bluuebunny/crossref_metadata_2025 huggingface dataset:
Opposite effects of Ni2+ on Xenopus and rat ENaCs expressed in Xenopus oocytes
Authors: Cucu Dana , Simaels Jeannine , Eggermont Jan , Van Driessche Willy , Zeiske Wolfgang
Published: June 2005

Opposite effects of Ni2+ on Xenopus and rat ENaCs expressed in Xenopus oocytes. Am J Physiol Cell Physiol 289: C946–C958, 2005. First published June 8, 2005; .—The epithelial Na+ channel (ENaC) is modulated by various extracellular factors, including Na+, organic or inorganic cations, and serine proteases. To identify the effect of the divalent Ni2+ cation on ENaCs, we compared the Na+ permeability and amiloride kinetics of Xenopus ENaCs (xENaCs) and rat ENaCs (rENaCs) heterologously expressed in Xenopus oocytes. We found that the channel cloned from the kidney of the clawed toad Xenopus laevis [wild-type (WT) xENaC] was stimulated by external Ni2+, whereas the divalent cation inhibited the channel cloned from the rat colon (WT rENaC). The kinetics of amiloride binding were determined using noise analysis of blocker-induced fluctuation in current adapted for the transoocyte voltage-clamp method, and Na+ conductance was assessed using the dual electrode voltage-clamp (TEVC) technique. The inhibitory effect of Ni2+ on amiloride binding is not species dependent, because Ni2+ decreased the affinity (mainly reducing the association rate constant) of the blocker in both species in competition with Na+. Importantly, using the TEVC method, we found a prominent difference in channel conductance at hyperpolarizing voltage pulses. In WT xENaCs, the initial ohmic current response was stimulated by Ni2+, whereas the secondary voltage-activated current component remained unaffected. In WT rENaCs, only a voltage-dependent block by Ni2+ was obtained. To further study the origin of the xENaC stimulation by Ni2+, and based on the rationale of the well-known high affinity of Ni2+ for histidine residues, we designed α-subunit mutants of xENaCs by substituting histidines that were expressed in oocytes, together with WT β- and γ-subunits. Changing His215 to Asp in one putative amiloride-binding domain (WYRFHY) in the extracellular loop between Na+ channel membrane segments M1 and M2 had no influence on the stimulatory effect of Ni2+, and neither did complete deletion of this segment. Next, we mutated His416 flanked by His411 and Cys417, a unique site for possible heavy metal ion chelation, and, with this quality, most proximal (∼100 amino acids upstream of the second putative amiloride binding site at the pore entrance), was found localized at M2. Replacing His416 with arginine, aspartate, tyrosine, and alanine clearly affected amiloride binding in all cases, as well as Na+ conductance, as expressed in the xENaC current-voltage relationship, especially with regard to aspartate and tyrosine. However, similarly to those obtained with the WYRFHY stretch, none of these mutations could either abolish the stimulating effect of Ni2+ or reverse it to an inhibitory type.
Variability of Swallowing Performance in Intact, Freely FeedingAplysia
Authors: Lum Cecilia S. , Zhurov Yuriy , Cropper Elizabeth C. , Weiss Klaudiusz R. , Brezina Vladimir
Published: June 2005

Variability in nervous systems is often taken to be merely “noise.” Yet in some cases it may play a positive, active role in the production of behavior. The central pattern generator (CPG) that drives the consummatory feeding behaviors of Aplysia generates large, quasi-random variability in the parameters of the feeding motor programs from one cycle to the next; the variability then propagates through the firing patterns of the motor neurons to the contractions of the feeding muscles. We have proposed that, when the animal is faced with a new, imperfectly known feeding task in each cycle, the variability implements a trial-and-error search through the space of possible feeding movements. Although this strategy will not be successful in every cycle, over many cycles it may be the optimal strategy for feeding in an uncertain and changing environment. To play this role, however, the variability must actually appear in the feeding movements and, presumably, in the functional performance of the feeding behavior. Here we have tested this critical prediction. We have developed a technique to measure, in intact, freely feeding animals, the performance of Aplysia swallowing behavior, by continuously recording with a length transducer the movement of the seaweed strip being swallowed. Simultaneously, we have recorded with implanted electrodes activity at each of the internal levels, the CPG, motor neurons, and muscles, of the feeding neuromusculature. Statistical analysis of a large data set of these recordings suggests that functional performance is not determined strongly by one or a few parameters of the internal activity, but weakly by many. Most important, the internal variability does emerge in the behavior and its functional performance. Even when the animal is swallowing a long, perfectly regular seaweed strip, remarkably, the length swallowed from cycle to cycle is extremely variable, as variable as the parameters of the activity of the CPG, motor neurons, and muscles.
Neuromuscular Adaptation During Skill Acquisition on a Two Degree-of-Freedom Target-Acquisition Task: Isometric Torque Production
Authors: Shemmell Jonathan , Forner Matthew , Tresilian James R. , Riek Stephan , Barry Benjamin K. , Carson Richard G.
Published: June 2005

In this study we attempted to identify the principles that govern the changes in neural control that occur during repeated performance of a multiarticular coordination task. Eight participants produced isometric flexion/extension and pronation/supination torques at the radiohumeral joint, either in isolation (e.g., flexion) or in combination (e.g., flexion–supination), to acquire targets presented by a visual display. A cursor superimposed on the display provided feedback of the applied torques. During pre- and postpractice tests, the participants acquired targets in eight directions located either 3.6 cm (20% maximal voluntary contraction [MVC]) or 7.2 cm (40% MVC) from a neutral cursor position. On each of five consecutive days of practice the participants acquired targets located 5.4 cm (30% MVC) from the neutral position. EMG was recorded from eight muscles contributing to torque production about the radiohumeral joint during the pre- and posttests. Target-acquisition time decreased significantly with practice in most target directions and at both target torque levels. These performance improvements were primarily associated with increases in the peak rate of torque development after practice. At a muscular level, these changes were brought about by increases in the rates of recruitment of all agonist muscles. The spatiotemporal organization of muscle synergies was not significantly altered after practice. The observed adaptations appear to lead to performances that are generalizable to actions that require both greater and smaller joint torques than that practiced, and may be successfully recalled after a substantial period without practice. These results suggest that tasks in which performance is improved by increasing the rate of muscle activation, and thus the rate of joint torque development, may benefit in terms of the extent to which acquired levels of performance are maintained over time.
Chronometry of Visual Responses in Frontal Eye Field, Supplementary Eye Field, and Anterior Cingulate Cortex
Authors: Pouget Pierre , Emeric Erik E. , Stuphorn Veit , Reis Kate , Schall Jeffrey D.
Published: June 2005

The latency and variability of latency of single-unit responses to identical visual stimulation were measured in the frontal eye field (FEF), supplementary eye field (SEF), and anterior cingulate cortex (ACC) of macaque monkeys performing visually guided saccades. The mean visual response latency was significantly shorter in FEF (64 ms) than in SEF (81 ms) or ACC (100 ms), and latency values determined by four methods agreed. The latency variability of the visual response was respectively less in FEF (21 ms) than in SEF (37 ms) or ACC (41 ms). Latency, variability of latency, and magnitude of the visual responses were correlated within FEF and SEF but not ACC. These characteristics of the visual response are consistent with the degree of convergence of visual afferents to these areas and constrain hypotheses about visual processing in the frontal lobe.
Gene expression profiling of experimental traumatic spinal cord injury as a function of distance from impact site and injury severity
Authors: De Biase Andrea , Knoblach Susan M. , Di Giovanni Simone , Fan Chenguang , Molon Annamaria , Hoffman Eric P. , Faden Alan I.
Published: June 2005

Changes in gene expression contribute to pathophysiological alterations following spinal cord injury (SCI). We examined gene expression over time (4 h, 24 h, 7 days) at the impact site, as well as rostral and caudal regions, following mild, moderate, or severe contusion SCI in rats. High-density oligonucleotide microarrays were used that included ∼27,000 genes/ESTs (Affymetrix RG-U34; A, B and C arrays), together with multiple analyses (MAS 5.0, dChip). Alterations after mild injury were relatively rapid (4 and 24 h), whereas they were delayed and prolonged after severe injury (24 h and 7 days). The number and magnitude of gene expression changes were greatest at the injury site after moderate injury and increased in rostral and caudal regions as a function of injury severity. Sham surgery resulted in expression changes that were similar to mild injury, suggesting the importance of using time-linked surgical controls as well as naive animals for these kinds of studies. Expression of many genes and ESTs was altered; these were classified functionally based on ontology. Overall representation of these functional classes varied with distance from the site of injury and injury severity, as did the individual genes that contributed to each functional class. Different clustering approaches were used to identify changes in neuronal-specific genes and several transcription factors that have not previously been associated with SCI. This study represents the most comprehensive evaluation of gene expression changes after SCI to date. The results underscore the power of microarray approaches to reveal global genomic responses as well as changes in particular gene clusters and/or families that may be important in the secondary injury cascade.
Pathway analysis of coronary atherosclerosis
Authors: King Jennifer Y. , Ferrara Rossella , Tabibiazar Raymond , Spin Joshua M. , Chen Mary M. , Kuchinsky Allan , Vailaya Aditya , Kincaid Robert , Tsalenko Anya , Deng David Xing-Fei , Connolly Andrew , Zhang Peng , Yang Eugene , Watt Clifton , Yakhini Zohar , Ben-Dor Amir , Adler Annette , Bruhn Laurakay , Tsao Philip , Quertermous Thomas , Ashley Euan A.
Published: June 2005

Large-scale gene expression studies provide significant insight into genes differentially regulated in disease processes such as cancer. However, these investigations offer limited understanding of multisystem, multicellular diseases such as atherosclerosis. A systems biology approach that accounts for gene interactions, incorporates nontranscriptionally regulated genes, and integrates prior knowledge offers many advantages. We performed a comprehensive gene level assessment of coronary atherosclerosis using 51 coronary artery segments isolated from the explanted hearts of 22 cardiac transplant patients. After histological grading of vascular segments according to American Heart Association guidelines, isolated RNA was hybridized onto a customized 22-K oligonucleotide microarray, and significance analysis of microarrays and gene ontology analyses were performed to identify significant gene expression profiles. Our studies revealed that loss of differentiated smooth muscle cell gene expression is the primary expression signature of disease progression in atherosclerosis. Furthermore, we provide insight into the severe form of coronary artery disease associated with diabetes, reporting an overabundance of immune and inflammatory signals in diabetics. We present a novel approach to pathway development based on connectivity, determined by language parsing of the published literature, and ranking, determined by the significance of differentially regulated genes in the network. In doing this, we identify highly connected “nexus” genes that are attractive candidates for therapeutic targeting and followup studies. Our use of pathway techniques to study atherosclerosis as an integrated network of gene interactions expands on traditional microarray analysis methods and emphasizes the significant advantages of a systems-based approach to analyzing complex disease.
Proinflammatory Liver and Antiinflammatory Intestinal Mediators Involved in Portal Hypertensive Rats
Authors: Aller Maria Angeles , Vara Elena , Garcia Cruz , Palma Maria Dolores , Arias Jorge L. , Nava Maria Paz , Arias Jaime
Published: June 2005

Proinflammatory (TNF‐α, IL‐1β, and NO) and antiinflammatory (IL‐10, CO) levels were assayed in serum, liver,
and small bowel in order to verify a hypothetic inflammatory etiopathogeny of portal hypertension that could be the cause of its evolutive heterogeneity. Male Wistar rats were divided into one control group (n = 11) and one group with a triple stenosing ligation of the portal vein (n = 23) after 28 days of evolution. In one subgroup of portal hypertensive rats,
portal pressure, collateral venous circulation, mesenteric vasculopathy, and liver and spleen weights were determined. In the remaining rats with portal hypertension TNF‐α, IL‐1β, and IL‐10 were quantified in liver and ileum by enzyme‐linked immunosorbent assay. NO synthase activity was studied in liver and ileum. CO and NO were measured in portal and systemic blood by spectrophotometry and Griess reaction, respectively. Portal hypertensive rats with mayor spleen weight show hepatomegaly and mayor development of collateral circulation. Ileum release of IL‐10 (0.30 ± 0.12 versus 0.14 ± 0.02 pmol/mg protein; P < .01) is associated with a liver production of both proinflammatory mediators (TNF‐α: 2 ± 0.21 versus 1.32 ± 0.60 pmol/mg protein; P < .05, IL‐1β: 19.17 ± 2.87 versus 5.96 ± 1.84pmol/mg
protein; P = .005, and NO: 132.10 ± 34.72 versus 61.05 ± 8.30nmol/mL; P = .005) and an antiinflammatory mediator (CO: 6.49 ± 2.99 versus 3.03 ± 1.59pmol/mL; P = .005). In short‐term prehepatic portal hypertension a gut‐liver inflammatory loop, which could be fundamental in the regulation both of the portal pressure and of its complications,
could be proposed.
Regulatory Mechanisms for Neural Crest Formation
Authors: Sakai Daisuke , Wakamatsu Yoshio
Published: June 2005

In early vertebrate development, the neural crest is specified in the embryonic ectoderm at the boundary of the neural plate and the nonneural ectoderm. After the induction, the neural crest cells undergo epithelial-mesenchymal transition, delaminating from the epithelium, and migrate extensively in the embryonic environment to give rise to a wide variety of tissues and cell types. In this review, we try to summarize the recent progress in understanding the molecular nature of the inductive signals and transcription factors involved in neural crest formation and following steps of the neural crest development. We also point out the underlying problems that need to be solved to understand the process further.
Mesenchymal-to-Epithelial Transition during Somitic Segmentation: A Novel Approach to Studying the Roles of Rho Family GTPases in Morphogenesis
Authors: Takahashi Yoshiko , Sato Yuki , Suetsugu Rinako , Nakaya Yukiko
Published: June 2005

During early development in vertebrates, cells change their shapes dramatically both from epithelial to mesenchymal and also from mesenchymal to epithelial, enabling the body to form complex tissues and organs. Using somitogenesis as a novel model, Rho family GTPases have recently been shown to play essential and differential roles in individual cell behaviors in actual developing embryos. Levels of Cdc42 activity provide a binary switch wherein high Cdc42 levels allow the cells to remain mesenchymal, while low Cdc42 levels produce epithelialization. Rac1 activity needs to be precisely controlled for proper epithelialization through the bHLH transcription factor Paraxis. Somitogenesis is expected to serve as an excellent model with which one can understand how the functions of developmental genes are resolved into the morphogenetic behavior of individual cells.
Transforming Growth Factor-β-Induced Epithelial-Mesenchymal Transition in the Lens: A Model for Cataract Formation
Authors: de Iongh R.U. , Wederell E. , Lovicu F.J. , McAvoy J.W.
Published: June 2005

The vertebrate lens has a distinct polarity and structure that are regulated by growth factors resident in the ocular media. Fibroblast growth factors, in concert with other growth factors, are key regulators of lens fiber cell differentiation. While members of the transforming growth factor (TGFβ) superfamily have also been implicated to play a role in lens fiber differentiation, inappropriate TGFβ signaling in the anterior lens epithelial cells results in an epithelial-mesenchymal transition (EMT) that bears morphological and molecular resemblance to forms of human cataract, including anterior subcapsular (ASC) and posterior capsule opacification (PCO; also known as secondary cataract or after-cataract), which occurs after cataract surgery. Numerous in vitro and in vivo studies indicate that this TGFβ-induced EMT is part of a wound healing response in lens epithelial cells and is characterized by induced expression of numerous extracellular matrix proteins (laminin, collagens I, III, tenascin, fibronectin, proteoglycans), intermediate filaments (desmin, α-smooth muscle actin) and various integrins (α2, α5, α7B), as well as the loss of epithelial genes [Pax6, Cx43, CP49, α-crystallin, E-cadherin, zonula occludens-1 protein (ZO-1)]. The signaling pathways involved in initiating the EMT seem to primarily involve the Smad-dependent pathway, whereby TGFβ binding to specific high affinity cell surface receptors activates the receptor-Smad/Smad4 complex. Recent studies implicate other factors [such as fibroblast growth factor (FGFs), hepatocyte growth factor, integrins], present in the lens and ocular environment, in the pathogenesis of ASC and PCO. For example, FGF signaling can augment many of the effects of TGFβ, and integrin signaling, possibly via ILK, appears to mediate some of the morphological features of EMT initiated by TGFβ. Increasing attention is now being directed at the network of signaling pathways that effect the EMT in lens epithelial cells, with the aim of identifying potential therapeutic targets to inhibit cataract, particularly PCO, which remains a significant clinical problem in ophthalmology.
Invasion and Metastasis in Colorectal Cancer: Epithelial-Mesenchymal Transition, Mesenchymal-Epithelial Transition, Stem Cells and β-Catenin
Authors: Brabletz Thomas , Hlubek Falk , Spaderna Simone , Schmalhofer Otto , Hiendlmeyer Elke , Jung Andreas , Kirchner Thomas
Published: June 2005

Invasion by colorectal carcinomas is characterized by an epithelial-mesenchymal transition (EMT)-like dedifferentiation of the tumor cells. However, a redifferentiation towards an epithelial phenotype, resembling a mesenchymal-epithelial transition, is detectable in metastases. This indicates that malignant progression is based on dynamic processes, which cannot be explained solely by irreversible genetic alterations, but must be additionally regulated by the tumor environment. The main oncoprotein in colorectal cancer is the Wnt pathway effector β-catenin, which is overexpressed due to mutations in the APC tumor suppressor in most cases. EMT of the tumor cells is associated with a nuclear accumulation of the transcriptional activator β-catenin, which is reversed in metastases. Nuclear β-catenin is involved in two fundamental processes in embryonic development: EMT and stem cell formation. Accumulating data demonstrate that aberrant nuclear expression of β-catenin can also confer these two abilities to tumor cells, thereby driving malignant tumor progression.
Hyaluronan: A Critical Component of Epithelial-Mesenchymal and Epithelial-Carcinoma Transitions
Authors: Toole Bryan P. , Zoltan-Jones Alexandra , Misra Suniti , Ghatak Shibnath
Published: June 2005

Hyaluronan plays a central role in the transition of epithelia to mesenchyme in the embryo and in the acquisition of transformed properties in carcinoma cells. In some cases, hyaluronan is both essential and sufficient for induction of epithelial-mesenchymal transitions (EMTs). Underlying its role are the effects of hyaluronan on receptor kinase activities, cell survival pathways, and multidrug transporters. A more complete understanding of the mechanisms whereby hyaluronan exerts its influences on cell behavior will enhance our understanding of normal and pathological EMTs and may lead to improved therapies for cancer patients.
The Src-Induced Mesenchymal State in Late-Stage Colon Cancer Cells
Authors: Avizienyte Egle , Brunton Valerie G. , Fincham Valerie J. , Frame Margaret C.
Published: June 2005

One major function of elevated Src kinase in epithelial cancer cells is to drive adhesion changes that are associated with the mesenchymal transition and metastasis [Jones et al., Br J Cancer 2002;87:1128–1135]. Here we review recent work that describes Src-induced shape changes, and the mechanisms involved, in cells derived from a model of colon cancer metastasis. Src activity in these cells is associated with formation and dynamic regulation of integrin adhesions and disorganization of E-cadherin-dependent cell-cell contacts. Furthermore, Src-induced deregulation of E-cadherin requires integrin signalling [Avizienyte et al., Nat Cell Biol 2002;4:632–638], demonstrating a complex interdependence between integrin- and cadherin-associated adhesion changes induced by Src. The integrin-induced signals that co-operate with Src to cause deregulation of cadherin-dependent cell-cell contacts include activation of the MEK/ERK and MLCK/myosin activities. Inhibition of this pathway suppresses integrin complexes formed on fibronectin, while promoting E-cadherin redistribution to sites of cell-cell contacts [Avizienyte et al., Mol Biol Cell 2004;15:2794–2803]. Also, in embryonic fibroblasts that express N-cadherin (which is normally diffusely cytoplasmic as these cells maintain a fibroblastic morphology) suppressing integrin signalling and inhibiting the MEK/ERK/MLCK/myosin pathway relocalizes N-cadherin to cell-cell contacts. Our recent data therefore imply an important, and perhaps general, role for spatially controlled contractility in suppressing normal cadherin localization and inducing a mesenchymal-like phenotype.
Role of Glucose Side Chains with Serotype-Specific Polysaccharide in the Cariogenicity of Streptococcus mutans
Authors: Nakano K. , Nomura R. , Nakagawa I. , Hamada S. , Ooshima T.
Published: June 2005

Previously, we isolated and characterized a new Streptococcus mutans strain (serotype k) from human blood and oral cavity samples, and found that the serological properties of serotype k strains were similar to those of a gluA-inactivated mutant strain of MT8148 (MT8148GD). MT8148GD showed significantly lower sucrose-dependent adhesion to glass surfaces, sucrose-independent adhesion to saliva-coated hydroxyapatite, dextran-binding activity, and cell-associated glucosyltransferase (GTF) activity than the parent strain. Further, Western blot analysis revealed reduced GTFB and GTFC expression in serotype k strains as compared to MT8148, though the caries-inducing activities of MT8148GD and a serotype k oral isolate in rats were similar to that of MT8148. We conclude that a glucose side-chain defect in the serotype-specific polysaccharide of S. mutans may be associated with its cariogenicity, though to a lesser extent than its other major surface proteins.
Responder and Nonresponder Analysis for a Caries Prevention Program
Authors: Splieth Ch.H. , Steffen H. , Welk A. , Schwahn Ch.
Published: June 2005

To be able to generalize studies, it is important to know whether responders and nonresponders differ significantly. These data are usually not available. To assess whether responders and nonresponders differed significantly, 319 first and second graders in Greifswald, Germany took part in a compulsory dental school examination. Their parents completed a questionnaire on oral health topics and were asked to decide about their children’s participation in a school-based caries prevention program plus anonymous scientific evaluation. The 91 children who were not allowed to participate (nonresponders) were older (mean 8.5 years) than the 228 responders (mean 8.1 years; p < 0.001), mostly because of a few older children having repeated a grade. In an age-adjusted analysis, nonresponders exhibited in 21 of 30 indices of higher caries and plaque values, less preventive measures and a lower rate of participation. The difference in caries in the permanent dentition and fluorosis reached statistical significance. This study suggests that nonresponders to caries prevention programs might comply less with preventive measures and exhibit poorer oral health than responders: a result which has to be taken into account in research and prevention programs in the community.
Clinical Study on the Effect of Professional Cleaning of Occlusal Tooth Surfaces on Laser Fluorescence Measurements
Authors: Anttonen V. , Seppä L. , Hausen H.
Published: June 2005

Manufacturer’s advice is to professionally clean teeth before using a laser fluorescence (LF) device in order to avoid false-positive diagnoses. Professional cleaning is not included in routine dental check-ups in children in Finland because it is time-consuming. The aim of our present study was to evaluate the effect of professional cleaning of teeth on LF in children. A total of 642 occlusal surfaces in permanent molars and premolars in 9- to 16-year-olds (n = 46) were first examined visually. After that the first measurements with LF were made without cleaning the teeth. At the same appointment the second measurements were carried out after professional cleaning using a soft rubber cup and either polishing paste or plain water spray. The differences in LF of uncleaned and cleaned teeth were determined separately for teeth with a visual score of 0 (sound) and >0. In premolars cleaning had no significant effect on LF. In molars, the values increased when the teeth were cleaned, the difference of the measurements being statistically significant in molars with visual score >0 cleaned with plain water spray. For molars that were cleaned with paste, the differences were not statistically significant. Sealants did not modify the effect of cleaning. As a conclusion cleaning with a rotating instrument and water spray before LF measurements is recommended in teeth with visible plaque. Also in clean teeth, cleaning is advisable in cases where LF readings approach threshold level for operative intervention. The finding that uncleaned teeth gave lower values than cleaned teeth is opposite to what has been suggested.
Influence of Professional Cleaning and Drying of Occlusal Surfaces on Laser Fluorescence in vivo
Authors: Lussi A. , Longbottom C. , Gygax M. , Braig F.
Published: June 2005

Three dentists recorded laser fluorescence (LF) values on 117 teeth in 70 patients, in the sequence: (1) moist, uncleaned; (2) dried, uncleaned; (3) moist, cleaned; (4) dried, cleaned. LF values varied significantly with surface status (p < 0.01). The optimal cutoffs were up to 5 units lower on uncleaned, moist surfaces compared to the other states. Drying uncleaned surfaces significantly increased LF readings for dentinal caries (p < 0.01). It was concluded that occlusal surfaces should be clean and dry, for precise longitudinal monitoring of caries with LF as well as for detailed visual inspection, which should precede LF measurements.
Expression of the CD44 Receptor in the Blood Vessel System: An Experimental Study in Rat
Authors: Hellström Martin , Engström-Laurent Anna , Hellström Sten
Published: June 2005

The CD44 receptor is a transmembrane glycoprotein expressed on a variety of cells like endothelial, epithelial and smooth muscle cells. This molecule has many important functions, e.g. in cell-cell and cell-matrix interactions and signal transduction. The main ligand for CD44 is hyaluronan (HYA). HYA is a glycosaminoglycan with structural and cell biological properties. The localization of HYA in the vessel wall of arteries and veins in the healthy adult and newborn rat has been described earlier. In this study the occurrence of the CD44 receptor was investigated in the same vessels and compared to the localization of HYA. Both CD44 and its ligand showed an increased expression in the vessel wall of newborn rats compared to that of adult rats. Although HYA is abundant in the adventitia of adult rats, virtually no expression of CD44 was observed. Our results indicate that the CD44 receptor expression is increased during the stage of maturation of the vessel tree whereas the CD44 receptor is less needed by HYA in the healthy vessel wall.
Concerted Upregulation of CLP36 and Smooth Muscle Actin Protein Expression in Human Endometrium during Decidualization
Authors: Miehe Ulrich , Neumaier-Wagner Peruka , Kadyrov Mamed , Goyal Pankaj , Alfer Joachim , Rath Werner , Huppertz Berthold
Published: June 2005

The human endometrium prepares for implantation of the blastocyst by reorganization of its whole cellular network. Endometrial stroma cells change their phenotype starting around the 23rd day of the menstrual cycle. These predecidual stroma cells first appear next to spiral arteries, and after implantation these cells further differentiate into decidual stroma cells. The phenotypical changes in these cells during decidualization are characterized by distinct changes in the actin filaments and filament-related proteins such as α-actinin. The carboxy-terminal LIM domain protein with a molecular weight of 36 kDa (CLP36) is a cytoskeletal component that has been shown to associate with contractile actin filaments and to bind to α-actinin supporting a role for CLP36 in cytoskeletal reorganization and signal transduction by binding to signaling proteins. The expression patterns of CLP36, α-actinin and actin were studied in endometrial stroma cells from different stages of the menstrual cycle and in decidual stroma cells from the 6th week of gestation until the end of pregnancy. During the menstrual cycle, CLP36 is only expressed in the luminal and glandular epithelium but not in endometrial stroma cells. During decidualization and throughout pregnancy, a parallel upregulation of CLP36 and smooth muscle actin, an early marker of decidualization in the baboon, was observed in endometrial decidual cells. Since both proteins maintain a high expression level throughout pregnancy, a role of both proteins is suggested in the stabilization of the cytoskeleton of these cells that come into close contact with invading trophoblast cells.
Novel Metal Clusters Isolated from Blood Are Lethal to Cancer Cells
Authors: Samoylov Alexander M. , Samoylova Tatiana I. , Pustovyy Oleg M. , Samoylov Alexei A. , Toivio-Kinnucan Maria A. , Morrison Nancy E. , Globa Ludmila P. , Gale William F. , Vodyanoy Vitaly
Published: June 2005

Unfolding and subsequent aggregation of proteins is a common phenomenon that is linked to many human disorders. Misfolded hemoglobin is generally manifested in various autoimmune, infectious and inherited diseases. We isolated micrometer and submicrometer particles, termed proteons, from human and animal blood. Proteons lack nucleic acids but contain two major polypeptide populations with homology to the hemoglobin α-chain. Proteons form by reversible seeded aggregation of proteins around proteon nucleating centers (PNCs). PNCs are comprised of 1- to 2-nm metallic nanoclusters containing 40–300 atoms. Each milliliter of human blood contained approximately 7 × 1013 PNCs and approximately 3 × 108 proteons. Exposure of isolated blood plasma to elevated temperatures increased the number of proteons. When an aliquot of this heated plasma was introduced into untreated plasma that was subsequently heated, the number of proteons further increased, reaching a maximum after a total of three such iterations. Small concentrations of PNCs were lethal to cultured cancer cells, whereas noncancerous cells were much less affected.
Hamstring Muscles: Architecture and Innervation
Authors: Woodley Stephanie J. , Mercer Susan R.
Published: June 2005

Knowledge of the anatomical organization of the hamstring muscles is necessary to understand their functions, and to assist in the development of accurate clinical and biomechanical models. The hamstring muscles were examined by dissection in six embalmed human lower limbs with the purpose of clarifying their gross morphology. In addition to obtaining evidence for or against anatomical partitioning (as based on muscle architecture and pattern of innervation), data pertaining to architectural parameters such as fascicular length, volume, physiological cross-sectional area, and tendon length were collected. For each muscle, relatively consistent patterns of innervation were identified between specimens, and each was unique with respect to anatomical organization. On the basis of muscle architecture, three regions were identified within semimembranosus. However, this was not completely congruent with the pattern of innervation, as a primary nerve branch supplied only two regions, with the third region receiving a secondary branch. Semitendinosus comprised two distinct partitions arranged in series that were divided by a tendinous inscription. A singular muscle nerve or a primary nerve branch innervated each partition. In the biceps femoris long head the two regions were supplied via a primary nerve branch which divided into two primary branches or split into a series of branches. Being the only muscle to cross a single joint, biceps femoris short head consisted of two distinct regions demarcated by fiber direction, with each innervated by a separate muscle nerve. Architecturally, each muscle differed with respect to parameters such as physiological cross-sectional area, fascicular length and volume, but generally all partitions within an individual muscle were similar in fascicular length. The long proximal and distal tendons of these muscles extended into the muscle bellies thereby forming elongated musculotendinous junctions.
Mitochondria in Amyotrophic Lateral Sclerosis: A Trigger and a Target
Authors: Dupuis Luc , Gonzalez de Aguilar Jose-Luis , Oudart Hugues , de Tapia Marc , Barbeito Luis , Loeffler Jean-Philippe
Published: June 2005

Strong evidence shows that mitochondrial dysfunction is involved in amyotrophic lateral sclerosis (ALS), but despite the fact that mitochondria play a central role in excitotoxicity, oxidative stress and apoptosis, the intimate underlying mechanism linking mitochondrial defects to motor neuron degeneration in ALS still remains elusive. Morphological and functional abnormalities occur in mitochondria in ALS patients and related animal models, although their exact nature and extent are controversial. Recent studies postulate that the mislocalization in mitochondria of mutant forms of copper-zinc superoxide dismutase (SOD1), the only well-documented cause of familial ALS, may account for the toxic gain of function of the enzyme, and hence induce motor neuron death. On the other hand, mitochondrial dysfunction in ALS does not seem to be restricted only to motor neurons as it is also present in other tissues, particularly the skeletal muscle. The presence of this ‘systemic’ defect in energy metabolism associated with the disease is supported in skeletal muscle tissue by impaired mitochondrial respiration and overexpression of uncoupling protein 3. In addition, the lifespan of transgenic mutant SOD1 mice is increased by a highly energetic diet compensating both the metabolic defect and the motorneuronal function. In this review, we will focus on the mitochondrial dysfunction linked to ALS and the cause-and-effect relationships between mitochondria and the pathological mechanisms thought to be involved in the disease.
Influence of Different Promoters on the Expression Pattern of Mutated Human α-Synuclein in Transgenic Mice
Authors: Maskri Lyutha , Zhu XinRan , Fritzen Sabrina , Kühn Kati , Ullmer Christoph , Engels Peter , Andriske Michael , Stichel Christine C. , Lübbert Hermann
Published: June 2005

Two missense mutations (A53T and A30P) in the gene encoding the presynaptic protein α-synuclein (asyn) are associated with rare, dominantly inherited forms of Parkinson’s disease (PD) and its accumulation in Lewy bodies and Lewy neurites. As an initial step in investigating the role of asyn in the pathogenesis of PD, we have generated C57BL/6 transgenic mice overexpressing the doubly mutated human asyn under the control of three different promoters; the chicken β-actin (chβactin), the mouse tyrosine hydroxylase 9.6 kb (msTH) and the mouse prion protein (msprp). In this study we compared the regional and cellular expression pattern of the transgenic protein in the brain and peripheral organs of various transgenic mouse lines. Western blot analysis and immunohistochemistry consistently showed that all three promoters successfully drive the expression of the transgene. The msprp promoter was found to give the highest level of transgene expression. All promoters directed the expression into the brain and specific neuron types. However, the promoters differed with respect to (i) the expression pattern in peripheral organs, (ii) the number and (iii) the regional distribution of expressing cells in the brain. Furthermore, remarkable line-to-line variation of expression patterns was observed in mouse lines carrying the same construct. Future studies will analyze how the variations in transgene expression affect the pathogenesis in the animals.
Unchanged Scrapie Pathology in Brain Tissue of Tyrosine Kinase Fyn-Deficient Mice
Authors: Schwarz Anja , Burwinkel Michael , Riemer Constanze , Schultz Julia , Baier Michael
Published: June 2005

Fyn is a 59-kDa member of the Src family of tyrosine kinases synthesized on cytosolic polysomes and then targeted to the plasma membrane where it clusters in caveolae-like membrane microdomains. The cellular isoform of the prion protein (PrP) has also been identified to be a caveolar constituent and to participate in signal transduction events concerning cell survival and differentiation via recruitment of Fyn. We studied the scrapie infection of mice deficient for Fyn (Fyn–/–) to clarify the role of Fyn in an in vivo model of transmissible spongiforme encephalopathies. Fyn–/– mice died on average 9 days earlier than wild-type control mice, but no differences were seen regarding activation of astrocytes, vacuolization of the neuropil, and accumulation of misfolded prion protein. The experimental model suggests that a deficiency for Fyn is detrimental in prion diseases, although it has no major effect on the clinical course of an experimental prion infection of the CNS.
The Role of Cranial Expansion for Craniocephalic Disproportion
Authors: Gough Jenny , Walker David G. , Theile Richard , Tomlinson Francis H.
Published: June 2005

The appropriate treatment for craniocephalic disproportion, such as caused by slit ventricle syndrome, is uncertain. We have reviewed the treatment and outcomes of 4 children who underwent cranial expansion over a period of 5 years. The ages at cranial expansion were 16 months, 3 years 6 months and 2 at 6 years. Two children had slit ventricle syndrome and were treated with bilateral parietal expansions. Two children had non-syndromic craniosynostosis, one of these having vitamin D-resistant rickets. The latter 2 were treated with posterior cranial vault expansion, and one also had a craniocervical junction decompression performed. Post-operatively, symptoms of raised intracranial pressure resolved in all cases, and there was radiological evidence of re-establishment of normal CSF pathways. Although a rare condition, cranial expansion operations can be successful in appropriately selected cases of craniocephalic disproportion.
Surgical Treatment of Epilepsy in Children Caused by Focal Cortical Dysplasia
Authors: Hudgins Roger J. , Flamini J. Robert , Palasis Susan , Cheng Raymond , Burns Thomas G. , Gilreath C. Lynn
Published: June 2005

Focal cortical dysplasia (FCD) is a congenital disorder of neuronal migration that is increasingly recognized as a common cause of seizures in children, occurring in 20–30% of all surgically treated cases of epilepsy in the pediatric population. Advances in neuroimaging have contributed to recognition of FCD. We report 15 children (9 female, 6 male) with FCD and surgically treated intractable epilepsy. In 9 cases, a surgical strategy of anatomic (frameless stereotactic) grid placement and physiologic (electrocorticography) resection was employed. Postoperative MRI scans were obtained, the pathologic specimen was graded according to the Brannstrom system, and seizure outcome was defined using the Engel classification. There were no deaths and no permanent morbidity. After, on average, 4 years since treatment, 10 children are seizure free, 2 are 2A, 2 are 2B and 1 is 3A. Predictors of good outcome are an MRI-defined lesion and increased cortical disorganization (higher Brannstrom grade). Subtotal resection did not preclude a seizure-free outcome.
Abdominal Pseudocyst: Predisposing Factors and Treatment Algorithm
Authors: Mobley 3rd Lloyd W. , Doran Stephen E. , Hellbusch Leslie C.
Published: June 2005

Abdominal pseudocyst (APC) is an uncommon complication of ventriculoperitoneal shunts. Various predisposing factors have been attributed to it, including the presence of infection and multiple shunt revisions. We reviewed the records of shunt revisions performed over a 20-year period. During that time, 64 cases of APC were found in 36 patients. The records were then reviewed for the presence of infection, history of necrotizing enterocolitis, prior abdominal surgery, and treatment performed. Of the cases of APC, 46 were primary and 18 were recurrent. A history of prior abdominal surgery other than shunt revision was found in 47% of patients and a history of necrotizing enterocolitis was found in 19% of patients. The average number of prior shunt revisions was 4.1 per patient. Shunt infection as defined by positive cultures of either cerebrospinal fluid or abdominal fluid was present in only 23% of cases of APC. A history of prior shunt infection was present in 30% of patients. Infection was treated by shunt removal, external ventricular drainage, and appropriate antibiotics. After the infection was cleared or if no infection was present, treatment consisted of: (1) repositioning the distal catheter into the peritoneum, (2) repositioning the distal catheter into the pleural space, the atrium, or the gallbladder, (3) exploratory laparotomy with lysis of adhesions and repositioning the peritoneal catheter, (4) APC aspiration only, or (5) shunt removal or disconnection. Because of the complexity of APC management, we analyzed the outcomes of our cases and outlined an algorithm to simplify this process.
Spinal Lipomas in Children – Surgical Management and Long-Term Follow-Up
Authors: Morimoto Kazuyoshi , Takemoto Osamu , Wakayama Akatsuki
Published: June 2005

Since its introduction, MR imaging has been easy to perform on all children with lumbosacral cutaneous stigmata, and has enabled the phenomenal refinement of spinal pathology. We investigated the overall outcomes of children with spinal lipomas at the Osaka Medical Center and Research Institute for Maternal and Child Health in Osaka, Japan. Between 1991 and 2003, 76 children with a tethered cord underwent a total of 90 surgical procedures at our institutes. Of this cohort, 67 cases had spinal lipomas. The mean age of patients at first operation for asymptomatic lipoma was 22.4 months (range: 1 month to 16 years, trim mean: 10.1 months, mode: 5 months), except 4 cases. The mean total follow-up for the cohort since the first surgical procedure was 7.2 years (trim mean: 7.9 years). Since the introduction of MR imaging, the reoperation rate for symptoms or signs in our series was 16.4% (11 cases). Regarding the 13 subsequent reoperations (2 patients had 2 operations), 3 patients were reoperated on due to multiplication of the lipomas after untethering, 3 due to urologic symptoms and 5 due to orthopedic signs. There were 2 cases who also had to undergo reoperation early due to CSF leakage. Filum and conus lipomas have similar tethering pathologies, but differ in the outcome following surgery. Filum lipomas are benign, and therefore surgery is safe and effective. Conus lipomas are more difficult to manage.
Circumferential Cervical Spine Surgery in an 18-Month-Old Female with Traumatic Disruption of the Odontoid and C3 Vertebrae
Authors: Dickerman Rob D. , Morgan Jonathan T. , Mittler Mark
Published: June 2005

Study Design: A case study of an 18-month-old female with craniovertebral instability and spinal cord compression requiring circumferential stabilization. A review of surgical techniques in upper cervical spine and craniovertebral stabilization for young children is provided. Objectives: To describe an interesting surgical approach in a young pediatric patient requiring circumferential stability at the craniovertebral junction. Background Data: Craniovertebral instability is problematic in the young pediatric population due to the inability to secure hardware for stabilization. We present an interesting case of spinal cord compression with craniovertebral instability in an 18-month-old female requiring circumferential cervical spine and craniovertebral stabilization. Methods: The patient presented with acute onset quadriparesis after a fall. Radiographs demonstrated C2–C3 disruption with canal compromise. Magnetic resonance imaging revealed signal changes of the spinal cord at C2–C3. Neurological examination revealed normal muscle volume with strength 1/5 in the upper extremities and 0/5 in the lower extremities. Respirations were normal with normal diaphragmatic function. Cranial nerves were intact. Results: Halo-traction attempted at 0.453 kg induced occipital-atlantal dislocation. The patient underwent anterior corpectomy of C3 and the base of C2 with autologous rib grafts placed from C2 to C4 and macropore as an anterior plating system. Posteriorly the patient had occiput–C3 fusion with a titanium rod and autologous rib grafts bilaterally. Postoperatively the patient regained normal neurological function with circumferential fusion after 4 months in a halo vest. Conclusions: This case demonstrates the ability to achieve circumferential stabilization in the young pediatric patient. Injuries at the odontoid synchondrosis can be difficult to treat and are only complicated by having to achieve a posterior fusion at the craniovertebral junction. We present a successful case of circumferential fusion and offer a surgical technique to achieve spinal cord decompression and fusion of the upper cervical spine and craniovertebral junction in the young pediatric population..