bluuebunny/crossref_metadata_2025 huggingface dataset:
Treatment Engagement With a Sexual Offender Who Denies Committing the Offense
Authors: Ware Jayson , Marshall W.L.
Published: June 2008

This case study describes a strategy for treating a sexual offender who categorically denies committing the offense. These offenders usually refuse to participate in treatment or are deemed ineligible or unsuitable for sexual offender treatment on the basis of their denial of responsibility. The treatment approach outlined in this case study reflects an adaptation of conventional sexual offender treatment such that the focus is on the problems in the offender's life that led to him or her to be in a position where he or she could be “accused” of an offense. This case study demonstrates how an offender who is categorically denying responsibility for his offending was therapeutically engaged in treatment. Treatment implications of this approach are discussed.
Social and Environmental Contexts of Adolescent and Young Adult Male Perpetrators of Intimate Partner Violence: A Qualitative Study
Authors: Reed Elizabeth , Silverman Jay G. , Raj Anita , Rothman Emily F. , Decker Michele R. , Gottlieb Barbara R. , Molnar Beth E. , Miller Elizabeth
Published: June 2008

The purpose of the current study was to examine qualitatively the life contexts of young males enrolled in programs addressing perpetration of intimate partner violence (IPV). Semistructured interviews were conducted with 19 males recruited from these programs. Interviews were coded to examine life contexts and analyzed using a content analysis approach. Five themes emerged across interviews: ( a) disruptive home environment; ( b) lack of positive male role models; ( c) a peer context characterized by substance use, gang involvement, and behaviors supporting the sexual maltreatment of girls; ( d) school circumstances characterized by a lack of academic support; and ( e) community exposures to violence. These factors were often interrelated within the various contexts of participants. Further research is needed to provide insight into whether and how these issues may contribute to IPV perpetration. Efforts to support young males regarding a broad array of concerns should be included in programming to reduce IPV perpetration.
The Reliability of Measurements Taken from Computer-Stored Digitalised X-Rays of Acute Distal Radius Fractures
Authors: THOMASON K. , SMITH K. L.
Published: June 2008

Sixteen observers measured eight anatomical parameters on digitalised images of six acute distal radial fractures using the Patient Archiving Communication System software and repeated the measurements at least 2 weeks later. Inter- and intraobserver reliability was calculated using intraclass correlation coefficients and tolerance limits. The highest interobserver agreement was demonstrated in the dorsal tilt (intraclass correlation coefficient 0.858; tolerance limit 14.2°). When compared with the results of a study looking at observer reliability in measurement of healed distal radial fractures, the reliability of computerised measurements is not significantly different from those achieved by manual techniques (dorsal tilt interobserver tolerance limits on computer system 16°, compared to 15° using ruler and protractor). These results suggest that the recommended radiological reduction limits for distal radius fractures of <10° change in palmar tilt, <2 mm radial shortening, <5° change in radial angle and a <1 to 2 mm articular step cannot be reliably measured.
Complex Articular Fractures of the Distal Radius: The Role of Closed Reduction and External Fixation
Authors: BINI A. , SURACE M. F. , PILATO G.
Published: June 2008

Twenty-two patients underwent surgery for 23 complex articular fractures of the distal radius of C.3 type, according to the AO classification. The surgical treatment consisted, in all cases, of a closed, or limited-open, reduction and external fixation. The functional and radiographic results were analysed at a mean follow-up of 40 months. This retrospective study confirms that satisfactory functional results where obtained in 12 out of the 15 wrists where all the intra and extra-articular parameters of the Fernandez’ criteria where respected. For those wrists where keeping with Fernandez’ criteria for intra-articular parameters and ulnar variance was not possible, four of eight had satisfactory results. As far as the acceptability criteria for radial inclination and dorsal tilt are concerned, the functional results seem to suggest that a little wider tolerance than proposed in the literature could be accepted.
Tolerance of Upper Extremity Pneumatic Tourniquets and their Effect on Grip Strength
Authors: PRODHOMME G. , MOURAUX D. , DUGAILLY P. -M. , CHANTELOT C. , FONTAINE C. , SCHUIND F.
Published: June 2008

This study was undertaken to evaluate tourniquet tolerance in healthy people. An arm tourniquet was inflated to 100 mmHg above systolic blood pressure for 21 minutes. We measured pain and grip strength before, during and at various times after deflation. We tested 40 subjects (20 women and 20 men) with an average age of 38 (range 22–58) years. Eight individuals did not tolerate the tourniquet for this length of time and the test was stopped. Visual analogical scale had a globally linear increase during tourniquet application. We noted a sensation of well-being just after deflation, quickly replaced by pain in the tested limb due to limb reperfusion. We also noted a significant loss of strength in the tested limb, which completely recovered by 48 hours. We also observed a significant loss of strength in the contralateral hand, which also recovered by 48 hours. The possible reasons for these temporary losses of strength in both the ipsilateral and contralateral limbs are discussed.
The Triad of Multiple Metacarpal Fractures and/or Dislocations of the Fingers, Severe Hand Swelling and Clinical Evidence of Acute Median Nerve Dysfunction
Authors: AL-QATTAN M. M.
Published: June 2008

Twenty-five cases of crush injury to the hand resulting in the triad of multiple finger metacarpal fractures/dislocations of the fingers, a balloon hand appearance due to severe swelling and clinical evidence of acute median nerve dysfunction were retrospectively reviewed. All were men with a mean age of 33 (range 20–45) years. All injuries occurred following industrial or major car accidents. The fracture site included metacarpal head/neck fractures, metacarpal shaft fractures and carpometacarpal joint fracture–dislocations. All patients underwent fasciotomies, open carpal tunnel release and fixation of displaced fractures, followed by immediate mobilisation of the fingers. At a mean final follow-up of 7 (range 6–8) months, full recovery of median nerve function was seen in all patients. The final mean total active motion of the fingers was 243°, 230° and 250° in displaced distal, middle and proximal impact fractures, respectively. All patients were able to return back to work.
Hand Strengths in Carpal Tunnel Syndrome
Authors: KAYMAK B. , İNANICI F. , ÖZÇAKAR L. , ÇETIN A. , AKINCI A. , HASÇELIK Z.
Published: June 2008

The purpose of this study was to determine whether a measurable decrease in isokinetic (dynamic) and isometric (static) hand strengths occurs in carpal tunnel syndrome (CTS) patients. Eighteen CTS patients and 20 healthy controls were included in the study. Isokinetic (eccentric and concentric) and isometric grip and pinch strengths were measured with a Biodex System 3 dynamometer (Biodex Medical System, Inc. New York). All strength measurements, except isometric and isokinetic (concentric/eccentric) three-point pinch and isokinetic (concentric) tip pinch, revealed statistically significant differences between CTS patients and controls. Measurable decrease in hand strengths may exist in CTS despite normal manual assessments. Although both isokinetic (dynamic) and isometric (static) dynamometers are capable of detecting this decrease, neither technique seems better than the other.
Fibrinolytic Treatment of Acute Arterial Occlusion Distal to the Wrist in two Cases
Authors: WITZ M. , SAGIV P. , LEHMANN J. M.
Published: June 2008

Distal arterial occlusion in the hand threatens the viability of the digits and is difficult to treat. This study reports two cases in which fibrinolytic agents were used successfully to restore circulation in the digital arteries.
Bone Morphogenetic Protein as an Adjuvant in the Treatment of Kienbock’s Disease by Vascular Pedicle Implantation
Authors: JONES N. F. , BROWN E. E. , VÖGELIN E. , URIST M. R.
Published: June 2008

This case report documents the first use of bone morphogenetic protein (BMP) as an adjuvant to revascularisation with a first dorsal metacarpal arterio-venous pedicle in the treatment of a patient with Stage III Kienbock’s disease. The patient had complete relief of her symptoms of wrist pain by 8 months postoperatively, when X-rays showed no further evidence of lunate collapse and an MRI scan demonstrated islands of revascularisation. It is impossible to prove unequivocably that BMP contributed to the result seen in this one patient, but this adjuvant concept is based on experimental evidence demonstrating that optimal bioengineering of vascularised bone is dependent on four factors – a structural matrix, progenitor cells, BMP and a vascular supply, and BMP may play a future role in promoting new bone formation in Kienbock’s disease.
(+)-Catechin inhibits tumour angiogenesis and regulates the production of nitric oxide and TNF-α in LPS-stimulated macrophages
Authors: Guruvayoorappan Chandrasekharan , Kuttan Girija
Published: June 2008

The anti-angiogenic activity of (+)-catechin as well as its regulatory effect on the production of nitric oxide and TNFα were studied using in vivo and in vitro models. In vivo angiogenic activity was studied using B16F-10 melanoma cell-induced capillary formation in C57BL/6 mice. Administration of (+)-catechin significantly inhibited (36.09%) the number of tumour-directed capillaries induced by injecting B16F-10 melanoma cells on the ventral side of C57BL/6 mice. The cytokine profile in the serum of these animals showed a drastically increased level of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, GM-CSF and the direct endothelial cell proliferating agent, VEGF. Administration of (+)-catechin could differentially regulate elevation of these cytokines. The differential elevation is further evidenced by the increased production of IL-2 and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the B16F-10 injected, (+)-catechin-treated animals. In vitro L929 bioassay revealed the inhibition of TNF-α production by (+)-catechin treatment. In the rat aortic ring assay, (+)-catechin inhibited the microvessel outgrowth at non-toxic concentrations. (+)-Catechin at non-toxic concentrations (5—25 µg/ml) showed significant inhibition in the proliferation, migration and tube formation of endothelial cells, which are the key events in the process of angiogenesis. (+)-Catechin also showed inhibitory effect on VEGF mRNA levels in B16F-10 melanoma cells. (+)-Catechin inhibited the production of NO and TNF-α in LPS-stimulated primary macrophages. Taken together, these results demonstrate that (+)-catechin inhibits tumour-specific angiogenesis by regulating the production of pro- and anti-angiogenic factors such as pro-inflammatory cytokines, nitric oxide, VEGF, IL-2 and TIMP-1. These results also suggest that (+)-catechin could significantly inhibit nitrite and TNF-α production in LPS-stimulated macrophages.
Chronic graft-versus-host disease following umbilical cord blood transplantation: retrospective survey involving 1072 patients in Japan
Authors: Narimatsu Hiroto , Miyakoshi Shigesaburo , Yamaguchi Takuhiro , Kami Masahiro , Matsumura Tomoko , Yuji Koichiro , Murashige Naoko , Kusumi Eiji , Kodama Yuko , Komatsu Tsunehiko , Sakamaki Hisashi , Kouzai Yasushi , Okada Masaya , Osugi Yuko , Kobayashi Ryoji , Inoue Masami , Takahashi Satoshi , Kai Shunro , Kato Koji , Inoue-Nagamura Tokiko , Taniguchi Shuichi , Kato Shunichi
Published: June 2008

We have little information on chronic graft-versus-host disease (GVHD) after cord blood transplantation (CBT). We investigated its clinical features in 1072 Japanese patients with hematologic malignancies who received a transplant through the Japan Cord Blood Bank Network. The primary end point was to investigate the incidence of any chronic GVHD. Median age of the patients was 33 years (range, 0-79 years). The cumulative incidence of chronic GVHD 2 years after transplantation was 28%. Chronic GVHD was fatal in 29 patients. Multivariate analysis demonstrated that development of chronic GVHD was favorably associated with both overall survival and event-free survival. Multivariate analysis identified risk factors of chronic GVHD: higher patient body weight, higher number of mismatched antigens for GVHD direction, myeloablative preparative regimen, use of mycophenolate mofetil in GVHD prophylaxis, and development of grades II to IV acute GVHD. Although chronic GVHD is a significant problem after CBT, it is associated with improved survival, perhaps due to graft-versus-malignancy effects.
Macrophages contribute to the cellular uptake of von Willebrand factor and factor VIII in vivo
Authors: van Schooten Carina J. , Shahbazi Shirin , Groot Evelyn , Oortwijn Beatrijs D. , van den Berg H. Marijke , Denis Cécile V. , Lenting Peter J.
Published: June 2008

Von Willebrand factor (VWF) and factor VIII (FVIII) circulate in a tight noncovalent complex. At present, the cells that contribute to the removal of FVIII and VWF are of unknown identity. Here, we analyzed spleen and liver tissue sections of VWF-deficient mice infused with recombinant VWF or recombinant FVIII. This analysis revealed that both proteins were targeted to cells of macrophage origin. When applied as a complex, both proteins were codirected to the same macrophages. Chemical inactivation of macrophages using gadolinium chloride resulted in doubling of endogenous FVIII levels in VWF-null mice, and of VWF levels in wild-type mice. Moreover, the survival of infused VWF was prolonged almost 2-fold in VWF-deficient mice after gadolinium chloride treatment. VWF and FVIII also bound to primary human macrophages in in vitro tests. In addition, radiolabeled VWF bound to human THP1 macrophages in a dose-dependent, specific, and saturable manner (half-maximal binding at 0.014 mg/mL). Binding to macrophages was followed by a rapid uptake and subsequent degradation of the internalized protein. This process was also visualized using a VWF–green fluorescent protein fusion protein. In conclusion, our data strongly indicate that macrophages play a prominent role in the clearance of the VWF/FVIII complex.
Detection of T lymphocytes with a second-site mutation in skin lesions of atypical X-linked severe combined immunodeficiency mimicking Omenn syndrome
Authors: Wada Taizo , Yasui Masahiro , Toma Tomoko , Nakayama Yuko , Nishida Mika , Shimizu Masaki , Okajima Michiko , Kasahara Yoshihito , Koizumi Shoichi , Inoue Masami , Kawa Keisei , Yachie Akihiro
Published: June 2008

X-linked severe combined immunodeficiency (XSCID) is caused by mutations of the common gamma chain (γc) and usually characterized by the absence of T and natural killer (NK) cells. Here, we report an atypical case of XSCID presenting with autologous T and NK cells and Omenn syndrome-like manifestations. The patient carried a splice-site mutation (IVS1+5G>A) that caused most of the mRNA to be incorrectly spliced but produced normally spliced transcript in lesser amount, leading to residual γc expression and development of T and NK cells. The skin biopsy specimen showed massive infiltration of revertant T cells. Those T cells were found to have a second-site mutation and result in complete restoration of correct splicing. These findings suggest that the clinical spectrum of XSCID is quite broad and includes atypical cases mimicking Omenn syndrome, and highlight the importance of revertant mosaicism as a possible cause for variable phenotypic expression.
Analysis of the spatial and temporal characteristics of platelet-delivered factor VIII–based clots
Authors: Neyman Michael , Gewirtz Jamie , Poncz Mortimer
Published: June 2008

Normally factor (F) VIII is not expressed in megakaryocytes, but when human FVIII was transgenically expressed in murine megakaryocytes, it was stored in platelet α-granules and released at sites of injury. This platelet FVIII (pFVIII) is effective in correcting hemostasis, even in the presence of circulating inhibitors, so it offers a potential gene therapy strategy for hemophilia A. To understand clot development by pFVIII, we have examined clot response to laser injury in both cremaster arterioles and venules in FVIIInull mice either infused with FVIII or transgenic for pFVIII. In both sets of vessels, pFVIII is at least as effective as infused FVIII. However, there are temporal and spatial differences in fibrin and platelet accumulation within clots depending on how FVIII is delivered. These differences may be related to the temporal and spatial distribution of the α-granular–released FVIII within the developing clot, and may explain the increased frequency and size of embolic events seen with pFVIII. These observations may not only have implications for the use of pFVIII in gene therapy for hemophilia A, but may also have physiologic consequences, explaining why many procoagulant factors are delivered both in the plasma and in platelet α-granules.
The combination approach of SVM and ECOC for powerful identification and classification of transcription factor
Authors: Zheng Guangyong , Qian Ziliang , Yang Qing , Wei Chaochun , Xie Lu , Zhu Yangyong , Li Yixue
Published: June 2008

Background

Transcription factors (TFs) are core functional proteins which play important roles in gene expression control, and they are key factors for gene regulation network construction. Traditionally, they were identified and classified through experimental approaches. In order to save time and reduce costs, many computational methods have been developed to identify TFs from new proteins and to classify the resulted TFs. Though these methods have facilitated screening of TFs to some extent, low accuracy is still a common problem. With the fast growing number of new proteins, more precise algorithms for identifying TFs from new proteins and classifying the consequent TFs are in a high demand.

Results

The support vector machine (SVM) algorithm was utilized to construct an automatic detector for TF identification, where protein domains and functional sites were employed as feature vectors. Error-correcting output coding (ECOC) algorithm, which was originated from information and communication engineering fields, was introduced to combine with support vector machine (SVM) methodology for TF classification. The overall success rates of identification and classification achieved 88.22% and 97.83% respectively. Finally, a web site was constructed to let users access our tools (see Availability and requirements section for URL).

Conclusion

The SVM method was a valid and stable means for TFs identification with protein domains and functional sites as feature vectors. Error-correcting output coding (ECOC) algorithm is a powerful method for multi-class classification problem. When combined with SVM method, it can remarkably increase the accuracy of TF classification using protein domains and functional sites as feature vectors. In addition, our work implied that ECOC algorithm may succeed in a broad range of applications in biological data mining.
Improving the prediction accuracy in classification using the combined data sets by ranks of gene expressions
Authors: Kim Ki-Yeol , Ki Dong Hyuk , Jeung Hei-Cheul , Chung Hyun Cheol , Rha Sun Young
Published: June 2008

Background

The information from different data sets experimented under different conditions may be inconsistent even though they are performed with the same research objectives. More than that, even when the data sets were generated from the same platform, the data agreement may be affected by the technical variation among the laboratories. In this case, it is necessary to use the combined data set after adjusting the differences between such data sets, for detecting the more reliable information.

Results

The proposed method combines data sets posterior to the discretization of data sets based on the ranks of the gene expression ratios, and the statistical method is applied to the combined data set for predictive gene selection. The efficiency of the proposed method was evaluated using five colon cancer related data sets, which were experimented using cDNA microarrays with different RNA sources, and one experiment utilized oligonucleotide arrays. NCI-60 cell lines data sets were used, which were performed with two different platforms of cDNA microarrays and Affymetrix HU6800 oligonucleotide arrays. The combined data set by the proposed method predicted the test data sets more accurately than the separated data sets did. The biological significant genes were detected from the combined data set, which were missed on the separated data sets.

Conclusion

By transforming gene expressions using ranks, the proposed method is not influenced by systematic bias among chips and normalization method. The method may be especially more useful to find predictive genes from data sets which have different scale in gene expressions.
Venezuelan equine encephalitis virus infection causes modulation of inflammatory and immune response genes in mouse brain
Authors: Sharma Anuj , Bhattacharya Bhaskar , Puri Raj K , Maheshwari Radha K
Published: June 2008

Background

Neurovirulent Venezuelan equine encephalitis virus (VEEV) causes lethal encephalitis in equines and is transmitted to humans by mosquitoes. VEEV is highly infectious when transmitted by aerosol and has been developed as a bio-warfare agent, making it an important pathogen to study from a military and civilian standpoint. Molecular mechanisms of VEE pathogenesis are poorly understood. To study these, the gene expression profile of VEEV infected mouse brains was investigated. Changes in gene expression were correlated with histological changes in the brain. In addition, a molecular framework of changes in gene expression associated with progression of the disease was studied.

Results

Our results demonstrate that genes related to important immune pathways such as antigen presentation, inflammation, apoptosis and response to virus (Cxcl10, CxCl11, Ccl5, Ifr7, Ifi27 Oas1b, Fcerg1,Mif, Clusterin and MHC class II) were upregulated as a result of virus infection. The number of over-expressed genes (>1.5-fold level) increased as the disease progressed (from 197, 296, 400, to 1086 at 24, 48, 72 and 96 hours post infection, respectively).

Conclusion

Identification of differentially expressed genes in brain will help in the understanding of VEEV-induced pathogenesis and selection of biomarkers for diagnosis and targeted therapy of VEEV-induced neurodegeneration.
Chloroplast DNA sequence of the green alga Oedogonium cardiacum (Chlorophyceae): Unique genome architecture, derived characters shared with the Chaetophorales and novel genes acquired through horizontal transfer
Authors: Brouard Jean-Simon , Otis Christian , Lemieux Claude , Turmel Monique
Published: June 2008

Background

To gain insight into the branching order of the five main lineages currently recognized in the green algal class Chlorophyceae and to expand our understanding of chloroplast genome evolution, we have undertaken the sequencing of chloroplast DNA (cpDNA) from representative taxa. The complete cpDNA sequences previously reported for Chlamydomonas (Chlamydomonadales), Scenedesmus (Sphaeropleales), and Stigeoclonium (Chaetophorales) revealed tremendous variability in their architecture, the retention of only few ancestral gene clusters, and derived clusters shared by Chlamydomonas and Scenedesmus. Unexpectedly, our recent phylogenies inferred from these cpDNAs and the partial sequences of three other chlorophycean cpDNAs disclosed two major clades, one uniting the Chlamydomonadales and Sphaeropleales (CS clade) and the other uniting the Oedogoniales, Chaetophorales and Chaetopeltidales (OCC clade). Although molecular signatures provided strong support for this dichotomy and for the branching of the Oedogoniales as the earliest-diverging lineage of the OCC clade, more data are required to validate these phylogenies. We describe here the complete cpDNA sequence of Oedogonium cardiacum (Oedogoniales).

Results

Like its three chlorophycean homologues, the 196,547-bp Oedogonium chloroplast genome displays a distinctive architecture. This genome is one of the most compact among photosynthetic chlorophytes. It has an atypical quadripartite structure, is intron-rich (17 group I and 4 group II introns), and displays 99 different conserved genes and four long open reading frames (ORFs), three of which are clustered in the spacious inverted repeat of 35,493 bp. Intriguingly, two of these ORFs (int and dpoB) revealed high similarities to genes not usually found in cpDNA. At the gene content and gene order levels, the Oedogonium genome most closely resembles its Stigeoclonium counterpart. Characters shared by these chlorophyceans but missing in members of the CS clade include the retention of psaM, rpl32 and trnL(caa), the loss of petA, the disruption of three ancestral clusters and the presence of five derived gene clusters.

Conclusion

The Oedogonium chloroplast genome disclosed additional characters that bolster the evidence for a close alliance between the Oedogoniales and Chaetophorales. Our unprecedented finding of int and dpoB in this cpDNA provides a clear example that novel genes were acquired by the chloroplast genome through horizontal transfers, possibly from a mitochondrial genome donor.
Genome-wide transcriptional changes induced by phagocytosis or growth on bacteria in Dictyostelium
Authors: Sillo Alessio , Bloomfield Gareth , Balest Alessandra , Balbo Alessandra , Pergolizzi Barbara , Peracino Barbara , Skelton Jason , Ivens Alasdair , Bozzaro Salvatore
Published: June 2008

Background

Phagocytosis plays a major role in the defense of higher organisms against microbial infection and provides also the basis for antigen processing in the immune response. Cells of the model organismDictyosteliumare professional phagocytes that exploit phagocytosis of bacteria as the preferred way to ingest food, besides killing pathogens. We have investigatedDictyosteliumdifferential gene expression during phagocytosis of non-pathogenic bacteria, using DNA microarrays, in order to identify molecular functions and novel genes involved in phagocytosis.

Results

The gene expression profiles of cells incubated for a brief time with bacteria were compared with cells either incubated in axenic medium or growing on bacteria. Transcriptional changes during exponential growth in axenic medium or on bacteria were also compared. We recognized 443 and 59 genes that are differentially regulated by phagocytosis or by the different growth conditions (growth on bacteria vs. axenic medium), respectively, and 102 genes regulated by both processes. Roughly one third of the genes are up-regulated compared to macropinocytosis and axenic growth. Functional annotation of differentially regulated genes with different tools revealed that phagocytosis induces profound changes in carbohydrate, aminoacid and lipid metabolism, and in cytoskeletal components. Genes regulating translation and mitochondrial biogenesis are mostly up-regulated. Genes involved in sterol biosynthesis are selectively up-regulated, suggesting a shift in membrane lipid composition linked to phagocytosis. Very few changes were detected in genes required for vesicle fission/fusion, indicating that the intracellular traffic machinery is mostly in common between phagocytosis and macropinocytosis. A few putative receptors, including GPCR family 3 proteins, scaffolding and adhesion proteins, components of signal transduction and transcription factors have been identified, which could be part of a signalling complex regulating phagocytosis and adaptational downstream responses.

Conclusion

The results highlight differences between phagocytosis and macropinocytosis, and provide the basis for targeted functional analysis of new candidate genes and for comparison studies with transcriptomes during infection with pathogenic bacteria.
Mast cell activation is characterized by upregulation of a functional anaphylatoxin C5a receptor
Authors: Soruri Afsaneh , Grigat Jasmin , Kiafard Ziba , Zwirner Jörg
Published: June 2008

Background

Mast cells (MC) are key effector cells of allergic diseases and resistance to helminthic parasites and induce or amplify diverse innate and adaptive immune responses. The signals controlling MC mobilization during inflammation are not fully understood.

Results

Since anaphylatoxins are attractive candidates as MC chemoattractants, we investigated expression and function of anaphylatoxin receptors in murine MC. Precursor cell-derived MC cultured with IL-3 in the presence or absence of SCF did not express significant amounts of surface C5a receptor (C5aR) or C3a receptor (C3aR). MC required approximately 4 h of stimulation with Ag (DNP-albumin, following preincubation with IgE anti-DNP), ionomycin, or PMA to enable a strong chemotactic response towards C5a, paralleled by a distinct C5aR upregulation. Likewise, C5a induced intracellular calcium fluxes solely in activated MC. In contrast, C3a proved to be a weak MC chemotaxin and unable to increase intracellular calcium. Primary peritoneal MC did not express detectable amounts of anaphylatoxin receptors, however, similar to precursor cell-derived MC, stimulation with Ag or ionomycin for 4 h induced a prominent surface expression of C5aR whereas C3aR remained undetectable.

Conclusion

Collectively, our results suggest that Ag-dependent as well as -independent activation induces an inflammatory MC phenotype which is distinguished by neoexpression of a functional C5aR as a novel effector mechanism in MC-mediated pathogenesis.
Mix of methods is needed to identify adverse events in general practice: A prospective observational study
Authors: Wetzels Raymond , Wolters René , van Weel Chris , Wensing Michel
Published: June 2008

Background

The validity and usefulness of incident reporting and other methods for identifying adverse events remains unclear. This study aimed to compare five methods in general practice.

Methods

In a prospective observational study, with five general practitioners, five methods were applied and compared. The five methods were physician reported adverse events, pharmacist reported adverse events, patients' experiences of adverse events, assessment of a random sample of medical records, and assessment of all deceased patients.

Results

A total of 68 events were identified using these methods. The patient survey accounted for the highest number of events and the pharmacist reports for the lowest number. No overlap between the methods was detected. The patient survey accounted for the highest number of events and the pharmacist reports for the lowest number.

Conclusion

A mix of methods is needed to identify adverse events in general practice.
Hepatitis C virus prevalence and genetic diversity among pregnant women in Gabon, central Africa
Authors: Ndong-Atome Guy-Roger , Makuwa Maria , Njouom Richard , Branger Michel , Brun-Vézinet Francoise , Mahé Antoine , Rousset Dominique , Kazanji Mirdad
Published: June 2008

Background

Hepatitis C virus (HCV) infection is a major global public health problem in both developed and developing countries. The prevalence and genetic diversity of HCV in pregnant women in Gabon, central Africa, is not known. We therefore evaluated the prevalence and the circulating genotypes of HCV in a large population cohort of pregnant women.

Methods

Blood samples (947) were collected from pregnant women in the five main cities of the country. The prevalence was evaluated by two ELISA tests, and the circulating genotypes were characterized by sequencing and phylogenetic analysis.

Results

Twenty pregnant women (2.1%) were infected with HCV. The seroprevalence differed significantly by region (p = 0.004) and increased significantly with age (p = 0.05), being 1.3% at 14–20 years, 1.1% at 21–25 years, 1.9% at 26–30 years, 4.1% at 31–35 years and 6.0% at > 35 years. Sequencing in the 5'-UTR and NS5B regions showed that the circulating strains belonged to genotypes 4 (4e and 4c).

Conclusion

We found that the HCV seroprevalence in pregnant women in Gabon is almost as high as that in other African countries and increases with age. Furthermore, only genotype 4 (4e and 4c) was found. More extensive studies aiming to evaluate the prevalence and heterogeneity of HCV genotypes circulating in the general population of the country are needed.
Sensitivity of International Classification of Diseases codes for hyponatremia among commercially insured outpatients in the United States
Authors: Shea Alisa M , Curtis Lesley H , Szczech Lynda A , Schulman Kevin A
Published: June 2008

Background

Administrative claims are a rich source of information for epidemiological and health services research; however, the ability to accurately capture specific diseases or complications using claims data has been debated. In this study, the authors examined the validity of International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis codes for the identification of hyponatremia in an outpatient managed care population.

Methods

We analyzed outpatient laboratory and professional claims for patients aged 18 years and older in the National Managed Care Benchmark Database from Integrated Healthcare Information Services. We obtained all claims for outpatient serum sodium laboratory tests performed in 2004 and 2005, and all outpatient professional claims with a primary or secondary ICD-9-CM diagnosis code of hyponatremia (276.1).

Results

A total of 40,668 outpatient serum sodium laboratory results were identified as hyponatremic (serum sodium < 136 mmol/L). The sensitivity of ICD-9-CM codes for hyponatremia in outpatient professional claims within 15 days before or after the laboratory date was 3.5%. Even for severe cases (serum sodium ≤ 125 mmol/L), sensitivity was < 30%. Specificity was > 99% for all cutoff points.

Conclusion

ICD-9-CM codes in administrative data are insufficient to identify hyponatremia in an outpatient population.
The positive association between number of children and obesity in Iranian women and men: Results from the National Health Survey
Authors: Bakhshi Enayatollah , Eshraghian Mohammad Reza , Mohammad Kazem , Foroushani Abbas Rahimi , Zeraati Hojat , Fotouhi Akbar , Siassi Fraidon , Seifi Behjat
Published: June 2008

Background

To date, few studies have assessed the association between the number of children and obesity in couples. We aimed to investigate this association in men and women aged 20–75 years.

Methods

Data from the National Health Survey were considered in this investigation. It included 2728 women and men (1364 couples) aged 20–75 years. Height and weight were actually measured rather than self-reported. A generalized estimating equation model was used to estimate the odds of obesity (body mass index (BMI ≥ 30)) as a function of the number of children adjusted for age, sex, education, economic index, workforce, smoking and place of residence.

Results

We infer that each additional child has at least 5% and at most 34% increase in the odds of obesity in men and at least 4% and at most 29% increase in the odds of obesity in women. Our test of interaction by sex showed that the association between the number of children and obesity was not different among men and women. Among women, factors that increased obesity included age, low education, having more children, being inactive workforce and being nonsmoker. Among men, these factors included high economic index, low education, having more children, and being nonsmoker.

Conclusion

Our results show an association between the number of children and obesity among men. We would recommend interventions to reduce the number of children to prevent obesity in men.
A simplified guide ruler from numeric table method in doing rotational osteotomy
Authors: Liaw Chen-Kun , Yang Rong-Sen , Hou Sheng-Mou , Wu Tai-Yin , Fuh Chiou-Shann
Published: June 2008

Background

Čobeljić et al. recently reported a numeric table method to provide precise rotational osteotomy which is a well established orthopaedic procedure. The numeric table requires four pages in length that is rather inconvenient during performing an osteotomy operation.

Methods

We thus develop our own method by summarizing the data of the four-page table into a small ruler, which is easy to carry and use in operation room. An electrical version of this ruler is also available. We also build a computer model to verify Čobeljić et al. method.

Results

The error of Čobeljić et al. is between -37% to 16% (mean ± SD = -6% ± 9%). We verify our ruler by calculating the absolute difference between our method and that of Čobeljić et al. The difference is less than 0.1 mm.

Conclusion

Our ruler is convenient for practical use for the rotational osteotomy procedure with equal precision. Further clinical verification is needed to justify its real significance.
Study protocol: The Intensive Care Outcome Network ('ICON') study
Authors: Griffiths John A , Morgan Kayleigh , Barber Vicki S , Young J Duncan
Published: June 2008

Background

Extended follow-up of survivors of ICU treatment has shown many patients suffer long-term physical and psychological consequences that affect their health-related quality of life. The current lack of rigorous longitudinal studies means that the true prevalence of these physical and psychological problems remains undetermined.

Methods/Design

The ICON (Intensive Care Outcome Network) study is a multi-centre, longitudinal study of survivors of critical illness. Patients will be recruited prior to hospital discharge from 20–30 ICUs in the UK and will be assessed at 3, 6, and 12 months following ICU discharge for health-related quality of life as measured by the Short Form-36 (SF-36) and the EuroQoL (EQ-5D); anxiety and depression as measured by the Hospital Anxiety and Depression Scale (HADS); and post traumatic stress disorder (PTSD) symptoms as measured by the PTSD Civilian Checklist (PCL-C). Postal questionnaires will be used.

Discussion

The ICON study will create a valuable UK database detailing the prevalence of physical and psychological morbidity experienced by patients as they recover from critical illness. Knowledge of the prevalence of physical and psychological morbidity in ICU survivors is important because research to generate models of causality, prognosis and treatment effects is dependent on accurate determination of prevalence. The results will also inform economic modelling of the long-term burden of critical illness.

Trial Registration

ISRCTN69112866
Exposure to animals and the risk of allergic asthma: a population-based cross-sectional study in Finnish and Russian children
Authors: Hugg Timo T , Jaakkola Maritta S , Ruotsalainen Risto , Pushkarev Vadim , Jaakkola Jouni JK
Published: June 2008

Background

There is little information on potential differences in animal exposure between Finland and Russia and particularly on the effects of animal exposure on asthma among Russian children. The aim of the study was to compare the pet and farm animal exposures and to assess the relations of pre- and postnatal animal exposures to the occurrence of allergic asthma in Finnish and Russian school children.

Methods

We conducted a population-based cross-sectional study in neighbour towns on either side of the Finnish-Russian border; Imatra in Finland and Svetogorsk in Russia. The study population consisted of 512 Finnish and 581 Russian school children aged 7–16 years (response rate 79%). Multivariate logistic regression analysis was used to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI) related to each exposure.

Results

Current indoor exposure to pets was more frequent among school children in Svetogorsk than in Imatra (67.5% vs. 56.0%, P < 0.001). Finnish children were exposed more frequently to dogs, whereas Russian children to cats during childhood and to farm animals during pregnancy and infancy. The risk of self-reported allergic asthma was inversely related to indoor dog keeping ever in Finland (adjusted OR 0.35, 95% CI 0.13, 0.95), whereas in Russia the risk of allergic asthma was increased in relation to combined indoor cat exposure during infancy and currently (4.56, 1.10, 18.91). The risk of asthma was elevated in relation to contact to farm animals during pregnancy (Finland: 1.95, 0.69, 5.50; Russia: 1.90, 0.70, 5.17) and early life (Finland: 2.05, 0.78, 5.40; Russia: 1.21, 0.39, 3.73).

Conclusion

Exposure to pets and farm animals during childhood differed significantly between Finland and Russia. Our study provides evidence that early-life exposure to cats increases the risk of asthma whereas exposure to dogs is protective. Our findings suggest that intermittent fetal and early-life exposure to farm animals increases the risk of allergic asthma in urban children visiting farms.
Identification of metabolites with anticancer properties by computational metabolomics
Authors: Arakaki Adrian K , Mezencev Roman , Bowen Nathan J , Huang Ying , McDonald John F , Skolnick Jeffrey
Published: June 2008

Background

Certain endogenous metabolites can influence the rate of cancer cell growth. For example, diacylglycerol, ceramides and sphingosine, NAD+ and arginine exert this effect by acting as signaling molecules, while carrying out other important cellular functions. Metabolites can also be involved in the control of cell proliferation by directly regulating gene expression in ways that are signaling pathway-independent, e.g. by direct activation of transcription factors or by inducing epigenetic processes. The fact that metabolites can affect the cancer process on so many levels suggests that the change in concentration of some metabolites that occurs in cancer cells could have an active role in the progress of the disease.

Results

CoMet, a fully automated Computational Metabolomics method to predict changes in metabolite levels in cancer cells compared to normal references has been developed and applied to Jurkat T leukemia cells with the goal of testing the following hypothesis: Up or down regulation in cancer cells of the expression of genes encoding for metabolic enzymes leads to changes in intracellular metabolite concentrations that contribute to disease progression. All nine metabolites predicted to be lowered in Jurkat cells with respect to lymphoblasts that were examined (riboflavin, tryptamine, 3-sulfino-L-alanine, menaquinone, dehydroepiandrosterone, α-hydroxystearic acid, hydroxyacetone, seleno-L-methionine and 5,6-dimethylbenzimidazole), exhibited antiproliferative activity that has not been reported before, while only two (bilirubin and androsterone) of the eleven tested metabolites predicted to be increased or unchanged in Jurkat cells displayed significant antiproliferative activity.

Conclusion

These results: a) demonstrate that CoMet is a valuable method to identify potential compounds for experimental validation, b) indicate that cancer cell metabolism may be regulated to reduce the intracellular concentration of certain antiproliferative metabolites, leading to uninhibited cellular growth and c) suggest that many other endogenous metabolites with important roles in carcinogenesis are awaiting discovery.
Integrative genomics analysis of chromosome 5p gain in cervical cancer reveals target over-expressed genes, including Drosha
Authors: Scotto Luigi , Narayan Gopeshwar , Nandula Subhadra V , Subramaniyam Shivakumar , Kaufmann Andreas M , Wright Jason D , Pothuri Bhavana , Mansukhani Mahesh , Schneider Achim , Arias-Pulido Hugo , Murty Vundavalli V
Published: June 2008

Background

Copy number gains and amplifications are characteristic feature of cervical cancer (CC) genomes for which the underlying mechanisms are unclear. These changes may possess oncogenic properties by deregulating tumor-related genes. Gain of short arm of chromosome 5 (5p) is the most frequent karyotypic change in CC.

Methods

To examine the role of 5p gain, we performed a combination of single nucleotide polymorphism (SNP) array, fluorescence in situ hybridization (FISH), and gene expression analyses on invasive cancer and in various stages of CC progression.

Results

The SNP and FISH analyses revealed copy number increase (CNI) of 5p in 63% of invasive CC, which arises at later stages of precancerous lesions in CC development. We integrated chromosome 5 genomic copy number and gene expression data to identify key target over expressed genes as a consequence of 5p gain. One of the candidates identified was Drosha (RNASEN), a gene that is required in the first step of microRNA (miRNA) processing in the nucleus. Other 5p genes identified as targets of CNI play a role in DNA repair and cell cycle regulation (BASP1, TARS, PAIP1, BRD9, RAD1, SKP2, and POLS), signal transduction (OSMR), and mitochondrial oxidative phosphorylation (NNT, SDHA, and NDUFS6), suggesting that disruption of pathways involving these genes may contribute to CC progression.

Conclusion

Taken together, we demonstrate the power of integrating genomics data with expression data in deciphering tumor-related targets of CNI. Identification of 5p gene targets in CC denotes an important step towards biomarker development and forms a framework for testing as molecular therapeutic targets.
Coxsackievirus and adenovirus receptor expression in human endometrial adenocarcinoma: possible clinical implications
Authors: Giaginis Costas T , Zarros Apostolos C , Papaefthymiou Maria A , Papadopouli Aikaterini E , Sfiniadakis Ioannis K , Theocharis Stamatios E
Published: June 2008

The coxsackievirus and adenovirus receptor (CAR) is a crucial receptor for the entry of both coxsackie B viruses and adenoviruses into host cells. CAR expression on tumor cells was reported to be associated with their sensitivity to adenoviral infection, while it was considered as a surrogate marker for monitoring and/or predicting the outcome of adenovirus-mediated gene therapy. The aim of the present study was to evaluate the clinical significance of CAR expression in endometrial adenocarcinoma. CAR expression was assessed immunohistochemically in tumoral samples of 41 endometrial adenocarcinoma patients and was statistically analyzed in relation to various clinicopathological parameters, tumor proliferative capacity and patient survival. CAR positivity was noted in 23 out of 41 (56%) endometrial adenocarcinoma cases, while high CAR expression in 8 out of 23 (35%) positive ones. CAR intensity of immunostaining was classified as mild in 11 (48%), moderate in 10 (43%) and intense in 2 (9%) out of the 23 positive cases. CAR positivity was significantly associated with tumor histological grade (p = 0.036), as well differentiated tumors more frequently demonstrating no CAR expression. CAR staining intensity was significantly associated with tumor histological type (p = 0.016), as tumors possessing squamous elements presented more frequently intense CAR immunostaining. High CAR expression showed a trend to be correlated with increased tumor proliferative capacity (p = 0.057). Patients with tumors presenting moderate or intense CAR staining intensity were characterized by longer survival times than those with mild one; however, this difference did not reach statistical significance. These data reveal, for the first time, the expression of CAR in clinical material obtained from patients with endometrial adenocarcinoma in relation to important clinicopathological parameters for their management. As CAR appears to modulate the proliferation and characteristics of cancer cells, its expression could be considered of possible clinical importance for future (gene) therapy applications.