Targeted disruption of mouse long-chain acyl-CoA dehydrogenase gene reveals crucial roles for fatty acid oxidation

Abnormalities of fatty acid metabolism are recognized to play a significant role in human disease, but the mechanisms remain poorly understood. Long-chain acyl-CoA dehydrogenase (LCAD) catalyzes the initial step in mitochondrial fatty acid oxidation (FAO). We produced a mouse model of LCAD deficiency with severely impaired FAO. Matings between LCAD +/− mice yielded an abnormally low number of LCAD +/− and −/− offspring, indicating frequent gestational loss. LCAD −/− mice that reached birth appeared normal, but had severely reduced fasting tolerance with hepatic and cardiac lipidosis, hypoglycemia, elevated serum free fatty acids, and nonketotic dicarboxylic aciduria. Approximately 10% of adult LCAD −/− males developed cardiomyopathy, and sudden death was observed in 4 of 75 LCAD −/− mice. These results demonstrate the crucial roles of mitochondrial FAO and LCAD in vivo.     

Nicht-invasive Beatmung

Zum Thema Die nicht-invasive Beatmung (NIV) über eine Maske erm?glicht bei vielen Patienten eine effiziente Beatmung unter Vermeidung der Risiken und Nebenwirkungen der endotrachealen Intubation. Für die chronisch-obstruktive Lungenerkrankung (COPD) sind die Vorteile der Maskenbeatmung im Hinblick auf Beatmungsdauer, Dauer der Intensivbehandlung, Prognose und Behandlungskosten inzwischen relativ gut durch Studien belegt. Bei anderen Indikationen –“Nicht-COPD-Patienten”– erlauben die verfügbaren Daten noch kein gesichertes Urteil, rechtfertigen aber einen Behandlungsversuch auch au?erhalb von Studien in klinischer Routine. Nachteilig sind der initial h?here personelle Betreuungsaufwand bei NIV sowie die stark von der Erfahrung abh?ngige Erfolgsrate. Die wichtigste Voraussetzung für eine erfolgreiche nicht-invasive Beatmung in der Intensivmedizin ist die Bereitschaft von ?rzten und Pflegepersonal, eine ungewohnte Beatmungsphilosophie zu akzeptieren und die relativ einfache Technik der Maskenbeatmung zu erlernen. Bei Beherrschung der Technik kann die NIV aber eine wertvolle Hilfe vom Notarztwagen bis zur Intensivstation sein.     

Localisation of neuroendocrine tumours of the upper gastrointestinal tract.

In order to localise neuroendocrine tumours of the foregut type (that is, of the stomach, duodenum, and pancreas), 18 patients were studied prospectively by endoscopic ultrasonography, computed tomography, transabdominal ultrasonography, magnetic resonance imaging, and somatostatin receptor scintigraphy. These 18 patients had a total of 25 primary tumour lesions which were verified histologically in tissue obtained by surgery or by ultrasound or endoscopy guided biopsy. Tumours were found in the stomach (n = 1), duodenum (n = 6), pancreas (n = 17), and liver (n = 1). Endoscopic ultrasonography had the highest sensitivity for tumour detection, followed by somatostatin receptor scintigraphy, computed tomography, transabdominal ultrasonography, and magnetic resonance imaging (88%, 52%, 36%, 32%, and 24% respectively). Endoscopic ultrasonography was especially sensitive in tumours smaller than 2 cm in diameter (88% v somatostatin receptor scintigraphy 35%; computed tomography 12%; transabdominal ultrasonography 6%; and magnetic resonance imaging 0%). Of 17 tumours located in the pancreas, endoscopic ultrasonography showed a sensitivity of 94% (somatostatin receptor scintigraphy 47%; computed tomography 47%; transabdominal ultrasonography 41%; and magnetic resonance imaging 29%). Of eight extrapancreatic tumours, six were identified by endoscopic ultrasonography, five by somatostatin receptor scintigraphy, and only one by computed tomography, transabdominal ultrasonography, and magnetic resonance imaging. One neuroendocrine tumour that was not detected by endoscopic ultrasonography was correctly identified by somatostatin receptor scintigraphy. Endoscopic ultrasound allowed correct determination of the tumour size and tumour spread into parapancreatic structures, especially the large vessels (T stage), in all 14 patients operated upon. The lymph node stage (N stage) was correctly determined in 10 of these 14 patients. In summary, endoscopic ultrasonography and somatostatin receptor scintigraphy were the most sensitive imaging methods for the localisation of these tumours and should be used as early diagnostic procedures to accurately stage neuroendocrine tumours of the foregut type.     

Resistance to RevM10 inhibition reflects a conformational switch in the HIV-1 Rev response element

Nuclear export of certain HIV-1 mRNAs requires an interaction between the viral Rev protein and the Rev response element (RRE), a structured element located in the Env region of its RNA genome. This interaction is an attractive target for both drug design and gene therapy, exemplified by RevM10, a transdominant negative protein that, when introduced into host cells, disrupts viral mRNA export. However, two silent G->A mutations in the RRE (RRE61) confer RevM10 resistance, which prompted us to examine RRE structure using a novel chemical probing strategy. Variations in region III/IV/V of mutant RNAs suggest a stepwise rearrangement to RevM10 resistance. Mass spectrometry was used to directly assess Rev “loading” onto RRE and its variants, indicating that this is unaffected by RNA structural changes. Similarity in chemical footprints with mutant protein implicates additional host factors in RevM10 resistance.     

The house sparrow (Passer domesticus) as a sentinel for St. Louis encephalitis virus

Birds are the primary hosts for St. Louis encephalitis (SLE) virus in most of North America. Because the increased prevalence of antibody in House Sparrows (Passer domesticus) has been related to human cases, this species has been frequently used as a sentinel of SLE virus activity in urban areas. This study investigated the susceptibility of House Sparrows to two strains of SLE virus, measured antibody profiles, and evaluated the use of House Sparrows in an urban surveillance system. House Sparrows were susceptible to both strains of SLE virus inoculated, although not equally, and produced viremias sufficient to infect vector mosquitoes. Both hemagglutination-inhibiting (HI) and neutralizing (N) antibody developed rapidly and to high titers within 2 weeks after inoculation. Detectable humoral antibody began to disappear by 3 months, but persisted for 2 years in 27% for HI and 36% for N antibody of the surviving birds. However, all of the surviving birds were resistant to reinfection with SLE virus at 2 years after inoculation. The titer of HI antibody appeared to be useful in determining recent exposure to SLE virus. The experimental data on HI antibody development and persistence was related to field serologic data from House Sparrows. The monthly prevalences of SLE antibody for independent samples of sera from House Sparrows collected in Memphis, Tennessee, in 1980 were similar. SLE amplification in the House Sparrow population was delayed until September. The Memphis arbovirus surveillance system detected the amplification quickly, and responded with increased adult mosquito control in the focal areas. Urban surveillance of SLE utilizing House Sparrows as sentinels is discussed.     

Distribution and prevalence of Mermet virus infections in the central United States

Tests were run on 3,198 bird sera for neutralizing antibody of Mermet virus. The birds were mostly House Sparrows (Passer domesticus) captured in the central U.S. Antibody was detected in birds from Texas, Mississippi, Tennessee, Ohio, Indiana, Illinois, and Wisconsin, but not Kentucky or Missouri. Antibody prevalence differed by location and between years in similar locations. These results confirmed the widespread activity of Mermet virus in the central U.S., suggested irregular activity of the virus, and provided the first evidence that Mermet virus activity occurs in Mississippi, Indiana, and Wisconsin. No antibody to Mermet virus was found in paired sera from 966 humans with suspected arboviral infection.     

Immune responses to major histocompatibility complex homozygous lymphoid cells in murine F1 hybrid recipients: implications for transfusion-associated graft-versus-host disease

Graft-versus-host disease (GVHD) is currently encountered after bone marrow transplantation and transfusion. GVHD associated with transfusion (TA-GVHD) in apparently immunocompetent recipients has been recently reported with increasing frequency. A consistent finding in many of these cases is that the recipient received blood from a donor homozygous for one of the recipient's HLA haplotypes. However, the observed frequency of TA-GVHD is much lower than the estimated probability of this donor/recipient combination. The potential role of recipient immune responses in controlling TA-GVHD was investigated using an analogous murine model in which GVHD is induced by the injection of parental lymphoid cells into unirradiated F1 hybrid recipients. The effect of various immune manipulations of the recipient of GVHD induction was assessed by determining the number of donor lymphoid cells required to induce GVHD responses. Whereas depletion of recipient CD4+ cells increased the number of donor cells needed to induce GVHD, depletion of recipient CD8+ and natural killer cells resulted in fewer donor cells being needed to induce a GVHD response. These studies suggest a central role for functioning recipient CD8 and natural killer cells in the down-regulation of TA-GVHD development in recipients.     

Publikationsleistungen der Universitätskliniken für Anästhesiologie

Aim

This study assessed the publication performance of university departments of anesthesiology in Austria, Germany and Switzerland. The number of publications, original articles, impact factors and citations were evaluated.

Material and methods

A search was performed in PubMed to identify publications related to anesthesiology from 2001 to 2010. All articles from anesthesiology journals listed in the fields of anesthesia/pain therapy, critical care and emergency medicine by the “journal citation report 2013” in Thomson Reuters ISI web of knowledge were included. Articles from non-anaesthesiology journals, where the stem of the word anesthesia (anes*, anaes*, anäst*, anast*) appears in the affiliation field of PubMed, were included as well. The time periods 2001–2005 and 2006–2010 were compared. Articles were allocated to university departments in Austria, Germany and Switzerland via the affiliation field.

Results

A total of 45 university departments in Austria, Germany and Switzerland and 125,979 publications from 2,863 journals (65 anesthesiology journals, 2,798 non-anesthesiology journals) were analyzed. Of the publications 23?% could not be allocated to a given university department of anesthesiology. In the observation period the university department of anesthesiology in Berlin achieved most publications (n?=?479) and impact points (1,384), whereas Vienna accumulated most original articles (n?=?156). Austria had the most publications per million inhabitants in 2006-2010 (n=50) followed by Switzerland (n=49) and Germany (n=35). The number of publications during the observation period decreased in Germany (0.5?%), Austria (7?%) and Switzerland (8?%). Tables 2 and 4–8 of this article are available at Springer Link under Supplemental.

Conclusions

The research performance varied among the university departments of anesthesiology in Germany, Austria and Switzerland whereby larger university departments, such as Berlin or Vienna published most. Publication output in Germany, Austria and Switzerland has decreased. Data processing in PubMed should be improved.     

Timing the fearful brain: unspecific hypervigilance and spatial attention in early visual perception

Numerous studies suggest that anxious individuals are more hypervigilant to threat in their environment than nonanxious individuals. In the present event-related potential (ERP) study, we sought to investigate the extent to which afferent cortical processes, as indexed by the earliest visual component C1, are biased in observers high in fear of specific objects. In a visual search paradigm, ERPs were measured while spider-fearful participants and controls searched for discrepant objects (e.g. spiders, butterflies, flowers) in visual arrays. Results showed enhanced C1 amplitudes in response to spatially directed target stimuli in spider-fearful participants only. Furthermore, enhanced C1 amplitudes were observed in response to all discrepant targets and distractors in spider-fearful compared with non-anxious participants, irrespective of fearful and non-fearful target contents. This pattern of results is in line with theoretical notions of heightened sensory sensitivity (hypervigilance) to external stimuli in high-fearful individuals. Specifically, the findings suggest that fear facilitates afferent cortical processing in the human visual cortex in a non-specific and temporally sustained fashion, when observers search for potential threat cues.