bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment decision aids: conceptual issues and future directions
Authors: Charles Cathy , Gafni Amiram , Whelan Tim , O'Brien Mary Ann
Published: April 2005

Background  In the last 10 years, there has been a major growth in the development of treatment decision aids. Multiple goals have been identified for these tools. However, the rationale for and meaning of these goals at the conceptual level, the mechanisms through which decision aids are intended to achieve these goals, and value assumptions underlying the design of aids and associated values clarification exercises have often not been made explicit.

Objective  In this paper, we present ideas to help inform the future development and evaluation of decision aids.

Results  We suggest, (i) that the appropriateness of using any decision aid be assessed within the context of the wider decision‐making encounter within which it is embedded; (ii) that goal setting activities drive measurement activities and not the other way round; (iii) that the rationale for and meaning of goals at the conceptual level, and mechanisms through which they are intended to have an impact be clearly thought through and made explicit; (iv) that value assumptions underlying both decision aids and associated values clarification exercises be communicated to patients; (v) that taxonomies developed and used to classify various types of decision aids include a section on value assumptions underlying each tool; (vi) that further debate and discussion take place on the role of explicit values clarification exercises as a component of or adjunct to treatment decision aids and the feasibility of implementing valid measures.

Conclusion  Further debate and discussion is needed on the above issues.
THE POLITICAL ECONOMY OF SCALE AND EUROPEAN GOVERNANCE1
Authors: JESSOP BOB
Published: April 2005

This paper introduces some concepts for analysing scalar aspects of governance, governance failure, and meta‐governance. There is now a significant corpus of work on multi‐level governance in the European Union as well as an enormous literature on various modes of governance. Although the problem of scale is often posed directly for the EU case (notably in terms of the ‘multi‐level’ character of its political regime), scalar issues are also important for all forms of governance. For effective governance must take account of the specific spatio‐temporalities of its objects and mechanisms as well as the spatio‐temporal location and horizons of action of the subjects involved in its exercise. In particular, among their other relational properties, the objects of governance are more or less embedded in space, place, and scale and linked to distinctive temporal relations and emergent temporalities. This indicates the relevance of a strategic‐relational concern with space, place and scale, with spatial, local and scalar imaginaries, and with attempts to secure spatio‐temporal fixes to facilitate the reproduction of objects of governance. Given space constraints, I focus here on two sets of issues: (i) theoretically, the role of scale, scalar divisions of labour, the relativisation of scale, and multi‐scalar governance; and (ii) substantively, the now paradigmatic case of the European Union as a novel form of multi‐scalar meta‐governance.
WHALE BONES AND SHELL PURPLE‐DYE AT MOTYA (WESTERN SICILY, ITALY)
Authors: REESE DAVID S.
Published: April 2005

Summary. Excavations 30 years ago at sixth–fifth century BC Motya in western Sicily produced a unique assemblage of four Sperm whale vertebrae, crushed purple‐dye shells, and stone tools. The whale vertebrae were the platforms for breaking the shells. Here I discuss recent sightings of Sperm whales in the Mediterranean, the archaeological evidence for whaling in the Mediterranean, and possible whale products available, as well as Italian shell purple‐dye evidence.
POTS AND PITS: DRINKING AND DEPOSITION IN LATE IRON AGE SOUTH‐EAST BRITAIN
Authors: PITTS MARTIN
Published: April 2005

Summary. This paper considers the role of pottery in the Late Iron Age to Roman transition in south‐east Britain. Traditional concern with the significance of Continental imports is rejected in favour of a more holistic and bottom‐up approach giving equal emphasis to locally made forms and imports in complete assemblages. Several stages of inter‐site correspondence analysis are conducted on a range of sites and assemblages in the region. Patterning pertaining to the use and deposition of both imported and local pottery vessels can be seen to contradict simplistic models for ‘Romanization before conquest’. The main conclusions include evidence for the selective disposal of drinking vessels and table wares in pits, the likely widespread consumption of beer as opposed to wine, and the implied importance of indigenous social practices such as feasting and communal drinking.
Six researchers’ contributions to comparative psychology in Japan: 1900–19451
Authors: TAKASUNA MIKI
Published: April 2005

Abstract:  The field of comparative psychology (also called animal psychology) in Japan, as it developed from 1900 to 1945, is reviewed. After evaluating more than 100 research papers (including short abstracts), six researchers were selected as examples of typical Japanese comparative psychologists in approximately the first half of the 20th century. The chosen researchers, K. Masuda, R. Kuroda, S. Kanda, J. G. Yoshioka, S. Takagi, and T. Takemasa, for the most part focused their research in the areas of learning and perception or basic behavioral traits, commonly known as tropism. They studied a wide variety of subjects, from invertebrates to primates, until the end of World War II, when so‐called neo‐behaviorism prevailed.
The evolution of data analyses in Japanese psychology1
Authors: OMI YASUHIRO , KOMATA SEIJI
Published: April 2005

Abstract:  A historical account of data analysis used in the journal, Japanese Journal of Psychology, was examined. Simple statistics were used before 1944. The number of articles that used statistical significance tests increased during the early 1950s, suggesting the occurrence of an inference revolution. This revolution mirrors what happened in the USA 5–10 years earlier. After 1960, the ANOVA overtook the t‐test as the most popular data analysis tool. Multivariate analyses became more widespread after the 1980s. The history of Japanese psychology can be segmented into four periods from the point of view of the statistical methods used: (a) the simple statistics age (1926–1944); (b) the diversification of statistical methods age (1948–1950s); (c) ANOVA, the king of statistics, age (1960s−1970s); and (d) the spread of multivariate analyses age (1980s–present). The use of a qualitative approach in psychology is discussed.
Establishment of new universities and the growth of psychology in postwar Japan1
Authors: FUMINO YOH
Published: April 2005

Abstract:  The quantitative increase in psychologists in postwar Japan was investigated by focusing on the distribution of psychology faculties in universities and graduate schools. The status of psychology in the new teacher‐training system was acknowledged as the institutional basis for this increase. The growth in the number of universities, graduate schools, faculties, and association memberships related to psychology was analyzed. The results indicated that the initial basis for the increase was the new university curriculum of teacher education, which stipulated that educational psychology and related subjects should be compulsory. As a result, new jobs for psychologists were created in most universities. The establishment of graduate schools was another factor that contributed to the increase in psychologists because it provided psychology researchers for newly established universities. In particular, since the 1990s, graduate schools offering courses in clinical psychology and educational psychology have contributed to the increase in psychologists. The meaning of this increase in psychology in Japanese universities during the current period of university reform is discussed.
Preservation of the Fistula for Reconstruction of the Anal Canal and the Anus in Atresia Ani and Rectovestibular Fistula in 2 Dogs
Authors: Mahler Stephan , Williams Gillian
Published: April 2005

Objective—To report a technique for correction of atresia ani and rectovestibular fistula with fistula preservation, and outcome in 2 dogs.

Study Design—Case report.

Animals—Two intact female puppies.

Methods—The fistula was approached by episiotomy. A vertical median perineal incision was made starting dorsal to the anal region and extended to surround the fistula. The rectum and vagina were separated, and the end of the fistula was sutured to the skin.

Results—Early postoperative complications included constipation, fecal incontinence, and perineal soiling, but long‐term outcome was good in both dogs.

Conclusion—With careful dissection, the fistula and internal anal sphincter can be preserved and used in the surgical reconstruction of the anal canal and anus.

Clinical Relevance—Preservation of the fistula may provide an internal sphincter that contributes to a better functional result during correction of atresia ani. A surgical approach that combines episiotomy and perineal incision for separation of the vagina and rectum, and preserves the fistula may decrease the risk of dehiscence.
PERIOD1-Associated Proteins Modulate the Negative Limb of the Mammalian Circadian Oscillator
Authors: Brown Steven A. , Ripperger Juergen , Kadener Sebastian , Fleury-Olela Fabienne , Vilbois Francis , Rosbash Michael , Schibler Ueli
Published: April 2005

The clock proteins PERIOD1 (PER1) and PERIOD2 (PER2) play essential roles in a negative transcriptional feedback loop that generates circadian rhythms in mammalian cells. We identified two PER1-associated factors, NONO and WDR5, that modulate PER activity. The reduction of NONO expression by RNA interference (RNAi) attenuated circadian rhythms in mammalian cells, and fruit flies carrying a hypomorphic allele were nearly arrhythmic. WDR5, a subunit of histone methyltransferase complexes, augmented PER-mediated transcriptional repression, and its reduction by RNAi diminished circadian histone methylations at the promoter of a clock gene.
Insect-Resistant GM Rice in Farmers' Fields: Assessing Productivity and Health Effects in China
Authors: Huang Jikun , Hu Ruifa , Rozelle Scott , Pray Carl
Published: April 2005

Although no country to date has released a major genetically modified (GM) food grain crop, China is on the threshold of commercializing GM rice. This paper studies two of the four GM varieties that are now in farm-level preproduction trials, the last step before commercialization. Farm surveys of randomly selected farm households that are cultivating the insect-resistant GM rice varieties, without the aid of experimental station technicians, demonstrate that when compared with households cultivating non-GM rice, small and poor farm households benefit from adopting GM rice by both higher crop yields and reduced use of pesticides, which also contribute to improved health.
Experimental Verification of Designer Surface Plasmons
Authors: Hibbins Alastair P. , Evans Benjamin R. , Sambles J. Roy
Published: April 2005

We studied the microwave reflectivity of a structured, near perfectly conducting substrate that was designed to verify the existence of a theoretically proposed new class of surface mode. Measurements of the mode's dispersion curve show that it correctly approaches the predicted asymptotic frequency; the curve also agrees well with that derived from a computer simulation. Modeling of the field distribution on resonance provides evidence of strong localization of the electric field at the interface and substantial power flow along the interface, thus verifying the surface plasmon–like nature of the mode.
A Rapid Shift in a Classic Clinal Pattern in
Drosophila
Reflecting Climate Change
Authors: Umina P. A. , Weeks A. R. , Kearney M. R. , McKechnie S. W. , Hoffmann A. A.
Published: April 2005

Geographical clines in genetic polymorphisms are widely used as evidence of climatic selection and are expected to shift with climate change. We show that the classic latitudinal cline in the alcohol dehydrogenase polymorphism of
Drosophila melanogaster
has shifted over 20 years in eastern coastal Australia. Southern high-latitude populations now have the genetic constitution of more northerly populations, equivalent to a shift of 4° in latitude. A similar shift was detected for a genetically independent inversion polymorphism, whereas two other linked polymorphisms exhibiting weaker clinal patterns have remained relatively stable. These genetic changes are likely to reflect increasingly warmer and drier conditions and may serve as sensitive biomarkers for climate change.
Ideals Drowned in the Marketplace
Authors: Shapiro Harold T.
Published: April 2005

University, Inc.
The Corporate Corruption of American Higher Education.
By Jennifer Washburn
. Basic Books, New York, 2005. 346 pp. $26, C$36.95, £19.99. ISBN 0-465-09051-6.

The author argues that corporate intrusion-with its concomitant secrecy, patent monopolies, and exclusive licenses-is undermining academic freedom and scientific inquiry in U.S. universities.
Appreciating Our Usual Guests
Authors: Tuomanen Elaine
Published: April 2005

Microbial Inhabitants of Humans
Their Ecology and Role in Health and Disease.
By Michael Wilson
. Cambridge University Press, New York, 2005. 475 pp. $65, £35. ISBN 0-521-84158-5.

Taking an ecological approach that considers the influence of anatomical and physiological features of the human host as well as the microorganisms' impact on both healthy and impaired individuals, the author surveys microbial communities that inhabit healthy humans.
FLAVOR AND CHIRAL OSCILLATIONS
Authors: BERNARDINI ALEX E. , DE LEO STEFANO
Published: April 2005

We seek a quantum-theoretic expression for the probability that a "fermionic" particle which is initially in a well-defined flavor, linear combination of mass-eigenstates, will be found, at later times, in another flavor state. We approach this problem by using the Dirac equation as evolution equation for the mass-eigenstates. The Dirac formalism is useful and essential in keeping clear many of the conceptual aspects of quantum oscillation phenomena that naturally arise in a relativistic spin one-half particle theory. Our study leads to the conclusion that the fermionic nature of the particles and the interference between positive and negative frequency components of mass-eigenstate wave packets modify the standard oscillation probability, obtained by implicitly assuming a "scalar" nature of the mass-eigenstates. Nevertheless, under particular assumptions, i.e. ultra-relativistic particles, strictly peaked momentum distributions and minimal slippage, these modifications introduce correction factors proportional to [Formula: see text] which are practically un-detectable by any experimental analysis.
PSEUDO-HERMITIAN INTERACTION BETWEEN AN OSCILLATOR AND A SPIN-1/2 PARTICLE IN THE EXTERNAL MAGNETIC FIELD
Authors: MANDAL BHABANI PRASAD
Published: April 2005

We consider a spin-1/2 particle in the external magnetic field which couples to a harmonic oscillator through some pseudo-hermitian interaction. We find that the energy eigenvalues for this system are real even though the interaction is not PT-invariant.
Degradation of extracellular ATP by the retinal pigment epithelium
Authors: Reigada David , Lu Wennan , Zhang Xiulan , Friedman Constantin , Pendrak Klara , McGlinn Alice , Stone Richard A. , Laties Alan M. , Mitchell Claire H.
Published: April 2005

Stimulation of ATP or adenosine receptors causes important physiological changes in retinal pigment epithelial (RPE) cells that may influence their relationship to the adjacent photoreceptors. While RPE cells have been shown to release ATP, the regulation of extracellular ATP levels and the production of dephosphorylated purines is not clear. This study examined the degradation of ATP by RPE cells and the physiological effects of the adenosine diphosphate (ADP) that result. ATP was readily broken down by both cultured human ARPE-19 cells and the apical membrane of fresh bovine RPE cells. The compounds ARL67156 and βγ-mATP inhibited this degradation in both cell types. RT-PCR analysis of ARPE-19 cells found mRNA message for multiple extracellular degradative enzymes; ectonucleotide pyrophosphatase/phosphodiesterase eNPP1, eNPP2, and eNPP3; the ectoATPase ectonucleoside triphosphate diphosphohydrolase NTPDase2, NTPDase3, and some message for NTPDase1. Considerable levels of ADP bathed RPE cells, consistent with a role for NTPDase2. ADP and ATP increased levels of intracellular Ca2+. Both responses were inhibited by thapsigargin and P2Y1 receptor inhibitor MRS 2179. Message for both P2Y1 and P2Y12 receptors was detected in ARPE-19 cells. These results suggest that extracellular degradation of ATP in subretinal space can result in the production of ADP. This ADP can stimulate P2Y receptors and augment Ca2+ signaling in the RPE.
Flow cytometric method for enumeration and characterization of newly released polymorphonuclear leukocytes from the bone marrow using 5′-bromo-2′-deoxyuridine
Authors: Shih Chih-Horng , Whalen Beth A. , Goto Yukinobu , Hogg James C. , van Eeden Stephan F.
Published: April 2005

Inflammation accelerates polymorphonuclear leukocyte (PMN) release from the bone marrow, and these PMNs are implicated in inappropriate tissue injury. We have previously developed a method using 5′-bromo-2′-deoxyuridine (BrdU) to study PMN kinetics using an immunocytochemical grading system of PMN on cytospin slides. The aim of this study was to develop a flow cytometric method to quantify the number of positively stained PMN and grade the intensity of staining for the transit time calculation of PMN through the marrow. Dividing myeloid progenitors in the marrow of rabbits were labeled with a pulse dosage of intravenous BrdU. BrdU-labeled PMN (PMNBrdU) were detected in the circulation using a FITC-conjugated anti-BrdU monoclonal antibody. The PMNBrdU were assigned to five groups according to their FITC intensity, and the transit times of PMN at different stages of development in the marrow were calculated. Results were compared using parallel immunocytochemical analysis of the same samples. In control animals, PMNBrdU in the circulation peaked at 72 h after BrdU labeling with 36.0% of PMN labeled. In normal rabbits, the transit times of PMN through the mitotic pool (49.5 ± 4.2 h) and maturation pool (65.5 ± 3.1 h) correlated well with immunocytochemical analysis and previously published values. Using this method, we demonstrated that exposure to air pollution particles accelerates the release of PMNBrdU from the marrow. We conclude that a flow cytometric approach for identifying BrdU-labeled leukocytes provides an objective and accurate method for studying leukocyte kinetics and behavior.
Fixed points, stability, and harmless perturbations
Authors: Burton TA
Published: April 2005

Much has been written about systems in which each constant is a solution and each solution approaches a constant. It is a small step to conjecture that functions promoting such behavior constitute harmless perturbations of stable equations. That idea leads to a new way of avoiding delay terms in a functional-differential equation. In this paper we use fixed point theory to show that such a conjecture is valid for a set of classical equations.
Invariant approximations, generalized "Equation missing" -contractions, and "Equation missing" -subweakly commuting maps
Authors: Shahzad Naseer
Published: April 2005

We present common fixed point theory for generalized contractive "Equation missing"-subweakly commuting maps and obtain some results on invariant approximation.
The Pertinence of Partners
Authors: Wesely Jennifer K. , Wright James D.
Published: April 2005

This article explores the relationships between homeless women and their intimate partners. Based on results from a focus group of homeless women at a domestic violence shelter and 20 in-depth interviews with women at two centers for the homeless, the authors suggest that the nature of the intimate relationships homeless women have are varied and impact their social exclusion and subsequent homelessness in different ways. For instance, women may become homeless without their partners or with them, by force or by choice. Homeless women may be financially dependent on the partner, but they also may be providing the only income for the family. Ultimately, the authors explicate the complex intersection between women’s homelessness and their adult relationships to add to the understanding of homeless women.
Customer Satisfaction and Word of Mouth
Authors: Anderson Eugene W.
Published: April 2005

Do dissatisfied customers engage in more or less word of mouth than satisfied customers? There is theoretical and empirical support for both possibilities. To better understand this issue, the authors developed a utility-based model of the relationship between customer satisfaction and word of mouth. The hypothesized functional form-an asymmetric U-shape-cannot be rejected based on data from the United States and Sweden. In addition, the estimation results based on the two samples are similar, suggesting that the proposed relationship is generalizable. The findings also indicate that although dissatisfied customers do engage in greater word of mouth than satisfied ones, common suppositions concerning the size of this difference appear to be exaggerated.
Management of leiomyosarcomas of the spermatic cord: the role of reconstructive surgery
Authors: Enoch Stuart , Wharton Simon M , Murray Douglas S
Published: April 2005

Background

Leiomyosarcomas (LMS) of the spermatic cord are extremely rare. Radical inguinal orchiectomy and high ligation of the cord is the standard primary surgical procedure. The extent of surrounding soft tissue excision required and the precise role of adjuvant radiotherapy, however, remains unclear. In addition, recurrence is a commonly encountered problem which might necessitate further radical excision of adjacent soft tissues.

Methods

This article reviews the pathophysiology of spermatic cord leiomyosarcomas (LMS), and discusses the various reconstructive surgical options available to repair the inguinal region and the lower anterior abdominal wall after excision of the tumour and the adjacent soft tissues.

Results

There is paucity of literature on LMS of spermatic cord. The majority of paratesticular neoplasms are of mesenchymal origin and up to 30% of these are malignant. In adults, approximately 10% of spermatic cord sarcomas are LMS. Approximately 50% of these tumours recur loco-regionally following definitive surgery; however, the incidence decreases if resection is followed by adjuvant radiotherapy.

Conclusion

It is therefore important to achieve negative histological margins during the primary surgical procedure, even if adjuvant radiotherapy is instituted. If extensive resection is required, either during the primary procedure or following recurrence, reconstructive surgery may become necessary. This article reviews the pathophysiology of spermatic cord LMS, the reasons for recurrence, and discusses the management options including the role of reconstructive surgery.
Adhesion of the probiotic bacterium Lactobacillus plantarum 299v onto the gut mucosa in critically ill patients: a randomised open trial
Authors: Klarin Bengt , Johansson Marie-Louise , Molin Göran , Larsson Anders , Jeppsson Bengt
Published: April 2005

Introduction

To achieve any possible positive effect on the intestinal mucosa cells it is important that probiotics adhere tightly onto the intestinal mucosa. It has been shown in healthy volunteers that Lactobacillus plantarum 299v (Lp 299v) (DSM 9843), a probiotic bacterium, given orally in a fermented oatmeal formula adheres onto the intestinal mucosa, but whether this also occurs in critically ill patients is unknown.

Methods

After randomisation, nine enterally fed, critically ill patients treated with broad-spectrum antibiotics received an oatmeal formula fermented with Lp 299v throughout their stay in the intensive care unit; eight patients served as controls. Biopsies of the rectal mucosa were made at admission and then twice a week, and the biopsies were analysed blindly.

Results

Four patients in the control group were colonised with Lp 299v at admission but thereafter all their biopsies were negative (Lp 299v is an ingredient in a common functional food, ProViva®, in Sweden). Of the treated patients none was colonised at admission but three patients had Lp 299v adhered on the mucosa from the second or third biopsy and in the following samples.

Conclusion

This study shows that Lp 299v could survive the passage from the stomach to the rectum and was able adhere onto the rectal mucosa also in critically ill, antibiotic-treated patients.
Genome-scale evidence of the nematode-arthropod clade
Authors: Dopazo Hernán , Dopazo Joaquín
Published: April 2005

Background

The issue of whether coelomates form a single clade, the Coelomata, or whether all animals that moult an exoskeleton (such as the coelomate arthropods and the pseudocoelomate nematodes) form a distinct clade, the Ecdysozoa, is the most puzzling issue in animal systematics and a major open-ended subject in evolutionary biology. Previous single-gene and genome-scale analyses designed to resolve the issue have produced contradictory results. Here we present the first genome-scale phylogenetic evidence that strongly supports the Ecdysozoa hypothesis.

Results

Through the most extensive phylogenetic analysis carried out to date, the complete genomes of 11 eukaryotic species have been analyzed in order to find homologous sequences derived from 18 human chromosomes. Phylogenetic analysis of datasets showing an increased adjustment to equal evolutionary rates between nematode and arthropod sequences produced a gradual change from support for Coelomata to support for Ecdysozoa. Transition between topologies occurred when fast-evolving sequences of Caenorhabditis elegans were removed. When chordate, nematode and arthropod sequences were constrained to fit equal evolutionary rates, the Ecdysozoa topology was statistically accepted whereas Coelomata was rejected.

Conclusions

The reliability of a monophyletic group clustering arthropods and nematodes was unequivocally accepted in datasets where traces of the long-branch attraction effect were removed. This is the first phylogenomic evidence to strongly support the 'moulting clade' hypothesis.
A phagocytic cell line markedly improves survival of infected neutropenic mice
Authors: Spellberg Brad J , Collins Mary , French Samuel W , Edwards John E , Fu Yue , Ibrahim Ashraf S
Published: April 2005

Disseminated candidiasis is a frequent infection in neutropenic patients, in whom it causes 50% mortality, despite antifungal therapy. As the duration of neutropenia is the strongest predictor of survival in neutropenic patients with invasive fungal infections, neutrophil transfusions are a logical, therapeutic option. However, significant technical barriers have prevented the clinical use of neutrophil transfusions. To overcome these barriers, we identified a human phagocytic cell line that could be administered to candidemic hosts in lieu of freshly harvested neutrophils. HL-60 cells killed Candida albicans in vitro. Activation of HL-60 cells with dimethyl sulfoxide and retinoic acid abrogated the cells’ proliferation and augmented their killing of C. albicans. Administration of activated HL-60 cells to candidemic, neutropenic mice significantly improved survival (53% vs. 0%). Live HL-60 cells chemotaxed to sites of infection, phagocytized C. albicans, and reduced the fungal burden in key target organs. Although unactivated HL-60 cells also reduced tissue fungal burden in vivo, they did not improve survival as a result of their toxicity in infected mice. In contrast, no toxicity as a result of activated HL-60 cells was observed at up to 2 months of follow-up. To our knowledge, this is the first description of a cell line-based immunotherapy for an infectious disease. With further refinements, activated HL-60 cells have the potential to overcome the technical barriers to neutrophil transfusions.
Time-course expression of Toll-like receptors 2 and 4 in inflammatory bowel disease and homeostatic effect of VIP
Authors: Gomariz Rosa P , Arranz Alicia , Abad Catalina , Torroba Marta , Martinez Carmen , Rosignoli Florencia , Garcia-Gómez Maria , Leceta Javier , Juarranz Yasmina
Published: April 2005

Toll-like receptor 2 (TLR2) and -4 mediate signals from a great variety of bacterial gut products, giving the host a panel of microbe-recognizing receptors. Under homeostatic conditions, TLRs act as protective receptors of the intestinal epithelium. When homeostasis is disrupted in diseases such as inflammatory bowel disease, TLR2 and -4 are deregulated. Our study demonstrates, by using a trinitrobenzene sulfonic acid-induced colitis model of Crohn's disease, the constitutive expression and the up-regulation of TLR2 and -4 at messenger and protein levels in colon extracts, as well as in macrophages, dendritic cells, and lymphocytes from mesenteric lymphoid nodes. Vasoactive intestinal peptide (VIP) treatment induced a decrease of TLR2 and -4 expressions approaching ethanol control levels. Our results suggest that VIP modulation of TLR2 and -4 could be explained by two possible mechanisms. The first one would be the secondary reduction of TLR2 and -4 caused by the VIP-mediated decrease of inflammatory mediators such as interleukin-1β and interferon- γ, which synergize with bacterial products, contributing to the amplification of TLR presence in the intestine. The other possible mechanism would involve a VIP-mediated decrease of nuclear factor-κB, which would cause a direct down-regulation of TLR expression. In summary, the resultant physiological effect is the decrease of TLR2 and -4 expressions to homeostatic levels. Our study describes for the first time the role of a peptide present in the gut microenvironment as an effective modulator of the initial steps of acute inflammation, acting at local and systemic levels and leading to the restoration of the homeostasis lost after an established inflammatory/autoimmune disease.
Bcr-Abl regulates osteopontin transcription via Ras, PI-3K, aPKC, Raf-1, and MEK
Authors: Hickey Fionnuala B , England Karen , Cotter Thomas G
Published: April 2005

Chronic myeloid leukemia (CML) is caused by the constitutively active Bcr-Abl tyrosine kinase. This fusion protein is generated by the Philadelphia translocation t(9;22). CML is a progressive condition that invariably advances from a drug-sensitive to a drug-resistant, aggressive, acute leukemia. The mechanisms responsible for this progression are largely unknown; however, in many cases, progression is accompanied by an increase in Bcr-Abl expression. Osteopontin (OPN) expression has been shown to be involved in the progression and increased aggression and invasiveness of many solid tumors. Here, we demonstrate that OPN expression is induced in a model of leukemia, and we describe the identification of specific signaling pathways required for the induction of OPN expression by p210 Bcr-Abl. We have determined that high levels of Bcr-Abl activate a signaling cascade involving the sequential activation of Ras, phosphatidylinositol-3 kinase, atypical protein kinase C, Raf-1, and mitogen-activated protein kinase kinase, leading to the ultimate expression of OPN. Our results suggest that these molecules represent a single pathway and also that there is no redundancy in this pathway, as inhibition of any individual component results in a block in the induction of OPN. The data presented here define for the first time the ability of Bcr-Abl to stimulate the expression of OPN and also identify the signaling pathway involved. This may not only prove important in understanding the mechanisms of progression of CML but also highlights a pathway that may prove significant in many other cases of oncogenesis, where OPN expression is implicated.
Increased Fluorine-18 2-Fluoro-2-Deoxy-D-Glucose (FDG) Uptake in Childhood CNS Tumors Is Correlated With Malignancy Grade: A Study With FDG Positron Emission Tomography/Magnetic Resonance Imaging Coregistration and Image Fusion
Authors: Borgwardt Lise , Højgaard Liselotte , Carstensen Henrik , Laursen Henning , Nowak Markus , Thomsen Carsten , Schmiegelow Kjeld
Published: April 2005

Purpose

Positron emission tomography (PET) has been used in grading of CNS tumors in adults, whereas studies of children have been limited.

Patients and Methods

Nineteen boys and 19 girls (median age, 8 years) with primary CNS tumors were studied prospectively by fluorine-18 2-fluoro-2-deoxy-D-glucose (FDG) PET with (n = 16) or without (n = 22) H215O-PET before therapy. Image processing included coregistration to magnetic resonance imaging (MRI) in all patients. The FDG uptake in tumors was semiquantitatively calculated by a region-of-interest–based tumor hotspot/brain index. Eight tumors without histologic confirmation were classified as WHO grade 1 based on location, MRI, and clinical course (22 to 42 months).

Results

Four grade 4 tumors had a mean index of 4.27 ± 0.5, four grade 3 tumors had a mean index of 2.47 ± 1.07, 10 grade 2 tumors had a mean index of 1.34 ± 0.73, and eight of 12 grade 1 tumors had a mean index of −0.31 ± 0.59. Eight patients with no histologic confirmation had a mean index of 1.04. For these 34 tumors, FDG uptake was positively correlated with malignancy grading (n = 34; r = 0.72; P < .01), as for the 26 histologically classified tumors (n = 26; r = 0.89; P < .01). The choroid plexus papilloma (n = 1) and the pilocytic astrocytomas (n = 3) had a mean index of 3.26 (n = 38; r = 0.57; P < .01). H215O-uptake showed no correlation with malignancy. Digitally performed PET/MRI coregistration increased information on tumor characterization in 90% of cases.

Conclusion

FDG PET of the brain with MRI coregistration can be used to obtain a more specific diagnosis with respect to malignancy grading. Improved PET/MRI imaging of the benign hypermetabolic tumors is needed to optimize clinical use.
The Combined Percentage of Gleason Patterns 4 and 5 Is the Best Predictor of Cancer Progression After Radical Prostatectomy
Authors: Cheng Liang , Koch Michael O. , Juliar Beth E. , Daggy Joanne K. , Foster Richard S. , Bihrle Richard , Gardner Thomas A.
Published: April 2005

Purpose

Clinical outcome is variable in prostate cancer patients treated with radical prostatectomy. The Gleason histologic grade of prostatic adenocarcinoma is one of the strongest predictors of biologic aggressiveness of prostate cancer. We evaluated the significance of the relative proportion of high-grade cancer (Gleason patterns 4 and/or 5) in predicting cancer progression in prostate cancer patients treated with radical prostatectomy.

Patients and Methods

Radical prostatectomy specimens from 364 consecutive prostate cancer patients were totally embedded and whole mounted. Various clinical and pathologic characteristics were analyzed. All pathologic data, including Gleason grading variables, were collected prospectively.

Results

A multiple-factor analysis was performed that included the combined percentage of Gleason patterns 4 and 5, Gleason score, tumor stage, surgical margin status, preoperative prostate-specific antigen (PSA), extraprostatic extension, and total tumor volume. Using Cox regression analysis with bootstrap resampling for predictor selection, we identified the combined percentage of Gleason patterns 4 and 5 (P < .0001) and total tumor volume (P = .009) as significant predictors of PSA recurrence.

Conclusion

The combined percentage of Gleason patterns 4 and 5 is one of the most powerful predictors of patient outcome, and appears superior to conventional Gleason score in identifying patients at increased risk of disease progression. On the basis of our results, we recommend that the combined percentage of Gleason patterns 4 and 5 be evaluated in radical prostatectomy specimens. The amount of high-grade cancer in a prostatectomy specimen should be taken into account in therapeutic decision making and assessment of patient prognosis.
Mitotic Index and Benefit of Adjuvant Anthracycline-Based Chemotherapy in Patients With Early Breast Cancer
Authors: Andre Fabrice , Khalil Ahmed , Slimane Khemaies , Massard Christophe , Mathieu Marie Christine , Vignot Stéphane , Assi Hazem , Delaloge Suzette , Spielmann Marc
Published: April 2005

Purpose

We have evaluated whether the mitotic index could predict the benefit of adjuvant anthracycline-based chemotherapy in patients with early breast cancer who are eligible for adjuvant chemotherapy according to Saint Gallen guidelines.

Patients and Methods

A total of 937 patients from a single institution were included in two randomized trials that compared adjuvant anthracycline-based chemotherapy with no chemotherapy. These patients account for 83% of the overall population included in these trials. The first trial included premenopausal patients with node-negative disease, and the second one included postmenopausal patients, regardless of lymph node status. The treatment benefit was assessed according to the number of mitoses per field (×400).

Results

The mitotic index was assessable in 888 patients (94%). All the patients presented as either node-positive or an average-risk breast cancer according to 2003 Saint Gallen consensus conference guidelines. The 5-year overall survival rates were 91% and 87% for patients treated or not with adjuvant chemotherapy (P = .09). In patients with low/medium mitotic index (< three mitoses/field; n = 450), the 5-year overall survival rate was 95% for patients treated or not with adjuvant chemotherapy (P = .56). In patients with high mitotic index (≥ three mitoses/field; n = 438), the 5-year overall survival rates were 86% and 79% for patients treated or not treated with adjuvant chemotherapy, respectively (P = .02).

Conclusion

A high mitotic index is associated with the efficacy of adjuvant anthracycline-based chemotherapy in patients eligible for adjuvant chemotherapy in daily practice.
Requirements of genetic interactions betweenSrc42A, armadilloandshotgun, a gene encoding E-cadherin, for normal development inDrosophila
Authors: Takahashi Mayuko , Takahashi Fumitaka , Ui-Tei Kumiko , Kojima Tetsuya , Saigo Kaoru
Published: April 2005

Src42A is one of the two Src homologs in Drosophila. Src42A protein accumulates at sites of cell-cell or cell-matrix adhesion. Anti-Engrailed antibody staining of Src42Aprotein-null mutant embryos indicated that Src42A is essential for proper cell-cell matching during dorsal closure. Src42A, which is functionally redundant to Src64, was found to interact genetically with shotgun, a gene encoding E-cadherin, and armadillo, a Drosophila β-catenin. Immunoprecipitation and a pull-down assay indicated that Src42A forms a ternary complex with E-cadherin and Armadillo,and that Src42A binds to Armadillo repeats via a 14 amino acid region, which contains the major autophosphorylation site. The leading edge of Srcmutant embryos exhibiting the dorsal open phenotype was frequently kinked and associated with significant reduction in E-cadherin, Armadillo and F-actin accumulation, suggesting that not only Src signaling but also Src-dependent adherens-junction stabilization would appear likely to be essential for normal dorsal closure. Src42A and Src64 were required for Armadillo tyrosine residue phosphorylation but Src activity may not be directly involved in Armadillo tyrosine residue phosphorylation at the adherens junction.
Vglut1 and ZnT3 co-targeting mechanisms regulate vesicular zinc stores in PC12 cells
Authors: Salazar Gloria , Craige Branch , Love Rachal , Kalman Daniel , Faundez Victor
Published: April 2005

The lumenal ionic content of an organelle is determined by its complement of channels and transporters. These proteins reach their resident organelles by adaptor-dependent mechanisms. This concept is illustrated in AP-3 deficiencies, in which synaptic vesicle zinc is depleted because the synaptic-vesicle-specific zinc transporter 3 does not reach synaptic vesicles. However, whether zinc transporter 3 is the only membrane protein defining synaptic-vesicle zinc content remains unknown. To address this question, we examined whether zinc transporter 3 and the vesicular glutamate transporter Vglut1 (a transporter that coexists with zinc transporter 3 in brain nerve terminals) were co-targeted to synaptic-like microvesicle fractions in PC12 cells. Deconvolution microscopy and subcellular fractionation demonstrated that these two transporters were present on the same vesicles in PC12 cells. Vglut1 content in synaptic-like microvesicle fractions and brain synaptic vesicles was partially sensitive to pharmacological and genetic perturbation of AP-3 function. Whole-cell flow-cytometry analysis of PC12 cell lines expressing zinc transporter 3, Vglut1 or both showed that vesicular zinc uptake was increased by Vglut1 expression. Conversely, production of zinc transporter 3 increased the vesicular uptake of glutamate in a zinc-dependent fashion. Our results suggest that the coupling of zinc transporter 3 and Vglut1 transport mechanisms regulates neurotransmitter content in secretory vesicles.
14-3-3 and calmodulin control subcellular distribution of Kir/Gem and its regulation of cell shape and calcium channel activity
Authors: Béguin Pascal , Mahalakshmi Ramasubbu N. , Nagashima Kazuaki , Cher Damian H. K. , Takahashi Akira , Yamada Yuichiro , Seino Yutaka , Hunziker Walter
Published: April 2005

Individual members of the RGK family of Ras-related GTPases, which comprise Rad, Gem/Kir, Rem and Rem2, have been implicated in important functions such as the regulation of voltage-gated calcium channel activity and remodeling of cell shape. The GTPase Kir/Gem inhibits the activity of calcium channels by interacting with the β-subunit and also regulates cytoskeleton dynamics by inhibiting the Rho-Rho kinase pathway. In addition, Kir/Gem interacts with 14-3-3 and calmodulin, but the significance of this interaction on Kir/Gem function is poorly understood. Here, we present a comprehensive analysis of the binding of 14-3-3 and calmodulin to Kir/Gem. We show that 14-3-3, in conjunction with calmodulin, regulates the subcellular distribution of Kir/Gem between the cytoplasm and the nucleus. In addition, 14-3-3 and calmodulin binding modulate Kir/Gem-mediated cell shape remodeling and downregulation of calcium channel activity. Competition experiments show that binding of 14-3-3, calmodulin and calcium channel β-subunits to Kir/Gem is mutually exclusive, providing a rationale for the observed regulatory effects of 14-3-3 and calmodulin on Kir/Gem localization and function.
Time-Motion Analysis of 6 Cystic Fibrosis Mutation Detection Systems
Authors: Krafft Amy E , Lichy Jack H
Published: April 2005

Background: A dramatic increase in requests for routine cystic fibrosis (CF) carrier screening prompted us to conduct a time-motion analysis comparing commercially available CF testing platforms. Questions addressed in the study included: (a) How much time is required to perform each step involved in carrying out the assay procedure? (b) Which system requires the minimum number of manual manipulations to complete a typical run? (c) What workflow benefits can be achieved by automation?

Methods: We used a 96-sample run for comparisons and analyzed each of the 6 methods to determine the number of pipetting steps and manual manipulations, the labor and instrument time, and the total time required to perform the assay. The survey participants included a staff of 4 technologists who perform complex molecular assays regularly. Time required for each procedure was determined by direct observation and from work logs completed by the technologists.

Results: The total number of pipetting motions varied from 78 to 344. Labor time ranged from 2.6 to 8.4 h, and total assay time from 7.6 to 13.7 h.

Conclusion: Time-motion analysis allowed identification of a method that minimized pipetting motions and thus reduced the risk of repetitive stress injury.
A exposição do contorno lateral direito da veia cava inferior na cirurgia hepática
Authors: Tenório Nailton Jatobá , Goldenberg Alberto , Triviño Tarcísio
Published: April 2005

O conhecimento da relação entre a veia cava inferior e o tecido hepático é fundamental para a sua abordagem durante a cirurgia hepática. Observa-se na literatura dados contraditórios. Objetivo: Pesquisar a sintopia da veia cava inferior, o número de veias confluentes para o contorno direito e a distância do segmento retro-hepático da veia cava inferior. Métodos: Foram estudados 38 fígados humanos, entre 13 e 98 anos de ambos sexos. Obtida a peça anatômica, era dissecada a veia cava inferior, observando-se a sua sintopia com o parênquima hepático. Foram obtidas medidas biométricas da veia cava inferior, como a medida do segmento retro-hepático e anotado o número de veias confluentes para o contorno lateral direito da veia cava inferior. Foi realizado estudo estatístico comparando os dados em relação ao sexo. Resultados: a sintopia do lobo caudado foi determinada como incompleta em 37 (97,4%) casos. A distância total da veia cava inferior em seu segmento retro-hepático foi em média 59,66 mm. O número de veias confluentes foi de 3,44 significantemente maior no sexo masculino (p = 0,027). Conclusões: A sintopia incompleta do lobo caudado é encontrada na maioria dos casos. Este fato facilita o acesso cirúrgico a veia cava inferior retro-hepática quando exposta pelo seu contorno lateral direito. Esta veia apresenta um segmento relativamente curto ocupando um sulco na parte posterior do fígado. Um pequeno número de veias confluem para o contorno direito, significantemente maior no sexo masculino. Deve o cirurgião preocupar-se com a dissecção da região devido a presença destes vasos e a possibilidade de sangramentos volumosos.
Estudo morfométrico do efeito do tenoxicam com água bidestilada ou com cloreto de sódio a 0,9% no endotélio venoso, em coelhos
Authors: Schnaider Taylor Brandão , Silva Alcino Lázaro da , Engelman Miriam de Fátima Brasil , Juliano Yara , Novo Neil Ferreira , Schnaider Gabrielle Sormanti , Schnaider Caroline Sormanti
Published: April 2005

Objetivo: Avaliar, pela morfometria, se o tenoxicam com água bidestilada (diluente) ou com cloreto de sódio a 0,9% (NaCl 0,9%) provoca alterações no endotélio venoso. Métodos: Foram utilizados 90 coelhos (Oryctolagus cuniculus), brancos, da linhagem Nova Zelândia, machos, com idade acima de 10 semanas, com peso variando entre 2000 e 3500 gramas, divididos em dois grupos denominados Experimento e Controle, que foram observados nos tempos de 6h, 12h e 24h. Administrou-se nas venae auriculares dextra e sinistra, tenoxicam com seu diluente ou com NaCl 0,9% no grupo Experimento e NaCl 0,9% no grupo Controle. Para análise estatística dos resultados foi aplicada a análise de variância a um critério: a) em separado para cada grupo (Tenoxicam/NaCl 0,9%, Tenoxicam/Diluente e NaCl 0,9%), para comparar as medidas médias dos diâmetros dos núcleos das células endoteliais obtidas nos períodos de observação de 6h, 12h e 24h. Resultados: Observou-se que não ocorreram diferenças significantes entre as medidas médias dos diâmetros nucleares encontradas nos períodos de eutanásia de 6, 12 e 24h, em separado para cada grupo. As medidas médias dos diâmetros nucleares do grupo Controle foram significantemente maiores do que as observadas no grupo Experimento. Conclusão: O tenoxicam, com água bidestilada ou com cloreto de sódio a 0,9%, reduziu os diâmetros dos núcleos das células endoteliais nas venae em que foi injetado.