bluuebunny/crossref_metadata_2025_split huggingface dataset:
Human recombinant interleukin‐4 inhibits lymphokine‐activated killer activity of sheep erythrocyte rosette‐forming (E+) and ‐non‐forming (E−) human lymphocytes
Authors: Gerosa Franca , Tommasi Marina , Gerosa Massimo , Tridente Giuseppe 
Published: April 2012

AbstractThe effect of human recombinant interleukin‐4 (rIL‐4) on lymphokine‐activated killer activity (LAK) of peripheral blood lymphocytes (PBL) as well as sheep erythrocyte rosette‐forming (E+) and ‐non‐forming (E–) lymphocytes stimulated by human recombinant interleukin‐2 (rIL‐2) has been investigated. rIL‐4 drastically inhibited LAK activity of PBL cultured for 18 hr and for 5 days in the presence of rIL‐2. Distribution of T, B and IgG Fc‐receptor‐bearing lymphocytes, as assessed by immunofluorescence and flow cytometry, was no different at the end of the culture in the presence of rIL‐2 plus rIL‐4 than with rIL‐2 alone. LAK activity of E+ and E– lymphocytes was similarly inhibited. Finally, rIL‐4 did not affect the natural killer (NK) activity of rIL‐2‐activated PBL as assessed by the capacity of these cells to kill the appropriate NK target.
Nalidixic acid and oxolinic acid reversibly suppress 3‐methylcholanthrene‐induced cell transformation of BALB/3T3 mouse cells
Authors: Kaneko Motohisa , Horikoshi Junko 
Published: April 2012

AbstractThe effects of nalidixic acid (Nal) and oxolinic acid (Oxl), synthetic antibacterial compounds that inhibit bacterial DNA gyrase, on 3‐methylcholanthrene (MC)‐induced transformation of BALB/3T3 mouse cells were investigated. Exposure of the cells to Nal or Oxl for 2 weeks at any time during 4 weeks of incubation following MC treatment suppressed MC‐induced transformation. Nal and Oxl also suppressed the enhancement of transformation by 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA) initiated by MC. The suppression of transformation by Nal was released by exposure of the cells to TPA after removal of Nal. Since the suppressive effects of Nal and Oxl on transformation were time‐related, they may be due to epigenetic changes.
Experimental model of biofilm implant‐related osteomyelitis to test combination biomaterials using biofilms as initial inocula
Authors: Williams Dustin L. , Haymond Bryan S. , Woodbury Kassie L. , Beck J. Peter , Moore David E. , Epperson R. Tyler , Bloebaum Roy D. 
Published: April 2012

AbstractCurrently, the majority of animal models that are used to study biofilm‐related infections use planktonic bacterial cells as initial inocula to produce positive signals of infection in biomaterials studies. However, the use of planktonic cells has potentially led to inconsistent results in infection outcomes. In this study, well‐established biofilms of methicillin‐resistant Staphylococcus aureus were grown and used as initial inocula in an animal model of a Type IIIB open fracture. The goal of the work was to establish, for the first time, a repeatable model of biofilm implant‐related osteomyelitis, wherein biofilms were used as initial inocula to test combination biomaterials. Results showed that 100% of animals that were treated with biofilms developed osteomyelitis, whereas 0% of animals not treated with biofilm developed infection. The development of this experimental model may lead to an important shift in biofilm and biomaterials research by showing that when biofilms are used as initial inocula, they may provide additional insights into how biofilm‐related infections in the clinic develop and how they can be treated with combination biomaterials to eradicate and/or prevent biofilm formation. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A 2012.
Functional biomaterials for cartilage regeneration
Authors: Ge Zigang , Li Chao , Heng Boon Chin , Cao Guoxin , Yang Zheng 
Published: April 2012

AbstractThe injury and degeneration of articular cartilage and associated arthritis are leading causes of disability worldwide. Cartilage tissue engineering as a treatment modality for cartilage defects has been investigated for over 20 years. Various scaffold materials have been developed for this purpose, but has yet to achieve feasibility and effectiveness for widespread clinical use. Currently, the regeneration of articular cartilage remains a formidable challenge, due to the complex physiology of cartilage tissue and its poor healing capacity. Although intensive research has been focused on the developmental biology and regeneration of cartilage tissue and a diverse plethora of biomaterials have been developed for this purpose, cartilage regeneration is still suboptimal, such as lacking a layered structure, mechanical mismatch with native cartilage and inadequate integration between native tissue and implanted scaffold. The ideal scaffold material should have versatile properties that actively contribute to cartilage regeneration. Functional scaffold materials may overcome the various challenges faced in cartilage tissue engineering by providing essential biological, mechanical, and physical/chemical signaling cues through innovative design. This review thus focuses on the complex structure of native articular cartilage, the critical properties of scaffolds required for cartilage regeneration, present strategies for scaffold design, and future directions for cartilage regeneration with functional scaffold materials. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2526–2536, 2012.
Self‐supporting nanoporous alumina membranes as substrates for hepatic cell cultures
Authors: Hoess Andreas , Thormann Annika , Friedmann Andrea , Heilmann Andreas 
Published: April 2012

AbstractMembranes made from nanoporous alumina exhibit interesting properties for their use in biomedical research. They show high porosity and the pore diameters can be easily adjusted in a reproducible manner. Nanoporous alumina membranes are thus ideal substrates for the cultivation of polar cells (e.g., hepatocytes) or the establishment of indirect co‐cultures. The porous nature of the material allows supply of nutrients to both sides of adherent cells and the exchange of molecules across the membrane. However, it is well‐known that surface features in the nanometer range affect cellular behavior. In this study, the response of HepG2 cells to nanoporous alumina membranes with three different pore diameters, ranging from 50 to 250 nm, has been evaluated. The cellular interactions with the nanoporous materials were assessed by investigating cell adhesion, morphology, and proliferation. Cell functionality was measured by means of albumin production. The membranes supported good cell adhesion and spreading. Compared to tissue culture plastic, the cells on the porous substrates developed distinct focal adhesion sites and actin stress fibers. Additionally, electron microscopical investigations revealed the penetration of cellular extensions into pores with diameters bigger than 200 nm. Furthermore, cell proliferation significantly increased with an increase in pore diameter, whereas the albumin production followed a reverse trend. Thus, it seems to be possible to direct cellular behavior of HepG2 cells growing on nanoporous alumina by changing the pore diameter of the material. Hence, nanoporous alumina membranes can be useful culture substrates to develop new approaches in the field of liver tissue engineering. © 2012 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 100A: 2230–2238, 2012.
Effect of alendronate for reducing fracture by FRAX score and femoral neck bone mineral density: The fracture intervention trial
Authors: Donaldson Meghan G , Palermo Lisa , Ensrud Kristine E , Hochberg Marc C , Schousboe John T , Cummings Steven R 
Published: April 2012

Abstract
The WHO Fracture Risk Assessment Tool (FRAX; http://www.shef.ac.uk/FRAX) estimates the 10-year probability of major osteoporotic fracture. Clodronate and bazedoxifene reduced nonvertebral and clinical fracture more effectively on a relative scale in women with higher FRAX scores. We used data from the Fracture Intervention Trial (FIT) to evaluate the interaction between FRAX score and treatment with alendronate. We combined the Clinical Fracture (CF) arm and Vertebral Fracture (VF) arm of FIT. The CF and VF arm of FIT randomized 4432 and 2027 women, respectively, to placebo or alendronate for 4 and 3 years, respectively. FRAX risk factors were assessed at baseline. FRAX scores were calculated by WHO. We used Poisson regression models to assess the interaction between alendronate and FRAX score on the risk of nonvertebral, clinical, major osteoporotic, and radiographic vertebral fractures. Overall, alendronate significantly reduced the risk of nonvertebral fracture (incidence rate ratio [IRR] 0.86; 95% confidence interval [CI], 0.75–0.99), but the effect was greater for femoral neck (FN) bone mineral density (BMD) T-score ≤ −2.5 (IRR 0.76; 95% CI, 0.62–0.93) than for FN T-score &gt; −2.5 (IRR 0.96; 95% CI, 0.80–1.16) (p = 0.02, interaction between alendronate and FN BMD). However, there was no evidence of an interaction between alendronate and FRAX score with FN BMD for risk of nonvertebral fracture (interaction p = 0.61). The absolute benefit of alendronate was greatest among women with highest FRAX scores. Results were similar for clinical fractures, major osteoporotic fractures, and radiographic vertebral fractures and whether or not FRAX scores included FN BMD. Among this cohort of women with low bone mass there was no significant interaction between FRAX score and alendronate for nonvertebral, clinical or major osteoporotic fractures, or radiographic vertebral fractures. These results suggest that the effect of alendronate on a relative scale does not vary by FRAX score. A randomized controlled trial testing the effect of antifracture agents among women with high FRAX score but without osteoporosis is warranted. © 2012 American Society for Bone and Mineral Research.
Aggregatibacter actinomycetemcomitans lipopolysaccharide regulates bone sialoprotein gene transcription
Authors: Li Xinyue , Zhou Liming , Takai Hideki , Sasaki Yoko , Mezawa Masaru , Li Zhengyang , Wang Zhitao , Yang Li , Wang Shuang , Matsumura Hiroyoshi , Kaneko Takashi , Yoshimura Atsutoshi , Ogata Yorimasa 
Published: April 2012

AbstractAggregatibacter actinomycetemcomitans (A. actinomycetemcomitans) is believed to be associated with aggressive periodontitis characterized by a rapid bone loss. A. actinomycetemcomitans lipopolysaccharide (LPS) has a similar structure to Escherichia coli LPS, and they are Toll‐like receptor 4 agonists. Bone sialoprotein (BSP) is an early marker of osteoblast differentiation. To investigate the effects of A. actinomycetemcomitans LPS on bone formation, we targeted BSP as a marker for osteogenic differentiation and bone formation. BSP mRNA levels were decreased by 0.1 µg/ml and increased by 0.01 µg/ml A. actinomycetemcomitans LPS at 6 h in osteoblast‐like ROS17/2.8 cells. In transient transfection analyses, 0.1 µg/ml decreased and 0.01 µg/ml A. actinomycetemcomitans LPS increased luciferase activities of the construct (−116 to +60). Introduction of 2 bp mutations to the constructs showed that the effects of A. actinomycetemcomitans LPS were mediated by a cAMP response element (CRE), a FGF2 response element (FRE), and a homeodomain protein‐binding site (HOX). Tyrosine kinase, ERK1/2, and PI3‐kinase/Akt participated in the effects of both 0.1 and 0.01 µg/ml A. actinomycetemcomitans LPS. The results of gel shift showed that 0.1 µg/ml decreased while 0.01 µg/ml A. actinomycetemcomitans LPS increased CRE‐, FRE‐, and HOX‐binding protein complexes formation at 6 h, and revealed that 0.01 µg/ml A. actinomycetemcomitans LPS induced BSP transcription through CREB1, JunD, Fra2, c‐Fos, Runx2, Dlx5, and Smad1 targeting those response elements. These studies therefore indicated that 0.1 µg/ml suppressed and 0.01 µg/ml A. actinomycetemcomitans LPS increased BSP gene transcription mediated through CRE, FRE, and HOX elements in the rat BSP gene promoter. J. Cell. Biochem. 113: 2822–2834, 2012. © 2012 Wiley Periodicals, Inc.
Sulfuretin from heartwood of Rhus verniciflua triggers apoptosis through activation of Fas, Caspase‐8, and the mitochondrial death pathway in HL‐60 human leukemia cells
Authors: Lee Kyung‐Won , Chung Kyung‐Sook , Seo Ji‐Hyung , Yim Sung‐Vin , Park Hee‐Jun , Choi Jung‐Hye , Lee Kyung‐Tae 
Published: April 2012

AbstractSulfuretin, a flavonoid isolated from heartwood of Rhus verniciflua, has been reported to have anti‐cancer activities but the underlying molecular mechanism was not clear. In this study, sulfuretin induced apoptosis by activating caspases‐8, ‐9, and ‐3 as well as cleavage of poly(ADP‐ribose) polymerase. Furthermore, treatment with sulfuretin caused mitochondrial dysfunctions, including the loss of mitochondrial membrane potential (ΔΨm), the release of cytochrome c to the cytosol, and the translocations of Bax and tBid. Sulfuretin also activated the extrinsic apoptosis pathway, that is, it increased the expressions of Fas and FasL, the activation of caspase‐8, and the cleavage of Bid. Furthermore, blocking the FasL–Fas interaction with NOK‐1 monoclonal antibody prevented the sulfuretin‐induced apoptosis. The therapeutical effect of sulfuretin in leukemia is due to its potent apoptotic activity through the extrinsic pathway driven by a Fas‐mediated caspase‐8‐dependent pathway. J. Cell. Biochem. 113: 2835–2844, 2012. © 2012 Wiley Periodicals, Inc.
In‐vivo patellar tendon kinematics during weight‐bearing deep knee flexion
Authors: Kobayashi Koichi , Sakamoto Makoto , Hosseini Ali , Rubash Harry E. , Li Guoan 
Published: April 2012

AbstractThis study quantified in‐vivo 3D patellar tendon kinematics during weight‐bearing deep knee bend beyond 150°. Each knee was MRI scanned to create 3D bony models of the patella, tibia, femur, and the attachment sites of the patellar tendon on the distal patella and the tibial tubercle. Each attachment site was divided into lateral, central, and medial thirds. The subjects were then imaged using a dual fluoroscopic image system while performing a deep knee bend. The knee positions were determined using the bony models and the fluoroscopic images. The patellar tendon kinematics was analyzed using the relative positions of its patellar and tibial attachment sites. The relative elongations of all three portions of the patellar tendon increased similarly up to 60°. Beyond 60°, the relative elongation of the medial portion of the patellar tendon decreased as the knee flexed from 60° to 150° while those of the lateral and central portions showed continuous increases from 120° to 150°. At 150°, the relative elongation of the medial portion was significantly lower than that of the central portion. In four of seven knees, the patellar tendon impinged on the tibial bony surface at 120° and 150° of knee flexion. These data may provide useful insight into the intrinsic patellar tendon biomechanics during a weight‐bearing deep knee bend and could provide biomechanical guidelines for future development of total knee arthroplasties that are intended to restore normal knee function. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1596–1603, 2012
Associated computational plasticity schemes for nonassociated frictional materials
Authors: Krabbenhoft K. , Karim M. R. , Lyamin A. V. , Sloan S. W. 
Published: April 2012

SUMMARYA new methodology for computational plasticity of nonassociated frictional materials is presented. The new approach is inspired by the micromechanical origins of friction and results in a set of governing equations similar to those of standard associated plasticity. As such, procedures previously developed for associated plasticity are applicable with minor modification. This is illustrated by adaptation of the standard implicit scheme. Moreover, the governing equations can be cast in terms of a variational principle, which after discretization is solved by means of a newly developed second‐order cone programming algorithm. The effects of nonassociativity are discussed with reference to localization of deformations and illustrated by means of a comprehensive set of examples. Copyright © 2012 John Wiley & Sons, Ltd.
Toxicity of hyperthermic intraperitoneal chemotherapy (HIPEC) in pediatric patients with sarcomatosis/carcinomatosis: Early experience and phase 1 results
Authors: Hayes‐Jordan A. , Green H. , Ludwig J. , Anderson P. 
Published: April 2012

AbstractBackgroundIntra‐abdominal metastasis is a rare form of tumor dissemination in children. Complete surgical resection is usually deemed impossible. Children are frequently offered palliative care only. We adopted an aggressive approach for these cases which includes removal of dozens to hundreds of tumor nodules followed by perfusion of the abdominal cavity with hyperthermic chemotherapy (HIPEC) with a curative intent.MethodsWe evaluated toxicity in 23 children and young adults undergoing 27 HIPEC procedures using cisplatin. Disease diagnoses included rhabdomyosarcoma (RMS), non‐RMS soft tissue sarcoma, (NRSTS), desmoplastic small round cell tumor, (DSRCT), mesothelioma, Wilms tumor, melanomatosis, and adenocarcinoma. Patients underwent cytoreductive surgery followed by cisplatin at 40.5–41°C, for 90 minutes. A subset of these patients was enrolled on our phase 1 study and as part of dose escalation cohort received 150 mg/m2 of cisplatin. All toxicities were recorded.ResultsMaximum tolerated dose was 100 mg/m2. Dose limiting toxicity was grade 3 renal failure. In five of 27, 18% had grade 3 or higher renal failure. One patient developed a subclinical decrease in hearing and there were 2 grade 3 hematologic toxicities, 2 grade 3 hepatic toxicities, and one grade 3 ileus. One patient suffered grade3 cardiotoxicity. There were no operative/perioperative mortalities. Surgical complications occurred in 5/27 (18%) of patients. With a follow‐up of 6–60 months, seven patients (26%) had no recurrence.ConclusionsHIPEC is reasonably tolerated in pediatric patients with extensive abdominal metastasis. More study is needed to determine for which histologies HIPEC is most efficacious. Pediatr Blood Cancer 2012;59:395–397. © 2012 Wiley Periodicals, Inc.
Pharmacoepidemiology: defining the field and its core content
Authors: Jones Judith K. , Tilson Hugh H. , Lewis James D. 
Published: April 2012

ABSTRACTPurposeEmerging interests in pharmacoepidemiology make it important to define the profession's core content. The International Society for Pharmacoepidemiology (ISPE)'s Education Committee sought to develop a consensus on its core disciplines. This report recapitulates their efforts and conclusions.MethodsThe survey for skill inventories conducted characterized the field of pharmacoepidemiology by five categories of core competency/knowledge (pharmacovigilance, exposure data, epidemiology, clinical pharmacology, and medical product regulation) plus communication and leadership in these areas. It was sent to pharmacoepidemiology units within the industry, academia, and government representing the membership worldwide.ResultsAfter three waves, 125 members responded (~10% of the membership). Respondents were from North America (61%), European Union (23%), and the remainder from Asian Pacific and South American regions, representing the full spectrum of ISPE membership. Pharmacovigilance, analysis of exposure data, epidemiologic methods, and communication skills were the competencies identified as essential. Fourteen competencies were judged to be “essential” by >80% of the respondents; a further 26 had “essential” as the most frequently rated category but represented <80% of the respondents. Six items had “desirable but not a core competency” as the most commonly selected. None of the proposed competencies scored as “not a core competency” by >25% of the respondents. Only five of the competencies were suggested as “not core” by 10% or more.ConclusionsThis survey identified a wide range of content relevant to the field of pharmacoepidemiology. This list will likely evolve over time. A curriculum around these areas will help prepare the next generation of pharmacoepidemiologists. Copyright © 2012 John Wiley & Sons, Ltd.
Best in class: A classroom‐based model for ameliorating problem behavior in early childhood settings
Authors: Vo Abigail K. , Sutherland Kevin S. , Conroy Maureen A. 
Published: April 2012

AbstractAs more young children enter school settings to attend early childhood programs, early childhood teachers and school psychologists have been charged with supporting a growing number of young children with chronic problem behaviors that put them at risk for the development of emotional/behavioral disorders (EBDs). There is a need for effective, feasible models that help school personnel address the needs of these young children within early childhood settings. This article describes Behavioral, Emotional, and Social Training: Competent Learners Achieving School Success (BEST in CLASS). BEST in CLASS is a classroom‐based intervention designed to help early childhood teachers master effective instructional strategies for preventing and ameliorating problem behavior in young children at risk for EBDs through a teacher training and performance‐based coaching model. The BEST in CLASS intervention model is described, and preliminary data are presented, followed by a discussion of implications for practice and future research directions. © 2012 Wiley Periodicals, Inc.
The toxin–antitoxin proteins relBE2Spn of Streptococcus pneumoniae: Characterization and association to their DNA target
Authors: Moreno‐Córdoba Inma , Diago‐Navarro Elizabeth , Barendregt Arjan , Heck Albert J. R. , Alfonso Carlos , Díaz‐Orejas Ramón , Nieto Concha , Espinosa Manuel 
Published: April 2012

AbstractThe chromosome of the pathogenic Gram‐positive bacterium Streptococcus pneumoniae contains between six to 10 operons encoding toxin–antitoxin systems (TAS). TAS are widespread and redundant in bacteria and archaea and their role, albeit still obscure, may be related to important aspects of bacteria lifestyle like response to stress. One of the most abundant TAS is the relBE family, being present in the chromosome of many bacteria and archaea. Because of the high rates of morbility and mortality caused by S. pneumoniae, it has been interesting to gain knowledge on the pneumococcal TAS, among them the RelBE2Spn proteins. Here, we have analyzed the DNA binding capacity of the RelB2Spn antitoxin and the RelB2Spn‐RelE2Spn proteins by band‐shift assays. Thus, a DNA region encompassing the operator region of the proteins was identified. In addition, we have used analytical ultracentrifugation and native mass spectrometry to measure the oligomerization state of the antitoxin alone and the RelBE2Spn complex in solution bound or unbound to its DNA substrate. Using native mass spectrometry allowed us to unambiguously determine the stoichiometry of the RelB2Spn and of the RelBE2Spn complex alone or associated to its DNA target.Proteins 2012; © 2012 Wiley Periodicals, Inc.
Large loop conformation sampling using the activation relaxation technique, ART‐nouveau method
Authors: St‐Pierre Jean‐François , Mousseau Normand 
Published: April 2012

AbstractWe present an adaptation of the ART‐nouveau energy surface sampling method to the problem of loop structure prediction. This method, previously used to study protein folding pathways and peptide aggregation, is well suited to the problem of sampling the conformation space of large loops by targeting probable folding pathways instead of sampling exhaustively that space. The number of sampled conformations needed by ART nouveau to find the global energy minimum for a loop was found to scale linearly with the sequence length of the loop for loops between 8 and about 20 amino acids. Considering the linear scaling dependence of the computation cost on the loop sequence length for sampling new conformations, we estimate the total computational cost of sampling larger loops to scale quadratically compared to the exponential scaling of exhaustive search methods. Proteins 2012; © 2012 Wiley Periodicals, Inc.