bluuebunny/crossref_metadata_2025 huggingface dataset:
The accessory olfactory bulb in the adult rat: A cytological study of its cell types, neuropil, neuronal modules, and interactions with the main olfactory system
Authors: Larriva‐Sahd Jorge
Published: July 2008

The accessory olfactory bulb (AOB) in the adult rat is organized into external (ECL) and internal (ICL) cellular layers separated by the lateral olfactory tract (LOT). The most superficial layer, or vomeronasal nerve layer, is composed of two fiber contingents that distribute in rostral and caudal halves. The second layer, or glomerular layer, is also divided by a conspicuous invagination of the neuropil of the ECL at the junction of the rostral and caudal halves. The ECL contains eight cell types distributed in three areas: a subglomerular area containing juxtaglomerular and superficial short‐axon neurons, an intermediate area harboring large principal cells (LPC), or mitral and tufted cells, and a deep area containing dwarf, external granule, polygonal, and round projecting cells. The ICL contains two neuron types: internal granule (IGC) and main accessory cells (MACs). The dendrites and axons of LPCs in the two AOB halves are organized symmetrically with respect to an anatomical plane called linea alba. The LPC axon collaterals may recruit adjacent intrinsic, possibly γ‐aminobutyric acid (GABA)‐ergic, neurons that, in turn, interact with the dendrites of the adjacent LPCs. These modules may underlie the process of decoding pheromonal clues. The most rostral ICL contains another neuron group termed interstitial neurons of the bulbi (INBs) that includes both intrinsic and projecting neurons. MACs and INBs share inputs from fiber efferents arising in the main olfactory bulb (MOB) and AOB and send axons to IGCs. Because IGCs are a well‐known source of modulatory inputs to LPCs, both MACs and INBs represent a site of convergence of the MOB with the AOB. J. Comp. Neurol. 510:309–350, 2008. © 2008 Wiley‐Liss, Inc.
Cross‐domain authorization for federated virtual organizations using the myVocs collaboration environment
Authors: Gemmill Jill , Robinson John‐Paul , Scavo Tom , Bangalore Purushotham
Published: July 2008

This paper describes our experiences building and working with the reference implementation of myVocs (my Virtual Organization Collaboration System). myVocs provides a flexible environment for exploring new approaches to security, application development, and access control built from Internet services without a central identity repository. The myVocs framework enables virtual organization (VO) self‐management across unrelated security domains for multiple, unrelated VOs. By leveraging the emerging distributed identity management infrastructure. myVocs provides an accessible, secure collaborative environment using standards for federated identity management and open‐source software developed through the National Science Foundation Middleware Initiative. The Shibboleth software, an early implementation of the Organization for the Advancement of Structured Information Standards Security Assertion Markup Language standard for browser single sign‐on, provides the middleware needed to assert identity and attributes across domains so that access control decisions can be determined at each resource based on local policy. The eduPerson object class for lightweight directory access protocol (LDAP) provides standardized naming, format, and semantics for a global identifier. We have found that a Shibboleth deployment supporting VOs requires the addition of a new VO service component allowing VOs to manage their own membership and control access to their distributed resources. The myVocs system can be integrated with Grid authentication and authorization using GridShib. Copyright © 2008 John Wiley & Sons, Ltd.
Interventions and outcomes for children with dysphagia
Authors: Gisel Erika
Published: July 2008

Feeding problems are common even in typically developing infants and children. However, they are more frequent and persistent in children with developmental disabilities. This article will provide an overview of current literature and a rationale underlying the interventions used for children with cerebral palsy (CP) who have eating impairments (dysphagia). The review is not intended to be exhaustive, but papers were selected that highlight some of the issues and challenges of the field. Normal oral‐motor development is briefly discussed to show how it may inform clinical practice in the understanding of feeding problems. Description of the risk factors and the nature and extent of eating impairments will show how interventions need to be specific to the severity of eating impairments. Examination of sensorimotor therapies, using oral stimulation exercises or an intra‐oral appliance, will highlight the range of their effectiveness, as well as their limitations. Similarly, an examination of tube feeding, used for nutritional rehabilitation of the most severely affected children, will address the benefits, controversies as well as moral issues encountered by caregivers and professionals. Multi‐center studies will be needed to obtain more homogeneous samples, large enough to address questions of early interventions and their subsequent effect on later development. © 2008 Wiley‐Liss, Inc. Dev Disabil Res Rev 2008;14:165–173.
Three‐dimensional vibration characteristics of the permanent magnet–HTSC magnetic bearing
Authors: Ohashi Shunsuke
Published: July 2008

The three‐dimensional vibration of the rotor in a permanent magnet– HTSC magnetic bearing system is studied. We have developed a magnetic bearing system which can revolve at up to 12,000 rpm, and three‐dimensional vibration of the rotor is measured with laser displacement sensors. To consider the rotor vibration in a mechanical resonance state, the static lateral and vertical pinning forces of the magnetic bearing are measured. The results are used to obtain the resonant frequency. There are two factors in the mechanical resonance caused by the magnetic bearing. One is the lateral equivalent spring coefficient and the other is the vertical equivalent spring coefficient. The influence of mechanical resonance caused by the lateral spring coefficient is large, and that of the vertical one is small. The three‐dimensional vibration of the rotor position around the mechanical resonant frequency is measured. Because the revolution of the rotor increases the lateral force to the center, the resonant frequency obtained in a free revolution experiment is larger than that obtained from pinning force measurement. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 165(3): 58–64, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20586
High‐performance pMOSFETs with high Ge fraction strained SiGe‐heterostructure channel and ultrashallow source/drain formed by selective B‐doped SiGe CVD
Authors: Takehiro Shinobu , Sakuraba Masao , Murota Junichi , Tsuchiya Toshiaki
Published: July 2008

The improvement of current drivability and short‐channel effect is very important for ultrasmall MOS device technology. SiGe‐channel pMOSFETs are one of the most promising devices because hole mobility in the SiGe layers is enhanced. In the previous work, it has been reported that Super Self‐aligned Shallow junction Electrode (S3E) MOSFETs formed by selective B‐doped SiGe CVD are effective for the suppression of short‐channel effect. In this paper, it is clarified that the (S3E) pMOSFETs with Si0.65Ge0.35 channel are realized not only with suppression of punch‐through due to the ultrashallow B‐diffused source/drain but also with enhancement of maximum linear transconductance due to the low parasitic resistance, compared to that with the Si channel fabricated by the same process conditions. © 2008 Wiley Periodicals, Inc. Electr Eng Jpn, 165(3): 46–50, 2008; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/eej.20597
Site‐directed mutagenesis of the chemokine receptor CXCR6 suggests a novel paradigm for interactions with the ligand CXCL16
Authors: Petit Sarah J. , Chayen Naomi E. , Pease James E.
Published: July 2008

Chemokine receptor CXCR6 mediates the chemotaxis and adhesion of leukocytes to soluble and membrane‐anchored forms of CXCL16, and is an HIV‐1 co‐receptor. Here, we describe the effects of mutation of acidic extracellular CXCR6 residues on receptor function. Although most CXCR6 mutants examined were expressed at levels similar to wild‐type (WT) CXCR6, an N‐terminal E3Q mutant was poorly expressed, which may explain previously reported protective effects of a similar single nucleotide polymorphism, with respect to late‐stage HIV‐1 infection. In contrast to several other chemokine receptors, mutation of the CXCR6 N terminus and inhibition of post‐translational modifications of this region were without effect on receptor function. Likewise, N‐terminal extension of CXCL16 resulted in a protein with decent potency and efficacy in chemotaxis and not, as anticipated, a CXCR6 antagonist. D176N and E274Q CXCR6 mutants were unable to interact with soluble CXCL16, suggesting a critical role for D176 and E274 in ligand binding. Intriguingly, although unable to interact with soluble CXCL16, the E274Q mutant could promote robust adhesion to membrane‐anchored CXCL16, suggesting that soluble and membrane‐bound forms of CXCL16 possess distinct conformations. Collectively, our data suggest a novel paradigm for the CXCR6:CXCL16 interaction, a finding which may impact the discovery of small‐molecule antagonists of CXCR6.
Pattern recognition of lipase‐catalyzed or chemically interesterified fat blends containing n‐3 polyunsaturated fatty acids
Authors: Pires Ana Sofia , Osório Natália M. , Nascimento Ana Cláudia , van Keulen Frederik , da Fonseca M. Manuela R. , Ferreira‐Dias Suzana
Published: July 2008

The feasibility to discriminate among samples of different fat blends prior and after inorganic or lipase‐catalyzed interesterification, via pattern recognition techniques [principal component analysis (PCA) and discriminant analysis (DA)], was investigated. Blends I and II, consisting of mixtures of palm stearin, palm kernel oil and a concentrate of triacylglycerols (TAG) rich in n‐3 polyunsaturated fatty acids (EPAX 4510TG or EPAX 2050TG) were used. These blends, prior (64 samples) and after interesterification, catalyzed by an immobilized Thermomyces lanuginosa lipase (Lipozyme TL IM, 54 samples) or by sodium methoxide (10 samples), were characterized by their acylglycerol profiles (25 chromatographic peaks) and solid fat content (SFC) at 10, 20, 30 and 35 °C. PCA on the multivariate data (i) showed that the initial samples were characterized by higher SFC and higher contents of high‐melting TAG and (ii) suggested two separate clusters of initial and interesterified samples. DA was performed on the multivariate data to determine which of the 29 variables have discriminative power. When the 124 samples, characterized by their acylglycerols, were grouped into (i) initial and interesterified samples of blends I or II (four groups) or (ii) also by the catalyst used (six groups), 98.4% of the samples were correctly classified.
A Facile Construction of 6‐(Arylmethyl)imidazo[1,2‐a]pyrimidin‐7‐ylamines from Allylamines Derived from Baylis–Hillman Adducts
Authors: Nag Somnath , Mishra Amita , Batra Sanjay
Published: July 2008

A facile and convenient synthesis of substituted imidazo[1,2‐a]pyrimidin‐7‐ylamines from the allylamine derivatives afforded by the Baylis–Hillman acetates of substituted benzaldehydes and heterocyclic aldehydes by treatment with cyanamide is described. Interestingly, the allylamines afforded by heterocyclic aldehydes, which undergo fast Baylis–Hillman reaction, were discovered to undergo a one‐pot reaction, whereas allylamines derived from all other aldehydes reacted by a two‐step procedure.(© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2008)
New electrophoretic and chromatographic techniques for analysis of heparin and heparan sulfate
Authors: Viola Manuela , Vigetti Davide , Karousou Evgenia , Bartolini Barbara , Genasetti Anna , Rizzi Manuela , Clerici Moira , Pallotti Francesco , De Luca Giancarlo , Passi Alberto
Published: July 2008

Heparin (HE) and heparan sulfated glycosaminoglycans are well‐known mediators of tissue development, maintenance and functions; the activities of these polysaccharides are depending mainly on their sulfate substitutions. The HE structure is also a very important feature in antithrombotic drug development, since the antithrombin binding site is composed by sequences of a specific sulfation pattern. The analysis of disaccharide composition is then a fundamental point of all the studies regarding HE/heparan sulfate glycosaminoglycan (and thereby proteoglycan) functions. The present work describes two analytical methods to quantify the disaccharides constituting HE and heparan sulfate chains. The use of PAGE of fluorophore‐labeled saccharides and HPLC coupled with a fluorescence detector allowed in one run the identification of 90–95% of HE disaccharides and 74–100% of rat kidney purified heparan sulfate. Moreover, the protocol here reported avoid the N‐sulfation disaccharides degradation, which may affect N‐sulfated/N‐acetylated disaccharides ratio evaluation. These methods could be also very important in clinical treatments since they are useful for monitoring the availability kinetics of antithrombotic drugs, such as low‐molecular‐weight HEs.
Modification of the immobilized metal affinity electrophoresis using sodium dodecyl sulfate polyacrylamide gel electrophoresis
Authors: Lee Bao‐Shiang , Jayathilaka G. D. Lasanthi P. , Huang Jin‐Sheng , Decresce David , Borgia Jeffrey A. , Zhou Xiaofeng , Gupta Shalini
Published: July 2008

Modification to the original immobilized metal affinity electrophoresis (IMAEP) technique is presented. SDS‐PAGE is used instead of native PAGE for improved extraction of phosphoproteins from a mixture of proteins. Protein samples treated with 2% w/v SDS instead of native sample buffer ensure that proteins are negatively charged. These negative charges on the proteins assure that the proteins migrate electrophoretically towards the anode regardless of their pI values and hence pass through the region embedded with the metal ions. Another benefit of treating proteins with SDS is that it unfolds the phosphoproteins exposing the phosphate groups to facilitate the metal‐phosphate interactions. Phosphorylated ovalbumin can only be extracted after SDS sample buffer treatment. Data show that there is no detrimental effect upon SDS treatment on the extraction of phosphoproteins from a mixture of proteins. Electrophoretic migration of phosphoproteins ceases upon encounter with metal ions like Al+3, Ti+3, Fe+3, Fe+2, and Mn+2 whereas non‐phosphorylated proteins migrate freely.
Capillary electrophoresis of complex natural polysaccharides
Authors: Volpi Nicola , Maccari Francesca , Linhardt Robert J.
Published: July 2008

Complex natural polysaccharides, glycosaminoglycans (GAGs), are a class of ubiquitous macromolecules that exhibit a wide range of biological functions and participate and regulate multiple cellular events and (patho)physiological processes. They are generally present either as free chains (hyaluronic acid and bacterial acidic polysaccharides) or as side chains of proteoglycans (PGs; chondroitin/dermatan sulfate, heparin/heparan sulfate, and keratan sulfate) and are most often found in cell membranes and in the extracellular matrix. The recent emergence of modern analytical tools for their study has produced a virtual explosion in the field of glycomics. CE, due to its high resolving power and sensitivity, has been useful in the analysis of intact GAGs and GAG‐derived oligosaccharides and disaccharides affording concentration and structural characterization data essential for understanding the biological functions of GAGs. In this review, novel off‐line and on‐line CE‐MS and MS/MS methods for screening of GAG‐derived oligosaccharides and disaccharides will be discussed.
Interactions between thrombin and natural products of Millettia speciosa Champ. using capillary zone electrophoresis
Authors: Zhang Shuyu , Yin Ting , Ling Xiaomei , Liang Hong , Zhao Yuying
Published: July 2008

In Chinese medicine Suberect Spatholobus Stem is used to treat menoxenia, blood deficiency, numb paralyses, and so on. In folk, Millettia speciosa is often used as a substitute for Suberect Spatholobus Stem in some areas but it has not been reported whether M. speciosa is the eligible substitute for Suberect Spatholobus Stem or not till now. In this study, a capillary zone electrophoretic method was applied to determinate the interactions between natural products isolated from M. speciosa Champ. and thrombin for the first time. Both qualitative and quantitative characterizations of the molecule–enzyme binding were determined. Twenty ingredients were isolated from M. speciosa Champ. and the results showed that compared with positive and negative control, the compounds YT‐1, YT‐2, YT‐3, YT‐8, YT‐9, YT‐10, YT‐11, YT‐12, YT‐14, YT‐15, YT‐16, and YT‐20 interacted with thrombin while the other eight had no binding to thrombin. The binding constants of the interaction between compounds and thrombin were calculated by the Scatchard analysis formula. Because M. speciosa contains these compounds which have different levels of anticoagulant activity, it may be the eligible substitute for Suberect Spatholobus Stem.
Influence of polymer structure on electroosmotic flow and separation efficiency in successive multiple ionic layer coatings for microchip electrophoresis
Authors: Boonsong Kanokporn , Caulum Meghan M. , Dressen Brian M. , Chailapakul Orawon , Cropek Donald M. , Henry Charles S.
Published: July 2008

The effect of successive multiple ionic layer (SMIL) coatings on the velocity and direction of EOF and the separation efficiency for PDMS electrophoresis microchips was studied using different polymer structures and deposition conditions. To date, the majority of SMIL studies have used traditional CE and fused‐silica capillaries. EOF was measured as a function of polymer structure and number of layers, in one case using the same anionic polymer and varying the cationic polymer and in the second case using the same cationic polymer and varying the anionic polymer. In both situations, the EOF direction reversed with each additional deposited polymer layer. The absolute EOF magnitude, however, did not vary significantly with layer number or polymer structure. Next, different coatings were used to compare separation efficiencies on native and SMIL‐coated PDMS microchips. For native PDMS microchips, the average separation efficiency was 4105 ± 1540 theoretical plates. The addition of two layers of polymer increased the separation efficiency anywhere from two‐ to five‐fold, depending on the polymer structure. A maximum separation efficiency of 12 880 ± 1050 theoretical plates was achieved for SMIL coatings of polybrene (cationic) and dextran sulfate (anionic) polymers after deposition of six total layers. It was also noted that coating improved run‐to‐run consistency of the peaks as noted by a reduction of the RSD of the EOF and separation efficiency. This study shows that the use of polyelectrolyte coatings, irrespective of the polymer structure, generates a consistent EOF in the current experiments and dramatically improves the separation efficiency when compared to unmodified PDMS microchips.
Functional significance of retrieval‐related activity in lateral parietal cortex: Evidence from fMRI and ERPs
Authors: Vilberg Kaia L. , Rugg Michael D.
Published: July 2008

The present study addressed the question whether neural activity in left lateral parietal cortex is modulated by amount of information recollected. In two experiments (one using fMRI and the other ERPs), subjects first studied pairs of pictures presented for either 1 or 6 s. They then performed a standard “Remember/Know” recognition memory test in which the old items comprised one of the pictures from each studied pair. In both experiments, a surprise posttest indicated that subjects recollected more details about the study presentation of the items presented for the longer duration. In the fMRI experiment, recollection‐ and familiarity‐based recognition elicited activity in distinct cortical networks. Additionally, recollection‐related activity in left inferior parietal cortex was of greater magnitude for test items presented for 6 s than for 1 s. In the ERP study the “left‐parietal old/new effect”—a putative correlate of successful recollection—was likewise modulated by amount of information retrieved. Together, these findings provide further support for dual‐process models of recognition memory and add weight to the proposal that retrieval‐related activity in left inferior parietal cortex reflects processes supporting the online representation of retrieved episodic information. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
Parcellation‐dependent small‐world brain functional networks: A resting‐state fMRI study
Authors: Wang Jinhui , Wang Liang , Zang Yufeng , Yang Hong , Tang Hehan , Gong Qiyong , Chen Zhang , Zhu Chaozhe , He Yong
Published: July 2008

Recent studies have demonstrated small‐world properties in both functional and structural brain networks that are constructed based on different parcellation approaches. However, one fundamental but vital issue of the impact of different brain parcellation schemes on the network topological architecture remains unclear. Here, we used resting‐state functional MRI (fMRI) to investigate the influences of different brain parcellation atlases on the topological organization of brain functional networks. Whole‐brain fMRI data were divided into ninety and seventy regions of interest according to two predefined anatomical atlases, respectively. Brain functional networks were constructed by thresholding the correlation matrices among the parcellated regions and further analyzed using graph theoretical approaches. Both atlas‐based brain functional networks were found to show robust small‐world properties and truncated power‐law connectivity degree distributions, which are consistent with previous brain functional and structural networks studies. However, more importantly, we found that there were significant differences in multiple topological parameters (e.g., small‐worldness and degree distribution) between the two groups of brain functional networks derived from the two atlases. This study provides quantitative evidence on how the topological organization of brain networks is affected by the different parcellation strategies applied. Hum Brain Mapp 2009. © 2008 Wiley‐Liss, Inc.
Functional alterations of liver innate immunity of mice with aging in response to CpG-oligodeoxynucleotide
Authors: Kawabata Toshinobu , Kinoshita Manabu , Inatsu Akihito , Habu Yoshiko , Nakashima Hiroyuki , Shinomiya Nariyoshi , Seki Shuhji
Published: July 2008

Immune functions of liver natural killer T (NKT) cells induced by the synthetic ligand α-galactosylceramide enhanced age-dependently; hepatic injury and multiorgan dysfunction syndrome (MODS) induced by ligand-activated NKT cells were also enhanced. This study investigated how aging affects liver innate immunity after common bacteria DNA stimulation. Young (6 weeks) and old (50-60 weeks) C57BL/6 mice were injected with CpG oligodeoxynucleotides (CpG-ODN), and the functions of liver leukocytes were assessed. A CpG-ODN injection into the old mice remarkably increased tumor necrosis factor (TNF) production in Kupffer cells, and MODS and lethal shock were induced, both of which are rarely seen in young mice. Old Kupffer cells showed increased Toll-like receptor-9 expression, and CpG-ODN challenge augmented TNF receptor and Fas-L expression in liver NKT cells. Experiments using mice depleted of natural killer (NK) cells by anti-asialoGM1 antibody (Ab), perforin knockout mice, and mice pretreated with neutralizing interferon (IFN)-γ Ab demonstrated the important role of liver NK cells in antitumor immunity. The production capacities of old mice for IFN-γ, IFN-α, and perforin were much lower than those of young mice, and the CpG-induced antitumor cytotoxicity of liver NK cells lessened. Lethal shock and MODS greatly decreased in old mice depleted/deficient in TNF, FasL, or NKT cells. However, depletion of NK cells also decreased serum TNF levels and FasL expression of NKT cells, which resulted in improved hepatic injury and survival, suggesting that NK cells are indirectly involved in MODS/lethal shock induced by NKT cells. Neutralization of TNF did not reduce the CpG-induced antitumor effect in the liver.

Conclusion:

Hepatic injury and MODS mediated by NKT cells via the TNF and FasL-mediated pathway after CpG injection increased, but the antitumor activity of liver NK cells decreased with aging. (Hepatology 2008.)
The angiogenic makeup of human hepatocellular carcinoma does not favor vascular endothelial growth factor/angiopoietin-driven sprouting neovascularization
Authors: Zeng Wenjiao , Gouw Annette S.H. , van den Heuvel Marius C. , Zwiers Peter J. , Zondervan Pieter E. , Poppema Sibrand , Zhang Nong , Platteel Inge , de Jong Koert P. , Molema Grietje
Published: July 2008

Quantitative data on the expression of multiple factors that control angiogenesis in hepatocellular carcinoma (HCC) are limited. A better understanding of the mechanisms underlying angiogenesis in HCC will improve the rational choice of anti-angiogenic treatment. We quantified gene and protein expression of members of the vascular endothelial growth factor (VEGF) and angiopoietin systems and studied localization of VEGF, its receptors VEGFR-1 and VEGFR-2, Angiopoietin (Ang)-1 and Ang-2, and their receptor, in HCC in noncirrhotic and cirrhotic livers. We employed real-time reverse transcription polymerase chain reaction (RT-PCR), western blot, and immunohistology, and compared the outcome with highly angiogenic human renal cell carcinoma (RCC). HCC in noncirrhotic and cirrhotic livers expressed VEGF and its receptors to a similar extent as normal liver, although in cirrhotic background, VEGFR-2 levels in both tumor and adjacent tissue were decreased. Ang-1 expression was slightly increased compared with normal liver, whereas Tie-2 was strongly down-regulated in the tumor vasculature. Ang-2 messenger RNA (mRNA) levels were also low in HCCs of both noncirrhotic and cirrhotic livers, implying that VEGF-driven angiogenic sprouting accompanied by angiopoietin-driven vascular destabilization is not pronounced. In RCC, VEGF-A levels were one order of magnitude higher. At the same time, endothelially expressed Ang-2 was over 30-fold increased compared with expression in normal kidney, whereas Ang-1 expression was decreased.

Conclusion:

In hepatocellular carcinoma, tumor vascularization is not

per se

VEGF/angiopoietin driven. However, increased CD31 expression and morphological changes representative of sinusoidal capillarization in tumor vasculature indicate that vascular remodeling is taking place. This portends that therapeutic intervention of HCC at the level of the vasculature is optional, and that further studies into the molecular control thereof are warranted. (Hepatology 2008.)
Alpha-lipoic acid decreases hepatic lipogenesis through adenosine monophosphate-activated protein kinase (AMPK)-dependent and AMPK-independent pathways
Authors: Park Keun-Gyu , Min Ae-Kyung , Koh Eun Hee , Kim Hyoun Sik , Kim Mi-Ok , Park Hye-Sun , Kim Yong-Deuk , Yoon Tae-Seung , Jang Byoung Kuk , Hwang Jae Seok , Kim Jae Bum , Choi Hueng-Sik , Park Joong-Yeol , Lee In-Kyu , Lee Ki-Up
Published: July 2008

Fatty liver is common in obese subjects with insulin resistance. Hepatic expression of sterol regulatory element binding protein-1c (SREBP-1c), which plays a major role in hepatic steatosis, is regulated by multiple factors, including insulin, adenosine monophosphate–activated protein kinase (AMPK), liver X receptors (LXRs), and specificity protein 1. Alpha-lipoic acid (ALA), a naturally occurring antioxidant, has been shown to decrease lipid accumulation in skeletal muscle by activating AMPK. Here we show that ALA decreases hepatic steatosis and SREBP-1c expression in rats on a high fat diet or given an LXR agonist. ALA increased AMPK phosphorylation in the liver and in cultured liver cells, and dominant-negative AMPK partially prevented ALA-induced suppression of insulin-stimulated SREBP-1c expression. ALA also inhibited DNA-binding activity and transcriptional activity of both specificity protein 1 and LXR.

Conclusion:

These results show that ALA prevents fatty liver disease through multiple mechanisms, and suggest that ALA can be used to prevent the development and progression of nonalcoholic fatty liver disease in patients with insulin resistance. (Hepatology 2008.)
Treating hepatitis C in the prison population is cost-saving
Authors: Tan Jennifer A. , Joseph Tom A. , Saab Sammy
Published: July 2008

The prevalence of chronic hepatitis C infection in U.S. prisons is 12% to 31%. Treatment of this substantial portion of the population has been subject to much controversy, both medically and legally. Studies have demonstrated that treatment of chronic hepatitis C with pegylated interferon (PEG IFN) and ribavirin is a cost-effective measure in the general population; however, no study has addressed whether the same is true of the prison population. The aim of this study was to determine the cost-effectiveness of hepatitis C treatment with PEG IFN and ribavirin in the U.S. prison population. Cost-effectiveness was determined via a decision analysis model employing Markov simulation. The cohort of prisoners had a distribution of genotypes and stages of fibrosis in accordance with prior studies evaluating inmate populations. The probability of transitioning from one health state to another, reinfection rates, in-prison and out-of-prison mortality rates, sustained viral response rates, costs, and quality of life weights were also obtained from the literature. Sensitivity analysis was performed. In a strategy without a pretreatment liver biopsy, treatment was cost-effective for all ages and genotypes. This model was robust to rates of disease progression, mortality rates, reinfection rates, sustained viral response rates, and costs. In a strategy employing a pretreatment liver biopsy, treatment was also cost-saving for prisoners of all ages and genotypes with portal fibrosis, bridging fibrosis, or compensated cirrhosis. Treatment was not cost-effective in patients between the ages of 40 and 49 with no fibrosis and genotype 1.

Conclusion:

Treatment of chronic hepatitis C with PEG IFN and ribavirin in U.S. prisons results in both improved quality of life and savings in cost for almost all segments of the inmate population. If the decision to treat hepatitis C is based on pharmaco-economic measures, this significant proportion of infected individuals should not be denied access to therapy. (Hepatology 2008.)
A study of the energy balance and melt regime on Juncal Norte Glacier, semi‐arid Andes of central Chile, using melt models of different complexity
Authors: Pellicciotti Francesca , Helbing Jakob , Rivera Andrés , Favier Vincent , Corripio Javier , Araos José , Sicart Jean‐Emmanuel , Carenzo Marco
Published: July 2008

We use meteorological data from two automatic weather stations (AWS) on Juncal Norte Glacier, central Chile, to investigate the glacier–climate interaction and to test ablation models of different complexity. The semi‐arid Central Andes are characterized by dry summers, with precipitation close to zero, low relative humidity and intense solar radiation. We show that katabatic forcing is dominant both on the glacier tongue and in the fore field, and that low humidity and absence of clouds cause strong radiative cooling of the glacier surface. Surface albedo is basically constant for snow and ice, because of the scarcity of solid precipitation. The energy balance of the glacier is simulated for a 2‐month period in austral summer using two models of different complexity, which differ in the inclusion of the heat conduction flux into the snowpack and in the parameterization of the incoming longwave radiation. Net shortwave radiation is the dominant component of the energy balance. The sensible heat flux is always positive, while both the net longwave radiation and latent heat flux are negative. Neglecting the subsurface heat flux and corresponding variations in surface temperature leads to an overestimation of ablation of 2% over a total of 3695 mm water equivalent (w.e.) at the end of the season. Correct modelling of incoming longwave radiation is crucial, and we suggest that parameterizations based on vapour pressure and air temperature should be used rather than on computed cloud amount. We also used an enhanced temperature‐index model incorporating the shortwave radiation flux, which has two empirical parameters. We apply it both with values of parameters obtained for Alpine glaciers and recalibrated on Juncal Norte. The model recalibrated against the correct energy balance simulations performs very well. The model parameters respond to the meteorological conditions typical of this climatic setting. Copyright © 2008 John Wiley & Sons, Ltd.
Molecular evidence for a clonal relationship between multiple lesions in patients with unknown primary adenocarcinoma
Authors: Speel Ernst‐Jan M. , van de Wouw Agnes J. , Claessen Sandra M.H. , Haesevoets Annick , Hopman Anton H.N. , van der Wurff Anneke A.M. , Osieka Rainhardt , Buettner Reinhard , Hillen Harry F.P. , Ramaekers Frans C.S.
Published: July 2008

Unknown primary adenocarcinoma (UPA) comprises a group of heterogeneous cancers of great clinical and biological interest. UPA presents as metastatic disease without a detectable primary site after medical workup. Here we investigated whether or not a clonal relationship exists between multiple tumors within individual UPA patients. A molecular resemblance would argue for an early clonal outgrowth of tumor cells from the primary lesion, a mutual feature observed within this group of neoplasms. In 14 patients with UPA multiple tumors, obtained at autopsy, were analyzed by molecular allelotyping and immunohistochemistry. In addition, tumors of 4 patients could be analyzed by comparative genomic hybridization (CGH). Similar genetic and phenotypic profiles were used as indicator for a clonal relationship, whereas different profiles implicate independent tumors. The molecular data indicated that the multiple lesions in the 14 UPA patients, including the primary tumors, are clonally related. In agreement with the theory of tumor progression, some metastatic lesions showed additional genetic alterations besides the characteristics that were shared with the primary tumor. Furthermore, 8 UPA patients had tumors with a high frequency of allelic loss and/or imbalance (FALI; 43–71%), while 6 patients demonstrated a lower FALI (14–29%), suggesting the occurrence of chromosomal instability in the former group. Our data provide molecular evidence for a clonal relationship between multiple metastases and the primary tumor within individual UPA patients, independent of the anatomical origin of the cancer. This finding is in agreement with the suggestion that tumor progression is rapid in UPA patients, limiting the chance of clonal divergence. The identification of 2 groups of UPAs with either a high or low FALI indicates that chromosomal instability is not the only driving force behind early tumor cell dissemination. Thus, other molecular mechanisms must underlie the common biology of these tumors. © 2008 Wiley‐Liss, Inc.
Genetic alterations of HLA‐class II in ovarian cancer
Authors: Kübler Kirsten , Arndt Peter F. , Wardelmann Eva , Landwehr Christina , Krebs Dieter , Kuhn Walther , van der Ven Katrin
Published: July 2008

The immune system controls tumor formation through identification and elimination of cellular alterations. Consequently, cancer development in immune competent hosts depends on strategies to evade the immune system. Modulation of tumor antigen‐specific immune responses by aberrant expression of HLA‐class I and II molecules is well documented in a variety of carcinomas including ovarian cancer. To date, little data are available about molecular mechanisms responsible for altered HLA‐class II phenotypes in tumors. In our sample of 10 Caucasian patients with ovarian carcinoma, a semiquantitative analysis was performed for HLA‐class II loci DRB1 and DQB1 in malignant and normal ovarian tissue. Gene amplifications were identified in 62.5% of analyzed alleles and deletions in 17.5%, demonstrating that genomic aberrations of 6p21.3 are common and that copy number gain is more frequent than loss. Moreover, amplifications are most pronounced in advanced‐stage tumors. To evaluate genotype‐phenotype relation, immunohistochemical analyses were performed and revealed de novo expression of HLA‐class II in 30% of tumors with an inverse association between antigen level and HLA copy number. It remains to be elucidated whether the profound changes of the latter quantities are the result of the host's immunological self‐defense, indicate the presence of an oncogene located within the MHC‐complex or merely reflect the increasing loss of differentiation of the tumor tissue. © 2008 Wiley‐Liss, Inc.
Systemic IGF‐I administration stimulates the in vivo growth of early, but not advanced, renal cell carcinoma
Authors: Rosendahl Ann H. , Holly Jeff M.P. , Celander Mona , Forsberg Göran
Published: July 2008

Insulin‐like growth factor I (IGF‐I) is a potent mitogen and antiapoptotic factor. Although elevated serum IGF‐I levels have been associated with increased cancer risk, it is not yet clear whether IGF‐I sensitivity is sustained throughout tumor progression. To evaluate the biological effects of IGF‐I during renal cell carcinoma (RCC) establishment and progression, we administered recombinant human IGF‐I to severe combined immuno‐deficient mice bearing early or more established Caki‐2 human RCC tumors. IGF‐I significantly enhanced the tumor growth 2.4‐fold when administered early after tumor inoculation. This IGF‐I‐induced growth was accompanied with enhanced tumor cell proliferation, tumor vascularization, as well as increased intratumoral insulin‐like growth factor binding protein 3 (IGFBP‐3) and pSmad2 levels. In contrast, IGF‐I administrated to more established RCC tumors showed no effect on tumor growth, with subsequently much lower Ki‐67, IGFBP‐3 and pSmad2 levels. Taken together, these data suggest that systemic IGF‐I has potent actions during early RCC tumor development with a sustained long‐term effect on proliferation and neovascularization although with progression, later tumors appear to become desensitized to systemic IGF‐I effects. © 2008 Wiley‐Liss, Inc.
Expression and prognostic impact of PRL‐3 in lymph node metastasis of gastric cancer: Its molecular mechanism was investigated using artificial microRNA interference
Authors: Wang Zhao , He Yu‐Long , Cai Shi‐Rong , Zhan Wen‐Hua , Li Zeng‐Rong , Zhu Bao‐He , Chen Chuang‐Qi , Ma Jin‐Ping , Chen Zheng‐Xuan , Li Wen , Zhang Long‐Juan
Published: July 2008

High PRL‐3 expression had been reported to have close association with lymph node metastasis (LNM) of gastric cancer. However, the prognostic significance of highly expressing PRL‐3 in LNM of human gastric cancer and the role in the metastasis remain unclear. Our study examined PRL‐3 expression both in the LNM (n = 107) and in the primary lesion (n = 137) of gastric cancer, and compared the overall survival rates. RNA interference, induced by recombinant plasmid pcDNA.rPRL3‐miR expressing artificial PRL‐3 miRNA, was employed to knockdown PRL‐3 expression in human SGC7901 gastric cancer cells. Invasion assay and migration assay in vitro were conducted to determine the role of PRL‐3 in the metastasis. The role of PRL‐3 in the proliferation of SGC7901 cells and tumor growth were also determined. We observed that high PRL‐3 expression was more frequently detected in the LNM than in the matched primary lesion (72.9 vs. 47.7%, p < 0.001). Furthermore, the overall survival rate of the patients with high expression of PRL‐3 in the LNM was significantly less than those with moderate/low expression (p = 0.003). Importantly, knockdown of PRL‐3 can significantly reduce both invasion and migration potencies of SGC7901 cells (p < 0.001), and significantly suppressed the proliferation of SGC7901 cells and slowed down the tumor growth (p < 0.001). It was concluded that high expression of PRL‐3 in the LNM had a negative impact on the prognosis of the patients, and plays important roles in LNM of gastric cancer and the tumor growth, which can be a potential therapeutic target and a prognostic factor. © 2008 Wiley‐Liss, Inc.
Cancer risks among relatives of children with Hodgkin and non‐Hodgkin lymphoma
Authors: Pang Dong , Alston Robert D. , Eden Tim O.B. , Birch Jillian M.
Published: July 2008

A role for genetic susceptibility in the aetiology of childhood lymphomas was investigated in 454 families of children with histologically confirmed Hodgkin lymphoma (HL) and non‐Hodgkin lymphoma (NHL) from Northwest England. Cancers in parents were obtained from the UK National Health Service Central Register and in other close relatives by interview with the parents. The cancer incidence among relatives was compared with expected incidence based on cancer registry data for England. There were 197 cancers in relatives (SIR 1.0 95% CI 0.8–1.1). In families of children with HL, there was an excess of HL in the first degree relatives (SIR 5.8 95% CI 1.2–16.9). Excesses of HL diagnosed under population median age (SIR 4.1 95% CI 1.1–10.6) were seen among all relatives and relatives of children who were below the median age at diagnosis (SIR 5.5 95% CI 1.1–16.0). In families of children with NHL, there were non‐significant excesses of central nervous system (CNS) tumours in the first degree relatives (SIR 2.9 95% CI 0.8–7.4) and in the second and third degree relatives (SIR 1.5). There were significant excesses of CNS tumours diagnosed under the population median age (SIR 2.8 95% CI 1.1–5.8) in all relatives. Excess CNS tumours were also seen among relatives of children below the median age at diagnosis (SIR 3.2 95% CI 1.1–7.6). In conclusion, genetic susceptibility in some families of children with lymphoma might be operating, but aetiologies in HL and NHL appear to be different. Possible interpretations of our findings, in the context of putative genetic and infectious aetiologies, are discussed. © 2008 Wiley‐Liss, Inc.
Cancer risks in ulcerative colitis patients
Authors: Hemminki Kari , Li Xinjun , Sundquist Jan , Sundquist Kristina
Published: July 2008

Patients diagnosed with ulcerative colitis (UC) are known to be at an increased risk of colorectal and liver cancers and leukemia. UC is an autoimmune disease, which may present a wider spectrum of cancers. We wanted to examine the risk of cancer in a large population of UC patients in order to reach high statistical power. A UC research database was constructed by identifying UC patients from the Swedish Hospital Discharge Register and cancer patients from the Cancer Registry. Follow‐up of 27,606 UC patients hospitalized for the first time during the years 1964–2004 identified 2,058 patients with cancer. Standardized incidence ratios were calculated for cancer in UC patients by comparing to subjects without hospitalization for UC. The novel tumor sites in UC patients included small intestinal (carcinoid), pancreatic, breast and prostate cancers, nonthyroid endocrine gland tumors, non‐Hodgkin lymphoma and multiple myeloma. A total of 11 sites showed an increased risk, which remained at 6 sites when tumors diagnosed in the year of UC hospitalization were excluded; even chronic myeloid leukemia was in excess. Cancer risks depended on the age at first hospitalization for UC. The SIRs for colon, rectal, liver and pancreatic cancers declined by age at hospitalization for UC, while for endocrine tumors the older patients were at higher risk. Our large study identified novel subsequent cancers in UC patients. However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients. © 2008 Wiley‐Liss, Inc.
Upregulated expression of complement inhibitory proteins on bladder cancer cells and anti‐MUC1 antibody immune selection
Authors: Varela Juan Carlos , Atkinson Carl , Woolson Robert , Keane Thomas E. , Tomlinson Stephen
Published: July 2008

Membrane complement inhibitors (CD46, CD55 and CD59) are upregulated in some human cancers indicating that they play a role in immune evasion. We investigated complement inhibitor expression in bladder cancer and examined the hypothesis that selective pressure of an antibody response (anti‐MUC1) results in the upregulated expression of complement inhibitors on tumor cells. Paired samples of tumor and normal tissue from 22 bladder cancer patients were analyzed for expression of MUC1, CD46, CD55 and CD59, and matched serum samples analyzed for anti‐MUC1 IgM and IgG levels. Relationships between anti‐MUC1 antibody levels and complement inhibitor expression were investigated. MUC1 mRNA was upregulated in 86% of tumor samples. CD46 was upregulated in 77%, CD55 in 55% and CD59 in 59% of tumors. Low titer anti‐MUC1 IgM was detected in normal human sera, but was elevated in 41% of the bladder cancer patients. Anti‐MUC1 IgG was virtually absent from normal sera, but present in 32% of the cancer patients. There was a direct relationship between anti‐MUC1 antibody titer and expression level of complement inhibitors. Analysis of the correlation of each antibody with the expression of each complement inhibitor by Spearman's rank test revealed a strong correlation between both anti‐MUC1 IgM and IgG levels and increased expression of CD46 and CD55, and combined anti‐MUC1 IgM/IgG levels correlated with increased expression of all 3 complement inhibitors. In conclusion, the data demonstrate upregulated complement inhibitor expression and the presence of an anti‐MUC1 antibody response in bladder cancer patients and support the hypothesis of antibody‐mediated immune selection. © 2008 Wiley‐Liss, Inc.
The beginning of the end of the lung cancer epidemic in Dutch women?
Authors: Karim‐Kos Henrike E. , Janssen‐Heijnen Maryska L.G. , van Iersel Carola A. , van der Meer Regina M. , de Vries Esther , Coebergh Jan Willem W.
Published: July 2008

In some European countries, female lung cancer mortality and incidence have started to decrease or flatten out, whereas they are still rising in The Netherlands. We present recent mortality and incidence trends of lung cancer and smoking trends in The Netherlands to show the end of the lung cancer epidemic in Dutch women. Lung cancer mortality and incidence rates by gender were analyzed for 4 age groups (20–44, 45–49, 50–54 and 55–59), and smoking prevalence rates were examined for women using joinpoint regression and birth cohort analysis. Data on mortality were collected for the period 1960–2006, incidence for the period 1989–2003 and smoking prevalence for the period 1988–2007. Because of decreasing lung cancer mortality and incidence rates among males and dramatically increasing rates among females, rates of young males were surpassed by those of females after the mid‐1990s. However, although in young women (20–49) mortality increased with 4–5% per year, it flattened out (no significant in‐ or decreases) since 1999. Among older women, mortality rates were still increasing markedly. Mortality rates and smoking prevalence tended to decrease in women born after the 1950s. This is the first report suggesting that the lung cancer epidemic in Dutch women is coming to an end. Although the increase in lung cancer incidence and mortality among Dutch women has been one of the most dramatic in Europe, the recent decrease in young women is expected to be followed by a future leveling off or a slight decrease in overall female lung cancer rates. © 2008 Wiley‐Liss, Inc.