bluuebunny/crossref_metadata_2025 huggingface dataset:
MEK Inhibitor PD0325901 Significantly Reduces the Growth of Papillary Thyroid Carcinoma Cells In vitro and In vivo
Authors: Henderson Ying C. , Chen Yunyun , Frederick Mitchell J. , Lai Stephen Y. , Clayman Gary L.
Published: June 2010

Papillary thyroid carcinomas (PTC) are the most common type of thyroid malignancy. Most PTC carry one of the two mutations, RET/PTC rearrangement or BRAF mutation. Both mutations are able to activate the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase (MEK/ERK) signaling transduction pathway leading to cellular proliferation, differentiation, and apoptosis. PD0325901 is a specific MEK1/2 inhibitor and therefore is a promising drug to treat thyroid cancers with either RET/PTC or BRAF mutation. In this study we tested the effects of PD0325901 on PTC cells harboring either mutation in vitro by growth curves and Western blots and in vivo using a murine orthotopic xenograft model. We found that 50% growth inhibition (GI50) by PD0325901 was 11 nmol/L for the PTC cells with the RET/PTC1 rearrangement and 6.3 nmol/L for PTC cells with a BRAF mutation, with both concentrations readily achievable in serum. After 1 week of oral administration of PD0325901 (20–25 mg/kg/day) in mice, no tumor growth was detected in mice inoculated with PTC cells bearing a BRAF mutation. For PTC with the RET/PTC1 rearrangement, the average tumor volume of the orthotopic tumor was reduced by 58% as compared with controls. In conclusion, our data suggested that PTC cells carrying a BRAF mutation were more sensitive to PD0325901 than were PTC cells carrying the RET/PTC1 rearrangement. Our findings support the clinical evaluation of PD0325901 for patients with PTC and potentially other carcinomas with BRAF mutations. Mol Cancer Ther; 9(7); 1968–76. ©2010 AACR.
Persistent Pulmonary Hypertension of the Newborn Successfully Treated with Beraprost Sodium: A Retrospective Chart Review
Authors: Nakwan Narongsak , Nakwan Narongwit , Wannaro Jeerawan
Published: June 2010

Background: Persistent pulmonary hypertension of the newborn (PPHN) is one of the most serious conditions in neonates resulting in a high mortality and morbidity. New alternative therapies for PPHN have been sought to improve survival and reduce morbidity. Objectives: To report an initial experience of using beraprost sodium (BPS) to treat infants with PPHN and to assess its effect on oxygenation and hemodynamic stability over a 72-hour study period. Methods: The clinical data of neonates who received BPS as an adjunctive therapy for PPHN in our hospital between July 2007 and June 2008 were retrospectively reviewed. Results: During the study period, 7 infants with PPHN were successfully treated with BPS. The mean gestational age and birth weight were 39.3 ± 1.5 weeks and 3,365.7 ± 569.8 g, respectively. BPS was initiated at a median age of 42.7 h after birth (range: 2.1–166.5 h) with a baseline mean oxygen index (OI) of 33.9 ± 15.7 and a baseline mean systolic blood pressure (SBP) of 79.4 ± 9.9 mm Hg. The mean difference of OI at 24, 48 and 72 h following the treatment was –15.7 ± 14.8 (p = 0.043), –18.2 ± 12.3 (p = 0.018) and –16.7 ± 17.5 (p = 0.042), respectively. The mean SBP was significantly reduced as early as 6 h after initiation of treatment (–11.1 ± 11.5 mm Hg, p = 0.034) without changes in heart rate. Three cases were complicated with chronic lung disease, and the remaining 4 cases were normal at hospital discharge. No neurodevelopmental and cardiopulmonary disorders were observed in all cases at 1 year of age. Conclusions: BPS may be used as an alternative treatment for infants with PPHN giving a significant improvement in oxygenation.
Predictive Genetic Tests in Neurodegenerative Disorders: A Methodological Approach Integrating Psychological Counseling for At-Risk Individuals and Referring Clinicians
Authors: Mariotti C. , Ferruta A. , Gellera C. , Nespolo C. , Fancellu R. , Genitrini S. , Di Bella D. , Panzeri M. , Nanetti L. , Tomasello C. , Taroni F. , Foresti G. , Astori S.
Published: June 2010

The identification of the molecular basis of numerous hereditary neurological disorders allowed the feasibility of predictive genetic tests for at-risk family members. In agreement with international guidelines, we tested a protocol for a predictive test to optimize cooperation among specialists, well-being of participants, and organization of clinical activities. The psychiatrist/psychologist did not meet the at-risk subjects, but cooperated with the team, integrating psychological support for participants and clinicians. We enrolled 60 subjects at risk for Huntington disease, and 32 at risk for spinocerebellar ataxias. Seventy-two subjects (78%) continued the visit program; 55 (60%) received the genetic result, and 38 subjects (41%) completed the program. Participation and outcome were similar in both groups. Mean psychological scores were all below significant levels; however, the need for psychological support was recognized for 5 mutation carriers and a non-carrier. Our data provide a methodological example of a simple and safe procedure for a predictive test, and indicate that the clinical conference represents a good setting to handle psychosocial impact associated with disclosure of genetic results in hereditary late-onset disorders.
Land Surface Heating and the North American Monsoon Anticyclone: Model Evaluation from Diurnal to Seasonal
Authors: Kelly Patrick , Mapes Brian
Published: June 2010

Data from several regional and global models (including model-based analysis data) are compared with field data from the North American Monsoon Experiment (NAME), from observational sites as well as satellite retrievals. On the regional scale (NAME tier 1.5), sensible heating is shown to exceed latent and is furthermore concentrated in the lower half of the troposphere, so in considering the North American monsoon (NAM) midlevel anticyclone, the authors focus on radiative and turbulent energy fluxes at the surface. Models exhibit large discrepancies in their simulation of the mean diurnal cycle of these fluxes as well as in their sensitivity of evaporative fraction to recent rainfall. Most of the models examined have too much net radiation due to excessive shortwave surface flux (too little cloud) and too much sensible heating. These high biases in sensible heating appear to drive overpredictions of both the daily and seasonal rise of 500-hPa heights in the NAM anticyclone. This diurnal–seasonal resemblance suggests that calibrating surface heating processes using readily field-observed diurnal variations could lead to improvements in seasonal-time-scale NAM simulations.
Unemployment and Subjective Well-being
Authors: Ervasti Heikki , Venetoklis Takis
Published: June 2010

In this article we focus on the level of subjective well-being and its determinants among the unemployed as compared to those currently in paid labour. We subject three strongly contradictory theoretical approaches to an empirical test. The first is the traditional deprivation theory, which maintains that unemployment is a major psychological stressor. The second is the incentive theory, which claims that the level of well-being among the unemployed may be sufficiently high to discourage them from actively and effectively searching for a new job and re-entering the labour market. The third approach emphasizes the adverse effects of financial stress for subjective well-being during unemployment. We use the European Social Survey (ESS) data from 21 countries in our empirical analysis. We find no support for the incentive theory. The deprivation theory points in the right direction by stressing the psychological factors associated with unemployment but makes a notable omission by disregarding the financial strain which, according to our analysis, proves to be crucial for the well-being of the unemployed.
Edinburgh 2010, Ecumenism, and a Contemporary Challenge to the Roman Catholic Mission Movement
Authors: Whelan Thomas R.
Published: June 2010

The Edinburgh 2010 centennial celebrations offer an opportunity to all churches to urgently review the many implications of ‘mission’ as a ‘theological note of church’ over the past one hundred years. Given that the World Council of Churches indirectly owes its origins and inspiration to ‘Edinburgh 1910’ (and the WCC retains ‘mission’ as a core ecclesial value), it is incumbent on all Christian churches to reflect seriously on the implications of their joint service of the one missio Dei. The Roman Catholic Church, not present at Edinburgh 1910, is now a player in the centennial conference and has much to bring to the table as well as to receive from it. The Irish missionary movement has often been seen as irrelevant to the daily workings of the Catholic Church in Ireland and being merely representative of it: the reciprocity of the mission movement in all its dimensions now becomes one of many important theological questions that need to be addressed.
An Exploratory Study of Corporate Social Responsibility in the U.S. Travel Industry
Authors: Sheldon Pauline J. , Park Sun-Young
Published: June 2010

The travel industry depends heavily on environmental and cultural resources, making responsible business practices essential to achieve sustainable tourism. This study aims to understand the U.S. travel industry’s opinions about and engagement in corporate social responsibility (CSR) by surveying the membership of Travel Industry Association of America (TIA). It examines the most common CSR activities and identifies drivers and inhibitors in achieving CSR. Results show an agreement among TIA members about the importance of CSR for the travel industry, now more than ever. The majority of respondents currently engage in some CSR and 24% have a person dedicated to CSR activities. The main drivers of CSR activities are enhanced reputation, and community-based issues. The main inhibitors are lack of resources and lack of understanding. The results show a predominance of environmental (rather than sociocultural) CSR projects. The findings imply an urgent need for clear conceptualization and directions for CSR engagement by the travel industry.
Hepatic Enzyme Induction
Authors: Maronpot Robert R. , Yoshizawa Katsuhiko , Nyska Abraham , Harada Takanori , Flake Gordon , Mueller Gundi , Singh Bhanu , Ward Jerrold M.
Published: June 2010

Hepatic enzyme induction is generally an adaptive response associated with increases in liver weight, induction of gene expression, and morphological changes in hepatocytes. The additive growth and functional demands that initiated the response to hepatic enzyme induction cover a wide range of stimuli including pregnancy and lactation, hormonal fluctuations, dietary constituents, infections associated with acute-phase proteins, as well as responses to exposure to xenobiotics. Common xenobiotic enzyme inducers trigger pathways involving the constitutive androstane receptor (CAR), the peroxisome proliferator-activated receptor (PPAR), the aryl hydrocarbon receptor (AhR), and the pregnane-X-receptor (PXR). Liver enlargement in response to hepatic enzyme induction is typically associated with hepatocellular hypertrophy and often, transient hepatocyte hyperplasia. The hypertrophy may show a lobular distribution, with the pattern of lobular zonation and severity reflecting species, strain, and sex differences in addition to effects from specific xenobiotics. Toxicity and hepatocarcinogenicity may occur when liver responses exceed adaptive changes or induced enzymes generate toxic metabolites. These undesirable consequences are influenced by the type and dose of xenobiotic and show considerable species differences in susceptibility and severity that need to be understood for assessing the potential effects on human health from similar exposures to specific xenobiotics.
Pleuropulmonary Blastoma in an Equine Fetus
Authors: Woolford L. , Staniek G. , Blunden A. S.
Published: June 2010

Pleuropulmonary blastoma (PPB) is a rare biphasic tumor of children formed by mixed epithelial-and-mesenchymal elements. In this article, the authors report a pulmonary mass in an equine fetus with characteristics of PPB. A soft multicystic broad-based pleural mass was identified in the right caudal lung lobe. The mass comprised solid areas of loose mesenchyme, fenestrated by small ducts or large cystic areas lined by cuboidal epithelium. Mesenchymal elements had moderate anisocytosis, anisokaryosis, and cellular pleomorphism and were immunoreactive for vimentin. Epithelial cells lining ducts and cystic lumina were nonciliated and cuboidal with central round nuclei, minimal cellular pleomorphism, and strong immunoreactivity for cytokeratin. Pertinent characteristics in common with human PPB were the pleural-based location, the dual solid or delicate multiloculated cystic structure, the primitive mesenchymatous stroma fenestrated by well-differentiated cuboidal epithelial-lined lumina, and the occurrence during gestation.
Pathbase and the MPATH Ontology
Authors: Schofield P. N. , Gruenberger M. , Sundberg J. P.
Published: June 2010

Pathbase, the database of mouse histopathology images, was developed as a resource to provide free access to representative images of lesions in background and mutant strains of laboratory mice. When utilized with diagnostic workups or phenotyping of mutant mice, it can provide a “virtual second opinion” for those working without access to groups of experienced pathologists. This is a community resource, and it facilitates the sharing of expertise and data among members of the pathology community worldwide. MPATH—the mouse pathology ontology—was developed alongside Pathbase for the annotation of images and now represents an important resource for the coding of diagnoses, permitting sophisticated data retrieval and computational analysis of mouse phenotypes. In this article, the structure and use of MPATH is discussed, along with current and future challenges for the coding of mutant mouse phenotypes.
Aggression in Sexually Abused Trafficked Girls and Efficacy of Intervention
Authors: Deb Sibnath , Mukherjee Aparna , Mathews Ben
Published: June 2010

The broad objective of this study was to understand the incidence and severity of aggression among sexually abused girls who were trafficked and who were then further used for commercial sexual exploitation (referred to subsequently as sexually abused trafficked girls). In addition, the impact of counseling for minimizing aggression in these girls was investigated. A group of 120 sexually abused trafficked Indian girls and a group of 120 nonsexually abused Indian girls, aged 13 to 18, participated in the study. The sexually abused trafficked girls were purposively selected from four shelters located in and around Kolkata, India. The nonsexually abused girls were selected randomly from four schools situated near the shelters, and these girls were matched by age with the sexually abused trafficked girls. Data were collected using a Background Information Schedule and a standardized psychological test, that is, The Aggression Scale. Results revealed that 16.7% of the girls were first sexually abused between 6 and 9 years of age, 37.5% between 10 and 13 years of age, and 45.8% between 14 and 17 years of age. Findings further revealed that 4.2% of the sexually abused trafficked girls demonstrated saturated aggression, and 26.7% were highly aggressive, that is, extremely frustrated and rebellious. Across age groups, the sexually abused trafficked girls suffered from more aggression ( p < .05), compared with the nonvictimized girls. Psychological interventions, such as individual and group counseling, were found to have a positive impact on the sexually abused trafficked girls. These findings should motivate counselors to deal with sexually abused children. It is also hoped that authorities in welfare homes will understand the importance of counseling for sexually abused trafficked children, and will appoint more counselors for this purpose.
Intimate Partner Violence Within Law Enforcement Families
Authors: Anderson Anita S. , Lo Celia C.
Published: June 2010

Using data from the Baltimore Police Stress and Domestic Violence study, the authors examined how exposure to stressful events on the job affects law enforcement employees’ physical aggression toward domestic partners, evaluating the role of negative emotions and authoritarian spillover in mediating the impact of such task-related stress. The authors consulted general strain theory and angry aggression theory to explain domestic violence in police families. Significant positive effects on physical aggression toward an intimate partner were found for variables measuring authoritarian spillover and negative emotions. However, these effects were different for different gender and racial groups.
A Measure of Severe Psychological Abuse Normed on a Nationally Representative Sample of Adults
Authors: Follingstad Diane R.
Published: June 2010

A psychological abuse scale representing truly egregious psychological actions that could occur between adult intimate partners was constructed. To insure that the component behaviors would be viewed as highly problematic, the likely malignant intent of the actions was included in item descriptions. Fourteen categories of psychological abuse were devised as relatively independent forms of destructive behaviors, and, within each category, 3 items were devised to represent increasingly severe psychological actions. A nationally representative sample of adults ( N = 614) responding to an online survey rated the perceived severity of the 42 aversive behaviors. Reliability and validity indicators, along with descriptive data, are presented. The ratings of the sample basically established the items as egregious in nature, the categories as distinct from each other, and the items within categories as varying in expected directions in terms of severity. Except for gender, demographics had little effect on participants’ ratings. Social desirability and dimensions of attachment showed weak relationships with participants’ ratings.
Sleep Loss and Partner Violence Victimization
Authors: Walker Robert , Shannon Lisa , Logan T.K.
Published: June 2010

Intimate partner violence victimization has been associated with serious health problems among women, including many disorders that involve sleep disturbances. However, there has been only limited examination of sleep duration among women with victimization experiences. A total of 756 women with a domestic violence order (DVO) against a male intimate partner were interviewed about their health, mental health, substance use, and partner violence victimization. Face-to-face interviews were conducted from February 2001 to November 2003 for data collection in three rural and one urban county representing different jurisdictional settings. Because the current analyses focused on understanding intimate partner victimization in the past year and associations with sleep disturbance, 147 participants were excluded for reporting a relationship with the DVO partner for less than 6 months in the past year. The final sample for this article was 609. The women reported an average of a little above 5.5 hours of sleep per night. For women in the current study, significant predictors of sleep disturbance included race, number of children, number of other symptoms of depression in the past 2 weeks excluding sleep criteria, number of other symptoms of PTSD in the past 2 weeks excluding sleep criteria, number of chronic physical health problems, and severity of physical violence by the DVO partner in the past year. Addressing short sleep duration among partner victims in health care settings might enhance safety planning and prevent the development of health/mental health problems that can arise from victimization.
Can Norm Theory Explain the Effects of Victim Age and Level of Physical Maturity on Perceptions of Child Sexual Abuse?
Authors: Rogers Paul , Davies Michelle , Anderson Irina , Potton Anita
Published: June 2010

The present study examines the effects of victim age, victim physical maturity, and respondent gender on attributions toward victims, perpetrator, and the nonoffending members of the victim’s family in a hypothetical child sexual abuse (CSA) case. Participants read a brief CSA vignette in which the male perpetrator (a school caretaker) sexually abuses a student in the school changing rooms. The victim was depicted as either a 12- or 15-year-old girl who, in terms of physical maturity, was either pre- or postpubescent. Separate 2 × 2 × 2 ANOVAs were performed on the dependent variables. Results conformed broadly to the study’s predictions with younger victims being viewed more negatively than older victims and the victim’s physical appearance being viewed as more encouraging of CSA for the younger than for the older girl. Female participants were more likely to endorse the belief that the younger victim should have fought back and that the prepubescent 15-year-old victim should have fought back more than her postpubescent counterpart. While attributions toward the perpetrator and victim’s family did not differ across conditions for women, men tended to blame the perpetrator more when victims were younger and the family more when victims were less physically mature. Findings are discussed in relation to norm theory principles, just world theory, and the defensive attribution hypothesis.
Childhood Sexual Abuse Associated With Dating Partner Violence and Suicidal Ideation in a Representative Household Sample in Hong Kong
Authors: Ko Ling Chan  , Yan Elsie , Brownridge Douglas A. , Tiwari Agnes , Fong Daniel Y. T.
Published: June 2010

This study investigated the prevalence and impact of childhood sexual abuse (CSA) on future intimate partner violence (IPV) in dating relationship in Hong Kong, China. A total of 1,154 Chinese adult respondents engaged in dating relationships were interviewed face-to-face about their CSA histories, childhood witnessing of parental violence, adult sexual victimization (ASV) by others and IPV victimization with their current dating partner. Self-reports also measured levels of suicidal ideation, self-esteem, and demographic details. Overall, 1.7% reported some form of CSA with a higher percentage being women. No gender differences were found in the prevalence of either ASV or IPV. Results showed that CSA had an independent effect on physical IPV and suicidal ideation. The odds of IPV were increased by behavioral and psychological factors of victims such as alcohol and drug abuse, sex with partner, and low self-esteem. The odds of suicidal ideation were also increased by drug abuse, childhood witnessing of parental psychological aggression, and low self-esteem. Clinical implications of results included screening for CSA victims and suicidal victims when treating IPV patients, tailoring treatment according to individual IPV victim’s problems, correcting behaviors that are associated with risks of IPV, such as engagement in casual sex and substance abuse, and focusing not only on tangible services but also on the social and psychological aspects that are placing the victims at risk for IPV.
Effect of interfacial microstructure on lap shear strength of friction stir spot weld of aluminium alloy to magnesium alloy
Authors: Sato Y. S. , Shiota A. , Kokawa H. , Okamoto K. , Yang Q. , Kim C.
Published: June 2010

In the present study, an attempt was made to join two dissimilar light metal alloys which are becoming increasingly familiar in the automotive industry, i.e. AA5083 aluminium alloy and AZ31 magnesium alloy, by the friction stir spot welding process. Lap welds were produced with various welding parameters, and interfacial microstructures and lap shear strengths of these welds were examined. Friction stir spot welding produced defect-free welds, even though a thick interfacial layer composed mainly of intermetallic compounds was present. The thickness of the interfacial layer did not appear to affect the lap shear strength of the weld, whereas the distribution of intermetallic compounds in the interfacial layer did so. Microstructural factors of the interface governing the lap shear strength of the weld were examined.
Positional dependence of material flow in friction stir welding: Analysis of joint line remnant and its relevance to dissimilar metal welding
Authors: Kumar K. , Kailas S. V.
Published: June 2010

Understanding material flow in friction stir welding is important for production of sound dissimilar metal welding that control the intermixing of two alloys being welded and consequent formation of new constituents which influences the weld properties. In the present experimental investigation material flow patterns are visualised using dissimilar and similar aluminium alloys using a simple innovative experiment. The experimental results reveal that only a portion of material transported from the leading edge undergoes chaotic flow and the remaining is deposited systematically in the trailing edge of the weld. Using this information it is shown that the formation of a friction stir welding defect, joint line remnant, does not occur only when the weld interface is on the advancing side. The material flow visualisation study has been utilised to analyse the mechanism of weld formation and its usefulness in improving fatigue properties and for dissimilar metal welds.
Effect of fixed location variation in friction stir welding of steels with different carbon contents
Authors: Choi D.-H. , Lee C.-Y. , Ahn B.-W. , Yeon Y.-M. , Park S.-H. C. , Sato Y.-S. , Kokawa H. , Jung S.-B.
Published: June 2010

Dissimilar friction stir welding between steels with different carbon contents was carried out by placing the parent materials at two different fixed locations: the advancing side (AS) and the retreating side (RS). The phase transformation and the depth and width of the weld were affected by the fixed location. A smaller weld nugget was formed, and more martensite transformation occurred when the stronger SK5 steel was fixed at AS, compared to that at RS. This variation was attributed to the difference of temperature and materials flow between AS and RS.
Spot joining of AA 5754 and high strength steel sheets by consumable bit
Authors: Miles M. P. , Feng Z. , Kohkonen K. , Weickum B. , Steel R. , Lev L.
Published: June 2010

Spot joining of dissimilar metal alloys is difficult because of differences in melting temperature as well as differences in composition. If a fusion welding process like resistance spot welding is employed, then alloys mix in the fusion zone and can create brittle intermetallic compounds during solidification. When self-piercing riveting (SPR) is used, the alloys to be joined must be ductile enough to be formed around the rivet. In this paper, a new approach to joining dissimilar metal alloys has been studied, where a consumable bit has been used to create a spot joint between dissimilar alloys. The resulting joint has both metallurgical and mechanical bonding characteristics and can be made between very soft and very hard alloys, like dual phase (DP) 590 and DP 980 and light metals like AA 5754. Lap shear strengths of joints made by friction bit joining (FBJ) are similar to or better than comparable joints made by self-piercing riveting.
Friction stir welding of dissimilar alloys – a perspective
Authors: DebRoy T. , Bhadeshia H. K. D. H.
Published: June 2010

Friction stir welding does not involve bulk melting of the components that are joined. This has inspired attempts to exploit it for joining materials which differ in properties, chemical composition or structure, and where fusion can lead to detrimental reactions. The purpose of this special issue of Science and Technology of Welding and Joining was to assess the status of friction stir welding of dissimilar alloys and to identify the opportunities and challenges for the future.
Drug-dependent clearance of human platelets in the NOD/scid mouse by antibodies from patients with drug-induced immune thrombocytopenia
Authors: Bougie Daniel W. , Nayak Dhirendra , Boylan Brian , Newman Peter J. , Aster Richard H.
Published: June 2010

Drug-induced immune thrombocytopenia (DITP) is a relatively common and sometimes life-threatening condition caused by antibodies that bind avidly to platelets only when drug is present. How drug-dependent antibodies (DDAbs) are induced and how drugs promote their interaction with platelets are poorly understood, and methods for detecting DDAbs are suboptimal. A small animal model of DITP could provide a new tool for addressing these and other questions concerning pathogenesis and diagnosis. We examined whether the nonobese diabetic/severe combined immunodeficient (NOD/scid) mouse, which lacks xenoantibodies and therefore allows infused human platelets to circulate, can be used to study drug-dependent clearance of platelets by DDAbs in vivo. In this report, we show that the NOD/scid model is suitable for this purpose and describe studies to optimize its sensitivity for drug-dependent human antibody detection. We further show that the mouse can produce metabolites of acetaminophen and naproxen for which certain drug-dependent antibodies are specific in quantities sufficient to enable these antibodies to cause platelet destruction. The findings indicate that the NOD/scid mouse can provide a unique tool for studying DITP pathogenesis and may be particularly valuable for identifying metabolite-specific antibodies capable of causing immune thrombocytopenia or hemolytic anemia.
Resistin enhances the expansion of regulatory T cells through modulation of dendritic cells
Authors: Son Young Min , Ahn Sung Min , Kim Gi Rak , Moon Yang Soo , Kim Sang Hoon , Park Yeong-Min , Lee Woon Kyu , Min Tae Sun , Han Seung Hyun , Yun Cheol-Heui
Published: June 2010

Background

Resistin, a member of adipokine family, is known to be involved in the modulation of immune responses including inflammatory activity. Interestingly, resistin is secreted by adipocytes in mice and rats whereas it is secreted by leukocytes in humans. However, the mechanism behind the effect of resistin on the expansion of regulatory T cells (Tregs) remains poorly understood. Therefore, we examined regulatory effect of resistin on the induction and cellular modification of Tregs.

Results

Both protein and mRNA expression of FoxP3, a representative marker of Tregs, increased in a dose-dependent manner when peripheral blood mononuclear cells were treated with resistin. At the same time, resistin had no direct effect on the induction of FoxP3 in CD4+ T cells, suggesting an indirect role through other cells type(s). Since DCs are an important player in the differentiation of T cells, we focused on the role of DCs in the modulation of Tregs by resistin. Resistin suppressed the expression of interferon regulatory factor (IRF)-1 and its target cytokines, IL-6, IL-23p19 and IL-12p40, in DCs. Furthermore, FoxP3 expression is increased in CD4+ T cells when co-cultured with DCs and concomitantly treated with resistin.

Conclusion

Our results suggest that resistin induces expansion of functional Tregs only when co-cultured with DCs.
Association study of genetic variants in eight genes/loci with type 2 diabetes in a Han Chinese population
Authors: Lin Ying , Li Pengqiu , Cai Li , Zhang Ben , Tang Xin , Zhang Xuejun , Li Ying , Xian Yang , Yang Yang , Wang Li , Lu Fang , Liu Xiaoqi , Rao Shaoqin , Chen Ming , Ma Shi , Shi Yi , Bao Mingjing , Wu Jichuan , Yang Yan , Yang Jiyun , Yang Zhenglin
Published: June 2010

Background

At least twenty genes/loci were shown to be associated with type 2diabetes in European original populations. Five of these genes were shown to be associated with type 2 diabetes (T2D) in Chinese populations. The purpose of this study was to replicate the association of genetic vairants in the eight diabetes-related genes/loci with type 2 diabetes in a Han Chinese cohort from western part of China. Nineteen single nucleotide polymorphisms (SNPs) from the eight genes/loci including TCF7L2, HHEX, CDKAL1, SLC30A8, PPARG, IGF2BP2, KCNJ11, and CDKN2A/CDKN2B were genotyped in 1,529 cases and 1,439 controls in a Han Chinese population using the ABI SNaPshot method. The meta-analysis of the association between rs7903146 in TCF7L2 gene and T2D in the Han Chinese was performed.

Results

Among the eight genes/loci examined, we found that four were significantly associated with T2D. Although previous studies showed that the association between the SNP rs7903146 in the TCF7L2 gene and T2D was controversial within the Han Chinese population, we have confirmed the significant association between the SNP rs7903146 in the TCF7L2 gene and T2D in both this study and the meta-analysis in the population. In addition, we also confirmed that three SNPs (rs1111875, rs7923837 and rs5015480) in HHEX , one SNP (rs10946398) in CDKAL1, and three SNPs (rs13266634, rs3802177 and rs11558471) in SLC30A8 were significantly associated with T2D in the population being studied.

Conclusions

We demonstrated that the variants in TCF7L2, CDKAL1, HHEX, and SLC30A8 genes are associated with T2D in a Han Chinese population.
Fibromuscular dysplasia presenting as a renal infarction: a case report
Authors: Van den Driessche Annelies , Van Hul Erik , Ichiche Malika , Verpooten Gert A , Bosmans Jean-Louis
Published: June 2010

Introduction

Fibromuscular dysplasia is a non-atherosclerotic, non-inflammatory disease that most commonly affects the renal and internal carotid arteries.

Case presentation

We present the case of a 44-year-old Caucasian man who was admitted with complaints of loin pain and hypertension. A computed tomography scan of the abdomen revealed a right renal infarction with a nodular aspect of the right renal artery. Subsequent renal angiography revealed a typical 'string of beads' pattern of the right renal artery with thrombus formation. Oral anticoagulation was started and the secondary hypertension was easily controlled with anti-hypertensive drugs. At follow-up, our patient refused percutaneous transluminal renal angioplasty as a definitive treatment.

Conclusions

Fibromuscular dysplasia is the most common cause of renovascular hypertension in patients under 50 years of age. Presentation with renal infarction is rare.

In fibromuscular dysplasia, angioplasty has been proven to have, at least for some indications, an advantage over anti-hypertensive drugs. Therefore, hypertension secondary to fibromuscular dysplasia is the most common cause of curable hypertension.
Pivotal Advance: Tumor-mediated induction of myeloid-derived suppressor cells and M2-polarized macrophages by altering intracellular PGE2 catabolism in myeloid cells
Authors: Eruslanov Evgeniy , Daurkin Irina , Ortiz Javier , Vieweg Johannes , Kusmartsev Sergei
Published: June 2010

Tumors impair function of tumor-infiltrated antigen-presenting cells by altering intracellular PGE2 catabolism in the myeloid cells.

Recent studies suggest that tumor-infiltrated myeloid cells frequently up-regulate COX-2 expression and have enhanced PGE2 metabolism. This may affect the maturation and immune function of tumor-infiltrated antigen-presenting cells. In vitro studies demonstrate that tumor-derived factors can skew GM-CSF-driven differentiation of Th1-oriented myeloid APCs into M2-oriented Ly6C+F4/80+ MDSCs or Ly6C–F4/80+ arginase-expressing macrophages. These changes enable myeloid cells to produce substantial amounts of IL-10, VEGF, and MIP-2. The tumor-mediated inhibition of APC differentiation was associated with the up-regulated expression of PGE2-forming enzymes COX-2, mPGES1 in myeloid cells, and the simultaneous repression of PGE2-catabolizing enzyme 15-PGDH. The presence of tumor-derived factors also led to a reduced expression of PGT but promoted the up-regulation of MRP4, which works as a PGE2 efflux receptor. Addition of COX-2 inhibitor to the BM cell cultures could prevent the tumor-induced skewing of myeloid cell differentiation, partially restoring cell phenotype and down-regulating the arginase expression in the myeloid APCs. Our study suggests that tumors impair the intracellular PGE2 catabolism in myeloid cells through simultaneous stimulation of PGE2-forming enzymes and inhibition of PGE2-degrading systems. This tumor-induced dichotomy drives the development of M2-oriented, arginase-expressing macrophages or the MDSC, which can be seen frequently among tumor-infiltrated myeloid cells.
Postcards, green cards and telephone calls: therapeutic contact with individuals following self-harm
Authors: Kapur Navneet , Cooper Jayne , Bennewith Olive , Gunnell David , Hawton Keith
Published: June 2010

Self-harm is a major public health problem and universal interventions such as contacting individuals by post or telephone following a self-harm episode have received much attention recently. They may also appeal to service providers because of their low cost. However, a widespread introduction of these interventions cannot be justified without a better understanding of whether they work, and if so how.
MRCPsych courses: the national picture
Authors: Berrisford Giles S. , Vassilas Christopher A.
Published: June 2010

Aims and method

MRCPsych courses are a mandatory part of training for psychiatric trainees, yet relatively little is known about them. A questionnaire was devised and sent to all course organisers in the UK.

Results

Thirty courses were identified. There was large variation in nearly all areas of content and delivery of courses, including cost, number of hours of teaching, size of course and organisation. Implementation of the College requirements in terms of service user and carer involvement was patchy.

Clinical implications

These courses are costly in terms of both time and money, and individuals involved in psychiatric training must be able to demonstrate that they are of a high quality and have been properly evaluated. Suggestions to improve the running of these courses include: the exchange of information among the different courses; a database of courses; and some uniformity in the appointment of those in charge of the course.
Charged residues in the C-terminus of the P2Y1 receptor constitute a basolateral-sorting signal
Authors: Wolff Samuel C. , Qi Ai-Dong , Harden T. Kendall , Nicholas Robert A.
Published: June 2010

The P2Y1 receptor is localized to the basolateral membrane of polarized Madin-Darby canine kidney (MDCK) cells. In the present study, we identified a 25-residue region within the C-terminal tail (C-tail) of the P2Y1 receptor that directs basolateral sorting. Deletion of this sorting signal caused redirection of the receptor to the apical membrane, indicating that the region from the N-terminus to transmembrane domain 7 (TM7) contains an apical-sorting signal that is overridden by a dominant basolateral signal in the C-tail. Location of the signal relative to TM7 is crucial, because increasing its distance from the end of TM7 resulted in loss of basolateral sorting. The basolateral-sorting signal does not use any previously established basolateral-sorting motifs, i.e. tyrosine-containing or di-hydrophobic motifs, for function, and it is functional even when inverted or when its amino acids are scrambled, indicating that the signal is sequence independent. Mutagenesis of different classes of amino acids within the signal identified charged residues (five basic and four acidic amino acids in 25 residues) as crucial determinants for sorting function, with amidated amino acids having a lesser role. Mutational analyses revealed that whereas charge balance (+1 overall) of the signal is unimportant, the total number of charged residues (nine), either positive or negative, is crucial for basolateral targeting. These data define a new class of targeting signal that relies on total charge and might provide a common mechanism for polarized trafficking of epithelial proteins.
Synthesis and Thermally Stable Helix-Dimer Formation of Amidohelicene Oligomers
Authors: Amemiya Ryo , Ichinose Wataru , Yamaguchi Masahiko
Published: June 2010

Optically active amidohelicene monomer to nonamer were synthesized in high yields by a two-directional method. The CD spectra in chloroform exhibited a large difference between dimer and the higher homologs, and vapor pressure osmometry studies revealed the formation of dimeric aggregates for the latter. It is noted that amidohelicene oligomers possessing two-atom linking groups between helicene and m-phenylene spacer formed helix-dimers in solution as were ethynylhelicene oligomers. The helix-dimer of the amidohelicene octamer in chloroform was very stable, and did not dissociate at 5 × 10−8 M on heating to 60 °C. The dissociation of the amidohelicene oligomers to random-coil state took place in hydrogen-bonding breaking solvents, DMSO or THF. The equilibrium between helix-dimer and random-coil changed by varying the ratio in the mixed solvents of chloroform and DMSO. Notably, the equilibriums were not affected by temperature for various mixtures of helix-dimer and random-coil. Thus, the sensitivity toward the environment was quite different between the amido- and ethynylhelicene oligomers.
Synthesis of 2-Halogenated Quinolines by Halide-Mediated Intramolecular Cyclization of o-Alkynylaryl Isocyanides
Authors: Mitamura Takenori , Nomoto Akihiro , Sonoda Motohiro , Ogawa Akiya
Published: June 2010

When o-alkynylaryl isocyanides 1 are treated with triethylamine in chloroform, intramolecular chlorinating cyclization of the isocyanides takes place, affording the corresponding 2-chlorinated quinoline derivatives 2 in good to excellent yields, selectively. Bromoform can be also used for the brominating cyclization of 1. Furthermore, fluorinating and iodinating cyclization of o-alkynylaryl isocyanides has been attained by the selection of fluoride and iodide (ion) sources.
Plasma free fatty acid reference interval in South African neonates in the first week of life
Authors: Omar F , van der Watt G , November V , Pillay T S
Published: June 2010

Background

Non-esterified fatty acid (NEFA) levels are an important diagnostic tool in the investigation of neonatal hypoglycaemia. NEFA reference intervals have not been reported for neonates previously.

Methods

The objective of this study was to determine an NEFA reference interval for neonates.

Results

Heparinized plasma obtained from 106 healthy neonates in the first week of life was analysed using the Roche “Free fatty acid, Half-micro test” kit. Results were then analysed statistically for normality (Shapiro–Wilk test) and reference interval determined non-parametrically (bootstrap method).

Conclusions

NEFA levels displayed a non-Gaussian distribution and the reference interval (2.5th and 97.5th percentiles) was 0.2–1.5 mmol/L (90% confidence intervals 0.1–0.3 and 1.4–2.0 mmol/L, respectively). The NEFA reference interval in South African neonates less than a week old is similar to that described in infants (1–12 months), indicating that this reference range can be used over the entire neonatal period.
Arginine methylation in subunits of mammalian pre-mRNA cleavage factor I
Authors: Martin Georges , Ostareck-Lederer Antje , Chari Ashwin , Neuenkirchen Nils , Dettwiler Sabine , Blank Diana , Rüegsegger Ursula , Fischer Utz , Keller Walter
Published: June 2010

Mammalian cleavage factor I (CF Im) is composed of two polypeptides of 25 kDa and either a 59 or 68 kDa subunit (CF Im25, CF Im59, CF Im68). It is part of the cleavage and polyadenylation complex responsible for processing the 3′ ends of messenger RNA precursors. To investigate post-translational modifications in factors of the 3′ processing complex, we systematically searched for enzymes that modify arginines by the addition of methyl groups. Protein arginine methyltransferases (PRMTs) are such enzymes that transfer methyl groups from S-adenosyl methionine to arginine residues within polypeptide chains resulting in mono- or dimethylated arginines. We found that CF Im68 and the nuclear poly(A) binding protein 1 (PABPN1) were methylated by HeLa cell extracts in vitro. By fractionation of these extracts followed by mass spectral analysis, we could demonstrate that the catalytic subunit PRMT5, together with its cofactor WD45, could symmetrically dimethylate CF Im68, whereas pICln, the third polypeptide of the complex, was stimulatory. As sites of methylation in CF Im68 we could exclusively identify arginines in a GGRGRGRF or “GAR” motif that is conserved in vertebrates. Further in vitro assays revealed a second methyltransferase, PRMT1, which modifies CF Im68 by asymmetric dimethylation of the GAR motif and also weakly methylates the C-termini of both CF Im59 and CF Im68. The results suggest that native—as compared with recombinant—protein substrates may contain additional determinants for methylation by specific PRMTs. A possible involvement of CF Im methylation in the context of RNA export is discussed.
The ‘Retro-Fibular Wire’
Authors: Loughenbury P. R. , Harwood P. J. , Tunstall R. , Britten S.
Published: June 2010

Anatomical atlases document safe corridors for placement of wires when using fine-wire circular external fixation. The furthest posterolateral corridor described in the distal tibia is through the fibula. This limits the crossing angle and stability of the frame. In this paper we describe a new, safe Retro-Fibular Wire corridor, which provides greater crossing angles and increased stability. In a cadaver study, 20 formalin-treated legs were divided into two groups. Wires were inserted into the distal quarter of the tibia using two possible corridors and standard techniques of dissection identified the distance of the wires from neurovascular structures.

In both groups the posterior tibial neurovascular bundle was avoided. In group A the peroneal artery was at risk. In group B this injury was avoided. Comparison of the groups showed a significant difference (p < 0.001).

We recommend the Retro-Fibular wire technique whereby wires are inserted into the tibia mid-way between the posteromedial border of the fibula and the tendo Achillis, at 30° to 45° to the sagittal plane, and introduced from a posterolateral to an anteromedial position. Subsequently, when using this technique in 30 patients, we have had no neurovascular complications or problems relating to tethering of the peroneal tendons.
The lateral approach to intraspinal reimplantation of the brachial plexus
Authors: Camp S. J. , Carlstedt T. , Casey A. T. H.
Published: June 2010

Intraspinal re-implantation after traumatic avulsion of the brachial plexus is a relatively new technique. Three different approaches to the spinal cord have been described to date, namely the posterior scapular, anterolateral interscalenic multilevel oblique corpectomy and the pure lateral. We describe an anatomical study of the pure lateral approach, based on our clinical experience and studies on cadavers.
The "Art" of Politics
Authors: Lapatin Kenneth
Published: June 2010

Appreciation of so-called "works of art" in antiquity was based on more than art-historical factors. Many were potent symbols of civic, religious, and cultural identity. Thus their movements rarely went unnoticed. Greek and Latin authors record over 50 examples of the restitution of previously confiscated artifacts, including some of the most famous artworks of classical antiquity. These were returned to their original owners for diverse reasons—including political calculation, religious piety, popular outcry, and, apparently, the economics of tourism—providing an alternative lens through which to interrogate the prevailing aesthetic frameworks of ancient and modern art histories.
Introduction: The Art of Art History in Greco-Roman Antiquity
Authors: Squire Michael
Published: June 2010

To what extent can we talk about Greco-Roman processes of making, viewing, and writing about images as "art history"? How did ancient concepts of image-making resemble those used in other cultural spheres? What role do post-Enlightenment systems of aesthetics continue to play within the study of (what some prefer to call) ancient "visual culture"? The introduction to this guest-edited volume explains why these questions are so pressing. Concepts of "art" have long shaped the study of "classical art history" in the past. But debates about the historicism or essentialism of "art" must also determine the future of the discipline and its place within "classics," "archaeology," and "art history" at large.