bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparison of genomic and proteomic data in recurrent airway obstruction affected horses using ingenuity pathway analysis®
Authors: Racine Julien , Gerber Vinzenz , Miskovic Feutz Marybeth , Riley C Paige , Adamec Jiri , Swinburne June E , Couetil Laurent L 
Published: August 2011

Abstract

Background
Recurrent airway obstruction (RAO) is a severe chronic respiratory disease affecting horses worldwide, though mostly in the Northern hemisphere. Environmental as well as genetic factors strongly influence the course and prognosis of the disease. Research has been focused on characterization of immunologic factors contributing to inflammatory responses, on genetic linkage analysis, and, more recently, on proteomic analysis of airway secretions from affected horses. The goal of this study was to investigate the interactions between eight candidate genes previously identified in a genetic linkage study and proteins expressed in bronchoalveolar lavage fluid (BALF) collected from healthy and RAO-affected horses. The analysis was carried out with Ingenuity Pathway Analysis® bioinformatics software.

Results
The gene with the greatest number of indirect interactions with the set of proteins identified is Interleukin 4 Receptor (IL-4R), whose protein has also been detected in BALF. Interleukin 21 receptor and chemokine (C-C motif) ligand 24 also showed a large number of interactions with the group of detected proteins. Protein products of other genes like that of SOCS5, revealed direct interactions with the IL-4R protein. The interacting proteins NOD2, RPS6KA5 and FOXP3 found in several pathways are reported regulators of the NFκB pathway.

Conclusions
The pathways generated with IL-4R highlight possible important intracellular signaling cascades implicating, for instance, NFκB. Furthermore, the proposed interaction between SOCS5 and IL-4R could explain how different genes can lead to identical clinical RAO phenotypes, as observed in two Swiss Warmblood half sibling families because these proteins interact upstream of an important cascade where they may act as a functional unit.
Global organization of protein complexome in the yeast Saccharomyces cerevisiae
Authors: Lee Sang Hoon , Kim Pan-Jun , Jeong Hawoong 
Published: August 2011

Abstract

Background
Proteins in organisms, rather than act alone, usually form protein complexes to perform cellular functions. We analyze the topological network structure of protein complexes and their component proteins in the budding yeast in terms of the bipartite network and its projections, where the complexes and proteins are its two distinct components. Compared to conventional protein-protein interaction networks, the networks from the protein complexes show more homogeneous structures than those of the binary protein interactions, implying the formation of complexes that cause a relatively more uniform number of interaction partners. In addition, we suggest a new optimization method to determine the abundance and function of protein complexes, based on the information of their global organization. Estimating abundance and biological functions is of great importance for many researches, by providing a quantitative description of cell behaviors, instead of just a "catalogues" of the lists of protein interactions.

Results
With our new optimization method, we present genome-wide assignments of abundance and biological functions for complexes, as well as previously unknown abundance and functions of proteins, which can provide significant information for further investigations in proteomics. It is strongly supported by a number of biologically relevant examples, such as the relationship between the cytoskeleton proteins and signal transduction and the metabolic enzyme Eno2's involvement in the cell division process.

Conclusions
We believe that our methods and findings are applicable not only to the specific area of proteomics, but also to much broader areas of systems biology with the concept of optimization principle.
Lobar pneumonia caused by Ralstonia pickettii in a sixty-five-year-old Han Chinese man: a case report
Authors: Pan Wensen , Zhao Zhiming , Dong Mei 
Published: August 2011

Abstract

Introduction

Ralstonia pickettii is a gram-negative, oxidase-positive bacillus and is an emerging pathogen found in infections described in hospital settings. The cases reported in the literature mostly are nosocomial infections due to contaminated blood products, sterile water, saline, treatment fluids and venous catheters. Human infection unrelated to contaminated solutions is rare. We report a case of lobar pneumonia and pulmonary abscess caused by Ralstonia pickettii in an older patient.

Case presentation
A sixty-five-year old Han Chinese man presented having had cough, expectoration, chest pain and fever lasting for twenty days. His medical history was notable for hypertension over the previous ten years, and the habit of smoking for forty years. A thoracic computed tomography scan supported the diagnosis of right-sided lobar pneumonia. A lung biopsy was done and pathological analysis confirmed lobar pneumonia. Two lung biopsy specimens from separate sites grew Ralstonia pickettii. After six days, a repeat thoracic scan revealed a right-sided abscess. A thoracentesis was performed and the purulent fluid grew Ralstonia pickettii. The chest tube remained inserted to rinse the cavity with sterile sodium chloride. He received an antibiotic course of intravenous cefoperazone sodium-sulbactam sodium for eighteen days and imipenem-cilastatin for twelve days. A repeat chest X-ray revealed resolution of the pulmonary abscess and improvement of pneumonia. He remained afebrile and free of respiratory symptoms after treatments.

Conclusion
This case demonstrates a Ralstonia pickettii infection in the absence of an obvious nosocomial source. It is possible that such cases will become common in the future. Therefore, further studies are needed to evaluate its sensitivity to common antibiotics.
HIF-1α effects on angiogenic potential in human small cell lung carcinoma
Authors: Wan Jun , Chai Huiping , Yu Zaicheng , Ge Wei , Kang Ningning , Xia Wanli , Che Yun 
Published: August 2011

Abstract

Background
Hypoxia-inducible factor-1 alpha (HIF-1α) maybe an important regulatory factor for angiogenesis of small cell lung cancer (SCLC). Our study aimed to investigate the effect of HIF-1α on angiogenic potential of SCLC including two points: One is the effect of HIF-1α on the angiogenesis of SCLC in vivo. The other is the regulation of angiogenic genes by HIF-1α in vitro and in vivo.

Methods

In vivo we used an alternative method to study the effect of HIF-1a on angiogenic potential of SCLC by buliding NCI-H446 cell transplantation tumor on the chick embryo chorioallantoic membrane (CAM) surface. In vitro we used microarray to screen out the angiogenic genes regulated by HIF-1a and tested their expression level in CAM transplantation tumor by RT-PCR and Western-blot analysis.

Results

In vivo angiogenic response surrounding the SCLC transplantation tumors in chick embryo chorioallantoic membrane (CAM) was promoted after exogenous HIF-1α transduction (p < 0.05). In vitro the changes of angiogenic genes expression induced by HIF-1α in NCI-H446 cells were analyzed by cDNA microarray experiments. HIF-1α upregulated the expression of angiogenic genes VEGF-A, TNFAIP6, PDGFC, FN1, MMP28, MMP14 to 6.76-, 6.69-, 2.26-, 2.31-, 4.39-, 2.97- fold respectively and glycolytic genes GLUT1, GLUT2 to2.98-, 3.74- fold respectively. In addition, the expression of these angiogenic factors were also upregulated by HIF-1α in the transplantion tumors in CAM as RT-PCR and Western-blot analysis indicated.

Conclusions
These results indicated that HIF-1α may enhance the angiogenic potential of SCLC by regulating some angiogenic genes such as VEGF-A, MMP28 etc. Therefore, HIF-1α may be a potential target for the gene targeted therapy of SCLC.
Bendamustine Combined With Rituximab in Patients With Relapsed and/or Refractory Chronic Lymphocytic Leukemia: A Multicenter Phase II Trial of the German Chronic Lymphocytic Leukemia Study Group
Authors: Fischer Kirsten , Cramer Paula , Busch Raymonde , Stilgenbauer Stephan , Bahlo Jasmin , Schweighofer Carmen D. , Böttcher Sebastian , Staib Peter , Kiehl Michael , Eckart Michael J. , Kranz Gabriele , Goede Valentin , Elter Thomas , Bühler Andreas , Winkler Dirk , Kneba Michael , Döhner Hartmut , Eichhorst Barbara F. , Hallek Michael , Wendtner Clemens-Martin 
Published: August 2011

Purpose The objective of this trial was to evaluate safety and efficacy of bendamustine combined with rituximab (BR) in patients with relapsed and/or refractory chronic lymphocytic leukemia (CLL). Patients and Methods Seventy-eight patients, including 22 patients with fludarabine-refractory disease (28.2%) and 14 patients (17.9%) with deletion of 17p, received BR chemoimmunotherapy. Bendamustine was administered at a dose of 70 mg/m2 on days 1 and 2 combined with rituximab 375 mg/m2 on day 0 of the first course and 500 mg/m2 on day 1 during subsequent courses for up to six courses. Results On the basis of intent-to-treat analysis, the overall response rate was 59.0% (95% CI, 47.3% to 70.0%). Complete response, partial response, and nodular partial response were achieved in 9.0%, 47.4%, and 2.6% of patients, respectively. Overall response rate was 45.5% in fludarabine-refractory patients and 60.5% in fludarabine-sensitive patients. Among genetic subgroups, 92.3% of patients with del(11q), 100% with trisomy 12, 7.1% with del(17p), and 58.7% with unmutated IGHV status responded to treatment. After a median follow-up time of 24 months, the median event-free survival was 14.7 months. Severe infections occurred in 12.8% of patients. Grade 3 or 4 neutropenia, thrombocytopenia, and anemia were documented in 23.1%, 28.2%, and 16.6% of patients, respectively. Conclusion Chemoimmunotherapy with BR is effective and safe in patients with relapsed CLL and has notable activity in fludarabine-refractory disease. Major but tolerable toxicities were myelosuppression and infections. These promising results encouraged us to initiate a further phase II trial evaluating the BR regimen in patients with previously untreated CLL.
Estimating the Probability of Abusive Head Trauma: A Pooled Analysis
Authors: Maguire Sabine Ann , Kemp Alison Mary , Lumb Rebecca Caroline , Farewell Daniel Mark 
Published: August 2011

CONTEXT AND OBJECTIVE:To determine which combinations of clinical features assist in distinguishing abusive head trauma (AHT) from nonabusive head trauma.METHODS:Individual patient data from 6 comparative studies of children younger than 3 years with intracranial injury were analyzed to determine the association between AHT and combinations of apnea; retinal hemorrhage; rib, skull, and long-bone fractures; seizures; and head and/or neck bruising. An aggregate analysis of data from these studies used multiple imputation of combined clinical features using a bespoke hotdeck imputation strategy, which accounted for uncertainty arising from missing information.RESULTS:Analyzing 1053 children (348 had AHT), excluding nonsignificant variables (gender, age, skull fractures), for a child with an intracranial injury and 1 or 2 of the 6 features, the positive predictive value (PPV) of AHT varies from 4% to 97% according to the different combinations. Although rarely recorded, apnea is significantly associated with AHT (odds ratio [OR]: 6.89 [confidence interval: 2.08–22.86]). When rib fracture or retinal hemorrhage was present with any 1 of the other features, the OR for AHT is &gt;100 (PPV &gt; 85%). Any combination of 3 or more of the 6 significant features yielded an OR of &gt;100 (PPV for AHT &gt; 85%).CONCLUSIONS:Probabilities of AHT can be estimated on the basis of different combinations of clinical features. The model could be further developed in a prospective large-scale study, with an expanded clinical data set, to contribute to a more refined tool to inform clinical decisions about the likelihood of AHT.
Multiple OralCandidaInfections in Patients with Sjögren’s Syndrome — Prevalence and Clinical and Drug Susceptibility Profiles
Authors: YAN ZHIMIN , YOUNG ANDREW L. , HUA HONG , XU YANYING 
Published: August 2011

Objective.To determine the prevalence of oral candidiasis and multiple oralCandidainfections in patients with primary Sjögren’s syndrome (SS), and the clinical and drug susceptibility profile.Methods.Thirty patients with primary SS were enrolled in our study. The diagnosis of oral candidiasis was based on the clinical manifestation, and confirmed by a concentrated rinse culture.Candidaspp. assessment was accomplished using standard methods: Sabouraud dextrose agar with 50 mg/l chloramphenicol and CHROMagar were used for the rapid screening of clinical species, followed by the API 20C system for further species identification.In vitroantifungal drug susceptibility ofCandidaisolates was determined by the minimal inhibitory concentrations.Results.In our study, 87% (26/30) of subjects had oral candidiasis, in which 42% (11/26) had multipleCandidaspp. infection. AlthoughC. albicansremains the predominant isolate, other rare species such asC. tropicalis,C. glabrata,C. parapsilosis, andC. kruseiwere present, alone or in combination. Chronic atrophic candidiasis is the most common clinical type of oral candidiasis in patients with SS. The susceptibilities of the 44Candidaisolates to 7 antifungal agents varied dramatically. The resistance to azoles was remarkable, and the phenomenon of cross-resistance between itraconazole and fluconazole was observed.Conclusion.Patients with primary SS carry a high risk of oral candidiasis and a high frequency of multipleCandidainfections. The azole resistance patterns ofCandidaspp. support the necessity for drug susceptibility testing as a routine procedure for patients with oralCandidainfections.
Associations of Vitamin D Binding Protein Gene Polymorphisms with the Development of Peripheral Arthritis and Uveitis in Ankylosing Spondylitis
Authors: JUNG KYONG-HEE , KIM TAE-HWAN , SHEEN DONG-HYUK , LIM MI-KYOUNG , LEE SANG-KWANG , KIM JI-YOUNG , PARK HYO , CHAE SOO-CHEON , SHIM SEUNG-CHEOL 
Published: August 2011

Objective.Genetic factors account for more than 90% of overall susceptibility to ankylosing spondylitis (AS), and recent studies have focused on non-major histocompatibility complex genes. Vitamin D binding protein (DBP) is a highly polymorphic protein that transports vitamin D and its metabolites. In addition to its sterol binding capacity, DBP has many other roles in the inflammatory and immune systems, and has been reported to be associated with autoimmune diseases. We investigated the association between DBP polymorphisms and susceptibility to AS.Methods.This case-control study was conducted in 223 patients with AS and 239 ethnically matched controls who were genotyped for 8 single-nucleotide polymorphisms (SNP) in the DBP and its promoter. Genomic DNA was isolated from peripheral blood leukocytes using the standard phenolchloroform method, and the GoldenGate assay was used for genotyping.Results.No significant association was found between the susceptibility to AS and DBP polymorphisms. In a subgroup analysis of patients with AS, G alleles at rs222016 and rs222020 (OR 0.63, 95% CI 0.42–0.95, p = 0.03; OR 0.63, 95% CI 0.42–0.95, p = 0.03, respectively) and A allele at rs3733359 (OR 0.59, 95% CI 0.39–0.90, p = 0.01) showed the decreased risk of peripheral arthritis. G allele at rs4752 showed increased risk of uveitis (OR 2.04, 95% CI 1.12–3.72, p = 0.02). On the haplotype analyses, haplotype 2 (AGGA) protected against the development of peripheral arthritis (p = 0.01) and haplotype 3 (GAAG) was associated with an increased likelihood of uveitis (p = 0.02).Conclusion.DBP gene polymorphisms are associated with the development of peripheral arthritis and uveitis in Korean patients with AS. Given the influence of different DBP variants on the immune system, larger-scale studies are warranted to elucidate the role of DBP in the pathogenesis of AS.
Mortality in Patients with Biopsy-proven Giant Cell Arteritis: A South Australian Population-based Study
Authors: NINAN JEM , NGUYEN ANH-MINH , COLE ANTONIA , RISCHMUELLER MAUREEN , DODD THOMAS , ROBERTS-THOMSON PETER , HILL CATHERINE L. 
Published: August 2011

Objective.To compare mortality rates and cause of death in patients with biopsy-proven giant cell arteritis (GCA) with those in the general population.Methods.Patients with biopsy-proven GCA were identified from pathology reports of temporal artery biopsies in South Australia, from January 1, 1992, to December 31, 2006. All patients with biopsy-proven GCA were linked to the South Australian Births, Death and Marriage Registry to identify deaths until December 31, 2006. Standardized mortality ratios and relative survival (ratio of observed survival in GCA group to expected survival of general South Australian population, matched by age, sex, and calendar time) were calculated. The cause of death recorded on the death certificate was also documented.Results.There were 225 cases of biopsy-proven GCA (163 women and 62 men). The mean age at diagnosis of GCA was 78.2 years. The mean followup period was 66.2 months (SD 47.1 mo). During the followup period, there were 71 deaths in the GCA group (50 women, 21 men). The standardized mortality ratio was 0.99 (95% CI 0.77–1.25). The relative survival for different followup periods demonstrates that patients with GCA experienced similar mortality to the general population (age-matched and sex-matched). Death from cardiovascular causes (45%) was the most common, followed by infection (17%) and cancer (17%). Infection was a significantly more common cause of death in the first year (chi-squared, p = 0.0002).Conclusion.Our population-based cohort study did not demonstrate any increased mortality risk for patients diagnosed with biopsy-proven GCA. The risk of death from infection early in the disease may be increased.
Tumor Necrosis Factor-blocking Agents for Children with Enthesitis-related Arthritis — Data from the Dutch Arthritis and Biologicals in Children Register, 1999–2010
Authors: OTTEN MARIEKE H. , PRINCE FEMKE H.M. , TWILT MARINKA , ten CATE REBECCA , ARMBRUST WINEKE , HOPPENREIJS ESTHER P.A.H. , KOOPMAN-KEEMINK YVONNE , WULFFRAAT NICO M. , GORTER SIMONE L. , DOLMAN KOERT M. , SWART JOOST F. , van den BERG J. MERLIJN , van ROSSUM MARION A.J. , van SUIJLEKOM-SMIT LISETTE W.A. 
Published: August 2011

Objective.To evaluate the effectiveness and safety of biological agents in children with enthesitis-related arthritis (ERA).Methods.All patients with ERA in whom a biological agent was initiated between 1999 and 2010 were selected from the Dutch Arthritis and Biologicals in Children (ABC) register. In this ongoing multicenter observational register, data on the course of the disease and medication use are retrieved prospectively at the start of the biological agent, after 3 months, and yearly thereafter. Inactive disease was assessed in accordance with the Wallace criteria.Results.Twenty-two patients with ERA started taking 1 or more biological agents: 20 took etanercept, 2 took adalimumab (1 switched from etanercept to adalimumab), and 2 took infliximab (1 switched from etanercept to infliximab). Characteristics: 77% were male, 77% had enthesitis, 68% were HLA-B27-positive. The median age of onset was 10.4 (IQR 9.4–12.0) years; median followup from the start of the biological agent was 1.2 (IQR 0.5–2.4) years. Intention-to-treat analysis shows that inactive disease was achieved in 7 of 22 patients (32%) after 3 months, 5 of 13 patients (38%) after 15 months, and 5 of 8 patients (63%) after 27 months of treatment. Two patients discontinued etanercept because of ineffectiveness, and switched to adalimumab (inactive disease achieved) or infliximab (decline in joints with arthritis after 3 months of treatment). One patient discontinued etanercept because of remission, but had flare and restarted treatment, with good clinical response. No serious adverse events occurred.Conclusion.Tumor necrosis factor (TNF)-blocking agents seem effective and safe for patients with ERA that was previously unresponsive to 1 or more DMARD. However, a sustained disease-free state could not be achieved, and none discontinued TNF-blocking agents successfully.
Nephrotic Syndrome and Subepithelial Deposits in a Mouse Model of Immune-Mediated Anti-Podocyte Glomerulonephritis
Authors: Meyer-Schwesinger Catherine , Dehde Silke , Klug Philipp , Becker Jan U. , Mathey Sabrina , Arefi Kazem , Balabanov Stefan , Venz Simone , Endlich Karl-Hans , Pekna Marcela , Gessner J. Engelbert , Thaiss Friedrich , Meyer Tobias N. 
Published: August 2011

Abstract
Subepithelial immune complex deposition in glomerular disease causes local inflammation and proteinuria by podocyte disruption. A rat model of membranous nephropathy, the passive Heymann nephritis, suggests that Abs against specific podocyte Ags cause subepithelial deposit formation and podocyte foot process disruption. In this study, we present a mouse model in which a polyclonal sheep anti-mouse podocyte Ab caused subepithelial immune complex formation. Mice developed a nephrotic syndrome with severe edema, proteinuria, hypoalbuminemia, and elevated cholesterol and triglycerides. Development of proteinuria was biphasic: an initial protein loss was followed by a second massive increase of protein loss beginning at approximately day 10. By histology, podocytes were swollen. Electron microscopy revealed 60–80% podocyte foot process effacement and subepithelial deposits, but no disruption of the glomerular basement membrane. Nephrin and synaptopodin staining was severely disrupted, and podocyte number was reduced in anti-podocyte serum-treated mice, indicating severe podocyte damage. Immunohistochemistry detected the injected anti-podocyte Ab exclusively along the glomerular filtration barrier. Immunoelectron microscopy localized the Ab to podocyte foot processes and the glomerular basement membrane. Similarly, immunohistochemistry localized mouse IgG to the subepithelial space. The third complement component (C3) was detected in a linear staining pattern along the glomerular basement membrane and in the mesangial hinge region. However, C3-deficient mice were not protected from podocyte damage, indicating a complement-independent mechanism. Twenty proteins were identified as possible Ags to the sheep anti-podocyte serum by mass spectrometry. Together, these data establish a reproducible model of immune-mediated podocyte injury in mice with subepithelial immune complex formation.
IL-12p35 Subunit Contributes to Autoimmunity by Limiting IL-27–Driven Regulatory Responses
Authors: Vasconcellos Rita , Carter Natalie A. , Rosser Elizabeth C. , Mauri Claudia 
Published: August 2011

Abstract
Contrasting results have emerged from studies performed using IL-12p35−/− mice. Animals lacking the IL-12p35 subunit can either be protected from or develop exacerbated autoimmune diseases, intracellular infections, and delayed-type hypersensitivity responses. In this study, we report that mice lacking the IL-12p35 subunit develop a significantly milder Ag-induced arthritis compared with wild-type (WT) mice. Lack of severe inflammation is accompanied by an increase in the mRNA levels of the Ebi-3 and p28 subunits and increased secretion of IL-27 and IL-10. This anti-inflammatory environment contributed to increased differentiation of regulatory T and B cells with intact suppressive function. Furthermore, IL-12p35−/− mice display reduced numbers of Th17 cells compared with WT arthritic mice. Neutralization of IL-27, but not the systemic administration of IL-12, restored inflammation and Th17 to levels seen in WT mice. The restoration of disease phenotype after anti–IL-27 administration indicates that the IL-12p35 subunit acts as negative regulator of the developing IL-27 response in this model of arthritis.