bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of a Polymer-Based Microfluidic System for Electrophysiological Studies
Authors: Moss Eileen , Reddy Nakul , Chen Georgia , Shin Dong , Frazier A. Bruno
Published: November 2006

This paper presents the characterization of a polymer-based microfluidic system for whole-cell analysis manufactured using low-cost fabrication techniques. The multi-layer, laminate polyimide device contains features defined by a combination of laser ablation and microstenciling. This process requires minimal infrastructure and allows for a faster design-to- prototype cycle while providing the ability to integrate complex arrangements of multi-layer electrical functionality. The features include an array of analysis sites, a fluidic microchannel, and integrated electrodes for electrophysiological studies. Validation of the system for whole-cell analysis was first performed with impedance spectroscopy measurements collected on air, DI water, phosphate buffered saline (PBS), and clusters of human cancer cells. This was followed by testing the ability to use the device to control the movement and position of 10 µm diameter microbeads and dissociated cells.
Integrated Electrical Sensor Arrays in Microfluidic Networks
Authors: Cole Matthew C. , Kenis Paul J.
Published: November 2006

The design, fabrication, and characterization of a novel microfluidic sensing architecture are presented. The system allows for the position of a fluidic element to be monitored throughout a complex two-dimensional microfluidic network. Sensors consisting of small electrical components (resistors, capacitors, or conduction gaps) are placed within an interconnected fluidic network and are addressed using a multiplexing approach that allows an array of m×n sensors to be supported by only m+n+1 electrical contacts. The multiplexing relies on the fact that each sensing element is connected to two electrical leads, and each electrical lead is connected to multiple sensing elements. Herein, the basic principles of electrical resistive sensors are discussed and typical detection traces are presented. Finally, as a proof of the multiplexing concept, a 4×4 array of resistive sensors is used to monitor the passage of a discrete fluid plug through a microfluidic network.
Optimization of Low-Loss Al2O3 Waveguide Fabrication for Application in Active Integrated Optical Devices
Authors: Worhoff K. , Ay Feridun , Pollnau Markus
Published: November 2006

In this paper we will present the fabrication and properties of reactively co-sputtered Al2O3 layers, being a very promising host material for active integrated optics applications such as rare- earth ion doped laser devices. The process optimization towards a reactive co-sputtering process, which resulted in stable, target condition-independent deposition of Al2O3 layers with high optical quality will be discussed in detail. The loss value of as- deposited optical waveguides sputtered by the optimized process has been measured. The loss in the near infrared wavelength range was 0.3 dB/cm. Furthermore, Al2O3 material hosts fabricated by sputtering techniques are compatible with Si-based integrated optical technology and allow for uniform deposition over a large substrate area.
Azimuth Dependence of Light-Induced Ultrafast Insulator-to-Metal Phase Transition in VO2 Thin Film
Authors: Liu Huimin , Lysenko Sergie , Vikhnin Valentin , Rua Amond , Fernandez Felix
Published: November 2006

Using femtosecond laser excitation the light-induced ultrafast phase transition (PT) was observed in VO2 thin films deposited on different optically transparent substrates. The PT was characterized by transient absorption, reflection and nonlinear optical (NLO) response measurements. Degenerate-four-wave- mixing (DFWM) technique was also applied for time-resolved measurement of light-induced PT. While strong NLO response can always be observed in films on fused quartz substrates the response in films on C-cut sapphire substrates was diminished. However, it is much enhanced in films on R-cut sapphire. Further orientation dependent measurements show that the light- induced PT from insulator to metallic state is connected to the following lattice relaxation. In the interface layers a lattice distortion along c axis of the rutile structure or off-axis displacement may be engaged in the resultant PT. While the substrate lattice symmetry is in favour of this type of distortion the light-induced PT becomes enhanced.
Dielectric Relaxation in PbF2 - Doped and X-ray Irradiated CaF2 Crystals
Authors: Nicoara Irina , Munteanu Mihai , Pecingina-Garjoaba Nicolae , Stef Marius , Lighezan Liliana
Published: November 2006

Temperature and frequency dependence of the complex dielectric constant give information about the relaxation processes and permits the determination of the activation energy and the reciprocal frequency factor of the relaxation time. Pure and various concentration PbF2-doped CaF2 crystals have been grown using the vertical Bridgman method. The thin disks cut from the crystals have been X- ray irradiated. Room temperature optical absorption spectra were recorded for pure, doped and x-ray irradiated samples. Capacitance and dielectric loss measurements were performed on the samples over the temperature range 150-300 K at 1-100 kHz, and then the imaginary part of the dielectric constant has been calculated. The dielectric properties have been measured before and after X-irradiation, the activation energy and the reciprocal frequency factor have been calculated in order to characterize the observed relaxations.
Novel Low-Dielectric Constant Photodefinable Polyimides for Low-Temperature Polymer Processing
Authors: Henderson Clifford , Romeo Michael , Yamanaka Kazuhiro , Maeda Kazuhiko
Published: November 2006

A novel hexafluoroisopropanol (HFA)-substituted aromatic polyimide is reported that is prepared by chemical imidization of a poly(amic-acid) precursor obtained by polymerization of an HFA-substituted diamine and 6FDA. The HFA substituted polyimide shows good solubility in common organic casting solvents and 0.26 N TMAH alkaline developer. The HFA- containing side-group can be easily removed thermally at temperatures above 280 oC, which results in a dramatic decrease in the polyimide dielectric constant from 3.20 to 2.60 (at 1 MHz). A photosensitive composition based on 20 wt% THBP inhibitor loaded into the HFA-substituted polyimide is shown to produce good positive-tone imaging using I-line lithography. This strategy of incorporating thermally removable side-groups into polyimides to enhance solvent solubility and allow for solution processing while also permitting aqueous development enables production of low-k polymers that can be processed at significantly lower temperatures than conventional poly(amic acid) polymers and patterned using standard lithographic processing.
DNA-Wrapped Carbon Nanotubes Assembled on Gold Substrates
Authors: Sanchez-Pomales Germarie , Rivera-Vélez Nelson E. , Cabrera Carlos
Published: November 2006

In this report we combine the non-covalent functionalization of carbon nanotubes (CNTs) by DNA with the self-assembly technique to attach vertically aligned DNA-wrapped CNTs on gold substrates. The self-assembled adsorption of DNA-CNT complexes was characterized mainly by electrochemical techniques such as cyclic and linear sweep voltammetry. In addition, electrochemical desorption was used as a methodology to vary the surface coverage of the monolayer and to perform the complete removal of the species from the surface. The results suggest that the methodology used represents a straightforward route for the attachment of CNTs on solid substrates, and further studies will allow the development of novel nanodevices and sensors based on DNA-CNT self-assembled monolayers (SAMs).
Oxidation-Based, Redox-Dependent Hydrogen Bonding Utilizing Dimethylamino-Substituted Diarylureas
Authors: Smith Diane K. , Woods Jessica E.
Published: November 2006

Cyclic voltammetric studies of 1-phenyl-3-(4-N,N-dimethylamino)phenyl urea (UH) in CH2Cl2 in the presence of several pyridine derivatives are described. By itself, UH undergoes a reversible one electron oxidation to the radical cation, UH+, and a second less reversible oxidation at more positive potentials. Addition of ten equivalents of 1,8-naphthyridine or pyridine causes the second oxidation to shift 700 mV negative, resulting in a quasi-reversible two electron oxidation at the potential of the UH/UH+ wave. Possible explanations for the large shift are proton transfer between UH2+ and the guest or very strong hydrogen bonding between the two. Computer simulation studies and comparison to known pKa values suggest that neither by themselves are adequate to explain the observed voltammetry. A mechanism involving both hydrogen bonding and proton transfer is more likely.
Early and Long-Term Engraftment after Autologous Peripheral Stem Cell Transplantation in Acute Myeloid Leukemia Patients
Authors: Specchia Giorgina , Pastore Domenico , Mestice Anna , Liso Arcangelo , Carluccio Paola , Leo Manuela , Casanova Margherita , Sibilla Silvia , Giannoccaro Margherita , Liso Vincenzo
Published: November 2006

This study aimed to identify which subset of CD34+ cells might be the most predictive of early and long-term hematopoietic recovery following autologous peripheral blood stem cell (PBSC) transplantation (PBSCT) in adult acute myeloid leukemia (AML) patients. The relationships between the number of ‘mature’ subsets of CD34+ cells (CD34+/CD33+, CD34+/CD38+, CD34+/DR+ and CD34+/CD90–) and ‘immature’ subsets of CD34+ cells (CD34+/CD33–, CD34+/CD38–, CD34+/DR– and CD34+/CD90+) and early and long-term hemoglobin, neutrophil and platelet counts were studied in a homogeneous series (for disease, pre-transplant chemotherapy, mobilization chemotherapy, conditioning regimen) of 26 AML patients after autologous PBSCT. Cell counts were performed before and after cryopreservation, but only after thawing were the cell counts used for correlation with early and long-term engraftment. The number of CD34+/CD38– cells infused correlated with the neutrophil (r = 0.88, p < 0.005) and platelet counts (r = 0.67, p < 0.05) at 12 months after PBSCT. This correlation was better than that for the total CD34+ cell dose at 12 months (r = 0.36, p = 0.09 for neutrophil count and r = 0.48, p = 0.06 for platelets count). The number of CD34+/CD90+ cells was also correlated with the platelet counts at 6 (r = 0.70, p < 0.05) and 12 months (r = 0.80, p = 0.005) after PBSCT. This correlation was better than the total dose of CD34+ cells at 6 (r = 0.31, p = 0.3) and 12 months (r = 0.48, p = 0.06) for the platelet counts. CD34+ subset analysis suggests that for early engraftment the total number of CD34+ cells infused is more strongly correlated than the CD34+ subsets, whereas the CD34+/CD38– and CD34+/CD90+ subsets may be associated with sustained long-term neutrophil and platelet engraftment. These findings may help to predict the repopulating capacity of PBSCs in AML patients after autologous PBSCT, especially when a relatively low number of CD34+ cells is infused.
Does Hepcidin Affect Erythropoiesis in Hemodialysis Patients?
Authors: Eleftheriadis Theodoros , Kartsios Charalambos , Liakopoulos Vassilios , Antoniadi Georgia , Ditsa Maria , Papadopoulos Christos , Anifandis Georgios , Skirta Aliki , Markala Dimitra , Stefanidis Ioannis
Published: November 2006

Introduction: Prohepcidin is the precursor of hepcidin, a liver-derived peptide involved in iron metabolism by blocking its intestinal absorption and its release by the reticuloendothelial system. Iron overload and inflammation increase hepcidin expression, whereas anemia and hypoxia suppress it. In the present study prohepcidin levels were determined in the serum of hemodialysis (HD) patients and its correlations with iron metabolism markers, C-reactive protein (CRP) and hematocrit (Hct) were assessed. Patients and Methods: Forty-sixHD patients and 22 healthy volunteers were enrolled in the study. Hct, serum prohepcidin, CRP, iron, ferritin, transferrin saturation and transferrin receptors were measured. The weekly erythropoietin dose, last-month intravenous iron dose and the patients’ demographics were recorded. Results: In comparison to the healthy volunteers, the HD patients had higher serum ferritin, transferrin receptors and CRP, lower serum iron and similar transferrin saturation and prohepcidin levels. In the patient group prohepcidin levels were negatively correlated with Hct but not with any other of the examined parameters. Multiple linear regression analysis considering age, inflammation, iron adequacy, erythropoietin dose and prohepcidin levels revealed that prohepcidin was the predominant determinant of Hct. Conclusions: Taking into account the low Hct levels in the HD patients of our study, it seems plausible that the prohepcidin levels assessed in this group are inappropriately high. These functionally high prohepcidin levels may be associated with the factors that inhibit erythropoiesis in HD patients. On the other hand, the absence of other expected correlations indicates that further studies are needed in order to definitely clarify this aspect.
Variable Efficacy of Recombinant Human Erythropoietin in Anemic Pregnant Women with Different Forms of Heterozygous Hemoglobinopathy
Authors: Bencaiova Gabriela , Krafft Alexander , Burkhardt Tilo , Breymann Christian
Published: November 2006

Objective: The aim of this study was to determine the response to recombinant human erythropoietin (rhEPO) in anemic pregnant women with heterozygous hemoglobinopathies. Methods: A prospective study including 19 consecutive pregnant women with anemia and heterozygous hemoglobinopathy was performed. Treatment wasdivided into two phases: the initial low-dose phase and the subsequent high-rhEPO phase. In the initial phase, 3 × 10,000 U of rhEPO was administered with intravenous iron sucrose. In patients showing a poor response (Hb increase <1 g/dl) to low-dose rhEPO, the rhEPO dose was increased to 20,000 U per treatment in the subsequent phase. Results: All patients showed stimulation of erythropoiesis as evidenced by an increase in hemoglobin. In 13 patients, a good response to therapy was observed (mean Hb increase 1.6 ± 0.5 g/dl). In 6 patients, resistance to rhEPO was noted (mean Hb increase 0.5 ± 0.5 g/dl). The mean gestational age at the start of therapy was 28 weeks of gestation and at the end 32 weeks. The mean duration of a complete therapy was 3.5 weeks (range 2–4.5 weeks). If calculated for body weight, the initial low- rhEPO dose of 160.4 ± 30.6 U/kg body weight/treatment was increased to 320.9 ± 61.2 U/kg body weight/treatment in the subsequent phase. Conclusion: Response to rhEPO treatment differs widely in anemic pregnant patients with heterozygous hemoglobinopathy. Resistance was observed in anemic pregnant patients with the β-thalassemia trait originally from the Mediterranean region.
Simultaneous Hepatic Relapse of Non-Hodgkin’s Lymphoma and Hepatocellular Carcinoma in a Patient with Hepatitis C Virus-Related Cirrhosis
Authors: Ohtsubo Korenori , Oku Eijiro , Imamura Rie , Seki Ritsuko , Hashiguchi Michitoshi , Osaki Koichi , Yakushiji Kazuaki , Yoshimoto Kohji , Ogata Hideaki , Nagamatsu Hiroaki , Ando Eiji , Shimamatsu Kazuhide , Okamura Takashi , Sata Michio
Published: November 2006

We report a 66-year-old man with hepatitis C virus (HCV)-related cirrhosis and simultaneous hepatic relapse of non-Hodgkin’s lymphoma (NHL) and of hepatocellular carcinoma (HCC). Although the liver is frequently involved by NHL, hepatic colocalization of NHL and HCC is rarely detected by imaging techniques. HCV has been suggested to be lymphotrophic as well as hepatotrophic, and therefore has attracted speculation about a causative role in some cases of lymphoma. The patient had a past history of cutaneous diffuse large B cell lymphoma (DLBCL) in concurrence with HCC 32 months previously. Complete remission (CR) had been maintained for both diseases until February 2004, when ultrasonography and computed tomography (CT) showed multiple liver tumors. Two of these, appearing hyperattenuating in the arterial phase of contrast-enhanced CT, were diagnosed histopathologically as HCC, and treated with radiofrequency ablation. The other tumors, hypoattenuating in the portal phase CT, were diagnosed histopathologically as DLBCL, and treated with cyclophosphamide, tetrahydropyranyl-Adriamycin, vincristine and prednisolone (THP-COP) in combination with rituximab. CR was achieved for both DLBCL and HCC. Given the previously demonstrated immune system tropism and perturbation by HCV, the virus might have contributed to the occurrence of the NHL as well as the HCC.
Pseudo-Pelger-Huët in Kidney-Transplanted Patients
Authors: Dusse Luci Maria Sant’Ana , Morais e Silva Rívia Mara , Freitas Vânia Maria , Medeiros de Paula Geraldo Majella , Vieira Lauro Mello , Carvalho Maria das Graças
Published: November 2006

Pelger-Huët anomaly is an inherited condition characterized by hyposegmentation of the neutrophil nucleus and excessive chromatin clumping. Acquired Pelger-Huët, also known as pseudo-Pelger-Huët, has been described in several clinical conditions including transplant recipients who received immunosuppressive drugs. The incidence of pseudo-Pelger-Huët in kidney transplant patients, characterized as neutrophil dysplasia, was observed in 9 of 170 patients (5.3%) at the São Francisco Hospital de Assis, Belo Horizonte, Brazil. Awareness of possible circulating neutrophil alterations in transplant patients is important for laboratory professionals who should report these findings of cell changes. It should be highlighted that the poor segmentation and the chromatin hypercondensation observed initially in pseudo-Pelger-Huët patients can be suggestive of early-stage neutrophils. Only a combination of laboratory and clinical data will facilitate a better understanding of this anomaly and its correct follow-up and management.
L’appareil musculaire régit le développement squelettique
Authors: Schoenau Eckhard
Published: November 2006

La présente analyse traite de concepts méthodologiques dans l’évaluation de la fonction des muscles squelettiques et de l’adaptation osseuse. La propriété capitale de l’os est aujourd’hui considérée comme étant la résistance et non le poids, et le contrôle de cette résistance paraît être principalement dû à l’effet des charges mécaniques s’exerçant sur l’os. La contraction musculaire place la charge physiologique la plus élevée sur l’os et, de ce fait, la stabilité osseuse doit être adaptée à la force musculaire (unité fonctionnelle ostéomusculaire). Les suggestions et recommandations décrites soulignent un nouveau concept: la masse et la résistance osseuses ne doivent pas être reliées à l’âge mais, comme le montrent des données de plus en plus nombreuses, elles pourraient désormais être liées à la fonction musculaire. Selon cette analyse, il n’existe aucune entité correspondant à une «masse osseuse maximale». De nombreuses études sont en cours afin d’évaluer si ces nouvelles approches accroissent la sensibilité et la spécificité du pronostic de fracture chez un sujet. De plus, le domaine de recherche de nombreux investigateurs en matière de physiologie osseuse se déplace de la masse osseuse vers la géométrie ou la résistance des os et vers leur relation à l’appareil musculaire qui les régit.
Nutrition et sport au cours de l’enfance et de l’adolescence: satisfaire les demandes métaboliques liées à la croissance et à l’exercice physique
Authors: Zanker C.L.
Published: November 2006

Au cours de l’enfance et de l’adolescence, les principaux objectifs sont une croissance et une maturation optimales. Ces processus développementaux demandent un bilan énergétique et azoté positif. Une activité physique régulière peut améliorer le développement de l’enfant et de l’adolescent mais un entraînement physique très intensif peut réduire les stocks d’énergie et d’azote de l’organisme, qui doivent être tous deux reconstitués par l’alimentation. Les adolescents physiquement actifs sont sensibles aux troubles de l’alimentation, ce qui peut aboutir à une malnutrition protéino-énergétique. Les conséquences d’un bilan énergétique et azoté négatif incluent un délai, un retard ou un arrêt de la croissance et de la maturation pubertaire. Actuellement, quelques rares données suggèrent qu’un entraînement physique a un impact négatif direct sur la croissance et la maturation. Une alimentation bien équilibrée est essentielle pour l’entretien des performances physiques et la préservation de la santé chez tous les sujets physiquement actifs, quel que soit leur âge. Les aliments apportent les éléments chimiques nécessaires à la production d’énergie par exercice des muscles squelettiques, au réapprovisionnement des stocks d’énergie après l’exercice et à la régénérescence des muscles endommagés. Les besoins alimentaires des enfants physiquement actifs se modifient avec la croissance et la progression de la puberté. Le dégre de maturité est un important déterminant des réponses métaboliques et physiologiques à l’exercice et influence ainsi tant les capacités de performances physiques que les besoins alimentaires. Des études du métabolisme énergétique chez les enfants suggèrent que ces derniers sont bien équipés pour une activité aérobie soutenue, mais que leur capacité de performance anaérobie est limitée par leur degré de maturité. Il est important de noter que des limitations éthiques s’opposent au type de recherches détaillées et invasives qui ont identifié les besoins nutritionnels des adultes physiquement actifs. Néanmoins, il semblerait que, comme ces adultes, les enfants physiquement actifs ont des besoins alimentaires plus élevés pour l’énergie, les glucides, les protéines et l’eau que leurs homologues sédentaires. Le présent article justifie les besoins nutritionnels des enfants sportifs sur la base des besoins physiologiques et métaboliques nécessaires à la survie, à la croissance et à l’activité physique.
Puberté et sports de compétition chez l’adolescente
Authors: Klentrou Panagiota (Nota)
Published: November 2006

Ces dernières décennies, la participation croissante de jeunes enfants à un entraînement physique intensif a été à l’origine de préoccupations quant aux effets potentiels de cette situation sur la croissance et la maturation. La puberté se caractérise chez l’être humain par d’importantes modifications hormonales responsables de la maturation physique et sexuelle. Un entraînement intensif avant la puberté, ainsi que les effets métaboliques potentiels du régime alimentaire adopté, peuvent altérer la fonction hypothalamo-hypophysaire, et le moment auquel l’entraînement athlétique débute a été impliqué à titre de facteur de retard de la ménarche et de la maturation sexuelle chez les sportives. D’autre part, certaines études ont suggéré qu’un retard de la ménarche est probablement dû à des facteurs génétiques. Les jeunes filles qui sont matures plus tardivement sélectionnent souvent elles-mêmes des sports qui favorisent une petite taille ou une grande minceur, ou sont recrutées par les entraîneurs pour ceux-ci. La composition corporelle a été également utilisée afin d’expliquer simultanément le retard de la ménarche et les irrégularités menstruelles observées chez les sportives de haut niveau. Une prévalence plus élevée des dysfonctions menstruelles a été décrite chez des adolescentes pratiquant des sports dépendant du poids, comparativement à celle observée avec d’autres activités sportives. Toutefois, comme récemment suggéré, il n’existe aucune relation directe de cause à effet entre la corpulence et la reproduction et, de fait, c’est la disponibilité de l’énergie, et non les tissus adipeux, qui régule la fonction reproductive chez la femme. Des recherches supplémentaires sont justifiées afin de mieux explorer cette interaction entre les modifications à court terme de la disponibilité de l’énergie et l’aménorrhée due au sport chez l’adolescente. Nous concluons que, en raison des nombreux facteurs influençant de façon avérée la ménarche et la menstruation, le rôle du seul entraînement physique à titre de facteur causal d’un retard pubertaire et d’irrégularités menstruelles chez les jeunes femmes sportives est encore mal défini. Des recherches comportant des études longitudinales sont nécessaires afin de déterminer si les différences de maturité observées entre des jeunes femmes sportives ou non résultent de la nature ou de la nutrition, et quel est l’équilibre entre ces deux facteurs.
Cytogenetic genotype-phenotype studies: Improving genotyping, phenotyping and data storage
Authors: Feenstra I. , Brunner H.G. , van Ravenswaaij C.M.A.
Published: November 2006

High-resolution molecular cytogenetic techniques such as genomic array CGH and MLPA detect submicroscopic chromosome aberrations in patients with unexplained mental retardation. These techniques rapidly change the practice of cytogenetic testing. Additionally, these techniques may improve genotype-phenotype studies of patients with microscopically visible chromosome aberrations, such as Wolf-Hirschhorn syndrome, 18q deletion syndrome and 1p36 deletion syndrome. In order to make the most of high-resolution karyotyping, a similar accuracy of phenotyping is needed to allow researchers and clinicians to make optimal use of the recent advances. International agreements on phenotype nomenclature and the use of computerized 3D face surface models are examples of such improvements in the practice of phenotyping patients with chromosomal anomalies. The combination of high-resolution cytogenetic techniques, a comprehensive, systematic system for phenotyping and optimal data storage will facilitate advances in genotype-phenotype studies and a further deconstruction of chromosomal syndromes. As a result, critical regions or single genes can be determined to be responsible for specific features and malformations.
Array-based comparative genomic hybridization and copy number variation in cancer research
Authors: Cho E.K. , Tchinda J. , Freeman J.L. , Chung Y.-J. , Cai W.W. , Lee C.
Published: November 2006

Array-based comparative genomic hybridization (aCGH) is a molecular cytogenetic technique used in detecting and mapping DNA copy number alterations. aCGH is able to interrogate the entire genome at a previously unattainable, high resolution and has directly led to the recent appreciation of a novel class of genomic variation: copy number variation (CNV) in mammalian genomes. All forms of DNA variation/polymorphism are important for studying the basis of phenotypic diversity among individuals. CNV research is still at its infancy, requiring careful collation and annotation of accumulating CNV data that will undoubtedly be useful for accurate interpretation of genomic imbalances identified during cancer research.
Molecular parameters associated with insulinoma progression: chromosomal instability versus p53 and CK19 status
Authors: Jonkers Y.M.H. , Claessen S.M.H. , Veltman J.A. , Geurts van Kessel A. , Dinjens W.N.M. , Skogseid B. , Ramaekers F.C.S. , Speel E.-J.M.
Published: November 2006

Insulinomas represent the predominant syndromic subtype of endocrine pancreatic tumors (EPTs). Their metastatic potential cannot be predicted reliably using histopathological criteria. In the past few years, several attempts have been made to identify prognostic markers, among them TP53 mutations and immunostaining of p53 and recently cytokeratin 19 (CK19). In a previous study using conventional comparative genomic hybridization (CGH) we have shown that chromosomal instability (CIN) is associated with metastatic disease in insulinomas. It was our aim to evaluate these potential parameters in a single study. For the determination of CIN, we applied CGH to microarrays because it allows a high-resolution detection of DNA copy number changes in comparison with conventional CGH as well as the analysis of chromosomal regions close to the centromeres and telomeres, and at 1pter→p32, 16p, 19 and 22. These regions are usually excluded from conventional CGH analysis, because they may show DNA gains in negative control hybridizations. Array CGH analysis of 30 insulinomas (15 tumors of benign, eight tumors of uncertain and seven tumors of malignant behavior) revealed that ≧20 chromosomal alterations and ≧6 telomeric losses were the best predictors of malignant progression. A subset of 22 insulinomas was further investigated for TP53 exon 5–8 gene mutations, and p53 and CK19 expression. Only one malignant tumor was shown to harbor an arginine 273 serine mutation and immunopositivity for p53. CK19 immunopositivity was detected in three malignant tumors and one tumor with uncertain behavior. In conclusion, our results indicate that CIN as well as telomeric loss are very powerful indicators for malignant progression in sporadic insulinomas. Our data do not support a critical role for p53 and CK19 as molecular parameters for this purpose.
Bcl-2 Phosphorylation Has Pathological Significance in Human Breast Cancer
Authors: Matsuyoshi Syuichi , Shimada Keiji , Nakamura Mitsutoshi , Ishida Eiwa , Konishi Noboru
Published: November 2006

The anti-apoptotic molecule, Bcl-2, is well known to play an important role in the chemoresistance of breast cancer. We have previously demonstrated that phosphorylation of Fas-associated death domain-containing protein (FADD) at 194 serine through c-jun NH2-terminal kinase (JNK) activation sensitizes breast cancer cells to chemotherapy through accelerating cell cycle arrest at G2/M, and that Bcl-2 phosphorylation downstream of JNK/FADD plays an important role in cell growth suppression by paclitaxel. In this study, the clinicopathological association of phosphorylated Bcl-2 (P-Bcl-2) with estrogen, progesterone, c-erbB-2 receptors, p53 expressions and phosphorylated FADD/JNK (P-FADD/JNK) was analyzed immunohistochemically using 107 human breast cancer specimens. Expression of P-Bcl-2 was found to significantly correlate with lymphatic invasion, lymph node metastasis, but not histological differentiation, tumor grade or vascular and fatty invasion. The positivity of P-Bcl-2 was also significantly correlated to that of P-FADD/JNK. Thus, P-Bcl-2 as well as the P-FADD/JNK parameter might be useful markers for cancer progression, independent of the hormone receptor status, in human breast cancers.
Baló’s Encephalitis Periaxialis Concentrica
Authors: Pearce J.M.S.
Published: November 2006

In 1928, Baló described a law student with an unusual fatal illness marked by aphasia and a right hemiplegia, with later optic neuritis and normal cerebrospinal fluid. At autopsy, he found a disease of the white matter characterised by foci varying in size from a lentil to that of a pigeon’s egg and presenting gray softening and, in part, concentricity, where the medullary sheaths were destroyed and the axis cylinders were intact. He was uncertain whether this was a variant of acute multiple sclerosis or of Schilder’s disease. The basis of concentric sclerosis is still unclear though current opinion favours a variant of acute multiple sclerosis.
The Potential Salmonella aroA– Vaccine Strain Is Safe and Effective in Young BALB/c Mice
Authors: Burns-Guydish Stacy M. , Zhao Hui , Stevenson David K. , Contag Christopher H.
Published: November 2006

Background: Due to the increased susceptibility of neonates to pathogens including those with mutations, the use of live vaccine strategies in the human population may present a potential risk to the young. Objectives: The specific aim of this study was to assess the risk that prospective Salmonella enterica serovar Typhimurium vaccine strains pose for the neonate and determine whether the strains are an effective vaccine by assessing the adaptive immune response. Methods: To evaluate the susceptibility of young mice to potential vaccine strains, S. typhimuriumaroA– and ΔphoP mutant strains were labeled by chromosomal insertion of the lux operon – this serves as a readily traceable marker of infection using noninvasive imaging methods. BALB/c mice ages 1, 2, 4, and 6 weeks of age were fed the bioluminescent aroA– or ΔphoP strains and the course of infection was monitored by in vivobioluminescence imaging. In addition, blood samples were collected post-inoculation to assess the IgG response of mice to S. typhimurium LPS. Results: Young BALB/c mice were not susceptible to the aroA– strain in contrast to their susceptibility to the ΔphoP strain at a dose of 109 colony forming units. Delivery by oral feeding of the aroA– and ΔphoP strains in young mice also produced a robust IgG anti-LPS response. Conclusion: Here, we report that young 2-week-old mice orally fed the bioluminescent aroA–S. typhimurium strain were not susceptible to infection and elicited a protective immune response.
Tubular Disorders in Low Birth Weight Neonates after Prolonged Antibiotic Treatment
Authors: Giapros Vasileios I. , Papadimitriou Foteini K. , Andronikou Styliani K.
Published: November 2006

Background: Aminoglycosides (AGs) and vancomycin (VM) are potentially nephrotoxic antibiotics and their co-administration increases the incidence of nephrotoxicity in adult patients. Their combined effects on renal function in extremely low birth weight (ELBW) infants (<1,000 g) have not been previously reported. Objectives: Investigation of tubular disturbances in five ELBW neonates following repeated and prolonged treatment with a variety of AGs combined with VM. Results: The drug levels were maintained in the neonatal therapeutic range. Renal tubular wasting of potassium, phosphate, and calcium, along with hypokalemia, was documented in all neonates studied while associated hypophosphatemia was observed in three of the five neonates and a transient rise in serum creatinine in four. The renal disturbances resolved completely 1–2 weeks after cessation of treatment. Conclusion: Renal tubular disturbances due to AG and VM treatment in ELBW neonates may be more common than they are diagnosed. Early detection and appropriate electrolyte supplementation may help to normalize serum electrolyte levels in these infants.
Cosegregation of a Novel Homozygous CYP11B1 Mutation with the Phenotype of Non-Classical Congenital Adrenal Hyperplasia in a Consanguineous Family
Authors: Peters C.J. , Nugent T. , Perry L.A. , Davies K. , Morel Y. , Drake W.M. , Savage M.O. , Johnston L.B.
Published: November 2006

We report a novel missense mutation of CYP11B1 causing non-classical 11β-hydroxylase deficiency in 3 members of a consanguineous Turkish family. Two siblings presented with clinical evidence of precocious pseudopubarche. Biochemistry suggested 11β-hydroxylase deficiency and genetic analysis revealed that they were homozygous for the missense mutation L489S within exon 9 of the CYP11B1 gene. The unaffected parents were heterozygotes for the same mutation. In addition, a paternal aunt of the affected siblings presenting with primary infertility and mild hirsutism was found to have the same homozygous mutation. This is the first report of a homozygous mutation in non-classical congenital adrenal hyperplasia that cosegregates with clinical phenotype. The significance of the missense mutation L489S in CYP11B1 is further supported by the conservation of leucine at position 489 in CYP11 genes in eleven other species. Molecular modelling of the enzyme suggests that the mutation L489S in CYP11B1 may alter the enzyme’s substrate-binding affinity. These findings suggest that this homozygous mutation affects 11β-hydroxylase function, resulting in the clinical features of non-classical adrenal hyperplasia in this family.
An Experimental Study of Tympanic Membrane and Manubrium Vibrations in Rats
Authors: Akache F. , Funnell W.R.J. , Daniel S.J.
Published: November 2006

Rats are potentially very useful for auditory research because the middle ear structures are easily approachable and because rats are relatively inexpensive. The goal of the present study was to better characterize the mechanics of the rat middle ear by measuring frequency responses at multiple points on the tympanic membrane and manubrium. A laser Doppler vibrometer was used to measure the vibrations. Measurements were made on 7 rats. Tympanic membrane vibrations are presented for 7 different points in the frequency range of 1–10 kHz. The repeatability of the measurements and the interanimal variability at the umbo are also presented. The vibration modes of the tympanic membrane and manubrium were investigated.
Melatonin and Immunomodulation: Connections and Potential Clinical Applications
Authors: Giannoulia-Karantana Aglaia , Vlachou Antonia , Polychronopoulou Sophia , Papassotiriou Ioannis , Chrousos George P.
Published: November 2006

Melatonin is the main hormone secreted by the pineal gland in the human brain. It has a strong impact on the sleep-wake cycle and is considered a general modulator of the human circadian rhythm. Apart from these well-established properties, melatonin possesses immunomodulatory, antioxidative and antiinflammatory properties. The potential ability of this hormone to act synergistically with several cytokines by enhancing their antitumoral activity and dramatically decreasing their adverse effects has placed melatonin among the new and promising agents in cancer immunotherapy. The use of the neurohormone alone or in combination with cytokines and traditional chemotherapeutic drugs is currently under vigorous investigation. Experimental and clinical trials have already depicted some of the immunomodulatory and antitumor effects of melatonin, delineating the need for further research in this field.
Modulation of T Cell Responses in HTLV-1 Carriers and in Patients with Myelopathy Associated with HTLV-1
Authors: Santos Silvane B. , Porto Aurélia F. , Muniz André Luiz , Luna Tania , Nascimento Márcia C. , Guerreiro Jaqueline B. , Oliveira-Filho Jamary , Morgan Daniel J. , Carvalho Edgar M.
Published: November 2006

Objective: Human T lymphotropic virus-type 1 (HTLV-1) activates the immune system leading to a persistent and exacerbated T-cell response with increased production of IFN-γ and TNF-α. Overproduction of pro-inflammatory cytokines is correlated with the development of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), although some HTLV-1 carriers also show high levels of these cytokines. In this study, the ability of regulatory cytokines and cytokine antagonists to inhibit spontaneous IFN-γ production was investigated. Method: IFN-γ levels were measured by ELISA before and after addition of cytokines or anti-cytokines. Results: Addition of IL-10 significantly reduced spontaneous IFN-γ synthesis in cell cultures from HTLV-1 carriers, while no differences were observed in HAM/TSP patients. There was also a tendency to decreased IFN-γ levels in cell cultures from HTLV-1 carriers with exogenous addition of TGF-β. In paired analysis, neutralization of IL-2 significantly decreased IFN-γ production in HTLV-1 carriers but not in HAM/TSP patients. Neutralization of IL-15 was less effective than neutralization of IL-2 in modulating IFN-γ production. In HTLV-1 carriers, anti-IL-2 and simultaneous addition of anti-IL-2 and anti-IL-15 decreased IFN-γ synthesis by 46 and 64%, respectively, whereas in patients with HAM/TSP simultaneous neutralization of both anti-cytokines only decrease IFN-γ levels by 27%. Conclusions: Although a large proportion of HTLV-1 carriers produced high levels of pro-inflammatory cytokines similar to those observed in HAM/TSP patients, immune response can be downregulated by cytokines or cytokine antagonists in most HTLV-1 carriers. This modulation can be an important step in the prevention of tissue damage and progression from the HTLV-1 carrier state to HAM/TSP.
High-Dose Allopurinol Improves Endothelial Function by Profoundly Reducing Vascular Oxidative Stress and Not by Lowering Uric Acid
Authors: George Jacob , Carr Elaine , Davies Justine , Belch J.J.F. , Struthers Allan
Published: November 2006

Background—

Allopurinol has been shown to improve endothelial function in chronic heart failure. This study aimed to establish its mechanism of action and to construct a dose–response curve for the effect of allopurinol.

Methods and Results—

Two randomized, placebo-controlled, double-blind, crossover studies were performed for 1 month on patients with New York Heart Association Class II–III chronic heart failure, comparing 300 mg allopurinol, 600 mg allopurinol, and placebo for the first study and 1000 mg probenecid versus placebo in the second study. Endothelial function was assessed by standard forearm venous occlusion plethysmography. Allopurinol 600 mg/d significantly increased forearm blood flow response to acetylcholine compared with both allopurinol 300 mg/d and placebo (% change in forearm blood flow [mean±SEM]: 240.31±38.19% versus 152.10±18.21% versus 73.96±10.29%,
P
<0.001). For similar levels of urate lowering, the uricosuric agent probenecid had no effect on endothelial function. Sodium nitroprusside response was unchanged by all treatments. Vitamin C and acetylcholine coinfusion data showed that 600 mg/d allopurinol completely abolished the oxidative stress that was sensitive to high-dose vitamin C.

Conclusions—

For the first time, we have shown that a steep dose–response relationship exists between allopurinol and its effect on endothelial function. We also showed that the mechanism of improvement in endothelial function with allopurinol lies in its ability to reduce vascular oxidative stress and not in urate reduction. The reduction in vascular oxidative stress was profound because high-dose allopurinol totally abolished the oxidative stress that was sensitive to the high-dose vitamin C that was used in this study.
Theoretical Impact of the Injection of Material Into the Myocardium
Authors: Wall Samuel T. , Walker Joseph C. , Healy Kevin E. , Ratcliffe Mark B. , Guccione Julius M.
Published: November 2006

Background—

To treat cardiac injuries created by myocardial infarcts, current approaches seek to add cells and/or synthetic extracellular matrices to the damaged ventricle to restore function. Because definitive myocardial regeneration remains undemonstrated, we propose that cardiac changes observed from implanted materials may result from altered mechanisms of the ventricle.

Methods and Results—

We exploited a validated finite element model of an ovine left ventricle with an anteroapical infarct to examine the short-term effect of injecting material to the left ventricular wall. The model’s mesh and regional material properties were modified to simulate expected changes. Three sets of simulations were run: (1) single injection to the anterior border zone; (2) therapeutic multiple border zone injections; and (3) injection of material to the infarct region. Results indicate that additions to the border zone decrease end-systolic fiber stress proportionally to the fractional volume added, with stiffer materials improving this attenuation. As a potential therapy, small changes in wall volume (≈4.5%) reduce elevated border zone fiber stresses from mean end-systole levels of 28.2 kPa (control) to 23.3 kPa (treatment), similar to levels of 22.5 kPA computed in remote regions. In the infarct, injection improves ejection fraction and the stroke volume/end-diastolic volume relationship but has no effect on the stroke volume/end-diastolic pressure relationship.

Conclusions—

Simulations indicate that the addition of noncontractile material to a damaged left ventricular wall has important effects on cardiac mechanics, with potentially beneficial reduction of elevated myofiber stresses, as well as confounding changes to clinical left ventricular metrics.
Paradoxical Body
Authors: Gil José
Published: November 2006

The articles in this first installment of a series on choreography that considers the relationship between philosophy and dance interrogate conceptions of the body, movement, and language. Translated for the first time into English, the selection by José Gil reads the dancing body as paradoxical through the writings of Gilles Deleuze and Félix Guattari; and the chapter by Peter Sloterdijk examines modernity's impulse toward movement and posits a critical theory of mobilization. An interview with choreographer Hooman Sharifi accompanies a meditation on his recent performance.
Mobilization of the Planet from the Spirit of Self-Intensification
Authors: Sloterdijk Peter
Published: November 2006

The articles in this first installment of a series on choreography that considers the relationship between philosophy and dance interrogate conceptions of the body, movement, and language. Translated for the first time into English, the selection by José Gil reads the dancing body as paradoxical through the writings of Gilles Deleuze and Félix Guattari; and the chapter by Peter Sloterdijk examines modernity's impulse toward movement and posits a critical theory of mobilization. An interview with choreographer Hooman Sharifi accompanies a meditation on his recent performance.
What's the Matter?: Shakti's (Re)Collection of Race, Nationhood, and Gender
Authors: Kumar Anita
Published: November 2006

The 2005 Student Essay Contest winner weaves together the narratives of members of Viji Prakash's Shakti bharatanatyam school community, dancing in and out of positions of marginality to unravel the notion of group identity as cohesive, homogenous, and pure as she confronts her own performance and corporealization of South Asian American identity.
What the Fox Might Have Said About Inhabiting Shenzhen: The Ambiguous Possibilities of Social- and Self-Transformation in Late Socialist Worlds
Authors: O'Donnell Mary Ann
Published: November 2006

Established in 1980 as a “Special Economic Zone,” Shenzhen Municipality is an emblem of China's modernity, where the planned economy of the socialist state transitioned into a market-based system. The new environment shaped new social relations, enabling individuals to reimagine themselves. The subjective and social metamorphoses are examined through an analysis of the process of composing the performance piece Hushuo.
Deficits in Movement Planning and Intrinsic Coordinate Control in Ideomotor Apraxia
Authors: Jax Steven A. , Buxbaum Laurel J. , Moll Adrienne D.
Published: November 2006

Two central issues in the field of motor control are the coordinate frame in which movements are controlled and the distinction between movement planning and online correction. In this study we used these issues to frame several hypotheses about the deficits underlying ideomotor apraxia (IMA). In particular, we examined whether ideomotor apraxics exhibited (1) deficits in movement control in intrinsic (body relative) coordinates with better control in extrinsic (workspace relative) coordinates, (2) deficits in movement planning that are compensated for by an overreliance on online correction, or (3) both deficits. Patients with IMA and two comparison groups performed movement tasks that relied preferentially on either intrinsic or extrinsic coordinate control when online correction was either possible or impossible. Participants performed posture imitation and grasp imitation movements to body- and object-relative end positions in the presence or absence of visual feedback. Consistent with the intrinsic coordinate control hypothesis, patients with IMA showed a significantly greater disparity than the other two groups between movements made to body-relative and object-relative targets as well as between imitation of meaningless postures and grasping. Consistent with the correction overreliance hypothesis, the IMA group was more disrupted than the other groups by the removal of vision. Thus, IMA patients exhibit behavioral patterns consistent with both deficient intrinsic coordinate control and overreliance upon visual feedback. Finally, lesion analysis suggests that damage to the left inferior parietal lobe (Brodmann's areas 39 and 40) may play a key role in both behavioral deficits.