bluuebunny/crossref_metadata_2025 huggingface dataset:
Eosinophils and Oral Squamous Cell Carcinoma: A Short Review
Authors: Martinelli-Kläy C. P. , Mendis B. R. R. N. , Lombardi T.
Published: December 2009

The eosinophil cell has been related as a prognostic indicator for cancers. However, its exact function in tumour behaviour is still not clearly defined. In the oral cavity the presence of eosinophils can be a favourable prognostic indicator as well as it may be associated with a poor prognosis. In this short review, we briefly summarize the role of the eosinophils in the general context of immunoregulation and its relation to oral squamous cell carcinoma.
A Modal‐Based Substructure Method Applied to Nonlinear Rotordynamic Systems
Authors: Holl Helmut J.
Published: December 2009

The discretisation of rotordynamic systems usually results in a high number of coordinates, so the computation of the solution of the equations of motion is very time consuming. An efficient semianalytic time‐integration method combined with a substructure technique is given, which accounts for nonsymmetric matrices and local nonlinearities. The partitioning of the equation of motion into two substructures is performed. Symmetric and linear background systems are defined for each substructure. The excitation of the substructure comes from the given excitation force, the nonlinear restoring force, the induced force due to the gyroscopic and circulatory effects of the substructure under consideration and the coupling force of the substructures. The high effort for the analysis with complex numbers, which is necessary for nonsymmetric systems, is omitted. The solution is computed by means of an integral formulation. A suitable approximation for the unknown coordinates, which are involved in the coupling forces, has to be introduced and the integration results in Green′s functions of the considered substructures. Modal analysis is performed for each linear and symmetric background system of the substructure. Modal reduction can be easily incorporated and the solution is calculated iteratively. The numerical behaviour of the algorithm is discussed and compared to other approximate methods of nonlinear structural dynamics for a benchmark problem and a representative example.
A Galerkin‐Parameterization Method for the Optimal Control of Smart Microbeams
Authors: Abukhaled Marwan , Sadek Ibrahim
Published: December 2009

A proposed computational method is applied to damp out the excess vibrations in smart microbeams, where the control action is implemented using piezoceramic actuators. From a mathematical point of view, we wish to determine the optimal boundary actuators that minimize a given energy‐based performance measure. The minimization of the performance measure over the actuators is subjected to the full motion of the structural vibrations of the micro‐beams. A direct state‐control parametrization approach is proposed where the shifted Legendre polynomials are employed to solve the optimization problem. Legendre operational matrix and the properties of Kronecker product are utilized to find the approximated optimal trajectory and optimal control law of the lumped parameter systems with respect to the quadratic cost function by solving linear algebraic equations. Numerical examples are provided to demonstrate the applicability and efficiency of the proposed approach.
A New Iteration Process for Approximation of Common Fixed Points for Finite Families of Total Asymptotically Nonexpansive Mappings
Authors: Chidume C. E. , Ofoedu E. U.
Published: December 2009

Let E be a real Banach space, and K a closed convex nonempty subset of E.
Let T1, T2, …, Tm : K → K be m total asymptotically nonexpansive mappings. A
simple iterative sequence is constructed in E and necessary and sufficient
conditions for this sequence to converge to a common fixed point of are given. Furthermore, in the case that E is a uniformly convex real Banach space,
strong convergence of the sequence to a common fixed point of the family
is proved. Our recursion formula is much simpler and much more applicable than those recently announced by several authors for the same problem.
Laparoscopic Distal Pancreatectomy with Splenic Conservation: An Operation without Increased Morbidity
Authors: Nau Peter , Melvin W. Scott , Narula Vimal K. , Bloomston P. Mark , Ellison E. Christopher , Muscarella Peter
Published: December 2009

Objectives. The advent of minimally invasive techniques was marked by a paradigm shift towards the use of laparoscopy for benign distal pancreatic masses. Herein we describe one center's experience with laparoscopic distal pancreatectomy.Methods. A retrospective chart review was performed for all distal pancreatectomies completed laparoscopically from 1999 to 2009. Outcomes from those cases completed with a concurrent splenectomy were compared to the spleen-preserving procedures.Results. Twenty-four patients underwent laparoscopic distal pancreatectomy. Seven had spleen-conserving operations. There was no difference in the mean estimated blood loss (316 versus 285 mL, ) or operative time (179 versus 170 minutes, ). The mean tumor size was not significantly different (3.1 versus 2.2 cm, ). There was no difference in the average hospital stay (7.1 versus 7.0 days, ). Complications in the spleen-preserving group included one iatrogenic colon injury, two pancreatic fistulas, and two cases of iatrogenic diabetes. In the splenectomy group, two developed respiratory failure, three acquired iatrogenic diabetes, and two suffered pancreatic fistulas (71% versus 41% , ).Conclusions. The laparoscopic distal pancreatectomy is a safe operation with a low morbidity. Splenic conservation does not significantly increase the morbidity of the procedure.
How Fast Is the Sessile Ciona?
Authors: Berná Luisa , Alvarez-Valin Fernando , D'Onofrio Giuseppe
Published: December 2009

Genomewide analyses of distances between orthologous gene pairs from the ascidian speciesCiona intestinalisandCiona savignyiwere compared with those of vertebrates. Combining this data with a detailed and careful use of vertebrate fossil records, we estimated the time of divergence between the two ascidians nearly 180 My. This estimation was obtained after correcting for the different substitution rates found comparing several groups of chordates; indeed we determine here that on average Ciona species evolve 50% faster than vertebrates.
The Emerging Role of PARP Inhibitors in the Treatment of Epithelial Ovarian Cancer
Authors: Gien Lilian T. , Mackay Helen J.
Published: December 2009

Poly(ADP-ribose) polymerase-1 (PARP-1) is an important novel target in cancer therapy. This enzyme is essential in the repair of single-stranded breaks in DNA via the base excision repair pathway. Drugs which inhibit PARP are emerging as a promising new class of anticancer agents particularly effective against tumors which have lost homologous recombination (HR) through loss of functional BRCA1 and BRCA2. PARP inhibitors potentially represent a major breakthrough for patients with hereditary BRCA-associated cancers. Furthermore their role in sporadic epithelial ovarian cancer is emerging with identification of additional subpopulations of women who may benefit a priority. This paper will summarize the mechanism of action of PARP inhibition and its role in the treatment of BRCA1- and 2-associated cancers. We will then expand on the broader relevance and future directions for PARP inhibition in the clinical setting.
Adaptive Fuzzy Tracking Control for a Permanent Magnet Synchronous Motor via Backstepping Approach
Authors: Yu Jinpeng , Gao Junwei , Ma Yumei , Yu Haisheng
Published: December 2009

The speed tracking control problem of permanent magnet synchronous motors
with parameter uncertainties and load torque disturbance is addressed. Fuzzy
logic systems are used to approximate nonlinearities, and an adaptive
backstepping technique is employed to construct controllers. The proposed
controller guarantees the tracking error convergence to a small neighborhood of
the origin and achieves the good tracking performance. Simulation results
clearly show that the proposed control scheme can track the position
reference signal generated by a reference model successfully under parameter
uncertainties and load torque disturbance without singularity and
overparameterization.
Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers
Authors: Cochrane Dawn R. , Howe Erin N. , Spoelstra Nicole S. , Richer Jennifer K.
Published: December 2009

We focus on unique roles of miR-200c in breast, ovarian, and endometrial cancers. Members of the miR-200 family target ZEB1, a transcription factor which represses E-cadherin and other genes involved in polarity. We demonstrate that the double negative feedback loop between miR-200c and ZEB1 is functional in some, but not all cell lines. Restoration of miR-200c to aggressive cancer cells causes a decrease in migration and invasion. These effects are independent of E-cadherin status. Additionally, we observe that restoration of miR-200c to ovarian cancer cells causes a decrease in adhesion to laminin. We have previously reported that reintroduction of miR-200c to aggressive cells that lack miR-200c expression restores sensitivity to paclitaxel. We now prove that this ability is a result of direct targeting of class III beta-tubulin (TUBB3). Introduction of a TUBB3 expression construct lacking the miR-200c target site into cells transfected with miR-200c mimic results in no change in sensitivity to paclitaxel. Lastly, we observe a decrease in proliferation in cells transfected with miR-200c mimic, and cells where ZEB1 is knocked down stably, demonstrating that the ability of miR-200c to enhance sensitivity to paclitaxel is not due to an increased proliferation rate.
The Second Eigenvalue of the p‐Laplacian as p Goes to 1
Authors: Parini Enea
Published: December 2009

The asymptotic behaviour of the second eigenvalue of the p‐Laplacian operator as p goes to 1 is investigated. The limit setting depends only on the geometry of the domain. In the particular case of a planar disc, it is possible to show that the second eigenfunctions are nonradial if p is close enough to 1.
Overexpression of Phospho-eIF4E Is Associated with Survival through AKT Pathway in Non–Small Cell Lung Cancer
Authors: Yoshizawa Akihiko , Fukuoka Junya , Shimizu Shigeki , Shilo Konstantin , Franks Teri J. , Hewitt Stephen M. , Fujii Takeshi , Cordon-Cardo Carlos , Jen Jin , Travis William D.
Published: December 2009

Purpose: The eukaryotic translation initiation factor complex 4E (eIF4E) is downstream in the mammalian target of rapamycin (mTOR) pathway. This study explored expression of eIF4E and its relationship with the PTEN/AKT and RAS/MEK/ERK pathways in non–small cell lung carcinoma (NSCLC).

Experimental Design: The status of phosphorylated eIF4E (p-eIF4E), phosphorylated AKT (p-AKT), PTEN, phosphorylated tuberin (p-TSC2), phosphorylated mTOR (p-mTOR), phosphorylated S6 (p-S6), and phosphorylated Erk1/2 (p-Erk1/2) was studied using immunohistochemical analysis applied to a tissue microarray containing 300 NSCLCs. Staining results for each antibody were compared with clinical and pathologic features, and the relationship between staining results was explored.

Results: Overexpression of p-eIF4E, p-AKT, p-TSC2, p-mTOR, p-S6, and p-Erk1/2 in NSCLC was found in 39.9%, 78.8%, 5.1%, 46.7%, 27.1%, and 16.6% of tumors, respectively. The phenotype of p-eIF4E correlated positively with that of p-AKT, p-TSC2, and p-S6 (P < 0.001). Overall survival in NSCLC patients was significantly shorter in cases with overexpression of p-eIF4E and p-AKT alone and in combination (log-rank P < 0.001, each). Cases with underexpression of PTEN were limited (6.4%), and this phenotype did not correlate with any clinical variable. In cluster analysis, the p-AKT/p-mTOR/p-eIF4E/p-S6–positive group had significantly shorter survival compared with the survival of all cases (P < 0.001). Multivariate analysis showed that p-eIF4E overexpression is an independent prognostic factor for NSCLC (P = 0.004).

Conclusions: This study shows that p-eIF4E expression in addition to p-AKT predicts poor prognosis in NSCLC. Moreover, the correlation between expression of p-eIF4E with p-AKT, as well as p-TSC2 and p-S6, indicates that eIF4E activation through the AKT pathway plays an important role in the progression of NSCLC. Clin Cancer Res; 16(1); OF1–9
Exposure of Intestinal Epithelial Cells to UV-Killed Lactobacillus GG but Not Bifidobacterium breve Enhances the Effector Immune Response in vitro
Authors: van Hoffen Els , Korthagen Nicoline M. , de Kivit Sander , Schouten Bastiaan , Bardoel Bart , Duivelshof Arjan , Knol Jan , Garssen Johan , Willemsen Linette E.M.
Published: December 2009

Background: Intestinal bacteria and intestinal epithelial cells (IEC) may modulate the mucosal immune response. In this study, immune modulation by Lactobacillus GG (LGG) and Bifidobacterium breve (Bb1, Bb2) in the presence or absence of IEC was addressed in an in vitro transwell co-culture model. Methods: UV-killed LGG,Bb1, Bb2 or Toll-like receptor (TLR) 2 or nucleotide oligomerization domain (NOD) 2 ligands were added directly to unstimulated or anti-CD3/CD28-stimulated PBMC, or applied apically to human IEC (HT-29) co-cultured with PBMC. A mixture of live bacteria was used as reference. The effect on T helper 1 (IFN-γ, IL-12), T helper 2 (IL-13), inflammatory (TNF-α) and regulatory (IL-10) cytokine secretion was determined. Results: Both UV-killed LGG and Bb enhanced IL-12, IFN-γ, TNF-α and IL-10, and reduced IL-13 secretion when added directly to stimulated PBMC, similar to live bacteria. IEC reduced IL-13, IFN-γ and IL-10 secretion by stimulated PBMC. Apically added LGG, TLR2 and NOD2 ligands,but not Bb, enhanced IFN-γ, IL-12 and/or TNF-α secretion. Bacteria did not induce cytokine secretion when added to HT-29/unstimulated PBMC co-cultures, whereas direct incubations with PBMC did. Conclusion: UV-killed LGG as well as Bb supported a T helper 1 and/or regulatory phenotype when added directly to activated PBMC, similar to live bacteria. In contrast, LGG, TLR2 or NOD2 ligands – but not Bb – enhanced T helper 1 type cytokine secretion when added to IEC, while IL-10 secretion remained suppressed. Co-cultures combining IEC and PBMC may reveal differences between bacterial strains relevant for the in vivo situation.
The Diabetic Antigen Glutamic Acid Decarboxylase (GAD 65) in the Human Peripheral Blood
Authors: Tilz G.P. , Dausset J. , Wiltgen M.
Published: December 2009

Background: Glutamic acid decarboxylase (GAD 65) is a diabetes-associated antigen which is generally considered to be strictly intracellular. In order to better understand autoimmunity, this study demonstrates the appearance of GAD 65 in the peripheral human blood and presents implications for the diagnosis and therapy of some autoimmune diseases. Methods: The GAD 65 molecules are detected by their interaction with monoclonal antibodies labeled with dyes in an experimental setup with fluorescence correlation spectroscopy (FCS). These interactions result in changes in Brownian motion measured as fluorescence fluctuations. Sera from 153 patients with diabetes mellitus type 1 and controls were investigated. To enable the representation of the molecule as a model for further discussions, we present structural visualizations of its hydrophobic properties, leading to possible interactions with the cell membrane lipids and epitope locations. Results: The GAD65 antigen could be measured with a sensitivity of 2.65 µg/ml in ‘clean systems’ resulting from spiking experiments and human sera. The GAD 65 antigen could be identified in 8 patient sera: 4 children with diabetes mellitus type 1 and 4 adults initially taken as controls but who retrospectively showed signs of autoimmunity. Conclusion: We conclude that these findings are of significance for the concept of autoimmunity, i.e. in an initial step the immune system is primed by its accessibility to GAD 65. Our experimental results may also be important for the therapy of diabetes mellitus type 1 and other autoimmune diseases by the passive administration of GAD 65 antibodies.
Stainless Steel Ions Stimulate Increased Thrombospondin-1-Dependent TGF-Beta Activation by Vascular Smooth Muscle Cells: Implications for In-Stent Restenosis
Authors: Pallero Manuel A. , Talbert Roden Melissa , Chen Yiu-Fai , Anderson Peter G. , Lemons Jack , Brott Brigitta C. , Murphy-Ullrich Joanne E.
Published: December 2009

Background/Aims: Despite advances in stent design, in-stent restenosis (ISR) remains a significant clinical problem. All implant metals exhibit corrosion, which results in release of metal ions. Stainless steel (SS), a metal alloy widely used in stents, releases ions to the vessel wall and induces reactive oxygen species, inflammation and fibroproliferative responses. The molecular mechanisms are unknown. TGF-β is known to be involved in the fibroproliferative responses of vascular smooth muscle cells (VSMCs) in restenosis, and TGF-β antagonists attenuate ISR. We hypothesized that SS ions induce the latent TGF-β activator, thrombospondin-1 (TSP1), through altered oxidative signaling to stimulate increased TGF-β activation and VSMC phenotype change. Methods: VSMCs were treated with SS metal ion cocktails, and morphology, TSP1, extracellular matrix production, desmin and TGF-β activity were assessed by immunoblotting. Results: SS ions stimulate the synthetic phenotype, increased TGF-β activity, TSP1, increased extracellular matrix and downregulation of desmin in VSMCs. Furthermore, SS ions increase hydrogen peroxide and decrease cGMP-dependent protein kinase (PKG) signaling, a known repressor of TSP1 transcription. Catalase blocks SS ion attenuation of PKG signaling and increased TSP1 expression. Conclusions: These data suggest that ions from stent alloy corrosion contribute to ISR through stimulation of TSP1-dependent TGF-β activation.
Thrombus versus Wall Biological Activities in Experimental Aortic Aneurysms
Authors: Coutard Michèle , Touat Ziad , Houard Xavier , Leclercq Anne , Michel Jean-Baptiste
Published: December 2009

Background/Aim: The intraluminal thrombus (ILT) is considered to participate in abdominal aortic aneurysm (AAA) evolution. To assess whether this role proceeds via ILT influence on biological activity of the AAA wall, we studied the relationships between the levels of some relevant proteases and microparticles (MP) released by ILT versus wall in rat experimental AAAs. Methods and Results: Two weeks after elastase perfusion, ILT and AAA wall were incubated in cell culture medium and studies were performed on conditioned media. As shown by gelatin zymography, ILT released higher amounts of MMP9 than the wall, whereas the level of MMP2 activation (active/pro) was similar. Levels of elastase and urokinase plasminogen activator, plasmin and MPs, determined, respectively, by casein zymography, substrate hydrolysis and flow cytometry, were higher in ILT than in wall. Aneurysm diameter positively correlated with wall MMP9 levels, MMP2 activation, plasmin activity and MP release. Moreover, wall and ILT levels of pro- and active forms of MMP2, elastase and plasmin were positively correlated. Wall levels of MMP2 activation and plasmin activity also correlated with ILT weight. Conclusion: The present data suggest that, in this experimental model, ILT may contribute to AAA evolution via its influence on the level of aneurysmal wall protease activity.
Toll-Like Receptor Responses in IRAK-4-Deficient Neutrophils
Authors: van Bruggen Robin , Drewniak Agata , Tool Anton T.J. , Jansen Machiel , van Houdt Michel , Geissler Judy , van den Berg Timo K. , Chapel Helen , Kuijpers Taco W.
Published: December 2009

Human neutrophils were found to express all known Toll-like receptors (TLRs) except TLR3 and TLR7. IRAK-4-deficient neutrophils were tested for their responsiveness to various TLR ligands. Essentially all TLR responses in neutrophils, including the induction of reactive oxygen species generation, adhesion, chemotaxis and IL-8 secretion, were found to be dependent on IRAK-4. Surprisingly, the reactivity towards certain established TLR ligands, imiquimod and ODN-CpG, was unaffected by IRAK-4 deficiency, demonstrating their activity is independent of TLR. TLR-4-dependent signaling in neutrophils was totally dependent on IRAK-4 without any major TRIF-mediated contribution. We did not observe any defects in killing capacity of IRAK-4-deficient neutrophils for Staphylococcus aureus, Escherichia coli and Candida albicans, suggesting that microbial killing is primarily TLR independent.
Testing the Moderating Role of the Components of Norm Activation on the Relationship Between Values and Environmental Behavior
Authors: Milfont Taciano L. , Sibley Chris G. , Duckitt John
Published: December 2009

This study replicates and expands Schultz et al.’s findings regarding the applicability of the norm-activation model on self-reported environmental behavior. As expected, a significant three-way interaction was found among perceived seriousness of global environmental problems, ascription of responsibility for global environmental problems, and altruistic values when predicting environmental behaviors. This held even considering smaller measures, an online procedure to gather data, a diverse sample from more than 50 countries, and controlling for content overlap between measures.
Regulatory Accessibility and Social Influences on State Self-Control
Authors: vanDellen Michelle R. , Hoyle Rick H.
Published: December 2009

The current work examined how social factors influence self-control. Current conceptions of state self-control treat it largely as a function of regulatory capacity. The authors propose that state self-control might also be influenced by social factors because of regulatory accessibility. Studies 1 through 4 provide evidence that individuals’ state self-control is influenced by the trait and state self-control of salient others such that thinking of others with good trait or state self-control leads to increases in state self-control and thinking of others with bad trait or state self-control leads to decreases in state self-control. Study 5 provides evidence that the salience of significant others influences both regulatory accessibility and state self-control. Combined, these studies suggest that the effects of social influences on state self-control occur through multiple mechanisms.
From Opinion-Based to Evidence-Based Social Work: The Swedish Case
Authors: Sundell Knut , Soydan Haluk , Tengvald Karin , Anttila Sten
Published: December 2009

This article presents an account of Sweden’s Institute for Evidence-Based Social Work Practice (IMS), located in Stockholm, Sweden. The article places IMS in the context of making Swedish social care services less opinion-based and more evidence-based. The institute is an example of how policy-driven processes promote the use of evidence-based practices in this European nation. The article includes presentations of history, organization, and products of IMS, and concludes with comments on future opportunities and challenges.
Continuous Deep Sedation Until Death: Palliation or Physician-Assisted Death?
Authors: Rady Mohamed Y. , Verheijde Joseph L.
Published: December 2009

Published literature have not discerned end-of-life palliative versus life-shortening effects of pharmacologically maintaining continuous deep sedation until death (ie, dying in deep sleep) compared with common sedation practices relieving distress in the final conscious phase of dying. Continuous deep sedation predictably suppresses brainstem vital centers and shortens life. Continuous deep sedation remains controversial as palliation for existential suffering and in elective death requests by discontinuation of chronic ventilation or circulatory support with mechanical devices. Continuous deep sedation contravenes the double-effect principle because: (1) it induces permanent coma (intent of action) for the contingency relief of suffering and for social isolation (desired outcomes) and (2) because of its predictable and proportional life-shortening effect. Continuous deep sedation should be distinguished from common sedation practices for palliation and characterized instead as physician-assisted death.
Stereotype Threat, State Anxiety, and Specific Self-Efficacy as Predictors of Promotion Exam Performance
Authors: Chung Beth G. , Ehrhart Mark G. , Holcombe Ehrhart Karen , Hattrup Keith , Solamon Jerry
Published: December 2009

This field study examined perceived stereotype threat in a promotion context using a written job knowledge test. The authors hypothesized that race and ethnic identity would predict perceptions of stereotype threat and that the effect of stereotype threat on test performance would be mediated by state anxiety and specific self-efficacy in a specified sequential order. Using structural equation modeling analyses of data from two public safety departments in a metropolitan city indicated support for this model. However, the stereotype threat effect was small, which may be because of the use of a job knowledge test, a promotion sample, or the composition of the applicant pool. Noteworthy contributions include the use of a self-report measure of stereotype threat, inclusion of two mediator variables in a theory-based sequence, and a test of the stereotype threat effect in an actual employment context.
Effects of Dance on Gait and Balance in Parkinson’s Disease: A Comparison of Partnered and Nonpartnered Dance Movement
Authors: Hackney Madeleine E. , Earhart Gammon M.
Published: December 2009

Partnered tango dance can improve balance and gait in individuals with Parkinson’s disease (PD). Partnered dance may allow these individuals to challenge balance more than nonpartnered dance. Alternatively, partnered practice could reduce balance gains because the participant may rely on the partner as a balance aid when challenged. The authors compared the effects of partnered and nonpartnered dance on balance and mobility in 39 people (11 women) with mild-moderate PD (Hoehn and Yahr stages I-III). Participants were randomly assigned to partnered or nonpartnered tango and attended 1-hour classes twice per week, completing 20 lessons within 10 weeks. Balance and gait were evaluated in the weeks immediately before, immediately after, and 1 month after the intervention. Both groups significantly improved on the Berg Balance Scale, comfortable and fast-as-possible walking velocity, and cadence. Improvements were maintained at the 1-month follow-up. The nonpartnered class improved as much as the partnered class; however, partnered participants expressed more enjoyment and interest in continuing.
Achilles Tendon Rupture
Authors: Hess Gregory William
Published: December 2009

Sports participation has undergone an increase in recent decades. Injury due to sporting activity has also recently risen. The Achilles tendon has been one of the most common sports-related injuries. A 2 in 100 000 individual Achilles tendon injury rate increased to a 12 in 100 000 individual injury rate in less than 10 years. The injury is typically observed in men in the fourth to fifth decades of life. Male to female injury ratios range from 2:1 to 12:1. Running, jumping, and agility activities involving eccentric loading and explosive plyometric contractions are usual mechanisms. Natural aging allows predisposing chronic degeneration of the tendon. Blood flow decreases and stiffness increases with aging to decrease the ability to withstand stress. Noninflammatory tendinosis and chronic tendinopathy are 2 separate processes proposed for tendon degeneration and subsequent rupture. Rupture typically occurs 2 to 6 cm proximal to the calcaneal insertion. Predisposing factors are grouped into 2 categories: intrinsic and extrinsic risk factors. Avoidance of degenerative changes within the tendon is the primary method to prevent rupture. Regular physical activity as athletes age also promotes tendon hypertrophy, increases nutrient delivery, and reduces collagen fiber fatigue.
How I treat influenza in patients with hematologic malignancies
Authors: Casper Corey , Englund Janet , Boeckh Michael
Published: December 2009

The 2009 H1N1 influenza pandemic has heightened the interest of clinicians for options in the prevention and management of influenza virus infection in immunocompromised patients. Even before the emergence of the novel 2009 H1N1 strain, influenza disease was a serious complication in patients with hematologic malignancies receiving chemotherapy or undergoing hematopoietic cell transplantation. Here we review the clinical manifestations of seasonal and 2009 H1N1 influenza and discuss current diagnosis, antiviral treatment, and prophylaxis options. We also summarize infection control and vaccination strategies for patients, family members, and caregivers.
Analysis of replication factories in human cells by super-resolution light microscopy
Authors: Cseresnyes Zoltan , Schwarz Ulf , Green Catherine M
Published: December 2009

Background

DNA replication in human cells is performed in discrete sub-nuclear locations known as replication foci or factories. These factories form in the nucleus during S phase and are sites of DNA synthesis and high local concentrations of enzymes required for chromatin replication. Why these structures are required, and how they are organised internally has yet to be identified. It has been difficult to analyse the structure of these factories as they are small in size and thus below the resolution limit of the standard confocal microscope. We have used stimulated emission depletion (STED) microscopy, which improves on the resolving power of the confocal microscope, to probe the structure of these factories at sub-diffraction limit resolution.

Results

Using immunofluorescent imaging of PCNA (proliferating cell nuclear antigen) and RPA (replication protein A) we show that factories are smaller in size (approximately 150 nm diameter), and greater in number (up to 1400 in an early S- phase nucleus), than is determined by confocal imaging. The replication inhibitor hydroxyurea caused an approximately 40% reduction in number and a 30% increase in diameter of replication factories, changes that were not clearly identified by standard confocal imaging.

Conclusions

These measurements for replication factory size now approach the dimensions suggested by electron microscopy. This agreement between these two methods, that use very different sample preparation and imaging conditions, suggests that we have arrived at a true measurement for the size of these structures. The number of individual factories present in a single nucleus that we measure using this system is greater than has been previously reported. This analysis therefore suggests that each replication factory contains fewer active replication forks than previously envisaged.
Increased epithelial stem cell traits in advanced endometrial endometrioid carcinoma
Authors: Chang Shing-Jyh , Wang Tao-Yeuan , Tsai Chan-Yen , Hu Tzu-Fang , Chang Margaret Dah-Tsyr , Wang Hsei-Wei
Published: December 2009

Background

It has been recognized cancer cells acquire characters reminiscent of those of normal stem cells, and the degree of stem cell gene expression correlates with patient prognosis. Lgr5(+) or CD133(+) epithelial stem cells (EpiSCs) have recently been identified and these cells are susceptible to neoplastic transformation. It is unclear, however, whether genes enriched in EpiSCs also contribute in tumor malignancy. Endometrial endometrioid carcinoma (EEC) is a dominant type of the endometrial cancers and is still among the most common female cancers. Clinically endometrial carcinoma is classified into 4 FIGO stages by the degree of tumor invasion and metastasis, and the survival rate is low in patients with higher stages of tumors. Identifying genes shared between advanced tumors and stem cells will not only unmask the mechanisms of tumor malignancy but also provide novel therapeutic targets.

Results

To identify EpiSC genes in late (stages III-IV) EECs, a molecular signature distinguishing early (stages I-II) and late EECs was first identified to delineate late EECs at the genomics level. ERBB2 and CCR1 were genes activated in late EECs, while APBA2 (MINT2) and CDK inhibitor p16 tumor suppressors in early EECs. MAPK pathway was significantly up in late EECs, indicating drugs targeting this canonical pathway might be useful for treating advanced EECs. A six-gene mini-signature was further identified to differentiate early from advanced EECs in both the training and testing datasets. Advanced, invasive EECs possessed a clear EpiSC gene expression pattern, explaining partly why these tumors are more malignant.

Conclusions

Our work provides new insights into the pathogenesis of EECs and reveals a previously unknown link between adult stem cells and the histopathological traits of EECs. Shared EpiSC genes in late EECs may contribute to the stem cell-like phenotypes shown by advanced tumors and hold the potential of being candidate therapeutic targets and novel prognosis biomarkers.
The hemolytic and cytolytic activities of Serratia marcescensphospholipase A (PhlA) depend on lysophospholipid production by PhlA
Authors: Shimuta Ken , Ohnishi Makoto , Iyoda Sunao , Gotoh Naomasa , Koizumi Nobuo , Watanabe Haruo
Published: December 2009

Background

Serratia marcescensis a gram-negative bacterium and often causes nosocomial infections. There have been few studies of the virulence factors of this bacterium. The onlyS. marcescenshemolytic and cytotoxic factor reported, thus far, is the hemolysin ShlA.

Results

AnS. marcescens shlAB deletion mutant was constructed and shown to have no contact hemolytic activity. However, the deletion mutant retained hemolytic activity on human blood agar plates, indicating the presence of anotherS. marcescenshemolytic factor. Functional cloning ofS. marcescensidentified a phospholipase A (PhlA) with hemolytic activity on human blood agar plates. AphlAB deletion mutant lost hemolytic activity on human blood agar plates. Purified recombinant PhlA hydrolyzed several types of phospholipids and exhibited phospholipase A1 (PLA1), but not phospholipase A2 (PLA2), activity. The cytotoxic and hemolytic activities of PhlA both required phospholipids as substrates.

Conclusion

We have shown that theS. marcescens phlAgene produces hemolysis on human blood agar plates. PhlA induces destabilization of target cell membranes in the presence of phospholipids. Our results indicated that the lysophospholipids produced by PhlA affected cell membranes resulting in hemolysis and cell death.
Association of a de novo16q copy number variant with a phenotype that overlaps with Lenz microphthalmia and Townes-Brocks syndromes
Authors: Bardakjian Tanya M , Schneider Adele S , Ng David , Johnston Jennifer J , Biesecker Leslie G
Published: December 2009

Background

Anophthalmia and microphthalmia are etiologically and clinically heterogeneous. Lenz microphthalmia is a syndromic form that is typically inherited in an X-linked pattern, though the causative gene mutation is unknown. Townes-Brocks syndrome manifests thumb anomalies, imperforate anus, and ear anomalies. We present a 13-year-old boy with a syndromic microphthalmia phenotype and a clinical diagnosis of Lenz microphthalmia syndrome.

Case Presentation

The patient was subjected to clinical and molecular evaluation, including array CGH analysis. The clinical features included left clinical anophthalmia, right microphthalmia, anteriorly placed anus with fistula, chordee, ventriculoseptal defect, patent ductus arteriosus, posteriorly rotated ears, hypotonia, growth retardation with delayed bone age, and mental retardation. The patient was found to have an approximately 5.6 Mb deletion of 16q11.2q12.1 by microarray based-comparative genomic hybridization, which includes theSALL1gene, which causes Townes-Brocks syndrome.

Conclusions

Deletions of 16q11.2q12.2 have been reported in several individuals, although those prior reports did not note microphthalmia or anophthalmia. This region includesSALL1, which causes Townes-Brocks syndrome. In retrospect, this child has a number of features that can be explained by theSALL1deletion, although it is not clear if the microphthalmia is a rare feature of Townes-Brocks syndrome or caused by other mechanisms. These data suggest that rare copy number changes may be a cause of syndromic microphthalmia allowing a personalized genomic medicine approach to the care of patients with these aberrations.
Plasma ATP concentration and venous oxygen content in the forearm during dynamic handgrip exercise
Authors: Wood Rachel E , Wishart Connie , Walker Philip J , Askew Christopher D , Stewart Ian B
Published: December 2009

Background

It has been proposed that adenosine triphosphate (ATP) released from red blood cells (RBCs) may contribute to the tight coupling between blood flow and oxygen demand in contracting skeletal muscle. To determine whether ATP may contribute to the vasodilatory response to exercise in the forearm, we measured arterialised and venous plasma ATP concentration and venous oxygen content in 10 healthy young males at rest, and at 30 and 180 seconds during dynamic handgrip exercise at 45% of maximum voluntary contraction (MVC).

Results

Venous plasma ATP concentration was elevated above rest after 30 seconds of exercise (P < 0.05), and remained at this higher level 180 seconds into exercise (P < 0.05 versus rest). The increase in ATP was mirrored by a decrease in venous oxygen content. While there was no significant relationship between ATP concentration and venous oxygen content at 30 seconds of exercise, they were moderately and inversely correlated at 180 seconds of exercise (r = -0.651, P = 0.021). Arterial ATP concentration remained unchanged throughout exercise, resulting in an increase in the venous-arterial ATP difference.

Conclusions

Collectively these results indicate that ATP in the plasma originated from the muscle microcirculation, and are consistent with the notion that deoxygenation of the blood perfusing the muscle acts as a stimulus for ATP release. That ATP concentration was elevated just 30 seconds after the onset of exercise also suggests that ATP may be a contributing factor to the blood flow response in the transition from rest to steady state exercise.
Microbiological evaluation of the efficacy of two new biodetergents on multidrug-resistant nosocomial pathogens
Authors: Liguori Giorgio , Bagattini Maria , Gallè Francesca , Quartucci Valeria , Di Onofrio Valeria , Negrone Mario , Triassi Maria
Published: December 2009

Background

In the last few years, several outbreaks of nosocomial infections caused by multidrug-resistant pathogenic agents have been observed, and various biocides products were developed in order to control this phenomenon. We investigated the efficacy of two natural biodetergents composed of plants and kelps extracts, BATT1 and BATT2, against multidrug-resistant strains.

Methods

In-vitro antibacterial efficacy of BATT1 and BATT2 against nosocomial multidrug-resistant isolates was assessed using a suspension-inhibition test, with and without bovine serum albumin (BSA). The test was also carried out on glass surfaces with and without BSA.

Results

In vitro tests with both biocidal disinfectants at 25% concentration demonstrated an overall drop in bacterial, mould and yeast counts after 10 min of contact with or without organic substances. For Pseudomonas aeruginosa, it was necessary to use undiluted disinfectants with and without an organic substance. The same results were obtained in tests carried out on glass surfaces for all strains.

Conclusions

The natural products BATT1 and BATT2 behave like good biocides even in presence of organic substances. The use of both disinfectants may be beneficial for reducing hospital-acquired pathogens that are not susceptible to disinfectants.

However, it has to be stressed that all these experiments were carried out in vitro and they still require validation from use in clinical practice.
Circulating endothelial progenitor cells: a new approach to anti-aging medicine?
Authors: Mikirova Nina A , Jackson James A , Hunninghake Ron , Kenyon Julian , Chan Kyle WH , Swindlehurst Cathy A , Minev Boris , Patel Amit N , Murphy Michael P , Smith Leonard , Alexandrescu Doru T , Ichim Thomas E , Riordan Neil H
Published: December 2009

Endothelial dysfunction is associated with major causes of morbidity and mortality, as well as numerous age-related conditions. The possibility of preserving or even rejuvenating endothelial function offers a potent means of preventing/treating some of the most fearful aspects of aging such as loss of mental, cardiovascular, and sexual function.

Endothelial precursor cells (EPC) provide a continual source of replenishment for damaged or senescent blood vessels. In this review we discuss the biological relevance of circulating EPC in a variety of pathologies in order to build the case that these cells act as an endogenous mechanism of regeneration. Factors controlling EPC mobilization, migration, and function, as well as therapeutic interventions based on mobilization of EPC will be reviewed. We conclude by discussing several clinically-relevant approaches to EPC mobilization and provide preliminary data on a food supplement, Stem-Kine, which enhanced EPC mobilization in human subjects.
Base composition, selection, and phylogenetic significance of indels in the recombination activating gene-1 in vertebrates
Authors: Chiari Ylenia , van der Meijden Arie , Madsen Ole , Vences Miguel , Meyer Axel
Published: December 2009

Background

The Recombination Activating Proteins, RAG1 and RAG2, play a crucial role in the immune response in vertebrates. Among the nuclear markers currently used for phylogenetic purposes, Rag1 has especially enjoyed enormous popularity, since it successfully contributed to elucidating the relationships among and within a large variety of vertebrate lineages. We here report on a comparative investigation of the genetic variation, base composition, presence of indels, and selection in Rag1 in different vertebrate lineages (Actinopterygii, Amphibia, Aves, Chondrichthyes, Crocodylia, Lepidosauria, Mammalia, and Testudines) through the analysis of 582 sequences obtained from Genbank. We also analyze possible differences between distinct parts of the gene with different type of protein functions.

Results

In the vertebrate lineages studied, Rag1 is over 3 kb long. We observed a high level of heterogeneity in base composition at the 3rd codon position in some of the studied vertebrate lineages and in some specific taxa. This result is also paralleled by taxonomic differences in the GC content at the same codon position. Moreover, positive selection occurs at some sites in Aves, Lepidosauria and Testudines. Indels, which are often used as phylogenetic characters, are more informative across vertebrates in the 5' than in the 3'-end of the gene. When the entire gene is considered, the use of indels as phylogenetic character only recovers one major vertebrate clade, the Actinopterygii. However, in numerous cases insertions or deletions are specific to a monophyletic group.

Conclusions

Rag1 is a phylogenetic marker of undoubted quality. Our study points to the need of carrying out a preliminary investigation on the base composition and the possible existence of sites under selection of this gene within the groups studied to avoid misleading resolution. The gene shows highly heterogeneous base composition, which affects some taxa in particular and contains sites under positive selection in some vertebrate lineages in the 5'-end. The first part of the gene (5'-end) is more variable than the second (3'-end), and less affected by a heterogeneous base composition. However, in some vertebrate lineages the 5'-end of the gene is not yet widely used for phylogenetic studies.
Lipoid pneumonia presenting as non resolving community acquired pneumonia: a case report
Authors: Hadda Vijay , Khilnani Gopi C , Bhalla Ashu S , Mathur Sandeep
Published: December 2009

Introduction

Lipoid pneumonia is a rare form of pneumonia caused by inhalation or aspiration of fat containing substances like, petroleum jelly, mineral oils, few laxatives etc. It usually presents as insidious onset chronic respiratory illness simulating interstitial lung diseases. Rarely, it may present as an acute respiratory illness, specially, when exposure to fatty substance is acute and/or massive. Radiologically, it may mimic carcinoma, acute or chronic pneumonia, ARDS, or a localized granuloma. Diagnosis of LP requires demonstration of lipid laden macrophages in sputum, bronchoalveolar lavage fluid or fine needle aspiration cytology/biopsy from lung lesion. Treatment of this illness is poorly defined and constitutes supportive therapy and corticosteroids.

Case presentation

A 20-year old Indian farmer was referred to us with a diagnosis of non resolving community acquired pneumonia. Respiratory examination revealed signs of consolidation. Chest radiograph revealed findings suggestive of bilateral consolidation. Sputum and blood culture were sterile. He was treated with prolonged course of various antibiotics without any significant response. For evaluation of non resolving pneumonia fibreoptic bronchoscopy was done. Bronchoalveolar lavage fluid and biopsy from lung lesion showed lipid laden macrophages. Hence diagnosis of lipoid pneumonia was made. Patient was treated with course of corticosteroids with good response. Literature on this rare entity is discussed.

Conclusion

Lipoid pneumonia is a rare form of pneumonia which rarely present acutely resembling community acquired pneumonia and requires high degree of suspicion for diagnosis. Its treatment is difficult and poorly defined. However, prolonged corticosteroids may be effective.
Immunoglobulin G galactosylation and sialylation are associated with pregnancy-induced improvement of rheumatoid arthritis and the postpartum flare: results from a large prospective cohort study
Authors: van de Geijn Fleur E , Wuhrer Manfred , Selman Maurice HJ , Willemsen Sten P , de Man Yaël A , Deelder André M , Hazes Johanna MW , Dolhain Radboud JEM
Published: December 2009

Introduction

Improvement of rheumatoid arthritis (RA) during pregnancy has been causatively associated with increased galactosylation of immunoglobulin G (IgG) N-glycans. Since previous studies were small, did not include the postpartum flare and did not study sialylation, these issues were addressed in the present study.

Methods

Serum from 148 RA cases and 32 healthy controls was collected at several time points before, during and after pregnancy. Improvement during pregnancy and postpartum flare were determined according to the European League Against Rheumatism (EULAR) response criteria. Galactosylation and sialylation of Immunoglobulin G (IgG) and the presence of bisecting N-acetylglucosamine (GlcNAc) were analyzed by matrix-assisted laser desorption/ionization - time of flight - mass spectrometry (MALDI-TOF-MS).

Results

IgG1 and IgG2 galactosylation of the cases and controls increased during pregnancy with a maximum in the third trimester. Galactosylation decreased directly postpartum. IgG galactosylation of controls was at a higher level than cases (P < 0.001 at all time points) and a similar pattern was observed for sialylation. Moreover, there was a good association between galactosylation and sialylation. The increase in galactosylation was significantly more pronounced for cases with improvement than cases without improvement during pregnancy. The reverse was true for deteriorators and non-deteriorators postpartum. The presence of bisecting GlcNAc was not significantly influenced by pregnancy or postpartum for cases and controls.

Conclusions

This large cohort study demonstrates the association of changes in galactosylation with both pregnancy-induced improvement and postpartum flare in RA-patients, suggesting a role for changes in glycosylation in the pregnancy-induced improvement of RA.