bluuebunny/crossref_metadata_2025 huggingface dataset:
Pathological yawning in a patient with anxiety and chronic disease anaemia
Authors: Taskapilioglu O , Akkaya C , Sarandol A , Kirli S
Published: May 2008

Abstract

Yawning, frequent in daily life, is accepted as a complex arousal reflex. Excessive yawning may be due to neurological, psychiatric, infectious, gastrointestinal or metabolic diseases. This reflex has also been associated with different selective serotonin reuptake inhibitors. We report a female patient, with excessive yawning, who was on selective serotonin reuptake inhibitor treatment with the diagnosis of generalised anxiety disorder. She was then found to have endometrial carcinoma. Her complaints of palpitation, shortness of breath and loss of energy might be explained by a psychiatric disease and/or anaemia. Previous anaemic periods and partial response of her psychiatric symptoms during last 3 years alerted us to think about an organic cause. Investigations for chronic disease anaemia resulted in diagnosis of endometrial carcinoma. This case is a good example showing misdiagnosis caused by medical stigmatisation.
Consequences of chronic social stress on behaviour and vasopressin gene expression in the PVN of DBA/2OlaHsd mice—influence of treatment with the CRHR1-antagonist R121919/NBI 30775
Authors: Erhardt A. , Müller MB , Rödel A. , Welt T. , Ohl F. , Holsboer F. , Keck ME
Published: May 2008

Accumulating evidence suggests that corticotropin-releasing hormone (CRH) neurocircuitry modulate the neuroendocrine and behavioural phenotypes in depression and anxiety. Thus, the administration of the selective CRH-receptor 1 (CRHR1)—antagonist R121919/NBI 30775 has proven its ability to act as an anxiolytic in rats. It is still unclear whether vasopressinergic neuronal circuits, which are known to be involved in the regulation of emotionality, are affected by R121919/NBI 30775. Using DBA/2OlaHsd mice, we investigated the effects of chronic social defeat and concomitant treatment with R121919/NBI 30775 on 1) the behavioural profile in the modified hole board test and 2) in-situ hybridization analysis—based expression of arginine vasopressin (AVP) and CRH mRNA in both the hypothalamic paraventricular nucleus and supraoptic nucleus. The results suggest that chronic social defeat leads to increased avoidance behaviour and reduction in directed exploration, general exploration, and locomotion. Chronic treatment with the CRHR1-antagonist was effective in reversing the directed exploration to control level. The dissection of the antagonist-treated group into responders and non-responders using the parameter time spent on board revealed further positive effects of R121919/NBI 30775 on avoidance behaviour and locomotion. Behavioural changes were accompanied by alterations in AVP gene expression in the paraventricular nucleus. Taken together, the anxiolytic action of the CRHR1 antagonist was found in a subgroup of animals only, and further studies have to be done to clarify the inter-individual biological differences in response patterns to this compound to optimise its application under clinical conditions.
Evidence for selective executive function deficits in ecstasy/polydrug users
Authors: Fisk JE , Montgomery C.
Published: May 2008

Previous research has suggested that the separate aspects of executive functioning are differentially affected by ecstasy use. Although the inhibition process appears to be unaffected by ecstasy use, it is unclear whether this is true of heavy users under conditions of high demand. Tasks loading on the updating process have been shown to be adversely affected by ecstasy use. However, it remains unclear whether the deficits observed reflect the executive aspects of the tasks or whether they are domain general in nature affecting both verbal and visuo-spatial updating. Fourteen heavy ecstasy users (mean total lifetime use 1000 tablets), 39 light ecstasy users (mean total lifetime use 150 tablets) and 28 non-users were tested on tasks loading on the inhibition executive process (random letter generation) and the updating component process (letter updating, visuo-spatial updating and computation span). Heavy users were not impaired in random letter generation even under conditions designed to be more demanding. Ecstasy-related deficits were observed on all updating measures and were statistically significant for two of the three measures. Following controls for various aspects of cannabis use, statistically significant ecstasy-related deficits were obtained on all three updating measures. It was concluded that the inhibition process is unaffected by ecstasy use even among heavy users. By way of contrast, the updating process appears to be impaired in ecstasy users with the deficit apparently domain general in nature.
Topiramate add-on treatment in schizophrenia: a randomised, double-blind, placebo-controlled clinical trial
Authors: Afshar H , Roohafza H , Mousavi G , Golchin S , Toghianifar N , Sadeghi M , Talaei M
Published: May 2008

Abstract

Glutamate antagonists such as topiramate have been proposed based on the glutamate hypothesis of schizophrenia because its properties encourage its exploration and possible development as a medication for the treatment of schizophrenia. A randomised, double-blind, placebo-controlled clinical trial was performed on 18- to 45-year-old patients with schizophrenia. Baseline information including vital signs, height, weight, smoking status, demographic characteristics, (past) psychiatric history, medication history and medication-related adverse effects were collected. Patients were randomly assigned to a topiramate or placebo group. Efficacy of medication was measured by administering Positive and Negative Syndrome Scale (PANSS), and tolerability of treatment was recorded on day 0 (baseline), day 28 and day 56. PANSS values (95% confidence interval) at baseline, day 28 and day 56 in the topiramate group were 96.87 (85.37–108.37), 85.68 (74.67–96.70) and 76.87 (66.06–87.69), respectively; compared with 101.87 (90.37–113.37), 100.31 (89.29–111.32) and 100.56 (89.74–111.37) in the placebo group. General linear model for repeated measures analysis showed that topiramate has lowered PANSS values significantly compared with the placebo group. Similar significant decline patterns were found in all three subscales (negative, positive and psychopathology sign). Clinical response (more than 20% reduction in PANSS) was significantly higher in topiramate-treated subjects than controls (50% vs 12.5%). Topiramate can be an effective medication in controlling schizophrenic symptoms, considering its effect on negative symptoms and controlling antipsychotic-associated weight gain.
Effect of distigmine bromide on the central cholinergic system
Authors: Nakayama K , Katsu H , Kitazumi K
Published: May 2008

Abstract

Distigmine bromide (3, 3’-[hexamethylenebis (methyliminocarbonyloxy)] bis (1-methylpyridinium) dibromide), an acetylcholinesterase (AChE) inhibitor, produced a time-dependent and dose-dependent increase in acetylcholine (ACh) levels in the medial prefrontal cortex of rats. The overt cholinergic behaviours, such as tremor, fasciculation and lacrimation, were also elicited by distigmine bromide. The onset and duration of these behaviours were reflected in the microdialysis data showing that distigmine bromide enhances cholinergic neurotransmission in rat brain. The dose of distigmine bromide eliciting increase in ACh in the medial prefrontal cortex of rats correlated well with its dose for the induction of the cholinergic behaviours. Furthermore, distigmine bromide was an equipotent inhibitor of AChE and butyrylcholinesterase (BuChE) activities in the present study. From these findings, it is suggested that distigmine bromide may produce centrally mediated behavioural signs by increasing the ACh levels in the brain, resulting from its AChE and BuChE inhibitions.
Clozapine: more than 900 mg/day may be needed
Authors: MacCall C , Billcliff N , Igbrude W , Natynczuk S , Spencer EP , Flanagan RJ
Published: May 2008

Abstract

Patients may fail to respond to clozapine treatment despite use of the maximum licensed UK dosage (900 mg/day) because of ultra-rapid metabolism of the drug. We present the findings of a study of a national clozapine/norclozapine assay service for the period 1997–2005 and three individual case studies of patients treated with clozapine in doses greater than 900 mg/day. Clinicians should be alert to the possibility of treatment failure because of rapid clozapine clearance secondary to genetic factors and heavy cigarette consumption. This may necessitate the use of clozapine in doses up to 1400 mg/day, notably in young male smokers. Doses of greater than 900 mg/day are rarely justified in women. Anyone given relatively high-dose clozapine (600 mg/day or more) should be monitored regularly for adverse events and changes in smoking habit.
Effects of Rhodiola rosea L. extract on behavioural and physiological alterations induced by chronic mild stress in female rats
Authors: Mattioli L , Funari C , Perfumi M
Published: May 2008

Abstract

Rhodiola rosea L. is one of the most popular adaptogen and an antistress plant in European and Asiatic traditional medicine. Our previous studies have confirmed the adaptogenic and antistress properties of a single administration of R. rosea L. extract in rats exposed to acute stress. There is increasing evidence that prolonged exposure to stressful life events and depression are both related to significant behavioural, endocrinological and neurobiological changes in human and animal subjects. The aim of this study was to determine whether chronic treatment with a hydroalcoholic R. rosea extract (RHO) standardized in 3% rosavin and 1% salidroside can prevent alterations induced in female rats following 6 weeks of a chronic mild stress (CMS) procedure. This was analysed through the behavioural and physiological parameters of consumption of 1% sucrose solution, locomotor and exploratory activities, body weight gain and oestrous cycle length. After the first 3 weeks of stress, RHO was administered daily by gavage at doses of 10, 15 and 20 mg/kg for the remaining 3 weeks. In addition, the antidepressant drug fluoxetine (10 mg/kg os), which has been shown to reverse CMS-induced disruptions, was used as the reference treatment. Rats subjected to the CMS procedure demonstrated decreased sucrose intake, reduced moving behaviour, minimized weight gain and dysregulation of their oestrous cycle. Treatment with RHO completely reverted all of these changes. The effects of RHO were comparable to those of fluoxetine. Interestingly, neither RHO nor fluoxetine influence the behavioural and physiological parameters tested in non-stressed animals. These findings strongly showed that chronic administration of RHO results in potent inhibition of the behavioural and physiological changes induced by chronic exposure to mild stressors.
Development of an Accessible Audio Computer-Assisted Self-Interview (A-CASI) to Screen for Abuse and Provide Safety Strategies for Women With Disabilities
Authors: Oschwald Mary , Renker Paula , Hughes Rosemary B. , Arthur Anne , Powers Laurie E. , Curry Mary Ann
Published: May 2008

To increase safety and minimize the risk of interpersonal violence, it is critical that women with disabilities and Deaf women have an opportunity to identify whether or not abuse is happening in their lives. Awareness and knowledge of what constitutes abusive behaviors is an essential first step in addressing interpersonal violence. This article includes a description of the development and evaluation of the Safer and Stronger Program (SSP), an audio computer-assisted self-interview program, which was created for women with disabilities and Deaf women for the purposes of increasing awareness of abuse, encouraging safety-planning behaviors, and providing information about community resources.
Domestic Violence Survivors' Access of Career Counseling Services
Authors: Chronister Krista M. , Linville Deanna , Kaag Kristi Palmer
Published: May 2008

The present study was a qualitative investigation of the impact of domestic violence on women's career development and the contextual barriers and supports that affect women's ability to access career counseling services. Our sample included 11 women who completed various stages of a community-based career counseling intervention program. The primary aim of this sampling strategy was to provide career development scholars and counselors with information about the contextual barriers and supports that influence women's decisions to access and complete career counseling services. Data indicated that emotional consequences of abuse, fear of new situations, others' judgments, and practical constraints served as barriers to accessing and completing the career program. Elements of the career group context and the career program structure served as supports to accessing career services. Recommendations for research and practice are provided.
Career Development Concerns of Recent Immigrants and Refugees
Authors: Yakushko Oksana , Backhaus Autumn , Watson Megan , Ngaruiya Katherine , Gonzalez Jaime
Published: May 2008

The number of recent immigrants and refugees in the United States is growing dramatically. Among key reasons for migration is search for adequate employment and hope for opportunities to develop occupationally. However, recent immigrants and refugees face multiple obstacles in their career development in the United States. This article uses social cognitive career theory to examine the role of relocation circumstances, stressors of migration, acculturation patterns, and oppression on the career development and employment functioning of recent immigrants and refugees. Specific suggestions for career counselors working with this population are provided.
School Engagement Among Urban Youth of Color
Authors: Perry Justin C.
Published: May 2008

School engagement is a multifaceted psychosocial process that functions as a key mediator of academic achievement, motivation, and school dropout. This study investigated the effects of vocational exploration and racial identity on behavioral (attendance, attention, time spent on class work) and psychological (identification with school) factors of school engagement among urban youth of color ( N = 197). Hierarchical multiple regression and criterion-pattern analysis revealed a predictive profile marked by high levels of positive racial internalization and career planning combined with low levels of racial dissonance. The study's limitations, directions for research, and implications for practice are discussed.
The Differences in Career-Related Variables Between Temporary and Permanent Employees in Information Technology Companies in Korea
Authors: Tak Jinkook , Lim Beomsik
Published: May 2008

The purpose of this study was to examine differences in career-related variables, such as career commitment and career satisfaction, based on employment status (temporary vs. permanent employees) and job type (professional vs. nonprofessional employees). With a sample of 302 employees working in information technology companies in Korea, it was hypothesized that among the professional employees there would be no significant differences in career-related variables between temporary and permanent employees, whereas among the nonprofessional employees temporary employees would have lower scores of the career-related variables than permanent employees. The hypothesis on career commitment was supported, whereas the hypothesis for career satisfaction was only supported for the nonprofessional employees. These findings suggest that professionalism can increase career commitment for temporary employees. The implications, limitations of the study, and the need for future studies are discussed.
Conceptions of Work in Italian Adults With Intellectual Disability
Authors: Ferrari Lea , Nota Laura , Soresi Salvatore
Published: May 2008

People's ideas about work can greatly affect the ways in which they characterize their own work experience and their lives. The first aim of the present study was to analyze the concept of work in individuals with mild or moderate intellectual disability working in competitive or sheltered work settings and, second, to compare the notions of work of individuals with mental retardation with nondisabled adults and young adolescents. The study therefore examined 48 participants with mental retardation, 48 nondisabled adults of the same chronological age, and 48 nondisabled adolescents of the same mental age as the participants with mental retardation. A semistructured interview assessing participants' concepts about work was administered. Qualitative and quantitative analysis results are discussed. No differences emerged for individuals with MR working in competitive or sheltered work contexts, but were conversely observed among participants with mental retardation, same chronological age adults, and same mental age young adolescents.
Community Foundation Development and Social Capital
Authors: Graddy Elizabeth , Wang Lili
Published: May 2008

The recent worldwide growth of community foundations presents new opportunities for community-based social change. Realizing that promise requires that community foundations sustain the charitable support of their communities with increasing competition for these resources, and thus an understanding of the connection between community characteristics and charitable giving is necessary. The authors focus here on the potential role of community social capital. This study develops and empirically explores a model that connects social capital and gifts to community foundations, while controlling for community demographics and the community's exposure to charitable organizations. The authors find that per capita gifts to community foundations increase with the level of social trust in the community. In addition, gifts are affected by the number of years that community foundations have existed in the region, population density, homeownership, and the poverty rate. Implications are developed for community foundations and for our understanding of the different dimensions of social capital.
Incremental Validity of the Myers-Briggs Type Indicator in Predicting Academic Major Selection of Undecided University Students
Authors: Pulver Chad A. , Kelly Kevin R.
Published: May 2008

This study examined the incremental validity of the Myers-Briggs Type Indicator (MBTI) as a predictor of academic major choice. Undecided university students were administered the MBTI and Strong Interest Inventory (SII). Their academic major choice was recorded at the end of their fourth semester and categorized as realistic, investigative, artistic, social, enterprising, or conventional. We conducted sequential discriminant analyses based on the (a) SII alone and (b) combined use of the SII and MBTI. The SII general occupational theme scales correctly predicted 45.4% of cases, which was significantly better than chance. The hit rate based on the combined use of the SII and MBTI was 48.3%, which was not a significantly higher predictive increment. Implications of these findings for career counselors are discussed.
Mexican American High School Students' Postsecondary Educational Goals
Authors: Flores Lisa Y. , Navarro Rachel L. , DeWitz S. Joseph
Published: May 2008

A multivariate multiple regression analysis predicting the educational goal aspirations and expectations of 89 Mexican American high school students was examined based on Lent, Brown, and Hackett's (1994) Social Cognitive Career Theory and prior research findings with Mexican American samples. No gender or generational status differences were found in educational aspirations or expectations; however, participants reported higher educational aspirations than educational expectations. In addition, results of a multivariate multiple regression analysis suggested that Anglo-oriented acculturation was significantly positively related to educational goal expectations and educational goal aspirations. Mexican-oriented acculturation, college self- efficacy, and college outcome expectations were not significantly related to Mexican American students' educational goals aspirations or expectations. Results are discussed as they relate to improving the educational achievement among Mexican American youth.
Analyzing Public Health Policy: Three Approaches
Authors: Coveney John
Published: May 2008

Policy is an important feature of public and private organizations. Within the field of health as a policy arena, public health has emerged in which policy is vital to decision making and the deployment of resources. Public health practitioners and students need to be able to analyze public health policy, yet many feel daunted by the subject’s complexity. This article discusses three approaches that simplify policy analysis: Bacchi’s “What’s the problem?” approach examines the way that policy represents problems. Colebatch’s governmentality approach provides a way of analyzing the implementation of policy. Bridgman and Davis’s policy cycle allows for an appraisal of public policy development. Each approach provides an analytical framework from which to rigorously study policy. Practitioners and students of public health gain much in engaging with the politicized nature of policy, and a simple approach to policy analysis can greatly assist one’s understanding and involvement in policy work.
A Statewide Strategy for Nursing Workforce Development Through Partnerships in Texas
Authors: Kishi Aileen , Green Alexia
Published: May 2008

Statewide efforts and partnerships were used for nursing workforce development to address the nursing shortage in Texas. A statewide strategic action plan was developed where partnerships and collaboration were the key components. One of the most important outcomes of these statewide partnerships was the passage of the Nursing Shortage Reduction Act 2001. Through this legislation, the Texas Center for Nursing Workforce Studies and its advisory committee were established. This article describes how a statewide infrastructure for nursing workforce policy and legislative and regulatory processes were further developed. An overview is provided on the contributions made by the organizations involved with these strategic partnerships. The ingredients for establishing successful, strategic partnerships are also identified. It is hoped that nursing and health care leaders striving to address the nursing shortage could consider statewide efforts such as those used in Texas to develop nursing workforce policy and legislation.
What Are the Sources of Health Policy That Influence Nursing Practice?
Authors: Taft Susan H. , Nanna Kevin M.
Published: May 2008

This article seeks to fill a gap in the existing nursing literature by answering the question, “Where does health policy come from?” Nursing leaders agree that nurses should be involved in developing health policy, yet most nurses are not engaged. Many factors contribute to nurses' low rates of involvement, but the primary drivers is that nurses believe they lack the knowledge and skills to influence policy formulation. This article proposes a framework of the sources of health policy. We classify health policy sources as public, organizational, or professional, and provide examples. Nurses with a deeper understanding of the varied sources of health policy can enhance their political competence and more readily act in the policy domain.
Treatment and Management of Epilepsy in the Elderly Demented Patient
Authors: Jenssen Sigmund , Schere Daniel
Published: May 2008

Epilepsy and seizures are more frequent in the elderly population than in any other age group. The number of individuals older than 65 is constantly increasing, and dementia is a process that predominantly affects this age group. Several studies have shown that dementia is an important risk factor for developing seizures and epilepsy. Seizure semiology in the elderly demented might differ from that of younger age groups and diagnosis can be complicated further by the variety of other causes of transient changes of alertness and behavior that affects these patients. The pharmacokinetic changes of antiepileptic drugs in the elderly make this group a major therapeutic challenge. Side effects and drug interactions play a major role in the choice of antiepileptic agents. This review intends to summarize the existing data to see whether this can help guide the clinician in the treatment and management of epilepsy in the elderly patient with dementia. Nonpharmacologic therapeutic options are also briefly considered.
Angiostatic activity of the antitumor cytokine interleukin-21
Authors: Castermans Karolien , Tabruyn Sebastien P. , Zeng Rong , van Beijnum Judy R. , Eppolito Cheryl , Leonard Warren J. , Shrikant Protul A. , Griffioen Arjan W.
Published: May 2008

Interleukin-21 (IL-21) is a recently described immunoregulatory cytokine. It has been identified as a very potent immunotherapeutic agent in several cancer types in animal models, and clinical studies are ongoing. IL-21 belongs to the type I cytokine family of which other members, ie, IL-2, IL-15, and IL-4, have been shown to exert activities on vascular endothelial cells (ECs). We hypothesized that IL-21, in addition to inducing the antitumor immune response, also inhibits tumor angiogenesis. In vitro experiments showed a decrease of proliferation and sprouting of activated ECs after IL-21 treatment. We found that the IL-21 receptor is expressed on vascular ECs. Furthermore, in vivo studies in the chorioallantoic membrane of the chick embryo and in mouse tumors demonstrated that IL-21 treatment disturbs vessel architecture and negatively affects vessel outgrowth. Our results also confirm the earlier suggested angiostatic potential of IL-2 in vitro and in vivo. The angiostatic effect of IL-21 is confirmed by the decrease in expression of angiogenesis-related genes. Interestingly, IL-21 treatment of ECs leads to a decrease of Stat3 phosphorylation. Our research shows that IL-21 is a very powerful antitumor compound that combines the induction of an effective antitumor immune response with inhibition of tumor angiogenesis.
Dexamethasone-induced apoptotic mechanisms in myeloma cells investigated by analysis of mutant glucocorticoid receptors
Authors: Sharma Sanjai , Lichtenstein Alan
Published: May 2008

The mechanism by which the glucocorticoid (GC) dexamethasone induces apoptosis in multiple myeloma (MM) cells is unknown, although previous work suggests that either transactivation through the glucocorticoid response element (GRE), transrepression of NF-κB, phosphorylation of RAFTK (Pyk2), or induction of Bim is important. We studied this question by ectopically expressing mutant glucocorticoid receptors (GRs) in the dexamethasone-resistant MM1R cell line, which has lost its GR. Lentiviral-mediated reexpression of wild-type GR restored GRE transactivation, NF-κB transrepression, RAFTK phosphorylation, Bim induction, and dexamethasone-induced apoptosis. We then reexpressed 4 GR mutants, each possessing various molecular effects, into MM1R cells. A perfect correlation was present between induction of GRE transactivation and induction of apoptosis. In contrast, NF-κB transrepression and RAFTK phosphorylation were not required for apoptosis. Although not required for dexamethasone-mediated apoptosis, NF-κB inhibition achieved by gene transfer suggested that NF-κB transrepression could contribute to apoptosis in dexamethasone-treated cells. Dexamethasone treatment of MM1R cells expressing a mutant incapable of inducing apoptosis successfully resulted in RAFTK (Pyk2) phosphorylation and Bim induction indicating the latter GR-mediated events were not sufficient to induce apoptosis. MM1R cells expressing mutant GRs will be helpful in defining the molecular mechanisms of dexamethasone-induced apoptosis of myeloma cells.
Ribosomal protein S19 deficiency in zebrafish leads to developmental abnormalities and defective erythropoiesis through activation of p53 protein family
Authors: Danilova Nadia , Sakamoto Kathleen M. , Lin Shuo
Published: May 2008

Mutations in several ribosomal proteins (RPs) lead to Diamond-Blackfan anemia (DBA), a syndrome characterized by defective erythropoiesis, congenital anomalies, and increased frequency of cancer. RPS19 is the most frequently mutated RP in DBA. RPS19 deficiency impairs ribosomal biogenesis, but how this leads to DBA or cancer remains unknown. We have found that rps19 deficiency in ze-brafish results in hematopoietic and developmental abnormalities resembling DBA. Our data suggest that the rps19-deficient phenotype is mediated by dysregulation of deltaNp63 and p53. During gastrulation, deltaNp63 is required for specification of nonneural ectoderm and its up-regulation suppresses neural differentiation, thus contributing to brain/craniofacial defects. In rps19-deficient embryos, deltaNp63 is induced in erythroid progenitors and may contribute to blood defects. We have shown that suppression of p53 and deltaNp63 alleviates the rps19-deficient phenotypes. Mutations in other ribosomal proteins, such as S8, S11, and S18, also lead to up-regulation of p53 pathway, suggesting it is a common response to ribosomal protein deficiency. Our finding provides new insights into pathogenesis of DBA. Ribosomal stress syndromes represent a broader spectrum of human congenital diseases caused by genotoxic stress; therefore, imbalance of p53 family members may become a new target for therapeutics.
JAK2 stimulates homologous recombination and genetic instability: potential implication in the heterogeneity of myeloproliferative disorders
Authors: Plo Isabelle , Nakatake Mayuka , Malivert Laurent , de Villartay Jean-Pierre , Giraudier Stéphane , Villeval Jean-Luc , Wiesmuller Lisa , Vainchenker William
Published: May 2008

The JAK2V617F mutation is frequently observed in classical myeloproliferative disorders, and disease progression is associated with a biallelic acquisition of the mutation occurring by mitotic recombination. In this study, we examined whether JAK2 activation could lead to increased homologous recombination (HR) and genetic instability. In a Ba/F3 cell line expressing the erythropoietin (EPO) receptor, mutant JAK2V617F and, to a lesser extent, wild-type (wt) JAK2 induced an increase in HR activity in the presence of EPO without modifying nonhomologous end-joining efficiency. Moreover, a marked augmentation in HR activity was found in CD34+-derived cells isolated from patients with polycythemia vera or primitive myelofibrosis compared with control samples. This increase was associated with a spontaneous RAD51 foci formation. As a result, sister chromatid exchange was 50% augmented in JAK2V617F Ba/F3 cells compared with JAK2wt cells. Moreover, JAK2 activation increased centrosome and ploidy abnormalities. Finally, in JAK2V617F Ba/F3 cells, we found a 100-fold and 10-fold increase in mutagenesis at the HPRT and Na/K ATPase loci, respectively. Together, this work highlights a new molecular mechanism for HR regulation mediated by JAK2 and more efficiently by JAK2V617F. Our study might provide some keys to understand how a single mutation can give rise to different pathologies.
Protein contact order prediction from primary sequences
Authors: Shi Yi , Zhou Jianjun , Arndt David , Wishart David S , Lin Guohui
Published: May 2008

Background

Contact order is a topological descriptor that has been shown to be correlated with several interesting protein properties such as protein folding rates and protein transition state placements. Contact order has also been used to select for viable protein folds from ab initio protein structure prediction programs. For proteins of known three-dimensional structure, their contact order can be calculated directly. However, for proteins with unknown three-dimensional structure, there is no effective prediction method currently available.

Results

In this paper, we propose several simple yet very effective methods to predict contact order from the amino acid sequence only. One set of methods is based on a weighted linear combination of predicted secondary structure content and amino acid composition. Depending on the number of components used in these equations it is possible to achieve a correlation coefficient of 0.857–0.870 between the observed and predicted contact order. A second method, based on sequence similarity to known three-dimensional structures, is able to achieve a correlation coefficient of 0.977. We have also developed a much more robust implementation for calculating contact order directly from PDB coordinates that works for > 99% PDB files. All of these contact order predictors and calculators have been implemented as a web server (see Availability and requirements section for URL).

Conclusion

Protein contact order can be effectively predicted from the primary sequence, at the absence of three-dimensional structure. Three factors, percentage of residues in alpha helices, percentage of residues in beta strands, and sequence length, appear to be strongly correlated with the absolute contact order.
Smoking-induced gene expression changes in the bronchial airway are reflected in nasal and buccal epithelium
Authors: Sridhar Sriram , Schembri Frank , Zeskind Julie , Shah Vishal , Gustafson Adam M , Steiling Katrina , Liu Gang , Dumas Yves-Martine , Zhang Xiaohui , Brody Jerome S , Lenburg Marc E , Spira Avrum
Published: May 2008

Background

Cigarette smoking is a leading cause of preventable death and a significant cause of lung cancer and chronic obstructive pulmonary disease. Prior studies have demonstrated that smoking creates a field of molecular injury throughout the airway epithelium exposed to cigarette smoke. We have previously characterized gene expression in the bronchial epithelium of never smokers and identified the gene expression changes that occur in the mainstem bronchus in response to smoking. In this study, we explored relationships in whole-genome gene expression between extrathorcic (buccal and nasal) and intrathoracic (bronchial) epithelium in healthy current and never smokers.

Results

Using genes that have been previously defined as being expressed in the bronchial airway of never smokers (the "normal airway transcriptome"), we found that bronchial and nasal epithelium from non-smokers were most similar in gene expression when compared to other epithelial and nonepithelial tissues, with several antioxidant, detoxification, and structural genes being highly expressed in both the bronchus and nose. Principle component analysis of previously defined smoking-induced genes from the bronchus suggested that smoking had a similar effect on gene expression in nasal epithelium. Gene set enrichment analysis demonstrated that this set of genes was also highly enriched among the genes most altered by smoking in both nasal and buccal epithelial samples. The expression of several detoxification genes was commonly altered by smoking in all three respiratory epithelial tissues, suggesting a common airway-wide response to tobacco exposure.

Conclusion

Our findings support a relationship between gene expression in extra- and intrathoracic airway epithelial cells and extend the concept of a smoking-induced field of injury to epithelial cells that line the mouth and nose. This relationship could potentially be utilized to develop a non-invasive biomarker for tobacco exposure as well as a non-invasive screening or diagnostic tool providing information about individual susceptibility to smoking-induced lung diseases.
Diagnostic utility of LunXmRNA in peripheral blood and pleural fluid in patients with primary non-small cell lung cancer
Authors: Cheng Min , Chen Yongyan , Yu Xiaoqing , Tian Zhigang , Wei Haiming
Published: May 2008

Background

Progress in lung cancer is hampered by the lack of clinically useful diagnostic markers. The goal of this study was to provide a detailed evaluation of lung cancer tumor markers indicative of molecular abnormalities and to assess their diagnostic utility in non-small cell lung cancer (NSCLC) patients.

Methods

Quantitative real-time RT-PCR was used to determine LunX, CK19, CEA, VEGF-C and hnRNP A2/B1 mRNA levels in peripheral blood and pleural fluid from NSCLC patients, compared with those from patients with other epithelial cancer (esophagus cancer and breast cancer), benign lung disease (pneumonia and tuberculo pleurisy) and from healthy volunteers.

Results

In peripheral blood LunX mRNA was detectable in 75.0% (33/44) of patients with NSCLC, but not in patients with other epithelial cancer (0/28), benign lung disease (0/10) or in healthy volunteers (0/15). In contrast, all other genetic markers were detected in patients with either NSCLC, other epithelia cancer or benign lung disease, and in healthy volunteers. The expression level and positive rate of LunX mRNA in peripheral blood correlated with the pathologic stage of NSCLC (P < 0.001 and P = 0.010 respectively). Furthermore, LunX mRNA was detected in 92.9% (13/14) of malignant pleural fluid samples and was the only marker whose expression level was significantly different between malignant and benign pleural fluid (P < 0.001). Additionally, expression of LunX mRNA in the peripheral blood of NSCLC patients decreased shortly after clinical treatment (P = 0.005).

Conclusion

Of several commonly used genetic markers, LunX mRNA is the most specific gene marker for lung cancer and has potential diagnostic utility when measured in the peripheral blood and pleural fluid of NSCLC patients.
CUSP: an algorithm to distinguish structurally conserved and unconserved regions in protein domain alignments and its application in the study of large length variations
Authors: Sandhya Sankaran , Pankaj Barah , Govind Madabosse Kande , Offmann Bernard , Srinivasan Narayanaswamy , Sowdhamini Ramanathan
Published: May 2008

Background

Distantly related proteins adopt and retain similar structural scaffolds despite length variations that could be as much as two-fold in some protein superfamilies. In this paper, we describe an analysis of indel regions that accommodate length variations amongst related proteins. We have developed an algorithm CUSP, to examine multi-membered PASS2 superfamily alignments to identify indel regions in an automated manner. Further, we have used the method to characterize the length, structural type and biochemical features of indels in related protein domains.

Results

CUSP, examines protein domain structural alignments to distinguish regions of conserved structure common to related proteins from structurally unconserved regions that vary in length and type of structure. On a non-redundant dataset of 353 domain superfamily alignments from PASS2, we find that 'length- deviant' protein superfamilies show > 30% length variation from their average domain length. 60% of additional lengths that occur in indels are short-length structures (< 5 residues) while 6% of indels are > 15 residues in length. Structural types in indels also show class-specific trends.

Conclusion

The extent of length variation varies across different superfamilies and indels show class-specific trends for preferred lengths and structural types. Such indels of different lengths even within a single protein domain superfamily could have structural and functional consequences that drive their selection, underlying their importance in similarity detection and computational modelling. The availability of systematic algorithms, like CUSP, should enable decision making in a domain superfamily-specific manner.
In vitro effects of selenium deficiency on West Nile virus replication and cytopathogenicity
Authors: Verma Saguna , Molina Yanira , Lo Yeung Y , Cropp Bruce , Nakano Cheynie , Yanagihara Richard , Nerurkar Vivek R
Published: May 2008

Background

Selenium (Se) deficiency plays an important role in viral pathogenesis. To understand the effects of Se deficiency on West Nile virus (WNV) infection, we analyzed cytopathogenicity, apoptosis and viral replication kinetics, using a newly developed Se-deficient cell culture system.

Results

Both Vero and SK-N-SH cells grown in Se-deficient media exhibited a gradual loss of glutathione peroxidase (GPx1) activity without any significant effect on cell growth and viability. In SK-N-SH cells, Se deficiency had no effect on the expression of key antioxidant enzymes, including manganese- and copper-zinc superoxide dismutase (MnSOD and CuZnSOD), catalase and inducible nitric oxide synthase, whereas Vero cells demonstrated a significant increase in the expression of MnSOD and an overall increase in oxidative stress (OS) at day 7 post-induction of Se deficiency. At 2 days after infection with WNV, CPE and cell death were significantly higher in WNV-infected Se-deficient Vero cells, compared to WNV-infected control cells. Furthermore, WNV-induced apoptosis was significantly heightened in Se-deficient cells and was contributed by loss of mitochondrial membrane potential and increased caspase activity. However, no significant difference was found in WNV copy numbers between control, Se-adequate and Se-deficient cell cultures.

Conclusion

Overall results demonstrate that the in vitro Se-deficient model can be used to study responses of WNV to this essential nutrient. Although Se deficiency has no in vitro effect on WNV replication kinetics, adequate Se is presumably critical to protect WNV-infected cells against virus-induced cell death.
Prevalence of four different subgenotypes of genotype 4 hepatitis E virus among swine in the Shanghai area of China
Authors: Yan Yijia , Zhang Wen , Shen Quan , Cui Li , Hua Xiuguo
Published: May 2008

Background

Hepatitis E virus (HEV) is a zoonotic pathogen of which swine was reported as major reservoirs. HEV has been divided into 4 different genotypes according to phylogenetic analysis. Recent reports showed that genotype 4 HEV is freely transmitted between humans and swine in eastern China, including Shanghai area. This paper investigated the recent infection status of HEV among swine population of Shanghai area in China.

Methods

480 swine faecal specimens were collected from 23 farms which distribute all over Shanghai from September to November, 2007 and tested for the presence of HEV RNA by the polymerase chain reaction (PCR).

Results

Our results showed that 26.1% (6/23) of the swine farms were positive for HEV RNA and the positive rate of the six farms were ranged from 9.1% to 33.3%. The HEV RNA positive rate for total samples were 5% (24/480). The resulted positive band specific for HEV was sequenced and sequence analysis indicated that all of these isolates belonged to genotype 4 HEV. Phylogenetic analysis showed that the 24 isolates clustered into 4 distinct subgroups, sharing 83.3–89.7% inter-subgroup and 97–99% intra-subgroup identities. More over, isolates in three of the four subgroups closely clustered with previous identified strains, sharing up high to 97% identity with them.

Conclusion

These results suggested that there were 4 different subgenotypes of HEV prevalent in Shanghai, and some of them may not be indigenous to Shanghai but introduced from other geographic regions.
Surgical treatment and outcome of pulmonary hamartoma: a retrospective study of 20-year experience
Authors: Guo Wei , Zhao Yun-Ping , Jiang Yao-Guang , Wang Ru-Wen , Ma Zheng
Published: May 2008

Background

Controversy still exists in the indication and timing of surgical treatment of pulmonary hamartoma (PH). The objective of this study is to summarize the experience and the outcome of the surgical treatment for pulmonary hamartomas, and to assess the effectiveness and necessity of surgical therapy administered in patients with pulmonary hamatoma as well as clinical and pathological features and long-term follow-up results.

Methods

This retrospective report has reviewed a 20-years clinical history of surgical treatment for 39 patients with PH from 1985 to 2006. These thirty-nine patients underwent 40 operations as follows: wedge resection (23), enucleation (10), segmentectomy (3), lobectomy (3), and pneumonectomy (1).

Results

The PH occurred most frequently (78.1%) in the patients aged 40 to 60 years and the sex ratio (male/female) was 2.25/1 in our series. No postoperative death was encountered. One patient with pleural effusion was cured after thoracentesis. All of these 39 patients were proved with pathologic diagnosis of PH and the popcorn calcification was found in 6 cases before operation. In 38 cases having the mean follow-up of 7.3 years, a patient was operated thrice for regional recurrence.

Conclusion

Fast frozen section in operation is critical for acquire accurate pathological diagnosis. Due to potential trend of recurrence or malignance, patients with hamartoma should be submitted to a complete evaluation and a regular follow-up.
Heme oxygenase-1 expression is down-regulated by angiotensin II and under hypertension in human neutrophils
Authors: Alba Gonzalo , El Bekay Rajaa , Chacón Pedro , Reyes M Edith , Ramos Eladio , Oliván Josefina , Jiménez Juan , López José M , Martín-Nieto José , Pintado Elízabeth , Sobrino Francisco
Published: May 2008

Angiotensin II (Ang II) is a peptide hormone able to elicit a strong production of reactive oxygen species by human neutrophils. In this work, we have addressed whether expression of heme oxygenase-1 (HO-1), an antioxidant enzyme, becomes altered in these cells upon Ang II treatment or under hypertension conditions. In neutrophils from healthy and hypertensive subjects, induction of HO-1 mRNA and protein expression with a parallel increase in enzyme activity took place upon treatment with 15-deoxy-Δ12,14-PGJ2 (15dPGJ2). However, Ang II prevented HO-1 synthesis by normal neutrophils in vitro, and HO-1 expression was depressed in neutrophils from hypertensive patients in comparison with cells from healthy subjects. In addition, Ang II treatment led to a reduced HO-1 enzyme activity to levels similar to those found in neutrophils from hypertensive patients. NO donors reversed the inhibition of 15dPGJ2-dependent HO-1 expression in neutrophils from hypertensive patients, and conversely, inhibition of inducible NO synthase (NOS2) activity counteracted the stimulatory effect of 15dPGJ2 on HO-1 expression in normal human neutrophils. Moreover, Ang II canceled 15dPGJ2-dependent induction of NOS2 mRNA synthesis. Present findings indicate that down-regulation of HO-1 expression in neutrophils from hypertensive subjects is likely exerted through the inhibition of NOS2 expression. Additionally, they underscore the potential usefulness of NO donors as new, therapeutic agents against hypertension.
Selected natural and synthetic retinoids impair CCR7- and CXCR4-dependent cell migration in vitro and in vivo
Authors: Villablanca Eduardo J , Zhou Dan , Valentinis Barbara , Negro Aurora , Raccosta Laura , Mauri Laura , Prinetti Alessandro , Sonnino Sandro , Bordignon Claudio , Traversari Catia , Russo Vincenzo
Published: May 2008

Dendritic cell (DC) migration to secondary lymphoid organs is a crucial step to initiate adaptive immune responses. This step requires the expression of a functional CCR7 chemokine receptor on DC undergoing maturation. Here, we show that the natural retinoid 9-cis retinoic acid (9cRA) and the synthetic retinoid fenretinide (4-HPR) specifically inhibit the functional up-regulation of CCR7 on maturing human DCs, without affecting early steps of DC maturation. As a consequence, mature DCs do not migrate in vitro toward the chemokine CCL19. Importantly, 4-HPR and 9cRA by inhibiting the expression of CCR7 on bone marrow-derived murine DCs dampen their in vivo migration to draining lymph nodes. 4-HPR also inhibits the expression of the chemokine receptors CXCR4, therefore, impairing in vitro migration of human DCs to CXCL12 and inhibiting in vivo the CXCR4-dependent migration of the posterior lateral line primordium (PLLp) in zebrafish embryos. Taken together, these data highlight a novel function of retinoids and suggest the possibility of using retinoids to treat inflammatory or autoimmune diseases.