bluuebunny/crossref_metadata_2025_split huggingface dataset:
Comparative virulence of in vitro‐cultured primate‐ and pig‐associated Helicobacter suis strains in a BALB/c mouse and a Mongolian gerbil model
Authors: Bosschem Iris , Flahou Bram , Bakker Jaco , Heuvelman Edwin , Langermans Jan A.M. , De Bruyne Ellen , Joosten Myrthe , Smet Annemieke , Ducatelle Richard , Haesebrouck Freddy 
Published: August 2016

AbstractBackgroundHelicobacter suis (H. suis) is the most prevalent gastric non‐H. pylori Helicobacter species in humans. This bacterium mainly colonizes the stomach of pigs, but it has also been detected in the stomach of nonhuman primates. The aim of this study was to obtain better insights into potential differences between pig‐ and primate‐associated H. suis strains in virulence and pathogenesis.Materials and MethodsIn vitro‐isolated H. suis strains obtained from pigs, cynomolgus monkeys (Macaca fascicularis), and rhesus monkeys (Macaca mulatta) were used for intragastric inoculation of BALB/c mice and Mongolian gerbils. Nine weeks and six months later, samples of the stomach of inoculated and control animals were taken for PCR analysis and histopathological examination.ResultsThe cynomolgus monkey‐associated H. suis strain only colonized the stomach of mice, but not of Mongolian gerbils. All other H. suis strains colonized the stomach in both rodent models. In all colonized animals, severe gastric inflammation was induced. Gastric lymphoid follicles and destruction of the antral epithelium were observed in infected gerbils, but not in mice. Infection with both pig‐ and primate‐associated H. suis strains evoked a similar marked Th17 response in mice and gerbils, accompanied by increased CXCL‐13 expression levels.ConclusionsApart from the cynomolgus monkey‐associated strain which was unable of colonizing the stomach of Mongolian gerbils, no substantial differences in virulence were found in rodent models between in vitro‐cultured pig‐associated, cynomolgus monkey‐associated and rhesus monkey‐associated H. suis strains. The experimental host determines the outcome of the immune response against H. suis infection, rather than the original host.
Prognostic value of the albumin–bilirubin grade in patients with hepatocellular carcinoma: Validation in a Chinese cohort
Authors: Li Mu‐xing , Zhao Hong , Bi Xin‐yu , Li Zhi‐yu , Huang Zhen , Han Yue , Zhou Jian‐guo , Zhao Jian‐jun , Zhang Ye‐fan , Cai Jian‐qiang 
Published: August 2016

AimThe prognostic value of the newly raised objective liver function assessment tool, the albumin–bilirubin (ALBI) grade, in patients with hepatocellular carcinoma has not been fully validated. We aimed to compare the performance of ALBI grade with the specific Child–Pugh (C‐P) score in predicting prognosis in this study.MethodsThe clinical data of 491 C‐P class A patients who underwent liver resection as initial therapy from January 2000 to December 2007 in Cancer Hospital, Chinese Academy of Medical Sciences (Beijing, China) were retrospectively analyzed. The prognostic performances of ALBI and C‐P score in predicting the short‐ and long‐term clinical outcomes were compared.ResultsThe ALBI score gained a significantly larger area under the receiver operating characteristic curve for predicting the occurrence of severe postoperative complications than that of C‐P score. With a median follow‐up of 57 months, the 1‐year, 3‐year, and 5‐year overall survival rates of the patients were 92.1%, 65.8%, and 45.2%, respectively. Tumor number, tumor size, and ALBI grade were proved to be the independent prognostic factors for overall survival in the multivariate analysis. Prognostic performance was shown to be better for ALBI grade when it was compared to C‐P score in terms of both the Akaike information criterion value and χ2 value of likelihood ratio test.ConclusionsThe ALBI grade, which was featured by simplicity and objectivity, gained a superior prognostic value than that of C‐P grade in patients with hepatocellular carcinoma who underwent liver resection. Future well‐designed studies with larger sample sizes are warranted.
Sociodemographic associations of 4‐year overweight and obese incidence among a racially diverse cohort of healthy weight 18‐year‐olds
Authors: Young D. R. , Koebnick C. , Hsu J. ‐W. Y. 
Published: August 2016

SummaryBackgroundEmerging adulthood is a critical time for excess weight gain. Risk can be masked if recommended overweight and obesity cut‐points for Asians are not employed.ObjectivesTo determine the associations among sociodemographic factors and occurrence of overweight and obesity among normal weight 18‐year olds.MethodsNormal weight (body mass index < 25 kg m−2; <23 kg m−2 for Asians) 18‐year‐old (9037 boys, 13 786 girls, 36% Hispanic, 34% non‐Hispanic Whites, 10% Black, 5% Asian) members of a healthcare organization in 2008 were followed through 2012 to identify incidence of overweight and obesity. Hazard ratios (HR) and 95% confidence intervals (CI) were determined controlling for sex, race/ethnicity, neighbourhood education, neighbourhood income and smoking status.ResultsAfter 3 years of follow‐up, the HR for overweight was 1.28 (95% CI: 1.12, 1.45) in the lowest quartile of neighbourhood education compared with the highest. Asians and Pacific Islanders had greater risk of overweight (HR 2.89, 95% CI: 2.55, 3.28; HR 3.13, 95% CI 2.23, 4.38) than non‐Hispanic Whites. Girls and Blacks were more likely to become obese than boys and non‐Hispanic Whites, as were those living in the lowest neighbourhood education quartile and lower neighbourhood income quartiles.ConclusionsGirls, Asians, Blacks and those living in low education and income neighbourhoods during adolescence are at risk for excessive weight gain trajectories.
Chloride flux in phagocytes
Authors: Wang Guoshun 
Published: August 2016

SummaryPhagocytes, such as neutrophils and macrophages, engulf microbes into phagosomes and launch chemical attacks to kill and degrade them. Such a critical innate immune function necessitates ion participation. Chloride, the most abundant anion in the human body, is an indispensable constituent of the myeloperoxidase (MPO)–H2O2–halide system that produces the potent microbicide hypochlorous acid (HOCl). It also serves as a balancing ion to set membrane potentials, optimize cytosolic and phagosomal pH, and regulate phagosomal enzymatic activities. Deficient supply of this anion to or defective attainment of this anion by phagocytes is linked to innate immune defects. However, how phagocytes acquire chloride from their residing environment especially when they are deployed to epithelium‐lined lumens, and how chloride is intracellularly transported to phagosomes remain largely unknown. This review article will provide an overview of chloride protein carriers, potential mechanisms for phagocytic chloride preservation and acquisition, intracellular chloride supply to phagosomes for oxidant production, and methods to measure chloride levels in phagocytes and their phagosomes.
Neutral serine proteases of neutrophils
Authors: Kettritz Ralph 
Published: August 2016

SummaryNeutrophil serine proteases (NSPs) exercise tissue‐degrading and microbial‐killing effects. The spectrum of NSP‐mediated functions grows continuously, not least because of methodological progress. Sensitive and specific FRET substrates were developed to study the proteolytic activity of each NSP member. Advanced biochemical methods are beginning to characterize common and specific NSP substrates. The resulting novel information indicates that NSPs contribute not only to genuine inflammatory neutrophil functions but also to autoimmunity, metabolic conditions, and cancer. Tight regulatory mechanisms control the proteolytic potential of NSPs. However, not all NSP functions depend on their enzymatic activity. Proteinase‐3 (PR3) is somewhat unique among the NSPs for PR3 functions as an autoantigen. Patients with small‐vessel vasculitis develop autoantibodies to PR3 that bind their target antigens on the neutrophil surface and trigger neutrophil activation. These activated cells subsequently contribute to vascular necrosis with life‐threatening multiorgan failure. This article discusses various aspects of NSP biology and highlights translational aspects with strong clinical implications.
Neutrophils in cancer
Authors: Treffers Louise W. , Hiemstra Ida H. , Kuijpers Taco W. , van den Berg Timo K. , Matlung Hanke L. 
Published: August 2016

SummaryNeutrophils play an important role in cancer. This does not only relate to the well‐established prognostic value of the presence of neutrophils, either in the blood or in tumor tissue, in the context of cancer progression or for the monitoring of therapy, but also to their active role in the progression of cancer. In the current review, we describe what is known in general about the role of neutrophils in cancer. What is emerging is a complex, rather heterogeneous picture with both pro‐ and anti‐tumorigenic roles, which apparently differs with cancer type and disease stage. Furthermore, we will discuss the well‐known role of neutrophils as myeloid‐derived suppressor cells (MDSC), and also on the role of neutrophils as important effector cells during antibody therapy in cancer. It is clear that neutrophils contribute substantially to cancer progression in multiple ways, and this includes both direct effects on the cancer cells and indirect effect on the tumor microenvironment. While in many cases neutrophils have been shown to promote tumor progression, for instance by acting as MDSC, there are also protective effects, particularly when antibody immunotherapy is performed. A better understanding of the role of neutrophils is likely to provide opportunities for immunomodulation and for improving the treatment of cancer patients.
Multifaceted effects of Francisella tularensis on human neutrophil function and lifespan
Authors: Kinkead Lauren C. , Allen Lee‐Ann H. 
Published: August 2016

SummaryFrancisella tularensis in an intracellular bacterial pathogen that causes a potentially lethal disease called tularemia. Studies performed nearly 100 years ago revealed that neutrophil accumulation in infected tissues correlates directly with the extent of necrotic damage during F. tularensis infection. However, the dynamics and details of bacteria–neutrophil interactions have only recently been studied in detail. Herein, we review current understanding regarding the mechanisms that recruit neutrophils to F. tularensis–infected lungs, opsonization and phagocytosis, evasion and inhibition of neutrophil defense mechanisms, as well as the ability of F. tularensis to prolong neutrophil lifespan. In addition, we discuss distinctive features of the bacterium, including its ability to act at a distance to alter overall neutrophil responsiveness to exogenous stimuli, and the evidence which suggests that macrophages and neutrophils play distinct roles in tularemia pathogenesis, such that macrophages are major vehicles for intracellular growth and dissemination, whereas neutrophils drive tissue destruction by dysregulation of the inflammatory response.
Molecular mechanisms regulating secretory organelles and endosomes in neutrophils and their implications for inflammation
Authors: Ramadass Mahalakshmi , Catz Sergio D 
Published: August 2016

SummaryNeutrophils constitute the first line of cellular defense against invading microorganisms and modulate the subsequent innate and adaptive immune responses. In order to execute a rapid and precise response to infections, neutrophils rely on preformed effector molecules stored in a variety of intracellular granules. Neutrophil granules contain microbicidal factors, the membrane‐bound components of the respiratory burst oxidase, membrane‐bound adhesion molecules, and receptors that facilitate the execution of all neutrophil functions including adhesion, transmigration, phagocytosis, degranulation, and neutrophil extracellular trap formation. The rapid mobilization of intracellular organelles is regulated by vesicular trafficking mechanisms controlled by effector molecules that include small GTPases and their interacting proteins. In this review, we focus on recent discoveries of mechanistic processes that are at center stage of the regulation of neutrophil function, highlighting the discrete and selective pathways controlled by trafficking modulators. In particular, we describe novel pathways controlled by the Rab27a effectors JFC1 and Munc13‐4 in the regulation of degranulation, reactive oxygen species and neutrophil extracellular trap production, and endolysosomal signaling. Finally, we discuss the importance of understanding these molecular mechanisms in order to design novel approaches to modulate neutrophil‐mediated inflammatory processes in a targeted fashion.
Tyrosine kinase signaling pathways in neutrophils
Authors: Futosi Krisztina , Mócsai Attila 
Published: August 2016

SummaryNeutrophils play a critical role in antimicrobial host defense, but their improper activation also contributes to inflammation‐induced tissue damage. Therefore, understanding neutrophil biology is important for the understanding, diagnosis, and therapy of both infectious and inflammatory diseases. Neutrophils express a large number of cell‐surface receptors that sense extracellular cues and trigger various functional responses through complex intracellular signaling pathways. During the last several years, we and others have shown that tyrosine kinases play a critical role in those processes. In particular, Src‐family and Syk tyrosine kinases couple Fc‐receptors and adhesion receptors (integrins and selectins) to various neutrophil effector functions. This pathway shows surprising similarity to lymphocyte antigen receptor signaling and involves various other enzymes (e.g. PLCγ2), exchange factors (e.g. Vav‐family members) and adapter proteins (such as ITAM‐containing adapters, SLP‐76, and CARD9). Those mediators trigger various antimicrobial functions and play a critical role in coordinating the inflammatory response through the release of inflammatory mediators, such as chemokines and LTB4. Interestingly, however, tyrosine kinases have a limited direct role in the migration of neutrophils to the site of inflammation. Here, we review the role of tyrosine kinase signaling pathways in neutrophils and how those pathways contribute to neutrophil activation in health and disease.
Neutrophils and the inflammatory tissue microenvironment in the mucosa
Authors: Campbell Eric L. , Kao Daniel J. , Colgan Sean P. 
Published: August 2016

SummaryThe interaction of neutrophils (PMNs) and epithelial cells are requisite lines of communication during mucosal inflammatory responses. Consequences of such interactions often determine endpoint organ function, and for this reason, much interest has developed around defining the constituents of the tissue microenvironment of inflammatory lesions. Physiologic in vitro and in vivo models have aided in the discovery of components that define the basic inflammatory machinery that mold the inflammatory tissue microenvironment. Here, we will review the recent literature related to the contribution of PMNs to molding of the tissue microenvironment, with an emphasis on the gastrointestinal (GI) tract. We focus on endogenous pathways for promoting tissue homeostasis and the molecular determinants of neutrophil–epithelial cell interactions during ongoing inflammation. These recent studies highlight the dynamic nature of these pathways and lend insight into the complexity of treating mucosal inflammation.
The European Parliament's Diplomacy – a Tool for Projecting EU Power in Times of Crisis? The Case of the Cox–Kwasniewski Mission
Authors: Nitoiu Cristian , Sus Monika 
Published: August 2016

AbstractThe aim of this paper is to shed light on the way the European Parliament's diplomacy affects EU power, particularly during times of crisis. The analysis is focused on the Cox–Kwasniewski mission that the Parliament sent to Ukraine in 2012–13. Based on interviews and existing literature, we discuss the genesis and the development of the mission and then evaluate its impact. We argue that the mission with time became a key diplomatic instrument and enabled EU power projection by giving momentum to the promotion of the EU's approach towards Ukraine, which was already wavering due to the deadlock over the Association Agreement between Kyiv and Brussels and then due to President Yanukovych's refusal to sign the agreement.
Effect of Kineret® on ovarian ischemia reperfusion injury in a rat model
Authors: Nayki Umit Arslan , Nayki Cenk , Cetin Nihal , Cimen Ferda Keskin , Coban Abdulkadir , Mammadov Renad , Tas Ismail Hakkı , Malkoc Ismail 
Published: August 2016

AbstractAimTo investigate the effect of Kineret® on ischemia reperfusion (IR) injury in rat ovaries.MethodsRats were divided into four groups: ovarian IR (IRG); 50 mg/kg Kineret® + ovarian IR (KIR‐50); 100 mg/kg Kineret® + ovarian IR (KIR‐100); and sham operation (SOC). KIR‐50 (n = 10) and KIR‐100 (n = 10) groups received an intraperitoneal injection of Kineret® at doses of 50 and 100 mg/kg, respectively. IRG and SOC (n = 10) rat groups were given distilled water as solvent using the same method. The results were compared between the groups.ResultsIn rats in which IR occurred, oxidant parameters, such as malondialdehyde (MDA) and myeloperoxidase (MPO), were increased, the level of proinflammatory interleukin 1 beta (IL‐1β) was elevated and total glutathione (tGSH) as an antioxidant was decreased in the ovarian tissues. Administration of Kineret® at a dose of 100 mg/kg inhibited the increase of MDA, MOP and IL‐1β and a decrease in tGSH caused by IR more significantly than administration of Kineret® at a dose of 50 mg/kg. In addition, 100 mg/kg Kineret® significantly decreased severe hemorrhage, degeneration and inflammatory signs in the follicular cells, caused by IR. Kineret® at 100 mg/kg markedly ameliorated increased apoptosis in ovarian tissue with IR more significantly than 50 mg/kg kineret.ConclusionOur findings indicate that Kineret® might be useful in clinical practice for the treatment of damage that may occur as a result of ovarian torsion.
Perinatal outcome of monochorionic diamniotic twin pregnancies complicated with isolated amniotic fluid volume abnormality of one twin less than 26 weeks of gestation
Authors: Kawamura Hiroshi , Ishii Keisuke , Mabuchi Aki , Yamamoto Ryo , Hayashi Shusaku , Mitsuda Nobuaki 
Published: August 2016

AbstractAimTo evaluate the incidence of twin‐twin transfusion syndrome (TTTS) and the perinatal outcome at 28 days of age in monochorionic diamniotic (MCDA) pregnancies complicated with isolated polyhydramnios (I‐Poly) and isolated oligohydramnios (I‐Oligo) diagnosed < 26 weeks of gestation.MethodsThis was a retrospective study of women with MCDA pregnancies diagnosed with I‐Poly or I‐Oligo before 26 weeks of gestation over a period of six years. The incidence of subsequent TTTS and neonatal outcome in terms of intact survival (IS) at 28 days of age were evaluated. Intact survival was defined as being alive without any neurological complications at 28 days of age.ResultsThere were 30 cases of I‐Poly and 53 of I‐Oligo that were eligible as per the inclusion criteria. Subsequent TTTS were complicated in six (20.0%) of the I‐Poly and 26 (49.0%) of the I‐Oligo cases. Among subjects with I‐Poly, 17 had spontaneously normalized amniotic fluid volume. Prolonged oligohydramnios until intrauterine death, delivery or the onset of emerging TTTS was noted in 16 cases of I‐Oligo. Both the twins exhibited IS in 26 (86.7%) cases of I‐Poly and 31 (58.4%) cases of I‐Oligo.ConclusionOne‐fifth of I‐Poly and half of I‐Oligo MCDA twins at < 26 weeks of gestation potentially develop TTTS. I‐Oligo in particular should be regarded as a high‐risk condition as neonatal IS is less than 60%.
Antineutrophil antibodies define clinical and genetic subgroups in primary sclerosing cholangitis
Authors: Hov Johannes R. , Boberg Kirsten M. , Taraldsrud Eli , Vesterhus Mette , Boyadzhieva Maria , Solberg Inger Camilla , Schrumpf Erik , Vatn Morten H. , Lie Benedicte A. , Molberg Øyvind , Karlsen Tom H. 
Published: August 2016

AbstractBackground & AimsThe strongest genetic risk factors in primary sclerosing cholangitis (PSC) are encoded in the HLA complex. Antineutrophil cytoplasmic antibodies (ANCA) have been reported in up to 94% of PSC patients, but their clinical significance and immunogenetic basis are ill defined. We aimed to characterize clinical and genetic associations of ANCA in PSC.MethodsAntineutrophil cytoplasmic antibodies were analysed with indirect immunofluorescence in 241 Norwegian PSC patients. HLA‐B and HLA‐DRB1 genotyping was performed in the patients and in 368 healthy controls. Data on perinuclear ANCA (pANCA) and HLA‐DRB1 were available from 274 ulcerative colitis (UC) patients without known liver disease.ResultsAntineutrophil cytoplasmic antibodies were found in 193 (80%) of the PSC patients, with pANCA in 169 (70%). ANCA‐positive patients were younger than ANCA negative at diagnosis of PSC and had a lower frequency of biliary cancer (9% vs 19%, P=.047). There were no differences between PSC patients with and without inflammatory bowel disease. Genetically, the strong PSC risk factors HLA‐B*08 (frequency in healthy 13%) and DRB1*03 (14%) were more prevalent in ANCA‐positive than ‐negative patients (43% vs 25%, P=.0012 and 43% vs 25%, P=.0015 respectively). The results were similar when restricting the analysis to pANCA‐positive patients. In UC patients without liver disease, HLA‐DRB1*03 was more prevalent in pANCA‐positive compared with ‐negative patients (P=.03).ConclusionsAntineutrophil cytoplasmic antibodies identified PSC patients with particular clinical and genetic characteristics, suggesting that ANCA may mark a clinically relevant pathogenetic subgroup in the PSC‐UC disease spectrum.
Differentially regulated high‐affinity iron assimilation systems support growth of the various cell types in the dimorphic pathogen Talaromyces marneffei
Authors: Pasricha Shivani , Schafferer Lukas , Lindner Herbert , Joanne Boyce Kylie , Haas Hubertus , Andrianopoulos Alex 
Published: August 2016

SummaryIron is a key trace element important for many biochemical processes and its availability varies with the environment. For human pathogenic fungi iron acquisition can be particularly problematical because host cells sequester free iron as part of the acute‐phase response to infection. Fungi rely on high‐affinity iron uptake systems, such as reductive iron assimilation (RIA) and siderophore‐mediated iron uptake (non‐RIA). These have been extensively studied in pathogenic fungi that exist outside of host cells, but much less is known for intracellular fungal pathogens. Talaromyces marneffei is a dimorphic fungal pathogen endemic to Southeast Asia. In the host T. marneffei resides within macrophages where it grows as a fission yeast. T. marneffei has genes of both iron assimilation systems as well as a paralogue of the siderophore biosynthetic gene sidA, designated sidX. Unlike other fungi, deletion of sidA or sidX resulted in cell type‐specific effects. Mutant analysis showed that T. marneffei yeast cells also employ RIA for iron acquisition, providing an additional system in this cell type that differs substantially from hyphal cells. These data illustrate the specialized iron acquisition systems used by the different cell types of a dimorphic fungal pathogen and highlight the complexity in siderophore‐biosynthetic pathways amongst fungi.