bluuebunny/crossref_metadata_2025 huggingface dataset:
Most CML patients who have a suboptimal response to imatinib have low OCT-1 activity: higher doses of imatinib may overcome the negative impact of low OCT-1 activity
Authors: White Deborah L. , Saunders Verity A. , Dang Phuong , Engler Jane , Venables Amity , Zrim Stephanie , Zannettino Andrew , Lynch Kevin , Manley Paul W. , Hughes Timothy
Published: August 2007

Interpatient variability in intracellular uptake and retention (IUR) of imatinib may be due to variable function of the OCT-1 influx pump. OCT-1 activity was measured in pretherapy blood from chronic myeloid leukemia (CML) patients by calculating the difference in IUR of [14C]-imatinib with and without OCT-1 inhibition. Of patients with higher than median (high) OCT-1 activity, 85% achieved major molecular response (MMR) by 24 months, versus 45% with no more than a median (low) OCT-1 activity. Assessing patients receiving 600 mg imatinib per day and those averaging fewer than 600 mg over 12 months of therapy revealed patients with high OCT-1 activity achieved excellent molecular response regardless of dose, whereas response of patients with low OCT-1 activity was highly dose dependent. Of patients with low OCT-1 activity who received fewer than 600 mg, 45% failed to achieve a 2-log reduction by 12 months, and 82% failed to achieve a MMR by 18 months, compared with 8% and 17% in the cohort with high OCT-1 activity and dose less than 600 mg/day (P = .017 and P = .022). OCT-1 activity is an important determinant of molecular response to imatinib, with predictive value closely linked to dose. This pretherapy assay identifies patients at greatest risk of suboptimal response where dose intensity is critical, and those likely to respond equally well to standard dose imatinib.
Lymphatic reprogramming of microvascular endothelial cells by CEA-related cell adhesion molecule-1 via interaction with VEGFR-3 and Prox1
Authors: Kilic Nerbil , Oliveira-Ferrer Leticia , Neshat-Vahid Samira , Irmak Ster , Obst-Pernberg Kirstin , Wurmbach Jan-Henner , Loges Sonja , Kilic Ergin , Weil Joachim , Lauke Heidrun , Tilki Derya , Singer Bernhard B. , Ergün Süleyman
Published: August 2007

Here, we demonstrate that carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is expressed and co-localized with podoplanin in lymphatic endothelial cells (LECs) of tumor but not of normal tissue. CEACAM1 overexpression in human dermal microvascular endothelial cells (HDMECs) results in a significant increase of podoplanin-positive cells in fluorescence-activated cell sorting analyses, while such effects are not observed in CEACAM1 overexpressing human umbilical vein endothelial cell (HUVECs). This effect of CEACAM1 is ceased when HDMECs are transfected with CEACAM1/y− missing the tyrosine residues in its cytoplasmic domain. CEACAM1 overexpression in HDMECs leads to an up-regulation of vascular endothelial growth factor C, -D (VEGF-C, -D) and their receptor vascular endothelial growth factor receptor 3 (VEGFR-3) at mRNA and protein levels. HDMECs transfected with CEACAM1 but not those with CEACAM1/y− show enhanced expression of the lymphatic markers Prox1, podoplanin, and LYVE-1. Furthermore, Prox1 silencing in HDMECs via small interfering RNA blocks the CEACAM1-induced increase of VEGFR-3 expression. Number and network of endothelial tubes induced by VEGF-C and -D are enhanced in CEACAM1-overexpressing HDMECs. Moreover, VEGF-A treatment of CEACAM1-silenced HDMECs restores their survival but not that with VEGF-C and VEGF-D. These data imply that the interaction of CEACAM1 with Prox1 and VEGFR-3 plays a crucial role in tumor lymphangiogenesis and reprogramming of vascular endothelial cells to LECs. CEACAM1-induced signaling effects appear to be dependent on the presence of tyrosine residues in the CEACAM1 cytoplasmic domain.
Nonpharmacological and pharmacological interventions to prevent or reduce airway remodelling
Authors: Walters E. H. , Reid D. W. , Johns D. P. , Ward C.
Published: August 2007

In the present review of airway remodelling and its response to therapies, clinical observations about airway physiological abnormalities, assumed to be caused by remodelling processes, are related to what is known about the components of structural changes from airway sampling and histopathological analysis. The review focuses on three important diseases: asthma, chronic obstructive pulmonary disease and bronchiolitis obliterans syndrome (BOS), which occurs commonly after lung transplantation as a manifestation of chronic rejection. The present authors chose to use BOS as an issue, because with routine bronchoscopic surveillance after lung transplantation there has been more opportunity to directly study airway pathology longitudinally than in more everyday conditions. In addition, the present authors have reviewed animal models of induced airway remodelling, where most information is available on the potential of therapeutic intervention. Finally, the limited information that can be gained from the literature on the effects of commonly used airway medications on remodelling components is reviewed. In conclusion, the present authors have detailed some of the gaps in knowledge surrounding the potential to improve or modulate remodelling processes in human disease. The areas where it is believed urgent research needs to be focused have also been highlighted.
Educational intervention decreases exhaled nitric oxide in farmers with occupational asthma
Authors: Dressel H. , Gross C. , de la Motte D. , Sültz J. , Jörres R. A. , Nowak D.
Published: August 2007

Allergic occupational asthma is frequent in farming populations. As educational interventions can improve disease management, the short-term effect of an educational intervention in asthmatic farmers was evaluated on the basis of spirometric indices and exhaled nitric oxide fraction (FeNO).

Farmers with occupational asthma (n = 81), mostly sensitised against cow dander and storage mites, participated in a 1-day educational programme. Outcome measures were assessed at baseline and after 4–6 weeks, usingFeNO, lung function and a questionnaire. Results were compared with those of a control group without intervention (n = 24).

In the educational group, the proportion of subjects reporting work-related symptoms was reduced after the intervention. TheFeNOdecreased from a geometric mean of 28.2 to 25.7 ppb, and, in subjects with an elevated (>35 ppb) baselineFeNO(n = 32), from 59.7 to 49.2 ppb. The corresponding changes in the control group were 25.6versus27.7 ppb and 49.5versus48.1 ppb. Spirometric results were unaltered in the two groups.

Thus exhaled nitric oxide fraction, a marker of allergic airway inflammation, indicated a beneficial effect of a short-term educational intervention in farmers with occupational asthma. This suggests a potential for exhaled nitric oxide fraction in assessing the efficacy of preventive measures within a short time with higher sensitivity than spirometry.
Unusual cystic presentation of pulmonary nodular amyloidosis associated with MALT-type lymphoma
Authors: Lantuejoul S. , Moulai N. , Quetant S. , Brichon P. Y. , Brambilla C. , Brambilla E. , Ferretti G. R.
Published: August 2007

The case reported herein consists of nodular pulmonary amyloidosis presenting with unusual cystic radiological features which reveal a pulmonary localisation of an extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma).

The present case is the first to report a radiological presentation of nodular pulmonary amyloidosis in the absence of Sjögren's syndrome.

Although transthoracic fine-needle biopsy was helpful for the diagnostic of amyloidosis, final diagnosis of associated MALT-type lymphoma required an open lung biopsy.

This emphasises the importance of performing surgical investigations in pulmonary nodular amyloidosis in order to depict the presence of underlying lung tumours or lymphoproliferative disorders.
Optimization of filtering criterion for SEQUEST database searching to improve proteome coverage in shotgun proteomics
Authors: Jiang Xinning , Jiang Xiaogang , Han Guanghui , Ye Mingliang , Zou Hanfa
Published: August 2007

Background

In proteomic analysis, MS/MS spectra acquired by mass spectrometer are assigned to peptides by database searching algorithms such as SEQUEST. The assignations of peptides to MS/MS spectra by SEQUEST searching algorithm are defined by several scores including Xcorr, ΔCn, Sp, Rsp, matched ion count and so on. Filtering criterion using several above scores is used to isolate correct identifications from random assignments. However, the filtering criterion was not favorably optimized up to now.

Results

In this study, we implemented a machine learning approach known as predictive genetic algorithm (GA) for the optimization of filtering criteria to maximize the number of identified peptides at fixed false-discovery rate (FDR) for SEQUEST database searching. As the FDR was directly determined by decoy database search scheme, the GA based optimization approach did not require any pre-knowledge on the characteristics of the data set, which represented significant advantages over statistical approaches such as PeptideProphet. Compared with PeptideProphet, the GA based approach can achieve similar performance in distinguishing true from false assignment with only 1/10 of the processing time. Moreover, the GA based approach can be easily extended to process other database search results as it did not rely on any assumption on the data.

Conclusion

Our results indicated that filtering criteria should be optimized individually for different samples. The new developed software using GA provides a convenient and fast way to create tailored optimal criteria for different proteome samples to improve proteome coverage.
The PhenoGen Informatics website: tools for analyses of complex traits
Authors: Bhave Sanjiv V , Hornbaker Cheryl , Phang Tzu L , Saba Laura , Lapadat Razvan , Kechris Katherina , Gaydos Jeanette , McGoldrick Daniel , Dolbey Andrew , Leach Sonia , Soriano Brian , Ellington Allison , Ellington Eric , Jones Kendra , Mangion Jonathan , Belknap John K , Williams Robert W , Hunter Lawrence E , Hoffman Paula L , Tabakoff Boris
Published: August 2007

Background

With the advent of "omics" (e.g. genomics, transcriptomics, proteomics and phenomics), studies can produce enormous amounts of data. Managing this diverse data and integrating with other biological data are major challenges for the bioinformatics community. Comprehensive new tools are needed to store, integrate and analyze the data efficiently.

Description

The PhenoGen Informatics website http://phenogen.uchsc.edu is a comprehensive toolbox for storing, analyzing and integrating microarray data and related genotype and phenotype data. The site is particularly suited for combining QTL and microarray data to search for "candidate" genes contributing to complex traits. In addition, the site allows, if desired by the investigators, sharing of the data. Investigators can conduct "in-silico" microarray experiments using their own and/or "shared" data.

Conclusion

The PhenoGen website provides access to tools that can be used for high-throughput data storage, analyses and interpretation of the results. Some of the advantages of the architecture of the website are that, in the future, the present set of tools can be adapted for the analyses of any type of high-throughput "omics" data, and that access to new tools, available in the public domain or developed at PhenoGen, can be easily provided.
Socioeconomic status and hospitalization in the very old: a retrospective study
Authors: Antonelli-Incalzi Raffaele , Ancona Carla , Forastiere Francesco , Belleudi Valeria , Corsonello Andrea , Perucci Carlo A
Published: August 2007

Background

Socioeconomic status could affect the demand for hospital care. The aim of the present study was to assess the role of age, socioeconomic status and comorbidity on acute hospital admissions among elderly.

Methods

We retrospectively examined the discharge abstracts data of acute care hospital admissions of residents in Rome aged 75 or more years in the period 1997–2000. We used the Hospital Information System of Rome, the Tax Register, and the Population Register of Rome for socio-economic data. The rate of hospitalization, modified Charlson's index of comorbidity, and level of income in the census tract of residence were obtained. Rate ratios and 95% confidence limits were computed to assess the relationship between income deciles and rate of hospitalization. Cross-tabulation was used to explore the distribution of the index of comorbidity by deciles of income. Analyses were repeated for patients grouped according to selected diseases.

Results

Age was associated with a marginal increase in the rate of hospitalization. However, the hospitalization rate was inversely related to income in both sexes. Higher income was associated with lower comorbidity. The same associations were observed in patients admitted with a principal diagnosis of chronic condition (diabetes mellitus, heart failure, chron obstructive pulmonary disease) or stroke, but not hip fracture.

Conclusion

Lower social status and associated comorbidity, more than age per se, are associated with a higher rate of hospitalization in very old patients.
Anteroposterior glide versus rotating platform low contact stress (LCS) knee arthroplasty: a randomised controlled trial
Authors: Walley Gayle , Datir Sandeep , Sayana Murali , Rahmatalla Aziz , Dos Remedios Ian , Wynn-Jones Charles , Bridgman Stephen , Maffulli Nicola
Published: August 2007

Background

Fifty thousand knee replacements are performed annually in the UK at an estimated cost of £150 million. Post-operative improvement depends on a number of factors including implant design and patient associated factors. To our knowledge there are no published study's comparing the results of AP glide and rotating platform designs of LCS knee arthroplasty. Therefore we feel that a study is required to investigate and compare the effects of two types of LCS total knee arthroplasty on joint proprioception and range of motion.

Methods/Design

Patients will be randomised to receive either a LCS AP glide or Rotating platform prosthesis. Clinical scores (Oxford knee score, American knee society score, EuroQol), range of motion and proprioception will be assessed prior to and at 3,6, 12 and 24 months after the operation. Proprioception will be assessed in terms of absolute error angle (mean difference between the target angle and the response angle). Knee angles will be measured in degrees using an electromagnetic tracking device, Polhemus 3Space Fastrak that detects positions of sensors placed on the test limb. Student's t-test will be used to compare the mean of two groups.

Discussion

Evidence is lacking concerning the best prosthesis to use for patients undergoing total knee replacement. This pragmatic randomised trial will test the null hypothesis that anteroposterior glide LCS knee arthroplasty does not result in better post operative knee motion and proprioception as compared to rotating platform LCS knee.

Trial Registration

ISRCTN52943804
Physicians' views on resource availability and equity in four European health care systems
Authors: Hurst Samia A , Forde Reidun , Reiter-Theil Stella , Slowther Anne-Marie , Perrier Arnaud , Pegoraro Renzo , Danis Marion
Published: August 2007

Background

In response to limited resources, health care systems have adopted diverse cost-containment strategies and give priority to differing types of interventions. The perception of physicians, who witness the effects of these strategies, may provide useful insights regarding the impact of system-wide priority setting on access to care.

Methods

We conducted a cross-sectional survey to ascertain generalist physicians' perspectives on resources allocation and its consequences in Norway, Switzerland, Italy and the UK.

Results

Survey respondents (N = 656, response rate 43%) ranged in age from 28–82, and averaged 25 years in practice. Most respondents (87.7%) perceived some resources as scarce, with the most restrictive being: access to nursing home, mental health services, referral to a specialist, and rehabilitation for stroke. Respondents attributed adverse outcomes to scarcity, and some respondents had encountered severe adverse events such as death or permanent disability. Despite universal coverage, 45.6% of respondents reported instances of underinsurance. Most respondents (78.7%) also reported some patient groups as more likely than others to be denied beneficial care on the basis of cost. Almost all respondents (97.3%) found at least one cost-containment policy acceptable. The types of policies preferred suggest that respondents are willing to participate in cost-containment, and do not want to be guided by administrative rules (11.2%) or restrictions on hospital beds (10.7%).

Conclusion

Physician reports can provide an indication of how organizational factors may affect availability and equity of health care services. Physicians are willing to participate in cost-containment decisions, rather than be guided by administrative rules. Tools should be developed to enable physicians, who are in a unique position to observe unequal access or discrimination in their health care environment, to address these issues in a more targeted way.
Effect of a restrictive transfusion strategy on transfusion-attributable severe acute complications and costs in the US ICUs: a model simulation
Authors: Zilberberg Marya D , Shorr Andrew F
Published: August 2007

Background

Nearly half of all patients in the Intensive Care Unit (ICU) receive red blood cell (pRBC) transfusions (TFs), despite their associated complications. Restrictive transfusion strategy (Hemoglobin [Hb] < 7 g/dL) has been shown to reduce TF exposure. We estimated the potential annual reduction in transfusion-attributable severe acute complications (TSACs) and costs across the US ICUs with the adoption of restrictive strategy.

Methods

A model, utilizing inputs from published studies, was constructed. Step 1 calculated potential number of patients appropriate for this strategy. In step 2, total number of pRBC units avoided with the restrictive trigger was extrapolated to the annual TFs in the US ICUs. Step 3 quantified excess acute complications and the number of pRBC units TF/1 TSAC in the TRICC trial. Step 4 transformed restrictive strategy-related avoidance of pRBC units to a reduction in TSACs, and step 5 quantified the associated cost savings.

Results

Of the 4.4 million annual ICU admissions, 1,020,800 comprised the at-risk population. The total of 1,295,126 units of pRBC ($643/unit) could be saved with the restrictive strategy. Based on the data from the TRICC trial, dividing the 49 excess complications in the liberal group into the calculated excess of pRBCs transfused (1,624 units) yielded the rate of 33 pRBC units per one complication. Thus, dividing 1,295,126 units saved by 33 units/1 TSAC, the base-case analysis showed that 39,246 TSACs could potentially be avoided annually in the US ICUs, with the cost savings of $821,109,826.

Conclusion

This model demonstrates that a restrictive transfusion strategy in appropriate at risk ICU patients is dominant and could result in improved quality of care and cost savings. Given the potential savings of 40,000 TSACs and nearly $1 billion, it is incumbent upon the intensivist community to promote more ubiquitous adoption of a clinically appropriate restrictive transfusion strategy in the ICU.
Design of an improved set of oligonucleotide primers for genotyping MeCP2tm1.1BirdKO mice by PCR
Authors: Miralvès Julie , Magdeleine Eddy , Joly Etienne
Published: August 2007

Background

The strain of MeCP2tm1.1Bird mice is a broadly used model for Rett syndrome. Because males carrying the invalidated MeCP2 locus are sterile, this strain has to be maintained in a heterozygous state. All animals therefore have to be genotyped at every generation to discriminate those carrying the invalidated allele (+/- females and y/- males) from those that do not. This is conveniently carried out by PCR on tail genomic DNA but because the primer pairs described initially for this purpose yield very similar size DNA bands on the WT and the KO alleles, this requires to carry out two independent PCR reactions on tail DNA preparations from all animals.

Results

After cloning and sequencing the PCR fragment amplified on the KO allele, we tested several sets of primers that were designed to yield PCR fragments of different sizes on the KO and WT alleles.

Conclusion

We have thus identified a set of three primers that allows for efficient genotyping of the animals by a single PCR reaction. Furthermore, using of this set of primers also resolves a recurrent problem related to the tendency of one of the initial primers to give rise to a non specific band because of its capacity to anneal at both ends of a repeated genomic element which we have identified as MurvyLTR.
Modeling gene expression regulatory networks with the sparse vector autoregressive model
Authors: Fujita André , Sato João R , Garay-Malpartida Humberto M , Yamaguchi Rui , Miyano Satoru , Sogayar Mari C , Ferreira Carlos E
Published: August 2007

Background

To understand the molecular mechanisms underlying important biological processes, a detailed description of the gene products networks involved is required. In order to define and understand such molecular networks, some statistical methods are proposed in the literature to estimate gene regulatory networks from time-series microarray data. However, several problems still need to be overcome. Firstly, information flow need to be inferred, in addition to the correlation between genes. Secondly, we usually try to identify large networks from a large number of genes (parameters) originating from a smaller number of microarray experiments (samples). Due to this situation, which is rather frequent in Bioinformatics, it is difficult to perform statistical tests using methods that model large gene-gene networks. In addition, most of the models are based on dimension reduction using clustering techniques, therefore, the resulting network is not a gene-gene network but a module-module network. Here, we present the Sparse Vector Autoregressive model as a solution to these problems.

Results

We have applied the Sparse Vector Autoregressive model to estimate gene regulatory networks based on gene expression profiles obtained from time-series microarray experiments. Through extensive simulations, by applying the SVAR method to artificial regulatory networks, we show that SVAR can infer true positive edges even under conditions in which the number of samples is smaller than the number of genes. Moreover, it is possible to control for false positives, a significant advantage when compared to other methods described in the literature, which are based on ranks or score functions. By applying SVAR to actual HeLa cell cycle gene expression data, we were able to identify well known transcription factor targets.

Conclusion

The proposed SVAR method is able to model gene regulatory networks in frequent situations in which the number of samples is lower than the number of genes, making it possible to naturally infer partial Granger causalities without anya prioriinformation. In addition, we present a statistical test to control the false discovery rate, which was not previously possible using other gene regulatory network models.
Reduced number and impaired function of circulating progenitor cells in patients with systemic lupus erythematosus
Authors: Moonen Jan Renier AJ , de Leeuw Karina , van Seijen Xavier J Gallego Y , Kallenberg Cees GM , van Luyn Marja JA , Bijl Marc , Harmsen Martin C
Published: August 2007

Systemic lupus erythematosus (SLE) is associated with premature and accelerated atherosclerosis. Circulating progenitor cells (CPCs) are circulating bone-marrow derived cells that play an important role in the repair of vascular damage that underlies the development of atherosclerosis. The objective of this study was to determine the number and functionality of CPCs in patients with SLE. The study included 44 female SLE patients in an inactive stage of disease and 35 age-matched female controls. CPC numbers in the circulation were determined by FACS with monoclonals against CD14, CD34 and CD133. Peripheral blood-derived mononuclear cell (PBMNC) fractions were cultured in angiogenic medium. The endothelial-like phenotype was confirmed and the colony forming unit (CFU) capacity, migratory capacity and the potential to form clusters on Matrigel were determined. Expression of apoptosis inhibiting caspase 8L was analyzed in PBMNCs and CPCs by gene transcript and protein expression assays. The number of CD34–CD133 double-positive cells (P < 0.001) as well as the CFU capacity (P = 0.048) was reduced in SLE patients. Migratory activity on tumor necrosis factor-α tended to be reduced in patient CPCs (P = 0.08). Migration on vascular endothelial growth factor showed no significant differences, nor were differences observed in the potential to form clusters on Matrigel. The expression of caspase 8L was reduced at the transcriptional level (P = 0.049) and strongly increased at the protein level after culture (P = 0.003). We conclude that CPC numbers are reduced in SLE patients and functionality is partly impaired. We suggest these findings reflect increased susceptibility to apoptosis of CPCs from SLE patients.
1,1-Bis(3'-indolyl)-1-(p-biphenyl)methane inhibits basal-like breast cancer growth in athymic nude mice
Authors: Su Yunpeng , Vanderlaag Kathryn , Ireland Courtney , Ortiz Janelle , Grage Henry , Safe Stephen , Frankel Arthur E
Published: August 2007

Introduction

1,1-Bis (3'-indolyl)-1-(p-biphenyl) methane (CDIM9) has been identified as a new peroxisome proliferator-activated receptor (PPAR)-γ agonist that exhibits both receptor dependent and independent antitumor activities. CDIM9 has not previously been studied with respect to its effects against basal-like breast cancer. Our goal in the present study was to investigate the anti-basal-like breast tumor activity of CDIM9 in vitro and in vivo.

Methods

The effects of CDIM9 on cell protein and DNA syntheses were determined in basal-like breast cancer MDA-MB231 and BT549 cells in vitro. Maximum tolerated dose and dose-limited toxicity were determined in BalB/c mice, and antitumor growth activities were assessed in MDA-MB231 basal-like breast tumor xenografts in athymic nude mice.

Results

CDIM9 exhibited selective cell cytotoxicity and anti-proliferation effects on basal-like breast cancer lines. In MDA-MB231 cell, CDIM9 induced caveolin-1 and p27 expression, which was significantly downregulated by co-treatment with the PPAR-γ antagonist GW9662. Nonsteroidal anti-inflammatory drug-activated gene-1 and activating transcription factor-3 were upregulated by CDIM9 through a PPAR-γ independent pathway. CDIM9 (40 mg/kg daily, intraperitoneally, for 35 days) inhibited the growth of subcutaneous MDA-MB231 tumor xenografts by 87%, and produced a corresponding decrease in proliferation index. Nearly half of the treated mice (46%) had complete durable remissions, confirmed by histology. The growth of an established tumor was inhibited by CDIM9 treatment (64 mg/kg daily, intraperitoneally, for 10 days), with a mean tumor growth inhibition of 67% as compared with controls. CDIM9 induced increases in tumor caveolin-1 and p27 in vivo, which may contribute to its antitumor activity in basal-like breast cancer.

Conclusion

CDIM9 showed potent antiproliferative effects on basal-like breast cancer cell in tissue culture and dramatic growth inhibition in animal models at safe doses. These findings justify further development of this drug for treatment of basal-like breast cancer.
Placental growth factor down-regulates type 1 T helper immune response by modulating the function of dendritic cells
Authors: Lin Yu-Li , Liang Yu-Chih , Chiang Bor-Luen
Published: August 2007

Placental growth factor (PlGF) belongs to the vascular endothelial growth factor (VEGF) family and represents a key regulator of angiogenic events in development and pathologic conditions. In this study, PlGF-modulated differentiation and maturation of human dendritic cells (DCs) from CD14+ monocytes were investigated. The DC, differentiated from CD14+ monocytes in the presence of PlGF during 5 days, was referred to as “PlGF-DC”, in contrast to the “classical-DC”, obtained in the absence of PlGF. Treatment of PlGF-DC or classical-DC with PlGF resulted in the down-regulation of CD80, CD86, CD83, CD40, and HLA-DR expression, and CD1a was increased, as well as the inhibition of IL-12 p70, p40, IL-8, and TNF-α production in response to LPS stimulation. This PlGF-induced DC dysfunction was recovered by anti-human VEGF receptor 1 mAb. In addition, treatment of PlGF-DC or classical-DC with PlGF resulted in the suppression of naïve CD4+ T cell proliferation in an allogenic MLR but up-regulated the IL-5 and IL-13 secretion of the CD4+ T cell. PlGF was also able to inhibit LPS-induced IκBα phosphorylation and NF-κB activity. Taken together, our data demonstrate that the immunosuppressive properties of PlGF are through the NF-κB signaling pathway. PlGF might play a major role in the pathogenesis of tumors and act as an effector molecule to skew T cell response to the Th2 phenotype, which might be more beneficial for pregnancy.
Inhibitory receptor gp49B regulates eosinophil infiltration during allergic inflammation
Authors: Norris Hillary H , Peterson Mary E , Stebbins Chris C , McConchie Brittany W , Bundoc Virgilio G , Trivedi Shweta , Hodges Marcus G , Anthony Robert M , Urban Joseph F , Long Eric O , Keane-Myers Andrea M
Published: August 2007

gp49B, an Ig-like receptor, negatively regulates the activity of mast cells and neutrophils through cytoplasmic immunoreceptor tyrosine-based inhibition motifs. To characterize the role of gp49B further in vivo, gp49B-deficient mice were tested in two allergic models. Responses to ragweed (RW) challenge in the lung and conjunctiva were assessed in models of allergic inflammation and during an infection with parasitic larvae of the nematode Ascaris suum. Infiltration by inflammatory cells into the lung during allergic responses was under negative control of the inhibitory receptor gp49B. Furthermore, an increase in conjunctival inflammation with a predominance of eosinophils, neutrophils, and degranulated mast cells was observed in RW-sensitized, gp49B-deficient mice, which had been challenged in the eye, as compared with C57BL/6 wild-type (WT) controls. Finally, an increase in allergic inflammation in the lungs of A. suum-infected, RW-sensitized mice was observed upon RW challenge, as compared with C57BL/6 WT controls. The observed influx of eosinophils into mucus membranes is characteristic of allergic asthma and allergic conjunctivitis and may contribute to airway hyper-responsiveness, airway remodeling, and mucus production. Expression of gp49B was detected on peripheral eosinophils of control mice and on eosinophils from lungs of mice treated with RW, suggesting a role for gp49B on eosinophils in dampening allergic inflammatory responses.
Measuring grammatical complexity: the Gordian knot
Authors: Rimmer Wayne
Published: August 2007

Grammar is central to language description and a posteriori construct validation of language tests consistently identifies grammar as a significant factor in differentiating between score levels and characterizing overall proficiency. However, there is currently no model of grammatical competence robust enough to be operationalized in tests. Critical to describing grammatical competence is complexity of form and structure, yet grammatical complexity is poorly defined in linguistics and its sub-disciplines, including language assessment. This article argues that the inherent subjectiveness of complexity can be much reduced by a research methodology that combines input from corpora with expert intuition of the linguistic status of the grammatical items retrieved. The significance of the discussion is that, in addition to contributing to the on-going process of construct validity, a corpus-informed study of complexity has the potential to reconcile the tension in theoretical linguistics between grammar as being sentence-bound and grammar as discourse.
On the use of the immediate recall task as a measure of second language reading comprehension
Authors: Chang Yuh-Fang
Published: August 2007

The immediate written recall task, a widely used measure of both first language (L1) and second language (L2) reading comprehension, has been advocated over traditional test methods such as multiple choice, cloze tests and open-ended questions because it is a direct and integrative assessment task. It has been, however, criticized as requiring memory. Whether and how the requirement of memory biases our understanding of readers’ comprehension remains unexplored. This study compares readers’ performance on the immediate recall and a translation task in order to explore the effect of memory on readers’ recall. Ninety-seven college students participated in this study. All participants were native speakers of Mandarin Chinese whose ages ranged from 20 to 22. The results showed that the translation task yielded significantly more evidence of comprehension than did the immediate recall task, which indicates that the requirement of memory in the recall task hinders test-takers’ ability to demonstrate fully their comprehension of the reading passage. The results also showed that the significant difference found in learners’ performance between the immediate recall and the translation task spanned the effect of topics and proficiency levels.
Periodic Markov switching autoregressive models for Bayesian analysis and forecasting of air pollution
Authors: Spezia Luigi , Paroli Roberta , Dellaportas Petros
Published: August 2007

Markov switching autoregressive models (MSARMs) are efficient tools to analyse nonlinear and non-Gaussian time series. A special MSARM with two harmonic components is proposed to analyse periodic time series. We present a full Bayesian analysis based on a Gibbs sampling algorithm for model choice and the estimations of the unknown parameters, missing data and predictive distributions. The implementation and modelling steps are developed by tackling the problem of the hidden states labeling by means of random permutation sampling and constrained permutation sampling. We apply MSARMs to study a data set about air pollution that presents periodicities since the hourly mean concentration of carbon monoxide varies according to the dynamics of the 24 day-hours and of the year. Hence, we introduce in the model both a hidden state-dependent daily component and a state-independent yearly component, giving rise to periodic MSARMs.
An empirical model for underdispersed count data
Authors: Ridout Martin S , Besbeas Panagiotis
Published: August 2007

We present a novel distribution for modelling count data that are underdispersed relative to the Poisson distribution. The distribution is a form of weighted Poisson distribution and is shown to have advantages over other weighted Poisson distributions that have been proposed to model underdispersion. One key difference is that the weights in our distribution are centred on the mean of the underlying Poisson distribution. Several illustrative examples are presented that illustrate the consistently good performance of the distribution.
Bayesian inference for stochastic epidemics in closed populations
Authors: Streftaris George , Gibson Gavin J
Published: August 2007

We consider continuous-time stochastic compartmental models that can be applied in veterinary epidemiology to model the within-herd dynamics of infectious diseases. We focus on an extension of Markovian epidemic models, allowing the infectious period of an individual to follow a Weibull distribution, resulting in a more flexible model for many diseases. Following a Bayesian approach we show how approximation methods can be applied to design efficient MCMC algorithms with favourable mixing properties for fitting non-Markovian models to partial observations of epidemic processes. The methodology is used to analyse real data concerning a smallpox outbreak in a human population, and a simulation study is conducted to assess the effects of the frequency and accuracy of diagnostic tests on the information yielded on the epidemic process.
Developmental aspects of schizophrenia and related disorders: possible implications for treatment strategies
Authors: Davies Eric J.
Published: August 2007

Schizophrenia and other schizophrenia-spectrum disorders are neurodevelopmental disorders which may share genetic susceptibility factors and represent differential expressions of an underlying vulnerability. Schizophrenia may have its onset in childhood and can be reliably diagnosed. However, developmental factors modulate disease expression in children. Although the prevalence of schizophrenia in childhood is low, children who develop schizophrenia in adult life may show subtle and non-specific developmental abnormalities, consistent with the neurodevelopmental hypothesis. Studies of the schizophrenia prodrome also demonstrate that abnormalities may be apparent years before the onset of positive symptoms. Such evidence raises the possibility of using preventive approaches in the treatment of schizophrenia. Further advances in our knowledge of the aetiopathology of schizophrenia (and the identification of endophenotypes within the group of schizophrenia and related disorders) may further improve our ability to predict disease development, making implementation of preventive interventions more achievable.
Ethnic bias in the application of the Mental Health Act 1983
Authors: Dein Kalpana , Williams Paul Simon , Dein Simon
Published: August 2007

There is evidence pointing to a bias in the application of the Mental Health Act 1983 (which is in force in England and Wales). One study found that Black people on in-patient units were four times more likely to have been compulsorily admitted than White people. Furthermore, it has been shown that compulsory admissions to secure units are 2.9–5.6 times higher for Black than for White patients. Any understanding of this bias necessitates an examination of the attitudes of mental health professionals towards Africans and African–Caribbeans. Here we discuss possible contributory factors and examine a number of initiatives that have been instituted in order to tackle this problem.
Intimate partner violence: treating abuser and abused
Authors: Heru Alison M.
Published: August 2007

Intimate partner violence is associated with significant psychiatric comorbidity. Treatment has focused on male perpetrators but recent studies indicate that this is of limited success in reducing male violence. This article reviews the current available treatments from three perspectives: that of the victim, the perpetrator, and the couple who wish to remain together. It also provides guidelines to assist the general psychiatrist in determining what treatment to offer patients who present with intimate partner violence. Guidelines emphasise the need for assessment of risk factors that indicate a potentially lethal relationship and the importance of the diagnosis and treatment of comorbidity, especially alcohol misuse and dependence.
Insight in psychosis: influence of cognitive ability and self-esteem
Authors: Cooke Michael A. , Peters Emmanuelle R. , Greenwood Kathryn E. , Fisher Peter L. , Kumari Veena , Kuipers Elizabeth
Published: August 2007

Background

Insight in psychosis has previously been associated with both depression and cognitive ability. Some studies have found a curvilinear relationship between insight and cognitive ability but the roles of self-esteem and depression have not been taken into account.

Aims

To investigate the relationships between insight and IQ, depression, and self-esteem.

Method

Correlations between self-reported and observer-rated insight, and measures of IQ, depression and self-esteem were examined in 67 people with psychosis.

Results

Better self-reported insight was associated with higher IQ and poorer self-esteem, but not depression. There was some evidence for a curvilinear relationship between IQ and self-reported insight, specifically the ‘awareness of illness' dimension, which survived correction for symptom variables.

Conclusions

The relationship between insight and IQ might reflect both the basis of insight in intellectual ability and the influence of a psychological mechanism that preserves self-esteem.
Antipsychotic treatment of primary delusional parasitosis
Authors: Lepping Peter , Russell Ian , Freudenmann Roland W
Published: August 2007

Background

Little is known about the treatment of delusional parasitosis with typical and atypical antipsychotics.

Aims

To evaluate the effectiveness of typical and atypical antipsychotics in primary delusional parasitosis (delusional disorder, somatic type).

Method

A systematic review was conducted.

Results

No randomised trials were found and hence we collected the best evidence from 16 other trials and case reports, separating primary from other forms of delusional parasitosis. Studies using typical antipsychotics showed partial or full remission in between 60 and 100% of patients. Analysis of selected patients with primary delusional parasitosis showed that typical and atypical antipsychotics were effective in the majority, but that remission rates did not differ significantly between typical and atypical antipsychotics.

Conclusions

In the absence of controlled trials there is limited evidence that antipsychotics are effective in primary delusional parasitosis. Rigorous studies are needed to evaluate their effectiveness and to compare typical and atypical antipsychotics directly.
Guided self-help in primary care mental health
Authors: Khan Nagina , Bower Peter , Rogers Anne
Published: August 2007

Background

There is a gap between the supply of trained cognitive – behavioural therapists to treat depression and demand for care in the community. There is interest in the potential of self-help interventions, which require less input from a therapist. However, the design of effective self-help interventions is complex. Qualitative research can help to explore some of this complexity Aims The study aimed to identify qualitative studies of patient experience of depression management in primary care, synthesise these studies to develop an explanatory framework, and then apply this framework to the development of a guided self-help intervention for depression.

Method

A meta-synthesis was conducted of published qualitative research.

Results

The synthesis revealed a number of themes, including the nature of personal experience in depression; help-seeking in primary care; control and helplessness in engagement with treatment; stigma associated with treatment; and patients' understandings of self-help interventions.

Conclusions

This meta-synthesis of qualitative studies provided a useful explanatory framework for the development of effective and acceptable guided self-help interventions for depression.
Genetic risk of depression and stress-induced negative affect in daily life
Authors: Wichers Marieke , Myin-Germeys Inez , Jacobs Nele , Peeters Frenk , Kenis Gunter , Derom Catherine , Vlietinck Robert , Delespaul Philippe , Van Os Jim
Published: August 2007

Background

A bias to develop negative affect in response to daily life stressors may be an important depression endophenotype, but remains difficult to assess.

Aims

To assess this mood bias endophenotype, uncontaminated by current mood, in the course of daily life.

Method

The experience samping method was used to collect multiple appraisals of daily life event-related stress and negative affect in 279 female twin pairs. Cross-twin, cross-trait associations between daily life mood bias and DSM – IV depression were conducted.

Results

Probands whose co-twins were diagnosed with lifetime depression showed a stronger mood bias to stress than those with co-twins without such a diagnosis, independent of probands' current depressive symptoms and to a greater extent in monozygotic twins than in dizygotic twins.

Conclusions

Genetic liability to depression is in part expressed as the tendency to display negative affect in response to minor stressors in daily life. This trait may represent a true depression endophenotype.
Firearm legislation reform in the European Union: impact on firearm availability, firearm suicide and homicide rates in Austria
Authors: Kapusta Nestor D. , Etzersdorfer Elmar , Krall Christoph , Sonneck Gernot
Published: August 2007

Background

The availability of firearms in homes and at aggregate levels is a risk factor for suicide and homicide. One method of reducing access to suicidal means is the restriction of firearm availability through more stringent legislation.

Aims

To evaluate the impact of firearm legislation reform on firearm suicides and homicides as well as on the availability of firearms in Austria.

Method

Official statistics on suicides, firearm homicides and firearm licences issued from 1985 to 2005 were examined. To assess the effect of the new firearm law, enacted in 1997, linear regression and Poisson regressions were performed using data from before and after the law reform.

Results

The rate of firearm suicides among some age groups, percentage of firearm suicides, as well as the rate of firearm homicides and the rate of firearm licences, significantly decreased after a more stringent firearm law had been implemented.

Conclusions

Our findings provide evidence that the introduction of restrictive firearm legislation effectively reduced the rates of firearm suicide and homicide. The decline in firearm-related deaths seems to have been mediated by the legal restriction of firearm availability. Restrictive firearm legislation should be an integral part of national suicide prevention programmes in countries with high firearm suicide rates.
Familial liability to schizophrenia and premorbid adjustment
Authors: Walshe Muriel , Taylor Mark , Schulze Katja , Bramon Elvira , Frangou Sophia , Stahl Daniel , Kravariti Eugenia , Daly Eileen , Fearon Paul , Murray Robin M. , Mcdonald Colm
Published: August 2007

We assessed premorbid functioning during childhood and adolescence in 50 people with schizophrenia from multiply affected families, 39 of their unaffected siblings, 69 people with schizophrenia with no family history of psychosis, 67 of their unaffected siblings and 83 controls. People with schizophrenia had poorer premorbid social and academic adjustment and exhibited a decline between childhood and adolescence compared with controls. Unaffected siblings from multiply affected families also had poor academic functioning in adolescence, with a decline between childhood and adolescence. This may represent a familial (presumed genetic) effect.
Management of insomnia: treatments and mechanisms
Authors: Wilson Sue , Nutt David
Published: August 2007

Management of insomnia is an interesting subject at present. New drug treatments are now becoming available after a relatively static period since the development of the Z-drugs in the 1990s. Moreover, more evidence is coming to light about the length of drug treatment and the effectiveness of psychological therapies. This article briefly describes current treatments, both evidence-based and common practice, and goes on to describe some emerging approaches.
What is the heartland of psychiatry?
Authors: Goodwin Guy M. , Geddes John R.
Published: August 2007

Psychiatry has long identified schizophrenia as its defining disorder, its heartland as it has been called. In the past 20 years, this has had a number of negative consequences for psychiatry as a medical specialty, which result from the uncertainty of diagnosis and an increasing emphasis on demedicalising services in an attempt to provide social care outside hospital. These changes have probably increased the stigma attached to psychiatric practice and threaten to deskill doctors. They have also meant that services for other disorders do not meet the needs of patients. To continue to allow schizophrenia to be the paradigm condition is against the interests of psychiatrists and their patients.