bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Berlin Heart EXCOR Pediatrics—The SickKids Experience 2004–2008
Authors: Humpl Tilman , Furness Sarah , Gruenwald Colleen , Hyslop Cecilia , Van Arsdell Glen 
Published: June 2010

AbstractThe ventricular assist device (VAD) Berlin Heart EXCOR Pediatrics was utilized at our institution since 2004 for bridging pediatric patients to cardiac transplantation or myocardial recovery. The present study reviewed our results following VAD implantation. We retrospectively reviewed patients that underwent implantation of a VAD between October 2004 and October 2008. Data collected included age at implantation, gender, weight, underlying disease, pre‐ and postdevice clinical status, complications, and outcome. Fifteen patients were identified (9 female and 6 male, average age: 8.8 years, range 0.3–14.8; average weight 31.1 kg, range 5.2–86.4). Indications for VAD support were dilated cardiomyopathy in 14 patients and progressing heart failure with a single ventricle physiology (bidirectional Glenn shunt) in one patient. Three patients (20%) were bridged from extracorporeal membrane oxygenation to VAD. Average support was 29 (1–108) days. Fourteen patients were on a bi‐VAD, one patient (single ventricle) had single VAD support. Three patients developed mediastinal/pericardial fluid collections, requiring surgical exploration in two, and drain insertion in one. Three patients presented with neurological symptoms. In two patients, a total of three blood pumps were exchanged due to thrombus formation. No patient was weaned off the VAD; two patients (13%) died on the VAD. All surviving patients are neurologically intact at follow‐up. In our experience, VAD support provides an effective means of bridging children with advanced dilated cardiomyopathy or heart failure to transplantation with a relatively small number of complications and deaths given the complexity of the patient population.
Hospitalization in Community‐Dwelling Persons with Alzheimer's Disease: Frequency and Causes
Authors: Rudolph James L. , Zanin Nicole M. , Jones Richard N. , Marcantonio Edward R. , Fong Tamara G. , Yang Frances M. , Yap Liang , Inouye Sharon K. 
Published: June 2010

OBJECTIVES: To examine the rates of and risk factors for acute hospitalization in a prospective cohort of older community‐dwelling patients with Alzheimer's disease (AD).DESIGN: Longitudinal patient registry.SETTING: AD research center.PARTICIPANTS: Eight hundred twenty‐seven older persons with AD.MEASUREMENTS: Acute hospitalization after AD research center visit was determined from a Medicare database. Risk factor variables included demographics, dementia‐related, comorbidity and diagnoses and were measured in interviews and according to Medicare data.RESULTS: Of the 827 eligible patients seen at the ADRC during 1991 to 2006 (median follow‐up 3.0 years), 542 (66%) were hospitalized at least once, and 389 (47%) were hospitalized two or more times, with a median of 3 days spent in the hospital per person‐year. Leading reasons for admission were syncope or falls (26%), ischemic heart disease (17%), gastrointestinal disease (9%), pneumonia (6%), and delirium (5%). Five significant independent risk factors for hospitalization were higher comorbidity (hazard ratio (HR)=1.87, 95% confidence interval (CI)=1.57–2.23), previous acute hospitalization (HR=1.65, 95% CI=1.37–1.99), older age (HR=1.51, 95% CI=1.26–1.81), male sex (HR=1.27, 95% CI=1.04–1.54), and shorter duration of dementia symptoms (HR=1.26, 95% CI=1.02–1.56). Cumulative risk of hospitalization increased with number of risk factors present at baseline: 38% with zero factors, 57% with one factor, 70% with two or three factors, and 85% with four or five factors (Ptrend<.001).CONCLUSION: In a community‐dwelling population with generally mild AD, hospitalization is frequent, occurring in two‐thirds of participants over a median follow‐up time of 3 years. With these results, clinicians may be able to identify dementia patients at high risk for hospitalization.
Catheter Ablation of Atrial Fibrillation in Patients With Valvular Heart Disease: Long‐Term Follow‐Up Results
Authors: MIYAZAKI SHINSUKE , KUWAHARA TAISHI , KOBORI ATSUSHI , TAKAHASHI YOSHIHIDE , TAKEI ASUMI , SATO AKIRA , ISOBE MITSUAKI , TAKAHASHI ATSUSHI 
Published: June 2010

AF Ablation in Patients With Valvular Heart Disease. Background: The purpose of this study is to evaluate the efficacy of atrial fibrillation (AF) ablation in patients with moderate valvular heart disease (VHD).
Methods:
In total, 534 consecutive patients who underwent AF ablation were enrolled. Patients with a history of valve surgery or other structural heart disease were excluded. Patients with clinically moderate VHD (group‐1, n = 45) were compared with those without VHD (control group‐2, n = 436). Ipsilateral pulmonary vein antrum isolation (PVAI) was performed with a double Lasso technique in all the patients. Left atrial (LA) linear ablation was undertaken in persistent AF patients, if AF was inducible after PVAI.
Results:
Patients in group‐1 were significantly older and had a larger LA. PVAI was successfully achieved in all the patients. Patients in group‐1 received LA linear ablation more frequently during the index procedure. After a median of 26 months from the index procedure, the freedom from AF was significantly lower in group‐1 than group‐2 off antiarrhythmic drugs (AADs) (47% vs 69%, P = 0.002). Although there were more number of total procedures in group‐1 than group‐2, the freedom from AF was lower at median 24 months after the last procedure (78% vs 87%, P = 0.038). There was no significant difference in the freedom from AF on AADs (91% vs 95%, P = 0.356) or complication rate between the 2 groups. Atrial tachycardia following the index procedure was observed more frequently in group‐1 (P = 0.001).
Conclusion:
The patients with VHD undergoing AF ablation are less likely to remain in sinus rhythm at long term without AADs than those without VHD. (J Cardiovasc Electrophysiol, Vol. 21, pp. 1193‐1198, November 2010)
Tissue‐engineered ligament: implant constructs for tooth replacement
Authors: Gault Philippe , Black Annie , Romette Jean‐Louis , Fuente Fabien , Schroeder Klaus , Thillou Fabienne , Brune Thierry , Berdal Ariane , Wurtz Tilmann 
Published: June 2010

Gault P, Black A, Romette J‐L, Fuente F, Schroeder K, Thillou F, Brune T, Berdal A, Wurtz T. Tissue‐engineered ligament: implant constructs for tooth replacement. J Clin Periodontol 2010. 37: 750‐758 doi: 10.1111/j.1600-051X.2010.01588.x.AbstractAim: A tissue‐engineered periodontal ligament (PDL) around implants would represent an important new therapeutic tool to replace lost teeth. The PDL is the key to tooth anchoring; it connects tooth root and alveolar bone, and it sustains bone formation.Materials and Methods: Cells were isolated from PDL and cultured in a bioreactor on titanium pins. After the formation of multiple cellular layers, pins were implanted in enlarged dental alveolae.Main Outcome Measures: Cell‐covered implants integrated without adverse effects, and induced bone in their vicinity.Results: A histological examination of a dog model revealed that cells were arranged in a typical ligament‐like fashion. In human patients, product safety was ascertained for 6–60 months. Probing and motility assessments suggested that the implants were well integrated with mechanical properties similar to those of teeth. Radiographs demonstrated the regeneration of deficient alveolar bone, the development of a lamina dura adjacent to a mineral‐devoid space around the implant and implant migration in an intact bone structure.Conclusions: New tissue consistent with PDL developed on the surface of dental implants after implantation. This proof‐of‐principal investigation demonstrates the application of ligament‐anchored implants, which have potential advantages over osseointegrated oral implants.
Audiovisual Interventions to Reduce the Use of General Anaesthesia with Paediatric Patients during Radiation Therapy
Authors: Willis D , Barry P 
Published: June 2010

SummaryClinical audiovisual interventions were implemented to avoid the use of general anaesthesia with children undergoing radiation therapy treatment. A retrospective audit and case study review was conducted to evaluate the utility of distraction interventions aimed at improving immobilisation and reducing separation anxiety for children aged between 2 and 6 years old who received radiation therapy. A simple, inexpensive audiovisual system was established using commercially available equipment. Paediatric patients could elect to (i) use a closed‐circuit TV system that allowed them to see their carer(s); (ii) watch a DVD movie; or (iii) listen to carer(s) on a microphone during their treatment. Over a 2‐year period (March 2007–May 2009), 37 paediatric patients aged 2–6 years received radiation therapy at the centre. Twenty‐four children participated in audiovisual interventions, and 92% (n = 22) of these children did not require the use of general anaesthesia for some or all of their treatment. Case study review illustrates the utility and limitations of the system. The audit and case studies suggest that the audiovisual interventions provided supportive care and reduced the need to anaesthetise children undergoing radiation therapy treatment.
The Discovery of Zinc Fingers and Their Applications in Gene Regulation and Genome Manipulation
Authors: Klug Aaron 
Published: June 2010

An account is given of the discovery of the classical Cys2His2 zinc finger, arising from the interpretation of biochemical studies on the interaction of the Xenopus protein transcription factor IIIA with 5S RNA, and of structural studies on its structure and its interaction with DNA. The finger is a self-contained domain stabilized by a zinc ion ligated to a pair of cysteines and a pair of histidines, and by an inner hydrophobic core. This discovery showed not only a new protein fold but also a novel principle of DNA recognition. Whereas other DNA binding proteins generally make use of the two-fold symmetry of the double helix, zinc fingers can be linked linearly in tandem to recognize nucleic acid sequences of varying lengths. This modular design offers a large number of combinatorial possibilities for the specific recognition of DNA (or RNA). It is therefore not surprising that the zinc finger is found widespread in nature, including 3% of the genes of the human genome. The zinc finger design is ideally suited for engineering proteins to target specific genes. In the first example of their application in 1994, a three-finger protein was constructed to block the expression of an oncogene transformed into a mouse cell line. In addition, a reporter gene was activated by targeting an inserted zinc finger promoter. Thus, by fusing zinc finger peptides to repression or activation domains, genes can be selectively switched off or on. It was also suggested that by combining zinc fingers with other effector domains, e.g., from nucleases or integrases, to form chimeric proteins, genomes could be manipulated or modified. Several applications of such engineered zinc finger proteins are described here, including some of therapeutic importance.
From Virus Structure to Chromatin: X-ray Diffraction to Three-Dimensional Electron Microscopy
Authors: Klug Aaron 
Published: June 2010

Early influences led me first to medical school with a view to microbiology, but I felt the lack of a deeper foundation and changed to chemistry, which in turn led me to physics and mathematics. I moved to the University of Cape Town to work on the X-ray crystallography of some small organic compounds. I developed a new method of using molecular structure factors to solve the crystal structure, which won me a research studentship to Trinity College Cambridge and the Cavendish Laboratory. There I worked on the austenite-pearlite transition in steel. This is governed by the dissipation of latent heat, and I ended up numerically solving partial differential equations. I used the idea of nucleation and growth during the phase change, which had its echo when I later tackled the assembly of Tobacco mosaic virus (TMV) from its constituent RNA and protein subunits. I wanted to move on to X-ray structure analysis of large biological molecules and obtained a Nuffield Fellowship to work in J.D. Bernal's department at Birkbeck College, London. There, I met Rosalind Franklin, who had taken up the study of TMV. I was able to interpret some of Franklin's beautiful X-ray diffraction patterns of the virus particle. From then on, my fate was sealed. After Franklin's untimely death in 1958, I moved in 1962 to the newly built MRC Laboratory of Molecular Biology in Cambridge, which, under Max Perutz, housed the original MRC unit from the Cavendish Laboratory. I was thus privileged to join the Laboratory at an early stage in its expansion and consequently able to take advantage of, and to help build up, its then unique environment of intellectual and technological sophistication. There I have remained ever since.
Direct Inhibition of Elastase Activity by Indole-3-Carbinol Triggers a CD40-TRAF Regulatory Cascade That Disrupts NF-κB Transcriptional Activity in Human Breast Cancer Cells
Authors: Aronchik Ida , Bjeldanes Leonard F. , Firestone Gary L. 
Published: June 2010

AbstractTreatment of highly tumorigenic MDA-MB-231 human breast cancer cells with indole-3-carbinol (I3C) directly inhibited the extracellular elastase-dependent cleavage of membrane-associated CD40, a member of the tumor necrosis factor (TNF) receptor superfamily. CD40 signaling has been implicated in regulating cell survival, apoptosis, and proliferation, as well as in sensitizing breast cancer cells to chemotherapy, and is therefore an important potential target of novel breast cancer treatments. The I3C-dependent accumulation of full-length unprocessed CD40 protein caused a shift in CD40 signaling through TNF receptor–associated factors (TRAF), including the TRAF1/TRAF2 positive regulators and TRAF3 negative regulator of NF-κB transcription factor activity. Because TRAF1 is a transcriptional target gene of NF-κB, I3C disrupted a positive feedback loop involving these critical cell survival components. siRNA ablation of elastase expression mimicked the I3C inhibition of CD40 protein processing and G1 cell cycle arrest, whereas siRNA knockdown of TRAF3 and the NF-κB inhibitor IκB prevented the I3C-induced cell cycle arrest. In contrast, siRNA knockdown of PTEN had no effect on the I3C control of NF-κB activity, showing the importance of CD40 signaling in regulating this transcription factor. Our study provides the first direct in vitro evidence that I3C directly inhibits the elastase-mediated proteolytic processing of CD40, which alters downstream signaling to disrupt NF-κB–induced cell survival and proliferative responses. Furthermore, we have established a new I3C-mediated antiproliferative cascade that has significant therapeutic potential for treatment of human cancers associated with high levels of elastase and its CD40 membrane substrate. Cancer Res; 70(12); 4961–71. ©2010 AACR.
Increased Immunogenicity of Tumor-Associated Antigen, Mucin 1, Engineered to Express α-Gal Epitopes: A Novel Approach to Immunotherapy in Pancreatic Cancer
Authors: Deguchi Takashi , Tanemura Masahiro , Miyoshi Eiji , Nagano Hiroaki , Machida Tomohiko , Ohmura Yoshiaki , Kobayashi Shogo , Marubashi Shigeru , Eguchi Hidetoshi , Takeda Yutaka , Ito Toshinori , Mori Masaki , Doki Yuichiro , Sawa Yoshiki 
Published: June 2010

Abstract
Mucin 1 (MUC1), a bound mucin glycoprotein, is overexpressed and aberrantly glycosylated in &gt;80% of human ductal pancreatic carcinoma. Evidence suggests that MUC1 can be used as a tumor marker and is a potential target for immunotherapy of pancreatic cancer. However, vaccination with MUC1 peptides fails to stimulate the immune response against cancer cells because immunity toward tumor-associated antigens (TAA), including MUC1, in cancer patients is relatively weak, and the presentation of these TAAs to the immune system is poor due to their low immunogenicity. We investigated whether vaccination with immunogenetically enhanced MUC1 (by expressing α-gal epitopes; Galα1-3Galβ1-4GlcNAc-R) can elicit effective antibody production for MUC1 itself as well as certain TAAs derived from pancreatic cancer cells and induced tumor-specific T-cell responses. We also used α1,3galactosyltransferase (α1,3GT) knockout mice that were preimmunized with pig kidney and transplanted with B16F10 melanoma cells transfected with MUC1 expression vector. Vaccination of these mice with α-gal MUC1 resulted in marked inhibition of tumor growth and significant improvement of overall survival time compared with mice vaccinated with MUC1 alone (P = 0.003). Furthermore, vaccination with pancreatic cancer cells expressing α-gal epitopes induced immune responses against not only differentiated cancer cells but also cancer stem cells. The results suggested that vaccination using cells engineered to express α-gal epitopes is a novel strategy for treatment of pancreatic cancer. Cancer Res; 70(13); 5259–69. ©2010 AACR.
High Wnt Signaling Represses the Proapoptotic Proteoglycan syndecan-2 in Osteosarcoma Cells
Authors: Dieudonné François-Xavier , Marion Allison , Haÿ Eric , Marie Pierre Jacques , Modrowski Dominique 
Published: June 2010

Abstract
Osteosarcoma is characterized by frequent relapse and metastatic disease associated with resistance to chemotherapy. We previously showed that syndecan-2 is a mediator of the antioncogenic effect of chemotherapeutic drugs. The purpose of this work was to elucidate molecular mechanisms responsible for the low expression of syndecan-2 in osteosarcoma. We compared the regulatory activity of cis-acting DNA sequences of the syndecan-2 gene in osteosarcoma and osteoblastic cell lines. We identified a DNA region that negatively regulates syndecan-2 transcription in the osteosarcoma cells. T-cell factors (TCF) bind to this sequence in vivo. Wnt3a stimulation, β-catenin activation, and TCF overexpression resulted in syndecan-2 repression, whereas Wnt inhibition using sFRP-1 increased syndecan-2 expression in U2OS cells. RhoA activation blunted the stimulatory effect of sFRP-1 on syndecan-2 transcription, whereas RhoA inhibition enhanced syndecan-2 expression. These results indicate that Wnt/β-catenin and Wnt/RhoA signaling contribute to syndecan-2 repression. The alteration of syndecan-2 expression in osteosarcoma cell lines also seemed to be related to a higher shedding, controlled by Wnt/RhoA. Conversely, syndecan-2 was found to activate its own expression in U2OS cells through RhoA inhibition. These data identify a molecular network that may contribute to the low expression of the proapoptotic proteoglycan syndecan-2 in osteosarcoma cells. The high activity of the canonical Wnt pathway in the different osteosarcoma cells induces a constitutive repression of syndecan-2 transcription, whereas Wnt/RhoA signaling blocks the amplification loop of syndecan-2 expression. Our results identify syndecan-2 as a Wnt target and bring new insights into a possible pathologic role of Wnt signaling in osteosarcoma. Cancer Res; 70(13); 5399–408. ©2010 AACR.
Development of Human Single-Chain Antibodies to the Transferrin Receptor that Effectively Antagonize the Growth of Leukemias and Lymphomas
Authors: Crépin Ronan , Goenaga Anne-Laure , Jullienne Betsy , Bougherara Houcine , Legay Christine , Benihoud Karim , Marks James D. , Poul Marie-Alix 
Published: June 2010

Abstract
The major route of iron uptake by cells occurs through transferrin receptor (TfR)–mediated endocytosis of diferric-charged plasma transferrin (holo-Tf). In this work, we pursued TfR antibodies as potential cancer therapeutics, characterizing human single-chain variable antibody fragments (scFv) specific for the human TfR isolated from a phage display library. We hypothesized that many of these antibodies would function as ligand mimetics because scFvs from the library were selected for binding and internalization into living cells. In support of this hypothesis, the anti-TfR scFvs identified were antagonists of TfR binding to holo-Tf, particularly two of the most potent antibodies, 3TF12 and 3GH7, which blocked the in vitro proliferation of a number of hematopoietic cancer cell lines. We optimized this activity of 3TF12 and 3GH7 by engineering 55-kDa bivalent antibody formats, namely, F12CH and H7CH, which could block cell proliferation with an IC50 of 0.1 μg/mL. We found that the mechanism of the scFv antibody cytotoxicity was unique compared with cytotoxic anti-TfR monoclonal antibodies that have been described, causing cell surface upregulation of TfR along with the inhibition of holo-Tf cell uptake and induction of cell death. In a nude mouse model of erythroleukemia, administration of F12CH reduced tumor growth. Together, our findings define a new class of fully human anti-TfR antibodies suitable for immunotherapy against tumors whose proliferation relies on high levels of TfR and iron uptake, such as acute lymphoid and myeloid leukemias. Cancer Res; 70(13); 5497–506. ©2010 AACR.
Drug-Induced Vessel Remodeling in Bone Metastases as Assessed by Dynamic Contrast Enhanced Magnetic Resonance Imaging and Vessel Size Imaging: A LongitudinalIn vivoStudy
Authors: Bäuerle Tobias , Merz Maximilian , Komljenovic Dorde , Zwick Stefan , Semmler Wolfhard 
Published: June 2010

AbstractPurpose: The aim of this study was to assess the antiangiogenic treatment effects of zoledronic acid (ZA) and sunitinib malate (SM) noninvasively in experimental breast cancer bone metastases by dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and vessel size imaging.Experimental Design: Nude rats bearing bone metastases after inoculation of MDA-MB-231 breast cancer cells were treated with ZA (40 μg/kg weekly; n = 8 rats), SM (20 mg/kg daily; n = 8 rats), or their combination (ZA and SM; n = 8 rats) and compared with sham-treated controls (n = 10 rats). Vascular changes in bone metastases were longitudinally imaged in vivo using DCE-MRI [amplitude (A) and exchange rate coefficient (kep)] and vessel size imaging [blood volume (BV) and vessel size index (VI)]. In addition, antiresorptive and antitumor changes were assessed in these lesions by flat-panel volumetric computed tomography as well as morphologic MRI and diffusion-weighted imaging.Results: In bone metastases, significant changes in A, kep, BV, and VI in accordance with decreased blood volume and vessel permeability as well as with increased mean vessel diameters were observed after application of ZA and SM as compared with controls. In this longitudinal study, antiangiogenic changes preceded the inhibition of osteolysis and antitumor effects after treatment.Conclusions: These results indicate vessel remodeling in breast cancer bone metastases on ZA and SM treatment and implicate substantial effects on imaging and treatment of malignant bone lesions. Clin Cancer Res; 16(12); 3215–25. ©2010 AACR.