bluuebunny/crossref_metadata_2025 huggingface dataset:
Active research towards the addressal of HIV/AIDS in the informal economy in Zambia
Authors: McKay Veronica I. , Romm Norma R. A.
Published: May 2008

In this article we offer an account of research undertaken for the International Labour Organization (on behalf of the National Aids Council in Zambia) in relation to HIV/AIDS and the informal economy in Zambia. We concentrate on how we tried to operate in terms of a conscious recognition of (and acceptance of responsibility for) our complicity as inquirers (together with others) in the development of the unfolding situations being explored. We indicate why we define as `active research' the approach adopted, and how we see this as related to the broader category of `action research'. We suggest that this kind of approach may be helpful for others wishing to engage in development programmes broadly understood and intended to support people's efforts to develop viable ways of knowing-and-living.
Research for change
Authors: Buskens Ineke , Earl Sarah
Published: May 2008

Although emancipatory action research has been practised for decades and continues to evolve, the method can benefit from the support of fresh approaches. Outcome mapping is an innovative planning, monitoring, and evaluation methodology recently conceived by Canada's International Development Research Centre in partnership with others. This article sets out the ways the two approaches complement one another on the level of theory, and describes how they have worked together in the everyday management of a specific initiative: the Infant Feeding Research Project, which aims to reduce the rate of paediatric HIV/AIDS in southern Africa through enhancing the effectiveness of infant feeding counselling.
Action research and social development in China
Authors: Sung-Chan Pauline , Yuen-Tsang Angelina , Yadama Gautam N. , Sze Alan
Published: May 2008

This article argues that the usefulness of action research hinges on a heightened sensitivity towards its relevance and irrelevance to social, economic and cultural environments in which the professional action researchers conduct their research. Its contribution to transforming social situations depends on how well the researchers can bring the different stakeholders of the local community together to learn about themselves and each other, and identify and find ways to address the implicit barriers to the effective use of action research. We also argue that it is this contribution that distinguishes action research from other approaches of social development in China. We draw from the lessons learned during one of our action research projects conducted in China with a focus on seeking effective strategies in dealing with the unemployment problem of middle-aged women workers. The researchers played the role of change agents to encourage participatory negotiation between the local officials and the women.
Generating the power for development through sustained dialogue
Authors: Nemeroff Teddy
Published: May 2008

This article describes a project to promote development in a rural area of the KwaZulu Natal Province of South Africa. Using a methodology called sustained dialogue, this project engaged a cross-section of leaders from several villages to reflect on past development efforts, design and implement new projects, and then evaluate their success. This project shows that a key contribution that action research skills can make is helping communities to see development not as a destination characterized by material conditions, but rather as a process of learning that results in economic advances. At the same time, this article highlights the political and conflict challenges inherent to community development. In responding to these challenges, this article argues for a focus on changing relationships and presents sustained dialogue's five elements of relationship as a tool for doing so.
Over the rainbow
Authors: Mehta Lyla
Published: May 2008

This article deals with different methodological enquiries in researching citizenship and marginality in a developing context. It is based on reflections emerging from a five-year collaborative international research programme that focused on enhancing the efforts of the poor and marginalized groups to define and claim their rights and make citizenship matter. The article deals with the politics and dilemmas inherent in the different methodological stances and positions of action research and other sister approaches towards the question of citizenship. Reflections from the researchers are interspersed with theoretical issues to highlight the messiness of the research process. The article argues for the need to challenge dominant framings in development, to be more modest about and redefine what we mean by policy influence and research impacts, to be more process-oriented and reflexive and to engage more strongly in a pedagogy of the powerful.
Treatment of Sexual Offenders With Psychopathic Traits
Authors: Abracen Jeffrey , Looman Jan , Langton Calvin M.
Published: May 2008

This article provides a review of recent literature related to the treatment of psychopathy in forensic settings, with particular focus on studies with sexual offenders. The lack of empirical support for the position that psychopaths are untreatable is noted, and data suggesting optimism is discussed. Research demonstrating an interaction between psychopathy and substance abuse and between psychopathy and sexual deviance is also presented. Both substance abuse disorders and inappropriate arousal are frequently encountered in high-risk groups of sexual offenders. These topics are of relevance, in that the question of whether treatment is beneficial with high-risk sexual offenders, including those who are psychopathic, cannot be answered unless groups presenting with typical concurrent disorders (paraphilias, substance abuse, dependence) are discussed. It is argued that, although the evidence is still preliminary, there is reason for optimism with reference to whether psychopathic sexual offenders are responsive to treatment, including offenders presenting with concurrent disorders.
Assessing the Economic Impact of College Football Games on Local Economies
Authors: Baade Robert A. , Baumann Robert W. , Matheson Victor A.
Published: May 2008

This article provides an empirical examination of the economic impact of spectator sports on local economies. Confirming the results of other ex post analyses of sports in general, this article finds no statistically significant evidence that college football games in particular contribute positively to a host's economy. Our analysis from 1970 to 2004 of 63 metropolitan areas that played host to big-time college football programs finds that neither the number of home games played, the winning percentage of the local team, nor winning a national championship has a discernable impact on either employment or personal income in the cities where the teams play. An examination of a subset of 42 smaller college towns finds that winning seasons actually reduce the growth rate of per capita personal income. Although successful college football teams may bring fame to their home towns, fortune appears to be a bit more elusive.
Determining Economic Contributions in a Recreational Industry
Authors: Watson Philip , Davies Steve , Thilmany Dawn
Published: May 2008

The estimation of economic contributions, activity, and impacts from industries, businesses, and events is a cornerstone of the regional economic development field, yet the approaches used to conduct such studies are rarely discussed in detail. Although Impact Analysis for Planning (IMPLAN) input—output economic modeling software and other regional models have become the standard, many industries, such as golf, are not represented in baseline data and therefore the model must be customized to facilitate regional analysis of these specific sectors. Using primary data collection techniques of both golf course operators and golfers in Colorado, both the backward linkages of the golf course industry and the stemming-from effects of the golf-related tourism expenditures were estimated and incorporated into the IMPLAN regional input—output modeling system. The customized IMPLAN model found the contribution of the golf industry's economic activity from both golf course operations and tourist expenditures to be $1.6 billion.
Validity of Functional Behavior Assessment Within a Response to Intervention Framework
Authors: McIntosh Kent , Brown Jacqueline A. , Borgmeier Christopher J.
Published: May 2008

This article discusses the evidence for intervention validity of Functional Behavior Assessment (FBA) in designing support for students with intensive behavioral needs. Since its inclusion into the Individuals With Disabilities Education Act nearly a decade ago, FBA has been the subject of significant research investigating its use and applicability to school-based behavior support. This research, specifically designed to address the question of intervention validity, provides solid evidence of the treatment utility of FBA for behavior support, demonstrating the critical need to use a function-based approach for improved behavior outcomes. The authors present recommendations for research-validated practice in school settings and identify a research agenda to move the field forward in light of the current focus on response to intervention.
A Response-to-Intervention Approach to Decreasing Early Literacy Differences in First Graders From Different Socioeconomic Backgrounds
Authors: Hagans Kristi S.
Published: May 2008

Federal legislation mandates that local education agencies provide quality, evidence-based supplemental educational services to struggling learners. Nowhere is this more salient than in underperforming schools serving children from low-income backgrounds who are at risk for developing learning problems. The study described in this article investigated the intervention validity of two measurement tasks from the Dynamic Indicators of Basic Early Literacy Skills (DIBELS) on the acquisition of early literacy skills of 75 first graders from low-income backgrounds. Results indicate that the DIBELS measures effectively modeled expected student growth and informed instructional planning that ultimately led to increased student outcomes.
Residual vein thrombosis to establish duration of anticoagulation after a first episode of deep vein thrombosis: the Duration of Anticoagulation based on Compression UltraSonography (DACUS) study
Authors: Siragusa Sergio , Malato Alessandra , Anastasio Raffaela , Cigna Valeria , Milio Glauco , Amato Corrado , Bellisi Mario , Attanzio Maria Teresa , Cormaci Oreste , Pellegrino Massimo , Dolce Alberto , Casuccio Alessandra , Bajardi Guido , Mariani Guglielmo
Published: May 2008

Residual vein thrombosis (RVT) indicates a prothrombotic state and is useful for evaluating the optimal duration of oral anticoagulant treatment (OAT). Patients with a first episode of deep vein thrombosis, treated with OAT for 3 months, were managed according to RVT findings. Those with RVT were randomized to either stop or continue anticoagulants for 9 additional months, whereas in those without RVT, OAT was stopped. Outcomes were recurrent venous thromboembolism and/or major bleeding. Residual thrombosis was detected in 180 (69.8%) of 258 patients; recurrent events occurred in 27.2% of those who discontinued (25/92; 15.2% person-years) and 19.3% of those who continued OAT (17/88; 10.1% person-years). The relative adjusted hazard ratio (HR) was 1.58 (95% confidence interval [CI], 0.85-2.93; P = .145). Of the 78 (30.2%) patients without RVT, only 1 (1.3%; 0.63% person-years) had a recurrence. The adjusted HR of patients with RVT versus those without was 24.9 (95% CI, 3.4-183.6; P = .002). One major bleeding event (1.1%; 0.53% person-years) occurred in patients who stopped and 2 occurred (2.3%; 1.1% person-years) in those who continued OAT. Absence of RVT identifies a group of patients at very low risk for recurrent thrombosis who can safely stop OAT. This trial was registered at http://www.ClinicalTrials.gov as no. NCT00438230.
Lymphoma depletion during CD20 immunotherapy in mice is mediated by macrophage FcγRI, FcγRIII, and FcγRIV
Authors: Minard-Colin Veronique , Xiu Yan , Poe Jonathan C. , Horikawa Mayuka , Magro Cynthia M. , Hamaguchi Yasuhito , Haas Karen M. , Tedder Thomas F.
Published: May 2008

Despite the demonstrated clinical efficacy of CD20 monoclonal antibody (mAb) for lymphoma therapy, the in vivo mechanisms of tumor depletion remain controversial and variable. To identify the molecular mechanisms responsible for lymphoma killing by CD20 mAb in a homologous system amenable to mechanistic studies and genetic manipulation, a mouse lymphoma model was developed using primary tumor cells from a C57BL/6 Eμ-cMyc transgenic mouse and mouse antimouse CD20 mAbs. CD20 mAb treatment of syngeneic mice with adoptively transferred lymphomas prevented tumor development or significantly prolonged mouse survival depending on tumor volume, mAb dose, and treatment timing. Cooperative FcγRIV, FcγRIII, and FcγRI interactions mediated optimal lymphoma depletion by CD20 mAb in vivo, whereas clodronate-mediated depletion of macrophages eliminated the therapeutic benefit of CD20 mAb. Although CD20 mAbs activated complement in vitro and in vivo, normal and malignant B-cell depletion was induced through C1q- and C3-independent mechanisms. Thus, the ability of CD20 mAbs to deplete malignant B cells in vivo required FcγR-dependent use of the innate mononuclear cell immune system. These findings allow for mechanism-based predictions of the biologic outcome of CD20 mAb therapy and treatment optimization.
Human basophils activated by mast cell–derived IL-3 express retinaldehyde dehydrogenase-II and produce the immunoregulatory mediator retinoic acid
Authors: Spiegl Nicole , Didichenko Svetlana , McCaffery Peter , Langen Hanno , Dahinden Clemens A.
Published: May 2008

The vitamin A metabolite retinoic acid (RA) plays a fundamental role in cellular functions by activating nuclear receptors. Retinaldehyde dehydrogenase-II (RALDH2) creates localized RA gradients needed for proper embryonic development, but very little is known regarding its regulated expression in adults. Using a human ex vivo model of aller-gic inflammation by coincubating IgE receptor–activated mast cells (MCs) with blood basophils, we observed prominent induction of a protein that was identified as RALDH2 by mass spectroscopy. RALDH2 was selectively induced in basophils by MC-derived interleukin-3 (IL-3) involving PI3-kinase and NF-κB pathways. Importantly, neither constitutive nor inducible RALDH2 expression was detectable in any other human myeloid or lymphoid leukocyte, including dendritic cells. RA generated by RALDH2 in basophils modulates IL-3–induced gene expression in an autocrine manner, providing positive (CD25) as well as negative (granzyme B) regulation. It also acts in a paracrine fashion on T-helper cells promoting the expression of CD38 and α4/β7 integrins. Furthermore, RA derived from IL-3–activated basophils provides a novel mechanism of Th2 polarization. Thus, RA must be viewed as a tightly controlled basophil-derived mediator with a high potential for regulating diverse functions of immune and resident cells in allergic diseases and other Th2-type immune responses.
Syngeneic transplantation of hematopoietic stem cells that are genetically modified to express factor VIII in platelets restores hemostasis to hemophilia A mice with preexisting FVIII immunity
Authors: Shi Qizhen , Fahs Scot A. , Wilcox David A. , Kuether Erin L. , Morateck Patricia A. , Mareno Nicole , Weiler Hartmut , Montgomery Robert R.
Published: May 2008

Although genetic induction of factor VIII (FVIII) expression in platelets can restore hemostasis in hemophilia A mice, this approach has not been studied in the clinical setting of preexisting FVIII inhibitory antibodies to determine whether such antibodies would affect therapeutic engraftment. We generated a line of transgenic mice (2bF8) that express FVIII only in platelets using the platelet-specific αIIb promoter and bred this 2bF8 transgene into a FVIIInull background. Bone marrow (BM) from heterozygous 2bF8 transgenic (2bF8tg+/−) mice was transplanted into immunized FVIIInull mice after lethal or sublethal irradiation. After BM reconstitution, 85% of recipients survived tail clipping when the 1100-cGy (myeloablative) regimen was used, 85.7% of recipients survived when 660-cGy (nonmyeloablative) regimens were used, and 60% of recipients survived when the recipients were conditioned with 440 cGy. Our further studies showed that transplantation with 1% to 5% 2bF8tg+/− BM cells still improved hemostasis in hemophilia A mice with inhibitors. These results demonstrate that the presence of FVIII-specific immunity in recipients does not negate engraftment of 2bF8 genetically modified hematopoietic stem cells, and transplantation of these hematopoietic stem cells can efficiently restore hemostasis to hemophilic mice with preexisting inhibitory antibodies under either myeloablative or nonmyeloablative regimens.
Isolation, characterization and molecular cloning of Duplex-Specific Nuclease from the hepatopancreas of the Kamchatka crab
Authors: Anisimova Veronika E , Rebrikov Denis V , Shagin Dmitry A , Kozhemyako Valery B , Menzorova Natalia I , Staroverov Dmitry B , Ziganshin Rustam , Vagner Laura L , Rasskazov Valery A , Lukyanov Sergey A , Shcheglov Alex S
Published: May 2008

Background

Nucleases, which are key components of biologically diverse processes such as DNA replication, repair and recombination, antiviral defense, apoptosis and digestion, have revolutionized the field of molecular biology. Indeed many standard molecular strategies, including molecular cloning, studies of DNA-protein interactions, and analysis of nucleic acid structures, would be virtually impossible without these versatile enzymes. The discovery of nucleases with unique properties has often served as the basis for the development of modern molecular biology methods. Thus, the search for novel nucleases with potentially exploitable functions remains an important scientific undertaking.

Results

Using degenerative primers and the rapid amplification of cDNA ends (RACE) procedure, we cloned the Duplex-Specific Nuclease (DSN) gene from the hepatopancreas of the Kamchatka crab and determined its full primary structure. We also developed an effective method for purifying functional DSN from the crab hepatopancreas. The isolated enzyme was highly thermostable, exhibited a broad pH optimum (5.5 – 7.5) and required divalent cations for activity, with manganese and cobalt being especially effective. The enzyme was highly specific, cleaving double-stranded DNA or DNA in DNA-RNA hybrids, but not single-stranded DNA or single- or double-stranded RNA. Moreover, only DNA duplexes containing at least 9 base pairs were effectively cleaved by DSN; shorter DNA duplexes were left intact.

Conclusion

We describe a new DSN from Kamchatka crab hepatopancreas, determining its primary structure and developing a preparative method for its purification. We found that DSN had unique substrate specificity, cleaving only DNA duplexes longer than 8 base pairs, or DNA in DNA-RNA hybrids. Interestingly, the DSN primary structure is homologous to well-known Serratia-like non-specific nucleases structures, but the properties of DSN are distinct. The unique substrate specificity of DSN should prove valuable in certain molecular biology applications.
The metazoan history of the COE transcription factors. Selection of a variant HLH motif by mandatory inclusion of a duplicated exon in vertebrates
Authors: Daburon Virginie , Mella Sébastien , Plouhinec Jean-Louis , Mazan Sylvie , Crozatier Michèle , Vincent Alain
Published: May 2008

Background

The increasing number of available genomic sequences makes it now possible to study the evolutionary history of specific genes or gene families. Transcription factors (TFs) involved in regulation of gene-specific expression are key players in the evolution of metazoan development. The low complexity COE (Collier/Olfactory-1/Early B-Cell Factor) family of transcription factors constitutes a well-suited paradigm for studying evolution of TF structure and function, including the specific question of protein modularity. Here, we compare the structure of coe genes within the metazoan kingdom and report on the mechanism behind a vertebrate-specific exon duplication.

Results

COE proteins display a modular organisation, with three highly conserved domains : a COE-specific DNA-binding domain (DBD), an Immunoglobulin/Plexin/transcription (IPT) domain and an atypical Helix-Loop-Helix (HLH) motif. Comparison of the splice structure of coe genes between cnidariae and bilateriae shows that the ancestral COE DBD was built from 7 separate exons, with no evidence for exon shuffling with other metazoan gene families. It also confirms the presence of an ancestral H1LH2 motif present in all COE proteins which partly overlaps the repeated H2d-H2a motif first identified in rodent EBF. Electrophoretic Mobility Shift Assays show that formation of COE dimers is mediated by this ancestral motif. The H2d-H2a α-helical repetition appears to be a vertebrate characteristic that originated from a tandem exon duplication having taken place prior to the splitting between gnathostomes and cyclostomes. We put-forward a two-step model for the inclusion of this exon in the vertebrate transcripts.

Conclusion

Three main features in the history of the coe gene family can be inferred from these analyses: (i) each conserved domain of the ancestral coe gene was built from multiple exons and the same scattered structure has been maintained throughout metazoan evolution. (ii) There exists a single coe gene copy per metazoan genome except in vertebrates. The H2a-H2d duplication that is specific to vertebrate proteins provides an example of a novel vertebrate characteristic, which may have been fixed early in the gnathostome lineage. (iii) This duplication provides an interesting example of counter-selection of alternative splicing.
Predicting prognosis using molecular profiling in estrogen receptor-positive breast cancer treated with tamoxifen
Authors: Loi Sherene , Haibe-Kains Benjamin , Desmedt Christine , Wirapati Pratyaksha , Lallemand Françoise , Tutt Andrew M , Gillet Cheryl , Ellis Paul , Ryder Kenneth , Reid James F , Daidone Maria G , Pierotti Marco A , Berns Els MJJ , Jansen Maurice PHM , Foekens John A , Delorenzi Mauro , Bontempi Gianluca , Piccart Martine J , Sotiriou Christos
Published: May 2008

Background

Estrogen receptor positive (ER+) breast cancers (BC) are heterogeneous with regard to their clinical behavior and response to therapies. The ER is currently the best predictor of response to the anti-estrogen agent tamoxifen, yet up to 30–40% of ER+BC will relapse despite tamoxifen treatment. New prognostic biomarkers and further biological understanding of tamoxifen resistance are required. We used gene expression profiling to develop an outcome-based predictor using a training set of 255 ER+ BC samples from women treated with adjuvant tamoxifen monotherapy. We used clusters of highly correlated genes to develop our predictor to facilitate both signature stability and biological interpretation. Independent validation was performed using 362 tamoxifen-treated ER+ BC samples obtained from multiple institutions and treated with tamoxifen only in the adjuvant and metastatic settings.

Results

We developed a gene classifier consisting of 181 genes belonging to 13 biological clusters. In the independent set of adjuvantly-treated samples, it was able to define two distinct prognostic groups (HR 2.01 95%CI: 1.29–3.13; p = 0.002). Six of the 13 gene clusters represented pathways involved in cell cycle and proliferation. In 112 metastatic breast cancer patients treated with tamoxifen, one of the classifier components suggesting a cellular inflammatory mechanism was significantly predictive of response.

Conclusion

We have developed a gene classifier that can predict clinical outcome in tamoxifen-treated ER+ BC patients. Whilst our study emphasizes the important role of proliferation genes in prognosis, our approach proposes other genes and pathways that may elucidate further mechanisms that influence clinical outcome and prediction of response to tamoxifen.
Gene expression analysis of embryonic stem cells expressing VE-cadherin (CD144) during endothelial differentiation
Authors: Nikolova-Krstevski Vesna , Bhasin Manoj , Otu Hasan H , Libermann Towia , Oettgen Peter
Published: May 2008

Background

Endothelial differentiation occurs during normal vascular development in the developing embryo. This process is recapitulated in the adult when endothelial progenitor cells are generated in the bone marrow and can contribute to vascular repair or angiogenesis at sites of vascular injury or ischemia. The molecular mechanisms of endothelial differentiation remain incompletely understood. Novel approaches are needed to identify the factors that regulate endothelial differentiation.

Methods

Mouse embryonic stem (ES) cells were used to further define the molecular mechanisms of endothelial differentiation. By flow cytometry a population of VEGF-R2 positive cells was identified as early as 2.5 days after differentiation of ES cells, and a subset of VEGF-R2+ cells, that were CD41 positive at 3.5 days. A separate population of VEGF-R2+ stem cells expressing the endothelial-specific marker CD144 (VE-cadherin) was also identified at this same time point. Channels lined by VE-cadherin positive cells developed within the embryoid bodies (EBs) formed by differentiating ES cells. VE-cadherin and CD41 expressing cells differentiate in close proximity to each other within the EBs, supporting the concept of a common origin for cells of hematopoietic and endothelial lineages.

Results

Microarray analysis of >45,000 transcripts was performed on RNA obtained from cells expressing VEGF-R2+, CD41+, and CD144+ and VEGF-R2-, CD41-, and CD144-. All microarray experiments were performed in duplicate using RNA obtained from independent experiments, for each subset of cells. Expression profiling confirmed the role of several genes involved in hematopoiesis, and identified several putative genes involved in endothelial differentiation.

Conclusion

The isolation of CD144+ cells during ES cell differentiation from embryoid bodies provides an excellent model system and method for identifying genes that are expressed during endothelial differentiation and that are distinct from hematopoiesis.
The role of Toll-like receptor-4 in pertussis vaccine-induced immunity
Authors: Banus Sander , Stenger Rachel M , Gremmer Eric R , Dormans Jan AMA , Mooi Frits R , Kimman Tjeerd G , Vandebriel Rob J
Published: May 2008

Background

The gram-negative bacterium Bordetella pertussis is an important causative agent of pertussis, an infectious disease of the respiratory tract. After introduction of whole-cell vaccines (wP) in the 1950's, pertussis incidence has decreased significantly. Because wP were found to be reactogenic, in most developed countries they have been replaced by acellular vaccines (aP). We have previously shown a role for Toll-like receptor 4 (Tlr4) in pertussis-infected mice and the pertussis toxin (Ptx)-IgG response in wP-vaccinated children, raising the issue of the relative importance of Tlr4 in wP vaccination of mice. Here we analyze the effects of wP and aP vaccination and B. pertussis challenge, in Tlr4-deficient C3H/HeJ and wild-type C3H/HeOuJ mice. aP consists of Ptx, filamentous hemagglutinin (FHA), and pertactin (Prn).

Results

We show an important role of Tlr4 in wP and (to a lesser extent) aP vaccination, induction of Th1 and Th17 cells by wP but not aP vaccination, and induction of Th17 cells by infection, confirming data by Higgins et al. (J Immunol 2006, 177: 7980–9). Furthermore, in Tlr4-deficient mice, compared to wild-type controls (i) after vaccination only, Ptx-IgG (that was induced by aP but not wP vaccination), FHA-IgG, and Prn-IgG levels were similar, (ii) after infection (only), lung IL-1α and IL-1β expression were lower, (iii) after wP vaccination and challenge, Prn-IgG level and lung IL-5 expression were higher, while lung IL-1β, TNF-α, IFN-γ, IL-17, and IL-23 expression were lower, and lung pathology was absent, and (iv) after aP vaccination and challenge, Prn-IgG level and lung IL-5 expression were higher, while Ptx-IgG level was lower.

Conclusion

Tlr4 does not influence the humoral response to vaccination (without challenge), plays an important role in natural immunity, wP and aP efficacy, and induction of Th1 and Th17 responses, is critical for lung pathology and enhances pro-inflammatory cytokine production after wP vaccination and challenge, and diminishes Th2 responses after both wP and aP vaccination and challenge. wP vaccination does not induce Ptx-IgG. A role for LPS in the efficacy of wP underlines the usefulness of LPS analogs to improve bacterial subunit vaccines such as aP.
Presence of qnr gene in Escherichia coli and Klebsiella pneumoniae resistant to ciprofloxacin isolated from pediatric patients in China
Authors: Wang Aihua , Yang Yonghong , Lu Quan , Wang Yi , Chen Yuan , Deng Li , Ding Hui , Deng Qiulian , Zhang Hong , Wang Chuanqing , Liu Lan , Xu Xiwei , Wang Li , Shen Xuzhuang
Published: May 2008

Background

Quinolone resistance in Enterobacteriaceae results mainly from mutations in type II DNA topoisomerase genes and/or changes in the expression of outer membrane and efflux pumps. Several recent studies have indicated that plasmid-mediated resistance mechanisms also play a significant role in fluoroquinolone resistance, and its prevalence is increasing worldwide. In China, the presence of the qnr gene in the clinical isolates of Enterobacteriaceae has been reported, but this transmissible quinolone resistance gene has not been detected in strains isolated singly from pediatric patients. Because quinolones associated with a variety of adverse side effects on children, they are not authorized for pediatric use. This study therefore aimed to investigate the presence of the qnr gene in clinical isolates of E. coli and K. pneumoniae from pediatric patients in China.

Methods

A total 213 of non-repetitive clinical isolates resistant to ciprofloxacin from E. coli and K. pneumoniae were collected from hospitalized patients at five children's hospital in Beijing, Shanghai, Guangzhou, and Chongqing. The isolates were screened for the plasmid-mediated quinolone resistance genes of qnrA, qnrB, and qnrS by PCR. Transferability was examined by conjugation with the sodium azide-resistant E. coli J53. All qnr-positive were analyzed for clonality by enterobacterial repetitive intergenic consensus (ERIC)-PCR.

Results

The study found that 19 ciprofloxacin-resistant clinical isolates of E. coli and K. pneumoniae were positive for the qnr gene, and most of the qnr positive strains were ESBL producers. Conjugation experiments showed that quinolone resitance could be transferred to recipients. Apart from this, different DNA banding patterns were obtained by ERIC-PCR from positive strains, which means that most of them were not clonally related.

Conclusion

This report on transferable fluoroquinolone resistance due to the qnr gene among E. coli and K. pneumoniae strains indicated that plasmid-mediated quinolone resistance has emerged in pediatric patients in China.
A novel de novo mutation in the serine-threonine kinase STK11 gene in a Korean patient with Peutz-Jeghers syndrome
Authors: Yoo Jong-Ha , Yoo Jee-Hyoung , Choi Yoon-Jung , Kang Jung-Gu , Sun Young-Kyu , Ki Chang-Seok , Lee Kyung-A , Choi Jong-Rak
Published: May 2008

Background

Peutz-Jeghers syndrome (PJS) is an unusual autosomal dominant disorder characterized by mucocutaneous pigmentation and multiple gastrointestinal hamartomatous polyps. Patients with PJS are at an increased risk of developing multi-organ cancer, most frequently those involving the gastrointestinal tract. Germline mutation of the STK11 gene, which encodes a serine-threonine kinase, is responsible for PJS.

Methods

Using DNA samples obtained from the patient and his family members, we sequenced nine exons and flanking intron regions of the STK11 gene using polymerase chain reaction (PCR) and direct sequencing.

Results

Sequencing of the STK11 gene in the proband of the family revealed a novel 1-base pair deletion of guanine (G) in exon 6 (c.826delG; Gly276AlafsX11). This mutation resulted in a premature termination at codon 286, predicting a partial loss of the kinase domain and complete loss of the C-terminal domain. We did not observe this mutation in both parents of the PJS patient. Therefore, it is considered a novel de novo mutation.

Conclusion

The results presented herein enlarge the spectrum of mutations of the STK11 gene by identifying a novel de novo mutation in a PJS patient and further support the hypothesis that STK11 mutations are disease-causing mutations for PJS with or without a positive family history.
The genetic susceptibility to type 2 diabetes may be modulated by obesity status: implications for association studies
Authors: Cauchi Stéphane , Nead Kevin T , Choquet Hélène , Horber Fritz , Potoczna Natascha , Balkau Beverley , Marre Michel , Charpentier Guillaume , Froguel Philippe , Meyre David
Published: May 2008

Background

Considering that a portion of the heterogeneity amongst previous replication studies may be due to a variable proportion of obese subjects in case-control designs, we assessed the association of genetic variants with type 2 diabetes (T2D) in large groups of obese and non-obese subjects.

Methods

We genotyped RETN, KCNJ11, HNF4A, HNF1A, GCK, SLC30A8, ENPP1, ADIPOQ, PPARG, and TCF7L2 polymorphisms in 1,283 normoglycemic (NG) and 1,581 T2D obese individuals as well as in 3,189 NG and 1,244 T2D non-obese subjects of European descent, allowing us to examine T2D risk over a wide range of BMI.

Results

Amongst non-obese individuals, we observed significant T2D associations with HNF1A I27L [odds ratio (OR) = 1.14, P = 0.04], GCK -30G>A (OR = 1.23, P = 0.01), SLC30A8 R325W (OR = 0.87, P = 0.04), and TCF7L2 rs7903146 (OR = 1.89, P = 4.5 × 10-23), and non-significant associations with PPARG Pro12Ala (OR = 0.85, P = 0.14), ADIPOQ -11,377C>G (OR = 1.00, P = 0.97) and ENPP1 K121Q (OR = 0.99, P = 0.94). In obese subjects, associations with T2D were detected with PPARG Pro12Ala (OR = 0.73, P = 0.004), ADIPOQ -11,377C>G (OR = 1.26, P = 0.02), ENPP1 K121Q (OR = 1.30, P = 0.003) and TCF7L2 rs7903146 (OR = 1.30, P = 1.1 × 10-4), and non-significant associations with HNF1A I27L (OR = 0.96, P = 0.53), GCK -30G>A (OR = 1.15, P = 0.12) and SLC30A8 R325W (OR = 0.95, P = 0.44). However, a genotypic heterogeneity was only found for TCF7L2 rs7903146 (P = 3.2 × 10-5) and ENPP1 K121Q (P = 0.02). No association with T2D was found for KCNJ11, RETN, and HNF4A polymorphisms in non-obese or in obese individuals.

Conclusion

Genetic variants modulating insulin action may have an increased effect on T2D susceptibility in the presence of obesity, whereas genetic variants acting on insulin secretion may have a greater impact on T2D susceptibility in non-obese individuals.
An economic analysis of email-based telemedicine: A cost minimisation study of two service models
Authors: Caffery Liam , Smith Anthony C , Scuffham Paul A
Published: May 2008

Background

Email-based telemedicine has been reported to be an efficient method of delivering online health services to patients at a distance and is often described as a low-cost form of telemedicine. The service may be low-cost if the healthcare organisation utilise their existing email infrastructure to provide their telemedicine service. Many healthcare organisations use commercial-off-the-shelf (COTS) email applications. COTS email applications are designed for peer-to-peer communication; hence, in situations where multiple clinicians need to be involved, COTS applications may be deficient in delivering telemedicine. Larger services often rely on different staff disciplines to run their service and telemedicine tools for supervisors, clinicians and administrative staff are not available in COTS applications. Hence, some organisations may choose to develop a purpose-written email application to support telemedicine. We have conducted a cost-minimisation analysis of two different service models for establishing and operating an email service. The first service model used a COTS email application and the second used a purpose-written telemedicine application.

Methods

The actual costs used in the analysis were from two organisations that originally ran their counselling service with a COTS email application and later implemented a purpose-written application. The purpose-written application automated a number of the tasks associated with running an email-based service. We calculated a threshold at which the higher initial costs for software development were offset by efficiency gains from automation. We also performed a sensitivity analysis to determine the effect of individual costs on the threshold.

Results

The cost of providing an email service at 1000 consultations per annum was $19,930 using a COTS email application and $31,925 using a purpose-written application. At 10,000 consultations per annum the cost of providing the service using COTS email software was $293,341 compared to $272,749 for the purpose-written application. The threshold was calculated at a workload of 5216 consultations per annum. When more than 5216 email consultations per annum are undertaken, the purpose-written application was cheaper than the COTS service model. The sensitivity analysis showed the threshold was most sensitive to changes in administrative staff salaries.

Conclusion

In the context of telemedicine, we have compared two different service models for email-based communication – purpose-written and COTS applications. Under the circumstances described in the paper, when workload exceeded 5216 email consultations per annum, there were savings made when a purpose-written email application was used. This analysis provides a useful economic model for organisations contemplating the use of an email-based telemedicine system.
Interactions between dendritic cells and CD4+ T cells during Plasmodium infection
Authors: Ocaña-Morgner Carlos , Wong Kurt A , Rodriguez Ana
Published: May 2008

Background

During infection, dendritic cells (DCs) encounter pathogenic microorganisms that can modulate their function and shape the T cell responses generated. During the process of T cell activation, DCs establish strong, long-lasting interactions with naïve T cells.

Methods

Using a mouse malaria model, the interactions of DCs and naïve CD4+T cells have been analysed.

Results

DCs, either incubatedin vitrowith infected erythrocytes or isolated from infected mice, are able to present exogenous antigens by MHC-II, but are not able to establish prolonged effective interactions with naïve CD4+T cells and do not induce T cell activation. It was also found that effective T cell activation of naïve CD4+T cells is impaired during latePlasmodium yoeliiinfection.

Conclusion

These data may provide a mechanism for the lack of effective adaptive immune responses induced by the Plasmodium parasite.
The potential impact of climate change on annual and seasonal mortality for three cities in Québec, Canada
Authors: Doyon Bernard , Bélanger Diane , Gosselin Pierre
Published: May 2008

Background

The impact of climate change and particularly increasing temperature on mortality has been examined for three cities in the province of Québec, Canada.

Methods

Generalized linear Poisson regression has been fitted to the total daily mortality for each city. Smooth parametric cubic splines of temperature and humidity have been used to do nonlinear modeling of these parameters. The model, to control for day of the week and for non-temperature seasonal factors, used a smooth function of time, including delayed effects. The model was then used to assess variation in mortality for simulated future temperatures obtained from an atmospheric General Circulation Model coupled with downscaling regression techniques. Two CO2 emission scenarios are considered (scenarios A2 and B2). Projections are made for future periods around year 2020 (2010–2039), 2050 (2040–2069) and 2080 (2070–2099).

Results

A significant association between mortality and current temperature has been found for the three cities. Under CO2 emission scenarios A2 and B2, the mortality model predicts a significant increase in mortality in the summertime, and a smaller, but significant decrease in the fall season. The slight variations in projected mortality for future winter and spring seasons were found to be not statistically significant. The variations in projected annual mortality are dominated by an increase in mortality in the summer, which is not balanced by the decrease in mortality in the fall and winter seasons. The summer increase and the annual mortality range respectively from about 2% and 0.5% for the 2020 period, to 10% and 3% for the years around 2080. The difference between the mortality variations projected with the A2 or B2 scenarios was not statistically significant.

Conclusion

For the three cities, the two CO2 emission scenarios considered led to an increase in annual mortality, which contrasts with most European countries, where the projected increase in summer mortality with respect to climate change is overbalanced by the decrease in winter mortality. This highlights the importance of place in such analyses. The method proposed here to establish these estimates is general and can also be applied to small cities, where mortality rates are relatively low (ex. two deaths/day).
DNA repair gene ERCC2 polymorphisms and associations with breast and ovarian cancer risk
Authors: Bernard-Gallon Dominique , Bosviel Rémy , Delort Laetitia , Fontana Luc , Chamoux Alain , Rabiau Nadège , Kwiatkowski Fabrice , Chalabi Nasséra , Satih Samir , Bignon Yves-Jean
Published: May 2008

Breast and ovarian cancers increased in the last decades. Except rare cases with a genetic predisposition and high penetrance, these pathologies are viewed as a polygenic disease. In this concept, association studies look for genetic variations such as polymorphisms in low penetrance genes,i.e. genes in interaction with environmental factors. DNA repair systems that protect the genome from deleterious endogenous and exogenous damages have been shown to have significantly reduced. In particular, enzymes of the nucleotide excision repair pathway are suspected to be implicated in cancer. In this study, 2 functional polymorphisms in a DNA repair geneERCC2were analyzed. The population included 911 breast cancer cases, 51 ovarian cancer cases and 1000 controls. The genotyping of 2 SNP (Single Nucleotide Polymorphism) was carried out on the population with the MGB (Minor Groove Binder) probe technique which consists of the use of the allelic discrimination with the Taqman®method. This study enabled us to show an increase in risk of breast cancer with no oral contraceptive users and with women exhibiting a waist-to-hip ratio (WHR) > 0.85 for Asn homozygous forERCC2 312.
Epigenetic changes within the promoter region of the HLA-G gene in ovarian tumors
Authors: Menendez Laura , Walker L DeEtte , Matyunina Lilya V , Totten Kimberly A , Benigno Benedict B , McDonald John F
Published: May 2008

Background

Previous findings have suggested that epigenetic-mediated HLA-G expression in tumor cells may be associated with resistance to host immunosurveillance. To explore the potential role of DNA methylation on HLA-G expression in ovarian cancer, we correlated differences in HLA-G expression with methylation changes within the HLA-G regulatory region in an ovarian cancer cell line treated with 5-aza-deoxycytidine (5-aza-dC) and in malignant and benign ovarian tumor samples and ovarian surface epithelial cells (OSE) isolated from patients with normal ovaries.

Results

A region containing an intact hypoxia response element (HRE) remained completely methylated in the cell line after treatment with 5-aza-dC and was completely methylated in all of the ovarian tumor (malignant and benign) samples examined, but only variably methylated in normal OSE samples. HLA-G expression was significantly increased in the 5-aza-dC treated cell line but no significant difference was detected between the tumor and OSE samples examined.

Conclusion

Since HRE is the binding site of a known repressor of HLA-G expression (HIF-1), we hypothesize that methylation of the region surrounding the HRE may help maintain the potential for expression of HLA-G in ovarian tumors. The fact that no correlation exists between methylation and HLA-G gene expression between ovarian tumor samples and OSE, suggests that changes in methylation may be necessary but not sufficient for HLA-G expression in ovarian cancer.
RETRACTED ARTICLE: Molecular analysis of the effects of Piroxicam and Cisplatin on mesothelioma cells growth and viability
Authors: Verdina Alessandra , Cardillo Irene , Nebbioso Angela , Galati Rossella , Menegozzo Simona , Altucci Lucia , Sacchi Ada , Baldi Alfonso
Published: May 2008

Nonsteroidal anti-inflammatory drugs (NSAIDs) have been proposed for prevention and treatment of a variety of human cancers. Piroxicam, in particular, has been recently shown to exert significant anti-tumoral activity in combination with cisplatin (CDDP) on mesothelioma cells. However, the mechanisms through which NSAIDs regulate the cell cycle as well as the signal pathways involved in the growth inhibition, remain unclear. In the present study, using two mesothelioma cell lines, MSTO-211H and NCI-H2452, we have investigated the influence of piroxicam alone and in association with CDDP on proliferation, cell cycle regulation and apoptosis. In both cell lines a significant effect on cell growth inhibition, respect to the control, was observed with all the drugs tested. Moreover, treatment with piroxicam or CDDP alone altered the cell cycle phase distribution as well as the expression of some cell cycle regulatory proteins in both cell lines. These effects were increased, even if in a not completely overlapping manner, after treatment with the association of piroxicam and CDDP. In particular, the two drugs in NCI cell line had a synergistic effect on apoptosis, probably through activation of caspase 8 and caspase 9, while the most evident targets among the cell cycle regulators were cyclin D1 and p21waf1. These results suggest that the association of piroxicam and CDDP specifically triggers cell cycle regulation and apoptosis in different mesothelioma cell lines and may hold promise in the treatment of mesothelioma.