bluuebunny/crossref_metadata_2025 huggingface dataset:
Tetraarsenic Hexoxide Induces Beclin-1-Induced Autophagic Cell Death as well as Caspase-Dependent Apoptosis in U937 Human Leukemic Cells
Authors: Han Min Ho , Lee Won Sup , Lu Jing Nan , Yun Jeong Won , Kim GonSup , Jung Jin Myung , Kim Gi-Young , Lee Su-Jae , Kim Wun-Jae , Choi Yung Hyun
Published: September 2011

Tetraarsenic hexaoxide (As4O6) has been used in Korean folk remedy for the treatment of cancer since the late 1980s, and arsenic trioxide (As2O3) is currently used as a chemotherapeutic agent. However, evidence suggests that As4O6-induced cell death pathway was different from that of As2O3. Besides, the anticancer effects and mechanisms of As4O6are not fully understood. Therefore, we investigated the anticancer activities of As4O6on apoptosis and autophagy in U937 human leukemic cells. The growth of U937 cells was inhibited by As4O6treatment in a dose- and a time-dependent manner, and IC50for As4O6was less than 2 μM. As4O6induced caspase-dependent apoptosis and Beclin-1-induced autophagy, both of which were significantly attenuated by Bcl-2 augmentation and N-acetylcysteine (NAC) treatment. This study suggests that As4O6should induce Beclin-1-induced autophagic cell death as well as caspase-dependent apoptosis and that it might be a promising agent for the treatment of leukemia.
Factors Implicated in Radiation Therapy Failure and Radiosensitization of Prostate Cancer
Authors: Bonkhoff Helmut
Published: September 2011

Tissue markers may be helpful in enhancing prediction of radiation therapy (RT) failure of prostate cancer (PCa). Among the various biomarkers tested in Phase III randomized trials conducted by the Radiation Therapy Oncology Group, p16, Ki-67, MDM2, COX-2, and PKA yielded the most robust data in predicting RT failure. Other pathways involved in RT failure are also implicated in the development of castration-resistant PCa, including the hypersensitive androgen receptor, EGFR, VEGF-R, and PI3K/Akt. Most of them are detectable in PCa tissue even at the time of initial diagnosis. Emerging evidence suggests that RT failure of PCa results from a multifactorial and heterogeneous disease process. A number of tissue markers are available to identify patients at high risk to fail RT. Some of these markers have the promise to be targeted by drugs currently available to enhance the efficacy of RT and delay disease progression.
Wind‐Induced Vibration Control of Dalian International Trade Mansion by Tuned Liquid Dampers
Authors: Li Hong-Nan , Yi Ting-Hua , Jing Qin-Yang , Huo Lin-Sheng , Wang Guo-Xin
Published: September 2011

This paper focuses on the wind‐induced vibration control of the Dalian international trade mansion (DITM) by using the tuned liquid dampers (TLDs). To avoid the intensive computationally demanding problem caused by tens of thousand of degrees of freedom (DOF) of the structure in the numerical analysis, the three‐dimension finite element model of the DITM is first simplified to the equivalent series multi‐DOF system. The wind loading is subsequently simulated by the Davenport model according to the structural environmental condition where the actual samples of wind speed are measured. Following that, the shallow‐ and deep‐water wave theories are applied to model the liquid sloshing inside TLDs, the tank sizing, and required water depth, and numbers of TLDs are given according to the numerical results of different cases. Comparisons between uncontrolled and controlled displacement and acceleration responses of the DITM under wind forces show that the designed shallow tank has higher efficiency than the deep one, which can effectively reduce the structural response amplitudes and enhance the comfortableness of the mansion. The preliminary TLD design procedure presented in this paper could be applied as a reference to the analysis and design of the wind‐induced vibration for high‐rise buildings using the TLD.
Quantifying the Role of Angiogenesis in Malignant Progression of Gliomas: In Silico Modeling Integrates Imaging and Histology
Authors: Swanson Kristin R. , Rockne Russell C. , Claridge Jonathan , Chaplain Mark A. , Alvord Ellsworth C. , Anderson Alexander R.A.
Published: September 2011

Gliomas are uniformly fatal forms of primary brain neoplasms that vary from low- to high-grade (glioblastoma). Whereas low-grade gliomas are weakly angiogenic, glioblastomas are among the most angiogenic tumors. Thus, interactions between glioma cells and their tissue microenvironment may play an important role in aggressive tumor formation and progression. To quantitatively explore how tumor cells interact with their tissue microenvironment, we incorporated the interactions of normoxic glioma cells, hypoxic glioma cells, vascular endothelial cells, diffusible angiogenic factors, and necrosis formation into a first-generation, biologically based mathematical model for glioma growth and invasion. Model simulations quantitatively described the spectrum of in vivo dynamics of gliomas visualized with medical imaging. Furthermore, we investigated how proliferation and dispersal of glioma cells combine to induce increasing degrees of cellularity, mitoses, hypoxia-induced neoangiogenesis and necrosis, features that characterize increasing degrees of “malignancy,” and we found that changes in the net rates of proliferation (ρ) and invasion (D) are not always necessary for malignant progression. Thus, although other factors, including the accumulation of genetic mutations, can change cellular phenotype (e.g., proliferation and invasion rates), this study suggests that these are not required for malignant progression. Simulated results are placed in the context of the current clinical World Health Organization grading scheme for studying specific patient examples. This study suggests that through the application of the proposed model for tumor–microenvironment interactions, predictable patterns of dynamic changes in glioma histology distinct from changes in cellular phenotype (e.g., proliferation and invasion rates) may be identified, thus providing a powerful clinical tool. Cancer Res; 71(24); 7366–75. ©2011 AACR.
β1-Integrin: A Potential Therapeutic Target in the Battle against Cancer Recurrence
Authors: Barkan Dalit , Chambers Ann F.
Published: September 2011

Primary cancer treatment, involving both local and often systemic adjuvant therapy, is often successful, especially if the cancer is detected at an early stage of progression. However, for some patients, the cancer may recur either locally or as distant metastases, in some cases many years after apparently successful primary treatment. Significant tumor dormancy has been documented in several cancers, such as breast, melanoma, and renal cancer. Tumor dormancy has long been recognized as an important problem in management of cancer patients. Recent work has clarified biologic aspects of tumor dormancy and has shown that dormant tumor cells may be resistant to cytotoxic chemotherapy and radiation. This work has led to recognition of a key role for β1-integrin in regulating the switch from a dormant state to active proliferation and metastasis. Here we discuss the role of β1-integrin and its signaling partners in regulating the dormant phenotype. We also consider possible therapeutic approaches, such as small molecules or antibodies (ATN-161, volociximab, and JSM6427), directed against β1-integrin signaling to target dormant cancer cells and to prevent metastatic recurrence. Clin Cancer Res; 17(23); 7219–23. ©2011 AACR.
A Novel, Selective Inhibitor of Fibroblast Growth Factor Receptors That Shows a Potent Broad Spectrum of Antitumor Activity in Several Tumor Xenograft Models
Authors: Zhao Genshi , Li Wei-ying , Chen Daohong , Henry James R. , Li Hong-Yu , Chen Zhaogen , Zia-Ebrahimi Mohammad , Bloem Laura , Zhai Yan , Huss Karen , Peng Sheng-bin , McCann Denis J.
Published: September 2011

The fibroblast growth factor receptors (FGFR) are tyrosine kinases that are present in many types of endothelial and tumor cells and play an important role in tumor cell growth, survival, and migration as well as in maintaining tumor angiogenesis. Overexpression of FGFRs or aberrant regulation of their activities has been implicated in many forms of human malignancies. Therefore, targeting FGFRs represents an attractive strategy for development of cancer treatment options by simultaneously inhibiting tumor cell growth, survival, and migration as well as tumor angiogenesis. Here, we describe a potent, selective, small-molecule FGFR inhibitor, (R)-(E)-2-(4-(2-(5-(1-(3,5-Dichloropyridin-4-yl)ethoxy)-1H-indazol-3yl)vinyl)-1H-pyrazol-1-yl)ethanol, designated as LY2874455. This molecule is active against all 4 FGFRs, with a similar potency in biochemical assays. It exhibits a potent activity against FGF/FGFR-mediated signaling in several cancer cell lines and shows an excellent broad spectrum of antitumor activity in several tumor xenograft models representing the major FGF/FGFR relevant tumor histologies including lung, gastric, and bladder cancers and multiple myeloma, and with a well-defined pharmacokinetic/pharmacodynamic relationship. LY2874455 also exhibits a 6- to 9-fold in vitro and in vivo selectivity on inhibition of FGF- over VEGF-mediated target signaling in mice. Furthermore, LY2874455 did not show VEGF receptor 2–mediated toxicities such as hypertension at efficacious doses. Currently, this molecule is being evaluated for its potential use in the clinic. Mol Cancer Ther; 10(11); 2200–10. ©2011 AACR.
Effects of Long-Acting Methylphenidate in Adults with Attention Deficit Hyperactivity Disorder: A Study with Paired-Pulse Transcranial Magnetic Stimulation
Authors: Schneider Marc K.F. , Retz Wolfgang , Gougleris Gavril , Verhoeven Willem M.A. , Tulen Joke H.M. , Rösler Michael
Published: September 2011

Background: Methylphenidate improves attention deficits, hyperactivity and impulsivity in attention deficit hyperactivity disorder (ADHD). Recent investigations into motor cortex excitability with paired-pulse transcranial magnetic stimulation (ppTMS) technique have shown inhibition deficits in ADHD which correlate with clinical symptomatology. Therefore, we investigated the neurophysiological effects of long-acting methylphenidate (LA-Mph) with the ppTMS technique in adult patients with ADHD. Methods: Thirteen right-handed adult ADHD patients who were first diagnosed with ADHD were included in this ppTMS study. Measurements took place before and during treatment with LA-Mph (30–54 mg/day). Statistical analyses were performed to investigate treatment effects and correlations with clinical symptomatology. Results: LA-Mph significantly decreased the relative short intracortical motor inhibition (SICI) magnetically evoked potential (MEP) amplitude at 3-ms interstimulus interval (conditioned/unconditioned MEP amplitude: 0.83 ± 0.76 drug-free vs. 0.29 ± 0.19 with LA-Mph; p = 0.020). The relative intracortical facilitation MEP amplitude at 11 ms interstimulus interval (conditioned/unconditioned MEP amplitude: 1.51 ± 0.92 drug-free vs. 1.79 ± 0.95 with LA-Mph) was not significantly increased. The reduced relative SICI MEP amplitude with LA-Mph correlated significantly with the improvement of the psychopathological ADHD self-rating total scores (p = 0.046). Conclusion: These results show that in adult patients with ADHD, LA-Mph significantly improves motor disinhibition and might have differential stabilizing effects on motor hyperexcitability.
Polymorphisms of the 5-HT2A Receptor Gene and Clinical Response to Olanzapine in Paranoid Schizophrenia
Authors: Olajossy-Hilkesberger Luiza , Godlewska Beata , Schosser-Haupt Alexandra , Olajossy Marcin , Wojcierowski Jacek , Landowski Jerzy , Marmurowska-Michałowska Halina , Kasper Siegfried
Published: September 2011

Background: 5-HT2A receptor is strongly implicated in the mode of action of atypical antipsychotic drugs. The aim of the study was to investigate whether the 5-HT2A receptor gene’s polymorphisms (His452Tyr and T102C) have an influence on the response to olanzapine in patients with schizophrenia. Methods: We studied 99 Caucasian schizophrenia patients treated with olanzapine. Psychopathology was measured before and after 6 weeks of treatment. Clinical improvement was quantified as change in Positive and Negative Syndrome Scale (PANSS) total scores and subscores as shown by percentage improvement below the baseline score. The clinical response to antipsychotic treatment was defined as 30% improvement from baseline in PANSS scores. Results: The His/Tyr polymorphism was significantly associated with a percentage improvement in PANSS positive symptom subscore (better response in His/His homozygotes; p < 0.05) after treatment with olanzapine. As for the T102C polymorphism, a better response in terms of PANSS positive subscore improvement was observed for C/C homozygotes (p < 0.01). A significant association of 5-HT2A genotype distribution of the T102C polymorphism with a categorical measure of response, but only in terms of PANSS positive symptom subscores, was observed (p < 0.01). Conclusions: Variations in the 5-HT2A receptor gene may influence individual and particularly positive symptom response to olanzapine.
Cytogenetic Effects of Valproic Acid and Ziprasidone in Human Lymphocyte Cultures
Authors: Karapidaki Irine , Ekonomopoulou Maria T. , Akritopoulou Kyriaki , Anestakis Doxakis , Iakovidou-Kritsi Zafiroula
Published: September 2011

Background/Aims: Valproic acid or valproate (VA) is an anticonvulsant and mood-stabilizing drug primarily used in the treatment of epilepsy and bipolar disorder. Ziprasidone (ZPN) is an atypical antipsychotic drug used mainly for the treatment of schizophrenia. Methods: This study is a part of our investigation on the cytogenetic effects of psychotropic drugs. Lymphocytes of peripheral blood cultures from 3 healthy donors treated with VA, ZPN and combinations of these (at concentrations equivalent to the oral doses) were used for the estimation of sister chromatid exchanges (SCEs) and the proliferation rate index (PRI). As a biomarker of genotoxicity, we used SCEs, one of the most sensitive methods reflecting DNA damage and/or subsequent DNA repair, and as a marker of cytostaticity we estimated the PRI. Results: All treated lymphocyte cultures showed a statistically significant increase in SCE frequency and a significant decrease in PRI values (p < 0.001). The combined effect of the drugs induced similar or more intense results, without reaching levels indicating synergistic action. Conclusion: This in vitro study investigated the cytogenetic activity of monotherapy vs. combined chronic drug exposure, and could form a catalyst for further investigations aiming to develop more efficacious therapy with decreased cytogenetic damage.
Neurohormonal Activation in Acute Heart Failure: Results from VERITAS
Authors: Milo-Cotter Olga , Cotter-Davison Beth , Lombardi Carlo , Sun Hengrui , Bettari Luca , Bugatti Silvia , Rund Michele , Metra Marco , Kaluski Edo , Kobrin Isaac , Frey Aline , Rainisio Maurizio , McMurray John J.V. , Teerlink John R. , Cotter-Davison Gad
Published: September 2011

Objectives: Recent heart failure studies have suggested that inflammatory and immune system activation are associated with increased levels of cytokines, chemokines and inflammatory proteins during acutely decompensated heart failure. The objectives of this substudy were to evaluate the role of neurohormonal and inflammatory activation in the pathogenesis and outcome of acute heart failure (AHF) and the correlation between biomarker levels and clinical outcomes. Methods: Serum levels of B-type natriuretic peptide-32 (BNP-32), endothelin-1 (ET-1), norepinephrine, troponins I and T, C-reactive protein (CRP), von Willebrand factor, plasminogen activator inhibitor-1, interleukin-6 (IL-6) and tissue plasminogen activator (TPA) were measured at baseline, 24 and 48 h and 7 and 30 days in 112 patients with AHF recruited to the Value of Endothelin Receptor Inhibition with Tezosentan in Acute Heart Failure Study neurohormonal substudy. Results: On univariable analysis, CRP, BNP and ET-1 were predictive of worsening heart failure by day 30; when considered together, only CRP and BNP were significantly associated with this outcome. On adjustment for age, baseline blood pressure, serum sodium and serum creatinine, only age and BNP remained significant. CRP, IL-6 and TPA levels were significantly correlated with 180-day mortality on univariable analysis. Conclusion: Circulating markers of inflammation may be useful in gauging prognosis in patients with AHF.
Identification of CD133+ Cells in Pituitary Adenomas
Authors: Yunoue Shunji , Arita Kazunori , Kawano Hiroto , Uchida Hiroyuki , Tokimura Hiroshi , Hirano Hirofumi
Published: September 2011

Stem-like cells in tumors are capable of self-renewal and pluri-differentiation; they are thought to play important roles in tumor initiation and maintenance. Stem-like cells in malignant glioma express CD133. We examined samples from human pituitary adenoma, a generally benign neoplasm, for CD133 expression using routine immunohistochemical and biochemical methods. Our study of 70 pituitary adenomas (clinically nonfunctioning adenomas and growth hormone-, prolactin-, adrenocorticotropic hormone-, and thyroid-stimulating hormone-producing adenomas) showed that 18 (25.7%) expressed CD133. This rate was higher in clinically nonfunctioning (33.3%) than functioning adenomas (12.0%) (p = 0.085). Real-time PCR assay revealed the expression of CD133 mRNA in samples immunohistochemically positive for CD133. Neither the patient age and gender, nor the tumor size or postoperative recurrence rate correlated with CD133 positivity. CD133+ cells ubiquitously coexpressed CD34, nestin, and VEGFR2 (KDL1). S-100 and GFAP were not coexpressed with CD133. Chromogranin A, Pit-1, SF-1, and NeuroD1 were immune-negative, indicating that CD133+ cells did not have the potential to differentiate into functional endocrine cells. Our data suggest that the expression of CD133 in pituitary adenomas is related to immature endothelial progenitor cells that may play a role in the neovascularization of pituitary adenomas. Further studies are needed to elucidate the significance of CD133+ cells with respect to neovascularization and their sustainable growth in pituitary adenomas.
Malnutrition in Infancy as a Susceptibility Factor for Temporal Lobe Epilepsy in Adulthood Induced by the Pilocarpine Experimental Model
Authors: Cabral Francisco Romero , Priel Margareth Rose , Silva Araujo Bruno Henrique , Brito Torres Laila , de Lima Eliangela , Gurgel do Vale Tiago , Pereira Felipe , Alves de Amorim Henrique , Abrão Cavalheiro Esper , Amado Scerni Débora , Naffah-Mazzacoratti Maria da Graça
Published: September 2011

Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreover, this condition could increase the chances of developing neurological diseases, such as epilepsy. We analyzed the effects of early-life malnutrition on susceptibility to epileptic seizures induced by the pilocarpine model of epilepsy. Wistar rat pups were kept on a starvation regimen from day 1 to day 21 after birth. At day 60, 16 animals (8 = well-nourished; 8 = malnourished) were exposed to the pilocarpine experimental model of epilepsy. Age-matched well-nourished (n = 8) and malnourished (n = 8) rats were used as controls. Animals were video-monitored over 9 weeks. The following behavioral parameters were evaluated: first seizure threshold (acute period of the pilocarpine model); status epilepticus (SE) latency; first spontaneous seizure latency (silent period), and spontaneous seizure frequency during the chronic phase. The cell and mossy fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed that the malnourished animals required a lower pilocarpine dose in order to develop SE (200 mg/kg), lower latency to reach SE, less time for the first spontaneous seizure and higher seizure frequency, when compared to well-nourished pilocarpine rats. Histopathological findings revealed a significant cell density reduction in the CA1 region and intense MFS among the malnourished animals. Our data indicate that early malnutrition greatly influences susceptibility to seizures and behavioral manifestations in adult life. These findings suggest that malnutrition in infancy reduces the threshold for epilepsy and promotes alterations in the brain that persist into adult life.
Gender and Ethnic Disparities in Incidence and Survival of Squamous Cell Carcinoma of the Oral Tongue, Base of Tongue, and Tonsils: A Surveillance, Epidemiology and End Results Program-Based Analysis
Authors: Saba Nabil F. , Goodman Michael , Ward Kevin , Flowers Chris , Ramalingam Suresh , Owonikoko Taofeek , Chen Amy , Grist William , Wadsworth Trad , Beitler Jonathan J. , Khuri Fadlo R. , Shin Dong M.
Published: September 2011

Background: Squamous cell carcinomas (SCC) of the oral tongue (OT) and of the base of the tongue and tonsils (BTT) differ with respect to etiology, treatment and prognosis. Human papillomavirus has been linked to the increased incidence of BTT, yet, the trends in incidence of BTT and OT tumors among gender and ethnic origin groups have not been well examined. We sought to examine the trend in gender-, ethnic origin- and age-specific incidence of these tumors over time. Methods: Data were obtained from the Surveillance, Epidemiology and End Results Program of the US National Cancer Institute. We examined temporal trends in sex- and ethnic origin-specific incidence of SCC by calculating the annual percent changes followed by joinpoint analyses evaluating changes in trend. Results: While BTT increased in age-adjusted rates among white males with a more pronounced increase observed in the mid-1990s, white females experienced a significant increase in incidence of OT tumors. Patients with advanced OT carcinoma had a significantly lower survival compared to those with advanced BTT disease; however, patients with early-stage OT tumors had a better survival compared to patients with BTT. Conclusions: While the increase in incidence of BTT tumors in white men is likely human papillomavirus driven, more studies are needed to elucidate the increasing incidence of OT tumors in white women. The differences in outcomes across ethnic origin groups are also described and discussed.
Randomised Controlled Trial of the Efficacy of a High-Fluoride Gel Self-Applied by Toothbrushing in Children at High Caries Risk
Authors: Stokes E. , Ashcroft A. , Burnside G. , Mohindra T. , Pine C.M.
Published: September 2011

The primary objective of this clinical trial was to assess the caries-preventive efficacy of 2 years of twice weekly supervised brushing with a self-applied gel containing 12,500 ppm fluoride on schooldays compared with weekly supervised use in children at high caries risk (with prior caries experience on first permanent molars). The secondary objective was to assess efficacy compared with similar children who continued with their usual oral hygiene care. This was a single-centre, single-blind, randomised, parallel-groups trial comprising two test groups and one untreated control group. 1,075 pupils aged 12–13 years at baseline received a baseline and final examination 2 years later. For all children completing the trial no significant difference was found between groups. For children compliant with study protocol no significant difference was found in the primary outcome (D1FS caries increment), but significant differences were found between the three groups overall in the secondary outcome, D3FT caries increment, with a significant pairwise difference between control and twice per week gel brushing (29%, p = 0.023 D3FT visual + fibre-optic transillumination). Analysis of the relationship between number of gel applications and caries showed that children who brushed with the gel at least 60 times over a 2-year period developed significantly fewer carious lesions into dentine than children who followed their usual oral hygiene routine. Some caution is needed as greatest benefit was shown by compliant children. Where schools are co-operative, it is recommended that the gel be used twice a week within a school-based programme over a 2-year period.
Crescentic Glomerulonephritis in IgA Multiple Myeloma: A Case Report
Authors: Moscoso-Solorzano Grace T. , Madureira-Silva Marcus V. , Balda Carlos , Franco Marcello F. , Mastroianni-Kirsztajn Gianna
Published: September 2011

Background: There are few reports of glomerulonephritis (GN) with crescents and a rapidly progressive course that lead to a diagnosis of a previously unsuspected B-cell dyscrasia. Case Presentation: We report a case of rapidly progressive GN: the patient showed no evidence of etiology at the time of biopsy and was diagnosed as IgA multiple myeloma (MM) during investigation based on a renal biopsy. He presented diffuse proliferative and exudative GN and marked plasma cell infiltration of the kidney. Conclusion: The present case raises the possibility that proliferative GN with crescents may be a rare mode of presentation of MM.
Prothrombin complex concentrate reduces blood loss and enhances thrombin generation in a pig model with blunt liver injury under severe hypothermia
Authors: Rieg Annette , Rossaint Rolf , Braunschweig Till , Spronk Henri , ten Cate Hugo , van Oerle Rene , Tolba Rene , Honickel Markus , Grottke Oliver
Published: September 2011

Although prothrombin complex concentrate (PCC) is increasingly used for the treatment of trauma-induced coagulopathy, few studies have investigated the impact and safety of PCC for this indication. The present study was performed to assess PCC for treatment of coagulopathy after blunt liver injury under severe hypothermia. Coagulopathy in 14 anaesthetised pigs was induced by haemodilution. Subsequently, standardised blunt liver injury was induced under severe hypothermia (32.8–33.2°C). Animals were randomised to receive either PCC (35 IU kg-1) or saline (control). Coagulation was assessed over the following 2 hours by thromboelastometry and thrombin generation. Internal organs were examined to determine presence of emboli. The administration of PCC showed a significant reduction in blood loss (p=0.002 vs. controls) and a significant increase in the rate of survival (p=0.022 vs. controls). Plasma thrombin generation in the PCC group increased considerably above baseline levels, with significant increases in peak thrombin levels and endogenous thrombin potential versus controls throughout the follow-up period. In addition, PT decreased significantly in the PCC group versus the control group. However, only slight improvements in thromboelastometry variables were observed. Histology showed an equal degree of liver injury in both groups, and no thromboembolism. In severely hypothermic pigs, the application of PCC corrected trauma-induced coagulopathy and reduced blood loss. Thus, the infusion of PCC might be a reasonable approach to reduce the need for blood cell transfusion in trauma. Furthermore, the impact and safety of PCC application can be monitored through thrombin generation and thromboelastometry under hypothermia.

Note: This study was performed at the RWTH Aachen University Hospital, Pauwelsstrasse 30, D-52074 Aachen, Germany.
Dendritic cells in atherosclerosis: Functions in immune regulation and beyond
Authors: Manthey Helga , Zernecke Alma
Published: September 2011

Chronic inflammation drives the development of atherosclerosis. Dendritic cells (DCs) are known as central mediators of adaptive immune responses and the development of immunological memory and tolerance. DCs are present in non-diseased arteries, and accumulate within atherosclerotic lesions where they can be localised in close vicinity to T cells. Recent work has revealed important functions of DCs in regulating immune mechanisms in atherogenesis, and vaccination strategies using DCs have been explored for treatment of disease. However, in line with a phenotypical and functional overlap with plaque macrophages vascular DCs were also identified to engulf lipids, thus contributing to lipid burden in the vessel wall and initiation of lesion growth. Furthermore, a function of DCs in regulating cholesterol homeostasis has been revealed. Finally, phenotypically distinct plasmacytoid dendritic cells (pDCs) have been identified within atherosclerotic lesions. This review will dissect the multifaceted contribution of DCs and pDCs to the initiation and progression of atherosclerosis and the experimental approaches utilising DCs in therapeutic vaccination strategies.
Novel recombinant glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 and variants for assessment of anti-ADAMTS13 autoantibodies in patients with thrombotic thrombocytopenic purpura
Authors: Li Dengju , Xiao Juan , Paessler Michele , Zheng X.
Published: September 2011

Immunoglobulin Gs (IgGs) against ADAMTS13 are major causes of acquired (idiopathic) thrombotic thrombocytopenic purpura (TTP). We report here a novel cell-based assay using glycosylphosphatidylinositol (GPI)-anchored ADAMTS13 or variants expressed on cell membrane for assessment of autoantibodies in patients with TTP. We showed that IgGs from all 26 patients with acquired TTP bound to cells expressing a GPI anchored full-length ADAMTS13 (gFL) and a variant truncated after the spacer domain (gS). Also, IgGs from 25/26 (96.7%) of these TTP patients bound to cells expressing a GPI-anchored C-terminal fragment, TSP1 2–8 plus CUB (gT2C). In contrast, none of the 20 healthy blood donors showed detectable binding of their IgGs to the cells expressing gFL, gS, and gT2C. A moderate, but statistically significant correlation was observed between plasma concentrations of anti-ADAMTS13 IgG and positive cells expressing gFL (r=0.65), gS (r=0.67), and gT2C (r=0.42). These results suggest that the microtiter-plate assay and the cell-based assay may detect differential antigenic epitopes. Moreover, antigens clustered on cell membranes may enhance antibody binding affinity, thereby increasing analytical sensitivity. Finally, our assay was able to determine kinetic changes of plasma levels of anti-ADAMTS13 IgGs in TTP patients during plasma therapy. Together, our findings suggest that the novel cell-based assay may be applicable for rapid identification and mapping of anti-ADAMTS13 autoantibodies in patients with acquired TTP.
Recombinant activated protein C attenuates coagulopathy and inflammation when administered early in murine pneumococcal pneumonia
Authors: van ’t Veer Cornelis , Roelofs Joris , Gerlitz Bruce , Grinnell Brian , Levi Marcel , der Poll Tom , Schouten Marcel
Published: September 2011

Recombinant human activated protein C (APC), which has both anticoagulant and anti-inflammatory properties, improves survival of patients with severe sepsis. This beneficial effect is especially apparent in patients with pneumococcal pneumonia. Earlier treatment with APC in sepsis has been associated with a better therapeutic response as compared to later treatment. In a mouse model it was recently confirmed that recombinant murine (rm-)APC decreases coagulation activation and improves survival in pneumococcal pneumonia; however, APC did not impact on the inflammatory response. The aim of this study was to determine the effect of APC treatment instigated early in infection on activation of coagulation and inflammation after induction of pneumococcal pneumonia. Mice were infected intranasally with viable S. pneumoniae. Mice were treated with rm-APC (125 μg) or vehicle intraperitoneally 12 hours after infection and were sacrificed after 20 hours, after which blood and organs were harvested for determination of bacterial outgrowth, coagulation activation and inflammatory markers. In this early treatment model, rm-APC treatment inhibited pulmonary and systemic activation of coagulation as reflected by lower levels of throm-bin-antithrombin complexes and D-dimer. Moreover, rm-APC reduced the levels of a large number of cytokines and chemokines in the lung. When administered early in pneumococcal pneumonia, rm-APC inhibits systemic and pulmonary activation of coagulation and moreover exerts various anti-inflammatory effects in the lung.
Right Ventricular Failure in Idiopathic Pulmonary Arterial Hypertension Is Associated With Inefficient Myocardial Oxygen Utilization
Authors: Wong Yeun Ying , Ruiter Gerrina , Lubberink Mark , Raijmakers Pieter G. , Knaapen Paul , Marcus J. Tim , Boonstra Anco , Lammertsma Adriaan A. , Westerhof Nico , van der Laarse Willem J. , Vonk-Noordegraaf Anton
Published: September 2011

Background—

In idiopathic pulmonary arterial hypertension (IPAH), increased right ventricular (RV) power is required to maintain cardiac output. For this, RV O
2
consumption (MVO
2
) must increase by augmentation of O
2
supply and/or improvement of mechanical efficiency–ratio of power output to MVO
2
. In IPAH with overt RV failure, however, there is evidence that O
2
supply (perfusion) reserve is reduced, leaving only increase in either O
2
extraction or mechanical efficiency as compensatory mechanisms. We related RV mechanical efficiency to clinical and hemodynamic parameters of RV function in patients with IPAH and associated it with glucose metabolism.

Methods and Results—

The patients included were in New York Heart Association (NYHA) class II (n=8) and class III (n=8). They underwent right heart catheterization, MRI, and H
2
15
O-,
15
O
2
-, C
15
O-, and
18
FDG-PET. RV power and O
2
supply were similar in both groups (NYHA class II versus class III: 0.54±0.14 versus 0.47±0.12 J/s and 0.109±0.022 versus 0.128±0.026 mL O
2
/min per gram, respectively). RV O
2
extraction was near-significantly lower in NYHA class II compared with NYHA class III (63±17% versus 75±16%, respectively,
P
=0.10). As a result, MVO
2
was significantly lower (0.066±0.012 versus 0.092±0.010 mL O
2
/min per gram, respectively,
P
=0.006). RV efficiency was reduced in NYHA class III (13.9±3.8%) compared with NYHA class II (27.8±7.6%,
P
=0.001). Septal bowing, measured by MRI, correlated with RV efficiency (
r
=−0.59,
P
=0.020). No relation was found between RV efficiency and glucose uptake rate. RV mechanical efficiency and ejection fraction were closely related (
r
=0.81,
P
<0.001).

Conclusions—

RV failure in IPAH was associated with reduced mechanical efficiency that was partially explained by RV mechanical dysfunction but not by a metabolic shift.
On Trade Wind Cumulus Cold Pools
Authors: Zuidema Paquita , Li Zhujun , Hill Reginald J. , Bariteau Ludovic , Rilling Bob , Fairall Chris , Brewer W. Alan , Albrecht Bruce , Hare Jeff
Published: September 2011

Shallow precipitating cumuli within the easterly trades were investigated using shipboard measurements, scanning radar data, and visible satellite imagery from 2 weeks in January 2005 of the Rain in Cumulus over the Ocean (RICO) experiment. Shipboard rainfall rates of up to 2 mm h−1 were recorded almost daily, if only for 10–30 min typically, almost always from clouds within mesoscale arcs. The precipitating cumuli, capable of reaching above 4 km, cooled surface air by 1–2 K, in all cases lowered surface specific humidities by up to 1.5 g kg−1, reduced surface equivalent potential temperatures by up to 6 K, and were often associated with short-lived increases in wind speed. Upper-level downdrafts were inferred to explain double-lobed moisture and temperature sounding profiles, as well as multiple inversions in wind profiler data. In two cases investigated further, the precipitating convection propagated faster westward than the mean surface wind by about 2–3 m s−1, consistent with a density current of depth ~200 m. In their cold pool recovery zones, the surface air temperatures equilibrated with time to the sea surface temperatures, but the surface air specific humidities stayed relatively constant after initial quick recoveries. This suggested that entrainment of drier air from above fully compensated the moistening from surface latent heat fluxes. Recovery zone surface wind speeds and latent heat fluxes were not higher than environmental values. Nonprecipitating clouds developed after the surface buoyancy had recovered (barring encroachment of other convection). The mesoscale arcs favored atmospheres with higher water vapor paths. These observations differed from those of stratocumulus and deep tropical cumulus cold pools.
A PV Perspective on the Vertical Structure of Mature Midlatitude Cyclones in the Northern Hemisphere
Authors: Čampa Jana , Wernli Heini
Published: September 2011

Development of extratropical cyclones can be seen as an interplay of three positive potential vorticity anomalies: an upper-level stratospheric intrusion, low-tropospheric diabatically produced potential vorticity (PV), and a warm anomaly at the surface acting as a surrogate PV anomaly. This study, based on the interim ECMWF Re-Analysis (ERA-Interim) dataset, quantifies the amplitude of the PV anomalies of mature extratropical cyclones in different regions in the Northern Hemisphere on a climatological basis.

A tracking algorithm is applied to sea level pressure (SLP) fields to identify cyclone tracks. Surface potential temperature anomalies Δθ and vertical profiles of PV anomalies ΔPV are calculated at the time of the cyclones’ minimum SLP in a vertical cylinder around the surface cyclone center. To compare the cyclones’ characteristics they are grouped according to their location and intensity. Composite ΔPV profiles are calculated for each region and intensity class at the time of minimum SLP and during the cyclone intensification phase.

In the mature stage all three anomalies are on average larger for intense than for weak winter cyclones [e.g., 0.6 versus 0.2 potential vorticity units (PVU; 1 PVU = 10−6 K kg−1 m2 s−1) at lower levels, and 1.5 versus 0.5 PVU at upper levels]. The regional variability of the cyclones’ vertical structure and the profile evolution is prominent (cyclones in some regions are more sensitive to the amplitude of a particular anomaly than in other regions). Values of Δθ and low-level ΔPV are on average larger in the western parts of the oceans than in the eastern parts. Results for summer are qualitatively similar, except for distinctively weaker surface Δθ values.
Model Study of Intermediate-Scale Tropical Inertia–Gravity Waves and Comparison to TWP-ICE Campaign Observations
Authors: Evan Stephanie , Alexander M. Joan , Dudhia Jimy
Published: September 2011

A 2-day inertia–gravity wave (IGW) was observed in high-resolution radiosonde soundings of horizontal wind and temperature taken during the 2006 Tropical Warm Pool–International Cloud Experiment (TWP-ICE) experiment in the Darwin area. The wave was observed in the stratosphere above Darwin from 28 January to 5 February. A similar wave event is observed in the European Centre for Medium-Range Weather Forecasts (ECMWF) operational data. A comparison between the characteristics of the IGW derived with the ECMWF data to the properties of the wave derived with the radiosonde data shows that the ECMWF data capture similar structure for this 2-day wave event but with a larger vertical wavelength.

A reverse ray-tracing method is used to localize the source region. Using ECMWF data to define the atmospheric background conditions and wave properties observed in the soundings, it is found that the 2-day wave event originated from deep convection in the Indonesian region around 20 January.

The Weather Research and Forecasting (WRF) modeling system is used to complement the ECMWF data to assess the influence of vertical resolution and initial conditions on the wave structure. The model domain is configured as a tropical channel and the ECMWF analyses provide the north/south boundaries and initial conditions. WRF is used with the same horizontal resolution (40 km) as the operational ECMWF in 2006 while using a finer vertical grid spacing than ECMWF. The model is run from 18 January to 11 February to cover the wave life cycle. Different experiments are also performed to determine the sensitivity of the wave structure to cumulus schemes, initial conditions, and vertical resolution. The 2-day wave properties resulting from the WRF experiments are compared to those retrieved from the radiosonde data and from the ECMWF analyses. It is demonstrated that higher vertical resolution would be required for ECMWF to accurately resolve the vertical structure of the wave and its effect on the middle-atmospheric circulation.
Enhancement of Sea Ice Drift due to the Dynamical Interaction between Sea Ice and a Coastal Ocean
Authors: Nakayama Yoshihiro , Ohshima Kay I. , Fukamachi Yasushi
Published: September 2011

Wind factor, the ratio of sea ice drift speed to surface wind speed, is a key factor for the dynamics of sea ice and is generally about 2%. In some coastal oceans, however, the wind factor tends to be larger near the coast. This study proposes the enhancement mechanism of the sea ice drift caused by the dynamical coupling between sea ice and a coastal ocean. In a coastal ocean covered with sea ice, wind-forced sea ice drift excites coastal trapped waves (shelf waves) and generates fluctuating ocean current. This ocean current can enhance sea ice drift when the current direction is the same as that of the wind-driven drift. The authors consider a simplified setting where spatially uniform oscillating wind drifts sea ice parallel to the coast. When a barotropic long shelf wave is assumed for the ocean response, sea ice drifts driven by wind and ocean are obtained analytically. The ratio of ocean-driven to wind-driven sea ice drifts is used for the evaluation of the oceanic contribution to the enhancement of sea ice drift. The enhancement is mostly determined by the characteristics of the shelf waves, and sea ice drift is significantly enhanced close to the coast with lower-frequency wind forcing. Comparison with the observation off the Sakhalin coast shows that the degree of enhancement of sea ice drift and its characteristic such that larger enhancement occurs near the coast are mostly consistent with our theoretical solution, suggesting that this mechanism is present in the real ocean.
Multidecadal Sea Level and Gyre Circulation Variability in the Northwestern Tropical Pacific Ocean
Authors: Qiu Bo , Chen Shuiming
Published: September 2011

Sea level rise with the trend >10 mm yr−1 has been observed in the tropical western Pacific Ocean over the 1993–2009 period. This rate is 3 times faster than the global-mean value of the sea level rise. Analyses of the satellite altimeter data and repeat hydrographic data along 137°E reveal that this regionally enhanced sea level rise is thermosteric in nature and vertically confined to a patch in the upper ocean above the 12°C isotherm. Dynamically, this regional sea level trend is accompanied by southward migration and strengthening of the North Equatorial Current (NEC) and North Equatorial Countercurrent (NECC). Using a 1½-layer reduced-gravity model forced by the ECMWF reanalysis wind stress data, the authors find that both the observed sea level rise and the NEC/NECC’s southward migrating and strengthening trends are largely attributable to the upper-ocean water mass redistribution caused by the surface wind stresses of the recently strengthened atmospheric Walker circulation. Based on the long-term model simulation, it is further found that the observed southward migrating and strengthening trends of the NEC and NECC began in the early 1990s. In the two decades prior to 1993, the NEC and NECC had weakened and migrated northward in response to a decrease in the trade winds across the tropical Pacific Ocean.
The Form, the Permit and the Photograph: An Archive of Mobility between South Africa and India
Authors: Dhupelia-Mesthrie Uma
Published: September 2011

Inspired by recent scholarship that calls for a more critical engagement with archives and knowledge production, this article plots the biography of an archive in Cape Town. Unravelling the layers of paperwork, it locates the origins of the archive in a repressive state project of excluding Indian immigrants and controlling those within the borders of the Cape Colony. The paper trail reveals documents of identity and the state’s attempts to verify identity. In seeking to answer the question as to how the historian should approach such an archive of control and surveillance, it concludes that a social history and gendered approach to migration is possible and the real treasures are those documents that enter the archive beyond the limits of state intentions.
Predictors of Surgical Outcomes of Uvulopalatopharyngoplasty for Obstructive Sleep Apnea Hypopnea Syndrome
Authors: Xiong Yuan Ping , Yi Hong Liang , Yin Shan Kai , Meng Li Li , Tang Xu Lan , Guan Jian , Luo Hui Ping , Zhang Wei Tian , Chen Bin
Published: September 2011

Objectives

To investigate predictors of surgical outcomes of uvulopalatopharyngoplasty (UPPP) for obstructive sleep apnea hypopnea syndrome (OSAHS).

Study Design

Case series with planned data collection.

Setting

A university medical center.

Subjects and Methods

Thirty‐nine patients with OSAHS received Z‐palatopharyngoplasty (ZPPP) or Han‐uvulopalatopharyngoplasty (H‐UPPP). All patients were evaluated within 3 months before surgery and at 6 to 12 months after surgery. Statistical analyses were conducted on preoperative parameters that could have affected surgical efficacy and outcome. Success was defined as an apnea–hypopnea index (AHI) fewer than 20 times per hour and a decrease of more than 50%.

Results

The success rate was 56.4% (22/39 patients). There were statistically significant differences in AHI, lowest oxygen saturation (L‐Sao2), time with oxygen saturation less than 90% (CT90), percentage of time with oxygen saturation less than 90% (CT90%), microarousal index (MI), apolipoprotein E (ApoE), high‐density lipoprotein (HDL), fasting blood glucose (FBG), and Friedman OSA stage between the treatment success and failure groups. Higher success rate was predicted by lower severity, as indicated by lower AHI, CT90, CT90%, and MI; higher L‐Sao2; and fewer glucose and lipid metabolism abnormalities, shown by lower ApoE and FBG and higher HDL.

Conclusions

Disease severity, glucose and lipid metabolism, and Friedman OSA stage may be important predictors of surgical outcome of UPPP for OSAHS.
T1‐T2 Squamous Cell Carcinoma of the Uvula
Authors: Espinosa Restrepo Federico , Martínez Capoccioni Gabriel , Martín Martín Carlos
Published: September 2011

Objective

No specific epidemiology data are available for carcinoma of the uvula. This study aims to analyze the epidemiological characteristics and treatment outcomes of carcinoma of the uvula at the authors’ institution.

Study Design

Case series with chart review.

Setting

Service of ENT–Head and Neck Surgery, University Hospital Complex of Santiago de Compostela (CHUS), Spain.

Subjects and Methods

Retrospective epidemiological study of 21 male patients, mean age 57.52 years, diagnosed with squamous cell carcinoma of the uvula in the CHUS between January 1990 and June 2009.

Results

Most patients presented with odynophagia and exophytic lesions microscopically consistent with moderately differentiated squamous cell carcinoma. Despite the size of the lesions (T1 and T2), more than half of the patients had lymph node metastases at diagnosis. More than 90.0% of patients with lesions larger than 1 cm presented with lymph node metastases. Although more than 70.0% of patients underwent a neck dissection in the first year after diagnosis, only 25.0% were free of metastatic disease. Recurrences occurred at a mean of 14 months from baseline in more than 50.0% of cases. Of the patients, 52.4% died, with a median survival of 38.15 months after diagnosis. The overall 5‐year survival was 39.0%. According to tumor size, 5‐year survival was 53.0% for T1 and 27.0% for T2.

Conclusion

According to the data, clinical features of carcinoma of the uvula correspond with aggressive tumors, with rapid onset and a major negative impact regardless of tumor size at diagnosis. Early stage patients benefit significantly from surgical treatments with neck dissections.