bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neutralizing Anti-IL-10 Antibody Blocks the Protective Effect of Tapeworm Infection in a Murine Model of Chemically Induced Colitis
Authors: Hunter Meaghan M. , Wang Arthur , Hirota Christina L. , McKay Derek M. 
Published: April 2014

Abstract
There is increasing evidence that parasitic helminth infection has the ability to ameliorate other disease conditions. In this study the ability of the rat tapeworm, Hymenolepis diminuta, to modulate dinitrobenzene sulfonic acid (DNBS)-induced colitis in mice is assessed. Mice receiving DNBS (3 mg intrarectally) developed colitis by 72 h after treatment. Mice infected 8 days before DNBS with five H. diminuta larvae were significantly protected from the colitis, as gauged by reduced clinical disease, histological damage scores, and myeloperoxidase levels. This anticolitic effect was dependent on a viable infection and helminth rejection, because no benefit was observed in mice given killed larvae or in infected STAT6 knockout mice or rats, neither of which eliminate H. diminuta. The anticolitic effect of H. diminuta was associated with increased colonic IL-10 mRNA and stimulated splenocytes from H. diminuta- plus DNBS-treated mice produced more IL-10 than splenocytes from DNBS-only treated mice. Coadministration of an anti-IL-10 Ab blocked the anticolitic effect of prophylactic H. diminuta infection. Also, mice infected 48 h after DNBS treatment showed an enhanced recovery response. Finally, using a model of OVA hypersensitivity, we found no evidence of concomitant H. diminuta infection enhancing enteric responsiveness to subsequent ex vivo OVA challenge. The data show that a viable infection of H. diminuta in a nonpermissive system exerts a profound anticolitic effect (both prophylactically and as a treatment) that is mediated at least in part via IL-10 and does not predispose to enhanced sensitivity to bystander proteins.
Probiotics Ameliorate Recurrent Th1-Mediated Murine Colitis by Inducing IL-10 and IL-10-Dependent TGF-β-Bearing Regulatory Cells
Authors: Di Giacinto Claudia , Marinaro Mariarosaria , Sanchez Massimo , Strober Warren , Boirivant Monica 
Published: April 2014

Abstract
Recent studies of murine models of mucosal inflammation suggest that, whereas some kinds of bacterial microflora are inducers of disease, others, known as probiotics, prevent disease. In the present study, we analyzed the regulatory cytokine and cell response to probiotic (VSL#3) administration in the context of the Th1 T cell colitis induced by trinitrobenzene sulfonic acid treatment of SJL/J mice. Daily administration of probiotics for 3 wk to mice during a remission period between a first and second course of colitis induced by trinitrobenzene sulfonic acid, resulted in a milder form of recurrent colitis than observed in mice administered PBS during this same period. This protective effect was attributable to effects on the lamina propria mononuclear cell (LPMC) population, because it could be transferred by LPMC from probiotic-treated mice to naive mice. Probiotic administration was associated with an early increase in the production of IL-10 and an increased number of regulatory CD4+ T cells bearing surface TGF-β in the form of latency-associated protein (LAP) (LAP+ T cells). The latter were dependent on the IL-10 production because administration of anti-IL-10R mAb blocked their appearance. Finally, the LAP+ T cells were essential to the protective effect of probiotics because administration of anti-IL-10R or anti-TGF-β at the initiation of recurrent colitis induction or depletion of LAP+ T cells from LPMC abolished the latter’s capacity to transfer protection to naive recipients. These studies show that probiotic (VSL#3) administration during a remission period ameliorates the severity of recurrent colitis by inducing an immunoregulatory response involving TGF-β-bearing regulatory cells.
Neisserial Porin-Induced Dendritic Cell Activation Is MyD88 and TLR2 Dependent
Authors: Singleton Theresa E. , Massari Paola , Wetzler Lee M. 
Published: April 2014

Abstract
Neisserial porins have been shown to act as B cell mitogens and immune adjuvants. PorA and PorB are the major outer membrane porin proteins of the human pathogen Neisseria meningitidis. We have shown that the mechanism of the immunopotentiating capability of porin involves up-regulation of the T cell costimulatory ligand, CD86. Due to neisserial porin’s ability to activate B cells and potentiate immune responses, we hypothesized that porin also employs the potent immune stimulatory function of dendritic cells (DC). We examined the ability of purified N. meningitidis PorB to induce maturation of murine splenic and bone marrow-derived DC. PorB treatment induced DC maturation, as demonstrated by increased expression of CD86 and class I and II MHC molecules. In addition, PorB not only enhanced the allostimulatory activity of DC, but also augmented the ability of DC to stimulate T cells in an Ag-specific manner. PorB-matured DC secreted the inflammatory cytokine IL-6, which may have implications for the adjuvant property of porin. Induction of IL-6 by PorB is also significant because IL-6 is one of a number of cytokines produced during infection with N. meningitidis and may be involved in the inflammatory process observed during infection and disease. We previously demonstrated the requirement of MyD88 and TLR2 for PorB-induced B cell activation. In the present study, MyD88 and TLR2 were also essential for PorB-induced DC activation. This work is significant for elucidating the mechanism(s) of neisserial porin’s immune stimulatory activity.
IL-22 Inhibits Epidermal Differentiation and Induces Proinflammatory Gene Expression and Migration of Human Keratinocytes
Authors: Boniface Katia , Bernard François-Xavier , Garcia Martine , Gurney Austin L. , Lecron Jean-Claude , Morel Franck 
Published: April 2014

Abstract
IL-22 belongs to a family of cytokines structurally related to IL-10, including IL-19, IL-20, IL-24, and IL-26. In contrast to IL-10, IL-22 has proinflammatory activities. IL-22 signals through a class II cytokine receptor composed of an IL-22-binding chain, IL-22RA1, and the IL-10RB subunit, which is shared with the IL-10R. In the present study, we show that short-term cultured human epidermal keratinocytes express a functional IL-22R but no IL-10R. Accordingly, IL-22 but not IL-10 induces STAT3 activation in keratinocytes. Using a cDNA array screening approach, real-time RT-PCR, and Western blot analysis, we demonstrate that IL-22 up-regulates, in a dose-dependent manner, the expression of S100A7, S100A8, S100A9, a group of proinflammatory molecules belonging to the S100 family of calcium-binding proteins, as well as the matrix metalloproteinase 3, the platelet-derived growth factor A, and the CXCL5 chemokine. In addition, IL-22 induces keratinocyte migration in an in vitro injury model and down-regulates the expression of at least seven genes associated with keratinocyte differentiation. Finally, we show that IL-22 strongly induces hyperplasia of reconstituted human epidermis. Taken together, these results suggest that IL-22 plays an important role in skin inflammatory processes and wound healing.
Activation of the Prostaglandin D2 Receptor DP2/CRTH2 Increases Allergic Inflammation in Mouse
Authors: Spik Isabelle , Brénuchon Céline , Angéli Véronique , Staumont Delphine , Fleury Sébastien , Capron Monique , Trottein François , Dombrowicz David 
Published: April 2014

AbstractAllergic pathologies are often associated with IgE production, mast cell activation, and eosinophilia. PGD2 is the major eicosanoid, among several inflammatory mediators, released by mast cells. PGD2 binds to two membrane receptors, D prostanoid receptor (DP)1 and DP2, endowed with antagonistic properties. In humans, DP2 is preferentially expressed on type 2 lymphocytes, eosinophils, and basophils and mediates chemotaxis in vitro. Although not yet supported by in vivo studies, DP2 is thought to be important in the promotion of Th2-related inflammation. Herein, we demonstrate that mouse eosinophils express both DP1 and DP2 and that PGD2 exerts in vitro chemotactic effects on eosinophils through DP2 activation. Furthermore, 13,14-dihydro-15-keto-PGD2, a specific DP2 agonist not only increases eosinophil recruitment at inflammatory sites but also the pathology in two in vivo models of allergic inflammation: atopic dermatitis and allergic asthma. By contrast, DP1 activation tends to ameliorate the pathology in asthma. Taken together, these results support the hypothesis that DP2 might play a critical role in allergic diseases and underline the interest of DP2 antagonists in human therapy.
Unconjugated Bilirubin Inhibits VCAM-1-Mediated Transendothelial Leukocyte Migration
Authors: Keshavan Pavitra , Deem Tracy L. , Schwemberger Sandy J. , Babcock George F. , Cook-Mills Joan M. , Zucker Stephen D. 
Published: April 2014

Abstract
During lymphocyte migration, engagement of VCAM-1 stimulates the generation of endothelial cell-derived reactive oxygen species (ROS) and activation of matrix metalloproteinases, facilitating endothelial retraction. Because bilirubin is a potent antioxidant, we examined the hypothesis that this bile pigment inhibits VCAM-1-dependent cellular events. The migration of isolated murine splenic lymphocytes across monolayers of murine endothelial cell lines (which constitutively express VCAM-1) is significantly inhibited by physiological concentrations of bilirubin, in the absence of an effect on lymphocyte adhesion. Bilirubin administration also suppresses VCAM-1-stimulated ROS generation and reduces endothelial cell matrix metalloproteinase activity. In a murine asthma model characterized by VCAM-1-dependent airway inflammation, treatment of C57BL6/J mice with i.p. bilirubin decreases the total leukocyte count in the lung parenchyma and lavage fluid, through specific inhibition of eosinophil and lymphocyte infiltration. Blood eosinophil counts were increased in bilirubin-treated animals, while VCAM-1 expression in the capillary endothelium and cytokine levels in both lung lavage and supernatants from cultured lymph node lymphocytes were unchanged, suggesting that bilirubin inhibits leukocyte migration. Conclusion: bilirubin blocks VCAM-1-dependent lymphocyte migration in vitro and ameliorates VCAM-1-mediated airway inflammation in vivo, apparently through the suppression of cellular ROS production. These findings support a potential role for bilirubin as an endogenous immunomodulatory agent.
Prolonged Lymphopenia, Lymphoid Depletion, and Hypoprolactinemia in Children with Nosocomial Sepsis and Multiple Organ Failure
Authors: Felmet Kate A. , Hall Mark W. , Clark Robert S. B. , Jaffe Ronald , Carcillo Joseph A. 
Published: April 2014

AbstractLymphopenia and lymphoid depletion occur in adults dying of sepsis. Prolactin increases Bcl-2 expression, suppresses stress-induced lymphocyte apoptosis, and improves survival from experimental sepsis. We hypothesized that prolonged lymphopenia, lymphoid depletion, and hypoprolactinemia occur in children dying with sepsis and multiple organ failure (MOF). Fifty-eight critically ill children with and 55 without MOF admitted to a university hospital pediatric intensive care unit were enrolled in a prospective, longitudinal, observational clinical study. Prolactin levels and absolute lymphocyte count were measured on days 1, 3, 7, 14, and 21. Lymph node, thymus, and spleen autopsy specimens were examined for lymphoid depletion, with immunohistochemical staining for CD4, CD20, and CD21 and for lymphoid apoptosis. Prolonged lymphopenia (absolute lymphocyte count &lt; 1000 for &gt;7 days) occurred only in children with MOF (29 vs 0%, p &lt; 0.05) and was associated independently with nosocomial infection (odds ratio (OR), 5.5, 95% confidence interval (CI), 1.7–17, p &lt; 0.05), death (OR, 6.8, 95% CI, 1.3–34, p &lt; 0.05), and splenic and lymph node hypocellularity (OR, 42, 95% CI, 3.7–473, p &lt; 0.05). Lymphocyte apoptosis and ante/postmortem infection were observed only in children with lymphoid depletion. Prolonged hypoprolactinemia (&gt;7 days) was more common in children with MOF (17 vs 2%, p &lt; 0.05) and was associated independently with prolonged lymphopenia (OR, 8.3, 95% CI, 2.1–33, p &lt; 0.05) and lymphoid depletion (OR, 12.2, 95% CI, 2.2–65, p &lt; 0.05). Prolonged lymphopenia and apoptosis-associated depletion of lymphoid organs play a role in nosocomial sepsis-related death in critically ill children. Prolonged hypoprolactinemia is a previously unrecognized risk factor for this syndrome.
Signal-Specific Activation and Regulation of Human Neutrophil Fcγ Receptors
Authors: Nagarajan Shanmugam , Fifadara Nimita H. , Selvaraj Periasamy 
Published: April 2014

Abstract
FcγRs with the ITIM domain have been shown to regulate the inflammatory signal delivered by the ITAM-containing FcγRs. In this study, we demonstrate that the function of human neutrophil FcγR type IIA (CD32A) is regulated in a distinct manner by different cell activation signals at the ligand-binding stage. Activation of neutrophils with fMLP up-regulated the ligand-binding function of CD32A, whereas PMA-mediated activation completely abolished ligand binding without altering CD32A expression. Furthermore, PMA treatment also abolished CD16B-dependent ligand binding irrespective of the level of expression. The effect of PMA was cell type specific, because the ligand-binding function of CD32A expressed on cultured cells such as K562 and CHO-CD32A transfectants was not affected by PMA. Interestingly, phorbol 12,13-dibutyrate, another phorbol ester, and IL-8 up-regulated CD32A-dependent ligand-binding function. These results demonstrate that regulation of CD32A-dependent ligand binding in human neutrophils is not only cell type specific but also activation signal specific. Moreover, these results suggest the possibility that signals delivered to neutrophils by various inflammatory stimuli can exert opposing effects on the function of human FcγRs, representing a novel inside-out regulatory mechanism of FcγR ligand binding.
A Role for CD103 in the Retention of CD4+CD25+ Treg and Control of Leishmania major Infection
Authors: Suffia Isabelle , Reckling Stacie K. , Salay Gerson , Belkaid Yasmine 
Published: April 2014

Abstract
Endogenous regulatory T cells (Treg) play a central role in the control of excessive or misdirected immune responses against self or foreign Ags. To date, virtually no data are available on the nature of the molecules and signals involved in the trafficking and retention of Treg in tissues where regulation is required. Here, we show that expression of αEβ7 integrin is necessary for the homing of Treg at site of Leishmania major infection. The vast majority of Treg present in the dermis at steady-state conditions or during L. major infection express the αE chain (CD103) of αEβ7. Genetically susceptible BALB/c mice that lack CD103 become resistant to infection, a phenotype that is associated with a poor capacity of Treg to be retained in the infected site. Such susceptible phenotype can be restored when Treg from wild-type mice were transferred in CD103−/− mice. The central role of CD103 in Treg retention was further demonstrated by usage of blocking Abs against CD103 and the transfer of Treg purified from CD103−/− mice. Our results strongly suggest that this molecule is induced and maintained on Treg following or just prior to their arrival in tissues. Furthermore, the expression of CD103 and the subsequent retention of Treg in tissues is highly regulated by their exposure to Leishmania Ag and the level of activation of the APCs they encounter. Thus, CD103, by controlling Treg retention, can contribute to the outcome of chronic infection by Leishmania.
Granzyme B Binds to Target Cells Mostly by Charge and Must Be Added at the Same Time as Perforin to Trigger Apoptosis
Authors: Shi Lianfa , Keefe Dennis , Durand Enrique , Feng Hanping , Zhang Dong , Lieberman Judy 
Published: April 2014

Abstract
Perforin (PFN) delivery of granzymes (Gzm) into the target cell at the immunological synapse is the major pathway for inducing apoptosis of virus-infected cells and tumors. A validated model for how PFN delivers Gzm into the cytosol is still lacking. PFN was originally thought to work by forming pores in the target cell plasma membrane that allow Gzm entry. This model was questioned when it was shown that GzmB is endocytosed without PFN. Moreover, apoptosis could be triggered by adding PFN to washed cells that have previously endocytosed GzmB. In this study, we show that GzmB binds to the plasma membrane mostly via nonspecific charge interactions. Washing in saline does not remove bound Gzm. However, if externally bound GzmB is completely removed, subsequent addition of PFN does not release previously endocytosed GzmB and does not trigger apoptosis. Therefore, PFN must be coendocytosed with GzmB to deliver it into the cytosol.
Insulin-Like Growth Factor-1 Controls Type 2 T Cell-Independent B Cell Response
Authors: Baudler Stephanie , Baumgartl Julia , Hampel Brigitte , Buch Thorsten , Waisman Ari , Snapper Clifford M. , Krone Wilhelm , Brüning Jens C. 
Published: April 2014

AbstractThe IGF-1 receptor (IGF-1R) is expressed on T and B lymphocytes, and the expression of the insulin- and IGF-1-signaling machinery undergoes defined changes throughout lineage differentiation, offering a putative role for IGF-1 in the regulation of immune responses. To study the role of the IGF-1R in lymphocyte differentiation and function in vivo, we have reconstituted immunodeficient RAG2-deficient mice with IGF-1R−/− fetal liver cells. Despite the absence of IGF-1Rs, the development and ex vivo activation of B and T lymphocytes were unaltered in these chimeric mice. By contrast, the humoral immune response to the T cell-independent type 2 Ag 4-hydroxy-3-nitrophenyl acetyl-Ficoll was significantly reduced in mice reconstituted with IGF-1R-deficient fetal liver cells, whereas responses to the T cell-dependent Ag 4-hydroxy-3-nitrophenyl acetyl-chicken globulin were normal. Moreover, in an in vitro model of T cell-independent type 2 responses, IGF-1 promoted Ig production potently upon polyvalent membrane-IgD cross-linking. These data indicate that functional IGF-1R signaling is required for T cell-independent B cell responses in vivo, defining a novel regulatory mechanism for the immune response against bacterial polysaccharides.
A Randomized Double Blind Controlled Safety Trial Evaluating D-Lactic Acid Production in Healthy Infants Fed a Lactobacillus reuteri-containing Formula
Authors: Papagaroufalis Konstantinos , Fotiou Aikaterini , Egli Delphine , Tran Liên-Anh , Steenhout Philippe 
Published: April 2014

Background D-Lactic acidosis in infants fed lactic acid bacteria-containing products is a concern. Methods The primary objective of this non-inferiority trial was to compare urinary D-lactic acid concentrations during the first 28 days of life in infants fed formula containing Lactobacillus reuteri (1.2 x 106 colony forming units (CFU)/ml) with those fed a control formula. The non-inferiority margin was set at a two-fold increase in D-lactic acid (0.7 mmol/mol creatinine, log-transformed). Healthy term infants in Greece were enrolled between birth and 72 hours of age, and block randomized to a probiotic ( N = 44) or control ( N = 44) group. They were exclusively fed their formulae until 28 days of age and followed up at 7, 14, 28, 112, and 168 ± 3 days. Anthropometric measurements were taken at each visit and tolerance recorded until 112 days. Urine was collected before study formula intake and at all visits up to 112 days and blood at 14 days. Results D-Lactic acid concentration in the probiotic group was below the non-inferiority margin at 28 days: treatment effect -0.03 (95% confidence interval [CI]: [-0.48 to 0.41]) mmol/mol creatinine but was above the non-inferiority margin at 7 and 14 days–-treatment effect 0.50 (95% CI: [0.05-0.96]) mmol/mol creatinine and 0.45 (95% CI: [0.00-0.90]) mmol/mol creatinine, respectively. Blood acid excess and pH, anthropometry, tolerance, and adverse events (AEs) were not significantly different between groups. Conclusion Intake of L. reuteri-containing formula was safe and did not cause an increase in D-lactic acid beyond two weeks. Trial Registration ClinicalTrials.gov NCT01119170.
Distance Caregivers of People with Alzheimer's Disease and Related Dementia: A Phenomenological Study
Authors: Edwards Megan 
Published: April 2014

Introduction: This research study focused on exploring the lived experience of people caring for someone with Alzheimer's disease and related dementia from a distance (defined as 2 or more hours' distance by car) to help shed light on this caregiving population. Method: Ten participants (all adult children caring for a parent with Alzheimer's disease and related dementia) were involved in this qualitative, phenomenological study. Each participant took part in two individual interviews, the first interview in person with a follow-up interview by telephone phone. After the interviews were transcribed, data were analysed using Moustakas's (1994) modified Van Kaam Method. Findings: Six general themes were derived from quotations from participants, revealing different aspects of the distance caregiving experience. Findings indicated that participants spent much time managing and coordinating the care of their relative. Participants indicated a wish to provide information on their relative that could help healthcare professionals provide effective care, and felt that the process of providing care to their relative impacted their professional and personal lives, including developing deeper connections with their relative and others. According to participants, the experience of caregiving, and balancing caregiving demands with other life demands, led to personal changes and growth. Conclusion: Occupational therapists and other healthcare professionals need to interact and communicate with distance caregivers of people with Alzheimer's disease and related dementia to better support the caregivers and the care being provided to the person with dementia.
Master's Level Occupational Therapy Students on Placement: An Exploration of Perceptions and Expectations
Authors: Bell Janice , Cox Diane , Marcangelo Caroline 
Published: April 2014

Introduction: The aims of this exploratory mixed methods study were to explore practice placement educators' perceptions and expectations of pre-registration master's level students on placement and to compare the findings of educators who had previous experience of master's level students with those who had none. Method: Twenty-six educators completed questionnaires and four took part in semi-structured interviews; forty placement reports were reviewed. Findings: The findings show that many educators have higher expectations of master's level students than they do of undergraduate students, due to perceptions of maturity and previous education, life, and work experience. These expectations were contradicted, however, by concerns that master's level students achieve less academic and clinical competence in the shorter time frame for study. Staff with no prior experience at this level lacked confidence in their own abilities to meet the challenge of supporting a master's level student, while staff experienced at this level found many benefits for their own learning as well as for their clinical team. Conclusion: Further education, support, and collaboration with the university could enhance the placement experience for both educators and students and may result in the acquisition of more placement offers. The findings will be used to inform future educator training days as well as widen dissemination of information to all practice placement educators. Further collaboration and effective communication between the university and the educators may promote self-confidence in staff, enhance confidence in student abilities, as well as ensuring that assessment is provided at an appropriate level.