61 results on '"Urs Karrer"'
Search Results
2. Universal Admission Screening for SARS-CoV-2 Infections among Hospitalized Patients, Switzerland, 2020
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Thomas Scheier, Adrian Schibli, Geri Eich, Christian Rüegg, Frank Kube, Adrian Schmid, Urs Karrer, Aline Wolfensberger, Hugo Sax, and Peter W. Schreiber
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COVID-19 ,SARS-CoV-2 ,epidemiology ,emerging infections ,asymptomatic transmission ,PCR ,Medicine ,Infectious and parasitic diseases ,RC109-216 - Abstract
Switzerland began a national lockdown on March 16, 2020, in response to the rapid spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed the prevalence of SARS-CoV-2 infection among patients admitted to 4 hospitals in the canton of Zurich, Switzerland, in April 2020. These 4 acute care hospitals screened 2,807 patients, including 2,278 (81.2%) who did not have symptoms of coronavirus disease (COVID-19). Overall, 529 (18.8%) persons had >1 symptom of COVID-19, of whom 60 (11.3%) tested positive for SARS-CoV-2. Eight asymptomatic persons (0.4%) also tested positive for SARS-CoV-2. Our findings indicate that screening on the basis of COVID-19 symptoms, regardless of clinical suspicion, can identify most SARS-CoV-2–positive persons in a low-prevalence setting. more...
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- 2021
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Catalog
3. Organizing a COVID-19 triage unit: a Swiss perspective
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Georgios Peros, Ferda Gronki, Nadine Molitor, Michael Streit, Kiyoshi Sugimoto, Urs Karrer, Fabian Lunger, Michel Adamina, Stefan Breitenstein, and Tenzin Lamdark
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COVID ,COVID-19 ,Sars-CoV-2 ,triage ,Swiss ,Infectious and parasitic diseases ,RC109-216 ,Microbiology ,QR1-502 - Abstract
ABSTRACTBackground: With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. Methods: Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. Observations: A total of 1265 patients were screened between 10 March 2020 and 12 April 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p more...
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- 2020
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4. Primary immune responses are negatively impacted by persistent herpesvirus infections in older people: results from an observational study on healthy subjects and a vaccination trial on subjects aged more than 70 years old
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Francesco Nicoli, Emmanuel Clave, Kerstin Wanke, Amrei von Braun, Vincent Bondet, Cécile Alanio, Corinne Douay, Margaux Baque, Claire Lependu, Peggy Marconi, Karin Stiasny, Franz X. Heinz, Margot Muetsch, Darragh Duffy, Jacques Boddaert, Delphine Sauce, Antoine Toubert, Urs Karrer, and Victor Appay more...
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Naive T lymphocytes ,Thymus ,Elderly ,T-cell responses ,Vaccines ,Medicine ,Medicine (General) ,R5-920 - Abstract
Summary: Background: Advanced age is accompanied by a decline of immune functions, which may play a role in increased vulnerability to emerging pathogens and low efficacy of primary vaccinations in elderly people. The capacity to mount immune responses against new antigens is particularly affected in this population. However, its precise determinants are not fully understood. We aimed here at establishing the influence of persistent viral infections on the naive T-cell compartment and primary immune responsiveness in older adults. Methods: We assessed immunological parameters, related to CD8+ and CD4+ T-cell responsiveness, according to the serological status for common latent herpesviruses in two independent cohorts: 1) healthy individuals aged 19y to 95y (n = 150) and 2) individuals above 70y old enrolled in a primo-vaccination clinical trial (n = 137). Findings: We demonstrate a prevalent effect of age and CMV infection on CD8+ and CD4+ naive T cells, respectively. CMV seropositivity was associated with blunted CD4+ T-cell and antibody responses to primary vaccination. Interpretation: These data provide insights on the changes in adaptive immunity over time and the associated decline in vaccine efficacy with ageing. This knowledge is important for the management of emerging infectious diseases in elderly populations. more...
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- 2022
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5. Population Genomics of Francisella tularensis subsp. holarctica and its Implication on the Eco-Epidemiology of Tularemia in Switzerland
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Matthias Wittwer, Ekkehard Altpeter, Paola Pilo, Sebastian M. Gygli, Christian Beuret, Frederic Foucault, Rahel Ackermann-Gäumann, Urs Karrer, Daniela Jacob, Roland Grunow, and Nadia Schürch
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tularemia ,whole genome sequencing (WGS) ,ticks ,Francisella tularensis subsp. holarctica ,ecology ,epidemiology of infectious diseases ,Microbiology ,QR1-502 - Abstract
Whole genome sequencing (WGS) methods provide new possibilities in the field of molecular epidemiology. This is particularly true for monomorphic organisms where the discriminatory power of traditional methods (e.g., restriction enzyme length polymorphism typing, multi locus sequence typing etc.) is inadequate to elucidate complex disease transmission patterns, as well as resolving the phylogeny at high resolution on a micro-geographic scale. In this study, we present insights into the population structure of Francisella tularensis subsp. holarctica, the causative agent of tularemia in Switzerland. A total of 59 Fth isolates were obtained from castor bean ticks (Ixodes ricinus), animals and humans and a high resolution phylogeny was inferred using WGS methods. The majority of the Fth population in Switzerland belongs to the west European B.11 clade and shows an extraordinary genetic diversity underlining the old evolutionary history of the pathogen in the alpine region. Moreover, a new B.11 subclade was identified which was not described so far. The combined analysis of the epidemiological data of human tularemia cases with the whole genome sequences of the 59 isolates provide evidence that ticks play a pivotal role in transmitting Fth to humans and other vertebrates in Switzerland. This is further underlined by the correlation of disease risk estimates with climatic and ecological factors influencing the survival of ticks. more...
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- 2018
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6. Dissection of antibody specificities induced by yellow fever vaccination.
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Oksana Vratskikh, Karin Stiasny, Jürgen Zlatkovic, Georgios Tsouchnikas, Johanna Jarmer, Urs Karrer, Michael Roggendorf, Hedwig Roggendorf, Regina Allwinn, and Franz X Heinz
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
The live attenuated yellow fever (YF) vaccine has an excellent record of efficacy and one dose provides long-lasting immunity, which in many cases may last a lifetime. Vaccination stimulates strong innate and adaptive immune responses, and neutralizing antibodies are considered to be the major effectors that correlate with protection from disease. Similar to other flaviviruses, such antibodies are primarily induced by the viral envelope protein E, which consists of three distinct domains (DI, II, and III) and is presented at the surface of mature flavivirions in an icosahedral arrangement. In general, the dominance and individual variation of antibodies to different domains of viral surface proteins and their impact on neutralizing activity are aspects of humoral immunity that are not well understood. To gain insight into these phenomena, we established a platform of immunoassays using recombinant proteins and protein domains that allowed us to dissect and quantify fine specificities of the polyclonal antibody response after YF vaccination in a panel of 51 vaccinees as well as determine their contribution to virus neutralization by serum depletion analyses. Our data revealed a high degree of individual variation in antibody specificities present in post-vaccination sera and differences in the contribution of different antibody subsets to virus neutralization. Irrespective of individual variation, a substantial proportion of neutralizing activity appeared to be due to antibodies directed to complex quaternary epitopes displayed on the virion surface only but not on monomeric E. On the other hand, DIII-specific antibodies (presumed to have the highest neutralizing activity) as well as broadly flavivirus cross-reactive antibodies were absent or present at very low titers. These data provide new information on the fine specificity as well as variability of antibody responses after YF vaccination that are consistent with a strong influence of individual-specific factors on immunodominance in humoral immune responses. more...
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- 2013
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7. Immune senescence: relative contributions of age and cytomegalovirus infection.
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Andrea Mekker, Vincent S Tchang, Lea Haeberli, Annette Oxenius, Alexandra Trkola, and Urs Karrer
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Immunologic diseases. Allergy ,RC581-607 ,Biology (General) ,QH301-705.5 - Abstract
Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV) infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV) infection with or without thymectomy (Tx) alters antiviral immunity of young and aged mice. After infection with lymphocytic choriomeningitis virus (LCMV) or Vaccinia virus, specific antiviral T cell responses were significantly reduced in old, old MCMV-infected and/or Tx mice compared to young mice. Importantly, control of LCMV replication was more profoundly impaired in aged MCMV-infected mice compared to age-matched MCMV-naïve or young mice. In addition, latent MCMV infection was associated with slightly reduced vaccination efficacy in old Tx mice. In contrast to the prevailing hypothesis of a CMV-mediated restriction of the naïve T cell repertoire, we found similar naïve T cell numbers in MCMV-infected and non-infected mice, whereas ageing and Tx clearly reduced the naïve T cell pool. Instead, MCMV-infection expanded the total CD8(+) T cell pool by a massive accumulation of effector memory T cells. Based on these results, we propose a new model of increased competition between CMV-specific memory T cells and any 'de novo' immune response in aged individuals. In summary, our results directly demonstrate in a mouse model that latent CMV-infection impairs immunity in old age and propagates immune senescence. more...
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- 2012
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8. Tularemia in Children and Adolescents
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Urs Karrer, Chiara Imbimbo, Matthias Wittwer, and Michael Buettcher
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Microbiology (medical) ,Pediatrics ,medicine.medical_specialty ,Adolescent ,business.industry ,medicine.disease ,Anti-Bacterial Agents ,Tularemia ,Infectious Diseases ,Pediatrics, Perinatology and Child Health ,Humans ,Medicine ,Child ,business - Published
- 2020
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9. Mister Shulman: Ein Athlet verliert seine Flexibilität
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Miriam Hofmann, Corina Dommann-Scherrer, Urs Karrer, and Michael Streit
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General Medicine - Published
- 2022
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10. Wissenschaft und Politik in der Pandemie: eine Schweizer Perspektive
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Annette Oxenius and Urs Karrer
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- 2022
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11. Mononucléose infectieuse : mise à jour pour la pratique
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Katia Boggian, Urs Karrer, Klara M. Posfay-Barbe, Bernhard Wingeier, Peter Christiaan Carp, Martin Iff, Gisela Etter, Benedikt M. Huber, Joanna Sonderegger, Philip E. Tarr, Alexandra Calmy, and Thanh Doco Lecompte more...
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hemic and lymphatic diseases - Abstract
La mononucleose infectieuse aigue est un probleme frequent en medecine de ville. Dans 90% des cas, la mononucleose est due au virus Epstein-Barr (EBV) – pour de nombreux medecins, «EBV» et «mononucleose» sont synonymes. Le diagnostic n’est pas toujours facile, et certaines personnes atteintes ne presentent pas d’autres symptomes que la fatigue. more...
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- 2021
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12. Infektiöse Mononukleose: Update für die Praxis
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Benedikt M. Huber, Joanna Sonderegger, Thanh Doco Lecompte, Peter Christiaan Carp, Philip E. Tarr, Urs Karrer, Alexandra Calmy, Bernhard Wingeier, Gisela Etter, Klara M. Posfay-Barbe, Martin Iff, and Katia Boggian more...
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hemic and lymphatic diseases - Abstract
Die akute infektiose Mononukleose, oft auch Pfeiffersches Drusenfieber genannt, ist ein haufiges Problem in der Praxis. In 90% wird die Mononukleose durch das Epstein-Barr-Virus (EBV) verursacht – fur viele Arztinnen und Arzte sind «EBV» und «Pfeiffer» synonym. Die Diagnose ist nicht immer ganz einfach, zum Teil haben die Betroffenen ausser Mudigkeit wenig andere Symptome, und die Serologie ist nicht immer eindeutig. more...
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- 2021
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13. Multifactorial seroprofiling dissects the contribution of pre-existing human coronaviruses responses to SARS-CoV-2 immunity
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L. Maliqi, Alexander Wepf, Irene A Abela, Aline Wolfensberger, Peter Rusert, Maria C Hesselman, Dominique L Braun, Silvana K. Rampini, Eméry Schindler, Huldrych F. Günthard, Merle Schanz, Magdalena Schwarzmüller, Maddalena Marconato, Stefan Schmutz, Jochen Gottschalk, Michèle E Sickmann, Michael Huber, Alexandra Trkola, Selina Epp, Roger D. Kouyos, Urs Karrer, Patrick M. Meyer Sauteur, Annette Audigé, Chloé Pasin, Cyrille R Niklaus, Christoph Berger, Beat Frey, Jürg Böni, Jacqueline Weber, Annika Hunziker, Markus G. Manz, University of Zurich, Günthard, Huldrych F, and Kouyos, Roger D more...
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10028 Institute of Medical Virology ,viruses ,General Physics and Astronomy ,Antibodies, Viral ,medicine.disease_cause ,Neutralization ,Serology ,10234 Clinic for Infectious Diseases ,0302 clinical medicine ,Coronavirus 229E, Human ,skin and connective tissue diseases ,Coronavirus ,0303 health sciences ,Multidisciplinary ,virus diseases ,3100 General Physics and Astronomy ,3. Good health ,Vaccination ,Specific antibody ,Spike Glycoprotein, Coronavirus ,Protective immunity ,Science ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,610 Medicine & health ,1600 General Chemistry ,Genetics and Molecular Biology ,Context (language use) ,Biology ,Article ,Antibodies ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Disease severity ,1300 General Biochemistry, Genetics and Molecular Biology ,Immunity ,medicine ,Humans ,Seroconversion ,030304 developmental biology ,SARS-CoV-2 ,fungi ,COVID-19 ,Antimicrobial responses ,General Chemistry ,biochemical phenomena, metabolism, and nutrition ,Virology ,body regions ,Viral infection ,10036 Medical Clinic ,Immunoglobulin G ,10032 Clinic for Oncology and Hematology ,General Biochemistry ,Immunology ,10029 Clinic and Policlinic for Internal Medicine ,030217 neurology & neurosurgery - Abstract
Determination of SARS-CoV-2 antibody responses in the context of pre-existing immunity to circulating human coronavirus (HCoV) is critical for understanding protective immunity. Here we perform a multifactorial analysis of SARS-CoV-2 and HCoV antibody responses in pre-pandemic (N = 825) and SARS-CoV-2-infected donors (N = 389) using a custom-designed multiplex ABCORA assay. ABCORA seroprofiling, when combined with computational modeling, enables accurate definition of SARS-CoV-2 seroconversion and prediction of neutralization activity, and reveals intriguing interrelations with HCoV immunity. Specifically, higher HCoV antibody levels in SARS-CoV-2-negative donors suggest that pre-existing HCoV immunity may provide protection against SARS-CoV-2 acquisition. In those infected, higher HCoV activity is associated with elevated SARS-CoV-2 responses, indicating cross-stimulation. Most importantly, HCoV immunity may impact disease severity, as patients with high HCoV reactivity are less likely to require hospitalization. Collectively, our results suggest that HCoV immunity may promote rapid development of SARS-CoV-2-specific immunity, thereby underscoring the importance of exploring cross-protective responses for comprehensive coronavirus prevention., How the immune responses induced by SARS-CoV-2 and human coronavirus (hCoV) crosstalk is still unclear. Here the authors profile the humoral responses of prepandemic and SARS-CoV-2-infected donors to find that higher hCoV antibody titers are associated with SARS-CoV-2 negativity, and with reduced hospitalization in SARS-CoV-2 positive patients. more...
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- 2021
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14. Advanced multimodality MR imaging of a cerebral nocardiosis abscess in an immunocompetent patient with a focus on Amide Proton Transfer weighted imaging
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Elisabeth Sartoretti, Urs Karrer, Annina Gutzwiller, Sabine Sartoretti-Schefer, David Czell, Christoph A. Binkert, Simon Beyeler, Arash Najafi, and Thomas Sartoretti
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medicine.medical_specialty ,biology ,Focus (geometry) ,business.industry ,Cerebral Nocardiosis ,Amide proton ,Case Report ,General Medicine ,medicine.disease ,biology.organism_classification ,Ph changes ,Mr imaging ,medicine ,Radiology ,Abscess ,business ,Brain abscess ,Nocardia farcinica - Abstract
Cerebral nocardiosis abscess is a very rare entity in an immunocompetent patient. In this case report multiparametric and multimodality MR imaging characteristics of a pyogenic brain abscess caused by Nocardia Farcinica are discussed with a specific focus on amide proton transfer weighted imaging as a modern non-invasive, molecular MR imaging method which detects endogenous mobile protein and peptide concentration and tissue pH changes in pathologic brain lesions. The imaging characteristics are reviewed and discussed in respect to possible differential diagnoses, especially malignant tumorous lesions. more...
- Published
- 2020
15. Organizing a COVID-19 triage unit: a Swiss perspective
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Michael Streit, Tenzin Lamdark, Michel Adamina, Fabian Lunger, Nadine Molitor, Stefan Breitenstein, Ferda Gronki, Georgios Peros, Urs Karrer, Kiyoshi Sugimoto, University of Zurich, and Peros, Georgios more...
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0301 basic medicine ,Male ,Medical staff ,Epidemiology ,2405 Parasitology ,Review ,Drug Discovery ,Health care ,COVID ,3002 Drug Discovery ,2404 Microbiology ,General Medicine ,Tertiary care hospital ,Middle Aged ,Swiss ,Test (assessment) ,Hospitalization ,Infectious Diseases ,10209 Clinic for Cardiology ,Female ,Coronavirus Infections ,Switzerland ,Adult ,medicine.medical_specialty ,Coronavirus disease 2019 (COVID-19) ,Sars-CoV-2 ,030106 microbiology ,Immunology ,Pneumonia, Viral ,610 Medicine & health ,Microbiology ,Unit (housing) ,03 medical and health sciences ,Virology ,medicine ,Humans ,Pandemics ,2403 Immunology ,business.industry ,COVID-19 ,Mean age ,2725 Infectious Diseases ,Triage ,030104 developmental biology ,Emergency medicine ,2406 Virology ,Parasitology ,business ,2713 Epidemiology - Abstract
Background: With the rapid global spread of the acute respiratory syndrome coronavirus 2, urgent health-care measures have been implemented. We describe the organizational process in setting up a coronavirus disease 2019 triage unit in a Swiss tertiary care hospital. Methods: Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. Observations: A total of 1265 patients were screened between 10 March 2020 and 12 April 2020 at our Triage unit. Of these, 112 (8.9%) tested positive. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43.8 years (SD 16.3 years). Distinguishing between genders, mean age for females was 41.1 (SD 16.5) and mean age for males was 48.6 (SD 14.9), with females being significantly younger than males (p more...
- Published
- 2020
16. Organising a COVID-19 Triage Unit: A Swiss Perspective
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Urs Karrer, Stefan Breitenstein, Michel Adamina, Michael Streit, Ferda Gronki, Kiyoshi Sugimoto, Nadine Molitor, Tenzin Lamdark, Georgios Peros, and Fabian Lunger
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medicine.medical_specialty ,Patient safety ,Coronavirus disease 2019 (COVID-19) ,business.industry ,Pandemic ,Health care ,Emergency medicine ,Declaration ,medicine ,business ,Triage ,Unit (housing) ,Test (assessment) - Abstract
BACKGROUND: With the rapid global spread of the acute respiratory syndrome coronavirus 2 (SARS-CoV-2), urgent health-care measures have been implemented on both international and local levels. Here, we describe the organizational process in setting up a coronavirus disease 2019 (COVID-19) triage unit in a Swiss tertiary care hospital. METHODS: Our triage unit was set-up outside of the main hospital building and consists of three areas: 1. Pre-triage, 2. Triage, and 3. Triage plus. The Pre-triage check-points identify any potential COVID-19-infected patients and re-direct them to the main Triage area where trained medical staff screen which patients undergo diagnostic testing. If testing is indicated, nasopharyngeal swabs are performed. If patients require further investigations, they are referred to Triage plus. At this stage, patients are then discharged home after additional testing or admitted to the hospital for management. FINDINGS: A total of 1265 patients were screened between March 10th 2020 and April 12th 2020 at our Triage unit. Of these, 112 (8•9%) adults and 67 (5•3%) children tested positive for COVID-19. 73 (65%) of the positively-tested patients were female and 39 (35%) were male. The mean age for all patients was 43•8 years (SD 16.3 years). Distinguishing between genders, the mean age for females was 41•1 (SD 16•5) and the mean age for males was 48•6 (SD 14•9), with females being significantly younger than males (p more...
- Published
- 2020
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17. Disruption of coronin 1 signaling in T cells promotes allograft tolerance while maintaining anti-pathogen immunity
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Kerstin Siegmund, George Holländer, Beatrice Claudi, Nina Khanna, Michael Stiess, Simone Dertschnig, Eva Medina, Mathias Jakob Lang, Aleksandra Gumienny, Simona W. Rossi, Gabriele Kunz, Saumyabrata Mazumder, Vincent S. Tchang, Urs Karrer, Geoffrey Fucile, Jianping Li, Rajesh Jayachandran, Dirk Bumann, Jean Pieters, Mathias Schmaler, Beatrice Bolinger, Sebastian Ruehl, Despina Moshous, Anne-Kathrin Woischnig, and HZI,Helmholtz-Zentrum für Infektionsforschung GmbH, Inhoffenstr. 7,38124 Braunschweig, Germany. more...
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Graft Rejection ,0301 basic medicine ,Antigens, Fungal ,T-Lymphocytes ,Immunology ,Coronin ,Regulator ,chemical and pharmacologic phenomena ,Infections ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Immune system ,Antigen ,Immunity ,Cyclic AMP ,Animals ,Homeostasis ,Humans ,Immunology and Allergy ,Cyclic adenosine monophosphate ,Antigen-presenting cell ,Antigens, Viral ,Cells, Cultured ,Immunosuppression Therapy ,Mice, Knockout ,Antigens, Bacterial ,Mice, Inbred BALB C ,biology ,Graft Survival ,Microfilament Proteins ,Skin Transplantation ,Allografts ,Cell biology ,Mice, Inbred C57BL ,030104 developmental biology ,Infectious Diseases ,chemistry ,030220 oncology & carcinogenesis ,biology.protein ,Heart Transplantation ,Transplantation Tolerance ,Signal transduction ,Signal Transduction - Abstract
The ability of the immune system to discriminate self from non-self is essential for eradicating microbial pathogens but is also responsible for allograft rejection. Whether it is possible to selectively suppress alloresponses while maintaining anti-pathogen immunity remains unknown. We found that mice deficient in coronin 1, a regulator of naive T cell homeostasis, fully retained allografts while maintaining T cell-specific responses against microbial pathogens. Mechanistically, coronin 1-deficiency increased cyclic adenosine monophosphate (cAMP) concentrations to suppress allo-specific T cell responses. Costimulation induced on microbe-infected antigen presenting cells was able to overcome cAMP-mediated immunosuppression to maintain anti-pathogen immunity. In vivo pharmacological modulation of this pathway or a prior transfer of coronin 1-deficient T cells actively suppressed allograft rejection. These results define a coronin 1-dependent regulatory axis in T cells important for allograft rejection and suggest that modulation of this pathway may be a promising approach to achieve long-term acceptance of mismatched allografts. more...
- Published
- 2019
18. Tularämie – eine seltene Ursache der Pneumonie
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Urs Eriksson, Daniel Hofer, Ekkehardt Altpeter, René Fiechter, Urs Karrer, Nadia Schürch, Matthias Wittwer, and Simonne Rusterholz
- Abstract
Ein bisher selbstandiger 79-jahriger Patient wurde auf die Notfallstation zugewiesen bei seit drei Tagen bestehendem Fieber mit trockenem Husten sowie intermittierenden Abdominalschmerzen und Diarrhoe. more...
- Published
- 2018
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19. Close Geographic Association of Human Neoehrlichiosis and Tick Populations Carrying 'Candidatus Neoehrlichia mikurensis' in Eastern Switzerland
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Urs Karrer, Daniela Bircher, Guido V. Bloemberg, Peter M. Keller, Christian Beuret, Florian P. Maurer, Cornelia Joha, Jacques Gubler, Yvonne Achermann, Lukas Zimmerli, Jan Fehr, University of Zurich, and Bloemberg, Guido V more...
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Male ,Microbiology (medical) ,China ,Molecular Sequence Data ,610 Medicine & health ,Tick ,Polymerase Chain Reaction ,2726 Microbiology (medical) ,law.invention ,10234 Clinic for Infectious Diseases ,Ticks ,law ,RNA, Ribosomal, 16S ,Prevalence ,Animals ,Humans ,Multiplex ,Polymerase chain reaction ,Aged ,Genetics ,Base Sequence ,biology ,10179 Institute of Medical Microbiology ,Bacteriology ,Middle Aged ,Ribosomal RNA ,16S ribosomal RNA ,biology.organism_classification ,Virology ,Anaplasmataceae ,Europe ,Vector (epidemiology) ,Anaplasmataceae Infections ,570 Life sciences ,Female ,Topography, Medical ,Candidatus Neoehrlichia mikurensis ,10029 Clinic and Policlinic for Internal Medicine ,Sequence Alignment - Abstract
Neoehrlichiosis caused by “ Candidatus Neoehrlichia mikurensis” is an emerging zoonotic disease. In total, six patients have been described in Europe, with the first case detected in 2007. In addition, seven patients from China were described in a report published in October 2012. In 2009, we diagnosed the first human case of “ Ca . Neoehrlichia mikurensis” infection in the Zurich area (Switzerland). Here, we report two additional human cases from the same region, which were identified by broad-range 16S rRNA gene PCR. Both patients were immunocompromised and presented with similar clinical syndromes, including fever, malaise, and weight loss. A diagnostic multiplex real-time PCR was developed for specific detection of “ Ca . Neoehrlichia mikurensis” infections. The assay is based on the signature sequence of a 280-bp fragment of the “ Ca . Neoehrlichia mikurensis” 16S rRNA gene and incorporates a “ Ca . Neoehrlichia mikurensis” species, a “ Ca . Neoehrlichia” genus, and an Anaplasmataceae family probe for simultaneous screening. The analytical sensitivity was determined to be below five copies of the “ Ca . Neoehrlichia mikurensis” 16S rRNA gene. Our results show that the assay is suitable for the direct detection of “ Ca . Neoehrlichia mikurensis” DNA in clinical samples from, for example, blood and bone marrow. In addition, it allows for monitoring treatment response during antibiotic therapy. Using the same assay, DNA extracts from 1,916 ticks collected in four forests in close proximity to the patients' residences (Ca . Neoehrlichia mikurensis” was between 3.5 to 8% in pools of either nymphs, males, or females, showing a strong geographic association between the three patients and the assumed vector. more...
- Published
- 2013
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20. Diverging role for coronin 1 in antiviral CD4+ and CD8+ T cell responses
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Andrea Mekker, Jean Pieters, Vincent S. Tchang, Kerstin Siegmund, Urs Karrer, University of Zurich, and Tchang, Vincent Sam Yong
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CD4-Positive T-Lymphocytes ,Time Factors ,T cell ,viruses ,Immunology ,Coronin ,Fluorescent Antibody Technique ,610 Medicine & health ,CD8-Positive T-Lymphocytes ,Lymphocyte Activation ,Virus ,Vesicular stomatitis Indiana virus ,10234 Clinic for Infectious Diseases ,03 medical and health sciences ,Mice ,0302 clinical medicine ,RNA Virus Infections ,Lymphopenia ,medicine ,1312 Molecular Biology ,Cytotoxic T cell ,Animals ,Lymphocytic choriomeningitis virus ,Molecular Biology ,030304 developmental biology ,Mice, Knockout ,0303 health sciences ,2403 Immunology ,biology ,T-cell receptor ,Microfilament Proteins ,biology.organism_classification ,Flow Cytometry ,Survival Analysis ,3. Good health ,Cell biology ,Mice, Inbred C57BL ,Haematopoiesis ,medicine.anatomical_structure ,Vesicular stomatitis virus ,Host-Pathogen Interactions ,biology.protein ,CD8 ,030215 immunology - Abstract
Coronin 1 is a member of the evolutionary conserved WD repeat protein family and is highly expressed in hematopoietic cells. Coronin 1 is essential for Ca(2+) mobilization upon T cell receptor (TCR) stimulation providing a pro-survival signal for naive peripheral T cells. Both in mouse and in human, coronin 1 deficiency is associated with severe T cell lymphopenia. In this work, we have analyzed antiviral T cell-mediated immunity in the presence and absence of coronin 1 in vivo after infection with lymphocytic choriomenigitis virus (LCMV) and vesicular stomatitis virus (VSV) in mice. Despite low peripheral T cell numbers we found that LCMV-specific CD8(+) T cell responses were normal in the absence of coronin 1 and kinetics of LCMV-clearance were similar compared to wild type mice. In contrast, CD4(+) T cell responses were profoundly decreased after LCMV- and VSV-infection. We propose that coronin 1 plays a differential role in CD8(+) versus CD4(+) T cell responses and activation. more...
- Published
- 2013
21. Expansion of protective CD8+ T-cell responses driven by recombinant cytomegaloviruses
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Annette Oxenius, Urs Karrer, Paul Klenerman, Ulrich H. Koszinowski, Markus Wagner, Hartmut Hengel, Tilman Dumrese, Stefan Freigang, Sophie Sierro, and Rodney E. Phillips
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Muromegalovirus ,Cellular immunity ,viruses ,Immunology ,Cytomegalovirus ,Immunodominance ,CD8-Positive T-Lymphocytes ,Biology ,Lymphocytic choriomeningitis ,medicine.disease_cause ,Microbiology ,Virus ,Epitope ,Immediate-Early Proteins ,Mice ,Viral Proteins ,Orthomyxoviridae Infections ,Virology ,medicine ,Influenza A virus ,Animals ,Cytotoxic T cell ,Immunodominant Epitopes ,Herpesviridae Infections ,Orthomyxoviridae ,medicine.disease ,Mice, Inbred C57BL ,Insect Science ,Pathogenesis and Immunity ,CD8 - Abstract
CD8+T cells are critical for the control of many persistent viral infections, such as human immunodeficiency virus, hepatitis C virus, Epstein-Barr virus, and cytomegalovirus (CMV). In most infections, large CD8+-T-cell populations are induced early but then contract and are maintained thereafter at lower levels. In contrast, CD8+T cells specific for murine CMV (MCMV) have been shown to gradually accumulate after resolution of primary infection. This unique behavior is restricted to certain epitopes, including an immunodominant epitope derived from the immediate-early 1 (IE1) gene product. To explore the mechanism behind this further, we measured CD8+-T-cell-mediated immunity induced by recombinant MCMV-expressing epitopes derived from influenza A virus or lymphocytic choriomeningitis virus placed under the control of an IE promoter. We observed that virus-specific CD8+-T-cell populations were induced and that these expanded gradually over time. Importantly, these CD8+T cells provided long-term protection against challenge without boosting. These results demonstrate a unique pattern of accumulating T cells, which provide long-lasting immune protection, that is independent of the initial immunodominance of the epitope and indicates the potential of T-cell-inducing vaccines based on persistent vectors. more...
- Published
- 2016
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22. Cytomegalovirus and immune senescence: Culprit or innocent bystander?
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Andrea Mekker, Urs Karrer, Vincent S. Tchang, Kerstin Wanke, Lea Haeberli, University of Zurich, and Karrer, U
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Aging ,1303 Biochemistry ,Congenital cytomegalovirus infection ,610 Medicine & health ,CD8-Positive T-Lymphocytes ,Biology ,Biochemistry ,Culprit ,10234 Clinic for Infectious Diseases ,1307 Cell Biology ,1302 Aging ,Endocrinology ,Immune system ,1311 Genetics ,1312 Molecular Biology ,Genetics ,Bystander effect ,medicine ,Humans ,Molecular Biology ,Aged ,Aged, 80 and over ,Cell Biology ,medicine.disease ,Phenotype ,Pathophysiology ,1310 Endocrinology ,Ageing ,Cytomegalovirus Infections ,Immunology ,CD8 - Abstract
Immune senescence may be defined as the age-related reduction and dysregulation of immune function, and has been associated with increased incidence and severity of infectious diseases and with poor efficacy of prophylactic vaccines in the elderly. Several studies have demonstrated that persistent infections with Herpes viruses in general and Cytomegalovirus (CMV) in particular have a profound influence on subset distribution, phenotype and potentially also on the function of T cells in ageing individuals. The association of CMV-seropositivity and accumulation of CMV-specific CD8+ T cells with decreased survival in longitudinal studies of very elderly has fostered the hypothesis that CMV-infection may be an important causative factor for the development of immune senescence. Here, we have critically summarized the current body of evidence supporting this hypothesis, highlight some controversial issues about its relevance and mechanisms and propose areas of future research to demonstrate unequivocally whether and how persistent infections might compromise the ageing immune system. more...
- Published
- 2009
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23. Viral escape mechanisms - escapology taught by viruses
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Urs Karrer, Michaela Lucas, Paul Klenerman, and Andrew Lucas
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Arenavirus ,biology ,viruses ,virus diseases ,chemical and pharmacologic phenomena ,DNA virus ,Cell Biology ,biology.organism_classification ,Lymphocytic choriomeningitis ,medicine.disease ,Virology ,Virus ,Pathology and Forensic Medicine ,Immune system ,Betaherpesvirinae ,medicine ,Viral disease ,Molecular Biology ,Oncovirus - Abstract
Viruses have 'studied' immunology over millions of years of coevolution with their hosts. During this ongoing education they have developed countless mechanisms to escape from the host's immune system. To illustrate the most common strategies of viral immune escape we have focused on two murine models of persistent infection, lymphocytic choriomeningitis virus (LCMV) and murine cytomegalovirus (MCMV). LCMV is a fast replicating small RNA virus with a genome prone to mutations. Therefore, LCMV escapes from the immune system mainly by two strategies: 'speed' and 'shape change'. At the opposite extreme, MCMV is a large, complex DNA virus with a more rigid genome and thus the strategies used by LCMV are no option. However, MCMV has the coding capacity for additional genes which interfere specifically with the immune response of the host. These escape strategies have been described as 'camouflage' and 'sabotage'. Using these simple concepts we describe the spectrum of viral escapology, giving credit not only to the researchers who uncovered this fascinating area of immunology but also to the viruses themselves, who still have a few lessons to teach. more...
- Published
- 2008
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24. Emergence of Polyfunctional CD8+T Cells after Prolonged Suppression of Human Immunodeficiency Virus Replication by Antiretroviral Therapy
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Emma Gostick, Manuela Rehr, Annette Oxenius, Urs Karrer, Anna Haas, Julia Cahenzli, M Huber, David Price, University of Zurich, and Oxenius, A
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Adult ,Male ,Interleukin 2 ,RM ,1109 Insect Science ,Anti-HIV Agents ,Programmed Cell Death 1 Receptor ,Immunology ,HIV Infections ,610 Medicine & health ,CD8-Positive T-Lymphocytes ,Biology ,Microbiology ,Cohort Studies ,10234 Clinic for Infectious Diseases ,Interferon-gamma ,Interleukin 21 ,CD28 Antigens ,Antigen ,Antigens, CD ,Virology ,medicine ,Humans ,Cytotoxic T cell ,Interferon gamma ,2403 Immunology ,Receptors, Interleukin-7 ,Tumor Necrosis Factor-alpha ,2404 Microbiology ,CD28 ,Middle Aged ,Viral Load ,QR ,Insect Science ,HIV-1 ,2406 Virology ,Pathogenesis and Immunity ,Interleukin-2 ,Female ,Cytokine secretion ,Apoptosis Regulatory Proteins ,CD8 ,medicine.drug - Abstract
Progressive human immunodeficiency virus type 1 (HIV-1) infection is often associated with high plasma virus load (pVL) and impaired CD8+T-cell function; in contrast, CD8+T cells remain polyfunctional in long-term nonprogressors. However, it is still unclear whether CD8+T-cell dysfunction is the cause or the consequence of high pVLs. Here, we conducted a longitudinal functional and phenotypic analysis of virus-specific CD8+T cells in a cohort of patients with chronic HIV-1 infection. During the initiation and maintenance of successful antiretroviral therapy (ART), we assessed whether the level of pVL was associated with the degree of CD8+T-cell dysfunction. Under viremic conditions, HIV-specific CD8+T cells were dysfunctional with respect to cytokine secretion (gamma interferon, interleukin-2 [IL-2], and tumor necrosis factor alpha), and their phenotype suggested limited potential for proliferation. During ART, cytokine secretion by HIV-specific CD8+T cells was gradually restored, IL-7Rα and CD28 expression increased dramatically, and PD-1 levels declined. Thus, prolonged ART-induced reduction of viral replication and, hence, presumably antigen exposure in vivo, allows a significant functional restoration of CD8+T cells with the appearance of polyfunctional cells. These findings indicate that the level of pVL as a surrogate for antigen load has a dominant influence on the phenotypic and functional profile of virus-specific CD8+T cells. more...
- Published
- 2008
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25. CD4-guided scheduled treatment interruptions compared with continuous therapy for patients infected with HIV-1: results of the Staccato randomised trial
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Ploenchan Chetchotisakd, Reto Nüesch, Claudette S. Satchell, David A. Cooper, Warangkana Munsakul, Kiat Ruxrungtham, Michelle Le Braz, Enos Bernasconi, Daniel Genné, Jintanat Ananworanich, Phitsanu Raksakulkarn, Sabine Yerly, Praphan Phanuphak, Urs Karrer, Matthias Cavassini, Dominic Leduc, Sunee Sirivichayakul, Andrew Hill, Wisit Prasithsirikul, Angèle Gayet-Ageron, Bernard Hirschel, Hansjakob Furrer, Sasisopin Kiertiburanakul, Thomas V. Perneger, Somboon Tansuphasawasdikul, Luc Perrin, Pietro Vernazza, and Other departments more...
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Adult ,Male ,medicine.medical_specialty ,Numerical data ,Adolescent ,Endpoint Determination ,HIV Infections ,Staccato ,Drug Administration Schedule ,Acquired immunodeficiency syndrome (AIDS) ,Antiretroviral Therapy, Highly Active ,Internal medicine ,medicine ,Humans ,Sida ,Adverse effect ,Aged ,ddc:616 ,biology ,business.industry ,Hiv-1 ,General Medicine ,Drug holiday ,Middle Aged ,biology.organism_classification ,medicine.disease ,Surgery ,CD4 Lymphocyte Count ,Clinical trial ,HIV-1 ,HIV Infections/ drug therapy/immunology/transmission ,Female ,Viral disease ,business ,Viral load ,Antiretroviral Therapy, Highly Active/adverse effects/economics/ statistics & - Abstract
BACKGROUND: Stopping antiretroviral therapy in patients with HIV-1 infection can reduce costs and side-effects, but carries the risk of increased immune suppression and emergence of resistance. METHODS: 430 patients with CD4-positive T-lymphocyte (CD4) counts greater than 350 cells per muL, and viral load less than 50 copies per mL were randomised to continued therapy (n=146) or scheduled treatment interruptions (n=284). Median time on randomised treatment was 21.9 months (range 16.4-25.3). Primary endpoints were proportion of patients with viral load less than 50 copies per mL at the end of the trial, and amount of drugs used. Analysis was intention-to-treat. This study is registered at ClinicalTrials.gov with the identifier NCT00113126. FINDINGS: Drug savings in the scheduled treatment interruption group, compared with continuous treatment, amounted to 61.5%. 257 of 284 (90.5%) patients in the scheduled treatment interruption group reached a viral load less than 50 copies per mL, compared with 134 of 146 (91.8%) in the continued treatment group (difference 1.3%, 95% CI-4.3 to 6.9, p=0.90). No AIDS-defining events occurred. Diarrhoea and neuropathy were more frequent with continuous treatment; candidiasis was more frequent with scheduled treatment interruption. Ten patients (2.3%) had resistance mutations, with no significant differences between groups. INTERPRETATION: Drug savings with scheduled treatment interruption were substantial, and no evidence of increased treatment resistance emerged. Treatment-related adverse events were more frequent with continuous treatment, but low CD4 counts and minor manifestations of HIV infection were more frequent with scheduled treatment interruption. more...
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- 2006
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26. Die akute HIV-1-Infektion in Zürich: 2002–2004
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Leonardo Aceto, Urs Karrer, Huldrych F. Günthard, Alexandra Trkola, Herbert Kuster, Jürg Böni, Ch. Grube, Rainer Weber, Barbara Hasse, E. Presterl, R. Oberholzer, University of Zurich, and Günthard, H F more...
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10028 Institute of Medical Virology ,Pediatrics ,medicine.medical_specialty ,business.industry ,Transmission (medicine) ,610 Medicine & health ,2700 General Medicine ,General Medicine ,Drug resistance ,Interim analysis ,Rash ,Pharyngitis ,Acute Retroviral Syndrome ,medicine ,570 Life sciences ,biology ,medicine.symptom ,Prospective cohort study ,business ,HIV drug resistance - Abstract
Die akute HIV-1-Infektion manifestiert sich häufig als unspezifischer Symptomenkomplex und wird oft nicht als akutes retrovirales Syndrom erkannt. Wir präsentieren die Zwischenevaluation einer prospektiven Studie von 62 Patienten aus dem Grossraum Zürich mit dokumentierter akuter HIV-Infektion im Zeitraum zwischen Januar 2002 und August 2004. In 61.5% erfolgte die Übertragung über homosexuelle Kontakte, hauptsächlich mit dem HIV-1-Subtyp B, und in 34% fand eine Infektion über heterosexuelle Kontakte vorwiegend mit Non-B-Virus-Subtypen statt. Alle sexuell aktiven Altersklassen waren betroffen (18–72 Jahre). Klinisch prädominiertes Fieber (77%), Pharyngitis (56%), Malaise/Müdigkeit (52%), gastrointestinale Symptome (45%) und Exantheme (39%). Nur in 27% der Fälle wurde beim ersten Arztkontakt die richtige Verdachtsdiagnose gestellt. Die Patienten suchten primär ihren Hausarzt (37.5%) oder grössere Ambulatorien und Notfallstationen (37.5%) auf, und 16% wurden hospitalisiert. Bei 16% der Patienten wurden gleichzeitig weitere sexuell übertragbare Krankheiten diagnostiziert. Ein gegenüber antiretroviralen Medikamenten resistentes Virus war nur bei einem einzigen Patienten nachweisbar. more...
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- 2005
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27. Memory Inflation: Continuous Accumulation of Antiviral CD8+ T Cells Over Time
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Annette Oxenius, Paul Klenerman, Sophie Sierro, Urs Karrer, Rodney E. Phillips, Ulrich H. Koszinowski, Markus Wagner, and Hartmut Hengel
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Muromegalovirus ,T cell ,Immunology ,Epitopes, T-Lymphocyte ,Vaccinia virus ,CD8-Positive T-Lymphocytes ,Biology ,Lymphocyte Activation ,Virus Replication ,Epitope ,Immediate-Early Proteins ,Immunophenotyping ,Mice ,Interleukin 21 ,T-Lymphocyte Subsets ,Vaccinia ,medicine ,Animals ,Immunology and Allergy ,Cytotoxic T cell ,Lymphocyte Count ,Mice, Inbred BALB C ,Intracellular parasite ,T-cell receptor ,Herpesviridae Infections ,Molecular biology ,Clone Cells ,Virus Latency ,medicine.anatomical_structure ,Organ Specificity ,Female ,Immunologic Memory ,Memory T cell ,Cell Division ,CD8 - Abstract
CD8+ T lymphocytes play an important role in the control of intracellular pathogens during both acute and persistent infections. This is particularly true in the case of persistent herpesviruses such as human CMV, which are typified by large virus-specific CD8+ T cell populations during viral latency. To understand the origin of these populations and the factors shaping them over time, we investigated the CD8+ T cell response after murine CMV (MCMV) infection. The kinetics of the acute response were characterized by rapid expansion of activated T cells, followed by a contraction phase. Thereafter, we observed a striking pattern, where MCMV-specific memory CD8+ T cells steadily accumulated over time, with 20% of all CD8+ T cells at 1 year specific for one MCMV epitope. Accumulation of MCMV-specific CD8+ T lymphocytes was seen in all organs tested and was associated with continuous activation of specific CD8+ T lymphocytes, primarily within lymph nodes. The pattern of accumulation was observed in only two of five epitopes tested, and was accompanied by a gradual restriction in usage of the variable region of the TCR β-chain over time. This novel pattern of a virus-specific CD8+ T cell response suggests that continuous or repetitive exposure to Ag can slowly mold memory T cell populations over time. This may be relevant for understanding the evolution of the large human CMV-specific CD8+ T cell populations seen in humans. more...
- Published
- 2003
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28. Homonymous Hemianopsia in a Patient With Hodgkin's Lymphoma in Remission After BEACOPP Chemotherapy
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Cornelia Bruessow, Jacques Gubler, Miklos Pless, and Urs Karrer
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BEACOPP ,Cancer Research ,medicine.medical_specialty ,medicine.medical_treatment ,Homonymous hemianopsia ,Bleomycin ,Adrenal Cortex Hormones ,Antineoplastic Combined Chemotherapy Protocols ,Humans ,Medicine ,Cyclophosphamide ,Etoposide ,Neoplasm Staging ,Chemotherapy ,business.industry ,Biopsy, Needle ,Middle Aged ,Hodgkin's lymphoma ,medicine.disease ,Hodgkin Disease ,Immunohistochemistry ,Magnetic Resonance Imaging ,Oncology ,Doxorubicin ,Vincristine ,Procarbazine ,Disease Progression ,Hemianopsia ,Prednisone ,Female ,Radiology ,Neoplasm Recurrence, Local ,business ,Follow-Up Studies - Published
- 2012
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29. Marginal Zone Macrophages and Immune Responses Against Viruses
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Bernhard Odermatt, Stephan Oehen, Hans Hengartner, Urs Karrer, Constantino López-Macías, and Rolf M. Zinkernagel
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Immunology ,Spleen ,Lymphocytic Choriomeningitis ,Lymphocytic choriomeningitis ,Vesicular stomatitis Indiana virus ,Virus ,Mice ,Immune system ,medicine ,Animals ,Immunology and Allergy ,Innate immune system ,biology ,Macrophage Colony-Stimulating Factor ,Macrophages ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,Marginal zone ,Acquired immune system ,biology.organism_classification ,Virology ,Immunity, Innate ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Virus Diseases ,Vesicular stomatitis virus ,Disease Susceptibility ,T-Lymphocytes, Cytotoxic - Abstract
The effective establishment of antiviral protection requires a coordinated interplay between the innate and adaptive immune system. Using osteopetrotic (op−/−) mice, this study investigated the influence of marginal zone macrophages in controlling and initiating a protective immune response against a cytopathic vs a non- or low-cytopathic virus. Despite the generation of potent adaptive immune responses, antiviral protection against cytopathic vesicular stomatitis virus critically depended on the presence of marginal zone macrophages. Infection with low doses (100 PFU) of non- or low-cytopathic lymphocytic choriomeningitis virus was rarely cleared and usually resulted in a carrier state in the majority of mice. This shows that the early innate immune system provides an important preparatory phase to the adaptive immune system and is particularly important for antiviral protection. more...
- Published
- 2002
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30. Vertebral discitis after laparoscopic resection rectopexy: a rare differential diagnosis
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Stefan Breitenstein, Sarah-Noemi Knoll, Urs Karrer, and Pascal Probst
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medicine.medical_specialty ,medicine.diagnostic_test ,business.industry ,Lumbar vertebrae ,Case Reports ,medicine.disease ,Low back pain ,Surgery ,Rectal prolapse ,medicine.anatomical_structure ,medicine ,Discitis ,Back pain ,Vertebral osteomyelitis ,medicine.symptom ,Differential diagnosis ,Laparoscopy ,business - Abstract
Vertebral discitis usually arises from haematogenous spread of pathogens to the discs and bones. Vertebral discitis can rarely occur as a complication after laparoscopic operations with fixating sutures on the promontory. We report the case of an 81-year-old woman who underwent a laparoscopic resection rectopexy because of rectal prolapse. Weeks after the operation, the patient developed lower back pain with radiation to both legs not responding to symptomatic therapy. Two months later, a magnetic resonance imaging of the lumbar spine showed vertebral osteomyelitis and discitis. A fixation on the promontory may be sufficiently traumatic to the spine to pave the way for subsequent infection. A high index of suspicion should be raised in patients with persistent, severe back pain. Anamnesis, imageing and an adequate specimen from the affected area for microbiological analysis are crucial for timely diagnosis and appropriate management involving targeted and prolonged antimicrobial therapy. more...
- Published
- 2014
31. Epstein-Barr Virus und infektiöse Mononukleose
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Urs Karrer and David Nadal
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hemic and lymphatic diseases - Abstract
Die infektiose Mononukleose (IM) ist ein akutes klinisches Syndrom, charakterisiert durch Fieber, Tonsillo-Pharyngitis und bilaterale zervikale Lymphadenopathie. In 85–90% der Falle wird die IM durch eine Erstinfektion mit dem Epstein-Barr-Virus (EBV) verursacht. more...
- Published
- 2014
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32. Virus d’Epstein-Barr et mononucléose infectieuse
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David Nadal and Urs Karrer
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hemic and lymphatic diseases - Abstract
La mononucleose infectieuse (MI) est un syndrome clinique aigu caracterise par fievre, tonsillopharyngite et lymphadenopathie cervicale bilaterale. Dans 85–90% des cas la MI est provoquee par une primo-infection par le virus d’Epstein-Barr. more...
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- 2014
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33. Roles of tumour localization, second signals and cross priming in cytotoxic T-cell induction
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Jan Hermans, Marcus Pericin, Hans Hengartner, Rolf M. Zinkernagel, Bernhard Odermatt, Silvio Hemmi, Sophie Sierro, Adrian F. Ochsenbein, and Urs Karrer
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Lymphoid Tissue ,medicine.medical_treatment ,Antigen-Presenting Cells ,Priming (immunology) ,Biology ,Lymphocyte Activation ,Transfection ,Major histocompatibility complex ,Mice ,Immune system ,CD28 Antigens ,Antigen ,Antigens, Neoplasm ,Neoplasms ,Tumor Cells, Cultured ,medicine ,Animals ,Lymphocytic choriomeningitis virus ,Cytotoxic T cell ,Antigen-presenting cell ,Antigens, Viral ,Immunologic Surveillance ,Glycoproteins ,Multidisciplinary ,Histocompatibility Antigens Class I ,Immunotherapy ,Mice, Inbred C57BL ,CTL ,Lymphatic Metastasis ,Immunology ,B7-1 Antigen ,biology.protein ,Tumor Escape ,Lymph Nodes ,Neoplasm Transplantation ,Signal Transduction ,T-Lymphocytes, Cytotoxic - Abstract
The vertebrate immune system has evolved to protect against infections that threaten survival before reproduction. Clinically manifest tumours mostly arise after the reproductive years and somatic mutations allow even otherwise antigenic tumours to evade the attention of the immune system. Moreover, the lack of immunological co-stimulatory molecules on solid tumours could result in T-cell tolerance; that is, the failure of T cells to respond. However, this may not generally apply. Here we report several important findings regarding the immune response to tumours, on the basis of studies of several tumour types. First, tumour-specific induction of protective cytotoxic T cells (CTLs) depends on sufficient tumour cells reaching secondary lymphatic organs early and for a long enough duration. Second, diffusely invading systemic tumours delete CTLs. Third, tumours that stay strictly outside secondary lymphatic organs, or that are within these organs but separated from T cells by barriers, are ignored by T cells but do not delete them. Fourth, co-stimulatory molecules on tumour cells do not influence CTL priming but enhance primed CTL responses in peripheral solid tumours. Last, cross priming of CTLs by tumour antigens, mediated by major histocompatibility complex (MHC) class I molecules of antigen-presenting host cells, is inefficient and not protective. These rules of T-cell induction and maintenance not only change previous views but also rationales for anti-tumour immunotherapy. more...
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- 2001
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34. A comparison of T cell memory against the same antigen induced by virus versus intracellular bacteria
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J. L. Whitton, Rolf M. Zinkernagel, Jeff F. Miller, Paul Klenerman, Hao Shen, Adrian Ciurea, Adrian F. Ochsenbein, Alana Althage, Hans Hengartner, and Urs Karrer
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viruses ,T cell ,chemical and pharmacologic phenomena ,Lymphocytic Choriomeningitis ,Biology ,Lymphocytic choriomeningitis ,Epitope ,Epitopes ,Mice ,Antigen ,medicine ,Animals ,Lymphocytic choriomeningitis virus ,Cytotoxic T cell ,Antigens, Viral ,Antigens, Bacterial ,Mice, Inbred BALB C ,Vaccines, Synthetic ,Multidisciplinary ,virus diseases ,Viral Vaccines ,hemic and immune systems ,Biological Sciences ,medicine.disease ,Listeria monocytogenes ,Virology ,Recombinant Proteins ,nervous system diseases ,Bacterial vaccine ,CTL ,Nucleoproteins ,medicine.anatomical_structure ,Immunization ,Bacterial Vaccines ,Immunology ,Immunologic Memory ,T-Lymphocytes, Cytotoxic - Abstract
Cytotoxic T cell (CTL) memory was analyzed after infection with lymphocytic choriomeningitis virus (LCMV) and recombinantListeria monocytogenes(rLM) expressing the complete nucleoprotein of LCMV (rLM-NPactA) or only the immunodominant epitope of H-2dmice (rLM-NP118–126). Immunization with LCMV and rLM induced a long-lived increased CTL precursor (CTLp) frequency specific for the viral (NP118–126) and for the bacterial (LLO91–99) epitope, respectively. However, after infection with rLM memory, CTLs were less protective against an intravenous LCMV challenge infection than a comparable number of LCMV-induced memory T cells. LCMV, but not recombinantListeria-induced memory T cells were able to protect against lethal choriomeningitis by LCMV or a subsequent peripheral infection with recombinant vaccinia virus expressing LCMV-NP. The protective memory after viral and after rLM immunization was paralleled by evidence of LCMV but not rLM antigen persistence on day 15 and 30 after vaccination. These results document a striking difference in protective T cell memory between viral and bacterial vaccines and indicate that rapid T cell-dependent immune protection correlates with antigen persistence. more...
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- 1999
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35. On the Key Role of Secondary Lymphoid Organs in Antiviral Immune Responses Studied in Alymphoplastic (aly/aly) and Spleenless (Hox11−/−) Mutant Mice
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Charles W. M. Roberts, Shigeki Miyawaki, Urs Karrer, Stanley J. Korsmeyer, Hans Hengartner, Alana Althage, Rolf M. Zinkernagel, and Bernhard Odermatt
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Male ,Pore Forming Cytotoxic Proteins ,Adoptive cell transfer ,Lymphoid Tissue ,animal diseases ,Immunology ,Spleen ,Antibodies, Viral ,Lymphocytic choriomeningitis ,Article ,Virus ,Mice ,Immune system ,medicine ,Animals ,Immunology and Allergy ,Homeodomain Proteins ,Mice, Knockout ,Oncogene Proteins ,Membrane Glycoproteins ,biology ,Perforin ,Articles ,respiratory system ,medicine.disease ,biology.organism_classification ,Adoptive Transfer ,Immunohistochemistry ,Virology ,Mice, Mutant Strains ,respiratory tract diseases ,Mice, Inbred C57BL ,medicine.anatomical_structure ,Immunoglobulin M ,Virus Diseases ,Vesicular stomatitis virus ,biology.protein ,Female ,Antibody ,T-Lymphocytes, Cytotoxic - Abstract
The role of the spleen and of other organized secondary lymphoid organs for the induction of protective antiviral immune responses was evaluated in orphan homeobox gene 11 knockout mice (Hox11−/−) lacking the spleen, and in homozygous alymphoplastic mutant mice (aly/aly) possessing a structurally altered spleen but lacking lymph nodes and Peyer's patches. Absence of the spleen had no major effects on the immune response, other than delaying the antibody response by 1–2 d. In aly/aly mice, the thymus-independent IgM response against vesicular stomatitis virus (VSV) was delayed and reduced, whereas the T-dependent switch to the protective IgG was absent. Therefore, aly/aly mice were highly susceptible to VSV infection. Since aly/aly spleen cells yielded neutralizing IgM and IgG after adoptive transfer into recipients with normally structured secondary lymphoid organs, these data suggest that the structural defect was mainly responsible for inefficient T–B cooperation. Although aly/aly mice generated detectable, but reduced, CTL responses after infection with vaccinia virus (VV) and lymphocytic choriomeningitis virus (LCMV), the elimination of these viruses was either delayed (VV) or virtually impossible (LCMV); irrespective of the dose or the route of infection, aly/aly mice developed life-long LCMV persistence. These results document the critical role of organized secondary lymphoid organs in the induction of naive T and B cells. These structures also provide the basis for cooperative interactions between antigen-presenting cells, T cells, and B cells, which are a prerequisite for recovery from primary virus infections via skin or via blood. more...
- Published
- 1997
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36. Visiting friends and relatives (VFR): Ein unerwünschtes «Mitbringsel» von zu Hause
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Urs Karrer, Verena Schelling, and Jacques Gubler
- Abstract
Eine bisher gesunde 38-jahrige Somalierin, die seit sechs Jahren in der Schweiz lebt, suchte im Februar 2013 wegen seit zwei Wochen bestehendem Fieber, Kopf-, Gliederschmerzen und trockenem Husten die Notfallstation auf. Bis Mitte Dezember 2012 hatte sie sich fur zwei Monate in Nairobi (Kenia) aufgehalten. more...
- Published
- 2013
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37. Dissection of antibody specificities induced by yellow fever vaccination
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Regina Allwinn, Hedwig Roggendorf, Johanna Jarmer, Jürgen Zlatkovic, Oksana Vratskikh, Michael Roggendorf, Urs Karrer, Karin Stiasny, Georgios Tsouchnikas, Franz X. Heinz, and University of Zurich
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Medizin ,2405 Parasitology ,Antibodies, Viral ,Epitope ,10234 Clinic for Infectious Diseases ,Mice ,Cricetinae ,lcsh:QH301-705.5 ,0303 health sciences ,biology ,Vaccination ,Yellow Fever Vaccine ,2404 Microbiology ,3. Good health ,Medicine ,Antibody ,medicine.drug ,Research Article ,lcsh:Immunologic diseases. Allergy ,Immunology ,Yellow fever vaccine ,610 Medicine & health ,Immunodominance ,Cross Reactions ,Microbiology ,Cell Line ,03 medical and health sciences ,Immune system ,1311 Genetics ,Immunity ,Virology ,Yellow Fever ,Genetics ,medicine ,1312 Molecular Biology ,Animals ,Humans ,ddc:610 ,Molecular Biology ,Biology ,030304 developmental biology ,2403 Immunology ,030306 microbiology ,Antibodies, Neutralizing ,Immunity, Humoral ,lcsh:Biology (General) ,Polyclonal antibodies ,Humoral immunity ,Humoral Immunity ,biology.protein ,2406 Virology ,Parasitology ,Clinical Immunology ,lcsh:RC581-607 - Abstract
The live attenuated yellow fever (YF) vaccine has an excellent record of efficacy and one dose provides long-lasting immunity, which in many cases may last a lifetime. Vaccination stimulates strong innate and adaptive immune responses, and neutralizing antibodies are considered to be the major effectors that correlate with protection from disease. Similar to other flaviviruses, such antibodies are primarily induced by the viral envelope protein E, which consists of three distinct domains (DI, II, and III) and is presented at the surface of mature flavivirions in an icosahedral arrangement. In general, the dominance and individual variation of antibodies to different domains of viral surface proteins and their impact on neutralizing activity are aspects of humoral immunity that are not well understood. To gain insight into these phenomena, we established a platform of immunoassays using recombinant proteins and protein domains that allowed us to dissect and quantify fine specificities of the polyclonal antibody response after YF vaccination in a panel of 51 vaccinees as well as determine their contribution to virus neutralization by serum depletion analyses. Our data revealed a high degree of individual variation in antibody specificities present in post-vaccination sera and differences in the contribution of different antibody subsets to virus neutralization. Irrespective of individual variation, a substantial proportion of neutralizing activity appeared to be due to antibodies directed to complex quaternary epitopes displayed on the virion surface only but not on monomeric E. On the other hand, DIII-specific antibodies (presumed to have the highest neutralizing activity) as well as broadly flavivirus cross-reactive antibodies were absent or present at very low titers. These data provide new information on the fine specificity as well as variability of antibody responses after YF vaccination that are consistent with a strong influence of individual-specific factors on immunodominance in humoral immune responses., Author Summary The live-attenuated yellow fever vaccine has been administered to more than 600 million people worldwide and is considered to be one of the most successful viral vaccines ever produced. Following injection, the apathogenic vaccine virus replicates in the vaccinee and induces antibodies that mediate virus neutralization and subsequent protection from disease. In principle, many different antibodies are induced by viral antigens, but it is becoming increasingly clear that only a subset of them is capable of inactivating the virus, and some antibody populations appear to dominate the immune response. However, to date there has been very little information on individual-specific variations of immunodominance and how such variations can affect the functionality of antibody responses. In our study, we addressed these issues and analyzed the fine specificities of antibodies induced by YF vaccination as well as the contribution of different antibody subsets to virus neutralization in 51 vaccinees. We demonstrate an extensive degree of individual variation with respect to immunodominance of antibody populations and their contribution to virus neutralization. Such variations can have an impact on vaccine-mediated protection, and thus insight into this phenomenon can provide leads for novel strategies in modern vaccine design. more...
- Published
- 2013
38. Quantitative determination of IgM antibodies reduces the pitfalls in the serodiagnosis of tick-borne encephalitis
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Urs Karrer, Karin Stiasny, Heidemarie Holzmann, Vaclav Chmelik, Franz X. Heinz, Judith H. Aberle, University of Zurich, and Stiasny, K
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Adult ,Male ,Time Factors ,610 Medicine & health ,Dengue virus ,Antibodies, Viral ,medicine.disease_cause ,Encephalitis Viruses, Tick-Borne ,Dengue fever ,Cohort Studies ,10234 Clinic for Infectious Diseases ,Virology ,Humans ,Medicine ,False Positive Reactions ,Serologic Tests ,Flavivirus Infections ,biology ,business.industry ,Tick-borne encephalitis ,Infant ,2725 Infectious Diseases ,Middle Aged ,biology.organism_classification ,medicine.disease ,Flavivirus ,Tick-borne encephalitis virus ,Titer ,Infectious Diseases ,Immunoglobulin M ,Child, Preschool ,Immunoglobulin G ,Immunology ,2406 Virology ,Female ,business ,Encephalitis, Tick-Borne ,Encephalitis - Abstract
Background Tick-borne encephalitis (TBE) is the most important arbovirus disease in parts of Europe and Asia. Its laboratory diagnosis depends on the detection of specific IgM antibodies which can be impeded by (1) long-time persistence of IgM antibodies after infection, (2) vaccine-induced IgM antibodies, and (3) cross-reactive IgM antibodies from other flavivirus infections. Objectives To assess the extent of interference factors in the serodiagnosis of TBE that might lead to the false positive assignment of a recent infection. Study design We quantified TBE virus-specific IgM and IgG antibodies in sera collected at different time points from cohorts of (1) 61 TBE patients, (2) 131 TBE vaccinees, and (3) 42 patients with recent dengue or West Nile virus infections. Results All of the TBE patients were IgM- and IgG-positive upon hospitalization and 87% of acute TBE sera had IgM antibody titers of >500 Arbitrary Units (AU). These titers rapidly declined and only 16% of TBE patients had low IgM titers ≥9 months after infection. Vaccine-induced as well as flavivirus cross-reactive IgM antibodies were rarely detectable and of low titer. Conclusions Most of the potential problems of TBE serodiagnosis can be resolved by the quantification of IgM antibodies in a single serum sample taken upon hospitalization. High IgM values (>500 AU in our assay) are indicative of a recent infection. Lower IgM values, however, may require the analysis of a follow-up sample and/or a specific neutralization assay to exclude the possibilities of IgM persistence, vaccine-induced IgM antibodies or heterologous flavivirus infections. more...
- Published
- 2012
39. Cytomegalovirus Infection Impairs Immune Responses and Accentuates T-cell Pool Changes Observed in Mice with Aging
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Lea Haeberli, Urs Karrer, Andrea Mekker, Alexandra Trkola, Annette Oxenius, Vincent S. Tchang, University of Zurich, and Karrer, Urs
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10028 Institute of Medical Virology ,Cytomegalovirus Infection ,Viral Diseases ,Aging ,Muromegalovirus ,2405 Parasitology ,CD8-Positive T-Lymphocytes ,10234 Clinic for Infectious Diseases ,Mice ,0302 clinical medicine ,Vaccinia ,Lymphocytic choriomeningitis virus ,Cytotoxic T cell ,lcsh:QH301-705.5 ,0303 health sciences ,T Cells ,2404 Microbiology ,Aging and Immunity ,virus diseases ,Herpesviridae Infections ,Immunizations ,3. Good health ,Infectious Diseases ,medicine.anatomical_structure ,Medicine ,Research Article ,Senescence ,lcsh:Immunologic diseases. Allergy ,Naive T cell ,Immune Cells ,T cell ,Immunology ,610 Medicine & health ,Vaccinia virus ,Lymphocytic Choriomeningitis ,Biology ,Lymphocytic choriomeningitis ,Microbiology ,03 medical and health sciences ,Immune system ,1311 Genetics ,Immunity ,Virology ,1312 Molecular Biology ,Genetics ,medicine ,Animals ,Immunity to Infections ,Molecular Biology ,030304 developmental biology ,2403 Immunology ,Models, Immunological ,medicine.disease ,lcsh:Biology (General) ,2406 Virology ,570 Life sciences ,biology ,Parasitology ,lcsh:RC581-607 ,Immunologic Memory ,CD8 ,030215 immunology - Abstract
Immune senescence, defined as the age-associated dysregulation and dysfunction of the immune system, is characterised by impaired protective immunity and decreased efficacy of vaccines. Recent clinical, epidemiological and immunological studies suggest that Cytomegalovirus (CMV) infection may be associated with accelerated immune senescence, possibly by restricting the naïve T cell repertoire. However, direct evidence whether and how CMV-infection is implicated in immune senescence is still lacking. In this study, we have investigated whether latent mouse CMV (MCMV) infection with or without thymectomy (Tx) alters antiviral immunity of young and aged mice. After infection with lymphocytic choriomeningitis virus (LCMV) or Vaccinia virus, specific antiviral T cell responses were significantly reduced in old, old MCMV-infected and/or Tx mice compared to young mice. Importantly, control of LCMV replication was more profoundly impaired in aged MCMV-infected mice compared to age-matched MCMV-naïve or young mice. In addition, latent MCMV infection was associated with slightly reduced vaccination efficacy in old Tx mice. In contrast to the prevailing hypothesis of a CMV-mediated restriction of the naïve T cell repertoire, we found similar naïve T cell numbers in MCMV-infected and non-infected mice, whereas ageing and Tx clearly reduced the naïve T cell pool. Instead, MCMV-infection expanded the total CD8+ T cell pool by a massive accumulation of effector memory T cells. Based on these results, we propose a new model of increased competition between CMV-specific memory T cells and any ‘de novo’ immune response in aged individuals. In summary, our results directly demonstrate in a mouse model that latent CMV-infection impairs immunity in old age and propagates immune senescence., Author Summary Cytomegalovirus (CMV) persistently infects 50–90% of the human population. After primary infection, constant immune surveillance is required to prevent CMV-related disease. During ageing, increasing T cell resources are expended to keep CMV under control. Recent human studies have suggested that this investment may come at the cost of accelerated immune senescence, a condition describing the age-associated decline of the immune system's functionality. In the present study, we have developed a mouse model to directly investigate whether and how CMV-infection might impair immunity of aged individuals. We demonstrate that old mice with long-lasting CMV-infection are more susceptible to viral infections than old mice without CMV since their virus specific T cell response is suppressed. Contrary to the prevailing hypothesis we found no indication for a CMV-associated shrinking of the naïve T cell compartment. Instead, CMV-infection precipitated a massive expansion of memory T cells. Thus, we propose an alternative mechanism of CMV-enhanced immune senescence based on T cell competition between CMV-specific memory T cells and de novo generated T cell responses. In summary, we provide the first direct evidence that CMV-infection is indeed a propagating factor for poor immunity in the elderly. more...
- Published
- 2012
40. Hodgkin lymphoma in the Swiss HIV Cohort Study
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Gary M, Clifford, Martin, Rickenbach, Mauro, Lise, Luigino, Dal Maso, Manuel, Battegay, Julia, Bohlius, Emmanuelle, Boffi El Amari, Urs, Karrer, Gernot, Jundt, Andrea, Bordoni, Silvia, Ess, Silvia, Franceschi, S, Yerly, and University of Zurich more...
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Adult ,Male ,medicine.medical_specialty ,1303 Biochemistry ,Immunology ,2720 Hematology ,HIV Infections ,610 Medicine & health ,Biochemistry ,Cohort Studies ,10234 Clinic for Infectious Diseases ,1307 Cell Biology ,Acquired immunodeficiency syndrome (AIDS) ,Internal medicine ,Epidemiology ,medicine ,Humans ,Sida ,2403 Immunology ,biology ,business.industry ,Hazard ratio ,Cell Biology ,Hematology ,Odds ratio ,Middle Aged ,biology.organism_classification ,medicine.disease ,Hodgkin Disease ,Confidence interval ,Cohort ,Female ,business ,Biomarkers ,Switzerland ,Cohort study - Abstract
Hodgkin lymphoma (HL) risk is elevated among persons infected with HIV (PHIV) and has been suggested to have increased in the era of combined antiretroviral therapy (cART). Among 14 606 PHIV followed more than 20 years in the Swiss HIV Cohort Study (SHCS), determinants of HL were investigated using 2 different approaches, namely, a cohort and nested case-control study, estimating hazard ratios (HRs) and matched odds ratios, respectively. Forty-seven incident HL cases occurred during 84 611 person-years of SHCS follow-up. HL risk was significantly higher among men having sex with men (HR vs intravenous drug users = 2.44, 95% confidence interval [CI], 1.13-5.24) but did not vary by calendar period (HR for 2002-2007 vs 1995 or earlier = 0.65, 95% CI, 0.29-1.44) or cART use (HR vs nonusers = 1.02, 95% CI, 0.53-1.94). HL risk tended to increase with declining CD4+ cell counts, but these differences were not significant. A lower CD4+/CD8+ ratio at SHCS enrollment or 1 to 2 years before HL diagnosis, however, was significantly associated with increased HL risk. In conclusion, HL risk does not appear to be increasing in recent years or among PHIV using cART in Switzerland, and there was no evidence that HL risk should be increased in the setting of improved immunity. more...
- Published
- 2009
41. Infektionskrankheiten im Alter
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Urs Karrer and Karl-Heinz Krause
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business.industry ,Medicine ,business - Published
- 2008
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42. Autorinnen und Autoren
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Manuel Battegay, Torsten T. Bauer, Stephan Becker, Karsten Becker, Michael Bolz, Wolfgang Bredt, Markus W. Büchler, Gerd-Dieter Burchard, Gregor Caspari, Markus Cornberg, Thomas Dobner, Hans W. Doerr, Eugen Domann, Christian Drosten, Christof von Eiff, Hermann Einsele, Andreas Essig, Wolfgang Fegeler, Jan Fehr, Klaus Friese, Barbara C. Gärtner, Petra Gastmeier, Sören G. Gatermann, Florian Gebhard, Christine Geffers, Wolfram H. Gerlich, Bernhard Glasbrenner, Thomas Glück, Uwe Groß, Martin Groschup, Gerhard Haase, Hans-Jochen Hagedorn, Holger Hebart, Jürgen Heesemann, Werner J. Heinz, Peter Helbling, Hartmut Hengel, Mathias Herrmann, Henning Heumann, Hans H. Hirsch, Gert Höffken, Achim Hörauf, Peter Itin, Wolfgang Jilg, Reinhard Kandolf, Urs Karrer, Stefan H.E. Kaufmann, Peter Kern, Winfried V. Kern, Manfred Kist, Hanns-Peter Knaebel, Klaus Korn, Karl-Heinz Krause, Thomas Krieg, Joachim Kühn, Gerd Laifer, Gerhard K. Lang, Jan Leidel, Oliver Liesenfeld, Thomas Löscher, Albert C. Ludolph, Daniela Männel, Michael P. Manns, Reinhard Marre, Franz-Rainer Matuschka, Thomas Mertens, Thomas Mettenleiter, Detlef Michel, Joachim Morschhäuser, Lutz von Müller, Ioannis Mylonas, Kurt G. Naber, Dieter Neumann-Haefelin, Michael Nevels, Reto Nüesch, Markus Otto, Georg Pauli, Matthias Pauschinger, Georg Peters, Herbert Pfister, Gabriela Pfyffer von Altishofen, Bodo Plachter, Andreas Podbielski, Therese Popow-Kraupp, Ulrike Protzer, Matthias J. Reddehase, Axel Rethwilm, Andreas Ritzkowsky, Andreas Roggenkamp, Christoph Rudin, Henning Rüden, Carsten Schwarz, Christoph M. Seiler, Parham Sendi, Joachim Sieper, Anja Sigge, Barbara Spellerberg, Peter Staib, Michael Steuerwald, Reinhild Strauss, Cord Henrich Sunderkötter, Jan ter Meulen, Matthias Trautmann, Burkhard Tümmler, Hayrettin Tumani, Ernst Vanek †, Johannes Veit, Pietro Vernazza, Florian Wagenlehner, Wolfgang Weidner, Thomas Weinke, Hartmut Weißbrodt, Jens Werner, Bettina Wilske, Carl H. Wirsing von König, and Werner Zimmerli more...
- Published
- 2008
- Full Text
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43. Treatment and prognosis of AIDS-related lymphoma in the era of highly active antiretroviral therapy: findings from the Swiss HIV Cohort Study
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Enos Bernasconi, Michael T. Koller, Miklos Pless, Martin Rickenbach, Pedram Sendi, Heiner C. Bucher, Urs Karrer, Barbara Bertisch, Pietro Vernazza, Sophie Moirandat-Rytz, Manuel Battegay, Monika Blasko, Samir Vora, Benedetta Terziroli, James Owen Robinson, Bernard Hirschel, Mathew Simcock, Hansjakob Furrer, and Liisa Blumer more...
- Subjects
Adult ,Male ,medicine.medical_specialty ,Dosage/ therapeutic use ,Anti-HIV Agents/ therapeutic use ,Anti-HIV Agents ,Antineoplastic Agents ,HIV Infections ,Kaplan-Meier Estimate ,AIDS-related lymphoma ,Lymphoma, AIDS-Related/complications/ drug therapy/mortality ,Cohort Studies ,International Prognostic Index ,immune system diseases ,Median follow-up ,Hepatitis C/complications ,Internal medicine ,Antiretroviral Therapy, Highly Active ,Antineoplastic Combined Chemotherapy Protocols ,Antineoplastic Agents/ therapeutic use ,medicine ,Humans ,Pharmacology (medical) ,Prospective Studies ,Kaplan-Meiers Estimate ,Lymphoma, AIDS-Related ,ddc:616 ,Pharmacology ,business.industry ,Proportional hazards model ,Hazard ratio ,Hepatitis C ,Middle Aged ,medicine.disease ,Prognosis ,HIV Infections/complications/ drug therapy/mortality/virology ,Lymphoma ,Surgery ,CD4 Lymphocyte Count ,Antineoplastic Combined Chemotherapy Protocols/administration & ,Infectious Diseases ,Female ,business ,Cohort study - Abstract
Objective To assess the characteristics of combination antiretroviral therapy (cART) administered concomitantly with chemotherapy and to establish prognostic determinants of patients with AIDS-related non-Hodgkin's lymphoma. Methods The study included 91 patients with AIDS-related non-Hodgkin's lymphoma from the Swiss HIV Cohort Study enrolled between January 1997 and October 2003, excluding lymphomas of the brain. We extracted AIDS-related non-Hodgkin's lymphoma- and HIV-specific variables at the time of lymphoma diagnosis as well as treatment changes over time from charts and from the Swiss HIV Cohort Study database. Cox regression analyses were performed to study predictors of overall and progression-free survival. Results During a median follow up of 1.6 years, 57 patients died or progressed. Thirty-five patients stopped chemotherapy prematurely (before the sixth cycle) usually due to disease progression; these patients had a shorter median survival than those who completed six or more cycles (14 versus 28 months). Interruptions of cART decreased from 35% before chemotherapy to 5% during chemotherapy. Factors associated with overall survival were CD4+ T-cell count (Conclusions Interruptions of cART were usually not induced by chemotherapy. The effect of cART interruptions on AIDS-related non-Hodgkin's lymphoma prognosis remains unclear, however, hepatitis C seropositivity emerged as a predictor of death beyond the well-known international prognostic index score and CD4+ T-cell count. more...
- Published
- 2007
44. Impaired NFAT nuclear translocation results in split exhaustion of virus-specific CD8+ T cell functions during chronic viral infection
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Annette Oxenius, Urs Karrer, Manuela Rehr, Petra Wolint, Julia Cahenzli, and Paola Agnellini
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Active Transport, Cell Nucleus ,HIV Infections ,Cell Separation ,Biology ,CD8-Positive T-Lymphocytes ,Lymphocytic choriomeningitis ,Virus ,Mice ,Immune system ,Antigen ,medicine ,Cytotoxic T cell ,Animals ,Transgenes ,Multidisciplinary ,NFATC Transcription Factors ,HIV ,NFAT ,Biological Sciences ,medicine.disease ,Flow Cytometry ,Mice, Inbred C57BL ,Perfusion ,Chronic infection ,Immune System ,Immunology ,Cytokines ,Calcium ,CD8 - Abstract
In persistent viral infections, the host's immune system is challenged by the constant exposure to antigen, potentially causing continuous activation of CD8 + T cells with subsequent immunopathology. Here we demonstrate, for experimental chronic lymphocytic choriomeningitis virus and human HIV infection, that upon prolonged in vivo exposure to antigen, TCR-triggered Ca 2+ flux, degranulation, and cytotoxicity are maintained on a cellular level, whereas cytokine production is severely impaired because of a selective defect in activation-induced NFAT nuclear translocation. During chronic infection, this differential regulation of pathways leading to diverse effector functions may allow CD8 + T cells to sustain some degree of local viral control by direct cytotoxicity while limiting systemic immune pathology by silencing cytokine production. more...
- Published
- 2007
45. Dose-dependent influence of didanosine on immune recovery in HIV-infected patients treated with tenofovir
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Bruno Ledergerber, Marina Russotti, Roberto F. Speck, Patrick Schmid, Matthias Cavassini, Rainer Weber, Angèle Gayet-Ageron, Bernard Hirschel, Hansjakob Furrer, Urs Karrer, Manuel Battegay, and Luigia Elzi more...
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Male ,medicine.medical_treatment ,HIV Infections ,Gastroenterology ,immune system diseases ,Immunopathology ,Immunology and Allergy ,Sida ,Didanosine ,ddc:616 ,Reverse-transcriptase inhibitor ,biology ,virus diseases ,Reverse Transcriptase Inhibitors/ administration & dosage/immunology ,Middle Aged ,Infectious Diseases ,Treatment Outcome ,Toxicity ,RNA, Viral ,Reverse Transcriptase Inhibitors ,Drug Therapy, Combination ,Female ,medicine.drug ,Adult ,medicine.medical_specialty ,Immunology ,Adenine/administration & dosage/ analogs & derivatives/immunology ,Organophosphonates ,Dose-Response Relationship, Immunologic ,Drug Administration Schedule ,Phosphonic Acids/ administration & dosage/immunology ,Internal medicine ,parasitic diseases ,medicine ,Humans ,Tenofovir ,Retrospective Studies ,Chemotherapy ,HIV Infections/ drug therapy/immunology ,Adenine ,Didanosine/ administration & dosage/immunology ,Drug interaction ,biochemical phenomena, metabolism, and nutrition ,biology.organism_classification ,CD4 Lymphocyte Count ,Regimen ,RNA, Viral/analysis - Abstract
BACKGROUND: Antiretroviral therapy (ART) containing tenofovir disoproxil fumarate (TDF) and didanosine (ddI) has been associated with poor immune recovery despite virologic success. This effect might be related to ddI toxicity since ddI exposure is substantially increased by TDF. OBJECTIVE: To analyze whether immune recovery during ART with TDF and ddI is ddI-dose dependent. DESIGN AND METHODS: A retrospective longitudinal analysis of immune recovery measured by the CD4 T-cell slope in 614 patients treated with ART containing TDF with or without ddI. Patients were stratified according to the tertiles of their weight-adjusted ddI dose: low dose (< 3.3 mg/kg), intermediate dose (3.3-4.1 mg/kg) and high dose (> 4.1 mg/kg). Cofactors modifying the degree of immune recovery after starting TDF-containing ART were identified by univariable and multivariable linear regression analyses. RESULTS: CD4 T-cell slopes were comparable between patients treated with TDF and a weight-adjusted ddI-dose of < 4.1 mg/kg per day (n = 143) versus TDF-without-ddI (n = 393). In the multivariable model the slopes differed by -13 CD4 T cells/mul per year [95% confidence interval (CI), -42 to 17; P = 0.40]. In contrast, patients treated with TDF and a higher ddI dose (> 4.1 mg/kg per day, n = 78) experienced a significantly impaired immune recovery (-47 CD4 T cells/microl per year; 95% CI, -82 to -12; P = 0.009). The virologic response was comparable between the different treatment groups. CONCLUSIONS: Immune recovery is impaired, when high doses of ddI (> 4.1 mg/kg) are given in combination with TDF. If the dose of ddI is adjusted to less than 4.1 mg/kg per day, immune recovery is similar to other TDF-containing ART regimen. more...
- Published
- 2005
46. Fatal Cytomegalovirus Pneumonitis and Ileitis in a Patient with a Cardiac Assist Device
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Urs Karrer, Tanja Reineke, Markus J. Wilhelm, Benedikt Huttner, University of Zurich, and Huttner, B
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Cardiomyopathy, Dilated ,Male ,medicine.medical_specialty ,Prosthesis-Related Infections ,Time Factors ,Congenital cytomegalovirus infection ,Cytomegalovirus ,610 Medicine & health ,Polymerase Chain Reaction ,Gastroenterology ,Diagnosis, Differential ,Viral Matrix Proteins ,Fatal Outcome ,Internal medicine ,medicine ,Humans ,Ileitis ,Cardiac assist ,Antigens, Viral ,Pneumonitis ,business.industry ,Pneumonia ,General Medicine ,Middle Aged ,Phosphoproteins ,medicine.disease ,10020 Clinic for Cardiac Surgery ,2746 Surgery ,Cytomegalovirus Infections ,DNA, Viral ,Heart-Assist Devices ,business ,Follow-Up Studies - Published
- 2011
- Full Text
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47. Memory T cells: total recall or just a sense of deja vu?
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Annette Oxenius, Rodney E. Phillips, Paul Klenerman, and Urs Karrer
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Recall ,viruses ,Immunology ,Biology ,Lymphocytic choriomeningitis ,medicine.disease ,Virology ,Epitope ,Virus ,chemistry.chemical_compound ,chemistry ,Déjà vu ,Sense (molecular biology) ,medicine ,Immunology and Allergy ,Interferon gamma ,Vaccinia ,medicine.drug - Abstract
Is a lifetime of sequential viral infections detrimental or advantageous to the host? New evidence suggests that pre-existing memory T cells specific for one type of virus can alter, for the better, the disease outcome after infection with an unrelated virus. more...
- Published
- 2001
48. Immunodeficiency of alymphoplasia mice (aly/aly) in vivo: structural defect of secondary lymphoid organs and functional B cell defect
- Author
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Bernhart Odermatt, Alana Althage, Urs Karrer, Rolf M. Zinkernagel, and Hans Hengartner
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Cytotoxicity, Immunologic ,Male ,Lymphoid Tissue ,animal diseases ,T cell ,Immunology ,Spleen ,Lymphocytic Choriomeningitis ,Antibodies, Viral ,Vesicular stomatitis Indiana virus ,Mice ,Immune system ,Agammaglobulinemia ,Lymphopenia ,medicine ,Immunology and Allergy ,Cytotoxic T cell ,Animals ,Lymphocytic choriomeningitis virus ,Encephalitis, Viral ,Viremia ,CD40 Antigens ,B cell ,Bone Marrow Transplantation ,Mice, Knockout ,B-Lymphocytes ,CD40 ,biology ,Immunologic Deficiency Syndromes ,respiratory system ,Viral Load ,Virology ,Molecular biology ,respiratory tract diseases ,Specific Pathogen-Free Organisms ,Mice, Inbred C57BL ,CTL ,medicine.anatomical_structure ,Immunoglobulin M ,Liver ,Mice, Inbred DBA ,Immunoglobulin G ,Radiation Chimera ,biology.protein ,Female ,Lymphotoxin beta receptor - Abstract
Alymphoplasia mice (aly/aly) have been shown to be deficient for a nuclear factor-kappaB-inducing kinase involved in signal transduction of lymphotoxin beta receptor (LT-betaR) and of CD40, resulting in structural defects of secondary lymphoid organs and highly increased susceptibility to viral infections. We analyzed the anti-viral immune response of bone marrow chimeras (BMC) between aly/aly mice and (C57BL/6 x DBA2)F1 mice (B6D2F1) to evaluate in vivo whether the structural defects of secondary lymphoid organs or intrinsic B or T cell defects led to immunodeficiency in aly/aly mice. Transfer of aly/aly bone marrow into B6D2F1 mice (aly/aly-->B6D2F1) led to excellent T but poor B cell reconstitution of recipients. Antiviral cytotoxic T cell (CTL) responses of aly/aly-->B6D2F1 BMC were clearly improved compared to aly/aly mice whereas virus-neutralizing IgG reponses were virtually absent. Therefore, the inefficient CTL response was predominantly caused by the structural defect of secondary lymphoid organs and not by an intrinsic T cell defect. In contrast, B cells of aly/aly origin were unable to undergo isotype switch after viral infections, indicating an intrinsic B cell defect in vivo. Overall, aly/aly mice show the combined immunodeficient phenotype of mice deficient for LT-3R with B cells functionally deficient for CD40. more...
- Published
- 2000
49. Immune surveillance against a solid tumor fails because of immunological ignorance
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Urs Karrer, Hans Hengartner, Paul Klenerman, Marcus Pericin, Rolf M. Zinkernagel, Adrian F. Ochsenbein, and Burkhard Ludewig
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Fibrosarcoma ,T-Lymphocytes ,medicine.medical_treatment ,Antigen presentation ,Mice, Nude ,Bone Marrow Cells ,Mice, Transgenic ,Biology ,Lymphocyte Depletion ,Mice ,Interleukin 21 ,Antigen ,Antigens, Neoplasm ,medicine ,Animals ,Cytotoxic T cell ,Antigen-presenting cell ,Antigens, Viral ,Immunologic Surveillance ,Clonal Anergy ,Homeodomain Proteins ,Mice, Knockout ,Multidisciplinary ,Clonal anergy ,Immunologic Deficiency Syndromes ,Dendritic Cells ,Immunotherapy ,Biological Sciences ,Tumor antigen ,Mice, Inbred C57BL ,Immunology ,T-Lymphocytes, Cytotoxic - Abstract
Many peripheral solid tumors such as sarcomas and carcinomas express tumor-specific antigens that can serve as targets for immune effector T cells. Nevertheless, overall immune surveillance against such tumors seems relatively inefficient. We studied immune surveillance against a s.c. sarcoma expressing a characterized viral tumor antigen. Surprisingly, the tumor cells were capable of inducing a protective cytotoxic T cell response if transferred as a single-cell suspension. However, if they were transplanted as small tumor pieces, tumors readily grew. Tumor growth correlated strictly with (i) failure of tumor cells to reach the draining lymph nodes and (ii) absence of primed cytotoxic T cells. Cytotoxic T cells were not tolerant or deleted because a tumor antigen-specific cytotoxic T cell response was readily induced in lymphoid tissue by immunization with virus or with tumor cells even in the presence of large tumors. Established tumors were rejected by vaccine-induced effector T cells if effector T cells were maintained by prolonged or repetitive vaccination, but not by single-dose vaccination. Thus, in addition to several other tumor-promoting parameters, some antigenic peripheral sarcomas—and probably carcinomas—may grow not because they anergize or tolerize tumor-specific T cells, but because such tumors are immunologically dealt with as if they were in a so-called immunologically privileged site and are ignored for too long. more...
- Published
- 1999
50. IL-12 is not required for induction of type 1 cytokine responses in viral infections
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Annette Oxenius, Urs Karrer, Rolf M. Zinkernagel, and Hans Hengartner
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CD4-Positive T-Lymphocytes ,Mice, Knockout ,Immunology ,Lymphocytic Choriomeningitis ,Th1 Cells ,Antibodies, Viral ,Lymphocyte Activation ,Virus Replication ,Interleukin-12 ,Vesicular stomatitis Indiana virus ,Killer Cells, Natural ,Mice, Inbred C57BL ,Mice ,Immunoglobulin G ,Immunology and Allergy ,Animals ,Cytokines ,Lymphocytic choriomeningitis virus ,Listeriosis - Abstract
To investigate the physiological role of IL-12 in viral infections in terms of T cell cytokine responses involved in virus-specific Ig isotype induction and in antiviral protection, immune responses elicited upon infection of IL-12-deficient mice with lymphocytic choriomeningitis virus (LCMV) or vesicular stomatitis virus (VSV) were studied. Infection of IL-12-deficient mice with LCMV induced a virus-specific type 1 cytokine response as determined by in vitro cytokine secretion patterns as well as by in vivo intracellular cytokine staining of LCMV-specific CD4+ TCR transgenic T cells that had clonally expanded in LCMV-infected IL-12-deficient recipient mice. In addition, LCMV- and VSV-specific IgG responses exhibited normal serum IgG2a/IgG1 ratios, demonstrating again virus-specific CD4+ T cell induction of type 1 phenotype in IL-12-deficient mice upon viral infection. LCMV and VSV immune mice were found to be protected against challenge immunization with recombinant vaccinia viruses expressing either the LCMV- or the VSV-derived glycoprotein, respectively. This protection is known to be mediated by T cell-secreted type 1 cytokines IFN-γ and TNF-α. In contrast, IL-12-deficient mice showed impaired abilities to control infection with the facultative intracellular bacterium Listeria monocytogenes at early time points after infection. However, at later time points of infection, IL-12-deficient mice were able to clear infection. These findings may indicate that viruses are able to induce type 1 T cell responses in the absence of IL-12 as opposed to some bacterial or parasitical infections that are crucially dependent on the presence of IL-12 for the induction of type 1 immune responses. more...
- Published
- 1999
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