bluuebunny/crossref_metadata_2025 huggingface dataset:
Looking through old lenses to understand the emerging new world order
Authors: Pillay Hitendra , Elliott Bob
Published: March 2005

English

There is increasing pressure on small island states to reconceptualize education policies, education management practices and curriculum to address the emerging issues caused by global economic, social and cultural changes. It has generated increasing demands on limited available resources which is further confounded by the often contradictory yet legitimate advice provided by international and local experts. This paper reflects on the changing expectations to provide a critical analysis of the challenges facing education planners in small developing countries. It challenges them to move beyond the stereotypical ways of thinking about education development while acknowledging the role played by previous educational development models.

French

Les petits états insulaires font l'objet de pressions croissantes pour reconceptualiser leur politique en matière d'éducation, leurs méthodes de gestion de la formation et leurs programmes et ce afin de pouvoir faire face aux problèmes croissants causés par les changements économiques, sociaux et culturels mondiaux. Cette situation a généré une demande croissante de ressources disponibles limitées, accentuée par les conseils, certes souvent contradictoires mais néanmoins légitimes, fournis par des experts internationaux et locaux. Cet article se penche sur ces perspectives d'évolution pour fournir une analyse critique des problèmes rencontrés par les personnes chargées de la planification de l'éducation dans les petits pays en voie de développement. Il les encourage à dépasser les réflexions stéréotypées sur le perfectionnement en matière d'éducation tout en reconnaissant l'importance des précédents modèles de perfectionnement de l'enseignement.

Spanish

Existe una presión cada vez mayor para que los estados insulares pequeños reconceptualicen sus políticas, sus prácticas de gestión y sus'currículos educativos para poder afrontar las cuestiones derivadas de los cambios económicos, sociales y culturales que se están produciendo en todo el mundo. Este fenómeno implica un aumento de las exigencias sobre los recursos disponibles, a lo cual se agrega una cierta confusión causada por los consejos de expertos locales e internacionales que, no obstante legítimos, a menudo se contradicen. Este trabajo aporta una reflexión sobre las expectativas planteadas, con el fin de ofrecer un análisis crítico de los desafíos a los que se enfrentan los encargados de la planificación educativa en pequeños estados insulares. Se propone hacerles pensar en el desarrollo de la educación más allá de los estereotipos imperantes, y reconocer la influencia de los modelos anteriores en las políticas actuales.
Factors affecting the likelihood that people with intellectual disabilities will gain employment
Authors: Rose John , Saunders Katie , Hensel Elizabeth , Kroese Biza Stenfert
Published: March 2005

The study aimed to identify factors that may affect the likelihood that people with intellectual disabilities will find employment through a supported employment agency. A retrospective analysis of the files of the last 200 individuals to use such an agency was carried out. Variables were identified that may influence outcome, such as demographic factors, job preferences and identified support needs. A specific rating of staff assessed client motivation was developed from written comments made by staff. Staff assessed motivation after two weeks on the scheme was found to be the only significant predictor of employment outcome. Motivation levels decreased for all groups of participants while at the agency, irrespective of work outcome. This study highlights that a greater emphasis on motivation within employment agencies may increase the chances of people with intellectual disability finding work.
Patterns of leisure participation among adolescents with a mild intellectual disability
Authors: Buttimer John , Tierney Edel
Published: March 2005

The aim of this study was to investigate the leisure and recreational activities of a cohort of 34 students attending a full-time special school as reported by the students and their parents. Leisure activities which were mostly solitary and passive in nature were identified as those being most commonly engaged in. Barriers to leisure were also identified, with ‘access to’ and ‘location of’ the leisure facilities being barriers perceived by both students and parents. Data on aspects of leisure use, e.g. enjoyment, participation, assistance required, socialization and choice, were also collected.
Sibshops
Authors: D’Arcy Fiona , Flynn Jacinta , McCarthy Yvonne , O’Connor Catherine , Tierney Edel
Published: March 2005

The study evaluates the effectiveness of a sibling support programme (Sibshops) involving three disability agencies in Cork, Ireland. Qualitative and quantitative data were obtained using semi-structured interviews and the Piers-Harris Children’s Self-Concept Scale with siblings, together with parent feedback. Results from the Piers-Harris showed that there was no significant increase in sibling self-esteem following attendance at the Sibshops. However, the interviews revealed that the majority of siblings enjoyed and benefited from the Sibshops. Parents reported satisfaction with the Sibshops and felt that their children had benefited. Reflections on the experience of working on an interagency basis are outlined. Recommendations are made regarding further research and development in the organization of Sibshops and in staffing and staff training.
Self-reported smoking and alcohol use among adolescents with intellectual disabilities
Authors: Emerson Eric , Turnbull Lorraine
Published: March 2005

Self-reported smoking and alcohol use were examined among 95 adolescents (aged 11-15) with intellectual disabilities and 4069 adolescents who did not have intellectual disabilities. Results indicated that adolescents with intellectual disabilities reported increased rates of smoking and decreased rates of using alcohol at least once a month. There were no marked differences between the two groups on smoking seven or more cigarettes a day, having ever smoked at all and having ever used alcohol. Elevated levels of smoking appeared to be an artefact of increased rates of poverty among adolescents with intellectual disabilities. Distinct patterns of risk were associated with smoking and alcohol use among adolescents with intellectual disabilities. Smoking was closely associated with the experience of poverty and adolescent mental health. Alcohol use was associated with less punitive child management practices and carer mental health. Results are discussed in the context of health promotion.
Suspects who have a learning disability
Authors: Gendle Kate , Woodhams Jessica
Published: March 2005

More than a million people in the UK have a learning disability. A small but significant proportion of these people will come into contact with the criminal justice system because they have offended or have been accused of an offence. This article reports on the perceptions of police officers toward this potentially vulnerable group and their knowledge of issues related to learning disabilities. Interview data were collected from eight police sergeants employed by Humberside Police and analysed using qualitative techniques. The article concludes that further training in the subject area is required. This is likely to be successful in the force under study due to their promotion of positive perceptions toward people with learning disabilities.
Tissue-factor–bearing microvesicles arise from lipid rafts and fuse with activated platelets to initiate coagulation
Authors: del Conde Ian , Shrimpton Corie N. , Thiagarajan Perumal , López José A.
Published: March 2005

Tissue factor (TF) circulates in plasma, largely on monocyte/macrophage-derived microvesicles that can bind activated platelets through a mechanism involving P-selectin glycoprotein ligand-1 (PSGL-1) on the microvesicles and P-selectin on the platelets. We found these microvesicles to be selectively enriched in both TF and PSGL-1, and deficient in CD45, suggesting that they arise from distinct membrane microdomains. We investigated the possibility that microvesicles arise from cholesterol-rich lipid rafts and found that both TF and PSGL-1, but not CD45, localize to lipid rafts in blood monocytes and in the monocytic cell line THP-1. Consistent with a raft origin of TF-bearing microvesicles, their shedding was significantly reduced with depletion of membrane cholesterol. We also evaluated the interaction between TF-bearing microvesicles and platelets. Microvesicles bound only activated platelets, and required PSGL-1 to do so. The microvesicles not only bound the activated platelets, they fused with them, transferring both proteins and lipid to the platelet membrane. Fusion was blocked by either annexin V or an antibody to PSGL-1 and had an important functional consequence: increasing the proteolytic activity of the TF-VIIa complex. These findings suggest a mechanism by which all of the membrane-bound reactions of the coagulation system can be localized to the surface of activated platelets.
Myelodysplasia and acute myeloid leukemia following therapy for indolent lymphoma with fludarabine, mitoxantrone, and dexamethasone (FND) plus rituximab and interferon alpha
Authors: McLaughlin Peter , Estey Elihu , Glassman Armand , Romaguera Jorge , Samaniego Felipe , Ayala Ana , Hayes Kimberly , Maddox Anne Marie , Preti H. Alejandro , Hagemeister Fredrick B.
Published: March 2005

Treatment-related myelodysplasia (t-MDS) occurs less frequently with the nucleoside analogs than with DNA-damaging agents such as alkylators or topoisomerase II inhibitors. In a chemoimmunotherapy trial conducted between 1997 and 2003 in patients with stage IV indolent lymphoma, 202 patients were treated and 8 have developed MDS between 1 and 5 years after therapy, including 4 who received only fludarabine, mitoxantrone, and dexamethasone (FND) for 6 to 8 courses, with or without rituximab, followed by interferon alpha (IFN-α). Complex cytogenetic abnormalities were present in all patients. Abnormalities of chromosome 7 were present in 6 of the 8 patients, 3 of whom received only FND ± rituximab and IFN-α. The abnormalities of chromosome 7 were monosomy 7 in 4 patients (1 of which had add 7p in the remaining chromosome); 1 del 7q; and 1 der 7. MDS with features classically associated with DNA-damaging agents can occur following therapy with FND, with or without rituximab, and IFN-α. (Blood. 2005;105:4573-4575)
Human TSLP promotes CD40 ligand-induced IL-12 production by myeloid dendritic cells but maintains their Th2 priming potential
Authors: Watanabe Norihiko , Hanabuchi Shino , Marloie-Provost Marie-Annick , Antonenko Svetlana , Liu Yong-Jun , Soumelis Vassili
Published: March 2005

Interleukin-4 (IL-4), a major T-helper type 2 (Th2) cytokine, primes dendritic cells (DCs) for IL-12 production, suggesting a negative feedback loop to prevent dysregulated Th2 inflammation, such as allergy. We previously showed that human thymic stromal lymphopoietin (TSLP), highly expressed by keratinocytes of atopic dermatitis, activates CD11c+ DCs to induce the differentiation of naive CD4+ and CD8+ T cells into proallergic effectors. Here we show that TSLP primes DCs to produce large amounts of IL-12 after CD40 ligand stimulation, similar to IL-4 priming of DCs. In contrast to IL-4 priming, DCs activated with TSLP and CD40 ligand induce the differentiation of naive CD4+ T cells into effectors producing both Th1 and Th2 cytokines, a unique profile that is reminiscent of the late phase of allergy. Thus, TSLP is a major regulatory cytokine for IL-12 production by DCs, and TSLP-activated DCs could promote the persistence of Th2 inflammation even in the presence of IL-12-inducing signals. (Blood. 2005;105:4749-4751)
Thalidomide-induced antiangiogenic action is mediated by ceramide through depletion of VEGF receptors, and is antagonized by sphingosine-1-phosphate
Authors: Yabu Takeshi , Tomimoto Hidekazu , Taguchi Yoshimitsu , Yamaoka Shohei , Igarashi Yasuyuki , Okazaki Toshiro
Published: March 2005

Thalidomide, which is clinically recognized as an efficient therapeutic agent for multiple myeloma, has been thought to exert antiangiogenic action through an unknown mechanism. We here show a novel mechanism of thalidomide-induced antiangiogenesis in zebrafish embryos. Thalidomide induces the defect of major blood vessels, which is demonstrated by their morphologic loss and confirmed by the depletion of vascular endothelial growth factor (VEGF) receptors such as neuropilin-1 and Flk-1. Transient increase of ceramide content through activation of neutral sphingomyelinase (nSMase) precedes thalidomide-induced vascular defect in the embryos. Synthetic cell permeable ceramide, N-acetylsphingosine (C2-ceramide) inhibits embryonic angiogenesis as well as thalidomide. The blockade of ceramide generation by antisense morpholino oligonucleotides for nSMase prevents thalidomide-induced ceramide generation and vascular defect. In contrast to ceramide, sphingosine-1-phosphate (S1P) inhibits nSMase-dependent ceramide generation and restores thalidomide-induced embryonic vascular defect with an increase of expression of VEGF receptors. In human umbilical vein endothelial cells (HUVECs), thalidomide-induced inhibition of cell growth, generation of ceramide through nSMase, and depletion of VEGF receptors are restored to the control levels by pretreatment with S1P. These results suggest that thalidomide-induced antiangiogenic action is regulated by the balance between ceramide and S1P signal.
Fibromodulin, an extracellular matrix protein: characterization of its unique gene and protein expression in B-cell chronic lymphocytic leukemia and mantle cell lymphoma
Authors: Mikaelsson Eva , Danesh-Manesh Amir Hossein , Lüppert Alfred , Jeddi-Tehrani Mahmood , Rezvany Mohammad-Reza , Sharifian Ramazan Ali , Safaie Reza , Roohi Azam , Österborg Anders , Shokri Fazel , Mellstedt Håkan , Rabbani Hodjattallah
Published: March 2005

Fibromodulin is an extracellular matrix protein normally produced by collagen-rich tissues; the fibromodulin gene has been found to be the most overexpressed gene in B-cell chronic lymphocytic leukemia. In this study, fibromodulin was expressed at the gene level (reverse transcription-polymerase chain reaction [RT-PCR]) in all patients with B-CLL (n = 75) and in most (5 of 7) patients with mantle cell lymphoma (MCL). No mutations in the fibromodulin gene were detected. Fibromodulin was also detected at the protein level in the cytoplasm of the B-CLL cells and in the supernatant after in vitro cultivation, but not at the cell surface. Fibromodulin was not found in patients with T-cell chronic lymphocytic leukemia (T-CLL), B-cell prolymphocytic leukemia (B-PLL), T-cell prolymphocytic leukemia (T-PLL), hairy cell leukemia, follicular lymphoma, lymphoplasmacytic lymphoma, multiple myeloma, acute lymphoblastic leukemia (ALL), acute myelogenous leukemia (AML), or chronic myelogenous leukemia (CML) or in 36 hematologic cell lines. Normal blood mononuclear cells (T and B lymphocytes, monocytes), tonsil B cells, and granulocytes did not express fibromodulin. Activation (phorbol 12-myristate 13-acetate [PMA]/ionomycin) of normal T and B lymphocytes induced weak fibromodulin gene expression, but not to the extent seen in freshly isolated B-CLL cells. The reason for the exclusive ectopic expression of fibromodulin in B-CLL and MCL is unknown. However, its unique protein expression makes it likely that fibromodulin is involved in the pathobiology of B-CLL and MCL. (Blood. 2005;105:4828-4835)
Copper-dependent activation of hypoxia-inducible factor (HIF)-1: implications for ceruloplasmin regulation
Authors: Martin Falk , Linden Tobias , Katschinski Dörthe M. , Oehme Felix , Flamme Ingo , Mukhopadhyay Chinmay K. , Eckhardt Katrin , Tröger Juliane , Barth Sandra , Camenisch Gieri , Wenger Roland H.
Published: March 2005

Cellular oxygen partial pressure is sensed by a family of prolyl-4-hydroxylase domain (PHD) enzymes that modify hypoxia-inducible factor (HIF)α subunits. Upon hydroxylation under normoxic conditions, HIFα is bound by the von Hippel-Lindau tumor suppressor protein and targeted for proteasomal destruction. Since PHD activity is dependent on oxygen and ferrous iron, HIF-1 mediates not only oxygen- but also iron-regulated transcriptional gene expression. Here we show that copper (CuCl2) stabilizes nuclear HIF-1α under normoxic conditions, resulting in hypoxia-response element (HRE)-dependent reporter gene expression. In in vitro hydroxylation assays CuCl2 inhibited prolyl-4-hydroxylation independently of the iron concentration. Ceruloplasmin, the main copper transport protein in the plasma and a known HIF-1 target in vitro, was also induced in vivo in the liver of hypoxic mice. Both hypoxia and CuCl2 increased ceruloplasmin (as well as vascular endothelial growth factor [VEGF] and glucose transporter 1 [Glut-1]) mRNA levels in hepatoma cells, which was due to transcriptional induction of the ceruloplasmin gene (CP) promoter. In conclusion, our data suggest that PHD/HIF/HRE-dependent gene regulation can serve as a sensory system not only for oxygen and iron but also for copper metabolism, regulating the oxygen-, iron- and copper-binding transport proteins hemoglobin, transferrin, and ceruloplasmin, respectively. (Blood. 2005;105:4613-4619)
Telomere loss, senescence, and genetic instability in CD4+ T lymphocytes overexpressing hTERT
Authors: Röth Alexander , Baerlocher Gabriela M. , Schertzer Mike , Chavez Elizabeth , Dührsen Ulrich , Lansdorp Peter M.
Published: March 2005

Little is known about the long-term consequences of overexpression of the human telomerase reverse transcriptase (hTERT) gene in T lymphocytes. To address this issue, we transduced polyclonal as well as clonally derived populations of naive and memory CD4+ T cells from 2 healthy donors (aged 24 and 34 years) with retroviral vectors encoding green fluorescence protein (GFP) and hTERT (GFP-hTERT) or GFP alone. After transduction, cells were sorted on the basis of GFP expression and cultured in vitro until senescence. T cells transduced with hTERT exhibited high stable telomerase activity throughout the culture period. Relative to GFP controls, minor changes in overall gene expression were observed yet the proliferative lifespan of the hTERT-transduced populations was significantly increased and the rate of telomere loss was lower. Nevertheless, hTERT-transduced cells showed progressive telomere loss and had shorter telomeres at senescence than controls (2.3 ± 0.3 kilobase [kb] versus 3.4 ± 0.1 kb). Furthermore, a population of cells with 4N DNA consisting of binucleated cells with connected nuclei emerged in the hTERT-transduced cells prior to senescence. We conclude that overexpression of hTERT in CD4+ T cells provides a proliferative advantage independent of the average telomere length but does not prevent eventual genetic instability and replicative senescence.
Expression of SphK1 impairs degranulation and motility of RBL-2H3 mast cells by desensitizing S1P receptors
Authors: Jolly Puneet S. , Bektas Meryem , Watterson Kenneth R. , Sankala Heidi , Payne Shawn G. , Milstien Sheldon , Spiegel Sarah
Published: March 2005

Mast cells play a central role in inflammatory and immediate-type allergic reactions by secreting a variety of biologically active substances, including sphingosine-1 phosphate (S1P). Sphingosine kinase 1 (SphK1) and formation of S1P, which leads to transactivation of S1P receptors and their downstream signaling pathways, regulates mast-cell functions initiated by cross-linking of the high-affinity immunoglobulin E (IgE) receptor FcϵRI. Surprisingly, overexpression of SphK1 in rat basophilic leukemia (RBL)-2H3 mast cells impaired degranulation as well as migration toward antigen. These effects were reversed by serum withdrawal, yet the increased formation and secretion of S1P were the same as in the presence of serum. Nonetheless, serum increased localization of SphK1 at the plasma membrane. This restricted formation of S1P induced internalization and desensitization of S1P receptors on the surface of mast cells as determined by confocal immunofluorescence microscopy, aberrant S1P receptor signaling, and lack of S1P receptor coupling to G proteins. Serum starvation, which significantly reduced membrane-associated SphK1 activity, restored S1P receptor functions. Our results have important implications for mast-cell migration and degranulation as well as for the biologic functions of the S1P receptors on cells that are circulating in the bloodstream. (Blood. 2005;105:4736-4742)
Phenotypic characterization of the human myeloma cell growth fraction
Authors: Robillard Nelly , Pellat-Deceunynck Catherine , Bataille Régis
Published: March 2005

In this study we quantified the proliferation rate of normal and malignant plasma cells (PCs) by ex vivo incorporation of 5-bromo-2′-deoxyuridine (BrdU; labeling index, LI) using flow cytometry. We show that all bone marrow PCs, either normal or malignant, include a subset of proliferating PCs present within the CD45bright fraction. Indeed, medullary normal and malignant PCs were always heterogeneous for CD45 expression, and proliferation was always restricted primarily to the CD45bright compartment. Moreover, an inverse correlation was found between LI or CD45 and B-cell lymphoma 2 (Bcl-2) in both malignant and normal PCs, the most proliferating CD45bright PCs have the lowest Bcl-2 expression. We investigated expression of molecules of interest in multiple myeloma (MM)—that is, CD138, CD19, CD20, CD27, CD28, CD56, and CD11a—to further characterize the CD45bright fraction. Among all of these molecules, only CD11a was exclusively expressed by CD45bright proliferating myeloma cells. In conclusion, proliferating myeloma cells are characterized by the specific CD45bright CD11apos Bcl-2low phenotype. (Blood. 2005;105:4845-4848)
Low Mpl receptor expression in a pedigree with familial platelet disorder with predisposition to acute myelogenous leukemia and a novel AML1 mutation
Authors: Heller Paula G. , Glembotsky Ana C. , Gandhi Manish J. , Cummings Carrie L. , Pirola Carlos J. , Marta Rosana F. , Kornblihtt Laura I. , Drachman Jonathan G. , Molinas Felisa C.
Published: March 2005

Germ-line heterozygous mutations in the hematopoietic transcription factor AML1 (RUNX1) have been identified in patients with familial platelet disorder with predisposition to acute myelogenous leukemia (FPD/AML), which is characterized by thrombocytopenia, abnormal platelet function, and propensity to myeloid malignancies. We identified a novel mutation in the AML1 gene in an FPD/AML pedigree characterized by a single nucleotide deletion that generates a frameshift and premature chain termination (Pro218fs-Ter225). Both wild-type and mutant transcripts were expressed in affected individuals by allele-specific reverse transcriptase-polymerase chain reaction (RT-PCR). Thrombopoietin (TPO) binds to the Mpl receptor and is the major regulator of megakaryopoiesis. To explore the mechanisms underlying thrombocytopenia, we studied the TPO/Mpl pathway in this newly identified pedigree. TPO levels were mildly to moderately elevated. On flow cytometry and immunoblotting, Mpl receptor expression was decreased and TPO-induced signaling was impaired. While no mutations were identified in the MPL gene by sequence analysis, low MPL mRNA levels were found, suggesting decreased gene expression. Of particular interest, several AML1-binding motifs are present in the MPL promoter, suggesting MPL is an AML1 target. In conclusion, we identified a C-terminal AML1 mutation that leads to a decrease in Mpl receptor expression, providing a potential explanation for thrombocytopenia in this FPD/AML pedigree. (Blood. 2005;105:4664-4670)
Acute effects of cigarette smoking on inflammation in healthy intermittent smokers
Authors: van der Vaart Hester , Postma Dirkje S , Timens Wim , Hylkema Machteld N , Willemse Brigitte WM , Boezen H Marike , Vonk Judith M , de Reus Dorothea M , Kauffman Henk F , ten Hacken Nick HT
Published: March 2005

Background

Chronic smoking is the main risk factor for chronic obstructive pulmonary disease. Knowledge on the response to the initial smoke exposures might enhance the understanding of changes due to chronic smoking, since repetitive acute smoke effects may cumulate and lead to irreversible lung damage.

Methods

We investigated acute effects of smoking on inflammation in 16 healthy intermittent smokers in an open randomised cross-over study. We compared effects of smoking of two cigarettes on inflammatory markers in exhaled air, induced sputum, blood and urine at 0, 1, 3, 6, 12, 24, 48, 96 and 192 hours and outcomes without smoking. All sputum and blood parameters were log transformed and analysed using a linear mixed effect model.

Results

Significant findings were: Smoking increased exhaled carbon monoxide between 0 and 1 hour, and induced a greater decrease in blood eosinophils and sputum lymphocytes between 0 and 3 hours compared to non-smoking. Compared to non-smoking, smoking induced a greater interleukin-8 release from stimulated blood cells between 0 and 3 hours, and a greater increase in sputum lymphocytes and neutrophils between 3 and 12 hours.

Conclusion

We conclude that besides an increase in inflammation, as known from chronic smoking, there is also a suppressive effect of smoking two cigarettes on particular inflammatory parameters.
htSNPer1.0: software for haplotype block partition and htSNPs selection
Authors: Ding Keyue , Zhang Jing , Zhou Kaixin , Shen Yan , Zhang Xuegong
Published: March 2005

Background

There is recently great interest in haplotype block structure and haplotype tagging SNPs (htSNPs) in the human genome for its implication on htSNPs-based association mapping strategy for complex disease. Different definitions have been used to characterize the haplotype block structure in the human genome, and several different performance criteria and algorithms have been suggested on htSNPs selection.

Results

A heuristic algorithm, generalized branch-and-bound algorithm, is applied to the searching of minimal set of haplotype tagging SNPs (htSNPs) according to different htSNPs performance criteria. We develop a software htSNPer1.0 to implement the algorithm, and integrate three htSNPs performance criteria and four haplotype block definitions for haplotype block partitioning. It is a software with powerful Graphical User Interface (GUI), which can be used to characterize the haplotype block structure and select htSNPs in the candidate gene or interested genomic regions. It can find the global optimization with only a fraction of the computing time consumed by exhaustive searching algorithm.

Conclusion

htSNPer1.0 allows molecular geneticists to perform haplotype block analysis and htSNPs selection using different definitions and performance criteria. The software is a powerful tool for those focusing on association mapping based on strategy of haplotype block and htSNPs.
The Use of Edge-Betweenness Clustering to Investigate Biological Function in Protein Interaction Networks
Authors: Dunn Ruth , Dudbridge Frank , Sanderson Christopher M
Published: March 2005

Background

This paper describes an automated method for finding clusters of interconnected proteins in protein interaction networks and retrieving protein annotations associated with these clusters.

Results

Protein interaction graphs were separated into subgraphs of interconnected proteins, using the JUNG implementation of Girvan and Newman's Edge-Betweenness algorithm. Functions were sought for these subgraphs by detecting significant correlations with the distribution of Gene Ontology terms which had been used to annotate the proteins within each cluster. The method was implemented using freely available software (JUNG and the R statistical package). Protein clusters with significant correlations to functional annotations could be identified and included groups of proteins know to cooperate in cell metabolism. The method appears to be resilient against the presence of false positive interactions.

Conclusion

This method provides a useful tool for rapid screening of small to medium size protein interaction datasets.
Genetic linkage analysis supports the presence of two susceptibility loci for alcoholism and heavy drinking on chromosome 1p22.1-11.2 and 1q21.3-24.2
Authors: Guerrini Irene , Cook Christopher CH , Kest Wendy , Devitgh Audrey , McQuillin Andrew , Curtis David , Gurling Hugh MD
Published: March 2005

Background

In order to confirm a previous finding of linkage to alcoholism on chromosome 1 we have carried out a genetic linkage study.

Methods

DNA from eighteen families, densely affected by alcoholism, was used to genotype a set of polymorphic microsatellite markers at loci approximately 10 centimorgans apart spanning the short arm and part of the long arm of chromosome 1. Linkage analyses were performed using the classical lod score and a model-free method. Three different definitions of affection status were defined, these were 1. Heavy Drinking (HD) where affected subjects drank more than the Royal College of Psychiatrists recommended weekly amount. 2. The Research Diagnostic Criteria for alcoholism (RDCA) 3. Alcohol Dependence Syndrome (ADS) as defined by Edwards and Gross (1976) and now incorporated into ICD10 and DSMIV.

Results

Linkage analyses with the markers D1S1588, D1S2134, D1S1675 covering the cytogenetic region 1p22.1-11.2 all gave positive two point and multipoint lods with a maximum lod of 1.8 at D1S1588 (1p22.1) for the RDCA definition of alcoholism. Another lod of 1.8 was found with D1S1653 in the region 1q21.3-24.2 using the HD affection model.

Conclusion

These results both support the presence of linkage in the 1p22.1-11.2 region which was previously implicated by the USA Collaborative Study of the Genetics of Alcoholism (COGA) study and also suggest the presence of another susceptibility locus at 1q21.3-24.2.
A robust method for the amplification of RNA in the sense orientation
Authors: Marko Nicholas F , Frank Bryan , Quackenbush John , Lee Norman H
Published: March 2005

Background

Small quantities of RNA (1–4 μg total RNA) available from biological samples frequently require a single round of amplification prior to analysis, but current amplification strategies have limitations that may restrict their usefulness in downstream genomic applications. The Eberwine amplification method has been extensively validated but is limited by its ability to produce only antisense RNA. Alternatives lack extensive validation and are often confounded by problems with bias or yield attributable to their greater biological and technical complexity.

Results

To overcome these limitations, we have developed a straightforward and robust protocol for amplification of RNA in the sense orientation. This protocol is based upon Eberwine's method but incorporates elements of more recent amplification techniques while avoiding their complexities. Our technique yields greater than 100-fold amplification, generates long transcript, and produces mRNA that is well suited for use with microarray applications. Microarrays performed with RNA amplified using this protocol demonstrate minimal amplification bias and high reproducibility.

Conclusion

The protocol we describe here is readily adaptable for the production of sense or antisense, labeled or unlabeled RNA from intact or partially-degraded prokaryotic or eukaryotic total RNA. The method outperforms several commercial RNA amplification kits and can be used in conjunction with a variety of microarray platforms, such as cDNA arrays, oligonucleotide arrays, and Affymetrix GeneChip™ arrays.
General practitioner attitudes to the care of people with epilepsy: an examination of clustering within practices and prediction of patient-rated quality of care
Authors: Thapar Ajay K , Roland Martin O
Published: March 2005

Background

There is wide variation in the quality of care provided by primary care practices to individuals with chronic illnesses. Individual doctor attitudes and interest have been demonstrated to influence patient outcomes in some instances. Given the trend towards larger practices and part-time working, continuity of care is likely to fall and thus practice-based rather than individual general practitioner attributes and attitudes are likely to become increasingly important. The aim in this paper was to examine the extent to which individual general practitioner (G.P.) attitudes to the care of people with epilepsy cluster within practices and predict patient-rated quality of care.

Methods

The sample consisted of 1255 people with active epilepsy (a recent seizure or on anti-convulsant medication for epilepsy) and 199 GPs from 82 general practices. Measures of GP attitudes (a 17-item GP attitudes questionnaire) and patient-rated quality of epilepsy care were obtained. 1210 individuals completed initial questionnaires and 975 patients filled in final questionnaires one year later. Responses were achieved from 64 practices (83% of total) and 115 GPs (60% of total).

Results

2 main factors were found to underlie GP attitudes to the care of people with epilepsy and these demonstrated clustering within practices "epilepsy viewed as a primary care responsibility" (Eigenvalue 3.98, intra-class correlation coefficient (ICC) 0.40), and "medication skills"(Eigenvalue 2.74, ICC 0.35). GP-rated scores on "epilepsy care being a primary care responsibility" were a significant predictor of patient-rated quality of GP care (p = 0.031). Other contributory factors were seizure frequency (p = 0.044), and patient-rated "shared decision making" (p = 0.022).

Conclusion

Specific general practitioner attitudes to the care of people with epilepsy cluster within practices and are significantly associated with patient-rated quality of epilepsy care. It is important to take these findings into consideration when planning primary care interventions to ensure people with epilepsy receive the benefits of available medical and surgical expertise.
Human desmoid fibroblasts: matrix metalloproteinases, their inhibitors and modulation by Toremifene
Authors: Balducci Chiara , Lilli Cinzia , Stabellini Giordano , Marinucci Lorella , Giustozzi Giammario , Becchetti Alessio , Cagini Lucio , Locci Paola
Published: March 2005

Background

Desmoid tumour is a benign, non metastasising neoplasm characterised by an elevated deposition of organic macromolecules in the extracellular matrix (ECM). The matrix metalloproteinases (MMPs) are a family of zinc-dependent proteinases involved in the degradation of ECM macromolecules. The MMPs and their natural inhibitors (TIMPs) have been implicated in tumour growth, invasion and metastasis. In this study we provide evidence that the in vitro cultured cell line from desmoid tumour accumulates more collagen fibres in the ECM than healthy fibroblasts.

Methods

We investigated collagen accumulation by 3H-thymidine incorporation, MMP expression by substrate gel zymography and TIMP expression by Western blot analysis.

Results

Desmoid fibroblasts showed a reduction in MMP activity and an increase of type I and III collagen and TIMPs compared to normal fibroblasts.

Conclusion

The increase in collagen in desmoid fibroblasts was due to inhibited collagen degradation (reduction of MMP activity) rather than to increased collagen synthesis. Adding toremifene, an anti-estrogen triphenylethylene derivate, to desmoid fibroblasts reduced collagen accumulation by decreasing mRNA expression and increasing collagen degradation.
Low frequency of defective mismatch repair in a population-based series of upper urothelial carcinoma
Authors: Ericson Kajsa M , Isinger Anna P , Isfoss Björn L , Nilbert Mef C
Published: March 2005

Background

Upper urothelial cancer (UUC), i.e. transitional cell carcinomas of the renal pelvis and the ureter, occur at an increased frequency in patients with hereditary nonpolyposis colorectal cancer (HNPCC). Defective mismatch repair (MMR) specifically characterizes HNPCC-associated tumors, but also occurs in subsets of some sporadic tumors, e.g. in gastrointestinal cancer and endometrial cancer.

Methods

We assessed the contribution of defective MMR to the development of UUC in a population-based series from the southern Swedish Cancer Registry, through microsatellite instability (MSI) analysis and immunohistochemical evaluation of expression of the MMR proteins MLH1, PMS2, MSH2, and MSH6.

Results

A MSI-high phenotype was identified in 9/216 (4%) successfully analyzed patients and a MSI-low phenotype in 5/216 (2%). Loss of MMR protein immunostaining was found in 11/216 (5%) tumors, and affected most commonly MSH2 and MSH6.

Conclusion

This population-based series indicates that somatic MMR inactivation is a minor pathway in the development of UUC, but tumors that display defective MMR are, based on the immunohistochemical expression pattern, likely to be associated with HNPCC.
Age and manifestation related symptoms in familial adenomatous polyposis
Authors: Croner Roland S , Brueckl Wolfgang M , Reingruber Bertram , Hohenberger Werner , Guenther Klaus
Published: March 2005

Background

To identify early symptoms of familial adenomatous polyposis with a view to improve early diagnosis and treatment. Diagnosis on the basis of genetic testing is usually limited to where there is a known family history, so FAP is more usually diagnosed on clinical grounds. Except for those identified via FAP registers, the majority of patients are symptomatic at the time of diagnosis.

Methods

We undertook a retrospective study of 143 FAP patients treated at the Department of Surgery, University of Erlangen between 1971 and 2000. We identified patterns of symptoms, endoscopic findings and extracolonic manifestations in three age groups.

Results

FAP was diagnosed clinically on the basis of symptoms in 84% (120/143) of these patients. Most presented with intestinal symptoms such as colonic bleeding (68%) and diarrhea (42%). All but one of the patients between 20 and 40 years old had rectal polyps (98.7%, 75/76), whereas in those over 40 years old the prevalence was 76% (35/46). Non-specific symptoms such as abdominal pain, fatigue and bloating were less frequent and were mainly reported by patients older than 40.

Conclusion

The commonest presenting features of FAP are alteration of bowel habit and rectal bleeding, but both are found in many other conditions. Patients with these findings need immediate endoscopy to allow prompt diagnosis and prophylactic surgery.
The prevalence of dental erosion in Nigerian patients with gastro-oesophageal reflux disease
Authors: Oginni Adeleke O , Agbakwuru Elugwaraonu A , Ndububa Dennis A
Published: March 2005

Background

In various people of the Western world, gastro-oesophageal reflux (GOR) has been reported to be a common problem. Various studies have also assessed the relationship between GOR and dental erosion. The authors are not aware of such studies in Nigerians. It is therefore the aims of the present study to estimate the prevalence of GOR; to estimate the prevalence of dental erosion in patients with GORD; to document the oral findings in patients diagnosed with GORD and to compare these findings with previous studies elsewhere.

Methods

A total of 225 subjects comprising of 100 volunteers and 125 patients diagnosed with GORD were involved in this study. History of gastric juice regurgitation and heartburn were recorded. Oral examination to quantify loss of tooth structure was done using the tooth wear index (TWI) designed by Smith and Knight (1984).

Results

Twenty patients with GORD presented with dental erosion in the maxillary anterior teeth with TWI scores ranging from 1–3. The prevalence of erosion was found to be statistically significant between GORD patients (16%) and control (5%) (p < 0.05), but not significant between endoscopic diagnostic groups (p > 0.05).

Conclusion

The present study supports the consideration of dental erosion as the extra-oesophageal manifestation of GORD. However the association between GORD and burning mouth sensation needs more investigation.
Salivary changes and dental caries as potential oral markers of autoimmune salivary gland dysfunction in primary Sjögren's syndrome
Authors: Pedersen Anne Marie Lynge , Bardow Allan , Nauntofte Birgitte
Published: March 2005

Background

the classification criteria for primary Sjögren's syndrome (pSS) include a number of oral components. In this study we evaluated if salivary flow and composition as well as dental caries are oral markers of disease severity in pSS.

Methods

in 20 patients fulfilling the American-European Consensus criteria for pSS and 20 age-matched healthy controls whole and parotid saliva flow rates and composition, measures of oral dryness, scores of decayed, missing and filled tooth surfaces (DMFS), periodontal indices, oral hygiene, and dietary habits were examined.

Results

in pSS, salivary flow rates, pH, and buffer capacities were lower, and DMFS, salivary sodium and chloride concentrations higher than in the healthy controls. DMFS also correlated inversely to salivary flow rates and positively to oral dryness. Apart from slightly increased gingival index, and more frequent dental visits in pSS, the periodontal condition, oral hygiene or sugar intake did not differ between these two groups. In pSS, findings were correlated to labial salivary gland focus score (FS) and presence of serum-autoantibodies to SSA/SSB (AB). The patients having both presence of AB and the highest FS (>2) also had the highest salivary sodium and chloride concentrations, the lowest salivary phosphate concentrations, lowest salivary flow rates, and highest DMFS compared to those with normal salivary concentrations of sodium and chloride at a given flow rate.

Conclusion

the salivary changes observed in some pSS patients reflect impaired ductal salt reabsorption, but unaffected acinar transport mechanisms, despite low salivary secretion. Our results suggest that changes in salivary flow and composition as well as dental caries may serve as potential markers of the extent of autoimmune-mediated salivary gland dysfunction in pSS. The study also indicates that the ductal epithelium is functionally affected in some pSS patients, which calls for future pathophysiological studies on the mechanisms underlying this impaired salt reabsorption.
Ultrasound imaging versus morphopathology in cardiovascular diseases. Coronary collateral circulation and atherosclerotic plaque
Authors: Baroldi Giorgio , Bigi Riccardo , Cortigiani Lauro
Published: March 2005

This review article is aimed at comparing the results of histopathological and clinical imaging studies to assess coronary collateral circulation in humans. The role of collaterals, as emerging from morphological studies in both normal and atherosclerotic coronary vessels, is described; in addition, present role and future perpectives of echocardiographic techniques in assessing collateral circulation are briefly summarized.
The Future of Smallpox Vaccination: is MVA the key?
Authors: Slifka Mark K
Published: March 2005

Eradication of the smallpox virus through extensive global vaccination efforts has resulted in one of the most important breakthroughs in medical history, saving countless lives from the severe morbidity and mortality that is associated with this disease. Although smallpox is now extinct in nature, laboratory stocks of this virus still remain and the subject of smallpox vaccination has gained renewed attention due to the potential risk that smallpox may be used as a biological weapon by terrorists or rogue states. Despite having the longest history of any modern vaccine, there is still much to be learned about smallpox vaccination and the correlates of protection remain to be formally defined. This Commentary will discuss the strengths and weaknesses of traditional smallpox vaccination in comparison with immunization using modified vaccinia virus Ankura (MVA), a non-replicating virus with a strong safety record but weakened immunogenicity.
Locally advanced duodenal gangliocytic paraganglioma treated with adjuvant radiation therapy: case report and review of the literature
Authors: Wong Adrian , Miller Alexander R , Metter John , Thomas Charles R
Published: March 2005

Background

Gangliocytic paraganglioma are rare neoplasms that predominantly arise in periampulary region. Though considered benign the disease can spread to regional lymphatics.

Case presentation

A 49 year old woman presented with melena and was found to have a periampullary mass. Endoscopic evaluation and biopsy demonstrated a periampullary paraganglioma. The tumor was resected with pylorus-preserving pancreaticoduodenectomy and was found to represent a gangliocytic paraganglioma associated with nodal metastases. In a controversial decision, the patient was treated with adjuvant external beam radiation therapy. She is alive and well one year following resection. The authors have reviewed the current literature pertaining to this entity and have discussed the biologic behavior of the tumor as well as the rationale for treatment strategies employed.

Conclusion

Paraganglioma is a rare tumor that typically resides in the gastrointestinal tract and demonstrates low malignant potential. Due to rarity of the disease there is no consensus on the adjuvant treatment even though nearly 5% of the lesions demonstrate the malignant potential.
Initial development and testing of a novel foam-based pressure sensor for wearable sensing
Authors: Dunne Lucy E , Brady Sarah , Smyth Barry , Diamond Dermot
Published: March 2005

Background

This paper provides an overview of initial research conducted in the development of pressure-sensitive foam and its application in wearable sensing. The foam sensor is composed of polypyrrole-coated polyurethane foam, which exhibits a piezo-resistive reaction when exposed to electrical current. The use of this polymer-coated foam is attractive for wearable sensing due to the sensor's retention of desirable mechanical properties similar to those exhibited by textile structures.

Methods

The development of the foam sensor is described, as well as the development of a prototype sensing garment with sensors in several areas on the torso to measure breathing, shoulder movement, neck movement, and scapula pressure. Sensor properties were characterized, and data from pilot tests was examined visually.

Results

The foam exhibits a positive linear conductance response to increased pressure. Torso tests show that it responds in a predictable and measurable manner to breathing, shoulder movement, neck movement, and scapula pressure.

Conclusion

The polypyrrole foam shows considerable promise as a sensor for medical, wearable, and ubiquitous computing applications. Further investigation of the foam's consistency of response, durability over time, and specificity of response is necessary.