Insulin-like growth factor-binding protein-1 (IGFBP-1) regulates human schwannoma proliferation, adhesion and survival.

Merlin is a tumour suppressor involved in the development of a variety of tumours including mesotheliomas. Neurofibromatosis type 2 (NF2), a dominantly inherited tumour disease, is also caused by loss of merlin. NF2 patients suffer from multiple genetically well-defined tumours, schwannomas are most frequent among those. Using our in vitro model for human schwannoma, we found that schwannoma cells display enhanced proliferation because of the overexpression/activation of platelet-derived growth factor receptor and ErbB2/3, increased cell-matrix adhesion because of the overexpression of integrins, and decreased apoptosis. Mechanisms underlying schwannomas basal proliferation and cell-matrix adhesion are not understood. Here, we investigated insulin-like growth factor-binding protein-1 (IGFBP-1), which is expressed and released from central nervous system tumours and strongly overexpressed in schwannoma at the mRNA level. IGFBP-1 acts via ß1-integrin and focal-adhesion-kinase (FAK), which are strongly overexpressed and basally activated in schwannoma. Using short hairpin RNA knockdown, small inhibitors and recombinant IGFBP-1, we demonstrate that schwannoma cells, in contrast to Schwann cells, release IGFBP-1 that activates the Src/FAK pathway, via integrin ß1, potentiating schwannoma's proliferation and cell-matrix adhesion. We show that FAK localizes to the nucleus and Src triggers IGFBP-1 production. Further, we observed downregulation of the tumour-suppressor phosphatase and tensin homolog in schwannoma cells leading to increased activity of anti-apoptotic AKT. Thus, IGFBP-1/integrin ß1/Src/FAK pathway has a crucial role in merlin-related tumourigenesis and therefore represents an important therapeutic target in the treatment of merlin-deficient tumours.

[Airway management in the German air rescue service]. / Atemwegsmanagement im deutschen Luftrettungsdienst.

BACKGROUND: The equipment carried in rescue helicopters concerning airway management is not standardized in Germany. The current DIN/EN equipment regulations are not detailed for every single item resulting in differences between the various rescue bases. The aim of this survey was to show existing differences in airway management equipment. METHODS: All 72 German air rescue helicopters listed in the ADAC air rescue stations atlas 2006/2007 received a questionnaire. RESULTS: A total of 64 bases returned the questionnaire (88.9%). The most frequent types of supraglottic airway equipment were laryngeal masks (67.2%), Combitubes (32.8%) and laryngeal tubes (29.7%). Cricothyrotomy sets were more frequent (68.8%) than tracheostomy sets (35.9%). Of the bases 18.8% had masks suitable for non-invasive ventilation (NIV). All helicopters were equipped to carry out capnometry. CONCLUSIONS: The rescue helicopters were found to have differences with respect to the equipment carried for airway management. Medical treatment according to current guidelines is possible on almost all bases.

[Equipment of a land-based emergency medical service in Bavaria: a questionnaire]. / Ausstattung bodengebundener Notarztrettungsmittel in Bayern: Eine Umfrage.

BACKGROUND: Currently valid DIN regulations concerning the emergency equipment in physician-staffed rescue vehicles are not well defined for every single item. This leads to variations in the equipment in different ambulances. The aim of this study was to demonstrate the differences with some exemplary equipment purchases. METHODS: All 218 physician-staffed rescue vehicles in Bavaria received a questionnaire asking for current emergency medical equipment and planned items. RESULTS: A reply was received from 177 of the 218 bases (81%). The main results were that 88% of all bases had a 12-lead ECG, a portable emergency ventilator was available at 93% of all bases, 77% had alternative airway management devices (set for emergency coniotomy 71%, laryngeal mask 26%), expiratory CO(2 )measuring was available at 32% and 31 bases (18%) had fibrinolytic drugs in the emergency vehicles. CONCLUSIONS: There are vast differences among the emergency physician-staffed ambulances concerning the equipment which means that medical treatment according to current recommendations is not always possible at all bases.

Global impact and application of the anaerobic ammonium-oxidizing (anammox) bacteria.

In the anaerobic ammonium oxidation (anammox) process, ammonia is oxidized with nitrite as primary electron acceptor under strictly anoxic conditions. The reaction is catalysed by a specialized group of planctomycete-like bacteria. These anammox bacteria use a complex reaction mechanism involving hydrazine as an intermediate. The reactions are assumed to be carried out in a unique prokaryotic organelle, the anammoxosome. This organelle is surrounded by ladderane lipids, which make the organelle nearly impermeable to hydrazine and protons. The localization of the major anammox protein, hydrazine oxidoreductase, was determined via immunogold labelling to be inside the anammoxosome. The anammox bacteria have been detected in many marine and freshwater ecosystems and were estimated to contribute up to 50% of oceanic nitrogen loss. Furthermore, the anammox process is currently implemented in water treatment for the low-cost removal of ammonia from high-strength waste streams. Recent findings suggested that the anammox bacteria may also use organic acids to convert nitrate and nitrite into dinitrogen gas when ammonia is in short supply.

Isolation and properties of obligately chemolithoautotrophic and extremely alkali-tolerant ammonia-oxidizing bacteria from Mongolian soda lakes.

Five mixed samples prepared from the surface sediments of 20 north-east Mongolian soda lakes with total salt contents from 5 to 360 g/l and pH values from 9.7 to 10.5 were used to enrich for alkaliphilic ammonia-oxidizing bacteria. Successful enrichments at pH 10 were achieved on carbonate mineral medium containing 0.6 M total Na(+) and < or =4 mM NH(4)Cl. Five isolates (ANs1-ANs5) of ammonia-oxidizing bacteria capable of growth at pH 10 were obtained from the colonies developed on bilayered gradient plates. The cells were motile and coccoid, with well-developed intracytoplasmic membranes (ICPM) and carboxysomes. At pH 10.0, ammonia was toxic for growth at concentrations higher than 5 mM NH(4)Cl. The bacteria were able to grow within the salinity range of 0.1-1.0 M of total Na+ (optimum 0.3 M). In media containing 0.3-0.6 M total Na(+), optimal growth in batch cultures occurred in the presence of a bicarbonate/carbonate buffer system within the pH range 8.5-9.5, with the highest pH limit at pH 10.5. At pH lower than 8.0, growth was slower, most probably due to decreasing free ammonia. The pH profile of the respiratory activity was broader, with limits at 6.5-7.0 and 11.0 and an optimum at 9.5-10.0. In pH-controlled, NH(3)-limited continuous culture, isolate ANs5 grew up to pH 11.3, which is the highest pH limit known for ammonia-oxidizing bacteria so far. This showed the existence of extremely alkali-tolerant ammonia-oxidizing bacteria in the soda lakes. Comparative 16S rDNA sequence analysis of the five isolates demonstrated that they possess identical 16S rDNA genes and that they are closely related to Nitrosomonas halophila (sequence similarity 99.3%), a member of the beta-subclass of the Proteobacteria. This affiliation was confirmed by comparative sequence analysis of the amoA gene, encoding the active-site subunit of the ammonia-monoxygenase, of one of the isolates. DNA-DNA hybridization data further supported that the soda lake isolates are very similar to each other and represent an alkali-tolerant subpopulation of N. halophila whose species description is herewith amended.

Comparison of a continuous glucose-insulin-potassium infusion versus intermittent bolus application of insulin on perioperative glucose control and hormone status in insulin-treated type 2 diabetics.

STUDY OBJECTIVE: To compare the effect of two different perioperative insulin management regimes on patients undergoing either major surgery (vascular surgery) or minor surgery (vitrectomy). DESIGN: Prospective, double-blind randomized trial. PATIENTS: 48 insulin-treated type 2 diabetics aged 18 to 85 years were studied. SETTING: University medical center. INTERVENTIONS: Patients were divided into four groups of 12 patients each: Groups A and B (major surgery), Groups C and D (minor surgery). Group A and C patients were treated with a continuous modified glucose-insulin-potassium infusion according to blood glucose levels after intubation. Patients assigned to Groups B and D were treated with intermittent intravenous (IV) insulin injections when glucose levels exceeded 12 mmol L(-1). MEASUREMENTS: Glucose and potassium levels were measured every 15 minutes and 30 minutes during surgery and up to 4 hours post-surgery. Plasma levels of lactate, cortisol, glycerol, and free fatty acids were measured in arterial samples after intubation (S1), after extubation (S2), and 4 hours after surgery (S3). MAIN RESULTS: There were no significant differences of the patient characteristics among the four groups. There was no significant difference in the time course of plasma glucose levels and hormone variables measured among the four groups. One episode of hyperglycemia in Group D during the postoperative period was treated with 12 IV units of insulin. One patient in Group A and one in Group B received potassium intraoperatively (15 and 29 mmoL, respectively). Postoperatively, two other patients of Group A received 19 and 12,5 mmoL, respectively, and one of Group B received 20 mmoL potassium. CONCLUSIONS: Both regimens resulted in relatively stable and comparable blood glucose levels throughout the perioperative period of the minor and major surgeries without differences in metabolic control as measured by levels of lactate, cortisol, glycerol and free fatty acids. Simplicity would favor the intermittent regimen to manage insulin treated type 2 diabetics.

Phylogeny of all recognized species of ammonia oxidizers based on comparative 16S rRNA and amoA sequence analysis: implications for molecular diversity surveys.

The current perception of evolutionary relationships and the natural diversity of ammonia-oxidizing bacteria (AOB) is mainly based on comparative sequence analyses of their genes encoding the 16S rRNA and the active site polypeptide of the ammonia monooxygenase (AmoA). However, only partial 16S rRNA sequences are available for many AOB species and most AOB have not yet been analyzed on the amoA level. In this study, the 16S rDNA sequence data of 10 Nitrosomonas species and Nitrosococcus mobilis were completed. Furthermore, previously unavailable 16S rRNA sequences were determined for three Nitrosomonas sp. isolates and for the gamma-subclass proteobacterium Nitrosococcus halophilus. These data were used to revaluate the specificities of published oligonucleotide primers and probes for AOB. In addition, partial amoA sequences of 17 AOB, including the above-mentioned 15 AOB, were obtained. Comparative phylogenetic analyses suggested similar but not identical evolutionary relationships of AOB by using 16S rRNA and AmoA as marker molecules, respectively. The presented 16S rRNA and amoA and AmoA sequence data from all recognized AOB species significantly extend the currently used molecular classification schemes for AOB and now provide a more robust phylogenetic framework for molecular diversity inventories of AOB. For 16S rRNA-independent evaluation of AOB species-level diversity in environmental samples, amoA and AmoA sequence similarity threshold values were determined which can be used to tentatively identify novel species based on cloned amoA sequences. Subsequently, 122 amoA sequences were obtained from 11 nitrifying wastewater treatment plants. Phylogenetic analyses of the molecular isolates showed that in all but two plants only nitrosomonads could be detected. Although several of the obtained amoA sequences were only relatively distantly related to known AOB, none of these sequences unequivocally suggested the existence of previously unrecognized species in the wastewater treatment environments examined.