bluuebunny/crossref_metadata_2025_split huggingface dataset:
Familial haemophagocytic lymphohistiocytosis: advances in the genetic basis, diagnosis and management
Authors: Gholam C , Grigoriadou S , Gilmour K C , Gaspar H B 
Published: February 2011

Summary
Familial haemophagocytic lymphohistiocytosis (FHL) is a rare autosomal recessive disorder of immune dysregulation associated with uncontrolled T cell and macrophage activation and hypercytokinaemia. The incidence of FHL is 0·12/100·000 children born per year, with a male to female ratio of 1:1. The disease is classified into six different types based on genetic linkage analysis and chromosomal localization; five specific genetic defects have been identified, which account for approximately 90% of all patients. Type 1 is due to an as yet unidentified gene defect located on chromosome nine. Type 2 is caused by mutations in the perforin (PRF1) gene, type 3 by mutations in the Munc-13–4 (UNC13D) gene, type 4 by mutations in the syntaxin 11 (STX11) gene and the recently described type 5 due to mutations in the gene encoding syntaxin binding protein 2 (STXBP-2). The incidence of the five types varies in different ethnic groups. The most common presenting features are pyrexia of unknown origin, pronounced hepatosplenomegaly and cytopenias. Neurological features tend to present later and are associated with poor prognosis. Absent or decreased lymphocyte cytotoxicity is the cellular hallmark of FHL. Biochemical features such as hyperferritinaemia, hypertriglyceridaemia and hypofibrinogenaemia are usually present, along with high levels of soluble interleukin 2 receptor in the blood and cerebrospinal fluid. Bone marrow aspirate may demonstrate the characteristic haemophagocytes, but initially is non-diagnostic in two-thirds of patients. Established international clinical, haematological and biochemical criteria now facilitate accurate clinical diagnosis. The disease is fatal unless a haematopoietic stem cell transplant (HSCT) is performed. The introduction of HSCT has dramatically improved the prognosis of the disease. However, the mortality of the disease is still significantly high and a number of challenges remain to be addressed. Active disease at the time of the transplant is the major significant poor prognostic factor. Delayed diagnosis, after irreversible organ damage has occurred, especially neurological damage, disease reoccurrence and pre-transplant mortality, remain a concern.
Elevated blood levels of inflammatory monocytes (CD14+CD16+) in patients with complex regional pain syndrome
Authors: Ritz B W , Alexander G M , Nogusa S , Perreault M J , Peterlin B L , Grothusen J R , Schwartzman R J 
Published: February 2011

Summary
Complex regional pain syndrome (CRPS) is a chronic pain disorder. Although its pathophysiology is not completely understood, neurogenic inflammation is thought to play a significant role. Microglia and astrocytes are activated following tissue injury or inflammation and have been reported to be both necessary and sufficient for enhanced nociception. Blood-borne monocytes/macrophages can infiltrate the central nervous system (CNS) and differentiate into microglia resulting in hypersensitivity and chronic pain. The primary aim of this study was to evaluate the proportion of the proinflammatory CD14+CD16+ monocytes as well as plasma cytokine levels in blood from CRPS patients compared to age- and gender-matched healthy control individuals. Forty-six subjects (25 CRPS, 21 controls) were recruited for this study. The percentage of monocytes, T, B or natural killer (NK) cells did not differ between CRPS and controls. However, the percentage of the CD14+CD16+ monocyte/macrophage subgroup was elevated significantly (P &lt; 0·01) in CRPS compared to controls. Individuals with high percentage of CD14+CD16+ demonstrated significantly lower (P &lt; 0·05) plasma levels on the anti-inflammatory cytokine interleukin (IL)-10. Our data cannot determine whether CD14+CD16+ monocytes became elevated prior to or after developing CRPS. In either case, the elevation of blood proinflammatoty monocytes prior to the initiating event may predispose individuals for developing the syndrome whereas the elevation of blood proinflammatory monocytes following the development of CRPS may be relevant for its maintenance. Further evaluation of the role the immune system plays in the pathogenesis of CRPS may aid in elucidating disease mechanisms as well as the development of novel therapies for its treatment.
Smoking and periodontal disease: discrimination of antibody responses to pathogenic and commensal oral bacteria
Authors: Hayman L , Steffen M J , Stevens J , Badger E , Tempro P , Fuller B , McGuire A , Al-Sabbagh Mohanad , Thomas M V , Ebersole J L 
Published: February 2011

Summary
Smoking is an independent risk factor for the initiation, extent and severity of periodontal disease. This study examined the ability of the host immune system to discriminate commensal oral bacteria from pathogens at mucosal surfaces, i.e. oral cavity. Serum immunoglobulin (Ig)G antibody reactive with three pathogenic and five commensal oral bacteria in 301 current smokers (age range 21–66 years) were examined by enzyme-linked immunosorbent assay. Clinical features of periodontal health were used as measures of periodontitis. Antibody to the pathogens and salivary cotinine levels were related positively to disease severity; however, the antibody levels were best described by the clinical disease unrelated to the amount of smoking. The data showed a greater immune response to pathogens than commensals that was related specifically to disease extent, and most noted in black males. Significant correlations in individual patient responses to the pathogens and commensals were lost with an increasing extent of periodontitis and serum antibody to the pathogens. Antibody to Porphyromonas gingivalis was particularly distinct with respect to the discriminatory nature of the immune responses in recognizing the pathogens. Antibody responses to selected pathogenic and commensal oral microorganisms differed among racial groups and genders. The antibody response to the pathogens was related to disease severity. The level of antibody to the pathogens, and in particular P. gingivalis, was correlated with disease severity in black and male subsets of patients. The amount of smoking did not appear to impact directly serum antibody levels to these oral bacteria.
Expression and function of the autoimmune regulator (Aire) gene in non-thymic tissue
Authors: Eldershaw S A , Sansom D M , Narendran P 
Published: February 2011

SummaryEducational immune tolerance to self-antigens is induced primarily in the thymus where tissue-restricted antigens (TRAs) are presented to T lymphocytes by cells of the thymic stroma – a process known as central tolerance. The expression of these TRAs is controlled in part by a transcription factor encoded by the autoimmune regulatory (Aire) gene. Patients with a mutation of this gene develop a condition known as autoimmune–polyendocrinopathy–candidiasis–ectodermal–dystrophy (APECED), characterized by autoimmune destruction of endocrine organs, fungal infection and dental abnormalities. There is now evidence for TRA expression and for mechanisms of functional tolerance outside the thymus. This has led to a number of studies examining Aire expression and function at these extra-thymic sites. These investigations have been conducted across different animal models using different techniques and have often shown discrepant results. Here we review the studies of extra thymic Aire and discuss the evidence for its expression and function in both human and murine systems.
Serum insulin‐like growth factor I and its binding protein 3 in their relation to intima–media thickness: results of the study of health in Pomerania (SHIP)
Authors: Spilcke‐Liss Elisabeth , Friedrich Nele , Dörr Marcus , Schminke Ulf , Völzke Henry , Brabant Georg , Nauck Matthias , Wallaschofski Henri 
Published: February 2011

SummaryObjective Previous studies detected associations between lower insulin‐like growth factor I (IGF‐I) levels and increased risk of congestive heart failure or ischaemic heart disease. The aim of the present study was to assess the association of IGF‐I and its binding protein 3 (IGFBP‐3) with the carotid intima–media thickness (IMT) as marker of asymptomatic cardiovascular disease.Design and population From the population‐based Study of Health in Pomerania (SHIP), a total of 2286 participants aged 45 years or older with readable ultrasound of the carotid arteries were available for the present analyses.Methods and measurements Serum IGF‐I and IGFBP‐3 levels were categorized into three groups (low, moderate, high) according to the sex‐specific 10th and 90th percentile. Analyses of variance (anova) and logistic regression analyses adjusted for age, waist circumference, diabetes, hypertension and creatinine clearance were performed.Results After adjusting for confounding factors, IGF‐I and the IGF‐I/IGFBP‐3 ratio were positively related to IMT inanova. Logistic regression analyses confirmed these findings and showed that high IGF‐I levels, a high IGF‐I/IGFBP‐3 ratio and low IGFBP‐3 levels were associated to higher odds of increased IMT.Conclusion In conclusion, high IGF‐I or high IGF‐I/IGFBP‐3 ratio values and low IGFBP‐3 levels are associated with increased IMT. Therefore, systemic levels of the IGF axis or alterations in the balance of its components are associated with subclinical atherosclerotic disease.
Aromatase deficiency owing to a functional variant in the placenta promoter and a novel missense mutation in the CYP19A1 gene
Authors: Hauri‐Hohl Annik , Meyer‐Böni Monika , Lang‐Muritano Mariarosaria , Hauri‐Hohl Mathias , Schoenle Eugen J. , Biason‐Lauber Anna 
Published: February 2011

SummaryContext  Aromatase deficiency in women is a rare 46, XX disorder of sex differentiation characterized by a defect in catalysing oestrogens from androgens.Objective  To better understand this rare disorder, we searched for mutations in the CYP19A1 gene of an affected girl and analysed their functional consequences.Design and patient  We examined a girl presenting with clitoral hypertrophy at birth and mild maternal virilization (acne) during pregnancy.Main outcome measurement  A genotype–phenotype correlation was found.Results  By direct sequencing of the CYP19A1 gene, we identified a heterozygous A>G mutation (c. A1374G) mutation in exon IX, leading to the missense p.N411S in the P450Aro protein and a heterozygous placenta promoter variant −41 base pairs upstream of exon I.1. Aromatase enzyme activity was completely lost when the mutant p.N411S protein was expressed in COS‐1 cells. The placenta promoter variant had a significantly reduced (−50%) transactivation ability compared to wild‐type.Conclusion  Our data describe a novel loss‐of‐function missense mutation in CYP19A1 combined with the first‐described variant of the placenta promoter with a significant reduction in function, likely to be the molecular basis of this rare 46, XX disorder of sex development. This seems to represent a unique case of aromatase deficiency occurring in utero only.
Hollow spheroids in ascites of ovarian clear cell carcinoma: how are they formed and how do they behave?
Authors: Kato N. , Narutomi K. , Fukase M. , Motoyama T. 
Published: February 2011

N. Kato, K. Narutomi, M. Fukase and T. MotoyamaHollow spheroids in ascites of ovarian clear cell carcinoma: how are they formed and how do they behave?Objective:  Although the multicellular aggregates (spheroids) in malignant ascites are usually solid throughout, they sometimes have acellular hollow spaces, especially in ascites of ovarian clear cell carcinoma. The purpose of this study is to analyse the origin and behaviour of hollow spheroids.Methods:  Archival cytological and histological specimens of 32 ovarian carcinomas, including 12 clear cell carcinomas, were reviewed. HAC‐2, a clear cell carcinoma cell line, was injected into the abdominal cavity of nude mice for direct comparison of ascitic cytology and tumour histology. Spheroids that were collected from nude mice ascites were cultured in vitro to observe their behaviour.Results:  Five of six clear cell carcinomas with hollow spheroids showed spherule‐like hyaluronan‐rich stroma in their tumour tissue, whereas those without hollow spheroids did not. After heterotransplantation, both ascites and tumour imprints showed small or large hollow spheroids. Hyaluronan was detected in the former but not in the latter. The abdominal tumours showed compact spherule‐like hyaluronan‐rich stroma, enlarged oedematous stroma or intermediate stroma. In both size and hyaluronan status, small and large hollow spheroids were approximately comparable to spherule‐like hyaluronan‐rich stroma and oedematous stroma, respectively. During culture in vitro, hollow spheroids were maintained as hollow spheroids in suspension, and produced daughter hollow spheroids.Conclusions:  The hollow space in the spheroids originates from spherule‐like hyaluronan‐rich stroma, where water trapping by hyaluronan causes enlargement of the space. The matrix within the hollow space serves as a scaffold that regulates cell polarity and matrix production.
GrazeIn: a model of herbage intake and milk production for grazing dairy cows. 3. Simulations and external validation of the model
Authors: Delagarde R. , Valk H. , Mayne C. S. , Rook A. J. , González‐Rodríguez A. , Baratte C. , Faverdin P. , Peyraud J. L. 
Published: February 2011

AbstractGrazeIn is a model for predicting herbage intake and milk production of grazing dairy cows. The objectives of this paper are to test its robustness according to a planned arrangement of grazing and feeding scenarios using a simulation procedure, and to investigate the precision of the predictions from an external validation procedure with independent data. Simulations show that the predicted effects of herbage allowance, herbage mass, herbage digestibility, concentrate supplementation, forage supplementation and daily time at pasture are consistent with current knowledge. The external validation of GrazeIn is investigated from a large dataset of twenty experiments representing 206 grazing herds, from five research centres within Western Europe. On average, mean actual and predicted values are 14·4 and 14·2 kg DM d−1 for herbage intake and 22·7 and 24·7 kg d−1 for milk production, respectively. The overall precision of the predictions, estimated by the mean prediction error, are 16% (i.e. 2·3 kg DM d−1) and 14% (i.e. 3·1 kg d−1) for herbage intake and milk production, respectively. It is concluded that the GrazeIn model is able to predict variations in herbage intake and milk production of grazing dairy cows in a realistic manner over a wide range of grazing management practices, rendering it suitable as a basis for decision support systems.
GrazeIn: a model of herbage intake and milk production for grazing dairy cows. 1. Prediction of intake capacity, voluntary intake and milk production during lactation
Authors: Faverdin P. , Baratte C. , Delagarde R. , Peyraud J. L. 
Published: February 2011

AbstractThe prediction of both food intake and milk production constitutes a major issue in ruminants. This article presents a model predicting voluntary dry matter intake and milk production by lactating cows fed indoors. This model, with an extension to predict herbage intake at grazing presented in a second article, is used in the Grazemore decision support system. The model is largely based on the INRA fill unit system, consisting of predicting separately the intake capacity of the cows and the fill value (ingestibility) of each feed. The intake capacity model considers potential milk production as a key component of voluntary feed intake. This potential milk production represents the energy requirement of the mammary gland, adjusted by protein supply when the protein availability is limiting. Actual milk production is predicted from the potential milk production and from the nutritional status of the cow. The law of response of milk production is a function of the difference between energy demand and actual energy intake, modulated by protein intake level. The simulation of experimental data from different feeding trials illustrates the performance of the model. This new model enables dynamic simulations of intake and milk production sensitive to feeding management during the whole lactation period.
Programmed death ligand 2 regulates arginase induction and modifies Trypanosoma cruzi survival in macrophages during murine experimental infection
Authors: Dulgerian Laura R. , Garrido Vanina V. , Stempin Cinthia C. , Cerbán Fabio M. 
Published: February 2011

SummaryThe programmed death ligands 1 (PD‐L1) and 2 (PD‐L2) that bind to programmed death 1 (PD‐1) have been involved in peripheral tolerance and in the immune escape mechanisms during chronic viral infections and cancer. However, there are no reports about the role of these molecules during Trypanosoma cruzi infection. We have studied the role of PD‐L1 and PD‐L2 in T. cruzi infection and their importance in arginase/inducible nitric oxide synthase (iNOS) balance in the immunomodulatory properties of macrophages (Mφ). In this work, we have demonstrated that expression of the PD‐1/PD‐L pathway is modified during T. cruzi infection on Mφs obtained from peritoneal cavity. The Mφs from T. cruzi‐infected mice suppressed T‐cell proliferation and this was restored when anti‐PD‐1 and anti‐PD‐L1 antibodies were added. Nevertheless, anti‐PD‐L2 antibody treatment did not re‐establish T‐cell proliferation. PD‐L2 blockade on peritoneal cells from infected mice showed an increase in arginase expression and activity and a decrease in iNOS expression and in nitric oxide (NO) production. Additionally, interleukin‐10 production increased whereas interferon‐γ production was reduced. As a result, this microenvironment enhanced parasite proliferation. In contrast, PD‐1 and PD‐L1 blockage increased iNOS expression and NO production on peritoneal Mφs from T. cruzi‐infected mice. Besides, PD‐L2 knockout infected mice showed an increased in parasitaemia as well as in arginase activity, and a reduction in NO production. Taken together, our results demonstrate that PD‐L2 is involved in the arginase/iNOS balance during T. cruzi infection having a protective role in the immune response against the parasite.
The alveolar bone height of the primary and first permanent molars in healthy 6‐ to 9‐year‐old Jordanian children
Authors: Al Jamal Ghaida , Al‐Batayneh Ola B , Hamamy Dima 
Published: February 2011

AimTo establish a threshold cemantoenamel junction (CEJ)–alveolar bone crest (ABC) distance in healthy 6‐ to 9‐year‐old Jordanian children and determine the effect of pathological changes, physiological changes, gender, and age on the CEJ–ABC distance.DesignBitewing radiographs were made for 539 6‐ to 9‐year‐old children. Plaque index (PI), gingival index (GI), calculus index (CI), DMFS score, and pocket depth were all assessed through clinical examination. CEJ–ABC distance was measured from radiographs at the mesial surface of permanent first molars (PFM), and the mesial and distal surfaces of primary molars.ResultsThe CEJ–ABC distance ranged from 0.00 to 4.49 mm, the mean for all surfaces was 0.84 ± 0.44 mm, no gender or age group differences were found. The mesial surface of the PFMs had the smallest mean CEJ–ABC distance. The CEJ–ABC distances were greater in the maxilla than in the mandible. No significant effect of PI, GI or CI on CEJ–ABC distance was found. Caries, faulty restorations, exfoliation, and partial eruption adjacent to measured surfaces had significant effect on the CEJ–ABC distance.ConclusionThe mean CEJ–ABC distance was <1 mm. Threshold CEJ–ABC distances of 1.0 and 1.5 mm for PFMs and primary molars, respectively, are suggested to be used in 6‐ to 9‐year‐old children.
Adaptive divergence for a fitness‐related trait among invasiveAmbrosia artemisiifoliapopulations in France
Authors: CHUN YOUNG JIN , LE CORRE VALÉRIE , BRETAGNOLLE FRANÇOIS 
Published: February 2011

AbstractThe impact of natural selection on the adaptive divergence of invasive populations can be assessed by testing the null hypothesis that the extent of quantitative genetic differentiation (QST) would be similar to that of neutral molecular differentiation (FST). Using eight microsatellite loci and a common garden approach, we comparedQSTandFSTamong ten populations of an invasive speciesAmbrosia artemisiifolia(common ragweed) in France. In a common garden study with varying water and nutrient levels, we measuredQSTfor five traits (height, total biomass, reproductive allocation, above‐ to belowground biomass ratio, and days to flowering). Although lowFSTindicated weak genetic structure and strong gene flow among populations, we found significant diversifying selection (QST > FST) for reproductive allocation that may be closely related to fitness. It suggests that abiotic conditions may have exerted selection pressure onA. artemisiifoliapopulations to differentiate adaptively, such that populations at higher altitude or latitude evolved greater reproductive allocation. As previous studies indicate multiple introductions from various source populations ofA. artemisiifoliain North America, our results suggest that the admixture of introduced populations may have increased genetic diversity and additive genetic variance, and in turn, promoted the rapid evolution and adaptation of this invasive species.
A new family of quorum sensing pheromones synthesized using S‐adenosylmethionine and Acyl‐CoAs
Authors: Winans Stephen C. 
Published: February 2011

SummaryIt is now widely accepted that populations of bacterial cells often co‐ordinate their behaviour via diffusible chemical signals. Many different signals have been documented, but they fall into a relatively small number of families. One such signal, CAI‐1, from Vibrio cholerae consists of a substituted 13‐carbon alkane. In this issue, Bassler and colleagues provide evidence that CAI‐1 exemplifies an entirely new class of pheromones. They also show that one species of Vibrio synthesizes and detects just one such pheromone, while another species synthesizes and detects several. Bioinformatics and data from another group indicate that this new class of signals may be widespread among beta‐ and gamma‐proteobacteria.