bluuebunny/crossref_metadata_2025 huggingface dataset:
Doped Titanium Dioxide Films Prepared by Pulsed Laser Deposition Method
Authors: Hu Juguang , Tang Huabin , Lin Xiaodong , Luo Zhongkuan , Cao Huiqun , Li Qiwen , Liu Yi , Long Jinghua , Wang Pei
Published: June 2012

TiO2was intensively researched especially for photocatalystic applications. The nitrogen-doped TiO2films prepared by pulsed laser deposition (PLD) method were reviewed, and some recent new experimental results were also presented in this paper. A new optical transmission method for evaluating the photocatalystic activity was presented. The main results are (1) PLD method is versatile for preparing oxide material or complex component films with excellent controllability and high reproducibility. (2) Anatase nitrogen-doped TiO2films were prepared at room temperature, 200°C, and 400°C by PLD method using novel ceramic target of mixture of TiN and TiO2. UV/Vis spectra, AFM, Raman spectra, and photocatalystic activity for decomposition of methyl orange (MO) tests showed that visible light response was improved at higher temperature. (3) The automatic, continuous optical transmission autorecorder method is suitable for detecting the photodecomposition dynamic process of organic compound.
Best Periodic Proximity Points for Cyclic Weaker Meir‐Keeler Contractions
Authors: Chen Chiming , Lin Chingju
Published: June 2012

The purpose of this paper is to present the existence of the best period proximity point for cyclic weaker Meir‐Keeler contractions and asymptotic cyclic weaker Meir‐Keeler contractions in metric spaces.
Identification of Risk Factors for Vascular Thrombosis May Reduce Early Renal Graft Loss: A Review of Recent Literature
Authors: Keller Anna Krarup , Jorgensen Troels Munch , Jespersen Bente
Published: June 2012

Renal graft survival has improved over the past years, mainly owing to better immunosuppression. Vascular thrombosis, though rare, therefore accounts for up to one third of early graft loss. We assess current literature on transplantation, identify thrombosis risk factors, and discuss means of avoiding thrombotic events and saving thrombosed grafts. The incidence of arterial thrombosis was reported to 0.2–7.5% and venous thrombosis 0.1–8.2%, with the highest incidence among children and infants, and the lowest in living donor reports. The most significant risk factors for developing thrombosis were donor-age below 6 or above 60 years, or recipient-age below 5-6 years, per- or postoperative hemodynamic instability, peritoneal dialysis, diabetic nephropathy, a history of thrombosis, deceased donor, or >24 hours cold ischemia. Multiple arteries were not a risk factor, and a right kidney graft was most often reported not to be. Given the thrombosed kidney graft is diagnosed in time, salvage is possible by urgent reoperation and thrombectomy. Despite meticulous attentions to reduce thrombotic risk factors, thrombosis cannot be entirely prevented and means to an early detection of this complication is desirable in order to save the kidneys through prompt reoperation. Microdialysis may be a new tool for this.
Asymptotic Stability of Differential Equations with Infinite Delay
Authors: Piriadarshani D. , Sengadir T.
Published: June 2012

A theorem on asymptotic stability is obtained for a differential equation with an infinite delay in a function space which is suitable for the numerical computation of the solution to the infinite delay equation.
A New Multipath Mitigation Method for GNSS Receivers Based on an Antenna Array
Authors: Rougerie Sébastien , Carrié Guillaume , Vincent François , Ries Lionel , Monnerat Michel
Published: June 2012

The well-known Space-Alternating Generalized Expectation Maximisation (SAGE) algorithm has been recently considered for multipath mitigation in Global Navigation Satellite System (GNSS) receivers. However, the implementation of SAGE in a GNSS receiver is a challenging issue due to the numerous number or parameters to be estimated and the important size of the data to be processed. A new implementation of the SAGE algorithm is proposed in this paper in order to reach the same efficiency with a reduced complexity. This paper focuses on the trade-off between complexity and performance thanks to the Cramer Rao bound derivation. Moreover, this paper shows how the proposed algorithm can be integrated with a classical GNSS tracking loop. This solution is thus a very promising approach for multipath mitigation.
Maxillary Tuberosity Reconstruction with Transport Distraction Osteogenesis
Authors: Ugurlu F. , Basel B. , Sener B. Cem , Sertgöz A.
Published: June 2012

Severe bone loss due to pathology in the maxillary tuberosity region is a challenging problem both surgically and prosthetically. Large bone grafts have a poor survival rate due to the delicate bony architecture in this area and presence of the maxillary sinus. Our case presentation describes a new technique for reconstructing severe bony defect in the maxillary tuberosity with horizontal distraction osteogenesis in a 45-year-old man. A cm cyst was discovered in the left maxillary molar region and enucleated. Three months postoperatively, the area had a severe bone defect extending to the zygomatic buttress superiorly and hamular notch posteriorly. Three months later, a bone segment including the right upper second premolar was osteotomised and distracted horizontally. The bone segment was distracted 15 mm distally. After consolidation, implants were placed when the distractor was removed. A fixed denture was loaded over the implants after 3 months. Complete alveolar bone loss extending to the cranial base can be reconstructed with transport distraction osteogenesis. Distalisation of the alveolar bone segment adjacent to the bony defect is an easy method for reconstructing such severe defects.
Broadband Transmission and Statistical Performance Properties of Overhead High-Voltage Transmission Networks
Authors: Lazaropoulos Athanasios G.
Published: June 2012

This paper considers broadband signal transmission and statistical performance properties of high-voltage/broadband over power lines (HV/BPL) channels associated with overhead power transmission. The overhead HV/BPL transmission channel is investigated with regard to its spectral behavior, its end-to-end signal attenuation, and its statistical performance metrics. It is found that the above features depend critically on the frequency, the overhead HV power grid type (150 kV, 275 kV, or 400 kV and single- or double-circuit), the coupling scheme applied, the physical properties of the cables used, the MTL configuration, and the type of branches existing along the end-to-end BPL signal propagation. The contribution of this paper is threefold. First, the significant broadband transmission potential of overhead HV lines is revealed. The results demonstrate that, regardless of overhead HV power grid type, the overhead HV grid is a potentially excellent communications medium, offering low-loss characteristics, flat-fading features, and low multipath dispersion over a 25 km repeater span well beyond 100 MHz. Second, regarding the statistical properties of various overhead HV/BPL transmission channels, two fundamental correlations of several wireline systems, for example, coaxial cables and xDSL, are also validated in the case of overhead HV/BPL transmission channels, namely, (i) end-to-end channel attenuation in relation with root-mean-square delay spread (RMS-DS) and (ii) coherence bandwidth (CB) in relation with RMS-DS. Third, fitting the numerical results and other field trial measurements, two regression distributions suitable for each fundamental correlation are proposed.
Atypical Omenn Syndrome due to Adenosine Deaminase Deficiency
Authors: Joshi Avni Y. , Ham Erin K. , Shah Neel B. , Dong Xiangyang , Khan Shakila P. , Abraham Roshini S.
Published: June 2012

We present here a novel case of an atypical Omenn syndrome (OS) phenotype due to mutations in theADAgene encoding adenosine deaminase. This case is noteworthy for a significant increase in circulating CD56brightCD16- cytokine-producing NK cells after treatment with steroids for skin rash.
Noninvasive Evaluation of Injectable Chitosan/Nano‐Hydroxyapatite/Collagen Scaffold via Ultrasound
Authors: Chen Yan , Li Songjian , Li Xiaoming , Zhang Yichen , Huang Zhi , Feng Qingling , Zhou Zhilai , Lin Bomiao , Yu Bo
Published: June 2012

To meet the challenges of designing an in situ forming scaffold and regenerating bone with complex three‐dimensional (3D) structures, an in situ forming hydrogel scaffold based on nano‐hydroxyapatite (nHA), collagen (Col), and chitosan (CS) was synthesized. Currently, only a limited number of techniques are available to mediate and visualize the injection process of the injectable biomaterials directly and noninvasively. In this study, the potential of ultrasound for the quantitative in vivo evaluation of tissue development in CS/nHAC scaffold was evaluated. The CS/nHAC scaffold was injected into rat subcutaneous tissue and evaluated for 28 days. Quantitative measurements of the gray‐scale value, volume, and blood flow of the scaffold were evaluated using diagnostic technique. This study demonstrates that ultrasound can be used to noninvasively and nondestructively monitor and evaluate the in vivo characteristics of injectable bone scaffold. In comparison to the CS, the CS/nHAC scaffold showed a greater stiffness, less degradation rate, and better blood supply in the in vivo evaluation. In conclusion, the diagnostic ultrasound method is a good tool to evaluate the in vivo formation of injectable bone scaffolds and facilitates the broad use to monitor tissue development and remodeling in bone tissue engineering.
Primary Hyperparathyroidism: 11-Year Experience in a Single Institute in Thailand
Authors: Prasarttong-Osoth Poramaporn , Wathanaoran Pakpong , Imruetaicharoenchoke Waraporn , Rojananin Supakorn
Published: June 2012

Primary hyperparathyroidism (PHPT) is not an uncommon disease in the western countries. In Thailand, on the contrary, PHPT was a rare condition with various clinical presentations. All 45 PHPT patients who underwent parathyroidectomy at the Department of Surgery, Siriraj Hospital during January 1997 and December 2007 were retrospectively reviewed. Demographic data, clinical presentation, localizations imaging, operative procedures, findings, complications, and pathological reports were analyzed. Median age was 49 years (range 15–89 years) with female: male ratio of 3 : 1. Only one patient (2.2%) was asymptomatic PHPT. Of all symptomatic cases, 30 (66.7%) had skeletal symptoms, 7 (15.6%) had renal impairment, and 39 (86.7%) had mixed symptoms. 42 patients (93.3%) had parathyroid scan and all had bilateral exploration of the neck. Postoperative hungry bone syndrome was noted in 10 patients (22%). On followup, skeletal and neuropsychiatric symptoms were improved but the renal impairment was remained. Thessmall number of asymptomatic PHPT in our study may refer to large number of underdiagnosed PHPT in general population. The guideline for screening serum calcium for diagnosis of PHPT in Thai populations will improve the long-term consequence of the disease but will need further information to identify the target group.
Identification of a Molecular Signature Underlying Inhibition of Mammary Carcinoma Growth by Dietary N-3 Fatty Acids
Authors: Jiang Weiqin , Zhu Zongjian , McGinley John N. , El Bayoumy Karam , Manni Andrea , Thompson Henry J.
Published: June 2012

An increased ratio of dietary n-3 relative to n-6 fatty acids has been shown to inhibit the development of mammary cancer in animal models. However, the molecular mechanisms by which n-3 fatty acids affect tumor growth remain unknown. Here, we investigated the effects of varying dietary ratios of n-3:n-6 fatty acids on cell signaling in a rat model of chemically induced mammary carcinoma. Cell proliferation was reduced by 60% in carcinomas from the high n-3:n-6 treatment group compared with the low n-3:n-6 treatment group. These changes were associated with decreased cyclin-D1 and phospho-retinoblastoma protein expression and increased levels of cyclin-dependent kinase inhibitors, CIP1 (p21) and KIP1 (p27). In addition, the apoptotic index was increased in carcinomas from the high n-3:n-6 group and was associated with elevated apoptotic protease-activating factor 1 and a higher ratio of Bax/Bcl-2. Interestingly, changes in protein expression were consistent with reduced inflammation and suppressed mTOR activity, and the molecular signature associated with high n-3:n-6 treatment revealed changes in PPARγ activation and suppression of lipid synthesis. Together, our findings indicate that the molecular effects of high dietary n-3 to n-6 ratios are heterogeneous in nature but point to consistent changes in lipid metabolism pathways, which may serve as potential therapeutic targets for cancer prevention and control. This study identifies the pathways modulated by dietary fatty acid ratios in a rat model of breast cancer, with implications for cancer prevention. Cancer Res; 72(15); 3795–806. ©2012 AACR.
Complete Longitudinal Analyses of the Randomized, Placebo-Controlled, Phase III Trial of Sunitinib in Patients with Gastrointestinal Stromal Tumor following Imatinib Failure
Authors: Demetri George D. , Garrett Christopher R. , Schöffski Patrick , Shah Manisha H. , Verweij Jaap , Leyvraz Serge , Hurwitz Herbert I. , Pousa Antonio Lopez , Le Cesne Axel , Goldstein David , Paz-Ares Luis , Blay Jean-Yves , McArthur Grant A. , Xu Qiang (Casey) , Huang Xin , Harmon Charles S. , Tassell Vanessa , Cohen Darrel P. , Casali Paolo G.
Published: June 2012

Purpose: To analyze final long-term survival and clinical outcomes from the randomized phase III study of sunitinib in gastrointestinal stromal tumor patients after imatinib failure; to assess correlative angiogenesis biomarkers with patient outcomes.

Experimental Design: Blinded sunitinib or placebo was given daily on a 4-week-on/2-week-off treatment schedule. Placebo-assigned patients could cross over to sunitinib at disease progression/study unblinding. Overall survival (OS) was analyzed using conventional statistical methods and the rank-preserving structural failure time (RPSFT) method to explore cross-over impact. Circulating levels of angiogenesis biomarkers were analyzed.

Results: In total, 243 patients were randomized to receive sunitinib and 118 to placebo, 103 of whom crossed over to open-label sunitinib. Conventional statistical analysis showed that OS converged in the sunitinib and placebo arms (median 72.7 vs. 64.9 weeks; HR, 0.876; P = 0.306) as expected, given the cross-over design. RPSFT analysis estimated median OS for placebo of 39.0 weeks (HR, 0.505, 95% CI, 0.262–1.134; P = 0.306). No new safety concerns emerged with extended sunitinib treatment. No consistent associations were found between the pharmacodynamics of angiogenesis-related plasma proteins during sunitinib treatment and clinical outcome.

Conclusions: The cross-over design provided evidence of sunitinib clinical benefit based on prolonged time to tumor progression during the double-blind phase of this trial. As expected, following cross-over, there was no statistical difference in OS. RPSFT analysis modeled the absence of cross-over, estimating a substantial sunitinib OS benefit relative to placebo. Long-term sunitinib treatment was tolerated without new adverse events. Clin Cancer Res; 18(11); 3170–9. ©2012 AACR.
The Checkpoint Kinase Inhibitor AZD7762 Potentiates Chemotherapy-Induced Apoptosis of p53-Mutated Multiple Myeloma Cells
Authors: Landau Heather J. , McNeely Samuel C. , Nair Jayasree S. , Comenzo Raymond L. , Asai Takashi , Friedman Hillel , Jhanwar Suresh C. , Nimer Stephen D. , Schwartz Gary K.
Published: June 2012

DNA cross-linking agents are frequently used in the treatment of multiple myeloma–generating lesions, which activate checkpoint kinase 1 (Chk1), a critical transducer of the DNA damage response. Chk1 activation promotes cell survival by regulating cell-cycle arrest and DNA repair following genotoxic stress. The ability of AZD7762, an ATP-competitive Chk1/2 inhibitor to increase the efficacy of the DNA-damaging agents bendamustine, melphalan, and doxorubicin was examined using four human myeloma cell lines, KMS-12-BM, KMS-12-PE, RPMI-8226, and U266B1. The in vitro activity of AZD7762 as monotherapy and combined with alkylating agents and the “novel” drug bortezomib was evaluated by studying its effects on cytotoxicity, signaling, and apoptotic pathways. The Chk1/2 inhibitor AZD7762 potentiated the antiproliferative effects of bendamustine, melphalan, and doxorubicin but not bortezomib in multiple myeloma cell lines that were p53-deficient. Increased γH2AX staining in cells treated with bendamustine or melphalan plus AZD7762 indicates a greater degree of DNA damage with combined therapy. Abrogation of the G2–M checkpoint by AZD7762 resulted in mitotic catastrophe with ensuing apoptosis evidenced by PARP and caspase-3 cleavage. In summary, the cytotoxic effects of bendamustine, melphalan and doxorubicin on p53-deficient multiple myeloma cell lines were enhanced by the coadministration of AZD7762. These data provide a rationale for testing these combinations in patients with relapsed and/or refractory multiple myeloma. Mol Cancer Ther; 11(8); 1781–8. ©2012 AACR.
Characterization of the Mechanism of Action of the Pan Class I PI3K Inhibitor NVP-BKM120 across a Broad Range of Concentrations
Authors: Brachmann Saskia M. , Kleylein-Sohn Julia , Gaulis Swann , Kauffmann Audrey , Blommers Marcel J.J. , Kazic-Legueux Malika , Laborde Laurent , Hattenberger Marc , Stauffer Fabian , Vaxelaire Juliane , Romanet Vincent , Henry Chrystèle , Murakami Masato , Guthy Daniel Alexander , Sterker Dario , Bergling Sebastian , Wilson Christopher , Brümmendorf Thomas , Fritsch Christine , Garcia-Echeverria Carlos , Sellers William R. , Hofmann Francesco , Maira Sauveur-Michel
Published: June 2012

The pan-phosphoinositide 3-kinase (PI3K) inhibitor BKM120 was found, at high concentrations, to cause cell death in various cellular systems, irrespective of their level of PI3K addiction. Transcriptional and biochemical profiling studies were used to identify the origin of these unexpected and apparently PI3K-independent effects. At 5- to 10-fold, the concentration needed to half-maximally inhibit PI3K signaling. BKM120 treatment caused changes in expression of mitotic genes and the induction of a robust G2–M arrest. Tubulin polymerization assays and nuclear magnetic resonance-binding studies revealed that BKM120 inhibited microtubule dynamics upon direct binding to tubulin. To assess the contribution of this off-target activity vis-à-vis the antitumor activity of BKM120 in PI3K-dependent tumors, we used a mechanistic PI3K-α–dependent model. We observed that, in vivo, daily treatment of mice with doses of BKM120 up to 40 mg/kg led to tumor regressions with no increase in the mitotic index. Thus, strong antitumor activity can be achieved in PI3K-dependent models at exposures that are below those necessary to engage the off-target activity. In comparison, the clinical data indicate that it is unlikely that BKM120 will achieve exposures sufficient to significantly engage the off-target activity at tolerated doses and schedules. However, in preclinical settings, the consequences of the off-target activity start to manifest themselves at concentrations above 1 μmol/L in vitro and doses above 50 mg/kg in efficacy studies using subcutaneous tumor–bearing mice. Hence, careful concentration and dose range selection is required to ensure that any observation can be correctly attributed to BKM120 inhibition of PI3K. Mol Cancer Ther; 11(8); 1747–57. ©2012 AACR.
Protein Kinase C Inhibitor AEB071 Targets Ocular Melanoma Harboring GNAQ Mutations via Effects on the PKC/Erk1/2 and PKC/NF-κB Pathways
Authors: Wu Xinqi , Li Jingjing , Zhu Meijun , Fletcher Jonathan A. , Hodi F. Stephen
Published: June 2012

Somatic GNAQ mutations at codon 209 have been identified in approximately 50% of uveal melanomas and have been reported to be oncogenic through activating PLCβ/PKC/Erk1/2 pathways. We hypothesized that protein kinase C (PKC) may provide new opportunities for therapeutic targeting of uveal melanoma carrying GNAQ mutations. To test this hypothesis, uveal melanoma cells harboring wild-type or mutant GNAQ were treated with the PKC inhibitor AEB071 (sotrastaurin) or infected with lentivirus-expressing short hairpin RNAs (shRNA) targeting PKC isoforms. Notably, AEB071 at low micromolar concentrations significantly inhibited the growth of uveal melanoma cells harboring GNAQ mutations through induction of G1 arrest and apoptosis. However, AEB071 had little effect on uveal melanoma cells carrying wild-type GNAQ. AEB071-mediated cell inhibition in the GNAQ-mutated uveal melanoma was accompanied by inhibition of extracellular signal–regulated kinase (Erk)1/2 phosphorylation, NF-κB, decreased expression of cyclin D1, survivin, Bcl-xL, and XIAP, and increased expression of cyclin-dependent kinase inhibitor p27Kip1. AEB071 suppressed the expression of PKC α, β, δ, ϵ, and θ in GNAQ-mutated uveal melanoma cells. Our findings from shRNA-mediated knockdown studies revealed that these PKC isoforms are functionally important for uveal melanoma cells harboring GNAQ mutations. Furthermore, inhibitors of Erk1/2 and NF-κB pathways reduced viability of uveal melanoma cells. Together, our findings show that AEB071 exerts antitumor action on uveal melanoma cells carrying GNAQ mutations via targeting PKC/Erk1/2 and PKC/NF-κB pathways. Targeted PKC inhibition with drugs such as AEB071 offers novel therapeutic potential for uveal melanoma harboring GNAQ mutations. Mol Cancer Ther; 11(9); 1905–14. ©2012 AACR.
Oxidative Stress Induced by Curcumin Promotes the Death of Cutaneous T-cell Lymphoma (HuT-78) by Disrupting the Function of Several Molecular Targets
Authors: Khan Mohammad Aslam , Gahlot Satindra , Majumdar Sekhar
Published: June 2012

Curcumin is known to exert its anticancer effect either by scavenging or by generating reactive oxygen species (ROS). In this study, we report that curcumin-mediated rapid generation of ROS induces apoptosis by modulating different cell survival and cell death pathways in HuT-78 cells. Curcumin induces the activation of caspase-8, -2, and -9, alteration of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-3 and concomitant PARP cleavage, but the addition of caspase inhibitors only partially blocked the curcumin-mediated apoptosis. Curcumin also downregulates the expression of antiapoptotic proteins c-FLIP, Bcl-xL, cellular inhibitor of apoptosis protein, and X-linked IAP in a ROS-dependent manner. Curcumin disrupts the integrity of IKK and beclin-1 by degrading Hsp90. Degradation of IKK leads to the inhibition of constitutive NF-κB. Degradation of beclin-1 by curcumin leads to the accumulation of autophagy-specific marker, microtubule-associated protein-I light chain 3 (LC3), LC3-I. Our findings indicate that HuT-78 cells are vulnerable to oxidative stress induced by curcumin and as a result eventually undergo cell death. Mol Cancer Ther; 11(9); 1873–83. ©2012 AACR.
Evaluation of Conventional Doppler Fetal Cardiac Function Parameters: E/A Ratios, Outflow Tracts, and Myocardial Performance Index
Authors: Hernandez-Andrade Edgar , Benavides-Serralde Jesus Andres , Cruz-Martinez Rogelio , Welsh Alec , Mancilla-Ramirez Javier
Published: June 2012

Structural evaluation of the fetal heart is well established. Functional evaluation using pulsed-wave Doppler may also be performed. E/A ratios express the relationship between the maximal velocities of the E and A waveforms of ventricular filling. In normal fetuses, E/A ratios are usually <1 but show a constant increment during gestation, mainly related to the increment of the E wave. In intrauterine growth restriction (IUGR) fetuses, E/A ratios are lower compared to values in normally grown fetuses at the same gestational age. Cardiac outflows provide information on the time-velocity integral that, combined with the vessel area, allows calculation of the left and right cardiac outputs. In normal fetuses there is a predominance of the right ventricle (55–60%) in contributing to the combined cardiac output. In IUGR fetuses this predominance shifts to the left ventricle in order to increase the flow to the upper part of the fetal body and brain. The myocardial performance index (MPI) also provides information on systolic and diastolic cardiac function. The MPI is an early and consistent marker of cardiac dysfunction which becomes altered in early stages of chronic hypoxia or in cases with cardiac overload such as in twin-to-twin transfusion syndrome.
Hepatitis E Virus Infection Causing Isolated Fetal Ascites: A Case Report
Authors: Pradhan Mandakini , Anand Bhavna , Singh Asha
Published: June 2012

Maternal hepatitis infection, excepting hepatitis E, causing isolated fetal ascites with variable outcome has been reported previously. We present a case of maternal hepatitis E virus (HEV) infection causing isolated fetal ascites which resolved spontaneously during pregnancy and resulted in a term live-born baby with anti-HEV seropositivity. A 39-year-old primigravida woman was diagnosed with acute HEV infection at 15 weeks of gestation. Ultrasound at 19 weeks showed significant fetal ascites with abdominal calcifications. Fetal karyotype did not show any abnormality. Cord blood was positive for anti-HEV IgM and negative for other intrauterine infections. Ultrasound at 25 weeks showed partial resolution of fetal ascites with complete resolution at 30 weeks. She delivered a healthy baby at 38 completed weeks, with normal liver enzymes at birth and 1-month follow-up.
Contact Photoallergy to Isothipendyl Chlorhydrate
Authors: Bibas N. , Sartor V. , Bulai Livideanu C. , Bagheri H. , Nougué J. , Giordano-Labadie F. , Maza A. , Paul C. , Chouini-Lalanne N. , Marguery M.-C.
Published: June 2012

Isothipendyl chlorhydrate is an azaphenothiazine, an active ingredient of an antipruriginous gel, Apaisyl gel® (Merck Médication Familiale, Dijon, France). Although Apaisyl gel is registered and used worldwide, we present the first case of contact photoallergy to isothipendyl chlorhydrate to our knowledge. The diagnosis suspected on the basis of a positive UVA photopatch test to chlorpromazine was confirmed by a strongly positive UVA Apaisyl gel photopatch test and our photophysical studies. This case confirms the need to keep the phenothiazines in the photopatch test standard series as a diagnostic marker of phenothiazine photoallergy.
Single Umbilical Artery: Does Side Matter?
Authors: Santillan Mark , Santillan Donna , Fleener Diedre , Stegmann Barbara , Zamba Gideon , Hunter Stephen , Yankowitz Jerome
Published: June 2012

Introduction: The aim of this study was to determine if laterality of an absent umbilical artery (AUA) is associated with specific sonographic findings, chromosomal defects or postpartum birth defects. Materials and Methods: In this retrospective cohort study, ultrasound reports and medical records of patients who received an obstetric ultrasound at the University of Iowa Hospitals and Clinics with an identified laterality of the AUA from 1989 to 2007 (n = 405) were reviewed. Rates of sonographic abnormalities between fetuses with a right versus left AUA were compared using Fisher’s exact test. Adjustments for confounding were made using logistic regression modeling. The significance level was set at 0.05. Results: Right AUAs on ultrasound demonstrate higher unadjusted rates of ultrasound abnormalities with a higher percentage of fetuses with >1 additional abnormality (51.1 vs. 37.0%; p = 0.0043). The left AUA group had a significantly higher percentage of isolated AUA (63.0 vs. 48.8%; p = 0.004). In a multivariate analysis, a sonographic right AUA was significantly associated with gastrointestinal (GI) and genitourinary (GU) abnormalities. No other ultrasonographic and umbilical artery Doppler abnormalities, chromosomal defects or postpartum birth defects were significantly associated with a specific laterality of the AUA. Discussion: Our study identified a significant association between a right AUA and concomitant fetal GI and GU abnormalities. Contrary to previous reports, we conclude that laterality of the AUA may prove to be an easily identified early marker of fetal abnormalities.
Challenges for Synthesising Data in a Network of Registries for Systemic Psoriasis Therapies
Authors: Ormerod A.D. , Augustin M. , Baker C. , Chosidow O. , Cohen A.D. , Dam T.N. , Garcia-Doval I. , Lecluse L.L. , Schmitt-Egenolf M. , Spuls P.I. , Watson K.D. , Naldi L.
Published: June 2012

Background: Large disease registries are the preferred method to assess long-term treatment safety. If psoriasis registries collaborate in a network, their power to assess safety is increased. Objective: To identify heterogeneity in psoriasis registries and methodological challenges for synthesising the data they provide. Methods: We surveyed the registries in PSONET and identified and addressed the challenges to collaborative analysis for the network in several round table meetings. Results: Eight out of 10 registries had a prospective comparator cohort with similar disease characteristics but not on biologics. Registries differed in the coding and validation or follow-up of adverse events and in the way they sampled their population. Fifteen challenges to registries collaborating were identified in the areas of operational governance, structural conduct, bias and analysis. Conclusions: Participation in PSONET, a network of psoriasis registries, helps identify and solve common issues, enhancing the individual registries, and provides larger sets of more powerful safety data in a diverse population. Challenges to interpreting data collectively include heterogeneity in sampling, variable penetration of biologics and compatibility of different datasets.
Herpes Zoster in Patients Treated with Biologicals
Authors: Failla V. , Jacques J. , Castronovo C. , Nikkels A.F.
Published: June 2012

Background: The incidence and severity of herpes zoster (HZ) appear increased in patients receiving tumor necrosis factor-α antagonists. Objective: To study the incidence and clinical features of HZ in 1,220 patients (4,206 patient-years) receiving either adalimumab, etanercept, infliximab, rituximab or ustekinumab. Results: Twenty-two HZ cases were identified [1.26% of total cohort; adalimumab: 11/1,546 patient-years, incidence rate (IR) 7.1; etanercept: 4/789 patient-years, IR 5.1; rituximab: 1/168 patient-years, IR 5.2; ustekinumab: 2/37 patient-years, IR 53.5; infliximab: 4/1,666 patient-years, IR 2.4]. The time to event varied widely (1.5– 108 months). Extensive HZ was reported in 45 and 32% of the cases, respectively. Persistent postzoster neuralgia (PHN; >6 months) was observed in 5/20 patients. Conclusions: The HZ incidence was 2.1-fold higher among patients over 60 years, compared with a reference population, although not statistically significant. Severe, multidermatomal HZ and persistent PHN were common.
Five Cases of Contact Dermatitis to a Trendy Pet
Authors: Amsler E. , Bayrou O. , Pecquet C. , Francès C.
Published: June 2012

Skin contact with animal hair may induce contact urticaria (syndrome) or protein contact dermatitis. We report here 5 cases of dermatitis due to contact with ferrets kept as pets. The nature of the skin lesions, i.e. eczematous dermatitis, as well as the history of our 5 cases point to protein contact dermatitis. Further studies are requested to confirm this hypothesis and to identify the mechanisms and allergens. Physicians must be aware of the possibility of contact dermatitis with ferrets, especially when the patient has no previous history of atopic dermatitis and presents dermatitis of the neck, arm and around mouth.
Neutrophil Extracellular Trap (NET) Impact on Deep Vein Thrombosis
Authors: Fuchs Tobias A. , Brill Alexander , Wagner Denisa D.
Published: June 2012

Deep vein thrombosis (DVT) is a major health problem that requires improved prophylaxis and treatment. Inflammatory conditions such as infection, cancer, and autoimmune diseases are risk factors for DVT. We and others have recently shown that extracellular DNA fibers produced in inflammation and known as neutrophil extracellular traps (NETs) contribute to experimental DVT. NETs stimulate thrombus formation and coagulation and are abundant in thrombi in animal models of DVT. It appears that, in addition to fibrin and von Willebrand factor, NETs represent a third thrombus scaffold. Here, we review how NETs stimulate thrombosis and discuss known and potential interactions of NETs with endothelium, platelets, red blood cells, and coagulation factors and how NETs could influence thrombolysis. We propose that drugs that inhibit NET formation or facilitate NET degradation may prevent or treat DVT.
Endothelial Cells Require Related Transcription Enhancer Factor-1 for Cell–Cell Connections Through the Induction of Gap Junction Proteins
Authors: An Xiaojin , Jin Yi , Philbrick Melissa J. , Wu Jiaping , Messmer-Blust Angela , Song Xiaoxiao , Cully Brittany L. , He Ping , Xu Ming , Duffy Heather S. , Li Jian
Published: June 2012

Objective—

Capillary network formation represents a specialized endothelial cell function and is a prerequisite to establish a continuous vessel lumen. Formation of endothelial cell connections that form the vascular structure is regulated, at least in part, at the transcriptional level. We report here that related transcription enhancer factor-1 (RTEF-1) plays an important role in vascular structure formation.

Methods and Results—

Knockdown of RTEF-1 by small interfering RNA or blockage of RTEF-1 function by the transcription enhancer activators domain decreased endothelial connections in a Matrigel assay, whereas overexpression of RTEF-1 in endothelial cells resulted in a significant increase in cell connections and aggregation. In a model of oxygen-induced retinopathy, endothelial-specific RTEF-1 overexpressing mice had enhanced angiogenic sprouting and vascular structure remodeling, resulting in the formation of a denser and more highly interconnected superficial capillary plexus. Mechanistic studies revealed that RTEF-1 induced the expression of functional gap junction proteins including connexin 43, connexin 40, and connexin 37. Blocking connexin 43 function inhibited RTEF-1–induced endothelial cell connections and aggregation.

Conclusion—

These findings provide novel insights into the transcriptional control of endothelial function in the coordination of cell–cell connections.
Mast Cells Induce Vascular Smooth Muscle Cell Apoptosis via a Toll-Like Receptor 4 Activation Pathway
Authors: den Dekker Wijnand K. , Tempel Dennie , Bot Ilze , Biessen Erik A. , Joosten Leo A. , Netea Mihai G. , van der Meer Jos W. M. , Cheng Caroline , Duckers Henricus J.
Published: June 2012

Objective—

Activated mast cells (MCs) release chymase, which can induce vascular smooth muscle cell (VSMC) apoptosis leading to plaque destabilization. Because the mechanism through which MCs release chymase in atherosclerosis is unknown, we studied whether MC-associated VSMC apoptosis is regulated by toll-like receptor 4 (TLR4) signaling.

Methods and Results—

Local recruitment and activation of MCs reduced VSMC content specifically in the cap region of vulnerable plaques in apolipoprotein E knockout mice. Cotreatment with the TLR4 antagonist
Bartonella quintana
lipopolysaccharide prevented this VSMC loss, suggesting an important role for TLR4 signaling in MC-induced VSMC apoptosis. Coculture of VSMCs with MCs activated by the TLR4 agonist
Escherichia coli
lipopolysaccharide increased VSMC apoptosis. Apoptosis was inhibited by TLR4 and chymase blockers, indicating that TLR4 signaling is involved in chymase release in MCs. This pathway was mediated via interleukin-6 because interleukin-6 promoted MC-associated VSMC apoptosis, which was inhibited by blocking chymase release. In addition, TLR4 activation in MCs induced interleukin-6 production, which was reduced by preincubation with either
B. quintana
lipopolysaccharide or an anti-TLR4 antibody.

Conclusion—

We show that MCs promote VSMC apoptosis in vivo. In addition, TLR4 signaling is important in chymase release in MCs and, therefore, in plaque destabilization by regulating VSMC apoptosis.
Fractalkine Activates a Signal Transduction Pathway Similar to P2Y
12
and Is Associated With Impaired Clopidogrel Responsiveness
Authors: Flierl Ulrike , Fraccarollo Daniela , Lausenmeyer Eva , Rosenstock Tim , Schulz Christian , Massberg Steffen , Bauersachs Johann , Schäfer Andreas
Published: June 2012

Objective—

Fractalkine (FKN) activates a G
αi
protein–coupled signaling pathway similar to the one activated by ADP via P2Y
12
, which is the drug target of clopidogrel. FKN levels are increased under several disease conditions associated with impaired clopidogrel responsiveness.

Methods and Results—

Blood samples were obtained from healthy volunteers and from 40 patients under chronic clopidogrel treatment. FKN reduced prostaglandin E1–induced vasodilator-stimulated phosphoprotein phosphorylation by ≈25% (
P
<0.01) at least partially mimicking the effect of ADP via P2Y
12
. In vitro, FKN increased platelet reactivity index in clopidogrel-treated patients indicating potential activation of downstream targets of P2Y
12
. When stratifying patients by their FKN levels, patients within the highest quartile of FKN (2042±25 pg/mL) had the weakest response to clopidogrel (platelet reactivity index, 68±4%), and patients within the lowest quartile (479±50 pg/mL) had the strongest response (platelet reactivity index, 48±7%;
P
=0.0106). FKN by itself induced phosphoinositide 3-kinase activation leading to Akt phosphorylation at Ser
473
(
P
<0.01 versus basal).

Conclusion—

In addition to desensitizing platelets to prostaglandin E1 via G
αi
, FKN induces phosphoinositide 3-kinase–dependent Akt phosphorylation via a G
βγ
protein similar to ADP signaling through P2Y
12
. FKN increased the platelet ADP response in clopidogrel-treated patients. Once released from an atherosclerotic lesion, this mechanism could contribute locally to impaired clopidogrel responsiveness at the vulnerable plaque.
Selective β
2
-Adrenoreceptor Stimulation Attenuates Myocardial Cell Death and Preserves Cardiac Function After Ischemia–Reperfusion Injury
Authors: Bhushan Shashi , Kondo Kazuhisa , Predmore Benjamin L. , Zlatopolsky Maxim , King Adrienne L. , Pearce Claire , Huang Hui , Tao Ya-Xiong , Condit Marah E. , Lefer David J.
Published: June 2012

Objective—

β
2
-adrenoreceptor activation has been shown to protect cardiac myocytes from cell death. We hypothesized that acute β
2
-adrenoreceptor stimulation, using arformoterol (ARF), would attenuate myocardial ischemia/reperfusion (R) injury via NO synthase activation and cause a subsequent increase in NO bioavailability.

Methods and Results—

Male C57BL/6J and endothelial NO synthase (eNOS) knockout mice were subjected to 45 minutes of myocardial ischemia and 24 hours of R. ARF or vehicle was administered 5 minutes before R. Serum troponin-I was measured, and infarct size per area-at-risk was evaluated at 24 hours of R. Echocardiography was performed at baseline and 2 weeks after R. Myocardial cAMP, protein kinase A, eNOS/Akt phosphorylation status, and NO metabolite levels were assayed. ARF (1 µg/kg) reduced infarct size per area-at-risk by 53.1% (
P
<0.001 versus vehicle) and significantly reduced troponin-I levels (
P
<0.001 versus vehicle). Ejection fraction was significantly preserved in ARF-treated hearts compared with vehicle hearts at 2 weeks of R. Serum cAMP and nuclear protein kinase A C-α increased 5 and 15 minutes after ARF injection, respectively (
P
<0.01). ARF increased Akt phosphorylation at Thr
308
(
P
<0.001) and Ser
473
(
P
<0.01), and eNOS phosphorylation at Ser
1177
(
P
<0.01). ARF treatment increased heart nitrosothiol levels (
P
<0.001) at 15 min after injection. ARF failed to reduce infarct size in eNOS
−/−
mice.

Conclusion—

Our results indicate that β
2
-adrenoreceptor stimulation activates cAMP, protein kinase A, Akt, and eNOS and augments NO bioavailability. Activation of this prosurvival signaling pathway attenuates myocardial cell death and preserves cardiac function after ischemia/reperfusion.
Extrahepatic High-Density Lipoprotein Receptor SR-BI and ApoA-I Protect Against Deep Vein Thrombosis in Mice
Authors: Brill Alexander , Yesilaltay Ayce , De Meyer Simon F. , Kisucka Janka , Fuchs Tobias A. , Kocher Olivier , Krieger Monty , Wagner Denisa D.
Published: June 2012

Objective—

Deep vein thrombosis (DVT) and pulmonary embolism are frequent causes of morbidity and mortality. The goal of our study was to determine whether plasma high-density lipoprotein (HDL), which inversely correlates with the risk of cardiovascular events, affects DVT.

Methods and Results—

Using a murine DVT model of inferior vena cava stenosis, we demonstrated that deficiency of the HDL receptor, scavenger receptor class B type I (SR-BI), promotes venous thrombosis. As SR-BI
−/−
mice have increased plasma cholesterol levels and abnormal HDL particles, we tested SR-BI
−/−
mice with an SR-BI liver transgene that normalizes both parameters. These mice also exhibited increased susceptibility to DVT, indicating a protective role of extrahepatic SR-BI. Mice lacking the major HDL apolipoprotein apoA-I or endothelial nitric oxide synthase (eNOS) (a downstream target of endothelial SR-BI signaling) also had a prothrombotic phenotype. Intravenous infusion of human apoA-I, an HDL component and SR-BI ligend, prevented DVT in wild-type but not SR-BI
−/−
or eNOS
−/−
mice, suggesting that its effect is mediated by SR-BI and eNOS. Intravenous apoA-I infusion abolished histamine-induced platelet–endothelial interactions, which are important for DVT initiation.

Conclusion—

An apoA-I (HDL)–SR-BI–eNOS axis is highly protective in DVT and may provide new targets for prophylaxis and treatment of venous thrombosis.
MAPK Phosphorylation of Connexin 43 Promotes Binding of Cyclin E and Smooth Muscle Cell Proliferation
Authors: Johnstone Scott R. , Kroncke Brett M. , Straub Adam C. , Best Angela K. , Dunn Clarence A. , Mitchell Leslie A. , Peskova Yelena , Nakamoto Robert K. , Koval Michael , Lo Cecilia W. , Lampe Paul D. , Columbus Linda , Isakson Brant E.
Published: June 2012

Rationale:

Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.

Objective:

To investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation.

Methods and Results:

We show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE
−/−
) mice and in C57Bl/6 mice treated with platelet-derived growth factor–BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43
CT
) and produced null phosphorylation Ser>Ala (Cx43
MK4A
/Cx43
CTMK4A
) and phospho-mimetic Ser>Asp (Cx43
MK4D
/Cx43
CTMK4D
) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43
+/+
) and Cx43 null (Cx43
−/−
) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.

Conclusions:

We identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.
C1q/Tumor Necrosis Factor-Related Protein-3, a Newly Identified Adipokine, Is a Novel Antiapoptotic, Proangiogenic, and Cardioprotective Molecule in the Ischemic Mouse Heart
Authors: Yi Wei , Sun Yang , Yuan Yuexing , Lau Wayne Bond , Zheng Qijun , Wang Xiaoliang , Wang Yajing , Shang Xiying , Gao Erhe , Koch Walter J. , Ma Xin-Liang
Published: June 2012

Background—

Obesity and diabetes mellitus adversely affect postischemic heart remodeling via incompletely understood mechanisms. C1q/tumor necrosis factor–related protein-3 (CTRP3) is a newly identified adipokine exerting beneficial metabolic regulation, similar to adiponectin. The aim of the present study was to determine whether CTRP3 may regulate postischemic cardiac remodeling and cardiac dysfunction, and, if so, to elucidate the underlying mechanisms.

Methods and Results—

Male adult mice were subjected to myocardial infarction (MI) via left anterior descending coronary artery occlusion. Both the effect of MI on endogenous CTRP3 expression/production and the effect of exogenous CTRP3 (adenovirus or recombinant CTRP3) replenishment on MI injury were investigated. MI significantly inhibited adipocyte CTRP3 expression and reduced the plasma CTRP3 level, reaching a nadir 3 days after MI. CTRP3 replenishment improved survival rate (
P
<0.05), restored cardiac function, attenuated cardiomyocyte apoptosis, increased revascularization, and dramatically reduced interstitial fibrosis (all
P
<0.01). CTRP3 replenishment had no significant effect on cardiac AMP-activated protein kinase phosphorylation but significantly increased Akt phosphorylation and expression of hypoxia inducing factor-1α and vascular endothelial growth factor. Surprisingly, treatment of human umbilical vascular endothelial cells with CTRP3 did not directly affect nitric oxide production or tube formation. However, preconditioned medium from CTRP3-treated cardiomyocytes significantly enhanced human umbilical vascular endothelial cell tube formation, an effect blocked by either pretreatment of cardiomyocytes with a PI3K inhibitor or pretreatment of human umbilical vascular endothelial cells with a vascular endothelial growth factor inhibitor. Finally, the protective effect of adipocyte-conditioned medium against hypoxia-induced cardiomyocyte injury is significantly blunted when CTRP3 is knocked down.

Conclusion—

CTRP3 is a novel antiapoptotic, proangiogenic, and cardioprotective adipokine, the expression of which is significantly inhibited after MI.