Human Immunodeficiency Virus type 1 Endocytic Trafficking Through Macrophage Bridging Conduits Facilitates Spread of Infection

Bridging conduits (BC) sustain communication and homeostasis between distant tethered cells. These are also exploited commonly for direct cell-to-cell transfer of microbial agents. Conduits efficiently spread infection, effectively, at speeds faster than fluid phase exchange while shielding the microbe against otherwise effective humoral immunity. Our laboratory has sought to uncover the mechanism(s) for these events for human immunodeficiency virus type one (HIV-1) infection. Indeed, in our prior works HIV-1 Env and Gag antigen and fluorescent virus tracking were shown sequestered into endoplasmic reticulum-Golgi organelles but the outcomes for spreading viral infection remained poorly defined. Herein, we show that HIV-1 specifically traffics through endocytic compartments contained within BC and directing such macrophage-to-macrophage viral transfers. Following clathrin-dependent viral entry, HIV-1 constituents bypass degradation by differential sorting from early to Rab11+ recycling endosomes and multivesicular bodies. Virus-containing endocytic viral cargoes propelled by myosin II through BC spread to neighboring uninfected cells. Disruption of endosomal motility with cytochalasin D, nocodasole and blebbistatin diminish intercellular viral spread. These data lead us to propose that HIV-1 hijacks macrophage endocytic and cytoskeletal machineries for high-speed cell-to-cell spread

Manifesto on small airway involvement and management in asthma and chronic obstructive pulmonary disease:an Interasma (Global Asthma Association - GAA) and World Allergy Organization (WAO) document endorsed by Allergic Rhinitis and its Impact on Asthma (ARIA) and Global Allergy and Asthma European Network (GA2LEN)

Evidence that enables us to identify, assess, and access the small airways in asthma and chronic obstructive pulmonary disease (COPD) has led INTERASMA (Global Asthma Association) and WAO to take a position on the role of the small airways in these diseases. Starting from an extensive literature review, both organizations developed, discussed, and approved the manifesto, which was subsequently approved and endorsed by the chairs of ARIA and GA2LEN. The manifesto describes the evidence gathered to date and defines and proposes issues on small airway involvement and management in asthma and COPD with the aim of challenging assumptions, fostering commitment, and bringing about change. The small airways (defined as those with an internal diameter <2 mm) are involved in the pathogenesis of asthma and COPD and are the major determinant of airflow obstruction in these diseases. Various tests are available for the assessment of the small airways, and their results must be integrated to confirm a diagnosis of small airway dysfunction. In asthma and COPD, the small airways play a key role in attempts to achieve disease control and better outcomes. Small-particle inhaled formulations (defined as those that, owing to their size [usually <2 μm], ensure more extensive deposition in the lung periphery than large molecules) have proved beneficial in patients with asthma and COPD, especially those in whom small airway involvement is predominant. Functional and biological tools capable of accurately assessing the lung periphery and more intensive use of currently available tools are necessary. In patients with suspected COPD or asthma, small airway involvement must be assessed using currently available tools. In patients with subotpimal disease control and/or functional or biological signs of disease activity, the role of small airway involvement should be assessed and treatment tailored. Therefore, the choice between large- and small-particle inhaled formulations must reflect the physician’s considerations of disease features, phenotype, and response to previous therapy. This article is being co-published in Asthma Research and Practice and the World Allergy Organization Journal

Labor- und Feldversuche zur mikrobiologischen Sanierung von altoelkontaminierten Raffineriestandorten Endbericht

To develop techniques for the microbial on-site (pile) and in-situ reclamation, laboratory and pilot-scale experiments were performed at a contaminated former waste oil refinery site. Concerning the pile experiments, volatile pollutants like chlorinated hydrocarbons and benzene derivatives (BTEX) were stripped almost completely during excavation and soil preparation. The concentrations of lower molecular mass polychlorinated hydrocarbons (PCB) were reduced by about 50% during a pile treatment of more than 1 year. The mineral oil hydrocarbons were reduced by about 70% independent from methods and starting concentrations. The remaining fraction was of high molecular mass, not leachable and not bioavailable. For the microbiological in-situ remediation of saturated aquifers, an optimal oxygen supply of microorganisms is of greatest importance. The electron acceptors tested were hydrogen peroxide (H_2O_2), technical grade oxygen (O_2), and nitrate. H_2O_2 was recommended: it provides the best O_2 supply and caused the highest microbial degradation activity. Nitrate can be applied additionally. Due to a lower mineralisation efficiency compared to H_2O_2, it results in a 'pre-remediation' of the anaerobic areas of the aquifer. Chlorinated hydrocarbons and BTEX were preferentially washed out hydraulically. The result of R and D project were directly transferred into execution plans for the microbial on-site and in-situ remediation at the site. Due to a high H_2O_2 decay and a resulting formation of O_2 bubbles in the aquifer, the technical reclamation will include a pulsed infiltration. A monitoring program was elaborated for the control and optimisation of the in-situ remediation. (orig.)Available from TIB Hannover: F95B2542+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany); Hessische Industriemuell GmbH, Wiesbaden (Germany). Bereich AltlastensanierungsgesellschaftDEGerman

Mikrobielle Sanierung von TNT-kontaminierten Boeden des Standortes Hessisch Lichtenau im Rahmen des Verbundforschungsprojektes Ruestungsaltlasten. Teilvorhaben 2 Endbericht

SIGLEAvailable from TIB Hannover: F96B98+a / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Variability of serial lipoprotein-associated phospholipase A2 measurements in post myocardial infarction patients: Results from the AIRGENE Study Center Augsburg.

Of the numerous emerging biomarkers for coronary heart disease (CHD), lipoprotein-associated phospholipase A(2) (Lp-PLA(2)), an enzyme involved in lipid metabolism and inflammatory pathways, seems to be a promising candidate. Implementation of Lp-PLA(2) measurement into clinical practice, however, requires data on the reliability of such measurements. METHODS: We measured Lp-PLA(2) concentrations by ELISA in blood samples drawn from 200 post-myocardial infarction patients (39-76 years) at 6 monthly intervals between May 2003 and February 2004, for a total of 1143 samples. We estimated analytical, within-individual, and between-individual variation, the critical difference, and the intraclass correlation coefficient of reliability (ICC) to assess the reliability of serial Lp-PLA(2) measurements. RESULTS: The mean (SD) plasma Lp-PLA(2) concentration for the study participants was 188.7 (41.8) microg/L, with no significant difference between men and women. The analytical CV for Lp-PLA(2) was 4.4%, the within-individual biological CV was 15%, and the between-individual CV was 22%. The ICC was 0.66. An important part of the total variation in plasma Lp-PLA(2) concentration was explained by the between-individual variation (as a percentage of the total variance, 66.1%), whereas the within-individual variance was 31.3%. The analytical variance was as low as 2.6%. CONCLUSIONS: Between-individual variation in Lp-PLA(2) concentration was substantially greater than within-individual variation. In general, our data demonstrate considerable stability and good reproducibility of serial Lp-PLA(2) measurements, results that compared favorably with those for the more commonly measured lipid markers

Erarbeitung von Programmen zur Ueberwachung von altlastverdaechtigen Flaechen und Altlasten. Bd. 1 und 2

At present, the monitoring of contaminated sites in the Federal States of Germany is managed in different ways: The aim of the research project was to formulate minimum demands for monitoring programmes on the basis of the German Federal Soil Protection Act (Bundes-Bodenschutzgesetz). The technological basis was developed and discussed in detail and model monitoring programmes were derived for volatile halogenated hydrocarbons, mineral oil hydrocarbons, aromatic hydrocarbons, polycyclic aromatic hydrocarbons, heavy metals, contaminated sites with domestic waste and a complex site with different groups of contaminants. It is demonstrated in four case examples that these models can be used in practice. (orig.)Published in two volumesAvailable from TIB Hannover: RN 8422(1999,96,1): RN 8422(1999,96,2) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit, Bonn (Germany)DEGerman

Labor- und Felduntersuchungen zur mikrobiellen Sanierung von Altoel-kontaminierten Raffineriestandorten Abschlussbericht

Am Beispiel eines ehemaligen Altoelraffinerie-Standortes wurden mikrobielle on-site-(Mieten-) und in-situ-Sanierungstechniken im Labor- und Pilotmassstab untersucht. Beim Mietenverfahren wurden leichtfluechtige Schadstoffe waehrend des Bodenaushubs und der Bodenaufbereitung fast vollstaendig ausgetrippt. Die Konzentration niederchlorierter Polychlorierter Biphenyle (PCB) wird durch die Mietenbehandlung um bis zu 50% verringert. Mineraloele enthalten Kohlenwasserstoff-Fraktionen unterschiedlicher mikrobieller Abbaubarkeit, abhaengig von Molekuelgroesse und -struktur. Die untersuchten Altoel-kontaminierten Boeden zeigten nach einer Mietenbehandlung einen biologisch schwer abbaubaren Restgehalt von ca. 25% der Ausgangsbelastung, unabhaengig vom Verfahren und von der Ausgangskonzentration. Ursache ist eine mangelnde Bioverfuegbarkeit, nicht jedoch das biologische Abbaupotential. Der Erfolg einer in-situ-Sanierung der gesaettigten Zone wird entscheidend durch die Verfahrenstechnik fuer eine optimale dreidimensionale Versorgung des Untergrundes mit Naehrstoffen und Elektroakzeptoren bestimmt. Nitrat fuehrt im Vergleich zu Sauerstoff oder H_2O_2 zu einer geringeren Endmineralisierung. (orig.)Taking a former waste oil refinery site as an example, microbial on-site-clamp and in-situ reclamation techniques were tested in laboratory and pilot scale. Volatile pollutants are stripped almost completely during soil excavation and preparation. The concentration of polychlorinated biphenyls (PCB) with 6 or less chlorine atoms was reduced by clamp processing significantly (up to 50%). Mineral oils contain hydrocarbon fractions of different microbial degradability depending on molecular size and structure. After clamp processing, waste oil contaminted soils showed a non-degradable residue of about 25% of the initial contamination, regardless of technique or initial concentration, due to the lack of bioavailability, but not to the biological degradation potential. The success of an in-situ reclamation is determined by the process technique in order to provide the aquifer with an optimum of nutrients and electron acceptors. Nitrate gave less mineralization than oxygen or hydrogen peroxide. (orig.)Available from TIB Hannover: F93B168 / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekSIGLEBundesministerium fuer Forschung und Technologie (BMFT), Bonn (Germany)DEGerman

Ermittlung von Altoelverrmeidungspotentialen

One of the most important aims of the future cycle economy is the preservation of natural resources by avoidance of wastes. In the present research project, potentials for the avoidance of used oil were investigated. For the years 1992 and 1993, detailed mass balances for most lubricants were worked out. Lubricant losses into the environment were quantified according to their different entry pathways and the harmfulness for the environment was assessed. Forecasts for future lubricants demand and used oil quantities are given and proposals for the reduction of lubricants input into the environment are formulated. Potential reduction of used oil quantities in the next years is estimated at 29%. (orig.)Wesentliches Ziel der zukuenftigen Kreislaufwirtschaft ist es, Ressourcenschonung mit hoechster Prioritaet durch Vermeidung von Abfaellen zu erreichen. Im Hinblick auf die neue Altoelverordnung wurden im vorliegenden Forschungsvorhaben moegliche Vermeidungspotentiale fuer Altoele untersucht. Fuer alle mengenmaessig bedeutenden Schmierstoffsorten wurden fuer die Jahre 1992 und 1993 detaillierte Stoffbilanzen erstellt. Dabei wurden die aus Frischoelabsatz und Altoelsammelmenge resultierenden Verlustmengen hinsichtlich ihrer Eintragspfade in die Umwelt quantifiziert und die Schaedlichkeit des Umwelteintrags bewertet. Unter Beruecksichtigung neuester Technologien bei Kfz-Motoren, Maschinen und Aggregaten sowie verbesserter Schmierstoffprodukte werden Prognosen zum kuenftigen Frischoelbedarf und Altoelaufkommen angestellt. Es werden Vorschlaege zu Massnahmen und Regelungen formuliert, die zu einer Verminderung des Schmierstoffeintrags in die Umwelt und einer verbesserten Altoellogistik beitragen koennen. Die in den naechsten Jahren moegliche Verringerung des Altoelaufkommens wird auf 29% geschaetzt. (orig.)SIGLEAvailable from TIB Hannover: RN 8422(1997,16) / FIZ - Fachinformationszzentrum Karlsruhe / TIB - Technische InformationsbibliothekBundesministerium fuer Umwelt, Naturschutz und Reaktorsicherheit, Bonn (Germany)DEGerman