bluuebunny/crossref_metadata_2025 huggingface dataset:
Radioembolization with Yttrium-90 Glass Microspheres in Hepatocellular Carcinoma: European Experience on Safety and Long-Term Survival
Authors: Hilgard Philip , Hamami Monia , Fouly Amr El , Scherag André , Müller Stefan , Ertle Judith , Heusner Till , Cicinnati Vito R. , Paul Andreas , Bockisch Andreas , Gerken Guido , Antoch Gerald
Published: August 2010

Radioembolization has been demonstrated to allow locoregional therapy of patients with hepatocellular carcinoma not eligible for transarterial chemoembolization or other local therapies. The aim of this study was to validate evidence of the safety and efficacy of this treatment in a European sample of patients with advanced hepatocellular carcinoma (HCC). Therefore, 108 consecutive patients with advanced HCC and liver cirrhosis were included. Yttrium-90 (Y-90) microspheres were administered in a lobar fashion over the right or left branch of the hepatic artery. The response to treatment was evaluated by computed tomography (CT) imaging applying Response Evaluation Criteria in Solid Tumors (RECIST) and World Health Organization (WHO) criteria with recent European Association for the Study of the Liver / National Cancer Institute (EASL/NCI) amendments. Time to progression (TTP) and overall survival were estimated by the Kaplan-Meier method. In all, 159 treatment sessions were performed ranging between one to three treatments per patient. The mean radiation dose per treatment was 120 (±18) Gy. According to EASL criteria, complete responses were determined in 3% of patients, partial responses in 37%, stable disease 53%, and primary progression in 6% of patients. TTP was 10.0 months, whereas the median overall survival was 16.4 months. No lung or visceral toxicity was observed. The most frequently observed adverse events was a transient fatigue-syndrome.

Conclusion:

Radioembolization with Y-90 glass microspheres for patients with advanced HCC is a safe and effective treatment which can be utilized even in patients with compromised liver function. Because TTP and survival appear to be comparable to systemic therapy in selected patients with advanced HCC, randomized controlled trials in combination with systemic therapy are warranted. (Hepatology 2010;52:1741-1749)
Toward a knowledge infrastructure for traits-based ecological risk assessment
Authors: Baird Donald J , Baker Christopher J O , Brua Robert B , Hajibabaei Mehrdad , McNicol Kearon , Pascoe Timothy J , de Zwart Dick
Published: August 2010

The trait approach has already indicated significant potential as a tool in understanding natural variation among species in sensitivity to contaminants in the process of ecological risk assessment. However, to realize its full potential, a defined nomenclature for traits is urgently required, and significant effort is required to populate databases of species–trait relationships. Recently, there have been significant advances in the area of information management and discovery in the area of the semantic web. Combined with continuing progress in biological trait knowledge, these suggest that the time is right for a reevaluation of how trait information from divergent research traditions is collated and made available for end users in the field of environmental management. Although there has already been a great deal of work on traits, the information is scattered throughout databases, literature, and undiscovered sources. Further progress will require better leverage of this existing data and research to fill in the gaps. We review and discuss a number of technical and social challenges to bringing together existing information and moving toward a new, collaborative approach. Finally, we outline a path toward enhanced knowledge discovery within the traits domain space, showing that, by linking knowledge management infrastructure, semantic metadata (trait ontologies), and Web 2.0 and 3.0 technologies, we can begin to construct a dedicated platform for TERA science. Integr Environ Assess Manag 2011;7:209–215. © 2010 SETAC
Azacytidine impairs NK cell reactivity while decitabine augments NK cell responsiveness toward stimulation
Authors: Schmiedel Benjamin J. , Arélin Viktor , Gruenebach Frank , Krusch Matthias , Schmidt Susanne M. , Salih Helmut R.
Published: August 2010

Azacytidine and decitabine are approved for treatment of acute myeloid leukemias and myelodysplastic syndromes. While clinical responses are attributed to epigenetic effects and induction of apoptosis in malignant cells, these azanucleosides also affect antitumor immune responses. NK cells as components of innate immunity may confine development and progression of cancer. Numerous therapeutic strategies presently aim to reinforce NK reactivity against hematopoietic malignancies. We here comparatively analyzed the effect of the two clinically available azanucleosides and report that NK cytotoxicity and IFN‐γ production are significantly impaired by pharmacological concentrations of azacytidine but enhanced by decitabine. This was not due to alterations in the target cells but caused by direct effects on NK cells depending on the chemical modifications by which azanucleosides differ from their physiological analogues. Although azacytidine impaired mRNA synthesis and induced apoptosis in NK cells, decitabine did not per se alter NK cell viability or reactivity but enhanced responsiveness to activating stimuli by inducing transcription of genes involved in NK reactivity. Tantalizingly, these effects were independent of incorporation of the azanucleosides into DNA during cell division. While azacytidine impairs NK antitumor immunity, decitabine augments NK reactivity by yet unidentified mechanisms and may thus serve well in therapeutic strategies combining its effects on malignant cells with its ability to enhance NK functions.
G‐protein‐coupled receptor for short‐chain fatty acids suppresses colon cancer
Authors: Tang Yong , Chen Yakun , Jiang Hongmei , Robbins Gregory T. , Nie Daotai
Published: August 2010

GPR43 is a G‐protein‐coupled receptor for short‐chain fatty acids (SCFAs). Expression of GPR43 is detected in hematopoietic tissues and the large intestine. SCFAs are derived from bacterial fermentation and metabolism of undigested dietary fibers and have been recognized for their cancer prevention activities in the colon. The role of SCFAs, particularly butyrate, in colon cancer therapy has been extensively studied, and its tumor suppressive functions are believed to be due to their intracellular actions, notably inhibition of histone deacetylase. In our study, we show that SCFAs also exert their antitumor effects via receptor GPR43 and that GPR43 is frequently lost in colon cancer cells. Immunohistostaining revealed that GPR43 immunoreactivity was high in normal colon tissues (N = 31) but was markedly reduced or completely lost in most colorectal adenocarcinoma tissues (N = 70) and their corresponding lymph node metastatic adenocarcinomas (N = 38). RT‐PCR analysis detected the presence of full length GPR43 mRNA in only one (HT‐29) of nine established human colon cancer cell lines. Restoration of GPR43 expression in HCT8 human colonic adenocarcinoma cells induced G0/G1 cell cycle arrest and activated caspases, leading to increased apoptotic cell death after propionate/butyrate treatment. Restored GPR43 expression, coupled with propionate treatment, induced an upregulation of p21 and a decrease in the levels of cyclin D3 and cyclin‐dependent kinases (CDKs) 1 and 2, while the CDK4 and CDK6 levels remained unchanged. Our results suggest that GPR43 functions as a tumor suppressor by mediating SCFA‐induced cell proliferation inhibition and apoptotic cell death in colon cancer.
Safety and tolerability of a modified filter‐type device for leukocytapheresis using ACD‐A as anticoagulant in patients with mild to moderately active ulcerative colitis. Results of a pilot study
Authors: Muratov Vladislaw , Lundahl Joachim , Mandic‐Havelka Aleksandra , Elvin Kerstin , Öst Åke , Shizume Yasumasa , Furuya Kaoru , Löfberg Robert
Published: August 2010

Cellsorba™ is a medical device for leukocytapheresis (LCAP) treatment of ulcerative colitis (UC). Cellsorba™ EX Global type has been developed from Cellsorba E for intended use with ACD‐A as anticoagulant. We evaluated safety and efficacy of the modified Cellsorba using ACD‐A in a pilot trial comprising patients with active UC, despite receiving 5‐ASA. A total of 10 LCAP treatments/patients were administered. Safety assessment focused on clinical signs and symptoms, hematological variables, as well as levels of bradykinin and IL‐6. Efficacy was determined using the Mayo clinical/endoscopic scoring index as well histological assessment of biopsies. Additional aim was to evaluate the impact of apheresis system lines and filter on selected regulatory molecules. All six subjects completed the trial without any serious adverse events. WBC, platelet counts, and levels of bradykinin and IL‐6 were not significantly affected. The median Mayo score decreased from 8.0 to 3.5 at week 8 (and to 2 at week 16 for the responders). Four patients were responders, of whom two patients went into remission. Median histological scores decreased from 3.5 to 2.0 in these four patients. Concentration of LL‐37 increased within the apheresis system lines. LCAP with Cellsorba EX using ACD‐A as anticoagulant was found to be a safe and well‐tolerated procedure in patients with active UC. The positive impact on efficacy parameters merits further evaluation in a controlled fashion. J. Clin. Apheresis, 2010. © 2010 Wiley‐Liss, Inc.
Angiogenesis and Inflammation Signaling Are Targets of Beer Polyphenols on Vascular Cells
Authors: Negrão Rita , Costa Raquel , Duarte Delfim , Taveira Gomes Tiago , Mendanha Mário , Moura Liane , Vasques Luísa , Azevedo Isabel , Soares Raquel
Published: August 2010

Emerging evidence indicates that chronic inflammation and oxidative stress cluster together with angiogenic imbalance in a wide range of pathologies. In general, natural polyphenols present health‐protective properties, which are likely attributed to their effect on oxidative stress and inflammation. Hops used in beer production are a source of polyphenols such as xanthohumol (XN), and its metabolites isoxanthohumol (IXN) and phytoestrogen 8‐prenylnaringenin (8PN). Our study aimed to evaluate XN, IXN, and 8PN effects on angiogenesis and inflammation processes. Opposite in vitro effects were observed between 8PN, stimulating endothelial and smooth muscle cell (SMC) growth, motility, invasion and capillary‐like structures formation, and XN and IXN, which inhibited them. Mouse matrigel plug and rat skin wound‐healing assays confirmed that XN and IXN treatments reduced vessel number as well as serum macrophage enzymatic activity, whereas 8PN increased blood vessels formation in both assays and enzyme activity in the wound‐healing assay. A similar profile was found for serum inflammatory interleukin‐1β quantification, in the wound‐healing assay. Our data indicate that whereas 8PN stimulates angiogenesis, XN and IXN manifested anti‐angiogenic and anti‐inflammatory effects in identical conditions. These findings suggest that the effects observed for individual compounds on vascular wall cells must be carefully taken into account, as these polyphenols are metabolized after in vivo administration. The modulation of SMC proliferation and migration is also of special relevance, given the role of these cells in many pathological conditions. Furthermore, these results may provide clues for developing useful therapeutic agents against inflammation‐ and angiogenesis‐associated pathologies. J. Cell. Biochem. 111: 1270–1279, 2010. © 2010 Wiley‐Liss, Inc.
p53 and p21(Waf1) Are Recruited to Distinct PML‐Containing Nuclear Foci in Irradiated and Nutlin‐3a‐Treated U2OS Cells
Authors: Shen Hong , Maki Carl G.
Published: August 2010

Promyelocytic leukemia nuclear bodies (PML‐NBs) are multiprotein complexes that include PML protein and localize in nuclear foci. PML‐NBs are implicated in multiple stress responses, including apoptosis, DNA repair, and p53‐dependent growth inhibition. ALT‐associated PML bodies (APBs) are specialized PML‐NBs that include telomere‐repeat binding‐factor TRF1 and are exclusively in telomerase‐negative tumors where telomere length is maintained through alternative (ALT) recombination mechanisms. We compared cell‐cycle and p53 responses in ALT‐positive cancer cells (U2OS) exposed to ionizing radiation (IR) or the p53 stabilizer Nutlin‐3a. Both IR and Nutlin‐3a caused growth arrest and comparable induction of p53. However, p21, whose gene p53 activates, displayed biphasic induction following IR and monophasic induction following Nutlin‐3a. p53 was recruited to PML‐NBs 3–4 days after IR, approximately coincident with the secondary p21 increase. These p53/PML‐NBs marked sites of apparently unrepaired DNA double‐strand breaks (DSBs), identified by colocalization with phosphorylated histone H2AX. Both Nutlin‐3a and IR caused a large increase in APBs that was dependent on p53 and p21 expression. Moreover, p21, and to a lesser extent p53, was recruited to APBs in a fraction of Nutlin‐3a‐treated cells. These data indicate (1) p53 is recruited to PML‐NBs after IR that likely mark unrepaired DSBs, suggesting p53 may either be further activated at these sites and/or function in their repair; (2) p53–p21 pathway activation increases the percentage of APB‐positive cells, (3) p21 and p53 are recruited to ALT‐associated PML‐NBs after Nutlin‐3a treatment, suggesting that they may play a previously unrecognized role in telomere maintenance. J. Cell. Biochem. 111: 1280–1290, 2010. © 2010 Wiley‐Liss, Inc.
Regulation of borealin by phosphorylation at serine 219
Authors: Kaur Harpreet , Bekier Mike E. , Taylor William R.
Published: August 2010

The chromosomal passenger complex consisting of Borealin, INCENP, Survivin, and Aurora B follows a dynamic pattern of localization to perform its role as a regulator of chromosome alignment, aspects of the spindle assembly checkpoint, and cytokinesis. Post‐translational modifications of chromosomal passenger proteins play an important role in regulating the localization and function of the complex. Borealin displays a slower electrophoretic mobility during mitosis as a result of phosphorylation. Here we show that phosphorylation at S219 is responsible for this mobility shift. An S219A mutant of Borealin that cannot be phosphorylated at this site displays a defect in centromere localization that is evident in cells arrested in mitosis with nocodazole. Further, the S219A form of Borealin is unable to efficiently rescue mitotic defects that occur upon knock‐down of the endogenous protein. These defects are correlated with a reduction in the intensity of Mad2 staining at kinetochores in cells expressing the S219A form of Borealin. These results highlight an important role for phosphorylation of Borealin at S219 in the proper progression through mitosis. J. Cell. Biochem. 111: 1291–1298, 2010. © 2010 Wiley‐Liss, Inc.
FGF2 promotes Msx2 stimulated PC‐1 expression via Frs2/MAPK signaling
Authors: Li Yan , Liu Jin , Hudson Mark , Kim Sungsu , Hatch Nan E.
Published: August 2010

PC‐1 is an enzymatic generator of pyrophosphate and a critical regulator of tissue mineralization. We previously showed that fibroblast growth factor‐2 (FGF2) specifically induces PC‐1 expression in calvarial pre‐osteoblasts and that this occurs via a transcriptional mechanism involving Runx2. Because aberrant FGF signaling and Msx2 activity result in similar craniofacial skeletal defects and because Msx2 is an established regulator of osteoblastic gene expression, here we investigate Msx2 as an additional mediator of PC‐1 gene expression. mRNA analysis and experiments utilizing PC‐1 gene promoter/luciferase reporter constructs demonstrate that Msx2 promotes transcription of the PC‐1 gene downstream of FGF2. Results indicate that both Msx2 and Runx2 are recruited to a conserved core Msx2 binding site within the PC‐1 gene promoter upon FGF2 stimulation, and that Msx2 and Runx2 function together to induce PC‐1 gene expression in osteoblastic cells. Here we show that FGF signaling promotes Msx2 transcriptional activity on the PC‐1 gene promoter via the Frs2/MAPK signaling pathway. To our knowledge, this is the first report of Msx2 functioning as a transcriptional enhancer downstream of FGF2 in calvarial pre‐osteoblasts. As activating mutations in FGF receptors and Msx2 result in similar craniofacial skeletal disorders, our findings support the idea that FGF signaling and Msx2 activity influence cranial osteogenesis via the same molecular mechanism. J. Cell. Biochem. 111: 1346–1358, 2010. © 2010 Wiley‐Liss, Inc.
Artificial neural network‐based drug design for diabetes mellitus using flavonoids
Authors: Patra Jagdish C. , Chua Boon H.
Published: August 2010

Diabetes mellitus is a chronic metabolic disease involving the failure to regulate glucose blood levels in the body and has been linked with numerous detrimental complications. Studies have shown that these complications can be linked to the activities of aldose reductase (AR), an enzyme of the polyol pathway. Flavonoids have been identified as good AR inhibitors (ARIs) and are also strong antioxidants with radical scavenging (RS) activity. As such, flavonoids show potential to become a better class of ARIs because they are able to concurrently address the oxidative stress issue. In this article, we carried out quantitative structure‐activity relationship analysis of flavones and flavonols (members of flavonoid family) using artificial neural networks. Three computer experiments were conducted to study the influence of hydrogen (H), hydroxyl (OH), and methoxyl (CH3) functional groups on eight substitution sites of the lead flavone molecule and to predict potential ARIs. Of 6561 possible flavones and flavonols, in experiment 1, we predicted 69 potent ARIs, and in experiment 2, we predicted 346 compounds with strong RS activity. In experiment 3, we combined these results to find overlapping compounds with both strong AR inhibition and RS activity and we are able to predict 10 potent compounds with strong AR inhibition (IC50< 0.3 μM) and RS activity (IC25< 1.0 μM). These 10 compounds show promise of being good therapeutic agents in the prevention of diabetic complications and is suggested to undergo further wet bench experimentation to prove their potency. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011
Pro‐inflammatory angiogenesis is mediated by p38 MAP kinase
Authors: Rajashekhar Gangaraju , Kamocka Malgorzata , Marin Abby , Suckow Mark A. , Wolter William R. , Badve Sunil , Sanjeevaiah Aravind Raj , Pumiglia Kevin , Rosen Elliot , Clauss Matthias
Published: August 2010

Chronic inflammation is tightly linked to diseases associated with endothelial dysfunction including aberrant angiogenesis. To better understand the endothelial role in pro‐inflammatory angiogenesis, we analyzed signaling pathways in continuously activated endothelial cells, which were either chronically exposed to soluble TNF or the reactive oxygen species (ROS) generating H2O2, or express active transmembrane TNF. Testing in an in vitro capillary sprout formation assay, continuous endothelial activation increased angiogenesis dependent on activation of p38 MAP kinase, NADPH oxidase, and matrix metalloproteinases (MMP). p38 MAP kinase‐ and MMP‐9‐dependent angiogenesis in our assay system may be part of a positive feed forward autocrine loop because continuously activated endothelial cells displayed up‐regulated ROS production and subsequent endothelial TNF expression. The pro‐angiogenic role of the p38 MAP kinase in continuously activated endothelial cells was in stark contrast to the anti‐angiogenic activity of the p38 MAP kinase in unstimulated control endothelial cells. In vivo, using an experimental prostate tumor, pharmacological inhibition of p38 MAP kinase demonstrated a significant reduction in tumor growth and in vessel density, suggesting a pro‐angiogenic role of the p38 MAP kinase in pathological angiogenesis in vivo. In conclusion, our results suggest that continuous activation of endothelial cells can cause a switch of the p38 MAP kinase from anti‐angiogenic to pro‐angiogenic activities in conditions which link oxidative stress and autocrine TNF production. J. Cell. Physiol. 226: 800–808, 2011. © 2010 Wiley‐Liss, Inc.
Changes in blood flow velocity in the radial artery during 1‐hour ultrasound monitoring with a 2‐MHz transcranial probe—A pilot study
Authors: Bardoň Petr , Školoudík David , Langová Kateřina , Herzig Roman , Kaňovský Petr
Published: August 2010

Purpose

Multiple biologic effects of ultrasound on the human body have been described. Our aim was to monitor changes in blood flow velocities in the radial artery during continuous pulsed wave Doppler monitoring (DM).

Methods

Fifteen healthy volunteers (8 males; mean age 55 ± 17 years) underwent two 1‐hour sessions of left radial artery DM using a diagnostic transcranial 2‐MHz pulsed‐wave transducer. Blood flow velocities were recorded twice at 2‐minute intervals, for the measurement of peak systolic velocity, end‐diastolic velocity, and mean flow velocity, and the calculation of pulsatility index, and resistance index. Insonation was either intermittent (by periods <10 seconds) or continuous during the first session, and conversely during the second session 2 weeks later.

Results

Blood flow velocities and indices fluctuated during both sessions. These changes were symmetrical during the intermittent DM session. In contrast, end‐diastolic velocity increased while pulsatility index and resistance index decreased significantly during the continuous DM session (p < 0.05 for all three parameters). The changes in peak systolic velocity and mean flow velocity did not differ between sessions.

Conclusions

One‐hour sonographic Doppler monitoring using a 2‐MHz diagnostic transcranial PW Doppler probe may induce peripheral vasorelaxation in humans. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010
Sonographic assessment of fatty liver infiltration using the measurement of para‐ and perirenal fat thickness
Authors: Kawasaki Satsuki , Hasegawa Osamu , Satoh Shinobu , Numata Kazushi , Terauchi Yasuo
Published: August 2010

Purpose

Usefulness of abdominal ultrasonography for quantitative estimation of fatty liver by measurement of para‐ and perirenal sonographic fat thickness (UFT) was investigated.

Methods

Study subjects were 286 patients hospitalized for the treatment of diabetes. These subjects underwent blood chemistry studies, abdominal ultrasonography, and CT. On sonography, the thickness of combined para‐ and perirenal fat was measured between the kidney and the inner aspect of the abdominal musculature. Measurements on both sides were averaged as the UFT. Fatty liver infiltration was graded on a scale of grade 0 to 3: 0, none; 1, mild; 2, moderate; and 3, severe. With abdominal CT, the ratio of CT attenuation value of the liver to that of the spleen (L/S ratio) was measured.

Results

A positive correlation was found between UFT and FL grade or between UFT and L/S ratio (p< 0.0001). Positive correlations were also found between UFT and glutamic pyruvic transaminase (p< 0.05), or cholinesterase (p< 0.0001).

Conclusion

Measurement of UFT is a useful method for the quantification of fatty liver as well as for the quantification of visceral fat. © 2010 Wiley Periodicals, Inc. J Clin Ultrasound, 2010
Synthesis, characterization, and antimicrobial activity of 3′‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)spiro[indoline‐3,2′‐thiazolidine]‐2,4′‐diones
Authors: Mhaske Pravin C. , Shelke Shivaji H. , Jadhav Rahul P. , Raundal Hemant N. , Patil Sachin V. , Patil Amar A. , Bobade Vivek D.
Published: August 2010

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A series of 3′‐(4‐(2‐methyl/phenyl/benzylthiazol‐4‐yl)phenyl)spiro[indoline‐3,2′‐thiazolidine]‐2,4′‐diones was synthesized. The structures of the synthesized compounds were evaluated by analytical and spectral (IR, 1H NMR, 13C NMR, LC‐MS, and elemental analysis) methods. All the synthesized compounds were screened for qualitative (Zone of inhibition) and quantitative antimicrobial activities (MIC). Most of the derivatives showed good activity towards Gram‐positive and Gram‐negative bacteria. J. Heterocyclic Chem., (2010).
An efficient one‐pot solvent‐free synthesis of 2,3‐dihydroquinazoline‐4(1H)‐ones via Al/Al2O3 nanoparticles
Authors: Kassaee M. Z. , Rostamizadeh Shahnaz , Shadjou Nasrin , Motamedi Elahe , Esmaeelzadeh Maryam
Published: August 2010

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An efficient one‐pot, solvent‐free method is reported for the synthesis of 2‐phenyl‐2,3‐dihydroquinazoline‐4(1H)‐one as well as its o‐Cl, o‐OMe, m‐Br, m‐NO2, p‐OH, p‐NO2, p‐CN, p‐PhCH2O, p‐Cl, p‐F, p‐Br, p‐Me, and o,m‐dichloro derivatives, using our “as‐prepared” arc discharge fabricated Al/Al2O3 nanoparticles. Compared with our previous report and other known methods, this route gives higher yields with shorter reaction times, whereas its green catalyst appears recyclable at least four times‐with minor decrease in its catalytic activity, under mild conditions. J. Heterocyclic Chem., (2010).
Aberrant stress‐induced Hsp70 expression in immune cells in multiple sclerosis
Authors: Cwiklinska Hanna , Mycko Marcin P. , Szymanska Bozena , Matysiak Mariola , Selmaj Krzysztof W.
Published: August 2010

Heat shock protein 70 (Hsp70), a prominent member of the heat shock protein family, is a stress‐induced chaperone, contributing to the “protein triage” mechanism. However, we and others have previously shown that chaperonin activity of Hsp70 also promotes immune recognition of protein/peptide antigens, including myelin autoantigens. Hsp70 has been strikingly elevated in multiple sclerosis (MS) lesions. In a search for the mechanism of Hsp70 up‐regulation in MS, we analyzed Hsp70 expression in peripheral blood mononuclear cells (PBMCs) from MS patients (n = 49), healthy controls (n = 40), and patients with rheumatoid arthritis, (RA; n = 13). Hsp70 was detected by Western blot, and Hsp70 levels were quantified by ELISA. We found that Hsp70 was expressed at low levels in ex vivo PBMCs. However, after heat shock, Hsp70 was up‐regulated significantly more (up to sixfold) in MS patients compared with healthy controls. This significant overproduction of Hsp70 was also seen following another stress condition, LPS stimulation. Hsp70 is a product of several independent genes, and we found the HSPA1B gene product to be the major form responsible for Hsp70 protein overexpression in PBMCs. Hsp70 overexpression was preceded by increased nuclear presence of heat shock factor 1 (HSF1). HSF1 activation depends on phosphorylation, and we found that inhibition of the A group of protein kinase C isoenzymes significantly reduced inducible Hsp70 production. These results indicate that immune cells from MS patients are more prone to Hsp70 induction under stress conditions, suggesting a possible link between Hsp70 overexpression and development of autoimmunity. © 2010 Wiley‐Liss, Inc.
Localized alteration of microtubule polymerization in response to guidance cues
Authors: Kelly Terri‐Ann N. , Katagiri Yasuhiro , Vartanian Keri B. , Kumar Pramukta , Chen Inn‐Inn , Rosoff William J. , Urbach Jeffery S. , Geller Herbert M.
Published: August 2010

Inhibition of microtubule dynamic instability prevents growth cone turning in response to guidance cues, yet specific changes in microtubule polymerization as growth cones encounter boundaries have not been investigated. In this study, we examined the rate and direction of microtubule polymerization in response to soluble nerve growth factor (NGF) and immobilized chondroitin sulfate proteoglycans (CSPGs) by expressing enhanced GFP‐EB3 in rat pheochromocytoma (PC12) cells. GFP‐EB3 comets were monitored in live cells using time‐lapse epifluorescent microscopy. With an automated tracking system, the rate of microtubule polymerization was calculated as the frame‐to‐frame displacement of EB3 comets. Our results demonstrate that the rate of microtubule polymerization is increased following NGF treatment, whereas contact with CSPGs decreases microtubule polymerization rates. This reduction in microtubule polymerization rates was specifically localized to neurites in direct contact with CSPGs and not at noncontacting neurites. Additionally, we found an increase in the percentage of microtubules polymerizing in the retrograde direction in neurites at CSPG boundaries, with a concomitant decrease in the rate of retrograde microtubule polymerization. These results implicate localized changes in microtubule dynamics as an important component of the growth cone response to guidance cues. © 2010 Wiley‐Liss, Inc.
Reduction of hippocampal N‐acetyl aspartate level in aged APPSwe/PS1dE9 transgenic mice is associated with degeneration of CA3 pyramidal neurons
Authors: Xu Wei , Zhan Yanqiang , Huang Wei , Wang Xuxia , Zhang Sumin , Lei Hao
Published: August 2010

Age‐related metabolic changes in the hippocampus of APPSwe/PS1dE9 mice were measured with long echo‐time in vivo 1H‐magnetic resonance spectroscopy (1H‐MRS). Thioflavine S staining and Nissl staining were used to characterize deposition of Aβ aggregates and neuronal degeneration in the transgenic animals, respectively. The results showed that the APPSwe/PS1dE9 mice had significantly decreased hippocampal N‐acetyl aspartate (NAA)/total creatine (tCr) level at 16 months of age, which was associated with degeneration of and intracellular deposition of thioflavine S‐positive materials in hippocampal CA3 pyramidal neurons. The results of this study provide direct evidence showing association among Aβ pathology (intracellular deposition of thioflavine S‐positive materials), neuronal degeneration, and metabolic changes observable with in vivo 1H‐MRS in the hippocampus of APPSwe/PS1dE9 mice. © 2010 Wiley‐Liss, Inc.
Molecular characterization of uropathogenic and diarrheagenic Escherichia coli pathotypes
Authors: Regua‐Mangia Adriana Hamond , Irino Kinue , da Silva Pacheco Raquel , Pimentel Bezerra Rose Mary , Santos Périssé André Reynaldo , Teixeira Lucia Martins
Published: August 2010

In this study diarrheagenic and uropathogenic Escherichia coli (UPEC) strains were comparatively characterized according to serotype, hemolytic activity, protein polymorphism among housekeeping enzymes, phylogenetic group and urovirulence genes. Intra‐serogroup/serotype variations were observed. Hemolytic activity was detected in 100%, 93%, 67% and 39% of UPEC, EAEC, EPEC and ETEC strains, respectively. The alpha‐hemolytic phenotype was observed in all pathogenic groups while beta‐hemolytic phenotype was less frequent. PCR phylotyping revealed higher prevalence of diarrheagenic E. coli in groups A and D while uropathogenic strains were mainly found in subgroup B2. Amplification assays revealed that 74%, 45% and 22% of UPEC, EAEC and EPEC strains, respectively, carried at least one of the urovirulence sequences. The molecular typing system revealed a pathotype‐specific clonal group distribution and showed a closer relationship between the EAEC and UPEC. Additionally, the occurrence of urovirulence traits, especially those related to iron acquisition, was more frequent among EAEC and UPEC than among the other E. coli pathotypes. This observation is of special value considering that the EAEC pathotype constitutes an emerging group of enteropathogens, particularly, in developing countries, and information on their pathogenic and phylogenetic characteristics is still scarce. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Water‐soluble red pigments from Isaria farinosa and structural characterization of the main colored component
Authors: Velmurugan Palanivel , Lee Yong Hoon , Nanthakumar Kuppanan , Kamala‐Kannan Seralathan , Dufossé Laurent , Mapari Sameer AS , Oh Byung‐Taek
Published: August 2010

The present study describes the red pigment synthesized by the filamentous fungi Isaria farinosa under submerged culture conditions. The pigment production was optimal under the following conditions: pH 5, agitation speed 150 rpm, temperature 27 °C, incubation time 192 h, light source total darkness, sucrose and glucose as carbon source, yeast extract, meat peptone and monosodium glutamate at a fixed concentration of 3% as nitrogen source. The addition of 10 mM CaCl2 to the culture medium increased the biomass and pigment production. Structural elucidation of the pigment using gas chromatography‐mass spectrometry, Fourier transform infrared spectroscopy and 1H nuclear magnetic resonance spectroscopy revealed that the red pigment contains an anthraquinone‐related compound. In addition, the isolated pigment was water soluble, and was stable when exposed to salt solution (96.1% of stability after treatment with sodium chloride), acid (72.1% with citric acid), heat (86.2% at 60 °C), and sunlight (99.4%). These results are promising to further exploit the fungal culture of Isaria farinosa for producing the red pigment and, subsequently, to considerably increase its yield. The study has commercial importance in the production of Isaria farinosa pigment for industrial application after considerable toxicological examination. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Vancomycin‐resistant enterococci from Portuguese wastewater treatment plants
Authors: Araújo Carlos , Torres Carmen , Silva Nuno , Carneiro Catarina , Gonçalves Alexandre , Radhouani Hajer , Correia Susana , da Costa Paulo Martins , Paccheco Rui , Zarazaga Myriam , Ruiz‐Larrea Fernanda , Poeta Patrícia , Igrejas Gilberto
Published: August 2010

The objective of this study was to evaluate the incidence of vancomycin resistant enterococci in sludge and sewage of urban and poultry‐slaughterhouse wastewater treatment plants. A total of 17 vancomycin resistant enterococci (eight vanA ‐containing Enterococcus faecium and nine vanC1/vanC2 ‐containing Enterococcus gallinarum/casseliflavus) were found among 499 isolates of sewage and sludge samples of 14 urban and nine poultry‐slaughterhouse wastewater treatment plants. These seventeen VRE isolates showed resistance to kanamycin (n = 8), tetracycline (n = 7), erythromycin (n = 7), ciprofloxacin (n = 7), ampicillin (n = 7), streptomycin (n = 6), and gentamicin (n = 2). The tetM gene, related with tetracycline resistance, was found in six of eight van A‐containing isolates, in all seven vanC‐1 isolates and in one of two vanC‐2 isolates. The ermB gene in seven erythromycin‐resistant isolates; and the aac6 ′‐aph2 ″ gene in the two high‐level‐gentamicin‐resistant isolates. Moreover, two vanA ‐containing E. faecium isolates harbored the hyl virulence gene, and three isolates the entA bacteriocin gene. The purK‐1 allele was detected in our urban vanA ‐containing E. faecium isolate, and we found as well the purK‐6 allele in one poultry‐slaughterhouse vanA ‐containing E. faecium isolate. This study suggests that the wastewater treatment plants might be an important source of dissemination of antibiotic‐resistant enterococci in Portugal. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Mutual influence of soil basidiomycetes and white mustard plants on their enzymatic and catabolic activities
Authors: Gramss Gerhard , Mascher René
Published: August 2010

Liquid and volatile emanations in interactions of soil basidiomycetes with herbs affect fungal oxidoreductases and stress‐related plant peroxidases (PO). In this study, gnotobiotic co‐cultures between 6 non‐pathogenic saprobes and 2 ectomycorrhizal basidiomycetes with the non‐host plant white mustard were established on glucose‐salt medium with the respective controls. Determined were oxidoreductase activities for culture fluids and plant tissues at initial fungal idiophase and degradation rates of Remazol‐BBR and 5 PAHs. In culture fluids of Agaricus arvensis, A. porphyrizon, Lepista nebularis, Stropharia rugoso‐annulata, and Hypholoma fasciculare (group‐5), the laccase‐deficient plant enabled activity increases in fungal laccase (by 2300‐fold), in extracellular (fungal and?) plant‐derived peroxidases (by 21‐fold), and in the dissipation of phenanthrene and anthracene. Oxidative activities in roots rose by 46000‐fold during adsorption of fungal laccases. Increases in the stress‐related shoot‐PO (by 4.1‐fold) were exclusively elicited by group‐5 saprobes and correlated with plant‐phenolic‐mediated formations of Mn(III) and increases in Remazol BBR bleaching. Agaricus bisporus and the ectomycorrhizal Hebeloma crustuliniforme and Suillus granulatus did not respond to plant emanations with elevated laccase activities but solubilized apparently root‐surface PO. They failed to elicit stress‐related activity increases of PO in white mustard shoot and prevented Mn(III) formation in several tissues. It is concluded that white mustard emanations promoted the catabolic performance of the plant‐stress eliciting group‐5 saprobes but not of A. bisporus and the ectomycorrhizal fungi with their low stress‐inducing potential. The nature of the plant‐released stimuli and the classes of fungus‐released stress agents discussed must be determined in further studies. (© 2011 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)
Biomechanical properties of mixtures of blood and synovial fluid
Authors: McCarty William J. , Luan Anna , Siddiqui Meena , Hansen Bradley C. , Masuda Koichi , Sah Robert L.
Published: August 2010

Synovial fluid (SF) is a viscous ultrafiltrate of plasma that lubricates articulating joint motion. During acute trauma and certain cartilage repair procedures, blood is introduced into the joint and mixes with variable amounts of SF. The hypothesis of this study was that the dilution of blood with SF alters the rheological properties of the blood and the mechanical properties of the clot formed. The objectives were to determine the composition (solid fraction, protein content), coagulation (fibrin polymerization time, torsional strength), and mechanical (stiffness, permeability) properties of mixtures of blood with 10% or 50%SF. While the initial stages of coagulation of blood were not markedly affected by the presence of the SF, dilution with SF altered the coagulation torque profile over time, decreased the final clot structure mechanical stiffness (42–90% decrease), and increased the fluid permeability of the clots (41‐ to 468‐fold). Compared to diluting blood with PBS, SF had a smaller effect on the mechanical properties of the clot, possibly due to the presence of high molecular weight hyaluronan. These properties of blood/SF mixtures may facilitate an understanding of the repair environment in the joint and of mechanisms of cartilage repair. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:240–246, 2011
Raman microspectroscopic evidence that dry‐fixing preserves the temporal pattern of non‐specific differentiation in live human embryonic stem cells
Authors: Konorov Stanislav O. , Schulze H. Georg , Caron Nicolas J. , Piret James M. , Blades Michael W. , Turner Robin F. B.
Published: August 2010

Raman microspectroscopy allows the classification of populations of human embryonic stem cells (hESCs) in different stages of differentiation based on the relative intensities of certain amino acid and nucleic acid bands. Here, we report the results of a comparative study of the Raman spectra of live cells versus cells killed and fixed by rapid desiccation, focusing on the ratio of intensities at 757 cm−1 (tryptophan) and 784 cm−1 (DNA and RNA). We observe that the same temporal pattern emerges over a 3‐week time course in both sample types. This suggests that prolonged observations of dry‐fixed cells can yield high signal‐to‐noise chemical images that cannot be obtained from colonies of living cells where the time scale of significant biological changes are comparable to the time scale of the measurement. This permits, for example, comparison of the spatial distributions of cells at different stages of differentiation within the same colonies. Copyright © 2010 John Wiley & Sons, Ltd.
Transition of chromium oxyhydroxide nanomaterials to chromium oxide: a hot‐stage Raman spectroscopic study
Authors: Yang Jing (Jeanne) , Martens Wayde N. , Frost Ray L.
Published: August 2010

The transition of disc‐like chromium hydroxide nanomaterials to chromium oxide nanomaterials has been studied by hot‐stage Raman spectroscopy. The structure and morphology of α‐CrO(OH) synthesised using hydrothermal treatment were confirmed by X‐ray diffraction (XRD) and transmission electron microscopy (TEM). The Raman spectrum of α‐CrO(OH) is characterised by two intense bands at 823 and 630 cm−1 attributed to ν1 CrIIIO symmetric stretching mode and the band at 1179 cm−1 attributed to CrIIIOH δ deformation modes. No bands are observed above 3000 cm−1. The absence of characteristic OH stretching vibrations may be due to short hydrogen bonds in the α‐CrO(OH) structure. Upon thermal treatment of α‐CrO(OH), new Raman bands are observed at 599, 542, 513, 396, 344 and 304 cm−1, which are attributed to Cr2O3. This hot‐stage Raman study shows that the transition of α‐CrO(OH) to Cr2O3 occurs before 350 °C. Copyright © 2010 John Wiley & Sons, Ltd.
Temperature effects on a doubly tethered diproline chiral stationary phase: Hold‐up volume, enantioselectivity and robustness
Authors: Lao Wenjian , Gan Jay
Published: August 2010

Effect of temperature on hold‐up volume, enantioselectivity and robustness of a novel doubly tethered diproline chiral stationary phase (CSP1) was studied. In‐column end‐capping of residual silanol was utilized as a tool to exhibit in situ change of CSP1. The hold‐up volume marker, 1,3,5‐tri‐tert‐butylbenzene, was observed to be weakly retained (<1 s ) on a 5 cm×4.6 mm chiral column, and its retention time was changed with the carrier solvent and column temperature. The apparent thermodynamic parameters of 1,3,5‐tri‐tert‐butylbenzene indicated an enthalpy‐driven retention process with the hexane/isopropanol mobile phase, while an entropy‐driven process with the hexane/methyl tert‐butyl ether mobile phase. The ΔΔH and ΔΔS values of chiral separation for the four probes including 1,1′‐bi‐2‐naphthol and warfarin were negative on CSP1. Nonlinear van't Hoff plots were observed for some analytes before and after the end‐capping treatment. Depending on compound, end‐capping strengthened or weakened the enantioseparation. Moreover, the enantioselectivity of CSP1 was shown to be robust by testing with heating–cooling cycles and step‐temperature programs.
Poly(N‐vinylimidazole)‐grafted capillary for electrophoresis prepared by surface‐initiated atom transfer radical polymerization
Authors: Li Jing , Han Haifeng , Wang Qing , Liu Xia , Jiang Shengxiang
Published: August 2010

A CE method for poly(N‐vinylimidazole) (PVI)‐grafted capillaries by the surface‐initiated atom transfer radical polymerization has been developed. The coating was prepared with N‐vinylimidazole as the monomer, 2‐bromo‐2‐methyl‐N‐[3‐(triethoxysilyl) propyl] propanamide (BTPAm) as the initiator and CuCl/CuCl2/2,2′‐bipyridine as the catalyst and ligand. The direction and magnitude of EOF in the PVI‐grafted capillary were investigated in a pH range of 3.0–9.0. The results indicated that the EOF could be modulated by varying the pH value of the buffer and an anodic EOF was obtained at pH values below 6.5. A significant improvement in reproducibility and reduction of EOF appeared on the PVI‐grafted capillary when compared with the uncoated capillary. Furthermore, the polymer coated capillaries were applied to the separations of the inorganic anions, organic acids and basic proteins and baseline separations were achieved with short analysis time and high reproducibility.
Physical characterization and evaluation of HPLC columns packed with superficially porous particles
Authors: Baker Jared S. , Vinci John C. , Moore Amber D. , Colón Luis A.
Published: August 2010

Two HPLC columns packed with superficially porous packing material (Kinetex™ 1.7 and 2.6 μm C18 particles) were evaluated in terms of their physical properties and performance characteristics. These columns were compared to a column packed with a sub‐2 μm totally porous material and to a HaloTM column packed with 2.7 μm C18 superficially porous packing. The columns packed with superficially porous particles displayed a comparably narrower size distribution, which is narrower than the distribution of the totally porous sub‐2 μm particles. Physical characteristics of the Kinetex™ particles were evaluated in terms of surface area, pore diameter, and specific pore volume. Total, external, internal, and shell porosities among the four different columns were evaluated and compared. The specific permeability for the Kinetex™ columns showed values close to those predicted by the Kozeny–Carman equation. All four columns were evaluated in terms of their chromatographic performance and compared using the Knox equation. The columns packed with the 2.6 and 2.7 μm superficially porous materials showed reduced plate heights below 2, whereas the sub‐2 μm particles showed values of 2.2 and above.
Middle turbinectomy for exposure in endoscopic endonasal transsphenoidal surgery: When is it necessary?
Authors: Guthikonda Bharat , Nourbakhsh Ali , Notarianni Christina , Vannemreddy Prasad , Nanda Anil
Published: August 2010

Objectives:

To evaluate the benefits of middle turbinectomy on the exposure of the skull base structures.

Design:

An anatomical study on 20 fresh cadaver heads.

Methods:

The extent of the exposure of the skull base structures during endoscopic endonasal approach has not been addressed specifically in respect to the whether or not the middle turbinectomy is performed. We compared the extent of exposure obtained by endonasal transsphenoidal approaches without middle turbinectomy (NMT), with unilateral turbinectomy (UMT), and with bilateral turbinectomy (BMT). Our preselected target points in the skull base consisted of sella turcica, tuberculum sella, planum sphenoidale, clivus (upper and middle third), and ipsilateral sphenopalatine artery (SPA).

Results:

Of our preselected anatomic target points, only the middle third of the clivus and ipsilateral SPA had enhanced exposure in UMT (100% for both structures) compared to NMT (45% and 20%, respectively). The addition of a BMT did not provide added exposure to any target compared with a UMT.

Conclusions:

Middle turbinectomy may not be necessary for endonasal transsphenoidal approach to the lesions of the sella, planum sphenoidale, and upper third of the clivus. However, gaining access to the middle clival region is facilitated by resection of middle turbinate. Laryngoscope, 2010
Expression of mucin (MUC) genes in mucoepidermoid carcinoma
Authors: Shemirani Nima , Osipov Vladimir , Kolker Alex , Khampang Pawjai , Kerschner Joseph E.
Published: August 2010

Objectives/Hypothesis:

Mucoepidermoid carcinoma (MEC) is the most common malignant salivary gland tumor. The presence of mucin (MUC) genes has been correlated with patient prognosis using immunohistochemical techniques. This study was undertaken to 1) investigate the expression of newly discovered MUC genes in MEC specimens, 2) assess the correlation of this expression to prognosis, and 3) further investigate the correlation of previously identified MUC genes to prognosis using molecular techniques.

Study Design:

Retrospective chart review and sample isolation.

Methods:

Twenty‐three patients with a diagnosis of MEC underwent mucin gene analysis of tumor and normal surrounding salivary gland tissue. Initial expression analysis of recently identified mucin genes MUC 12, 13, 17, 18, and 19 was performed using reverse transcription‐polymerase chain reaction (RT‐PCR) followed by quantitative assessment with quantitative PCR. Additional assessments of mucin genes MUC 1 and MUC 4, which have previously been associated with MEC, were also analyzed with real‐time RT‐PCR.

Results:

MEC was associated with MUC 19 expression in 65% of tumor samples compared to only 26% of normal tissue (P = .02). MUC 18 demonstrated equal expression in both tumor and normal tissue. MUC 12 and 17 were not expressed in either MEC or normal salivary gland. MUC 13 was found in 13% of tumors and 0% of normal samples. MUC 1 and MUC 4 were expressed 4.2‐ and 21‐fold higher in stage I disease in tumor tissue compared to normal, respectively.

Conclusions:

Presence of MUC 19 is suggestive of mucoepidermoid carcinoma, and higher expression of MUC 1 and MUC 4 is correlated with earlier stage disease. Laryngoscope, 2011