bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sphingolipids – roads still to be taken
Authors: Schengrund C. L. 
Published: July 2010

Despite advances already made towards understanding the biological role(s) of sphingolipids (SLs) there are still a number of questions that need to be addressed.For example, while glycosphingolipids (GSLs) are known to be a component of lipid rafts, where they can provide multivalent ligands for carbohydrate–carbohydrate interactions, their actual function in the rafts is unknown. When gangliosides are added to cells and associate with their plasma membranes are they found in rafts or do they distribute in a relatively even fashion across the entire cell membrane? What happens to raft formation in cells made GSL minus? How do subtle changes in a cell's total SL composition, or in the ceramide or polar portion of a specific SL, affect its behavior? What are the specific functions of the different carbohydrate moieties associated with GSLs? In addition to their known role as ligands for certain pathogens, do they function as specific ligands for endogenous molecules? How does substitution of a deoxy for a hydroxyl group on a sugar molecule in a GSL affect their function? Does replacement of a ganglioside sialic acid with a different, negatively charged, component (e.g. sulfate) alter its behavior? How are GSLs transported from the site of injection to their putative site of action when used in animal or human trials to enhance neuronal recovery? Do they associate with albumin? Are they cleared from the circulation by specific galactose binding proteins? Can their clearance by the liver be reduced by modifying their carbohydrate portion? Each of the above questions describes a road currently in need of more exploration.
Agonists specific for the transcription factor PPARdelta accelerate differentiation of oligodendrocytes
Authors: Skoff R. P. , Bessert D. , Saluja I. , Granneman J. 
Published: July 2010

Peroxisome proliferator activated receptors (PPARs) are transcription factors belonging to the nuclear hormone receptor superfamily that regulate key genes involved in lipid metabolism. PPARδ is ubiquitously expressed at low levels in many tissues and its function has remained elusive. However, we have shown that PPARδ is abundantly expressed in oligodendrocytes (Ols), suggesting this receptor plays a critical role in oligodendrocyte differentiation (Granneman et al. 1998 J. Neurosci. Res51, 563). We first investigated the effects of PPAR agonists on proliferation and differentiation of Ols in tissue culture. Primary glial and enriched Ol cultures were treated with ligands that specifically activate PPARγ and PPARδ (Berger et al. 1999 J. Biol. Chem. 274, 6717). PPARδ but not PPARγ agonists increased the size of OL membrane sheets within 24 h of application. The increase in membrane sheet size was mirrored by increases in MBP and PLP mRNA's. In enriched Ol cultures, the number of Ols was increased 70% with the PPARδ agonist but not the PPARγ agonist (Saluja et al. 2001 Glia33, 191). In vivo injections of PPARδ agonist into P2 and P3 mice show an increase of total macroglia in the ventral and dorsal funiculi of the spinal cord of 20–40% compared to controls. Preliminary observations suggest the Ols in agonist treated cultures are larger and more densely stained than controls. Our results show for the first time that a specific ligand for a transcription factor is capable of activating the program of Ol differentiation.Acknowledgements: Supported by NMSS.
Antibiotic‐associated Bloody Diarrhea in Infants: Clinical, Endoscopic, and Histopathologic Profiles
Authors: Barakat Maha , El‐Kady Zeinab , Mostafa Mohamed , Ibrahim Naglaa , Ghazaly Hamdy 
Published: July 2010

ABSTRACTObjective:Antibiotic‐associated diarrhea constitutes 1 of the most frequent side effects of antimicrobial therapy with widely varying clinical presentations; however, little is known about its antibiotic‐associated bloody diarrhea (AABD) form, particularly in very young children. The aim of this study was to describe the clinical, endoscopic, and histopathologic profiles of community‐acquired AABD in infants.Patients and Methods:The study included 23 infants referred with bloody diarrhea that developed a few days after receiving antibiotics on an outpatient basis for watery diarrhea (18), respiratory tract infections (4), or urinary tract infection (1). Detailed clinical assessment, videosigmoidoscopy, and histopathologic examination of endoscopic biopsies were performed for all.Results:Clinically, on presentation, bloody diarrhea was acute in all except 1 patient with a prolonged course (for 25 days) and stopped in all 2 to 6 days after discontinuation of antibiotics. Fever and/or leukocytosis were present only in 8 (34.8%). Sigmoidoscopy revealed varying types of erythema (patchy, ring, diffuse) and ulcers (aphthoid, diffuse) in 18 and pseudomembranes in 5. Histopathologically, only 3 showed the characteristic mushroom‐like pseudomembranes, whereas all of the other infants had nonspecific colitis.Conclusions:Community‐acquired AABD is not uncommon in infants presenting with acute or chronic forms even without fever or leukocytosis. When suspected, discontinuation of antibiotics is a good policy if facilities for bacterial culture with cytotoxin assays are limited. The characteristic endoscopic or histopathologic pseudomembranes are encountered only in a small percentage (26%). Rational use of antibiotics should be adhered to particularly in cases of watery diarrhea that is mostly of viral origin.
Increased Number of Regulatory T Cells in Children With Eosinophilic Esophagitis
Authors: Fuentebella Judy , Patel Anup , Nguyen Tammie , Sanjanwala Bharati , Berquist William , Kerner John A , Bass Dorsey , Cox Kenneth , Hurwitz Melissa , Huang Jennifer , Nguyen Christine , Quiros J Antonio , Nadeau Kari 
Published: July 2010

ABSTRACTObjectives:There are limited data on the role of regulatory T cells (Treg) in the disease pathology of eosinophilic esophagitis (EoE). We tested the differences in Treg in subjects with EoE compared with those with gastroesophageal reflux disease (GERD) and healthy controls (HC).Patients and Methods:Pediatric patients evaluated by endoscopy were recruited for our study. Participants were categorized into 3 groups: EoE, GERD, and HC. RNA purified from esophageal biopsies were used for real‐time quantitative polymerase chain reaction assays and tested for forkhead box P3 (FoxP3) mRNA expression. Treg were identified as CD4+CD25hiCD127lo cells in peripheral blood and as CD3+/FoxP3+cells in esophageal tissue.Results:Forty‐eight subjects were analyzed by real‐time quantitative polymerase chain reaction: EoE (n = 33), GERD (n = 7), and HC (n = 8). FoxP3 expression was higher by up to 1.5‐fold in the EoE group compared with the GERD and HC groups (P < 0.05). Protein levels of FoxP3 in blood and tissue were then investigated in 21 subjects: EoE (n = 10), GERD (n = 6), and HC (n = 5). The percentage of Treg and their subsets in peripheral blood were not significant between groups (P > 0.05). The amount of Treg in esophageal tissue was significantly greater in the EoE group (mean 10.7 CD3+/FoxP3+cells/high power field [HPF]) compared with the other groups (GERD, mean 1.7 CD3+/FoxP3+cells/HPF and HC, mean 1.6 CD3+/FoxP3+cells/HPF) (P < 0.05).Conclusions:We show that Treg are increased in esophageal tissue of EoE subjects compared with GERD and HC subjects. The present study illustrates another possible mechanism involved in EoE that implicates impairment of immune homeostasis.
Increased HLA‐DR Expression on Tissue Eosinophils in Eosinophilic Esophagitis
Authors: Patel Anup J , Fuentebella Judy , Gernez Yael , Nguyen Tammie , Bass Dorsey , Berquist William , Cox Kenneth , Sibley Eric , Kerner John , Nadeau Kari 
Published: July 2010

ABSTRACTObjective:The aim of the study was to investigate whether eosinophils have increased human leukocyte antigen (HLA)‐DR expression in subjects with eosinophilic esophagitis (EoE) compared with controls.Patients and Methods:Patients who were undergoing an upper endoscopy with biopsies for suspected gastroesophageal reflux disease (GERD) or EoE at Lucile Packard Children's Hospital were enrolled. In total, the blood and tissue samples of 10 healthy controls (HC), 11 subjects with GERD, and 10 with EoE were studied. Multiple tissue staining to identify eosinophils (via eosinophil cationic protein‐clone EG2) and major histocompatibility complex class II cell surface receptors (via HLA‐DR) was performed via immunohistochemistry. The peripheral blood was analyzed using flow cytometry to detect eosinophil HLA‐DR expression among these subjects.Results:In the tissue, a greater proportion of eosinophils expressed HLA‐DR among the subjects with EoE (mean 0.83 ± 0.14, n = 9) relative to those with GERD (mean 0.18 ± 0.19, n = 8, P < 0.01) and HC (mean 0.18 ± 0.13, n = 6, P < 0.01). In total, 6 participants (4 HC subjects and 2 subjects with GERD) did not have any eosinophils identified on tissue staining and were unable to be included in the present statistical analysis. In the blood, there was no statistically significant difference in eosinophil HLA‐DR expression among HC subjects (mean 415 ± 217, n = 6), subjects with GERD (mean 507 ± 429, n = 2), and those with EoE (mean 334 ± 181, n = 6).Conclusions:These data demonstrate that the eosinophils from the esophagus of subjects with EoE have increased HLA‐DR expression within this tissue.
Role of Postnatal Acquisition of the Intestinal Microbiome in the Early Development of Immune Function
Authors: Dimmitt Reed A , Staley Elizabeth M , Chuang Gin , Tanner Scott M , Soltau Thomas D , Lorenz Robin G 
Published: July 2010

ABSTRACTObjectives:Therapy with broad‐spectrum antibiotics is a common practice for premature infants. This treatment can reduce the biodiversity of the fecal microbiota and may be a factor in the cause of necrotizing enterocolitis. In contrast, probiotic treatment of premature infants reduces the incidence of necrotizing enterocolitis. We hypothesized that 1 mechanism for these observations is the influence of bacteria on postnatal development of the mucosal immune system.Materials and Methods:Expression of immune molecules and microbial sensors was investigated in the postnatal mouse gastrointestinal tract by real‐time polymerase chain reaction. Subsequently, 2‐week‐old specific pathogen‐free and microbial‐reduced (MR; antibiotic treated) mice were compared for immune molecule and microbial sensor expression, mesenteric lymph node T‐cell numbers and activation, intestinal barrier function/permeability, systemic lymphocyte numbers, and T‐cell phenotype commitment.Results:Toll‐like receptor 2, 4, and 5 expression was highest in 2‐week‐old specific pathogen‐free mice, and this expression was decreased in MR mice. There was no difference in intestinal tight‐junctional function, as evaluated by fluorescein isothiocyanate‐dextran uptake, but MR mice had increased bacterial translocation across the intestinal epithelial barrier. MR mice had significantly fewer splenic B cells and mesenteric lymph node CD4+ T cells, but there were normal numbers of splenic T cells. These systemic T cells from MR mice produced more interleukin‐4 and less interferon‐γ and IL‐17, indicative of maintenance of the fetal, T‐helper cell type 2 phenotype.Conclusions:The present study shows that intestinal commensal microbiota have an influence on early postnatal immune development. Determining specific bacteria and/or bacterial ligands critical for this development could provide insight into the mechanisms by which broad‐spectrum antibiotics and/or probiotic therapy influence the development of the mucosal immune system and mucosal‐related diseases.
Munchausen Syndrome by Proxy: Ongoing Clinical Challenges
Authors: Squires Janet E , Squires Robert H 
Published: July 2010

ABSTRACTIn 1977, Roy Meadow, a pediatric nephrologist, first described a condition he subsequently coined Munchausen syndrome by proxy. The classic form involves a parent or other caregiver who inflicts injury or induces illness in a child, deceives the treating physician with fictitious or exaggerated information, and perpetrates the trickery for months or years. A related form of pathology is more insidious and more common but also damaging. It involves parents who fabricate or exaggerate symptoms of illness in children, causing overly aggressive medical evaluations and interventions. The common thread is that the treating physician plays a role in inflicting the abuse upon the child. Failure to recognize the problem is common because the condition is often not included in the differential diagnosis of challenging or confusing clinical problems. We believe that a heightened “self‐awareness” of the physician's role in Munchausen syndrome by proxy will prevent or reduce the morbidity and mortality associated with this diagnosis. In addition, we believe contemporary developments within the modern health care system likely facilitate this condition.
A Metabolomic Approach to Study Major Metabolite Changes during Acclimation to Limiting CO2 in Chlamydomonas reinhardtii
Authors: Renberg Linda , Johansson Annika I. , Shutova Tatiana , Stenlund Hans , Aksmann Anna , Raven John A. , Gardeström Per , Moritz Thomas , Samuelsson Göran 
Published: July 2010

Abstract
Using a gas chromatography-mass spectrometry-time of flight technique, we determined major metabolite changes during induction of the carbon-concentrating mechanism in the unicellular green alga Chlamydomonas reinhardtii. In total, 128 metabolites with significant differences between high- and low-CO2-grown cells were detected, of which 82 were wholly or partially identified, including amino acids, lipids, and carbohydrates. In a 24-h time course experiment, we show that the amino acids serine and phenylalanine increase transiently while aspartate and glutamate decrease after transfer to low CO2. The biggest differences were typically observed 3 h after transfer to low-CO2 conditions. Therefore, we made a careful metabolomic examination at the 3-h time point, comparing low-CO2 treatment to high-CO2 control. Five metabolites involved in photorespiration, 11 amino acids, and one lipid were increased, while six amino acids and, interestingly, 21 lipids were significantly lower. Our conclusion is that the metabolic pattern during early induction of the carbon-concentrating mechanism fit a model where photorespiration is increasing.
Review article: lymphatic system and associated adipose tissue in the development of inflammatory bowel disease
Authors: Von Der Weid P.‐Y. , Rainey K. J. 
Published: July 2010

SummaryBackground The lymphatic system plays critical roles in tissue fluid homoeostasis, immune defence and metabolic maintenance. Lymphatic vessels transport lymph, proteins, immune cells and digested lipids, allowing fluid and proteins to be returned to the blood stream, lipids to be stored and metabolized and antigens to be sampled in lymph nodes. Lymphatic drainage is mainly driven by rhythmic constrictions intrinsic to the vessels and critically modulated by fluid pressure and inflammatory mediators.Aim To collect and discuss the compelling available information linking the lymphatic system, adiposity and inflammation.Methods A literature search was performed through PubMed focusing on lymphatic system, inflammation, immune cells and fat transport and function in the context of IBD.Results Evidence collected allows us to propose the following working model. Compromised lymph drainage, reported in IBD, leads to oedema, lymphangiogenesis, impaired immune cell trafficking and lymph leakage. Lymph factor(s) stimulate adipose tissue to proliferate and produce cytokines, which affect immune cell functions and exacerbate inflammation.Conclusions Understanding the lymphatic system’s role in immune cell trafficking and immune responses, contribution to fat transport, distribution, metabolism and implication in the pathogenesis of chronic intestinal inflammation may provide the basis for new therapeutic strategies and improved quality‐of‐life.
Children with atopic histories exhibit impaired lipopolysaccharide‐induced Toll‐like receptor‐4 signalling in peripheral monocytes
Authors: Préfontaine D. , Banville‐Langelier A.‐A. , Fiset P.‐O. , Guay J. , An J. , Mazer M. , Hamid Q. , Mazer B. D. 
Published: July 2010

SummaryBackground
The hygiene hypothesis states that early exposure to bacterial products such as lipopolysaccharide (LPS) may be protective against the development of allergic diseases. Whether atopic disease affects the ability of immune cells to respond to LPS is unclear. Our laboratory has demonstrated previously that children express high levels of Toll‐like receptor (TLR)‐4 on CD4+ cells in nasal mucosa.Objective
To determine if children with a history of allergic disease have impaired responses to LPS on circulating CD4+ leucocytes.Methods
Peripheral blood mononuclear cells from children (aged 2–18) and adults with or without a history of atopic conditions were cultured with/without IL‐4 or LPS for up to 24 h. Expression of surface TLR‐4, CD14, CD4, CD3, as well as of intracellular phosphorylated p42/p44ERK and p38 mitogen‐activated protein kinase (MAPK) were assessed by flow cytometry.Results
A history of atopy in children was associated with impaired LPS‐induced TLR‐4‐dependent phosphorylation of p42/44ERK and p38 MAPK by CD4+ monocytes. Decreased LPS signalling was reproduced by pre‐incubation of control cells with recombinant IL‐4. LPS stimulation also decreased TLR‐4 expression on monocytes from children without atopic histories but not from atopic subjects. CD4+ T lymphocytes showed limited LPS responsiveness, regardless of atopic status. In contrast with non‐atopic children, TLR‐4 expression on monocytes of children with atopic histories decreased as a function of age.Conclusions
This study provides evidence for defective LPS recognition on circulating CD4+ leucocytes of subjects with atopic histories compared with those from non‐atopic children. CD4+TLR4+ monocytes from children with atopic histories failed to phosphorylate MAPKs. Our results suggest that a history of atopic disease is associated with impaired TLR‐4‐mediated innate immune function compared with non‐atopic children. Cite this as: D. Préfontaine, A.‐A. Banville‐Langelier, P.‐O. Fiset, J. Guay, J. An, M. Mazer, Q. Hamid and B. D. Mazer, Clinical & Experimental Allergy, 2010 (40) 1648–1657.
Socio‐economic status, geographic remoteness and childhood food allergy and anaphylaxis in Australia
Authors: Mullins R. J. , Clark S. , Camargo C. A. 
Published: July 2010

SummaryBackground
The risk factors for food allergy (FA) and anaphylaxis remain uncertain.Objective
We examined the association between socio‐economic status (SES), geographic remoteness and childhood FA and anaphylaxis in Australia.Methods
Sales of infant hypoallergenic formulae (IHF; 2008–2009) and EpiPens (2006–2007) in children aged 0–4 years and hospital anaphylaxis admission rates (2002–2006) in age groups 0–4, 5–14, 15–24, 25–64 and 65+ years were used as proxy markers of FA and anaphylaxis in Australia. Government and commercially derived data were analysed by SES and geographic remoteness (very remote, remote, outer regional, inner regional and major cities).Results
Annual IHF sales rates were higher in those with the greatest compared with the least socio‐economic advantage (47 830 vs. 21 384 tins/100 000 population; P<0.001). EpiPen sales trends were also higher in those with the greatest socio‐economic advantage in all age groups, most marked in those aged 0–4 (1713 vs. 669/100 000; P=0.002) and 5–14 years (1628 vs. 600/100 000; P=0.001). Formula sales rates were higher in major cities than remote/very remote regions (37 421 vs. 6704/100 000; P<0.001) with similar EpiPen sales trends, particularly in ages 0–4 (1166 vs. 601/100 000; P=0.045) and 5–14 years (1099 vs. 588/100 000; P<0.001). Socio‐economic advantage and geographic remoteness remained statistically significant in multivariable analysis of prescription rates (P<0.01) and were unchanged by adjustment for health services access. While anaphylaxis admission rates were higher in those with the greatest compared with the least socio‐economic advantage in children aged 0–4 years (129 vs. 92/100 000 population/year; P=0.03), the opposite was observed in older age groups (e.g. aged 25–64 years: 43 vs. 76, P=0.01). There was no association between geographic remoteness and anaphylaxis admissions.Conclusion
Socio‐economic advantage and residence in major cities may be risk factors for developing childhood FA and anaphylaxis. Further study will determine the extent to which economic factors and location of residence also influence access to health services. Cite this as: R. J. Mullins, S. Clark and C. A. Camargo Jr., Clinical & Experimental Allergy, 2010 (40) 1523–1532.
Circulating CD14+CD16+ monocyte levels predict tissue invasive character of cholangiocarcinoma
Authors: Subimerb C , Pinlaor S , Lulitanond V , Khuntikeo N , Okada S , McGrath M S , Wongkham S 
Published: July 2010

SummaryChronic inflammation as a risk factor for cancer development is driven in part by monocyte/macrophages, which in many cancers exhibit pro-tumorigenic activity. In this study we identified elevation in CD14+CD16+, a minor blood monocyte subpopulation in cholangiocarcinoma (CCA) patients, compared to normal and biliary disease patient specimens. Tumour association was suggested by the observation that this elevated level decreased to normal after tumour resection. Moreover, the elevated level of CD14+CD16+ monocytes in CCA patient blood correlated with degree of MAC387-positive (recent blood-derived macrophage migrant-specific marker) tumour-associated macrophage infiltration as determined by immunohistochemistry. These CD14+CD16+ monocytes were suggested to enhance tumour progression as this subpopulation possesses (i) high expression of adhesion molecules (CD11c, CD49d, and CD54) and scavenger receptor (CD163), which enable them to adhere strongly to endothelial cells, and (ii) that peripheral blood monocytes from CCA patients express high levels of growth and angiogenic factor-related genes (epiregulin, VEGF-A and CXCL3). Elevation of peripheral CD14+CD16+ monocyte levels was associated with features associated with poor prognosis CCA parameters (non-papillary type and high number of tissue macrophages). These data indicate that the CD14+CD16+ monocytes from CCA patients with pro-tumorigenic characteristics may associate with rapid tumour progression and poor patient outcome. If confirmed in subsequent studies, the level of CD14+CD16+ monocytes may serve as a marker for disease activity in CCA patients and serve as a target for pathogenic macrophage specific drug development.