bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D deficiency in children with haemophilia
Authors: GOWDA MADHU , MASSEY GITA , KUMAR ANIL RAMASWAMY , KHAN ASADULLAH , NOLTE MELINDA , KUHN JANICE 
Published: March 2009

Background:  Recent studies have shown that children with severe haemophilia could have moderately reduced bone density compared with gender‐ and age‐matched control subjects. Patients with more established changes resulting from haemophilic joint disease exhibited the lowest bone mineral density. The reason for this includes factors such as lack of weight‐bearing physical activity, lower height and weight reached by these patients, muscle atrophy and hepatitis C seropositivity. A lower peak bone density reached during late adolescence and young adulthood predisposes to the development of osteoporosis in the later years.Objective:  While Vitamin D and calcium supplementation has been recommended by many authors for haemophiliacs, there are no studies looking at Vitamin D levels in these patients. The aim of this study was to evaluate for the prevalence of Vitamin D deficiency and the need for supplementation in the haemophiliac patients in our centre.Methods:  The 25‐hydroxy Vitamin D3 (25‐OH D3), calcium, phosphorus and PTH levels were measured in patients between the ages of 1–18 years during their regular visits to the haemophilia centre. A 25‐OH D3 level of >30ng mL−1 is considered as adequate, levels of 21–29 ng mL−1 indicates a relative insufficiency and a level <20ng mL−1 is defined by most experts as being absolutely Vitamin D deficient.Results:  Of the 33 patients, 21 of them were Vitamin D deficient (63.6%). Calcium, phosphorus and PTH levels did not correlate with Vitamin D levels.Conclusions:  Vitamin D deficiency is highly prevalent in patients with haemophilia in our centre, and given their propensity to develop osteopenia, Vitamin D supplementation is essential in this group of patients. As the calcium, phosphorus and PTH level do not correlate with Vitamin D levels, evaluation of Vitamin D deficiency needs the measurement of serum 25‐hydroxy D3 level. The reasons for a deficiency of Vitamin D in these patients, the amount of supplementation needed and the effect of supplementation of Vitamin D on attaining the peak bone mass density of these patients need to be explored further.  Vitamin D status in patients with haemophilia (25‐OH D3 level)

>30 ng mL−1 (normal)
21–29 ng mL−1 (relative insufficiency)
<20 ng mL−1 (severe insufficiency)

<30 ng mL−1 (vitamin D deficiency)

Haemophilia A&B (# of patients)
12
9
12

21/33 = 63.6%
Dose response results of self complementary adeno‐associated virus (AAV) vector‐mediated factor IX gene transfer in non‐human primates
Authors: REISS ULRIKE , DAVIDOFF ANDREW , GRAY JOHN , NIENHUIS ARTHUR , NATHWANI AMIT 
Published: March 2009

Objective:  In anticipation of opening a phase I/II clinical trial of adeno‐associated virus (AAV) vector‐mediated factor IX (FIX) gene transfer in subjects with severe haemophilia B, we have recently evaluated the vector dose‐response relationship in nonhuman primates. Our approach differs from prior studies in that the vector (scAAV2/8‐LP1‐hFIXco) used, will: (i) be pseudotyped with serotype 8 capsid; (ii) be delivered by peripheral vein; and (iii) have a self‐complementary genome.Methods:  The vector scAAV2/8‐LP1‐hFIXco was produced by calcium phosphate mediated two plasmid transient transfection of 293T cells with the virus then being purified using group separation and ion exchange chromatography in our GMP facility, using exactly the same methodology that we propose to use for production of the clinical lot. The titre of the vector prep was determined by qPCR analysis. Male rhesus macaques, previously screened for the absence of serotype 8 humoral immunity, received vector via bolus infusion over 15 min through a peripheral vein. Human FIX expression in the rhesus plasma collected at serial time points following vector administration was determined by our previously validated ELISA.Summary:  We used four vector dose levels, 2 × 1010, 6 × 1010, 2 × 1011 and 2 × 1012 vg kg−1 body weight, in cohorts of three or four macaques each. No overt toxicity or perturbation in serum biochemistries or other laboratory values was noted in any animal. A nearly linear dose‐response relationship between vector administered and hFIX expression was observed. Mean levels of human FIX 3 weeks following vector administration, expressed as a percentage of normal (5ug mL−1), was as follows: 2% (2 × 1010), 6% (6 × 1010), 25% (2 × 1011) and 200% (2 × 1012) and has remained relatively stable. Of the four macaques given a dose of 2 × 1010 vg kg−1, one initially had a FIX level of nearly 10% that has remained at 8% for several weeks. A second animal peaked at 1% but hFIX is now undetectable. Two macaques never had detectable hFIX expression. Tissue biopsies have demonstrated by qPCR analysis that the vast majority of vector genomes are found in the liver, although they can be detected at other sites including the testis.Conclusions:  Based on these results, we plan to use 2 × 1010 vg kg−1 as the starting dose in our upcoming clinical trial. We believe that some participants may achieve the target level of 3% hFIX expression at this dose, if we can extrapolate the information we have obtained in rhesus macaques to humans. However, we are prepared to quickly dose‐escalate if this is not the case. Our maximal clinical dose will be 2 × 1011 vg kg−1, 10‐fold lower than the highest dose in this preclinical study (2 × 1012 vg kg−1), a dose that was found to be safe and without toxicity.
Bacterial signalling overrides cytokine signalling and modifies dendritic cell differentiation
Authors: Davies Julie M. , Sheil Barbara , Shanahan Fergus 
Published: March 2009

SummaryHeterogeneity of dendritic cells (DC) is evident in the gut‐associated lymphoid tissue and determined, in part, by incompletely understood local environmental factors. Bacterial signalling is likely to be a dominant influence on precursor cells when recruited to the mucosa. We assessed the influence of commensal bacteria on DC differentiation and function. Murine bone marrow progenitors were exposed to Lactobacillus salivarius, Bifidobacterium breve or Bifidobacterium infantis. Differences in cell surface phenotype and function were assessed. Myeloid differentiation factor 88−/− (MyD88) cells were used to determine the influence of Toll‐like receptor signalling. While bacterial strains varied in impact, there was a consistent dose‐dependent inhibition of DC differentiation with a shift toward a Gr‐1+ CD11b+ monocyte‐like phenotype. A single bacterium on a per cell basis (1 : 1) was sufficient to alter cell phenotype. The effect was only evident in early precursors. Enhanced interleukin‐10 production correlated with increased Forkhead box P3 expression and reduced T‐cell proliferation. The bacterial effect on DC differentiation was found to be MyD88‐dependent. Signalling by enteric commensals through pattern recognition receptors on precursor cells alters DC differentiation and results in cells that are phenotypically monocyte‐like and functionally suppressive. This may account for some of the features of mucosal immune tolerance to the microbiota.
Interaction of human peripheral blood monocytes with apoptotic polymorphonuclear cells
Authors: Mikołajczyk Tomasz P. , Skrzeczyńska‐Moncznik Joanna E. , Zarębski Mirosław A. , Marewicz Ewa A. , Wiśniewska Anna M. , Dzięba Magdalena , Dobrucki Jerzy W. , Pryjma Juliusz R. 
Published: March 2009

SummaryMacrophages have the potential to recognize apoptotic neutrophils and phagocytose them while the same function for monocytes is uncertain. In fact, early findings indicated that monocytes started to phagocytose neutrophils on the third day of differentiation to macrophages. Here we show, using flow cytometry and confocal microscopy, that peripheral blood monocytes phagocytose apoptotic but not freshly isolated granulocytes. Recognition of apoptotic cells is predominantly connected with CD16+ monocytes (CD14high CD16+ and CD14dim CD16+) and requires CD36. Clearance of apoptotic polymorphonuclear leucocytes appears to be independent of the CD14 mechanism. Uptake of apoptotic Jurkat T cells by monocytes is CD14 and CD36 dependent. Liposomes containing phosphatidyl‐l‐serine reduce binding of apoptotic polymorphonuclear leucocytes. Lipopolysaccharide‐activated subpopulations of monocytes while in contact with apoptotic cells produce more anti‐inflammatory cytokine interleukin‐10 whereas the production of pro‐inflammatory cytokines, tumour necrosis factor‐α and interleukin‐1β is reduced.
The secreted form of p28 subunit of interleukin (IL)‐27 inhibits biological functions of IL‐27 and suppresses anti‐allogeneic immune responses
Authors: Shimozato Osamu , Sato Ayako , Kawamura Kiyoko , Chiyo Masako , Ma Guangyu , Li Quanhai , Tagawa Masatoshi 
Published: March 2009

SummaryInterleukin‐27 (IL‐27) is a new IL‐12‐related heterodimeric cytokine comprising a novel p28 molecule and the Epstein–Barr‐virus‐induced gene 3 (EBI3) molecules. It augments initiation of T helper type 1‐mediated immunity by enhancing the proliferation and cytokine production of T cells. In this study, we examined whether a secreted form of IL‐27 subunits would inhibit IL‐27‐mediated immunological responses. COS‐7 cells transduced with the mouse (m) p28 gene secreted a monomeric mp28 protein; however, those transduced with the mEBI3 gene did not detect a mEBI3 protein in the culture supernatants. The secreted mp28 prevented the IL‐27‐mediated signal transduction and activator of transcription 1 phosphorylation and subsequently inhibited the IL‐27‐mediated intercellular adhesion molecule‐1 induction and interferon‐γ production in CD4+ T cells. We generated mp28‐expressing murine carcinoma Colon 26 cells and inoculated a mixture of the mp28‐ and mIL‐27‐expressing Colon 26 cells into syngeneic BALB/c mice. Simultaneous production of mp28 and mIL‐27 from Colon 26 cells suppressed IL‐27‐mediated anti‐tumour effects in the mice. We examined the p28‐mediated immune suppression by inoculating mp28‐expressing myoblasts into allogeneic mice. Forced production of mp28 suppressed the allogeneic cytotoxic T‐lymphocyte induction and subsequently retarded the graft rejection. Furthermore, production of both mp28 and mp40, which inhibits the functions of IL‐12 and IL‐23, prolonged the graft survival longer than the grafts expressing either mp28 or mp40. We propose that p28 can be a regulatory subunit for IL‐27‐mediated cellular immune responses and a possible therapeutic agent to suppress unfavourable immune responses.
Disequilibrium of T helper type 1, 2 and 17 cells and regulatory T cells during the development of experimental autoimmune myasthenia gravis
Authors: Mu Lili , Sun Bo , Kong Qingfei , Wang Jinghua , Wang Guangyou , Zhang Shujuan , Wang Dandan , Liu Yumei , Liu Yixi , An Huixia , Li Hulun 
Published: March 2009

SummaryExperimental autoimmune myasthenia gravis (EAMG), an animal model of myasthenia gravis (MG), is a rare organ‐specific autoimmune disease targeting the autoantigen nicotinic acetylcholine receptor (AChR). We show here that the balance of T helper type 1 (Th1), Th2, Th17 and regulatory T (Treg) subsets of CD4+ helper T cells were redistributed during the development of EAMG and that the interleukin‐17 (IL‐17) cytokine is involved in this disease. The ratio of Th17 cells changed most notably with disease progression accompanied by an up‐regulated level of IL‐17. Moreover, the proliferative ability of AChR peptide‐specific T cells and the anti‐AChR antibody‐secreting cells increased when stimulated by IL‐17 in vitro. These findings suggested that the disequilibrium of the CD4+ helper T‐cell subsets could promote the development of EAMG, and the pathogenic mechanism by which Th17 cells drives autoimmune responses by secreting cytokine IL‐17 provides a new target for myasthenia gravis therapy.
Modulation of dendritic cell maturation and function with mono‐ and bifunctional small interfering RNAs targeting indoleamine 2,3‐dioxygenase
Authors: Flatekval Gro F. , Sioud Mouldy 
Published: March 2009

SummaryAntigen‐presenting cells expressing indoleamine 2,3‐dioxygenase (IDO) play a critical role in maintaining peripheral tolerance. Strategies to inhibit IDO gene expression and enhance antigen‐presenting cell function might improve anti‐tumour immunity. Here we have designed highly effective anti‐IDO small interfering (si) RNAs that function at low concentrations. When delivered to human primary immune cells such as monocytes and dendritic cells (DCs), they totally inhibited IDO gene expression without impairing DC maturation and function. Depending on the design and chemical modifications, we show that it is possible to design either monofunctional siRNAs devoid of immunostimulation or bifunctional siRNAs with gene silencing and immunostimulatory activities. The latter are able to knockdown IDO expression and induce cytokine production through either endosomal Toll‐like receptor 7/8 or cytoplasmic retinoid acid‐inducible gene 1 helicase. Inhibition of IDO expression with both classes of siRNAs inhibited DC immunosuppressive function on T‐cell proliferation. Immature monocyte‐derived DCs that had been transfected with siRNA‐bearing 5′‐triphosphate activated T cells, indicating that, even in the absence of external stimuli such as tumour necrosis factor‐α, those DCs were sufficiently mature to initiate T‐cell activation. Collectively, our data highlight the potential therapeutic applications of this new generation of siRNAs in immunotherapy.
Phthalate ester‐induced thymic stromal lymphopoietin mediates allergic dermatitis in mice
Authors: Shigeno Tomomi , Katakuse Mayako , Fujita Tomoyuki , Mukoyama Yohei , Watanabe Hideki 
Published: March 2009

SummaryRecently air pollutants and irritants have been labelled as possible exogenous risk factors for allergic disorders. Although the underlying causes of allergic disorders such as atopic dermatitis and asthma remain unclear, the T helper type 2 (Th2) cell‐mediated allergic inflammatory cascade may contribute to their pathogenesis. In the last decade, it has been documented that one of the candidates for triggering Th2 commitment is thymic stromal lymphopoietin (TSLP), the expression of which is up‐regulated in the lesions of allergic patients. Here, we describe TSLP function in a fluorescein isothiocyanate (FITC) ‐induced contact hypersensitivity (CHS) model. A cytokine profile indicated that the model was dominantly mediated by the Th2 milieu. Interestingly, TSLP was increased in the skin during the sensitization phase when stimulated by a solvent, dibutyl phthalate (DBP), but not by FITC hapten or another solvent, acetone. Ear swelling in FITC‐induced CHS was totally abrogated by removing DBP from the sensitization or elicitation phase, and was restored by complementary injection of TSLP. Inversely, the ear swelling was suppressed by injection of small interfering RNA against TSLP during the sensitization phase, which was concomitant with decreasing expression of interleukin‐4 at the swollen skin site. Taken together, DBP‐induced TSLP during the sensitization phase plays a role in establishing FITC‐induced CHS and may be one of the causes of Th2 commitment in the model, suggesting that certain environmental toxins, such as DBP, may endow pro‐allergic and atopic predisposition in humans or animals.
Regulation of T‐cell immunity by leucocyte immunoglobulin‐like receptors: innate immune receptors for self on antigen‐presenting cells
Authors: Anderson Katie J. , Allen Rachel L. 
Published: March 2009

SummaryFollowing recognition of microbial patterns, innate immune receptors provide a rapid innate response and trigger antigen‐presenting cell maturation to instruct adaptive immune responses. Here we discuss a family of innate immune receptors for self – the leucocyte immunoglobulin‐like receptors (LILRs). These LILRs exert powerful inhibitory effects on antigen‐presenting cell phenotype and subsequent T‐cell responses, and may act to constrain the effects of Toll‐like receptor signalling. Despite their broad ligand specificity, differing affinities of LILRs for individual complexes of peptide–major histocompatiblity complex can determine the nature of their effect on downstream immune responses. Expression and function of LILRs may be skewed in certain conditions such as cancer or human immunodeficiency virus infection, particularly by ectopic expression of human leucocyte antigen‐G, a high‐affinity LILR ligand. We discuss the relevance of LILR‐mediated immune regulation across a range of scenarios from autoimmunity to transplant medicine, infection and cancer.
Identification and characterization of the doublesex gene of Nasonia
Authors: Oliveira D. C. S. G. , Werren J. H. , Verhulst E. C. , Giebel J. D. , Kamping A. , Beukeboom L. W. , Van De Zande L. 
Published: March 2009

AbstractThe doublesex (dsx) gene of the parasitic wasp Nasonia vitripennis is described and characterized. Differential splicing of dsx transcripts has been shown to induce somatic sexual differentiation in Diptera and Lepidoptera, but not yet in other insect orders. Two spliceforms of Nasonia dsx mRNA are differentially expressed in males and females. In addition, in a gynandromorphic line that produces haploids (normally males) with full female phenotypes, these individuals show the female spliceform, providing the first demonstration of a direct association of dsx with somatic sex differentiation in Hymenoptera. Finally, the DNA binding (DM) domain of Nasonia dsx clusters phylogenetically with dsx from other insects, and Nasonia dsx shows microsynteny with dsx of Apis, further supporting identification of the dsx orthologue in Nasonia.
Factors associated with caregivers’ perception of children's health and oral health status: a study of 6‐ to 36‐month‐olds in Uganda
Authors: WANDERA MARGARET , KAYONDO JOSEPHINE , ENGEBRETSEN INGUNN MARIE S. , OKULLO ISAAC , ÅSTRØM ANNE NORDREHAUG 
Published: March 2009

Background.  The impact of oral diseases on quality of life of children and their families has not been thoroughly investigated.Aim.  Focusing on Ugandan infants aged 6–36 months and their caregivers, this study examined the degree to which clinical and psychosocial factors were associated with caregivers’ overall evaluation of their children's oral health and health status.Design.  Eight hundred and sixteen children were examined for dental caries and anthropometric status in 2007. A questionnaire was completed by the caregivers.Results.  Poor child oral health was reported by 40.2% and 17.5% of caregivers who reported their children's health as, respectively, poor and good. Having the least family wealth [odds ratio (OR) = 1.9] and reporting distressed family activities (OR = 2.3) were associated with higher odds of reporting poor child oral health, whereas being a rural resident (OR = 0.4) and reporting no symptoms during tooth eruption (OR = 0.3) were associated with lower odds. Perception of poor child oral health (OR = 2.8) and having the least family wealth (OR = 1.7) were associated with higher odds of reporting poor child health status, whereas no stunting was associated with lower odds (OR = 0.5).Conclusion.  The results support the growing recognition of oral health as a predictor of health and well‐being in early childhood.
Influence of psychosocial factors on the development of sleep bruxism among children
Authors: SERRA‐NEGRA JUNIA M. , RAMOS‐JORGE MARIA L. , FLORES‐MENDOZA CARMEN E. , PAIVA SAUL M. , PORDEUS ISABELA A. 
Published: March 2009

Background.  Bruxism is described as an orofacial parafunction that affects both children and adults. The maintenance of the childhood habit into adulthood may compromise health. As there are few studies on this issue, there is a need for further research on sleep bruxism among children.Aim.  The aim of this study was to assess the prevalence of sleep bruxism in children and the influence of psychosocial factors.Methods.  A cross‐sectional study was carried out on 652 randomly selected children aged 7–10 years at public and private schools in Belo Horizonte, Brazil. The instruments used were: questionnaire for parents, Child Stress Scale, and the scales on neuroticism and responsibility from the prevalidated Big Five Questionnaire for Children. Psychological tests were administered and evaluated by psychologists. Sleep bruxism among children was reported by parents. The Social Vulnerability Index from the city hall database was used to determine the social classification of the families. The chi‐squared test, binary and multivariate logistic regressions were used, with the significance level set at 5%.Results.  A 35.3% prevalence of bruxism was found. No association was found between bruxism and stress, gender, age, or social vulnerability. The adjusted logistic model determined that children with high levels of neuroticism (OR = 1.9, CI 1.3–2.6) and responsibility (OR = 2.2, CI 1.0–5.0) are twice as likely to have the habit of sleep bruxism when compared to those who have low levels of these personality traits.Conclusions.  A high degree of responsibility and neuroticism, which are individual personality traits, are determinant factors for the development of sleep bruxism among children.
Assessment of the quality of reporting of randomized clinical trials in paediatric dentistry journals
Authors: AL‐NAMANKANY ABEER A. , ASHLEY PAUL , MOLES DAVID R. , PAREKH SUSAN 
Published: March 2009

Introduction.  Reporting of randomized controlled trials (RCTs) should be of high quality to support the conclusions reached by the authors. Poor‐quality reporting has been associated with an overestimation in intervention efficacy. Within the field of paediatric dentistry, no study has assessed the quality of reporting.Objective.  The aim of this study was to assess published RCTs in paediatric dental journals between 1985 and 2006 for: (i) whether quality of reporting allows readers to assess the validity of trials; and (ii) whether quality of reporting has improved since the introduction of the Consolidated Standards of Reporting Trials (CONSORT) guidelines.Methods.  Hand search of the main paediatric dentistry journals; inclusion criteria were: the trial was performed on children, and RCT. CONSORT guidelines were made into an operational checklist. Trials published between 1985 and 1997, and between 1998 and 2006 were compared to determine any improvement since the publication of the CONSORT guidelines.Results.  One hundred and seventy‐three of 5635 articles met the inclusion criteria. Reporting quality was poor overall and showed heterogeneity. It had improved slightly since the publication of CONSORT. Few trials were reported adequately.Conclusion.  The quality of reporting of clinical trials is poor, and often not adequate to allow readers to assess trial validity. Overall quality of reporting has not substantially improved since the publication of CONSORT.
Thein vitroerosive potential of a range of baby drinks
Authors: HUNTER LINDSAY , PATEL SATIN , REES JEREMY 
Published: March 2009

Objective. The aim of this study was to assess the erosive potential of a range of commercially available baby drinks in the laboratory.Methods. The erosive potential of each product was assessed by measuring its initial pH, neutralizable acidity, and ability to erode primary and permanent enamel. These parameters were compared to those of an orange juice positive control.Results. The initial pH of the baby drinks ranged from 3.5 to 4.0 with their neutralizable acidity ranging from 5.76 to 16.02 mL of 0.1 mNaOH. The amount of primary enamel removed following 1‐h immersion in the drinks ranged from 3.77 to 8.10 microns, while the amount of permanent enamel removed ranged from 1.09 to 4.86 microns. In comparison, the orange juice control (Tropicana smooth) had an initial pH of 3.86, a neutralizable acidity of 37.0 mL of 0.1 mNaOH, and removed 6.39 microns of primary enamel and 5.32 microns of permanent enamel.Conclusion. All the baby drinks tested were found to be erosive; some of the products were as erosive as orange juice.