bluuebunny/crossref_metadata_2025_split huggingface dataset:
Fanconi anemia D2 protein is an apoptotic target mediated by caspases
Authors: Park Su‐Jung , Beck Brian D. , Saadatzadeh M. Reza , Haneline Laura S. , Clapp D. Wade , Lee Suk‐Hee 
Published: April 2011

AbstractFANCD2, a key factor in the FANC‐BRCA1 pathway is monoubiquitinated and targeted to discrete nuclear foci following DNA damage. Since monoubiquitination of FANCD2 is a crucial indicator for cellular response to DNA damage, we monitored the fate of FANCD2 and its monoubiquitination following DNA damage. Disappearance of FANCD2 protein was induced following DNA damage in a dose‐dependent manner, which correlated with degradation of BRCA1 and poly‐ADP ribose polymerase (PARP), known targets for caspase‐mediated apoptosis. Disappearance of FANCD2 was not affected by a proteasome inhibitor but was blocked by a caspase inhibitor. DNA damage‐induced disappearance of FANCD2 was also observed in cells lacking FANCA, suggesting that disappearance of FANCD2 does not depend on FANC‐BRCA1 pathway and FANCD2 monoubiquitination. In keeping with this, cells treated with TNF‐α, an apoptotic stimulus without causing any DNA damage, also induced disappearance of FANCD2 without monoubiquitination. Together, our data suggest that FANCD2 is a target for caspase‐mediated apoptotic pathway, which may be an early indicator for apoptotic cell death. J. Cell. Biochem. 112: 2383–2391, 2011. © 2011 Wiley‐Liss, Inc.
Motive‐oriented therapeutic relationship in brief psychodynamic intervention for patients with depression and personality disorders
Authors: Kramer Ueli , Rosciano Alessandra , Pavlovic Mirjana , Berthoud Laurent , Despland Jean‐Nicolas , de Roten Yves , Caspar Franz 
Published: April 2011

AbstractMotive‐Oriented Therapeutic Relationship (MOTR, also called Complementary Therapeutic Relationship) has already shown itself to be related to therapeutic outcome in several studies. The present study aims to test MOTR in a 4‐session Brief Psychodynamic Intervention for patients presenting with major depressive disorder (MDD) and comorbid personality disorder (PD). In total, N = 20 patients were selected; n = 10 had MDD, n = 10 had MDD with comorbid PD. The first therapy session was videotaped and analyzed by means of Plan Analysis and the MOTR scale. Results suggest a differential effect on outcome: only the nonverbal component of MOTR is related to symptomatic change in patients presenting with MDD and comorbid PD; no such effect was found for patients with MDD alone. These results are discussed in line with the generalization and refinement of the conclusions of previous findings on the MOTR. © 2011 Wiley Periodicals, Inc. J Clin Psychol 67:1–11, 2011.
P‐glycoprotein mediates resistance to A3 adenosine receptor agonist 2‐chloro‐N6‐(3‐iodobenzyl)‐adenosine‐5′‐n‐methyluronamide in human leukemia cells
Authors: Mlejnek Petr , Dolezel Petr , Kosztyu Petr 
Published: April 2011

AbstractWe studied effects of 2‐chloro‐N6‐(3‐iodobenzyl)‐adenosine‐5′‐N‐methyluronamide (Cl‐IB‐MECA) on apoptosis induction in the K562/Dox cell line, which overexpressed P‐glycoprotein (P‐gp, ABCB1, MDR1). We found that the K562/Dox cell line was significantly more resistant to Cl‐IB‐MECA than the maternal cell line K562, which did not express P‐gp. Although both cell lines expressed the A3 adenosine receptor (A3AR), cytotoxic effects of Cl‐IB‐MECA were not prevented by its selective antagonist MRS1523 (3‐propyl‐6‐ethyl‐5‐[(ethylthio)carbonyl]‐2 phenyl‐4‐propyl‐3‐pyridine carboxylate). Analysis of cell extracts revealed that the intracellular level of Cl‐IB‐MECA was significantly lower in the K562/Dox cell line than in the maternal cell line K562. The downregulation of P‐gp expression using shRNA targeting ABCB1 gene led to increased intracellular level of Cl‐IB‐MECA and restored cell sensitivity to this drug. Similarly, valspodar (PSC‐833), a specific inhibitor of P‐gp, restored sensitivity of the K562/Dox cell line to Cl‐IB‐MECA with concomitant increase of intracellular level of Cl‐IB‐MECA in the resistant cell line, while it affected cytotoxicity of Cl‐IB‐MECA in the sensitive cell line only marginally. An enzyme based assay provided evidence for interaction of P‐gp with Cl‐IB‐MECA. We further observed that cytotoxic effects of Cl‐IB‐MECA could be augmented by activation of extrinsic cell death pathway by Apo‐2L (TRAIL) but not FasL or TNF‐α. Our results revealed that Cl‐IB‐MECA induced an increase in expression of TRAIL receptors in K562 cells, which could sensitize cells to apoptosis induction via an extrinsic cell death pathway. Importantly, these effects were inversely related to P‐gp expression. In addition, MRS1523 did not affect Cl‐IB‐MECA induced expression of TRAIL receptors. J. Cell. Physiol. 227: 676–685, 2012. © 2011 Wiley Periodicals, Inc.
Human β‐defensins differently affect proliferation, differentiation, and mineralization of osteoblast‐like MG63 cells
Authors: Kraus D. , Deschner J. , Jäger A. , Wenghoefer M. , Bayer S. , Jepsen S. , Allam J. P. , Novak N. , Meyer R. , Winter J. 
Published: April 2011

AbstractPurpose of this study was to investigate whether human β‐defensins (hBDs) affect maturation and proliferation of osteoblast‐like MG63 cells in vitro. Osteoblast‐like MG63 cells were stimulated with hBD‐1, ‐2, and ‐3 under control conditions and with hBD‐2 during experimental inflammation (induced by interleukin‐1β, tumor necrosis factor‐α, toll‐like receptor‐2 and ‐4 agonists). Expression of different osteogenic markers and hBDs were analyzed by real‐time PCR, immunohistochemistry, and enzyme‐linked immunosorbent assay. In addition, alkaline phosphatase (ALP) enzyme activity and biomineralization as markers for differentiation were monitored. All tested hBDs were expressed on mRNA and protein level in MG63 cells. Only stimulation with hBD‐2 elevated the proliferation rate. hBD‐2 and hBD‐3 positively affected the differentiation of osteoblast‐like cells provided by increased transcript levels of osteogenic markers, up‐regulated ALP enzyme activity and enhanced mineralized nodule formation. All pro‐inflammatory stimuli enhanced interleukin‐6 and hBD‐2 expression and down‐regulated markers of osteoblastic differentiation. In accordance, inflammation increased transcript level of Notch‐1 (an inhibitor of osteoblastic differentiation). hBD‐2 was not able to revert effects of inflammation on differentiation. In bone cells human β‐defensins exhibit further functions than antimicrobial peptide activity. These include stimulation of proliferation and differentiation. Differentiation arrest due to inflammation could not be overcome by hBD‐2 alone. J. Cell. Physiol. 227: 994–1003, 2012. © 2011 Wiley Periodicals, Inc.
Enhanced lipid—but not carbohydrate—supported mitochondrial respiration in skeletal muscle of PGC‐1α overexpressing mice
Authors: Hoeks Joris , Arany Zolt , Phielix Esther , Moonen‐Kornips Esther , Hesselink Matthijs K.C. , Schrauwen Patrick 
Published: April 2011

AbstractSkeletal muscle mitochondrial dysfunction has been linked to several disease states as well as the process of aging. A possible factor involved is the peroxisome proliferator‐activated receptor (PPAR) γ co‐activator 1α (PGC‐1α), a major player in the regulation of skeletal muscle mitochondrial metabolism. However, it is currently unknown whether PGC‐1α, besides stimulating mitochondrial proliferation, also affects the functional capacity per mitochondrion. Therefore, we here tested whether PGC‐1α overexpression, besides increasing mitochondrial content, also leads to intrinsic mitochondrial adaptations. Skeletal muscle mitochondria from 10 male, muscle‐specific PGC‐1α overexpressing mice (PGC‐1αTg) and 8 wild‐type (WT) mice were isolated. Equal mitochondrial quantities were then analyzed for their oxidative capacity by high‐resolution respirometry, fuelled by a carbohydrate‐derived (pyruvate) and a lipid (palmitoyl‐CoA plus carnitine) substrate. Additionally, mitochondria were tested for reactive oxygen species (superoxide) production and fatty acid (FA)‐induced uncoupling. PGC‐1αTg mitochondria were characterized by an improved intrinsic mitochondrial fat oxidative capacity as evidenced by pronounced increase in ADP‐stimulated respiration (P < 0.001) and maximal uncoupled respiration (P < 0.001) upon palmitoyl‐CoA plus carnitine. Interestingly, intrinsic mitochondrial capacity on a carbohydrate‐derived substrate tended to be reduced. Furthermore, the sensitivity to FA‐induced uncoupling was diminished in PGC‐1αTg mitochondria (P = 0.02) and this was accompanied by a blunted reduction in mitochondrial ROS production upon FAs in PGC‐1αTg versus WT mitochondria (P = 0.04). Uncoupling protein 3 (UCP3) levels were markedly reduced in PGC‐1αTg mitochondria (P < 0.001). Taken together, in addition to stimulating mitochondrial proliferation in skeletal muscle, we show here that overexpression of PGC‐1α leads to intrinsic mitochondrial adaptations that seem restricted to fat metabolism. J. Cell. Physiol. 227: 1026–1033, 2012. © 2011 Wiley Periodicals, Inc.
Switching the fiber knob of oncolytic adenoviruses to avoid neutralizing antibodies in human cancer patients
Authors: Raki Mari , Sarkioja Merja , Escutenaire Sophie , Kangasniemi Lotta , Haavisto Elina , Kanerva Anna , Cerullo Vincenzo , Joensuu Timo , Oksanen Minna , Pesonen Sari , Hemminki Akseli 
Published: April 2011

AbstractBackgroundOncolytic adenoviruses are an attractive strategy for treating cancers resistant to conventional treatments. However, their systemic utility could be limited as a result of the high prevalence of pre‐existing immunity towards the vector. Furthermore, neutralizing antibodies (NAbs) may prevent successful intravenous readministration of the same agent. Previous preclinical reports indicate that the NAb response can be partially overcome by modifying the adenoviral fiber knob. However, to date, this strategy has not been evaluated in human patients.MethodsTwenty‐four human patients with advanced cancer were treated with two cycles of oncolytic adenoviruses, featuring three capsid variants: unmodified adenovirus serotype 5 (Ad5), serotype 5 with RGD motif in the HI‐loop of the fiber knob (Ad5‐RGD) and serotype 5 carrying fiber knob from serotype 3 (Ad5/3). A virus with different fiber structure was used for the second round of treatment and patient serum was analyzed for a neutralizing effect.ResultsAll patients developed NAbs against the virus that they were treated with. However, the magnitude and velocity of the response varied considerably. When measured just before the second treatment cycle, a differential in serum NAb titer against the first versus second virus was seen in 83% of cases, suggesting that even minor changes in the fiber knob can circumvent neutralization in cancer patients. No correlation between NAb titers and outcome variables was observed.ConclusionsThe results obtained in the present study extend previous preclinical reports into human cancer patients and suggest that modification of the fiber knob is a feasible strategy for circumventing the NAb response in patients receiving multiple rounds of oncolytic adenoviruses. Copyright © 2011 John Wiley & Sons, Ltd.
ESI‐MS quantitation of iron as its 4‐(2‐pyridylazo)resorcinol (PAR) complex: application to pharmaceutical tablets containing iron oxide pigment
Authors: Susanto Dendi , English Ann M. , Sharma Ravi , Kwong Elizabeth 
Published: April 2011

AbstractQuantitation of iron oxide (Fe2O3) in pharmaceutical formulations using electrospray ionization mass spectrometry (ESI‐MS) following iron complexation with 4‐(2‐pyridylazo)resorcinol (PAR) was evaluated. Complexation of FeIII with PAR was found to produce an intense mass spectral signal at low pH compared to the free ligand. Using the selected‐ion‐monitoring mode of a triple‐quadrupole mass spectrometer, the signal at m/z 484 arising from the singly charged [FeIII(PAR)2]+ complex gave a limit of detection of ∼2 µM for total iron. The linear range of the calibration curve was found to be 2–43 µM total iron. Trace iron interference was decreased to submicromolar levels by performing an optimized labware cleaning protocol and instrument replumbing using Polyetheretherketone (PEEK) tubing. The validation parameters of this ESI‐MS total iron analysis (specificity, linearity, precision, accuracy, robustness and stability) are within the acceptance criteria listed in the validation guidelines developed by the Food and Drug Administration for industry. Recovery of 93% of the added iron indicated a satisfactory extraction procedure for tablets containing Fe2O3 pigment. There was no statistical difference between the results obtained by ESI‐MS and the common elemental method, inductively coupled plasma‐optical emission spectroscopy. Since the proposed ESI‐MS method can be performed on a mass spectrometer equipped with an ESI source, which is standard instrumentation in the pharmaceutical industry, the method validated here provides an alternate method for metal ion analysis by ESI‐MS. Copyright © 2011 John Wiley & Sons, Ltd.
Electrothermal model of a power LED for SPICE
Authors: Górecki Krzysztof 
Published: April 2011

SUMMARYIn this paper an electrothermal model of the power LED dedicated for SPICE is proposed. In this model electrical, thermal and optical properties of the considered device are taken into account. The description of the model and some results of the experimental verification of this model are presented for two types of power LEDS: LXHL‐BW03 and LXHL‐LW3C produced by Lumileds. A good agreement between the results of measurements and calculations is obtained. Copyright © 2011 John Wiley & Sons, Ltd.
Modelling and fabrication of optimum structure of novel interdigital sensors for food inspection
Authors: Mohd Syaifudin A. R. , Mukhopadhyay S. C. , Yu P. L. 
Published: April 2011

SUMMARYModelling of an interdigital sensor‐based sensing system for the detection of dangerous contaminated marine biotoxin in seafood has been carried out. Three interdigital sensors having new electrode configurations have been analysed using COMSOL Multiphysics. All sensors were designed to have an equal number of electrodes with the same sensing area. Based on the maximum sensitivity, the best electrode configuration has been chosen. Experiments on raw seafood contaminated with domoic acid have been conducted using the new fabricated sensor and very good results were obtained. Copyright © 2011 John Wiley & Sons, Ltd.
An artificial tendon to connect the quadriceps muscle to the Tibia
Authors: Melvin Alan , Litsky Alan , Mayerson Joel , Stringer Keith , Melvin David , Juncosa‐Melvin Natalia 
Published: April 2011

AbstractNo permanent, reliable artificial tendon exists clinically. Our group developed the OrthoCoupler™ device as a versatile connector, fixed at one end to a muscle, and adaptable at the other end to inert implants such as prosthetic bones or to bone anchors. The objective of this study was to evaluate four configurations of the device to replace the extensor mechanism of the knee in goats. Within muscle, the four groups had: (A) needle‐drawn uncoated bundles, (B) needle‐drawn coated bundles, (C) barbed uncoated bundles, and (D) barbed coated bundles. The quadriceps tendon, patella, and patellar tendon were removed from the right hind limb in 24 goats. The four groups (n = 6 for each) were randomly assigned to connect the quadriceps muscle to the tibia (with a bone plate). Specimens were collected from each operated leg and contralateral unoperated controls both for mechanical testing and histology at 90 days post‐surgery. In strength testing, maximum forces in the operated leg (vs. unoperated control) were 1,288 ± 123 N (vs. 1,387 ± 118 N) for group A, 1,323 ± 144 N (vs. 1,396 ± 779 N) for group B, 930 ± 125 N (vs. 1,337 ± 126 N) for group C, and 968 ± 109 N (vs. 1,528 ± 146 N) for group D (mean ± SEM). The strengths of the OrthoCoupler™ legs in the needled device groups were equivalent to unoperated controls (p = 0.6), while both barbed device groups had maximum forces significantly lower than their controls (p = 0.001). We believe this technology will yield improved procedures for clinical challenges in orthopaedic oncology, revision arthroplasty, tendon transfer, and tendon injury reconstruction. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1775–1782, 2011
Carpal tunnel and transverse carpal ligament stiffness with changes in wrist posture and indenter size
Authors: Holmes Michael W. R. , Howarth Samuel J. , Callaghan Jack P. , Keir Peter J. 
Published: April 2011

AbstractThis study investigated the effects of loading and posture on mechanical properties of the transverse carpal ligament (TCL). Ten fresh‐frozen cadaver arms were dissected to expose the TCL and positioned in the load frame of a servo‐hydraulic testing machine, equipped with a load cell and custom made indenters. Four cylindrical indenters (5, 10, 20, and 35 mm) loaded the TCL in three wrist postures (30° extension, neutral and 30° flexion). Three loading cycles with a peak force of 50 N were applied at 5 N/s for each condition. The flexed wrist posture had significantly greater TCL stiffness (40.0 ± 3.3 N/mm) than the neutral (35.9 ± 3.5 N/mm, p = 0.045) and extended postures (34.9 ± 2.8 N/mm, p = 0.025). TCL stiffness using the 10 and 20 mm indenters was larger than the 5 mm indenter. Stiffness was greatest with the 20 mm indenter, which had the greatest indenter contact area on the TCL. The 35 mm indenter covered the carpal bones, compressed the carpal tunnel and produced the lowest stiffness. The complexity of the TCL makes it an important part of the carpal tunnel and the mechanical properties found are essential to understanding mechanisms of carpal tunnel syndrome. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1682–1687, 2011
Capsule preservation improves short‐term outcome of hydraulic distension in painful stiff shoulder
Authors: Kim Keewon , Lee Kyu Jin , Kim Hee Chan , Lee Kun‐Jai , Kim Don‐Kyu , Chung Sun G. 
Published: April 2011

AbstractThe effect of intraarticular hydraulic distension (IHD) for a painful stiff shoulder (or adhesive capsulitis) has been affirmed, but whether rupturing the joint capsule during this process is beneficial remains controversial. By monitoring real‐time pressure–volume (PV) profiles during IHD, we could infuse the largest possible volume without rupturing the capsule. Using the novel technique, we compared the short‐term effects of IHD when the capsule was preserved versus when it was ruptured. Fifty‐four patients with a painful stiff shoulder underwent IHDs intended to preserve or rupture the capsule and then classified into capsule‐ruptured (n = 26) and capsule‐preserved (n = 20) groups, based on the obtained PV profiles. Their profiles were triphasic or biphasic; eight with flat profiles were excluded from the comparison. Clinical outcomes were evaluated at 3‐day and 1‐month follow‐ups, in terms of pain and range of motion (ROM). Although both groups showed significant increase in ROM and decrease in pain after IHD, the improvements were greater in the capsule‐preserved group than in the ruptured group at both follow‐up times, and in triphasic and biphasic cases. In conclusion, the therapeutic effects of IHD in short‐term follow‐ups were enhanced by preserving the capsule. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1688–1694, 2011
Determinants of outcomes in pancreatic surgery and use of hospital resources
Authors: Gupta Prateek K. , Turaga Kiran K. , Miller Weldon J. , Loggie Brian W. , Foster Jason M. 
Published: April 2011

AbstractBackground and ObjectivesOutcomes for patients undergoing major pancreatic surgery have improved, but a subset of patients that significantly utilize more resources exists. Variables that can lead to an increase in resource utilization in patients undergoing pancreatic surgery were identified.MethodsPatients undergoing pancreatic surgery for neoplasms were identified from the NSQIP database (2006–2008). Indices associated with increased resource utilization that we included were operative time (OT), length of stay (LOS), intraoperative RBC transfusion, return to operating room, and occurrence of postoperative complications. Analysis of covariance and multivariable logistic regression were performed.ResultsThe 4,306 included patients had a median age of 66 years and 50.3% were males. The 30‐day morbidity and mortality were 29.3% and 3.2%, respectively. Median OT was 362 min and median LOS was 10 days. Malignancy, neoadjuvant radiation, and medical co‐morbidities were associated with increased OT (P < 0.0001 for all). Declining preoperative functional status was the most important predictor of LOS (P < 0.0001). Age, male gender, hypertension, severe COPD, and higher BMI were significantly associated with postoperative complications (P < 0.050 for all).ConclusionsMorbidity after pancreatic surgery remains high. Age, obesity, performance status, medical co‐morbidities, and neoadjuvant radiation affect outcomes and may lead to increased use of hospital resources. J. Surg. Oncol. 2011; 104:634–640. © 2011 Wiley Periodicals, Inc.
Preoperative portal vein embolization (PVE) for patients with hepatocellular carcinoma can improve resectability and may improve disease‐free survival
Authors: Okabe Hirohisa , Beppu Toru , Ishiko Takatoshi , Masuda Toshiro , Hayashi Hiromitsu , Otao Ryu , Hasita Horlad , Okabe Kazutoshi , Sugiyama Shinichi , Baba Hideo 
Published: April 2011

AbstractBackgroundThe aim of this study is to identify the efficacy of portal vein embolization (PVE) before right hepatectomy in patients with hepatocellular carcinoma (HCC) with regard to hepatic function, surgical stress, and survival benefit.MethodsFifty‐five patients with HCC underwent right hepatectomy between 1999 and 2009. Preoperative PVE was performed in 19 patients (PVE group) and was not applied in 36 patients (non‐PVE group). Changes in liver function and volume were investigated in PVE group. Short and long clinical outcomes after the surgeries were compared between the two groups.ResultsThe percentage of future liver remnant (%FLR) before PVE was significantly lower (37.8%) in PVE group than in non‐PVE group (58.1%) but increased remarkably after PVE (from 37.8% to 55.0%, P < 0.0001). Cumulative disease‐free survival and overall survival rates in PVE group were significantly superior to those in non‐PVE group (P = 0.010 and 0.049, respectively). Although surgical stress estimated by E‐PASS scores and CRP value was not different between the groups, the postoperative value of PT on postoperative day 3 in PVE group was significantly better than in non‐PVE group.ConclusionsPreoperative PVE improves resectability and may improve disease‐free survival for patients with HCC requiring right hepatectomy. J. Surg. Oncol. 2011; 104:641–646. © 2011 Wiley Periodicals, Inc.