Fibroblast growth factor receptor 4 single nucleotide polymorphism Gly388Arg in head and neck carcinomas

BACKGROUND Head and neck squamous cell carcinoma (HNSCC) is considered to be a progressive disease resulting from alterations in multiple genes regulating cell proliferation and differentiation like receptor tyrosine kinases (RTKs) and members of the fibroblast growth factor receptors (FGFR)-family. Single-nucleotide polymorphism (SNP) Arg388 of the FGFR4 is associated with a reduced overall survival in patients with cancers of various types. We speculate that FGFR4 expression and SNP is associated with worse survival in patients with HSNCC. AIM To investigate the potential clinical significance of FGFR4 Arg388 in the context of tumors arising in HNSCC, a comprehensive analysis of FGFR4 receptor expression and genotype in tumor tissues and correlated results with patients' clinical data in a large cohort of patients with HNSCC was conducted. METHODS Surgical specimens from 284 patients with HNSCC were retrieved from the Institute of Pathology at the Ludwig-Maximilian-University in Germany. Specimens were analyzed using immunohistochemistry and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The expression of FGFR4 was analyzed in 284 surgical specimens of HNSCC using immunohistochemstry. FGFR4 polymorphism was detected by PCR-RFLP. Patients' clinical data with a minimum follow-up of 5 syears were statistically evaluated with a special emphasis on survival analysis employing Kaplan-Meier estimator and Cox regression analysis. RESULTS Concerning the invasive tumor areas the intensity of the FGFR4 expression was evaluated in a four-grade system: no expression, low expression, intermediate and high expression. FGFR4 expression was scored as "high" (+++) in 74 (26%), "intermediate" (++) in 103 (36.3%), and "low" (+) in 107 (36.7%) cases. Analyzing the FGFR4 mutation it was found in 96 tumors (33.8%), 84 of them (29.6%) having a heterozygous and 12 (4.2%) homozygous mutated Arg388 allele. The overall frequency concerning the mutant alleles demonstrated 65% vs 34% mutated alleles in general. FGFR4 Arg388 was significantly associated with advanced tumor stage (P < 0.004), local metastasis (P < 0.0001) and reduced disease-free survival (P < 0.01). Furthermore, increased expression of FGFR4 correlated significantly with worse overall survival (P < 0.003). CONCLUSION In conclusion, the FGFR4 Arg388 genotype and protein expression of FGFR4 impacts tumor progression in patients with HNSCC and may present a useful target within a multimodal therapeutic intervention

Liquid chromatography-tandem mass spectrometry - Application in the clinical laboratory

This review provides a concise survey of liquid chromatography tandem mass spectrometry (LCTMS) as an emerging technology in clinical chemistry. The combination of two mass spectrometers with an interposed collision cell characterizes LCTMS as an analytical technology on its own and not just as a more specific detector for HPLC compared with conventional techniques. In LCTMS, liquid chromatography is rather used for sample preparation but not for complete resolution of compounds of interest. The instrument technology of LCTMS is complex and comparatively expensive; however, in routine use, methods are far more rugged compared to conventional chromatographic techniques and enable highthroughput analyses with very limited manual handling steps. Moreover, compared to both gas chromatographymass spectrometry (GCMS) and conventional HPLC techniques, LCTMS is substantially more versatile with respect to the spectrum of analyzable compounds. For these reasons it is likely that LCTMS will gain far more widespread use in the clinical laboratory than HPLC and GCMS ever did. In this article, the key features of LCTMS are described, method development is explained, typical fields of application are discussed, and personal experiences are related

No-Tillage in Europe - State of the Art: Constraints and Perspectives

No-tillage in Europe contains a review of developments over the last three decades beginning in the late 1960s. Reasons for attempts to introduce this soil conserving production method are outlined and obstacles affecting the uptake of no-tillage throughout Europe are identified. Updated data are provided for the uptake of both conservation tillage and no-tillage in the member countries of the European Conservation Agriculture Federation. Further explanations for the low uptake of no-tillage and even conservation tillage when compared to other regions in the world are explored. The specificity of European conditions whether natural, human or political are used to provide arguments against the successful adoption of no-tillage in Europe. However, increased awareness of farmers, politicians and society as a whole that soils are a non-renewable resource are leading to gradual changes in the overall approach to soil conservation. The implementation of a European Soil Framework Directive is considered to be an important step towards the recognition that conservation tillage and no-tillage is both an economical and ecological sustainable method for crop production. It is anticipated that this will promote the concept of Conservation Agriculture and increase adoption levels throughout Europe

Microglia and neuroinflammation: a pathological perspective

Microglia make up the innate immune system of the central nervous system and are key cellular mediators of neuroinflammatory processes. Their role in central nervous system diseases, including infections, is discussed in terms of a participation in both acute and chronic neuroinflammatory responses. Specific reference is made also to their involvement in Alzheimer's disease where microglial cell activation is thought to be critically important in the neurodegenerative process

Nitrogen fixation in sediments along a depth transect through the Peruvian oxygen minimum zone

Benthic nitrogen (N2) fixation and sulfate reduction (SR) were investigated in the Peruvian oxygen minimum zone (OMZ). Sediment samples, retrieved by a multiple corer were taken at six stations (70–1025 m) along a depth transect at 12° S, covering anoxic and hypoxic bottom water conditions. Benthic N2 fixation was detected at all sites, with high rates measured in OMZ mid-waters between the 70 and 253 m and lowest N2 fixation rates below 253 m down to 1025 m water depth. SR rates were decreasing with increasing water depth, with highest rates at the shallow site. Benthic N2 fixation depth profiles largely overlapped with SR depth profiles, suggesting that both processes are coupled. The potential of N2 fixation by SR bacteria was verified by the molecular analysis of nifH genes. Detected nifH sequences clustered with SR bacteria that have been demonstrated to fix N2 in other benthic environments. Depth-integrated rates of N2 fixation and SR showed no direct correlation along the 12° S transect, suggesting that the benthic diazotrophs in the Peruvian OMZ are being controlled by additional various environmental factors. The organic matter availability and the presence of sulfide appear to be major drivers for benthic diazotrophy. It was further found that N2 fixation was not inhibited by high ammonium concentrations. N2 fixation rates in OMZ sediments were similar to rates measured in other organic-rich sediments. Overall, this work improves our knowledge on N sources in marine sediments and contributes to a better understanding of N cycling in OMZ sediments

Novel biocatalysts by identification and design

Enzymes produced from bacteria and eukaryotic organisms are presently being used for a large variety of different biotechnological applications. The rapidly increasing demand for enzymes which are active towards novel and often non-natural substrates has triggered the development of novel molecular biological methods of enzyme isolation and design. The metagenome approach is a cultivation-independent method which allows the direct cloning and expression of environmental DNA thereby providing access to a wealth of so-far unknown biocatalysts. Additionally, newly identified or existing biocatalysts can be further optimized by different methods of directed evolution. Here, the principle of the metagenome approach is outlined and a strategy is presented for the optimization of a bacterial lipase using a combination of rational design and directed evolution.

Competitiveness and communication for effective inoculation byRhizobium, Bradyrhizobium and vesicular-arbuscular mycorrhiza fungi

After a short summary on the ecology and rhizosphere biology of symbiotic bacteria and vesicular-arbuscular (VA) mycorrhiza fungi and their application as microbial inocula, results on competitiveness and communication are summarized. Stress factors such as high temperature, low soil pH, aluminium concentrations and phytoalexins produced by the host plants were studied withRhizobium leguminosarum bv.phaseoli andRhizobium tropici onPhaseolus beans. Quantitative data for competitiveness were obtained by usinggus + (glucoronidase) labelled strains, which produce blue-coloured nodules. ForPhaseolus-nodulating rhizobia, a group specific DNA probe was also developed, which did not hybridize with more than 20 other common soil and rhizosphere bacteria. Results from several laboratories contributing to knowledge of signal exchange and communication in theRhizobium/Bradyrhizobium legume system are summarized in a new scheme, including also defense reactions at the early stages of legume nodule initiation. Stimulating effects of flavonoids on germination and growth of VA mycorrhiza fungi were also found. A constitutive antifungal compound in pea roots, -isoxazolinonyl-alanine, was characterized

Cortical hypertrophy with a short, curved uncemented hip stem does not have any clinical impact during early follow-up

Background: Short stems have become more and more popular for cementless total hip arthroplasty in the past few years. While conventional, uncemented straight stems for primary total hip arthroplasty (THA) have shown high survival rates in the long term, it is not known whether uncemented short stems represent a reasonable alternative. As cortical hypertrophy has been reported for short stems, the aim of this study was to determine the radiographic prevalence of cortical hypertrophy and to assess the clinical outcome of a frequently used short, curved hip stem. Methods: We retrospectively studied the clinical and radiographic results of our first 100 consecutive THAs (97 patients) using the Fitmore® hip stem. Mean age at the time of index arthroplasty was 59 years (range, 19 – 79 years). Clinical outcome and radiographic results were assessed with a minimum follow-up of 2 years, and Kaplan-Meier survivorship analysis was used to estimate survival for different endpoints. Results: After a mean follow-up of 3.3 years (range, 2.0 – 4.4 years), two patients (two hips) had died, and three patients (four hips) were lost to follow-up. Kaplan-Meier analysis estimated a survival rate of 100 % at 3.8 years, with revision for any reason as the endpoint. No femoral component showed radiographic signs of loosening. No osteolysis was detected. Cortical hypertrophy was found in 50 hips (63 %), predominantly in Gruen zone 3 and 5. In the cortical hypertrophy group, two patients (two hips; 4 %) reported some thigh pain in combination with pain over the greater trochanter region during physical exercise (UCLA Score 6 and 7). There was no significant difference concerning the clinical outcome between the cortical hypertrophy and no cortical hypertrophy group. Conclusions: The survival rate and both clinical and the radiographic outcome confirm the encouraging results for short, curved uncemented stems. Postoperative radiographs frequently displayed cortical hypertrophy but it had no significant effect on the clinical outcome in the early follow-up. Further clinical and radiographic follow-up is necessary to detect possible adverse, long-term, clinical effects of cortical hypertrophy