23 research outputs found
Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques
No full textPrevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1–specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3. On days 1, 4, 7 and 10 after virus exposure, we injected animals subcutaneously with NmAbs and quantified systemic distribution of NmAbs in multiple tissues within 24 h after antibody administration. Replicating virus was found in multiple tissues by day 1 in animals that were not treated. All NmAb-treated macaques were free of virus in blood and tissues at 6 months after exposure. We detected no anti-SHIV T cell responses in blood or tissues at necropsy, and no virus emerged after CD8+ T cell depletion. These results suggest that early passive immunotherapy can eliminate early viral foci and thereby prevent the establishment of viral reservoirs.Fil: Hessell, Ann J.. Oregon Health and Science University; Estados UnidosFil: Jaworski, Juan Pablo. Oregon Health and Science University; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Epson, Erin. Oregon Health and Science University; Estados UnidosFil: Matsuda, Kenta. National Institutes of Health; Estados UnidosFil: Pandey, Shilpi. Oregon Health and Science University; Estados UnidosFil: Kahl, Christoph. Oregon Health and Science University; Estados UnidosFil: Reed, Jason. Oregon Health and Science University; Estados UnidosFil: Sutton, William F.. Oregon Health and Science University; Estados UnidosFil: Hammond, Katherine B.. Oregon Health and Science University; Estados UnidosFil: Cheever, Tracy A.. Oregon Health and Science University; Estados UnidosFil: Barnette, Philip T.. Oregon Health and Science University; Estados UnidosFil: Legasse, Alfred W.. Oregon Health and Science University; Estados UnidosFil: Planer, Shannon. Oregon Health and Science University; Estados UnidosFil: Stanton, Jeffrey J.. Oregon Health and Science University; Estados UnidosFil: Pegu, Amarendra. National Institutes of Health; Estados UnidosFil: Chen, Xuejun. National Institutes of Health; Estados UnidosFil: Wang, Keyun. National Institutes of Health; Estados UnidosFil: Siess, Don. Oregon Health and Science University; Estados UnidosFil: Burke, David. Oregon Health and Science University; Estados UnidosFil: Park, Byung S.. Oregon Health and Science University; Estados UnidosFil: Axthelm, Michael K. Oregon Health and Science University; Estados UnidosFil: Lewis, Anne. Oregon Health and Science University; Estados UnidosFil: Hirsch, Vanessa M.. National Institutes of Health; Estados UnidosFil: Graham, Barney S.. National Institutes of Health; Estados UnidosFil: Mascola, John R.. National Institutes of Health; Estados UnidosFil: Sacha, Jonah B.. Oregon Health and Science University; Estados UnidosFil: Haigwood, Nancy L.. Oregon Health and Science University; Estados Unido
Efficacy and tolerability of the single-pill combination of aliskiren 300 mg/amlodipine 10 mg in hypertensive patients not controlled by olmesartan 40 mg/amlodipine 10 mg
No full textHuman memory CD8+ T-cells exhibit an intrinsic metabolic advantage as reflected by increased mitochondrial functionality and high glycolytic potential
No full textIntrinsic differences between na•ve and memory CD8+ T-cells affect both quality and quantity of cognate antigen response. Cellular immune function and metabolic pathways are closely linked. The metabolic repertoire of na•ve and memory T-cells remains largely unknown. Here we assessed key metabolic features of human na•ve and effector-memory CD8+ T-cells under basal, metabolic stress, and activating conditions. Basal mitochondrial respiration was similar in both subsets. Memory cells, however, possessed more complex, tubular mitochondria, and displayed greater respiratory capacity and enhanced fatty acid oxidation. Basal glycolysis was also comparable in both subsets. Memory cells, however, showed an exclusive capacity to rapidly upregulate glycolysis after mitochondrial respiration blockage. In line with this finding, effector memory CD8+ T-cells expressed more cytoplasmic GAPDH levels with enhanced activity compared to na•ve CD8+ T-cells.
Protective immunologic memory depends on antigen-experienced T-cells that are able to: (a) rapidly acquire effector function and (b) expand as secondary effector cells (Masopust and Picker, 2012). The clonal re-expansion of memory cells requires aerobic glycolysis (Warburg effect) in order to meet added biosynthetic and energetic demands (Vander Heiden et al., 2009). The metabolic requirements of rapidly responding effector memory CD8+ T-cells are unknown. Here we show that human effector memory CD8+ T-cells possess the intrinsic ability to upregulate aerobic glycolysis with unexpected rapid dynamics. In contrast to prototypical aerobic switch in activated T-cells, this early phase is insensitive to blockage of mTORC1, a known regulator of glucose metabolism in proliferating T-cells (Finlay et al., 2012; Fox et al., 2005). CD28 signaling via mTORC2 and AKT is required to sustain this early increased glycolyis. Importantly, preventing this early glycolytic phase by either blocking AKT activity or glucose deprivation, led to an impairment of IFN-gamma secretion.
Therefore, increased metabolic capacities in effector memory CD8+ T-cells promote a primed state to immediately support high glycolytic activity upon activation. This early glycolytic phase is prerequisite for immediate effector function and therefore linking metabolic features with CD8+ T-cells recall functionality.
Our findings established differential metabolic repertoires between na•ve and effector-memory CD8+ T-cells, with implications for strategies aiming to therapeutically manipulate CD8+ T-cell memory
Full genome sequence analysis of a novel adenovirus of rhesus macaque origin indicates a new simian adenovirus type and species
No full textAbstractMultiple novel simian adenoviruses have been isolated over the past years and their potential to cross the species barrier and infect the human population is an ever present threat. Here we describe the isolation and full genome sequencing of a novel simian adenovirus (SAdV) isolated from the urine of two independent, never co-housed, late stage simian immunodeficiency virus (SIV)-infected rhesus macaques. The viral genome sequences revealed a novel type with a unique genome length, GC content, E3 region and DNA polymerase amino acid sequence that is sufficiently distinct from all currently known human- or simian adenovirus species to warrant classifying these isolates as a novel species of simian adenovirus. This new species, termed Simian mastadenovirus D (SAdV-D), displays the standard genome organization for the genus Mastadenovirus containing only one copy of the fiber gene which sets it apart from the old world monkey adenovirus species HAdV-G, SAdV-B and SAdV-C
The ingenol-based protein kinase C agonist GSK445A is a potent inducer of HIV and SIV RNA transcription
No full textAuthor summaryAntiretroviral therapy (ART) is not a definitive cure HIV infection, in part, because the virus is able to integrate its genetic material in the host cell and remain in a dormant but fully replication-competent form during ART. These latently-infected cells can persist for long periods of time and remain hidden from the host's immune system. If ART is stopped, the virus can reactivate from this pool of infected cells and resume HIV replication and disease progression. As such, finding and eliminating cells with latent HIV infection is priority for HIV cure research. One approach is to use compounds referred to as latency-reversing agents, that can induce HIV reactivation during ART. The goal of this approach is to facilitate elimination of infected cells by the virus itself once it reactivates or by the host's immune system, once virus induction renders the cells detectable by the immune system, while also preventing the virus from infecting new cells due to the continued presence of ART. In this study we report on the activity of a novel latency-reversing agent called GSK445A, a potent activator of the enzyme protein kinase C (PKC). We show that GSK445A can induce HIV and simian immunodeficiency virus (SIV) latency reversal in vitro and has a tolerable saftey profile in nonhuman primates that should permit further testing of this PKC-agonist in strategies to cure HIV.
Activation of the NF-kappa B signaling pathway by Protein Kinase C (PKC) agonists is a potent mechanism for human immunodeficiency virus (HIV) latency disruption in vitro. However, significant toxicity risks and the lack of evidence supporting their activity in vivo have limited further evaluation of PKC agonists as HIV latency-reversing agents (LRA) in cure strategies. Here we evaluated whether GSK445A, a stabilized ingenol-B derivative, can induce HIV/simian immunodeficiency virus (SIV) transcription and virus production in vitro and demonstrate pharmacological activity in nonhuman primates (NHP). CD4(+) T cells from people living with HIV and from SIV+ rhesus macaques (RM) on antiretroviral therapy (ART) exposed in vitro to 25 nM of GSK445A produced cell-associated viral transcripts as well as viral particles at levels similar to those induced by PMA/Ionomycin, indicating that GSK445A can potently reverse HIV/SIV latency. Importantly, these concentrations of GSK445A did not impair the proliferation or survival of HIV-specific CD8(+) T cells, but instead, increased their numbers and enhanced IFN-gamma production in response to HIV peptides. In vivo, GSK445A tolerability was established in SIV-naive RM at 15 mu g/kg although tolerability was reduced in SIV-infected RM on ART. Increases in plasma viremia following GSK445A administration were suggestive of increased SIV transcription in vivo. Collectively, these results indicate that GSK445A is a potent HIV/SIV LRA in vitro and has a tolerable safety profile amenable for further evaluation in vivo in NHP models of HIV cure/remission
Risk Profiles and Treatment Patterns in Atrial Fibrillation Patients with Chronic Kidney Disease Receiving or not Receiving Anticoagulation Therapy
No full textCARDIAC MAGNETIC RESONANCE IMAGING AND PROGNOSIS IN ST-ELEVATION MYOCARDIAL INFARCTION: DATA FROM 1217 PATIENTS DERIVED FROM MULTICENTER STUDIES
No full textARCH+ : Zeitschrift für Architekten, Stadtplaner, Sozialarbeiter und kommunalpolitische Gruppen
No full textARCH+ : ZEITSCHRIFT FÜR ARCHITEKTEN, STADTPLANER, SOZIALARBEITER UND KOMMUNALPOLITISCHE GRUPPEN
ARCH+: Zeitschrift für Architektur und Urbanismus (-)
ARCH+ : Zeitschrift für Architekten, Stadtplaner, Sozialarbeiter und kommunalpolitische Gruppen (1981, Jg. 13, H. 55-57/58, [59], 60) (-)
Heft 55: Kampf um Selbsthilfe (-)
Contents ([1])
Architekturkritik (2)
Städtebau und Herrschaft. Zu den Ausstellungen in Venedig, Florenz und Vicenza (2)
Bedrohte Zeugen der Industriegeschichte (8)
Aquarellierte Architektur (9)
Stobbes Berliner Traum - Ein Bildkommentar (11)
Politische Auseinandersetzung um Selbsthilfe (12)
Anstelle eines Editorials: Zwei Stellungnahmen. Nachdruck aus dem Kölner Volksblatt vom 12.12.1980 (12)
Ausweg Selbsthilfe? (14)
Instandsetzungsforderung und Hausbesetzung (19)
10 Jahre Instandbesetzungsforderung (20)
Zur Instandbesetzerbewegung in Berlin. Stellungnahmen aus dem Institut für Stadt- und Regionalplanung (ISR) der TU Berlin (25)
Selbsthilfe: hat ihre Geschichte eine Zukunft (25)
Selbsthilfe als Reformbewegung. Der Kampf der Wiener Siedler nach dem 1. Weltkrieg (25)
Selbsthilfeprojekte: alltägliche Kämpfe und Konflikte (41)
Hast Du keins - leih Dir eins. Erfahrungen aus den Häuserkämpfen in Hannover und anderswo (41)
Genossenschaftsprojekt: "Alternative eG" Muskauer Straße 20 (44)
Von der geförderten zur gefärdeten Selbsthilfe. Vier Beispiele "autonomer" Selbsthilfe aus Berlin-Kreuzberg (47)
Sozialer Wohnungsbau und Selbstbau? (52)
Selbstbau während des Studiums. Zusammenarbeit von Studenten und Bauherr als Modell? (53)
Serie: Planerroman (55)
Distanz. Stationen eines Planerlebens (2. Teil) (55)
Berichte, Rezensionen, Leserbriefe (60)
Alternativen in der Kommunalpolitik? (60)
Heft 56: Die 50er Jahre - oder warum es keine deutsche Architektur gibt (-)
Inhaltsverzeichnis ([1])
Architektur aktuell (2)
Karl Friedrich Schinkel made in GDR (2)
Denkmalpflege: Schützen und Gebrauchen - ein Widerspruch? Briefwechsel zwischen Julius Posener und Dieter Hoffmann-Axthelm über dessen "Plädoyer für die Abschaffung der Denkmalpflege" in ARCH+ 54 (7)
... I want it to help, not to hinder me ... Neue Erfahrungen im Umgang mit Raum. Die "Women's School of Planning and Architecture", USA (10)
Die 50er Jahre - oder warum es keine deutsche Architektur gibt (13)
Deutschland 1945-80 - Der Architektur ohne Architektur (13)
Nierentischberg auf Rastergrund - ein Bildkommentar (14)
Die fünfziger Jahre. Persönliche Erinnerungen an die Zeit des Wiederaufbaus (22)
Das nationale Aufbauprogramm der DDR (28)
[Eingeheftete Beilage:] ARCH+ Jahrgangsverzeichnis 1980 (-)
Zwischen Heimatschutzstil und dynamischem Modernismus (32)
Aufgelockert und gegliedert. Wohnungsbau der 50er Jahre (36)
Die Zukunft der "Neuen Vahr". "Denkmalschutz" oder Vitalisierung? (39)
Gewalt in der Stadt (41)
Stadt als Ort struktureller Gewalt - Jugendkrawall als Gegenwehr (41)
"Gewalt in der Stadt" Bericht über die Tagung der Evangelischen Akademie Berlin im Februar 1981 (47)
Zur Diskussion: Alternativen im Wohnungsbau (48)
Sozialer Wohnungsbau: Vorschläge zur Humanisierung (48)
Serie: Planerroman (52)
Distanz. Stationen eines Planerlebens (3.Teil) (52)
Rezensionen, Filmberichte, kurz notiert (55)
Heft 57/58: Ein neuer Realismus in der Architektur? ([1])
Inhalt (2)
Inhaltsverzeichnis (2)
Editorial: Ein neuer Realismus in der Architektur? (3)
Architektur aktuell (4)
Der Mythos. Westberlin zu Füßen Schinkels (4)
Zwei Seiten einer Medaille, die aus dem Hut erst noch gezaubert werden muß (6)
Vorbilder - Lebensbilder - Wirkungen (1) (8)
Das mißglückte Interview - Ludwig Leo (8)
Lore Ditzen im Gespräch mit Oswald M. Ungers (12)
Lore Ditzen im Gespräch mit Hardt Waltherr Hämer (17)
Sozialräumliche Nutzungsanalysen (18)
Werkberichte (21)
Gerhard Auer. Quartier für tausend Studenten: Karlshof Darmstadt (21)
Andreas Brand. Festhalle Unna (24)
Günther Fischer. Standortbestimmung. Nettelbeckplatz Wedding, Berlin (26)
Ganz + Rolfes. Spielhaus Spandau, drei Wohnhäuser, Kreuzberg (28)
Goldapp + Klumpp. Komturstraße, Bremen, Tiergarten-Rauchstraße, Berlin, und andere gemeinsame Projekte (32)
Jacoby / Martin / Pächter. Das Brot des Bäckers und die Bauten der Architekten. Altenclub Rixdorf, Kindergartenstätte Britz (36)
Ernst Kasper. Sanierung Schnellengasse Eschweiler (40)
Wolfgang Pohl. Architektur in Deutschland - "Vater und Söhne". Bürgerhaus Hochdahl und andere Projekte (42)
Hartmut + Ingeborg Rüdiger. Wettbewerb Ackerhof Braunschweig (46)
[Eingeheftete Beilage:] ARCH+ Sonderdruck: "Steine aus Saarbrücken". Saarbrücker Erklärung für eine neue Wohnungspolitik, diskutiert auf der Jahrestagung des Deutschen Werkbundes vom 10. bis 14.06.1981 (-)
Arbeitsgemeinschaft Hans-Dieter Schaal u.a. Anregungen für eine neue Landschaftsgestaltung Bundesgartenschau Berlin 1985 (48)
Christoph Schulten. Architekt sein bedeutet für mich beides: Planen und selber Bauen. 3x Selbstbau (50)
Michael Wilkens mit der Arbeitsgruppe Stadt/Bau. Gebrauchswertorientierte Wohnbauplanung (52)
Vorbilder - Lebensbilder - Wirkungen (2) (55)
Lore Ditzen im Gespräch mit Giancarlo de Carlo (54)
Lore Ditzen im Gespräch mit Ralph Erskine (59)
z.B. München .. auch deutsche Architektur oder die späte Rache der Welfen ([62])
Wohnungspolitik (64)
Grundzüge der Wohnungspolitik in der BRD seit 1949 (64)
Subventionen für das Bauherrenmodell. Wohnungsbauförderung oder Geldverschwendung? (69)
Richtig oder falsch? (70)
Geschichte des sozialen Wohnungsbaus. Das Beispiel Bremen 1945-1980 (72)
Architekturkritik (78)
Schwierigkeiten mit der Moderne (78)
Berlin. Öffentliches Laster und private Tugend (Vices publics et vertus privèes) (84)
Serie: Planerroman (86)
Distanz. Stationen eines Planerlebens (4. Teil) (86)
Rezension (88)
Kurz notiert (89)
Heft 60: Kein Ort, nirgends – Auf der Suche nach Frauenräumen ([1])
Inhalt ([2])
Inhaltsverzeichnis ([2])
(Kein) Editorial (4)
Architektinnen im Beruf: kein Spielraum (5)
Aus meinem Leben. "... angesichts der Umstände eine erträgliche Lösung." (5)
Architektinnen und Planerinnen untersuchen ihre Arbeitsbedingungen (8)
Frauenbaustelle "Alibi-Klo" (10)
Ein Vorstellungsgespräch (11)
Arbeitsalltag: Traum und Wirklichkeit (12)
Frauenprojekte: neue Wege für Architektinnen (13)
Zwischenräume (13)
Frauen-Stadtteilzentrum in der Naunynstr. 72, Berlin (14)
Women's Development Corporation. "Wir wollen guten Wohnungsbau machen und Frauenarbeitsplätze schaffen ..." (15)
"Wir arbeiten fest an unseren Träumen". Café Hydra: Frauen-Selbsthilfeprojekt Potsdamer Str. 139, Berlin (18)
Wo Außenseiterinnen wohnen. 1. Frauen-Sommer-Museum 1981. Ausstellung der Gruppe "freuen formen ihre stadt" (20)
Öffentlichkeit und Häuslichkeit: Ortssuche zwischen drinnen und draußen (21)
Frauen und Öffentlichkeit (21)
Frauen in der Stadt - Frauen in Dortmund. Frauenseminar an der Uni Dortmund (Beitrag zur Ausstellung "Wo Außenseiterinnen Wohnen") (31)
Frauen in der Stadt: Orte der Gewalt (36)
HEIM-lichkeiten. Gewalt gegen Frauen in der Stadt (35)
Tatorte. Orte der Gewalt im öffentlichen Raum (39)
Frauenalltag und Raumkonzepte: neue Orte schaffen (42)
Was ist feministische Architektur? (42)
Wie könnte eine nicht-sexistische Stadt aussehen? (47)
Einküchenhäuser. Ein Weg zu neuen Wohnmodellen? (52)
Der ganz normale Alltag der Elly M. (54)
Modernisierung kostet mehr als Geld (56)
Raumerfahrung und Raumwahrnehmung: Spurensuche (60)
Frauen - Räume - Raumerfahrung. Workshop (60)
Wohnbiographie (62)
Gescheiterte Translokationen (64
Impact of CMR parameters on clinical outcome after STEMI: data from a large multi-center study
No full textIntracoronary Compared With Intravenous Bolus Abciximab Application During Primary Percutaneous Coronary Intervention in ST-Segment Elevation Myocardial Infarction Cardiac Magnetic Resonance Substudy of the AIDA STEMI Trial
No full textObjectivesThe aim of the AIDA STEMI (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction) cardiac magnetic resonance (CMR) substudy was to investigate potential benefits of intracoronary versus intravenous abciximab bolus administration on infarct size and reperfusion injury in ST-segment elevation myocardial infarction.BackgroundThe AIDA STEMI trial randomized 2,065 patients to intracoronary or intravenous abciximab and found similar rates of major adverse cardiac events at 90 days with significantly less congestive heart failure in the intracoronary abciximab group. CMR can directly visualize myocardial damage and reperfusion injury, thereby providing mechanistic and pathophysiological insights.MethodsWe enrolled 795 patients in the AIDA STEMI CMR substudy. CMR was completed within 1 week after ST-segment elevation myocardial infarction. Central core laboratory–masked analyses for quantified ventricular function, volumes, infarct size, microvascular obstruction, hemorrhage, and myocardial salvage were performed.ResultsThe area at risk (p = 0.97) and final infarct size (16% [interquartile range: 9% to 25%] versus 17% [interquartile range: 8% to 25%], p = 0.52) did not differ significantly between the intracoronary and the intravenous abciximab groups. Consequently, the myocardial salvage index was similar (52 [interquartile range: 35 to 69] versus 50 [interquartile range: 29 to 69], p = 0.25). There were also no differences in microvascular obstruction (p = 0.19), intramyocardial hemorrhage (p = 0.19), or ejection fraction (p = 0.95) between both treatment groups. Patients in whom major adverse cardiac events occurred had significantly larger infarcts, less myocardial salvage, and more pronounced ventricular dysfunction.ConclusionsThis largest multicenter CMR study in ST-segment elevation myocardial infarction patients to date demonstrates no benefit of intracoronary versus intravenous abciximab administration on myocardial damage and/or reperfusion injury. Infarct size determined by CMR was significantly associated with major adverse cardiac events. (Abciximab i.v. Versus i.c. in ST-elevation Myocardial Infarction [AIDA STEMI]; NCT00712101
