bluuebunny/crossref_metadata_2025 huggingface dataset:
Collagen‐platelet rich plasma hydrogel enhances primary repair of the porcine anterior cruciate ligament
Authors: Murray Martha M. , Spindler Kurt P. , Abreu Eduardo , Muller John A. , Nedder Arthur , Kelly Mark , Frino John , Zurakowski David , Valenza Maria , Snyder Brian D. , Connolly Susan A.
Published: October 2006

The anterior cruciate ligament (ACL) fails to heal after suture repair. One hypothesis for this failure is the premature loss of the fibrin clot, or provisional scaffolding, between the two ligament ends in the joint environment. To test this hypothesis, a substitute provisional scaffold of collagen–platelet rich plasma (PRP) hydrogel was used to fill the ACL wound site at the time of suture repair and the structural properties of the healing ACLs evaluated 4 weeks after surgery. Bilateral ACL transections were performed in five 30‐kg Yorkshire pigs and treated with suture repair. In each animal, one of the repairs was augmented with placement of a collagen–PRP hydrogel at the ACL transection site, while the contralateral knee had suture repair alone. In addition, six control knees with intact ACLs from three additional animals were used as a control group. No postoperative immobilization was used. After 4 weeks the animals underwent in vivo magnetic resonance imaging to assess the size of the healing ACL, followed by biomechanical testing to determine tensile properties. The supplementation of suture repair with a collagen–PRP hydrogel resulted in significant improvements in load at yield, maximum load, and linear stiffness at 4 weeks. We conclude that use of a stabilized provisional scaffold, such as a collagen–PRP hydrogel, to supplement primary repair of the ACL can result in improved biomechanical properties at an early time point. Further studies to determine the long‐term effect of primary repair enhancement are needed. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 25:81–91, 2007
Detection of Hcv Antigens in Liver Graft: Relevance To the Management of Recurrent Post-Liver Transplant Hepatitis C
Authors: Grassi Alberto , Quarneti Chiara , Ravaioli Matteo , Bianchini Francesco , Susca Micaela , D'Errico Antonia , Piscaglia Fabio , Tamè Maria Rosa , Andreone Pietro , Grazi GianLuca , Galli Silvia , Zauli Daniela , Pinna Antonio D. , Bianchi Francesco B. , Ballardini Giorgio
Published: October 2006

The aim of this study was to evaluate how the immunohistochemical detection of liver hepatitis C virus (HCV) antigens (HCV-Ag) could support the histologic diagnosis and influence the clinical management of post-liver transplantation (LT) liver disease. A total of 215 liver specimens from 152 HCV-positive patients with post-LT liver disease were studied. Histologic coding was: hepatitis (126), rejection (34), undefined (24; coexisting rejection grade I and hepatitis), or other (31). The percentage of HCV-Ag infected hepatocytes were evaluated, on frozen sections, by an immunoperoxidase technique. HCV-Ag were detectable early in 57% of cases within 30 days post-LT, 92% of cases between 31 and 180 days, and 74% of cases after more than 180 days. Overall, HCV-Ag were detected more frequently in histologic hepatitis as compared to rejection (P < 0.0001) with a higher percentage of positive hepatocytes (P < 0.00001). In 16 patients with a high number of HCV-Ag-positive hepatocytes (65%; range 40-90%) a clinical diagnosis of recurrent hepatitis (RHC) was made despite inconclusive histopathologic diagnosis. Multivariate analysis identified the percentage of HCV-Ag-positive hepatocytes and the time post-LT as independent predictors for RHC (P = 0.008 and P = 0.041, respectively) and the number of HCV-Ag-positive hepatocytes ≥50% as the only independent predictor for nonresponse (P < 0.001) in 26 patients treated with α-interferon plus ribavirin. In conclusion, HCV reinfection occurs early post-LT, reaching its peak within 6 months. Immunohistochemical detection of post-LT HCV reinfection support the diagnosis of hepatitis when the histologic features are not conclusive. A high number of infected cells, independently from the genotype, represents a negative predictive factor of response to antiviral treatment.
Liver Transpl, 2006.

© 2006 AASLD.
Decay estimates for the wave equation of p‐Laplacian type with dissipation of m‐Laplacian type
Authors: Benaissa Abbès , Mokeddem Soufiane
Published: October 2006

In this paper, we study decay properties of solutions to the wave equation of p‐Laplacian type with a weak dissipation of m‐Laplacian type. Copyright © 2006 John Wiley & Sons, Ltd.
Synthesis of well‐defined miktoarm star polymers of poly(dimethylsiloxane) by the combination of chlorosilane and benzyl chloride linking chemistry
Authors: Fragouli Panagiota , Iatrou Hermis , Hadjichristidis Nikos , Sakurai Takuro , Matsunaga Yosuke , Hirao Akira
Published: October 2006

A series of novel four‐arm A2B2 and A2BC and five‐arm A2B2C miktoarm star polymers, where A is poly(dimethylsiloxane) (PDMS), B is polystyrene (PS), and C is polyisoprene (PI), were successfully synthesized by the combination of chlorosilane and benzyl chloride linking chemistry. This new and general methodology is based on the linking reaction of in‐chain benzyl chloride functionalized poly(dimethylsiloxane) (icBnCl–PDMS) with the in‐chain diphenylalkyl (icD) living centers of PS‐DLi‐PS, PS‐DLi‐PI, or (PS)2‐DLi‐PI. icBnCl–PDMS was synthesized by the selective reaction of lithium PDMS enolate (PDMSOLi) with the chlorosilane groups of dichloro[2‐(chloromethylphenyl)ethyl]methylsilane, leaving the benzyl chloride group intact. The icD living polymers, characterized by the low basicity of DLi to avoid side reactions with PDMS, were prepared by the reaction of the corresponding living chains with the appropriate chloro/bromo derivatives of diphenylethylene, followed by a reaction with BuLi or the living polymer. The combined molecular characterization results of size exclusion chromatography, 1H NMR, and right‐angle laser light scattering revealed a high degree of structural and compositional homogeneity in all miktoarm stars prepared. The power of this general approach was demonstrated by the synthesis of a morphologically interesting complex miktoarm star polymer composed of two triblock terpolymer (PS‐b‐PI‐b‐PDMS) and two diblock copolymer (PS‐b‐PI) arms. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 6587–6599, 2006
Multiple‐arm superiority and non‐inferiority designs with various endpoints
Authors: Chang Mark
Published: October 2006

Multiple‐arm dose–response superiority trials are widely studied for continuous and binary endpoints, while non‐inferiority designs have been studied recently in two‐arm trials. In this paper, a unified asymptotic formulation of a sample size calculation for k‐arm (k>0) trials with different endpoints (continuous, binary and survival endpoints) is derived for both superiority and non‐inferiority designs. The proposed method covers the sample size calculation for single‐arm and k‐arm (k⩾2) designs with survival endpoints, which has not been covered in the statistic literature. A simple, closed form for power and sample size calculations is derived from a contrast test. Application examples are provided. The effect of the contrasts on the power is discussed, and a SAS program for sample size calculation is provided and ready to use. Copyright © 2006 John Wiley & Sons, Ltd.
Fetal middle cerebral to uterine artery pulsatility index ratios in normal and pre‐eclamptic pregnancies
Authors: Simanaviciute D. , Gudmundsson S.
Published: October 2006

Objectives

To calculate the normal range for the fetal middle cerebral artery (MCA)/uterine artery pulsatility index (PI) ratio in the third trimester of pregnancy and to assess its value, compared with that of the MCA/umbilical artery PI ratio, in predicting an unfavorable outcome of pregnancies complicated by pre‐eclampsia.

Methods

Doppler blood flow velocimetry of the uterine and umbilical arteries and fetal MCA was performed. We calculated the ratios between 1) the PI of the MCA and the mean PI value of both uterine arteries and 2) the PI of the MCA and the PI of the umbilical artery. All women were examined at or beyond 26 weeks of gestation. A cross‐sectional study of 231 normal pregnancies was conducted to construct the reference range. Values below the 5th percentile or an MCA/umbilical artery PI ratio lower than 1.08 were defined as brain‐sparing. A further 115 pregnancies with pre‐eclampsia (50 mild and 65 severe) were assessed prospectively and the results were related to perinatal outcome. The accuracy of MCA/uterine artery and MCA/umbilical artery PI ratios for prediction of unfavorable pregnancy outcome was compared.

Results

Normal MCA/uterine artery PI ratios decreased with advancing gestational age. Redistribution of the fetal circulation indicated by a low MCA/uterine artery PI ratio was seen in 30% of the mild (n = 15) and 46% of the severe (n = 30) pre‐eclamptic cases. There was a significant difference between those without and those with signs of brain‐sparing, respectively, in mean birth weight (2456.0 vs. 1424.5 g), gestational age at delivery (35.6 vs. 31.3 weeks) and gestational age at the time of examination (34.9 vs. 30.9 weeks). Furthermore, there was a significantly higher rate of small‐for‐gestational‐age (SGA) neonates (57.8% vs. 25.7%), preterm delivery (100% vs. 81.8%) and Cesarean section (90.7% vs. 66.7%) in cases with an MCA/uterine artery PI ratio below the 5th percentile. However, there was no difference between the groups in the rate of low 5‐min Apgar scores, admission to the neonatal intensive care unit, or deliveries before 34 weeks. The MCA/uterine artery and MCA/umbilical artery PI ratios were similar in the prediction of adverse perinatal outcome. Both ratios were better at predicting the outcome of pregnancy than were signs of increased vascular impedance in either the umbilical or uterine arteries.

Conclusions

Normal MCA/uterine artery PI ratio decreases with gestational age. Abnormally low MCA/ uterine artery PI ratios are related to unfavorable pregnancy outcome. The predictive value of the MCA/uterine artery PI ratio is similar to that of the MCA/umbilical artery PI ratio. Copyright © 2006 ISUOG. Published by John Wiley & Sons, Ltd.
The multimedia broadcast/multicast service
Authors: Xylomenos George , Vogkas Vasilis , Thanos George
Published: October 2006

This article provides an overview of the multimedia broadcast/multicast service (MBMS) for universal mobile telecommunications system (UMTS) networks. We first outline the features of UMTS networks as defined by the 3rd generation partnership project (3GPP) in order to provide a background for the discussion to follow. We then present the overall MBMS architecture, the services that it provides to the users and the differences between the broadcast and multicast options. The implementation details of MBMS are explained in terms of the modifications needed to the network, the new signaling procedures required and the impact of MBMS on the radio part of the network. We then describe how the security architecture of UMTS is used to support content protection and key distribution for MBMS groups. We evaluate the prospects of MBMS by comparing it first with IP multicast and then with DVB‐H, considered by many to be the closest competitor of MBMS. Finally, we conclude with a discussion of the technical and business challenges still faced by MBMS. Copyright © 2006 John Wiley & Sons, Ltd.
International Law and the Poststructuralist Challenge
Authors: RASULOV AKBAR
Published: October 2006

Peter Fitzpatrick and Patricia Tuitt (eds.), Critical Beings: Law, Nation and the Global Subject, Aldershot: Ashgate, 2004, 226 pp. (hb).

Sinkwan Cheng (ed.), Law, Justice, and Power: Between Reason and Will, Stanford: Stanford University Press, 2004, 278 pp. (pb).
Soft Law and the Elusive Quest for Sustainable Global Governance
Authors: SINDICO FRANCESCO
Published: October 2006

John J. Kirton and Michael J. Trebilcock (eds.), Hard Choices, Soft Law: Voluntary Standards in Global Trade, Environment and Social Governance, Aldershot: Ashgate Publishing, 2004, ISBN 0754609669, 372 pp.
Mehrebenenanalysen in der psychologischen Forschung
Authors: Nezlek John B. , Schröder-Abé Michela , Schütz Astrid
Published: October 2006

Zusammenfassung. Daten mit Mehrebenenstruktur liegen vor, wenn für jede Versuchsperson eine Vielzahl von Messungen erhoben wird (z.B. in Tagebuchstudien) oder wenn Individuen in Gruppen analysiert werden. Derartige Daten können mit Hilfe von Mehrebenenanalysen ausgewertet werden. Der vorliegende Artikel erläutert das Prinzip der Mehrebenenmodellierung mit Zufallskoeffizienten, nennt Vorteile gegenüber herkömmlichen Analysestrategien und liefert Beispiele aus empirischen Studien. Außerdem wird diskutiert, welche Aspekte bei Mehrebenenanalysen zu beachten sind. Hierzu gehören die Zentrierung von Prädiktoren, die Fixierung von Koeffizienten und die Zahl der Analyseebenen.
Impact of abrupt land cover changes by savanna fire on northern Australian climate
Authors: Görgen K. , Lynch A. H. , Marshall A. G. , Beringer J.
Published: October 2006

Dry season fires are probably the largest natural and anthropogenic disturbance in the Australian tropical savannas. A large fraction of this biome is burned annually. The changed surface properties immediately following a fire and during the regrowth period can lead to a significant modification of the surface‐atmosphere coupling. A fire/regrowth scheme has been developed for the Conformal‐Cubic Atmospheric Model. In a highly constrained setup, it uses forcing perturbations that describe the key impacts of a fire as well as the changes of the parameters controlling a vegetation regrowth function in the soil‐canopy model. In good qualitative agreement with observations, the fires lead to abrupt changes in the surface radiation and energy balances. The boundary layer changes lead subsequently to a regionally significantly stronger convection and an intensification of the cyclonic circulation in the area of the Pilbara heat low. There is an enhanced moisture flux into the lower troposphere that helps to increase precipitation. Given a temporal overlap of the regrowth period and the monsoonal wet season, there is a significant influence on the simulated precipitation associated with the Australian summer monsoon. This is a first step of a sensitivity study on the responses of the simulated earth‐atmosphere system over northern Australia at various scales to the impact of temporary land surface changes induced by savanna fire.
Ru360, a specific mitochondrial calcium uptake inhibitor, improves cardiac post‐ischaemic functional recovery in rats in vivo
Authors: de J García‐Rivas G , Carvajal K , Correa F , Zazueta C
Published: October 2006

Background and purpose:

The mitochondrial permeability transition pore (mPTP), an energy‐dissipating channel activated by calcium, contributes to reperfusion damage by depolarizing the mitochondrial inner membrane potential. As mitochondrial Ca2+ overload is a main inductor of mPTP opening, we examined the effect of Ru360, a selective inhibitor of the mitochondrial calcium uptake system against myocardial damage induced by reperfusion in a rat model.

Experimental approach:

Myocardial reperfusion injury was induced by a 5‐min occlusion of the left anterior descending coronary artery, followed by a 5‐min reperfusion in anaesthetized open‐chest rats. We measured reperfusion‐induced arrhythmias and functions indicative of unimpaired mitochondrial integrity to evaluate the effect of Ru360 treatment.

Key results:

Reperfusion elicited a high incidence of arrhythmias, haemodynamic dysfunction and loss of mitochondrial integrity. A bolus intravenous injection of Ru360 (15‐50 nmol kg−1), given 30‐min before ischaemia, significantly improved the above mentioned variables in the ischaemic/reperfused myocardium. Calcium uptake in isolated mitochondria from Ru360‐treated ventricles was partially diminished, suggesting an interaction of this compound with the calcium uniporter.

Conclusions and implications:

We showed that Ru360 treatment abolishes the incidence of arrhythmias and haemodynamic dysfunction elicited by reperfusion in a whole rat model. Ru360 administration partially inhibits calcium uptake, preventing mitochondria from depolarization by the opening of the mPTP. We conclude that myocardial damage could be a consequence of failure of the mitochondrial network to maintain the membrane potential at reperfusion. Hence, it is plausible that Ru360 could be used in reperfusion therapy to prevent the occurrence of arrhythmia.

British Journal of Pharmacology (2006) 149, 829–837. doi:10.1038/sj.bjp.0706932
Fast-ion D-alpha diagnostic for NSTX
Authors: Heidbrink W. W. , Bell R. E. , Luo Y. , Solomon W.
Published: October 2006

A fast-ion D-alpha (FIDA) diagnostic is under development for the National Spherical Torus Experiment (NSTX). The FIDA technique is a charge-exchange recombination spectroscopy measurement that exploits the large Doppler shift of Balmer-alpha light from energetic hydrogenic atoms to infer the fast-ion density. The principal objective of the NSTX installation is to measure the transport of beam ions caused by fast-ion driven instabilities; detection of perpendicular acceleration of fast ions during high harmonic fast wave heating is another important goal. Recent data from a DIII-D FIDA diagnostic guide the design. The planned NSTX diagnostic consists of two separate instruments focusing on different aspects of the measurement. One instrument uses a transmission grating spectrometer to measure the perpendicular energy spectrum and the spatial profile every 10ms; the anticipated resolution is ∼10keV in energy and ∼5cm in radius. A second instrument employs bandpass filters to detect fast-ion redistribution events with millisecond temporal resolution.
Detailed in situ laser calibration of the infrared imaging video bolometer for the JT-60U tokamak
Authors: Parchamy H. , Peterson B. J. , Konoshima S. , Hayashi H. , Seo D. C. , Ashikawa N. ,   JT-60U Team
Published: October 2006

The infrared imaging video bolometer (IRVB) in JT-60U includes a single graphite-coated gold foil with an effective area of 9×7cm2 and a thickness of 2.5μm. The thermal images of the foil resulting from the plasma radiation are provided by an IR camera. The calibration technique of the IRVB gives confidence in the absolute levels of the measured values of the plasma radiation. The in situ calibration is carried out in order to obtain local foil properties such as the thermal diffusivity κ and the product of the thermal conductivity k and the thickness tf of the foil. These quantities are necessary for solving the two-dimensional heat diffusion equation of the foil which is used in the experiments. These parameters are determined by comparing the measured temperature profiles (for ktf) and their decays (for κ) with the corresponding results of a finite element model using the measured HeNe laser power profile as a known radiation power source. The infrared camera (Indigo/Omega) is calibrated by fitting the temperature rise of a heated plate to the resulting camera data using the Stefan-Boltzmann law.
The Catholic and the Communist Women's Press in Post-War Italy—An Analysis of Cronache and Noi Donne
Authors: Rothenberg Nina
Published: October 2006

This article aims to provide a systematic, comparative analysis of two of the main women's mass publications in order to trace continuities and changes in the development of women's role in the public sphere in Italy. The analysis begins with an elaboration of the social and political context, which is crucial for the understanding of media texts in general. It shows how the existence of only limited political spaces in post-war Italian society due to the polarisation of Catholicism and communism delayed both an open political discourse on women's conditions and the gradual development of an autonomous and lay feminist movement. Noi Donne of Union Donne Italiene (UDI) was closely aligned with and financed by the Italian Communist Party (PCI) and lacked any substantial autonomy until the early 1970s, while Cronache of the Catholic women's organisation Centro Italiano Femminile (CIF) was a faithful instrument for the propagation of those Catholic concepts of femininity that were redefined and reinforced by the Vatican in the Catholic publication Civiltà Cattolica.
Shootin1: a protein involved in the organization of an asymmetric signal for neuronal polarization
Authors: Toriyama Michinori , Shimada Tadayuki , Kim Ki Bum , Mitsuba Mari , Nomura Eiko , Katsuta Kazuhiro , Sakumura Yuichi , Roepstorff Peter , Inagaki Naoyuki
Published: October 2006

Neurons have the remarkable ability to polarize even in symmetrical in vitro environments. Although recent studies have shown that asymmetric intracellular signals can induce neuronal polarization, it remains unclear how these polarized signals are organized without asymmetric cues. We describe a novel protein, named shootin1, that became up-regulated during polarization of hippocampal neurons and began fluctuating accumulation among multiple neurites. Eventually, shootin1 accumulated asymmetrically in a single neurite, which led to axon induction for polarization. Disturbing the asymmetric organization of shootin1 by excess shootin1 disrupted polarization, whereas repressing shootin1 expression inhibited polarization. Overexpression and RNA interference data suggest that shootin1 is required for spatially localized phosphoinositide-3-kinase activity. Shootin1 was transported anterogradely to the growth cones and diffused back to the soma; inhibiting this transport prevented its asymmetric accumulation in neurons. We propose that shootin1 is involved in the generation of internal asymmetric signals required for neuronal polarization.
The Adipokine Visfatin is Markedly Elevated in Obese Children
Authors: Haider Dominik G. , Holzer Gregor , Schaller Georg , Weghuber Daniel , Widhalm Kurt , Wagner Oswald , Kapiotis Stylianos , Wolzt Michael
Published: October 2006

Objective:

The insulin‐mimetic adipocytokine visfatin has been linked to adiposity and the metabolic syndrome.

Design

Cross‐sectional study.

Subjects:

Eighty‐three nondiabetic obese children and 40 healthy controls.

Measurements:

We analyzed plasma visfatin concentrations to assess whether this adipokine is associated with adiposity.

Results:

Plasma visfatin concentrations were nearly 2‐fold higher in obese children (mean, 1.1 ng/mL; 95% CI, 0.2‐6.6) than in controls (0.6 ng/mL, 95% CI, 0.6 to 0.6; P < 0.001). No relationship was detectable between visfatin and other subject characteristics, hsCRP or the lipid profile.

Conclusions:

Visfatin may be involved in the development of metabolic derangements in obese children.
A Prospective Community‐based Study of Gastroenterological Symptoms in School‐age Children
Authors: Saps Miguel , Sztainberg Marcelo , Di Lorenzo Carlo
Published: October 2006

Introduction:

Current knowledge on the prevalence of common gastrointestinal (GI) problems is based on office‐based samples or retrospective questionnaires, leading to possible bias and inaccurate estimates.

Aims:

To examine the prevalence of GI symptoms in school‐age children.

Importance:

This is the first American prospective community study intended to assess the prevalence of common GI symptoms in children.

Patients and Methods:

All fourth‐ and fifth‐grade students from a middle‐size urban school were invited to participate in a prospective cohort pilot study by completing confidential weekly surveys. The survey included a set of 8 age‐appropriate, validated questions assessing the presence and severity of abdominal pain, constipation, diarrhea, nausea, vomiting, chest pain, headaches and limb pain.

Results:

A total of 48 children (32 boys and 16 girls) participated in the study. Data were obtained for 16 weeks on 690 (90.5%) of 768 possible children per week. Children reported at least 1 symptom in 544 (70%) children per week. Headaches were the most common complaint (55% [range, 40%‐72%] children per week). Sixty percent of children (range, 46%‐89%) reported at least 1 GI symptom weekly. The overall prevalence of GI symptoms was the following: abdominal pain 46% (range, 28%‐72%), nausea 28% (range, 17%‐59%), constipation 18% (range, 7%‐39%), diarrhea 17% (range, 11%‐24%) and vomiting 5% (range, 0%‐13%). None of the children missed school because of persistent GI symptoms during the study.

Discussion:

The investigation demonstrates the feasibility of prospective school studies in children. The high prevalence of GI symptoms not interfering with school attendance in children underscores the benign nature of such symptoms in most children.

Conclusion:

Gastrointestinal symptoms are common somatic complaints among school‐age children.
Stimulation of Immunity Without Alteration of Oral Tolerance in Mice Fed With Heat‐Treated Fermented Infant Formula
Authors: Ménard Sandrine , Candalh Céline , Ahmed Melika Ben , Rakotobe Sabine , Gaboriau‐Routhiau Valérie , Cerf‐Bensussan Nadine , Heyman Martine
Published: October 2006

Objectives:

Little information is available on the properties of fermented milk formula intended to healthy infants. This study analyzes the effect of long‐term ingestion of a heat‐treated, fermented milk formula on the development of oral tolerance or systemic immune response to soluble antigens in mice.

Materials and Methods:

The C3H/HeN mice, fed with a heat‐treated fermented (Bifidobacterium breve C50 and Streptococcus thermophilus 065) infant formula (htFF) or a matched control diet (control), were immunized with ovalbumin (OVA) with or without gavage of 20 mg OVA to induce tolerance or immunity, respectively. Systemic and local anti‐OVA immune responses and intestinal barrier function were measured after 5 to 6 weeks.

Results:

Oral tolerance to OVA developed similarly in htFF‐ and control‐fed mice, attested to by the downregulation of OVA‐specific immunoglobulin (Ig) G and IgE after oral OVA administration. In contrast, immunization with OVA led to significantly higher titers in htFF‐fed mice than in control‐fed mice (log2 IgG titers, 16.45 ± 1.24 and 15.46 ± 0.79, respectively; P = 0.012). Jejunal interferon gamma, interleukin 12p40 and interleukin 10 expressions were significantly higher in tolerized mice fed with htFF compared with those fed with the control diet. Mucosal to serosal intact horseradish peroxidase fluxes were lower in htFF‐fed mice than in control‐fed mice (39 ± 8 and 118 ± 38 ng/h.cm2, respectively; P < 0.0001), indicating that the htFF diet reinforces intestinal barrier capacity to macromolecules.

Conclusions:

In mice, htFF strengthens intestinal barrier and enhances systemic immune responses to antigens without interfering with the development of oral tolerance, suggesting a potential beneficial effect in host defence and vaccination.
Pediatric Nonalcoholic Fatty Liver Disease
Authors: Patton Heather M. , Sirlin Claude , Behling Cynthia , Middleton Michael , Schwimmer Jeffrey B. , Lavine Joel E.
Published: October 2006

Although population prevalence is very difficult to establish, nonalcoholic fatty liver disease (NAFLD) is probably the most common cause of liver disease in the preadolescent and adolescent age groups. There seems to be an increase in the prevalence of NAFLD, likely related to the dramatic rise in the incidence of obesity during the past 3 decades. Despite an increase in public awareness, overweight/obesity and related conditions, such as NAFLD, remain underdiagnosed by health care providers. Accurate diagnosis and staging of nonalcoholic steatohepatitis (NASH) requires liver biopsy. The development of noninvasive surrogate markers and the advancements in imaging technology will aid in the screening of large populations at risk for NAFLD. Two distinct histological patterns of NASH have been identified in the pediatric population, and discrete clinical and demographic features are observed in children with these 2 patterns. The propensity for NASH to develop in obese, insulin‐resistant pubertal boys of Hispanic ethnicity or a non‐Hispanic white race may provide clues to the pathogenesis of NAFLD in children. The natural history of pediatric NASH has yet to be defined, but most biopsies in this age group demonstrate some degree of fibrosis. In addition, cirrhosis can be observed in children as young as 10 years. While the optimal treatment of pediatric NAFLD has yet to be determined, lifestyle modification through diet and exercise should be attempted in children diagnosed with NAFLD. A large, multicenter trial of vitamin E and metformin is underway as part of the NASH clinical research network.
Prion protein in cardiac muscle of elk (Cervus elaphus nelsoni) and white-tailed deer (Odocoileus virginianus) infected with chronic wasting disease
Authors: Jewell Jean E. , Brown Jeremy , Kreeger Terry , Williams Elizabeth S.
Published: October 2006

To investigate the possible presence of disease-associated prion protein (PrPd) in striated muscle of chronic wasting disease (CWD)-affected cervids, samples of diaphragm, tongue, heart and three appendicular skeletal muscles from mule deer (Odocoileus hemionus), white-tailed deer (Odocoileus virginianus), elk (Cervus elaphus nelsoni) and moose (Alces alces shirasi) were examined by ELISA, Western immunoblot and immunohistochemistry (IHC). PrPdwas detected in samples of heart muscle from seven of 16 CWD-infected white-tailed deer, including one free-ranging deer, and in 12 of 17 CWD-infected elk, but not in any of 13 mule deer samples, nor in the single CWD-infected moose. For white-tailed deer, PrPdwas detected by Western blot at multiple sites throughout the heart; IHC results on ventricular sections of both elk and white-tailed deer showed positive staining in cardiac myocytes, but not in conduction tissues or nerve ganglia. Levels of PrPdin cardiac tissues were estimated from Western blot band intensity to be lower than levels found in brain tissue. PrPdwas not detected in diaphragm, triceps brachii, semitendinosus, latissiumus dorsi or tongue muscles for any of the study subjects. This is the first report of PrPdin cardiac tissue from transmissible spongiform encephalopathy-infected ruminants in the human food chain and the first demonstration by immunological assays of PrPdin any striated muscle of CWD-infected cervids.
Porcine circovirus type 2 replicase binds the capsid protein and an intermediate filament-like protein
Authors: Timmusk Sirje , Fossum Caroline , Berg Mikael
Published: October 2006

Porcine circovirus type 2 (PCV2) is an important porcine pathogen that establishes persistent subclinical infections but may, on activation, contribute to the development of post-weaning multisystemic wasting syndrome (PMWS). This disease is characterized by weight loss, respiratory or digestive disorders and enlarged lymph nodes with lymphocyte depletion. The molecular mechanisms behind the development of the disease are completely unknown. In order to clarify functions of the different viral proteins and, if possible, to connect these new findings to molecular mechanisms behind the pathogenesis or the viral life cycle, a bacterial two-hybrid screening of a porcine expression library from PK-15A cells was conducted. Using viral proteins corresponding to ORFs 1, 2, 3 and 4 as bait, a number of interactions were identified and two of them were chosen for further characterization. GST pull-down assays confirmed that viral replicase (Rep) interacted with an intermediate filament protein, similar to human syncoilin, and with the transcriptional regulator c-myc. Furthermore, interactions of the viral proteins to each other revealed an interaction between PCV2 Rep and the capsid (Cap) protein and Cap to itself.
Identification of an HLA-A*0201-restricted cytotoxic T-lymphocyte epitope in rotavirus VP6 protein
Authors: Wei Jing , Li Jin-Tao , Zhang Xiao-Ping , Tang Yan , Wang Jing-Xue , Zhang Bei , Wu Yu-Zhang
Published: October 2006

The function of cytotoxic T lymphocytes (CTLs) in rotavirus (RV) infection in humans is poorly understood. To date, no RV-specific human leukocyte antigen (HLA) class I-restricted T-cell epitopes have been described. In this study, four peptides derived from human RV Wa strain VP6 protein were predicted by computer algorithms and verified by an HLA*0201-binding assay. Two peptides with high affinity for HLA-A*0201 molecules were further assessed. The CTLs induced in vitro by P340–348 (TLLANVTAV)-loaded autologous dendritic cells from peripheral blood lymphocytes of HLA-A*0201-matched healthy donors released gamma interferon specifically upon stimulation with P340–348-loaded T2 cells. The CTLs lysed both P340–348-loaded T2 cells and human RV Wa strain-infected HLA-A*0201+ Caco-2 cells in an antigen-specific and HLA-A*0201-restricted manner. At the same time, P340–348 was shown to be immunogenic in vivo in HLA-A*0201/Kb transgenic mice. It is proposed that P340–348 is an HLA-A*0201-restricted CTL epitope.
Cap-dependent and hepatitis C virus internal ribosome entry site-mediated translation are modulated by phosphorylation of eIF2α under oxidative stress
Authors: MacCallum Paul R. , Jack Samantha C. , Egan Philip A. , McDermott Benjamin T. , Elliott Richard M. , Chan Shiu-Wan
Published: October 2006

Chronic hepatitis C is often associated with oxidative stress.Hepatitis C virus(HCV) utilizes an internal ribosome entry site (IRES) element for translation, in contrast to cap-dependent translation of the majority of cellular proteins. To understand how virus translation is modulated under oxidative stress, HCV IRES-mediated translation was compared with cap-dependent translation using a bicistronic reporter construct and hydrogen peroxide (H2O2) as a stress inducer. In H2O2-sensitive HeLa cells, H2O2repressed translation in a time- and dose-dependent manner, concomitant with the kinetics of eIF2αphosphorylation. A phosphomimetic of eIF2α, which mimics the structure of the phosphorylated eIF2α, was sufficient to repress translation in the absence of H2O2. In H2O2-resistant HepG2 cells, H2O2activated both HCV IRES-mediated and cap-dependent translation, associated with an increased level of phospho-eIF2α. It was postulated that H2O2might stimulate translation in HepG2 cells via an eIF2α-independent mechanism, whereas the simultaneous phosphorylation of eIF2αrepressed part of the translational activities. Indeed, the translational repression was released in the presence of a non-phosphorylatable mutant, eIF2α-SA, resulting in further enhancement of both translational activities after exposure to H2O2. In HuH7 cells, which exhibited an intermediate level of sensitivity towards H2O2, both HCV IRES-mediated and cap-dependent translational activities were upregulated after treatment with various doses of H2O2, but the highest level of induction was achieved with a low level of H2O2, which may represent the physiological level of H2O2. At this level, the HCV IRES-mediated translation was preferentially upregulated compared with cap-dependent translation.
Mutagenesis analysis of the NS2B determinants of the Alkhurma virus NS2B–NS3 protease activation
Authors: Pastorino Boris A. M. , Peyrefitte Christophe N. , Grandadam Marc , Thill Maxime C. E. , Tolou Hugues J. , Bessaud Maël
Published: October 2006

Alkhurma virus (ALKV) is a tick-borne class 4 flavivirus responsible for several human cases of haemorrhagic fever in Saudi Arabia, with no specific treatment currently available. The viral RNA encodes a serine protease (NS2B–NS3), essential for virus replication in infected cells, that constitutes an attractive target for antiviral compounds. In an attempt to identify residues and motifs on NS2B that are necessary for protease activity of the ALKV NS2B–NS3 complex, a series of modified NS2B–NS3 proteins was constructed, with point mutations on particular residues or with the NS2B domain derived from two different viruses. Four mutants and the two chimeric proteins exhibited reduction of protease activity against BAPNA (a p-nitroanilide substrate). The results demonstrate that tight complementarity of the protein sequences is necessary for NS2B-dependent activation of NS3. The results also determine residues in the ALKV NS2B cofactor essential for protease activation, giving new insights into protease function in flaviviruses.
Human papillomaviruses target the double-stranded RNA protein kinase pathway
Authors: Hebner Christy M. , Wilson Regina , Rader Janet , Bidder Miri , Laimins Laimonis A.
Published: October 2006

The double-stranded RNA protein kinase (PKR) pathway plays a vital role in the innate immune response to viral infection. Activation of PKR following virus entry can lead to a shutdown in translation, thereby inhibiting viral protein synthesis and replication. Little is currently known about whether human papillomaviruses (HPVs) modulate PKR expression and activity. In this study, normal human foreskin keratinocytes (NHKs) transfected stably with the HPV 31 or 16 genomes and cell lines expressing the HPV 16 E6 and E7 oncoproteins were used to examine effects on the PKR pathway. HPV gene products were found to modulate PKR phosphorylation, activity and localization. The levels of total PKR protein were reduced modestly in cells that maintained HPV 16 or 31 episomes through a reduction in PKR transcription. However, levels of phosphorylated PKR were decreased 4-fold through a post-transcriptional mechanism mediated by E6 and E7 that was independent of the transcriptional downregulation mediated by HPV. In response to infection by vesicular stomatitis virus, phosphorylation of eIF2α was blocked in cells expressing HPV oncoproteins, but not in NHKs. Finally, it was observed that the cellular localization of PKR was altered by HPV gene products in HPV raft cultures, as well as HPV-positive patient biopsies. This effect was mediated by the HPV E6 oncoprotein and leads to the co-localization of PKR with P-bodies. These studies demonstrate that high-risk HPVs target the PKR pathway by multiple mechanisms.
Secondary structure of dengue virus type 4 3′ untranslated region: impact of deletion and substitution mutations
Authors: Romero Tammy A. , Tumban Ebenezer , Jun Jeongwon , Lott William B. , Hanley Kathryn A.
Published: October 2006

Several studies have generated computer-based predictions of secondary structure of the 3′ untranslated region (UTR) ofDengue virus(DEN); however, experimental verification of the formation of these structuresin vitrois lacking. This study assessed the congruence of Mfold predictions of secondary structure of the core region of the DEN type 4 3′ UTR with nuclease maps of this region. Maps and predictions were largely consistent. Maps supported the existence of previously predicted pseudoknots and identified putative regions of dynamic folding. Additionally, this study investigated previously identified conserved elements in the flavivirus 3′ UTR that differ among viruses with different modes of transmission. Specific regions of mosquito-borne DEN type 4 were either deleted or replaced with homologous sequences from tick-borneLangat virus. All of these mutations caused substantial distortion of secondary structure, yet viruses carrying these mutations were viable.
Maturation and function of human dendritic cells are inhibited by orf virus-encoded interleukin-10
Authors: Chan Anna , Baird Margaret , Mercer Andrew A. , Fleming Stephen B.
Published: October 2006

Orf virus (ORFV) is a parapoxvirus that infects sheep, goats and man. In humans, the virus induces acute, pustular skin lesions that can develop into a progressive disease. Humans are susceptible to reinfection with ORFV and rare cases of persistent infection have been reported. ORFV encodes several immunomodulators, including a homologue of interleukin-10 (ORFV IL-10), that may explain these phenomena. The immunosuppressive effects of ORFV IL-10 on immature human dendritic cells (DCs) cultured from blood-derived monocytes (MoDCs) were investigated. MoDCs exposed simultaneously to lipopolysaccharide and ORFV IL-10 showed enhanced ovalbumin–FITC uptake and reduced IL-12 expression, indicating inhibition of maturation. Moreover, ORFV IL-10 inhibited the upregulation of DC cell-surface activation and maturation markers MHC II, CD80, CD83 and CD86 and inhibited the capacity of MoDCs to activate CD4+ T cells in an oxidative mitogenesis assay. These findings suggest that ORFV IL-10 may influence the development of acquired immunity in humans by impairing DC function.
Therapeutic targeting of the endothelin a receptor in human nasopharyngeal carcinoma
Authors: Mai Hai‐Qiang , Zeng Zong‐Yuan , Feng Kai‐Tao , Ye Yan‐Li , Zhang Chang‐Qing , Liang Wei‐Jiang , Guo Xiang , Mo Hao‐Yuan , Hong Ming‐Huang
Published: October 2006

The endothelin A receptor (ETAR) autocrine pathway is overexpressed in many malignancies, including nasopharyngeal carcinoma (NPC). In this tumor, ETAR expression is an independent determinant of survival and a robust independent predictor of distant metastasis. To evaluate whether ETAR represents a new target in NPC treatment, we tested the therapeutic role of ETAR in NPC. Cell proliferation was inhibited by the ETAR‐selective antagonist ABT‐627 in two ETAR‐positive NPC cells in a dose‐dependent manner. Proliferation of ETAR‐negative NPC cells was not decreased. ETAR blockade also resulted in sensitization to cisplatin and 5‐fluorouracil‐induced apoptosis. In nude mice, ABT‐627 inhibited the growth of NPC cell xenografts. Combined treatment of ABT‐627 with the cytotoxic drug cisplatin or 5‐fluorouracil produced additive antitumor effects. The antitumor activity of ABT‐627 was demonstrated finally on an experimental lung metastasis by a reduction in the number of tumors. These results support the rationale of combining ABT‐627 with current standard chemotherapy to further improve the therapeutic ratio in the treatment of NPC. (Cancer Sci2006; 97: 1388–1395)
Land use affects rodent communities in Kalahari savannah rangelands
Authors: Blaum Niels , Rossmanith Eva , Jeltsch Florian
Published: October 2006

Shrub encroachment caused by overgrazing has led to dramatic changes of savannah landscapes and is considered one of the most threatening forms of rangeland degradation leading to habitat fragmentation. Although changes to plant assemblages are becoming better known, however, our understanding of how shrub encroachment affects rodent communities is low. In this study, we investigated relative abundance of five rodent species in sixteen southern Kalahari rangelands where shrub cover ranged from low (<5%) to high (>25%). Rodent abundance was determined on three trapping grids (40 × 100 m) for each site. Our results show that increasing shrub cover affected rodent species differently. The relative abundance of hairy‐footed gerbil, short‐tailed gerbil and bushveld gerbil declined with increasing shrub cover, whereas highveld gerbil and striped mouse exhibited hump‐shaped relationships with shrub cover. Overall, species richness decreased with increasing shrub cover and a negative impact of high shrub cover above 15% on rodent abundance was congruent for all species. We conclude that our results support the hypothesis that long‐term heavy grazing that results in area wide shrub encroachment, threatens the diversity of arid environments.
Urodilatin and four cardiac hormones decrease human renal carcinoma cell numbers
Authors: Vesely B. A. , Eichelbaum E. J. , Alli A. A. , Sun Y. , Gower W. R. , Vesely D. L.
Published: October 2006

Background Mortality from renal‐cell cancer remains a significant problem with an estimated 12 600 deaths in the United States in 2005 even with current treatment(s) of surgery, chemotherapy, radiation and immunotherapy. Four cardiac natriuretic peptides, that is, atrial natriuretic peptide, vessel dilator, long‐acting natriuretic peptide and kaliuretic peptide have significant anti‐cancer effects in breast, pancreatic, prostate and colon adenocarcinomas.

Materials and methods These four peptide hormones plus brain natriuretic peptide (BNP), C‐natriuretic peptide (CNP) and urodilatin, a peptide hormone formed in the kidney by a different post‐translational processing of the atrial natriuretic peptide prohormone, were evaluated for their anti‐cancer effects in renal carcinomas.

Results Dose–response curves revealed a significant (P < 0·0001) decrease in human renal carcinoma cells with each 10‐fold increase in concentration from 1 µm to 100 µm of five of these peptide hormones. There was an 81%, 74%, 66%, 70% and 70% elimination within 24 h in renal carcinoma cells secondary to vessel dilator, kaliuretic peptide, urodilatin, atrial natriuretic peptide and long‐acting natriuretic peptide, respectively (P < 0·0001 for each), whereas BNP had no effect and CNP decreased renal cancer cell number by 10% (P = 0·04) at their 100 µm concentrations. Three days after treatment with these peptide hormones, the cancer cells began to proliferate again. The four cardiac hormones and urodilatin decreased DNA synthesis from 65–84% (P < 0·00001), whereas BNP and CNP decreased DNA synthesis 3% and 12% (both non‐significant). Western blots revealed for the first time natriuretic peptide receptors (NPR)‐A, ‐B and ‐C were present in the renal cancer cells.

Conclusions These results indicate that urodilatin and the four cardiac hormones have potent anti‐cancer effects by eliminating up to 81% of renal carcinoma cells within 24 h of treatment.
Brain site‐specific gene expression analysis in Alzheimer's disease patients
Authors: Yokota T. , Mishra M. , Akatsu H. , Tani Y. , Miyauchi T. , Yamamoto T. , Kosaka K. , Nagai Y. , Sawada T. , Heese K.
Published: October 2006

Background  Alzheimer's disease (AD) is an age‐related neurodegenerative disorder that is characterized by a progressive loss of higher cognitive functions. The brain of an individual with AD exhibits extracellular senile plaques (SPs) of aggregated amyloid‐beta peptide (Aβ) and intracellular neurofibrillary tangles (NFTs). Given the critical role of neuronal transport of both proteins and organelles, it is not surprising that perturbation of microtubule‐based transport may play a major role in the pathogenesis of AD.

Materials and methods  We used the cDNA subtraction methodology and in vitro neural cell culture analyses to study the meaning of the brain site‐specific gene expression pattern in cerebral tissue obtained from AD patients and also from control subjects at autopsy.

Results  We observed that cytoskeleton‐associated proteins were down‐regulated in AD subjects. We also noted an altered expression of the microtubule‐associated protein 1B (MAP1B), the heat‐shock protein (HSP)‐90 (a key chaperone molecule), the tripartite motif‐containing proteins (TRIM)‐32/37 (an anti apoptotic enzyme with ubiquitin‐protein ligase activity) and the Reticulon‐3 (a modulator of the amyloid‐precursor‐protein (APP) cleavage) in AD brains. Additional molecular‐ and cell‐biological studies revealed that small interfering RNA (siRNA)‐mediated down‐regulation of MAP1B expression leads to neuronal cell death in vitro.

Conclusion  Altered expression of MAP1B, HSP90, TRIM32/37 and Reticulon‐3 provides new clues by which the ubiquitin‐proteasome‐, the protein‐chaperon‐ and the APP‐processing systems are disturbed in AD, thus, leading to neuritic amyloid plaques and neurofibrillary tangles.