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Sample records for adenovirus hemorrhagic disease

  1. Hemorrhagic cerebrovascular disease.

    PubMed

    Romero, Javier M; Rosand, Jonathan

    2016-01-01

    Primary or nontraumatic spontaneous intracerebral hemorrhage (ICH) accounts for 10-15% of all strokes, and has a poor prognosis. ICH has a mortality rate of almost 50% when associated with intraventricular hemorrhage within the first month, and 80% rate of dependency at 6 months from onset. Neuroimaging is critical in identifying the underlying etiology and thus assisting in the important therapeutic decisions. There are several imaging modalities available in the workup of patients who present with ICH, including computed tomography (CT), magnetic resonance imaging (MRI), and digital subtraction angiography (DSA). A review of the current imaging approach, as well as a differential diagnosis of etiologies and imaging manifestations of primary versus secondary intraparenchymal hemorrhage, is presented. Active bleeding occurs in the first hours after symptom onset, with early neurologic deterioration. Identifying those patients who are more likely to have hematoma expansion is an active area of research, and there are many ongoing therapeutic trials targeting this specific patient population at risk. PMID:27432674

  2. Epizootic hemorrhagic disease in a yak

    PubMed Central

    Raabis, Sarah M.; Byers, Stacey R.; Han, Sushan; Callan, Robert J.

    2014-01-01

    Epizootic hemorrhagic disease virus (EHDV) infection was diagnosed in a 3-year-old yak. The yak had signs of intermittent tremors, dysphagia, oral ulcerative lesions, hemorrhagic enteritis, tachypnea, and thrombocytopenia. Postmortem diagnostics confirmed EHDV (serotype 2) using reverse-transcriptase polymerase chain reaction (RT-PCR). Gross and histopathological results were consistent with EHDV reported in other species. PMID:24688138

  3. Epizootic hemorrhagic disease in yaks (Bos grunniens).

    PubMed

    Van Campen, Hana; Davis, Charlie; Flinchum, John D; Bishop, Jeanette V; Schiebel, Anita; Duncan, Colleen; Spraker, Terry

    2013-05-01

    An epizootic of hemorrhagic disease associated with Epizootic hemorrhagic disease virus serotype 2 (EHDV-2) infections in yaks from 5 herds occurred in Colorado between August 21 and October 3, 2012. Affected yaks presented with fever, lethargy, anorexia, dyspnea, and swollen conjunctivae. Ulcerated dental pads, mucoid sanguineous nasal discharge, petechial hemorrhages in multiple organs, pulmonary edema, and serosanguinous fluid in the thorax, abdomen, and pericardial sac were observed at necropsy. Blood and tissue samples from 8 yaks with similar clinical signs and necropsy findings were positive for EHDV-2 by reverse transcription polymerase chain reaction and 5 yaks were seropositive for EHDV. Tests for malignant catarrhal fever (Ovine herpesvirus 2), Bovine viral diarrhea virus, Bovine herpesvirus 1, Foot-and-mouth disease virus, and Vesicular stomatitis virus were negative. The findings indicate that yaks are susceptible to infection with EHDV-2 and exhibit the clinical signs, and gross and histologic lesions of hemorrhagic disease observed in other ruminant species. PMID:23572453

  4. Epizootic hemorrhagic disease in Alberta, Canada.

    PubMed

    Pybus, Margo J; Ravi, Madhu; Pollock, Colleen

    2014-07-01

    Epizootic hemorrhagic disease (EHD) virus serotype 2 was identified by reverse-transcription (RT)-PCR in a white-tailed deer (Odocoileus virginianus) found dead in southern Alberta in September 2013. Field observations indicate at least 50 deer, primarily white-tailed deer, and three pronghorn antelope (Antilocapra americana) died during a suspected localized EHD outbreak. PMID:24807363

  5. Crohn's disease presenting as acute gastrointestinal hemorrhage

    PubMed Central

    Podugu, Amareshwar; Tandon, Kanwarpreet; Castro, Fernando J

    2016-01-01

    Severe gastrointestinal (GI) hemorrhage is a rare complication of Crohn’s disease (CD). Although several surgical and non-surgical approaches have been described over the last 2 decades this complication still poses significant diagnostic and therapeutic challenges. Given the relative infrequency of severe bleeding in CD, available medical literature on this topic is mostly in the form of retrospective case series and reports. In this article we review the risk factors, diagnostic modalities and treatment options for the management of CD presenting as GI hemorrhage. PMID:27122659

  6. [Pulmonary hemorrhage associated with celiac disease].

    PubMed

    Testa, María Eugenia; Maffey, Alberto; Colom, Alejandro; Agüero, Luis; Rogé, Ignacio; Andrewartha, María Sol; Teper, Alejandro

    2012-08-01

    Idiopathic pulmonary hemosiderosis is a severe and potentially fatal disease characterized by recurrent episodes of alveolar hemorrhage, hemoptysis, and anemia. His association with celiac disease, described as Lane- Hamilton syndrome, could be due to the fact that both entities share a common pathogenic immune pathway. We report two patients of 13 years who consulted for hemoptysis and severe anemia that had not responded to immunosuppressive treatment with pulses of methyl prednisolone, oral meprednisone and hydroxychloroquine. Although both children highlight the absence of gastrointestinal symptoms at the time of consultation, the dosage of anti-endomysial and anti-transglutaminase antibodies was positive and biopsy confirmed the presence of intestinal enteropathy. It is emphasized that in patients with diffuse alveolar hemorrhage, even in the absence of gastrointestinal symptoms, the concomitant presence of celiac disease should be evaluated. If celiac disease is present, the incorporation of a gluten-free diet helps to control the symptoms, allows reducing the immunosuppressive treatment and improves the clinical course of both entities. PMID:22859336

  7. Spontaneous labyrinthine hemorrhage in sickle cell disease.

    PubMed

    Whitehead, R E; MacDonald, C B; Melhem, E R; McMahon, L

    1998-09-01

    We report the clinical and MR imaging findings in two African-American patients with manifestations of sickle cell disease affecting the inner ear. Both suffered sudden-onset sensorineural hearing loss and vestibular symptoms, and both had high labyrinthine signal on T1-weighted MR images attributed to labyrinthine hemorrhage. Follow-up studies of the first patient revealed a decrease in abnormal vestibular signal. Careful attention to the labyrinth on T1-weighted MR images can reveal vestibulocochlear clinical findings in sickle cell patients, with important implications for management and prognosis. PMID:9763373

  8. Use of Oligonucleotide Microarrays for Rapid Detection and Serotyping of Acute Respiratory Disease-Associated Adenoviruses

    PubMed Central

    Lin, Baochuan; Vora, Gary J.; Thach, Dzung; Walter, Elizabeth; Metzgar, David; Tibbetts, Clark; Stenger, David A.

    2004-01-01

    The cessation of the adenovirus vaccination program for military trainees has resulted in several recent acute respiratory disease (ARD) outbreaks. In the absence of vaccination, rapid detection methods are necessary for the timely implementation of measures to prevent adenovirus transmission within military training facilities. To this end, we have combined a fluorogenic real-time multiplex PCR assay with four sets of degenerate PCR primers that target the E1A, fiber, and hexon genes with a long oligonucleotide microarray capable of identifying the most common adenovirus serotypes associated with adult respiratory tract infections (serotypes 3, 4, 7, 16, and 21) and a representative member of adenovirus subgroup C (serotype 6) that is a common cause of childhood ARD and that often persists into adulthood. Analyses with prototype strains demonstrated unique hybridization patterns for representative members of adenovirus subgroups B1, B2, C, and E, thus allowing serotype determination. Microarray-based sensitivity assessments revealed lower detection limits (between 1 and 100 genomic copies) for adenovirus serotype 4 (Ad4) and Ad7 cell culture lysates, clinical nasal washes, and throat swabs and purified DNA from clinical samples. When adenovirus was detected from coded clinical samples, the results obtained by this approach demonstrated an excellent concordance with those obtained by the more established method of adenovirus identification as well as by cell culture with fluorescent-antibody staining. Finally, the utility of this method was further supported by its ability to detect adenoviral coinfections, contamination, and, potentially, recombination events. Taken together, the results demonstrate the usefulness of the simple and rapid diagnostic method developed for the unequivocal identification of ARD-associated adenoviral serotypes from laboratory or clinical samples that can be completed in 1.5 to 4.0 h. PMID:15243087

  9. Ischemic and hemorrhagic moyamoya disease in adults: CT findings

    PubMed Central

    Xie, Anming; Luo, Li; Ding, Yaojun; Li, Gongjie

    2015-01-01

    Objective: To investigate the findings of adult moyamoya disease (MD) of different types on plain CT, brain perfusion CT (CTP) and brain CT angiography (CTA). Materials and methods: A total of 48 patients with ischemic MD and hemorrhagic MD were recruited into present study, and findings were collected from plain CT, CTP and CTA. Results: The incidence of watershed or cortex stroke in ischemic MD (55.6% and 38.9%) was higher than in hemorrhagic MD (0%). The incidence of ventricle or basal ganglia stroke in hemorrhagic MD (40.0%, 43.3%) was higher than in ischemic MD (0%, 5.6%). CTP showed hypoperfusion in 11 patients, hyperperfusion in 12 and normal perfusion in 25. Ischemic MD patients were more likely to present hypoperfusion (61.1%; normal perfusion: 22.2%; hyperperfusion: 16.7%). Hemorrhagic MD patients were more likely to present normal perfusion (70%; hyperperfusion: 30%; hypoperfusion: 0%). The incidence of grade II MD in ischemic MD (27.8%) was higher than in hemorrhagic MD (6.7%). The incidences of grade IV and V MD in hemorrhagic MD (33.3% and 16.7%) were higher than in ischemic MD (16.7% and 11.0%). Conclusion: Hemorrhagic MD is dominant in adults with MD and stroke of these patients mainly occurs at the intraventricular space and basal ganglia. Ischemic MD in adults is characterized by hypoperfusion and hemorrhagic MD by normal perfusion on CTP. MD in adults is usually classified as grade II, III or IV on CTA. PMID:26885076

  10. Innocent blood: a history of hemorrhagic disease of the newborn.

    PubMed

    Obladen, Michael

    2015-01-01

    Hemorrhages occurring in the newborn without trauma have been observed by obstetricians since the 17th century, but have been considered different diseases depending on their location. Umbilical hemorrhage associated with obstructed bile canals was described by Cheyne in 1802. Grandidier in 1871 and Townsend in 1894 grouped together various forms of neonatal bleeds and associated them with disturbed coagulation. When the clotting system became better understood in the last decade of the 19th century, effective symptomatic treatment was developed: gelatin, serum injection, and the transfusion of fresh blood. In 1935, Dam detected the function of vitamin K in the coagulation system and 4 years later, Waddell introduced vitamin K administration into therapy and prevention of neonatal hemorrhagic disease. Kernicterus occurred when high doses of synthetic water-soluble vitamin K analogues were given to preterm infants, reminding physicians that progress in neonatal therapy rests on the cornerstones of controlled trials and follow-up. PMID:25678347

  11. Coagulopathy Due to Celiac Disease Presenting as Intramuscular Hemorrhage

    PubMed Central

    Cumbler, Ethan U.; Triebling, Andrzej T.

    2007-01-01

    Introduction Celiac sprue most commonly presents with steatorrhea, abdominal pain, and weight loss. Celiac disease is now becoming more recognized for its atypical presentations. Anemia, osteoporosis, and childhood failure to thrive have been widely discussed. Objective In this paper, we present a case of nontraumatic intramuscular hemorrhage associated with prolongation of both prothrombin time and activated partial thromboplastin time. Main Results Coagulopathy, unmasked by the use of a nonsteroidal anti-inflammatory drug, was found to be attributable to vitamin K deficiency associated with malabsorption of multiple fat soluble vitamins. Celiac sprue was confirmed by small bowel biopsy. A review of the literature finds that, whereas asymptomatic prolongation of coagulation is relatively common in celiac sprue, clinical bleeding is a rare but described presentation. Conclusion This case emphasizes the importance of recognizing hemorrhage as an atypical manifestation of celiac disease and offers the opportunity to review the clinical and laboratory evaluation of a patient who presents with unexplained hemorrhage. PMID:17768663

  12. A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors

    PubMed Central

    Farrow, Anitra L.; Peng, Binghao J.; Gu, Linlin; Krendelchtchikov, Alexandre; Matthews, Qiana L.

    2016-01-01

    Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi’s amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the “Antigen Capsid-Incorporation” strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease. PMID:26978385

  13. A Novel Vaccine Approach for Chagas Disease Using Rare Adenovirus Serotype 48 Vectors.

    PubMed

    Farrow, Anitra L; Peng, Binghao J; Gu, Linlin; Krendelchtchikov, Alexandre; Matthews, Qiana L

    2016-03-01

    Due to the increasing amount of people afflicted worldwide with Chagas disease and an increasing prevalence in the United States, there is a greater need to develop a safe and effective vaccine for this neglected disease. Adenovirus serotype 5 (Ad5) is the most common adenovirus vector used for gene therapy and vaccine approaches, but its efficacy is limited by preexisting vector immunity in humans resulting from natural infections. Therefore, we have employed rare serotype adenovirus 48 (Ad48) as an alternative choice for adenovirus/Chagas vaccine therapy. In this study, we modified Ad5 and Ad48 vectors to contain T. cruzi's amastigote surface protein 2 (ASP-2) in the adenoviral early gene. We also modified Ad5 and Ad48 vectors to utilize the "Antigen Capsid-Incorporation" strategy by adding T. cruzi epitopes to protein IX (pIX). Mice that were immunized with the modified vectors were able to elicit T. cruzi-specific humoral and cellular responses. This study indicates that Ad48-modified vectors function comparable to or even premium to Ad5-modified vectors. This study provides novel data demonstrating that Ad48 can be used as a potential adenovirus vaccine vector against Chagas disease. PMID:26978385

  14. Ebola and Marburg Hemorrhagic Fevers: Neglected Tropical Diseases?

    PubMed Central

    MacNeil, Adam; Rollin, Pierre E.

    2012-01-01

    Ebola hemorrhagic fever (EHF) and Marburg hemorrhagic fever (MHF) are rare viral diseases, endemic to central Africa. The overall burden of EHF and MHF is small in comparison to the more common protozoan, helminth, and bacterial diseases typically referred to as neglected tropical diseases (NTDs). However, EHF and MHF outbreaks typically occur in resource-limited settings, and many aspects of these outbreaks are a direct consequence of impoverished conditions. We will discuss aspects of EHF and MHF disease, in comparison to the “classic” NTDs, and examine potential ways forward in the prevention and control of EHF and MHF in sub-Saharan Africa, as well as examine the potential for application of novel vaccines or antiviral drugs for prevention or control of EHF and MHF among populations at highest risk for disease. PMID:22761967

  15. Mouse adenovirus type 1 causes a fatal hemorrhagic encephalomyelitis in adult C57BL/6 but not BALB/c mice.

    PubMed Central

    Guida, J D; Fejer, G; Pirofski, L A; Brosnan, C F; Horwitz, M S

    1995-01-01

    Mouse adenovirus type 1 (MAV-1) produces a lethal disease in newborn or suckling mice characterized by infectious virus and viral lesions in multiple organs. Previous reports of MAV-1 infection of adult mice generally described serologic evidence of infection without morbidity or mortality. However, our current results demonstrate that MAV-1 causes a fatal illness in adult C57BL/6(B6) mice (50% lethal dose, [LD50], 10(3.0) PFU) but not in adult BALB/c mice at all of the doses tested (LD50, > or = 10(5.0) PFU). Adult (BALB/c x B6)F1 mice were intermediately susceptible (LD50, 10(4.5) PFU). Clinically, the sensitive B6 mice showed symptoms of acute central nervous system (CNS) disease, including tremors, seizures, ataxia, and paralysis. Light microscopic examination of CNS tissue from the B6 animals revealed petechial hemorrhages, edema, neovascularization, and mild inflammation in the brain and spinal cord. Analysis by electron microscopy showed evidence of inflammation, such as activated microglia, as well as swollen astrocytic endfeet and perivascular lipid deposition indicative of blood-brain barrier dysfunction. Outside of the CNS, the only significant pathological findings were foci of cytolysis in the splenic white pulp. Assessment of viral replication from multiple tissues was performed by using RNase protection assays with an antisense MAV-1 early region 1a probe. The greatest amounts of viral mRNA in MAV-1-infected B6 animals were located in the brain and spinal cord. Less viral message was detected in the spleen, lungs, and heart. No viral mRNA was detected in BALB/c mouse tissue, with the exception of low levels in the heart. Viral titers of organ tissues were also determined and were concordant with RNase protection findings on the brain and spinal cord but failed to demonstrate significant infectious virus in additional organs. Our experiments demonstrate that MAV-1 has a striking tropism for the CNS that is strain dependent, and this provides an

  16. An adenovirus linked to mortality and disease in long-tailed ducks (Clangula hyemalis) in Alaska

    USGS Publications Warehouse

    Hollmén, Tuula E.; Franson, J.C.; Flint, P.L.; Grand, J.B.; Lanctot, Richard B.; Docherty, D.E.; Wilson, H.M.

    2003-01-01

    An adenovirus was isolated from intestinal samples of two long-tailed ducks (Clangula hyemalis) collected during a die-off in the Beaufort Sea off the north coast of Alaska in 2000. The virus was not neutralized by reference antiserum against known group I, II, or III avian adenoviruses and may represent a new serotype. The prevalence of the virus was determined in live-trapped long-tailed ducks at the mortality site and at a reference site 100 km away where no mortality was observed. Prevalence of adenovirus antibodies in serum samples at the mortality site was 86% compared to 10% at the reference site. Furthermore, 50% of cloacal swabs collected at the mortality site and only 7% of swabs from the reference site were positive for adenoviruses. In 2001, no mortality was observed at either of the study areas, and virus prevalence in both serum and cloacal samples was low, providing further evidence that the adenovirus was linked to the mortality event in 2000. The virus was used to infect long-tailed ducks under experimental conditions and resulted in lesions previously described for avian adenovirus infections and similar to those observed in long-tailed duck carcasses from the Beaufort Sea. The status of long-tailed ducks has recently become a concern in Alaska due to precipitous declines in breeding populations there since the mid-1970s. Our findings suggest that the newly isolated adenovirus is a disease agent and source of mortality in long-tailed ducks, and thus could be a contributing factor in population declines.

  17. Evidence for the role of a human intestinal adenovirus in the pathogenesis of coeliac disease.

    PubMed Central

    Kagnoff, M F; Paterson, Y J; Kumar, P J; Kasarda, D D; Carbone, F R; Unsworth, D J; Austin, R K

    1987-01-01

    We previously noted a region of amino acid sequence homology between A-gliadin, a major alpha-gliadin component known to activate coeliac disease, and the early region E1b protein of human adenovirus serotype 12 (Ad12), an adenovirus isolated from the human intestinal tract. In the present study sera from coeliac disease patients from the United Kingdom and the United States were assayed for neutralising antibody to Ad12 as evidence of past exposure to that virus and for antibody to synthetic peptides of A-gliadin from the region of shared sequence with the Ad12 E1b protein. Eighty nine per cent of untreated coeliac disease patients had evidence of previous Ad12 infection. There was also a significant increase in the prevalence of neutralising antibody to Ad12 among treated adults (33.3%) and children (30.8%) with coeliac disease compared with controls (0-12.8%) in the western USA and in London. There was no evidence for an increased prevalence of infection with a closely related adenovirus, adenovirus 18, or another enteric virus, Echovirus 11, among coeliac disease subjects. Additional studies documented that a region of A-gliadin that shares amino acid sequence homology with the adenovirus 12 E1b protein could be recognised as an antigenic determinant in active coeliac disease patients. Taken together, these data are compatible with the hypothesis that a viral protein may play a role in the pathogenesis of coeliac disease, perhaps by virtue of immunological cross reactivity between antigenic determinants shared by the viral protein and alpha-gliadins. PMID:2822550

  18. Adenovirus serotype 5 vectored foot-and-mouth disease subunit vaccines: the first decade

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Here we present the results of the first decade of development of a replication-defective human adenovirus (Ad5) containing the capsid and 3C protease coding regions of foot-and-mouth disease virus (FMDV) as a vaccine candidate. In proof-of concept studies we demonstrated that a single inoculation w...

  19. [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

  20. Outbreak of rabbit hemorrhagic disease in domestic lagomorphs.

    PubMed

    Campagnolo, Enzo R; Ernst, Mark J; Berninger, Mary L; Gregg, Douglas A; Shumaker, Thomas J; Boghossian, Aida M

    2003-10-15

    Rabbit hemorrhagic disease (RHD) was diagnosed in domestic lagomorphs on a rabbit farm in Illinois. Clinical signs of RHD in affected rabbits included signs of depression, anorexia, fever, paddling, convulsions, and sudden death. Findings of necropsies and histologic evaluations of specimens of liver and spleen were indicative of RHD. In liver specimens obtained from dead rabbits, RHD viral antigen was detected via hemagglutination assay and viral antigen-detection ELISA. The source of the outbreak was traced to a rabbitry in Utah. As the disease spread, the outbreak involved rabbits in various regions of the United States; > 4,800 rabbits were euthanatized and buried as a result of the depopulation effort in several states. The economic impact of the disease can be considerable; if the disease is suspected, it is imperative that the appropriate state or federal veterinarian's office be contacted immediately. PMID:14584745

  1. Vaccines for prevention of bluetongue and epizootic hemorrhagic disease in livestock: A North American perspective

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bluetongue (BT) and epizootic hemorrhagic disease (EHD) are non-contagious, insect transmitted diseases of domestic and wild ruminants caused by related but distinct viruses. Both BT (BTV) and EHD (EHDV) viruses cause hemorrhagic fevers in susceptible ruminants; however BT is principally a disease o...

  2. Generation of virus like particles for epizootic hemorrhagic disease virus.

    PubMed

    Forzan, Mario; Maan, Sushila; Mazzei, Maurizio; Belaganahalli, Manjunatha N; Bonuccelli, Lucia; Calamari, Monica; Carrozza, Maria Luisa; Cappello, Valentina; Di Luca, Mariagrazia; Bandecchi, Patrizia; Mertens, Peter P C; Tolari, Francesco

    2016-08-01

    Epizootic hemorrhagic disease virus (EHDV) is a distinct species within the genus Orbivirus, within the family Reoviridae. The epizootic hemorrhagic disease virus genome comprises ten segments of linear, double stranded (ds) RNA, which are packaged within each virus particle. The EHDV virion has a three layered capsid-structure, generated by four major viral proteins: VP2 and VP5 (outer capsid layer); VP7 (intermediate, core-surface layer) and VP3 (innermost, sub-core layer). Although EHDV infects cattle sporadically, several outbreaks have recently occurred in this species in five Mediterranean countries, indicating a potential threat to the European cattle industry. EHDV is transmitted by biting midges of the genus Culicoides, which can travel long distances through wind-born movements (particularly over water), increasing the potential for viral spread in new areas/countries. Expression systems to generate self-assembled virus like particles (VLPs) by simultaneous expression of the major capsid-proteins, have been established for several viruses (including bluetongue virus). This study has developed expression systems for production of EHDV VLPs, for use as non-infectious antigens in both vaccinology and serology studies, avoiding the risk of genetic reassortment between vaccine and field strains and facilitating large scale antigen production. Genes encoding the four major-capsid proteins of a field strain of EHDV-6, were isolated and cloned into transfer vectors, to generate two recombinant baculoviruses. The expression of these viral genes was assessed in insect cells by monitoring the presence of specific viral mRNAs and by western blotting. Electron microscopy studies confirmed the formation and purification of assembled VLPs. PMID:27473984

  3. Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FM...

  4. [Hyphema with secondary hemorrhage: think about sickle cell disease].

    PubMed

    Karim, A; Laghmari, M; Dahreddine, M; Guedira, K; Ibrahimy, W; Essakali, N; Mohcine, Z

    2004-04-01

    The Authors report a case of a 13-Year-old white child who presented a grade I hyphema, anterior chamber inflammation after trauma. He presented a secondary hemorrhage with increased intraocular pressure that was not controlled within 48 h, thus requiring surgical intervention. A hemoglobin electrophoresis and hemostasis test showed a sickle cell trait. After hemorrhage resorption, the ocular fundus showed substantial retinal hemorrhage. The final visual outcome was poor and attributed to optic atrophy. Sickle cell trait is a significant risk factor for secondary hemorrhage, increased intraocular pressure, and permanent visual impairement in children who have traumatic hyphemas following blunt trauma. PMID:15173649

  5. Review of Elephant Endotheliotropic Herpesviruses and Acute Hemorrhagic Disease.

    PubMed

    Long, Simon Y; Latimer, Erin M; Hayward, Gary S

    2016-01-01

    More than 100 young captive and wild Asian elephants are known to have died from a rapid-onset, acute hemorrhagic disease caused primarily by multiple distinct strains of two closely related chimeric variants of a novel herpesvirus species designated elephant endotheliotropic herpesvirus (EEHV1A and EEHV1B). These and two other species of Probosciviruses (EEHV4 and EEHV5) are evidently ancient and likely nearly ubiquitous asymptomatic infections of adult Asian elephants worldwide that are occasionally shed in trunk wash secretions. Although only a handful of similar cases have been observed in African elephants, they also have proved to harbor their own multiple and distinct species of Probosciviruses-EEHV2, EEHV3, EEHV6, and EEHV7-found in lung and skin nodules or saliva. For reasons that are not yet understood, approximately 20% of Asian elephant calves appear to be susceptible to the disease when primary infections are not controlled by normal innate cellular and humoral immune responses. Sensitive specific polymerase chain reaction (PCR) DNA blood tests have been developed, routine monitoring has been established, the complete large DNA genomes of each of the four Asian EEHV species have now been sequenced, and PCR gene subtyping has provided unambiguous evidence that this is a sporadic rather than epidemic disease that it is not being spread among zoos or other elephant housing facilities. Nevertheless, researchers have not yet been able to propagate EEHV in cell culture, determine whether or not human antiherpesvirus drugs are effective inhibitors, or develop serology assays that can distinguish between antibodies against the multiple different EEHV species. PMID:26912715

  6. Cellular Changes Induced by Adenovirus Vaccine Vectors Expressing Foot-and-Mouth Disease Virus Structural and Nonstructural Proteins

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) is the most contagious pathogen of cloven-hoofed animals including swine and bovines. The emergency control of outbreaks is dependent on rapid protection and prevention of virus spread. Adenovirus-based FMD subunit vaccines containing the coding region of viral ca...

  7. Molecular evolution of American field strains of bluetongue and epizootic hemorrhagic disease viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recent Orbivirus events in the Americas have been investigated using whole genome amplification and sequencing followed by phylogenetic analysis. These studies utilized an unbiased amplification protocol that allows the whole bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) geno...

  8. A porcine adenovirus with low human seroprevalence is a promising alternative vaccine vector to human adenovirus 5 in an H5N1 virus disease model.

    PubMed

    Patel, Ami; Tikoo, Suresh; Kobinger, Gary

    2010-01-01

    Human adenovirus 5 (AdHu5) vectors are robust vaccine platforms however the presence of naturally-acquired neutralizing antibodies may reduce vector efficacy and potential for re-administration. This study evaluates immune responses and protection following vaccination with a replication-incompetent porcine adenovirus 3 (PAV3) vector as an alternative vaccine to AdHu5 using an avian influenza H5N1 disease model. Vaccine efficacy was evaluated in BALB/c mice following vaccination with different doses of the PAV3 vector expressing an optimized A/Hanoi/30408/2005 H5N1 hemagglutinin antigen (PAV3-HA) and compared with an AdHu5-HA control. PAV3-HA rapidly generated antibody responses, with significant neutralizing antibody titers on day 21, and stronger cellular immune responses detected on day 8, compared to AdHu5-HA. The PAV3-HA vaccine, administered 8 days before challenge, demonstrated improved survival and lower virus load. Evaluation of long-term vaccine efficacy at 12 months post-vaccination showed better protection with the PAV3-HA than with the AdHu5-HA vaccine. Importantly, as opposed to AdHu5, PAV3 vector was not significantly neutralized by human antibodies pooled from over 10,000 individuals. Overall, PAV3-based vector is capable of mediating swift, strong immune responses and offer a promising alternative to AdHu5. PMID:21179494

  9. Five genome sequences of subspecies B1 human adenoviruses associated with acute respiratory disease.

    PubMed

    Dehghan, Shoaleh; Liu, Elizabeth B; Seto, Jason; Torres, Sarah F; Hudson, Nolan R; Kajon, Adriana E; Metzgar, David; Dyer, David W; Chodosh, James; Jones, Morris S; Seto, Donald

    2012-01-01

    Five genomes of human subspecies B1 adenoviruses isolated from cases of acute respiratory disease have been sequenced and archived for reference. These include representatives of two prevalent genomic variants of HAdV-7, i.e., HAdV-7h and HAdV-7d2. The other three are HAdV-3/16, HAdV-16 strain E26, and HAdV-3+7 strain Takeuchi. All are recombinant genomes. Genomics and bioinformatics provide detailed views into the genetic makeup of these pathogens and insight into their molecular evolution. Retrospective characterization of particularly problematic older pathogens such as HAdV-7h (1987) and intriguing isolates such as HAdV-3+7 strain Takeuchi (1958) may provide clues to their phenotypes and serology and may suggest protocols for prevention and treatment. PMID:22158846

  10. Preliminary development of a real-time PCR for all serotypes of Epizootic Hemorrhagic Disease Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epizootic hemorrhagic diseases virus (EHDV) has been associated with bluetongue-like disease in cattle. Although US EHDV strains have not been experimentally proven to cause disease in cattle there is serologic evidence of infection in cattle. Bluetongue virus (BTV) causes an estimated $125,000,00...

  11. Preliminary development of a real-time PCR for all serotypes of Epizootic Hemorrhagic Disease Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epizootic hemorrhagic diseases virus (EHDV) has been associated with bluetongue-like disease in cattle. Although US EHDV strains have not been experimentally proven to cause disease in cattle there is serologic evidence of infection in cattle. Bluetongue virus (BTV) causes an estimated $125,000,000 ...

  12. Molecular detection of two adenoviruses associated with disease in Australian lizards.

    PubMed

    Hyndman, T; Shilton, C M

    2011-06-01

    We give the first published description of the pathology and molecular findings associated with adenovirus infection in lizards in Australia. A central netted dragon (Ctenophorus nuchalis) exhibited severe necrotising hepatitis with abundant intranuclear inclusion bodies within hepatocytes and rarely within intestinal epithelial cells. Polymerase chain reaction (PCR) using pooled tissues yielded an amplicon that shared strong nucleotide identity with an agamid adenovirus (EU914203). PCR on the liver of a bearded dragon (Pogona minor minor) with illthrift, coccidiosis, nematodiasis and hepatic lipidosis yielded an amplicon with strong nucleotide identity to a helodermatid adenovirus (EU914207). PMID:21595645

  13. Molecular evolution of epizootic hemorrhagic disease viruses in North America based on historical isolates

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epizootic hemorrhagic disease virus (EHDV) is an orbivirus of the Reoviridae family that has significant impact on wild and captive white-tailed deer. Although closely related to bluetongue virus (BTV) that can cause disease in sheep and cattle, North American EHDV historically has not been associat...

  14. AN UPDATE OF ADENOVIRAL HEMORRHAGIC DISEASE IN MULE DEER IN CALIFORNIA

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In the summer and fall of 1993, a newly recognized disease, adenoviral hemorrhagic disease, caused widespread mortality in black-tailed (Odocoileus hemionus columbianus) and California mule deer (Odocoileus hemionus californicus) in northern California. Greater than a thousand deer were estimated t...

  15. Genetic characterization of epizootic hemorrhagic disease virus strains isolated from cattle in Israel

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epizootic hemorrhagic disease virus (EHDV), an Orbivirus not previously reported in Israel, was isolated from Israeli cattle during a “bluetongue like” disease outbreak in 2006. To ascertain the origin of this new virus, three isolates from the outbreak were fully sequenced and compared with availab...

  16. A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques

    PubMed Central

    Vatter, Heather A.; Donaldson, Eric F.; Huynh, Jeremy; Rawlings, Stephanie; Manoharan, Minsha; Legasse, Alfred; Planer, Shannon; Dickerson, Mary F.; Lewis, Anne D.; Colgin, Lois M.A.; Axthelm, Michael K.; Pecotte, Jerilyn K.; Baric, Ralph S.; Wong, Scott W.; Brinton, Margo A.

    2014-01-01

    Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100–1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages showed a very high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100 PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques. PMID:25463617

  17. Genomic and Bioinformatics Analysis of HAdV-4, a Human Adenovirus Causing Acute Respiratory Disease: Implications for Gene Therapy and Vaccine Vector Development

    PubMed Central

    Purkayastha, Anjan; Ditty, Susan E.; Su, Jing; McGraw, John; Hadfield, Ted L.; Tibbetts, Clark; Seto, Donald

    2005-01-01

    Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD. PMID:15681456

  18. Genomic and bioinformatics analysis of HAdV-4, a human adenovirus causing acute respiratory disease: implications for gene therapy and vaccine vector development.

    PubMed

    Purkayastha, Anjan; Ditty, Susan E; Su, Jing; McGraw, John; Hadfield, Ted L; Tibbetts, Clark; Seto, Donald

    2005-02-01

    Human adenovirus serotype 4 (HAdV-4) is a reemerging viral pathogenic agent implicated in epidemic outbreaks of acute respiratory disease (ARD). This report presents a genomic and bioinformatics analysis of the prototype 35,990-nucleotide genome (GenBank accession no. AY594253). Intriguingly, the genome analysis suggests a closer phylogenetic relationship with the chimpanzee adenoviruses (simian adenoviruses) rather than with other human adenoviruses, suggesting a recent origin of HAdV-4, and therefore species E, through a zoonotic event from chimpanzees to humans. Bioinformatics analysis also suggests a pre-zoonotic recombination event, as well, between species B-like and species C-like simian adenoviruses. These observations may have implications for the current interest in using chimpanzee adenoviruses in the development of vectors for human gene therapy and for DNA-based vaccines. Also, the reemergence, surveillance, and treatment of HAdV-4 as an ARD pathogen is an opportunity to demonstrate the use of genome determination as a tool for viral infectious disease characterization and epidemic outbreak surveillance: for example, rapid and accurate low-pass sequencing and analysis of the genome. In particular, this approach allows the rapid identification and development of unique probes for the differentiation of family, species, serotype, and strain (e.g., pathogen genome signatures) for monitoring epidemic outbreaks of ARD. PMID:15681456

  19. Vector competence of Culicoides sonorensis (Diptera: Ceratopogonidae) to epizootic hemorrhagic disease virus serotype 7

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Culicoides sonorensis (Diptera: Ceratopogonidae) is a vector of epizootic hemorrhagic disease virus (EHDV) serotypes 1 and 2 in North America, where these viruses are well-known pathogens of white-tailed deer (WTD) and other wild ruminants. Although historically rare, reports of clinica...

  20. Fatal Intramyocardial Hemorrhage After Pericardiotomy in a Patient With von Willebrand Disease.

    PubMed

    Singh, Karen E; Hirsch, Benjamin; Colquhoun, Douglas; Durieux, Marcel

    2016-09-01

    Patients with large pericardial effusions and possible tamponade undergoing general anesthesia for pericardial drainage are generally thought to be at a highest risk of cardiovascular collapse before drainage of the effusion. Here, we report a case of extensive and fatal intramyocardial hemorrhage after drainage of a pericardial effusion in a patient with von Willebrand disease. PMID:27580407

  1. Hereditary cerebral hemorrhage with amyloidosis in patients of Dutch origin is related to Alzheimer disease

    SciTech Connect

    van Duinen, S.G.; Castano, E.M.; Prelli, F.; Bots, G.T.A.B.; Luyendijk, W.; Frangione, B.

    1987-08-01

    Hereditary cerebral hemorrhage with amyloidosis in Dutch patients is an autosomal dominant form of vascular amyloidosis restricted to the leptomeninges and cerebral cortex. Clinically the disease is characterized by cerebral hemorrhages leading to an early death. Immunohistochemical studies of five patients revealed that the vascular amyloid deposits reacted intensely with an antiserum raised against a synthetic peptide homologous to the Alzheimer disease-related ..beta..-protein. Silver stain-positive, senile plaque-like structures were also labeled by the antiserum, yet these lesions lacked the dense amyloid cores present in typical plaques of Alzheimer disease. No neurofibrillary tangles were present. Amyloid fibrils were purified from the leptomeningeal vessels of one patient who clinically had no signs of dementia. The protein had a molecular weight of approx. 4000 and its partial amino acid sequence to position 21 showed homology to the ..beta..-protein of Alzheimer disease and Down syndrome. These results suggest that hereditary cerebral hemorrhage with amyloidosis of Dutch origin is pathogenetically related to Alzheimer disease and support the concept that the initial amyloid deposition in this disorder occurs in the vessel walls before damaging the brain parenchyma. Thus, deposition of ..beta..-protein in brain tissue seems to be related to a spectrum of diseases involving vascular syndromes, progressive dementia, or both.

  2. Serial Lung Magnetic Resonance Imaging to Monitor Disease Progression in a Child With a Diffuse Alveolar Hemorrhage Syndrome

    PubMed Central

    Kaleel, Mohammed; Schramm, Craig; Pascal, Melanie; O’Louglin, Michael; Collins, Melanie Sue

    2015-01-01

    Serial lung magnetic resonance imaging (MRI) was performed in a child with diffuse alveolar hemorrhage (DAH). To minimize radiation exposure with conventional serial chest computerized tomography (CT), serial MRIs of the lungs were used. This effectively monitored her disease process as well as detected acute hemorrhage after 5 years remission. PMID:25699125

  3. Bilateral spontaneous perirenal hemorrhage in an acquired cystic kidney disease hemodialysis patient.

    PubMed

    Hirohama, Daigoro; Miyakawa, Hiroshi

    2012-01-01

    Acquired cystic kidney disease (ACKD) is a well-known late stage complication of chronic kidney disease. Cysts tend to grow with time on dialysis and could lead to malignant transformation, and intra- or perirenal hemorrhage is a rare complication of ACKD. Here we describe one case of bilateral spontaneous perirenal hemorrhage of ACKD in a 44-year-old man, on hemodialysis for 15 years. One was due to cyst rupture, and the other was due to aneurism rupture, both were controlled with transcatheter arterial embolization. In renal arteriography at the second rupture, we demonstrated extravasation from an aneurysm being present at the periphery of right renal artery. Several spontaneous perirenal hemorrhage cases were reported but its clinical information is limited, moreover, bilateral cases were extremely rare. Furthermore, to our knowledge, this is the first report of spontaneous perirenal hemorrhage caused by intraparenchymal renal artery aneurysm rupture in ACKD patients. We report this case because of its rarity and significance with respect to the complication of dialysis patients, review reported bilateral cases, and discuss some clinical characteristics. PMID:24533199

  4. Life-threatening hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in the treatment of hematologic diseases.

    PubMed

    Mori, Minako; Tsunemine, Hiroko; Imada, Kazunori; Ito, Kiminari; Kodaka, Taiichi; Takahashi, Takayuki

    2014-06-01

    Since the late 1990s, Stenotrophomonas maltophilia (S. maltophilia) has become one of the most common nonfermenting Gram-negative bacilli that cause opportunistic infection. Patients with hematologic diseases are the most risky candidate for S. maltophilia pneumonia or sepsis because of chemotherapy-induced neutropenia or immunodeficiency. Frequent exposure to broad-spectrum antibiotics and prolonged insertion of central venous catheter further enhance the risk of S. maltophilia infection. One of the most severe S. maltophilia infections is hemorrhagic pneumonia. This type of infection is mostly fatal because of pulmonary alveolar hemorrhage that leads to acute respiratory failure. Furthermore, S. maltophilia exhibits a high-level intrinsic resistance to conventional antibiotics such as β-lactams and aminoglycosides and, more recently, the increasing acquired resistance to co-trimoxazole and quinolones. According to our experienced and previously reported cases, all of the patients with hemorrhagic pneumonia caused by S. maltophilia had a fatal course within a few days after the onset of the pneumonia. In this article, we perform a systematic review on a total 30 cases of hemorrhagic pneumonia induced by S. maltophilia from our institutions and the literature, and we describe its early diagnosis, prophylaxis, and recommended therapeutic strategy for the infection in the treatment of hematologic disease. PMID:24535696

  5. Characterization of Neutralization Determinants on Epizootic Hemorrhagic Disease Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The control of Rift Valley Fever (RVF) outbreaks requires sensitive and specific diagnostics, effective vector monitoring and management, and vaccination of humans and animals. The Arthropod-Borne Animal Diseases Research Laboratory has a multidisciplinary scientific team comprised of microbiologist...

  6. Wetland cover dynamics drive hemorrhagic disease patterns in white-tailed deer in the United States.

    PubMed

    Berry, Brett S; Magori, Krisztian; Perofsky, Amanda C; Stallknecht, David E; Park, Andrew W

    2013-07-01

    While vector-borne diseases are known to be particularly influenced by environmental factors, the impact of land-cover change on vector-borne wildlife disease patterns is poorly understood, largely due to the paucity of data on disease occurrence at extensive spatial and temporal scales. Widespread and rapid anthropogenic land-cover change, especially urbanization, has transformed the US landscape during the last century. Epizootic hemorrhagic disease virus and blue tongue virus, vectored by Culicoides biting midges, are two RNA viruses in the Orbivirus genus that cause severe hemorrhagic disease (HD) in white-tailed deer (Odocoileus virginianus). We examine the spatial dynamics of HD affecting white-tailed deer in the contiguous United States in two periods covering 1980 to 2007 in connection with land-cover change over the same time. Using spatial statistical modeling, wetland cover emerges as a critical driver of HD morbidity, whereas the drivers of mortality patterns are more complex. Increasing wetland cover is positively associated with HD morbidity, which is consistent with the ecologic requirements of the Culicoides vector. Wetland cover is inherently dynamic due to its importance to biodiversity and water quality as well as its utility for other purposes when drained. Accordingly this analysis helps in understanding the consequences of changing wetlands on vector-borne disease patterns, to identify disease hotspots in a large landscape, and to forecast the spatial spread of HD and related diseases. PMID:23778598

  7. Experimental bluetongue and epizootic hemorrhagic disease virus infection in California black-tailed deer.

    PubMed

    Work, T M; Jessup, D A; Sawyer, M M

    1992-10-01

    Four adult black-tailed deer (Odocoileus hemioneus columbianus) and five fawns were inoculated with bluetongue virus (BTV) and one adult deer was inoculated with epizootic hemorrhagic disease (EHD) virus to produce clinical signs and lesions of hemorrhagic disease. Serologic response was monitored using the agar gel immunodiffusion (AGID) test and the competitive enzyme-linked immunosorbent assay (C-ELISA). Embryonating chicken eggs and vero cells were used to detect viremia. No animal exhibited clinical or pathologic signs of hemorrhagic disease. Bluetongue viremia was detected as early as 2 days post-inoculation (DPI-2) and in some animals, persisted until at least DPI-12. The earliest detection of BTV antibodies using the AGID was DPI-8. Two adult deer remained seropositive for BTV antibodies for > 9 mo and 1 yr, respectively, using both the AGID and C-ELISA tests. We observed cross reactions between BT and EHD antibodies using the AGID tests. Also, the AGID test did not consistently detect exposure to BTV. Viremia was not detected in the deer inoculated with EHD although this animal was AGID positive between DPI-6 and DPI-49. PMID:1335522

  8. Adenovirus vectored vaccines against influenza a virus do not result in vaccine associated enhanced respiratory disease following heterologous challenge in contrast to whole inactivated virus vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Heterologous influenza A virus (IAV) challenge following vaccination with an intramuscular (IM) whole inactivated vaccine (WIV) can result in vaccine-associated enhanced respiratory disease (VAERD). The objective of this study was to use an adenovirus (Ad5) vector vaccine platform that expressed IAV...

  9. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using direct homologous challenge

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularl...

  10. Early detection and visualization of human adenovirus serotype 5-viral vectors carrying foot-and-mouth disease virus or luciferase transgenes in cell lines and bovine tissues

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recombinant replication-defective human adenovirus type 5 (Ad5) vaccines containing capsid-coding regions from foot-and-mouth disease virus (FMDV) have been demonstrated to induce effective immune responses and provide homologous protective immunity against FMDV in cattle. However, basic mechanisms ...

  11. Comparative Pathogenesis of Alkhumra Hemorrhagic Fever and Kyasanur Forest Disease Viruses in a Mouse Model

    PubMed Central

    Sawatsky, Bevan; McAuley, Alexander J.; Holbrook, Michael R.; Bente, Dennis A.

    2014-01-01

    Kyasanur Forest disease virus (KFDV) and Alkhumra hemorrhagic fever virus (AHFV) are genetically closely-related, tick-borne flaviviruses that cause severe, often fatal disease in humans. Flaviviruses in the tick-borne encephalitis (TBE) complex typically cause neurological disease in humans whereas patients infected with KFDV and AHFV predominately present with hemorrhagic fever. A small animal model for KFDV and AHFV to study the pathogenesis and evaluate countermeasures has been lacking mostly due to the need of a high biocontainment laboratory to work with the viruses. To evaluate the utility of an existing mouse model for tick-borne flavivirus pathogenesis, we performed serial sacrifice studies in BALB/c mice infected with either KFDV strain P9605 or AHFV strain Zaki-1. Strikingly, infection with KFDV was completely lethal in mice, while AHFV caused no clinical signs of disease and no animals succumbed to infection. KFDV and high levels of pro-inflammatory cytokines were detected in the brain at later time points, but no virus was found in visceral organs; conversely, AHFV Zaki-1 and elevated levels of cytokines were found in the visceral organs at earlier time points, but were not detected in the brain. While infection with either virus caused a generalized leukopenia, only AHFV Zaki-1 induced hematologic abnormalities in infected animals. Our data suggest that KFDV P9605 may have lost its ability to cause hemorrhagic disease as the result of multiple passages in suckling mouse brains. However, likely by virtue of fewer mouse passages, AHFV Zaki-1 has retained the ability to replicate in visceral organs, cause hematologic abnormalities, and induce pro-inflammatory cytokines without causing overt disease. Given these striking differences, the use of inbred mice and the virus passage history need to be carefully considered in the interpretation of animal studies using these viruses. PMID:24922308

  12. Mutation of the Alzheimer's Disease Amyloid Gene in Hereditary Cerebral Hemorrhage, Dutch Type

    NASA Astrophysics Data System (ADS)

    Levy, Efrat; Carman, Mark D.; Fernandez-Madrid, Ivan J.; Power, Michael D.; Lieberburg, Ivan; van Duinen, Sjoerd G.; Bots, Gerard Th. A. M.; Luyendijk, Willem; Frangione, Blas

    1990-06-01

    An amyloid protein that precipitates in the cerebral vessel walls of Dutch patients with hereditary cerebral hemorrhage with amyloidosis is similar to the amyloid protein in vessel walls and senile plaques in brains of patients with Alzheimer's disease, Down syndrome, and sporadic cerebral amyloid angiopathy. Cloning and sequencing of the two exons that encode the amyloid protein from two patients with this amyloidosis revealed a cytosine-to-guanine transversion, a mutation that caused a single amino acid substitution (glutamine instead of glutamic acid) at position 22 of the amyloid protein. The mutation may account for the deposition of this amyloid protein in the cerebral vessel walls of these patients, leading to cerebral hemorrhages and premature death.

  13. [Hemorrhagic Adult Unilateral Moyamoya Disease with Multiple Unruptured Intracranial Aneurysms: A Case Report].

    PubMed

    Ozaki, Saya; Inoue, Akihiro; Miyazaki, Hajime; Onoue, Shinji; Ichikawa, Haruhisa; Fukumoto, Shinya; Iwata, Shinji; Kohno, Kanehisa

    2016-02-01

    Adult unilateral moyamoya disease with intracranial aneurysm is frequently reported in the literature, but there is much variation in its treatment. In this case report, we describe the time course and treatment regimen of a patient with moyamoya disease and review the literature regarding moyamoya disease with intracranial aneurysm. A 64-year-old man had untreated intracranial aneurysm and unilateral moyamoya disease for 10 years. He presented with sudden-onset right hemiparesis and aphasia due to a subcortical hemorrhage. He was admitted to the local neurosurgical unit, and upon resolution of symptoms, he was admitted to our hospital. A cerebral angiogram revealed the champagne bottleneck sign of the left carotid artery and obliteration of the top of the left intracranial carotid artery with a moyamoya phenomenon. Two unruptured intracranial aneurysms were identified in the anterior communicating artery(Acom A) and the right intracranial carotid artery(C3). We performed superficial temporal artery-middle cerebral artery anastomosis followed by aneurysmal neck clipping of the Acom A aneurysm. Postoperative imaging showed no new ischemic damage and improved cerebral blood flow. Although the patient experienced temporal worsening of aphasia, his function recovered a few months later and he was able to resume his normal daily life activities. The combination of direct bypass surgery and aneurysmal neck clipping might be a therapeutic option for hemorrhagic unilateral moyamoya disease with unruptured intracranial aneurysm. PMID:26856265

  14. Recurrent Bleeding in Hemorrhagic Moyamoya Disease : Prognostic Implications of the Perfusion Status

    PubMed Central

    Jo, Kyung-Il; Kim, Min Soo; Yeon, Je Young; Kim, Jong-Soo

    2016-01-01

    Objective Hemorrhagic moyamoya disease (hMMD) is associated with a poor clinical course. Furthermore, poorer clinical outcomes occur in cases of recurrent bleeding. However, the effect of hemodynamic insufficiency on rebleeding risk has not been investigated yet. This study evaluated the prognostic implications of the perfusion status during the clinical course of adult hMMD. Methods This retrospective study enrolled 52 adult hMMD patients between April 1995 and October 2010 from a single institute. Demographic data, clinical and radiologic characteristics, including hemodynamic status using single photon emission computed tomography (SPECT), and follow up data were obtained via a retrospective review of medical charts and imaging. Statistical analyses were performed to explore potential prognostic factors. Results Hemodynamic abnormality was identified in 44 (84.6%) patients. Subsequent revascularization surgery was performed in 22 (42.3%) patients. During a 58-month (median, range 3–160) follow-up assessment period, 17 showed subsequent stroke (hemorrhagic n=12, ischemic n=5, Actuarial stroke rate 5.8±1.4%/year). Recurrent hemorrhage was associated with decreased basal perfusion (HR 19.872; 95% CI=1.196–294.117) and omission of revascularization (10.218; 95%; CI=1.532–68.136). Conclusion Decreased basal perfusion seems to be associated with recurrent bleeding. Revascularization might prevent recurrent stroke in hMMD by rectifying the perfusion abnormality. A larger-sized, controlled study is required to address this issue. PMID:26962416

  15. Central vestibular disease in a blue and gold macaw (Ara ararauna) with cerebral infarction and hemorrhage.

    PubMed

    Grosset, Claire; Guzman, David Sanchez-Migallon; Keating, M Kelly; Gaffney, Patricia M; Lowenstine, Linda; Zwingenberger, Allison; Young, Alex C; Vernau, Karen M; Sokoloff, Amberly M; Hawkins, Michelle G

    2014-06-01

    A 24-year-old female blue and gold macaw (Ara ararauna) was presented for an acute onset of left head tilt. On examination, the macaw was dehydrated and had a 120-degree left head tilt, decreased proprioception of the left pelvic limb, and intermittent vertical nystagmus. Results of hematologic testing and biochemical analysis revealed severe leukocytosis with lymphopenia and heterophilia and a high uric acid concentration. Radiographs showed bilateral intertarsal joint osteoarthritis and a healed ulnar fracture. Magnetic resonance imaging of the brain revealed focal T2 and fluid-attenuated inversion recovery hyperintense lesions in the right cerebral hemisphere and in the midbrain. The midbrain lesion showed susceptibility artifact on the T2* sequence, suggesting hemorrhage. In the T2* sequence, iron accumulation (as seen with hemorrhage) distorts the magnetic signal, resulting in the production of a susceptibility artifact, which can then be visualized as a region of hypointensity. The bird was hospitalized but died despite intensive care. Necropsy revealed multiple cerebral vascular lesions including an acute cerebral infarct, a ruptured midbrain aneurysm, and multifocal systemic atherosclerosis. To our knowledge, this is the first report of a cerebral aneurysm in a bird. This report correlates the clinical presentation, imaging, and histopathologic findings in a macaw with central vestibular disease and demonstrates how advanced imaging techniques can identify hemorrhagic lesions through the T2* sequence. PMID:25115042

  16. Spatio-temporal patterns of Epizootic Hemorrhagic Disease (EHD) occurrence in the Continental USA (1980-2010)

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Background: Statement of the hypothesis or research question. Epizootic Hemorrhagic Disease (EHD) is a Culicoides insect-borne viral disease of wild and domestic ruminants commonly reported in the USA. While the severity of disease varies by geographic location, mortality rates can be as high as 90...

  17. Epidemiology and transmission characteristics of human adenovirus type 7 caused acute respiratory disease outbreak in military trainees in East China

    PubMed Central

    Cheng, Jun; Qi, Xiaoping; Chen, Dawei; Xu, Xujian; Wang, Guozheng; Dai, Yuzhu; Cui, Dawei; Chen, Qingyong; Fan, Ping; Ni, Liuda; Liu, Miao; Zhu, Feiyan; Yang, Mei; Wang, Changjun; Li, Yuexi; Sun, Changgui; Wang, Zhongyong

    2016-01-01

    Background: Human adenovirus type 7 (HAdV7) is globally attracting great concern as its high morbidity and severity in respiratory diseases, especially in Asia. Objective: To investigate the clinical and epidemiologic characteristics of HAdV7 infection outbreak in East China. Methods: The clinical samples were collected from the patients of an ARD outbreak in East Chinafor the detection of causative pathogens by multiplex PCR. The molecular type of human adenovirus isolates were identified by sequencing and homologous comparison based on their hexon genes. The spatiotemporal dynamics of global HAdV7 was investigated using the phylogenetic and phylogeographic analyses. Total 67 referenced HAdV7 hexon sequences (>800 bp) from GenBank were selected for constructing the maximum likelihood tree by MEGA 5.1.0, grouped according to the tree topology for the further migration analysis by PAUP* 4.0 and MigraPhyla 1.0 b to understand the transmission patterns of HAdV7 in global epidemics. Results: The results showed HAdV7 as the causative pathogen in this outbreak, and the outbreak strains had the hexon sequences highly identical with the isolates in Shaanxi (2012). The origin of HAdV7 was inferred as California, meanwhile a total of 21 migration routes were acquired. HAdV7 in this outbreak was statistically proven dispersed from Shaanxi province (2012). Conclusions: The analyses of epidemiology and transmission pattern of HAdV7 would not only enrich the molecular biological basic database but also provide theoretical basis for HAdV7 prevention and control strategy. PMID:27347341

  18. Comparative analysis of rabbit hemorrhagic disease virus strains originating from outbreaks in the Russian Federation.

    PubMed

    Burmakina, Galina; Malogolovkina, Nina; Lunitsin, Andrey; Titov, Ilya; Tsybanov, Sodnom; Malogolovkin, Alexander

    2016-07-01

    Since the first introduction of rabbit hemorrhagic disease (RHD) in 1986, disease outbreaks have been continuously reported in different regions of Russia. Despite extensive vaccination, sporadic RHD cases are still reported. Here, we examine eleven RHDV strains originating from disease outbreaks occurring between 2003 and 2012 and one widely used vaccine strain. Notable phenotypic and genetic heterogeneity among RHDV strains was observed. The RHDV strains Tambov-2010, Perm-2010, Manihino-09 showed different hemagglutinating activity (HA) at 4 °C and room temperature. While all RHDV field strains were identified as hemagglutinating virulent viruses of the RHDVa variant, the vaccine strain was assigned as a "classical" RHDV. These data indicate that since 2003, RHDVa has become the predominant variant circulating in Russia. PMID:27094306

  19. Co-Circulation of Multiple Hemorrhagic Fever Diseases with Distinct Clinical Characteristics in Dandong, China

    PubMed Central

    Wang, Wen; Zhao, Yong-Xiang; Zhang, Jing-Shan; He, Jin-Rong; Li, Ming-Hui; Zhao, Xue-Hua; Liu, De-Wei; Fu, Xiao-Kang; Tian, Di; Li, Xing-Wang; Xu, Jianguo; Plyusnin, Alexander; Holmes, Edward C.; Zhang, Yong-Zhen

    2014-01-01

    Hemorrhagic fevers (HF) caused by viruses and bacteria are a major public health problem in China and characterized by variable clinical manifestations, such that it is often difficult to achieve accurate diagnosis and treatment. The causes of HF in 85 patients admitted to Dandong hospital, China, between 2011–2012 were determined by serological and PCR tests. Of these, 34 patients were diagnosed with Huaiyangshan hemorrhagic fever (HYSHF), 34 with Hemorrhagic Fever with Renal Syndrome (HFRS), one with murine typhus, and one with scrub typhus. Etiologic agents could not be determined in the 15 remaining patients. Phylogenetic analyses of recovered bacterial and viral sequences revealed that the causative infectious agents were closely related to those described in other geographical regions. As these diseases have no distinctive clinical features in their early stage, only 13 patients were initially accurately diagnosed. The distinctive clinical features of HFRS and HYSHF developed during disease progression. Enlarged lymph nodes, cough, sputum, and diarrhea were more common in HYSHF patients, while more HFRS cases presented with headache, sore throat, oliguria, percussion pain kidney area, and petechiae. Additionally, HYSHF patients displayed significantly lower levels of white blood cells (WBC), higher levels of creations kinase (CK) and alanine aminotransferase (ALT), while HFRS patients presented with an elevation of blood urea nitrogen (BUN) and creatinine (CREA). These clinical features will assist in the accurate diagnosis of both HYSHF and HFRS. Overall, our data reveal the complexity of pathogens causing HFs in a single Chinese hospital, and highlight the need for accurate early diagnosis and a better understanding of their distinctive clinical features. PMID:24587107

  20. Host and Potential Vector Susceptibility to an Emerging Orbivirus in the United States: Epizootic Hemorrhagic Disease Virus Serotype 6

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epizootic hemorrhagic disease (EHD) viruses (EHDV) are orbiviruses transmitted by Culicoides biting midges to domestic and wild ruminants. EHDV-1 and -2 are enzootic in the U.S., where EHD is the most significant viral disease of white-tailed deer (WTD; Odocoileus virginianus) and reports of EHD in ...

  1. Draft Genome Sequences of Two Pasteurella multocida Strains Isolated from Buffaloes in India with Hemorrhagic Septicemia Disease

    PubMed Central

    Abrahante, J. E.; Veeregowda, B. M.; Hogtapur, S. S.; Briggs, R. E.; Maheswaran, S. K.

    2014-01-01

    Pasteurella multocida serotype B:2 is the causative agent of hemorrhagic septicemia in cattle and buffaloes in Asia. It is an acute fatal disease and is considered one of the most economically important diseases in this region of the world. We present here the draft genome sequences of strains 2213 and 3213 of P. multocida. PMID:25103770

  2. Transmission and epidemiology of bluetongue and epizootic hemorrhagic disease in North America: current perspectives, research gaps, and future directions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) are arthropod-transmitted viruses in the genus Orbivirus of the family Reoviridae. These viruses infect a variety of domestic and wild ruminant hosts, although the susceptibility to clinical disease associated with BTV or EHDV inf...

  3. Partial Sequence of a Novel Virus Isolated from Pelodiscus sinensis Hemorrhagic Disease.

    PubMed

    Liu, Li; Cao, Zheng; Lin, Feng; Ye, Xue-ping; Xu, Yi

    2015-01-01

    Outbreaks of hemorrhagic syndrome-like disease with high mortality rates have frequently occurred in Pelodiscus sinensis farms. The purpose of this study was to investigate the pathogen through challenge infection assays and partial sequencing of the genome of the pathogen. A 453-bp amplicon was obtained by random PCR using the nucleic acid extracted from the tissue homogenate filtrate and showed 32% identity at the amino acid level with the replicase polyprotein of the porcine reproductive and respiratory syndrome virus by Blastx. Multiple alignments indicated the putative protein sequence has some similarities to the replicase polyprotein of Arteriviridae, and the phylogenetic tree showed it was closely related to equine arteritis virus. This sequence was found in the lung of the diseased P. sinensis by in situ hybridization. Dot blot hybridization and quantitative RT-PCR showed that the lung had the highest content of virus. The peak replication of P. sinensis hemorrhagic syndrome virus (TSHSV) in the lung occurred 4 days after infection. The ribonucleic nature of the viral genome was confirmed by RNase A or DNase I treatments. We named the virus TSHSV in this study as P. sinensis is also known as Trionyx sinensis. These results provide a fundamental basis for further understanding the biology and the molecular mechanisms of TSHSV. PMID:26279281

  4. Apparent increase of reported hemorrhagic disease in the midwestern and northeastern USA.

    PubMed

    Stallknecht, David E; Allison, Andrew B; Park, Andrew W; Phillips, Jamie E; Goekjian, Virginia H; Nettles, Victor F; Fischer, John R

    2015-04-01

    We investigated temporal and spatial trends in reporting of hemorrhagic disease (HD) in the midwestern and northeastern US using a 33-yr (1980-2012) questionnaire-based data set. This data set was supported by an additional 19 yr (1994-2012) of bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) isolation results from clinically affected white-tailed deer (Odocoileus virginianus) in these regions. Both the number of counties that were reported positive for HD and the northern latitudinal range of reported HD increased with time. A similar increase was observed with both the number of states annually reporting HD and the number of counties where HD was reported. Large-scale outbreaks occurred in 1988, 1996, 2007, and 2012, and the scale of these individual outbreaks also increased with time. The predominant virus isolated from these regions was EHDV-2, but the prevalence of EHDV-6, which was first detected in 2006, appears to be increasing. Temporally, the extent of regional HD reporting was correlated with regional drought conditions. The significance of increases in reported HD and the incursions and establishment of new BTV and EHDV in the US currently are unknown. PMID:25588003

  5. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, C.W.; Mangel, W.F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  6. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  7. Poly ICLC increases the potency of a replication-defective human adenovirus vectored foot-and-mouth disease vaccine.

    PubMed

    Diaz-San Segundo, Fayna; Dias, Camila C; Moraes, Mauro P; Weiss, Marcelo; Perez-Martin, Eva; Salazar, Andres M; Grubman, Marvin J; de los Santos, Teresa

    2014-11-01

    Foot-and-mouth disease virus (FMDV) causes a highly contagious disease of cloven-hoofed animals. We have previously demonstrated that a replication-defective human adenovirus 5 vector carrying the FMDV capsid coding region of serotype A24 Cruzeiro (Ad5-CI-A24-2B) protects swine and cattle against FMDV challenge by 7 days post-vaccination. However, since relatively large amounts of Ad5-CI-A24-2B are required to induce protection this strategy could be costly for livestock production. Poly ICLC is a synthetic double stranded RNA that activates multiple innate and adaptive immune pathways. In this study, we have tested for the first time, the adjuvant effect of poly ICLC in combination with Ad5-CI-A24-2B in swine. We found that the combination resulted in a reduction of the vaccine protective dose by 80-fold. Interestingly, the lowest dose of Ad5-CI-A24-2B plus 1mg of poly ICLC protected animals against challenge even in the absence of detectable FMDV-specific neutralizing antibodies at the time of challenge. PMID:25216089

  8. Massive pulmonary hemorrhage in enterovirus 71-infected hand, foot, and mouth disease

    PubMed Central

    Lee, Dong Seong; Lee, Young Il; Ahn, Jeong Bae; Kim, Mi Jin; Kim, Jae Hyun; Kim, Nam Hee; Hwang, Jong Hee; Kim, Dong Wook; Lee, Chong Guk

    2015-01-01

    Hand, foot, and mouth disease (HFMD) is an acute, mostly self-limiting infection. Patients usually recover without any sequelae. However, a few cases are life threatening, especially those caused by enterovirus 71 (EV71). A 12-month-old boy was admitted to a primary hospital with high fever and vesicular lesions of the mouth, hands, and feet. After 3 days, he experienced 3 seizure episodes and was referred to our hospital. On admission, he was conscious and his chest radiograph was normal. However, 6 hours later, he suddenly lost consciousness and had developed a massive pulmonary hemorrhage that continued until his death. He experienced several more intermittent seizures, and diffuse infiltration of both lung fields was observed on chest radiography. Intravenous immunoglobulin, dexamethasone, cefotaxime, leukocyte-depleted red blood cells, fresh frozen plasma, inotropics, vitamin K, and endotracheal epinephrine were administered. The patient died 9 hours after intubation, within 3 days from fever onset. EV71 subgenotype C4a was isolated retrospectively from serum and nasopharyngeal swab by real-time reverse transcription-polymerase chain reaction. Here, we report a fatal case of EV71-associated HFMD with sudden-onset massive pulmonary hemorrhage and suspected encephalitis. PMID:25861335

  9. Massive pulmonary hemorrhage in enterovirus 71-infected hand, foot, and mouth disease.

    PubMed

    Lee, Dong Seong; Lee, Young Il; Ahn, Jeong Bae; Kim, Mi Jin; Kim, Jae Hyun; Kim, Nam Hee; Hwang, Jong Hee; Kim, Dong Wook; Lee, Chong Guk; Song, Tae Won

    2015-03-01

    Hand, foot, and mouth disease (HFMD) is an acute, mostly self-limiting infection. Patients usually recover without any sequelae. However, a few cases are life threatening, especially those caused by enterovirus 71 (EV71). A 12-month-old boy was admitted to a primary hospital with high fever and vesicular lesions of the mouth, hands, and feet. After 3 days, he experienced 3 seizure episodes and was referred to our hospital. On admission, he was conscious and his chest radiograph was normal. However, 6 hours later, he suddenly lost consciousness and had developed a massive pulmonary hemorrhage that continued until his death. He experienced several more intermittent seizures, and diffuse infiltration of both lung fields was observed on chest radiography. Intravenous immunoglobulin, dexamethasone, cefotaxime, leukocyte-depleted red blood cells, fresh frozen plasma, inotropics, vitamin K, and endotracheal epinephrine were administered. The patient died 9 hours after intubation, within 3 days from fever onset. EV71 subgenotype C4a was isolated retrospectively from serum and nasopharyngeal swab by real-time reverse transcription-polymerase chain reaction. Here, we report a fatal case of EV71-associated HFMD with sudden-onset massive pulmonary hemorrhage and suspected encephalitis. PMID:25861335

  10. Moyamoya disease manifested as multiple simultaneous intracerebral hemorrhages: A case report and literature review

    PubMed Central

    Yu, Jinlu; Yuan, Yongjie; Li, Wei; Xu, Kan

    2016-01-01

    Multiple simultaneous intracerebral hemorrhages (MSIH) caused by Moyamoya disease (MMD) is extremely rare. To date, the clinical manifestations, imaging characteristics and mechanism of MMD-induced MSIH have not yet been elucidated. In order to improve the understanding on such cases, the present study described a rare case of MSIH caused by MMD. A 40-year-old female patient with no history of hypertension or diabetes mellitus experienced a sudden headache followed by coma. Cranial computed tomography (CT) examination revealed MSIH in the left frontal area, temporal lobe and basal ganglia. CT angiography and digital subtraction angiography examinations revealed typical characteristics of MMD. Subsequent to excluding disorders of the blood system and blood coagulation, we concluded that the present case of MSIH was caused by MMD. Hematoma evacuation and decompressive craniectomy were performed with satisfactory results. In addition, after reviewing previous MSIH cases in the literature, potential mechanisms of MMD-mediated MSIH were considered. In conclusion, MMD should be considered as a possible cause of MSIH during diagnosis and treatment. MMD can lead to pathological changes in the fragility of small arteries; therefore, rupture and hemorrhage at one site may induce a transient increase in blood pressure, causing the rupture of small arteries at other sites, and thus leading to MSIH. Hematoma evacuation and decompression should be conducted in selective cases of MMD-induced MSIH in order to achieve a good prognosis.

  11. The role of human adenoviruses type 41 in acute diarrheal disease in Minas Gerais after rotavirus vaccination

    PubMed Central

    Reis, Thaís Aparecida Vieira; Assis, Andrêssa Silvino Ferreira; do Valle, Daniel Almeida; Barletta, Vívian Honorato; de Carvalho, Iná Pires; Rose, Tatiana Lundgren; Portes, Silvana Augusta Rodrigues; Leite, José Paulo Gagliardi; da Rosa e Silva, Maria Luzia

    2016-01-01

    Human adenovirus species F (HAdV-F) type 40 and 41 are commonly associated with acute diarrheal disease (ADD) across the world. Despite being the largest state in southeastern Brazil and having the second largest number of inhabitants, there is no information in the State of Minas Gerais regarding the role of HAdV-F in the etiology of ADD. This study was performed to determine the prevalence, to verify the epidemiological aspects of infection, and to characterize the strains of human adenoviruses (HAdV) detected. A total of 377 diarrheal fecal samples were obtained between January 2007 and August 2011 from inpatient and outpatient children of age ranging from 0 to 12 years. All samples were previously tested for rotavirus, norovirus, and astrovirus, and 314 of 377 were negative. The viral DNA was extracted, amplified using the polymerase chain reaction and the HAdV-positive samples were sequenced and phylogenetically analyzed. Statistical analyses were performed using the Chi-square test (p < 0.05), considering two conditions: the total of samples tested (377) and the total of negative samples for the remaining viruses tested (314). The overall prevalence of HAdV was 12.47% (47/377); and in 76.60% (36/47) of the positive samples, this virus was the only infectious agent detected. The phylogenetic analysis of partial sequences of 32 positive samples revealed that they all clustered with the HAdV-F type 41. The statistical analysis showed that there was no correlation between the onset of the HAdV infection and the origin of the samples (inpatients or outpatients) in the two conditions tested: the total of samples tested (p = 0.598) and the total of negative samples for the remaining viruses tested (p = 0.614). There was a significant association in the occurrence of infection in children aged 0–12 months for the condition 1 (p = 0.030) as well as condition 2 (p = 0.019). The occurrence of infections due to HAdV did not coincide with a pattern of seasonal

  12. [Hemorrhagic congenital diseases: What can be the future of plasma-derived products against recombinants?].

    PubMed

    Schved, J-F

    2015-08-01

    Until 1990, congenital hemorrhagic disorders were treated by plasma-derived concentrates. The first recombinant drug, recombinant factor VIII was available after this date and few years later recombinant factor IX could also be proposed to patients. The evolution of market share in France was different between these two drugs: while recombinant factor VIII took a large place in hemophilia A treatment (85%), plasma-derived factor IX represent 50% of the French market. In the next years, the arrival of long-acting antihemophilic factors may lead to the dramatically reduce the amount of plasma-derived antihemophilic factors used to treat hemophilia. For rare bleeding coagulation disorders, plasma-derived concentrates are still widely used, while they are the only concentrates available in most diseases. This situation is unlikely to evolve significantly in the next years. PMID:25933512

  13. DEVELOPMENT OF AN ENZYME-LINKED IMMUNOSORBENT ASSAY FOR THE DETECTION OF ANTIBODY TO EPIZOOTIC HEMORRHAGIC DISEASE OF DEER VIRUS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    An enzyme linked immunosorbent assay has been developed to detect antibodies to epizootic hemorrhagic disease of deer virus (EHDV). The assay incorporates a monoclonal antibody to EHDV serotype 2 (EHDV-2) that demonstrates specificity for the viral structural protein, VP7. The assay was evaluated ...

  14. Development of field-deployable instrumentation based on “antigen–antibody” reactions for detection of hemorrhagic disease in ruminants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Development of field-deployable methodology utilizing antigen–antibody reactions and the surface Plasmon resonance (SPR) effect to provide a rapid diagnostic test for recognition of the blue tongue virus (BTV) and epizootic hemorrhage disease virus (EHDV) in wild and domestic ruminants is reported. ...

  15. Susceptibility of white-tailed deer (Odocoileus virginianus) to experimental infection with epizootic hemorrhagic disease virus serotype 7

    Technology Transfer Automated Retrieval System (TEKTRAN)

    During the fall of 2006, in Israel, epizootic hemorrhagic disease virus (EHDV) serotype 7 was the cause of an intense and widespread epizootic in domestic cattle that resulted in significant economic losses for the dairy industry. The susceptibility of potential North American vector and ruminant ho...

  16. Thalidomide-induced hemorrhagic rash in a patient with myelofibrosis and delta-granule storage pool disease.

    PubMed

    Taj, Asma; Abbi, Kamal; Skeel, Roland T

    2015-01-01

    Thalidomide is one of the immunomodulating agents used in current oncology practice. We present a case of hemorrhagic rash induced by thalidomide in a patient with delta granule storage pool disease. The patient was getting thalidomide for underlying myelofibrosis. PMID:24105355

  17. Epizootic hemorrhagic disease virus in captive bison, elk, white-tailed deer, cattle, and goats from Colorado

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A captive wildlife research facility in Fort Collins, Colorado experienced mortality in white-tailed deer (Odocoileus virginianus) due to epizootic hemorrhagic disease virus (EHDV) infection in late summer and early fall of 2007. RNA from EHDV was amplified by RT-PCR from the spleen and lung tissue...

  18. Molecular evolution of epizootic hemorrhagic disease viruses in North America based on historical isolates using motif fingerprints.

    PubMed

    Wilson, W C; Ruder, M G; Jasperson, D; Smith, T P L; Naraghi-Arani, P; Lenhoff, R; Stallknecht, D E; Valdivia-Granda, W A; Sheoran, D

    2016-08-01

    Epizootic hemorrhagic disease virus (EHDV) is an orbivirus of the Reoviridae family that has significant impact on wild and captive white-tailed deer. Although closely related to bluetongue virus that can cause disease in sheep and cattle, North American EHDV historically has not been associated with disease in cattle or sheep. Severe disease in cattle has been reported with other EHDV strains from East Asia and the Middle East. To understand the potential role of viral genetics in the epidemiology of epizootic hemorrhagic disease, a molecular characterization of North American EHDV strains from 1955 to 2012 was conducted via conventional phylogenetic analysis and a new classification approach using motif fingerprint patterns. Overall, this study indicates that the genetic make-up of EHDV populations in North America have slowly evolved over time. The data also suggested limited reassortment events between serotypes 1 and 2 and introduces a new analysis tool for more detailed sequence pattern analysis. PMID:27107856

  19. Vaccines for Prevention of Bluetongue and Epizootic Hemorrhagic Disease in Livestock: A North American Perspective.

    PubMed

    McVey, D Scott; MacLachlan, N James

    2015-06-01

    Bluetongue (BT) and epizootic hemorrhagic disease (EHD) are noncontagious, insect-transmitted diseases of domestic and wild ruminants caused by related but distinct viruses. There are significant gaps in our scientific knowledge and available countermeasures to control an outbreak of orbivirus-induced disease, whether BT or EHD. Both BT virus (BTV) and EHD virus (EHDV) cause hemorrhagic fevers in susceptible ruminants; however, BT is principally a disease of domestic livestock whereas EHD is principally a disease of certain species of wild, non-African ungulates, notably white-tailed deer. The live-attenuated (modified live virus [MLV]) vaccines available in the United States for use in small ruminant livestock do provide good protection against clinical disease following infection with the homologous virus serotype. Although there is increasing justification that the use of MLV vaccines should be avoided if possible, these are the only vaccines currently available in the United States. Specifically, MLVs are used in California to protect sheep against infection with BTV serotypes 10, 11, and 17, and a MLV to BTV serotype 10 is licensed for use in sheep throughout the United States. These MLV vaccines may need to continue to be used in the immediate future for protective immunization of sheep and goats against BT. There are currently no licensed vaccines available for EHD in the United States other than autogenous vaccines. If there is a need to rapidly develop a vaccine to meet an emerging crisis associated with either BTV or EHDV infections, development of an inactivated virus vaccine in a conventional adjuvanted formulation will likely be required. With two doses of vaccine (and in some instances just one dose), inactivated vaccines can provide substantial immunity to the epizootic serotype of either BTV or EHDV. This strategy is similar to that used in the 2006-2008 BTV serotype 8 outbreaks in northern Europe that provided vaccine to the field within 2 years of

  20. Low-dose immunization with adenovirus expressing the thyroid-stimulating hormone receptor A-subunit deviates the antibody response toward that of autoantibodies in human Graves' disease.

    PubMed

    Chen, Chun-Rong; Pichurin, Pavel; Chazenbalk, Gregorio D; Aliesky, Holly; Nagayama, Yuji; McLachlan, Sandra M; Rapoport, Basil

    2004-01-01

    Immunization with adenovirus expressing the TSH receptor (TSHR) induces hyperthyroidism in 25-50% of mice. Even more effective is immunization with a TSHR A-subunit adenovirus (65-84% hyperthyroidism). Nevertheless, TSHR antibody characteristics in these mice do not mimic accurately those of autoantibodies in typical Graves' patients, with a marked TSH-blocking antibody response. We hypothesized that this suboptimal antibody response was consequent to the standard dose of TSHR-adenovirus providing too great an immune stimulus. To test this hypothesis, we compared BALB/c mice immunized with the usual number (10(11)) and with far fewer viral particles (10(9) and 10(7)). Regardless of viral dose, hyperthyroidism developed in a similar proportion (68-80%) of mice. We then examined the qualitative nature of TSHR antibodies in each group. Sera from all mice had TSH binding-inhibitory (TBI) activity after the second immunization, with TBI values in proportion to the viral dose. After the third injection, all groups had near-maximal TBI values. Remarkably, in confirmation of our hypothesis, immunization with progressively lower viral doses generated TSHR antibodies approaching the characteristics of autoantibodies in human Graves' disease as follows: 1) lower TSHR antibody titers on ELISA and 2) lower TSH-blocking antibody activity without decrease in thyroid-stimulating antibody activity. In summary, low-dose immunization with adenovirus expressing the free TSHR A-subunit provides an induced animal model with a high prevalence of hyperthyroidism as well as TSHR antibodies more closely resembling autoantibodies in Graves' disease. PMID:14576177

  1. Efficacy of helper-dependent adenovirus vector-mediated gene therapy in murine glycogen storage disease type Ia.

    PubMed

    Koeberl, Dwight D; Sun, B; Bird, A; Chen, Y T; Oka, K; Chan, L

    2007-07-01

    Genetic deficiency of glucose-6-phosphatase (G6Pase) underlies glycogen storage disease type Ia (GSD-Ia, also known as von Gierke disease; MIM 232200), an autosomal recessive disorder of metabolism associated with life-threatening hypoglycemia and growth retardation. We tested whether helper-dependent adenovirus (HDAd)-mediated hepatic delivery of G6Pase would lead to prolonged survival and sustained correction of the metabolic abnormalities in G6Pase knockout (KO) mice, a model for a severe form of GSD-Ia. An HDAd vector encoding G6Pase was administered intravenously (2 or 5 x 10(12)vector particles/kg) to 2-week-old (w.o.) G6Pase-KO mice. Following HDAd vector administration survival was prolonged to a median of 7 months, in contrast to untreated affected mice that did not survive past 3 weeks of age. G6Pase levels increased more than tenfold between 3 days and 28 weeks after HDAd injection (P < 0.03). The weights of untreated 2 w.o. G6Pase-KO mice were approximately half those of their unaffected littermates, and treatment stimulated their growth to the size of wild-type mice. Severe hypoglycemia and hypercholesterolemia, which are hallmarks of GSD-Ia both in humans and in mice, were also restored to normalcy by the treatment. Glycogen accumulation in the liver was markedly reduced. The efficacy of HDAd-G6Pase treatment in reversing the physiological and biochemical abnormalities associated with GSD-Ia in affected G6Pase-KO mice justifies further preclinical evaluation in murine and canine models of GSD-Ia. PMID:17505475

  2. A Recombinant Adenovirus Expressing P12A and 3C Protein of the Type O Foot-and-Mouth Disease Virus Stimulates Systemic and Mucosal Immune Responses in Mice

    PubMed Central

    Gao, Peng

    2016-01-01

    Foot-and-mouth disease (FMD) is a highly contagious livestock disease of cloven-hoofed animals which causes severe economic losses. The replication-deficient, human adenovirus-vectored FMD vaccine has been proven effective against FMD. However, the role of T-cell-mediated antiviral responses and the mucosae-mediated antiviral responses induced by the adenovirus-vectored FMD vaccine was rarely examined. Here, the capsid protein precursor P1-2A and viral protease 3C of the type O FMDV were expressed in replicative-deficient human adenovirus type 5 vector. BALB/c mice immunized intramuscularly and intraperitoneally with recombinant adenovirus rAdv-P12A3C elicited higher FMDV-specific IgG antibodies, IFN-γ, and IL-4 cytokines than those in mice immunized with inactivated FMDV vaccine. Moreover, BALB/c mice immunized with recombinant adenovirus rAdv-P12A3C by oral and intraocular-nasal immunization induced high FMDV-specific IgA antibodies. These results show that the recombinant adenovirus rAdv-P12A3C could resist FMDV comprehensively. This study highlights the potential of rAdv-P12A3C to serve as a type O FMDV vaccine. PMID:27478836

  3. A Recombinant Adenovirus Expressing P12A and 3C Protein of the Type O Foot-and-Mouth Disease Virus Stimulates Systemic and Mucosal Immune Responses in Mice.

    PubMed

    Xie, Yinli; Gao, Peng; Li, Zhiyong

    2016-01-01

    Foot-and-mouth disease (FMD) is a highly contagious livestock disease of cloven-hoofed animals which causes severe economic losses. The replication-deficient, human adenovirus-vectored FMD vaccine has been proven effective against FMD. However, the role of T-cell-mediated antiviral responses and the mucosae-mediated antiviral responses induced by the adenovirus-vectored FMD vaccine was rarely examined. Here, the capsid protein precursor P1-2A and viral protease 3C of the type O FMDV were expressed in replicative-deficient human adenovirus type 5 vector. BALB/c mice immunized intramuscularly and intraperitoneally with recombinant adenovirus rAdv-P12A3C elicited higher FMDV-specific IgG antibodies, IFN-γ, and IL-4 cytokines than those in mice immunized with inactivated FMDV vaccine. Moreover, BALB/c mice immunized with recombinant adenovirus rAdv-P12A3C by oral and intraocular-nasal immunization induced high FMDV-specific IgA antibodies. These results show that the recombinant adenovirus rAdv-P12A3C could resist FMDV comprehensively. This study highlights the potential of rAdv-P12A3C to serve as a type O FMDV vaccine. PMID:27478836

  4. Coccidian and nematode infections influence prevalence of antibody to myxoma and rabbit hemorrhagic disease viruses in European rabbits.

    PubMed

    Bertó-Moran, Alejandro; Pacios, Isabel; Serrano, Emmanuel; Moreno, Sacramento; Rouco, Carlos

    2013-01-01

    The interaction among several parasites in European rabbits (Oryctolagus cuniculus) is crucial to host fitness and to the epidemiology of myxomatosis and rabbit hemorrhagic disease. These diseases have caused significant reductions in rabbit populations on the Iberian Peninsula. Most studies have focused on the epidemiology and pathogenesis of these viruses individually, and little is known about interactions between these viruses and other parasites. Taking advantage of an experimental restocking program in Spain, the effects of coccidian and nematode infections on the probability of having detectable antibody to myxoma and rabbit hemorrhagic disease viruses were tested in European wild rabbits. For 14 mo, we monitored rabbit abundance and parasite loads (coccidia and nematodes) in three reintroduced rabbit populations. While coccidian and nematode loads explained seasonal antibody prevalences to myxoma virus, the pattern was less clear for rabbit hemorrhagic disease. Contrary to expectations, prevalence of antibody to myxoma virus was inversely proportional to coccidian load, while nematode load seemed to play a minor role. These results have implications for viral disease epidemiology and for disease management intended to increase rabbit populations in areas where they are important for ecosystem conservation. PMID:23307367

  5. Hemorrhagic disease in dogs infected with an unclassified intraendothelial piroplasm in southern Brazil.

    PubMed

    Loretti, Alexandre Paulino; Barros, Severo Sales

    2005-12-10

    A hemorrhagic disease affecting dogs in Brazil, referred to popularly as "nambiuvú" (bloody ears) and believed to be transmitted by ticks, has been observed in animals infected with an organism described originally in 1910 as a piroplasm, and known locally as Rangelia vitalii. In this series of 10 cases, the disease was characterized by anaemia, jaundice, fever, spleno- and lymphadenomegaly, hemorrhage in the gastrointestinal tract, and persistent bleeding from the nose, oral cavity and tips, margins and outer surface of the pinnae. The ixodid ticks Rhipicephalus sanguineus and Amblyomma aureolatum infested affected dogs from suburban and rural areas, respectively. Laboratory findings included regenerative anaemia, spherocytosis, icteric plasma and bilirubinuria. Those intracellular organisms were found in bone marrow smears but not in blood smears. Microscopically, zoites were seen within the cytoplasm of blood capillary endothelial cells. Parasitized and non-parasitized endothelial cells were positive immunohistochemically for von Willebrand factor (vWF). Langhans-type multinucleate giant cells were observed in the lymph nodes and choroid plexus. There was prominent erythrophagocytosis by macrophages in the lymph node sinuses and infiltration of the medullary cords by numerous plasma cells. Ultrastructurally, this organism had an apical complex that included a polar ring and rhoptries but no conoid. This parasite was contained within a parasitophorous vacuole that had a trilaminar membrane with villar protrusions and was situated in the cytoplasm of capillary endothelial cells. This organism tested positive by immunohistochemistry for Babesia microti. This pathogen was also positive by in situ hybridization for B. microti. Tentative clinical diagnosis in these cases was based on the history, clinical picture, haemogram and favorable response to therapy, and confirmed through microscopic examination of smears from the bone marrow or histological sections of

  6. Deaths from cerebrovascular diseases correlated to month of birth: elevated risk of death from subarachnoid hemorrhage among summer-born

    NASA Astrophysics Data System (ADS)

    Nonaka, K.; Imaizumi, Y.

    It has been suggested that maternal nutrition, and fetal and infant growth have an important effect on the risk of cardiovascular disease in adult life. We investigated the population-based distribution of deaths from cerebrovascular diseases (ICD9 codes 430, 431, or 434) in Japan in 1986-1994 as a function of birth month, by examining death-certificate records. For a total of 853 981 people born in the years 1900-1959, the distribution of the number of deaths according to the month of birth was compared with the distribution expected from the monthly numbers of all births for each sex and for the corresponding birth decade. For those born between 1920 and 1949, there were significant discrepancies between the actual numbers of deaths from subarachnoid hemorrhage (ICD9 430) and the numbers expected, and these differences were related to the month of birth. Those born in summer, June-September, consistently had an elevated risk of death, particularly men, where the excess risk was 8%-23%. This tendency was also observed, less distinctly but significantly, for deaths from intracerebral hemorrhage (ICD9 431), but was not observed for those dying from occlusion of the cerebral arteries (ICD9 434). The observation that the risk of dying from subarachnoid hemorrhage was more than 10% higher among those born in the summer implies that at least one in ten deaths from subarachnoid hemorrhage has its origin at a perinatal stage. Although variations in hypertension in later life, which could possibly be ''programmed'' during the intra-uterine stages, could be an explanation for this observation, the disease-specific nature of the observation suggests the involvement of aneurysm formation, which is a predominant cause of subarachnoid hemorrhage.

  7. Review of the 2012 Epizootic Hemorrhagic Disease Outbreak in Domestic Ruminants in the United States.

    PubMed

    Stevens, G; McCluskey, B; King, A; O'Hearn, E; Mayr, G

    2015-01-01

    An unusually large number of cases of Epizootic hemorrhagic disease (EHD) were observed in United States cattle and white-tailed deer in the summer and fall of 2012. USDA APHIS Veterinary Services area offices were asked to report on foreign animal disease investigations and state diagnostic laboratory submissions which resulted in a diagnosis of EHD based on positive PCR results. EHD was reported in the following species: cattle (129 herds), captive white-tailed deer (65 herds), bison (8 herds), yak (6 herds), elk (1 herd), and sheep (1 flock). A majority of the cases in cattle and bison were found in Nebraska, South Dakota, and Iowa. The majority of cases in captive white-tailed deer were found in Ohio, Iowa, Michigan, and Missouri. The most common clinical sign observed in the cattle and bison herds was oral lesions. The major observation in captive white-tailed deer herds was death. Average within-herd morbidity was 7% in cattle and bison herds, and 46% in captive white-tailed deer herds. The average within-herd mortality in captive white-tailed deer herds was 42%. PMID:26244773

  8. Review of the 2012 Epizootic Hemorrhagic Disease Outbreak in Domestic Ruminants in the United States

    PubMed Central

    Stevens, G.; McCluskey, B.; King, A.; O’Hearn, E.; Mayr, G.

    2015-01-01

    An unusually large number of cases of Epizootic hemorrhagic disease (EHD) were observed in United States cattle and white-tailed deer in the summer and fall of 2012. USDA APHIS Veterinary Services area offices were asked to report on foreign animal disease investigations and state diagnostic laboratory submissions which resulted in a diagnosis of EHD based on positive PCR results. EHD was reported in the following species: cattle (129 herds), captive white-tailed deer (65 herds), bison (8 herds), yak (6 herds), elk (1 herd), and sheep (1 flock). A majority of the cases in cattle and bison were found in Nebraska, South Dakota, and Iowa. The majority of cases in captive white-tailed deer were found in Ohio, Iowa, Michigan, and Missouri. The most common clinical sign observed in the cattle and bison herds was oral lesions. The major observation in captive white-tailed deer herds was death. Average within-herd morbidity was 7% in cattle and bison herds, and 46% in captive white-tailed deer herds. The average within-herd mortality in captive white-tailed deer herds was 42%. PMID:26244773

  9. Human Hemorrhagic Fever Causing Arenaviruses: Molecular Mechanisms Contributing to Virus Virulence and Disease Pathogenesis

    PubMed Central

    Shao, Junjie; Liang, Yuying; Ly, Hinh

    2015-01-01

    Arenaviruses include multiple human pathogens ranging from the low-risk lymphocytic choriomeningitis virus (LCMV) to highly virulent hemorrhagic fever (HF) causing viruses such as Lassa (LASV), Junin (JUNV), Machupo (MACV), Lujo (LUJV), Sabia (SABV), Guanarito (GTOV), and Chapare (CHPV), for which there are limited preventative and therapeutic measures. Why some arenaviruses can cause virulent human infections while others cannot, even though they are isolated from the same rodent hosts, is an enigma. Recent studies have revealed several potential pathogenic mechanisms of arenaviruses, including factors that increase viral replication capacity and suppress host innate immunity, which leads to high viremia and generalized immune suppression as the hallmarks of severe and lethal arenaviral HF diseases. This review summarizes current knowledge of the roles of each of the four viral proteins and some known cellular factors in the pathogenesis of arenaviral HF as well as of some human primary cell-culture and animal models that lend themselves to studying arenavirus-induced HF disease pathogenesis. Knowledge gained from these studies can be applied towards the development of novel therapeutics and vaccines against these deadly human pathogens. PMID:26011826

  10. Rabbit Hemorrhagic Disease Virus Variant Recombinant VP60 Protein Induces Protective Immunogenicity.

    PubMed

    Yang, Dong-Kun; Kim, Ha-Hyun; Nah, Jin-Ju; Song, Jae-Young

    2015-11-01

    Rabbit hemorrhagic disease virus (RHDV) is highly contagious and often causes fatal disease that affects both wild and domestic rabbits of the species Oryctolagus cuniculus. A highly pathogenic RHDV variant (RHDVa) has been circulation in the Korean rabbit population since 2007 and has a devastating effect on the rabbit industry in Korea. A highly pathogenic RHDVa was isolated from naturally infected rabbits, and the gene encoding the VP60 protein was cloned into a baculovirus transfer vector and expressed in insect cells. The hemagglutination titer of the Sf-9 cell lysate infected with recombinant VP60 baculovirus was 131,072 units/50 μl and of the supernatant 4,096 units/50 μl. Guinea pigs immunized twice intramuscularly with a trial inactivated RHDVa vaccine containing recombinant VP60 contained 2,152 hemagglutination inhibition (HI) geometric mean titers. The 8-week-old white rabbits inoculated with one vaccine dose were challenged with a lethal RHDVa 21 days later and showed 100% survival rates. The recombinant VP60 protein expressed in a baculovirus system induced high HI titers in guinea pigs and rendered complete protection, which led to the development of a novel inactivated RHDVa vaccine. PMID:26198122

  11. Genetic characterization of epizootic hemorrhagic disease virus strains isolated from cattle in Israel.

    PubMed

    Wilson, William C; Ruder, Mark G; Klement, Eyal; Jasperson, Dane C; Yadin, Hagai; Stallknecht, David E; Mead, Daniel G; Howerth, Elizabeth

    2015-06-01

    Epizootic hemorrhagic disease virus (EHDV), a member of the genus Orbivirus not reported previously in Israel, was isolated from Israeli cattle during a 'bluetongue-like' disease outbreak in 2006. To ascertain the origin of this new virus, three isolates from the outbreak were fully sequenced and compared with available sequences. Whilst the L2 gene segment clustered with the Australian EHDV serotype 7 (EHDV-7) reference strain, most of the other segments were clustered with EHDV isolates of African/Middle East origin, specifically Bahrain, Nigeria and South Africa. The M6 gene had genetic relatedness to the Australian/Asian strains, but with the limited data available the significance of this relationship is unclear. Only one EHDV-7 L2 sequence was available, and as this gene encodes the serotype-specific epitope, the relationship of these EHDV-7 L2 genes to an Australian EHDV-7 reflects the serotype association, not necessarily the origin. The genetic data indicated that the strains affecting Israel in 2006 may have been related to similar outbreaks that occurred in North Africa in the same year. This finding also supports the hypothesis that EHDV entered Israel during 2006 and was not present there before this outbreak. PMID:25701817

  12. Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle

    PubMed Central

    Medina, Gisselle N.; Montiel, Nestor; Diaz-San Segundo, Fayna; Sturza, Diego; Ramirez-Medina, Elizabeth; Grubman, Marvin J.

    2015-01-01

    Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4+ and CD8+ gamma interferon (IFN-γ)+ cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle. PMID:26607309

  13. Evaluation of a Fiber-Modified Adenovirus Vector Vaccine against Foot-and-Mouth Disease in Cattle.

    PubMed

    Medina, Gisselle N; Montiel, Nestor; Diaz-San Segundo, Fayna; Sturza, Diego; Ramirez-Medina, Elizabeth; Grubman, Marvin J; de los Santos, Teresa

    2016-02-01

    Novel vaccination approaches against foot-and-mouth disease (FMD) include the use of replication-defective human adenovirus type 5 (Ad5) vectors that contain the capsid-encoding regions of FMD virus (FMDV). Ad5 containing serotype A24 capsid sequences (Ad5.A24) has proved to be effective as a vaccine against FMD in livestock species. However, Ad5-vectored FMDV serotype O1 Campos vaccine (Ad5.O1C.2B) provides only partial protection of cattle against homologous challenge. It has been reported that a fiber-modified Ad5 vector expressing Arg-Gly-Asp (RGD) enhances transduction of antigen-presenting cells (APC) in mice. In the current study, we assessed the efficacy of a fiber-modified Ad5 (Adt.O1C.2B.RGD) in cattle. Expression of FMDV capsid proteins was superior in cultured cells infected with the RGD-modified vector. Furthermore, transgene expression of Adt.O1C.2B.RGD was enhanced in cell lines that constitutively express integrin αvβ6, a known receptor for FMDV. In contrast, capsid expression in cattle-derived enriched APC populations was not enhanced by infection with this vector. Our data showed that vaccination with the two vectors yielded similar levels of protection against FMD in cattle. Although none of the vaccinated animals had detectable viremia, FMDV RNA was detected in serum samples from animals with clinical signs. Interestingly, CD4(+) and CD8(+) gamma interferon (IFN-γ)(+) cell responses were detected at significantly higher levels in animals vaccinated with Adt.O1C.2B.RGD than in animals vaccinated with Ad5.O1C.2B. Our results suggest that inclusion of an RGD motif in the fiber of Ad5-vectored FMD vaccine improves transgene delivery and cell-mediated immunity but does not significantly enhance vaccine performance in cattle. PMID:26607309

  14. Comparative Phylodynamics of Rabbit Hemorrhagic Disease Virus in Australia and New Zealand

    PubMed Central

    Eden, John-Sebastian; Kovaliski, John; Duckworth, Janine A.; Swain, Grace; Mahar, Jackie E.; Strive, Tanja

    2015-01-01

    ABSTRACT The introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand during the 1990s as a means of controlling feral rabbits is an important case study in viral emergence. Both epidemics are exceptional in that the founder viruses share an origin and the timing of their release is known, providing a unique opportunity to compare the evolution of a single virus in distinct naive populations. We examined the evolution and spread of RHDV in Australia and New Zealand through a genome-wide evolutionary analysis, including data from 28 newly sequenced RHDV field isolates. Following the release of the Australian inoculum strain into New Zealand, no subsequent mixing of the populations occurred, with viruses from both countries forming distinct groups. Strikingly, the rate of evolution in the capsid gene was higher in the Australian viruses than in those from New Zealand, most likely due to the presence of transient deleterious mutations in the former. However, estimates of both substitution rates and population dynamics were strongly sample dependent, such that small changes in sample composition had an important impact on evolutionary parameters. Phylogeographic analysis revealed a clear spatial structure in the Australian RHDV strains, with a major division between those viruses from western and eastern states. Importantly, RHDV sequences from the state where the virus was first released, South Australia, had the greatest diversity and were diffuse throughout both geographic lineages, such that this region was likely a source population for the subsequent spread of the virus across the country. IMPORTANCE Most studies of viral emergence lack detailed knowledge about which strains were founders for the outbreak or when these events occurred. Hence, the human-mediated introduction of rabbit hemorrhagic disease virus (RHDV) into Australia and New Zealand from known starting stocks provides a unique opportunity to understand viral evolution

  15. Viral Hemorrhagic Fevers

    MedlinePlus

    ... Fever with Renal Syndrome Hendra Virus Disease Kyasanur Forest Disease Lassa Fever Lymphocytic Choriomeningitis (LCM) Marburg Hemorrhagic ... the rodent species carrying several of the New World arenaviruses, live in geographically restricted areas. Therefore, the ...

  16. Phylogenetic and pathogenic characterization of novel adenoviruses isolated from long-tailed ducks (Clangula hyemalis).

    PubMed

    Counihan, Katrina L; Skerratt, Lee F; Franson, J Christian; Hollmén, Tuula E

    2015-11-01

    Novel adenoviruses were isolated from a long-tailed duck (Clangula hyemalis) mortality event near Prudhoe Bay, Alaska in 2000. The long-tailed duck adenovirus genome was approximately 27 kb. A 907 bp hexon gene segment was used to design primers specific for the long-tailed duck adenovirus. Nineteen isolates were phylogenetically characterized based on portions of their hexon gene and 12 were most closely related to Goose adenovirus A. The remaining 7 shared no hexon sequences with any known adenoviruses. Experimental infections of mallards with a long-tailed duck reference adenovirus caused mild lymphoid infiltration of the intestine and paint brush hemorrhages of the mucosa and dilation of the intestine. This study shows novel adenoviruses from long-tailed ducks are diverse and provides further evidence that they should be considered in cases of morbidity and mortality in sea ducks. Conserved and specific primers have been developed that will help screen sea ducks for adenoviral infections. PMID:26342465

  17. Epistaxis in end stage liver disease masquerading as severe upper gastrointestinal hemorrhage

    PubMed Central

    Camus, Marine; Jensen, Dennis M; Matthews, Jason D; Ohning, Gordon V; Kovacs, Thomas O; Jutabha, Rome; Ghassemi, Kevin A; Machicado, Gustavo A; Dulai, Gareth S

    2014-01-01

    AIM: To describe the prevalence, diagnosis, treatment, and outcomes of end stage liver disease (ESLD) patients with severe epistaxis thought to be severe upper gastrointestinal hemorrhage (UGIH). METHODS: This observational single center study included all consecutive patients with ESLD and epistaxis identified from consecutive subjects hospitalized with suspected UGIH and prospectively enrolled in our databases of severe UGIH between 1998 and 2011. RESULTS: A total of 1249 patients were registered for severe UGIH in the data basis, 461 (36.9%) were cirrhotics. Epistaxis rather than UGIH was the bleeding source in 20 patients. All patients had severe coagulopathy. Epistaxis was initially controlled in all cases. Fifteen (75%) subjects required posterior nasal packing and 2 (10%) embolization in addition to correction of coagulopathy. Five (25%) patients died in the hospital, 12 (60%) received orthotopic liver transplantation (OLT), and 3 (15%) were discharged without OLT. The mortality rate was 63% in patients without OLT. CONCLUSION: Severe epistaxis in patients with ESLD is (1) a diagnosis of exclusion that requires upper endoscopy to exclude severe UGIH; and (2) associated with a high mortality rate in patients not receiving OLT. PMID:25320538

  18. European brown hare syndrome virus: relationship to rabbit hemorrhagic disease virus and other caliciviruses.

    PubMed Central

    Wirblich, C; Meyers, G; Ohlinger, V F; Capucci, L; Eskens, U; Haas, B; Thiel, H J

    1994-01-01

    Monoclonal antibodies directed against the capsid protein of rabbit hemorrhagic disease virus (RHDV) were used to identify field cases of European brown hare syndrome (EBHS) and to distinguish between RHDV and the virus responsible for EBHS. Western blot (immunoblot) analysis of liver extract of an EBHS virus (EBHSV)-infected hare revealed a single major capsid protein species of approximately 60 kDa that shared epitopes with the capsid protein of RHDV. RNA isolated from the liver of an EBHSV-infected hare contained two viral RNA species of 7.5 and 2.2 kb that comigrated with the genomic and subgenomic RNAs of RHDV and were recognized by labeled RHDV cDNA in Northern (RNA) hybridizations. The nucleotide sequence of the 3' 2.8 kb of the EBHSV genome was determined from four overlapping cDNA clones. Sequence analysis revealed an open reading frame that contains part of the putative RNA polymerase gene and the complete capsid protein gene. This particular genome organization is shared by RHDV but not by other known caliciviruses. The deduced amino acid sequence of the capsid protein of EBHSV was compared with the capsid protein sequences of RDDV and other caliciviruses. The amino acid sequence comparisons revealed that EBHSV is closely related to RHDV and distantly related to other caliciviruses. On the basis of their genome organization, it is suggested that caliciviruses be divided into three groups. Images PMID:7518531

  19. Diagnostic Tools for Bluetongue and Epizootic Hemorrhagic Disease Viruses Applicable to North American Veterinary Diagnosticians.

    PubMed

    Wilson, William C; Daniels, Peter; Ostlund, Eileen N; Johnson, Donna E; Oberst, Richard D; Hairgrove, Thomas B; Mediger, Jessica; McIntosh, Michael T

    2015-06-01

    This review provides an overview of current and potential new diagnostic tests for bluetongue (BT) and epizootic hemorrhagic disease (EHD) viruses compiled from international participants of the Orbivirus Gap Analysis Workshop, Diagnostic Group. The emphasis of this review is on diagnostic tools available to North American veterinary diagnosticians. Standard diagnostic tests are readily available for BT/EHD viruses, and there are described tests that are published in the World Organization for Animal Health (OIE) Terrestrial Manual. There is however considerable variation in the diagnostic approach to these viruses. Serological assays are well established, and many laboratories are experienced in running these assays. Numerous nucleic acid amplification assays are also available for BT virus (BTV) and EHD virus (EHDV). Although there is considerable experience with BTV reverse-transcriptase PCR (RT-PCR), there are no standards or comparisons of the protocols used by various state and federal veterinary diagnostic laboratories. Methods for genotyping BTV and EHDV isolates are available and are valuable tools for monitoring and analyzing circulating viruses. These methods include RT-PCR panels or arrays, RT-PCR and sequencing of specific genome segments, or the use of next-generation sequencing. In addition to enabling virus characterization, use of advanced molecular detection methods, including DNA microarrays and next-generation sequencing, significantly enhance the ability to detect unique virus strains that may arise through genetic drift, recombination, or viral genome segment reassortment, as well as incursions of new virus strains from other geographical areas. PMID:26086557

  20. Resolving the Origin of Rabbit Hemorrhagic Disease Virus: Insights from an Investigation of the Viral Stocks Released in Australia

    PubMed Central

    Eden, John-Sebastian; Read, Andrew J.; Duckworth, Janine A.; Strive, Tanja

    2015-01-01

    To resolve the evolutionary history of rabbit hemorrhagic disease virus (RHDV), we performed a genomic analysis of the viral stocks imported and released as a biocontrol measure in Australia, as well as a global phylogenetic analysis. Importantly, conflicts were identified between the sequences determined here and those previously published that may have affected evolutionary rate estimates. By removing likely erroneous sequences, we show that RHDV emerged only shortly before its initial description in China. PMID:26378178

  1. Resolving the Origin of Rabbit Hemorrhagic Disease Virus: Insights from an Investigation of the Viral Stocks Released in Australia.

    PubMed

    Eden, John-Sebastian; Read, Andrew J; Duckworth, Janine A; Strive, Tanja; Holmes, Edward C

    2015-12-01

    To resolve the evolutionary history of rabbit hemorrhagic disease virus (RHDV), we performed a genomic analysis of the viral stocks imported and released as a biocontrol measure in Australia, as well as a global phylogenetic analysis. Importantly, conflicts were identified between the sequences determined here and those previously published that may have affected evolutionary rate estimates. By removing likely erroneous sequences, we show that RHDV emerged only shortly before its initial description in China. PMID:26378178

  2. Association Between Reduced Risk of Intracerebral Hemorrhage and Pelvic Inflammatory Disease

    PubMed Central

    Tseng, Chun-Hung; Muo, Chih-Hsin; Lin, Ming-Chia; Kao, Chia-Hung

    2016-01-01

    Abstract This study examines whether pelvic inflammatory disease (PID) facilitates the development of intracerebral hemorrhage (ICH). By using outpatient claims data from the National Health Insurance Research Database (NHIRD) of Taiwan, we included the data of 25,508 patients who were newly diagnosed with PID between 1999 and 2004, and also from the Taiwan NHIRD, we randomly selected 102,032 women without PID, who were frequency-matched by age and entry-year and with 4 times the number of the PID patients, as the control cohort. We measured ICH risks associated with PID and comorbidities, including hyperlipidemia, diabetes, hypertension, ischemic heart disease, and atrial fibrillation, by the end of 2011. In comparison with the controls, the ICH hazard was less in the PID group with an adjusted hazard ratio (aHR) of 0.67 (95% confidence interval [CI]:0.50–0.90), which was noted by calculation with the Cox proportional regression model. The ICH risk in the PID patients reduced progressively with the advance of age, with aHRs of 0.75 (95% CI:0.41–1.39) and 0.50 (95% CI:0.29–0.88), respectively, in the age <35-year and age ≥50-year groups. ICH risk lowered gradually with the progress of PID severity, from mild PID with an aHR of 0.72 (95% CI:0.53–0.98) to severe PID with that of 0.30 (95% CI:0.10–0.92). PID patients without any comorbidites had lower ICH risk (aHR = 0.63, 95% CI:0.42–0.94) than the controls without any comorbidites did. Our findings revealed that PID is associated with reduced ICH development, especially for older patients. PMID:26844517

  3. Confusing untypical intestinal Behcet’s disease: Skip ulcers with severe lower gastrointestinal hemorrhage

    PubMed Central

    Wang, Zhen-Kai; Shi, Hui; Wang, Shao-Dong; Liu, Jiong; Zhu, Wei-Ming; Yang, Miao-Fang; Liu, Chan; Lu, Heng; Wang, Fang-Yu

    2014-01-01

    Behcet’s disease (BD) is a rare and life-long disorder characterized by inflammation of blood vessels throughout the body. BD was originally described in 1937 as a syndrome involving oral and genital ulceration in addition to ocular inflammation. Intestinal BD refers to colonic ulcerative lesions documented by objective measures in patients with BD. Many studies have shown that over 40% of BD patients have gastrointestinal complaints. Symptoms include abdominal pain, diarrhea, nausea, anorexia and abdominal distension. Although gastrointestinal symptoms are common, the demonstration of gastrointestinal ulcers is rare. This so-called intestinal BD accounts for approximately 1% of cases. There is no specific test for BD, and the diagnosis is based on clinical criteria. The manifestations of intestinal BD are similar to those of other colitis conditions such as Crohn’s disease or intestinal tuberculosis, thus, it is challenging for gastroenterologists to accurately diagnose intestinal BD in patients with ileo-colonic ulcers. However, giant ulcers distributed in the esophagus and ileocecal junction with gastrointestinal hemorrhage are rare in intestinal BD. Here, we present a case of untypical intestinal BD. The patient had recurrent aphthous ulceration of the oral mucosa, and esophageal and ileo-colonic ulceration, but no typical extra-intestinal symptoms. During examination, the patient had massive acute lower gastrointestinal bleeding. The patient underwent ileostomy after an emergency right hemicolectomy and partial ileectomy, and was subsequently diagnosed with incomplete-type intestinal BD by pathology. The literature on the evaluation and management of this condition is reviewed. PMID:24527178

  4. Dieulafoy's lesion-like bleeding: an underrecognized cause of upper gastrointestinal hemorrhage in patients with advanced liver disease.

    PubMed

    Akhras, Jamil; Patel, Pragnesh; Tobi, Martin

    2007-03-01

    Dieulafoy's lesion is a gastrointestinal submucosal artery that ruptures into the lumen causing massive hemorrhage. Until recently, failure to diagnose and treat patients endoscopically may have necessitated blind gastrectomy. Because arteriolar spider nevi abound in patients with liver disease and bleeding from such lesions has been described in the upper gastrointestinal tract, we reviewed our experience to determine whether a diagnosis of advanced liver disease could facilitate recognition and treatment of this type of arterial bleeding. Endoscopy records from 1991 to 1996 for all cases of upper gastrointestinal bleeding at our institution were reviewed. Dieulafoy's lesion-like bleeding was defined as arterial-type bleeding with no evidence of mucosal ulceration or erosions. Advanced liver disease was defined as signs of portal hypertension and/or cirrhosis or infiltrative liver disease. Dieulafoy's lesion-like bleeding was the cause in 6 of 4569 cases (0.13%). Five patients with Dieulafoy's lesion-like gastrointestinal hemorrhage had advanced liver disease compared with 954 of 4569 of all patients endoscoped for gastrointestinal hemorrhage for the period evaluated (OR = 19.04; 95% CI 2.1-900.8; p < 0.002 by Fisher's exact test). Dieulafoy's lesion-like bleeding was treated successfully with epinephrine injection and endoscopic cauterization in 5 of 6 patients with 1 patient requiring surgery. No other clinical associations were evident. Dieulafoy's lesion-like bleeding occurs more commonly in patients with advanced liver disease and should be included as a potential cause for bleeding in advanced liver disease and aggressively sought. PMID:17237996

  5. Human adenovirus-vectored foot-and-mouth disease vaccines: establishment of a vaccine product profile through in vitro testing.

    PubMed

    Brake, D A; McIlhaney, M; Miller, T; Christianson, K; Keene, A; Lohnas, G; Purcell, C; Neilan, J; Schutta, C; Barrera, J; Burrage, T; Brough, D E; Butman, B T

    2012-01-01

    Next generation, foot-and-mouth disease (FMD) molecular vaccines based on replication deficient human adenovirus serotype 5 viral vectored delivery of FMD capsid genes (AdFMD) are being developed by the United States Dept. of Homeland Security and industry partners. The strategic goal of this program is to develop AdFMD licensed vaccines for the USA National Veterinary Stockpile for use, if needed, as emergency response tools during an FMD outbreak. This vaccine platform provides a unique opportunity to develop a set of in vitro analytical parameters to generate an AdFMD vaccine product profile to replace the current lot release test for traditional, inactivated FMD vaccines that requires FMDV challenge in livestock. The possibility of an indirect FMD vaccine potency test based on a serological alternative was initially investigated for a lead vaccine candidate, Adt.A24. Results show that serum virus neutralization (SVN) based serology testing for Adt.A24 vaccine lot release is not feasible, at least not in the context of vaccine potency assessment at one week post-vaccination. Thus, an in vitro infectious titer assay (tissue culture infectious dose 50, TCID50) which measures FMD infectious (protein expression) titer was established. Pre-validation results show acceptable assay variability and linearity and these data support further studies to validate the TCID50 assay as a potential potency release test. In addition, a quantitative physiochemical assay (HPLC) and three immunochemical assays (Fluorescent Focus-Forming Unit (FFU); tissue culture expression dose 50 (TCED50); Western blot) were developed for potential use as in vitro assays to monitor AdFMD vaccine lot-to-lot consistency and other potential applications. These results demonstrate the feasibility of using a traditional modified-live vaccine virus infectivity assay in combination with a set of physiochemical and immunochemical tests to build a vaccine product profile that will ensure the each Ad

  6. An adenovirus vectored mucosal adjuvant augments protection of mice immunized intranasally with an adenovirus-vectored foot-and-mouth disease virus subunit vaccine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease virus (FMDV) is a highly contagious pathogen that causes severe morbidity and economic losses to the livestock industry in many countries. The oral and respiratory mucosae are the main ports of entry of FMDV, so the stimulation of local immunity in these tissues may help preve...

  7. Immunogenicity of adenovirus-derived porcine parvovirus-like particles displaying B and T cell epitopes of foot-and-mouth disease.

    PubMed

    Pan, Qunxing; Wang, Hui; Ouyang, Wei; Wang, Xiaoli; Bi, Zhenwei; Xia, Xingxia; Wang, Yongshan; He, Kongwang

    2016-01-20

    Virus-like particles (VLPs) vaccines combine many of the advantages of whole-virus vaccines and recombinant subunit vaccines, integrating key features that underlay their immunogenicity, safety and protective potential. We have hypothesized here the effective insertion of the VP1 epitopes (three amino acid residues 21-40, 141-160 and 200-213 in VP1, designated VPe) of foot-and-mouth disease (FMDV) within the external loops of PPV VP2 could be carried out without altering assembly based on structural and antigenic data. To investigate the possibility, development of two recombinant adenovirus rAd-PPV:VP2-FMDV:VPe a or rAd-PPV:VP2-FMDV:VPe b were expressed in HEK-293 cells. Out of the two insertion strategies tested, one of them tolerated an insert of 57 amino acids in one of the four external loops without disrupting the VLPs assembly. Mice were inoculated with the two recombinant adenoviruses, and an immunogenicity study showed that the highest levels of FMDV-specific humoral responses and T cell proliferation could be induced by rAd-PPV:VP2-FMDV:VPe b expressing hybrid PPV:VLPs (FMDV) in the absence of an adjuvant. Then, the protective efficacy of inoculating swine with rAd-PPV:VP2-FMDV:VPe b was tested. All pigs inoculated with rAd-PPV:VP2-FMDV:VPe b were protected from viral challenge, meanwhile the neutralizing antibody titers were significantly higher than those in the group inoculated with swine FMD type O synthetic peptide vaccine. Our results clearly demonstrate the potential usefulness of adenovirus-derived PPV VLPs as a vaccine strategy in prevention of FMDV. PMID:26685093

  8. Acute Small Bowel Hemorrhage in Three Patients with End-Stage Renal Disease: Diagnosis and Management by Angiographic Intervention

    SciTech Connect

    Yoon, Woong; Kim, Jae Kyu; Kim, Heoung Kil; Han, Young Min; Kang, Heoung Keun

    2002-03-15

    Three patients who had undergone hemodialysis for end-stage renal disease, presented with acute small bowel hemorrhage,and were treated with superselective transcatheter arterial embolization via coaxial microcatheters. In all patients pre-procedure upper gastrointestinal (GI) endoscopy and colonoscopy had failed to demonstrate the source of the hemorrhage. Selective diagnostic angiography revealed frank extravasations of contrast from the small bowel arteries (one jejunal artery and two ileal arteries). After superselection of feeding arteries with a microcatheter, transcatheter embolization using Gelfoam and microcoils was performed in all three patients. Immediate hemostasis was achieved in all patients and the patients were discharged free from symptoms 3-5 days after embolization. No evidence of intestinal ischemia or infarction was noted, with the time from procedure to last follow-up ranging from 4 to 12 months. We conclude that superselective angiography is a valuable tool for diagnosing and treating acute small bowel hemorrhage inpatients with end-stage renal disease when endoscopic evaluation has failed.

  9. Crohns disease with central nervous system vasculitis causing subarachnoid hemorrhage due to aneurysm and cerebral ischemic stroke.

    PubMed

    Garge, Shaileshkumar S; Vyas, Pooja D; Modi, Pranav D; Ghatge, Sharad

    2014-10-01

    Cerebral vasculitis secondary to Crohn's disease (CD) seems to be a very rare phenomenon. We report a 39-year-old male who presented with headache, vomiting, and left-sided weakness in the known case of CD. Cross-sectional imaging (computed tomography and magnetic resonance imaging,) showed right gangliocapsular acute infarct with supraclinoid cistern subarachnoid hemorrhage (SAH). Cerebral digital substraction angiography (DSA) showed dilatation and narrowing of right distal internal carotid artery (ICA). Left ICA was chronically occluded. His inflammatory markers were significantly raised. Imaging features are suggestive of cerebral vasculitis. Arterial and venous infarcts due to thrombosis are known in CD. Our case presented with acute subarachnoid hemorrhage in supraclinoid cistern due to rupture of tiny aneurysm of perforator arteries causing SAH and infarction in right basal ganglia. Patient was treated conservatively with immunosuppression along with medical management of SAH. PMID:25506170

  10. [Hemorrhagic form of dengue fever observed at the Infectious Diseases Department CHU Yalgado Ouédraogo, Burkina Faso].

    PubMed

    Mamoudou, Savadogo; Boushab, Boushab Mohamed

    2016-01-01

    Dengue is a re-emerging arboviral disease in tropical countries. Haemorrhagic form may be associated with circulatory failure and produce hypovolemic shock, which is often fatal. We report a series of three cases of hemorrhagic dengue observed at the Infectious Diseases Department CHU Yalgado Ouédraogo, Ouagadougou, in order to describe its epidemiological, clinical, and evolutive characteristics. Our study included young females who had an onset age of between 35 years and 45 years, residing in the city of Ouagadougou. Despite multiple concentrated platelets transfusions and symptomatic treatment, we mourned a death. The development of antivirals and of new vaccines is a silver lining to prevent dengue lethality. PMID:27303584

  11. Vector competence of Culicoides sonorensis (Diptera: Ceratopogonidae) to epizootic hemorrhagic disease virus serotype 7

    PubMed Central

    2012-01-01

    Background Culicoides sonorensis (Diptera: Ceratopogonidae) is a vector of epizootic hemorrhagic disease virus (EHDV) serotypes 1 and 2 in North America, where these viruses are well-known pathogens of white-tailed deer (WTD) and other wild ruminants. Although historically rare, reports of clinical EHDV infection in cattle have increased in some parts of the world over the past decade. In 2006, an EHDV-7 epizootic in cattle resulted in economic loss for the Israeli dairy industry. White-tailed deer are susceptible to EHDV-7 infection and disease; however, this serotype is exotic to the US and the susceptibility of C. sonorensis to this cattle-virulent EHDV is not known. The objective of the study was to determine if C. sonorensis is susceptible to EHDV-7 infection and is a competent vector. Methods To evaluate the susceptibility of C. sonorensis, midges were fed on EHDV-7 infected WTD, held at 22 ± 1°C, and processed individually for virus isolation and titration on 4–16 days post feeding (dpf). Midges with a virus titer of ≥102.7 median tissue culture infective doses (TCID50)/midge were considered potentially competent. To determine if infected C. sonorensis were capable of transmitting EHDV-7 to a host, a susceptible WTD was then fed on by a group of 14–16 dpf midges. Results From 4–16 dpf, 45% (156/350) of midges that fed on WTD with high titer viremia (>107 TCID50/ml) were virus isolation-positive, and starting from 10–16 dpf, 32% (35/109) of these virus isolation-positive midges were potentially competent (≥102.7 TCID50/midge). Midges that fed on infected deer transmitted the virus to a susceptible WTD at 14–16 dpf. The WTD developed viremia and severe clinical disease. Conclusion This study demonstrates that C. sonorensis is susceptible to EHDV-7 infection and can transmit the virus to susceptible WTD, thus, C. sonorensis should be considered a potential vector of EHDV-7. Together with previous work, this study demonstrates that North America

  12. Host and Potential Vector Susceptibility to an Emerging Orbivirus in the United States: Epizootic Hemorrhagic Disease Virus Serotype 6.

    PubMed

    Ruder, M G; Stallknecht, D E; Allison, A B; Mead, D G; Carter, D L; Howerth, E W

    2016-05-01

    Epizootic hemorrhagic disease viruses (EHDVs) are orbiviruses transmitted byCulicoidesbiting midges to domestic and wild ruminants. EHDV-1 and EHDV-2 are endemic in the United States, where epizootic hemorrhagic disease is the most significant viral disease of white-tailed deer (WTD;Odocoileus virginianus) and reports of epizootic hemorrhagic disease in cattle are increasing. In 2006, a reassortant EHDV-6 was isolated from dead WTD in Indiana and has been detected each subsequent year over a wide geographic region. Since EHDV-6 is not a historically endemic serotype in the United States, it is important to understand infection outcome in potential hosts. Specifically, we aimed to evaluate the pathogenicity of the virus in 2 primary US ruminant hosts (WTD and cattle) and the susceptibility of a confirmed US vector (Culicoides sonorensis). Five WTD and 4 cattle were inoculated with >10(6)TCID50EHDV-6 by intradermal and subcutaneous injection. All 5 WTD exhibited moderate to severe disease, and 3 died. Viremia was first detected 3 to 5 days postinfection (dpi) with surviving animals seroconverting by 10 dpi. Two of 4 inoculated cattle had detectable viremia, 5 to 10 dpi and 7 to 24 dpi, respectively. No clinical, hematologic, or pathologic abnormalities were observed. Antibodies were detected by 10 dpi in 3 of 4 cows.C. sonorensiswere fed on WTD blood spiked with EHDV-6 and held for 4 to 14 days postfeeding at 25°C. From 4 to 14 days postfeeding, 19 of 171 midges were virus isolation positive and 6 of 171 had ≥10(2.7)TCID50EHDV-6. Although outcomes varied, these studies demonstrate the susceptibility of ruminant and vector hosts in the United States for this recently emerged EHDV serotype. PMID:26459518

  13. A Multiplex Real-time Reverse Transcription Polymerase Chain Reaction Assay for Detection and Differentiation of Bluetongue Virus and Epizootic Hemorrhagic Disease Virus Serogroups

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bluetongue virus (BTV) causes disease in domestic and wild ruminants resulting in significant economic loss. The closely related Epizootic hemorrhagic diseases virus (EHDV) has been associated with bluetongue-like disease in cattle. Although US EHDV strains have not been experimentally proven to cau...

  14. Transmission and Epidemiology of Bluetongue and Epizootic Hemorrhagic Disease in North America: Current Perspectives, Research Gaps, and Future Directions.

    PubMed

    Ruder, Mark G; Lysyk, Timothy J; Stallknecht, David E; Foil, Lane D; Johnson, Donna J; Chase, Christopher C; Dargatz, David A; Gibbs, E Paul J

    2015-06-01

    Bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) are arthropod-transmitted viruses in the genus Orbivirus of the family Reoviridae. These viruses infect a variety of domestic and wild ruminant hosts, although the susceptibility to clinical disease associated with BTV or EHDV infection varies greatly among host species, as well as between individuals of the same species. Since their initial detection in North America during the 1950s, these viruses have circulated in endemic and epidemic patterns, with occasional incursions to more northern latitudes. In recent years, changes in the pattern of BTV and EHDV infection and disease have forced the scientific community to revisit some fundamental areas related to the epidemiology of these diseases, specifically in relation to virus-vector-host interactions and environmental factors that have potentially enabled the observed changes. The aim of this review is to identify research and surveillance gaps that obscure our understanding of BT and EHD in North America. PMID:26086556

  15. Febrile ulceronecrotic Mucha-Habermann disease following suspected hemorrhagic chickenpox infection in a 20-month-old boy.

    PubMed

    Lode, H N; Döring, P; Lauenstein, P; Hoeger, P; Dombrowski, F; Bruns, R

    2015-10-01

    We present the youngest pediatric patient so far with febrile ulcerative Mucha-Haberman disease (FUMHD) after an admitting clinical picture of hemorrhagic varicella infection. With a time to diagnosis of 25 days, the 20-month-old boy responded to low dose cyclosporine and prednisolone given for 3 months and is free of disease after 4 years of follow up. We describe a polyclonal CD8+ T cell response with elevated pro-inflammatory cytokines and a fivefold upregulation of the high-affinity Fc receptor type I (CD64) on granulocytes. Early consideration of FUMHD in the differential diagnosis of a systemic inflammatory disease combined with a generalized necrotizing rash is important for early and adequate management of children with this rare and challenging disease. PMID:25627543

  16. Effect of Temperature on Replication of Epizootic Hemorrhagic Disease Viruses in Culicoides sonorensis (Diptera: Ceratopogonidae).

    PubMed

    Ruder, Mark G; Stallknecht, David E; Howerth, Elizabeth W; Carter, Deborah L; Pfannenstiel, Robert S; Allison, Andrew B; Mead, Daniel G

    2015-09-01

    Replication of arboviruses, including orbiviruses, within the vector has been shown to be temperature dependent. Cooler ambient temperatures slow virus replication in arthropod vectors, whereas viruses replicate faster and to higher titers at warmer ambient temperatures. Previous research with epizootic hemorrhagic disease virus (EHDV) serotype 1 demonstrated that higher temperatures were associated with shorter extrinsic incubation periods in Culicoides sonorensis Wirth & Jones, a confirmed vector of EHDV in North America. To further our understanding of the effect of temperature on replication of EHDV within the vector, C. sonorensis were experimentally infected with one of three EHDV strains representing three serotypes (1, 2, and 7). Midges were fed defibrinated white-tailed deer (Odocoileus virginianus) blood spiked with EHDV (≥10(6.5) TCID(50)/ml) through a parafilm membrane using an artificial feeding device and were then held at 20, 25, or 30°C. In addition to this in vitro method, a white-tailed deer experimentally infected with EHDV-7 was used to provide an infectious bloodmeal to determine if the results were comparable with those from the in vitro feeding method. Whole midges were processed for virus isolation and titration at regular intervals following feeding; midges with ≥10(2.7) TCID(50) were considered potentially competent to transmit virus. The virus recovery rates were high throughout the study and all three viruses replicated within C. sonorensis to high titer (≥ 10(2.7) TCID(50)/midge). Across all virus strains, the time to detection of potentially competent midges decreased with increasing temperature: 12-16 d postfeeding (dpf) at 20°C, 4-6 dpf at 25°C, and 2-4 dpf at 30°C. Significant differences in replication of the three viruses in C. sonorensis were observed, with EHDV-2 replicating to a high titer in a smaller proportion of midges and with lower peak titers. The findings are consistent with previous studies of related

  17. Hemorrhagic Stroke

    MedlinePlus

    A stroke is a medical emergency. There are two types - ischemic and hemorrhagic. Hemorrhagic stroke is the less common type. It happens when ... an artery wall that breaks open. Symptoms of stroke are Sudden numbness or weakness of the face, ...

  18. Adenovirus-mediated delivery into myocytes of muscle glycogen phosphorylase, the enzyme deficient in patients with glycogen-storage disease type V.

    PubMed Central

    Baqué, S; Newgard, C B; Gerard, R D; Guinovart, J J; Gómez-Foix, A M

    1994-01-01

    The feasibility of using adenovirus as a vector for the introduction of glycogen phosphorylase activity into myocytes has been examined. We used the C2C12 myoblast cell line to assay the impact of phosphorylase gene transfer on myocyte glycogen metabolism and to reproduce in vitro the two strategies proposed for the treatment of muscle genetic diseases, myoblast transplantation and direct DNA delivery. In this study, a recombinant adenovirus containing the muscle glycogen phosphorylase cDNA transcribed from the cytomegalovirus promoter (AdCMV-MGP) was used to transduce both differentiating myoblasts and nondividing mature myotube cells. Muscle glycogen phosphorylase mRNA levels and total phosphorylase activity were increased in both cell types after viral treatment although more efficiently in the differentiated myotubes. The increase in phosphorylase activity was transient (15 days) in myoblasts whereas in myotubes higher levels of phosphorylase gene expression and activity were reached, which remained above control levels for the duration of the study (20 days). The introduction of muscle phosphorylase into myotubes enhanced their glycogenolytic capacity. AdCMV MGP-transduced myotubes had lower glycogen levels under basal conditions. In addition, these engineered cells showed more extensive glycogenolysis in response to both adrenaline, which stimulates glycogen phosphorylase phosphorylation, and carbonyl cyanide m-chlorophenylhydrazone, a metabolic uncoupler. In conclusion, transfer of the muscle glycogen phosphorylase cDNA into myotubes confers an enhanced and regulatable glycogenolytic capacity. Thus this system might be useful for delivery of muscle glycogen phosphorylase and restoration of glycogenolysis in muscle cells from patients with muscle phosphorylase deficiency (McArdle's disease). Images Figure 1 Figure 2 Figure 5 PMID:7818463

  19. Genetic analysis of the NS1 and NS3 genes from the prototype serotype of Bluetongue and Epizootic Hemorrhagic Disease Viruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Bluetongue virus (BTV) and epizootic hemorrhagic disease virus (EHDV) are arthropod-borne viruses of significant animal agriculture importance. Clinical disease caused by BTV is most commonly observed in sheep and some wild ruminants; however, the recent outbreak in European Union has resulted in se...

  20. Viral Genome-Linked Protein (VPg) Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV)

    PubMed Central

    Zhu, Jie; Wang, Binbin; Miao, Qiuhong; Tan, Yonggui; Li, Chuanfeng; Chen, Zongyan; Guo, Huimin; Liu, Guangqing

    2015-01-01

    Rabbit hemorrhagic disease virus (RHDV), the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg) is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E) in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation. PMID:26599265

  1. Viral Genome-Linked Protein (VPg) Is Essential for Translation Initiation of Rabbit Hemorrhagic Disease Virus (RHDV).

    PubMed

    Zhu, Jie; Wang, Binbin; Miao, Qiuhong; Tan, Yonggui; Li, Chuanfeng; Chen, Zongyan; Guo, Huimin; Liu, Guangqing

    2015-01-01

    Rabbit hemorrhagic disease virus (RHDV), the causative agent of rabbit hemorrhagic disease, is an important member of the caliciviridae family. Currently, no suitable tissue culture system is available for proliferating RHDV, limiting the study of the pathogenesis of RHDV. In addition, the mechanisms underlying RHDV translation and replication are largely unknown compared with other caliciviridae viruses. The RHDV replicon recently constructed in our laboratory provides an appropriate model to study the pathogenesis of RHDV without in vitro RHDV propagation and culture. Using this RHDV replicon, we demonstrated that the viral genome-linked protein (VPg) is essential for RHDV translation in RK-13 cells for the first time. In addition, we showed that VPg interacts with eukaryotic initiation factor 4E (eIF4E) in vivo and in vitro and that eIF4E silencing inhibits RHDV translation, suggesting the interaction between VPg and eIF4E is involved in RHDV translation. Our results support the hypothesis that VPg serves as a novel cap substitute during the initiation of RHDV translation. PMID:26599265

  2. Dengue hemorrhagic fever

    MedlinePlus

    Hemorrhagic dengue; Dengue shock syndrome; Philippine hemorrhagic fever; Thai hemorrhagic fever; Singapore hemorrhagic fever ... Four different dengue viruses are known to cause dengue hemorrhagic fever. Dengue hemorrhagic fever occurs when a person is bitten by ...

  3. Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever

    PubMed Central

    Mendenhall, Michelle; Russell, Andrew; Smee, Donald F.; Hall, Jeffery O.; Skirpstunas, Ramona; Furuta, Yousuke; Gowen, Brian B.

    2011-01-01

    Background Lassa and Junín viruses are the most prominent members of the Arenaviridae family of viruses that cause viral hemorrhagic fever syndromes Lassa fever and Argentine hemorrhagic fever, respectively. At present, ribavirin is the only antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of disease and its toxicity, safer and more effective antivirals are needed. Methodology/Principal Findings Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichindé virus (PICV) to further preclinical development of T-705 (Favipiravir), a promising broad-spectrum inhibitor of RNA virus infections. The guinea pig-adapted passage 19 PICV was uniformly lethal with an LD50 of ∼5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300 mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV-induced disease even when therapy was initiated one week after virus challenge when animals were already significantly ill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductions in peak serum virus titers and AST concentrations in favipiravir-treated animals. Moreover, a sharp decrease in body temperature was observed shortly after the start of treatment. Oral ribavirin was also evaluated, and although effective, the slower rate of recovery may be a sign of the drug's known toxicity. Conclusions/Significance Our findings support further development of favipiravir for the treatment of severe arenaviral infections. The optimization of the experimental favipiravir treatment regimen in the PICV guinea pig model will inform critical future studies in the same species based

  4. Effects of Adenovirus-Mediated Delivery of the Human Hepatocyte Growth Factor Gene in Experimental Radiation-Induced Heart Disease

    SciTech Connect

    Hu Shunying; Chen Yundai; Li Libing; Chen Jinlong; Wu Bin; Zhou, Xiao; Zhi Guang; Li Qingfang; Wang Rongliang; Duan Haifeng; Guo Zikuan; Yang Yuefeng; Xiao Fengjun; Wang Hua; Wang Lisheng

    2009-12-01

    Purpose: Irradiation to the heart may lead to late cardiovascular complications. The purpose of this study was to investigate whether adenovirus-mediated delivery of the human hepatocyte growth factor gene could reduce post-irradiation damage of the rat heart and improve heart function. Methods and Materials: Twenty rats received single-dose irradiation of 20 Gy gamma ray locally to the heart and were randomized into two groups. Two weeks after irradiation, these two groups of rats received Ad-HGF or mock adenovirus vector intramyocardial injection, respectively. Another 10 rats served as sham-irradiated controls. At post-irradiation Day 120, myocardial perfusion was tested by myocardial contrast echocardiography with contrast agent injected intravenously. At post-irradiation Day 180, cardiac function was assessed using the Langendorff technique with an isolated working heart model, after which heart samples were collected for histological evaluation. Results: Myocardial blood flow was significantly improved in HGF-treated animals as measured by myocardial contrast echocardiography at post-irradiation Day 120 . At post-irradiation Day 180, cardiac function was significantly improved in the HGF group compared with mock vector group, as measured by left ventricular peak systolic pressure (58.80 +- 9.01 vs. 41.94 +- 6.65 mm Hg, p < 0.05), the maximum dP/dt (5634 +- 1303 vs. 1667 +- 304 mm Hg/s, p < 0.01), and the minimum dP/dt (3477 +- 1084 vs. 1566 +- 499 mm Hg/s, p < 0.05). Picrosirius red staining analysis also revealed a significant reduction of fibrosis in the HGF group. Conclusion: Based on the study findings, hepatocyte growth factor gene transfer can attenuate radiation-induced cardiac injury and can preserve cardiac function.

  5. Intrastriatal Transplantation of Adenovirus-Generated Induced Pluripotent Stem Cells for Treating Neuropathological and Functional Deficits in a Rodent Model of Huntington’s Disease

    PubMed Central

    Fink, Kyle D.; Crane, Andrew T.; Lévêque, Xavier; Dues, Dylan J.; Huffman, Lucas D.; Moore, Allison C.; Story, Darren T.; DeJonge, Rachel E.; Antcliff, Aaron; Starski, Phillip A.; Lu, Ming; Lescaudron, Laurent; Rossignol, Julien

    2014-01-01

    Induced pluripotent stem cells (iPSCs) show considerable promise for cell replacement therapies for Huntington’s disease (HD). Our laboratory has demonstrated that tail-tip fibroblasts, reprogrammed into iPSCs via two adenoviruses, can survive and differentiate into neuronal lineages following transplantation into healthy adult rats. However, the ability of these cells to survive, differentiate, and restore function in a damaged brain is unknown. To this end, adult rats received a regimen of 3-nitropropionic acid (3-NP) to induce behavioral and neuropathological deficits that resemble HD. At 7, 21, and 42 days after the initiation of 3-NP or vehicle, the rats received intrastriatal bilateral transplantation of iPSCs. All rats that received 3-NP and vehicle treatment displayed significant motor impairment, whereas those that received iPSC transplantation after 3-NP treatment had preserved motor function. Histological analysis of the brains of these rats revealed significant decreases in optical densitometric measures in the striatum, lateral ventricle enlargement, as well as an increase in striosome size in all rats receiving 3-NP when compared with sham rats. The 3-NP-treated rats given transplants of iPSCs in the 7- or 21-day groups did not exhibit these deficits. Transplantation of iPSCs at the late-stage (42-day) time point did not protect against the 3-NP-induced neuropathology, despite preserving motor function. Transplanted iPSCs were found to survive and differentiate into region-specific neurons in the striatum of 3-NP rats, at all transplantation time points. Taken together, these results suggest that transplantation of adenovirus-generated iPSCs may provide a potential avenue for therapeutic treatment of HD. PMID:24657963

  6. Vascular Diseases of the Spinal Cord: Infarction, Hemorrhage, and Venous Congestive Myelopathy.

    PubMed

    Vuong, Shawn M; Jeong, William J; Morales, Humberto; Abruzzo, Todd A

    2016-10-01

    Vascular pathologies of the spinal cord are rare and often overlooked. This article presents clinical and imaging approaches to the diagnosis and management of spinal vascular conditions most commonly encountered in clinical practice. Ischemia, infarction, hemorrhage, aneurysms, and vascular malformations of the spine and spinal cord are discussed. Pathophysiologic mechanisms, clinical classification schemes, clinical presentations, imaging findings, and treatment modalities are considered. Recent advances in genetic and syndromic vascular pathologies of the spinal cord are also discussed. Clinically relevant spinal vascular anatomy is reviewed in detail. PMID:27616317

  7. SPRi-based adenovirus detection using a surrogate antibody method.

    PubMed

    Abadian, Pegah N; Yildirim, Nimet; Gu, April Z; Goluch, Edgar D

    2015-12-15

    Adenovirus infection, which is a waterborne viral disease, is one of the most prevelant causes of human morbidity in the world. Thus, methods for rapid detection of this infectious virus in the environment are urgently needed for public health protection. In this study, we developed a rapid, real-time, sensitive, and label-free SPRi-based biosensor for rapid, sensitive and highly selective detection of adenoviruses. The sensing protocol consists of mixing the sample containing adenovirus with a predetermined concentration of adenovirus antibody. The mixture was filtered to remove the free antibodies from the sample. A secondary antibody, which was specific to the adenovirus antibody, was immobilized onto the SPRi chip surface covalently and the filtrate was flowed over the sensor surface. When the free adenovirus antibodies bound to the surface-immobilized secondary antibodies, we observed this binding via changes in reflectivity. In this approach, a higher amount of adenoviruses resulted in fewer free adenovirus antibodies and thus smaller reflectivity changes. A dose-response curve was generated, and the linear detection range was determined to be from 10 PFU/mL to 5000 PFU/mL with an R(2) value greater than 0.9. The results also showed that the developed biosensing system had a high specificity towards adenovirus (less than 20% signal change when tested in a sample matrix containing rotavirus and lentivirus). PMID:26232675

  8. Innate Immunity to Adenovirus

    PubMed Central

    Hendrickx, Rodinde; Stichling, Nicole; Koelen, Jorien; Kuryk, Lukasz; Lipiec, Agnieszka

    2014-01-01

    Abstract Human adenoviruses are the most widely used vectors in gene medicine, with applications ranging from oncolytic therapies to vaccinations, but adenovirus vectors are not without side effects. In addition, natural adenoviruses pose severe risks for immunocompromised people, yet infections are usually mild and self-limiting in immunocompetent individuals. Here we describe how adenoviruses are recognized by the host innate defense system during entry and replication in immune and nonimmune cells. Innate defense protects the host and represents a major barrier to using adenoviruses as therapeutic interventions in humans. Innate response against adenoviruses involves intrinsic factors present at constant levels, and innate factors mounted by the host cell upon viral challenge. These factors exert antiviral effects by directly binding to viruses or viral components, or shield the virus, for example, soluble factors, such as blood clotting components, the complement system, preexisting immunoglobulins, or defensins. In addition, Toll-like receptors and lectins in the plasma membrane and endosomes are intrinsic factors against adenoviruses. Important innate factors restricting adenovirus in the cytosol are tripartite motif-containing proteins, nucleotide-binding oligomerization domain-like inflammatory receptors, and DNA sensors triggering interferon, such as DEAD (Asp-Glu-Ala-Asp) box polypeptide 41 and cyclic guanosine monophosphate–adenosine monophosphate synthase. Adenovirus tunes the function of antiviral autophagy, and counters innate defense by virtue of its early proteins E1A, E1B, E3, and E4 and two virus-associated noncoding RNAs VA-I and VA-II. We conclude by discussing strategies to engineer adenovirus vectors with attenuated innate responses and enhanced delivery features. PMID:24512150

  9. Successful liver transplantation following veno-arterial extracorporeal membrane oxygenation in a child with fulminant Wilson disease and severe pulmonary hemorrhage: a case report.

    PubMed

    Son, Seung Kook; Oh, Seak Hee; Kim, Kyung Mo; Lee, Yeoun Joo; Jhang, Won Kyoung; Park, Seong Jong; Shin, Hong Ju; Park, Jeong-Jun; Kim, Tae Hoon; Kim, Dae Yeon; Hwang, Shin; Park, Kwang-Min; Lee, Young-Joo; Lee, Sung-Gyu

    2012-11-01

    Massive pulmonary hemorrhage and other serious cardiopulmonary diseases in patients with fulminant hepatitis result not only in graft failure but also mortality after LT. ECMO is used to treat children with cardiorespiratory failure refractory to conventional intensive care. We describe a five-yr-old girl with genetically confirmed fulminant Wilson disease and severe pulmonary hemorrhage who underwent successful primary LT following veno-arterial ECMO. To our knowledge, this is the first report of successful primary LT in a patient using veno-arterial ECMO. The present case demonstrates that ECMO, as a bridging modality to LT, may be necessary to manage both massive pulmonary hemorrhage and possible graft loss because of hypoxemia. PMID:22093921

  10. Innocuity of a commercial live attenuated vaccine for epizootic hemorrhagic disease virus serotype 2 in late-term pregnant cows.

    PubMed

    Spedicato, Massimo; Carmine, Irene; Teodori, Liana; Leone, Alessandra; Portanti, Ottavio; Marini, Valeria; Pisciella, Maura; Lorusso, Alessio; Savini, Giovanni

    2016-03-14

    Epizootic hemorrhagic disease (EHD) is an arthropod-borne infectious viral disease sustained by the epizootic hemorrhagic disease virus (EHDV). The only commercially available and currently used vaccines are manufactured for EHDV-2 in Japan, either live or inactivated vaccines. In this study we tested the innocuity for fetuses of the live attenuated EHDV-2 vaccine in five late-term pregnant cows. Whole blood and serum samples were collected from dams and screened for the presence of EHDV-2 RNA, infectious virus and antibodies. After calving, whole blood and serum samples collected from calves, before and after colostrum intake, were also tested for antibodies and for virus detection. In dams, neither fever nor clinical signs were observed. All of them seroconverted and a strong humoral response was detected throughout the sampling period. All blood samples tested negative for EHDV-2 except for one sample collected from a dam 11 days post-vaccination which tested positive at virus isolation at the third cell passage following two rounds of blind passages. Although they had free access to colostrum, calves tested serologically negative for EHDV-2 during the entire course of the experiment. Overall, the tested live attenuated vaccine can be safely administered to late-term pregnant cows as it was not demonstrated to cross the placental barrier. The safety of the live-attenuated vaccine is further confirmed by the emergence of Ibaraki virus in 2013 in Japan which is apparently not related to the spread of the vaccine strain currently used in Japan. PMID:26876438

  11. Increased levels of Porphyromonas gingivalis are associated with ischemic and hemorrhagic cerebrovascular disease in humans: an in vivo study

    PubMed Central

    GHIZONI, Janaina Salomon; TAVEIRA, Luís Antônio de Assis; GARLET, Gustavo Pompermaier; GHIZONI, Marcos Flávio; PEREIRA, Jefferson Ricardo; DIONÍSIO, Thiago José; BROZOSKI, Daniel Thomas; SANTOS, Carlos Ferreira; SANT'ANA, Adriana Campos Passanezi

    2012-01-01

    Objective: This study investigated the role of periodontal disease in the development of stroke or cerebral infarction in patients by evaluating the clinical periodontal conditions and the subgingival levels of periodontopathogens. Material and Methods: Twenty patients with ischemic (I-CVA) or hemorrhagic (H-CVA) cerebrovascular episodes (test group) and 60 systemically healthy patients (control group) were evaluated for: probing depth, clinical attachment level, bleeding on probing and plaque index. Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were both identified and quantified in subgingival plaque samples by conventional and real-time PCR, respectively. Results: The test group showed a significant increase in each of the following parameters: pocket depth, clinical attachment loss, bleeding on probing, plaque index and number of missing teeth when compared to control values (p<0.05, unpaired t-test). Likewise, the test group had increased numbers of sites that were contaminated with P. gingivalis (60%x10%; p<0.001; chi-squared test) and displayed greater prevalence of periodontal disease, with an odds ratio of 48.06 (95% CI: 5.96-387.72; p<0.001). Notably, a positive correlation between probing depth and the levels of P. gingivalis in ischemic stroke was found (r=0.60; p=0.03; Spearman's rank correlation coefficient test). A. actinomycetemcomitans DNA was not detected in any of the groups by conventional or real-time PCR. Conclusions: Stroke patients had deeper pockets, more severe attachment loss, increased bleeding on probing, increased plaque indexes, and in their pockets harbored increased levels of P. gingivalis. These findings suggest that periodontal disease is a risk factor for the development of cerebral hemorrhage or infarction. Early treatment of periodontitis may counteract the development of cerebrovascular episodes. PMID:22437687

  12. Development of a reverse genetics system for epizootic hemorrhagic disease virus and evaluation of novel strains containing duplicative gene rearrangements.

    PubMed

    Yang, Tao; Zhang, Jikai; Xu, Qingyuan; Sun, Encheng; Li, Junping; Lv, Shuang; Feng, Yufei; Zhang, Qin; Wang, Haixiu; Wang, Hua; Wu, Donglai

    2015-09-01

    Epizootic haemorrhagic disease is a non-contagious infectious viral disease of wild and domestic ruminants caused by epizootic hemorrhagic disease virus (EHDV). EHDV belongs to the genus Orbivirus within the family Reoviridae and is transmitted by insects of the genus Culicoides. The impact of epizootic haemorrhagic disease is underscored by its designation as a notifiable disease by the Office International des Epizooties. The EHDV genome consists of 10 linear dsRNA segments (Seg1-Seg10). Until now, no reverse genetics system (RGS) has been developed to generate replication-competent EHDV entirely from cloned cDNA, hampering detailed functional analyses of EHDV biology. Here, we report the generation of viable EHDV entirely from cloned cDNAs. A replication-competent EHDV-2 (Ibaraki BK13 strain) virus incorporating a marker mutation was rescued by transfection of BHK-21 cells with expression plasmids and in vitro synthesized RNA transcripts. Using this RGS, two additional modified EHDV-2 viruses were also generated: one that contained a duplex concatemeric Seg9 gene and another that contained a duplex concatemeric Seg10 gene. The modified EHDV-2 with a duplex Seg9 gene was genetically stable during serial passage in BHK-21 cells. In contrast, the modified EHDV-2 with a duplex Seg10 gene was unstable during serial passage, but displayed enhanced replication kinetics in vitro when compared with the WT virus. This RGS provides a new platform for the investigation of EHDV replication, pathogenesis and novel EHDV vaccines. PMID:25998915

  13. Peripheral infection with adenovirus causes unexpected long-term brain inflammation in animals injected intracranially with first-generation, but not with high-capacity, adenovirus vectors: Toward realistic long-term neurological gene therapy for chronic diseases

    PubMed Central

    Thomas, Clare E.; Schiedner, Gudrun; Kochanek, Stefan; Castro, Maria G.; Löwenstein, Pedro R.

    2000-01-01

    Although adenoviral vectors provide prolonged gene expression in the brain by comparison to peripheral organs, expression is eliminated by a severe inflammatory infiltration (i.e., activated macrophages/microglia and T-lymphocytes) after peripheral infection with adenovirus. Here, we demonstrate that high-capacity adenoviral (HC-Ad) vectors succeed in maintaining long-term transgene expression in the brain, even in the presence of an active peripheral immunization with adenovirus that completely eliminates expression from first-generation vectors within 60 days. Importantly, even 60 days after the peripheral infection, brains injected with first-generation vectors exhibited evidence of a chronic infiltration of CD8+ cells, macrophage/microglial activation, and up-regulation of brain MHC-I expression. No inflammation was observed in the brains injected with the HC-Ad vector. Thus, these results demonstrate that HC-Ad vectors will allow safe, stable, and long-term transgene expression in the brain, even in the presence of peripheral infection with adenovirus. This markedly improves the prospects for the use of adenoviral vectors for long-term gene therapy of neurological disorders. PMID:10840055

  14. Detection of a Novel Reassortant Epizootic Hemorrhagic Disease Virus in the United States Containing RNA Segments Derived from Both Exotic and Endemic Serotypes

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Epizootic hemorrhagic disease virus (EHDV) is a Culicoides-transmitted orbivirus that infects domestic and wild ruminants and is provisionally distributed throughout Africa, North America, Australia, East Asia, and the Middle East. Historically, of the seven proposed serotypes of EHDV, only EHDV-1 a...

  15. [Clinical and tomographic aspects of hemorrhagic cerebrovascular disease associated with hypertensive crisis in adults under 50 years of age].

    PubMed

    Arismendi-Morillo, G J; Fernández-Abreu, M; Añez-Moreno, R E

    2000-09-01

    The purpose of this study was to analyze both the clinical and tomographic aspects of the hemorrhagic cerebrovascular disease (HCd), associated with hypertensive crisis in adults under 50 years of age. Forty six patients, who were not under anticoagulant therapy, were not using illegal drugs, who had not a cerebral tumor disease, and who had neither arteriovenous malformations nor past traumatic episodes, were studied. Seventy eight percent of the patients had preexisted arterial hypertension, 30% of them had at least a previous emergency for a hypertensive crisis. Mortality for intracerebral hematoma (ICH) and for subarachnoid hemorrhage (SAH) was 21% and 23% respectively. In 68% of the cases, ICH was located in the deep structures of the brain. Asymmetric ventricular system, compression or the absence of mesencephalic cisterna were significantly associated (p > 0.01; p > 0.001 respectively) with higher mortality. There was not a significant difference between the deceased and the survivors in relation with their systolic and diastolic arterial pressure on admission to the emergency unit. A significant positive relation was found between the severity of the injury (percentage of patients with an Scale Coma Glasgow < or = 8 points) and the mortality percentage for the type of HCd (r = 0.81 for ICH; p < 0.001, r = 0.98 for SAH; p < 0.001). Age and a low Scale Coma Glasgow score on the admission, represent unfavorable prognostic factors. Due to the different criteria used to evaluate the tomographic characteristics of intracerebral hematomas, comparisons of the present results with other findings can be difficult. PMID:11029832

  16. Multiple efficacy studies of an adenovirus-vectored foot-and-mouth disease virus serotype A24 subunit vaccine in cattle using homologous challenge.

    PubMed

    Schutta, Christopher; Barrera, José; Pisano, Melia; Zsak, Laszlo; Grubman, Marvin J; Mayr, Gregory A; Moraes, Mauro P; Kamicker, Barbara J; Brake, David A; Ettyreddy, Damodar; Brough, Douglas E; Butman, Bryan T; Neilan, John G

    2016-06-01

    The safety and efficacy of an experimental, replication-deficient, human adenovirus-vectored foot-and-mouth disease virus (FMDV) serotype A24 Cruzeiro capsid-based subunit vaccine (AdtA24) was examined in eight independent cattle studies. AdtA24 non-adjuvanted vaccine was administered intramuscularly to a total of 150 steers in doses ranging from approximately 1.0×10(8) to 2.1×10(11) particle units per animal. No detectable local or systemic reactions were observed after vaccination. At 7 days post-vaccination (dpv), vaccinated and control animals were challenged with FMDV serotype A24 Cruzeiro via the intradermal lingual route. Vaccine efficacy was measured by FMDV A24 serum neutralizing titers and by protection from clinical disease and viremia after challenge. The results of eight studies demonstrated a strong correlation between AdtA24 vaccine dose and protection from clinical disease (R(2)=0.97) and viremia (R(2)=0.98). There was also a strong correlation between FMDV A24 neutralization titers on day of challenge and protection from clinical disease (R(2)=0.99). Vaccination with AdtA24 enabled differentiation of infected from vaccinated animals (DIVA) as demonstrated by the absence of antibodies to the FMDV nonstructural proteins in vaccinates prior to challenge. Lack of AdtA24 vaccine shedding after vaccination was indicated by the absence of neutralizing antibody titers to both the adenovector and FMDV A24 Cruzeiro in control animals after co-mingling with vaccinated cattle for three to four weeks. In summary, a non-adjuvanted AdtA24 experimental vaccine was shown to be safe, immunogenic, consistently protected cattle at 7 dpv against direct, homologous FMDV challenge, and enabled differentiation of infected from vaccinated cattle prior to challenge. PMID:26707216

  17. Surveillance for an emerging disease: dengue hemorrhagic fever in Puerto Rico, 1988-1997. Puerto Rico Association of Epidemiologists.

    PubMed

    Rigau-Pérez, J G

    1999-12-01

    Surveillance for emerging diseases is critically dependent on four factors: reporting methods, case definition, laboratory diagnosis, and knowledge of the disease among health-care professionals. The dengue hemorrhagic fever (DHF) surveillance system in Puerto Rico collects patient data from three sources: dengue case investigation (DCI) forms sent with diagnostic samples, clinical reports from hospital infection control nurses (ICNs), and hospital records. Recruitment of ICN reporting produced a marked increase in notifications (67 to 294). Hospital records of possible DHF cases showed that tests for ascertaining diagnosis (e.g., blood in stool, serum albumin) were frequently not performed. DCI and ICN reports underestimated severity. After hospital record review, the ratio of total DHF cases to cases detected by surveillance was approximately 3:1, whether using clinical criteria or using clinical and dengue laboratory diagnosis. An important determinant for the low sensitivity (28.4%) and high specificity (96.5%) of the surveillance system was the World Health Organization (WHO) clinical definition for DHF. In spite of such limitations, DHF surveillance data in Puerto Rico provide abundant, reliable information for monitoring disease trends. These methods may be applied to other situations to define the characteristics and incidence trends of emerging infections. PMID:10730300

  18. Genomic and bioinformatics analysis of HAdV-7, a human adenovirus of species B1 that causes acute respiratory disease: implications for vector development in human gene therapy.

    PubMed

    Purkayastha, Anjan; Su, Jing; Carlisle, Steve; Tibbetts, Clark; Seto, Donald

    2005-02-01

    Human adenovirus serotype 7 (HAdV-7) is a reemerging pathogen identified in acute respiratory disease (ARD), particularly in epidemics affecting basic military trainee populations of otherwise healthy young adults. The genome has been sequenced and annotated (GenBank accession no. ). Comparative genomics and bioinformatics analyses of the HAdV-7 genome sequence provide insight into its natural history and phylogenetic relationships. A putative origin of HAdV-7 from a chimpanzee host is observed. This has implications within the current biotechnological interest of using chimpanzee adenoviruses as vectors for human gene therapy and DNA vaccine delivery. Rapid genome sequencing and analyses of this species B1 member provide an example of exploiting accurate low-pass DNA sequencing technology in pathogen characterization and epidemic outbreak surveillance through the identification, validation, and application of unique pathogen genome signatures. PMID:15661145

  19. Re-emergent human adenovirus genome type 7d caused an acute respiratory disease outbreak in Southern China after a twenty-one year absence.

    PubMed

    Zhao, Suhui; Wan, Chengsong; Ke, Changwen; Seto, Jason; Dehghan, Shoaleh; Zou, Lirong; Zhou, Jie; Cheng, Zetao; Jing, Shuping; Zeng, Zhiwei; Zhang, Jing; Wan, Xuan; Wu, Xianbo; Zhao, Wei; Zhu, Li; Seto, Donald; Zhang, Qiwei

    2014-01-01

    Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed. PMID:25482188

  20. Rescue administration of a helper-dependent adenovirus vector with long-term efficacy in dogs with glycogen storage disease type Ia.

    PubMed

    Crane, B; Luo, X; Demaster, A; Williams, K D; Kozink, D M; Zhang, P; Brown, T T; Pinto, C R; Oka, K; Sun, F; Jackson, M W; Chan, L; Koeberl, D D

    2012-04-01

    Glycogen storage disease type Ia (GSD-Ia) stems from glucose-6-phosphatase (G6Pase) deficiency and causes hypoglycemia, hepatomegaly, hypercholesterolemia and lactic acidemia. Three dogs with GSD-Ia were initially treated with a helper-dependent adenovirus encoding a human G6Pase transgene (HDAd-cG6Pase serotype 5) on postnatal day 3. Unlike untreated dogs with GSD-Ia, all three dogs initially maintained normal blood glucose levels. After 6-22 months, vector-treated dogs developed hypoglycemia, anorexia and lethargy, suggesting that the HDAd-cG6Pase serotype 5 vector had lost efficacy. Liver biopsies collected at this time revealed significantly elevated hepatic G6Pase activity and reduced glycogen content, when compared with affected dogs treated only by frequent feeding. Subsequently, the HDAd-cG6Pase serotype 2 vector was administered to two dogs, and hypoglycemia was reversed; however, renal dysfunction and recurrent hypoglycemia complicated their management. Administration of a serotype 2 HDAd vector prolonged survival in one GSD-Ia dog to 12 months of age and 36 months of age in the other, but the persistence of long-term complications limited HDAd vectors in the canine model for GSD-Ia. PMID:21654821

  1. Re-emergent Human Adenovirus Genome Type 7d Caused an Acute Respiratory Disease Outbreak in Southern China After a Twenty-one Year Absence

    PubMed Central

    Zhao, Suhui; Wan, Chengsong; Ke, Changwen; Seto, Jason; Dehghan, Shoaleh; Zou, Lirong; Zhou, Jie; Cheng, Zetao; Jing, Shuping; Zeng, Zhiwei; Zhang, Jing; Wan, Xuan; Wu, Xianbo; Zhao, Wei; Zhu, Li; Seto, Donald; Zhang, Qiwei

    2014-01-01

    Human adenoviruses (HAdVs) are highly contagious pathogens causing acute respiratory disease (ARD), among other illnesses. Of the ARD genotypes, HAdV-7 presents with more severe morbidity and higher mortality than the others. We report the isolation and identification of a genome type HAdV-7d (DG01_2011) from a recent outbreak in Southern China. Genome sequencing, phylogenetic analysis, and restriction endonuclease analysis (REA) comparisons with past pathogens indicate HAdV-7d has re-emerged in Southern China after an absence of twenty-one years. Recombination analysis reveals this genome differs from the 1950s-era prototype and vaccine strains by a lateral gene transfer, substituting the coding region for the L1 52/55 kDa DNA packaging protein from HAdV-16. DG01_2011 descends from both a strain circulating in Southwestern China (2010) and a strain from Shaanxi causing a fatality and outbreak (Northwestern China; 2009). Due to the higher morbidity and mortality rates associated with HAdV-7, the surveillance, identification, and characterization of these strains in population-dense China by REA and/or whole genome sequencing are strongly indicated. With these accurate identifications of specific HAdV types and an epidemiological database of regional HAdV pathogens, along with the HAdV genome stability noted across time and space, the development, availability, and deployment of appropriate vaccines are needed. PMID:25482188

  2. Infliximab therapy for Crohn’s-like disease in common variable immunodeficiency complicated by massive intestinal hemorrhage: a case report

    PubMed Central

    2014-01-01

    Background Common variable immune deficiency is the most frequently encountered immunodeficiency in adults, which is characterized by low levels of serum immunoglobulins. Common variable immune deficiency can present with inflammatory bowel disease-like colitis because of the dysregulated immune system; paradoxically activated T cell receptor pathways are thought to be pivotal in pathogenesis of common variable immune deficiency-related colitis. Treatment for severe complications, such as gastrointestinal bleeding, is not established. We report a case of common variable immune deficiency-related Crohn’s-like disease presenting massive melena, which was successfully treated by short course infliximab therapy. Case presentation A 26-year-old Japanese man with history of common variable immune deficiency presented with diarrhea, abdominal pain, and fever. Venous administration of antibiotics did not improve his symptoms. Colonoscopy revealed multiple longitudinal ulcers as well as cobblestone-like change in the ileum end and the ascending colon. Histopathological examination of biopsy specimen showed erosion and infiltration of T lymphocytes with lack of B cells. Intravenous hyperalimentation, mesalazine, and steroid did not improve the symptoms and the patient subsequently presented with massive melena. Colonoscopy revealed a protuberant vessel on one of the ulcers in the ascending colon. Endoscopic clipping was repeatedly performed for hemostasis, which was only temporarily successful. In an attempt to manage the bleeding and colitis, a trial of infliximab was given on week 0, week 2 and week 6. Gastrointestinal hemorrhage from the ulcer halted immediately after the first infliximab injection. Colonoscopy performed after the third infliximab showed remarkable improvement in the ileocolitis. No evidence of increased susceptibility to infections was observed and the patient has been in clinical remission for 3 years. Conclusions We present this case together with

  3. Subarachnoid hemorrhage

    MedlinePlus

    ... injury leading to subarachnoid hemorrhage is motor vehicle crashes. Risks include: Aneurysm in other blood vessels Fibromuscular ... lumbar puncture ( spinal tap ) may be done. Other tests that may be done include: Cerebral angiography of ...

  4. Subarachnoid Hemorrhage

    MedlinePlus

    ... can result from the rupture of an intracranial aneurysm — a weakened, dilated area of a blood vessel ... blood vessels in the brain even after the aneurysm that caused the hemorrhage is treated. Most of ...

  5. Subarachnoid hemorrhage

    MedlinePlus

    ... malformation (AVM) Bleeding disorder Bleeding from a cerebral aneurysm Head injury Unknown cause (idiopathic) Use of blood ... subarachnoid hemorrhage is motor vehicle crashes. Risks include: Aneurysm in other blood vessels Fibromuscular dysplasia (FMD) and ...

  6. EPIZOOTIC HEMORRHAGIC DISEASE: ANALYSIS OF TISSUES BY AMPLIFICATION AND IN SITU HYBRIDIZATION REVEALS WIDESPREAD ORBIVIRUS INFECTION AT LOW COPY NUMBERS

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A recent outbreak of hemorrhagic fever in wild ruminants in the northwest United States was characterized by rapid onset of fever, followed shortly thereafter by hemorrhage and death. As a result, a confirmed 1,000 white-tailed deer and pronghorn antelope died over the course of 3 months. Lesions we...

  7. Prion Protein-Hemin Interaction Upregulates Hemoglobin Synthesis: Implications for Cerebral Hemorrhage and Sporadic Creutzfeldt-Jakob Disease.

    PubMed

    Tripathi, Ajai K; Singh, Neena

    2016-01-01

    Hemin is known to induce endocytosis of prion-protein (PrP(C)) from the neuronal plasma membrane, potentially limiting propagation of the disease causing PrP-scrapie (PrP(Sc)) isoform. Hemin is therefore an attractive disease-modifying option for sporadic Creutzfeldt-Jakob disease (sCJD), a human prion disorder with no effective treatment. The hemin-PrP(C) interaction is also of interest in cerebral-hemorrhage (CH), a condition where potentially toxic hemin molecules come in contact with neuronal PrP(C). Interestingly, PrP(C) is upregulated in penumbric neurons surrounding CH and is known to confer neuroprotection in a dose-dependent manner. The underlying mechanism, however, is not clear. Here, we report that hemin binds PrP(C) on diverse cell lines, resulting in its aggregation or degradation in a cell-type specific manner. Surprisingly, the hemin-PrP(C) interaction upregulates Hb synthesis in hematopoietic cells, a response reversed by deleting the hemin-binding octa-peptide repeat region of PrP(C). A similar response is noted in brain organotypic cultures where exposure to hemin induces significantly more α-globin in wild-type (PrP(+/+)) relative to PrP-knock-out (PrP(-/-)) samples. Furthermore, red blood cells and brain tissue from PrP(-/-) mice show significantly less α-globin relative to PrP(+/+) controls, indicating a positive effect of PrP(C) on Hb synthesis under physiological conditions as well. Surprisingly, levels of α-globin are significantly higher in sCJD brain tissue relative to controls, suggesting compensatory upregulation of Hb synthesis by surviving neurons or misregulation in diseased brains. These observations reveal a unique function of PrP(C) that is likely to impact the therapeutic management of CH and sCJD. PMID:26836195

  8. Identification and characterization of a novel adenovirus in the cloacal bursa of gulls

    SciTech Connect

    Bodewes, R.; Bildt, M.W.G. van de; Schapendonk, C.M.E.; Leeuwen, M. van; Boheemen, S. van; Jong, A.A.W. de; Osterhaus, A.D.M.E.; Smits, S.L.; Kuiken, T.

    2013-05-25

    Several viruses of the family of Adenoviridae are associated with disease in birds. Here we report the detection of a novel adenovirus in the cloacal bursa of herring gulls (Larus argentatus) and lesser black-backed gulls (Larus fuscus) that were found dead in the Netherlands in 2001. Histopathological analysis of the cloacal bursa revealed cytomegaly and karyomegaly with basophilic intranuclear inclusions typical for adenovirus infection. The presence of an adenovirus was confirmed by electron microscopy. By random PCR in combination with deep sequencing, sequences were detected that had the best hit with known adenoviruses. Phylogenetic analysis of complete coding sequences of the hexon, penton and polymerase genes indicates that this novel virus, tentatively named Gull adenovirus, belongs to the genus Aviadenovirus. The present study demonstrates that birds of the Laridae family are infected by family-specific adenoviruses that differ from known adenoviruses in other bird species. - Highlights: ► Lesions typical for adenovirus infection detected in cloacal bursa of dead gulls. ► Confirmation of adenovirus infection by electron microscopy and deep sequencing. ► Sequence analysis indicates that it is a novel adenovirus in the genus Aviadenovirus. ► The novel (Gull) adenovirus was detected in multiple organs of two species of gulls.

  9. Control of foot-and-mouth disease by using replication-defective human adenoviruses to deliver vaccines and biotherapeutics

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Foot-and-mouth disease (FMD) is one of the most contagious viral diseases that can affect cloven-hoofed livestock and wild animals. Outbreaks of FMD have caused devastating economic losses and the slaughter of millions of animals in many regions of the world affecting the food chain and global devel...

  10. Pontine infarcts and hemorrhages.

    PubMed

    Moncayo, Jorge

    2012-01-01

    Pontine infarcts are often part of a large ischemia involving the brainstem, although infarcts may be restricted to the pons. In both cases, infarcts in the pons are characterized by interesting clinical patterns resulting from a variety of cranial nerve dysfunctions, eye movement disorders and motor, sensory and cerebellar manifestations, either isolated or in combination. The anteromedial and anterolateral territories are the most commonly involved. Penetrating branch artery disease is the most common etiology. Ten percent of all intracerebral hemorrhages are located in the pons, and small hemorrhages in this brainstem structure may, in some instances, give rise to unusual clinical manifestations. PMID:22377887

  11. Characterization of group II avian adenoviruses with a panel of monoclonal antibodies.

    PubMed Central

    van den Hurk, J V; van Drunen Littel-van den Hurk, S

    1988-01-01

    The interaction between a panel of ten monoclonal antibodies and hemorrhagic enteritis virus, a group II avian adenovirus, was determined. The monoclonal antibodies reacted with all nine isolates of group II avian adenoviruses, but not with any of five types of group I avian adenoviruses. All ten monoclonal antibodies recognized antigenic determinants on the hexon protein of hemorrhagic enteritis virus when analyzed by immunoprecipitation and immunoblotting. They reacted only with the native hexon protein and not with protein denatured by sodium dodecyl sulfate or guanidine-HCl/urea treatment combined with reduction and carboxymethylation. Based on the results of competitive binding assays, the panel of monoclonal antibodies could be subdivided into two groups, which recognized different antigenic domains of the hemorrhagic enteritis virus hexon protein. The monoclonal antibodies in group 1 neutralized hemorrhagic enteritis virus infectivity while the monoclonal antibodies of group 2 did not. Group 1 consisted of eight monoclonal antibodies which could be further subdivided into subgroups 1A, 1B, 1C and 1D. The subdivision of the monoclonal antibodies was based on the degree of blocking in the competitive binding assays and differences in their ability to induce enhancement. In general, the monoclonal antibodies had a higher avidity for the virulent isolate of hemorrhagic enteritis virus than for the avirulent hemorrhagic enteritis virus isolate. Images Fig. 1. Fig. 2. Fig. 4. PMID:2461793

  12. Production, Characterization, and Epitope Mapping of Monoclonal Antibodies Against Different Subtypes of Rabbit Hemorrhagic Disease Virus (RHDV)

    PubMed Central

    Kong, Desheng; Liu, Jiasen; Jiang, Qian; Yu, Zuo; Hu, Xiaoliang; Guo, Dongchun; Huang, Qianqian; Jiao, Meihui; Qu, Liandong

    2016-01-01

    In 2010, a new rabbit hemorrhagic disease virus (RHDV) variant, designated RHDV2, was identified for the first time in Italy. Studies have shown that RHDV2 differs from RHDV1 (traditional RHDV) in terms of its antigenic profile and genetic characteristics. The VP60 protein of RHDV is a structural protein that plays important roles in viral replication, assembly, and immunogenicity. In this study, we immunized BALB/c mice with recombinant VP60 proteins from different RHDV subtypes. After three rounds of subcloning, type-specific positive hybridoma clones of RHDV1 and RHDV2 were further identified by an enzyme-linked immunosorbent assay, Western blotting, and an indirect immunofluorescence assay. Finally, three monoclonal antibodies (MAbs) (1D6, 1H2, and 3F2) that only recognize RHDV1, and four MAbs (1G2, 2C1, 3B7, and 5D6) that only recognize RHDV2 were identified. The epitopes recognized by these MAbs were mapped by Western blotting. Sequence analysis showed that the epitope sequences recognized by 1D6, 1H2, and 3F2 are highly conserved (98%) among RHDV1 strains, whereas the epitope sequences recognized by 1G2, 2C1, 3B7, and 5D6 are 100% conserved among RHDV2 strains. The high conservation of the epitope sequence showed that the screened MAbs were type-specific, and that they could distinguish different RHDV subtypes. PMID:26878800

  13. Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses

    PubMed Central

    Moreno, Noelia; Mena, Ignacio; Angulo, Iván; Gómez, Yolanda; Crisci, Elisa; Montoya, María; Castón, José R.; Blanco, Esther; Bárcena, Juan

    2016-01-01

    Virus-like particles (VLPs), comprised of viral structural proteins devoid of genetic material, are tunable nanoparticles that can be chemically or genetically engineered, to be used as platforms for multimeric display of foreign antigens. Here, we report the engineering of chimeric VLPs, derived from rabbit hemorrhagic disease virus (RHDV) for presentation of foreign B-cell antigens to the immune system. The RHDV capsid comprises 180 copies of a single capsid subunit (VP60). To evaluate the ability of chimeric RHDV VLPs to elicit protective humoral responses against foreign antigens, we tested two B-cell epitopes: a novel neutralizing B-cell epitope, derived from feline calicivirus capsid protein, and a well characterized B-cell epitope from the extracellular domain of influenza A virus M2 protein (M2e). We generated sets of chimeric RHDV VLPs by insertion of the foreign B-cell epitopes at three different locations within VP60 protein (which involved different levels of surface accessibility) and in different copy numbers per site. The immunogenic potential of the chimeric VLPs was analyzed in the mouse model. The results presented here indicated that chimeric RHDV VLPs elicit potent protective humoral responses against displayed foreign B-cell epitopes, demonstrated by both, in vitro neutralization and in vivo protection against a lethal challenge. PMID:27549017

  14. Identification of bluetongue virus and epizootic hemorrhagic disease virus serotypes in French Guiana in 2011 and 2012.

    PubMed

    Viarouge, Cyril; Lancelot, Renaud; Rives, Germain; Bréard, Emmanuel; Miller, Manuelle; Baudrimont, Xavier; Doceul, Virginie; Vitour, Damien; Zientara, Stéphan; Sailleau, Corinne

    2014-11-01

    In French Guiana, the sero- and viro-prevalence of Bluetongue virus (BTV) is high but the circulating serotypes remain unknown. No data are available regarding the prevalence of Epizootic hemorrhagic disease (EHD). This study was conducted to assess the prevalence and to identify the circulating serotypes of these two Orbiviruses in this region (BTV and EHDV). Blood samples were collected in main livestock areas, from 122 young cattle between June and August 2011, to perform virological (PCR and viral isolation) and serological (ELISA) analyses. Moreover, samples from sheep and goat showing BTV-like clinical signs and from newly imported animals were analyzed using the same assays. Results confirmed an important viral circulation, with viro- and seroprevalence of 85% and 84% and 60% and 40% for BTV and EHDV, respectively. Ten Orbivirus serotypes were identified (BTV-1, 2, 6, 10, 12, 13, 17 and 24, EHDV-1 and 6). The circulation of many serotypes in intertropical America and in the Caribbean region underlines the need to establish measures to monitor and control animal movements. PMID:25301282

  15. Rabbit hemorrhagic disease virus capsid, a versatile platform for foreign B-cell epitope display inducing protective humoral immune responses.

    PubMed

    Moreno, Noelia; Mena, Ignacio; Angulo, Iván; Gómez, Yolanda; Crisci, Elisa; Montoya, María; Castón, José R; Blanco, Esther; Bárcena, Juan

    2016-01-01

    Virus-like particles (VLPs), comprised of viral structural proteins devoid of genetic material, are tunable nanoparticles that can be chemically or genetically engineered, to be used as platforms for multimeric display of foreign antigens. Here, we report the engineering of chimeric VLPs, derived from rabbit hemorrhagic disease virus (RHDV) for presentation of foreign B-cell antigens to the immune system. The RHDV capsid comprises 180 copies of a single capsid subunit (VP60). To evaluate the ability of chimeric RHDV VLPs to elicit protective humoral responses against foreign antigens, we tested two B-cell epitopes: a novel neutralizing B-cell epitope, derived from feline calicivirus capsid protein, and a well characterized B-cell epitope from the extracellular domain of influenza A virus M2 protein (M2e). We generated sets of chimeric RHDV VLPs by insertion of the foreign B-cell epitopes at three different locations within VP60 protein (which involved different levels of surface accessibility) and in different copy numbers per site. The immunogenic potential of the chimeric VLPs was analyzed in the mouse model. The results presented here indicated that chimeric RHDV VLPs elicit potent protective humoral responses against displayed foreign B-cell epitopes, demonstrated by both, in vitro neutralization and in vivo protection against a lethal challenge. PMID:27549017

  16. Adenovirus: Epidemiology, Global Spread of Novel Serotypes, and Advances in Treatment and Prevention.

    PubMed

    Lynch, Joseph P; Kajon, Adriana E

    2016-08-01

    Adenoviruses (AdVs) are DNA viruses that typically cause mild infections involving the upper or lower respiratory tract, gastrointestinal tract, or conjunctiva. Rare manifestations of AdV infections include hemorrhagic cystitis, hepatitis, hemorrhagic colitis, pancreatitis, nephritis, or meningoencephalitis. AdV infections are more common in young children, due to lack of humoral immunity. Epidemics of AdV infection may occur in healthy children or adults in closed or crowded settings (particularly military recruits). The disease is more severe and dissemination is more likely in patients with impaired immunity (e.g., organ transplant recipients, human immunodeficiency virus infection). Fatality rates for untreated severe AdV pneumonia or disseminated disease may exceed 50%. More than 50 serotypes of AdV have been identified. Different serotypes display different tissue tropisms that correlate with clinical manifestations of infection. The predominant serotypes circulating at a given time differ among countries or regions, and change over time. Transmission of novel strains between countries or across continents and replacement of dominant viruses by new strains may occur. Treatment of AdV infections is controversial, as prospective, randomized therapeutic trials have not been conducted. Cidofovir is the drug of choice for severe AdV infections, but not all patients require treatment. Live oral vaccines are highly efficacious in reducing the risk of respiratory AdV infection and are in routine use in the military in the United States, but currently are not available to civilians. PMID:27486739

  17. Structure of human adenovirus

    SciTech Connect

    Nemerow, Glen R.; Stewart, Phoebe L.; Reddy, Vijay S.

    2012-07-11

    A detailed structural analysis of the entire human adenovirus capsid has been stymied by the complexity and size of this 150 MDa macromolecular complex. Over the past 10 years, the steady improvements in viral genome manipulation concomitant with advances in crystallographic techniques and data processing software has allowed structure determination of this virus by X-ray diffraction at 3.5 {angstrom} resolution. The virus structure revealed the location, folds, and interactions of major and minor (cement proteins) on the inner and outer capsid surface. This new structural information sheds further light on the process of adenovirus capsid assembly and virus-host cell interactions.

  18. Anti-Tumor Effects of an Oncolytic Adenovirus Expressing Hemagglutinin-Neuraminidase of Newcastle Disease Virus in Vitro and in Vivo

    PubMed Central

    He, Dongyun; Sun, Lili; Li, Chang; Hu, Ningning; Sheng, Yuan; Chen, Zhifei; Li, Xiao; Chi, Baorong; Jin, Ningyi

    2014-01-01

    Oncolytic virotherapy has been an attractive drug platform for targeted therapy of cancer over the past few years. Viral vectors can be used to target and lyse cancer cells, but achieving good efficacy and specificity with this treatment approach is a major challenge. Here, we assessed the ability of a novel dual-specific anti-tumor oncolytic adenovirus, expressing the hemagglutinin-neuraminidase (HN) gene from the Newcastle disease virus under the human telomerase reverse transcriptase (hTERT) promoter (Ad-hTERTp-E1a-HN), to inhibit esophageal cancer EC-109 cells in culture and to reduce tumor burden in xenografted BALB/c nude mice. In vitro, infection with Ad-hTERT-E1a-HN could inhibit the growth of EC-109 cells significantly and also protect normal human liver cell line L02 from growth suppression in 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays. Ad-hTERT-E1a-HN also effectively and selectively decreased the sialic acid level on EC-109 cells, but not on L02 cells. Furthermore, Ad-hTERT-E1a-HN was shown to induce the apoptosis pathway via acridine orange and ethidium bromide staining (AO/EB staining), increase reactive oxygen species (ROS), reduce mitochondrial membrane potential and release cytochrome c. In vivo, xenografted BALB/c nude mice were treated via intratumoral or intravenous injections of Ad-hTERT-E1a-HN. Although both treatments showed an obvious suppression in tumor volume, only Ad-hTERT-E1a-HN delivered via intratumoral injection elicited a complete response to treatment. These results reinforced previous findings and highlighted the potential therapeutic application of Ad-hTERT-E1a-HN for treatment of esophageal cancer in clinical trials. PMID:24553109

  19. Mesenchymal stromal cell therapy is associated with increased adenovirus-associated but not cytomegalovirus-associated mortality in children with severe acute graft-versus-host disease.

    PubMed

    Calkoen, Friso G J; Vervat, Carly; van Halteren, Astrid G S; Welters, Marij J P; Veltrop-Duits, Louise A; Lankester, Arjan C; Egeler, R Maarten; Ball, Lynne M; van Tol, Maarten J D

    2014-08-01

    Beneficial effects of mesenchymal stromal cells (MSCs) in patients with severe steroid-refractory acute graft-versus-host disease (aGvHD) have been reported. However, controversy exists about the effect of MSCs on virus-specific T cells. We evaluated 56 patients with grade II-IV aGvHD who responded to steroids (n = 21) or were steroid refractory receiving either MSCs (n = 22) or other second-line therapy (n = 13). Although the overall incidence of cytomegalovirus (CMV), Epstein-Barr virus, and human adenovirus (HAdV) infections was not significantly increased, HAdV infection was associated with decreased survival in children treated with MSCs. Thus, we investigated in vitro the effects of MSCs on virus-specific T cells. Both CMV-specific and, to a lesser extent, HAdV-specific T-cell activation and proliferation were negatively affected by MSCs either after induction of a response in peripheral blood mononuclear cells (PBMCs) or after restimulation of virus-specific T-cell lines. In patient-derived PBMCs, CMV-specific proliferative responses were greatly decreased on first-line treatment of aGvHD with systemic steroids and slowly recovered after MSC administration and tapering of steroids. HAdV-specific T-cell proliferation could not be detected. In contrast, the proportion of CMV- and HAdV-specific effector T cells, measured as interferon-γ-secreting cells, remained stable or increased after treatment with MSCs. In conclusion, although in vitro experimental conditions indicated a negative impact of MSCs on CMV- and HAdV-specific T-cell responses, no solid evidence was obtained to support such an effect of MSCs on T-cell responses in vivo. Still, the susceptibility of steroid-refractory severe aGvHD patients to viral reactivation warrants critical viral monitoring during randomized controlled trials on second-line treatment including MSCs. PMID:24904175

  20. Autophagic response in the Rabbit Hemorrhagic Disease, an animal model of virally-induced fulminant hepatic failure

    PubMed Central

    2014-01-01

    The Rabbit Hemorrhagic Disease Virus (RHDV) induces a severe disease that fulfils many requirements of an animal model of fulminant hepatic failure. However, a better knowledge of molecular mechanisms contributing to liver damage is required, and it is unknown whether the RHDV induces liver autophagy and how it relates to apoptosis. In this study, we attempted to explore which signalling pathways were involved in the autophagic response induced by the RHDV and to characterize their role in the context of RHDV pathogenesis. Rabbits were infected with 2 × 104 hemmaglutination units of a RHDV isolate. The autophagic response was measured as presence of autophagic vesicles, LC3 staining, conversion of LC3-I to autophagosome-associated LC3-II and changes in expression of beclin-1, UVRAG, Atg5, Atg12, Atg16L1 and p62/SQSTM1. RHDV-triggered autophagy reached a maximum at 24 hours post-infection (hpi) and declined at 30 and 36 hpi. Phosphorylation of mTOR also augmented in early periods of infection and there was an increase in the expression of the endoplasmic reticulum chaperones BiP/GRP78, CHOP and GRP94. Apoptosis, measured as caspase-3 activity and expression of PARP-1, increased significantly at 30 and 36 hpi in parallel to the maximal expression of the RHDV capsid protein VP60. These data indicate that RHDV infection initiates a rapid autophagic response, perhaps in an attempt to protect liver, which associates to ER stress development and is independent from downregulation of the major autophagy suppressor mTOR. As the infection continues and the autophagic response declines, cells begin to exhibit apoptosis. PMID:24490870

  1. Increased efficacy of an adenovirus-vectored foot-and-mouth disease capsid subunit vaccine expressing nonstructural protein 2B is associated with a specific T cell response

    Technology Transfer Automated Retrieval System (TEKTRAN)

    We previously demonstrated that an adenovirus-based FMDV serotype A24 subunit vaccine, Ad5-A24, expressed under the control of a cytomegalovirus promoter (CMV) can protect swine and bovines against homologous challenge, but swine vaccinated with an Ad5-vectored FMDV O1 Campos vaccine, Ad5-O1Campos (...

  2. Adenovirus-Mediated Expression of Interferon-Alpha Delays Viral Replication and Reduces Disease Signs in Swine Challenged with Porcine Reproductive and Respiratory Syndrome Virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this study, pigs were injected with a nonreplicating human adenovirus type 5 vector expressing porcine interferon-alpha (Ad5-pIFNa) and then challenged with porcine reproductive and respiratory syndrome virus (PRRSV) to determine whether the presence of increased levels of IFNa would decrease vir...

  3. Spontaneous retroperitoneal hemorrhage presenting as hemoperitoneum secondary to renal cyst rupture in a peritoneal dialysis patient with acquired cystic kidney disease.

    PubMed

    Biyik, Z; Solak, Y; Gaipov, A; Ozbek, O; Esen, H; Turk, S

    2015-01-01

    Spontaneous retroperitoneal hemorrhage (SRH) is a rare and potentially fatal condition. Acquired cystic kidney disease (ACKD) may cause SRH in hemodialysis patients. However, presentation of retroperitoneal hematoma as hemoperitoneum in peritoneal dialysis (PD) patients is exceedingly rare. We report a 44-year-old male PD patient who presented with hemoperitoneum secondary to retroperitoneal hematoma. The reason of SRH was rupture of the cysts of ACKD. The patient underwent unilateral nephrectomy with subsequent disappearance of hemoperitoneum. The importance of this case lies in the fact that the patients who have been receiving dialysis for a long time should be under surveillance in terms of ACKD development and potential associated complications such as cyst hemorrhage and malignancy. PMID:26199480

  4. Elevated Cellular Retinoic Acid Binding Protein-I in Cerebrospinal Fluid of Patients with Hemorrhagic Cerebrovascular Diseases : Preliminary Study

    PubMed Central

    Jeon, Jin Pyeong; Cho, Won-Sang; Kang, Hyun-Seung; Kim, Seung-Ki; Oh, Chang Wan

    2015-01-01

    Objective Elevated cellular retinoic acid binding protein-I (CRABP-I) is thought to be related to the abnormal proliferation and migration of smooth muscle cells (SMCs). Accordingly, a higher CRABP-I level could cause disorganized vessel walls by causing immature SMC phenotypes and altering extracellular matrix proteins which could result in vulnerable arterial walls with inadequate responses to hemodynamic stress. We hypothesized that elevated CRABP-I level in the cerebrospinal fluid (CSF) could be related to subarachnoid hemorrhage (SAH). Moreover, we also extended this hypothesis in patients with vascular malformation according to the presence of hemorrhage. Methods We investigated the CSF of 26 patients : SAH, n=7; unruptured intracranial aneurysm (UIA), n=7; arteriovenous malformation (AVM), n=4; cavernous malformation (CM), n=3; control group, n=5. The optical density of CRABP-I was confirmed by Western blotting and presented as mean±standard error of the measurement. Results CRABP-I in SAH (0.33±0.09) was significantly higher than that in the UIA (0.12±0.01, p=0.033) or control group (0.10±0.01, p=0.012). Hemorrhage presenting AVM (mean 0.45, ranged 0.30-0.59) had a higher CRABP-I level than that in AVM without hemorrhage presentation (mean 0.16, ranged 0.14-0.17). The CRABP-I intensity in CM with hemorrhage was 0.21 and 0.31, and for CM without hemorrhage 0.14. Overall, the hemorrhage presenting group (n=11, 0.34±0.06) showed a significantly higher CRABP-I intensity than that of the non-hemorrhage presenting group (n=10, 0.13±0.01, p=0.001). Conclusion The results suggest that elevated CRABP-I in the CSF could be related with aneurysm rupture. Additionally, a higher CRABP-I level seems to be associated with hemorrhage development in vascular malformation. PMID:25733988

  5. Phylogenetic and pathogenic characterization of novel adenoviruses from long-tailed ducks (Clangula hyemalis)

    USGS Publications Warehouse

    Counihan, Katrina; Skerratt, Lee; Franson, J. Christian; Hollmen, Tuula E.

    2015-01-01

    Novel adenoviruses were isolated from a long-tailed duck (Clangula hyemalis) mortality event near Prudhoe Bay, Alaska in 2000. The long-tailed duck adenovirus genome was approximately 27 kb. A 907 bp hexon gene segment was used to design primers specific for the long-tailed duck adenovirus. Nineteen isolates were phylogenetically characterized based on portions of their hexon gene and 12 were most closely related to Goose adenovirus A. The remaining 7 shared no hexon sequences with any known adenoviruses. Experimental infections of mallards with a long-tailed duck reference adenovirus caused mild lymphoid infiltration of the intestine and paint brush hemorrhages of the mucosa and dilation of the intestine. This study shows novel adenoviruses from long-tailed ducks are diverse and provides further evidence that they should be considered in cases of morbidity and mortality in sea ducks. Conserved and specific primers have been developed that will help screen sea ducks for adenoviral infections.

  6. Co-factor activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1996-08-06

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  7. Co-factor activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, C.W.; Mangel, W.F.

    1996-08-06

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying the peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  8. Pathogenesis of arenavirus hemorrhagic fevers.

    PubMed

    Moraz, Marie-Laurence; Kunz, Stefan

    2011-01-01

    Viral hemorrhagic fevers (VHFs) caused by arenaviruses belong to the most devastating emerging human diseases and represent serious public health problems. Arenavirus VHFs in humans are acute diseases characterized by fever and, in severe cases, different degrees of hemorrhages associated with a shock syndrome in the terminal stage. Over the past years, much has been learned about the pathogenesis of arenaviruses at the cellular level, in particular their ability to subvert the host cell's innate antiviral defenses. Clinical studies and novel animal models have provided important new information about the interaction of hemorrhagic arenaviruses with the host's adaptive immune system, in particular virus-induced immunosuppression, and have provided the first hints towards an understanding of the terminal hemorrhagic shock syndrome. The scope of this article is to review our current knowledge on arenavirus VHF pathogenesis with an emphasis on recent developments. PMID:21171877

  9. Imaging of adrenal and renal hemorrhage.

    PubMed

    Hammond, Nancy A; Lostumbo, Antonella; Adam, Sharon Z; Remer, Erick M; Nikolaidis, Paul; Yaghmai, Vahid; Berggruen, Senta M; Miller, Frank H

    2015-10-01

    Hemorrhage of the kidneys and adrenal glands has many etiologies. In the adrenal glands, trauma, anticoagulation, stress, sepsis, surgery, and neoplasms are common causes of hemorrhage. In the kidneys, reasons for hemorrhage include trauma, bleeding diathesis, vascular diseases, infection, infarction, hemorrhagic cyst rupture, the Antopol-Goldman lesion, and neoplasms. Angiomyolipoma and renal cell carcinoma are the neoplasms most commonly associated with hemorrhage in the kidneys and adrenal cortical carcinoma, metastases, and pheochromocytoma are associated with hemorrhage in the adrenal glands. Understanding the computed tomography and magnetic resonance imaging features, and causes of hemorrhage in the kidneys and adrenal glands is critical. It is also important to keep in mind that mimickers of hemorrhage exist, including lymphoma in both the kidneys and adrenal glands, and melanoma metastases in the adrenal glands. Appropriate imaging follow-up of renal and adrenal hemorrhage should occur to exclude an underlying malignancy as the cause. If there is suspicion for malignancy that cannot be definitively diagnosed on imaging, surgery or biopsy may be warranted. Angiography may be indicated when there is a suspected underlying vascular disease. Unnecessary intervention, such as nephrectomy, may be avoided in patients with benign causes or no underlying disease. Appropriate management is dependent on accurate diagnosis of the cause of renal or adrenal hemorrhage and it is incumbent upon the radiologist to determine the etiology. PMID:26036792

  10. Dengue and Dengue Hemorrhagic Fever

    PubMed Central

    Gubler, Duane J.

    1998-01-01

    Dengue fever, a very old disease, has reemerged in the past 20 years with an expanded geographic distribution of both the viruses and the mosquito vectors, increased epidemic activity, the development of hyperendemicity (the cocirculation of multiple serotypes), and the emergence of dengue hemorrhagic fever in new geographic regions. In 1998 this mosquito-borne disease is the most important tropical infectious disease after malaria, with an estimated 100 million cases of dengue fever, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually. The reasons for this resurgence and emergence of dengue hemorrhagic fever in the waning years of the 20th century are complex and not fully understood, but demographic, societal, and public health infrastructure changes in the past 30 years have contributed greatly. This paper reviews the changing epidemiology of dengue and dengue hemorrhagic fever by geographic region, the natural history and transmission cycles, clinical diagnosis of both dengue fever and dengue hemorrhagic fever, serologic and virologic laboratory diagnoses, pathogenesis, surveillance, prevention, and control. A major challenge for public health officials in all tropical areas of the world is to devleop and implement sustainable prevention and control programs that will reverse the trend of emergent dengue hemorrhagic fever. PMID:9665979

  11. Recombinant soluble adenovirus receptor

    DOEpatents

    Freimuth, Paul I.

    2002-01-01

    Disclosed are isolated polypeptides from human CAR (coxsackievirus and adenovirus receptor) protein which bind adenovirus. Specifically disclosed are amino acid sequences which corresponds to adenovirus binding domain D1 and the entire extracellular domain of human CAR protein comprising D1 and D2. In other aspects, the disclosure relates to nucleic acid sequences encoding these domains as well as expression vectors which encode the domains and bacterial cells containing such vectors. Also disclosed is an isolated fusion protein comprised of the D1 polypeptide sequence fused to a polypeptide sequence which facilitates folding of D1 into a functional, soluble domain when expressed in bacteria. The functional D1 domain finds application for example in a therapeutic method for treating a patient infected with a virus which binds to D1, and also in a method for identifying an antiviral compound which interferes with viral attachment. Also included is a method for specifically targeting a cell for infection by a virus which binds to D1.

  12. History of the restoration of adenovirus type 4 and type 7 vaccine, live oral (Adenovirus Vaccine) in the context of the Department of Defense acquisition system.

    PubMed

    Hoke, Charles H; Snyder, Clifford E

    2013-03-15

    Respiratory pathogens cause morbidity and mortality in US military basic trainees. Following the influenza pandemic of 1918, and stimulated by WWII, the need to protect military personnel against epidemic respiratory disease was evident. Over several decades, the US military elucidated etiologies of acute respiratory diseases and invented and deployed vaccines to prevent disease caused by influenza, meningococcus, and adenoviruses. In 1994, the Adenovirus Vaccine manufacturer stopped its production. By 1999, supplies were exhausted and adenovirus-associated disease, especially serotype 4-associated febrile respiratory illness, returned to basic training installations. Advisory bodies persuaded Department of Defense leaders to initiate restoration of Adenovirus Vaccine. In 2011, after 10 years of effort by government and contractor personnel and at a cost of about $100 million, the Adenovirus Vaccine was restored to use at all military basic training installations. Disease and adenovirus serotype 4 isolation rates have fallen dramatically since vaccinations resumed in October 2011 and remain very low. Mindful of the adage that "The more successful a vaccine is, the more quickly the need for it will be forgotten.", sustainment of the supply of the Adenovirus Vaccine may be a challenge, and careful management will be required for such sustainment. PMID:23291475

  13. A cross-sectional study of the association between risk factors and hemorrhagic disease of grass carp in ponds in Southern China.

    PubMed

    Yang, Song; Wu, Shuqin; Li, Ningqiu; Shi, Cunbin; Deng, Guocheng; Wang, Qing; Zeng, Weiwei; Lin, Qiang

    2013-12-01

    A cross-sectional survey of 215 Grass Carp Ctenopharyngodon idella ponds was conducted in southern China between May 2010 and November 2011. An in-depth questionnaire was developed to evaluate a series of biosecurity practices, environmental factors, and management factors at the farm level. Fish samples with clinical hemorrhagic signs were also collected from each pond to assess the clinical disease of Grass Carp reovirus by using reverse transcription (RT) PCR assay. The association between the incidence of Grass Carp hemorrhagic disease (GCHD) and risk factors was analyzed using logistic regression. Of the 215 ponds, 144 showed GCHD-positive responses to RT-PCR assay. In addition, survey results revealed that inferior environmental conditions occurred in most ponds with an incidence of GCHD; such conditions included a thick mud layer; no cleansing and restoration practices (CRPs) before culture; and poor water quality (i.e., high ammonia nitrogen and nitrite concentrations and low transparency). Logistic regression model results suggested that decreased risks were associated with fry vaccination, a safe water source, and deepening of the water level, whereas increased risk factors mainly included no CRPs, excessive rearing density, disease history, and inferior water quality. Presently, control efforts are restricted to immunization of Grass Carp as the best management option for farms. Deepening the water levels and improving water sources can also effectively reduce the incidence of GCHD by diluting the pond rearing densities. PMID:24341768

  14. [Cerebral hemorrhage].

    PubMed

    Nakase, Hiroyuki; Motoyama, Yasushi; Yamada, Shuichi

    2016-04-01

    Intracerebral hemorrhage (ICH) remains a serious condition for which early aggressive care is warranted. Japanese evidence-based stroke guidelines were published in 2015 to present the current and comprehensive recommendations for the diagnosis and treatment of stroke. In the spontaneous ICH, topics focused on prevention, management in the acute and chronic stage, complications, management of coagulopathy and blood pressure, prevention and control of secondary brain injury and intracranial pressure, the role of surgery, and other pathologies of ICH. The management of ICH in pregnancy and the puerperium was newly added. These guidelines provide a framework for goal-directed treatment of the patient with ICH. PMID:27333758

  15. Management of Intraventricular Hemorrhage

    PubMed Central

    Hinson, Holly E.; Ziai, Wendy C.

    2011-01-01

    Brain hemorrhage is the most fatal form of stroke and has the highest morbidity of any stroke subtype. Intraventricular extension of hemorrhage (IVH) is a particularly poor prognostic sign, with expected mortality between 50% and 80%. IVH is a significant and independent contributor to morbidity and mortality, yet therapy directed at ameliorating intraventricular clot has been limited. Conventional therapy centers on managing hypertension and intracranial pressure while correcting coagulopathy and avoiding complications such as rebleeding and hydrocephalus. Surgical therapy alone has not changed the natural history of the disease significantly. However, fibrinolysis in combination with extraventricular drainage shows promise as a technique to reduce intraventricular clot volume and to manage the concomitant complications of IVH. PMID:20425231

  16. Codon optimization of the rabbit hemorrhagic disease virus (RHDV) capsid gene leads to increased gene expression in Spodoptera frugiperda 9 (Sf9) cells

    PubMed Central

    Gao, Jingpeng; Meng, Chunchun; Chen, Zongyan; Li, Chuanfeng

    2013-01-01

    Rabbit hemorrhagic disease (RHD) is contagious and highly lethal. Commercial vaccines against RHD are produced from the livers of experimentally infected rabbits. Although several groups have reported that recombinant subunit vaccines against rabbit hemorrhagic disease virus (RHDV) are promising, application of the vaccines has been restricted due to high production costs or low yield. In the present study, we performed codon optimization of the capsid gene to increase the number of preference codons and eliminate rare codons in Spodoptera frugiperda 9 (Sf9) cells. The capsid gene was then subcloned into the pFastBac plasmid, and the recombinant baculoviruses were identified with a plaque assay. As expected, expression of the optimized capsid protein was markedly increased in the Sf9 cells, and the recombinant capsid proteins self-assembled into virus-like particles (VLPs) that were released into the cell supernatant. Rabbits inoculated with the supernatant and the purified VLPs were protected against RHDV challenge. A rapid, specific antibody response against RHDV was detected by an ELISA in all of the experimental groups. In conclusion, this strategy of producing a recombinant subunit vaccine antigen can be used to develop a low-cost, insect cell-derived recombinant subunit vaccine against RHDV. PMID:23820215

  17. Bovine adenovirus-3 as a vaccine delivery vehicle.

    PubMed

    Ayalew, Lisanework E; Kumar, Pankaj; Gaba, Amit; Makadiya, Niraj; Tikoo, Suresh K

    2015-01-15

    The use of vaccines is an effective and relatively inexpensive means of controlling infectious diseases, which cause heavy economic losses to the livestock industry through animal loss, decreased productivity, treatment expenses and decreased carcass quality. However, some vaccines produced by conventional means are imperfect in many respects including virulence, safety and efficacy. Moreover, there are no vaccines for some animal diseases. Although genetic engineering has provided new ways of producing effective vaccines, the cost of production for veterinary use is a critical criterion for selecting the method of production and delivery of vaccines. The cost effective production and intrinsic ability to enter cells has made adenovirus vectors a highly efficient tool for delivery of vaccine antigens. Moreover, adenoviruses induce both humoral and cellular immune responses to expressed vaccine antigens. Since nonhuman adenoviruses are species specific, the development of animal specific adenoviruses as vaccine delivery vectors is being evaluated. This review summarizes the work related to the development of bovine adenovirus-3 as a vaccine delivery vehicle in animals, particularly cattle. PMID:25498212

  18. 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

  19. Macrovascular Lesions Underlying Spontaneous Intracerebral Hemorrhage.

    PubMed

    Yeung, Jacky; Cord, Branden J; O'Rourke, Timothy K; Maina, Renee M; Sommaruga, Samuel; Matouk, Charles C

    2016-06-01

    Spontaneous intracerebral hemorrhage (ICH) is a morbid disease with a high case fatality rate. Prognosis, rehemorrhage rates, and acute, clinical decision making are greatly affected by the underlying etiology of hemorrhage. This review focuses on the evaluation, diagnosis, and management of structural, macrovascular lesions presenting with ICH, including ruptured aneurysms, brain arteriovenous malformations, cranial dural arteriovenous fistulas, and cerebral cavernous malformations. PMID:27214699

  20. Multi-event capture-recapture modeling of host-pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns.

    PubMed

    Santoro, Simone; Pacios, Isa; Moreno, Sacramento; Bertó-Moran, Alejandro; Rouco, Carlos

    2014-01-01

    Host-pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture-recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host-pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

  1. Multi-event capture–recapture modeling of host–pathogen dynamics among European rabbit populations exposed to myxoma and Rabbit Hemorrhagic Disease Viruses: common and heterogeneous patterns

    PubMed Central

    2014-01-01

    Host–pathogen epidemiological processes are often unclear due both to their complexity and over-simplistic approaches used to quantify them. We applied a multi-event capture–recapture procedure on two years of data from three rabbit populations to test hypotheses about the effects on survival of, and the dynamics of host immunity to, both myxoma virus and Rabbit Hemorrhagic Disease Virus (MV and RHDV). Although the populations shared the same climatic and management conditions, MV and RHDV dynamics varied greatly among them; MV and RHDV seroprevalences were positively related to density in one population, but RHDV seroprevalence was negatively related to density in another. In addition, (i) juvenile survival was most often negatively related to seropositivity, (ii) RHDV seropositives never had considerably higher survival, and (iii) seroconversion to seropositivity was more likely than the reverse. We suggest seropositivity affects survival depending on trade-offs among antibody protection, immunosuppression and virus lethality. Negative effects of seropositivity might be greater on juveniles due to their immature immune system. Also, while RHDV directly affects survival through the hemorrhagic syndrome, MV lack of direct lethal effects means that interactions influencing survival are likely to be more complex. Multi-event modeling allowed us to quantify patterns of host–pathogen dynamics otherwise difficult to discern. Such an approach offers a promising tool to shed light on causative mechanisms. PMID:24708296

  2. Hemorrhagic Fevers

    MedlinePlus

    ... by four families of viruses. These include the Ebola and Marburg, Lassa fever, and yellow fever viruses. ... Some VHFs cause mild disease, but some, like Ebola or Marburg, cause severe disease and death. VHFs ...

  3. Subarachnoid hemorrhage due to nonbranching aneurysm of the middle cerebral artery in a young adult with a history of Kawasaki disease

    PubMed Central

    Ishida, Atsushi; Matsuo, Seigo; Kawamura, Shunji; Nishikawa, Toshio

    2014-01-01

    Background: The incidence of subarachnoid hemorrhage (SAH) in young adults is relatively rare. Kawasaki disease is a systemic vasculopathy that is known to cause coronary artery aneurysms; however, its effect on cerebral arteries remains largely unclear. Case Description: We report the case of a 20-year-old male with a history of Kawasaki disease who presented with SAH caused by the rupture of a nonbranching middle cerebral artery aneurysm. This is the third report of SAH associated with Kawasaki disease. Preoperative echocardiography of the patient rejected the presence of bacterial endocarditis and other heart abnormalities. An emergency craniotomy and clip occlusion of the aneurysm was successfully performed without obstructing the parent artery. Two weeks later, the patient was discharged without any apparent neurological deficit. We also performed a circumstantial pathological study on specimens obtained from the aneurysm wall. Our histological findings suggest that the elastic lamina and tunica intima were completely destroyed during the acute vasculitis phase of Kawasaki disease, which possibly led to the aneurysmal formation. Conclusions: Lack of active inflammatory changes and atherosclerotic lesions may explain the chronic feature of Kawasaki disease, not a typical aneurysmal formation. PMID:24575320

  4. Climate and climate change and infectious disease risk in Thailand: A spatial study of dengue hemorrhagic fever using GIS and remotely-sensed imagery

    NASA Astrophysics Data System (ADS)

    Kuzera, Kristopher

    The scientific community has widely accepted that climate plays a key role in the sustainability and transmission of many infectious diseases. Global climate change can potentially trigger the spread of disease into new regions and increase the intensity of disease in regions where it is endemic. This study explores the association between monthly conditions of climate change to changes in disease risk, emphasizing the potential spread of dengue fever due to climate change in Thailand. This study also develops techniques new to GIS and remote sensing that generate surfaces of daily minimum temperature toward identifying areas at greater transmission risk. Dengue fever expansion due to global warming is a serious concern for Thailand where warming temperatures may increase the size of the habitat of the disease-spreading vector, Aedes aegypti, particularly during cooler months when transmission is limited by environmental conditions. In this study, first, the association between past dengue hemorrhagic fever (DHF) and climate in Thailand is determined. Second, evidence of recent climate change is related to changes in DHF rates. Third, daily minimum temperature is derived from remote sensing toward identifying the spatial and temporal limitations of potential transmission risk. The results indicate that minimum temperature has recently experienced a rapid increase, particularly in the winter months when transmission is low. This is associated with a recent rise in winter DHF cases. As increasing minimum temperatures in these regions are anticipated to continue, we can expect dengue transmission rates to also increase throughout the year.

  5. Functional prediction of hypothetical proteins in human adenoviruses.

    PubMed

    Dorden, Shane; Mahadevan, Padmanabhan

    2015-01-01

    Assigning functional information to hypothetical proteins in virus genomes is crucial for gaining insight into their proteomes. Human adenoviruses are medium sized viruses that cause a range of diseases. Their genomes possess proteins with uncharacterized function known as hypothetical proteins. Using a wide range of protein function prediction servers, functional information was obtained about these hypothetical proteins. A comparison of functional information obtained from these servers revealed that some of them produced functional information, while others provided little functional information about these human adenovirus hypothetical proteins. The PFP, ESG, PSIPRED, 3d2GO, and ProtFun servers produced the most functional information regarding these hypothetical proteins. PMID:26664031

  6. Distribution and Molecular Characterization of Human Adenovirus and Epstein-Barr Virus Infections in Tonsillar Lymphocytes Isolated from Patients Diagnosed with Tonsillar Diseases

    PubMed Central

    Assadian, Farzaneh; Sandström, Karl; Bondeson, Kåre; Laurell, Göran; Lidian, Adnan; Svensson, Catharina; Akusjärvi, Göran

    2016-01-01

    Surgically removed palatine tonsils provide a conveniently accessible source of T and B lymphocytes to study the interplay between foreign pathogens and the host immune system. In this study we have characterised the distribution of human adenovirus (HAdV), Epstein-Barr virus (EBV) and human cytomegalovirus (HCMV) in purified tonsillar T and B cell-enriched fractions isolated from three patient age groups diagnosed with tonsillar hypertrophy and chronic/recurrent tonsillitis. HAdV DNA was detected in 93 out of 111 patients (84%), while EBV DNA was detected in 58 patients (52%). The most abundant adenovirus type was HAdV-5 (68%). None of the patients were positive for HCMV. Furthermore, 43 patients (39%) showed a co-infection of HAdV and EBV. The majority of young patients diagnosed with tonsillar hypertrophy were positive for HAdV, whereas all adult patients diagnosed with chronic/recurrent tonsillitis were positive for either HAdV or EBV. Most of the tonsils from patients diagnosed with either tonsillar hypertrophy or chronic/recurrent tonsillitis showed a higher HAdV DNA copy number in T compared to B cell-enriched fraction. Interestingly, in the majority of the tonsils from patients with chronic/recurrent tonsillitis HAdV DNA was detected in T cells only, whereas hypertrophic tonsils demonstrated HAdV DNA in both T and B cell-enriched fractions. In contrast, the majority of EBV positive tonsils revealed a preference for EBV DNA accumulation in the B cell-enriched fraction compared to T cell fraction irrespective of the patients' age. PMID:27136093

  7. Human adenovirus type 8 epidemic keratoconjunctivitis with large corneal epithelial full-layer detachment: an endemic outbreak with uncommon manifestations

    PubMed Central

    Lee, Yueh-Chang; Chen, Nancy; Huang, I-Tsong; Yang, Hui-Hua; Huang, Chin-Te; Chen, Li-Kuang; Sheu, Min-Muh

    2015-01-01

    Epidemic viral conjunctivitis is a highly contagious disease that is encountered year-round. The causative agents are mainly adenoviruses and enteroviruses. It occurs most commonly upon infection with subgroup D adenoviruses of types 8, 19, or 37. For common corneal involvement of human adenovirus type 8 epidemic keratoconjunctivitis, full-layer epithelial detachment is rarely seen. Herein, we report three cases of epidemic keratoconjunctivitis during an outbreak which manifested as large corneal epithelial full-layer detachment within a few days. The lesions healed without severe sequelae under proper treatment. The unique manifestation of this outbreak may indicate the evolution of human adenovirus type 8. PMID:26060391

  8. Epizootic Hemorrhagic Disease Outbreak in a Captive Facility Housing White-tailed Deer (Odocoileus Virginianus), Bison (Bison Bison), Elk (Cervus Elaphus), Cattle (Bos Taurus) and Goats (Capra Hircus) in Colorado

    Technology Transfer Automated Retrieval System (TEKTRAN)

    A captive wildlife research facility in Fort Collins, Colorado experienced mortality in white-tailed deer (Odocoileus virginianus) due to epizootic hemorrhagic disease virus (EHDV) infection in late summer and early fall of 2007. RNA from EHDV was amplified by RT-PCR from the spleen and lung tissues...

  9. Drought, epidemic disease, and the fall of classic period cultures in Mesoamerica (AD 750-950). Hemorrhagic fevers as a cause of massive population loss.

    PubMed

    Acuna-Soto, Rodolfo; Stahle, David W; Therrell, Matthew D; Gomez Chavez, Sergio; Cleaveland, Malcolm K

    2005-01-01

    The classical period in Mexico (AD 250-750) was an era of splendor. The city of Teotihuacan was one of the largest and most sophisticated human conglomerates of the pre-industrial world. The Mayan civilization in southeastern Mexico and the Yucatan peninsula reached an impressive degree of development at the same time. This time of prosperity came to an end during the Terminal Classic Period (AD 750-950) a time of massive population loss throughout Mesoamerica. A second episode of massive depopulation in the same area was experienced during the sixteenth century when, in less than one century, between 80% and 90% of the entire indigenous population was lost. The 16th century depopulation of Mexico constitutes one of the worst demographic catastrophes in human history. Although newly imported European and African diseases caused high mortality among the native population, the major 16th century population losses were caused by a series of epidemics of a hemorrhagic fever called Cocoliztli, a highly lethal disease unknown to both Aztec and European physicians during the colonial era. The cocoliztli epidemics occurred during the 16th century megadrought, when severe drought extended at times from central Mexico to the boreal forest of Canada, and from the Pacific to the Atlantic coast. The collapse of the cultures of the Classic Period seems also to have occurred during a time of severe drought. Tree ring and lake sediment records indicate that some of the most severe and prolonged droughts to impact North America-Mesoamerica in the past 1000-4000 years occurred between AD 650 and 1000, particularly during the 8th and 9th centuries, a period of time that coincides with the Terminal Classic Period. Based on the similarities of the climatic (severe drought) and demographic (massive population loss) events in Mesoamerica during the sixteenth century, we propose that drought-associated epidemics of hemorrhagic fever may have contributed to the massive population loss

  10. Protective Efficacy in Sheep of Adenovirus-Vectored Vaccines against Bluetongue Virus Is Associated with Specific T Cell Responses

    PubMed Central

    Martín, Verónica; Pascual, Elena; Avia, Miguel; Peña, Lourdes; Valcárcel, Félix; Sevilla, Noemí

    2015-01-01

    Bluetongue virus (BTV) is an economically important Orbivirus of the Reoviridae family that causes a hemorrhagic disease in ruminants. Its control has been achieved by inactivated-vaccines that have proven to protect against homologous BTV challenge although unable to induce long-term immunity. Therefore, a more efficient control strategy needs to be developed. Recombinant adenovirus vectors are lead vaccine candidates for protection of several diseases, mainly because of their potency to induce potent T cell immunity. Here we report the induction of humoral and T-cell mediated responses able to protect animals against BTV challenge by recombinant replication-defective human adenovirus serotype 5 (Ad5) expressing either VP7, VP2 or NS3 BTV proteins. First we used the IFNAR(-/-) mouse model system to establish a proof of principle, and afterwards we assayed the protective efficacy in sheep, the natural host of BTV. Mice were completely protected against BTV challenge, developing humoral and BTV-specific CD8+- and CD4+-T cell responses by vaccination with the different rAd5. Sheep vaccinated with Ad5-BTV-VP2 and Ad5-BTV-VP7 or only with Ad5-BTV-VP7 and challenged with BTV showed mild disease symptoms and reduced viremia. This partial protection was achieved in the absence of neutralizing antibodies but strong BTV-specific CD8+ T cell responses in those sheep vaccinated with Ad5-BTV-VP7. These data indicate that rAd5 is a suitable vaccine vector to induce T cell immunity during BTV vaccination and provide new data regarding the relevance of T cell responses in protection during BTV infection. PMID:26619062

  11. Robust Protection against Highly Virulent Foot-and-Mouth Disease Virus in Swine by Combination Treatment with Recombinant Adenoviruses Expressing Porcine Alpha and Gamma Interferons and Multiple Small Interfering RNAs

    PubMed Central

    Park, Jong-Hyeon; Lee, Kwang-Nyeong; Kim, Se-Kyung; You, Su-Hwa; Kim, Taeseong; Tark, Dongseob; Lee, Hyang-Sim; Seo, Min-Goo; Kim, Byounghan

    2015-01-01

    ABSTRACT Because the currently available vaccines against foot-and-mouth disease (FMD) provide no protection until 4 to 7 days postvaccination, the only alternative method to halt the spread of the FMD virus (FMDV) during outbreaks is the application of antiviral agents. Combination treatment strategies have been used to enhance the efficacy of antiviral agents, and such strategies may be advantageous in overcoming viral mechanisms of resistance to antiviral treatments. We have developed recombinant adenoviruses (Ads) for the simultaneous expression of porcine alpha and gamma interferons (Ad-porcine IFN-αγ) as well as 3 small interfering RNAs (Ad-3siRNA) targeting FMDV mRNAs encoding nonstructural proteins. The antiviral effects of Ad-porcine IFN-αγ and Ad-3siRNA expression were tested in combination in porcine cells, suckling mice, and swine. We observed enhanced antiviral effects in porcine cells and mice as well as robust protection against the highly pathogenic strain O/Andong/SKR/2010 and increased expression of cytokines in swine following combination treatment. In addition, we showed that combination treatment was effective against all serotypes of FMDV. Therefore, we suggest that the combined treatment with Ad-porcine IFN-αγ and Ad-3siRNA may offer fast-acting antiviral protection and be used with a vaccine during the period that the vaccine does not provide protection against FMD. IMPORTANCE The use of current foot-and-mouth disease (FMD) vaccines to induce rapid protection provides limited effectiveness because the protection does not become effective until a minimum of 4 days after vaccination. Therefore, during outbreaks antiviral agents remain the only available treatment to confer rapid protection and reduce the spread of foot-and-mouth disease virus (FMDV) in livestock until vaccine-induced protective immunity can become effective. Interferons (IFNs) and small interfering RNAs (siRNAs) have been reported to be effective antiviral agents against

  12. Canine adenovirus based rabies vaccines.

    PubMed

    Tordo, N; Foumier, A; Jallet, C; Szelechowski, M; Klonjkowski, B; Eloit, M

    2008-01-01

    Adenovirus based vectors are very attractive candidates for vaccination purposes as they induce in mammalian hosts potent humoral, mucosal and cellular immune responses to antigens encoded by the inserted genes. We have generated E1-deleted and replication-competent recombinant canine type-2 adenoviruses expressing the rabies virus glycoprotein (G). The effectiveness of both vectors to express a native G protein has been characterized in vitro in permissive cell lines. We compared the humoral and cellular immune responses induced in mice by intramuscular injection of the recombinant canine adenovirus vectors with those induced by a human (Ad5) E1-deleted virus expressing the same rabies G protein. Humoral responses specific to the adenoviruses or the rabies glycoprotein antigens were studied. The influence of the mouse strain was observed using replication-competent canine adenovirus. A high level of rabies neutralizing antibody was observed upon i.m. inoculation, and 100% of mice survived lethal challenge. These results are very promising in the perspective of oral vaccine for dog rabies control. PMID:18634509

  13. Molecular characterization of adenovirus circulating in Central and South America during the 2006–2008 period

    PubMed Central

    García, Josefina; Sovero, Merly; Laguna‐Torres, Victor Alberto; Gomez, Jorge; Chicaiza, Wilson; Barrantes, Melvin; Sanchez, Felix; Jimenez, Mirna; Comach, Guillermo; De Rivera, Ivette L.; Agudo, Roberto; Arango, Ana E.; Barboza, Alma; Aguayo, Nicolas; Kochel, Tadeusz J.

    2009-01-01

    Background  Human Adenoviruses are recognized pathogens, causing a broad spectrum of diseases. Serotype identification is critical for epidemiological surveillance, detection of new strains and understanding of HAdvs pathogenesis. Little data is available about HAdvs subtypes in Latin America. Methods  In this study, we have molecularly characterized 213 adenoviruses collected from ILI presenting patients, during 2006‐08, in Central and South America. Results  Our results indicate that 161(76%) adenoviruses belong to subgroup C, 45 (21%) to subgroup B and 7 (3%) to subtype E4. PMID:19903214

  14. Complex adenovirus-vectored vaccine protects guinea pigs from three strains of Marburg virus challenges

    SciTech Connect

    Wang Danher; Hevey, Michael; Juompan, Laure Y.; Trubey, Charles M.; Raja, Nicholas U.; Deitz, Stephen B.; Woraratanadharm, Jan; Luo Min; Yu Hong; Swain, Benjamin M.; Moore, Kevin M.; Dong, John Y. . E-mail: dongj@genphar.com

    2006-09-30

    The Marburg virus (MARV), an African filovirus closely related to the Ebola virus, causes a deadly hemorrhagic fever in humans, with up to 90% mortality. Currently, treatment of disease is only supportive, and no vaccines are available to prevent spread of MARV infections. In order to address this need, we have developed and characterized a novel recombinant vaccine that utilizes a single complex adenovirus-vectored vaccine (cAdVax) to overexpress a MARV glycoprotein (GP) fusion protein derived from the Musoke and Ci67 strains of MARV. Vaccination with the cAdVaxM(fus) vaccine led to efficient production of MARV-specific antibodies in both mice and guinea pigs. Significantly, guinea pigs vaccinated with at least 5 x 10{sup 7} pfu of cAdVaxM(fus) vaccine were 100% protected against lethal challenges by the Musoke, Ci67 and Ravn strains of MARV, making it a vaccine with trivalent protective efficacy. Therefore, the cAdVaxM(fus) vaccine serves as a promising vaccine candidate to prevent and contain multi-strain infections by MARV.

  15. [Hemorrhagic disorders in pregnancy].

    PubMed

    Ludwig, H

    1999-10-01

    When bleeding disorders coincide with pregnancy, they might be congenital or acquired diseases, if not arising as a more acute complication of the pregnancy itself. The paper gives a review of the most common bleeding disorders out of internal medical constellations. History taking is the most effective way to open the diagnostic approach. If childbearing is desired the couple in question should be counselled accordingly in collaboration with a hematologist. Some conditions might be unfavourable, e.g. hemophila in male offspring, others might be serious but manageable, as in v. Willebrand-Disease or autoimmunologic thrombocytopenic purpura. Prenatal invasive diagnostics with fetal blood sampling at an early stage of pregnancy may reduce the hazards for the baby insofar, as it allows the more precise estimation of fetal risks at birth. Cesarean section will not in all cases be the way of choice (e.g. in v. Willebrand-Disease), in others it might be the better way to deliver a fetus at risk in order to avoid intracranial hemorrhage (in severe cases of ITP). Always both, mother and fetus, are at risk, but almost in any cases in different shades and grades of severeness. There is rarely a firm correlation of the maternal and the fetal hemostatic parameters in cases of connatal or acquired hemorrhagic disorders. Pregnancy itself leads to a certain compensation of defects in clotting factors, since the synthesis of factors increase or they are circulating more in activated form. Pregnancy is a state of a silently ongoing intravascular coagulation at least in the uteroplacental circulation. From there it is linked with the general circulation of the maternal organism. When immunologic etiologies in thrombocytopenias play a role, there will always be the incalculable rate of placental transfer of antiplatelet-antibodies to the fetus. The entire field requires knowledge, counseling, collaboration and foresight. PMID:10549234

  16. Adenoviruses in the immunocompromised host.

    PubMed Central

    Hierholzer, J C

    1992-01-01

    Adenoviruses are among the many pathogens and opportunistic agents that cause serious infection in the congenitally immunocompromised, in patients undergoing immunosuppressive treatment for organ and tissue transplants and for cancers, and in human immunodeficiency virus-infected patients. Adenovirus infections in these patients tend to become disseminated and severe, and the serotypes involved are clustered according to the age of the patient and the nature of the immunosuppression. Over 300 adenovirus infections in immunocompromised patients, with an overall case fatality rate of 48%, are reviewed in this paper. Children with severe combined immunodeficiency syndrome and other primary immunodeficiencies are exposed to the serotypes of subgroups B and C that commonly infect young children, and thus their infections are due to types 1 to 7 and 31 of subgenus A. Children with bone marrow and liver transplants often have lung and liver adenovirus infections that are due to an expanded set of subgenus A, B, C, and E serotypes. Adults with kidney transplants have viruses of subgenus B, mostly types 11, 34, and 35, which cause cystitis. This review indicates that 11% of transplant recipients become infected with adenoviruses, with case fatality rates from 60% for bone marrow transplant patients to 18% for renal transplant patients. Patients with AIDS become infected with a diversity of serotypes of all subgenera because their adult age and life-style expose them to many adenoviruses, possibly resulting in antigenically intermediate strains that are not found elsewhere. Interestingly, isolates from the urine of AIDS patients are generally of subgenus B and comprise types 11, 21, 34, 35, and intermediate strains of these types, whereas isolates from stool are of subgenus D and comprise many rare, new, and intermediate strains that are untypeable for practical purposes. It has been estimated that adenoviruses cause active infection in 12% of AIDS patients and that 45% of

  17. Comparative Genome Analysis of Four Elephant Endotheliotropic Herpesviruses, EEHV3, EEHV4, EEHV5, and EEHV6, from Cases of Hemorrhagic Disease or Viremia

    PubMed Central

    Zong, Jian-Chao; Latimer, Erin M.; Long, Simon Y.; Richman, Laura K.; Heaggans, Sarah Y.

    2014-01-01

    ABSTRACT The genomes of three types of novel endotheliotropic herpesviruses (elephant endotheliotropic herpesvirus 1A [EEHV1A], EEHV1B, and EEHV2) associated with lethal hemorrhagic disease in Asian elephants have been previously well characterized and assigned to a new Proboscivirus genus. Here we have generated 112 kb of DNA sequence data from segments of four more types of EEHV by direct targeted PCR from blood samples or necropsy tissue samples from six viremic elephants. Comparative phylogenetic analysis of nearly 30 protein-encoding genes of EEHV5 and EEHV6 show that they diverge uniformly by nearly 20% from their closest relatives, EEHV2 and EEHV1A, respectively, and are likely to have similar overall gene content and genome organization. In contrast, seven EEHV3 and EEHV4 genes analyzed differ from those of all other EEHVs by 37% and have a G+C content of 63% compared to just 42% for the others. Three strains of EEHV5 analyzed clustered into two partially chimeric subgroups EEHV5A and EEHV5B that diverge by 19% within three small noncontiguous segments totaling 6.2 kb. We conclude that all six EEHV types should be designated as independent species within a proposed new fourth Deltaherpesvirinae subfamily of mammalian herpesviruses. These virus types likely initially diverged close to 100 million years ago when the ancestors of modern elephants split from all other placental mammals and then evolved into two major branches with high- or low-G+C content about 35 million years ago. Later additional branching events subsequently generated three paired sister taxon lineages of which EEHV1 plus EEHV6, EEHV5 plus EEHV2, and EEHV4 plus EEHV3 may represent Asian and African elephant versions, respectively. IMPORTANCE One of the factors threatening the long-term survival of endangered Asian elephants in both wild range countries and in captive breeding populations in zoos is a highly lethal hemorrhagic herpesvirus disease that has killed at least 70 young Asian

  18. Mechanism by which calcium phosphate coprecipitation enhances adenovirus-mediated gene transfer.

    PubMed

    Walters, R; Welsh, M

    1999-11-01

    Delivery of a normal copy of CFTR cDNA to airway epithelia may provide a novel treatment for cystic fibrosis lung disease. Unfortunately, current vectors are inefficient because of limited binding to the apical surface of airway epithelia. We recently reported that incorporation of adenovirus in a calcium phosphate coprecipitate (Ad:CaPi) improves adenovirus-mediated gene transfer to airway epithelia in vitro and in vivo. To understand better how coprecipitation improves gene transfer, we tested the hypothesis that incorporation in a CaPi coprecipitate increases the binding of adenovirus to the apical surface of differentiated human airway epithelia. When a Cy3-labelled adenovirus was delivered in a coprecipitate, binding increased 54-fold as compared with adenovirus alone. Moreover, infection by Ad:CaPi was independent of fiber knob-CAR and penton base-integrin interactions. After binding to the cell surface, the virus must enter the cell in order to infect. We hypothesized that Ad:CaPi may stimulate fluid phase endocytosis, thereby facilitating entry. However, we found that neither adenovirus nor Ad:CaPi coprecipitates altered fluid phase endocytosis. Nevertheless, Ad:CaPi preferentially infected cells showing endocytosis. Thus, CaPi coprecipitation improves adenovirus-mediated gene transfer by coating the epithelial surface with a layer of virus which enters cells during the normal process of endocytosis. PMID:10602380

  19. COL4A1 Mutation in Preterm Intraventricular Hemorrhage

    PubMed Central

    Bilguvar, Kaya; DiLuna, Michael L.; Bizzarro, Matthew J.; Bayri, Yasar; Schneider, Karen C.; Lifton, Richard P.; Gunel, Murat; Ment, Laura R.

    2010-01-01

    Intraventricular hemorrhage is a common complication of preterm infants. Mutations in the type IV procollagen gene, COL4A1, are associated with cerebral small vessel disease with hemorrhage in adults and fetuses. We report a rare variant in COL4A1 associated with intraventricular hemorrhage in dizygotic preterm twins. These results expand the spectrum of diseases attributable to mutations in type IV procollagens. PMID:19840616

  20. Isolation and Epidemiology of Falcon Adenovirus

    PubMed Central

    Oaks, J. Lindsay; Schrenzel, Mark; Rideout, Bruce; Sandfort, Cal

    2005-01-01

    An adenovirus was detected by electron microscopy in tissues from falcons that died during an outbreak of inclusion body hepatitis and enteritis that affected neonatal Northern aplomado (Falco femoralis septentrionalis) and peregrine (Falco peregrinus anatum) falcons. Molecular characterization has identified the falcon virus as a new member of the aviadenovirus group (M. Schrenzel, J. L. Oaks, D. Rotstein, G. Maalouf, E. Snook, C. Sandfort, and B. Rideout, J. Clin. Microbiol. 43:3402-3413, 2005). In this study, the virus was successfully isolated and propagated in peregrine falcon embryo fibroblasts, in which it caused visible and reproducible cytopathology. Testing for serum neutralizing antibodies found that infection with this virus was limited almost exclusively to falcons. Serology also found that wild and captive peregrine falcons had high seropositivity rates of 80% and 100%, respectively, although clinical disease was rarely reported in this species. These data implicate peregrine falcons as the natural host and primary reservoir for the virus. Other species of North American falcons, including aplomado falcons, had lower seropositivity rates of 43 to 57%. Falcon species of tropical and/or island origin were uniformly seronegative, although deaths among adults of these species have been described, suggesting they are highly susceptible. Chickens and quail were uniformly seronegative and not susceptible to infection, indicating that fowl were not the source of infection. Based on the information from this study, the primary control of falcon adenovirus infections should be based on segregation of carrier and susceptible falcon species. PMID:16000467

  1. Clinical aspects of Marburg hemorrhagic fever

    PubMed Central

    Mehedi, Masfique; Groseth, Allison; Feldmann, Heinz; Ebihara, Hideki

    2011-01-01

    Marburg virus belongs to the genus Marburgvirus in the family Filoviridae and causes a severe hemorrhagic fever, known as Marburg hemorrhagic fever (MHF), in both humans and nonhuman primates. Similar to the more widely known Ebola hemorrhagic fever, MHF is characterized by systemic viral replication, immunosuppression and abnormal inflammatory responses. These pathological features of the disease contribute to a number of systemic dysfunctions including hemorrhages, edema, coagulation abnormalities and, ultimately, multiorgan failure and shock, often resulting in death. A detailed understanding of the pathological processes that lead to this devastating disease remains elusive, a fact that contributes to the lack of licensed vaccines or effective therapeutics. This article will review the clinical aspects of MHF and discuss the pathogenesis and possible options for diagnosis, treatment and prevention. PMID:22046196

  2. Replication of type 5 adenovirus promotes middle ear infection by Streptococcus pneumoniae in the chinchilla model of otitis media.

    PubMed

    Murrah, Kyle A; Turner, Roberta L; Pang, Bing; Perez, Antonia C; Reimche, Jennifer L; King, Lauren B; Wren, John; Gandhi, Uma; Swords, W Edward; Ornelles, David A

    2015-03-01

    Adenoviral infection is a major risk factor for otitis media. We hypothesized that adenovirus promotes bacterial ascension into the middle ear through the disruption of normal function in the Eustachian tubes due to inflammation-induced changes. An intranasal infection model of the chinchilla was used to test the ability of type 5 adenovirus to promote middle ear infection by Streptococcus pneumoniae. The hyperinflammatory adenovirus mutant dl327 and the nonreplicating adenovirus mutant H5wt300ΔpTP were used to test the role of inflammation and viral replication, respectively, in promotion of pneumococcal middle ear infection. Precedent infection with adenovirus resulted in a significantly greater incidence of middle ear disease by S. pneumoniae as compared to nonadenovirus infected animals. Infection with the adenovirus mutant dl327 induced a comparable degree of bacterial ascension into the middle ear as did infection with the wild-type virus. By contrast, infection with the nonreplicating adenovirus mutant H5wt300ΔpTP resulted in less extensive middle ear infection compared to the wild-type adenovirus. We conclude that viral replication is necessary for adenoviral-induced pneumococcal middle ear disease. PMID:25251686

  3. In vitro transcription of adenovirus.

    PubMed Central

    Fire, A; Baker, C C; Manley, J L; Ziff, E B; Sharp, P A

    1981-01-01

    A series of recombinants of adenovirus DNA fragments and pBR322 was used to test the transcriptional activity of the nine known adenovirus promoters in a cell-free extract. Specific initiation was seen at all five early promoters as well as at the major late promotor and at the intermediate promoter for polypeptide IX. The system failed to recognize the two other adenovirus promoters, which were prominent in vivo only at intermediate and late stages in infection. Microheterogeneity of 5' termini at several adenovirus promoters, previously shown in vivo, was reproduced in the in vitro reaction and indeed appeared to result from heterogeneous initiation rather than 5' processing. To test for the presence of soluble factors involved in regulation of nRNA synthesis, the activity of extracts prepared from early and late stages of infection was compared on an assortment of viral promoter sites. Although mock and early extracts showed identical transcription patterns, extracts prepared from late stages gave 5- to 10-fold relative enhancement of the late and polypeptide IX promoters as compared with early promoters. Images PMID:7321101

  4. Mechanism of adenovirus-mediated endosome lysis: role of the intact adenovirus capsid structure.

    PubMed

    Seth, P

    1994-12-15

    Adenoviruses have been previously shown to enhance the delivery of many ligands including proteins and plasmid DNAs to the cells. The key biochemical step during this process is the ability of adenovirus to disrupt (lyse) the endosome membrane releasing the co-internalized virus and the other ligands into the cytosol (Seth et al, 1986, In: Adenovirus attachment and entry into cells, pp 191-195, American Society for Microbiology, Washington, D.C.). To understand the role of the adenovirus proteins involved in the endosome lysis, it is further shown here that empty capsids of adenovirus also possess this membrane vesicle lytic activity; though the activity is about 5-times lower than the adenovirus. Incubation of adenovirus with low concentration of ionic detergent or brief exposure to 45 degrees C destroyed this lytic activity without affecting the adenovirus binding to cell surface receptor, suggesting the lytic activity of adenovirus to be of enzymatic nature. However, exposing adenovirus to conditions that can disrupt adenovirus capsid structure such as heating at 65 degrees C, treating with 0.5% SDS, treating with different proteases, dialyzing against no glycerol buffer, treating with 6 M urea or with 10% pyridine, and sonication destroyed the adenovirus-associated lytic activity. Results suggest the requirement of an intact capsid structure for adenovirus-mediated lysis of the endosome. PMID:7802664

  5. Epidemiological Survey of Crimean-Congo Hemorrhagic Fever (CCHF), a Fatal Infectious Disease in Khuzestan Province, Southwest Iran, During 1999 - 2015

    PubMed Central

    Sharififard, Mona; Alavi, Sayed Mohammad; Salmanzadeh, Shokrollah; Safdari, Farhad; Kamali, Amin

    2016-01-01

    Background Crimean-Congo hemorrhagic fever (CCHF) is an arboviral zoonotic disease transmitted to humans mainly through the bite of blood-sucking Ixodidae ticks and also via contact with the blood and tissues of infected livestock. Objectives This study is a retrospective descriptive survey based on data collected from the health center of Khuzestan province, Iran, during 1999 - 2015. Patients and Methods Patients with symptoms of severe headache, high fever, and bleeding were evaluated. Laboratory tests and serological or molecular assays were used to detect probable and confirmed cases, respectively. The epidemiological parameters of this study were analyzed on the basis of probable cases. Results A total of 42 patients were diagnosed as probable cases, and 17 of these (42.5%) were confirmed serologically. Two peaks of the disease occurred in Khuzestan province, in 2003 and 2010, with seven cases each of those years, leading to the deaths of five and two patients, respectively. Men and women comprised 57.1% and 42.9% of the patients, respectively. Of all probable cases, 64.3% were from urban areas and 35.7% were from rural areas. The age groups of 10 - 19 and 20 - 29 years, with a frequency of 26.2% in each group, were exposed to the most infections. Farmers and housewives were the highest at-risk occupational groups with a frequency of 28.6% and 26%, respectively. Fever, bleeding, and thrombocytopenia were reported in 95% of the patients, and the case-fatality ratio was calculated to be 28.6% (12 of 42 cases). Conclusions Continuous training is necessary to improve the knowledge and awareness of the highest-risk groups with regard to the transmission modes, prevention, symptoms, and treatment of this disease. PMID:27540454

  6. Detection and differentiation of rabbit hemorrhagic disease and European brown hare syndrome viruses by amplification of VP60 genomic sequences from fresh and fixed tissue specimens.

    PubMed Central

    Ros Bascuñana, C; Nowotny, N; Belák, S

    1997-01-01

    Two reverse transcription-PCR (RT-PCR) assays have been developed for the detection and differentiation of rabbit hemorrhagic disease virus (RHDV) and European brown hare syndrome virus (EBHSV), two closely related caliciviruses. In order to select highly specific primers, comparative analysis was performed with a large number of RHDV and EBHSV genomic sequences. Regarding these data, primers were selected from similar regions of the VP60 genes to amplify a fragment of 316 nucleotides from the genome of RHDV and a fragment of 265 nucleotides from the genome of EBHSV. In sensitivity studies, as few as 10 copies of cloned viral genomic fragments were detected in each PCR assay, and no cross amplification was observed between the two viruses. The diagnostic value of the assays was confirmed with clinical material by testing fresh and formalin-fixed, paraffin-embedded liver and spleen specimens from a large number of geographically and temporally distant outbreaks. Thus, the two PCR assays provide highly specific and sensitive, novel means of direct detection of the two caliciviruses. In addition, by detecting the viruses in formalin-fixed, paraffin-embedded tissues (PETs), the RT-PCR assays facilitate retrospective virological and epidemiological studies. For example, the identification of EBHSV in PET specimens collected in the 1970s indicates that this virus appeared in the hare populations several years before the first reports of European brown hare syndrome during the 1980s. PMID:9316895

  7. Self-assembly of virus-like particles of rabbit hemorrhagic disease virus capsid protein expressed in Escherichia coli and their immunogenicity in rabbits.

    PubMed

    Guo, Huimin; Zhu, Jie; Tan, Yonggui; Li, Chuanfeng; Chen, Zongyan; Sun, Shiqi; Liu, Guangqing

    2016-07-01

    In this study, virus-like particles (VLPs) derived from rabbit hemorrhagic disease virus (RHDV) were evaluated for the development of a vaccine against RHDV infection. The VP60 gene was cloned and inserted into a pSMK expression vector containing a small ubiquitin-like modifier (SUMO) tag that can promote the soluble expression of heterologous proteins in Escherichia coli cells. After expression and purification of His-SUMO-VP60 and cleavage of the SUMO tag, we found that the RHDV VP60 protein had self-assembled into VLPs with a similar shape and smaller size compared with authentic RHDV capsid. Next, the antigenicity and immunogenicity of the VLPs were examined. The results showed that RHDV-specific responses were clearly induced in rabbits and that all rabbits in the VLP group survived while those in the negative control group died within 72 h post-infection. These results suggest that VLP-based RHDV could be a promising RHDV vaccine candidate. PMID:27118636

  8. Genetic and Molecular Epidemiological Characterization of a Novel Adenovirus in Antarctic Penguins Collected between 2008 and 2013.

    PubMed

    Lee, Sook-Young; Kim, Jeong-Hoon; Seo, Tae-Kun; No, Jin Sun; Kim, Hankyeom; Kim, Won-Keun; Choi, Han-Gu; Kang, Sung-Ho; Song, Jin-Won

    2016-01-01

    Antarctica is considered a relatively uncontaminated region with regard to the infectious diseases because of its extreme environment, and isolated geography. For the genetic characterization and molecular epidemiology of the newly found penguin adenovirus in Antarctica, entire genome sequencing and annual survey of penguin adenovirus were conducted. The entire genome sequences of penguin adenoviruses were completed for two Chinstrap penguins (Pygoscelis antarctica) and two Gentoo penguins (Pygoscelis papua). The whole genome lengths and G+C content of penguin adenoviruses were found to be 24,630-24,662 bp and 35.5-35.6%, respectively. Notably, the presence of putative sialidase gene was not identified in penguin adenoviruses by Rapid Amplification of cDNA Ends (RACE-PCR) as well as consensus specific PCR. The penguin adenoviruses were demonstrated to be a new species within the genus Siadenovirus, with a distance of 29.9-39.3% (amino acid, 32.1-47.9%) in DNA polymerase gene, and showed the closest relationship with turkey adenovirus 3 (TAdV-3) in phylogenetic analysis. During the 2008-2013 study period, the penguin adenoviruses were annually detected in 22 of 78 penguins (28.2%), and the molecular epidemiological study of the penguin adenovirus indicates a predominant infection in Chinstrap penguin population (12/30, 40%). Interestingly, the genome of penguin adenovirus could be detected in several internal samples, except the lymph node and brain. In conclusion, an analysis of the entire adenoviral genomes from Antarctic penguins was conducted, and the penguin adenoviruses, containing unique genetic character, were identified as a new species within the genus Siadenovirus. Moreover, it was annually detected in Antarctic penguins, suggesting its circulation within the penguin population. PMID:27309961

  9. Genetic and Molecular Epidemiological Characterization of a Novel Adenovirus in Antarctic Penguins Collected between 2008 and 2013

    PubMed Central

    Lee, Sook-Young; Kim, Jeong-Hoon; Seo, Tae-Kun; No, Jin Sun; Kim, Hankyeom; Kim, Won-keun; Choi, Han-Gu; Kang, Sung-Ho; Song, Jin-Won

    2016-01-01

    Antarctica is considered a relatively uncontaminated region with regard to the infectious diseases because of its extreme environment, and isolated geography. For the genetic characterization and molecular epidemiology of the newly found penguin adenovirus in Antarctica, entire genome sequencing and annual survey of penguin adenovirus were conducted. The entire genome sequences of penguin adenoviruses were completed for two Chinstrap penguins (Pygoscelis antarctica) and two Gentoo penguins (Pygoscelis papua). The whole genome lengths and G+C content of penguin adenoviruses were found to be 24,630–24,662 bp and 35.5–35.6%, respectively. Notably, the presence of putative sialidase gene was not identified in penguin adenoviruses by Rapid Amplification of cDNA Ends (RACE-PCR) as well as consensus specific PCR. The penguin adenoviruses were demonstrated to be a new species within the genus Siadenovirus, with a distance of 29.9–39.3% (amino acid, 32.1–47.9%) in DNA polymerase gene, and showed the closest relationship with turkey adenovirus 3 (TAdV-3) in phylogenetic analysis. During the 2008–2013 study period, the penguin adenoviruses were annually detected in 22 of 78 penguins (28.2%), and the molecular epidemiological study of the penguin adenovirus indicates a predominant infection in Chinstrap penguin population (12/30, 40%). Interestingly, the genome of penguin adenovirus could be detected in several internal samples, except the lymph node and brain. In conclusion, an analysis of the entire adenoviral genomes from Antarctic penguins was conducted, and the penguin adenoviruses, containing unique genetic character, were identified as a new species within the genus Siadenovirus. Moreover, it was annually detected in Antarctic penguins, suggesting its circulation within the penguin population. PMID:27309961

  10. Hemorrhagic Stroke in Children

    PubMed Central

    Hillis M.D., Argye E.

    2007-01-01

    Hemorrhagic stroke accounts for approximately half of stroke in childhood. Unlike arterial ischemic stroke, there are no consensus guidelines to assist in the evaluation and treatment of these children. We review the literature on the evaluation, treatment, etiology and neurologic outcome of hemorrhagic stroke in children. Important differences between pediatric and adult hemorrhage are highlighted, as treatment guidelines for adults may not be applicable in all cases. Needed future research and potential therapies are also discussed. PMID:17275656

  11. Pulmonary hemorrhage syndrome associated with an autochthonous case of dengue hemorrhagic fever.

    PubMed

    Setlik, Robert F; Ouellette, Daniel; Morgan, Julia; McAllister, C Kenneth; Dorsey, David; Agan, Brian K; Horvath, Lynn; Zimmerman, Michelle K; Purcell, Bret

    2004-07-01

    Dengue fever is a major public health problem worldwide. Dengue hemorrhagic fever, a much rarer form of the disease, occurs when a person previously infected with dengue is re-infected with a different viral serotype. In recent years the infection rates of dengue and both clinical syndromes have increased along the United States-Mexico border. We present the case of a 61-year-old Laotian female who presented with a 1-week history of fever, altered mental status, oral ulceration, and rash. The patient developed diffuse pulmonary hemorrhage and anemia requiring multiple transfusions. She eventually sustained multi-organ system failure and expired. Both the titer data and serologies were consistent with the diagnosis of dengue hemorrhagic fever. We hypothesize that this syndrome was the result of re-infection occurring within the United States. This case is also unusual in that it is the second reported in the literature of pulmonary hemorrhages associated with dengue hemorrhagic fever. PMID:15301127

  12. Adenovirus-Mediated Efficient Gene Transfer into Cultured Three-Dimensional Organoids

    PubMed Central

    Wang, Ning; Zhang, Hongyu; Zhang, Bing-Qiang; Liu, Wei; Zhang, Zhonglin; Qiao, Min; Zhang, Hongmei; Deng, Fang; Wu, Ningning; Chen, Xian; Wen, Sheng; Zhang, Junhui; Liao, Zhan; Zhang, Qian; Yan, Zhengjian; Yin, Liangjun; Ye, Jixing; Deng, Youlin; Luu, Hue H.; Haydon, Rex C.; Liang, Houjie; He, Tong-Chuan

    2014-01-01

    Three-dimensional organoids have been recently established from various tissue-specific progenitors (such as intestinal stem cells), induced pluripotent stem cells, or embryonic stem cells. These cultured self-sustaining stem cell–based organoids may become valuable systems to study the roles of tissue-specific stem cells in tissue genesis and disease development. It is thus conceivable that effective genetic manipulations in such organoids may allow us to reconstruct disease processes and/or develop novel therapeutics. Recombinant adenoviruses are one of the most commonly used viral vectors for in vitro and in vivo gene deliveries. In this study, we investigate if adenoviruses can be used to effectively deliver transgenes into the cultured “mini-gut” organoids derived from intestinal stem cells. Using adenoviral vectors that express fluorescent proteins, we demonstrate that adenoviruses can effectively deliver transgenes into the cultured 3-D “mini-gut” organoids. The transgene expression can last at least 10 days in the cultured organoids. As a proof-of-principle experiment, we demonstrate that adenovirus-mediated noggin expression effectively support the survival and self-renewal of mini-gut organoids, while adenovirus-mediated expression of BMP4 inhibits the self-sustainability and proliferation of the organoids. Thus, our results strongly suggest that adenovirus vectors can be explored as effective gene delivery vehicles to introduce genetic manipulations in 3-D organoids. PMID:24695466

  13. Adenovirus-mediated efficient gene transfer into cultured three-dimensional organoids.

    PubMed

    Wang, Ning; Zhang, Hongyu; Zhang, Bing-Qiang; Liu, Wei; Zhang, Zhonglin; Qiao, Min; Zhang, Hongmei; Deng, Fang; Wu, Ningning; Chen, Xian; Wen, Sheng; Zhang, Junhui; Liao, Zhan; Zhang, Qian; Yan, Zhengjian; Yin, Liangjun; Ye, Jixing; Deng, Youlin; Luu, Hue H; Haydon, Rex C; Liang, Houjie; He, Tong-Chuan

    2014-01-01

    Three-dimensional organoids have been recently established from various tissue-specific progenitors (such as intestinal stem cells), induced pluripotent stem cells, or embryonic stem cells. These cultured self-sustaining stem cell-based organoids may become valuable systems to study the roles of tissue-specific stem cells in tissue genesis and disease development. It is thus conceivable that effective genetic manipulations in such organoids may allow us to reconstruct disease processes and/or develop novel therapeutics. Recombinant adenoviruses are one of the most commonly used viral vectors for in vitro and in vivo gene deliveries. In this study, we investigate if adenoviruses can be used to effectively deliver transgenes into the cultured "mini-gut" organoids derived from intestinal stem cells. Using adenoviral vectors that express fluorescent proteins, we demonstrate that adenoviruses can effectively deliver transgenes into the cultured 3-D "mini-gut" organoids. The transgene expression can last at least 10 days in the cultured organoids. As a proof-of-principle experiment, we demonstrate that adenovirus-mediated noggin expression effectively support the survival and self-renewal of mini-gut organoids, while adenovirus-mediated expression of BMP4 inhibits the self-sustainability and proliferation of the organoids. Thus, our results strongly suggest that adenovirus vectors can be explored as effective gene delivery vehicles to introduce genetic manipulations in 3-D organoids. PMID:24695466

  14. Identification of novel rabbit hemorrhagic disease virus B-cell epitopes and their interaction with host histo-blood group antigens.

    PubMed

    Song, Yanhua; Wang, Fang; Fan, Zhiyu; Hu, Bo; Liu, Xing; Wei, Houjun; Xue, Jiabin; Xu, Weizhong; Qiu, Rulong

    2016-02-01

    Rabbit haemorrhagic disease, caused by rabbit hemorrhagic disease virus (RHDV), results in the death of millions of adult rabbits worldwide, with a mortality rate that exceeds 90%. The sole capsid protein, VP60, is divided into shell (S) and protruding (P) domains, and the more exposed P domain likely contains determinants for cell attachment and antigenic diversity. Nine mAbs against VP60 were screened and identified. To map antigenic epitopes, a set of partially overlapping and consecutive truncated proteins spanning VP60 were expressed. The minimal determinants of the linear B-cell epitopes of VP60 in the P domain, N(326)PISQV(331), D(338)MSFV(342) and K(562)STLVFNL(569), were recognized by one (5H3), four (1B8, 3D11, 4C2 and 4G2) and four mAbs (1D4, 3F7, 5G2 and 6B2), respectively. Sequence alignment showed epitope D(338)MSFV(342) was conserved among all RHDV isolates. Epitopes N(326)PISQV(331) and K(562)STLVFNL(569) were highly conserved among RHDV G1-G6 and variable in RHDV2 strains. Previous studies demonstrated that native viral particles and virus-like particles (VLPs) of RHDV specifically bound to synthetic blood group H type 2 oligosaccharides. We established an oligosaccharide-based assay to analyse the binding of VP60 and epitopes to histo-blood group antigens (HBGAs). Results showed VP60 and its epitopes (aa 326-331 and 338-342) in the P2 subdomain could significantly bind to blood group H type 2. Furthermore, mAbs 1B8 and 5H3 could block RHDV VLP binding to synthetic H type 2. Collectively, these two epitopes might play a key role in the antigenic structure of VP60 and interaction of RHDV and HBGA. PMID:26612210

  15. Antigenic profile of African horse sickness virus serotype 4 VP5 and identification of a neutralizing epitope shared with bluetongue virus and epizootic hemorrhagic disease virus.

    PubMed

    Martínez-Torrecuadrada, J L; Langeveld, J P; Venteo, A; Sanz, A; Dalsgaard, K; Hamilton, W D; Meloen, R H; Casal, J I

    1999-05-10

    African horse sickness virus (AHSV) causes a fatal disease in horses. The virus capsid is composed of a double protein layer, the outermost of which is formed by two proteins: VP2 and VP5. VP2 is known to determine the serotype of the virus and to contain the neutralizing epitopes. The biological function of VP5, the other component of the capsid, is unknown. In this report, AHSV VP5, expressed in insect cells alone or together with VP2, was able to induce AHSV-specific neutralizing antibodies. Moreover, two VP5-specific monoclonal antibodies (MAbs) that were able to neutralize the virus in a plaque reduction assay were generated. To dissect the antigenic structure of AHSV VP5, the protein was cloned in Escherichia coli using the pET3 system. The immunoreactivity of both MAbs, and horse and rabbit polyclonal antisera, with 17 overlapping fragments from VP5 was analyzed. The most immunodominant region was found in the N-terminal 330 residues of VP5, defining two antigenic regions, I (residues 151-200) and II (residues 83-120). The epitopes were further defined by PEPSCAN analysis with 12mer peptides, which determined eight antigenic sites in the N-terminal half of the molecule. Neutralizing epitopes were defined at positions 85-92 (PDPLSPGE) for MAb 10AE12 and at 179-185 (EEDLRTR) for MAb 10AC6. Epitope 10AE12 is highly conserved between the different orbiviruses. MAb 10AE12 was able to recognize bluetongue virus VP5 and epizootic hemorrhagic disease virus VP5 by several techniques. These data will be especially useful for vaccine development and diagnostic purposes. PMID:10329555

  16. Intraventricular hemorrhage of the newborn

    MedlinePlus

    ... Grade 1 is also referred to as germinal matrix hemorrhage (GMH). Grades 3 and 4 involve more ... 2015:chap 60. Volpe JJ. Intracranial hemorrhage: germinal matrix-intraventricular hemorrhage. In Volpe JJ, ed. Neurology of ...

  17. Vaccine Design: Replication-Defective Adenovirus Vectors.

    PubMed

    Zhou, Xiangyang; Xiang, Zhiquan; Ertl, Hildegund C J

    2016-01-01

    Replication-defective adenovirus (Ad) vectors were initially developed for gene transfer for correction of genetic diseases. Although Ad vectors achieved high levels of transgene product expression in a variety of target cells, expression of therapeutic proteins was found to be transient as vigorous T cell responses directed to components of the vector as well as the transgene product rapidly eliminate Ad vector-transduced cells. This opened the use of Ad vectors as vaccine carriers and by now a multitude of preclinical as well as clinical studies has shown that Ad vectors induce very potent and sustained transgene product-specific T and B cell responses. This chapter provides guidance on developing E1-deleted Ad vectors based on available viral molecular clones. Specifically, it describes methods for cloning, viral rescue and purification as well as quality control studies. PMID:27076309

  18. Comparative analysis of rabbit hemorrhagic disease virus (RHDV) and new RHDV2 virus antigenicity, using specific virus-like particles.

    PubMed

    Bárcena, Juan; Guerra, Beatriz; Angulo, Iván; González, Julia; Valcárcel, Félix; Mata, Carlos P; Castón, José R; Blanco, Esther; Alejo, Alí

    2015-01-01

    In 2010 a new Lagovirus related to rabbit haemorrhagic disease virus (RHDV) emerged in France and has since rapidly spread throughout domestic and wild rabbit populations of several European countries. The new virus, termed RHDV2, exhibits distinctive genetic, antigenic and pathogenic features. Notably, RHDV2 kills rabbits previously vaccinated with RHDV vaccines. Here we report for the first time the generation and characterization of RHDV2-specific virus-like particles (VLPs). Our results further confirmed the differential antigenic properties exhibited by RHDV and RHDV2, highlighting the need of using RHDV2-specific diagnostic assays to monitor the spread of this new virus. PMID:26403184

  19. Acute Arthritis in Crimean-Congo Hemorrhagic Fever

    PubMed Central

    Ahmeti, Salih; Ajazaj-Berisha, Lindita; Halili, Bahrije; Shala, Anita

    2014-01-01

    Crimean-Congo hemorrhagic fever is a severe viral disease caused by a Nairovirus. An atypical manifestation in the form of acute arthritis was found in a confirmed Crimean-Congo hemorrhagic fever virus Kosova-Hoti strain positive patient. Acute arthritis in Crimean-Congo hemorrhagic fever (CCHF) may be as a result of immune mechanisms or the bleeding disorder underlying CCHF. PMID:24926169

  20. Canine adenovirus downstream processing protocol.

    PubMed

    Puig, Meritxell; Piedra, Jose; Miravet, Susana; Segura, María Mercedes

    2014-01-01

    Adenovirus vectors are efficient gene delivery tools. A major caveat with vectors derived from common human adenovirus serotypes is that most adults are likely to have been exposed to the wild-type virus and exhibit active immunity against the vectors. This preexisting immunity limits their clinical success. Strategies to circumvent this problem include the use of nonhuman adenovirus vectors. Vectors derived from canine adenovirus type 2 (CAV-2) are among the best-studied representatives. CAV-2 vectors are particularly attractive for the treatment of neurodegenerative disorders. In addition, CAV-2 vectors have shown great promise as oncolytic agents in virotherapy approaches and as vectors for recombinant vaccines. The rising interest in CAV-2 vectors calls for the development of scalable GMP compliant production and purification strategies. A detailed protocol describing a complete scalable downstream processing strategy for CAV-2 vectors is reported here. Clarification of CAV-2 particles is achieved by microfiltration. CAV-2 particles are subsequently concentrated and partially purified by ultrafiltration-diafiltration. A Benzonase(®) digestion step is carried out between ultrafiltration and diafiltration operations to eliminate contaminating nucleic acids. Chromatography purification is accomplished in two consecutive steps. CAV-2 particles are first captured and concentrated on a propyl hydrophobic interaction chromatography column followed by a polishing step using DEAE anion exchange monoliths. Using this protocol, high-quality CAV-2 vector preparations containing low levels of contamination with empty viral capsids and other inactive vector forms are typically obtained. The complete process yield was estimated to be 38-45 %. PMID:24132487

  1. [Factor VII deficiency revealed by intracranial hemorrhage].

    PubMed

    Sfaihi Ben Mansour, L; Thabet, A; Aloulou, H; Turki, H; Chabchoub, I; Mhiri, F; Mnif, Z; Ben Ali, H; Kammoun, T; Hachicha, M

    2009-07-01

    Constitutional factor VII deficiency is a hereditary disease with recessive autosomic transmission. Its incidence is estimated to be 1/1,000,000 in the general population. We report a case of severe factor VII deficiency in infancy revealed by an intracranial hemorrhage in a 2-month-old infant. We describe the clinical, biological and therapeutic characteristics of this disease. PMID:19409767

  2. Thalamic infarcts and hemorrhages.

    PubMed

    Amici, Serena

    2012-01-01

    The anatomy and supply of thalamic arteries are briefly described here. Thalamic infarcts and small-size hemorrhages are classified according to their sites: (1) posterolateral, (2) anterolateral, (3) medial, and (4) dorsal. (1) Posterolateral hemorrhages or lateral thalamic infarcts are usually characterized by severe motor impairment and sensory loss. Transient reduced consciousness, vertical-gaze abnormalities, and small fixed pupils may be evidenced. (2) Patients with anterolateral hemorrhages or tuberothalamic artery infarcts present frontal-type neuropsychological symptoms associated with mild hemiparesis and hemihypesthesia. (3) Medially located hemorrhages or paramedian artery infarcts have decreased levels of consciousness, vertical- and horizontal-gaze abnormalities, amnesia, and abulia. (4) Dorsal hemorrhages or posterior choroidal artery infarcts present with minimal transient hemiparesis and hemihypesthesia; apraxia, aphasia, and amnesia have also been described. PMID:22377880

  3. Conformational and Thermal Stability Improvements for the Large-Scale Production of Yeast-Derived Rabbit Hemorrhagic Disease Virus-Like Particles as Multipurpose Vaccine

    PubMed Central

    Méndez, Lídice; González, Nemecio; Parra, Francisco; Martín-Alonso, José M.; Limonta, Miladys; Sánchez, Kosara; Cabrales, Ania; Estrada, Mario P.; Rodríguez-Mallón, Alina; Farnós, Omar

    2013-01-01

    Recombinant virus-like particles (VLP) antigenically similar to rabbit hemorrhagic disease virus (RHDV) were recently expressed at high levels inside Pichia pastoris cells. Based on the potential of RHDV VLP as platform for diverse vaccination purposes we undertook the design, development and scale-up of a production process. Conformational and stability issues were addressed to improve process control and optimization. Analyses on the structure, morphology and antigenicity of these multimers were carried out at different pH values during cell disruption and purification by size-exclusion chromatography. Process steps and environmental stresses in which aggregation or conformational instability can be detected were included. These analyses revealed higher stability and recoveries of properly assembled high-purity capsids at acidic and neutral pH in phosphate buffer. The use of stabilizers during long-term storage in solution showed that sucrose, sorbitol, trehalose and glycerol acted as useful aggregation-reducing agents. The VLP emulsified in an oil-based adjuvant were subjected to accelerated thermal stress treatments. None to slight variations were detected in the stability of formulations and in the structure of recovered capsids. A comprehensive analysis on scale-up strategies was accomplished and a nine steps large-scale production process was established. VLP produced after chromatographic separation protected rabbits against a lethal challenge. The minimum protective dose was identified. Stabilized particles were ultimately assayed as carriers of a foreign viral epitope from another pathogen affecting a larger animal species. For that purpose, a linear protective B-cell epitope from Classical Swine Fever Virus (CSFV) E2 envelope protein was chemically coupled to RHDV VLP. Conjugates were able to present the E2 peptide fragment for immune recognition and significantly enhanced the peptide-specific antibody response in vaccinated pigs. Overall these results

  4. [Disparity of apoptotic response in human breast cancer cell lines MCF-7 and MDA-MB-231 after infection with recombinant adenovirus encoding the VP2 gene of infectious bursail disease virus].

    PubMed

    Shin, Tan Seok; Allaudin, Zeenathul Nazariah; Lila, Mohd-Azmi Mohd; Rahman, Sheikh-Omar Abdul

    2014-01-01

    Recombinant adenovirus encoding the VP2 gene of infectious bursal disease virus (ADV-VP2) has shown potent anti-tumour effects due to its capability of apoptotic induction in cancer cells. In the present study, human breast cancer cells MCF-7 and MDA-MB-231 were infected with ADV-VP2. The expression of VP2 protein was registered 4 h post-infection, particularly in MCF-7 cells. Multiple time-point DNA ladder assay demonstrated that ADV-VP2 infected MDA-MB-231 and MCF-7 cells endured apoptosis as early as 8 and 12 h post-infection, respectively. Apoptosis induction in both MDA-MB-231 and MCF-7 cells, albeit different start points, lasted til 36 h post-infection. The induction of apoptosis by ADV-VP2 was further shown by the TUNEL assay, with dark brown discoloration of apoptotic cells. The present study also explored the different stages of apoptosis by Annexin V/PI double staining flow cytometry quantification. Treated MCF-7 and MDA-MB-231 cells, respectively detected 25.58 +/- 9.02 and 14.51 +/- 3.12% of early apoptotic cells, 6.09 +/- 4.06 and 77.12 +/- 5.09% of late apoptotic cells. Results revealed that there were significant differences in the number of cells of both types which underwent early and late apoptosis. Significant differences were also observed among viable and apoptotic cells which have been post treated with ADV-VP2. The apoptotic effects of ADV-VP2 on human breast cancer cell lines were consistently demonstrated by three apoptosis detection methods. Therefore, a cancer vaccine basing on gene therapy could be developed in the near future using the present construct. PMID:25842834

  5. Gene Delivery by Subconjunctival Injection of Adenovirus in Rats: A Study of Local Distribution, Transgene Duration and Safety

    PubMed Central

    Lee, Jia Hui; Tsai, Pei-Jhen; Tsai, Han-En; Sheu, Shwu-Jiuan; Lin, Hsiu-Chen; Dusting, Gregory J.; Tai, Ming-Hong; Bee, Youn-Shen

    2015-01-01

    -term ocular transgene expression, without causing hepatic injury and immune activation. Therefore, subconjunctivally administered adenovirus may be a promising gene delivery approach for managing anterior and posterior segment eye diseases requiring short-term therapy. PMID:26642208

  6. Novel bat adenoviruses with an extremely large E3 gene.

    PubMed

    Tan, Bing; Yang, Xing-Lou; Ge, Xing-Yi; Peng, Cheng; Zhang, Yun-Zhi; Zhang, Li-Biao; Shi, Zheng-Li

    2016-07-01

    Bats carry diverse RNA viruses, some of which are responsible for human diseases. Compared to bat-borne RNA viruses, relatively little information is known regarding bat-borne DNA viruses. In this study, we isolated and characterized three novel bat adenoviruses (BtAdV WIV9-11) from Rhinolophus sinicus. Their genomes, which are highly similar to each other but distinct from those of previously sequenced adenoviruses (AdVs), are 37 545, 37 566 and 38 073 bp in size, respectively. An unusually large E3 gene was identified in their genomes. Phylogenetic and taxonomic analyses suggested that these isolates represent a distinct species of the genus Mastadenovirus. Cell susceptibility assays revealed a broad cell tropism for these isolates, indicating that they have a potentially wide host range. Our results expand the understanding of genetic diversity of bat AdVs. PMID:27032099

  7. Intratumoral Hemorrhage in a Patient With Cerebellar Hemangioblastoma

    PubMed Central

    Wang, Zhen; Hu, Jun; Xu, Liang; Malaguit, Jay; Chen, Sheng

    2015-01-01

    Abstract Spontaneous hemorrhage is rarely associated with hemangioblastomas. Intratumoral hemorrhage occurring in cerebellar hemangioblastomas is more rare. A 25-year-old man was admitted to our hospital with headache. We found a round cystic lesion with solid part in the right cerebellum. The lesion was resected. The final pathological diagnosis was hemangioblastomas. The radiological features of this case were similar to normal hemangioblastomas, whereas our histological examination showed the occurrence of the intratumoral hemorrhage. If the hemangioblastoma ruptures in our case, the outcome of the patient will be worse. It is difficult to identify the intratumoral hemorrhage of hemangioblastomas and quite dangerous if it is diagnosed late. Diagnosing an intratumoral hemorrhage of hemangioblastomas still needs a further discussion. Genetic screening may help us make an early diagnosis. Furthermore, the mechanism about intratumoral hemorrhage of hemangioblastomas remains unknown. The mutation of D6Mit135 gene on chromosome 6 may be responsible for the vascular dilation and hemorrhage induction in the hemangioblastomas. Tumor size, upregulation of vascular endothelial growth factor, spinalradicular location, and solid type are also factors relating to the hemorrhage of hemangioblastomas. The purpose of reporting our case is 2-fold: to remind clinicians to consider the possibility of internal hemorrhaging while diagnosing this disease, and provide a starting point to discuss mechanisms regarding the intratumoral hemorrhage of hemangioblastomas. PMID:25634201

  8. Falcon adenovirus infection in breeding Taita falcons (Falco fasciinucha).

    PubMed

    Dean, Jason; Latimer, Kenneth S; Oaks, J Lindsay; Schrenzel, Mark; Redig, Patrick T; Wünschmann, Arno

    2006-05-01

    Four female and 3 male Taita falcons (Falco fasciinucha) out of a breeding colony of 14 Taita falcons (7 pairs) died during the breeding season after showing lethargy and anorexia for 1 to 2 days. All animals were submitted for necropsy. Gross lesions in the female falcons were characterized by anemia secondary to marked hemorrhage into the ovary and oviduct, serofibrinous effusion into the cardioabdominal cavity and serosal petechiae. In addition, marked necrotizing splenitis and pulmonary hemorrhage were present. Histologically, the female falcons had mild necrotizing hepatitis with numerous intranuclear inclusion bodies and necrotizing splenitis with rare inclusion bodies. There were no gross lesions in the male falcons, and the histological lesions were characterized by urate deposition and rare intranuclear inclusion bodies in the renal tubular epithelial cells. Adenoviral particles were found by electron microscopy in the cloacal contents of the female Taita falcons but not in the male falcons. DNA in situ hybridization revealed widespread aviadenoviral nucleic acid within the nuclei of hepatocytes, renal tubular epithelial cells, and adrenal cells in the female falcons but no aviadenoviral nucleic acid in 1 male falcon and only a low quantity of adenoviral nucleic acid in the liver and kidney of another male Taita falcon. PCR amplified aviadenoviral DNA in the liver and intestine of all Taita falcons. The amplicons were sequenced, and the virus was identified as falcon adenovirus. The deaths of the female and male birds were attributed to the aviadenovirus infection. PMID:16789719

  9. Dabigatran-Associated Intracranial Hemorrhage

    PubMed Central

    Szarlej, Dorota K.; Rincon, Fred

    2015-01-01

    Dabigatran etexilate is an oral direct thrombin inhibitor approved for prevention of stroke and systemic embolization in patients with nonvalvular atrial fibrillation and for the treatment of venous thromboembolism. Although dabigatran has a favorable safety profile, predictable pharmacokinetics, fewer drug interactions than warfarin, and does not require monitoring, clinical data regarding dabigatran reversal are limited. In addition, currently available laboratory assays allow measurement of the presence, but not extent, of dabigatran-associated anticoagulation. Patient age, renal function, weight, concurrent drug therapy, adherence, and concomitant disease states can affect dabigatran’s efficacy and safety. Management of dabigatran-related intracranial hemorrhage must be approached on a case-by-case basis and include assessment of degree of anticoagulation, severity of hemorrhage, renal function, timing of last dabigatran dose, and risk of thromboembolic events. Initial management includes dabigatran discontinuation and general supportive measures. Oral activated charcoal should be administered in those who ingested dabigatran within 2 hours. Four-factor prothrombin complex concentrates (4PCCs), activated PCC, or recombinant activated factor VII use may be reasonable but is not evidence based. Reserve fresh frozen plasma for patients with dilutional coagulopathy. If readily available, hemodialysis should be considered, particularly in patients with advanced kidney injury or excessive risk of thromboembolic events. More clinical studies are needed to determine a standardized approach to treating dabigatran-associated intracranial hemorrhage. Institutional protocol development will facilitate safe, efficacious, and timely use of the limited management options. PMID:26425251

  10. Neofunctionalization of the Sec1 α1,2fucosyltransferase paralogue in leporids contributes to glycan polymorphism and resistance to rabbit hemorrhagic disease virus.

    PubMed

    Nyström, Kristina; Abrantes, Joana; Lopes, Ana Margarida; Le Moullac-Vaidye, Béatrice; Marchandeau, Stéphane; Rocher, Jézabel; Ruvoën-Clouet, Nathalie; Esteves, Pedro J; Le Pendu, Jacques

    2015-04-01

    RHDV (rabbit hemorrhagic disease virus), a virulent calicivirus, causes high mortalities in European rabbit populations (Oryctolagus cuniculus). It uses α1,2fucosylated glycans, histo-blood group antigens (HBGAs), as attachment factors, with their absence or low expression generating resistance to the disease. Synthesis of these glycans requires an α1,2fucosyltransferase. In mammals, there are three closely located α1,2fucosyltransferase genes rSec1, rFut2 and rFut1 that arose through two rounds of duplications. In most mammalian species, Sec1 has clearly become a pseudogene. Yet, in leporids, it does not suffer gross alterations, although we previously observed that rabbit Sec1 variants present either low or no activity. Still, a low activity rSec1 allele correlated with survival to an RHDV outbreak. We now confirm the association between the α1,2fucosyltransferase loci and survival. In addition, we show that rabbits express homogenous rFut1 and rFut2 levels in the small intestine. Comparison of rFut1 and rFut2 activity showed that type 2 A, B and H antigens recognized by RHDV strains were mainly synthesized by rFut1, and all rFut1 variants detected in wild animals were equally active. Interestingly, rSec1 RNA levels were highly variable between individuals and high expression was associated with low binding of RHDV strains to the mucosa. Co-transfection of rFut1 and rSec1 caused a decrease in rFut1-generated RHDV binding sites, indicating that in rabbits, the catalytically inactive rSec1 protein acts as a dominant-negative of rFut1. Consistent with neofunctionalization of Sec1 in leporids, gene conversion analysis showed extensive homogenization between Sec1 and Fut2 in leporids, at variance with its limited degree in other mammals. Gene conversion additionally involving Fut1 was also observed at the C-terminus. Thus, in leporids, unlike in most other mammals where it became extinct, Sec1 evolved a new function with a dominant-negative effect on rFut1

  11. Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

    DOE PAGESBeta

    Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; Borducchi, Erica N.; Iampietro, M. Justin; Bricault, Christine A.; Teigler, Jeffrey E.; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; et al

    2014-11-19

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved tomore » have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.« less

  12. Construction and Evaluation of Novel Rhesus Monkey Adenovirus Vaccine Vectors

    SciTech Connect

    Abbink, Peter; Maxfield, Lori F.; Ng'ang'a, David; Borducchi, Erica N.; Iampietro, M. Justin; Bricault, Christine A.; Teigler, Jeffrey E.; Blackmore, Stephen; Parenteau, Lily; Wagh, Kshitij; Handley, Scott A.; Zhao, Guoyan; Virgin, Herbert W.; Korber, Bette; Barouch, Dan H.

    2014-11-19

    Adenovirus vectors are widely used as vaccine candidates for a variety of pathogens, including HIV-1. To date, human and chimpanzee adenoviruses have been explored in detail as vaccine vectors. Furthermore, the phylogeny of human and chimpanzee adenoviruses is overlapping, and preexisting humoral and cellular immunity to both are exhibited in human populations worldwide. More distantly related adenoviruses may therefore offer advantages as vaccine vectors. We describe the primary isolation and vectorization of three novel adenoviruses from rhesus monkeys. The seroprevalence of these novel rhesus monkey adenovirus vectors was extremely low in sub-Saharan Africa human populations, and these vectors proved to have immunogenicity comparable to that of human and chimpanzee adenovirus vaccine vectors in mice. These rhesus monkey adenoviruses phylogenetically clustered with the poorly described adenovirus species G and robustly stimulated innate immune responses. These novel adenoviruses represent a new class of candidate vaccine vectors.

  13. Simultaneous detection of astrovirus, rotavirus, reovirus and adenovirus type I in broiler chicken flocks.

    PubMed

    Roussan, D A; Shaheen, I A; Khawaldeh, G Y; Totanji, W S; Al-Rifai, R H

    2012-01-01

    Enteric diseases cause substantial economic losses to the poultry industry. Astroviruses, rotaviruses, reoviruses, and adenovirus type 1 have been reported as a significant cause of intestinal symptoms in poultry. In the present study, intestinal samples from 70 commercial broiler chicken flocks were examined for the presence of astroviruses, rotavirus, and reovirus by reverse transcription-polymerase chain reaction, and for the presence of group I adenovirus by polymerase chain reaction. Astroviruses were identified in 38.6% of samples tested. Both avian nephritis virus and chicken astrovirus were identified in the astrovirus positive flocks, where 74.1% of these flocks were positive for only one type of astrovirus, whereas, 25.9% of these flocks were positive for both types of astrovirus. Reoviruses, rotaviruses, and adenoviruses were identified in 21.4, 18.6, and 14.3% of these flocks, respectively. Concomitant infection with two or more viruses in the same flock were also prominent, where 5.7, 5.7, 2.9, 2.9, 1.4, and 1.4% of these flocks were positive with both astrovirus and rotavirus; astrovirus and adenovirus; astrovirus and reovirus; rotavirus and adenovirus; rotavirus and reovirus; and reovirus and adenovirus respectively. Moreover, 4.3 and 2.7% of these flocks were positive for astrovirus, reovirus, and adenovirus; and astrovirus, reovirus, and rotavirus, respectively. Further studies will focus on identifying specific viral factors or subtypes/subgroups associated with disease through pathogenesis studies, economic losses caused by infections and co-infections of these pathogens, and the costs and benefits of countermeasures. PMID:22844713

  14. Hereditary Hemorrhagic Telangiectasia - HHT

    MedlinePlus

    ... Throughout Body Hereditary Hemorrhagic Telangiectasia (HHT) is a genetic disorder that affects about one in 5,000 people and causes arterial blood to flow directly into the veins, creating weakened ballooned vessels that can rupture. Interventional radiologists ...

  15. Microwave hemorrhagic stroke detector

    DOEpatents

    Haddad, Waleed S.; Trebes, James E.

    2007-06-05

    The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stoke in human or animal patients as well as for the detection of hemorrhage within a patient's body.

  16. Simian hemorrhagic fever virus

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This book chapter describes the taxonomic classification of Simian hemorrhagic fever virus (SHFV). Included are: host, genome, classification, morphology, physicochemical and physical properties, nucleic acid, proteins, lipids, carbohydrates, geographic range, phylogenetic properties, biological pro...

  17. Microwave hemorrhagic stroke detector

    DOEpatents

    Haddad, Waleed S.; Trebes, James E.

    2002-01-01

    The microwave hemorrhagic stroke detector includes a low power pulsed microwave transmitter with a broad-band antenna for producing a directional beam of microwaves, an index of refraction matching cap placed over the patients head, and an array of broad-band microwave receivers with collection antennae. The system of microwave transmitter and receivers are scanned around, and can also be positioned up and down the axis of the patients head. The microwave hemorrhagic stroke detector is a completely non-invasive device designed to detect and localize blood pooling and clots or to measure blood flow within the head or body. The device is based on low power pulsed microwave technology combined with specialized antennas and tomographic methods. The system can be used for rapid, non-invasive detection of blood pooling such as occurs with hemorrhagic stroke in human or animal patients as well as for the detection of hemorrhage within a patient's body.

  18. Hemorrhagic disease of the newborn

    MedlinePlus

    ... newborn. Vitamin K plays an important role in blood clotting. Babies often have low levels of vitamin K ... Blood clotting tests will be done. The diagnosis is confirmed if a vitamin K shot stops the bleeding ...

  19. Infection by retroviral vectors outside of their host range in the presence of replication-defective adenovirus.

    PubMed Central

    Adams, R M; Wang, M; Steffen, D; Ledley, F D

    1995-01-01

    Retrovirus infection is normally limited to cells within a specific host range which express a cognate receptor that is recognized by the product of the env gene. We describe retrovirus infection of cells outside of their normal host range when the infection is performed in the presence of a replication-defective adenovirus (dl312). In the presence of adenovirus, several different ecotropic vectors are shown to infect human cell lines (HeLa and PLC/PRF), and a xenotropic vector is shown to infect murine cells (NIH 3T3). Infectivity is demonstrated by 5-bromo-4-chloro-3-indolyl-beta-D-galactopyranoside (X-Gal) staining, selection with G418 for neomycin resistance, and PCR identification of the provirus in infected cells. Infectivity is quantitatively dependent upon both the concentration of adenovirus (10(6) to 10(8) PFU/ml) and the concentration of retrovirus. Infection requires the simultaneous presence of adenovirus in the retrovirus infection medium and is not stimulated by preincubation and removal of adenovirus from the cells before retrovirus infection. The presence of adenovirus is shown to enhance the uptake of fluorescently labeled retrovirus particles into cells outside of their normal host range, demonstrating that the adenovirus enhances viral entry into cells in the absence of the recognized cognate receptor. This observation suggests new opportunities for developing safe retroviral vectors for gene therapy and new mechanisms for the pathogenesis of retroviral disease. PMID:7853530

  20. Oncolytic adenovirus-mediated therapy for prostate cancer.

    PubMed

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen-androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses. PMID:27579296

  1. Oncolytic adenovirus-mediated therapy for prostate cancer

    PubMed Central

    Sweeney, Katrina; Halldén, Gunnel

    2016-01-01

    Prostate cancer is a leading cause of cancer-related death and morbidity in men in the Western world. Tumor progression is dependent on functioning androgen receptor signaling, and initial administration of antiandrogens and hormone therapy (androgen-deprivation therapy) prevent growth and spread. Tumors frequently develop escape mechanisms to androgen-deprivation therapy and progress to castration-resistant late-stage metastatic disease that, in turn, inevitably leads to resistance to all current therapeutics, including chemotherapy. In spite of the recent development of more effective inhibitors of androgen–androgen receptor signaling such as enzalutamide and abiraterone, patient survival benefits are still limited. Oncolytic adenoviruses have proven efficacy in prostate cancer cells and cause regression of tumors in preclinical models of numerous drug-resistant cancers. Data from clinical trials demonstrate that adenoviral mutants have limited toxicity to normal tissues and are safe when administered to patients with various solid cancers, including prostate cancer. While efficacy in response to adenovirus administration alone is marginal, findings from early-phase trials targeting local-ized and metastatic prostate cancer suggest improved efficacy in combination with cytotoxic drugs and radiation therapy. Here, we review recent progress in the development of multimodal oncolytic adenoviruses as biological therapeutics to improve on tumor elimination in prostate cancer patients. These optimized mutants target cancer cells by several mechanisms including viral lysis and by expression of cytotoxic transgenes and immune-stimulatory factors that activate the host immune system to destroy both infected and noninfected prostate cancer cells. Additional modifications of the viral capsid proteins may support future systemic delivery of oncolytic adenoviruses. PMID:27579296

  2. Phylogenetic analysis of adenovirus sequences.

    PubMed

    Harrach, Balázs; Benko, Mária

    2007-01-01

    Members of the family Adenoviridae have been isolated from a large variety of hosts, including representatives from every major vertebrate class from fish to mammals. The high prevalence, together with the fairly conserved organization of the central part of their genomes, make the adenoviruses one of (if not the) best models for studying viral evolution on a larger time scale. Phylogenetic calculation can infer the evolutionary distance among adenovirus strains on serotype, species, and genus levels, thus helping the establishment of a correct taxonomy on the one hand, and speeding up the process of typing new isolates on the other. Initially, four major lineages corresponding to four genera were recognized. Later, the demarcation criteria of lower taxon levels, such as species or types, could also be defined with phylogenetic calculations. A limited number of possible host switches have been hypothesized and convincingly supported. Application of the web-based BLAST and MultAlin programs and the freely available PHYLIP package, along with the TreeView program, enables everyone to make correct calculations. In addition to step-by-step instruction on how to perform phylogenetic analysis, critical points where typical mistakes or misinterpretation of the results might occur will be identified and hints for their avoidance will be provided. PMID:17656792

  3. Anti-Viral Drugs for Human Adenoviruses

    PubMed Central

    Waye, Mary Miu Yee; Sing, Chor Wing

    2010-01-01

    There are many stages in the development of a new drug for viral infection and such processes are even further complicated for adenovirus by the fact that there are at least 51 serotypes, forming six distinct groups (A–F), with different degree of infectivity. This review attempts to address the importance of developing pharmaceuticals for adenovirus and also review recent development in drug discovery for adenovirus, including newer strategies such as microRNA approaches. Different drug screening strategies will also be discussed.

  4. Human adenovirus: Viral pathogen with increasing importance

    PubMed Central

    2014-01-01

    The aim of this review is to describe the biology of human adenovirus (HAdV), the clinical and epidemiological characteristics of adenoviral epidemic keratoconjunctivitis and to present a practical update on its diagnosis, treatment, and prophylaxis. There are two well-defined adenoviral keratoconjunctivitis clinical syndromes: epidemic keratoconjunctivitis (EKC) and pharyngoconjunctival fever (PCF), which are caused by different HAdV serotypes. The exact incidence of adenoviral conjunctivitis is still poorly known. However, cases are more frequent during warmer months. The virus is endemic in the general population, and frequently causes severe disease in immunocompromised patients, especially the pediatric patients. Contagion is possible through direct contact or fomites, and the virus is extremely resistant to different physical and chemical agents. The clinical signs or symptoms of conjunctival infection are similar to any other conjunctivitis, with a higher incidence of pseudomembranes. In the cornea, adenoviral infection may lead to keratitis nummularis. Diagnosis is mainly clinical, but its etiology can be confirmed using cell cultures, antigen detection, polymerase chain reaction or immunochromatography. Multiple treatments have been tried for this disease, but none of them seem to be completely effective. Prevention is the most reliable and recommended strategy to control this contagious infection. PMID:24678403

  5. An outbreak of adenovirus keratoconjunctivitis in bristol.

    PubMed Central

    Tullo, A B; Higgins, P G

    1979-01-01

    Nineteen cases of keratoconjunctivitis caused by an adenovirus serologically related to types 10 and 19 are described. Seventeen of the patients presented over a period of 7 weeks and included 4 who were involved in a minor outbreak at a factory. The presentation and clinical features closely resembled those caused by adenoviruses types 8 and 19. Mild to severe follicular conjunctivitis, superficial punctate keratitis, discrete subepithelial opacities, membrane formation, and conjunctival scarring were all observed. Images PMID:226115

  6. Technical aspects of using human adenovirus as a viral water quality indicator.

    PubMed

    Rames, Emily; Roiko, Anne; Stratton, Helen; Macdonald, Joanne

    2016-06-01

    Despite dramatic improvements in water treatment technologies in developed countries, waterborne viruses are still associated with many of cases of illness each year. These illnesses include gastroenteritis, meningitis, encephalitis, and respiratory infections. Importantly, outbreaks of viral disease from waters deemed compliant from bacterial indicator testing still occur, which highlights the need to monitor the virological quality of water. Human adenoviruses are often used as a viral indicator of water quality (faecal contamination), as this pathogen has high UV-resistance and is prevalent in untreated domestic wastewater all year round, unlike enteroviruses and noroviruses that are often only detected in certain seasons. Standard methods for recovering and measuring adenovirus numbers in water are lacking, and there are many variations in published methods. Since viral numbers are likely under-estimated when optimal methods are not used, a comprehensive review of these methods is both timely and important. This review critically evaluates how estimates of adenovirus numbers in water are impacted by technical manipulations, such as during adenovirus concentration and detection (including culturing and polymerase-chain reaction). An understanding of the implications of these issues is fundamental to obtaining reliable estimation of adenovirus numbers in water. Reliable estimation of HAdV numbers is critical to enable improved monitoring of the efficacy of water treatment processes, accurate quantitative microbial risk assessment, and to ensure microbiological safety of water. PMID:27065054

  7. Identification and Application of Neutralizing Epitopes of Human Adenovirus Type 55 Hexon Protein

    PubMed Central

    Tian, Xingui; Ma, Qiang; Jiang, Zaixue; Huang, Junfeng; Liu, Qian; Lu, Xiaomei; Luo, Qingming; Zhou, Rong

    2015-01-01

    Human adenovirus type 55 (HAdV55) is a newly identified re-emergent acute respiratory disease (ARD) pathogen with a proposed recombination of hexon gene between HAdV11 and HAdV14 strains. The identification of the neutralizing epitopes is important for the surveillance and vaccine development against HAdV55 infection. In this study, four type-specific epitope peptides of HAdV55 hexon protein, A55R1 (residues 138 to 152), A55R2 (residues 179 to 187), A55R4 (residues 247 to 259) and A55R7 (residues 429 to 443), were predicted by multiple sequence alignment and homology modeling methods, and then confirmed with synthetic peptides by enzyme-linked immunosorbent assay (ELISA) and neutralization tests (NT). Finally, the A55R2 was incorporated into human adenoviruses 3 (HAdV3) and a chimeric adenovirus rAd3A55R2 was successfully obtained. The chimeric rAd3A55R2 could induce neutralizing antibodies against both HAdV3 and HAdV55. This current study will contribute to the development of novel adenovirus vaccine candidate and adenovirus structural analysis. PMID:26516903

  8. Optimization and evaluation of a method to detect adenoviruses in river water.

    PubMed

    McMinn, Brian R; Korajkic, Asja; Grimm, Ann C

    2016-05-01

    Adenoviruses are often implicated in recreational water disease outbreaks but existing methods for their detection perform poorly within these matrices. In this study, small volume (100mL) concentration was used to identify processes that promoted recovery of adenovirus from river water. Several alternative secondary concentration techniques were investigated and compared to the baseline method consisting of primary concentration via filtration, followed by celite mediated secondary concentration. The alternative secondary concentrations included multiple filter elutions, soaking the filter for 15min prior to elution and concentration using pre-treated celite (river water, 1.5% and 3% milk) instead of a filter. Modifications of the viral nucleic acid extraction technique were also evaluated. Concentration using pre-treated celite and a modified extraction technique (10min boil and a 1h ProK incubation at 37°C) recovered significantly higher levels of adenovirus (P=0.001) than other methods tested. This optimized method increased recovery of spiked adenovirus (57±27%) compared to baseline method performance (4±3%) indicating that use of pre-treated celite as opposed to filtration significantly improves recovery. Application of the optimized concentration method to larger volume (1L) of river water resulted in similar recoveries (42±19%) underlying the utility of this method to detect adenovirus from environmental samples. PMID:26874286

  9. Marburg Hemorrhagic Fever (Marburg HF)

    MedlinePlus

    ... The CDC Cancel Submit Search The CDC Marburg hemorrhagic fever (Marburg HF) Note: Javascript is disabled or is ... was first recognized in 1967, when outbreaks of hemorrhagic fever occurred simultaneously in laboratories in Marburg and Frankfurt, ...

  10. PRIMARY POSTPARTUM HEMORRHAGE

    PubMed Central

    Melody, George F.

    1951-01-01

    Postpartum hemorrhage is the outstanding cause of maternal mortality, and a redoubtable contributor to puerperal death from other causes, notably infection and renal failure. The clinical situations in which hemorrhage is liable to occur must be better known, so that anticipatory and preventive measures can be taken. Recent knowledge about defibrinated blood in women with degenerative changes at the placental site must be incorporated in the thinking and practice of physicians dealing with obstetrical cases. The indications, limitations, and hazards of the various anesthetic methods available for parturient women should be carefully considered in the circumstances of each case. ImagesFigure 1.Figure 2.Figure 3. PMID:14886749

  11. Hereditary Hemorrhagic Telangiectasia.

    PubMed

    Parambil, Joseph G

    2016-09-01

    Hereditary hemorrhagic telangiectasia (HHT) is an underrecognized and underdiagnosed autosomal-dominant angiodysplasia that has an estimated prevalence of 1 in 5000 individuals, with variable clinical presentations even within family members with identical mutations. The most common manifestations are telangiectasias of the skin and nasal mucosa. However, HHT can often be complicated by the presence of arteriovenous malformations and telangiectasias in the lungs, brain, gastrointestinal tract, and liver that are often silent and can lead to life-threatening complications of stroke and hemorrhage. This article reviews HHT for the pulmonologist, who is not uncommonly the first practitioner to encounter these patients. PMID:27514597

  12. Subarachnoid Hemorrhage: An Update.

    PubMed

    Dority, Jeremy S; Oldham, Jeffrey S

    2016-09-01

    Subarachnoid hemorrhage (SAH) is a debilitating, although uncommon, type of stroke with high morbidity, mortality, and economic impact. Modern 30-day mortality is as high as 40%, and about 50% of survivors have permanent disability. Care at high-volume centers with dedicated neurointensive care units is recommended. Euvolemia, not hypervolemia, should be targeted, and the aneurysm should be secured early. Neither statin therapy nor magnesium infusions should be initiated for delayed cerebral ischemia. Cerebral vasospasm is just one component of delayed cerebral edema. Hyponatremia is common in subarachnoid hemorrhage and is associated with longer length of stay, but not increased mortality. PMID:27521199

  13. Nuclear actin and myosins in adenovirus infection.

    PubMed

    Fuchsova, Beata; Serebryannyy, Leonid A; de Lanerolle, Primal

    2015-11-01

    Adenovirus serotypes have been shown to cause drastic changes in nuclear organization, including the transcription machinery, during infection. This ability of adenovirus to subvert transcription in the host cell facilitates viral replication. Because nuclear actin and nuclear myosin I, myosin V and myosin VI have been implicated as direct regulators of transcription and important factors in the replication of other viruses, we sought to determine how nuclear actin and myosins are involved in adenovirus infection. We first confirmed reorganization of the host's transcription machinery to viral replication centers. We found that nuclear actin also reorganizes to sites of transcription through the intermediate but not the advanced late phase of viral infection. Furthermore, nuclear myosin I localized with nuclear actin and sites of transcription in viral replication centers. Intriguingly, nuclear myosins V and VI, which also reorganized to viral replication centers, exhibited different localization patterns, suggesting specialized roles for these nuclear myosins. Finally, we assessed the role of actin in adenovirus infection and found both cytoplasmic and nuclear actin likely play roles in adenovirus infection and replication. Together our data suggest the involvement of actin and multiple myosins in the nuclear replication and late viral gene expression of adenovirus. PMID:26226218

  14. Core labeling of adenovirus with EGFP

    SciTech Connect

    Le, Long P.; Le, Helen N.; Nelson, Amy R.; Matthews, David A.; Yamamoto, Masato; Curiel, David T. . E-mail: curiel@uab.edu

    2006-08-01

    The study of adenovirus could greatly benefit from diverse methods of virus detection. Recently, it has been demonstrated that carboxy-terminal EGFP fusions of adenovirus core proteins Mu, V, and VII properly localize to the nucleus and display novel function in the cell. Based on these observations, we hypothesized that the core proteins may serve as targets for labeling the adenovirus core with fluorescent proteins. To this end, we constructed various chimeric expression vectors with fusion core genes (Mu-EGFP, V-EGFP, preVII-EGFP, and matVII-EGFP) while maintaining expression of the native proteins. Expression of the fusion core proteins was suboptimal using E1 expression vectors with both conventional CMV and modified (with adenovirus tripartite leader sequence) CMV5 promoters, resulting in non-labeled viral particles. However, robust expression equivalent to the native protein was observed when the fusion genes were placed in the deleted E3 region. The efficient Ad-wt-E3-V-EGFP and Ad-wt-E3-preVII-EGFP expression vectors were labeled allowing visualization of purified virus and tracking of the viral core during early infection. The vectors maintained their viral function, including viral DNA replication, viral DNA encapsidation, cytopathic effect, and thermostability. Core labeling offers a means to track the adenovirus core in vector targeting studies as well as basic adenovirus virology.

  15. Severe Infections with Human Adenovirus 7d in 2 Adults in Family, Illinois, USA, 2014

    PubMed Central

    Ison, Michael G.

    2016-01-01

    Human adenovirus 7d, a genomic variant with no reported circulation in the United States, was isolated from 2 adults with severe respiratory infections in Illinois. Molecular typing identified a close relationship with strains of the same genome type isolated from cases of respiratory disease in several provinces of China since 2009. PMID:26982199

  16. Human adenovirus type 7 outbreak in Police Training Center, Malaysia, 2011.

    PubMed

    Yusof, Mohd Apandi; Rashid, Tengku Rogayah Tengku Abdul; Thayan, Ravindran; Othman, Khairul Azuan; Hasan, Norhasnida Abu; Adnan, Norfaezah; Saat, Zainah

    2012-05-01

    In March 2011, an outbreak of acute respiratory disease was reported at the Kuala Lumpur (Malaysia) Police Training Centre. Approximately 100 trainees were hospitalized and 5 were admitted to the intensive care unit. Three of these 5 trainees died. Human adenovirus type 7 was identified as the etiologic agent. PMID:22515984

  17. Adenovirus 36 and Obesity: An Overview

    PubMed Central

    Ponterio, Eleonora; Gnessi, Lucio

    2015-01-01

    There is an epidemic of obesity starting about 1980 in both developed and undeveloped countries definitely associated with multiple etiologies. About 670 million people worldwide are obese. The incidence of obesity has increased in all age groups, including children. Obesity causes numerous diseases and the interaction between genetic, metabolic, social, cultural and environmental factors are possible cofactors for the development of obesity. Evidence emerging over the last 20 years supports the hypothesis that viral infections may be associated with obesity in animals and humans. The most widely studied infectious agent possibly linked to obesity is adenovirus 36 (Adv36). Adv36 causes obesity in animals. In humans, Adv36 associates with obesity both in adults and children and the prevalence of Adv36 increases in relation to the body mass index. In vivo and in vitro studies have shown that the viral E4orf1 protein (early region 4 open reading frame 1, Adv) mediates the Adv36 effect including its adipogenic potential. The Adv36 infection should therefore be considered as a possible risk factor for obesity and could be a potential new therapeutic target in addition to an original way to understand the worldwide rise of the epidemic of obesity. Here, the data indicating a possible link between viral infection and obesity with a particular emphasis to the Adv36 will be reviewed. PMID:26184280

  18. Safety evaluation of adenovirus type 4 and type 7 vaccine live, oral in military recruits.

    PubMed

    Choudhry, Azhar; Mathena, Julie; Albano, Jessica D; Yacovone, Margaret; Collins, Limone

    2016-08-31

    Before the widespread adoption of vaccination, adenovirus type 4 and type 7 were long associated with respiratory illnesses among military recruits. When supplies were depleted and vaccination was suspended in 1999 for approximately a decade, respiratory illnesses due to adenovirus infections resurged. In March 2011, a new live, oral adenovirus vaccine was licensed by the US Food and Drug Administration and was first universally administered to military recruits in October 2011, leading to rapid, dramatic elimination of the disease within a few months. As part of licensure, a postmarketing study (Sentinel Surveillance Plan) was performed to detect potential safety signals within 42days after immunization of military recruits. This study retrospectively evaluated possible adverse events related to vaccination using data from the Armed Forces Health Surveillance Branch Defense Medical Surveillance System (DMSS) database. Among 100,000 recruits who received the adenovirus vaccine, no statistically significant greater risk of prespecified medical events was observed within 42days after vaccination when compared with a historical cohort of 100,000 unvaccinated recruits. In an initial statistical analysis of International Classification of Disease, 9th Revision, Clinical Modification codes, a statistically significant higher risk for 19 other (not prespecified) medical events occurring in 5 or more recruits was observed among vaccinated compared with unvaccinated groups. After case record data abstraction for attribution and validation, two events (psoriasis [21 vs 7 cases] and serum reactions [12 vs 4 cases]) occurred more frequently in the vaccinated cohort. A causal relation of these rare events with adenovirus vaccination could not be established given confounding factors in the DMSS, such as coadministration of other vaccines and incomplete or inaccurate medical information, for some recruits. Prospective surveillance assessing these uncommon, but potentially

  19. Atraumatic multifocal intracerebral hemorrhage.

    PubMed

    Fetcko, Kaleigh M; Hendricks, Benjamin K; Scott, John; Cohen-Gadol, Aaron A

    2016-09-01

    This article describes a patient with atraumatic multifocal intracerebral, subarachnoid, and bilateral frontal convexity acute subdural hematomas. The patient is a 46-year-old Caucasian man who presented with a spontaneous severe progressive headache. Following a description of the case, this article reviews the reported incidence, proposed etiology, and current management strategies for multifocal spontaneous intracerebral hemorrhage. PMID:27234608

  20. human adenoviruses role in ophthalmic pterygium formation

    PubMed Central

    Kelishadi, Mishar; Kelishadi, Mandana; Moradi, Abdolvahab; Javid, Naeme; Bazouri, Masoud; Tabarraei, Alijan

    2015-01-01

    Background: Ophthalmic pterygium is a common benign lesion of unknown origin and the pathogenesis might be vision-threatening. This problem is often associated with exposure to solar light. Recent evidence suggests that potentially oncogenic viruses such as human papillomavirus and Epstein-Barr virus may be involved in the pathogenesis of pterygia. Expression of specific adenovirus genes such as E1A and E1B, which potentially have many functions, may contribute to their oncogenic activity as well as relevance to cellular immortalization. Objectives: For the first time, we aimed to investigate involvement of adenoviruses in pterygium formation. Patients and Methods: Fifty tissue specimens of pterygium from patients undergoing pterygium surgery (as cases), 50 conjunctival swab samples from the same patients and 10 conjunctival biopsy specimens from individuals without pterygium such as patients undergoing cataract surgery (as controls) were analyzed for evidence of adenovirus infection with polymerase chain reaction using specific primers chosen from the moderately conserved region of the hexon gene. Furthermore, β-globin primers were used to access the quality of extracted DNA. Data was analyzed using SPSS (version 16) software. Results: Of 50 patients, 20 were men and 30 women with mean age of 61.1 ± 16.9 years ranged between 22 and 85 years. All samples of pterygia had positive results for adenoviruses DNA with polymerase chain reaction, but none of the negative control groups displayed adenoviruses. The pterygium group and the control groups were β-globin positive. Direct sequencing of PCR products confirmed Adenovirus infection. Conclusions: Adenoviruses might act as a possible cause of pterygium formation and other factors could play a synergistic role in the development. However, further larger studies are required to confirm this hypothesis. PMID:26034543

  1. Prohemostatic interventions in obstetric hemorrhage.

    PubMed

    Bonnet, Marie-Pierre; Basso, Olga

    2012-04-01

    Obstetric hemorrhage is a major cause of maternal morbidity and mortality. Pregnancy is associated with substantial hemostatic changes, resulting in a relatively hypercoagulable state. Acquired coagulopathy can, however, develop rapidly in severe obstetric hemorrhage. Therefore, prohemostatic treatments based on high fresh frozen plasma and red blood cell (FFP:RBC) ratio transfusion and procoagulant agents (fibrinogen concentrates, recombinant activated factor VII, and tranexamic acid) are crucial aspects of management. Often, evidence from trauma patients is applied to obstetric hemorrhage management, although distinct differences exist between the two situations. Therefore, until efficacy and safety are demonstrated in obstetric hemorrhage, clinicians should be cautious about wholesale adoption of high FFP:RBC ratio products. Applications of transfusion protocols, dedicated to massive obstetric hemorrhage and multidisciplinarily developed, currently remain the best available option. Similarly, while procoagulant agents appear promising in treatment of obstetric hemorrhage, caution is nonetheless warranted as long as clear evidence in the context of obstetric hemorrhage is lacking. PMID:22510859

  2. Pulmonary hemorrhage syndrome associated with dengue fever, High-resolution computed tomography findings: a case report

    PubMed Central

    Marchiori, Edson; Ferreira, José Luiz N; Bittencourt, Carolina N; Neto, César A de Araújo; Zanetti, Gláucia; Mano, Cláudia M; Santos, Alair ASD; Vianna, Alberto D

    2009-01-01

    Dengue hemorrhagic fever is an acute infectious disease caused by dengue virus. We described the high-resolution CT findings in a 70-year-old male with the disease, which was diagnosed by clinical examination and confirmed by serological methods. High-resolution CT demonstrated bilateral areas of consolidation with air bronchogram and ground glass opacities, as well as small bilateral pleural effusions. Dengue hemorrhagic fever should be considered in the differential diagnosis of diffuse pulmonary hemorrhage. PMID:19265524

  3. [Acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection].

    PubMed

    de Suremain, A; Somrani, R; Bourdat-Michel, G; Pinel, N; Morel-Baccard, C; Payen, V

    2015-05-01

    Acute tubulointerstitial nephritis (TIN) is responsible for nearly 10% of acute renal failure (ARF) cases in children. It is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. An immune-competent 13-month-old boy was admitted to the intensive care unit for severe ARF with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. The kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, without any signs of necrosis. There were no virus inclusion bodies, no interstitial hemorrhage, and no glomerular or vascular damage. Other causes of TIN were excluded: there was no biological argument for an immunological, immune, or drug-induced cause. Adenovirus (ADV) and respiratory syncytial virus (RSV) were positive in respiratory multiplex polymerase chain reaction (PCR) in nasal aspirate but not in blood, urine, and renal tissue. The patient underwent dialysis for 10 days but the response to corticosteroid therapy was quickly observed within 48 h. The mechanism of TIN associated with virus infection is unknown. However, it may be immune-mediated to be able to link severe renal dysfunction and ADV and/or RSV invasion of the respiratory tract. PMID:25842199

  4. Adenovirus-mediated gene transfer to ciliated airway epithelia requires prolonged incubation time.

    PubMed Central

    Zabner, J; Zeiher, B G; Friedman, E; Welsh, M J

    1996-01-01

    The efficiency of adenovirus-mediated gene transfer to airway epithelia will be an important factor in determining whether recombinant adenoviruses can be developed as vectors for transferring cystic fibrosis transmembrane conductance regulator (CFTR) cDNA to patients with cystic fibrosis. Current understanding of the biology of CF lung disease suggests that vectors should express transgene in mature, ciliated airway epithelia. We evaluated the efficiency of adenovirus-mediated gene transfer to primary cultures of normal and CF human airway epithelia. Our studies showed that the airway cells developed from an undifferentiated epithelium with markers characteristic of basal cells and a surface covered by short microvilli 3 days after seeding to a mature epithelium whose apical surface was covered with cilia by 10 to 14 days. The ability of adenovirus vectors to express a reporter gene and to correct defective cyclic AMP-stimulated Cl- transport in CF epithelia was correlated inversely with the state of differentiation. However, the inefficiency of adenovirus-mediated gene transfer could be partially corrected when the contact time between vector and epithelium was prolonged. After prolonged contact, we observed complete correction of the CF Cl- transport defect in differentiated CF airway epithelia in culture and of the Cl- transport defect in the nasal epithelia of mice homozygous for the deltaF508 mutation. The fact that gene transfer to airway epithelia required prolonged incubation with vector contrasts with the rapid infection observed in cell models such as 293 and HeLa cells, which are commonly used to study adenovirus infection. Gene transfer observed after prolonged incubation may result from mechanisms different from those that mediate infection of 293 cells. These observations suggest that interventions that either increase the contact time or alter the epithelium or the vector may be required to facilitate gene transfer to ciliated respiratory epithelia

  5. Imaging of Hereditary Hemorrhagic Telangiectasia

    SciTech Connect

    Carette, Marie-France Nedelcu, Cosmina; Tassart, Marc; Grange, Jean-Didier; Wislez, Marie; Khalil, Antoine

    2009-07-15

    This pictorial review is based on our experience of the follow-up of 120 patients at our multidisciplinary center for hereditary hemorrhagic telangiectasia (HHT). Rendu-Osler-Weber disease or HHT is a multiorgan autosomal dominant disorder with high penetrance, characterized by epistaxis, mucocutaneous telangiectasis, and visceral arteriovenous malformations (AVMs). The research on gene mutations is fundamental and family screening by clinical examination, chest X-ray, research of pulmonary shunting, and abdominal color Doppler sonography is absolutely necessary. The angioarchitecture of pulmonary AVMs can be studied by unenhanced multidetector computed tomography; however, all other explorations of liver, digestive bowels, or brain require administration of contrast media. Magnetic resonance angiography is helpful for central nervous system screening, in particular for the spinal cord, but also for pulmonary, hepatic, and pelvic AVMs. Knowledge of the multiorgan involvement of HHT, mechanism of complications, and radiologic findings is fundamental for the correct management of these patients.

  6. [Non-traumatic vitreous hemorrhage].

    PubMed

    Conart, J-B; Berrod, J-P

    2016-02-01

    Spontaneous vitreous hemorrhage is a serious disease whose incidence is 7 per 100,000 people per year. Posterior vitreous detachment with or without retinal tear, diabetic retinopathy, vascular proliferation after retinal vein occlusion, age-related macular degeneration and Terson's syndrome are the most common causes. Repeated ultrasonography may ignore a retinal tear or detachment and delay vitrectomy that is the only treatment for serious forms. The occurrence of retinal tear or detachment is a surgical emergency as well as rubeosis or diabetic tractional retinal detachment involving the macula. Intravitreal injection of antiangiogenic agents are helpful in clearing the vitreous cavity, facilitating laser photocoagulation and reducing the risks of bleeding during preretinal neovascular membranes dissection. PMID:26826742

  7. Phenylpropanolamine and cerebral hemorrhage

    SciTech Connect

    McDowell, J.R.; LeBlanc, H.J.

    1985-05-01

    Computerized tomography, carotid angiograms, and arteriography were used to diagnose several cases of cerebral hemorrhage following the use of phenylpropanolamine. The angiographic picture in one of the three cases was similar to that previously described in association with amphetamine abuse and pseudoephedrine overdose, both substances being chemically and pharmacologically similar to phenylpropanolamine. The study suggests that the arterial change responsible for symptoms may be due to spasm rather than arteriopathy. 14 references, 5 figures.

  8. [Spontaneous intraperitoneal hemorrhage: etiology].

    PubMed

    Ksontini, R; Roulet, D; Cosendey, B A; Cavin, R

    2001-10-01

    Spontaneous intraperitoneal hemorrhage is a rare and sometime fatal condition. The clinical presentation may range from a non-specific abdominal pain to an acute abdomen with hemodynamic instability. Often, a preoperative diagnosis cannot be obtained. Immediate surgical exploration remains the treatment of choice. However, pre or postoperative diagnosis can sometime be confirmed and treated with interventional radiology. In rare cases, the site of bleeding remains unknown despite intraoperative exploration and radiographic studies. PMID:11715286

  9. Pre-Transplant Screening for Latent Adenovirus in Donors and Recipients

    PubMed Central

    Piatti, Gabriella

    2016-01-01

    Human adenoviruses are frequent cause of slight self-limiting infections in immune competent subjects, while causing life-threatening and disseminated diseases in immunocompromised patients, particularly in the subjects affected by acquired immunodeficiency syndrome and in bone marrow and organ transplant recipients. Here, infections interest lungs, liver, encephalon, heart, kidney and gastro enteric tract. To date, human adenoviruses comprise 51 serotypes grouped into seven species, among which species C especially possesses the capability to persist in infected tissues. From numerous works, it emerges that in the recipient, because of loss of immune-competence, both primary infection, via the graft or from the environment, and reactivated endogenous viruses can be responsible for transplantation related adenovirus disease. The transplants management should include the evaluation of anti-adenovirus pre-transplant screening similar to that concerning cytomegalovirus. The serological screening on cytomegalovirus immunity is currently performed to prevent viral reactivation from grafts and recipient, the viral spread and dissemination to different organs and apparatus, and potentially lethal outcome. PMID:27006724

  10. Viruses Causing Hemorrhagic Fever. Safety Laboratory Procedures

    PubMed Central

    Cobo, Fernando

    2016-01-01

    Viral hemorrhagic fevers are diseases caused by viruses which belong to different families, many of them causing severe diseases. These viruses may produce different symptomatology together with a severe multisystem syndrome, and the final result might be the production of hemorrhages in several sites of the body. The majority of them have no other treatment than supportive therapy, although some antiviral drugs can be used in some circumstances. Transmission of VHF has been demonstrated through contact with animal vectors or person-to-person through the contact with body fluids. No risk of transmission has been found during the incubation period, but when the viral load is high the risk of transmission is greatest. Both health care and clinical laboratory workers must safely handle patients and specimens by taking all required precautions during their management. PMID:27014378

  11. [Massive bilateral subconjunctival hemorrhage revealing acute lymphoblastic leukemia].

    PubMed

    Taamallah-Malek, I; Chebbi, A; Bouladi, M; Nacef, L; Bouguila, H; Ayed, S

    2013-03-01

    We report the case of 20-year-old patient who presented in emergency with bilateral massive, spontaneous subconjunctival hemorrhage. Clinical findings suggested a blood dyscrasia, which was confirmed by blood cell count. The patient was urgently referred to hematology where the diagnosis of acute lymphoblastic leukemia was made. This case highlights the importance of working up any unusual subconjunctival hemorrhage, as it may reveal, in certain cases, a severe life-threatening disease. PMID:23122838

  12. Characterisation of the Equine adenovirus 2 genome.

    PubMed

    Giles, Carla; Vanniasinkam, Thiru; Barton, Mary; Mahony, Timothy J

    2015-09-30

    Equine adenovirus 2 (EAdV-2) is one of two serotypes of adenoviruses known to infect equines. Initial studies did not associate EAdV-2 infections with any specific clinical syndromes, although more recent evidence suggests that EAdV-2 may be associated with clinical and subclinical gastrointestinal infections of foals and adults respectively. In contrast, Equine adenovirus 1 is well recognised as a pathogen associated with upper respiratory tract infections of horses. In this study the complete genome sequence of EAdV-2 is reported. As expected, genes common to the adenoviruses were identified. Phylogenetic reconstructions using selected EAdV-2 genes confirmed the classification of this virus within the Mastadenovirus genus, and supported the hypothesis that EAdV-2 and EAdV-1 have evolved from separate lineages within the adenoviruses. One spliced open reading frame was identified that encoded for a polypeptide with high similarity to the pIX and E1b_55K adenovirus homologues and was designated pIX_E1b_55K. In addition to this fused version of E1b_55K, a separate E1b_55K encoding gene was also identified. These polypeptides do not appear to have evolved from a gene duplication event as the fused and unfused E1b_55K were most similar to E1b_55K homologues from the Atadenovirus and Mastadenovirus genera respectively. The results of this study suggest that EAdV-2 has an unusual evolutionary history that warrants further investigation. PMID:26220513

  13. Advances in fluid resuscitation of hemorrhagic shock

    PubMed Central

    Tremblay, Lorraine N.; Rizoli, Sandro B.; Brenneman, Frederick D.

    2001-01-01

    The optimal fluid for resuscitation in hemorrhagic shock would combine the volume expansion and oxygen-carrying capacity of blood without the need for cross-matching or the risk of disease transmission. Although the ideal fluid has yet to be discovered, current options are discussed in this review, including crystalloids, colloids, blood and blood substitutes. The future role of blood substitutes is not yet defined, but the potential advantages in trauma or elective surgery may prove to be enormous. PMID:11407826

  14. Molecular Epidemiology and Clinical Manifestations of Adenovirus Respiratory Infections in Taiwanese Children

    PubMed Central

    Wang, Ya-Fang; Shen, Fan-Ching; Wang, Shan-Li; Kuo, Pin-Hwa; Tsai, Huey-Pin; Liu, Ching-Chuan; Wang, Jen-Ren; Chi, Chia-Yu

    2016-01-01

    Abstract Human adenoviruses (HAdVs) are important causes of respiratory infections in children. They usually cause mild upper respiratory symptoms, but they can also produce severe pneumonia and other complications. The aims of this retrospective study were to better define the molecular epidemiology of respiratory adenoviruses circulating in Taiwanese children during 2002 and 2013, detect reinfections and co-infections, and characterize the clinical features and laboratory findings according to the causative genotypes. We collected a representative sample of 182 isolates of adenoviruses from 175 children during the 12-year study period. The most prevalent species was HAdV-B genotype 3 (HAdV-3) (92/182, 50.5%) followed by HAdV-C (HAdV-2) (38/182, 20.9%). A single outbreak of HAdV-E (6/182, 3.3%) was noted in 2007. The mean age of children with adenovirus infections was 3.7 ± 2.0 years, with a slight predominance of males (53.1%). Children with HAdV-B tended to be older, had more lower respiratory tract infections, gastrointestinal symptoms, and a higher rate of hospitalization than those with HAdV-C (P < 0.05). Adenovirus co-infections were noted in 25/175 (14.3%) of the children. The most frequent co-infections were with species B (HAdV-3) and C (HAdV-2) (14/25, 56.0%). Additional infections were noted in 23/175 (13.1%) of the children. Of these repeated infections, the initial isolates were always genotypes of HAdV-C. The second isolates were genotypes of HAdV-B or HAdV-E. The clinical features of the first HAdV-B infection and the reinfection of HAdV-B followed the HAdV-C were similar. In conclusion, HAdV-B, C, and E were the only adenovirus species that were isolated from children who were sufficiently ill with respiratory infections to require a visit to the hospital. Human adenovirus B (HAdV-3) accounted for half of these species. HAdV-B was more likely than other species to produce severe disease. The high incidence of adenovirus co-infection and

  15. [Hemorrhagic stroke associated to neurocysticercosis].

    PubMed

    Tellez-Zenteno, J F; Negrete-Pulido, O; Cantú, C; Márquez, C; Vega-Boada, F; García Ramos, G

    2003-06-01

    A well-known complication of neurocysticercosis is cerebral arteritis, which is usually manifested by cerebral ischemia. Only anecdotal cases of hemorrhagic stroke associated to this parasitosis have been described. Previously there are only two reported cases of this association. One of these cases had an intracystic hemorrhage confirmed by autopsy without cerebrovascular risk factors. Autopsy revealed an inflammatory arteriopathy adjacent to the cyst intracystic hemorrhage. The second case had a subarachnoidal hemorrhage secondary to the rupture of an aneurysm in the right anteroinferior cerebellar artery. At surgery, the aneurysm was found to be surrounded by a thickened-leptomeninges, which histologically showed the presence of cysticercous with dense inflammation. Our first patient was a 32 year-old female developed a lenticulo-capsular hemorrhage around a cysticercotic lesion. The second patient was a 34 year-old male developed an intracystic hemorrhage. As cerebral angiography was normal in both patients, cerebral hemorrhages were considered to be related to cysticercotic arteritis of small penetrating vessels. We conclude that cysticercosis is associated with differenttypes of intracranial hemorrhage, as documented the present cases. In neurocysticercosis endemic areas, cysticercotic arteritis should be added to the list of causes of intracranial hemorrhage in young people. PMID:12768515

  16. Characteristics of Noncultivable Adenoviruses Associated with Diarrhea in Infants: A New Subgroup of Human Adenoviruses

    PubMed Central

    Gary, G. William; Hierholzer, John C.; Black, Robert E.

    1979-01-01

    Virus particles morphologically resembling adenovirus were found in fecal specimens from infants and were examined for cultivability with standard cell culture techniques and for characteristics of human adenoviruses. Specimens from 13 of 15 infants could not be cultivated in cell cultures. The two adenoviruses that were cultivated, types 1 and 31, reacted in the expected manner in all tests. Counterimmunoelectrophoresis with group-specific anti-hexon serum confirmed that the observed particles in the 15 specimens were human adenoviruses. The buoyant density in sucrose of five of the noncultivable adenoviruses in original stool suspensions averaged 1.335 g/cm3 and that of the two cultivable ones averaged 1.332 g/cm3; both groups had typical adenovirus morphology by electron microscopy. Treatment of the specimens and of a variety of tissue culture cells with proteolytic and other enzymes did not improve cultivability. Examination of partially purified virus by immunoelectron microscopy did not reveal evidence of immunoglobulin A, G, or M coating on the particles, an indication that coproantibody inhibition was not the cause of noncultivability. Fluorescent-antibody studies with an antihexon conjugate and counterimmunoelectrophoresis studies of serially passaged noncultivable viruses indicated that the viruses are infecting cells but are not undergoing effective replication. Antisera to three of the noncultivable viruses demonstrated homologous reactions in counterimmunoelectrophoresis with the respective immunizing antigens but showed only low levels of hemagglutination-inhibiting and neutralizing activity to a few of the known human adenoviruses. We concluded that the noncultivable viruses in these infant diarrhea cases were indeed human adenoviruses, were not defective particles, were not bound to coproantibody, were infectious but incapable of effective relication in conventional cell cultures, were serologically related to types 11, 17, 32, and 33, and should be

  17. Adenovirus vaccine vectors expressing hepatitis B surface antigen: importance of regulatory elements in the adenovirus major late intron.

    PubMed

    Mason, B B; Davis, A R; Bhat, B M; Chengalvala, M; Lubeck, M D; Zandle, G; Kostek, B; Cholodofsky, S; Dheer, S; Molnar-Kimber, K

    1990-08-01

    Adenovirus types 4 and 7 are currently used as live oral vaccines for prevention of acute respiratory disease caused by these adenovirus serotypes. To investigate the concept of producing live recombinant vaccines using these serotypes, adenovirus types 4 (Ad4) and 7 (Ad7) were constructed that produce HBsAg upon infection of cell cultures. Ad4 recombinants were constructed that express HBsAg from a cassette inserted 135 bp from the right-hand terminus of the viral genome. The cassette contained the Ad4 major late promoter followed by leader 1 of the tripartite leader, the first intervening sequence between leaders 1 and 2, leaders 2 and 3, the HBsAg gene, and tandem polyadenylation signals from the Ad4 E3B and hexon genes. Using this same cassette, a series of Ad4 recombinants expressing HBsAg were constructed with deletions in the intervening sequence between leaders 1 and 2 to evaluate the contribution of the downstream control elements more precisely. Inclusion of regions located between +82 and +148 as well as +148 and +232 resulted in increases in expression levels of HBsAg in A549-infected cells by 22-fold and 44-fold, respectively, over the levels attained by an adenovirus recombinant retaining only sequences from +1 to +82, showing the importance of these elements in the activation of the major late promoter during the course of a natural Ad4 viral infection. Parallel increases were also observed in steady-state levels of cytoplasmic HBsAg-specific mRNA. When similar Ad7 recombinant viruses were constructed, these viruses also expressed 20-fold more HBsAg due to the presence of the intron. All Ad4 and Ad7 recombinants produced HBsAg particles containing gp27 and p24 which were secreted in the medium. When dogs were immunized intratracheally with one of these Ad7 recombinants, they seroconverted to both Ad7 and HBsAg to a high level. PMID:2371766

  18. Adrenal dysfunction in portal hypertensive rats with acute hemorrhage.

    PubMed

    Lee, Fa-Yauh; Wang, Sun-Sang; Tsai, Ming-Hung; Huang, Hui-Chun; Lin, Han-Chieh; Lee, Shou-Dong

    2014-01-01

    Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the 'hepatoadrenal syndrome', but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down

  19. Adrenal Dysfunction in Portal Hypertensive Rats with Acute Hemorrhage

    PubMed Central

    Lee, Fa-Yauh; Wang, Sun-Sang; Lin, Han-Chieh; Lee, Shou-Dong

    2014-01-01

    Nitric oxide (NO) participates in shock and poorer portal hypotensive effect to vasoconstrictors in portal hypertension with hemorrhage, the so-called splanchnic hyposensitivity. Relative adrenal insufficiency accompanies hemorrhagic shock and is found in liver disease, the ‘hepatoadrenal syndrome’, but the relevant interactions remain unsettled. Portal hypertensive rats were induced by partial portal vein ligation (PVL). Experiments were performed on the 14th day post PVL: (I) ACTH stimulation test for rats without or with hemorrhage; (II) Glypressin response (mean arterial pressure, MAP; portal pressure, PP) in rats (a) without hemorrhage or with hemorrhage, injected with (b) distilled water (DW), (c) dexamethasone 3 mg/kg; (III) To survey the dose-dependent effects of glucocorticoid without being confounded by endogenous adrenal hormone, glypressin response was surveyed in PVL rats with adrenalectomy: (a) without hemorrhage or with hemorrhage, injected with (b) DW; (c) dexamethasone 3 mg/kg; (d) dexamethasone 5 mg/kg. Plasma tumor necrosis factor-α (TNF-α) concentrations and abdominal aorta (AA), superior mesenteric artery (SMA) NO synthases (NOS) mRNA expressions were determined. The results showed that ACTH induced corticosterone release similarly in PVL rats with or without hemorrhage. In bleeding PVL rats, dexamethasone (1) down-regulated AA NOS and enhanced glypressin-induced MAP elevation; (2) did not influence glypressin-induced PP reduction; (3) reduced TNF-α. In bleeding PVL and adrenalectomized rats, high-dose dexamethasone (1) down-regulated AA/SMA NOS; (2) enhanced glypressin-induced MAP elevation and PP reduction; (3) reduced TNF-α. In conclusion, bleeding portal hypertensive rats failed to enhance corticosterone release, suggesting a relative adrenal insufficiency. High-dose dexamethasone reversed systemic hypotension and splanchnic hyporesponsiveness to glypressin in adrenalectomized PVL rats accompanied by TNF-α and NOS down

  20. A novel psittacine adenovirus identified during an outbreak of avian chlamydiosis and human psittacosis: zoonosis associated with virus-bacterium coinfection in birds.

    PubMed

    To, Kelvin K W; Tse, Herman; Chan, Wan-Mui; Choi, Garnet K Y; Zhang, Anna J X; Sridhar, Siddharth; Wong, Sally C Y; Chan, Jasper F W; Chan, Andy S F; Woo, Patrick C Y; Lau, Susanna K P; Lo, Janice Y C; Chan, Kwok-Hung; Cheng, Vincent C C; Yuen, Kwok-Yung

    2014-12-01

    Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs) with sequence similarity to known adenoviral genes, and six additional ORFs at the 3' end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3-54.0% for the DNA polymerase, 64.6-70.7% for the penton protein, and 66.1-74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention and should be

  1. A Novel Psittacine Adenovirus Identified During an Outbreak of Avian Chlamydiosis and Human Psittacosis: Zoonosis Associated with Virus-Bacterium Coinfection in Birds

    PubMed Central

    Chan, Wan-Mui; Choi, Garnet K. Y.; Zhang, Anna J. X.; Sridhar, Siddharth; Wong, Sally C. Y.; Chan, Jasper F. W.; Chan, Andy S. F.; Woo, Patrick C. Y.; Lau, Susanna K. P.; Lo, Janice Y. C.; Chan, Kwok-Hung; Cheng, Vincent C. C.; Yuen, Kwok-Yung

    2014-01-01

    Chlamydophila psittaci is found worldwide, but is particularly common among psittacine birds in tropical and subtropical regions. While investigating a human psittacosis outbreak that was associated with avian chlamydiosis in Hong Kong, we identified a novel adenovirus in epidemiologically linked Mealy Parrots, which was not present in healthy birds unrelated to the outbreak or in other animals. The novel adenovirus (tentatively named Psittacine adenovirus HKU1) was most closely related to Duck adenovirus A in the Atadenovirus genus. Sequencing showed that the Psittacine adenovirus HKU1 genome consists of 31,735 nucleotides. Comparative genome analysis showed that the Psittacine adenovirus HKU1 genome contains 23 open reading frames (ORFs) with sequence similarity to known adenoviral genes, and six additional ORFs at the 3′ end of the genome. Similar to Duck adenovirus A, the novel adenovirus lacks LH1, LH2 and LH3, which distinguishes it from other viruses in the Atadenovirus genus. Notably, fiber-2 protein, which is present in Aviadenovirus but not Atadenovirus, is also present in Psittacine adenovirus HKU1. Psittacine adenovirus HKU1 had pairwise amino acid sequence identities of 50.3–54.0% for the DNA polymerase, 64.6–70.7% for the penton protein, and 66.1–74.0% for the hexon protein with other Atadenovirus. The C. psittaci bacterial load was positively correlated with adenovirus viral load in the lung. Immunostaining for fiber protein expression was positive in lung and liver tissue cells of affected parrots, confirming active viral replication. No other viruses were found. This is the first documentation of an adenovirus-C. psittaci co-infection in an avian species that was associated with a human outbreak of psittacosis. Viral-bacterial co-infection often increases disease severity in both humans and animals. The role of viral-bacterial co-infection in animal-to-human transmission of infectious agents has not received sufficient attention and should

  2. Hemorrhagic radiation cystitis.

    PubMed

    Mendenhall, William M; Henderson, Randal H; Costa, Joseph A; Hoppe, Bradford S; Dagan, Roi; Bryant, Curtis M; Nichols, Romaine C; Williams, Christopher R; Harris, Stephanie E; Mendenhall, Nancy P

    2015-06-01

    The optimal management of persistent hemorrhagic radiation cystitis is ill-defined. Various options are available and include oral agents (ie, sodium pentosan polysulfate), intravenous drugs (ie, WF10), topical agents (ie, formalin), hyperbaric oxygen, and endoscopic procedures (ie, electrical cautery, argon plasma coagulation, laser coagulation). In general, it is best to manage patients conservatively and intervene only when necessary with the option least likely to exacerbate the cystitis. More aggressive measures should be employed only when more conservative approaches fail. Bladder biopsies should be avoided, unless findings suggest a bladder tumor, because they may precipitate a complication. PMID:24322335

  3. Structure and Uncoating of Immature Adenovirus

    SciTech Connect

    Perez-Berna, A.J.; Mangel, W.; Marabini, R.; Scheres, S. H. W., Menendez-Conejero, R.; Dmitriev, I. P.; Curiel, D. T.; Flint, S. J.; San Martin, C.

    2009-09-18

    Maturation via proteolytic processing is a common trait in the viral world and is often accompanied by large conformational changes and rearrangements in the capsid. The adenovirus protease has been shown to play a dual role in the viral infectious cycle: (a) in maturation, as viral assembly starts with precursors to several of the structural proteins but ends with proteolytically processed versions in the mature virion, and (b) in entry, because protease-impaired viruses have difficulties in endosome escape and uncoating. Indeed, viruses that have not undergone proteolytic processing are not infectious. We studied the three-dimensional structure of immature adenovirus particles as represented by the adenovirus type 2 thermosensitive mutant ts1 grown under non-permissive conditions and compared it with the mature capsid. Our three-dimensional electron microscopy maps at subnanometer resolution indicate that adenovirus maturation does not involve large-scale conformational changes in the capsid. Difference maps reveal the locations of unprocessed peptides pIIIa and pVI and help define their role in capsid assembly and maturation. An intriguing difference appears in the core, indicating a more compact organization and increased stability of the immature cores. We have further investigated these properties by in vitro disassembly assays. Fluorescence and electron microscopy experiments reveal differences in the stability and uncoating of immature viruses, both at the capsid and core levels, as well as disassembly intermediates not previously imaged.

  4. Rapid generation of fowl adenovirus 9 vectors.

    PubMed

    Pei, Yanlong; Griffin, Bryan; de Jong, Jondavid; Krell, Peter J; Nagy, Éva

    2015-10-01

    Fowl adenoviruses (FAdV) have the largest genomes of any fully sequenced adenovirus genome, and are widely considered as excellent platforms for vaccine development and gene therapy. As such, there is a strong need for stream-lined protocols/strategies for the generation of recombinant adenovirus genomes. Current genome engineering strategies rely upon plasmid based homologous recombination in Escherichia coli BJ5183. This process is time-consuming, involves multiple cloning steps, and low efficiency recombination. This report describes a novel system for the more rapid generation of recombinant fowl adenovirus genomes using the lambda Red recombinase system in E. coli DH10B. In this strategy, PCR based amplicons with around 50 nt long homologous arms, a unique SwaI site and a chloramphenicol resistance gene fragment (CAT cassette), are introduced into the FAdV-9 genome in a highly efficient and site-specific manner. To demonstrate the efficacy of this system we generated FAdV-9 ORF2, and FAdV-9 ORF11 deleted, CAT marked and unmarked FAdV-9 infectious clones (FAdmids), and replaced either ORF2 or ORF11, with an EGFP expression cassette or replaced ORF2 with an EGFP coding sequence via the unique SwaI sites, in approximately one month. All recombinant FAdmids expressed EGFP and were fully infectious in CH-SAH cells. PMID:26238923

  5. Intracranial hemorrhage in cancer patients treated with anticoagulation.

    PubMed

    Weinstock, Matthew J; Uhlmann, Erik J; Zwicker, Jeffrey I

    2016-04-01

    Both venous thromboembolism and intracranial metastases are common complications in the setting of primary brain tumors and metastatic malignancies. Anticoagulation is indicated in the presence of cancer-associated thrombosis in order to limit the risk of pulmonary embolism; however, there is reluctance to initiate anticoagulation in the setting of intracranial metastatic disease due to potential for intracranial hemorrhage. Recent evidence suggests that therapeutic anticoagulation can be safely administered in the setting of metastatic brain tumors. This review examines the current understanding of the pathophysiology of intracranial hemorrhage in malignancy, describes the incidence of intracranial hemorrhage in the setting of brain tumors with therapeutic anticoagulation, and outlines management strategies relevant to the treatment of intracranial hemorrhage in the setting of anticoagulation. PMID:27067980

  6. Lethal Hemorrhage Caused by Aortoenteric Fistula Following Endovascular Stent Implantation

    SciTech Connect

    Kahlke, Volker; Brossmann, Joachim; Klomp, Hans-Juergen

    2002-06-15

    A 55-year-old women developed an aortointestinal fistula between the bifurcation of the aorta and the distal ileum following implantation of multiple endovascular stents into both common iliac arteries for treatment of aortoiliac occlusive disease. Ten months before the acute onset of the gastrointestinal hemorrhage two balloon-expandable steel stents had been implanted into both common iliac arteries. Due to restenosis and recurrent intermittent claudication, three balloon-expandable covered stents were implanted 4 months later on reintervention. The patient presented with abdominal pain and melena, and fell into hemorrhagic shock with signs of upper gastrointestinal bleeding. After transfer to our hospital, she again developed hemorrhagic shock with massive upper and lower gastrointestinal bleeding and died during emergency laparotomy. The development of aortoenteric fistulas following endovascular surgery/stent implantation is very rare and has to be considered in cases of acute gastrointestinal hemorrhage.

  7. Prenatal diagnosis of fetal adrenal hemorrhage and endocrinologic evaluation

    PubMed Central

    Shin, Se In; Yoo, Ji Geun; Park, In Yang

    2016-01-01

    We present a case of a fetal adrenal hemorrhage, a rare disease in fetal life, detected prenatally at 36 weeks' gestation by ultrasound. Routine ultrasound examination at 36 weeks' gestation by primary obstetrician showed a cyst on the fetal suprarenal area. Initially, the suspected diagnosis was a fetal adrenal hemorrhage, but we should diagnose differently from neuroblastoma. Subsequent ultrasound examination at 38 and 39 weeks' gestation showed increase of the cyst in size. A 3.34-kg-male neonate was born by spontaneous vaginal delivery at 39 weeks' gestation. The diagnosis of adrenal hemorrhage was confirmed by postnatal follow-up sonograms and magnetic resonance imaging. Course and sonographic signs were typical for adrenal hemorrhage and the neonate was therefore managed without surgical exploration. PMID:27200316

  8. Immunologic hemorrhagic pneumonia caused by isocyanates.

    PubMed

    Patterson, R; Nugent, K M; Harris, K E; Eberle, M E

    1990-01-01

    The occurrence of hemoptysis, dyspnea, and bilateral pulmonary opacities progressed to respiratory failure in a 34-yr-old man. Recovery occurred with corticosteroid therapy. In the absence of evidence for an infectious etiology, the possibility of immunologic trimellitic anhydride (TMA) hemorrhagic pneumonitis was considered when the lung biopsy excluded Goodpasture's and other diseases and because the patient was a spray painter. Serologic evaluation for antibodies against TMA was requested. Because the immunologic studies for TMA were negative, and because the patient was a spray painter, immunoassays for three isocyanates conjugated to human serum albumin (HSA) were carried out although there was no specific history of isocyanate exposure at that time. High levels of IgG and IgE antibodies were detected against hexamethylene diisocyanate (HDI)-HSA and toluene diisocyanate (TDI)-HSA. Further investigation documented exposure to spray paint that contained HDI and another isocyanate. The paint was sprayed on warm metal, and subsequently the worker developed an acute illness. Further plant studies were not possible. We propose that the pathogenesis of this case of hemorrhagic pneumonitis is immunologic because of uncontrolled exposure to HDI and TDI, is analogous to the immunologic hemorrhagic pneumonia caused by TMA, and should be considered as a possible cause of a similar acute lung disease after isocyanate exposure. PMID:2153356

  9. Fluorescent antibody responses to adenoviruses in humans.

    PubMed Central

    Ariyawansa, J P; Tobin, J O

    1976-01-01

    Specific IgG, IgA, and IgM immunoglobulin antibody responses to adenovirus infections were studied by the indirect immunofluorescent technique in six pairs of human sera obtained during acute and convalescent phases of the illness. In addition, 70 single specimens of sera showing adenovirus IgG antibody from different age groups from birth to the 60th year of life were titrated for the same antibody to adenovirus types 1, 2, 3, 5, and 7, and 170 serum specimens from the same age groups were screened for specific immunoglobulin antibodies against types 1 and 5. Specific immunoglobulin antibodies lacked type specificity and in acute infections measured heterologous antibody response as well. On the other hand, IgG antibodies detected in single specimens of sera by immunofluorescence correlate with surveys of the isolation of virus from patients and neutralizing antibody studies by other workers. Fluorescent antibodies appeared in all three fractions of the immunoglobulins in acute adenovirus infections. Although this technique may be used in the diagnosis of adenovirus infections there is no advantage compared to complement-fixation testing. However, the use of sera absorbed with group antigen may have a more useful place in serological epidemiology than in diagnostic work. In five pairs of sera obtained during acute and convalescent phases of adenoviral illness and in 70 random single specimens from different age groups, "T" antibodies were detected only in the IgG fraction. The paired sera did not show a significant rise to indicate the usefulness of "T" antibody study in diagnosis. PMID:180061

  10. Fluorescent antibody responses to adenoviruses in humans.

    PubMed

    Ariyawansa, J P; Tobin, J O

    1976-05-01

    Specific IgG, IgA, and IgM immunoglobulin antibody responses to adenovirus infections were studied by the indirect immunofluorescent technique in six pairs of human sera obtained during acute and convalescent phases of the illness. In addition, 70 single specimens of sera showing adenovirus IgG antibody from different age groups from birth to the 60th year of life were titrated for the same antibody to adenovirus types 1, 2, 3, 5, and 7, and 170 serum specimens from the same age groups were screened for specific immunoglobulin antibodies against types 1 and 5. Specific immunoglobulin antibodies lacked type specificity and in acute infections measured heterologous antibody response as well. On the other hand, IgG antibodies detected in single specimens of sera by immunofluorescence correlate with surveys of the isolation of virus from patients and neutralizing antibody studies by other workers. Fluorescent antibodies appeared in all three fractions of the immunoglobulins in acute adenovirus infections. Although this technique may be used in the diagnosis of adenovirus infections there is no advantage compared to complement-fixation testing. However, the use of sera absorbed with group antigen may have a more useful place in serological epidemiology than in diagnostic work. In five pairs of sera obtained during acute and convalescent phases of adenoviral illness and in 70 random single specimens from different age groups, "T" antibodies were detected only in the IgG fraction. The paired sera did not show a significant rise to indicate the usefulness of "T" antibody study in diagnosis. PMID:180061

  11. Labeling of Adenovirus Particles with PARACEST Agents

    PubMed Central

    Vasalatiy, Olga; Gerard, Robert D; Zhao, Piyu; Sun, Xiankai; Sherry, A. Dean

    2009-01-01

    Recombinant adenovirus type 5 particles (AdCMVLuc) were labeled with two different bifunctional ligands capable of forming stable complexes with paramagnetic lanthanide ions. The number of covalently attached ligands varied between 630 and 1960 per adenovirus particle depending upon the chemical reactivity of the bifunctional ligand (NHS ester versus isothiocyanide), the amount of excess ligand added, and the reaction time. The bioactivity of each labeled adenovirus derivative, as measured by the ability of the virus to infect cells and express luciferase, was shown to be highly dependent upon the number of covalently attached ligands. This indicates that certain amino groups, likely on the surface of the adenovirus fiber protein where cell binding is known to occur, are critical for viral attachment and infection. Addition of 177Lu3+ to chemically modified versus control viruses demonstrated a significant amount of nonspecific binding of 177Lu3+ to the virus particles that could not be sequestered by addition of excess DTPA. Thus, it became necessary to implement a prelabeling strategy for conjugation of preformed lanthanide ligand chelates to adenovirus particles. Using preformed Tm3+-L2, a large number of chelates having chemical exchange saturation transfer (CEST) properties were attached to the surface residues of AdCMVLuc without nonspecific binding of metal ions elsewhere on the virus particle. The potential of such conjugates to act as PARACEST imaging agents was tested using an on-resonance WALTZ sequence for CEST activation. A 12% decrease in bulk water signal intensity was observed relative to controls. This demonstrates that viral particles labeled with PARACEST-type imaging agents can potentially serve as targeted agents for molecular imaging. PMID:18254605

  12. Acute hemorrhagic leukoencephalitis with atypical features.

    PubMed

    Catalan, Mauro; Naccarato, Marcello; Grandi, Fabio Chiodo; Capozzoli, Francesca; Koscica, Nadia; Pizzolato, Gilberto

    2009-02-01

    Acute hemorrhagic leukoencephalitis (AHL) is a rare demyelinating disease mainly affecting children, characterized by acute onset, progressive course and high mortality. A 62-year-old man was admitted to our Unit for diplopia and ataxia ensuing 2 weeks after the onset of pneumonia. MRI T2-weighted images showed signal hyperintensities in the brainstem. Antibodies against Mycoplasma Pneumoniae and cold agglutinins were found. Two weeks later the patient had a worsening of his conditions: he developed left hemiplegia with motor focal seizures and the day after he was deeply comatose (GCS = 4). A second MRI scan showed extensive hyperintensities involving the whole right hemisphere white matter with a small parietal hemorrhagic area. The clinical and neuroimaging features suggested the diagnosis of AHL, Aciclovir in association with steroid therapy were administered and then plasmapheresis was started. After 30 days of coma, the patient gradually reacquired consciousness and motor functions; anyway a left hemiplegia persisted. PMID:19145402

  13. Elephant Endotheliotropic Herpesviruses EEHV1A, EEHV1B, and EEHV2 from Cases of Hemorrhagic Disease Are Highly Diverged from Other Mammalian Herpesviruses and May Form a New Subfamily

    PubMed Central

    Richman, Laura K.; Zong, Jian-Chao; Latimer, Erin M.; Lock, Justin; Fleischer, Robert C.; Heaggans, Sarah Y.

    2014-01-01

    ABSTRACT A family of novel endotheliotropic herpesviruses (EEHVs) assigned to the genus Proboscivirus have been identified as the cause of fatal hemorrhagic disease in 70 young Asian elephants worldwide. Although EEHV cannot be grown in cell culture, we have determined a total of 378 kb of viral genomic DNA sequence directly from clinical tissue samples from six lethal cases and two survivors. Overall, the data obtained encompass 57 genes, including orthologues of 32 core genes common to all herpesviruses, 14 genes found in some other herpesviruses, plus 10 novel genes, including a single large putative transcriptional regulatory protein (ORF-L). On the basis of differences in gene content and organization plus phylogenetic analyses of conserved core proteins that have just 20% to 50% or less identity to orthologues in other herpesviruses, we propose that EEHV1A, EEHV1B, and EEHV2 could be considered a new Deltaherpesvirinae subfamily of mammalian herpesviruses that evolved as an intermediate branch between the Betaherpesvirinae and Gammaherpesvirinae. Unlike cytomegaloviruses, EEHV genomes encode ribonucleotide kinase B subunit (RRB), thymidine kinase (TK), and UL9-like origin binding protein (OBP) proteins and have an alphaherpesvirus-like dyad symmetry Ori-Lyt domain. They also differ from all known betaherpesviruses by having a 40-kb large-scale inversion of core gene blocks I, II, and III. EEHV1 and EEHV2 DNA differ uniformly by more than 25%, but EEHV1 clusters into two major subgroups designated EEHV1A and EEHV1B with ancient partially chimeric features. Whereas large segments are nearly identical, three nonadjacent loci totaling 15 kb diverge by between 21 and 37%. One strain of EEHV1B analyzed is interpreted to be a modern partial recombinant with EEHV1A. IMPORTANCE Asian elephants are an endangered species whose survival is under extreme pressure in wild range countries and whose captive breeding populations in zoos are not self-sustaining. In 1999, a

  14. Analysis of subconjunctival hemorrhage

    PubMed Central

    Sahinoglu-Keskek, Nedime; Cevher, Selim; Ergin, Ahmet

    2013-01-01

    Objective: To determine associated conditions, gender distribution and location of subconjunctival hemorrhage (SCH). Methodology: This retrospective, observational and non-interventional study involved total of 50 patients with SCH aged 0.16-88 years. The conjunctiva was divided into 4 equal areas. The data about the subjects with SCH that includes age, gender, medical history, ocular history and location of hemorrhage were noted for all patients. Results: The patients with SCH consisted of 21 (42%) women and 29 (58%) men, with a mean age of 29.56 years. Of the 50 patients, 34 (68%) had traumatic and 16 (32%) had spontaneous SCH. Of traumatic SCH group 24 (70.6%) were men and 10 (29.4%) were women. SCH was more common in the temporal areas than other areas (40.5%). Conclusion: The most associated condition in spontaneous SCH was hypertension. SCH was found to be predominant in the temporal areas among all patients. In traumatic SCH, temporal areas were affected more, whereas in spontaneous SCH, nasal and temporal areas were affected equally. Traumatic etiology was more likely seen in men than women. PMID:24353524

  15. Update on exercise-induced pulmonary hemorrhage.

    PubMed

    Sullivan, Stacey; Hinchcliff, Kenneth

    2015-04-01

    Exercise-induced pulmonary hemorrhage (EIPH) is an important disease of horses that perform high-intensity athletic activity. EIPH is an ongoing concern for the racing industry because of its high prevalence; potential impact on performance; welfare concerns; and use of prophylactic medications, such as furosemide, on race day. During the last 10 years, significant progress has been made in understanding the pathogenesis and risk factors for EIPH and the impact of the disease on performance and career. This article summarizes the most recent advances in EIPH. PMID:25770069

  16. The outcome of prophylactic intravenous cefazolin and ceftriaxone in cirrhotic patients at different clinical stages of disease after endoscopic interventions for acute variceal hemorrhage.

    PubMed

    Wu, Cheng-Kun; Wang, Jing-Houng; Lee, Chen-Hsiang; Wu, Keng-Liang; Tai, Wei-Chen; Lu, Sheng-Nan; Hu, Tsung-Hui; Chuah, Seng-Kee

    2013-01-01

    Antibiotic prophylaxis with norfloxacin, intravenous ciprofloxacin, or ceftriaxone has been recommended for cirrhotic patients with gastrointestinal hemorrhage but little is known about intravenous cefazolin. This study aimed to compare the outcome of intravenous cefazolin and ceftriaxone as prophylactic antibiotics among cirrhotic patients at different clinical stages, and to identify the associated risk factors. The medical records of 713 patients with acute variceal bleeding who had received endoscopic procedures from were reviewed. Three hundred and eleven patients were entered for age-matched adjustment after strict exclusion criteria. After the adjustment, a total of 102 patients were enrolled and sorted into 2 groups according to the severity of cirrhosis: group A (Child's A patients, n = 51) and group B (Child's B and C patients, n = 51). The outcomes were prevention of infection, time of rebleeding, and death. Our subgroup analysis results failed to show a significant difference in infection prevention between patients who received prophylactic cefazolin and those who received ceftriaxone among Child's A patients (93.1% vs. 90.9%, p = 0.641); however, a trend of significance in favor of ceftriaxone prophylaxis (77.8% vs. 87.5%, p = 0.072) was seen among Child's B and C patients. More rebleeding cases were observed in patients who received cefazolin than in those who received ceftriaxone among Child's B and C patients (66.7% vs. 25.0%, p = 0.011) but not in Child's A patients (32% vs. 40.9%, p = 0.376). The risk factors associated with rebleeding were history of bleeding and use of prophylactic cefazolin among Child's B and C patients. In conclusion, this study suggests that prophylactic intravenous cefazolin may not be inferior to ceftriaxone in preventing infections and reducing rebleeding among Child's A cirrhotic patients after endoscopic interventions for acute variceal bleeding. Prophylactic intravenous ceftriaxone yields

  17. Glomerular deposition of immune complexes in dogs following natural infection with canine adenovirus.

    PubMed

    Morrison, W I; Nash, A S; Wright, N G

    1975-06-14

    The renal lesions were studied in eight dogs which had either died as a result of acute canine adenovirus infection (Rubarth's disease) or were in various stages of recovery from the clinical disease. Using immunofluorescence techniques granular deposits of IgG were detected in the glomeruli of six dogs; four of these animals had similar glomerular deposits of canine adenovirus antigen. Eluates obtained from kidney tissue of four dogs were found to contain antiviral antibody. Histologically those animals in which glomerular deposits of IgG and viral antigen were detected showed segmental glomerular hypercellularity. These findings were attributed to the deposition of circulating virus antigen-antibody complexes in the glomeruli. PMID:166480

  18. Adenovirus-like inclusion body hepatitis in a flock of broiler chickens in Kermanshah province, Iran

    PubMed Central

    Rahimi, Morad; Minoosh Siavosh Haghighi, Zahra

    2015-01-01

    Inclusion body hepatitis (IBH) has been reported in many countries in the world. The IBH or similar cases characterized by hepatitis and presence of intra-nuclear inclusion bodies in hepatocytes have not been reported in broiler chickens in Iran. This is the first report on outbreak of adenovirus-like inclusion body hepatitis in Iran. On October 2012, an onset of high acute mortality in a flock of 2 day-old broiler chickens was reported to the Veterinary Clinic, Faculty of Veterinary Medicine, Razi University, Kermanshah, Iran. The birds showed lethargy, huddling, ruffled feathers, and inappetence. At necropsy the livers were the primary organ affected which were enlarged, pale yellow with necrotic foci and multiple petechial hemorrhages. Tissue samples of liver, kidneys and heart were fixed in 10% buffered formalin. They were processed and stained with hematoxylin and eosin for histopathological studies. Significant microscopic lesions were seen in the livers. Large eosinophilic intra-nuclear inclusion bodies were seen in hepatocytes. Based on the acute high mortality, age of the broilers, gross lesions and histopathological findings (especially intra-nuclear inclusion bodies), the condition was diagnosed as adenovirus-like inclusion body hepatitis. PMID:25992259

  19. Adenovirus serotype 5 hexon mediates liver gene transfer.

    PubMed

    Waddington, Simon N; McVey, John H; Bhella, David; Parker, Alan L; Barker, Kristeen; Atoda, Hideko; Pink, Rebecca; Buckley, Suzanne M K; Greig, Jenny A; Denby, Laura; Custers, Jerome; Morita, Takashi; Francischetti, Ivo M B; Monteiro, Robson Q; Barouch, Dan H; van Rooijen, Nico; Napoli, Claudio; Havenga, Menzo J E; Nicklin, Stuart A; Baker, Andrew H

    2008-02-01

    Adenoviruses are used extensively as gene transfer agents, both experimentally and clinically. However, targeting of liver cells by adenoviruses compromises their potential efficacy. In cell culture, the adenovirus serotype 5 fiber protein engages the coxsackievirus and adenovirus receptor (CAR) to bind cells. Paradoxically, following intravascular delivery, CAR is not used for liver transduction, implicating alternate pathways. Recently, we demonstrated that coagulation factor (F)X directly binds adenovirus leading to liver infection. Here, we show that FX binds to the Ad5 hexon, not fiber, via an interaction between the FX Gla domain and hypervariable regions of the hexon surface. Binding occurs in multiple human adenovirus serotypes. Liver infection by the FX-Ad5 complex is mediated through a heparin-binding exosite in the FX serine protease domain. This study reveals an unanticipated function for hexon in mediating liver gene transfer in vivo. PMID:18267072

  20. Verapamil Enhances the Antitumoral Efficacy of Oncolytic Adenoviruses

    PubMed Central

    Gros, Alena; Puig, Cristina; Guedan, Sonia; Rojas, Juan José; Alemany, Ramon; Cascallo, Manel

    2010-01-01

    The therapeutic potential of oncolytic adenoviruses is limited by the rate of adenovirus release. Based on the observation that several viruses induce cell death and progeny release by disrupting intracellular calcium homeostasis, we hypothesized that the alteration in intracellular calcium concentration induced by verapamil could improve the rate of virus release and spread, eventually enhancing the antitumoral activity of oncolytic adenoviruses. Our results indicate that verapamil substantially enhanced the release of adenovirus from a variety of cell types resulting in an improved cell-to-cell spread and cytotoxicity. Furthermore, the combination of the systemic administration of an oncolytic adenovirus (ICOVIR-5) with verapamil in vivo greatly improved its antitumoral activity in two different tumor xenograft models without affecting the selectivity of this virus. Overall, our findings indicate that verapamil provides a new, safe, and versatile way to improve the antitumoral potency of oncolytic adenoviruses in the clinical setting. PMID:20179683

  1. Hemorrhage Rates From Brain Arteriovenous Malformation in Hereditary Hemorrhagic Telangiectasia Patients

    PubMed Central

    Kim, Helen; Nelson, Jeffrey; Krings, Timo; terBrugge, Karel G.; McCulloch, Charles E.; Lawton, Michael T.; Young, William L.; Faughnan, Marie E.

    2015-01-01

    Background and Purpose Hereditary hemorrhagic telangiectasia (HHT) is a systemic disease characterized by mucocutaneous telangiectasias, epistaxis, and arteriovenous malformations (AVM). Intracranial hemorrhage (ICH) rates in this population are not well described. We report ICH rates and characteristics in HHT patients with brain arteriovenous malformations (HHT-BAVM). Methods We studied the first 153 HHT-BAVM patients with follow-up data enrolled in the Brain Vascular Malformation Consortium HHT Project. We estimated ICH rates after BAVM diagnosis. Results The majority of patients were female (58%) and Caucasian (98%). The mean age at BAVM diagnosis was 31±19 years (range: 0–70), with 61% of cases diagnosed upon asymptomatic screening. Overall, 14% presented with ICH; among symptomatic cases, 37% presented ruptured. During 493 patient-years of follow-up, 5 ICH events occurred yielding a rate of 1.02% per-year (95% CI: 0.42–2.44%). ICH-free survival differed significantly by ICH presentation (P=0.003); ruptured cases had a higher ICH rate (10.07%, 95% CI: 3.25–31.21%) than unruptured cases (0.43%, 95% CI: 0.11–1.73%). Conclusions HHT-BAVM patients who present with hemorrhage are at a higher risk for re-hemorrhage compared to BAVMs detected pre-symptomatically. PMID:25858236

  2. The Outcome of Prophylactic Intravenous Cefazolin and Ceftriaxone in Cirrhotic Patients at Different Clinical Stages of Disease after Endoscopic Interventions for Acute Variceal Hemorrhage

    PubMed Central

    Wu, Cheng-Kun; Wang, Jing-Houng; Lee, Chen-Hsiang; Wu, Keng-Liang; Tai, Wei-Chen; Lu, Sheng-Nan; Hu, Tsung-Hui; Chuah, Seng-Kee

    2013-01-01

    Antibiotic prophylaxis with norfloxacin, intravenous ciprofloxacin, or ceftriaxone has been recommended for cirrhotic patients with gastrointestinal hemorrhage but little is known about intravenous cefazolin. This study aimed to compare the outcome of intravenous cefazolin and ceftriaxone as prophylactic antibiotics among cirrhotic patients at different clinical stages, and to identify the associated risk factors. The medical records of 713 patients with acute variceal bleeding who had received endoscopic procedures from were reviewed. Three hundred and eleven patients were entered for age-matched adjustment after strict exclusion criteria. After the adjustment, a total of 102 patients were enrolled and sorted into 2 groups according to the severity of cirrhosis: group A (Child’s A patients, n = 51) and group B (Child’s B and C patients, n = 51). The outcomes were prevention of infection, time of rebleeding, and death. Our subgroup analysis results failed to show a significant difference in infection prevention between patients who received prophylactic cefazolin and those who received ceftriaxone among Child’s A patients (93.1% vs. 90.9%, p = 0.641); however, a trend of significance in favor of ceftriaxone prophylaxis (77.8% vs. 87.5%, p = 0.072) was seen among Child’s B and C patients. More rebleeding cases were observed in patients who received cefazolin than in those who received ceftriaxone among Child’s B and C patients (66.7% vs. 25.0%, p = 0.011) but not in Child’s A patients (32% vs. 40.9%, p = 0.376). The risk factors associated with rebleeding were history of bleeding and use of prophylactic cefazolin among Child’s B and C patients. In conclusion, this study suggests that prophylactic intravenous cefazolin may not be inferior to ceftriaxone in preventing infections and reducing rebleeding among Child’s A cirrhotic patients after endoscopic interventions for acute variceal bleeding. Prophylactic intravenous

  3. Intratumoral hemorrhage in a patient with cerebellar hemangioblastoma: a case report and review.

    PubMed

    Wang, Zhen; Hu, Jun; Xu, Liang; Malaguit, Jay; Chen, Sheng

    2015-01-01

    Spontaneous hemorrhage is rarely associated with hemangioblastomas. Intratumoral hemorrhage occurring in cerebellar hemangioblastomas is more rare. A 25-year-old man was admitted to our hospital with headache. We found a round cystic lesion with solid part in the right cerebellum. The lesion was resected. The final pathological diagnosis was hemangioblastomas. The radiological features of this case were similar to normal hemangioblastomas, whereas our histological examination showed the occurrence of the intratumoral hemorrhage. If the hemangioblastoma ruptures in our case, the outcome of the patient will be worse. It is difficult to identify the intratumoral hemorrhage of hemangioblastomas and quite dangerous if it is diagnosed late. Diagnosing an intratumoral hemorrhage of hemangioblastomas still needs a further discussion. Genetic screening may help us make an early diagnosis. Furthermore, the mechanism about intratumoral hemorrhage of hemangioblastomas remains unknown. The mutation of D6Mit135 gene on chromosome 6 may be responsible for the vascular dilation and hemorrhage induction in the hemangioblastomas. Tumor size, upregulation of vascular endothelial growth factor, spinalradicular location, and solid type are also factors relating to the hemorrhage of hemangioblastomas. The purpose of reporting our case is 2-fold: to remind clinicians to consider the possibility of internal hemorrhaging while diagnosing this disease, and provide a starting point to discuss mechanisms regarding the intratumoral hemorrhage of hemangioblastomas. PMID:25634201

  4. Neuroinflammation after intracerebral hemorrhage

    PubMed Central

    Mracsko, Eva; Veltkamp, Roland

    2014-01-01

    Spontaneous intracerebral hemorrhage (ICH) is a particularly severe type of stroke for which no specific treatment has been established yet. Although preclinical models of ICH have substantial methodological limitations, important insight into the pathophysiology has been gained. Mounting evidence suggests an important contribution of inflammatory mechanisms to brain damage and potential repair. Neuroinflammation evoked by intracerebral blood involves the activation of resident microglia, the infiltration of systemic immune cells and the production of cytokines, chemokines, extracellular proteases and reactive oxygen species (ROS). Previous studies focused on innate immunity including microglia, monocytes and granulocytes. More recently, the role of adaptive immune cells has received increasing attention. Little is currently known about the interactions among different immune cell populations in the setting of ICH. Nevertheless, immunomodulatory strategies are already being explored in ICH. To improve the chances of translation from preclinical models to patients, a better characterization of the neuroinflammation in patients is desirable. PMID:25477782

  5. Viral Hemorrhagic Fever Diagnostics.

    PubMed

    Racsa, Lori D; Kraft, Colleen S; Olinger, Gene G; Hensley, Lisa E

    2016-01-15

    There are 4 families of viruses that cause viral hemorrhagic fever (VHF), including Filoviridae. Ebola virus is one virus within the family Filoviridae and the cause of the current outbreak of VHF in West Africa. VHF-endemic areas are found throughout the world, yet traditional diagnosis of VHF has been performed in large reference laboratories centered in Europe and the United States. The large amount of capital needed, as well as highly trained and skilled personnel, has limited the availability of diagnostics in endemic areas except in conjunction with governmental and nongovernmental entities. However, rapid diagnosis of VHF is essential to efforts that will limit outbreaks. In addition, increased global travel suggests VHF diagnoses may be made outside of the endemic areas. Thus, understanding how to diagnose VHF is imperative for laboratories worldwide. This article reviews traditional and current diagnostic modalities for VHF. PMID:26354968

  6. Molecular characterization, phylogeny analysis and pathogenicity of a Muscovy duck adenovirus strain isolated in China in 2014

    Technology Transfer Automated Retrieval System (TEKTRAN)

    This study aimed to characterize a novel adenovirus (AdV) isolated from diseased Muscovy ducks in China. After the AdV was successfully propagated in duck embryo fibroblasts, the morphological and physicochemical properties of the virions were studied by electron microscopy and different tests. The ...

  7. Evaluation of fiber-modified adenovirus vector-vaccine against foot-and-mouth diseaes in cattle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Novel vaccination approaches against foot-and-mouth-disease (FMD) include the use of a replication-defective human adenovirus type 5 vector (Ad5) that contains the capsid encoding regions of FMD virus (FMDV). An Ad5.A24 has proven effective as a vaccine against FMD in swine and cattle. However, ther...

  8. Chimpanzee Adenovirus Vector Ebola Vaccine - Preliminary Report.

    PubMed

    Ledgerwood, Julie E; DeZure, Adam D; Stanley, Daphne A; Novik, Laura; Enama, Mary E; Berkowitz, Nina M; Hu, Zonghui; Joshi, Gyan; Ploquin, Aurélie; Sitar, Sandra; Gordon, Ingelise J; Plummer, Sarah A; Holman, LaSonji A; Hendel, Cynthia S; Yamshchikov, Galina; Roman, Francois; Nicosia, Alfredo; Colloca, Stefano; Cortese, Riccardo; Bailer, Robert T; Schwartz, Richard M; Roederer, Mario; Mascola, John R; Koup, Richard A; Sullivan, Nancy J; Graham, Barney S

    2014-11-26

    Background The unprecedented 2014 epidemic of Ebola virus disease (EVD) has prompted an international response to accelerate the availability of a preventive vaccine. A replication-defective recombinant chimpanzee adenovirus type 3-vectored ebolavirus vaccine (cAd3-EBO), encoding the glycoprotein from Zaire and Sudan species that offers protection in the nonhuman primate model, was rapidly advanced into phase 1 clinical evaluation. Methods We conducted a phase 1, dose-escalation, open-label trial of cAd3-EBO. Twenty healthy adults, in sequentially enrolled groups of 10 each, received vaccination intramuscularly in doses of 2×10(10) particle units or 2×10(11) particle units. Primary and secondary end points related to safety and immunogenicity were assessed throughout the first 4 weeks after vaccination. Results In this small study, no safety concerns were identified; however, transient fever developed within 1 day after vaccination in two participants who had received the 2×10(11) particle-unit dose. Glycoprotein-specific antibodies were induced in all 20 participants; the titers were of greater magnitude in the group that received the 2×10(11) particle-unit dose than in the group that received the 2×10(10) particle-unit dose (geometric mean titer against the Zaire antigen, 2037 vs. 331; P=0.001). Glycoprotein-specific T-cell responses were more frequent among those who received the 2x10(11) particle-unit dose than among those who received the 2×10(10) particle-unit dose, with a CD4 response in 10 of 10 participants versus 3 of 10 participants (P=0.004) and a CD8 response in 7 of 10 participants versus 2 of 10 participants (P=0.07). Conclusions Reactogenicity and immune responses to cAd3-EBO vaccine were dose-dependent. At the 2×10(11) particle-unit dose, glycoprotein Zaire-specific antibody responses were in the range reported to be associated with vaccine-induced protective immunity in challenge studies involving nonhuman primates. Clinical trials

  9. Subarachnoid hemorrhage then thrombosis of posterior inferior cerebellar artery dissection: is early surgical exploration warranted?

    PubMed

    Alexiades, Nikita G; Ellis, Jason A; Meyers, Philip M; Connolly, E Sander

    2016-06-01

    The natural history of spontaneous cerebral artery dissection and thrombosis remains uncertain. Concurrent subarachnoid hemorrhage further complicates the therapeutic approach. Thus the best strategy for managing patients with acute vessel thrombosis in the setting of subarachnoid hemorrhage is unclear. Here we present a case of spontaneous posterior inferior cerebellar artery dissection presenting with subarachnoid hemorrhage and acute thrombosis. Although the patient was initially managed conservatively, angiographic follow-up demonstrated recanalization of the diseased vessel, necessitating definitive treatment. Thus we propose that angiographic follow-up is necessary in the management of patients with subarachnoid hemorrhage in association with apparent vessel thrombosis. PMID:25987592

  10. [Advance in research on the genetic etiology of spontaneous intracerebral hemorrhage].

    PubMed

    Kang, Jifeng; Huang, Qing; Liu, Yunhai

    2016-10-01

    Spontaneous intracerebral hemorrhage (SICH) is a form of brain parenchymal hemorrhage caused by a variety of non-traumatic reasons, resulting in cerebral artery, veins or capillaries rupture. The etiology of SICH is variable, with hypertensive intracerebral hemorrhage being the most common, accounting for 60% ~ 81% of all cases. Cerebral amyloid angiopathy, drug use related hemorrhage, Moyamoya disease are also important causes of SICH. Previous studies showed that genetic factors play an important role in the pathogenesis of SICH. Here the genetic mechanisms of SICH and classification of its etiology are reviewed. PMID:27577228

  11. Hypertension and vulnerability to hemorrhagic shock in a rat model.

    PubMed

    Reynolds, Penny S; Song, Kyle Seokhan; Tamariz, Francisco J; Wayne Barbee, R

    2015-02-01

    Trauma mortality may be increased in the presence of preexisting diseases such as chronic hypertension. We hypothesized that systemic and microvascular alterations accompanying chronic hypertension would increase the vulnerability to hemorrhage relative to normotensive controls in a rat model of hemorrhagic shock. We present a novel comparative hemorrhage model of shock vulnerability, quantified by "vulnerability curves" expressing physiological response to hemorrhage as a function of three matched shock metrics: cumulative blood volume, mean arterial pressure (MAP), and oxygen delivery (Do2). Responses were central hemodynamics and respiratory and muscle oxygenation obtained for one hypertensive (spontaneously hypertensive [SHR]) and two normotensive (Sprague-Dawley, Wistar-Kyoto) rat strains. Hemorrhagic shock was induced by incremental (0.5 mL) hemorrhage to cardiovascular collapse in anesthetized and mechanically ventilated animals. Shock vulnerability of SHR rats was primarily pressure-driven; in general, SHR exhibited the expected patterns of more rapid deterioration in MAP and Vo2 over smaller ranges of blood loss and Do2. Sternotomy-related depression of CO and thus Do2 in SHR meant that we could not test hypotheses related to the role of Do2 and contribution to perfusion differences between normotensive and hypertensive subjects. Insensitivity of lactate to strain effects suggests that lactate may be a reliable biomarker of shock status. Unexpected similarities between Wistar-Kyoto and SHR suggest strain-related effects other than those related to hypertension per se contribute to hemorrhage response; body size effects and genetic relationships could not be ruled out. Future studies should incorporate phylogenetically based methods to examine the role of hypertension and physiological response to hemorrhage across multiple strains. PMID:25300030

  12. [Inhibition of adenovirus reproduction in cell culture by specific antibodies].

    PubMed

    Povnytsia, O Iu; Nosach, L M; Zhovnovata, V L; Zahorodnia, S D; Vantsak, N P; Tokarchuk, L V; Polishchuk, O M; Diachenko, N S

    2009-01-01

    The capacity of specific antibodies to inhibit the reproduction of homo- and heterologous adenoviruses in Hela cell added to culture medium after virus adsorption was studied. The inhibiting effect of polyclonal antivirus and monospecific antihexone antibodies to homo- and heterologous adenoviruses was shown. The effect was more expressed when using antibodies to homologous antibodies. The intensity of inhibition depended on antibodies concentration in the medium and infecting dose of the virus. Essential reduction of the quantity of infected cells and a decrease of the titer of adenovirus synthesized in the presence of homo- and heterologous antibodies was shown but adenovirus reproduction was not inhibited completely. PMID:19663330

  13. Aerosol stability of bovine adenovirus type 3.

    PubMed Central

    Elazhary, M A; Derbyshire, J B

    1979-01-01

    The WBR-1 strain of bovine adenovirus type 3 was suspended in Eagle's medium or bovine nasal secretion and atomized into a rotating drum at temperatures of 6 degrees C or 32 degrees C and relative humidities of 30% or 90%. Impinger samples of the aerosols were collected seven minutes, one, two and three hours postgeneration, and titrated for infectivity in embryonic bovine kidney cell cultures. Under certain conditions of temperature and relative humidity, the virus was more stable in aerosols of Eagle's medium than in nasal secretion. The bovine adenovirus was usually inactivated more rapidly at 30% relative humidity than at 90% relative humidity and during aging of the aerosols the virus was inactivated more rapidly at 32 degrees C than at 6 degrees C. PMID:226247

  14. Structure, Function and Dynamics in Adenovirus Maturation

    PubMed Central

    Mangel, Walter F.; San Martín, Carmen

    2014-01-01

    Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and core precursor proteins by the viral protease (AVP). AVP uses a peptide cleaved from one of its targets as a “molecular sled” to slide on the viral genome and reach its substrates, in a remarkable example of one-dimensional chemistry. Immature adenovirus containing the precursor proteins lacks infectivity because of its inability to uncoat. The immature core is more compact and stable than the mature one, due to the condensing action of unprocessed core polypeptides; shell precursors underpin the vertex region and the connections between capsid and core. Maturation makes the virion metastable, priming it for stepwise uncoating by facilitating vertex release and loosening the condensed genome and its attachment to the icosahedral shell. The packaging scaffold protein L1 52/55k is also a substrate for AVP. Proteolytic processing of L1 52/55k disrupts its interactions with other virion components, providing a mechanism for its removal during maturation. Finally, possible roles for maturation of the terminal protein are discussed. PMID:25421887

  15. Structure, function and dynamics in adenovirus maturation

    SciTech Connect

    Mangel, Walter F.; San Martín, Carmen

    2014-11-21

    Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and core precursor proteins by the viral protease (AVP). AVP uses a peptide cleaved from one of its targets as a “molecular sled” to slide on the viral genome and reach its substrates, in a remarkable example of one-dimensional chemistry. Immature adenovirus containing the precursor proteins lacks infectivity because of its inability to uncoat. The immature core is more compact and stable than the mature one, due to the condensing action of unprocessed core polypeptides; shell precursors underpin the vertex region and the connections between capsid and core. Maturation makes the virion metastable, priming it for stepwise uncoating by facilitating vertex release and loosening the condensed genome and its attachment to the icosahedral shell. The packaging scaffold protein L1 52/55k is also a substrate for AVP. Proteolytic processing of L1 52/55k disrupts its interactions with other virion components, providing a mechanism for its removal during maturation. In conclusion, possible roles for maturation of the terminal protein are discussed.

  16. Structure, function and dynamics in adenovirus maturation

    DOE PAGESBeta

    Mangel, Walter F.; San Martín, Carmen

    2014-11-21

    Here we review the current knowledge on maturation of adenovirus, a non-enveloped icosahedral eukaryotic virus. The adenovirus dsDNA genome fills the capsid in complex with a large amount of histone-like viral proteins, forming the core. Maturation involves proteolytic cleavage of several capsid and core precursor proteins by the viral protease (AVP). AVP uses a peptide cleaved from one of its targets as a “molecular sled” to slide on the viral genome and reach its substrates, in a remarkable example of one-dimensional chemistry. Immature adenovirus containing the precursor proteins lacks infectivity because of its inability to uncoat. The immature core ismore » more compact and stable than the mature one, due to the condensing action of unprocessed core polypeptides; shell precursors underpin the vertex region and the connections between capsid and core. Maturation makes the virion metastable, priming it for stepwise uncoating by facilitating vertex release and loosening the condensed genome and its attachment to the icosahedral shell. The packaging scaffold protein L1 52/55k is also a substrate for AVP. Proteolytic processing of L1 52/55k disrupts its interactions with other virion components, providing a mechanism for its removal during maturation. In conclusion, possible roles for maturation of the terminal protein are discussed.« less

  17. ADENOVIRUS INTERACTION WITH ITS CELLULAR RECEPTOR CAR.

    SciTech Connect

    HOWITT,J.; ANDERSON,C.W.; FREIMUTH,P.

    2001-08-01

    The mechanism of adenovirus attachment to the host cell plasma membrane has been revealed in detail by research over the past 10 years. It has long been known that receptor binding activity is associated with the viral fibers, trimeric spike proteins that protrude radially from the vertices of the icosahedral capsid (Philipson et al. 1968). In some adenovirus serotypes, fiber and other virus structural proteins are synthesized in excess and accumulate in the cell nucleus during late stages of infection. Fiber protein can be readily purified from lysates of cells infected with subgroup C viruses, for example Ad2 and Ad5 (Boulanger and Puvion 1973). Addition of purified fiber protein to virus suspensions during adsorption strongly inhibits infection, indicating that fiber and intact virus particles compete for binding sites on host cells (Philipson et al. 1968; Hautala et al. 1998). Cell binding studies using purified radiolabeled fiber demonstrated that fiber binds specifically and with high affinity to the cell plasma membrane, and that cell lines typically used for laboratory propagation of adenovirus have approximately 10{sup 4} high-affinity receptor sites per cell (Persson et al. 1985; Freimuth 1996). Similar numbers of high-affinity binding sites for radiolabeled intact virus particles also were observed (Seth et al. 1994).

  18. Cerebral Cavernous Malformation and Hemorrhage

    MedlinePlus

    ... absorption, unmasking the lesion's boundary relative to healthy brain tissue; however, if surgery is contemplated, it should not be delayed so long after a bleed that the lesion begins to shrink, making extraction more difficult. Hemorrhage Rates What is ...

  19. Methods for improved hemorrhage control

    PubMed Central

    2004-01-01

    Trauma is the leading cause of death from age 1 to 34 years and is the fifth leading cause of death overall in the USA, with uncontrolled hemorrhage being the leading cause of potentially preventable death. Improving our ability to control hemorrhage may represent the next major hurdle in reducing trauma mortality. New techniques, devices, and drugs for hemorrhage control are being developed and applied across the continuum of trauma care: prehospital, emergency room, and operative and postoperative critical care. This brief review focuses on drugs directed at life-threatening hemorrhage. The most important of these new drugs are injectable hemostatics, fibrin foams, and dressings. The available animal studies are encouraging and human studies are required. PMID:15196327

  20. Hemorrhagic complications in dermatologic surgery

    PubMed Central

    Bunick, Christopher G.; Aasi, Sumaira Z.

    2014-01-01

    The ability to recognize, manage, and, most importantly, prevent hemorrhagic complications is critical to performing dermatologic procedures that have safe and high quality outcomes. This article reviews the preoperative, intraoperative, and postoperative factors and patient dynamics that are central to preventing such an adverse outcome. Specifically, the role that anticoagulants and antiplatelet agents, hypertension, and other medical conditions play in the development of postoperative hemorrhage are discussed. In addition, this article provides practical guidelines on managing bleeding during and after surgery. PMID:22515669

  1. Fatal pulmonary hemorrhage after taking anticoagulation medication

    PubMed Central

    Hammar, Samuel P.

    2015-01-01

    We describe a 64-year-old man with extensive diffuse acute lung hemorrhage, presumably as a result of anticoagulation therapy. We evaluated reports in the literature concerning acute exacerbation (acute lung injury of unknown cause) in UIP and other forms of fibrotic interstitial pneumonias. We also evaluated autopsy tissue in this case in order to determine the cause of death in this 64-year-old man, who was initially thought to have an asbestos-related disease. Based on the autopsy findings, this man died as a result of anticoagulation therapy; specifically, the use of Xarelto® (rivaroxaban). PMID:26236607

  2. Endothelial cells in dengue hemorrhagic fever.

    PubMed

    Srikiatkhachorn, Anon; Kelley, James F

    2014-09-01

    Therapies to prevent or reverse endothelial dysfunction and vascular leak found in dengue hemorrhagic fever (DHF) have not been identified. In this review we summarize dengue viruses and the spectrum of human disease and highlight evidence of endothelial cell dysfunction in DHF based on studies in patients and mouse and tissue culture models. Evidence suggests that both virus antigen and host immune response, can cause endothelial cell dysfunction and weaken endothelial barrier integrity. We suggest possible therapeutic interventions and highlight how therapies targeting altered endothelial function might be evaluated in animal models and in patients with DHF. PMID:25025934

  3. [Enteroviruses responsible for acute hemorrhagic conjunctivitis].

    PubMed

    Lévêque, N; Huguet, P; Norder, H; Chomel, J-J

    2010-04-01

    Acute hemorrhagic conjunctivitis (AHC) is an epidemic form of highly contagious conjunctivitis, characterized by conjunctival hemorrhages. The first AHC outbreak was described in 1969 in Ghana, West Africa, and was called Apollo disease, from the Apollo landing on the moon. This outbreak was caused by Enterovirus 70 (EV70) together with a Coxsackievirus A24 (CVA24v) variant, which are the major etiological agents involved in AHC outbreaks worldwide. AHC is known to be directly transmitted by close person-to-person contact or indirectly through soiled ophthalmological materials or unsafe recreational water. Recently, a possible airborne virus spread was suggested which could explain the high transmission rate of the disease. In the absence of a specific antiviral therapy, a rapid diagnosis of the causative agent is required to distinguish AHC due to enteroviruses from other ocular infectious diseases, for there are active drugs, or to quickly implement proper public health measures to limit the extension of the outbreak. However, virus identification remains difficult and time-consuming. Moreover, virological diagnosis is difficult to implement in developing countries where AHC has recently become a major problem for public health. PMID:19836177

  4. A retrospective investigation of canine adenovirus (CAV) infection in adult dogs in Turkey.

    PubMed

    Gür, S; Acar, A

    2009-06-01

    Canine adenovirus (CAV) type 1 and 2, respectively, cause infectious canine hepatitis and infectious canine laryngotracheitis in members of the families Canidae and Ursidae worldwide. Both of these infections are acute diseases, especially in young dogs. The aim of this study was to conduct a serological investigation of canine adenovirus infection. For this purpose, serum samples were collected from native pure-bred Kangal(n = 11), and Akbash dogs (n = 17) and Turkish Greyhounds (n = 15) in Eskişehir and Konya provinces. None of the dogs were previously vaccinated against CAV types. Indirect ELISA detected 88.2%, 93.3% and 100% prevalences in Akbash, Greyhound and Kangal dogs, respectively. The remainder of the samples (n = 51) were collected at the Afyonkarahisar Municipality Shelter. Fourty-two of these dogs (82.3%) were detected as seropositive. In total, 82 of 94 dogs (87.2%) were found to be positive for CAV serum antibodies. PMID:19831268

  5. Methods and clinical development of adenovirus-vectored vaccines against mucosal pathogens

    PubMed Central

    Afkhami, Sam; Yao, Yushi; Xing, Zhou

    2016-01-01

    Adenoviruses represent the most widely used viral-vectored platform for vaccine design, showing a great potential in the fight against intracellular infectious diseases to which either there is a lack of effective vaccines or the traditional vaccination strategy is suboptimal. The extensive understanding of the molecular biology of adenoviruses has made the new technologies and reagents available to efficient generation of adenoviral-vectored vaccines for both preclinical and clinical evaluation. The novel adenoviral vectors including nonhuman adenoviral vectors have emerged to be the further improved vectors for vaccine design. In this review, we discuss the latest adenoviral technologies and their utilization in vaccine development. We particularly focus on the application of adenoviral-vectored vaccines in mucosal immunization strategies against mucosal pathogens including Mycobacterium tuberculosis, flu virus, and human immunodeficiency virus. PMID:27162933

  6. Chimpanzee adenovirus vaccine generates acute and durable protective immunity against ebolavirus challenge.

    PubMed

    Stanley, Daphne A; Honko, Anna N; Asiedu, Clement; Trefry, John C; Lau-Kilby, Annie W; Johnson, Joshua C; Hensley, Lisa; Ammendola, Virginia; Abbate, Adele; Grazioli, Fabiana; Foulds, Kathryn E; Cheng, Cheng; Wang, Lingshu; Donaldson, Mitzi M; Colloca, Stefano; Folgori, Antonella; Roederer, Mario; Nabel, Gary J; Mascola, John; Nicosia, Alfredo; Cortese, Riccardo; Koup, Richard A; Sullivan, Nancy J

    2014-10-01

    Ebolavirus disease causes high mortality, and the current outbreak has spread unabated through West Africa. Human adenovirus type 5 vectors (rAd5) encoding ebolavirus glycoprotein (GP) generate protective immunity against acute lethal Zaire ebolavirus (EBOV) challenge in macaques, but fail to protect animals immune to Ad5, suggesting natural Ad5 exposure may limit vaccine efficacy in humans. Here we show that a chimpanzee-derived replication-defective adenovirus (ChAd) vaccine also rapidly induced uniform protection against acute lethal EBOV challenge in macaques. Because protection waned over several months, we boosted ChAd3 with modified vaccinia Ankara (MVA) and generated, for the first time, durable protection against lethal EBOV challenge. PMID:25194571

  7. Spread of Adenovirus to Geographically Dispersed Military Installations, May–October 2007

    PubMed Central

    Trei, Jill S.; Garner, Jason L.; Noel, Lawrence B.; Ortman, Brian V.; Ensz, Kari L.; Johns, Matthew C.; Bunning, Michel L.; Gaydos, Joel C.

    2010-01-01

    In mid-May 2007, a respiratory disease outbreak associated with adenovirus, serotype B14 (Ad14), was recognized at a large military basic training facility in Texas. The affected population was highly mobile; after the 6-week basic training course, trainees immediately dispersed to advanced training sites worldwide. Accordingly, enhanced surveillance and control efforts were instituted at sites receiving the most trainees. Specimens from patients with pneumonia or febrile respiratory illness were tested for respiratory pathogens by using cultures and reverse transcription–PCR. During May through October 2007, a total of 959 specimens were collected from 21 sites; 43.1% were adenovirus positive; the Ad14 serotype accounted for 95.3% of adenovirus isolates. Ad14 was identified at 8 sites in California, Florida, Mississippi, Texas, and South Korea. Ad14 spread readily to secondary sites after the initial outbreak. Military and civilian planners must consider how best to control the spread of infectious respiratory diseases in highly mobile populations traveling between diverse geographic locations. PMID:20409365

  8. The Serological and Virological Investigation of Canine Adenovirus Infection on the Dogs

    PubMed Central

    Bulut, Oya; Yapici, Orhan; Avci, Oguzhan; Simsek, Atilla; Atli, Kamil; Dik, Irmak; Yavru, Sibel; Hasircioglu, Sibel; Kale, Mehmet; Mamak, Nuri

    2013-01-01

    Two types of Canine Adenovirus (CAVs), Canine Adenovirus type 1 (CAV-1), the virus which causes infectious canine hepatitis, and Canine Adenovirus type 2 (CAV-2), which causes canine infectious laryngotracheitis, have been found in dogs. In this study, blood samples taken from 111 dogs, which were admitted to the Internal Medicine Clinic of Selcuk University, Faculty of Veterinary Medicine, with clinical symptoms. Seventy-seven dogs were sampled from Isparta and Burdur dog shelters by random sampling, regardless of the clinical findings. Dogs showed a systemic disease, characterized by fever, diarrhea, vomiting, oculonasal discharge, conjunctivitis, severe moist cough, signs of pulmonary disease and dehydration. Two dogs had corneal opacity and photophobia. In serological studies, 188 serum samples were investigated on the presence of CAV antibodies by ELISA. Total 103 (103/188–54.7%) blood samples were detected to be positive for CAV antibodies by ELISA. However, 85 (85/188–45.2%) blood samples were negative. Blood leukocyte samples from dogs were processed and inoculated onto confluent monolayers of MDCK cells using standard virological techniques. After third passage, cells were examined by direct immunoflourescence test for virus isolation. But positive result was not detected. In conclusion, this study clearly demonstrates the high prevalence of CAV infection in dogs. PMID:24223508

  9. The serological and virological investigation of canine adenovirus infection on the dogs.

    PubMed

    Bulut, Oya; Yapici, Orhan; Avci, Oguzhan; Simsek, Atilla; Atli, Kamil; Dik, Irmak; Yavru, Sibel; Hasircioglu, Sibel; Kale, Mehmet; Mamak, Nuri

    2013-01-01

    Two types of Canine Adenovirus (CAVs), Canine Adenovirus type 1 (CAV-1), the virus which causes infectious canine hepatitis, and Canine Adenovirus type 2 (CAV-2), which causes canine infectious laryngotracheitis, have been found in dogs. In this study, blood samples taken from 111 dogs, which were admitted to the Internal Medicine Clinic of Selcuk University, Faculty of Veterinary Medicine, with clinical symptoms. Seventy-seven dogs were sampled from Isparta and Burdur dog shelters by random sampling, regardless of the clinical findings. Dogs showed a systemic disease, characterized by fever, diarrhea, vomiting, oculonasal discharge, conjunctivitis, severe moist cough, signs of pulmonary disease and dehydration. Two dogs had corneal opacity and photophobia. In serological studies, 188 serum samples were investigated on the presence of CAV antibodies by ELISA. Total 103 (103/188-54.7%) blood samples were detected to be positive for CAV antibodies by ELISA. However, 85 (85/188-45.2%) blood samples were negative. Blood leukocyte samples from dogs were processed and inoculated onto confluent monolayers of MDCK cells using standard virological techniques. After third passage, cells were examined by direct immunoflourescence test for virus isolation. But positive result was not detected. In conclusion, this study clearly demonstrates the high prevalence of CAV infection in dogs. PMID:24223508

  10. Adenovirus vectors targeting distinct cell types in the retina.

    PubMed

    Sweigard, J Harry; Cashman, Siobhan M; Kumar-Singh, Rajendra

    2010-04-01

    Purpose. Gene therapy for a number of retinal diseases necessitates efficient transduction of photoreceptor cells. Whereas adenovirus (Ad) serotype 5 (Ad5) does not transduce photoreceptors efficiently, previous studies have demonstrated improved photoreceptor transduction by Ad5 pseudotyped with Ad35 (Ad5/F35) or Ad37 (Ad5/F37) fiber or by the deletion of the RGD domain in the Ad5 penton base (Ad5DeltaRGD). However, each of these constructs contained a different transgene cassette, preventing the evaluation of the relative performance of these vectors, an important consideration before the use of these vectors in the clinic. The aim of this study was to evaluate these vectors in the retina and to attempt photoreceptor-specific transgene expression. Methods. Three Ad5-based vectors containing the same expression cassette were generated and injected into the subretinal space of adult mice. Eyes were analyzed for green fluorescence protein expression in flat-mounts, cross-sections, quantitative RT-PCR, and a modified stereological technique. A 257-bp fragment derived from the mouse opsin promoter was analyzed in the context of photoreceptor-specific transgene expression. Results. Each virus tested efficiently transduced the retinal pigment epithelium. The authors found no evidence that Ad5/F35 or Ad5/F37 transduced photoreceptors. Instead, they found that Ad5/F37 transduced Müller cells. Robust photoreceptor transduction by Ad5DeltaRGD was detected. Photoreceptor-specific transgene expression from the 257-bp mouse opsin promoter in the context of Ad5DeltaRGD vectors was found. Conclusions. Adenovirus vectors may be designed with tropism to distinct cell populations. Robust photoreceptor-specific transgene expression can be achieved in the context of Ad5DeltaRGD vectors. PMID:19892875

  11. Enhanced inactivation of adenovirus under polychromatic UV lamps

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Adenovirus is recognized as the most UV-resistant waterborne pathogen of concern to public health microbiologists. The US EPA has stipulated that a UV fluence (dose) of 186 mJ cm-2 is required for 4-log inactivation credit in water treatment. However, all adenovirus inactivation data to date publi...

  12. Capturing and concentrating adenovirus using magnetic anionic nanobeads.

    PubMed

    Sakudo, Akikazu; Baba, Koichi; Ikuta, Kazuyoshi

    2016-01-01

    We recently demonstrated how various enveloped viruses can be efficiently concentrated using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate). However, the exact mechanism of interaction between the virus particles and anionic beads remains unclear. To further investigate whether these magnetic anionic beads specifically bind to the viral envelope, we examined their potential interaction with a nonenveloped virus (adenovirus). The beads were incubated with either adenovirus-infected cell culture medium or nasal aspirates from adenovirus-infected individuals and then separated from the supernatant by applying a magnetic field. After thoroughly washing the beads, adsorption of adenovirus was confirmed by a variety of techniques, including immunochromatography, polymerase chain reaction, Western blotting, and cell culture infection assays. These detection methods positively identified the hexon and penton capsid proteins of adenovirus along with the viral genome on the magnetic beads. Furthermore, various types of adenovirus including Types 5, 6, 11, 19, and 41 were captured using the magnetic bead procedure. Our bead capture method was also found to increase the sensitivity of viral detection. Adenovirus below the detectable limit for immunochromatography was efficiently concentrated using the magnetic bead procedure, allowing the virus to be successfully detected using this methodology. Moreover, these findings clearly demonstrate that a viral envelope is not required for binding to the anionic magnetic beads. Taken together, our results show that this capture procedure increases the sensitivity of detection of adenovirus and would, therefore, be a valuable tool for analyzing both clinical and experimental samples. PMID:27274228

  13. Capturing and concentrating adenovirus using magnetic anionic nanobeads

    PubMed Central

    Sakudo, Akikazu; Baba, Koichi; Ikuta, Kazuyoshi

    2016-01-01

    We recently demonstrated how various enveloped viruses can be efficiently concentrated using magnetic beads coated with an anionic polymer, poly(methyl vinyl ether-maleic anhydrate). However, the exact mechanism of interaction between the virus particles and anionic beads remains unclear. To further investigate whether these magnetic anionic beads specifically bind to the viral envelope, we examined their potential interaction with a nonenveloped virus (adenovirus). The beads were incubated with either adenovirus-infected cell culture medium or nasal aspirates from adenovirus-infected individuals and then separated from the supernatant by applying a magnetic field. After thoroughly washing the beads, adsorption of adenovirus was confirmed by a variety of techniques, including immunochromatography, polymerase chain reaction, Western blotting, and cell culture infection assays. These detection methods positively identified the hexon and penton capsid proteins of adenovirus along with the viral genome on the magnetic beads. Furthermore, various types of adenovirus including Types 5, 6, 11, 19, and 41 were captured using the magnetic bead procedure. Our bead capture method was also found to increase the sensitivity of viral detection. Adenovirus below the detectable limit for immunochromatography was efficiently concentrated using the magnetic bead procedure, allowing the virus to be successfully detected using this methodology. Moreover, these findings clearly demonstrate that a viral envelope is not required for binding to the anionic magnetic beads. Taken together, our results show that this capture procedure increases the sensitivity of detection of adenovirus and would, therefore, be a valuable tool for analyzing both clinical and experimental samples. PMID:27274228

  14. Successful treatment with intravesical cidofovir for virus-associated hemorrhagic cystitis after allogeneic hematopoietic stem cell transplantation: A case report and a review of the literature.

    PubMed

    Sakurada, Maki; Kondo, Tadakazu; Umeda, Masayuki; Kawabata, Hiroshi; Yamashita, Kouhei; Takaori-Kondo, Akifum

    2016-07-01

    Virus-associated hemorrhagic cystitis (VAHC) is a formidable complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The standard management of severe VAHC after allo-HSCT has not been established. Intravenous administration of cidofovir (CDV), an acyclic nucleoside analogue with broad-spectrum activity against DNA viruses, has been reported to be effective for VAHC, but it can cause severe renal toxicity. Here we report four cases who achieved clinical responses with intravesical instillation of CDV for severe VAHC after allo-HSCT. Median age was 57 years (40-63), and all were male. The underlying diseases were hematological malignancies. Three had received bone marrow transplantation, and one received cord blood transplantation twice. Conditioning regimen was myeloablative for one, and reduced-intensity for three. The viral types were BK virus and/or adenovirus. Two patients had received CDV intravenously prior to the intravesical therapy. A dose of intravesical CDV was 2-5 mg/kg. In all cases, symptoms of cystitis improved dramatically within a few days without showing any systemic adverse effects. The virological response was observed in two cases. This local therapy was effective even in the cases refractory to the intravenous CDV and a case with severe renal failure. Along with the review of literature, we propose that the intravesical instillation of CDV can be a therapeutic option for severe VAHC after allo-HSCT. PMID:26898668

  15. Immunological features underlying viral hemorrhagic fevers.

    PubMed

    Messaoudi, Ilhem; Basler, Christopher F

    2015-10-01

    Several enveloped RNA viruses of the arenavirus, bunyavirus, filovirus and flavivirus families are associated with a syndrome known as viral hemorrhagic fever (VHF). VHF is characterized by fever, vascular leakage, coagulation defects and multi organ system failure. VHF is currently viewed as a disease precipitated by viral suppression of innate immunity, which promotes systemic virus replication and excessive proinflammatory cytokine responses that trigger the manifestations of severe disease. However, the mechanisms by which immune dysregulation contributes to disease remain poorly understood. Infection of nonhuman primates closely recapitulates human VHF, notably Ebola and yellow fever, thereby providing excellent models to better define the immunological basis for this syndrome. Here we review the current state of our knowledge and suggest future directions that will better define the immunological mechanisms underlying VHF. PMID:26163194

  16. Adenovirus and herpesvirus diversity in free-ranging great apes in the Sangha region of the Republic Of Congo.

    PubMed

    Seimon, Tracie A; Olson, Sarah H; Lee, Kerry Jo; Rosen, Gail; Ondzie, Alain; Cameron, Kenneth; Reed, Patricia; Anthony, Simon J; Joly, Damien O; Karesh, William B; McAloose, Denise; Lipkin, W Ian

    2015-01-01

    Infectious diseases have caused die-offs in both free-ranging gorillas and chimpanzees. Understanding pathogen diversity and disease ecology is therefore critical for conserving these endangered animals. To determine viral diversity in free-ranging, non-habituated gorillas and chimpanzees in the Republic of Congo, genetic testing was performed on great-ape fecal samples collected near Odzala-Kokoua National Park. Samples were analyzed to determine ape species, identify individuals in the population, and to test for the presence of herpesviruses, adenoviruses, poxviruses, bocaviruses, flaviviruses, paramyxoviruses, coronaviruses, filoviruses, and simian immunodeficiency virus (SIV). We identified 19 DNA viruses representing two viral families, Herpesviridae and Adenoviridae, of which three herpesviruses had not been previously described. Co-detections of multiple herpesviruses and/or adenoviruses were present in both gorillas and chimpanzees. Cytomegalovirus (CMV) and lymphocryptovirus (LCV) were found primarily in the context of co-association with each other and adenoviruses. Using viral discovery curves for herpesviruses and adenoviruses, the total viral richness in the sample population of gorillas and chimpanzees was estimated to be a minimum of 23 viruses, corresponding to a detection rate of 83%. These findings represent the first description of DNA viral diversity in feces from free-ranging gorillas and chimpanzees in or near the Odzala-Kokoua National Park and form a basis for understanding the types of viruses circulating among great apes in this region. PMID:25781992

  17. Biodistribution Analysis of Oncolytic Adenoviruses in Patient Autopsy Samples Reveals Vascular Transduction of Noninjected Tumors and Tissues.

    PubMed

    Koski, Anniina; Bramante, Simona; Kipar, Anja; Oksanen, Minna; Juhila, Juuso; Vassilev, Lotta; Joensuu, Timo; Kanerva, Anna; Hemminki, Akseli

    2015-10-01

    In clinical trials with oncolytic adenoviruses, there has been no mortality associated with treatment vectors. Likewise, in the Advanced Therapy Access Program (ATAP), where 290 patients were treated with 10 different viruses, no vector-related mortality was observed. However, as the patient population who received adenovirus treatments in ATAP represented heavily pretreated patients, often with very advanced disease, some patients died relatively soon after receiving their virus treatment mandating autopsy to investigate cause of death. Eleven such autopsies were performed and confirmed disease progression as the cause of death in each case. The regulatory requirement for investigating the safety of advanced therapy medical products presented a unique opportunity to study tissue samples collected as a routine part of the autopsies. Oncolytic adenoviral DNA was recovered in a wide range of tissues, including injected and noninjected tumors and various normal tissues, demonstrating the ability of the vector to disseminate through the vascular route. Furthermore, we recovered and cultured viable virus from samples of noninjected brain metastases of an intravenously treated patient, confirming that oncolytic adenovirus can reach tumors through the intravascular route. Data presented here give mechanistic insight into mode of action and biodistribution of oncolytic adenoviruses in cancer patients. PMID:26156245

  18. Adenovirus and Herpesvirus Diversity in Free-Ranging Great Apes in the Sangha Region of the Republic of Congo

    PubMed Central

    Seimon, Tracie A.; Olson, Sarah H.; Lee, Kerry Jo; Rosen, Gail; Ondzie, Alain; Cameron, Kenneth; Reed, Patricia; Anthony, Simon J.; Joly, Damien O.; McAloose, Denise; Lipkin, W. Ian

    2015-01-01

    Infectious diseases have caused die-offs in both free-ranging gorillas and chimpanzees. Understanding pathogen diversity and disease ecology is therefore critical for conserving these endangered animals. To determine viral diversity in free-ranging, non-habituated gorillas and chimpanzees in the Republic of Congo, genetic testing was performed on great-ape fecal samples collected near Odzala-Kokoua National Park. Samples were analyzed to determine ape species, identify individuals in the population, and to test for the presence of herpesviruses, adenoviruses, poxviruses, bocaviruses, flaviviruses, paramyxoviruses, coronaviruses, filoviruses, and simian immunodeficiency virus (SIV). We identified 19 DNA viruses representing two viral families, Herpesviridae and Adenoviridae, of which three herpesviruses had not been previously described. Co-detections of multiple herpesviruses and/or adenoviruses were present in both gorillas and chimpanzees. Cytomegalovirus (CMV) and lymphocryptovirus (LCV) were found primarily in the context of co-association with each other and adenoviruses. Using viral discovery curves for herpesviruses and adenoviruses, the total viral richness in the sample population of gorillas and chimpanzees was estimated to be a minimum of 23 viruses, corresponding to a detection rate of 83%. These findings represent the first description of DNA viral diversity in feces from free-ranging gorillas and chimpanzees in or near the Odzala-Kokoua National Park and form a basis for understanding the types of viruses circulating among great apes in this region. PMID:25781992

  19. Aneurysmal Subarachnoid Hemorrhage.

    PubMed

    D'Souza, Stanlies

    2015-07-01

    Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome. PMID:25272066

  20. Aneurysmal Subarachnoid Hemorrhage

    PubMed Central

    2015-01-01

    Aneurysmal subarachnoid hemorrhage (SAH) is a worldwide health burden with high fatality and permanent disability rates. The overall prognosis depends on the volume of the initial bleed, rebleeding, and degree of delayed cerebral ischemia (DCI). Cardiac manifestations and neurogenic pulmonary edema indicate the severity of SAH. The International Subarachnoid Aneurysm Trial (ISAT) reported a favorable neurological outcome with the endovascular coiling procedure compared with surgical clipping at the end of 1 year. The ISAT trial recruits were primarily neurologically good grade patients with smaller anterior circulation aneurysms, and therefore the results cannot be reliably extrapolated to larger aneurysms, posterior circulation aneurysms, patients presenting with complex aneurysm morphology, and poor neurological grades. The role of hypothermia is not proven to be neuroprotective according to a large randomized controlled trial, Intraoperative Hypothermia for Aneurysms Surgery Trial (IHAST II), which recruited patients with good neurological grades. Patients in this trial were subjected to slow cooling and inadequate cooling time and were rewarmed rapidly. This methodology would have reduced the beneficial effects of hypothermia. Adenosine is found to be beneficial for transient induced hypotension in 2 retrospective analyses, without increasing the risk for cardiac and neurological morbidity. The neurological benefit of pharmacological neuroprotection and neuromonitoring is not proven in patients undergoing clipping of aneurysms. DCI is an important cause of morbidity and mortality following SAH, and the pathophysiology is likely multifactorial and not yet understood. At present, oral nimodipine has an established role in the management of DCI, along with maintenance of euvolemia and induced hypertension. Following SAH, hypernatremia, although less common than hyponatremia, is a predictor of poor neurological outcome. PMID:25272066

  1. Obstetric hemorrhage: A global review.

    PubMed

    Goffman, Dena; Nathan, Lisa; Chazotte, Cynthia

    2016-03-01

    Postpartum hemorrhage remains the number one cause of maternal death globally despite the fact that it is largely a preventable and most often a treatable condition. While the global problem is appreciated, some may not realize that in the United States postpartum hemorrhage is a leading cause of mortality and unfortunately, the incidence is on the rise. In New York, obstetric hemorrhage is the second leading cause of maternal mortality in the state. National data suggests that hemorrhage is disproportionally overrepresented as a contributor to severe maternal morbidity and we suspect as we explore further this will be true in New York State as well. Given the persistent and significant contribution to maternal mortality, it may be useful to analyze the persistence of this largely preventable cause of death within the framework of the historic "Three Delays" model of maternal mortality. The ongoing national and statewide problem with postpartum hemorrhage will be reviewed in this context of delays in an effort to inform potential solutions. PMID:26742599

  2. PEGylated Adenoviruses: From Mice to Monkeys

    PubMed Central

    Wonganan, Piyanuch; Croyle, Maria A.

    2010-01-01

    Covalent modification with polyethylene glycol (PEG), a non-toxic polymer used in food, cosmetic and pharmaceutical preparations for over 60 years, can profoundly influence the pharmacokinetic, pharmacologic and toxciologic profile of protein and peptide-based therapeutics. This review summarizes the history of PEGylation and PEG chemistry and highlights the value of this technology in the context of the design and development of recombinant viruses for gene transfer, vaccination and diagnostic purposes. Specific emphasis is placed on the application of this technology to the adenovirus, the most potent viral vector with the most highly characterized toxicity profile to date, in several animal models. PMID:21994645

  3. Evaluation of Temporal Association Between Vaccinations and Retinal Hemorrhage in Children

    PubMed Central

    Binenbaum, Gil; Christian, Cindy W.; Guttmann, Katy; Huang, Jiayan; Ying, Gui-shuang; Forbes, Brian J.

    2016-01-01

    ). Conclusions and Relevance Retinal hemorrhage was rare among outpatients younger than 2 years. Considering both immediate and delayed effects, no temporal association existed between vaccination injection and retinal hemorrhage. Vaccination injections should not be considered a potential cause of retinal hemorrhage in children, and this unsupported theory should not be accepted clinically or in legal proceedings. Ophthalmologists noting incidental retinal hemorrhage on an outpatient examination should consider a child abuse evaluation in the absence of other known ocular or medical disease. PMID:26335082

  4. Phylogenetic and geographic analysis of fowl adenovirus field strains isolated from poultry in Poland.

    PubMed

    Niczyporuk, Jowita Samanta

    2016-01-01

    Fowl adenoviruses (FAdVs) are widely distributed in chickens in Poland and throughout the world. FAdV infections have been reported in the United States, Australia, Europe, and the Mediterranean basin. Detection of FAdVs strains is very important from the epidemiological point of view and for monitoring disease outbreaks and developing strategies for vaccine development. Several molecular epidemiology and phylogenetic studies have been performed, but the results obtained are still limited, because FAdV strains, even of the same serotype, have very diverse characteristics. Some strains are pathogenic and some are nonpathogenic. This report describes the successful isolation of 96 FAdV field strains from chickens in Poland. A PCR assay specific for the L1 loop region of the hexon gene was conducted, and the products were subjected to sequence analysis. The sequences were analysed using BLAST and Geneious 6.0 software and compared to adenovirus field and reference strain sequences from different parts of the world that are accessible in the NCBI GenBank database. The sequences of the adenovirus strains indicated that they belonged to five species, Fowl aviadenovirus A-E, represented by eight serotypes FAdV-1, FAdV-4, FAdV-5, FAdV-7, FAdV-8a, FAdV-8b, and FAdV-2/11 (FAdV-D). The relationships between FAdVs isolated in Poland and isolates from other regions of the world were determined. PMID:26446890

  5. Enhanced Transduction and Replication of RGD-Fiber Modified Adenovirus in Primary T Cells

    PubMed Central

    Sengupta, Sadhak; Ulasov, Ilya V.; Thaci, Bart; Ahmed, Atique U.; Lesniak, Maciej S.

    2011-01-01

    Background Adenoviruses are often used as vehicles to mediate gene delivery for therapeutic purposes, but their research scope in hematological cells remains limited due to a narrow choice of host cells that express the adenoviral receptor (CAR). T cells, which are attractive targets for gene therapy of numerous diseases, remain resistant to adenoviral infection because of the absence of CAR expression. Here, we demonstrate that this resistance can be overcome when murine or human T cells are transduced with an adenovirus incorporating the RGD-fiber modification (Ad-RGD). Methodology/Principal Finding A luciferase-expressing replication-deficient Ad-RGD infected 3-fold higher number of activated primary T cells than an adenovirus lacking the RGD-fiber modification in vitro. Infection with replication-competent Ad-RGD virus also caused increased cell cycling, higher E1A copy number and enriched hexon antigen expression in both human and murine T cells. Transduction with oncolytic Ad-RGD also resulted in higher titers of progeny virus and enhanced the killing of T cells. In vivo, 35–45% of splenic T cells were transduced by Ad-RGD. Conclusions Collectively, our results prove that a fiber modified Ad-RGD successfully transduces and replicates in primary T cells of both murine and human origin. PMID:21464908

  6. Efficient adenovirus-mediated transfer of a human minidystrophin gene to skeletal muscle of mdx mice.

    PubMed

    Ragot, T; Vincent, N; Chafey, P; Vigne, E; Gilgenkrantz, H; Couton, D; Cartaud, J; Briand, P; Kaplan, J C; Perricaudet, M

    1993-02-18

    Duchenne progressive muscular dystrophy is a lethal and common X-linked genetic disease caused by the absence of dystrophin, a 427K protein encoded by a 14 kilobase transcript. Two approaches have been proposed to correct the dystrophin deficiency in muscle. The first, myoblast transfer therapy, uses cells from normal donors, whereas the second involves direct intramuscular injection of recombinant plasmids expressing dystrophin. Adenovirus is an efficient vector for in vivo expression of various foreign genes. It has recently been demonstrated that a recombinant adenovirus expressing the lac-Z reporter gene can infect stably many mouse tissues, particularly muscle and heart. We have tested the ability of a recombinant adenovirus, containing a 6.3 kilobase pair Becker-like dystrophin complementary DNA driven by the Rous sarcoma virus promoter to direct the expression of a 'minidystrophin' in infected 293 cells and C2 myoblasts, and in the mdx mouse, after intramuscular injection. We report here that in vivo, we have obtained a sarcolemmal immunostaining in up to 50% of fibres of the injected muscle. PMID:8437625

  7. In vivo expression of adenovirus-mediated lacZ gene in murine nasal mucosa.

    PubMed

    Arimoto, Yukiko; Nagata, Hiroshi; Isegawa, Naohisa; Kumahara, Keiichiro; Isoyama, Kyoko; Konno, Akiyoshi; Shirasawa, Hiroshi

    2002-09-01

    Adenovirus is a good tool for transferring exogenous genes into various organs because the virus has a wide spectrum of infection. In this report, we demonstrate that a recombinant adenovirus, Ax1CAlacZ, can transfer an exogenous lacZ gene into murine nasal mucosa in vivo. The efficiency of the exogenous gene expression varied for different cell types and was improved by optimizing the method of administration. In the olfactory region, the olfactory epithelia, sustentacular cells and olfactory nerve efficiently expressed lacZ gene transferred by Ax1CAlacZ using either of two administration methods, dripping or injecting. In contrast, in the respiratory region, the respiratory epithelia but not the subepithelial tissues expressed lacZ gene transferred by Ax1CAlacZ, and the efficiency of the gene transfer, which was low when the virus was administered by nasal drops, was improved when the virus was administered by injection. Our study demonstrated that gene transfer mediated by adenovirus is more efficient in the olfactory epithelia than in the respiratory epithelia, and may be applicable to nasal or paranasal diseases such as olfactory epithelial disturbances. PMID:12403125

  8. Prevalence of Rotavirus, Adenovirus, and Astrovirus Infections among Patients with Acute Gastroenteritis in, Northern Iran

    PubMed Central

    Hamkar, R; Yahyapour, Y; Noroozi, M; Nourijelyani, K; Jalilvand, S; Adibi, L; Vaziri, S; Poor-Babaei, AA; Pakfetrat, A; Savad-Koohi, R

    2010-01-01

    Background: The aim of the study was to determine the incidence of non-bacterial acute gastroenteritis associated with diarrheal diseases in Mazandaran Province, northern Iran. Methods: A total of 400 symptomatic cases from patients with acute gastroenteritis from Mazandaran Province in Iran were screened using EIA method for the presence of rotavirus, adenovirus and astrovirus during 2005–2006. Chi-square tests were used for testing relationships between different variables. Results: Rotavirus, adenovirus and astrovirus were detected in 62%, 2.3%, and 3% of samples, respectively. The maximum rate of rotaviruses was detected in the <1-year-old age group, while minimum rate was found in the 10 years and older age group. Astrovirus and adenovirus were detected predominantly in the 2–5-year-old age group of children, with a prevalence of 8.3% and 3.5% respectively. All studied viral gastroenteritis peaked in the winter, and minimum rate were found in summer. Conclusion: Our statistical analyzes indicated that viral gastroenteritis, especially Rota-viral, had the highest number of occurrences in colder seasons notably in winter and more frequently were observed among younger children. PMID:23113006

  9. Structure of adenovirus bound to cellular receptor car

    DOEpatents

    Freimuth, Paul I.

    2004-05-18

    Disclosed is a mutant adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have significantly weakened binding affinity for CARD1 relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type. In the method, residues of the adenovirus fiber protein knob domain which are predicted to alter D1 binding when mutated, are identified from the crystal structure coordinates of the AD12knob:CAR-D1 complex. A mutation which alters one or more of the identified residues is introduced into the genome of the adenovirus to generate a mutant adenovirus. Whether or not the mutant produced exhibits altered adenovirus-CAR binding properties is then determined.

  10. Crimean-Congo Hemorrhagic Fever (CCHF)

    MedlinePlus

    ... Congo Hemorrhagic Fever (CCHF) [PDF - 2 pages] Virus Ecology Viral Hemorrhagic Fever (VHF) Information for Specific Groups ... Diagnosis Treatment Prevention Outbreak Distribution Map Resources Virus Ecology File Formats Help: How do I view different ...

  11. Quantitative intracerebral brain hemorrhage analysis

    NASA Astrophysics Data System (ADS)

    Loncaric, Sven; Dhawan, Atam P.; Cosic, Dubravko; Kovacevic, Domagoj; Broderick, Joseph; Brott, Thomas

    1999-05-01

    In this paper a system for 3-D quantitative analysis of human spontaneous intracerebral brain hemorrhage (ICH) is described. The purpose of the developed system is to perform quantitative 3-D measurements of the parameters of ICH region and from computed tomography (CT) images. The measured parameter in this phase of the system development is volume of the hemorrhage region. The goal of the project is to measure parameters for a large number of patients having ICH and to correlate measured parameters to patient morbidity and mortality.

  12. Growing Hemorrhagic Choroidal Fissure Cyst

    PubMed Central

    Gelal, Fazıl; Gurkan, Gokhan; Feran, Hamit

    2016-01-01

    Choroidal fissure cysts are often incidentally discovered. They are usually asymptomatic. The authors report a case of growing and hemorrhagic choroidal fissure cyst which was treated surgically. A 22-year-old female presented with headache. Cranial MRI showed a left-sided choroidal fissure cyst. Follow-up MRI showed that the size of the cyst had increased gradually. Twenty months later, the patient was admitted to our emergency department with severe headache. MRI and CT showed an intracystic hematoma. Although such cysts usually have a benign course without symptoms and progression, they may rarely present with intracystic hemorrhage, enlargement of the cyst and increasing symptomatology. PMID:26962426

  13. Symptomatic Tarlov Cyst Following Spontaneous Subarachnoid Hemorrhage

    PubMed Central

    Kong, Woo Keun; Hong, Seung-Koan

    2011-01-01

    Most of Tarlov or perineurial cysts remain asymptomatic throughout the patient's life. The pathogenesis is still unclear. Hemorrhage has been suggested as one of the possible causes and trauma with resultant hemorrhage into subarachnoid space has been suggested as an origin of these cysts. However, Tarlov cysts related to spontaneous subarachnoid hemorrhage has not been reported. The authors report a case of Tarlov cyst which was symptomatic following spontaneous subarachnoid hemorrhage. PMID:22053232

  14. HMGB1 Is a Potential Biomarker for Severe Viral Hemorrhagic Fevers

    PubMed Central

    Resman Rus, Katarina; Fajs, Luka; Korva, Miša; Avšič-Županc, Tatjana

    2016-01-01

    Hemorrhagic fever with renal syndrome (HFRS) and Crimean-Congo hemorrhagic fever (CCHF) are common representatives of viral hemorrhagic fevers still often neglected in some parts of the world. Infection with Dobrava or Puumala virus (HFRS) and Crimean-Congo hemorrhagic fever virus (CCHFV) can result in a mild, nonspecific febrile illness or as a severe disease with hemorrhaging and high fatality rate. An important factor in optimizing survival rate in patients with VHF is instant recognition of the severe form of the disease for which significant biomarkers need to be elucidated. To determine the prognostic value of High Mobility Group Box 1 (HMGB1) as a biomarker for disease severity, we tested acute serum samples of patients with HFRS or CCHF. Our results showed that HMGB1 levels are increased in patients with CCHFV, DOBV or PUUV infection. Above that, concentration of HMGB1 is higher in patients with severe disease progression when compared to the mild clinical course of the disease. Our results indicate that HMGB1 could be a useful prognostic biomarker for disease severity in PUUV and CCHFV infection, where the difference between the mild and severe patients group was highly significant. Even in patients with severe DOBV infection concentrations of HMGB1 were 2.8–times higher than in the mild group, but the difference was not statistically significant. Our results indicated HMGB1 as a potential biomarker for severe hemorrhagic fevers. PMID:27348219

  15. Unique conditionally replication competent bipartite adenoviruses-cancer terminator viruses (CTV): efficacious reagents for cancer gene therapy.

    PubMed

    Sarkar, Devanand; Su, Zao-Zhong; Fisher, Paul B

    2006-07-01

    The frequent resistance of aggressive cancers to currently available therapies, such as radiotherapy and chemotherapy, mandates development of targeted, nontoxic and more efficacious treatment protocols. Conditionally replication competent adenoviruses (CRCAs) that induce oncolysis by cancer-specific replication are currently being evaluated in clinical trials. However, a single modality approach may not be sufficient to completely eradicate cancer in a patient, because most cancers arise from abnormalities in multiple genetic and signal transduction pathways. The promoter region of rodent progression elevated gene-3 (PEG-3), cloned and characterized in our laboratory, embodies the unique property of increased activity in a broad range of tumor cells, both rodent and human, when compared to normal counterparts. Bipartite adenoviruses were engineered to express the E1A gene, necessary for viral replication, under control of the PEG-3 promoter (PEG-Prom) and simultaneously express a second transgene in the E3 region that encodes an apoptosis-inducing and immunomodulatory cytokine, either immune interferon (IFN-gamma) or melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24). These conditionally replication competent bipartite adenoviruses, referred to as cancer terminator viruses (CTVs), facilitated cancer-selective adenovirus replication, robust transgene expression and apoptosis induction with complete eradication of both primary and distant (metastatic) human cancers xenotransplanted in athymic nude mice. These findings suggest that CTVs might prove efficacious for the therapy of primary and advanced neoplastic diseases. PMID:16861924

  16. COINFECTION OF CALIFORNIA SEA LION ADENOVIRUS 1 AND A NOVEL POLYOMAVIRUS IN A HAWAIIAN MONK SEAL (NEOMONACHUS SCHAUINSLANDI).

    PubMed

    Cortés-Hinojosa, Galaxia; Doescher, Bethany; Kinsel, Michael; Lednicky, John; Loeb, Julia; Waltzek, Thomas; Wellehan, James F X

    2016-06-01

    The Hawaiian monk seal (Neomonachus schauinslandi) is an endangered species. Here, we present a clinical case of a 26-yr-old male Hawaiian monk seal (HMS) kept in an aquarium with a history of intermittent anorexia and evidence of renal disease. Histologic examination revealed eosinophilic intranuclear inclusions in the liver. Conventional nested PCR protocols were used to test for viruses, and it tested positive for adenovirus and polyomavirus, and negative for herpesvirus. The adenovirus partial polymerase gene is 100% homologous to that of California sea lion adenovirus 1 (CSLAdV-1). CSLAdV-1 causes viral hepatitis in CSL, and has recently been reported in different species of otariids in an aquarium in Japan ( Otaria flavescens and Arctocephalus pusillus ) and a sequence from Spain has been submitted in NCBI as Otaria flavescens adenovirus-1. The polyomavirus in this animal is a novel virus, and is the first polyomavirus discovered in Hawaiian monk seals. This new virus is designated Hawaiian monk seal polyomavirus (HMSPyV-1), and is 83% homologous to California sea lion Polyomavirus-1 (CSLPyV-1). This is the first report of viral coinfection in a HMS and clinical significance in this case remains unclear but may be associated with advanced age. PMID:27468013

  17. Structure of adenovirus bound to cellular receptor car

    DOEpatents

    Freimuth, Paul I.

    2007-01-02

    Disclosed is a mutant CAR-DI-binding adenovirus which has a genome comprising one or more mutations in sequences which encode the fiber protein knob domain wherein the mutation causes the encoded viral particle to have a significantly weakened binding affinity for CAR-DI relative to wild-type adenovirus. Such mutations may be in sequences which encode either the AB loop, or the HI loop of the fiber protein knob domain. Specific residues and mutations are described. Also disclosed is a method for generating a mutant adenovirus which is characterized by a receptor binding affinity or specificity which differs substantially from wild type.

  18. CT demonstration of bilateral adrenal hemorrhage

    SciTech Connect

    Ling, D.; Korobkin, M.; Silverman, P.M.; Dunnick, N.R.

    1983-08-01

    Bilateral adrenal hemorrhage with subsequent adrenal insufficiency is a recognized complication of anticoagulant therapy. Because the clinical manifestations are often nonspecific, the antemortem diagnosis of adrenal hemorrhage has been a difficult clinical problem. Computed tomography (CT) provides detailed images of the adrenal glands that are not possible with conventional imaging methods. The CT findings of bilateral adrenal hemorrhage in an anticoagulated patient are reported.

  19. New human adenovirus isolated from a renal transplant recipient: description and characterization of candiate adenovirus type 34.

    PubMed Central

    Hierholzer, J C; Atuk, N O; Gwaltney, J M

    1975-01-01

    An antigenically distinct adenovirus is described which was isolated in March 1972 from the urine of a 17-year-old Caucasian male who was experiencing fever after receiving a kidney transplant from a cadaver in February. The adenovirus could not be isolated in April from a pharyngeal swab which yielded cytomegalovirus. Complement-fixation, hemagglutination-inhibition, and/or serum-neutralization tests on sequential serum specimens from the patient confirmed that the adenovirus infection occurred during March and showed that infections with cytomegalovirus and respiratory syncytial virus also occurred during late March and April. The patient's persistent fever, for which other causes could not be found, may have been associated with one or more of these infections. Upper respiratory symptoms and lung involvement were not found during this period. Mild liver dysfunction during this time could not be clearly related to adenovirus infection because of the presence of multiple other causes. The adenovirus may have been latent in the donor kidney and become active in the new host as a consequence of immunological impairment. The adenovirus, purified by terminal dilution and plaque procedures, has antigenic, morphological, biophysical, host susceptibility, and hemagglutinating properties characteristic of adenovirus group IA. Buoyant densities in CsCl are 1.340 g/ml for the virion, 1.304 g/ml for the group CF antigen (hexon), 1.295 g/ml for the major soluble complete hemagglutinin (dodecon), and 1.206 g/ml for the minor soluble complete hemagglutinin (tentatively, fiber dimer). The virus does not cross-react in reciprocal hemagglutination-inhibition and serum-neutralization tests with antisera to adenovirus types 1 to 33. We propose this virus as candidate adenovirus type 34 (Compton). Images PMID:170313

  20. 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

  1. Intraventricular hemorrhage of the newborn

    MedlinePlus

    ... needed to place a tube (shunt) in the brain to drain fluid. Outlook (Prognosis) How well the infant does depends on how premature the baby is and the grade of the hemorrhage. Less than half of babies with lower-grade ... Browse the Encyclopedia A.D. ...

  2. Prolonged abulia following putaminal hemorrhage.

    PubMed

    Nagaratnam, N; Fanella, S; Gopinath, S; Goodwin, A

    2001-01-01

    Abulia, akinetic mutism, and other conditions causing reduced activity and slowness are a continuum of severity of behavior. Unilateral lesions usually cause transient symptoms. This article describes a patient with prolonged abulia lasting 12 weeks after aspontaneous left putaminal hemorrhage. He developed seizures that could be a contributing factor. The pathophysiologic mechanisms are discussed. PMID:17903806

  3. Mechanisms of hemorrhage in dengue without circulatory collapse.

    PubMed

    Krishnamurti, C; Kalayanarooj, S; Cutting, M A; Peat, R A; Rothwell, S W; Reid, T J; Green, S; Nisalak, A; Endy, T P; Vaughn, D W; Nimmannitya, S; Innis, B L

    2001-12-01

    To characterize the molecular basis for the hemostatic defects of dengue infections, a study was conducted in Bangkok, Thailand. Febrile children (n = 68) hospitalized with suspected dengue were enrolled before their clinical syndromes were classified as either dengue fever (DF) or dengue hemorrhagic fever (DHF). Hospital course and outcome were recorded; blood was obtained during the febrile illness (S1), after defervescence (S2), and 1 month after onset of disease (S4). Patients were classified as DF (n = 21) and DHF grades 1, 2, and 3; (DHF1, n = 8; DHF2, n = 30; and DHF3, n = 9). All had marked thrombocytopenia. Bleeding scores were assigned on the basis of bleeding site. Although there was no correlation between bleeding scores and pleural effusion index (a measure of vascular leakage) or bleeding scores and platelet counts, there was a correlation between pleural effusion index and platelet counts. Bleeding scores did not correlate with hemostatic data. Activated partial thromboplastin time was prolonged, with trends toward decreased fibrinogen and increased levels of prothrombin fragment F1.2 in the acute-phase samples. However, no factor level was dramatically decreased. We conclude that most patients with DF or DHF, even without overt hemorrhage, have consumptive coagulopathy. Nevertheless, hemorrhage in dengue without circulatory collapse is most likely due to activation of platelets rather than coagulopathy, which is well compensated. Our data suggest that vascular alteration may be the principal factor involved in the association of thrombocytopenia and hemorrhage with disease severity. PMID:11791984

  4. 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

  5. Hypercoagulability in hereditary hemorrhagic telangiectasia with epilepsy

    PubMed Central

    Finsterer, Josef; Sehnal, Ernst

    2015-01-01

    Recent data indicate that in patients with hereditary hemorrhagic teleangiectasia (HHT), low iron levels due to inadequate replacement after hemorrhagic iron losses are associated with elevated factor-VIII plasma levels and consecutively increased risk of venous thrombo-embolism. Here, we report a patient with HHT, low iron levels, elevated factor-VIII, and recurrent venous thrombo-embolism. A 64-year-old multimorbid Serbian gipsy was diagnosed with HHT at age 62 years. He had a history of recurrent epistaxis, teleangiectasias on the lips, renal and pulmonary arterio-venous malformations, and a family history positive for HHT. He had experienced recurrent venous thrombosis (mesenteric vein thrombosis, portal venous thrombosis, deep venous thrombosis), insufficiently treated with phenprocoumon during 16 months and gastro-intestinal bleeding. Blood tests revealed sideropenia and elevated plasma levels of coagulation factor-VIII. His history was positive for diabetes, arterial hypertension, hyperlipidemia, smoking, cerebral abscess, recurrent ischemic stroke, recurrent ileus, peripheral arterial occluding disease, polyneuropathy, mild renal insufficiency, and epilepsy. Following recent findings, hypercoagulability was attributed to the sideropenia-induced elevation of coagulation factor-VIII. In conclusion, HHT may be associated with hypercoagulability due to elevated factor-VIII associated with low serum iron levels from recurrent bleeding. Iron substitution may prevent HHT patients from hypercoagulability. PMID:26167029

  6. Neurological involvement in hereditary hemorrhagic telangiectasia.

    PubMed

    Labeyrie, Paul-Emile; Courthéoux, Patrick; Babin, Emmanuel; Bergot, Emmanuel; Touzé, Emmanuel; Pelage, Jean-Pierre

    2016-07-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant disorder characterized by epistaxis, telangiectases, and multi-organ vascular dysplasia. Head and neck localizations of HHT are recurrent, frequent associated with serious complications. The aim of this study was to describe the clinical and imaging patterns of neurological involvement in HHT and to discuss the role of interventional radiology in the management of HHT patients. Based on a multidisciplinary experience of twenty years at our center, we report here the different aspects of neurological involvement of HHT. Depending on the genetic type of the disease, vascular abnormalities may affect different organs. The knowledge of neurological involvement according to specific localization of HHT makes detection easier. As cerebral or spinal arteriovenous fistula may be present in patients with epistaxis or pulmonary arteriovenous malformations (PAVMs), radiologists should be able to detect high-risk lesions and prevent related complications. Finally, we review indications and techniques of embolization for hemorrhagic lesions and emphasize that endovascular therapies are very effective and safe in experienced hands. Head and neck imaging is commonly used for the diagnosis of HHT. Imaging plays also a key role for patient evaluation before treatment as pluridisciplinary management is needed. PMID:27059009

  7. Massive suprachoroidal hemorrhage: Surgical management and outcome

    PubMed Central

    Laube, Thomas; Brockmann, Claudia; Bornfeld, Norbert

    2015-01-01

    Objective: To describe options for vitreoretinal surgery in the management of massive suprachoroidal hemorrhage (SCH). Methods: Visual acuity (VA), ocular findings, timing of surgical intervention, surgical procedures, and outcomes of four patients diagnosed with massive SCH and admitted to the University Eye Clinic Essen were reviewed retrospectively. Results: Four eyes of four patients (mean age, 82 years; range, 74–89 years) were studied. In three cases the occurrence of SCH was related to cataract surgery and occurred intra- or postoperatively. One patient developed spontaneous SCH of unclear origin. Three patients had a history of arterial hypertension; one eye had high myopia, two patients suffered from cardiovascular diseases, and two patients had glaucoma. Postoperative follow up of the patients ranged from 5 to 29.5 months (mean, 19.6 months). Transscleral drainage of SCH was in all cases combined with pars plana vitrectomy, use of heavy liquids (perfluorodecalin) and silicone oil tamponade. The mean time interval from hemorrhage to surgical intervention was 16.5 days (range 5–29 days). Preoperative VA of all eyes was light perception. Two patients achieved a final postoperative visual acuity of 20/20 and 20/320, respectively, one patient improved to hand motion, and one patient resulted in no light perception. Conclusions: Surgical interventions including transscleral drainage of SCH, vitrectomy, and silicone oil tamponade are valuable options in the management of massive SCH to save the eye and possibly improve the otherwise extreme poor prognosis.

  8. Hypercoagulability in hereditary hemorrhagic telangiectasia with epilepsy.

    PubMed

    Finsterer, Josef; Sehnal, Ernst

    2015-01-01

    Recent data indicate that in patients with hereditary hemorrhagic teleangiectasia (HHT), low iron levels due to inadequate replacement after hemorrhagic iron losses are associated with elevated factor-VIII plasma levels and consecutively increased risk of venous thrombo-embolism. Here, we report a patient with HHT, low iron levels, elevated factor-VIII, and recurrent venous thrombo-embolism. A 64-year-old multimorbid Serbian gipsy was diagnosed with HHT at age 62 years. He had a history of recurrent epistaxis, teleangiectasias on the lips, renal and pulmonary arterio-venous malformations, and a family history positive for HHT. He had experienced recurrent venous thrombosis (mesenteric vein thrombosis, portal venous thrombosis, deep venous thrombosis), insufficiently treated with phenprocoumon during 16 months and gastro-intestinal bleeding. Blood tests revealed sideropenia and elevated plasma levels of coagulation factor-VIII. His history was positive for diabetes, arterial hypertension, hyperlipidemia, smoking, cerebral abscess, recurrent ischemic stroke, recurrent ileus, peripheral arterial occluding disease, polyneuropathy, mild renal insufficiency, and epilepsy. Following recent findings, hypercoagulability was attributed to the sideropenia-induced elevation of coagulation factor-VIII. In conclusion, HHT may be associated with hypercoagulability due to elevated factor-VIII associated with low serum iron levels from recurrent bleeding. Iron substitution may prevent HHT patients from hypercoagulability. PMID:26167029

  9. The Intracellular Domain of the Coxsackievirus and Adenovirus Receptor Differentially Influences Adenovirus Entry

    PubMed Central

    Loustalot, Fabien

    2015-01-01

    ABSTRACT The coxsackievirus and adenovirus receptor (CAR) is a cell adhesion molecule used as a docking molecule by some adenoviruses (AdVs) and group B coxsackieviruses. We previously proposed that the preferential transduction of neurons by canine adenovirus type 2 (CAV-2) is due to CAR-mediated internalization. Our proposed pathway of CAV-2 entry is in contrast to that of human AdV type 5 (HAdV-C5) in nonneuronal cells, where internalization is mediated by auxiliary receptors such as integrins. We therefore asked if in fibroblast-like cells the intracellular domain (ICD) of CAR plays a role in the internalization of the CAV-2 fiber knob (FKCAV), CAV-2, or HAdV-C5 when the capsid cannot engage integrins. Here, we show that in fibroblast-like cells, the CAR ICD is needed for FKCAV entry and efficient CAV-2 transduction but dispensable for HAdV-C5 and an HAdV-C5 capsid lacking the RGD sequence (an integrin-interacting motif) in the penton. Moreover, the deletion of the CAR ICD further impacts CAV-2 intracellular trafficking, highlighting the crucial role of CAR in CAV-2 intracellular dynamics. These data demonstrate that the CAR ICD contains sequences important for the recruitment of the endocytic machinery that differentially influences AdV cell entry. IMPORTANCE Understanding how viruses interact with the host cell surface and reach the intracellular space is of crucial importance for applied and fundamental virology. Here, we compare the role of a cell adhesion molecule (CAR) in the internalization of adenoviruses that naturally infect humans and Canidae. We show that the intracellular domain of CAR differentially regulates AdV entry and trafficking. Our study highlights the mechanistic differences that a receptor can have for two viruses from the same family. PMID:26136571

  10. [A case of Churg-Strauss syndrome with subarachnoid hemorrhage].

    PubMed

    Ito, Miiko; Kato, Naoki; Su, Ching-Chan; Kayama, Takamasa

    2014-03-01

    Churg-Strauss syndrome (CSS) is a vasculitis syndromes and is only rarely complicated by subarachnoid hemorrhage. In the current report, we describe a case of CSS with subarachnoid hemorrhage, which showed a favorable outcome following conservative treatment. A 68-year-old man with CSS on maintenance steroid therapy underwent MRI/A during tinnitus aggravation, and showed dilation of the left middle cerebral artery and stenosis of the peripheral area of the right vertebral artery. After 2 months, he presented sudden pain in the occipitocervical area, and CT revealed subarachnoid hemorrhage. Intracranial 3D CT-A and MRI/A showed the development of a protrusion at the base of the left anterior cerebral artery. Although both findings suggested cerebral artery dissection, the source of hemorrhage could not be identified. The 2009 Japanese Guidelines for the Management of Stroke recommends early diagnosis and treatment of hemorrhagic cerebral artery dissection because of the high risk of re-bleeding. However, considering the risks of vasculitis aggravation, development of systemic complications, and recurrence, conservative treatment was selected. In addition, owing to the risk of complications associated with the frequent use of iodinated contrast agents and angiography procedures, patient was followed up using MRI. His course was favorable, and he was discharged despite mild right abducens paralysis. When patients with hemorrhagic cerebral artery dissection have a history of allergic diseases, CCS should be considered; conservative treatment consisting of rest, strict blood pressure control, and steroid therapy may be the most appropriate option for certain patients. PMID:24607952

  11. Structure and Sialyllactose Binding of the Carboxy-Terminal Head Domain of the Fibre from a Siadenovirus, Turkey Adenovirus 3

    PubMed Central

    Singh, Abhimanyu K.; Berbís, M. Álvaro; Ballmann, Mónika Z.; Kilcoyne, Michelle; Menéndez, Margarita; Nguyen, Thanh H.; Joshi, Lokesh; Cañada, F. Javier; Jiménez-Barbero, Jesús; Benkő, Mária; Harrach, Balázs; van Raaij, Mark J.

    2015-01-01

    The virulent form of turkey adenovirus 3 (TAdV-3), also known as turkey hemorrhagic enteritis virus (THEV), is an economically important poultry pathogen, while the avirulent form is used as a vaccine. TAdV-3 belongs to the genus Siadenovirus. The carboxy-terminal region of its fibre does not have significant sequence similarity to any other adenovirus fibre heads of known structure. Two amino acid sequence differences between virulent and avirulent TAdV-3 map on the fibre head: where virulent TAdV-3 contains Ile354 and Thr376, avirulent TAdV-3 contains Met354 and Met376. We determined the crystal structures of the trimeric virulent and avirulent TAdV-3 fibre head domains at 2.2 Å resolution. Each monomer contains a beta-sandwich, which, surprisingly, resembles reovirus fibre head more than other adenovirus fibres, although the ABCJ-GHID topology is conserved in all. A beta-hairpin insertion in the C-strand of each trimer subunit embraces its neighbouring monomer. The avirulent and virulent TAdV-3 fibre heads are identical apart from the exact orientation of the beta-hairpin insertion. In vitro, sialyllactose was identified as a ligand by glycan microarray analysis, nuclear magnetic resonance spectroscopy, and crystallography. Its dissociation constant was measured to be in the mM range by isothermal titration calorimetry. The ligand binds to the side of the fibre head, involving amino acids Glu392, Thr419, Val420, Lys421, Asn422, and Gly423 binding to the sialic acid group. It binds slightly more strongly to the avirulent form. We propose that, in vivo, the TAdV-3 fibre may bind a sialic acid-containing cell surface component. PMID:26418008

  12. Structure and Sialyllactose Binding of the Carboxy-Terminal Head Domain of the Fibre from a Siadenovirus, Turkey Adenovirus 3.

    PubMed

    Singh, Abhimanyu K; Berbís, M Álvaro; Ballmann, Mónika Z; Kilcoyne, Michelle; Menéndez, Margarita; Nguyen, Thanh H; Joshi, Lokesh; Cañada, F Javier; Jiménez-Barbero, Jesús; Benkő, Mária; Harrach, Balázs; van Raaij, Mark J

    2015-01-01

    The virulent form of turkey adenovirus 3 (TAdV-3), also known as turkey hemorrhagic enteritis virus (THEV), is an economically important poultry pathogen, while the avirulent form is used as a vaccine. TAdV-3 belongs to the genus Siadenovirus. The carboxy-terminal region of its fibre does not have significant sequence similarity to any other adenovirus fibre heads of known structure. Two amino acid sequence differences between virulent and avirulent TAdV-3 map on the fibre head: where virulent TAdV-3 contains Ile354 and Thr376, avirulent TAdV-3 contains Met354 and Met376. We determined the crystal structures of the trimeric virulent and avirulent TAdV-3 fibre head domains at 2.2 Å resolution. Each monomer contains a beta-sandwich, which, surprisingly, resembles reovirus fibre head more than other adenovirus fibres, although the ABCJ-GHID topology is conserved in all. A beta-hairpin insertion in the C-strand of each trimer subunit embraces its neighbouring monomer. The avirulent and virulent TAdV-3 fibre heads are identical apart from the exact orientation of the beta-hairpin insertion. In vitro, sialyllactose was identified as a ligand by glycan microarray analysis, nuclear magnetic resonance spectroscopy, and crystallography. Its dissociation constant was measured to be in the mM range by isothermal titration calorimetry. The ligand binds to the side of the fibre head, involving amino acids Glu392, Thr419, Val420, Lys421, Asn422, and Gly423 binding to the sialic acid group. It binds slightly more strongly to the avirulent form. We propose that, in vivo, the TAdV-3 fibre may bind a sialic acid-containing cell surface component. PMID:26418008

  13. Transient acute adrenal insufficiency associated with adenovirus serotype 40 infection

    PubMed Central

    Rai, Birendra; Ali, Muhammad; Kumar, Varun; Krebit, Ibraheem

    2014-01-01

    We present an instance of a 6-year-old boy who was admitted with adenovirus infection and developed transient acute adrenal insufficiency, which required supplementation with glucocorticoids and mineralocorticoids for 8 weeks. Adenovirus has got adrenotropic potential and can cause adrenal insufficiency. We could not find any similar reported case in medical literature. We hope our case would add to the existing knowledge of adenoviral complications in paediatric patients. PMID:24928932

  14. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus.

    PubMed

    Matoq, Amr; Salahuddin, Asma

    2016-01-01

    Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection. PMID:27340581

  15. Acute Hepatitis and Pancytopenia in Healthy Infant with Adenovirus

    PubMed Central

    Salahuddin, Asma

    2016-01-01

    Adenoviruses are a common cause of respiratory infection, pharyngitis, and conjunctivitis in infants and young children. They are known to cause hepatitis and liver failure in immunocompromised patients; they are a rare cause of hepatitis in immunocompetent patients and have been known to cause fulminant hepatic failure. We present a 23-month-old immunocompetent infant who presented with acute noncholestatic hepatitis, hypoalbuminemia, generalized anasarca, and pancytopenia secondary to adenovirus infection. PMID:27340581

  16. The relative magnitude of transgene-specific adaptive immune responses induced by human and chimpanzee adenovirus vectors differs between laboratory animals and a target species.

    PubMed

    Dicks, Matthew D J; Guzman, Efrain; Spencer, Alexandra J; Gilbert, Sarah C; Charleston, Bryan; Hill, Adrian V S; Cottingham, Matthew G

    2015-02-25

    Adenovirus vaccine vectors generated from new viral serotypes are routinely screened in pre-clinical laboratory animal models to identify the most immunogenic and efficacious candidates for further evaluation in clinical human and veterinary settings. Here, we show that studies in a laboratory species do not necessarily predict the hierarchy of vector performance in other mammals. In mice, after intramuscular immunization, HAdV-5 (Human adenovirus C) based vectors elicited cellular and humoral adaptive responses of higher magnitudes compared to the chimpanzee adenovirus vectors ChAdOx1 and AdC68 from species Human adenovirus E. After HAdV-5 vaccination, transgene specific IFN-γ(+) CD8(+) T cell responses reached peak magnitude later than after ChAdOx1 and AdC68 vaccination, and exhibited a slower contraction to a memory phenotype. In cattle, cellular and humoral immune responses were at least equivalent, if not higher, in magnitude after ChAdOx1 vaccination compared to HAdV-5. Though we have not tested protective efficacy in a disease model, these findings have important implications for the selection of candidate vectors for further evaluation. We propose that vaccines based on ChAdOx1 or other Human adenovirus E serotypes could be at least as immunogenic as current licensed bovine vaccines based on HAdV-5. PMID:25629523

  17. Primary Bovine Intervertebral Disc Cells Transduced with Adenovirus Overexpressing 12 BMPs and Sox9 Maintain Appropriate Phenotype

    PubMed Central

    Zhang, Yejia; Markova, Dessislava; Im, Hee-Jeong; Hu, Wenyang; Thonar, Eugene J.-M.A.; He, Tong-Chuan; An, Howard S.; Phillips, Frank M.; Anderson, D. Greg

    2010-01-01

    Objective To confirm that primary intervertebral disc cells cultured in monolayer transduced with adenovirus maintained their phenotype, hence is an appropriate system to test gene therapy agents. Design Adult bovine nucleus pulposus and anulus fibrosus cells cultured in monolayer were transduced with adenoviruses expressing human bone morphogenetic proteins (AdBMPs) or Sox9 (AdSox9), or green fluorescence protein (AdGFP, as control). Chondrocyte phenotypic markers (e.g., type II collagen and aggrecan) and the chondrocyte hypertrophy marker (type X collagen) were measured 6 days after viral transduction by reverse-transcription polymerase chain reaction. Results Primary nucleus pulposus and anulus fibrosus cells transduced with AdBMPs, AdSox9, or adenovirus-expressing green fluorescence protein only (AdGFP, as control) continue to express healthy chondrocyte phenotypic markers and showed no evidence of the expression of the chondrocyte hypertrophy marker (type X collagen gene). Thus, we have shown that bovine nucleus pulposus and anulus fibrosus cells transduced with adenovirus overexpressing 12 different bone morphogenetic proteins or Sox9 maintain their phenotype in short-term culture. Conclusions In this study, primary bovine intervertebral disc cells transduced with adenovirus overexpressing 12 bone morphogenetic proteins or Sox9 preserved their phenotype in short-term culture. These cells did not express the type X collagen gene, an undesirable chondrocyte hypertrophic gene that could lead to ossification. Therefore, low-passage intervertebral disc cells cultured in monolayer is an appropriate culture system to test therapeutic genes. We further suggest that these cells may also be appropriate for engineering tissues or for cell therapy for degenerative disc diseases. PMID:19454853

  18. Acute hemorrhagic leukoencephalitis (Weston-Hurst syndrome) in a patient with relapse-remitting multiple sclerosis.

    PubMed

    Yildiz, Özlem; Pul, Refik; Raab, Peter; Hartmann, Christian; Skripuletz, Thomas; Stangel, Martin

    2015-01-01

    Acute hemorrhagic leukoencephalitis is a fulminant demyelinating disease and commonly considered as a rare and severe variant of acute disseminated encephalomyelitis. Here, we report the clinical, magnetic resonance imaging, and brain biopsy findings of a 35-year-old female with relapsing-remitting multiple sclerosis, who developed acute hemorrhagic leukoencephalitis. Magnetic resonance imaging revealed symmetrical hemorrhagic lesions in the basal ganglia including the thalami. Disease progression was consistent with acute hemorrhagic leukoencephalitis with rapid deterioration of consciousness and seizures. Besides hemorrhage, infiltration of neutrophils was detected in brain biopsy.Acute hemorrhagic leukoencephalitis, also known as Weston-Hurst syndrome, is an excessive immunological response of unknown etiology. So far, an association with multiple sclerosis has not been reported. The present case raises the question, whether acute hemorrhagic leukoencephalitis is a specific hyperacute form of acute disseminated encephalomyelitis, a severe and unspecific form of an immune response in the central nervous system, or belongs to the spectrum of tumefactive multiple sclerosis. PMID:26376717

  19. Polymeric oncolytic adenovirus for cancer gene therapy

    PubMed Central

    Choi, Joung-Woo; Lee, Young Sook; Yun, Chae-Ok; Kim, Sung Wan

    2015-01-01

    Oncolytic adenovirus (Ad) vectors present a promising modality to treat cancer. Many clinical trials have been done with either naked oncolytic Ad or combination with chemotherapies. However, the systemic injection of oncolytic Ad in clinical applications is restricted due to significant liver toxicity and immunogenicity. To overcome these issues, Ad has been engineered physically or chemically with numerous polymers for shielding the Ad surface, accomplishing extended blood circulation time and reduced immunogenicity as well as hepatotoxicity. In this review, we describe and classify the characteristics of polymer modified oncolytic Ad following each strategy for cancer treatment. Furthermore, this review concludes with the highlights of various polymer-coated Ads and their prospects, and directions for future research. PMID:26453806

  20. Adenovirus infection of the large bowel in HIV positive patients.

    PubMed Central

    Maddox, A.; Francis, N.; Moss, J.; Blanshard, C.; Gazzard, B.

    1992-01-01

    AIMS: To describe the microscopic appearance of adenovirus infection in the large bowel of human immunodeficiency virus (HIV) positive patients with diarrhoea. METHODS: Large bowel biopsy specimens from 10 HIV positive patients, eight of whom were also infected with other gastrointestinal pathogens, with diarrhoea were examined, together with six small bowel biopsy specimens from the same group of patients. Eight of the patients had AIDS. The biopsy specimens were examined by light microscopy performed on haematoxylin and eosin stained and immunoperoxidase preparations, the latter using a commercially available antibody (Serotec MCA 489). Confirmation was obtained with electron microscopy. RESULTS: The morphological appearance of cells infected with adenovirus showed characteristic nuclear and cellular changes, although the inflammatory reaction was non-specific. Immunoperoxidase staining for adenovirus was sensitive and specific, and the presence of viral inclusions consistent with adenovirus was confirmed by electron microscopy. CONCLUSIONS: The light microscopic features of adenovirus infection are distinctive and immunocytochemistry with a commercially available antibody is a sensitive and specific means of confirming the diagnosis. Further studies of the role of adenovirus in causing diarrhoea in these patients are indicated. Images PMID:1401177

  1. Surgery for Patients With Spontaneous Deep Supratentorial Intracerebral Hemorrhage

    PubMed Central

    Zheng, Jun; Li, Hao; Zhao, He-Xiang; Guo, Rui; Lin, Sen; Dong, Wei; Ma, Lu; Fang, Yuan; Tian, Meng; Liu, Ming; You, Chao

    2016-01-01

    Abstract Spontaneous intracerebral hemorrhage (sICH) is one of the most dangerous cerebrovascular diseases, especially when in deep brain. The treatment of spontaneous deep supratentorial intracerebral hemorrhage is still controversial. We conducted a retrospective case-control study using propensity score matching to compare the efficacy of surgery and conservative treatment for patients with deep surpatentorial hemorrhage. We observed the outcomes of consecutive patients with spontaneous deep supratentorial hemorrhage retrospectively from December 2008 to July 2013. Clinical outcomes of surgery and conservative treatments were compared in patients with deep sICH using propensity score matching method. The primary outcome was neurological function status at 6 months post ictus. The second outcomes included mortality at 30 days and 6 months, and the incidence of complications. Subgroup analyses of 6-month outcome were conducted. Sixty-three (22.66%) of the 278 patients who received surgery had a favorable neurological function status at 6 months, whereas in the conservative group, 66 of 278 (23.74%) had the same result (P = 0.763). The 30-day mortality in the surgical group was 19.06%, whereas 30.58% in the conservative group (P = 0.002). There was significant difference in the mortality at 6 months after ictus as well (23.38% vs 36.33%, P = 0.001). The subgroup analyses showed significantly better outcomes for the surgical group when hematoma was >40 mL (13.33% vs 0%, P = 0.005) or complicated with intraventricular hemorrhage (16.67% vs 7.27%, P = 0.034). For complications, the risk of pulmonary infection, gastrointestinal hemorrhage, urinary infection, pulmonary embolus, and need for tracheostomy/long term ventilation in the surgical group was higher than the conservative group (31.29% vs 15.47%, P < 0.001; 6.83% vs 3.96%, P = 0.133; 2.88% vs 1.80%, P = 0.400; 1.80% vs 1.08%, P = 0.476; 32.73% vs 23.38%, P = 0

  2. Intraventricular hemorrhage expansion in patients with spontaneous intracerebral hemorrhage

    PubMed Central

    Witsch, Jens; Bruce, Eliza; Meyers, Emma; Velazquez, Angela; Schmidt, J. Michael; Suwatcharangkoon, Sureerat; Agarwal, Sachin; Park, Soojin; Falo, M. Cristina; Connolly, E. Sander

    2015-01-01

    Objective: To evaluate whether delayed appearance of intraventricular hemorrhage (dIVH) represents an independent entity from intraventricular hemorrhage (IVH) present on admission CT or is primarily related to the time interval between symptom onset and admission CT. Methods: A total of 282 spontaneous intracerebral hemorrhage (ICH) patients, admitted February 2009–March 2014 to the neurological intensive care unit of a tertiary care university hospital, were prospectively enrolled in the ICH Outcomes Project. Multivariate logistic regression was used to determine associations with acute mortality and functional long-term outcome (modified Rankin Scale). Results: A cohort of 282 ICH patients was retrospectively studied: 151 (53.5%) had intraventricular hemorrhage on initial CT scan (iIVH). Of the remaining 131 patients, 19 (14.5%) developed IVH after the initial CT scan (dIVH). The median times from symptom onset to admission CT were 1.1, 6.0, and 7.4 hours for the dIVH, iIVH, and no IVH groups (Mann-Whitney U test, dIVH vs iIVH, p < 0.001) and median time from onset to dIVH detection was 7.2 hours. The increase in ICH volume following hospital admission was larger in dIVH than in iIVH and no IVH patients (mean 17.6, 0.2, and 0.4 mL). After controlling for components of the ICH score and hematoma expansion, presence of IVH on initial CT was associated with discharge mortality and poor outcome at 3, 6, and 12 months, but dIVH was not associated with any of the outcome measures. Conclusions: In ICH patients, associated IVH on admission imaging is commonly encountered and is associated with poor long-term outcome. In contrast, dIVH on subsequent scans is far less common and does not appear to portend worse outcome. PMID:25663233

  3. Embolization for Treatment of Gastrointestinal Hemorrhage Secondary to Recurrent Renal Cell Carcinoma

    SciTech Connect

    Kobak, Jeff; Gandras, Eric J. Fleury, Linwald; Macura, Jerzy; Shams, Joseph

    2006-12-15

    Massive gastrointestinal hemorrhage secondary to metastatic renal cell carcinoma involving the jejunum is rare but has been previously described in the medical literature. Treatment options for metastatic renal cell carcinoma are limited, but transcatheter arterial embolization can be performed to control gastrointestinal hemorrhage either alone or prior to surgical resection. We describe a case of successful transcatheter arterial embolization for control of massive gastrointestinal hemorrhage secondary to locally recurrent renal cell carcinoma invading the jejunum and review the literature. Arteriography provided both the diagnosis of recurrent disease and the means of therapy.

  4. An Unusual Case of Crimean Congo Hemorrhagic Fever: Prolonged Bleeding with Successful Recovery.

    PubMed

    Hussain, Qurban; Shaikh, Bilal Hussain; Bhutto, Ali Raza; Sohaib, Muneebah

    2016-02-01

    Crimean Congo Hemorrhagic Fever (CCHF) is a tick-borne viral disease with a major reservoir in both domestic and wild animals. In Pakistan, it is endemic largely in rural areas and most cases occur in spring and autumn. Recently, cases are being reported throughout the year, including winter months, with some even from urban areas. Death from CCHF is most likely to occur during the hemorrhagic phase. We report a case presenting from an urban locality in December. Clinical presentation was characterized by a prolonged hemorrhagic phase and a delayed normalization of platelet counts. PMID:26876406

  5. Epidemiology and Pathogenesis of Bolivian Hemorrhagic Fever

    PubMed Central

    Patterson, Michael; Grant, Ashley; Paessler, Slobodan

    2014-01-01

    The etiologic agent of Bolivian hemorrhagic fever (BHF), Machupo virus (MACV) is reported to have a mortality rate of 25 to 35%. First identified in 1959, BHF was the cause of a localized outbreak in San Joaquin until rodent population controls were implemented in 1964. The rodent Calomys collosus was identified as the primary vector and reservoir for the virus. Multiple animal models were considered during the 1970’s with the most human-like disease identified in Rhesus macaques but minimal characterization of the pathogenesis has been published since. A reemergence of reported BHF cases has been reported in recent years, which necessitates the further study and development of a vaccine to prevent future outbreaks. PMID:24636947

  6. Rejection of adenovirus infection is independent of coxsackie and adenovirus receptor expression in cisplatin-resistant human lung cancer cells.

    PubMed

    Zhang, Nian-Hua; Peng, Rui-Qing; Ding, Ya; Zhang, Xiao-Shi

    2016-08-01

    The adenovirus vector-based cancer gene therapy is controversial. Low transduction efficacy is believed to be one of the main barriers for the decreased expression of coxsackie and adenovirus receptor (CAR) on tumor cells. However, the expression of CAR on primary tumor tissue and tumor tissue survived from treatment has still been not extensively studied. The present study analyzed the adenovirus infection rates and CAR expression in human lung adenocarcinoma cell line A549 and its cisplatin-resistant subline A549/DDP. The results showed that although the CAR expression in A549 and A549/DDP was not different, compared with the A549, A549/DDP appeared obviously to reject adenovirus infection. Moreover, we modified CAR expression in the two cell lines with proteasome inhibitor MG-132 and histone deacetylase inhibitor trichostatin A (TSA), and analyzed the adenovirus infection rates after modifying agent treatments. Both TSA and MG-132 pretreatments could increase the CAR expression in the two cell lines, but the drug pretreatments could only make A549 cells more susceptible to adenovirus infectivity. PMID:27373420

  7. Human Adenovirus 52 Uses Sialic Acid-containing Glycoproteins and the Coxsackie and Adenovirus Receptor for Binding to Target Cells

    PubMed Central

    Lenman, Annasara; Liaci, A. Manuel; Liu, Yan; Årdahl, Carin; Rajan, Anandi; Nilsson, Emma; Bradford, Will; Kaeshammer, Lisa; Jones, Morris S.; Frängsmyr, Lars; Feizi, Ten; Stehle, Thilo; Arnberg, Niklas

    2015-01-01

    Most adenoviruses attach to host cells by means of the protruding fiber protein that binds to host cells via the coxsackievirus and adenovirus receptor (CAR) protein. Human adenovirus type 52 (HAdV-52) is one of only three gastroenteritis-causing HAdVs that are equipped with two different fiber proteins, one long and one short. Here we show, by means of virion-cell binding and infection experiments, that HAdV-52 can also attach to host cells via CAR, but most of the binding depends on sialylated glycoproteins. Glycan microarray, flow cytometry, surface plasmon resonance and ELISA analyses reveal that the terminal knob domain of the long fiber (52LFK) binds to CAR, and the knob domain of the short fiber (52SFK) binds to sialylated glycoproteins. X-ray crystallographic analysis of 52SFK in complex with 2-O-methylated sialic acid combined with functional studies of knob mutants revealed a new sialic acid binding site compared to other, known adenovirus:glycan interactions. Our findings shed light on adenovirus biology and may help to improve targeting of adenovirus-based vectors for gene therapy. PMID:25674795

  8. Gastrointestinal hemorrhage: evaluation with MDCT.

    PubMed

    Soto, Jorge A; Park, Seong Ho; Fletcher, Joel G; Fidler, Jeff L

    2015-06-01

    Gastrointestinal (GI) bleeding is a common medical problem, with high associated morbidity and mortality. The clinical presentation of gastrointestinal hemorrhage varies with the location of the bleeding source, the intensity of the bleed, and the presence of comorbidities that affect the ability to tolerate blood loss. Conventional endoscopic examinations are usually the initial diagnostic tests in patients presenting with overt gastrointestinal hemorrhage. However, implementation of upper tract endoscopy and colonoscopy in the emergency setting can be challenging due to inconsistent availability of the service and difficulties in achieving adequate colonic cleansing in emergent situations. Thus, imaging tests are often relied upon to establish the location and the cause of bleeding, either for initial diagnosis or after non-revealing upper and lower tract endoscopies ("obscure" bleeding). This article discusses the imaging evaluation of patients with gastrointestinal bleeding and reviews the imaging appearance of the most common causes, taking into account the two most relevant clinical presentations: overt bleeding and obscure bleeding. PMID:25637128

  9. A Novel Polyomavirus (Goose Hemorrhagic Polyomavirus) Is the Agent of Hemorrhagic Nephritis Enteritis of Geese

    PubMed Central

    Guerin, Jean-Luc; Gelfi, Jacqueline; Dubois, Luc; Vuillaume, Aimé; Boucraut-Baralon, Corine; Pingret, Jean-Luc

    2000-01-01

    We have identified the etiological agent of hemorrhagic nephritis enteritis of geese (HNEG), a fatal disease of European geese. HNEG has been recognized in almost all goose breeding areas, with an epizootic pattern, and up to now, the infectious agent has remained unknown. In order to identify the causative agent, infected tissues from HNEG-affected geese were inoculated to 1-day-old goslings, which then developed clinical signs typical of HNEG. Tissue homogenates from these birds were subjected to Freon extraction followed by sucrose density gradient ultracentrifugation. The resulting main band was examined by electron microscopy and consisted of spherical, naked, papovavirus-like particles approximately 45 nm in diameter. The virus was isolated and propagated in goose kidney cell primary culture. Tissue- or culture-purified virus allowed the experimental reproduction of the disease in goslings. Random PCR amplification of viral nucleic acid produced a 1,175-bp fragment which was shown to be associated with field samples collected from geese affected by HNEG on commercial farms in France. Sequence analysis of the PCR product revealed a unique open reading frame, showing 63 to 72% amino acid similarity with the major capsid protein (VP1) of several polyomaviruses. Finally, based on phylogenetic analysis, we conclude that the causative agent of HNEG is closely related to but clearly distinct from other polyomaviruses; we thus have named this newly identified virus Goose hemorrhagic polyomavirus. PMID:10775588

  10. Acute suprachoroidal hemorrhage during phacoemulsification.

    PubMed

    Nambiar, A K; Fox, P D

    2000-06-01

    We present a case of acute suprachoroidal hemorrhage that developed during routine phacoemulsification in an 85-year-old patient after uneventful administration of periocular anesthesia. Pre-existing risk factors included advanced age, glaucoma, myopia, and hypertension. The scleral tunnel prevented major expulsion of intraocular contents; however, raised intraocular pressure prevented intraocular lens implantation. The rarity of this condition raises questions regarding the further management and precautions related to it. PMID:10889443

  11. Crimean-Congo hemorrhagic fever (CCHF) in Southern Kordofan

    PubMed Central

    Taha, Mohamed Ahmed

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is a disease that poses a great threat to public health owing to its high mortality rate (30-70%), mode of transmission and geographic distribution. Here, we report on a nine years-old Sudanese boy from Southern Kordofan State who presented with Jaundice, high-grade fever, severe headache, abdominal pain and a history of hematemesis. The diagnosis of CCHF was confirmed based on clinical and serological findings. PMID:27493394

  12. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... dilution in a varying serum-constant virus neutralization test using 50 to 300 TCID50 of canine adenovirus... virus neutralization test using 50 to 300 TCID50 of canine adenovirus. (i) A geometric mean titer of...

  13. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... dilution in a varying serum-constant virus neutralization test using 50 to 300 TCID50 of canine adenovirus... virus neutralization test using 50 to 300 TCID50 of canine adenovirus. (i) A geometric mean titer of...

  14. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... dilution in a varying serum-constant virus neutralization test using 50 to 300 TCID50 of canine adenovirus... virus neutralization test using 50 to 300 TCID50 of canine adenovirus. (i) A geometric mean titer of...

  15. SCREENING STUDIES TO DETRMINE THE EFFECTIVENESS OF CHLORINE TO INACTIVATE ADENOVIRUS (RM.C.M.4)

    EPA Science Inventory

    To evaluate the susceptibility of adenovirus (CCL organism) to inactivation by chemical disinfectants, including chlorine and chloramine. Bench scale disinfection studies will be conducted on adenovirus and selected bacteriophages suspended in oxidant demand free buffered water: ...

  16. Rodent neonatal germinal matrix hemorrhage mimics the human brain injury, neurological consequences, and post-hemorrhagic hydrocephalus

    PubMed Central

    Lekic, Tim; Manaenko, Anatol; Rolland, William; Krafft, Paul R.; Peters, Regina; Hartman, Richard E.; Altay, Orhan; Tang, Jiping; Zhang, John H.

    2012-01-01

    Germinal matrix hemorrhage (GMH) is the most common neurological disease of premature newborns. GMH causes neurological sequelae such as cerebral palsy, post-hemorrhagic hydrocephalus, and mental retardation. Despite this, there is no standardized animal model of spontaneous GMH using newborn rats to depict the condition. We asked whether stereotactic injection of collagenase type VII (0.3 U) into the ganglionic eminence of neonatal rats would reproduce the acute brain injury, gliosis, hydrocephalus, periventricular leukomalacia, and attendant neurological consequences found in humans. To test this hypothesis, we used our neonatal rat model of collagenase-induced GMH in P7 pups, and found that the levels of free-radical adducts (nitrotyrosine and 4-hyroxynonenal), proliferation (mammalian target of rapamycin), inflammation (COX-2), blood components (hemoglobin and thrombin), and gliosis (vitronectin and GFAP) were higher in the forebrain of GMH pups, than in controls. Neurobehavioral testing showed that pups with GMH had developmental delay, and the juvenile animals had significant cognitive and motor disability, suggesting clinical relevance of the model. There was also evidence of white-matter reduction, ventricular dilation, and brain atrophy in the GMH animals. This study highlights an instructive animal model of the neurological consequences after germinal matrix hemorrhage, with evidence of brain injuries that can be used to evaluate strategies in the prevention and treatment of post-hemorrhagic complications. PMID:22524990

  17. [Familial brain abscess as a complication of hereditary hemorrhagic telangiectasia].

    PubMed

    Szöts, M; Szapáry, L; Nagy, F; Vetö, F

    2001-10-21

    The hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber disease) is an inherited autosomal dominant disease with angiodysplasia of the skin, mucosa, parenchymal organs, and it can affect the central nervous system. In 40% of the cases neurological complications, most frequently intracerebral abscesses occur. In this study, the case history of a patient with central nervous system manifestation of hereditary hemorrhagic telangiectasia showing familiar aggregation of brain abscess will be presented. A young male patient was admitted to Neurological Department because of his first epileptic seizure and progressive right hemispheric symptoms. His examinations showed frontal abscess, which was surgically removed. The frequent nose-bleeding of the patient and recurrent brain abscess in his brother's history provided the possibility of hereditary hemorrhagic telangiectasia. The background of brain abscess were multiple pulmonary arteriovenous malformation, which were embolized by repeated angiography. Familiar brain abscess is very rare. However, in the case of brain abscess especially with familiarity diagnosis of the Rendu-Osler-Weber disease should be considered. PMID:11760648

  18. Acquired Hemophilia A: A Frequently Overlooked Autoimmune Hemorrhagic Disorder

    PubMed Central

    Takeda, Tomohiro

    2014-01-01

    Acquired hemophilia A (AHA) is a rare hemorrhagic disease in which autoantibodies against coagulation factor VIII- (FVIII-) neutralizing antibodies (inhibitors) impair the intrinsic coagulation system. As the inhibitors developed in AHA are autoantibodies, the disease may have an autoimmune cause and is often associated with autoimmune disease. Although acute hemorrhage associated with AHA may be fatal and is costly to treat, AHA is often unrecognized or misdiagnosed. AHA should thus be considered in the differential diagnosis particularly in postpartum women and the elderly with bleeding tendency or prolonged activated partial thromboplastin time. Cross-mixing tests and measurement of FVIII-binding antibodies are useful to confirm AHA diagnosis. For treatment of acute hemorrhage, hemostatic therapy with bypassing agents should be provided. Unlike in congenital hemophilia A with inhibitors, in which immune tolerance induction therapy using repetitive infusions of high-dose FVIII concentrates is effective for inhibitor eradication, immune tolerance induction therapy has shown poor efficacy in treating AHA. Immunosuppressive treatment should thus be initiated to eradicate inhibitors as soon as the diagnosis of AHA is confirmed. PMID:24741588

  19. Transmission of epidemic dengue hemorrhagic fever in easternmost Indonesia.

    PubMed

    Sukri, Nono C; Laras, Kanti; Wandra, Toni; Didi, Sukman; Larasati, Ria P; Rachdyatmaka, Josef R; Osok, Stevie; Tjia, Petrus; Saragih, John M; Hartati, Sri; Listyaningsih, Erlin; Porter, Kevin R; Beckett, Charmagne G; Prawira, Ingerani S; Punjabi, Narain; Suparmanto, Sri A; Beecham, H James; Bangs, Michael J; Corwin, Andrew L

    2003-05-01

    In April 2001, a second suspected outbreak of dengue hemorrhagic fever in the easternmost region of Indonesia was investigated in Merauke, a town located in the southeastern corner of Papua, by the Indonesian Ministry of Health and the U.S. Naval Medical Research Unit No. 2. Principal case criteria of hemorrhagic disease provided for a study enrollment of 15 clinically acute and 37 convalescing subjects. Additionally, 32 comparable age/sex controls were selected from neighboring households. Laboratory diagnosis involved three testing methodologies: virus isolation by cell culture, a reverse transcriptase-polymerase chain reaction (RT-PCR) assay, and serologic assays. Antibody (IgM) to dengue virus was detected in 27% of the acute clinical cases, 30% of the convalescing cases, and only 3% of the matched controls. Dengue 3 was the only viral serotype detected from acute serum samples by the RT-PCR. The mean +/- SD age of the acute and convalescing cases was 7.8 +/- 5.4 years. Overall hospital records accounted for 172 suspected outbreak cases, all urban residents of Merauke with no recent travel history outside the area. The estimated outbreak-associated case fatality rate among all suspected dengue cases was 1.2%. A seven-year retrospective review of hospital records in Merauke showed negligible disease reporting involving hemorrhagic disease prior to the outbreak. PMID:12812338

  20. A retrospective study of acute pancreatitis in patients with hemorrhagic fever with renal syndrome

    PubMed Central

    2013-01-01

    Background Etiological diagnosis is an important part of the diagnosis and treatment of acute pancreatitis. Hantavirus infection is a rare cause of acute pancreatitis, which is easy to ignore. There is a need to analyze clinical features of acute pancreatitis caused by Hantavirus. Methods This is a retrospective study conducted from May 1, 2006 to May 31, 2012 on patients diagnosed with hemorrhagic fever with renal syndrome at our hospital. We reviewed these patients medical records, laboratory results and radiologic examinations to determine the prevalence and summarize clinical features of acute pancreatitis in patients with hemorrhagic fever with renal syndrome. Results A total of 218 patients were diagnosed with hemorrhagic fever with renal syndrome during the 6-year study period. Only 2.8% (6/218) of the total hemorrhagic fever with renal syndrome patients were diagnosed with acute pancreatitis. The first symptom for all six of the patients with acute pancreatitis was fever. All six patients experienced hemorrhage and thrombocytopenia during the disease course, which was different from general acute pancreatitis. In addition, we presented two misdiagnosed clinical cases. Conclusions Acute pancreatitis is not a frequent complication in patients with hemorrhagic fever with renal syndrome. Clinicians should be alerted to the possibility of hemorrhagic fever with renal syndrome when acute pancreatitis patients with epidemiological data have high fever before abdominal pain. PMID:24345089

  1. Pulmonary hemorrhage resulting from bungee jumping.

    PubMed

    Manos, Daria; Hamer, Okka; Müller, Nestor L

    2007-11-01

    Pulmonary hemorrhage is a relatively common complication of blunt chest trauma. Occasionally, it may result from pulmonary barotrauma after scuba diving or from sports activities not associated with barotrauma such as long breath-hold diving. We report a case of symmetric diffuse upper lobe hemorrhage resulting from a bungee jump in a previously healthy man. Bungee jumping is an increasingly popular sport with relatively few reported injuries. To our knowledge pulmonary hemorrhage in this setting has not yet been described. PMID:18043394

  2. Neurogenic stress cardiomyopathy associated with subarachnoid hemorrhage.

    PubMed

    Pinnamaneni, Sowmya; Dutta, Tanya; Melcer, Joshua; Aronow, Wilbert S

    2015-01-01

    Cardiac manifestations are recognized complications of subarachnoid hemorrhage. Neurogenic stress cardiomyopathy is one complication that is seen in acute subarachnoid hemorrhage. It can present as transient diffuse left ventricular dysfunction or as transient regional wall motion abnormalities. It occurs more frequently with neurologically severe-grade subarachnoid hemorrhage and is associated with increased morbidity and poor clinical outcomes. Managing this subset of patients is challenging. Early identification followed by a multidisciplinary team approach can potentially improve outcomes. PMID:25606704

  3. Functional dissection of adenovirus VAI RNA.

    PubMed Central

    Furtado, M R; Subramanian, S; Bhat, R A; Fowlkes, D M; Safer, B; Thimmappaya, B

    1989-01-01

    During the course of adenovirus infection, the VAI RNA protects the translation apparatus of host cells by preventing the activation of host double-stranded RNA-activated protein kinase, which phosphorylates and thereby inactivates the protein synthesis initiation factor eIF-2. In the absence of VAI RNA, protein synthesis is drastically inhibited at late times in infected cells. The experimentally derived secondary structure of VAI RNA consists of two extended base-paired regions, stems I and III, which are joined by a short base-paired region, stem II, at the center. Stems I and II are joined by a small loop, A, and stem III contains a hairpin loop, B. At the center of the molecule and at the 3' side, stems II and III are connected by a short stem-loop (stem IV and hairpin loop C). A fourth, minor loop, D, exists between stems II and IV. To determine sequences and domains critical for function within this VAI RNA structure, we have constructed adenovirus mutants with linker-scan substitution mutations in defined regions of the molecule. Cells infected with these mutants were analyzed for polypeptide synthesis, virus yield, and eIF-2 alpha kinase activity. Our results showed that disruption of base-paired regions in the distal parts of the longest stems, I and III, did not affect function, whereas mutations causing structural perturbations in the central part of the molecule containing stem II, the proximal part of stem III, and the central short stem-loop led to loss of function. Surprisingly, one substitution mutant, sub742, although dramatically perturbing the integrity of the structure of this central portion, showed a wild-type phenotype, suggesting that an RNA with an alternate secondary structure is functional. On the basis of sensitivity to single-strand-specific RNases, we can derive a novel secondary structure for the mutant RNA in which a portion of the sequences may fold to form a structure that resembles the central part of the wild-type molecule

  4. Satellite Detection of Ebola River Hemorrhagic Fever Epidemics Trigger Events

    NASA Technical Reports Server (NTRS)

    Tucker, Compton J.; Pinzon, Jorge E.

    2006-01-01

    Ebola hemorrhagic fever, named after the Ebola River in Central Africa, first appeared in June 1976, during an outbreak in Nzara and Maridi, Sudan. In September 1976, a separate outbreak was recognized in Yambuku, Democratic Republic of the Congo (DRC). One fatal case was identified in Tandala, DRC, in June 1977, followed by another outbreak in Nzara, Sudan, in July 1979. Ebola hemorrhagic fever outbreaks results in a very high mortality of patients who contract the disease: from 50 to 80% of infected people perish from this highly virulent disease. Death is gruesome, with those afflicted bleeding to death from massive hemorrhaging of organs and capillaries. The disease was not identified again until the end of 1994, when three outbreaks occurred almost simultaneously in Africa. In October, an outbreak was identified in a chimpanzee community studied by primatologists in Tal, Cote d'lvoire, with one human infection. The following month, multiple cases were reported in northeast Gabon in the gold panning camps of Mekouka, Andock, and Minkebe. Later that same month, the putative index case of the 1995 Kikwit, DRC, outbreak was exposed through an unknown mechanism while working in a charcoal pit. In Gabon, two additional outbreaks were reported in February and JuIy,1996, respectively, in Mayibout II, a village 40 km south of the original outbreak in the gold panning camps, and a logging camp between Ovan and Koumameyong, near Booue. The largest Ebola hemorrhagic fever epidemic occurred in Gulu District, Uganda from August 2000 to January 2001. In December 2001, Ebola reappeared in the Ogooue-lvindo Province, Gabon with extension into Mbomo District, The Republic of the Congo lasting until July 2002. Since 2002 there have been several outbreaks of Ebola hemorrhagic fever in Gabon and adjacent areas of Congo. Of interest is the seasonal context and occasional temporal clustering of Ebola hemorrhagic fever outbreaks. Near simultaneous appearances of Ebola epidemics in

  5. Hemorrhagic lumbar synovial cyst: case report and literature review

    PubMed Central

    Cannarsa, Gregory; Clark, Shannon W.; Chalouhi, Norah; Zanaty, Mario; Heller, Joshua

    2015-01-01

    ABSTRACT Intraspinal synovial cysts are infrequent causes of back and radicular leg pain. Commonly associated with degenerative spinal disease, the majority of synovial cysts appear in the lumbar spine. Rarely, intracystic hemorrhage can occur through an unclear mechanism. Similarly rare, cysts may also become migratory. The pathogenesis of hemorrhagic synovial cysts remains uncertain and their potential for migration also remains unclear. A 36 year-old male presented to the clinic with 5 months of back pain and leg pain that began after a work-related injury. An initial MRI obtained by another surgeon 3 month prior demonstrated an epidural cystic mass with T1 hypointensity and T2 hyperintensity at L2-L3. With worsening pain, the patient came to our clinic for a second opinion. A second MRI demonstrated resolution of the L2-L3 epidural cystic mass and formation of a new epidural cystic mass at L3-L4 causing compression of the thecal sac. The patient subsequently underwent decompressive hemilaminectomy with cyst removal. We present a case of two lumbar synovial cysts, separated over time and a vertebral level and giving the appearance of a single, migratory cyst. This is the first case of an "occult migratory" synovial cyst with repeat MR imaging capturing spontaneous resolution of the initial cyst and formation of a hemorrhagic cyst one level below. We also present a summary of the 44 cases of hemorrhagic synovial cysts reported in the literature and propose a mechanism that may account for the hemorrhagic and migratory progression in some patients. PMID:26412895

  6. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Hepatitis and Canine Adenovirus... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  7. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Hepatitis and Canine Adenovirus...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  8. 9 CFR 113.305 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Canine Hepatitis and Canine Adenovirus... STANDARD REQUIREMENTS Live Virus Vaccines § 113.305 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine. Canine Hepatitis Vaccine and Canine Adenovirus Type 2 Vaccine shall be prepared from virus-bearing...

  9. 9 CFR 113.202 - Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Canine Hepatitis and Canine Adenovirus...; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Killed Virus Vaccines § 113.202 Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed Virus. Canine Hepatitis and Canine Adenovirus Type 2 Vaccine, Killed...

  10. ANTIGEN DETECTION WITH MONOCLONAL ANTIBODIES FOR THE DIAGNOSIS OF ADENOVIRUS GASTROENTERITIS

    EPA Science Inventory

    The authors have developed a monoclonal antibody-based enzyme immunoassay (EIA) for direct detection of enteric adenoviruses in stool specimens from patients with gastroenteritis. Tests specific for each of the enteric adenoviruses, adenovirus type 40 (Ad40) and type 41 (Ad41) we...

  11. Spontaneous Massive Adrenal Hemorrhage: A Management Dilemma

    PubMed Central

    Agarwal, Anshuman

    2015-01-01

    Abstract Adrenal hemorrhage (AH) is a rare but life-threatening condition. Small focal hemorrhage may present subclinically, but massive hemorrhage may lead to rapid cardiovascular collapse and ultimately death if not diagnosed appropriately and treated quickly. Most cases reported in the literature have been treated conservatively. In an event of increasing hemorrhage during conservative management, it may be tricky to intervene surgically because of the hematoma around the gland. Here we describe a case where we managed a large spontaneous AH by a combination of angioembolization and laparoscopic adrenalectomy. PMID:27579389

  12. Hemorrhagic cystitis: A challenge to the urologist

    PubMed Central

    Manikandan, R.; Kumar, Santosh; Dorairajan, Lalgudi N.

    2010-01-01

    Severe hemorrhagic cystitis often arises from anticancer chemotherapy or radiotherapy for pelvic malignancies. Infectious etiologies are less common causes except in immunocompromised hosts. These cases can be challenging problems for the urologist and a source of substantial morbidity and sometimes mortality for the patients. A variety of modalities of treatment have been described for the management of hemorrhagic cystitis but there is none that is uniformly effective. Some progress has been made in the understanding and management of viral hemorrhagic cystitis. This article reviews the common causes of severe hemorrhagic cystitis and the currently available management options. PMID:20877590

  13. Physical organization of subgroup B human adenovirus genomes.

    PubMed Central

    Tibbetts, C

    1977-01-01

    Cleavage sites of nine bacterial restriction endonucleases were mapped in the DNA of adenovirus type 3 (Ad3) and Ad7, representative serotypes of the "weakly oncogenic" subgroup B human adenoviruses. Of 94 sites mapped, 82 were common to both serotypes, in accord with the high overall sequence homology of DNA among members of the same subgroups. Of the sites in Ad3 and Ad7 DNA, fewer than 20% corresponded to mapped restriction sites in the DNA of Ad2 or Ad5. The latter serotypes represent the "nononcogenic" subgroup C, having only 10 to 20% overall sequence homology with the DNA of subgroup B adenoviruses. Hybridization mapping of viral mRNA from Ad7-infected cells resulted in a complex physical map that was nearly identical to the map of early and late gene clusters in Ad2 DNA. Thus the DNA sequences of human adenoviruses of subgroups B and C have significantly diverged in the course of viral evolution, but the complex organization of the adenovirus genome has been rigidly conserved. Images PMID:916027

  14. [Adenovirus-delivered BMI-1 shRNA].

    PubMed

    Chen, Zhen-Ping; Chen, Xiao-Li; Zhen, Jie

    2009-10-01

    Recently, some plasmid vectors that direct transcription of small hairpin RNAs have been developed, which are processed into functional siRNAs by cellular enzymes. Although these vectors possess certain advantages over synthesized siRNA, many disadvantages exist, including low and variable transfection efficiency. This study was aimed to establish an adenoviral siRNA delivery system without above-mentioned disadvantages on the basis of commercially available vectors. A vector was designed to target the human polycomb gene BMI-1. The pAd-BMI-1shRNA-CMV-GFP vector was produced by cloning a 300 bp U6-BMI-1 cassette from the pGE1BMI-1shRNA plasmid and a CMV-GFP cassette from pAdTrack CMV in pShutter vector. The adenovirus was produced from the 293A packaging cell line and then infected K562 cells. The mRNA and protein levels of Bmi-1 were detected by real time-PCR and Western blot respectively. The results showed that the adenovirus carrying the BMI-1shRNA was successfully produced. After being transfected with the adenovirus, the K562 cells dramatically down-regulated BMI-1 expression, whereas the adenoviruses carrying control shRNA had no effect on BMI-1 expression. It is concluded that the adenoviruses are efficient vectors for delivery of siRNA into mammalian cells and may become a candidate vector carrying siRNA drugs for gene therapy. PMID:19840467

  15. Incorporation of 4-1BB ligand into an adenovirus vaccine vector increases the number of functional antigen-specific CD8 T cells and enhances the duration of protection against influenza-induced respiratory disease.

    PubMed

    Moraes, Theo J; Lin, Gloria H Y; Wen, Tao; Watts, Tania H

    2011-08-26

    T cell based influenza vaccines offer the potential for cross protective immunity to multiple clades of influenza virus. Here we explored the effect of increasing CD8 T cell responses during intranasal vaccination by incorporating a T cell costimulator, 4-1BBL. Inclusion of 4-1BBL in an influenza nucleoprotein (NP)-containing adenoviral vector increased the number of NP-specific CD8 T cells and lowered the vaccine dose required for short-term protection from influenza-induced disease in mice. At higher vaccine doses, the inclusion of 4-1BBL increased the duration of protection of mice from influenza-induced mortality. Bone marrow chimera experiments revealed that the major effects of 4-1BBL were directly on αβ T cells with minor additional effects through cells other than αβ T cells. The implications of these findings are that including 4-1BBL or adjuvants that induce 4-1BBL expression may be of benefit in a vaccine setting for enhancing the magnitude and duration of T cell responses to influenza virus. PMID:21704101

  16. Enhanced expression of adenovirus transforming proteins.

    PubMed Central

    Gaynor, R B; Tsukamoto, A; Montell, C; Berk, A J

    1982-01-01

    Proteins encoded in regions EIA and EIB of human adenoviruses cause transformation of rodent cells. One protein from EIA also stimulates transcription of other early regions at early times in a productive infection. In the past, direct analysis of these proteins synthesized in vivo has been difficult because of the low levels produced in both transformed cells and productively infected cells. We present a simple method which leads to expression of EIA and EIB mRNAs and proteins at 30-fold greater levels than those observed during the early phase of a standard productive infection. Under these conditions, these proteins are among the most prominent translation products of infected cells. This allowed direct visualization of EIA and EIB proteins on two-dimensional gels of pulse-labeled total cell protein. Experiments with EIA and EIB mutants confirm that the identified proteins are indeed encoded in these regions. Two EIA proteins are observed, one translated from each of the major early EIA mRNAs. Both of these EIA proteins are phosphorylated. Images PMID:7143568

  17. Adenovirus hexon modifications influence in vitro properties of pseudotyped human adenovirus type 5 vectors.

    PubMed

    Solanki, Manish; Zhang, Wenli; Jing, Liu; Ehrhardt, Anja

    2016-01-01

    Commonly used human adenovirus (HAdV)-5-based vectors are restricted by their tropism and pre-existing immunity. Here, we characterized novel HAdV-5 vectors pseudotyped with hypervariable regions (HVRs) and surface domains (SDs) of other HAdV types. Hexon-modified HAdV-5 vectors (HV-HVR5, HV-HVR12, HV-SD12 and HV-SD4) could be reconstituted and amplified in human embryonic kidney cells. After infection of various cell lines, we measured transgene expression levels by performing luciferase reporter assays or coagulation factor IX (FIX) ELISA. Dose-dependent studies revealed that luciferase expression levels were comparable for HV-HVR5, HV-SD12 and HV-SD4, whereas HV-HVR12 expression levels were significantly lower. Vector genome copy numbers (VCNs) from genomic DNA and nuclear extracts were then determined by quantitative real-time PCR. Surprisingly, determination of cell- and nuclear fraction-associated VCNs revealed increased VCNs for HV-HVR12 compared with HV-SD12 and HV-HVR5. Increased nuclear fraction-associated HV-HVR12 DNA molecules and decreased transgene expression levels were independent of the cell line used, and we observed the same effect for a hexon-modified high-capacity adenoviral vector encoding canine FIX. In conclusion, studying hexon-modified adenoviruses in vitro demonstrated that HVRs but also flanking hexon regions influence uptake and transgene expression of adenoviral vectors. PMID:26519158

  18. Emerging infectious diseases: Focus on infection control issues for novel coronaviruses (Severe Acute Respiratory Syndrome-CoV and Middle East Respiratory Syndrome-CoV), hemorrhagic fever viruses (Lassa and Ebola), and highly pathogenic avian influenza viruses, A(H5N1) and A(H7N9).

    PubMed

    Weber, David J; Rutala, William A; Fischer, William A; Kanamori, Hajime; Sickbert-Bennett, Emily E

    2016-05-01

    Over the past several decades, we have witnessed the emergence of many new infectious agents, some of which are major public threats. New and emerging infectious diseases which are both transmissible from patient-to-patient and virulent with a high mortality include novel coronaviruses (SARS-CoV, MERS-CV), hemorrhagic fever viruses (Lassa, Ebola), and highly pathogenic avian influenza A viruses, A(H5N1) and A(H7N9). All healthcare facilities need to have policies and plans in place for early identification of patients with a highly communicable diseases which are highly virulent, ability to immediately isolate such patients, and provide proper management (e.g., training and availability of personal protective equipment) to prevent transmission to healthcare personnel, other patients and visitors to the healthcare facility. PMID:27131142

  19. The adenovirus e3 promoter is sensitive to activation signals in human T cells.

    PubMed

    Mahr, Jeffrey A; Boss, Jeremy M; Gooding, Linda R

    2003-01-01

    The group C adenoviruses typically cause acute respiratory disease in young children. In addition, a persistent phase of infection has been observed in which virus may be shed for years without producing overt pathology. Our laboratory recently reported that group C adenovirus DNA can be found in tonsil and adenoid T lymphocytes from the majority of pediatric donors (C. T. Garnett, D. Erdman, W. Xu, and L. R. Gooding, J. Virol. 76:10608-10616, 2002). This finding suggests that immune evasion strategies of human adenoviruses may be directed, in part, toward protection of persistently or latently infected T lymphocytes. Many of the adenoviral gene products implicated in prevention of immune destruction of virus-infected cells are encoded within the E3 transcription unit. In this study, the E3 promoter was evaluated for sensitivity to T-cell activation signals by using a promoter reporter plasmid. Indeed, this promoter is extremely sensitive to T-cell activation, with phorbol myristate acetate (PMA) plus ionomycin increasing E3-directed transcription 100-fold. By comparison, in the same cells E1A expression leads to a 5.5-fold increase in transcription from the E3 promoter. In contrast to induction by E1A, activation by PMA plus ionomycin requires the two E3 NF-kappaB binding sites. Interestingly, expression of E1A inhibits induction of the E3 promoter in response to T-cell activation while increasing E3 promoter activity in unactivated cells. Collectively, these data suggest that the E3 promoter may have evolved the capacity to respond to T-cell activation in the absence of E1A expression and may act to upregulate antiapoptotic gene expression in order to promote survival of persistently infected T lymphocytes. PMID:12502827

  20. A Case Report of Acute Acalculous Cholecystitis and Acute Hemorrhagic Cystitis due to Salmonella Typhi

    PubMed Central

    Beyazal Polat, Hatice; Beyazal Çeliker, Fatma

    2014-01-01

    Acute acalculous cholecystitis and acute hemorrhagic cystitis due to Salmonella Typhi are a rare condition. A 24-year-old female patient was admitted to our clinic with abdominal pain, nausea, fever, headache, urinary burning, and bloody urine. Based on clinical, laboratory, and radiological evaluations, the patient was diagnosed with acute acalculous cholecystitis and acute hemorrhagic cystitis due to Salmonella Typhi. The patient was treated with intravenous ceftriaxone for two weeks. After the treatment, the patient's clinical and laboratory findings improved. Acute acalculous cholecystitis due to Salmonella Typhi concomitant with acute hemorrhagic cystitis is very rare and might be difficult to diagnose. Infectious agents such as Salmonella Typhi should be considered when acute acalculous cholecystitis and acute hemorrhagic cystitis are detected in adult patients with no underlying diseases. PMID:25161668

  1. Molecular, Cellular and Clinical Aspects of Intracerebral Hemorrhage: Are the Enemies Within?

    PubMed

    Righy, Cássia; Bozza, Marcelo T; Oliveira, Marcus F; Bozza, Fernando A

    2016-01-01

    Hemorrhagic stroke is a disease with high incidence and mortality rates. In addition to the mass lesions that result from hemorrhagic stroke, substances such as the blood-derived products (BDP) (hemoglobin (Hb), heme and iron) induce a potent inflammatory response and exert direct toxic effects on neurons, astrocytes, and microglia. In the present review, we discuss the mechanisms of brain injury secondary to hemorrhagic stroke, focusing on the involvement of BDP as major players of cellular redox imbalance, inflammation, and glutamate excitotoxicity. Potential natural mechanisms of protection against free Hb and heme such as haptoglobin and hemopexin, respectively, are highlighted. We finally discuss the experimental and clinical trials targeting free iron and heme scavenging as well as inflammation, as potential new therapies to minimize the devastating effects of hemorrhagic stroke on brain structure and function. PMID:26714583

  2. Higher mortality due to intracerebral hemorrhage in dialysis patients: a comparison with the general population in Japan.

    PubMed

    Wakasugi, Minako; Matsuo, Koji; Kazama, Junichiro James; Narita, Ichiei

    2015-02-01

    Cerebrovascular diseases, including intracerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage, remain prevalent causes of morbidity and mortality among dialysis patients. Their mortality rate for cerebrovascular diseases is roughly three times higher than that in the general population. However, whether mortality rates for all subtypes of cerebrovascular diseases are equally higher has not been evaluated. The aim of this study was to determine the mortality rate for each stroke subtype, comparing dialysis patients and the general population in Japan. We used mortality data reported by the Japanese Society for Dialysis Therapy and national Vital Statistics data between 2008 and 2009. We calculated standardized mortality ratios and compared the mortality rates for stroke subtypes including intracerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage. During the 2-year study period, 51 994 and 933 deaths from intracerebral hemorrhage, 79 124 and 511 deaths from cerebral infarction, and 24 957 and 147 deaths from subarachnoid hemorrhage were recorded per 252 million person-years and per 546 474 dialysis patient-years, respectively. Standardized mortality ratios among dialysis patients relative to the general population were 3.8 (95% confidence interval, 3.6-4.1), 1.3 (1.2-1.4), and 1.3 (1.1-1.6) for intracerebral hemorrhage, cerebral infarction, and subarachnoid hemorrhage, respectively. Intracerebral hemorrhage was the highest cause of mortality in the dialysis population, although cerebral infarction was the highest in the general population. Relative to the general population in Japan, Japanese dialysis patients had higher mortality rates, especially for intracerebral hemorrhage. PMID:25196294

  3. Disseminated adenovirus infection in an immunocompromised host. Pitfalls in diagnosis.

    PubMed

    Landry, M L; Fong, C K; Neddermann, K; Solomon, L; Hsiung, G D

    1987-09-01

    In this report, a bone marrow transplant recipient with rapidly fatal gastroenteritis is presented. The presence of intranuclear inclusions on postmortem light microscopic examination of liver, lung, and small bowel tissue was considered diagnostic of cytomegalovirus infection. However, electron microscopic examination of liver tissue demonstrated adenovirus infection. This was confirmed by isolation of an adenovirus type 2 with unusual laboratory features from liver, lung, colon contents, serum, esophageal swab, and oral ulcerations. Results of a complement fixation test for antibodies to adenovirus performed on postmortem serum samples were negative, and a titer of 1:4 was noted for antibody against cytomegalovirus. This case illustrates the diagnostic pitfalls that may be encountered in establishing a specific viral diagnosis in severely ill patients. PMID:2821806

  4. Capsid-like Arrays in Crystals of Chimpanzee Adenovirus Hexon

    SciTech Connect

    Xue,F.; Burnett, R.

    2006-01-01

    The major coat protein, hexon, from a chimpanzee adenovirus (AdC68) is of interest as a target for vaccine vector modification. AdC68 hexon has been crystallized in the orthorhombic space group C222 with unit cell dimensions of a = 90.8 Angstroms, b = 433.0 Angstroms, c = 159.3 Angstroms, and one trimer (3 x 104,942 Da) in the asymmetric unit. The crystals diffract to 2.1 Angstroms resolution. Initial studies reveal that the molecular arrangement is quite unlike that in hexon crystals for human adenovirus. In the AdC68 crystals, hexon trimers are parallel and pack closely in two-dimensional continuous arrays similar to those formed on electron microscope grids. The AdC68 crystals are the first in which adenovirus hexon has molecular interactions that mimic those used in constructing the viral capsid.

  5. Species-Specific Identification of Human Adenoviruses in Sewage.

    PubMed

    Wieczorek, Magdalena; Krzysztoszek, Arleta; Witek, Agnieszka

    2015-01-01

    Human adenovirus (HAdV) diversity in sewage was assessed by species-specific molecular methods. Samples of raw sewage were collected in 14 sewage disposal systems from January to December 2011, in Poland. HAdVs were detected in 92.1% of the analysed sewage samples and was significantly higher at cities of over 100 000 inhabitants. HAdV DNA was detected in sewage during all seasons. The most abundant species identified were HAdV-F (average 89.6%) and -A (average 19.6%), which are associated with intestine infections. Adenoviruses from B species were not detected. The result of the present study demonstrate that human adenoviruses are consistently present in sewage in Poland, demonstrating the importance of an adequate treatment before the disposal in the environment. Multiple HAdV species identified in raw sewage provide new information about HAdV circulation in the Polish population. PMID:26094312

  6. Adenovirus Vectors for Gene Therapy, Vaccination and Cancer Gene Therapy

    PubMed Central

    Wold, William S.M.; Toth, Karoly

    2015-01-01

    Adenovirus vectors are the most commonly employed vector for cancer gene therapy. They are also used for gene therapy and as vaccines to express foreign antigens. Adenovirus vectors can be replication-defective; certain essential viral genes are deleted and replaced by a cassette that expresses a foreign therapeutic gene. Such vectors are used for gene therapy, as vaccines, and for cancer therapy. Replication-competent (oncolytic) vectors are employed for cancer gene therapy. Oncolytic vectors are engineered to replicate preferentially in cancer cells and to destroy cancer cells through the natural process of lytic virus replication. Many clinical trials indicate that replication-defective and replication-competent adenovirus vectors are safe and have therapeutic activity. PMID:24279313

  7. Characterization of a novel adenovirus isolated from a skunk.

    PubMed

    Kozak, Robert A; Ackford, James G; Slaine, Patrick; Li, Aimin; Carman, Susy; Campbell, Doug; Welch, M Katherine; Kropinski, Andrew M; Nagy, Éva

    2015-11-01

    Adenoviruses are a ubiquitous group of viruses that have been found in a wide range of hosts. A novel adenovirus from a skunk suffering from acute hepatitis was isolated and its DNA genome sequenced. The analysis revealed this virus to be a new member of the genus Mastadenovirus, with a genome of 31,848 bp in length containing 30 genes predicted to encode proteins, and with a G+C content of 49.0%. Global genomic organization indicated SkAdV-1 was similar in organization to bat and canine adenoviruses, and phylogenetic comparison suggested these viruses shared a common ancestor. SkAdV-1 demonstrated an ability to replicate in several mammalian liver cell lines suggesting a potential tropism for this virus. PMID:26189043

  8. Crystal Structure of Enteric Adenovirus Serotype 41 Short Fiber Head

    PubMed Central

    Seiradake, Elena; Cusack, Stephen

    2005-01-01

    Human enteric adenoviruses of species F contain two fibers in the same virion, a long fiber which binds to coxsackievirus and adenovirus receptor (CAR) and a short fiber of unknown function. We have determined the high-resolution crystal structure of the short fiber head of human adenovirus serotype 41 (Ad41). The short fiber head has the characteristic fold of other known fiber heads but has three unusual features. First, it has much shorter loops between the beta-strands. Second, one of the usually well-ordered beta-strands on the distal face of the fiber head is highly disordered and this same region is sensitive to digestion with pepsin, an enzyme occurring naturally in the intestinal tract, the physiological environment of Ad41. Third, the AB loop has a deletion giving it a distinct conformation incompatible with CAR binding. PMID:16254343

  9. Dengue virus–induced hemorrhage in a nonhuman primate model

    PubMed Central

    Onlamoon, Nattawat; Noisakran, Sansanee; Hsiao, Hui-Mien; Duncan, Alexander; Villinger, Francois; Ansari, Aftab A.

    2010-01-01

    Lack of a dengue hemorrhagic animal model recapitulating human dengue virus infection has been a significant impediment in advancing our understanding of the early events involved in the pathogenesis of dengue disease. In efforts to address this issue, a group of rhesus macaques were intravenously infected with dengue virus serotype 2 (strain 16 681) at 1 × 107 PFU/animal. A classic dengue hemorrhage developed 3 to 5 days after infection in 6 of 6 animals. Blood chemistry appeared to be normal with exception of creatine phosphokinase, which peaked at 7 days after infection. A modest thrombocytopenia and noticeable neutropenia concomitant with slight decrease of hemoglobin and hematocrit were registered. In addition, the concentration of D-dimer was elevated significantly. Viremia peaked at 3 to 5 days after infection followed by an inverse relationship between T and B lymphocytes and a bimodal pattern for platelet-monocytes and platelet-neutrophil aggregates. Dengue virus containing platelets engulfed by monocytes was noted at 8 or 9 days after infection. Thus, rhesus macaques inoculated intravenously with a high dose of dengue virus produced dengue hemorrhage, which may provide a unique platform to define the early events in dengue virus infection and help identify which blood components contribute to the pathogenesis of dengue disease. PMID:20042723

  10. Thrombo-hemorrhagic deaths in acute promyelocytic leukemia.

    PubMed

    Breccia, Massimo; Lo Coco, Francesco

    2014-05-01

    Acute promyelocytic leukemia (APL) has become the most curable form of acute myeloid leukemia after the advent of all-trans retinoic acid (ATRA). However, early deaths (ED) mostly due to the disease-associated coagulopathy remain the major cause of treatment failure. In particular, hemorrhagic events account for 40-65% of ED and several prognostic factors have been identified for such hemorrhagic deaths, including poor performance status, high white blood cell (WBC) count and coagulopathy. Occurrence of thrombosis during treatment with ATRA may be associated with differentiation syndrome (DS) or represent an isolated event. Some prognostic factors have been reported to be associated with thrombosis, including increased WBC or aberrant immunophenotype of leukemic promyelocytes. Aim of this review is to report the incidence, severity, possible pathogenesis and clinical manifestations of thrombo-haemorrhagic deaths in APL. PMID:24862130

  11. Acute gingival bleeding as a complication of dengue hemorrhagic fever.

    PubMed

    Khan, Saif; Gupta, N D; Maheshwari, Sandhya

    2013-07-01

    Dengue fever is mosquito borne disease caused by dengue virus (DENV) of Flaviviridae family. The clinical manifestations range from fever to severe hemorrhage, shock and death. Here, we report a case of 20-year-old male patient undergoing orthodontic treatment presenting with acute gingival bleeding with a history of fever, weakness, backache, retro orbital pain and ecchymosis over his right arm. The hematological investigations revealed anemia, thrombocytopenia and positive dengue non-structural protein-1 antigen and also positive immunoglobulin M and immunoglobulin G antibodies for DENV. Patient was diagnosed as a case of dengue hemorrhagic fever and was immediately referred for appropriate management. This case report emphasizes the importance of taking correct and thorough medical history. PMID:24174736

  12. Recent advances in research on Crimean-Congo hemorrhagic fever

    PubMed Central

    Papa, Anna; Mirazimi, Ali; Köksal, Iftihar; Estrada-Pena, Augustin; Feldmann, Heinz

    2014-01-01

    Crimean-Congo hemorrhagic fever (CCHF) is an expanding tick-borne hemorrhagic disease with increasing human and animal health impact. Immense knowledge was gained over the past 10 years mainly due to advances in molecular biology, but also driven by an increased global interest in CCHFV as an emerging/re-emerging zoonotic pathogen. In the present article we discuss the advances in research with focus on CCHF ecology, epidemiology, pathogenesis, diagnostics, prophylaxis and treatment. Despite tremendous achievements, future activities have to concentrate on the development of vaccines and antivirals/therapeutics to combat CCHF. Vector studies need to continue for better public and animal health preparedness and response. We conclude with a roadmap for future research priorities. PMID:25453328

  13. Hyperdense renal masses: a CT manifestation of hemorrhagic renal cysts

    SciTech Connect

    Sussman, S.; Cochran, S.T.; Pagani, J.J.; McArdle, C.; Wong, W.; Austin, R.; Curry, N.; Kelly, K.M.

    1984-01-01

    Eleven patients with sharply circumscribed round to ovoid renal cysts measuring 70-90 H on CT are reported. The cysts were hyperdense on unenhanced scans, measuring 30-60 H greater than the adjacent parenchyma, and either hypodense, isodense, or hyperdense on enhanced scans. Four patients had polycystic kidney disease; of the other 7 patients, the cysts were cortical in 6 and parapelvic in 1. Eight patients had a solitary cyst and 3 had multiple cysts. Sonography demonstrated internal echoes and/or lack of increased through-transmission in 6 patients. Pathological analysis was available in 6 cases and indicated a benign, hemorrhagic renal cyst. This hyperdense CT appearance is characteristic of some hemorrhagic renal cysts, though differentiation between benign and malignant cysts requires cyst puncture and/or surgery.

  14. [HORMONAL-GENETIC SCREENING IN PATIENTS, SUFFERING GASTRODUODENAL ULCER HEMORRHAGE].

    PubMed

    Duzhiy, I D; Romanyuk, A M; Lyndin, M C; Bratushka, V V; Dubnytskiy, V Yu; Shevchenko, Yu Yu; Kharchenko, S V

    2015-11-01

    Genetic-hormonal regulation plays a key pathophysiologic role in a blood loss on background of complicated gastroduodenal ulcer disease, but a clinical significance of some genes of compensatory steroidogenesis remains unrevealed. Examination of 63 patients, using a chain reaction with polymerase (CRP); analysis of length of restriction fragments (CRP-RFLP) and immunohistochemical investigation of gastroduodenal mucosa were performed on the base of a Sumsky Rural Clinical Hospital. Trustworthy difference of distribution of polymorphic genes ESR1 and VKORC1 in patients of both gender in presence of the ulcer hemorrhage was not revealed, excluding genotype A/A VKORC1, what trustworthy more frequently was revealed in women (p < 0.05). There was established, that intact zone of gastric fundus owes immunoreactivity towards alpha-receptors of estrogen in nuclei of epitheliocytes and stromocytes. Diagnosis of polymorphic gene VKORC1 and expression of the estrogen receptors may serve the base for pathogenetic therapy in patients with hemorrhage occurrence. PMID:26939421

  15. The Prevalence of Rotavirus and Adenovirus in the Childhood Gastroenteritis

    PubMed Central

    Ozsari, Tamer; Bora, Gulhan; Kaya, Bulent; Yakut, Kahraman

    2016-01-01

    Background Acute gastroenteritis stemming from viral causes is very common during the childhood period. Rotavirus and enteric adenovirus are the most common factors of acute gastroenteritis encountered in infants and children. However, the epidemiology of rotavirus and enteric adenovirus gastroenteritis in the east Anatolia region is not well-known. Objectives We aimed to evaluate the relationship between the distribution of antigen positivity in rotavirus and enteric adenovirus antigen tests required cases and demographic data retrospectively in pediatric patients admitted to our hospital. Patients and Methods The records of stool sample analyses for 1154 patients admitted to our hospital from June 2011 to December 2011 with complaints of diarrhea were retrospectively examined. The presence of rotavirus and enteric adenovirus antigens in stool specimens was investigated by means of an immunochromatographic test. Results Viral antigens were detected in 327 (28.3%) stool specimens out of 1154. Among the positive results, the frequency was 73.7% for rotavirus and 26.2% for adenovirus. While the detected rotavirus antigen rate was high for all age groups, it was highest for children under the age of 2, with a rate of 57.1%. Moreover, the rotavirus infections were observed at a rate of 44.3% in winter and of 24.6% in autumn. Conclusions The most important factor in childhood acute gastroenteritis in east Anatolia is the rotavirus. Rotavirus and adenovirus antigens should be routinely investigated as a factor in fresh stool samples for the accurate diagnosis and treatment of gastroenteritis in children in the winter and autumn months.

  16. Transient ST elevation and left ventricular asynergy associated with normal coronary artery and Tc-99m PYP Myocardial Infarct Scan in subarachnoid hemorrhage.

    PubMed

    Chang, P C; Lee, S H; Hung, H F; Kaun, P; Cheng, J J

    1998-01-31

    A 72-year-old woman who presented with transient electrocardiographic ST segment elevation and left ventricular asynergy in an acute phase of subarachnoid hemorrhage was found to have normal coronary angiogram and normal Tc-99m PYP myocardial infarct scan. These findings suggested that noninvasive Tc-99m PYP myocardial infarct scan could substitute coronary angiogram for differentiating wall motion and electrocardiographic abnormalities secondary to subarachnoid hemorrhage from those caused by coronary artery disease in patients with subarachnoid hemorrhage. PMID:9510495

  17. Spontaneous Retroperitoneal Hemorrhage from Adrenal Artery Aneurysm

    SciTech Connect

    Gonzalez Valverde, F.M. Balsalobre, M.; Torregrosa, N.; Molto, M.; Gomez Ramos, M.J.; Vazquez Rojas, J.L.

    2007-04-15

    Spontaneous adrenal hemorrhage is a very rare but serious disorder of the adrenal gland that can require emergent treatment. We report on a 42-year-old man who underwent selective angiography for diagnosis and treatment of retroperitoneal hemorrhage from small adrenal artery aneurysm. This case gives further details about the value of transluminal artery embolization in the management of visceral aneurysm rupture.

  18. Spontaneous bilateral adrenal hemorrhage following cholecystectomy

    PubMed Central

    Dahan, Meryl; Lim, Chetana; Salloum, Chady

    2016-01-01

    Postoperative bilateral adrenal hemorrhage is a rare but potentially life-threatening complication. This diagnosis is often missed because the symptoms and laboratory results are usually nonspecific. We report a case of bilateral adrenal hemorrhage associated with acute primary adrenal insufficiency following laparoscopic cholecystectomy. The knowledge of this uncommon complication following any abdominal surgery allows timey diagnosis and rapid treatment. PMID:27275469

  19. Bullous hemorrhagic dermatosis induced by enoxaparin.

    PubMed

    Gouveia, Ana Isabel; Lopes, Leonor; Soares-Almeida, Luis; Filipe, Paulo

    2016-06-01

    The bullous hemorrhagic dermatosis induced by enoxaparin is a rare adverse reaction, which may be under-reported given its favorable evolution. We report a 71-year-old man who developed hemorrhagic bullae at sites distant from subcutaneous enoxaparin injections. It is important that clinicians be aware of the different adverse reactions of these widely used drugs. PMID:25942690

  20. [Hemorrhagic complications during warfarin treatment].

    PubMed

    Gumulec, J; Kessler, P; Penka, M; Klodová, D; Králová, S; Brejcha, M; Wróbel, M; Sumná, E; Blatný, J; Klaricová, K; Riedlová, P; Lasota, Z

    2006-03-01

    Bleeding is probably the major complication of anticoagulant treatment with vitamin K antagonists represented nowadays mostly by warfarin in the Czech Republic. The main risk factors in hemorrhagic complications of warfarinisation are the intensity and instability of the anticoagulant treatment, individual patient characteristics, warfarin interactions with other drugs and the length of the anticoagulant therapy. Severe bleeding in warfarin patients is most effectively brought about by a fast and complete undoing of the anticoagulation effect of the drug employing the prothrombin complex concentrate and slow i.v. vitamin K1 infusion regardless of the reason for the anticoagulation. This approach can secure the minimalisation of the bleeding's negative consequences. A less severe bleeding or asymptomatic increase in the international normalized ratio can be treated effectively by skipping or decreasing of the warfarin dosage and/or oral administration of vitamin K1 (i.v. administration only in selected higher risk cases) that does result only in a partial consolidation of coagulopathy but of such type that the risk of thrombotic event requires. The article's goal is to contribute to the treatment standardization in patients with warfarin overdose and/or with hemorrhagic complications due to warfarin treatment and it is available at www.thrombosis.cz. The guidelines include a ready-reference chart whose objective is immediate and quick crash course in the clinical practice. PMID:16637455

  1. [Treatment alternatives in massive hemorrhage].

    PubMed

    Fernández-Hinojosa, E; Murillo-Cabezas, F; Puppo-Moreno, A; Leal-Noval, S R

    2012-10-01

    Massive hemorrhage is the main cause of mortality and morbidity in trauma patients, and is one of the most important causes in any patient following major surgery. Conventional treatment consists of volume replacement, including the transfusion of blood products, so that tissue perfusion and oxygenation may be maintained. Associated hypothermia, acidosis and coagulopathy is a lethal triad. This review focuses on the latest therapeutic management of massive hemorrhage. The authors advocate the use of crystalloids as per protocol (controlled volumes) in order to achieve a systolic blood pressure of 85mmHg. The administration of the three blood products (red cells, plasma, and platelets) should be on a 1:1:1 basis. Where possible, this in turn should be guided by thromboelastography performed at point of care near the patient. Coagulopathy can occur early and late. With the exception of tranexamic acid, the cost-benefit relationships of the hemostatic agents, such as fibrinogen, prothrombin complex, and recombinant F VII, are subject to discussion. PMID:22321860

  2. Subchorionic hemorrhage treatment with dydrogesterone.

    PubMed

    Pelinescu-Onciul, Dimitrie

    2007-10-01

    The objective of the study was to evaluate the efficacy of progestogenic therapy for the prevention of spontaneous abortions in patients with subchorionic hemorrhage. One hundred pregnant women with bleeding and ultrasonographic evidence of subchorionic hematoma were treated with oral dydrogesterone 40 mg/day. Only cases in which the embryo was viable were included. The follow-up included ultrasonography and intravaginal examination. Of the 100 pregnancies, 93 had a favorable evolution with maintenance of pregnancy. The abortion rate was therefore 7%. This compares with an abortion rate of 18.7% obtained in a previous study in women with subchorionic hematoma treated with micronized progesterone. The abortion rate was therefore reduced by up to 37% with dydrogesterone, as most cases had large-volume hematomas at the first visit and thus a poor prognosis. In conclusion, the marked immunomodulatory effect of dydrogesterone in maintaining a T helper-2 cytokine balance means that it is a good choice for preventing abortion in women suffering from subchorionic hemorrhage. PMID:17943544

  3. History of Preclinical Models of Intracerebral Hemorrhage

    PubMed Central

    Ma, Qingyi; Khatibi, Nikan; Chen, Hank; Zhang, John H.

    2013-01-01

    In order to understand a disease process, effective modeling is required that can assist scientists in understanding the pathophysiological processes that take place. Intracerebral hemorrhage (ICH), a devastating disease representing 15% of all stroke cases, is just one example of how scientists have developed models that can effectively mimic human clinical scenarios. Currently there are three models of hematoma injections that are being used to induce an ICH in subjects. They include the microballoon model introduced in 1987 by Dr. David Mendelow, the bacterial collagenase injection model introduced in 1990 by Dr. Gary Rosenberg, and the autologous blood injection model introduced by Dr. Guo-Yuan Yang in 1994. These models have been applied on various animal models beginning in 1963 with canines, followed by rats and rabbits in 1982, pigs in 1996, and mice just recently in 2003. In this review, we will explore in detail the various injection models and animal subjects that have been used to study the ICH process while comparing and analyzing the benefits and disadvantages of each. PMID:21725723

  4. Hemorrhagic fever with renal syndrome in Montenegro.

    PubMed

    Gledovic, Z B; Jeknic, A S; Grgurevic, A D; Rakocevic, B B; Bozovic, B R; Mugosa, B V

    2008-09-01

    The objective of the study was to analyze the epidemiological features of hemorrhagic fever with renal syndrome (HFRS) in Montenegro. The study included 169 cases of HFRS diagnosed in the period between 1995 and 2005 according to the clinical symptoms and serological confirmation. For the analysis of the demographic characteristics of the cases, as well as of the chronological and topographical features of the disease, a descriptive epidemiological method was employed. The average incidence rate in the observed period was 2.6 per 100,000. In the observed period, 8 people died; the average case fatality rate was 4.8% (range: 0.1-15%). Among the diseased persons, 116 were males and 53 were females; most of the cases were adults. The greatest number of HFRS cases occurred during the summer months. The highest incidence rates were registered in the northeastern, rural part of the country. The most frequent type of hantaviruses in Montenegro were Dobrava-Belgrade and Hantaan, carried by rodent species, i.e., the yellow-neck mouse and the striped-field mouse. It is likely that HFRS in Montenegro will become more common in the near future, unless public health control measures are taken. PMID:18806348

  5. History of preclinical models of intracerebral hemorrhage.

    PubMed

    Ma, Qingyi; Khatibi, Nikan H; Chen, Hank; Tang, Jiping; Zhang, John H

    2011-01-01

    In order to understand a disease process, effective modeling is required that can assist scientists in understanding the pathophysiological processes that take place. Intracerebral hemorrhage (ICH), a devastating disease representing 15% of all stroke cases, is just one example of how scientists have developed models that can effectively mimic human clinical scenarios. Currently there are three models of hematoma injections that are being used to induce an ICH in subjects. They include the microballoon model introduced in 1987 by Dr. David Mendelow, the bacterial collagenase injection model introduced in 1990 by Dr. Gary Rosenberg, and the autologous blood injection model introduced by Dr. Guo-Yuan Yang in 1994. These models have been applied on various animal models beginning in 1963 with canines, followed by rats and rabbits in 1982, pigs in 1996, and mice just recently in 2003. In this review, we will explore in detail the various injection models and animal subjects that have been used to study the ICH process while comparing and analyzing the benefits and disadvantages of each. PMID:21725723

  6. Crimean-Congo hemorrhagic fever in Iran

    PubMed Central

    Keshtkar-Jahromi, Maryam; Sajadi, Mohammad M.; Ansari, Hossein; Mardani, Masoud; Naieni, Kourosh Holakouie

    2014-01-01

    The presence of Crimean-Congo hemorrhagic fever virus (CCHFV) in Iran was first identified in studies of livestock sera and ticks in the 1970s, but the first human infection was not diagnosed until 1999. Since that time, the number of cases of CCHF in Iran has markedly increased. Through January 2012, articles in the published literature have reported a total of 870 confirmed cases, with 126 deaths, for a case fatality rate (CFR) of 17.6%. The disease has been seen in 26 of the country’s 31 provinces, with the greatest number of cases in Sistan and Baluchestan, Isfahan, Fars, Tehran, Khorasan, and Khuzestan provinces. The increase in CCHF in Iran has paralleled that in neighboring Turkey, though the number of cases in Turkey has been much larger, with an overall CFR of around 5%. In this article, we review the features of CCHF in Iran, including its history, epidemiology, animal and tick reservoirs, current surveillance and control programs, diagnostic methods, clinical features and experience with ribavirin therapy, and consider possible explanations for the difference in the CFR of CCHF between Iran and Turkey. The emergence of CCHF in Iran calls for countermeasures at many levels to protect the population, but also provides opportunities for studying the epidemiology, diagnosis and management of the disease. PMID:23872313

  7. Neural stem cell-mediated delivery of oncolytic adenovirus.

    PubMed

    Kim, Julius W; Kane, J Robert; Young, Jacob S; Chang, Alan L; Kanojia, Deepak; Qian, Shuo; Spencer, Drew A; Ahmed, Atique U; Lesniak, Maciej S

    2015-01-01

    The use of stem cells (SCs) as carriers for therapeutic agents has now progressed to early clinical trials. These clinical trials exploring SC-mediated delivery of oncolytic adenoviruses will commence in the near future, hopefully yielding meritorious results that can provoke further scientific inquiry. Preclinical animal studies have demonstrated that SCs can be successfully loaded with conditionally-replicative adenoviruses and delivered to the tumor, whereupon they may evoke pronounced therapeutic efficacy. In this protocol, we describe the maintenance of SCs, provide an analysis of optimal adenoviral titers for SC loading, and evaluate the optimized viral loading on SCs. PMID:25827347

  8. Human Adenovirus Type 2 but Not Adenovirus Type 12 Is Mutagenic at the Hypoxanthine Phosphoribosyltransferase Locus of Cloned Rat Liver Epithelial Cells

    PubMed Central

    Paraskeva, Christos; Roberts, Carl; Biggs, Paul; Gallimore, Phillip H.

    1983-01-01

    Using resistance to the base analog 8-azaguanine as a genetic marker, we showed that adenovirus type 2, but not adenovirus type 12, is mutagenic at the hypoxanthine phosphoribosyltransferase locus of cloned diploid rat liver epithelial cells. Adenovirus type 2 increased the frequency of 8-azaguanine-resistant colonies by up to ninefold over the spontaneous frequency, depending on expression time and virus dose. PMID:6572280

  9. Prevalence of rotavirus and adenovirus associated with diarrhea among displaced communities in Khartoum, Sudan

    PubMed Central

    2013-01-01

    Background Diarrheal diseases represent a major worldwide public health problem particularly in developing countries. Each year, at least four million children under five years of age die from diarrhea. Rotavirus, enteric adenovirus and some bacterial species are the most common identified infectious agents responsible for diarrhea in young children worldwide. This study was conducted to determine prevalence of rotavirus and adenovirus associated with diarrhea among displaced communities in Khartoum state, Sudan. Methods A total of seven hundred and ten patients, children and adults, suffering from diarrhea were examined. The clinical history, socio-demographic characteristics, physical examination findings and laboratory investigations were recorded. Stool samples or rectal swabs were collected and tested for rotavirus and adenovirus antigens using the immuno-chromatography test (ICT). Characterization of the identified Rotaviruses, as a major cause of diarrhea, was then made using real time-reverse transcription PCR. To make the study legal, an ethical clearance was obtained from Sudan Ministry of health- Research Ethical Committee. Written consent was taken from adult subjects, and also from children mothers. The participants were informed using simple language about the infection, aim of the research and the benefits of the study. Results Out of the 710 patients, viral pathogens were detected in only 99 cases (13.9%). Of the 99 cases of viral diarrhea, 83 (83.8%) were due to rotaviruses while 16 (16.2%) attributed to adenovirus. Of the 83 rotaviruses identified, 42 were characterized by RT-PCR, of these 40 (95.2%) were proved as type A (VP6), and 2 (4.8%) type C (VP7). Type C (VP7) rotavirus was detected in samples collected from children under 5years only. Conclusions In conclusion, most cases of viral diarrhea are found to be caused by rotavirus especially among children less than five years. Most of the identified rotavirus belonged to type A (VP6). It was

  10. Apical localization of the coxsackie-adenovirus receptor by glycosyl-phosphatidylinositol modification is sufficient for adenovirus-mediated gene transfer through the apical surface of human airway epithelia.

    PubMed

    Walters, R W; van't Hof, W; Yi, S M; Schroth, M K; Zabner, J; Crystal, R G; Welsh, M J

    2001-08-01

    In well-differentiated human airway epithelia, the coxsackie B and adenovirus type 2 and 5 receptor (CAR) resides primarily on the basolateral membrane. This location may explain the observation that gene transfer is inefficient when adenovirus vectors are applied to the apical surface. To further test this hypothesis and to investigate requirements and barriers to apical gene transfer to differentiated human airway epithelia, we expressed CAR in which the transmembrane and cytoplasmic tail were replaced by a glycosyl-phosphatidylinositol (GPI) anchor (GPI-CAR). As controls, we expressed wild-type CAR and CAR lacking the cytoplasmic domain (Tailless-CAR). All three constructs enhanced gene transfer with similar efficiencies in fibroblasts. In airway epithelia, GPI-CAR localized specifically to the apical membrane, where it bound adenovirus and enhanced gene transfer to levels obtained when vector was applied to the basolateral membrane. Moreover, GPI-CAR facilitated gene transfer of the cystic fibrosis transmembrane conductance regulator to cystic fibrosis airway epithelia, correcting the Cl(-) transport defect. In contrast, when we expressed wild-type CAR it localized to the basolateral membrane and failed to increase apical gene transfer. Only a small amount of Tailless-CAR resided in the apical membrane, and the effects on apical virus binding and gene transfer were minimal. These data indicate that binding of adenovirus to an apical membrane receptor is sufficient to mediate effective gene transfer to human airway epithelia and that the cytoplasmic domain of CAR is not required for this process. The results suggest that targeting apical receptors in differentiated airway epithelia may be sufficient for gene transfer in the genetic disease cystic fibrosis. PMID:11462042

  11. Apical Localization of the Coxsackie-Adenovirus Receptor by Glycosyl-Phosphatidylinositol Modification Is Sufficient for Adenovirus-Mediated Gene Transfer through the Apical Surface of Human Airway Epithelia

    PubMed Central

    Walters, Robert W.; van't Hof, Wouter; Yi, Su Min P.; Schroth, Mary K.; Zabner, Joseph; Crystal, Ronald G.; Welsh, Michael J.

    2001-01-01

    In well-differentiated human airway epithelia, the coxsackie B and adenovirus type 2 and 5 receptor (CAR) resides primarily on the basolateral membrane. This location may explain the observation that gene transfer is inefficient when adenovirus vectors are applied to the apical surface. To further test this hypothesis and to investigate requirements and barriers to apical gene transfer to differentiated human airway epithelia, we expressed CAR in which the transmembrane and cytoplasmic tail were replaced by a glycosyl-phosphatidylinositol (GPI) anchor (GPI-CAR). As controls, we expressed wild-type CAR and CAR lacking the cytoplasmic domain (Tailless-CAR). All three constructs enhanced gene transfer with similar efficiencies in fibroblasts. In airway epithelia, GPI-CAR localized specifically to the apical membrane, where it bound adenovirus and enhanced gene transfer to levels obtained when vector was applied to the basolateral membrane. Moreover, GPI-CAR facilitated gene transfer of the cystic fibrosis transmembrane conductance regulator to cystic fibrosis airway epithelia, correcting the Cl− transport defect. In contrast, when we expressed wild-type CAR it localized to the basolateral membrane and failed to increase apical gene transfer. Only a small amount of Tailless-CAR resided in the apical membrane, and the effects on apical virus binding and gene transfer were minimal. These data indicate that binding of adenovirus to an apical membrane receptor is sufficient to mediate effective gene transfer to human airway epithelia and that the cytoplasmic domain of CAR is not required for this process. The results suggest that targeting apical receptors in differentiated airway epithelia may be sufficient for gene transfer in the genetic disease cystic fibrosis. PMID:11462042

  12. Transport of human adenoviruses in porous media

    NASA Astrophysics Data System (ADS)

    Kokkinos, Petros; Syngouna, Vasiliki I.; Tselepi, Maria A.; Bellou, Maria; Chrysikopoulos, Constantinos V.; Vantarakis, Apostolos

    2015-04-01

    Groundwater may be contaminated with infective human enteric viruses from various wastewater discharges, sanitary landfills, septic tanks, agricultural practices, and artificial groundwater recharge. Coliphages have been widely used as surrogates of enteric viruses, because they share many fundamental properties and features. Although a large number of studies focusing on various factors (i.e. pore water solution chemistry, fluid velocity, moisture content, temperature, and grain size) that affect biocolloid (bacteria, viruses) transport have been published over the past two decades, little attention has been given toward human adenoviruses (hAdVs). The main objective of this study was to evaluate the effect of pore water velocity on hAdV transport in water saturated laboratory-scale columns packed with glass beads. The effects of pore water velocity on virus transport and retention in porous media was examined at three pore water velocities (0.39, 0.75, and 1.22 cm/min). The results indicated that all estimated average mass recovery values for hAdV were lower than those of coliphages, which were previously reported in the literature by others for experiments conducted under similar experimental conditions. However, no obvious relationship between hAdV mass recovery and water velocity could be established from the experimental results. The collision efficiencies were quantified using the classical colloid filtration theory. Average collision efficiency, α, values decreased with decreasing flow rate, Q, and pore water velocity, U, but no significant effect of U on α was observed. Furthermore, the surface properties of viruses and glass beads were used to construct classical DLVO potential energy profiles. The results revealed that the experimental conditions of this study were unfavorable to deposition and that no aggregation between virus particles is expected to occur. A thorough understanding of the key processes governing virus transport is pivotal for public

  13. Adenovirus Dodecahedron, as a Drug Delivery Vector

    PubMed Central

    Zochowska, Monika; Paca, Agnieszka; Schoehn, Guy; Andrieu, Jean-Pierre; Chroboczek, Jadwiga; Dublet, Bernard; Szolajska, Ewa

    2009-01-01

    Background Bleomycin (BLM) is an anticancer antibiotic used in many cancer regimens. Its utility is limited by systemic toxicity and dose-dependent pneumonitis able to progress to lung fibrosis. The latter can affect up to nearly 50% of the total patient population, out of which 3% will die. We propose to improve BLM delivery by tethering it to an efficient delivery vector. Adenovirus (Ad) dodecahedron base (DB) is a particulate vector composed of 12 copies of a pentameric viral protein responsible for virus penetration. The vector efficiently penetrates the plasma membrane, is liberated in the cytoplasm and has a propensity to concentrate around the nucleus; up to 300000 particles can be observed in one cell in vitro. Principal Findings Dodecahedron (Dd) structure is preserved at up to about 50°C at pH 7–8 and during dialysis, freezing and drying in the speed-vac in the presence of 150 mM ammonium sulfate, as well as during lyophilization in the presence of cryoprotectants. The vector is also stable in human serum for 2 h at 37°C. We prepared a Dd-BLM conjugate which upon penetration induced death of transformed cells. Similarly to free bleomycin, Dd-BLM caused dsDNA breaks. Significantly, effective cytotoxic concentration of BLM delivered with Dd was 100 times lower than that of free bleomycin. Conclusions/Significance Stability studies show that Dds can be conveniently stored and transported, and can potentially be used for therapeutic purposes under various climates. Successful BLM delivery by Ad Dds demonstrates that the use of virus like particle (VLP) results in significantly improved drug bioavailability. These experiments open new vistas for delivery of non-permeant labile drugs. PMID:19440379

  14. Exercise-induced pulmonary hemorrhage in a nonathlete: case report and review of physiology.

    PubMed

    Diwakar, Amit; Schmidt, Gregory A

    2014-04-01

    The integrity of the pulmonary blood-gas barrier is vulnerable to intense exercise in elite athletes, similar to the phenomenon of exercise-induced pulmonary hemorrhage in thoroughbred racehorses. A 50-year-old previously healthy man presented with acute onset shortness of breath, dry cough, and hypoxemia after engaging in an extremely vigorous game of handball. CT scan of the chest showed diffuse patchy air-space disease. Bronchoalveolar lavage revealed diffuse alveolar hemorrhage. Infectious etiologies and bleeding diatheses were excluded by laboratory testing. Serological tests for ANCA-associated vasculitis, lupus, and Goodpasture's disease also were negative. A transthoracic echocardiogram was normal. The patient recovered completely on supportive therapy in less than 72 h. This case demonstrates strenuous exercise as a cause of diffuse alveolar hemorrhage in a previously healthy male with no apparent underlying cardiopulmonary disease. PMID:24532148

  15. Selective induction of toxicity to human cells expressing human immunodeficiency virus type 1 Tat by a conditionally cytotoxic adenovirus vector.

    PubMed Central

    Venkatesh, L K; Arens, M Q; Subramanian, T; Chinnadurai, G

    1990-01-01

    The human immunodeficiency viruses (HIVs) primarily infect CD4+ T lymphocytes, leading eventually to the development of a systemic immune dysfunction termed acquired immunodeficiency syndrome (AIDS). An attractive strategy to combat HIV-mediated pathogenesis would be to eliminate the initial pool of infected cells and thus prevent disease progression. We have engineered a replication-defective, conditionally cytotoxic adenovirus vector, Ad-tk, whose action is dependent on the targeted expression of the herpes simplex virus type 1 thymidine kinase gene (tk), cloned downstream of the HIV-1 long terminal repeat, in human cells expressing the HIV-1 transcriptional activator Tat. Infection of Tat-expressing human HeLa or Jurkat cells with Ad-tk resulted in high-level tk expression, which was not deleterious to the viability of these cells. However, in the presence of the antiherpetic nucleoside analog ganciclovir, Ad-tk infection resulted in a massive reduction in the viability of these Tat-expressing cell lines. As adenoviruses are natural passengers of the human lymphoid system, our results suggest adenovirus vector-based strategies for the targeted expression, under the control of cis-responsive HIV regulatory elements, of cytotoxic agents in HIV-infected cells for the therapy of HIV-mediated pathogenesis. Images PMID:2247444

  16. CD40 Ligand and GMCSF Coexpression Enhance the Immune Responses and Protective Efficacy of PCV2 Adenovirus Vaccine.

    PubMed

    Li, Delong; Huang, Yong; Du, Qian; Wang, Zhenyu; Chang, Lingling; Zhao, Xiaomin; Tong, Dewen

    2016-04-01

    Porcine circovirus 2 (PCV2) capsid protein (Cap) is the major structural protein that is responsible for neutralizing antibodies development and protective immunity, thus it is usually used to develop vaccines against porcine circovirus-associated disease (PCVAD). Porcine CD40 ligand (CD40L) and granulocyte-macrophage colony-stimulating factor (GMCSF) have positive immunostimulatory effects on immunocytes and have been applied in vaccine efficacy improvement as attractive adjuvant cytokines, respectively. However, whether these two cytokines can produce synergistic effect in vaccines still need to be further studied. In this study, porcine CD40L and GMCSF were inserted into recombinant adenoviruses to test the immunogenicity of PCV2 adenovirus vaccine in mice. Western blot and indirect immunofluorescence assay showed that Ad-Cap, Ad-CD40L-Cap, Ad-Cap-GMCSF, and Ad-CD40L-Cap-GMCSF were successfully constructed. Indirect ELISA and virus neutralizing assay showed that CD40L and GMCSF could enhance humoral immune responses, and PCV2 Cap-specific antibody titer and neutralizing activities were significantly higher in Ad-CD40L-Cap-GMCSF group than that in the other groups that just inserted either porcine CD40L or GMCSF in recombinant adenoviruses. Moreover, lymphocyte proliferation assay and cytokine release assay showed that CD40L and GMCSF enhanced the cellular immune responses of Ad-Cap, and had synergistic effects in lymphocyte proliferative activities and Th1-type cytokine production. Following PCV2 challenge, the viral loads in lungs of Ad-CD40L-Cap-GMCSF group were significantly lower compared with Ad-Cap, Ad-CD40L-Cap, and Ad-Cap-GMCSF group. Taken together, the results of this study demonstrated that CD40L and GMCSF could synergistically enhance the protective immune responses of PCV2 adenovirus vaccine, which would be used as a potent vaccine for the prevention and control of PCVAD. PMID:26982652

  17. Canine adenovirus type 1 and Pasteurella pneumotropica co‑infection in a puppy.

    PubMed

    Pintore, Maria Domenica; Corbellini, Debora; Chieppa, Maria Novella; Vallino Costassa, Elena; Florio, Caterina Lucia; Varello, Katia; Bozzetta, Elena; Adriano, Daniela; Decaro, Nicola; Casalone, Cristina; Iulini, Barbara

    2016-03-31

    In 2008, a 2 months-old male German shepherd was presented with fever, depression, and evident organic wasting. The puppy died within 48 hours after the onset of clinical signs. A complete necropsy was performed. Bacteriological examination of samples from the brain, lung, liver, spleen, and bone marrow tested positive for Pasteurella pneumotropica. Histopathology demonstrated in ammatory and vascular lesions in the central nervous system and internal organs. Canine adenovirus type 1 nucleic acid was detected by polymerase chain reaction in the frozen brain but not in the formalin- xed, para n-embedded liver and lung samples. The positive PCR was subsequently con rmed by indirect uorescent antibody testing of the para n-embedded brain and liver sections. Although the liver is the primary site of viral damage, these laboratory ndings suggest that Canine adenovirus type 1 infection should be included in the di erential diagnosis of neuropathological diseases in dogs and that adenoviral infections could promote septicaemia caused by opportunistic pathogens. PMID:27033531

  18. Metabolic flux profiling of MDCK cells during growth and canine adenovirus vector production

    PubMed Central

    Carinhas, Nuno; Pais, Daniel A. M.; Koshkin, Alexey; Fernandes, Paulo; Coroadinha, Ana S.; Carrondo, Manuel J. T.; Alves, Paula M.; Teixeira, Ana P.

    2016-01-01

    Canine adenovirus vector type 2 (CAV2) represents an alternative to human adenovirus vectors for certain gene therapy applications, particularly neurodegenerative diseases. However, more efficient production processes, assisted by a greater understanding of the effect of infection on producer cells, are required. Combining [1,2-13C]glucose and [U-13C]glutamine, we apply for the first time 13C-Metabolic flux analysis (13C-MFA) to study E1-transformed Madin-Darby Canine Kidney (MDCK) cells metabolism during growth and CAV2 production. MDCK cells displayed a marked glycolytic and ammoniagenic metabolism, and 13C data revealed a large fraction of glutamine-derived labelling in TCA cycle intermediates, emphasizing the role of glutamine anaplerosis. 13C-MFA demonstrated the importance of pyruvate cycling in balancing glycolytic and TCA cycle activities, as well as occurrence of reductive alphaketoglutarate (AKG) carboxylation. By turn, CAV2 infection significantly upregulated fluxes through most central metabolism, including glycolysis, pentose-phosphate pathway, glutamine anaplerosis and, more prominently, reductive AKG carboxylation and cytosolic acetyl-coenzyme A formation, suggestive of increased lipogenesis. Based on these results, we suggest culture supplementation strategies to stimulate nucleic acid and lipid biosynthesis for improved canine adenoviral vector production. PMID:27004747

  19. Enteric immunization with live adenovirus type 21 vaccine. II. Systemic and local immune responses following immunization.

    PubMed

    Scott, R M; Dudding, B A; Romano, S V; Russell, P K

    1972-03-01

    Studies of the immunologic responses following administration of a live, enteric-coated adenovirus (ADV) type 21 vaccine showed that nine of ten vaccinees and none of five controls developed neutralizing antibody. Antibody activity of serum and secretory immunoglobulins was assayed by using a (14)C-labeled ADV-21 antigen in a radioimmunodiffusion system. Increases in immunoglobulin M, A and G (IgM, IgA, IgG) activity were detected in sera from vaccinees but not in those from controls. IgA copro antibody activity was also shown in vaccinees but not in controls. Nasal secretions showed no detectable IgA antibody responses by this method. These studies show marked differences in serum and local IgA antibody activity in induced enteric ADV infection compared to previously reported responses after natural infection. The protective role of secretory IgA in adenovirus infections is obscure. However, absence of nasal IgA responses may indicate that protection against disease with enteric ADV vaccines depends primarily upon humoral antibody. PMID:4629075

  20. An Adenovirus Vector Incorporating Carbohydrate Binding Domains Utilizes Glycans for Gene Transfer

    PubMed Central

    Nakayama, Masaharu; Ak, Ferhat; Ugai, Hideyo; Curiel, David T.

    2013-01-01

    Background Vectors based on human adenovirus serotype 5 (HAdV-5) continue to show promise as delivery vehicles for cancer gene therapy. Nevertheless, it has become clear that therapeutic benefit is directly linked to tumor-specific vector localization, highlighting the need for tumor-targeted gene delivery. Aberrant glycosylation of cell surface glycoproteins and glycolipids is a central feature of malignant transformation, and tumor-associated glycoforms are recognized as cancer biomarkers. On this basis, we hypothesized that cancer-specific cell-surface glycans could be the basis of a novel paradigm in HAdV-5-based vector targeting. Methodology/Principal Findings As a first step toward this goal, we constructed a novel HAdV-5 vector encoding a unique chimeric fiber protein that contains the tandem carbohydrate binding domains of the fiber protein of the NADC-1 strain of porcine adenovirus type 4 (PAdV-4). This glycan-targeted vector displays augmented CAR-independent gene transfer in cells with low CAR expression. Further, we show that gene transfer is markedly decreased in cells with genetic glycosylation defects and by inhibitors of glycosylation in normal cells. Conclusions/Significance These data provide the initial proof-of-concept for HAdV-5 vector-mediated gene delivery based on the presence of cell-surface carbohydrates. Further development of this new targeting paradigm could provide targeted gene delivery based on vector recognition of disease-specific glycan biomarkers. PMID:23383334

  1. Characterization of the Antiglioma Effect of the Oncolytic Adenovirus VCN-01.

    PubMed

    Vera, Beatriz; Martínez-Vélez, Naiara; Xipell, Enric; Acanda de la Rocha, Arlet; Patiño-García, Ana; Saez-Castresana, Javier; Gonzalez-Huarriz, Marisol; Cascallo, Manel; Alemany, Ramón; Alonso, Marta M

    2016-01-01

    Despite the recent advances in the development of antitumor therapies, the prognosis for patients with malignant gliomas remains dismal. Therapy with tumor-selective viruses is emerging as a treatment option for this devastating disease. In this study we characterize the anti-glioma effect of VCN-01, an improved hyaluronidase-armed pRB-pathway-selective oncolytic adenovirus that has proven safe and effective in the treatment of several solid tumors. VCN-01 displayed a significant cytotoxic effect on glioma cells in vitro. In vivo, in two different orthotopic glioma models, a single intra-tumoral administration of VCN-01 increased overall survival significantly and led to long-term survivors free of disease. PMID:26808201

  2. Characterization of the Antiglioma Effect of the Oncolytic Adenovirus VCN-01

    PubMed Central

    Vera, Beatriz; Martínez-Vélez, Naiara; Xipell, Enric; Acanda de la Rocha, Arlet; Patiño-García, Ana; Saez-Castresana, Javier; Gonzalez-Huarriz, Marisol; Cascallo, Manel; Alemany, Ramón; Alonso, Marta M.

    2016-01-01

    Despite the recent advances in the development of antitumor therapies, the prognosis for patients with malignant gliomas remains dismal. Therapy with tumor-selective viruses is emerging as a treatment option for this devastating disease. In this study we characterize the anti-glioma effect of VCN-01, an improved hyaluronidase-armed pRB-pathway-selective oncolytic adenovirus that has proven safe and effective in the treatment of several solid tumors. VCN-01 displayed a significant cytotoxic effect on glioma cells in vitro. In vivo, in two different orthotopic glioma models, a single intra-tumoral administration of VCN-01 increased overall survival significantly and led to long-term survivors free of disease. PMID:26808201

  3. Cerebral amyloid angiopathy causing large contralateral hemorrhage during surgery for lobar hemorrhage: a case report.

    PubMed

    Arishima, Hidetaka; Neishi, Hiroyuki; Kodera, Toshiaki; Kitai, Ryuhei; Kikuta, Ken-ichiro

    2015-03-01

    We report a rare case of cerebral amyloid angiopathy (CAA) causing large contralateral hemorrhage during surgery for lobar hemorrhage. A 62-year-old woman presented with lobar hemorrhage in the left frontal and parietal lobes recurring over the previous 1 month. Because we could not detect the origin of the lobar hemorrhage, we performed a biopsy around the lobar hemorrhage site with the removal of a hematoma. During the surgery, we identified acute brain swelling without bleeding from the operative field. Intraoperative computed tomography demonstrated new large lobar hemorrhage of the right parietal lobe, which we could promptly remove. Specimens around hematomas on both sides were pathologically diagnosed as CAA on immunohistochemical examination. After the surgery, she suffered from lobar hemorrhage three times in the space of only 3 months. To the best of our knowledge, there has been no reported case of CAA causing intracranial hemorrhage of another lesion during surgery. Neurosurgeons should know a possibility of intraoperative hemorrhage in surgeries for lobar hemorrhage caused by CAA. PMID:25601180

  4. [Management of major postpartum hemorrhage].

    PubMed

    Nebout, Sophie; Merbai, Nadia; Faitot, Valentina; Keita, Hawa

    2014-02-01

    Postpartum hemorrhage (PPH) is defined by loss of greater than 500 mL of blood following vaginal delivery or 1,000 mL of blood following cesarean section, in the first 24 hours postpartum. Its incidence is up to 5% and the severe forms represent 1% of births. PPH is the first cause of obstetrical maternal mortality in France and 90% of these deaths are considered as preventable. Its management is multidisciplinary (obstetricians, anesthetists, midwives, biologists and interventional radiologists), based on treatment protocols where time is a major prognosis factor. In case of failure of the initial measures (oxytocin, manual placenta removal, uterus and birth canal examination), the management of severe forms includes active resuscitation (intravenous fluids, blood transfusion, vasoactive drugs), haemostatic interventions (sulprostone, tamponnade and haemostatic suture, surgical procedures and arterial embolization) and the correction of any potential coagulopathy (administration of blood products and haemostatic agents). PMID:24373716

  5. [Intracerebral hemorrhage associated with nephrotic syndrome-Prevalemce and clinical characteristics].

    PubMed

    Kono, Ryuhei; Iwaki, Hirotaka; Takeshima, Shinichi; Shimoe, Yutaka; Ota, Shinzo; Kuriyama, Masaru

    2016-01-01

    Of the 11,161 cases of stroke observed for over 9 years, 21 cases in which both levels of serum albumin and cholesterol were < 3 g/dl and > 250 mg/dl, respectively, were identified. Out of these 21 cases, cases of severe proteinuria, i.e., nephrotic syndrome were selected. These included 10 cases of arterial ischemic thrombosis, 2 cases of cerebral venous sinus thrombosis, and 4 cases of intracerebral hemorrhage. The incidence of intracerebral hemorrhage associated with nephrotic syndrome was 0.18% of total stroke or 0.036% intracerebral hemorrhage. Nephrotic syndrome essentially induced a hypercoagulable state. The 4 cases with intracerebral hemorrhage associated with nephrotic syndrome, however, had strong risk factors for intracerebral hemorrhage, suggesting that they overcame the risk for thrombophilia. The diseases associated with the nephrotic syndrome were diabetic nephropathy and amyloidosis in 3 cases and in 1 case, respectively. The nephrotic syndrome tends to be associated with a risk for venous or arterial thrombosis. In addition, we must pay attention to intracerebral hemorrhage associated with nephrotic syndrome in cases of stroke. PMID:26887837

  6. Neurovascular Manifestations in Hereditary Hemorrhagic Telangiectasia: Imaging Features and Genotype-Phenotype Correlations

    PubMed Central

    Krings, Timo; Kim, Helen; Power, Sarah; Nelson, Jeffrey; Faughnan, Marie; Young, William L.; Terbrugge, Karel G.

    2015-01-01

    BACKGROUND AND PURPOSE Hereditary hemorrhagic telangiectasia is an autosomal dominant disease that presents in 10%–20% of patients with various brain vascular malformations. We aimed to report the radiologic features (phenotype) and the genotype-phenotype correlations of brain vascular malformations in hereditary hemorrhagic telangiectasia. MATERIALS AND METHODS Demographic, clinical, genotypic and imaging information of 75 HHT patients with hereditary hemorrhagic telangiectasia with brain arteriovenous malformations enrolled in the Brain Vascular Malformation Consortium from 2010 to 2012 were reviewed. RESULTS Non-shunting, small, superficially located conglomerates of enhancing vessels without enlarged feeding arteries or draining veins called “capillary vascular malformations” were the most commonly observed lesion (46 of 75 patients; 61%), followed by shunting “nidus-type” brain AVMs that were typically located superficially with a low Spetzler-Martin Grade and a small size (32 of 75 patients; 43%). Direct high-flow fistulous arteriovenous shunts were present in 9 patients (12%). Other types of vascular malformations (dural AVF and developmental venous anomalies) were present in 1 patient each. Multiplicity of vascular malformations was seen in 33 cases (44%). No statistically significant correlation was observed between hereditary hemorrhagic telangiectasia gene mutation and lesion type or lesion multiplicity. CONCLUSIONS Depending on their imaging features, brain vascular malformations in hereditary hemorrhagic telangiectasia can be subdivided into brain AVF, nidus-type AVM, and capillary vascular malformations, with the latter being the most common phenotype in hereditary hemorrhagic telangiectasia. No genotype-phenotype correlation was observed among patients with this condition. PMID:25572952

  7. Intraparenchymal hemorrhage segmentation from clinical head CT of patients with traumatic brain injury

    NASA Astrophysics Data System (ADS)

    Roy, Snehashis; Wilkes, Sean; Diaz-Arrastia, Ramon; Butman, John A.; Pham, Dzung L.

    2015-03-01

    Quantification of hemorrhages in head computed tomography (CT) images from patients with traumatic brain injury (TBI) has potential applications in monitoring disease progression and better understanding of the patho-physiology of TBI. Although manual segmentations can provide accurate measures of hemorrhages, the processing time and inter-rater variability make it infeasible for large studies. In this paper, we propose a fully automatic novel pipeline for segmenting intraparenchymal hemorrhages (IPH) from clinical head CT images. Unlike previous methods of model based segmentation or active contour techniques, we rely on relevant and matching examples from already segmented images by trained raters. The CT images are first skull-stripped. Then example patches from an "atlas" CT and its manual segmentation are used to learn a two-class sparse dictionary for hemorrhage and normal tissue. Next, for a given "subject" CT, a subject patch is modeled as a sparse convex combination of a few atlas patches from the dictionary. The same convex combination is applied to the atlas segmentation patches to generate a membership for the hemorrhages at each voxel. Hemorrhages are segmented from 25 subjects with various degrees of TBI. Results are compared with segmentations obtained from an expert rater. A median Dice coefficient of 0.85 between automated and manual segmentations is achieved. A linear fit between automated and manual volumes show a slope of 1.0047, indicating a negligible bias in volume estimation.

  8. A Case of Spontaneous Postpartum Thyroid Hemorrhage Leading to Upper Airway Obstruction

    PubMed Central

    Hristov, Boris D.; Borrego, Robert; Harding, Patricia A.; Hristov, Dimiter B.

    2016-01-01

    Patient: Female, 36 Final Diagnosis: Thyroid hemorrhage Symptoms: Shortness of breath Medication: — Clinical Procedure: Thyroidectomy Specialty: Surgery Objective: Rare disease Background: Spontaneous goiter hemorrhage is a rare entity that can lead to life-threatening respiratory compromise. Goiter hemorrhages are usually due to effects of anticoagulation or neoplastic processes. The hormonal effects of pregnancy may also lead to such life-threatening goiter hemorrhages in the immediate postpartum period. Case Report: We report the case of a 36-year-old woman who complained of progressive neck swelling as well as eventual shortness of breath in the immediate postpartum period. Computed tomography scans and ultrasound of the neck revealed an enlarged and heterogenous thyroid with airway compression. The patient underwent an emergent subtotal thyroidectomy to alleviate the mass effect on the airway. Upon resection, the thyroid was noted to contain a goiter hemorrhage with no signs of neoplastic degeneration on pathology. Conclusions: Pregnancy is a known hormonal stressor that routinely increases the size of the thyroid and also predisposes patients to goiter formation. In rare cases, thyroid goiters may be predisposed to hemorrhage, causing airway obstruction and necessitating urgent surgical intervention. PMID:27012654

  9. Plasmaphresis therapy for pulmonary hemorrhage in a pediatric patient with IgA nephropathy

    PubMed Central

    Yim, Dae-Kyoon; Lee, Sang-Taek

    2015-01-01

    IgA nephropathy usually presents as asymptomatic microscopic hematuria or proteinuria or episodic gross hematuria after upper respiratory infection. It is an uncommon cause of end-stage renal failure in childhood. Pulmonary hemorrhage associated with IgA nephropathy is an unusual life-threatening manifestation in pediatric patients and is usually treated with aggressive immunosuppression. Pulmonary hemorrhage and renal failure usually occur concurrently, and the pulmonary manifestation is believed to be caused by the same immune process. We present the case of a 14-year-old patient with IgA nephropathy who had already progressed to end-stage renal failure in spite of immunosuppression and presented with pulmonary hemorrhage during oral prednisone treatment. His lung disease was comparable to diffuse alveolar hemorrhage and was successfully treated with plasmapheresis followed by oral prednisone. This case suggests that pulmonary hemorrhage may develop independently of renal manifestation, and that plasmapheresis should be considered as adjunctive therapy to immunosuppressive medication for treating IgA nephropathy with pulmonary hemorrhage. PMID:26576186

  10. Latent class analysis of diagnostic tests for adenovirus, Bordetella pertussis and influenza virus infections in German adults with longer lasting coughs.

    PubMed

    Sobotzki, C; Riffelmann, M; Kennerknecht, N; Hülsse, C; Littmann, M; White, A; Von Kries, R; Wirsing VON König, C H

    2016-03-01

    Laboratory tests in adult outpatients with longer lasting coughs to identify a potential causal pathogen are rarely performed, and there is no gold standard for these diagnostic tests. While the diagnostic validity of serological tests for pertussis is well established their potential contribution for diagnosing adenovirus and influenza virus A and B infections is unclear. A sentinel study into the population-based incidence of longer lasting coughs in adults was done in Rostock (former East Germany) and Krefeld (former West Germany). A total of 971 outpatients who consulted general practitioners or internists were included. Inclusion criteria were coughing for ⩾1 week and no chronic respiratory diseases. We evaluated the performance of polymerase chain reaction (PCR) as well as IgG and IgA serology, applying a latent class model for diagnosing infections with adenovirus, B. pertussis, and influenza virus A and B. The adult outpatients first sought medical attention when they had been coughing for a median of 3 weeks. In this situation, direct detection of infectious agents by PCR had a low sensitivity. Modelling showed that additional serological tests equally improved sensitivity and specificity for diagnosis for adenovirus, B. pertussis and influenza virus A and B infections. The combination of serology and PCR may improve the overall performance of diagnostic tests for B. pertussis and also for adenovirus, and influenza virus A and B infections. PMID:26380914

  11. Bioaccumulation of animal adenoviruses in the pink shrimp.

    PubMed

    Luz, Roger B; Staggemeier, Rodrigo; Fabres, Rafael B; Soliman, Mayra C; Souza, Fernanda G; Gonçalves, Raoni; Fausto, Ivone V; Rigotto, Caroline; Heinzelmann, Larissa S; Henzel, Andréia; Fleck, Juliane D; Spilki, Fernando R

    2015-01-01

    Adenoviruses are among the most promising viral markers of fecal contamination. They are frequently found in the water, sediment and soil of regions impacted by human activity. Studies of the bioaccumulation of enteric viruses in shrimp are scarce. The cities located in the northern coast of the lake systems in Southern Brazil have high urbanization and intensive farming rates, and poor sewage collection and treatment. One hundred (n = 100) Farfantepenaeus paulensis pink-shrimp specimens and 48 water samples were collected from coastal lagoons between June 2012 and May 2013. Water samples were concentrated and the shrimp, mashed. After DNA extraction, samples were analyzed by real time polymerase chain reaction (qPCR) in order to detect and quantify viral genomes. Thirty-five percent of shrimp samples were positive for contamination, predominantly by avian adenoviruses. A total of 91.7% of water samples contained adenoviruses DNA, with the human form being the most frequent. Our results provided evidence of significant bioaccumulation of adenoviruses in shrimp, showing the extent of the impact of fecal pollution on aquatic ecosystems. PMID:26413052

  12. Bioaccumulation of animal adenoviruses in the pink shrimp

    PubMed Central

    Luz, Roger B.; Staggemeier, Rodrigo; Fabres, Rafael B.; Soliman, Mayra C.; Souza, Fernanda G.; Gonçalves, Raoni; Fausto, Ivone V.; Rigotto, Caroline; Heinzelmann, Larissa S.; Henzel, Andréia; Fleck, Juliane D.; Spilki, Fernando R.

    2015-01-01

    Adenoviruses are among the most promising viral markers of fecal contamination. They are frequently found in the water, sediment and soil of regions impacted by human activity. Studies of the bioaccumulation of enteric viruses in shrimp are scarce. The cities located in the northern coast of the lake systems in Southern Brazil have high urbanization and intensive farming rates, and poor sewage collection and treatment. One hundred (n = 100) Farfantepenaeus paulensis pink-shrimp specimens and 48 water samples were collected from coastal lagoons between June 2012 and May 2013. Water samples were concentrated and the shrimp, mashed. After DNA extraction, samples were analyzed by real time polymerase chain reaction (qPCR) in order to detect and quantify viral genomes. Thirty-five percent of shrimp samples were positive for contamination, predominantly by avian adenoviruses. A total of 91.7% of water samples contained adenoviruses DNA, with the human form being the most frequent. Our results provided evidence of significant bioaccumulation of adenoviruses in shrimp, showing the extent of the impact of fecal pollution on aquatic ecosystems. PMID:26413052

  13. Low seroprevalent species D adenovirus vectors as influenza vaccines.

    PubMed

    Weaver, Eric A; Barry, Michael A

    2013-01-01

    Seasonal and pandemic influenza remains a constant threat. While standard influenza vaccines have great utility, the need for improved vaccine technologies have been brought to light by the 2009 swine flu pandemic, highly pathogenic avian influenza infections, and the most recent early and widespread influenza activity. Species C adenoviruses based on serotype 5 (AD5) are potent vehicles for gene-based vaccination. While potent, most humans are already immune to this virus. In this study, low seroprevalent species D adenoviruses Ad26, 28, and 48 were cloned and modified to express the influenza virus A/PR/8/34 hemagglutinin gene for vaccine studies. When studied in vivo, these species D Ad vectors performed quite differently as compared to species C Ad vectors depending on the route of immunization. By intramuscular injection, species D vaccines were markedly weaker than species C vaccines. In contrast, the species D vaccines were equally efficient as species C when delivered mucosally by the intranasal route. Intranasal adenovirus vaccine doses as low as 10(8) virus particles per mouse induced complete protection against a stringent lethal challenge dose of influenza. These data support translation of species D adenoviruses as mucosal vaccines and highlight the fundamental effects of differences in virus tropism on vaccine applications. PMID:23991187

  14. Serologic and hexon phylogenetic analysis of ruminant adenoviruses

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The objectives of this study were to determine the antigenic relationship among ruminant adenoviruses and determine their phylogenetic relationship based on the deduced hexon gene amino acid sequence. Results of reciprocal cross-neutralization tests demonstrated antigenic relationships in either on...

  15. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  16. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  17. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  18. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  19. 21 CFR 866.3020 - Adenovirus serological reagents.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Adenovirus serological reagents. 866.3020 Section 866.3020 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES IMMUNOLOGY AND MICROBIOLOGY DEVICES Serological Reagents § 866.3020...

  20. Intracerebral hemorrhage due to developmental venous anomalies.

    PubMed

    Li, Xiaodi; Wang, Yuzhou; Chen, Wenming; Wang, Wensheng; Chen, Kaizhe; Liao, Huayin; Lu, Jianjun; Li, Zhigang

    2016-04-01

    Developmental venous anomalies (DVA) and cavernous malformations (CM) are a common form of mixed vascular malformation. The relationship between DVA, CM and hemorrhage is complicated. It is important to differentiate hemorrhagic CM and hemorrhagic DVA. A retrospective review of all patients with acute spontaneous intracerebral hemorrhages (ICH) between 1 May 2008 and 1 May 2013 was performed. ICH due to DVA or CM were identified and compared for demographic features, clinical symptoms, neurological deficits, and radiological findings. A total of 1706 patients with acute spontaneous ICH were admitted to our hospital during the study period. Among these, 10 (0.59%) were caused by DVA and 42 (2.47%) were caused by CM. No significant differences were found in age (p=0.252) or sex ratio (p=1.000) between the two groups. Compared with CM-induced ICH, DVA-induced ICH were characterized by cerebellar predominance (p=0.000) and less severe neurological deficits (p=0.008). Infratentorial hemorrhagic DVA are characterized by cerebellar predominance and benign clinical course. Infratentorial hemorrhagic CM are mainly located in the brainstem. DVA should be given suspected rather than CM when considering the etiology of a cerebellar hemorrhage, especially in young adults. PMID:26803466

  1. Paraplegia caused by aortic coarctation complicated with spinal epidural hemorrhage.

    PubMed

    Tsai, Yi-Da; Hsu, Chin-Wang; Hsu, Chia-Ching; Liao, Wen-I; Chen, Sy-Jou

    2016-03-01

    Aortic coarctation complicated with spinal artery aneurysm rupture is exceptionally rare and can be source of intraspinal hemorrhage with markedly poor prognosis. A 21-year-old man visited the emergency department because of chest and back pain along with immobility of bilateral lower limbs immediately after he woke up in the morning. Complete flaccid paraplegia and hypoesthesia in dermatome below bilateral T3 level and pain over axial region from neck to lumbar region were noted. A computed tomography excluded aortic dissection. Magnetic resonance imaging revealed a fusiform lesion involving the anterior epidural space from C7 to T2 level suspected of epidural hemorrhage, causing compression of spinal cord. He started intravenous corticosteroid but refused operation concerning the surgical benefits. Severe chest pain occurred with newly onset right bundle branch block that developed the other day. Coronary artery angiography revealed myocardial bridge of left anterior descending coronary artery at middle third and coarctation of aorta. He underwent thoracic endovascular aortic repair uneventfully. The patient was hemodynamically stable but with slow improvement in neurologic recovery of lower limbs. Aortic coarcation can cause paralysis by ruptured vascular aneurysms with spinal hemorrhage and chest pain that mimics acute aortic dissection. A history of hypertension at young age and aortic regurgitated murmurs may serve as clues for further diagnostic studies. Cautious and prudent evaluation and cross disciplines cares are essential for diagnosis and successful management of the disease. PMID:26275629

  2. Acute hemorrhagic edema of infancy and common mimics.

    PubMed

    Homme, James L; Block, Jason M

    2016-05-01

    Acute hemorrhagic edema of infancy (AHEI) is a rare acute benign cutaneous leukocytoclastic vasculitis affecting children younger than 24 months of age. Its presentation can be confused with those of urticaria, erythema multiforme, Henoch-Schönlein purpura, idiopathic thrombocytopenia,meningococcemia, Kawasaki disease, and drug rash. We present 2 cases of acute hemorrhagic edema of infancy, discuss the characteristics of AHEI, and compare and contrast AHEI with similar dermatologic presentations. This review provides emergency physicians with the basic knowledge necessary to easily recognize AHEI as a distinct clinical entity. The patients were 19- and 23-month-old females who presented to the pediatric emergency department at St Mary's Hospital,Mayo Clinic in Rochester, Minnesota, with impressive purpuric rashes and edema of the hands and feet after preceding upper respiratory tract infections. Both children had benign courses with complete resolution of clinical findings. These 2 cases typify the presentation of AHEI.Acute hemorrhagic edema of infancy presents with characteristic purpuric lesions and extremity edema. The emergency physician's recognition of these presenting characteristics will help diagnose AHEI, avoid unnecessary procedures and tests, and aid in counseling the patient's parents. PMID:26774545

  3. Beneficial Effect of Hyperbaric Oxygenation After Neonatal Germinal Matrix Hemorrhage

    PubMed Central

    Lekic, Tim; Manaenko, Anatol; Rolland, William; Ostrowski, Robert P.; Virbel, Kelly; Tang, Jiping

    2013-01-01

    Background Germinal matrix hemorrhage (GMH) is a potentially devastating neurological disease of very low birth weight premature infants. This leads to post-hemorrhagic hydrocephalus, cerebral palsy, and mental retardation. Hyperbaric oxygen (HBO) treatment is a broad neuroprotectant after brain injury. This study investigated the therapeutic effect of HBO after neonatal GMH. Methods Neonatal rats underwent stereotaxic infusion of clostridial collagenase into the right germinal matrix (anterior caudate) brain region. Cognitive function was assessed at 3 weeks, and then sensorimotor, cerebral, cardiac, and splenic growths were measured 1 week thereafter. Results Hyperbaric oxygen (HBO) treatment markedly improved upon the mental retardation and cerebral palsy outcome measurements in rats at the juvenile developmental stage. The administration of HBO early after neonatal GMH also normalized brain atrophy, splenomegaly, and cardiac hypertrophy 1 month after injury. Conclusion This study supports the role of hyperbaric oxygen (HBO) treatment in the early period after neonatal GMH. HBO is an effective strategy to help protect the infant’s brain from the post-hemorrhagic consequences of brain atrophy, mental retardation, and cerebral palsy. Further studies are necessary to determine the mechanistic basis of these neuroprotective effects. PMID:21725764

  4. SLE presenting as multiple hemorrhagic complications.

    PubMed

    Abdulla, M C; Alungal, J; Hashim, S; Ali, M M; Musambil, M

    2015-09-01

    A 24 year old female with hereditary spastic paraplegia presented with intermittent headache for one year. She also had lower abdominal pain and vomiting for two months. She was pale, had icterus and mild splenomegaly. On diagnostic evaluation she was found to have hemolytic anemia, thrombocytopenia and bilateral adrenal, subdural, soft tissue (scalp and orbit) hemorrhages due to systemic lupus erythematosus (SLE). However, antiphospholipid syndrome (APS) antibodies were negative. Bilateral adrenal hemorrhage without associated APS is a rare phenomenon in SLE. We describe a case of SLE presenting with sequence of rare hemorrhagic complications in concert. PMID:25716420

  5. [Preparation of Recombinant Human Adenoviruses Labeled with miniSOG].

    PubMed

    Zou, Xiaohui; Xiao, Rong; Guo, Xiaojuan; Qu, Jianguo; Lu, Zhuozhuang; Hong, Tao

    2016-01-01

    We wished to study the intracellular transport of adenoviruses. We constructed a novel recombinant adenovirus in which the structural protein IX was labeled with a mini-singlet oxygen generator (miniSOG). The miniSOG gene was synthesized by overlapping extension polymerase chain reaction (PCR), cloned to the pcDNA3 vector, and expressed in 293 cells. Activation of miniSOG generated sufficient numbers of singlet oxygen molecules to catalyze polymerization of diaminobenzidine into an osmiophilic reaction product resolvable by transmission electron microscopy (TEM). To construct miniSOG-labelled recombinant adenoviruses, the miniSOG gene was subcloned downstream of the IX gene in a pShuttle plasmid. Adenoviral plasmid pAd5-IXSOG was generated by homologous recombination of the modified shuttle plasmid (pShuttle-IXSOG) with the backbone plasmid (pAdeasy-1) in the BJ5183 strain of Eschericia coli. Adenovirus HAdV-5-IXSOG was rescued by transfection of 293 cells with the linearized pAd5-IXSOG. After propagation, virions were purified using the CsC1 ultracentrifugation method. Finally, HAdV-5-IXSOG in 2.0 mL with a particle titer of 6 x 1011 vp/mL was obtained. Morphology of HAdV-5-IXSOG was verified by TEM. Fusion of IX with the miniSOG gene was confirmed by PCR. In conclusion, miniSOG-labeled recombinant adenoviruses were constructed, which could be valuable tools for virus tracking by TEM. PMID:27295881

  6. Conserved Sequences at the Origin of Adenovirus DNA Replication

    PubMed Central

    Stillman, Bruce W.; Topp, William C.; Engler, Jeffrey A.

    1982-01-01

    The origin of adenovirus DNA replication lies within an inverted sequence repetition at either end of the linear, double-stranded viral DNA. Initiation of DNA replication is primed by a deoxynucleoside that is covalently linked to a protein, which remains bound to the newly synthesized DNA. We demonstrate that virion-derived DNA-protein complexes from five human adenovirus serological subgroups (A to E) can act as a template for both the initiation and the elongation of DNA replication in vitro, using nuclear extracts from adenovirus type 2 (Ad2)-infected HeLa cells. The heterologous template DNA-protein complexes were not as active as the homologous Ad2 DNA, most probably due to inefficient initiation by Ad2 replication factors. In an attempt to identify common features which may permit this replication, we have also sequenced the inverted terminal repeated DNA from human adenovirus serotypes Ad4 (group E), Ad9 and Ad10 (group D), and Ad31 (group A), and we have compared these to previously determined sequences from Ad2 and Ad5 (group C), Ad7 (group B), and Ad12 and Ad18 (group A) DNA. In all cases, the sequence around the origin of DNA replication can be divided into two structural domains: a proximal A · T-rich region which is partially conserved among these serotypes, and a distal G · C-rich region which is less well conserved. The G · C-rich region contains sequences similar to sequences present in papovavirus replication origins. The two domains may reflect a dual mechanism for initiation of DNA replication: adenovirus-specific protein priming of replication, and subsequent utilization of this primer by host replication factors for completion of DNA synthesis. Images PMID:7143575

  7. Functional Heterogeneity of Virions in Human Adenovirus Types 2 and 12

    PubMed Central

    Rainbow, Andrew J.; Mak, Stanley

    1970-01-01

    Purified preparations of adenovirus types 2 and 12 were used to infect KB cells at different input multiplicities. The resulting infected cultures were scored for inclusion body formation, production of infectious centers, and cloning efficiency. Both preparations were found to contain some defective particles capable of preventing a cell from cloning but unable to induce inclusion bodies or form plaques. The proportion of such defective particles in adenovirus 12 was about 10 times that in adenovirus 2. At high input multiplicities, the percentage of cells displaying an inclusion body was less than that predicted by the Poisson distribution and reached a maximum of 40 to 60% for adenovirus 2 and 12 to 15% for adenovirus 12. This reduction may be due to interference by large numbers of non-plaque-producing particles infecting each cell. The per cent of cells forming infectious centers was substantially greater for adenovirus 2 than for adenovirus 12 when compared at the same input plaque-forming units, reaching a maximum of 35 to 73% for adenovirus 2 and 5 to 10% for adenovirus 12. The low value for adenovirus 12 may be a result of the same interference phenomenon. Images PMID:4194167

  8. Detection of viral hemorrhagic septicemia virus

    USGS Publications Warehouse

    Winton, James; Kurath, Gael; Batts, William

    2007-01-01

    Viral hemorrhagic septicemia virus (VHSV) is considered to be one of the most important viral pathogens of finfish and is listed as reportable by many nations and international organizations (Office International des Epizooties 2006). Prior to 1988, VHSV was thought to be limited to Europe (Wolf 1988; Smail 1999). Subsequently, it was shown that the virus is endemic among many marine and anadromous fish species in both the Pacific and Atlantic Oceans (Meyers and Winton 1995; Skall et al. 2005). Genetic analysis reveals that isolates of VHSV can be divided into four genotypes that generally correlate with geographic location with the North American isolates generally falling into VHSV Genotype IV (Snow et al. 2004). In 2005-2006, reports from the Great Lakes region indicated that wild fish had experienced disease or, in some cases, very large die-offs from VHSV (Elsayed et al. 2006, Lumsden et al. 2007). The new strain from the Great Lakes, now identified as VHSV Genotype IVb, appears most closely related to isolates of VHSV from mortalities that occurred during 2000-2004 in rivers and near-shore areas of New Brunswick and Nova Scotia, Canada (Gagne et al. 2007). The type IVb isolate found in the Great Lakes region is the only strain outside of Europe that has been associated with significant mortality in freshwater species.

  9. Genomic organization and chromosomal localization of the human Coxsackievirus B-adenovirus receptor gene.

    PubMed

    Bowles, K R; Gibson, J; Wu, J; Shaffer, L G; Towbin, J A; Bowles, N E

    1999-10-01

    Myocarditis and dilated cardiomyopathy (DCM) are common causes of morbidity and mortality in children. Many studies have implicated the enteroviruses and, particularly, the Coxsackievirus-B family as etiologic agents of the acquired forms of these diseases. However, we have shown the group-C adenoviruses to be as commonly detected as enteroviruses in the myocardium of children and adults with these diseases. It has remained something of a conundrum why two such divergent virus families cause these diseases. The recent description of the common human Coxsackievirus B-adenovirus receptor (CAR) offers at least a partial explanation. In order to characterize the CAR gene, we screened a bacterial artificial chromosomal (BAC) library (RPCI11) using a polymerase chain reaction (PCR) product derived from the 3' end of the CAR cDNA sequence. This identified 13 BACs that were further characterized by PCR amplification of seven contiguous regions of the entire cDNA sequence. Eleven of the BACs were determined to encode pseudogenes while the other two BACs (131J5 and 246M1) encoded the presumed functional gene. PCR amplification of a monochromosomal hybrid panel indicated the presence of pseudogenes on chromosomes 15, 18, and 21 while the functional gene is encoded on chromosome 21. Fluorescence in situ hybridization analysis indicated that the gene is located at 21q11.2. DNA sequencing of BACs 131J5 and 246M1 revealed the presence of seven exons. The DNA sequences have been determined for each exon-intron boundary, and putative promoter sequences and transcription initiation sites identified. No consensus polyadenylation signal was identified. PMID:10543405

  10. Peribulbar anesthesia causing bilateral orbital hemorrhage

    PubMed Central

    Garft, Kyla; Burt, Peter; Burt, Benjamin

    2016-01-01

    We report a case of bilateral orbital hemorrhage as a complication of peribulbar anesthesia in a 78 year old man. Initially, unilateral orbital hemorrhage occurred but quickly spread to the contralateral side. Neuroophthalmological assessment revealed a proptosed tense globe with normal retinovascular findings. Visual acuity was adversely affected and this was conservatively managed with no lasting ophthalmic sequela. This patient’s case was reported as it illustrates an unusual complication of bilateral spread of orbital hemorrhage secondary to peribulbar anesthesia. It highlights how early ophthalmic assessment can ensure a good visual outcome in the setting of appropriate ophthalmic monitoring. The mechanisms of orbital hemorrhage spread and appropriate management options are discussed. PMID:27013899

  11. Human Hemorrhagic Pulmonary Leptospirosis: Pathological Findings and Pathophysiological Correlations

    PubMed Central

    De Brito, Thales; Aiello, Vera Demarchi; da Silva, Luis Fernando Ferraz; Gonçalves da Silva, Ana Maria; Ferreira da Silva, Wellington Luiz; Castelli, Jussara Bianchi; Seguro, Antonio Carlos

    2013-01-01

    Background Leptospirosis is a re-emerging zoonosis with protean clinical manifestations. Recently, the importance of pulmonary hemorrhage as a lethal complication of this disease has been recognized. In the present study, five human necropsies of leptospirosis (Weil‘s syndrome) with extensive pulmonary manifestations were analysed, and the antibodies expressed in blood vessels and cells involved in ion and water transport were used, seeking to better understand the pathophysiology of the lung injury associated with this disease. Principal Findings Prominent vascular damage was present in the lung microcirculation, with decreased CD34 and preserved aquaporin 1 expression. At the periphery and even inside the extensive areas of edema and intraalveolar hemorrhage, enlarged, apparently hypertrophic type I pneumocytes (PI) were detected and interpreted as a non-specific attempt of clearence of the intraalveolar fluid, in which ionic transport, particularly of sodium, plays a predominant role, as suggested by the apparently increased ENaC and aquaporin 5 expression. Connexin 43 was present in most pneumocytes, and in the cytoplasm of the more preserved endothelial cells. The number of type II pneumocytes (PII) was slightly decreased when compared to normal lungs and those of patients with septicemia from other causes, a fact that may contribute to the progressively low PI count, resulting in deficient restoration after damage to the alveolar epithelial integrity and, consequently, a poor outcome of the pulmonary edema and hemorrhage. Conclusions Pathogenesis of lung injury in human leptospirosis was discussed, and the possibility of primary non-inflammatory vascular damage was considered, so far of undefinite etiopathogenesis, as the initial pathological manifestation of the disease. PMID:23951234

  12. Hemorrhagic Fever Occurs After Intravenous, But Not After Intragastric, Inoculation of Rhesus Macaques With Lymphocytic Choriomeningitis Virus

    PubMed Central

    Lukashevich, Igor S.; Djavani, Mahmoud; Rodas, Juan D.; Zapata, Juan C.; Usborne, Amy; Emerson, Carol; Mitchen, Jacque; Jahrling, Peter B.; Salvato, Maria S.

    2008-01-01

    Arenaviruses can cause hemorrhagic fever and death in primates and guinea pigs, but these viruses are not highly pathogenic for most rodent carriers. In the United States, arenaviruses precipitated outbreaks of hepatitis in captive monkeys, and they present an emerging health threat in the tropical areas of Africa and South America. We describe infection of rhesus macaques with the prototype arenavirus, lymphocytic choriome-ningitis virus (LCMV), using the WE strain that has been known to cause both encephalopathy and multifocal hemorrhage. Five macaques were inoculated: two by the intravenous (i.v.) and three by the intragastric (i.g.) route. Whereas the two i.v.-inoculated monkeys developed signs and lesions consistent with fatal hemorrhagic fever, the i.g.-inoculated monkeys had an attenuated infection with no disease. Pathological signs of the primate i.v. infection differ significantly from guinea pig arenavirus infections and make this a superior model for human viral hemorrhagic disease. PMID:11992578

  13. A 45-Year-Old Man With Recurrent Dyspnea and Hemoptysis during Exercise: Exercise-Induced Pulmonary Hemorrhage/Edema

    PubMed Central

    Kim, Dae Sung; Lee, Minhyeok; Kwon, Oh Jung; Jeong, Inbeom; Son, Ji Woong; Na, Moon Jun

    2015-01-01

    A 45-year-old man presented with dyspnea and hemoptysis during exercise. A chest computed tomography (CT) revealed multifocal diffuse patchy ground glass opacity and interlobular septal thickening in both the lungs. Permeability pulmonary edema or pulmonary hemorrhage was suspected. Serologic studies for autoimmune disorders and vasculitis were negative. There was no laboratory evidence of coagulopathy, other hematopoietic disease or infectious disease. Considering correlation with exercise, we diagnosed exercise-induced pulmonary hemorrhage (EIPH) or exercise-induced pulmonary edema (EIPE). The patient was managed with antifibrinolytics, antibiotics, and antitussive agent. After a week, follow-up chest CT revealed completely resolved pulmonary hemorrhage. About 2 months after the first event, he visited again with dyspnea and hemoptysis during running. In the present study, we report a case of recurrent pulmonary hemorrhage after exercise. PMID:26508928

  14. Adenovirus Type 2-Simian Virus 40 Hybrid Population: Evidence for a Hybrid Deoxyribonucleic Acid Molecule and the Absence of Adenovirus-Encapsidated Circular Simian Virus 40 Deoxyribonucleic Acid

    PubMed Central

    Crumpacker, Clyde S.; Levin, Myron J.; Wiese, William H.; Lewis, Andrew M.; Rowe, Wallace P.

    1970-01-01

    The deoxyribonucleic acid (DNA) from the adenovirus-encapsidated particles of the adenovirus type 2 (Ad2)-simian virus 40 (SV40) hybrid population plaque variant (Ad2++ HEY), known to yield SV40 virus with high efficiency, was studied by equilibrium density centrifugation followed by ribonucleic acid-DNA hybridization employing virus-specific complementary ribonucleic acids synthesized in vitro. These techniques establish linkage between the Ad2 and SV40 components in the adenovirus-encapsidated particles of this population. The linkage is alkali-resistant and presumably covalent; thus, the Ad2 DNA and SV40 DNA are present in a hybrid molecule. Velocity centrifugation studies in alkaline sucrose gradients eliminated the possibility that supercoiled circular SV40 DNA is present in the adenovirus capsids. The DNA obtained from the adenovirus-encapsidated particles of the Ad2++ HEY population appears to consist of nonhybrid Ad2 DNA and Ad2-SV40 hybrid DNA molecules. PMID:4322081

  15. Predicting Hemorrhagic Transformation of Acute Ischemic Stroke

    PubMed Central

    Marsh, Elisabeth B.; Llinas, Rafael H.; Schneider, Andrea L.C.; Hillis, Argye E.; Lawrence, Erin; Dziedzic, Peter; Gottesman, Rebecca F.

    2016-01-01

    Abstract Hemorrhagic transformation (HT) increases the morbidity and mortality of ischemic stroke. Anticoagulation is often indicated in patients with atrial fibrillation, low ejection fraction, or mechanical valves who are hospitalized with acute stroke, but increases the risk of HT. Risk quantification would be useful. Prior studies have investigated risk of systemic hemorrhage in anticoagulated patients, but none looked specifically at HT. In our previously published work, age, infarct volume, and estimated glomerular filtration rate (eGFR) significantly predicted HT. We created the hemorrhage risk stratification (HeRS) score based on regression coefficients in multivariable modeling and now determine its validity in a prospectively followed inpatient cohort. A total of 241 consecutive patients presenting to 2 academic stroke centers with acute ischemic stroke and an indication for anticoagulation over a 2.75-year period were included. Neuroimaging was evaluated for infarct volume and HT. Hemorrhages were classified as symptomatic versus asymptomatic, and by severity. HeRS scores were calculated for each patient and compared to actual hemorrhage status using receiver operating curve analysis. Area under the curve (AUC) comparing predicted odds of hemorrhage (HeRS score) to actual hemorrhage status was 0.701. Serum glucose (P < 0.001), white blood cell count (P < 0.001), and warfarin use prior to admission (P = 0.002) were also associated with HT in the validation cohort. With these variables, AUC improved to 0.854. Anticoagulation did not significantly increase HT; but with higher intensity anticoagulation, hemorrhages were more likely to be symptomatic and more severe. The HeRS score is a valid predictor of HT in patients with ischemic stroke and indication for anticoagulation. PMID:26765425

  16. Hemorrhagic sarcoid pleural effusion: A rare entity

    PubMed Central

    Jha, Onkar; Nair, Vidya; Talwar, Deepak

    2016-01-01

    Involvement of pleura by sarcoidosis remains a rare manifestation and varies from pleural effusion, pneumothorax, pleural thickening, hydropneumothorax, trapped lung, hemothorax, or chylothorax. Sarcoid pleural effusions presenting as hemorrhagic effusions are even more rare. We report a case of active pulmonary sarcoidosis presenting as hemorrhagic pleural effusion requiring tissue diagnosis to rule out malignancy. The rarity of the presentation prompted us to report this case.

  17. Hemorrhagic sarcoid pleural effusion: A rare entity.

    PubMed

    Jha, Onkar; Nair, Vidya; Talwar, Deepak

    2016-01-01

    Involvement of pleura by sarcoidosis remains a rare manifestation and varies from pleural effusion, pneumothorax, pleural thickening, hydropneumothorax, trapped lung, hemothorax, or chylothorax. Sarcoid pleural effusions presenting as hemorrhagic effusions are even more rare. We report a case of active pulmonary sarcoidosis presenting as hemorrhagic pleural effusion requiring tissue diagnosis to rule out malignancy. The rarity of the presentation prompted us to report this case. PMID:27625449

  18. Pulmonary hemorrhage resulting from roller coaster.

    PubMed

    Yin, Ming; Tian, Qing; Shen, Hong

    2011-03-01

    Roller coasters are probably one of the more popular rides at amusement parks around the world, and there are few reported injuries. We report a case of symmetric diffuse upper lobe hemorrhage resulting from roller coaster in a previously healthy woman. The clinical course, management, and etiology of her case are discussed; and the literature is reviewed. To our knowledge, pulmonary hemorrhage in this setting has not yet been described. PMID:20825914

  19. Hemostatic status in liver transplantation: association between preoperative procoagulants/anticoagulants and postoperative hemorrhaging/thrombosis.

    PubMed

    Akamatsu, Nobuhisa; Sugawara, Yasuhiko; Nakazawa, Akiko; Nishioka, Yujiro; Kaneko, Junichi; Aoki, Taku; Sakamoto, Yoshihiro; Hasegawa, Kiyoshi; Kokudo, Norihiro

    2015-02-01

    The delicate rebalanced hemostatic status of liver transplant recipients may lead to both hemorrhagic and thrombotic tendencies in this population. The aim of this study was to investigate the association between pretransplant procoagulants/anticoagulants and posttransplant bleeding and thrombosis among living donor liver transplant recipients. The study subjects were 403 consecutive recipients with chronic liver disease. Perioperative variables, including preoperative values for procoagulants and anticoagulants, were assessed to determine their association with posttransplant hemorrhaging and thrombosis. There were 35 hemorrhagic complications (9%) and 21 thrombotic complications (5%). In logistic regression analyses, a higher Model for End-Stage Liver Disease score (P = 0.01) and a lower fibrinogen value (P < 0.001) were independently associated with hemorrhaging, whereas only a lower protein C value (P < 0.001) was independently associated with thrombosis. In a receiver operating characteristic analysis, a low preoperative protein C value (with the most accurate cutoff value being 25%) was a reliable predictor of thrombotic complications after liver transplantation (area under the curve = 0.921, P < 0.001, sensitivity = 0.9, specificity = 0.8). In conclusion, the decreases in both procoagulants and anticoagulants in liver transplant recipients may additively result in a delicate hemostatic balance and predispose patients to both hemorrhagic and thrombotic complications. A lower preoperative protein C value (<25%) was demonstrated to be a significant and reliable predictor of postoperative thrombotic complications in liver transplant recipients. PMID:25370801

  20. Dengue hemorrhagic fever and the kidney.

    PubMed

    Vachvanichsanong, Prayong; Thisyakorn, Usa; Thisyakorn, Chule

    2016-04-01

    Dengue virus infection (DVI)/dengue hemorrhagic fever (DHF) is a common febrile illness with a variety of severities. The mortality rate is high in dengue shock syndrome (DSS), caused by circulatory failure due to plasma leakage resulting in multi-organ failure. However, acute kidney injury (AKI) is rarely reported. In areas of endemic DVI, the prevalence of AKI due to DVI has been reported to be as high as 6.0 % in children with AKI, and 0.9 % in children with DVI who were admitted to a hospital. The mechanism of AKI in DVI is not clear. It may result from (a) direct injury as in other infectious diseases, (b) an indirect mechanism such as via the immune system, since DHF is an immunological disease, or (c) hypotensive DSS, leading in turn to reduced renal blood supply and renal failure. The mortality rates of DF/DHF, DSS and DHF/DSS-related AKI are <1 %, 12-44 %, and >60 %, respectively. Kidney involvement is not actually that rare, but is under-recognized and often only reported when microscopic hematuria, proteinuria, electrolyte imbalance, or even AKI is found. The prevalence of proteinuria and hematuria has been reported as high as 70-80 % in DVI. A correct diagnosis depends on basic investigations of kidney function such as urinalysis, serum creatinine and electrolytes. Although DVI-related renal involvement is treated supportively, it is still important to make an early diagnosis to prevent AKI and its complications, and if AKI does occur, dialysis may be required. Fortunately, in patients who recover, kidney function usually completely recovers as well. PMID:26699788