bluuebunny/crossref_metadata_2025_split huggingface dataset:
Serum regulates cortisol bioactivity by corticosteroid‐binding globulin‐dependent and independent mechanisms, as revealed by combined bioassay and physicochemical assay approaches
Authors: Perogamvros I. , Kayahara M. , Trainer P. J. , Ray D. W. 
Published: February 2011

SummaryContext  Corticosteroid‐binding globulin (CBG) is the principal carrier of natural glucocorticoids in the circulation, and we hypothesized that it modulates glucocorticoid bioactivity (GBA). Alterations in CBG, the presence of noncortisol, naturally occurring glucocorticoids and the use of potent, synthetic glucocorticoids, all make it difficult to assess adrenal activity in‐vivo; these problems can be addressed by a glucocorticoid bioassay.Design and subjects  A bioassay was developed for serum GBA and a physicochemical ultrafiltration‐liquid chromatography‐tandem mass spectrometry assay for free serum cortisol (FreeF). We studied individuals homozygous and heterozygous for a nonfunctioning CBG variant (CBG G237V) and healthy controls.Results  FreeF concentrations were similar in healthy controls, and those with absent functional CBG, but surprisingly we found low GBA in CBG null individuals. This may suggest that CBG delivers cortisol to target cells. However, further experiments revealed that dilution of serum in the bioassay caused release of cortisol from CBG, resulting in elevated GBA measurements in all but the CBG G237V homozygotes. Furthermore, we identified a specific and potent inhibitory effect of high concentration serum on glucocorticoid sensitivity of the recipient cells used in the bioassay. Analysis of inflammatory synovial fluid, a filtrate of serum with lower CBG concentration, revealed elevated free cortisol compared to noninflammatory synovial fluid, a change not attributable to interconversion between cortisol and cortisone.Conclusions  Our findings reveal that dilution of CBG enhances cortisol release, and so bioactivity, and also that serum potently induces glucocorticoid resistance in target cells.
Activator‐independent transcription of Snf1‐dependent genes in mutants lacking histone tails
Authors: Infante Juan J. , Law G. Lynn , Wang I‐Ting , Chang Hsin‐Wen Ella , Young Elton T. 
Published: February 2011

SummaryTranscriptional regulation of Snf1‐dependent genes occurs in part by histone‐acetylation‐dependent binding of the transcription factor Adr1. Analysis of previously published microarray data indicated unscheduled transcription of a large number of Snf1‐ and Adr1‐dependent genes when either the histone H3 or H4 tail was deleted. Quantitative real‐time PCR confirmed that the tails were important to preserve stringent transcriptional repression of Snf1‐dependent genes when glucose was present. The absence of the tails allowed Adr1 and RNA Polymerase II to bind promoters in normally inhibitory conditions. The promoters escaped glucose repression to a limited extent and the weak constitutive ADH2 transcription induced by deletion of the histone tails was transcription factor‐ and Snf1‐independent. These effects were apparently due to a permissive chromatin structure that allowed transcription in the absence of repression mediated by the histone tails. Deleting REG1, and thus activating Snf1 in the H3 tail mutant enhanced transcription in repressing conditions, indicating that Snf1 and the H3 tail influence transcription independently. Deleting REG1 in the histone H4 tail mutant appeared to be lethal, even in the absence of Snf1, suggesting that Reg1 and the H4 tail have redundant functions that are important for cell viability.
The complex logic of stringent response regulation in Caulobacter crescentus: starvation signalling in an oligotrophic environment
Authors: Boutte Cara C. , Crosson Sean 
Published: February 2011

SummaryBacteria rapidly adapt to nutritional changes via the stringent response, which entails starvation‐induced synthesis of the small molecule, ppGpp, by RelA/SpoT homologue (Rsh) enzymes. Binding of ppGpp to RNA polymerase modulates the transcription of hundreds of genes and remodels the physiology of the cell. Studies of the stringent response have primarily focused on copiotrophic bacteria such as Escherichia coli; little is known about how stringent signalling is regulated in species that live in consistently nutrient‐limited (i.e. oligotrophic) environments. Here we define the input logic and transcriptional output of the stringent response in the oligotroph, Caulobacter crescentus. The sole Rsh protein, SpoTCC, binds to and is regulated by the ribosome, and exhibits AND‐type control logic in which amino acid starvation is a necessary but insufficient signal for activation of ppGpp synthesis. While both glucose and ammonium starvation upregulate the synthesis of ppGpp, SpoTCC detects these starvation signals by two independent mechanisms. Although the logic of stringent response control in C. crescentus differs from E. coli, the global transcriptional effects of elevated ppGpp are similar, with the exception of 16S rRNA transcription, which is controlled independently of spoTCC. This study highlights how the regulatory logic controlling the stringent response may be adapted to the nutritional niche of a bacterial species.
Th17 Cell, the New Player of Neuroinflammatory Process in Multiple Sclerosis
Authors: Jadidi‐Niaragh F. , Mirshafiey A. 
Published: February 2011

AbstractMultiple sclerosis (MS) is an autoimmune disease characterized by recurrent episodes of demyelination and axonal lesion mediated by CD4+ T cells with a proinflammatory Th1 and Th17 phenotype, macrophages, and soluble inflammatory mediators. Identification of Th17 cells led to breaking the dichotomy of Th1/Th2 axis in immunopathogenesis of autoimmune diseases such as MS, and its experimental model, experimental autoimmune encephalomyelitis (EAE). Th17 cells are characterized by expression of retinoic acid‐related orphan receptor (ROR)γt and signal transducer and activator of transcription 3 (STAT3) factors. Th17‐produced cytokine profile including interleukin (IL)‐17, IL‐6, IL‐21, IL‐22, IL‐23 and tumour necrosis factor (TNF)‐α, which have proinflammatory functions, suggests it as an important factor in immunopathogenesis of MS, because the main feature of MS pathophysiology is the neuroinflammatory reaction. The blood brain barrier (BBB) disruption is an early and central event in MS pathogenesis. Autoreactive Th17 cells can migrate through the BBB by the production of cytokines such as IL‐17 and IL‐22, which disrupt tight junction proteins in the central nervous system (CNS) endothelial cells. Consistent with this observation and regarding the wide range production of proinflammatory cytokines and chemokines by Th17 cells, it is expected that Th17 cell to be as a potent pathogenic factor in disease immunopathophysiology. Th17‐mediated inflammation is characterized by neutrophil recruitment into the CNS and neurons killing. However, the majority of our knowledge about the role of Th17 in MS pathogenesis is resulted in investigation into EAE animal models. In this review, we intend to focus on the newest information regarding the precise role of Th17 cells in immunopathogenesis of MS, and its animal model, EAE.
Monomeric and Dimeric IgG Fractions Show Differential Reactivity Against Pathogen‐Derived Antigens
Authors: Wymann S. , Zuercher A. W. , Schaub A. , Bolli R. , Stadler B. M. , Miescher S. M. 
Published: February 2011

AbstractPolyvalent Ig preparations, derived from the pooled plasma of thousands of healthy donors, contain a complex mix of both ‘acquired’ and natural antibodies directed against pathogens as well as foreign and self/auto antigens (Ag). Depending on their formulation, donor pool size, etc., liquid Ig preparations contain monomeric and dimeric IgG. The dimeric IgG fraction is thought to represent mainly idiotype‐antiidiotype Ab pairs. Treatment of all IgG fractions at pH 4 effectively monomerizes the IgG dimers resulting in separated idiotype‐antiidiotype Ab pairs and thus in a comparable F(ab’)2 binding site availability of the different IgG fractions. Previously, we identified an increased anti‐self‐reactivity within the monomerized dimer fraction. This study addressed if, among the different IgG fractions, an analogous preferential reactivity was evident in the response against different pathogen‐derived protein and carbohydrate antigens. Therefore, we assessed the activity of total unseparated IgG, the monomeric and dimeric IgG fractions against antigenic structures of bacterial and viral antigens/virulence factors. All fractions showed similar reactivity to protein antigens except for exotoxin A of Pseudomonas aeruginosa, where the dimeric fraction, especially when monomerized, showed a marked increase in reactivity. This suggests that the production of antiidiotypic IgG antibodies contributes to controlling the immune response to certain categories of pathogens. In contrast, the monomeric IgG fractions showed increased reactivity towards pathogen‐associated polysaccharides, classically regarded as T‐independent antigens. Taken together, the differential reactivity of the IgG fractions seems to indicate a preferential segregation of antibody reactivities according to the nature of the antigen.
Global Fund financing of public–private mix approaches for delivery of tuberculosis care
Authors: Lal S. S. , Uplekar Mukund , Katz Itamar , Lonnroth Knut , Komatsu Ryuichi , Yesudian Dias Hannah Monica , Atun Rifat 
Published: February 2011

SummaryObjectives  To map the extent and scope of public–private mix (PPM) interventions in tuberculosis (TB) control programmes supported by the Global Fund.Methods  We reviewed the Global Fund’s official documents and data to analyse the distribution, characteristics and budgets of PPM approaches within Global Fund supported TB grants in recipient countries between 2003 and 2008. We supplemented this analysis with data on contribution of PPM to TB case notifications in 14 countries reported to World Health Organization in 2009, for the preparation of the global TB control report.Results  Fifty‐eight of 93 countries and multi‐country recipients of Global Fund‐supported TB grants had PPM activities in 2008. Engagement with ‘for‐profit’ private sector was more prevalent in South Asia while involvement of prison health services has been common in Eastern Europe and central Asia. In the Middle East and North Africa, involving non‐governmental organizations seemed to be the focus. Average and median spending on PPM within grants was 10% and 5% respectively, ranging from 0.03% to 69% of the total grant budget. In China, India, Nigeria and the Philippines, PPM contributed to detecting more than 25% TB cases while maintaining high treatment success rates.Conclusion  In spite of evidence of cost‐effectiveness, PPM constitutes only a modest part of overall TB control activities. Scaling up PPM across countries could contribute to expanding access to TB care, increasing case detection, improving treatment outcomes and help achieve the global TB control targets.
Long‐term kidney transplant outcome in obese patients in a predominantly African American population
Authors: Karabicak Ilhan , Aytug Serhat , Lewis Shari , Shah Syed , Sumrani Nabil , Hayat Amir , Distant Dale A. , Salifu Moro O. 
Published: February 2011

Karabicak I, Aytug S, Lewis S, Shah S, Sumrani N, Hayat A, Distant DA, Salifu MO. Long‐term kidney transplant outcome in obese patients in a predominantly African American population. Clin Transplant 2011: 25: E264–E270. © 2011 John Wiley & Sons A/S.Abstract:  The impact of obesity on long‐term kidney transplant outcome has largely been studied in non‐African American patients. This study seeks to determine differences in outcome between obese and non‐obese patients after kidney transplantation, in a predominantly African American population. We reviewed 642 adult renal transplant recipients who received their transplants at SUNY Downstate Medical Center between 1998 and 2007. Sixty‐six percent of the patients studied were African American. The patients were divided into five groups according to their BMI status: underweight <20, normal 20–24.9, overweight 25–29.9, obese 30–34.9, and morbidly obese ≥35. There were no differences in race, gender, cytomegalovirus infection, type of transplant, panel‐reactive antibody, retransplant status, flow cytometry cross‐match results, mycophenolate mofetil therapy, and total HLA mismatch status. The mean discharge serum creatinine in the morbidly obese group was significantly higher than in other groups (p < 0.001). The difference in creatinine level disappeared at six wk and six months (p > 0.5), respectively. Acute rejection rates, delayed graft function, graft survival, and patient survival were not different between the groups. The findings from this large single‐center study suggest that obese and morbidly obese patients had similar outcomes compared to other weight groups. Obese and morbidly obese African American patients should not be excluded from kidney transplantation on the basis of weight alone.
Mite component–specific IgE repertoire and phenotypes of allergic disease in childhood: The tropical perspective
Authors: Kidon Mona I. , Chin Chiang Wen , Kang Liew Woei , Ching Ong Tan , Seng Tiong Yuen , Ning Wong Kang , Angus Aaron Chen , Theng Ong Seow , Feng Gao Yun , Reginald Kavita , Zhi Bi Xue , Shen Shang Hui , Tim Chew Fook 
Published: February 2011

To cite this article: Kidon MI, Chin CW, Kang LW, Ching OT, Seng TY, Ning WK, Angus AC, Theng OS, Feng GY, Reginald K, Zhi BX, Shen SH & Tim CF. Mite component–specific IgE repertoire and phenotypes of allergic disease in childhood: The tropical perspective. Pediatr Allergy and Immunol 2011; 22: 202–210.Sensitization to perennial aeroallergens correlates with the risk of persistent asthma (AS) in children. In tropical Singapore, multiple codominant species of mites abound in the indoor environment, and preferential species‐specific sensitization has been associated with different phenotypes of allergic disease. We investigated the pattern of mite component–specific IgE (mcsIgE) in children with different phenotypes of clinical allergic disease in an environment with multiple mite species exposure. A prospective evaluation of newly diagnosed patients with clinical diagnosis of allergic rhinitis (AR), atopic dermatitis (AD), or AS and sensitization to one or more aeroallergens were performed. Sera were tested for specific IgE against an extensive panel of Dermatophagoides pteronyssinus and Blomia tropicalis allergens. A total of 253 children were included, mean age 7.3 yr, 79% fulfilled criteria for AR, 46% AS, 71% AD, and 31% for all three. Sensitization to one or both mites was observed in 91% of children, 89% were sensitized to D. pteronyssinus, and 70% to B. tropicalis. The most common mite allergens recognized by these atopic children were Der p 1 (64%), Der p 2 (71%), Blo t 5 (45%), Blo t 7 (44%), and Blo t 21 (56%). Specific IgE responses to an increased number of distinct mite allergens correlated with the complexity of the allergic phenotype. In multivariate analysis, an increased risk for the multi‐systemic phenotype (AR + AS + AD) was associated with sensitization to an increased repertoire of mite components (three or more) (OR 4.3, 95% CI 2.1–8.8, p = 0.001) and a positive parental history of AS (OR 2.4, 95% CI 1.2–2.9, p = 0.013). A highly pleiomorphic IgE response to the prevalent indoor mites is associated with the presence of a multi‐systemic allergic phenotype in childhood in a tropical environment.
Allergic diseases among very preterm infants according to nutrition after hospital discharge
Authors: Zachariassen Gitte , Faerk Jan , Esberg Birgitte H. , Fenger‐Gron Jesper , Mortensen Sven , Christesen Henrik T. , Halken Susanne 
Published: February 2011

To cite this article: Zachariassen G, Faerk J, Esberg BH, Fenger‐Gron J, Mortensen S, Christesen HT, Halken S. Allergic diseases among very preterm infants according to nutrition after hospital discharge. Pediatr Allergy Immunol 2011; 22: 515–520.To determine whether a cow’s milk‐based human milk fortifier (HMF) added to mother’s milk while breastfeeding or a cow’s milk‐based preterm formula compared to exclusively mother’s milk after hospital discharge, increases the incidence of developing allergic diseases among very preterm infants (VPI) during the first year of life.Of a cohort of 324 VPI (gestational age 24–32 wk), the exclusively breastfed VPI were shortly before discharge randomized to breastfeeding without fortification or supplementing with a fortifier. Those not breastfed were fed a preterm formula. The intervention period was from discharge until 4 months corrected age (CA). Follow‐up was performed at 4 and 12 months CA including specific IgE to a panel of allergens at 4 months CA.The incidence during and prevalence at 12 months CA of recurrent wheezing (RW) was 39.2% and 32.7%, while atopic dermatitis (AD) was 18.0% and 12.1%, respectively. Predisposition to allergic disease increased the risk of developing AD (p = 0.04) [OR 2.6 (95% CI 1.0–6.4)] and the risk of developing RW (p = 0.02) [OR 2.7 (95% CI 1.2–6.3)]. Boys had an increased risk of developing RW (p = 0.003) [OR 3.1 (95% CI 1.5–6.5)]. No difference was found between nutrition groups. None developed food allergy.Compared to exclusively breastfed, VPI supplemented with HMF or fed exclusively a preterm formula for 4 months did not have an increased risk of developing allergic diseases during the first year of life.
High salivary secretory IgA antibody levels are associated with less late‐onset wheezing in IgE‐sensitized infants
Authors: Sandin Anna , Björkstén Bengt , Böttcher Malin F. , Englund Erling , Jenmalm Maria C. , Bråbäck Lennart 
Published: February 2011

To cite this article: Sandin A, Björkstén B, Böttcher MF, Englund E, Jenmalm MC, Bråbäck L. High salivary secretory IgA antibody levels are associated with less late‐onset wheezing in IgE‐sensitized infants. Pediatr Allergy Immunol 2011; 22: 477–481.Low levels of secretory IgA (SIgA) and transient IgA deficiency have been associated with an increased risk for allergy, but data are conflicting. The aim was to assess the relationship between salivary SIgA antibody levels at 1 yr and wheezing at age four in a birth cohort, in particular the possible protective role of salivary SIgA in sensitized children. Saliva samples were obtained from all children (n = 67) with a positive skin prick test (SPT) at 1 yr and 212 children with a negative SPT. In all, 200 of these children responded to questionnaires at 4 yrs and 183 were skin prick tested at that age. The levels of salivary SIgA and salivary IgA antibodies to the most common food allergen egg and inhalant allergen cat were analyzed by ELISA. Serum was analyzed for IgE antibodies to egg and cat. Development of late‐onset wheezing was associated with low SIgA levels in children with positive SPT to at least one allergen both at 1 and 4 yrs of age (p = 0.04), as well as in children with circulating IgE antibodies to egg or cat at 1 yr (p = 0.02). None of nine persistently sensitized children with SIgA levels in the upper quartile developed wheezing, when compared to 10/20 children with lower levels (p = 0.01). Older siblings, more than three infections during infancy, at least one smoking parent, and male gender, were all associated with SIgA in the upper quartile. In conclusion, high levels of SIgA antibodies in sensitized infants were associated with significantly less late‐onset wheezing, supporting a protective role against development of asthmatic symptoms. Recurrent infections and other factors supporting an increased microbial pressure during infancy were associated with high levels of salivary SIgA.
Uncontrolled asthma at age 8: The importance of parental perception towards medication
Authors: Koster Ellen S. , Wijga Alet H. , Koppelman Gerard H. , Postma Dirkje S. , Brunekreef Bert , De Jongste Johan C. , Smit Henriette A. , Hoekstra Maarten O. , Raaijmakers Jan A. M. , Maitland‐van der Zee Anke‐Hilse 
Published: February 2011

To cite this article: Koster ES, Wijga AH, Koppelman GH, Postma DS, Brunekreef B, De Jongste JC, Smit HA, Hoekstra MO, Raaijmakers JAM, Maitland‐van der Zee A‐H. Uncontrolled asthma at age 8: The importance of parental perception towards medication. Pediatr Allergy Immunol 2011; 22: 462–468.AbstractBackground:  Despite existing effective treatment options, asthma is uncontrolled in a considerable proportion of patients. The aim of this study was to identify determinants of uncontrolled asthma at age 8 in children participating in the PIAMA birth cohort study.Methods:  One hundred seventy children using inhaled corticosteroids in the previous 12 months at age 8 were included. Uncontrolled asthma was defined as: ≥3 items present in the past month: (1) day‐time or (2) night‐time asthma symptoms, (3) limitations in activities, (4) rescue medication use, (5) FEV1 < 80% predicted and (6) unscheduled physician visits because of asthma. Binomial regression was performed to study five groups of determinants representing asthma control: child and parental characteristics, environmental factors, therapy adherence and parental perception towards medication use (Beliefs about Medicines Questionnaire).Results:  Seventy seven children (45%) had uncontrolled asthma. Low maternal education (RR 1.6, 95% CI: 1.0–2.4) was associated with uncontrolled asthma. Parental necessity beliefs about medication use to maintain present and future health and parental concerns about potential adverse consequences of medication were also associated with uncontrolled asthma (RR 1.6, 95% CI: 1.1–2.2; and 1.6, 95% CI: 1.0–2.5, respectively).Conclusions:  Environmental factors and therapy adherence were not associated with asthma control. In our cohort, uncontrolled asthma is associated with low maternal education and with strong parental beliefs about medication necessity and higher concern about potential side effects of medication.
Brain size and the expression of pheomelanin‐based colour in birds
Authors: GALVÁN I. , MØLLER A. P. 
Published: February 2011

AbstractEumelanin and pheomelanin are the most common vertebrate pigments. They generate different colours and are synthesized under different physiological conditions. While pheomelanogenesis requires high levels of a key intracellular antioxidant (glutathione, GSH), eumelanogenesis is inhibited by GSH. This implies that species that present the molecular basis to produce large amounts of pheomelanin might be more limited to perform other costly processes that generate oxidative stress than species that produce eumelanin. Brain development requires large amounts of energy and antioxidants during ontogeny, so that large‐brained species may be constrained in their simultaneous synthesis of large amounts of pheomelanin, but not in their synthesis of eumelanin. Here, we tested this hypothesis in a large dataset of 323 bird species. After controlling for the effects of phylogeny, latitude and sexual dichromatism, the proportion of pheomelanic plumage colour was strongly negatively related to the relative brain mass of species, whereas no relationship was found for the proportion of eumelanic colour. This indicates that the production of pheomelanin is a costly process that cannot evolve together with complex neural structures and thus with large cognitive capacity. This is the first time that the expression of melanic traits is found to correlate with another phenotypic character across species.