bluuebunny/crossref_metadata_2025 huggingface dataset:
Pervasive Refusal Syndrome among Asylum-seeking Children
Authors: von Folsach Liv Lyngå , Montgomery Edith
Published: July 2006

A number of asylum-seeking children in Sweden have developed a pervasive loss of function associated with profound social withdrawal. The syndrome is called Depressive Devitalization. The aim of this study was to identify possible aetiological factors, outline the similarities between Depressive Devitalization and Pervasive Refusal Syndrome and to explore possible differential diagnoses. The research was based on a literature study. Databases searched included PsychINFO, Medline, Pub med, COCHRANE and PILOTS. Possible aetiological factors identified included: Children having a perfectionist, ambitious and conscientious premorbid personality, psychiatric problems of children and parents, and traumatic events. Symptoms between the two syndromes differed only in pattern of refusal and neurological symptoms. None of the differential diagnoses explored could account for all features. The individual impact of aetiological factors requires further investigation. Children might previously have been diagnosed with a number of differential diagnoses, though none of these accounts for all symptoms seen in the syndromes. Depressive Devitalization and Pervasive Refusal Syndrome are suggested to be subgroups of the same refusal syndrome.
Test of Time
Authors: Wright Shelagh
Published: July 2006

This article reviews the paper by Liebman, Minuchin, and Baker (1974) describing the use of a family meal as part of an integrated treatment approach for anorexia nervosa. The ideas laid out in the paper are described and discussed in terms of the understanding of anorexia nervosa at the time as well as placed in a current clinical and theoretical context. A comment is made on whether or not, in this author's opinion, the paper stands ‘the test of time’.
The Measurement and Prediction of Conditions within Indoor Microenvironments
Authors: Baker Paul H. , Galbraith Graham H. , McLean R. Craig , Hunter Colin , Sanders Chris H.
Published: July 2006

Biocontaminants, such as dust mites and microfungi, can live in building habitats with a spatial scale of only a few millimetres. With the recent development of very small size microchip-based sensors, it is now practicable to measure the humidity at different locations within these microenvironments. In the laboratory study described here, sensors were used to measure the conditions in a number of typical flooring systems using a variety of coverings. The measurements were compared with the predictions of a well-established and validated dynamic heat and moisture transfer simulation model. In order to provide an accurate input to the model, permeability and sorption tests were carried out on the flooring materials used. Finally, using monitored domestic environmental data, simulation results were coupled to a simplified growth model to predict dust mite activity in the flooring systems under realistic boundary conditions.
Use of CFD Modelling to Optimise the Design of Upper-room UVGI Disinfection Systems for Ventilated Rooms
Authors: Noakes C. J. , Sleigh P. A. , Fletcher L. A. , Beggs C. B.
Published: July 2006

The installation of upper-room ultraviolet germicidal irradiation (UVGI) devices in ventilated rooms has the potential to reduce transmission of infections by an airborne route. However, the performance of such devices is dependant on several factors including the location of the lamp and the ventilation airflow in the room. This study uses a CFD model to evaluate the performance of UVGI devices by considering the cumulative UV-C dose received by the bulk room air in a ventilated room. By evaluating the UV dose rather than the resulting micro-organism inactivation the methodology can be used to optimise UVGI systems at the design stage, particularly when the source location of bioaerosol contaminants is not known. The study investigates the relationships between the lamp location, lamp power, ventilation system and room heating in a small, ventilated room. The results show that with ventilation air supplied at low level and extracted at high level the UVGI system performs better than with the air supplied at high level and extracted close to the floor. In addition the results show the presence of a heater in the room is unlikely to have a detrimental effect on performance and may promote mixing to increase the extent of disinfection.
Environmental Discomfort and Geomagnetic Field Influence on Psychological Mood in Athens, Greece
Authors: Nastos P. T. , Paliatsos A. G. , Tritakis V. P. , Bergiannaki A.
Published: July 2006

A multivariate analysis of 4797 cases of patients who were cured of their psychological symptoms and their notes filed by the psychiatric clinic of the Eginition Hospital in Athens, during the year 1994, has been done. The results of this analysis imply significant contribution of environmental variations, expressed by a discomfort index, in the aggravation of psychological symptoms like depression, sleep disturbances, anxiety, aggressiveness, etc. Moreover, geomagnetic field variations expressed by the international geomagnetic index (DST) manifest significant indications that they contribute to the aggravation of sleep disturbances. A clear seasonal variation, with a maximum around August and a minimum at the end of the year, appears in the environmental index, while a double oscillation with a period of about six months is obvious in the geomagnetic index. The same more or less seasonal variation was mirrored in most of the psychological symptoms we analysed in the present study.
Mining the internet plateau: an exploration of the adoption intention of non-users in Singapore
Authors: Chia Stella C. , Li Hairong , Detenber Benjamin , Lee Waipeng
Published: July 2006

This study1 examines the factors that affect the intention to adopt the internet among non-users against the backdrop of an emerging internet plateau. Using data from a telephone survey with a representative national sample of non-users in Singapore, this study attempts to understand better what may facilitate or impede non-users to adopt the internet in light of the theory of planned behavior. Findings indicate that, in addition to demographic factors, attitudes toward the internet and perceived control of several internal and external factors are predictive of individuals’ intentions to get online in the future. Implications of the findings and future research directions are discussed.
Is the press release a genre? A study of form and content
Authors: Lassen Inger
Published: July 2006

Although using different labels, genre theorists from different traditions have generally given privilege to the communicative purpose, in this article referred to as rhetorical objective, as genre determinant (see e.g. Swales, 1990; Bhatia, 1993; see also Hasan, 1989; Halliday and Martin, 1993; Eggins, 1994). Genre analysts who have studied press releases in particular (e.g. Frandsen et al., 1997; Jacobs, 1999) tend to share this view, but nevertheless categorize communicative events conveyed through the press release as belonging to one genre despite variation in rhetorical objectives. This article argues that although the press release may be seen as a genre on the basis of textual form, it does not qualify for the genre label if analysed in terms of content and rhetorical objective. To substantiate my claim, I shall discuss a small corpus of press releases, all focusing on a specific biotechnological issue. In my analyses I shall discuss staging in terms of content as well as logico-semantic relations between stages, patterns of stage combinations and their linguistic realizations with the aim of identifying variation in rhetorical objective.
Telling about problems and giving advice in an Internet discussion forum: some discourse features
Authors: Morrow Phillip R.
Published: July 2006

This study describes discourse features of messages posted to an Internet discussion forum about depression based on the analysis of a small corpus of message texts. The message texts were classified into three types: problem messages, advice messages and thanks messages, and salient discourse features of each message type were described and analyzed in terms of discourse function. Features of problem messages included: frequent use of metaphorical language to describe symptoms, use of or type questions to request advice, and a general lack of direct requests for advice. Advice messages were characterized by casual style and exhibited a variety of discourse patterns with the common function of expressing positive regard and solidarity. The occurrence of these patterns can be related to the special interpersonal needs associated with the discourse function of giving advice. Thanks messages were responses to advice messages, and usually included some expression of thanks for advice, but interestingly, thanks message writers never indicated that they had acted upon or would act upon the advice they received.
Should children be seen and not heard? An examination of how children’s interruptions are treated in family therapy
Authors: O’Reilly Michelle
Published: July 2006

This work adds to the growing literature on children’s talk and the extensive research on interruptions by combining the two. I investigate children in the institutional context of family therapy and their interactions with the parents and therapist. Drawing upon 22 hours of natural family therapy data and four families, I use a discursive approach. I note that children are not attended to when they try to interrupt unless they persist and then the acknowledgement is negative. I show that when the main topic is about extremes of behaviour the child’s none relevant interruption is ignored. There are occasions however when the child interrupts with a topic relevant issue and these are usually attended to. This research has wider implications for therapeutic practice and children’s role in therapy. There is a need for further study of children’s interruptive discourse practice as research in this area is limited.
The growing momentum and legitimacy behind an alliance for international education
Authors: Bunnell Tristan
Published: July 2006

English

Within the diverse universe of internationally minded schools there is currently much momentum behind the creation of some form of ‘alliance’. Although the movement behind this can be traced back to the early 1990s, this article proposes that the current momentum can be largely understood within a fundamental paradigm shift emerging within education generally, towards greater collaboration, networking and partnership. This arguably gives the ‘alliance’ project a much greater deal of legitimacy than has previously been implied. At the same time, a further set of complex factors can be identified within the universe of internationally minded schools.

French

Il existe actuellement une grande aspiration en vue de créer une certaine forme 'd'alliance' au sein de la diversité d'établissements scolaires sensibles à la réalité internationale. Bien que ce mouvement remonte au début des añes 90, cet article suggère que l'impulsion actuelle s'inscrit en grande partie dans le cadre d'une mutation profonde qui voit le jour dans l'éducation en général, en vue de renforcer les collaborations et de développer les réseaux de contacts et les partenariats. Ainsi, ce projet 'd'alliance' a sans doute une plus grande légitimité aujourd'hui qu'on ne le supposait auparavant. Parallèlement, l'article permet d'identifier un ensemble supplémentaire de facteurs complexes au sein des établissements scolaires sensibles à la réalité internationale.

Spanish

En estos momentos, en el universo variopinto de los colegios con orientación internacional, se hace mucho hincapié en crear algún tipo de 'alianza'. Aunque esta tendencia se puede remontar a principios de los años 90, en este estudio se sugiere que se puede comprender esta tendencia en el marco de un cambio de paradigma fundamental que empieza a surgir en el sector de la educación en general. Este cambio consiste en buscar más colaboraciones, redes de contacto y asociaciones, y le da al proyecto de 'alianzas' un grado de legitimidad mayor que el que ten'a anteriormente. Además, dentro del universo de los colegios con orientación internacional, puede identificarse también otro grupo de factores complejos.
The international school industry
Authors: MacDonald James
Published: July 2006

English

Based upon the results of a quantitative analysis of tuition revenues generated by international schools, it is argued that international schools can be examined in terms of a global multi-billion dollar industry and that business theory can be, and is being, applied in international schools today. This article proposes that international schools are organizations with double bottom lines - one educational and one business - and suggests that only by peering through a set of properly aligned educational and business lenses can a true and clear picture of an international school be obtained.

French

D'après les résultats d'une analyse quantitative sur les revenus générés par les frais de scolarité des établissements scolaires internationaux, il apparaîtrait que ces derniers représentent une industrie mondiale se chiffrant en milliers de milliards de dollars américains. En outre, cette théorie commerciale peut s'appliquer, et est même appliquée, dans les établissements scolaires internationaux de nos jours. Cet article suggère que les établissements scolaires internationaux constituent des organisations ayant une double activité; l'une éducative, l'autre commerciale. Il avance également que ce n'est qu'en trouvant un équilibre entre ces deux perspectives que l'on peut avoir une idée précise de ce que représente un établissement scolaire international.

Spanish

Basándose en los resultados de un análisis cuantitativo de los ingresos que generan las tasas de matriculación en los colegios internacionales, este artículo argumenta que los colegios internacionales pueden considerarse una industria mundial valorada en miles de millones de dólares a la que actualmente puede aplicarse, y de hecho se aplica, la teoría empresarial. Sugiere que los colegios internacionales son organizaciones con dos ejes principales, uno educativo y otro empresarial, y que sólo puede obtenerse una impresión clara y realista de un colegio internacional si se analiza desde una perspectiva educativa y una perspectiva empresarial debidamente alineadas.
The CML-related oncoprotein BCR/ABL induces expression of histidine decarboxylase (HDC) and the synthesis of histamine in leukemic cells
Authors: Aichberger Karl J. , Mayerhofer Matthias , Vales Anja , Krauth Maria-Theresa , Gleixner Karoline V. , Bilban Martin , Esterbauer Harald , Sonneck Karoline , Florian Stefan , Derdak Sophia , Pickl Winfried F. , Agis Hermine , Falus Andras , Sillaber Christian , Valent Peter
Published: July 2006

Basophil numbers are typically elevated in chronic myeloid leukemia (CML) and increase during disease progression. Histamine is an essential mediator and marker of basophils and is highly up-regulated in CML. We examined the biochemical basis of histamine synthesis in CML cells. The CML-specific oncoprotein BCR/ABL was found to promote expression of histidine decarboxylase (HDC) and synthesis of histamine in Ba/F3 cells. Moreover, the BCR/ABL tyrosine kinase inhibitors imatinib (STI571) and nilotinib (AMN107) decreased histamine levels and HDC mRNA expression in BCR/ABL-transformed Ba/F3 cells, in the CML-derived basophil cell line KU812, and in primary CML cells. Synthesis of histamine was found to be restricted to the basophil compartment of the CML clone and to depend on signaling through the PI3-kinase pathway. CML cells also expressed histamine receptors (HRs), including HR-1, HR-2, HR-4, and histamine-binding CYP450 isoenzymes which also serve as targets of HR antagonists. The HR-1 antagonists loratadine and terfenadine, which bind to CYP450, were found to counteract proliferation of CML cells, whereas no growth inhibition was observed with the HR-1 antagonist fexofenadine which is not targeted or metabolized by CYP450. Moreover, DPPE, an inhibitor of histamine-binding CYP450 isoenzymes, produced growth inhibition in CML cells. Together, these data show that BCR/ABL promotes histamine production in CML cells and that certain HR-targeting drugs exert antileukemic effects on CML cells.
MicroRNAs modulate the angiogenic properties of HUVECs
Authors: Poliseno Laura , Tuccoli Andrea , Mariani Laura , Evangelista Monica , Citti Lorenzo , Woods Keith , Mercatanti Alberto , Hammond Scott , Rainaldi Giuseppe
Published: July 2006

MicroRNAs (miRNAs) have recently come into focus as key posttranscriptional modulators of gene expression. In this work, we addressed whether in vitro angiogenesis is an miRNA-regulated process. We performed large-scale analysis of miRNA expression in human umbilical vein endothelial cells (HUVECs) and found that 15 highly expressed miRNAs have the receptors of angiogenic factors as putative targets. In particular, we demonstrated that miR-221 and miR-222 affect c-Kit expression and, as a consequence, the angiogenic properties of its ligand stem cell factor. Interaction between miR-222 and c-Kit is likely to be part of a complex circuit that controls the ability of endothelial cells to form new capillaries.
MIP-1α (CCL3) is a downstream target of FGFR3 and RAS-MAPK signaling in multiple myeloma
Authors: Masih-Khan Esther , Trudel Suzanne , Heise Carla , Li Zhihua , Paterson Joshua , Nadeem Vincent , Wei Ellen , Roodman David , Claudio Jaime O. , Bergsagel P. Leif , Stewart A. Keith
Published: July 2006

Overexpression of fibroblast growth factor receptor 3 (FGFR3) is a hallmark of t(4;14) multiple myeloma (MM). To dissect the mechanism of FGFR3 oncogenesis in MM, we used 3 FGFR selective kinase inhibitors—CHIR258, PD173074, and SU5402—and FGFR3-specific siRNA to modulate FGFR3 activity. Conversely, the ligand FGF was used to stimulate FGFR3 function in human MM cells. The transcriptional response to FGFR3 modification was recorded, and gene expression changes common to all 5 modifiers were documented. Ten genes were commonly regulated. Macrophage inflammatory protein-1 alpha (MIP-1α) was the single most differentially altered gene. MIP-1 α promoter function, gene expression, and protein secretion were each down-regulated following inhibition of FGFR3 signaling. Down-regulation of MIP-1 α was not, however, observed following FGFR3 inhibition in MM cells with RAS mutations implicating RAS-MAPK in MIP-1 α regulation. As confirmation, inhibition of ERK1 also down-regulated MIP-1 α in FGFR3 inhibitor-resistant cells harboring RAS mutations. MIP-1 α is implicated in the survival and proliferation of MM cells and the pathogenesis of MM bone disease. Our observation is the first to directly link an initiating IgH translocation not only to MM-cell growth and survival but also to the disease-associated bone disease.
Low SCL/TAL1 expression reveals its major role in adult hematopoietic myeloid progenitors and stem cells
Authors: de la Grange Philippe Brunet , Armstrong Florence , Duval Veronique , Rouyez Marie-Christine , Goardon Nicolas , Romeo Paul-Henri , Pflumio Françoise
Published: July 2006

Stem cell leukemia/T cell acute leukemia 1 (SCL/TAL1) plays a key role in the development of murine primitive hematopoiesis but its functions in adult definitive hematopoiesis are still unclear. Using lentiviral delivery of TAL1-directed shRNA in human hematopoietic cells, we show that decreased expression of TAL1 induced major disorders at different levels of adult hematopoietic cell development. Erythroid and myeloid cell production in cultures was dramatically decreased in TAL1-directed shRNA-expressing cells, whereas lymphoid B-cell development was normal. These results confirm the role of TAL1 in the erythroid compartment and show TLA1's implication in the function of myeloid committed progenitors. Moreover, long-term cultures and transplantation of TAL1-directed shRNA-expressing CD34+ cells into irradiated nonobese diabetic–severe combined immunodeficient (NOD-SCID) mice led to dramatically low levels of human cells of all lineages including the B-lymphoid lineage, strongly suggesting that TAL1 has a role in the early commitment of hematopoietic stem cells (HSCs) in humans. Cultures and transplantation experiments performed with mouse Sca1+ cells gave identical results. Altogether, these observations definitively show that TAL1 participates in the regulation of hematopoiesis from HSCs to myeloid progenitors, and pinpoint TAL1 as a master protein of human and murine adult hematopoiesis.
FcRn: an IgG receptor on phagocytes with a novel role in phagocytosis
Authors: Vidarsson Gestur , Stemerding Annette M. , Stapleton Nigel M. , Spliethoff Suzanne E. , Janssen Hans , Rebers Frank E. , de Haas Masja , van de Winkel Jan G.
Published: July 2006

Here, we report that the MHC class I-related neonatal Fc receptor (FcRn) is expressed within azurophilic and specific granules of neutrophils and relocates to phagolysosomes on phagocytosis of IgG-opsonized bacteria. We found FcRn to enhance phagocytosis in a pH-dependent manner which was independent of IgG recycling. IgG-opsonized bacteria were inefficiently phagocytosed by neutrophils from β2M knock-out or FcRn α-chain knock-out mice, which both lack expression of FcRn. Similarly, low phagocytic activity was also observed with mutated IgG (H435A), which is incapable of binding to FcRn, while retaining normal binding to classical leukocyte Fcγ receptors. Finally, a TAT peptide representing intracellular endocytosis and transport motifs within FcRn strongly inhibited IgG-mediated phagocytosis. These findings support a novel concept in which FcRn fulfills a major role in IgG-mediated phagocytosis.
Impaired neutrophil chemotaxis in sepsis associates with GRK expression and inhibition of actin assembly and tyrosine phosphorylation
Authors: Arraes Sandra Mara A. , Freitas Marta S. , da Silva Simone V. , de Paula Neto Heitor A. , Alves-Filho Jose Carlos , Martins Maria Auxiliadora , Basile-Filho Anibal , Tavares-Murta Beatriz M. , Barja-Fidalgo Christina , Cunha Fernando Q.
Published: July 2006

The deregulation of inflammatory response during sepsis seems to reflect the overproduction of mediators, which suppress leukocyte functions. We investigated the intracellular mechanisms underlying the inability of neutrophils from severe septic patients to migrate toward chemoattractants. Patients with sepsis (52) and 15 volunteers were prospectively enrolled. Patients presented increased circulating levels of tumor necrosis factor-α, interferon-γ, interleukin (IL)–8, and IL-10. Patients showed reduced neutrophil chemotaxis to formyl-methionyl-leucyl-phenylalanine (FMLP), leukotriene B4 (LTB4) or IL-8. No difference in the transcription or expression of the IL-8 receptor, CXCR1, was detected in neutrophils from controls and patients. However, septic neutrophils failed to increase tyrosine phosphorylation and actin polymerization in response to IL-8 or LTB4. In contrast, septic neutrophils, similar to controls, showed phagocytic activity that induced actin polymerization and augmented phosphotyrosine content. Treatment of control neutrophils with cytokines and lipopolysaccharide (LPS) to mimic endogenous septic environment inhibited actin polymerization and tyrosine phosphorylation in response to IL-8 or LTB4. High expression of G protein–coupled receptor kinase 2 (GRK2) and GRK5 was detected in septic neutrophils and control cells treated with cytokines plus LPS. Data suggest that endogenous mediators produced during sepsis might continually activate circulating neutrophils, leading to GRK activation, which may induce neutrophil desensitization to chemoattractants.
HEX expression and localization in normal mammary gland and breast carcinoma
Authors: Puppin Cinzia , Puglisi Fabio , Pellizzari Lucia , Manfioletti Guidalberto , Pestrin Marta , Pandolfi Maura , Piga Andrea , Di Loreto Carla , Damante Giuseppe
Published: July 2006

Background

The homeobox gene HEX is expressed in several cell types during different phases of animal development. It encodes for a protein localized in both the nucleus and the cytoplasm. During early mouse development, HEX is expressed in the primitive endoderm of blastocyst. Later, HEX is expressed in developing thyroid, liver, lung, as well as in haematopoietic progenitors and endothelial cells. Absence of nuclear expression has been observed during neoplastic transformation of the thyroid follicular cells. Aim of the present study was to evaluate the localization and the function of the protein HEX in normal and tumoral breast tissues and in breast cancer cell lines.

Methods

HEX expression and nuclear localization were investigated by immunohistochemistry in normal and cancerous breast tissue, as well as in breast cancer cell lines. HEX mRNA levels were evaluated by real-time PCR. Effects of HEX expression on Sodium Iodide Symporter (NIS) gene promoter activity was investigated by HeLa cell transfection.

Results

In normal breast HEX was detected both in the nucleus and in the cytoplasm. In both ductal and lobular breast carcinomas, a great reduction of nuclear HEX was observed. In several cells from normal breast tissue as well as in MCF-7 and T47D cell line, HEX was observed in the nucleolus. MCF-7 treatment with all-trans retinoic acid enhanced HEX expression and induced a diffuse nuclear localization. Enhanced HEX expression and diffuse nuclear localization were also obtained when MCF-7 cells were treated with inhibitors of histone deacetylases such as sodium butyrate and trichostatin A. With respect to normal non-lactating breast, the amount of nuclear HEX was greatly increased in lactating tissue. Transfection experiments demonstrated that HEX is able to up-regulate the activity of NIS promoter.

Conclusion

Our data indicate that localization of HEX is regulated in epithelial breast cells. Since modification of localization occurs during lactation and tumorigenesis, we suggest that HEX may play a role in differentiation of the epithelial breast cell.
NERVE: New Enhanced Reverse Vaccinology Environment
Authors: Vivona Sandro , Bernante Filippo , Filippini Francesco
Published: July 2006

Background

Since a milestone work on Neisseria meningitidis B, Reverse Vaccinology has strongly enhanced the identification of vaccine candidates by replacing several experimental tasks using in silico prediction steps. These steps have allowed scientists to face the selection of antigens from the predicted proteome of pathogens, for which cell culture is difficult or impossible, saving time and money. However, this good example of bioinformatics-driven immunology can be further developed by improving in silico steps and implementing biologist-friendly tools.

Results

We introduce NERVE (New Enhanced Reverse Vaccinology Environment), an user-friendly software environment for the in silico identification of the best vaccine candidates from whole proteomes of bacterial pathogens. The software integrates multiple robust and well-known algorithms for protein analysis and comparison. Vaccine candidates are ranked and presented in a html table showing relevant information and links to corresponding primary data. Information concerning all proteins of the analyzed proteome is not deleted along selection steps but rather flows into an SQL database for further mining and analyses.

Conclusion

After learning from recent years' works in this field and analysing a large dataset, NERVE has been implemented and tuned as the first available tool able to rank a restricted pool (~8–9% of the whole proteome) of vaccine candidates and to show high recall (~75–80%) of known protective antigens. These vaccine candidates are required to be "safe" (taking into account autoimmunity risk) and "easy" for further experimental, high-throughput screening (avoiding possibly not soluble antigens). NERVE is expected to help save time and money in vaccine design and is available as an additional file with this manuscript; updated versions will be available at http://www.bio.unipd.it/molbinfo.
Methylation mediated silencing of TMS1/ASC gene in prostate cancer
Authors: Das Partha M , Ramachandran Kavitha , VanWert Jane , Ferdinand Larry , Gopisetty Gopal , Reis Isildinha M , Singal Rakesh
Published: July 2006

Background

Transcriptional silencing associated with aberrant promoter methylation has been established as an alternate pathway for the development of cancer by inactivating tumor suppressor genes. TMS1 (Target of Methylation induced Silencing), also known as ASC (Apoptosis Speck like protein containing a CARD) is a tumor suppressor gene which encodes for a CARD (caspase recruitment domain) containing regulatory protein and has been shown to promote apoptosis directly and by activation of downstream caspases. This study describes the methylation induced silencing of TMS1/ASC gene in prostate cancer cell lines. We also examined the prevalence of TMS1/ASC gene methylation in prostate cancer tissue samples in an effort to correlate race and clinico-pathological features with TMS1/ASC gene methylation.

Results

Loss of TMS1/ASC gene expression associated with complete methylation of the promoter region was observed in LNCaP cells. Gene expression was restored by a demethylating agent, 5-aza-2'deoxycytidine, but not by a histone deacetylase inhibitor, Trichostatin A. Chromatin Immunoprecipitation (ChIP) assay showed enrichment of MBD3 (methyl binding domain protein 3) to a higher degree than commonly associated MBDs and MeCP2. We evaluated the methylation pattern in 66 prostate cancer and 34 benign prostatic hyperplasia tissue samples. TMS1/ASC gene methylation was more prevalent in prostate cancer cases than controls in White patients (OR 7.6, p 0.002) while no difference between the cases and controls was seen in Black patients (OR 1.1, p 0.91).

Conclusion

Our study demonstrates that methylation-mediated silencing of TMS1/ASC is a frequent event in prostate cancer, thus identifying a new potential diagnostic and prognostic marker for the treatment of the disease. Racial differences in TMS1/ASC methylation patterns implicate the probable role of molecular markers in determining in susceptibility to prostate cancer in different ethnic groups.
Parameter estimation in biochemical systems models with alternating regression
Authors: Chou I-Chun , Martens Harald , Voit Eberhard O
Published: July 2006

Background

The estimation of parameter values continues to be the bottleneck of the computational analysis of biological systems. It is therefore necessary to develop improved methods that are effective, fast, and scalable.

Results

We show here that alternating regression (AR), applied to S-system models and combined with methods for decoupling systems of differential equations, provides a fast new tool for identifying parameter values from time series data. The key feature of AR is that it dissects the nonlinear inverse problem of estimating parameter values into iterative steps of linear regression. We show with several artificial examples that the method works well in many cases. In cases of no convergence, it is feasible to dedicate some computational effort to identifying suitable start values and search settings, because the method is fast in comparison to conventional methods that the search for suitable initial values is easily recouped. Because parameter estimation and the identification of system structure are closely related in S-system modeling, the AR method is beneficial for the latter as well. Specifically, we show with an example from the literature that AR is three to five orders of magnitudes faster than direct structure identifications in systems of nonlinear differential equations.

Conclusion

Alternating regression provides a strategy for the estimation of parameter values and the identification of structure and regulation in S-systems that is genuinely different from all existing methods. Alternating regression is usually very fast, but its convergence patterns are complex and will require further investigation. In cases where convergence is an issue, the enormous speed of the method renders it feasible to select several initial guesses and search settings as an effective countermeasure.
Arbidol: a broad-spectrum antiviral that inhibits acute and chronic HCV infection
Authors: Boriskin Yury S , Pécheur Eve-Isabelle , Polyak Stephen J
Published: July 2006

Arbidol (ARB) is an antiviral compound that was originally proven effective for treatment of influenza and several other respiratory viral infections. The broad spectrum of ARB anti-viral activity led us to evaluate its effect on hepatitis C virus (HCV) infection and replication in cell culture. Long-term ARB treatment of Huh7 cells chronically replicating a genomic length genotype 1b replicon resulted in sustained reduction of viral RNA and protein expression, and eventually cured HCV infected cells. Pre-treatment of human hepatoma Huh7.5.1 cells with 15 μM ARB for 24 to 48 hours inhibited acute infection with JFH-1 virus by up to 1000-fold. The inhibitory effect of ARB on HCV was not due to generalized cytotoxicity, nor to augmentation of IFN antiviral signaling pathways, but involved impaired virus-mediated membrane fusion. ARB's affinity for membranes may inhibit several aspects of the HCV lifecycle that are membrane-dependent.
The psychological well-being of children orphaned by AIDS in Cape Town, South Africa
Authors: Cluver Lucie , Gardner Frances
Published: July 2006

Background

An estimated 2 million children are parentally bereaved by AIDS in South Africa. Little is known about mental health outcomes for this group.

Methods

This study aimed to investigate mental health outcomes for urban children living in deprived settlements in Cape Town. 30 orphaned children and 30 matched controls were compared using standardised questionnaires (SDQ) on emotional and behavioural problems, peer and attention difficulties, and prosocial behaviour. The orphan group completed a modified version of a standardised questionnaire (IES-8), measuring Post-Traumatic Stress symptoms. Group differences were tested using t-tests and Pearson's chi-square.

Results

Both groups scored highly for peer problems, emotional problems and total scores. However, orphans were more likely to view themselves as having no good friends (p = .002), to have marked concentration difficulties (p = .03), and to report frequent somatic symptoms (p = .05), but were less likely to display anger through loss of temper (p = .03). Orphans were more likely to have constant nightmares (p = .01), and 73% scored above the cut-off for Post-Traumatic Stress Disorder.

Conclusion

Findings suggest important areas for larger-scale research for parentally-bereaved children.
Leukocytes, inflammation, and angiogenesis in cancer: fatal attractions
Authors: Rüegg Curzio
Published: July 2006

Leukocytes are cells of defense. Their main function is to protect our body against invading microorganisms. Some leukocytes, in particular, polymorphonuclear and monocytes, accumulate at sites of infection and neutralize pathogens through innate mechanisms. The blood and lymphatic vascular system are essential partners in this defensive reaction: Activated endothelial cells promote leukocyte recruitment at inflammatory sites; new blood vessel formation, a process called angiogenesis, sustains chronic inflammation, and lymphatic vessels transport antigens and antigen-presenting cells to lymph nodes, where they stimulate naive T and B lymphocytes to elicit an antigen-specific immune response. In contrast, leukocytes and lymphocytes are far less efficient in protecting us from cancer, the “enemy from within.” Worse, cancer can exploit inflammation to its advantage. The role of angiogenesis, leukocytes, and inflammation in tumor progression was discussed at the second Monte Verità Conference, Tumor Host Interaction and Angiogenesis: Basic Mechanisms and Therapeutic Perspectives, held in Ascona, Switzerland, October 1–5, 2005. (Conference chairs were K. Alitalo, M. Aguet, C. Rüegg, and I. Stamenkovic.) Eight articles reporting about topics presented at the conference are featured in this issue of the Journal of Leukocyte Biology.
Stress System Activity, Innate and T Helper Cytokines, and Susceptibility to Immune‐Related Diseases
Authors: CALCAGNI EMANUELE , ELENKOV ILIA
Published: July 2006

Abstract:  Associations between stress and health outcomes have now been carefully documented, but the mechanisms by which stress specifically influences disease susceptibility and outcome remain poorly understood. Recent evidence indicates that glucocorticoids (GCs) and catecholamines (CAs), the major stress hormones, inhibit systemically IL‐12, TNF‐α, and INF‐γ, but upregulate IL‐10, IL‐4, and TGF‐β production. Thus, during an immune and inflammatory response, the activation of the stress system, through induction of a Th2 shift may protect the organism from systemic “overshooting” with T helper lymphocyte 1 (Th1)/proinflammatory cytokines. In certain local responses and under certain conditions, however, stress hormones may actually facilitate inflammation, through induction of IL‐1, IL‐6, IL‐8, IL‐18, TNF‐α, and CRP production, and through activation of the corticotropin‐releasing hormone (CRH)/substance P(SP)‐histamine axis. Autoimmunity, chronic infections, major depression, and atherosclerosis are characterized by a dysregulation of the pro/anti‐inflammatory and Th1/Th2 cytokine balance. Thus, hyperactive or hypoactive stress system, and a dysfunctional neuroendocrine–immune interface associated with abnormalities of the “systemic anti‐inflammatory feedback” and/or “hyperactivity” of the local proinflammatory factors may contribute to the pathogenesis of these diseases. Conditions that are associated with significant changes in stress system activity, such as acute or chronic stress, cessation of chronic stress, pregnancy and the postpartum period, or rheumatoid arthritis (RA) through modulation of the systemic or local pro/anti‐inflammatory and Th1/Th2 cytokine balance, may suppress or potentiate disease activity and/or progression. Thus, stress hormones‐induced inhibition or upregulation of innate and Th cytokine production may represent an important mechanism by which stress affects disease susceptibility, activity, and outcome of various immune‐related diseases.
Prolactin and Growth Hormone Responses to Hypoglycemia in Patients with Systemic Sclerosis and Psoriatic Arthritis
Authors: ROVENSKY JOZEF , RAFFAYOVA HELENA , IMRICH RICHARD , RADIKOVA ZOFIA , PENESOVA ADELA , MACHO LADISLAV , LUKAC JOZEF , MATUCCI‐CERINIC MARCO , VIGAS MILAN
Published: July 2006

Abstract: This study compared prolactin (PRL) and growth hormone (GH) responses to hypoglycemia in premenopausal females with systemic sclerosis (SSc) and psoriatic arthritis (PsA) with those in matched healthy controls. No differences were found in glucose and GH responses to hypoglycemia in both groups of patients compared to controls. SSc patients had lower PRL response (P< 0.05) to hypoglycemia compared to controls. PRL response tended to be lower also in PsA patients, however the difference did not reach level of statistical significance (P= 0.11). The present study showed decreased PRL response to hypoglycemia in premenopausal females with SSc.
Neurogenic Inflammation and Arthritis
Authors: LEVINE JON D. , KHASAR SACHIA G. , GREEN PAUL G.
Published: July 2006

Abstract: Inflammation and inflammatory diseases are sexually dimorphic, but the underlying causes for this observed sexual dimorphism are poorly understood. We discuss neural‐immune mechanisms that underlie sexual dimorphism in three critical aspects of the inflammatory process—plasma extravasation, neutrophil function, and inflammatory hyperalgesia. Plasma extravasation and accumulation/activation of leukocytes into tissues are critical components in inflammation and are required for several other aspects of the inflammatory response. Pain (hyperalgesia) also markedly influences the magnitude of other components of the inflammatory response and induces a feedback control of plasma extravasation and neutrophil function. More important, this feedback control itself is powerfully modulated by vagal afferent activity and both the function of the primary afferent nociceptor and the modulation of inflammatory hyperalgesia by vagal afferent activity are highly sexually dimorphic.
Epidemiological Aspects of Rheumatoid Arthritis
Authors: KVIEN TORE K. , UHLIG TILL , ØDEGÅRD SIGRID , HEIBERG MARTE S.
Published: July 2006

Abstract:  Many rheumatic diseases, including rheumatoid arthrits (RA) are more frequent in females than males. The objective of this article was to examine the female versus male perspective regarding prevalence/incidence, etiological factors, disease severity/outcomes, access to therapy and therapeutic responses. We also present results from some new analyses from the patient registers in Oslo to supplement existing literature in this area. We found that the prevalence of RA is higher in females than males, the incidence is 4–5 times higher below the age of 50, but above 60–70 years the female/male ratio is only about 2. Smoking is a consistent predictor of RA in males, but findings have been more inconsistent in females. We could not confirm that health status is worse in females than males when corrections were made for different disease duration and for the underlying tendency of healthy females to report worse subjective health status than males. Some studies and data presented here indicate that females have less access to health services. We also found that female sex reduces the likelihood of achiving treatment response with methotrexate and anti‐tumor necrosis factor (anti‐TNF) drugs by 30–50%. More research is needed to fully describe the differences between males and females regarding epidemiological data.
Sex Hormones and Risks of Rheumatoid Arthritis and Developmental or Environmental Influences
Authors: MASI ALFONSE T. , ALDAG JEAN C. , CHATTERTON ROBERT T
Published: July 2006

Abstract:  Sex hormone relationships for onset risks of rheumatoid arthritis (RA) were analyzed in a nested case–control study, derived from a large community‐based prospective cohort. A self‐reported history of RA in a first‐degree relative, heavy cigarette smoking, and positive rheumatoid factor (RF) were confirmed predictors of subsequent RA onset in this data set. In the 11 premenopausal onset cases, lower serum dehydroepiandrosterone sulfate levels were observed as was an imbalance in serum IL‐1β to IL‐1ra levels; the latter was not observed in the 43 controls (CNs). In the 18 male cases, significantly higher serum cortisol was observed in the six cases with positive family history versus the 12 with a negative history. To the contrary, a small minority of the male cases had combined low serum cortisol and testosterone, which was not observed in the 72 CNs. Significant gender dimorphism was observed between the sex hormones and serum log RF titers as well as in the correlations of serum log testosterone and estradiol. Principal component analysis of multiply‐imputed data sets extracted four uncorrelated components, which provided concordant neuroendocrine immune relationships to the previously investigated univariate and multivariate analyses. The literature on developmental and environmental influences on sex hormones and risks of RA was reviewed.
Androgen and Prolactin (Prl) Levels in Systemic Sclerosis (SSc)
Authors: MIRONE LUISA , BARINI ANGELA , BARINI ANTONELLA
Published: July 2006

Abstract:  Testosterone (T), sex hormone‐binding globulin, (SHBG), dehydroepiandrosterone sulfate (DHEAS), and prolactin (Prl) serum levels were measured by electrochemiluminescense immunoassay (ECLIA) in 39 patients with systemic sclerosis (SSc) and compared with serum hormonal levels in control subjects matched for sex and reproductive status. A possible relationship with disease duration and disease severity was examined. Our data show an altered androgen and prolactin (Prl) status in SSc patients, in most cases related to disease duration and disease severity score. We can hypothesize that hormonal dysregulation is a consequence of the chronicity of the disease. The altered hormonal status could result in relative immunological hyperactivity contributing to enhance tissue damage and disease severity.
Autoimmunity and Pregnancy
Authors: TINCANI ANGELA , NUZZO MONICA , MOTTA MARIO , ZATTI SONIA , LOJACONO ANDREA , FADEN DAVID
Published: July 2006

Abstract:  In women who suffer from rheumatic diseases (RDs) the risk of repeated fetal loss, intrauterine growth restriction, and preterm birth remains higher than in the general population. Antiphospholipid antibodies are frequently observed in patients with systemic lupus erythematosus (SLE). They are associated with recurrent pregnancy losses that may occur at any age of gestation. The cause of fetal death is believed to be intraplacental thrombosis, although other pathologic mechanisms have been described. A recent study has described the increased frequency of learning disabilities in the offspring of SLE patients; case reports of neonatal thrombosis are very rare. Transplacental passage of IgG anti‐Ro/SS‐A antibodies is linked to neonatal lupus (2%). The main manifestation is congenital heart block (CHB) due to the binding of anti‐Ro/SS‐A antibodies to cardiac conduction tissue and to the consequent inflammatory/fibroid reaction. Neonatal lupus also includes cutaneous, hematologic, and hepatobiliary manifestations, which are typically transient. Incomplete CHB can be treated with fluorinated corticosteroids to prevent the progression and decrease inflammation. Intravenous immunoglobulin, decreasing the tranplacental passage of anti‐Ro/SS‐A, has been proposed as prophylactic therapy in patients who had one or more child with CHB. Transplacental passage of antiplatelet antibodies, in about 10% of mothers with SLE, can induce thrombocytopenia in the fetus or the neonate. Patients with RD have a higher incidence of anxiety and depression compared to the general population, interfering with parenthood and the upbringing of children.
Cytokines and Pregnancy in Rheumatic Disease
Authors: ØSTENSEN MONIKA , FÖRGER FRAUKE , VILLIGER PETER M.
Published: July 2006

Abstract:  Cytokines are important mediators involved in the successful outcome of pregnancy. The concept of pregnancy as biased toward a Th2 immune response states that Th1 type cytokines are associated with pregnancy failure and that Th2 cytokines are protective and counteract pregnancy‐related disorders. Studies at the level of the maternal–fetal interface, in the maternal circulation and in cells of peripheral blood have shown that the Th2 concept of pregnancy is an oversimplification. Both Th1 and Th2 type cytokines play a role at different stages of pregnancy and are adapted to the localization and function of cells and tissues. The changes of local and systemic cytokine patterns during pregnancy correspond to neuroendocrine changes with hormones as powerful modulators of cytokine expression. Several autoimmune disorders show a modulation of disease activity during and after pregnancy. In rheumatic diseases with a predominance of a Th1 immune response, a shift to a Th2 type immune response during pregnancy has been regarded as beneficial. Studies of pregnant patients with rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE) have shown a cytokine expression similar to that found in healthy pregnant women. Significant differences were present only for a few cytokines and seemed related to the activity of the underlying disease. Interestingly, a gestational increase of cytokine inhibitors interleukin 1 receptor antagonist (IL‐1ra) and soluble tumor necrosis factor receptor (sTNFR) in the circulation corresponded to low disease activity in RA. The influence of hormones and cytokines on autoimmune disease is an issue for further study.