bluuebunny/crossref_metadata_2025 huggingface dataset:
On the Discovery, Biological Effects, and Use of Cisplatin and Metallocenes in Anticancer Chemotherapy
Authors: Gómez-Ruiz Santiago , Maksimović-Ivanić Danijela , Mijatović Sanja , Kaluđerović Goran N.
Published: July 2012

The purpose of this paper is to summarize mode of action of cisplatin on the tumor cells, a brief outlook on the metallocene compounds as antitumor drugs as well as the future tendencies for the use of the latter in anticancer chemotherapy. Molecular mechanisms of cisplatin interaction with DNA, DNA repair mechanisms, and cellular proteins are discussed. Molecular background of the sensitivity and resistance to cisplatin, as well as its influence on the efficacy of the antitumor immune response was evaluated. Furthermore, herein are summarized some metallocenes (titanocene, vanadocene, molybdocene, ferrocene, and zirconocene) with high antitumor activity.
Application of FT‐IR Spectroscopy for Fingerprinting of Zymomonas mobilis Respiratory Mutants
Authors: Grube M. , Rutkis R. , Gavare M. , Lasa Z. , Strazdina I. , Galinina N. , Kalnenieks U.
Published: July 2012

Z. mobilis ATCC 29191 and its respiratory knockout mutants, kat-, ndh-, cytB-, and cydB-, were grown under anaerobic and aerobic conditions. FT‐IR spectroscopy was used to study the variations of the cell macromolecular composition. Quantitative analysis showed that the concentration ratios—nucleic acids to lipids, for Z. mobilis parent strain, kat-, ndh-, cytB-, and cydB- strains, clearly distinguished Z. mobilis parent strain from its mutant derivatives and corresponded fairly well to the expected degree of biochemical similarity between the strains. Two different FT‐IR‐spectra hierarchical cluster analysis (HCA) methods were created to differentiate Z. mobilis parent strain and respiratory knockout mutant strains. HCA based on discriminative spectra ranges of carbohydrates, nucleic acids, and lipids allowed to evaluate the influence of growth environment (aeration, growth phase) on the macromolecular composition of cells and differentiate the strains. HCA based on IR spectra of inoculums, in a diagnostic region including the characteristic nucleic acid vibration modes, clearly discriminated the strains under study. Thus it was shown that FT‐IR spectroscopy can distinguish various alterations of Z. mobilis respiratory metabolism by HCA of biomass spectra.
Molecular and Cellular Alterations in Down Syndrome: Toward the Identification of Targets for Therapeutics
Authors: Créau Nicole
Published: July 2012

Down syndrome is a complex disease that has challenged molecular and cellular research for more than 50 years. Understanding the molecular bases of morphological, cellular, and functional alterations resulting from the presence of an additional complete chromosome 21 would aid in targeting specific genes and pathways for rescuing some phenotypes. Recently, progress has been made by characterization of brain alterations in mouse models of Down syndrome. This review will highlight the main molecular and cellular findings recently described for these models, particularly with respect to their relationship to Down syndrome phenotypes.
2D MR Spectroscopy Combined with Prior-Knowledge Fitting Is Sensitive to HCV-Associated Cerebral Metabolic Abnormalities
Authors: Nagarajan Rajakumar , Sarma Manoj K. , Thames April D. , Castellon Steven A. , Hinkin Charles H. , Thomas M. Albert
Published: July 2012

There is an evidence of neurocognitive dysfunction even in the absence of advanced liver disease in chronic hepatitis C virus (HCV) infection. Brain metabolism has been investigated non-invasively using one-dimensional (1D)in vivoMagnetic Resonance Spectroscopy (MRS) over three decades. Even though highly concentrated cerebral metabolites (N-acetylaspartate, creatine, choline, glutamate/glutamine, myo-inositol) have been detected using MRS, other metabolites at low concentrations (~1–3 mM or less) including glutathione, aspartate and GABA are quite difficult to observe using 1D MRS. In order to resolve overlapping resonances from a number of metabolites, a remedy is to add a second spectral dimension to the existing 1D MRS. Localized two-dimensional correlated spectroscopy (L-COSY) has been developed over the last decade to enhance the spectral dispersion by using the second spectral dimension. We have evaluated this L-COSY technique in the frontal white/gray matter regions of 14 HCV+ (mean age of 56.2 years) and 14 HCV− (mean age of 46.6 years) subjects. Our preliminary results showed significantly increased myo-inositol and glutathione in the HCV+ compared to the HCV− subjects. Hence, glutathione and myo-inositol should be considered along with other metabolites as important markers of inflammation.
DCDR Spectroscopy as Efficient Tool for Liposome Studies: Aspect of Preparation Procedure Parameters
Authors: Kočišová E. , Vodáková A. , Procházka M.
Published: July 2012

Drop‐coating deposition Raman (DCDR) spectroscopy was employed to study liposome suspensions. The method is based on a specific drying process on the hydrophobic surface that efficiently accumulates the macromolecular sample in a ring of the edge of the dried drop. We studied liposome suspensions purchased from two sources (Avanti Polar Lipids, Inc. and Sigma‐Aldrich, Co.) and prepared under different conditions. Structure of the dried drop substantially depends on the lipid concentration, lipid composition of the sample, and used solvent. Optimal lipid concentration is about 0.3 mg/ml in all cases, asolectin and DSPC suspensions form compact dried drops when dissolved in water and phosphate buffer, respectively. Drying process of the sample drop does not influence the initial phase state (gel or liquid‐crystalline) of the studied liposomes excepting DSPC from Sigma‐Aldrich, Co.
Pt(II) Complexes with Linear Diamines—Part I: Vibrational Study of Pt‐Diaminopropane
Authors: de Carvalho Ana L. M. Batista , Fiuza Sónia M. , Tomkinson John , de Carvalho Luís A. E. Batista , Marques M. Paula M.
Published: July 2012

A conformational analysis of the Pt(dap)Cl2 complex (dap = 1, 3‐diaminopropane) was performed by vibrational spectroscopy (FTIR, Raman, and INS), coupled to quantum mechanical methods within the density functional theory (DFT) and effective core potential (ECP) approaches. A complete spectral assignment of the system was achieved, due to the combined use of all available vibrational spectroscopic techniques. A good agreement was found between experimental and theoretical results, as well as with reported data for analogous complexes (e.g., cisplatin).
Existence Theorem for Integral and Functional Integral Equations with Discontinuous Kernels
Authors: Hassan Ezzat R.
Published: July 2012

Existence of extremal solutions of nonlinear discontinuous integral equations of
Volterra type is proved. This result is extended herein to functional Volterra integral equations
(FVIEs) and to a system of discontinuous VIEs as well.
EPR and FTIR Spectroscopies Study of Human Blood after Irradiation
Authors: Polakovs M. , Mironova-Ulmane N. , Pavlenko A. , Reinholds E. , Gavare M. , Grube M.
Published: July 2012

In the present work we report results of investigations of human blood before and after radioisotope Tc99m diagnosis by electron paramagnetic resonance (EPR) and Fourier transform infrared (FTIR) spectroscopies. It is shown that EPR can detect the concentration of methaemoglobin and transferrin ions more accurately than any other technique. FTIR spectra indicated that radiation caused conformational and concentration changes of proteins. Hierarchical cluster analysis (HCA) was created as time‐saving tool for discrimination of initial and irradiated in vivo human blood samples.
Neutrophil Reverse Migration Becomes Transparent with Zebrafish
Authors: Starnes Taylor W. , Huttenlocher Anna
Published: July 2012

The precise control of neutrophil-mediated inflammation is critical for both host defense and the prevention of immunopathology. In vivo imaging studies in zebrafish, and more recently in mice, have made the novel observation that neutrophils leave a site of inflammation through a process called neutrophil reverse migration. The application of advanced imaging techniques to the genetically tractable, optically transparent zebrafish larvae was critical for these advances. Still, the mechanisms underlying neutrophil reverse migration and its effects on the resolution or priming of immune responses remain unclear. Here, we review the current knowledge of neutrophil reverse migration, its potential roles in host immunity, and the live imaging tools that make zebrafish a valuable model for increasing our knowledge of neutrophil behavior in vivo.
Retrospective Case-Control Study of Apolipoprotein J/Clusterin Protein Expression in Early Liveborn Neonatal Deaths with and without Pontosubicular Necrosis
Authors: Kurian Kathreena M. , McGuone Declan
Published: July 2012

Aims. Our objective was to examine Apo J protein expression in a total of 27 early liveborn neonatal deaths (less than 7 days of age) selected from the Scottish Perinatal Study (gestation of 25–42 weeks) comparing a group with histological pontosubicular necrosis (PSN) () to a control group lacking PSN ().Methods. Using immunohistochemistry we evaluated postmortem pons and hippocampus from patients with PSN versus controls.Results. In the group with PSN, 11/12 (92%) cases showed positive Apo J neurones in the hippocampus/pons compared with 6/15 (40%) cases without PSN (, odds ratio 27.5, 95% confidence interval 2.881–262.48, using exact logistic regression)—independent of gestation, presence or absence of clinical asphyxia, duration of labour, or postnatal age. Clinical asphyxia was present in 10/15 (67%) without PSN compared with 11/12 (92%) with PSN. Neuronal Apo J positivity was present in 15/21 (71%) of clinically asphyxiated cases compared with 2/6 (33%) of the cases with no evidence of clinical asphyxia (, odds ratio 5, 95% confidence interval 0.71 to 34.94).Conclusions. Apo J neuronal protein expression is significantly increased in cases with PSN compared to cases without PSN—independent of gestation, presence of clinical asphyxia, duration of labour, or postnatal age.
Formation of Mesoporous Materials from Silica Dissolved in Various NaOH Concentrations: Effect of pH and Ionic Strength
Authors: Park Jayhyun , Han Yosep , Kim Hyunjung
Published: July 2012

We describe the effects of NaOH/SiO2 ratio and pH on the formation of mesoporous materials, which was synthesized via an alkali‐metal hydroxide fusion method, from amorphous silica dissolved in NaOH. Physical properties (e.g., specific surface area, pore volume, and pore size) of mesoporous materials synthesized at different conditions (i.e., pH, NaOH/SiO2 ratio) were evaluated through X‐ray diffraction, nitrogen adsorption‐desorption, and transmission electron microscope analyses. The results showed that, at the NaOH/SiO2 ratios of 0.5, 1, and 2, gels were successfully synthesized while no product was formed at the NaOH/SiO2 ratios greater than 2. Additionally, mesoporous materials were found to be formed at both pH 10 and 11 while they were unstable under more alkaline conditions. The adsorption/desorption isotherm results for the mesoporous materials synthesized at around pH 11 and with NaOH/SiO2 ratios of 0.5–0.8 showed a hysteresis loop characteristic of the bottle‐neck pore shape. Furthermore, mesoporous materials with good physical properties were synthesized from all gels at pH 10 regardless of sodium concentration.
A Comparison between Vanadyl, Vanadate, and Decavanadate Effects in Actin Structure and Function: Combination of Several Spectroscopic Studies
Authors: Ramos S. , Moura J. J. G. , Aureliano M.
Published: July 2012

The studies about the interaction of actin with vanadium are seldom. In the present paper the effects of vanadyl, vanadate, and decavanadate in the actin structure and function were compared. Decavanadate clearly interacts with actin, as shown by  51V‐NMR spectroscopy. Decavanadate interaction with actin induces protein cysteine oxidation and vanadyl formation, being both prevented by the natural ligand of the protein, ATP. Monomeric actin (G‐actin) titration with vanadyl, as analysed by EPR spectroscopy, indicates a 1 : 1 binding stoichiometry and a kd of 7.5 μM. Both decavanadate and vanadyl inhibited G‐actin polymerization into actin filaments (F‐actin), with a IC50 of 68 and 300 μM, respectively, as analysed by light‐scattering assays. However, only vanadyl induces G‐actin intrinsic fluorescence quenching, which suggests the presence of vanadyl high‐affinity actin‐binding sites. Decavanadate increases (2.6‐fold) actin hydrophobic surface, evaluated using the ANSA probe, whereas vanadyl decreases it (15%). Finally, both vanadium species increased ε‐ATP exchange rate (k = 6.5 × 10−3 and 4.47 × 10−3 s−1 for decavanadate and vanadyl, resp.). Putting it all together, it is suggested that actin, which is involved in many cellular processes, might be a potential target not only for decavanadate but above all for vanadyl.
A Note on the Right‐Hand Side Identification Problem Arising in Biofluid Mechanics
Authors: Erdogan Abdullah Said
Published: July 2012

The inverse problem of reconstructing the right‐hand side (RHS) of a mixed problem for one‐dimensional diffusion equation with variable space operator is considered. The well‐posedness of this problem in Hölder spaces is established.
New Theories on Boundary Layer Transition and Turbulence Formation
Authors: Liu Chaoqun , Lu Ping , Chen Lin , Yan Yonghua
Published: July 2012

This paper is a short review of our recent DNS work on physics of late boundary layer transition and turbulence. Based on our DNS observation, we propose a new theory on boundary layer transition, which has five steps, that is, receptivity, linear instability, large vortex structure formation, small length scale generation, loss of symmetry and randomization to turbulence. For turbulence generation and sustenance, the classical theory, described with Richardson's energy cascade and Kolmogorov length scale, is not observed by our DNS. We proposed a new theory on turbulence generation that all small length scales are generated by “shear layer instability” through multiple level ejections and sweeps and consequent multiple level positive and negative spikes, but not by “vortex breakdown.” We believe “shear layer instability” is the “mother of turbulence.” The energy transferring from large vortices to small vortices is carried out by multiple level sweeps, but does not follow Kolmogorov's theory that large vortices pass energy to small ones through vortex stretch and breakdown. The loss of symmetry starts from the second level ring cycle in the middle of the flow field and spreads to the bottom of the boundary layer and then the whole flow field.
Degradation of Antibiotics in Wastewater during Sonolysis, Ozonation, and Their Simultaneous Application: Operating Conditions Effects and Processes Evaluation
Authors: Naddeo Vincenzo , Ricco Daniele , Scannapieco Davide , Belgiorno Vincenzo
Published: July 2012

Pharmaceutical drugs frequently found in treated effluents, lakes and rivers, can exhibit adverse effects on aquatic organisms. The present study focuses on the application of advanced oxidation processes as ozonation (O3), sonolysis (US), and their combined application (US+O3) for the degradation of diclofenac in wastewater. Under the applied conditions, all three systems proved to be able to induce diclofenac oxidation, leading to 22% of mineralization for O3and 36% for US process after 40 min of treatment. The synergy observed in the combined schemes, mainly due to the effects of US in enhancing the O3decomposition, led to a higher mineralization (about 40%) for 40-minute treatment and to a significantly higher mineralization level for shorter treatment duration.
Brillouin Neutron Spectroscopy as a Probe to Investigate Collective Density Fluctuations in Biomolecules Hydration Water
Authors: Russo D. , Orecchini A. , De Francesco A. , Formisano F. , Laloni A. , Petrillo C. , Sacchetti F.
Published: July 2012

The role of water in the behaviour of biomolecules is well recognized. The coupling of motions between water and biomolecules has been studied in a wide time scale for the self part while collective dynamics is still quite unexplored. Self‐dynamics provides information about the diffusion processes of water molecules and relaxation processes of the protein structure. Collective density fluctuations might provide important insight on the transmission of information possibly correlated to biological functionality. The idea that hydration water layers surrounding a biological molecule show a self‐dynamical signature that differs appreciably from that of bulk water, in analogy with glass‐former systems, is quite accepted. In the same picture Brillouin terahertz spectroscopy has been used to directly probe collective dynamics of hydration water molecules around biosystems, showing a weaker coupling and a more bulklike behaviour. We will discuss results of collective modes of hydration water, arising from neutron Brillouin spectroscopy, in the context of biomolecules‐solvent interaction.
Pulmonary Metastasis from Pseudomyxoma Peritonei
Authors: Kitai Toshiyuki
Published: July 2012

Pseudomyxoma peritonei (PMP) is a rare clinical condition, where copious mucinous ascites accumulate in the peritoneal cavity due to dissemination of mucin-producing tumor. Because of this disseminating, yet nonmetastasizing, behavior, PMP attracts much interest from surgical oncologists in that aggressive locoregional therapy can give the opportunity of long survival and even cure. Although extra-abdominal metastasis is exceptionally rare, the lung is the most likely site in such a case. In this paper, the clinical findings and treatment of eleven cases with pulmonary metastasis from PMP were reviewed, including ten cases in the literature and one case which we experienced. The clinical features of PMP cases with pulmonary metastasis were similar to cases without pulmonary metastasis. The histological type was low-grade mucinous neoplasm in most cases. Pulmonary lesions were resected in seven cases in which abdominal lesions were controlled by cytoreductive surgery and hyperthermic intraperitoneal chemotherapy or another therapeutic modality. Disease-free state was maintained in five cases at the end of the follow-up period. However, it should be noted that rapid progression after resection was seen in two cases, suggesting that biological features may have changed by surgical intervention.
Comparison of Synthesis Strategies for a Dual-Polarized Reflectarray
Authors: Marnat Loic , Loison Renaud , Gillard Raphaël , Bresciani Daniele , Legay Hervé
Published: July 2012

This paper presents and compares four optimization strategies for printed reflectarrays. They are applied to synthesize a dual-polarized reflectarray using two kinds of slot-loaded patches. They provide objective criteria to deal with the numerous geometrical parameters available to tune the phase. The study relies on the comparative measurements of four different prototypes for the same reflectarray (with the wavelength at  GHz).
Reversion of P-Glycoprotein-Mediated Multidrug Resistance in Human Leukemic Cell Line by Diallyl Trisulfide
Authors: Xia Qing , Wang Zhi-Yong , Li Hui-Qing , Diao Yu-Tao , Li Xiao-Li , Cui Jia , Chen Xue-Liang , Li Hao
Published: July 2012

Multidrug resistance (MDR) is the major obstacle in chemotherapy, which involves multiple signaling pathways. Diallyl trisulfide (DATS) is the main sulfuric compound in garlic. In the present study, we aimed to explore whether DATS could overcome P-glycoprotein-(P-gp-)mediated MDR in K562/A02 cells, and to investigate whether NF-κB suppression is involved in DATS-induced reversal of MDR. MTT assay revealed that cotreatment with DATS increased the response of K562/A02 cells to adriamycin (the resistance reversal fold was 3.79) without toxic side effects. DATS could enhance the intracellular concentration of adriamycin by inhibiting the function and expression of P-gp, as shown by flow cytometry, RT-PCR, and western blot. In addition, DATS resulted in more K562/A02 cell apoptosis, accompanied by increased expression of caspase-3. The expression of NF-κB/p65 (downregulation) was significantly linked to the drug-resistance mechanism of DATS, whereas the expression of IκBαwas not affected by DATS. Our findings demonstrated that DATS can serve as a novel, nontoxic modulator of MDR, and can reverse the MDR of K562/A02 cells in vitro by increasing intracellular adriamycin concentration and inducing apoptosis. More importantly, we proved for the first time that the suppression of NF-κB possibly involves the molecular mechanism in the course of reversion by DATS.
Surface Layer Properties after Successive EDM or EDA and Then Superficial Roto-Peen Machining
Authors: Dmowska Agnieszka , Nowicki Bogdan , Podolak-Lejtas Anna
Published: July 2012

The paper presents the results of the influence of basic electrical discharge machining EDM parameters and electrical discharge alloying EDA parameters on surface layer properties and on selected performance properties of machine parts after such machining but also the influence of superficial cold-work treatment applied after the EDM of EDA on modification of these properties. The investigations included texture of the surface, metallographic microstructure, microhardness distribution, fatigue strength, and resistance to abrasive wear. It was proved that the application of the roto-peen after the EDM and the EDA resulted in lowering roughness height up to 70%, the elevation of surface layer microhardness by 300–700 μHV, and wear resistance uplifting by 300%.
Raman Microspectroscopy of the Yeast Vacuoles
Authors: Bednárová Lucie , Palacký Jan , Bauerová Václava , Hrušková-Heidingsfeldová Olga , Pichová Iva , Mojzeš Peter
Published: July 2012

In the present work, real ability of a confocal Raman microspectroscopy to monitor chemical composition of the vacuoles within living yeast cells was investigated and critically assessed. Simple, economical, and practical protocols of the yeast immobilization suitable for less laborious, high‐throughput, and spatially resolved Raman measurements were tested for their possible impacts on physiological states and viability of the cells. We have demonstrated that, acquiring Raman spectra from statistically sound sets of immobilized cells and employing advanced multivariate methods for spectral analysis, the chemical composition of the yeast vacuoles can be reliably studied. The most easily and accurately quantifiable seems to be the concentration of polyphosphates which can be unambiguously identified due to unmistakable Raman features. Our approach can be useful for routine, label‐free, and noninvasive monitoring of the chemical composition of the vacuoles of living yeasts exposed to various stress factors, the information important in biomedical research of pathogens.
Epileptic Encephalopathy in Children with Risk Factors for Brain Damage
Authors: Ricardo-Garcell Josefina , Harmony Thalía , Porras-Kattz Eneida , Colmenero-Batallán Miguel J. , Barrera-Reséndiz Jesús E. , Fernández-Bouzas Antonio , Cruz-Rivero Erika
Published: July 2012

In the study of 887 new born infants with prenatal and perinatal risk factors for brain damage, 11 children with West syndrome that progressed into Lennox-Gastaut syndrome and another 4 children with Lennox-Gastaut syndrome that had not been preceded by West syndrome were found. In this study we present the main findings of these 15 subjects. In all infants multifactor antecedents were detected. The most frequent risk factors were prematurity and severe asphyxia; however placenta disorders, sepsis, and hyperbilirubinemia were also frequent. In all infants MRI direct or secondary features of periventricular leukomalacia were observed. Followup of all infants showed moderate to severe neurodevelopmental delay as well as cerebral palsy. It is concluded that prenatal and perinatal risk factors for brain damage are very important antecedents that should be taken into account to follow up those infants from an early age in order to detect and treat as early as possible an epileptic encephalopathy.
Highlights for the Management of a Child with Proteinuria and Hematuria
Authors: Gattineni Jyothsna
Published: July 2012

The identification of hematuria or proteinuria in an otherwise healthy child can cause anxiety to both the family and the pediatrician. The etiology of hematuria and proteinuria includes a long list of conditions, and detailed workup can be exhaustive, expensive and not essential in most of the patients. As will be described in this paper, most of the children with proteinuria or hematuria have a benign etiology. The primary role of the pediatrician is to identify hematuria/proteinuria, recognize the common causes of hematuria/proteinuria, and more importantly identify children with serious conditions that need referral to the nephrologist in a timely manner.
Phylogenetic Position of Aquificales Based on the Whole Genome Sequences of Six Aquificales Species
Authors: Oshima Kenro , Chiba Yoko , Igarashi Yasuo , Arai Hiroyuki , Ishii Masaharu
Published: July 2012

Species belonging to the order Aquificales are believed to be an early branching lineage within the Bacteria. However, the branching order of this group in single-gene phylogenetic trees is highly variable; for example, it has also been proposed that the Aquificales should be grouped with ε-proteobacteria. To investigate the phylogenetic position of Aquificales at the whole-genome level, here we reconstructed the phylogenetic trees of 18 bacteria including six Aquificales species based on the concatenated data of proteins shared by these bacteria. In the phylogenetic tree based on the whole-genome information, Aquificales was more closely related to Thermotogales than to Proteobacteria, suggesting that the Aquificales is a relatively early branching lineage within the Bacteria. Moreover, we classified the phylogenetic tree of each conserved orthologous protein by its topology. As a result, in the most major type of the phylogenetic trees, Aquificales was closely related to the Thermotogales. However, Aquificales was closely related to ε-proteobacteria in 21.0% of all phylogenetic trees, suggesting that many proteins phylogenetically related to the ε-proteobacteria may be encoded in the genomes of the members of the Aquificales. This unique feature may be responsible for the high variability in the branching order of Aquificales in single-gene phylogenetic trees.
Selection of Spatiotemporal Features in Breast MRI to Differentiate between Malignant and Benign Small Lesions Using Computer-Aided Diagnosis
Authors: Steinbruecker F. , Meyer-Baese A. , Plant C. , Schlossbauer T. , Meyer-Baese U.
Published: July 2012

Automated detection and diagnosis of small lesions in breast MRI represents a challenge for the traditional computer-aided diagnosis (CAD) systems. The goal of the present research was to compare and determine the optimal feature sets describing the morphology and the enhancement kinetic features for a set of small lesions and to determine their diagnostic performance. For each of the small lesions, we extracted morphological and dynamical features describing both global and local shape, and kinetics behavior. In this paper, we compare the performance of each extracted feature set for the differential diagnosis of enhancing lesions in breast MRI. Based on several simulation results, we determined the optimal feature number and tested different classification techniques. The results suggest that the computerized analysis system based on spatiotemporal features has the potential to increase the diagnostic accuracy of MRI mammography for small lesions and can be used as a basis for computer-aided diagnosis of breast cancer with MR mammography.
Autoantibodies in Autoimmune Pancreatitis
Authors: Smyk Daniel S. , Rigopoulou Eirini I. , Koutsoumpas Andreas L. , Kriese Stephen , Burroughs Andrew K. , Bogdanos Dimitrios P.
Published: July 2012

Autoimmune pancreatitis (AIP) was first used to describe cases of pancreatitis with narrowing of the pancreatic duct, enlargement of the pancreas, hyper-γ-globulinaemia, and antinuclear antibody (ANA) positivity serologically. The main differential diagnosis, is pancreatic cancer, which can be ruled out through radiological, serological, and histological investigations. The targets of ANA in patients with autoimmune pancreatitis do not appear to be similar to those found in other rheumatological diseases, as dsDNA, SS-A, and SS-B are not frequently recognized by AIP-related ANA. Other disease-specific autoantibodies, such as, antimitochondrial, antineutrophil cytoplasmic antibodies or diabetes-specific autoantibodies are virtually absent. Further studies have focused on the identification of pancreas-specific autoantigens and reported significant reactivity to lactoferrin, carbonic anhydrase, pancreas secretory trypsin inhibitor, amylase-alpha, heat-shock protein, and plasminogen-binding protein. This paper discusses the findings of these investigations and their relevance to the diagnosis, management, and pathogenesis of autoimmune pancreatitis.
Foraging Activity and Trophic Spectrum of Red AntPogonomyrmex barbatusSmith, 1858, in Productivity-Contrasted Microenvironments
Authors: Guzmán-Mendoza Rafael , Castaño-Meneses Gabriela , Zavala-Hurtado José Alejandro
Published: July 2012

Foraging strategies can be influenced by many factors such as abundance, availability, and toxicity of the resources. In arid zones, the distribution and productivity of plants also act as additional factors that affect foraging strategies. Twenty colonies ofPogonomyrmex barbatusants were studied in an arid zone of central Mexico to evaluate the trophic niche breadth in two sites with contrasting productivities in terms of their diversity and amount of resources during two seasons. The results suggest that when the resources are abundant as in the rainy season, the trophic niche breadth is reduced in sites with high productivity and, in the same sites, the trophic niche breadth increases when the resources are limited as in the dry season. In contrast, the trophic niche breadth is similar in both conditions of resource availability (i.e., rainy and dry seasons) at sites with low productivity. During the dry season, populations ofP. barbatusshowed a similar foraging behavior in sites with high and low productivity. Thus, the particular characteristics of a site can significantly affect the foraging strategies of the ants in those environments.
Endothelin-B Receptors and Left Ventricular Dysfunction after Regional versus Global Ischaemia-Reperfusion in Rat Hearts
Authors: Bibli Sofia-Iris , Toli Eleni V. , Vilaeti Agapi D. , Varnavas Varnavas C. , Baltogiannis Giannis G. , Papalois Apostolos , Kyriakides Zenon S. , Kolettis Theofilos M.
Published: July 2012

Background. Endothelin-1 (ET-1) is implicated in left ventricular dysfunction after ischaemia-reperfusion. ETA and ETB receptors mediate diverse actions, but it is unknown whether these actions depend on ischaemia type and duration. We investigated the role of ETB receptors after four ischaemia-reperfusion protocols in isolated rat hearts.Methods. Left ventricular haemodynamic variables were measured in the Langendorff-perfused model after 40- and 20-minute regional or global ischaemia, followed by 30-minute reperfusion. Wild-type (n=39) and ETB-deficient (n=41) rats were compared. Infarct size was measured using fluorescent microspheres after regional ischaemia-reperfusion.Results. Left ventricular dysfunction was more prominent in ETB-deficient rats, particularly after regional ischaemia. Infarct size was smaller (P=0.006) in wild-type (31.5±4.4%) than ETB-deficient (45.0±7.3%) rats after 40 minutes of regional ischaemia-reperfusion. Although the recovery of left ventricular function was poorer after 40-minute ischaemia-reperfusion, end-diastolic pressure in ETB-deficient rats was higher after 20 than after 40 minutes of regional ischaemia-reperfusion.Conclusion. ETB receptors exert cytoprotective effects in the rat heart, mainly after regional ischaemia-reperfusion. Longer periods of ischaemia suppress the recovery of left ventricular function after reperfusion, but the role of ETB receptors may be more important during the early phases.
CXCR3+ T Regulatory Cells Selectively Accumulate in Human Ovarian Carcinomas to Limit Type I Immunity
Authors: Redjimi Nassima , Raffin Caroline , Raimbaud Isabelle , Pignon Pascale , Matsuzaki Junko , Odunsi Kunle , Valmori Danila , Ayyoub Maha
Published: July 2012

Antitumor type I T-cell responses involving IFN-γ production are critical to control cancer, but the efficacy of this response is limited by a variety of immunosuppressive mechanisms that promote tumoral immune escape. One critical mechanism involves the accumulation of FOXP3+ T regulatory cells (Treg), a class of suppressive T cells that prevent excessive tissue destruction caused by unchecked immune responses. Recent studies have revealed that FOXP3+ Treg include distinct subsets specifically controlling over the corresponding effector subset. In particular, CXCR3+ Treg have been described as a subset specialized in the control of type I T-cell responses in vivo. Here, we show that CXCR3+ Treg are highly enriched in human ovarian carcinomas, particularly in solid tumor masses, where they represent the majority of Treg. Tumor-associated CXCR3+. Treg coexpress T-bet but do not secrete IFN-γ ex vivo and suppress proliferation and IFN-γ secretion of T effectors. In addition, they coexpress Helios, suggesting that they originate from natural Treg. Finally, we show that the proportion of CXCR3+ Treg at tumor sites is directly correlated with that of CXCR3+ T effectors, consistent with expression of CXCR3 ligands. Together, our findings support the concept that natural CXCR3+ T-bet+ Treg selectively accumulate in ovarian tumors to control type I T-cell responses, resulting in the collateral limitation of efficient antitumor immunity. Cancer Res; 72(17); 4351–60. ©2012 AACR.
Dual Targeting of the Cyclin/Rb/E2F and Mitochondrial Pathways in Mantle Cell Lymphoma with the Translation Inhibitor Silvestrol
Authors: Alinari Lapo , Prince Courtney J. , Edwards Ryan B. , Towns William H. , Mani Rajeswaran , Lehman Amy , Zhang Xiaoli , Jarjoura David , Pan Li , Kinghorn A. Douglas , Grever Michael R. , Baiocchi Robert A. , Lucas David M.
Published: July 2012

Purpose: During cell-cycle progression, D-cyclins activate cyclin-dependent kinases (CDKs) 4/6 to inactivate Rb, permitting E2F1-mediated S-phase gene transcription. This critical pathway is typically deregulated in cancer, and novel inhibitory strategies would be effective in a variety of tumors. The protein synthesis inhibitor silvestrol has potent activity in B-cell leukemias via the mitochondrial pathway of apoptosis, and also reduces cyclin D1 expression in breast cancer and lymphoma cell lines. We hypothesized that this dual activity of silvestrol would make it especially effective in malignancies driven by aberrant cyclin D1 expression.

Experimental Design: Mantle cell lymphoma (MCL), characterized by elevated cyclin D1, was used as a model to test this approach. The cyclin D/Rb/E2F1 pathway was investigated in vitro using MCL cell lines and primary tumor cells. Silvestrol was also evaluated in vivo using an aggressive model of MCL.

Results: Silvestrol showed low nanomolar potency both in MCL cell lines and primary MCL tumor cells. D-cyclins were depleted with just 10 nmol/L silvestrol at 16 hours, with subsequent reductions of phosphorylated Rb, E2F1 protein, and E2F1 target transcription. As showed in other leukemias, silvestrol caused Mcl-1 depletion followed by mitochondrial depolarization and caspase-dependent apoptosis, effects not related to inhibition of CDK4/6. Silvestrol significantly (P < 0.0001) prolonged survival in a MCL xenograft model without detectable toxicity.

Conclusions: These data indicate that silvestrol effectively targets the cyclin/CDK/Rb pathway, and additionally induces cytotoxicity via intrinsic apoptosis. This dual activity may be an effective therapeutic strategy in MCL and other malignancies. Clin Cancer Res; 18(17); 4600–11. ©2012 AACR.
Systematic Kinome shRNA Screening Identifies CDK11 (PITSLRE) Kinase Expression Is Critical for Osteosarcoma Cell Growth and Proliferation
Authors: Duan Zhenfeng , Zhang Jianming , Choy Edwin , Harmon David , Liu Xianzhe , Nielsen Petur , Mankin Henry , Gray Nathanael S. , Hornicek Francis J.
Published: July 2012

Purpose: Identification of new targeted therapies is critical to improving the survival rate of patients with osteosarcoma. The goal of this study is to identify kinase based potential therapeutic target in osteosarcomas.

Experimental Design: We used a lentiviral-based shRNA kinase library to screen for kinases which play a role in osteosarcoma cell survival. The cell proliferation assay was used to evaluate cell growth and survival. siRNA assays were applied to confirm the observed phenotypic changes resulting from the loss of kinase gene expression. CDK11 (PITSLRE) was identified as essential for the survival of osteosarcoma cells, and its expression was confirmed by Western blot analysis and immunohistochemistry. Overall patient survival was correlated with the CDK11 expression and its prognosis. The role of CDK11 expression in sustaining osteosarcoma growth was further evaluated in an osteosarcoma xenograft model in vivo.

Results: Osteosarcoma cells display high levels of CDK11 expression. CDK11 expression knocked down by either lentiviral shRNA or siRNA inhibit cell growth and induce apoptosis in osteosarcoma cells. Immunohistochemical analysis showed that patients with osteosarcoma with high CDK11 tumor expression levels were associated with significantly shorter survival than patients with osteosarcoma with low level of tumor CDK11 expression. Systemic in vivo administration of in vivo ready siRNA of CDK11 reduced the tumor growth in an osteosarcoma subcutaneous xenograft model.

Conclusions: We show that CDK11 signaling is essential in osteosarcoma cell growth and survival, further elucidating the regulatory mechanisms controlling the expression of CDK11 and ultimately develop a CDK11 inhibitor that may provide therapeutic benefit against osteosarcoma. Clin Cancer Res; 18(17); 4580–8. ©2012 AACR.
Group I p21-Activated Kinases (PAKs) Promote Tumor Cell Proliferation and Survival through the AKT1 and Raf–MAPK Pathways
Authors: Menges Craig W. , Sementino Eleonora , Talarchek Jacqueline , Xu Jinfei , Chernoff Jonathan , Peterson Jeffrey R. , Testa Joseph R.
Published: July 2012

Group I p21–activated kinases (PAK) are important effectors of the small GTPases Rac and Cdc42, which regulate cell motility/migration, survival, proliferation, and gene transcription. Hyperactivation of these kinases have been reported in many tumor types, making PAKs attractive targets for therapeutic intervention. PAKs are activated by growth factor–mediated signaling and are negatively regulated by the tumor suppressor neurofibromatosis type 2 (NF2)/Merlin. Thus, tumors characterized by NF2 inactivation would be expected to show hyperactivated PAK signaling. On the basis of this rationale, we evaluated the status of PAK signaling in malignant mesothelioma, an aggressive neoplasm that is resistant to current therapies and shows frequent inactivation of NF2. We show that group I PAKs are activated in most mesotheliomas and mesothelioma cell lines and that genetic or pharmacologic inhibition of PAKs is sufficient to inhibit mesothelioma cell proliferation and survival. We also identify downstream effectors and signaling pathways that may contribute mechanistically to PAK-related tumorigenesis. Specifically, we show that inhibition of PAK results in attenuation of AKT and Raf–MAPK signaling and decreased tumor cell viability. Collectively, these data suggest that pharmacologic inhibition of group I PAKs may have therapeutic efficacy in tumors characterized by PAK activation. Mol Cancer Res; 10(9); 1178–88. ©2012 AACR.
Decreased Reelin Expression in the Left Prefrontal Cortex (BA9) in Chronic Schizophrenia Patients
Authors: Habl Gregor , Schmitt Andrea , Zink Mathias , von Wilmsdorff Martina , Yeganeh-Doost Peyman , Jatzko Alexander , Schneider-Axmann Thomas , Bauer Manfred , Falkai Peter
Published: July 2012

Background: Reelin is under epigenetic control and has been reported to be decreased in cortical regions in schizophrenia. Methods: To establish if expression of reelin is altered in specific cortical, hippocampal or thalamic regions of schizophrenia patients, we measured gene expression of reelin in a postmortem study of elderly patients with schizophrenia and non-affected controls in both hemispheres differentiating between gray and white matter. We compared cerebral postmortem samples (dorsolateral prefrontal cortex BA9 and BA46, superior temporal cortex BA22, entorhinal cortex BA28, sensoric cortex BA1–3, hippocampus, CA4, mediodorsal nucleus of the thalamus) from 12 schizophrenia patients with 13 normal subjects investigating gene expression of reelin in the gray and white matter of both hemispheres by in situ-hybridization. Results: The left prefrontal area (BA9) of schizophrenia patients revealed a decreased expression of reelin-mRNA of 29.1% in the white (p = 0.022) and 13.6% in the gray matter (p = 0.007) compared to the control group. None of the other regions examined showed any statistically significant differences. Conclusion: Since reelin is responsible for migration and synapse formation, the decreased gene expression of reelin in the left prefrontal area of schizophrenia patients points to neurodevelopmental deficits in neuronal migration and synaptic plasticity. However, our study group was small, and results should be verified using larger samples.
Semantic Network Disconnection in Formal Thought Disorder
Authors: Horn Helge , Jann Kay , Federspiel Andrea , Walther Sebastian , Wiest Roland , Müller Thomas , Strik Werner
Published: July 2012

Background: Structural and functional findings in schizophrenic patients with formal thought disorder (FTD) show abnormalities within left-side semantic areas. The present study investigate the network function of the involved brain regions as a function of FTD severity. Methods: We examined a group of 16 schizophrenia patients differing in FTD, but not in overall symptom severity, and 18 matched healthy controls. A passive word reading paradigm was applied during functional MRI (fMRI). A concatenated independent component analysis approach separated the fMRI signal into independent components, and spatial similarity was used to estimate the individual differences in spatial configuration of networks. Results: The semantic network was identified for both groups encompassing structures of the left inferior frontal gyrus, the left angular gyrus and the left middle temporal gyrus. The differences between the semantic networks of patients and controls increased with increasing severity of FTD. This difference was due to a decreasing contribution of the left inferior frontal gyrus (Brodmann area 45 and 47). Conclusion: Severity of FTD was correlated with a disruption of the left semantic network in schizophrenic patients. We suggest that FTD is a consequence of a frontal-parietal/temporal disconnection due to a complex interaction between structural and functional abnormalities within the left semantic network.
Eugen Bleuler’s Concept of Schizophrenia and Its Relevance to Present-Day Psychiatry
Authors: Hoff Paul
Published: July 2012

This paper links the historical perspective with the actual debate on the concept of schizophrenia. By this, two aims shall be accomplished. First, to prove that Eugen Bleuler’s (1857–1939) concept of ‘schizophrenia’ in its central parts was a clear step forward, as compared to previous approaches, especially the notion of ‘dementia praecox’, proposed and favored by French authors like Bénédict Augustin Morel (1809–1873) and, in Germany, by Emil Kraepelin (1856–1926). Bleuler considerably reduced the epistemological presuppositions of Kraepelin’s nosological model and coined the term ‘group of schizophrenias’, which was markedly broader and, as for prognosis, much less pessimistic. The second aim of this paper is to argue in favor of a continuous reflection upon psychiatry’s historical and epistemological basis which is regarded not just as ‘l’art pour l’art’, but as an indispensable component of psychiatry, clinically and scientifically.
Applicability of a Disposable Home Urinary Flow Measuring Device as a Diagnostic Tool in the Management of Males with Lower Urinary Tract Symptoms
Authors: Heesakkers John , Farag Fawzy , Pantuck Allan , Moore Katie , Radziszewski Piotr , Lucas Malcolm
Published: July 2012

Introduction: To investigate the accuracy of uroflowmetry with disposable QSingle compared to measurements with a home-based digital device and compared to a single clinical measurement. Patients and Methods: 60 men with lower urinary tract symptoms were included in a prospective, open-label, multicenter study. Uroflowmetry measurements were done using three devices/methods: single clinic-based method, followed by up to 12 measurements using the disposable home-based QSingle and up to 12 measurements using a home-based digital device. Subjective data on ease of use of QSingle and preference of patients was investigated and objective measures of Qmax and voided volume from the three devices were compared. Results: Mean Qmax values of 12, 13 and 16 ml/s were achieved with the QSingle device, standard clinic method, and digital device, respectively. Mean Qmax obtained with the QSingle device did not differ from that obtained with the clinic method. A significantly higher mean Qmax was recorded for the digital device. Mean voided volumes recorded with each device differed marginally. Handling capabilities of the QSingle device were considered good by all subjects. Conclusions: The accuracy of Qmax and voided volume mean measurements with QSingle was comparable to one standard clinic recording. QSingle offers a viable alternative to reduce the number of clinic visits and can be used by other caregivers.
The Effect of Pressure-Induced Mechanical Stretch on Vascular Wall Differential Gene Expression
Authors: Anwar M.A. , Shalhoub J. , Lim C.S. , Gohel M.S. , Davies A.H.
Published: July 2012

High blood pressure is responsible for the modulation of blood vessel morphology and function. Arterial hypertension is considered to play a significant role in atherosclerotic ischaemic heart disease, stroke and hypertensive nephropathy, whereas high venous pressure causes varicose vein formation and chronic venous insufficiency and contributes to vein bypass graft failure. Hypertension exerts differing injurious forces on the vessel wall, namely shear stress and circumferential stretch. Morphological and molecular changes in blood vessels ascribed to elevated pressure consist of endothelial damage, neointima formation, activation of inflammatory cascades, hypertrophy, migration and phenotypic changes in vascular smooth muscle cells, as well as extracellular matrix imbalances. Differential expression of genes encoding relevant factors including vascular endothelial growth factor, endothelin-1, interleukin-6, vascular cell adhesion molecule, intercellular adhesion molecule, matrix metalloproteinase-2 and -9 and plasminogen activator inhibitor-1 has been explored using ex vivo cellular or organ stretch models and in vivo experimental animal models. Identification of pertinent genes may unravel new therapeutic strategies to counter the effects of pressure-induced stretch on the vessel wall and hence minimise its notable complications.