bluuebunny/crossref_metadata_2025 huggingface dataset:
Perirhinal and parahippocampal cortices of the macaque monkey: Intrinsic projections and interconnections
Authors: Lavenex Pierre , Suzuki Wendy A. , Amaral David G.
Published: March 2004

We investigated the topographic and laminar organization of the intrinsic projections and interconnections of the macaque monkey perirhinal and parahippocampal cortices. Discrete anterograde tracer injections placed at various rostrocaudal and mediolateral levels in these cortices revealed extensive associational connections both within and between the perirhinal and parahippocampal cortices. Areas 35, 36rm, 36rl, 36cm, and 36cl are highly interconnected, whereas area 36d (encompassing the dorsal portion of the medial temporal pole) shares only modest connections with the rest of the perirhinal cortex. Areas TH, TFm, and TFl of the parahippocampal cortex also share an extensive network of associational connections that tend to be heaviest within a given subdivision. Area 36c of the perirhinal cortex is the main interface between the perirhinal and parahippocampal cortices. Its heaviest connections are with area 36r and the anterior aspect of area TF. The laminar organization of all these connections is typical of associational projections. Anterograde tracer experiments revealed that these projections are distributed through both deep and superficial layers, although heavier projections are directed toward the superficial layers. Results of retrograde tracer experiments suggested that the projections from caudal areas (36c or TF) to area 36r are of the feedforward type, whereas the projections from areas 36r and 36c to area TF are of the feedback type. These findings suggest that the perirhinal cortex is at a higher level than the parahippocampal cortex in the hierarchy of associational cortices. We discuss the functional implications of the organization of these extensive networks of intrinsic, associational projections. J. Comp. Neurol. 472:371–394, 2004. © 2004 Wiley‐Liss, Inc.
Grids of agents for computer and telecommunication network management
Authors: Assunção M. D. , Koch F. L. , Westphall C. B.
Published: March 2004

The centralized system approach for computer and telecommunication network management has been presenting scalability problems along with the growth in the amount and diversity of managed equipment. Moreover, the increase in complexity of the services being offered through the networks also contributes to adding extra workload to the management station. The amount of data that must be handled and processed by only one administration point could lead to a situation where there is not enough processing and storage power to carry out an efficient job. In this work we present an alternative approach by creating a highly distributed computing environment through the use of Grids of autonomous agents to analyze large amounts of data, which reduce the processing costs by optimizing the load distribution and resource utilization. Copyright © 2004 John Wiley & Sons, Ltd.
Applying the reflective middleware approach in Grid computing
Authors: Coulson Geoff , Blair Gordon , Parlavantzas Nikos , Yeung Wai Kit , Cai Wei
Published: March 2004

Significant progress has been made in the design and development of object‐based distributed systems and, more recently, in component‐based reflective middleware platforms—i.e. middleware platforms that, through reflection, can be flexibly configured, and runtime adapted/reconfigured—especially in terms of non‐functional properties like quality of service (QoS). In this paper we consider how ideas and principles from such platforms can usefully be applied in a Grid context, specifically, an Open Grid Services Architecture (OGSA) context. To this end, we identify weaknesses in OGSA in the areas of generic service provision, scalability/performance engineering, and, especially, lack of support for QoS specification and realization, and suggest how these can be alleviated. We believe that such areas will become increasingly important as sophisticated e‐Science applications start to exploit the potential of OGSA's service‐based architecture. We also report on our current research on developing a binding‐type framework, a resource management framework, and a set of performance optimizations for an ongoing OGSA implementation we are working on. Copyright © 2004 John Wiley & Sons, Ltd.
A resource management framework for interactive Grids
Authors: Kumar Raj , Talwar Vanish , Basu Sujoy
Published: March 2004

Traditional use of Grid computing systems has been for batch jobs in the scientific and academic computing. We envision the next generation Grid computing systems to support graphical interactive sessions. In this paper, we propose a resource management framework for supporting graphical interactive sessions in a Grid computing system. We describe the high‐level architectural resource management framework distributed among the submission node, central scheduler node, and the execution node. We then describe in detail the resource management framework on the execution node. The description of the resource management framework on the scheduler node is kept at a high level in this paper. The framework on execution nodes consists of Resource Management Agents, an Admission Control system and Application Predictor system. The agents on the execution node are Startup Agents, Sensor Agents, Monitoring Agents, Aggregator Agents, Enforcement Agents and Registration Agents. The Session Admission Control system is responsible for determining if a new application session can be admitted to the execution node. An Application Predictor system is responsible for predicting the resource utilization behavior of applications based on data obtained from the Resource Management Agents. The proposed framework allows for implementation of a scalable and extensible middleware for interactive Grid resource management. It supports fine‐grained performance guarantees specified in service level agreements and brings forth some important and novel contributions to enable graphical interactive sessions on Grids. Copyright © 2004 John Wiley & Sons, Ltd.
GridSphere: a portal framework for building collaborations
Authors: Novotny Jason , Russell Michael , Wehrens Oliver
Published: March 2004

Grid‐enabled portals are becoming increasingly popular as a platform for providing access to Grid services and resources. Unfortunately, much of the work done in portal development has led to vertically layered solutions that work for a particular project but are difficult to extend or reuse for other projects. The GridSphere portal framework seeks to address these limitations by providing a framework that will offer external developers a model for easily adding new functionality and hence increasing community collaboration. The GridLab portal will serve as an initial prototype to showcase the GridSphere framework and provide access to services being developed within the GridLab project. Copyright © 2004 John Wiley & Sons, Ltd.
Activation of nestin‐positive duct stem (NPDS) cells in pancreas upon neogenic motivation and possible cytodifferentiation into insulin‐secreting cells from NPDS cells
Authors: Kim So‐Yoon , Lee Seung‐Hee , Kim Byeong‐Moo , Kim Eun‐Ho , Min Bon‐Hong , Bendayan M. , Park In‐Sun
Published: March 2004

Stem cells in adult pancreas and their specific marker are poorly characterized. We hypothesized that pancreatic stem cells could evolve from the duct system in response to neogenic stimulation and may transiently express nestin during tissue regeneration. After partial pancreatectomy (Px), we found extensive formation of ductules consisting of nestin‐positive epithelial cells with higher replicating ability in the neogenic foci, particularly at day 3 after Px. Nestin was highly expressed in the earlier stages of ductule morphogenesis and then regressed as the cells evolved toward differentiated pancreatic cell types. The neogenic ductules were isolated for the culture of nestin‐positive duct stem cells. These nestin‐positive duct cells were numerous and displayed extensive self‐replication in the duct cell explants after 2–3 days of culture, thus depicted as nestin‐positive duct stem (NPDS) cells. As seen in the tissue of neogenic foci, NPDS cells were negative for cytokeratin‐20 and vimentin, the marker for duct epithelial and mesenchymal cells, respectively. Endocrine cells, mostly insulin cells, were present in the explants at day 2 as single cells or as small clusters adjacent to the NPDS cells, and formed islet‐like masses at day 3 of culture, suggesting islet cell differentiation from NPDS cells. In addition, insulin secretion from these beta cells responded to glucose stimulation. We found transient up‐regulation of PDX‐1 expression by reverse transcriptase‐polymerase chain reaction at day 3 after Px in pancreatic tissue. Higher expression of PDX‐1 was seen in the culture of neogenic ductules than that of ducts isolated from the sham‐operated pancreas. In particular, a subpopulation of nestin‐positive cells in the duct cell explants formed from the neogenic ductules expressed PDX‐1 in their nuclei. Taken together, this information suggests that NPDS cells could be generated from adult pancreas by neogenic motivations and they may differentiate into insulin‐secreting cells. Developmental Dynamics 230:1–11, 2004. © 2004 Wiley‐Liss, Inc.
VEGF coordinates interaction of pericytes and endothelial cells during vasculogenesis and experimental angiogenesis
Authors: Hagedorn Martin , Balke Maurice , Schmidt Annette , Bloch Wilhelm , Kurz Haymo , Javerzat Sophie , Rousseau Benoît , Wilting Joerg , Bikfalvi Andreas
Published: March 2004

Biological activities of vascular endothelial growth factor (VEGF) have been studied extensively in endothelial cells (ECs), but few data are available regarding its effects on pericytes. In murine embryoid body cultures, VEGF‐induced expression of desmin and α‐smooth muscle actin (α‐SMA) in CD‐31+ cells. The number of CD‐31+/desmin+ vascular chords increased with VEGF treatment time and peaked during a differentiation window between 6 and 9 days after plating. In vivo, VEGF‐induced elongation and migration of desmin‐positive pericytes and coverage of angiogenic capillaries, as revealed by analysis of Sambucus nigra lectin‐stained vascular beds of the chick chorioallantoic membrane. VEGF also caused significant decrease of intercapillary spaces, an indicator for intussusceptive vascular growth. These VEGF‐mediated effects point at a more intricate interaction between ECs and pericytes cells than previously demonstrated and suggest that pericytes may be derived from EC progenitors in vitro and not only stabilize capillaries but also participate in vascular remodeling in vivo. Developmental Dynamics 230:23–33, 2004. © 2004 Wiley‐Liss, Inc.
Formation and remodeling of the coronary vascular bed in the embryonic avian heart
Authors: Kattan Javier , Dettman Robert W. , Bristow James
Published: March 2004

To study the formation of the coronary vessels in the developing avian heart, we stained developmentally staged quail hearts with the endothelial specific antibody QH‐1. QH‐1 reacted with individual cells in the proepicardial organ in Hamburger and Hamilton stage (HH) 17 embryos only after it had contacted the heart. In HH18–26 hearts, individual QH‐1+ cells accumulated over the surface of the atria and ventricles. The first endothelial vessels appeared in the dorsal atrioventricular groove in HH23 hearts. CD45+ hematopoietic precursors accumulated on the heart surface, demonstrating the close temporal relationship of hematopoiesis with vasculogenesis during heart development. However, CD45 expression preceded association of these cells with the vasculature, suggesting hematopoietic commitment precedes formation of blood islands in the coronary vasculature. Endothelial tubules first appeared on the dorsal and then the ventral aspects of the heart, coalescing into large sinusoids. These sinusoids remodeled into compact muscularized vessels by HH35. Smooth muscle cell markers were first expressed at HH27 and only in association with developing vasculature. We did not observe markers of smooth muscle differentiation in the proepicardium, but it remains uncertain whether cells in the proepicardium are committed to this cell fate. Our data support a strictly vasculogenic mechanism for the formation of the coronary vessels and blood islands. Developmental Dynamics 230:34–43, 2004. © 2004 Wiley‐Liss, Inc.
Regulatory analysis of the mouseFgf3gene: Control of embryonic expression patterns and dependence upon sonic hedgehog (Shh) signalling
Authors: Powles Nicola , Marshall Heather , Economou Androulla , Chiang Chin , Murakami Akira , Dickson Clive , Krumlauf Robb , Maconochie Mark
Published: March 2004

Fgf3displays a dynamic and complex expression pattern during mouse embryogenesis. To address the molecular mechanisms underlyingFgf3expression, we used a transgenic approach to assay genomic regions from the mouseFgf3gene for regulatory activity. We identified an enhancer that mediates major components of embryonic expression, governing expression in the midbrain, hindbrain, surface ectoderm, dorsal roots and dorsal root ganglia (DRG), proximal sensory ganglia, and the developing central nervous system (CNS). Deletional analysis of the enhancer further delimited this regulatory activity to a 5.7‐kb fragment. We have also revealed sonic hedgehog (Shh) ‐dependent and Shh‐independent aspects ofFgf3expression through breeding theFgf3reporter transgene intoShhmutants. In the absence of Shh signalling,Fgf3reporter expression is lost in the ventral CNS, DRG, and superior cervical nerves, whereas activation of reporter expression in cranial ganglion cells is Shh independent. Moreover, detailed re‐examination of theShhphenotype revealed that Shh signalling is required for the correct development/maturation of the DRG. Developmental Dynamics 230:44–56, 2004. © 2004 Wiley‐Liss, Inc.
Use of fluorescent dextran conjugates as a long‐term marker of osteogenic neural crest in frogs
Authors: Gross Joshua B. , Hanken James
Published: March 2004

The neural crest is a population of multipotent stem cells unique to vertebrates. In the head, cranial neural crest (CNC) cells make an assortment of differentiated cell types and tissues, including neurons, melanocytes, cartilage, and bone. The earliest understanding of the developmental potentiality of CNC cells came from classic studies using amphibian embryos. Fate maps generated from these studies have been largely validated in recent years. However, a fate map for the most late‐developing structures in amphibians, and especially anurans (frogs), has never been produced. One such tissue type, skull bone, has been among the most difficult tissues to study due to the long time required for its development during anuran metamorphosis, which in some species may not occur until several months, or even years, after hatching. We report a relatively simple technique for studying this elusive population of neural crest‐derived osteogenic (bone‐forming) cells in Xenopus laevis by using fluorescently labeled dextran conjugates. Developmental Dynamics 230:100–106, 2004. © 2004 Wiley‐Liss, Inc.
A time‐accurate pseudo‐compressibility approach based on an unstructured hybrid finite volume technique applied to unsteady turbulent premixed flame propagation
Authors: Dourado Wladimyr M. C. , Bruel Pascal , Azevedo João L. F.
Published: March 2004

A preconditioning approach based on the artificial compressibility formulation is extended to solve the governing equations for unsteady turbulent reactive flows with heat release, at low Mach numbers, on an unstructured hybrid grid context. Premixed reactants are considered and a flamelet approach for combustion modelling is adopted using a continuous quenched mean reaction rate. An overlapped cell‐vertex finite volume method is adopted as a discretisation scheme. Artificial dissipation terms for hybrid grids are explicitly added to ensure a stable, discretised set of equations. A second‐order, explicit, hybrid Runge–Kutta scheme is applied for the time marching in pseudo‐time. A time derivative of the dependent variable is added to recover the time accuracy of the preconditioned set of equations. This derivative is discretised by an implicit, second‐order scheme. The resulting scheme is applied to the calculation of an infinite planar (one‐dimensional) turbulent premixed flame propagating freely in reactants whose turbulence is supposed to be frozen, homogeneous and isotropic. The accuracy of the results obtained with the proposed method proves to be excellent when compared to the data available in the literature. Copyright © 2004 John Wiley & Sons, Ltd.
Three‐dimensional incompressible flow calculations using the characteristic based split (CBS) scheme
Authors: Nithiarasu P. , Mathur J. S. , Weatherill N. P. , Morgan K.
Published: March 2004

In this paper, the characteristic based split scheme is employed for the solution of three‐dimensional incompressible viscous flow problems on unstructured meshes. Many algorithm related issues are discussed. Fully explicit and semiimplicit forms of the scheme are explained and employed in the calculation of both isothermal and nonisothermal incompressible flows simulation. The extension of the scheme to porous medium flows is also demonstrated with relevant examples. Copyright © 2004 John Wiley & Sons, Ltd.
Simulation of interface and free surface flows in a viscous fluid using adapting quadtree grids
Authors: Greaves Deborah
Published: March 2004

A new adaptive quadtree method for simulating laminar viscous fluid problems with free surfaces and interfaces is presented in this paper. The Navier–Stokes equations are solved with a SIMPLE‐type scheme coupled with the Compressive Interface Capturing Scheme for Arbitrary Meshes (CICSAM) (Numerical prediction of two fluid systems with sharp interfaces, Ph.D. Thesis, Imperial College of Science, Technology and Medicine, London, 1997) volume of fluid (VoF) method and PLIC reconstruction of the volume fraction field during refinement and derefinement processes. The method is demonstrated for interface advection cases in translating and shearing flow fields and found to provide high interface resolution at low computational cost. The new method is also applied to simulation of the collapse of a water column and the results are in excellent agreement with other published data. The quadtree grids adapt to follow the movement of the free surface, whilst maintaining a band of the smallest cells surrounding the surface. The calculation is made on uniform and adapting quadtree grids and the accuracy of the quadtree calculation is shown to be the same as that made on the equivalent uniform grid. Copyright © 2004 John Wiley & Sons, Ltd.
High resolution Godunov‐type schemes with small stencils
Authors: Guinot Vincent
Published: March 2004

Higher‐order Godunov‐type schemes have to cope with the following two problems: (i) the increase in the size of the stencil that make the scheme computationally expensive, and (ii) the monotony‐preserving treatments (limiters) that must be implemented to avoid oscillations, leading to strong damping of the solution, in particular linear waves (e.g. acoustic waves). When too compressive, limiting procedures may also trigger the instability of oscillatory numerical solutions (e.g. in advection–dispersion phenomena) via the artificial amplification of the shorter modes. The present paper proposes a new approach to carry out the reconstruction. In this approach, the values of the flow variable at the edges of the computational cells are obtained directly from the reconstruction within these cells. This method is applied to the MUSCL and DPM schemes for the solution of the linear advection equation. The modified DPM scheme can capture contact discontinuities within one computational cell, even after millions of time steps at Courant numbers ranging from 1 to values as low as 10‐4. Linear waves are subject to negligible damping. Application of the method to the DPM for one‐dimensional advection–dispersion problems shows that the numerical instability of oscillatory solutions caused by the over compressive, original DPM limiter is eliminated. One‐ and two‐dimensional shallow water simulations show an improvement over classical methods, in particular for two‐dimensional problems with strongly distorted meshes. The quality of the computational solution in the two‐dimensional case remains acceptable even for mesh aspect ratios Δx/Δy as large as 10. The method can be extend to the discretization of higher‐order PDEs, allowing third‐order space derivatives to be discretized using only two cells in space. Copyright © 2004 John Wiley & Sons, Ltd.
Adaptive strategy of the supersonic turbulent flow over a backward‐facing step
Authors: Yang Shih‐Ying
Published: March 2004

An adaptive strategy incorporating mesh remeshing and refining is developed to study the supersonic turbulent flow over a backward‐facing step on a mixed quadrilateral–triangular mesh. In the Cartesian co‐ordinate system, the unsteady Favre‐averaged Navier–Stokes equations with a low‐Reynolds‐number k–εturbulence model are solved using a locally implicit scheme with an anisotropic dissipation model. In the present adaptive strategy, two error indicators for both mesh remeshing and refining, respectively, are presented. The remeshing error indicator incorporates unified magnitude of substantial derivative of pressure and that of vorticity magnitude, whereas the refining error indicator incorporates unified magnitude of substantial derivative of pressure and that of weighted vorticity magnitude. To assess the present approach, the transonic turbulent flow around an NACA 0012 airfoil is performed. Based on the comparison with the experimental data, the accuracy of the present approach is confirmed. According to the high‐resolutional result on the adaptive mesh, the structure of backstep corner vortex, expansion wave and oblique shock wave is distinctly captured. Copyright © 2004 John Wiley & Sons, Ltd.
Molecular pathogenesis of uterine smooth muscle tumors from transcriptional profiling
Authors: Quade Bradley J. , Wang Tao‐Yeuan , Sornberger Kris , Cin Paola Dal , Mutter George L. , Morton Cynthia C.
Published: March 2004

Uterine smooth muscle tumors range from the very common benign leiomyoma to the uncommon, but frequently lethal, leiomyosarcoma. Morphological and clinical differences between these tumors are presumed to result from differences in gene expression. To test this hypothesis, RNAs from four normal uterine myometria, seven uterine leiomyomas, and nine uterine leiomyosarcomas were profiled using microarrays of oligonucleotides representing about 7,000 unique probe sets. RNAs whose levels distinguished any of the three sample types were selected by analysis of variance (ANOVA). The 153 (2.2% of the total) probe sets representing 146 unique genes with the highest test statistic selected for further analysis met minimum ratio and range thresholds between groups. Cluster analysis distinguished benign and malignant samples at the first node, and myometrium and leiomyoma were resolved in a secondary node. Downregulation of specific genes in uterine leiomyosarcoma was the most common pattern of differential gene expression selected by the three‐way ANOVA. Four extrauterine leiomyosarcomas had profiles most similar to that of the uterine leiomyosarcomas. Functional analysis of the 146 genes did not reveal any strong biological theme. These genes were distributed throughout the genome, but there was slight overrepresentation of genes on 1p and 2q. These genes define a tumor signature for uterine smooth muscle neoplasia, and they suggest that the molecular pathways in leiomyoma and leiomyosarcoma are distinct. © 2004 Wiley‐Liss, Inc.
Gene expression profiling and identification of novel prognostic marker genes in neuroblastoma
Authors: Takita Junko , Ishii Masami , Tsutsumi Shuichi , Tanaka Yukichi , Kato Keisuke , Toyoda Yasunori , Hanada Ryoji , Yamamoto Keiko , Hayashi Yasuhide , Aburatani Hiroyuki
Published: March 2004

To investigate the various genetic characteristics of and differences between early‐ and advanced‐stage neuroblastoma (NB) and to identify candidate genes involved in NB progression, we performed DNA microarray analysis on 20 primary tumors. Two‐way clustering analysis based on the expression pattern of approximately 500 of 1,700 genes revealed genetic subgroups in these NB tumors. Although 9 of the 13 early‐stage tumors (69%) and 4 of the 6 advanced‐stage tumors (67%) were classified as being in the same cluster, the remaining tumors showed different expression profiles. This indicates that both the early‐ and advanced‐stage tumors were heterogeneous. Based on the microarray data, we identified the BIRC, CDKN2D, and SMARCD3 genes as those that are predominantly expressed in either the early or the advanced stage of NB. These genes have been reported to be associated with apoptosis, cell cycles, and the transcriptional activator, respectively. To better assess the prognostic value of the expression of these genes in NB, real‐time polymerase chain reaction was carried out on 50 primary tumors. The expression of both the BIRC3 and CDKN2D genes was significantly higher in the early‐stage group than in the advanced‐stage group (P = 0.002 and 0.003, respectively), whereas the expression of the SMARCD3 gene was significantly reduced in the early‐stage group (P = 0.02). Therefore, the BIRC, CDKN2D, and SMARCD3 genes are possible candidates for being novel prognostic markers for NB. © 2004 Wiley‐Liss, Inc.
Type I MOZ/CBP (MYST3/CREBBP) is the most common chimeric transcript in acute myeloid leukemia with t(8;16)(p11;p13) translocation
Authors: Rozman María , Camós Mireia , Colomer Dolors , Villamor Neus , Esteve Jordi , Costa Dolors , Carrió Ana , Aymerich Marta , Aguilar Josep Lluis , Domingo Alícia , Solé Francesc , Gomis Federico , Florensa Lourdes , Montserrat Emili , Campo Elias
Published: March 2004

The t(8;16)(p11;p13) fuses the MOZ (MYST3) gene at 8p11 with CBP (CREBBP) at 16p13 and is associated with an infrequent but well‐defined type of acute myeloid leukemia (AML) that has unique morphocytochemical findings (monocytoid blast morphology with erythrophagocytosis and simultaneously positive for myeloperoxidase and nonspecific esterases). RT‐PCR amplification of MOZ/CBP (MYST3/CREBBP) chimera has proved difficult, with four different transcripts found in four reported cases. We studied 7 AML‐t(8;16) patients, 5 with cytogenetically demonstrated t(8;16) and 2 with similar morphocytochemical and immunophenotypical characteristics. Clinically, 3 cases presented as therapy‐related leukemia. Extramedullar involvement was observed at presentation in 2 patients and coagulopathy in 4. The clinicobiological findings confirmed the distinctiveness of this entity. Of note is the erythrophagocytosis in 5 of 7 cases and the immunological negativity for CD34 and CD117 and positivity for CD56. Using a new RT‐PCR strategy, we were able to amplify a specific band of 212 bp in six cases in which sequence analysis confirmed the presence of the previously described MOZ/CBP fusion transcript type I. This is the largest molecularly studied AML‐t(8;16) series, which demonstrates that MOZ/CBP breakpoints are usually clustered in intron 16 of MOZ and intron 2 of CBP. The newly designed single‐round PCR provides a simple tool for the molecular confirmation of MOZ/CBP rearrangement. © 2004 Wiley‐Liss, Inc.
Novel germ‐line deletion of SNF5/INI1/SMARCB1 gene in neonate presenting with congenital malignant rhabdoid tumor of kidney and brain primitive neuroectodermal tumor
Authors: Kusafuka Takeshi , Miao Jiangyong , Yoneda Akihiro , Kuroda Seika , Fukuzawa Masahiro
Published: March 2004

We describe a neonate who had a rare tumor combination of a malignant rhabdoid tumor of the kidney (MRTK) and a brain primitive neuroectodermal tumor (PNET). Genetic alterations of the SNF5/INI1/SMARCB1 gene were investigated by PCR–single‐strand conformation polymorphism (SSCP), loss of heterozygosity (LOH), sequence, and karyotyping analyses, and the gene expression level was determined by real‐time quantitative RT‐PCR analysis. PCR band signals of each exon of the hSNF5/INI1 were weak or nearly undetectable in both MRTK and PNET, whereas those of the corresponding normal kidney were clearly detected. Aberrantly migrating SSCP bands led to identification of a nucleotide change in intron 8. Although this was regarded as a polymorphism, only the changed nucleotide was observed in the normal kidney of the patient. Allelic states in the parents were heterozygous for the polymorphism in the father and homozygous for the normal sequence in the mother. Thus, it was evident that a substantial genetic part of the maternal normal allele including SNF5/INI1 was deleted as a de novo germ‐line mutation. In both tumors, LOH at microsatellite loci on the long arm of chromosome 22 was evident, and expression of SNF5/INI1 mRNA was drastically decreased compared to that in control tissues (0.7–3.9 vs. 123.6–153.5). Deletion of a substantial genetic part demonstrated in our patient is the novel appearance of a germ‐line deletion of the SNF5/INI1 gene. Additional large somatic deletions resulted in total inactivation of the gene in both tumors. Our patient provides evidence for an important role of SNF5/INI1germ‐line mutation in predisposing patients to multiple rhabdoid tumors. © 2004 Wiley‐Liss, Inc.
Correlation between histone acetylation and expression of the MYO18B gene in human lung cancer cells
Authors: Tani Masachika , Ito Jun , Nishioka Michiho , Kohno Takashi , Tachibana Ken , Shiraishi Masahiko , Takenoshita Seiichi , Yokota Jun
Published: March 2004

Recently, we isolated a candidate tumor‐suppressor gene, MYO18B, which was inactivated in approximately 50% of human lung cancers by deletion, mutation, and promoter methylation. However, more frequent reduction or loss of MYO18B expression and restoration of MYO18B expression by trichostatin A (TSA) treatment suggested the contribution of other mechanisms, especially histone deacetylation, for epigenetic inactivation of the MYO18B gene. In this study, we examined histone modification of the promoter region of the MYO18B gene in 8 human lung cancer cell lines by a chromatin immunoprecipitation assay. In 6 of 7 cell lines with reduced or silenced MYO18B expression, the levels of histones H3 and H4 acetylation surrounding the MYO18B promoter region were lower than those in a cell line with MYO18B expression. By treatment with TSA, the levels of histone H3 and H4 acetylation were increased in all 6 cell lines whose MYO18B expression was restored by TSA, whereas neither H3 nor H4 acetylation was increased in cells whose MYO18B expression was not restored by TSA. Significant correlations were observed between the levels of histone H3/H4 acetylation and MYO18B expression. These results suggest that acetylation of both histones H3 and H4 contributes to regulation of MYO18B expression in lung cancer cells and that histone deacetylation surrounding the promoter region plays an important role in MYO18B silencing and is involved in lung carcinogenesis. © 2004 Wiley‐Liss, Inc.
Oligodendrocytes are susceptible to apoptotic cell death induced by prion protein‐derived peptides
Authors: Sponne Isabelle , Fifre Alexandre , Koziel Violette , Kriem Badreddine , Oster Thierry , Olivier Jean‐Luc , Pillot Thierry
Published: March 2004

Neurodegenerative prion diseases, characterized by a progressive dementia, are associated with the accumulation of abnormal forms of the prion (PrPc) protein, potentially due to an aberrant regulation of PrPc biogenesis and/or topology. One of these forms, termed ctmPrP, displays a transmembrane conformation and might trigger neuronal cell death in Gerstmann‐Straüssler‐Scheinker (GSS) syndrome and other prion‐associated diseases in humans. Although the primary target cells involved in the progression of prion diseases remain unidentified, it was recently suggested that modifications of the oligodendroglial cells occur early in prion diseases. In the present study, we demonstrate that a putative transmembrane domain of the human PrPc, i.e., amino acids 118–135, induces oligodendrocyte (OLG) death in vitro in a time‐ and dose‐dependent manner. The process leading to OLG death and induced by the PrP[118–135] peptide was characterized by DNA fragmentation, cytoskeletal disruption, and caspase activation. Protection against the PrP[118–135] peptide‐induced OLG apoptosis by several antioxidant molecules, such as probucol, propylgallate, and promethazine, suggests that oxidative injuries contribute to the PrP[118–135] cytotoxicity to OLGs. These results suggest a potential pathophysiological role of the ctmPrP‐ and/or PrP fragment‐mediated OLG cytotoxicity in spongiform encephalopathies. © 2004 Wiley‐Liss, Inc.
Odontogenic ghost cell carcinoma
Authors: Goldenberg David , Sciubba James , Tufano Ralph P.
Published: March 2004

Background.

Odontogenic ghost cell carcinoma (OGCC), a malignant counterpart of the calcifying odontogenic cyst (COC), is exceedingly rare. Previous descriptions of this tumor were based on identification of malignant histologic characteristics such as infiltration, cellular pleomorphism, numerous mitoses, and necrosis concurrent with classical benign COC or its solid benign variant, the odontogenic ghost cell tumor.

Methods.

We present a case of a young Asian man who underwent multiple local excisions of a recurring maxillary COC. After one such excision, a rapid onset of painful swelling ensued, and the patient was referred to our institution for definitive surgery.

Results.

The patient underwent a right subtotal maxillectomy. Intraoperatively, a 5‐cm tumor was found to be extending into the right maxillary sinus and nasal cavity. The excised tumor was diagnosed as an OGCC. The tumor was excised with clear margins, and no adjunctive radiotherapy was given. The patient was free of residual or recurrent disease 18 months after surgery.

Conclusions.

On the basis of this case and prior cases found in the literature, OGCCs show a spectrum of growth from slow growing locally invasive tumors to highly aggressive, rapidly growing, infiltrative tumors. Wide local excision with histologically clean margins is the recommended mode of treatment. We recommend close long‐term surveillance of recurrent or long‐standing benign COCs and OGCC. © 2003 Wiley Periodicals, Inc. Head Neck 26: 378–381, 2004
MUC4 and ERBB2 expression in major and minor salivary gland mucoepidermoid carcinoma
Authors: Weed Donald T. , Gomez‐Fernandez Carmen , Pacheco Jeffrey , Ruiz Jose , Hamilton‐Nelson Kara , Arnold David J. , Civantos Francisco J. , Zhang Jin , Yasin Mohammed , Goodwin W. Jarrard , Carraway Kermit L.
Published: March 2004

Background.

Peptide sequence homology between the gene product of human MUC4 and rat sialomucin complex (SMC) has recently been reported. Each contains a mucin subunit with antiadhesive activity linked to the plasma membrane by means of a transmembrane subunit with two epidermal growth factor (EGF)–like domains that act as ligand for ErbB2. This study investigates MUC4 and ErbB2 receptor expression in major and minor salivary gland mucoepidermoid carcinoma and correlates patterns of expression with clinical outcomes.

Methods.

MUC4 antigens and ErbB2 receptor expression are localized by immunohistochemical studies that use archival formalin‐fixed and paraffin‐embedded tissue. Clinical outcomes are determined by retrospective chart review of all patients (n = 28) with available archived pathologic specimens at the University of Miami–affiliated hospitals treated between 1994 and 2000.

Results.

Median survival time was 24 months (range, 2–60 months) among the nine patients who died, whereas median follow‐up time in the remaining 19 patients is 33.4 months (range, 4.7–73 months). A trend toward a reduction in MUC4 antigen expression in high‐grade tumors (55% expression) compared with low‐grade (91% expression) and intermediate‐grade (100% expression) tumors is identified (chi square, p = .0975). Patients with tumors expressing MUC4 antigens are at reduced risk of death (hazard ratio [HR], 0.20; p = .0531). Adjustment for pathologic grade, T stage, and age results in a much higher risk of death for patients whose tumors do not express MUC4 antigens, although this does not meet statistical significance (HR, 26.6; p = .1). Analysis of recurrence adjusting for T stage reveals that patients whose tumors do not express MUC4 antigens are at increased risk of recurrence compared with patients whose tumor expresses MUC4 antigens (HR, 6.37; p = .03). ErbB2 receptor staining is noted in seven of 28 patients, with five of these seven showing 2+ and 3+ membrane‐staining patterns. Adjustment for pathologic grade and age suggests that patients whose tumors express high levels of ErbB2 (2+, 3+) are at increased risk of death compared with patients with low or no expression of ErbB2 (HR, 2.29; p = .32). MUC4 antigen positivity is seen in two of the five cases with 2+ and 3+ staining for ErbB2.

Conclusions.

These findings suggest MUC4 antigen positivity is associated with reduced risk of death and reduced risk of recurrence and may identify a subset of patients with more favorable prognosis. Although limited by small sample size, analysis reveals ErbB2 overexpression is not consistently associated with MUC4 antigen positivity and might be associated with increased risk of death © 2004 Wiley Periodicals, Inc. Head Neck 26: 353–364, 2004
Paranasal sinus tumors: Peter maccallum cancer institute experience
Authors: Porceddu Sandro , Martin Jarad , Shanker Gowrie , Weih LeAnn , Russell Christine , Rischin Danny , Corry June , Peters Lester
Published: March 2004

Background.

The purpose of this study was to evaluate the local control, pattern of recurrence, overall survival, and prognostic factors of patients with squamous cell carcinoma (SCC), adenocarcinoma, and undifferentiated carcinoma of the paranasal sinuses (PNS) and nasal cavity (NC) presenting to our center for curative treatment over a 10‐year period.

Methods.

Between 1991 and 2000, 60 patients with SCC (n= 32), adenocarcinoma (n= 25), and undifferentiated carcinoma (n= 3) of the PNS or NC were identified. Forty patients received surgery and postoperative radiotherapy, four surgery alone; 11, radiotherapy alone; three radical radiotherapy after surgical recurrence; one, chemoradiotherapy and surgery; and one, induction chemotherapy followed by radiotherapy.

Results.

Forty‐seven patients (78%) were seen with T3–4 disease; however, most (92%) were node negative on initial assessment. The predominant failure pattern was local disease persistence or recurrence. The estimated 2‐ and 5‐year local control rates were 63% and 49%, respectively. Orbital and neural invasion significantly affected local control. The estimated 2‐ and 5 year overall survival rates were 57% and 40%, respectively.

Conclusions.

Local failure remains the dominant cause for poor outcome in this group of patients. Because of the proximity of critical normal structures, the ability to perform adequate surgery and to deliver effective radiotherapy is limited in many cases. The use of postoperative concurrent chemoradiotherapy warrants further investigation. © 2004 Wiley Periodicals, Inc.Head Neck26:322–330, 2004.
Use of single nucleotide polymorphism arrays to identify a novel region of loss on chromosome 6q in squamous cell carcinomas of the oral cavity
Authors: Tong Betty C. , Dhir Karan , Ha Patrick K. , Westra William H. , Alter Blanche P. , Sidransky David , Koch Wayne M. , Califano Joseph A.
Published: March 2004

Background.

A subset of patients with oral cavity squamous cell carcinoma(SCC), often of young age yet lacking a history of carcinogen exposure, has been identified, with no clear etiology for tumor development.

Methods.

To identify somatic genetic alterations unique to this patient population, we performed a high throughput single nucleotide polymorphism (SNP) analysis, quantitative PCR of the E6 and E7 regions of human papillomavirus (HPV) 16, sequencing of the IVSF‐4+ locus of the FANC‐C gene, and microsatellite analysis for 18 nonsmoking patients, age 23 to 57 years (median age, 39 years). We compared these results with oral SCC from 17 patients 47 to 81 (median, 64) years of age with significant tobacco exposure (>40 pack‐years) to identify unique genetic alterations for each group.

Results.

SNP analysis demonstrated variable rates of allelic imbalance (AI) and no significant difference in terms of AI patterns between the two groups. However, we found an elevated rate of AI in chromosomal arms 6q (47% [17 of 36]) by performing microsatellite analysis of both groups. Only one tumor demonstrated the presence of HPV 16, and none of the tumors demonstrated mutations in the IVSF‐4+ region of FANC‐C.

Conclusions.

Despite variable marker density, SNP array analysis is an emerging technique for genome‐wide assessment and is a useful tool for discovery of novel sites of allelic loss in oral SCC, including a novel region of allelic loss on chromosome 6q. © 2004 Wiley Periodicals, Inc. Head Neck 26: 345–352, 2004
A randomized controlled trial of colchicine plus ursodiol versus methotrexate plus ursodiol in primary biliary cirrhosis: Ten-year results
Authors: Kaplan Marshall M. , Cheng Steven , Price Lori Lyn , Bonis Peter A. L.
Published: March 2004

Primary biliary cirrhosis frequently progresses despite treatment with ursodeoxycholic acid (UDCA), the only approved therapy. Previous studies suggested that colchicine and methotrexate may improve biochemical tests of liver function, symptoms, and liver histology. The aim of the present study was to determine if the addition of colchicine or methotrexate to UDCA would improve survival free of liver transplantation. Eighty-five patients with histologically confirmed primary biliary cirrhosis whose serum alkaline phosphatase levels were at least twice the normal level and who were not yet candidates for liver transplantation were randomly assigned to receive colchicine or methotrexate in a double-blind study. UDCA was administered to all patients after 2 years. The primary end point was survival free of liver transplantation. Patients were followed up for a total of up to 10 years or until treatment failure. Data were analyzed on an intention-to-treat basis. Transplant-free survival was similar in both groups: 0.57 for colchicine plus UDCA and 0.44 for methotrexate plus UDCA, results that are similar to those predicted by the Mayo prognostic model. Significant improvement in liver biochemical tests and liver histology was observed in a subset of patients in both treatment groups who remained in the study for all 10 years. In conclusion, neither colchcine plus UDCA nor methotrexate plus UDCA improved survival beyond that predicted by the Mayo prognostic model. However, clinical, histologic, and biochemical improvement observed among those who remained in the study for 10 years suggests a possible benefit of these drugs in a subset of patients. (Hepatology 2004;39:915-923.)
Treatment of chronic hepatitis C in HIV/HCV-coinfection with interferon α-2b+ full-course vs. 16-week delayed ribavirin
Authors: Bräu Norbert , Rodriguez-Torres Maribel , Prokupek Dale , Bonacini Maurizio , Giffen Carol A. , Smith Jeffery J. , Frost Kevin R. , Kostman Jay R.
Published: March 2004

Human immunodeficiency virus (HIV)-infected patients increasingly experience the consequences of chronic hepatitis C virus (HCV) coinfection. This trial randomized 107 patients coinfected with HIV and HCV to receive 48 weeks of interferon alfa-2b (IFN) 3 million units three times weekly plus either a full course of ribavirin (RBV) at 800 mg/day (group A; n = 53) or 16 weeks of placebo, followed by RBV (group B; n = 54). The primary endpoint of sustained viral response (SVR) rate (undetectable HCV RNA at posttreatment week 24) was not different between groups A (11.3%) and B (5.6%; P = .32). Within group A, the SVR rate was lower in genotype 1 (2.5%) than in genotypes 2 through 4 (41.7%; P = .002). Fifty-five patients discontinued therapy prematurely, mostly because of adverse events or patient decisions. At treatment week 12, the percentage of CD4+ cells rose in group A (+4.1%; P < .001), but not in group B (−0.3%). A significant proportion (22%) of patients who were HIV viremic at baseline had undetectable HIV RNA at week 12. By week 16, the hemoglobin level decreased more in group A (−2,52 g/dL) than in group B (−1.02 g/dL; P < .001). In group A, the hemoglobin decline was steeper in patients receiving zidovudine (azidothymidine [AZT], −3.64 g/dL vs. no AZT, −2.08 g/dL), and patients receiving zidovudine had more anemia-related RBV dose reductions (AZT, 60% vs. no AZT, 16%). In conclusion, HCV therapy with IFN plus RBV is relatively safe in patients coinfected with HIV and HCV, but frequent treatment discontinuations and anemia-related RBV dose reductions contribute to a poor SVR rate. Control of HIV infection improves rather than worsens during therapy. (Hepatology 2004;39:989-998.)
Immunohistochemical analysis of Mallory bodies in Wilsonian and non-Wilsonian hepatic copper toxicosis
Authors: Müller Thomas , Langner Cord , Fuchsbichler Andrea , Heinz-Erian Peter , Ellemunter Helmut , Schlenck Barbara , Bavdekar Ashish R. , Pradhan Avinash M. , Pandit Anand , Müller-Höcker Josef , Melter Michael , Kobayashi Kunihiko , Nagasaka Hironori , Kikuta Hideaki , Müller Wilfried , Tanner Stuart M. , Sternlieb Irmin , Zatloukal Kurt , Denk Helmut
Published: March 2004

Patients with Wilson's disease (WD), Indian childhood cirrhosis (ICC), and idiopathic copper toxicosis (ICT) develop severe liver disease morphologically characterized by ballooning of hepatocytes, inflammation, cytoskeletal alterations, and Mallory body (MB) formation, finally leading to mostly micronodular cirrhosis. The pathogenesis of MBs in copper toxicosis is still unresolved. Immunohistochemical analysis of MBs in different types of copper intoxication revealed that keratin, p62, and ubiquitin are integral components. Thus MBs associated with copper intoxication resemble those present in alcoholic steatohepatitis (ASH) and nonalcoholic steatohepatitis (NASH). p62 is a multifunctional immediate early gene product that, on the one hand, is involved in stress-induced cell signaling (particularly that of oxidative stress) by acting as an adapter protein linking receptor-interacting protein (RIP) with the atypical protein kinase C. On the other hand, p62 binds with high affinity to polyubiquitin and ubiquitinated proteins. In conclusion, p62 accumulation in WD, ICC, and ICT and deposition in MBs indicates a central role of protein misfolding induced by oxidative stress in copper-induced liver toxicity. By sequestering potentially harmful misfolded ubiquitinated proteins as inert cytoplasmic inclusion bodies (e.g., as MBs), p62 may be a major player in an important cellular rescue mechanism in oxidative hepatocyte injury. (Hepatology 2004;39;963-969.)