bluuebunny/crossref_metadata_2025 huggingface dataset:
Use of high‐risk human papillomavirus testing in patients with low‐grade squamous intraepithelial lesions
Authors: Levi Angelique W. , Harigopal Malini , Hui Pei , Schofield Kevin , Chhieng David C.
Published: July 2011

BACKGROUND

The role of testing for high‐risk human papillomavirus (HR HPV) when triaging women with a cytologic diagnosis of low‐grade squamous intraepithelial lesion (LSIL) has not been well established. The objective of the current study was to correlate the status of HR HPV with the incidence of cervical intraepithelial neoplasia 2 and more severe lesions (CIN 2+) on tissue follow‐up in women with LSIL.

METHODS

A total of 1046 women with LSIL and HR HPV testing were identified in the database of a large teaching hospital within a 12‐month period. HR HPV testing was performed using the Hybrid Capture 2 assay with 1 relative light unit/cutoff as the cutoff.

RESULTS

Of the 1046 women with LSIL and concurrent HR HPV testing, 82.3% tested positive for HR HPV, 91.1% of whom were women aged < 30 years and 73% of whom were women aged ≥ 30 years (P < .001). Cytologic and/or histologic follow‐up was available in 979 (93.6%) women; 25.5% had negative follow‐up, 62.5% were found to have CIN 1 lesions, and 12.0% had CIN 2+ lesions. The sensitivity and negative predictive value of HR HPV status as a marker of CIN 2+ lesions were 98.3% and 98.9%, respectively. The colposcopy rate was 73.3% and 96.9% for women aged ≥ 30 years and women aged < 30 years, respectively (P = .01).

CONCLUSIONS

Using 1 RLU/CO as the cutoff value, HR HPV testing was found to be highly sensitive for detecting CIN 2+ lesions in women with LSIL. The colposcopy rate was significantly lower in women aged ≥ 30 years compared with women aged < 30 years. Triaging with HR HPV testing may be indicated in women aged ≥ 30 years with LSIL cytology, but not in women aged < 30 years. Cancer (Cancer Cytopathol) 2011;. © 2011 American Cancer Society.
Energy Conservative Solutions to a One‐Dimensional Full Variational Wave System
Authors: Zhang Ping , Zheng Yuxi
Published: July 2011

We establish the existence of a conservative weak solution to the initial value problem for a complete system of variational wave equations modeling liquid crystals in one space dimension, in which the director has two degrees of freedom. The solutions exist globally in time and singularities may develop in finite time, but the energy of the solutions is conserved across singular times. The method for existence also yields continuous dependence of solutions on the initial data. © 2011 Wiley Periodicals, Inc.
Atomic Ensemble Effects in Electrocatalysis: The Site‐Knockout Strategy
Authors: Cuesta Angel
Published: July 2011

During an electrocatalytic reaction bonds are broken and formed, and this requires that the reactants, the intermediates formed at the elementary reaction steps, and the products interact with a given number of surface atoms of the catalyst. Modifying the number of groups with an adequate number of surface atoms in a suitable geometric arrangement for a determined reaction step to proceed may affect the activity and/or selectivity of the catalyst. Although separating purely geometric atomic ensemble effects from electronic effects is not straightforward, the insights extracted from a detailed investigation of atomic ensemble effects can have a profound impact in the determination of electrocatalytic reaction mechanisms and in the design of more active and more selective electrocatalysts. This Minireview illustrates, using cyanide‐modified Pt(111) electrodes as an archetype, how eliminating only one kind of site from the surface (the site‐knockout strategy) by means of a regular array of inert adsorbates can be used to successfully study atomic ensemble effects in electrocatalysis. The possible consequences for the design of more efficient and more selective electrocatalysts are also commented on.
cis–trans Isomerisation of Substituted Aromatic Imines: A Comparative Experimental and Theoretical Study
Authors: Luo Ying , Utecht Manuel , Dokić Jadranka , Korchak Sergey , Vieth Hans‐Martin , Haag Rainer , Saalfrank Peter
Published: July 2011

The cis–trans isomerisation of N‐benzylideneaniline (NBA) and derivatives containing a central CN bond has been investigated experimentally and theoretically. Eight different NBA molecules in three different solvents were irradiated to enforce a photochemical trans${{\mathop \rightarrow \limits ^{h\nu }_{}}}$cis isomerisation and the kinetics of the thermal backreaction cis${{\mathop \rightarrow \limits ^{\Delta }_{}}}$trans were determined by NMR spectroscopy measurements in the temperature range between 193 and 288 K. Theoretical calculations using density functional theory and Eyring transition‐state theory were carried out for 12 different NBA species in the gas phase and three different solvents to compute thermal isomerisation rates of the thermal back reaction. While the computed absolute rates are too large, they reveal and explain experimental trends. Time‐dependent density functional theory provides optical spectra for vertical transitions and excitation energy differences between trans and cis forms. Together with isomerisation rates, the latter can be used to identify “optimal switches” with good photochromicity and reasonable thermal stability.
Carbon Nanotube Mass Production: Principles and Processes
Authors: Zhang Qiang , Huang Jia‐Qi , Zhao Meng‐Qiang , Qian Wei‐Zhong , Wei Fei
Published: July 2011

Our society requires new materials for a sustainable future, and carbon nanotubes (CNTs) are among the most important advanced materials. This Review describes the state‐of‐the‐art of CNT synthesis, with a focus on their mass‐production in industry. At the nanoscale, the production of CNTs involves the self‐assembly of carbon atoms into a one‐dimensional tubular structure. We describe how this synthesis can be achieved on the macroscopic scale in processes akin to the continuous tonne‐scale mass production of chemical products in the modern chemical industry. Our overview includes discussions on processing methods for high‐purity CNTs, and the handling of heat and mass transfer problems. Manufacturing strategies for agglomerated and aligned single‐/multiwalled CNTs are used as examples of the engineering science of CNT production, which includes an understanding of their growth mechanism, agglomeration mechanism, reactor design, and process intensification. We aim to provide guidelines for the production and commercialization of CNTs. Although CNTs can now be produced on the tonne scale, knowledge of the growth mechanism at the atomic scale, the relationship between CNT structure and application, and scale‐up of the production of CNTs with specific chirality are still inadequate. A multidisciplinary approach is a prerequisite for the sustainable development of the CNT industry.
Commentary on ‘Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD)’
Authors: Reiersen Angela M. , Handen Benjamin
Published: July 2011

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Williams K, Wheeler DM, Silove N, Hazell P. Selective serotonin reuptake inhibitors (SSRIs) for autism spectrum disorders (ASD). Cochrane Database of Systematic Reviews 2010, Issue 8. Art. No.: CD004677. DOI: 10.1002/14 651 858.CD004677.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Statins for children with familial hypercholesterolemia’
Authors: Editorial Office Evidence‐Based Child Health
Published: July 2011

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Vuorio A, Kuoppala J, Kovanen PT, Humphries SE, Strandberg T, Tonstad S, Gylling H. Statins for children with familial hypercholesterolemia. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD006401. DOI: 10.1002/14 651 858.CD006401.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentary on ‘Statins for children with familial hypercholesterolemia’
Authors: O'Gorman Clodagh S. M.
Published: July 2011

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Vuorio A, Kuoppala J, Kovanen PT, Humphries SE, Strandberg T, Tonstad S, Gylling H. Statins for children with familial hypercholesterolemia. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD006401. DOI: 10.1002/14 651 858.CD006401.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Non‐nutritive sucking for promoting physiologic stability and nutrition in preterm infants’
Authors: Editorial Office Evidence‐Based Child Health
Published: July 2011

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Pinelli J, Symington AJ. Non‐nutritive sucking for promoting physiologic stability and nutrition in preterm infants. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD001071. DOI: 10.1002/14 651 858. CD001071.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentaries on ‘Non‐nutritive sucking for promoting physiologic stability and nutrition in preterm infants’
Authors: Bingham Peter Matthias , Mathur Amit , Nyqvist Kerstin H. , Ewald Uwe
Published: July 2011

These are commentaries on a Cochrane review, published in this issue of EBCH, first published as: Pinelli J, Symington AJ. Non‐nutritive sucking for promoting physiologic stability and nutrition in preterm infants. Cochrane Database of Systematic Reviews 2005, Issue 4. Art. No.: CD001071. DOI: 10.1002/14 651 858.CD001071.pub2.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Intravenous immunoglobulin for Guillain‐Barré syndrome’
Authors: Editorial Office Evidence‐Based Child Health
Published: July 2011

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Hughes RAC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain‐Barré syndrome. Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No.: CD002063. DOI: 10.1002/14 651 858.CD002063.pub4. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Commentary on ‘Intravenous immunoglobulin for Guillain‐Barré syndrome’
Authors: Winer J. B.
Published: July 2011

This is a commentary on a Cochrane review, published in this issue of EBCH, first published as: Hughes RAC, Swan AV, van Doorn PA. Intravenous immunoglobulin for Guillain‐Barré syndrome. Cochrane Database of Systematic Reviews 2010, Issue 6. Art. No.: CD002063. DOI: 10.1002/14 651 858.CD002063.pub4.

Further information for this Cochrane review is available in this issue of EBCH in the accompanying Summary article. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Summary of ‘Nutritional support in children and young people with cancer undergoing chemotherapy’
Authors: Editorial Office Evidence‐Based Child Health
Published: July 2011

This is a summary of a Cochrane review, published in this issue of EBCH, first published as: Jones L, Watling RM, Wilkins S, Pizer B. Nutritional support in children and young people with cancer undergoing chemotherapy. Cochrane Database of Systematic Reviews 2010, Issue 7. Art. No.: CD003298. DOI: 10.1002/14 651 858.CD003298.pub2. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Caring for a Difficult Patient with Sore Throat
Authors: Moja Lorenzo , Bruschettini Matteo
Published: July 2011

This Dr Cochrane clinical vignette is based on upon an Overview of Cochrane Reviews that was published in a previous issue of Evidence‐Based Child Health: Foisy M, Martin B, Domino F, Becker, L A. The Cochrane Library and the Treatment of Sore Throat in Children and Adolescents: An Overview of Reviews. Evid‐Based Child Health 2011, 6: 6(3): 810–823; and inspired by: Marcy SM. When a parent insists on antibiotics for a virus. Am Fam Physician 1999; 59(3): 687–688.

Dr Cochrane is a unique self‐learning experience—the integration of Cochrane evidence with a quirky fictional story and multiple‐choice questions provides readers with the opportunity to explore and understand the applicability of a Cochrane Review or Overview in a new way.

In this series of fictional clinical vignettes, Dr Cochrane travels across time from the past century to the present day, to solve clinical problems using evidence from Cochrane Reviews. Read the associated article and then test your knowledge with five multiple‐choice questions. You can find the answers to the questions on page 1316. Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Caring for a Difficult Patient with Sore Throat
Authors: Moja Lorenzo , Bruschettini Matteo
Published: July 2011

These are the answers to the Dr Cochrane vignette on pages 1024–1026. How did you get on? Register your score at ebch@wiley.com Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. The Cochrane Collaboration
Fragility analysis of low‐rise masonry in‐filled reinforced concrete buildings by a coefficient‐based spectral acceleration method
Authors: Lee Chien‐Liang , Su Ray Kai Leung
Published: July 2011

This study presents a seismic fragility analysis of low‐rise masonry in‐filled (MI) reinforced concrete (RC) buildings using a proposed coefficient‐based spectral acceleration method. The coefficient‐based method, without requiring any complicated finite element analysis, is a simplified procedure for assessing the spectral acceleration demand (or capacity) of buildings subjected to earthquakes. This paper begins with a calibration of the proposed coefficient‐based method for low‐rise MI RC buildings using published experimental results obtained from shaking table tests. Spectral acceleration‐based fragility curves for low‐rise MI RC buildings under various inter‐story drift limits are then constructed using the calibrated coefficient‐based method. A comparison of the experimental and estimated results indicates that the simplified coefficient‐based method can provide good approximations of the spectral accelerations at peak loads of low‐rise MI RC buildings, if a proper set of drift‐related factors and initial fundamental periods of structures are used. Moreover, the fragility curves constructed using the coefficient‐based method can provide a satisfactory vulnerability evaluation for low‐rise MI RC buildings under a given performance level. Copyright © 2011 John Wiley & Sons, Ltd.
Occurrence and endocrine effects of agrichemicals in a small Nebraska, USA, watershed
Authors: Sellin Jeffries Marlo K , Abbott Kelty I , Cowman Tim , Kolok Alan S
Published: July 2011

The Bow Creek watershed (Nebraska, USA) is dominated by the production of beef cattle and row crops; therefore, surface waters are likely to receive runoff containing steroid hormones and pesticides. The goal of the present study was to determine the occurrence and endocrine effects of agrichemicals in this watershed. To accomplish this, four sites within the watershed—Pearl, Bow, and East Bow Creeks and a site at the confluence with the Missouri River—were selected. In June of 2008, polar organic chemical integrative samplers (POCIS) were deployed at each site, whereas in June of 2009, water and sediment samples were collected. Caged fathead minnows (Pimephales promelas) were deployed at all of the selected sites in both years. Analysis of these samples revealed that steroid hormones were not present; however, pesticides were present in POCIS extracts and water samples. In general, the amount of pesticides was higher in POCIS retrieved from Pearl and Bow Creeks than in POCIS from East Bow Creek and the confluence. This variation between sites appeared to be related to row crop density, as row crop land cover surrounding the Pearl and Bow Creek sites was higher than that surrounding the East Bow and confluence sites. To determine the endocrine effects of agrichemicals within this watershed, the hepatic mRNA expression of vitellogenin and estrogen receptor α (ERα), as well as the gonadal expression of P450 aromatase A, was determined for the caged minnows. Females deployed at East Bow Creek and the confluence experienced decreases in the expression of ERα, suggesting that these females had been defeminized; however, this defeminization could not be attributed to any of the pesticides detected at these sites. Environ. Toxicol. Chem. 2011;30:2253–2260. © 2011 SETAC
Archaean granulite facies metamorphism at the Singhbhum Craton–Eastern Ghats Mobile Belt interface: implication for the Ur supercontinent assembly
Authors: Mahapatro S. N. , Pant N. C. , Bhowmik S. K. , Tripathy A. K. , Nanda J. K.
Published: July 2011

In this study, we investigate the geological significance and the antiquity of lower crustal granulite facies metamorphism from the Rengali Domain, which lies in between the Singhbhum Craton in the north and the Eastern Ghats Mobile Belt in the south. Petrographic, mineral compositional, metamorphic reaction history and geothermobarometric studies of two representative metapelite granulite samples reveal widespread biotite melting at peak granulite facies metamorphic conditions of 7.8 ± 0.13 kbar, 849 ± 31 °C and subsequent melt extraction, producing a mixture of residual granulites and melts in the Rengali Province. Depending on local bulk rock compositional variations, biotite melting produced peak metamorphic assemblages of garnet + cordierite in the more aluminous compositional domain, while garnet + orthopyroxene + cordierite resulted in domains of intermediate alumina. During post‐peak cooling, there were localized developments of biotite + sillimanite + quartz symplectites replacing garnet and cordierite and biotite + quartz intergrowths after orthopyroxene. Application of garnet‐orthopyroxene and garnet‐biotite Fe–Mg exchange thermometers to co‐existing garnet rim and symplectitic biotite show the extent of cooling to 610–660 °C. Electron microprobe geochronology of texturally well constrained monazites indicates the timing of peak granulite metamorphism at 3057 ± 17 Ma and its metamorphic reheating at 2781 ± 16 Ma. The present findings when collated with available geological and geophysical data appear to indicate that the studied granulites and the associated granite gneisses, charnockite and enderbite suite of rocks of the Rengali Domain are part of the exhumed lower continental crust of the Singhbhum Craton. The significance of this Neoarchaean orogenesis in the ‘Ur’ supercontinent assembly is discussed. Copyright © 2011 John Wiley & Sons, Ltd.
Two‐year effects of an interdisciplinary intervention on recovery following hip fracture in older Taiwanese with cognitive impairment
Authors: Shyu Yea‐Ing L. , Tsai Wen‐Che , Chen Min‐Chi , Liang Jersey , Cheng Huey‐Shinn , Wu Chi‐Chuan , Su Juin‐Yih , Chou Shih‐Wei
Published: July 2011

Objective

This article aims to evaluate the long‐term effects of an interdisciplinary intervention program on cognitively impaired older persons after hip fracture in Taiwan.

Methods

Of 160 subjects randomly assigned to control (n = 81) and intervention (n = 79) groups, 24 (29.6%) and 27 (34.2%) were cognitively impaired in the control and intervention groups, respectively, and outcomes were followed for 2 years after discharge.

Results

Among cognitively impaired subjects, more in the intervention group recovered their previous walking ability (odds ratio [OR] = 3.49; confidence interval [CI] = 1.64 to 7.42), activities of daily life performance (β = 18.59; p = 0.0002), and more were readmitted to the hospital (OR = 4.44, CI = 1.53 to 12.89) than those in the control group during the first 2 years following discharge. Among subjects without cognitive impairment, more in the intervention group recovered their previous walking ability (OR = 2.6; CI = 1.33 to 5.07), had fewer falls (OR = 0.47; CI = 0.25 to 0.86), and made fewer emergency room visits (OR = 0.33; CI = 0.11 to 0.97) during the first 2 years following discharge than those in the control group.

Conclusions

Cognitively impaired individuals benefited from our interdisciplinary intervention by improving their walking ability and physical function during the first 2 years following discharge. Specific strategies on fall prevention following hip fracture need to be further developed for cognitively impaired individuals. Copyright © 2011 John Wiley & Sons, Ltd.
Urinary acylcarnitines are altered in human kidney cancer
Authors: Ganti Sheila , Taylor Sandra L. , Kim Kyoungmi , Hoppel Charles L. , Guo Lining , Yang Joy , Evans Christopher , Weiss Robert H.
Published: July 2011

Kidney cancer often diagnosed at late stages when treatment options are severely limited. Thus, greater understanding of tumor metabolism leading ultimately to novel approaches to diagnosis is needed. Our laboratory has been utilizing metabolomics to evaluate compounds appearing in kidney cancer patients' biofluids at concentrations different from control patients. Here, we collected urine samples from kidney cancer patients and analyzed them by chromatography coupled to mass spectrometry. Once normalized to control for urinary concentration, samples were analyzed by two independent laboratories. After technical validation, we now show differential urinary concentrations of several acylcarnitines as a function of both cancer status and kidney cancer grade, with most acylcarnitines being increased in the urine of cancer patients and in those patients with high cancer grades. This finding was validated in a mouse xenograft model of human kidney cancer. Biological validation shows carbon chain length‐dependent effects of the acylcarnitines on cytotoxicity in vitro, and higher chain length acylcarnitines demonstrated inhibitory effects on NF‐κB activation, suggesting an immune modulatory effect of these compounds. Thus, acylcarnitines in the kidney cancer urine may reflect alterations in metabolism, cell component synthesis and/or immune surveillance, and may help explain the profound chemotherapy resistance seen with this cancer. This study shows for the first time the value of a novel class of metabolites which may lead to new therapeutic approaches for cancer and may prove useful in cancer biomarker studies. Furthermore, these findings open up a new area of investigation into the metabolic basis of kidney cancer.
Biomarkers predicting development of metachronous gastric cancer after endoscopic resection: an analysis of molecular pathology of Helicobacter pylori eradication
Authors: Watari Jiro , Moriichi , Kentaro , Tanabe , Hiroki , Kashima Shin , Nomura Yoshiki , Fujiya Mikihiro , Tomita Toshihiko , Oshima Tadayuki , Fukui Hirokazu , Miwa Hiroto , Das Kiron M. , Kohgo Yutaka
Published: July 2011

Metachronous gastric cancer (MGC) after endoscopic resection (ER) of gastric cancer still occurs to some degree even after Helicobacter pylori (H. pylori) treatment. We evaluated whether two biomarkers related to carcinogenesis expressed in intestinal metaplasia (IM) become predictors for MGC development after eradication. We performed a hospital‐based, case–control study of 75 patients, including 50 mucosal cancer patients who had undergone ER (Group DYS), and 25 age‐ and sex‐matched chronic gastritis patients for whom H. pylori had been successfully eradicated (control). Additionally, Group DYS patients were divided into two groups: 25 successfully H. pylori‐eradicated (eradicated group) and 25 un‐eradicated patients (persistent group). All patients were followed for 1 year. We analyzed microsatellite instability (MSI) and immunoperoxidase assays using a monoclonal antibody for the colonic phenotype (Das‐1). Both MSI and Das‐1 reactivity in IM were significantly higher in Group DYS than in the control (p < 0.05 and p < 0.01, respectively). MSI and Das‐1 reactivity were strong and independent predictors for gastric cancer (OR = 7.09, 95% CI 1.27–39.6, p = 0.03 for MSI and OR = 4.96, 95% CI 1.64–15.0, p = 0.005 for Das‐1 reactivity). The incidence of MSI tended to decrease in the eradicated group (p = 0.07), but not in the persistent group. The Das‐1 immunoreactivity in IM also declined in both the eradicated group and the control. Interestingly, all MGCs after ER were positive for MSI or Das‐1 reactivity. MSI or Das‐1 reactivity in IM strongly predicts the development of MGC. Patients in whom these biomarkers persist after eradication may therefore have a high risk of developing MGC.
ETS‐1/RhoC signaling regulates the transcription factor c‐Jun in melanoma
Authors: Spangler Barbara , Kappelmann Melanie , Schittek Birgit , Meierjohann Svenja , Vardimon Lily , Bosserhoff Anja Katrin , Kuphal Silke
Published: July 2011

Recently, we discovered that the loss of E‐cadherin induces c‐Jun protein expression, which is a member of the AP‐1 transcription factor family and a key player in the processes of cell proliferation and tumor development and also found in elevated levels in melanomas. Notably, the mRNA level of c‐Jun was not affected, suggesting that c‐Jun is regulated at post‐transcriptional level. Here, we present data that suggest that the dynamic cytoskeletal network, linked to E‐cadherin, is involved in the regulation of the c‐Jun protein and transcriptional activity. In a signaling cascade, the loss of E‐cadherin activates the transcriptional regulator ETS‐1 and consequently leads to the induction of RhoC expression that stabilizes c‐Jun in melanoma. The link between RhoC and c‐Jun seems to be indirect via the cytoskeleton. We conclude that the loss of E‐cadherin mediated cell‐adhesion induces c‐Jun protein expression in a multistep process, offering several possibilities for therapeutic intervention.
Human adipose tissue‐derived mesenchymal stem cells expressing yeast cytosinedeaminase::uracil phosphoribosyltransferase inhibit intracerebral rat glioblastoma
Authors: Altanerova Veronika , Cihova Marina , Babic Michal , Rychly Boris , Ondicova Katarina , Mravec Boris , Altaner Cestmir
Published: July 2011

Prodrug cancer gene therapy by mesenchymal stem cells (MSCs) targeted to tumors represents an attractive tool to activate prodrugs directly within the tumor mass, thus avoiding systemic toxicity. In this study, we tested the feasibility and efficacy of human adipose tissue‐derived MSCs, engineered to express the suicide gene cytosine deaminase::uracil phosphoribosyltransferase to treat intracranial rat C6 glioblastoma. Experiments were designed to simulate conditions of future clinical application for high‐grade glioblastoma therapy by direct injections of therapeutic stem cells into tumor. We demonstrated that genetically modified therapeutic stem cells still have the tumor tropism when injected to a distant intracranial site and effectively inhibited glioblastoma growth after 5‐fluorocytosine (5‐FC) therapy. Coadministration of C6 cells and therapeutic stem cells with delayed 5‐FC therapy improved the survival in a therapeutic stem cell dose‐dependent manner and induced complete tumor regression in a significant number of animals. Continuous intracerebroventricular delivery of 5‐FC using osmotic pump reduced the dose of prodrug required for the same therapeutic effect, and along with repeated administration of therapeutic stem cells increased the survival time. Intracerebral injection of therapeutic stem cells and treatment with 5‐FC did not show any detectable adverse effects. Results support the arguments to begin clinical studies for treatment of high‐grade brain tumors.
Inecalcitol, an analog of 1α,25(OH)2D3, induces growth arrest of androgen‐dependent prostate cancer cells
Authors: Okamoto Ryoko , Delansorne Remi , Wakimoto Naoki , Doan Ngan B. , Akagi Tadayuki , Shen Michelle , Ho Quoc H. , Said Jonathan W. , Koeffler H. Phillip
Published: July 2011

19‐nor‐14‐epi‐23‐yne‐1,25(OH)2D3 (inecalcitol) is a unique vitamin D3 analog. We evaluated the activity of inecalcitol in a human prostate cancer model system. The analog was 11‐fold more potent than 1,25(OH)2D3 in causing 50% clonal growth inhibition of androgen‐sensitive human prostate cancer LNCaP cells. Inecalcitol, more than 1,25(OH)2D3, reduced in a dose‐dependent manner the expression levels of the transcription factor ETS variant 1 and the serine/threonine protein kinase Pim‐1, both of which are upregulated in prostate cancer. Remarkably, dose challenge experiments revealed that inecalcitol maximal tolerated dose (MTD) by intraperitoneal (i.p.) administration was 30 μg/mouse (1,300 μg/kg) three times per week, while we previously found that the MTD of 1,25(OH)2D3 is 0.0625 μg/mouse; therefore, inecalcitol is 480 times less hypercalcemic than 1,25(OH)2D3. Pharmacokinetic studies showed that plasma half‐life of inecalcitol were 18.3 min in mice. A xenograft model of LNCaP cells was developed in immunodeficient mice treated with inecalcitol. The tumors of the diluent‐treated control mice increased in size but those in the inecalcitol treatment group did not grow. Our data suggest that inecalcitol inhibits androgen‐responsive prostate cancer growth in vivo and should be examined either alone or with other chemotherapy in clinical trials in individuals with rising serum prostate‐specific antigen after receiving either surgery or irradiation therapy with curative intent.
In vitro biodegradation behavior of magnesium and magnesium alloy
Authors: Wang Hao , Shi Zhiming
Published: July 2011

Magnesium has the potential to be used as degradable metallic biomaterial. For magnesium and its alloys to be used as biodegradable implant materials, their degradation rates should be consistent with the rate of healing of the affected tissue, and the release of the degradation products should be within the body's acceptable absorption levels. Conventional magnesium degrades rapidly, which is undesirable. In this study, biodegradation behaviors of high purity magnesium and commercial purity magnesium alloy AZ31 in both static and dynamic Hank's solution are systematically investigated. The in vitro test results show that magnesium purification and selective alloying are effective approaches to reduce the degradation rate of magnesium. In the static condition, the corrosion products accumulate on the materials surface as a protective layer, which results in a lower degradation rate than the dynamic condition. Anodized coating can significantly further reduce the degradation rate of magnesium. This study strongly indicates that magnesium can be used as degradable implant material as long as the degradation is controlled at a low rate. Magnesium purification, selective alloying, and anodized coating are three effective approaches to reduce the rate of degradation. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2011.
An in vitro correlation of metastatic capacity, substrate rigidity, and ECM composition
Authors: Indra Indrajyoti , Beningo Karen A.
Published: July 2011

The process of metastasis requires a metastatic cancer cell to invade a variety of micro‐environments of variable stiffnesses. Unlike metastatic cells, normal cell function and viability is dependent on the stiffness of the environment and used as a cue to maintain cell health and proper tissue organization. In this study we have asked if metastatic cells can ignore the parameter of stiffness and if this ability is gradually acquired and if so, through what mechanism. Using a panel of mouse mammary tumor cells derived from the same parental tumor, but possessing different metastatic abilities, we cultured the cells on hard and soft substrates conjugated with collagen or fibronectin. Normal and non‐metastatic tumor cells responded to changes in stiffness on fibronectin, but not collagen. However, the more metastatic cells ignored the change in stiffness on fibronectin‐coated substrates. This lack of response on fibronectin correlated with a change in the expression level of the α3 integrin subunit, activation of the β1 subunit, and phosphorylation of FAKpY397. We conclude that through fibronectin, changes in the activation and tethering of the beta‐1 integrin provides a mechanism for metastatic cells to disregard changes in compliance to survive and navigate in environments of different stiffness. J. Cell. Biochem. 112: 3151–3158, 2011. © 2011 Wiley Periodicals, Inc.
Curcumin protects against ovariectomy‐induced bone loss and decreases osteoclastogenesis
Authors: Kim W.K. , Ke K. , Sul O.J. , Kim H.J. , Kim S.H. , Lee M.H. , Kim H.J. , Kim S.Y. , Chung H.T. , Choi H.S.
Published: July 2011

Curcumin has anti‐oxidative activity. In view of the increasing evidence for a biochemical link between increased oxidative stress and reduced bone density we hypothesized that curcumin might increase bone density by elevating antioxidant activity in some target cell type. We measured bone density by Micro‐CT, enzyme expression levels by quantitative PCR or enzyme activity, and osteoclast (OC) formation by tartrate‐resistant acid phosphatase staining. The bone mineral density of the femurs of curcumin‐administered mice was significantly higher than that of vehicle‐treated mice after ovariectomy (OVX) and this was accompanied by reduced amounts of serum collagen‐type I fragments, which are markers of bone resorption. Curcumin suppressed OC formation by increasing receptor activator of nuclear factor‐κB ligand (RANKL)‐induced glutathione peroxidase‐1, and reversed the stimulatory effect of homocysteine, a known H2O2generator, on OC formation by restoring Gpx activity. Curcumin generated an aberrant RANKL signal characterized by reduced expression of nuclear factor of activated T cells 2 (NFAT2) and attenuated activation of mitogen‐activated protein kinases (ERK, JNK, and p38). Curcumin thus inhibited OVX‐induced bone loss, at least in part by reducing osteoclastogenesis as a result of increased antioxidant activity and impaired RANKL signaling. These findings suggest that bone loss associated with estrogen deficiency could be attenuated by curcumin administration. J. Cell. Biochem. 112: 3159–3166, 2011. © 2011 Wiley Periodicals, Inc.
PI3K/Akt responses to oxytocin stimulation in Caco2BB gut cells
Authors: Klein Benjamin Y. , Tamir Hadassah , Welch Martha G.
Published: July 2011

Recently, we discovered oxytocin receptor (OTR) expression in the developing gut villus epithelium that emerges in villus–crypt junctions after weaning. Oxytocin (OT) and OTR regulate many physiological functions in various tissues; however, their function in gut epithelium is unknown. We explored responses of PI3K and Akt phosphoisoforms to OT stimuli in the Caco2BB human gut cell line. In Caco2BB cells, PI3K and pAkt levels peaked at 62.5 nM OT. At higher concentrations, PI3K decreased more gradually than pAktS473 suggesting that the pAktS473 response is separate from PI3K. At ≤7.8 nM OT, pAktT308 increased while pAktS473 decreased. Using a specific OTR antagonist, we demonstrated that responses of pAktT308 to OT depend on OTR in contrast to the partial OTR‐dependence of the pAktS473 response. Differential pAkt phosphoisoform responses included pAkt phosphoserine 473 persistently free of phosphothreonine 308. The reduction in PI3K after 62.5 nM OT for 30 min coincided with OTR internalization. The PI3K/Akt activation profile was somewhat different in other cell lines (MCF‐7 breast cancer cells, HT29 gut cells), which have PI3K activating mutations, that were examined to establish experimental parameters. In Caco2BB cells, the divergent effects of OT upon pAkt phosphoisoforms suggests separate sub‐pathways; pAkt T308 activation depends on OTR via the PI3K pathway and pAktS473 presumably results from its specific kinase mTORC2 (mammalian target of rapamycin complex 2). Thus, OT may modulate gut cell functions downstream of mTOR complexes (e.g., translation control as suggested by others in uterine cells). We will next explore OT‐stimulated kinase activities downstream of mTOR related to pAkt phosphoisoforms. J. Cell. Biochem. 112: 3216–3226, 2011. © 2011 Wiley Periodicals, Inc.
Effect of dual‐specificity protein phosphatase 5 on pluripotency maintenance and differentiation of mouse embryonic stem cells
Authors: Chen Qi , Zhou Yang , Zhao Xiaoli , Zhang Ming
Published: July 2011

The MAPK/Erk signaling pathway is considered as a key regulator of the pluripotency and differentiation of embryonic stem (ES) cells, while dual‐specificity protein phosphatases (DUSPs) are negative regulators of MAPK. Although DUSPs are potential embryogenesis regulators, their functions in the regulation of ES cell differentiation have not been demonstrated. The present study revealed that Dusp5 was expressed in mouse ES (mES) cells and that its expression was correlated with the undifferentiated state of these cells. Exogenous Dusp5 expression enhanced mES cell clonogenicity and suppressed mES cell differentiation by maintaining Nanog expression via the inhibition of the Erk pathway. Following Dusp5 knockdown, Nanog and Oct4 expression was significantly attenuated and the Erk signaling pathway was activated. Additionally, EBs derived from Dusp5 knockdown mES cells (KDEBs) exhibited a weak adherence capability, very little outgrowth, and a reduction in the number of epithelial‐like cells. The expression of Gata6 (an endodermal marker) and Flk1 and Twist1 (mesodermal markers) was inhibited in KDEBs, which indicated that Dusp5 influenced the differentiation of these germ layers during EB development. Collectively, this study suggested that Dusp5 plays an important role in the maintenance of pluripotency in mES cells, and that Dusp5 may be required for EB development. J. Cell. Biochem. 112: 3185–3193, 2011. © 2011 Wiley Periodicals, Inc.
Resolution of inflammation by N‐arachidonoylglycine
Authors: Burstein Sumner H. , McQuain Catherine A. , Ross Alonzo H. , Salmonsen Rebecca A. , Zurier Robert E.
Published: July 2011

N‐arachidonoylglycine (NAgly) is an endogenous signaling lipid that is a member of the eicosanoid super family and is related to anandamide. It shows anti‐inflammatory activity in vivo in the mouse peritonitis model where it reduces migration of inflammatory leukocytes following injection of pro‐inflammatory agents into the peritoneal cavity. Using cell culture models, including GPR18 transfected HEK‐293 cells, evidence is presented that the orphan receptor GPR18 is involved in this action. Increases in free arachidonic acid, and robust stimulation of anti‐inflammatory eicosanoids were observed at low micromolar concentrations. These included 15‐deoxy‐delta‐13,14‐PGJ2 and lipoxin A4 both of which are believed to mediate the resolution stage of inflammation. It was further shown that NAgly might act via GPR18 activation in promoting the number of Trypan Blue stained cells, a possible indicator of programmed cell death. Thus, we hypothesize that NAgly induces the death of inflammatory cells, a process that is considered to be important for the resolution of inflammation. J. Cell. Biochem. 112: 3227–3233, 2011. © 2011 Wiley Periodicals, Inc.
Deregulated HOX genes in ameloblastomas are located in physical contiguity to keratin genes
Authors: Schiavo Giulia , D'Antò Vincenzo , Cantile Monica , Procino Alfredo , Di Giovanni Stefano , Valletta Rossella , Terracciano Luigi , Baumhoer Daniel , Jundt Gernot , Cillo Clemente
Published: July 2011

The expression of the HOX gene network in mid‐stage human tooth development mostly concerns the epithelial tooth germ compartment and involves the C and D HOX loci. To further dissect the HOX gene implication with tooth epithelium differentiation we compared the expression of the whole HOX network in human ameloblastomas, as paradigm of epithelial odontogenic tumors, with tooth germs. We identified two ameloblastoma molecular types with respectively low and high number of active HOX C genes. The highly expressing HOX C gene ameloblastomas were characterized by a strong keratinized phenotype. Locus C HOX genes are located on chromosome 12q13–15 in physical contiguity with one of the two keratin gene clusters included in the human genome. The most posterior HOX C gene, HOX C13, is capable to interact with hair keratin genes located on the other keratin gene cluster in physical contiguity with the HOX B locus on chromosome 17q21–22. Inside the HOX C locus, a 2.2 kb ncRNA (HOTAIR) able to repress transcription, in cis, along the entire HOX C locus and, in trans, at the posterior region of the HOX D locus has recently been identified. Interestingly both loci are deregulated in ameloblastomas. Our finding support an important role of the HOX network in characterizing the epithelial tooth compartment. Furthermore, the physical contiguity between locus C HOX and keratin genes in normal tooth epithelium and their deregulation in the neoplastic counterparts suggest they may act on the same mechanism potentially involved with epithelial tumorigenesis. J. Cell. Biochem. 112: 3206–3215, 2011. © 2011 Wiley Periodicals, Inc.
Identification of specific nuclear structural protein alterations in human breast cancer
Authors: Debald Manuel , Franken Sebastian , Heukamp Lukas Carl , Linke Andrea , Wolfgarten Matthias , Walgenbach Klaus‐Jürgen , Braun Michael , Rudlowski Christian , Gieselmann Volkmar , Kuhn Walther , Hartmann Gunther , Walgenbach‐Brünagel Gisela
Published: July 2011

Breast cancer is the most commonly diagnosed type of cancer and a major cause of death in women. Reliable biomarkers are urgently needed to improve early detection or to provide evidence of the prognosis for each individual patient through expression levels in tumor tissue or body fluids. This proteomic analysis focused on the nuclear structure of human breast cancer tissue, which has been shown to be a promising tool for cancer biomarker development. The nuclear matrix composition of human breast cancer (n = 14), benign controls (n = 2), and healthy controls (n = 2) was analyzed by high‐resolution two‐dimensional gel electrophoresis and mass spectrometry. Validation studies were performed in an individual sample set consisting of additional breast cancer tissues (n = 3) and additional healthy control tissues (n = 2) by one‐dimensional immunoblot. In this setting, we identified five proteins that were upregulated in human breast cancer tissue, but absent in the healthy and benign controls (P < 0.001). These spots were also present in the investigated human breast cancer cell lines, but absent in the MCF10a cell line, which represents normal human epithelial breast cells. Two of the breast cancer‐specific proteins have been confirmed to be calponin h2 and calmodulin‐like protein 5 by one‐dimensional immunoblot. This is the first study demonstrating the expression of both proteins in human breast cancer tissue. Further studies are required to investigate the potential role of these proteins as biomarkers for early diagnosis or prognosis in human breast cancer. J. Cell. Biochem. 112: 3176–3184, 2011. © 2011 Wiley Periodicals, Inc.
Computational protocols for prediction of solute NMR relative chemical shifts. A case study of L‐tryptophan in aqueous solution
Authors: Eriksen Janus J. , Olsen Jógvan Magnus H. , Aidas Kȩstutis , Ågren Hans , Mikkelsen Kurt V. , Kongsted Jacob
Published: July 2011

In this study, we have applied two different spanning protocols for obtaining the molecular conformations of L‐tryptophan in aqueous solution, namely a molecular dynamics simulation and a molecular mechanics conformational search with subsequent geometry re‐optimization of the stable conformers using a quantum mechanically based method. These spanning protocols represent standard ways of obtaining a set of conformations on which NMR calculations may be performed. The results stemming from the solute–solvent configurations extracted from the MD simulation at 300 K are found to be inferior to the results stemming from the conformations extracted from the MM conformational search in terms of replicating an experimental reference as well as in achieving the correct sequence of the NMR relative chemical shifts of L‐tryptophan in aqueous solution. We find this to be due to missing conformations visited during the molecular dynamics run as well as inaccuracies in geometrical parameters generated from the classical molecular dynamics simulations. © 2011 Wiley Periodicals, Inc. J Comput Chem, 2011
Setting up suicide prevention plans at the local level: the methodology of focus groups with stakeholders
Authors: Poma Stefano Zanone , Grossi Antonello , Venturini Monica , Cristina Contessa , Toniolo Emanuele
Published: July 2011

In the prevention of suicide, there is a need to transform clinical studies into health promotion by a cooperation with territorial agencies. A survey on a group of stakeholders was performed with the methodology of focus group. The evaluation criteria used by the participants were practical and not methodological and were closely linked to the stakeholders' point of view. High importance was given to building a network in the territory and some indications came out for each target group (e.g., interventions in schools for adolescents). In conclusion, a qualitative survey on the stakeholders' opinion is useful, but it needs a steering that integrates the different points of view and joins them with methodological requirements and funds availability. © 2011 Wiley Periodicals, Inc.
The development and feasibility of a brief risk reduction intervention for newly HIV‐diagnosed men who have sex with men
Authors: Sikkema Kathleen J. , Hansen Nathan B. , Kochman Arlene , Santos Jonathan , Watt Melissa H. , Wilson Patrick A. , DeLorenzo Allyson , Laudato Jay , Mayer Gal
Published: July 2011

Men who have sex with men (MSM) represent more than half of all new HIV infections in the United States. Utilizing a collaborative, community‐based approach, a brief risk reduction intervention was developed and pilot tested among newly HIV‐diagnosed MSM receiving HIV care in a primary care setting. Sixty‐five men, within 3 months of diagnosis, were randomly assigned to the experimental condition or control condition and assessed at baseline, 3‐month, and 6‐month follow‐up. Effect sizes were calculated to explore differences between conditions and over time. Results demonstrated the potential effectiveness of the intervention in reducing risk behavior, improving mental health, and increasing use of ancillary services. Process evaluation data demonstrated the acceptability of the intervention to patients, clinic staff, and administration. The results provide evidence that a brief intervention can be successfully integrated into HIV care services for newly diagnosed MSM and should be evaluated for efficacy. © 2011 Wiley Periodicals, Inc.
Pathways to aggression in urban elementary school youth
Authors: Ozkol Hivren , Zucker Marla , Spinazzola Joseph
Published: July 2011

This study examined the pathways from violence exposure to aggressive behaviors in urban, elementary school youth. We utilized structural equation modeling to examine putative causal pathways between children's exposure to violence, development of posttraumatic stress symptoms, permissive attitudes towards violence, and engagement in aggressive behaviors. Self‐report measures were administered to 259 4th‐grade students from urban schools. Almost 100% of participants reported exposure to at least one experience with violence. Results demonstrated that both posttraumatic stress symptoms and attitudes toward violence mediated the relation between exposure to violence and aggression. This model suggests that the relation between violence exposure and youth violence and aggression is multidetermined, suggesting the need for both the developmental adaptation of tertiary prevention and intervention strategies so as to be suitable for younger children, as well as the need for multiple or multifaceted interventions. © 2011 Wiley Periodicals, Inc.