bluuebunny/crossref_metadata_2025_split huggingface dataset:
The impact of risk stratification by early bone‐marrow response in childhood lymphoblastic leukaemia: results from the United Kingdom Medical Research Council trial ALL97 and ALL97/99
Authors: Mitchell Christopher , Payne Jeanette , Wade Rachel , Vora Ajay , Kinsey Sally , Richards Sue , Eden Tim 
Published: June 2009

SummaryThe 1997 acute lymphoblastic leukaemia (ALL) trial (ALL97) was a randomised comparison of prednisolone versus dexamethasone and of 6‐mercaptopurine versus 6‐thioguanine. During the first 2 years of the trial, review of survival data showed the preceding trial, UKALL XI, was no better than its predecessor and that survival for childhood ALL in the UK had not improved in the fashion witnessed by other cooperative treatment groups. The therapy template was therefore altered to an American Children’s Cancer Group (CCG) style regimen, including stratification by age, white cell count and early response to therapy by assessment of the bone marrow. This phase of the trial was designated ALL97/99. Comparison of the two phases showed that the event‐free survival (EFS) for both ALL97 and ALL97/99 was better than previous UKALL trials, as was overall survival (OS) for ALL97/99. Both EFS and OS were significantly better in ALL97/99 than in ALL97 (at five years, 80·0% vs. 74·0%, P = 0·002; and 88·0% vs. 83·5%, P = 0·005, respectively). Isolated central nervous system (CNS) relapse for patients in ALL97/99 was half that in ALL97 (3·0% vs. 4·9%), P = 0·03) and the overall CNS relapse rate was halved in ALL97/99 (4·4% vs. 9·6%, P < 0·00005). There were no significant differences for non‐CNS relapse, induction deaths or deaths in remission between the two phases of the trial.
Venous thromboembolism and ethnicity
Authors: Roberts Lara N. , Patel Raj K. , Arya Roopen 
Published: June 2009

SummaryVenous thromboembolism (VTE) has long been considered a disease that affects predominantly white populations, a misconception resulting from a paucity of epidemiological data from non‐Western countries, and the low incidence of hereditary thrombophilia in those of non‐Caucasian background. Over the last decade, interest has grown in this area with the emergence of evidence that VTE is as prevalent, if not more so, in the black population and is also common in Asian groups. Much is still to be learned, as our current knowledge of hereditary thrombophilia and acquired risk factors do not fully explain the risk of VTE in non‐Caucasian groups. This review summarises the current understanding of ethnic variation in VTE and highlights the need for further research in this area.
Timothy grass pollen major allergen Phl p 1 activates respiratory epithelial cells by a non‐protease mechanism
Authors: Röschmann K. , Farhat K. , König P. , Suck R. , Ulmer A. J. , Petersen A. 
Published: June 2009

SummaryBackground
Group 1 allergens from grass pollen (e.g. Phl p 1, the major allergen of timothy grass Phleum pratense) cause IgE reactivity in about 95% of allergic subjects and exist in all grass species. The respiratory epithelium represents a first line of contact of the immune system with airborne allergens, functions as physical barrier and is an important immunological regulation system.Objective
The aim of this study was to investigate the interaction of Phl p 1 with human respiratory epithelium to elucidate the contribution of epithelial cells to the development of allergic reactions.Methods
Purified Phl p 1 was used to stimulate A549 cells and transient transfected HEK293 cells. mRNA level of different mediators were investigated by real‐time PCR, release of the mediators was determined by ELISA. The 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide (MTT) test and an ex vivo model of the murine trachea were used to investigate a potential proteolytic activity of Phl p 1.Results
Phl p 1 activates respiratory epithelial cells as measured by induction of IL‐6, IL‐8 and TGF‐β mRNA and release. Phl p 1, in contrast to Der p 1 from the house dust mite, does not exert proteolytic activity, as investigated by microscopic observation and MTT test. In an ex vivo model of the murine trachea we were able to show that Der p 1, in contrast to Phl p 1, enhances the transportation velocity of particles by the trachea, presumably by ATP released from the injured epithelium.Conclusion
We conclude that under physiological conditions Phl p 1 affects tracheal epithelial cells through a non‐proteolytic activity. Enhancement of TGF‐β expression induced by Phl p 1 together with the increased release of IL‐6 and IL‐8 might provide an indirect mechanism through which the allergen may cross the epithelial barrier and attracts immunocompetent cells.
Basophil activation tests for the diagnosis of food allergy in children
Authors: Ocmant A. , Mulier S. , Hanssens L. , Goldman M. , Casimir G. , Mascart F. , Schandené L. 
Published: June 2009

SummaryBackground
Positive skin prick tests (SPT) for food allergens and specific IgE (sIgE) in serum indicate sensitization but do not enable distinction between sensitized but tolerant and clinically allergic patients.Objective
Herein, we evaluate the clinical relevance of basophil activation tests (BATs) for peanut or egg allergy diagnosis.Methods
Thirty‐two peanut‐allergic, 14 peanut‐sensitized (sIgE+ and/or SPT+ to peanuts) but tolerant children and 29 controls with no history of an adverse reaction to peanuts were included. Similarly, 31 egg‐allergic, 14 egg‐sensitized children (sIgE+ and/or SPT+ to egg white) and 22 controls were studied. Flow cytometric analysis of CD63 expression or CD203c upregulation on basophils and the production of leukotrienes (LT) were performed in response to an in vitro crude peanut extract or ovalbumin (OVA) challenge.Results
After in vitro peanut challenge, the basophils from peanut‐allergic children showed significantly higher levels of activation than those from controls (P<0.001). After OVA challenge, a similar distinction (P<0.001) was observed between egg‐allergics and controls. Interestingly, the majority of egg‐ or peanut‐sensitized children failed to activate basophils, respectively, in response to OVA and peanut challenge. The sensitivity of the CD63, CD203c and LT assay was 86.7%, 89.5% and 76.0% with a specificity of 94.1%, 97.1% and 94.6% for peanut allergy diagnosis. The corresponding performances of BATs applied to egg allergy diagnosis were 88.9%, 62.5% and 77.8% for the sensitivity and 100%, 96.4% and 96.4% for the specificity.Conclusion
Neither conventional tests nor BATs are sensitive and specific enough to predict food allergy accurately. However, BATs may helpfully complete conventional tests, especially SPT, allowing improved discrimination between allergic and non‐allergic individuals.
Inhaled house dust mite induces pulmonary T helper 2 cytokine production
Authors: Gregory L. G. , Causton B. , Murdoch J. R. , Mathie S. A. , O'Donnell V. , Thomas C. P. , Priest F. M. , Quint D. J. , Lloyd C. M. 
Published: June 2009

SummaryBackground
Inhaled house dust mite (HDM) results in T‐helper (TH) 2 type pathology in unsensitized mice, in conjunction with airway hyperreactivity and airway remodelling. However, the pulmonary cytokine and chemokine profile has not been reported.Methods
We have performed a time course analysis of the characteristic molecular mediators and cellular influx in the bronchoalveolar lavage (BAL) and lung in order to define the pulmonary inflammatory response to inhaled HDM extract. Mice were exposed five times a week to soluble HDM extract for 3 weeks. Lung function was measured in groups of mice at intervals following the final HDM challenge. Recruitment of inflammatory cells and inflammatory mediator production was then assessed in BAL and lungs of individual mice.Results
We found that Th2 cytokines were significantly increased in BAL and lung after HDM challenge from as early as 2 h post‐final challenge. The levels of cytokines and chemokines correlated with the influx of eosinophils and Th2 cells to the different compartments of the lung. However, the production of key cytokines such as IL‐4, IL‐5 and IL‐13 preceded the increase in airways resistance.Conclusion
Inhaled HDM challenge induces a classical Th2 inflammatory mediator profile in the BAL and lung. These data are important for studies determining the efficacy of novel treatment strategies for allergic airways disease.
Changes in asthma‐like responses after extended removal from exposure to trimellitic anhydride in the Brown Norway rat model
Authors: Zhang X. D. , Hubbs A. F. , Siegel P. D. 
Published: June 2009

SummaryBackground
Organic acid anhydride‐induced occupational asthma is considered to be IgE‐mediated. Airway and skin exposure are the two main routes of sensitization in the work place. Recently we developed an allergic asthmatic Brown Norway rat model sensitized by dermal exposure to trimellitic anhydride (TMA) using an occlusion patch application.Objectives
The objectives of this study were (1) to develop a model of non‐occluded dermal exposure leading to allergic sensitization and (2) to examine the effect of extended removal from exposure on persistence of both specific IgE and TMA aerosol‐induced airway responses in this model.Methods
TMA powder (4 or 40 mg) was applied, unoccluded, to the skin of rats for 4 h, once/week for 4 weeks. Rats were given a 10‐min aerosol challenge to 40 mg/m3 TMA 2 weeks after the last dermal exposure (day 35). Another group was challenged on day 35 and again 18–24 months later. Respiratory enhanced pause (Penh), pulmonary histopathology and inflammation and specific IgE titres were measured.Results
Rats produced dose‐dependent specific IgE titres after exposure and developed early‐phase (EAR) and late‐phase airway responses (LAR) after airway challenge to TMA aerosol as well as airway eosinophilic inflammation. Specific airway responses were still manifested after a second TMA airway challenge given 18–24 months following the initial airway challenge. While persistent, airway inflammation, specific IgE and EAR were significantly attenuated following the second TMA challenge. LAR remained robust at 18–24 months and was not significantly different from the response on day 35.Conclusions
These results demonstrate the persistence of chemical sensitization and further suggest that IgE is not essential for LAR.
Factors determining the remission of microprolactinomas after dopamine agonist withdrawal
Authors: Huda M. S. B. , Athauda N. B. , Teh M. M. , Carroll P. V. , Powrie J. K. 
Published: June 2009

SummaryBackground  Withdrawal of dopamine agonist (DA) therapy in the management of microprolactinoma is common practice, but it is unclear which patients are likely to attain long‐term remission.Objective  To identify predictive factors for long‐term remission.Design  Prospective cohort study.Patients  Forty subjects (39 female, aged 24–60 years) with microprolactinoma; all had been normoprolactinaemic on DA therapy for at least 2 years [mean duration of therapy 9 years (range 2–27)].Measurements  A pituitary magnetic resonance imaging (MRI) was performed on 36 (90%) subjects before DA withdrawal. Relapse was defined as prolactin greater than 480 mIU/l (22·8 μg/l) on two occasions.Results  Nine out of 40 (22·5%) subjects were normoprolactinaemic 12 months after DA withdrawal. Amongst the relapse group, 24 of 31 subjects (79·4%) had already relapsed at 3 months. Normalization of MRI prior to DA withdrawal (P = 0·0006) and longer duration of DA treatment (P = 0·032) were significant predictors of remission. Age, pre‐treatment prolactin, nadir prolactin, previous failure of DA withdrawal, pregnancy, dose and type of DA were not significant predictors of remission. The nine patients who were in remission at 12 months were then followed up for 58·0 ± 5·8 months; all remained in remission.Conclusions  As many as 22·5% of subjects with microprolactinoma remained normoprolactinaemic 12 months after DA withdrawal and these subjects stayed in remission for up to 5 years. Significant predictive factors were normalization of MRI prior to discontinuation, and duration of DA treatment. Our findings support intermittent DA withdrawal after a period of normoprolactinaemia, particularly where MRI appearances have normalized.
The adipokine zinc‐α2‐glycoprotein (ZAG) is downregulated with fat mass expansion in obesity
Authors: Mracek T. , Ding Q. , Tzanavari T. , Kos K. , Pinkney J. , Wilding J. , Trayhurn P. , Bing C. 
Published: June 2009

SummaryIntroduction  Zinc‐α2‐glycoprotein (ZAG) is a novel adipokine, which may act locally to influence adipocyte metabolism. This study assessed the effect of increased adiposity on ZAG expression in adipose tissue in human subjects. The study also examined the association between ZAG and adiponectin expression in human adipose tissue, and whether ZAG modulates adiponectin secretion by human adipocytes.Methods  Adipose tissue (visceral and subcutaneous) was collected from human subjects with a wide range of BMIs. Human Simpson‐Golabi‐Behmel syndrome (SGBS) adipocytes were used for in vitro studies. ZAG mRNA levels were quantified by real‐time PCR and protein by Western blotting.Results  In human subjects, ZAG mRNA level was negatively correlated with BMI (r = −0·61, P < 0·001, n = 23, visceral; r = −0·6, P < 0·05, n = 14, subcutaneous) and fat mass (r = −0·62, P < 0·01, visceral; r = −0·6, P < 0·05, subcutaneous). Negative associations were also found between ZAG mRNA and insulin resistance parameters including plasma insulin (r = −0·65, P < 0·001, visceral; r = −0·55, P < 0·05, subcutaneous) and homeostasis model of insulin resistance (HOMA‐IR) (r = −0·65, P < 0·001, visceral; r = −0·52, P = 0·055, subcutaneous), and C reactive protein (CRP) (r = −0·46, P < 0·05, visceral; r = −0·53, P < 0·05, subcutaneous). However, ZAG mRNA was positively correlated with adiponectin (r = 0·5, P < 0·05, visceral; r = 0·82, P < 0·001, subcutaneous) but negatively associated with leptin mRNA (r = −0·42, P < 0·05, visceral; r = −0·54, P < 0·05, subcutaneous). ZAG secretion by differentiated human adipocytes was abundant. Addition of recombinant ZAG stimulated adiponectin release from human adipocytes.Conclusion  ZAG gene expression in adipose tissue is downregulated with increased adiposity and circulating insulin. ZAG mRNA is positively correlated with adiponectin mRNA, and ZAG enhances adiponectin production by human adipocytes. We suggest that ZAG is linked to obesity and obesity‐related insulin resistance.
Leptin secretion rate increases with higher CAG repeat number in Huntington’s disease patients
Authors: Ahmad Aziz N. , Pijl Hanno , Frölich Marijke , Maurits van der Graaf A.W. , Roelfsema Ferdinand , Roos Raymund A.C. 
Published: June 2009

SummaryBackground  Huntington’s disease (HD) is a hereditary neurodegenerative disorder caused by an increased number of CAG repeats in the huntingtin gene. A hallmark of HD is unintended weight loss, the cause of which is unknown.Objective  To perform a detailed analysis of adipose tissue function in HD patients as abnormal fat tissue function could contribute to the weight loss.Design, setting and participants  In a clinical research laboratory, 24‐h plasma concentrations of leptin, adiponectin and resistin were studied in nine early‐stage, medication‐free HD patients and nine age‐, gender‐ and body mass index (BMI)‐matched controls.Measurements  Leptin was measured every 20 min whereas adiponectin and resistin were measured hourly. Autodeconvolution and cosinor regression were applied to quantify secretion characteristics of leptin and diurnal variations in leptin, adiponectin and resistin levels.Results  Plasma levels and diurnal rhythmicity of leptin, adiponectin and resistin were not significantly different between HD patients and controls. However, although leptin production increased with higher BMI and fat mass in controls, no such relation was present in HD patients. Moreover, when corrected for fat mass, mean plasma leptin concentration as well as basal, pulsatile and total secretion rates increased with the size of the CAG repeat mutation (r = +0·72 to r = +0·80; all P < 0·05). Both higher pulsatile leptin secretion and higher mean adiponectin levels were associated with a greater degree of motor and functional impairment in HD patients.Conclusions  CAG‐repeat size‐dependent interference of the HD mutation with adipose tissue function may contribute to weight loss in HD patients.
How should the patient with multiple endocrine neoplasia type 1 (MEN 1) be followed?
Authors: Burgess John 
Published: June 2009

SummaryMultiple endocrine neoplasia type 1 (MEN 1) is a complex multi‐system disease manifesting a diverse range of primary and secondary metabolic and neoplastic disorders. It is possible to improve patient prognosis by early disease detection and treatment. Regular biochemical and radiological screening for parathyroid, gastro‐enteropancreatic, pituitary, intrathorasic and adrenal lesions forms the basis of surveillance. The likelihood of adverse sequelea such as renal and bone disease resulting from hyperparathyroidism, severe peptic ulceration and gastric carcinoidosis secondary to hypergastrinaemia can be ameliorated by early detection and management.
Suppression of inflammatory responses by celastrol, a quinone methide triterpenoid isolated fromCelastrus regelii
Authors: Kim D. H. , Shin E. K. , Kim Y. H. , Lee B. W. , Jun J.‐G. , Park J. H. Y. , Kim J.‐K. 
Published: June 2009

AbstractBackground Celastrol, a quinone methide triterpenoid isolated from theCelastraceaefamily, exhibits various biological properties, including chemopreventive, antioxidant and neuroprotective effects. In this study, we showed that celastrol inhibits inflammatory reactions in macrophages and protects mice from skin inflammation.Materials and methods Anti‐inflammatory effects of celastrol (0–1 μM) were examined in lipopolysaccharide (LPS)‐stimulated RAW 264·7 macrophages. To investigate the effects of celastrol (0–50 μg per mice)in vivo, activation of myeloperoxidase (MPO) and histological assessment were examined in the 12‐O‐tetradecanoyl‐phorbol‐13‐acetate (TPA)‐induced mouse ear oedema model.Results Ourin vitroexperiments showed that celastrol suppressed not only LPS‐stimulated generation of nitric oxide and prostaglandin E2, but also expression of inducible nitric oxide synthase and cyclooxygenase‐2 in RAW264·7 cells. Similarly, celastrol inhibited LPS‐induced production of inflammatory cytokines, including tumour necrosis factor‐α and interleukin‐6. In an animal model, celastrol protected mice from TPA‐induced ear oedema, possibly by inhibiting MPO activity and production of inflammatory cytokines.Conclusions Our data suggest that celastrol inhibits the production of inflammatory mediators and is a potential target for the treatment of various inflammatory diseases.
Assessment of arsenic availability to roots in contaminated Tuscany soils by a diffusion gradient in thin films (DGT) method and uptake by Pteris vittata and Agrostis capillaris
Authors: Cattani I. , Capri E. , Boccelli R. , Del Re A.A.M. 
Published: June 2009

SummaryA laboratory study was conducted to evaluate the availability of arsenic (As) to roots in nine soils from five fields in Tuscany (Italy). Concentrations of As in soils range from 200 to 1200 mg kg−1 as a result of human activities and natural deposition. In a first stage, potentially root‐available As and the risk of crop uptake were estimated using the diffusion gradient in thin films (DGT) technique. In a second stage, a glasshouse experiment was performed to compare As depletion in the rhizosphere by the hyperaccumulator Pteris vittata (ladder brake), and by the test plant Agrostis capillaris (colonial bentgrass). In this stage, DGT results were supported by a sequential extraction procedure. The main objectives were to study the root availability of As in old, contaminated soils and the modification of the available pool size over time. The phytoextraction efficiency of Pteris vittata as applied to this case study was also investigated. In all samples, concentrations of total and potentially root‐available As in soil solution were small compared with total As in soil (approximately 0.0003–0.03%, corresponding to 3.5–350 μg l−1, respectively). There was also little re‐supply of As from the solid phase to the soil solution. In the rhizosphere, despite uptake by Pteris and Agrostis, total and root available As in solution were sustained over time. It appeared that plants induced a re‐supply of As from the solid phase. Despite the uptake and translocation of As by Pteris (50.7 mg kg−1 and 6.6 mg As kg−1 in fronds and roots, respectively) together with plant biomass (17.2 g per plant), the success of phytoextraction appears unlikely. The results obtained demonstrated the sensitivity of DGT to root‐induced changes in soil and the suitability of the technique as an easy‐to‐use tool to predict assimilation by plants.
Shrinkage behaviour of transiently‐ and constantly‐loaded soils and its consequences for soil moisture release
Authors: Peng X. , Dörner J. , Zhao Y. , Horn R. 
Published: June 2009

SummarySoils under loaded conditions may have different shrinkage behaviour from that of load‐free soils. In this study, we applied two kinds of mechanical stress (σ) on repacked homogeneous soil samples: transient and constant stresses, simulating the traffic load during tillage and the overburden pressure, respectively. Three transient stresses were applied on the soil surface with 150, 400 and 1400 kPa, while the constant stresses ranged from 1.8, 3.8, 5.5, to 7.3 kPa. We hypothesized that the two stresses play different roles in soil shrinkage behaviour as depicted by void ratio (e) and moisture ratio (ϑ), as compared with load‐free soil. Thus, our aim was to build up the relationship between e, ϑ and σ. For a swelling soil, total pores can be divided into rigid and non‐rigid components according to their swelling and shrinkage capacity relative to soil moisture. The non‐rigid pores compacted by the transient stress can be regained in the subsequent wetting at load‐free conditions, whereas the compacted rigid pores do not recover. The reduction in rigid pores does not alter the soil pore shrinkage capacity. The shrinkage curves of transiently‐loaded soils are therefore parallel to each other with an identical coefficient of linear extensibility (COLE) and the same shrinkage slope, although their structural shrinkage phase narrows with an increase of stress. However, the constant stress compresses non‐rigid pores readily through suppressing their swelling capacity during wetting as well as compacting rigid pores. If the change of rigid pores is negligible, the shrinkage curves of constantly‐loaded soils converge at the zero shrinkage or the dry‐end point with the load‐free soil shrinkage. If the reductions of rigid and non‐rigid pores are both considered, the soil shrinkage combines the part of parallel shrinkage derived from the reduced rigid pores and the intersected shrinkage resulted from the altered non‐rigid pores. On the basis of different shrinkage behaviours resulting from the two mechanical stresses, we propose numerical formulae to illustrate a series of curves for the e‐ϑ‐σ relationship. The different changes in rigid and non‐rigid pores cause soil water release differently.