bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectrophotometric Determination of Cimetidine through Charge‐transfer Reaction with 1,5‐Dichloroanthraquinone as a π‐Electron Acceptor
Authors: WEI Xiaoling , DU Liangwei , WANG Lisheng , WEI Chunliu , JIANG Zhiliang
Published: August 2009

Cimetidine reacting with 1,5‐dichloroanthraquinone in acetone solution can produce a charge‐transfer complex that shows a strong absorption peak at 343 nm. The absorption value at 343 nm increased with cimetidine concentration in the range of 0.01–0.5 µg/mL, with regression coefficient of 0.9995 and detection limit of 0.006 µg/mL. This simple and sensitive method has been successfully applied to determine cimetidine in tablets and capsules, with average recovery of (98.47±0.92)% and (97.07±1.16)%, respectively. Furthermore, the mole ratio of the complex between cimetidine and 1,5‐dichloroanthraquinone is 2:1, and the mechanism of charge‐transfer reaction is explored.
Synthesis and Antimicrobial Activity of Some 3‐Substituted‐5,6‐dimethoxy‐2,3‐dihydrobenzo[d]thiazol‐2‐one
Authors: El‐HAMOULY Wageeh Salih , AMINE Kamelia Mahmoud , ABBAS Eman Moustafa Hasan , ABDEL‐MAGUID Eman Ali
Published: August 2009

Sixteen new compounds derived from the 2,3‐dihydrobenzo[d]thiazol‐2‐one template with various side‐chains in position‐3 were synthesized and evaluated for their antimicrobial activity. Antibacterial and antifungal screening of the compounds prepared showed that 5,6‐dimethoxy‐3‐(2‐oxo‐propyl)‐2,3‐dihydrobenzo[d]thiazol‐2‐one (3g) exhibited the highest activity.
Venous thromboembolism and nonsmall cell lung cancer
Authors: Hicks Lisa K. , Cheung Matthew C. , Ding Keyue , Hasan Baktiar , Seymour Lesley , Le Maître Aurélie , Leighl Natasha B. , Shepherd Frances A.
Published: August 2009

BACKGROUND:

Advanced nonsmall cell lung cancer (NSCLC) is associated with venous thromboembolism (VTE). However, to the authors' knowledge, the incidence of VTE in early NSCLC, predictors of VTE, and the prognostic significance of VTE in NSCLC have not been explored.

METHODS:

Individual patient data from 3 National Cancer Institute of Canada Clinical Trials Group trials were analyzed (n = 1987 patients). Clinical Trial BR.10 was a randomized study of postoperative vinorelbine and cisplatin versus observation in patients with stage IB/II NSCLC (grading determined according to the TNM staging system). Clinical Trial BR.18 was a randomized study of paclitaxel and carboplatin with or without the metalloproteinase inhibitor BMS‐275291 in patients with advanced NSCLC. BR.21 was a randomized study of erlotinib versus placebo in patients with previously treated NSCLC. The relations between VTE, treatment, concomitant medications, and patient characteristics were explored in univariate and multivariate analyses. Survival analysis was completed using Cox regression.

RESULTS:

The incidence of VTE ranged from 0% in patients with early stage NSCLC on the observation arm of BR.10 to 7.9% in patients with advanced NSCLC who received chemotherapy (BR.18). Patients with early stage NSCLC who received chemotherapy (BR.10) and patients with previously treated NSCLC who received erlotinib or placebo (BR.21) had a VTE incidence of ∼3%. Factors that were found to be predictive of VTE included previous VTE (BR.18; P = .001) and obesity (BR.10; P = .03). In patients with advanced NSCLC, VTE was associated with shorter survival (BR.18: hazard ratio [HR], 1.61; 95% confidence interval [95% CI], 1.26‐2.07 [P = .0002]; BR.21: HR, 2.18; 95% CI, 1.57‐3.04 [P < .0001]).

CONCLUSIONS:

In patients with both early stage and advanced stage NSCLC, VTE occurred more frequently in patients who received chemotherapy (but not erlotinib or BMS‐275291). In patients with advanced stage NSCLC, VTE was associated with obesity and a history of VTE. VTE was found to be prognostic in patients with advanced stage NSCLC. Cancer 2009. © 2009 American Cancer Society.
Standardizing care in medical oncology
Authors: Hains Isla M. , Fuller Joanne M. , Ward Robyn L. , Pearson Sallie‐Anne
Published: August 2009

BACKGROUND:

Medical oncology is embracing information technology to standardize care and improve patient outcomes, with a range of Web‐based systems used internationally. The authors' aim was to determine the factors affecting the uptake and use of a Web‐based protocol system for medical oncology in the Australian setting.

METHODS:

The authors conducted 50 interviews and observed medical oncology physicians, nurses, and pharmacists in their treatment setting at 6 hospitals in different geographic locations.

RESULTS:

The Web‐based system plays a major role in guiding oncology treatment across participating sites. However, its use varies according to hospital location, clinician roles, and experience. A range of issues impact on clinicians' attitudes toward and use of the Web‐based system. Important factors are clinician‒specific (eg, their need for autonomy and perceptions of lack of time) or environmental (eg, hospital policy on protocol use, endorsement of the system, and the availability of appropriate infrastructure, such as sufficient computers). The level of education received regarding the system was also found to be integral to its ongoing use.

CONCLUSIONS:

Although the provision of high‐quality evidence‐based resources, electronic or otherwise, is essential for standardizing care and improving patient outcomes, the authors' findings demonstrate that this alone does not ensure uptake. It is important to understand end‐users, the environment in which they operate, and the basic infrastructure required to implement such a system. Implementation must also be accompanied by continuing education and endorsement to ensure both long‐term sustainability and use of the system to its full potential. Cancer 2009. © 2009 American Cancer Society.
Fluorescence in situ hybridization studies on direct smears
Authors: Monaco Sara E. , Teot Lisa A. , Felgar Raymond E. , Surti Urvashi , Cai Guoping
Published: August 2009

BACKGROUND:

In the fine‐needle aspiration biopsy (FNAB) diagnosis of B‐cell non‐Hodgkin lymphomas (B‐NHL), the role of flow cytometry (FC) can be limited because of nondiagnostic findings. Fluorescence in situ hybridization (FISH) studies, similar to FC, can be helpful in establishing clonality and in subclassifying the lymphoma. The aim of the current study was to determine whether FISH studies performed on unstained direct smears improved the ability to diagnose and/or subclassify B‐NHL on FNAB.

METHODS:

A total of 181 cases of B‐NHL diagnosed by FNAB were retrieved. The cytomorphology, ancillary study results, clinical information, and available pathologic follow‐up were reviewed.

RESULTS:

Of the 181 cases, FISH studies were performed in 106 cases (59%). The indications for FISH studies were for subclassification (59 cases; 56%) and nondiagnostic or unavailable FC results (47 cases; 44%). Of the 59 cases submitted for subclassification, 23 cases (39%) were successfully subclassified. The 47 cases with nondiagnostic or unavailable FC results included cases in which FC demonstrated a surface immunoglobulin‐negative population (19 cases; 40%), had insufficient cellularity (18 cases; 38%), yielded negative results (6 cases; 13%), or had no specimen submitted (4 cases; 9%). In this group, 26 cases (55%) demonstrated an immunoglobulin heavy‐chain gene rearrangement and/or chromosomal translocation.

CONCLUSIONS:

The results of the current study illustrate that FISH studies performed on unstained direct smears play a complementary role to FC in establishing the diagnosis and/or subclassification of B‐NHL. Thus, the preparation of unstained smears at the time of FNAB can be helpful for potential FISH studies. Cancer (Cancer Cytopathol) 2009. © 2009 American Cancer Society.
Frequency of circulating iNKT cells among Iranian healthy adults
Authors: Fereidouni Mohammad , Farid Hosseini Reza , Jabbari Azad Farahzad , Schenkel Jason , Varasteh Abdolreza , Mahmoudi Mahmoud
Published: August 2009

Background:

Invariant natural killer T cells (iNKT) are a small subset of T lymphocytes which are involved in a wide variety of immune responses. Human studies have reported a wide variation in the number of circulating iNKT cell among healthy donors as well as in some immunologic disorders while there is no or little data about the factors which affect the pool of circulating iNKT cells in human.

Given the importance of iNKT cells in immunologic responses and variation in the number and phenotype of iNKT cells, the aim of this study was to evaluate the frequency of circulating iNKT cells in a cohort of healthy Iranian adults.

Methods:

The number of circulating iNKT cells was measured among PBMC in a group of healthy Iranian adults by flow cytometry. iNKT cells were identified by using 6B11 monoclonal antibody or by coexpression of TCR Vα24 and Vβ11 chain.

Results:

The mean frequency of 6B11‐iNKT cells and Vα24‐Vβ11 iNKT cells among T lymphocytes, were 0.54% and 0.31%, respectively. Forty‐five percent of 6B11‐iNKT cells were CD4 positive, and there was a weak but significant inverse correlation between total 6B11‐iNKT cells and their CD4‐positive subset. There was no significant difference in the frequency of iNKT cells between males and females.

Conclusions:

Results of this study show that the frequency of iNKT cells is fairly high among the Iranian population and suggest matching of study population for age, sex, and ethnic background in iNKT‐related research. More studies are necessary to understand the factors that can affect the variation in the number of iNKT cells in healthy humans. © 2009 Clinical Cytometry Society
NK cells from tuberculous pleurisy express high ICAM‐1 levels and exert stimulatory effect on local T cells
Authors: Schierloh Pablo , Yokobori Noemí , Geffner Laura , Balboa Luciana , Romero María M. , Musella Rosa M. , Alemán Mercedes , Castagnino Jorge , Basile Juan , de la Barrera Silvia S. , Abbate Eduardo , Sasiain María C.
Published: August 2009

Tuberculous pleurisy, one of the most common manifestations of extrapulmonary tuberculosis, is characterized by a T‐cell‐mediated hypersensitivity reaction along with a Th1 immune profile. In this study, we investigated functional cross‐talk among T and NK cells in human tuberculous pleurisy. We found that endogenously activated pleural fluid‐derived NK cells express high ICAM‐1 levels and induce T‐cell activation ex vivo through ICAM‐1. Besides, upon in vitro stimulation with monokines and PAMP, resting peripheral blood NK cells increased ICAM‐1 expression leading to cellular activation and Th1 polarization of autologous T cells. Furthermore, these effects were abolished by anti‐ICAM‐1 Ab. Hence, NK cells may contribute to the adaptive immune response by a direct cell‐contact‐dependent mechanism in the context of Mycobacterium tuberculosis infection.
Towards Allosteric Receptors – Synthesis of Resorcinarene‐Functionalized 2,2′‐Bipyridines and Their Metal Complexes
Authors: Staats Holger , Eggers Friederike , Haß Oliver , Fahrenkrug Frank , Matthey Jens , Lüning Ulrich , Lützen Arne
Published: August 2009

Based on a first example of an allosteric hemicarcerand (1) we prepared four new 2,2′‐bipyridines that carry resorcinarene moieties in a highly convergent manner. Upon coordination to suitable transition metal ions or their complexes these compounds undergo conformational changes in a way that they switch between “open” and “closed” forms (2, 3, and 4) or vice versa (5), thus, bringing together or separating the two functional moieties on the central bipyridine. Among the transition metal complexes that act as effectors for the conformational switching, [Re(CO)5Cl] and monomeric copper(I) complexes of sterically hindered 2,9‐arylated 1,10‐phenanthrolines proved to be very effective. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
A Concise Stereoselective Synthesis of 2‐Substituted 1‐Aminocyclopropanecarboxylic Acids
Authors: Pradhan Tarun K. , Joosten Antoine , Vasse Jean‐Luc , Bertus Philippe , Karoyan Philippe , Szymoniak Jan
Published: August 2009

A simple and stereoselective method for the preparation of (Z)‐2‐substituted 1‐aminocyclopropanecarboxylic acids is described. The common key step for these reaction sequences involves the stereoselective Ti‐mediated coupling of benzyloxy nitrile and homoallylic alcohol. The resulting 2‐hydroxyethyl‐substituted cyclopropylamine can be transformed shortly into various cyclopropane amino acid analogues on the gram scale, in good overall yields. Several syntheses of 2,3‐methanoamino acids, that is, ACCs derived from proteinogenic α‐amino acids or analogues, such as glutamic acid, arginine, homoarginine, and lysine derivatives are presented to exemplify the usefulness of the method. Additionally, starting from cyanoesters, spirocyclopropane γ‐amino acid analogues are available in this way. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Mechanofluorochromism of a Series of Benzofuro[2,3‐c]oxazolo[4,5‐a]carbazole‐Type Fluorescent Dyes
Authors: Ooyama Yousuke , Kagawa Yusuke , Fukuoka Hiroshi , Ito Genta , Harima Yutaka
Published: August 2009

Mechanofluorochromism is found for a series of benzofuro[2,3‐c]oxazolo[4,5‐a]carbazole‐type fluorophores (1a–1d) having cyano groups as acceptor: grinding of 1a–1d induces a fluorescent color change with an enhanced quantum yield, and the fluorescent color is recovered by heating or exposure to solvent vapor. Interestingly, both absorption and emission peaks are redshifted by grinding, in conflict with the common view. On the basis of time‐resolved fluorescence spectroscopy, X‐ray powder diffraction (XRD), differential scanning calorimetry (DSC), and single‐crystal X‐ray structural analysis, the mechanofluorochromism observed with this new class of fluorescent dyes is found to accompany a reversible switching between crystalline and amorphous states with changes of molecular arrangement and intermolecular π–π interactions. An essential role of a strong donor‐π‐acceptor character of the dyes is pointed out for the manifestation of the observed mechanofluorochromism.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2009)
Spatio‐temporal point process filtering methods with an application
Authors: Frcalová Blažena , Beneš Viktor , Klement Daniel
Published: August 2009

The paper deals with point processes in space and time and the problem of filtering. Real data monitoring the spiking activity of a place cell of hippocampus of a rat moving in an environment are evaluated. Two approaches to the modelling and methodology are discussed. The first one (known from literature) is based on recursive equations which enable to describe an adaptive system. Sequential Monte Carlo methods including particle filter algorithm are available for the solution. The second approach makes use of a continuous time shot‐noise Cox point process model. The inference of the driving intensity leads to a nonlinear filtering problem. Parametric models support the solution by means of the Bayesian Markov chain Monte Carlo methods, moreover the Cox model enables to detect adaptivness. Model selection is discussed, numerical results are presented and interpreted. Copyright © 2009 John Wiley & Sons, Ltd.
Differentiation and neural integration of hippocampal neuronal progenitors: Signaling pathways sequentially involved
Authors: Akchiche Nassila , Bossenmeyer‐Pourié Carine , Pourié Grégory , Koziel Violette , Nédélec Emmanuelle , Guéant Jean‐Louis , Daval Jean‐Luc
Published: August 2009

In the context of their potential implication in regenerative strategies, we characterized cell mechanisms underlying the fate of embryonic rat hippocampal H19–7 progenitors in culture upon induction of their differentiation, and tested their capacities to integrate into a neuronal network in vitro. Without addition of growth factors, nearly 100% of cells expressed various neuronal markers, with a progressive rise of the expression of Synapsin I and II, suggesting that cells developed as mature neurons with synaptogenic capacities. Fully differentiated neurons were identified as glutamatergic and expressed the receptor‐associated protein PSD‐95. Quantification of ATP showed that 60% of cells died within 24 h after differentiation. Cell death was shown to imply Erk1/2‐dependent intrinsic mitochondrial apoptosis signaling pathway, with activation of caspase‐9 and ‐3, finally leading to single‐strand DNA. Surviving neurons displayed high levels of Akt, phospho‐Akt, and antiapoptotic proteins such as Bcl‐2 and Bcl‐XL, with decreased caspase activation. In the absence of trophic support, the proapoptotic death‐associated protein (DAP) kinase was dramatically stimulated by 24 h postdifferentiation, along with increased levels of p38 and phospho‐p38, and caspase reactivation. These findings show that different signaling pathways are sequentially triggered by differentiation, and highlight that ultimate cell death would involve p38 and DAP kinase activation. This was supported by the improvement of cell survival at 24‐h postdifferentiation when cells were treated by PD169316, a specific inhibitor of p38. Finally, when seeded on rat hippocampal primary cultured neurons, a significant number of differentiated H19–7 cells were able to survive and to develop cell–cell communication. © 2009 Wiley‐Liss, Inc.
BEX2 regulates mitochondrial apoptosis and G1 cell cycle in breast cancer
Authors: Naderi Ali , Liu Ji , Bennett Ian C.
Published: August 2009

We have recently demonstrated that BEX2 is differentially expressed in primary breast tumors and BEX2 expression is required for the Nerve Growth factor inhibition of ceramide‐induced apoptosis in breast cancer. In this study we investigate the functional role of BEX2 in the survival and growth of breast cancer cells. We demonstrate that BEX2 downregulation induces mitochondrial apoptosis and sensitizes breast cancer cells to the pro‐apoptotic effects of ceramide, doxorubicin and staurosporine. In addition, BEX2 overexpression protects the breast cancer cells against mitochondrial apoptosis. We show that this effect of BEX2 is mediated through the modulation of Bcl‐2 protein family, which involves the positive regulation of anti‐apoptotic member Bcl‐2 and the negative regulation of pro‐apoptotic members BAD, BAK1 and PUMA. Moreover, our data suggests that BEX2 expression is required for the normal cell cycle progression during G1 in breast cancer cells through the regulation of cyclin D1 and p21. To further support the significance of BEX2 in the pathogenesis of breast cancer we demonstrate that BEX2 overexpression is associated with a higher activation of the Bcl‐2/NF‐κB pathway in primary breast tumors. Furthermore, we show that BEX2 downregulation results in a higher expression and activity of protein phosphatase 2A. The modulation of protein phosphatase 2A, which is also known to mediate the cellular response to ceramide, provides a possible mechanism to explain the BEX2‐mediated cellular effects. This study demonstrates that BEX2 has a significant role in the regulation of mitochondrial apoptosis and G1 cell cycle in breast cancer.
MLL/AF10(OM‐LZ)‐immortalized cells expressed cytokines and induced host cell proliferation in a mouse bone marrow transplantation model
Authors: Fu Jen‐Fen , Hsu Cheng‐Lung , Shih Lee‐Yung
Published: August 2009

Several mouse models studying the MLL fusion‐induced leukemic transformation showed that a myeloproliferation stage precedes leukemia or occurred as the only phenotype of hematological disorder in mice. We established 6 MLL/AF10(OM‐LZ)‐immortalized cell lines by retrovirally transducing the fusion gene into bone marrow cells from B6 or congenic GFP‐B6 mice. Immunophenotypic and cytological analyses revealed that the immortalized cell lines could be divided into 2 types. Type I had a high percentage of cells expressing monocytic lineage marker CD115 in the medium containing IL3 and could terminally differentiate into granulocytes and monocytes in response to granulocyte colony‐stimulating factor (G‐CSF) and macrophage colony‐stimulating factor (M‐CSF) treatments, respectively. On the other hand, type II had a low percentage of cells expressing CD115. The type II cell lines could not differentiate into granulocytes by G‐CSF treatment and died rapidly in response to M‐CSF treatment. Transplantation of both types I and II cells induced lethal myeloproliferative disease (MPD)‐like myeloid leukemia in most of the sublethally irradiated B6 mice. Flow cytometric analysis of GFP and lineage markers of the peripheral blood cells from MPD mice revealed that the monocytes and granulocytes were generated not only from the donor cells but also from the host cells. RT‐PCR analysis revealed that the MLL/AF10(OM‐LZ)‐immortalized cells expressed mRNAs encoding colony‐stimulating factors (CSFs) of M‐CSF and GM‐CSF and inflammatory cytokines of IL‐1α, IL‐1β and TNF‐α. Our results showed that the MLL/AF10(OM‐LZ)‐immortalized cells could induce host cell proliferation in the transplanted mice, probably through stimulation by CSFs or cytokines produced by the donor cells.
Occurrence of anticancer activity of prednisolone via adrenalectomy and inhibition of adrenaline in rats
Authors: Suleyman Halis , Cadirci Elif , Albayrak Abdulmecit , Halici Zekai , Gundogdu Cemal , Hacimuftuoglu Ahmet
Published: August 2009

In this study, the anticancer effect of prednisolone was investigated using rats with normal endogen adrenaline levels (intact), reduced adrenaline levels (metyrosine‐induced) and adrenaline deficiency (adrenalectomized) via gastric adenocarcinoma model. Gastric adenocarcinoma was induced with N‐methyl‐N′‐nitro‐N‐nitrosoguanidine (MNNG). According to our experimental results, prednisolone could not prevent MNNG‐induced adenocarcinoma when used alone in intact rats. There were neither macroscopic nor microscopic signs of cancer in the rat groups that received metyrosine and prednisolone. However, dysplasia occurred in the stomachs of 2 of 10 rats that received metyrosine and prednisolone. There was no adenocarcinoma genesis in the stomachs of adrenalectomized rats that received prednisolone alone. However, yohimbine (a selective blocker of α2‐adrenoreceptors) pretreatment in adrenalectomized rats negated the anticancer effect of prednisolone. In conclusion, prednisolone was shown not to be an anticancer agent in intact rats when used alone; however, it has anticancer effects in rats whose adrenaline levels were reduced via adrenalectomy or metyrosine, which is a catecholamine synthesis inhibitor.
Compensating for nonstationary blurring by further blurring and deconvolution
Authors: Zeng Gengsheng L.
Published: August 2009

In many imaging systems, the point spread function (PSF) is nonstationary. Usually, a computation‐intensive iterative algorithm is used to deblur the nonstationary PSF. This article presents a new idea of using a noniterative method to compensate for the spatially variant PSF. This method first further blurs the image with a nonstationary kernel so that the resultant image has a stationary PSF, then deblurs the resultant image using an efficient decovolution technique. The proposed method is illustrated and implemented by single photon emission computed tomography applications. © 2009 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 19, 221–226, 2009
Attenuation map estimation with SPECT emission data only
Authors: Yan Yan , Zeng Gengsheng Lawrence
Published: August 2009

Quantitative single‐photon emission computed tomography can be well achieved if photon attenuation is taken into account in the reconstruction process. Using a transmission scan is a common approach. A dramatic simplification could be made if the attenuation map could be obtained from the emission data. In this article, we propose a new method to estimate the attenuation map using the data consistency conditions of the attenuated Radon transform. It is based on deriving boundaries of the constant regions of the true attenuation map using an iterative algorithm. This new method is tested by Monte Carlo simulations with the attenuation and scattering effects. © 2009 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 19, 271–276, 2009
Contemporary technologies for 3D digitization of Maori and Pacific Island artifacts
Authors: Surendran Nanda K. , Xu Xun W. , Stead Oliver , Silyn‐Roberts Heather
Published: August 2009

Three‐dimensional (3D) digitization is a key aspect in the preservation and exhibition of museum artifacts. The objective of this article is to investigate contemporary technologies for creating accurate 3D digital models of artifacts from the Maori and Pacific heritage and to establish a generic digitization methodology so that the 3D models can be archived and exhibited both over the internet and within museum displays. This process involves procedures for selecting artifacts that are suitable for laser scanning and then setting up the artifact for scanning. This is followed by the actual scanning and postprocessing stages. To achieve this, the Polhemus FastSCAN laser scanner has been used to collect raw point cloud surface data from artifacts of various sizes, shapes, textures, colors, and materials. The article explains the generic steps developed for postprocessing of raw scan data in the form of a cloud of geometric data points to a completely rendered 3D model with colors mapped on to the model. These generic steps involve removal of background noise, enhancement of texture, filling of holes, merging of separate scans, and color mapping. The results from the scanning and postprocessing of a wahaika, (a Maori club‐like weapon) and a Polynesian stone pounder reveal that it is important to use a scanner that is flexible enough to capture all the surface information irrespective of the artifact's geometry, and one with the capability of capturing color information with high accuracy. © 2009 Wiley Periodicals, Inc. Int J Imaging Syst Technol, 19, 244–259, 2009
Phosphorylation of PPP(S/T)P motif of the free LRP6 intracellular domain is not required to activate the Wnt/β‐catenin pathway and attenuate GSK3β activity
Authors: Beagle Brandon , Mi Kaihong , Johnson Gail V.W.
Published: August 2009

The canonical Wnt/β‐catenin signaling pathway plays a critical role in numerous physiological and pathological processes. LRP6 is an essential co‐receptor for Wnt/β‐catenin signaling; as transduction of the Wnt signal is strongly dependent upon GSK3β‐mediated phosphorylation of multiple PPP(S/T)P motifs within the membrane‐anchored LRP6 intracellular domain. Previously, we showed that the free LRP6 intracellular domain (LRP6‐ICD) can activate the Wnt/β‐catenin pathway in a β‐catenin and TCF/LEF‐1 dependent manner, as well as interact with and attenuate GSK3β activity. However, it is unknown if the ability of LRP6‐ICD to attenuate GSK3β activity and modulate activation of the Wnt/β‐catenin pathway requires phosphorylation of the LRP6‐ICD PPP(S/T)P motifs, in a manner similar to the membrane‐anchored LRP6 intracellular domain. Here we provide evidence that the LRP6‐ICD does not have to be phosphorylated at its PPP(S/T)P motif by GSK3β to stabilize endogenous cytosolic β‐catenin resulting in activation of TCF/LEF‐1 and the Wnt/β‐catenin pathway. LRP6‐ICD and a mutant in which all 5 PPP(S/T)P motifs were changed to PPP(A)P motifs equivalently interacted with and attenuated GSK3β activity in vitro, and both constructs inhibited the in situ GSK3β‐mediated phosphorylation of β‐catenin and tau to the same extent. These data indicate that the LRP6‐ICD attenuates GSK3β activity similar to other GSK3β binding proteins, and is not a result of it being a GSK3β substrate. Our findings suggest the functional and regulatory mechanisms governing the free LRP6‐ICD may be distinct from membrane‐anchored LRP6, and that release of the LRP6‐ICD may provide a complimentary signaling cascade capable of modulating Wnt‐dependent gene expression. J. Cell. Biochem. 108: 886–895, 2009. © 2009 Wiley‐Liss, Inc.
PI3K/AKT regulates aggrecan gene expression by modulating Sox9 expression and activity in nucleus pulposus cells of the intervertebral disc
Authors: Cheng Chin‐Chang , Uchiyama Yoshiyasu , Hiyama Akihiko , Gajghate Sachin , Shapiro Irving M. , Risbud Makarand V.
Published: August 2009

The goal of the investigation was to test the hypothesis that the phosphoinositide‐3 kinase (PI3K)/AKT signaling pathway regulates the expression of the major extracellular matrix component of the intervertebral disc, aggrecan, in nucleus pulposus cells. Primary rat nucleus pulposus cells were treated with PI3K inhibitor to measure changes in gene and protein expression. In addition, cells were transfected with various luciferase reporter plasmids to investigate mechanisms of regulation of aggrecan gene expression. We found that treatment of nucleus pulposus cells with a PI3K inhibitor, LY294002 resulted in decreased expression of aggrecan and a reduction in deposition of sulfated glycosaminoglycans. Moreover, pharmacological suppression or co‐expression of dominant negative (DN)‐PI3K or DN‐AKT resulted in downregulation of aggrecan promoter activity. Expression of constitutively active (CA)‐PI3K significantly induced aggrecan promoter activity. We observed that PI3K maintained Sox9 gene expression and activity: inhibition of PI3K/AKT resulted in decreased Sox9 expression, lowered promoter activity, and mediated a reduction in Sox9 transcriptional activity. PI3K effects were independent of phosphorylation status of C‐terminus transactivation domain (TAD) of Sox9. Finally, we noted that in nucleus pulposus cells, PI3K signaling controlled transactivation of p300 (p300‐TAD activity), an important transcriptional co‐activator of Sox9. Results of these studies demonstrate for the first time that PI3K/AKT signaling controls aggrecan gene expression, in part by modulating Sox9 expression and activity in cells of the nucleus pulposus. J. Cell. Physiol. 221: 668–676, 2009. © 2009 Wiley‐Liss, Inc.
Ceramide metabolism determines glioma cell resistance to chemotherapy
Authors: Dumitru Claudia Alexandra , Weller Michael , Gulbins Erich
Published: August 2009

Tumor cell resistance to chemotherapy constitutes a major problem in the treatment of malignant tumors. We here investigated the role of ceramide metabolism for the resistance of glioma cells to treatment with the chemotherapeutic drug, gemcitabine. Gemcitabine triggers a marked release of ceramide in drug‐sensitive cells, while glioma cells that are resistant to gemcitabine, fail to accumulate ceramide. While the release of ceramide is very similar in gemcitabine‐sensitive and resistant glioma cells upon stimulation, resistant glioma cells rapidly consume ceramide upon gemcitabine treatment or exogenous sphingomyelinase stimulation. Pharmacologic or genetic inhibition of glucosyltransferases prevents ceramide consumption in resistant cells and restores sensitivity of resistant glioma cells to gemcitabine. These data suggest that glioma cell resistance to at least some chemotherapeutic drugs is mediated by rapid consumption of ceramide to prevent cell death. J. Cell. Physiol. 221: 688–695, 2009. © 2009 Wiley‐Liss, Inc.
Divergent reactivity in tandem reduction–Michael ring closures of five‐ and six‐membered cyclic enones
Authors: Bunce Richard A. , Nammalwar Baskar , Slaughter LeGrande M.
Published: August 2009

magnified image

In this study, methyl (±)‐1‐(2‐nitrobenzyl)‐4‐oxo‐2‐cyclohexene‐1‐carboxylate and methyl (±)‐(2‐nitrobenzyl)‐4‐oxo‐2‐cyclopentene‐1‐carboxylate were prepared and subjected to reductive cyclization under dissolving metal conditions. The two reactants showed divergent behavior with the six‐ring substrate reacting at the ester carbonyl and the five‐ring substrate closing on the enone double bond. The difference in reactivity is attributed to the conformational flexibility, relative reactivity, and steric environment of C4‐substituted six‐ and five‐membered cyclic enones. J. Heterocyclic Chem., (2009).
Anatomy of virgin and mature externae of Loxothylacus texanus, parasitic on the dark blue crab Callinectes rathbunae (Crustacea: Cirripedia: Rhizocephala: Sacculinidae)
Authors: Alvarez Fernando , Bortolini José Luis , Høeg Jens T.
Published: August 2009

Rhizocephalan parasites are dioecious organisms, in that one or several dwarf males are implanted into the external part of the female parasite soon after it emerges from the interior of the host animal. The structure of the female externa and its resident males is crucial for understanding both the reproductive biology and the taxonomy of these specialized parasites. We use scanning electron microscopy and histological methods to study the anatomy of juvenile and the mature externae of the rhizocephalan barnacle Loxothylacus texanus parasitizing the blue crab Callinectes rathbunae. We put emphasis on the implantation of males and the histology of the female reproductive organs. In the virgin externae, male cyprids attach around a cuticular hood covering the mantle aperture, which is partially blocked by a plug of cuticle so only trichogon larvae, not cyprids, can access the mantle cavity. This resembles the situation known from Sacculina carcini. The mature externa is characterized by a visceral mass that contains the ovary, paired colleteric glands, a single male receptacle, but paired receptacle ducts. The proximal attachment of the visceral mass is located at some distance from the basal stalk, as is characteristic for the genus Loxothylacus. The internal anatomy of the mature externa of L. texanus is in most features similar to that seen in other species of the Sacculinidae, which comprises the majority of rhizocephalan species. However, the single receptacle creates a situation where the two implanted males cannot be kept separate as in most other rhizocephalans, but pass through spermatogenesis in a common chamber. This may have unknown effects on the reproductive biology such as male–male competition. J. Morphol., 2010. © 2009 Wiley‐Liss, Inc.
Fast spin‐echo triple‐echo Dixon: Initial clinical experience with a novel pulse sequence for fat‐suppressed T2‐weighted abdominal MR imaging
Authors: Low Russell N. , Ma Jingfei , Panchal Neeraj
Published: August 2009

Purpose

To evaluate a prototype fast spin echo (FSE) triple‐echo‐Dixon (fTED) technique for breath‐hold, fat‐suppressed, T2‐weighted abdominal imaging.

Materials and Methods

Forty patients underwent breath‐hold T2‐weighted abdominal imaging with fTED and conventional fast recovery (FR) FSE with chemical shift‐selective saturation (CHESS). FRFSE and fTED images were compared for overall image quality, homogeneity of fat suppression, image sharpness, anatomic detail, and phase artifact. Depiction of disease was recorded separately for FRFSE and fTED images.

Results

FTED successfully reconstructed water‐only and fat‐only images from source images in all 40 cases. Water and fat separation was perfect in 36 (0.90) patients. Homogeneity of fat suppression was superior on the fTED images in 38 (0.95) of 40 cases. FTED images showed better anatomic detail in 27 (0.68), and less susceptibility artifact in 20 (0.50). FRFSE images showed less vascular pulsation artifact in 30 (0.75) cases, and less phase artifact in 21 (0.53) cases. There was no difference in depiction of disease for FRFSE and fTED images.

Conclusion

FTED is a robust sequence providing breath‐hold T2‐weighted images with superior fat suppression, excellent image quality, and at least equal depiction of disease compared to conventional breath‐hold T2‐weighted FRFSE imaging. J. Magn. Reson. Imaging 2009;30:569–577. © 2009 Wiley‐Liss, Inc.
Diffusion‐weighted imaging of breast cancer: Correlation of the apparent diffusion coefficient value with prognostic factors
Authors: Kim Sung Hun , Cha Eun Suk , Kim Hyeon Sook , Kang Bong Joo , Choi Jae Jeong , Jung Ji Han , Park Yong Gyu , Suh Young Jin
Published: August 2009

Purpose

To evaluate the role of diffusion‐weighted imaging (DWI) in the detection of breast cancers, and to correlate the apparent diffusion coefficient (ADC) value with prognostic factors.

Materials and Methods

Sixty‐seven women with invasive cancer underwent breast MRI. Histological specimens were analyzed for tumor size and grade, and expression of estrogen receptors (ER), progesterone receptors, c‐erbB‐2, p53, Ki‐67, and epidermal growth factor receptors. The computed mean ADC values of breast cancer and normal breast parenchyma were compared. Relationships between the ADC values and prognostic factors were determined using Wilcoxon signed rank test and Kruskal‐Wallis test.

Results

DWI detected breast cancer as a hyperintense area in 62 patients (92.5 %). A statistically significant difference in the mean ADC values of breast cancer (1.09 ± 0.27 × 10−5 mm2/s) and normal parenchyma (1.59 ± 0.27 × 10−5 mm2/s) was detected (P < 0.0001). There were no correlations between the ADC value and prognostic factors. However, the median ADC value was lower in the ER‐positive group than the ER negative group, and this difference was marginally significant (1.09 × 10−5 mm2/s versus 1.15 × 10−5 mm2/s, P = 0.053).

Conclusion

The ADC value was a helpful parameter in detecting malignant breast tumors, but ADC value could not predict patient prognosis. J. Magn. Reson. Imaging 2009;30:615–620. © 2009 Wiley‐Liss, Inc.
Pre‐ and postoperative MR brain imaging with automatic planning and scanning software in tumor patients: An intraindividual comparative study at 3 Tesla
Authors: Nelles Michael , Gieseke Juergen , Urbach Horst , Semrau Renate , Bystrov Daniel , Schild Hans H. , Willinek Winfried A.
Published: August 2009

Purpose

To evaluate the feasibility of automatic planning and scanning of brain MR imaging (MRI) protocols on a clinical 3 Tesla system in tumor patients before and after neurosurgical intervention.

Materials and Methods

Twenty‐nine patients with intra‐axial lesions were examined with automated planscan software pre‐ and postoperatively. MR section geometries were determined using intensity‐based three‐dimensional registration and an extraction of landmarks. The technique involved an active shape model to match the boundaries of anatomical structures and typical shape variations. Insufficient geometries were corrected manually by a trained operator.

Results

In 29/29 of the preoperative and 47/58 MRI sessions in total, no manual interaction was necessary. Predominantly minor corrections were necessary in 11/29 postoperative sessions, with critical corrections (≥ 3‐mm offcenter change or ≥ 5° in alignment of the stacks) in 3/58 sessions. Mean offcenter correction was 1.41 mm (range, 0–7.33 mm), mean angle change toward the midline or commissural line was 1.43° (range, 0–8.05°).

Conclusion

Automatic planning and scanning before and after brain surgery yields robust results in most of the patients with substantial shape deviations. The dimensions of necessary geometry corrections are predominantly small. These results are promising to minimize interscan variability in longitudinal studies. J. Magn. Reson. Imaging 2009;30:672–677. © 2009 Wiley‐Liss, Inc.
An analysis of cloud observations from Vernadsky, Antarctica
Authors: Kirchgäßner Amélie
Published: August 2009

This paper presents results of a combined analysis of cloud observations made at the Antarctic base Faraday/Vernadsky between 1960 and 2005 and sea ice concentration from the HadISST1 data set.

The annual total cloud cover has increased significantly during this period with the strongest and most significant positive trend found in winter, and positive tendencies observable in all seasons. This trend is associated with a decrease in sea ice concentration in the area of the Western Antarctic Peninsula. Though the observed sea ice reduction is actually larger and more significant in summer and autumn, there is actually a significant relation between total cloud cover and sea ice concentration only in winter.

The increase in the total cloud cover is neither reflected in the low cloud amount nor in the number of records for low, medium or high level clouds. It is therefore thought that the increase in the total cloud cover is caused by an increase in the amount of medium and/or high level clouds. Instead, records for the low cloud amount show a redistribution from cases of extreme cloud cover (0, 1, 7 and 8 okta), which account for up to 90% of annual records, to cases of moderate cloud cover. In accordance with the decrease in sea ice, this may indicate a shift from low‐level stratiform towards convective clouds. Copyright © 2009 Royal Meteorological Society
Intercomparing multiple measures of the onset of spring in eastern North America
Authors: Schwartz Mark D. , Hanes Jonathan M.
Published: August 2009

Measuring the onset of deciduous tree leaf flush and subsequent development during the spring season in temperate climates can be accomplished using multiple ground and satellite‐based techniques. Although all these measurements are valid (i.e. record a real characteristic related to plant development), they typically are poorly inter‐related due to incompatible levels of spatial representation and differing methodologies. Given recent and likely future impacts of climate change on spring leaf development, the need to reconstruct past patterns, and the lack of standardised vegetation change measurements around the world, more work is needed to determine the relationships among the various measures, and the degree to which they may serve as substitutes for each other. In this article, we use observations and measurements at two phenology ‘super‐sites’ in eastern North America and four other supporting sites to evaluate the relationships among multiple spring leaf development measures, and explore strategies to standardise their intercomparison. The results show infrequent significant correlations among 10 satellite‐derived ‘start of season’ (SOS) measures (which suggests they are often not detecting the same phenomena), along with more common significant correlations among six ground phenology measures. However, when ground phenology and satellite‐derived SOS are compared, there are few significant correlations, even at sites with extensive native species phenology available. Modelled phenology, based on daily temperature data (Spring Indices First Bloom date) does as well as any of the direct native species measures, and is well suited to facilitate intercomparisons. In order to effectively compare ground‐based and satellite‐derived SOS measures, approaches that use limited numbers of individual plants face considerable challenges. Given that satellite‐derived measures are areal and at a scale of 250 m and larger, we suggest collecting ground phenology data at the same areal scale in order to make effective comparisons. Copyright © 2009 Royal Meteorological Society
Effects of platelet‐rich plasma on the quality of repair of mechanically induced core lesions in equine superficial digital flexor tendons: A placebo‐controlled experimental study
Authors: Bosch Gerco , van Schie Hans T. M. , de Groot Mark W. , Cadby Jennifer A. , van de Lest Chris H. A. , Barneveld Ab , van Weeren P. René
Published: August 2009

Tendon injuries are notorious for their slow and functionally inferior healing. Intratendinous application of platelet‐rich plasma (PRP) has been reported to stimulate the repair process of tendon injuries, but there is little conclusive evidence for its effectiveness. A placebo‐controlled experimental trial was performed to test the hypothesis that a single intratendinous PRP treatment enhances the quality of tendon repair, as evidenced by improved biochemical, biomechanical, and histological tissue properties. In six horses, tendon lesions were created surgically in the Superficial Digital Flexor Tendons (SDFT) of both front limbs, one of which was treated with PRP and the other with saline. After 24 weeks, the tendons were harvested for biochemical, biomechanical, and histological evaluations. Collagen, glycosaminoglycan, and DNA content (cellularity) was higher in PRP‐treated tendons (p = 0.039, 0.038, and 0.034, respectively). The repair tissue in the PRP group showed a higher strength at failure (p = 0.021) and Elastic Modulus (p = 0.019). Histologically, PRP‐treated tendons featured better organization of the collagen network (p = 0.031) and signs of increased metabolic activity (p = 0.031). It was concluded that PRP increases metabolic activity and seems to advance maturation of repair tissue over nontreated experimentally induced tendon lesions, which suggests that PRP might be beneficial in the treatment of clinical tendon injuries. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:211–217, 2010
Revolving hollow fiber–liquid phase microextraction coupled to GC/MS using electron ionization for quantification of five aromatic hydrocarbon isomers
Authors: Chen Yuan‐Chin , Wu Hui‐Fen
Published: August 2009

A dynamic liquid phase microextraction method using a revolving hollow fiber was demonstrated for coupling to GC/MS [using EI (electronic ionization) and selected ion monitor (SIM)] as a concentrating probe for rapid analysis and quantitative determination of five aromatic hydrocarbon isomers (cumene; propylbenzene; 2‐ethyltoluene; 1,2,3‐trimethylbenzene; and 1,2,4‐trimethylbenzene) from biological matrices (human urine and human plasma). This technique was named as revolving hollow fiber–liquid phase microextraction (RHF–LPME). The optimized parameters of RHF–LPME coupled to GC/MS experiments were extraction solvent, toluene; extraction time, 2 min; sample agitation rate, 700 rpm; salt concentration, 0%; rotating speed for motor driving rotator, 250 rpm; and the rotator was operated in a reversed direction with the stirrer. The linear range of calibration curve of RHF–LPME was from 0.002 to 0.4 μg/mL with R2 > 0.9916 and the RSD values were from 4.5 to 5.2%. Additionally, comparing to single drop microextraction (SDME), this method offers better limits of detection (LODs) and EF (enrichment factor). This approach exhibits many advantages including simplicity, rapid detection with high reproducibility and high extraction efficiency, easy to operate and fast to reach equilibrium for analyzing biological samples. This approach has the potential to be widely used because it only requires simple devices to perform all extraction processes. We believe that this technique can be a powerful tool for GC/MS analysis of biological samples and clinical applications in the near future.
Selective enrichment with “click oligo (ethylene glycol)” column and TOF–MS characterization of simple phenylpropanoids in the fruits of Forsythia suspensa
Authors: Wang Yaqin , Guo Zhimou , Jin Yu , Zhang Xiuli , Li Wei , Liang Xinmiao
Published: August 2009

To separate samples of complex natural products, highly efficient and selective separation methods should be developed. Herein, a selective enrichment method was developed to separate Forsythia suspensa components with “click oligo (ethylene glycol)” (OEG) column in reversed phase (RP) mode. In this method, F. suspensa aqueous extract was successfully separated. And three fractions with structure‐related compounds were obtained. Fraction I mainly consisted of C6–C2 natural alcohols and glycosides, fraction II mostly consisted of lignans, and fraction III mainly consisted of simple phenylpropanoids (SP). Then, the three fractions were separated with ultra‐performance liquid chromatography (UPLC). Four more lignans were observed in fraction II, and eight more SP were observed in fraction III than that without OEG column. Fraction III was successively characterized by TOF–MS, 2 acids (caffeic acid and chlorogenetic acid), 26 SP with caffeoyl, and 2 SP with coumaroyl were characterized. The results prove that a valid method has been developed to selectively enrich SP and lignans. And the method combined with UPLC can efficiently separate SP and lignans. Furthermore, the TOF–MS method is effective to confirm the substituents of SP.