bluuebunny/crossref_metadata_2025 huggingface dataset:
Enacting solidarity and ambivalence: Positional identities of Arab American women
Authors: Mango Oraib
Published: September 2010

In this research, I investigate how a group of Arab American women constructed their identities through their talk during focus group discussions. The research is based on a sociocultural view of identity as primarily social, and inclusive of the positions and roles that a person takes during moment-to-moment interaction and discourse (Bucholtz and Hall, 2005). This is compatible with a view of identity and discourse as interrelated and interdependent (Norton, 2000). I relied heavily on Bucholtz and Hall’s (2005) proposed framework for analyzing identities in talk. The results indicated that the women’s positionings of themselves through talk were characterized by affiliation toward each other and were imbued with ambivalence and uncertainty, thus pointing toward identities in the making.
The use of okay, right and yeah in academic lectures by native speaker lecturers: Their ‘anticipated’ and ‘real’ meanings
Authors: Othman Zarina
Published: September 2010

This article demonstrates the ‘patterning’ of the ways discourse markers such as okay , right and yeah are used in academic lectures by native speaker lecturers. It presents an analysis of a) what the lecturers thought they would say and b) what they actually say in comparison to what the lecturers actually do say. In other words, it focuses on the differences between expectations of what would be said and speech, that is, what is actually said.The data comprise verbatim lecture transcriptions of four native speaker lecturers of different disciplines, analysed using a discourse analytical approach. The findings and discussions exhibit the reasons for the differences between the ‘anticipated’ and ‘real’ meanings of the use of these discourse markers.They also reflect upon the significance of non-verbal features in determining the actual functions of these markers. In short, this article highlights the reality use of okay, right and yeah as interactive conversational markers in academic lectures.
Liberal recognition for identity? Only for particularized ones
Authors: Akhtar Sahar
Published: September 2010

Communitarian writers argue that social identity is deeply important to individual autonomy and thus liberal societies have an obligation to recognize identity. Any liberal view that attempts to account for this charge must specify a procedure to recognize identity that also ensures that the liberal sense of autonomy is not weakened. In this article, I develop such an account. I argue that liberals must distinguish an identity that belongs to particular persons (particularized identity) from the collective form of that identity. For instance, Naisha will have her own particularized way of being Indian in addition to the collective form of the culture that she shares with others. To determine which acts would be about recognizing the particularized form, I provide a counterfactual test. One major implication of the test is that special collective rights would not be endorsed. At the same time, the test is not equivalent to the liberal positions of insisting either that rights belong to individuals or that individuals are not harmed. Because identity is almost always viewed in terms of groups, valuing identity seems to be at odds with the principles of liberalism and democratic theory in which individual persons are the ultimate source of value. I show that there is a significant way to recognize identity that is harmonious with these principles.
Modelling multivariate disease rates with a latent structure mixture model
Authors: Hewson PJ , Bailey TC
Published: September 2010

There has been considerable recent interest in multivariate modelling of the geographical distribution of morbidity or mortality rates for potentially related diseases. The motivations for this include investigation of similarities or dissimilarities in the risk distribution for the different diseases, as well as ‘borrowing strength’ across disease rates to shrink the uncertainty in geographical risk assessment for any particular disease. A number of approaches to such multivariate modelling have been suggested and this paper proposes an extension to these which may provide a richer range of dependency structures than those encompassed so far. We develop a model which incorporates a discrete mixture of latent structures and argue that this provides potential to represent an enhanced range of correlation structures between diseases at the same time as implicitly allowing for less restrictive spatial correlation structures between geographical units. We compare and contrast our approach to other commonly used multivariate disease models and demonstrate comparative results using data taken from cancer registries on four carcinomas in some 300 geographical units in England, Scotland and Wales.
Robust frailty modelling using non-proportional hazards models
Authors: Ha Il Do , MacKenzie Gilbert
Published: September 2010

Correlated survival times can be modelled by introducing a random effect, or frailty component, into the hazard function. For multivariate survival data, we extend a non-proportional hazards (PH) model, the generalized time-dependent logistic survival model, to include random effects. The hierarchical likelihood procedure, which obviates the need for marginalization over the random effect distribution, is derived for this extended model and its properties are discussed. The extended model leads to a robust estimation result for the regression parameters against the misspecification of the form of the basic hazard function or frailty distribution compared to PH-based alternatives. The proposed method is illustrated by two practical examples and a simulation study which demonstrate the advantages of the new model.
Small-dense LDL and LDL glycation in metabolic syndrome and in statin-treated and non-statin-treated type 2 diabetes
Authors: Younis Nahla N , Soran Handrean , Sharma Reena , Charlton-Menys Valentine , Greenstein Adam , Elseweidy Mohamed M , Durrington Paul N
Published: September 2010

Small-dense LDL (SD-LDL) has been particularly implicated in atherosclerosis. It has previously been reported that in non-diabetic people SD-LDL is preferentially glycated. The distribution of glycated apolipoprotein B (glyc-apoB) in lipoproteins in metabolic syndrome (MS) and in type 2 diabetes has not previously been studied.

Plasma apoB and glyc-apoB were determined in different apoB-containing lipoproteins including buoyant and SD-LDL in MS ( n=18) and type 2 diabetes (DM) [ n=48; 12 statin-untreated (DM−S) and 36 statin-treated (DM+S)].

Plasma glyc-apoB was 5.6 ± 0.9, 3.5 ± 0.5 and 4.0 ± 0.2 mg/dl in DM−S, DM+S and MS, respectively. The glycated proportion of SD-LDL-apoB was greater than buoyant LDL in all groups. SD-LDL contributed most to plasma glyc-apoB in DM−S, because SD-LDL-apoB was higher in DM−S than in MS and DM+S ( p < 0.001). Plasma glyc-apoB correlated with SD-LDL-apoB ( r=0.74, p < 0.0001 in diabetes and r=0.53, p < 0.001 in MS), but not with HbA1c.

SD-LDL is preferentially glycated in type 2 diabetes and MS. Its concentration is a stronger determinant of plasma glycapoB than glycaemia. Statin-induced changes in its level may be important in decreasing apoB glycation in diabetes. These findings may explain the small effect of improving glycaemia relative to statin treatment in reducing atherosclerosis risk in type 2 diabetes and the increased risk in MS even before the onset of type 2 diabetes.
Aluminum adjuvants elicit fibrin-dependent extracellular traps in vivo
Authors: Munks Michael W. , McKee Amy S. , MacLeod Megan K. , Powell Roger L. , Degen Jay L. , Reisdorph Nichole A. , Kappler John W. , Marrack Philippa
Published: September 2010

It has been recognized for nearly 80 years that insoluble aluminum salts are good immunologic adjuvants and that they form long-lived nodules in vivo. Nodule formation has long been presumed to be central for adjuvant activity by providing an antigen depot, but the composition and function of these nodules is poorly understood. We show here that aluminum salt nodules formed within hours of injection and contained the clotting protein fibrinogen. Fibrinogen was critical for nodule formation and required processing to insoluble fibrin by thrombin. DNase treatment partially disrupted the nodules, and the nodules contained histone H3 and citrullinated H3, features consistent with extracellular traps. Although neutrophils were not essential for nodule formation, CD11b+ cells were implicated. Vaccination of fibrinogen-deficient mice resulted in normal CD4 T-cell and antibody responses and enhanced CD8 T-cell responses, indicating that nodules are not required for aluminum's adjuvant effect. Moreover, the ability of aluminum salts to retain antigen in the body, the well-known depot effect, was unaffected by the absence of nodules. We conclude that aluminum adjuvants form fibrin-dependent nodules in vivo, that these nodules have properties of extracellular traps, and the nodules are not required for aluminum salts to act as adjuvants.
Intracoronary shear-related up-regulation of platelet P-selectin and platelet-monocyte aggregation despite the use of aspirin and clopidogrel
Authors: Yong Andy S. C. , Pennings Gabrielle J. , Chang Michael , Hamzah Afiqah , Chung Tommy , Qi Miao , Brieger David , Behnia Masud , Krilis Steven A. , Ng Martin K.C. , Lowe Harry C. , Kritharides Leonard
Published: September 2010

Recent in vitro studies have shown that shear stress can cause platelet activation by agonist-independent pathways. However, no studies have assessed the extent of shear-induced platelet activation within human coronary arteries. We sampled blood from the coronary arteries proximal and distal to coronary lesions and from the coronary sinus in humans with stable coronary disease who were taking both aspirin and clopidogrel. A novel, computationally based technique for estimating shear stress from 3-dimensional coronary angiographic images of these arteries was developed, and the effect of stenosis severity and calculated shear stress on in vivo platelet and related leukocyte activation pathways were determined. We provide evidence of intracoronary up-regulation of platelet P-selectin, platelet-monocyte aggregation, and monocyte CD11b without platelet glycoprotein IIb-IIIa activation or soluble P-selectin up-regulation. This correlates with intracoronary stenosis severity and calculated shear stress and occurs despite the concurrent use of aspirin and clopidogrel. Our results show for the first time shear-related platelet and monocyte activation in human coronary arteries and suggest this as a potential therapeutic target that is resistant to conventional antiplatelet agents.
Regulation of platelet myosin light chain (MYL9) by RUNX1: implications for thrombocytopenia and platelet dysfunction in RUNX1 haplodeficiency
Authors: Jalagadugula Gauthami , Mao Guangfen , Kaur Gurpreet , Goldfinger Lawrence E. , Dhanasekaran Danny N. , Rao A. Koneti
Published: September 2010

Mutations in transcription factor RUNX1 are associated with familial platelet disorder, thrombocytopenia, and predisposition to leukemia. We have described a patient with thrombocytopenia and impaired agonist-induced platelet aggregation, secretion, and glycoprotein (GP) IIb-IIIa activation, associated with a RUNX1 mutation. Platelet myosin light chain (MLC) phosphorylation and transcript levels of its gene MYL9 were decreased. Myosin IIA and MLC phosphorylation are important in platelet responses to activation and regulate thrombopoiesis by a negative regulatory effect on premature proplatelet formation. We addressed the hypothesis that MYL9 is a transcriptional target of RUNX1. Chromatin immunoprecipitation (ChIP) using megakaryocytic cells revealed RUNX1 binding to MYL9 promoter region −729/−542 basepairs (bp), which contains 4 RUNX1 sites. Electrophoretic mobility shift assay showed RUNX1 binding to each site. In transient ChIP assay, mutation of these sites abolished binding of RUNX1 to MYL9 promoter construct. In reporter gene assays, deletion of each RUNX1 site reduced activity. MYL9 expression was inhibited by RUNX1 short interfering RNA (siRNA) and enhanced by RUNX1 overexpression. RUNX1 siRNA decreased cell spreading on collagen and fibrinogen. Our results constitute the first evidence that the MYL9 gene is a direct target of RUNX1 and provide a mechanism for decreased platelet MYL9 expression, MLC phosphorylation, thrombocytopenia, and platelet dysfunction associated with RUNX1 mutations.
Protein network prediction and topological analysis in Leishmania major as a tool for drug target selection
Authors: Flórez Andrés F , Park Daeui , Bhak Jong , Kim Byoung-Chul , Kuchinsky Allan , Morris John H , Espinosa Jairo , Muskus Carlos
Published: September 2010

Background

Leishmaniasis is a virulent parasitic infection that causes a worldwide disease burden. Most treatments have toxic side-effects and efficacy has decreased due to the emergence of resistant strains. The outlook is worsened by the absence of promising drug targets for this disease. We have taken a computational approach to the detection of new drug targets, which may become an effective strategy for the discovery of new drugs for this tropical disease.

Results

We have predicted the protein interaction network ofLeishmania majorby using three validated methods: PSIMAP, PEIMAP, and iPfam. Combining the results from these methods, we calculated a high confidence network (confidence score > 0.70) with 1,366 nodes and 33,861 interactions. We were able to predict the biological process for 263 interacting proteins by doing enrichment analysis of the clusters detected. Analyzing the topology of the network with metrics such as connectivity and betweenness centrality, we detected 142 potential drug targets after homology filtering with the human proteome. Further experiments can be done to validate these targets.

Conclusion

We have constructed the first protein interaction network of theLeishmania majorparasite by using a computational approach. The topological analysis of the protein network enabled us to identify a set of candidate proteins that may be both (1) essential for parasite survival and (2) without human orthologs. These potential targets are promising for further experimental validation. This strategy, if validated, may augment established drug discovery methodologies, for this and possibly other tropical diseases, with a relatively low additional investment of time and resources.
Evolutionary lability of a complex life cycle in the aphid genus Brachycaudus
Authors: Jousselin Emmanuelle , Genson Gwenaelle , Coeur d'acier Armelle
Published: September 2010

Background

Most aphid species complete their life cycle on the same set of host-plant species, but some (heteroecious species) alternate between different hosts, migrating from primary (woody) to secondary (herbaceous) host plants. The evolutionary processes behind the evolution of this complex life cycle have often been debated. One widely accepted scenario is that heteroecy evolved from monoecy on woody host plants. Several shifts towards monoecy on herbaceous plants have subsequently occurred and resulted in the radiation of aphids. Host alternation would have persisted in some cases due to developmental constraints preventing aphids from shifting their entire life cycle to herbaceous hosts (which are thought to be more favourable). According to this scenario, if aphids lose their primary host during evolution they should not regain it. The genusBrachycaudusincludes species with all the types of life cycle (monoecy on woody plants, heteroecy, monoecy on herbs). We used this genus to test hypotheses concerning the evolution of life cycles in aphids.

Results

Phylogenetic investigation and character reconstruction suggest that life cycle is evolutionary labile in the genus. Though ancestral character states can be ambiguous depending on optimization methods, all analyses suggest that transitions from monoecy on herbs towards heteroecy have occurred several times. Transitions from heteroecy towards monoecy, are also likely. There have been many shifts in feeding behaviour but we found no significant correlation between life cycle changes and changes in diet.

Conclusions

The transitions from monoecy on herbs towards heteroecy observed in this study go against a widely accepted evolutionary scenario: aphids in the genusBrachycaudusseem to be able to recapture their supposedly ancestral woody host. This suggests that the determinants of host alternation are probably not as complicated as previously thought. Definitive proofs of the lability of life cycle inBrachycauduswill necessitate investigation of these determinants. Life cycle changes, whether corresponding to the loss or acquisition of a primary host, necessarily promote speciation, by inducing shifts of the reproductive phase on different plants. We suggest that the evolutionary lability of life cycle may have driven speciation events in theBrachycaudusgenus.
Genome-wide conserved consensus transcription factor binding motifs are hyper-methylated
Authors: Choy Mun-Kit , Movassagh Mehregan , Goh Hock-Guan , Bennett Martin R , Down Thomas A , Foo Roger SY
Published: September 2010

Background

DNA methylation can regulate gene expression by modulating the interaction between DNA and proteins or protein complexes. Conserved consensus motifs exist across the human genome ("predicted transcription factor binding sites": "predicted TFBS") but the large majority of these are proven by chromatin immunoprecipitation and high throughput sequencing (ChIP-seq) not to be biological transcription factor binding sites ("empirical TFBS"). We hypothesize that DNA methylation at conserved consensus motifs prevents promiscuous or disorderly transcription factor binding.

Results

Using genome-wide methylation maps of the human heart and sperm, we found that all conserved consensus motifs as well as the subset of those that reside outside CpG islands have an aggregate profile of hyper-methylation. In contrast, empirical TFBS with conserved consensus motifs have a profile of hypo-methylation. 40% of empirical TFBS with conserved consensus motifs resided in CpG islands whereas only 7% of all conserved consensus motifs were in CpG islands. Finally we further identified a minority subset of TF whose profiles are either hypo-methylated or neutral at their respective conserved consensus motifs implicating that these TF may be responsible for establishing or maintaining an un-methylated DNA state, or whose binding is not regulated by DNA methylation.

Conclusions

Our analysis supports the hypothesis that at least for a subset of TF, empirical binding to conserved consensus motifs genome-wide may be controlled by DNA methylation.
Proteomic analysis of Salmonella enterica serovar Enteritidis following propionate adaptation
Authors: Calhoun Leona N , Liyanage Rohana , Lay Jackson O , Kwon Young Min
Published: September 2010

Background

Salmonella Enteritidis is a highly prevalent and persistent foodborne pathogen and is therefore a leading cause of nontyphoidal gastrointestinal disease worldwide. A variety of stresses are endured throughout its infection cycle, including high concentrations of propionate (PA) within food processing systems and within the gut of infected hosts. Prolonged PA exposure experienced in such milieus may have a drastic effect on the proteome of Salmonella Enteritidis subjected to this stress.

Results

In this study, we used 2 D gel electrophoresis to examine the proteomes of PA adapted and unadapted S. Enteritidis and have identified five proteins that are upregulated in PA adapted cultures using standard peptide mass fingerprinting by MALDI-TOF-MS and sequencing by MALDI LIFT-TOF/TOF tandem mass spectrometry. Of these five, two significant stress-related proteins (Dps and CpxR) were shown (via qRT-PCR analysis) to be upregulated at the transcriptional level as well. Unlike the wild type when adapted to PA (which demonstrates significant acid resistance), PA adapted S. Enteritidis ∆dps and S. Enteritidis ∆cpxR were at a clear disadvantage when challenged to a highly acidic environment. However, we found the acid resistance to be fully restorable after genetic complementation.

Conclusions

This work reveals a significant difference in the proteomes of PA adapted and unadapted S. Enteritidis and affirms the contribution of Dps and CpxR in PA induced acid resistance.
Characterization, sub-cellular localization and expression profiling of the isoprenylcysteine methylesterase gene family in Arabidopsis thaliana
Authors: Lan Ping , Li Wenfeng , Wang Huizhong , Ma Wujun
Published: September 2010

Background

Isoprenylcysteine methylesterases (ICME) demethylate prenylated protein in eukaryotic cell. Until now, knowledge about their molecular information, localization and expression pattern is largely unavailable in plant species. One ICME in Arabidopsis, encoded by At5g15860, has been identified recently. Over-expression of At5g15860 caused an ABA hypersensitive phenotype in transgenic Arabidopsis plants, indicating that it functions as a positive regulator of ABA signaling. Moreover, ABA induced the expression of this gene in Arabidopsis seedlings. The current study extends these findings by examining the sub-cellular localization, expression profiling, and physiological functions of ICME and two other ICME-like proteins, ICME-LIKE1 and ICME-LIKE2, which were encoded by two related genes At1g26120 and At3g02410, respectively.

Results

Bioinformatics investigations showed that the ICME and other two ICME-like homologs comprise a small subfamily of carboxylesterase (EC 3.1.1.1) in Arabidopsis. Sub-cellular localization of GFP tagged ICME and its homologs showed that the ICME and ICME-like proteins are intramembrane proteins predominantly localizing in the endoplasmic reticulum (ER) and Golgi apparatus. Semi-quantitative and real-time quantitative PCR revealed that the ICME and ICME-like genes are expressed in all examined tissues, including roots, rosette leaves, cauline leaves, stems, flowers, and siliques, with differential expression levels. Within the gene family, the base transcript abundance of ICME-LIKE2 gene is very low with higher expression in reproductive organs (flowers and siliques). Time-course analysis uncovered that both ICME and ICME-like genes are up-regulated by mannitol, NaCl and ABA treatment, with ICME showing the highest level of up-regulation by these treatments. Heat stress resulted in up-regulation of the ICME gene significantly but down-regulation of the ICME-LIKE1 and ICME-LIKE2 genes. Cold and dehydration stimuli led to no significant change of both ICME and ICME-like gene expression. Mutant icme-like2-1 showed increased sensitivity to ABA but slightly decreased sensitivity to salt and osmotic stresses during seed germination.

Conclusions

It is concluded that the ICME family is involved in stress and ABA signaling in Arabidopsis, probably through mediating the process of demethylating prenylated proteins. Identification of these prenylated proteins will help to better understand the significance of protein prenylation in Planta.
Gross genomic alterations and gene expression profiles of high- grade serous carcinoma of the ovary with and without BRCA1 inactivation
Authors: Pradhan Manohar , Risberg Björn Å , Tropé Claes G , van de Rijn Matt , Gilks C Blake , Lee Cheng-Han
Published: September 2010

Background

BRCA1 gene inactivation causes chromosomal instability, leading to rapid accumulation of chromosomal rearrangements and mutations. The loss of BRCA1 function due to either germline/somatic mutation or epigenetic silencing is observed in most high-grade serous carcinomas of the ovary.

Methods

DNA ploidy and gene expression profile were used in order to compare gross genomic alteration and gene expression pattern between cases with BRCA1 loss through mutation, BRCA1 epigenetic loss, and no BRCA1 loss in cases of high-grade serous carcinoma with known BRCA1 and BRCA 2 status.

Results

Using image cytometry and oligonucleotide microarrays, we analyzed DNA ploidy, S-phase fraction and gene expression profile of 28 consecutive cases of ovarian high-grade serous adenocarcinomas, which included 8 tumor samples with BRCA1 somatic or germline mutation, 9 samples with promoter hypermethylation of BRCA1, and 11 samples with no BRCA1 loss. None had BRCA2 mutations. The prevalence of aneuploidy and tetraploidy was not statistically different in the three groups with different BRCA1 status. The gene expression profiles were also very similar between the groups, with only two genes showing significant differential expression when comparison was made between the group with BRCA1 mutation and the group with no demonstrable BRCA1 loss. There were no genes showing significant differences in expression when the group with BRCA1 loss through epigenetic silencing was compared to either of the other two groups.

Conclusions

In this series of 28 high-grade serous carcinomas, gross genomic alteration characterized by aneuploidy did not correlate with BRCA1 status. In addition, the gene expression profiles of the tumors showed negligible differences between the three defined groups based on BRCA1 status. This suggests that all ovarian high-grade serous carcinomas arise through oncogenic mechanisms that result in chromosomal instability, irrespective of BRCA status; the molecular abnormalities underlying this in the BRCA intact tumors remains unknown.
Cytochrome 450 1B1 (CYP1B1) polymorphisms associated with response to docetaxel in Castration-Resistant Prostate Cancer (CRPC) patients
Authors: Pastina Ilaria , Giovannetti Elisa , Chioni Aldo , Sissung Tristan M , Crea Francesco , Orlandini Cinzia , Price Douglas K , Cianci Claudia , Figg William D , Ricci Sergio , Danesi Romano
Published: September 2010

Background

The selection of patients according to key genetic characteristics may help to tailor chemotherapy and optimize the treatment in Castration-Resistant Prostate Cancer (CRPC) patients. Functional polymorphisms within thecytochrome P450 1B1(CYP1B1) gene have been associated with alterations in enzymatic expression and activity and may change sensitivity to the widely used docetaxel regimen.

Methods

CYP1B1genotyping was performed on blood samples of 60 CRPC patients treated with docetaxel, using TaqMan probes-based assays. Association betweenCYP1B1-142C>G (leading to the 48ArgGly transition), 4326C>G (432LeuVal), and 4390A>G (453AsnSer) polymorphisms and treatment response, progression-free-survival (PFS) and overall-survival (OS) was estimated using Pearson χ2test, Kaplan-Meier curves and Log-rank test.

Results

Patients carrying theCYP1B1-432ValVal genotype experienced a significantly lower response-rate (P = 0.014), shorter progression-free-survival (P = 0.032) and overall-survival (P < 0.001). Multivariate analyses and correction for multiple comparisons confirmed its prognostic significance for OS. No significant associations were found among other polymorphisms and both response and clinical outcome.

Conclusions

CYP1B1-4326C>G (432LeuVal) polymorphism emerged as possible predictive marker of response and clinical outcome to docetaxel in CRPC patients and may represent a potential new tool for treatment optimization. Larger prospective trials are warranted to validate these findings, which might be applied to the future practice of CRPC treatment.
Cytotoxic activity of Thai medicinal plants against human cholangiocarcinoma, laryngeal and hepatocarcinoma cells in vitro
Authors: Mahavorasirikul Wiratchanee , Viyanant Vithoon , Chaijaroenkul Wanna , Itharat Arunporn , Na-Bangchang Kesara
Published: September 2010

Background

Cholangiocarcinoma is a serious public health in Thailand with increasing incidence and mortality rates. The present study aimed to investigate cytotoxic activities of crude ethanol extracts of a total of 28 plants and 5 recipes used in Thai folklore medicine against human cholangiocarcinoma (CL-6), human laryngeal (Hep-2), and human hepatocarcinoma (HepG2) cell lines in vitro.

Methods

Cytotoxic activity of the plant extracts against the cancerous cell lines compared with normal cell line (renal epithelial cell: HRE) were assessed using MTT assay. 5-fluorouracil was used as a positive control. The IC50 (concentration that inhibits cell growth by 50%) and the selectivity index (SI) were calculated.

Results

The extracts from seven plant species (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, Ligusticum sinense, Mimusops elengi) and one folklore recipe (Pra-Sa-Prao-Yhai) exhibited promising activity against the cholangiocarcinoma CL-6 cell line with survival of less than 50% at the concentration of 50 μg/ml. Among these, the extracts from the five plants and one recipe (Atractylodes lancea, Kaempferia galangal, Zingiber officinal, Piper chaba, Mesua ferrea, and Pra-Sa-Prao-Yhai recipe) showed potent cytotoxic activity with mean IC50 values of 24.09, 37.36, 34.26, 40.74, 48.23 and 44.12 μg/ml, respectively. All possessed high activity against Hep-2 cell with mean IC50 ranging from 18.93 to 32.40 μg/ml. In contrast, activity against the hepatoma cell HepG2 varied markedly; mean IC50 ranged from 9.67 to 115.47 μg/ml. The only promising extract was from Zingiber officinal (IC50 = 9.67 μg/ml). The sensitivity of all the four cells to 5-FU also varied according to cell types, particularly with CL-6 cell (IC50 = 757 micromolar). The extract from Atractylodes lancea appears to be both the most potent and most selective against cholangiocarcinoma (IC50 = 24.09 μg/ml, SI = 8.6).

Conclusions

The ethanolic extracts from five plants and one folklore recipe showed potent cytotoxic activity against CL-6 cell. Sensitivity to other cancerous cell lines varied according to cell types and the hepatocarcinoma cell line. HepG2 appears to be the most resistant to the tested extracts.
Prediction model for high glycated hemoglobin concentration among ethnic Chinese in Taiwan
Authors: Chien Kuo-Liong , Lin Hung-Ju , Lee Bai-Chin , Hsu Hsiu-Ching , Chen Ming-Fong
Published: September 2010

Background

This study aimed to construct a prediction model to identify subjects with high glycated hemoglobin (HbA1c) levels by incorporating anthropometric, lifestyle, clinical, and biochemical information in a large cross-sectional ethnic Chinese population in Taiwan from a health checkup center.

Methods

The prediction model was derived from multivariate logistic regression, and we evaluated the performance of the model in identifying the cases with high HbA1c levels (> = 7.0%). In total 17,773 participants (age > = 30 years) were recruited and 323 participants (1.8%) had high HbA1c levels. The study population was divided randomly into two parts, with 80% as the derivation data and 20% as the validation data.

Results

The point-based clinical model, including age (maximal 8 points), sex (1 point), family history (3 points), body mass index (2 points), waist circumference (4 points), and systolic blood pressure (3 points) reached an area under the receiver operating characteristic curve (AUC) of 0.723 (95% confidence interval, 0.677- 0.769) in the validation data. Adding biochemical measures such as triglycerides and HDL cholesterol improved the prediction power (AUC, 0.770 [0.723 - 0.817], P = < 0.001 compared with the clinical model). A cutoff point of 7 had a sensitivity of 0.76 to 0.96 and a specificity of 0.39 to 0.63 for the prediction model.

Conclusions

A prediction model was constructed for the prevalent risk of high HbA1c, which could be useful in identifying high risk subjects for diabetes among ethnic Chinese in Taiwan.
Non-viral eNOS gene delivery and transfection with stents for the treatment of restenosis
Authors: Brito Luis A , Chandrasekhar Saradha , Little Steven R , Amiji Mansoor M
Published: September 2010

Background

In this study, we have examined local non-viral gene delivery, transfection, and therapeutic efficacy of endothelial nitric oxide synthase (eNOS) encoding plasmid DNA administered using coated stents in a rabbit iliac artery restenosis model.

Methods

Lipopolyplexes (LPPs) with eNOS expressing plasmid DNA were immobilized on stainless steel stents using poly(D,L-lactide-co-glycolide) (PLGA) and type B gelatin coatings. The gene-eluting stents were implanted bilaterally in the denuded iliac arteries and eNOS transfection and therapeutic efficacy were examined 14 days after implantation.

Results

The results show that non-viral lipopolyplex-coated stents can efficiently tranfect eNOS locally in the arterial lumen assessed by PCR and ELISA. Human eNOS ELISA levels were significantly raised 24 hours after transfection compared to controls (125 pg eNOS compared to <50 pg for all controls including naked DNA). Local eNOS production suppressed smooth muscle cell proliferation and promoted re-endothelialization of the artery showing a significant reduction in restenosis of 1.75 neointima/media ratio for stents with lipoplexes encoding eNOS compared with 2.3 neointima/media ratio for stents with lipoplexes encosing an empty vector.

Conclusions

These results support the hypothesis that a potent non-viral gene vector encoding for eNOS coated onto a stent can inhibit restenosis through inhibition of smooth muscle cell growth and promotion of a healthy endothelium.
The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress
Authors: Arranz Alicia , Venihaki Maria , Mol Berber , Androulidaki Ariadne , Dermitzaki Erini , Rassouli Olga , Ripoll Jorge , Stathopoulos Efstathios N , Gomariz Rosa P , Margioris Andrew N , Tsatsanis Christos
Published: September 2010

Introduction

Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF) is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo.

Methods

For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis.

Results

Array analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this effect. Moreover, antalarmin suppressed neoangiogenesis in 4T1 tumors in vivo.

Conclusion

This is the first report demonstrating that peripheral CRF, at least in part, mediates the tumor-promoting effects of stress and implicates CRF in SMAD2 and β-catenin expression.
Left ventricular strain and strain rate by 2D speckle tracking in chronic thromboembolic pulmonary hypertension before and after pulmonary thromboendarterectomy
Authors: Olson Nicholas , Brown Jason P , Kahn Andrew M , Auger William R , Madani Michael M , Waltman Thomas J , Blanchard Daniel G
Published: September 2010

Background

Echocardiographic evaluation of left ventricular (LV) strain and strain rate (SR) by 2D speckle tracking may be useful tools to assess chronic thromboembolic pulmonary hypertension (CTEPH) severity as well as response to successful pulmonary thromboendarterectomy (PTE).

Methods

We evaluated 30 patients with CTEPH before and after PTE using 2D speckle tracking measurements of LV radial and circumferential strain and SR in the short axis, and correlated the data with right heart catheterization (RHC).

Results

PTE resulted in a decrease in mean PA pressure (44 ± 15 to 29 ± 9 mmHg), decrease in PVR (950 ± 550 to 31 ± 160 [dyne-sec]/cm5), and an increase in cardiac output (3.9 ± 1.0 to 5.0 ± 1.0 L/min, p < 0.001 for all). Circumferential and posterior wall radial strain changed by -11% and +15% respectively (p < 0.001 for both). Circumferential SR and posterior wall radial SR changed by -7% and 6% after PTE. While the increase in posterior wall SR with PTE reached statistical significance (p = 0.04) circumferential SR did not (p = 0.07). In addition, septal radial strain and SR did not change significantly after PTE (p = 0.1 and 0.8 respectively). Linear regression analyses of circumferential and posterior wall radial strain and SR revealed little correlation between strain/SR measurements and PVR, mean PA pressure, or cardiac output. However, change in circumferential strain and change in posterior wall radial strain correlated moderately well with changes in PVR, mean PA pressure and cardiac output (r = 0.69, 0.76, and 0.51 for circumferential strain [p < 0.001 for all] and r = 0.7, 0.7, 0.45 for posterior wall radial strain [p = 0.001, 0.001, and 0.02, respectively]).

Conclusions

LV circumferential and posterior wall radial strain change after relief of pulmonary arterial obstruction in patients with CTEPH, and these improvements occur rapidly. These changes in LV strain may reflect effects from improved LV diastolic filling, and may be useful non-invasive markers of successful PTE.
Do patients think cannabis causes schizophrenia? - A qualitative study on the causal beliefs of cannabis using patients with schizophrenia
Authors: Buadze Anna , Stohler Rudolf , Schulze Beate , Schaub Michael , Liebrenz Michael
Published: September 2010

Background

There has been a considerable amount of debate among the research community whether cannabis use may cause schizophrenia and whether cannabis use of patients with schizophrenia is associated with earlier and more frequent relapses. Considering that studies exploring patients' view on controversial topics have contributed to our understanding of important clinical issues, it is surprising how little these views have been explored to add to our understanding of the link between cannabis and psychosis. The present study was designed to elucidate whether patients with schizophrenia who use cannabis believe that its use has caused their schizophrenia and to explore these patients other beliefs and perceptions about the effects of the drug.

Methods

We recruited ten consecutive patients fulfilling criteria for paranoid schizophrenia and for a harmful use of/dependence from cannabis (ICD-10 F20.0 + F12.1 or F12.2) from the in- and outpatient clinic of the Psychiatric University Hospital Zurich. They were interviewed using qualitative methodology. Furthermore, information on amount, frequency, and effects of use was obtained. A grounded theory approach to data analysis was taken to evaluate findings.

Results

None of the patients described a causal link between the use of cannabis and their schizophrenia. Disease models included upbringing under difficult circumstances (5) or use of substances other than cannabis (e. g. hallucinogens, 3). Two patients gave other reasons. Four patients considered cannabis a therapeutic aid and reported that positive effects (reduction of anxiety and tension) prevailed over its possible disadvantages (exacerbation of positive symptoms).

Conclusions

Patients with schizophrenia did not establish a causal link between schizophrenia and the use of cannabis. We suggest that clinicians consider our findings in their work with patients suffering from these co-occurring disorders. Withholding treatment or excluding patients from certain treatment settings like day-care facilities or in patient care because of their use of cannabis, may cause additional harm to this already heavily burdened patient group.
Violence toward physicians in emergency departments of Morocco: prevalence, predictive factors, and psychological impact
Authors: Belayachi Jihane , Berrechid Kamal , Amlaiky Fatiha , Zekraoui Aicha , Abouqal Redouane
Published: September 2010

Introduction

Anyone working in the hospital may become a victim of violence. The effects of violence can range in intensity and include the following: minor physical injuries, serious physical injuries, temporary or permanent physical disability, psychological trauma, and death. The aim of this study was to determine the frequency of exposure, characteristics, and psychological impact of violence toward hospital-based emergency physicians in Morocco.

Methods

This was a survey including emergency physicians who ensured emergency service during the last fortnight. The variables studied were those related to the victim (age and gender), and those related to aggression: assaulter gender, number, time, reason (delay of consultation and/or care, acute drunkenness, neuropsychiatric disease), and type (verbal abuse, verbal threat and/or physical assault). After the questionnaire was completed, State-Trait Anxiety Inventory (STAI) of Spielberg was applied to all participants.

Results

A total of 60 physicians have achieved permanence in emergency department during the 15 days preceding the questionnaire response. The mean age was 24 ± 1 year and 57% were male. A total of 42 (70%) had been exposed to violence. The violence occurred at night n = 16 (27%), afternoon n = 13 (22%), evening n = 7 (12%) and morning n = 6 (10%). Reasons for violence were: the delay of consultation or care in n = 31 (52%) cases, acute drunkenness in n = 10 (17%) cases and neuropsychiatric disease in n = 3 (5%) cases. Twenty eight (47%) participants stated that they experienced verbal abuse, n = 18 (30%) verbal threat and n = 5 (8.3%) physical assault. Exposure to some form of violence was related to a higher median [interquartile range, IQR] state anxiety point (SAP); (51 [46-59] vs 39 [34-46]; P < 0,001), and trait anxiety point (TAP) (48 [41-55] vs 40,5 [38-53]; P = 0,01).

Conclusions

This study revealed a high prevalence (70%) of violence toward doctors in Morocco emergency departments. The exposure of physicians to some form of violence is greater among doctors with anxiety trait and was related to significant degree of anxiety state.
Use of serum squamous cell carcinoma antigen for follow-up monitoring of cervical cancer patients who were treated by concurrent chemoradiotherapy
Authors: Yoon Sang Min , Shin Kyung Hwan , Kim Joo-Young , Seo Sang Soo , Park Sang-Yoon , Moon Sung Ho , Cho Kwan Ho
Published: September 2010

Background

To investigate the significance of monitoring the levels of the serum squamous cell carcinoma antigen (SCC-Ag) for the detection of recurrent disease in patients with cervical cancer treated by concurrent chemoradiotherapy.

Methods

The records of 112 patients with cervical cancer were reviewed. Serum SCC-Ag levels were measured at regular follow-up visits. A SCC-Ag level of 2 ng/mL was considered the upper limit of normal. Biochemical failure was defined as two consecutively increasing SCC-Ag values above normal. Recurrent disease was confirmed by histologic and radiographic studies.

Results

Eighteen patients (16%) developed recurrent disease. Sixteen patients had initially elevated SCC-Ag, post-treatment normalization of SCC-Ag, and tumor recurrence. The SCC-Ag difference (ΔSCC-Ag), defined as the difference between the last value after two consecutively increases above normal and the value immediately before the elevation, had good clinical performance in predicting cancer recurrence. The cutoff value of ΔSCC-Ag was 0.95 ng/mL.

Conclusions

SCC-Ag is a relatively good method for the detection of disease recurrence in patients with cervical cancer who were treated by concurrent chemoradiotherapy.
Buccal mucosa carcinoma: surgical margin less than 3 mm, not 5 mm, predicts locoregional recurrence
Authors: Chiou Wen-Yen , Lin Hon-Yi , Hsu Feng-Chun , Lee Moon-Sing , Ho Hsu-Chueh , Su Yu-Chieh , Lee Ching-Chih , Hsieh Chen-Hsi , Wang Yao-Ching , Hung Shih-Kai
Published: September 2010

Background

Most treatment failure of buccal mucosal cancer post surgery is locoregional recurrence. We tried to figure out how close the surgical margin being unsafe and needed further adjuvant treatment.

Methods

Between August 2000 and June 2008, a total of 110 patients with buccal mucosa carcinoma (25 with stage I, 31 with stage II, 11 with stage III, and 43 with Stage IV classified according to the American Joint Committee on Cancer 6th edition) were treated with surgery alone (n = 32), surgery plus postoperative radiotherapy (n = 38) or surgery plus adjuvant concurrent chemoradiotherapy (n = 40).

Main outcome measures: The primary endpoint was locoregional disease control.

Results

The median follow-up time at analysis was 25 months (range, 4-104 months). The 3-year locoregional control rates were significantly different when a 3-mm surgical margin (≤3 versus >3 mm, 71% versus 95%, p = 0.04) but not a 5-mm margin (75% versus 92%, p = 0.22) was used as the cut-off level. We also found a quantitative correlation between surgical margin and locoregional failure (hazard ratio, 2.16; 95% confidence interval, 1.14 - 4.11; p = 0.019). Multivariate analysis identified pN classification and surgical margin as independent factors affecting disease-free survival and locoregional control.

Conclusions

Narrow surgical margin ≤3 mm, but not 5 mm, is associated with high risk for locoregional recurrence of buccal mucosa carcinoma. More aggressive treatment after surgery is suggested.
Identification of sequence polymorphism in the D-Loop region of mitochondrial DNA as a risk factor for hepatocellular carcinoma with distinct etiology
Authors: Zhang Ruixing , Zhang Fengbin , Wang Cuiju , Wang Shunxiang , Shiao Yih-Horng , Guo Zhanjun
Published: September 2010

Background

Hepatocellular carcinoma (HCC) is frequently preceded by hepatitis virus infection or alcohol abuse. Genetic backgrounds may increase susceptibility to HCC from these exposures.

Methods

Mitochondrial DNA (mtDNA) of peripheral blood, tumor, and/or adjacent non-tumor tissue from 49 hepatitis B virus-related and 11 alcohol-related HCC patients, and from 38 controls without HCC were examined for single nucleotide polymorphisms (SNPs) and mutations in the D-Loop region.

Results

Single nucleotide polymorphisms (SNPs) in the D-loop region of mt DNA were examined in HCC patients. Individual SNPs, namely the 16266C/T, 16293A/G, 16299A/G, 16303G/A, 242C/T, 368A/G, and 462C/T minor alleles, were associated with increased risk for alcohol- HCC, and the 523A/del was associated with increased risks of both HCC types. The mitochondrial haplotypes under the M haplogroup with a defining 489C polymorphism were detected in 27 (55.1%) of HBV-HCCand 8 (72.7%) of alcohol- HCC patients, and in 15 (39.5%) of controls. Frequencies of the 489T/152T, 489T/523A, and 489T/525C haplotypes were significantly reduced in HBV-HCC patients compared with controls. In contrast, the haplotypes of 489C with 152T, 249A, 309C, 523Del, or 525Del associated significantly with increase of alcohol-HCC risk. Mutations in the D-Loop region were detected in 5 adjacent non-tumor tissues and increased in cancer stage (21 of 49 HBV-HCC and 4 of 11 alcohol- HCC, p < 0.002).

Conclusions

In sum, mitochondrial haplotypes may differentially predispose patients to HBV-HCC and alcohol-HCC. Mutations of the mitochondrial D-Loop sequence may relate to HCC development.