. Molecular Characterization of Transcriptome-wide Interactions between Highly Pathogenic Porcine Reproductive and Respiratory Syndrome Virus and Porcine Alveolar Macrophages in vivo

    PubMed Central

    Zhou, Ping; Zhai, Shanli; Zhou, Xiang; Lin, Ping; Jiang, Tengfei; Hu, Xueying; Jiang, Yunbo; Wu, Bin; Zhang, Qingde; Xu, Xuewen; Li, Jin-ping; Liu, Bang

    2011-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) infects mainly the porcine alveolar macrophages (PAMs) and causes porcine reproductive and respiratory syndrome (PRRS). Previous studies have analyzed the global gene expression profiles of lung tissue in vivo and PAMs in vitro following infection with PRRSV, however, transcriptome-wide understanding of the interaction between highly pathogenic PRRSV (HP-PRRSV) and PAMs in vivo has not yet been established. In this study, we employed Affymetrix microarrays to investigate the gene expression patterns of PAMs isolated from Tongcheng piglets (a Chinese indigenous breed) after infection with HP-PRRSV. During the infection, Tongcheng piglets exhibited typical clinical signs, e.g. fever, asthma, coughing, anorexia, lethargy and convulsion, but displayed mild regional lung damage at 5 and 7 dpi. Microarray analysis revealed that HP-PRRSV infection has affected PAMs in expression of the important genes involved in cytoskeleton and exocytosis organization, protein degradation and folding, intracellular calcium and zinc homeostasis. Several potential antiviral strategies might be employed in PAMs, including upregulating IFN-induced genes and increasing intracellular zinc ion concentration. And inhibition of the complement system likely attenuated the lung damage during HP-PRRSV infection. Transcriptomic analysis of PAMs in vivo could lead to a better understanding of the HP-PRRSV-host interaction, and to the identification of novel antiviral therapies and genetic components of swine tolerance/susceptibility to HP-PRRS. PMID:21850204

  18. Anti-inflammatory effects of several plant extracts on porcine alveolar macrophages in vitro.

    PubMed

    Liu, Y; Song, M; Che, T M; Bravo, D; Pettigrew, J E

    2012-08-01

    Certain plant extracts are bioactive substances of some foods or traditional herbs, known to possess antioxidant, antibacterial, and perhaps immunoregulatory effects. This study investigated the in vitro anti-inflammatory effects of 7 plant extracts (anethol, capsicum oleoresin, carvacrol, cinnamaldehyde, eugenol, garlicon, and turmeric oleoresin) on porcine alveolar macrophages collected from weaned pigs (n = 6 donor pigs) by bronchoalveolar lavage. The experimental design for this assay was a 2 [with or without 1 μg lipopolysaccharide (LPS)/mL] × 5 (5 different amounts of each plant extract) factorial arrangements in a randomized complete block design. The application of plant extracts were 0, 25, 50, 100, and 200 μg/mL, except for cinnamaldehyde and turmeric oleoresin, which were 0, 2.5, 5, 10, and 20 μg/mL. The 3-(4,5-dimethylthiazol-2-yl)-2,5 diphenyltetrazolium bromide (MTT) assay was used to determine the number of live cells, Griess assay was applied to detect nitric oxide (NO) production, and ELISA was used to measure tumor necrosis factor-α (TNF-α), IL-1β, transforming growth factor-β (TGF-β), and IL-10 in the cell culture supernatants of macrophages. The LPS increased (P < 0.001) the secretion of TNF-α, IL-1β, and TGF-β. Without LPS, anethol and capsicum oleoresin increased (linear, P < 0.001) cell viability of macrophages, whereas other plant extracts reduced (linear, P < 0.001) it. Anethol, capsicum oleoresin, and carvacrol enhanced (linear, P < 0.001) the cell proliferation of LPS-treated macrophages. Without LPS, anethol, capsicum oleoresin, cinnamaldehyde, or turmeric oleoresin stimulated TNF-α secretion, whereas all plant extracts except eugenol enhanced IL-1β concentration in the supernatants of macrophages. However, all plant extracts suppressed (linear, P < 0.001) TNF-α, and all plant extracts except turmeric oleoresin decreased (linear, P < 0.05) IL-1β secretion from LPS-treated macrophages. Anethol and capsicum oleoresin

  19. Identification of Differentially Expressed Proteins in Porcine Alveolar Macrophages Infected with Virulent/Attenuated Strains of Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Zhou, Tao; Cheng, Qun; Yu, Ling-Xue; Wang, Ya-Xin; Yang, Shen; Jiang, Yi-Feng; Tong, Wu; Gao, Fei; Yu, Hai; Li, Guo-Xin; Tong, Guang-Zhi

    2014-01-01

    The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is still a serious threat to the swine industry. However, the pathogenic mechanism of HP-PRRSV remains unclear. We infected host porcine alveolar macrophages (PAMs) with the virulent HuN4 strain and the attenuated HuN4-F112 strain and then utilized fluorescent two-dimensional difference gel electrophoresis (2D-DIGE) to screen for intracellular proteins that were differentially expressed in host cells infected with the two strains. There were 153 proteins with significant different expression (P<0.01) observed, 42 of which were subjected to mass spectrometry, and 24 proteins were identified. PAM cells infected with the virulent strain showed upregulated expression of pyruvate kinase M2 (PKM2), heat shock protein beta-1 (HSPB1), and proteasome subunit alpha type 6 (PSMA6), which were downregulated in cells infected with the attenuated strain. The upregulation of PKM2 provides sufficient energy for viral replication, and the upregulation of HSPB1 inhibits host cell apoptosis and therefore facilitates mass replication of the virulent strain, while the upregulation of PSMA6 facilitates the evasion of immune surveillance by the virus. Studying on those molecules mentioned above may be able to help us to understand some unrevealed details of HP-PRRSV infection, and then help us to decrease its threat to the swine industry in the future. PMID:24465692

  20. Identification of differentially expressed proteins in porcine alveolar macrophages infected with virulent/attenuated strains of porcine reproductive and respiratory syndrome virus.

    PubMed

    Zhou, Yan-Jun; Zhu, Jian-Ping; Zhou, Tao; Cheng, Qun; Yu, Ling-Xue; Wang, Ya-Xin; Yang, Shen; Jiang, Yi-Feng; Tong, Wu; Gao, Fei; Yu, Hai; Li, Guo-Xin; Tong, Guang-Zhi

    2014-01-01

    The highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV) is still a serious threat to the swine industry. However, the pathogenic mechanism of HP-PRRSV remains unclear. We infected host porcine alveolar macrophages (PAMs) with the virulent HuN4 strain and the attenuated HuN4-F112 strain and then utilized fluorescent two-dimensional difference gel electrophoresis (2D-DIGE) to screen for intracellular proteins that were differentially expressed in host cells infected with the two strains. There were 153 proteins with significant different expression (P<0.01) observed, 42 of which were subjected to mass spectrometry, and 24 proteins were identified. PAM cells infected with the virulent strain showed upregulated expression of pyruvate kinase M2 (PKM2), heat shock protein beta-1 (HSPB1), and proteasome subunit alpha type 6 (PSMA6), which were downregulated in cells infected with the attenuated strain. The upregulation of PKM2 provides sufficient energy for viral replication, and the upregulation of HSPB1 inhibits host cell apoptosis and therefore facilitates mass replication of the virulent strain, while the upregulation of PSMA6 facilitates the evasion of immune surveillance by the virus. Studying on those molecules mentioned above may be able to help us to understand some unrevealed details of HP-PRRSV infection, and then help us to decrease its threat to the swine industry in the future. PMID:24465692

  1. Transcription analysis on response of porcine alveolar macrophages to co-infection of the highly pathogenic porcine reproductive and respiratory syndrome virus and Mycoplasma hyopneumoniae.

    PubMed

    Li, Bin; Du, Luping; Xu, Xiangwei; Sun, Bing; Yu, Zhengyu; Feng, Zhixin; Liu, Maojun; Wei, Yanna; Wang, Haiyan; Shao, Guoqing; He, Kongwang

    2015-01-22

    Porcine respiratory disease complex (PRDC) is of great concern economically, for swine producers worldwide. Co-infections with porcine reproductive and respiratory syndrome virus (PRRSV) and Mycoplasma hyopneumoniae (Mhp) are considered the major causative agents of PRDC, and responsible for mass mortality in pigs. Nevertheless, the molecular mechanisms underlying the host factors involved in pathogenesis and persistent infection have not been clearly established because of a lack of information regarding host responses following co-infection. In the current study, high throughput cDNA microarray assays were employed to evaluate host responses of porcine alveolar macrophages (PAM) to co-infection with highly pathogenic PRRSV (HP-PRRSV) and Mhp. A total of 2152 and 1760 genes were identified as being differentially expressed between the control group and PRRSV+Mhp co-infected group at 6 and 15 h post infection, respectively. The DE genes were involved in many vital functional classes, including inflammatory response, immune response, apoptosis, defense response, signal transduction. The pathway analysis demonstrated that the most significant pathways were associated with chemokine signaling pathway, cytokine, TLR, RLR and NLR signaling pathways and Jak-STAT signaling pathway. STRING analysis demonstrated that IL-1β is an integral gene in co-infections with PRRSV and Mhp. The present study is the first to document the response of PAMs to co-infection with HP-PRRSV and Mhp. The observed gene expression profile could help with the screening of potential host agents for reducing the prevalence of co-infections, and to further develop our understanding of the molecular pathogenesis associated with PRRSV and Mhp co-infection in pigs. PMID:25445346

  2. Regulation of toll-like receptors 3, 7 and 9 in porcine alveolar macrophages by different genotype 1 strains of porcine reproductive and respiratory syndrome virus.

    PubMed

    Kuzemtseva, Liudmila; de la Torre, Eugenia; Martín, Gerard; Soldevila, Ferran; Ait-Ali, Tahar; Mateu, Enric; Darwich, Laila

    2014-04-15

    The toll-like receptors (TLRs) play an important role in the innate host defense against pathogens. Endosomal TLRs, TLR3, TLR7/8, and TLR9 are involved in antiviral responses by promoting the production of antiviral cytokines such as type I interferons. Porcine reproductive and respiratory syndrome (PRRS) is an important disease causing economically high losses to the swine industry worldwide and caused by a single stranded positive sense RNA virus, known as PRRS virus (PRRSV). Studies focused on the interaction between PRRSV and TLRs are scarce. The aim of the present study was to evaluate the expression of TLR3, TLR7 and TLR9 in porcine alveolar macrophages (PAM) infected with different genotype 1 PRRSV strains previously sequenced and characterized by their ability to induce TNF-α: 3262 (TNF-α inducer), 3267 (TNF-α not inducer) and an attenuated vaccine strain (strain Deventer, PorcilisPRRS, Merck) that replicates scarcely in PAM. PAM were infected with the different PRRSV strains (at 0.1 multiplicity of infection) for 48 h or mock-stimulated with PAM supernatants. Cells were collected at different time-points (0 h, 6 h, 12 h, 24 h, 36 h, 48 h) to determine the kinetics of viral replication by quantitative RT-PCR (qRT-PCR) and the expression of TLR3, 7 and 9 by qRT-PCR, flow cytometry and indirect immunofluorescence assay. Although infection with PRRSV did not affect significantly relative levels of any TLR mRNA transcript (normalized to β-actin expression), this infection resulted in significant differences in the proportion of cells expressing TLR3. Thus, in PAM infected with PRRSV strain 3262 the proportion of TLR3+ cells significantly increased from 24h compared with the controls; in contrast strain 3267 resulted in a lower proportion of TLR3+ PAM. Interestingly, strain 3262 replicate to lower levels than 3267 at comparable post-inoculation times. For strain DV, the results indicated that this strain did not replicate substantially in PAM and did not

  3. RNA-sequence analysis of primary alveolar macrophages after in vitro infection with porcine reproductive and respiratory syndrome virus strains of differing virulence.

    PubMed

    Badaoui, Bouabid; Rutigliano, Teresa; Anselmo, Anna; Vanhee, Merijn; Nauwynck, Hans; Giuffra, Elisabetta; Botti, Sara

    2014-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) mainly infects porcine alveolar macrophages (PAMs), resulting in porcine reproductive and respiratory syndrome (PRRS) in pigs. Most of the transcriptomic studies on PAMs infected with PRRSV conducted thus far have made use of microarray technology. Here, we investigated the transcriptome of PAMs in vitro at 12 h post-infection with two European PRRSV strains characterized by low (Lelystad, LV) and high (Lena) virulence through RNA-Seq. The expression levels of genes, isoforms, alternative transcription start sites (TSS) and differential promoter usage revealed a complex pattern of transcriptional and post-transcriptional gene regulation upon infection with the two strains. Gene ontology analysis confirmed that infection of PAMs with both the Lena and LV strains affected signaling pathways directly linked to the innate immune response, including interferon regulatory factors (IRF), RIG1-like receptors, TLRs and PKR pathways. The results confirmed that interferon signaling is crucial for transcriptional regulation during PAM infection. IFN-β1 and IFN-αω, but not IFN-α, were up-regulated following infection with either the LV or Lena strain. The down-regulation of canonical pathways, such as the interplay between the innate and adaptive immune responses, cell death and TLR3/TLR7 signaling, was observed for both strains, but Lena triggered a stronger down-regulation than LV. This analysis contributes to a better understanding of the interactions between PRRSV and PAMs and outlines the differences in the responses of PAMs to strains with different levels of virulence, which may lead to the development of new PRRSV control strategies. PMID:24643046

  4. Salmonella Typhimurium induces SPI-1 and SPI-2 regulated and strain dependent downregulation of MHC II expression on porcine alveolar macrophages

    PubMed Central

    2012-01-01

    Foodborne salmonellosis is one of the most important bacterial zoonotic diseases worldwide. Salmonella Typhimurium is the serovar most frequently isolated from persistently infected slaughter pigs in Europe. Circumvention of the host’s immune system by Salmonella might contribute to persistent infection of pigs. In the present study, we found that Salmonella Typhimurium strain 112910a specifically downregulated MHC II, but not MHC I, expression on porcine alveolar macrophages in a Salmonella pathogenicity island (SPI)-1 and SPI-2 dependent way. Salmonella induced downregulation of MHC II expression and intracellular proliferation of Salmonella in macrophages were significantly impaired after opsonization with Salmonella specific antibodies prior to inoculation. Furthermore, the capacity to downregulate MHC II expression on macrophages differed significantly among Salmonella strains, independently of strain specific differences in invasion capacity, Salmonella induced cytotoxicity and altered macrophage activation status. The fact that strain specific differences in MHC II downregulation did not correlate with the extent of in vitro SPI-1 or SPI-2 gene expression indicates that other factors are involved in MHC II downregulation as well. Since Salmonella strain dependent interference with the pig’s immune response through downregulation of MHC II expression might indicate that certain Salmonella strains are more likely to escape serological detection, our findings are of major interest for Salmonella monitoring programs primarily based on serology. PMID:22694285

  5. Nephrocalcinosis associated with continuous enamel hypoplasia and severe alveolar bone loss: a case report and literature review.

    PubMed

    Ashkenazi, Malka; Rafe, Zvi; Sarnat, Haim; Levin, Liran

    2014-01-01

    Enamel-renal syndrome (ERS) is a rare manifestation of nephrocalcinosis that has been associated with generalized enamel hypoplasia. The purpose of this paper was to describe, for the first time, the association of enamel-renal syndrome with severe localized periodontal bone loss. A 13-year-old boy presented with: generalized hypoplastic enamel; intrapulpal calcifications; retention of primary teeth; delayed eruption of permanent teeth; enlarged dental-follicles; misshaped roots of permanent teeth; gingival overgrowth; severe localized alveolar bone loss; and severe malocclusion. His parents were first cousins, suggesting autosomal recessive inheritance. Further studies are necessary to clarify whether the etiology of the oral disturbances relates to the genetic defect in the dental tissue or to the continuous metabolic distress associated with renal dysfunction. Nevertheless, since nephrocalcinosis is often asymptomatic, dentists should refer children with generalized enamel hypoplasia or/and multiple intrapulpal calcifications to nephrologists. PMID:24960394

  6. RECOMBINANT SWINE INTERFERON BETA PROTECTS SWINE ALVEOLAR MACROPHAGES AND MARC 145 CELLS FROM INFECTION WITH PORCINE REPRODUCTIVE AND RESPIRATORY SYNDROME VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Swine interferon beta (swIFN beta) produced in 293 cells infected with a recombinant, replication-defective human adenovirus 5 (Ad5) encoding the swIFN beta gene was tested for antiviral activity against porcine reproductive and respiratory syndrome virus (PRRSV). Marc145 cells were incubated overni...

  7. The use of porcine digestible peptides and their continuity effect in nursery pigs.

    PubMed

    Figueroa, J; Solà-Oriol, D; Guzmán-Pino, S A; Chetrit, C; Borda, E; Pérez, J F

    2016-04-01

    A total of 552 entire male and female nursery pigs were selected to be used in 2 different experiments that aimed to study if milk ingredients can be replaced by highly preferred protein sources (Exp. 1) and if pre- and postnatal exposure of those protein ingredients through the maternal diet may increase pig performance (Exp. 2). In Exp. 1, 240 pigs were separated after weaning (28 d) into 2 groups depending on the presence of lactose in their diets. Pigs ( =120) fed diets with the precence of lactose (lactose +) were given prestarter (0-14 d) and starter (15-33 d) diets with 142 and 50 g/kg of sweet milk whey, respectively; the lactose-free group ( = 120) was offered an isoenergetic diet with 20 g/kg of porcine-digestible peptides (PDP; Palbio 62SP; Bioibérica S.A., Palafolls, Spain) and wheat replacing sweet milk whey. Choice and 1-feeder tests were performed in another group of animals ( = 72) to evaluate the preference and acceptance for both diets. Pigs preferred ( = 0.039) the lactose+ over the lactose-free diet after a 30-min choice test and consumed more ( = 0.001) lactose+ than lactose-free diet in a 1-feeder test. However, no difference ( > 0.467) in performance was observed between groups for the entire nursery period. In Exp. 2, 120 animals were obtained from sows that, during late gestation (14 d) and lactation (28 d), were fed diets containing 20 g/kg of PDP and another 120 animals were obtained from sows fed an isoenergetic diet without PDP inclusion. Placenta samples were collected at farrowing to assess the volatile compounds present in the placental fluid of sows. After weaning, all pigs received a feed containing 20 g/kg of PDP in the prestarter and starter diets. A principal components analysis of the total volatile compounds showed the exclusive presence of sulfur-containing compounds and a higher presence of terpene compounds in the placental fluid of PDP-supplemented sows. In addition, pigs coming from sows fed diets supplemented with PDP

  8. Innate immune response to a H3N2 subtype swine influenza virus in newborn porcine trachea cells, alveolar macrophages, and precision-cut lung slices

    PubMed Central

    2014-01-01

    Viral respiratory diseases remain of major importance in swine breeding units. Swine influenza virus (SIV) is one of the main known contributors to infectious respiratory diseases. The innate immune response to swine influenza viruses has been assessed in many previous studies. However most of these studies were carried out in a single-cell population or directly in the live animal, in all its complexity. In the current study we report the use of a trachea epithelial cell line (newborn pig trachea cells – NPTr) in comparison with alveolar macrophages and lung slices for the characterization of innate immune response to an infection by a European SIV of the H3N2 subtype. The expression pattern of transcripts involved in the recognition of the virus, interferon type I and III responses, and the host-response regulation were assessed by quantitative PCR in response to infection. Some significant differences were observed between the three systems, notably in the expression of type III interferon mRNA. Then, results show a clear induction of JAK/STAT and MAPK signaling pathways in infected NPTr cells. Conversely, PI3K/Akt signaling pathways was not activated. The inhibition of the JAK/STAT pathway clearly reduced interferon type I and III responses and the induction of SOCS1 at the transcript level in infected NPTr cells. Similarly, the inhibition of MAPK pathway reduced viral replication and interferon response. All together, these results contribute to an increased understanding of the innate immune response to H3N2 SIV and may help identify strategies to effectively control SIV infection. PMID:24712747

  9. Porcine circovirus type 2 induces type I interferon production via MyD88-IKKα-IRFs signaling rather than NF-κB in porcine alveolar macrophages in vitro.

    PubMed

    Chen, Mengmeng; Han, Junyuan; Zhang, Yaqun; Duan, Dianning; Zhang, Shuxia

    2016-02-01

    Type I interferon (IFN-I) plays important roles in host antiviral responses. The interferon regulatory factor (IRF) and NF-κB transcription factors are thought to be important in the processes of viral secretion and triggering of interferon production. Recently, studies have shown that porcine circovirus type 2 (PCV2) can induce IFN-I production in vivo and in vitro, but the mechanisms underlying the production of PAMs infected with PCV2 remains unknown. Treatment of these cells with BAY11-7082, an inhibitor of NF-κB activation, allowed us to study the secretion of IFN-α and IFN-β in PAMs infected with PCV2. We found that IFN-α expression was induced following virus infection of PAMs. Notably, even after inhibitor treatment of PAMs infected with PCV2, secretion of IFN-α was significantly higher (P<0.05) compared with the PCV2 infection alone group. Our findings suggest that NF-κB plays a minor role in PCV2-induced type I interferon responses. To further characterize the signaling pathway that drives IFN-I expression in PAMs in response to PCV2, we used siRNA to silence the expression of Myeloid differentiation factor 88 (MyD88) and study the role of MyD88-IKKα-IRF signaling in IFN-I production in PAMs induced by PCV2. Our findings show that PCV2 induced IFN-α mRNA transcription, which is associated with the activities of MyD88, IRF7, and IRF3. Thus, PCV2 can induce IFN-I transcription via the MyD88-IKKα-IRF signaling axis. PMID:26850559

  10. Induction of continuous expanding infrarenal aortic aneurysms in a large porcine animal model

    PubMed Central

    Kloster, Brian O.; Lund, Lars; Lindholt, Jes S.

    2015-01-01

    Background A large animal model with a continuous expanding infrarenal aortic aneurysm gives access to a more realistic AAA model with anatomy and physiology similar to humans, and thus allows for new experimental research in the natural history and treatment options of the disease. Methods 10 pigs (group A) underwent infrarenal aortic dissection, balloon dilatation, infusion of elastase into the lumen and placement of a stenosing cuff around the aorta. 10 control pigs (group B) underwent a sham procedure. The subsequent 28 days the AP-diameters of the aneurysms were measured using ultrasound, hereafter the pigs were euthanized for inspection and AAA wall sampling for histological analysis. Results In group A, all pigs developed continuous expanding AAA's with a mean increase in AP-diameter to 16.26 ± 0.93 mm equivalent to a 57% increase. In group B the AP-diameters increased to 11.33 ± 0.13 mm equivalent to 9.3% which was significantly less than in group A (p < 0.001). In group A, a significant negative association between the preoperative weight and the resulting AP-diameters was found. Histology shoved more or less complete resolution of the elastic tissue in the tunica media in group A. The most frequent complication was a neurological deficit in the lower limbs. Conclusion In pigs it's possible to induce continuous expanding AAA's based upon proteolytic degradation and pathological flow, resembling the real life dynamics of human aneurysms. Because the lumbars are preserved, it's also a potential model for further studies of novel endovascular devices and their complications. PMID:25685342

  11. Porcine gonadogenesis

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Five images submitted for teaching purposes related to porcine gonadogenesis (2), porcine fetal testicular development (2), and porcine fetal ovarian development. Key words include: Egg cell nests, Embryo, GATA4, Genital ridge, Gonad, Leydig cell, Mesonephros, MIS, Ovary, P450c17, Porcine, Sertoli ...

  12. Automated continuous quantitative measurement of proximal airways on dynamic ventilation CT: initial experience using an ex vivo porcine lung phantom

    PubMed Central

    Yamashiro, Tsuneo; Tsubakimoto, Maho; Nagatani, Yukihiro; Moriya, Hiroshi; Sakuma, Kotaro; Tsukagoshi, Shinsuke; Inokawa, Hiroyasu; Kimoto, Tatsuya; Teramoto, Ryuichi; Murayama, Sadayuki

    2015-01-01

    Background The purpose of this study was to evaluate the feasibility of continuous quantitative measurement of the proximal airways, using dynamic ventilation computed tomography (CT) and our research software. Methods A porcine lung that was removed during meat processing was ventilated inside a chest phantom by a negative pressure cylinder (eight times per minute). This chest phantom with imitated respiratory movement was scanned by a 320-row area-detector CT scanner for approximately 9 seconds as dynamic ventilatory scanning. Obtained volume data were reconstructed every 0.35 seconds (total 8.4 seconds with 24 frames) as three-dimensional images and stored in our research software. The software automatically traced a designated airway point in all frames and measured the cross-sectional luminal area and wall area percent (WA%). The cross-sectional luminal area and WA% of the trachea and right main bronchus (RMB) were measured for this study. Two radiologists evaluated the traceability of all measurable airway points of the trachea and RMB using a three-point scale. Results It was judged that the software satisfactorily traced airway points throughout the dynamic ventilation CT (mean score, 2.64 at the trachea and 2.84 at the RMB). From the maximum inspiratory frame to the maximum expiratory frame, the cross-sectional luminal area of the trachea decreased 17.7% and that of the RMB 29.0%, whereas the WA% of the trachea increased 6.6% and that of the RMB 11.1%. Conclusion It is feasible to measure airway dimensions automatically at designated points on dynamic ventilation CT using research software. This technique can be applied to various airway and obstructive diseases. PMID:26445535

  13. Transfer of tylosin resistance between Enterococcus spp. during continuous-flow culture of feral or domestic porcine gut microbes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Mixed populations of domesticated and feral pig gut microbes (RPCF and FC, respectively) were grown in continuous culture to investigate the effects of tylosin on antimicrobial resistance. Cultures established in steady state were inoculated with 9.7 log10 colony forming units (CFU) of a tylosin-re...

  14. Production of porcine TNFα by ADAM17-mediated cleavage negatively regulates porcine reproductive and respiratory syndrome virus infection.

    PubMed

    Li, Ren; Guo, Longjun; Gu, Weihong; Luo, Xiaolei; Zhang, Jian; Xu, Yunfei; Tian, Zhijun; Feng, Li; Wang, Yue

    2016-06-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) causes a series of inflammatory reactions in sites of infection, companied by the upregulation of key inflammatory factor TNFα. TNFα, which serves as a "master regulator" of inflammatory cytokine production, is mainly produced by macrophages at the early infection stage. Here, we showed that porcine alveolar macrophages produced a great amount of soluble TNFα upon PRRSV infection. Furthermore, we found that TNFα had great anti-PRRSV effect. Next, by using inhibitor and genetic modification methods, we addressed that porcine TNFα production was mediated by ADAM17. Lastly, we proved that the (78)Arg-Ser-Ser motif of porcine TNFα contained the essential information for efficient cleavage. Taken together, our findings provide the direct evidence that ADAM17 cleaves porcine TNFα, which represents a new view for identifying potential therapeutic targets in anti-PRRSV therapy. PMID:26724939

  15. Porcine Sialoadhesin: A Newly Identified Xenogeneic Innate Immune Receptor

    PubMed Central

    Brock, Linda G.; Delputte, Peter L.; Waldman, Joshua P.; Nauwynck, Hans J.; Rees, Michael A.

    2012-01-01

    Extracorporeal porcine liver perfusion is being developed as a bridge to liver allotransplantation for patients with fulminant hepatic failure. This strategy is limited by porcine Kupffer cell destruction of human erythrocytes, mediated by lectin binding of a sialic acid motif in the absence of antibody and complement. Sialoadhesin, a macrophage restricted lectin that binds sialic acid, was originally described as a sheep erythrocyte binding receptor. Given similarities between sialoadhesin and the unidentified macrophage lectin in our model, we hypothesized porcine sialoadhesin contributed to recognition of human erythrocytes. Two additional types of macrophages were identified to bind human erythrocytes - spleen and alveolar. Expression of sialoadhesin was confirmed by immunofluorescence in porcine tissues and by flow cytometry on primary macrophages. A stable transgenic cell line expressing porcine sialoadhesin (pSn CHO) bound human erythrocytes, while a sialoadhesin mutant cell line did not. Porcine macrophage and pSn CHO recognition of human erythrocytes was inhibited approximately 90% by an anti-porcine sialoadhesin monoclonal antibody and by human erythrocyte glycoproteins. Furthermore, this binding was substantially reduced by sialidase treatment of erythrocytes. These data support the hypothesis that porcine sialoadhesin is a xenogeneic receptor that mediates porcine macrophage binding of human erythrocytes in a sialic acid-dependent manner. PMID:22958948

  16. 7 CFR 1230.18 - Porcine animal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Porcine animal. 1230.18 Section 1230.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... animal. Porcine animal means a swine, that is raised as (a) a feeder pig, that is, a young pig sold...

  17. 7 CFR 1230.18 - Porcine animal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Porcine animal. 1230.18 Section 1230.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... animal. Porcine animal means a swine, that is raised as (a) a feeder pig, that is, a young pig sold...

  18. 7 CFR 1230.18 - Porcine animal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Porcine animal. 1230.18 Section 1230.18 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS... animal. Porcine animal means a swine, that is raised as (a) a feeder pig, that is, a young pig sold...

  19. In Depth Global Analysis of Transcript Abundance Levels Following Infection with Porcine Reproductive and Respiratory Syndrome Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) is a major pathogen of swine worldwide and causes considerable economic loss. Infection of the primary target cells, porcine alveolar macrophages (PAMs), by PRRSV causes significant changes in their function by mechanisms that are not under...

  20. Marked differences between MARC-145 cells and swine alveolar macrophages in IFN beta-induced activation of antiviral state against PRRSV

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The replication kinetics of field isolates and a vaccine virus of porcine reproductive and respiratory syndrome virus (PRRSV) were evaluated in MARC-145 cells and porcine alveolar macrophages (PAM). In MARC-145 cells, the eclipse period of the vaccine virus was about 10 hours and was shorter than t...

  1. Integrated miRNA and mRNA transcriptomes of porcine alveolar macrophages (PAM cells) identifies strain-specific miRNA molecular signatures associated with H-PRRSV and N-PRRSV infection.

    PubMed

    Cong, Peiqing; Xiao, Shuqi; Chen, Yaosheng; Wang, Liangliang; Gao, Jintao; Li, Ming; He, Zuyong; Guo, Yunxue; Zhao, Guangyin; Zhang, Xiaoyu; Chen, Luxi; Mo, Delin; Liu, Xiaohong

    2014-09-01

    Porcine reproductive and respiratory syndrome (PRRS) is one of the most significant viral diseases in swine, which causes large economic losses to the swine industry worldwide. There is considerable strain variation in PRRSV and two examples of this are the highly virulent Chinese-type PRRSV (H-PRRSV) and the classical North American type PRRSV (N-PRRSV), both with different pathogenesis. These differences may be due in part to genetic and phenotypic differences in virus replication, but also interaction with the host cell. MicroRNAs (miRNAs) are crucial regulators of gene expression and play vital roles in virus and host interactions. However, the regulation role of miRNAs during PRRSV infection has not been systematically investigated. In order to better understand the differential regulation roles of cellular miRNAs in the host response to PRRSV, miRNA expression and a global mRNA transcriptome profile was determined in primary cells infected with either H-PRRSV or N-PRRSV as multiple time points during the viral lifecycle. miRNA-mRNA interactome networks were constructed by integrating the differentially expressed miRNAs and inversely correlated target mRNAs. Using gene ontology and pathway enrichment analyses, cellular pathways associated with deregulated miRNAs were identified, including immune response, phagosome, autophagy, lysosome, autolysis, apoptosis and cell cycle regulation. To our knowledge, this is the first global analysis of strain-specific host miRNA molecular signatures associated with H- and N-PRRSV infection by integrating miRNA and mRNA transcriptomes and provides a new perspective on the contribution of miRNAs to the pathogenesis of PRRSV infection. PMID:24962047

  2. Pulmonary alveolar proteinosis.

    PubMed

    Borie, R; Danel, C; Debray, M-P; Taille, C; Dombret, M-C; Aubier, M; Epaud, R; Crestani, B

    2011-06-01

    Pulmonary alveolar proteinosis (PAP) is a rare pulmonary disease characterised by alveolar accumulation of surfactant. It may result from mutations in surfactant proteins or granulocyte macrophage-colony stimulating factor (GM-CSF) receptor genes, it may be secondary to toxic inhalation or haematological disorders, or it may be auto-immune, with anti-GM-CSF antibodies blocking activation of alveolar macrophages. Auto-immune alveolar proteinosis is the most frequent form of PAP, representing 90% of cases. Although not specific, high-resolution computed tomography shows a characteristic "crazy paving" pattern. In most cases, bronchoalveolar lavage findings establish the diagnosis. Whole lung lavage is the most effective therapy, especially for auto-immune disease. Novel therapies targeting alveolar macrophages (recombinant GM-CSF therapy) or anti-GM-CSF antibodies (rituximab and plasmapheresis) are being investigated. Our knowledge of the pathophysiology of PAP has improved in the past 20 yrs, but therapy for PAP still needs improvement. PMID:21632797

  3. Molecular characterization of porcine SARM1 and its role in regulating TLRs signaling during highly pathogenic porcine reproductive and respiratory syndrome virus infection in vivo.

    PubMed

    Zhou, Xiang; Jiang, Tengfei; Du, Xiaochuan; Zhou, Ping; Jiang, Zhihua; Michal, Jennifer J; Liu, Bang

    2013-01-01

    Toll-like receptors (TLRs) are important pattern-recognition receptors (PRRs) that trigger innate immune response and mediate acquired immunity. Evidence has shown that SARM1 (sterile-α and TIR motif containing protein 1) is one of five TIR domain-containing adaptor proteins involved in TLRs signaling transduction. In the present study, a full-length cDNA sequence was cloned for the porcine SARM1 gene, which contains nine exons. Using the radiation hybrid mapping approach, we assigned the porcine gene to SSC12 q13. Under the normal condition, porcine SARM1 was highly expressed in brain and spleen. Polyinosinic-polycytidylic acid (poly (I:C)) weakly induced the porcine SARM1 expression in the early stimulation. We found that porcine SARM1 protein is localized in mitochondria and attenuates NF-κB activation induced by stimulation and infection. The quantitative real-time PCR (Q-PCR) analysis showed that the expression of porcine SARM1 significantly decreased in several tissues of Tongcheng pigs infected with highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). Gene-interaction network analysis for porcine SARM1 in porcine alveolar macrophages (PAMs) showed that down-regulation of SARM1 gene in infected Tongcheng pig may modulate TRIF-depend TLRs signaling and regulate the expression of disease-resistant genes and inflammatory genes. Our findings provide evidence that porcine SARM1 may play an important role in immune regulation with PRRSV infection. PMID:22366489

  4. [Pulmonary alveolar proteinosis].

    PubMed

    Floarea-Strat, Alina; Stanciu, Adriana; Creţeanu, Mihai

    2003-01-01

    It is a disease of obscure cause that is characterized by the accumulation of a granular material that contains abundant lipid within the alveoli of lung. Pulmonary alveolar proteinosis (PAP) has been divided into a congenital and an adult form. The acquired form has been subdivided into a idiopathic form and a secondary form associated with a know disorder or exposure as silica, aluminium, titanium. Dyspnea and cough are the most common presenting symptoms. Chest pain, hemoptysis, fever and weight loss are variably reported. Pathogenesis remains unknown, but evidence points to a dysfunction of alveolar macrophages. Mice genetically deficient in granulocyte macrophagecolony stimulating factor (GM-CSF) show an alveolar proteinosis. A neutralizing antibody against GM-CSF was found in bronchoalveolar lavage fluid and serum of patients with idiopathic PAP. Currently, no specific therapy exists for pulmonary alveolar proteinosis, and sequential whole lung lavage is standard treatment. PMID:14756054

  5. [Pulmonary alveolar proteinosis].

    PubMed

    Hutyrová, B

    2007-10-01

    Pulmonary alveolar proteinosis is a rare disease characterised by excessive accumulation of surfactant components in the alveoli and the distal airways with minimum inflammatory reaction and fibrosis of pulmonary interstitium. Three clinical forms of pulmonary alveolar proteinosis are distinguished - congenital, primary and secondary. Results of ultrastructural, biochemical and functional analyses and studies performed on genetically modified mice support the presumption that accumulation of surfactant in pulmonary alveolar proteinosis is a result of a degradation disorder and of diminished clearance of the surfactant from the alveolar space rather than of excessive synthesis of surfactant components. Over the last 15 years, significant discoveries have been made which have helped to clarify the etiology and pathogenesis of the disease. A number of gene mutations have been discovered which lead to the development of congenital pulmonary proteinosis. Apart from impaired surfactant protein function, a key role in the development of pulmonary alveolar proteinosis is played by the signal pathway of granulocyte and macrophage colonies stimulating growth factor (GM-CSF) which is necessary for the functioning of alveolar macrophages and for surfactant homeostasis. The role of GM-CSF has been proven especially in primary pulmonary alveolar proteinosis which is currently considered an auto-immune disease involving the development of GM-CSF neutralising autoantibodies. In most cases, the prognosis for the disease in adult patients is good, even though there is a 10 to 15% rate of patients who develop respiratory failure. Total pulmonary lavage is considered to be the standard method of treatment. In recent years, recombinant human GM-CSF has been studied as a prospective therapy for the treatment of pulmonary alveolar proteinosis. PMID:18072433

  6. Review of secondary alveolar cleft repair

    PubMed Central

    Cho-Lee, Gui-Youn; García-Díez, Eloy-Miguel; Nunes, Richard-Agostinho; Martí-Pagès, Carles; Sieira-Gil, Ramón; Rivera-Baró, Alejandro

    2013-01-01

    achieves all these several objectives: (1) to obtain maxillary arch continuity, (2) to maximize bone support for the dentition, (3) to stabilize the maxillary segments after orthodontic treatment, (4) to eliminate oronasal fistulae, (5) to provide nasal alar cartilage support, (6) to establish ideal alveolar morphology, and (7) to provide available bone with attached soft tissue for future endosteal implant placement in cases where there is a residual dental space. We advocate for the use of a minimal incision to obtain the iliac crest bone graft and for the use of a corticocancellous block of bone in combination with bone chips. PMID:23662259

  7. Simple bone augmentation for alveolar ridge defects.

    PubMed

    Haggerty, Christopher J; Vogel, Christopher T; Fisher, G Rawleigh

    2015-05-01

    Dental implant procedures, both surgical placement and preimplant bone augmentation, have become an integral aspect of the oral and maxillofacial surgeon's practice. The number of dental implants placed each year continues to increase as a result of increasing patient exposure and awareness of dental implants, the increased functional and esthetic dental demands of general practitioners and patients, the overall increase in age of the US patient population, and expanded insurance coverage of dental implant-related procedures. This article outlines relevant surgical procedures aimed toward reconstructing alveolar ridge defects to restore intra-arch alveolar discrepancies before restoration-driven dental implant placement. PMID:25951957

  8. Pulmonary alveolar proteinosis.

    PubMed

    Khan, Ajmal; Agarwal, Ritesh

    2011-07-01

    Pulmonary alveolar proteinosis is a rare but potentially treatable disease, characterized by impaired surfactant metabolism that leads to accumulation in the alveoli of proteinaceous material rich in surfactant protein and its component. Novel insights from an animal model aided the discovery of granulocyte macrophage colony stimulating factor (GM-CSF) antibodies as a pathogenetic mechanism in human pulmonary alveolar proteinosis. The vast majority of pulmonary alveolar proteinosis occurs as an autoimmune disease; less commonly, it is congenital or secondary to an underlying disorder such as infection, hematological malignancy, or immunodeficiency. The subacute indolent course of this disease often delays the diagnosis by months to years. Crazy-paving appearance in a geographic distribution is a characteristic feature of this disease visible on high-resolution computed tomography (CT). A definitive diagnosis, however, requires lung biopsy, which typically shows partial or complete filling of alveoli with periodic-acid-Schiff-positive granular and eosinophilic material in preserved alveolar architecture. Patients with minimal symptoms are managed conservatively, whereas patients with hypoxemia require a more aggressive approach. Whole-lung lavage is the most widely accepted therapy for symptomatic pulmonary alveolar proteinosis. Correction of GM-CSF deficiency with exogenous GM-CSF is an alternative therapy. The combination of a systemic treatment (GM-CSF) and a local treatment (whole-lung lavage) augmenting the action of one another is a promising new approach. As the knowledge about this rare disease increases, the role of novel therapies is likely to be better defined and optimized. PMID:21496372

  9. Pulmonary alveolar proteinosis.

    PubMed

    Patel, Sandeep M; Sekiguchi, Hiroshi; Reynolds, Jordan P; Krowka, Michael J

    2012-01-01

    Pulmonary alveolar proteinosis (PAP) is a disease of alveolar accumulation of phospholipoproteinaceous material that results in gas exchange impairment leading to dyspnea and alveolar infiltrates. There are three forms of PAP: congenital, acquired and idiopathic; of which the latter two are predominant in the adult population. Previous case studies have found that the acquired form can be secondary to various autoimmune, infectious, malignant and environmental etiologies. Recent advances in the understanding of the pathophysiology of PAP demonstrate that the idiopathic form is due to antigranulocyte macrophage-colony stimulating factor antibodies. Therapeutic targets that replace granulocyte macrophage colony stimulating factor or remove these antibodies are being actively developed. The current standard of care is to perform whole lung lavage on these patients to clear the alveolar space to help improve respiratory physiology. A case of PAP is reported, followed by a literature review on the diagnosis and management of this rare condition with the aim of increasing awareness among physicians when treating patients who present with alveolar infiltrates. PMID:22891182

  10. Pulmonary alveolar microlithiasis

    PubMed Central

    Kashyap, Surender; Mohapatra, Prasanta R.

    2013-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare, chronic lung disease with bilateral intra-alveolar calcium and phosphate deposition throughout the lung parenchyma with predominance to lower and midzone. Although, etiology and pathogenesis of PAM is not fully understood, the mutation in SLC34A2 gene that encodes a sodium-phosphate co-transporter in alveolar type II cells resulting in the accumulation and forming of microliths rich in calcium phosphate (due to impaired clearance) are considered to be the cause of the disease. Chest radiograph and high-resolution CT of thorax are nearly pathognomonic for diagnosing PAM. HRCT demonstrates diffuse micronodules showing slight perilobular predominance resulting in calcification of interlobular septa. Patients with PAM are asymptomatic till development of hypoxemia and cor-pulmonale. No therapy has been proven to be beneficial except lung transplantation. PMID:23741096

  11. Alveolar wall relations.

    PubMed

    Gil, J

    1982-01-01

    We have presented a highly dynamic view of the alveolar septum and its main enclosed structure, the dense capillary network. The septal or perimicrovascular interstitium is the space between alveolar epithelial sheets after exclusion of the capillary network. It contains cells, fibers, and a viscous matrix. Capillaries form a very complex network, which closely follows the geometry of the terminal airways and participates in functional adaptations of the wall, particularly septal pleating. The level of filling and configuration of different capillaries ranging from collapse to full distension are variable, depending on factors such as transmural balance of forces but also on tissular configuration. Alveolar flooding of any cause will produce an immediate change of capillary configuration and volume. PMID:6953828

  12. Secondary alveolar bone grafting: our experience with olecranon bone graft.

    PubMed

    Nadal, Emmanuela; Sabás, Mariana; Dogliotti, Pedro; Espósito, Raquel

    2010-03-01

    Management of alveolar cleft has dramatically changed during the last century: secondary alveolar bone grafting is now an integral part of cleft palate and craniofacial center's protocols. The objectives of alveolar repair and bone grafting are as follows: providing a continuous and stable maxillary dental arch, closure of oronasal fistulae, adequate bone for tooth eruption or orthodontic movement, and nasal base support, improving facial aesthetic. Although cancellous iliac bone is the donor site selected more frequently, bone grafts harvested from different sites have been advocated to decrease donor site morbidity.The aim of this study was to propose and evaluate the use of olecranon as a donor site in 24 patients with secondary alveolar cleft. The graft is taken as a single piece to fit the alveolar cleft defect, and it includes periosteum and corticocancellous bone to improve early vascularization and greater volume maintenance. PMID:20186086

  13. Inhibition of porcine reproductive and respiratory syndrome virus by Cecropin D in vitro.

    PubMed

    Liu, Xiaohong; Guo, Chunhe; Huang, Yumao; Zhang, Xiaoyu; Chen, Yaosheng

    2015-08-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) continues to cause substantial economic losses to the pig industry worldwide. Although vaccines are commercially available for the control of PRRSV infection, no vaccination regimen has been proved sustained success in terms of generating a protective immune response. Therefore, the development of novel antivirals is urgently needed. Antimicrobial peptides display broad-spectrum antimicrobial activities against bacteria, fungi, and viruses and play an important role in host innate immune response. Here, we tested whether Cecropin D (CD) could inhibit PRRSV infection and replication in vitro. The inhibitory effect of CD occurred during viral attachment and the early period of viral entry into Marc-145 cells. CD also attenuated virus-induced apoptosis during the late phase of PRRSV infection and suppressed virus release in Marc-145 cells, which might contribute to the inhibition of PRRSV infection. Similar inhibitory effects on PRRSV infection were also found with CD treatment in porcine alveolar macrophages, the major target cell type of PRRSV infection in pigs in vivo. These findings suggest that CD has the potential to develop a new therapeutic agent against PRRSV infection. PMID:26102162

  14. Porcine TLR3 characterization and expression in response to influenza virus and Bordetella bronchiseptica

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We have provided a detailed structural analysis of porcine alveolar macrophage TLR3 extracellular domain (ECD). The pTLR3-ECD contains 18 leucine-rich repeat (LRRs) consisting of blocks of consensus motifs and non-consensus motifs containing insertions. Excluding the N-terminal and C-terminal LRRs, ...

  15. Differential roles of Toll-like receptors in the elicitation of type I interferon responses by alveolar macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Control of virus replication initially depends on rapid activation of the innate immune responses. Toll-like receptor (TLR) ligands are potent inducers of innate immunity against viral infections. Porcine reproductive and respiratory syndrome virus (PRRSV) initiates infection in pulmonary alveolar...

  16. Antibody repertoire development in fetal and neonatal piglets. XV. Porcine circovirus type 2 infection differentially affects serum IgG levels and antibodies to ORF2 in piglets free from other environmental factors

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine circovirus type 2 (PCV2) is an important pathogen in the porcine respiratory disease complex (PRDC) and its persistence may be due to dysregulation of systemic immunity. We examined this contention using isolator piglets. We present data on Ig levels in serum and bronchio-alveolar lavage (BA...

  17. Pulmonary alveolar proteinosis.

    PubMed

    Wang, Tisha; Lazar, Catherine A; Fishbein, Michael C; Lynch, Joseph P

    2012-10-01

    Pulmonary alveolar proteinosis (PAP) is a rare disorder characterized by the accumulation of surfactant lipids and protein in the alveolar spaces, with resultant impairment in gas exchange. The clinical course can be variable, ranging from spontaneous resolution to respiratory failure and death. PAP in all forms is caused by excessive accumulation of surfactant within the alveolar spaces. Autoimmune PAP accounts for the vast majority of cases in humans and is caused by autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF), which results in impaired catabolism and clearance of surfactant lipids and proteins. Inherited or congenital forms of PAP are exceptionally rare and caused by mutations of genes encoding for surfactant proteins. Secondary forms of PAP are associated with diverse clinical disorders and are caused by reduced alveolar macrophage numbers or function with resultant reduced pulmonary clearance of surfactant. PAP is characterized by progressive exertional dyspnea and nonproductive cough with hypoxemia. Bilateral infiltrates are typically present on chest radiograph, and high-resolution computed tomography reveals diffuse ground-glass opacities and airspace consolidation with interlobular septal thickening in a characteristic "crazy paving" pattern. Although surgical lung biopsy will provide a definitive diagnosis, a combination of typical clinical and imaging features with periodic acid-Schiff (PAS)-positive material on bronchoalveolar lavage and transbronchial biopsies is usually sufficient. The standard of care for treatment of PAP remains whole lung lavage, but treatment is not required in all patients. Autoimmune PAP has also been successfully treated with GM-CSF, both inhaled and systemic, but the optimal dose, duration, and route of administration of GM-CSF have not been elucidated. PMID:23001804

  18. Alveolar development and disease.

    PubMed

    Whitsett, Jeffrey A; Weaver, Timothy E

    2015-07-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis. PMID:25932959

  19. Alveolar Development and Disease

    PubMed Central

    Weaver, Timothy E.

    2015-01-01

    Gas exchange after birth is entirely dependent on the remarkable architecture of the alveolus, its formation and function being mediated by the interactions of numerous cell types whose precise positions and activities are controlled by a diversity of signaling and transcriptional networks. In the later stages of gestation, alveolar epithelial cells lining the peripheral lung saccules produce increasing amounts of surfactant lipids and proteins that are secreted into the airspaces at birth. The lack of lung maturation and the associated lack of pulmonary surfactant in preterm infants causes respiratory distress syndrome, a common cause of morbidity and mortality associated with premature birth. At the time of birth, surfactant homeostasis begins to be established by balanced processes involved in surfactant production, storage, secretion, recycling, and catabolism. Insights from physiology and engineering made in the 20th century enabled survival of newborn infants requiring mechanical ventilation for the first time. Thereafter, advances in biochemistry, biophysics, and molecular biology led to an understanding of the pulmonary surfactant system that made possible exogenous surfactant replacement for the treatment of preterm infants. Identification of surfactant proteins, cloning of the genes encoding them, and elucidation of their roles in the regulation of surfactant synthesis, structure, and function have provided increasing understanding of alveolar homeostasis in health and disease. This Perspective seeks to consider developmental aspects of the pulmonary surfactant system and its importance in the pathogenesis of acute and chronic lung diseases related to alveolar homeostasis. PMID:25932959

  20. A comparative study on the effect of subtherapeutic tylosin administration on select feral or domestic porcine gut microflora grown in continuous-flow culture

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Continuous flow cultures of feral (culture FC) and domesticated (culture RPCF) pig gut microflora were established in steady state. Cultures, in duplicate, were continuously infused subtherapeutic (25 ug/ml) levels of tylosin and sampled at intervals to assess effects on total culturable anaerobes,...

  1. Novel porcine repetitive elements

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An analysis of 220 fully sequenced porcine BACs generated by the Comparative Vertebrate Sequencing Initiative (http://www.nisc.nih.gov/) revealed 27 distinct, novel porcine repetitive elements ranging in length from 55 to 1059 nucleotides. This set of fully sequenced BACs covers approximately 1% of...

  2. Pulmonary alveolar proteinosis.

    PubMed

    Ioachimescu, O C; Kavuru, M S

    2006-01-01

    Pulmonary alveolar proteinosis is a rare syndrome characterized by intra-alveolar accumulation of surfactant components and cellular debris, with minimal interstitial inflammation or fibrosis. The condition has a variable clinical course, from spontaneous resolution to respiratory failure and death due to disease progression or superimposed infections. The standard of care for alveolor proteinosis therapy is represented by whole lung lavage. Important discoveries have been made in the last decade with respect to disease pathogenesis and therapy of both congenital and acquired forms of the disease. Granulocyte-macrophage colony-stimulating factor (GM-CSF) pathway has been shown to be involved in the disease pathogenesis of both acquired and congenital disease. Furthermore, anti-GM-CSF blocking autoantibodies have been found in the serum and bronchoalveolar lavage fluid and seem to interfere with the surfactant clearance by alveolar macrophages in many acquired cases. In the congenital form, the most common defects identified to date are several mutations of the genes encoding GM-CSF receptor subunits or surfactant proteins. Using GM-CSF as a therapeutic tool has also been shown to be effective in at least half of the acquired cases treated, while the importance of quantitative determination of anti-GM-CSF antibodies before and during the course of the therapy, as well as the autoantibody titer-GM-CSF dose relationship are to be elucidated. The congenital form of the disease does not respond to therapy with GM-CSF, consistent with the known primary defects and differences in disease pathogenesis. PMID:16916009

  3. Pulmonary Alveolar Proteinosis Syndrome.

    PubMed

    Suzuki, Takuji; Trapnell, Bruce C

    2016-09-01

    Pulmonary alveolar proteinosis (PAP) is a rare syndrome characterized by the accumulation of surfactant in alveoli and terminal airways resulting in respiratory failure. PAP comprises part of a spectrum of disorders of surfactant homeostasis (clearance and production). The surfactant production disorders are caused by mutations in genes required for normal surfactant production. The PAP syndrome is identified based on history, radiologic, and bronchoalveolar lavage and/or histopathologic findings. The diagnosis of PAP-causing diseases in secondary PAP requires further studies. Whole-lung lavage is the current standard therapy and promising new pharmacologic therapies are in development. PMID:27514590

  4. Pulmonary Alveolar Microlithiasis

    PubMed Central

    Mehta, Kevan; Dell, Sharon; Birken, Catherine; Al-Saleh, Suhail

    2016-01-01

    Pulmonary alveolar microlithiasis (PAM) is a rare autosomal recessive condition that is often asymptomatic despite significant changes in chest imaging. Diagnosis is often made when patients become symptomatic in adulthood. There are still no proven treatments, but earlier diagnosis may allow for evaluation of preventative strategies that could improve outcome. It is an important diagnosis to consider in children who have marked radiographic findings with no or very mild symptoms or physical findings. Diagnosis can be made with imaging alone but may necessitate lung biopsy for definitive diagnosis. PMID:27445543

  5. Alveolar Capillary Dysplasia

    PubMed Central

    Stankiewicz, Pawel; Steinhorn, Robin H.

    2011-01-01

    Alveolar capillary dysplasia with misalignment of the pulmonary veins (ACD/MPV) is a rare, fatal developmental lung disorder of neonates and infants. This review aims to address recent findings in the etiology and genetics of ACD/MPV and to raise awareness of this poorly known disease, which may also present as milder, unclassified forms. Successively discussed are what is known about the epidemiology, pathogenesis, pathophysiology, diagnostic indicators and approaches, genetic testing, treatment, and cases of delayed onset. The review concludes with suggestions for future directions to answer the many unknowns about this disorder. PMID:21471096

  6. Alveolar rhabdomyosarcoma of maxilla

    PubMed Central

    Ananthaneni, Anuradha; Kuberappa, Puneeth Horatti; Srinivas, G Vijay; Kiresur, Mohammad Asif

    2016-01-01

    Rhabdomyosarcoma (RMS), a malignant neoplasm of skeletal muscle origin, is the most common soft tissue sarcoma seen in childhood and adolescence. The most frequent site is the head and neck accounting for 40% of all cases and other involved sites are genitourinary tract, retroperitoneum, and to a lesser extent, the extremities. RMS is relatively uncommon in the oral cavity and the involvement of the jaws is extremely rare. Here, we report a case of 50-year-old female with oral RMS involving maxillary alveolar region with clinical, radiological, histopathological and immunohistochemical findings. PMID:27194887

  7. Alveolar rhabdomyosarcoma of maxilla.

    PubMed

    Ananthaneni, Anuradha; Kuberappa, Puneeth Horatti; Srinivas, G Vijay; Kiresur, Mohammad Asif

    2016-01-01

    Rhabdomyosarcoma (RMS), a malignant neoplasm of skeletal muscle origin, is the most common soft tissue sarcoma seen in childhood and adolescence. The most frequent site is the head and neck accounting for 40% of all cases and other involved sites are genitourinary tract, retroperitoneum, and to a lesser extent, the extremities. RMS is relatively uncommon in the oral cavity and the involvement of the jaws is extremely rare. Here, we report a case of 50-year-old female with oral RMS involving maxillary alveolar region with clinical, radiological, histopathological and immunohistochemical findings. PMID:27194887

  8. Gene Expression Profiling of Porcine Reproductive and Respiratory Syndrome Virus Infected Porcine Alveolar Macrophages

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Identifying specific pathways that associate with variation in PRRSV replication and macrophage function can lead to novel gene targets for the control of PRRSV infection. Serial Analysis of Gene Expression (SAGE) is a powerful technique that allows a detailed and profound quantitative and qualitati...

  9. Immunohistochemistry of porcine skin.

    PubMed

    Wollina, U; Berger, U; Mahrle, G

    1991-01-01

    The present paper reports immunohistological findings in porcine skin, which were obtained by use of mono- and polyclonal antihuman antibodies and either alkaline phosphatase anti-alkaline phosphatase (APAAP) or peroxidase (POX) technique. Epidermal staining was observed with antibodies to keratins (K 8.12, RSKE 60), filaggrin, and calmodulin (ACAM). Staining of connective tissue and vessels was achieved using antibodies to vimentin (V9(1)), collagen type IV, and fibronectin. In general, these antibodies gave a staining pattern similar to that of normal human skin. The similarities of immunoreactivity to poly- and monoclonal antihuman antibodies in porcine and human skin render porcine skin a reliable model in biomedical research. PMID:1710864

  10. Alveolar bone grafting

    PubMed Central

    Lilja, Jan

    2009-01-01

    In patients with cleft lip and palate, bone grafting in the mixed dentition in the residual alveolar cleft has become a well-established procedure. The main advantages can be summarised as follows: stabilisation of the maxillary arch; facilitation of eruption of the canine and sometimes facilitation of the lateral incisor eruption; providing bony support to the teeth adjacent to the cleft; raising the alar base of the nose; facilitation of closure of an oro-nasal fistula; making it possible to insert a titanium fixture in the grafted site and to obtain favourable periodontal conditions of the teeth within and adjacent to the cleft. The timing of the ABG surgery take into consideration not only eruption of the canine but also that of the lateral incisor, if present. The best time for bone grafting surgery is when a thin shell of bone still covers the soon erupting lateral incisor or canine tooth close to the cleft. PMID:19884665

  11. Porcine skin damage thresholds for 0.6 to 9.5 cm beam diameters from 1070-nm continuous-wave infrared laser radiation.

    PubMed

    Vincelette, Rebecca; Noojin, Gary D; Harbert, Corey A; Schuster, Kurt J; Shingledecker, Aurora D; Stolarski, Dave; Kumru, Semih S; Oliver, Jeffrey W

    2014-03-01

    There is an increasing use of high-power fiber lasers in manufacturing and telecommunications industries operating in the infrared spectrum between 1000 and 2000 nm, which are advertised to provide as much as 10 kW continuous output power at 1070 nm. Safety standards have traditionally been based on experimental and modeling investigations with scant data available for these wavelengths. A series of studies using 1070-nm infrared lasers to determine the minimum visible lesion damage thresholds in skin using the Yucatan miniature pig (Sus scrofa domestica) for a range of beam diameters (0.6, 1.1, 1.9, 2.4, 4.7, and 9.5 cm) and a range of exposure durations (10 ms to 10 s) is presented. Experimental peak temperatures associated with each damage threshold were measured using thermal imaging. Peak temperatures at damage threshold for the 10-s exposures were ∼10°C lower than those at shorter exposures. The lowest and highest experimental minimum visible lesion damage thresholds were found to have peak radiant exposures of 19 and 432  J/cm2 for the beam diameter-exposure duration pairs of 2.4 cm, 25 ms and 0.6 cm, 10 s, respectively. Thresholds for beam diameters >2.5  cm had a weak to no effect on threshold radiant exposure levels for exposure times ≤0.25  s, but may have a larger effect on thresholds for exposures ≥10  s. PMID:24658776

  12. Blood gas and hematological changes in experimental peracute porcine pleuropneumonia.

    PubMed Central

    Kiorpes, A L; MacWilliams, P S; Schenkman, D I; Bäckström, L R

    1990-01-01

    The effect of experimental, peracute, porcine pleuropneumonia on arterial blood gases, acid base status, the leukogram, and gross and microscopic lung structure was studied in nine growing pigs (mean weight +/- SD 10.6 +/- 2.0 kg). Pigs were inoculated intranasally with a virulent serotype 5 isolate of Actinobacillus pleuropneumoniae, and all showed signs typical of the disease within four hours. Death occurred in all pigs from 4.5 to 32 hours postinoculation (mean 14 hours). Gross and microscopic changes were typical of porcine pleuropneumonia in all pigs. Changes in the leukogram included a rapid decline in total white cells, segmented neutrophils, lymphocytes, monocytes, and eosinophils. Pigs maintained alveolar ventilation throughout the study as arterial CO2 tension was unchanged; however, arterial O2 tension and pH decreased from (mean +/- SD) 95.2 +/- 5.7 torr and 7.463 +/- 0.018 at baseline to 62.1 +/- 12.3 torr and 7.388 +/- 0.045, respectively, within 90 minutes prior to death. The data showed that in this model of peracute porcine pleuropneumonia, progressive ventilatory failure was not a feature of the disease, and the blood gas values and acid base status were maintained within physiological ranges. The histopathological hematological and physiological findings were consistent with the hypothesis that peracute porcine pleuropneumonia resembles septic shock. Images Fig. 2. Fig. 3. PMID:2106382

  13. PPARs in alveolar macrophage biology.

    PubMed

    Smith, Monica R; Standiford, Theodore J; Reddy, Raju C

    2007-01-01

    PPARs, most notably PPAR-gamma, play a crucial role in regulating the activation of alveolar macrophages, which in turn occupy a pivotal place in the immune response to pathogens and particulates drawn in with inspired air. In this review, we describe the dual role of the alveolar macrophage as both a first-line defender through its phagocytotic activity and a regulator of the immune response. Depending on its state of activation, the alveolar macrophage may either enhance or suppress different aspects of immune function in the lung. We then review the role of PPAR-gamma and its ligands in deactivating alveolar macrophages-thus limiting the inflammatory response that, if unchecked, could threaten the essential respiratory function of the alveolus-while upregulating the cell's phagocytotic activity. Finally, we examine the role that inadequate or inappropriate PPAR-gamma responses play in specific lung diseases. PMID:18000531

  14. Micronuclei in human alveolar macrophages.

    PubMed

    D'Agostini, F; Bonatti, S; Oddera, S; De Flora, S

    1992-01-01

    Occurrence of micronuclei was monitored in pulmonary alveolar macrophages collected from 31 individuals undergoing diagnostic bronchoalveolar lavage. The overall frequency of micronucleated cells was 3.88 +/- 1.84/1000, without any significant difference attributable to sex, age, pathology, occupation, or smoking habits. The lack of influence of cigarette smoke on this clastogenicity index presumably reflects the very low rate of mitoses of macrophages in the alveolar lumen. PMID:1579732

  15. Inferior alveolar nerve repositioning.

    PubMed

    Louis, P J

    2001-09-01

    Nerve repositioning is a viable alternative for patients with an atrophic edentulous posterior mandible. Patients, however, should be informed of the potential risks of neurosensory disturbance. Documentation of the patient's baseline neurosensory function should be performed with a two-point discrimination test or directional brush stroke test preoperatively and postoperatively. Recovery of nerve function should be expected in 3 to 6 months. The potential for mandibular fracture when combining nerve repositioning with implant placement also should be discussed with the patient. This can be avoided by minimizing the amount of buccal cortical plate removal during localization of the nerve and maintaining the integrity of the inferior cortex of the mandible. Additionally, avoid overseating the implant, thus avoiding stress along the inferior border of the mandible. The procedure does allow for the placement of longer implants, which should improve implant longevity. Patients undergoing this procedure have expressed overall satisfaction with the results. Nerve repositioning also can be used to preserve the inferior alveolar nerve during resection of benign tumors or cysts of the mandible. This procedure allows the surgeon to maintain nerve function in situations in which the nerve would otherwise have to be resected. PMID:11665379

  16. Micromechanics of alveolar edema.

    PubMed

    Perlman, Carrie E; Lederer, David J; Bhattacharya, Jahar

    2011-01-01

    The decrease of lung compliance in pulmonary edema underlies ventilator-induced lung injury. However, the cause of the decrease in compliance is unknown. We tested the hypothesis that in pulmonary edema, the mechanical effects of liquid-filled alveoli increase tissue stress in adjacent air-filled alveoli. By micropuncture of isolated, perfused rat lungs, we established a single-alveolus model of pulmonary edema that we imaged using confocal microscopy. In this model, we viewed a liquid-filled alveolus together with its air-filled neighbor at different transpulmonary pressures, both before and after liquid-filling. Instilling liquid in an alveolus caused alveolar shrinkage. As a result, the interalveolar septum was stretched, causing the neighboring air-filled alveolus to bulge. Thus, the air-filled alveolus was overexpanded by virtue of its adjacency to a liquid-filled alveolus. Confocal microscopy at different depths of the liquid-filled alveolus revealed a meniscus. Lung inflation to near-total lung capacity (TLC) demonstrated decreased compliance of the air-filled but not liquid-filled alveolus. However, at near TLC, the air-filled alveolus was larger than it was in the pre-edematous control tissue. In pulmonary edema, liquid-filled alveoli induce mechanical stress on air-filled alveoli, reducing the compliance of air-filled alveoli, and hence overall lung compliance. Because of increased mechanical stress, air-filled alveoli may be susceptible to overdistension injury during mechanical ventilation of the edematous lung. PMID:20118224

  17. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity.

    PubMed

    Westphalen, Kristin; Gusarova, Galina A; Islam, Mohammad N; Subramanian, Manikandan; Cohen, Taylor S; Prince, Alice S; Bhattacharya, Jahar

    2014-02-27

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca(2+) waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca(2+)-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation. PMID:24463523

  18. Sessile alveolar macrophages communicate with alveolar epithelium to modulate immunity

    NASA Astrophysics Data System (ADS)

    Westphalen, Kristin; Gusarova, Galina A.; Islam, Mohammad N.; Subramanian, Manikandan; Cohen, Taylor S.; Prince, Alice S.; Bhattacharya, Jahar

    2014-02-01

    The tissue-resident macrophages of barrier organs constitute the first line of defence against pathogens at the systemic interface with the ambient environment. In the lung, resident alveolar macrophages (AMs) provide a sentinel function against inhaled pathogens. Bacterial constituents ligate Toll-like receptors (TLRs) on AMs, causing AMs to secrete proinflammatory cytokines that activate alveolar epithelial receptors, leading to recruitment of neutrophils that engulf pathogens. Because the AM-induced response could itself cause tissue injury, it is unclear how AMs modulate the response to prevent injury. Here, using real-time alveolar imaging in situ, we show that a subset of AMs attached to the alveolar wall form connexin 43 (Cx43)-containing gap junction channels with the epithelium. During lipopolysaccharide-induced inflammation, the AMs remained sessile and attached to the alveoli, and they established intercommunication through synchronized Ca2+ waves, using the epithelium as the conducting pathway. The intercommunication was immunosuppressive, involving Ca2+-dependent activation of Akt, because AM-specific knockout of Cx43 enhanced alveolar neutrophil recruitment and secretion of proinflammatory cytokines in the bronchoalveolar lavage. A picture emerges of a novel immunomodulatory process in which a subset of alveolus-attached AMs intercommunicates immunosuppressive signals to reduce endotoxin-induced lung inflammation.

  19. Hereditary Pulmonary Alveolar Proteinosis

    PubMed Central

    Suzuki, Takuji; Sakagami, Takuro; Young, Lisa R.; Carey, Brenna C.; Wood, Robert E.; Luisetti, Maurizio; Wert, Susan E.; Rubin, Bruce K.; Kevill, Katharine; Chalk, Claudia; Whitsett, Jeffrey A.; Stevens, Carrie; Nogee, Lawrence M.; Campo, Ilaria; Trapnell, Bruce C.

    2010-01-01

    Rationale: We identified a 6-year-old girl with pulmonary alveolar proteinosis (PAP), impaired granulocyte-macrophage colony–stimulating factor (GM-CSF) receptor function, and increased GM-CSF. Objectives: Increased serum GM-CSF may be useful to identify individuals with PAP caused by GM-CSF receptor dysfunction. Methods: We screened 187 patients referred to us for measurement of GM-CSF autoantibodies to diagnose autoimmune PAP. Five were children with PAP and increased serum GM-CSF but without GM-CSF autoantibodies or any disease causing secondary PAP; all were studied with family members, subsequently identified patients, and controls. Measurement and Main Results: Eight children (seven female, one male) were identified with PAP caused by recessive CSF2RA mutations. Six presented with progressive dyspnea of insidious onset at 4.8 ± 1.6 years and two were asymptomatic at ages 5 and 8 years. Radiologic and histopathologic manifestations were similar to those of autoimmune PAP. Molecular analysis demonstrated that GM-CSF signaling was absent in six and severely reduced in two patients. The GM-CSF receptor β chain was detected in all patients, whereas the α chain was absent in six and abnormal in two, paralleling the GM-CSF signaling defects. Genetic analysis revealed multiple distinct CSF2RA abnormalities, including missense, duplication, frameshift, and nonsense mutations; exon and gene deletion; and cryptic alternative splicing. All symptomatic patients responded well to whole-lung lavage therapy. Conclusions: CSF2RA mutations cause a genetic form of PAP presenting as insidious, progressive dyspnea in children that can be diagnosed by a combination of characteristic radiologic findings and blood tests and treated successfully by whole-lung lavage. PMID:20622029

  20. CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia.

    PubMed

    Li, Xiaopeng; Comellas, Alejandro P; Karp, Philip H; Ernst, Sarah E; Moninger, Thomas O; Gansemer, Nicholas D; Taft, Peter J; Pezzulo, Alejandro A; Rector, Michael V; Rossen, Nathan; Stoltz, David A; McCray, Paul B; Welsh, Michael J; Zabner, Joseph

    2012-07-01

    A balance between alveolar liquid absorption and secretion is critical for maintaining optimal alveolar subphase liquid height and facilitating gas exchange in the alveolar space. However, the role of cystic fibrosis transmembrane regulator protein (CFTR) in this homeostatic process has remained elusive. Using a newly developed porcine model of cystic fibrosis, in which CFTR is absent, we investigated ion transport properties and alveolar liquid transport in isolated type II alveolar epithelial cells (T2AECs) cultured at the air-liquid interface. CFTR was distributed exclusively to the apical surface of cultured T2AECs. Alveolar epithelia from CFTR(-/-) pigs failed to increase liquid absorption in response to agents that increase cAMP, whereas cAMP-stimulated liquid absorption in CFTR(+/-) epithelia was similar to that in CFTR(+/+) epithelia. Expression of recombinant CFTR restored stimulated liquid absorption in CFTR(-/-) T2AECs but had no effect on CFTR(+/+) epithelia. In ex vivo studies of nonperfused lungs, stimulated liquid absorption was defective in CFTR(-/-) alveolar epithelia but similar between CFTR(+/+) and CFTR(+/-) epithelia. When epithelia were studied at the air-liquid interface, elevating cAMP levels increased subphase liquid height in CFTR(+/+) but not in CFTR(-/-) T2AECs. Our findings demonstrate that CFTR is required for maximal liquid absorption under cAMP stimulation, but it is not the rate-limiting factor. Furthermore, our data define a role for CFTR in liquid secretion by T2AECs. These insights may help to develop new treatment strategies for pulmonary edema and respiratory distress syndrome, diseases in which lung liquid transport is disrupted. PMID:22637155

  1. CFTR is required for maximal transepithelial liquid transport in pig alveolar epithelia

    PubMed Central

    Li, Xiaopeng; Comellas, Alejandro P.; Karp, Philip H.; Ernst, Sarah E.; Moninger, Thomas O.; Gansemer, Nicholas D.; Taft, Peter J.; Pezzulo, Alejandro A.; Rector, Michael V.; Rossen, Nathan; Stoltz, David A.; McCray, Paul B.; Welsh, Michael J.

    2012-01-01

    A balance between alveolar liquid absorption and secretion is critical for maintaining optimal alveolar subphase liquid height and facilitating gas exchange in the alveolar space. However, the role of cystic fibrosis transmembrane regulator protein (CFTR) in this homeostatic process has remained elusive. Using a newly developed porcine model of cystic fibrosis, in which CFTR is absent, we investigated ion transport properties and alveolar liquid transport in isolated type II alveolar epithelial cells (T2AECs) cultured at the air-liquid interface. CFTR was distributed exclusively to the apical surface of cultured T2AECs. Alveolar epithelia from CFTR−/− pigs failed to increase liquid absorption in response to agents that increase cAMP, whereas cAMP-stimulated liquid absorption in CFTR+/− epithelia was similar to that in CFTR+/+ epithelia. Expression of recombinant CFTR restored stimulated liquid absorption in CFTR−/− T2AECs but had no effect on CFTR+/+ epithelia. In ex vivo studies of nonperfused lungs, stimulated liquid absorption was defective in CFTR−/− alveolar epithelia but similar between CFTR+/+ and CFTR+/− epithelia. When epithelia were studied at the air-liquid interface, elevating cAMP levels increased subphase liquid height in CFTR+/+ but not in CFTR−/− T2AECs. Our findings demonstrate that CFTR is required for maximal liquid absorption under cAMP stimulation, but it is not the rate-limiting factor. Furthermore, our data define a role for CFTR in liquid secretion by T2AECs. These insights may help to develop new treatment strategies for pulmonary edema and respiratory distress syndrome, diseases in which lung liquid transport is disrupted. PMID:22637155

  2. Is alveolar cleft reconstruction still controversial? (Review of literature)

    PubMed Central

    Seifeldin, Sameh A.

    2015-01-01

    Cleft lip and palate (CL/P) is a frequent congenital malformation that manifests in several varieties including unilateral or bilateral and complete or incomplete. Alveolar cleft reconstruction remains controversial with regard to timing, graft materials, surgical techniques, and methods of evaluation. Many studies have been conducted addressing these points to develop an acceptable universal protocol for managing CL/P. The primary goal of alveolar cleft reconstruction in CL/P patients is to provide a bony bridge at the cleft site that allows maxillary arch continuity, oronasal fistula repair, eruption of the permanent dentition into the newly formed bone, enhances nasal symmetry through providing alar base support, orthodontic movement and placement of osseointegrated implants when indicated. Other goals include improving speech, improvement of periodontal conditions, establishing better oral hygiene, and limiting growth disturbances. In order to rehabilitate oral function in CL/P patients alveolar bone grafting is necessary. Secondary bone grafting is the most widely accepted method for treating alveolar clefts. Autogenous bone graft is the primary source for reconstructing alveolar cleft defects and is currently the preferred grafting material. PMID:26792963

  3. Molecular cloning, chromosomal location, and expression analysis of porcine CD14.

    PubMed

    Sanz, Gema; Pérez, Eva; Jiménez-Marín, Angeles; Mompart, Florence; Morera, Luis; Barbancho, Manuel; Llanes, Diego; Garrido, Juan J

    2007-01-01

    CD14 is a membrane-associated glycosylphosphatidylinositol (GPI)-anchored protein that binds lipopolysaccharide (LPS) of Gram-negative bacteria and enables LPS-dependent responses in a variety of cells. In this study a cDNA containing the porcine CD14 coding sequence has been cloned and its complete sequence determined. The amino acid sequence deduced from pig CD14 cDNA encodes a 373 amino acid polypeptide that exhibits 75%, 72%, 69%, 66%, 57% and 56% similarity to CD14 from cow, horse, human, rabbit, mouse and rat, respectively. Structural analysis showed that the porcine CD14 is a membrane glycoprotein with a GPI-anchor site and an extracellular domain containing 11 leucine-rich repeats. In addition, the LPS-binding regions identified in the human CD14 are highly conserved in the N-terminal domain of the porcine sequence. Fluorescence in situ hybridization was used to locate the CD14 gene on the pig chromosome 2, band q28. Expression analysis revealed that porcine CD14 transcripts were detected in all tissues and cells examined, suggesting that the expression of porcine CD14 gene is not restricted to myeloid cell lineage. Finally, we report that LPS stimulation significantly up-regulated CD14 gene expression in porcine alveolar macrophages. PMID:17169425

  4. Use of an Ex Vivo Porcine Mucosal Model to Study Superantigen Penetration.

    PubMed

    Squier, Christopher A; Mantz, Mary J

    2016-01-01

    In vitro perfusion studies are frequently used to determine the penetration of compounds through skin and mucosa. Porcine tissue has been shown to be an excellent model for human tissue in terms of structure, function, and reactivity. We describe the use of porcine tissue ex-vivo in a continuous flow perfusion system to study the behavior of superantigens in this model. PMID:26676044

  5. Human Alveolar Echinococcosis in Kyrgyzstan

    PubMed Central

    Usubalieva, Jumagul; Minbaeva, Gulnara; Ziadinov, Iskender; Deplazes, Peter

    2013-01-01

    Human echinococcosis is a reportable disease in Kyrgyzstan. Between 1995 and 2011, human alveolar echinococcosis increased from <3 cases per year to >60 cases per year. The origins of this epidemic, which started in 2004, may be linked to the socioeconomic changes that followed the dissolution of the former Soviet Union. PMID:23763935

  6. Molecular characterization of the porcine S100A6 gene and analysis of its expression in pigs infected with highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV).

    PubMed

    Zhou, Xiang; Wang, Peng; Michal, Jennifer J; Wang, Yan; Zhao, Jinhua; Jiang, Zhihua; Liu, Bang

    2015-08-01

    Our previous microarray study revealed that S100A6 was significantly upregulated in porcine alveolar macrophages (PAMs) infected with highly pathogenic porcine reproductive and respiratory syndrome virus (HP-PRRSV). In the present study, we cloned both cDNA and genomic DNA sequences of the gene. Transient transfection indicated that the porcine S100A6 protein was located in the nucleus and cytoplasm. Reverse transcription polymerase chain reaction (RT-PCR) revealed that the porcine S100A6 gene was highly expressed in the kidney and subcutaneous fat. Polyinosinic-polycytidylic acid [poly (I:C)] induced porcine S100A6 gene expression in PK-15 cells. Quantitative real-time PCR (Q-PCR) analysis further showed that the porcine S100A6 gene was upregulated in different cells and tissues of Tongcheng pigs infected with HP-PRRSV. Chromosome walking obtained the porcine S100A6 promoter region and then luciferase reporter assays confirmed its regulatory activities. We observed a putative NF-κB binding site in the core promoter region, which may explain the upregulation of porcine S100A6 in response to PRRSV. Transfection of NF-κB (p65 subunit) intensely induced the promoter activity of the porcine S100A6 gene, while an NF-κB inhibitor, pyrrolidine dithiocarbamate (PDTC), inhibited this activity. Furthermore, compared to its wild type, the promoter activity was significantly reduced when it contained a mutant NF-κB binding site. All these results provide a solid foundation to further investigate how S100A6 is involved in PRRSV infection. PMID:25480733

  7. Molecular cloning and characterizations of porcine SAMHD1 and its roles in replication of highly pathogenic porcine reproductive and respiratory syndrome virus.

    PubMed

    Yang, Shen; Shan, Tongling; Zhou, Yanjun; Jiang, Yifeng; Tong, Wu; Liu, Fei; Wen, Feng; Zhang, Qingzhan; Tong, Guangzhi

    2014-12-01

    The sterile alpha motif and HD domain 1 (SAMHD1) protein is a novel innate immunity restriction factor that inhibits HIV-1 infection in myeloid cells. Here, we cloned the full-length SAMHD1 complementary DNA (cDNA) from porcine peripheral blood lymphocytes. The porcine SAMHD1 cDNA was of 3951 bp with an open reading frame of 1884 bp, encoding a polypeptide of 627 amino acids. Porcine SAMHD1 mRNA was detected in all swine tissues examined, with the higher expression in the tonsil, lung, liver, and lymph node tissues. The SAMHD1 protein was localized to the nucleus. Overexpression of SAMHD1 blocked the proliferation of HuN4, a highly pathogenic strain of porcine reproductive and respiratory syndrome virus (HP-PRRSV), in MARC-145 cells, by inhibiting the synthesis of the HuN4 complement RNA. The antiviral effects of the simian SAMHD1 protein were nearly equivalent to those of porcine SAMHD1 in the HuN4-infected MARC-145 cells. Phosphorylation analysis of SAMHD1 showed that overexpressed SAMHD1 protein was in primarily an unphosphorylated state. SAMHD1 overexpression increased the transcript abundance of IFN-stimulated genes ISG15 and ISG56. The mRNA levels of SAMHD1 and ISGs were significantly increased in porcine alveolar macrophages infected with HP-PRRSV. SAMHD1 protein level was also elevated, and the protein was not phosphorylated during infection. Collectively, our data indicate that SAMHDI inhibits HP-PRRSV proliferation through inhibiting the replication of HP-PRRSV. SAMHD1 might be the protein participating in the IFN signaling and is thus an important immunoregulatory protein in innate immunity. PMID:25106914

  8. [Pulmonary alveolar microlithiasis: Report of one case].

    PubMed

    Fernández F, Cristina; Salinas F, Mauricio; de Grazia K, José Andrés; Díaz P, Juan Carlos

    2014-05-01

    Pulmonary alveolar microlithiasis is an extremely rare disease characterized by intra-alveolar accumulation of calcified spherical particles (called microliths), due to a mutation of the gene encoding a membrane transport protein of the alveolar surface. Most patients are asymptomatic at diagnosis. The course of the disease is slowly progressive, with development of pulmonary fibrosis and respiratory failure. The "sandstorm" pattern is the characteristic finding of this disease. We report a 39-year-old female presenting with progressive dyspnea. A chest X ray showed ground-glass opacities and a high resolution CT scan showed numerous calcified lung micronodules. A surgical lung biopsy confirmed the diagnosis of pulmonary alveolar microlithiasis. PMID:25427025

  9. Porcine prion protein amyloid

    PubMed Central

    Hammarström, Per; Nyström, Sofie

    2015-01-01

    ABSTRACT Mammalian prions are composed of misfolded aggregated prion protein (PrP) with amyloid-like features. Prions are zoonotic disease agents that infect a wide variety of mammalian species including humans. Mammals and by-products thereof which are frequently encountered in daily life are most important for human health. It is established that bovine prions (BSE) can infect humans while there is no such evidence for any other prion susceptible species in the human food chain (sheep, goat, elk, deer) and largely prion resistant species (pig) or susceptible and resistant pets (cat and dogs, respectively). PrPs from these species have been characterized using biochemistry, biophysics and neurobiology. Recently we studied PrPs from several mammals in vitro and found evidence for generic amyloidogenicity as well as cross-seeding fibril formation activity of all PrPs on the human PrP sequence regardless if the original species was resistant or susceptible to prion disease. Porcine PrP amyloidogenicity was among the studied. Experimentally inoculated pigs as well as transgenic mouse lines overexpressing porcine PrP have, in the past, been used to investigate the possibility of prion transmission in pigs. The pig is a species with extraordinarily wide use within human daily life with over a billion pigs harvested for human consumption each year. Here we discuss the possibility that the largely prion disease resistant pig can be a clinically silent carrier of replicating prions. PMID:26218890

  10. Management of the alveolar cleft.

    PubMed

    Santiago, Pedro E; Schuster, Lindsay A; Levy-Bercowski, Daniel

    2014-04-01

    Orthopedic and orthodontic management of patients born with clefts of the lip, alveolus and palate is based on the application of basic biomechanical principles adapted to the individualized cleft anatomy. This article focuses on orthopedic and orthodontic preparation for 2 stages of interdisciplinary orthodontic/surgical cleft care: presurgical infant orthopedics (nasoalveolar molding) for lip/alveolus/nasal surgical repair and maxillary arch preparation for secondary alveolar bone grafting. These preparatory stages of orthopedic/orthodontic therapy are undertaken with the goal of restoring normal anatomic relationships to assist the surgeon in providing the best possible surgical care. PMID:24607190

  11. Diffuse Alveolar Hemorrhage Associated with Warfarin Therapy

    PubMed Central

    Kaya, Bülent; Yildiz, Ibrahim; Baha, Reshat Mehmet; Zeytun, Neslihan Ebru Eryaşar; Yetisgen, Azize

    2015-01-01

    Diffuse alveolar hemorrhage (DAH) is a life-threatening clinical pathologic syndrome caused by a variety of diseases. We report a case of DAH related to therapy of warfarin use. In this case report, we present the diffuse alveolar hemorrhage case as a rare and life-threatening complication of warfarin. PMID:26347781

  12. Synthesis of Dipalmitoyl Lecithin by Alveolar Macrophages

    PubMed Central

    Mason, Robert J.; Huber, Gary; Vaughan, Martha

    1972-01-01

    A reliable, relatively simple method for isolation and quantification of disaturated lecithins is described. In rabbit lung, 34% of the lecithins were disaturated, in alveolar macrophages, 19%. More than 95% of the fatty acids of the disaturated lecithins from lung and alveolar macrophages was palmitic. Hence, the disaturated lecithins from these sources were essentially all dipalmitoyl lecithin. Both heterophils and alveolar macrophages incorporated 14C-labeled choline and palmitate into disaturated lecithins. Liver slices in which only about 1% of the lecithins were disaturated incorporated very little of these precursors into this fraction. Of the palmitate incorporated in vitro into disaturated lecithins by alveolar macrophages, heterophils, and lung slices, 37% was in the 1 position. In disaturated lecithins isolated from pulmonary lavage fluid, alveolar macrophages, and lung of rabbit 8-12 hr after a single intravenous injection of palmitic-1-14C acid, 45% of the 14C was in position 1. At earlier times, from 20-240 min after injection, the distribution of 14C was similar in the samples from lung, but in those from alveolar macrophages and lavage fluid, the percentage in position 1 was slightly lower. Glycerol-U-14C was incorporated into disaturated lecithins by alveolar macrophages and by lung slices in vitro. Both tissues incorporated very little label from ethanolamine or from methyl-labeled methionine into this fraction. All of the data are consistent with the view that alveolar macrophages synthesize dipalmitoyl lecithin via the cytidine diphosphate-choline pathway. PMID:5066597

  13. Pulse granuloma of the alveolar ridge.

    PubMed

    Mincer, H H; McCoy, J M; Turner, J E

    1979-08-01

    Six examples of pulse granulomas of the alveolar ridge are presented. The lesion consists of a foreign-body granuloma containing identifiable particles of leguminous foods. The vegetable matter is introduced through an alveolar defect, usually a postextraction socket. Simple curettage is apparently adequate treatment to effect cure. PMID:382018

  14. Diffuse alveolar hemorrhage following alemtuzumab.

    PubMed

    Sachdeva, Ashutosh; Matuschak, George M

    2008-06-01

    This study describes an unusual patient with X-linked Alport syndrome (XLAS) in whom diffuse alveolar hemorrhage (DAH) developed as a complication of alemtuzumab therapy following renal transplantation. A 26-year-old man with XLAS underwent retransplantation with a cadaveric renal allograft. He received alemtuzumab therapy as a part of an immunosuppressive induction protocol, and dyspnea and hemoptysis developed. A chest CT scan showed diffuse alveolar opacities. Bronchoscopy was performed to determine the cause of hemoptysis and hypoxia. BAL showed a characteristic increasingly bloody return in the sequential aliquots. There was no growth of pathogenic bacteria or evidence of opportunistic infection. Clinical improvement occurred with the initiation of steroids, and the patient required short-term mechanical ventilation for acute respiratory failure. To our knowledge, this is the first reported case of DAH associated with use of alemtuzumab therapy, although other pulmonary toxicities have been described. The prevalence of this form of pulmonary toxicity is unclear and requires further systematic study. PMID:18574290

  15. Leukotriene B4 receptors on guinea pig alveolar eosinophils

    SciTech Connect

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

    1991-09-01

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

  16. Detection and Characterization of Porcine Endogenous Retrovirus in Porcine Plasma and Porcine Factor VIII

    PubMed Central

    Takefman, Daniel M.; Wong, Susan; Maudru, Thomas; Peden, Keith; Wilson, Carolyn A.

    2001-01-01

    The pig genome contains porcine endogenous retroviruses (PERVs) capable of infecting human cells. Detection of infectious retrovirus in porcine peripheral blood mononuclear cells and endothelial cells suggested to us that pig plasma is likely to contain PERV. Both PERV env sequences and viral reverse transcriptase (RT) activity were detected in all plasma samples isolated from four NIH minipigs. To detect infectious virus from plasma, we performed a culture assay using three cell lines of feline, swine, and human origin that had previously been shown to be permissive for PERV. Infectious virus was successfully cultured from all four NIH minipig plasmas on the swine cell line ST-IOWA. Using RT-PCR with env-specific primers, we could detect expression of PERV class C envelope in the supernatant of ST-IOWA cells that had been exposed to each pig plasma. We next examined a pig plasma derivative, Hyate:C (porcine factor VIII), and found evidence of PERV particles, since all six lots examined were positive for PERV RNA and RT activity. However, infectious virus could not be detected in clinical lots of Hyate:C, suggesting that the manufacturing process might reduce the load of infectious virus to levels below detectable limits of the assay. Detection of infectious virus in porcine plasma confirms and extends the previous findings that certain porcine cells express PERV when manipulated in vitro and clearly demonstrates that there are porcine cells that express infectious PERV constitutively in vivo. PMID:11312325

  17. Vertical Alveolar Ridge Augmentation by Distraction Osteogenesis

    PubMed Central

    Kumar, N. Nanda; Ravindran, C.

    2015-01-01

    Introduction Compromised alveolar ridge in vertical and horizontal dimension is a common finding in patients visiting practitioners for dental prosthesis. Various treatment modalities are available for correction of deficient ridges among which alveolar distraction osteogenesis is one. Aim To study the efficacy of alveolar distraction osteogenesis in augmentation of alveolar ridges deficient in vertical dimension. Materials and Methods Ten patients aged 16 to 46 years with deficient alveolar ridge underwent ridge augmentation in 11 alveolar segments using the distraction osteogenesis method. For each patient a custom made distraction device was fabricated. The device was indigenously manufactured with SS-316 (ISO 3506). Results The vertical bone gain reached more than 10mm without the use of bone transplantation. Certain complications like incorrect vector of distraction, paresthesia, pain and loss of transport segment were encountered during the course of the study. Conclusion Alveolar vertical distraction osteogenesis is a reliable and predictable technique for both hard and soft tissue genesis. Implant placement is feasible with primary stability in neogenerated bone at the level of the distracted areas. PMID:26816991

  18. Infection of porcine bone marrow-derived macrophages by porcine respiratory and reproductive syndrome virus impairs phagosomal maturation.

    PubMed

    Chaudhuri, Sibapriya; McKenna, Neil; Balce, Dale R; Yates, Robin M

    2016-03-01

    Porcine reproductive and respiratory syndrome virus (PRRSV), a positive-sense, ssRNA virus of the genus Arterivirus, is a devastating disease of swine worldwide. Key early targets of PRRSV infection in pigs include professional phagocytes in the lung, such as alveolar and interstitial macrophages and dendritic cells, the dysfunction of which is believed to be responsible for much of the associated mortality. In order to study the effect of virus infection on phagocyte function, the development of a robust, reproducible model would be advantageous. Given the limitations of current models, we set out to develop a porcine bone marrow-derived macrophage (PBMMΦ) cell model to study phagosomal maturation and function during PRRSV infection. Derivation of PBMMΦs from marrow using cultured L929 fibroblast supernatant produced a homogeneous population of cells that exhibited macrophage-like morphology and proficiency in Fc-receptor-mediated phagocytosis and phagosomal maturation. PBMMΦs were permissive to PRRSV infection, resulting in a productive infection that peaked at 24 h. Assessment of the effect of PRRSV infection on the properties of phagosomal maturation in PBMMΦs revealed a significant decrease in phagosomal proteolysis and lowered production of reactive oxygen species, but no change in PBMMΦ viability, phagocytosis or the ability of phagosomes to acidify. In this study, we present a new model to investigate PRRSV infection of phagocytes, which demonstrates a significant effect on phagosomal maturation with the associated implications on proper macrophage function. This model can also be used to study the effect on the phagosomal microenvironment of infection by other viruses targeting porcine macrophages. PMID:26702996

  19. Enhancing neutralizing antibody production by an interferon-inducing porcine reproductive and respiratory syndrome virus strain.

    PubMed

    Wang, Rong; Xiao, Yueqiang; Opriessnig, Tanja; Ding, Yi; Yu, Ying; Nan, Yuchen; Ma, Zexu; Halbur, Patrick G; Zhang, Yan-Jin

    2013-11-12

    Porcine reproductive and respiratory syndrome (PRRS) virus (PRRSV) continues to cause substantial economic losses to the global swine industry. PRRSV appears to inhibit synthesis of type I interferons (IFNs), such as IFN-α and -β, which are critical for the innate immunity and play an important role in the modulation of adaptive immunity. An atypical PRRSV strain, A2MC2, is able to induce type I IFNs in vitro. In this study, A2MC2 induction of neutralizing antibodies in vivo was compared with the Ingelvac PRRS modified live virus (MLV) vaccine strain and VR-2385 (a moderate virulent strain). Three-week-old pigs were exposed to these PRRSV strains via intranasal or intramuscular routes to also account for a possible effect of inoculation routes. The interferon-inducing A2MC2 resulted in earlier onset and significantly higher levels of PRRSV neutralizing antibodies than the MLV. In addition, the A2MC2-induced neutralizing antibodies were capable of neutralizing VR-2385, a heterologous strain. The pigs exposed via intranasal route had higher titers of neutralizing antibodies than those injected via intramuscular route. Macroscopic and microscopic lung lesions 14 days post-exposure indicated that A2MC2 had similar virulence in vivo as VR-2385. Pulmonary alveolar macrophages (PAMs) collected during the necropsy 14 days post-exposure in the A2MC2 group had higher level expression of IFN-γ than the MLV group. These results indicate that A2MC2 can be further explored for development of an improved vaccine against PRRS. PMID:24063978

  20. Secondary Alveolar Bone Grafting (CLEFTSiS) 2007-2010.

    PubMed

    Paterson, Michael; Rae, Jennifer; Paterson, Paul; Gilgrass, Toby; Devlin, Mark; McIntyre, Grant

    2016-03-01

    Objective To determine whether alveolar bone graft outcomes for unilateral and bilateral cleft lip and palate patients have continued to improve since the reorganization of cleft services in Scotland in 2000. Design Retrospective analysis of postoperative anterior occlusal radiographs. Patients and Participants Eighty-one of 106 patients who were eligible for alveolar bone grafting between 2007 and 2010 had suitable postoperative radiographs available. Interventions Twenty-seven percent of the patients (n = 22) had presurgical orthodontic intervention. All patients underwent alveolar bone grafting with bone harvested from the iliac crest. Main Outcome Measures The Kindelan bone-fill index was used to evaluate success. Weighted kappa statistics were used to assess intra- and interobserver reproducibility. A comparison was made with results from 2000 to 2004 to assess any improvement. Chi-square tests (or Fisher exact test) were used to determine whether outcomes differed depending on the laterality of the cleft, use of presurgical expansion, or age at bone grafting. Results Interobserver scoring agreement was good (weighted kappa = .383). Intraobserver reproducibility was greater (weighted kappas of .835 and .620). Success was achieved in 99% of bone grafts, compared with 76% in the period from 2000 to 2004 (P < .001). There was no statistically significant relationship between the laterality of the cleft (P = 1.000), use of presurgical expansion (P = 1.000), or age at time of bone grafting and outcome (P = .259). Conclusion Scottish secondary alveolar bone graft outcomes improved during 2007 to 2010 in comparison to the 2000 to 2004 results. PMID:26914161

  1. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Porcine animal. 1230.611 Section 1230.611 Agriculture... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.611 Porcine animal. The term Porcine animal means a swine, that is raised: (a) As a feeder pig, that is, a young pig sold...

  2. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Porcine animal. 1230.611 Section 1230.611 Agriculture... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.611 Porcine animal. The term Porcine animal means a swine, that is raised: (a) As a feeder pig, that is, a young pig sold...

  3. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Porcine animal. 1230.611 Section 1230.611 Agriculture... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.611 Porcine animal. The term Porcine animal means a swine, that is raised: (a) As a feeder pig, that is, a young pig sold...

  4. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Porcine animal. 1230.611 Section 1230.611 Agriculture... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.611 Porcine animal. The term Porcine animal means a swine, that is raised: (a) As a feeder pig, that is, a young pig sold...

  5. 7 CFR 1230.611 - Porcine animal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false Porcine animal. 1230.611 Section 1230.611 Agriculture... CONSUMER INFORMATION Procedures for the Conduct of Referendum Definitions § 1230.611 Porcine animal. The term Porcine animal means a swine, that is raised: (a) As a feeder pig, that is, a young pig sold...

  6. Porcine Dentin Sialophosphoprotein

    PubMed Central

    Yamakoshi, Yasuo; Lu, Yuhe; Hu, Jan C.-C.; Kim, Jung-Wook; Iwata, Takanori; Kobayashi, Kazuyuki; Nagano, Takatoshi; Yamakoshi, Fumiko; Hu, Yuanyuan; Fukae, Makoto; Simmer, James P.

    2008-01-01

    Dentin sialophosphoprotein (DSPP) is critical for proper mineralization of tooth dentin, and mutations in DSPP cause inherited dentin defects. Dentin phosphoprotein (DPP) is the C-terminal cleavage product of DSPP that binds collagen and induces intrafibrillar mineralization. We isolated DPP from individual pigs and determined that its N-terminal and C-terminal domains are glycosylated and that DPP averages 155 phosphates per molecule. Porcine DPP is unstable at low pH and high temperatures, and complexing with collagen improves its stability. Surprisingly, we observed DPP size variations on SDS-PAGE for DPP isolated from individual pigs. These variations are not caused by differences in proteolytic processing or degrees of phosphorylation or glycosylation, but rather to allelic variations in Dspp. Characterization of the DPP coding region identified 4 allelic variants. Among the 4 alleles, 27 sequence variations were identified, including 16 length polymorphisms ranging from 3 to 63 nucleotides. None of the length variations shifted the reading frame, and all localized to the highly redundant region of the DPP code. The 4 alleles encode DPP domains having 551, 575, 589, or 594 amino acids and completely explain the DPP size variations. DPP length variations are polymorphic and are not associated with dentin defects. PMID:18359767

  7. Fatal Alveolar Echinococcosis of the Lumbar Spine

    PubMed Central

    Keutgens, Aurore; Simoni, Paolo; Detrembleur, Nancy; Frippiat, Frédéric; Giot, Jean-Baptiste; Spirlet, François; Aghazarian, Saro; Descy, Julie; Meex, Cécile; Huynen, Pascale; Melin, Pierrette; Müller, Norbert; Gottstein, Bruno; Carlier, Yves

    2013-01-01

    For the last 10 years, the southern part of Belgium has been recognized as a low-risk area of endemicity for alveolar echinococcosis. This infection, caused by Echinococcus multilocularis, usually induces a severe liver condition and can sometimes spread to other organs. However, alveolar echinococcosis involving bones has been described only very rarely. Here, a fatal case of spondylodiscitis due to E. multilocularis contracted in southern Belgium is reported. PMID:23175265

  8. Telomere dysfunction causes alveolar stem cell failure.

    PubMed

    Alder, Jonathan K; Barkauskas, Christina E; Limjunyawong, Nathachit; Stanley, Susan E; Kembou, Frant; Tuder, Rubin M; Hogan, Brigid L M; Mitzner, Wayne; Armanios, Mary

    2015-04-21

    Telomere syndromes have their most common manifestation in lung disease that is recognized as idiopathic pulmonary fibrosis and emphysema. In both conditions, there is loss of alveolar integrity, but the underlying mechanisms are not known. We tested the capacity of alveolar epithelial and stromal cells from mice with short telomeres to support alveolar organoid colony formation and found that type 2 alveolar epithelial cells (AEC2s), the stem cell-containing population, were limiting. When telomere dysfunction was induced in adult AEC2s by conditional deletion of the shelterin component telomeric repeat-binding factor 2, cells survived but remained dormant and showed all the hallmarks of cellular senescence. Telomere dysfunction in AEC2s triggered an immune response, and this was associated with AEC2-derived up-regulation of cytokine signaling pathways that are known to provoke inflammation in the lung. Mice uniformly died after challenge with bleomycin, underscoring an essential role for telomere function in AEC2s for alveolar repair. Our data show that alveoloar progenitor senescence is sufficient to recapitulate the regenerative defects, inflammatory responses, and susceptibility to injury that are characteristic of telomere-mediated lung disease. They suggest alveolar stem cell failure is a driver of telomere-mediated lung disease and that efforts to reverse it may be clinically beneficial. PMID:25840590

  9. Evaluation of the Human Host Range of Bovine and Porcine Viruses that may Contaminate Bovine Serum and Porcine Trypsin Used in the Manufacture of Biological Products

    PubMed Central

    Marcus-Sekura, Carol; Richardson, James C.; Harston, Rebecca K.; Sane, Nandini; Sheets, Rebecca L.

    2011-01-01

    Current U.S. requirements for testing cell substrates used in production of human biological products for contamination with bovine and porcine viruses are U.S. Department of Agriculture (USDA) 9CFR tests for bovine serum or porcine trypsin. 9CFR requires testing of bovine serum for seven specific viruses in six families (immunofluorescence) and at least 2 additional families non-specifically (cytopathicity and hemadsorption). 9CFR testing of porcine trypsin is for porcine parvovirus. Recent contaminations suggest these tests may not be sufficient. Assay sensitivity was not the issue for these contaminations that were caused by viruses/virus families not represented in the 9CFR screen. A detailed literature search was undertaken to determine which viruses that infect cattle or swine or bovine or porcine cells in culture also have human host range [ability to infect humans or human cells in culture] and to predict their detection by the currently used 9CFR procedures. There are more viruses of potential risk to biological products manufactured using bovine or porcine raw materials than are likely to be detected by 9CFR testing procedures; even within families, not all members would necessarily be detected. Testing gaps and alternative methodologies should be evaluated to continue to ensure safe, high quality human biologicals. PMID:22000165

  10. Porcine Reproductive and Respiratory Syndrome

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome (PRRS) first appeared in the late 1980s, though serologic evidence indicates that it had been circulating in swine for some time prior to being recognized. PRRS has since become a highly significant infectious disease affecting swine production worldwid...

  11. Chloride-dependent secretion of alveolar wall liquid determined by optical-sectioning microscopy.

    PubMed

    Lindert, Jens; Perlman, Carrie E; Parthasarathi, Kaushik; Bhattacharya, Jahar

    2007-06-01

    The liquid layer lining the pulmonary alveolar wall critically determines the lung's immune defense against inhaled pathogens, because it provides a liquid milieu in the air-filled alveolus for dispersal of immune cells and defensive surfactant proteins. However, mechanisms underlying formation of the liquid are unknown. We achieved visualization of the alveolar wall liquid (AWL) in situ in mouse lungs by means of optical-sectioning microscopy. Continuous liquid secretion was present in alveoli of wild-type (WT) mice under baseline conditions. This secretion was blocked by inhibitors of the cystic fibrosis transmembrane regulator (CFTR). The secretion was absent in Cftr(-/-) mice, and it was blocked when chloride was depleted from the perfusate of WT mice, providing the first evidence that CFTR-dependent chloride secretion causes AWL formation. Injected microparticles demonstrated flow of the AWL. The flow was blocked by CFTR inhibition and was absent in Cftr(-/-) mice. We conclude that CFTR-dependent liquid secretion is present in alveoli of the adult mouse. Defective alveolar secretion might impair alveolar immune defense and promote alveolar disease. PMID:17290033

  12. [Inferior alveolar nerve repositioning in implant surgery].

    PubMed

    Ardekian, L; Salnea, J; Abu el-Naaj, I; Gutmacher, T; Peled, M

    2001-04-01

    Severe resorption of the posterior mandible possesses one of the most difficult restorative challenges to the implant surgery today. This resorption may prevent the placement of dental implants without the potentially damage to the inferior alveolar nerve. To create the opportunity of insertion dental implants of adequately length in those cases, the technique of nerve repositioning has been advocated. The purpose of this article is to describe two cases of nerve repositioning combined with placement of dental implants. Both cases showed appropriate postoperative healing without damage to the inferior alveolar nerve. The inferior alveolar nerve repositioning technique seems to be an acceptable alternative to augmentation procedure prior to dental implants placement in cases exhibiting atrophic posterior mandibular ridges. PMID:11494807

  13. Lateralization Technique and Inferior Alveolar Nerve Transposition

    PubMed Central

    Sanches, Marco Antonio; Ramalho, Gabriel Cardoso; Manzi, Marcello Roberto

    2016-01-01

    Bone resorption of the posterior mandible can result in diminished bone edge and, therefore, the installation of implants in these regions becomes a challenge, especially in the presence of the mandibular canal and its contents, the inferior alveolar nerve. Several treatment alternatives are suggested: the use of short implants, guided bone regeneration, appositional bone grafting, distraction osteogenesis, inclined implants tangential to the mandibular canal, and the lateralization of the inferior alveolar nerve. The aim was to elucidate the success rate of implants in the lateralization technique and in inferior alveolar nerve transposition and to determine the most effective sensory test. We conclude that the success rate is linked to the possibility of installing implants with long bicortical anchor which favors primary stability and biomechanics. PMID:27433360

  14. Characterization of the microRNAome in Porcine Reproductive and Respiratory Syndrome Virus Infected Macrophages

    PubMed Central

    A. Hicks, Julie; Yoo, Dongwan; Liu, Hsiao-Ching

    2013-01-01

    Porcine Reproductive and Respiratory Syndrome Virus (PRRSV), a member of the arterivirus family, is the causative agent of Porcine Reproductive and Respiratory Syndrome (PRRS). PRRS is characterized by late term abortions and respiratory disease, particularly in young pigs. Small regulatory RNAs termed microRNA (miRNA) are associated with gene regulation at the post-transcriptional level. MiRNAs are known to play many diverse and complex roles in viral infections. To discover the impact of PRRSV infections on the cellular miRNAome, Illumina deep sequencing was used to construct small RNA expression profiles from in vitro cultured PRRSV-infected porcine alveolar macrophages (PAMs). A total of forty cellular miRNAs were significantly differentially expressed within the first 48 hours post infection (hpi). The expression of six miRNAs, miR-30a-3p, miR-132, miR-27b*, miR-29b, miR-146a and miR-9-2, were altered at more than one time point. Target gene identification suggests that these miRNAs are involved in regulating immune signaling pathways, cytokine, and transcription factor production. The most highly repressed miRNA at 24 hpi was miR-147. A miR-147 mimic was utilized to maintain miR-147 levels in PRRSV-infected PAMs. PRRSV replication was negatively impacted by high levels of miR-147. Whether down-regulation of miR-147 is directly induced by PRRSV or if it is part of the cellular response and PRRSV indirectly benefits remains to be determined. No evidence could be found of PRRSV-encoded miRNAs. Overall, the present study has revealed that a large and diverse group of miRNAs are expressed in swine alveolar macrophages and that the expression of a subset of these miRNAs is altered in PRRSV infected macrophages. PMID:24339989

  15. ALVEOLAR BREATH SAMPLING AND ANALYSIS IN HUMAN EXPOSURE ASSESSMENT STUDIES

    EPA Science Inventory

    Alveolar breath sampling and analysis can be extremely useful in exposure assessment studies involving volatile organic compounds (VOCs). Over recent years scientists from the EPA's National Exposure Research Laboratory have developed and refined an alveolar breath collection ...

  16. Increased alveolar plasminogen activator in early asbestosis

    SciTech Connect

    Cantin, A.; Allard, C.; Begin, R.

    1989-03-01

    Alveolar macrophage-derived plasminogen activator (PA) activity is decreased in some chronic interstitial lung diseases such as idiopathic pulmonary fibrosis and sarcoidosis but increased in experimental models of acute alveolitis. Although asbestos fibers can stimulate alveolar macrophages (AM) to release PA in vitro, the effect of chronic asbestos exposure of the lower respiratory tract on lung PA activity remains unknown. The present study was designed to evaluate PA activity of alveolar macrophages and bronchoalveolar lavage (BAL) fluid in asbestos-exposed sheep and asbestos workers. Forty-three sheep were exposed to either 100 mg UICC chrysotile B asbestos in 100 ml phosphate-buffered saline (PBS) or to 100 ml PBS by tracheal infusion every 2 wk for 18 months. At Month 18, chest roentgenograms were analyzed and alveolar macrophage and extracellular fluid PA activity were measured in samples obtained by BAL. Alveolar macrophage PA activity was increased in the asbestos-exposed sheep compared to control sheep (87.2 +/- 17.3 versus 41.1 +/- 7.2 U/10(5) AM-24 h, p less than 0.05) as was the BAL fluid PA activity (674.9 +/- 168.4 versus 81.3 +/- 19.7 U/mg alb-24 h, p less than 0.01). Among the asbestos-exposed sheep, 10 had normal chest roentgenograms (Group SA) and 15 had irregular interstitial opacities (Group SB). Strikingly, whereas Group SA did not differ from the control group in BAL cellularity or PA activity, Group SB had marked increases in alveolar macrophages (p less than 0.005), AM PA activity (p less than 0.02), and BAL PA activity (p less than 0.001) compared to the control group.

  17. Remodeling of alveolar septa after murine pneumonectomy.

    PubMed

    Ysasi, Alexandra B; Wagner, Willi L; Bennett, Robert D; Ackermann, Maximilian; Valenzuela, Cristian D; Belle, Janeil; Tsuda, Akira; Konerding, Moritz A; Mentzer, Steven J

    2015-06-15

    In most mammals, removing one lung (pneumonectomy) results in the compensatory growth of the remaining lung. In mice, stereological observations have demonstrated an increase in the number of mature alveoli; however, anatomic evidence of the early phases of alveolar growth has remained elusive. To identify changes in the lung microstructure associated with neoalveolarization, we used tissue histology, electron microscopy, and synchrotron imaging to examine the configuration of the alveolar duct after murine pneumonectomy. Systematic histological examination of the cardiac lobe demonstrated no change in the relative frequency of dihedral angle components (Ends, Bends, and Junctions) (P > 0.05), but a significant decrease in the length of a subset of septal ends ("E"). Septal retraction, observed in 20-30% of the alveolar ducts, was maximal on day 3 after pneumonectomy (P < 0.01) and returned to baseline levels within 3 wk. Consistent with septal retraction, the postpneumonectomy alveolar duct diameter ratio (Dout:Din) was significantly lower 3 days after pneumonectomy compared to all controls except for the detergent-treated lung (P < 0.001). To identify clumped capillaries predicted by septal retraction, vascular casting, analyzed by both scanning electron microscopy and synchrotron imaging, demonstrated matted capillaries that were most prominent 3 days after pneumonectomy. Numerical simulations suggested that septal retraction could reflect increased surface tension within the alveolar duct, resulting in a new equilibrium at a higher total energy and lower surface area. The spatial and temporal association of these microstructural changes with postpneumonectomy lung growth suggests that these changes represent an early phase of alveolar duct remodeling. PMID:26078396

  18. Interleukin-5 is the predominant cytokine produced by peripheral blood mononuclear cells in alveolar echinococcosis.

    PubMed Central

    Sturm, D; Menzel, J; Gottstein, B; Kern, P

    1995-01-01

    An involvement of cellular immunity in alveolar echinococcosis is strongly suggested by the intense granulomatous infiltrations observed around the hepatic parasite lesions. However, the basis of cellular immunoregulation in patient with alveolar echinococcosis is poorly understood. The present report shows a comparative analysis of lymphoid cell function in peripheral blood mononuclear cells (PBMC) of 16 patients with alveolar echinococcosis and of healthy individuals. Our in vitro restimulation studies with crude Echinococcus multilocularis antigen demonstrated that PBMC from patients with alveolar echinococcosis were responsive to challenge with parasitic antigen as measured by lymphoid cell proliferation. In this system, we also evaluated cytokine expression at the gene and protein levels after stimulation with E. multilocularis antigen. Analysis of cytokine mRNA expression revealed distinct patterns of cytokine expression in patients and normal donors. By using reverse transcriptase PCR, we could demonstrate that the TH1 cytokine transcripts interleukin-2 (IL-2) and gamma interferon (IFN-gamma) are present in PBMC from patients with alveolar echinococcosis. Moreover, it was found that stimulation with E. multilocularis antigen induced or enhanced the expression of the TH2 cytokine IL-3, IL-4, IL-10, and especially IL-5 mRNAs in PBMC from 13 of 16 patients with alveolar echinococcosis. Two patients who were examined after radical surgery, as well as another patient with a stable course of the disease under continuous chemotherapy, were not able to generate the same pattern of cytokine response and had no evidence of IL-5 mRNA synthesis. In contrast to the frequent expression of TH2 cytokine mRNAs observed in patients with alveolar echinococcosis, PBMC cultures from normal donors showed prominent IL-2 and IFN-gamma mRNA expression but weak IL-3, IL-4, and IL-10 mRNA expression. Most interestingly, IL-5 mRNA was substantially absent in PBMC from healthy

  19. Rehabilitation of masticatory function improves the alveolar bone architecture of the mandible in adult rats.

    PubMed

    Mavropoulos, Anestis; Odman, Anna; Ammann, Patrick; Kiliaridis, Stavros

    2010-09-01

    Masticatory functional changes have been shown to influence the quantity and quality of the alveolar bone during growth. This study was designed to investigate the effect of masticatory function rehabilitation on the morphology and the trabecular architecture of the mandibular alveolar bone after cessation of growth. Forty-four Sprague-Dawley male rats received soft diet in order to develop masticatory muscle hypofunction. After 21 weeks, after cessation of growth, the animals were divided into two groups: the first group continued receiving soft diet for six more weeks (hypofunction group), while the second group changed to ordinary (hard) diet with the aim to restore a normal masticatory function (rehabilitation group). A third group of 16 male rats (normal group) received ordinary (hard) diet during the whole experimental period and served as control. Micro-tomographic histomorphometry was used to evaluate the architecture of the mandibular alveolar bone (e.g. bone volume fraction, trabecular thickness, trabecular separation, etc.) at the end of the experiment (27 weeks). The height and width of the alveolar process were measured as well. The alveolar process trabecular bone volume fraction (BV/TV) was lower for the animals of the hypofunctional group as compared to those of the normal (p<0.01) and the rehabilitation (p<0.05) groups. Despite the significant improvement observed in the rehabilitation group, their BV/TV was lower in comparison to the normal group (p<0.05) at the end of this experiment. All the other micro-tomographic parameters followed the same pattern of change between groups; values of the rehabilitation group were between the values of the two other groups, differing significantly from both of them. The alveolar process was significantly shorter in the normal group in comparison to both the hypofunctional and rehabilitation groups (p<0.05). On the other hand, both the normal and rehabilitation groups were had a wider alveolar process than the

  20. Blood gas stability and hematological changes in experimentally-induced acute porcine pleuropneumonia.

    PubMed Central

    Kiorpes, A L; Mirsky, M L; MacWilliams, P S; Bäckström, L R; Collins, M T

    1989-01-01

    Blood gas and hematological responses to acute, mild Actinobacillus pleuropneumoniae infection of growing pigs was studied. Six pigs (average weight 10.1 kg) were experimentally infected intranasally with A. pleuropneumoniae serotype 5. Four pigs served as controls. Rectal temperatures and arterial blood for gas analysis and hematology were taken at 0, 8, 16, 24, 48 and 72 h postinfection. All infected pigs became febrile showing clinical signs typical of mild to moderate porcine pleuropneumonia; controls remained asymptomatic. Neutrophilia with bands and lymphopenia were observed only in infected pigs. Arterial partial pressures of O2 and CO2, and pH did not change in infected pigs. All pigs were killed after 72 h, and lungs were examined and cultured. Gross and microscopic lesions consistent with porcine pleuropneumonia were seen in 3/6 and 5/6 infected lungs, respectively. Control lungs were grossly normal with no histological evidence of pleuropneumonia. We conclude that in mild, acute porcine pleuropneumonia as established experimentally, a leukogram typical of acute inflammation and stress is seen; however, hypoxemia and alveolar hypoventilation are not features of this form of the disease. PMID:2914231

  1. Porcine reproductive and respiratory syndrome virus infection triggers HMGB1 release to promote inflammatory cytokine production

    SciTech Connect

    Duan, Erzhen; Wang, Dang; Luo, Rui; Luo, Jingyi; Gao, Li; Chen, Huanchun; Fang, Liurong Xiao, Shaobo

    2014-11-15

    The high mobility group box 1 (HMGB1) protein is an endogenous damage-associated molecular pattern (DAMP) molecule involved in the pathogenesis of various infectious agents. Based on meta-analysis of all publicly available microarray datasets, HMGB1 has recently been proposed as the most significant immune modulator during the porcine response to porcine reproductive and respiratory syndrome virus (PRRSV) infection. However, the function of HMGB1 in PRRSV pathogenesis is unclear. In this study, we found that PRRSV infection triggers the translocation of HMGB1 from the nucleus to the extracellular milieu in MARC-145 cells and porcine alveolar macrophages. Although HMGB1 has no effect on PRRSV replication, HMGB1 promotes PRRSV-induced NF-κB activation and subsequent expression of inflammatory cytokines through receptors RAGE, TLR2 and TLR4. Our findings show that HMGB1 release, triggered by PRRSV infection, enhances the efficiency of virus-induced inflammatory responses, thereby providing new insights into the pathogenesis of PRRSV infection. - Highlights: • PRRSV infection triggers HMGB1 release from MARC-145 cells and PAMs. • HMGB1 does not significantly affect PRRSV proliferation. • HMGB1 is involved in PRRSV-induced NF-κB activation and inflammatory responses. • HMGB1 promotes PRRSV-induced inflammatory responses through TLR2/4 and RAGE.

  2. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis.

    PubMed

    Tokman, Sofya; Hahn, M Frances; Abdelrazek, Hesham; Panchabhai, Tanmay S; Patel, Vipul J; Walia, Rajat; Omar, Ashraf

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus. PMID:27213073

  3. Pulmonary alveolar microlithiasis: a rare case report.

    PubMed

    Ahmad, Kaleem; Kumar Gupta, Mukesh; Dhungel, Kanchan; Lal Sah, Panna; Ansari, Sajid; Kumar Rauniyar, Raj

    2013-09-01

    Pulmonary alveolar microlithiasis is an uncommon infiltrative pulmonary disease characterized by deposition of microliths in the alveoli. We present the case of a young adult with complaints of shortness of breath on exertion. Chest radiograph showed innumerable small, dense nodules, diffusely involving both the lungs - predominantly in the lower zones. High-resolution CT scan illustrated widespread intra-alveolar microliths, diffuse ground-glass attenuation areas, septal thickening, and black pleural lines - predominantly in the basal regions. Transbronchial biopsy confirmed the diagnosis. PMID:24174699

  4. Pulmonary Alveolar Microlithiasis: A Rare Case Report

    PubMed Central

    Ahmad, Kaleem; Kumar Gupta, Mukesh; Dhungel, Kanchan; Lal Sah, Panna; Ansari, Sajid; Kumar Rauniyar, Raj

    2013-01-01

    Pulmonary alveolar microlithiasis is an uncommon infiltrative pulmonary disease characterized by deposition of microliths in the alveoli. We present the case of a young adult with complaints of shortness of breath on exertion. Chest radiograph showed innumerable small, dense nodules, diffusely involving both the lungs - predominantly in the lower zones. High-resolution CT scan illustrated widespread intra-alveolar microliths, diffuse ground-glass attenuation areas, septal thickening, and black pleural lines - predominantly in the basal regions. Transbronchial biopsy confirmed the diagnosis. PMID:24174699

  5. Tobacco smoke and the pulmonary alveolar macrophage.

    PubMed

    Drath, D B; Davies, P; Karnovsky, M L; Huber, G L

    1979-01-01

    Our results indicate that tobacco smoke exposure to varying duration causes morphological, biochemical and functional alterations in pulmonary alveolar macrophages. The results of these changes is a population of alveolar macrophages made up of larger cells, with a reduced nucleus-cytoplasmic ratio, which are heavily loaded with heterolysosomes containing lipid. Though their fractional complement of mitochondria remains the same, an increase in the inner mitochondrial membrane surface area may be related to an enhanced oxidative metabolism. The cell is biochemically activated particularly following chronic exposure and is functionally impaired with respect to phagocytosis. PMID:232822

  6. Lung Transplant Recipient with Pulmonary Alveolar Proteinosis

    PubMed Central

    Hahn, M. Frances; Abdelrazek, Hesham; Patel, Vipul J.; Walia, Rajat

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a progressive lung disease characterized by accumulated surfactant-like lipoproteinaceous material in the alveoli and distal bronchioles. This accumulation is the result of impaired clearance by alveolar macrophages. PAP has been described in 11 solid organ transplant recipients, 9 of whom were treated with mammalian target of rapamycin inhibitors. We report a case of a lung transplant recipient treated with prednisone, mycophenolate mofetil (MMF), and tacrolimus who ultimately developed PAP, which worsened when MMF was replaced with everolimus. PMID:27213073

  7. Characterization of the porcine p65 subunit of NF-κB and its association with virus antibody levels.

    PubMed

    Li, Hegang; Ma, Guojian; Gui, Duan; Zhao, Shuanping; Wang, Pan; He, Kongwang; Wang, Xuemin; Ruan, Jinxue; Cao, Jiyue; Yang, Shulin; Li, Kui

    2011-03-01

    NF-κB p65 subunit plays important roles in controlling both innate and adaptive immunity. Here we report the characterization of porcine NF-κB p65 subunit (pp65). pp65 shows high similarity to other mammalian counterparts. pp65 mRNA expression was mainly observed in lung, spleen, liver and small intestine. Furthermore, overexpression of pp65 activates NF-κB in porcine endothelial cell line PIEC, porcine alveolar macrophages cell line 3D4/21 and porcine primary fetal fibroblasts. A COOH-terminal truncation derivative of pp65 (pp65RHD) has been identified as a specific transdominant inhibitor of NFκB. Association study was performed on the selected SNP and indel. The results revealed that the SNP BglI was significantly associated (P<0.05) with pig reproduction and respiratory syndrome virus antibody level (PRRSV-AB) (0 day and 17 days), the classical swine fever virus (CSFV) antibody blocking rates (CSFV-AB) (0 day and 17 days) and pseudorabies virus antibody level (PRV-AB) (0 day and 32 days). PMID:21269694

  8. Secondary Alveolar Bone Grafting and Iliac Cancellous Bone Harvesting for Patients With Alveolar Cleft.

    PubMed

    Pan, Weiyi; Wu, Chenzhou; Yang, Zheng; Duan, Zexi; Su, Zhifei; Wang, Peiqi; Zheng, Qian; Li, Chunjie

    2016-06-01

    To assess the efficacy of present interventions optimizing the result of secondary alveolar bone grafting (SABG) and the interventions alleviating the donor site morbidity after iliac cancellous bone harvesting. Researches were identified by searching the electronic database of MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, Chinese BioMedical Literature Database, and the China National Knowledge Infrastructure. In addition, relevant journals and references of the included studies were searched manually. The Oxford 2011 Levels of Evidence were applied to assess the methodological quality of selected studies, and the best evidence synthesis system was applied afterward to measure the strength of evidence. As a result, 42 studies were considered eligible and included, among which 4 were of high quality while 38 were of low quality. Thirty lines of evidences were acquired after the synthesis, among which 13 were rated as moderate while 17 were rated as insufficient. As for the interventions optimizing the result of SABG, moderate evidence confirmed the efficacy of preoperative orthodontic treatment, the superiority of performing SABG before the eruption of canine, and the accuracy of cone beam computed tomography in preoperative estimation of the cleft volume. As for the interventions alleviating the morbidity of iliac cancellous bone harvesting, moderate evidence confirmed the treatment benefit of the interventions below: minimally invasive technique, including trephine and Shepard osteotomy; preemptive analgesia, including continuous bupivacaine infusion or transversus abdominis plane block. As for the rest interventions, only insufficient evidence was found. PMID:27244214

  9. Mechanical characterization of porcine corneas.

    PubMed

    Boschetti, F; Triacca, V; Spinelli, L; Pandolfi, A

    2012-03-01

    An experimental program has been carried out in order to investigate the mechanical behavior of porcine corneas. We report the results of inflation tests on the whole cornea and uniaxial tests on excised corneal strips, performed on 51 fresh porcine eyes. Uniaxial tests have been performed on specimens cut from previously inflated corneas. The cornea behavior is characterized by means of elastic stiffness, measured on both average pressure-apex displacement and average uniaxial stress-strain curves; and by means of transversal contraction coefficient, peak stress, and failure stress measured on uniaxial stress-strain curves. Uniaxial tests performed on excised strips allowed to measure the anisotropy in the corneal stiffness and to compare the stiffness of the cornea with the one of the sclera. Viscous properties of the cornea have been obtained through uniaxial relaxation curves on excised corneal strips. The relevant geometrical parameters have been measured and, with the aid of the elastic thin shell theory, a stress-strain curve has been derived from the average inflation test data and compared with similar data available in the literature. The experimental system has been developed in view of future applications to the mechanical testing of both porcine and human corneas. PMID:22482683

  10. Alveolar mechanics using realistic acinar models

    NASA Astrophysics Data System (ADS)

    Kumar, Haribalan; Lin, Ching-Long; Tawhai, Merryn H.; Hoffman, Eric A.

    2009-11-01

    Accurate modeling of the mechanics in terminal airspaces of the lung is desirable for study of particle transport and pathology. The flow in the acinar region is traditionally studied by employing prescribed boundary conditions to represent rhythmic breathing and volumetric expansion. Conventional models utilize simplified spherical or polygonal units to represent the alveolar duct and sac. Accurate prediction of flow and transport characteristics may require geometries reconstructed from CT-based images and serve to understand the importance of physiologically realistic representation of the acinus. In this effort, we present a stabilized finite element framework, supplemented with appropriate boundary conditions at the alveolar mouth and septal borders for simulation of the alveolar mechanics and the resulting airflow. Results of material advection based on Lagrangian tracking are presented to complete the study of transport and compare the results with simplified acinar models. The current formulation provides improved understanding and realization of a dynamic framework for parenchymal mechanics with incorporation of alveolar pressure and traction stresses.

  11. Teaching Alveolar Ventilation with Simple, Inexpensive Models

    ERIC Educational Resources Information Center

    DiCarlo, Stephen E.

    2008-01-01

    When teaching and learning about alveolar ventilation with our class of 300 first-year medical students, we use four simple, inexpensive "models." The models, which encourage research-oriented learning and help our students to understand complex ideas, are distributed to the students before class. The students anticipate something new every day,…

  12. Selective alveolar corticotomy to intrude overerupted molars.

    PubMed

    Oliveira, Dauro Douglas; de Oliveira, Bruno Franco; de Araújo Brito, Helio Henrique; de Souza, Margareth Maria Gomes; Medeiros, Paulo José

    2008-06-01

    Orthodontic intrusion of overerupted molars in adults is challenging for most clinicians. Efficient intrusion can be achieved by combining selective alveolar corticotomies with a modified full-coverage maxillary splint to reduce surgical risks, treatment time, and costs for both orthodontists and patients. PMID:18538256

  13. Alveolar proteinosis associated with aluminium dust inhalation.

    PubMed

    Chew, R; Nigam, S; Sivakumaran, P

    2016-08-01

    Secondary alveolar proteinosis is a rare lung disease which may be triggered by a variety of inhaled particles. The diagnosis is made by detection of anti-granulocyte-macrophage colony-stimulating factor antibodies in bronchoalveolar lavage fluid, which appears milky white and contains lamellar bodies. Aluminium has been suggested as a possible cause, but there is little evidence in the literature to support this assertion. We report the case of a 46-year-old former boilermaker and boat builder who developed secondary alveolar proteinosis following sustained heavy aluminium exposure. The presence of aluminium was confirmed both by histological examination and metallurgical analysis of a mediastinal lymph node. Despite cessation of exposure to aluminium and treatment with whole-lung lavage which normally results in improvements in both symptoms and lung function, the outcome was poor and novel therapies are now being used for this patient. It may be that the natural history in aluminium-related alveolar proteinosis is different, with the metal playing a mediating role in the disease process. Our case further supports the link between aluminium and secondary alveolar proteinosis and highlights the need for measures to prevent excessive aluminium inhalation in relevant industries. PMID:27099254

  14. Mechanical ventilation causes pulmonary mitochondrial dysfunction and delayed alveolarization in neonatal mice.

    PubMed

    Ratner, Veniamin; Sosunov, Sergey A; Niatsetskaya, Zoya V; Utkina-Sosunova, Irina V; Ten, Vadim S

    2013-12-01

    Hyperoxia inhibits pulmonary bioenergetics, causing delayed alveolarization in mice. We hypothesized that mechanical ventilation (MV) also causes a failure of bioenergetics to support alveolarization. To test this hypothesis, neonatal mice were ventilated with room air for 8 hours (prolonged) or for 2 hours (brief) with 15 μl/g (aggressive) tidal volume (Tv), or for 8 hours with 8 μl/g (gentle) Tv. After 24 hours or 10 days of recovery, lung mitochondria were examined for adenosine diphosphate (ADP)-phosphorylating respiration, using complex I (C-I)-dependent, complex II (C-II)-dependent, or cytochrome C oxidase (C-IV)-dependent substrates, ATP production rate, and the activity of C-I and C-II. A separate cohort of mice was exposed to 2,4-dinitrophenol (DNP), a known uncoupler of oxidative phosphorylation. At 10 days of recovery, pulmonary alveolarization and the expression of vascular endothelial growth factor (VEGF) were assessed. Sham-operated littermates were used as control mice. At 24 hours after aggressive MV, mitochondrial ATP production rates and the activity of C-I and C-II were significantly decreased compared with control mice. However, at 10 days of recovery, only mice exposed to prolonged-aggressive MV continued to exhibit significantly depressed mitochondrial respiration. This was associated with significantly poorer alveolarization and VEGF expression. In contrast, mice exposed to brief-aggressive or prolonged-gentle MV exhibited restored mitochondrial ADP-phosphorylation, normal alveolarization and pulmonary VEGF content. Exposure to DNP fully replicated the phenotype consistent with alveolar developmental arrest. Our data suggest that the failure of bioenergetics to support normal lung development caused by aggressive and prolonged ventilation should be considered a fundamental mechanism for the development of bronchopulmonary dysplasia in premature neonates. PMID:23980609

  15. Secondary pulmonary alveolar proteinosis in hematologic malignancies.

    PubMed

    Chaulagain, Chakra P; Pilichowska, Monika; Brinckerhoff, Laurence; Tabba, Maher; Erban, John K

    2014-12-01

    Pulmonary alveolar proteinosis (PAP), characterized by deposition of intra-alveolar PAS positive protein and lipid rich material, is a rare cause of progressive respiratory failure first described by Rosen et al. in 1958. The intra-alveolar lipoproteinaceous material was subsequently proven to have been derived from pulmonary surfactant in 1980 by Singh et al. Levinson et al. also reported in 1958 the case of 19-year-old female with panmyelosis afflicted with a diffuse pulmonary disease characterized by filling of the alveoli with amorphous material described as "intra-alveolar coagulum". This is probably the first reported case of PAP in relation to hematologic malignancy. Much progress has been made on PAP first described by Rosen which is currently classified as idiopathic or primary or autoimmune PAP. Idiopathic PAP occurs as a result of auto-antibodies directed against granulocyte-macrophage colony stimulating factor (GM-CSF) impeding the surfactant clearing function of alveolar macrophages leading to progressive respiratory failure. Whole lung lavage and GM-CSF therapy has improved outcomes in patients with idiopathic PAP. Despite major advancement in the management of hematologic malignancy and its complications, little is known about the type of PAP first described by Levinson and now known as secondary PAP; a term also used when PAP occurs due to other causes such as occupational dusts. In this article we review and analyze the limited literature available in secondary PAP due to hematologic malignancies and present a case of PAP associated with chronic lymphocytic leukemia successfully treated with bendamustine and rituximab. PMID:25300566

  16. 7 CFR 1230.18 - Porcine animal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Porcine animal. 1230.18 Section 1230.18 Agriculture... animal. Porcine animal means a swine, that is raised as (a) a feeder pig, that is, a young pig sold to another person to be finished for slaughtering over a period of more than 1 month; (b) for...

  17. 7 CFR 1230.18 - Porcine animal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Porcine animal. 1230.18 Section 1230.18 Agriculture... animal. Porcine animal means a swine, that is raised as (a) a feeder pig, that is, a young pig sold to another person to be finished for slaughtering over a period of more than 1 month; (b) for...

  18. Technical note: Isolation and characterization of porcine mammary epithelial cells.

    PubMed

    Dahanayaka, S; Rezaei, R; Porter, W W; Johnson, G A; Burghardt, R C; Bazer, F W; Hou, Y Q; Wu, Z L; Wu, G

    2015-11-01

    Within the mammary gland, functional synthesis of milk is performed by its epithelial (alveolar) cells. The availability of a stable mammary epithelial cell line is essential for biochemical studies to elucidate cellular and molecular mechanisms responsible for nutritional regulation of lactation. Therefore, porcine mammary epithelial cells (PMEC) were isolated from mammary glands of a 9-mo-old nonpregnant and nonlactating gilt and cultured to establish a nonimmortalized cell line. These cells were characterized by expression of cytokeratin-18 (an intermediate filament specific for epithelial cells), β-casein (a specific marker for mammary epithelial cells), and α-lactalbumin. In culture, the PMEC doubled in number every 24 h and maintained a cobblestone morphology, typical for cultured epithelial cells, for at least 15 passages. Addition of 0.2 to 2 μg/mL prolactin to culture medium for 3 d induced the production of β-casein and α-lactalbumin by PMEC in a dose-dependent manner. Thus, we have successfully developed a useful PMEC line for future studies of cellular and molecular regulation of milk synthesis by mammary epithelial cells of the sow. PMID:26641038

  19. Differences in immune response of pigs challenged with a high versus low dose inoculum of porcine reproductive and respiratory syndrome virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Porcine reproductive and respiratory syndrome virus (PRRSV) continues to be an economically important infectious disease of swine. Mechanisms governing activation of the innate immune response to PRRSV remain to be elucidated. Virulence differences observed between PRRSV isolates have been attribu...

  20. Genome sequences and phylogenetic analysis of K88- and F18-positive porcine enterotoxigenic Escherichia coli.

    PubMed

    Shepard, Sara M; Danzeisen, Jessica L; Isaacson, Richard E; Seemann, Torsten; Achtman, Mark; Johnson, Timothy J

    2012-01-01

    Porcine enterotoxigenic Escherichia coli (ETEC) continues to result in major morbidity and mortality in the swine industry via postweaning diarrhea. The key virulence factors of ETEC strains, their serotypes, and their fimbrial components have been well studied. However, most studies to date have focused on plasmid-encoded traits related to colonization and toxin production, and the chromosomal backgrounds of these strains have been largely understudied. Here, we generated the genomic sequences of K88-positive and F18-positive porcine ETEC strains and examined the phylogenetic distribution of clinical porcine ETEC strains and their plasmid-associated genetic content. The genomes of porcine ETEC strains UMNK88 and UMNF18 were both found to contain remarkable plasmid complements containing known virulence factors, potential novel virulence factors, and antimicrobial resistance-associated elements. The chromosomes of these strains also possessed several unique genomic islands containing hypothetical genes with similarity to classical virulence factors, although phage-associated genomic islands dominated the accessory genomes of these strains. Phylogenetic analysis of 78 clinical isolates associated with neonatal and porcine diarrhea revealed that a limited subset of porcine ETEC lineages exist that generally contain common toxin and fimbrial profiles, with many of the isolates belonging to the ST10, ST23, and ST169 multilocus sequencing types. These lineages were generally distinct from existing human ETEC database isolates. Overall, most porcine ETEC strains appear to have emerged from a limited subset of E. coli lineages that either have an increased propensity to carry plasmid-encoded virulence factors or have the appropriate ETEC core genome required for virulence. PMID:22081385

  1. Pelvic alveolar rhabdomyosarcoma in a young adult

    PubMed Central

    Reisner, David; Amadi, Chiemezie; Beckman, Irwin; Patel, Shweta; Surampudi, Ramana

    2015-01-01

    Rhabdomyosarcomas are soft-tissue tumors, rare in adults. Accounting for nearly 5% of childhood cancers, they represent less than 0.03% of adult malignancies (1, 2). Three different subtypes of rhabdomyosarcoma have been described (embryonal, alveolar and pleomorphic), making up approximately 50%, 30%, and 20% of the cases, respectively (3). Although the definitive diagnosis is made pathologically, some distinguishing features among these subtypes, and between rhabdomyosarcomas and other soft-tissue tumors, can be suggested on MRI and CT. We present an interesting case of a 20-year-old female with a locally aggressive pelvic alveolar rhabdomyosarcoma. While the prognosis has improved with newer treatment techniques, overall survival rates remain poor. Our case study presents typical features of a rare disease, which can often present a diagnostic dilemma for clinicians.

  2. Bilateral stony lung: pulmonary alveolar microlithiasis.

    PubMed

    Chandra, Subhash; Mohan, Anant; Guleria, Randeep; Das, Prasenjit; Sarkar, Chitra

    2009-01-01

    A 40-year-old male paddy field worker was referred for exertional shortness of breath and non-productive cough for 4 years. He had been treated for pulmonary tuberculosis twice. Chest radiograph showed extensive bilateral nodular opacities ("sandstorm-like") in the middle and lower lobe. Pulmonary function tests revealed a restrictive ventilatory defect. High resolution CT showed widespread nodular infiltration with "crazy paving" appearance and interrupted black pleura sign. This was confirmed as pulmonary alveolar microlithiasis (PAM) by trans-bronchial lung biopsy, which showed normal respiratory lining epithelium with dilated alveolar spaces containing many calcific bodies, some of which showed concentric calcification. The possibilities of silicosis (due to exposure to husk) and tuberculosis, both of which can mimic PAM clinically and radiologically, made this case a diagnostic challenge. PMID:21686505

  3. Bilateral stony lung: pulmonary alveolar microlithiasis

    PubMed Central

    Chandra, Subhash; Mohan, Anant; Guleria, Randeep; Das, Prasenjit; Sarkar, Chitra

    2009-01-01

    A 40-year-old male paddy field worker was referred for exertional shortness of breath and non-productive cough for 4 years. He had been treated for pulmonary tuberculosis twice. Chest radiograph showed extensive bilateral nodular opacities (“sandstorm-like”) in the middle and lower lobe. Pulmonary function tests revealed a restrictive ventilatory defect. High resolution CT showed widespread nodular infiltration with “crazy paving” appearance and interrupted black pleura sign. This was confirmed as pulmonary alveolar microlithiasis (PAM) by trans-bronchial lung biopsy, which showed normal respiratory lining epithelium with dilated alveolar spaces containing many calcific bodies, some of which showed concentric calcification. The possibilities of silicosis (due to exposure to husk) and tuberculosis, both of which can mimic PAM clinically and radiologically, made this case a diagnostic challenge. PMID:21686505

  4. Treatment of Adult Primary Alveolar Proteinosis.

    PubMed

    Rodríguez Portal, José Antonio

    2015-07-01

    Pulmonary alveolar proteinosis (PAP) is a rare disease characterized by the accumulation of surfactant-like lipoproteinaceous material in the distal air spaces and terminal bronchi, which may lead to impaired gas exchange. This accumulation of surfactant is due to decreased clearance by the alveolar macrophages. Its primary, most common form, is currently considered an autoimmune disease. Better knowledge of the causes of PAP have led to the emergence of alternatives to whole lung lavage, although this is still considered the treatment of choice. Most studies are case series, often with limited patient numbers, so the level of evidence is low. Since the severity of presentation and clinical course are variable, not all patients will require treatment. Due to the low level of evidence, some objective criteria based on expert opinion have been arbitrarily proposed in an attempt to define in which patients it is best to initiate treatment. PMID:25896950

  5. [Pulmonary alveolar proteinosis - a case report].

    PubMed

    Johannesdottir, Ragnheidur M; Jonsson, Steinn; Valsson, Felix; Hardardottir, Hronn; Amundadottir, Olof R; Bjornsson, Eythor; Nikulasson, Sigfus; Gudbjartsson, Tomas

    2014-11-01

    Pulmonary alveolar proteinosis (PAP) is a rare lung disease of unknown origin, where an amorphous lipoprotein material accumulates in the alveoli of the lungs. We describe a young male with a four month history of progressive dyspnea, low grade fever, hypoxemia and weight loss. Chest X-ray showed diffuse interstitial and alveolar infiltrates in both lungs. The diagnosis of PAP was confirmed with trans-bronchial lung biopsy. Because of a deteriorating clinical course a whole lung lavage was performed. Under general anesthesia, both lungs were lavaged with warm saline in two different sessions with good results. Two years later the patient is almost free of symptoms and lung function has markedly improved. PMID:25413889

  6. Rare lung diseases II: Pulmonary alveolar proteinosis

    PubMed Central

    Juvet, Stephen C; Hwang, David; Waddell, Thomas K; Downey, Gregory P

    2008-01-01

    The present article is the second in a series on rare lung diseases. It focuses on pulmonary alveolar proteinosis (PAP), a disorder in which lipoproteinaceous material accumulates in the alveolar space. PAP was first described in 1958, and for many years the nature of the material accumulating in the lungs was unknown. Major insights into PAP have been made in the past decade, and these have led to the notion that PAP is an autoimmume disorder in which autoantibodies interfere with signalling through the granulocyte-macrophage colony-stimulating factor receptor, leading to macrophage and neutrophil dysfunction. This has spurred new therapeutic approaches to this disorder. The discussion of PAP will begin with a case report, then will highlight the classification of PAP and review recent insights into the pathogenesis of PAP. The approach to therapy and the prognosis of PAP will also be discussed. PMID:18551202

  7. Depletion of Alveolar Macrophages Does Not Prevent Hantavirus Disease Pathogenesis in Golden Syrian Hamsters

    PubMed Central

    Hammerbeck, Christopher D.; Brocato, Rebecca L.; Bell, Todd M.; Schellhase, Christopher W.; Mraz, Steven R.; Queen, Laurie A.

    2016-01-01

    ABSTRACT Andes virus (ANDV) is associated with a lethal vascular leak syndrome in humans termed hantavirus pulmonary syndrome (HPS). The mechanism for the massive vascular leakage associated with HPS is poorly understood; however, dysregulation of components of the immune response is often suggested as a possible cause. Alveolar macrophages are found in the alveoli of the lung and represent the first line of defense to many airborne pathogens. To determine whether alveolar macrophages play a role in HPS pathogenesis, alveolar macrophages were depleted in an adult rodent model of HPS that closely resembles human HPS. Syrian hamsters were treated, intratracheally, with clodronate-encapsulated liposomes or control liposomes and were then challenged with ANDV. Treatment with clodronate-encapsulated liposomes resulted in significant reduction in alveolar macrophages, but depletion did not prevent pathogenesis or prolong disease. Depletion also did not significantly reduce the amount of virus in the lung of ANDV-infected hamsters but altered neutrophil recruitment, MIP-1α and MIP-2 chemokine expression, and vascular endothelial growth factor (VEGF) levels in hamster bronchoalveolar lavage (BAL) fluid early after intranasal challenge. These data demonstrate that alveolar macrophages may play a limited protective role early after exposure to aerosolized ANDV but do not directly contribute to hantavirus disease pathogenesis in the hamster model of HPS. IMPORTANCE Hantaviruses continue to cause disease worldwide for which there are no FDA-licensed vaccines, effective postexposure prophylactics, or therapeutics. Much of this can be attributed to a poor understanding of the mechanism of hantavirus disease pathogenesis. Hantavirus disease has long been considered an immune-mediated disease; however, by directly manipulating the Syrian hamster model, we continue to eliminate individual immune cell types. As the most numerous immune cells present in the respiratory tract

  8. Alveolar vertical distraction osteogenesis: historical and biologic review and case presentation.

    PubMed

    Emtiaz, Shahram; Noroozi, Sohrab; Caramês, João; Fonseca, Luís

    2006-12-01

    Dental rehabilitation of partially or totally edentulous patients with dental implants has become common practice in the last few decades, with reliable long-term results. However, local conditions of edentulous alveolar ridges may be unfavorable for implant placement. Vertically deficient alveolar ridges, in particular, may have insufficient bone volume to hold implants of adequate dimensions, making implant placement difficult or impossible. To correct this situation, a variety of surgical procedures have been proposed, including onlay bone grafts, vertical guided bone regeneration, and alveolar distraction osteogenesis. Distraction osteogenesis is a biologic process of new bone formation between the surfaces of bone segments that are gradually separated by incremental traction. This process is initiated when a traction force is applied to the bone segments and continues as long as the callus tissues are stretched. This traction force, in turn, generates tension within the tissues that connect the bone segments, which stimulates new bone formation parallel to the vector of distraction. The aim of this article is to provide clinicians with the historical background of and biologic basis for the concept of distraction osteogenesis, which can be traced back to the 1800s. Finally, a clinical case is presented to demonstrate a step-by-step application of alveolar distraction osteogenesis as a treatment protocol in a partially edentulous ridge for improvement of esthetics. PMID:17243326

  9. Alveolar flows of the developing lungs:from embryonic to early childhood airways

    NASA Astrophysics Data System (ADS)

    Tenenbaum-Katan, Janna; Hofemeier, Philipp; Fishler, Rami; Rothen-Rutishauser, Barbara; Sznitman, Josue

    2014-11-01

    At the onset of life in utero the respiratory system is simply a liquid-filled duct. With our first breath, alveoli are filled with air and become a significant port of entry for airborne particles. As such, alveolar lining is nearly fully functional at birth, though lung development continues during childhood as structural changes increase alveolar surface area to optimize ventilation. We hypothesize that such fluid dynamical changes potentially affect two phenomena occurring within alveoli: (i) flow patterns in airspaces at distinct stages of both in- and ex-utero life and (ii) fate of inhaled particles ex-utero. To investigate these phenomena, we combine experimental and numerical approaches where (i) microfluidic in vitro devices mimic liquid flows across the epithelium of fetal airspaces, and (ii) computational simulations are employed to examine particle transport and deposition in the deep alveolated regions of infants' lungs. Our approaches capture anatomically-inspired geometries based on morphometrical data, as well as physiological flows, including the convective-diffusive nature of submicron particle transport in alveolar regions.Overall, we investigate respiratory flows in alveolar regions of developing lungs, from early embryonic stages to late childhood

  10. 7 CFR 1230.608 - Imported porcine animals, pork, and pork products.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false Imported porcine animals, pork, and pork products. 1230.608 Section 1230.608 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND...

  11. 7 CFR 1230.608 - Imported porcine animals, pork, and pork products.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 10 2011-01-01 2011-01-01 false Imported porcine animals, pork, and pork products. 1230.608 Section 1230.608 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND...

  12. 7 CFR 1230.111 - Remittance of assessments on domestic porcine animals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Remittance of assessments on domestic porcine animals. 1230.111 Section 1230.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH,...

  13. 7 CFR 1230.608 - Imported porcine animals, pork, and pork products.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Imported porcine animals, pork, and pork products. 1230.608 Section 1230.608 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND...

  14. 7 CFR 1230.111 - Remittance of assessments on domestic porcine animals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false Remittance of assessments on domestic porcine animals. 1230.111 Section 1230.111 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH,...

  15. 7 CFR 1230.608 - Imported porcine animals, pork, and pork products.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false Imported porcine animals, pork, and pork products. 1230.608 Section 1230.608 Agriculture Regulations of the Department of Agriculture (Continued) AGRICULTURAL MARKETING SERVICE (MARKETING AGREEMENTS AND ORDERS; MISCELLANEOUS COMMODITIES), DEPARTMENT OF AGRICULTURE PORK PROMOTION, RESEARCH, AND...

  16. Pulmonary alveolar proteinosis: time to shift?

    PubMed

    Papiris, Spyros A; Tsirigotis, Panagiotis; Kolilekas, Likurgos; Papadaki, Georgia; Papaioannou, Andriana I; Triantafillidou, Christina; Papaporfyriou, Anastasia; Karakatsani, Anna; Kagouridis, Konstantinos; Griese, Matthias; Manali, Effrosyni D

    2015-06-01

    Pulmonary alveolar proteinosis (PAP) is categorized into hereditary, secondary and autoimmune PAP (aPAP) types. The common pathogenesis is the ability of the alveolar macrophages to catabolize phagocytized surfactant is affected. Hereditary PAP is caused by mutations involving the GM-CSF signaling, particularly in genes for the GM-CSF receptor and sometimes by GATA2 mutations. Secondary PAP occurs in hematologic malignancies, other hematologic disorders, miscellaneous malignancies, fume and dust inhalation, drugs, autoimmune disorders and immunodeficiencies. aPAP is related to the production of GM-CSF autoantibodies. PAP is characterized morphologically by the inappropriate and progressive 'occupation' of the alveolar spaces by an excessive amount of unprocessed surfactant, limiting gas exchange and gradually exhausting the respiratory reserve. Myeloid cells' immunity deteriorates, increasing the risk of infections. Treatment of PAP is based on its etiology. In aPAP, recent therapeutic advances might shift the treatment option from the whole lung lavage procedure under general anesthesia to the inhalation of GM-CSF 'as needed'. PMID:25864717

  17. In situ methods for assessing alveolar mechanics.

    PubMed

    Wu, You; Perlman, Carrie E

    2012-02-01

    Lung mechanics are an important determinant of physiological and pathophysiological lung function. Recent light microscopy studies of the intact lung have furthered the understanding of lung mechanics but used methodologies that may have introduced artifacts. To address this concern, we employed a short working distance water immersion objective to capture confocal images of a fluorescently labeled alveolar field on the costal surface of the isolated, perfused rat lung. Surface tension held a saline drop between the objective tip and the lung surface, such that the lung surface was unconstrained. For comparison, we also imaged with O-ring and coverslip; with O-ring, coverslip, and vacuum pressure; and without perfusion. Under each condition, we ventilated the lung and imaged the same region at the endpoints of ventilation. We found use of a coverslip caused a minimal enlargement of the alveolar field; additional use of vacuum pressure caused no further dimensional change; and absence of perfusion did not affect alveolar field dimension. Inflation-induced expansion was unaltered by methodology. In response to inflation, percent expansion was the same as recorded by all four alternative methods. PMID:22074721

  18. A porcine model of osteosarcoma

    PubMed Central

    Saalfrank, A; Janssen, K-P; Ravon, M; Flisikowski, K; Eser, S; Steiger, K; Flisikowska, T; Müller-Fliedner, P; Schulze, É; Brönner, C; Gnann, A; Kappe, E; Böhm, B; Schade, B; Certa, U; Saur, D; Esposito, I; Kind, A; Schnieke, A

    2016-01-01

    We previously produced pigs with a latent oncogenic TP53 mutation. Humans with TP53 germline mutations are predisposed to a wide spectrum of early-onset cancers, predominantly breast, brain, adrenal gland cancer, soft tissue sarcomas and osteosarcomas. Loss of p53 function has been observed in >50% of human cancers. Here we demonstrate that porcine mesenchymal stem cells (MSCs) convert to a transformed phenotype after activation of latent oncogenic TP53R167H and KRASG12D, and overexpression of MYC promotes tumorigenesis. The process mimics key molecular aspects of human sarcomagenesis. Transformed porcine MSCs exhibit genomic instability, with complex karyotypes, and develop into sarcomas on transplantation into immune-deficient mice. In pigs, heterozygous knockout of TP53 was sufficient for spontaneous osteosarcoma development in older animals, whereas homozygous TP53 knockout resulted in multiple large osteosarcomas in 7–8-month-old animals. This is the first report that engineered mutation of an endogenous tumour-suppressor gene leads to invasive cancer in pigs. Unlike in Trp53 mutant mice, osteosarcoma developed in the long bones and skull, closely recapitulating the human disease. These animals thus promise a model for juvenile osteosarcoma, a relatively uncommon but devastating disease. PMID:26974205

  19. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells.

    PubMed

    Sweeney, Sinbad; Theodorou, Ioannis G; Zambianchi, Marta; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng Jim; Chung, Kian Fan; Shaffer, Milo S P; Ryan, Mary P; Porter, Alexandra E; Tetley, Teresa D

    2015-06-21

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit. PMID:25996248

  20. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    PubMed Central

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Martina; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-01-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit. PMID:25996248

  1. [Alveolar hemorrhage associated with intestinal inflammatory disease and Hashimoto thyroiditis].

    PubMed

    Rabec, C; Barcat, J; Rey, D

    2003-06-01

    Diffuse alveolar hemorrhage (DAH) is characterized by diffuse bleeding into alveolar spaces. Three histopathological patterns may be seen: 1) pulmonary capillaritis due to immunological aggression to the membrane, 2) diffuse alveolar damage within the context of acute respiratory distress syndrome, and 3) and "bland" DAH without alveolar or capillary damage. In the first two groups, pulmonary damage usually occurs within the context of a systemic disease. In the last, injury is usually found only in the lung, an entity called pulmonary hemosiderosis. We present a case of DAH with neither capillaritis nor diffuse alveolar damage in association with inflammatory bowel disease and Hashimoto thyroiditis. The case is interesting both because the association has not yet been described in the literature and because the presence of alveolar bleeding without evident tissue damage within the context of known autoimmune diseases may extend the field to include a new pathophysiological mechanism of pulmonary hemorrhage. PMID:12797945

  2. Candidates Cell Sources to Regenerate Alveolar Bone from Oral Tissue

    PubMed Central

    Nishimura, Masahiro; Takase, Kazuma; Suehiro, Fumio; Murata, Hiroshi

    2012-01-01

    Most of the cases of dental implant surgery, especially the bone defect extensively, are essential for alveolar ridge augmentation. As known as cell therapy exerts valuable effects on bone regeneration, numerous reports using various cells from body to regenerate bone have been published, including clinical reports. Mesenchymal cells that have osteogenic activity and have potential to be harvested from intra oral site might be a candidate cells to regenerate alveolar bone, even dentists have not been harvested the cells outside of mouth. This paper presents a summary of somatic cells in edentulous tissues which could subserve alveolar bone regeneration. The candidate tissues that might have differentiation potential as mesenchymal cells for bone regeneration are alveolar bone chip, bone marrow from alveolar bone, periosteal tissue, and gingival tissue. Understanding their phenotype consecutively will provide a rational approach for alveolar ridge augmentation. PMID:22505911

  3. Recent advances in alveolar biology: some new looks at the alveolar interface.

    PubMed

    Possmayer, Fred; Hall, Stephen B; Haller, Thomas; Petersen, Nils O; Zuo, Yi Y; Bernardino de la Serna, Jorge; Postle, Anthony D; Veldhuizen, Ruud A W; Orgeig, Sandra

    2010-08-31

    This article examines the manner in which some new methodologies and novel concepts have contributed to our understanding of how pulmonary surfactant reduces alveolar surface tension. Investigations utilizing small angle X-ray diffraction, inverted interface fluorescence microscopy, time of flight-secondary ion mass spectroscopy, atomic force microscopy, two-photon fluorescence microscopy and electrospray mass spectroscopy are highlighted and a new model of ventilation-induced acute lung injury described. This contribution attempts to emphasize how these new approaches have resulted in a fuller appreciation of events presumably occurring at the alveolar interface. PMID:20206718

  4. Autophagy sustains the replication of porcine reproductive and respiratory virus in host cells

    SciTech Connect

    Liu, Qinghao; Qin, Yixian; Zhou, Lei; Kou, Qiuwen; Guo, Xin; Ge, Xinna; Yang, Hanchun; Hu, Hongbo

    2012-08-01

    In this study, we confirmed the autophagy induced by porcine reproductive and respiratory syndrome virus (PRRSV) in permissive cells and investigated the role of autophagy in the replication of PRRSV. We first demonstrated that PRRSV infection significantly results in the increased double-membrane vesicles, the accumulation of LC3 fluorescence puncta, and the raised ratio of LC3-II/{beta}-actin, in MARC-145 cells. Then we discovered that induction of autophagy by rapamycin significantly enhances the viral titers of PRRSV, while inhibition of autophagy by 3-MA and silencing of LC3 gene by siRNA reduces the yield of PRRSV. The results showed functional autolysosomes can be formed after PRRSV infection and the autophagosome-lysosome-fusion inhibitor decreases the virus titers. We also examined the induction of autophagy by PRRSV infection in pulmonary alveolar macrophages. These findings indicate that autophagy induced by PRRSV infection plays a role in sustaining the replication of PRRSV in host cells.

  5. Isolation and Culture of Human Alveolar Type II Pneumocytes.

    PubMed

    Witherden, I R; Tetley, T D

    2001-01-01

    Alveolar type II pneumocytes (alveolar type II cells; TII cells) play an important role in the homeostasis of the alveolar unit. They are the progenitor cells to the type I pneumocyte and are therefore responsible for regeneration of alveolar epithelium following alveolar epithelial cell damage. The type I cell covers over 90% of the alveolar surface, reflecting its capacity to stretch into a flattened cell with very little depth (approx. 0.1 µm), but with a large surface area, to facilitate gas exchange. Nevertheless, the type II cell outnumbers type I cells, estimated to be by 2:1 in rodents. Most of the type II cell lies buried in the interstitium of the alveolus, with only the apical tip of the cell reaching into the airspace, through which another crucial function, provision of alveolar surfactant, occurs. Surfactant synthesis and secretion is a unique feature of type II cells; surfactant consists of a high proportion of phospholipids (approx. 90%) and a small proportion of protein (approx. 10%), which contains surfactant apoprotein (SP), of which four have so far been described, SP-A, SP-B, SP-C, and SP-D (1,2). Surfactant is highly surface active and is essential to prevent alveolar collapse. In addition, surfactant has many other roles, including pulmonary host defense. Compromised surfactant synthesis and function are believed to be a feature of numerous disease states (1,2), including infant respiratory distress syndrome, adult respiratory distress syndrome, alveolar proteinosis, and microbial infection. PMID:21336897

  6. Porcine deltacoronavirus: histological lesions and genetic characterization.

    PubMed

    Wang, Leyi; Hayes, Jeff; Sarver, Craig; Byrum, Beverly; Zhang, Yan

    2016-01-01

    First identified in 2012 in a surveillance study in Hong Kong, porcine deltacoronavirus (PDCoV) is a proposed member of the genus Deltacoronavirus of the family Coronaviridae. In February of 2014, PDCoV was detected in pigs with clinical diarrheal symptoms for the first time in the USA. Since then, it has been detected in more than 20 states in the USA and in other countries, including Canada, South Korea, and mainland China. So far, histological lesions in the intestines of pigs naturally infected with PDCoV under field conditions have not been reported. In this report, we describe the characteristic histological lesions in the small intestine that were associated with PDCoV infection, as evidenced by detection of viral nucleic acid by RT-PCR. In addition, we performed genomic analysis to determine the genetic relationship of all PDCoV strains from the four countries. We found that PDCoV mainly caused histological lesions in the small intestines of naturally infected piglets. Sequence analysis demonstrated that the PDCoV strains of different countries are closely related and shared high nucleotide sequence similarity; however, deletion patterns in the spike and 3' untranslated regions are different among the strains from mainland China, Hong Kong, the USA, and South Korea. Our study highlights the fact that continual surveillance is needed to trace the evolution of this virus. PMID:26475155

  7. (PCG) Protein Crystal Growth Porcine Elastase

    NASA Technical Reports Server (NTRS)

    1989-01-01

    (PCG) Protein Crystal Growth Porcine Elastase. This enzyme is associated with the degradation of lung tissue in people suffering from emphysema. It is useful in studying causes of this disease. Principal Investigator on STS-26 was Charles Bugg.

  8. Sirtuin Inhibition Adversely Affects Porcine Oocyte Meiosis

    PubMed Central

    Zhang, Liang; Ma, Rujun; Hu, Jin; Ding, Xiaolin; Xu, Yinxue

    2015-01-01

    Sirtuins have been implicated in diverse biological processes, including oxidative stress, energy metabolism, cell migration, and aging. Here, we employed Sirtuin inhibitors, nicotinamide (NAM) and Sirtinol, to investigate their effects on porcine oocyte maturation respectively. The rate of polar body extrusion in porcine oocytes decreased after treatment with NAM and Sirtinol, accompanied with the failure of cumulus cell expansion. We further found that NAM and Sirtinol significantly disrupted oocyte polarity, and inhibited the formation of actin cap and cortical granule-free domain (CGFD). Moreover, the abnormal spindles and misaligned chromosomes were readily detected during porcine oocyte maturation after treatment with NAM and Sirtinol. Together, these results suggest that Sirtuins are involved in cortical polarity and spindle organization in porcine oocytes. PMID:26176547

  9. Porcine Head Response to Blast

    PubMed Central

    Shridharani, Jay K.; Wood, Garrett W.; Panzer, Matthew B.; Capehart, Bruce P.; Nyein, Michelle K.; Radovitzky, Raul A.; Bass, Cameron R. ‘Dale’

    2012-01-01

    Recent studies have shown an increase in the frequency of traumatic brain injuries related to blast exposure. However, the mechanisms that cause blast neurotrauma are unknown. Blast neurotrauma research using computational models has been one method to elucidate that response of the brain in blast, and to identify possible mechanical correlates of injury. However, model validation against experimental data is required to ensure that the model output is representative of in vivo biomechanical response. This study exposes porcine subjects to primary blast overpressures generated using a compressed-gas shock tube. Shock tube blasts were directed to the unprotected head of each animal while the lungs and thorax were protected using ballistic protective vests similar to those employed in theater. The test conditions ranged from 110 to 740 kPa peak incident overpressure with scaled durations from 1.3 to 6.9 ms and correspond approximately with a 50% injury risk for brain bleeding and apnea in a ferret model scaled to porcine exposure. Instrumentation was placed on the porcine head to measure bulk acceleration, pressure at the surface of the head, and pressure inside the cranial cavity. Immediately after the blast, 5 of the 20 animals tested were apneic. Three subjects recovered without intervention within 30 s and the remaining two recovered within 8 min following respiratory assistance and administration of the respiratory stimulant doxapram. Gross examination of the brain revealed no indication of bleeding. Intracranial pressures ranged from 80 to 390 kPa as a result of the blast and were notably lower than the shock tube reflected pressures of 300–2830 kPa, indicating pressure attenuation by the skull up to a factor of 8.4. Peak head accelerations were measured from 385 to 3845 G’s and were well correlated with peak incident overpressure (R2 = 0.90). One SD corridors for the surface pressure, intracranial pressure (ICP), and head acceleration are

  10. Cloning and characterization of porcine resistin gene.

    PubMed

    Dai, M H; Xia, T; Chen, X D; Gan, L; Feng, S Q; Qiu, H; Peng, Y; Yang, Z Q

    2006-02-01

    Resistin is a member of resistin-like molecules (RELMs) and a hormone secreted from mature adipocytes in rodents and leukocytes in human. We now report the cloning and characterization of the full-length porcine resistin cDNA and gene. Sequence analysis indicated that the pig resistin cDNA sequence had an open reading frame of 330 bp encoding a 12 kDa protein of 109 amino acids. The deduced amino acid sequence showed 75.2% identity to the human resistin. The porcine resistin gene was composed of four exons and had exactly the same exon structure as the human resistin gene. The tissue distribution of porcine resistin mRNA was assessed by semi-quantitative RT-PCR. Resistin gene expression was the highest in porcine leukocytes and low in adipose tissue. Resistin protein could be detected in porcine serum by western blotting and it circulated in serum as dimers and trimers. We provided the first evidence that resistin was abundantly expressed in porcine leukocytes and had an expression pattern similar to that in human resistin mRNA and protein. This suggests that the pig may be a suitable animal model for studying the function of resistin in human insulin resistance. PMID:16023825

  11. Pharmacologic reduction in tumor necrosis factor activity of pulmonary alveolar macrophages.

    PubMed

    Leeper-Woodford, S K; Fisher, B J; Sugerman, H J; Fowler, A A

    1993-02-01

    Tumor necrosis factor-alpha (TNF), an inflammatory cytokine released by macrophages, may be a mediator of lung injury during septicemia. We previously reported that the cyclooxygenase inhibitor ibuprofen and histamine receptor antagonists cimetidine (H2 antagonist) and diphenhydramine (H1 antagonist) attenuate lung injury and reduce circulating TNF surges during porcine sepsis. Since pulmonary alveolar macrophages (PAM) may participate in early sepsis by producing TNF, we hypothesized that the TNF activity of PAM is reduced by ibuprofen, cimetidine, and diphenhydramine. To test this, we examined changes in PAM-derived TNF bioactivity and cell viability of freshly isolated porcine PAM during exposure to bacterial endotoxin (LPS), ibuprofen, cimetidine, and diphenhydramine. The TNF activity (% L929 cytotoxicity of PAM conditioned medium) was elevated in LPS-stimulated PAM cultures (15 to 25% increase at 1 to 6 h and 40 to 43% increase at 6 to 48 h, compared with non-LPS-stimulated cultures), and ibuprofen (150 micrograms/ml) added with LPS decreased the TNF activity for 24 h (20 to 28% reduction at 1 to 24 h). Ibuprofen added 1 h after LPS was less effective in reducing the PAM-derived TNF activity (20 to 22% reduction at 2 to 6 h). Cimetidine (112 micrograms/ml) reduced the TNF activity of LPS-stimulated PAM cultures during the first 4 h of LPS exposure (15 to 24% decrease at 1 to 4 h). Diphenhydramine (150 micrograms/ml) attenuated the PAM-derived TNF activity but also decreased viability of PAM, indicating a toxic effect of this agent on PAM.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8093999

  12. Pathogenesis of porcine Actinobacillus pleuropneumonia: Part I. Effects of surface components of Actinobacillus pleuropneumoniae in vitro and in vivo.

    PubMed Central

    Huang, H; Potter, A A; Campos, M; Leighton, F A; Willson, P J; Yates, W D

    1998-01-01

    To understand the role of non-secreted components of Actinobacillus pleuropneumoniae in virulence, we investigated in vitro cytotoxicity and in vivo pulmonary changes in pigs due to various A. pleuropneumoniae (serotype 1) fractions. Following 1.5 h incubation, lipopolysaccharide (LPS), 2 crude extracts and bacterial culture supernatant (BCS) at high concentrations were cytotoxic to porcine pulmonary alveolar macrophages (PAM), peripheral blood mononuclear leucocytes, neutrophils and a cultured porcine bone marrow cell line. Heat-killed bacteria were cytotoxic to PAM after 24 h incubation. The 2 crude extracts were prepared by shaking either intact bacteria after removing culture supernatants (crude surface extract, CSE), or whole bacterial culture (crude surface plus culture supernatant extract, CSSE) with glass beads in saline at 60 degrees C. Further experiments showed that proteins from the bacterial membrane were partially involved in cytotoxicities of these 2 extracts. Both BCS and CSSE caused multivocal hemorrhage and neutrophil infiltration when inoculated into porcine lungs, but CSE did not. The lung:whole body weight ratios of the pigs treated with CSSE were significantly higher (P < 0.05) than those of pigs treated with BCS, CSE, or control solution. It is concluded that beside the secreted proteins, bacterial surface components including LPS and non-secreted proteins were cytotoxic in vitro; and secreted and non-secreted components act synergistically to cause lung lesions. PMID:9553707

  13. An estimation of mechanical stress on alveolar walls during repetitive alveolar reopening and closure.

    PubMed

    Chen, Zheng-Long; Song, Yuan-Lin; Hu, Zhao-Yan; Zhang, Su; Chen, Ya-Zhu

    2015-08-01

    Alveolar overdistension and mechanical stresses generated by repetitive opening and closing of small airways and alveoli have been widely recognized as two primary mechanistic factors that may contribute to the development of ventilator-induced lung injury. A long-duration exposure of alveolar epithelial cells to even small, shear stresses could lead to the changes in cytoskeleton and the production of inflammatory mediators. In this paper, we have made an attempt to estimate in situ the magnitudes of mechanical stresses exerted on the alveolar walls during repetitive alveolar reopening by using a tape-peeling model of McEwan and Taylor (35). To this end, we first speculate the possible ranges of capillary number (Ca) ≡ μU/γ (a dimensionless combination of surface tension γ, fluid viscosity μ, and alveolar opening velocity U) during in vivo alveolar opening. Subsequent calculations show that increasing respiratory rate or inflation rate serves to increase the values of mechanical stresses. For a normal lung, the predicted maximum shear stresses are <15 dyn/cm(2) at all respiratory rates, whereas for a lung with elevated surface tension or viscosity, the maximum shear stress will notably increase, even at a slow respiratory rate. Similarly, the increased pressure gradients in the case of elevated surface or viscosity may lead to a pressure drop >300 dyn/cm(2) across a cell, possibly inducing epithelial hydraulic cracks. In addition, we have conceived of a geometrical model of alveolar opening to make a prediction of the positive end-expiratory pressure (PEEP) required to splint open a collapsed alveolus, which as shown by our results, covers a wide range of pressures, from several centimeters to dozens of centimeters of water, strongly depending on the underlying pulmonary conditions. The establishment of adequate regional ventilation-to-perfusion ratios may prevent recruited alveoli from reabsorption atelectasis and accordingly, reduce the required levels of

  14. Pulmonary alveolar proteinosis in a marble worker.

    PubMed

    Yildirim, Berna Botan; Akgedik, Recep; Akgedik, Sukran; Nazaroglu, Hasan

    2016-01-01

    Pulmonary alveolar proteinosis (PAP) is a rarely seen disease of the alveoli, characterized by accumulation of proteinous material, which stains positive with periodic acid Schiff, in the alveoli. Secondary PAP may develop as a result of occupational exposure to materials such as silica and indium. In the paper, together with a review of the relevant literature, we present an uncommon case of a 47-year old male, marble worker who was diagnosed with PAP associated with a 12-year history of exposure to marble dust. Int J Occup Med Environ Health 2016;29(5):871-876. PMID:27518894

  15. Lipopolysaccharide-induced epithelial monoamine oxidase mediates alveolar bone loss in a rat chronic wound model.

    PubMed

    Ekuni, Daisuke; Firth, James D; Nayer, Tarun; Tomofuji, Takaaki; Sanbe, Toshihiro; Irie, Koichiro; Yamamoto, Tatsuo; Oka, Takashi; Liu, Zhenzi; Vielkind, Juergen; Putnins, Edward E

    2009-10-01

    Reactive oxygen species (ROS) production is an antimicrobial response to pathogenic challenge that may, in the case of persistent infection, have deleterious effects on the tissue of origin. A rat periodontal disease model was used to study ROS-induced chronic epithelial inflammation and bone loss. Lipopolysaccharide (LPS) was applied for 8 weeks into the gingival sulcus, and histological analysis confirmed the onset of chronic disease. Junctional epithelium was collected from healthy and diseased animals using laser-capture microdissection, and expression microarray analysis was performed. Of 19,730 genes changed in disease, 42 were up-regulated >/=4-fold. Three of the top 10 LPS-induced genes, monoamine oxidase B (MAO/B) and flavin-containing monooxygenase 1 and 2, are implicated in ROS signaling. LPS-associated induction of the ROS mediator H(2)O(2), as well as MAO/B and tumor necrosis factor (TNF)-alpha levels were validated in the rat histological sections and a porcine junctional epithelial cell culture model. Topical MAO inhibitors significantly counteracted LPS-associated elevation of H(2)O(2) production and TNF-alpha expression in vivo and in vitro, inhibited disease-associated apical migration and proliferation of junctional epithelium and inhibited induced systemic H(2)O(2) levels and alveolar bone loss in vivo. These results suggest that LPS induces chronic wounds via elevated MAO/B-mediated increases in H(2)O(2) and TNF-alpha activity by epithelial cells and is further associated with more distant effects on systemic oxidative stress and alveolar bone loss. PMID:19779138

  16. Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

    PubMed Central

    Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

    2013-01-01

    Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival soft tissue and alveolar bone following tooth extraction. For target identification and validation, hard and soft tissue were extracted from mini-pigs at the indicated times after tooth extraction. From triplicate experiments, 56 proteins in soft tissue and 27 proteins in alveolar bone were found to be differentially expressed before and after tooth extraction. The expression of 21 of those proteins was altered in both soft tissue and bone. Comparison of the activated networks in soft tissue and alveolar bone highlighted their distinct responsibilities in bone and tissue healing. Moreover, we found that there is crosstalk between identified proteins in soft tissue and alveolar bone with respect to cellular assembly, organization, and communication. Among these proteins, we examined in detail the expression patterns and associated networks of ATP5B and fibronectin 1. ATP5B is involved in nucleic acid metabolism, small molecule biochemistry, and neurological disease, and fibronectin 1 is involved in cellular assembly, organization, and maintenance. Collectively, our findings indicate that bone regeneration is accompanied by a profound interaction among networks regulating cellular resources, and they provide novel insight into the molecular mechanisms involved in the healing of periodontal tissue after tooth extraction. PMID:23824910

  17. Silver nanowire interactions with primary human alveolar type-II epithelial cell secretions: contrasting bioreactivity with human alveolar type-I and type-II epithelial cells

    NASA Astrophysics Data System (ADS)

    Sweeney, Sinbad; Theodorou, Ioannis G.; Zambianchi, Marta; Chen, Shu; Gow, Andrew; Schwander, Stephan; Zhang, Junfeng (Jim); Chung, Kian Fan; Shaffer, Milo S. P.; Ryan, Mary P.; Porter, Alexandra E.; Tetley, Teresa D.

    2015-06-01

    Inhaled nanoparticles have a high deposition rate in the alveolar units of the deep lung. The alveolar epithelium is composed of type-I and type-II epithelial cells (ATI and ATII respectively) and is bathed in pulmonary surfactant. The effect of native human ATII cell secretions on nanoparticle toxicity is not known. We investigated the cellular uptake and toxicity of silver nanowires (AgNWs; 70 nm diameter, 1.5 μm length) with human ATI-like cells (TT1), in the absence or presence of Curosurf® (a natural porcine pulmonary surfactant with a low amount of protein) or harvested primary human ATII cell secretions (HAS; containing both the complete lipid as well as the full protein complement of human pulmonary surfactant i.e. SP-A, SP-B, SP-C and SP-D). We hypothesised that Curosurf® or HAS would confer improved protection for TT1 cells, limiting the toxicity of AgNWs. In agreement with our hypothesis, HAS reduced the inflammatory and reactive oxygen species (ROS)-generating potential of AgNWs with exposed TT1 cells. For example, IL-8 release and ROS generation was reduced by 38% and 29%, respectively, resulting in similar levels to that of the non-treated controls. However in contrast to our hypothesis, Curosurf® had no effect. We found a significant reduction in AgNW uptake by TT1 cells in the presence of HAS but not Curosurf. Furthermore, we show that the SP-A and SP-D are likely to be involved in this process as they were found to be specifically bound to the AgNWs. While ATI cells appear to be protected by HAS, evidence suggested that ATII cells, despite no uptake, were vulnerable to AgNW exposure (indicated by increased IL-8 release and ROS generation and decreased intracellular SP-A levels one day post-exposure). This study provides unique findings that may be important for the study of lung epithelial-endothelial translocation of nanoparticles in general and associated toxicity within the alveolar unit.Inhaled nanoparticles have a high deposition rate in

  18. Characteristics and EGFP expression of porcine mammary gland epithelial cells.

    PubMed

    Zheng, Yue-Mao; He, Xiao-Ying

    2010-12-01

    The aims of this study were to establish a porcine mammary gland epithelial (PMGE) cell line, and to determine if these PMGE cells could be maintained long-term in culture by continuous subculturing following transfection with a reporter gene, enhanced green fluorescence protein (EGFP). Primary culture of PMGE cells was achieved by outgrowth of migrating cells from the fragments of the mammary gland tissue of a lactating pig. The passage sixteen PMGE cells were transfected with EGFP gene using lipofection. The expression of Cell keratins of epithelial cells in PMGE cells was tested by immunofluorescence. Βeta-Casein gene mRNA was tested for PMGE cells by RT-PCR. The results showed that PMGE cells could form dome-like structure which looked like nipple, and the cells contained different cell types. The expression of Cell keratins demonstrated the property of epithelial cells, and the PMGE cells could express transcript encoding a Βeta-Casein protein. EGFP gene was successfully transferred into the PMGE cells, and the transfected cells could be maintained long-term in culture by continuous subculturing. In conclusion, we have established a EGFP gene transfected porcine mammary gland epithelial (ET-PMGE) cell line. PMID:20400167

  19. Immunological responses of swine to porcine reproductive and respiratory syndrome virus infection.

    PubMed

    Murtaugh, Michael P; Xiao, Zhengguo; Zuckermann, Federico

    2002-01-01

    The immunology of porcine reproductive and respiratory syndrome virus (PRRS) begins with an initial encounter of PRRSV with the pig. Regardless of the route of entry of PRRSV--via inhalation, intramuscular vaccination, insemination, or other routes--productive infection occurs predominately in alveolar macrophages of the lung. Thus, innate responses of the lung and the alveolar macrophage comprise the initial defense against PRRSV. The virus appears not to elicit innate interferon and cytokine responses characteristic of other strongly immunogenic viral pathogens, and its effects are consistent with induction of a weak adaptive immune response. Humoral and cell-mediated immunity is induced in due course, and results in clearance of virus from the circulation but not from lymphoid tissues, where the infection becomes persistent. Subsequent reexposure to PRRSV elicits an anamnestic response that is partially to completely protective. Within this unconventional picture of anti-PRRSV immunity lie a variety of unresolved issues, including the nature of protective immunity within individual pigs and among pigs in commercial populations, the efficacy of protective immunity against genetically different PRRSV isolates, the effects of developmental age, sex, genetics, and other host factors on the immune response to PRRSV, and the possible suppression of host immunity to other pathogens. PMID:12513925

  20. Percutaneous Irreversible Electroporation Lung Ablation: Preliminary Results in a Porcine Model

    SciTech Connect

    Deodhar, Ajita; Monette, Sebastien; Single, Gordon W.; Hamilton, William C.; Thornton, Raymond H.; Sofocleous, Constantinos T.; Maybody, Majid; Solomon, Stephen B.

    2011-12-15

    Objective: Irreversible electroporation (IRE) uses direct electrical pulses to create permanent 'pores' in cell membranes to cause cell death. In contrast to conventional modalities, IRE has a nonthermal mechanism of action. Our objective was to study the histopathological and imaging features of IRE in normal swine lung. Materials and Methods: Eleven female swine were studied for hyperacute (8 h), acute (24 h), subacute (96 h), and chronic (3 week) effects of IRE ablation in lung. Paired unipolar IRE applicators were placed under computed tomography (CT) guidance. Some applicators were deliberately positioned near bronchovascular structures. IRE pulse delivery was synchronized with the cardiac rhythm only when ablation was performed within 2 cm of the heart. Contrast-enhanced CT scan was performed immediately before and after IRE and at 1 and 3 weeks after IRE ablation. Representative tissue was stained with hematoxylin and eosin for histopathology. Results: Twenty-five ablations were created: ten hyperacute, four acute, and three subacute ablations showed alveolar edema and necrosis with necrosis of bronchial, bronchiolar, and vascular epithelium. Bronchovascular architecture was maintained. Chronic ablations showed bronchiolitis obliterans and alveolar interstitial fibrosis. Immediate post-procedure CT images showed linear or patchy density along the applicator tract. At 1 week, there was consolidation that resolved partially or completely by 3 weeks. Pneumothorax requiring chest tube developed in two animals; no significant cardiac arrhythmias were noted. Conclusion: Our preliminary porcine study demonstrates the nonthermal and extracellular matrix sparing mechanism of action of IRE. IRE is a potential alternative to thermal ablative modalities.

  1. Alveolar Epithelial Dynamics in Post-pneumonectomy Lung Growth

    PubMed Central

    Chamoto, Kenji; Gibney, Barry C.; Ackermann, Maximilian; Lee, Grace S.; Konerding, Moritz A.; Tsuda, Akira; Mentzer, Steven J.

    2013-01-01

    The intimate anatomic and functional relationship between epithelial cells and endothelial cells within the alveolus suggests the likelihood of a coordinated response during post-pneumonectomy lung growth. To define the population dynamics and potential contribution of alveolar epithelial cells to alveolar angiogenesis, we studied alveolar Type II and Type I cells during the 21 days after pneumonectomy. Alveolar Type II cells were defined and isolated by flow cytometry using a CD45−, MHC class II+, phosphine+ phenotype. These phenotypically defined alveolar Type II cells demonstrated an increase in cell number after pneumonectomy; the increase in cell number preceded the increase in Type I (T1α+) cells. Using a parabiotic wild type/GFP pneumonectomy model, less than 3% of the Type II cells and 1% of the Type I cells were positive for GFP—a finding consistent with the absence of a blood-borne contribution to alveolar epithelial cells. The CD45−, MHC class II+, phosphine+ Type II cells demonstrated the active transcription of angiogenesis-related genes both before and after pneumonectomy. When the Type II cells on day 7 after pneumonectomy were compared to non-surgical controls, 10 genes demonstrated significantly increased expression (p<.05). In contrast to the normal adult Type II cells, there was notable expression of inflammation-associated genes (Ccl2, Cxcl2, Ifng) as well as genes associated with epithelial growth (Ereg, Lep). Together, the data suggest an active contribution of local alveolar Type II cells to alveolar growth. PMID:23408540

  2. Unexplained alveolar hemorrhage associated with Ginkgo and ginseng use.

    PubMed

    Carlile, Paul V

    2015-04-01

    The author presents a case of diffuse alveolar hemorrhage in a woman consuming Ginkgo biloba extract and ginseng. The patient had no illnesses or exposures that would predispose to diffuse alveolar hemorrhage, and an extensive evaluation revealed no etiology. The patient has had no further bleeding since discontinuing Ginkgo biloba extract and ginseng 1 year ago. PMID:25887018

  3. Tongue-Palate Contact of Perceptually Acceptable Alveolar Stops

    ERIC Educational Resources Information Center

    Lee, Alice; Gibbon, Fiona E.; O'Donovan, Cliona

    2013-01-01

    Increased tongue-palate contact for perceptually acceptable alveolar stops has been observed in children with speech sound disorders (SSD). This is a retrospective study that further investigated this issue by using quantitative measures to compare the target alveolar stops /t/, /d/ and /n/ produced in words by nine children with SSD (20 tokens of…

  4. Correction of alveolar cleft with calcium-based bone substitutes.

    PubMed

    Lazarou, Spiros A; Contodimos, George B; Gkegkes, Ioannis D

    2011-05-01

    The criterion standard of alveolar cleft repair is iliac crest bone graft before secondary canine eruption. Tooth eruption has never been shown to occur in synthetic bone substitute, and there is no ideal autologous bone graft for primary repair. This prospective study evaluated alveolar cleft grafting with a calcium substitute before primary canine eruption. Ten consecutive patients with complete cleft lip, palate, and unilateral alveolar cleft with reasonably aligned arches were grafted beginning in January 2003 to March 2007. Mean age at surgery was 10.4 months. Follow-up ranged from 3 to 7 years. Radiologic evaluation of alveolar ridge was performed at the age of 4.All 10 patients were operated on by the same surgeon using the same technique, that is, conservative elevation of nasal, oral, and anterior alveolar mucosal flaps around the cleft, closure of nasal and oral flaps, placement of 1 to 3 mL of calcium substitute paste or crystals in the pocket, and closure of the anterior alveolar mucosa. All 10 patients healed without complication. Clinical evaluation revealed a well-healed arch with primary canine growth in the area of the previous cleft. Adequate normal bone formation and often a descending secondary canine were radiologically confirmed. Calcium substitutes offer significant advantages over other biomaterials as well as autologous bone grafts particularly in the primary alveolar cleft reconstruction. Our study has shown for the first time that teeth can erupt through this material, which turns into a normal functioning bone in the alveolar ridge. PMID:21558929

  5. Diffuse alveolar haemorrhage associated with aerosol propellant use

    PubMed Central

    Kelchen, Phillip; Jamous, Fady; Huntington, Mark K

    2013-01-01

    Diffuse alveolar haemorrhage (DAH) is a clinical syndrome resulting from injury to the alveolar microcirculation, most commonly associated with not only autoimmune disorders or connective tissue disease, but also a variety of infections, neoplasms and toxins. We report here a case of an otherwise healthy young man with DAH attributable to an inhalation injury resulting from use of aerosol spray paint. PMID:23955981

  6. Analysis of the Binding Sites of Porcine Sialoadhesin Receptor with PRRSV

    PubMed Central

    Jiang, Yibo; Khan, Faheem Ahmed; Pandupuspitasari, Nuruliarizki Shinta; Kadariya, Ishwari; Cheng, Zhangrui; Ren, Yuwei; Chen, Xing; Zhou, Ao; Yang, Liguo; Kong, Dexin; Zhang, Shujun

    2013-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) can infect pigs and cause enormous economic losses to the pig industry worldwide. Porcine sialoadhesin (pSN) and CD163 have been identified as key viral receptors on porcine alveolar macrophages (PAM), a main target cell infected by PRRSV. In this study, the protein structures of amino acids 1–119 from the pSN and cSN (cattle sialoadhesin) N-termini (excluding the 19-amino acid signal peptide) were modeled via homology modeling based on mSN (mouse sialoadhesin) template structures using bioinformatics tools. Subsequently, pSN and cSN homology structures were superposed onto the mSN protein structure to predict the binding sites of pSN. As a validation experiment, the SN N-terminus (including the wild-type and site-directed-mutant-types of pSN and cSN) was cloned and expressed as a SN-GFP chimera protein. The binding activity between SN and PRRSV was confirmed by WB (Western blotting), FAR-WB (far Western blotting), ELISA (enzyme-linked immunosorbent assay) and immunofluorescence assay. We found that the S107 amino acid residue in the pSN N-terminal played a crucial role in forming a special cavity, as well as a hydrogen bond for enhancing PRRSV binding during PRRSV infection. S107 may be glycosylated during PRRSV infection and may also be involved in forming the cavity for binding PRRSV along with other sites, including W2, Y44, S45, R97, R105, W106 and V109. Additionally, S107 might also be important for pSN binding with PRRSV. However, the function of these binding sites must be confirmed by further studies. PMID:24351868

  7. Actinobacillus pleuropneumoniae Possesses an Antiviral Activity against Porcine Reproductive and Respiratory Syndrome Virus

    PubMed Central

    Labrie, Josée; Hernandez Reyes, Yenney; Burciaga Nava, Jorge A.; Gagnon, Carl A.; Jacques, Mario

    2014-01-01

    Pigs are often colonized by more than one bacterial and/or viral species during respiratory tract infections. This phenomenon is known as the porcine respiratory disease complex (PRDC). Actinobacillus pleuropneumoniae (App) and porcine reproductive and respiratory syndrome virus (PRRSV) are pathogens that are frequently involved in PRDC. The main objective of this project was to study the in vitro interactions between these two pathogens and the host cells in the context of mixed infections. To fulfill this objective, PRRSV permissive cell lines such as MARC-145, SJPL, and porcine alveolar macrophages (PAM) were used. A pre-infection with PRRSV was performed at 0.5 multiplicity of infection (MOI) followed by an infection with App at 10 MOI. Bacterial adherence and cell death were compared. Results showed that PRRSV pre-infection did not affect bacterial adherence to the cells. PRRSV and App co-infection produced an additive cytotoxicity effect. Interestingly, a pre-infection of SJPL and PAM cells with App blocked completely PRRSV infection. Incubation of SJPL and PAM cells with an App cell-free culture supernatant is also sufficient to significantly block PRRSV infection. This antiviral activity is not due to LPS but rather by small molecular weight, heat-resistant App metabolites (<1 kDa). The antiviral activity was also observed in SJPL cells infected with swine influenza virus but to a much lower extent compared to PRRSV. More importantly, the PRRSV antiviral activity of App was also seen with PAM, the cells targeted by the virus in vivo during infection in pigs. The antiviral activity might be due, at least in part, to the production of interferon γ. The use of in vitro experimental models to study viral and bacterial co-infections will lead to a better understanding of the interactions between pathogens and their host cells, and could allow the development of novel prophylactic and therapeutic tools. PMID:24878741

  8. Analysis of the binding sites of porcine sialoadhesin receptor with PRRSV.

    PubMed

    Jiang, Yibo; Khan, Faheem Ahmed; Pandupuspitasari, Nuruliarizki Shinta; Kadariya, Ishwari; Cheng, Zhangrui; Ren, Yuwei; Chen, Xing; Zhou, Ao; Yang, Liguo; Kong, Dexin; Zhang, Shujun

    2013-01-01

    Porcine reproductive and respiratory syndrome virus (PRRSV) can infect pigs and cause enormous economic losses to the pig industry worldwide. Porcine sialoadhesin (pSN) and CD163 have been identified as key viral receptors on porcine alveolar macrophages (PAM), a main target cell infected by PRRSV. In this study, the protein structures of amino acids 1-119 from the pSN and cSN (cattle sialoadhesin) N-termini (excluding the 19-amino acid signal peptide) were modeled via homology modeling based on mSN (mouse sialoadhesin) template structures using bioinformatics tools. Subsequently, pSN and cSN homology structures were superposed onto the mSN protein structure to predict the binding sites of pSN. As a validation experiment, the SN N-terminus (including the wild-type and site-directed-mutant-types of pSN and cSN) was cloned and expressed as a SN-GFP chimera protein. The binding activity between SN and PRRSV was confirmed by WB (Western blotting), FAR-WB (far Western blotting), ELISA (enzyme-linked immunosorbent assay) and immunofluorescence assay. We found that the S107 amino acid residue in the pSN N-terminal played a crucial role in forming a special cavity, as well as a hydrogen bond for enhancing PRRSV binding during PRRSV infection. S107 may be glycosylated during PRRSV infection and may also be involved in forming the cavity for binding PRRSV along with other sites, including W2, Y44, S45, R97, R105, W106 and V109. Additionally, S107 might also be important for pSN binding with PRRSV. However, the function of these binding sites must be confirmed by further studies. PMID:24351868

  9. Diffuse Alveolar Hemorrhage in Acute Myeloid Leukemia.

    PubMed

    Nanjappa, Sowmya; Jeong, Daniel K; Muddaraju, Manjunath; Jeong, Katherine; Hill, Ebone D; Greene, John N

    2016-07-01

    Diffuse alveolar hemorrhage is a potentially fatal pulmonary disease syndrome that affects individuals with hematological and nonhematological malignancies. The range of inciting factors is wide for this syndrome and includes thrombocytopenia, underlying infection, coagulopathy, and the frequent use of anticoagulants, given the high incidence of venous thrombosis in this population. Dyspnea, fever, and cough are commonly presenting symptoms. However, clinical manifestations can be variable. Obvious bleeding (hemoptysis) is not always present and can pose a potential diagnostic challenge. Without prompt treatment, hypoxia that rapidly progresses to respiratory failure can occur. Diagnosis is primarily based on radiological and bronchoscopic findings. This syndrome is especially common in patients with hematological malignancies, given an even greater propensity for thrombocytopenia as a result of bone marrow suppression as well as the often prolonged immunosuppression in this patient population. The syndrome also has an increased incidence in individuals with hematological malignancies who have received a bone marrow transplant. We present a case series of 5 patients with acute myeloid leukemia presenting with diffuse alveolar hemorrhage at our institution. A comparison of clinical manifestations, radiographic findings, treatment course, and outcomes are described. A review of the literature and general overview of the diagnostic evaluation, differential diagnoses, pathophysiology, and treatment of this syndrome are discussed. PMID:27556667

  10. Biology of alveolar type II cells.

    PubMed

    Mason, Robert J

    2006-01-01

    The purpose of this review is to highlight the many metabolic properties of alveolar type II cells, their production of surfactant, their role in innate immunity, and their importance in the repair process after lung injury. The review is based on the medical literature and results from our laboratory. Type II cells produce and secrete pulmonary surfactant and for that purpose they need to synthesize the lipids of surfactant. One of the regulators of lipogenesis is the transcription factor sterol regulatory element binding protein-1c (SREBP-1c). This is a key transcription factor regulating fatty acid synthesis. Type II cells also proliferate to restore the epithelium after lung injury, clear alveolar fluid by transporting sodium from the apical to the basolateral surface, and participate in the innate immune response to inhaled materials and organisms. The type II cell is, in many ways, the defender of the alveolus. However, the type II cells work in concert with the other cells in the gas exchange regions of the lung to keep the alveoli open and reduce inflammation due to irritants in the air we breathe. PMID:16423262

  11. Effects of immunopotentiating agents on alveolar macrophage properties.

    PubMed

    Charley, B

    1986-01-01

    Infectious respiratory diseases in man and in domestic animals are characterized by the presence of a large number of different microorganisms: viruses, bacterias, mycoplasmas. It is therefore necessary to stimulate non-specific defense mechanisms in the lung and especially alveolar macrophages (AM). These cells, located in the alveolar air-spaces, play a major role in the lung clearance mechanisms and exert antibacterial, antiviral and antitumoral activities. Activation of alveolar macrophages was studied in vitro with lipopolysaccharide (LPS), lymphokines or mycobacterial derivatives (MDP). Rodent alveolar macrophages were rendered cytotoxic by in vitro exposure to LPS, free MDP or liposome-encapsulated MDP derivatives. In vivo, intravenously administered liposomes containing lipophilic MDP derivatives induced cytotoxic alveolar macrophages and protected mice against the development of pulmonary metastases. PMID:3539492

  12. Relative effects of asbestos and wollastonite on alveolar macrophages

    SciTech Connect

    Pailes, W.H.; Judy, D.J.; Resnick, H.; Castranova, V.

    1984-01-01

    Rabbit alveolar macrophages were exposed in culture to chrysotile asbestos, wollastonite, or latex, and the effects on various biochemical and physiological parameters related to cellular viability and fibrogenicity were determined. Exposure of alveolar macrophages to asbestos, wollastonite, or latex for 3 d has no effect on oxygen consumption or cellular volume. However, treatment of alveolar macrophages with as little as 25 ..mu..g asbestos/ml for 1 d increases lysosomal enzyme release and decreases membrane integrity, i.e., decreases trypan blue exclusion and increases leakage of cytosolic enzymes. In contrast, exposure of alveolar macrophages to wollastonite or latex at 250 ..mu..g/ml does not induce lysosomal enzyme release or alter membrane integrity even after 3 d of exposure in culture. These data suggest that chrysotile asbestos damages rabbit alveolar macrophages, while wollastonite, a potential substitute for asbestos, is far less cyctotoxic. 35 references, 8 figures.

  13. Development of a Consistent and Reproducible Porcine Scald Burn Model.

    PubMed

    Andrews, Christine J; Kempf, Margit; Kimble, Roy; Cuttle, Leila

    2016-01-01

    There are very few porcine burn models that replicate scald injuries similar to those encountered by children. We have developed a robust porcine burn model capable of creating reproducible scald burns for a wide range of burn conditions. The study was conducted with juvenile Large White pigs, creating replicates of burn combinations; 50°C for 1, 2, 5 and 10 minutes and 60°C, 70°C, 80°C and 90°C for 5 seconds. Visual wound examination, biopsies and Laser Doppler Imaging were performed at 1, 24 hours and at 3 and 7 days post-burn. A consistent water temperature was maintained within the scald device for long durations (49.8 ± 0.1°C when set at 50°C). The macroscopic and histologic appearance was consistent between replicates of burn conditions. For 50°C water, 10 minute duration burns showed significantly deeper tissue injury than all shorter durations at 24 hours post-burn (p ≤ 0.0001), with damage seen to increase until day 3 post-burn. For 5 second duration burns, by day 7 post-burn the 80°C and 90°C scalds had damage detected significantly deeper in the tissue than the 70°C scalds (p ≤ 0.001). A reliable and safe model of porcine scald burn injury has been successfully developed. The novel apparatus with continually refreshed water improves consistency of scald creation for long exposure times. This model allows the pathophysiology of scald burn wound creation and progression to be examined. PMID:27612153

  14. Phenotypic modulation and cytokine profiles of antigen presenting cells by European subtype 1 and 3 porcine reproductive and respiratory syndrome virus strains in vitro and in vivo.

    PubMed

    Weesendorp, Eefke; Stockhofe-Zurwieden, Norbert; Popma-De Graaf, Ditta J; Fijten, Helmi; Rebel, Johanna M J

    2013-12-27

    Porcine reproductive and respiratory syndrome virus (PRRSV) causes continuous problems in the pig industry, due to high costs of outbreaks and reduced welfare of diseased pigs. The severity of infection is, partly, dependent on the virus strain. Recently isolated Eastern-European subtype 3 strains are more pathogenic than the widespread subtype 1 strains. There is, however, almost no information available about the mechanisms involved in the pathogenicity of these subtype 3 strains. The objective of the present study was to characterize the in vitro and in vivo response of two European subtype 1 strains, Belgium A and Lelystad-Ter Huurne (LV), and a virulent subtype 3 strain, Lena, in bone marrow-derived dendritic cells (BM-DC) (in vitro) and alveolar macrophages (in vitro and in vivo). It was shown that infection with the Lena strain resulted in a higher apoptosis of cells in vitro and a higher level of infectivity in vitro and in vivo than the other virus strains. Furthermore, infection with Lena resulted in a small downregulation of the immunologically relevant cell surface molecules SLA-I, SLA-II and CD80/86 in vitro, and SLA-II in vivo. In spite of these differences, in vitro cytokine responses did not differ significantly between strains, except for the absence of IL-10 production by Lena in BM-DC. The higher infectivity, apoptosis and downregulation of the cell surface molecules, may have contributed to the increased pathogenicity of Lena, and have dampened specific immune responses. This could explain the delayed and decreased adaptive immune responses observed after infections with this strain. PMID:24120935

  15. Lentiviral vector gene transfer to porcine airways.

    PubMed

    Sinn, Patrick L; Cooney, Ashley L; Oakland, Mayumi; Dylla, Douglas E; Wallen, Tanner J; Pezzulo, Alejandro A; Chang, Eugene H; McCray, Paul B

    2012-01-01

    In this study, we investigated lentiviral vector development and transduction efficiencies in well-differentiated primary cultures of pig airway epithelia (PAE) and wild-type pigs in vivo. We noted gene transfer efficiencies similar to that observed for human airway epithelia (HAE). Interestingly, feline immunodeficiency virus (FIV)-based vectors transduced immortalized pig cells as well as pig primary cells more efficiently than HIV-1-based vectors. PAE express TRIM5α, a well-characterized species-specific lentiviral restriction factor. We contrasted the restrictive properties of porcine TRIM5α against FIV- and HIV-based vectors using gain and loss of function approaches. We observed no effect on HIV-1 or FIV conferred transgene expression in response to porcine TRIM5α overexpression or knockdown. To evaluate the ability of GP64-FIV to transduce porcine airways in vivo, we delivered vector expressing mCherry to the tracheal lobe of the lung and the ethmoid sinus of 4-week-old pigs. One week later, epithelial cells expressing mCherry were readily detected. Our findings indicate that pseudotyped FIV vectors confer similar tropisms in porcine epithelia as observed in human HAE and provide further support for the selection of GP64 as an appropriate envelope pseudotype for future preclinical gene therapy studies in the porcine model of cystic fibrosis (CF).Molecular Therapy - Nucleic Acids (2012) 1, e56; doi:10.1038/mtna.2012.47; published online 27 November 2012. PMID:23187455

  16. Restriction of Porcine Endogenous Retrovirus by Porcine APOBEC3 Cytidine Deaminases ▿

    PubMed Central

    Dörrschuck, Eva; Fischer, Nicole; Bravo, Ignacio G.; Hanschmann, Kay-Martin; Kuiper, Heidi; Spötter, Andreas; Möller, Ronny; Cichutek, Klaus; Münk, Carsten; Tönjes, Ralf R.

    2011-01-01

    Xenotransplantation of porcine cells, tissues, and organs shows promise to surmount the shortage of human donor materials. Among the barriers to pig-to-human xenotransplantation are porcine endogenous retroviruses (PERV) since functional representatives of the two polytropic classes, PERV-A and PERV-B, are able to infect human embryonic kidney cells in vitro, suggesting that a xenozoonosis in vivo could occur. To assess the capacity of human and porcine cells to counteract PERV infections, we analyzed human and porcine APOBEC3 (A3) proteins. This multigene family of cytidine deaminases contributes to the cellular intrinsic immunity and act as potent inhibitors of retroviruses and retrotransposons. Our data show that the porcine A3 gene locus on chromosome 5 consists of the two single-domain genes A3Z2 and A3Z3. The evolutionary relationships of the A3Z3 genes reflect the evolutionary history of mammals. The two A3 genes encode at least four different mRNAs: A3Z2, A3Z3, A3Z2-Z3, and A3Z2-Z3 splice variant A (SVA). Porcine and human A3s have been tested toward their antiretroviral activity against PERV and murine leukemia virus (MuLV) using novel single-round reporter viruses. The porcine A3Z2, A3Z3 and A3Z2-Z3 were packaged into PERV particles and inhibited PERV replication in a dose-dependent manner. The antiretroviral effect correlated with editing by the porcine A3s with a trinucleotide preference for 5′ TGC for A3Z2 and A3Z2-Z3 and 5′ CAC for A3Z3. These results strongly imply that human and porcine A3s could inhibit PERV replication in vivo, thereby reducing the risk of infection of human cells by PERV in the context of pig-to-human xenotransplantation. PMID:21307203

  17. Alveolar Ridge Contouring with Free Connective Tissue Graft at Implant Placement: A 5-Year Consecutive Clinical Study.

    PubMed

    Hanser, Thomas; Khoury, Fouad

    2016-01-01

    This study evaluated volume stability after alveolar ridge contouring with free connective tissue grafts at implant placement in single-tooth gaps. A total of 52 single-tooth gaps with labial volume deficiencies in the maxilla (incisors, canines, and premolars) were consecutively treated with implants and concomitant free palatal connective tissue grafts in 46 patients between 2006 and 2009. Implants had to be covered with at least 2 mm peri-implant local bone after insertion. At implant placement, a free connective tissue graft from the palate was fixed inside a labial split-thickness flap to form an existing concave buccal alveolar ridge contour due to tissue volume deficiency into a convex shape. Standardized volumetric measurements of the labial alveolar contour using a template were evaluated before connective tissue grafting and at 2 weeks, 1 year, and 5 years after implantprosthetic incorporation. Tissue volume had increased significantly (P < .05) in all six reference points representing the outer alveolar soft tissue contour of the implant before connective tissue grafting to baseline (2 weeks after implant-prosthetic incorporation). Statistically, 50% of the reference points (P > .05) kept their volume from baseline to 1 year after prosthetic incorporation and from baseline to 5 years after prosthetic incorporation, respectively, whereas reference points located within the area of the implant sulcus showed a significant (P < .05) decrease in volume. Clinically, 5 years after prosthetic incorporation the originally concave buccal alveolar contour was still convex in all implants, leading to a continuous favorable anatomical shape and improved esthetic situation. Intraoral radiographs confirmed osseointegration and stable peri-implant parameters with a survival rate of 100% after a follow-up of approximately 5 years. Implant placement with concomitant free connective tissue grafting appears to be an appropriate long-term means to contour preexisting buccal

  18. Swine alveolar macrophage cell model allows optimal replication of influenza A viruses regardless of their origin.

    PubMed

    Kasloff, Samantha B; Weingartl, Hana M

    2016-03-01

    The importance of pigs in interspecies transmission of influenza A viruses has been repeatedly demonstrated over the last century. Eleven influenza A viruses from avian, human and swine hosts were evaluated for replication phenotypes at three physiologically relevant temperatures (41°C, 37°C, 33°C) in an immortalized swine pulmonary alveolar macrophage cell line (IPAM 3D4/31) to determine whether this system would allow for their efficient replication. All isolates replicated well in IPAMs at 37°C while clear distinctions were observed at 41°C and 33°C, correlating to species of origin of the PB2, reflected in distinct amino acid residue profiles rather than in one particular PB2 residue. A strong TNF-α response was induced by some mammalian but not avian IAVs, while other selected cytokines remained below detection levels. Porcine IPAMs represent a natural host cell model for influenza virus replication where the only condition requiring modification for optimal IAV replication, regardless of virus origin. PMID:26855331

  19. Bacillus anthracis Lethal Toxin Reduces Human Alveolar Epithelial Barrier Function

    PubMed Central

    Langer, Marybeth; Duggan, Elizabeth Stewart; Booth, John Leland; Patel, Vineet Indrajit; Zander, Ryan A.; Silasi-Mansat, Robert; Ramani, Vijay; Veres, Tibor Zoltan; Prenzler, Frauke; Sewald, Katherina; Williams, Daniel M.; Coggeshall, Kenneth Mark; Awasthi, Shanjana; Lupu, Florea; Burian, Dennis; Ballard, Jimmy Dale; Braun, Armin

    2012-01-01

    The lung is the site of entry for Bacillus anthracis in inhalation anthrax, the deadliest form of the disease. Bacillus anthracis produces virulence toxins required for disease. Alveolar macrophages were considered the primary target of the Bacillus anthracis virulence factor lethal toxin because lethal toxin inhibits mouse macrophages through cleavage of MEK signaling pathway components, but we have reported that human alveolar macrophages are not a target of lethal toxin. Our current results suggest that, unlike human alveolar macrophages, the cells lining the respiratory units of the lung, alveolar epithelial cells, are a target of lethal toxin in humans. Alveolar epithelial cells expressed lethal toxin receptor protein, bound the protective antigen component of lethal toxin, and were subject to lethal-toxin-induced cleavage of multiple MEKs. These findings suggest that human alveolar epithelial cells are a target of Bacillus anthracis lethal toxin. Further, no reduction in alveolar epithelial cell viability was observed, but lethal toxin caused actin rearrangement and impaired desmosome formation, consistent with impaired barrier function as well as reduced surfactant production. Therefore, by compromising epithelial barrier function, lethal toxin may play a role in the pathogenesis of inhalation anthrax by facilitating the dissemination of Bacillus anthracis from the lung in early disease and promoting edema in late stages of the illness. PMID:23027535

  20. EFFECTS OF PAMIDRONATE ON HUMAN ALVEOLAR OSTEOBLASTS IN VITRO

    PubMed Central

    Marolt, Darja; Cozin, Matthew; Vunjak-Novakovic, Gordana; Cremers, Serge; Landesberg, Regina

    2011-01-01

    Purpose Administration of bisphosphonates has recently been associated with the development of osteonecrotic lesions of the jaw (ONJ). To elucidate the potential contributions of osteogenic cells to the development and regeneration of ONJ, we have isolated primary cells from human alveolar and long/iliac bones, and examined the effects of pamidronate on cell viability, proliferation, osteogenesis and wound healing. Materials and Methods Primary human osteoblasts and bone marrow stromal cells were isolated from alveolar and iliac/long bone and marrow tissue. Cellular proliferation, alkaline phosphatase activity, apoptosis (TUNEL, Caspase-3, and DAPI assays) and wound healing in an in vitro scratch assay were assessed after exposure to pamidronate at a range of clinically relevant doses. Results Primary alveolar osteoblasts proliferated at significantly higher rates than long/iliac bone osteoblasts in vitro. Upon exposure of alveolar osteoblasts and long/iliac bone marrow stromal cells to pamidronate for more than 72h, we have observed significantly decreased cell viability, proliferation, osteogenesis and in vitro wound healing at ≥6 × 10−5 M pamidronate, with the induction of apoptosis in ~20% of cell population. Conclusions The remodeling activity of alveolar bone, indicated by higher proliferation of alveolar osteoblasts, could be negatively affected by exposure to high concentrations of pamidronate over extended periods of time. The absence of anabolic effects of pamidronate on alveolar osteoblasts, and induction of apoptosis in osteogenic cells could negatively affect bone balance at this site, and contribute to osteonecrosis of the jaw. PMID:21856057

  1. Modern therapy for severe alveolar ridge atrophy.

    PubMed

    Chen, Yu-Feng; Pan, Chin-Yun; Wang, Wen-Chen; Lan, Ting-Hsun

    2013-01-01

    This clinical report illustrates a modern method for oral rehabilitation of severe edentulous atrophic ridge. Shallow vestibule and small denture-bearing area of the maxilla provide insufficient retention, and only the symphyseal region of the mandible has obvious alveolar ridge. The surgery of deepening vestibule of the maxilla ridge was done by using tentative miniscrew combined with old denture and soft liner. The osseointegrated dental implants were installed over symphyseal region of the mandible to act as retentive devices for prostheses. In addition, functional reline with rebase material to build buccal-tongue contact over the retromolar area after denture delivery obtained high satisfaction from the patient. Many clinical conditions cannot be managed solely with implants or preprosthetic surgery alone, whereas a combination of the 2 can achieve successful outcome. PMID:24036818

  2. Epidemiology of human alveolar echinococcosis in China.

    PubMed

    Craig, Philip S

    2006-01-01

    Globally human alveolar echinococcosis (AE) is a rare zoonotic helminthic disease confined to the Northern Hemisphere as sporadic infections in rural populations, principally in some areas of North America, west-central Europe, the Near East, Siberia, Central Asia, Japan and China. In China the first human cases were reported from western regions in the 1960s, but most hospital records remain fragmented and inadequate. From the mid-1990s mass screening surveys using portable ultrasound scanners recorded higher prevalences (up to 6% by county) than in any other areas of the world with some village rates as high as 15%. Risk factors identified for AE cases included ethnicity, sex, age and occupation. The role of the dog in transmission of Echinococcus multilocularis to humans now appears to be significant and may be one of the most important risk factor, in combination with landscape/land-use features conducive to maintaining wildlife host populations. PMID:16338167

  3. Diffuse alveolar damage associated with pulmonary thromboembolism

    PubMed Central

    Kinoshita, Yoshiaki; Sakamoto, Atsuhiko; Koga, Takaomi; Hidaka, Kouko

    2013-01-01

    In contrast to other internal organs, pulmonary arterial hypoperfusion does not always show ischemic changes in the lung parenchyma. Pulmonary thromboembolism (PTE)-related lung injury is extremely rare except in the case of pulmonary infarctions, in which PTE occasionally causes necrosis of the parenchyma. We describe the case of an 86-year-old woman who presented with respiratory failure and bilateral ground-glass opacity predominantly the upper lobes. Autopsy revealed a saddle-shaped old organized thrombi in the main pulmonary artery, relatively fresh thrombi in both pulmonary arteries, and localized diffuse alveolar damage (DAD) in the bilateral upper lung fields. The hypoperfused regions resulting from the thromboembolism anatomically coincided with the pulmonary lesion where DAD was identified. Although PTE is not regarded as a causal factor of DAD, it might induce DAD as a result of hypoperfusion in limited cases. PMID:26029610

  4. Impairment of phagocytic functions of alveolar macrophages by hydrogen peroxide

    SciTech Connect

    Oosting, R.S.; van Bree, L.; van Iwaarden, J.F.; van Golde, L.M.; Verhoef, J. )

    1990-08-01

    Hydrogen peroxide (H2O2) inhibited phagocytosis and superoxide anion production by rat alveolar macrophages. The inhibition was irreversible and concentration and exposure time dependent. The potential relationship between H2O2-induced biochemical perturbations and impaired alveolar macrophage phagocytic functions was investigated. Alveolar macrophage viability and Fc receptor binding capacity were not affected by H2O2. There was probably no correlation between a H2O2-induced rise in cytosolic (Ca2+) ((Ca2+)i) and the impairment of phagocytosis by alveolar macrophages, as was suggested by the following findings. First, the H2O2-induced rise in (Ca2+)i could be inhibited by chelation of extracellular Ca2+, whereas the H2O2-induced impairment of phagocytosis could not. Second, the H2O2-induced rise in (Ca2+)i was reversible, whereas the impairment of phagocytosis was not. And finally, a rise in (Ca2+)i by incubation of alveolar macrophages with the calcium ionophore A23187 did not affect phagocytosis. Various experiments suggested that ATP depletion may play an important role in the H2O2 toxicity for alveolar macrophages. Comparable concentrations of H2O2 caused an irreversible decrease both in cellular ATP and in phagocytosis and superoxide production by alveolar macrophages. In addition, time course of ATP depletion and induction of impaired alveolar macrophage function were similar. In view of the fact that the strong oxidant H2O2 may react with a large variety of biological substances, possible other toxic lesions may not be excluded as underlying mechanism for H2O2-induced inhibition of phagocytic functions of alveolar macrophages.

  5. Secondary alveolar bone grafting in cleft of the lip and palate patients

    PubMed Central

    Walia, Abhilashaa

    2011-01-01

    Aim: The aim was to restore the function and form of both arches with a proper occlusal relationship and eruption of tooth in the cleft area. Materials and Methods: Eleven patients were selected irrespective of sex and socio-economic status and whose age was within the mixed dentition period. Iliac crest is grafted in cleft area and subsequently evaluated for graft success using study models, and periapical and occlusal radiographs. Results: At the time of evaluation teeth were erupted in the area and good alveolar bone levels were present. Premaxilla becomes immobile with a good arch form and arch continuity. There are no major complications in terms of pain, infection, paraesthesia, hematoma formation at donor site without difficulty in walking. There is no complication in terms of pain, infection, exposure of graft, rejection of graft, and wound dehiscence at the recipient site. Discussion: It is evident that secondary alveolar grafting during the mixed dentition period is more beneficial for patients at the donor site as well as the recipient site. Conclusion: Long-term follow-up is required to achieve maximum advantage of secondary alveolar grafting; the age of the patient should be within the mixed dentition period, irrespective of sex, socio-economic status. It may be unilateral or bilateral. PMID:22090755

  6. Desquamative alveolar disease (desquamative interstitial pneumonia): case report 1

    PubMed Central

    Cruz, Edgardo; Rodriguez, Jaime; Lisboa, Carmen; Ferretti, Ricardo

    1969-01-01

    Desquamative interstitial pneumonia is a disease characterized by massive alveolar cell proliferation and desquamation with sparse interstitial involvement. The reported case shows an unusually widespread radiographic reticulo-nodular image and abundant alveolar cells in the sputum. Functional studies reveal the expected diffusion defect with practically normal mechanical properties of the lung, in contrast with interstitial fibrosing lung diseases. On the basis of the pathological findings, especially the behaviour of alveolar cells, the individuality of this disease is discussed. We think that it is different from other diseases classed as varieties of a single disease or as different entities under the names of primary interstitial fibrosis or chronic fibrosing alveolitis. Images PMID:5822250

  7. Alveolar-cell carcinoma: a problem in sputum cytodiagnosis.

    PubMed Central

    Spriggs, A I; Cole, M; Dunnill, M S

    1982-01-01

    Cytology and histology are correlated in a series of 22 cases chosen to illustrate the differential diagnosis between clusters of benign bronchial or bronchiolar cells seen in sputum, and those of alveolar cell carcinoma or adenocarcinoma with alveolar spread. Alveolar-cell carcinoma is characterised by clusters of small epithelial cells in spherical or irregular formations, none showing enough polarity to distinguish a smooth or palisaded surface. The appearances are most distinctive if vacuolation is absent. The diagnosis cannot, however, be confidently made in all cases from morphological features of cells in sputum. Images PMID:6294147

  8. Crazy paving radiography finding in asymptomatic pulmonary alveolar proteinosis.

    PubMed

    Choi, Young Rak; Chang, You-Jin; Kim, Si Wook; Choe, Kang Hyeon; Lee, Ki Man; An, Jin-Young

    2015-06-01

    Pulmonary alveolar proteinosis is a rare disorder characterized by alveolar accumulation of surfactant phospholipids and protein components. The symptoms and prognosis are extremely variable. Bronchoalveolar lavage fluid and/or transbronchial lung biopsy are useful for diagnosis; surgical lung biopsy is often unnecessary but useful in the focal involvement. We report a case of pulmonary alveolar proteinosis in a 50-year-old woman, confirmed by a video-assisted thoracoscopic surgery biopsy from the initial focal involvement, with normal bronchoalveolar lavage and transbronchial lung biopsy findings. PMID:25182335

  9. CHARACTERIZATION OF PORCINE PARVOVIRUS TYPE 3 AND PORCINE CIRCOVIRUS TYPE 2 IN WILD BOARS (SUS SCROFA) IN SLOVAKIA.

    PubMed

    Sliz, Ivan; Vlasakova, Michaela; Jackova, Anna; Vilcek, Stefan

    2015-07-01

    As the number of free-living wild boars (Sus scrofa L.) continues to rise in Slovakia, the probability of pathogen transmission between susceptible species increases. We investigated the distribution and genetic characterization of porcine parvovirus type 3 (PPV3), porcine circovirus type 2 (PCV2), and their coinfection in wild boars. Among 194 animals tested, 19.1% were positive for PPV3 and 43.8% for PCV2. Similar rates of coinfection with both viruses reaching 11.0% and 11.8% were observed in juvenile and mature wild boars, respectively. Phylogenetic analysis of PPV3 sequences from VP1 and NS1 genomic regions revealed a close genetic relationship among isolates from Slovakia and those sampled worldwide. Prevalence of PCV2 in wild boars was lower than that reported in domestic pigs in Slovakia. The PCV2 variants originating from sylvatic and domestic hosts in Slovakia were grouped in the same clusters, namely PCV2b-1A/1B and PCV2a-2D. PMID:25973618

  10. Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections.

    PubMed

    Jung, Kwonil; Renukaradhya, Gourapura J; Alekseev, Konstantin P; Fang, Ying; Tang, Yuxin; Saif, Linda J

    2009-11-01

    The innate immune response is critical for host defence against respiratory coronaviruses (CoVs). This study demonstrated that an ongoing respiratory virus infection compromises innate immune responses and affects the pathogenesis of a respiratory CoV co-infection. An innate immunosuppressive respiratory virus infection was established by infecting weaned pigs with porcine reproductive and respiratory syndrome virus (PRRSV); 10 days later, the pigs were exposed to porcine respiratory coronavirus (PRCV). The PRRSV/PRCV dual-infected pigs had reduced weight gains, a higher incidence of fever and more severe pneumonia compared with either single infection. Significant suppression of innate immune responses [reduced alpha interferon (IFN-alpha) levels in the lungs and reduced blood natural killer cell cytotoxicity] by the ongoing PRRSV infection was observed in dual-infected pigs, which coincided with exacerbated pneumonia during early PRCV infection. The subsequent PRCV infection led to enhanced PRRSV replication in the lungs and a trend towards increased serum T-helper type 1 (Th1) (IFN-gamma) but decreased Th2 [interleukin (IL)-4] responses, further exacerbating PRRSV pneumonia. Following PRCV infection, more severe PRRSV-related pulmonary alveolar macrophage (PAM) apoptosis occurred, as determined by an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay, suggesting increased PRRSV replication in PAMs. Collectively, these observations suggest interactive effects between PRCV and PRRSV via early innate (IFN-alpha) and later adaptive Th1 (IFN-gamma) and Th2 (IL-4) immune responses. These findings imply that an existing immunomodulating respiratory viral co-infection may be a contributing factor to more severe pneumonia in respiratory CoV disease. This study provides new insights into host-pathogen interactions related to co-infection by CoVs and other respiratory viruses. PMID:19656969

  11. Porcine reproductive and respiratory syndrome virus field isolates differ in in vitro interferon phenotypes.

    PubMed

    Lee, Sang-Myeong; Schommer, Susan K; Kleiboeker, Steven B

    2004-12-01

    Type I interferons (IFN-alpha and -beta) play an important role in the innate host defense against viral infection by inducing antiviral responses. In addition to direct antiviral activities, type I IFN serves as an important link between the innate and adaptive immune response through multiple mechanisms. Therefore, the outcome of a viral infection can be affected by IFN induction and the IFN sensitivity of a virus. North American porcine reproductive and respiratory syndrome virus (PRRSV) field isolates were studied with regard to IFN-alpha sensitivity and induction in order to understand the role of type I IFN in PRRSV pathogenesis. PRRSV isolates were differentially sensitive to porcine recombinant IFN-alpha (rIFN-alpha) and varied in their ability to induce IFN-alpha in porcine alveolar macrophages (PAM) cultures as measured by a porcine IFN-alpha specific ELISA on cell culture supernatants. Fifty-two plaques were purified from three PRRSV isolates (numbers 3, 7, and 12) and tested for IFN sensitivity and IFN induction. Plaque-derived populations were composed of heterogeneous populations in terms of IFN-inducing capacity and sensitivity to rIFN-alpha. When macrophages infected with isolates 3, 7, or 12 were treated with polycytidylic acid (polyI:C), IFN-alpha production was enhanced. Cells infected with isolate 3 and treated with polyI:C showed the most consistent and strongest enhancement of IFN-alpha production. It was demonstrated that the relatively low concentrations of IFN-alpha produced by isolate 3 contributed to the enhanced IFN-alpha synthesis in response to polyI:C. Isolates 7 and 12 significantly suppressed the enhanced IFN-alpha production by isolate 3 in polyI:C treated cells. To determine if suppression was at the level of IFN-alpha transcription, quantitative RT-PCR was performed for IFN-alpha mRNA and compared to GAPDH and cyclophilin mRNA quantification. However, the relative number of IFN-alpha transcript copies did not correlate with IFN

  12. Behavior of submicrometer particles in periodic alveolar airflows.

    PubMed

    Balik, G; Reis, A H; Aydin, M; Miguel, A F

    2008-04-01

    Here, we report a numerical experiment in which submicrometer particle entrainment in a periodic flow that matches those existing in the alveolus in the human lung was simulated for both sedentary and light activity. A spherical cavity with a prescribed velocity profile at the inlet was used to simulate the time-dependent periodical flow of air in the alveolus. Expansion and contraction of the alveolus were simulated by setting a conceptual permeable wall as the outer surface of the model and adjusting the boundary conditions in order to match the continuity of the flow. The simulations were conducted for breathing periods of 5 and 3 s, which match sedentary and light activity conditions, respectively, and the results were extrapolated to the real lung. It was found that, most of the particles mainly followed a straightforward path and reached the opposite side of the alveolar wall in both breathing conditions. The concentration patterns obtained are consistent with the fact that the flow within the alveolus is mainly diffusive and does not greatly depend on the flow velocity. It was found that the particles which are heavier than air move out of phase with the periodic airflow that crosses the alveolus entrance, and that these particles are significantly caught within the alveolus. Particle entrapment increases with breathing rate in accordance with experimental values and indicates that increase in breathing frequency in environments with high concentration of submicrometer particles has the consequence of increasing particle entrapment by several times with respect to normal breathing rate. PMID:18075755

  13. The localization of catalase in the pulmonary alveolar macrophage.

    PubMed

    Davies, P; Drath, D B; Engel, E E; Huber, G L

    1979-02-01

    A combined biochemical and cytochemical study of catalase was performed on alveolar macrophages lavaged from the lungs of adult male rats. Biochemically, catalase activity was present in both a high-speed granule fraction and in the supernatant. The granule-associated activity exhibited latency. Two methods of cell breakage, sonication and homogenization, yielded similar levels and distributions of catalase activity. Catalase activity in whole cells was identified cytochemically by the alkaline diaminobenzidine method and was localized within membrane-lined cytoplasmic granules similar in size to microperoxisomes and associated with cisternae of smooth endoplasmic reticulum. Localization of the reaction product was inhibited by 0.04 M aminotriazole, by cyanide, and by boiling prior to incubation. The cytochemical reaction continued in the absence of exogenous peroxide, but could be prevented by addition of catalase or pyruvate to the peroxide-free medium. Enzyme activity was also localized within a portion of the membrane-bound granules present in the cell fractions used for the biochemical assays. PMID:431040

  14. Hygienic aspects of porcine gullets.

    PubMed

    Bijker, P G; Mossel, D A; van Logtestijn, J G

    1985-01-01

    In an attempt to elaborate good manufacturing practices, including the collection, processing and storage of porcine gullets, their bacterial condition immediately after collection (100 samples), as well as that of deep frozen gullets just before incorporation into meat products (40 samples), was assessed. Fresh gullets were found to be contaminated to a high degree: poured plate colony count at 30°C (PPCC) approximately 10(6) to 10(7) and Enterobacteriaceae approximately 10(3) to 10(4) cfu g(-1). Deep frozen gullets showed even higher counts: PPCC approximately 10(7) to 10(8) and Enterobacteriaceae approximately 10(4) to 10(5) cfu g(-1). Hygiene during collection was visually assessed in six abattoirs and found to be satisfactory in two, moderate in three and poor in one. The effects of processing, by cleaning or removal of the mucus membrane, on bacterial condition, pH, colour and odour were assessed before and during storage at 4°C and 20°C. Both cleaning and removal of the mucus membrane resulted in up to approximately a tenfold reduction of colony counts. After 7 days' storage at 4°C these were significantly lower than those of unprocessed gullets (P < 0·01). Processed gullets stored at 4°C were no longer fit for consumption after 4 days' storage. It being impossible to achieve a marked improvement in the bacteriological condition of gullets, the incorporation of these products into sausages should be discouraged and their use in petfoods only allowed under reasonable conditions of hygiene and chilling. PMID:22055164

  15. Denaturing gradient gel electrophoresis as a tool to determine batch similarity of probiotic cultures of porcine cecal bacteria

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A reconstituted porcine-derived continuous-flow (RPCF) culture of gastrointestinal bacteria effective against enterotoxigenic Escherichia coli in weanling pigs has been maintained for several years and used as a parent culture from which to derive additional RPCF cultures. The integrity and health ...

  16. Complete Genome Sequences of Two Genetically Distinct Variants of Porcine Epidemic Diarrhea Virus in the Eastern Region of Thailand

    PubMed Central

    Cheun-Arom, Thaniwan; Temeeyasen, Gun; Srijangwad, Anchalee; Tripipat, Thitima; Sangmalee, Suphattra; Vui, Dam Thi; Chuanasa, Taksina; Tantituvanont, Angkana

    2015-01-01

    Porcine epidemic diarrhea virus (PEDV) has continued to cause sporadic outbreaks in Thailand since 2007. Previously, PEDV in Thailand was a new variant containing an insertion and deletion in the spike gene. Herein, full-length genome sequences are reported for two variants of PEDV isolates from pigs displaying diarrhea in Thailand. PMID:26112783

  17. Primary Cerebral Alveolar Echinococcosis: Mycology to the Rescue

    PubMed Central

    Goehringer, François; Umhang, Gérald; Gauchotte, Guillaume; Hénard, Sandrine; Boué, Franck; May, Thierry; Machouart, Marie

    2014-01-01

    A case of primary cerebral alveolar echinococcosis with a favorable outcome is reported. A universal fungal PCR enabled this diagnosis, while the initial serological analysis remained noncontributive. PMID:24478516

  18. AMBIENT PARTICULATE MATTER DECREASED IN HUMAN ALVEOLAR MACHROPHAGE CYTOKINE RELEASE

    EPA Science Inventory

    Human exposure to ambient airborne particulate matter (PM) is associated with cardiopulmonary mortality and morbidity, including increased hospitalizations for lung infection. Normal lung immune responses to bacterial infection include alveolar macrophage cytokine production and...

  19. Pulmonary Alveolar Proteinosis: A Rare Cause of Respiratory Failure.

    PubMed

    Munir, Zeeshan; Khosa, Muhammad Zeeshan; Qazi, Muhammad Yaqoob

    2015-07-01

    Pulmonary Alveolar Proteinosis (PAP) is a rare syndrome in the paediatric age group and characterized by intra-alveolar accumulation of proteinaceous phospholipid-laden material called surfactant. The diagnosis is made by High Resolution Computed Tomography (HRCT) chest which shows characteristic crazy paving appearance and diagnosis confirmed by Bronchoalveolar Lavage (BAL). We report two cases. First was a 9-month old infant who presented with respiratory distress and peripheral cyanosis since birth. He was diagnosed on High Resolution Computed Tomography (HRCT) chest as a case of pulmonary alveolar proteinosis and broncho-alveolar lavage confirmed his diagnosis. Second case was a 10-year old female child who had a history of repeated chest infections for 5 years and now presented with cough and respiratory distress for 45 days. She was also diagnosed on HRCT chest but unfortunately she died before bronchoalveolar lavage. PMID:26208564

  20. Cytotoxic effect of uranium dioxide on rat alveolar macrophages

    SciTech Connect

    Tasat, D.R.; de Rey, B.M.

    1987-10-01

    Alveolar macrophages obtained by bronchial lavage were used to assess the response of these cells to cultivation in media containing increasing concentrations of particulate UO/sub 2/. The characteristic time course of uranium effects on alveolar macrophages was determined by analyzing cell viability and incorporation of uranium particles. This study reveals the ability of alveolar macrophages to phagocytize uranium particles despite the high toxicity the metal exerts on cell membranes. However, lethal effects soon become evident. Ultrastructural analysis showed uranium particles confined within membrane bound vacuoles or free in the cytoplasm. Marked ultrastructural alterations consistent with cell death were frequently observed. The elimination of the first biological barrier hinders the scavenging of particulate contaminants in alveolar spaces, thus favoring the translocation to target organs.

  1. *Ambient Particluate Matter Supresses Alveolar Macrophage Cytokine Response to Lipopolysaccharide

    EPA Science Inventory

    Reports link ambient particulate matter (PM) exposure with cardiopulmonary mortality and morbidity, including the exacerbation of inflammatory disease and increased hospitalization for lung infections. Alveolar macrophages (AM) play an important defense role against infections v...

  2. Lung epithelial cells modulate the inflammatory response of alveolar macrophages.

    PubMed

    Rubovitch, Vardit; Gershnabel, Shoham; Kalina, Moshe

    2007-12-01

    The goal of this study was to examine the effect of alveolar epithelial cells on inflammatory responses in macrophages. Lung epithelial cells (either rat RLE-6TN or human A549 cells) reduced LPS-induced NO production in alveolar macrophages (AM) in a contact-independent mechanism. The inhibitory effect of the epithelial cells was present already at the transcriptional level: LPS-induced inducible NO synthase (iNOS) expression was significantly smaller. Surfactant protein A (SP-A)-induced NO production by alveolar macrophages was also reduced in the presence of A549 cells, though, by a different kinetics. LPS-induced interleukin-6 (IL-6) production (another inflammatory pathway) by alveolar macrophages was also reduced in the presence of RLE-6TN cells. These data suggest a role for lung epithelial cells in the complicated modulation of inflammatory processes, and provide an insight into the mechanism underlying. PMID:17851743

  3. Porcine cancer models for translational oncology

    PubMed Central

    Sieren, Jessica C.; Quelle, Dawn; Meyerholz, David K.; Rogers, Christopher S.

    2014-01-01

    Large-animal cancer models are needed to advance the development of innovative and clinically applicable tumor diagnostic, therapeutic, and monitoring technologies. We developed a genetically modified porcine model of cancer based on a TP53 mutation, and established its utility for tracking tumorigenesis in vivo through non-invasive clinical imaging approaches. PMID:27308376

  4. The Porcine Immunology and Nutrition Resource Database

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Diverse genomics-based databases have been developed to facilitate research with human and rodent models. Current porcine gene databases, however, lack the nutritional and immunological orientation and robust annotation to design effective molecular tools to study relevant pig models. To address t...

  5. Splicing variants of porcine synphilin-1.

    PubMed

    Larsen, Knud; Madsen, Lone Bruhn; Farajzadeh, Leila; Bendixen, Christian

    2015-09-01

    Parkinson's disease (PD), idiopathic and familial, is characterized by degradation of dopaminergic neurons and the presence of Lewy bodies (LB) in the substantia nigra. LBs contain aggregated proteins of which α-synuclein is the major component. The protein synphilin-1 interacts and colocalizes with α-synuclein in LBs. The aim of this study was to isolate and characterize porcine synphilin-1 and isoforms hereof with the future perspective to use the pig as a model for Parkinson's disease. The porcine SNCAIP cDNA was cloned by reverse transcriptase PCR. The spatial expression of SNCAIP mRNA was investigated by RNAseq. The presented work reports the molecular cloning and characterization of the porcine (Sus scrofa) synphilin-1 cDNA (SNCAIP) and three splice variants hereof. The porcine SNCAIP cDNA codes for a protein (synphilin-1) of 919 amino acids which shows a high similarity to human (90%) and to mouse (84%) synphilin-1. Three shorter transcript variants of the synphilin-1 gene were identified, all lacking one or more exons. SNCAIP transcripts were detected in most examined organs and tissues and the highest expression was found in brain tissues and lung. Conserved splicing variants and a novel splice form of synhilin-1 were found in this study. All synphilin-1 isoforms encoded by the identified transcript variants lack functional domains important for protein degradation. PMID:26101749

  6. Pulmonary surfactant surface tension influences alveolar capillary shape and oxygenation.

    PubMed

    Ikegami, Machiko; Weaver, Timothy E; Grant, Shawn N; Whitsett, Jeffrey A

    2009-10-01

    Alveolar capillaries are located in close proximity to the alveolar epithelium and beneath the surfactant film. We hypothesized that the shape of alveolar capillaries and accompanying oxygenation are influenced by surfactant surface tension in the alveolus. To prove our hypothesis, surfactant surface tension was regulated by conditional expression of surfactant protein (SP)-B in Sftpb(-/-) mice, thereby inhibiting surface tension-lowering properties of surfactant in vivo within 24 hours after depletion of Sftpb. Minimum surface tension of isolated surfactant was increased and oxygen saturation was significantly reduced after 2 days of SP-B deficiency in association with deformation of alveolar capillaries. Intravascularly injected 3.2-mum-diameter microbeads through jugular vein were retained within narrowed pulmonary capillaries after reduction of SP-B. Ultrastructure studies demonstrated that the capillary protrusion typical of the normal alveolar-capillary unit was reduced in size, consistent with altered pulmonary blood flow. Pulmonary hypertension and intrapulmonary shunting are commonly associated with surfactant deficiency and dysfunction in neonates and adults with respiratory distress syndromes. Increased surfactant surface tension caused by reduction in SP-B induced narrowing of alveolar capillaries and oxygen desaturation, demonstrating an important role of surface tension-lowering properties of surfactant in the regulation of pulmonary vascular perfusion. PMID:19202005

  7. Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome

    NASA Astrophysics Data System (ADS)

    Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F.; An, Gary

    2013-06-01

    Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

  8. Bayesian inference of the lung alveolar spatial model for the identification of alveolar mechanics associated with acute respiratory distress syndrome.

    PubMed

    Christley, Scott; Emr, Bryanna; Ghosh, Auyon; Satalin, Josh; Gatto, Louis; Vodovotz, Yoram; Nieman, Gary F; An, Gary

    2013-06-01

    Acute respiratory distress syndrome (ARDS) is acute lung failure secondary to severe systemic inflammation, resulting in a derangement of alveolar mechanics (i.e. the dynamic change in alveolar size and shape during tidal ventilation), leading to alveolar instability that can cause further damage to the pulmonary parenchyma. Mechanical ventilation is a mainstay in the treatment of ARDS, but may induce mechano-physical stresses on unstable alveoli, which can paradoxically propagate the cellular and molecular processes exacerbating ARDS pathology. This phenomenon is called ventilator induced lung injury (VILI), and plays a significant role in morbidity and mortality associated with ARDS. In order to identify optimal ventilation strategies to limit VILI and treat ARDS, it is necessary to understand the complex interplay between biological and physical mechanisms of VILI, first at the alveolar level, and then in aggregate at the whole-lung level. Since there is no current consensus about the underlying dynamics of alveolar mechanics, as an initial step we investigate the ventilatory dynamics of an alveolar sac (AS) with the lung alveolar spatial model (LASM), a 3D spatial biomechanical representation of the AS and its interaction with airflow pressure and the surface tension effects of pulmonary surfactant. We use the LASM to identify the mechanical ramifications of alveolar dynamics associated with ARDS. Using graphical processing unit parallel algorithms, we perform Bayesian inference on the model parameters using experimental data from rat lung under control and Tween-induced ARDS conditions. Our results provide two plausible models that recapitulate two fundamental hypotheses about volume change at the alveolar level: (1) increase in alveolar size through isotropic volume change, or (2) minimal change in AS radius with primary expansion of the mouth of the AS, with the implication that the majority of change in lung volume during the respiratory cycle occurs in the

  9. [Alveolar soft part sarcoma in pediatric patients].

    PubMed

    Paillard, Catherine; Coulomb, Aurore; Helfre, Sylvie; Orbach, Daniel

    2015-09-01

    Alveolar soft part sarcoma, ASPS, is a rare malignant tumor, with preferential primary localization in limbs, usually occurring in adolescents and young adults. This sarcoma, well defined histologically and at molecular level, has an indolent course, but a high potential metastatic pulmonary and cerebral evolution, sometimes late. ASPS is characterized by an almost specific translocation t(X, 17)(p11;25) which creates a fusion protein, APSL-TFE3, acting as an aberrant transcription factor. An in-bloc resection of the primary tumor is the treatment of choice in cases of localized disease. Conventional chemotherapy is generally ineffective. The role of radiotherapy is discussed in case of micro- or macroscopical incomplete residue. It seems to reduce local recurrence, but did not influence overall survival. The 5 years survival rate in children, adolescents and young adults is close to 80% in case of localized disease but poorer in presence of metastases. Recently, systemic anti-tumoral treatments have been focused on the use of targeted therapies. Anti-angiogenic drugs and tyrosine kinase inhibitors are the most promising approaches, but require further study. Prognostic risk factors in the literature are age (>10Y), tumor size (>5cm) and presence of metastases. This article reviews the clinical manifestations, diagnosis modalities, radiographic characteristics and therapeutic strategy of this disease in the pediatric population. PMID:26235420

  10. Cardiovascular risk in pulmonary alveolar proteinosis.

    PubMed

    Manali, Effrosyni D; Papadaki, Georgia; Konstantonis, Dimitrios; Tsangaris, Iraklis; Papaioannou, Andriana I; Kolilekas, Likurgos; Schams, Andrea; Kagouridis, Konstantinos; Karakatsani, Anna; Orfanos, Stylianos; Griese, Matthias; Papiris, Spyros A

    2016-02-01

    We hypothesized that cardiovascular events and/or indices of cardiac dysfunction may be increased in pulmonary alveolar proteinosis (PAP). Systemic and pulmonary arterial hypertension, arrhythmias, pulmonary embolism, stroke and ischemic heart attack were reported. Patients underwent serum anti-GM-CSF antibodies, disease severity score (DSS), Doppler transthoracic echocardiograph, glucose, thyroid hormones, lipids, troponin and pro-Brain natriuretic peptide (BNP) examination. Thirteen patients (8 female) were studied, median age of 47. Pro-BNP inversely related to DLCO% and TLC%; troponin directly related to DSS, age, P(A-a)O2, left atrium-, left ventricle-end-diastole diameter and BMI. On multiple regression analysis DSS was the only parameter significantly and strongly related with troponin (R(2) = 0.776, p = 0.007). No cardiovascular event was reported during follow-up. In PAP cardiovascular risk indices relate to lung disease severity. Therefore, PAP patients could be at increased risk for cardiovascular events. Quantitation of its magnitude and potential links to lungs' physiologic derangement will be addressed in future studies. PMID:26558331

  11. Therapy options in pulmonary alveolar proteinosis.

    PubMed

    Luisetti, Maurizio; Kadija, Zamir; Mariani, Francesca; Rodi, Giuseppe; Campo, Ilaria; Trapnell, Bruce C

    2010-08-01

    Pulmonary alveolar proteinosis is a rare condition characterized by the accumulation of lipoproteinaceous material within the airspaces, resulting in impaired gas transfer, and clinical manifestations ranging from asymptomatic to severe respiratory failure. To the best of the authors' knowledge, there are only a few conditions whose natural history has been so dramatically changed by the influence of advances in basic science, clinical medicine, and translational research in therapeutic approaches. Whole-lung lavage is the current standard of care and it plays a critical role as a modifier factor of the natural history of proteinosis. That notwithstanding, the identification of autoantibodies neutralizing granulocyte-macrophage colony-stimulating factor in serum and lung of patients affected by the form of proteinosis previously referred to as idiopathic, has opened the way to novel therapeutic options, such as supplementation of exogenous granulocyte-macrophage colony-stimulating factor, or strategies aimed at reducing the levels of the autoantibodies. The aim of this paper is to provide an updated review of the current therapeutic approach to proteinosis. PMID:20647242

  12. Lung vasculitis and alveolar hemorrhage: pathology.

    PubMed

    Fishbein, Gregory A; Fishbein, Michael C

    2011-06-01

    Pulmonary vasculitides are a diverse group of limited and systemic disorders associated with inflammation of pulmonary vessels and parenchyma. These diseases often have distinctive clinical, serological, and histopathological features-extrapulmonary sites of involvement, circulating autoantibodies, predispositions for small or large vessels, and others. Some have characteristic inflammatory lesions; others are characterized by the absence of such lesions. Frequently pathological findings overlap, rendering classification, and diagnosis a challenge. The anti-neutrophil cytoplasmic antibody (ANCA)-associated small-vessel diseases constitute the major pulmonary vasculitides. These include Wegener granulomatosis (WG), Churg Strauss syndrome (CSS), and microscopic polyangiitis (MPA). Less frequently, diseases such as polyarteritis nodosa, Takayasu arteritis, Behçet syndrome, and connective tissue diseases may involve pulmonary vessels, but these entities are better associated with extrapulmonary disease. Diffuse alveolar hemorrhage (DAH) is a severe manifestation of pulmonary vasculitis. DAH is most commonly seen in small-vessel vasculitides, specifically MPA and WG. Other syndromes associated with DAH include Goodpasture syndrome, Henoch-Schönlein purpura, and systemic lupus erythematosus. Less commonly, DAH may be secondary to infection or drugs/toxins. Furthermore, in the absence of discernable systemic disease, DAH may be idiopathic-referred to as isolated pulmonary capillaritis (IPC) or idiopathic pulmonary hemosiderosis (IPH), depending on the presence of capillaritis. PMID:21674412

  13. Populations at Risk for Alveolar Echinococcosis, France

    PubMed Central

    Piarroux, Martine; Piarroux, Renaud; Knapp, Jenny; Bardonnet, Karine; Dumortier, Jérôme; Watelet, Jérôme; Gerard, Alain; Beytout, Jean; Abergel, Armand; Bresson-Hadni, Solange

    2013-01-01

    During 1982–2007, alveolar echinococcosis (AE) was diagnosed in 407 patients in France, a country previously known to register half of all European patients. To better define high-risk groups in France, we conducted a national registry-based study to identify areas where persons were at risk and spatial clusters of cases. We interviewed 180 AE patients about their way of life and compared responses to those of 517 controls. We found that almost all AE patients lived in 22 départements in eastern and central France (relative risk 78.63, 95% CI 52.84–117.02). Classification and regression tree analysis showed that the main risk factor was living in AE-endemic areas. There, most at-risk populations lived in rural settings (odds ratio [OR] 66.67, 95% CI 6.21–464.51 for farmers and OR 6.98, 95% CI 2.88–18.25 for other persons) or gardened in nonrural settings (OR 4.30, 95% CI 1.82–10.91). These findings can help sensitization campaigns focus on specific groups. PMID:23647623

  14. Alveolar rhabdomyosarcoma after treatment of osteosarcoma.

    PubMed

    Kasahara, Yasushi; Iwabuchi, Haruko; Takachi, Takayuki; Hosokai, Ryosuke; Yoshida, Sakiko; Imamura, Masaru; Watanabe, Akihiro; Umezu, Hajime; Hotta, Tetsuo; Ogose, Akira; Imai, Chihaya

    2013-08-01

    Secondary rhabdomyosarcoma (RMS) after treatment of osteosarcoma (OS) is rare. Reported here is the case of a metachronous RMS in the nasal cavity, developing 12 years after successful treatment of non-metastatic OS. The patient was diagnosed as having OS of the femur at 2 years of age. Chemotherapy for OS included doxorubicin (cumulative dose, 488 mg/m(2) ). No radiotherapy was given. There was no family history suggestive of cancer predisposition syndrome. At 14 years of age, alveolar RMS was diagnosed on histopathology. PAX3-FKHR fusion transcripts were detected on reverse transcription-polymerase chain reaction. Germline TP53 mutation was not seen on standard DNA sequencing. The occurrence of secondary sarcomas, in the Children's Cancer Survivor study conducted in North America, has been associated with high cumulative doses of anthracyclines, which may also have played a role in the development of RMS in the present case. In the future, novel molecular technologies might uncover genetic cancer predisposition in patients with metachronous cancers. PMID:23910806

  15. Immunoproteasome dysfunction augments alternative polarization of alveolar macrophages.

    PubMed

    Chen, S; Kammerl, I E; Vosyka, O; Baumann, T; Yu, Y; Wu, Y; Irmler, M; Overkleeft, H S; Beckers, J; Eickelberg, O; Meiners, S; Stoeger, T

    2016-06-01

    The proteasome is a central regulatory hub for intracellular signaling by degrading numerous signaling mediators. Immunoproteasomes are specialized types of proteasomes involved in shaping adaptive immune responses, but their role in innate immune signaling is still elusive. Here, we analyzed immunoproteasome function for polarization of alveolar macrophages, highly specialized tissue macrophages of the alveolar lung surface. Classical activation (M1 polarization) of primary alveolar macrophages by LPS/IFNγ transcriptionally induced all three immunoproteasome subunits, low molecular mass protein 2 (LMP2), LMP7 and multicatalytic endopeptidase complex-like 1, which was accompanied by increased immunoproteasome activity in M1 cells. Deficiency of LMP7 had no effect on the LPS/IFNγ-triggered M1 profile indicating that immunoproteasome function is dispensable for classical alveolar macrophage activation. In contrast, IL-4 triggered alternative (M2) activation of primary alveolar macrophages was accompanied by a transcriptionally independent amplified expression of LMP2 and LMP7 and an increase in immunoproteasome activity. Alveolar macrophages from LMP7 knockout mice disclosed a distorted M2 profile upon IL-4 stimulation as characterized by increased M2 marker gene expression and CCL17 cytokine release. Comparative transcriptome analysis revealed enrichment of IL-4-responsive genes and of genes involved in cellular response to defense, wounding and inflammation in LMP7-deficient alveolar macrophages indicating a distinct M2 inflammation resolving phenotype. Moreover, augmented M2 polarization was accompanied by amplified AKT/STAT6 activation and increased RNA and protein expression of the M2 master transcription factor interferon regulatory factor 4 in LMP7(-/-) alveolar macrophages. IL-13 stimulation of LMP7-deficient macrophages induced a similar M2-skewed profile indicative for augmented signaling via the IL-4 receptor α (IL4Rα). IL4Rα expression was generally

  16. Modeling Alveolar Epithelial Cell Behavior In Spatially Designed Hydrogel Microenvironments

    NASA Astrophysics Data System (ADS)

    Lewis, Katherine Jean Reeder

    The alveolar epithelium consists of two cell phenotypes, elongated alveolar type I cells (AT1) and rounded alveolar type II cells (ATII), and exists in a complex three-dimensional environment as a polarized cell layer attached to a thin basement membrane and enclosing a roughly spherical lumen. Closely surrounding the alveolar cysts are capillary endothelial cells as well as interstitial pulmonary fibroblasts. Many factors are thought to influence alveolar epithelial cell differentiation during lung development and wound repair, including physical and biochemical signals from the extracellular matrix (ECM), and paracrine signals from the surrounding mesenchyme. In particular, disrupted signaling between the alveolar epithelium and local fibroblasts has been implicated in the progression of several pulmonary diseases. However, given the complexity of alveolar tissue architecture and the multitude of signaling pathways involved, designing appropriate experimental platforms for this biological system has been difficult. In order to isolate key factors regulating cellular behavior, the researcher ideally should have control over biophysical properties of the ECM, as well as the ability to organize multiple cell types within the scaffold. This thesis aimed to develop a 3D synthetic hydrogel platform to control alveolar epithelial cyst formation, which could then be used to explore how extracellular cues influence cell behavior in a tissue-relevant cellular arrangement. To accomplish this, a poly(ethylene glycol) (PEG) hydrogel network containing enzymatically-degradable crosslinks and bioadhesive pendant peptides was employed as a base material for encapsulating primary alveolar epithelial cells. First, an array of microwells of various cross-sectional shapes was photopatterned into a PEG gel containing photo-labile crosslinks, and primary ATII cells were seeded into the wells to examine the role of geometric confinement on differentiation and multicellular arrangement

  17. Production of monoclonal antibodies to porcine interleukin-18 and their use for immunoaffinity purification of recombinant porcine interleukin-18.

    PubMed

    Muneta, Y; Shimoji, Y; Yokomizo, Y; Mori, Y

    2000-03-01

    We have recently reported the cloning and expression of porcine interleukin-18 (IL-18). In this study, we describe the production of anti-porcine IL-18 monoclonal antibodies (mAb) and their use in the purification of a large amount of recombinant porcine IL-18 by immunoaffinity column chromatography. Five monoclonal antibodies (2-2-B, 2-5-B, 2-13-C, 3-1-C and 5-3-B) were established and characterized. Three (2-2-B, 3-1-C and 5-3-B) of them were of IgG1 subclass, and the other two were IgMs. Epitope analysis of the three IgG1 mAbs showed that they recognized the same epitope. All five mAbs demonstrated reactivity with baculovirus generated porcine IL-18 by immunoblot analysis. Biologically active porcine IL-18 was obtained by immunoaffinity chromatography using anti-porcine IL-18 mAb at more than 85% purity from culture supernatants of Trichoplusia ni (Tn5) derived cells infected with recombinant baculovirus containing the coding sequence of porcine mature IL-18. These results suggest that the anti-porcine IL-18 mAbs established in this study are useful for one-step purification of porcine mature IL-18 as well as the detection of porcine IL-18 by immunoblotting. PMID:10699583

  18. Porcine Parvovirus: Natural and Experimental Infections of the Porcine Fetus and Prevalence In Mature Swine 1

    PubMed Central

    Redman, D. R.; Bohl, E. H.; Ferguson, L. C.

    1974-01-01

    Antibodies against porcine parvovirus were detected in 17 of 116 prenursing pig sera. Antibodies against transmissible gastroenteritis or ECPO-6 (an enterovirus) were not detected in prenursing sera of the pigs tested. Seventy-seven percent of 129 serum samples from 23 Ohio farms and 82% of 96 samples from slaughter plants in Ohio were serologically positive for porcine parvovirus. Mummies or other abnormalities were not observed in newly born pigs exposed to porcine parvovirus by the transuterine route 101 days after gestation. Indirect evidence suggested that the virus had not spread to other fet uses following exposure after 101 days at least not in a sufficient amount of time to stimulate detectable antibody. Direct intrafetal exposure to porcine parvovirus (i.m. injection, transutero) after 62 days of gestation resulted in dealth and mummification of the two fetuses, and apparently in the subsequent spread of the virus, as five of nine live pigs born were serologically positive for porcine parvovirus and these five pigs had not been injected with the virus. Immunoglobulin G was detected in all newborn pigs irregardless of known antigenic stimulation or the presence of specific antibody. In general, the presence of immunoglobulin M or immunoglobulin A in fetal serum was correlated with a history of antigenic stimulation or the presence of detectable antibody. PMID:4426705

  19. Coincidental detection of genomes of porcine parvoviruses and porcine circovirus type 2 infecting pigs in Japan

    PubMed Central

    SAEKHOW, Prayuth; KISHIZUKA, Shingo; SANO, Natsuha; MITSUI, Hiroko; AKASAKI, Hajime; MAWATARI, Takahiro; IKEDA, Hidetoshi

    2015-01-01

    The infection status of 15 viruses in 120 pigs aged about 6 months was investigated based on tonsil specimens collected from a slaughterhouse. Only 5 species of porcine parvoviruses and porcine circovirus type 2 (PCV2) were detected at high frequencies; 67% for porcine parvovirus (PPV) (PPV-Kr or -NADL2 as the new abbreviation), 58% for PPV2 (CnP-PARV4), 39% for PPV3 (P-PARV4), 33% for PPV4 (PPV4), 55% for PBo-likeV (PBoV7) and 80% for PCV2. A phylogenetic analysis of PPV3 suggested that Japanese PPV3s showed a slight variation, and possibly, there were farms harboring homogeneous or heterogeneous PPV3s. Statistical analyses indicated that the detection of PCV2 was significantly coincidental with each detection of PPV, PPV2 and PPV3, and PPV and PPV4 were also coincidentally detected. The concurrent infection with PCV2 and porcine parvoviruses in the subclinically infected pigs may resemble the infection status of pigs with the clinical manifestations of porcine circovirus associated disease which occurs in 3–5 months old pigs and is thought to be primarily caused by the PCV2 infection. PMID:26166811

  20. Coincidental detection of genomes of porcine parvoviruses and porcine circovirus type 2 infecting pigs in Japan.

    PubMed

    Saekhow, Prayuth; Kishizuka, Shingo; Sano, Natsuha; Mitsui, Hiroko; Akasaki, Hajime; Mawatari, Takahiro; Ikeda, Hidetoshi

    2016-01-01

    The infection status of 15 viruses in 120 pigs aged about 6 months was investigated based on tonsil specimens collected from a slaughterhouse. Only 5 species of porcine parvoviruses and porcine circovirus type 2 (PCV2) were detected at high frequencies; 67% for porcine parvovirus (PPV) (PPV-Kr or -NADL2 as the new abbreviation), 58% for PPV2 (CnP-PARV4), 39% for PPV3 (P-PARV4), 33% for PPV4 (PPV4), 55% for PBo-likeV (PBoV7) and 80% for PCV2. A phylogenetic analysis of PPV3 suggested that Japanese PPV3s showed a slight variation, and possibly, there were farms harboring homogeneous or heterogeneous PPV3s. Statistical analyses indicated that the detection of PCV2 was significantly coincidental with each detection of PPV, PPV2 and PPV3, and PPV and PPV4 were also coincidentally detected. The concurrent infection with PCV2 and porcine parvoviruses in the subclinically infected pigs may resemble the infection status of pigs with the clinical manifestations of porcine circovirus associated disease which occurs in 3-5 months old pigs and is thought to be primarily caused by the PCV2 infection. PMID:26166811

  1. Tissue Distribution of Porcine FTO and Its Effect on Porcine Intramuscular Preadipocytes Proliferation and Differentiation

    PubMed Central

    Chen, Xiaoling; Zhou, Bo; Luo, Yanliu; Huang, Zhiqing; Jia, Gang; Liu, Guangmang; Zhao, Hua

    2016-01-01

    The fat mass and obesity associated (FTO) gene plays an important role in adipogenesis. However, its function during porcine intramuscular preadipocyte proliferation and differentiation remains poorly understood. In this study, we prepared the antiserum against porcine FTO (pFTO), which was used to determine its subcellular localization and tissue distribution. Our data indicated that pFTO was localized predominantly in the nucleus. Real-time quantitative PCR and western blot analysis showed that pFTO was highly expressed in the lung and subcutaneous adipose tissue. Overexpression of pFTO in porcine intramuscular preadipocytes significantly promoted cell proliferation and lipid deposition. Furthermore, overexpression of pFTO in differentiating porcine intramuscular preadipocytes also significantly increased the mRNA levels of adipocyte differentiation transcription factors peroxisome proliferators-activated receptor γ (PPARγ), CCAAT/enhancer binding protein α (C/EBPα), lipoprotein lipase (LPL) and fatty acid synthase (FAS). Our findings provide the first functional evidence to reveal a role of pFTO in porcine intramuscular preadipocyte proliferation and differentiation. PMID:26964098

  2. Stability of Reference Gene Expression After Porcine Sapelovirus Infection in Porcine Intestinal Epithelial Cells.

    PubMed

    Huang, Yong; Chen, Yabing; Sun, Huan; Lan, Daoliang

    2016-01-01

    Intestinal epithelial cells, which serve as the first physical barrier to protect intestinal tract from external antigens, have an important role in the local innate immunity. Screening of reference genes that have stable expression levels after viral infection in porcine intestinal epithelial cells is critical for ensuring the reliability of the expression analysis on anti-infection genes in porcine intestinal epithelial cells. In this study, nine common reference genes in pigs, including ACTB, B2M, GAPDH, HMBS, SDHA, HPRT1, TBP, YWHAZ, and RPL32, were chosen as the candidate reference genes. Porcine sapelovirus (PSV) was used as a model virus to infect porcine intestinal epithelial cell line (IPEC-J2). The expression stability of the nine genes was assessed by the geNorm, NormFinder, and BestKeeper software. Moreover, RefFinder program was used to evaluate the analytical results of above three softwares, and a relative expression experiment of selected target gene was used to verify the analysis results. The comprehensive results indicated that the gene combination of TBP and RPL32 has the most stable expression, which could be considered as an appropriate reference gene for research on gene expression after PSV infection in IPEC-J2cells. The results provided essential data for expression analysis of anti-infection genes in porcine intestinal epithelial cells. PMID:27092424

  3. The Global Burden of Alveolar Echinococcosis

    PubMed Central

    Torgerson, Paul R.; Keller, Krista; Magnotta, Mellissa; Ragland, Natalie

    2010-01-01

    Background Human alveolar echinococcosis (AE) is known to be common in certain rural communities in China whilst it is generally rare and sporadic elsewhere. The objective of this study was to provide a first estimate of the global incidence of this disease by country. The second objective was to estimate the global disease burden using age and gender stratified incidences and estimated life expectancy with the disease from previous results of survival analysis. Disability weights were suggested from previous burden studies on echinococcosis. Methodology/Principal Findings We undertook a detailed review of published literature and data from other sources. We were unable to make a standardised systematic review as the quality of the data was highly variable from different countries and hence if we had used uniform inclusion criteria many endemic areas lacking data would not have been included. Therefore we used evidence based stochastic techniques to model uncertainty and other modelling and estimating techniques, particularly in regions where data quality was poor. We were able to make an estimate of the annual global incidence of disease and annual disease burden using standard techniques for calculation of DALYs. Our studies suggest that there are approximately 18,235 (CIs 11,900–28,200) new cases of AE per annum globally with 16,629 (91%) occurring in China and 1,606 outside China. Most of these cases are in regions where there is little treatment available and therefore will be fatal cases. Based on using disability weights for hepatic carcinoma and estimated age and gender specific incidence we were able to calculate that AE results in a median of 666,434 DALYs per annum (CIs 331,000-1.3 million). Conclusions/Significance The global burden of AE is comparable to several diseases in the neglected tropical disease cluster and is likely to be one of the most important diseases in certain communities in rural China on the Tibetan plateau. PMID:20582310

  4. Characterization of two novel porcine reproductive and respiratory syndrome virus isolates with deletions in the GP2 gene.

    PubMed

    Chen, Jia-zeng; Peng, Jin-mei; Bai, Yun; Wang, Qian; Liu, Yi-min; Zhang, Qiu-yue; Chang, Dan; Zhang, Wu-chao; Zhao, Hong-yuan; Ye, Chao; An, Tong-qing; Cai, Xue-hui; Tian, Zhi-jun; Tong, Guang-zhi

    2015-04-17

    Two newly emerged, porcine reproductive and respiratory syndrome virus (PRRSV) strains (Henan-A10 and A11) were isolated from the sera of aborting sows. Interestingly, both of the isolates could replicate in primary porcine alveolar macrophage (PAM) cells but not in MARC-145 cells. A phylogenetic tree based on the complete genome was constructed and the results showed that Henan-A10 and A11 were most closely related to other highly pathogenic PRRSV (HP-PRRSV) strains. However, genomic sequence analysis showed that Henan-A10 and A11 shared only 96.8-97.8% nucleotide identity with the representative HP-PRRSV strain JXA1. Notably, a 10 amino acids deletion in the GP2 endodomain was identified for the first time. A full-length, infectious cDNA clone of HuN4-F112 (attenuated strain from a HP-PRRSV) was used to construct a chimeric clone with the corresponding deletion in GP2. We found that the deletion did not affect viral growth in MARC-145 cells, indicating that the endodomain of PRRSV GP2 may be variable. PMID:25669596

  5. Cellular miR-130b inhibits replication of porcine reproductive and respiratory syndrome virus in vitro and in vivo.

    PubMed

    Li, Liwei; Gao, Fei; Jiang, Yifeng; Yu, Lingxue; Zhou, Yanjun; Zheng, Hao; Tong, Wu; Yang, Shen; Xia, Tianqi; Qu, Zehui; Tong, Guangzhi

    2015-01-01

    MicroRNAs (miRNAs) can impact viral infections by binding to sequences with partial complementarity on viral RNA transcripts, usually resulting in the repression of virus replication. In the present study, we identified a potential binding site for miR-130 in the 5' untranslated region (bps 155-162) of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. We found that the delivery of multiple miR-130 family mimics, especially miR-130b, resulted in inhibition of PRRSV replication in vitro. miR-130 was effective in inhibiting the replication of multiple type 2 PRRSV strains, but not against vSHE, a classical type 1 strain. miR-130 over-expression did not induce IFN-α or TNF-α expression in either uninfected or PRRSV-infected porcine alveolar macrophages. Results from luciferase reporter assays indicated that miR-130 directly targeted the PRRSV 5' UTR. Intranasal inoculation of piglets with miR-130b exhibited antiviral activity in vivo and partially protected piglets from an otherwise lethal challenge with HP-PRRSV strain vJX143. Overall, these results demonstrate the importance of the miR-130 family in modulating PRRSV replication and also provide a scientific basis for using cellular miRNAs in anti-PRRSV therapies. PMID:26581169

  6. Cellular miR-130b inhibits replication of porcine reproductive and respiratory syndrome virus in vitro and in vivo

    PubMed Central

    Li, Liwei; Gao, Fei; Jiang, Yifeng; Yu, Lingxue; Zhou, Yanjun; Zheng, Hao; Tong, Wu; Yang, Shen; Xia, Tianqi; Qu, Zehui; Tong, Guangzhi

    2015-01-01

    MicroRNAs (miRNAs) can impact viral infections by binding to sequences with partial complementarity on viral RNA transcripts, usually resulting in the repression of virus replication. In the present study, we identified a potential binding site for miR-130 in the 5′ untranslated region (bps 155-162) of the porcine reproductive and respiratory syndrome virus (PRRSV) genome. We found that the delivery of multiple miR-130 family mimics, especially miR-130b, resulted in inhibition of PRRSV replication in vitro. miR-130 was effective in inhibiting the replication of multiple type 2 PRRSV strains, but not against vSHE, a classical type 1 strain. miR-130 over-expression did not induce IFN-α or TNF-α expression in either uninfected or PRRSV-infected porcine alveolar macrophages. Results from luciferase reporter assays indicated that miR-130 directly targeted the PRRSV 5′ UTR. Intranasal inoculation of piglets with miR-130b exhibited antiviral activity in vivo and partially protected piglets from an otherwise lethal challenge with HP-PRRSV strain vJX143. Overall, these results demonstrate the importance of the miR-130 family in modulating PRRSV replication and also provide a scientific basis for using cellular miRNAs in anti-PRRSV therapies. PMID:26581169

  7. Persistence of porcine reproductive and respiratory syndrome virus infection in a swine operation.

    PubMed Central

    Bilodeau, R; Archambault, D; Vézina, S A; Sauvageau, R; Fournier, M; Dea, S

    1994-01-01

    A herd of Quebec seedstock pigs experienced in early 1992 a typical outbreak of porcine reproductive and respiratory syndrome (PRRS) associated with lesions of interstitial, proliferative and necrotizing pneumonia in weaned piglets. The nature of the infection was confirmed by serology using indirect immunofluorescence (IIF) and virus isolation in primary cultures of porcine alveolar macrophages (PAM). Farm production recovered after eight weeks of losses. In order to evaluate the persistence of infection in the herd, five SPF-piglets were introduced in two different sections of the PRRS-affected barn four months after the disappearance of clinical symptoms, and two others were placed in a neighboring building with apparently healthy farrow-to-finnish pigs. Clinical signs, body temperature, humoral immune response, virological and histopathological findings were recorded over a 42-day period. Clinical signs were evident in all of the sentinels and prolonged fever (> or = 40 degrees C) was recorded one day post-exposure (PE). Antibody titers to PRRS virus could be detected by IIF on PAM seven days PE, and reached 1:1024 by day 21 PE. Three of the sentinels developed significant virus neutralizing antibody titers (> 1:8 to < or = 1:128) by day 35 PE. In all cases, the virus could be isolated from the serum between day 7 and 42 PE. Thus, the virus and specific antibodies coexisted for several weeks. Lesions of interstitial pneumonia was demonstrated in few animals. In experimental inoculation studies, the viral strain isolated from the sentinel pigs produced severe reproductive disorders in two sows inoculated at 95 days of gestation.(ABSTRACT TRUNCATED AT 250 WORDS) Images Fig. 2. PMID:7889462

  8. Molecular mobility in the monolayers of foam films stabilized by porcine lung surfactant.

    PubMed Central

    Lalchev, Z I; Todorov, R K; Christova, Y T; Wilde, P J; Mackie, A R; Clark, D C

    1996-01-01

    Certain physical properties of a range of foam film types that are believed to exist in vivo in the lung have been investigated. The contribution of different lung surfactant components found in porcine lung surfactant to molecular surface diffusion in the plane of foam films has been investigated for the first time. The influence of the type and thickness of black foam films, temperature, electrolyte concentration, and extract composition on surface diffusion has been studied using the fluorescence recovery after photobleaching technique. Fluorescent phospholipid probe molecules in foam films stabilized by porcine lung surfactant samples or their hydrophobic extracts consisting of surfactant lipids and hydrophobic lung surfactant proteins, SP-B and SP-C, exhibited more rapid diffusion than observed in films of its principal lipid component alone, L-alpha-phosphatidylcholine dipalmitoyl. This effect appears to be due to contributions from minor lipid components present in the total surfactant lipid extracts. The minor lipid components influence the surface diffusion in foam films both by their negative charge and by lowering the phase transition temperature of lung surfactant samples. In contrast, the presence of high concentrations of the hydrophillic surfactant protein A (SP-A) and non-lung-surfactant proteins in the sample reduced the diffusion coefficient (D) of the lipid analog in the adsorbed layer of the films. Hysteresis behavior of D was observed during temperature cycling, with the cooling curve lying above the heating curve. However, in cases where some surface molecular aggregation and surface heterogeneity were observed during cooling, the films became more rigid and molecules at the interfaces became immobilized. The thickness, size, capillary pressure, configuration, and composition of foam films of lung surfactant prepared in vitro support their investigation as realistic structural analogs of the surface films that exist in vivo in the lung

  9. Alveolar targeting of aerosol pentamidine. Toward a rational delivery system

    SciTech Connect

    Simonds, A.K.; Newman, S.P.; Johnson, M.A.; Talaee, N.; Lee, C.A.; Clarke, S.W. )

    1990-04-01

    Nebulizer systems that deposit a high proportion of aerosolized pentamidine on large airways are likely to be associated with marked adverse side effects, which may lead to premature cessation of treatment. We have measured alveolar deposition and large airway-related side effects (e.g., cough, breathlessness, and effect on pulmonary function) after aerosolization of 150 mg pentamidine isethionate labeled with {sup 99m}Tc-Sn-colloid. Nine patients with AIDS were studied using three nebulizer systems producing different droplet size profiles: the Acorn System 22, Respirgard II, and Respirgard II with the inspiratory baffle removed. Alveolar deposition was greatest and side effects least with the nebulizer producing the smallest droplet size profile (Respirgard II), whereas large airway-related side effects were prominent and alveolar deposition lowest with the nebulizer producing the largest droplet size (Acorn System 22). Values for alveolar deposition and adverse airway effects were intermediate using the Respirgard with inspiratory baffle removed, thus indicating the importance of the baffle valve in determining droplet size. Addition of a similar baffle valve to the Acorn System 22 produced a marked improvement in droplet size profile. Selection of a nebulizer that produces an optimal droplet size range offers the advantage of enhancing alveolar targeting of aerosolized pentamidine while reducing large airway-related side effects.

  10. Retinoic acid in alveolar development, maintenance and regeneration.

    PubMed Central

    Maden, Malcolm; Hind, Matthew

    2004-01-01

    Recent data suggest that exogenous retinoic acid (RA), the biologically active derivative of vitamin A, can induce alveolar regeneration in a rat model of experimental emphysema. Here, we describe a mouse model of disrupted alveolar development using dexamethasone administered postnatally. We show that the effects of dexamethasone are concentration dependent, dose dependent, long lasting and result in a severe loss of alveolar surface area. When RA is administered to these animals as adults, lung architecture and the surface area per unit of body weight are completely restored to normal. This remarkable effect may be because RA is required during normal alveolar development and administering RA re-awakens gene cascades used during development. We provide evidence that RA is required during alveologenesis in the mouse by showing that the levels of the retinoid binding proteins, the RA receptors and two RA synthesizing enzymes peak postnatally. Furthermore, an inhibitor of RA synthesis, disulphiram, disrupts alveologenesis. We also show that RA is required throughout life for the maintenance of lung alveoli because when rats are deprived of dietary retinol they lose alveoli and show the features of emphysema. Alveolar regeneration with RA may therefore be an important novel therapeutic approach to the treatment of respiratory diseases characterized by a reduced gas-exchanging surface area such as bronchopulmonary dysplasia and emphysema for which there are currently no treatments. PMID:15293808