bluuebunny/crossref_metadata_2025 huggingface dataset:
Double‐stranded RNA‐dependent protein kinase (PKR) is downregulated by phorbol ester
Authors: Zhou Yan , Chase Barbara I. , Whitmore Mark , Williams Bryan R. G. , Zhou Aimin
Published: March 2005

The double‐stranded RNA‐dependent protein kinase (PKR) is one of the key mediators of interferon (IFN) action against certain viruses. PKR also plays an important role in signal transduction and immunomodulation. Understanding the regulation of PKR activity is important for the use of PKR as a tool to discover and develop novel therapeutics for viral infections, cancer and immune dysfunction. We found that phorbol 12‐myristate 13‐acetate (PMA), a potent activator of protein kinase C (PKC), decreased the level of autophosphorylated PKR in a dose‐ and time‐dependent manner in IFN‐treated mouse fibroblast cells. Polyinosinic–polycytidylic acid (poly I:C) treatment enhanced the activity of PKR induced by IFN, but did not overcome the PMA‐induced reduction of PKR autophosphorylation. Western blot analysis with a monoclonal antibody to mouse PKR revealed that the decrease of PKR autophosphorylation in cells by PMA was a result of PKR protein degradation. Selective PKC inhibitors blocked the degradation of PKR stimulated by PMA, indicating that PKC activity was required for the effect. Furthermore, we also found that proteasome inhibitors prevented PMA‐induced down regulation of PKR, indicating that an active proteasome is required. Our results identify a novel mechanism for the post‐translational regulation of PKR.
Novel target genes of the Wnt pathway and statistical insights into Wnt target promoter regulation
Authors: Ziegler Slava , Röhrs Sonja , Tickenbrock Lara , Möröy Tarik , Klein‐Hitpass Ludger , Vetter Ingrid R. , Müller Oliver
Published: March 2005

The Wnt pathway controls biological processes via the regulation of target gene expression. The expression of direct Wnt target genes, e.g. cyclin D1and MYC, is activated by the transcription factor TCF, which binds to specific sequence motifs in the promoter. Indirect target genes are regulated via transcription regulators, which are targets of the Wnt pathway. As an example, MYC regulates the MYC interacting zinc finger protein‐1 (MIZ‐1), which is able to inhibit the expression of the indirect target p21WAF1. We intended to identify new Wnt target genes and to get a deeper insight into the regulatory mechanisms of Wnt target gene expression. For this we analyzed the differential expression pattern of Wnt‐1 activated cells by microarray analysis. We identified 43 sequences including eight expressed sequence tags (ESTs), which showed increased transcript levels, and 104 sequences including 19 ESTs with decreased RNA levels. Northern blot and real‐time quantitative PCR analysis of the differential expression levels of 15 genes confirmed the differential expression trends of eight candidate genes. When the Wnt pathway was regulated at the lower level of glycogen synthase kinase‐3β (GSK‐3β) or adenomatous polyposis coli (APC), we detected discrepant expression trends. We compared the number of binding sites of transcription factors in the genomic regions of all candidate target genes with the number of sites in control genes. We found that the genomic regions of the down‐regulated genes include an increased number of putative MIZ‐1 binding sites. Our study introduces several new Wnt target genes and provides indications that the specific gene expression pattern depends on the type of the activation trigger or the level of interference with the Wnt pathway. Furthermore, our data indicate that a high proportion of Wnt target genes are regulated by indirect mechanisms.
Exploring the GluR2 ligand‐binding core in complex with the bicyclical AMPA analogue (S)‐4‐AHCP
Authors: Nielsen Bettina B. , Pickering Darryl S. , Greenwood Jeremy R. , Brehm Lotte , Gajhede Michael , Schousboe Arne , Kastrup Jette S
Published: March 2005

The X‐ray structure of the ionotropic GluR2 ligand‐binding core (GluR2‐S1S2J) in complex with the bicyclical AMPA analogue (S)‐2‐amino‐3‐(3‐hydroxy‐7,8‐dihydro‐6H‐cyclohepta[d]‐4‐isoxazolyl)propionic acid [(S)‐4‐AHCP] has been determined, as well as the binding pharmacology of this construct and of the full‐length GluR2 receptor. (S)‐4‐AHCP binds with a glutamate‐like binding mode and the ligand adopts two different conformations. The Ki of (S)‐4‐AHCP at GluR2‐S1S2J was determined to be 185 ± 29 nm and at full‐length GluR2(R)o it was 175 ± 8 nm. (S)‐4‐AHCP appears to elicit partial agonism at GluR2 by inducing an intermediate degree of domain closure (17°). Also, functionally (S)‐4‐AHCP has an efficacy of 0.38 at GluR2(Q)i, relative to (S)‐glutamate. The proximity of bound (S)‐4‐AHCP to domain D2 prevents full D1–D2 domain closure, which is limited by steric repulsion, especially between Leu704 and the ligand.
The Ets transcription factor ESE‐1 mediates induction of the COX‐2 gene by LPS in monocytes
Authors: Grall Franck T. , Prall Wolf C. , Wei Wanjiang , Gu Xuesong , Cho Je‐Yoel , Choy Bob K. , Zerbini Luiz F. , Inan Mehmet S. , Goldring Steven R. , Gravallese Ellen M. , Goldring Mary B. , Oettgen Peter , Libermann Towia A.
Published: March 2005

Cyclooxygenase‐2 (COX‐2) is a key enzyme in the production of prostaglandins that are major inflammatory agents. COX‐2 production is triggered by exposure to various cytokines and to bacterial endotoxins. We present here a novel role for the Ets transcription factor ESE‐1 in regulating the COX‐2 gene in response to endotoxin and other pro‐inflammatory stimuli. We report that the induction of COX‐2 expression by lipopolysaccharide (LPS) and pro‐inflammatory cytokines correlates with ESE‐1 induction in monocyte/macrophages. ESE‐1, in turn, binds to several E26 transformation specific (Ets) sites on the COX‐2 promoter. In vitro analysis demonstrates that ESE‐1 binds to and activates the COX‐2 promoter to levels comparable to LPS‐mediated induction. Moreover, we provide results showing that the induction of COX‐2 by LPS may require ESE‐1, as the mutation of the Ets sites in the COX‐2 promoter or overexpression of a dominant‐negative form of ESE‐1 inhibits LPS‐mediated COX‐2 induction. The effect of ESE‐1 on the COX‐2 promoter is further enhanced by cooperation with other transcription factors such as nuclear factor‐κB and nuclear factor of activated T cells. Neutralization of COX‐2 is the goal of many anti‐inflammatory drugs. As an activator of COX‐2 induction, ESE‐1 may become a target for such therapeutics as well. Together with our previous reports of the role of ESE‐1 as an inducer of nitric oxide synthase in endothelial cells and as a mediator of pro‐inflammatory cytokines in vascular and connective tissue cells, these results establish ESE‐1 as an important player in the regulation of inflammation.
Bioinformatic and enzymatic characterization of the MAPEG superfamily
Authors: Bresell Anders , Weinander Rolf , Lundqvist Gerd , Raza Haider , Shimoji Miyuki , Sun Tie‐Hua , Balk Lennart , Wiklund Ronney , Eriksson Jan , Jansson Christer , Persson Bengt , Jakobsson Per‐Johan , Morgenstern Ralf
Published: March 2005

The membrane associated proteins in eicosanoid and glutathione metabolism (MAPEG) superfamily includes structurally related membrane proteins with diverse functions of widespread origin. A total of 136 proteins belonging to the MAPEG superfamily were found in database and genome screenings. The members were found in prokaryotes and eukaryotes, but not in any archaeal organism. Multiple sequence alignments and calculations of evolutionary trees revealed a clear subdivision of the eukaryotic MAPEG members, corresponding to the six families of microsomal glutathione transferases (MGST) 1, 2 and 3, leukotriene C4 synthase (LTC4), 5‐lipoxygenase activating protein (FLAP), and prostaglandin E synthase. Prokaryotes contain at least two distinct potential ancestral subfamilies, of which one is unique, whereas the other most closely resembles enzymes that belong to the MGST2/FLAP/LTC4 synthase families. The insect members are most similar to MGST1/prostaglandin E synthase. With the new data available, we observe that fish enzymes are present in all six families, showing an early origin for MAPEG family differentiation. Thus, the evolutionary origins and relationships of the MAPEG superfamily can be defined, including distinct sequence patterns characteristic for each of the subfamilies. We have further investigated and functionally characterized representative gene products from Escherichia coli, Synechocystis sp., Arabidopsis thaliana and Drosophila melanogaster, and the fish liver enzyme, purified from pike (Esox lucius). Protein overexpression and enzyme activity analysis demonstrated that all proteins catalyzed the conjugation of 1‐chloro‐2,4‐dinitrobenzene with reduced glutathione. The E. coli protein displayed glutathione transferase activity of 0.11 µmol·min−1·mg−1 in the membrane fraction from bacteria overexpressing the protein. Partial purification of the Synechocystis sp. protein yielded an enzyme of the expected molecular mass and an N‐terminal amino acid sequence that was at least 50% pure, with a specific activity towards 1‐chloro‐2,4‐dinitrobenzene of 11 µmol·min−1·mg−1. Yeast microsomes expressing the Arabidopsis enzyme showed an activity of 0.02 µmol·min−1·mg−1, whereas the Drosophila enzyme expressed in E. coli was highly active at 3.6 µmol·min−1·mg−1. The purified pike enzyme is the most active MGST described so far with a specific activity of 285 µmol·min−1·mg−1. Drosophila and pike enzymes also displayed glutathione peroxidase activity towards cumene hydroperoxide (0.4 and 2.2 µmol·min−1·mg−1, respectively). Glutathione transferase activity can thus be regarded as a common denominator for a majority of MAPEG members throughout the kingdoms of life whereas glutathione peroxidase activity occurs in representatives from the MGST1, 2 and 3 and PGES subfamilies.
Silencing the expression of mitochondrial acyl‐CoA thioesterase I and acyl‐CoA synthetase 4 inhibits hormone‐induced steroidogenesis
Authors: Maloberti Paula , Castilla Rocío , Castillo Fernanda , Maciel Fabiana Cornejo , Mendez Carlos F. , Paz Cristina , Podestá Ernesto J.
Published: March 2005

Arachidonic acid and its lypoxygenated metabolites play a fundamental role in the hormonal regulation of steroidogenesis. Reduction in the expression of the mitochondrial acyl‐CoA thioesterase (MTE‐I) by antisense or small interfering RNA (siRNA) and of the arachidonic acid‐preferring acyl‐CoA synthetase (ACS4) by siRNA produced a marked reduction in steroid output of cAMP‐stimulated Leydig cells. This effect was blunted by a permeable analog of cholesterol that bypasses the rate‐limiting step in steroidogenesis, the transport of cholesterol from the outer to the inner mitochondrial membrane. The inhibition of steroidogenesis was overcome by addition of exogenous arachidonic acid, indicating that the enzymes are part of the mechanism responsible for arachidonic acid release involved in steroidogenesis. Knocking down the expression of MTE‐I leads to a significant reduction in the expression of steroidogenic acute regulatory protein. This protein is induced by arachidonic acid and controls the rate‐limiting step. Overexpression of MTE‐I resulted in an increase in cAMP‐induced steroidogenesis. In summary, our results demonstrate a critical role for ACS4 and MTE‐I in the hormonal regulation of steroidogenesis as a new pathway of arachidonic acid release different from the classical phospholipase A2 cascade.
Optimal Module Selection for Preliminary Design of Reconfigurable Machine Tools
Authors: Chen Li , Xi Fengfeng (Jeff) , Macwan Ashish
Published: March 2005

Presented in this paper is a feature-based method for selecting an optimal (minimum yet sufficient) set of modules necessary to form a reconfigurable machine tool for producing a part family. This method consists of two parts. In the first part, a feature-module database is created to form a selection space, where the machinable geometric features identified in STEP are defined as functional requirements (FR’s) and the structural component modules derived from the conventional machine tools as design parameters (DP’s). An inner FR-to-DP mapping mechanism within the database is based on the “Membership Grade Matrix,” which defines metrics to quantify the degree of association between a FR and a DP. Within the confines of the selection space built upon this FR-DP database, the second part of the method involves a two-step procedure for module selection. The first step is to select the modules from this space to construct all the required individual configurations of the reconfigurable machine tool. The second step is to maximize the number of common modules among the originally selected modules through re-selection. A case study on designing a reconfigurable machine tool dedicated to a given family of die molds is conducted and discussed.
Modeling of Workpiece Location Error Due to Fixture Geometric Error and Fixture-Workpiece Compliance
Authors: Raghu Anand , Melkote Shreyes N.
Published: March 2005

Several fixture-related error sources contribute to workpiece location error in a machining system. Inaccurate part placement in the fixture relative to the cutting tool, for example, can negatively affect the quality of the part. In this paper, the following major sources of error are considered: fixture geometric error and elastic deformation of the fixture and workpiece due to fixturing forces. The workpiece location error is predicted by modeling the process of part loading (given fixture geometric variations) and clamping (given deformations at the contact points) in a machining fixture. Linear elastic models for the fixture elements, contact mechanics models for the contact regions, and flexibility influence coefficients to capture the bulk elasticity of the workpiece have been used to model the compliance of the entire fixture-workpiece system. The deformations at the contact points are obtained by solving a constrained optimization model. The effect of geometric errors and compliance on workpiece location error is examined using part response points as a measure of quality. Experimental validation is also provided for several fixture-workpiece variable levels using a 3-2-1 machining fixture.
Failure Analysis of Rapid Prototyped Tooling in Sheet Metal Forming—V-Die Bending
Authors: Park Y. , Colton J. S.
Published: March 2005

The demand for rapid, low-cost die fabrication and modification technology is greater than ever in the sheet metal forming industry. One category of rapid tooling technology involves the use of advanced polymers and composite materials to fabricate metal forming dies. However, due to their lack of strength as compared to conventional metal dies, the use of polymer dies is often limited to prototype or short-run production. In addition, because the mechanisms by which they fail are not fully understood, the dies are designed on the basis of experience and intuition. This study investigates the failure of V-bending dies fabricated from an easy-to-machine, polyurethane-based, composite board stock. Based on the mechanical behavior of the die material, several failure criteria are proposed to predict die failure mode and the corresponding die life. Both computational and experimental methods are employed to assess the accuracy of the criteria and to identify the dominant process parameters in V-die bending.
Failure Analysis of Rapid Prototyped Tooling in Sheet Metal Forming—Cylindrical Cup Drawing
Authors: Park Y. , Colton J. S.
Published: March 2005

This paper presents a failure analysis of cylindrical cup drawing dies machined from a polymer composite rapid tooling material. Cup drawing is a complicated process, involving both bending and stretching. In this study, possible die failure modes are identified experimentally. Finite element analyses (FEA) are performed to obtain the stress–strain responses, which are used to determine the dominant failure mode. As cup drawing involves interactions among process parameters, the statistical design of experiments is employed to perform a parametric study. The resulting die failure mode estimation method is verified through experiments.
Incorporation of Sheet-Forming Effects in Crash Simulations Using Ideal Forming Theory and Hybrid Membrane and Shell Method
Authors: Ryou Hansun , Chung Kwansoo , Yoon Jeong-Whan , Han Chung-Souk , Ryoun Youn Jae , Kang Tae Jin
Published: March 2005

In order to achieve reliable but cost-effective crash simulations of stamped parts, sheet-forming process effects were incorporated in simulations using the ideal forming theory mixed with the three-dimensional hybrid membrane and shell method, while the subsequent crash simulations were carried out using a dynamic explicit finite element code. Example solutions performed for forming and crash simulations of I- and S-shaped rails verified that the proposed approach is cost effective without sacrificing accuracy. The method required a significantly small amount of additional computation time, less than 3% for the specific examples, to incorporate sheet-forming effects into crash simulations. As for the constitutive equation, the combined isotropic-kinematic hardening law and the nonquadratic anisotropic yield stress potential as well as its conjugate strain-rate potential were used to describe the anisotropy of AA6111-T4 aluminum alloy sheets.
Functional Filtering and Performance Correlation of Plateau Honed Surface Profiles
Authors: Muralikrishnan B. , Raja J.
Published: March 2005

Plateau honing produces a unique texture on cylinder liner surface. This surface is engineered to simulate the actual running in process of the engine and results in a core layer superimposed on valleys. Because of the complex nature of the surface, characterization of such surfaces is very different from traditional surface texture analysis. Different filtering techniques have been employed to remove waviness from these profiles. Parameters are subsequently computed from the bearing area curve of the roughness profile. With recent progress in filtering of surface profiles, we propose a functional analysis approach based on morphological filters. The advantage of this technique is the clear separation of the core texture from the valleys resulting in better correlation with process and functional measures. A number of profiles are collected from two sets of liners with different performance characteristics. A cause effect model is built and used for performance prediction.
Press Tonnage Signal Decomposition and Validation Analysis for Transfer or Progressive Die Processes
Authors: Jin Jionghua , Shi Jianjun
Published: March 2005

A transfer or progressive die process consists of multiple stations working simultaneously in each stroke. This paper aims to develop a new methodology that can decompose press tonnage signals to obtain individual station signals without using in-die sensors. In the paper, two different tonnage decomposition tests, as well as the associated data analysis algorithms, are developed. Statistical profile analyses and an in-die sensor test were conducted to validate the proposed methodology.
Optimum Design of Fatigue Strength of a Cold Extrusion Compound Container
Authors: Luo and Zhonghua , Zhang Zhiliang
Published: March 2005

This technical brief discusses optimum design of a cold extrusion compound container. First, the formulae of stresses for each component in the container and of shrink-fit pressure are derived. Next, the fatigue strength theory of the container is described by means of the Sines’ method. Finally, mathematical models of optimum design of fatigue strength are established for monobloc, two-piece, and three-piece containers, and the following two results are obtained: (i) the maximal load capacities of two- and three-piece containers are, respectively, 1.89 and 2.04 times that of a monobloc container, and (ii) it is not necessary to design compound containers with outer radii larger than 4 times their inner radii.
Interfacial Adhesion of Anisotropic Conductive Adhesives on Polyimide Substrate
Authors: Cao Liqiang , Lai Zonghe , Liu Johan
Published: March 2005

There has been steadily increasing interest in using electrically conductive adhesives as interconnecting materials in electronics manufacturing. Simple processing, low processing temperature and fine pitch capability are the major advantages of conducting adhesive technology. A new and innovative connection technology geared towards achieving increased functionality at a lower total system cost is anisotropic conductive adhesive (ACA) interconnection. ACAs, when used for flip chip assembly, provide electrical as well as mechanical interconnections for fine pitch applications. This work deals with adhesion issues between ACA on polyimide materials. The paper presents a reliability assessment of adhesive joints using ACA on polyimide substrate that was conducted by testing samples at various aging temperature, high humidity and high pressure environments. The effects of high temperature and high humidity on the bond strength of ACA joints were measured using 90 deg peel test as well as by microstructural examination. It was found that aging generally caused a decrease in peel strength, especially the results of scanning electronic microscopy showed that the pressure cooker test could most effectively reveal the adhesion behavior.
Thermal Design and Optimization Methodology for Integrated Power Electronics Modules
Authors: Pang Ying Feng , Scott Elaine P. , Chen Jonah Zhou , Thole Karen A.
Published: March 2005

A methodology was developed and implemented to optimize the design layout for i_ntegrated p_ower e_lectronics m_odules (IPEMs) by considering both the electrical and thermal performances. This paper is primarily focused on the thermal aspects, which were analyzed using three-dimensional (3D) computational software tools. Implementation of the design methodology resulted in a 70 percent reduction in the common mode current, a 4 percent reduction in the size of the geometric footprint, and a 7°C reduction in the maximum temperature rise for the case studied, thus, providing an increase in the IPEM’s overall performance.
Flow Past a Spinning Sphere With Surface Blowing and Heat Transfer
Authors: Niazmand H. , Renksizbulut M.
Published: March 2005

Computations are performed to determine the transient three-dimensional heat transfer rates and fluid forces acting on a stream-wise spinning sphere for Reynolds numbers in the range 10⩽Re⩽300 and angular velocities Ωx⩽2. In this Re range, classical flow past a solid sphere develops four different flow regimes, and the effects of particle spin are studied in each regime. Furthermore, the combined effects of particle spin and surface blowing are examined. Sphere spin increases drag in all flow regimes, while lift shows a nonmonotonic behavior. Heat transfer rates are not influenced by spin up to a certain Ωx but increase monotonically thereafter. An interesting feature associated with sphere spin is the development of a special wake regime such that the wake simply spins without temporal variations in its shape. For this flow condition, the magnitudes of the lift, drag, and heat transfer coefficients remain constant in time. Correlations are provided for drag and heat transfer.
Velocity Field Reconstruction in the Mixing Region of Swirl Sprays Using General Regression Neural Network
Authors: Ghorbanian K. , Soltani M. R. , Morad M. R. , Ashjaee M.
Published: March 2005

A general regression neural network technique is proposed for design optimization of pressure-swirl injectors. Phase doppler anemometry measurements for velocity distributions are used to train the neural network. An overall optimized value for the width of the probability is determined. The velocity field in the extrapolation regime is reconstructed with an accuracy of 93%. Excellent agreement between the predicted values and the measurements is obtained. The results indicate that the capability of performing design- and optimization studies for pressure-swirl injectors with sufficient accuracy exists by applying modest amount of data in conjunction with an overall optimized value for the width of the probability.
A Mixed-Time-Scale SGS Model With Fixed Model-Parameters for Practical LES
Authors: Inagaki Masahide , Kondoh Tsuguo , Nagano Yasutaka
Published: March 2005

A new subgrid-scale (SGS) model for practical large eddy simulation (LES) is proposed. The model is constructed with the concept of mixed time-scale, which makes it possible to use fixed model-parameters and to dispense with the distance from the wall. The model performance is tested in plane channel flows, and the results show that this model is able to account for near-wall turbulence without an explicit damping function as in the dynamic Smagorinsky model. The model is also evaluated in a backward-facing step flow and in a flow around a circular cylinder. The calculated results using the consistent model-parameters show good agreement with experimental data, while the results obtained using the dynamic Smagorinsky model show less accuracy and less computational stability. Furthermore, to confirm the validity of the present model in practical applications, the three-dimensional complex flow around a bluff body (Ahmed et al., SAE paper no. 840300) is also calculated with the model. The agreement between the calculated results and the experimental data is quite satisfactory. These results suggest that the present model is a refined SGS model suited for practical LES to compute flows in a complicated geometry.
Immiscible Liquid-Liquid Displacement in Capillary Tubes
Authors: Soares E. J. , Carvalho M. S. , Mendes P. R. Souza
Published: March 2005

We analyze the liquid-liquid displacement in capillary tubes. The goal is to determine the amount of displaced liquid that remains attached to the tube wall and the configuration of the liquid-liquid interface at different operating parameters. The study encompasses both numerical and experimental approaches. The finite element method is used to solve the governing equations and, in order to validate the predictions, visualization experiments are performed to capture images of the interface. The numerical results were obtained for the assumption of negligible inertia, and the effects of viscosity ratio and capillary number are investigated. The predictions and experimental observations are in good agreement.
Nonlinear Hydrodynamic Forces on an Accelerated Body in Waves
Authors: Yoshida Motoki , Kinoshita Takeshi , Bao Weiguang
Published: March 2005

Wave-drift added mass results from nonlinear interactions between waves and low-frequency oscillatory motions of a floating body, in the presence of incident waves. In previous works, wave-drift damping which is the component of wave-drift force in phase with the velocity of low-frequency oscillations was investigated mainly based on a quasi-steady analysis. However, investigations related to wave-drift added mass, the component in phase with acceleration, were very few. In this paper, wave-drift added mass is derived directly from a perturbation analysis with two small parameters and two time scales, using a Cartesian coordinate system that follows the low-frequency oscillations, dynamic oscillation model has been used. Especially, the method to solve higher-order potentials, which are necessary for evaluation of wave-drift added mass, is presented. Analytical solutions and calculated results of wave-drift added mass, and far field radiation conditions for each order of potentials are obtained. Also, wave-drift added mass of floating bodies has been systematically measured from a slowly forced oscillation test or a free decay test in waves. Experimental results are compared with calculated results. Then, for a supplement, the secular behavior that some velocity potentials show is discussed. Applying a multiple scale perturbation analysis to one of these problems, a nonsecular solution is obtained.
ARTHROSCOPIC RESECTION OF WRIST GANGLIA
Authors: Mathoulin C. , Hoyos A. , Pelaez J.
Published: March 2005

The arthroscopic resection of synovial cysts of the wrist is a simple technique which is comfortable for the patient. We report on a series of 96 patients with dorsal synovial cysts (75 women, 21 men). All patients had undergone preliminary treatment which had been unsuccessful. We operated on 32 patients with a volar cyst (27 women, five men). All the patients were operated on as outpatients under local regional anaesthesia. For the dorsal cysts, after having precisely located the cyst, it is then resected after having inserted a shaver directly through the wall of the cyst starting with the capsule. For the volar cysts the arthroscope was inserted through a 3-4 portal and the shaver was inserted through a 1-2 radiocarpal portal. In all cases, there was no immobilisation and a range of motion was started the same day. For the dorsal cysts, our average follow-up was 34 months (range 12–46 months). There were no complications. We had four recurrences. For the palmar cysts, our average follow-up was 26 months (range 12–39 months). There have been no recurrences to date.
THE INFLUENCE OF MOTOR AXON MISDIRECTION ON MUSCLE CONTRACTION FORCE IN EARLY NERVE REPAIR IN A RAT SCIATIC NERVE MODEL
Authors: Koizumi Masahiro , Maki Yutaka , Yoshizu Takae , Tsubokawa Naoto
Published: March 2005

We examined the influence of misdirection of regenerating motor axons toward the distal sensory Schwann tubes on the muscle contraction force in early nerve repair using a rat sciatic nerve model. At 0, 1, 2, 4 and 8 weeks after severing the tibial, peroneal and sural nerves, the proximal stump of the tibial nerve was anastomosed with the distal stumps of both the peroneal and sural nerves using tubulisation (n=10 in each of five groups). We intentionally used the distal stump of the sural nerve (a sensory nerve) to induce regeneration in motor axons from the proximal tibial nerve stump toward the distal sensory nerve stump. Twenty-four weeks after nerve repair, isometric contraction force and wet weight of the anterior tibial muscle were measured, and the numbers of regenerated myelinated axons (motor and sensory) in the distal sural and peroneal nerves were counted. The rates of sural nerve regeneration were significantly higher at weeks 0 and 1 than at the later repair times. However, muscle contraction force and muscle wet weight did not differ significantly between groups in which nerves were repaired within four weeks of severance. These results indicate that peripheral nerve repair within four weeks of severance does not influence the muscle contraction force of single muscle despite the misdirection of motor axons toward the distal sensory Schwann tubes.
"LIFE" ABOVE THE NECK: BRAIN TUMOUR PRESENTING AS CARPAL TUNNEL SYNDROME
Authors: Dunkow P. D. , Bhutta Aqeel , Pena M. A.
Published: March 2005

Carpal tunnel syndrome is a common condition with many aetiologies. We present a case report of a glioblastoma which presented as carpal tunnel syndrome, and highlights that the most proximal site for pathology is not the spinal cord.
ENDOSCOPIC CARPAL TUNNEL RELEASE FOR RECURRENT CARPAL TUNNEL SYNDROME AFTER PREVIOUS OPEN RELEASE
Authors: Teoh Lam Chuan , Tan Puay Ling
Published: March 2005

Recurrent carpal tunnel syndrome from various causes has been shown to occur in up to 19% of patients. Endoscopic carpal tunnel release has been used to decompress the median nerve in carpal tunnel syndrome for many years. However, endoscopic release for recurrent carpal tunnel syndrome after previous surgical release has not been reported. Nine hands in six patients had recurrent carpal tunnel syndrome five to 20 years after previous open carpal tunnel release. All the cases were successfully treated with endoscopic release.
SUICIDAL MERCURY INJECTION INTO THE UPPER LIMB: A CASE STUDY
Authors: Wong F. , Hung L. K. , Wong C. H. , Ho P. C.
Published: March 2005

We report a rare case of self-injection of mercury into the subcutaneous tissue of the upper limb. A multi-disciplinary management approach was adopted including cooperation between toxicologists, orthopaedic surgeons, radiologists and environment safety personnel. Surgical removal of mercury under radiological screening and systemic intoxication treated by chelating agents, namely dimercaprol and succimer. Serial serum and urine mercury levels showed an initial rise despite surgical removal and returned to normal after a prolonged period of time. Safety precautions were taken during surgery to avoid inadvertent intoxication of staff. Contamination of the operation theatre was monitored by the amount of mercury vapour released into the air. All personnels involved in the management of the patient did not show any evidence of mercury intoxication.
Inhibition of calpain blocks pancreatic β-cell spreading and insulin secretion
Authors: Parnaud Géraldine , Hammar Eva , Rouiller Dominique G. , Bosco Domenico
Published: March 2005

In addition to promoting insulin secretion, an increase in cytosolic Ca2+triggered by glucose has been shown to be crucial for spreading of β-cells attached on extracellular matrix (804G matrix). Calpains are Ca2+-dependent cysteine proteases involved in an extended spectrum of cellular responses, including cytoskeletal rearrangements and vesicular trafficking. The present work aimed to assess whether calpain is also implicated in the process of Ca2+-induced insulin secretion and spreading of rat pancreatic β-cells. The results indicate calpain dependency of β-cell spreading on 804G matrix. Indeed, treatment with three distinct calpain inhibitors (N-Ac-Leu-Leu-norleucinal, calpeptin, and ethyl(+)-(2S,3S)-3-[(S)-3-methyl-1-(3-methylbutylcarbamoyl)butyl-carbamoyl]-2-ox-iranecarboxylate) inhibited cell spreading induced by glucose and KCl, whereas cell attachment was not significantly modified. Calpain inhibitors also suppressed glucose- and KCl-stimulated insulin secretion without affecting insulin synthesis. Washing the inhibitor out of the cell culture restored spreading on 804G matrix and insulin secretory response after 24 h. In addition, incubation with calpeptin did not affect insulin secretory response to mastoparan that acts on exocytosis downstream of intracellular calcium [Ca2+]i. Finally, calpeptin was shown to affect the [Ca2+]iresponse to glucose but not to KCl. In summary, the results show that inhibition of calpain blocks spreading and insulin secretion of primary pancreatic β-cells. It is therefore suggested that calpain could be a mediator of Ca2+-induced-insulin secretion and β-cell spreading.
Increasing mammalian cardiomyocyte contractility with residues identified in trout troponin C
Authors: Gillis Todd E. , Liang Bo , Chung Franca , Tibbits Glen F.
Published: March 2005

The Ca2+ sensitivity of force generation in trout cardiac myocytes is significantly greater than that from mammalian hearts. One mechanism that we have suggested to be responsible, at least in part, for this high Ca2+ sensitivity is the isoform of cardiac troponin C (cTnC) found in trout hearts (ScTnC), which has greater than twice the Ca2+ affinity of mammalian cTnC (McTnC). Here, through a series of mutations, the residues in ScTnC responsible for its high Ca2+ affinity have been identified as being Asn2, Ile28, Gln29, and Asp30. When these residues in McTnC were mutated to the trout-equivalent amino acid, the Ca2+ affinity of the molecule, determined by monitoring the fluorescence of a Trp inserted for a Phe at residue 27, is comparable to that of ScTnC. To determine how a McTnC mutant containing Asn2, Ile28, Gln29, and Asp30 (NIQD McTnC) affects the Ca2+ sensitivity of force generation, endogenous cTnC in single, chemically skinned rabbit cardiomyocytes was replaced with either wild-type McTnC or NIQD McTnC. Our results demonstrate that the cardiomyocytes containing NIQD McTnC were approximately twice as sensitive to Ca2+, illustrating that a McTnC mutant with similar Ca2+ affinity as ScTnC can be used to sensitize mammalian cardiac myocytes to Ca2+.
Small interfering RNA-mediated functional silencing of vasopressin V2receptors in the mouse kidney
Authors: Hassan Ali , Tian Ying , Zheng Wei , Ji Hong , Sandberg Kathryn , Verbalis Joseph G.
Published: March 2005

The antidiuretic effects of arginine vasopressin (AVP) on the kidney are mediated by V2subtype AVP receptors (V2R). To investigate the role of regulation of V2R in water and sodium homeostasis, we have developed a method for small interfering RNA (siRNA)-mediated inhibition of V2R expression in vivo. Three 21-nt siRNA sequences were chosen that specifically targeted the mouse V2R but shared no appreciable sequence homology to any other known mouse genes, including the vasopressin V1aand V1breceptors. Additionally, an siRNA sequence that shared no significant matches to any known mammalian gene sequences was chosen for use as a control. Chemically synthesized siRNA was complexed with the liposomal transfection reagent DOTAP. Each mouse (male C57BL/6) received 3.6 nmol (∼50 μg) of either the control (nonsilencing) or one of the V2R-targeting siRNAs via intravenous injection. Forty-eight hours after injection membranes were prepared from the inner medulla of the kidneys, and V2R expression was measured by a radioligand binding assay and Western immunoblotting. Treatment with one of the V2R-targeting siRNAs (R2) caused a 39.7 ± 8.7% reduction in V2R-specific binding compared with the control ( n = 11, P < 0.05) and a 37.0 ± 2.3% reduction in V2R protein expression as measured by Western immunoblotting ( n = 4, P < 0.001). Additionally, real-time PCR revealed that R2 siRNA treatment induced a 68.8 ± 2.2% reduction in V2R mRNA. However, this siRNA treatment did not alter the animals’ basal urine concentrating capacity under unstimulated conditions. In subsequent experiments, treatment with R2 siRNA was found to significantly attenuate the antidiuretic effects the V2R-specific AVP agonist 1-desamino-[8-d-arginine]vasopressin (dDAVP). Mice were infused with dDAVP (0.25 ng/h) for 3 days to produce maximal antidiuresis and then were injected with either the R2 siRNA or the nonsilencing control. On day 2 after treatment, urine osmolality was significantly decreased from 3,455 ± 72 in control animals ( n = 12) to 3,155 ± 129 mosmol/kgH2O in R2 siRNA-treated animals ( n = 12) ( P < 0.05); similarly, on day 2 24-h urine volume was significantly increased from 0.86 ± 0.07 ml/day to 1.11 ± 0.06 ml/day in R2 siRNA-treated animals ( P < 0.05). In summary we have demonstrated that RNA interference methodology can be used successfully in vivo to significantly reduce functional expression of the V2R in the mouse kidney.
Identification of genes expressed differentially in subcutaneous and visceral fat of cattle, pig, and mouse
Authors: Hishikawa Daisuke , Hong Yeon-Hee , Roh Sang-gun , Miyahara Hisae , Nishimura Yukihiko , Tomimatsu Ai , Tsuzuki Hiroaki , Gotoh Chizu , Kuno Masaaki , Choi Ki-Choon , Lee Hong-gu , Cho Kwang-keun , Hidari Hisashi , Sasaki Shinichi
Published: March 2005

The factors that control fat deposition in adipose tissues are poorly understood. It is known that visceral adipose tissues display a range of biochemical properties that distinguish them from adipose tissues of subcutaneous origin. However, we have little information on gene expression, either in relation to fat deposition or on interspecies variation in fat deposition. The first step in this study was to identify genes expressed in fat depot of cattle using the differential display RT-PCR method. Among the transcripts identified as having differential expression in the two adipose tissues were cell division cycle 42 homolog (CDC42), prefoldin-5, decorin, phosphate carrier, 12S ribosomal RNA gene, and kelch repeat and BTB domain containing 2 (Kbtbd2). In subsequent experiments, we determined the expression levels of these latter genes in the pig and in mice fed either a control or high-fat diet to compare the regulation of fat accumulation in other animal species. The levels of CDC42 and decorin mRNA were found to be higher in visceral adipose tissue than in subcutaneous adipose tissue in cattle, pig, and mice. However, the other genes studied did not show consistent expression patterns between the two tissues in cattle, pigs, and mice. Interestingly, all genes were upregulated in subcutaneous and/or visceral adipose tissues of mice fed the high-fat diet compared with the control diet. The data presented here extend our understanding of gene expression in fat depots and provide further proof that the mechanisms of fat accumulation differ significantly between animal species.
Identification of human exons overexpressed in tumors through the use of genome and expressed sequence data
Authors: Kirschbaum-Slager Natanja , Parmigiani Raphael Bessa , Camargo Anamaria Aranha , de Souza Sandro José
Published: March 2005

Alternative splicing is one of the major sources of the large transcriptional diversity found in human cells. Splicing variants have been shown to be associated with features like spreading and progression in several human tumors. Therefore, such variants may be of great importance as both diagnostic and therapeutic tools. Here, by using a set of criteria regarding the expression pattern of splicing variants and statistical analyses, we were able to screen the genome for exons overexpressed in tumors of specific tissues. However, as in other analyses attempting to identify tumor-associated variants, our list of candidates was seriously inflated with cases of genes differentially expressed in tumors. To exclude these cases and increase the probability of finding bona fide regulated splicing variants, we performed a serial analysis of gene expression (SAGE), excluding those genes that were shown to be upregulated in tumors. This allowed us to predict the overexpression of single exons in specific tumors. Our final group of candidates includes 1,386 exons belonging to 638 genes. Experimental validation of a few candidates in normal tissue, tumor cell lines, and patient samples suggests that most of these candidates are indeed tumor-associated exons. Further functional classification of our candidate genes shows that our final list is slightly inflated with cancer-related genes.
Molecular Physiology and Pathophysiology of Electroneutral Cation-Chloride Cotransporters
Authors: Gamba Gerardo
Published: March 2005

Electroneutral cation-Cl−cotransporters compose a family of solute carriers in which cation (Na+or K+) movement through the plasma membrane is always accompanied by Cl−in a 1:1 stoichiometry. Seven well-characterized members include one gene encoding the thiazide-sensitive Na+−Cl−cotransporter, two genes encoding loop diuretic-sensitive Na+−K+−2Cl−cotransporters, and four genes encoding K+−Cl−cotransporters. These membrane proteins are involved in several physiological activities including transepithelial ion absorption and secretion, cell volume regulation, and setting intracellular Cl−concentration below or above its electrochemical potential equilibrium. In addition, members of this family play an important role in cardiovascular and neuronal pharmacology and pathophysiology. Some of these cotransporters serve as targets for loop diuretics and thiazide-type diuretics, which are among the most commonly prescribed drugs in the world, and inactivating mutations of three members of the family cause inherited diseases such as Bartter's, Gitelman's, and Anderman's diseases. Major advances have been made in the past decade as consequences of molecular identification of all members in this family. This work is a comprehensive review of the knowledge that has evolved in this area and includes molecular biology of each gene, functional properties of identified cotransporters, structure-function relationships, and physiological and pathophysiological roles of each cotransporter.
Adult Neurogenesis: From Precursors to Network and Physiology
Authors: Abrous Djoher Nora , Koehl Muriel , Le Moal Michel
Published: March 2005

The discovery that the adult mammalian brain creates new neurons from pools of stemlike cells was a breakthrough in neuroscience. Interestingly, this particular new form of structural brain plasticity seems specific to discrete brain regions, and most investigations concern the subventricular zone (SVZ) and the dentate gyrus (DG) of the hippocampal formation (HF). Overall, two main lines of research have emerged over the last two decades: the first aims to understand the fundamental biological properties of neural stemlike cells (and their progeny) and the integration of the newly born neurons into preexisting networks, while the second focuses on understanding its relevance in brain functioning, which has been more extensively approached in the DG. Here, we propose an overview of the current knowledge on adult neurogenesis and its functional relevance for the adult brain. We first present an analysis of the methodological issues that have hampered progress in this field and describe the main neurogenic sites with their specificities. We will see that despite considerable progress, the levels of anatomic and functional integration of the newly born neurons within the host circuitry have yet to be elucidated. Then the intracellular mechanisms controlling neuronal fate are presented briefly, along with the extrinsic factors that regulate adult neurogenesis. We will see that a growing list of epigenetic factors that display a specificity of action depending on the neurogenic site under consideration has been identified. Finally, we review the progress accomplished in implicating neurogenesis in hippocampal functioning under physiological conditions and in the development of hippocampal-related pathologies such as epilepsy, mood disorders, and addiction. This constitutes a necessary step in promoting the development of therapeutic strategies.
Links Between Dietary Salt Intake, Renal Salt Handling, Blood Pressure, and Cardiovascular Diseases
Authors: Meneton Pierre , Jeunemaitre Xavier , de Wardener Hugh E. , Macgregor Graham A.
Published: March 2005

Epidemiological, migration, intervention, and genetic studies in humans and animals provide very strong evidence of a causal link between high salt intake and high blood pressure. The mechanisms by which dietary salt increases arterial pressure are not fully understood, but they seem related to the inability of the kidneys to excrete large amounts of salt. From an evolutionary viewpoint, the human species is adapted to ingest and excrete <1 g of salt per day, at least 10 times less than the average values currently observed in industrialized and urbanized countries. Independent of the rise in blood pressure, dietary salt also increases cardiac left ventricular mass, arterial thickness and stiffness, the incidence of strokes, and the severity of cardiac failure. Thus chronic exposure to a high-salt diet appears to be a major factor involved in the frequent occurrence of hypertension and cardiovascular diseases in human populations.
A Strategy for Early Detection of Recurrent Hepatocellular Carcinoma following Initial Remission by Transcatheter Arterial Chemoembolization
Authors: Chung Young-Hwa
Published: March 2005

Objectives: To find a better surveillance method in detecting recurrent HCCs, patterns of recurrences following initial remission by transcatheter arterial chemoembolization (TACE) were evaluated. Methods: Of 235 consecutive HCC patients who underwent TACE, 69 with initial remission were followed for >12 months. We compared the recurrence rates according to the characteristics of original HCCs and analyzed the locations of recurrent HCCs. We also evaluated the diagnostic efficacies of CT scan with serum AFP, angiography and Lipiodol CT scan in detecting recurrent HCCs. Results: In 37 of 69, recurrent HCCs were detected after a median period of 17 months. Multinodular HCCs recurred more frequently than single-nodular HCCs. All of 5 patients with portal vein thrombosis recurred. Although 46% of recurrences were adjacent to original tumors, 62% were separated from them (8% at both). HCC with heterogeneous lipiodol uptake frequently recurred adjacent to original tumors. Only 18 of 37 recurrent HCCs were initially detected by serum AFP and CT scans; 17 by angiography, 2 only by lipiodol CT scan. Conclusions: Regular angiography may be valuable in detecting recurrent HCCs, especially in multinodular HCC. HCC with heterogeneous lipiodol uptake should be treated in combination with local ablation therapy.