bluuebunny/crossref_metadata_2025 huggingface dataset:
The Effect of the Gly139His, Gly143His, and Ser142His Mouse Heme Oxygenase‐1 Mutants on the HO Reaction In Vivo and In Vitro
Authors: Zhou Lingyun , Liu Ying , Zou Chaoxia , Ma Ning , Hui Yang , Lv Guixiang , Zhang Hongyu , Zhou Hong , Gao Xu
Published: November 2010

Heme oxygenase‐1 (HO‐1), which catalyzes the degradation of heme to iron, carbon monoxide, and biliverdin, performs a cytoprotective function. Previous studies on the crystal structure of the human and rat HO‐1 in complex with heme showed that Gly139His (G139H) and Gly143His (G143H) mutants have no HO activity. In the present study, we reported the effect of the G139H, G143H, and Ser142His mutants of mouse HO‐1 on the HO reaction in vivo and in vitro. In vitro, of the mutant transfectants, only Ser142His catalyzed degradation of heme, retaining 31.7% of the wild‐type mouse HO‐1 activity, whereas G139H and G143H mutants exhibited no activity. In vivo, only Tg HO‐1 G143H females presented with anemia, enlarged spleen and tissue iron overload, which was similar to HO‐1−/− mice. The results suggested the critical role of Gly139 and Gly143 in maintaining HO‐1 activity in vitro and the critical role of Gly143 in maintaining HO‐1 activity in vivo. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
The Influence of Passive Stretch and NF‐κB Inhibitors on the Morphology of Dystrophic Muscle Fibers
Authors: Siegel A.S. , Henley S. , Zimmerman A. , Miles M. , Plummer R. , Kurz J. , Balch F. , Rhodes J.A. , Shinn G.L. , Carlson C.G.
Published: November 2010

The triangularis sterni (TS) is an expiratory muscle that is passively stretched during inspiration. The magnitude of passive stretch depends upon the location of individual fibers within the TS muscle, with fibers located more caudally being stretched ∼ 5% to 10% more than fibers in the cephalad region. In the mdx mouse model for muscular dystrophy, the TS exhibits severe pathological alterations that are ameliorated by treatment with inhibitors of the NF‐κB pathway. The purpose of this study was to assess the influence of passive stretch in vivo on fiber morphology in nondystrophic and mdx TS muscles, and the morphological benefits of treating mdx mice with two distinct NF‐κB inhibitors, pyrrolidine dithiocarbamate (PDTC), and ursodeoxycholic acid (UDCA). Transmission electron microscopy revealed Z‐line streaming, hypercontraction, and disassociation of the plasma membrane from the basal lamina in mdx fibers. In both nondystrophic and mdx TS muscles, fiber density was larger in more caudal regions. In comparison with nondystrophic TS, fibers in the mdx TS exhibited substantial reductions in diameter throughout all regions. In vivo treatment with either PDTC or UDCA tended to increase fiber diameter in the middle and decrease fiber diameter in the caudal TS, while reducing centronucleation in the middle region. These results suggest that passive stretch induces hypercontraction and plasma membrane abnormalities in dystrophic muscle, and that differences in the magnitude of passive stretch may influence fiber morphology and the actions of NF‐κB inhibitors on dystrophic morphology. Anat Rec, 2010. © 2010 Wiley‐Liss, Inc.
Volumetric Reconstruction of the Mouse Meibomian Gland Using High‐Resolution Nonlinear Optical Imaging
Authors: Jester Bryan E. , Nien Chyong JY , Winkler Moritz , Brown Donald J. , Jester James V.
Published: November 2010

Recent studies suggest that mouse meibomian glands (MG) undergo age‐related atrophy that mimics changes seen in age‐related human MG dysfunction (MGD). To better understand the structural/functional changes that occur during aging, this study developed an imaging approach to generate quantifiable volumetric reconstructions of the mouse MG and measure total gland, cell, and lipid volume. Mouse eyelids were fixed in 4% paraformaldehyde, embedded in LR White resin and serially sectioned. Sections were then scanned using a 20× objective and a series of tiled images (1.35 × 1.35 × 0.5 mm) with a pixel size of 0.44 μm lateral and 2 μm axial were collected using a Zeiss 510 Meta LSM and a femtosecond laser to simultaneously detect second harmonic generated (SHG) and two‐photon excited fluorescence (TPEF) signals from the tissue sections. The SHG signal from collagen was used to outline and generate an MG mask to create surface renderings of the total gland and extract relevant MG TPEF signals that were later separated into the cellular and lipid compartments. Using this technique, three‐dimensional reconstructions of the mouse MG were obtained and the total, cell, and lipid volume of the MG measured. Volumetric reconstructions of mouse MG showed loss of acini in old mice that were not detected by routine histology. Furthermore, older mouse MG had reduced total gland volume that is primarily associated with loss of the lipid volume. These findings suggest that mice MG undergo “dropout” of acini, similar to that which occurs in human age‐related MGD. Anat Rec, 2011. © 2010 Wiley‐Liss, Inc.
Construction of Heterojunction Nanowires from Polythiophene/Polypyrrole for Applications as Efficient Switches
Authors: Guo Yanbing , Li Yuliang , Li Yongjun , Liu Huibiao , Li Guoxing , Zhao Yingjie , Lin Haowei
Published: November 2010

The design and fabrication of PTh–PPY heterojunction nanowires that exhibits smart responses to electrochemical redox potentials is described. In their oxidized state, PTh–PPY nanowires act as resistors, whilst in their reduced state, they acts as diodes. Furthermore, the electrical transport mode can be reversibly changed by alternately exposing the nanowires to negative and positive potentials. Constructing full‐organic heterojunction nanowires with smart, controllable properties will contribute to the development of intelligent organic devices and organic–electronic circuits on the nanoscale.
Bis‐Coenzyme Q0: Synthesis, Characteristics, and Application
Authors: Wang Xiuwen , Ma Wei , Ying Yilun , Liang Jie , Long Yi‐Tao
Published: November 2010

A methylene‐bridged bis‐coenzyme Q0, bis(2,3‐dimethoxy‐5‐methyl‐l,4‐benzoquinone)methane (Bis‐CoQ0), that shows intramolecular electronic communications has been synthesized for the first time. By employing electrochemical, in situ UV/Vis, and electron paramagnetic resonance (EPR) spectroelectrochemical techniques, the unstable reduced intermediate species—monoradicals, diamagnetic dianions and tetraanions of Bis‐CoQ0—have been observed. The electron‐transfer process can be defined as a three‐step reduction process with a total of four electrons in solution in CH3CN. The chemical reaction in the third redox step process was confirmed by variable temperature cyclic voltammetry. In an aprotic CH3CN solution, the peak potential separation between electron‐transfer steps diminished sequentially with increasing concentration of water. The hydrogen‐bonding interactions between water and the electrochemically reduced intermediates of Bis‐CoQ0 can be estimated by peak potential shifts. The electronic communications of Bis‐CoQ0 may have been blocked when one reduction peak was observed with proper quantities of water in CH3CN solution. The antioxidant defense capacity of Bis‐CoQ0‐protected cells has also been assessed.
Changes in clinicopathological features and survival after gastrectomy for gastric cancer over a 20-year period
Authors: Ahn H S , Lee H-J , Yoo M-W , Jeong S-H , Park D-J , Kim H-H , Kim W H , Lee K U , Yang H-K
Published: November 2010

Background

The pattern of gastric cancer in the Western world is changing, with an increased proportion of tumours in the upper stomach. The aim of this study was to investigate changes in clinicopathological features and survival of patients with resected gastric cancer at a single institution, in an area of high incidence in the Far East.

Methods

Clinical features and pathological findings were compared in patients with gastric cancer who underwent gastrectomy at Seoul National University Hospital during four consecutive periods (1986–1990, 1991–1995, 1996–2000 and 2001–2006).

Results

There were 12 026 patients. The mean age increased from 53·4 years in the first period to 57·4 years in the last (P < 0·001). The proportion of patients aged 70 years or older also increased, reaching 16·1 per cent in the final period. Upper-third cancer increased from 5·3 per cent in the first period to 14·0 per cent in the fourth (P < 0·001). Early gastric cancer (pathological T1) increased continuously over the four time intervals, from 24·8 to 48·9 per cent (P < 0·001). The overall 5-year survival rate increased from 64·0 per cent in the first period to 73·2 per cent at the end (P < 0·001), and this survival improvement was apparent in patients aged 40 years or more.

Conclusion

The mean age of patients with gastric cancer has increased during the past 20 years. The proportion of early gastric cancer and overall survival have gradually increased, especially in patients aged over 40 years.
Detection of cervical metastatic lymph nodes in papillary thyroid carcinoma by Fourier transform infrared spectroscopy
Authors: Liu Y , Xu Y , Liu Y , Zhang Y , Wang D , Xiu D , Xu Z , Zhou X , Wu J , Ling X
Published: November 2010

Background

A previous study demonstrated that Fourier transform infrared (FTIR) spectroscopy can distinguish thyroid cancer from benign thyroid lesions. The aim of this study was to explore the use of FTIR for identifying metastatic lymph nodes of papillary thyroid cancer in vitro, and distinguishing between metastatic and non-metastatic tissue.

Methods

Some 184 freshly removed cervical lymph nodes were obtained from 22 patients with papillary thyroid cancer undergoing thyroid surgery with lymph node dissection. Samples were measured by FTIR spectroscopy before being processed for histopathological diagnosis. The FTIR spectrum of each sample identified 13 bands from 1000 to 4000 cm−1. The peak position, intensity and full width at half maximum of each absorbent band were measured, and the relative intensity ratios were calculated. The FTIR spectra of metastatic lymph nodes were compared with those of non-metastatic nodes, and a linear discriminant analysis was performed based on these data.

Results

Histopathological examination confirmed 61 metastatic and 123 non-metastatic lymph nodes. The FTIR parameters of metastatic and non-metastatic lymph nodes differed owing to the content or configuration alterations of nucleic acids, proteins, lipids and carbohydrates. The sensitivity for FTIR in diagnosing metastatic lymph nodes was 80·3 per cent, the specificity was 91·9 per cent and the accuracy was 88·0 per cent.

Conclusion

FTIR spectroscopy is a novel technique for detection of metastatic lymph nodes and may prove useful in surgery for papillary thyroid cancer.
Comparison of three separate antiadhesive barriers for intraperitoneal onlay mesh hernia repair in an experimental model
Authors: Gruber-Blum S , Petter-Puchner A H , Brand J , Fortelny R H , Walder N , Oehlinger W , Koenig F , Redl H
Published: November 2010

Background

Adhesion formation is a common adverse effect in intraperitoneal onlay mesh (IPOM) surgery. Different methods of adhesion prevention have been developed, including coated meshes and separate antiadhesive barriers (SABs). In this study one type of mesh was tested with different SABs, which were fixed to the sutured mesh using fibrin sealant. The primary aim was to compare adhesion prevention between different SABs. Secondary aims were the assessment of tissue integration and evaluation of SAB fixation with fibrin sealant.

Methods

Thirty-two rats were randomized to one of three treatment groups (SurgiWrap®, Prevadh® and Seprafilm®) or a control group (no SAB). Animals were operated on with an open IPOM technique (8 per group). One macroporous polypropylene mesh per animal (2 × 2 cm) was fixed with four non-absorbable sutures. An antiadhesive barrier of 2·5 × 2·5 cm was fixed with fibrin sealant. After 30 days, adhesion formation, tissue integration, seroma formation, inflammation and vascularization were evaluated macroscopically and by histology.

Results

Prevadh® and Seprafilm® groups showed a significant reduction in adhesion formation compared with the control group. Tissue integration of the mesh was reduced in these groups. Fibrin sealant fixed the SAB to the mesh securely in all groups.

Conclusion

Prevadh® and Seprafilm® are potent materials for the reduction of adhesion formation. A potential relationship between effective adhesion prevention and impaired tissue integration of the implant was observed. Fibrin sealant proved an excellent agent for SAB fixation.
Comparing the Enantioselective Power of Steric and Electrostatic Effects in Transition‐Metal‐Catalyzed Asymmetric Synthesis
Authors: Poater Albert , Ragone Francesco , Mariz Ronaldo , Dorta Reto , Cavallo Luigi
Published: November 2010

The current approach to improve and tune the enantioselective performances of transition‐metal catalysts for asymmetric synthesis is mostly focused to modifications of the steric properties of the ancillary ligands of the active metal. Nevertheless, it is also known that electrostatic effects can have a remarkable role to promote selectivity in asymmetric synthesis. Using the Rh‐catalyzed asymmetric 1,4‐addition of phenylboronic acid to 2‐cyclohexenone leading to chiral 3‐phenylcyclohexanone as an example, we could show that high enantioselectivity can be indeed achieved using catalysts essentially based either on steric or electrostatic effects as the main source of enantioselective induction. In this contribution we suggest that the analysis of the surface of interaction between the catalyst and the substrate could be a useful tool to quantify the power of steric and electrostatic effects of catalysts.
Investigation of Excess‐Electron Transfer in DNA Double‐Duplex Systems Allows Estimation of Absolute Excess‐Electron Transfer and CPD Cleavage Rates
Authors: Fazio Danila , Trindler Christian , Heil Korbinian , Chatgilialoglu Chryssostomos , Carell Thomas
Published: November 2010

To investigate the parameters and rates that determine excess‐electron transfer processes in DNA duplexes, we developed a DNA double‐duplex system containing a reduced and deprotonated flavin donor at the junction of two duplexes with either the same or different electron acceptors in the individual duplex substructures. This model system allows us to bring the two electron acceptors in the duplex substructures into direct competition for injected electrons and this enables us to decipher how the kind of acceptor influences the transfer data. Measurements with the electron acceptors 8‐bromo‐dA (BrdA), 8‐bromo‐dG (BrdG), 5‐bromo‐dU (BrdU), and a cyclobutane pyrimidine dimer, which is a UV‐induced DNA lesion, allowed us to obtain directly the maximum overall reaction rates of these acceptors and especially of the TT dimer with the injected electrons in the duplex. In line with previous observations, we detected that the overall dimer cleavage rate is about one order of magnitude slower than the debromination of BrdU. Furthermore, we present a more detailed explanation of why sequence dependence cannot be observed when a TT dimer is used as the acceptor and we estimate the absolute excess‐electron hopping rates.
A Study on the Pollution and Water Quality Modeling of the River Buyuk Menderes, Turkey
Authors: Koç Cengiz
Published: November 2010

The aim of the study was to determine the effects of existing and planned facilities on the water quality, and to propose some measures for the protection and improvement of water quality in the basin. For this purpose, the water quality was monitored on the river itself during the last 2 years 2008–2009. After the evaluation of the data collected by using computerized methods, water quality map was prepared, and the MODQUAL mathematical model was applied to the basin to determine the probable effects of different scenarios on the water quality of the river. The simulated water quality variables were: NH3–N, NO3–N, NO2–N, BOD5, DO, o‐PO4, and COD. At the end of the study, it was determined that water quality of Büyük Menderes river and its effluent presents generally polluted water quality in terms of various observed parameter groups. Values obtained by modeling in irrigation season are presented comparatively with analytically measured values. Analytical and modeling results of six of those parameters – except NO3–N – presented regular consistency. In winter season, a general consistency was provided in modeling of all parameters. It was purposed that the waste water originated from domestic and industrial activities should be treated before discharging them to the water bodies, and amount of fertilizer and pesticides used in agriculture should be under strict control throughout the basin in order to protect the water quality and prevent pollution of the water resources.
Successful nontransplant resection of POST‐TEXT III and IV hepatoblastoma
Authors: Lautz Timothy B. , Ben‐Ami Tamar , Tantemsapya Niramol , Gosiengfiao Yasmin , Superina Riccardo A.
Published: November 2010

BACKGROUND:

Liver transplantation is increasingly advocated as primary surgical therapy for children with hepatoblastoma involving 3 or 4 sectors of the liver after neoadjuvant chemotherapy. This study evaluated the results of nontransplant hepatectomy in children who might otherwise have been considered for liver transplantation.

METHODS:

All children who underwent resection at a single institution from 1998 to 2009 for POST‐TEXT IV or centrally located POST‐TEXT III hepatoblastoma after neoadjuvant chemotherapy were reviewed.

RESULTS:

Fourteen children (7 boys) with a median age of 8 months at diagnosis met study criteria. Pulmonary metastases in 3 patients were resected in 2 and resolved with chemotherapy in 1 patient. Preoperative grouping after neoadjuvant chemotherapy was POST‐TEXT IV in 3 patients and POST‐TEXT III in 11 patients. Thirteen of 14 (93%) children who underwent aggressive resection despite being potential candidates for primary transplantation were alive and tumor‐free with a median follow‐up of 57 months. Observed survival rates at 1, 2, and 5 years were 93%, 91%, and 88% respectively. Event‐free survival rates at 1, 2, and 5 years were 93%, 91%, and 75%, respectively.

CONCLUSIONS:

Excellent survival (93%) was obtained with aggressive resection in children with POST‐TEXT III and IV hepatoblastoma meeting criteria for transplant referral. The 1 death occurred in a patient with unfavorable small cell histology. These children should be managed at institutions experienced in both advanced pediatric hepatobiliary surgery and transplantation. Operative exploration was frequently required to ultimately determine which tumors can be resected and which require transplantation. Cancer 2011. © 2010 American Cancer Society.
Disease and host characteristics as predictors of time to first bone metastasis and death in men with progressive castration‐resistant nonmetastatic prostate cancer
Authors: Smith Matthew R. , Cook Richard , Lee Ker‐Ai , Nelson Joel B.
Published: November 2010

BACKGROUND:

The natural history of castration‐resistant nonmetastatic prostate cancer is poorly defined.

METHODS:

The authors used data from 331 subjects in the placebo group of a randomized controlled trial to evaluate the relations of disease and host characteristics with time to first bone metastases in men with prostate cancer, rising prostate‐specific antigen (PSA) despite androgen deprivation therapy, and no radiographic evidence of metastases. Relations between baseline covariates and clinical outcomes were assessed by Cox proportional hazard analyses. Covariates in the model were age, body mass index, prior prostatectomy, prior orchiectomy, Gleason score, performance status, PSA, urinary N‐telopeptide, bone alkaline phosphatase, albumin, lactate dehydrogenase, and hemoglobin.

RESULTS:

At 2 years, 46% of subjects had developed bone metastases, and 20% had died. Median bone metastasis‐free survival was 25 months. In multivariate analyses, baseline PSA ≥13.1 ng/mL was associated with shorter overall survival (relative risk [RR], 2.34; 95% confidence interval [CI], 1.71–3.21; P < .0001), time to first bone metastasis (RR, 1.98; 95% CI, 1.43‐2.74; P < .0001), and bone metastasis‐free survival (RR, 1.98; 95% CI, 1.45–2.70; P < .0001). PSA velocity was significantly associated with overall and bone metastasis‐free survival. Other covariates were not consistently associated with clinical outcomes.

CONCLUSIONS:

In men with progressive castration‐resistant prostate cancer and no detectable metastases, baseline PSA was significantly associated with time to first bone metastasis, bone metastasis‐free survival, and overall survival. Other disease and host characteristics, including body mass index and bone turnover markers, were not consistently associated with clinical outcomes. Cancer 2011. © 2010 American Cancer Society.
Determinants of Pulmonary Blood Flow Distribution
Authors: Glenny Robb W. , Robertson H. Thomas
Published: November 2010

The primary function of the pulmonary circulation is to deliver blood to the alveolar capillaries to exchange gases. Distributing blood over a vast surface area facilitates gas exchange, yet the pulmonary vascular tree must be constrained to fit within the thoracic cavity. In addition, pressures must remain low within the circulatory system to protect the thin alveolar capillary membranes that allow efficient gas exchange. The pulmonary circulation is engineered for these unique requirements and in turn these special attributes affect the spatial distribution of blood flow. As the largest organ in the body, the physical characteristics of the lung vary regionally, influencing the spatial distribution on large‐, moderate‐, and small‐scale levels. © 2011 American Physiological Society.Compr Physiol1:39‐59, 2011..
Gaseous Therapeutics in Acute Lung Injury
Authors: Ryter Stefan W. , Choi Augustine M. K.
Published: November 2010

Acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remain major causes of morbidity and mortality in critical care medicine despite advances in therapeutic modalities. ALI can be associated with sepsis, trauma, pharmaceutical or xenobiotic exposures, high oxygen therapy (hyperoxia), and mechanical ventilation. Of the small gas molecules (NO, CO, H2S) that arise in human beings from endogenous enzymatic activities, the physiological significance of NO is well established, whereas that of CO or H2S remains controversial. Recent studies have explored the potential efficacy of inhalation therapies using these small gas molecules in animal models of ALI. NO has vasoregulatory and redox‐active properties and can function as a selective pulmonary vasodilator. Inhaled NO (iNO) has shown promise as a therapy in animal models of ALI including endotoxin challenge, ischemia/reperfusion (I/R) injury, and lung transplantation. CO, another diatomic gas, can exert cellular tissue protection through antiapoptotic, anti‐inflammatory, and antiproliferative effects. CO has shown therapeutic potential in animal models of endotoxin challenge, oxidative lung injury, I/R injury, pulmonary fibrosis, ventilator‐induced lung injury, and lung transplantation. H2S, a third potential therapeutic gas, can induce hypometabolic states in mice and can confer both pro‐ and anti‐inflammatory effects in rodent models of ALI and sepsis. Clinical studies have shown variable results for the efficacy of iNO in lung transplantation and failure for this therapy to improve mortality in ARDS patients. No clinical studies have been conducted with H2S. The clinical efficacy of CO remains unclear and awaits further controlled clinical studies in transplantation and sepsis. © 2011 American Physiological Society.Compr Physiol1:105‐121, 2011.
Pulmonary Vascular Disease Related to Hemodynamic Stress in the Pulmonary Circulation
Authors: Chan Stephen Y , Loscalzo Joseph
Published: November 2010

Hemodynamic stress in the pulmonary vessel is directly linked to the development of vascular remodeling and dysfunction, ultimately leading to pulmonary hypertension. Recently, some advances have been made in our molecular understanding of the exogenous upstream stimuli that initiate hemodynamic pertubations as well as the downstream vasoactive effectors that control these responses. However, much still remains unknown regarding how these complex signaling pathways connect in order to result in these characteristic pathophysiological changes. This chapter will describe our current understanding of and needed areas of research into the clinical, physiological, and molecular changes associated with pressure/volume overload in the pulmonary circulation. © 2011 American Physiological Society.Compr Physiol1:123‐139, 2011.
Hypoxic Pulmonary Hypertension of the Newborn
Authors: Gao Yuansheng , Raj J Usha
Published: November 2010

Hypoxic pulmonary hypertension of the newborn is characterized by elevated pulmonary vascular resistance and pressure due to vascular remodeling and increased vessel tension secondary to chronic hypoxia during the fetal and newborn period. In comparison to the adult, the pulmonary vasculature of the fetus and the newborn undergoes tremendous developmental changes that increase susceptibility to a hypoxic insult. Substantial evidence indicates that chronic hypoxia alters the production and responsiveness of various vasoactive agents such as endothelium‐derived nitric oxide, endothelin‐1, prostanoids, platelet‐activating factor, and reactive oxygen species, resulting in sustained vasoconstriction and vascular remodeling. These changes occur in most cell types within the vascular wall, particularly endothelial and smooth muscle cells. At the cellular level, suppressed nitric oxide‐cGMP signaling and augmented RhoA‐Rho kinase signaling appear to be critical to the development of hypoxic pulmonary hypertension of the newborn. © 2011 American Physiological Society.Compr Physiol1:61‐79, 2011.
The Adventitia: Essential Role in Pulmonary Vascular Remodeling
Authors: Stenmark Kurt R. , Nozik‐Grayck Eva , Gerasimovskaya Evgenia , Anwar Adil , Li Min , Riddle Suzette , Frid Maria
Published: November 2010

A rapidly emerging concept is that the vascular adventitia acts as a biological processing center for the retrieval, integration, storage, and release of key regulators of vessel wall function. It is the most complex compartment of the vessel wall and comprises a variety of cells including fibroblasts, immunomodulatory cells, resident progenitor cells, vasa vasorum endothelial cells, and adrenergic nerves. In response to vascular stress or injury, resident adventitial cells are often the first to be activated and reprogrammed to then influence tone and structure of the vessel wall. Experimental data indicate that the adventitial fibroblast, the most abundant cellular constituent of adventitia, is a critical regulator of vascular wall function. In response to vascular stresses such as overdistension, hypoxia, or infection, the adventitial fibroblast is activated and undergoes phenotypic changes that include proliferation, differentiation, and production of extracellular matrix proteins and adhesion molecules, release of reactive oxygen species, chemokines, cytokines, growth factors, and metalloproteinases that, collectively, affect medial smooth muscle cell tone and growth directly and that stimulate recruitment and retention of circulating inflammatory and progenitor cells to the vessel wall. Resident dendritic cells also participate in “sensing” vascular stress and actively communicate with fibroblasts and progenitor cells to simulate repair processes that involve expansion of the vasa vasorum, which acts as a conduit for further delivery of inflammatory/progenitor cells. This review presents the current evidence demonstrating that the adventitia acts as a key regulator of pulmonary vascular wall function and structure from the “outside in.” © 2011 American Physiological Society.Compr Physiol1:141‐161, 2011.
Asymptotical Theory of Runaway Electron Diffusion Due to Magnetic Turbulence in Tokamak Plasmas
Authors: Abdullaev S. S. , Finken K. H. , Kudyakov T. , Lehnen M.
Published: November 2010

Asymptotic theory of transport of runaway electrons in a toroidal plasma in the presence of small‐scale magnetic turbulence is proposed. It is based on relativistic Hamiltonian guiding center equations for runaway electrons in toroidal plasmas. Using the asymptotical analysis the explicit relation between the spectral (m, n)‐ components of perturbation Hamiltonian and the corresponding spectrum of the magnetic turbulence is found. This relation depends only on a few parameters of runaway orbits and magnetic surfaces. The radial profiles of runaway diffusion coefficients are found employing two methods, the quasilinear approximation and the direct calculations using a fast running mapping. The dependence of the shielding factor of the runaway electron parameters and the turbulence spectra is discussed (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Temperature of Particulates in Low‐Pressure rf‐Plasmas in Ar, Ar/H2 and Ar/N2 Mixtures
Authors: Maurer H. R. , Basner R. , Kersten H.
Published: November 2010

The temperature of micro‐particles, confined in the sheath of a capacitively coupled low‐pressure rf‐discharge in front of an Adaptive Electrode, has been measured for different plasma conditions and in different gas mixtures by using temperature‐dependent optical features of the particles. In the range from 10 to 50 Pa, the temperature increase with rising discharge power is found to be more pronounced at low pressures than at higher pressures. Addition of molecular gases to the argon‐plasma may either result in a temperature decrease (as in the case of nitrogen) or in additional heating of the particles (when hydrogen is added). The measured particle temperature is discussed with respect to appearing plasma‐particle interactions which contribute to the particle's energy balance (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Degradation of urine samples and its influence on the 13C/12C ratios of excreted steroids
Authors: Piper Thomas , Geyer Hans , Schänzer Wilhelm
Published: November 2010

The degradation processes in deficiently stored urine samples are well investigated regarding steroid concentrations and diagnostic ratios, such as the quotient of testosterone divided by epitestosterone. In contrast, nothing is known about the influence on carbon isotope ratios (CIR) by inappropriate storage conditions. In general, it is assumed that degradation, i.e. deconjugation or dehydrogenation, does not change CIR and thus CIR can be used in cases where the steroid profile turns out to be invalid.

Therefore, the CIR of urinary steroids was investigated in different urine samples during the course of degradation over a time period of six months. Several steroids excreted as glucuronides (androsterone (A), etiocholanolone (E), testosterone, pregnanediol (PD) and 5α‐ and 5β‐androstane‐3α,17β‐diol) or sulfo‐conjugated (A, E and androst‐5‐ene‐3β,17β‐diol (5EN17b)) were investigated together with their unconjugated correspondents (A, E, PD and 5EN17b) and the main dehydrogenation products (5α‐ and 5β‐androstane‐3,17‐dion and androst‐4‐ene‐3,17‐dion). For this purpose, the exiting methods for CIR determination were extended and validated. In addition, the urinary concentrations of all investigated steroids were monitored.

Particular attention was paid to dehydroepiandrosterone conjugated and unconjugated together with its degradation product 3α,5‐cyclo‐5α‐androstan‐6β‐ol‐17‐one as here the strongest influence on CIR was expected. Copyright © 2010 John Wiley & Sons, Ltd.
Efficient Asymmetric Synthesis of 4H‐Chromene Derivatives through a Tandem Michael Addition–Cyclization Reaction Catalyzed by a Salen–Cobalt(II) Complex
Authors: Dong Zhenhua , Liu Xiaohua , Feng Juhua , Wang Min , Lin Lili , Feng Xiaoming
Published: November 2010

The asymmetric synthesis of 2‐amino‐5‐oxo‐5,6,7,8‐tetrahydro‐4H‐chromene derivatives was achieved through a tandem Michael addition–cyclization reaction of easily available cyclohexane‐1,3‐dione and ethyl 2‐cyano‐3‐phenylacrylates. Moderate to good yields (up to 81 %) and high enantioselectivities (up to 89 % ee) were obtained with a chiral salen–cobalt(II) complex. This process was air tolerant and easily performed, which provides an efficient method for the synthesis of chiral 4H‐chromene derivatives.
Detection of immunogenic parasite and host‐specific proteins in the sera of active and chronic individuals infected with Toxoplasma gondii
Authors: Yeng Chen , Osman Emelia , Mohamed Zeehaida , Noordin Rahmah
Published: November 2010

Toxoplasma gondii infection in pregnant women may result in abortion and foetal abnormalities, and may be life‐threatening in immunocompromised hosts. To identify the potential infection markers of this disease, 2‐DE and Western blot methods were employed to study the parasite circulating antigens and host‐specific proteins in the sera of T. gondii‐infected individuals. The comparisons were made between serum protein profiles of infected (n=31) and normal (n=10) subjects. Antigenic proteins were identified by immunoblotting using pooled sera and monoclonal anti‐human IgM‐HRP. Selected protein spots were characterised using mass spectrometry. Prominent differences were observed when serum samples of T. gondii‐infected individuals and normal controls were compared. A significant up‐regulation of host‐specific proteins, α2‐HS glycoprotein and α1‐B glycoprotein, was also observed in the silver‐stained gels of both active and chronic infections. However, only α2‐HS glycoprotein and α1‐B glycoprotein in the active infection showed immunoreactivity in Western blots. In addition, three spots of T. gondii proteins were detected, namely (i) hypothetical protein chrXII: 3984434‐3 TGME 49, (ii) dual specificity protein phosphatase, catalytic domain TGME 49 and (iii) NADPH‐cytochrome p450 reductase TGME 49. Thus, 2‐DE approach followed by Western blotting has enabled the identification of five potential infection markers for the diagnosis of toxoplasmosis: three are parasite‐specific proteins and two are host‐specific proteins.
Comprehensive analysis of low‐abundance proteins in human urinary exosomes using peptide ligand library technology, peptide OFFGEL fractionation and nanoHPLC‐chip‐MS/MS
Authors: Zhang Yuan , Li Yanyan , Qiu Feng , Qiu Zongyin
Published: November 2010

Human urinary exosomes are 30–100 nm vesicles that originate as the internal vesicles in multivesicular bodies from every renal epithelial cell type facing the urinary track and may serve as a suitable noninvasive starting material for biomarker discovery relevant to a variety of renal disease. To comprehensively explore the low‐abundance proteome, combinatorial peptide ligand libraries, combined with peptide OFFGEL electrophoresis were employed for the enrichment and separation of relatively low‐abundant proteins in urinary exosomes. After analysis by nanoHPLC‐chip‐MS/MS, 512 proteins were identified, including a large number of proteins with extreme molecular weight or extreme pI value, which could not be well mapped by using traditional 2‐D‐gel‐based separation methods. This in‐depth analysis of low‐abundant proteins in urinary exosomes led to an increased understanding of molecular composition of these little vesicles and may be helpful for the discovery of novel biomarker. Our work also provides an effective strategy of concentration and identification of low‐abundance proteome from complex bio‐samples.
Monitoring the tidal Delaware River for ambient toxicity
Authors: MacGillivray A Ronald , Russell David E , Brown Steven S , Fikslin Thomas J , Greene Richard , Hoke Robert A , Nally Christopher , O'Donnell Linda
Published: November 2010

This study assessed ambient waters in an urbanized area of the Delaware River, to determine whether river water samples exhibited chronic lethal or sublethal toxicity when measured in laboratory experiments. Toxicity was assessed at 16 fixed stations in the main-stem river and 29 stations in tributaries of the tidal Delaware River with salinities from 0 to 15 parts per 1000 (ppt) using Pimephales promelas, Americamysis bahia, Menidia beryllina, and Ceriodaphnia dubia in 7-d tests; Pseudokirchneriella subcapitata in a 96-h test; and Hyalella azteca in a 10-d water-only test. The toxicity tests measured organism survival, growth, and reproduction. Results from testing water samples collected in 4 different y indicated that the samples from sites tested in the main-stem of the Delaware River and from the majority of its tributaries did not produce chronic toxicity. The surveys identified tributaries that warrant further assessment for toxicity. Integr Environ Assess Manag 2011;7:466–477. © 2011 SETAC
The NP9 protein encoded by the human endogenous retrovirus HERV‐K(HML‐2) negatively regulates gene activation of the Epstein‐Barr virus nuclear antigen 2 (EBNA2)
Authors: Gross Henrik , Barth Stephanie , Pfuhl Thorsten , Willnecker Vivienne , Spurk Andreas , Gurtsevitch Vladimir , Sauter Marlies , Hu Bin , Noessner Elfriede , Mueller‐Lantzsch Nikolaus , Kremmer Elisabeth , Grässer Friedrich A.
Published: November 2010

Epstein‐Barr virus (EBV) is a human tumour virus that efficiently growth‐transforms primary human B‐lymphocytes in vitro. The viral nuclear antigen 2 (EBNA2) is essential for immortalisation of B‐cells and stimulates viral and cellular gene expression through interaction with DNA‐bound transcription factors. Like its cellular homologue Notch, it associates with the DNA‐bound repressor RBPJκ (CSL/CBF1) thereby converting RBPJκ into the active state. For instance, both EBNA2 and Notch activate the cellular HES1 promoter. In EBV‐transformed lymphocytes, the RNA of the NP9 protein encoded by human endogenous retrovirus HERV‐K(HML‐2) Type 1 is strongly up‐regulated. The NP9 protein is detectable both in EBV‐positive Raji cells, a Burkitt's lymphoma cell line, and in IB4, an EBV‐transformed human lymphoblastoid cell line. NP9 binds to LNX that forms a complex with the Notch regulator Numb. Therefore, the function of NP9 vis‐à‐vis Notch and EBNA2 was analysed. Here, we show that NP9 binds to EBNA2 and negatively affects the EBNA2‐mediated activation of the viral C‐ and LMP2A promoters. In contrast, NP9 did neither interfere in the activation of the HES1 promoter by Notch nor the induction of the viral LMP1 promoter by EBNA2. In an electrophoretic mobility shift analysis, NP9 reduced the binding of EBNA2 to DNA‐bound RBPJκ by about 50%. The down‐regulation of EBNA2‐activity by NP9 might represent a cellular defence mechanism against viral infection or could, alternatively, represent an adaptation of the virus to prevent excessive viral protein production that might otherwise be harmful for the infected cell.
Exposure to professional pest control treatments and the risk of childhood acute lymphoblastic leukemia
Authors: Bailey Helen D. , Armstrong Bruce K. , de Klerk Nicholas H. , Fritschi Lin , Attia John , Scott Rodney J. , Smibert Elizabeth , Milne Elizabeth ,   for the Aus‐ALL Consortium
Published: November 2010

Previous studies suggest that exposure to pesticides increases the risk of childhood acute lymphoblastic leukemia (ALL). The aim of this analysis was to investigate whether professional pest treatments in or around the home before birth or during childhood increased the risk of childhood ALL. Data from 388 cases and 870 frequency‐matched controls were analyzed using unconditional logistic regression, adjusting for study matching variables and potential confounders, to calculate odds ratios (ORs). A meta‐analysis of our findings with the published findings of previous studies was also conducted. The ORs for any professional pest control treatments were 1.19 (95% CI 0.83, 1.69) in the year before pregnancy, 1.30 (95% CI 0.86, 1.97) during pregnancy and 1.24 (95% CI 0.93, 1.65) for those done after the child's birth. The ORs for exposure after birth were highest when it occurred between the ages of two and three years. ORs were elevated for termite treatments before birth. ORs were higher for pre‐B than T cell ALL and for t(12;21) (ETV6‐Runx‐1) than other cytogenetic sub‐types. The pooled OR from a meta‐analysis of our study with three previous studies of professional pest control treatments during pregnancy was 1.37 (95% CI 1.00, 1.88). Our results, and those of our meta‐analysis, provide some evidence of a modestly increased risk of ALL for professional pest control treatments done during the index pregnancy and possibly in the child's early years. The analysis of pooled data from international collaborations may provide more certainty regarding these potentially important associations.
Risk of prostate cancer is not associated with levels of C‐reactive protein and other commonly used markers of inflammation
Authors: Van Hemelrijck Mieke , Jungner Ingmar , Walldius Göran , Garmo Hans , Binda Elisa , Hayday Adrian , Lambe Mats , Holmberg Lars , Hammar Niklas
Published: November 2010

Most population‐based studies studied the association between inflammation and prostate cancer (PCa) by assessing C‐reactive protein (CRP). As these findings have shown inconsistent results, we aimed to also study different markers that have been commonly taken as indications of inflammation. A cohort based on four groups of men (n = 34,891), according to age at cohort entry (45, 55, 65 and 75 years), with measurements of glucose, triglycerides, total cholesterol, haptoglobin, albumin, hemoglobin and leukocytes were selected from the Apolipoprotein Mortality Risk database. A total of 17,937 men had measurements of non‐high‐sensitive CRP. Multivariate Cox proportional hazard models were used to analyze associations between inflammatory markers and PCa. A total of 49 of 12,063 men developed PCa in the age 45 group, whereas 207 of 9,940, 472 of 8,266 and 276 of 3,618 were diagnosed in the age 55, 65 and 75 groups, respectively. Mean follow‐up time was 7.5 years (SD: 3.9). No markers showed an association with PCa risk, nor was there a trend by quartiles or an indication for different PCa risks by strata of hypercholesterolemia, hyperglycemia and hypertriglyceridemia status. The studied markers were not found to be associated with PCa risk. These null findings might be due to methodological issues; however, it is unlikely that strong and long‐lasting associations between inflammation and PCa risk were missed as this was a large database with long follow‐up. This indicates need for international consensus on appropriate inflammatory markers in the context of cancer that may be practically applied in large studies.
Direct anti‐cancer effect of oncostatin M on chondrosarcoma
Authors: David Emmanuelle , Guihard Pierre , Brounais Bénédicte , Riet Anne , Charrier Céline , Battaglia Séverine , Gouin François , Ponsolle Stéphanie , Bot Ronan Le , Richards Carl D. , Heymann Dominique , Rédini Françoise , Blanchard Frédéric
Published: November 2010

The cytokine Oncostatin M (OSM) is cytostatic, pro‐apoptotic and induces differentiation of osteosarcoma cells into osteocytes, suggesting new adjuvant treatment for these bone‐forming sarcomas. However, OSM systemic over‐expression could lead to adverse side effects such as generalized inflammation, neoangiogenesis and osteolysis. We determine here the effect of OSM on chondrosarcoma, another primary bone sarcoma characterized by the production of cartilage matrix and altered bone remodelling. Chondrosarcomas are resistant to conventional chemotherapy and radiotherapy, and wide surgical excision remains the only available treatment. We found that OSM blocked the cell cycle in four of five chondrosarcoma cell lines, independently of p53 and presumably through the JAK3/STAT1 pathway. In two tested cell lines, OSM induced a hypertrophic chondrocyte differentiation, with an induced Cbfa1/SOX9 ratio and induced Coll10, matrix metalloproteinase 13 (MMP13) and RANKL expression. Adenoviral gene transfer of OSM (AdOSM) in the Swarm rat chondrosarcoma (SRC) model indicated that local intra‐tumoral OSM over‐expression reduces chondrosarcoma development not only with reduced tumor proliferation and enhanced apoptosis but also with enhanced RANKL expression, osteoclast formation and reduced bone volumes. Flu‐like symptoms were induced by the AdOSM, but there was no effect on tumor angiogenesis. Therefore, OSM could be considered as a new adjuvant anti‐cancer agent for chondrosarcomas. A local application of this cytokine is presumably needed to overcome the poor vascularization of these tumors and to limit the deleterious effect on other tissues. Its side effect on bone remodeling could be managed with anti‐resorption agents, thus offering potential new lines of therapeutic interventions.
Seromic profiling of colorectal cancer patients with novel glycopeptide microarray
Authors: Pedersen Johannes W. , Blixt Ola , Bennett Eric P. , Tarp Mads A. , Dar Imran , Mandel Ulla , Poulsen Steen S. , Pedersen Anders E. , Rasmussen Susanne , Jess Per , Clausen Henrik , Wandall Hans H.
Published: November 2010

Cancer‐associated autoantibodies hold promise as sensitive biomarkers for early detection of cancer. Aberrant post‐translational variants of proteins are likely to induce autoantibodies, and changes in O‐linked glycosylation represent one of the most important cancer‐associated post‐translational modifications (PTMs). Short aberrant O‐glycans on proteins may introduce novel glycopeptide epitopes that can elicit autoantibodies because of lack of tolerance. Technical barriers, however, have hampered detection of such glycopeptide‐specific autoantibodies. Here, we have constructed an expanded glycopeptide array displaying a comprehensive library of glycopeptides and glycoproteins derived from a panel of human mucins (MUC1, MUC2, MUC4, MUC5AC, MUC6 and MUC7) known to have altered glycosylation and expression in cancer. Seromic profiling of patients with colorectal cancer identified cancer‐associated autoantibodies to a set of aberrant glycopeptides derived from MUC1 and MUC4. The cumulative sensitivity of the array analysis was 79% with a specificity of 92%. The most prevalent of the identified autoantibody targets were validated as authentic cancer immunogens by showing expression of the epitopes in cancer using novel monoclonal antibodies. Our study provides evidence for the value of glycopeptides and other PTM‐peptide arrays in diagnostic measures.
Toxic effects of lead and nickel nitrate on rat liver chromatin components
Authors: Rabbani‐Chadegani III Azra , Fani Nesa , Abdossamadi Sayeh , Shahmir Nosrat
Published: November 2010

The biological activity of heavy metals is related to their physicochemical interaction with biological receptors. In the present study, the effect of low concentrations of nickel nitrate and lead nitrate (<0.3 mM) on rat liver soluble chromatin and histone proteins was examined. The results showed that addition of various concentrations of metals to chromatin solution preceded the chromatin into aggregation and precipitation in a dose‐dependant manner; however, the extent of absorbance changes at 260 and 400 nm was different between two metals. Gel electrophoresis of histone proteins and DNA of the supernatants obtained from the metal‐treated chromatin and the controls revealed higher affinity of lead nitrate to chromatin compared to nickel nitrate. Also, the binding affinity of lead nitrate to histone proteins free in solution was higher than nickel. On the basis of the results, it is concluded that lead reacts with chromatin components even at very low concentrations and induce chromatin aggregation through histone–DNA cross‐links. Whereas, nickel nitrate is less effective on chromatin at low concentrations, suggesting higher toxicity of lead nitrate on chromatin compared to nickel. © 2010 Wiley Periodicals, Inc. J Biochem Mol Toxicol 25:127–134, 2011; View this article online at wileyonlinelibrary.com. DOI 10.1002/jbt.20368