bluuebunny/crossref_metadata_2025_split huggingface dataset:
A pharmacokinetic model of filgrastim and pegfilgrastim application in normal mice and those with cyclophosphamide‐induced granulocytopaenia
Authors: Scholz M. , Ackermann M. , Engel C. , Emmrich F. , Loeffler M. , Kamprad M. 
Published: August 2009

AbstractObjectives: Recombinant human granulocyte colony‐stimulating factor (rhG‐CSF) is widely used as treatment for granulocytopaenia during cytotoxic chemotherapy; however, optimal scheduling of this pharmaceutical is unknown. Biomathematical models can help to pre‐select optimal application schedules but precise pharmacokinetic properties of the pharmaceuticals are required at first. In this study, we have aimed to construct a pharmacokinetic model of G‐CSF derivatives filgrastim and pegfilgrastim in mice.Methods: Healthy CD‐1 mice and those with cyclophosphamide‐induced granulocytopaenia were studied after administration of filgrastim and pegfilgrastim in different dosing and timing schedules. Close meshed time series of granulocytes and G‐CSF plasma concentrations were determined. An ordinary differential equations model of pharmacokinetics was constructed on the basis of known mechanisms of drug distribution and degradation.Results: Predictions of the model fit well with all experimental data for both filgrastim and pegfilgrastim. We obtained a unique parameter setting for all experimental scenarios. Differences in pharmacokinetics between filgrastim and pegfilgrastim can be explained by different estimates of model parameters rather than by different model mechanisms. Parameter estimates with respect to distribution and clearance of the drug derivatives are in agreement with qualitative experimental results.Conclusion: Dynamics of filgrastim and pegfilgrastim plasma levels can be explained by the same pharmacokinetic model but different model parameters. Beause of a strong clearance mechanism mediated by granulocytes, granulocytotic and granulocytopaenic conditions must be studied simultaneously to construct a reliable model. The pharmacokinetic model will be extended to a murine model of granulopoiesis under chemotherapy and G‐CSF application.
Allergen‐specific antibody and cytokine responses, mast cell reactivity and intestinal permeability upon oral challenge of sensitized and tolerized mice
Authors: Perrier C. , Thierry A.‐C. , Mercenier A. , Corthésy B. 
Published: August 2009

SummaryBackground
Food allergy has reached an epidemic level in westernized countries and although central mechanisms have been described, the variability associated with genetic diversity underscores the still unresolved complexity of these disorders.Objective
To develop models of food allergy and oral tolerance, both strictly induced by the intestinal route, and to compare antigen‐specific responses.Methods
BALB/c mice were mucosally sensitized to ovalbumin (OVA) in the presence of the mucosal adjuvant cholera toxin, or tolerized by intra‐gastric administrations of OVA alone. Antibody titres and cytokines were determined by ELISA, and allergic status was determined through several physiologic parameters including decline in temperature, diarrhoea, mast cell degranulation and intestinal permeability.Results
OVA‐specific antibodies (IgE, IgGs and IgA in serum and feces) were produced in sensitized mice exclusively. Upon intra‐gastric challenge with OVA, sensitized mice developed anaphylactic reactions associated with a decline of temperature, diarrhoea, degranulation of mast cells, which were only moderately recruited in the small intestine, and increased intestinal permeability. Cytokines produced by immune cells from sensitized mice included T‐helper type 2 cytokines (IL‐5, IL‐13), but also IL‐10, IFN‐γ and IL‐17. In contrast, all markers of allergy were totally absent in tolerized animals, and yet the latter were protected from subsequent sensitization, demonstrating that oral tolerance took place efficiently.Conclusion
This work allows for the first time an appropriate comparison between sensitized and tolerized BALB/c mice towards OVA. It highlights important differences from other models of allergy, and thus questions some of the generally accepted notions of allergic reactions, such as the protective role of IFN‐γ, the importance of antigen‐specific secretory IgA and the role of mucosal mast cells in intestinal anaphylaxis. In addition, it suggests that IL‐17 might be an effector cytokine in food allergy. Finally, it demonstrates that intestinal permeability towards the allergen is increased during challenge. Cite this as: C. Perrier, A.‐C. Thierry, A. Mercenier and B. Corthésy, Clinical & Experimental Allergy, 2010 (40) 153–162.
Digested Ara h 1 has sensitizing capacity in Brown Norway rats
Authors: Bøgh K. L. , Kroghsbo S. , Dahl L. , Rigby N. M. , Barkholt V. , Mills E. N. C. , Madsen C. B. 
Published: August 2009

SummaryBackground
Food allergies are a public health issue of growing concern, with peanuts in particular being associated with severe reactions. The peanut allergen, Ara h 1, belongs to the cupin plant food allergen family, which, unlike other structural families, appears to be broken down rapidly following gastrointestinal digestion.Objective
Using Ara h 1 as a model allergen, the ability of digested protein to sensitize has been investigated.Methods
Ara h 1 was purified from whole roasted peanuts. Intact Ara h 1 was digested in an in vitro model, simulating the human gastrointestinal digestion process. Digestion products were analysed for peptide sizes and their ability to aggregate. Brown Norway (BN) rats, used as an animal model, were immunized with purified intact Ara h 1 or the gastrointestinal digestion products thereof. The sensitizing capacity was evaluated by analyses of specific antibody (IgG1, IgG2a and IgE) responses and ability to trigger mediator release of rat basophilic leukaemia (RBL)‐2H3 cells.Results
The present study showed that Ara h 1 was broken down, resulting in peptide fragments of sizes <2.0 kDa, of which approximately 50% was in aggregated complexes of Mr up to 20 kDa. Ara h 1 digesta were shown to have sensitizing capacity in BN rats, being capable of inducing specific IgG and IgE antibodies. The IgE response was functional, having the capacity to induce specific degranulation of RBL cells.Conclusion
From this study, it can be concluded that lability of a food allergen to gastrointestinal digestion does not necessarily abrogate its allergenic sensitizing potential.
Comparison of skin prick tests with specific serum immunoglobulin E in the diagnosis of fungal sensitization in patients with severe asthma
Authors: O'Driscoll B. R. , Powell G. , Chew F. , Niven R. M. , Miles J. F. , Vyas A. , Denning D. W. 
Published: August 2009

SummaryBackground
It has been shown that patients with allergic bronchopulmonary aspergillosis (ABPA) and patients with severe asthma with fungal sensitization (SAFS) can benefit from antifungal therapy. It is not known whether allergy skin prick tests (SPT) or specific IgE tests are more sensitive in the identification of patients who are sensitized to fungi and who are therefore candidates for antifungal therapy.Objectives
To compare SPT and specific serum IgE tests for fungal sensitization in patients with severe asthma.Methods
We have undertaken SPT and specific serum IgE tests to six fungi (Aspergillus fumigatus, Candida albicans, Penicillium notatum, Cladosporium herbarum, Alternaria alternata and Botrytis cineria) and specific serum IgE test for Trichophyton in 121 patients with severe asthma (British Thoracic Society/SIGN steps 4 and 5).Results
Sixty‐six percent of patients were sensitized to one or more fungi based on SPT and/or specific serum IgE results. Positivity to SPT and/or specific serum IgE was as follows: A. fumigatus 45%, C. albicans 36%, P. notatum 29%, C. herbarum 24%, A. alternata 22%, B. cineria 18%, Trichophyton 17% (specific serum IgE only). Concordance between the tests was 77% overall but only 14–56% for individual fungi. Twenty‐nine (24%) patients were sensitized to a single fungus and seven (6%) were sensitized to all seven fungal species. Fifty percent of patients were sensitized to fungal and non‐fungal extracts, 21% were sensitized only to non‐fungal extracts, 16% were sensitized only to fungal extracts and 13% had no positive tests.Conclusion
This study is consistent with previous reports that fungal sensitization is common in patients with severe asthma. At present, it remains necessary to undertake both SPT and specific serum IgE testing to identify all cases of fungal sensitization. This may be important in the identification of patients with ABPA and SAFS who may benefit from antifungal therapy.
Basophil responsiveness in patients with insect sting allergies and negative venom‐specific immunoglobulin E and skin prick test results
Authors: Korosec P. , Erzen R. , Silar M. , Bajrovic N. , Kopac P. , Kosnik M. 
Published: August 2009

SummaryBackground
Current guidelines do not adequately address the question of how best to manage patients with a convincing history of insect allergy, but negative venom‐specific IgE and skin test results.Methods
Forty‐seven patients out of a total of 1219 (4%), with a positive history of sting allergy, were recruited over a period of 4.5 years. All recruited patients had a convincing history of a severe or a life‐threatening anaphylactic reaction of Mueller grade II–IV (median grade III) after Hymenoptera sting, but negative venom‐specific IgE and skin prick test results. Diagnostic work‐up was prospectively followed by the CD63 basophil activation test and by intradermal skin testing. A control group of 25 subjects was also assessed.Results
Thirty‐five out of 47 (75%) patients demonstrated a positive basophil CD63 response after stimulation with bee and/or wasp venom. Intradermal venom skin tests were performed for 37 patients, 17 (46%) of whom showed positive results. Out of 20 patients who demonstrated negative intradermal test results, 12 patients showed a positive CD63 response (60%). In contrast, out of 9 patients who showed a negative CD63 response, only one was detected by intradermal testing (11%). In the control group, only two out of 25 (4%) subjects displayed a positive basophil response and/or intradermal test.Conclusion
Here we show that, in complex cases with inconclusive diagnostic results, the CD63 activation test could be particularly useful and more sensitive than intradermal skin testing.
Calcineurin deficiency decreases inflammatory lesions in transforming growth factor β1-deficient mice
Authors: Bommireddy R , Bueno O F , Martin J , Ormsby I , Chen H , Gard C , Molkentin J D , Boivin G P , Babcock G F , Doetschman T 
Published: August 2009

SummaryTransforming growth factor (TGF) β1) is an immunoregulatory cytokine involved in self-tolerance and lymphocyte homeostasis. Tgfb1 knock-out (KO) mice develop severe multi-focal autoimmune inflammatory lesions due to [Ca2+]i deregulation in T cells, and die within 3 weeks after birth. Because the calcineurin inhibitor FK506 inhibits the hyperresponsiveness of Tgfb1−/− thymocytes, and because calcineurin Aβ (CNAβ)-deficient mice do not reject allogenic tumours, we have generated Tgfb1−/−Cnab−/− mice to address whether CNAβ deficiency prevents T cell activation and inflammation in Tgfb1−/− mice. Here we show that in Tgfb1−/−Cnab−/− mice inflammation is reduced significantly relative to that in Tgfb1−/− mice. However, both CD4+ and CD8+ T cells in double knock-out (DKO) mice are activated, as revealed by up-regulation of CD11a lymphocyte function-associated antigen-1 (LFA-1), CD44 and CD69 and down-regulation of CD62L. These data suggest that deficiency of CNAβ decreases inflammatory lesions but does not prevent activation of autoreactive T cells. Also Tgfb1−/− T cells can undergo activation in the absence of CNAβ, probably by using the other isoform of calcineurin (CNAα) in a compensatory manner. CNAβ-deficient T cells undergo spontaneous activation in vivo and are activated upon anti-T cell receptor stimulation in vitro. Understanding the role of calcineurin in T cell regulation should open up new therapeutic opportunities for inflammation and cancer.
Lateral velocity variation related correction in asymptotic true‐amplitude one‐way propagators
Authors: Cao Jun , Wu Ru‐Shan 
Published: August 2009

ABSTRACTIt was mathematically proved that the asymptotic true‐amplitude one‐way wave equation could provide the same amplitude as the full‐wave equation in heterogeneous lossless media in the sense of high‐frequency asymptotics. Much work has been done on the vertical velocity variation related amplitude correction term but the lateral velocity variation related term has not received much attention, even being excluded in some asymptotic true‐amplitude one‐way propagator formulations. Here we analyse the effects of different amplitude correction terms in the asymptotic true‐amplitude one‐way propagator, especially the effect related to the lateral velocity variation, by comparing the wavefield amplitude from the one‐way propagator with that from full‐wave modelling. We derive a dual‐domain wide‐angle screen type asymptotic true‐amplitude one‐way propagator and evaluate two implementations of the amplitude correction. Numerical examples show that the lateral velocity variation related correction term can play a significant role in the asymptotic true‐amplitude one‐way propagator. Optimization of the expansion coefficients in the asymptotic true‐amplitude one‐way propagator can improve both the amplitude and phase accuracy for wide‐angle waves.
Contrasting phylogeographical patterns for springtails reflect different evolutionary histories between the Antarctic Peninsula and continental Antarctica
Authors: McGaughran Angela , Torricelli Giulia , Carapelli Antonio , Frati Francesco , Stevens Mark I. , Convey Peter , Hogg Ian D. 
Published: August 2009

AbstractAim We examined the genetic structure among populations and regions for the springtailsCryptopygus antarcticus antarcticusandGomphiocephalus hodgsoni(Collembola) to identify potential historical refugia and subsequent colonization routes, and to examine population growth/expansion and relative ages of population divergence.Location Antarctic Peninsula forC. a. antarcticus; Antarctic continent (southern Victoria Land) forG. hodgsoni.Methods Samples were collected from 24 and 28 locations across the Antarctic Peninsula and southern Victoria Land regions forC. a. antarcticusandG. hodgsoni, respectively. We used population genetic, demographic and nested clade analyses based on mitochondrial DNA (cytochromecoxidase subunit I and subunit II).Results Both species were found to have population structures compatible with the presence of historical glacial refugia on Pleistocene (2 Ma–present) time‐scales, followed by post‐glacial expansion generating contemporary geographically isolated populations. However,G. hodgsonipopulations were characterized by a fragmented pattern with several ‘phylogroups’ (likely ancestral haplotypes present in high frequency) retaining strong ancestral linkages among present‐day populations. Conversely,C. a. antarcticushad an excess of rare haplotypes with a much reduced volume of ancestral lineages, possibly indicating historical founder/bottleneck events and widespread expansion.Main conclusions We infer that these differences reflect distinct evolutionary histories in each locality despite the resident species having similar life‐history characteristics. We suggest that this has predominantly been influenced by variation in the success of colonization events as a result of intrinsic historical glaciological differences between the Antarctic Peninsula and continental Antarctic environments.
Explosive evolution of an ancient group of Cyphophthalmi (Arachnida: Opiliones) in the Balkan Peninsula
Authors: Murienne Jérôme , Karaman Ivo , Giribet Gonzalo 
Published: August 2009

AbstractAim  To investigate the phylogeny of the genus Cyphophthalmus in the Balkan Peninsula and to test the current recognition of ‘phyletic lines’ and phylogenetic groups proposed in previous studies in order to elucidate the biogeographical history of the region.Location  Europe, Balkan Peninsula, Adria microplate.Methods  Two mitochondrial (cytochrome c oxidase subunit I and 16S rRNA) and two nuclear (28S rRNA and 18S rRNA) markers were used to infer the phylogenetic history of the group. Molecular dating with relaxed molecular clocks was used to elucidate the relative time of diversification within the genus Cyphophthalmus and its constituent lineages.Results  Our analyses confirm the monophyly of the genus Cyphophthalmus, and that of the Aegean and gjorgjevici lineages, whereas the ‘Dinaric lineage’ appears paraphyletic.Main conclusions  We show that the genus Cyphophthalmus is an old endemic from the Balkan biogeographical region, which gave origin to at least three main lineages. Those lineages have diversified within overlapping ranges. According to our molecular dating, they have also diversified within the same timeframe. The Dinaric Alps, although presenting a large number of species, cannot be inferred as the centre of origin of the group. Instead, the biogeographical evolution of the genus could be related to the palaeogeographic history of the Adria microplate.
Phylogeography of the Guinea multimammate mouse (Mastomys erythroleucus): a case study for Sahelian species in West Africa
Authors: Brouat Carine , Tatard Caroline , Bâ Khalilou , Cosson Jean‐François , Dobigny Gauthier , Fichet‐Calvet Elisabeth , Granjon Laurent , Lecompte Emilie , Loiseau Anne , Mouline Karine , Piry Sylvain , Duplantier Jean‐Marc 
Published: August 2009

AbstractAim  To investigate the phylogeographical structure of the Guinea multimammate mouse, Mastomys erythroleucus (Temminck, 1853), a widespread murid rodent in sub‐Saharan (Sahel and Sudan) savannas, for a better understanding of the impacts of geographical and historical factors on the evolutionary history of this species, in the context of the growing database of phylogeographical studies of African savanna mammal species.Location  Sahel and Sudan savannas, Africa.Methods  We sequenced the whole cytochrome b gene in 211 individuals from 59 localities distributed from Senegal to Ethiopia. Sequence data were analysed using both phylogenetic (several rooted tree‐construction methods, median‐joining networks) and population genetic methods (spatial analyses of molecular variance, mismatch distributions).Results  Haplotypes were distributed into four major monophyletic groups corresponding to distinct geographical regions across a west–east axis. Diversification events were estimated to have occurred between 1.16 and 0.18 Ma.Main conclusions  Vicariance events related to the fragmentation of savanna habitats during the Pleistocene era may explain the phylogeographical patterns observed. Genetic structure was consistent with a role of major Sahelian rivers as significant barriers to west–east dispersal. Recent demographic expansions probably occurred during arid phases of the Holocene with the southward expansion of savannas.
How many buffalo does it take to change a savanna? A response to Bowman et al. (2008)
Authors: Petty Aaron M. , Werner Patricia A. 
Published: August 2009

AbstractBowman et al. (Journal of Biogeography, 2008, 35, 1976–1988) aimed to explain observed increases in woody cover on floodplains and savannas of Kakadu National Park using estimates of buffalo (Bubalus bubalis) density as a causal variable. They found that buffalo were a minor model variable and concluded that buffalo are ‘not a major driver of floodplain and eucalypt dynamics’. However, the authors mislabelled the historical density of buffalo on their site, citing a period as high density instead of low density. Further, their results were not contextualized within the substantial body of scientific and historical evidence of the buffalo’s strong influence on vegetation in Kakadu. The authors instead postulated three unanalysed drivers of observed patterns of change: fire regime, rainfall and atmospheric CO2. We suggest that further analyses of change in woody vegetation should make use of accurate historical records of grazers as well as available data sets on fire history.
Failure to detect deaf‐blindness in a population of people with intellectual disability
Authors: Fellinger J. , Holzinger D. , Dirmhirn A. , Van Dijk J. , Goldberg D. 
Published: August 2009

AbstractBackground Early identification of deaf‐blindness is essential to ensure appropriate management. Previous studies indicate that deaf‐blindness is often missed. We aim to discover the extent to which deaf‐blindness in people with intellectual disability (ID) is undiagnosed.Method A survey was made of the 253 residents of an institute offering residential and occupational facilities for people with IDs. Data are included for the 224 individuals who were able to complete both auditory and visual assessments. Otoacoustic emissions were used to screen for hearing impairment; those who did not pass were assessed by behavioural audiometry. Visual acuity was assessed with one of the following: EH‐Optotypes, LH‐Optotypes, Teller Acuity Cards, Cardiff Acuity Cards or the Stycar Ball Vision Test.Results Prior to the study hearing impairment had been diagnosed in 12.5% of the 224 subjects, and visual impairment in 17%. Upon completion of the study these figures rose to 46% and 38.4% respectively. Deaf‐blindness was diagnosed in 3.6% of the subjects before, and in 21.4% after, the study. Most (87.5%) of the deaf‐blind individuals had profound ID.Conclusion Deaf‐blindness is most often not identified either by standard medical screening or by care staff. Individuals with this disability, however, require provision of special kinds of care. Four categories of deaf‐blindness are proposed, according to the severity of sensory impairment in each modality. The tests used in this study are non‐invasive and are appropriate for individuals with ID and children. Early and periodic screening for visual and hearing impairment in individuals with ID is recommended.
Dysfunctional beliefs and attitudes about sleep in children
Authors: GREGORY ALICE M. , COX JENNY , CRAWFORD MEGAN R. , HOLLAND JESSICA , HARAVEY ALLISON G. ,   The Steps Team
Published: August 2009

SummaryThe objective of the study was to determine whether associations between dysfunctional beliefs and attitudes about sleep and sleep disturbance are evident in children. Cross‐sectional data were collected from 123 children aged 8–10 years (49% boys). The participants came from ethnically diverse backgrounds from two inner‐city schools in London, UK. Children completed the Sleep Self‐Report (SSR) and the Dysfunctional Beliefs and Attitudes about Sleep (DBAS) questionnaire (which was adapted for use with children). Parents completed the Child Sleep Habits Questionnaire (CSHQ). The total DBAS score was associated with sleep disturbances defined as total SSR score (β = 0.40, P < 0.001, r2 = 0.15), the SSR insomnia items (β = 0.29, P < 0.01, r2 = 0.08) and the total CSHQ score (β = 0.22, P < 0.05, r2 = 0.04). Some dysfunctional beliefs about sleep predicted sleep disturbance to a greater extent than others. For example, when controlling for the other DBAS subscales, the ‘control and predictability of sleep’ subscale, but not the ‘sleep requirements expectations’ subscale, predicted total SSR score and SSR insomnia items. Given this preliminary evidence that dysfunctional beliefs and attitudes about sleep appear to be associated with sleep difficulties in children, future work is needed to further developmentally adapt a version of the DBAS appropriate for use with children.
Plexiform neurofibromas in neurofibromatosis type 1
Authors: Sehgal Virendra N. , Srivastava Govind , Aggarwal Ashok K. , Oberai Rakesh 
Published: August 2009

AbstractPlexiform neurofibroma developing in neurofibromatosis type 1 is a fascinating overture whereby diagnosis is primarily based on clinical characteristics, the details of which are outlined. Nonetheless, it is imperative to establish a clear‐cut clinical status vis‐á‐vis the adjoining tissues. Magnetic resonance imaging (MRI) may provide an additional supplement to the diagnosis and an aid to further management of the condition.